Salmonella Typhi, Paratyphi A, Enteritidis and Typhimurium core proteomes reveal differentially expressed proteins linked to the cell surface and pathogenicity

Background: Salmonella enterica subsp. enterica contains more than 2,600 serovars of which four are of major medical relevance for humans. While the typhoidal serovars (Typhi and Paratyphi A) are human-restricted and cause enteric fever, non-typhoidal Salmonella serovars (Typhimurium and Enteritidis) have a broad host range and predominantly cause gastroenteritis. Methodology/Principle findings: We compared the core proteomes of Salmonella Typhi, Paratyphi A, Typhimurium and Enteritidis using contemporary proteomics. For each serovar, five clinical isolates (covering different geographical origins) and one reference strain were grown in vitro to the exponential phase. Levels of orthologous proteins quantified in all four serovars and within the typhoidal and non-typhoidal groups were compared and subjected to gene ontology term enrichment and inferred regulatory interactions. Differential expression of the core proteomes of the typhoidal serovars appears mainly related to cell surface components and, for the non-typhoidal serovars, to pathogenicity. Conclusions/Significance: Our comparative proteome analysis indicated differences in the expression of surface proteins between Salmonella Typhi and Paratyphi A, and in pathogenesis-related proteins between Salmonella Typhimurium and Enteritidis. Our findings may guide future development of novel diagnostics and vaccines, as well as understanding of disease progression. Author summary: With an estimated 20 million typhoid cases and an even higher number of non-typhoid cases the health burden caused by salmonellosis is huge. Salmonellosis is caused by the bacterial species Salmonella enterica and over 2500 different serovars exist, of which four are of major medical relevance for humans: Typhi and Paratyphi A cause typhoid fever while Typhimurium and Enteritidis are the dominant cause of non-typhoidal Salmonella infections. The proteome is the entire set of proteins that is expressed by a genome and the core proteome are all orthologous proteins detected in a given sample set. In this study we have investigated differential expression of the core proteomes of the Salmonella serovars Typhi, Paratyphi A, Typhimurium and Enteritidis, as well as the regulating molecules. Our comparative proteome analysis indicated differences in the expression of surface proteins between the serovars Typhi and Paratyphi A, and in pathogenesis-related proteins between Typhimurium and Enteritidis. Our findings in proteome-wide expression may guide the development of novel diagnostics and vaccines for Salmonella, as well as understanding of disease

Impact of Obstructive Sleep Apnea (OSA) in COVID-19 Survivors, Symptoms Changes Between 4-Months and 1 Year After the COVID-19 Infection

Objective: To determine the association between Obstructive Sleep Apnea (OSA) with long-term symptoms and inflammatory cytokines, exploring the changes between 4-months and 1-year after COVID-19 infection. Methods: We conducted an observational, prospective cohort study, including patients ≥18 years old with confirmed diagnosis of COVID-19 between April to July 2020. All participants underwent two clinical follow-up visits, the first at 4-months (Visit 1) and the second at 1 year, after SARS-CoV-2 infection (Visit 2). Plasma glucose, total cholesterol, HDL, and triglycerides. Regarding pulmonary function, spirometry and lung diffusion capacity tests were assessed. For mental and neurocognitive evaluation, a short-form (SF-12), Beck depression and Hospital-Anxiety depression questionnaires were conducted at both time-points, whereas the Montreal Cognitive assessment was conducted during the second follow-up. Regarding to sleep evaluation, Epworth Sleepiness Scale, Insomnia Severity index and STOP-BANG questionnaire were conducted. Additionally, a home sleep apnea test and 7-day wrist actigraphy were performed in all participants. Inflammatory cytokines were measured using an inflammatory cytokine bead array kit. p-values < 0.05 were considered statistically significant and statistical analyses were performed using R software. Results: A total of 60 patients were included in the first follow-up, from which 57 completed the second follow-up. The mean age was 46.4 years-old (SD ± 13.1) and 53.3% were male. 30% of cases reported mild COVID-19 infection, 28.3% with moderate illness, and 41.6% with severe illness. Moreover, 56.6% of them were admitted to the ICU. Regarding to metabolic values, the OSA group showed higher values of insulin resistance (IR) (27%), systolic blood pressure (SBP) 135.2 (±19.1), dyslipidemia (67.5%), total cholesterol 202.1 (±60.5), triglycerides 176.1 (±119.0) and HOMA-IR 9.0 (±18.8) in comparison with the non-OSA group. 1 year after COVID-19 infection, DLCO test remains abnormal in OSA patients (25% OSA vs. 3.6% non-OSA, p = 0.02). Finally, those participants with OSA who develop ARDS reported an adjusted OR 20.4 (95%-CI, 1.04-504) risk of neurocognitive impairment. Discussion: Among patients with previous COVID-19, OSA impact the development of incident glycemic, neurocognitive impairment, and abnormal functional pulmonary changes that persist up to 1 year since acute phase.This study was supported by the Agencia Nacional de Investigación y Desarrollo (ANID, COVID1005), Chilean Government. GL declares funding for research by the American Academy of Sleep Medicine (AASM, 254-FP-21). JG, FB, and AT declare funded by ISCIII (CIBERESUCICOVID, COV20/00110). EN-L, SS, CC, RQ and BA were funded by Fondecyt 1211480 and COVID-19 Genomics Network (C19-GenoNet) ACT210085. Figure 1 was created with BioRender.com and Flow Cytometer was funded by EQM150061 (FONDEQUIP-ANID)

An African Salmonella Typhimurium ST313 sublineage with extensive drug-resistance and signatures of host adaptation

Abstract: Bloodstream infections by Salmonella enterica serovar Typhimurium constitute a major health burden in sub-Saharan Africa (SSA). These invasive non-typhoidal (iNTS) infections are dominated by isolates of the antibiotic resistance-associated sequence type (ST) 313. Here, we report emergence of ST313 sublineage II.1 in the Democratic Republic of the Congo. Sublineage II.1 exhibits extensive drug resistance, involving a combination of multidrug resistance, extended spectrum β-lactamase production and azithromycin resistance. ST313 lineage II.1 isolates harbour an IncHI2 plasmid we name pSTm-ST313-II.1, with one isolate also exhibiting decreased ciprofloxacin susceptibility. Whole genome sequencing reveals that ST313 II.1 isolates have accumulated genetic signatures potentially associated with altered pathogenicity and host adaptation, related to changes observed in biofilm formation and metabolic capacity. Sublineage II.1 emerged at the beginning of the 21st century and is involved in on-going outbreaks. Our data provide evidence of further evolution within the ST313 clade associated with iNTS in SSA

Modeling of information recording and selective etching processes in inorganic resists

Theoretical consideration and computer modeling of information pit recording and etching processes in chalcogenide vitreous semiconductors are proposed, namely we demonstrate how to record and develop information pits with the necessary shape and sizes in the inorganic resist using focused Gaussian laser beam and selective etching. It has been shown that phototransformed region cross-section could be almost trapezoidal or parabolic depending on the resist material optical absorption, recording beam power, exposure, etchant selectivity and etching time. Namely, during the laser illumination and thermal heating caused by it, photosensitive material is the quasi-equilibrium microscopic mixture of the transformed and nontransformed phases with different optical absorption coefficients: temperature dependent near the absorption edge «transformed» coefficient бe and almost independent coefficient α0 . If αe ≤ α0 e after thermal heating, the photo-transformed region «bleaches» and the pit depth increases more rapidly under the following laser power increasing. If αe > α0 , the phototransformed region «darkens» and the pit depth increases sub-linearly or even saturates under the following laser power increasing. Thus, almost parabolic or flattened pits appear when αe ≥ α0, whereas the pits with elongated tops appear when αe << α0. After illumination, the spatial distribution of photo-transformed material fraction was calculated using the Kolmogorov-Awrami equation. Analyzing obtained results, we derived a rather simple approximate analytical expression for the dependence of the phototransformed region width and depth on the recording Gaussian beam power, radius and exposure time. Then the selective etching process was simulated numerically. The obtained results quantitatively describe the characteristics of pits recorded by the Gaussian laser beam in thin layers of As₄₀S₆₀ chalcogenide semiconductor. Our model open possibilities how to select the necessary recording procedure and etching conditions in order to obtain pits with the optimum shape and sizes.Запропоновано теоретичний розгляд та комп’ютерне моделювання процесів запису інформації та селективного травлення в халькогенідних напівпровідниках. Змодульовано процес одержання інформаційних питів необхідної форми та розміру у неорганічному резисті, використовуючи сфокусований гаусівський лазерний пучок та селективне травлення. Показано, що переріз фототрансформованої області змінюється від майже трапецієвидного до параболічного в залежності від коефіцієнта оптичного поглинання, потужності лазерного пучка, експозиції, селективності травника та часу травлення. Просторовий розподіл долі фототрансформованого матеріалу розраховано з рівняння Колмогорова-Аврами. Проаналізовано одержані результати й виведено досить простий наближений аналітичний вираз для залежності ширини та висоти фототрансформованої області від потужності лазерного пучка, його радіусу, часу експонування та селективності травника. Одержані результати добре описують характеристики пітів, записаних у тонких шарах халькогеніду As₄₀S₆₀. Модель відкриває реальну можливість добору умов запису та травлення резисту, необхідних для одержання пітів з оптимальними розмірами.Предложено теоретическое рассмотрение и компьютерное моделирование процессов записи информации и селективного травления в халькогенидных полупроводниках. Смоделирован процесс получения информационных питов необходимой формы и размеров в неорганическом резисте, используя сфокусированный гауссовский лазерный пучок и селективное травление. Показано, что сечение фототрансформированной области может изменяться от практически трапециевидного до параболического в зависимости от коэффициента оптического поглощения, мощности лазерного пучка, экспозиции, селективности травителя и времени травления. Пространственное распределение доли фототрансформированного материала рассчитано из уравнения Колмогорова-Аврами. Проанализированы полученные результаты и выведено достаточно простое приближенное аналитическое выражение для зависимости ширины и высоты фототрансформированной области от мощности лазерного пучка, его радиуса, времени экспонирования и селективности травителя. Полученные результаты хорошо описывают характеристики питов, записанных в тонких слоях халькогенида As₄₀S₆₀. Модель открывает реальную возможность выбора условий записи и травления резиста, необходимых для получения питов с оптимальными размерами

Experiences and Lessons from a Multicountry NIDIAG Study on Persistent Digestive Disorders in the Tropics.

<p>Experiences and Lessons from a Multicountry NIDIAG Study on Persistent Digestive Disorders in the Tropics</p

Mild and moderate COVID-19 during Alpha, Delta and Omicron pandemic waves in urban Maputo, Mozambique, December 2020-March 2022: A population-based surveillance study

In sub-Saharan Africa, reported COVID-19 numbers have been lower than anticipated, even when considering populations’ younger age. The extent to which risk factors, established in industrialised countries, impact the risk of infection and of disease in populations in sub-Saharan Africa, remains unclear. We estimated the incidence of mild and moderate COVID-19 in urban Mozambique and analysed factors associated with infection and disease in a population-based surveillance study. During December 2020-March 2022, 1,561 households (6,049 participants, median 21 years, 54.8% female, 7.3% disclosed HIV positive) of Polana Caniço, Maputo, Mozambique, were visited biweekly to report respiratory symptoms, anosmia, or ageusia, and self-administer a nasal swab for SARS-CoV-2 testing. Every three months, dried blood spots of a subset of participants (1,412) were collected for detection of antibodies against SARS-CoV-2 spike glycoprotein and nucleocapsid protein. Per 1000 person-years, 364.5 (95%CI 352.8–376.1) respiratory illness episodes were reported, of which 72.2 (95%CI 60.6–83.9) were COVID-19. SARS-CoV-2 seroprevalence rose from 4.8% (95%CI 1.1–8.6%) in December 2020 to 34.7% (95%CI 20.2–49.3%) in June 2021, when 3.0% were vaccinated. Increasing age, chronic lung disease, hypertension, and overweight increased risk of COVID-19. Older age increased the risk of SARSCoV-2 seroconversion. We observed no association between socio-economic status, behaviour and COVID-19 or SARS-CoV-2 seroconversion. Active surveillance in an urban population confirmed frequent COVID-19 underreporting, yet indicated that the large majority of cases were mild and non-febrile. In contrast to reports from industrialised countries, social deprivation did not increase the risk of infection nor disease

A genomic appraisal of invasive Salmonella Typhimurium and associated antibiotic resistance in sub-Saharan Africa

Invasive non-typhoidal Salmonella (iNTS) disease manifesting as bloodstream infection with high mortality is responsible for a huge public health burden in sub-Saharan Africa. Salmonella enterica serovar Typhimurium (S. Typhimurium) is the main cause of iNTS disease in Africa. By analysing whole genome sequence data from 1303 S. Typhimurium isolates originating from 19 African countries and isolated between 1979 and 2017, here we show a thorough scaled appraisal of the population structure of iNTS disease caused by S. Typhimurium across many of Africa’s most impacted countries. At least six invasive S. Typhimurium clades have already emerged, with ST313 lineage 2 or ST313-L2 driving the current pandemic. ST313-L2 likely emerged in the Democratic Republic of Congo around 1980 and further spread in the mid 1990s. We observed plasmid-borne as well as chromosomally encoded fluoroquinolone resistance underlying emergences of extensive-drug and pan-drug resistance. Our work provides an overview of the evolution of invasive S. Typhimurium disease, and can be exploited to target control measures

A genomic appraisal of invasive Salmonella Typhimurium and associated antibiotic resistance in sub-Saharan Africa

Invasive non-typhoidal Salmonella (iNTS) disease manifesting as bloodstream infection with high mortality is responsible for a huge public health burden in sub-Saharan Africa. Salmonella enterica serovar Typhimurium (S. Typhimurium) is the main cause of iNTS disease in Africa. By analysing whole genome sequence data from 1303 S. Typhimurium isolates originating from 19 African countries and isolated between 1979 and 2017, here we show a thorough scaled appraisal of the population structure of iNTS disease caused by S. Typhimurium across many of Africa’s most impacted countries. At least six invasive S. Typhimurium clades have already emerged, with ST313 lineage 2 or ST313-L2 driving the current pandemic. ST313-L2 likely emerged in the Democratic Republic of Congo around 1980 and further spread in the mid 1990s. We observed plasmid-borne as well as chromosomally encoded fluoroquinolone resistance underlying emergences of extensive-drug and pan-drug resistance. Our work provides an overview of the evolution of invasive S. Typhimurium disease, and can be exploited to target control measures

Assessment of desiccants and their instructions for use in rapid diagnostic tests

BACKGROUND: Malaria rapid diagnostic tests (RDTs) are protected from humidity-caused degradation by a desiccant added to the device packaging. The present study assessed malaria RDT products for the availability, type and design of desiccants and their information supplied in the instructions for use (IFU). METHODS: Criteria were based on recommendations of the World Health Organization (WHO), the European Community (CE) and own observations. Silica gel sachets were defined as selfindicating (all beads coated with a humidity indicator that changes colour upon saturation), partial-indicating (part of beads coated) and non-indicating (none of the beads coated). Indicating silica gel sachets were individually assessed for humidity saturation and (in case of partial-indicating silica gels) for the presence of indicating beads. RESULTS: Fifty malaria RDT products from 25 manufacturers were assessed, 14 (28%) products were listed by the "Global Fund Quality Assurance Policy" and 31 (62%) were CE-marked. All but one product contained a desiccant, mostly (47/50, 94%) silica gel. Twenty (40%) RDT products (one with no desiccant and 19 with non-indicating desiccant) did not meet the WHO guidelines recommending indicating desiccant. All RDT products with self- or partialindicating silica gel (n = 22 and 8 respectively) contained the toxic cobalt dichloride as humidity indicator. Colour change indicating humidity saturation was observed for 8/16 RDT products, at a median incidence of 0.8% (range 0.05%-4.6%) of sachets inspected. In all RDTs with partial-indicating silica gel, sachets with no colour indicating beads were found (median proportion 13.5% (0.6% - 17.8%) per product) and additional light was needed to assess the humidity colour. Less than half (14/30, 47%) IFUs of RDT products with indicating desiccants mentioned to check the humidity saturation before using the test. Information on properties, safety hazards and disposal of the desiccant was not included in any of the IFUs. There were no differences between Global Fund-listed and CE marked RDT products compared to those which were not. Similar findings were noted for a panel of 11 HIV RDTs that was assessed with the same checklist as the malaria RDTs. CONCLUSION: RDTs showed shortcomings in desiccant type and information supplied in the IFU