Role of Periductal and Ductular Epithelial Cells of the Adult Rat Pancreas in Pancreatic Hepatocyte Lineage: A Change in the Differentiation Commitment

Development of pancreatic hepatocytes in adult rats maintained on copper deficient diet containing 0.6% trien (CuDT) has been reported recently. To elucidate the histogenesis of hepatocytes a sequential study was undertaken using morphologic, histochemical, immunochemical, in situ hybridization, and Northern blot analysis. Male F-344 rats weighing 80 to 90 g were fed CuDT for 8 weeks and returned to normal rat chow. Beginning from 4 weeks of copper depletion, there was a progressive loss of acinar cells and by 8 weeks more than 90% of the acinar tissue was lost. During this period, there was an increase in the number of adipocytes in the interstitium, and in the number of interstitial and ductular cells. Morphologic observations were confirmed by immunoblot and Northern blot analysis, in which the amount of pancreatic proteins and their mRNAs decreased between 5 and 8 weeks. During this period, a progressive increase in the level of albumin mRNA was observed. In situ hybridization, performed at 7 weeks of copper deficiency, showed localization of albumin mRNA over interstitial and ductular cells. Pancreatic hepatocytes were identified immediately after the rats were returned to a normal diet and gradually increased in number. The hepatocytes occupied almost 60% of the pancreatic volume by 8 weeks. During the early recovery phase, hepatocytes were identified in ductules as well as in the interstitium. Based on these studies, it is concluded that both the ductular cells and interstitial cells, which resemble oval cells of liver, are capable of transforming into pancreatic hepatocytes and these cells may be considered stem-cell equivalent.     

Predictors of acquired lipodystrophy in juvenile-onset dermatomyositis and a gradient of severity

We describe the clinical features of 28 patients with juvenile dermatomyositis (JDM) and 1 patient with adult-onset dermatomyositis (DM), all of whom developed lipodystrophy (LD) that could be categorized into 1 of 3 phenotypes, generalized, partial, or focal, based on the pattern of fat loss distribution. LD onset was often delayed, beginning a median of 4.6 years after diagnosis of DM. Calcinosis, muscle atrophy, joint contractures, and facial rash were DM disease features found to be associated with LD. Panniculitis was associated with focal lipoatrophy while the anti-p155 autoantibody, a newly described myositis-associated autoantibody, was more associated with generalized LD. Specific LD features such as acanthosis nigricans, hirsutism, fat redistribution, and steatosis/nonalcoholic steatohepatitis were frequent in patients with LD, in a gradient of frequency and severity among the 3 sub-phenotypes. Metabolic studies frequently revealed insulin resistance and hypertriglyceridemia in patients with generalized and partial LD. Regional fat loss from the thighs, with relative sparing of fat loss from the medial thighs, was more frequent in generalized than in partial LD and absent from DM patients without LD. Cytokine polymorphisms, the C3 nephritic factor, insulin receptor antibodies, and lamin mutations did not appear to play a pathogenic role in the development of LD in our patients. LD is an under-recognized sequela of JDM, and certain DM patients with a severe, prolonged clinical course and a high frequency of calcinosis appear to be at greater risk for the development of this complication. High-risk JDM patients should be screened for metabolic abnormalities, which are common in generalized and partial LD and result in much of the LD-associated morbidity. Further study is warranted to investigate the pathogenesis of acquired LD in patients with DM.     

Associations Between Abortion Services and Acceptance of Postabortion Contraception in Six Indian States

Women receiving induced abortions or postabortion care are at high risk of subsequent unintended pregnancy, and intervals of less than six months between abortion and subsequent pregnancy may be associated with adverse outcomes. This study highlights the prevalence and attributes of postabortion contraceptive acceptance from 2,456 health facilities in six major Indian states, among 292,508 women who received abortion care services from July 2011 through June 2014. Eighty‐one percent of the women accepted postabortion contraceptive methods: 53 percent short‐term, 11 percent intrauterine devices, and 16 percent sterilization. Postabortion contraceptive acceptance was highest among women who were aged 25 years and older, received first‐trimester services, received induced abortion, attended primary‐level health facilities, and had medical abortions. Doctors receiving post‐training support were more likely to offer contraceptives, but no association was observed between such support and acceptance of IUDs or sterilization. Comprehensive service‐delivery interventions, including ensuring availability of skilled providers and contraceptive commodities, offering clinical mentoring for providers, identifying and addressing provider bias, and improving provider counseling skills, can increase postabortion contraceptive acceptance and reduce unintended pregnancy.     

SARS-CoV-2 and Influenza Virus Co-Infection Cases Identified through ILI/SARI Sentinel Surveillance: A Pan-India Report

SARS-CoV-2/influenza virus co-infection studies have focused on hospitalized patients who usually had grave sequelae. Here, we report SARS-CoV-2/influenza virus co-infection cases from both community and hospital settings reported through integrated ILI/SARI (Influenza Like Illness/Severe Acute Respiratory Infection) sentinel surveillance established by the Indian Council of Medical Research. We describe the disease progression and outcomes in these cases. Out of 13,467 samples tested from 4 July 2021–31 January 2022, only 5 (0.04%) were of SARS-CoV-2/influenza virus co-infection from 3 different sites in distinct geographic regions. Of these, three patients with extremes of age required hospital admission, but none required ICU admission or mechanical ventilation. No mortality was reported. The other two co-infection cases from community settings were managed at home. This is the first report on SARS-CoV-2/Influenza virus co-infection from community as well as hospital settings in India and shows that influenza viruses are circulating in the community even during COVID-19. The results emphasize the need for continuous surveillance for multiple respiratory pathogens for effective public health management of ILI/SARI cases in line with the WHO (World Health Organization) recommendations.     

The human cytomegalovirus TRL11/IRL11-encoded FcγR binds differentially to allelic variants of immunoglobulin G1

Human cytomegalovirus (HCMV) has evolved several immune-evasion strategies. One strategy involves encoding Fcgamma receptor (Fc??R)-like proteins that thwart the Fc??-mediated effector functions. Our aim was to determine whether GM allotypes??immunoglobulin ?? chain determinants expressed primarily on the Fc segment??modulate this viral strategy through differential binding to the viral Fc??R. Results of our ELISA binding studies show that the mean absorbance values for binding to the HCMV TRL11/IRL11-encoded Fc??R were higher for IgG1 expressing the GM 3 allotype than for those expressing the allelic GM 1,2,17 determinants (p?=?0.0005), a finding with potential implications for genetic etiology of HCMV-associated diseases.     

Measuring community mental health in developing societies: evaluation of a checklist format in Nepal

BACKGROUND: There is growing recognition of the importance of mental health problems in developing countries. In large part, however, we have very limited epidemiological data at national and/or community levels about the prevalence of mental illnesses. AIMS: The purpose of this paper is to describe the reliability and validity characteristics of an assessment tool that may be useful for conducting community-level surveys (particularly in rural communities of developing countries) to obtain prevalence rates of mental illnesses. METHODS: We used a sample of adults residing in a rural village in Nepal to assess disorders with a modified version of the DSM-III-R Checklist. We evaluated construct validity, scale reliability, convergent validity and discriminant validity. RESULTS: There is strong evidence for the construct validity of generalized anxiety and depression in our sample. By contrast, the symptoms associated with mania and schizophrenia were not empirically distinct. Convergent validity is acceptable. As a test of validity characteristics, the pattern of sociodemographic correlations suggests that the specific social origins of disorder in Nepal will require further investigation. CONCLUSION: The first step in obtaining high quality information on the distribution of mental illness in developing countries is to establish some reliable and valid indicators of disorder. The checklist format for assessing disorder appears to meet this objective and offers the possibility that community-level prevalence studies can be reasonably conducted.     

Postirradiation neoplasia: A symposium

It is impossible to prove that radiation given for benign conditions in infancy and childhood is an etiologic factor in the subsequent development of carcinoma in the head and neck area. Nevertheless, the suggestive evidence is quite impressive and the information from many sources correlates well. There are some conflicting reports but, in general, it can be said that very high doses of radiation are less likely to be carcinogenic than lesser amounts. Very small doses of radiation are probably not carcinogenic either. In general, the younger the patient at the time of exposure to radiation, the greater is the risk of subsequent development of carcinoma. The breast seems to be an exception, however, as it is more sensitive to radiation carcinogenesis between the ages of 10 and 35. Chronic low doses of radiation seem to be more carcinogenic in humans. The latent interval between irradiation and the appearance of carcinoma in most sites averages about 30 years; leukemia tends to occur 5–8 years after irradiation. The atomic bomb data are confusing. Up to 30% of the Hiroshima bomb radiation consisted of neutrons, whereas the neutron radiation of the Nagasaki bomb was very low. The higher incidence of breast cancer associated with the former type of irradiation may be related to the higher carcinogenicity of neutrons. On the other hand, the lower normal incidence of breast carcinoma in Japanese women may be a modifying factor of RBE of radiation in tumor induction.Irradiation for malignant tumors in all parts of the body, although an exceedingly valuable addition to the cancer therapy armamentarium, probably predisposes to the later development of irradiation carcinoma in the long-term survivors. This becomes increasingly important as more children and young adults with malignant tumors are clinically cured of their original malignant tumor with multimodal therapy including irradiation.The risk of carcinogenesis in radiation-treated patients never disappears. These patients should be followed carefully for life.     

Further Evidence to Suggest That Microbodies Do Not Exist as Individual Entities

Male wild-type mice (Cs^a strain) were treated with ethyl-α-p-chlorophenoxyisobutyrate (CPIB), a hypolipidemic drug which enhances hepatic catalase synthesis and induces rapid and significant increase in the number of microbody (peroxisome) profiles in liver cells. Numerous microbody profiles, several of them appearing in clusters and retaining membranous continuities, were observed in liver cells of CPIB-treated mice. They showed a significant variation in size and configuration, and the presence or absence of the nucleoid or core did not appear to bear any relation to the size or shape of microbody profiles. Nucleoids were encountered frequently in microbody profiles measuring as small as 0.1 μ in diameter. Numerous continuities between two or more anucleoid and/or nucleoid-containing microbody profiles of different sizes and shapes were seen. These findings are inconsistent with the concept that the smaller peroxisomes are the possible precursors or progenitors of their larger counterparts. Detailed examination of numerous electron micrographs revealed irregular dilatations and tortuosities of the endoplasmic reticulum (ER) containing electron-opaque peroxisomal material displaying the characteristic appearance of matrix and usually containing irregular cores. Transitions of rough ER to smooth ER in which microbody proteins accumulated were also apparent. Numerous continuities between several microbody profiles and continuities between microbody profiles and ER are interpreted as accumulations of peroxisomal proteins in dilated tortuous channels of ER. These observations strongly suggest that the microbody proteins constitute a common pool, circulating constantly in the dilated ER channels. The size, shape and number of microbody profiles appear to reflect the amount of peroxisomal proteins present in the pool. These observations clearly suggest that the microbodies do not exist as individual entities.