Recurrent intestinal obstruction with acquired angio-oedema, due to C1-esterase inhibitor deficiency.

A 52-year male with past history of ulcerative colitis 20 years back (now in remission), developed recurrent small intestinal obstruction at intervals of a few months. CT scan did not detect the cause initially. A repeat CT scan (USA) showed interbowel fluid with transient ascites (serum albumin normal). Angio-oedema was suspected and low C4 with C1-esterase inhibitor (C1-INH) deficiency confirmed the diagnosis. Further investigation showed he was suffering from a chronic low grade small B cell lymphoma. He was treated with Rituximab 375 mg/m2 at intervals of one week for 4 weeks. He is asymptomatic with Transexamic acid (500 mg TDS) for last 1½ years.

Unveiling the Genetic Symphony: Harnessing CRISPR-Cas Genome Editing for Effective Insect Pest Management.

Phytophagous insects pose a significant threat to global crop yield and food security. The need for increased agricultural output while reducing dependence on harmful synthetic insecticides necessitates the implementation of innovative methods. The utilization of CRISPR-Cas (Clustered regularly interspaced short palindromic repeats) technology to develop insect pest-resistant plants is believed to be a highly effective approach in reducing production expenses and enhancing the profitability of farms. Insect genome research provides vital insights into gene functions, allowing for a better knowledge of insect biology, adaptability, and the development of targeted pest management and disease prevention measures. The CRISPR-Cas gene editing technique has the capability to modify the DNA of insects, either to trigger a gene drive or to overcome their resistance to specific insecticides. The advancements in CRISPR technology and its various applications have shown potential in developing insect-resistant varieties of plants and other strategies for effective pest management through a sustainable approach. This could have significant consequences for ensuring food security. This approach involves using genome editing to create modified insects or crop plants. The article critically analyzed and discussed the potential and challenges associated with exploring and utilizing CRISPR-Cas technology for reducing insect pest pressure in crop plants.

Insect-pathogen crosstalk and the cellular-molecular mechanisms of insect immunity: uncovering the underlying signaling pathways and immune regulatory function of non-coding RNAs.

Multicellular organisms are constantly subjected to pathogens that might be harmful. Although insects lack an adaptive immune system, they possess highly effective anti-infective mechanisms. Bacterial phagocytosis and parasite encapsulation are some forms of cellular responses. Insects often defend themselves against infections through a humoral response. This phenomenon includes the secretion of antimicrobial peptides into the hemolymph. Specific receptors for detecting infection are required for the recognition of foreign pathogens such as the proteins that recognize glucans and peptidoglycans, together referred to as PGRPs and ßGRPs. Activation of these receptors leads to the stimulation of signaling pathways which further activates the genes encoding for antimicrobial peptides. Some instances of such pathways are the JAK-STAT, Imd, and Toll. The host immune response that frequently accompanies infections has, however, been circumvented by diseases, which may have assisted insects evolve their own complicated immune systems. The role of ncRNAs in insect immunology has been discussed in several notable studies and reviews. This paper examines the most recent research on the immune regulatory function of ncRNAs during insect-pathogen crosstalk, including insect- and pathogen-encoded miRNAs and lncRNAs, and provides an overview of the important insect signaling pathways and effector mechanisms activated by diverse pathogen invaders.

Impact of mass drug administration on elimination of lymphatic filariasis in Surat city, India.

Lymphatic filariasis (LF) is one of the major public health problems in some of the endemic districts in India including Surat city of Gujarat province. Historical data reveals that in 1960s, Surat city had infection rate of about 23% and infectivity rate of 1.6%. Since then, Surat city has been reporting the cases of Lymphoedema and hydrocele. Filaria Control Unit was established under National Filaria Control Programme to detect and provide treatment to the cases. Based on the reports of NFCP, Surat City has been considered as LF endemic. During 2004, the country launched campaign of Elimination of Lymphatic Filariasis through Mass Drug Administration (MDA) with annual single dose of 6 mg/kg body weight of DEC tablets in all LF endemic districts including Surat city. Four rounds of MDA (2004-2007) had shown 41% reduction in mf rate, with drastic reduction in infection rate of 88% and 100% in infectivity rate. Serious adverse effect (SAE) after 4th round of MDA was insignificant (< 0.5%) during 2007. An assessment by surveying 5058 people in different parts of Surat city revealed the drug distribution coverage of more than 95% but actual drug compliance between 70-90%. Analysis of the data revealed that though the overall Microfilaria rate has been reduced due to MDA, higher Microfilaria rate was noticed in North zone of city where the migrant populations influx is higher. The observation and analysis of the data in Surat city towards elimination of Lymphatic filariasis has been discussed in this paper.

Organ donation: victory after death.

Despite the Transplantation of Human Organ Act passed in Indian Parliament in 1994, cadaver liver and/or kidney transplant are infrequently performed (in a few private hospitals) in our country compared to living donor liver or kidney transplant. The need for performing more cadaver liver and/or kidney transplants in private and public hospitals is obvious. Immediate measures which should be taken to facilitate more cadaver organ transplant both in private and public hospitals are suggested. Organ donation is for an individual or a family an invaluable opportunity, to register victory after death.

Does model for end-stage liver disease (MELD) require modification?

Model for End-stage Liver Disease (MELD) measures serum bilirubin (mg/dL), serum albumin (g/dL), International Normalised Ratio (INR) for prothrombin time. MELD score accurately predicts survival in 3 months for cirrhotic patients on the waiting list of liver transplantation. In about 15% of patients, it does not accurately predict survival and hence MELD-Na is recommended. MELD score is a poor predictor of survival after liver transplantation. Downgrading of MELD score for age of recipient and chance of recurrence of the disease is recommended to accurately predict survival after liver transplantation.

Is dermis fat arthroplasty better than plain gap arthroplasty? A prospective randomised controlled trial.

The aim of the study was to compare interpositional arthroplasty using a dermis fat graft with gap arthroplasty in the management of ankylosis of the temporomandibular joint (TMJ). We organised a prospective randomised study of 22 patients who presented with ankylosis of the TMJ. They were randomised to be treated with either plain gap arthroplasty or dermis fat arthroplasty, and the predictor variable was the method of treatment. The primary outcome variables were mouth opening and pain on jaw exercises. Pain and interincisal opening were measured on day 5, day 14, at the end of one month, and at six months, one year, two years, and three years. There was a significant difference between the two groups on two occasions: postoperative day 5 (p=0.013) and at one year (p=0.018). The mean (SD) scores for mouth-opening were higher in the dermis fat group at all times (41.20 (4.69) mm compared with 39.50 (2.46) mm in gap arthroplasty at two years, and 41.40 (3.60) mm compared with 38.9 (2.02) mm at three years). The visual analogue pain scores were also lower in the dermis fat graft group. The groups showed similar results at the end of three years follow up, with no significant difference in mouth opening. We conclude therefore that the two techniques have similar outcomes in the management of ankylosis of the TMJ.

Cryptogenic cirrhosis: a vanishing entity.

The diagnosis of cryptogenic cirrhosis (cirrhosis of unknown etiology) has dramatically decreased, following the discovery of hepatitis B virus (1965), hepatitis D virus (1977), hepatitis C virus (1989). Improving the diagnostic criteria for Autoimmune Hepatitis, by devising the scoring system and the recognition of the fact that Nonalcoholic Steatohepatitis can progress to cirrhosis (in 8 to 10 years), further reduced the diagnosis of cryptogenic cirrhosis. Establishing the etiology of cirrhosis in the vast majority of the patients has provided numerous options for its prevention and treatment.

Intra-muscular haemangioma of the masseter: A clinical update and differential diagnosis of a rare entity.

The intramuscular haemangioma (IMH) is a rare variant of unknown aetiology and comprises 0.8% of soft tissue haemangiomas. Less than 20% of IMHs occur in the craniofacial region of which the masseter is the most common site. It presents as a non-specific, painful soft tissue enlargement in young adults. Symptoms common to vascular lesions usually are absent. Due to the paucity of clinical symptoms, advanced imaging techniques like MRIs are needed to clinch a definitive pre-operative diagnosis. The therapeutic modalities mentioned in the literature range from total surgical excision to non-surgical methods like cryotherapy, sclerotherapy, embolization and feeder vessel ligation. We present a case of an intra-massetric IMH in a 16-year-old male which was treated by total surgical excision with a follow up of 3 years. We also stress on the differential diagnosis of intra-massetric lesions and the key findings of the various imaging modalities available for IMH.

Rapid generation of broad T-cell immunity in humans after a single injection of mature dendritic cells.

Dendritic cells (DCs) are potent antigen-presenting cells that initiate protective T-cell immunity in mice. To study the immunogenicity of DCs in humans, we injected 9 healthy subjects subcutaneously with a control injection of autologous monocyte-derived, mature DCs, followed 4-6 weeks later by DCs pulsed with keyhole limpet hemocyanin (KLH), HLA-A*0201-positive restricted influenza matrix peptide (MP), and tetanus toxoid (TT). Four more subjects received these antigens without DCs. Injection of unpulsed DCs, or antigens alone, failed to immunize. Priming of CD4(+) T cells to KLH was observed in all 9 subjects injected with KLH-pulsed DCs, and boosting of TT-specific T-cell immunity was seen in 5 of 6 subjects injected with TT-pulsed DCs. Injection of antigen-pulsed DCs led to a severalfold increase in freshly isolated MP-specific, IFN-gamma-secreting CD8(+) T cells in all 6 HLA-A*0201-positive subjects, as early as 7 days after injection. When T cells were boosted in culture, there was an increase in MHC tetramer-binding cells and cytotoxic T cells after DC vaccination. These data provide the first controlled evidence of the immunogenicity of DCs in humans, and demonstrate that a single injection of mature DCs rapidly expands T-cell immunity.

Rabbit sucrase-isomaltase contains a functional intestinal receptor for Clostridium difficile toxin A.

The intestinal effects of Clostridium difficile toxin A are inidated by toxin binding to luminal enterocyte receptors. We reported previously that the rabbit ileal brush border (BB) receptor is a glycoprotein with an alpha-d-galactose containing trisaccharide in the toxin-binding domain (1991. J. Clin. Invest. 88:119-125). In this study we characterized the rabbit ileal BB receptor for this toxin. Purified toxin receptor peptides of 19 and 24 amino acids showed 100% homology with rabbit sucrase-isomaltase (SI). Guinea pig receptor antiserum reacted in Western blots with rabbit SI and with the purified toxin receptor. Antireceptor IgG blocked in vitro binding of toxin A to rabbit ileal villus cell BB. Furthermore, anti-SI IgG inhibited toxin A-induced secretion (by 78.1%, P < 0.01), intestinal permeability (by 80.8%, P < 0.01), and histologic injury (P < 0.01) in rabbit ileal loops in vivo. Chinese hamster ovary cells transfected with SI cDNA showed increased intracellular calcium increase in response to native toxin (holotoxin) or to a recombinant 873-amino acid peptide representing the receptor binding domain of toxin A. These data suggest that toxin A binds specifically to carbohydrate domains on rabbit ileal SI, and that such binding is relevant to signal transduction mechanisms that mediate in vitro and in vivo toxicity.

Investigations proposed to accurately classify chronic gastritis.

Patients of chronic gastritis should be investigated with gastric mucosal biopsy, parietal cell antibody, intrinsic factor antibody, Helicobacter pylori antibody, urea breath test or faecal antigen test for Helicobacter pylori, to accurately classify them. The results of these tests will indicate Helicobacter pylori infection (present or past), the role of hereditary factor (intrinsic factor antibody present or absent) and the success or failure of Helicobacter pylori eradication treatment.

Helicobacter pylori link to pernicious anaemia.

An immunological classification of chronic gastritis based on the detection of Helicobacter pylori (H. pylori) antibody, parietal cell antibody, intrinsic factor antibody, is reported. H. pylori chronic gastritis, slowly progresses to atrophic gastritis, in the majority of patients; in a few patients, with genetic susceptibility to form intrinsic factor antibody, it progresses to pernicious anaemia. In majority of patients of pernicious anaemia, H. pylori gradually disappears from the gastric mucosa, on development of intestinal metaplasia in them. Atrophic gastritis results from H. pylori or non H. pylori. H. pylori infection is diagnosed in the presence of H. pylori in the gastric mucosal biopsy and/or H. pylori antibody (IgG) in the serum. The presence of the genetic factor (intrinsic factor antibody) is essential for the diagnosis of pernicious aneamia. Pernicious anaemia patients without intrinsic factor antibody, should be correctly diagnosed as atrophic gastritis, in view of the absence of the genetic factor (intrinsic factor antibody) in them.

Factors responsible for the increasing incidence of oesophageal adenocarcinoma.

Amongst white population of developed countries, the prevalence of oesophageal adenocarcinoma has dramatically increased during the last four decades. During this period, the increased damage to the oesophageal mucosa with gastroesophageal reflux could result from increased acid output (due to absence of Helicobacter pylori in the gastric mucosa with excellent sanitation) and/or increased frequency of reflux due to an "epidemic" of overweight (65% of the population). The most important environmental factors, responsible for the fastest increasing cancer in humans, are discussed.

Summer Temperature and Spatial Variability of all-Cause Mortality in Surat City, India.

BACKGROUND: Ample information is available on extreme heat associated mortality for few Indian cities, but scant literature is available on effect of temperature on spatial variability of all-cause mortality for coastal cities. OBJECTIVE: To assess the effect of daily maximum temperature, relative humidity and heat index on spatial variability of all-cause mortality for summer months (March to May) from 2014 to 2015 for the urban population of Surat (coastal) city. MATERIALS AND METHODS: Retrospective analysis of the all-cause mortality data with temperature and humidity was performed on a total of 9,237 deaths for 184 summer days (2014-2015). Climatic and all-cause mortality data were obtained through Tutiempo website and Surat Municipal Corporation respectively. Bivariate analysis performed through SPSS. OBSERVATIONS: Mean daily mortality was estimated at 50.2 ± 8.5 for the study period with a rise of 20% all-cause mortality at temperature ≥ 40°C and rise of 10% deaths per day during extreme danger level (HI: > 54°C) days. Spatial (Zone wise) analysis revealed rise of 61% all-cause mortality for Southeast and 30% for East zones at temperature ≥ 40°C. CONCLUSIONS: All-cause mortality increased on high summer temperature days. Presence of spatial variation in all-cause mortality provided the evidence for high risk zones. Findings may be helpful in designing the interventions at micro level.

Acquired apolipoprotein B deficiency with chronic hepatitis C virus infection.

Chronic hepatitis C virus (HCV) infection is often associated with fatty liver. Apolipoprotein B (ApoB) deficiency is one of the known causes of fatty liver and acquired ApoB deficiency has recently been reported with HCV infection. We report two patients (47-year-old lady and 48-year-old man) who had asymptomatic transaminase elevation, fatty liver, anti-HCV positive with high viral load (genotype 3). Their lipid profile showed low total cholesterol, low-density lipoprotein, triglycerides and ApoB. One of the patients who received treatment for HCV infection showed improvement in lipid profile and ApoB levels.