Effectiveness of Live Health Professional-Led Group eHealth Interventions for Adult Mental Health: Systematic Review of Randomized Controlled Trials.

BACKGROUND: The COVID-19 pandemic has had adverse impacts on mental health and substance use worldwide. Systematic reviews suggest eHealth interventions can be effective at addressing these problems. However, strong positive eHealth outcomes are often tied to the intensity of web-based therapist guidance, which has time and cost implications that can make the population scale-up of more effective interventions difficult. A way to offset cost while maintaining the intensity of therapist guidance is to offer eHealth programs to groups rather than more standard one-on-one formats. OBJECTIVE: This systematic review aims to assess experimental evidence for the effectiveness of live health professional-led group eHealth interventions on mental health, substance use, or bereavement among community-dwelling adults. Within the articles selected for our primary aim, we also seek to examine the impact of interventions that encourage physical activity compared with those that do not. METHODS: Overall, 4 databases (MEDLINE, CINAHL, PsycINFO, and the Cochrane Library) were searched in July 2020. Eligible studies were randomized controlled trials (RCTs) of eHealth interventions led by health professionals and delivered entirely to adult groups by videoconference, teleconference, or webchat. Eligible studies reported mental health, substance use, or bereavement as primary outcomes. The results were examined by outcome, eHealth platform, and intervention length. Postintervention data were used to calculate effect size by study. The findings were summarized using the Synthesis Without Meta-Analysis guidelines. Risk of bias was assessed using the Cochrane Collaboration Tool. RESULTS: Of the 4099 identified studies, 21 (0.51%) RCTs representing 20 interventions met the inclusion criteria. These studies examined mental health outcomes among 2438 participants (sample size range: 47-361 participants per study) across 7 countries. When effect sizes were pooled, live health professional-led group eHealth interventions had a medium effect on reducing anxiety compared with inactive (Cohen d=0.57) or active control (Cohen d=0.48), a medium to small effect on reducing depression compared with inactive (Cohen d=0.61) or active control (Cohen d=0.21), and mixed effects on mental distress and coping. Interventions led by videoconference, and those that provided 8-12 hours of live health professional-led group contact had more robust effects on adult mental health. Risk of bias was high in 91% (19/21) of the studies. Heterogeneity across interventions was significant, resulting in low to very low quality of evidence. No eligible RCT was found that examined substance use, bereavement, or physical activity. CONCLUSIONS: Live eHealth group interventions led by health professionals can foster moderate improvements in anxiety and moderate to small improvements in depression among community-based adults, particularly those delivered by videoconference and those providing 8-12 hours of synchronous engagement. TRIAL REGISTRATION: PROSPERO CRD42020187551; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=187551. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1186/s13643-020-01479-3.

Celiac disease gene expression data can be used to classify biopsies along the Marsh score severity scale.

BACKGROUND AND AIM: The diagnosis of celiac disease autoimmune pathology relies on the subjective histological assignment of biopsies into Marsh score categories. It is hypothesized that Marsh score categories have unique gene expression signatures. The aims were as follows: first, to develop a celiac disease quantitative reverse transcription-polymerase chain reaction (RT-PCR) array; second, define gene expression signatures associated with Marsh score categories; and third, develop equations that classify biopsies into Marsh score categories and to monitor the efficacy of patient treatment. METHODS: Gene targets for inclusion in the celiac RT-PCR (qRT-PCR) array were identified using systematic analysis of published celiac transcriptomic data. The array was used to assess the gene expression associated with histological changes in duodenal biopsies obtained from adult patients. Finally, Marsh score classification equations were defined using discriminant analysis. RESULTS: The array contained 87 genes. The expression of 26 genes were significantly (p < 0.06) associated with the discrete Marsh score categories. As the Marsh score pathology of biopsies increased, there was a progression of innate immune gene expression through adaptive Th1-specific gene expression with a concurrent decrease in intestinal structural gene expression in high Marsh score samples. These 26 genes were used to define classification equations that accounted for 99% of the observed experimental variation and which could classify biopsies into Marsh score categories and monitor patient treatment progression. CONCLUSIONS: This proof-of-concept study successfully developed a celiac RT-PCR array and has provided evidence that discriminant equations defined using gene expression data can objectively and accurately classify duodenal biopsies into Marsh score categories.

Measurement of Internal pH in Helicobacter pylori by Using Green Fluorescent Protein Fluorimetry.

Helicobacter pylori is an organism known to colonize the normal human stomach. Previous studies have shown that the bacterium does this by elevating its periplasmic pH via the hydrolysis of urea. However, the value of the periplasmic pH was calculated indirectly from the proton motive force equation. To measure the periplasmic pH directly in H. pylori, we fused enhanced green fluorescent protein (EGFP) to the predicted twin-arginine signal peptides of HydA and KapA from H. pylori and TorA from Escherichia coli The fusion proteins were expressed in the H. pylori genome under the control of the cagA promoter. Confocal microscopic and cell fractionation/immunoblotting analyses detected TorA-EGFP in the periplasm and KapA-EGFP in both the periplasm and cytoplasm, while the mature form of HydA-EGFP was seen at low levels in the periplasm, with major cytoplasmic retention of the precursor form. With H. pylori expressing TorA-EGFP, we established a system to directly measure periplasmic pH based on the pH-sensitive fluorimetry of EGFP. These measurements demonstrated that the addition of 5 mM urea has little effect on the periplasmic pH at a medium pH higher than pH 6.5 but rapidly increases the periplasmic pH to pH 6.1 at an acidic medium pH (pH 5.0), corresponding to the opening of the proton-gated channel, UreI, and confirming the basis of gastric colonization. Measurements of the periplasmic pH in an HP0244 (FlgS)-deficient mutant of H. pylori expressing TorA-EGFP revealed a significant loss of the urea-dependent increase in the periplasmic pH at an acidic medium pH, providing additional evidence that FlgS is responsible for recruitment of urease to the inner membrane in association with UreI.IMPORTANCEHelicobacter pylori has been identified as the major cause of chronic superficial gastritis and peptic ulcer disease. In addition, persistent infection with H. pylori, which, if untreated, lasts for the lifetime of an infected individual, predisposes one to gastric malignancies, such as adenocarcinoma and mucosa-associated lymphoid tissue (MALT) lymphoma. A unique feature of the neutralophilic bacterium H. pylori is its ability to survive in the extremely acidic environment of the stomach through its acid acclimation mechanism. The presented results on measurements of periplasmic pH in H. pylori based on fluorimetry of fully active green fluorescent protein fusion proteins exported with the twin-arginine translocase system provide a reliable and rapid tool for the investigation of acid acclimation in H. pylori.

Acid-regulated gene expression of Helicobacter pylori: Insight into acid protection and gastric colonization.

BACKGROUND: The pathogen Helicobacter pylori encounters many stressors as it transits to and infects the gastric epithelium. Gastric acidity is the predominate stressor encountered by the bacterium during initial infection and establishment of persistent infection. H. pylori initiates a rapid response to acid to maintain intracellular pH and proton motive force appropriate for a neutralophile. However, acid sensing by H. pylori may also serve as a transcriptional trigger to increase the levels of other pathogenic factors needed to subvert host defenses such as acid acclimation, antioxidants, flagellar synthesis and assembly, and CagA secretion. MATERIALS AND METHODS: Helicobacter pylori were acid challenged at pH 3.0, 4.5, 6.0 vs nonacidic pH for 4 hours in the presence of urea, followed by RNA-seq analysis and qPCR. Cytoplasmic pH was monitored under the same conditions. RESULTS: About 250 genes were induced, and an equal number were repressed at acidic pHs. Genes encoding for antioxidant proteins, flagellar structural proteins, particularly class 2 genes, T4SS/Cag-PAI, Fo F1 -ATPase, and proteins involved in acid acclimation were highly expressed at acidic pH. Cytoplasmic pH decreased from 7.8 at pHout of 8.0 to 6.0 at pHout of 3.0. CONCLUSIONS: These results suggest that increasing extracellular or intracellular acidity or both are detected by the bacterium and serve as a signal to initiate increased production of protective and pathogenic factors needed to counter host defenses for persistent infection. These changes are dependent on degree of acidity and time of acid exposure, triggering a coordinated response to the environment required for colonization.

Septin oligomerization regulates persistent expression of ErbB2/HER2 in gastric cancer cells.

Septins are a family of cytoskeletal GTP-binding proteins that assemble into membrane-associated hetero-oligomers and organize scaffolds for recruitment of cytosolic proteins or stabilization of membrane proteins. Septins have been implicated in a diverse range of cancers, including gastric cancer, but the underlying mechanisms remain unclear. The hypothesis tested here is that septins contribute to cancer by stabilizing the receptor tyrosine kinase ErbB2, an important target for cancer treatment. Septins and ErbB2 were highly over-expressed in gastric cancer cells. Immunoprecipitation followed by MS analysis identified ErbB2 as a septin-interacting protein. Knockdown of septin-2 or cell exposure to forchlorfenuron (FCF), a well-established inhibitor of septin oligomerization, decreased surface and total levels of ErbB2. These treatments had no effect on epidermal growth factor receptor (EGFR), emphasizing the specificity and functionality of the septin-ErbB2 interaction. The level of ubiquitylated ErbB2 at the plasma membrane was elevated in cells treated with FCF, which was accompanied by a decrease in co-localization of ErbB2 with septins at the membrane. Cathepsin B inhibitor, but not bafilomycin or lactacystin, prevented FCF-induced decrease in total ErbB2 by increasing accumulation of ubiquitylated ErbB2 in lysosomes. Therefore, septins protect ErbB2 from ubiquitylation, endocytosis and lysosomal degradation. The FCF-induced degradation pathway is distinct from and additive with the degradation induced by inhibiting ErbB2 chaperone Hsp90. These results identify septins as novel regulators of ErbB2 expression that contribute to the remarkable stabilization of the receptor at the plasma membrane of cancer cells and may provide a basis for the development of new ErbB2-targeting anti-cancer therapies.

A Synthesis of Exiguaquinol Dessulfate.

A concise and stereoselective synthesis of exiguaquinol dessulfate is described. Sequential application of a Diels-Alder cycloaddition, a desymmetrizing aldol addition, and a reductive Heck cyclization established most of the architecture of exiguaquinol, and a carefully choreographed introduction of the polar substituents afforded the title compound; unfortunately, naphthoquinol sulfation could not be achieved to deliver exiguaquinol. Our hypothesis regarding the configurational preference of the N-acyl hemiaminal, which was based upon an analysis of internal hydrogen-bonding interactions with polar functional groups, was proven correct. A late-stage intermediate did not demonstrate bactericidal activity against H. pylori cultures.

Phosphorylation-dependent and Phosphorylation-independent Regulation of Helicobacter pylori Acid Acclimation by the ArsRS Two-component System.

BACKGROUND: The pH-sensitive Helicobacter pylori ArsRS two-component system (TCS) aids survival of this neutralophile in the gastric environment by directly sensing and responding to environmental acidity. ArsS is required for acid-induced trafficking of urease and its accessory proteins to the inner membrane, allowing rapid, urea-dependent cytoplasmic and periplasmic buffering. Expression of ArsR, but not its phosphorylation, is essential for bacterial viability. The aim of this study was to characterize the roles of ArsS and ArsR in the response of H. pylori to acid. MATERIALS AND METHODS: Wild-type H. pylori and an arsR(D52N) phosphorylation-deficient strain were incubated at acidic or neutral pH. Gene and protein expression, survival, membrane trafficking of urease proteins, urease activity, and internal pH were studied. RESULTS: Phosphorylation of ArsR is not required for acid survival. ArsS-driven trafficking of urease proteins to the membrane in acid, required for recovery of internal pH, is independent of ArsR phosphorylation. ArsR phosphorylation increases expression of the urease gene cluster, and the loss of negative feedback in a phosphorylation-deficient mutant leads to an increase in total urease activity. CONCLUSIONS: ArsRS has a dual function in acid acclimation: regulation of urease trafficking to UreI at the cytoplasmic membrane, driven by ArsS, and regulation of urease gene cluster expression, driven by phosphorylation of ArsR. ArsS and ArsR work through phosphorylation-dependent and phosphorylation-independent regulatory mechanisms to impact acid acclimation and allow gastric colonization. Furthering understanding of the intricacies of acid acclimation will impact the future development of targeted, nonantibiotic treatment regimens.

Eradication of Helicobacter pylori Infection.

Helicobacter pylori infects about 50 % of the world's population, causing at a minimum chronic gastritis. A subset of infected patients will ultimately develop gastric or duodenal ulcer disease, gastric adenocarcinoma, or MALT (mucosa-associated lymphoid tissue) lymphoma. Eradication of H. pylori requires complex regimens that include acid suppression and multiple antibiotics. The efficacy of treatment using what were once considered standard regimens have declined in recent years, mainly due to widespread development of antibiotic resistance. Addition of bismuth to standard triple therapy regimens, use of alternate antibiotics, or development of alternative regimens using known therapies in novel combinations have improved treatment efficacy in specific populations, but overall success of eradication remains less than ideal. Novel regimens under investigation either in vivo or in vitro, involving increased acid suppression ideally with fewer antibiotics or development of non-antibiotic treatment targets, show promise for future therapy.

Differential skin test reactivity to pollens in pollen food allergy syndrome versus allergic rhinitis.

BACKGROUND: Pollen food allergy syndrome (PFAS), also called oral allergy syndrome, is a form of food allergy in which uncooked foods cause allergic symptoms generally limited to the oral mucosa. It occurs in a subset of patients with pollen allergy, although not all patients have prominent rhinitis symptoms. PFAS is related to antigenic similarity between the pollen and food allergen. OBJECTIVE: The size of skin test reactions in a group of subjects with pollen sensitivity with PFAS was compared with a group of subjects who were pollen sensitive and without PFAS. Self-reported rhinitis symptoms between the two groups were compared to identify if symptom severity differed. METHODS: Twenty subjects with PFAS and 20 subjects with seasonal allergic rhinitis without PFAS were enrolled in the study. All the subjects underwent standard skin-prick testing to a panel of common allergens, including select fresh fruits and vegetables. The subjects completed a Mini Rhinoconjunctivitis Quality of Life Questionnaire as part of their clinical evaluation. The subjects with PFAS and those without PFAS were compared statistically. RESULTS: The subjects with PFAS had significantly larger-sized skin-prick test results specific to pollens (p < 0.05). Despite the larger-sized skin-prick test results, the subjects with allergic rhinitis and PFAS reported milder nasal symptoms in relation to pollen skin test result size when compared with allergic rhinitis controls without PFAS. CONCLUSIONS: Our study outlined basic differences between two seemingly similar patient groups with a particularly striking discordance between skin test result sizes and rhinitis symptoms. This discordance should be explored further to increase mechanistic understanding of allergen cross-reactivity in PFAS.

Increased ILC2s in the eosinophilic nasal polyp endotype are associated with corticosteroid responsiveness.

Group 2 innate lymphoid cells (ILC2s) have recently been identified in human nasal polyps, but whether numbers of ILC2s differ by polyp endotype or are influenced by corticosteroid use is unknown. Here, we show that eosinophilic nasal polyps contained double the number of ILC2s vs. non-eosinophilic polyps. Polyp ILC2s were also reduced by 50% in patients treated with systemic corticosteroids. Further, using a fungal allergen challenge mouse model, we detected greatly reduced Th2 cytokine-producing and Ki-67+ proliferating lung ILC2s in mice receiving dexamethasone. Finally, ILC2 Annexin V staining revealed extensive apoptosis after corticosteroid treatment in vivo and in vitro. Thus, ILC2s are elevated in the eosinophilic nasal polyp endotype and systemic corticosteroid treatment correlated with reduced polyp ILC2s. Finally, allergen-challenged mice showed reduced ILC2s and increased ILC2 apoptosis after corticosteroid treatment suggesting that ILC2 may be responsive to corticosteroids in eosinophilic respiratory disease.

Supraesophageal reflux disease: a review of the literature.

Supraesophageal reflux disease (SERD), defined as reflux proximal to the upper esophageal sphincter, is a common cause of morbidity of the upper aerodigestive tract, including rhinitis, laryngitis, cough, postnasal drip, and throat clearing. Although SERD has a high prevalence, the ideal means of diagnosing and treating the disease remain poorly defined. Evolving pH monitoring technology and a body of literature with conflicting reports regarding the best means for measuring and interpreting supraesophageal acidic reflux complicates the diagnosis of SERD. Treatment options include empiric acid suppression therapy, lifestyle modification, and surgery. However, limited data regarding the effectiveness of these strategies vary between studies and patient populations. It is the goal of this article to summarize the presentation and pathogenesis of SERD and to integrate the evolving body of literature pertaining to diagnostic and treatment strategies.

Exploring the relationship between falls, fall-related psychological concerns, and personality traits in adults: A scoping review protocol.

Background and Aims: Personality traits, such as neuroticism and extraversion, are emerging as important predictors of falls. Despite their significance, existing fall prevention programs often overlook these traits, creating a notable research gap. This study aims to conduct a comprehensive scoping review to explore the existing literature on the relationships among personality traits, falls, and fall-related psychological concerns (FrPCs). Methods: This scoping review will adhere to the framework established by Arksey and O'Malley, incorporating extensions recommended by the Joanna Briggs Institute and using the PRISMA-ScR checklist. A thorough search strategy will be employed, aligning with the population, concept, and context (PCC) selection criteria. Electronic databases, including MEDLINE, APA PsycINFO, Web of Science, CINAHL, and SPORTDiscus, will be searched from their inception to the present. Additionally, a manual search of the reference lists of identified and relevant full-text articles will be conducted. Two independent reviewers will screen titles and abstracts, perform full-text reviews, and extract data from pertinent articles. Discussion: Personality traits are increasingly recognized as influential predictors of falls and related psychological concerns. This review aims to make a substantial contribution to the existing literature by being the first to comprehensively explore and provide a descriptive synthesis of the relationship between personality traits and falls, as well as FrPCs in adults. It is hoped that the outcomes of this review will enhance our comprehension of the role of personality traits in falls, potentially informing future research and strategies for this critical area of study. Scoping Review Registration: This scoping review protocol was registered with Open Science Framework (https://doi.org/10.17605/OSF.IO/KR74X).

Acid stress increases gene expression of proinflammatory cytokines in Madin-Darby canine kidney cells.

Metabolic acidosis is thought to exacerbate chronic kidney disease in part by stimulating the release of potentially injurious substances. To define the genes whose expression is affected by exposure to an acidic milieus, we examined the effect of exposure of MDCK cells to pH 7.4 and pH 7.0 for 24 h on gene expression using a canine derived microarray. Exposure to this pH stress for 24 h led to increased expression of 278 genes (2.2% of the transcriptome) by at least 2-fold and 60 of these (21%) were upregulated by >3-fold. On the other hand, 186 genes (1.5% of the transcriptome) were downregulated by at least 2-fold and 16 of these (9%) were downregulated by 3-fold or more. Ten percent of the genes upregulated by at least threefold encode proinflammatory cytokine proteins, including colony stimulating factor 2, chemokine ligand 7, chemokine ligand 20, chemokine ligand 8, and interleukin-1α. Two others encode metallopeptidases. The most highly upregulated gene encodes a protein, lubricin, shown to be important in preventing cartilage damage and in tissue injury or repair. Upregulation of four genes was confirmed by quantitative PCR. Housekeeping genes were not increased. To examine the effect of decreasing medium pH, we measured intracellular pH (pH(i)) using 2,7-bis (2-carboxyethyl)5-carboxyfluorescein. With extracellular pH (pH(o)) of 7.0, pH(i) fell and remained depressed. These findings suggest that a pH stress alone can increase renal expression of proinflammatory and other genes that contribute to renal injury.

Helicobacter pylori impedes acid-induced tightening of gastric epithelial junctions.

Gastric infection by Helicobacter pylori is the most common cause of ulcer disease and gastric cancer. The mechanism of progression from gastritis and inflammation to ulcers and cancer in a fraction of those infected is not definitively known. Significant acidity is unique to the gastric environment and is required for ulcer development. The interplay between gastric acidity and H. pylori pathogenesis is important in progression to advanced disease. The aim of this study was to characterize the impact of acid on gastric epithelial integrity and cytokine release and how H. pylori infection alters these responses. Human gastric epithelial (HGE-20) cells were grown on porous inserts, and survival, barrier function, and cytokine release were studied at various apical pH levels in the presence and absence of H. pylori. With apical acidity, gastric epithelial cells demonstrate increased barrier function, as evidenced by increased transepithelial electrical resistance (TEER) and decreased paracellular permeability. This effect is reduced in the presence of wild-type, but not urease knockout, H. pylori. The epithelial inflammatory response is also modulated by acidity and H. pylori infection. Without H. pylori, epithelial IL-8 release decreases in acid, while IL-6 release increases. In the presence of H. pylori, acidic pH diminishes the magnitude of the previously reported increase in IL-8 and IL-6 release. H. pylori interferes with the gastric epithelial response to acid, contributing to altered barrier function and inflammatory response. H. pylori diminishes acid-induced tightening of cell junctions in a urease-dependent manner, suggesting that local pH elevation promotes barrier compromise and progression to mucosal damage.

The role of ExbD in periplasmic pH homeostasis in Helicobacter pylori.

BACKGROUND: Helicobacter pylori, a neutralophile, colonizes the acidic environment of the human stomach by employing acid acclimation mechanisms that regulate periplasmic and cytoplasmic pH. The regulation of urease activity is central to acid acclimation. Inactive urease apoenzyme, UreA/B, requires nickel for activation. Accessory proteins UreE, F, G, and H are required for nickel insertion into apoenzyme. The ExbB/ExbD/TonB complex transfers energy from the inner to outer membrane, providing the driving force for nickel uptake. Therefore, the aim of this study was to determine the contribution of ExbD to pH homeostasis. MATERIALS AND METHODS: A nonpolar exbD knockout was constructed and survival, growth, urease activity, and membrane potential were determined in comparison with wildtype. RESULTS: Survival of the ΔexbD strain was significantly reduced at pH 3.0. Urease activity as a function of pH and UreI activation was similar to the wildtype strain, showing normal function of the proton-gated urea channel, UreI. The increase in total urease activity over time in acid seen in the wildtype strain was abolished in the ΔexbD strain, but recovered in the presence of supraphysiologic nickel concentrations, demonstrating that the effect of the ΔexbD mutant is due to loss of a necessary constant supply of nickel. In acid, ΔexbD also decreased its ability to maintain membrane potential and periplasmic buffering in the presence of urea. CONCLUSIONS: ExbD is essential for maintenance of periplasmic buffering and membrane potential by transferring energy required for nickel uptake, making it a potential nonantibiotic target for H. pylori eradication.

Recurrent fevers and failure to thrive in an infant.

We describe a 2-year old boy with consanguineous parents who recently emigrated from India and presented with oral ulcers and lymphadenopathy. He also had a history of recurrent fevers, polyarticular arthritis, chronic diarrhea, failure to thrive, and developmental delay. Infectious workup revealed herpes simplex virus 1 viremia and radiological evaluation revealed osteopenia and erosions involving multiple joints. We describe the immunologic and genetic evaluation of this patient and discuss the diagnostic and therapeutic approach to an infant with recurrent fevers.

Association between sociodemographic factors and mobility limitation among older adults: a systematic review and meta-analysis protocol.

BACKGROUND: Mobility is an independent predictor of physical functionality, healthy ageing, and quality of life. Various literatures have associated mobility limitation in older adulthood with demographic and socioeconomic factors. Hence, we propose a systematic review and meta-analysis to synthesise the association between sociodemographic factors and mobility limitations in older adults. METHODS AND ANALYSES: This protocol was written according to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) guidelines. We will perform a comprehensive search of all observational studies that assessed the relationship between age, gender, race, place, education, income, occupation, social status, and walking distance, time, or speed. Electronic databases (MEDLINE, Web of Science, EMBASE, CINAHL, AgeLine, and SPORTDiscus) will be searched from inception to 28 February 2023. We will supplement the database search by manually searching the reference lists of all identified and relevant full-text articles. Two independent reviewers will be responsible for screening articles, data extraction, and assessment of bias. We will appraise the study quality and risk of bias using the Prediction Model Risk of Bias Assessment Tool (PROBAST). A meta-analysis will be considered if data from the selected studies are homogeneous, otherwise, a narrative synthesis of the extracted data will be presented. DISCUSSION: Mobility limitation leads to frequent falls, dependency, morbidity, and death among older adults. This review is necessary, to identify and prioritise important sociodemographic factors during older adults' clinical assessment and policy development. It is the first phase of a multi-methods study seeking to develop a prognostic mobility trajectory for community-dwelling older adults. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022298570.

Determinants of Outdoor Time in Children and Youth: A Systematic Review of Longitudinal and Intervention Studies.

Spending more time outdoors can improve children's social and cognitive development, physical activity, and vision. Our systematic review summarized the determinants of outdoor time (OT) based on the social-ecological model. We searched nine databases: MEDLINE, APA PsycINFO, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), CINAHL, SPORTDiscus, ERIC, SocINDEX, and ProQuest Dissertations and Theses. To be included, studies needed to be quantitative and longitudinal, include ≥1 potential determinant of OT among 0- to 17-year-olds, and be published in English, French, Japanese, or Spanish. We extracted the authors, publication year, country, design, sample size, OT measures, follow-up period, potential determinants, main results, and potential moderators or mediators. Fifty-five studies examining 119 potential determinants met the inclusion criteria. OT was consistently higher in warmer seasons and among participants reporting more OT at baseline. All three interventions that included both parent sessions and additional resources to promote OT (e.g., specific advice and community guides) were effective. COVID-19 restrictions and sun safety interventions discouraging midday outdoor activities led to less OT. The quality of evidence was rated as weak for 46 studies. Most potential determinants were examined in ≤3 studies; thus, more longitudinal studies are needed to enable stronger conclusions about the consistency of evidence and meta-analyses.

Role of the Helicobacter pylori sensor kinase ArsS in protein trafficking and acid acclimation.

Helicobacter pylori survives and grows at low pHs via acid acclimation mechanisms that enable periplasmic pH homeostasis. Important components include a cytoplasmic urease; a pH-gated urea channel, UreI; and periplasmic α-carbonic anhydrase. To allow the rapid adjustment of periplasmic pH, acid acclimation components are recruited to the inner membrane in acid. The ArsRS two-component system, in an acid-responsive manner, controls the transcription of the urease gene cluster and α-carbonic anhydrase. The aim of this study is to determine the role of ArsS in protein trafficking as a component of acid acclimation. H. pylori wild-type and ΔarsS bacteria were incubated at acidic and neutral pHs. Intact bacteria, purified membranes, and total protein were analyzed by Western blotting and urease activity measurements. The total urease activity level was decreased in the ΔarsS strain, but the acid activation of UreI was unaffected. A 30-min acid exposure increased the level and activity of urease proteins at the membrane in the wild type but not in the ΔarsS strain. The urease levels and activity of the ΔarsS strain after a 90-min acid exposure were similar to those of the wild type. ArsS, in addition to its role in urease gene transcription, is also involved in the recruitment of urease proteins to the inner membrane to augment acid acclimation during acute acid exposure. Urease membrane recruitment following prolonged acid exposure in the absence of ArsS was similar to that of the wild type, suggesting a compensatory mechanism, possibly regulated by FlgS, underscoring the importance of urease membrane recruitment and activation in periplasmic pH homeostasis.

A cis-encoded antisense small RNA regulated by the HP0165-HP0166 two-component system controls expression of ureB in Helicobacter pylori.

Expression of urease is essential for gastric colonization by Helicobacter pylori. The increased level of urease in gastric acidity is due, in part, to acid activation of the two-component system (TCS) consisting of the membrane sensor HP0165 and its response regulator, HP0166, which regulates transcription of the seven genes of the urease gene cluster. We now find that there are two major ureAB transcripts: a 2.7-kb full-length ureAB transcript and a 1.4-kb truncated transcript lacking 3' ureB. Acidic pH (pH 4.5) results in a significant increase in transcription of ureAB, while neutral pH (pH 7.4) increases the truncated 1.4-kb transcript. Northern blot analysis with sense RNA and strand-specific oligonucleotide probes followed by 5' rapid amplification of cDNA ends detects an antisense small RNA (sRNA) encoded by the 5' ureB noncoding strand consisting of ∼290 nucleotides (5'ureB-sRNA). Deletion of HP0165 elevates the level of the truncated 1.4-kb transcript along with that of the 5'ureB-sRNA at both pH 7.4 and pH 4.5. Overexpression of 5'ureB-sRNA increases the 1.4-kb transcript, decreases the 2.7-kb transcript, and decreases urease activity. Electrophoretic mobility shift assay shows that unphosphorylated HP0166 binds specifically to the 5'ureB-sRNA promoter. The ability of the HP0165-HP0166 TCS to both increase and decrease ureB expression at low and high pHs, respectively, facilitates gastric habitation and colonization over the wide range of intragastric pHs experienced by the organism.