Socioeconomic indices guided linear mixed-effects and meta-regression modelling of the temporal, global and regional prevalence of Helicobacter pylori in environmental waters: A class I carcinogen.

Environmental waters (EW) substantially lend to the transmission of Helicobacter pylori (Hp). But the increase in Hp infections and antimicrobial resistance is often attributed to socioeconomic status. The connection between socioeconomic status and Hp prevalence in EW is however yet to be investigated. This study aimed to assess the impacts of socioeconomic indices (SI: continent, world bank region (WBR), world bank income (WBI), WHO region, Socio-demographic Index (SDI quintile), Sustainable Development Index (SuDI), and Human Development Index (HDI)) on the prevalence of Hp in EW. Hp-EW data were fitted to a generalized linear mixed-effects model and SI-guided meta-regression models with a 1000-resampling test. The worldwide prevalence of Hp in EW was 21.76% [95% confidence interval [CI]: 10.29-40.29], which declined significantly from 59.52% [43.28-74.37] in 1990-99 to 19.36% [3.99-58.09] in 2010-19 and with increasing trend in 2020-22 (33.33%, 22.66-45.43). Hp prevalence in EW was highest in North America (45.12%, 17.07-76.66), then Europe (22.38%, 5.96-56.74), South America (22.09%, 13.76-33.49), Asia (2.98%, 0.02-85.17), and Africa (2.56%, 0.00-99.99). It was negligibly different among sampling settings, WBI, and WHO regions demonstrating highest prevalence in rural location [42.62%, 3.07-94.56], HIEs [32.82%, 13.19-61.10], and AMR [39.43%, 19.92-63.01], respectively. However, HDI, sample size, and microbiological method robustly predict Hp prevalence in EW justifying 26.08%, 21.15%, and 16.44% of the true difference, respectively. In conclusion, Hp is highly prevalence in EW across regional/socioeconomic strata and thus challenged the uses of socioeconomic status as surrogate for hygienic/sanitary practices in estimating Hp infection prevalence.

Global and regional prevalence of Helicobacter pylori in drinking waters: A sustainable, human development and socio-demographic indices based meta-regression-modelling.

Helicobacter pylori (Hp) transmission dynamics via drinking water (DW) has a far much higher direct and indirect public health disease burden than previously thought. This study aimed to assess the global prevalence of Hp in DW, distributions across regions and socioeconomic indices (continent, world bank income, Human Development Index (HDI), Sustainable Development Index (SuDI), Socio-Demographic Index (SDI) quintile, and WHO regions). Hp-DW related data mined from five databases until 10/12/2022 according to PRISMA standard were quality-appraised and fitted to a generalized linear mixed-effects model. Sub-group analysis and meta-regression-modelling coupled with a 1000-permutation test (⁎) were conducted. The global prevalence of Hp in DW was 15.7% (95% confidence interval [CI]: 7.98-27.5), which varied significantly by sampling methods (Moore swabbing (61.0% [0.00-100.0]) vs. grab sampling (13.68%[6.99-25.04])) and detection technique (non-culture (21.35%[9.13-42.31]) vs. cultured-based methods (Psubgroup < 0.01)). The period 1990-99 had the highest prevalence (41.24% [0.02-99.97]). Regarding regional designations, Hp prevalence in DW was significantly different being highest in North America (61.82% [41.03-79.02]) by continents, AMR (42.66% [20.81-67.82]) by WHO group, high HDI (24.64% [10.98-46.43]) by HDI group and North America (61.90% [2.79-98.93]) by world bank region (Psubgroup < 0.01). Generally, sample preparation, SuDI grouping, and detection/confirmation techniques, have significant effects on the detection/prevalence of Hp in DW (Psubgroup < 0.01). Hp prevalence in DW was not significantly different among rural and urban DW (Psubgroup = 0.90), world bank income groups (Psubgroup = 0.15), and SDI quintiles (Psubgroup = 0.07). Among the predictors examined, only sample size (p < 0.1, R∗2(coefficient of determinant) = 15.29%), continent (p∗val = 0.04), HDI (p∗val = 0.02), HDI group (p∗val = 0.05), and microbiological methods (p < 0.1; R∗2=28.09 %) predicted Hp prevalence in DW robustly. In conclusion, Hp prevalence is still endemic in DW regardless of the regional designations/improve DW supplies.

Assessment of Bacterial Transfer From Patient to Chiropractor During Spinal Manipulation.

OBJECTIVE: This study aimed to measure the amount of bacteria that may be transferred from patient to chiropractor during spinal manipulation and the efficacy of decontaminants commonly used by chiropractic practitioners. METHODS: We chose Kwazulu-Natal, South Africa as the location, which is an area with an increased burden of immunocompromised patients resulting from HIV and tuberculosis. In this region, we obtained samples from 40 chiropractors' hands before and after spinal manipulation. Viable counts of colony-forming units were enumerated to verify the presence of bacteria. A modified Kirby-Bauer technique was used to ascertain the efficacy of the top 5 decontaminants used by chiropractors in this area against the bacteria isolated from their hands. RESULTS: Both normal microflora and potentially pathogenic bacteria were found. These included Staphylococcus spp., Micrococcus spp., Bacillus spp., Pseudomonas spp., Escherichia coli, Streptococcus spp., and Staphylococcus aureus. Higher bacterial counts were found on chiropractors' hands after patient contact for spinal manipulation, which are similar to findings from studies of other healthcare personnel. The 5 commonly used disinfectants tested in a lab setting were not as effective against bacterial samples when compared with an antimicrobial pharmaceutical medication. CONCLUSIONS: The net transfer of bacteria to chiropractors' hands from the patient to the practitioner during spinal manipulation included primary and opportunistic pathogens. The detergents commonly used by chiropractors in this region showed varying efficacies against microbial growth when tested in vitro.

Phenotypic and genotypic characterisation of an unique indigenous hypersaline unicellular cyanobacterium, Euhalothece sp.nov.

A novel halotolerant species of cyanobacterium of the order Chroococcales was isolated from hypersaline estuary in Kwa-Zulu Natal, South Africa. A comprehensive polyphasic approach viz., cell morphology, pigment composition and complete genome sequence analysis was conducted to elucidate the taxonomic position of the isolated strain. The blue-green oval to rod-shaped cells were 14-18 µm in size, and contained a high amount of phycocyanin pigments. The strain was moderate thermotolerant/alkalitolerant halophile with the optimum conditions for growth at 35 °C, pH 8.5 and 120 g/l of NaCl. Based on 16S rRNA gene sequence phylogeny, the strain was related to members of the 'Euhalothece' subcluster (99%). The whole genome sequence was determined, and the annotated genes showed a 90% sequence similarity to the gas-vacuolate, spindle-shaped Dactylococcopsis salina PCC 8305. The size of the genome was determined to be 5,113,178 bp and contained 4332 protein-coding genes and 69 RNA genes with a G + C content of 46.7%. Genes encoding osmoregulation, oxidative stress, heat shock, persister cells, and UV-absorbing secondary metabolites, among others, were identified. Based on the phylogenetic analysis of the 16S rRNA gene sequences, physiological data, pigment compositions and genomic data, the strain is considered to represent a novel species of Euhalothece.

Mechanosensing Controlled Directly by Tyrosine Kinases.

To understand how cells form tissues, we need to understand how the tyrosine kinases are involved in controlling cell mechanics, whether they act directly as parts of mechanosensing machines or indirectly. Cells test the critical parameter of matrix rigidity by locally contracting ("pinching") matrices and measuring forces, and the depletion of contractile units causes transformation. We report here that knocking down the receptor tyrosine kinases (RTKs), AXL, and ROR2, alters rigidity sensing and increases the magnitude or duration of local contraction events, respectively. Phospho-AXL and ROR2 localize to contraction units and bind major contractile components, tropomyosin 2.1 (AXL), myosin IIA (AXL), and filamin A (ROR2). At a molecular level, phosphorylated AXL localizes to active myosin filaments and phosphorylates tropomyosin at a tyrosine critical for adhesion formation. ROR2 binding of ligand is unnecessary, but binding filamin A helps function. Thus, AXL and ROR2 alter rigidity sensing and consequently morphogenic processes by directly controlling local mechanosensory contractions without ligands.

Cyclic stretching of soft substrates induces spreading and growth.

In the body, soft tissues often undergo cycles of stretching and relaxation that may affect cell behaviour without changing matrix rigidity. To determine whether transient forces can substitute for a rigid matrix, we stretched soft pillar arrays. Surprisingly, 1-5% cyclic stretching over a frequency range of 0.01-10 Hz caused spreading and stress fibre formation (optimum 0.1 Hz) that persisted after 4 h of stretching. Similarly, stretching increased cell growth rates on soft pillars comparative to rigid substrates. Of possible factors linked to fibroblast growth, MRTF-A (myocardin-related transcription factor-A) moved to the nucleus in 2 h of cyclic stretching and reversed on cessation; but YAP (Yes-associated protein) moved much later. Knockdown of either MRTF-A or YAP blocked stretch-dependent growth. Thus, we suggest that the repeated pulling from a soft matrix can substitute for a stiff matrix in stimulating spreading, stress fibre formation and growth.

Concerted modulation of paxillin dynamics at focal adhesions by Deleted in Liver Cancer-1 and focal adhesion kinase during early cell spreading.

Deleted in Liver Cancer-1 (DLC1) is a RhoGTPase-activating protein (GAP) and a tumor suppressor often downregulated in cancers. It is localized to the focal adhesions (FAs) and its absence leads to enhanced cell migration, invasion, and metastasis. Although DLC1 interacts with focal adhesion kinase (FAK), talin, and tensin, its role in focal adhesions dynamics remains unclear. We examined the effect of DLC1 in Human Foreskin Fibroblasts and determined its localization, dynamics and impact on paxillin by Fluorescence Recovery After Photobleaching at both nascent and mature focal adhesions. During early cell spreading, DLC1 is preferentially localized at the inner/mature adhesions whereas phosphorylated paxillin occupies the outer/nascent FAs. In addition, DLC1 downregulates paxillin turnover in a process, that does not require its GAP activity. Instead, it requires the presence of FAK. Acting in concert, both DLC1 and FAK could provide a unique spatio-temporal mechanism to regulate paxillin function in tissue homeostasis.

Kinetic modelling and characterization of microbial community present in a full-scale UASB reactor treating brewery effluent.

The performance of a full-scale upflow anaerobic sludge blanket (UASB) reactor treating brewery wastewater was investigated by microbial analysis and kinetic modelling. The microbial community present in the granular sludge was detected using fluorescent in situ hybridization (FISH) and further confirmed using polymerase chain reaction. A group of 16S rRNA based fluorescent probes and primers targeting Archaea and Eubacteria were selected for microbial analysis. FISH results indicated the presence and dominance of a significant amount of Eubacteria and diverse group of methanogenic Archaea belonging to the order Methanococcales, Methanobacteriales, and Methanomicrobiales within in the UASB reactor. The influent brewery wastewater had a relatively high amount of volatile fatty acids chemical oxygen demand (COD), 2005 mg/l and the final COD concentration of the reactor was 457 mg/l. The biogas analysis showed 60-69% of methane, confirming the presence and activities of methanogens within the reactor. Biokinetics of the degradable organic substrate present in the brewery wastewater was further explored using Stover and Kincannon kinetic model, with the aim of predicting the final effluent quality. The maximum utilization rate constant U max and the saturation constant (K(B)) in the model were estimated as 18.51 and 13.64 g/l/day, respectively. The model showed an excellent fit between the predicted and the observed effluent COD concentrations. Applicability of this model to predict the effluent quality of the UASB reactor treating brewery wastewater was evident from the regression analysis (R(2) = 0.957) which could be used for optimizing the reactor performance.

Dynamics of passive and active particles in the cell nucleus.

Inspite of being embedded in a dense meshwork of nuclear chromatin, gene loci and large nuclear components are highly dynamic at 37°C. To understand this apparent unfettered movement in an overdense environment, we study the dynamics of a passive micron size bead in live cell nuclei at two different temperatures (25 and 37°C) with and without external force. In the absence of a force, the beads are caged over large time scales. On application of a threshold uniaxial force (about 10(2) pN), the passive beads appear to hop between cages; this large scale movement is absent upon ATP-depletion, inhibition of chromatin remodeling enzymes and RNAi of lamin B1 proteins. Our results suggest that the nucleus behaves like an active solid with a finite yield stress when probed at a micron scale. Spatial analysis of histone fluorescence anisotropy (a measure of local chromatin compaction, defined as the volume fraction of tightly bound chromatin) shows that the bead movement correlates with regions of low chromatin compaction. This suggests that the physical mechanism of the observed yielding is the active opening of free-volume in the nuclear solid via chromatin remodeling. Enriched transcription sites at 25°C also show caging in the absence of the applied force and directed movement beyond a yield stress, in striking contrast with the large scale movement of transcription loci at 37°C in the absence of a force. This suggests that at physiological temperatures, the loci behave as active particles which remodel the nuclear mesh and reduce the local yield stress.

Primary haemophagocytic syndrome in a young girl.

Haemophagocytic syndrome is a life-threatening systemic illness characterized by an uncontrolled inflammatory response. Patients present with fever, hepatosplenomegaly, jaundice and liver dysfunction, neurological manifestations and often pancytopenla. Bone marrow, lymph node, hepatic or splenic biopsy shows macrophages with Ingested blood cells or their precursors. Laboratory markers include elevated triglycerides and ferritin, low fibrinogen with normal or low erythrocyte sedimentation rate (ESR). Familial haemophagocytic lymphohistiocytosis (HLH) is an autosomal recessive disorder. Secondary haemophagocytic syndrome results from infections, malignancy and collagen vascular disorders. We describe a young girl with primary haemophagocytic syndrome.

Probing structural stability of chromatin assembly sorted from living cells.

Post-translational modifications of the histone tails and other chromatin binding proteins affect the stability of chromatin structure. In this study, we have purified chromatin from live cell nuclei using a fluorescence activated cell sorter (FACS) and studied the structural stability of this self-assembled structure. Using total internal reflection fluorescence (TIRF) microscopy, we map the effect of covalent modifications on the interaction of histone-DNA complex, by measuring the dissociation rates of histones from the chromatin fiber in the presence of different salt concentrations. Dynamic force spectroscopy (DFS) experiments were carried out to measure the structural disintegration of large chromatin globules under force. The characteristic rupture of multiple linkages in the large chromatin globules show differences in the stiffness of the higher order structure of chromatin with altered epigenetic states. Our studies reveal a direct correlation between histone modifications and the structural stability of higher order chromatin assembly.

Biochemistry of malathion resistance in a strain of Cimex lectularius resistant to organophosphorus compounds.

The penetration of (14)C-labelled malathion was found to be similar in two bedbug strains, of which one was susceptible and the other moderately resistant to a range of organophosphorus insecticides. The latter strain was especially resistant to malathion and fenchlorphos, but was not resistant to organophosphates or (significantly) to organochlorine insecticides. There was no difference in acetylcholinesterase activity or sensitivity, or in total esterase activity (using 1- or 2-naphthyl acetates as substrates). In vitro experiments on malathion metabolism showed about 17% greater degradation in the resistant strain, demethyl malathion and malathion diacid being the main products.