Post COVID-19 vaccination medium vessel vasculitis: a systematic review of case reports.

PURPOSE: Vaccinations are essential in minimizing the effects of global health crises including COVID-19 pandemic. This study investigates the potential association between COVID-19 vaccination and the occurrence of medium vessel vasculitis. METHODS: Several databases were utilized to conduct a comprehensive literature review. The studies were carefully evaluated to ensure their quality and eliminate any potential bias. RESULTS: After reviewing 935 search results and removing duplicates, we selected 10 case reports. We discovered that medium vessel vasculitis may occur after COVID-19 vaccination, typically appearing around 16.2 days after vaccination. The patients in the study had a median age of 43.5 years and were predominantly males (80%). Additionally, half of the cases were reported after the second dose of vaccination. CONCLUSIONS: Vaccination-associated vasculitis is a rare yet possible complication of COVID-19 vaccination and lacks a clear treatment protocol.

Heel Pain Management in Haglund's Deformity Targeting Sural Nerve Branches under Ultrasound Guidance: Case Report.

Introduction: Haglund's deformity is an abnormality of the bone and soft tissue of the foot, also known as retrocalcaneal exostosis, Mulholland deformity, and "pump bump". The etiology is not well known. Probable causes include a tight Achilles tendon, a high arch of the foot, and hereditary. The clinical features consist of pain at the posterior aspect of the heel which is predominantly present when the patient begins to walk after a period of rest or inactivity. Case Report: We report a case of a 60-year-old teacher with left heel pain for 3 years, unable to stand or walk for more than 15 min due to pain. We diagnosed him as a case of Haglund's deformity and treated him with ultrasound-guided injections targeting the superficial branches of the sural nerve. This case report illustrates a rarely described modality for the management of heel pain due to Haglund's deformity. Targeting superficial branches of the Sural nerve under ultrasound guidance can act as a superior treatment modality for the management of heel pain due to Haglund's deformity. Conclusion: Haglund's deformity is a cause of pain in the hindfoot that should be taken into account in the differential diagnosis of any patient presenting with heel pain. Ultrasonography has proved to be an important cost-effective tool in the diagnosis and management of various ankle pathologies like Haglund's deformity, thereby reducing the sole dependence on surgical management. Targeting the superficial (cutaneous) branches of the sural nerve can give satisfactory long-term relief of heel pain in patients with Haglund deformity.

APOE2 Heterozygosity Reduces Hippocampal Soluble Amyloid-ß42 Levels in Non-Hyperlipidemic Mice.

APOE2 lowers Alzheimer's disease (AD) risk; unfortunately, the mechanism remains poorly understood and the use of mice models is problematic as APOE2 homozygosity is associated with hyperlipidemia. In this study, we developed mice that are heterozygous for APOE2 and APOE3 or APOE4 and overexpress amyloid-ß peptide (Aß) (EFAD) to evaluate the effect of APOE2 dosage on Aß pathology. We found that heterozygous mice do not exhibit hyperlipidemia. Hippocampal but not cortical levels of soluble Aß42 followed the order E2/2FAD > E2/3FAD≤E3/3FAD and E2/2FAD > E2/4FAD < E4/4FAD without an effect on insoluble Aß42. These findings offer initial insights on the impact of APOE2 on Aß pathology.

Association between calcium supplementation and gestational hypertension, and preeclampsia: A Meta-analysis of 26 randomized controlled trials.

BACKGROUND: Pre-eclampsia and eclampsia are common causes of morbidity and mortality, especially in low-income countries. Reducing adverse outcomes associated with hypertensive disorders of pregnancy has been the ultimate priority in recent years. We aim to evaluate the association between calcium supplementation and preeclampsia and gestational hypertension risk among pregnant women. METHODS: A systematic literature search was performed in electronic databases from inception to 15th July 2023, including only randomized controlled trials. Odds ratio (OR) were, and their corresponding 95% confidence interval (95% CI). RESULTS: A total of 26 studies with 20,038 patients (10,003 patients with calcium supplements and 10,035 patients with placebo group) were included in the analysis. The Pooled analysis of primary outcome shows that calcium supplements reduce the risk of preeclampsia by 49% (OR, 0.51(95%CI: 0.40-0.66), P<0.001), and reduce the risk of gestational hypertension by 30% (OR, 0.70 (95%CI: 0.58-0.85)), P<0.001) compared to placebo. There was a trend of lower incidence of preterm delivery (OR, 0.88 (95%CI: 0.71-1.09), P=0.23), labor induction (OR, 0.90 (95%CI: 0.78-1.03), P=0.13), small for gestational age (OR, 0.70 (95% CI:0.37-1.32), P = 0.27), low birth weight (OR, 0.96 (95%CI: 0.86-1.08), P=0.53), perinatal mortality (OR, 0.88 (95%CI: 0.72-1.09), P=0.24), and maternal mortality (OR, 0.48 (95%CI: 0.12-1.84), P=0.28) among calcium supplementation group compared with the placebo group, however, statistical signifance was not achieved. CONCLUSION: This study shows that calcium supplements are associated with a significant reduction in the risk of preeclampsia and gestational hypertension and a trend toward better maternal and fetal-related outcomes.

Association between heart failure and the incidence of cancer: a systematic review and meta-analysis.

Aims: The association between heart failure (HF) patients and the incidence of cancer is not well understood, with conflicting results to date. The aim of this meta-analysis was to evaluate whether patients with HF have a higher risk of developing cancer. Methods and results: We performed a systematic literature search using PubMed, Embase, and Scopus for relevant articles from inception until 10 December 2022. The primary clinical outcome was the incidence of cancer. Secondary endpoints were the incidence of breast cancer, lung cancer, haematological cancer, colorectal cancer, and prostate cancer. A total of 9 articles with 7 329 706 (515 041 HF vs. 6 814 665 non-HF) patients were involved in the analysis. The mean age of the patients in the HF and the non-HF groups was 69.06 and 66.76 years. The median follow-up duration was 6.7 years. The most common comorbidity among both groups includes diabetes mellitus (27.58 vs. 14.49%) and hypertension (81.46 vs. 57.38%). Patients with HF were associated with a significant increase in the incidence of cancer {hazard ratio [HR], 1.43 [95% confidence interval (CI): 1.21-1.68], P < 0.001}, breast cancer [HR, 1.28 (95% CI: 1.09-1.50), P < 0.001], lung cancer [HR, 1.89 (95% CI: 1.25-2.85), P < 0.001], haematological cancer [HR, 1.63 (95% CI: 1.15-2.33), P = 0.01], and colorectal cancer [HR, 1.32 (95% CI: 1.11-1.57), P < 0.001] compared with patients without HF. However, the incidence of prostate cancer was comparable between both groups [HR, 0.97 (95% CI: 0.66-1.43), P = 0.88]. Conclusion: This meta-analysis confirms that the state of HF is associated with a higher risk for incident cancer. These data may aid in raising awareness with physicians that cancer may develop in patients with prevalent heart failure and that early screening and evaluation may be useful in an early diagnosis of cancer.

Two-dimensional layered MoSe2/graphene oxide (GO) nanohybrid coupled with the specific immune-recognition element for rapid detection of endosulfan.

Endosulfan (En) is an organochlorine biocide (OCB), that ends up in the environment due to the enzymatic and microsomal activity even though it is not accumulated in living tissue. Endosulfan acts as an organic micro-pollutant which disrupts land as well as aquatic ecosystem. In the present study, we chemically modified endosulfan and conjugated it with a carrier protein to produce an immune response. The generated antibodies were tested for specificity against En, and characterized before further use. Transition Metal Chalcogenides (TMC) showed excellent optoelectrical potential due to its direct bandgap and distinct physical as well as chemical characteristics. Herein, we synthesized a novel nanohybrid using MoSe2 in combination with graphene oxide (GO) and characterized thoroughly. This was similar to graphene-based metal chalcogenides which were further used in this study to fabricate biosensor for the sensitive detection of En. The in-house developed antibodies (En-Ab) were coupled with the nanohybrid to make MoSe2/GO/En-Ab electrode. Fabricated electrode was tested for electrochemical parameters using differential pulse voltammetry (DPV). Working efficiency of the fabricated electrode i.e., limit of detection (LOD), was found to be 7.45 ppt. In conclusion, we hypothesized that the synthesized TMC nanohybrids could be employed for biosensing of endosulfan, and can likely be developed to test field samples.

Heterotaxy pattern associated with sinus node dysfunction in an adult: A case report.

Key Clinical Message: A 26-year-old male patient admitted to the hospital ward with experience of repetitive syncopes for a year. The patient was diagnosed with sick sinus syndrome. The aim of this clinical report is to highlight the variability of anatomical findings associated with polysplenia pattern. Abstract: This case report presents a 26-year-old male patient who presented to the medical ward with a complaint of repeating blackouts for a year. The patient was then diagnosed with sick sinus syndrome, and further investigations revealed left isomerism, polysplenia, and no congenital heart defects. Holter monitoring, ultrasonography, electrocardiography, and computed tomography were used to confirm the diagnosis. The patient underwent DDDR pacemaker implantation for the treatment of SA node dysfunction. The report highlights the variability of anatomical findings associated with polysplenia pattern and the various types of heartbeat disruptions that may occur in the atrial appendages of the left side isomerism.

Percutaneous Coronary Intervention Outcomes in Patients with Liver Cirrhosis: A Systematic Review and Meta-Analysis.

There is a paucity of data and minimal literature on outcomes of percutaneous coronary intervention (PCI) among liver cirrhosis patients. Therefore, we conducted a systematic review and meta-analysis to evaluate the clinical outcomes among liver cirrhosis patients post-PCI. We conducted a comprehensive literature search in the PubMed, Embase, Cochrane, and Scopus databases for relevant studies. Effect sizes were pooled using the DerSimonian and Laird random-effects model as an odds ratio (OR) with 95% confidence intervals (CI). A total of 3 studies met the inclusion criteria, providing data from 10,705,976 patients. A total of 28,100 patients were in the PCI + Cirrhosis group and 10,677,876 patients were in the PCI-only group. The mean age of patients with PCI + Cirrhosis and PCI alone was 63.45 and 64.35 years. The most common comorbidity was hypertension among the PCI + Cirrhosis group compared with PCI alone (68.15% vs. 73.6%). Cirrhosis patients post-PCI were had higher rates of in-hospital mortality (OR, 4.78 (95%CI: 3.39-6.75), p < 0.001), GI bleeding (OR, 1.91 (95%CI:1.83-1.99), p < 0.001, I2 = 0%), stroke (OR, 2.48 (95%CI:1.68-3.66), p < 0.001), AKI (OR, 3.66 (95%CI: 2.33-6.02), p < 0.001), and vascular complications (OR, 1.50 (95%CI: 1.13-1.98), p < 0.001) compared with the PCI group without cirrhosis. Patients with cirrhosis are at a high risk for mortality and adverse outcomes post-PCI procedure compared to the PCI-only group of patients.

Emerging Trends and Recent Progress of MXene as a Promising 2D Material for Point of Care (POC) Diagnostics.

Two-dimensional (2D) nanomaterials with chemical and structural diversity have piqued the interest of the scientific community due to their superior photonic, mechanical, electrical, magnetic, and catalytic capabilities that distinguish them from their bulk counterparts. Among these 2D materials, two-dimensional (2D) transition metal carbides, carbonitrides, and nitrides with a general chemical formula of Mn+1XnTx (where n = 1-3), together known as MXenes, have gained tremendous popularity and demonstrated competitive performance in biosensing applications. In this review, we focus on the cutting-edge advances in MXene-related biomaterials, with a systematic summary on their design, synthesis, surface engineering approaches, unique properties, and biological properties. We particularly emphasize the property-activity-effect relationship of MXenes at the nano-bio interface. We also discuss the recent trends in the application of MXenes in accelerating the performance of conventional point of care (POC) devices towards more practical approaches as the next generation of POC tools. Finally, we explore in depth the existing problems, challenges, and potential for future improvement of MXene-based materials for POC testing, with the goal of facilitating their early realization of biological applications.

Unveiling the modulation of Nogo receptor in neuroregeneration and plasticity: Novel aspects and future horizon in a new frontier.

Neurodegenerative diseases (NDs) such as Alzheimer's, Parkinson's, Multiple Sclerosis, Hereditary Spastic Paraplegia, and Amyotrophic Lateral Sclerosis have emerged as the most dreaded diseases due to a lack of precise diagnostic tools and efficient therapies. Despite the fact that the contributing factors of NDs are still unidentified, mounting evidence indicates the possibility that genetic and cellular changes may lead to the significant production of abnormally misfolded proteins. These misfolded proteins lead to damaging effects thereby causing neurodegeneration. The association between Neurite outgrowth factor (Nogo) with neurological diseases and other peripheral diseases is coming into play. Three isoforms of Nogo have been identified Nogo-A, Nogo-B and Nogo-C. Among these, Nogo-A is mainly responsible for neurological diseases as it is localized in the CNS (Central Nervous System), whereas Nogo-B and Nogo-C are responsible for other diseases such as colitis, lung, intestinal injury, etc. Nogo-A, a membrane protein, had first been described as a CNS-specific inhibitor of axonal regeneration. Several recent studies have revealed the role of Nogo-A proteins and their receptors in modulating neurite outgrowth, branching, and precursor migration during nervous system development. It may also modulate or affect the inhibition of growth during the developmental processes of the CNS. Information about the effects of other ligands of Nogo protein on the CNS are yet to be discovered however several pieces of evidence have suggested that it may also influence the neuronal maturation of CNS and targeting Nogo-A could prove to be beneficial in several neurodegenerative diseases.

Nano-assembly of multiwalled carbon nanotubes for sensitive voltammetric responses for the determination of residual levels of endosulfan.

Endosulfan (ES) is an extensively utilized agricultural pesticide in developing countries, despite its life-threatening toxic effects. In this study, we propose a sensitive detection method against endosulfan using multiwalled carbon nanotubes (MWCNT). Herein, we have conjugated endosulfan with bovine serum albumin (BSA) via zero-length conjugation method and successfully confirmed with various biophysical techniques. Endosulfan antibodies (ES-Ab) were raised in-house, fabricated on electrodes coupled with MWCNT, and optimized to achieve maximum peak current by varying the parameters such as MWCNT and antibody concentration, scan rate, temperature, pH, and response time using voltammetry. Cyclic voltammetry (CV), differential pulse voltammetry (DPV), and impedance spectroscopies (IS) were performed for electrochemical analysis. The fabricated immunosensor was also evaluated for its cross reactivity with isodrin, chlorpyrifos, and monocrotophos. The limit of detection for ES was found to be 0.184 ppt in standard buffer (range 0.001 ppt-100 ppb). Additionally, spiked ES in water, animal feed, root, and leaf extract samples were also analyzed and validated by HPLC. To summarize, the fabricated electrode can be used for successful detection of endosulfan in the agricultural sector to elude the lethal effect at large.

Lower genital tract infections between 18 and 24 weeks of pregnancy and its association with adverse pregnancy outcome.

Introduction: Lower genital tract infection (LGTI) is common among apparently healthy-looking pregnant women, and its overall prevalence is 40%-54%. LGTI is strongly associated with major adverse pregnancy outcomes such as spontaneous preterm delivery (SPTD), premature rupture of membranes (PROM), and neonatal morbidities. Materials and Methods: A prospective cohort study was performed in a tertiary care hospital in Gujarat with the objective of finding out the presence of LGTI in the second trimester and looking for its association with various adverse pregnancy outcomes. Two hundred and fifty pregnant women were screened for the presence of vaginal discharge. Various microbiological examinations were done. Diagnosis of specific LGTI was made based on the predecided criteria. Patients were followed up till delivery and maternal and neonatal outcomes were recorded. Data were compared to find out a possible association between LGTI and various adverse pregnancy outcomes such as SPTD, PROM, and neonatal deaths. Results: Out of 194 LGTI cases diagnosed, 54% were having bacterial vaginosis (BV), while 3% were diagnosed having trichomonas. While observing an association of LGTIs and adverse pregnancy outcomes, a maximum number of PROM were observed in the BV and beta Streptococcus infections group. Neonatal admissions were required in 60% of cases. Intrauterine fetal deaths and neonatal deaths were observed in only laboratory-positive cases mainly associated with beta Streptococcus infection and trichomonas. Conclusion: In this study, the most common LGTI prevalent in pregnant women was BV and the least common was trichomoniasis. There was a significant positive association present between LGTIs and adverse pregnancy outcomes such as SPTD and PROM.

Sex Differences in All-Cause Inpatient Mortality Risk in Gastric Cancer: Nationwide Inpatient Population-Based Study.

Objective The purpose of this study is to evaluate the differences in demographic characteristics, comorbidities, and hospital outcomes in gastric cancer inpatients by sex and evaluate the risk factors for in-hospital mortality in gastric cancer inpatients by sex. Methods We conducted a cross-sectional study using the nationwide inpatient sample (NIS, 2019). Our sample included 22,415 adult inpatients (age ≥18 years) hospitalized with a primary discharge diagnosis of gastric cancer that was identified by the international classification of diseases, 10th revision (ICD-10) codes of C16.x. Independent univariate binomial logistic regression models were used to evaluate the odds ratio (OR) of predictors associated with all-cause in-hospital mortality in gastric cancer inpatients by sex. Results The total number of patients admitted with gastric cancer was 22,415, out of which 62.7% were males and 37.3% were females, with the mean age at the admission of 65.5 years and 66.4 years, respectively. While studying comorbidities, we found that 41.5% percent of all patients had gastric cancer with metastasis, and there existed a significantly higher prevalence in males (42.2% vs. 40.4% in females). Other important and statistically significant comorbid conditions that were prevalent in these patients include complicated diabetes (12.2%), obesity (12.1%), depression (8%), and alcohol abuse (3.1%). Females between 50-59 years of age were at 2.5 times increased risk of mortality compared to those less than 40 years of age (OR: 2.5; 95% CI: 1.28-4.95). Conclusion Females of the age group 50-59 years are at greater risk of all-cause inpatient mortality due to gastric cancer. Black males are at increased risk of all-cause inpatient mortality compared to White males. Gastric cancer incidence and mortality rates have been down trending with the development of screening and better treatment options, but it still continues to be a major burden on the healthcare system.

Ultrasensitive immunosensing of Penicillin G in food samples using reduced graphene oxide (rGO) decorated electrode surface.

The impact of uncontrolled antibiotic use in animals has subsequently led to emergence of antibiotic-resistant bacteria among humans due to consumption of animal by-products. Hence, to investigate antibiotic contamination in animal origin food products, we have developed a reduced graphene oxide (rGO) based immunosensor using fabricated electrode conjugated with anti-Penicillin antibody (rGO/Pen-Ab) for sensitive detection of Penicillin G. To execute this, Penicillin was first conjugated with Bovine Serum Albumin (BSA) which was confirmed via chromatographic, spectroscopic and electrophoretic-based techniques against both the in-house developed Penicillin conjugate (Pen-BSA) as well as the commercial Penicillin conjugate (Com-Pen-BSA). Further, we fabricated electrode based on one step synthesized rGO and immobilized with antibodies generated against Pen-BSA (Pen-Ab), and Com-Pen-BSA (Com-Pen-Ab), separately for detection of Penicillin. Each synthesis and conjugation step was confirmed by different spectroscopic methods. For efficient working of the electrode, various parameters were optimized using Voltammetry. The limit of detection for Penicillin G against Pen-Ab and Com-Pen-Ab was determined as 0.724 pM and 0.668 pM respectively and both displayed negligible cross reactivity against other ß-lactam antibiotics (Cefalexin and Ampicillin). Furthermore, antibiotics were also detected in spiked milk, egg and meat samples and the electrode was evaluated for repeatability and storage stability. In conclusion, in-house developed Pen-Ab showed better sensitivity as compared to Com-Pen-Ab. The fabricated rGO/Pen-Ab biosensor shows future potential for rapid detection of penicillin and other ß-lactam antibiotics for safe consumption of animal by-products in humans.

Emerging Pathophysiological Mechanisms Linking Diabetes Mellitus and Alzheimer's Disease: An Old Wine in a New Bottle.

Type-2 diabetes mellitus (T2DM) is a chronic immuno-inflammatory and metabolic disease characterized by hyperglycemia and insulin resistance with corresponding hyperinsulinemia. On the other hand, Alzheimer's disease (AD) is a neurodegenerative disease involving cognitive impairment, neuronal dysfunction, and memory loss. Several recently published literatures suggest a causal relationship between T2DM and AD. In this review, we have discussed several potential mechanisms underlying diabetes-induced cognitive impairment which include, abnormal insulin signaling, amyloid-ß accumulation, oxidative stress, immuno-inflammation, mitochondrial dysfunction, advanced glycation end products, acetylcholinesterase and butyrylcholinesterase, advanced lipid peroxidation products, and apolipoprotein E. All these interconnected mechanisms may act either individually or synergistically which eventually leads to neurodegeneration and AD.

In Vitro Assessment of Intracanal Calcium Hydroxide Removal Using Various Irrigation Systems: An SEM Study.

AIM: The aim of this research was to assess the effectiveness of three different irrigation systems in elimination of calcium hydroxide [Ca(OH)2]from root canals. MATERIALS AND METHODS: This in vitro research included ninety recently extracted mandibular premolar teeth with a solitary root. The sample teeth were subjected to disinfection employing sodium hypochlorite at 5.25%. The root canal preparation was performed followed by placement of premixed Ca(OH)2 within every canal. The sample teeth were then randomly allocated into one of the three experimental groups (each comprising 30 samples) as follows: Group 1, NaviTip FX irrigation system; group 2, Vibringe sonic irrigation system; and group 3, EndoVac apical negative pressure irrigation system. Following the preparation, each of the sample teeth was examined beneath a scanning electron microscope (SEM) at a magnification of 1000×. RESULTS: An intragroup comparative analysis revealed that the highest Ca(OH)2 elimination was seen at middle third (0.82 ± 0.09, 0.30 ± 0.11) in NaviTip FX irrigation system and Vibringe sonic irrigation system, respectively. Higher Ca(OH)2 was eliminated at the apical third (0.26 ± 0.02) by the EndoVac irrigation system. At coronal third, maximum Ca(OH)2 removal was seen in EndoVac irrigation system (0.49 ± 0.03). A statistically significant difference was noted amid Vibringe sonic irrigation and EndoVac irrigation systems. The intergroup evaluation of Ca(OH)2 elimination at coronal, middle, and apical third showed a statistically significant difference between NaviTip FX irrigation and Vibringe sonic irrigation as well as between NaviTip FX irrigation and EndoVac irrigation at a p value of 0.001. The difference between EndoVac irrigation and Vibringe sonic irrigation was not statistically significant. CONCLUSION: Amid the limitations of this research, this research concludes that none among the irrigation methods employed could totally eliminate the Ca(OH)2 off the root canals. Nevertheless, EndoVac apical negative pressure irrigation has slightly superior potential in eliminating Ca(OH)2 from the root canals in comparison with Vibringe sonic irrigation as well as the NaviTip FX irrigation system. CLINICAL SIGNIFICANCE: Even though the Ca(OH)2 is largely suggested as medicament, its elimination at the point of canal obturation is likewise significant and complex as any remaining portion may avoid sealer diffusion inside the dentinal tubules, consequently substantially escalating the apical leakage of endodontically treated teeth.

The Long Noncoding RNA CCAT2 Induces Chromosomal Instability Through BOP1-AURKB Signaling.

BACKGROUND & AIMS: Chromosomal instability (CIN) is a carcinogenesis event that promotes metastasis and resistance to therapy by unclear mechanisms. Expression of the colon cancer-associated transcript 2 gene (CCAT2), which encodes a long noncoding RNA (lncRNA), associates with CIN, but little is known about how CCAT2 lncRNA regulates this cancer enabling characteristic. METHODS: We performed cytogenetic analysis of colorectal cancer (CRC) cell lines (HCT116, KM12C/SM, and HT29) overexpressing CCAT2 and colon organoids from C57BL/6N mice with the CCAT2 transgene and without (controls). CRC cells were also analyzed by immunofluorescence microscopy, γ-H2AX, and senescence assays. CCAT2 transgene and control mice were given azoxymethane and dextran sulfate sodium to induce colon tumors. We performed gene expression array and mass spectrometry to detect downstream targets of CCAT2 lncRNA. We characterized interactions between CCAT2 with downstream proteins using MS2 pull-down, RNA immunoprecipitation, and selective 2'-hydroxyl acylation analyzed by primer extension analyses. Downstream proteins were overexpressed in CRC cells and analyzed for CIN. Gene expression levels were measured in CRC and non-tumor tissues from 5 cohorts, comprising more than 900 patients. RESULTS: High expression of CCAT2 induced CIN in CRC cell lines and increased resistance to 5-fluorouracil and oxaliplatin. Mice that expressed the CCAT2 transgene developed chromosome abnormalities, and colon organoids derived from crypt cells of these mice had a higher percentage of chromosome abnormalities compared with organoids from control mice. The transgenic mice given azoxymethane and dextran sulfate sodium developed more and larger colon polyps than control mice given these agents. Microarray analysis and mass spectrometry indicated that expression of CCAT2 increased expression of genes involved in ribosome biogenesis and protein synthesis. CCAT2 lncRNA interacted directly with and stabilized BOP1 ribosomal biogenesis factor (BOP1). CCAT2 also increased expression of MYC, which activated expression of BOP1. Overexpression of BOP1 in CRC cell lines resulted in chromosomal missegregation errors, and increased colony formation, and invasiveness, whereas BOP1 knockdown reduced viability. BOP1 promoted CIN by increasing the active form of aurora kinase B, which regulates chromosomal segregation. BOP1 was overexpressed in polyp tissues from CCAT2 transgenic mice compared with healthy tissue. CCAT2 lncRNA and BOP1 mRNA or protein were all increased in microsatellite stable tumors (characterized by CIN), but not in tumors with microsatellite instability compared with nontumor tissues. Increased levels of CCAT2 lncRNA and BOP1 mRNA correlated with each other and with shorter survival times of patients. CONCLUSIONS: We found that overexpression of CCAT2 in colon cells promotes CIN and carcinogenesis by stabilizing and inducing expression of BOP1 an activator of aurora kinase B. Strategies to target this pathway might be developed for treatment of patients with microsatellite stable colorectal tumors.

Vaginal pH as a Diagnostic Tool for Menopause: A Preliminary Analysis.

INTRODUCTION: Menopause is defined as the permanent cessation of menstruation, as a result of decrease in ovarian follicles and the loss of ovarian activity. There is decrease in inhibin B level which causes decrease in negative feedback on the serum follicle-stimulating hormone (FSH), which in turn increases the level of serum FSH. Serum FSH is routinely used as a marker of menopause. Decline in the estrogen level causes thinning of vaginal epithelium, resulting in less exfoliation of the vaginal epithelial cells, lesser available glycogen, and decreased substrate for acid production, leading to increase in vaginal pH. AIMS: The aim of this study is to compare the sensitivity of vaginal pH versus serum FSH level to diagnose menopause. SETTINGS AND DESIGN: This is a cross-sectional study, performed in obstetrics and gynecology outpatient department of a teaching hospital of central Gujarat. SUBJECTS AND METHODS: A total of 120 women who had their last menstrual period >1 year back (menopause) were included in the study. Vaginal pH was measured and serum sample was taken to measure FSH level. Sensitivity of both vaginal pH and serum FSH to diagnose menopause was compared. McNemar test was used to analyze the convergence of the two methods for the diagnosis of menopause. RESULTS: In the absence of vaginal infection, sensitivity of vaginal pH to diagnose menopause was 90%, while sensitivity of the serum FSH was 85%. CONCLUSIONS: Sensitivity of the vaginal pH is similar to the serum FSH for diagnosis of menopause.

OncomiR-10b hijacks the small molecule inhibitor linifanib in human cancers.

The pervasive role of microRNAs (miRNAs) in cancer pathobiology drives the introduction of new drug development approaches such as miRNA inhibition. In order to advance miRNA-therapeutics, meticulous screening strategies addressing specific tumor targets are needed. Small molecule inhibitors represent an attractive goal for these strategies. In this study, we devised a strategy to screen for small molecule inhibitors that specifically inhibit, directly or indirectly, miR-10b (SMIRs) which is overexpressed in metastatic tumors. We found that the multi-tyrosine kinase inhibitor linifanib could significantly inhibit miR-10b and reverse its oncogenic function in breast cancer and liver cancer both in vitro and in vivo. In addition, we showed that the efficacy of linifanib to inhibit tyrosine kinases was reduced by high miR-10b levels. When the level of miR-10b is high, it can "hijack" the linifanib and reduce its kinase inhibitory effects in cancer resulting in reduced anti-tumor efficacy. In conclusion, our study describes an effective strategy to screen for small molecule inhibitors of miRNAs. We further propose that miR-10b expression levels, due to the newly described "hijacking" effect, may be used as a biomarker to select patients for linifanib treatment.

A rare and isolated presentation of primary cutaneous anaplastic large cell lymphoma.

Primary cutaneous anaplastic large cell lymphoma is a CD30+ lymphoproliferative disorder of the skin characterized by the absence of nodal and visceral involvement, low recurrence rate, spontaneous remission, and tendency to occur in patients older than 20 years. The case presented here is of a 15-year-old boy with grouped papular lesions arranged in an annular fashion with a central clearing on his right arm for 4 months that was diagnosed with a case of anaplastic lymphoma kinase-negative primary cutaneous CD30+ anaplastic large cell lymphoma. The CT scan, bone marrow biopsy, and laboratory data ruled out systemic involvement. He was treated with oral methotrexate 10 mg once a week, but was lost to follow-up.