Diet and Microbes in the Pathogenesis of Lupus

Systemic lupus erythematosus (SLE) is a complex autoimmune disorder with no known cure. It is characterized by severe and persistent inflammation that damages multiple organs. To date, treatment and prevention of disease flares have relied on long-term use of anti-inflammatory drugs where side effects are of particular concern. There is a need for better understanding of the disease and for better approaches in SLE treatment and management. In this chapter, we delineate the roles of diet and microbes in the pathogenesis of SLE

Frequency and Anatomical Distribution of Pulmonary Embolism on CT Pulmonary Angiography

Background: Pulmonary embolism, with its growing prevalence, has become a potentially life-threatening medical condition with crucial symptoms. However, prognosis is good if timely diagnosis is made and to the level of segmental and sub segmental arteries as well. Standard computed tomography pulmonary angiography (CTPA) is thus used to diagnose acute pulmonary embolism. Objective: The primary objective of the current study was to determine and investigate the anatomical distribution frequency of pulmonary emboli, where segmental, sub segmental, and lobar arteries on CT pulmonary angiography are included. Methodology: In a descriptive cross-sectional study, single-centered studies and CTPA scans of 98 patients were included. Data was obtained from Shalimar Hospital and University of Lahore – Teaching Hospital, Lahore, Pakistan. Sample size included patients of all age groups with suspected pulmonary embolism, with no differentiation of male or female samples. Results: According to statistics and analysis, the current study results indicated the presence of pulmonary embolism in 36 patients and its absence in 62 patients. Results indicated that amongst the 98 patients scanned, the highest frequency of pulmonary emboli was found in the pulmonary trunk and lobar artery in 8 patients (8.2%). Furthermore, CTPA of the participants detected pulmonary emboli in segmental and sub-segmental arteries of 5 patients (5.1%), with another 2 patients showing pulmonary emboli in only the sub-segmental artery (2.0%). Another 2-2 patients showed pulmonary emboli in lobar and segmental artery and lobar, segmental and sub-segmental artery respectively (2.0%, 2.0%). Conclusion: The largest number of pulmonary emboli were found in the pulmonary trunk, followed by emboli of segmental and lobar arteries in patients. It is concluded that CTPA evaluates pulmonary embolism with great precision and anatomical distribution localized main trunk, and pulmonary artery emboli along with lobar, segmental and sub-segmental artery emboli. Keywords: Computed Tomography Pulmonary Angiography (CTPA), pulmonary emboli, segmental artery, sub segmental artery, lobar arteries DOI: 10.7176/JHMN/100-02 Publication date:May 31st 202

Novel VPS13B Mutations in Three Large Pakistani Cohen Syndrome Families Suggests a Baloch Variant with Autistic-Like Features.

BackgroundCohen Syndrome (COH1) is a rare autosomal recessive disorder, principally identified by ocular, neural and muscular deficits. We identified three large consanguineous Pakistani families with intellectual disability and in some cases with autistic traits.MethodsClinical assessments were performed in order to allow comparison of clinical features with other VPS13B mutations. Homozygosity mapping followed by whole exome sequencing and Sanger sequencing strategies were used to identify disease-related mutations.ResultsWe identified two novel homozygous deletion mutations in VPS13B, firstly a 1 bp deletion, NM_017890.4:c.6879delT; p.Phe2293Leufs*24, and secondly a deletion of exons 37-40, which co-segregate with affected status. In addition to COH1-related traits, autistic features were reported in a number of family members, contrasting with the "friendly" demeanour often associated with COH1. The c.6879delT mutation is present in two families from different regions of the country, but both from the Baloch sub-ethnic group, and with a shared haplotype, indicating a founder effect among the Baloch population.ConclusionWe suspect that the c.6879delT mutation may be a common cause of COH1 and similar phenotypes among the Baloch population. Additionally, most of the individuals with the c.6879delT mutation in these two families also present with autistic like traits, and suggests that this variant may lead to a distinct autistic-like COH1 subgroup

Lactobacillus spp. act in synergy to attenuate splenomegaly and lymphadenopathy in lupus-prone MRL/lpr mice

Commensal bacteria and the immune system have a close and strong relationship that maintains a balance to control inflammation. Alterations of the microbiota, known as dysbiosis, can direct reactivity to self-antigens not only in the intestinal mucosa but also at the systemic level. Our laboratory previously reported gut dysbiosis, particularly lower abundance of bacteria in the family Lactobacillaceae, in lupus-prone MRL/lpr mice, a model of systemic autoimmunity. Restoring the microbiota with a mix of 5 different Lactobacillus species (spp.), L. reuteri, L. oris, L. johnsonii, L. gasseri and L. rhamnosus, attenuated lupus-liked clinical signs, including splenomegaly and lymphadenopathy. However, our understanding of the mechanism was limited. In this study, we first investigated the effects of individual species. Surprisingly, none of the species individually recapitulated the benefits of the mix. Instead, Lactobacillus spp. acted synergistically to attenuate splenomegaly and renal lymphadenopathy through secreted factors and a CX3CR1-dependent mechanism. Interestingly, oral administration of MRS broth exerted the same benefits likely through increasing the relative abundance of endogenous Lactobacillus spp. Mechanistically, we found increased percentages of FOXP3-negative type 1 regulatory T cells with administration of the mix in both spleen and mesenteric lymph nodes. In addition, oral gavage of Lactobacillus spp. decreased the percentage of central memory T cells while increasing that of effector memory T cells in the lymphoid organs. Furthermore, a decreased percentage of double negative T cells was observed in the spleen with the mix. These results suggest that Lactobacillus spp. might act on T cells to attenuate splenomegaly and lymphadenopathy. Together, this study advances our understanding of how Lactobacillus spp. attenuate lupus in MRL/lpr mice. The synergistic action of these bacteria suggests that multiple probiotic bacteria in combination may dampen systemic autoimmunity and benefit lupus patients

Deafness mutation mining using regular expression based pattern matching

<p>Abstract</p> <p>Background</p> <p>While keyword based queries of databases such as Pubmed are frequently of great utility, the ability to use regular expressions in place of a keyword can often improve the results output by such databases. Regular expressions can allow for the identification of element types that cannot be readily specified by a single keyword and can allow for different words with similar character sequences to be distinguished.</p> <p>Results</p> <p>A Perl based utility was developed to allow the use of regular expressions in Pubmed searches, thereby improving the accuracy of the searches.</p> <p>Conclusion</p> <p>This utility was then utilized to create a comprehensive listing of all DFN deafness mutations discussed in Pubmed records containing the keywords "human ear".</p

Global, regional, and national burden of meningitis and its aetiologies, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Background: Although meningitis is largely preventable, it still causes hundreds of thousands of deaths globally each year. WHO set ambitious goals to reduce meningitis cases by 2030, and assessing trends in the global meningitis burden can help track progress and identify gaps in achieving these goals. Using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, we aimed to assess incident cases and deaths due to acute infectious meningitis by aetiology and age from 1990 to 2019, for 204 countries and territories. Methods: We modelled meningitis mortality using vital registration, verbal autopsy, sample-based vital registration, and mortality surveillance data. Meningitis morbidity was modelled with a Bayesian compartmental model, using data from the published literature identified by a systematic review, as well as surveillance data, inpatient hospital admissions, health insurance claims, and cause-specific meningitis mortality estimates. For aetiology estimation, data from multiple causes of death, vital registration, hospital discharge, microbial laboratory, and literature studies were analysed by use of a network analysis model to estimate the proportion of meningitis deaths and cases attributable to the following aetiologies: Neisseria meningitidis, Streptococcus pneumoniae, Haemophilus influenzae, group B Streptococcus, Escherichia coli, Klebsiella pneumoniae, Listeria monocytogenes, Staphylococcus aureus, viruses, and a residual other pathogen category. Findings: In 2019, there were an estimated 236 000 deaths (95% uncertainty interval [UI] 204 000–277 000) and 2·51 million (2·11–2·99) incident cases due to meningitis globally. The burden was greatest in children younger than 5 years, with 112 000 deaths (87 400–145 000) and 1·28 million incident cases (0·947–1·71) in 2019. Age-standardised mortality rates decreased from 7·5 (6·6–8·4) per 100 000 population in 1990 to 3·3 (2·8–3·9) per 100 000 population in 2019. The highest proportion of total all-age meningitis deaths in 2019 was attributable to S pneumoniae (18·1% [17·1–19·2]), followed by N meningitidis (13·6% [12·7–14·4]) and K pneumoniae (12·2% [10·2–14·3]). Between 1990 and 2019, H influenzae showed the largest reduction in the number of deaths among children younger than 5 years (76·5% [69·5–81·8]), followed by N meningitidis (72·3% [64·4–78·5]) and viruses (58·2% [47·1–67·3]). Interpretation: Substantial progress has been made in reducing meningitis mortality over the past three decades. However, more meningitis-related deaths might be prevented by quickly scaling up immunisation and expanding access to health services. Further reduction in the global meningitis burden should be possible through low-cost multivalent vaccines, increased access to accurate and rapid diagnostic assays, enhanced surveillance, and early treatment. Funding: Bill & Melinda Gates Foundation

The impact of different biochars on Stemphylium leaf blight SLB suppression and productivity of onion Allium cepa L.

Objectives: Onion is a highly consumed vegetable crop in many countries, being a vital component of every dish. Recent studies indicated that different plant residues’ and animal manure-based biochars have strong impacts on the growth and development of plants. However, the impact of these biochars on disease suppression remains elusive. Therefore, this two-year study assessed the impact of animal and plant residues-based biochars on the suppression of Stemphylium leaf blight (SLB) of onion and productivity of the crop. Methods: Three pyrolyzed biochars cotton sticks, wheat straw and poultry litter) were used in the study. Biochars were prepared in the laboratory and applied to soil prior to crop sowing in same concentration during both years of study. Results: Poultry litter biochar had the highest impact on allometric traits and productivity of onion, and successfully reduced SLB severity. The control treatment had the lowest productivity and the highest disease severity during both years of the study. The remaining biochars (cotton sticks and wheat straw) hadmoderate influence on growth and development of onion plants. The disease severity was higher compared to poultry litter; however, it was lower in both biochars than control treatment. It is concluded that different animal and plant residues-based biochars could be used to improve plant health. Nonetheless, the response of these biochars will be crop-specific. Conclusion: Poultry litter biochar can be successfully used to suppress SLB in onion and productivity of the crop. Nevertheless, the actual mechanisms involved in disease suppression warrant further investigation

Global mortality associated with 33 bacterial pathogens in 2019: a systematic analysis for the Global Burden of Disease Study 2019

Background: Reducing the burden of death due to infection is an urgent global public health priority. Previous studies have estimated the number of deaths associated with drug-resistant infections and sepsis and found that infections remain a leading cause of death globally. Understanding the global burden of common bacterial pathogens (both susceptible and resistant to antimicrobials) is essential to identify the greatest threats to public health. To our knowledge, this is the first study to present global comprehensive estimates of deaths associated with 33 bacterial pathogens across 11 major infectious syndromes. Methods: We estimated deaths associated with 33 bacterial genera or species across 11 infectious syndromes in 2019 using methods from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, in addition to a subset of the input data described in the Global Burden of Antimicrobial Resistance 2019 study. This study included 343 million individual records or isolates covering 11 361 study-location-years. We used three modelling steps to estimate the number of deaths associated with each pathogen: deaths in which infection had a role, the fraction of deaths due to infection that are attributable to a given infectious syndrome, and the fraction of deaths due to an infectious syndrome that are attributable to a given pathogen. Estimates were produced for all ages and for males and females across 204 countries and territories in 2019. 95% uncertainty intervals (UIs) were calculated for final estimates of deaths and infections associated with the 33 bacterial pathogens following standard GBD methods by taking the 2·5th and 97·5th percentiles across 1000 posterior draws for each quantity of interest. Findings: From an estimated 13·7 million (95% UI 10·9–17·1) infection-related deaths in 2019, there were 7·7 million deaths (5·7–10·2) associated with the 33 bacterial pathogens (both resistant and susceptible to antimicrobials) across the 11 infectious syndromes estimated in this study. We estimated deaths associated with the 33 bacterial pathogens to comprise 13·6% (10·2–18·1) of all global deaths and 56·2% (52·1–60·1) of all sepsis-related deaths in 2019. Five leading pathogens—Staphylococcus aureus, Escherichia coli, Streptococcus pneumoniae, Klebsiella pneumoniae, and Pseudomonas aeruginosa—were responsible for 54·9% (52·9–56·9) of deaths among the investigated bacteria. The deadliest infectious syndromes and pathogens varied by location and age. The age-standardised mortality rate associated with these bacterial pathogens was highest in the sub-Saharan Africa super-region, with 230 deaths (185–285) per 100 000 population, and lowest in the high-income super-region, with 52·2 deaths (37·4–71·5) per 100 000 population. S aureus was the leading bacterial cause of death in 135 countries and was also associated with the most deaths in individuals older than 15 years, globally. Among children younger than 5 years, S pneumoniae was the pathogen associated with the most deaths. In 2019, more than 6 million deaths occurred as a result of three bacterial infectious syndromes, with lower respiratory infections and bloodstream infections each causing more than 2 million deaths and peritoneal and intra-abdominal infections causing more than 1 million deaths. Interpretation: The 33 bacterial pathogens that we investigated in this study are a substantial source of health loss globally, with considerable variation in their distribution across infectious syndromes and locations. Compared with GBD Level 3 underlying causes of death, deaths associated with these bacteria would rank as the second leading cause of death globally in 2019; hence, they should be considered an urgent priority for intervention within the global health community. Strategies to address the burden of bacterial infections include infection prevention, optimised use of antibiotics, improved capacity for microbiological analysis, vaccine development, and improved and more pervasive use of available vaccines. These estimates can be used to help set priorities for vaccine need, demand, and development. Funding: Bill & Melinda Gates Foundation, Wellcome Trust, and Department of Health and Social Care, using UK aid funding managed by the Fleming Fund