Calretinin Staining in Anorectal Line Biopsies Accurately Distinguished Hirschsprung Disease in a Retrospective Study.

INTRODUCTION: The absence of submucosal ganglion cells does not reliably distinguish Hirschsprung disease from non Hirschsprung disease in anorectal line biopsies. Calretinin staining might be helpful in these biopsies. To determine its value, we analyzed calretinin positive mucosal neurites in anorectal line biopsies. METHODS: Two pediatric pathologists, without access to patient data, evaluated calretinin positive mucosal neurites in anorectal line junctional mucosa in archival rectal biopsies contributed by 17 institutions. A separate investigator compiled patient information and sent data for statistical analysis. RESULTS: Biopsies with anorectal junctional mucosa from 115 patients were evaluated for calretinin positive mucosal neurites. 20/20 Hirschsprung disease biopsies were negative. 87/88 non Hirschsprung disease biopsies and 7/7 post pullthrough Hirschsprung disease neorectal biopsies were positive. Statistical analysis of the 108 non pullthrough biopsies yielded an accuracy of 99.1% (sensitivity 100%, specificity 98.9%). Age range was preterm to 16 years. Biopsy size was less than 1 mm to over 1 cm. CONCLUSIONS: Absence of calretinin positive mucosal neurites at the anorectal line was highly accurate in distinguishing Hirschsprung disease from non Hirschsprung disease cases in this blinded retrospective study. Calretinin staining is useful for interpreting biopsies from the physiologic hypoganglionic zone up to the anorectal line.

Eosinophil Peroxidase Staining Enhances the Diagnostic Utility of the Cytosponge in Eosinophilic Esophagitis.

INTRODUCTION: We aimed to assess the diagnostic utility of eosinophil peroxidase (EPX) staining on Cytosponge (CS) samples in eosinophilic esophagitis (EoE). METHODS: Esophageal biopsy (BX) samples from adult subjects with EoE were assessed using peak eosinophils per high-power field (eos/hpf), EPX, and the EoE histologic scoring system. EPX staining and eos/hpf were compared (BX vs CS). RESULTS: CS EPX positivity correlated with eos/hpf (CS [ r = 0.82, P < 0.0001]; BX [ r = 0.65, P < 0.0001]) and EoE histologic scoring system (grade [ r = 0.62, P < 0.00001]; stage [ r = 0.61, P < 0.0001]). CS EPX identified subjects with active EoE (area under the curve = 0.86, P < 0.0001). DISCUSSION: The correlation of CS EPX with eosinophilic inflammation and histologic disease severity supports its diagnostic utility in EoE.

High-Grade Intraventricular Astroblastoma in a Young Adult: A Rare and Controversial Tumor to Manage.

Astroblastoma is a rare primary central nervous system tumor of controversial site of origin. They account for 0.45-2.8% of all primary neuroepithelial central nervous system. It has been reported in paediatric age group with bimodal age distribution affecting more females with male to female ratio being 1:11. Astroblastomas are controversial and challenging tumors in terms of diagnosis and therapeutics. Since it carries an unpredictable disease course it needs a regular follow up even for low grade tumor. Authors have tried various schedules of post op radiotherapy after maximum safe resection. Various chemotherapeutic drugs combination have also been tried without much success. We here report a 35 years old female patient who was diagnosed with high grade astroblastoma referred for post-operative radiotherapy after gross total resection. Since it is extremely rare tumor, its treatment still not well defined and also makes it difficult conduct studies to examine tumor characteristics.

High-Quality Genome Reconstruction of Candida albicans CHN1 Using Nanopore and Illumina Sequencing and Hybrid Assembly.

We report an improved, nearly closed, high-quality draft genome reconstruction of the Candida albicans CHN1 strain (ATCC MYA-4779), a human isolate, using Illumina and Nanopore sequencing. Covering six complete and two partial nuclear chromosomes along with a partial mitochondrial genome, this assembly is 14,787,852 bases in size, with 5,935 genes.

Diagnosis of Pediatric Non-Esophageal Eosinophilic Gastrointestinal Disorders by Eosinophil Peroxidase Immunohistochemistry.

BACKGROUND: Diagnosis of non-esophageal eosinophilic gastrointestinal disorders requires quantification of tissue eosinophils. Our objective was to evaluate eosinophil peroxidase (EPX) immunohistochemistry (IHC) as a method for histologic diagnosis of eosinophilic gastritis (EG) and eosinophilic duodenitis (EoD). METHODS: We performed a retrospective analysis of biopsies from pediatric EG/EoD cases and controls. Subjects with EG or EoD had ≥30 eosinophils per high power field (eos/hpf) in ≥5 hpf in the stomach and/or ≥3 hpf in the duodenum, respectively. Controls had no histopathologic diagnosis recorded. Tissue eosinophil counts were assessed by hematoxylin & eosin stains. EPX stains were assessed using a unique histopathologic scoring system. Slides were digitized and EPX+ staining area/mm2 was quantified by image analysis. RESULTS: Twenty-six EG/EoD cases and 40 controls were analyzed. EPX scores and EPX/mm2 levels were markedly elevated in EG/EoD (p ≤ 0.0001). Eosinophil density (eos/mm2) correlated strongly with EPX scores and EPX/mm2 levels in the stomach (r ≥ 0.77) and moderately with EPX scores and EPX/mm2 levels in the duodenum (r ≥ 0.52); (p < 0.0001). EPX quantification identified EG/EoD subjects with high diagnostic accuracy (EPX score: AUC = 1 for EG and EoD; EPX/mm2: AUC = 0.98 (95%CI 0.96-1) for EG, AUC = 0.91 (95%CI 0.81-1) for EoD). CONCLUSION: EPX-based assessment of eosinophilic inflammation may facilitate automated histologic diagnosis.

Synthesis, structures and catalytic activity of some BINOL based boronates and boronium salts.

The BINOL supported chiral boronate ester [C10H12O2BC6F5(THF)] [(R)-1], [C10H12O2BC6F5(O[double bond, length as m-dash]PEt3)] [(R)-3] and [C10H12O2BC6F5]2 [(R,R)-2] as well as the chiral boronium salts [C10H12O2B(O[double bond, length as m-dash]PEt3)2]+[B(O2C10H12)2]-, [(R)-6] and [C10H12O2B(O[double bond, length as m-dash]SMe2)2]+[B(O2C10H12)2]- [(R)-7] have been synthesized, characterized by NMR spectroscopy, and the solid state structures of [(R)-1], [(R,R)-2] and [(R)-3] determined. Chiral ester [(R)-1] was found to be a potent Lewis acid, similar to B(C6F5)3, and capable of rapidly catalyzing the annulation of (R)-, (S)- and rac-styrene oxide with nitrone PhCH[double bond, length as m-dash]N(O)Me to trans-2-methyl-3,6-diphenyl-1,4,2-dioxazine (trans-11) with high regio- and diastereoslectivities.

Arteritis and Large Vessel Occlusive Strokes in Children After COVID-19 Infection.

We describe 2 previously healthy children who suffered disabling arterial ischemic strokes because of acute intracranial large vessel occlusion within 3 to 4 weeks of coronavirus disease 2019 (COVID-19) infection. Both children presented from communities with high COVID-19 case rates in the Southwest United States. An 8-year-old American Indian girl experienced severe iron deficiency anemia requiring blood transfusion and presented with bilateral middle cerebral artery (MCA) distribution strokes 3 weeks later. She underwent emergent mechanical thrombectomy of the left MCA with successful clot retrieval but experienced reocclusion of that artery 5 hours after intervention. She also had evidence of cerebral arteritis on catheter angiography and vessel wall imaging, and clot pathology revealed recently formed, unorganized platelet- and fibrin-rich thrombus with sparse clusters of erythrocytes, degenerated histiocytes, few eosinophils, and rare neutrophils. A 16-year old African American boy demonstrated evidence of arteritis on brain magnetic resonance angiography and serological markers of cardiac and renal injury accompanied by positive lupus anticoagulant antibodies. The children described in this report express clinical features inconsistent with focal cerebral arteriopathy, including elevated markers of systemic inflammation in both bilateral MCA strokes in one case and multiple organ system dysfunction in the other case. Neither patient fulfilled criteria for multisystem inflammatory syndrome in children, given absence of fever. These cases illustrate that systemic postinfectious arteritis with cerebrovascular involvement may complicate COVID-19 infection in previously healthy school-aged children, and their presentations may overlap but not fulfill criteria for multisystem inflammatory syndrome in children or focal cerebral arteriopathy.

STMN1 is Overexpressed in Adrenocortical Carcinoma and Promotes a More Aggressive Phenotype In Vitro.

BACKGROUND: Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with a poor prognosis and few therapeutic options. Stathmin1 (STMN1) is a cytosolic protein involved in microtubule dynamics through inhibition of tubulin polymerization and promotion of microtubule depolymerization, which has been implicated in carcinogenesis and aggressive behavior in multiple epithelial malignancies. We aimed to evaluate expression of STMN1 in ACC and to elucidate how this may contribute to its malignant phenotype. METHODS: STMN1 was identified by RNA sequencing as a highly differentially expressed gene in human ACC samples compared with benign adrenal tumors. Expression was confirmed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR), Western blot, and immunohistochemical (IHC) staining of a tissue microarray (TMA) from two independent cohorts. The biologic relevance of STMN1 was investigated in NCI-H295R cells by lentivirus-mediated silencing. RESULTS: Differential gene expression demonstrated an eightfold increase in STMN1 messenger RNA (mRNA) in malignant compared with benign adrenal tissue. IHC showed significantly higher expression of STMN1 protein in ACC compared with normal and benign tissues. STMN1 knockdown in an ACC cell line resulted in decreased cell viability, cell-cycle arrest at G0/G1, and increased apoptosis in serum-starved conditions compared with scramble short hairpin RNA (shRNA) controls. STMN1 knockdown also decreased migration, invasion, and anchorage-independent growth compared with controls. CONCLUSIONS: STMN1 is overexpressed in human ACC samples, and knockdown of this target in vitro resulted in a less aggressive phenotype of ACC, particularly under serum-starved conditions. Further study is needed to investigate the feasibility of interfering with STMN1 as a potential therapeutic target.

Genetic evaluation of ex situ conservation breeding projects of Cheer Pheasant (Catreus wallichii) and Western Tragopan (Tragopan melanocephalus) in India.

When setting-up a captive population, genetic assessment of founders is essential to formulate effective breeding strategies that minimize the negative effects of inbreeding in the successive generations caused by mating between genetically related individuals. We carried out molecular genetic analysis of Cheer Pheasant and Western Tragopan populations of Chail and Sarahan Pheasantries in the State of Himachal Pradesh. The results revealed that the captive stock of Cheer Pheasant is sustaining well and does not exhibit signatures of inbreeding. Conversely, inbreeding is strongly evident in Western Tragopan population. Our study adds new dimensions to the captive management of Cheer Pheasant and Western Tragopan populations and contradicts with a previous study conducted on the same Western Tragopan population of Sarahan Pheasantry using studbook data. This study demonstrates strong evidence for retaining genetic assessment as an integral part to formulate policies/strategies for conservation breeding projects and proposes refining existing studbook records by incorporating microsatellites data and genetic analyses. Zoo Biol. 35:269-273, 2016. © 2016 Wiley Periodicals, Inc.

Recurrent pyometra and xanthogranulomatous salpingitis: A rare pathologic association in a postmenopausal lady.

Xanthogranulomatous inflammation is a rare, non-neoplastic variant of chronic inflammation. Of the 15 reported cases of Xanthogranulomatous endometritis, majority (60%) were accompanied by endometrial carcinoma. We herein report a case of a postmenopausal woman presenting with recurrent pyometra who was suspected to be case of cervical tuberculosis and treated for the same. Inspite of antitubercular therapy, she had cervical stenosis and developed recurrent pyometra over the next 2 years requiring repeated drainage. She then underwent hysterectomy and was found to have co-existent Xanthogranulomatous salpingitis (XGS) on histopathological examination. Xanthogranulomatous inflammation is a rare pathological diagnosis that gynecologists need to be aware of while managing such patients.

In Vitro antifungal potency of plant extracts against five phytopathogens

The antifungal activity of aqueous extract of Cannabis sativa, Parthenium hysterophorus, Urtica dioeca, Polystichum squarrosum and Adiantum venustum was investigated against Alternaria solani, Alternaria zinniae, Curvularia lunata, Rhizoctonia solani and Fusarium oxysporum at different concentrations (5, 10, 15 and 20 percent). At 20 percent, maximum antifungal potential was observed with the extracts of C. sativa, which recorded excellent inhibitory activity against C. lunata (100 percent), A. zinniae (59.68 percent), followed by leaf extract of P. hysterophorus (50 percent) against A. solani. The application of botanical extracts for disease management could be less expensive, easily available, non-polluting and eco-friendly.

Phosphorus availability to maize as influenced by organic manures and fertilizer P associated phosphatase activity in soils.

Laboratory incubation and green house studies were conducted to compare the P availability of organic manures and P uptake from organic manures by maize. Various organic manures viz. Poultry manure (PM), Farmyard manure (FYM), Green manure (GM) and Crop residue (CR) and graded levels of fertilizer P were applied in Samana sandy loam and Ladhowal silt loam soils and incubated for 7, 15, 30, 60 and 90 days. Samples were analyzed for P availability, P uptake and alkaline phosphatase activity. The overall, phosphatase activity, Paranitrophenyl phosphate (PNP h(-1)g(-1)), in the Ladhowal silt loam soil was higher than in the Samana sandy loam soil. As the level of inorganic P increased, the release of PNP h(-1)g(-1) soil also increased. Among different organic manures, PM registered the highest enzyme activity followed by FYM, GM and CR. Compared to 7 days incubation a slightly higher increase in PNP was noticed in samples from 90 days incubation in both soils. The differential phosphatase activity in the organic manures was further reflected in dynamic P availability. The highest amount of Olsen extractable P was in PM-treated soil followed by FYM, GM and field pea crop residue. Organic manure addition along with inorganic P, irrespective of the source, increased the Olsen extractable P throughout the incubation period. Total P uptake by maize increased with the increasing level of inorganic P in both soils. The highest uptake was obtained in PM-treated soil and lowest in the CR-amended soil. We conclude that PM more readily supplies P to plants than other organic manure sources.

Toxicological investigations on the methanol sub-fraction of the seeds of Carica papaya as a male contraceptive in albino rats.

Pre-clinical acute and sub-chronic toxicity studies of the methanol sub-fraction (MSF) of the seeds of Carica papaya, a putative male contraceptive, have been investigated in rats to evaluate safety of the test substance. A single oral dose of MSF at 2000 mg/kg body weight was studied over 14 days for acute toxicity, and daily oral doses of 50, 100, 250 and 500 mg/kg body weight were studied for 28- and 90-day periods for sub-chronic toxicity. Body weight, food and water intake and phenotypical toxicological symptoms were recorded daily. Sperm analysis, hematology, serum clinical biochemistry, libido and pathological examination of vital organs were recorded at the termination of the experimental periods. We observed no overt general toxicity in exposed animals. Food and water intake showed daily fluctuations within control limits. Sperm density showed a significant decrease in all 28- and 90-day repeated dose treated animals whereas total sperm motility inhibition was observed at 250 and 500 mg/kg dose levels at the 28-day time interval but in all dose groups at the 90-day interval. The preliminary results suggest the test substance may be a safe approach to male anti-fertility.

Perspectives of contraceptive choices for men.

Apart from condoms and vasectomy, which have several limitations of their own, no other methods of contraception are available to men. Various chemical, hormonal, vas based and herbal contraceptives have been examined and few of them have reached the stage of clinical testing. Promising leads have been obtained from testosterone buciclate/undecanoate, alone or in combination with levonorgestrel butanoate or cyproterone acetate, RISUG, an injectable intravasal contraceptive and a few herbal products, particularly the seed products of Carica papaya. It is feasible that an ideal male contraceptive, that meets out all the essential criteria will be made available to the community in the near future.