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Ectopic pregnancy is increasing in incidence. Nevertheless, there is wide availability of tools for early diagnosis and advances in management. Though it is not a leading cause of maternal mortality, it significantly causes morbidity and jeopardizes reproductive outcome in women desirous of fertility. To determine incidence, risk factors, symptoms, signs, type of ectopic pregnancy and management. This is a one-year prospective, descriptive study conducted in Department of Obstetrics and Gynaecology, Sri Ramachandra Medical College and Research Institute, Porur, Chennai. There were 119 ectopic pregnancies during the study period. The incidence of ectopic pregnancy is 2.81/100 deliveries. Ectopic pregnancy was common in 26–30 years, the minimum age at diagnosis was 18 years and maximum age was 40 years. Fourteen women had previous one ectopic pregnancy. Four had previous two ectopic pregnancies. Previous cesarean and treatment for infertility were the commonest risk factors. The classic triad was present in only 27.7% of patients. Fourteen patients presented with shock. Five women were diagnosed even before they missed their periods. Success rate of medical treatment with methotrexate is 83.33%. Tubal pregnancy was the commonest type, and ampulla was the commonest site. Right side was affected more than left side. Thirty-three patients (27.7%) required blood transfusion. Seven developed morbidity. After 1-year follow-up of 68 women who were desirous of fertility, five women have become pregnant subsequently with intrauterine gestation.

Next-generation sequencing (NGS) studies have demonstrated that co-occurring sporadic endometrioid endometrial carcinoma (EEC) and endometrioid ovarian carcinoma (EOC) are clonally related, suggesting that they originate from a single primary tumor. Despite clonality, synchronous EEC and EOC when diagnosed at early stage behave indolently, similar to isolated primary EEC or isolated primary EOC. In the present study, we compared the DNA methylation signatures of co-occurring EEC and EOC with those of isolated primary EEC and isolated primary EOC. We also performed targeted NGS to assess the clonal relatedness of 7 co-occurring EEC and EOC (4 synchronous EEC and EOC and 3 metastatic EEC based on pathologic criteria). NGS confirmed a clonal relationship in all co-occurring EEC and EOC. DNA methylation profiling showed distinct epigenetic signatures of isolated primary EEC and isolated primary EOC. Endometrial tumors from co-occurring EEC and EOC clustered with isolated primary EEC while their ovarian counterparts clustered with isolated primary EOC. Three co-occurring EEC and EOC cases with peritoneal lesions showed a closer epigenetic signature and copy number variation profile between the peritoneal lesion and EOC than EEC. In conclusion, synchronous sporadic EEC and EOC are clonally related but demonstrate a shift in DNA methylation signatures between ovarian and endometrial tumors as well as epigenetic overlap between ovarian and peritoneal tumors. Our results suggest that tumor microenvironment in the ovary may play a role in epigenetic modulation of metastatic EEC.

Genetic studies have identified recurrent somatic mutations in acute myeloid leukemia (AML) patients, including in the Wilms’ tumor 1 (WT1) gene. The molecular mechanisms by which WT1 mutations contribute to leukemogenesis have not yet been fully elucidated. We investigated the role of Wt1 gene dosage in steady-state and pathologic hematopoiesis. Wt1 heterozygous loss enhanced stem cell self-renewal in an age-dependent manner, which increased stem cell function over time and resulted in age-dependent leukemic transformation. Wt1-haploinsufficient leukemias were characterized by progressive genetic and epigenetic alterations, including those in known leukemia-associated alleles, demonstrating a requirement for additional events to promote hematopoietic transformation. Consistent with this observation, we found that Wt1 depletion cooperates with Flt3-ITD mutation to induce fully penetrant AML. Our studies provide insight into mechanisms of Wt1-loss leukemogenesis and into the evolutionary events required to induce transformation of Wt1-haploinsufficient stem/progenitor cells.

IMPORTANCE: Although low-income populations have more eye problems, whether they face greater difficulty obtaining eye care appointments is unknown. OBJECTIVE: To compare rates of obtaining eye care appointments and appointment wait times for those with Medicaid vs those with private insurance. DESIGN, SETTING, AND PARTICIPANTS: In this prospective, cohort study conducted from January 1, 2017, to July 1, 2017, researchers made telephone calls to a randomly selected sample of vision care professionals in Michigan and Maryland stratified by neighborhood (urban vs rural) and professional type (ophthalmologist vs optometrist) to request the first available appointment. Appointments were sought for an adult needing a diabetic eye examination and a child requesting a routine eye examination for a failed vision screening. Researchers called each practice twice, once requesting an appointment for a patient with Medicaid and the other time for a patient with Blue Cross Blue Shield (BCBS) insurance, and asked whether the insurance was accepted and, if so, when the earliest available appointment could be scheduled. MAIN OUTCOMES AND MEASURES: Rate of successfully made appointments and mean wait time for the first available appointment. RESULTS: A total of 603 telephone calls were made to 330 eye care professionals (414 calls [68.7%] to male and 189 calls [31.3%] to female eye care professionals). The sample consisted of ophthalmologists (303 [50.2%]) and optometrists (300 [49.8%]) located in Maryland (322 [53.4%]) and Michigan (281 [46.6%]). The rates of successfully obtaining appointments among callers were 61.5% (95% CI, 56.0%-67.0%) for adults with Medicaid and 79.3% (95% CI, 74.7%-83.9%) for adults with BCBS (P < .001) and 45.4% (95% CI, 39.8%-51.0%) for children with Medicaid and 62.5% (95% CI, 57.1%-68.0%) for children with BCBS (P < .001). Mean wait time did not vary significantly between the BCBS and Medicaid groups for both adults and children. Adults with Medicaid had significantly decreased odds of receiving an appointment compared with those with BCBS (odds ratio [OR], 0.41; 95% CI, 0.28-0.59; P < .001) but had increased odds of obtaining an appointment if they were located in Michigan vs Maryland (OR, 2.40; 95% CI, 1.49-3.87; P < .001) or with an optometrist vs an ophthalmologist (OR, 1.91; 95% CI, 1.31-2.79; P < .001). Children with Medicaid had significantly decreased odds of receiving an appointment compared with those with BCBS (OR, 0.41; 95% CI, 0.28-0.60; P < .001) but had increased odds of obtaining an appointment if they were located in Michigan vs Maryland (OR, 1.68; 95% CI, 1.04-2.73; P = .03) or with an optometrist vs an ophthalmologist (OR, 8.00; 95% CI, 5.37-11.90; P < .001). CONCLUSIONS AND RELEVANCE: Callers were less successful in trying to obtain eye care appointments with Medicaid than with BCBS, suggesting a disparity in access to eye care based on insurance status, although confounding factors may have contributed to this finding. Improving access to eye care professionals for those with Medicaid may improve health outcomes and decrease health care spending in the long term.

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ObjectiveTo investigate the efficacy and safety of dietary supplements for patients with osteoarthritis.DesignAn intervention systematic review with random effects meta-analysis and meta-regression.Data sourcesMEDLINE, EMBASE, Cochrane Register of Controlled Trials, Allied and Complementary Medicine and Cumulative Index to Nursing and Allied Health Literature were searched from inception to April 2017.Study eligibility criteriaRandomised controlled trials comparing oral supplements with placebo for hand, hip or knee osteoarthritis.ResultsOf 20 supplements investigated in 69 eligible studies, 7 (collagen hydrolysate, passion fruit peel extract, Curcuma longaextract, Boswellia serrataextract, curcumin, pycnogenol and L-carnitine) demonstrated large (effect size >0.80) and clinically important effects for pain reduction at short term. Another six (undenatured type II collagen, avocado soybean unsaponifiables, methylsulfonylmethane, diacerein, glucosamine and chondroitin) revealed statistically significant improvements on pain, but were of unclear clinical importance. Only green-lipped mussel extract and undenatured type II collagen had clinically important effects on pain at medium term. No supplements were identified with clinically important effects on pain reduction at long term. Similar results were found for physical function. Chondroitin demonstrated statistically significant, but not clinically important structural improvement (effect size −0.30, –0.42 to −0.17). There were no differences between supplements and placebo for safety outcomes, except for diacerein. The Grading of Recommendations Assessment, Development and Evaluation suggested a wide range of quality evidence from very low to high.ConclusionsThe overall analysis including all trials showed that supplements provided moderate and clinically meaningful treatment effects on pain and function in patients with hand, hip or knee osteoarthritis at short term, although the quality of evidence was very low. Some supplements with a limited number of studies and participants suggested large treatment effects, while widely used supplements such as glucosamine and chondroitin were either ineffective or showed small and arguably clinically unimportant treatment effects. Supplements had no clinically important effects on pain and function at medium-term and long-term follow-ups.

Recent large-scale genetic sequencing efforts have identified rare coding variants in genes in the triglyceride-rich lipoprotein (TRL) clearance pathway that are protective against coronary heart disease (CHD), independently of LDL cholesterol (LDL-C) levels. Insight into the mechanisms of protection of these variants may facilitate the development of new therapies for lowering TRL levels. The gene APOC3 encodes apoC-III, a critical inhibitor of triglyceride (TG) lipolysis and remnant TRL clearance. Here we report a detailed interrogation of the mechanism of TRL lowering by the APOC3 Ala43Thr (A43T) variant, the only missense (rather than protein-truncating) variant in APOC3 reported to be TG lowering and protective against CHD. We found that both human APOC3 A43T heterozygotes and mice expressing human APOC3 A43T display markedly reduced circulating apoC-III levels. In mice, this reduction is due to impaired binding of A43T apoC-III to lipoproteins and accelerated renal catabolism of free apoC-III. Moreover, the reduced content of apoC-III in TRLs resulted in accelerated clearance of circulating TRLs. On the basis of this protective mechanism, we developed a monoclonal antibody targeting lipoprotein-bound human apoC-III that promotes circulating apoC-III clearance in mice expressing human APOC3 and enhances TRL catabolism in vivo. These data reveal the molecular mechanism by which a missense variant in APOC3 causes reduced circulating TG levels and, hence, protects from CHD. This protective mechanism has the potential to be exploited as a new therapeutic approach to reduce apoC-III levels and circulating TRL burden.

The purpose of this paper is to determine a class of neutral stochastic functional integro-differential system in real separable Hilbert spaces as well as the exponential stability results. The Rosenblatt process acts as the driving force behind the systems. Initially, the existence results for mild solutions of the stochastic system is investigated by using stochastic analysis, integro-differential theory, and fixed point theory. The analysis of the exponential stability of mild solutions to nonlinear neutral stochastic integro-differential systems driven by Rosenblatt process is the main objective of the investigation’s further stages. The system’s trajectory controllability is then examined using Gronwall’s inequality. An example is given to validate the results at the end. Our work extends the work of Chalishajar et al. (2010), Chalishajar and Chalishajar (2015), Chalishajar et al. (2023), Muslim and George (2019) and Durga et al. (2022) where the pth moment exponential stability has not discussed. Also, numerical simulation has not studied in Chalishajar et al. (2023), Muslim and George (2019) and Durga et al. (2022).

COVID-19 had a global impact, claiming many lives and disrupting healthcare systems even in many developed countries. Various mutations of the severe acute respiratory syndrome coronavirus-2, continue to be an impediment to early detection of this disease, which is vital for social well-being. Deep learning paradigm has been widely applied to investigate multimodal medical image data such as chest X-rays and CT scan images to aid in early detection and decision making about disease containment and treatment. Any method for reliable and accurate screening of COVID-19 infection would be beneficial for rapid detection as well as reducing direct virus exposure in healthcare professionals. Convolutional neural networks (CNN) have previously proven to be quite successful in the classification of medical images. A CNN is used in this study to suggest a deep learning classification method for detecting COVID-19 from chest X-ray images and CT scans. Samples from the Kaggle repository were collected to analyse model performance. Deep learning-based CNN models such as VGG-19, ResNet-50, Inception v3 and Xception models are optimized and compared by evaluating their accuracy after pre-processing the data. Because X-ray is a less expensive process than CT scan, chest X-ray images are considered to have a significant impact on COVID-19 screening. According to this work, chest X-rays outperform CT scans in terms of detection accuracy. The fine-tuned VGG-19 model detected COVID-19 with high accuracy—up to 94.17% for chest X-rays and 93% for CT scans. This work thereby concludes that VGG-19 was found to be the best suited model to detect COVID-19 and chest X-rays yield better accuracy than CT scans for the model.

There is currently no targeted therapy to treat NF1-mutant melanomas. In this study, we compared the genomic and transcriptomic signatures of NF1-mutant and NF1wild-type melanoma to reveal potential treatment targets for this subset of patients. Genomic alterations were verified using qPCR, and differentially expressed genes were independently validated using The Cancer Genome Atlas data and immunohistochemistry. Digital spatial profiling with multiplex immunohistochemistry and immunofluorescence were used to validate the signatures. The efficacy of combinational regimens driven by these signatures was tested through in vitro assays using low-passage cell lines. Pathogenic NF1mutations were identified in 27% of cases. NF1-mutant melanoma expressed higher proliferative markers MK167and CDC20than NF1wild-type (P = 0.008), which was independently validated both in The Cancer Genome Atlas dataset (P = 0.01, P = 0.03) and with immunohistochemistry (P = 0.013, P = 0.036), respectively. Digital spatial profiling analysis showed upregulation of LY6Ewithin the tumor cells (false discovery rate < 0.01, log2 fold change > 1), confirmed with multiplex immunofluorescence showing colocalization of LY6Ein melanoma cells. The combination of MAPK/extracellular signal‒regulated kinase kinase and CDC20coinhibition induced both cytotoxic and cytostatic effects, decreasing CDC20expression in multiple NF1-mutant cell lines. In conclusion, NF1-mutant melanoma is associated with a distinct genomic and transcriptomic profile. Our data support investigating CDC20inhibition with MAPK pathway inhibitors as a targeted regimen in this melanoma subtype.

There is a paucity of data examining disparities in influenza vaccination at the intersection of disability and race.

The Supplemental Nutrition Assistance Program (SNAP) is a federal public benefit providing food assistance to millions of Americans. However, it is typically administered by states, creating potential variation in accessibility and transparency of information about enrollment for people with disabilities.

The COVID-19 pandemic has exacerbated historical inequities for people with disabilities including barriers in accessing online information and healthcare appointment websites. These barriers were brought to the foreground during the vaccine rollout and registration process.

In this paper, the robust control problem of interacting nonlinear multi-input multi-output (MIMO) systems is proposed. The robustness against unknown process parameter variation is considered. Three algorithms based on the Sliding Mode Control (SMC) are proposed: SMC with conventional surface, SMC with PID surface and SMC with integral surface. The effectiveness of these algorithms are simulated and implemented on Two Conical Tank Interacting Level System (TCTILS) which exhibits dynamic non linearity and coupling dynamics. The SMC with conventional sliding surface provides robust control against parameter variation and excellent set point tracking compared to SMC with PID sliding surface and SMC with integral sliding surface.

Limited studies have indicated that Americans with vision loss are differentially impacted by COVID-19.

Pregnancy reprograms mammary epithelial cells (MECs) to control their responses to pregnancy hormone re-exposure and carcinoma progression. However, the influence of pregnancy on the mammary microenvironment is less clear. Here, we used single-cell RNA sequencing to profile the composition of epithelial and non-epithelial cells in mammary tissue from nulliparous and parous female mice. Our analysis indicates an expansion of γδ natural killer T-like immune cells (NKTs) following pregnancy and upregulation of immune signaling molecules in post-pregnancy MECs. We show that expansion of NKTs following pregnancy is due to elevated expression of the antigen-presenting molecule CD1d on MECs. Loss of CD1d expression on post-pregnancy MECs, or overall lack of activated NKTs, results in mammary oncogenesis. Collectively, our findings illustrate how pregnancy-induced changes modulate the communication between MECs and the immune microenvironment and establish a causal link between pregnancy, the immune microenvironment, and mammary oncogenesis.

A novel conceptual mechanism for cooling Giant magneto resistance (GMR) nanostructures using bismuth telluride (BixTey) thermoelectric caps is reported for first time. BixTey thin films and nanowires were electrodeposited from an aqueous electrolyte solution using a constant potential method. GMR layered structures were electrodeposited form a Co-rich electrolyte using a pulsed potential technique. Optimal deposition potentials were identified from polarization analysis. Thin film morphology was found to be strongly dependent on deposition potentials. With increased deposition potentials crystalline to polycrystalline transition and decreased Te concentration were observed from XRD and EDS analysis, respectively. A maximum Seebeck coefficient of -200uV/K was obtained at 345K for a thin film sample deposited at -150mV.

Hemolysis, inflammation and coagulopathy associated with sickle cell disease (SCD) can lead to pulmonary hypertension. More than 15% of adult patients with SCD are affected by pulmonary hypertension as measured by a tricuspid regurgitation velocity (TRV) ≥ 2.9 m/sec (Nouraie, M. et al., Validation of a composite vascular high-risk profile for adult patients with sickle cell disease. American Journal of Hematology, 94:E312-E314. 2019). Moreover, sickle cell disease patients with pulmonary hypertension have a much higher mortality risk than those without pulmonary hypertension. There is little knowledge on the proteomic profile of pulmonary hypertension in SCD. Our aim was to conduct a proof-of-concept study to explore targeted serum protein biomarkers that are differentially expressed in SCD patients with elevated tricuspid regurgitation velocities and explore their corresponding pathways.

Prior research has demonstrated that the needs of the disability community have not been met during public health emergencies. The COVID-19 pandemic has exacerbated existing inequities for many populations including people with disabilities, and data is needed to develop inclusive public health response policies.

To provide a summary of the translational gaps in musculoskeletal research as identified in the Mine the Gap workshop and propose possible solutions.

Autism is one of the developmental disorders which make major behavioral and communication changes in the individual and induce a major drawback in the walking pattern. The main aim of this study is to analyze and compare the stride patterns of an autistic patient and a healthy individual. With the help of the proposed device, the yaw, pitch and roll of the limbs can be easily measured and analyzed. These parameters will identify the lacking movement patterns and help the physiotherapists in improving the walking pattern of the autistic patients by adopting the correct approach of remedial actions/treatment. It can also be used by the people who have undergone hip replacements or knee replacements and have an abnormal gait pattern. This device is a simple accumulation of sensors and memory storage unit. Two gyroscope sensors have been used, one each for the knee and the ankle. These sensors are strapped onto the knee and ankle with the help of free-sized elastic bands. The data received by the sensors are stored in the storage device automatically and are evaluated in a specially designed Web application. However, the raw data from the gyroscope sensors have not been used directly and various filters have been used to remove the errors. The results have been compared between an autistic patient and a normal healthy subject and showed a higher degree of angle difference for the autistic patient than the normal individual.

HIV infection predisposes latent tuberculosis-infected (LTBI) subjects to active TB. This study is designed to determine whether HIV infection of LTBI subjects compromises the balanced Mycobacterium tuberculosis(Mtb)-specific T helper 17 (Th17) response of recognized importance in anti-TB immunity. Comparative analysis of Mtb- and cytomegalovirus (CMV)-specific CD4+T cell responses demonstrates a marked dampening of the Mtb-specific CD4+T cell effectors and polyfunctional cells while preserving CMV-specific response. Additionally, HIV skews the Mtb-specific Th17 response in chronic HIV-infected LTBI progressors, but not long-term non-progressors (LTNPs), with preservation of pro-inflammatory interferon (IFN)-γ+/interleukin-17+(IL-17+) and significant loss of anti-inflammatory IL-10+/IL-17+effectors that is restored by anti-retroviral therapy (ART). HIV-driven impairment of Mtb-specific response cannot be attributed to preferential infection as cell-associated HIV DNA and HIV RNA reveal equivalent viral burden in CD4+T cells from different antigen specificities. We therefore propose that beyond HIV-induced loss of Mtb-specific CD4+T cells, the associated dysregulation of Mtb-specific T cell homeostasis can potentially enhance the onset of TB in LTBI subjects.

Nutrient stress triggers transcriptional changes that limit Ca2+influx into mitochondria through the MCU.

Objective:To determine the prevalence of cognitive (memory or confusion) complaints in older adults with visual impairment (VI). Method:We assessed the relationship between VI (corrected visual acuity [VA] < 20/40) and self-reported confusion or problems with memory among participants aged 60 years to 85 years in the 1999-2006 cycles of National Health and Nutrition Examination Survey (n= 5,795). Prevalence estimates of cognitive complaints were calculated using Current Population Surveys. Results:Memory/confusion complaints were reported in 22% of the VI group and 11% of the no VI group (p< .001). In individuals aged ≥ 80 years, 30% of those with VI reported cognitive complaints, as compared with 19% with no VI (p= .003). In fully adjusted models, individuals with VI were more likely (OR = 1.3, p= .049) to report cognitive complaints as compared with those without VI. Conclusion:Subjective reports of memory or confusion are highly prevalent in older individuals with VI.

Osteopenia and Osteoporosis are major bone metabolic diseases among people especially in women aged above 50 years old. The bone related problems pose an increasing economic demand in our healthcare system. Study and research in bone and tissues has grown exponentially over the last years. The knowledge of the mechanical properties of bone will enhance the understanding of the effect of bone related fractures. In people affected with low bone mineral density, the fractures are common in the vertebral bodies of the spine. In this study, Computed tomography images of human lumbar spine is segmented in the required region (L3 to L5). The three dimensional model of the segmented image was used to develop finite element model. Further, model of the human lumbar spine L3 to L5 was validated with literature. This validated model of human lumbar spine is modified to osteopenia and osteoporosis conditions with different mechanical properties and range of motion is analyzed. The analysis and the comparison is made with that of normal human lumbar spine. The results produced in this study can be used in studies related to vertebroplasty and kyphoplasty.

The C4-C6 region of the cervical spine is a common area of injury in the spinal column. Most of the injuries are caused due to accidents, sports etc. These injuries with increase in age can lead to slight, moderate and severe disc degeneration. As technology has advanced over the years, biomechanical finite element models are used instead of cadavers to study effects of progressive degeneration on the stress distribution. This study was conducted to develop a three dimensional finite element model of the C4-C6 human cervical spine structure using computed tomography scans and was validated against experimental data published earlier. The model was then used to produce progressive disc degeneration at the C4-C6 region by varying the material properties. Slight degeneration and moderate degeneration is obtained by modifying the material properties of nucleus pulposus and annulus fibrosus respectively. Severe degeneration was achieved by taking the material properties for maximum degeneration. The degenerated models were subjected to flexion, extension and lateral bending and the stress distribution on the anterior and posterior region were determined and compared with the intact model. Based on this study, the anterior region showed more increase in stress as compared to the posterior region with progressive degeneration.

In the present paper the work is done based on the experimentation of biodiesel blends using diesel and waste cooking oil with and without adding cow urine as additive in various proportions. The properties such as the flash point, fire point, kinematic viscosity and the calorific values of the blends with and without additive are determined. Then all the biodiesel blends are used as fuel separately in the diesel engine. The emission characteristics and the performance parameters are evaluated. From the results, it was observed that the blends with additive as shown slight improvement in performance but significant reduction in emission. Fuel consumption was more for the higher percentage blends with respect to increasing brake power. Brake thermal efficiency was higher in 50% for the both the blends with and without additive. It can be concluded stating that the same procedure can be followed with various blend ratios in order to differentiate and find the optimum blend as an alternative fuel.

Background: Children with acute lymphoblastic leukemia (ALL) who relapse are more resistant to chemotherapy. We have previously identified a unique gene expression signature associated with relapsed leukemic blasts and showed that relapse samples have higher level of CpG methylation compared to diagnosis. We also demonstrated that treatment with DNMT inhibitor, decitabine, alone or in combination with the HDAC inhibitor, vorinostat restored blast chemosensitivity in vitro. These observations led to the hypothesis that global methylation status is a key regulator of drug resistance.

Maria: Novartis: Equity Ownership. Levine:Qiagen: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy. Cao:Novartis: Equity Ownership; BMS: Equity Ownership.

AbstractThe selection intensity indices were computed based on the demographic information pertaining to fertility and mortality among the Paki, an endogamous caste population of Andhra Pradesh. In the present population, the selection is manifested mainly through differential fertility rather than mortality. This situation may be due to changing socio-economic condition of these people.