Multilayered Immunity by Tissue-Resident Lymphocytes in Cancer.

Lymphocytes spanning the entire innate-adaptive spectrum can stably reside in tissues and constitute an integral component of the local defense network against immunological challenges. In tight interactions with the epithelium and endothelium, tissue-resident lymphocytes sense antigens and alarmins elicited by infectious microbes and abiotic stresses at barrier sites and mount effector responses to restore tissue homeostasis. Of note, such a host cell-directed immune defense system has been recently demonstrated to surveil epithelial cell transformation and carcinoma development, as well as cancer cell metastasis at selected distant organs, and thus represents a primordial cancer immune defense module. Here we review how distinct lineages of tissue-resident innate lymphoid cells, innate-like T cells, and adaptive T cells participate in a form of multilayered cancer immunity in murine models and patients, and how their convergent effector programs may be targeted through both shared and private regulatory pathways for cancer immunotherapy.

Tissue-Resident T Cells and Other Resident Leukocytes.

Resident memory T (Trm) cells stably occupy tissues and cannot be sampled in superficial venous blood. Trm cells are heterogeneous but collectively constitute the most abundant memory T cell subset. Trm cells form an integral part of the immune sensing network, monitor for local perturbations in homeostasis throughout the body, participate in protection from infection and cancer, and likely promote autoimmunity, allergy, and inflammatory diseases and impede successful transplantation. Thus Trm cells are major candidates for therapeutic manipulation. Here we review CD8+ and CD4+ Trm ontogeny, maintenance, function, and distribution within lymphoid and nonlymphoid tissues and strategies for their study. We briefly discuss other resident leukocyte populations, including innate lymphoid cells, macrophages, natural killer and natural killer T cells, nonclassical T cells, and memory B cells. Lastly, we highlight major gaps in knowledge and propose ways in which a deeper understanding could result in new methods to prevent or treat diverse human diseases.

Tissue Determinants of Human NK Cell Development, Function, and Residence.

Immune responses in diverse tissue sites are critical for protective immunity and homeostasis. Here, we investigate how tissue localization regulates the development and function of human natural killer (NK) cells, innate lymphocytes important for anti-viral and tumor immunity. Integrating high-dimensional analysis of NK cells from blood, lymphoid organs, and mucosal tissue sites from 60 individuals, we identify tissue-specific patterns of NK cell subset distribution, maturation, and function maintained across age and between individuals. Mature and terminally differentiated NK cells with enhanced effector function predominate in blood, bone marrow, spleen, and lungs and exhibit shared transcriptional programs across sites. By contrast, precursor and immature NK cells with reduced effector capacity populate lymph nodes and intestines and exhibit tissue-resident signatures and site-specific adaptations. Together, our results reveal anatomic control of NK cell development and maintenance as tissue-resident populations, whereas mature, terminally differentiated subsets mediate immunosurveillance through diverse peripheral sites. VIDEO ABSTRACT.

Transcription activation is enhanced by multivalent interactions independent of phase separation.

Transcription factors (TFs) consist of a DNA-binding domain and an activation domain (AD) that are frequently considered to be independent and exchangeable modules. However, recent studies report that the physicochemical properties of the AD can control TF assembly at chromatin by driving phase separation into transcriptional condensates. Here, we dissected transcription activation by comparing different synthetic TFs at a reporter gene array with real-time single-cell fluorescence microscopy. In these experiments, binding site occupancy, residence time, and coactivator recruitment in relation to multivalent TF interactions were compared. While phase separation propensity and activation strength of the AD were linked, the actual formation of liquid-like TF droplets had a neutral or inhibitory effect on transcription activation. We conclude that multivalent AD-mediated interactions enhance the transcription activation capacity of a TF by increasing its residence time in the chromatin-bound state and facilitating the recruitment of coactivators independent of phase separation.

Cancer immunity by tissue-resident type 1 innate lymphoid cells and killer innate-like T cells.

Cancer progression can be restrained by tumor-infiltrating lymphocytes in a process termed cancer immunosurveillance. Based on how lymphocytes are activated and recruited to the tumor tissue, cancer immunity is either pre-wired, in which innate lymphocytes and innate-like T cells are directly recruited to and activated in tumors following their differentiation in primary lymphoid organs; or priming-dependent, in which conventional adaptive T cells are first primed by cognate antigens in secondary lymphoid organs before homing to and reactivated in tumors. While priming-dependent cancer immunity has been a focus of cancer immunology research for decades, in part due to historical preconception of cancer theory and tumor model choice as well as clinical success of conventional adaptive T cell-directed therapeutic programs, recent studies have revealed that pre-wired cancer immunity mediated by tissue-resident type 1 innate lymphoid cells (ILC1s) and killer innate-like T cells (ILTCKs) is an integral component of the cancer immunosurveillance process. Herein we review the distinct ontogenies and cancer-sensing mechanisms of ILC1s and ILTCKs in murine genetic cancer models as well as the conspicuously conserved responses in human malignancies. How ILC1s and ILTCKs may be targeted to broaden the scope of cancer immunotherapy beyond conventional adaptive T cells is also discussed.

Adrenomedullin 2/intermedin is a slow off-rate, long-acting endogenous agonist of the adrenomedullin2 G protein-coupled receptor.

Adrenomedullin 2/intermedin (AM2/IMD), adrenomedullin (AM), and calcitonin gene-related peptide (CGRP) have functions in the cardiovascular, lymphatic, and nervous systems by activating three heterodimeric receptors comprising the class B GPCR CLR and a RAMP1, -2, or -3 modulatory subunit. CGRP and AM prefer the RAMP1 and RAMP2/3 complexes, respectively, whereas AM2/IMD is thought to be relatively nonselective. Accordingly, AM2/IMD exhibits overlapping actions with CGRP and AM, so the rationale for this third agonist for the CLR-RAMP complexes is unclear. Here, we report that AM2/IMD is kinetically selective for CLR-RAMP3, known as the AM2R, and we define the structural basis for its distinct kinetics. In live cell biosensor assays, AM2/IMD-AM2R elicited longer-duration cAMP signaling than the other peptide-receptor combinations. AM2/IMD and AM bound the AM2R with similar equilibrium affinities, but AM2/IMD had a slower off-rate and longer receptor residence time, thus explaining its prolonged signaling capacity. Peptide and receptor chimeras and mutagenesis were used to map the regions responsible for the distinct binding and signaling kinetics to the AM2/IMD mid-region and the RAMP3 extracellular domain (ECD). Molecular dynamics simulations revealed how the former forms stable interactions at the CLR ECD-transmembrane domain interface and how the latter augments the CLR ECD binding pocket to anchor the AM2/IMD C terminus. These strong binding components only combine in the AM2R. Our findings uncover AM2/IMD-AM2R as a cognate pair with unique temporal features, reveal how AM2/IMD and RAMP3 collaborate to shape CLR signaling, and have significant implications for AM2/IMD biology.

A Segmented Regression Analysis of Household Income and Recurrent Falls Among Adults in a National Cohort Study.

Falls can have life-altering consequences for older adults, including extended recovery periods and compromised independence. Higher household income may mitigate the risk of falls by providing financial resources for mobility tools, remediation of environmental hazards, and needed supports, or it may buffer the impact of an initial fall on subsequent risk through improved assistance and care. Household income has not had a consistently observed association with falls in older adults; however, a segmented association may exist such that associations are attenuated above a certain income threshold. In this study, we utilized segmented negative binomial regression analysis to examine the association between household income and recurrent falls among 2,302 participants in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study recruited between 2003 and 2007. Income-fall association segments separated by changes in slope were considered. Model results indicated a 2-segment association between household income and recurrent falls in the past year. In the range below the breakpoint, household income was negatively associated with the rate of recurrent falls across all age groups examined; in a higher income range (from $20,000-$49,999 to ≥$150,000), the association was attenuated (weaker negative trend) or reversed (positive trend). These findings point to potential benefits of ensuring that incomes for lower-income adults exceed the threshold needed to confer a reduced risk of recurrent falls.

Regional invasion history and land use shape the prevalence of non-native species in local assemblages.

The ecological impact of non-native species arises from their establishment in local assemblages. However, the rates of non-native spread in new regions and their determinants have not been comprehensively studied. Here, we combined global databases documenting the occurrence of non-native species and residence of non-native birds, mammals, and vascular plants at regional and local scales to describe how the likelihood of non-native occurrence and their proportion in local assemblages relate with their residence time and levels of human usage in different ecosystems. Our findings reveal that local non-native occurrence generally increases with residence time. Colonization is most rapid in croplands and urban areas, while it is slower and variable in natural or semi-natural ecosystems. Notably, non-native occurrence continues to rise even 200 years after introduction, especially for birds and vascular plants, and in other land-use types rather than croplands and urban areas. The impact of residence time on non-native proportions is significant only for mammals. We conclude that the continental exchange of biotas requires considerable time for effects to manifest at the local scale across taxa and land-use types. The unpredictability of future impacts, implied by the slow spread of non-native species, strengthens the call for stronger regulations on the exchange of non-native species to reduce the long-lasting invasion debt looming on ecosystems' future.

Climate warming accelerates carbon release from foliar litter-A global synthesis.

With over one-third of terrestrial net primary productivity transferring to the litter layer annually, the carbon release from litter serves as a crucial valve in atmospheric carbon dioxide concentrations. However, few quantitative global projections of litter carbon release rate in response to climate change exist. Here, we combined a global foliar litter carbon release dataset (8973 samples) to generate spatially explicitly estimates of the response of their residence time (τ) to climate change. Results show a global mean litter carbon release rate ( k $$ k $$ ) of 0.69 year-1 (ranging from 0.09-5.6 year-1). Under future climate scenarios, global mean τ is projected to decrease by a mean of 2.7% (SSP 1-2.6) and 5.9% (SSP 5-8.5) during 2071-2100 period. Locally, the alleviation of temperature and moisture restrictions corresponded to obvious decreases in τ in cold and arid regions, respectively. In contract, τ in tropical humid broadleaf forests increased by 4.6% under SSP 5-8.5. Our findings highlight the vegetation type as a powerful proxy for explaining global patterns in foliar litter carbon release rates and the role of climate conditions in predicting responses of carbon release to climate change. Our observation-based estimates could refine carbon cycle parameterization, improving projections of carbon cycle-climate feedbacks.

Anoxia begets anoxia: A positive feedback to the deoxygenation of temperate lakes.

Declining oxygen concentrations in the deep waters of lakes worldwide pose a pressing environmental and societal challenge. Existing theory suggests that low deep-water dissolved oxygen (DO) concentrations could trigger a positive feedback through which anoxia (i.e., very low DO) during a given summer begets increasingly severe occurrences of anoxia in following summers. Specifically, anoxic conditions can promote nutrient release from sediments, thereby stimulating phytoplankton growth, and subsequent phytoplankton decomposition can fuel heterotrophic respiration, resulting in increased spatial extent and duration of anoxia. However, while the individual relationships in this feedback are well established, to our knowledge, there has not been a systematic analysis within or across lakes that simultaneously demonstrates all of the mechanisms necessary to produce a positive feedback that reinforces anoxia. Here, we compiled data from 656 widespread temperate lakes and reservoirs to analyze the proposed anoxia begets anoxia feedback. Lakes in the dataset span a broad range of surface area (1-126,909 ha), maximum depth (6-370 m), and morphometry, with a median time-series duration of 30 years at each lake. Using linear mixed models, we found support for each of the positive feedback relationships between anoxia, phosphorus concentrations, chlorophyll a concentrations, and oxygen demand across the 656-lake dataset. Likewise, we found further support for these relationships by analyzing time-series data from individual lakes. Our results indicate that the strength of these feedback relationships may vary with lake-specific characteristics: For example, we found that surface phosphorus concentrations were more positively associated with chlorophyll a in high-phosphorus lakes, and oxygen demand had a stronger influence on the extent of anoxia in deep lakes. Taken together, these results support the existence of a positive feedback that could magnify the effects of climate change and other anthropogenic pressures driving the development of anoxia in lakes around the world.

Evaluation of 4D Flow MRI-Derived Relative Residence Time as a Marker for Cirrhosis Associated Portal Vein Thrombosis.

BACKGROUND: Portal vein thrombosis (PVT) is thought to arise from stagnant blood flow, yet conclusive evidence is lacking. Relative residence time (RRT) assessed using 4D Flow MRI may offer insight into portal flow stagnation. PURPOSE: To explore the relationship between RRT values and the presence of PVT in cirrhotic participants. STUDY TYPE: Prospective. POPULATION: Forty-eight participants with liver cirrhosis (27 males, median age 67 years [IQR: 57-73]) and 20 healthy control participants (12 males, median age 45 years [IQR: 40-54]). FIELD STRENGTH/SEQUENCE: 3 T/4D Flow MRI. ASSESSMENT: Laboratory (liver and kidney function test results and platelet count) and clinical data (presence of tumors and other imaging findings), and portal hemodynamics derived from 4D Flow MRI (spatiotemporally averaged RRT [RRT-mean], flow velocity, and flow rate) were analyzed. STATISTICAL TESTS: We used multivariable logistic regression, adjusted by selected covariates through the Lasso method, to explore whether RRT-mean is an independent risk factor for PVT. The area under the ROC curve (AUC) was also calculated to assess the model's discriminative ability. P < 0.05 indicated statistical significance. RESULTS: The liver cirrhosis group consisted of 16 participants with PVT and 32 without PVT. Higher RRT-mean values (odds ratio [OR] 11.4 [95% CI: 2.19, 118]) and lower platelet count (OR 0.98 per 1000 µL [95% CI: 0.96, 0.99]) were independent risk factors for PVT. The incorporation of RRT-mean (AUC, 0.77) alongside platelet count (AUC, 0.75) resulted in an AUC of 0.84. When including healthy control participants, RRT-mean had an adjusted OR of 12.4 and the AUC of the combined model (RRT-mean and platelet count) was 0.90. DATA CONCLUSION: Prolonged RRT values and low platelet count were significantly associated with the presence of PVT in cirrhotic participants. RRT values derived from 4D Flow MRI may have potential clinical relevance in the management of PVT. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Residence time distribution in continuous virus filtration.

Regulatory authorities recommend using residence time distribution (RTD) to address material traceability in continuous manufacturing. Continuous virus filtration is an essential but poorly understood step in biologics manufacturing in respect to fluid dynamics and scale-up. Here we describe a model that considers nonideal mixing and film resistance for RTD prediction in continuous virus filtration, and its experimental validation using the inert tracer NaNO3. The model was successfully calibrated through pulse injection experiments, yielding good agreement between model prediction and experiment ( R 2 > ${R}^{2}\gt $ 0.90). The model enabled the prediction of RTD with variations-for example, in injection volumes, flow rates, tracer concentrations, and filter surface areas-and was validated using stepwise experiments and combined stepwise and pulse injection experiments. All validation experiments achieved R 2 > ${R}^{2}\gt $ 0.97. Notably, if the process includes a porous material-such as a porous chromatography material, ultrafilter, or virus filter-it must be considered whether the molecule size affects the RTD, as tracers with different sizes may penetrate the pore space differently. Calibration of the model with NaNO3 enabled extrapolation to RTD of recombinant antibodies, which will promote significant savings in antibody consumption. This RTD model is ready for further application in end-to-end integrated continuous downstream processes, such as addressing material traceability during continuous virus filtration processes.

Carry-over effects of seasonal migration on reproductive success through breeding site retention in a partially migratory bird.

Understanding the maintenance and dynamics of phenotypic polymorphisms requires unpicking key ecological mechanisms shaping the fitness costs and benefits of expressing alternative phenotypes, generating selection. Seasonal migration versus year-round residence expressed in partially migratory populations represents one common polymorphism that can experience strong selection through differential reproductive success. Yet, key hypothesised pathways that could generate such selection remain to be empirically tested. One hypothesis is that migratory tactics affect subsequent reproductive success through carry-over effects on breeding site retention and resulting breeding dispersal. By remaining in breeding areas all year round, residents could retain their preferred breeding site between years, and consequently have higher reproductive success. Conversely, migrants that escape harsh non-breeding season conditions could return in better condition, with high resource holding potential, and outcompete residents to retain their site. Such effects could further depend on migration timing and vary between years. Yet, such pathways have not been quantified, precluding empirical parameterisation of partial migration theory. We used 4 years of breeding and non-breeding season data from partially migratory European shags (Gulosus aristotelis) to test whether the three most frequent migratory tactics in this population (full resident, early migrant departing soon after breeding, and late migrant departing in late autumn) differed in their breeding site retention; whether site retention predicted reproductive success; and hence whether effects of migratory tactic on reproductive success were explicable through site retention. Overall, residents were much more likely to retain their breeding site between years than both early and late migrants, and site retention was associated with increased reproductive success. Yet, these effects varied somewhat among years: late migrants were always least likely to retain their site but had variable relative reproductive success. Path analyses revealed that effects of migratory tactic on reproductive success were only partly attributable to breeding site retention. These results indicate that multiple mechanisms underlie reproductive selection on migratory tactics, potentially contributing to maintaining behavioural polymorphisms. Yet, the clear associations between migratory tactics and local breeding dispersal reveal that these movements can be strongly interlinked across seasons, shaping overall spatioseasonal dynamics in partially migratory systems.

Examining U.S. disparities in smoking among rural versus urban women of reproductive age: 2002-2019.

OBJECTIVE: This study is part of a programmatic investigation of rural disparities in cigarette smoking examining disparities in smoking prevalence and for the first-time quit ratios among adult women of reproductive age (18-44 years), a highly vulnerable population due to risk for multigenerational adverse effects. METHODS: Data came from 18 years (2002-2019) of the U.S. National Survey on Drug Use and Health (NSDUH) among women (n = 280,626) categorized by rural-urban residence, pregnancy status, using weighted logistic regression models testing time trends and controlling for well-established sociodemographic predictors of smoking (race/ethnicity, education, income). Concerns regarding changes in survey methods used before 2002 and after 2019 precluded inclusion of earlier and more recent survey years in the present study. RESULTS: Overall smoking prevalence across years was greater in rural than urban residents (adjusted odds ratio [AOR] = 1.11; 95%CI, 1.07-1.15; P < .001) including those not-pregnant (AOR = 1.10; 1.07-1.14; P < .001) and pregnant (AOR = 1.29; 1.09-1.52; P < .001). Overall quit ratios across years were lower in rural than urban residents (AOR = 0.93; 0.87-0.99; P < .001) including those not-pregnant (AOR = 0.93; 0.88-1.00, P = .035) and pregnant (AOR = 0.78; 0.62-0.99; P = .039). Interactions of rural versus urban residence with study years for prevalence and quit ratios overall and by pregnancy status are detailed in the main text. CONCLUSIONS: These results support a longstanding and robust rural disparity in smoking prevalence among women of reproductive age including those currently pregnant and provides novel evidence that differences in smoking cessation contribute to this disparity further underscoring a need for greater access to evidence-based tobacco control and regulatory interventions in rural regions.

Erosion of the Capital City Advantage in Child Survival and Reproductive, Maternal, Newborn, and Child Health Intervention Coverage in Sub-Saharan Africa.

The place of residence is a major determinant of RMNCH outcomes, with rural areas often lagging in sub-Saharan Africa. This long-held pattern may be changing given differential progress across areas and increasing urbanization. We assessed inequalities in child mortality and RMNCH coverage across capital cities and other urban and rural areas. We analyzed mortality data from 163 DHS and MICS in 39 countries with the most recent survey conducted between 1990 and 2020 and RMNCH coverage data from 39 countries. We assessed inequality trends in neonatal and under-five mortality and in RMNCH coverage using multilevel linear regression models. Under-five mortality rates and RMNCH service coverage inequalities by place of residence have reduced substantially in sub-Saharan Africa, with rural areas experiencing faster progress than other areas. The absolute gap in child mortality between rural areas and capital cities and that between rural and other urban areas reduced respectively from 41 and 26 deaths per 1000 live births in 2000 to 23 and 15 by 2015. Capital cities are losing their primacy in child survival and RMNCH coverage over other urban areas and rural areas, especially in Eastern Africa where under-five mortality gap between capital cities and rural areas closed almost completely by 2015. While child mortality and RMNCH coverage inequalities are closing rapidly by place of residence, slower trends in capital cities and urban areas suggest gradual erosion of capital city and urban health advantage. Monitoring child mortality and RMNCH coverage trends in urban areas, especially among the urban poor, and addressing factors of within urban inequalities are urgently needed.

Geographical Variation In Medication and Health Resource Use In Multiple Sclerosis.

BACKGROUND: Understanding disease-modifying therapy (DMT) use and healthcare resource utilization by different geographical areas among people living with multiple sclerosis (pwMS) may identify care gaps that can be used to inform policies and practice to ensure equitable care. METHODS: Administrative data was used to identify pwMS on April 1, 2017 (index date) in Alberta. DMT use and healthcare resource utilization were compared between those who resided in various geographical areas over a 2-year post-index period; simple logistic regression was applied. RESULTS: Among the cohort (n = 12,338), a higher proportion of pwMS who resided in urban areas (versus rural) received ≥ 1 DMT dispensation (32.3% versus 27.4%), had a neurologist (67.7% versus 63.9%), non-neurologist specialist (88.3% versus 82.9%), ambulatory care visit (87.4% versus 85.3%), and MS tertiary clinic visit (59.2% versus 51.7%), and a lower proportion had an emergency department (ED) visit (46.3% versus 62.4%), and hospitalization (20.4% versus 23.0%). Across the provincial health zones, there were variations in DMT selection, and a higher proportion of pwMS who resided in the Calgary health zone, where care is managed by MS tertiary clinic neurologists, had an outpatient visit to a neurologist or MS tertiary clinic versus those who resided in other zones where delivery of MS-related care is more varied. CONCLUSIONS: Urban/rural inequalities in DMT use and healthcare resource utilization appear to exist among pwMS in Alberta. Findings suggest the exploration of barriers with consequent strategies to increase access to DMTs and provide timely outpatient MS care management, particularly for those pwMS residing in rural areas.

Epidemiology of congenital polydactyly and syndactyly in Hunan Province, China.

OBJECTIVE: To describe the prevalence and epidemiology of congenital polydactyly and syndactyly in Hunan Province, China, 2016-2020. METHODS: Data were obtained from the Birth Defects Surveillance System in Hunan Province, China, 2016-2020. Prevalence of birth defects (polydactyly or syndactyly) is the number of cases per 1000 births (unit: ‰). Prevalence and 95% confidence intervals (CI) were calculated by the log-binomial method. Chi-square trend tests (χ2trend) were used to determine trends in prevalence by year. Crude odds ratios (ORs) were calculated to examine the association of each demographic characteristic with polydactyly and syndactyly. RESULTS: Our study included 847,755 births, and 14,459 birth defects were identified, including 1,888 polydactyly and 626 syndactyly cases, accounting for 13.06% and 4.33% of birth defects, respectively. The prevalences of total birth defects, polydactyly, and syndactyly were 17.06‰ (95%CI: 16.78-17.33), 2.23‰ (95%CI: 2.13-2.33), and 0.74‰ (95%CI: 0.68-0.80), respectively. Most polydactyly (96.77%) and syndactyly (95.69%) were diagnosed postnatally (within 7 days). From 2016 to 2020, the prevalences of polydactyly were 1.94‰, 2.07‰, 2.20‰, 2.54‰, and 2.48‰, respectively, showing an upward trend (χ2trend = 19.48, P < 0.01); The prevalences of syndactyly were 0.62‰, 0.66‰, 0.77‰, 0.81‰, and 0.89‰, respectively, showing an upward trend (χ2trend = 10.81, P = 0.03). Hand polydactyly (2.26‰ vs. 1.33‰, OR = 1.69, 95%CI: 1.52-1.87) and hand syndactyly (0.43‰ vs. 0.28‰, OR = 1.42, 95%CI: 1.14-1.76) were more common in males than females. Polydactyly (2.67‰ vs. 1.93‰, OR = 1.38, 95%CI: 1.26-1.51) and syndactyly (0.91‰ vs. 0.62‰, OR = 1.47, 95%CI: 1.26-1.72) were more common in urban areas than in rural areas. Compared to maternal age 25-29, hand polydactyly was more common in maternal age < 20 (2.48‰ vs. 1.74‰, OR = 1.43, 95%CI: 1.01-2.02) or ≥ 35 (2.25‰ vs. 1.74‰, OR = 1.30, 95%CI: 1.12-1.50). CONCLUSION: In summary, we have described the prevalence and epidemiology of polydactyly and syndactyly from hospital-based surveillance in Hunan Province, China, 2016-2020. Our findings make some original contributions to the field, which may be valuable for future research.

Activities of daily living limitations and the use of physical examination among older adults with informal care in China: do gender and residence make differences?

BACKGROUND: This study investigated the relationship between activities of daily living (ADL) limitations and the use of physical examination among older adults receiving informal care, and to further examine whether this relationship varies by gender and urban-rural areas. METHODS: The data in this study were obtained from the sixth Health Service of Shandong province, China. In total, 8,358 older adults aged 60 years or older who received informal care were included in the analysis. Binary logistic regression models were conducted to explore the association between ADL limitations and the use of physical examination and examine the differences between gender and urban-rural areas. RESULTS: The prevalence of limitations in ADL and physical examination utilization rate among older adults receiving informal care in Shandong Province were 14.12% and 72.31%, respectively. After adjusting for confounders, ADL limitations were negatively correlated with the utilization of physical examination services among older adults receiving informal care (OR = 0.74, 95% CI: 0.64, 0.87, P < 0.001), and there were gender and rural-urban differences. The association between ADL limitations and the use of physical examination was statistically significant in older women receiving informal care (OR = 0.65, 95% CI: 0.53, 0.80, P < 0.001). And only among urban older adults receiving informal care, those with ADL limitations had lower utilization of physical examination services than participants without ADL limitations (OR = 0.59, 95% CI: 0.47, 0.74, P < 0.001). CONCLUSIONS: Our study suggested that the relationship between ADL limitations and the use of physical examination among older adults receiving informal care differed by gender and urban-rural areas in Shandong, China. These findings implied that the government should provide more health resources and personalized physical examination service programs, especially to meet the differential needs of women and urban old adults receiving informal care, to contribute to the implementation of healthy aging strategies.

Differences in nutritional status and level of physical activity among adolescents living in urban and rural areas of Montenegro - national study.

BACKGROUND: Nutritional status and physical activity are important factors for adolescent health. These factors may vary by the place of residence. This study aims to assess the nutritional status and physical activity levels, as well as their variations by the place of residence. METHODS: The sample consisted of 1503 adolescents (46.3% male; 53.7% female), with a mean age of 15.7 ± 0.7 years. Nutritional status was assessed using Body Mass Index (BMI), Waist-to-Height Ratio (WHtR), and Body Fat Percentage (BF). Physical activity levels were assessed using the PAQ-C questionnaire. Differences in nutritional status among adolescents living in urban and rural areas were analyzed using Chi-square test (p ≤ 0.05), while differences in physical activity levels were analyzed using an independent samples t-test (p ≤ 0.05). RESULTS: In terms of BMI, 14.7% of males were overweight and 10.1% were obese, while 12% of female adolescents were overweight and 3.1% were obese. There were no differences in nutritional status among adolescents living in urban and rural areas (BMI, WHtR, BF). Male adolescents in rural areas had significantly higher physical activity levels compared to urban areas (p = 0.032). They showed higher activity scores during a spare time (p = 0.002), physical education classes (p = 0.002), little breaks (p = 0.007), and lunchtime (p = 0.034). Female adolescents showed significance only in spare time activity (p = 0.020). CONCLUSION: The differences in nutritional status among adolescents living in urban and rural areas were not found. However, male adolescents living in urban areas showed lower physical activity levels than their rural counterparts. Strategies should be implemented to promote physical activity among adolescents in urban areas, and attention should be given to the further urbanization process to create improved conditions for engaging in physical activity.

Socioeconomic and residence-based inequalities in adolescent fertility in 39 African countries.

INTRODUCTION: Despite the advancement in sexual and reproductive healthcare services and several public health measures aimed at controlling fertility rates, countries in sub-Saharan Africa (SSA) still experience higher adolescent fertility rates than other low-and middle-income countries. This study examined the disparities in adolescent fertility in 39 countries in SSA, focusing on socioeconomic and residence-based dimensions. METHODS: This study involved a secondary analysis of data obtained from 39 recent Demographic and Health Surveys conducted in SSA. The measures of difference (D), ratio (R), population attributable fraction (PAF), and population attributable risk (PAR) were estimated using the Health Equity Assessment Tool (HEAT) software version 3.1 developed by the World Health Organization. The measures: D, R, PAF, and PAR were used to examine the inequalities in adolescent fertility across the socioeconomic and residence-based dimensions. RESULTS: Out of the 39 countries included in the study, Guinea (D=27.70), Niger (D=27.50), Nigeria (D=23.90), and Côte d'Ivoire (D=23.60) exhibited the most significant residence-based inequalities in the rate of adolescent fertility, with the higher rate observed among adolescents in rural areas. Rwanda was the sole country that showed a slight inclination towards rural inequality in terms of the rate of adolescent fertility, with a value of D = -0.80. The burden of adolescent fertility was disproportionately higher among young women with low economic status across all the countries, exacerbating wealth-based inequities. The countries with the largest absolute discrepancies were Nigeria (D=44.70), Madagascar (D=41.10), Guinea (D=41.00), and Cameroon (D=40.20). We found significant disparities in educational attainment contributing to unequal inequalities in adolescent fertility, particularly among young women who lack access to formal education. Countries such as Madagascar (D=59.50), Chad (D=55.30), Cameroon (D=54.60), and Zimbabwe (D=50.30) had the most significant absolute disparities. CONCLUSION: This study revealed that young women residing in rural areas, those in households with low economic status and those with limited educational opportunities experience a disproportionately high burden of adolescent fertility across the 39 countries in SSA. The current findings offer valuable information to governmental entities at all levels regarding the need to ensure the provision of equitable, accessible, and dependable sexual and reproductive health services to the populace, particularly for young women. Therefore, the various stakeholders need to enhance the effectiveness of health policies and legislation pertaining to adolescent women living in rural areas, those from economically disadvantaged households, and those with limited or no access to formal education. Such interventions could potentially reduce adolescent fertility rates and mitigate the adverse maternal and child outcomes associated with high adolescent fertility in SSA.

Adolescent fertility is a major health problem for many developing countries, especially those in sub-Saharan Africa (SSA). Although several sexual and reproductive health initiatives have been introduced in these countries, the number of births among adolescents continues to be high. The present study looked at the socioeconomic and geographical differences in adolescent fertility across 39 countries in SSA using data from the Demographic and Health Surveys embedded into the World Health Organization's Health Equity Assessment Toolkit (WHO HEAT) software. The study found that in countries like Guinea, Niger, Nigeria, and Côte d'Ivoire, the rates of adolescent fertility varied a lot, with higher rates in rural areas. Generally, poorer young women were more likely to have babies, which made the gap between the rich and the poor even wider. Nigeria, Madagascar, Guinea, and Cameroon had the biggest differences. Education also played a role. In countries like Madagascar, Chad, Cameroon, and Zimbabwe, young women who did not go to school (had no education) were more likely to have children as teenagers.  The study showed that in all 39 countries, young women living in rural areas, those who were poorer and those who did not go to school (had no education) faced a bigger problem with adolescent fertility. The study suggests that if people who make health policies pay more attention to teenage girls in the rural areas, those who are poor and do not have much education, they could make a significant difference in reducing adolescent fertility.