IGg4-related Disease Presenting as Rapidly Progressive Renal Failure and Inguinal Iymphadenopathy.

A 58-year-old man presented with swelling in the left inguinal region and loss of appetite, nausea and azotemia with a serum creatinine of 5.2 mg/dL and urine albumin of 1+ and normal size kidneys with no hematuria. His serum creatinine increased to 9 mg/dL over 1 month, his total proteins were 10.8 and serum albumin was 3.3 g/dL, and lymph node excision biopsy showed fragments of lymphoid tissue with interfollicular areas containing sheets of plasma cells and atretic germinal centers. In view of unexplained renal failure, he underwent renal biopsy, which showed interstitial inflammatory infiltrate composed of lymphocytes and rich in plasma cells with storiform fibrosis and a possibility of IgG4-related renal disease was reported. On further evaluation, serum electrophoresis showed no M band. Serum IgG4 levels were 18.2 g/L (0.03-2 g/L). A diagnosis of IgG4-related renal disease was confirmed.

Whole slide imaging: The futurescape of histopathology.

The last two decades have seen considerable progress in the use of digital technology in histopathology. Digital photography of microscopic slides and the use of static images gave way to robotic microscopes. These technologies had their own limitations that precluded their widespread use. Creation of whole slide scanners that can produce digitized whole slide images (WSI) and the "comparable to conventional microscope" experience opened multiple avenues for their utilization not only in specific applications such as expert consults, quality assessment programs, education and archiving, but also for routine day-to-day reporting. Industry pressures driven by consumer requirements have led to great development in image quality, speed of scanning, size of stored files, and capital cost of scanners. User-friendly software and analytical algorithms have further enhanced user experience. Challenges that need to be either accepted or overcome would include capital expense not significantly yielding a return on investment, and management of storage space. This review attempts to take the reader through the evolution of WSI scanners and to share the author's experience with WSI for routine histopathology reporting, education, and external quality assessment along with a review of available literature.

H I 21-centimetre emission from an ensemble of galaxies at an average redshift of one.

Baryonic processes in galaxy evolution include the infall of gas onto galaxies to form neutral atomic hydrogen, which is then converted to the molecular state (H2), and, finally, the conversion of H2 to stars. Understanding galaxy evolution thus requires an understanding of the evolution of stars and of neutral atomic and molecular hydrogen. For the stars, the cosmic star-formation rate density is known to peak at redshifts from 1 to 3, and to decline by an order of magnitude over approximately the subsequent 10 billion years1; the causes of this decline are not known. For the gas, the weakness of the hyperfine transition of H I at 21-centimetre wavelength-the main tracer of the H I content of galaxies-means that it has not hitherto been possible to measure the atomic gas mass of galaxies at redshifts higher than about 0.4; this is a critical gap in our understanding of galaxy evolution. Here we report a measurement of the average H I mass of star-forming galaxies at a redshift of about one, obtained by stacking2 their individual H I 21-centimetre emission signals. We obtain an average H I mass similar to the average stellar mass of the sample. We also estimate the average star-formation rate of the same galaxies from the 1.4-gigahertz radio continuum, and find that the H I mass can fuel the observed star-formation rates for only 1 to 2 billion years in the absence of fresh gas infall. This suggests that gas accretion onto galaxies at redshifts of less than one may have been insufficient to sustain high star-formation rates in star-forming galaxies. This is likely to be the cause of the decline in the cosmic star-formation rate density at redshifts below one.

Guidelines for various laboratory sections in view of COVID-19: Recommendations from the Indian Association of Pathologists and Microbiologists.

Declared as a pandemic by WHO on March 11, 2020, COVID-19 has brought about a dramatic change in the working of different laboratories across the country. Diagnostic laboratories testing different types of samples play a vital role in the treatment management. Irrespective of their size, each laboratory has to follow strict biosafety guidelines. Different sections of the laboratory receive samples that are variably infectious. Each sample needs to undergo a proper and well-designed processing system so that the personnel involved are not infected and also their close contacts. It takes a huge effort so as to limit the risk of exposure of the working staff during the collection, processing, reporting or dispatching of biohazard samples. Guidelines help in preventing the laboratory staff and healthcare workers from contracting the disease which has a known human to human route of transmission and high rate of mortality. A well-knit approach is the need of the hour to combat this fast spreading disease. We anticipate that the guidelines described in this article will be useful for continuing safe work practices by all the laboratories in the country.

Pulmonary alveolar proteinosis in children: An unusual presentation with significant clinical impact.

Pulmonary alveolar proteinosis (PAP) - an unusual diffuse lung disease characterized by alveolar accumulation of phospholipoprotein material, with a peak incidence in third to fourth decade and male predominance is also described in children. Recorded prevalence is 0.1/100,000 individuals. Major clinicopathogenetic subtypes include autoimmune (idiopathic) associated with granulocyte-macrophage colony-stimulating factor autoantibodies, secondary form, and the congenital form (associated with surfactant gene mutations). Common presenting features include dyspnea, cough, low-grade fever, inspiratory crackles, and digital clubbing. Pulmonary function shows a restrictive ventilatory defect. X-rays show bilateral patchy to extensive consolidations, and bronchial lavage yields a milky fluid. Characteristic microscopic findings on lung biopsy include filling of terminal bronchioles and alveolar spaces by deep pink granular PAS-positive material. Whole lung lavage is the safest and most effective form of treatment. We present brief profiles of two young children identified as having PAP, along with follow-up data on one of them.

Stringent Constraints on Fundamental Constant Evolution Using Conjugate 18 cm Satellite OH Lines.

We have used the Arecibo Telescope to carry out one of the deepest-ever integrations in radio astronomy, targeting the redshifted conjugate satellite OH 18 cm lines at z≈0.247 towards PKS 1413+135. The satellite OH 1720 and 1612 MHz lines are, respectively, in emission and absorption, with exactly the same line shapes due to population inversion in the OH ground state levels. Since the 1720 and 1612 MHz line rest frequencies have different dependences on the fine structure constant α and the proton-electron mass ratio µ, a comparison between their measured redshifts allows one to probe changes in α and µ with cosmological time. In the case of conjugate satellite OH 18 cm lines, the predicted perfect cancellation of the sum of the line optical depths provides a strong test for the presence of systematic effects that might limit their use in probing fundamental constant evolution. A nonparametric analysis of our new Arecibo data yields [ΔX/X]=(+0.97±1.52)×10^{-6}, where X≡µα^{2}. Combining this with our earlier results from the Arecibo Telescope and the Westerbork Synthesis Radio Telescope, we obtain [ΔX/X]=(-1.0±1.3)×10^{-6}, consistent with no changes in the quantity µα^{2} over the last 2.9 Gyr. This is the most stringent present constraint on fractional changes in µα^{2} from astronomical spectroscopy, and with no evidence for systematic effects.

Diagnostic potential of monoclonal antibodies against the capsid protein of chikungunya virus for detection of recent infection.

Chikungunya fever is self-limiting. However, neurological and hemorrhagic complications have been seen in recent outbreaks. The clinical manifestations of this disease are similar to those of dengue virus infection, indicating the need for differential diagnosis in areas such as India, which are endemic for both viruses. The aim of the present study was to develop monoclonal antibodies (MAbs) against Chikungunya virus (CHIKV) and assess their use in MAb-based IgM capture ELISA (MAC ELISA). The ELISA detects CHIKV-specific IgM antibodies, a marker of recent infection, in a patient's serum. One IgG1 and two IgM isotype hybrids were obtained. All of the subclones derived from the IgG1 hybrid recognized the C protein of CHIKV. The anti-C MAb ClVE4/D9 was the most promising as a detector antibody in MAC ELISA (C-MAb ELISA) yielding higher positive-to-negative (P/N) ratios. When compared with the CHIKV MAC ELISA kit developed by the National Institute of Virology (NIV), Pune (NIV MAC ELISA), the sensitivity of the test was 87.01 % with 100 % specificity. The positive and negative predictive values (PPV and NPV) were 100 % and 94.47 %, respectively. In precision testing, standard deviation (SD) and coefficient of variation (% CV) values of the C-MAb ELISA were within acceptable limits. The C-MAb ELISA detected anti-CHIKV IgM in serum of patients up to five months after the onset of infection, indicating that anti-C MAbs have strong potential for use in MAC ELISA to detect recent CHIKV infection.

Effect of yoga therapy on plasma oxytocin and facial emotion recognition deficits in patients of schizophrenia.

CONTEXT: Yoga therapy has been demonstrated to be useful in treatment of negative symptoms and improving the socio-occupational functioning and emotion recognition deficits in antipsychotic-stabilized schizophrenia patients. Oxytocin has been recently implicated in social cognition deficits in schizophrenia. The effect of yoga therapy on oxytocin levels in schizophrenia has not been studied. AIMS: This study aimed to assess the effect of yoga therapy on symptoms, socio-occupational functioning, facial emotion recognition deficits and plasma oxytocin levels in antipsychotic stabilized schizophrenia patients. SETTINGS AND DESIGN: Randomized controlled study on 43 consenting, medication stabilized patients with schizophrenia in a tertiary psychiatric center using yoga intervention and waitlisted groups. MATERIALS AND METHODS: A total of 43 schizophrenia patients were randomized to yoga group (n=15) or waitlist group (n=28). Patients in the yoga group received training in a specific yoga therapy module for schizophrenia. Patients in both groups were continued on stable antipsychotic medication. Assessments included scale for assessment of positive symptoms, scale for assessment of negative symptoms, socio-occupational functioning scale and tool for recognition of emotions in neuropsychiatric disorders (TRENDS) and plasma oxytocin levels; performed at baseline and at the end of 1 month. RESULTS: A total of 15 patients in the yoga group and 12 in waitlist group completed the study. The yoga therapy group showed a significant improvement in socio-occupational functioning, performance on TRENDS (P<0.001) and plasma increase in oxytocin levels (P=0.01) as compared with the waitlist group. CONCLUSION: The study supported the role of add-on yoga therapy in management of schizophrenia and demonstrated an improvement in endogenous plasma oxytocin levels in schizophrenia patients receiving yoga therapy.

Nicotinamide mononucleotide adenylyltransferase2 overexpression enhances colorectal cancer cell-kill by Tiazofurin.

Colorectal cancer cells exhibit limited cytotoxicity towards Tiazofurin, a pro-drug metabolized by cytosolic nicotinamide mononucleotide adenylyltransferase2 (NMNAT2) to thiazole-4-carboxamide adenine dinucleotide, a potent inhibitor of inosine 5'-monophosphate dehydrogenase required for cellular guanylate synthesis. We tested the hypothesis that colorectal cancer cells that exhibit low levels of NMNAT2 and are refractory to Tiazofurin can be rendered sensitive to Tiazofurin by overexpressing NMNAT2. Transfection of hNMNAT2 resulted in a six- and threefold cytoplasmic overexpression in Caco2 and HT29 cell lines correlating with Tiazofurin-induced enhanced cell-kill. Folate receptors expressed on the cell surface of 30-50% colorectal carcinomas were exploited for cellular targeting with Tiazofurin encapsulated in folate-tethered nanoparticles. Our results indicated that in wild-type colorectal cancer cells, free Tiazofurin-induced EC50 cell-kill was 1500-2000 µM, which was reduced to 66-156 µM in hNMNAT2-overexpressed cells treated with Tiazofurin encapsulated in non-targeted nanoparticles. This efficacy was improved threefold by encapsulating Tiazofurin in folate-tethered nanoparticles to obtain an EC(50) cell-kill of 22-59 µM, an equivalent of 100-300 mg m(-2) (one-tenth of the approved dose of Tiazofurin in humans), which will result in minimal toxicity leading to cancer cell-kill. This proof-of-principle study suggests that resistance of colorectal cancer cell-kill to Tiazofurin can be overcome by sequentially overexpressing hNMNAT2 and then facilitating the uptake of Tiazofurin by folate-tethered nanoparticles, which enter cells via folate receptors.

Quality control in the histopathology laboratory: an overview with stress on the need for a structured national external quality assessment scheme.

The concept of quality control in histopathology is relatively young and less well understood. Like in other disciplines of laboratory medicine, the concept of quality and its control is applicable to pre analytical, analytical and post analytical activities. Assessment of both precision and accuracy performances is possible by appropriate internal and external quality control and assessment schemes. This article is a review of all processes that achieve quality reporting in histopathology. There is a special focus on external quality assessment - a scheme that lacks organization on a national level in our country. Statistical data derived from a small scale external quality assurance program is also analyzed along with recommendations to organize an effective national scheme with the participation of authorized zonal centers.

Expression of human chorionic gonadotropin beta in gastric carcinoma: A retrospective immunohistochemical study.

CONTEXT: Beta Human Chorionic Gonadotropin (ßHCG), a marker of the trophoblastic neoplasm, is also secreted by non-trophoblastic neoplasms including gastric carcinomas. Its role in disease progression remains unclear. AIM: To investigate the incidence of ßHCG positivity in gastric carcinomas and correlate its presence with the biological behavior of the tumor. SETTING AND DESIGN: A hospital-based, immunohistochemical study. MATERIALS AND METHODS: One hundred and fifty formalin-fixed, paraffin-embedded tissue specimens from histopathologically confirmed cases of gastric carcinoma were immunostained using an indigenously developed antibody against ßHCG. Tumors with diffuse reactivity to ßHCG were considered as positive. Those with occasional, focal or no reactivity to ßHCG were considered as negative. STATISTICAL ANALYSIS: Differences in ßHCG staining were compared according to the histological grade and surgical stage using the χ(2) test. Using the Cox proportional hazards model, the time till the onset of development of an adverse outcome after surgery (defined as death, local or distant metastasis) was compared between the bHCG positive and negative tumors. RESULTS: Twenty-eight (18.7%) of the 150 specimens were ßHCG positive. No association was found between the histological grade (P=0.49) and the surgical stage (P=0.19) with ßHCG positivity. The median disease-free survival after surgery was not different among ßHCG positive and negative tumors. Risk of an adverse outcome after surgery was significantly associated with the stage of the tumor (Hazard ratio=2.9, 95% confidence interval: 1.1-7.4). No association was observed with grade or ßHCG positivity. CONCLUSION: ßHCG immunoreactivity was observed in about one-fifth of the gastric cancers. ßHCG reactivity, however, played no role in the biological behavior.

Post transplant thrombotic microangiopathy causing acute renal failure.

Acute Renal Failure (ARF) in the immediate post transplant period is most commonly due to acute tubular necrosis, acute cellular rejection and calcineurin inhibitor toxicity apart from usual prerenal and post renal causes. In this report, we discuss an interesting and unusual cause of ARF due to thrombotic micro angiopathy in the immediate post transplant setting.

Conjugate 18 cm OH satellite lines at a cosmological distance.

We have detected the two 18 cm OH satellite lines from the z approximately 0.247 source PKS1413+135, the 1720 MHz line in emission and the 1612 MHz line in absorption. The 1720 MHz luminosity is L(OH) approximately 354L (center dot in circle), more than an order of magnitude larger than that of any other known 1720 MHz maser. The profiles of the two satellite lines are conjugate, implying that they arise in the same gas. This allows us to test for any changes in the values of fundamental constants without being affected by systematic uncertainties arising from relative motions between the gas clouds in which the different lines arise. Our data constrain changes in G identical with g(p)[alpha(2)/y](1.849), where y identical with m(e)/m(p); we find DeltaG/G=2.2+/-3.8 x 10(-5), consistent with no changes in alpha, g(p), and y.

Constraining the variation of fundamental constants using 18 cm OH lines.

We describe a new technique to estimate variations in the fundamental constants using 18 cm OH absorption lines, with the advantage that all lines arise in the same species, allowing a clean comparison between the measured redshifts. In conjunction with one additional transition, it is possible to simultaneously measure changes in alpha, g(p), and y identical with m(e)/m(p). We use the 1665 and 1667 MHz line redshifts in conjunction with those of HI 21 cm and mm-wave molecular absorption in a gravitational lens at z approximately 0.68 to constrain changes in the three parameters over the redshift range 0

Telepathology in India.

Telepathology is the most recent addition to the pathologist's diagnostic tools. It is the acquisition of macroscopic and microscopic images for electronic transmission for diagnosis, consultation and/or education. With the addition of the personal computer at the pathologist's desktop, the stage has been set for one of the greatest advantages the Internet has to offer. Telepathology in India is in infancy, and we at PathoIndia (www.Pathoindia.com) have started a series of publication images from interesting cases in the form of weekly quiz. After cases are published, hundreds of pathologists from around the world are invited by e-mail to send in their diagnosis and comments. The responses to this quiz suggest that telepathology is catching on in the pathology community. Another intention of this series is to identify and select qualified international and Indian pathologists who would be willing to help colleagues from India requesting second opinions online.

Tumours and tumour-like conditions of the para-testicular region--a study of morphological features.

Twenty two patients with tumours or tumour-like conditions of the para-testicular region (PTR) were diagnosed over a 5 year period. Of these, 16 (73%) were benign with only one true neoplasm (papillary cystadenoma). The tumour-like conditions were comprised of 6 cases of adenomatous hyperplasia of epididymis, 4 cases of spermatic granuloma, 2 cases each of spermatocele and nodular-fibrous proliferation and one mesothelial cyst. Three patients with spermatic granuloma gave a history of trauma. No case of adenomatoid tumour was encountered. Six malignant neoplasms were diagnosed (27%) all of which were sarcomas. Five were primary to the PTR and one was a metastatic deposit from a primary leiomyoblastoma of the mesentery. Among the 5 primary sarcomas were 2 cases each of rhabdomyosarcoma and leiomyosarcoma, and 1 case of liposarcoma. The patient with leiomyoblastoma presented first with a measenteric mass which was followed a month later by a rapidly growing mass in the scrotum. Immunohistochemical staining (IHC) and Electron microscopy (EM) were done in this case. Intra-cytoplasmic myofilaments as well as desmosomes were observed. The patients ranged from 14 to 65 years of age and most presented with painless mass in the scrotum. Follow-up was not possible due to practical difficulties.

Langerhans cell histocytosis--a clinicopathological spectrum.

Langerhans cell Histiocytosis--a lesion characterised by proliferation of a variant of epidermal dendritic cell is one of the several syndromes in which histiocytes play a principal role in pathogenesis outside the context of inflammatory and metabolic storage disease. Seven cases were diagnosed as Langerhans cell Histiocytosis over a period of six years. The mode of diagnosis was Fine needle aspiration in 2 cases, open biopsy in four, and both biopsy and FNAC in one. The age range was from 2 months to 58 years and four of the seven patients were males. The lesion was unifocal in 3 cases (two in bone and one involving skin and soft tissue), multifocal in 3 and systemic in one. Electron microscopy was done in one case to demonstrate Birbeck granules. Immunohistochemical demonstration of S 100 protein was done in one case. The clinicopathologic spectrum of Langerhans cell Histiocytosis is brought out in this presentation of seven cases.