Post-vaccination Symptoms of Covishield Vaccine among Frontline Workers of a Tertiary Care Center in Pathanamthitta District.

Introduction: The COVID-19 pandemic, which began in late 2019 and is still ongoing, has affected health and life across the world. Widespread vaccination with highly effective vaccines is an important tool in the efforts to control this pandemic. To determine post-vaccination symptoms after the first dose of Covishield vaccine among health care workers at a tertiary care centre in Pathanamthitta District. Materials and Methods: A descriptive cross-sectional study in a tertiary care hospital in Pathanamthitta District. Data on adverse effects following vaccination with the first dose of Covishield vaccine were collected from health care workers through online surveys and interviews. Baseline characteristics were described with frequency, percentages, and mean. Associations between categorical variables were assessed using the Chi-square test. Results: Of the 1,115 health care workers who participated in the study, the majority were medical students (28.3%), followed by nurses (24.8%), and doctors (19.1%). Post-vaccination symptoms were reported by the majority of the participants (95.1%). The most common symptoms were pain at the site of injection (79.8%), followed by myalgia (67.2%), and tiredness (64.6%). Hospitalization was required for six (0.5%) of the participants. Conclusion: The symptoms reported in the study were those already known to be the general side effects associated with vaccines. The information obtained from this study will aid in health promotion activities related to COVID-19 vaccination.

TTBK2 mutations associated with spinocerebellar ataxia type 11 disrupt peroxisome dynamics and ciliary localization of SHH signaling proteins.

Frameshift mutations in Tau Tubulin Kinase 2 (TTBK2) cause spinocerebellar ataxia type 11 (SCA11), which is characterized by the progressive loss of Purkinje cells and cerebellar atrophy. Previous work showed that these TTBK2 variants generate truncated proteins that interfere with primary ciliary trafficking and with Sonic Hedgehog (SHH) signaling in mice. Nevertheless, the molecular mechanisms underlying the dominant interference of mutations remain unknown. Herein, we discover that SCA11-associated variants contain a bona fide peroxisomal targeting signal type 1. We find that their expression in RPE1 cells reduces peroxisome numbers within the cell and at the base of the cilia, disrupts peroxisome fission pathways, and impairs trafficking of ciliary SMO upon SHH signaling activation. This work uncovers a neomorphic function of SCA11-causing mutations and identifies requirements for both peroxisomes and cholesterol in trafficking of cilia-localized SHH signaling proteins. In addition, we postulate that molecular mechanisms underlying cellular dysfunction in SCA11 converge on the SHH signaling pathway.

Total hip and knee arthroplasty after lower extremity amputation in a military population.

INTRODUCTION: The military includes lower extremity amputees requiring arthroplasty; however, there is little literature on this population. The primary aim of this study was to report demographics and clinical factors in amputees who undergo total hip or knee arthroplasty (THA/TKA) in the Military Health System (MHS). Second, patient-reported outcome measures (PROMs) are reported. METHODS: The Military Data Repository was queried for patients with lower extremity amputations and TKA or THA between 1 October 2014 and 12 October 2020. The medical records were reviewed and patients were contacted to complete PROMs. Mean follow-up for TKA and THA was 5.5 and 2.5 years, respectively. RESULTS: Nineteen TKAs (76%) and eight THAs (28%) were performed in 25 patients. Mean age of TKA and THA patients at the time of arthroplasty was 57 years old. A majority of TKA (68%) and THA (57%) patients underwent amputations secondary to trauma. Nearly all TKAs were performed on the contralateral side to the amputation (95%), while half of THAs were performed on the ipsilateral side (50%). Two THAs (29%) were revised due to periprosthetic fractures, whereas six TKAs (32%) were revised or reoperated on due to infection. Ten TKA patients completed PROMs. The mean score on Knee Osteoarthritis Outcome Score for Joint Replacement (KOOS JR) was 41.8 and Patient-Reported Outcomes Measurement Information System Global-10 (PROMIS-10) was 41.6 (Global Physical Health) and 49.6 (Global Mental Health). CONCLUSIONS: Most TKAs were performed on the contralateral limb, suggesting increased demand on the joint. The most common indication for amputation and post-TKA complication was trauma and infection, respectively. KOOS JR may not accurately capture the outcomes of this population, or they simply do worse. However, PROMIS-10 scores were similar to the non-amputee population, suggesting that the PROMIS-10 may be more useful than the KOOS JR.

Early Clinical and Functional Outcome of Rotator Cuff Tendinopathy of the Shoulder Treated with Platelet Rich Plasma Injection.

INTRODUCTION: Rotator cuff tendinitis has been treated using various methods including physiotherapy, steroid injections and recently platelet rich plasma (PRP). Most of these methods aim at giving symptomatic relief rather than addressing the pathology. There is no clear consensus over the benefit of using PRP for tendinitis. We decided to do a prospective clinical study to demonstrate the efficacy of PRP and study the functional outcome in the treatment of rotator cuff tendinopathy. MATERIAL AND METHODS: Patients with shoulder pain for more than three months not responding to NSAIDs or physiotherapy with a diagnosis of rotator cuff tendinitis, confirmed by MRI, were included in the study. Patients with rotator cuff tear or any other shoulder pathology were excluded. We included a total of 30 patients who received 5ml of landmark guided PRP injection in the subacromial space followed by a six-week exercise program. Patients were followed-up at 3, 6 and 12 weeks. and were assessed clinically using the VAS, SPADI and Constant and Murley Score. RESULTS: VAS score of patients improved from a pre injection score of 7.4 to a score of 1.9 in the 12th week. The mean SPADI score and Constant score improved from a pre injection score of 73.33 and 39.57 to a post injection score of 18.1 and 86.47, respectively. CONCLUSION: Platelet Rich Plasma injections showed good to excellent early results, in patients with rotator cuff tendinopathy with improvement in VAS, SPADI and Constant scores.

PI3Kγ is a molecular switch that controls immune suppression.

Macrophages play critical, but opposite, roles in acute and chronic inflammation and cancer. In response to pathogens or injury, inflammatory macrophages express cytokines that stimulate cytotoxic T cells, whereas macrophages in neoplastic and parasitic diseases express anti-inflammatory cytokines that induce immune suppression and may promote resistance to T cell checkpoint inhibitors. Here we show that macrophage PI 3-kinase γ controls a critical switch between immune stimulation and suppression during inflammation and cancer. PI3Kγ signalling through Akt and mTor inhibits NFκB activation while stimulating C/EBPß activation, thereby inducing a transcriptional program that promotes immune suppression during inflammation and tumour growth. By contrast, selective inactivation of macrophage PI3Kγ stimulates and prolongs NFκB activation and inhibits C/EBPß activation, thus promoting an immunostimulatory transcriptional program that restores CD8+ T cell activation and cytotoxicity. PI3Kγ synergizes with checkpoint inhibitor therapy to promote tumour regression and increased survival in mouse models of cancer. In addition, PI3Kγ-directed, anti-inflammatory gene expression can predict survival probability in cancer patients. Our work thus demonstrates that therapeutic targeting of intracellular signalling pathways that regulate the switch between macrophage polarization states can control immune suppression in cancer and other disorders.

Macrophage PI3Kγ Drives Pancreatic Ductal Adenocarcinoma Progression.

UNLABELLED: Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with a low 5-year survival rate, yet new immunotherapeutic modalities may offer hope for this and other intractable cancers. Here, we report that inhibitory targeting of PI3Kγ, a key macrophage lipid kinase, stimulates antitumor immune responses, leading to improved survival and responsiveness to standard-of-care chemotherapy in animal models of PDAC. PI3Kγ selectively drives immunosuppressive transcriptional programming in macrophages that inhibits adaptive immune responses and promotes tumor cell invasion and desmoplasia in PDAC. Blockade of PI3Kγ in PDAC-bearing mice reprograms tumor-associated macrophages to stimulate CD8(+) T-cell-mediated tumor suppression and to inhibit tumor cell invasion, metastasis, and desmoplasia. These data indicate the central role that macrophage PI3Kγ plays in PDAC progression and demonstrate that pharmacologic inhibition of PI3Kγ represents a new therapeutic modality for this devastating tumor type. SIGNIFICANCE: We report here that PI3Kγ regulates macrophage transcriptional programming, leading to T-cell suppression, desmoplasia, and metastasis in pancreas adenocarcinoma. Genetic or pharmacologic inhibition of PI3Kγ restores antitumor immune responses and improves responsiveness to standard-of-care chemotherapy. PI3Kγ represents a new therapeutic immune target for pancreas cancer. Cancer Discov; 6(8); 870-85. ©2016 AACR.This article is highlighted in the In This Issue feature, p. 803.

Bruton Tyrosine Kinase-Dependent Immune Cell Cross-talk Drives Pancreas Cancer.

UNLABELLED: Pancreas ductal adenocarcinoma (PDAC) has one of the worst 5-year survival rates of all solid tumors, and thus new treatment strategies are urgently needed. Here, we report that targeting Bruton tyrosine kinase (BTK), a key B-cell and macrophage kinase, restores T cell-dependent antitumor immune responses, thereby inhibiting PDAC growth and improving responsiveness to standard-of-care chemotherapy. We report that PDAC tumor growth depends on cross-talk between B cells and FcRγ(+) tumor-associated macrophages, resulting in T(H)2-type macrophage programming via BTK activation in a PI3Kγ-dependent manner. Treatment of PDAC-bearing mice with the BTK inhibitor PCI32765 (ibrutinib) or by PI3Kγ inhibition reprogrammed macrophages toward a T(H)1 phenotype that fostered CD8(+) T-cell cytotoxicity, and suppressed PDAC growth, indicating that BTK signaling mediates PDAC immunosuppression. These data indicate that pharmacologic inhibition of BTK in PDAC can reactivate adaptive immune responses, presenting a new therapeutic modality for this devastating tumor type. SIGNIFICANCE: We report that BTK regulates B-cell and macrophage-mediated T-cell suppression in pancreas adenocarcinomas. Inhibition of BTK with the FDA-approved inhibitor ibrutinib restores T cell-dependent antitumor immune responses to inhibit PDAC growth and improves responsiveness to chemotherapy, presenting a new therapeutic modality for pancreas cancer.

Variant Guillain-Barré Syndrome in a Patient with Non-Hodgkin's Lymphoma.

We report a 72-year-old female patient with diffuse large B cell non-Hodgkin's lymphoma (NHL) with previous treatment with standard chemotherapy presenting as an acute, ascending, sensorimotor polyneuropathy. Nerve conduction studies and lumbar puncture supported a rare, but ominous, axonal variant of Guillain-Barré Syndrome (GBS) known as acute motor and sensory axonal neuropathy (AMSAN), which is distinguished from the more common, acute demyelinating forms of GBS. Previous reports have largely focused on toxicities secondary to chemo- or radiotherapy as a major contributor to the development of acute neuropathies in malignancy. Clinicians should also be mindful of direct neoplastic invasion or, less commonly, paraneoplastic phenomenon, as alternative mechanisms, the latter possibly reflecting immune dysregulation in particularly aggressive lymphomas. At the time of writing, this is the first report in the literature of an axonal variant of GBS in a patient with diffuse large B cell NHL. A discussion regarding common and uncommon neuropathies in haematological malignancies is made, with a brief review of the anecdotal evidence supporting a paraneoplastic association with GBS or its variant forms in the setting of lymphoma.

Invariant natural killer T cells in children with eosinophilic esophagitis.

BACKGROUND: Eosinophilic esophagitis (EoE) is an atopic disease characterized by eosinophilic inflammation in which dietary antigens (in particular, milk) play a major role. EoE is most likely a mixed IgE and non-IgE food-mediated reaction in which overexpression of Th2 cytokines, particularly IL-13, play a major role; however, the cells responsible for IL-13 overexpression remain elusive. Th2-cytokines are secreted following the ligation of invariant natural killer T cell receptors to sphingolipids (SLs). Sphingolipids (SLs) are presented via the CD1d molecule on the INKTs surface. Cow's milk-derived SL has been shown to activate iNKTs from children with IgE-mediated food allergies to milk (FA-MA) to produce Th2 cytokines. The role of iNKTs and milk-SL in EoE pathogenesis is currently unknown. OBJECTIVE: The aim of this study was to investigate the role of iNKTs and milk-SL in EoE. METHODS: Peripheral blood mononuclear cells (PBMCs) from 10 children with active EoE (EoE-A), 10 children with controlled EoE (EoE-C) and 16 healthy controls (non-EoE) were measured ex vivo and then incubated with α-galactosylceramide (αGal) and milk-SL. INKTs from peripheral blood (PB) and oesophageal biopsies were studied. RESULTS: EoE-A children had significantly fewer peripheral blood iNKTs with a greater Th2-response to αGal and milk-SM compared with iNKTs of EoE-C and non-EoE children. Additionally, EoE-A children had increased iNKT levels in oesophageal biopsies compared with EoE-C children. CONCLUSION: Milk-SLs are able to activate peripheral blood iNKTs in EoE-A children to produce Th2 cytokines. Additionally, iNKT levels are higher at the site of active oesophageal eosinophilic inflammation. CLINICAL RELEVANCE: This study suggests that sphingolipids (SLs) contained in milk may drive the development of EoE by promoting an iNKT-cell-mediated Th2-type cytokine response that facilitates eosinophil-mediated allergic inflammation.

Sexual dysfunction among men in secondary care in southern India: Nature, prevalence, clinical features and explanatory models.

BACKGROUND: Sexual dysfunction, common in general medical practice, is under-recognized and inadequately managed resulting in significant morbidity and reduction in quality of life. We examined the nature, prevalence, clinical features and explanatory models of illness among men with sexual dysfunction in a general healthcare setting. METHODS: We recruited 270 consecutive men attending a general health clinic. Participants were evaluated using a structured interview. The International Index of Erectile Function-5, the Chinese Index of Premature Ejaculation-5, Short Explanatory Model Interview and the Revised Clinical Interview Schedule were used to assess sexual dysfunction, explanatory models and psychiatric morbidity. RESULTS: Premature ejaculation and erectile dysfunction were reported by 43.0% and 47.8% of men, respectively. The most common perceived causes were loss of semen due to masturbation and nocturnal emission. Popular treatments were herbal remedies and resources used were traditional healers. The factors associated with erectile dysfunction were diabetes mellitus, financial stress, past history of psychiatric treatment and common mental disorders such as depression and anxiety; those associated with premature ejaculation were common mental disorders, older age and financial debt. Sexual dysfunctions and concerns were under-diagnosed by physicians when compared to the research interview. CONCLUSION: There is a need to recognize sexual problems and effectively manage them in general medical settings. The need for sex education in schools and through the mass media, to remove sexual misconceptions, cannot be under-emphasized.

Multiple populations of artemisinin-resistant Plasmodium falciparum in Cambodia.

We describe an analysis of genome variation in 825 P. falciparum samples from Asia and Africa that identifies an unusual pattern of parasite population structure at the epicenter of artemisinin resistance in western Cambodia. Within this relatively small geographic area, we have discovered several distinct but apparently sympatric parasite subpopulations with extremely high levels of genetic differentiation. Of particular interest are three subpopulations, all associated with clinical resistance to artemisinin, which have skewed allele frequency spectra and high levels of haplotype homozygosity, indicative of founder effects and recent population expansion. We provide a catalog of SNPs that show high levels of differentiation in the artemisinin-resistant subpopulations, including codon variants in transporter proteins and DNA mismatch repair proteins. These data provide a population-level genetic framework for investigating the biological origins of artemisinin resistance and for defining molecular markers to assist in its elimination.

Aligning community engagement with traditional authority structures in global health research: a case study from northern Ghana.

Despite the recognition of its importance, guidance on community engagement practices for researchers remains underdeveloped, and there is little empirical evidence of what makes community engagement effective in biomedical research. We chose to study the Navrongo Health Research Centre in northern Ghana because of its well-established community engagement practices and because of the opportunity it afforded to examine community engagement in a traditional African setting. Our findings suggest that specific preexisting features of the community have greatly facilitated community engagement and that using traditional community engagement mechanisms limits the social disruption associated with research conducted by outsiders. Finally, even in seemingly ideal, small, and homogeneous communities, cultural issues exist, such as gender inequities, that may not be effectively addressed by traditional practices alone.

Cytological damage of nasal epithelium associated with decreased glutathione peroxidase in residents from a heavily polluted city.

OBJECTIVE: To evaluate the cytological damage and glutathione peroxidase (GPX) content in the nasal epithelium of residents of Southwest Metropolitan Mexico City (SWMMC) along 1 year of ozone and PM(10) exposure. METHOD: Four nasal scrapings were obtained in 20 volunteers from a control low polluted city and SWMMC permanent residents (n = 20) during 1 year. The scrapings were obtained in September and December 2004, and February and May 2005. One part of the scraping was stained by hematoxylin-eosin technique for cytological evaluation and a second part was stained by immunocytochemistry method to evaluate GPX concentration by morphometry. RESULTS: Control subjects: in total, 30% had no cytological alterations and 70% showed only mild or moderate inflammation in four nasal scrapings. All SWMMC residents showed moderate to severe inflammatory processes in some scrapings. Additionally, dysplasia was found once (in 2 cases) or more than on scraping in five cases (25%). GPX concentration in the control group remained highest in median values throughout the study. SWMMC residents with the highest median values of GPX content were found in the May and September scrapings, and the lowest median values were found in December and February when Ozone and PM(10) levels are increased (P < or = 0.05). A lower GPX content was found as the cytological damage increased (P < or = 0.001). CONCLUSION: Cytological evaluation of nasal epithelium and GPX immunodetection are satisfactory methods to evaluate the earliest damage produced by atmospheric pollution in heavily contaminated cities.

A tale behind the rectum.

Tailgut cysts, also called benign retrorectal hamartomas, are uncommon developmental cysts found behind the rectum. Here, we present a rare case of a tailgut cyst associated with uterine anomaly, sacral and vertebral anomalies and vascular duplication, in a young lady who presented with constipation and infertility.

Rates and factors associated with suicide in Kaniyambadi Block, Tamil Nadu, South India, 2000-2002.

BACKGROUND: Inefficient civil registration systems, non-report of deaths, variable standards in certifying death and the legal and social consequences of suicide are major obstacles to investigating suicide in the developing world. OBJECTIVE: The aim of this study was to prospectively determine the suicide rate in Kaniyambadi Block, Tamil Nadu, South India, for the years 2000-2002 using verbal autopsies. METHOD: The setting for the study was a comprehensive community health programme in a development block in rural South India. The main outcome measure was death by suicide, diagnosed by a detailed verbal autopsy and census, and birth and death data to identify the population base. RESULTS: The average suicide rate was 92.1 per 100,000. The ratio of male to female suicides was 1:0.66. The age-specific suicide rate for men increased with age while that for women showed two peaks: 15-24 years and over 65 years of age. Hanging (49%) and poisoning with organo-phosphorus compounds (40.5%) were the commonest methods of committing suicide. Acute and/or chronic stress was elicited for nearly all subjects. More men suffered from chronic stress while more women had acute precipitating events (chi2 = 4.58; p < 0.04). People less than 44 years of age had more acute precipitating events before death while older subjects reported more chronic stress (chi2 = 17.38; p < 0.001). CONCLUSION: The study replicates findings of an earlier study from the area. The suicide rate documented in this study is very high and is a major public health concern. There is a need for sentinel centres in India and in developing countries to monitor trends and to develop innovative strategies to reduce deaths by suicide.

Solar disinfection of water for diarrhoeal prevention in southern India.

AIMS: To evaluate the efficacy and acceptability of solar irradiation in the prevention of diarrhoeal morbidity in children under 5 years of age, in an urban slum in Vellore, Tamil Nadu. METHODS: A total of 100 children were assigned to receive drinking water that had been subjected to solar disinfection in polyethylene terephthalate bottles. One hundred age and sex matched controls were also selected. Both groups were followed by weekly home visits for a period of six months for any diarrhoeal morbidity. At the end of the follow up period, the acceptability of the intervention was assessed by interviews, questionnaires, and focus group discussions. RESULTS: There was significant reduction in the incidence, duration, and severity of diarrhoea in children receiving solar disinfected water, despite 86% of the children drinking water other than that treated by the intervention. The incidence of diarrhoea in the intervention group was 1.7 per child-year, and among controls 2.7 per child-year, with an incidence rate ratio of 0.64 (95% CI -0.48 to 0.86). The risk of diarrhoea was reduced by 40% by using solar disinfection. In qualitative evaluation of acceptability, most women felt that solar disinfection was a feasible and sustainable method of disinfecting water. CONCLUSIONS: Solar disinfection of water is an inexpensive, effective, and acceptable method of increasing water safety in a resource limited environment, and can significantly decrease diarrhoeal morbidity in children.