Endoscopic ultrasound‐guided fine‐needle aspiration diagnosis of large cell neuroendocrine carcinoma of the gallbladder and common bile duct: Report of a case

Endoscopic ultrasound‐guided fine‐needle aspiration (EUS‐FNA) allows a reliable and accurate diagnosis of neoplasms of the gallbladder and bile ducts. We report the cytopathologic findings of a case of large cell neuroendocrine carcinoma (LCNEC) of the gallbladder and extrahepatic bile ducts in a 67‐year‐old woman who presented with progressive abdominal pain and jaundice. EUS‐FNA of the mass involving the common bile duct and of a porta hepatis lymph node showed abundant cellularity with tumor cells arranged singly and occasionally in tight and loose clusters and rosette‐like structures in a background showing extensive necrotic debris. The tumor cells were predominantly plasmacytoid, showed a moderate amount of focally vacuolated cytoplasm and large round to oval hyperchromatic nuclei with prominent nucleoli, numerous mitoses, and apoptotic bodies. The differential diagnosis included poorly differentiated adenocarcinoma, lymphoma, melanoma, and poorly differentiated neuroendocrine carcinoma (NEC), large cell type. The tumor cells were strongly and diffusely positive for cytokeratin AE1/AE3, CD56, synaptophysin, and chromogranin and showed a very high proliferative fraction on Ki67 staining, supporting the diagnosis of a high‐grade NEC. Due to the large size of the neoplastic cells, moderate amounts of cytoplasm and prominent nucleoli, a diagnosis of LCNEC was made on the EUS‐FNA sample. Despite the prompt institution of chemotherapy, the patient died shortly thereafter and the diagnosis was confirmed at autopsy. This is to our knowledge the first case of LCNEC of the gallbladder and bile ducts diagnosed by EUS‐FNA. Diagn. Cytopathol. 2013;41:1091–1095. © 2012 Wiley Periodicals, Inc.     

Neuromuscular transmission in hypoxemic patients with chronic obstructive pulmonary disease

Many studies have focused on the systemic effects of chronic obstructive pulmonary disease (COPD), but none has examined neuromuscular junction transmission (NMT). We evaluated NMT dysfunction using single-fiber electromyography (SFEMG) in patients with COPD. Twenty patients with COPD and 20 age-matched healthy controls were included in the study. All patients and controls underwent SFEMG. Abnormal NMT was found in seven of 20 patients (35%), but in none of the control subjects. The COPD patients were subgrouped according to the presence of hypoxemia. The patients with normoxemia were classified as Group 1, and the patients with hypoxemia were classified as Group 2. Abnormal NMT was found in six patients in Group 2 and in one in Group 1. While there was significant difference in terms of abnormal NMT between Group 2 and the controls, there was none between Group 1 and the controls. Our results show that NMT abnormalities can be present in hypoxemic patients with COPD.     

The avian and mammalian host range of highly pathogenic avian H5N1 influenza

Highly pathogenic H5N1 influenza viruses have been isolated from a number of avian and mammalian species. Despite intensive control measures the number of human and animal cases continues to increase. A more complete understanding of susceptible species and of contributing environmental and molecular factors is crucial if we are to slow the rate of new cases. H5N1 is currently endemic in domestic poultry in only a handful of countries with sporadic and unpredictable spread to other countries. Close contact of terrestrial bird or mammalian species with infected poultry/waterfowl or their biological products is the major route for interspecies transmission. Intra-species transmission of H5N1 in mammals, including humans, has taken place on a limited scale though it remains to be seen if this will change; recent laboratory studies suggest that it is indeed possible. Here we review the avian and mammalian species that are naturally susceptible to H5N1 infection and the molecular factors associated with its expanded host range.     

Hierarchical biomineralization of calcium carbonate regulated by silk microspheres

As an analog of the main protein contained in nacre regenerated Bombyx mori silk fibroin has a significant influence on the morphology and polymorphic nature of CaCO₃ in the biomineralization process. A number of studies have implied that the self-assembling aggregate structure of silk fibroin is a key factor in controlling CaCO₃ aggregation. Further insight into this role is necessary with a particular need to prepare silk fibroin aggregates with homogeneous structures to serve as templates for the mineralization process. Here we have prepared homogeneous silk microspheres to serve as templates for CaCO₃ mineralization in order to provide an experimental insight into silk-regulated crystallization processes. CaCO₃ particles with different nano- and microstructures, and their polymorphs, were successfully formed by controlling the mineralization process. The key function of silk aggregation in controlling the morphology and polymorphic nature of CaCO₃ particles was confirmed. A regulating effect of silk on the spatial features was also observed. A two-step process for silk fibroin-regulated biomineralization was found, with different levels of heterogeneous nucleation and aggregation. A full understanding of silk fibroin-regulated biomineralization mechanisms would help in understanding the function of organic polymers in natural biomineralization, and provide a way forward in the design and synthesis of new materials in which organic–inorganic interfaces are the keys to function, biological interfaces and many related material features.     

Schistosome Egg Antigens Elicit a Proinflammatory Response by Trophoblast Cells of the Human Placenta

Schistosomiasis affects nearly 40 million women of reproductive age. Many of these women are infected while pregnant and lactating. Several studies have demonstrated transplacental trafficking of schistosome antigens; however, little is known regarding how these antigens affect the developing fetus and placenta. To evaluate the impact of schistosomiasis on trophoblasts of the human placenta, we isolated primary trophoblast cells from healthy placentas delivered at term. These trophoblasts were placed in culture and treated with Schistosoma japonicum soluble egg antigens (SEA) or plasma from S. japonicum-infected pregnant women. Outcomes measured included cytokine production and activation of signal transduction pathways. Treatment of primary human trophoblast cells with SEA resulted in upregulation of the proinflammatory cytokines interleukin 6 (IL-6) and IL-8 and the chemokine macrophage inflammatory protein 1α (MIP-1α). Cytokine production in response to SEA was dose dependent and reminiscent of production in response to other proinflammatory stimuli, such as Toll-like receptor 2 (TLR2) and TLR4 agonists. In addition, the signaling pathways extracellular signal-regulated kinase 1/2 (ERK1/2), Jun N-terminal protein kinase (JNK), p38, and NF-κB were all activated by SEA in primary trophoblasts. These effects appeared to be mediated through both carbohydrate and protein epitopes of SEA. Finally, primary trophoblasts cocultured with plasma from S. japonicum-infected pregnant women produced increased levels of IL-8 compared to trophoblasts cocultured with plasma from uninfected pregnant women. We report here a direct impact of SEA on primary human trophoblast cells, which are critical for many aspects of a healthy pregnancy. Our data indicate that schistosome antigens can activate proinflammatory responses in trophoblasts, which might compromise maternal-fetal health in pregnancies complicated by schistosomiasis.     

Mutational diversity and hot spots in the alpha-sarcoglycan gene in autosomal recessive muscular dystrophy (LGMD2D).

Sarcoglycanopathies are a genetically heterogeneous group of autosomal recessive muscular dystrophies in which the primary defect may reside in any of the genes coding for the different partners of the sarcolemmal sarcoglycan (SG) complex: the alpha-SG (LGMD2D at 17q21.2), the beta-SG (LGMD2E at 4q12), the gamma-SG (LGMD2C at 13q12), and the delta-SG (LGMD2F at 5q33). We report a series of 20 new unrelated families with 14 different mutations in the alpha-SG gene. Along with the mutations that we previously reported this brings our cohort of patients with alpha-sarcoglycanopathy to a total of 31 unrelated patients, carrying 25 different mutations. The missense mutations reside in the extracellular domain of the protein. Five of 15 missense mutations, carried by unrelated subjects on different haplotype backgrounds and of widespread geographical origins, account for 58% of the mutated chromosomes, with a striking prevalence of the R77C substitution (32%). The severity of the disease varies strikingly and correlates at least in part with the amount of residual protein and the type of mutation. The recurrent R284C substitution is associated with a benign disease course.     

Pregnancy during the COVID-19 pandemic: a qualitative examination of ways of coping

Archives of Women's Mental Health - The COVID-19 pandemic and related public health restrictions have impacted the mental health and coping strategies of many population groups, including...     

Associations between maternal depression and mother and infant oxytocin receptor gene (OXTR_rs53576) polymorphisms

Polymorphisms in the oxytocin receptor gene, OXTR_rs53576, have been linked to differences in maternal sensitivity and depressive symptoms. Although some studies suggest the A allele confers risk for mood disorders, individuals homozygous for the G allele may exhibit greater sensitivity to both positive and negative social experiences, including in the mother–infant dyad. Given the bi-directional nature of mother–infant influences on maternal mood, we tested the association between both mothers’ and infants’ OXTR_rs53576 genotype and maternal depression, as assessed through a self-report inventory. Although Beck Depression Inventory (BDI-II) scores were significantly higher for GG in comparison to AG/AA mothers, and for mothers of GG in comparison to AG/AA infants, an ANCOVA revealed that after sociodemographic risk factors had been controlled, infants’, but not mothers’, OXTR genotype predicted maternal depression scores, with no significant interaction between the two. The effect of infant OXTR on maternal depression was not explained by maternal reports of difficult infant temperament. We propose that GG infants have an enhanced capacity for processing both positive and negative socially meaningful contextual information, first amplifying and then differentially perpetuating negative affectivity in mothers who exhibit depressive characteristics.