Effectiveness of psychological intervention in improving adolescents' oral health: A systematic review and meta-analysis.

OBJECTIVES: This systematic review aimed to evaluate the effectiveness of psychological interventions in improving oral health behaviors and status among adolescents. SOURCES: A comprehensive search was conducted in the following six electronic databases, PubMed, Ovid Medline, Ovid Embase, Cochrane Library, APA PsycINFO (ProQuest) and Web of Science. STUDY SELECTION: The PICO format was used to select eligible studies. Population was adolescents 12 to 18 years old. Intervention was psychological interventions based on psychological theories or models. Comparison was conventional oral health education or negative control. Outcomes were oral health-related behaviors, oral health status, oral health-related quality of life (OHRQoL), self-efficacy and psychological cognitive factors. The risk of bias tool used was RoB 2. DATA: Sixteen papers on 14 studies met the inclusion criteria. The studies were conducted in school or clinic settings. Regarding risk of bias, most studies had some concerns and the others had a high risk. The psychological interventions improved adolescent's oral hygiene and periodontal status in the short-term (up to 6 months), with the overall SMD = -0.97 (-1.45, -0.49) in plaque level and SMD = -1.18 (-2.32, -0.04) in periodontal status. No significant difference in plaque level was found in the long-term (12 to 24 months), with the overall SMD = -0.31 (-0.64, 0.02). There was improvement in OHRQoL in the short-term, with the overall SMD = 1.04 (0.34, 1.73). Additionally, significant differences were found regarding self-efficacy, oral health-related behaviors (tooth brushing and dental flossing) and psychological cognitive factors between the intervention group and control group (all p < 0.05) in the short-term. Due to the heterogeneity of the studies, meta-analysis could not be conducted in the above three outcome measurements. CONCLUSIONS: Low certainty of evidence shows that psychological intervention is effective in improving adolescents' oral hygiene in short-term. In addition, very low certainty of evidence was found in improving periodontal status, self-efficacy, oral health-related behaviors, psychological cognitive factors, and OHRQoL in short-term. CLINICAL SIGNIFICANCE: By targeting the psychological process and cognitive factors of oral health-related behaviors among adolescents, psychological interventions have the potential to improve oral health behaviours and promote oral health among adolescents. Implementing evidence-based psychological interventions in dental practice can lead to more comprehensive and effective dental care for adolescents.

Call to Action: Quality and Simulation Professionals Should Collaborate.

SUMMARY STATEMENT: Simulation is underutilized as a tool to improve healthcare quality and safety despite many examples of its effectiveness to identify and remedy quality and safety problems, improve teamwork, and improve various measures of quality and safety that are important to healthcare organizations, eg, patient safety indicators. We urge quality and safety and simulation professionals to collaborate with their counterparts in their organizations to employ simulation in ways that improve the quality and safety of care of their patients. These collaborations could begin through initiating conversations among the quality and safety and simulation professionals, perhaps using this article as a prompt for discussion, identifying one area in need of quality and safety improvement for which simulation can be helpful, and beginning that work.

Race norming and biases in surgical oncology care.

Disparities in surgical oncology care may be due to race/ethnicity. Race norming, defined as the adjustment of medical assessments based on an individual's race/ethnicity, and implicit bias are specifically explored in this focused systematic review. We aim to examine how race norming and bias impact oncologic care and postsurgical outcomes, particularly in Black patient populations, while providing potential strategies to improve equitable and inclusive care.

Attenuated responses to attention-modulating drugs in the neuroligin-3R451C mouse model of autism.

Attention deficits are frequently reported within the clinical autism population. Despite not being a core diagnostic feature, some aetiological theories place atypical attention at the centre of autism development. Drugs used to treat attention dysfunction are therefore increasingly prescribed to autistic patients, though currently off-label with uncertain efficacy. We utilised a rodent-translated touchscreen test of sustained attention in mice carrying an autism-associated R451C mutation in the neuroligin-3 gene (Nlgn3R451C). In doing so, we replicated their cautious but accurate response profile and probed it using two widely prescribed attention-modulating drugs: methylphenidate (MPH) and atomoxetine (ATO). In wild-type mice, acute administration of MPH (3 mg/kg) promoted impulsive responding at the expense of accuracy, while ATO (3 mg/kg) broadly reduced impulsive responding. These drug effects were absent in Nlgn3R451C mice, other than a small reduction in blank touches to the screen following ATO administration. The absence of drug effects in Nlgn3R451C mice likely arises from their altered behavioural baseline and underlying neurobiology, highlighting caveats to the use of classic attention-modulating drugs across disorders and autism subsets. It further suggests that altered dopaminergic and/or norepinephrinergic systems may drive behavioural differences in the Nlgn3R451C mouse model of autism, supporting further targeted investigation.

Typhoid fever: the challenging diagnosis of a pseudo-outbreak in Benguet, Philippines.

Objective: The event-based surveillance and response report from the municipality of Buguias in the Philippines covering the period 1 January to 29 October 2022 indicated an unusual increase in the number of typhoid cases that surpassed the epidemic threshold for consecutive weeks. An investigation was conducted to confirm the existence of an outbreak, identify the source(s) of transmission and recommend prevention and control measures. Methods: The investigation employed a descriptive design. Medical records were reviewed to verify diagnoses and to identify cases that met case definitions. Key informant interviews were conducted to identify possible sources of transmission and investigate the reporting of cases in the Philippine Integrated Disease Surveillance and Response (PIDSR) system. Results: A total of 220 cases of typhoid fever were captured by the PIDSR system. Of the 208 suspected cases that were reviewed, only 15 (7.2%) met the case definition used in this investigation. Fourteen of these 15 verified cases were interviewed; five (35.7%) were farmers and 13 (92.8%) reported using springs as their main water source and source of drinking-water. Reporting of cases in the PIDSR system was largely based on the final chart diagnosis or a positive Typhidot or Tubex rapid diagnostic test result. The PIDSR case definition was not followed in the reporting of cases. Discussion: This study provides evidence of endemicity of typhoid fever in Buguias, Benguet, Philippines. However, from January to October 2022, cases were overreported by the surveillance system. Medical record reviews showed that most reported suspected cases did not meet case definition criteria. This finding emphasizes the need to improve typhoid guidelines with regards to diagnosis using rapid diagnostic tests and to investigate the cost-effectiveness of making confirmatory laboratory tests for typhoid available in the Philippines.

Changing the default meal option at university events to reduce harmful environmental impacts: Six randomized controlled trials.

Animal agriculture is a leading contributor to greenhouse gas emissions and other harmful environmental impacts, which underscores the need to shift away from the consumption of animal-based products. One promising nudge intervention is making plant-based meals the default option, so we tested this approach at six different university events across four academic institutions for effecting sustainable dietary change. Event attendees pre-selected their meal on one of two randomly assigned RSVP forms: one with a plant-based default and one with a meal with meat default. The results from our randomized controlled trial showed that participants had a 43-percentage point greater probability of selecting the plant-based meal when it was indicated as the default option. This effect was similar across events and academic institutions, which indicates that this default intervention is generalizable and can be successfully implemented at university events. The combined effect of using plant-based defaults at these six events was an estimated reduction of 104,387 kg of CO2 emissions, 299.9 m2 of land use, 959.0 g of nitrogen use, and 259.5 g of phosphorus use, which represent roughly 45-46.2% reductions in harmful environmental impacts relative to the meals chosen when using a meat default. Given the significance and magnitude of these environmental benefits, our results support the widespread implementation of plant-based defaults for helping universities improve their sustainability.

Multiplexed Profiling of CDK Kinase Activities in Tumor Biopsies with Fluorescent Peptide Biosensors.

Detection of disease biomarkers constitutes a major challenge for the development of personalized and predictive diagnostics as well as companion assays. Protein kinases (PKs) involved in the coordination of cell cycle progression and proliferation that are hyperactivated in human cancers constitute attractive pharmacological targets and relevant biomarkers. Although it is relatively straightforward to assess the relative abundance of PKs in a biological sample, there is not always a direct correlation with enzymatic activity, which is regulated by several posttranslational mechanisms. Studies of relative abundance therefore convey limited information, and the lack of selective, sensitive, and standardized tools together with the inherent complexity of biological samples makes it difficult to quantify PK activities in physio-pathological tissues. To address this challenge, we have developed a toolbox of fluorescent biosensors that report on CDK activities in a sensitive, selective, dose-dependent, and quantitative fashion, which we have implemented to profile CDK activity signatures in cancer cell lines and biopsies from human tumors. In this study, we report on a standardized and calibrated biosensing approach to quantify CDK1,2,4, and 6 activities simultaneously through a combination of four different biosensors in a panel of 40 lung adenocarcinoma and 40 follicular lymphoma samples. CDK activity profiling highlighted two major patterns which were further correlated with age, sex of patients, tumor size, grade, and genetic and immunohistochemical features of the biopsies. Multiplex CDKACT biosensing technology provides new and complementary information relative to current genetic and immunohistochemical characterization of tumor biopsies, which will be useful for diagnostic purposes, potentially guiding therapeutic decision. These fluorescent peptide biosensors offer promise for personalized diagnostics based on kinase activity profiling.

Operationalisation of Successful Ageing in the Oral Health Context: A Citation Analysis.

OBJECTIVES: The rapidly ageing world has placed considerable demands on health and social care. To address this, the World Health Organization (WHO) and United Nations (UN) have declared action for this decade (2021-2030) to promote healthy ageing. Operationalisation of successful ageing in the oral health context in terms of its dimensions and their interconnectedness was determined. METHODS: A citation analysis was conducted following a scoping review to determine oral health's relationship with 5 key dimensions of successful ageing. This included examining the occurrence and co-occurrence amongst dimensions and over time. Specific consideration of citations by country, journal type, and authors through overlay visualisation was performed to map their interconnectedness. RESULTS: The scoping review identified 263 publications covering 1730 specific terms. There was a growing interest in successful ageing in the oral health context, mostly in the past decade (2010 onwards; 65.8%, 173 publications). The dimension of key consideration was "health and ADLs" (activities of daily living); this dimension appeared in 97.3% of publications (n = 256) and was found earliest to emerge, with the greatest link strengths compared to other dimensions. Country-level variations in citation data were observed, and there was good citation interconnectedness between them. Key oracles for dissemination have been medical rather than dental-specific journals. Amongst authors, there was considerable interconnectedness in the field. CONCLUSIONS: Findings highlight how successful ageing in the oral health context has been studied, with implications for addressing the significance of oral health to older peoples' lives in line with the WHO and UN's agenda. Citation analyses identified the "known unknowns" area for further consideration, and these findings have the potential to inform how dental research may best move forward with the successful ageing agenda to bring about translational impact.

Exploring the role of blood pressure in the black-white disparity in cardiovascular disease mortality: a causal mediation analysis.

BACKGROUND: Cardiovascular diseases (CVDs) are the leading cause of death in the USA, and high blood pressure is a major risk factor for CVD. Despite the overall declining rates of CVD mortality in the USA in recent years, marked disparities between racial and ethnic groups persist, with black adults having a higher mortality rate than white adults. We investigated the extent to which blood pressure mediated the black-white disparity in CVD mortality. METHODS: Data came from the Multi-Ethnic Study of Atherosclerosis, a diverse longitudinal cohort. We included 1325 black and 2256 white community-based adults aged 45-80 years free of clinical CVD at baseline and followed for 14 years. We used causal mediation analysis to estimate the effect of race on CVD mortality that was mediated through blood pressure. RESULTS: Black participants had a higher hazard of dying from CVD compared with white participants (adjusted hazard ratio (HR): 1.28 (95% CI 0.88, 1.88)), though estimates were imprecise. Systolic blood pressure mediated 27% (HR: 1.02, 95% CI 1.00, 1.06) and diastolic blood pressure mediated 55% (HR: 1.07, 95% CI 1.01, 1.10) of the racial disparities in CVD mortality between white and black participants. Mediation effects were present in men but not in women. CONCLUSIONS: We found that black-white differences in blood pressure partially explain the observed black-white disparity in CVD mortality, particularly among men. Our findings suggest that public health interventions targeting high blood pressure prevention and management could be important strategies for reducing racial disparities in CVD mortality.

Ethaverine and Papaverine Target Cyclin-Dependent Kinase 5 and Inhibit Lung Cancer Cell Proliferation and Migration.

CDK5 kinase plays a central role in the regulation of neuronal functions, and its hyperactivation has been associated with neurodegenerative pathologies and more recently with several human cancers, in particular lung cancer. However, ATP-competitive inhibitors targeting CDK5 are poorly selective and suffer limitations, calling for new classes of inhibitors. In a screen for allosteric modulators of CDK5, we identified ethaverine and closely related derivative papaverine and showed that they inhibit cell proliferation and migration of non small cell lung cancer cell lines. Moreover the efficacy of these compounds is significantly enhanced when combined with the ATP-competitive inhibitor roscovitine, suggesting an additive dual mechanism of inhibition targeting CDK5. These compounds do not affect CDK5 stability, but thermodenaturation studies performed with A549 cell extracts infer that they interact with CDK5 in cellulo. Furthermore, the inhibitory potentials of ethaverine and papaverine are reduced in A549 cells treated with siRNA directed against CDK5. Taken together, our results provide unexpected and novel evidence that ethaverine and papaverine constitute promising leads that can be repurposed for targeting CDK5 in lung cancer.

Social Isolation, Brain Food Cue Processing, Eating Behaviors, and Mental Health Symptoms.

Importance: Perceived social isolation is associated with negative health outcomes, including increased risk for altered eating behaviors, obesity, and psychological symptoms. However, the underlying neural mechanisms of these pathways are unknown. Objective: To investigate the association of perceived social isolation with brain reactivity to food cues, altered eating behaviors, obesity, and mental health symptoms. Design, Setting, and Participants: This cross-sectional, single-center study recruited healthy, premenopausal female participants from the Los Angeles, California, community from September 7, 2021, through February 27, 2023. Exposure: Participants underwent functional magnetic resonance imaging while performing a food cue viewing task. Main Outcomes and Measures: The main outcomes included brain reactivity to food cues, body composition, self-reported eating behaviors (food cravings, reward-based eating, food addiction, and maladaptive eating behaviors), and mental health symptoms (anxiety, depression, positive and negative affect, and psychological resilience). Results: The study included 93 participants (mean [SD] age, 25.38 [7.07] years). Participants with higher perceived social isolation reported higher fat mass percentage, lower diet quality, increased maladaptive eating behaviors (cravings, reward-based eating, uncontrolled eating, and food addiction), and poor mental health (anxiety, depression, and psychological resilience). In whole-brain comparisons, the higher social isolation group showed altered brain reactivity to food cues in regions of the default mode, executive control, and visual attention networks. Isolation-related neural changes in response to sweet foods correlated with various altered eating behaviors and psychological symptoms. These altered brain responses mediated the connection between social isolation and maladaptive eating behaviors (ß for indirect effect, 0.111; 95% CI, 0.013-0.210; P = .03), increased body fat composition (ß, -0.141; 95% CI, -0.260 to -0.021; P = .02), and diminished positive affect (ß, -0.089; 95% CI, -0.188 to 0.011; P = .09). Conclusions and Relevance: These findings suggest that social isolation is associated with altered neural reactivity to food cues within specific brain regions responsible for processing internal appetite-related states and compromised executive control and attentional bias and motivation toward external food cues. These neural responses toward specific foods were associated with an increased risk for higher body fat composition, worsened maladaptive eating behaviors, and compromised mental health. These findings underscore the need for holistic mind-body-directed interventions that may mitigate the adverse health consequences of social isolation.

Examination of community-level interventions addressing early childhood obesity in Los Angeles County.

Objective: To help inform decisions regarding the equitable implementation of obesity interventions, we examined whether interventions were equitably reaching the most vulnerable communities, identified communities that received fewer interventions than expected, and estimated the effect of 'dose' of interventions on obesity prevalence. Methods: We created a database to identify and characterize obesity-related interventions implemented in Los Angeles County from 2005 to 2015 linked to community-level sociodemographic and obesity prevalence data. We ran generalized linear models with a Gamma distribution and log link to determine if interventions were directed toward vulnerable communities and to identify communities that received fewer interventions than expected. We ran fixed-effects models to estimate the association between obesity prevalence and intervention strategy count among preschool-aged children enrolled in the Special Supplemental Nutrition Assistance Program for Women Infants and Children. Results: We found that interventions targeted vulnerable communities with high poverty rates and percentages of minority residents. The small cluster of communities that received fewer interventions than expected tended to have poor socioeconomic profiles. Communities which received more intervention strategies saw greater declines in obesity prevalence (ß = -0.023; 95 % CI: -0.031, -0.016). Conclusions: It is important to determine if interventions are equitably reaching vulnerable populations as resources to tackle childhood obesity become available. Evaluating the population impact of multiple interventions implemented simultaneously presents methodological challenges in measuring intervention dose and identifying cost-effective strategies. Addressing these challenges must be an important research priority as community-wide interventions involve multiple intervention strategies to reduce health disparities.

Lessons Learned From TranslateCovid, a Multilingual Online Resource Hub for Asian American and Pacific Islander Communities and Beyond.

The COVID-19 pandemic exacerbated health disparities among immigrant communities. Delivering accurate information and addressing misinformation on protective measures and vaccination to linguistically disadvantaged groups was critical for mitigating the effects of the pandemic. One group that was especially vulnerable to miscommunication about COVID-19 was non-native English-speaking immigrants. To address these disparities, the Asian American Studies Center and the Fielding School of Public Health at the University of California, Los Angeles, partnered to create a multilingual resource hub, TranslateCovid.org, to disseminate credible and reliable information about COVID-19 safety measures, the science behind the vaccines, and vaccine safety. We identified >1300 verified resources in 60 languages from government, academic, and nonprofit organizations and reposted them on the TranslateCovid website. We also developed public service announcement videos on handwashing, use of face masks, and social distancing in 10 languages and a fact sheet for frequently asked questions in 20 languages. We used a participatory approach to develop strategies for disseminating these resources. We discuss lessons learned, including strategies for forming government, community, and academic partnerships to support the timely development and dissemination of information. We conclude with a discussion on the unique role of universities in promoting equitable access to public health resources among immigrant communities in times of crisis.

ERMA (TMEM94) is a P-type ATPase transporter for Mg2+ uptake in the endoplasmic reticulum.

Intracellular Mg2+ (iMg2+) is bound with phosphometabolites, nucleic acids, and proteins in eukaryotes. Little is known about the intracellular compartmentalization and molecular details of Mg2+ transport into/from cellular organelles such as the endoplasmic reticulum (ER). We found that the ER is a major iMg2+ compartment refilled by a largely uncharacterized ER-localized protein, TMEM94. Conventional and AlphaFold2 predictions suggest that ERMA (TMEM94) is a multi-pass transmembrane protein with large cytosolic headpiece actuator, nucleotide, and phosphorylation domains, analogous to P-type ATPases. However, ERMA uniquely combines a P-type ATPase domain and a GMN motif for ERMg2+ uptake. Experiments reveal that a tyrosine residue is crucial for Mg2+ binding and activity in a mechanism conserved in both prokaryotic (mgtB and mgtA) and eukaryotic Mg2+ ATPases. Cardiac dysfunction by haploinsufficiency, abnormal Ca2+ cycling in mouse Erma+/- cardiomyocytes, and ERMA mRNA silencing in human iPSC-cardiomyocytes collectively define ERMA as an essential component of ERMg2+ uptake in eukaryotes.

Survival and cancer recurrence after short-course perioperative probiotics in a randomized trial.

BACKGROUND & AIMS: The long-term impact of perioperative probiotics remains understudied while mounting evidence links microbiome and oncogenesis. Therefore, we analyzed overall survival and cancer recurrence among patients enrolled in a randomized trial of perioperative probiotics. METHODS: 6-year follow-up of surgical patients participating in a randomized trial evaluating short-course perioperative oral probiotic VSL#3 (n = 57) or placebo (n = 63). RESULTS: Study groups did not differ in age, preoperative hemoglobin, ASA status, and Charlson comorbidity index. There was a significant difference in preoperative serum albumin (placebo group 4.0 ± 0.1 vs. 3.7 ± 0.1 g/dL in the probiotic group, p = 0.030). Thirty-seven deaths (30.8 %) have occurred during a median follow-up of 6.2 years. Overall survival stratified on preoperative serum albumin and surgical specialty was similar between groups (p = 0.691). Age (aHR = 1.081, p = 0.001), serum albumin (aHR = 0.162, p = 0.001), and surgical specialty (aHR = 0.304, p < 0.001) were the only predictors of overall survival in the multivariate model, while the placebo/probiotic group (aHR = 0.808, p = 0.726) was not predictive. The progression rate among cancer patients was similar in the probiotic group (30.3 %, 10/33) compared to the placebo group (21.2 %, 7/33; p = 0.398). The progression-free survival was not significantly different (unstratified p = 0.270, stratified p = 0.317). CONCLUSIONS: Perioperative short-course use of VSL#3 probiotics does not influence overall or progression-free survival after complex surgery for visceral malignancy.

Long-term stability of jaw reconstruction with microvascular bone flaps: A prospective longitudinal study.

OBJECTIVES: Microvascular bone flap jaw reconstruction has achieved satisfactory clinical outcomes. However, little is known about the long-term stability of the reconstructed jaw. This prospective longitudinal study aimed to investigate the long-term stability of jaw reconstruction and factors that were associated with it. METHODS: Patients with successful computer-assisted osseous free-flap jaw reconstruction in the Department of Oral and Maxillofacial Surgery, Queen Mary Hospital, Hong Kong were recruited for this prospective longitudinal study. The three-dimensional jaw models at the pre-operative plan, post-operative 1-month, and 2 years were aligned and compared. RESULTS: A total of 69 patients were recruited, among which 48 patients were available for the long-term analysis. Compared to 1-month after surgery, further deviation from the pre-operative plan was observed at post-operative 2 years. Lack of accuracy in surgery, segmental mandible resection especially with the involvement of mandible angles, and post-operative radiation therapy were identified as the significant factors affecting the positional stability of the reconstructed jaw (p < 0.05). Stable reconstruction was observed in the subgroup analysis of patients without post-operative radiation therapy. CONCLUSION: Up to the best of our knowledge, this is the first prospective longitudinal study reporting the long-term stability of jaw reconstruction and its affecting factors. Our data demonstrated that the reconstructed jaw position lacked stability over the postoperative period. How to improve long-term stability of reconstructed jaw thus optimize the functional outcomes warrants further studies.

Spatial enhancer activation influences inhibitory neuron identity during mouse embryonic development.

The mammalian telencephalon contains distinct GABAergic projection neuron and interneuron types, originating in the germinal zone of the embryonic basal ganglia. How genetic information in the germinal zone determines cell types is unclear. Here we use a combination of in vivo CRISPR perturbation, lineage tracing and ChIP-sequencing analyses and show that the transcription factor MEIS2 favors the development of projection neurons by binding enhancer regions in projection-neuron-specific genes during mouse embryonic development. MEIS2 requires the presence of the homeodomain transcription factor DLX5 to direct its functional activity toward the appropriate binding sites. In interneuron precursors, the transcription factor LHX6 represses the MEIS2-DLX5-dependent activation of projection-neuron-specific enhancers. Mutations of Meis2 result in decreased activation of regulatory enhancers, affecting GABAergic differentiation. We propose a differential binding model where the binding of transcription factors at cis-regulatory elements determines differential gene expression programs regulating cell fate specification in the mouse ganglionic eminence.

A POLR3B-variant reveals a Pol III transcriptome response dependent on La protein/SSB.

RNA polymerase III (Pol III, POLR3) synthesizes tRNAs and other small non-coding RNAs. Human POLR3 pathogenic variants cause a range of developmental disorders, recapitulated in part by mouse models, yet some aspects of POLR3 deficiency have not been explored. We characterized a human POLR3B:c.1625A>G;p.(Asn542Ser) disease variant that was found to cause mis-splicing of POLR3B. Genome-edited POLR3B1625A>G HEK293 cells acquired the mis-splicing with decreases in multiple POLR3 subunits and TFIIIB, although display auto-upregulation of the Pol III termination-reinitiation subunit POLR3E. La protein was increased relative to its abundant pre-tRNA ligands which bind via their U(n)U-3'-termini. Assays for cellular transcription revealed greater deficiencies for tRNA genes bearing terminators comprised of 4Ts than of ≥5Ts. La-knockdown decreased Pol III ncRNA expression unlinked to RNA stability. Consistent with these effects, small-RNAseq showed that POLR3B1625A>G and patient fibroblasts express more tRNA fragments (tRFs) derived from pre-tRNA 3'-trailers (tRF-1) than from mature-tRFs, and higher levels of multiple miRNAs, relative to control cells. The data indicate that decreased levels of Pol III transcripts can lead to functional excess of La protein which reshapes small ncRNA profiles revealing new depth in the Pol III system. Finally, patient cell RNA analysis uncovered a strategy for tRF-1/tRF-3 as POLR3-deficiency biomarkers.

Loss of the endoplasmic reticulum protein Tmem208 affects cell polarity, development, and viability.

Nascent proteins destined for the cell membrane and the secretory pathway are targeted to the endoplasmic reticulum (ER) either posttranslationally or cotranslationally. The signal-independent pathway, containing the protein TMEM208, is one of three pathways that facilitates the translocation of nascent proteins into the ER. The in vivo function of this protein is ill characterized in multicellular organisms. Here, we generated a CRISPR-induced null allele of the fruit fly ortholog CG8320/Tmem208 by replacing the gene with the Kozak-GAL4 sequence. We show that Tmem208 is broadly expressed in flies and that its loss causes lethality, although a few short-lived flies eclose. These animals exhibit wing and eye developmental defects consistent with impaired cell polarity and display mild ER stress. Tmem208 physically interacts with Frizzled (Fz), a planar cell polarity (PCP) receptor, and is required to maintain proper levels of Fz. Moreover, we identified a child with compound heterozygous variants in TMEM208 who presents with developmental delay, skeletal abnormalities, multiple hair whorls, cardiac, and neurological issues, symptoms that are associated with PCP defects in mice and humans. Additionally, fibroblasts of the proband display mild ER stress. Expression of the reference human TMEM208 in flies fully rescues the loss of Tmem208, and the two proband-specific variants fail to rescue, suggesting that they are loss-of-function alleles. In summary, our study uncovers a role of TMEM208 in development, shedding light on its significance in ER homeostasis and cell polarity.

The role of breastfeeding support in racial/ethnic disparities in breastfeeding practices.

BACKGROUND: Persistent racial/ethnic disparities in breastfeeding practices in the United States are well documented but the underlying causes remain unclear. While racial/ethnic disparities are often intertwined with socioeconomic disparities in breastfeeding, studies suggest that lack of breastfeeding support from family, health care organizations and workplaces may contribute to racial/ethnic disparities in breastfeeding rates. No studies have investigated the extent to which racial/ethnic disparities in breastfeeding practices can be explained by breastfeeding support. METHODS: We used survey data from participants of a federal nutrition assistance program in Los Angeles County, the most populous county in the United States, to examine causal mechanisms underlying racial/ethnic disparities in breastfeeding in five groups: Spanish-speaking Latina, English-speaking Latina, Non-Hispanic White (NHW), Non-Hispanic Black (NHB) and Non-Hispanic Asian (NHA). Applying causal mediation analysis, this study estimated the proportion of racial/ethnic differences in breastfeeding ('any' breastfeeding, i.e., partial or exclusive) rates at 6 months that could be explained by differential access to breastfeeding support from family, birth hospitals and workplaces. RESULTS: NHB and English-speaking Latina mothers were less likely, and Spanish-speaking Latina mothers more likely to breastfeed through 6 months than NHW mothers. Lack of breastfeeding support from family, hospitals and workplaces accounted for approximately 68% of the difference in any breastfeeding rates at 6 months between NHW and NHB mothers and 36% of the difference between NHW and English-speaking Latina mothers. CONCLUSION: These findings highlight the importance of improving support from family, hospitals and workplaces for breastfeeding mothers to reduce racial/ethnic disparities in breastfeeding.