Tag: pubmed

Genome Med. 2022 May 6;14(1):48. doi: 10.1186/s13073-022-01048-4.

ABSTRACT

BACKGROUND: Medical digital twins are computational disease models for drug discovery and treatment. Unresolved problems include how to organize and prioritize between disease-associated changes in digital twins, on cellulome- and genome-wide scales. We present a dynamic framework that can be used to model such changes and thereby prioritize upstream regulators (URs) for biomarker- and drug discovery.

METHODS: We started with seasonal allergic rhinitis (SAR) as a disease model, by analyses of in vitro allergen-stimulated peripheral blood mononuclear cells (PBMC) from SAR patients. Time-series a single-cell RNA-sequencing (scRNA-seq) data of these cells were used to construct multicellular network models (MNMs) at each time point of molecular interactions between cell types. We hypothesized that predicted molecular interactions between cell types in the MNMs could be traced to find an UR gene, at an early time point. We performed bioinformatic and functional studies of the MNMs to develop a scalable framework to prioritize UR genes. This framework was tested on a single-cell and bulk-profiling data from SAR and other inflammatory diseases.

RESULTS: Our scRNA-seq-based time-series MNMs of SAR showed thousands of differentially expressed genes (DEGs) across multiple cell types, which varied between time points. Instead of a single-UR gene in each MNM, we found multiple URs dispersed across the cell types. Thus, at each time point, the MNMs formed multi-directional networks. The absence of linear hierarchies and time-dependent variations in MNMs complicated the prioritization of URs. For example, the expression and functions of Th2 cytokines, which are approved drug targets in allergies, varied across cell types, and time points. Our analyses of bulk- and single-cell data from other inflammatory diseases also revealed multi-directional networks that showed stage-dependent variations. We therefore developed a quantitative approach to prioritize URs: we ranked the URs based on their predicted effects on downstream target cells. Experimental and bioinformatic analyses supported that this kind of ranking is a tractable approach for prioritizing URs.

CONCLUSIONS: We present a scalable framework for modeling dynamic changes in digital twins, on cellulome- and genome-wide scales, to prioritize UR genes for biomarker and drug discovery.

PMID:35513850 | DOI:10.1186/s13073-022-01048-4

Lab Anim Res. 2022 May 5;38(1):11. doi: 10.1186/s42826-022-00122-7.

ABSTRACT

BACKGROUND: Activating the immune system for therapeutic benefit has long been a goal in immunology, especially in cancer treatment, but the low immunogenicity of antitumor vaccines remains a limiting factor in the fight against malignant neoplasms. The increase in the immunogenicity of weak antigens using biodegradable polymers, such as chitosan, has been observed in the field of cancer immunotherapy. However, the effects of the vaccine using a combination of tumor cells and a thermoreversible delivery system based on chitosan in bladder cancer models, mainly using the intravesical route to stimulate the antitumor immune response, are unknown. We propose to evaluate the efficacy of a polymeric gel matrix (TPG) formed by poloxamer 407 and chitosan, associated with MB49 cells, as an intravesical antitumor vaccine using a C57BL/6 murine model of bladder urothelial carcinoma. The effectiveness of immunization was analyzed with the formation of three experimental groups: Control, TPG and TPG + MB49. In the vaccination phase, the TPG + MB49 group underwent a traumatic injury to the bladder wall with immediate intravesical instillation of the vaccine compound containing MB49 cells embedded in TPG. The TPG group was subjected to the same procedures using the compound containing the gel diluted in medium, and the control group using only the medium. After 21 days, the animals were challenged with tumor induction.

RESULTS: In vitro tests showed loss of viability and inability to proliferate after exposure to TPG. In vivo tests showed that animals previously immunized with TPG + MB49 had higher cumulative survival, as well as significantly lower bladder weight and size in contrast to the other two groups that did not show a statistically different tumor evolution. In addition, the splenocytes of these animals also showed a higher rate of antitumor cytotoxicity in relation to the TPG and control groups.

CONCLUSIONS: We can conclude that MB49 cells embedded in a polymeric thermoreversible gel matrix with chitosan used in the form of an intravesical vaccine are able to stimulate the immune response and affect the development of the bladder tumor in an orthotopic and syngeneic C57BL/6 murine model.

PMID:35513853 | DOI:10.1186/s42826-022-00122-7

World J Surg Oncol. 2022 May 6;20(1):144. doi: 10.1186/s12957-022-02606-1.

ABSTRACT

BACKGROUND: Pancreatic cancer is an aggressive malignancy, surgery being the only potentially curative treatment. The systemic inflammatory response is an important factor in the development of cancer. There is still controversy regarding its role in pancreatic cancer.

METHODS: Our study is a retrospective observational cohort study. We included patients diagnosed with pancreatic ductal adenocarcinoma (PDAC), who underwent surgical resection in our hospital, between January 2012 and December 2019. We gathered information from preoperative and postoperative blood tests. Neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), lymphocyte to monocyte ratio (LMR), prognostic nutritional index (PNI) and systemic immune-inflammation index (SII) were determined.

RESULTS: We included 312 patients. All the immune-inflammatory scores assessed significantly changed after the surgery. The impact on overall survival of these markers showed that only some of the postoperative scores predicted survival: high PLR had a negative prognostic impact, while high lymphocyte and PNI values had a positive effect on overall survival.

DISCUSSION: The circulating immune cells and their values integrated in the assessed prognostic scores suffer statistically significant changes after curative pancreatic surgery. Only the postoperative values of lymphocyte count, PLR, and PNI seem to influence the overall survival in PDAC.

TRIAL REGISTRATION: ClinicalTrials.gov-identifier NCT05025371 .

PMID:35513845 | DOI:10.1186/s12957-022-02606-1

BMC Public Health. 2022 May 5;22(1):897. doi: 10.1186/s12889-022-12989-1.

ABSTRACT

BACKGROUND: Policy debates over anti-poverty programs are often marked by pernicious stereotypes suggesting that direct cash transfers to people residing in poverty encourage health-risking behaviors such as smoking, drinking, and other substance use. Causal evidence on this issue is limited in the U.S. Given the prominent role of child allowances and other forms of cash assistance in the 2021 American Rescue Plan and proposed Build Back Better legislation, evidence on the extent to which a monthly unconditional cash gift changes substance use patterns among low-income mothers with infants warrants attention, particularly in the context of economic supports that can help improve early environments of children.

METHOD: We employ a multi-site, parallel-group, randomized control trial in which 1,000 low-income mothers in the U.S. with newborns were recruited from hospitals shortly after the infant’s birth and randomly assigned to receive either a substantial ($333) or a nominal ($20) monthly cash gift during the early years of the infant’s life. We estimate the effect of the unconditional cash transfer on self-report measures of maternal substance use (i.e., alcohol, cigarette, or opioid use) and household expenditures on alcohol and cigarettes after one year of cash gifts.

RESULTS: The cash gift difference of $313 per month had small and statistically nonsignificant impacts on group differences in maternal reports of substance use and household expenditures on alcohol or cigarettes. Effect sizes ranged between – 0.067 standard deviations and + 0.072 standard deviations. The estimated share of the $313 group difference spent on alcohol and tobacco was less than 1%.

CONCLUSIONS: Our randomized control trial of monthly cash gifts to mothers with newborn infants finds that a cash gift difference of $313 per month did not significantly change maternal use of alcohol, cigarettes, or opioids or household expenditures on alcohol or cigarettes. Although the structure of our cash gifts differs somewhat from that of a government-provided child allowance, our null effect findings suggest that unconditional cash transfers aimed at families living in poverty are unlikely to induce large changes in substance use and expenditures by recipients.

TRIAL REGISTRATION: Registered on Clinical Trials.gov NCT03593356 in July of 2018.

PMID:35513842 | DOI:10.1186/s12889-022-12989-1

BMC Res Notes. 2022 May 5;15(1):156. doi: 10.1186/s13104-022-06034-y.

ABSTRACT

OBJECTIVE: It has been shown that variable compared to fixed task prioritization during dual task practice more effectively improves motor (i.e., postural control) and cognitive (i.e., memory) performance in older adults. However, it is unclear whether this finding is also valid in young adults. Thus, the present study examined the effect of fixed (allocate equal priority on both tasks) versus variable (vary priority between both tasks) priority during short-term motor-cognitive dual task practice on single and dual task performance in healthy young adults (age range: 20-30 years).

RESULTS: During two days of practice, significant improvements of motor (i.e., balance task: reduced root mean square error; p < 001, η_p² = .72) and cognitive (i.e., arithmetic task: increased serial three subtractions; p < .001, η_p² = .78) task performance were observed and that was irrespective of group (“fixed priority” and “variable priority”). Further, the statistical analysis of post-practice single and dual task performance revealed no significant differences between groups, irrespective of task (i.e., motor or cognitive). This indicates that in young as opposed to old adults, single and dual task performance improvements are independent of task prioritization (i.e., fixed or variable priority) during short-term motor-cognitive dual task practice.

PMID:35513836 | DOI:10.1186/s13104-022-06034-y

BMC Health Serv Res. 2022 May 5;22(1):602. doi: 10.1186/s12913-022-07876-9.

ABSTRACT

BACKGROUND: Utilisation of continuum of maternal health care services is crucial for a healthy pregnancy and childbirth and plays an important role in attaining Universal Health Coverage (UHC) and Sustainable Development Goals (SDGs) related to maternal and child health. This paper aims to assess the percentage of dropouts across various stages of utilization of continuum of maternal health services (CMHS) in India and also investigates the factors hindering the utilization of these services.

METHODS: We used recent data from National Family Health Survey(NFHS) encompassing a total sample of 1,70,937 pregnant women for the period 2015-16. The percentage of women dropping out while seeking maternal health care is measured using descriptive statistics. While, the factors impeding the utilization of maternal health services is estimated using a Multinomial Logistic Regression Model, where dependent variable (CMHS) is defined as complete care, incomplete care and no care.

RESULTS: Only17% of pregnant women availed the utilisation of complete care and 83% either did not seek any care or dropped after seeking one or two services. For instance, it is found that 79% of women who registered for antenatal care services (ANC) did not avail the same adequately. An empirical investigation of determinants of inadequate utilization of CMHS revealed that factors like individual characteristics, for instance- access to media (RRR: 2.06) and mother’s education play (RRR: 3.61) a vital role in the uptake of CMHS. It is also found that the interaction between wealth index and place of residence plays a pivotal role in seeking complete care. Lastly, the results revealed that male participation (RRR: 2.69) and contacting multi-purpose worker (MPW) (RRR: 2.33) are also at play.

CONCLUSION: The study suggests that the major determinants of utilisation of CMHS are access to media, mother’s education, affordability barriers and male participation. Hence, policy recommendations should be oriented towards strengthening these dimensions and the utilisation of adequate ANC has to be considered as the need of the hour.

PMID:35513830 | DOI:10.1186/s12913-022-07876-9

BMC Vet Res. 2022 May 5;18(1):164. doi: 10.1186/s12917-022-03267-8.

ABSTRACT

BACKGROUND: Oral malodour is identified by pet owners as an unpleasant inconvenience, but they may not recognise this likely indicates underlying disease. The primary cause of oral malodour relates to the presence of bacteria in the oral cavity often associated with gingivitis and periodontitis. The purpose of this study was to determine the effect of feeding two oral care chews with different textural properties on oral malodour and the proportion of bacterial species involved in the production of volatile sulphur compounds (VSCs).

METHODS: Fourteen dogs (9 Petit Basset Griffon Vendéen (PBGV) and 5 Beagle dogs) participated in the randomised cross-over study for a total of 14 weeks. The cohort was divided into four groups with each exposed to a different intervention per week: chew A, chew B, tooth brushing control or a no intervention control. An induced malodour method was used to assess VSCs in breath samples using a portable gas chromatograph (OralChroma™). Microbiological samples (supragingival plaque and tongue coating scrapes) were analysed for VSC-producing bacteria using Oral Hydrogen Sulfide agar with lead acetate.

RESULTS: VSCs were detected in the dogs’ breath samples and levels of hydrogen sulphide and methyl mercaptan were found to be reduced following an intervention. Chew B significantly reduced the levels of both hydrogen sulphide (p < 0.001) and methyl mercaptan (p < 0.05) compared to no intervention. Reductions in methyl mercaptan were also observed for chew A and tooth brushing but these were not statistically significant. When compared to no intervention, all interventions significantly reduced the total bacterial load and VSC producing bacterial load in plaque (p < 0.001). For tongue samples, only chew B significantly reduced the total bacterial load and VSC-producing bacterial load (p < 0.001) compared to no intervention.

CONCLUSIONS: By inducing oral malodour and subsequently applying the one-time interventions, significant reductions in the levels of VSCs were observed. The use of oral care chews texturally designed to deliver a deep, all-round cleaning action can be particularly effective at managing oral malodour in dogs, likely through an enhanced ability to remove bacteria.

PMID:35513817 | DOI:10.1186/s12917-022-03267-8

BMC Psychiatry. 2022 May 5;22(1):322. doi: 10.1186/s12888-022-03966-4.

ABSTRACT

BACKGROUND: Common mental disorders such as depression, anxiety, and somatic symptoms are a major public health concern because it is prevalent and chronic, and its impact on physical health, psychological and economic consequences is very serious. Evidence on the prevalence and predictors of common mental disorders is very limited in Ethiopia. This study aims to determine the prevalence and associated factors with common mental disorders.

METHODS: A community-based cross-sectional study was conducted among 731 south Gondar zone residents recruited with a multistage sampling method. Data were collected by face-to-face interviews on socio-demographic, clinical, and psychosocial factors. Common mental disorders (CMD) were assessed using a self-reporting questionnaire (SRQ-20). A-List of Threatening Experiences and the Oslo social support instruments were used to identify the factors. We used bivariate and multivariable binary logistic regressions to identify factors associated with common mental disorders. Statistical significance was declared at P-value < 0.05.

RESULTS: The prevalence of common mental disorders over the last four weeks was found to be 29.7% with 95% of confidence interval (CI) (26.4-33.1). After adjusting possible confounders, female sex, [AOR = 2.47, 95% CI (1.68, 3.62)], poor social support [AOR = 2.34, 95% CI (1.50, 3.64)], family history of mental illness [AOR = 2.15, (1.32-3.51)], rural resident [AOR = 2.01, 95% CI (1.35, 3.01)], current use of khat [AOR = 1.69, 95% CI (1 0.07, 2.64)] current use of tobacco (AOR = 1.71, 95% CI (1.04-2.84) and unemployment [AOR = 1.762, 95% CI; 1.193, 2.602)] were significantly associated with common mental disorders.

CONCLUSION: The prevalence of common mental disorders was high, especially in Female sex, current substance use (khat chewing (leaves) and tobacco smoking), unemployment, rural residence, family history mental illness, and poor social support are the main determinants of common mental disorders. Early detection and appropriate intervention for common mental disorders in the community level should be promoted. Governmental strategies should be focused on implementing substance rehabilitation centers to treat Khat and tobacco might be helpful to minimize the burden of CMD in Ethiopia.

PMID:35513829 | DOI:10.1186/s12888-022-03966-4

BMC Musculoskelet Disord. 2022 May 5;23(1):422. doi: 10.1186/s12891-022-05371-0.

ABSTRACT

BACKGROUND: Suture anchors (SAs) made of human allogenic mineralized cortical bone matrix are among the newest developments in orthopaedic and trauma surgery. Biomechanical properties of an allogenic mineralized suture anchor (AMSA) are not investigated until now. The primary objective was the biomechanical investigation of AMSA and comparing it to a metallic suture anchor (MSA) and a bioabsorbable suture anchor (BSA) placed at the greater tuberosity of the humeral head of cadaver humeri. Additionally, we assessed the biomechanical properties of the SAs with bone microarchitecture parameters.

METHODS: First, bone microarchitecture of 12 fresh frozen human cadaver humeri from six donors was analyzed by high-resolution peripheral quantitative computed tomography. In total, 18 AMSAs, 9 MSAs, and 9 BSAs were implanted at a 60° angle. All three SA systems were systematically implanted alternating in three positions within the greater tuberosity (position 1: anterior, position 2: central, position 3: posterior) with a distance of 15 mm to each other. Biomechanical load to failure was measured in a uniaxial direction at 135°.

RESULTS: Mean age of all specimens was 53.6 ± 9.1 years. For all bone microarchitecture measurements, linear regression slope estimates were negative which implies decreasing values with increasing age of specimens. Positioning of all three SA systems at the greater tuberosity was equally distributed (p = 0.827). Mean load to failure rates were higher for AMSA compared to MSA and BSA without reaching statistical significance between the groups (p = 0.427). Anchor displacement was comparable for all three SA systems, while there were significant differences regarding failure mode between all three SA systems (p < 0.001). Maximum load to failure was reached in all cases for AMSA, in 44.4% for MSA, and in 55.6% for BSA. Suture tear was observed in 55.6% for MSA and in 22.2% for BSA. Anchor breakage was solely seen for BSA (22.2%). No correlations were observed between bone microarchitecture parameters and load to failure rates of all three suture anchor systems.

CONCLUSIONS: The AMSA showed promising biomechanical properties for initial fixation strength for RCR. Since reduced BMD is an important issue for patients with chronic rotator cuff lesions, the AMSA is an interesting alternative to MSA and BSA. Also, the AMSA could improve healing of the enthesis.

PMID:35513813 | DOI:10.1186/s12891-022-05371-0

BMC Health Serv Res. 2022 May 5;22(1):603. doi: 10.1186/s12913-022-07838-1.

ABSTRACT

BACKGROUND: A growing number of studies show that integrated health care provides comprehensive and continuous care to patients with hypertension or diabetes. However, there is still no consensus about the effect of integrated health care on patients with hypertension or diabetes. The objective of this study was to verify the effectiveness of integrated health care for patients with hypertension or diabetes by using a systematic review and meta-analysis.

METHODS: The study searched multiple English and Chinese electronic databases. The search period was from database inception to 31 October 2020. Systematic reviews and meta-analyses were conducted after assessing the risk of bias of each study.

RESULTS: Sixteen studies that involved 5231 patients were included in this study. The results of the systematic review revealed that systolic blood pressure (SBP), diastolic blood pressure (DBP), body mass index (BMI) and glycosylated haemoglobin (HbA1c) are commonly used indicators for patients with hypertension or diabetes. Individual models and group- and disease-specific models are the most commonly used models of integrated health care. All the studies were from high-income and middle-income countries. Meta-analysis showed that integrated health care significantly improved SBP, DBP and HbA1c but not BMI. A comparison of interventions lasting 6 and 12 months for diabetes was conducted, and HbA1c was decreased after 12 months. The changes in SBP and DBP were statistically significant after using group- and disease-specific model but not individual models. HbA1c was significantly improved after using group- and disease-specific models and individual models.

CONCLUSION: Integrated health care is a useful tool for disease management, and individual models and group- and disease-specific models are the most commonly used models in integrated health care. Group- and disease-specific models are more effective than individual models in the disease management of hypertension patients. The duration of intervention should be considered in the disease management of patients with diabetes, and interventions longer than 12 months are recommended. The income level may affect the model of integrated health care in selecting which disease to intervene, but this point still needs support from more studies.

PMID:35513809 | DOI:10.1186/s12913-022-07838-1