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Objective To evaluate the long‐term safety of rituximab in an observational cohort of patients with rheumatoid arthritis (RA) who had an inadequate response to ≥1 anti–tumor necrosis factor therapy in the US (SUNSTONE [Study of the Safety of Rituxan in Patients With Rheumatoid Arthritis After an Inadequate Response to Previous Anti‐TNF Therapy] registry). Methods In this prospective, observational cohort study, patients received rituximab according to their physician's standard practice and were evaluated at standard‐of‐care follow‐up visits at least every 6 months. The primary outcome was the incidence of protocol‐defined significant infections. Secondary outcomes included serious adverse events potentially associated with rituximab, cardiovascular or thrombotic events, seizures, deaths, and pregnancies. Post hoc analyses assessed outcomes by concomitant medication use. Results Overall, 989 patients (safety‐evaluable population) received ≥1 dose of rituximab, with a total follow‐up of 3,844 patient‐years (mean duration 3.9 years). In total, 341 significant infections occurred in 197 patients (19.9%). The incidence rates (95% confidence intervals [95% CIs]) for significant infections, cardiovascular or thrombotic events, and seizures were 8.87 (95% CI 7.98–9.86), 1.95 (95% CI 1.56–2.45), and 0.18 (95% CI 0.09–0.38) per 100 patient‐years, respectively. The incidence of significant infections did not increase with time or with cumulative rituximab exposure. During the study, 64 patients died (crude mortality rate 1.66 per 100 patient‐years [95% CI 1.30–2.13]). The most common causes of death were infections (n = 19), malignancy (n = 14), and cardiovascular events (n = 13). Eight pregnancies were reported in 7 patients. Conclusion In patients with RA treated with rituximab for up to 5 years, the rates of significant infections were stable over time and higher in patients who received long‐term systemic steroid treatment.

Aim: Metabolic bone disorders and reduced bone mass are common complications in patients with biliary cirrhosis. As a result of there being no clear etiology, no specific therapy has been established yet. Previous studies have reported that quercetin, a plant-derived flavonoid, might improve bone quality. The present study was designed to investigate the effect of quercetin on bone strength of biliary cirrhotic rats. Methods: Twenty-four male Sprague–Dawley rats aged 6–7 months were randomized into three groups of eight. One group served as control (sham operated), while the other two groups underwent a complete bile duct ligation (BDL). Four weeks after the operation, serum bilirubin, alkaline phosphatase, alanine aminotransferase and aspartate aminotransferase were measured in animal blood samples to confirm the occurrence of cirrhosis in the BDL rats. Then, one of the BDL groups received placebo and the other one was injected once a day with 150 µmol/kg of quercetin for 4 weeks. At the end of the study, femora were removed and tested for bone strength and histomorphometric parameters. The serum levels of osteocalcin, C-terminal cross-linked telopeptide of type I collagen, calcium and phosphorus were determined as bone turnover markers. Results: Femur breaking strength was dramatically lower in the BDL group compared with control. However, receiving quercetin could reverse the deteriorating effect of cirrhosis on bone strength of BDL rats. Quercetin could noticeably elevate osteocalcin as a bone formation marker. Conclusion: These data suggest that quercetin can significantly improve bone strength particularly due to increasing bone formation in biliary cirrhosis.

Summary Histology of the tongue, including apex, root and body, in four adult Caspian miniature horses was examined. Serial sections with 6 μm thickness were stained with haematoxylin–eosin and Masson trichrome and studied under light microscope. The tongue was covered by stratified squamous epithelium. It was thick and keratinized bearing numerous lingual papillae on the dorsum, mostly filiform with a very fine keratinized thread projecting above the surface and bending backward. The fungiform papillae were sparsely scattered among the filiform papillae and covered with keratinized squamous epithelium. Few taste buds were detected on it. The two very large vallate papillae were detected on the dorsum, just rostral to the root, which were covered with stratified squamous epithelium with relatively high amounts of taste buds in the epithelium of the surrounding grooves. The foliate papillae were present near the palatoglossal arch and had a few taste buds. The epithelium covering the ventral surface of the tongue was thin and keratinized. The lingual muscle core consisted of transverse, longitudinal and perpendicular bundles of skeletal muscle fibres. Clusters of minor salivary glands were present between the muscle fibres and lamia propria. Most of the lingual glands were mucous and most of the gustatory ones were serous type. The mid-dorsal special structure of the tongue (dorsal lingual cartilage) contained sparse skeletal muscle fibres and was rich in white adipose tissue. Hyaline cartilage, routinely observed in this structure in the horses, was not detected in Caspian miniature horse.

Forty-six rats fed a Zn-deficient diet for 18 days, were divided into three groups and treated with Zn-deficient diet (GI), a normal (Zn-adequate) diet (GII) or a pharmacological Zn therapy diet (GIII) for 3 days. For light and electron microscopy, samples were taken at times 0, 8, 12, 24 and 72 h after treatment. In treatment GI, at all times, all rats had esophageal parakeratosis. With treatment GII, there was a variable progression toward normalization of the epithelium at 12 and 24 h. At 72 h there was almost complete recovery of normal epithelium. In treatment GIII at 8 h, large, light cells in the basal layer were shown to be present between dark cylindrical cells, a finding which was transitionary and disappeared at 12 h. Also, a thin keratinized layer was observed above the granular layer at 12 h. Recovery had progressed at 24 h and was complete after 72 h. The results are discussed in terms of a potential role of Zn in the sequence of cytochemical events in epithelial differentiation.

The cecum is a great cul-de sac intercalated between the small intestine and the colon. It has a remarkable size in the equine and digestion of more than 30% of total cellulose and production of volatile fatty acids by anaerobic metabolism of cellulose by its micro flora were made on it. It has also a substantial number of lymphatic nodules, which in horses are located near the apex. Topographically, cecum is situated chiefly to the right of the median plane and occupies around the whole volume of there in the abdominal cavity. The histological structure of the lymphatic follicles and their distributions pattern throughout the cecum in five healthy mature miniature horses (an special species of horses lives only in north of Iran) were studied (Fig. 1a). Each cecum was divided into three parts, namely, the base, body and apex, and samples were taken from each part immediately after slaughter and fixed with 10% buffered formalin. Routine histological laboratory techniques were made and 6 μm ?sections were cut and stained with haematoxylin and eosin staining and studied under light microscope. Lymphatic nodules were mostly found in the submucosa, but they disrupted the muscularis mucosa and merged into the lamina propria (Fig. 1c). The thickness of the mucosa and submucosa at these sites was smaller, and the epithelium that covered the mucosa was here modified into simple squamous or low cuboidal epithelia with dark and flattened nuclei (Figs 1b,d). The large and small lymphatic nodules were extensively accumulated in the apex, forming a nearly continuous layer in lamina propria and submucosa. However, they were less prominent at the base and least in the body of the cecum. (1 A) [ Abdominal viscera of miniature horse: right view. The right lateral wall is removed, right ventral part of colon (thick arrow), cecum (thin arrow). B: Photomicrograph from the apex of cecum in miniature horse, large numbers of lymphatic nodules were seen in lamina propria and sub mucosa (arrows) , H&E, 32x. C: Photomicrograph from the base of cecum in miniature horse, lymphatic nodule (thin arrow), discontinues muscularis mocusa (thick arrow), H&E, 100x. D: Photomicrograph from the epithelium covering the base of cecum in miniature horse, normalepithelia (thick arrow) ]