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Dr Erin C. Berthold from Planted in Science Consulting LLC discusses the uses and perceptions of botanical medicines, emphasizing the necessity for coordinated global efforts to understand and regulate these substances to ensure their safe integration into healthcare

Botanicals have long been used in traditional medicine practices. In developing nations, particularly in Africa, up to 80% of the population relies on traditional medicine as their primary source of care. ⁽¹⁾ This historical use of botanicals as medicines also profoundly shaped modern pharmacology, with botanical compounds serving as frameworks or direct sources for roughly one-third of all drugs approved by the U.S. Food and Drug Administration (FDA). ⁽²⁾

The growing demand for ‘natural’ remedies

Today, however, the landscape of botanical medicine is undergoing a significant transformation. A surge in wellness trends and a growing consumer preference for ‘natural’ products has led to a boom in their use in developed countries. This shift, combined with a steady increase in the use of prescription medications, is creating potential for botanical-drug interactions. Sales data show that from 2017 to 2023, there was an increase of over $4 billion in sales of botanical supplements in the United States, while at the same time, pharmaceutical sales grew by over $100 billion (Figure 1).

Safety concerns surrounding botanical supplementation

A pervasive misconception about botanicals is that they are inherently safer than pharmaceuticals. This belief is based on the long history of traditional use of plant medicines, the accessibility of botanical supplements, and a bias against ‘synthetic’ chemicals. This leads many individuals to use botanicals concurrently with their prescription medications without informing their healthcare providers. This co-administration of botanicals and pharmaceuticals is not a niche behavior. A survey of US participants revealed that 38% used herbals alongside prescription drugs, with a concerning prevalence among adults over 70 – a demographic particularly vulnerable to adverse effects from polypharmacy due to altered metabolism. ⁽³⁾ Compounding this issue, as many as two-thirds of individuals do not disclose their botanical supplement use to their physicians, creating a significant information gap in patient care. ⁽⁴⁾

While the pharmaceutical industry is held to a rigorous standard, requiring extensive pre-market research into drug-drug and food-drug interactions, botanical supplements are often governed by different, far less stringent rules, and issues are often only recognized in post-market surveillance. This regulatory disparity leads to a marketplace where botanical products lack standardized potency, clear instructions, and any meaningful data on their potential interactions with prescription medications.

Botanicals are chemically complex, containing a multitude of compounds that may alter the effects of a co-administered drug. In some cases, they may increase the effects of a prescribed medication, leading to adverse events, a particularly dangerous scenario for drugs with a narrow therapeutic window. Conversely, they may decrease the efficacy of a drug, which can be life-threatening or life-changing when the medication is for a critical condition like cardiac disease or contraception. ⁽⁵⁾

The clinical consequences of this regulatory gap and public misconception are becoming increasingly visible. One trend is the rising incidence of drug-induced liver injury (DILI) due to herbal and dietary supplements. While DILI from botanicals is often idiosyncratic, its prevalence is growing. Data from the Drug-Induced Liver Injury Network (DILIN) shows that the percentage of DILI cases attributed to herbal and dietary supplements soared from 7% in 2004-2005 to 20% in 2013-2014. ⁽⁶⁾

Botanicals and research gaps

Despite the growing prevalence and clear risks, research into botanical-drug interactions has not kept pace. In fact, a search of the biomedical database PubMed reveals a decline in published clinical trials on the topic. In the ten-year period from 2002 to 2012, there were 51 published randomized controlled clinical trials on herb-drug interactions, but in the subsequent decade, that number dropped to just 25.

The time for a globally coordinated effort to understand and regulate botanical medicines is long overdue. As these products become more integrated into the daily lives of millions, it is imperative that we bridge the gap between historical tradition and modern pharmacology. We must move beyond the idea that ‘natural is safe’ fallacy and dedicate the necessary resources to research, regulation, and education. This will require a collaborative approach that brings together researchers, regulatory agencies, and healthcare providers to develop standardized methodologies and a centralized database for reporting and tracking these interactions. Only by doing so can we ensure that the use of botanical medicine is not just a nod to tradition, but a truly safe and informed choice.

References

1. World Health Organization. (2002). WHO Traditional Medicine Strategy 2002-2005. Geneva, Switzerland.
2. Newman, D. J., & Cragg, G. M. (2020). Natural Products as Sources of New Drugs over the Last 40 Years. Journal of Natural Products, 83(3), 770-803.
3. Posadzki, P., Watson, L. K., & Ernst, E. (2012). Prevalence of herbal medicine use in the US: A systematic review. European Journal of Clinical Pharmacology, 68(11), 1395-1402.
4. Kaptchuk, T. J., & Eisenberg, D. M. (2001). The persuasive placebo: A re-examination of the relationship between mind, body, and drug. New England Journal of Medicine, 344(23), 1735-1744.
5. Zeller, A., & O’Brien, R. (2009). The potential for herb-drug interactions with cardiovascular medications. Journal of Cardiovascular Nursing, 24(4), 263-270.
6. Navarro, V. J., Barnhart, H., Bonkovsky, H. L., Davern, R. J., Fontana, H. R., Jones, D. B.,… & the DILIN Network. (2014). Liver Injury from Herbal and Dietary Supplements in the US. Hepatology, 60(2), 585-594.

Introduction

In children with Postural tachycardia syndrome (POTS), redistribution of blood upon standing due to gravity, increased sympathetic tone, decreased vagal activity resulting from muscle pump dysfunction, autonomic dysregulation, hyperadrenergic state, and autoimmunity contribute to reduced venous return and cardiac output.^1–5 These alterations can lead to recurrent syncope, seriously impacting the physical and mental health and quality of life of affected children. Therefore, identifying a simple, feasible, and cost-effective method for diagnosing and monitoring POTS is crucial.^4–6 Prior studies have indicated that the intensity of the first heart sound correlates positively with cardiac systolic function and may be used to assess physical activity tolerance in patients.⁷ Evaluation of the relationship between electrocardiogram(ECG) and heart sounds may assist in identifying patients with POTS.⁸

Electromechanical activation time (EMAT) is defined as the interval from the onset of the QRS complex on ECG to the first heart sound (S1, mitral valve closure), reflecting the time from electrical excitation to mechanical contraction of the myocardium.⁹ A shorter EMAT is associated with more efficient myocardial contraction. In this study, we employed a novel wearable patch to simultaneously record heart sounds and ECG signals.¹⁰ Analysis of these signals can help determine correlations with left ventricular ejection fraction.^11,12

Research Methods and Resources

Empowerment

This study was approved by the First Affiliated Hospital of the Medical College of Shihezi University Scientific and Technological Ethics Committee. All participants and their guardians provided written informed consent after being fully informed of the study’s purpose, content, and methods.

Study Subjects

From December 2022 to September 2024, fifty consecutive outpatients or inpatients were enrolled: 25 children with POTS (diagnosed by head-up tilt test [HUT/HUTT]) and 25 healthy controls.

Inclusion Criteria

① POTS was diagnosed according to the Chinese Medical Association’s Pediatric Syncope Guidelines (2016 Revision);¹³

② Age between 5 and 14 years;

③ Complete clinical data;

④ Written informed consent from guardians.

Exclusion Criteria

① History of surgery, metabolic disease (such as chronic renal failure, hypertension, obesity, diabetes), cardiovascular disease (congenital heart disease, arrhythmia), or neurological disorders;

② Use of hormone drugs or renin-angiotensin-aldosterone system inhibitors within 3 months;

③ Noncooperation during HUTT;

④ Refusal to sign informed consent;

⑤ Incomplete clinical data.

Data Collection

Heart Sound and ECG Signals Were Acquired Synchronously

The study used a wearable synchronous heart sound ECG data sensor acquisition system developed by Wenxin Technology Company (Beijing, China). The device consists of a reusable central component and a single-use patch (Figure 1). The disposable patch is stuck on the central piece and then attached to the chest wall of the patient. The 2 circular patches are the electrodes for the single-lead ECG. The sound sensor is in the center of the reusable part. The device can automatically detect ECG and heart sounds at the same time and digitize the signal and send it to a smartphone or tablet via Bluetooth. The data can also be sent to a cloud-based data center for archiving and analysis (Figures 2 and 3).

Figure 1 Operation flow of wearable heart-ECG monitoring device.

Figure 2 Example heart sound ECG. Mi-Ti: The time between mitral valve closure and tricuspid valve closure. Az-P2: Time between aortic valve closure and pulmonary valve closure. EMAT: Heart electromechanical activation time (electromechanical activation time) represents the time from the onset of ventricular excitation to mitral valve closure, that is, the time from ORs wave initiation to Ml. LVST: left ventricular systolic time, representing the time interval from Slto S2.

Figure 3 Flow chart.

Heart Sound and Electrocardiogram Related Indicator Tests

① Mi-Ti: The time between mitral valve closure and tricuspid valve closure. ② Az-P2: Time between aortic valve closure and pulmonary valve closure. ③ EMAT: Heart electromechanical activation time represents the time from the onset of ventricular excitation to mitral valve closure, that is, the time from ORs wave initiation to Ml. ④ LVST (left ventricular systolic time): Representing the time interval from Slto S2 (Figure 2). ⑤ LVET (Left Ventricular Ejection Time) is the duration of blood ejection from the left ventricle into the aorta during systole, reflecting ventricular contractile efficiency and aortic valve function.

Statistical Analysis

Based on the results of the normality test of the data, intergroup comparisons between the experimental and control groups were performed as follows: if the data conformed to a normal distribution (verified by the Shapiro–Wilk test), an independent samples t-test was used and expressed as the mean±standard deviation (); if the data were not normally distributed, a Mann–Whitney U-test was used, and the distribution was characterized by the median and interquartile range (IQR) to characterize the distribution. Two-way ANOVA was used to evaluate the effects of different groups (POTS vs control) and body positions (supine vs upright) on EMAT values. Precision-recall curve (PRC) was used for parameters associated with the diagnosis of postural tachycardia syndrome. SPSS 26.0 software (IBM, USA) was used for statistical analysis. P<0.05 was considered statistically significant.

Results

Comparison of Gender, Age and Body Mass Index (BMI) Between POTS Group and Control Group

Age Characteristics

The age distribution was similar in both groups, with a mean age of 9±5 years (median 11 years, interquartile distance 4) in the POTS group and 9±5 years (median 10 years, interquartile distance 3) in the control group. The Mann–Whitney U-test showed no statistical difference in age between the two groups (U=261.5, p=0.317) (Table 1).

Table 1 Comparison of Age, Gender and BMI Between POTS Group and Control Group

Gender Composition

The male-to-female ratio was 13:12 in the POTS group and 15:10 in the control group, and the gender distribution was generally balanced between the two groups (Table 1).

Bmi

The mean value of BMI was 13.8±1.2 kg/m² (median 14.0, IQR 12.5–15.0) in the POTS group and 13.7±1.1 kg/m² (median 13.8, IQR 12.5–14.9) in the control group. Statistical analysis based on non-parametric tests showed that the difference in BMI between the two groups was not statistically significant (U=301.0, P=0.682) (Table 1).

The POTS group and the control group were comparable in terms of baseline characteristics such as age, gender and BMI (P>0.05), which met the balanced requirements for case-control studies (Table 1).

The control group showed no significant orthostatic tachycardia, with mean supine and upright heart rates of 78.38 ± 9.56 bpm and 78.08 ± 13.63 bpm, respectively (P = 0.8434), whereas the POTS group exhibited a dramatic increase on standing from 81.04 ± 9.88 bpm to 111.04 ± 9.88 bpm (P < 0.0001) (Table 2).

Table 2 Comparison of Supine and Upright Heart Rates Between Control and POTS Groups

Details electromechanical intervals in POTS patients (n = 25): EMAT shortened significantly from 75.71 ± 9.16 ms supine to 70.90 ± 10.86 ms upright (P = 0.0051), and EMAT% rose from 9.18 ± 1.43% to 11.58 ± 1.50% (P < 0.001). Left ventricular ejection time (LVET) fell from 277.58 ± 23.18 ms to 231.44 ± 29.07 ms (P < 0.001), and corrected LVET decreased from 2366.25 ± 220.35 to 2293.78 ± 266.40 (P = 0.043) (Table 3).

Table 3 POTS Group (n=25)

Control subjects also experienced a non-significant reduction in EMAT (58.92 ± 4.10 ms to 55.50 ± 9.89 ms; P = 0.100) and a modest rise in EMAT% (10.04 ± 1.41% to 10.83 ± 0.72%; P = 0.022) on standing. LVET shortened markedly from 257.67 ± 23.43 ms to 217.58 ± 17.30 ms (P < 0.001), and corrected LVET declined from 2591.33 ± 193.61 to 2371.92 ± 186.95 (P < 0.001) (Table 4).

Table 4 Control Group (n=25)

Compared to POTS versus controls: raw EMAT was significantly longer in POTS than controls in both supine and upright positions (P < 0.001), while EMAT% differences (P = 0.154 supine, 0.147 upright) and upright LVET (P = 0.188) were not significant. Supine LVET (P = 0.048) and supine corrected LVET (P = 0.014) did differ between groups (Table 5).

Table 5 POTS Group-Control Group P value

Quantifies orthostatic EMAT change (upright–supine): POTS patients had a mean increase of 3.39 ± 5.91 ms versus 0.58 ± 5.70 ms in controls (P = 0.038), underscoring EMAT’s potential value as an orthostatic diagnostic marker (Table 6).

Table 6 Comparison of Differences Between Upright and Supine Positions Between Control and POTS Groups

In both positions, the POTS group exhibits higher median and mean values than the control group, with wider interquartile ranges and longer whiskers indicating greater variability. In the supine position, the POTS median (78.5 ms) exceeds the control median (57 ms), and likewise in the upright position (POTS 70 ms vs control 56 ms). Red dots mark group means. This visualization highlights both the main effects of group and position and suggests a pronounced group–position interaction (Figure 4).

Figure 4 Boxplot of Control vs POTS in Supine and Upright.

Precision–Recall Curves (PRC) for Supine and Upright EMAT in POTS Diagnosis

The supine curve (solid line) achieves an average precision (AP) of 0.84, maintaining high precision even at elevated recall levels. The upright curve (dashed line) yields an AP of 0.88, indicating slightly better overall diagnostic performance. Overlaying both curves highlights that EMAT performs well in both body positions, with the upright measurement offering a marginally higher balance of sensitivity and positive predictive value (Figure 5).

Figure 5 Precision-Recall Curves for EMAT in POTS Diagnosis.

Discussion

The most common clinical methods for assessing postural tachycardia syndrome are the head-up test, the head-up tilt test, and the nitroglycerin-challenged head-up tilt test. These tests are not easily accessible for routine or large-scale screening, as they require a healthcare professional and must be performed in a controlled clinical environment.¹³ Alternatively, heart sounds can be assessed using a stethoscope at various auscultation sites or recorded by specialized transducers and converted into time-series signals, known as phonocardiograms.¹⁴ Phonocardiograms are able to detect heart sound components that are inaudible or difficult to perceive by the human ear. They help distinguish easily confused sounds, determine the timing and characteristics of heart sounds and murmurs, and provide valuable information regarding cardiac hemodynamics, structural integrity, and function. Phonocardiography converts collected sound data into electronic signals, which are then digitized and transmitted to network terminals for automatic analysis, graphical visualization, and storage. This further enhances the clinical utility of heart sound analysis and promotes the development of telemedicine.^15,16 Acoustic cardiography (ACG) is a new computer-aided diagnosis technology based on the simultaneous acquisition and analysis of ECG and heart sound signals. By placing dual sensing elements in one or both parts of the standard chest leads V2, V3 or V4, the ECG and heart sound signals are simultaneously collected.¹⁷ Computer-aided analysis and automatic report generation offer advantages such as non-invasiveness, ease of operation, cost-effectiveness, and intelligence, while enabling real-time and dynamic ECG monitoring.¹⁸

The researchers found that EMAT and LVST were related to left ventricular pressure changes and myocardial contractility.¹⁹ A shortened LVST or a prolonged EMAT indicates reduced left ventricular systolic function, demonstrating that changes in heart sound features can effectively reflect left ventricular dysfunction and diminished cardiac reserve caused by abnormal cardiac hemodynamic parameters. On the strength of the S1 phonocardiogram were positively correlated with the contraction of the heart function, EMAT is closely related to the cardiac systolic function, which can be used to assess the tolerance of patients to physical activity.²⁰ In this study, a patch device was used to analyze heart sounds and ECG signals. The wearable device can be used not only by health care providers but also by patients themselves outside the hospital to assess cardiac function. The results are helpful for the clinical diagnosis and out-of-hospital monitoring of postural tachycardia syndrome in children.

Yamanouchi et al performed echocardiography on POTS patients and normal controls during baseline supine and upright tilt tests and found that, compared with normal controls, the syncope group had a faster rate of decline in left ventricular end-diastolic volume during tilt and a significant decrease in stroke volume and ejection fraction.²¹ In patients with POTS, early left ventricular end-systolic pressure and wall stress-corrected shortening of the left internal diameter after HUTT were significantly reduced, indicating a marked decline in cardiac afterload and myocardial contractility.

In this study, EMAT is defined as from ECG Q wave to phonocardiogram S1 first peak period. It reflects the progression from electrical activity to mechanical movement. It can be measured by the time interval between the Q wave of the ECG and the S1 of the heart sound. It was found that there was no statistically significant difference in S1–S2 interval between the POTS and control groups. Based on animal experiments, Kamran et al concluded that EMAT is not related to heart rate and that EMAT values can be directly compared across groups.

The results of this study showed that in the POTS group, heart rate increased significantly from the supine to the upright position (81.04±9.88 bpm vs 111.04±9.88 bpm, P<0.0001), whereas there was no significant difference in heart rate between positions in the control group (78.38±9.56 bpm vs 78.08±13.63 bpm, P=0.8434), confirming the abnormal heart rate response to postural change in children with POTS.

For electromechanical parameters, EMAT in the POTS group was significantly higher than in the control group in both supine and upright positions (75.71±9.16 ms vs 58.92±4.10 ms; 70.90±10.86 ms vs 55.50±9.89 ms, both P<0.001), and the change in EMAT (upright-supine) in the POTS group (3.39±5.91 ms) was greater than that in the control group (0.58±5.70 ms, P=0.038). EMAT% in the POTS group increased significantly in the upright position (9.18±1.43% vs 11.58±1.50%, P<0.001), while only a mild increase was observed in the control group. Left ventricular ejection time (LVET) decreased with postural change in both groups, but supine and corrected LVET were significantly lower in the POTS group compared to controls (P=0.048, P=0.014). Precision-recall curve (PRC) analysis showed that the average precision (AP) of EMAT in distinguishing POTS from controls was 0.84 in the supine position and 0.88 in the upright position, indicating good predictive performance.

These data suggest that EMAT and its postural change can serve as sensitive electromechanical indicators of autonomic dysfunction in pediatric POTS. In response to upright stress, POTS patients experience enhanced sympathetic activity, resulting in a marked increase in heart rate and a shortening of EMAT, reflecting abnormal coordination between ventricular filling and contraction. The concurrent changes in EMAT% and LVET further indicate altered timing between mechanical and electrical cardiac events in POTS, closely associated with impaired postural regulation.

Study Limitations

One limitation of our work is that we did not obtain concurrent echocardiographic timing of mitral-valve closure to validate the EMAT interval measured on our synchronized phonocardiogram/ECG recordings. At the time of data collection, real-time echocardiography was not performed in parallel with phonocardiography—equipment and sonographer availability did not allow simultaneous recording of valve motion. Although this technique is good at identifying reduced LV ejection fraction, there are some limitations. Sound is a complex signal. The quality of the collected ACG signal is greatly affected by endogenous and exogenous factors. The endogenous factors include the factors affecting sound transmission such as the degree of obesity of the subject, the presence or lack of lung lesions, pleural and pericardial effusion, and respiratory rhythm, etc. The exogenous factors are mainly the quiet degree of the operating environment. Exogenous factors can be controlled artificially, but the influence of endogenous factors on ACG parameters is still insufficiently studied. Moreover, the heart sound signals collected by different sensors and at different chest standard lead positions are different.

Conclusions

EMAT and its postural variation, measured using a wearable synchronized phonocardiogram-ECG device, are sensitive, noninvasive markers for distinguishing pediatric POTS from healthy controls. Integration of wearable monitoring into clinical practice could facilitate diagnosis and follow-up in pediatric POTS. Larger, prospective studies are warranted to validate and optimize these findings.

Abbreviations

POTS, Postural Tachycardia Syndrome; ECG, Electrocardiogram; EMAT Electromechanical activity time; BMI, Body mass index; IQR, Interquartile range; ACG, Acoustic cardiography; LVST, Left ventricular systolic time; LVET, Left Ventricular Ejection Time; PRC, Precision-recall curve; HUTT, Head-Up Tilt Test; HUT, Head-Up Test.

Data Sharing Statement

The data supporting the findings of this investigation are available upon reasonable request from the corresponding author.

Ethical Approval and Consent to Participate

This study was conducted in accordance with the principles of the Declaration of Helsinki. Written informed consent was obtained from the parents or legal guardians of all participating children.

Ethical Approval

This study was approved by the Ethics Committee of the First Affiliated Hospital of the Medical College of Shihezi University Scientific and Technological Ethics Committee, approved of the number: KJ2023-178-02.

Consent to Participate

Written informed consent was obtained from the legal guardians of all child participants prior to enrollment in the study.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Funding

XPCC Science and Technology Research Plan in Key Areas (2023AB018-11), XPCC 2023 Talent Development Fund (CZ001209), XPCC Science and Technology Support Special Plan (2022ZD024), Innovation and Development Special Plan of Shihezi University (CXFZ202115), Talent Development Fund – Key Laboratory of the Corps – Clinical Medical Research Center for Children’s Diseases of the First Affiliated Hospital of the Corps (CZ001209/ Bing Caixing [2023] 80-2023).

Disclosure

All authors report no relationships that could be construed as a conflict of interest. All authors take responsibility for all aspects of reliability and freedom from bias of the data presented and their discussed interpretation.

References

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Introduction

The annular pancreas is a rare congenital malformation that causes duodenal obstruction at birth.¹ The annular pancreas is characterized by partial or total encirclement of the second segment of the duodenum by a strip of pancreatic tissue during embryonic development.² It is commonly found below the ampulla of Vater in about 85% of confirmed cases and rarely above 15%.³ Annular pancreas occurs in approximately 1 out of every 20,000 live births.⁴ Due to the infrequency of this congenital condition, the specific cause related to the formation of an annular pancreas is not well established. Still, the annular pancreas is regarded as an embryopathy.⁵ In the initial four to eight weeks of embryonic development, the pancreas typically forms as the dorsal and ventral pancreatic buds rotate and fuse, driven by the expansion of the duodenum. The ventral bud gives rise to the inferior section of the head and the uncinate process of the pancreas, while the dorsal bud develops into the body and tail of the pancreas. The formation of the annular pancreas is thought to be a migration defect occurring due to the inability of the ventral bud to rotate and grow in a way that fully or partially surrounds the second portion of the duodenum.^6,7

Symptoms associated with annular pancreas can vary greatly from one individual to another. In certain instances, it may lead to intense symptoms shortly after delivery, whereas in other cases, it could stay asymptomatic throughout a person’s life.⁴ In neonates, typical symptoms include difficulties with feeding, vomiting, and abdominal bloating. In adults, the symptoms often resemble those of gastric outlet obstruction, including persistent abdominal pain, nausea, a feeling of fullness after eating, and vomiting.⁸ The intensity of the symptoms is linked to the degree of pressure exerted by the annular pancreas on the duodenum.⁴ Nevertheless, the severity of duodenal obstruction and the accompanying obstructive symptoms can vary, and there have been cases of the unrecognized annular pancreas being found in teenagers or even adults.¹ Understanding the clinical features of patients with an annular pancreas is tremendously valuable in diagnosing this condition. Typically, annular pancreas is identified during routine prenatal ultrasounds through the detection of the double bubble sign in the fetal abdomen, allowing for both diagnosis and treatment to be effectively carried out shortly after delivery.⁹ Different imaging methods, such as ultrasonography, X-ray, endoscopic retrograde cholangiopancreatography (ERCP), and computed tomography (CT), can also be used to diagnose an annular pancreas. In adults who are affected, CT is more frequently used.¹⁰ A definitive diagnosis of the annular pancreas relies on imaging studies and findings observed during surgery. Surgery is the gold standard for diagnosing the annular pancreas. Imaging studies play a suggestive role in the diagnosis before surgery.¹¹ CT and MRI reveal pancreatic tissue surrounding the duodenum.¹² There are no established guidelines or protocols for managing an annular pancreas.¹³ Several surgical techniques can be employed to treat the annular pancreas, with the primary goal being to alleviate the obstructive symptoms associated with this congenital condition.¹⁰ Duodenoduodenostomy, duodenojejunostomy, or gastroduodenostomy may be carried out, and the section of the duodenum, along with a ring of pancreatic tissue, can be excised as a single unit.¹² Here, we report a rare case of annular pancreas in a 13-year-old boy with a delayed clinical presentation of a partial duodenal obstruction (obstruction of the first part of the duodenum). This case highlights the challenges of diagnosis, which was achieved through surgical exploration in a resource-limited setting, and it was treated successfully with gastroduodenostomy.

Case Presentation

A 13-year-old boy came to the emergency department complaining of recurrent episodes of vomiting and abdominal pain over the past 3 years. The vomiting was non-bilious, projectile, and occurred after meals. Its frequency and severity have been gradually increasing. The abdominal pain was primarily in the epigastric region and was relieved after vomiting. On physical examination, the patient was in fair general condition, alert, and slightly dehydrated with normal vital parameters. The patient’s systemic examination was normal. On laboratory examination, the white blood cell count, hemoglobin, electrolytes, urea, creatinine, and albumin were all within normal limits. On imaging, plain CT and post-IV contrast CT of the abdomen and pelvis revealed marked distention of the stomach with abrupt tapering of the first part of the duodenum and collapse of the rest of the duodenum. The pancreas was normal in size and showed homogeneous enhancement on post-contrast scans, with no evidence of calcifications. The rest of the small bowel loops, liver, gall bladder, spleen, kidneys, urinary bladder, and abdominal aorta were normal (Figure 1). The patient underwent a surgical exploration. Intraoperatively, a band of pancreatic tissue is found encircling the first part of the duodenum, causing an obstruction (Figure 2), with marked dilatation of the stomach (Figure 3), without any additional abnormal findings. A gastroduodenostomy was performed. The patient experienced an uneventful postoperative recovery, during which he received intravenous fluids, analgesics, and antibiotics. On the third day after surgery, oral sips were introduced, gradually increasing the diet from liquids to semi-liquids and then to full solid foods over three weeks. After discharge from the hospital, the patients attended follow-up appointments and showed improvement with no further vomiting, abdominal pain, or negative complications.

Figure 1 Abdominal CT shows marked distension of the stomach (thick arrows) with abrupt tapering of the first part of the duodenum and collapse of the rest of the duodenum.

Figure 2 Intraoperative image showing the pyloric region of the stomach (black arrow), a band of pancreatic tissue encircling the first part of the duodenum, causing obstruction (green asterisks). The second part of the duodenum is normal (yellow arrow).

Figure 3 Intraoperative image showing a dilatation of the stomach (blue asterisks).

Discussion

The annular pancreas is a rare congenital anomaly characterized by the abnormal rotation of the pancreas. This condition infrequently occurs in adults.¹¹ The differential diagnosis can be divided into intrinsic and extrinsic. Notable intrinsic causes to consider include duodenal atresia, duodenal stenosis, paraduodenal hernias, Meckel diverticulum, and duodenal webs. At the same time, significant extrinsic factors to consider are gut malrotation and midgut volvulus. In adults suspected of having annular pancreas, peptic ulcer disease, pancreatic divisum, and primary duodenal and pancreatic cancers should also be included in the differential diagnosis.^14,15 Various imaging modalities are being actively considered for diagnosing annular pancreas. CT is used to diagnose and analyze the annular pancreas.¹⁰ CT results indicate an enlargement of the pancreatic head with enhanced visibility of the second portion of the duodenum.¹³ In a case of annular pancreas reported by Moon, an abdominal CT scan revealed pancreatic tissue surrounding the second part of the duodenum, leading to the diagnosis of an annular pancreas.¹ In this patient, plain CT and post-IV contrast CT of the abdomen and pelvis revealed marked distention of the stomach with abrupt tapering of the first part of the duodenum and collapse of the rest of the duodenum. The pancreas was normal in size and showed homogeneous enhancement on post-contrast scans, with no evidence of calcifications (Figure 1). In this case, the preoperative imaging with plain CT provided features of gastric outlet obstruction, which made the diagnosis challenging. This challenge necessitated reliance on surgical exploration for accurate diagnosis. Although the patient’s clinical characteristics are not unique to the annular pancreas, they provided some clues to the diagnosis, which necessitated the decision to perform surgical exploration. The definitive diagnosis was confirmed by surgical exploration, which revealed a band of pancreatic tissue encircling the first part of the duodenum, causing an obstruction. In contrast, the second part of the duodenum was normal (Figure 2). This finding is consistent with a case reported by Jha et al.⁸ This decision aligns with the existing literature, which emphasizes the importance of having a thorough understanding of the clinical characteristics of the annular pancreas and its associated anomalies when managing this uncommon congenital anomaly.¹⁰ A significant number of individuals with this anomaly stay asymptomatic for their entire lives and are frequently identified incidentally through imaging studies or during autopsies. Nevertheless, a small percentage of patients with an annular pancreas may show clinical symptoms either in childhood or later in life, typically between the ages of 20 and 50.¹⁶ The clinical presentation of the annular pancreas varies by age, resulting in differences in diagnosis.¹³ The emergence of advanced diagnostic techniques has led to an increased recognition of this condition. However, despite radiological advancements, surgical confirmation is required in approximately 40% of annular pancreas cases, establishing it as the gold standard.^13,16 The clinical presentation of the annular pancreas varies by age, resulting in age-related variations in management. The approach to treating an annular pancreas varies based on its clinical presentation. Surgical procedures using different bypass methods, such as duodenoduodenostomy, gastrojejunostomy, gastroduodenostomy, and duodenojejunostomy, are necessary.¹³ However, the decision should be customized for the individual patient.¹⁶ In our patient, we successfully performed a gastroduodenostomy with a transverse incision of the pylorus and a longitudinal incision of the duodenum, resulting in a diamond-shaped anastomosis. After more than six months of follow-up, the patient was feeling well and started to gain weight. The annular pancreas is a rare condition that warrants attention in the differential diagnosis of recurrent vomiting and abdominal pain. This unusual formation of pancreatic tissue encircling the duodenum can lead to gastrointestinal obstruction, which may manifest as persistent nausea, abdominal pain, and vomiting. We recommend that clinicians, especially surgical pediatricians, be vigilant in considering this possibility when evaluating patients with these symptoms.

Conclusion

This case underscores that the annular pancreas, although a congenital condition typically detected in the neonatal period, can manifest later in childhood with insidious and non-specific symptoms such as recurrent non-bilious vomiting and epigastric pain. In our 13-year-old patient, preoperative imaging provided features of gastric outlet obstruction, necessitating surgical exploration for confirmation. The subsequent intraoperative identification of a pancreatic tissue band encircling the duodenum, along with the successful execution of a gastroduodenostomy, highlights not only the diagnostic challenges but also the efficacy of tailored surgical management in resource-limited settings. The favorable postoperative recovery, marked by the resolution of symptoms and gradual weight gain, reinforces the importance of maintaining a high index of suspicion for the annular pancreas in adolescents presenting with chronic gastrointestinal symptoms. This report serves as a reminder that even in the absence of classical radiological findings, meticulous clinical evaluation coupled with timely surgical intervention can markedly improve patient outcomes. Furthermore, documenting such cases is crucial for deepening our understanding of the variable presentations of the annular pancreas. It may pave the way for the development of more standardized diagnostic and therapeutic protocols in the future.

Ethics Statement

An institution’s ethics committee approval is not required for the case reports.

Informed Consent Statement

Written informed consent was obtained from the patient’s parent for the publication of this case report and any accompanying images. The patient’s parent was told about the purpose of this publication and that his identity would be protected.

Acknowledgments

We would like to thank all the participants, Kalkaal Hospital, and the Simad University Research Center for their valuable contributions to the case report.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising, or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors declare no conflicts of interest in this work.

References

1. Moon SB. Annular pancreas in an 11-year-old girl: a case report. Int Med Case Rep J. 2017;10:65–67. doi:10.2147/IMCRJ.S128867

2. Nagpal SJS, Peeraphatdit T, Sannapaneni SK, et al. Clinical spectrum of adult patients with annular pancreas: findings from a large single institution cohort. Pancreatology. 2019;19(2):290–295. doi:10.1016/j.pan.2018.12.009

3. Benassai G, Perrotta S, Furino E, et al. “Ductal adenocarcinoma in anular pancreas”. Int J Surg. 2015;21(Suppl 1):S95–7. doi:10.1016/j.ijsu.2015.04.086

4. Taşdemir Ü, Demirci O. Clinical Analysis of Congenital Duodenal Obstruction and the Role of Annular Pancreas. Medicina. 2025;61(1):61. doi:10.3390/medicina61010061

5. Nobukawa B, Otaka M, Suda K, Fujii H, Matsumoto Y, Miyano T. An annular pancreas derived from paired ventral pancreata, supporting Baldwin’s hypothesis. Pancreas. 2000;20(4):408–410. doi:10.1097/00006676-200005000-00012

6. Sandrasegaran K, Patel A, Fogel EL, Zyromski NJ, Pitt HA. Annular pancreas in adults. AJR Am J Roentgenol. 2009;193(2):455–460. doi:10.2214/AJR.08.1596

7. Alahmadi R, Almuhammadi S. Annular pancreas: a cause of gastric outlet obstruction in a 20-year-old patient. Am J Case Rep. 2014;15:437–440. doi:10.12659/AJCR.891041

8. Jha S, Luitel S, Kushwaha N, Singh S, Jha SK. Partial Annular Pancreas Causing Obstruction of the First Part of the Duodenum: an Exceedingly Rare Conundrum-A Rare Case Report and Comprehensive Literature Review. Clin Case Rep. 2025;13(7):e70614. doi:10.1002/ccr3.70614

9. Zhang B, Zhang W, Hu Y, Pang H, Yang H, Luo H. Evaluation of prenatal and postnatal ultrasonography for the diagnosis of fetal double bubble sign. Quant Imaging Med Surg. 2024;14(9):6386–6396. doi:10.21037/qims-24-445

10. Plutecki D, Ostrowski P, Bonczar M, et al. Exploring the clinical characteristics and prevalence of the annular pancreas: a meta-analysis. HPB (Oxford). 2024;26(4):486–502. doi:10.1016/j.hpb.2024.01.006

11. Yi D, Ding XB, Dong SS, Shao C, Zhao LJ. Clinical characteristics of adult-type annular pancreas: a case report. World J Clin Cases. 2020;8(22):5722–5728. doi:10.12998/wjcc.v8.i22.5722

12. Azadi J, Zaheer A. Case 67: annular Pancreas. In: Pancreatic Imaging: A Pattern-Based Approach to Radiologic Diagnosis with Pathologic Correlation. Cham: Springer International Publishing; 2017:287.

13. Ahmetgjekaj I, Roy P, Hyseni F, et al. Annular pancreas: beneath the intestinal obstruction-A case report. Radiol Case Rep. 2023;18(3):1364–1367. doi:10.1016/j.radcr.2022.11.083

14. Whittingham-Jones PM, Riaz AA, Clayton G, Thompson HH. Annular pancreas – a rare cause of gastric obstruction in an 82-year-old patient. Ann R Coll Surg Engl. 2005;87(1):W13–5. doi:10.1308/147870804902

15. Kweun JA, Kang HM, Kim JE, Park SJ. Annular Pancreas: a Rare Cause of Upper Gastrointestinal Bleeding in Adults. Korean J Gastroenterol. 2022;79(4):182–186. doi:10.4166/kjg.2022.012

16. Cai H, Wang X, Cai YQ, Li YB, Meng LW, Peng B. Laparoscopic Roux-en-Y duodenojejunostomy for annular pancreas in adults: case report and literature review. Ann Transl Med. 2018;6(11):211. doi:10.21037/atm.2018.05.13

Researchers have created a remarkable new approach to repairing spinal cord injuries by merging 3D printing, stem cells, and lab-grown tissues.

They engineered tiny scaffolds that guide stem cells to form nerve fibers capable of bridging severed spinal cords. In experiments with rats, this method restored nerve connections and movement, offering new hope that one day similar techniques could help people living with paralysis.

Breakthrough in Spinal Cord Injury Treatment

For the first time, scientists at the University of Minnesota Twin Cities have successfully combined 3D printing, stem cell science, and lab-grown tissues to explore a new approach for treating spinal cord injuries.

Details of the work appear in the journal Advanced Healthcare Materials, a peer-reviewed scientific journal.

Spinal cord injuries affect more than 300,000 people in the United States, according to the National Spinal Cord Injury Statistical Center. There is still no treatment that can fully reverse the paralysis and long-term damage these injuries cause. One of the biggest barriers to recovery is that nerve cells die, and the remaining fibers cannot regrow across the site of injury. The Minnesota team designed their study to directly address this challenge.

3D-Printed Scaffolds and Stem Cells

The researchers developed a specialized 3D-printed structure known as an organoid scaffold. This tiny framework contains microscopic channels that are filled with spinal neural progenitor cells (sNPCs). These cells, which originate from human adult stem cells, can divide and develop into specific types of mature nerve cells.

“We use the 3D printed channels of the scaffold to direct the growth of the stem cells, which ensures the new nerve fibers grow in the desired way,” said Guebum Han, a former University of Minnesota mechanical engineering postdoctoral researcher and first author on the paper who currently works at Intel Corporation. “This method creates a relay system that when placed in the spinal cord bypasses the damaged area.”

Successful Transplants in Animal Models

In their study, the researchers transplanted these scaffolds into rats with spinal cords that were completely severed. The cells successfully differentiated into neurons and extended their nerve fibers in both directions—rostral (toward the head) and caudal (toward the tail)—to form new connections with the host’s existing nerve circuits.

The new nerve cells integrated seamlessly into the host spinal cord tissue over time, leading to significant functional recovery in the rats.

The method involves creating a unique 3D-printed framework for lab-grown organs, called an organoid scaffold, with microscopic channels. Credit: McAlpine Research Group, University of Minnesota

Toward Future Clinical Translation

“Regenerative medicine has brought about a new era in spinal cord injury research,” said Ann Parr, professor of neurosurgery at the University of Minnesota. “Our laboratory is excited to explore the future potential of our ‘mini spinal cords’ for clinical translation.”

While the research is in its beginning stages, it offers a new avenue of hope for those with spinal cord injuries. The team hopes to scale up production and continue developing this combination of technologies for future clinical applications.

Reference: “3D-Printed Scaffolds Promote Enhanced Spinal Organoid Formation for Use in Spinal Cord Injury” by Guebum Han, Nicolas S. Lavoie, Nandadevi Patil, Olivia G. Korenfeld, Hyunjun Kim, Manuel Esguerra, Daeha Joung, Michael C. McAlpine and Ann M. Parr, 23 July 2025, Advanced Healthcare Materials.
DOI: 10.1002/adhm.202404817

In addition to Han and Parr, the team included Hyunjun Kim and Michael McAlpine from the University of Minnesota Department of Mechanical Engineering; Nicolas S. Lavoie, Nandadevi Patil and Olivia G. Korenfeld from the University of Minnesota Department of Neurosurgery; Manuel Esguerra from the University of Minnesota Department of Neuroscience; and Daeha Joung from the Department of Physics at Virginia Commonwealth University.

This work was funded by the National Institutes of Health, the State of Minnesota Spinal Cord Injury and Traumatic Brain Injury Research Grant Program and the Spinal Cord Society.

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Nutrition is an important and often overlooked aspect of the oncology treatment paradigm that could significantly impact the health and quality of life of patients undergoing radiation therapy, chemotherapy, and other modalities for cancer.

Denise B. Reynolds, RD, spoke with CancerNetwork® about common nutritional challenges she observes in patients undergoing treatment for cancer or in cancer survivors, as well as strategies she employs to help mitigate their frequency and severity. Specifically, she addressed common treatment-emergent adverse effects (TEAEs) associated with cancer treatment, such as nausea and vomiting, weight gain/loss, taste and smell alterations, and mucositis or dysphagia.

She began by highlighting appetite-related concerns that emerge with the cancer itself, with a particular focus on weight loss. Reynolds expressed that unintentional weight loss often prompts patients to consult with a dietitian. Furthermore, she touched upon the use of nutritional supplements in patients with cancer, suggesting that some iron supplementation may be used for anemia, but she discouraged the use of immune-boosting supplementation, which can interfere with cancer treatment.

Reynolds then outlined strategies for combating various TEAEs, such as foods having a metallic taste and electrolyte-enriched beverages for nausea, and counteracting taste changes with contrasting food types, such as adding spices to patients who report food tasting bland. For longer-term health in patients who have finished treatment or who are cancer survivors, Reynold’s practice recommends patients adhere to the New American plate diet, which restricts the intake of animal proteins and encourages a greater consumption of fruits, vegetables, whole grains, nuts, and fiber, which she expressed may help patients reach and maintain a healthy weight.

In conclusion, she touched upon optimal strategies for collaboration among dietitians and oncologists.

CancerNetwork: What are some of the most common nutritional challenges you see in patients with cancer, and how do you approach these?

Reynolds: Many times, the cancer itself will cause issues with appetite, [gastrointestinal] upset, things like that: it is different for everyone. Cancer treatment can make those situations worse, but some of the issues that they have start with weight loss, which is one of the reasons why they go to their doctor. They [may say] “I have lost this weight. I do not know why I am not eating.” They may know that they have a loss of appetite, but they do not feel like they have done anything to create that weight loss themselves. It was not intentional, and that is one of the things that drives them to the doctor to figure out what is going on with them.

Are there any specific vitamins or minerals that you find are consistently deficient in patients with cancer, and do you recommend supplementation?

Reynolds: It is different for every cancer, and cancer treatment is individualized. There are issues. For example, if you have nausea and vomiting, then you are [likely] losing a lot of fluid [and] you are not keeping the calories down. Overall, if someone is eating well, they should not be deficient in any specific vitamins. Now, the cancer treatment itself can cause anemia, because you are breaking down cells––breaking down red blood cells. A physician may ask that you take iron or may have an iron infusion. If you are deficient in vitamin D, which so many of us are, even without cancer, they might recommend a vitamin D supplement. Other than that, we do not recommend any supplements while you are receiving cancer care.

Certain supplements can be high in, say, antioxidants, and that can interfere with the chemotherapy [or] radiation. For [patients] who do not recognize that, they [may] have friends and family who give them high-powered supplements or drink something that helps boost their immune system, so to speak. We do not want that. That can interfere with some of the treatment that we offer our patients.

What nutritional strategies do you recommend to ensure adequate intake [and combat vomiting and nausea]?

Reynolds: As a dietitian, you will probably often hear me say small, frequent meals… quite a bit, [Many] times, you cannot eat a [food in volume or] sit down and eat a regular-sized meal. Eating a little bit throughout the day will help keep your nutrition level up, and it may actually help with the nausea. Unlike certain nausea that you get when you have the flu or food poisoning, you do not feel like eating, and you do not want to put anything in your stomach, but having something in your stomach during the nausea and vomiting from chemotherapy can help quell some of that nausea.

I think of it a lot like pregnancy nausea. I tell [patients] to keep crackers by their bed, to eat first thing in the morning to help quell that nausea. It is similar. Crackers, dry toast, and chicken noodle soup are things that are bland and comforting, things without [many] smells, because that smell can also trigger nausea for [patients], and trying to keep things as simple as possible. Replacing fluids–ginger ale can be helpful. Sometimes plain water can be a bit nauseating. Having something with electrolytes in it, like a Gatorade or a Pedialyte [may help].

What advice would you give patients to help cope and combat taste and smell changes?

Reynolds: One of the most common taste changes that we see is with one chemotherapy that makes [many] things taste like metal, and in those cases, we recommend using plastic forks or using chopsticks [and] eating foods that are frozen vs canned. Getting frozen vegetables and frozen fruits, vs canned [and] drinking out of a plastic bottle or with a straw so that you are not touching that metal, may help].

Some of the other taste changes we hear about are things tasting [abnormally] bitter. In that case, adding a bit of sweetness to your food can help, even if it’s a citrusy type of flavor.Chicken with orange sauce, or beef with orange sauce, something like that, will help bring a little bit of sweetness to the food and make it not taste quite so bitter. If something tastes bland, which we get [frequently] with our radiation patients, instead of adding extra salt, which we know is not good for you, adding strong spices like oregano, or if they can tolerate something spicy, go for a bit of hot sauce or chili powder, or something like that [can help].

If they are having any issues with their mouth––sore mouth or anything––then, of course, we want to avoid the spicy foods. All that being said, [we try] balancing whatever taste that you have with the opposite. If things are too sweet, balance it with something bitter. If something is too bitter, balance it with something sweet.

How do you manage the nutritional needs of patients with mucositis or dysphagia?

Reynolds: The mucositis and the mouth sores that can come from chemotherapy can also come from radiation to the head and neck. That beam can hit and cause inflammation on the inside of the mouth. Then dysphagia is trouble swallowing. The first thing is to try something soft, trying, say, scrambled eggs or a chicken salad, vs a chicken breast. Something that is soft and moist will be a bit easier to [swallow].

Things that are cold soothe the mouth. [Many] times, we have patients who will hold ice in their mouth to help freeze that area a little bit, make it feel a bit more soothing. Rinsing the mouth out––keeping good oral care during that time [will help] if you are having sores in your mouth, which can lead to bacteria, and it can lead to things like gingivitis and infections of the mouth. Keeping the mouth rinsed clean with something, [an alcohol-free rinse], because [alcohol] would burn.

Spicy foods can be painful if you are having issues with dysphagia. Again, the softer foods, adding moisture, and cooking foods. If you are eating meat, cooking it in a crock pot can help bring some of the moisture back to the food and help it go down a bit easier. Adding gravies and sauces to foods can help with that as well.

For patients who have survived cancer, what nutritional advice would you give to help them promote even longer-term health?

Reynolds: We always follow the American Institute for Cancer Research guidelines. They have something called the New American plate, and it is similar to a Mediterranean-style diet, in that we are reducing the amount of red meat that they are eating, and then fish and chicken are in smaller portion sizes. We are trying not to overload [them] with animal proteins and bring back those fruits and vegetables, nuts, seeds, whole grains, increasing the amount of fiber that someone is getting, trying to get someone to reach a healthy weight, whether they are underweight or overweight. [We are] trying to get their nutrition status back to where they are reaching that healthy weight again.

Not necessarily nutrition-based, but we always want to get people moving again if they can. Fatigue is a common lingering effect for cancer survivors after they have finished their treatment, but eating a good, healthy diet, rich in fruits and vegetables and whole grains, and getting in some exercise can help with that fatigue. Lastly, staying hydrated, because it’s easy to get dehydrated, even again, for a healthy person. Making sure that, as a survivor, you are staying hydrated can also affect fatigue.

What is the best way for clinicians to collaborate with a registered dietitian to improve patient outcomes?

Reynolds: We have 18 dietitians here at Atrium Health, and most of our dietitians are helping patients while they are [undergoing] active treatment, and they are helping with those nutrition impact symptoms: the nausea, [gastrointestinal] upset, taste changes, weight loss, and all of the things that come surrounding a cancer treatment. Helping someone be the best they can to get through that treatment, just ask the nurse, ask your doctor for a referral to a dietitian, and we are more than happy to come talk to you, either on the phone or while you are in the clinic.

Is there anything else that you would like to highlight today?

Reynolds: [Remember] that food is fuel. We are always here to answer questions for you, whether it is about supplements or a particular food or a something you have heard [or to correct] misinformation. We can help clear that up for you. Always ask questions, always be your best advocate, and we are all here to help you through this journey.

Reference

Setting Your Table to Prevent Cancer. American Institute for Cancer Research. Accessed September 2, 2025. https://tinyurl.com/w7pfsc9d

Is it possible to treat obesity without reducing food intake? A new study co-led by Dr. Antonio Zorzano and Dr. Manuela Sánchez-Feutrie at the Institute for Research in Biomedicine (IRB Barcelona) suggests that this might be a possibility, at least in animal models. Published in Nature Communications, the research identifies a key role for Neuritin 1, a protein previously linked to the nervous system, which is also produced in brown adipose tissue, where it acts as a powerful driver of energy expenditure and metabolic health.

Unlike current anti-obesity and antidiabetic drugs, such as Ozempic or tirzepatide, which work by suppressing appetite, Neuritin 1 boosts energy burning without affecting food intake.

By increasing the levels of Neuritin 1 specifically in brown fat, we observed that the animals burned more energy, which helped prevent fat accumulation.”

Dr. Antonio Zorzano, professor at the University of Barcelona and researcher at CIBERDEM

This metabolic boost led to significant improvements in several health indicators, including reduced weight gain, improved insulin sensitivity, and lower liver inflammation, even in animals fed high-calorie diets.

Neuritin 1: a new player in energy metabolism

Previously described for its role in neuronal plasticity, Neuritin 1 is now shown to have a metabolic function in brown fat, a type of fat specialised in generating heat through a process known as thermogenesis. This process involves burning energy to maintain body temperature, particularly in response to cold. In this context, Neuritin 1 stimulates mitochondrial activity and promotes the expression of thermogenic genes.

To trigger its expression, the researchers used a viral vector that drives Neuritin 1 overexpression exclusively in thermogenic fat cells. The result was a sustained increase in metabolic activity, without affecting food consumption or physical activity in the animals.

“These findings point to Neuritin 1 as a promising therapeutic candidate for treating obesity and its associated conditions, such as type 2 diabetes and fatty liver disease, through a mechanism that differs from current approaches,” highlights Dr. Sánchez-Feutrie.

Relevance to human health

Beyond the animal model results, genetic data in humans also show a correlation between Neuritin 1 and susceptibility to obesity, reinforcing the potential relevance of the discovery. The team is currently exploring ways to translate these findings into a future therapeutic strategy.

The study was made possible thanks to the contributions of several IRB Barcelona core facilities, including Bioinformatics and Biostatistics, Functional Genomics, Protein Expression, and Histopathology. It also involved collaborators from international institutions such as the CNRS (France), Karolinska Institutet (Sweden), and the University of Houston (USA).

Kelli Lehto, Associate Professor of Neuropsychiatric Genomics at the University of Tartu, is leading a prestigious European Research Council (ERC) grant project that brings together genetics, psychology, and data science to investigate the causes of attention deficit hyperactivity disorder (ADHD) in adults and enhance diagnostic methods.

ADHD is a highly heritable neurodevelopmental condition, which has been primarily diagnosed in children and is characterised by impulsivity, hyperactivity and attention problems. Recently, an increasing number of adults are being diagnosed with ADHD. According to data from the Estonian Biobank over the past five years, the number of ADHD diagnosed among adults has multiplied. This trend is also confirmed by international studies.

According to Lehto, the rapid increase in the number of diagnoses suggests that symptoms characteristic of ADHD – such as restlessness and difficulties with concentration, planning, and completing tasks – are affecting a growing number of adults. While ADHD has been thoroughly studied in children, the causes and mechanisms behind the increasingly common adult ADHD remain unknown.

The situation is further complicated by the fact that, in adults, ADHD symptoms often significantly overlap with those of many other mental health issues, such as depression or anxiety. These problems can also arise due to environmental factors like fatigue and stress. “However, existing data suggest that ADHD is associated with a large number of specific gene variants, which are not yet used in diagnosis but could prove to be very helpful,” Lehto explained, referring to the issue that inspired her research project.

Genetics related to ADHD

Over the next five years, Lehto’s research group plans to investigate the causes of adult ADHD-related issues using genetic data alongside environmental and lifestyle information, including data on the use of smart devices. In addition to the University of Tartu Estonian Biobank, the analysis will also draw on data from biobanks in Norway, the Netherlands, Sweden, and the United Kingdom. The study will focus on the genetics of ADHD symptoms to determine which traits are most strongly linked to ADHD genetically, and which may stem from other factors.

Lehto acknowledges that the tools currently available to doctors do not allow for sufficiently accurate differentiation between mental health conditions.

Currently, no diagnostic biomarkers are used in psychiatry. All diagnoses are still based primarily on what the patient reports.”

Kelli Lehto, Associate Professor of Neuropsychiatric Genomics, University of Tartu

More accurate diagnostic methods

The ultimate goal of the project is to develop an innovative tool for more precise identification of adult ADHD. Using machine learning methods, the team will analyse questionnaire data on hundreds of mental health symptoms, lifestyle and personality traits to identify clusters of symptoms that are strongly associated with genetic risk for ADHD. Based on these findings, the research group aims to create a more accurate screening questionnaire that could help diagnose adult ADHD without the need for costly genetic testing. “This is where the innovation of our project lies. The result will be a novel biology-based assessment tool that will hopefully make it possible to more accurately identify adults who were not diagnosed with ADHD in childhood and who can finally receive the appropriate treatment for their lifelong problems. Even more importantly, this approach could also help to better identify other mental health conditions that are currently difficult to distinguish,” Lehto explained.

The research project has a budget of nearly €1.5 million, funded by the European Commission. European Research Council grants are among the most prestigious in the scientific world. The competition attracted over 3,928 proposals,12% of which were funded.

First-year undergraduates who grew up with overly cautious or controlling parents tend to experience increased anxiety when faced with stresses associated with the transition to university, researchers from McGill University and the University of California (Los Angeles) have found.

The researchers asked 240 first-year McGill students to fill out several questionnaires in the first six weeks of the fall semester. The questionnaires used well-established scales to measure the parenting style they were raised with, current anxiety symptoms and different types of stressors they encountered during the transition to university, including housing difficulties, personal loss or even life-threatening situations.

The team then looked at associations among those variables, focusing on how the relationship between exposure to stressors and current experiences of anxiety correlated with different parental behaviours.

“We found that students whose parents are very protective experience a stronger link between exposure to stressful events and feelings of anxiety,” explained Lidia Panier, the study’s lead author. Panier, a PhD student in the Department of Psychology, is a member of the Translational Research in Affect and Cognition (TRAC) Lab led by Professor Anna Weinberg, the study’s senior author and principal investigator.

While cautioning that their study model does not allow them to conclude that overprotective parenting causes anxiety in children, the researchers note that such a conclusion would be consistent with the existing body of research.

“Previous findings show that overprotective parenting leads to insecure attachment and poorer emotion regulation, both of which are linked to greater vulnerability to anxiety,” Panier said.

She said she believes overprotective parenting in childhood and adolescence may not be helpful in teaching kids how to adapt to stressful situations in the long term. At the same time, she noted that the overprotective parenting might in some cases be a response to a child’s anxious behaviours: parents might develop watchful attitudes or controlling habits to protect a child who often appears fearful.

“These interpretations are not mutually exclusive,” explained Panier. “A bi-directional dynamic where child behaviours influence parenting, which then affects child development, is also well-supported in the literature.”

The researcher said she hopes that future studies can clarify these links, as well as explore ways to better support young adults experiencing anxiety, especially during key transitional periods.

“It would be interesting to see if these patterns can change over time, such as whether supportive peer relationships in university can help young adults become more resilient, even if they experienced overprotective parenting,” she said.

About the study

“Parental overprotection moderates the association between recent stressor exposure and anxiety during the transition to university” by Lidia Panier et al. was published in Development and Psychopathology.

This research was supported by the Canada Research Chair in Clinical Neuroscience, the Canadian Institutes of Health Research (CIHR), the California Governor’s Office of Planning and Research/California Initiative to Advance Precision Medicine and the California Department of Health Care Services.