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Laparoscopic retroperitoneal partial nephrectomy (LRPN) is a technically demanding kidney surgery due to the limited space and unfamiliar approach in the retroperitoneal space. The aim of this study is to review the outcome of our initial experience in performing this procedure. All patients who underwent LRPN between 2019 to 2022 were included in this retrospective review. A total of 23 patients underwent LRPN. The mean operating time was 178±43 minutes and mean warm ischemia time was 20±5 minutes. The average estimated blood lost was 89±68ml and the mean postoperative hospital stay was 3.6±0.8 days. Two patients (11.1%) had positive margin and no local recurrence was seen after mean follow up of 15.8±12.0 months. Our initial experience on LRPN showed promising results to perform partial nephrectomy safely and effectively.

Mixed-halide perovskites offer ideal bandgaps for tandem solar cells, but photoinduced halide segregation compromises photovoltaic device performance. This study explores the influence of a hole-transport layer, necessary for a full device, by monitoring halide segregation through in situ, concurrent X-ray diffraction and photoluminescence measurements to disentangle compositional and optoelectronic changes. This work demonstrates that top coating FA0.83Cs0.17Pb(Br0.4I0.6)3 perovskite films with a poly(triaryl)amine (PTAA) hole-extraction layer surprisingly leads to suppression of halide segregation because photogenerated charge carriers are rapidly trapped at interfacial defects that do not drive halide segregation. However, the generation of iodide-enriched regions near the perovskite/PTAA interface enhances hole back-transfer from the PTAA layer through improved energy level offsets, increasing radiative recombination losses. It is further found that while passivation with a piperidinium salt slows halide segregation in perovskite films, the addition of a PTAA top-coating accelerates such effects, elucidating the specific nature of trap types that are able to drive the halide segregation process. This work highlights the importance of selective passivation techniques for achieving efficient and stable wide-bandgap perovskite photovoltaic devices.

Reproductive-age women with bleeding disorders (BDs) are underdiagnosed and understudied, despite their increased risk for adverse health outcomes and pregnancy complications.This study examines pregnancy outcomes and obstetric complications of Utah women with BDs.This retrospective cohort study utilized linked birth records and clinical billing data from two large Utah healthcare systems. Utah residents who had their first birth at 20 weeks gestation (2008-2015) and who received non-emergent care within either system before delivery were included (n = 61 226). Multivariable logistic regression models were used to examine relationships between BDs and neonatal and obstetric outcomes.A total of 295 women (.48%) were included in the BD study population. Women with BDs had significantly increased odds of preterm birth (aOR 1.85, 95% CI 1.32-2.60), Caesarean delivery (aOR 1.38, 95% CI 1.06-1.79), postpartum blood transfusion (aOR 2.55, 95% CI 1.05-6.22), unplanned postpartum hysterectomy (aOR 33.96, 95% CI 7.30-157.89) and transfer to an intensive care unit (aOR 18.18, 95% CI 7.17-46.08). All of the women with BDs who experienced these serious complications were not diagnosed with a BD until the year of their first birth. Additionally, those with BDs were more likely to experience maternal and infant mortality.Women with BDs had an increased risk for preterm birth, Caesarean delivery, blood transfusion, unplanned hysterectomy, intensive care unit admission, maternal and infant mortality. Those who were not diagnosed with a BD before the year of their first birth were at an increased risk for serious pregnancy complications.

May-Thurner Syndrome (MTS) remains to be an overlooked condition wherein the right common iliac artery compresses the left common iliac vein. Rarely reported, MTS has other different variants with the iliac vein being compressed by an ipsilateral artery. Iliofemoral DVT poses a significant impact because of venous claudication and DVT recurrence. MTS usually occurs in women, ages 20–40 y/o, and is thus rarely included in differential diagnosis of DVT in elderly patients presenting with persistent unilateral leg swelling. Treatment of DVT alone with anticoagulation is insufficient to address thrombotic MTS. Failure to address the mechanical compression leads to poor quality of life due to high predisposition to recurrent DVT, and at times to other complications such as post-thrombotic syndrome and formation of AV fistulas. We present a case of an 89 year old woman, hypertensive, non-smoker, no history of cancer, presenting with progressive left lower extremity swelling with erythema, violaceous discoloration, varicosities, telangiectatic skin lesions, hyperpigmentation and calf tenderness. Ultrasound revealed DVT at common iliac vein extending to the popliteal veins. CT studies showed a left common iliac artery compressing the left common iliac vein with early enhancement of the common femoral vein, indicating presence of fistula. Peripheral angiography and venography findings were consistent with CT scan findings, with incidental findings of multiple small AV fistulas. Anti-coagulation was given and IVC filter was inserted. An attempt to do catheter-directed thrombolysis was unsuccessful. Subsequently, she underwent Palma's surgery which provided significant improvement and was sent home ambulatory.

Parental control for a child's handphone access is important to ensure online safety. This study was to determine parental control on handphone access and the usage amongst Malaysian children.A cross-sectional survey was conducted electronically between April 2017 and March 2018 among parents with children above 2 years of age, who owned a handphone. The 10-item questionnaire included questions about rules applied to the use of handphones, education on cybersafety, the characteristics and activities of their youngest children who had full-time access to a handphone, and parental perceptions of their children's usage of handphones. A total of 215 parents were included.From this, 92% controlled their children's handphones use by setting rules. The commonest rules were limiting the time of handphone usage (77%) and being aware of whom the child was communicating with (77%). The majority (94%) educated their children on cybersafety, and the commonest discussed topic was not to communicate with strangers (93%). The children's average age of first handphone ownership was 10.6 (SD: 3.6) years, and the use of the handphone averaged 17.4 (SD: 18.5) hours a week. Despite the rules and education provided, only a quarter of parents were confident of their children's capability to manage their own safety when using handphones (27%).In summary, Malaysian parents did control their children's handphone usage.

Milroy disease, known as primary congenital lymphedema, is characterized by chronic tissue swelling due to impaired lymphatic drainage and is inherited in an autosomal dominant manner. This study reports a rare case of Milroy disease affecting siblings from unaffected parents. A one-month-old female infant presented with swelling of the bilateral calf and the dorsum of the feet which had been present since birth. Her 14-month-old brother had a similar presentation since birth with swelling of the bilateral calf and the dorsum of the feet. Milroy disease was diagnosed based on the clinical findings of bilateral lower limb swelling and confirmed by molecular genetic testing. The patient and her family, including her brother, parents, and maternal grandfather, were genetically tested, and two novel missense mutations (NM_182925.4: c.2534TC; p.Leu845Pro, c.4006GA; p.Glu1336Lys) were found in the Fms-related tyrosine kinase (FLT4) gene. Mutations segregated by the parents who carried each mutation in the heterozygous state were identified in the patient and her brother. The present case report in which Milroy disease developed in all offspring of parents with a normal phenotype suggests the possibility of a compound heterozygous mutation or non-penetrance during the process of inheritance of Milroy disease.

In the past decades, water-related disasters had been accounted for about three-quarters of all-natural disasters worldwide. Asia is the most affected region with more than 45% of fatalities and more than 90% of the victims affected by aquatic disasters. Aquatic events progress differently and rapidly as compared to inland disasters. Thus, apart from additional equipments and trained aquatic rescuers, aquatic disaster operation requires specific strategies and tactics.This qualitative study was conducted using mixed methods involving the Delphi method and decision-conferencing approach. Two rounds of open-ended questionnaires were sent to subject matter experts from rescue agencies that involved in aquatic disaster rescue and management. Feedback from the panel was reviewed, the natural history of different aquatic disasters was appraised, and the decision-analysis model on the command, control and management of aquatic disaster was developed. The model was then reassessed through an iteration process at decision-conferencing among the expert panel until the final framework was accepted by all members of the panel.The fast progression of aquatic disasters with multiple hazards on the scene and unique technical challenges of the operation increase the risk of rescuers to become victims themselves. The developed conceptual framework, namely Aquatic Disaster Activation Plan and Tactic (ADAPT), was found able to guide rescuers in risk assessment, judgment, and response in aquatic disasters based on strategies and tactics for different phases along the natural history of aquatic disasters.With realistic scenario-based training and drills, ADAPT can be the blueprint in aquatic disaster management. It is designed to facilitate rescue agencies and organizations in preparing and executing the technical aquatic rescue operations safely, according to the resources available and the capability of the respective rescue organization.

Gain-of-function (GOF) mutations in CXCR4 cause WHIM (warts, hypogammaglobulinemia, infections, and myelokathexis) syndrome, characterized by infections, leukocyte retention in bone marrow (BM), and blood leukopenias. B lymphopenia is evident at early progenitor stages, yet why do CXCR4 GOF mutations that cause B (and T) lymphopenia remain obscure? Using a CXCR4 R334X GOF mouse model of WHIM syndrome, we showed that lymphopoiesis is reduced because of a dysregulated mesenchymal stem cell (MSC) transcriptome characterized by a switch from an adipogenic to an osteolineage-prone program with limited lymphopoietic activity. We identify lymphotoxin beta receptor (LTβR) as a critical pathway promoting interleukin-7 (IL-7) down-regulation in MSCs. Blocking LTβR or CXCR4 signaling restored IL-7 production and B cell development in WHIM mice. LTβR blocking also increased production of IL-7 and B cell activating factor (BAFF) in secondary lymphoid organs (SLOs), increasing B and T cell numbers in the periphery. These studies revealed that LTβR signaling in BM MSCs and SLO stromal cells limits the lymphocyte compartment size.

Pediatric steroid-sensitive nephrotic syndrome (pSSNS) is the most common childhood glomerular disease. Previous genome-wide association studies (GWAS) identified a risk locus in the HLA Class II region and three additional signals. But the genetic architecture of pSSNS, and its genetically driven pathobiology, is largely unknown. We conducted a multi-population GWAS meta-analysis in 38,463 participants (2,440 cases) and population specific GWAS, discovering twelve significant associations (eight novel). Fine-mapping implicated specific amino acid haplotypes in HLA-DQA1 and HLA-DQB1 driving the HLA Class II risk signal. Non-HLA loci colocalized with eQTLs of monocytes and numerous T-cell subsets in independent datasets. Colocalization with kidney eQTLs was lacking, but overlap with kidney cell open chromatin suggests an uncharacterized disease mechanism in kidney cells. A polygenic risk score (PRS) associated with earlier disease onset in two independent cohorts. Altogether, these discoveries expand our knowledge of pSSNS genetic architecture across populations and provide cellspecific insights into its molecular drivers.

After acute infection with Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), a significant proportion (0.2–30%) of patients experience persistent symptoms beyond 12 weeks, termed Long COVID. Understanding the mechanisms which cause this debilitating disease and identifying biomarkers for diagnostic, therapeutic and monitoring purposes is urgently required. Persistently high levels of IFN-γ were detected from peripheral blood mononuclear cells (PBMCs) of Long COVID patients using highly sensitive FluoroSpot assays. This IFN-γ release was seen in the absence of ex vivo peptide stimulation and remains persistently elevated in Long Covid patients, unlike the resolution seen in patients recovering from acute SARS-CoV-2 infection. IFN-γ release was CD8+ T cell mediated and dependent on MHC-I antigen presentation by CD14+ cells. After vaccination, a significant decrease in IFN-γ correlated with resolution of some Long COVID symptoms. Our study highlights a key mechanism underlying Long COVID, enabling the search for biomarkers and therapeutics in patients with Long COVID.

Asians are underrepresented across many omics databases, thereby limiting the potential of precision medicine in nearly 60% of the global population. As such, there is a pressing need for multi-omics derived quantitative trait loci (QTLs) to fill the knowledge gap of complex traits in populations of Asian ancestry. Here, we provide the first blood-based multi-omics analysis of Asian pregnant women, constituting high-resolution genotyping (N = 1079), DNA methylation (N = 915) and transcriptome profiling (N = 238). Integrative omics analysis identified 219 154 CpGs associated with cis-DNA methylation QTLs (meQTLs) and 3703 RNAs associated with cis-RNA expression QTLs (eQTLs). Ethnicity was the largest contributor of inter-individual variation across all omics datasets, with 2561 genes identified as hotspots of this variation; 395 of these hotspot genes also contained both ethnicity-specific eQTLs and meQTLs. Gene set enrichment analysis of these ethnicity QTL hotspots showed pathways involved in lipid metabolism, adaptive immune system and carbohydrate metabolism. Pathway validation by profiling the lipidome (~480 lipids) of antenatal plasma (N = 752) and placenta (N = 1042) in the same cohort showed significant lipid differences among Chinese, Malay and Indian women, validating ethnicity-QTL gene effects across different tissue types. To develop deeper insights into the complex traits and benefit future precision medicine research in Asian pregnant women, we developed iMOMdb, an open-access database.

The impact of sex and diabetes mellitus (DM) on patients with heart failure with mildly reduced ejection fraction (HFmrEF) is not well elucidated. This study aims to evaluate sex differences in the clinical profile and outcomes in Asian HFmrEF patients with and without DM.Patients admitted nationally for HFmrEF (ejection fraction 40-49%) between 2008 and 2014 were included and followed up until December 2016. The primary outcome was all-cause mortality. Secondary outcomes included cardiovascular (CV) death and/or heart failure (HF) rehospitalisations.A total of 2,272 HFmrEF patients (56% male) were included. More women had DM than men (60% versus 55%,Asian women with HFmrEF had a higher prevalence of DM, with differences in clinical characteristics, compared to men. While diabetes conferred poor outcomes regardless of sex, there were distinct sex differences. These highlight the need for sex-specific management strategies.

Herein, a grafted copolymer composed of carboxymethylcellulose (CMC) and polyethylene-glycol-aminated (PEG-NH2) was successfully synthesized via a facile ionic interaction and scalable route in the presence of EDC/NHS (N-ethyl-N′-(3-dimethylaminopropyl)carbodiimide/N-hydroxysuccinimide) activators. From Fourier transform infrared (FTIR) spectroscopy, the absorption peak at 1652 cm–1 corresponded to –NH groups of PEG-NH2. After grafting, the grafted CMC-PEG was characterized for surface morphology, crystallinity, functional groups determination, and thermal analysis. No cytotoxicity effect was observed in normal human dermal fibroblasts (NHDFs) cells following exposure to the grafted CMC-PEG up to 2 mg/ml. The rheological studies suggested that the optimized 10% (w/v) grafted CMC-PEG hydrogels crosslinked with 5% (w/v) citric acid (CA) exhibited better mechanical properties compared to the non-grafted CMC. This work highlights the characterizations of grafted CMC-PEG and demonstrates the potential of grafted CMC-PEG hydrogels crosslinked with CA for advanced 3D-bioprinting or as injectable hydrogels in various biomedical applications such as tissue engineering, wound dressing materials, and drug delivery systems.

Genetic and epidemiologic studies have significantly advanced our understanding of the genetic factors contributing to age-related macular degeneration (AMD). In particular, recent expression quantitative trait loci (eQTL) studies have highlighted POLDIP2 as a significant gene that confers risk of developing AMD. However, the role of POLDIP2 in retinal cells such as retinal pigment epithelium (RPE) and how it contributes to AMD pathology are unknown. Here we report the generation of a stable human RPE cell line with POLDIP2 knockout using CRISPR/Cas, providing an in vitro model to investigate the functions of POLDIP2. We conducted functional studies on the POLDIP2 knockout cell line and showed that they retained normal levels of cell proliferation, cell viability, phagocytosis and autophagy. Also, we performed RNA sequencing to profile the transcriptome of POLDIP2 knockout cells. Our results highlighted significant changes in genes involved in immune response, complement activation, oxidative damage and vascular development. We showed that loss of POLDIP2 causes a reduction in mitochondrial superoxide levels, which is consistent with the upregulation of the mitochondrial superoxide dismutase SOD2. In conclusion, this study demonstrates a novel link between POLDIP2 and SOD2, which supports a potential role of POLDIP2 in regulating oxidative stress in AMD pathology.

Degeneration in neuronal nuclei producing the neuromodulators acetylcholine and norepinephrine is a hallmark of Alzheimer’s disease (AD). Therapeutic interventions that increase acetylcholine in brain ameliorate AD symptoms in human patients, and augmenting norepinephrine restores cognitive function in mouse models of AD as well as Down Syndrome, the most frequent cause of early onset AD. A prominent cellular target of noradrenergic and potentially cholinergic signaling during states of heightened vigilance are astroglia and recent studies indicate that astroglia Ca2+ dynamics in awake mice contribute to optimal cognitive performance. Here we tested the hypothesis that vigilance-dependent Ca2+ signaling in mouse primary visual cortex astrocytes is altered in mouse models of AD and provide mechanistic insight into upstream neuromodulator signaling that shapes astrocyte Ca2+ dynamics in healthy and AD conditions. In two mouse models of AD (APPswe/PSEN1dE9 and AppNL-F KI), we consistently observed delayed and less coordinated astrocyte Ca2+ elevations in response to locomotion, a well-controlled behavioral paradigm triggering widespread Ca2+ activation in astroglia throughout the brain. Combining pharmacological and genetic manipulations, we found that noradrenergic signaling to astrocytes was facilitated by cholinergic signaling, but this neuromodulator crosstalk was impaired in AppNL-F mice. Pharmacological facilitation of norepinephrine release rescued delayed and less coordinated astrocyte Ca2+ activation in AppNL-F mice and suggests that astrocytes preserve a functional reserve that can be recruited even during late-stage disease. Our findings of delayed and less coordinated astroglia Ca2+ activation predict impaired noradrenergic signaling and may contribute to the cognitive decline in AD.

Behavioral state plays an important role in determining astroglia Ca2+ signaling. In particular, locomotion-mediated elevated vigilance has been found to trigger norepinephrine-dependent whole cell Ca2+ elevations in astroglia throughout the brain. For cerebellar Bergmann glia it has recently been found that locomotion-induced transient Ca2+ elevations depend on their α1A-adrenergic receptors. With increasing availability and implementation of locomotion as behavioral parameter it becomes important to understand the constraints of noradrenergic signaling to astroglia. Here we evaluated the effect of speed, duration and interval of locomotion on Ca2+ signals in Bergmann glia as well as cerebellar noradrenergic axon terminals. We found almost no dependence on locomotion speed, but following the initial Ca2+ transient prolonged locomotion events revealed a steady-state Ca2+ elevation. Comparison of time course and recovery of transient Bergmann glia and noradrenergic terminal Ca2+ dynamics suggested that noradrenergic terminal Ca2+ activity determines Bergmann glia Ca2+ activation and does not require noradrenergic receptor desensitization to account for attenuation during prolonged locomotion. Further, analyzing the correlation among Ca2+ dynamics within regions within the field of observation we found that coordinated activity among noradrenergic terminals accounts for fluctuations of steady-state Bergmann glia Ca2+ activity. Together, our findings will help to better understand astroglia Ca2+ dynamics during less controlled awake behavior and may guide the identification of behavioral contexts preferably dependent on astroglia Ca2+ signaling.

Genomic disorders (GDs) are associated with many comorbid outcomes, including CKD. Identification of GDs has diagnostic utility.We examined the prevalence of GDs among participants in the Chronic Kidney Disease in Children (CKiD) cohort II (We found nine out of 248 (3.6%) CKiD II participants carried a GD, replicating prior findings in pediatric CKD. We also identified GDs in 72 out of 6679 (1.1%) adult patients with CKD in the CRIC, CU-CKD, and FIND cohorts, compared with 199 out of 30,746 (0.65%) GDs in controls (OR, 1.7; 95% CI, 1.3 to 2.2). Among adults with CKD, we found recurrent GDs at the 1q21.1, 16p11.2, 17q12, and 22q11.2 loci. The 17q12 GD (diagnostic of renal cyst and diabetes syndrome) was most frequent, present in 1:252 patients with CKD and diabetes. In the PheWAS, dialysis and neuropsychiatric phenotypes were the top associations with GDs. In CRIC participants, GDs were associated with lower serum magnesium, lower educational achievement, and higher mortality risk.Undiagnosed GDs are detected both in children and adults with CKD. Identification of GDs in these patients can enable a precise genetic diagnosis, inform prognosis, and help stratify risk in clinical studies. GDs could also provide a molecular explanation for nephropathy and comorbidities, such as poorer neurocognition for a subset of patients.

BACKGROUND Recent clinical trials have demonstrated favorable outcomes associated with trans-anal colonic pull-through for rectal resection followed by delayed coloanal anastomoses (DCA), resulting in a resurgence in popularity of the technique. This meta-analysis aims to review existing literature to evaluate the postoperative complications associated with DCA, and to make comparisons with immediate coloanal anastomoses (ICA) after colorectal resection to assess the suitability of DCA as an alternative form of surgical treatment. METHODS Medline and Embase databases were reviewed from inception until 31 July 2020 in accordance with PRISMA guidelines. Single-arm studies that involved patients undergoing DCA for benign or malignant causes were selected, and meta-analysis of proportions was conducted to determine the prevalence of postoperative complications following DCA. Comparative studies comparing postoperative outcomes between DCA and ICA were also included for comparative meta-analysis. RESULTS Patients undergoing DCA were significantly less likely to require diverting stoma construction as compared to ICA (odds ratio [OR] = 0.04; confidence interval [CI]: 0.02-0.07; P

STUDY DESIGN Prospective, multicenter, partially randomized. OBJECTIVE Assess rates of complications, revision surgery, and radiation between Mazor robotic-guidance (RG) and fluoro-guidance (FG). SUMMARY OF BACKGROUND DATA Minimally invasive surgery MIS ReFRESH is the first study designed to compare RG and FG techniques in adult minimally invasive surgery (MIS) lumbar fusions. METHODS Primary endpoints were analyzed at 1 year follow-up. Analysis of variables through Cox logistic regression and a Kaplan-Meier Survival Curve of surgical complications. RESULTS Nine sites enrolled 485 patients: 374 (RG arm) and 111 (FG arm). 93.2% of patients had more than 1 year f/u. There were no differences for sex, Charlson Comorbidity Index, diabetes, or tumor. Mean age of RG patients was 59.0 versus 62.5 for FG (P = 0.009) and body mass index (BMI) was 31.2 versus 28.1 (P< 0.001). Percentage of smokers was almost double in the RG (15.2% vs. 7.2%, P = 0.029). Surgical time was similar (skin-to-skin time/no. of screws) at 24.9 minutes RG and 22.9 FG (P = 0.550). Fluoroscopy during surgery/no. of screws was 15.5 seconds RG versus 35.4 seconds FG, (15 seconds average reduction). Fluoroscopy time during instrumentation/no. of screws was 3.6 seconds RG versus 17.8 seconds FG showing an 80% average reduction of fluoro time/screw in RG (P

Poor preoperative mental health has been associated with worse outcomes after total hip (THA) and total knee arthroplasty (TKA). To fully understand these relationships, we assessed post-THA and post-TKA improvements in patient-reported mental and joint health by preoperative mental health groups.Elective cases (367 THA, 462 TKA) were subgrouped by low (25th percentile), middle (25th-74th), and high (≥75th) preoperative mental health, using Veterans RAND 12-Item Health Survey Mental Component Summary (MCS) scores. In each subgroup, we assessed the relationship between preoperative MCS and 1-year postoperative change in mental and joint health. Pairwise comparisons and multivariable regression models were applied for THA and TKA separately.Median postoperative mental health change was +14.0 points for the low-MCS THA group, +11.1 low-TKA, +2.0 middle-THA and TKA, -4.0 high-THA, and -4.9 high-TKA (between-group differences P .001). All MCS groups had improved median joint health scores, without significant between-group differences. Preoperative mental health was negatively associated with mental health improvements in all groups (B = -0.94 - -0.68, P.001-P = .01) but with improvements in joint health only in the low-THA group (B = -0.74, P = .02). Improvements in mental and joint health were positively associated for low and middle (B = 0.61-0.87, P.001), but not for high-MCS groups, with this relationship differing for the low versus high group.Patients who have low preoperative mental health experienced greater postoperative mental health improvement and similar joint health improvement compared to patients who have high preoperative mental health. Findings can guide subgroup-targeted surgical decision-making and preoperative counseling.

Focal segmental glomerulosclerosis (FSGS) is the main pathology underlying steroid-resistant nephrotic syndrome (SRNS) and a leading cause of chronic kidney disease. Monogenic forms of pediatric SRNS are predominantly caused by recessive mutations, while the contribution of de novo variants (DNVs) to this trait is poorly understood. Using exome sequencing (ES) in a proband with FSGS/SRNS, developmental delay, and epilepsy, we discovered a nonsense DNV in TRIM8, which encodes the E3 ubiquitin ligase tripartite motif containing 8. To establish whether TRIM8 variants represent a cause of FSGS, we aggregated exome/genome-sequencing data for 2,501 pediatric FSGS/SRNS-affected individuals and 48,556 control subjects, detecting eight heterozygous TRIM8 truncating variants in affected subjects but none in control subjects (p = 3.28 × 10(−11)). In all six cases with available parental DNA, we demonstrated de novo inheritance (p = 2.21 × 10(−15)). Reverse phenotyping revealed neurodevelopmental disease in all eight families. We next analyzed ES from 9,067 individuals with epilepsy, yielding three additional families with truncating TRIM8 variants. Clinical review revealed FSGS in all. All TRIM8 variants cause protein truncation clustering within the last exon between residues 390 and 487 of the 551 amino acid protein, indicating a correlation between this syndrome and loss of the TRIM8 C-terminal region. Wild-type TRIM8 overexpressed in immortalized human podocytes and neuronal cells localized to nuclear bodies, while constructs harboring patient-specific variants mislocalized diffusely to the nucleoplasm. Co-localization studies demonstrated that Gemini and Cajal bodies frequently abut a TRIM8 nuclear body. Truncating TRIM8 DNVs cause a neuro-renal syndrome via aberrant TRIM8 localization, implicating nuclear bodies in FSGS and developmental brain disease.

Background Acquired von Willebrand syndrome (AVWS) has been associated with monoclonal gammopathy of undetermined significance (MGUS), with limited data on its management. Methods We conducted a systematic literature search in Medline (Ovid), Embase, and Scopus up to September 11, 2019, for studies reporting on the management of AVWS associated with MGUS (AVWS‐MGUS). Data on patient characteristics, laboratory parameters at presentation, and clinical and laboratory outcomes were extracted. Objectives To describe the clinical presentation and outcomes of different therapeutic approaches. Results Seventy‐five studies were included in the final review, for a total of 137 patients. Most patients had von Willebrand factor ristocetin cofactor activity

Conventional predictive models are based on a combination of clinical and neuroimaging parameters using traditional statistical approaches. Emerging studies have shown that the machine learning (ML) prediction models with multiple pretreatment clinical variables have the potential to accurately prognosticate the outcomes in acute ischemic stroke (AIS) patients undergoing thrombectomy, and hence identify patients suitable for thrombectomy. This article summarizes the published studies on ML models in large vessel occlusion AIS patients undergoing thrombectomy. We searched electronic databases including PubMed from 1 January 2000 up to 14 October 2019 for studies that evaluated ML algorithms for the prediction of outcomes in stroke patients undergoing thrombectomy. We then used random-effects bivariate meta-analysis models to summarize the studies. We retained a total of five studies that evaluated ML (4 support vector machine, 1 decision tree model) with a combined cohort of 802 patients. The prevalence of good functional outcome defined by 90-day mRS of 0–2 when available. Random effects model demonstrated that the AUC was 0.846 (95% confidence interval, CI 0.686–0.902). A pooled diagnostic odds ratio of 12.6 was computed. The pooled sensitivity and specificity were 0.795 (95% CI 0.651–0.889) and 0.780 (95% CI 0.634–0.879), respectively. ML may be useful as an adjunct to clinical assessment to predict functional outcomes in AIS patients undergoing thrombectomy, and hence identify suitable patients for treatment. Further studies validating ML models in large multicenter cohorts are necessary to explore this further.

Background: Cardiomyocytes derived from pluripotent stem cells are immature. Maturation of cardiomyocytes is a multifactorial dynamic process that involves various factors in vivo that cannot be fully recapitulated in vitro. Here, we report a novel tissue engineering chamber with an integrated electrical stimulator and electrodes that will allow wireless electrical stimulation of cardiac tissue in vivo. Materials and Methods: Immunocompromised rats were implanted with tissue engineering chambers containing the stimulator and electrodes, and control chambers (chambers with electrical stimulator but without the electrodes) in the contralateral limb. Each chamber contained cardiomyocytes derived from human induced pluripotent stem cells (iPSCs). After 7 days of chamber implantation, the electrical stimulators were activated for 4 h per day, for 21 consecutive days. Results: At 4 weeks postimplantation, cardiomyocytes derived from human iPSCs survived, were assembled into compact cardiac tissue, and were perfused and vascularized by the host neovessels. Conclusion: This proof-of-principle study demonstrates the biocompatibility of the tissue engineering chamber with integrated electrical stimulator and electrodes. This could be utilized to study the influence of continuous electrical stimulation on vascularized cardiac or other tissues in vivo.