Miracle-dz/UniFAR-FTUs huggingface dataset:
Preventing Obstetric Fistulas in Low-Resource Countries: Insights From a Haddon Matrix

&NA; An obstetric fistula is classically regarded as an “accident of childbirth” in which prolonged obstructed labor leads to destruction of the vesicovaginal/rectovaginal septum with consequent loss of urinary and/or fecal control. Obstetric fistula is highly stigmatizing and afflicted women often become social outcasts. Although obstetric fistula has been eliminated from advanced industrialized nations, it remains a major public health problem in the world's poorest countries. Several million cases of obstetric fistula are currently thought to exist in sub-Saharan Africa and south Asia. Although techniques for the surgical repair of such injuries are well known, it is less clear which strategies effectively prevent fistulas, largely because of the complex interactions among medical, social, economic, and environmental factors present in those countries where fistulas are prevalent. This article uses the Haddon matrix, a standard tool for injury analysis, to examine the factors influencing obstetric fistula formation in low-resource countries. Construction of a Haddon matrix provides a “wide angle” overview of this tragic clinical problem. The resulting analysis suggests that the most effective short-term strategies for obstetric fistula prevention will involve enhanced surveillance of labor, improved access to emergency obstetric services (particularly cesarean delivery), competent medical care for women both during and after obstructed labor, and the development of specialist fistula centers to treat injured women where fistula prevalence is high. The long-term strategies to eradicate obstetric fistula must include universal access to emergency obstetric care, improved access to family planning services, increased education for girls and women, community economic development, and enhanced gender equity. Successful eradication of the obstetric fistula will require the mobilization of sufficient political will at both the international and individual country levels to ensure that adequate resources are devoted to this problem and that maternal health becomes a high priority on national political agendas. Target Audience: Obstetricians & Gynecologists and Family Physicians Learning Objectives: After participating in this CME activity, physicians should be better able to apply the Haddon matrix, a tool commonly used for injury analysis, to the field of obstetrics and gynecology; analyze the problem of obstructed labor and obstetric fistula formation in low-resource countries using the Haddon matrix, and implement possible strategies for the prevention of obstetric fistulas and the mitigation of harm in cases of obstructed labor that arise from the use of the Haddon matrix.
Discovery of HLA‐B*480102 in Taiwanese

Human leucocyte antigen (HLA)‐B48, an antigen within 7C CREG (cross‐reacting group) ( Steiner et al., 2001 ) that cross‐reacts frequently with HLA‐B40 (i.e. HLA‐B60 and ‐B61) group of antibodies serologically, can be found in Alaskan Natives ( Leffell et al., 2002 ), Amerindians ( Martinez‐Naves et al., 1997 ), African Americans, Caucasians, and Oriental ethnicities ( Mori et al., 1997 ; Schipper et al., 1997 ; Cao et al., 2001 ; Middleton et al., 2004 ; Hong et al., 2005 ; Itoh et al., 2005 ; Lee et al., 2005 ; Ogata et al., 2007 ). Sequencing investigations demonstrated that the common allele encoding the B48 antigen is B*4801 ( Belich et al., 1992 ). To date, there are at least 16 WHO recognized B*48 alleles according to the most recent report from the WHO nomenclature committee ( Marsh et al., 2005 ). Here we report a newly discovered allele B*480102, a variant of B*4801, detected in a 55‐year‐old Taiwanese patient of Minan origin (southern China).
A Cyclic Pain: The Pathophysiology and Treatment of Menstrual Migraine

Catamenial migraine is a headache disorder occurring in reproductive-aged women relevant to menstrual cycles. Catamenial migraine is defined as attacks of migraine that occurs regularly in at least 2 of 3 consecutive menstrual cycles and occurs exclusively on day 1 to 2 of menstruation, but may range from 2 days before (defined as −2) to 3 days after (defined as +3 with the first day of menstruation as day +1). There are 2 subtypes: the pure menstrual migraine and menstrually related migraine. In pure menstrual migraine, there are no aura and no migraine occurring during any other time of the menstrual cycle. In contrast, menstrually related migraine also occurs in 2 of 3 consecutive menstrual cycles, mostly on days 1 and 2 of menstruation, but it may occur outside the menstrual cycle. Catamenial migraine significantly interferes with the quality of life and causes functional disability in most sufferers. The fluctuation of estrogen levels is believed to play a role in the pathogenesis of catamenial migraine. In this review, we discuss estrogen and its direct and indirect pathophysiologic roles in menstrual-related migraine headaches and the available treatment for women. Target Audience: Obstetricians and gynecologists, family physicians Learning Objectives: After completing this CME activity, physicians should be better able to discuss the pathophysiology of catamenial migraine, identify the risk factors for catamenial migraine among women, and list the prophylactic and abortive treatments for migraines.
Should hepatic dysplastic nodules and regenerative nodules be regarded as premalignant lesions and treated?

The American Association for the Study of Liver Diseases (AASLD) practice guidelines on management of hepatocellular carcinoma (HCC) was last updated in 2011; another update is anticipated soon. For high-grade dysplastic nodules (HGDNs), lowgrade dysplastic nodules (LGDNs), or large regenerative nodules (LRNs), it suggests “enhanced follow-up. ” No treatment would be provided until the diagnosis of HCC established during the follow-up. However, is follow-up always the best choice? Perhaps we can attempt to compare this to colorectal adenoma by focusing on their clinical behavior and malignant potential. In the National Comprehensive Cancer Network (NCCN) guideline, adenomatous polyps are accepted precursors to colorectal cancer (CRC) and removed to prevent cancer. A recent cohort study estimated that the average annual transition rate from advanced adenoma to CRC in men was 3.1%, so the 5-year-transition rate was around 15%. In HCC, several studies have revealed a relatively high transition rate of hepatic nodular lesions to HCC. In 154 patients with chronic hepatitis and cirrhosis, Kobayashi et al. reported the annual transition rate of 20% for patients with HGDN and 10% for patients with LGDN. The 5-year cumulative transition rate from HGDN and LGDN was 80.8% and 30.2%, respectively. Even regenerative nodules without dysplasia evolved into HCC in 12.4%. More recently, Sato et al. studied 68 LRNs and 20 dysplastic nodules (DNs) from 1,500 consecutive nodular lesions; the 50-month transition rate was 13.6% in LRNs and 40% in DNs. Earlier studies support these findings. Thus, DNs, especially HGDNs, have the high potential of malignant transition, and LRNs in patients with chronic hepatitis and cirrhosis can be considered as pre-HCC lesion. In AASLD guidelines, the continuum between HGDN and early HCC obscures the diagnosis, whereas the smaller lesions would be more likely to receive curative treatment. Thus, we further raise the enquiry of whether LRNs and DNs should undergo active treatment, perhaps with minimally invasive ablation therapies. Preventing the transition to HCC by actively treating DNs and LRNs, such as removing colonic adenomas, may not only improve overall outcome, but also potentially decrease the need for liver transplantation in patients who can live with wellcompensated cirrhosis. Certainly, this provocative concept would need to be studied in a prospective, randomized controlled trial with long-term follow-up.
Destructive cellular paths underlying familial and sporadic Parkinson disease converge on mitophagy

ABSTRACT The knowledge gap separating the molecular and cellular underpinnings of Parkinson disease (PD) and its pathology hinders treatment innovation. Adding to this difficulty is the lack of a reliable biomarker for PD. Our previous studies identify a link of 2 PD proteins, PINK1/PRKN Parkin to a mitochondrial motor adaptor RHOT1/Miro-1, which mediates mitochondrial motility and mitophagy. Here we review our recent paper showing that a third PD protein, LRRK2, also targets RHOT1 and regulates mitophagy, and pathogenic LRRK2 disrupts this function. Notably, we discover impairments in RHOT1 and mitophagy in sporadic PD patients with no known genetic backgrounds, pointing to RHOT1-mediated mitophagy as a convergent pathway in PD. This novelty opens new doors in PD research toward RHOT1-based therapy and biomarker development.
BNIP3L/NIX-dependent mitophagy regulates cell differentiation via metabolic reprogramming

ABSTRACT Macroautophagy/autophagy is the process by which cellular components are degraded and recycled within the lysosome. These components include mitochondria, the selective degradation of which is known as mitophagy. Mitochondria are dynamic organelles that constantly adapt their morphology, function, and number to accommodate the metabolic needs of the cell. Extensive metabolic reconfiguration occurs during cell differentiation, when mitochondrial activity increases in most cell types. However, our data demonstrate that during physiologic retinal ganglion cell (RGC) development, mitophagy-dependent metabolic reprogramming toward glycolysis regulates numbers of RGCs, which are the first neurons to differentiate in the retina and whose axons form the optic nerve. We show that during retinal development tissue hypoxia triggers HIF1A/HIF-1 stabilization, resulting in increased expression of the mitophagy receptor BNIP3L/NIX. BNIP3L-dependent mitophagy results in a metabolic shift toward glycolysis essential for RGC neurogenesis. Moreover, we demonstrate that BNIP3L-dependent mitophagy also regulates the polarization of proinflammatory/M1 macrophages, which undergo glycolysis-dependent differentiation during the inflammatory response. Our results uncover a new link between hypoxia, mitophagy, and metabolic reprogramming in the differentiation of several cell types in vivo. These findings may have important implications for neurodegenerative, metabolic and other diseases in which mitochondrial dysfunction and metabolic alterations play a prominent role.
BNIP3L/NIX-mediated mitophagy protects against ischemic brain injury independent of PARK2

ABSTRACT Cerebral ischemia induces massive mitochondrial damage. These damaged mitochondria are cleared, thus attenuating brain injury, by mitophagy. Here, we identified the involvement of BNIP3L/NIX in cerebral ischemia-reperfusion (I-R)-induced mitophagy. Bnip3l knockout (bnip3l−/−) impaired mitophagy and aggravated cerebral I-R injury in mice, which can be rescued by BNIP3L overexpression. The rescuing effects of BNIP3L overexpression can be observed in park2−/− mice, which showed mitophagy deficiency after I-R. Interestingly, bnip3l and park2 double-knockout mice showed a synergistic mitophagy deficiency with I-R treatment, which further highlighted the roles of BNIP3L-mediated mitophagy as being independent from PARK2. Further experiments indicated that phosphorylation of BNIP3L serine 81 is critical for BNIP3L-mediated mitophagy. Nonphosphorylatable mutant BNIP3LS81A failed to counteract both mitophagy impairment and neuroprotective effects in bnip3l−/− mice. Our findings offer insights into mitochondrial quality control in ischemic stroke and bring forth the concept that BNIP3L could be a potential therapeutic target for ischemic stroke, beyond its accepted role in reticulocyte maturation.
Integration of Preventing Mother-To-Child Transmission of HIV and Syphilis Testing and Treatment in Antenatal Care Services in the Northern Cape and Gauteng Provinces, South Africa

Background South Africa recommends universal syphilis and HIV testing in pregnancy, with prompt antiretroviral therapy or penicillin treatment for women testing positive. Methods We used a multistage, purposeful sampling strategy to retrospectively identify clinical records from a sample (7.3%) of 32,518 women delivering from January 2005 to June 2006 at 6 public clinics in the Northern Cape and Gauteng. Descriptive analyses and logistic regression were used to assess coverage and factors related to testing and treatment of HIV and syphilis. Results Of 2379 women sampled, 93% accessed antenatal care (ANC) services during pregnancy and 71% before the third pregnancy trimester. Testing during pregnancy or delivery was 74% for HIV and 84% for syphilis; testing at the first ANC visit was 41% and 71%; and infection prevalence at delivery was 14% and 5%, respectively. Of 243 women with reactive HIV tests, 104 (43%) had treatment documented (single-dose nevirapine) before delivery. Of 98 women with reactive syphilis tests, 73% had documented receipt of 1 penicillin injection and 36% had all 3 recommended injections. Multivariable analysis found women tested for syphilis were almost 4 times more likely to have had no HIV test compared with those without syphilis testing (adjusted odds ratios, 3.9; 95% confidence interval, 1.7–5.5). Conclusions Integration and provision of a package of HIV and syphilis testing at the first ANC visit and decentralizing treatments of both infections to primary care settings could increase the coverage of testing and treatment services, thus enhancing the effectiveness of current programs eliminating mother-to-child transmission of HIV and syphilis.
Engagement of circular RNA HECW2 in the nonautophagic role of ATG5 implicated in the endothelial-mesenchymal transition

ABSTRACT Endothelial-mesenchymal transition (EndoMT) is associated with damage to blood-brain barrier (BBB) integrity. Circular RNAs (circRNAs) are highly expressed in the brain and are involved in brain diseases; however, whether circRNAs regulate the EndoMT in the brain remains unknown. Our study demonstrated that circHECW2 regulated the EndoMT by directly binding to MIR30D, a significantly downregulated miRNA from miRNA profiling, which subsequently caused an increased expression of ATG5. These findings shed new light on the understanding of the noncanonical role of ATG5 in the EndoMT induced by methamphetamine (Meth) or lipopolysaccharide (LPS). The in vivo relevance was confirmed as microinjection of circHecw2 siRNA lentivirus into the mouse hippocampus suppressed the EndoMT induced by LPS. These findings provide novel insights regarding the contribution of circHECW2 to the nonautophagic role of ATG5 in the EndoMT process in the context of drug abuse and the broad range of neuroinflammatory disorders.
Distinguishing immunoglobulin G4–related disease from its pancreatobiliary mimics: Are we there now?

Immunoglobulin G subclass 4 (IgG4)-related disease is a fibroinflammatory disorder characterized histopathologically by tumefactive lesions with storiform fibrosis and an IgG4-positive, plasma cellenriched lymphocytic infiltrate. It was initially described in the late twentieth century as a sclerosing type of autoimmune pancreatitis. In 2003, extrapancreatic manifestations (e.g., biliary) were reported in a series of Japanese patients with IgG4-related (i.e., type 1 autoimmune) pancreatitis, thus giving rise to the current concept that this disorder in fact represents a systemic clinicopathological entity. Indeed, although IgG4-related pancreatitis is regarded as the most frequent manifestation of IgG4-related disease, synchronous and/or metachronous lesions are now known to occur, with considerable frequency, in a variety of organs. In many cases of IgG4-related disease (pancreatic or otherwise), increased concentrations of IgG4 can be detected in peripheral blood. Of the four subclasses of the IgG isotype, IgG4 is the least abundant among healthy individuals, was the last to be discovered, and may perhaps be the most immunobiologically enigmatic. Its serum concentrations are highly variable among, yet fluctuate minimally within, healthy individuals, the mechanisms of which are uncertain. Indeed, the biosynthesis of IgG4 is poorly understood, though recent data suggest that interleukins 4, 10, and 12 play an inductive role. Owing to amino acid residue differences in the constant (ostensibly the structural hinge) region of the IgG4 protein, half-IgG4 molecules can become detached and combine with other halfmolecules through a process referred to as “antigenbinding fragment (Fab) arm exchange,” thereby forming asymmetrical, bispecific antibodies. Because of this unique phenomenon, IgG4 has low Fc receptor and complement binding affinity and, intriguingly, can in fact function as an anti-inflammatory mediator. Despite the aforementioned, an increased serum concentration of IgG4 protein is a diagnostic biomarker of IgG4related disease which provides a readily available, noninvasive clinical clue suggesting this diagnosis. However, approximately 30% of patients with IgG4-related pancreatitis (and/or cholangiopathy) have normal levels of serum IgG4; moreover, elevated IgG4 levels can be seen in up to 30% of patients with primary sclerosing cholangitis (PSC) or pancreatobiliary malignancy, which may also share imaging characteristics with IgG4related disease. Considering the nature of this differential and the challenges in making an accurate diagnosis, a multimodal evaluation is typically required for suspected IgG4-related disease. Perhaps the most widely referenced diagnostic criteria in this context are embodied in the acronym “HISORt,” Abbreviations: BCR, B-cell receptor; IgG, immunoglobulin G; PCR, polymerase chain reaction; qPCR, quantitative PCR; PSC, primary sclerosing cholangitis.
A highly specific and sensitive hepatitis C virus antigen enzyme immunoassay for One‐step diagnosis of viremic hepatitis C virus infection

The current standard in diagnosing hepatitis C virus (HCV) infection requires two sequential steps: anti‐HCV test to screen, followed by HCV RNA reverse‐transcription polymerase chain reaction to confirm viremic HCV (V‐HCV) infection. HCV core antigen tests provided potential for possible one‐step diagnosis. However, low sensitivity and specificity limit their clinical utility. The present study developed a novel HCV antigens enzyme immunoassay (HCV‐Ags EIA) and assessed its sensitivity, specificity, and utility for one‐step diagnosis of V‐HCV infection using 365 serum specimens, including 176 without and 189 with V‐HCV infection. First, we confirmed the presence of HCV nonstructural proteins 3, 4b, and 5a besides HCV core antigen during HCV infection and developed a novel HCV‐Ags EIA through simultaneous detection of all four HCV proteins. For the first time, the present study demonstrated that serum sample denaturation decreases the test specificity due to release of HCV‐Ags sequestered in HCV immune complexes and should not be used in any HCV‐Ags, including all the current HCV core antigen assays. On the other hand, using sample nondenaturation, the HCV‐Ags EIA results showed 98.9% specificity and 100% sensitivity compared to serum anti‐HCV and HCV RNA reverse‐transcription polymerase chain reaction results. Using serum sample dilution, and nondenaturation, the lowest limits of detection of the HCV‐Ags EIA were equivalent to serum HCV RNA levels of approximate 150‐250 IU/mL. Conclusions: The highly specific and sensitive HCV‐Ags EIA developed in the present study has the lowest limit of detection equivalent to serum HCV RNA levels of 150‐250 IU/mL; using nondenaturation of serum samples, our HCV‐Ags EIA reliably differentiated V‐HCV infection from resolved HCV infection, accomplishing screening and diagnosis of V‐HCV infection in one step. (Hepatology 2016;64:415‐424)
Time From HIV Diagnosis to Viral Load Suppression: 2007–2013

Background US guidelines now recommend that all HIV-infected persons receive antiretroviral therapy). HIV prevention is increasingly focused on ensuring that infected persons are diagnosed soon after HIV acquisition and quickly link to care and initiate antiretroviral therapy. We examined trends in time from HIV diagnosis to viral load suppression in King County, WA, to gauge improvement in our HIV care continuum over time. Methods We used HIV surveillance data and Cox proportional hazards to evaluate how the time from diagnosis to viral suppression changed among persons newly diagnosed as having HIV in King County, WA, between 2007 and 2013. Results A total of 1490 (84%) of 1766 newly diagnosed persons achieved viral suppression in a median time of 213 days (95% confidence interval, 203–229). Thirty-six percent of all persons diagnosed in 2007 and 77% in 2013 were virally suppressed within 12 months of HIV diagnosis (P < 0.0001). Differences in time to suppression by calendar year persisted when stratifying by CD4 count at diagnosis. Race was not significantly associated with time to viral suppression. Conclusions Time from HIV diagnosis to viral suppression dramatically declined between 2007 and 2013, and more than three quarters of recently HIV-diagnosed individuals in King County, WA, now achieve viral suppression within a year of diagnosis. This improvement was evident among all persons newly diagnosed as having HIV, regardless of race/ethnicity or CD4 count at time of diagnosis.
Reply to R Rylander

In a recent study, we showed that a diet low in carbohydrates and high in protein enhanced all-cause and cardiovascular mortality in elderly Swedish men (1). Other studies have found similar relations (2, 3), but the underlying mechanism remains elusive. In his letter, Rylander proposes a diet-induced disruption of the acid-base balance as a possible explanation, with subsequent effects on mineral status and cardiac function. This effect would be mediated by the high protein amounts in the diet, especially in combination with a low intake of vegetables. Interestingly, a recent study in American men and women found that a vegetable-based diet that was low in carbohydrates and high in protein was health promoting (4), supporting the suggestion by Rylander. The low intake of carbohydrates in itself might not be harmful. However, such a diet is often accompanied by a high intake of animal fat and protein, with a range of possible adverse effects, such as affecting vascular function (5). The mechanisms proposed by Rylander may also have an effect in this scenario. Collectively, these findings clearly underline the importance of high vegetable consumption, especially when the macronutrient consumption is dominated by fat and protein.
Greek Registered Nurses’ Job Satisfaction in Relation to Work-Related Stress. A Study on Army and Civilian Rns.

Background: Job satisfaction and work-related stress effect, job turnover, and patient satisfaction in nursing.Aim: To present the views of Greek Army Registered Nurses and Civilian Registered Nurses on job satisfactionand job stress and why they are lead to seeking employment elsewhere.Methods: A descriptive, cross-sectional study was undertaken by questionnaire on a random sample of 117Registered Nurses (77 Army RNs – 40 Civilian RNs), (Response rate 42%). The Warr-Cook-Wall jobsatisfaction scale was used to measure overall job satisfaction. Job related tension index was used to measurenurses’ levels of stress. The association between relationship factors and organizational outcomes such as jobsatisfaction, turnover intentions and organizational commitment were assessed. The analysis was made with theuse of SPSS (version 15). Results: Mean score of stress was for Army Registered Nurses (RNs) m=31.61 (SD 9.041 min=21 max=75)while for Civilian Registered Nurses was m=29.38 (SD 7.117 min=12 max=46) The most frequently mentionedsource of job stress for civilian RNs is not having a say on the appearance and structure of their workenvironment (p=0.017). Not being appreciated and not treated as equal to other health professionals. (p