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New treatment could reduce brain damage from stroke, study in mice shows

Cambridge scientists have developed and tested a new drug in mice that has the potential to reduce damage to the brain when blood flow is restored following a stroke.

The study, “Local arterial administration of acidified malonate as an adjunct therapy to mechanical thrombectomy in ischemic stroke” was published in Cardiovascular Research.

As many as one in four people will have a stroke during their lifetime. This is when a blood clot prevents oxygen from reaching a part of the brain. The first few hours following a stroke are crucial—the blood clot needs to be removed quickly so that the to the brain can be restored; otherwise, the brain tissue begins to die.

Reduced levels of miRNAs 449 and 34 in sperm of mice and men exposed to early life stress

Many studies have confirmed that exposure to severe stress during childhood has long-lasting negative health effects. One of the most convincing has been the Adverse Childhood Experience (ACE) Study, which is supported by over 100 publications1. It was initiated by collaboration between the Centers for Disease Control and Prevention and Kaiser Permanente’s Department of Preventive Medicine. It led to the ACE Study Questionnaire (see http://www.acestudy.org/index.html), where anonymous yes or no answers to 10 questions involving participant’s experiences at home until the age of 18 are quantified. Five are personal questions about physical abuse, verbal abuse, sexual abuse, physical neglect, and emotional neglect. Five relate to other family members: an alcoholic parent, a victim of domestic violence, incarceration, diagnosed with a mental illness, and the disappearance of a parent through divorce, death, or abandonment. A score ≥4 puts one at serious risk for future mental and physical health problems, such as a 4.6-fold increased rate of depression2 and a ~30-fold increased rate of suicidal ideation and attempts in adults3. Remarkably, 10% of the population reports scores of ≥4.

There is a growing appreciation that clinicians should be aware of patients’ traumatic experiences, particularly when young, because they add to their risk for physical and psychiatric maladies4,5. Moreover, sensitivity to PTSD has been shown to correlate with ACE score6,7,8 implying it can be used as a screening tool to identify people who should take extra precaution to avoid trauma. However, some may not answer the ACE questionnaire accurately due to suppressed memories or because of the sensitive nature of many of the questions, particularly in settings that do not allow anonymity. Thus, discovery of unbiased markers for early trauma could complement ACE surveys in some clinical settings.

Moreover, offspring of those exposed to early life trauma are at elevated risk for psychiatric disorders9. This phenomena has also been demonstrated in rodents10,11. For example, transmission of the effects of stress across generations has been observed after exposing male mice to a wide variety of psychological stresses, including social defeat12, chronic physical restraint13, multiple variable perturbations in adults14, social instability beginning in adolescence15, and early maternal separation16. While some evidence in mice points to environmentally induced changes in sperm DNA methylation as a mechanism for transmission of stress phenotypes16, the best evidence to date supports small RNA species in sperm. Recent studies show that sperm contain various types of cytoplasmic RNAs (e.g., mRNAs, miRNAs, siRNAs, lnc-RNAs, piwi-interacting RNAs, and fragments of tRNAs) that have the potential to contribute to embryo development17,18,19.

PIK3CA inhibitor treatment for metastatic scrotal extramammary Paget’s disease: a case report and literature review

Background: Extramammary Paget’s disease (EMPD) is a rare intraepithelial adenocarcinoma that occurs in the genitals, axilla, and anus, where apocrine sweat glands are abundant. This disease is mainly characterized by localized lesions and rare distant metastasis. Scrotal Paget’s disease is a rare type of EMPD, and there is no standard treatment for metastatic EMPD.

Case Description: Here, we reported the genetic results of a patient with a PIK3CA gene mutation in scrotal Paget’s disease who developed multiple metastases to the lymph nodes, liver, and bones during adjuvant radiotherapy, as well as the results of treatment with a PIK3CA inhibitor. The latest advances in this field were also summarized. The treatment response was evaluated as stable disease (SD) after 6 courses of docetaxel plus tegafur (DS regimen) chemotherapy. Then, a second-line treatment, a PIK3CA inhibitor, WX390, was administered with tolerable toxicity. There was a treatment-induced increase in blood glucose level during treatment, and insulin was administrated with good control. The progression-free survival (PFS) was 3.9 months and the overall survival (OS) was 16 months.

Conclusions: PIK3CA is a commonly mutated gene in EMPD. To the best of our knowledge, this is the first case report of a PIK3CA inhibitor for the treatment of primary metastatic EMPD, and the treatment efficacy was good. PIK3CA inhibitors may be promising for the treatment of metastatic EMPD in the future.

Synthetic data boosts gait analysis: AI trained on simulations rivals existing models

Gait assessment is critical for diagnosing and monitoring neurological disorders, yet current clinical standards remain largely subjective and qualitative. Recent advances in AI have enabled more quantitative and accessible gait analysis using widely available sensors such as smartphone cameras.

However, most existing AI models are designed for specific patient populations and sensor configurations, primarily due to the scarcity of diverse clinical datasets—a constraint often driven by privacy concerns. As a result, these models tend to underperform when applied to populations or settings not well represented in the , limiting their broader clinical applicability.

In a study published in Nature Communications, researchers from IBM Research, the Cleveland Clinic, and the University of Tsukuba propose a novel framework to overcome this limitation. Their approach involves generating synthetic gait data using generative AI trained on physics-based musculoskeletal simulations.

Stopping DNA damage in T cells during PARP inhibitor cancer treatment enhances antitumor effectiveness

The cancer drugs called PARP inhibitors have a puzzling reputation: even though they are treatment mainstays for multiple forms of cancer, they can damage cancer-killing T cells and disrupt the potential for meaningful therapy. New research from medical scientists in China is revealing ways to sidestep this obstacle by preventing PARP-induced collateral damage to T cells.

A multi-disciplinary team of researchers in Wuhan, working at several collaborating institutions, developed methods to prevent damage and showed that doing so increases the drugs’ efficacy against ovarian tumors and may help expand PARP inhibitors’ overall use. The PARP inhibitor drug family consists of slightly more than half a dozen medications, and the same problems appear consistent in all of them, say investigators participating in the study at Tongji Hospital, Tongji Medical College and Huazhong University of Science and Technology.

Writing in the journal Science Translational Medicine, the Wuhan-based researchers explain that PARP inhibitors have become standard treatments for , the most lethal gynecologic cancer. However, PARP inhibitors often can’t eliminate tumors on their own. Doctors have attempted to combine PARP medication with immunotherapies, such as , but results have been mixed, creating yet another obstacle in the PARP treatment saga.

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