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Abstract Background In 2016, the American College of Obstetricians and Gynecologists recommended antenatal corticosteroids in the late preterm period for women at risk for preterm delivery. Limited real-world evidence exists on neonatal outcomes, particularly for twin gestations, following the guideline change. The study objective is to determine the association of antenatal corticosteroids in late preterm singleton and twin pregnancies with respiratory complications and hypoglycemia in a real-world clinical setting. Methods This is a retrospective cohort study comprising late preterm deliveries (4,341 mother–child pairs) within the Mount Sinai Health System, 2012–2018. The exposure of interest is antenatal corticosteroid administration of betamethasone during pregnancy between 34 0/7 and 36 6/7 weeks. Our primary outcomes are neonatal respiratory complications and hypoglycemia. Multivariable logistic regression was used to estimate the association between antenatal corticosteroid exposure and these two outcomes. We stratified the study population by singleton gestations and twins to minimize the potential confounding from different obstetric management between the two groups. Results Among a total of 4,341 mother–child pairs (3,309 singleton and 1,032 twin mother–child pairs), 745 mothers received betamethasone, of which 40.94% (305/745) received the full course. Relative to no treatment, a full course of betamethasone was associated with reduced odds of respiratory complications (OR = 0.53, 95% CI:[0.31–0.85], p

BackgroundSigning Deaf South Africans have limited access to health information and, consequently, limited knowledge about health. Maternal and neonatal mortality rates are high. Cell phone use is high, making it a potentially effective way of communicating about maternal and child health. ObjectiveThe primary aim of this study was to assess whether an SMS text messaging–based health information campaign could improve knowledge about pregnancy, antenatal care, and healthy living during pregnancy for signing Deaf South African women of reproductive age. The secondary aim was to evaluate the acceptability of such an intervention. MethodsThis study was designed as a pretest-posttest study. A baseline questionnaire assessed participants’ knowledge about pregnancy, antenatal care, and healthy living during pregnancy before an SMS text messaging–based information campaign was conducted. After the campaign, an exit questionnaire was administered containing the same questions as the baseline questionnaire with additional questions on general acceptability and communication preferences. The results were compared between baseline and exit using the McNemar and Wilcoxon signed rank tests. A focus group aimed to obtain further information on the impact and acceptability of SMS text messages. The focus group was analyzed inductively. ResultsThe study showed a statistically significant improvement in overall health knowledge among participants. Despite this, some participants found the medical terminology challenging to understand. Several ways of improving SMS text messaging campaigns for the Deaf were identified, including using Multimedia Messaging Services with a person signing messages and linking information campaigns to a communication service that would enable Deaf people to pose questions. The focus group also suggested that SMS text messages might play a role in motivating healthy behaviors during pregnancy. ConclusionsThe SMS text messaging campaign effectively improved Deaf women’s knowledge about pregnancy, antenatal care, and healthy living during pregnancy and has the potential to affect health behavior. This contrasts with a similar study on hearing pregnant women. This suggests that SMS text messages may be particularly effective in improving Deaf people’s health knowledge. However, attention should be paid to Deaf participants’ specific needs and communication preferences to optimize impact. The potential of using SMS text messaging campaigns to affect behavior should be studied. Trial RegistrationPan-African Clinical Trials Registry (PACTR) PACTR201512001352180; https://tinyurl.com/3rxvsrbe

Abstract Preeclampsia is a heterogeneous and complex disease associated with rising morbidity and mortality in pregnant women and newborns in the US. Early recognition of patients at risk is a pressing clinical need to reduce the risk of adverse outcomes. We assessed whether information routinely collected in electronic medical records (EMR) could enhance the prediction of preeclampsia risk beyond what is achieved in standard of care assessments. We developed a digital phenotyping algorithm to curate 108,557 pregnancies from EMRs across the Mount Sinai Health System, accurately reconstructing pregnancy journeys and normalizing these journeys across different hospital EMR systems. We then applied machine learning approaches to a training dataset (N = 60,879) to construct predictive models of preeclampsia across three major pregnancy time periods (ante-, intra-, and postpartum). The resulting models predicted preeclampsia with high accuracy across the different pregnancy periods, with areas under the receiver operating characteristic curves (AUC) of 0.92, 0.82, and 0.89 at 37 gestational weeks, intrapartum and postpartum, respectively. We observed comparable performance in two independent patient cohorts. While our machine learning approach identified known risk factors of preeclampsia (such as blood pressure, weight, and maternal age), it also identified other potential risk factors, such as complete blood count related characteristics for the antepartum period. Our model not only has utility for earlier identification of patients at risk for preeclampsia, but given the prediction accuracy exceeds what is currently achieved in clinical practice, our model provides a path for promoting personalized precision therapeutic strategies for patients at risk.

We determined baseline oral and cervicogenital human papillomavirus (HPV) prevalence and determinants of infection in the Michigan HPV and Oropharyngeal Cancer (MHOC) study. We enrolled 394 college-age and older participants of both sexes in Ann Arbor, Michigan and the surrounding area. All participants provided an oral sample at baseline, and 130 females provided a cervicogenital sample. Samples were tested for 18 HPV genotypes using polymerase chain reaction (PCR) MassArray. Participants filled out sociodemographic and behavioral questionnaires. Prevalence ratios for HPV oral or cervicogenital prevalence by predictor variables were estimated in univariable log-binomial models. Analysis was conducted 2018-20. In the full cohort, baseline oral HPV prevalence was 10.0% for any detected genotype (among the 338 valid oral tests at baseline) and 6.5% for high-risk types, and cervicogenital prevalence was 20.0% and 10.8%, respectively (among the 130 first valid cervicogenital tests). Oral HPV prevalence did not vary by sex, with 10.5% of women and 9.0% of men having an infection. We found a high prevalence of oral and cervicogenital HPV infection in college-age participants reporting no lifetime sexual partners. Reporting a single recent partner was associated with a lower oral HPV prevalence (PR 0.39, 95% CI: 0.16, 0.96) than reporting no recent (but at least one ever) partner. No similar protective effect was seen for cervicogenital HPV. Both oral and cervicogenital prevalence increased with the number of recent partners for most sexual behaviors. We observed an ecological fallacy masking the direction of impact of vaccination on HPV prevalence in the full cohort compared to the college-aged and the age 23+ populations considered separately. Substance use was not significantly associated with oral or cervicogenital HPV infection. Many studies report substantially higher oral HPV infection prevalence in men than in women. That difference may not be uniform across populations in the US.

BackgroundNondaily smoking has been on the rise, especially in Mexico. While Mexico has strengthened its tobacco control policies, their effects on nondaily smokers have gone largely unexamined. We developed a simulation model to estimate the impact of tobacco control policies on daily and nondaily smoking in Mexico.MethodsA previously validated Mexico SimSmoke model that estimated overall trends in smoking prevalence from 2002 through 2013 was extended to 2018 and adapted to distinguish daily and nondaily smoking prevalence. The model was then validated using data from Mexican surveys through 2016. To gauge the potential effects of policies, we compared the trends in smoking under current policies with trends from policies kept at their 2002 levels.ResultsBetween 2002 and 2016, Mexico SimSmoke underestimated the reduction in male and female daily smoking rates. For nondaily smoking, SimSmoke predicted a decline among both males and females, while survey rates showed increasing rates in both genders, primarily among ages 15-44. Of the total reduction in smoking rates predicted by the model by 2018, tax policies account for more than 55%, followed by health warnings, cessation treatment, smoke-free air laws, and tobacco control spending.ConclusionsAlthough Mexico SimSmoke did not successfully explain trends in daily and nondaily smoking, it helps to identify gaps in surveillance and policy evaluation for nondaily smokers. Future research should consider appropriate measures of nondaily smoking prevalence, trajectories between daily and nondaily smoking, and the separate impact of tobacco control policies on each group.

Research on the role of neighbourhood-level deprivation in low- and middle-income countries with respect to tobacco use is relatively nascent. In South Africa, where race and deprivation are closely linked due to the history of apartheid, smoking disparities exist by individual risk factors such as gender, race, and socioeconomic status. However, less is known about how community-level factors affect smoking disparities in the country, or how the relationship between deprivation and smoking differs by race. We used data from the 2008 South African National Income Dynamics Study (NIDS) and Poisson generalised estimating equations to assess the relationship between neighbourhood deprivation and current smoking for individuals nested within neighbourhoods, while controlling for individual-level and household-level covariates. Subgroup analyses for racial categories Black and Coloured were performed. We found that the relationship between neighbourhood deprivation and smoking prevalence was non-linear: the smoking prevalence ratio was highest among those in the middle range for our deprivation index, and lower at extremely high and low levels of deprivation. Both Black and Coloured subsamples exhibited this inverted U-shape, although the relationship was weaker in the latter group. That the relationship between neighbourhood deprivation and smoking is non-linear contrasts with what has been found in high-income countries, where the relationship between neighbourhood deprivation and smoking is linear. Moreover, these findings are relevant to assess the potential differential impact of smoking interventions as a function of socioeconomic and environmental context. Keywords: Smoking, South Africa, Residential characteristics, Epidemiology

Introduction: Public health surveillance of smoking prevalence is essential in gauging the magnitude of the problem, identifying groups most affected, and evaluating polices. However, little attention has focused on how prevalence is measured, particularly in low- and middle-income countries, where smoking patterns may not mirror those in high-income countries and where the burden of tobacco use is rapidly growing. Mexico provides a unique opportunity to gauge how the questions used to define established smokers can affect prevalence estimates. This study assesses how using the 100-cigarette lifetime question to define smoking status affects estimates of smoking prevalence. Methods: We consider data from four nationally representative surveys in Mexico, from 2002 to 2016. These surveys ask about current smoking even for adults who do not indicate having smoked 100 cigarettes in their lifetime. We compare estimates of daily and nondaily smoking prevalence by age and gender with and without the 100-cigarette screen. Results: The relative difference in prevalence estimates with and without the screen was greater for nondaily than daily smoking and for females than males. The difference was especially pronounced for nondaily smokers aged 15–24, where there was a 50%–75% relative difference in estimates, albeit smaller discrepancies (20–49% relative difference) were also found among older smokers. In recent years, the relative difference was greatest at lower levels of educational attainment. Conclusions: With the growth in nondaily smoking, using the 100-cigarettes screen to define smoking status can have important implications regarding size of smoking population. Further research is warranted in other countries.

Abstract Background Signing Deaf South Africans have limited access to health information. As a result, their knowledge about health is limited. Cell phone usage in South Africa is high. This study aimed to assess whether a short message service (SMS)-based health promotion campaign could improve Deaf people’s knowledge of hypertension and healthy living. Additionally, the study aimed to assess the acceptability of using SMSs for health promotion targeting Deaf people. Methods A baseline questionnaire assessed participants’ knowledge about hypertension before an SMS-based information campaign was conducted. After the campaign, an exit questionnaire was conducted, containing the same questions as the baseline questionnaire with additional questions about general acceptability and communication preferences. Results were compared between baseline and exit, using McNemar’s test, paired t-test and Wilcoxon signed-rank test. Focus groups aimed to get further information on the impact and acceptability of SMSs. The focus groups were analysed using inductive thematic analysis. Results The campaign recruited 82 participants for the baseline survey, but due to significant loss-to-follow-up and exclusions only 41 participants were included in the analysis of the survey. The majority (60%) were men. Eighty percent were employed, while 98% had not finished high school. The campaign showed a statistically significant improvement in overall knowledge about hypertension and healthy living amongst participants. Six individual questions out of 19 also showed a statistically significant improvement. Despite this, participants in focus groups found the medical terminology difficult to understand. Several ways of improving SMS campaigns for the Deaf were identified. These included using using pictures, using ‘signed’ SMSs, combining SMSs with signed drama and linking SMS-campaigns to an interactive communication service that would enable the Deaf to pose questions for clarification. Focus groups suggested that participants who were hypertensive during the campaign adopted a healthier lifestyle. Conclusion SMSs were effective in improving Deaf people’s knowledge of hypertension and healthy living. However, SMS-campaigns should be cognizant of Deaf people’s unique needs and communication preference and explore how to accommodate these. Trial registration The research was registered with the Pan African Clinical Trial Registry on December 1, 2015. Identification number: PACTR201512001353476 .

Background Mexico has one of the most substantial burden of tobacco-related illnesses in the world where smoking causes more than 60000 deaths per year in the country. Examining smoking patterns for different birth cohorts would provide valuable insight into the impact of tobacco control policies. Methods Using smoking data for adults (age>=20) from Encuesta Nacional de Salud (National Health Survey; 2000) and Encuesta Nacional de Salud y Nutricion (National Health and Nutrition Surveys: 2006, 2012, 2016), we evaluated smoking trends by gender through age-period-cohort models with restricted cubic splines. Specifically, temporal effects by age, period, and birth cohort (1905-1990) on the prevalence of ever and current smoking were estimated. In combination with these estimates, a methodology developed by the Cancer Intervention and Surveillance Modeling Network Lung group is used to reconstruct smoking histories by cohort and gender for Mexico population based on these cross-sectional surveys. Results As expected, levels of ever and current smoking prevalence are higher for men compared to women. The prevalence of ever smokers has been decreasing in both sexes across all birth cohorts, with a sharper rate of decrease for women. Current smoking prevalence has also been declining in both sexes across all birth cohorts. The rates of decrease for current smoking differ between men and women, however; the prevalence of current smokers in men decreased at a faster rate for cohorts born before 1960 compared to women. Moreover, current smoking has been decreasing across all ages in both men and women. Conclusions This is the first attempt to study smoking trends in Mexico using age-period-cohort models. The resulting estimates will help us reconstruct smoking histories, shedding light on patterns of smoking initiation and cessation in the population over time. Together, this information could inform tobacco control interventions to decrease the burden of tobacco-related illnesses in the country.

Background: Severe acute respiratory syndrome (SARS) is a novel infectious disease with global impact. A virus from the family Coronaviridae has been identified as the cause, but the pathogenesis is still unclear.Methods: Post-mortem tissue samples from six patients who died from SARS in February and March, 2003, and an open lung biopsy from one of these patients were studied by histology and virology. Only one full autopsy was done. Evidence of infection with the SARS-associated coronavirus (SARS-CoV) and human metapneumovirus was sought by reverse-transcriptase PCR and serology. Pathological samples were examined by light and electron microscopy and immunohistochemistry.Findings: All six patients had serological evidence of recent infection with SARS-CoV. Diffuse alveolar damage was common but not universal. Morphological changes identified were bronchial epithelial denudation, loss of cilia, and squamous metaplasia. Secondary bacterial pneumonia was present in one case. A giant-cell infiltrate was seen in four patients, with a pronounced increase in macrophages in the alveoli and the interstitium of the lung. Haemophagocytosis was present in two patients. The alveolar pneumocytes also showed cytomegaly with granular amphophilic cytoplasm. The patient for whom full autopsy was done had atrophy of the white pulp of the spleen. Electron microscopy revealed viral particles in the cytoplasm of epithelial cells corresponding to coronavirus.Interpretation: SARS is associated with epithelial-cell proliferation and an increase in macrophages in the lung. The presence of haemophagocytosis supports the contention that cytokine dysregulation may account, at least partly, for the severity of the clinical disease. The case definition of SARS should acknowledge the range of lung pathology associated with this disease. [ABSTRACT FROM AUTHOR]

Background: There is no consensus on whether intravenous rehydration must be added after preoperative phenoxybenzamine (PXB) administration for pheochromocytoma. The aim of this study is to investigate whether abandonment of intravenous volume expansion after PXB administration is associated with intraoperative hemodynamic instability., Methods: 83 Patients with pheochromocytoma received surgical treatment in the Department of Urology, Handan First Hospital, between October 2014 and July 2022. All patients were subclassified into either the hemodynamic stability group (HS group) or the hemodynamic instability group (HU group) according to whether intraoperative hemodynamic instability occurred, with 51 cases in HS group and 32 cases in HU group. Differences in data between the two groups were examined, and the risk factors for intraoperative hemodynamic instability were analyzed using logistic regression., Results: The results of the analysis showed no statistically significant differences in age, sex, location of the tumor, surgical method, body mass index (BMI) ≥ 24 kg/m 2 , blood and urine catecholamine test results, preoperative oral PXB followed by combined intravenous volume expansion, proportion of patients with hypertension or diabetes mellitus or coronary heart disease between the two groups (P>0.05). The size of the tumor in the HS group was smaller than that in the HU group (5.3 ± 1.9 cm vs 6.2 ± 2.4 cm P=0.010). Multivariate analyses demonstrated that abandonment of intravenous volume expansion after preoperative receipt of α-blockers in patients with adrenal pheochromocytoma was not an independent risk factor for intraoperative hemodynamic instability. Only the tumor size (P=0.025) was an independent risk factor for intraoperative hemodynamic instability., Conclusion: The purpose of general preoperative intravenous fluid expansion is to prevent hypotension after the tumor has been resected. In the current study, we indicated that preoperative management of pheochromocytomas using the α-blocker PXB in combination with intravenous volume expansion does not further reduce the risk of intraoperative hemodynamic instability or postoperative complications compared with oral PXB alone. Therefore, our study supports preoperative management of pheochromocytoma with a single α-blocker, PXB, as sufficient., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Yan, Tian, Wu, Cai and Guo.)

The role of Abraxas 2 (ABRO1 or KIAA0157), a component of the lysine63-linked deubiquitinating system, in the cardiomyocyte proliferation and myocardial regeneration is unknown. Here, we found that ABRO1 regulates cardiomyocyte proliferation and cardiac regeneration in the postnatal heart by targeting METTL3-mediated m 6 A methylation of Psph mRNA. The deletion of ABRO1 increased cardiomyocyte proliferation in hearts and restored the heart function after myocardial injury. On the contrary, ABRO1 overexpression significantly inhibited the neonatal cardiomyocyte proliferation and cardiac regeneration in mouse hearts. The mechanism by which ABRO1 regulates cardiomyocyte proliferation mainly involved METTL3-mediated Psph mRNA methylation and CDK2 phosphorylation. In the early postnatal period, METTL3-dependent m 6 A methylation promotes cardiomyocyte proliferation by hypermethylation of Psph mRNA and upregulating PSPH expression. PSPH dephosphorylates cyclin-dependent kinase 2 (CDK2), a positive regulator of cell cycle, at Thr14/Tyr15 and increases its activity. Upregulation of ABRO1 restricts METTL3 activity and halts the cardiomyocyte proliferation in the postnatal hearts. Thus, our study reveals that ABRO1 is an essential contributor in the cell cycle withdrawal and attenuation of proliferative response in the postnatal cardiomyocytes and could act as a potential target to accelerate cardiomyocyte proliferation and cardiac repair in the adult heart., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Flexible ureteroscopic incision and drainage is a relatively new surgical method for treating parapelvic cysts. Considering that the intraoperative localization of the cyst may fail with a flexible ureteroscope, we use an innovative ultrasound-guided method to locate the cystic wall during flexible ureteroscopic surgery., Methods: We retrospectively reviewed 17 consecutive cases of parapelvic renal cysts treated by ultrasound-guided flexible ureteroscopy between March 2017 and May 2020. The differences between the simple flexible ureteroscopic technique and ultrasound-guided flexible ureteroscopic technique were compared. The surgical procedures, postoperative complications, results and patient follow-ups were evaluated., Results: The cyst wall was seen clearly in 10 patients with ureteroscopic vision. Another 7 patients underwent ultrasound-guided flexible ureteroscopic surgery since it was difficult to identify the cyst wall. The mean operative time was 25.9 ± 8.7 min and 37.1 ± 10.1 min for the conventional and modified techniques, respectively (P = 0.004); the mean time to search for cysts was 17.6 ± 5.8 min and 26.5 ± 8.4 min, respectively (P = 0.002); and the mean incision time was 7.1 ± 4.9 min and 12.1 ± 5.6 min, respectively (P = 0.000). All of the patients were followed-up for 12 months, and no serious complications or recurrence were observed., Conclusions: We demonstrated that it is feasible and safe to treat parapelvic renal cysts by ultrasound-guided flexible ureteroscopic incision and drainage. The small sample size and need for further studies were the limitations of our work., (© 2022. The Author(s).)

Background: Primary CoQ deficiency occurs because of the defective biosynthesis of coenzyme Q, one of the key components of the mitochondrial electron transport chain. Patients with this disease present with a myriad of non-specific symptoms and signs, posing a diagnostic challenge. Whole-exome sequencing is vital in the diagnosis of these cases., Case: Three unrelated cases presenting as either encephalopathy or cardiomyopathy have been diagnosed to harbor a common pathogenic variant c.370G > A in COQ4. COQ4 encodes a key structural component for stabilizing the multienzymatic CoQ biosynthesis complex. This variant is detected only among East and South Asian populations., Conclusions: Based on the population data and our case series, COQ4-related mitochondriopathy is likely an underrecognized condition. We recommend including the COQ4 c.370G > A variant as a part of the screening process for mitochondriopathy in Chinese populations., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: The adult mammalian cardiomyocytes lose their proliferative capacity, which is responsible for cardiac dysfunction and heart failure following injury. The molecular mechanisms underlying the attenuation of adult cardiomyocyte proliferation remain largely unknown. Because long noncoding RNAs (lncRNAs) have a critical role in the development of cardiovascular problems, we investigated whether lncRNAs have any role in the regulation of cardiomyocyte proliferation and cardiac repair., Methods: Using bioinformatics and initial analysis, we identified an lncRNA, named CPR (cardiomyocyte proliferation regulator), that has a potential regulatory role in cardiomyocyte proliferation. For in vivo experiments, we generated CPR knockout and cardiac-specific CPR-overexpressing mice. In isolated cardiomyocytes, we used adenovirus for silencing (CPR-small interfering RNA) or overexpressing CPR. To investigate the mechanisms of CPR function in cardiomyocyte proliferation, we performed various analyses including quantitative reverse transcription-polymerase chain reaction, Western blot, histology, cardiac function (by echocardiography), transcriptome analyses (microarray assay), RNA pull-down assay, and chromatin immunoprecipitation assay., Results: CPR level is comparatively higher in the adult heart than in the fetal stage. The silencing of CPR significantly increased cardiomyocyte proliferation in postnatal and adult hearts. Moreover, CPR deletion restored the heart function after myocardial injury, which was evident from increased cardiomyocyte proliferation, improvement of myocardial function, and reduced scar formation. In contrast, the neonatal cardiomyocyte proliferation and cardiac regeneration were remarkably suppressed in CPR-overexpressing mice or adeno-associated virus serotype 9-CPR-overexpressing heart. These results indicate that CPR acts as a negative regulator of cardiomyocyte proliferation and regeneration. Next, we found that CPR targets minichromosome maintenance 3, an initiator of DNA replication and cell cycle progression, to suppress cardiomyocyte proliferation. CPR silenced minichromosome maintenance 3 expression through directly interacting and recruiting DNMT3A to its promoter cysteine-phosphate-guanine sites, as evident from decreased minichromosome maintenance 3 promoter methylation and increased minichromosome maintenance 3 expression in CPR knocked-down cardiomyocytes and CPR knockout mouse heart. These results were confirmed in CPR-overexpressing cardiomyocytes and CPR-overexpressing mouse heart., Conclusions: Together, our findings identified that CPR is a suppressor of cardiomyocyte proliferation and indicated that lncRNAs take part in the regulation of cardiomyocyte proliferation and cardiac repair. Our study provides an lncRNA-based therapeutic strategy for effective cardiac repair and regeneration.

Increasing evidence suggests that long noncoding RNAs (lncRNAs) play crucial roles in various biological processes. However, little is known about the effects of lncRNAs on autophagy. Here we report that a lncRNA, termed cardiac autophagy inhibitory factor (CAIF), suppresses cardiac autophagy and attenuates myocardial infarction by targeting p53-mediated myocardin transcription. Myocardin expression is upregulated upon H 2 O 2 and ischemia/reperfusion, and knockdown of myocardin inhibits autophagy and attenuates myocardial infarction. p53 regulates cardiomyocytes autophagy and myocardial ischemia/reperfusion injury by regulating myocardin expression. CAIF directly binds to p53 protein and blocks p53-mediated myocardin transcription, which results in the decrease of myocardin expression. Collectively, our data reveal a novel CAIF-p53-myocardin axis as a critical regulator in cardiomyocyte autophagy, which will be potential therapeutic targets in treatment of defective autophagy-associated cardiovascular diseases.

PIWI proteins and piRNAs primarily functions as a safeguard of germline cells by activating epigenetic regulations, silencing transposons and maintaining chromatin structure. Increasing evidences reveal that PIWI proteins and piRNAs have broader functions in many vital biological processes including cell proliferation, differentiation and survival. They have been recognized as a crucial factor in the cellular events due their role in controlling mRNA expression, turnover and translation. PIWIs, with or without its partner non-coding RNA (piRNA), govern the expression and activity of many transcription factors and signaling molecules by mastering their expression and/or post-translational modifications by directly interacting with them. In this review, we focus on the functional role of PIWI family of proteins and piRNA in physiological and pathological conditions. We compile the current knowledge about the impact of alterations of PIWI and/or piRNA on expression and activities of signaling mediators and transcriptional networks associated with cell differentiation, proliferation and survival., (Copyright © 2017. Published by Elsevier GmbH.)

Circular RNAs (circRNAs) have important roles in several cellular processes. No study has established the pathophysiological role for circRNAs in the heart. Here, we show that a circRNA (mitochondrial fission and apoptosis-related circRNA (MFACR)) regulates mitochondrial fission and apoptosis in the heart by directly targeting and downregulating miR-652-3p; this in turn blocks mitochondrial fission and cardiomyocyte cell death by suppressing MTP18 translation. MTP18 deficiency reduces mitochondrial fission and suppresses cardiomyocyte apoptosis and MI. miR-652-3p directly downregulates MTP18 and attenuates mitochondrial fission, cardiomyocyte apoptosis, and MI in vitro and in vivo. MFACR directly sequesters miR-652-3p in the cytoplasm and inhibits its activity. MFACR knockdown in cardiomyocytes and mice attenuates mitochondrial fission and MI. Our results reveal a crucial role for circRNA in regulating mitochondrial dynamics and apoptosis in the heart; as such, circRNAs may serve as a potential therapeutic avenue for cardiovascular diseases.

Psoriasis, which affects approximately 1-3% of the population worldwide, is a chronic inflammatory skin disorder characterized by epidermal keratinocytes hyperproliferation, abnormal differentiation, and inflammatory infiltration. Decrease in keratinocyte apoptosis is a specific pathogenic phenomenon in psoriasis. Chinese herbs have been used for the treatment of psoriasis in China showing promising effect in clinical trials. A traditional Chinese medicine has relatively fewer side effects with longer remission time and lower recurrence rate. The extract of Rubia cordifolia L. (EA) was previously found by us to induce HaCaT keratinocytes apoptosis. In this study we identified one of the components in Rubia cordifolia L., the anthraquinone precursor 1,4-dihydroxy-2-naphthoic acid (DHNA), induces HaCaT keratinocytes apoptosis through G0/G1 cell cycle arrest. We have also demonstrated that DHNA acts through both caspase-dependent and caspase-independent pathways. Besides, cytotoxicity and IL-1 α release assays indicate that DHNA causes less irritation problems than dithranol, which is commonly employed to treat psoriasis in many countries. Since DHNA possesses similar apoptotic effects on keratinocytes as dithranol but causes less irritation, DHNA therefore constitutes a promising alternative agent for treating psoriasis. Our studies also provide an insight on the potential of using EA and DHNA, alternatively, as a safe and effective treatment modality for psoriasis.

We report a 26-year-old man with 6 years, history of duodenal gastrointestinal stromal tumor (GIST) with liver, peritoneum and lung metastases. He presented with left eye ptosis, diplopia, left facial numbness and a left temporal fossa mass that was confirmed to be GIST with left skull and left orbit metastases. Craniectomy with cranioplasty, tumor excision and decompression were performed. There was an improvement of his visual symptoms and facial numbness. To our knowledge, this is one of the few reports of surgical management of GIST, metastasized to skull and orbit, with good symptomatic relief., (Copyright © 2011. Published by Elsevier B.V.)

Two novel Gd(III) complexes with functionalised polyaminocarboxylate macrocycles, 1,4,7-tris(carboxymethyl)-9,24-dioxo-14,19-dioxa-1,4,7,10,23- pentaazacyclododecane (L(1)) and 1,4,7-tris(carboxymethyl)-9,25-dioxo-14,17,20-trioxa-1,4,7,10,23- pentaazacyclotridecane (L(2)), were prepared in good yield. Their potential use as magnetic resonance imaging (MRI) contrast agents (CAs) was evaluated by investigating their relaxation behaviour as a function of pH, temperature and magnetic field strength. The 1/T(1) proton relaxivities at 20 MHz and 25 degrees C of GdL(1) (5.87 mM(-1) s(-1)) and GdL(2) (6.14 mM(-1) s(-1)) were found to be significantly higher than the clinically used Gd 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (Gd(DOTA)(-)) and Gd diethylenetriaminepentaethanoic acid (Gd(DTPA)(2-)). The complexes possess one water molecule in the inner coordination sphere whose mean residence lifetime was estimated to be 1.1 and 1.5 micros at 25 degrees C by variable temperature (VT) (17)O NMR spectroscopy.

Background: Systemic anaplastic large cell lymphoma (ALCL) is predominantly a nodal disease, but extranodal involvement can occur during the disease course or as the primary presentation. We report two rare cases of ALCL presenting with a pleural effusion, mimicking primary effusion lymphoma (PEL)., Cases: Two patients, a 47-year-old woman and an 81-year-old man, presented with a pleural effusion for investigation. The pleural fluid contained abundant, large, lymphoid cells with marked nuclear atypia. These neoplastic cells strongly expressed CD30 and EMA and showed a T-cell phenotype (CD3+CD45RO+ for case 1 and CD4+ for case 2). Case 1, in addition, showed ALK1 expression. The tumor cells in both cases were negative for human herpes virus type 8 (HHV8) and Epstein-Barr virus (EBV). ALCL shows overlapping cytologic features with PEL, but the T-cell phenotype, ALK1 expression in case 1, lack of association with HHV8 and EBV, HIV seronegativity and subsequent discovery of nodal disease in case 2 were all in favor of ALCL over PEL., Conclusion: In rare cases a pleural effusion is the presenting feature of ALCL, and distinction from PEL depends on correlation with clinical findings, detailed immunophenotyping and study of the status of HHV8 and EBV.

Membrane-type serine protease 1 (MT-SP1) was recently cloned, and we now report its biochemical characterization. MT-SP1 is predicted to be a type II transmembrane protein with an extracellular protease domain. This localization was experimentally verified using immunofluorescent microscopy and a cell-surface biotinylation technique. The substrate specificity of MT-SP1 was determined using a positional scanning-synthetic combinatorial library and substrate phage techniques. The preferred cleavage sequences were found to be (P4-(Arg/Lys)P3-(X)P2-(Ser)P1-(Arg)P1'-(Ala)) and (P4-(X)P3-(Arg/Lys)P2-(Ser)P1(Arg) P1'(Ala)), where X is a non-basic amino acid. Protease-activated receptor 2 (PAR2) and single-chain urokinase-type plasminogen activator are proteins that are localized to the extracellular surface and contain the preferred MT-SP1 cleavage sequence. The ability of MT-SP1 to activate PARs was assessed by exposing PAR-expressing Xenopus oocytes to the soluble MT-SP1 protease domain. The latter triggered calcium signaling in PAR2-expressing oocytes at 10 nm but failed to trigger calcium signaling in oocytes expressing PAR1, PAR3, or PAR4 at 100 nm. Single-chain urokinase-type plasminogen activator was activated using catalytic amounts of MT-SP1 (1 nm), but plasminogen was not cleaved under similar conditions. The membrane localization of MT-SP1 and its affinity for these key extracellular substrates suggests a role of the proteolytic activity in regulatory events.

A case of alobar holoprosencephaly diagnosed at 10 + 3 weeks' gestation by transabdominal and transvaginal ultrasound examination followed by histological confirmation is presented. The diagnosis was based on two sonographic criteria: intracranial finding of a single ventricle with a mantle and no visible midline structures but fusion of the thalami and corpus striatum, and facial abnormalities, including hypotelorism and proboscis. The fetal karyotype was triploidy. The ultrasound findings were confirmed by pathological examination. The histological findings of proboscis, single lens and single ventricle with neural tissue remnants are presented.

We present three cases of fetal holoprosencephaly diagnosed by transabdominal and transvaginal ultrasound examinations at 10 and 13 weeks' gestation. The diagnosis was based on two sonographic criteria: first, the intracranial finding of a single ventricle with a cerebral mantle and no visible midline structures but fusion of the thalami and corpus striatum; and, second, facial abnormalities, including hypotelorism. The ultrasound findings were confirmed by embryoscopy before abortion in one case and by pathological examination after abortion in two cases. Chromosome study of the three fetuses showed trisomy 18, triploidy and mosaic 18p deletion and duplication.

Two Hong Kong Chinese adults were prescribed aconitine-containing herbal preparations by Chinese herbal practitioners for relief of minor musculoskeletal pain. After ingestion both quickly developed ventricular tachycardia followed by ventricular fibrillation and cardiac arrest refractory to resuscitation; death in both cases occurred within 12 h of ingestion. Neither had a history of cardiac disease. Coroners' autopsies showed no significant macroscopic or microscopic findings, with no evidence of ischaemic heart disease or other cardiac disease. Toxicological examination of stomach contents showed a trace of hydrolysed aconitine in one case but was negative in the other. Analysis of the herbal preparations consumed, however, confirmed the presence of the aconitine-containing herbs in quantities greatly in excess of the maximum recommended in the P.R. China pharmacopoeia. Both patients therefore consumed an accidental overdose of aconitine, which has a narrow safety margin between therapeutic analgesic effect and its known cardiotoxic effect. These particular herbal medicines are controlled substances in mainland China and Taiwan, but no controls on their dispensing exist in Hong Kong. Together with reported non-fatal cases of aconitine poisoning, these cases emphasise that legal controls of the dispensing and use of aconitine-containing herbal preparations are necessary in Hong Kong.

Vega testing (the Vega test method) is an unorthodox method of diagnosing allergic and other diseases. It has no established scientific basis and there are no controlled trials to support its usefulness. Vega testing may lead to inappropriate treatment and expense to the patient and community.

An 82 year old woman with bilateral amyloid tumours of the breast is described. Clinically, the breast masses were hard and were suspicious of carcinoma. Investigation revealed no evidence of systemic amyloidosis or amyloid related illness. Microscopically there was no neoplasia. Instead there was extensive fibrosis with amyloid deposition in perivascular periductal areas and also in the intervening stroma. The presence of amyloid was confirmed by special stains and by electron microscopy.

Five patients with heavy proteinuria and nonparasitic chyluria due to congenital abnormalities of the lymphatic system are described. Renal biopsies confirmed the clinical suspicion of an underlying glomerulonephritis. The coexistence of glomerulonephritis and chyluria in these patients was thought coincidental. Tests of value in detecting a concomitant glomerulonephritis in these patients with chyluria include urinary RBC morphology, quantitation of 24-hour urinary protein, and immunoelectrophoresis of serum and urinary proteins. Contrary to previous reports, the present study suggests that chyluria does not produce proteinuria of enough severity to cause hypoproteinemia.

The immunochemical characterization of the light chains of the mesangial immunoglobulin A (IgA) deposits were studied in 45 patients with IgA nephropathy. Kappa and lambda light chains were detected with direct immunofluorescence (IF) method, using monospecific rabbit anti-human anti-kappa and anti-lambda anti-sera. The glomeruli of 42 renal biopsies studied were strongly positive for lambda light chain, while only 25 specimens were positive for kappa light chain. Sixty-five percent of the biopsies showed a predominance of lambda light chain IF staining in the mesangial deposits. This IF pattern is unique as compared with similar studies on renal biopsies from patients with systemic lupus erythematosus, idiopathic membranous nephropathy, and normal postmortem renal tissue. The results indicate that mesangial IgA deposits in IgA nephropathy consist mainly of IgA with lambda light chains despite the fact that the normal ratio of kappa to lambda light-chain-containing immunoglobulin in human serum is two to one.

A combined retrospective and prospective study of 86 patients with IgA nephropathy was conducted to determine whether the level of proteinuria was a good predictive index of progressive disease. The patients fell into three groups: Group A, 31 patients with proteinuria of less than 1 g/day, Group B, 31 patients with proteinuria of 1 to 3.5 g/day; and Group C, 24 patients with proteinuria of more than 3.5 g/day. The groups are comparable in age of presentation, sex ratio, and duration of study and showed no difference in serum creatinine levels, creatinine clearance, incidence of hypertension or incidence of impaired renal function. Compared with the patients in the other groups, those in Group C did not have increased incidence of progressive disease. Nevertheless, they have a higher incidence of nephrotic syndrome (p less than 0.001), a lower incidence of macroscopic haematuria (p less than 0.05), lower serum albumin (p less than 0.05) and heavier proteinuria (p less than 0.01). Severity of proteinuria had no significant correlation with the severity of renal histopathologic changes. Clinical observations divided the 24 patients with nephrotic range proteinuria into three well-defined groups with different prognoses. Six patients had progressive disease with decreasing proteinuria. Five of these remained hypertensive and their initial renal biopsy showed advanced pathologic changes. Thirteen patients had persistent proteinuria although the renal function remained unchanged. Three of these were treated with steroid but failed to respond, and their renal histopathologic changes were usually moderate. The remaining five patients showed good response to steroid treatment although two became steroid-dependent. Their renal histopathology showed mild alteration. Our findings suggest that severe proteinuria in IgA nephropathy does not inevitably indicate a poor prognosis.

Fine needle aspiration cytology (FNA) and Tru-cut needle biopsy (TNB) have been used for the pre-operative diagnosis of cancer in breast masses as alternatives to open breast biopsy. The accuracy of clinical examination, fine needle aspiration biopsy and Tru-cut needle biopsy was assessed in 230 patients with palpable breast masses and the value of using both biopsy methods in the management was prospectively evaluated. Clinical diagnosis had a sensitivity of 89.2% and specificity of 78.4% (32.7% false positive, 6.5% false negative). Aspiration cytology was diagnostic in 78.4% of cancers and 71.6% of benign lesions [excluding non-diagnostic samples (27.4%), sensitivity was 96.6% and specificity was 100%]. Tru-cut needle biopsy identified 82.9% of cancers and 61.7% of benign lesions [excluding non-diagnostic samples (33.3%), sensitivity was 96.7% and specificity was 100%]. There were no false positive errors with either aspiration cytology or needle biopsy. Statistical comparison showed that there was no significant difference between aspiration cytology and needle biopsy. The combined result of both biopsies was superior to clinical examination when non-diagnostic samples were excluded. With the routine use of both biopsy techniques, frozen section was avoided in 73% of all cancers and unnecessary operations were avoided in 33.5% of patients which included breast cysts, benign mammary dysplasia and inflammatory lesions.