Evaluating the Efficacy of Cervical Tactile Ultrasound Technique as a Predictive Tool for Spontaneous Preterm Birth

Background: Premature cervical softening and shortening may be considered an early mechanical failure that predispose to preterm birth. Purpose: This study aims to explore the applicability of an innovative cervical tactile ultrasound approach for predicting spontaneous preterm birth (sPTB). Materials and Methods: Eligible participants were women with low-risk singleton pregnancies in their second trimester, enrolled in this prospective observational study. A Cervix Monitor (CM) device was designed with a vaginal probe comprising four tactile sensors and a single ultrasound transducer operating at 5 MHz. The probe enabled the application of controllable pressure to the external cervical surface, facilitating the acquisition of stress-strain data from both anterior and posterior cervical sectors. Gestational age at delivery was recorded and compared against cervical elasticity. Results: CM examination data were analyzed for 127 women at 240/7 - 286/7 gestational weeks. sPTB was observed in 6.3% of the cases. The preterm group exhibited a lower average cervical stress-to-strain ratio (elasticity) of 0.70 ± 0.26 kPa/mm compared to the term group’s 1.63 ± 0.65 kPa/mm with a p-value of 1.1 × 10−4. Diagnostic accuracy for predicting spontaneous preterm birth based solely on cervical elasticity data was found to be 95.0% (95% CI, 88.5 - 100.0). Conclusion: These findings suggest that measuring cervical elasticity with the designed tactile ultrasound probe has the potential to predict spontaneous preterm birth in a cost-effective manner.

Remodeling neuroscience education in medical student training:how early exposure and mentorship are promoting student interest in neurology and neurosurgery

Exposure to clinical neurology is an essential aspect of a young clinician＇s training. Neuroscience forms the cornerstone of a wide variety of clinical pathologies and many believe it is currently under represented in medical education. This phenomenon persists as the rapidly aging population places an increasing burden on neuromedical specialists. This demographic change, compounded by the expected 19% shortage in clinical neurologists by 2025, makes it imperative to reexamine specific aspects of neuro- medical education （Dall et al., 2013）. These aspects include the timing of pre-clinical neuroscience education, the presence of faculty supported interest groups, the existence of formal mentorship programs, and the availability of neurology and neurosurgical clerkships to 3rd year medical students. Given the increasing importance of neuromedi- cal training, several recent studies have examined the state of neurology training in modern medical education and its impact on medical graduates.

Hepatic pseudotumor associated with Strongyloides infection:A case report

BACKGROUND Strongyloides sterocoralis is a parasitic infection caused by a roundworm that is transmitted through soil contaminated with larvae.It can infrequently cause hepatic abscesses in immunocompromised patients and is rarely reported to form hepatic lesions in immunocompetent hosts.CASE SUMMARY We present a case study of a 45-year-old female who presented with right upper quadrant abdominal pain and constitutional symptoms for several weeks.Crosssectional imaging identified several malignant-appearing liver masses.Further investigation,including serological testing and histopathologic examination,revealed the presence of serum Strongyloides antibodies and hepatic granulomas with extensive necrosis.Following treatment with ivermectin for 2 wk,there was complete resolution of the liver lesions and associated symptoms.CONCLUSION This case highlights the importance of considering parasitic infections,such as Strongyloides,in the differential diagnosis of hepatic masses.Early recognition and appropriate treatment can lead to a favorable outcome and prevent unnecessary invasive procedures.Increased awareness among clinicians is crucial to ensure the timely diagnosis and management of such cases.

Acute kidney injury and hepatorenal syndrome in cirrhosis

Acute kidney injury(AKI)in cirrhosis,including hepatorenal syndrome(HRS),is a common and serious complication in cirrhotic patients,leading to significant morbidity and mortality.AKI is separated into two categories,non-HRS AKI and HRS-AKI.The most recent definition and diagnostic criteria of AKI in cirrhosis and HRS have helped diagnose and prognosticate the disease.The pathophysiology behind non-HRS-AKI and HRS is more complicated than once theorized and involves more processes than just splanchnic vasodilation.The common biomarkers clinicians use to assess kidney injury have significant limitations in cirrhosis patients;novel biomarkers being studied have shown promise but require further studies in clinical settings and animal models.The overall management of non-HRS AKI and HRS-AKI requires a systematic approach.Although pharmacological treatments have shown mortality benefit,the ideal HRS treatment option is liver transplantation with or without simultaneous kidney transplantation.Further research is required to optimize pharmacologic and nonpharmacologic approaches to treatment.This article reviews the current guidelines and recommendations of AKI in cirrhosis.

Status of precision medicine approaches to traumatic brain injury

Traumatic brain injury(TBI)is a serious condition in which trauma to the head causes damage to the brain,leading to a disruption in brain function.This is a significant health issue worldwide,with around 69 million people suffering from TBI each year.Immediately following the trauma,damage occurs in the acute phase of injury that leads to the primary outcomes of the TBI.In the hours-to-days that follow,secondary damage can also occur,leading to chronic outcomes.TBIs can range in severity from mild to severe,and can be complicated by the fact that some individuals sustain multiple TBIs,a risk factor for worse long-term outcomes.Although our knowledge about the pathophysiology of TBI has increased in recent years,unfortunately this has not been translated into effective clinical therapies.The U.S.Food and Drug Administration has yet to approve any drugs for the treatment of TBI;current clinical treatment guidelines merely offer supportive care.Outcomes between individuals greatly vary,which makes the treatment for TBI so challenging.A blow of similar force can have only mild,primary outcomes in one individual and yet cause severe,chronic outcomes in another.One of the reasons that have been proposed for this differential response to TBI is the underlying genetic differences across the population.Due to this,many researchers have begun to investigate the possibility of using precision medicine techniques to address TBI treatment.In this review,we will discuss the research detailing the identification of genetic risk factors for worse outcomes after TBI,and the work investigating personalized treatments for these higher-risk individuals.We highlight the need for further research into the identification of higher-risk individuals and the development of personalized therapies for TBI.

Addition of simvastatin to carvedilol non responders: A new pharmacological therapy for treatment of portal hypertension

AIMTo determine whether addition of simvastatin could be an important pharmacological rescue therapy for carvedilol non-responders. METHODSOne hundred and two consecutive patients of cirrhosis of liver with significant portal hypertension were included. Hepatic venous pressure gradient (HVPG) was measured at the base line and after proper optimization of dose; chronic response was assessed at 3 mo. Carvedilol non-responders were given simvastatin 20 mg per day (increased to 40 mg per day at day 15). Carvedilol plus simvastatin was continued for 1 mo and hemodynamic response was again measured at 1 mo. RESULTSA total of 102 patients with mean age of 58.3 ± 6.6 years were included. Mean baseline HVPG was 16.75 ± 2.12 mmHg and after optimization of dose and reassessment of HVPG at 3 mo, mean reduction of HVPG from baseline was 5.5 ± 1.7 mmHg and 2.8 ± 1.6 mmHg among responders and non-responders respectively (P CONCLUSIONAddition of simvastatin to carvedilol non-responders may prove to be an excellent rescue therapy in patients with portal hypertension.

Endovascular treatment of pulmonary embolism: Selective review of available techniques

Acute pulmonary embolism(PE) is the third most common cause of death in hospitalized patients. The development of sophisticated diagnostic and therapeutic modalities for PE, including endovascular therapy, affords a certain level of complexity to the treatment of patients with this important clinical entity. Furthermore, the lack of level I evidence for the safety and effectiveness of catheter directed therapy brings controversy to a promising treatment approach. In this review paper, we discuss the pathophysiology and clinical presentation of PE, review the medical and surgical treatment of the condition, and describe in detail the tools that are available for the endovascular therapy of PE, including mechanical thrombectomy, suction thrombectomy, and fibrinolytic therapy. We also review the literature available to date on these methods, and describe the function of the Pulmonary Embolism Response Team.

Microglial voltage-gated proton channel Hv1 in spinal cord injury

After spinal cord injury,microglia as the first responders to the lesion display both beneficial and detrimental characteristics.Activated microglia phagocyte and eliminate cell debris,release cytokines to recruit peripheral immune cells to the injury site.Excessively activated microglia can aggravate the secondary damage by producing extravagant reactive oxygen species and pro-inflammatory cytokines.Recent studies demonstrated that the voltage-gated proton channel Hv1 is selectively expressed in microglia and regulates microglial activation upon injury.In mouse models of spinal cord injury,Hv1 deficiency ameliorates microglia activation,resulting in alleviated production of reactive oxygen species and pro-inflammatory cytokines.The reduced secondary damage subsequently decreases neuronal loss and correlates with improved locomotor recovery.This review provides a brief historical perspective of advances in investigating voltage-gated proton channel Hv1 and home in on microglial Hv1.We discuss recent studies on the roles of Hv1 activation in pathophysiological activities of microglia,such as production of NOX-dependent reactive oxygen species,microglia polarization,and tissue acidosis,particularly in the context of spinal cord injury.Further,we highlight the rationale for targeting Hv1 for the treatment of spinal cord injury and related disorders.

Androgen synthesis inhibitors in the treatment of castration-resistant prostate cancer

Suppression of gonadal testosterone synthesis represents the standard first line therapy for treatment of metastatic prostate cancer. However, in the majority of patients who develop castration-resistant prostate cancer （CRPC）, it is possible to detect persistent activation of the androgen receptor （AR） through androgens produced in the adrenal gland or within the tumor itself. Abiraterone acetate was developed as an irreversible inhibitor of the dual functional cytochrome P450 enzyme CYP17 with activity as a 17（^-hydroxylase and 17,20-1yase. CYP17 is necessary for production of nongonadal androgens from cholesterol. Regulatory approval of abiraterone in 2011, based on a phase III trial showing a significant improvement in overall survival （OS） with abiraterone and prednisone versus prednisone, represented proof of principle that targeting AR is essential for improving outcomes in men with CRPC. Inhibition of 17α-hydroxylase by abiraterone results in accumulation of upstream mineralocorticoids due to loss of cortisol-mediated suppression of pituitary adrenocorticotropic hormone （ACTH）, providing a rationale for development of CYP17 inhibitors with increased specificity for 17,20-1yase （orteronel, galeterone and VT-464） that can potentially be administered without exogenous corticosteroids. In this article, we review the development of abiraterone and other CYP17 inhibitors; recent studies with abiraterone that inform our understanding of clinical parameters such as drug effects on quality-of-life, potential early predictors of response, and optimal sequencing of abiraterone with respect to other agents; and results of translational studies providing insights into resistance mechanisms to CYP17 inhibitors leading to clinical trials with drug combinations designed to prolong abiraterone benefit or restore abiraterone activity.

Highly active antiretroviral therapy dysregulates proliferation and differentiation of human pre-adipocytes

AIM To investigate the mechanism(s) by which potential effects of multi-drug highly-active antiretroviral therapy contributes to lipodystrophy syndrome. METHODS Preadipocytes from healthy donors were assessed for proliferation and differentiation in the presence of nucleoside reverse transcriptase inhibitors(NRTIs), nonnucleoside reverse transcriptase inhibitors(NNRTIs), and protease inhibitors(PIs) individually and in combination. Effects on proliferation were assessed with a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide assay and effects on differentiation were assessed from glycerol-3-phosphate dehydrogenase(GPDH) activity and quantitation of Oil Red O staining for intracellular lipid. Data were analyzed with a randomized block ANOVA with post-hoc Fisher's Least Significant Difference test. RESULTS Preadipocyte proliferation was inhibited by a combination of NNRTI + NRTI(14% at 48 h, P < 0.001) and PI + NRTI(19% at 48 h, P < 0.001) with additional suppression when ritonavir(RTV) was added(26% at 48 h). The drug combination of atazanavir(ATV) + RTV + emtricitabine(FTC) + tenofovir(TDF) had the greatest inhibitory effect on proliferation at 48 h. Preadipocyte differentiation was most significantly reduced by the efavirenz + FTC + TDF assessed either by GPDH activity(64%) or lipid accumulation(39%), P < 0.001. Combining NRTIs with a PI(ATV + FTC + TDF) significantly suppressed differentiation(GPDH activity reduced 29%, lipid accumulation reduced by 19%, P < 0.01). This effect was slightly greater when a boosting amount of RTV was added(ATV + FTC + TDF + RTV, P < 0.001). CONCLUSION Although combination antiretroviral therapy is clinically more efficacious than single drug regimens, it also has a much greater inhibitory effect on preadipocyte proliferation and differentiation.

Risk scoring model for prediction of non-home discharge after transcatheter aortic valve replacement

Background Patients undergoing transcatheter aortic valve replacement(TAVR) are likely to be discharged to a location other than home. We aimed to determine the association between preoperative risk factors and non-home discharge after TAVR. Methods Patients discharged alive after TAVR at three centers were identified from a prospectively maintained database randomly divided into 80% derivation and 20% validation cohorts. Logistic regression models were fit to identify preoperative factors associated with non-home discharge in the derivation cohort. Multivariable models were developed and a nomogram based risk-scoring system was developed for use in preoperative counseling. Results Between June 2012 and December 2018, a total of 1,163 patients had TAVR at three centers. Thirty-seven patients who died before discharge were excluded. Of the remaining 1,126 patients(97%) who were discharged alive, the incidence of non-home discharge was 25.6%(n = 289). The patient population was randomly divided into the 80%(n = 900) derivation cohort and 20%(n = 226) validation cohort. Mean ± SD age of the study population was 83 ± 8 years. In multivariable analysis, factors that were significantly associated with non-home discharge were extreme age, female sex, higher STS scores, use of general anesthesia, elective procedures, chronic liver disease, non-transfemoral approach and postoperative complications. The unbiased estimate of the C-index was 0.81 and the model had excellent calibration. Conclusions One out of every four patients undergoing TAVR is discharged to a location other than home. Identification of preoperative factors associated with non-home discharge can assist patient counseling and postoperative disposition planning.

Vein of Galen malformation in a neonate:A case report and review of endovascular management

Vein of Galen malformation(VOGM) is a rare congenital vascular malformation caused by the maldevelopment of its embryonic precursor,the median prosencephalic vein of Markowski.VOGM results in neonatal morbidity and mortality,and premature delivery does not improve the outcome.We report a term female neonate in whom a vein of Galen malformation was diagnosed prenatally at 37 wk of gestation during a growth ultrasound and confirmed by fetal magnetic resonance imaging.Signs of cardiac decompensation were evident in the fetus.Multiple interventional radiology embolizations of the feeding vessels were performed successfully on days 7,10,12,14 and 19.A review of the literature on the endovascular management of neonates with these malformations is presented herein.

Posterior reversible encephalopathy syndrome in alcoholic hepatitis:Hepatic encephalopathy a common theme

Posterior reversible encephalopathy syndrome(PRES) is a neuro-radiologic diagnosis that has become more widely recognized and reported over the past few decades. As such, there are a number of known risk factors that contribute to the development of this syndrome, including volatile blood pressures, renal failure, cytotoxic drugs, autoimmune disorders, pre-eclampsia, and eclampsia. This report documents the first reported case of PRES in a patient with severe alcoholic hepatitis with hepatic encephalopathy and delves into a molecular pathophysiology of the syndrome.

COVID-19 status quo:Emphasis on gastrointestinal and liver manifestations

The coronavirus disease 2019(COVID-19)has caused one of the worst public health crises in modern history.Even though severe acute respiratory syndrome coronavirus 2 primarily affects the respiratory tract,gastrointestinal manifestations are well described in literature.This review will discuss the epidemiology,virology,manifestations,immunosuppressant states,and lessons learned from COVID-19.Observations:At the time of writing,COVID-19 had infected more than 111 million people and caused over 2.5 million deaths worldwide.Multiple medical comorbidities including obesity,pre-existing liver condition and the use of proton pump inhibitor have been described as risk factor for severe COVID-19.COVID-19 most frequently causes diarrhea(12.4%),nausea/vomiting(9%)and elevation in liver enzymes(15%-20%).The current data does not suggest that patients on immunomodulators have a significantly increased risk of mortality from COVID-19.The current guidelines from American Gastroenterological Association and American Association for the Study of Liver Diseases do not recommend pre-emptive changes in patients on immunosuppression if the patients have not been infected with COVID-19.Conclusions and relevance:The COVID-19 pandemic has prompted a change in structure and shape of gastroenterology departmental activities.Endoscopy should be performed only when necessary and with strict protective measures.Online consultations in the form of telehealth services and home drug deliveries have revolutionized the field.

Gastrointestinal bleeding in a patient with a continuous-flow biventricular assist device

The association between continuous-flow left ventricular assist devices(CF-LVADs)and gastrointestinal(GI)bleeding from angiodysplasia is well recognized.However,the association between continuous-flow biventricular assist devices(CF-BIVADs)and bleeding angiodysplasia is less understood.We report a case of GI bleeding from a patient with a CF-BIVAD.The location of GI bleeding was identified by nuclear red blood cell bleeding scan.The vascular malformation leading to the bleed was identified and localized on angiography and then by pathology.The intensity of bleeding,reflected by number of units of packed red blood cells needed for normalization of hemoglobin,as well as the time to onset of bleeding after transplantation,are similar to that seen in the literature for CF-LVADs and pulsatile BIVADs.While angiography only detected a dilated late draining vein,pathology demonstrated the presence of both arterial and venous dilation in the submucosa,vascular abnormalities characteristic of a late arteriovenous malformation.

Understanding axon guidance: attraction, repulsion, and statistical physics

Understanding axon guidance is important for developing therapies to restore neuronal connections damaged by injury or disease. Axons migrate in response to extraceUular guidance molecules that induce or inhibit axon outgrowth activity within the axon. The direction of guidance is determined by the attractive and repulsive responses that the axon has to the guidance cues. In a deterministic model of guidance, the direction of guidance can be precisely determined if the attractive and repulsive effect that each cue has on the axon is known. But what if there are numerous attractive and repulsive responses induced by multiple guidance cues, and the direction of the attractive and repulsive events fluctuates？ If the effect that each attractive and repulsive event has on guidance becomes too complex to measure then understand- ing how each molecular cue influences the guidance decision becomes impossible.

Augmented anastomotic urethroplasty with buccal mucosa for post penile fracture urethral injury long segment bulbar urethral stricture review

Dear editor,The national incidence of penile fracture in the United States is estimated as 1.02 per 100000 males[1].Nine to twenty percent of these injuries result in a concomitant urethral injury[2,3].Barros et al.[4]reported that 85 out of 888 penile fractures men with penile fractures had concomitant urethral injuries[4].Among those with both a penile fracture and urethral injury,only two cases of urethral stricture were reported.Furthermore,only three percent of urethral strictures resulted from penile fractures[5].These data highlight the relatively low incidence of urethral stricture in patients with penile fracture and concomitant urethral injury.

Offshore Training in Navy Personnel Is Associated with Uninvestigated Dyspepsia

To investigate the known and new factors associated with uninvestigated dyspepsia （UD）, we surveyed 8600 Chinese navy personnel with offshore training shorter than 1 month or longer than 9 months per year. All respondents were required to complete a questionnaire covering demographics, the Chinese version of the Rome Ⅲ survey, eating habits, life styles, and medical and family history. The response rate was 94.3% （8106/8600） with 4899 respondents qualified for analysis, including 1046 with offshore training and 3853 with onshore training. The prevalence of UD was higher in the offshore group than in the onshore group （12.6% vs. 6.9%, P〈0.001）, with a general prevalence of 8.1%. The subjects with offshore training were more likely to suffer from UD and postprandial distress syndrome （OR= 1.955 95% CI 1.568-2.439, P〈0.001 and OR=1.789, 95% CI 1.403-2.303, P〈0.001, respectively）. The mul- tivariate logistic regression analysis showed UD was associated with offshore training （OR=1.580, 95% CI 1.179-2.118, P=-0.002）, family history （OR=1.765, 95% CI 1.186-2.626, P=0.005） and smoking （OR=1.270, 95% CI 1.084-1.488, P=0.003）, but not with alcohol drinking. The association between dysentery history and UD was undetermined/borderline （P=0.056-0.069）. In conclusion, we identified offshore training as a new factor associated with UD, and also confirmed 2 known associated factors, family history and smoking.

Perceptions of Climate Change, Sea Level Rise, and Possible Consequences Relate Mainly to Self-Valuation of Science Knowledge

This study examines perceptions of climate change and sea level rise in New Jersey residents in 2012 and 2014. Different surveys have shown declines in interest and concern about climate change and sea level rise. Climate change and increasing temperatures have an anthropogenic cause, which relates to energy use, making it important to examine whether people believe that it is occurring. In late 2012 New Jersey experienced Super storm Sandy, one of the worst hurricanes in its history, followed by public discussion and media coverage of stronger more frequent storms due to climate change. Using structured interviews, we tested the null hypotheses that there were no differences in perceptions of 1260 interviewees as a function of year of the survey, age, gender, years of education, and self-evaluation of science knowledge (on a scale of 1 to 5). In 2012 460 of 639 (72%) rated “global warming occurring” as “certain” (#4) or “very certain” (#5) compared with 453 of 621 (73%) in 2014. For “due to human activities” the numbers of “certain” or “very certain” were 71% in 2012, and 67% in 2014 and for sea level rise the numbers were 64% and 70%. There were some inconsistent between-year differences with higher ratings in 2012 for 3 outcomes and higher ratings in 2014 for 5 outcomes. However, for 25 questions relative to climate change, sea level rise, and the personal and ecological effects of sea level rise, self-evaluation of science knowledge, independent of years of education, was the factor that entered 23 of the models, accounting for the most variability in ratings. People who believed they had a “high knowledge” (#4) or “very high knowledge” (#5) of science rated all issues as more important than did those people who rated their own scientific knowledge as average or below average.

fRAP 2.0:a community engagement method applied to cervical cancer disparities among Hispanic women

focused Rapid Assessment Process(fRAP)2.0 is a community engagement approach combining geospatial mapping with rapid qualitative assessment in cyclical fashion within communities to capture multifactorial and multilevel features impacting primary care problems.fRAP 2.0 offers primary care researchers a methodology framework for exploring complex community features that impact primary healthcare delivery and outcomes.The fRAP 2.0 study design expands the fRAP from a sequential design to a cyclical process of geospatial mapping and rapid qualitative assessment in search of modifiable contextual factors.Research participants are stakeholders from various socioecological levels whose perspectives inform study outcomes that they may use to then become the agents of change for the very problems they helped explore.Here,we present a proof-of-concept study for fRAP 2.0 examining disparities in cervical cancer mortality rates among Hispanic women in Texas.The primary outcomes of interest are features at the community level,medical health system level and regional government policy levels that offer opportunities for collaborative interventions to improve cervical cancer outcomes.In this study,geospatial mapping of county and ZIP code-level variables impacting postdiagnosis cervical cancer care at community,medical and policy levels were created using publicly available data and then overlaid with maps created with Texas Cancer Registry data for cervical cancer cases in three of the largest population counties.Geographically disparate areas were then qualitatively explored using participant observation and ethnographic field work,alongside 39 key informant interviews.Roundtable discussion groups and stakeholder engagement existed at every phase of the study.Applying the fRAP 2.0 method,we created an action-oriented roadmap of next steps to improve cervical cancer care disparities in the three Texas counties with emphasis on the high disparity county.We identified local change targets for advocacy and the results helped convene a stakeholder group that continues to actively create on-the-ground change in the high-disparity county to improve cervical cancer outcomes for Hispanic women.