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  • Can heart attack lead to vision loss? Research reveals the hidden impact of heart disease |

    Can heart attack lead to vision loss? Research reveals the hidden impact of heart disease |

    Heart attacks, medically known as acute myocardial infarctions, primarily affect the heart but can also have unexpected effects on other parts of the body, including the eyes. The research “Comorbid vision and cognitive impairments in older adults hospitalized for acute myocardial infarction” highlights that many older adults who suffer heart attacks also experience vision problems, not necessarily caused directly by the heart attack itself, but linked through shared vascular health issues. Poor blood flow, inflammation, and damaged blood vessels can impact the retina—the light-sensitive tissue in the eye—leading to blurred vision, temporary vision loss, or more serious eye conditions related to heart disease. Emerging evidence shows that vision impairment in heart attack patients is common and is associated with worse health outcomes, underscoring the importance of eye health in cardiovascular care.

    The link between heart attack and vision loss

    Vision and heart health are closely intertwined because the eyes rely on a dense network of tiny blood vessels to receive oxygen and nutrients. Cardiovascular conditions such as heart attacks can impair this blood flow. Studies demonstrate that vascular disease weakens or blocks these vessels, increasing the risk of retinal damage that may lead to vision impairment or loss. Research from top medical centers indicates that specific eye diseases, like a form of age-related macular degeneration (AMD), are strongly linked to underlying heart and vascular problems.

    Common vascular risk factors affect both heart and eyes

    Older adults experiencing heart attacks frequently have other health challenges such as hypertension, diabetes, and high cholesterol. These vascular risk factors simultaneously affect the heart and the blood vessels supplying the eyes. A large U.S. study of seniors over 75 found that over one-third of patients hospitalized for heart attacks had vision impairment. Furthermore, those with both vision and cognitive impairments faced higher risks of death and functional decline after the heart attack.

    Vision problems may signal underlying heart disease

    Eye doctors can spot early warning signs of heart disease during routine eye exams by observing changes in retinal blood vessels. Conditions such as retinal artery occlusion or ocular strokes can indicate an increased risk of heart attack or stroke. This makes vision health a critical component in detecting and managing cardiovascular risk.

    Managing vision health alongside heart care

    For individuals recovering from a heart attack, monitoring vision health can help prevent further complications. Addressing vision issues and controlling vascular risk factors through proper medication, lifestyle changes, and regular eye check-ups can improve overall outcomes. The research underscores that vision impairment should not be overlooked in cardiac care, especially in older patients.


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  • ‘The Book of Sheen’ by Charlie Sheen review – The Washington Post

    1. ‘The Book of Sheen’ by Charlie Sheen review  The Washington Post
    2. Charlie Sheen Opens Up About Sexual Encounters with Men in Memoir and New Doc  People.com
    3. Charlie Sheen admits he was a sex addict, says he was extorted by partners  ABC News
    4. ‘The Conjuring: Last Rites’ Makes History at the Box Office  The Daily Beast
    5. aka Charlie Sheen OTT release date in India, what to expect, trailer breakdown, and more about the Hollywood star’s documentary  OTTPlay

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  • Ascletis Announces Ultra-Long-Acting Subcutaneous Depot Maintenance Formulation of Small Molecule GLP-1R Agonist ASC30 Demonstrated an Observed Half-Life of 75 Days in Participants with Obesity

    –          Maintenance formulation of small molecule ASC30 demonstrated an observed half-life of 75 days in participants with obesity in the U.S. Phase Ib study.

    –          75-day observed half-life supports once-quarterly administration.

    –          Once-quarterly SQ administration of ASC30 is the most clinically advanced once-quarterly incretin drug and has the potential to address a highly unmet need as a maintenance therapy for chronic weight management, representing a significant patient population. 

    HONG KONG, Sept. 9, 2025 /PRNewswire/ — Ascletis Pharma Inc. (HKEX: 1672, “Ascletis”) announces today that ultra-long-acting subcutaneous (SQ) depot maintenance formulation of small molecule GLP-1 receptor (GLP-1R) agonist ASC30 demonstrated an observed half-life of 75 days in participants with obesity (body mass index (BMI) ≥ 30 kg/m2) in a U.S. Phase Ib clinical study (NCT06679959), supporting once-quarterly administration as a maintenance therapy for chronic weight management. The ASC30 maintenance formulation was developed utilizing Ascletis’ Ultra-Long-Acting Platform (ULAP).

    After a single SQ injection of ASC30 (100 mg) maintenance formulation in eight participants with obesity, the median time for ASC30 to reach maximum concentrations (Cmax) was 17 days post-dose. The time for ASC30 concentrations to reduce to fifty percent (50%) of ASC30’s Cmax was approximately 75 days post-dose, demonstrating an observed half-life of 75 days.

    “Maintenance therapy represents a significant unmet medical need for chronic weight management,” said Jinzi Jason Wu, Ph.D., Founder, Chairman and CEO of Ascletis. “For example, after a period of treatment with once-weekly administered incretin drugs that help reach weight loss goals, patients prefer to switch to a once-quarterly therapy to maintain the weight. Based on its promising pharmacokinetic parameters, including the ultra-long half-life, and good safety, we believe once-quarterly administration of ASC30 has the potential to help patients maintain their weight without rebound. Ultra-long-acting SQ depot maintenance formulation of ASC30 represents the most clinically advanced once-quarterly incretin drug and a potential major breakthrough in providing once-quarterly maintenance therapy for patients on chronic weight management, potentially enhancing compliance and quality of life.” 

    Tolerability is key to maintenance therapies. During the 12-week period after a single SQ injection of ASC30 (100 mg) maintenance formulation, incidence rates of vomiting, nausea, diarrhea and constipation in ASC30-treated patients (N=8) were 0.0%, 0.0%, 12.5% and 12.5%, respectively, compared to 0.0%, 12.5%, 6.3% and 0.0%, in placebo-treated patients (N=16). The favorable gastrointestinal (GI) tolerability of ASC30 maintenance formulation resulted from the slow rate of rise to Cmax and peak-to-trough (Cmax-to-Ctrough) ratio of approximately 2.5:1 during 12-week period post-dose. The trough concentrations (Ctrough) of ASC30 were reached 84 days post-dose.

    In the Phase Ib study, no serious adverse events (SAEs) were reported. There were no Grade 3 or higher adverse events (AEs) observed. GI-related AEs were rare and only Grade 1 among 100 mg ASC30 treated participants with obesity. There were no elevations of liver enzymes including alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBL). There were no abnormal findings in laboratory tests, vital signs, ECGs (electrocardiograms, including QTc intervals), and physical exams. Table 1 summarizes the safety and tolerability profile of 100 mg ASC30 compared to placebo.

    Table 1. Safety and tolerability profile of 100 mg ASC30 compared to placebo

    Category

    ASC30 maintenance

    formulation

    100 mg

    (N=8)

    n (%)

    Placebo

    (N=16)

    n (%)

    Number of participants reporting at least one

    TEAE

    8 (100 %)

    14 (87.5 %)

    Number of participants reporting TEAEs by severity

        Grade 1

    7 (87.5 %)

    12 (75.0 %)

        Grade 2

    1 (12.5 %)

    2 (12.5 %)

        Grade 3

    0 (0.0 %)

    0 (0.0 %)

        Grade 4

    0 (0.0 %)

    0 (0.0 %)

    Number of participants reporting SAEs

    0 (0.0 %)

    0 (0.0 %)

    Overall discontinuation

    0 (0.0 %)

    0 (0.0 %)

    Common GI-related TEAEs

        Vomiting

    0 (0.0 %)

    0 (0.0 %)

        Nausea

    0 (0.0 %)

    2 (12.5 %)

        Diarrhea

    1 (12.5 %)

    1 (6.3 %)

        Constipation

    1 (12.5 %)

    0 (0.0 %)

        Abdominal pain

    0 (0.0 %)

    0 (0.0 %)

    Notes: TEAE(s): treatment-emergent adverse event (s); SAEs: serious adverse events; GI: gastrointestinal.

    The clinical trial design including ASC30 maintenance dose selection is currently being evaluated including consultation with the regulatory authorities.

    ASC30 ultra-long-acting SQ depot formulations demonstrated dose-proportional pharmacokinetic profiles that support both treatment and maintenance therapies. As previously announced, ASC30 ultra-long-acting SQ depot treatment formulation, also developed utilizing Ascletis’ ULAP, is being investigated as a once-monthly treatment therapy in a Phase IIa study (NCT06679959) in the U.S. in participants with obesity (BMI ≥ 30 kg/m2) or overweight (BMI ≥ 27 kg/m2 but < 30 kg/m2) with at least one weight-related comorbidity (Press Release). Topline data of ASC30 treatment formulation of Phase IIa study are expected in the first quarter of 2026. ASC30 treatment formulation demonstrated an observed half-life of 46 days in participants with obesity, supporting once-monthly administration to treat obesity.

    Based on the properties of small molecules, peptides and proteins/antibodies, Ascletis can design, through its proprietary ULAP technology, various release constants (k) of drugs in SQ depots to precisely release SQ injected drugs slowly over desired dosing intervals to reduce peak-to-trough ratios and improve clinical outcomes.

    ASC30 was discovered and developed in-house at Ascletis as a first and only investigational small molecule GLP-1R biased agonist designed to be administered once daily orally and once monthly to once quarterly subcutaneously as a treatment therapy and a maintenance therapy for chronic weight management.

    About ASC30

    ASC30 is an investigational GLP-1R biased small molecule agonist and has unique and differentiated properties that enable the same small molecule for both oral tablet and subcutaneous injection administrations. ASC30 is a new chemical entity (NCE), with U.S. and global compound patent protection until 2044 without patent extensions. 

    About Ascletis Pharma Inc.

    Ascletis Pharma Inc. is a fully integrated biotechnology company focused on the development and commercialization of potential best-in-class and first-in-class therapeutics to treat metabolic diseases. Utilizing its proprietary Artificial Intelligence-Assisted Structure-Based Drug Discovery (AISBDD) Platform and Ultra-Long-Acting Platform (ULAP), Ascletis has developed multiple drug candidates in-house, including its lead program, ASC30, a small molecule GLP-1R agonist designed to be administered once daily orally and once monthly to once quarterly subcutaneously as a treatment therapy and a maintenance therapy for chronic weight management. Ascletis is listed on the Hong Kong Stock Exchange (1672.HK).

    To learn more about Ascletis, please visit www.ascletis.com.

    Contact：

    Peter Vozzo
    ICR Healthcare
    443-231-0505 (U.S.)
    [email protected]

    Ascletis Pharma Inc. PR and IR teams
    +86-181-0650-9129 (China)
    [email protected]
    [email protected]

    SOURCE Ascletis Pharma Inc.

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  • 25 years of Virgin Australia: the story of the fastest growing Virgin company of all time

    25 years of Virgin Australia: the story of the fastest growing Virgin company of all time

    Brisbane to Sydney. August 31, 2000.

    Virgin Australia (then called Virgin Blue) took to the skies for the very first time. 25 years on, and the airline is soaring higher than ever – having flown more than 200 million guests across the clouds. Here’s a closer look at the fastest growing Virgin company of all time…

    The spark for an Australian airline came from unusual circumstances. Richard Branson was in the pub with Brett Godfrey, who scribbled down the details on a beer mat. Brett was the chief financial officer for Virgin Express, which was our European carrier in the 90s and 00s.

    In that moment, people were being ripped off by the duopoly that Qantas and Ansett had on the market. Forever intrigued by a David vs Goliath story, Richard and Brett began brainstorming ways to bring a low-cost carrier model to Australia. Richard said, ‘screw it, let’s do it’, and things moved fast.

    Following in Virgin Atlantic’s footsteps – the airline started small with just two aircraft flying between Brisbane and Sydney. Through consistent innovation, a cheeky attitude, competitive spirit, and that intangible Virgin magic – Virgin Blue evolved into Virgin Australia, and into Australia’s largest carrier (by domestic market share).

    As with all Virgin companies, it’s the people who set the brand apart. Indeed, the first Virgin Blue job ad said: “If you’ve got purple hair and you’re working in a butcher’s shop and you can still smile after a tough day, you’re the kind of cabin crew we’re looking for…”

    That attitude has held its own for 25 years now. In fact, some of Virgin Australia’s team members have been with us since day dot. Meet Julie, Jack & Shane (a father and son duo), Rob, Kellie, Nicole, Stu, and Carmello – each with their own story, memories, and dedication that have helped make Virgin Australia what it is today.

    Being a force for good in the world has been essential for Virgin Australia. Take its partnership with the Starlight Children’s Foundation for example. 15 years in and Virgin Australia has granted the wishes of 3,000 seriously ill children – sprinkling magic where it’s needed most.

    Just like its counterpart in the Atlantic, Virgin Australia has a restless spirit for innovation, challenging the status quo, and never resting on its laurels. It’s investing $400 million into transforming its operations, upgrading its fleet, introducing more fuel-efficient aircrafts such as the Embraer E190‑E2 jets, expanding its network, reestablishing its long-haul presence through its partnership with Qatar Airways, and – most importantly – will soon become the first Australian carrier to allow pets on-board.

    And let’s not forget loyalty. Virgin Australia’s Velocity Frequent Flyer program has more than 13 million members, and they are constantly raising the bar of what a loyalty program looks like.

    25 years on, and Virgin Australia continues to make the skies just that little bit more wonderful.

    Check them out.

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  • Apple’s new iPhone launch comes amid Trump-era trade war concerns – NBC New York

    Apple’s new iPhone launch comes amid Trump-era trade war concerns – NBC New York

    Apple on Tuesday will unveil its next line-up of iPhones amid a global trade war that’s added a potential price increase to the usual intrigue surrounding the annual evolution of the company’s marquee product.

    The new iPhones will be the first to be released since President Donald Trump returned to the White House and unleashed a barrage of tariffs, in what his administration says is an attempt to bring overseas manufacturing back to the U.S. — a crusade that has thrust Apple CEO Tim Cook into the hot seat.

    If Apple follows the same naming scheme since the product’s 2007 debut, the new models will be called the iPhone 17. But the Cupertino, California, company recently deviated from tradition with its naming formula for the iPhone operating system. When the next version of its iOS system was previewed at its developers conference in June, Apple revealed the free update will be called iOS 26 in reference to the upcoming year — a marketing technique that automakers have embraced for decades.

    Regardless, these new iPhones are still expected to be made in Apple’s manufacturing hubs in China and India, much to the Trump administration’s consternation.

    Both Trump and U.S. Commerce Secretary Howard Lutnick have repeatedly insisted that iPhones be made in the U.S. instead of overseas. It’s an unrealistic demand that analysts say would take years to pull off and would result in a doubling, or even a tripling, of the iPhone’s current average price of about $1,000.

    Cook tried to placate Trump by initially pledging that Apple would invest $500 billion i n the U.S. over the next four years, and then upped the ante last month by adding another $100 billion to the commitment. He also gifted Trump a statue featuring a 24-karat gold base.

    That kind of diplomacy has helped insulate Apple from Trump’s most severe tariffs. However, the iPhones being brought into the U.S. still face duties of about 25%, stoking speculation that the company will reveal its first across-the-board price increase in five years in an effort to preserve its hefty profit margins.

    Since 2020, Apple has charged $800 for its basic iPhone and $1,200 for its top offering, but analysts now believe the company may raise prices by $50 to $100 on some of the new models. If Apple does announce price increases, it will come just weeks after Google held steady on prices for its new Pixel smartphones.

    Whatever Apple ends up charging for the next iPhone, the new line-up isn’t expected to be much different from last year’s model — the first to be designed for a wide range of new artificial intelligence features. While the iPhone 16 has proven to be popular, the models didn’t sell quite as well as analysts had anticipated because Apple failed to deliver all the AI-fueled improvements it had promised, including a smarter and more versatile Siri assistant. The Siri improvements have been pushed back until next year.

    That has lowered the expectations for this year’s line-up, which will likely include the usual improvements in camera quality and battery life on top of a slightly redesigned appearance. The most significant new twist could be the introduction of an ultra-thin iPhone dubbed “Air” — a moniker Apple already slaps on like its sleekest iPads and Mac computers.

    The relatively minor updates to recent iPhone models are raising questions about Apple’s ability to innovate in the fast-moving era of AI, said Forrester Research analyst Thomas Husson. “Apple is reaching a tipping point, and I expect 2026 and 2027 to be pivotal years.”

    Apple’s AI follies, combined with its exposure in Trump’s trade war, have weighed on the company’s stock, while the market values of Big Tech peers like Microsoft, Nvidia, Meta Platforms and Google parent Alphabet have been surging.

    Although Apple’s stock price is still down by 4% so far this year, the shares have been bouncing back in recent months amid signs it won’t be as hard hit by the tariffs as once feared, and a highly anticipated court ruling cleared the way for the company to continue receiving $20 billion annually to lock in Google’s search engine as the default option on iPhones.

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  • Maria B says was ‘exercising right to free speech’ in reply to NCCIA in trans community defamation case – Culture

    Maria B says was ‘exercising right to free speech’ in reply to NCCIA in trans community defamation case – Culture

    Designer Maria Butt — known more popularly as Maria B — has submitted her defence to the National Cyber Crime Investigation Agency (NCCIA) in a complaint made in August relating to the designer’s anti-transgender rhetoric on social media. The complaint was filed against her by Saima Butt for defaming the transgender community.

    The designer had designated her lawyer to appear before the NCCIA on September 2. In the response submitted by Barrister Mian Ali Ashfaq on behalf of Maria B, a copy of which is available with Images, she claimed she was exercising her right to free speech and expression under Article 19 of the Constitution. The response states that the designer was expressing “reasonable opinions on matters of public concern” and that her post was made “within the ambit of lawful expression” and in “good faith and for the larger public good”.

    The response argues that, because the people in the video the designer posted were hardly visible and wearing masks, her post can not be taken as defamation against any individual. The complaint, Maria B’s statement claimed, was made with “malicious intent” to harass her.

    The Lahore police booked around 60 transgender persons and others in August and arrested some of them for allegedly organising an “objectionable” private party after Maria B uploaded photos and videos of it on her social media accounts. Later, a magistrate dismissed the case against the transgender persons after no incriminating material was found connecting them with the commission of the alleged offences.

    She had posted videos on her social media accounts, demanding action against “transgender activists” that she claimed featured in the clips, terming such gatherings “against the moral values of the country”.

    This is not the first time the designer has made anti-trans remarks on her social media accounts. Recently, she celebrated the banning of a screening of Joyland in Lahore, describing it as a “shameful transgender satanic show”. Joyland is a film and was Pakistan’s official Oscars submission for the year 2023.


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  • Psychometric properties of the ethical safety questionnaire in acute healthcare environments – a cross-sectional study | BMC Medical Ethics

    Psychometric properties of the ethical safety questionnaire in acute healthcare environments – a cross-sectional study | BMC Medical Ethics

    Research design

    The validation of the ESQ was carried out through a descriptive cross-sectional design study, where a purposive sampling was employed across the nursing and physiotherapy workforce in the four countries which participated in this study. Participants were recruited through intermediaries within one acute hospital in each partner country. These hospitals were selected based on their affiliation with the respective educational institutions. Participation in this research study was voluntary and anonymous. Data was collected from June 2023 to August 2023 via Webropol 3.0 in hospitals in Finland, Sweden, Latvia, and Malta.

    Participants and research context

    Study population

    The study population consisted of a total of 275 nurses and physiotherapists at four major hospitals in Finland, Sweden, Latvia, and Malta.

    Inclusion and exclusion criteria

    Nurses and physiotherapists in acute healthcare environments with permanent employment, both part-time and full-time, were eligible to participate in the present study. Healthcare professionals were included regardless of minimum work experience. Students and agency hired staff or temporary workers were excluded.

    Study contexts and recruitment procedure

    Four major hospitals in Finland, Sweden, Latvia, and Malta were chosen for data collection. All hospitals were urban-based and nurses and physiotherapists working in acute care were invited to participate. Health professionals from non-acute settings were excluded. Purposive sampling was used to obtain the required sample across the four study settings. The hospitals involved in recruitment were all teaching hospitals affiliated with the educational entities conducting this research study. The respective management of the hospitals were informed about the study, and permissions were obtained to conduct the data collection. The researchers from each of the four countries, thereafter, introduced the study to the managers of the respective hospitals in the associated country and these managers acted as intermediaries by distributing the Webropol link to the questionnaire to all nurses/physiotherapists working at the hospital. Every participant received a link to the questionnaire with a cover letter informing participants about the aim and purpose of the study. The letter explained that participation entails the completion of a questionnaire (the ESQ) and it emphasised voluntary participation and assured anonymity in relation to participation. Completion of the questionnaire via Webropol implied a respondent’s consent to participate. A reminder to fill out the questionnaire was sent twice at two-week intervals.

    Sample size

    Purposive sampling was used to obtain the required sample over 200 participants completed the questionnaires. This sample size complies with validation studies standards ranging from 100 to 400 [12].

    Data collection and instrument

    Data collection tool

    In this study, the ESQ was used [4]. Permission to translate and use the tool was granted by the developer, Tarja Poikkeus (also co-author of the present manuscript). The ESQ contains 11 items. Two items are general ethical safety statements and there are three subscales: ethical autonomy, ethical respect, and ethical confidence. The ESQ uses a 5-point Likert scale where 1 represents ‘strongly disagree’ up to 5 ‘strongly agree’. The three subscales all contain three items each. Higher scores on each ESQ subscale (Ethical Autonomy, Ethical Respect, and Ethical Trust) reflect stronger perceptions of ethical safety in the healthcare work environment.

    Cross-cultural adaptation and face validity

    The original ESQ in Finnish, was translated according to translation unit standards [13]. The forward translations (Finnish to English, Swedish, and Latvian) were completed by three translators who were fluent native speakers of the respective languages. This was followed by a reconciled translation based on the three translations; a third person, reviewed the translations and combined them into one reconciled ESQ. The reconciled ESQ-translated versions were back-translated into Finnish by two independent persons, for the respective language, who were fluent in English, Swedish and Latvian. The results of all steps (i.e., two forward translations, reconciliation, and two backward translations with comments) were proofread by an external proofreader who audited the final version of the ESQ in English, Swedish and Latvian.

    Pilot testing

    The translated versions in Swedish, English, Latvian were ready for linguistic validation through pilot testing. The pilot tests of the translated versions were conducted in each country [13]. The questionnaire was completed by 10 participants in each country consisting of nurses and physiotherapists for face validation of the ESQ. Only minor changes were made after the piloting, such as changing terminologies to incorporate both physiotherapists and nurses within the specific healthcare environments.

    Psychometric evaluation

    Statistical analysis

    Items distributions are presented as frequency and percentage. Skewness and kurtosis statistics were computed to assess the distributional characteristics of the items. Values outside the range of −2 to + 2 for skewness and − 7 to + 7 for kurtosis were considered as potential deviations from normality [14].

    The internal consistency of the ESQ was measured using Cronbach’s α and McDonald’s ω, with values higher than 0.7 indicating acceptable internal consistency. The item-total correlation (corrected for overlap) was further computed to measure the internal consistency with values higher than 0.4 indicating satisfactory consistency [15, 16].

    The factor structure of the 9 items of the ESQ was assessed using exploratory factor analysis (EFA) with maximum likelihood extraction and varimax rotation. Sampling adequacy and the suitability of the correlation matrix were assessed using the Kaiser-Meyer-Olkin (KMO) test and Bartlett’s test of sphericity, respectively. A value higher than 0.6, along with a significant Bartlett’s test of sphericity, indicates the factorability of the data [17]. Significant factor loadings with a magnitude of > 0.40 were considered meaningful. The Scree plot and Kaiser rule were used to determine the number of factors to retain.

    To investigate whether the items of the ESQ correspond with their underlying concept, a Rasch analysis using a partial credit model (PCM) was conducted [14]. Item fit was measured using indices including Outfit and infit mean square (MnSq) with values between 0.5 and 1.5 indicating good fit [18]. Local independence between the items was assessed by computing residual correlations between any two items of ESQ, with values higher than 0.2 indicating a violation of local independence. Differential item functioning (DIF) was computed to measure the measurement invariance of the ESQ items across gender and profession subgroups. A DIF contrast of 0.64 was set as a cut-off for a meaningful statistically significant DIF [19].

    Finally, to evaluate the relationship between the ESQ items and general ethical safety, a network analysis was conducted. Network analysis is valuable for examining complex relationships and interactions between study variables and visualising these associations. In network analysis, each variable can be represented as a node, and the association between each node is referred to as an edge. The centrality of the nodes was determined by analyzing three metrics including degree centrality, betweenness centrality, and closeness centrality. The network analysis was computed using EBICglasso (Extended Bayesian Information Criterion Graphical Least Absolute Shrinkage Selection Operator) estimation, employing the non-parametric bootstrap procedure with 500 iterations to analyse the 95% confidence interval (CI) of edge weights [20]. All statistical analyses were performed using SPSS version 27, JASP version 0.18.3.0 and Winsteps version 4.3.0.

    Ethical considerations

    The study follows the guidelines on research from the Declaration of Helsinki, regarding research on human subjects [18]. The respective University Ethics Committees approved the present study, including the Research Ethics Committee of Turku University of Applied Sciences (1/2023), Riga Stradins University Research Ethics Committee (2-PEK-4/507/2023) and the University of Malta, Faculty of Health Sciences Research Ethics Committee (FHS-2023-00077), and ethical guidelines according Swedish law (SFS: 2003:460) was followed, and accordingly approval to conduct the study was gained by the head of the clinics of the involved hospital. Additional permissions were addressed depending on specific country’s requirements. Furthermore, permissions were obtained from the executive directors of the respective study sites and the directors of the departments or head nurses. Informed consent was obtained from individual participants through completion of the questionnaire and participation was voluntary and anonymous; participants could withdraw their participation if they do not submit the survey.

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  • Exclusive: Charging Trump foes over mortgage misstatements would be rare step, data shows – Reuters

    1. Exclusive: Charging Trump foes over mortgage misstatements would be rare step, data shows  Reuters
    2. Exclusive | DOJ Opens Criminal Investigation Into Fed’s Cook, Issues Subpoenas  The Wall Street Journal
    3. Exclusive-Charging Trump Foes Over Mortgage Misstatements Would Be Rare Step, Data Shows  U.S. News & World Report
    4. The ‘bizarre’ referral of the US housing finance agency chief to oust Lisa Cook  inkl
    5. The US Justice Department supports Trump’s right to fire Federal Reserve Governor Lisa Cook.  วารสารการเงินธนาคาร

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  • Mesenchymal Stem Cell Approach Meets End Points in Placebo-Controlled Trial of Parkinson Disease

    Mesenchymal Stem Cell Approach Meets End Points in Placebo-Controlled Trial of Parkinson Disease

    A recently published phase 2 randomized, placebo-controlled trial demonstrated that three infusions of 10 × 10⁶ allogeneic human mesenchymal stem cells (allo-hMSCs) significantly improved motor function in patients with mild to moderate Parkinson disease (PD). Additional clinical trials are needed to ensure consistency and reliability of allo-hMSC batches, as investigators observed a profound improvement in the placebo group and a less robust improvement in the two-infusion group.1

    Conducted between November 2020 and July 2023, the study comprised 45 patients with PD who received either 3 allo-hMSC infusions (n = 16), 1 placebo followed by 2 allo-hMSC infusions (n = 14), or 3 placebo infusions at 18-week intervals (n = 15). Over an 88-week follow-up, the primary outcome assessed was achieving at least a 70% posterior probability (PP) of a difference in the proportion of patients with a ≥5-point improvement in OFF-medication MDS-UPDRS Part III scores at week 62.

    Led by Mya C. Schiess, MD, a neurologist at UTHealth Houston Neurosciences Neurology, Texas Medical Center, a greater proportion of patents in the 3-infusion group achieved at least a 5-point improvement in MDS-UPDRS III compared with placebo at week 62 (mean difference, 5.0%; 95% credible Bayesian interval, –2.3% to 24.8%; PP = 93.7%). Using a more stringent threshold of at least 11 points, the results remained consistent, with more patient in the 3-infusion group improving relative to placebo (MD, 13.3%; 95% Crl, –6.1% to 37.8%; PP = 91.5%).

    At week 62, fewer patients in the 2-infusion group met the primary end point (MD, –62.4%; 95% Crl, –85.5% to –32.1%; PP ≥99.9%) as well as the more stringent threshold (MD, –63.8%; 95% Crl, –86.0% to –32.5%; PP≥99.9%). Additional data from this time point revealed a –16.9-point (–19.5% to –14.2%) improvement in the 3-infusion group, –3.9-point (95% Crl, –6.9% to –1.1%) improvement in the 2-infusion group, and a –14.6-point (95% Crl, –17.5% to –11.6%) improvement in the placebo group. Overall, the three-infusion group differed from placebo by −2.3 points (95% CrI, −6.1 to 1.6; PP = 87.8%), while the two-infusion group showed a +20.6-point difference (95% CrI, −37.6 to 24.5; PP ≥99.9%).

    READ MORE: Fully Enrolled CYPRESS Phase 3 Trial to Test Ampreloxetine in Symptomatic Neurogenic Orthostatic Hypotension of MSA

    Regarding the high improvement in placebo scores, the study authors wrote, “Although this finding may seem counterintuitive, it is important to note that studies on PD progression suggest an average annual motor decline (increase) of approximately 2.4 points in MDS-UPDRS-III scores. Yet in this trial, all treatment groups showed improvement in their motor scores over the 88 weeks of participation; an outcome that may, in part, reflect a placebo effect.”

    They went on to add that the residual placebo effect may have influenced the results since the primary outcome was assessed at week 62, which was 26 weeks or approximately 6 months after the last infusion. By week 88, and with a more stringent threshold (≥11-point improvement in MDS-UPDRS-III), the differences between the 3-infusion and placebo groups widened (–3.3 points; 95% Crlm –7.3% to 0.7%; PP = 94.7%), supportive of a waning placebo response. For context, the 2-infusion group remained worse than placebo by +9.0 points (95% Crl, 4.8% to 13.0%; PP ≥99.9%) by week 88.

    When compared with placebo, more participants in the 3-infusion group achieved at least a 12-point improvement in MDS-UPDRS at week 62 (MD, 22.0%; 95% Crl, –21.0% to 49.4%; PP = 96.3%) and week 88 (MD, 48.4; 95% Crl, 23.9% to 74.0%; PP ≥99.9%). In line with other data, fewer participants in the 2-infusion group showed improvement relative to placebo at week 62 (MD, –43.0; 95% Crl, –71.2% to –8.3%; PP = 99.1%) and at week 88 (MD, –20.8; 95% Crl, –53.1% to 14.1%; PP = 87.8%).

    In terms of safety, 10 mild and transient treatment-emergent adverse events were reported, with no severe events. In the 3-infusion group, single cases of malaise, transient hypertension not requiring medication, and vomiting occurred, while the two-infusion group experienced only constitutional symptoms (fatigue, flu-like symptoms, headache), all of which resolved. Three patients initially showed a panel reactive antibody response presumed to be donor-specific, but HLA typing confirmed two were unrelated to the donor, and the third—found in a placebo patient—was also deemed unrelated after unblinding.

    REFERENCE
    1. Schiess MC, Suescun J, Martinez-Lemus JD, et al. Allogeneic Bone Marrow-Derived Mesenchymal Stem Cells for Parkinson’s Disease: A Randomized Trial. Mov Disord. Published online September 1, 2025. doi:10.1002/mds.70028

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  • The Strad – Resetting your violin technique: lessons from the 1714 Stradivari, ‘Kneisel’

    The Strad – Resetting your violin technique: lessons from the 1714 Stradivari, ‘Kneisel’

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    When I recently received a loan of a 1714 Antonio Stradivari violin from Carriage House Violins in Boston, I discovered something unexpected: getting used to a new instrument isn’t just about adaptation — it’s an opportunity for a complete technical reset.

    This particular violin, from Stradivari’s golden period, carries remarkable history. It belonged to Franz Kneisel, founder of America’s first professional string quartet, and premiered Dvořák’s ‘American’ Quartet, along with works by Debussy, Ravel, and Schoenberg’s Verklärte Nacht.

    But beyond its illustrious past, this instrument became my teacher, forcing me to recalibrate every aspect of my technique. Whether you’re adjusting to a new violin or seeking to refine your current playing, the exercises and ideas in this video can transform your approach as well.

    The three dimensions of intonation

    In my view, every note exists in three dimensions: how it sounds, how it feels, and how it looks. When adapting to a new instrument, let’s recalibrate these elements:

    Sound goes beyond simple pitch accuracy. Each violin has unique resonance patterns — certain notes excite sympathetic vibrations, air modes and body modes differently. I practise slow scales, listening not just for pitch but for how each note activates these acoustical phenomena. When the violin suddenly ’lights up’ at certain frequencies, you’ve found its sweet spots. This Stradivari, with its slightly different string length compared to my personal violin, required me to rediscover where each note truly resonates.

    Feel involves developing a physical map of your fingerboard. In fourth position, does your hand touch the instrument’s rib? Where does your palm contact the bout in high positions? These tactile landmarks become your GPS system. On the Strad, my usual reference points shifted slightly — what was a perfect fourth-position F on my violin was now slightly sharp. These millimetre differences matter.

    Visual checkpoints might seem unconventional, but they work. Looking with my right eye, I can see where my finger intersects with certain visual markers to find specific pitches. It’s one more tool in the accuracy arsenal.

    Shifting without a safety net

    Most violinists rely heavily on ‘preparation notes’ — that quick moment where we touch the destination note before vibrating it. But practising ’air shifts’ removes this crutch entirely. You lift your finger, shift in the air, and land directly on the target pitch. It’s terrifying and transformative.

    My favourite shifting exercise is single-finger arpeggios, moving through all positions, strings and fingers. The pattern I use to do this is quite simple, and doesn’t take long. The exercise also doubles as expressive training – treating each shift as a musical portamento rather than a mechanical motion.

    Sound production reset

    We know that sound production operates mainly on three interdependent variables: contact point (where the bow meets string), bow speed, and pressure. Many players get stuck treating these as separate parameters to adjust independently. Instead, I use an exercise called ’waves’ to integrate various parameters into a ‘feeling’ that one can manipulate. 

    Using consistent bow speed, you create rhythmic indentations with your index finger, naturally adjusting weight and contact point in a pattern. The bow moves closer to the bridge with increased pressure, then retreats — like waves! This organic approach reveals the instrument’s pressure limits and optimal sound points without intellectualising the process.

    This Stradivari surprised me — it accepts tremendous pressure without cracking, yet also produces that legendary golden, ethereal sound with the lightest touch. Each instrument has its own personality in this regard.

    Chord playing as diagnostic tool

    In the video below, I use Bach’s Sarabande from the Cello Suites (sorry, cellists) as a perfect vehicle for recalibrating chord playing and coordination. Every instrument has a unique threshold for how aggressively you can ’carve through’ multiple strings. Some require a gentle roll; others, like this Strad, allow you to drive through with remarkable depth as long as you maintain momentum.

    I also discuss the importance of careful finger placement – especially for 5ths! Even high-level players naturally default to more pressure to ’push’ the 5th into tune. This is counter-productive and not reliable!

    The broader reset

    What struck me most about this experience wasn’t just learning a new instrument — it was how the process revitalised my fundamental technique. When everything feels slightly different, you can’t rely on muscle memory alone. You must return to conscious, deliberate practice.

    This recalibration opportunity doesn’t require a Stradivari. Any change — a new bow, different strings, even returning to playing after a break — can serve as a catalyst for technical renovation. The key is recognising these moments not as obstacles but as invitations to rediscover and refine your craft.

    For violinists at any level, the message is clear: embrace change, and keep things fresh. 

    Listen to the 1714 ‘Kneisel’ Stradivari violin live in concert in the video below:

     

     

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