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Many drugs were recommended as antiviral agents for infection control and effective therapy to reduce the mortality rate for COVID-19 patients. Hydroxychloroquine (HCQ), an antimalarial drug, has been controversially recommended for prophylactic use in many countries, including India, to control SARS-CoV-2 infections. We have explored the effect of prophylactic HCQ from the cells of bronchoalveolar lavage fluids from COVID-19-induced acute respiratory distress syndrome patients to determine the level of infection and ultrastructural alterations in the ciliated epithelium, type II pneumocytes, alveolar macrophages, neutrophils, and enucleated granulocytes. Ultrastructural investigation of ciliated epithelium and type II pneumocytes showed lesser infections and cellular impairment in the prophylactic HCQ+ group than HCQ− group. However, macrophages and neutrophils displayed similar infection and ultrastructural alterations in both patient groups. The enucleated fragments of granulocytes showed phagocytosis of the matured virus in HCQ+ groups. The present report unveils the ultrastructural proof to complement the paradox regarding the role of prophylactic HCQ in COVID-19 patients. [ABSTRACT FROM AUTHOR]

Benign fibro-osseous lesions (BFOLs) are a diverse group of lesions showing considerable degree of overlap with low grade osteosarcoma (LGOS). Further, de-differentiated osteosarcoma (DOS) is usually indistinguishable from conventional high-grade OS (COS) if LGOS foci are not identified. Thus, there is a need for adjunctive immunohistochemical markers to differentiate OS from benign FOLs as well as DOS from COS. This study evaluated the role of immunohistochemical expression of MDM2, CDK4, parafibromin, BCL-2 and Galectin-1 (Gal-1) in accurate characterization of benign FOLs and in differentiating them from OS. From our archives, we retrieved 101 tissue samples which were diagnosed as osteosarcoma (OS) /ossifying fibroma (OF) / fibrous dysplasia (FD) or fibrous hyperplasia (FH) and examined their immunohistochemical staining pattern with the aforementioned antibodies. MDM2 showed 100% specificity for diagnosing OS. CDK4 and Gal-1 showed linear increase in immunoexpression from benign BFOLs to OS. BCL-2 showed equivocal immunopositivity in OF and OS, but the positivity was higher than that observed in FD. The highest immunoexpression for parafibromin was seen in FD followed by OF and OS cases. Thus, MDM2 is most specific, and Gal-1 is most sensitive of all the markers studied in differentiating OS from benign mimics. Combination of these two markers can be used as an adjunct to conventional imaging and microscopy in accurate characterization of these lesions. Further MDM2 overexpression can differentiate DOS and COS. [ABSTRACT FROM AUTHOR]

Angiotensin-converting enzyme 2 (ACE2) is a key host protein by which severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) enters and multiplies within cells. The level of ACE2 expression in the lung is hypothesised to correlate with an increased risk of severe infection and complications in COrona VIrus Disease 2019 (COVID-19). To test this hypothesis, we compared the protein expression status of ACE2 by immunohistochemistry (IHC) in post-mortem lung samples of patients who died of severe COVID-19 and lung samples obtained from non-COVID-19 patients for other indications. IHC for CD61 and CD163 was performed for the assessment of platelet-rich microthrombi and macrophages, respectively. IHC for SARS-CoV-2 viral antigen was also performed. In a total of 55, 44 COVID-19 post-mortem lung samples were tested for ACE2, 36 for CD163, and 26 for CD61, compared to 15 non-covid 19 control lung sections. Quantification of immunostaining, random sampling, and correlation analysis were used to substantiate the morphologic findings. Our results show that ACE2 protein expression was significantly higher in COVID-19 post-mortem lung tissues than in controls, regardless of sample size. Histomorphology in COVID-19 lungs showed diffuse alveolar damage (DAD), acute bronchopneumonia, and acute lung injury with SARS-CoV-2 viral protein detected in a subset of cases. ACE2 expression levels were positively correlated with increased expression levels of CD61 and CD163. In conclusion, our results show significantly higher ACE2 protein expression in severe COVID-19 disease, correlating with increased macrophage infiltration and microthrombi, suggesting a pathobiological role in disease severity. [ABSTRACT FROM AUTHOR]

Pre-eclampsia (PE) is a pregnancy-specific disorder, characterized by hypertension and proteinuria. In PE, trophoblasts mediated inadequate remodeling of uterine spiral arteries seem to interrupt uteroplacental blood flow, one of the hallmarks in the early onset of PE (EO-PE). This, in turn, results in placental ischemia–reperfusion injury during hypoxia and reoxygenation episodes, leading to the generation of reactive oxygen species (ROS) and oxidative stress (OS). But still it is debatable if OS is a cause or consequence of PE. In this present study, we have investigated the effects of OS on PE placentae and trophoblast cell functions using BeWo and HTR8/SVneo cell lines. PE placental tissues showed abnormal ultrastructure, high level of reactive oxygen species (ROS) with altered unfolded protein responses (UPR) in compare with term placental tissues. Similar to PE placentae, during OS induction, the trophoblast cells showed altered invasion and migration properties with significantly variable expression of differentiation and invasion markers, e.g., syncytin and MMPs. The effect was rescued by antioxidant, N-acetyl cysteine, thereby implying a ROS-specific effect and in the trophoblast cells, OS triggers UPR pathway through IRE1α-XBP1 axis. Taken together, these findings highlight the harmful effect of unfolded protein response, which was induced due to OS on trophoblast cells and deformed invasion and differentiation programme and can be extended further to clinical settings to identify clinically approved antioxidants during pregnancy as a therapeutic measure to reduce the onset of PE. [ABSTRACT FROM AUTHOR]

The strength between the cortical screw and bone following an orthopaedic implant surgery is an important determinant for the success of osteosynthesis. An excessive axial cutting force during drilling produces microcracks in the bone surface, resulting in reduced strength between the screw and bone, resulting in loosening of implant. The present work, investigates the influence of drilling parameters on microcracks generated in the drilled surface and pull-out strength of screw fixed in cortical bone of human tibia. The holes were drilled by two different techniques: conventional surgical bone drilling (CSBD) and rotary ultrasonic bone drilling (RUBD), by a recently developed operation theatre (OT) compatible machine. Cutting force generated in drilling of human tibia using RUBD was 30–40% lesser than that of CSBD. Scanning electron microscopy (SEM) also revealed that RUBD produced significantly lesser and thinner microcracks than that of CSBD in human bones. Biomechanical pull-out test results showed that, the pull-out strength of screws inserted into drilled holes by RUBD was much higher (100–150%) than that of CSBD. A significant difference in pull-out strength (p < 0.05) between RUBD and CSBD was revealed by statistical analysis at 95% confidence interval. [ABSTRACT FROM AUTHOR]

The purpose of the study was to determine the phases of the menstrual cycle in the reproductive age group of females who committed suicide as compared with a control group of females who died from causes other than suicide. The study included 86 cases in the suicidal group and 80 cases in the non-suicidal group. The menstrual phase was decided by the gross and histological examination of the uterus and ovary at autopsy. Deaths were more common during the secretory phase (56.9%) in the suicidal group, while in the non-suicidal group, death occurred more commonly in the proliferative phase (66.3%). In reference to proliferative phase, deaths were more in the secretory phase and menstrual phase in the suicidal group, adjusted odd's ratio (OR) being 3.7 (p = 0.042) and 4.7 (p = 0.032), respectively. Corpus luteum was present in the right ovary of 43 and 14 victims of suicidal and non-suicidal deaths, respectively, while it was in the left ovary of 3 and 11 victims of suicidal and non-suicidal death, respectively. Odd's ratio was 10.3 for corpus luteum to be in the right ovary in comparison with the left ovary for the suicidal group (p = 0.001). This study revealed that suicidal chances in a woman are significantly more in the menstrual phase and the secretory phase of the menstrual cycle. The presence of corpus luteum in the right ovary is associated with an increased risk of suicide, but the reason is not known. [ABSTRACT FROM AUTHOR]

Myoepitheliomas (MEs) are uncommon tumours of the soft tissue with an intermediate biological behaviour and uncertain differentiation. Primary intra-osseous MEs are rare and occur predominantly in the axial and proximal appendicular skeleton in middle-aged patients. The morphological variation of the tumour cells and stromal metaplasia may cause considerable diagnostic confusion, especially when it occurs in an unusual location. A wide panel of immunohistochemical markers is required to exclude other histological mimics. A 37-year-old male presented with a recurrent swelling in the right middle finger for 1-month duration. Radiographic images showed an expansile, lytic, intra-osseous lesion with high signal intensity on T2W fat-suppressed MR images in the proximal phalanx of the right middle finger without cortical breach, highly suggestive of an enchondroma. Histopathology revealed a lobulated tumour comprising of polygonal to spindle cells in groups and cords in a chondromyxoid stroma. No cellular atypia was noted. The tumour cells were immunopositive for epithelial membrane antigen (EMA), p63, S100 and smooth muscle actin (SMA), compatible with the diagnosis of an intraosseous ME. The proximal phalanx of the right middle finger was excised, revealing a similar tumour, and the patient has been on regular follow-up for the last 18 months without any recurrence. Primary intra-osseous MEs are extremely rare, and this is the second reported occurrence in small bones. A differential diagnosis of ME should be kept for enchondroma-like lesions of the bone for proper histopathological assessment and accurate diagnosis. Documentation of such cases and follow-up will enhance our understanding of their clinical course and prognosis. [ABSTRACT FROM AUTHOR]