SRPK3 Is Essential for Cognitive and Ocular Development in Humans and Zebrafish, Explaining X-Linked Intellectual Disability.

OBJECTIVE: Intellectual disability is often the outcome of neurodevelopmental disorders and is characterized by significant impairments in intellectual and adaptive functioning. X-linked intellectual disability (XLID) is a subset of these disorders caused by genetic defects on the X chromosome, affecting about 2 out of 1,000 males. In syndromic form, it leads to a broad range of cognitive, behavioral, ocular, and physical disabilities. METHODS: Employing exome or genome sequencing, here we identified 4 missense variants (c.475C > G; p.H159D, c.1373C > A; p.T458N, and c.1585G > A; p.E529K, c.953C > T; p.S318L) and a putative truncating variant (c.1413_1414del; p.Y471*) in the SRPK3 gene in 9 XLID patients from 5 unrelated families. To validate SRPK3 as a novel XLID gene, we established a knockout (KO) model of the SRPK3 orthologue in zebrafish. RESULTS: The 8 patients ascertained postnatally shared common clinical features including intellectual disability, agenesis of the corpus callosum, abnormal eye movement, and ataxia. A ninth case, ascertained prenatally, had a complex structural brain phenotype. Together, these data indicate a pathological role of SRPK3 in neurodevelopmental disorders. In post-fertilization day 5 larvae (free swimming stage), KO zebrafish exhibited severe deficits in eye movement and swim bladder inflation, mimicking uncontrolled ocular movement and physical clumsiness observed in human patients. In adult KO zebrafish, cerebellar agenesis and behavioral abnormalities were observed, recapitulating human phenotypes of cerebellar atrophy and intellectual disability. INTERPRETATION: Overall, these results suggest a crucial role of SRPK3 in the pathogenesis of syndromic X-linked intellectual disability and provide new insights into brain development, cognitive and ocular dysfunction in both humans and zebrafish. ANN NEUROL 2024.

FcRγ- NK Cell Induction by Specific Cytomegalovirus and Expansion by Subclinical Viral Infections in Rhesus Macaques.

"Adaptive" NK cells, characterized by FcRγ deficiency and enhanced responsiveness to Ab-bound, virus-infected cells, have been found in certain hCMV-seropositive individuals. Because humans are exposed to numerous microbes and environmental agents, specific relationships between hCMV and FcRγ-deficient NK cells (also known as g-NK cells) have been challenging to define. Here, we show that a subgroup of rhesus CMV (RhCMV)-seropositive macaques possesses FcRγ-deficient NK cells that stably persist and display a phenotype resembling human FcRγ-deficient NK cells. Moreover, these macaque NK cells resembled human FcRγ-deficient NK cells with respect to functional characteristics, including enhanced responsiveness to RhCMV-infected target in an Ab-dependent manner and hyporesponsiveness to tumor and cytokine stimulation. These cells were not detected in specific pathogen-free (SPF) macaques free of RhCMV and six other viruses; however, experimental infection of SPF animals with RhCMV strain UCD59, but not RhCMV strain 68-1 or SIV, led to induction of FcRγ-deficient NK cells. In non-SPF macaques, coinfection by RhCMV with other common viruses was associated with higher frequencies of FcRγ-deficient NK cells. These results support a causal role for specific CMV strain(s) in the induction of FcRγ-deficient NK cells and suggest that coinfection by other viruses further expands this memory-like NK cell pool.

Ultrasmall 2D Sn-Doped MAPbBr3 Nanoplatelets Enable Bright Pure-Blue Emission.

Synthesis of perovskites that exhibit pure-blue emission with high photoluminescence quantum yield (PLQY) in both nanocrystal solutions and nanocrystal-only films presents a significant challenge. In this work, a room-temperature method is developed to synthesize ultrasmall, monodispersed, Sn-doped methylammonium lead bromide (MAPb1- xSnxBr3) perovskite nanoplatelets (NPLs) in which the strong quantum confinement effect endows pure blue emission (460 nm) and a high quantum yield (87%). Post-treatment using n-hexylammonium bromide (HABr) repaired surface defects and thus substantially increased the stability and PLQY (80%) of the NPL films. Concurrently, high-precision patterned films (200-µm linewidth) are successfully fabricated by using cost-effective spray-coating technology. This research provides a novel perspective for the preparation of high PLQY, highly stable, and easily processable perovskite nanomaterials.

Development of oxidative stress-associated disease models using feto-maternal interface organ-on-a-chip.

Oxidative stress (OS) and inflammation arising from cellular derangements at the fetal membrane-decidual interface (feto-maternal interface [FMi]) is a major antecedent to preterm birth (PTB). However, it is impractical to study OS-associated FMi disease state during human pregnancy, and thus it is difficult to develop strategies to reduce the incidences of PTB. A microfluidic organ-on-chip model (FMi-OOC) that mimics the in vivo structure and functions of FMi in vitro was developed to address this challenge. The FMi-OOC contained fetal (amnion epithelial, mesenchymal, and chorion) and maternal (decidua) cells cultured in four compartments interconnected by arrays of microchannels to allow independent but interconnected co-cultivation. Using this model, we tested the effects of OS and inflammation on both fetal (fetal → maternal) and maternal (maternal → fetal) sides of the FMi and determined their differential impact on PTB-associated pathways. OS was induced using cigarette smoke extract (CSE) exposure. The impacts of OS were assessed by measuring cell viability, disruption of immune homeostasis, epithelial-to-mesenchymal transition (EMT), development of senescence, and inflammation. CSE propagated (LC/MS-MS analysis for nicotine) over a 72-hour period from the maternal to fetal side, or vice versa. However, they caused two distinct pathological effects on the maternal and fetal cells. Specifically, fetal OS induced cellular pathologies and inflammation, whereas maternal OS caused immune intolerance. The pronounced impact produced by the fetus supports the hypothesis that fetal inflammatory response is a mechanistic trigger for parturition. The FMi disease-associated changes identified in the FMi-OOC suggest the unique capability of this in vitro model in testing in utero conditions.

Uniform sized cancer spheroids production using hydrogel-based droplet microfluidics: a review.

Three-dimensional (3D) cell culture models have been extensively utilized in various mechanistic studies as well as for drug development studies as superior in vitro platforms than conventional two-dimensional (2D) cell culture models. This is especially the case in cancer biology, where 3D cancer models, such as spheroids or organoids, have been utilized extensively to understand the mechanisms of cancer development. Recently, many sophisticated 3D models such as organ-on-a-chip models are emerging as advanced in vitro models that can more accurately mimic the in vivo tissue functions. Despite such advancements, spheroids are still considered as a powerful 3D cancer model due to the relatively simple structure and compatibility with existing laboratory instruments, and also can provide orders of magnitude higher throughput than complex in vitro models, an extremely important aspects for drug development. However, creating well-defined spheroids remain challenging, both in terms of throughputs in generation as well as reproducibility in size and shape that can make it challenging for drug testing applications. In the past decades, droplet microfluidics utilizing hydrogels have been highlighted due to their potentials. Importantly, core-shell structured gel droplets can avoid spheroid-to-spheroid adhesion that can cause large variations in assays while also enabling long-term cultivation of spheroids with higher uniformity by protecting the core organoid area from external environment while the outer porous gel layer still allows nutrient exchange. Hence, core-shell gel droplet-based spheroid formation can improve the predictivity and reproducibility of drug screening assays. This review paper will focus on droplet microfluidics-based technologies for cancer spheroid production using various gel materials and structures. In addition, we will discuss emerging technologies that have the potential to advance the production of spheroids, prospects of such technologies, and remaining challenges.

A dynamic flow fetal membrane organ-on-a-chip system for modeling the effects of amniotic fluid motion.

Fetal membrane (amniochorion), the innermost lining of the intrauterine cavity, surround the fetus and enclose amniotic fluid. Unlike unidirectional blood flow, amniotic fluid subtly rocks back and forth, and thus, the innermost amnion epithelial cells are continuously exposed to low levels of shear stress from fluid undulation. Here, we tested the impact of fluid motion on amnion epithelial cells (AECs) as a bearer of force impact and their potential vulnerability to cytopathologic changes that can destabilize fetal membrane functions. A previously developed amnion membrane (AM) organ-on-chip (OOC) was utilized but with dynamic flow to culture human fetal amnion membrane cells. The applied flow was modulated to perfuse culture media back and forth for 48 h to mimic fluid motion. A static culture condition was used as a negative control, and oxidative stress (OS) condition was used as a positive control representing pathophysiological changes. The impacts of fluidic motion were evaluated by measuring cell viability, cellular transition, and inflammation. Additionally, scanning electron microscopy (SEM) imaging was performed to observe microvilli formation. The results show that regardless of the applied flow rate, AECs and AMCs maintained their viability, morphology, innate meta-state, and low production of pro-inflammatory cytokines. E-cadherin expression and microvilli formation in the AECs were upregulated in a flow rate-dependent fashion; however, this did not impact cellular morphology or cellular transition or inflammation. OS treatment induced a mesenchymal morphology, significantly higher vimentin to cytokeratin 18 (CK-18) ratio, and pro-inflammatory cytokine production in AECs, whereas AMCs did not respond in any significant manner. Fluid motion and shear stress, if any, did not impact AEC cell function and did not cause inflammation. Thus, when using an amnion membrane OOC model, the inclusion of a dynamic flow environment is not necessary to mimic in utero physiologic cellular conditions of an amnion membrane.

Epigenetic modification and antibody-dependent expansion of memory-like NK cells in human cytomegalovirus-infected individuals.

Long-lived "memory-like" NK cells have been identified in individuals infected by human cytomegalovirus (HCMV), but little is known about how the memory-like NK cell pool is formed. Here, we have shown that HCMV-infected individuals have several distinct subsets of memory-like NK cells that are often deficient for multiple transcription factors and signaling proteins, including tyrosine kinase SYK, for which the reduced expression was stable over time and correlated with epigenetic modification of the gene promoter. Deficient expression of these proteins was largely confined to the recently discovered FcRγ-deficient NK cells that display enhanced antibody-dependent functional activity. Importantly, FcRγ-deficient NK cells exhibited robust preferential expansion in response to virus-infected cells (both HCMV and influenza) in an antibody-dependent manner. These findings suggest that the memory-like NK cell pool is shaped and maintained by a mechanism that involves both epigenetic modification of gene expression and antibody-dependent expansion.

Risk factors for delayed hemothorax in patients with rib fracture in the emergency department.

OBJECTIVES: Although rib fractures are a risk factor, not all rib fracture patients will develop delayed hemothorax. This study aimed to evaluate risk factors which can identify rib fracture patients in the emergency department who may develop delayed hemothorax. METHODS: Adult patients seen in the emergency room between January 2016 and February 2021 with rib fractures caused by blunt chest trauma were included in this retrospective observational study. Patients who underwent chest tube insertion within 2 days and those without follow-up chest radiographs within 2-30 days were excluded. We used a stepwise backward-elimination multivariable logistic regression model for analysis. RESULTS: A total of 202 patients were included in this study. The number of total (P < 0.001), lateral (P = 0.019), and displaced (P < 0.001) rib fractures were significantly associated with delayed hemothorax. Lung contusions (P = 0.002), and initial minimal hemothorax (P < 0.001) and pneumothorax (P < 0.001) were more frequently associated with delayed hemothorax. Age (adjusted odds ratio (aOR) 1.03, 95% confidence interval (CI) 1.00-1.06, P = 0.022), mechanical ventilator use (aOR 9.67, 95% CI 1.01-92.75, P = 0.049), initial hemothorax (aOR 2.21, 95% CI 1.05-4.65, P = 0.037) and pneumothorax (aOR 2.99, 95% CI 1.36-6.54, P = 0.006), and displaced rib fractures (aOR 3.51, 95% CI 1.64-7.53, P = 0.001) were independently associated with delayed hemothorax. CONCLUSIONS: Age, mechanical ventilation, initial hemo- or pneumothorax, and displaced rib fractures were risk factors for delayed hemothorax. Patients with these risk factors, and especially those with ≥2 displaced rib fractures, require close chest radiography follow-up of 2-30 days after the initial trauma.

Predicting septic shock in patients with sepsis at emergency department triage using systolic and diastolic shock index.

INTRODUCTION: Identifying patients with at a high risk of progressing to septic shock is essential. Due to systemic vasodilation in the pathophysiology of septic shock, the use of diastolic blood pressure (DBP) has emerged. We hypothesized that the initial shock index (SI) and diastolic SI (DSI) at the emergency department (ED) triage can predict septic shock. METHOD: This observational study used the prospectively collected sepsis registry. The primary outcome was progression to septic shock. Secondary outcomes were the time to vasopressor requirement, vasopressor dose, and severity according to SI and DSI. Patients were classified by tertiles according to the first principal component of shock index and diastolic shock index. RESULTS: A total of 1267 patients were included in the analysis. The area under the receiver operating characteristic curve (AUC) for predicting progression to septic shock for DSI was 0.717, while that for SI was 0.707. The AUC for predicting progression to septic shock for DSI and SI were significantly higher than those for conventional early warning scores. Middle tertile showed adjusted Odd ratio (aOR) of 1.448 (95% CI 1.074-1.953), and that of upper tertile showed 3.704 (95% CI 2.299-4.111). CONCLUSION: The SI and DSI were significant predictors of progression to septic shock. Our findings suggest an association between DSI and vasopressor requirement. We propose stratifying lower tertile as being at low risk, middle tertile as being at intermediate risk, and upper tertile as being at high risk of progression to septic shock. This system can be applied simply at the ED triage.

Presynaptic coupling by electrical synapses coordinates a rhythmic behavior by synchronizing the activities of a neuron pair.

Electrical synapses are specialized structures that mediate the flow of electrical currents between neurons and have well known roles in synchronizing the activities of neuronal populations, both by mediating the current transfer from more active to less active neurons and by shunting currents from active neurons to their less active neighbors. However, how these positive and negative functions of electrical synapses are coordinated to shape rhythmic synaptic outputs and behavior is not well understood. Here, using a combination of genetics, behavioral analysis, and live calcium imaging in Caenorhabditis elegans, we show that electrical synapses formed by the gap junction protein INX-1/innexin couple the presynaptic terminals of a pair of motor neurons (AVL and DVB) to synchronize their activation in response to a pacemaker signal. Live calcium imaging reveals that inx-1/innexin mutations lead to asynchronous activation of AVL and DVB, due, in part, to loss of AVL-mediated activation of DVB by the pacemaker. In addition, loss of inx-1 leads to the ectopic activation of DVB at inappropriate times during the cycle through the activation of the L-type voltage-gated calcium channel EGL-19. We propose that electrical synapses between AVL and DVB presynaptic terminals function to ensure the precise and robust execution of a specific step in a rhythmic behavior by both synchronizing the activities of presynaptic terminals in response to pacemaker signaling and by inhibiting their activation in between cycles when pacemaker signaling is low.

A 6-Week Program to Strengthen Resiliency Among Women With Metastatic Cancer: A Randomized Clinical Trial.

PURPOSE: The objective of this study was to evaluate the effect of an intervention (Growing Resilience And CouragE; GRACE) on spiritual well-being, quality of life, and general well-being in women with metastatic cancers reporting existential or spiritual distress. PATIENTS AND METHODS: Prospective, randomized, wait-list control clinical trial. Women with metastatic cancer experiencing existential or spiritual concerns were randomized to GRACE or waitlist control. Survey data were collected at baseline, end of program, and 1-month follow-up. Participants included English-speaking women, 18 or older, with metastatic cancer, existential or spiritual concerns, and reasonable medical stability. Eighty-one women were assessed for eligibility; 10 were excluded (not meeting exclusion criteria, refusal to participate, and death). The primary outcome was spiritual well-being measured pre- and post-program. Secondary measures assessed quality of life, anxiety, depression, hopelessness, and loneliness. RESULTS: Seventy-one women (aged 47-72) were enrolled (GRACE n = 37, waitlist control n = 34). GRACE participants demonstrated significant improvements in spiritual well-being compared to control at end of program (parameter estimate (PE), 16.67, 95% CI, 13.17, 20.16) and 1-month follow-up (PE, 10.31, 95% CI, 6.73, 13.89). Additionally, significant improvements were demonstrated in quality of life at the end of program (PE, 8.51, 95% CI, 4.26, 12.76) and 1-month follow-up (PE, 6.17, 95% CI, 1.75, 10.58). GRACE participants also demonstrated improved depression and hopelessness at follow-up, as well as improved anxiety. CONCLUSIONS: Findings suggest the value of evidence-based psychoeducational and experiential interventions for improving the well-being and quality of life of women with advanced cancer. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02707510.

Derivation and External Validation of Machine Learning-Based Model for Detection of Pancreatic Cancer.

INTRODUCTION: There is currently no widely accepted approach to screening for pancreatic cancer (PC). We aimed to develop and validate a risk prediction model for pancreatic ductal adenocarcinoma (PDAC), the most common form of PC, across 2 health systems using electronic health records. METHODS: This retrospective cohort study consisted of patients aged 50-84 years having at least 1 clinic-based visit over a 10-year study period at Kaiser Permanente Southern California (model training, internal validation) and the Veterans Affairs (VA, external testing). Random survival forests models were built to identify the most relevant predictors from >500 variables and to predict risk of PDAC within 18 months of cohort entry. RESULTS: The Kaiser Permanente Southern California cohort consisted of 1.8 million patients (mean age 61.6) with 1,792 PDAC cases. The 18-month incidence rate of PDAC was 0.77 (95% confidence interval 0.73-0.80)/1,000 person-years. The final main model contained age, abdominal pain, weight change, HbA1c, and alanine transaminase change (c-index: mean = 0.77, SD = 0.02; calibration test: P value 0.4, SD 0.3). The final early detection model comprised the same features as those selected by the main model except for abdominal pain (c-index: 0.77 and SD 0.4; calibration test: P value 0.3 and SD 0.3). The VA testing cohort consisted of 2.7 million patients (mean age 66.1) with an 18-month incidence rate of 1.27 (1.23-1.30)/1,000 person-years. The recalibrated main and early detection models based on VA testing data sets achieved a mean c-index of 0.71 (SD 0.002) and 0.68 (SD 0.003), respectively. DISCUSSION: Using widely available parameters in electronic health records, we developed and externally validated parsimonious machine learning-based models for detection of PC. These models may be suitable for real-time clinical application.

Method to fabricate round cross-sectional channel using thermal expansion of air for passive flow regulators.

We present a novel method for fabricating round cross-sectional channels for autoregulatory pressure regulators. The application of previously reported methods in multilayered soft lithography using three-dimensional printed molds is challenging. Herein, we used a thermal expansion technique to create round cross-sectional channels in replica layers using air in the cavity space of a master mold. The width and height of the round channel in the replica could be adjusted in the range of 80-300 and 3-57 µm, respectively, by varying the precuring time of the replica in the gel state and adjusting the cavity size of the master mold. We successfully fabricated a pressure regulator with a round cross-sectional channel, achieving a constant output pressure at a low threshold input pressure. Our device exhibited superior performance, with a constant output pressure at a threshold input pressure of less than 77%, compared to a device with a rectangular cross-sectional channel. Our method has significant potential for application in the fabrication of integrated microfluidic systems with round cross-sectional channels.

Modeling ascending Ureaplasma parvum infection through the female reproductive tract using vagina-cervix-decidua-organ-on-a-chip and feto-maternal interface-organ-on-a-chip.

Genital mycoplasmas can break the cervical barrier and cause intraamniotic infection and preterm birth. This study developed a six-chamber vagina-cervix-decidua-organ-on-a-chip (VCD-OOC) that recapitulates the female reproductive tract during pregnancy with culture chambers populated by vaginal epithelial cells, cervical epithelial and stromal cells, and decidual cells. Cells cultured in VCD-OOC were characterized by morphology and immunostaining for cell-specific markers. We transferred the media from the decidual cell chamber of the VCD-OOC to decidual cell chamber in feto-maternal interface organ-on-a-chip (FMi-OOC), which contains the fetal membrane layers. An ascending Ureaplasma parvum infection was created in VCD-OOC. U. parvum was monitored for 48 h post-infection with their cytotoxicity (LDH assay) and inflammatory effects (multiplex cytokine assay) in the cells tested. An ascending U. parvum infection model of PTB was developed using CD-1 mice. The cell morphology and expression of cell-specific markers in the VCD-OOC mimicked those seen in lower genital tract tissues. U. parvum reached the cervical epithelial cells and decidua within 48 h and did not cause cell death in VCD-OOC or FMi-OOC cells. U. parvum infection promoted minimal inflammation, while the combination of U. parvum and LPS promoted massive inflammation in the VCD-OOC and FMi-OOC cells. In the animal model, U. parvum vaginal inoculation of low-dose U. parvum did not result in PTB, and even a high dose had only some effects on PTB (20%). However, intra-amniotic injection of U. parvum resulted in 67% PTB. We report the colonization of U. parvum in various cell types; however, inconsistent, and low-grade inflammation across multiple cell types suggests poor immunogenicity induced by U. parvum.

A 5.8 GHz 1.8 V +20 dBm 32.5% PAE Power Amplifier for a Short-Range Over-the-Air WPT Application.

This paper presents a 5.8 GHz differential cascode power amplifier for an over-the-air wireless power transfer application. Over-the-air wireless power transfer provides a variety of benefits in several applications such as the Internet of Things and medical implantation applications. The proposed PA features two fully differentially active stages with a custom-designed transformer to provide a single-ended output. The custom-made transformer shows a high quality factor, as high as 11.6 and 11.2 for the primary and secondary sides at 5.8 GHz. Fabricated using a standard 180 nm CMOS process, the amplifier achieves input and output matching of -14.7 dB and -29.7 dB, respectively. To achieve a high power level and efficiency, accurate optimization through power matching, Power Added Efficiency (PAE), and the design of the transformer are carried out while the supply voltage is limited to 1.8 V. Measurement results show a 20 dBm output power with a PAE as high as 32.5%, which makes the PA suitable for application, and it can be implanted while arrayed with various antenna arrays. Finally, a FOM is introduced to compare the performance of the work with similar works in the literature.

Characteristics of rib fracture patients who require chest computed tomography in the emergency department.

BACKGROUND: The disadvantages and complications of computed tomography (CT) can be minimized if CT is performed in rib fracture patients with high probability of intra-thoracic and intra-abdominal injuries and CT is omitted in rib fracture patients with low probability of intra-thoracic and intra-abdominal injuries. This study aimed to evaluate the factors that can identify patients with rib fractures with intra-thoracic and intra-abdominal injuries in the emergency department among patients with rib fracture. METHODS: This retrospective observational study included adult patients (age ≥ 18 years) diagnosed with rib fracture on chest radiography prior to chest CT due to blunt chest trauma in the emergency department who underwent chest CT from January 2016 to February 2021. The primary outcomes were intra-thoracic and intra-abdominal injuries that could be identified on a chest CT. Multivariate logistic regression analysis was performed. RESULTS: Among the characteristics of rib fractures, the number of rib fractures was greater (5.0 [3.0-7.0] vs. 2.0 [1.0-3.0], p < 0.001), bilateral rib fractures were frequent (56 [20.1%] vs. 12 [9.8%], p = 0.018), and lateral and posterior rib fracture was more frequent (lateral rib fracture: 160 [57.3%] vs. 25 [20.5%], p < 0.001; posterior rib fracture: 129 [46.2%] vs. 21 [17.2%], p < 0.001), and displacement was more frequent (99 [35.5%] vs. 6 [6.6%], p < 0.001) in the group with intra-thoracic and intra-abdominal injuries than in the group with no injury. The number of rib fractures (adjusted odds ratio [aOR], 1.44; 95% confidence interval [CI], 1.16-1.78; p = 0.001), lateral rib fracture (aOR, 2.80; 95% CI, 1.32-5.95; p = 0.008), and posterior rib fracture (aOR, 3.18; 95% CI, 1.45-6.94; p = 0.004) were independently associated with intra-thoracic and intra-abdominal injuries. The optimal cut-off for the number of rib fractures on the outcome was three. The number of rib fractures ≥ 3 (aOR, 3.01; 95% CI, 1.35-6.71; p = 0.007) was independently associated with intra-thoracic and intra-abdominal injuries. CONCLUSION: In patients with rib fractures due to blunt trauma, those with lateral or posterior rib fractures, those with ≥ 3 rib fractures, and those requiring O2 supplementation require chest CT to identify significant intra-thoracic and intra-abdominal injuries in the emergency department.

Mechanical Timer-Actuated Fluidic Dispensing System: Applications to an Automated Multistep Lateral Flow Immunoassay with High Sensitivity.

In this study, we present a fluidic dispensing system that can automate the sequential fluidic delivery of multiple reagents for lateral flow assays. Highly sensitive assays typically require multiple solution-based sequences, including washing steps and signal amplification. However, implementation of these types of sequences on an automated and highly sensitive point-of-care testing (POCT) platform remains challenging. Our platform consists of two disposable cartridges with reagent chambers and a test strip and an instrument that has a mechanical timer to actuate the cam-follower-gear components. The timer rotation sequentially shifts the position of the chambers and loads the reagents to the test paper strip. The dispensing intervals are controlled at a variation of <1% within a total actuation time of 60 min. Unlike other POCT devices, the timing of fluid delivery in our timer-actuated platform is not dependent on the selection of substrates and reagents, and the unique approach to fluidic delivery results in no reagent overlap or carryover, minimal reagent loss, and highly accurate fluidic timing control for highly sensitive solution-based assays. As a model application, the proposed platform applies a gold enhancement solution to amplify the detection signal and detect prostate-specific antigen with a limit of detection of 86 pg/mL within 27 min. This platform provides an opportunity for solution-based POCT applications with high sensitivity, thereby satisfying the requirement for user-friendly operations in resource-limited settings.

Novel Endoscopic Polypectomy Surveillance Technique for Fundic Gland Polyps in Familial Adenomatous Polyposis Can Improve Early Detection of Dysplasia and Gastric Cancer.

INTRODUCTION: Fundic gland polyps (FGPs) are commonly found in patients with familial adenomatous polyposis (FAP) and are considered benign. Biopsies are not routinely performed, and conventional forceps may be time-consuming and/or yield nonrepresentative histology. The purpose of this study was to evaluate the role of a novel endoscopic polypectomy surveillance (EPS), a large volume cold-snare polypectomy technique of random FGPs, in the incidence of dysplasia and gastric cancer (GC) in FAP. METHODS: This is a retrospective longitudinal cohort of patients with FAP referred to a tertiary care center for duodenal adenoma surveillance and who underwent EPS of FGPs between 2001 and 2019. Demographic, endoscopic, and clinicopathologic information was reviewed. RESULTS: Thirty-five patients with FAP were identified at initial endoscopy by the mean age of 43.4 years (±12.8). One hundred thirteen surveillance endoscopies were performed in total using EPS. Dysplasia of FGPs was present on initial esophagogastroduodenoscopy in 7 patients (20%), and 13 additional patients (46.4%) progressed to low-grade dysplasia. Three patients (15%) who subsequently had progression to GC were found to have signet ring cell cancer within the foci of FGPs through EPS. One patient presented as metastatic GC. Progression from nondysplastic FGP to low-grade dysplasia occurred over 63 months (±46.3) with further progression to GC over 34 months (±8.5). Endoscopic risk factors for cancer were polyps >10 mm in size ( P < 0.001) and carpeting of polyps ( P < 0.001). The 5-year cumulative incidence of developing dysplasia was 35.7%. DISCUSSION: We identified that the incidence of dysplasia and GC is higher than previously reported in patients with FAP. Our study used a novel EPS technique and was able to identify GC within the foci of FGPs. Upper endoscopic guidelines should include a more rigorous sampling method for FGPs, such as EPS, to optimize early detection of dysplasia and GC.

Association of Preoperative Sarcopenia with Adverse Outcomes of Breast Reconstruction Using Deep Inferior Epigastric Artery Perforator Flap.

BACKGROUND: Sarcopenia, defined as a significant loss of skeletal muscle mass and function, is suggested to be associated with an increased risk of complications after various surgical interventions. However, evidence regarding sarcopenia in microsurgical breast reconstruction has been lacking. The present study was designed to evaluate the association between preoperative sarcopenia and adverse outcomes in deep inferior epigastric perforator (DIEP) flap-based breast reconstruction. METHODS: Patients who underwent breast reconstruction using DIEP flap between 2009 and 2018 were reviewed. Sarcopenia was defined as a skeletal muscle index < 38.5 cm2/m2, calculated by normalizing the cross-sectional area of the skeletal muscle, measured at the level of the third lumbar vertebra based on preoperative computed tomography angiography, to patient height. Postoperative complication rates were compared between patients with sarcopenia and those without it. Independent association of sarcopenia with complication profiles were evaluated. Further analyses were conducted using propensity score matching. RESULTS: In total, 557 patients were analyzed, of which 154 (27.6%) had preoperative sarcopenia. The sarcopenia group had a significantly lower body mass index, a lower elevated flap weight, and greater use of bipedicled flaps compared to the nonsarcopenia group. Complications developed in 128 patients (23.0%) and were more prevalent in the sarcopenia group. Preoperative sarcopenia was associated with a significantly higher rate of complications, including breast hematoma, breast wound problems, abdominal functional weakness, and reoperation in the multivariable analyses. Similar associations were observed in the propensity score matching analysis. CONCLUSIONS: Preoperative sarcopenia appears to be associated with adverse outcomes in DIEP flap-based breast reconstruction.

Psychosocial Interventions for Patients With Heart Failure and Their Impact on Depression, Anxiety, Quality of Life, Morbidity, and Mortality: A Systematic Review and Meta-Analysis.

OBJECTIVE: The purpose of this systematic review and meta-analysis was to evaluate the ability of psychosocial interventions to reduce depression and anxiety, improve quality of life, and reduce hospitalization and mortality rates in patients with heart failure. METHODS: Studies of psychosocial interventions published from 1970 to 2021 were identified through four databases (PubMed, Ovid MEDLINE, PsycINFO, Cochrane). Two authors independently conducted a focused analysis and reached a final consensus on the studies to include, followed by a quality check by a third author. A risk of bias assessment was conducted. RESULTS: Twenty-three studies were identified, but only 15 studies of mostly randomized controlled trials with a total of 1370 patients with heart failure were included in the meta-analysis. Interventions were either cognitive behavioral therapy (CBT) or stress management. The pooled intervention effect was in favor of the intervention for depression (combined difference in standardized mean change [DSMC]: -0.41; 95% confidence interval [CI] = -0.66 to -0.17; p = .001) and anxiety (combined DSMC: -0.33; 95% CI = -0.51 to -0.15; p < .001) but was only a trend for quality of life (combined DSMC: 0.14; 95% CI = -0.00 to 0.29; p = .053). Evidence was limited that interventions produced lower rates of hospitalization (5 of 5 studies showing a beneficial effect) or death (1 of 5 with a beneficial effect). CONCLUSIONS: CBT and stress management interventions significantly reduced depression and anxiety compared with control conditions. CBT significantly improved quality of life compared with controls, but stress management did not. Longer treatment duration seemed to be an important factor related to treatment success.