Category: 8. Health

A children’s hospital has been praised for its “strong leaders” and “compassionate staff”, as it is given an outstanding rating for its specialist community mental health services.

Liverpool’s Alder Hey Children’s Hospital, which was inspected by the Care Quality Commission (CQC) in March, was also commended for its work in schools, where it holds clinics for pupils.

The CQC said children “felt valued and listened to”.

Alder Hey provides specialist mental health, ADHD and autism spectrum disorder services for those aged up to 18.

The hospital’s mental services had been previously rated as good.

Alder Hey’s foundation trust said the upgrade reflected the “compassion, professionalism, and relentless commitment” of staff.

CQC inspectors said they found a dedication to giving children and young people a safe and caring service.

Inspectors found the services worked well with local schools to help deliver joined up and coordinated care.

Karen Knapton, from the CQC, said inspectors found “strong leaders, as well as kind and compassionate staff, who delivered high quality care”.

“Staff focused on what mattered to the people they were caring for, and as a result they felt valued and listened to.”

The overall rating for the trust remains unchanged and is rated as “Good”.

Following the detection of three new imported cases of chikungunya fever, Hong Kong’s Food and Environmental Hygiene Department (FEHD) conducted an anti-mosquito spray operation on Thursday in the hillside area opposite Lei Tung Estate, Ap Lei Chau.

The patients, who reside in Tsing Yi and Ap Lei Chau, had recently travelled to areas where chikungunya is prevalent, according to the Centre for Health Protection of the Department of Health. 

ALSO READ: Hong Kong records three imported chikungunya cases

Chikungunya fever is transmitted by Aedes mosquitoes and presents with fever, joint pain, and rash.

In coordination with the CHP, FEHD has strengthened mosquito control efforts, including fogging and larvicide application in high-risk areas. The public is advised to remove stagnant water and take protective measures against mosquito bites.

China Daily‘s Adam Lam took the photos on Thursday.

Overview

The compendium supports efforts to end mistreatment and achieve respectful maternal and newborn care, marking a decade since the WHO’s 2014 statement on the prevention of disrespect and abuse during facility-based childbirth. Despite substantial progress in understanding and measuring respectful care large-scale implementation remains limited. Emerging research has highlighted small-scale interventions, but there is still much to learn about the most effective approaches.

The purpose of the compendium is to consolidate key evidence, tools and
resources to support the practical implementation of respectful maternal and
newborn care across different contexts. It provides programme managers
with essential background to build a foundational understanding of mistreatment and respectful care. As such, it serves as a comprehensive resource
that integrates theory with practice.

Chemicals and reagents

Butylated hydroxytoluene (BHT, ≥ 98% purity, CAS 128-37-0) was obtained from Macklin. A stock solution of BHT was prepared at 10 mg/mL in dimethyl sulfoxide (DMSO, ≥ 99.5% purity, CAS 67-68-5) and stored at − 20 °C. Working solutions were freshly prepared by diluting the stock solution directly into the culture medium immediately before each experiment. Acridine orange (AO, ≥ 99% purity, CAS 65-61-2) was purchased from Solarbio (Beijing, China) and reconstituted into a working solution as per the manufacturer’s instructions.

Zebrafish husbandry and embryo collection

This work has received approval for research ethics from Laboratory Animal Welfare and Ethics Committee of Jinggangshan University (Medical Ethics Committee of Jinggangshan University) and a certificate of approval is available upon request. Wild-type adult zebrafish (AB) and the genetically modified strains used in this study include: The Tg(-2.4shha-ABC:GFP) line, in which the Hedgehog signaling target gene is specifically expressed with green fluorescent protein in hedgehog target cells; the Tg(olig2:DsRed) line, which marks motor neurons with red fluorescent protein; the Tg(elavl3:YC2) line, in which the neuron-specific green fluorescent protein is expressed in neuron cells; and the Tg(coro1a:EGFP) line, which specifically expresses green fluorescent protein in neutrophils and macrophages. All transgenic lines were obtained from the China Zebrafish Resource Center (Wuhan, China). Zebrafish were raised at 28 °C with the light/dark cycle of 14 h:10 h in an automatic circulation system. The dechlorinated water with the parameters of pH 6.9–7.2, hardness of 200 mg/L, dissolved oxygen concentration of 5–7 mg/L,and conductivity of 650 μS/cm was used for fish culture and exposure. Healthy embryos (5–6 hpf) were collected after natural mating (2 females:1–2 males) and fertilized eggs were transferred to a culture dish containing embryo culture medium (5 mM NaCl, 0.17 mM KCl, 0.33 mM CaCl₂, 0.33 mM MgSO₄)²².

BHT exposure and experimental design

Butylated hydroxytoluene (BHT) was dissolved at a concentration of 10 mg/ml in the culture medium as a reserve solution and stored at 4 °C. Then, 0.003% 1-phenyl-2-thiourea (PTU) was added to inhibit melanogenesis (the use of PTU is limited to experiments requiring fluorescence photography and staining). Zebrafish embryos were exposed to BHT at concentrations ranging from 1 to 28 mg/L. Based on preliminary dose-range finding experiments (1–28 mg/L), we determined the 72 hpf LC₅₀ (lethal concentration 50%) value to be 10.4 mg/L ((95% CI 9.931–11.07 mg/L, see Results Fig. 1E). Concurrent teratogenicity assessments across this concentration range established 3 mg/L as the lowest observed effect level, characterized by significant developmental abnormalities including body axis curvature. Furthermore, 7 mg/L, the highest concentration tested below the LC50, reproducibly induced severe teratogenic effects (e.g., high malformation rates) while maintaining survival rates adequate for detailed phenotypic analysis. Therefore, the final test concentrations were set to 3, 5, 7 mg/L, and 0.005% DMSO (control) to establish a clear dose–response relationship for BHT-induced developmental toxicity, particularly spinal defects. Healthy embryos (< 6 hpf) were transferred to 6-well plates containing BHT solutions, refreshed daily to maintain exposure stability and oxygenation. Developmental parameters (mortality, hatching rate, malformation rate) were recorded daily. After exposing embryos to designated BHT concentrations until 72 hpf, we anesthetized larvae with 200 mg/L tricaine and use 1% low melting point agar to solidify the embryo body position. We then captured malformation images using a stereomicroscope (V16, Germany) and performed two-dimensional fluorescence analysis via confocal microscopy (Leica TCS SP8, Germany), and the malformation status of each group of zebrafish was photographed. Heart rate (24, 48, 72 hpf), hatching rate (24, 48, 72 hpf), body curvature, length, and morphology (72 hpf) were quantified and three biological replicates²³. All methods were performed in accordance with the relevant guidelines and regulations and conform to the ARRIVE guidelines²⁴.

Larvae locomotor assay

Following treatment with BHT for each group of zebrafish up to 72 hpf, each concentration group selects 6 representative young zebrafish, placing the same concentration group on each row of the 24-well plate, and placing one juvenile fish in the corresponding position on the plate. Then, 2 mL of embryo culture medium was added, and the culture was continued until 120 hpf. The Noldus DanioVision system was used to monitor the zebrafish movement responses induced by BHT. The behavioral analysis was conducted under the following lighting conditions: Alternating light and dark cycles: 5 min of dark adaptation, 5 min of light exposure, 5 min of darkness, another 5 min of light exposure, a final 5 min of darkness. The average swimming speed of the zebrafish under different conditions was calculated, with each experiment being repeated at least three times. Locomotor activity, a key indicator of neurodevelopment, was monitored and analyzed²⁵.

Acridine orange (AO) staining

Apoptosis in larvae (72 hpf) was assessed using AO staining. Larvae were rinsed with PBS, incubated with AO working solution (5 µg/mL, diluted 1:2000) at 28.5 °C for 30 min in the dark, washed again, and imaged under a fluorescence microscope (DM IL, Leica, Germany).

Gene transcription analysis

Following treatment with the drug for 72 hpf, approximately 60–75 zebrafish, subjected to humane euthanasia, were collected from each group. Total RNA was extracted from the embryonic tissue homogenization of each group using the Tranzol UP Reagent (ET111-01, Japan Takara Company). Subsequently, approximately 1 µg of total RNA was reverse transcribed into cDNA using the cDNA Synthesis Kit (AE311-03, TRANS, China). qRT-PCR was performed on an ABI Step One Plus RT-PCR system (Applied Biosystems, Foster City, USA) using TransStart Green qPCR Supermix (AQ601-02, TRANS, China). The reaction conditions consisted of 10 min of pre-denaturation at 95 °C, followed by 40 cycles of 30 s of denaturation at 95 °C and 30 s of annealing at 60 °C. β-Actin gene was used as the internal reference, and the primer sequences are listed in Table S1. All expression levels of the relevant genes detected in this study can be found in the supplementary table S2. Each treatment group included three biological replicates.

Antibody staining

After BHT treatment at 72 h post-fertilization (hpf), the zebrafish embryos subjected to cryogenic euthanasia were first rinsed with phosphate buffer solution (PBS) three times (each for 5 min). They were then fixed with 4% paraformaldehyde (PFA) at 4 °C overnight. The following day, the samples were rinsed three times with 100% methanol before being treated with acetone at − 20 °C overnight. On the third day, the samples were dehydration with a gradient solution of 75% methanol + 25% PT (75 mL PBS + 25 mL Triton X-100), 50% methanol + 50% PT (50 mL PBS + 50 mL Triton X-100), and 25% methanol + 75% PT (25 mL PBS + 75 mL Triton X-100) for once, and then washed with PT solution three times, each for 5 min. To enhance the specific binding capacity of the antibodies, we stripped the epidermis from the back of the juvenile fish, and they were rinsed three times with 3% PT solution (97 mL PBS + 3 mL Triton X-100), each for 5 min. The samples were then incubated in PBTN solution (4% BSA, 0.02% NaN₃, 3% PT) at room temperature for 1 h, followed by overnight incubation with mouse monoclonal anti-α-Tubulin antibody (1:200, product number sc-23950, Santa Cruz Biotechnology) at 4 °C.

After labeling the primary antibody with Alexa Fluor 638 anti-rabbit IgG secondary antibody (1:1000, product number A-11004, American Invitrogen company), the samples were stained with freshly prepared PBS-DAPI solution (2 µg/mL) for 30 min. Finally, Images were acquired using a Leica TCS SP8 confocal laser scanning microscope. Z-stacks of optical sections were collected at intervals to encompass the relevant depth of the region of the spinal cord at specific somite levels. For visualization and presentation in the figures, maximum intensity projections (MIPs) of the Z-stacks were generated. Image analysis was performed on the using ImageJ software (version 1.49, National Institutes of Health, Bethesda, USA).

Rescue experiment

Smoothened agonist (SAG) is a commonly used activator of the Hedgehog signaling pathway (Hh), which specifically stimulates the key receptor Smoothened (SMO) in the Hh pathway²⁶. To investigate whether the body axis curvature induced by BHT exposure is due to abnormal induction of the Hh pathway, we co-exposed the animals to SAG and BHT. Rescue experiments were conducted with embryos fertilized for 6 h, including the following groups: DMSO control group, 7 mg/L BHT group, 3 mg/L SAG group, and 7 mg/L BHT + 3 mg/L SAG group. To ensure that the drug concentration in the solution in which the embryos were placed was always sufficient, the solution was changed every 24 hpf. After exposure for 72 hpf, the embryos were observed under a microscope to capture images. Developmental, behavioral, and gene expression endpoints were assessed as above.

Statistical analysis

Body length was measured using ImageJ software (Version 1.49, National Institutes of Health, Bethesda, USA), and the curvature of the body axis in brightfield images was assessed. At 48 and 72 hpf, zebrafish embryos were placed under a body-vision microscope (Leica TCS SP8) and the heart rate was recorded for 20 s. A complete heartbeat was defined as a continuous mechanical fluctuation from the onset of atrial contraction to the end of ventricular contraction. Five embryos within each concentration group were randomly selected for counting and repeated three times in parallel. Data were analyzed using GraphPad Prism 8 and the normality of the data (Each data point represents data relating to larvae in an independent experimental replicate, each treatment contained three biological replicates) was evaluated using the Shapiro–Wilk test. The results showed that the data conform to the normality assumption. Therefore, parametric statistical tests were used and one-way ANOVA and Student’s t-test were used to identify significant differences. Unless otherwise stated, statistical significance was indicated as *p < 0.05, **p < 0.01, ***p < 0.001, and ****p < 0.0001 compared to the blank controls.

On August 5, the US Department of Health and Human Services announced that HHS Secretary Robert F. Kennedy Jr. has canceled nearly $500 million in grants and 22 federal contracts for developing mRNA vaccines, effectively halting the government’s investment in one of the most transformative medical technologies of the 21st century. The decision, part of what HHS called a “coordinated wind-down” under the Biomedical Advanced Research and Development Authority (BARDA), terminates or restructures dozens of vaccine projects with companies and institutions such as Pfizer, Moderna, Sanofi and Emory University.

According to the communication issued by Kennedy,“We reviewed the science, listened to the experts, and acted. Biomedical Advanced Research and Development Authority (BARDA) is terminating 22 mRNA vaccine development investments because the data show these vaccines fail to protect effectively against upper respiratory infections like COVID and flu.”

Kennedy’s statements, in line with his rabid anti-vaccine stance, are patently false and will have potentially lethal consequences as it further undermines the ability for the world to develop targeted vaccines when another epidemic emerges, when time is of the essence for producing these treatments and getting shots in arms.

The decision has triggered a wave of alarm from scientists and public health leaders. Experts warn that dismantling mRNA development efforts could compromise pandemic preparedness and biomedical progress. Epidemiologist Michael Osterholm called it “the most dangerous decision in public health” he’s seen in five decades, warning that it will slow the rapid vaccine deployment needed in future outbreaks.

2023 Nobel laureate Katalin Karikó, whose work laid the foundation for mRNA technology, said Kennedy’s reasoning was “false based on false information,” and warned that the global scientific progress made in vaccine development has been “tremendously” set back. Former BARDA director Rick Bright likened the decision to “disbanding the fire department because the fire’s out,” calling it a “strategic failure” that could cost lives in the next crisis.

It bears reviewing the critical contributions COVID-19 vaccines, particularly the mRNA vaccines, have made during the ongoing pandemic, which have been estimated to have saved millions of lives globally.

To our immune system, naked RNA is a sign of a viral or bacterial invasion and must be attacked. But our own cells also have RNA. To ward off trouble, our cells clothe their RNA in sugars, Vijay Rathinam and colleagues in the UConn School of Medicine and Ryan Flynn at Boston Children’s Hospital report on Aug. 6 in Nature.

Ribonucleic acid (RNA) is a family of large biological molecules fundamental to all forms of life, including viruses, bacteria, and animals. Viruses as diverse as measles, influenza, SARS-CoV-2, and rabies all have RNA, which is why the immune system starts attacking when it sees RNA in the bloodstream or in other inappropriate locations. But our own cells have RNA as well, sometimes displaying it on their surface, plain for roaming immune cells to see – and yet the immune system ignores it.

“Recognizing RNA as a sign of infection is problematic, as every single cell in our body has RNA,” says UConn School of Medicine immunologist Vijay Rathinam. The question is, how does our immune system distinguish our own RNA from that of dangerous invaders?

Previous research led by Boston Children’s Hospital and Stanford University researchers Ryan Flynn and Carolyn Bertozzi had noticed that our bodies add sugars onto RNA. These sugarcoated RNAs (also known as glycosylated RNAs, or glycoRNAs) are displayed on the cell surface and don’t seem to provoke the immune system.

Rathinam and his colleagues wondered whether the sugar was somehow shielding the glycoRNAs from the immune system. This could be a strategy the body uses to prevent our own RNA from provoking inflammation.

When Vincent Graziano, a Ph.D. student in Rathinam’s lab and lead author on the paper, took glycoRNA from human cell cultures and blood, cut off the sugars, and reintroduced it into cells, the immune cells attacked it. The immune cells had ignored the same RNA when it was sugarcoated.

The sugarcoating hides our own RNA from the immune system.”

Vijay Rathinam, immunologist, UConn School of Medicine

It is particularly significant to our body because cells are often covered by glycoRNAs. When cells die and are cleaned up by the immune system, the sugarcoating of RNA prevents dead cells from unnecessarily stimulating inflammation.

The findings could help when thinking about autoimmune diseases. Certain autoimmune diseases, such as lupus, are associated with specific RNA and dead cells setting off the immune system. Now that scientists understand the role of RNA glycosylation in deflecting immune system attention, they can check on whether that strategy is somehow going awry, and, if so, how it might be fixed.

This study was done in collaboration with the laboratories of Ryan Flynn, Thomas Carell, Franck Barrat, Beiyan Zhou, Sivapriya Kailasan Vanaja, Michael Wilson, and Penghua Wang and was funded by grants from the National Institutes of Health.

A group led by the Department of Cell Biology at the Kidney Research Center, Niigata University revealed that elevated activity of cdc42 is a critical initiation event leading to proteinuria, and proposed that suppression of cdc42 activity could be a promising therapy for nephrotic syndrome.

Glomerulus is a filtration unit of the kidney, and the glomerular capillary wall functions as a barrier, preventing the leak of plasma protein into urine. Proteinuria is a clinical symptom showing dysfunction of the barrier of glomerular capillary wall, and is an aggravating factor leading to kidney failure. Besides, proteinuria is reported to be a risk factor for cardiovascular and cerebrovascular diseases. Glomerular epithelial cell (podocyte) is located in outer layer of glomerular capillary wall, and possesses unique processes named foot processes. Neighboring foot processes are bridged by slit diaphragm. It is accepted that slit diaphragm functions as a final barrier preventing proteinuria. Recent clinical studies reported that the major parts of nephrotic syndrome are caused by autoantibody against nephrin, a key component of slit diaphragm.

A group at Niigata University analyzed signaling pathways in podocyte after stimulation by anti-nephrin antibody. The study revealed that ephrin-B1 at slit diaphragm interacted with nephrin and Par6, and that the anti-nephrin antibody caused the phosphorylations of nephrin and ephrin-B1 in a Ca²⁺ influx–dependent manner. Phosphorylated ephrin-B1 was dissociated from nephrin and also from Par6, and Par6 came to interact with cdc42. The binding of Par6 promoted cdc42 activity. Elevated cdc42 activity promoted calcineurin activity, activated Snail, a transcription factor, and decreased mRNA expression of nephrin, ephrin-B1 and other functional molecules of slit diaphragm (cf. Image). The altered expression of the functional molecules induced the loss of barrier function of slit diaphragm, which leads to proteinuria. The study also showed that a cdc42 inhibitor restored the expression of slit diaphragm functional molecules. Researchers argued that the regulation of cdc42 activity could be a promising therapy for nephrotic syndrome.

High blood pressure, aka hypertension, is known to increase the risk of cardiovascular disease. And the best way to prevent or rather manage (along with the prescribed meds) it, is exercise, particularly walking. A recent study found that walking can be beneficial in reducing the risk of heart attacks, heart failure, and stroke in people with high blood pressure. A new study found that you don’t necessarily need to walk 10,000 steps to reduce the risk of heart diseases, even fewer steps count. The findings of the study are published in the European Journal of Preventive Cardiology.

10,000 steps is not the gold standard of walking

Approximately 1.28 billion people worldwide are living with high blood pressure, which increases the risk of heart disease (49% increase), stroke (62% increase), and heart failure (77-89% increase). Until now, it was unclear how much physical activity is required to reduce the risk of major adverse cardiovascular events (MACE).The researchers analyzed over 36,000 people with high blood pressure and found that taking more steps, and walking faster, even though it’s below the recommended daily target of 10,000, can have a significant reduction in the risk of cardiovascular diseases.

The study found that every extra 1,000 steps after 2,300 steps was linked to a 17% reduction in the risk of developing a MACE. The benefits increased up to 10,000 steps. After 10,000, there was a significant reduction in the risk of stroke.“This study is one of the first to demonstrate a dose-response relationship between daily step count and major problems of the heart and blood vessels. In a nutshell, we found that, if you live with high blood pressure, the more you walk with greater intensity, the lower your risk for future serious cardiovascular events. These findings support the message that any amount of physical activity is beneficial, even below the widely recommended daily target of 10,000 steps,” Professor Emmanuel Stamatakis, Director of the Mackenzie Wearables Research Hub at the University of Sydney, Australia, who supervised the study, said, in a statement.

Findings

They found that there was a 17% reduction in overall risk for every extra 1,000 steps a day, and a 22% reduction in heart failure, 9% reduction in risk of heart attack, and a 24% reduction in risk of stroke. This means that every increase of 1,000 steps a day was associated with:

If a person walks for 30 minutes at a fast pace, the average (mean intensity) is 80 steps per minute. This was associated with a 30% reduced risk of MACE. There was no evidence of harm in people whose 30 minutes of fastest walking or running was over 130 steps a minute.

They found that every 1,000-step increase in daily step count led to an average lower risk of MACE, heart failure, myocardial infarctions, and stroke of 20.2%, 23.2%, 17.9%, and 24.6%, respectively.“Our findings offer patients accessible and measurable targets for heart health, even below 10,000 steps daily. Clinicians should promote physical activity as standard care, especially in patients with high blood pressure. Our results can inform new, tailored public health recommendations for these patients. Future recommendations on walking in people with high blood pressure could consider promoting higher stepping intensity,” Prof. Stamatakis added.

COVID-19 prevention methods such as masking and social distancing also suppressed the circulation of common respiratory diseases, leaving young children lacking immunity to pathogens they otherwise would have been exposed to, a new multi-center clinical research study reveals. The investigators say their findings help explain the large post-pandemic rebound in these diseases and enable more accurate predictions for the future.

The study, published Aug. 6 in The Lancet Infectious Diseases and funded by the National Institutes of Health, followed 174 children under the age of 10 from 2022-2023 across four academic medical centers across the country: Weill Cornell Medicine; University of Colorado Anschutz Medical Campus and Children’s Hospital Colorado; University of North Carolina; and the University of Alabama at Birmingham. Through repeat blood sampling and respiratory sampling during illness, the investigators gauged the children’s level of immunity to many common and emerging respiratory viruses, such as RSV, influenza and enterovirus D68 (EV-D68), which can cause the polio-like illness acute flaccid myelitis.

The findings, among the first from the National Institutes of Health’s PREMISE (Pandemic Response Repository through Microbial and Immune Surveillance and Epidemiology) Program, showed that most young children lacked immunity to many normal respiratory viruses during the pandemic, suggesting they had not been exposed, as they typically would have, due to prevention measures in place. Enrolled children received routine medical care while participating in the observational study. Following the lifting of pandemic measures, the level of immunity rose across all pathogens studied, reflective of the unprecedented widespread resurgence of these viruses in children post-pandemic.

PREMISE is a one-of-a-kind study as we followed very young children, with their parents’ consent, over a year for longitudinal sample collection, affording us the unique opportunity to assess immunity due to primary infection, re-exposure and even vaccination, during a time when mask requirements and other non-pharmaceutical interventions were lifted.”

Dr. Perdita Permaul, co-first author, section chief of pediatric allergy and immunology, associate professor of clinical pediatrics and trial principal investigator at Weill Cornell Medicine

The data allowed experts to recreate past circulation patterns and model predictions for future outbreaks with greater accuracy and precision. They showed that PREMISE data from 2022-23 could be used to accurately predict the subsequent wave of disease of the emerging pathogen EV-D68 that occurred in 2024.

“Findings from our study successfully demonstrate the utility of longitudinal immunologic surveillance in children, particularly young, immunologically naïve unexposed children, to help model the behavior of endemic viruses,” said Dr. Permaul, who is also an Englander Clinical Scholar at Weill Cornell Medicine and a pediatric allergist and immunologist at NewYork-Presbyterian Komansky Children’s Hospital of Children’s Hospital of New York.

Investigators have so far evaluated nearly 1,000 children through PREMISE, based at NIH’s Vaccine Research Center, providing a treasure-trove of sampling and data that can be used to learn which parts of viruses the human immune system attacks to develop immunity. This information may enable teams to better design new antibody treatments and effective vaccines to mimic this response.

“This approach allows for the rapid development of vaccine and monoclonal antibody therapeutics for pathogens of interest in children,” Dr. Permaul said. “Future analysis of blood samples collected from almost 1,000 children enrolled in PREMISE includes pathogen-specific T and B cell responses. Longitudinal immune surveillance in young children is an important tool for informing public health planning, assessing the effectiveness of pharmacologic and non-pharmacological interventions, developing ‘on the shelf’ therapeutics and mitigating overall disease burden.”

This study is fully funded by a subcontract with Frederick National Laboratory for Cancer Research (FNLCR), currently operated by Leidos Biomedical Research, Inc. through Agreement 21X192QT1. FNLCR funding was provided by the NIH Vaccine Research Center. The total project funding is $7.98 million over five years.  No financing for this project is supplied by nongovernmental sources.