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Tissue catabolism and donor-specific dexamethasone response in a human osteochondral model of post-traumatic osteoarthritis

Arthritis Res Ther. 2022 Jun 10;24(1):137. doi: 10.1186/s13075-022-02828-4.

ABSTRACT

BACKGROUND: Post-traumatic osteoarthritis (PTOA) does not currently have clinical prognostic biomarkers or disease-modifying drugs, though promising candidates such as dexamethasone (Dex) exist. Many challenges in studying and treating this disease stem from tissue interactions that complicate understanding of drug effects. We present an ex vivo human osteochondral model of PTOA to investigate disease effects on cartilage and bone homeostasis and discover biomarkers for disease progression and drug efficacy.

METHODS: Human osteochondral explants were harvested from normal (Collins grade 0-1) ankle talocrural joints of human donors (2 female, 5 male, ages 23-70). After pre-equilibration, osteochondral explants were treated with a single-impact mechanical injury and TNF-α, IL-6, and sIL-6R ± 100 nM Dex for 21 days and media collected every 2-3 days. Chondrocyte viability, tissue DNA content, and glycosaminoglycan (sGAG) percent loss to the media were assayed and compared to untreated controls using a linear mixed effects model. Mass spectrometry analysis was performed for both cartilage tissue and pooled culture medium, and the statistical significance of protein abundance changes was determined with the R package limma and empirical Bayes statistics. Partial least squares regression analyses of sGAG loss and Dex attenuation of sGAG loss against proteomic data were performed.

RESULTS: Injury and cytokine treatment caused an increase in the release of matrix components, proteases, pro-inflammatory factors, and intracellular proteins, while tissue lost intracellular metabolic proteins, which was mitigated with the addition of Dex. Dex maintained chondrocyte viability and reduced sGAG loss caused by injury and cytokine treatment by 2/3 overall, with donor-specific differences in the sGAG attenuation effect. Biomarkers of bone metabolism had mixed effects, and collagen II synthesis was suppressed with both disease and Dex treatment by 2- to 5-fold. Semitryptic peptides associated with increased sGAG loss were identified. Pro-inflammatory humoral proteins and apolipoproteins were associated with lower Dex responses.

CONCLUSIONS: Catabolic effects on cartilage tissue caused by injury and cytokine treatment were reduced with the addition of Dex in this osteochondral PTOA model. This study presents potential peptide biomarkers of early PTOA progression and Dex efficacy that can help identify and treat patients at risk of PTOA.

PMID:35689293 | DOI:10.1186/s13075-022-02828-4

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Immediate and six-week effects of wearing a knee sleeve following anterior cruciate ligament reconstruction on knee kinematics and kinetics: a cross-over laboratory and randomised clinical trial

BMC Musculoskelet Disord. 2022 Jun 10;23(1):560. doi: 10.1186/s12891-022-05488-2.

ABSTRACT

BACKGROUND: Elastic knee sleeves are often worn following anterior cruciate ligament reconstruction (ACLR) but their effects on movement patterns are unclear.

AIM: To determine the immediate and six-week effects of wearing a knee sleeve on biomechanics of the knee during a step-down hop task.

METHODS: Using a cross-over design, we estimated sagittal plane knee kinematics and kinetics and stance duration during a step-down hop for 31 participants (age 26.0 [SD 6.6] years, 15 women) after ACLR (median 16 months post-surgery) with and without wearing a knee sleeve. In a subsequent randomised clinical trial, participants in the ‘Sleeve Group’ (n = 9) then wore the sleeve for 6 weeks at least 1 h daily, while a ‘Control Group’ (n = 9) did not wear the sleeve. We used statistical parametric mapping to compare (1) knee flexion/extension angle and external flexion/extension moment trajectories between three conditions at baseline (uninjured side, unsleeved injured side and sleeved injured side); (2) within-participant changes for knee flexion angles and external flexion/extension moment trajectories from baseline to follow-up between groups. We compared discrete flexion angles and moments, and stance duration between conditions and between groups.

RESULTS: Without sleeves, knee flexion was lower for the injured than the uninjured sides during mid-stance phase. When wearing the sleeve on the injured side, knee flexion increased during the loading phase of the stance phase. Discrete initial and peak knee flexion angles increased by (mean difference, 95% CIs) 2.7° (1.3, 4.1) and 3.0° (1.2, 4.9), respectively, when wearing the knee sleeve. Knee external flexion moments for the unsleeved injured sides were lower than the uninjured sides for 80% of stance phase, with no change when sleeved. The groups differenced for within-group changes in knee flexion trajectories at follow-up. Knee flexion angles increased for the Control group only. Stance duration decreased by 22% for the Sleeve group from baseline to follow-up (-89 ms; -153, -24) but not for the Controls.

CONCLUSIONS: Application of knee sleeves following ACLR is associated with improved knee flexion angles during hop landing training. Longer term (daily) knee sleeve application may help improve hop stance duration, potentially indicating improved hop performance.

TRIAL REGISTRATION: The trial was prospectively registered with the Australia New Zealand Clinical Trials Registry No: ACTRN12618001083280, 28/06/2018. ANZCTR.

PMID:35689284 | DOI:10.1186/s12891-022-05488-2

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Biomechanical comparison of the femoral neck system versus InterTan nail and three cannulated screws for unstable Pauwels type III femoral neck fracture

Biomed Eng Online. 2022 Jun 10;21(1):34. doi: 10.1186/s12938-022-01006-6.

ABSTRACT

BACKGROUND: There are a variety of internal fixation methods for unstable femoral neck fractures (FNFs), but the best method is still unclear. Femoral neck system (FNS) is a dynamic angular stabilization system with cross screws, and is a new internal fixation implant designed for minimally invasive fixation of FNFs. In this study, we conducted a biomechanical comparison of FNS, InterTan nail and three cannulated screws for the treatment of Pauwels III FNFs and investigate the biomechanical properties of FNS.

METHODS: A total of 18 left artificial femurs were selected and randomly divide into Group A (fixation with FNS), Group B (fixation with InterTan nail) and Group C (fixation with three cannulated screws), with 6 specimens in each group. After creating Pauwels type III FNF models, the specimens in each were tested with non-destructive quasi-static tests, including torsion, A-P bending and axial compression tests. The average slope of the linear load-deformation curve obtained from quasi-static tests defines the initial torsional stiffness, A-P bending stiffness, and axial compression stiffness. After cyclic loading test was applied, the overall deformation of models and local deformation of implant holes in each group were assessed. The overall deformation was estimated as the displacement recorded by the software of the mechanical testing apparatus. Local deformation was defined as interfragmental displacement. Data were analyzed by one-way analysis of variance (ANOVA) followed by Bonferroni post hoc test using the SPSS software (version 24.0, IBM, New York, NY, USA). Correlation analysis was performed using Pearson’s correlation analysis.

RESULTS: Group B exhibited significantly higher axial stiffness and A-P bending stiffness than the other two groups (P < 0.01), while Group A had significantly higher axial stiffness and A-P bending stiffness than Group C (P < 0.01). Groups A and B exhibited significantly higher torsional stiffness than Group C (P < 0.01), no statistical significance was observed between Groups A and B (P > 0.05). Group B exhibited significantly lower overall and local deformations than the other two groups (P < 0.01), while Group A had significantly lower overall and local deformations than Group C (P < 0.01). Correlation analysis revealed positive correlation between axial stiffness and A-P bending stiffness (r = 0.925, P < 0.01), torsional stiffness (r = 0.727, P < 0.01), between torsional stiffness and A-P bending stiffness; negative correlation between overall, local deformations and axial stiffness (r = – 0.889, – 0.901, respectively, both P < 0.01), and positive correlation between the two deformations (r = – 0.978, P < 0.01).

CONCLUSION: For fixation of unstable FNFs, InterTan nail showed the highest axial stiffness and A-P bending stiffness, followed by FNS, and then three cannulated screws. Torsional stiffness of FNS was comparable to that of the InterTan nail. FNS, as a novel minimally invasive implant, can create good mechanical environment for the healing of unstable FNFs. Clinical studies are needed to confirm the potential advantages of FNS observed in this biomechanical study.

PMID:35689282 | DOI:10.1186/s12938-022-01006-6

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Burden and pattern of acute diarrhea in Thai children under 5 years of age: a 5-year descriptive analysis based on Thailand National Health Coverage (NHC) data

BMC Public Health. 2022 Jun 10;22(1):1161. doi: 10.1186/s12889-022-13598-8.

ABSTRACT

BACKGROUND: The incidence of acute diarrhea in Thai children under five years of age has increased over the last three decades. Even though mortality has significantly declined, the burden and cost of medical treatment are still high. Our objectives are to describe the burden and pattern of acute diarrhea cases that required admissions by Thai children under five years of age from 2015 to 2019.

METHODS: Data regarding the admission of acute diarrhea cases of Thai children with Thailand National Health Coverage (NHC) under five years of age from 2015 to 2019, recorded as International Statistical Classification of Diseases and Related Health Problems, tenth Revision, Thai Modification (ICD-10-TM), were analyzed.

RESULTS: The incidence trend of yearly acute diarrhea in children 0-5 years of age slightly increased from 33.36 cases per 1,000 population in 2010 to an average of 33.79 cases per 1,000 population/ year from 2015 to 2019 or approximately 0.43 cases per 1,000 population over the last decade while diarrhea-related mortality had a low, constant rate of 0.71 to 1.16 per 100,000 population per year. Two thirds of the mortality rate was observed in children under 1 year of age or 4.1 cases per 100,000 person-years in 5-year period (P < 0.01). The high cost of performing the medical treatment of approximately four hundred million baht per year. Seasonal variations demonstrated consistency with similar patterns during the cold and rainy seasons throughout the 5-year period. Regional distribution of the causative agent was also observed in Cholera, Typhoid, and Amoebiasis cases. A08: viral and other specified intestinal infections and A09: other gastroenteritis and colitis of infectious and unspecified origin were the two most common causes of diarrheal diseases.

CONCLUSIONS: The incidence rate of acute diarrhea in Thai children under five years of age was higher while the mortality rate of acute diarrhea was lower than those in the past decade. A similar seasonal outbreak of acute diarrhea was seen during each examined year. The causative agent was not significant and was mainly unspecific.

TRIAL REGISTRATION: Number TCTR20220117002, date of registration: 17/01/2022, site: Thai Clinical Trials Registry, URL http://www.thaiclinicaltrials.org/show/TCTR20220117002.

PMID:35689279 | DOI:10.1186/s12889-022-13598-8

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Compliance with the World Health Organization’s surgical safety checklist and related postoperative outcomes: a nationwide survey among 172 health facilities in Ethiopia

Patient Saf Surg. 2022 Jun 10;16(1):20. doi: 10.1186/s13037-022-00329-6.

ABSTRACT

BACKGROUND: Ministry of Health (MOH) of Ethiopia adopted World Health Organization’s evidence-proven surgical safety checklist (SSC) to reduce the occurrence of surgical complications, i.e., death, disability and prolong hospitalization. MOH commissioned this evaluation to learn about SSC completeness and compliance, and its effect on magnitude of surgical complications.

METHODS: Health institution-based cross-sectional study with retrospective surgical chart audit was used to evaluate SSC utilization in 172 public and private health facilities in Ethiopia, December 2020-May 2021. A total of 1720 major emergency and elective surgeries in 172 (140 public and 32 private) facilities were recruited for chart review by an experienced team of surgical clinicians. A pre-tested tool was used to abstract data from patient charts and national database. Analyzed descriptive, univariable and bivariable data using Stata version-15 statistical software.

RESULTS: In 172 public and private health facilities across Ethiopia, 1603 of 1720 (93.2%) patient charts were audited; representations of public and private facilities were 81.4% (n = 140) and 18.6% (n = 32), respectively. Of surgeries that utilized SSC (67.6%, 1083 of 1603), the proportion of SSC that were filled completely and correctly were 60.8% (659 of 1083). Surgeries compliant to SSC guide achieved a statistically significant reduction in perioperative mortality (P = 0.002) and anesthesia adverse events (P = 0.005), but not in Surgical Site Infection (P = 0.086). Non-compliant surgeries neither utilized SSC nor completed the SSC correctly, 58.9% (944 of 1603).

CONCLUSIONS: Surgeries that adhered to the SSC achieved a statistically significant reduction in perioperative complications, including mortality. Disappointingly, a significant number of surgeries (58.9%) failed to adhere to SSC, a missed opportunity for reducing complications.

PMID:35689263 | DOI:10.1186/s13037-022-00329-6

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Parental care and depressive symptoms among Chinese medical students: roles of empathy and gender

BMC Med Educ. 2022 Jun 11;22(1):451. doi: 10.1186/s12909-022-03524-2.

ABSTRACT

BACKGROUND: Medical students in China who face the dual pressure of study and employment tend to experience subclinical depressive symptoms. Parental care plays an important direct and indirect role in the psychological development of medical students, and the extent and mechanism of this role urgently need to be studied and discussed.

METHODS: After simple random sampling and screening of valid questionnaires, data from a total of 924 people were used. The participants completed the parental bonding instrument, self-rating depression scale, Chinese version of the Jefferson empathy scale-medical student edition and self-rating anxiety scale to evaluate parental care, empathy, depressive symptoms and anxiety. The data were statistically processed using a descriptive analysis, correlation analysis and test of moderated mediation.

RESULTS: Maternal care had a significant negative predictive effect on depressive symptoms among medical students. Strong maternal care can reduce the occurrence of depressive symptoms in medical students. Empathy played a positive mediating role such that both types of empathy could alleviate the effect of weak maternal care on the depressive symptoms of medical students. However, neither cognitive empathy nor affective empathy played a mediating role in the relationship between paternal care and depressive symptoms. Nevertheless, the relationship between maternal care and empathy was moderated by the medical students’ gender.

CONCLUSIONS: The effect of this relationship on female medical students deserves special attention. The results of this study provide a reference and basis for the adjustment of medical education. This study could also help in the design of effective psychological intervention measures to reduce the degree of depressive symptoms and enhance personal empathy.

PMID:35689260 | DOI:10.1186/s12909-022-03524-2

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Organizing the health interview survey at the local level: design of a pilot study

Arch Public Health. 2022 Jun 10;80(1):155. doi: 10.1186/s13690-022-00909-z.

ABSTRACT

BACKGROUND: The local Health Interview Study (LHIS) was developed to gain health information at the level of the municipality in Flanders, the northern part of Belgium. It enables municipalities to make evidence-based decisions in their public health policy. To test the feasibility of implementing the LHIS, a pilot study was conducted in Melle, a small Flemish municipality with 11.736 inhabitants.

METHODS: The target sample size was 1000 (≥ 15 years). A systematic sampling technique was applied with substitutes for non-respondents who were matched in terms of statistical sector, age and sex. Selected persons were contacted by post to complete the questionnaire and in case of non-response, a reminder was sent. Questionnaires were collected using a concurrent mixed-mode design: a paper and pencil, and web option. All questions were selected from the Belgian Health Interview Survey relating to health status and determinants of health.

RESULTS: One thousand twenty-two questionnaires were obtained after inviting 3137 individuals (response rate = 32.6%). Older adults were more likely to participate than younger adults, and women more than men. The final sample resembled the initial sample in terms of sex and statistical sector, but not in terms of age. Younger adults were underrepresented whereas older adults were overrepresented. Lastly, older adults were more likely to fill in the questionnaire on paper than younger adults, and women more than men.

CONCLUSION: The LHIS can be successfully implemented in Flemish municipalities. The method, however, does not guarantee that the composition of the final sample reflects the initial sample. Therefore, weights should be added in the analyses to correct for potential deviations in sample composition. Furthermore, implementing a sequential mixed-mode design with a web option preceding a paper and pencil option in future studies could reduce costs and improve data quality.

PMID:35689255 | DOI:10.1186/s13690-022-00909-z

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Effects of COVID-19 lockdown on weight in a cohort of allergic children and adolescents

Ital J Pediatr. 2022 Jun 10;48(1):88. doi: 10.1186/s13052-022-01273-y.

ABSTRACT

BACKGROUND: COVID-19 lockdown caused sudden changes in people’s lifestyle, as a consequence of the forced lockdown imposed by governments all over the world. We aimed to evaluate the impact of lockdown on body mass index (BMI) in a cohort of allergic children and adolescents.

METHODS: From the first of June until the end of October 2020, we submitted a written questionnaire to all the patients who, after lockdown, carried out a visit at the Pediatric Allergy Unit of the Department of Mother-Child, Urological Science, Sapienza University of Rome. The questionnaire was composed by 10 questions, referring to the changes in their daily activities. Data were extrapolated from the questionnaire and then analyzed considering six variables: BMI before and BMI after lockdown, sugar intake, sport, screens, sleep, and anxiety.

RESULTS: One hundred fifty-three patients agreed to answer our questionnaire. Results showed a statistically significant increase in the BMI after lockdown (20.97 kg/m2 ± 2.63) with respect to the BMI before lockdown (19.18 kg/m2 ± 2.70). A multivariate regression analysis showed that the two variables that mostly influenced the increase in BMI were sleep and anxiety.

CONCLUSIONS: For the analyzed cohort of allergic children and adolescents we obtained significant gain in BMI as consequences of lockdown, which can be explained by many factors: high consumption of consolatory food, less sport activities, more time spent in front of screens, sleep alteration associated with increased anxiety. All these factors acted together, although sleep alteration and increased anxiety were the most influential factors that led to the worsening or the onset of weight gain, creating the basis for future health problems.

PMID:35689248 | DOI:10.1186/s13052-022-01273-y

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Neutralising reactivity against SARS-CoV-2 Delta and Omicron variants by vaccination and infection history

Genome Med. 2022 Jun 10;14(1):61. doi: 10.1186/s13073-022-01066-2.

ABSTRACT

BACKGROUND: The continuous emergence of SARS-CoV-2 variants of concern (VOC) with immune escape properties, such as Delta (B.1.617.2) and Omicron (B.1.1.529), questions the extent of the antibody-mediated protection against the virus. Here we investigated the long-term antibody persistence in previously infected subjects and the extent of the antibody-mediated protection against B.1, B.1.617.2 and BA.1 variants in unvaccinated subjects previously infected, vaccinated naïve and vaccinated previously infected subjects.

METHODS: Blood samples collected 15 months post-infection from unvaccinated (n=35) and vaccinated (n=41) previously infected subjects (Vo’ cohort) were tested for the presence of antibodies against the SARS-CoV-2 spike (S) and nucleocapsid (N) antigens using the Abbott, DiaSorin, and Roche immunoassays. The serum neutralising reactivity was assessed against B.1, B.1.617.2 (Delta), and BA.1 (Omicron) SARS-CoV-2 strains through micro-neutralisation. The antibody titres were compared to those from previous timepoints, performed at 2- and 9-months post-infection on the same individuals. Two groups of naïve subjects were used as controls, one from the same cohort (unvaccinated n=29 and vaccinated n=20) and a group of vaccinated naïve healthcare workers (n=61).

RESULTS: We report on the results of the third serosurvey run in the Vo’ cohort. With respect to the 9-month time point, antibodies against the S antigen significantly decreased (P=0.0063) among unvaccinated subjects and increased (P<0.0001) in vaccinated individuals, whereas those against the N antigen decreased in the whole cohort. When compared with control groups (naïve Vo’ inhabitants and naïve healthcare workers), vaccinated subjects that were previously infected had higher antibody levels (P<0.0001) than vaccinated naïve subjects. Two doses of vaccine elicited stronger anti-S antibody response than natural infection (P<0.0001). Finally, the neutralising reactivity of sera against B.1.617.2 and BA.1 was 4-fold and 16-fold lower than the reactivity observed against the original B.1 strain.

CONCLUSIONS: These results confirm that vaccination induces strong antibody response in most individuals, and even stronger in previously infected subjects. Neutralising reactivity elicited by natural infection followed by vaccination is increasingly weakened by the recent emergence of VOCs. While immunity is not completely compromised, a change in vaccine development may be required going forward, to generate cross-protective pan-coronavirus immunity in the global population.

PMID:35689243 | DOI:10.1186/s13073-022-01066-2

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Are prevention of mother-to-child HIV transmission service providers acquainted with national guideline recommendations? A cross-sectional study of primary health care centers in Lagos, Nigeria

BMC Health Serv Res. 2022 Jun 11;22(1):769. doi: 10.1186/s12913-022-08152-6.

ABSTRACT

BACKGROUND: Implementation of interventions for the prevention of mother-to-child transmission (PMTCT) of HIV in low- and middle-income countries, faces several barriers including health systems challenges such as health providers’ knowledge and use of recommended guidelines. This study assessed PMTCT providers’ knowledge of national PMTCT guideline recommendations in Lagos, Nigeria.

METHODS: This was a cross-sectional survey of a purposive sample of twenty-three primary health care (PHC) centers in the five districts of Lagos, Nigeria. Participants completed a self-administered 16-item knowledge assessment tool created from the 2016 Nigeria PMTCT guidelines. Research Electronic Data Capture (REDCap) was used for data entry and R statistical software used for data analysis. The Chi square test with a threshold of P < 0.05 considered as significant was used to test the hypothesis that at least 20% of service providers will have good knowledge of the PMTCT guidelines.

RESULTS: One hundred and thirteen (113) respondents participated in the survey. Most respondents knew that HIV screening at the first prenatal clinic was an entry point to PMTCT services (97%) and that posttest counselling of HIV-negative women was necessary (82%). Similarly, most respondents (89%) knew that early infant diagnosis (EID) of HIV should occur at 6-8 weeks of life (89%). However, only four (3.5%) respondents knew the group counselling and opt-out screening recommendation of the guidelines; 63% did not know that haematocrit check should be at every antenatal clinic visit. Forty-eight (42.5%) service providers had good knowledge scores, making the hypothesis accepted. Knowledge score was not influenced by health worker cadre (p = 0.436), training(P = 0.537) and professional qualification of ≤5 years (P = 0.43).

CONCLUSION: Service providers’ knowledge of the PMTCT guidelines recommendations varied. The knowledge of group counselling and opt-out screening recommendations was poor despite the good knowledge of infant nevirapine prophylaxis. The findings highlight the need for training of service providers.

PMID:35689236 | DOI:10.1186/s12913-022-08152-6