Massachusetts General Hospital and the Shanghai Mental Health Center:the past,present and future of a psychiatric research partnership

INTRODUCTION There are many obstacles to developing,maintaining and strengthening international research collaborations,whether they are posed by geography,culture or,most recently,global economics and politics.It is critically important to overcome these obstacles,especially when it comes to fostering the types of breakthrough biomedical science that benefit from diverse perspectives,methodologies and data sets.Moreover,the research underlying these breakthroughs unfolds over the course of years,and even decades.For these reasons,and more,the Department of Psychiatry at Massachusetts General Hospital(Mass General)and the Shanghai Mental Health Center(SMHC)are taking the long view:exploring and implementing numerous collaborative research and training projects that are leading to better care and treatments for patients,both in the USA and China,who suffer from a range of psychiatric disorders.

Therapeutic potential of exercise-hormone irisin in Alzheimer's disease

Irisin is a myokine that is generated by cleavage of the membrane protein fibronectin type Ⅲ domain-containing protein 5(FNDC5) in response to physical exercise. Studies reveal that irisin/FNDC5 has neuroprotective functions against Alzheimer's disease, the most common form of dementia in the elderly, by improving cognitive function and reducing amyloid-β and tau pathologies as well as neuroinflammation in cell culture or animal models of Alzheimer's disease. Although current and ongoing studies on irisin/FNDC5 show promising results, further mechanistic studies are required to clarify its potential as a meaningful therapeutic target for alleviating Alzheimer's disease. We recently found that irisin treatment reduces amyloid-β pathology by increasing the activity/levels of amyloid-β-degrading enzyme neprilysin secreted from astrocytes. Herein, we present an overview of irisin/FNDC5's protective roles and mechanisms against Alzheimer's disease.

Exploring the novel role of oligodendrocyte precursor cells in phagocytosis:beyond myelinogenesis

Roles of oligodendrocyte precursor cells in the central nervous system:Oligodendrocyte precursor cells(OPCs)have long been recognized for their critical role as precursors to oligodendrocytes,the primary myelin-producing cells.As precursors,OPCs mature and differentiate into oligodendrocytes,which contribute significantly to the formation of myelin sheaths around axons.This myelination,which is critical for the conduction of salutatory nerve impulses in the cerebral white matter,underscores the classical role of oligodendrocytes in central nervous system(CNS)functionality.Importantly,because oligodendrocytes are differentiated cells that cannot proliferate.

Iron-handling solute carrier SLC22A17 as a blood-brain barrier target after stroke

The pathophysiology of ischemic stroke is complex and multifactorial,involving various forms of cell death such as apoptosis,autophagy,and necrosis.A recent study suggests that oxidative and inflammatory stress can induce ferroptosis,a specialized form of cell death characterized by the accumulation of lipid peroxides dependent on intracellular iron overload(Li and Jia,2023).

Sleep as a window to understand and regulate Alzheimer's disease:emerging roles of thalamic reticular nucleus

Introduction:Alzheimer 's disease(AD) is a common neurodegenerative disorder and the primary cause of dementia. Considerable evidence supports the “amyloid hypothesis,” stating that the pathogenesis of AD is primarily caused by the deposition of amyloid-β(Aβ), which drives tau phosphorylation, neuroinflammation, and neurodegeneration in the brain. The amyloid hypothesis is strengthened by the significant and moderate benefit of lecanemab, a humanized antibody through an anti-amyloid mechanism,showing slowed clinical decline(van Dyck et al.,2023). The recent positive results of anti-amyloid trials have brought back focus on the amyloid hypothesis through biochemical, genetic, and pharmacological approaches(Zhang, 2023).

Hospital readmissions in decompensated cirrhotics: Factors pointing toward a prevention strategy

AIM To reduce readmissions and improve patient outcomes in cirrhotic patients through better understanding of readmission predictors.METHODS We performed a single-center retrospective study of patients admitted with decompensated cirrhosis from January 1, 2011 to December 31, 2013(n = 222). Primary outcomes were time to first readmission and 30-d readmission rate due to complications of cirrhosis. Clinical and demographic data were collected to help describe predictors of readmission, along with care coordination measures such as post-discharge status and outpatient follow-up. Univariate and multivariateanalyses were performed to describe variables associated with readmission.RESULTS One hundred thirty-two patients(59.4%) were readmitted at least once during the study period. Median time to first and second readmissions were 54 and 93 d, respectively. Thirty and 90-d readmission rates were 20.7 and 30.1 percent, respectively. Predictors of 30-d readmission included education level, hepatic encephalopathy at index, ALT more than upper normal limit and Medicare coverage. There were no statistically significant differences in readmission rates when stratified by discharge disposition, outpatient follow-up provider or time to first outpatient visit.CONCLUSION Readmissions are challenging aspect of care for cirrhotic patients and risk continues beyond 30 d. More initiatives are needed to develop enhanced, longitudinal post-discharge systems.

Hospital Acquired Infections in Low and Middle Income Countries: Root Cause Analysis and the Development of Infection Control Practices in Bangladesh

Nosocomial or hospital acquired infections are a major challenge for low and middle income countries (LMICs) which have limited healthcare resources. Risk factors include the lack of appropriate hospital facilities such as isolation units, bed space, and sinks;inadequate waste management, contaminated equipment, inappropriate use of antibiotics and transmission of infection from the hands of healthcare workers and family caretakers due to inadequate hand washing. Nosocomial infections increase the costs of healthcare due to added antimicrobial treatment and prolonged hospitalization. Since the prevalence of nosocomial infections is generally higher in developing countries with limited resources, the socio-economic burden is even more severe in these countries. This review summarizes the current knowledge on the risks of hospital acquired infections and summarizes current recommendations for the development of hospital infrastructure and the institution of protocols to reduce these infections in LMICs such as Bangladesh.

Risk Factors for Wound Infection Following Caesarean Section: A Case Control Study from Sir Salimullah Medical College &Mitford Hospital in Dhaka, Bangladesh

Background: Post caesarean section (CS) wound infection or surgical site infection is a leading cause of prolonged hospital stay or readmission. An understanding of its risk factors is important. Methods: A case control study was conducted in the Department of Obstetrics and Gynecology of Sir Salimullah Medical College & Mitford Hospital, in Dhaka, Bangladesh from January to June 2014 to evaluate the risk factors of postoperative surgical site infection following CS. One hundred patients were studied. Results: Fifty patients of post CS wound infection (surgical site infection: SSI) were selected as cases. Body mass index > 25 (kg/m2), anemia (p = 0.001), prolonged rupture of membrane (p = 0.005), prolonged operation time (p = 0.019), and junior surgeons performing the operation (p = 0.011) were the risk factors for CS-SSI. Conclusions: Pre- and postoperative care and surgical training of junior doctors should be directed to these risk factors.

Hospital Admission Less than 30 Days after Chemotherapy: Results from a Chemotherapy-Specific Morbidity and Mortality Conference in Gynecologic Oncology

Introduction: Morbidity and Mortality (M&M) rounds can identify adverse events and improve patient safety however adoption in cancer centers is not routine. Herein we report the results of a chemotherapy-specific gynecologic oncology M&M rounds and identify reasons for hospital admission < 30 days after chemotherapy treatment. Methods: Between July 2014 and April 2016, all admissions < 30 days from chemotherapy administration were prospectively collected along with clinical data. Admissions were described and classified as planned or unplanned and as associated with chemotherapy or with underlying disease. Results: 585 patients were admitted, 78% of whom had ovarian cancer and 43% of whom had recurrent disease. Overall, 47% of admissions were unplanned and these were significantly longer than planned admissions (5.6 vs. 2.4 days, p = 0.0003). Of unplanned admissions, 43% were due to chemotherapy, and 57% were due to disease burden. 74% of patients had received >1 prior line of chemotherapy, and 22% were on clinical trial. The most common causes of unplanned admission were nausea, vomiting or failure to thrive (28.9%), fever (17.9%) and small bowel obstruction (19.9%). Conclusions: There is a high rate of unplanned admission < 30 days after chemotherapy and patients with ovarian cancer and recurrent disease are at the highest risk. This information can be used to counsel patients about complications of chemotherapy and to improve supportive management. M&M conferences surrounding unplanned admissions after chemotherapy may help guide therapy, encourage best supportive care, and prompt re-evaluation of treatment goals in heavily pretreated patients with recurrent.

Neoadjuvant Chemotherapy Followed by Surgery versus Primary Surgery in Advanced Epithelial Ovarian Cancer: A Review of Outcomes at National Institute of Cancer Research Hospital in Bangladesh

Introduction: This study evaluated the difference in operative and clinical outcomes for patients with advanced ovarian cancer after primary debulking surgery (PDS) versus neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) in Bangladesh. Methods: Sixty patients with advanced epithelial ovarian cancer presenting to the department of Gynaecological Oncology at the National Institute of Cancer Research and Hospital were prospectively enrolled. Thirty patients underwent primary debulking surgery and thirty patients received NACT followed by IDS. Results: In the PDS and IDS groups respectively, 56.7% and 50% of patients presented with stage IIIC and 67.7% and 56.7% respectively had serious papillary type histopathology. Duration of surgery, amount of blood loss and total hospital stay were significantly lower (p < 0.001) in IDS group than in the PDS group. There was a statistically significant difference in postoperative tumor residuals between IDS and PDS patients. Complete tumor resection (R0) was obtained in 24 (80%) of IDS patients versus 13 (43.3%) PDS patients. In fifteen months of follow-up, 21 (70%) in the PDS group and 5 (16.7%) in the IDS group recurred (p = 0.021). Median progression free survival in PDS patients was twelve months while that of the IDS group was seventeen months. There was one death at 45 days in the PDS group. No other deaths were documented at fifteen months of follow-up. Conclusion: Interval debulking surgery has a more favorable outcome than primary debulking surgery on progression free survival in advanced ovarian cancer patients and permits a less aggressive surgery to be performed in Bangladesh.

Anatomical Modeling of Brain Vasculature in Two-Photon Microscopy by Generalizable Deep Learning

Objective and Impact Statement.Segmentation of blood vessels from two-photon microscopy(2PM)angiograms of brains has important applications in hemodynamic analysis and disease diagnosis.Here,we develop a generalizable deep learning technique for accurate 2PM vascular segmentation of sizable regions in mouse brains acquired from multiple 2PM setups.The technique is computationally efficient,thus ideal for large-scale neurovascular analysis.Introduction.Vascular segmentation from 2PM angiograms is an important first step in hemodynamic modeling of brain vasculature.Existing segmentation methods based on deep learning either lack the ability to generalize to data from different imaging systems or are computationally infeasible for large-scale angiograms.In this work,we overcome both these limitations by a method that is generalizable to various imaging systems and is able to segment large-scale angiograms.Methods.We employ a computationally efficient deep learning framework with a loss function that incorporates a balanced binary-cross-entropy loss and total variation regularization on the network’s output.Its effectiveness is demonstrated on experimentally acquired in vivo angiograms from mouse brains of dimensions up to 808×808×702μm.Results.To demonstrate the superior generalizability of our framework,we train on data from only one 2PM microscope and demonstrate high-quality segmentation on data from a different microscope without any network tuning.Overall,our method demonstrates 10×faster computation in terms of voxels-segmented-per-second and 3×larger depth compared to the state-of-the-art.Conclusion.Our work provides a generalizable and computationally efficient anatomical modeling framework for brain vasculature,which consists of deep learning-based vascular segmentation followed by graphing.It paves the way for future modeling and analysis of hemodynamic response at much greater scales that were inaccessible before.

Individual and Environmental Risk Factors for COVID-19 Mortality in Elderly in 7 European University Hospitals

Because the elderly account for 80% of deaths from COVID-19 and they may be more vulnerable to air pollution, in this retrospective study we aimed to explore individual and environmental risk factors for COVID-19 mortality in the geriatric departments of seven European University hospitals, between February and May 2020. Long-term exposure to air pollution was estimated through annual pollutant concentrations at the residential address over the last two years. Short-term variations in air pollutants and weather parameters were also examined through a 20-day period before the confirmed PCR diagnostic of COVID-19. We found positive associations for diabetes and COVID-19 mortality (OR 2.2 CI 95%: 1.1, 4.4). Regarding environmental factors, we found no association between COVID-19 mortality and air pollutants and weather parameters;however, our study suffers from strong disparities—such as patient characteristics—between fairly polluted and less polluted cities. In order to overcome those disparities between cities, we aimed to explore the relationship between air pollution and COVID-19 mortality within each city, but even with the high-efficiency modelisation systems, differences in air pollutants were too small to estimate the effect of air pollution at the city level. Thus, this study highlights the need to improve the estimation of individual exposure to air pollution. To address this issue, solutions exist such as the increase of the number of fixed air monitors, or even better, through the use of individual markers of air pollution exposure such as urinary black carbon or passive individual samplers. Furthermore, we underline that outdoor air pollutant concentrations may not be representative of individual exposure, especially in the elderly, thus, we suggest that further studies focus on indoor air pollution. Regarding meteorological conditions, we found no association between UV, temperature, wind speed and COVID-19 mortality. We found a positive association between an increase in relative humidity (RH) and COVID-19 mortality, however, the influence of RH on COVID-19 mortality remains unclear, and additional studies are needed to confirm this potential link.

Prediction of treatment response to antipsychotic drugs for precision medicine approach to schizophrenia:randomized trials and multiomics analysis

Background:Choosing the appropriate antipsychotic drug(APD)treatment for patients with schizophrenia(SCZ)can be challenging,as the treatment response to APD is highly variable and difficult to predict due to the lack of effective biomarkers.Previous studies have indicated the association between treatment response and genetic and epigenetic factors,but no effective biomarkers have been identified.Hence,further research is imperative to enhance precision medicine in SCZ treatment.Methods:Participants with SCZ were recruited from two randomized trials.The discovery cohort was recruited from the CAPOC trial(n=2307)involved 6 weeks of treatment and equally randomized the participants to the Olanzapine,Risperidone,Quetiapine,Aripiprazole,Ziprasidone,and Haloperidol/Perphenazine(subsequently equally assigned to one or the other)groups.The external validation cohort was recruited from the CAPEC trial(n=1379),which involved 8 weeks of treatment and equally randomized the participants to the Olanzapine,Risperidone,and Aripiprazole groups.Additionally,healthy controls(n=275)from the local community were utilized as a genetic/epigenetic reference.The genetic and epigenetic(DNA methylation)risks of SCZ were assessed using the polygenic risk score(PRS)and polymethylation score,respectively.The study also examined the genetic-epigenetic interactions with treatment response through differential methylation analysis,methylation quantitative trait loci,colocalization,and promoteranchored chromatin interaction.Machine learning was used to develop a prediction model for treatment response,which was evaluated for accuracy and clinical benefit using the area under curve(AUC)for classification,R^(2) for regression,and decision curve analysis.Results:Six risk genes for SCZ(LINC01795,DDHD2,SBNO1,KCNG2,SEMA7A,and RUFY1)involved in cortical morphology were identified as having a genetic-epigenetic interaction associated with treatment response.The developed and externally validated prediction model,which incorporated clinical information,PRS,genetic risk score(GRS),and proxy methylation level(proxyDNAm),demonstrated positive benefits for a wide range of patients receiving different APDs,regardless of sex[discovery cohort:AUC=0.874(95%CI 0.867-0.881),R^(2)=0.478;external validation cohort:AUC=0.851(95%CI 0.841-0.861),R^(2)=0.507].Conclusions:This study presents a promising precision medicine approach to evaluate treatment response,which has the potential to aid clinicians in making informed decisions about APD treatment for patients with SCZ.Trial registration Chinese Clinical Trial Registry(https://www.chictr.org.cn/),18 Aug 2009 retrospectively registered:CAPOC-ChiCTR-RNC-09000521(https://www.chictr.org.cn/showproj.aspx?proj=9014),CAPEC-ChiCTRRNC-09000522(https://www.chictr.org.cn/showproj.aspx?proj=9013).

The efficacy of vitamin E in preventing arthrofibrosis after joint replacement

Background:Arthrofibrosis is a joint disorder characterized by excessive scar formation in the joint tissues.Vitamin E is an antioxidant with potential anti-fibroblastic effect.The aim of this study was to establish an arthrofibrosis rat model after joint replacement and assess the effects of vitamin E supplementation on joint fibrosis.Methods:We simulated knee replacement in 16 male Sprague–Dawley rats.We immobilized the surgical leg with a suture in full flexion.The control groups were killed at 2 and 12 weeks(n=5 per group),and the test group was supplemented daily with vitamin E(0.2 mg/mL)in their drinking water for 12 weeks(n=6).We performed histological staining to investigate the presence and severity of arthrofibrosis.Immunofluorescent staining andα2-macroglobulin(α2M)enzyme-linked immunosorbent assay(ELISA)were used to assess local and systemic inflammation.Static weight bearing(total internal reflection)and range of motion(ROM)were collected for functional assessment.Results:The ROM and weight-bearing symmetry decreased after the procedure and recovered slowly with still significant deficit at the end of the study for both groups.Histological analysis confirmed fibrosis in both lateral and posterior periarticular tissue.Vitamin E supplementation showed a moderate anti-inflammatory effect on the local and systemic levels.The vitamin E group exhibited significant improvement in ROM and weight-bearing symmetry at day 84 compared to the control group.Conclusions:This model is viable for simulating arthrofibrosis after joint replacement.Vitamin E may benefit postsurgical arthrofibrosis,and further studies are needed for dosing requirements.

Intergenerational Trauma and Resilience among Im/Migrant Families: Child Mental Health Outcomes and Psychosocial Mechanisms of Transmission

Research Background: Psychological stressors leading to poor mental health outcomes accumulate throughout the migration process. The impact of a parent or caregiver’s posttraumatic stress on non-traumatized children is significant and may lead to adverse development and mental health outcomes. Research Objectives: The objective of this review is to explore both the consequences of parental trauma transmission on descendants’ psychological adjustment and well-being, and the mechanisms through which trauma has been transmitted among im/migrant populations. Methods: Criteria outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement guided this systemic review. The questions guiding this review are: (a) What are the consequences of parental trauma transmission on the psychological adjustment and well-being of im/migrant offspring? And (b) What are the psychosocial mechanisms of trauma and resilience transmission among im/migrant populations? Each potential study was assessed based on relevance to the review question(s). Results: Parental trauma can lead to adverse mental health outcomes among descendants including increased internalizing and externalizing problems, the adoption of coping behaviors and worldviews, and worsening school performance. Mechanisms that influence trauma transmission include parental trauma symptom severity, the parent-child dyad, social learning, and family stressors. Pathways of resilience exist across socioecological levels to include individual resilience such as coping skills and meaning making, family resilience, structural protective factors, and social and cultural protective factors. Conclusions: Despite the prevalence of traumatic events throughout the migration process, im/migrant families display strong levels of resilience. Mental health services and providers should incorporate a strength-based approach in designing interventions that are culturally responsive and take into accounts the broader ecological contexts in which im/migrant families live.

An environmentally sensitive zinc-selective two-photon NIR fluorescent turn-on probe and zinc sensing in stroke

A two-photon near infrared(NIR)fluorescence turn-on sensor with high selectivity and sensitivity for Zn^(2+)detection has been developed.This sensor exhibits a large Stokes'shift(-300 nm)and can be excited from 900 to 1000 nm,with an emission wavelength of-785 nm,making it ideal for imaging in biological tissues.The sensor's high selectivity for Zn^(2+)over other structurally similar cations,such as Cd^(2+),makes it a promising tool for monitoring zinc ion levels in biological systems.Given the high concentration of zinc in thrombi,this sensor could provide a useful tool for in vivo thrombus imaging.

Mistreatment during Childbirth: Impact on Maternal Outcomes and Importance of Provider Perspectives

Background: Dying in childbirth is one of the most common causes of death for women. While maternal mortality rates, defined as deaths per 100,000 live births, have been steadily dropping in most countries worldwide, maternal mortality rates have doubled in the United States in the last twenty years. This commentary examines the various contributing factors to this trend. Methods: A literature review was performed using the keywords: maternal mortality, United States, disrespectful maternity care, obstetric violence, provider perspectives, and disparities. Maternal mortality statistics were obtained from the World Health Organization website. Results: Medical factors associated with maternal mortality include increased maternal age and cardiovascular conditions. Social factors include barriers to healthcare access, delays in receiving medical care, reduction in reproductive health services in some states, and non-obstetrical deaths such as accidents, domestic violence, and suicide. Racial inequities and disparities of care are reflected in higher maternal mortality rates for minorities and people of color. Disrespectful maternity care or obstetric violence has been reported worldwide as a factor in delay of lifesaving obstetrical care and reluctance by a pregnant person to access the healthcare system. About one in five US women has reported experiencing mistreatment, varying from verbal abuse to lack of privacy, from coerced procedures to neglect during childbirth. Conclusion: This commentary highlights the importance of inclusion of providers in research on respectful maternity care. Provider burnout, moral distress, limited time, and burden of clinical responsibilities are known challenges to respectful and comprehensive medical care. The association of disrespectful care with poor maternal outcomes needs to be studied. Exploring root causes of disrespectful childbirth care can empower nurses, midwives, and physicians to improve their environment and find solutions to reduce a potential cause of maternal mortality.

Ten misconceptions regarding decision-making in critical care

Diagnostic errors are prevalent in critical care practice and are associated with patient harm and costs for providers and the healthcare system.Patient complexity,illness severity,and the urgency in initiating proper treatment all contribute to decision-making errors.Clinician-related factors such as fatigue,cognitive overload,and inexperience further interfere with effective decision-making.Cognitive science has provided insight into the clinical decision-making process that can be used to reduce error.This evidence-based review discusses ten common misconceptions regarding critical care decision-making.By understanding how practitioners make clinical decisions and examining how errors occur,strategies may be developed and implemented to decrease errors in Decision-making and improve patient outcomes.

Maternal Mortality Rates among Im/Migrant Populations in the United States

Introduction: Maternal mortality rates have more than doubled in the U.S over the last two decades, making it one of the few places in the world where maternal mortality is increasing. Differences in maternal mortality among certain races and ethnicities are known but few studies examine maternal mortality among immigrants. Since immigrants represent 13.7% of the U.S. population, it is essential to examine immigrant subsets to understand maternal mortality among this vulnerable population. Methods: A literature search identified 318 articles on maternal mortality and immigrants, with 12 articles from the U.S. The keywords included maternal mortality, United States, migrants, asylum seekers, immigrants, and disparities. Maternal mortality statistics were obtained from the World Health Organization and Center for Disease Control. Results: Studies analyzed in this review found an overall lower maternal mortality rate among immigrant women compared to U.S.-born women, except for Hispanic immigrant women. Black women had the highest maternal mortality rate, regardless of immigration status. Conclusion: Although the literature points to lower maternal mortality among immigrants, the data is still somewhat mixed, making it challenging to draw comprehensive conclusions. Additional research examining maternal mortality among Im/migrants in the U.S. is needed to guide future training among healthcare professionals and policymakers.

Whole-eye transplantation: Current challenges and future perspectives

Whole-eye transplantation emerges as a frontier in ophthalmology,promising a transformative approach to irreversible blindness.Despite advancements,formidable challenges persist.Preservation of donor eye viability post-enucleation necessitates meticulous surgical techniques to optimize retinal integrity and ganglion cell survival.Overcoming the inhibitory milieu of the central nervous system for successful optic nerve regeneration remains elusive,prompting the exploration of neurotrophic support and immunomodulatory interventions.Immunological tolerance,paramount for graft acceptance,confronts the distinc-tive immunogenicity of ocular tissues,driving research into targeted immunosup-pression strategies.Ethical and legal considerations underscore the necessity for stringent standards and ethical frameworks.Interdisciplinary collaboration and ongoing research endeavors are imperative to navigate these complexities.Biomaterials,stem cell therapies,and precision immunomodulation represent promising avenues in this pursuit.Ultimately,the aim of this review is to critically assess the current landscape of whole-eye transplantation,elucidating the challenges and advancements while delineating future directions for research and clinical practice.Through concerted efforts,whole-eye transplantation stands to revolu-tionize ophthalmic care,offering hope for restored vision and enhanced quality of life for those afflicted with blindness.