India faces multiple major challenges on the COVID-19 front. It is densely populated: 464 people/km2 compared with Italy’s 206, Spain’s 91, Iran’s 52 and the USA’s 36. It has a huge population: 1380 million (USA 330 million, Iran 83 million, Italy 60 million, Spain 46 million). Social distancing without total shutdowns is unthinkable, especially in the big cities with crowded streets, trains, buses and offices. Cough hygiene is largely absent. Hand hygiene is equally suspect. The latest data from...
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BackgroundThe association between pulse pressure (PP) and the risk of first ischaemic stroke (IS) is inconsistent. Therefore, we evaluated the association between PP and the risk of first IS among elderly hypertensive population in China.MethodsThis was a retrospective cohort study. Patients with hypertension and aged ≥60 years were recruited. Multivariate Cox regression was performed to evaluate the association between PP and the risk of IS. We further stratified the regression models into subgroups...
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I was interested to read the abstract of a recent systematic review and meta-analysis, published in the Postgraduate Medical Journal, which concluded: "The review suggests that acupuncture is an effective therapy for simple obesity rather than a placebo effect. This potential benefit needs to be further evaluated by longer-term and more rigorous RCTs".1 Whilst I must commend the authors for attempting to progress our understanding of potential therapies for the treatment of obesity in adults, I have...
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An 89-year-old woman was brought to the emergency department, responding only to pain (GCS 6), with a rectal temperature of 28.5°C, hypotension (68/40), bradycardia (35/min) and bradypnoea. The remainder of the examination was unremarkable.She was living at home with her son and a caretaker, confined to bed/wheelchair with a history of Alzheimer’s dementia, falls, hypothyroidism (on replacement), hypertension and chronic atrial fibrillation (AF) (on amlodipine 5 mg four times a day, propranolol 10...
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Until Ayushman Bharat, India’s biggest experiment with public health insurance was the Rashtriya Swasthya Bima Yojana (RSBY), literally translated from Hindi as ‘National Health Insurance Program’. Until its launch in 2008, nothing of this magnitude had been attempted. Ayushman Bharat is widely considered a large-scale upgrade of RSBY. The Government of India, on its official website, india.gov.in, the National Portal of India, has had the humility to publicly admit to the failure of past efforts...
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ObjectivesJunior doctors are frequently exposed to occupational and traumatic stress, sometimes with tragic consequences. Mindfulness-based and fitness interventions are increasingly used to mitigate this, but have not been compared.We conducted a randomised, controlled pilot trial to assess the feasibility, acceptability and effectiveness of these interventions in junior doctors.MethodsWe randomised participants (n=21) to weekly 1-hour sessions of personalised, trauma-informed yoga (n=10), with...
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Adipose tissue inflammation has been proposed as a critical link between obesity and metabolic diseases, such as type 2 diabetes and cardiovascular diseases. In obese adipose tissue, macrophages and other immune cells are accumulated, triggering chronic inflammation. Elevated proinflammatory immune cells not only dysregulate adipose tissue function but also subsequently elicit systemic inflammation through the production of inflammatory mediators. Particularly, inflammatory cytokines from adipose...
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Peptidoglycan, the sugar-amino acid polymer that composes the bacterial cell wall, requires a significant expenditure of energy to synthesize and is highly immunogenic. To minimize the loss of an energetically expensive metabolite and avoid host detection, bacteria often recycle their peptidoglycan, transporting its components back into the cytoplasm, where they can be used for subsequent rounds of new synthesis. The peptidoglycan-recycling substrate binding protein (SBP) MppA, which is responsible...
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Staphylococcus aureus is a noted human and animal pathogen. Despite decades of research on this important bacterium, there are still many unanswered questions regarding the pathogenic mechanisms it uses to infect the mammalian host. This can be attributed to it possessing a plethora of virulence factors and complex virulence factor and metabolic regulation. PurR, the purine biosynthesis regulator, was recently also shown to regulate virulence factors in S. aureus, and mutations in purR result in...
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Nutrient acquisition is a central challenge for all organisms. For the fungal pathogen Candida albicans, utilization of amino acids has been shown to be critical for survival, immune evasion, and escape, while the importance of catabolism of host-derived proteins and peptides in vivo is less well understood. Stp1 and Stp2 are paralogous transcription factors (TFs) regulated by the Ssy1-Ptr3-Ssy5 (SPS) amino acid sensing system and have been proposed to have distinct, if uncertain, roles in protein...
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LuxS/AI-2 is an important quorum sensing system which affects the growth, biofilm formation, virulence, and metabolism of bacteria. LuxS is encoded by the luxS gene, but how this gene is associated with a diverse array of physiological activities in Edwardsiella piscicida (E. piscicida) is not known. Here, we constructed an luxS gene mutant strain, the luxS strain, to identify how LuxS/AI-2 affects pathogenicity. The results showed that LuxS was not found in the luxS gene mutant strain, and this...
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Endothelial activation and microvascular dysfunction are key pathogenic processes in severe malaria. We evaluated the early role of these processes in experimentally induced Plasmodium falciparum and P. vivax infection. Participants were enrolled in induced blood-stage malaria clinical trials. Plasma osteoprotegerin, angiopoietin-2, and von Willebrand Factor (vWF) levels were measured as biomarkers of endothelial activation. Microvascular function was assessed using peripheral arterial tonometry...
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The spirochete Borrelia burgdorferi sensu lato is the causative agent of Lyme disease (LD). The spirochetes produce the CspZ protein that binds to a complement regulator, factor H (FH). Such binding downregulates activation of host complement to facilitate spirochete evasion of complement killing. However, vaccination with CspZ does not protect against LD infection. In this study, we demonstrated that immunization with CspZ-YA, a CspZ mutant protein with no FH-binding activity, protected mice from...
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Glaesserella (Haemophilus) parasuis is a commensal bacterium of the upper respiratory tract in pigs and also the causative agent of Glässer’s disease, which causes significant morbidity and mortality in pigs worldwide. Isolates are characterized into 15 serovars by their capsular polysaccharide, which has shown a correlation with isolate pathogenicity. To investigate the role the capsule plays in G. parasuis virulence and host interaction, a capsule mutant of the serovar 5 strain HS069 was generated...
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Efficient delivery of antigenic cargo to trigger protective immune responses is critical to the success of vaccination. Genetically engineered microorganisms, including virus, bacteria, and protozoa, can be modified to carry and deliver heterologous antigens to the host immune system. The biological vectors can induce a broad range of immune responses and enhance heterologous antigen-specific immunological outcomes. The protozoan genus Eimeria is widespread in domestic animals, causing serious coccidiosis....
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Localized skin lesions are characteristic of cutaneous leishmaniasis (CL); however, Leishmania (Viannia) species, which are responsible for most CL cases in the Americas, can spread systemically, sometimes resulting in mucosal disease. Detection of Leishmania has been documented in healthy mucosal tissues (conjunctiva, tonsils, and nasal mucosa) and healthy skin of CL patients and in individuals with asymptomatic infection in areas of endemicity of L. (V.) panamensis and L. (V.) braziliensis transmission....
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The translocated actin recruiting phosphoprotein (Tarp) is a multidomain type III secreted effector used by Chlamydia trachomatis. In aggregate, existing data suggest a role of this effector in initiating new infections. As new genetic tools began to emerge to study chlamydial genes in vivo, we speculated as to what degree Tarp function contributes to Chlamydia’s ability to parasitize mammalian host cells. To address this question, we generated a complete tarP deletion mutant using the fluorescence-reported...
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Legionella pneumophila, the etiological agent of Legionnaires’ disease, employs an arsenal of hundreds of Dot/Icm-translocated effector proteins to facilitate replication within eukaryotic phagocytes. Several effectors, called metaeffectors, function to regulate the activity of other Dot/Icm-translocated effectors during infection. The metaeffector Lpg2505 is essential for L. pneumophila intracellular replication only when its cognate effector, SidI, is present. SidI is a cytotoxic effector that...
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Implanted medical device-associated infections pose significant health risks, as they are often the result of bacterial biofilm formation. Staphylococcus aureus is a leading cause of biofilm-associated infections which persist due to mechanisms of device surface adhesion, biofilm accumulation, and reprogramming of host innate immune responses. We found that the S. aureus fibronectin binding protein A (FnBPA) is required for normal biofilm development in mammalian serum and that the SaeRS two-component...
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A 62-year-old man presented to our institute with diarrhoea and dysuria on a background of subtotal colectomy and end ileostomy and biological therapy for Crohn’s disease. He was diagnosed with urinary tract infection and acute kidney injury (AKI). Renal ultrasound suggested left hydronephrosis, with renal protocol computed tomography (CT) showing a large pelvic mass. Magnetic resonance imaging (MRI) of the pelvis demonstrated a rectal tumour invading the bladder and compressing both ureters. He...
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Adenocarcinoma of the bowel is a dreadful sequelae of inflammatory bowel disease that can be difficult to diagnose and has been shown to have poor prognosis. The diagnosis is often made on histopathological examination of the resected specimen for what is suspected to be an exacerbation of the underlying intestinal Crohn’s. A 39-year-old woman who was being treated for small bowel Crohn’s disease for 4 years presented with features of intermittent intestinal obstruction that was refractory to medical...
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A middle-aged woman was hospitalised for generalised, painful skin lesions 6 weeks after a successful double-lung transplant. She had end-stage lung disease associated with chronic obstructive pulmonary disease due to alpha-1 antitrypsin deficiency, and she had been treated with itraconazole for 16 months because of lung infection associated with Malbranchea spp. Results of a skin biopsy of the initial lesion on her arm showed non-specific dermal inflammation, presumably due to reactivation of the...
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A 45-year-old woman with a medical history of ulcerative colitis (UC) presented with difficulty in breathing. The patient was diagnosed with UC a month prior to presentation and was started on mesalamine suppository. Chest x-ray (CXR) on presentation showed bilateral pleural effusion, which was confirmed on CT angiogram of the chest. Diagnostic and therapeutic thoracentesis was performed and 0.7 L of pleural fluid was removed from the left side. The pleural fluid analysis was consistent with exudative...
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A 20-year-old man presented to us with injury to the left eye by a glass bulb 3 weeks ago. The acute injury resolved with a peculiar residual localised corneal oedema in the inferior one-third of the cornea . This localised oedema in absence of any evidence of a localised visible injury to the cornea indicated towards a possible retained foreign body. The foreign body visibility was equivocal on gonioscopy. Subsequently via a limbal incision, an endoscope was introduced into the anterior chamber....
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Antimicrobial peptides play an important role in host defense against Vibrio cholerae. Generally, the V. cholerae O1 classical biotype is polymyxin B (PB) sensitive and El Tor is relatively resistant. Detection of classical biotype traits like the production of classical cholera toxin and PB sensitivity in El Tor strains has been reported in recent years, including in the devastating Yemen cholera outbreak during 2016-2018. To investigate the factor(s) responsible for the shift in the trend of sensitivity...
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The intracellular lifestyle of bacteria is widely acknowledged to be an important mechanism in chronic and recurring infection. Among the Staphylococcus genus, only Staphylococcus aureus and Staphylococcus pseudintermedius have been clearly identified as intracellular in nonprofessional phagocytic cells (NPPCs), for which the mechanism is mainly fibronectin-binding dependent. Here, we used bioinformatics tools to search for possible new fibronectin-binding proteins (FnBP-like) in other Staphylococcus...
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A Yersinia pestis mutant synthesizing an adjuvant form of lipid A (monophosphoryl lipid A, MPLA) displayed increased biogenesis of bacterial outer membrane vesicles (OMVs). To enhance the immunogenicity of the OMVs, we constructed an Asd-based balanced-lethal host-vector system that oversynthesized the LcrV antigen of Y. pestis, raised the amounts of LcrV enclosed in OMVs by the type II secretion system, and eliminated harmful factors like plasminogen activator (Pla) and murine toxin from the OMVs....
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Mycoplasma gallisepticum is the primary etiological agent of chronic respiratory disease in chickens. Live attenuated vaccines are most commonly used in the field to control the disease, but current vaccines have some limitations. Vaxsafe MG (strain ts-304) is a new vaccine candidate that is efficacious at a lower dose than the current commercial vaccine strain ts-11, from which it is derived. In this study, the transcriptional profiles of the trachea of unvaccinated chickens and chickens vaccinated...
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Brucella spp. are facultative intracellular bacteria notorious for their ability to induce a chronic, and often lifelong, infection known as brucellosis. To date, no licensed vaccine exists for prevention of human disease, and mechanisms underlying chronic illness and immune evasion remain elusive. We and others have observed that B cell-deficient mice challenged with Brucella display reduced bacterial burden following infection, but the underlying mechanism has not been clearly defined. Here, we...
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Gamma interferon (IFN-)-induced innate immune responses play important roles in the inhibition of Toxoplasma gondii infection. It has been reported that IFN- stimulates non-acidification-dependent growth restriction of T. gondii in HeLa cells, but the mechanism remains unclear. Here, we found that -aminobutyric acid (GABA) receptor-associated protein-like 2 (GABARAPL2) plays a critical role in parasite restriction in IFN--treated HeLa cells. GABARAPL2 is recruited to membrane structures surrounding...
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Phagocytosis is the key mechanism for host control of Pseudomonas aeruginosa, a motile Gram-negative, opportunistic bacterial pathogen which frequently undergoes adaptation and selection for traits that are advantageous for survival. One such clinically relevant adaptation is the loss of bacterial motility, observed within chronic infections, that is associated with increased antibiotic tolerance and phagocytic resistance. Previous studies using phagocytes from a leukocyte adhesion deficiency type...
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Programmed death-ligand 1 (PD-L1/B7-H1) serves as a cosignaling molecule in cell-mediated immune responses and contributes to chronicity of inflammation and the escape of tumor cells from immunosurveillance. Here, we investigated the molecular mechanisms leading to PD-L1 upregulation in human oral carcinoma cells and in primary human gingival keratinocytes in response to infection with Porphyromonas gingivalis (P. gingivalis), a keystone pathogen for the development of periodontitis. The bacterial...
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Bovine digital dermatitis (BDD), an infectious disease of the bovine foot with a predominant treponemal etiology, is a leading cause of lameness in dairy and beef herds worldwide. BDD is poorly responsive to antimicrobial therapy and exhibits a relapsing clinical course; an effective vaccine is therefore urgently sought. Using a reverse vaccinology approach, the present study surveyed the genomes of the three BDD-associated Treponema phylogroups for putative β-barrel outer membrane proteins and considered...
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Zusammenfassung Hintergrund Registerdaten zeigen, dass eine Drainageneinlage im Rahmen bariatrischer Operationen immer noch gängige Praxis in vielen chirurgischen Abteilungen ist. Retrospektive Studien und eine Übersichtsarbeit konnten zeigen, dass die routinemäßige Einlage einer Drainage im Rahmen bariatrischer Operationen nutzlos und potenziell auch gefährdend ist. In der Literatur konnte aufgrund fehlender randomisierter kontrollierter...
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Zusammenfassung Hintergrund Die geringe Anzahl operativ zu versorgender Körperhöhlenverletzungen erfordert ein Umdenken in der chirurgischen Aus- und Weiterbildung. Ein entsprechendes Kursformat wird seit 2014 über die DGAV angeboten. Um Berechtigung, Bedarf, Nutzen und Erfolg eines solchen Kursformates zu erheben, erfolgte eine Evaluation durch die bisherigen Kursteilnehmer. ...
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The COVID-19 pandemic has accounted for tens of thousands of deaths and ultimately will affect millions more people who will survive. There will be time to mourn the victims and care for the survivors. But it is also time to recognize and thank some of the heroes who have emerged so far.
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