The 2022 symposium on dementia and brain aging in low- and middle-income countries: Highlights on research, diagnosis, care, and impact.

Two of every three persons living with dementia reside in low- and middle-income countries (LMICs). The projected increase in global dementia rates is expected to affect LMICs disproportionately. However, the majority of global dementia care costs occur in high-income countries (HICs), with dementia research predominantly focusing on HICs. This imbalance necessitates LMIC-focused research to ensure that characterization of dementia accurately reflects the involvement and specificities of diverse populations. Development of effective preventive, diagnostic, and therapeutic approaches for dementia in LMICs requires targeted, personalized, and harmonized efforts. Our article represents timely discussions at the 2022 Symposium on Dementia and Brain Aging in LMICs that identified the foremost opportunities to advance dementia research, differential diagnosis, use of neuropsychometric tools, awareness, and treatment options. We highlight key topics discussed at the meeting and provide future recommendations to foster a more equitable landscape for dementia prevention, diagnosis, care, policy, and management in LMICs. HIGHLIGHTS: Two-thirds of persons with dementia live in LMICs, yet research and costs are skewed toward HICs. LMICs expect dementia prevalence to more than double, accompanied by socioeconomic disparities. The 2022 Symposium on Dementia in LMICs addressed advances in research, diagnosis, prevention, and policy. The Nairobi Declaration urges global action to enhance dementia outcomes in LMICs.

Walking the tightrope: Fertility preservation among hereditary breast and ovarian Cancer syndrome Previvors.

INTRODUCTION: Fertility-related concerns cause significant anxiety among patients with Hereditary Breast and Ovarian Cancer Syndrome (HBOC). The Society of Gynecologic Oncology and the American Society for Reproductive Medicine recommend patients diagnosed with HBOC receive early referral to a reproductive endocrinologist. However, evidence about fertility trends in this patient population are limited and guidelines are scarce. The aim of this study is to compare fertility preservation among patients with HBOC to control patients undergoing fertility treatment without a diagnosis of infertility. METHODS: This retrospective study included patients who presented to a single academic institution for fertility preservation in the setting of diagnosis of HBOC. In this study, HBOC patients are referred to as those who had tested positive for pathogenic mutations in BRCA1, BRCA2 or were at high-risk for HBOC based on a strong family history (defined as >3 family members diagnosed with HBOC) without a genetic mutation. HBOC patients were matched in a 1:1 fashion to a control group undergoing fertility preservation without a diagnosis of infertility or HBOC. All analysis was done using SPSS version 9.4 (SAS Institute, Cary, NC). RESULTS: Between August 1st, 2016 and August 1st, 2022, 81 patients presented to the study center for consultation in the setting of HBOC. Of those who presented, 48 (59.2%) ultimately underwent oocyte cryopreservation and 33 (40.7%) underwent embryo cryopreservation. Patients who underwent oocyte cryopreservation due to BRCA1 status were more likely to present for fertility consultation at a younger age compared to control patients (32.6 vs. 34.7 years, p = 0.03) and were more likely to undergo oocyte cryopreservation at a younger age (32.1 vs. 34.6 years, p = 0.007). There was no difference in age at initial consultation or age at procedure for patients with BRCA2 or patients with a strong family history compared to control patients (p > 0.05). There was no difference in the mean age of patients with HBOC at presentation for consultation for embryo cryopreservation or the mean age the patient with HBOC underwent embryo cryopreservation compared to control patients (p > 0.05). Patients with BRCA1 or BRCA2 did not have expedited time from consultation to first cycle start (p > 0.05). After adjusting for factors including anti-Müllerian hormone (AMH) level and age, patients considered in the HBOC group due to family history had less time between consultation and oocyte cryopreservation cycle compared to control patients. (179 vs. 317 days, p = 0.045). There was no difference in time from consultation to starting cycle for embryo cryopreservation for patients with HBOC compared to controls (p > 0.05). CONCLUSION: Patients with HBOC did not undergo expedited fertility treatment compared to control patients undergoing oocyte and embryo cryopreservation for non-infertility reasons. Patients diagnosed with BRCA1 had more oocytes retrieved compared to the control population which is possibly due to earlier age of presentation in the setting of recommended age of risk reducing surgery being age 35-40. When age matched, cycle outcomes did not differ between HBOC and control patients. Given the known cancer prevention benefit and recommendations for risk-reducing surgery, future studies should focus on guidelines for fertility preservation for patients with HBOC.

Neutralization sensitivity of SARS-CoV-2 Omicron variants FL.1 and GE.1 by therapeutic antibodies and XBB sera.

Two SARS-CoV-2 XBB sub-variants, FL.1 and GE.1, have been increasing in prevalence worldwide, but limited information is available about their ability to evade the immune system. FL.1 and GE.1 are emerging Omicron XBB variants possessing additional mutations in the spike RBD raising concerns of increased neutralization escape. In this study, we assessed the neutralizing ability of eleven FDA-approved monoclonal antibody combinations against different Omicron variants, including BA.2.75, BA.2.76, BA.4/5, XBB.1.5, and CH.1.1. Among the eleven antibodies, Sotrovimab was the only antibody to show broad neutralization ability against XBB.1.5. However, Sotrovimab showed attenuated neutralization efficiency against recently emerging XBB sub-lineages EG.5, FL.1, and GE.1 compared to XBB.1.5. Additionally, XBB.1.5 seropositive convalescent sera displayed lower neutralization activity against EG.5, FL.1, and GE.1. Overall, our findings present enhanced immune evasion capacity of emerging XBB variants and emphasize the importance of continued monitoring of novel variants.

Community health worker outreach to farmworkers in rural North Carolina: Learning from adaptations to the SARS-CoV-2 pandemic.

BACKGROUND: Community health workers represent a critical part of the health outreach and services for migrant and seasonal farmworkers ('farmworkers') in rural areas of the United States. PURPOSE: We sought to identify adaptations to farmworker patient engagement and health outreach made by community health workers during the first 18 months of the COVID-19 pandemic. METHODS: In this qualitative study, we used semi-structured interviews with community health workers from August 2020 to February 2022 (n = 21). Two coders used thematic analysis to identify three themes related to the experiences of community health workers in conducting health education and outreach to farmworkers prior to and following the onset of the pandemic. FINDINGS: We found themes related to pre-pandemic outreach efforts to provide health education resource sharing with farmworkers and pandemic-related outreach efforts that included adoption of porch drops and distanced delivery of health education, adaptation of modes of health education and communication through technology and the internet, and taking on new roles related to COVID-19. Finally, we identified changes that reverted after the pandemic or will continue as adaptations. CONCLUSIONS: Community health workers created practice-based innovations in outreach in response to the COVID-19 pandemic. These innovations included new COVID-19 related roles and new modes of health education and outreach, including the use of digital resources. The changes developed for emergency use in COVID-19, particularly related to internet and technology, have likely altered how community health workers conduct outreach in North Carolina going forward. Funders, community health worker training programs, and researchers should take note of these innovations. PATIENT OR PUBLIC CONTRIBUTION: Community health workers who typically come from patient populations and provide critical navigation and connection with the health care system advised on the design and creation of this research project, including serving on an advisory board. Two authors have experience working as community health workers.

Effect of postthaw change in embryo score on single euploid embryo transfer success rates.

OBJECTIVE: To assess whether the change in embryo morphology from precryopreservation to postthaw is associated with the embryo transfer success rates in single euploid embryo transfer cycles. DESIGN: Retrospective cohort study. SETTING: Academic affiliated fertility clinic. PATIENT(S): Patients who underwent a single euploid embryo transfer cycle from September 2016 to April 2022 were included. A decision support tool was used to assign each embryo a reproductive potential score on the basis of the day of biopsy, expansion, and grade of trophectoderm and inner cell mass at the time of cryopreservation and after thaw. Embryos were divided into 4 groups: group 1 included embryos with the same score after thaw (reference); group 2 included those with a higher score; group 3 included those with a lower score; and group 4 included those that did not re-expand after thaw. INTERVENTION(S): No interventions administered. MAIN OUTCOME MEASURE(S): The primary outcome was the live birth rates (LBRs) per embryo transfer. The secondary outcomes included the chemical pregnancy, clinical pregnancy, and clinical pregnancy loss rates. Comparative statistics and univariate analyses were performed using the Kruskal-Wallis and χ2tests. Multivariate logistic regression fitted with generalized estimating equation was performed to compare the odds of live birth between groups. RESULT(S): A total of 7,750 embryo transfers performed for 4,613 patients met inclusion criteria: 5,331 in group 1; 486 in group 2; 1,726 in group 3; and 207 in group 4. In the univariate analysis, there was a statistically significant difference in the LBR between groups 1, 2, 3, and 4 (55.8% vs. 51.4%, 47.5%, and 26.6%). Logistic regression controlling for oocyte age, antimüllerian hormone, body mass index, endometrial thickness, year of embryo transfer, time from thaw to final grading, and embryo score before cryopreservation showed significantly lower odds of live birth when the embryo was downgraded (odds ratio [OR], 0.70; confidence interval [CI], 0.62-0.79) or did not re-expand (OR, 0.36; CI, 0.26-0.51) than those with no change in score. When controlling for all variables, there was a significant increase in the odds of live birth between embryos that had a higher score after thaw and those without a change (OR, 1.42; CI, 1.14-1.76). There was no significant difference in the clinical pregnancy loss rate among the 4 groups. CONCLUSION(S): The change in the quality of the embryo after thaw is an important factor in embryo transfer success. In an adjusted analysis, the chemical and clinical pregnancy rates and LBR per embryo transfer all significantly decrease in embryos that were downgraded or did not expand on the day of single euploid embryo transfer. Embryos that re-expand and have improved quality after thaw have the highest odds of live birth.

Cognitive and functional performance and plasma biomarkers of early Alzheimer's disease in Down syndrome.

INTRODUCTION: People with Down syndrome (DS) have a 75% to 90% lifetime risk of Alzheimer's disease (AD). AD pathology begins a decade or more prior to onset of clinical AD dementia in people with DS. It is not clear if plasma biomarkers of AD pathology are correlated with early cognitive and functional impairments in DS, and if these biomarkers could be used to track the early stages of AD in DS or to inform inclusion criteria for clinical AD treatment trials. METHODS: This large cross-sectional cohort study investigated the associations between plasma biomarkers of amyloid beta (Aß)42/40, total tau, and neurofilament light chain (NfL) and cognitive (episodic memory, visual-motor integration, and visuospatial abilities) and functional (adaptive behavior) impairments in 260 adults with DS without dementia (aged 25-81 years). RESULTS: In general linear models lower plasma Aß42/40 was related to lower visuospatial ability, higher total tau was related to lower episodic memory, and higher NfL was related to lower visuospatial ability and lower episodic memory. DISCUSSION: Plasma biomarkers may have utility in tracking AD pathology associated with early stages of cognitive decline in adults with DS, although associations were modest. Highlights: Plasma Alzheimer's disease (AD) biomarkers correlate with cognition prior to dementia in Down syndrome.Lower plasma amyloid beta 42/40 was related to lower visuospatial abilities.Higher plasma total tau and neurofilament light chain were associated with lower cognitive performance.Plasma biomarkers show potential for tracking early stages of AD symptomology.

Comparison of tau spread in people with Down syndrome versus autosomal-dominant Alzheimer's disease: a cross-sectional study.

BACKGROUND: In people with genetic forms of Alzheimer's disease, such as in Down syndrome and autosomal-dominant Alzheimer's disease, pathological changes specific to Alzheimer's disease (ie, accumulation of amyloid and tau) occur in the brain at a young age, when comorbidities related to ageing are not present. Studies including these cohorts could, therefore, improve our understanding of the early pathogenesis of Alzheimer's disease and be useful when designing preventive interventions targeted at disease pathology or when planning clinical trials. We compared the magnitude, spatial extent, and temporal ordering of tau spread in people with Down syndrome and autosomal-dominant Alzheimer's disease. METHODS: In this cross-sectional observational study, we included participants (aged ≥25 years) from two cohort studies. First, we collected data from the Dominantly Inherited Alzheimer's Network studies (DIAN-OBS and DIAN-TU), which include carriers of autosomal-dominant Alzheimer's disease genetic mutations and non-carrier familial controls recruited in Australia, Europe, and the USA between 2008 and 2022. Second, we collected data from the Alzheimer Biomarkers Consortium-Down Syndrome study, which includes people with Down syndrome and sibling controls recruited from the UK and USA between 2015 and 2021. Controls from the two studies were combined into a single group of familial controls. All participants had completed structural MRI and tau PET (18F-flortaucipir) imaging. We applied Gaussian mixture modelling to identify regions of high tau PET burden and regions with the earliest changes in tau binding for each cohort separately. We estimated regional tau PET burden as a function of cortical amyloid burden for both cohorts. Finally, we compared the temporal pattern of tau PET burden relative to that of amyloid. FINDINGS: We included 137 people with Down syndrome (mean age 38·5 years [SD 8·2], 74 [54%] male, and 63 [46%] female), 49 individuals with autosomal-dominant Alzheimer's disease (mean age 43·9 years [11·2], 22 [45%] male, and 27 [55%] female), and 85 familial controls, pooled from across both studies (mean age 41·5 years [12·1], 28 [33%] male, and 57 [67%] female), who satisfied the PET quality-control procedure for tau-PET imaging processing. 134 (98%) people with Down syndrome, 44 (90%) with autosomal-dominant Alzheimer's disease, and 77 (91%) controls also completed an amyloid PET scan within 3 years of tau PET imaging. Spatially, tau PET burden was observed most frequently in subcortical and medial temporal regions in people with Down syndrome, and within the medial temporal lobe in people with autosomal-dominant Alzheimer's disease. Across the brain, people with Down syndrome had greater concentrations of tau for a given level of amyloid compared with people with autosomal-dominant Alzheimer's disease. Temporally, increases in tau were more strongly associated with increases in amyloid for people with Down syndrome compared with autosomal-dominant Alzheimer's disease. INTERPRETATION: Although the general progression of amyloid followed by tau is similar for people Down syndrome and people with autosomal-dominant Alzheimer's disease, we found subtle differences in the spatial distribution, timing, and magnitude of the tau burden between these two cohorts. These differences might have important implications; differences in the temporal pattern of tau accumulation might influence the timing of drug administration in clinical trials, whereas differences in the spatial pattern and magnitude of tau burden might affect disease progression. FUNDING: None.

Transcriptome profiling and analysis of patients with esophageal squamous cell carcinoma from Kazakhstan.

Esophageal squamous cell carcinoma (ESCC) is the predominant subtype of esophageal cancer in Central Asia, often diagnosed at advanced stages. Understanding population-specific patterns of ESCC is crucial for tailored treatments. This study aimed to unravel ESCC's genetic basis in Kazakhstani patients and identify potential biomarkers for early diagnosis and targeted therapies. ESCC patients from Kazakhstan were studied. We analyzed histological subtypes and conducted in-depth transcriptome sequencing. Differential gene expression analysis was performed, and significantly dysregulated pathways were identified using KEGG pathway analysis (p-value < 0.05). Protein-protein interaction networks were constructed to elucidate key modules and their functions. Among Kazakhstani patients, ESCC with moderate dysplasia was the most prevalent subtype. We identified 42 significantly upregulated and two significantly downregulated KEGG pathways, highlighting molecular mechanisms driving ESCC pathogenesis. Immune-related pathways, such as viral protein interaction with cytokines, rheumatoid arthritis, and oxidative phosphorylation, were elevated, suggesting immune system involvement. Conversely, downregulated pathways were associated with extracellular matrix degradation, crucial in cancer invasion and metastasis. Protein-protein interaction network analysis revealed four distinct modules with specific functions, implicating pathways in esophageal cancer development. High-throughput transcriptome sequencing elucidated critical molecular pathways underlying esophageal carcinogenesis in Kazakhstani patients. Insights into dysregulated pathways offer potential for early diagnosis and precision treatment strategies for ESCC. Understanding population-specific patterns is essential for personalized approaches to ESCC management.

Lgr5+ intestinal stem cells are required for organoid survival after genotoxic injury.

Progenitors and mature cells can maintain the intestinal epithelium by dedifferentiation and facultative intestinal stem cell (fISC) function when active ISCs (aISCs) are lost to damage. Here, we sought to model fISC activation in intestinal organoids with doxorubicin (DXR), a chemotherapeutic known to ablate Lgr5+ aISCs in vivo. We identified low and high doses of DXR compatible with long-term organoid survival. Similar fISC gene activation was observed between organoids treated with low vs high DXR, despite significantly decreased survival at the higher dose. aISCs exhibit dose-dependent loss after DXR but survive at doses compatible with organoid survival. We ablated residual aISCs after DXR using a Lgr52A-DTR allele and observed that aISC survival of the initial genotoxic insult is required for organoid survival following DXR. These results suggest that while typical fISC genes are activated by DXR injury in organoids, functional stemness remains dependent on the aISC pool. Our data establish a reproducible model of DXR injury in intestinal organoids and reveal differences in in vitro responses to an established in vivo damage modality.

Synergistic controls of water column stability and groundwater phosphate on coastal algal blooms.

Algal blooms have been identified as one major threat to coastal safety and marine ecosystem functioning, but the dominant mechanism regulating the formation of algal blooms remains controversial, ranging from physical control (via water column stability), the chemical control (via coastal nutrients) to joint control. Here we leveraged the unique data collected in the Hong Kong water over the annual cycle and past three decades, including direct observations of algal blooms and coastal nutrients and process model output of water column stability, and evaluated the differential competing hypotheses in regulating algal blooms. Our results demonstrate that the joint mechanism rather than the single mechanism effectively predicts all algal blooms. Meanwhile, we observed that the adequate nutrients (phosphate, PO43-) significantly originate from coastal groundwater. The production and fluctuation of PO43- in beach aquifers are primarily governed by groundwater temperature, leading to a sustained and sufficient supply of PO43- in a low groundwater temperature environment. Furthermore, along with submarine groundwater discharge (SGD), the ongoing release of PO43- in groundwater enters coastal waters and serves as sufficient nourishment for promoting algal blooms in coastal areas. These results highlight the importance of both physical and chemical mechanisms, as well as SGD, in regulating coastal algal blooms. These findings have practical implications for the prevention of coastal algal blooms and provide insights into mariculture, water security, and the sustainability of coastal ecosystems.

Prodromal Alzheimer's disease can affect activities of daily living for adults with Down syndrome.

INTRODUCTION: Alzheimer's disease (AD) affecting adults with Down syndrome (DS-AD), like late-onset AD (LOAD) in the neurotypical population, has preclinical, prodromal, and more advanced stages. Only tasks placing high demands on cognition are expected to be affected during the prodromal stage, with activities of daily living (ADLs) typically being spared. However, cognitive demands of ADLs could be high for adults with DS and may be affected during prodromal DS-AD. METHODS: Cognitively stable cases that subsequently developed prodromal DS-AD were identified within a set of archived data from a previous longitudinal study. Measures of ADLs and multiple cognitive domains were examined over time. RESULTS: Clear declines in ADLs accompanied cognitive declines with prodromal DS-AD while stability in all measures was verified during preclinical DS-AD. DISCUSSION: Operationally defining prodromal DS-AD is essential to disease staging in this high-risk population and for informing treatment options and timing as new disease-modifying drugs become available. Highlights: Cognitive and functional stability were demonstrated prior to the onset of prodromal DS-AD.ADL declines accompanied cognitive declines as adults with DS transitioned to prodromal AD.Declines in ADLs should be a defining feature of prodromal AD for adults with DS.Better characterization of prodromal DS-AD can improve AD diagnosis and disease staging.Improvements in DS-AD diagnosis and staging could also inform the timing of interventions.

Lessons for the next pandemic: analysis of the timing and outcomes including post-discharge decannulation rates for tracheostomy in severe COVID-19 respiratory failure.

PURPOSE: COVID-19 patients with respiratory failure frequently require prolonged ventilatory support that would typically warrant early tracheostomy. There has been significant debate on timing, outcomes, and safety of these procedures. The purpose of this study was to determine the epidemiological, hospital, and post-discharge outcomes of this cohort, based on early (ET) versus late (LT) tracheostomy. METHODS: Retrospective review (March 2020-January 2021) in a 5-hospital system of ventilated patients who underwent tracheostomy. Demographics, hospital/ICU length of stay (LOS), procedural characteristics, APACHE II scores at ICU admission, stabilization markers, and discharge outcomes were analyzed. Long-term decannulation rates were obtained from long-term acute care facility (LTAC) data. RESULTS: A total of 97 patients underwent tracheostomy (mean 61 years, 62% male, 64% Hispanic). Despite ET being frequently performed during active COVID infection (85% vs. 64%), there were no differences in complication types or rates versus LT. APACHE II scores at ICU admission were comparable for both groups; however, > 50% of LT patients met PEEP stability at tracheostomy. ET was associated with significantly shorter ICU and hospital LOS, ventilator days, and higher decannulation rates. Of the cohort discharged to an LTAC, 59% were ultimately decannulated, 36% were discharged home, and 41% were discharged to a skilled nursing facility. CONCLUSIONS: We report the first comprehensive analysis of ET and LT that includes LTAC outcomes and stabilization markers in relation to the tracheostomy. ET was associated with improved clinical outcomes and a short LOS, specifically on days of pre-tracheostomy ventilation and in-hospital decannulation rates.

Dexamphetamine increased speech and visual unimodal illusions in healthy participants without affecting temporal binding window.

OBJECTIVE: Stimuli received beyond a very short timeframe, known as temporal binding windows (TBWs), are perceived as separate events. In previous audio-visual multisensory integration (McGurk effect) studies, widening of TBWs has been observed in people with schizophrenia. The present study aimed to determine if dexamphetamine could increase TBWs in unimodal auditory and unimodal visual illusions that may have some validity as experimental models for auditory and visual hallucinations in psychotic disorders. METHODS: A double-blind, placebo-controlled, counter-balanced crossover design with permuted block randomisation for drug order was followed. Dexamphetamine (0.45 mg/kg, PO, q.d.) was administered to healthy participants. Phantom word illusion (speech illusion) and visual-induced flash illusion/VIFI (visual illusion) tests were measured to determine if TBWs were altered as a function of delay between stimuli presentations. Word emotional content for phantom word illusions was also analysed. RESULTS: Dexamphetamine significantly increased the total number of phantom words/speech illusions (p < 0.01) for pooled 220-1100 ms ISIs in kernel density estimation and the number of positive valence words heard (beta = 2.20, 95% CI [1.86, 2.55], t = 12.46, p < 0.001) with a large effect size (std. beta = 1.05, 95% CI [0.89, 1.22]) relative to placebo without affecting the TBWs. For the VIFI test, kernel density estimation for pooled 0-801 ms ISIs showed a significant difference (p < 0.01) in the data distributions of number of target flash (es) perceived by participants after receiving dexamphetamine as compared with placebo. CONCLUSIONS: Overall, healthy participants who were administered dexamphetamine (0.45 mg/kg, PO, q.d.) experienced increases in auditory and visual illusions in both phantom word illusion and VIFI tests without affecting their TBWs.

BANKSY unifies cell typing and tissue domain segmentation for scalable spatial omics data analysis.

Spatial omics data are clustered to define both cell types and tissue domains. We present Building Aggregates with a Neighborhood Kernel and Spatial Yardstick (BANKSY), an algorithm that unifies these two spatial clustering problems by embedding cells in a product space of their own and the local neighborhood transcriptome, representing cell state and microenvironment, respectively. BANKSY's spatial feature augmentation strategy improved performance on both tasks when tested on diverse RNA (imaging, sequencing) and protein (imaging) datasets. BANKSY revealed unexpected niche-dependent cell states in the mouse brain and outperformed competing methods on domain segmentation and cell typing benchmarks. BANKSY can also be used for quality control of spatial transcriptomics data and for spatially aware batch effect correction. Importantly, it is substantially faster and more scalable than existing methods, enabling the processing of millions of cell datasets. In summary, BANKSY provides an accurate, biologically motivated, scalable and versatile framework for analyzing spatially resolved omics data.

To the point: Utility of laparoscopy for operative management of stabbing abdominal trauma.

BACKGROUND: Algorithms for managing penetrating abdominal trauma are conflicting or vague regarding the role of laparoscopy. We hypothesized that laparoscopy is underutilized among hemodynamically stable patients with abdominal stab wounds. METHODS: Trauma Quality Improvement Program data (2016-2019) were used to identify stable (SBP ≥110 and GCS ≥13) patients ≥16yrs with stab wounds and an abdominal procedure within 24hr of admission. Patients with a non-abdominal AIS ≥3 or missing outcome information were excluded. Patients were analyzed based on index procedure approach: open, therapeutic laparoscopy (LAP), or LAP-conversion to open (LCO). Center, clinical characteristics and outcomes were compared according to surgical approach and abdominal AIS using non-parametric analysis. RESULTS: 5984 patients met inclusion criteria with 7 â€‹% and 8 â€‹% receiving therapeutic LAP and LCO, respectively. The conversion rate for patients initially treated with LAP was 54 â€‹%. Compared to conversion or open, therapeutic LAP patients had better outcomes including shorter ICU and hospital stays and less infection complications, but were younger and less injured. Assessing by abdominal AIS eliminated ISS differences, meanwhile LAP patients still had shorter hospital stays. At time of admission, 45 â€‹% of open patients met criteria for initial LAP opportunity as indicated by comparable clinical presentation as therapeutic laparoscopy patients. CONCLUSIONS: In hemodynamically stable patients, laparoscopy remains infrequently utilized despite its increasing inclusion in current guidelines. Additional opportunity exists for therapeutic laparoscopy in trauma, which appears to be a viable alternative to open surgery for select injuries from abdominal stab wounds. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level IV.

Whole genome-wide sequence analysis of long-lived families (Long-Life Family Study) identifies MTUS2 gene associated with late-onset Alzheimer's disease.

INTRODUCTION: Late-onset Alzheimer's disease (LOAD) has a strong genetic component. Participants in Long-Life Family Study (LLFS) exhibit delayed onset of dementia, offering a unique opportunity to investigate LOAD genetics. METHODS: We conducted a whole genome sequence analysis of 3475 LLFS members. Genetic associations were examined in six independent studies (N = 14,260) with a wide range of LOAD risk. Association analysis in a sub-sample of the LLFS cohort (N = 1739) evaluated the association of LOAD variants with beta amyloid (Aß) levels. RESULTS: We identified several single nucleotide polymorphisms (SNPs) in tight linkage disequilibrium within the MTUS2 gene associated with LOAD (rs73154407, p = 7.6 × 10-9). Association of MTUS2 variants with LOAD was observed in the five independent studies and was significantly stronger within high levels of Aß42/40 ratio compared to lower amyloid. DISCUSSION: MTUS2 encodes a microtubule associated protein implicated in the development and function of the nervous system, making it a plausible candidate to investigate LOAD biology. HIGHLIGHTS: Long-Life Family Study (LLFS) families may harbor late onset Alzheimer's dementia (LOAD) variants. LLFS whole genome sequence analysis identified MTUS2 gene variants associated with LOAD. The observed LLFS variants generalized to cohorts with wide range of LOAD risk. The association of MTUS2 with LOAD was stronger within high levels of beta amyloid. Our results provide evidence for MTUS2 gene as a novel LOAD candidate locus.

Medicare meets the cloud: the development of a secure platform for the storage and analysis of claims data.

Introduction: Cloud-based solutions are a modern-day necessity for data intense computing. This case report describes in detail the development and implementation of Amazon Web Services (AWS) at Emory-a secure, reliable, and scalable platform to store and analyze identifiable research data from the Centers for Medicare and Medicaid Services (CMS). Materials and Methods: Interdisciplinary teams from CMS, MBL Technologies, and Emory University collaborated to ensure compliance with CMS policy that consolidates laws, regulations, and other drivers of information security and privacy. Results: A dedicated team of individuals ensured successful transition from a physical storage server to a cloud-based environment. This included implementing access controls, vulnerability scanning, and audit logs that are reviewed regularly with a remediation plan. User adaptation required specific training to overcome the challenges of cloud computing. Conclusion: Challenges created opportunities for lessons learned through the creation of an end-product accepted by CMS and shared across disciplines university-wide.

Single Euploid Embryo Transfer Outcomes After Uterine Septum Resection.

STUDY OBJECTIVE: To study pregnancy outcomes after single euploid embryo transfer (SEET) in patients who underwent prior uterine septum resection to those with uteri of normal contour, without Müllerian anomalies or uterine abnormalities including polyps or fibroids, and without a history of prior uterine surgeries. DESIGN: Retrospective cohort study. SETTING: Single academic affiliated center. PATIENTS: 60 cycles of patients with prior hysteroscopic uterine septum resection who underwent an autologous SEET between 2012 and 2020 were used as the investigational cohort. A 3:1 ratio propensity score matched control cohort of 180 single euploid embryo transfer cycles from patients without a history of uterine septa were used as the control group. INTERVENTIONS: No interventions administered. MEASUREMENTS AND MAIN RESULTS: Pregnancy, clinical pregnancy loss, ongoing clinical pregnancy, and live birth rates in patients with a history of uterine septum resection compared with matched patients without Müllerian anomalies or uterine surgeries. Patients with a prior uterine septum had significantly lower rates of chemical pregnancy (58.33% vs 77.2%, p = .004), implantation (41.67% vs 65.6%, p = .001), and live birth (33.33% vs 57.8%, p = .001) per transfer. No statistical difference in clinical pregnancy loss rates was found when comparing septum patients with controls (8.33% vs 7.8%, p = .89). CONCLUSION: Patients with a history of hysteroscopic resection who undergo in vitro fertilization are more susceptible to suboptimal clinical outcomes compared with patients with normal uteri. Early pregnancy loss rates in patients with a uterine septum are higher than in those without; however, after resection, the rates are comparable. Patients born with septate uteri require assessment of surgical intervention prior to SEET, and to optimize their reproductive outcomes.

Family Building in Transgender Patients: Modern Strategies with Assisted Reproductive Technology Treatment.

Purpose: Transgender and gender diverse (TGD) individuals continue to face adversity, stigma, and inequality, especially in health care. This study aimed to characterize the experience of TGD people and partners of TGD people with regard to fertility treatment. Methods: All TGD patients presenting to a single academic center between 2013 and 2021 were included. Baseline demographics collected included patient age, body mass index, anti-Mullerian hormone, basal antral follicle count, history of gender-affirming surgery, and/or gender-affirming hormone therapy. Outcomes included total patients who progressed to treatment, cycle type(s), and clinical outcomes. Results: In total, 82 patients who identified as TGD or had a partner who identified as TGD presented to care seeking fertility treatment. Of the 141 planned cycles, 106 (75.2%) progressed to treatment. Of the 15 in vitro fertilization (IVF) and co-IVF cycles, 12 achieved live birth. Of the 76 intrauterine inseminations 7 patients were discharged with ongoing pregnancies and one achieved live birth. Conclusion: These findings reaffirm that TGD individuals utilize the entire array of fertility services. With recent advances in access to care and modern medicine, assisted reproductive technology treatment has the power to support TGD patients in building contemporary family structures.