A Rare Case of Undescended Caecum Accompanied by Looped Retroperitoneal Appendix.

Intestinal malrotations are associated with various anatomical anomalies. We report a unique case wherein the caecum was located in the right lumbar region instead of the right iliac fossa. The ileo-caecal junction was also placed higher up. The appendix was ‘uncinate’ shaped, highly coiled and retroperitoneal with the absence of meso-appendix. Both, the caecum and appendix were supplied by ascending branch of the ileocolic artery instead of the descending branch. Further, we also observed that the ascending colon was very short and sub-hepatic in position. Such type of variations is of clinical and surgical importance in diagnosis and treatment of appendicitis

CLINICAL OUTCOMES OF USE OF HYDROXYCHLOROQUINE IN PARADOXICAL TUBERCULOSIS-IMMUNE RECONSTITUTION INFLAMMATORY SYNDROME IN HIV-INFECTED PATIENTS.

 Objective: Immune reconstitution inflammatory syndrome (IRIS) is an inflammatory reaction in HIV-infected patients after initiation of antiretroviral therapy (ART) resulting from restored immunity to specific infectious or non-infectious antigens. The most common condition where IRIS has been reported is tuberculosis (TB). Various mechanisms have been proposed and studied to account for the immune regulatory role of hydroxychloroquine (HCQ). This study is done to identify clinical outcome in HIV-TB patients with IRIS after given with HCQ.Methods: An uncontrolled longitudinal study was conducted among HIV-infected patients with TB initiated on ART and developed IRIS between July 2013 and June 2015 in a South Indian HIV care hospital.Results: A total of 40 patients have developed IRIS with mean age of 35.87 years and 77.5 % of them were males. At the time of IRIS occurrence, the mean body mass index was found to be 19.17 kg/m2 and CD4 count was 200 cells/mm3. The time duration took to get improvement in majority of the patients was 4–12 weeks.Conclusion: There was definite improvement seen in patients who received HCQ in TB-IRIS condition

Trifurcated hepatic artery proper with unusual course and termination of right hepatic artery into fossa for gall bladder.

Variant vascular pattern affecting the hepatic artery is well documented. We here report a case of trifurcated hepatic artery proper associated with abnormal course, branching and termination of right hepatic artery. In the present case, hepatic artery proper trifurcated into right, middle and left branches about 2 cm before reaching porta hepatis. Left and middle braches entered the liver through the porta hepatis as normal but, the right hepatic artery took an unusual course towards the fossa for gall bladder and passed between portal vein behind and common hepatic duct, anteriorly. Just before its termination, it gave an additional hepatic branch to the liver and a cystic branch to the gall bladder. The rare course, branching pattern and abnormal termination of the right hepatic artery as reported here, are vulnerable to damage during intraoperative procedures if not carefully observed. Hence, prior knowledge of its variant anatomy is imperative during segmental resection of the liver and any intraoperative procedures performed in this region

Hemodialysis in infants and small children

Hemodialysis in infants and small children requires specialized nursing staff, equipment and adequate access. The techniques, requirements and available equipment for this population are discussed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47834/1/467_2004_Article_BF00868283.pd

Glucose and glutamine fuel protein O-GlcNAcylation to control T cell self-renewal and malignancy

Sustained glucose and glutamine transport are essential for activated T lymphocytes to support ATP and macromolecule biosynthesis. We now show that glutamine and glucose also fuel an indispensible dynamic regulation of intracellular protein O-GlcNAcylation at key stages of T cell development, transformation and differentiation. Glucose and glutamine are precursors of UDP-GlcNAc, a substrate for cellular glycosyltransferases. Immune activated T cells contained higher concentrations of UDP-GlcNAc and increased intracellular protein O-GlcNAcylation controlled by the enzyme O-GlcNAc glycosyltransferase as compared to naïve cells. We identified Notch, the T cell antigen receptor and c-Myc as key controllers of T cell protein O-GlcNAcylation, via regulation of glucose and glutamine transport. Loss of O-GlcNAc transferase blocked T cell progenitor renewal, malignant transformation, and peripheral T cell clonal expansion. Nutrient-dependent signaling pathways regulated by O-GlcNAc glycosyltransferase are thus fundamental for T cell biology

Cerebral Changes Occurring in Arginase and Dimethylarginine Dimethylaminohydrolase (DDAH) in a Rat Model of Sleeping Sickness

Involvement of nitric oxide (NO) in the pathophysiology of human African trypanosomiasis (HAT) was analyzed in a HAT animal model (rat infected with Trypanosoma brucei brucei). With this model, it was previously reported that trypanosomes were capable of limiting trypanocidal properties carried by NO by decreasing its blood concentration. It was also observed that brain NO concentration, contrary to blood, increases throughout the infection process. The present approach analyses the brain impairments occurring in the regulations exerted by arginase and N(G), N(G)-dimethylarginine dimethylaminohydrolase (DDAH) on NO Synthases (NOS). In this respect: (i) cerebral enzymatic activities, mRNA and protein expression of arginase and DDAH were determined; (ii) immunohistochemical distribution and morphometric parameters of cells expressing DDAH-1 and DDAH-2 isoforms were examined within the diencephalon; (iii) amino acid profiles relating to NOS/arginase/DDAH pathways were established.Arginase and DDAH activities together with mRNA (RT-PCR) and protein (western-blot) expressions were determined in diencephalic brain structures of healthy or infected rats at various days post-infection (D5, D10, D16, D22). While arginase activity remained constant, that of DDAH increased at D10 (+65%) and D16 (+51%) in agreement with western-blot and amino acids data (liquid chromatography tandem-mass spectrometry). Only DDAH-2 isoform appeared to be up-regulated at the transcriptional level throughout the infection process. Immunohistochemical staining further revealed that DDAH-1 and DDAH-2 are contained within interneurons and neurons, respectively.In the brain of infected animals, the lack of change observed in arginase activity indicates that polyamine production is not enhanced. Increases in DDAH-2 isoform may contribute to the overproduction of NO. These changes are at variance with those reported in the periphery. As a whole, the above processes may ensure additive protection against trypanosome entry into the brain, i.e., maintenance of NO trypanocidal pressure and limitation of polyamine production, necessary for trypanosome growth

Global, regional, and national prevalence and mortality burden of sickle cell disease, 2000-2021: a systematic analysis from the Global Burden of Disease Study 2021

BACKGROUND: Previous global analyses, with known underdiagnosis and single cause per death attribution systems, provide only a small insight into the suspected high population health effect of sickle cell disease. Completed as part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021, this study delivers a comprehensive global assessment of prevalence of sickle cell disease and mortality burden by age and sex for 204 countries and territories from 2000 to 2021. METHODS: We estimated cause-specific sickle cell disease mortality using standardised GBD approaches, in which each death is assigned to a single underlying cause, to estimate mortality rates from the International Classification of Diseases (ICD)-coded vital registration, surveillance, and verbal autopsy data. In parallel, our goal was to estimate a more accurate account of sickle cell disease health burden using four types of epidemiological data on sickle cell disease: birth incidence, age-specific prevalence, with-condition mortality (total deaths), and excess mortality (excess deaths). Systematic reviews, supplemented with ICD-coded hospital discharge and insurance claims data, informed this modelling approach. We employed DisMod-MR 2.1 to triangulate between these measures-borrowing strength from predictive covariates and across age, time, and geography-and generated internally consistent estimates of incidence, prevalence, and mortality for three distinct genotypes of sickle cell disease: homozygous sickle cell disease and severe sickle cell β-thalassaemia, sickle-haemoglobin C disease, and mild sickle cell β-thalassaemia. Summing the three models yielded final estimates of incidence at birth, prevalence by age and sex, and total sickle cell disease mortality, the latter of which was compared directly against cause-specific mortality estimates to evaluate differences in mortality burden assessment and implications for the Sustainable Development Goals (SDGs). FINDINGS: Between 2000 and 2021, national incidence rates of sickle cell disease were relatively stable, but total births of babies with sickle cell disease increased globally by 13·7% (95% uncertainty interval 11·1-16·5), to 515 000 (425 000-614 000), primarily due to population growth in the Caribbean and western and central sub-Saharan Africa. The number of people living with sickle cell disease globally increased by 41·4% (38·3-44·9), from 5·46 million (4·62-6·45) in 2000 to 7·74 million (6·51-9·2) in 2021. We estimated 34 400 (25 000-45 200) cause-specific all-age deaths globally in 2021, but total sickle cell disease mortality burden was nearly 11-times higher at 376 000 (303 000-467 000). In children younger than 5 years, there were 81 100 (58 800-108 000) deaths, ranking total sickle cell disease mortality as 12th (compared to 40th for cause-specific sickle cell disease mortality) across all causes estimated by the GBD in 2021. INTERPRETATION: Our findings show a strikingly high contribution of sickle cell disease to all-cause mortality that is not apparent when each death is assigned to only a single cause. Sickle cell disease mortality burden is highest in children, especially in countries with the greatest under-5 mortality rates. Without comprehensive strategies to address morbidity and mortality associated with sickle cell disease, attainment of SDG 3.1, 3.2, and 3.4 is uncertain. Widespread data gaps and correspondingly high uncertainty in the estimates highlight the urgent need for routine and sustained surveillance efforts, further research to assess the contribution of conditions associated with sickle cell disease, and widespread deployment of evidence-based prevention and treatment for those with sickle cell disease. FUNDING: Bill & Melinda Gates Foundation