“Elucidation of the Shared Pathophysiology between Diabetes and COVID-19”

Background: COVID-19 is a rapidly spreading communicable disease worldwide. It varies widely in its spectrum of manifestations, from being mild self-limiting disease, to fulminant disease, often leading to complications and death. Diabetes is an important co-morbidity linked to severity of infection by SARSCoV- 2, which predisposes them to severe pneumonia. Poor glycaemic control is associated with worse outcomes. The disease burden of COVID-19 is continuously increasing, and with a high prevalence of diabetes, it is all the more important to understand the vital aspects of COVID-19 infection in diabetic population. Hence, we try to provide close insights into its pathophysiology, clinical characteristics, recommendations on management and prevention and possible avenues for improving disease outcomes. Methods: PubMed database and Google Scholar were searched using the key terms ‘COVID-19’, ‘SARS CoV- 2’, ‘Corona’ and ‘diabetes’. Full texts of the retrieved articles were accessed and referred. Three main mechanisms which influence COVID-19 disease manifestation in diabetics include: (a) Entry of virus via ACE-2 receptors (b) Action through Dipeptidyl-peptidase-4, and (c) Elevation of glucose concentration in airways by elevated blood glucose.ACE-2 is expressed in alveolar epithelial cells, heart, renal-tubular and intestinal epithelia and pancreas. S-Glycoprotein on the surface of SARS-CoV-2 binds to this ACE-2 and undergoes a conformational change. This allows its’ proteolytic digestion by host cell proteases TMPRSS2 and Furin, leading to internalization of virus. Viral entry into cells triggers an inflammatory response by T-helper-cells and at times, a ‘cytokine storm’, resulting in organ damage. Apart from diminishing neutrophil chemotaxis and reducing phagocytosis, by which diabetes predisposes individuals to infections, there are several specific factors with respect to SARS-CoV2: (i) Increased ACE-2 expression (ii) Raised Furin (iii) Diminished T-cell functioning, and (iv) Increased IL-6 levels. Movement restrictions, increased stress due to social isolation and lack of physical activity further complicates the issue. It is therefore, much essential to raise awareness among front-line workers. Finally, the current situation emphasizes the need for more clinical investigation and define best practices for optimum outcomes. Bangladesh Journal of Medical Science Vol. 21(1) 2022 Page : 19-23

Excess consumption of Lavana Rasa (Salty taste) – A cause of Amlapitta (Hyperacidity)

Amlapitta (Hyperacidity) is one of the ever growing diseases observed in society. Intake of salt in excess can lead into Amlapitta due to its Vidahi and Agneya property. Foods like cheese, chips, sauces, buttermilk, etc. contains variety of salts including common salt. The disease Amlapitta/ Amlika can be interpreted as Hyperacidity; is not separately described in Samhita, but mentioned as Lakshana (symptom) of Atiyoga (excessive intake) of Lavana Rasa. Hence an observational study was designed. Aim: To examine whether Atiyoga of Lavana Rasa (common salt) can be a Hetu (causative factor) of Amlapitta. Methodology: Study included 100 identified patients of Amlapitta; both males and females from the age group of 20-60 years suffering from Amlodgar (sour blenching) as the predominant symptom. A structured, pilot tested 6 item questionnaire was used to collect data. Statistical Analysis: Descriptive data was analyzed using number and percentage. Results: Maximum patients were from 20-29 years age group; with Kapha-Pittaja Prakruti (77.78 %) and Pitta-Kaphaja Prakruti (68.75%) who used to consume Lavana rasa in variety of type and in excess quantity. Family history of the disease Amlapitta showed maximum % in female patients as 31.03% whereas only 4.76% males suffered from the disease. Liking towards Lavana, Katu and Amla rasa in population was found to be 36%, 28%, 16% respectively. In causative factors of Amlapitta, Lavana Rasadhikya was noted in 62 patients whereas Vidahi Anna followed by spicy food and oily food was found in 60, 58, 56 number of patients respectively. Conclusion: From the study, it is observed that there is proneness of Amlapitta mostly in age group 20-29 years having liking towards salty, spicy and Katu Rasa. Maximum (58) female patients, with 31.03% who had family history of Amlapitta and 77.78% patients found to have Kapha-Pitta dominent Prakruti which indicate towards importance of Prakriti and family history of an individual in disease manifestation.

Evaluation of the Knowledge of Saudi Women in Childbearing Period towards Toxoplasmosis Induced Teratogenicity – Evidence from A Cross-Sectional Study

Background: Toxoplasmosis is an environmental teratogen that may disrupt fetal development if transferred to the mother during pregnancy, resulting in maldevelopment and newborn mortality. Objective: To assess knowledge of Saudi women in their childbearing period as regards risk factors of Toxoplasmosis infestation, testing, awareness of disease manifestation and prevention. Methods: Anonymous online survey was used to examine the knowledge of Saudi women in their childbearing period about Toxoplasmosis induced teratogenicity. The non-probability sampling yields a calculated size of 600 women. The cross-sectional design of the research required categorizing the questions into two significant portions, one for sociodemographic data and the other for assessing Toxoplasmosis awareness. First, a descriptive statistic summarized the demographic characteristics. In categorical data, chi-square tests were employed to compare groups. Results: A total of 613 women in their childbearing years completed the questionnaire. Most respondents interviewed were 36-40 (46.7%), and Para 1-5 (80%), and 86% were graduates. In addition, 42.2 % had the basic knowledge of Toxoplasmosis, 25.3 % were aware of the manifestations of the disease, and 76.3% correctly identified premature labor or miscarriage as sequelae of the infection. Aside from the frequency of abnormalities and parities and knowledge of toxoplasmosis, no other demographics in our research sample showed a significant association. Conclusion: The basic knowledge of Toxoplasmosis among Saudi women of childbearing age is unsatisfactory (42.6 %). Age, family income, educational level and the number of abortions were significantly associated with knowledge of Toxoplasmosis among Saudi women in their childbearing age.

Real world practice of medical treatment for moderate and severe inflammatory bowel diseases in Russian Federation, Republic of Belarus and Republic of Kazakhstan: intermediate results of the INTENT study

Background: The analysis of data obtained from real world clinical practice of management of patients with inflammatory bowel diseases (IBD) is an effective tool to improve medical care for this patient category. Studies of the kind are rare in Russia, which hinders a critical assessment of the current situation and optimization of the established approaches.Aim: To study real world practice of medical treatment of patients with moderate and severe IBD in the Russian Federation, Republic of Belarus and Republic of Kazakhstan.Materials and methods: We analyzed intermediate results from the INTENT study (NCT03532932), which is a multinational, multicenter, retrospective and prospective, non-interventional observation trial being performed in the Russian Federation, Republic of Belarus and Republic of Kazakhstan. The retrospective analysis included data from 706 patients above 18 years of age with confirmed diagnosis of moderate/severe ulcerative colitis (UC) and Crohn's disease (CD) made at least 2 years before the study entry, with acute exacerbations of the disease at the study entry or within the last 2 years. Data were collected during routine management; at the study entry the patients were treated with a standard regimen including 5-aminosalicylic acid (5-ASA) agents, glucocorticosteroids (GCS) and immunosuppressants (IS), as well as genetically engineered biological agents (GEBA).Results: Among 706 IBD patients, 465 had UC and 241 had CD. The male to female ratios in both groups were similar. Mean age of the UC patients was higher than that of the CD patients (41.8 [95% confidence interval (CI) 40.6–43.0] years vs 35.6 [95% CI 33.9–37.3] years, p = 0.0001). The same difference was noted for the mean age of disease manifestation (34.5 [95% CI 33.29–35.61] vs 29.7 [95% CI 28.03–31.3] years, p = 0.0001) and for mean duration of disease from the time of diagnosis to the study entry (7.3 [95% CI 6.77–7.9] for UC and 5.9 [95% CI 5.3–6.59] years for CD, p = 0.0027). The proportion of patients with familial history of IBD was low (3.2 and 0.8%, respectively, p = 0.0672). The number of smokers with CD was more than 2-fold higher than those with UC (11.2% vs 5%, p < 0.001). 58.1% of the patients in the UC group and 47.0% of those from the CD group were employed (р < 0.05). 36.6% of the UC patients and 56.0% of the CD patients had the legal disability status due to underlying disease (p < 0.005).The relapsing course of the disease was noted in 72.9% with UC and 60.6% with CD, while in the rest of the patients the disease had the continuous course. The degree of UC involvement corresponded to pancolitis in 58.9% of the cases, to left-sided colitis in 33.1%, and to proctitis in 8%. The distribution of CD location was as follows: ileocolitis 54.8%, terminal ileitis 23.7%, colitis 20.3%, isolated upper gastrointestinal tract involvement 1.2%. The prevalence of complicated UC was 12.9%, and that of the complicated CD 57.4% (р = 0.0001). There were no difference in the rate of extraintestinal manifestations between UC and CD (23.4 and 28.2%, respectively, p = 0.1705).UC and CD groups differed by their treatment patterns. In the UC group, 5-ASA + GCS regimens were given to 25.4% of the patients, whereas in the CD group, to 3.7% (р ≤ 0.0001). The second frequent regimens were: 5-ASA with subsequent IS ± GCS (17.9% in UC, 22.8% in CD, p = 0.1331); standard regimen (any 5-ASA agent, IS or GCS, but not GEBA) with subsequent treatment withdrawal or its reduction to GCS monotherapy (14.8% in UC, 5% in CD, р = 0.0001); 5-ASA with a subsequent combination with IS, then any tumor necrosis factor-α inhibitor (iTNF-α) as the basic treatment with continuation of 5-ASA and/or IS (22% in CD vs 13.5% in UC, р = 0.0052); treatment initiation from iTNF-α combined with any standard agent without any subsequent modification (24.1% in CD and 13.6% in UC, р = 0.0007). Less frequent the following treatment regimens were used: initial treatment with 5-ASA and subsequent iTNF-α with continuation of 5-ASA (4.5% in UC and 2.5% in CD, р = 0.2181); initial treatment with iTNF-α in combination with any standard agent with subsequent GEBA withdrawal and continuation of a standard regimen or its withdrawal (4.3% in UC and 7.5% in CD, р = 0.0812).The cumulative frequency of GEBA administration at various stages of treatment for CD (66.4%) was significantly higher than for UC (39.4%). Vedolizumab for CD was administered more frequently than for UC (10.4 and 3.4%, respectively, p = 0.0003). The analysis of habitual GCS use revealed a number of negative trends, namely, half of the IBD patients received more than 2 GCS courses within 2 years, and in some cases the number of GCS courses amounted to 5–8. Mean duration of a GCS course in most regimens for UC and CD was in the range of 91 to 209 days, which is significantly higher than the recommended treatment duration of 12 weeks (83 days).Conclusion: With a number of its demographic characteristics and clinical particulars, the study cohort of patients with IBD is compatible to global trends: the male to female ratio, mean patients’ age, young age at disease manifestation, smoking status, prevalence of extraintestinal manifestations and the location of CD. It is of note that 5-ASA is included into almost all treatment regimens for CD, which does not meet the treatment strategy recommended in the guidelines. Frequent administration and long duration of GCS therapy also is in contradiction with the guidelines. Of significant concern is rather rare and late administration of GEBA, especially for UC. We believe that the identified pitfalls are associated both with low awareness of doctors on the current strategies of IBD management and with low patients' compliance to treatment.

A CASE OF CERVICAL INTRAEPITHELIAL NEOPLASIA - MANAGEMENT THROUGH AYURVEDA

Introduction – Cervical cancer is the 2nd most leading prevalent cancer in India. There are an estimated 123,000 new cases of cervical cancer in India every year with 67,000 deaths in women alone. Cervical cancer in Recent studies shows that screening of cervical cancer reduces the disease incidence and disease mortality by 50%. Low- grade squamous intraepithelial lesion (LSIL) is a common abnormal result on a Pap smear cervical test. It’s also known as mild dysplasia. Methodology – Here is a case report of a patient aged 26yrs with complaints of white discharge per vagina with severe itching, on routine cervical screening investigations found to have Low grade squamous intraepithelial neoplasms. She was treated with Ayurvedic sthanika chikitsa (Local therapies) such as Yoni prakshalana (Vaginal douching), and Yoni pichu (Vaginal tamponing) for 7 days along with shaman chikitsa. Later PAP smear was repeated after 1 month of follow up and found to have negative for intraepithelial neoplasia. And there was relief in the symptoms following treatment. Results- In this case, there was a relief of symptoms and on follow up when Pap smear was repeated, there was negative for intraepithelial neoplasia. Ayurvedic treatment modalities such as Sthanika chikitsa which includes yoni prakshalana and Yoni Pichu are the line of treatment for various gynecological problems and help in reducing mortality and morbidity caused due to cervical cancer in India. Discussion- Here Low-grade squamous Intraepithelial neoplasia can be considered as the Sanchaya avastha and hence diagnosing the disease in its Sanchaya avastha i.e mild dysplasia, is important. During Sanchaya avastha there is localized neoplastic changes of cervical cells and there is Manifestation of Low-grade Intraepithelial Neo- plasia. In the later stages of Kriyakala (Stages of disease manifestation) the neoplasia turns into metastasis and further differentiation occurs which Manifests all the symptoms of Cervical Cancer. Hence treatment modalities such as Yoni prakshalana and yoni pichu helps in preventing later conditions such as cervical cancer. Keywords: Cervical Cancer, LSIL, Ayurveda, Sanchaya

Diagnostic criteria for spinal muscular atrophy 5q

Background. The variety of phenotypic manifestations of spinal muscular atrophy 5q (5qCMA) is the reason for the difficulty in diagnosing and delaying the diagnosis, which is of particular importance today due to the emergence of new etiopathogenetic therapeutic possibilities.Objective: determination of the main clinical features and symptoms of 5qCMA with onset at different age periods, and the development of an algorithm that can help in making decisions regarding the need for testing the SMN1 gene by primary care and hospital doctors.Materials and methods. A retrospective analysis of the case histories of patients observed at the Research Center of Medical Genetics with a confirmed diagnosis of 5qCMA was carried out.Results. The study included data from 315 patients, including: 173 with type I, 95 and 47 with types II and III 5qCMA. In all cases, the presence and diagnostic significance of 27 signs and symptoms were analyzed, depending on the age of disease manifestation. An attempt was made to isolate the main symptoms, which are the basis for the mandatory exclusion of 5qCMA by molecular genetic methods in patients with the onset of the disease before and after 18 months of life.

TBK1 recruitment to STING mediates autoinflammatory arthritis caused by defective DNA clearance

Defective DNA clearance in DNase II−/− mice leads to lethal inflammatory diseases that can be rescued by deleting cGAS or STING, but the role of distinct signaling pathways downstream of STING in the disease manifestation is not known. We found that the STING S365A mutation, which abrogates IRF3 binding and type I interferon induction, rescued the embryonic lethality of DNase II−/− mice. However, the STING S365A mutant retains the ability to recruit TBK1 and activate NF-κB, and DNase II−/−STING-S365A mice exhibited severe polyarthritis, which was alleviated by neutralizing antibodies against TNF-α or IL-6 receptor. In contrast, the STING L373A mutation or C-terminal tail truncation, which disrupts TBK1 binding and therefore prevents activation of both IRF3 and NF-κB, completely rescued the phenotypes of DNase II−/− mice. These results demonstrate that TBK1 recruitment to STING mediates autoinflammatory arthritis independently of type I interferons. Inhibiting TBK1 binding to STING may be a therapeutic strategy for certain autoinflammatory diseases instigated by self-DNA.

High-Resolution Computed Tomography Based Comparative Analysis of Asbestosis vs. Fibrotic Hypersensitivity Pneumonitis

BackgroundAsbestosis and fibrotic hypersensitivity pneumonitis (FHP) are fibrotic interstitial lung diseases that develop secondary to inhalation exposure. The differential diagnosis is based on clinical evaluation of imaging findings, particularly in developing countries. We compared the imaging features between asbestosis and FHP to gain a better understanding of the differential diagnostic value of these conditions.MethodsThis comparative study included 204 patients with asbestosis and 74 patients with FHP. We compared patients’ clinical data and chest high-resolution computed tomography (HRCT) images obtained from a predesigned chart. The International Classification of HRCT for Occupational and Environmental Respiratory Diseases was used to categorize chest imaging findings in patients. Diagnostic tests were used to compare the imaging features of asbestosis and FHP.ResultsPatients with asbestosis were older and had a longer latent period until disease manifestation than those with FHP. Asbestosis was characterized by irregular and/or linear opacities, with lower lung preponderance, accompanied by ground-glass opacities and mosaic attenuation. Notably, 98.5% of patients with asbestosis showed benign pleural abnormalities, and >33% of these patients had diffuse pleural thickening with parenchymal bands and/or rounded atelectasis. Abnormalities of the mediastinal and diaphragmatic pleura were observed only in cases of asbestosis, and this finding showed high specificity for the diagnosis for asbestosis compared with that for FHP. Subpleural dots or diaphragmatic pleural abnormalities showed moderate sensitivity and high specificity for diagnosis of asbestosis compared with that for FHP. Interobserver reliability was good for evaluation of imaging findings including honeycombing, pleural calcification, lymphadenectasis, and lymph node calcification.ConclusionsHRCT-based imaging findings can distinguish between asbestosis and FHP to a certain extent, particularly with regard to subpleural dots and diaphragmatic pleural abnormalities that characterize the former.

Chikungunya virus infection: molecular biology, clinical characteristics, and epidemiology in Asian countries

Chikungunya virus (CHIKV) is a re-emerging mosquito-borne human pathogen that causes chikungunya fever, which is typically accompanied by severe joint pain. In Asia, serological evidence indicated that CHIKV first emerged in 1954. From the 1950’s to 2005, sporadic CHIKV infections were attributed to the Asian genotype. However, the massive outbreak of CHIKV in India and the Southwest Indian Ocean Islands in 2005 has since raised chikungunya as a worldwide public health concern. The virus is spreading globally, but mostly in tropical and subtropical regions, particularly in South and Southeast Asia. The emergence of the CHIKV East/Central/South African genotype-Indian Ocean lineage (ECSA-IOL) has caused large outbreaks in South and Southeast Asia affected more than a million people over a decade. Notably, the massive CHIKV outbreaks before 2016 and the more recent outbreak in Asia were driven by distinct ECSA lineages. The first significant CHIKV ECSA strains harbored the Aedes albopictus-adaptive mutation E1: A226V. More recently, another mass CHIKV ECSA outbreak in Asia started in India and spread beyond South and Southeast Asia to Kenya and Italy. This virus lacked the E1: A226V mutation but instead harbored two novel mutations (E1: K211E and E2: V264A) in an E1: 226A background, which enhanced its fitness in Aedes aegypti. The emergence of a novel ECSA strain may lead to a more widespread geographical distribution of CHIKV in the future. This review summarizes the current CHIKV situation in Asian countries and provides a general overview of the molecular virology, disease manifestation, diagnosis, prevalence, genotype distribution, evolutionary relationships, and epidemiology of CHIKV infection in Asian countries over the past 65 years. This knowledge is essential in guiding the epidemiological study, control, prevention of future CHIKV outbreaks, and the development of new vaccines and antivirals targeting CHIKV.