Objectives: To determine the influence of induced fatigue on dynamic balance in healthy athletes.

Design: Systematic review.

Data sources: PUBMED, MEDLINE, CINAHL, Sports Discus, and the Cochrane library from onset to May 28, 2019.

Eligibility criteria: Eligible studies included any study examining the effects of induced-fatigue on dynamic balance, as measured by the SEBT/YBT, in healthy athletic populations. Studies with a low risk of bias were considered scientifically admissible for a best evidence synthesis.

Results: Fifteen studies with low risk of bias were included - seven investigated recreational athletes while eight focused on competitive athletes. In the recreational population, five of the studies found significant decrease in dynamic balance following the fatiguing intervention. However, the remaining two concluded with insignificant changes. As for the competitive population, three studies showed significant effects of induced fatigue on dynamic balance, while five showed no effects.

Conclusion: There are conflicting results regarding the effects of induced fatigue on dynamic balance. The majority of studies focused on competitive athletes found that fatigue did not alter their dynamic balance. Per contra, the majority of studies focused on recreational athletes concluded the opposite - fatigue did indeed affect dynamic balance.

Objectifs: Déterminer si la fatigue musculaire a des effets sur l’équilibre dynamique chez les athlètes en bon état de santé.

Méthodologie: Revue systématique.

Sources des données: PUBMED, MEDLINE, CINAHL, Sports Discus et la bibliothèque Cochrane du début des publications jusqu’au 28 mai 2019.

Critères d’admission: Les études admissibles comprenaient toutes celles qui avaient porté sur les effets de la fatigue musculaire sur l’équilibre dynamique, telle qu’elle mesurée par le SEBT/YBT dans des populations de sportifs sains. Les études comportant un faible risque de biais ont été considérées comme scientifiquement admissibles pour faire une synthèse des meilleures données probantes.

Résultats: Quinze études présentant un faible risque de biais ont été retenues; sept portaient sur des athlètes amateurs et les huit autres, sur des athlètes de compétition. En ce qui concerne les athlètes amateurs, cinq études ont montré une diminution importante de l’équilibre dynamique après une activité causant de la fatigue. Cependant, dans les deux autres études, les changements n’étaient pas importants. En ce qui concerne les athlètes de compétition, trois études ont montré que la fatigue musculaire avait d’importants effets sur l’équilibre dynamique, tandis que cinq n’en ont montré aucun.

Conclusion: Les résultats des études sur les effets de la fatigue musculaire sur l’équilibre dynamique sont contradictoires. La majorité des études portant sur des athlètes de compétition ont montré que la fatigue n’avait aucun effet sur l’équilibre dynamique. Par contre, la majorité portant sur les athlètes récréatifs ont conclu le contraire, c’est-à-dire que la fatigue avait un effet sur l’équilibre dynamique.

Keywords: athlete; athlète; blessures aux jambes; dynamic balance; fatigue musculaire; leg injuries; muscle fatigue; postural balance; équilibre dynamique; équilibre postural.

Objectives: This study aims to determine whether manipulative therapy of the hip joint can increase range of motion (ROM) and/or decrease pain in individuals experiencing symptomatic hip pain.

Methods: Non-disabled young adults were recruited on campus of a chiropractic college for this randomized crossover study. Subjects' hip active and passive ROM and pain perception were measured. Subjects then received a drop-piece hip manipulation (DPHM) or an alternative treatment, followed by measurement of active and passive ROM and pain.

Results: Eight males and 12 females (n=20) between the ages of 21-32 years completed the study. Statistically significant improvements in numeric pain scale (NRS) and passive abduction were observed for the manipulation group when compared to the alternative treatment. No significant change was observed for all other hip ranges.

Conclusions: DPHM of the symptomatic hip joint in a small sample of young adults resulted in statistically significant improvements in pain and passive abduction when compared to sham manipulation. Due to low sample size, further research is recommended.

Objectifs: Cette étude vise à déterminer si les manipulations de la hanche peuvent augmenter l’amplitude du mouvement et/ou diminuer la douleur chez les personnes ayant des douleurs à la hanche.

Méthodologie: On a recruté de jeunes adultes non handicapés sur le campus d’un collège chiropratique pour participer cette étude croisée à répartition aléatoire. L’amplitude des mouvements actifs et passifs de la hanche et la perception de la douleur ont été mesurées. Les sujets ont ensuite subi des manipulations de la hanche sur une table à sections mobiles qui chutent ou un autre traitement, puis on a mesuré l’amplitude des mouvements actifs et passifs et l’intensité de la douleur.

Résultats: Huit hommes et 12 femmes (n=20) âgés de 21 à 32 ans ont participé à l’étude. Des améliorations statistiquement significatives sur l’échelle numérique de la douleur et de l’abduction passive ont été observées dans le groupe ayant eu des manipulations par rapport à l’autre traitement. Aucun changement significatif d’amplitude n’a été observé pour les autres mouvements de la hanche.

Conclusions: Les manipulations sur table à sections mobiles qui chutent pour traiter la hanche symptomatique sur un petit échantillon de jeunes adultes a permis d’obtenir des améliorations statistiquement significatives de la douleur et de l’abduction passive par rapport à la manipulation fictive. En raison de la faible taille de l’échantillon, des recherches supplémentaires sont recommandées.

Keywords: ROM; amplitude du mouvement; articulation de la hanche; chiropractic; chiropratique; douleur; drop piece; hip joint; manipulation; pain; symptomatic; symptomatique; table chiropratique à sections mobiles qui chutent.

Background: Non-alcoholic fatty liver disease (NAFLD) is an increasingly common cause of chronic liver disease and is becoming a major public health problem. NAFLD has been recognized as a hepatic manifestation of metabolic syndrome, associated with systemic diseases such as cardiovascular disease (CVD) and chronic kidney disease (CKD).

Objective: The aim of this study was to examine the role of serum LFT parameters and renal function parameters as predictors of unmanifested liver disease.

Methods: In this study, the presence of possible liver disease detected by biochemical parameters and confirmed by Transient Liver Elastography (TE) in a group of patients with different stages of chronic kidney disease (CKD) was investigated. Patients with various stages of CKD were divided into five subgroups regarding aetiology: nephroangiosclerosis, diabetic nephropathy, glomerulonephritis and pyelonephritis, autoimmune kidney disease, and polycystic and another morphological kidney disease. Liver stiffness was used to quantify liver fibrosis while Controlled attenuation parameter (CAP) was used to quantify liver steatosis. Functional liver tests and biochemical parameters of kidney function were measured in all patients.

Results: Statistical analysis used in this study was a decision tree as a predictive model to map observed variables resulting in the conclusion about outcomes. The application of existing laboratory parameters, in combination with other parameters in presence of the defined etiological factors of kidneys diseases, indicate development of hepatic diseases. Higher values of phosphorus and low values of ferritin in patients with autoimmune kidney disease, and polycystic and another morphological kidney disease, expresses steatosis of the hepatic parenchyma.

Conclusion: In contrary, low values of phosphorus and higher values of ferritin in patients with nephroangiosclerosis, diabetic nephropathy, glomerulonephritis and pyelonephritis, are in a favour steatosis of the hepatic parenchyma. Serum values of phosphorus and ferritin are valuable predictors of the liver disease in patients with end-stage kidney diseases of different aetiology.

Keywords: Biochemical parameters; Chronic Kidney Disorders; Liver disease.

Emotion-driven impulse control difficulties are associated with negative psychological outcomes. Extant research suggests that high frequency heart rate variability (HF-HRV) may be indicative of emotion-driven impulse control difficulties and potentially moderated by negative emotion. In the current study, 248 eleven- to 14-year-olds and their parent engaged in a negatively emotionally arousing conflict task at Time 1. Adolescents' HF-HRV and negative emotional expression and experience were assessed before, during, and/or after the task. Adolescents reported on their levels of emotion-driven impulse control difficulties at Time 1 and one year later. Results revealed that higher levels of HF-HRV reactivity (i.e., higher HF-HRV augmentation) predicted higher levels of emotion-driven impulse control difficulties one year later among adolescents who experienced higher negative emotion. These findings suggest that negative emotional context should be considered when examining HF-HRV reactivity as a risk factor for emotion-driven impulse control difficulties and associated outcomes.

Keywords: adolescent; emotion; heart rate variability; impulse control; respiratory sinus arrhythmia.

The COVID-19 pandemic initiated a deep global recession, and with interest rates at very low levels, warrants consideration of the efficacy of different forms of fiscal stimulus in response. History reveals that deep recessions may cause output and total factor productivity (TFP) hysteresis, a permanent or highly persistent fall in the levels of output and TFP relative to pre-recession trends. This article analyses the output and welfare multipliers of fiscal stimulus during a recession using a macro model with TFP and output hysteresis. We find that transfer payments, public consumption and investment all have high output and welfare multipliers due to their positive effects on TFP in a recessionary environment. However, public investment has the highest output and welfare multipliers, because it has a more positive impact on labour productivity due to the increase in the public capital stock.

Keywords: Covid-19; Fiscal policy; Hysteresis; Recession.

Background: Chemotherapy can induce premature ovarian insufficiency (POI). POI causes multiple sequelae and is currently incurable. As shown in our previous studies, systemically transplanted human amnion-derived mesenchymal stem cells (hAD-MSCs) home to ovaries with chemotherapy-induced POI and subsequently reduce ovarian injury and improve ovarian function in rats with POI. However, the cellular mechanisms that direct the migration and homing of hAD-MSCs to ovaries with chemotherapy-induced POI are incompletely understood. This study investigated the role of the SDF-1/CXCR4 axis in the migration and homing of systemically transplanted hAD-MSCs to ovaries with chemotherapy-induced POI and its relevant downstream signalling pathways.

Methods: CXCR4 expression in hAD-MSCs was assessed using Western blotting and immunofluorescence staining. hAD-MSC migration was tested using Transwell migration assays. SDF-1 levels were detected using ELISA. Seventy-two female SD rats were randomly divided into the control, POI, hAD-MSCs and hAD-MSCs + AMD3100 groups. Cyclophosphamide was used to establish rat POI models. For inhibitor treatment, hAD-MSCs were pretreated with AMD3100 before transplantation. PKH26-labeled hAD-MSCs were injected into the tail vein of POI rats 24 h after chemotherapy. After hAD-MSC transplantation, the homing of hAD-MSCs to ovaries and ovarian function and pathological changes were examined. We further investigated the molecular mechanisms by detecting the PI3K/Akt and ERK1/2 signalling pathways.

Results: hAD-MSCs expressed CXCR4. SDF-1 induced hAD-MSC migration in vitro. SDF-1 levels in ovaries and serum were significantly increased in rats with chemotherapy-induced POI, and ovaries with POI induced the homing of hAD-MSCs expressing CXCR4. Blocking the SDF-1/CXCR4 axis with AMD3100 significantly reduced the number of hAD-MSCs homing to ovaries with POI and further reduced their efficacy in POI treatment. The binding of SDF-1 to CXCR4 activated the PI3K/Akt signalling pathway, and LY294002 significantly inhibited hAD-MSC migration induced by SDF-1 in vitro. Moreover, inhibition of the PI3K/Akt signalling pathway significantly reduced the number of systemically transplanted hAD-MSCs homing to chemotherapy-induced ovaries in rats with POI.

Conclusions: SDF-1/CXCR4 axis partially mediates the migration and homing of systemically transplanted hAD-MSCs to the ovaries of rats with chemotherapy-induced POI, and the PI3K/Akt signalling pathway might be involved in the migration and homing of hAD-MSCs mediated by the SDF-1/CXCR4 axis.

Keywords: CXC chemokine receptor 4 (CXCR4); Human amnion-derived mesenchymal stem cells (hAD-MSCs); Premature ovarian insufficiency (POI); Stem cell homing; Stromal cell-derived factor-1 (SDF-1); Transplantation.

Background: Continual expression of PD-L1 in tumor cells is critical for tumor immune escape and host T cell exhaustion, however, knowledge on its clinical benefits through inhibition is limited in breast cancer. N⁶-methyladenosine (m⁶A) plays a crucial role in multiple biological activities. Our study aimed to investigate the regulatory role of the m⁶A modification in PD-L1 expression and immune surveillance in breast cancer.

Methods: MeRIP-seq and epitranscriptomic microarray identified that PD-L1 is the downstream target of METTL3. MeRIP-qPCR, absolute quantification of m⁶A modification assay, and RIP-qPCR were used to examine the molecular mechanism underlying METTL3/m⁶A/IGF2BP3 signaling axis in PD-L1 expression. B-NDG and BALB/c mice were used to construct xenograft tumor models to verify the phenotypes upon METTL3 and IGF2BP3 silencing. In addition, breast cancer tissue microarray was used to analyze the correlation between PD-L1 and METTL3 or IGF2BP3 expression.

Results: We identified that PD-L1 was a downstream target of METTL3-mediated m⁶A modification in breast cancer cells. METTL3 knockdown significantly abolished m⁶A modification and reduced stabilization of PD-L1 mRNA. Additionally, METTL3-mediated PD-L1 mRNA activation was m⁶A-IGF2BP3-dependent. Moreover, inhibition of METTL3 or IGF2BP3 enhanced anti-tumor immunity through PD-L1-mediated T cell activation, exhaustion, and infiltration both in vitro and in vivo. PD-L1 expression was also positively correlated with METTL3 and IGF2BP3 expression in breast cancer tissues.

Conclusion: Our study suggested that METTL3 could post-transcriptionally upregulate PD-L1 expression in an m⁶A-IGF2BP3-dependent manner to further promote stabilization of PD-L1 mRNA, which may have important implications for new and efficient therapeutic strategies in the tumor immunotherapy.

Keywords: Breast cancer; Immune surveillance; METTL3; PD-L1; m6A.

Background: Dementia education is required to address gaps in dementia-specific knowledge among health and social care practitioners amidst increasing dementia prevalence. Harnessing technology for dementia education may remove obstacles to traditional education and empower large communities of learners. This systematic review aimed to establish the technological and pedagogical characteristics associated with effective technology-enabled dementia education for health and social care practitioners.

Methods: MEDLINE, PubMed, Web of Science, CINAHL, Scopus, PsycINFO, ERIC and OVID Nursing Database were searched from January 2005 until February 2020. Quantitative, qualitative and mixed methods studies were eligible for inclusion. Study quality was assessed with the Mixed Methods Appraisal Tool. Quantitative evidence was categorised based on Kirkpatrick's Model. Qualitative data was synthesised thematically and integrated with quantitative findings before conclusions were drawn.

Results: Twenty-one published papers were identified. Participants were acute, primary and long-term care practitioners, or were students in higher education. Most training was internet-based; CD-ROMs, simulations and tele-mentoring were also described. Technology-enabled dementia education was predominantly associated with positive effects on learning outcomes. Case-based instruction was the most frequently described instructional strategy and videos were common modes of information delivery. Qualitative themes emerged as existing strengths and experience; knowledge gaps and uncertainty; developing core competence and expertise; involving relevant others; and optimising feasibility.

Discussion: Technology-enabled dementia education is likely to improve dementia knowledge, skills and attitudes among health and social care practitioners from multiple practice contexts. Confidence in the results from quantitative studies was undermined by multiple confounding factors that may be difficult to control in the educational research context. Convenience and flexibility are key benefits of technology-enabled instructive and simulated pedagogy that can support the application of theory into practice. More research is required to understand the role of online learning networks and provisions for equitable engagement. A future emphasis on organisational and environmental factors may elucidate the role of technology in ameliorating obstacles to traditional dementia education.

Systematic review registration: PROSPERO ( CRD42018115378 ).

Keywords: Dementia; Dementia education; Dementia training; Mixed research; Systematic review; Technology-enabled learning.

Background: The combination of pemetrexed and cisplatin remains the reference first-line systemic therapy for malignant pleural mesothelioma (MPM). Its activity is moderate because of tumor aggressiveness, immune-suppressive environment and resistance to chemotherapy-induced immunogenic cell death (ICD). Preliminary and limited findings suggest that MPM cells have deregulated ubiquitination and proteasome activities, although proteasome inhibitors achieved disappointing clinical results.

Methods: Here, we investigated the role of the E3-ubiquitin ligase SKP/Cullin/F-box (SCF) complex in cell cycle progression, endoplasmic reticulum (ER)/proteostatic stress and ICD in MPM, and the therapeutic potential of the neddylation/SCF complex inhibitor MLN4924/Pevonedistat.

Results: In patient-derived MPM cultures and syngenic murine models, MLN4924 and cisplatin showed anti-tumor effects, regardless of MPM histotype and BAP1 mutational status, increasing DNA damage, inducing S- and G2/M-cell cycle arrest, and apoptosis. Mechanistically, by interfering with the neddylation of cullin-1 and ubiquitin-conjugating enzyme UBE2M, MLN4924 blocks the SCF complex activity and triggers an ER stress-dependent ICD, which activated anti-MPM CD8⁺T-lymphocytes. The SKP2 component of SCF complex was identified as the main driver of sensitivity to MLN4924 and resistance to cisplatin. These findings were confirmed in a retrospective MPM patient series, where SKP2 high levels were associated with a worse response to platinum-based therapy and inferior survival.

Conclusions: We suggest that the combination of neddylation inhibitors and cisplatin could be worth of further investigation in the clinical setting for MPM unresponsive to cisplatin. We also propose SKP2 as a new stratification marker to determine the sensitivity to cisplatin and drugs interfering with ubiquitination/proteasome systems in MPM.

Keywords: Malignant pleural mesothelioma; Pevonedistat; SKP/Cullin/F-box complex; endoplasmic reticulum stress; immunogenic cell death.

Background: Total hip replacement (THR) in the gold standard surgical treatment for the canine hip. While it has been shown that greater trochanter morphology affects post-operative cementless stem position in humans, trochanter morphology and the effect on cementless stem position has not been extensively evaluated in dogs. The objective of this study was to classify greater trochanter morphology and identify potential associations between trochanter morphology and patient demographics, femoral canal geometry, surgical time, technique modifications, and post-operative stem position in client-owned dogs undergoing cementless THR.

Results: In this retrospective study, medical records and radiographs of 135 dogs undergoing 150 cementless total hip replacements from 2013 to 2020 were included. Trochanters were classified in the frontal plane using an ordinal grading system adapted from human THR. A Grade I trochanter denoted a trochanter positioned lateral to the periosteal surface of the lateral femoral cortex, whereas a Grade IV trochanter denoted a trochanter positioned medial to the anatomic axis of the femur. Associations between trochanter grade and other variables were examined using ANOVA, Kruskall-Wallis, or chi-squared tests. Significance was assumed at P ≤ .05. Trochanters were classified as follows: Grade I (44/150, 29.3%), Grade II (56/150, 37.4%), Grade III (44/150, 29.3%), Grade IV (6/150, 4.0%). Grade IV trochanters had lower anatomic lateral distal femoral angle (aLDFA; 91.0 ± 6.2°), angle of inclination (117.7 ± 10.5°), and canal flare index (1.53 ± 0.27). When compared to all groups, Grade IV trochanters were associated with longer surgical times (Grade IV: 227.0 ± 34.2 min; all grades: 183.2 ± 32.9 min) and technique modifications (Grade IV: 83.3%; all grades: 18%). Grade I trochanters had stems placed in valgus (- 1.8 ± 2.33°), whereas Grade II (0.52 ± 2.36°), III (0.77 ± 2.58°), and IV (0.67 ± 2.73°) trochanters exhibited varus stems. Depth of stem insertion was greater (11.2 ± 4.2 mm) for Grade IV trochanters.

Conclusions: Trochanter grade was associated with post-operative stem alignment and translation in the frontal plane. Grade IV trochanters were associated with altered femoral geometry, increased surgical time, technique modifications, and stem insertion depth. Pre-operative greater trochanter classification may prove useful in identifying cases requiring prolonged surgical times or technique modifications.

Keywords: Cementless THR; Classification; Greater trochanter; THR; Total hip replacement.

Background: Most sub-Saharan Africa countries adopt global health policies. However, mechanisms with which policy transfers occur have largely been studied amongst developed countries and much less in low- and middle- income countries. The current review sought to contribute to literature in this area by exploring how health policy agendas have been transferred from global to national level in sub-Saharan Africa. This is particularly important in the Sustainable Development Goals (SDGs) era as there are many policy prepositions by global actors to be transferred to national level for example the World Health Organization (WHO) policy principles of health financing reforms that advance Universal Health Coverage (UHC).

Methods: We conducted a critical review of literature following Arksey and O'Malley framework for conducting reviews. We searched EBSCOhost, ProQuest, PubMed, Scopus, Web of Science and Google scholar for articles. We combined the concepts and synonyms of "policy transfer" with those of "sub-Saharan Africa" using Boolean operators in searching databases. Data were analyzed thematically, and results presented narratively.

Results: Nine articles satisfied our eligibility criteria. The predominant policy transfer mechanism in the health sector in sub-Saharan Africa is voluntarism. There are cases of coercion, however, even in the face of coercion, there is usually some level of negotiation. Agency, context and nature of the issue are key influencers in policy transfers. The transfer is likely to be smooth if it is mainly technical and changes are within the confines of a given disease programmatic area. Policies with potential implications on bureaucratic and political status quo are more challenging to transfer.

Conclusion: Policy transfer, irrespective of the mechanism, requires local alignment and appreciation of context by the principal agents, availability of financial resources, a coordination platform and good working relations amongst stakeholders. Potential effects of the policy on the bureaucratic structure and political status are also important during the policy transfer process.

Keywords: Health; Policy transfer; Review of literature; Sub-Saharan Africa.

Background: Naloxone-based interventions as part of health systems can reverse an opioid overdose. Previous systematic reviews have identified the effectiveness of naloxone; however, the role of context and mechanisms for its use has not been explored. This realist systematic review aims to identify a theory of how naloxone works based on the contexts and mechanisms that contribute to the success of the intervention for improved outcomes.

Methods: Pre-registered at PROSPERO, this realist review followed RAMESES standards of reporting. Keywords included 'naloxone' and ' opioid overdose'. All study designs were included. Data extraction using 55 relevant outputs based on realist logic produced evidence of two middle-range theories: Naloxone Bystander Intervention Theory and Skills Transfer Theory.

Results: Harm reduction and/or low threshold contexts provide a non-judgemental approach which support in-group norms of helping and empower the social identity of the trained and untrained bystander. This context also creates the conditions necessary for skills transfer and diffusion of the intervention into social networks. Stigma and negative attitudes held by first responders and stakeholders involved in the implementation process, such as police or GPs, can prohibit the bystander response by inducing fear in responding. This interferes with skills transfer, naloxone use and carriage of naloxone kits.

Conclusions: The findings provide theoretically informed guidance regarding the harm reduction contexts that are essential for the successful implementation of naloxone-based interventions. Peer-to-peer models of training are helpful as it reinforces social identity and successful skills transfer between bystanders. Health systems may want to assess the prevalence of, and take steps to reduce opioid-related stigma with key stakeholders in contexts using a low threshold training approach to build an environment to support positive naloxone outcomes.

Trial registration: PROSPERO 2019 CRD42019141003.

Keywords: Bystander response; Drug-related deaths; Naloxone; Opioid overdose; Realist review.

Background: Shone's complex is a rare congenital heart disease consisting of a variety of left ventricular inflow and outflow tract lesions. Patients typically present in childhood requiring early surgical intervention; however, with improved surgical techniques, these patients are surviving later into adulthood. This increased survival comes with a new set of medical complications that providers need to be aware of.

Case presentation: A 27 year old man with a complex cardiac history including an incomplete Shone's complex and persistent symptomatic atrial flutter presented with sharp chest pain radiating to his back. He was found to have type A aortic dissection on imaging in the setting of severe patient-prosthesis mismatch. He had multiple valvular surgeries in childhood. The patient was being followed-up as an outpatient for an enlarging chronic aortic aneurysm and was non-compliant with his medications. He was taken emergently to the operating room for a skirted Bentall procedure, aortic valve replacement, and right sided MAZE.

Conclusions: Shone's complex is a rare congenital heart disease associated with significant morbidities including atrial flutter, patient-prosthesis mismatch, and aortic dissection. As patients continue to live longer into adulthood with this disease, it is important to raise awareness of this rare syndrome for providers and highlight its potential complications. Further research is needed to determine appropriate guidelines for when to intervene on aortopathy-associated CHD.

Keywords: Aortic aneurysm; Aortic dissection; Bentall procedure; Congenital heart disease; LVOT obstruction; MAZE procedure; Patient prosthesis mismatch; Shone’s complex; Shone’s syndrome.

Background: Pharmaceutical compounding ensures access of individuals with specific requirements to individualized therapy. However, there is an inconsistency of compounded medication quality. Therefore, advancing the rational use of compounded medication is essential for patient safety and medication effectiveness.

Objective: The presented study was aimed to investigate the healthcare practitioners' knowledge, perception, and practice of extemporaneous compounding and its contribution to the prevalence of antimicrobial resistance.

Method: A descriptive cross-sectional survey using a structured questionnaire was conducted. The study participants were 300 healthcare practitioners working in Jimma University Medical Center, hospital pharmacies, and community pharmacies in Jimma and Mettu Town, Southwest Ethiopia.

Results: Most respondents were pharmacists (62.7%) and first-degree holders (48.3%). The majority of them had experience in administering (57.7%), preparing (38%), prescribing (21%), and repackaging and labeling (14%) compounded medications. Commonly they request compounded medications when prepackaged products (77.7%) and needed dosage regimens (72.3%) were not available in the market. However, most of them believed that compounded medications might lack quality (49%) and had poor patient compliance (40.7%). Moreover, they fear that inappropriate preparation processes (75%) and under-dose administration (59%) of compounded medication might contribute to the development and prevalence of antimicrobial resistance.

Conclusion: Most healthcare practitioners practice rational use of compounded medications and strongly agree that inappropriate compounding of antimicrobials contributes to antimicrobial resistance development.

Keywords: Antimicrobial resistance; Compounding; Healthcare practitioners; Rational use.

The antiviral immune response to SARS-CoV-2 infection can limit viral spread and prevent development of pneumonic COVID-19. However, the protective immunological response associated with successful viral containment in the upper airways remains unclear. Here, we combine a multi-omics approach with longitudinal sampling to reveal temporally resolved protective immune signatures in non-pneumonic and ambulatory SARS-CoV-2 infected patients and associate specific immune trajectories with upper airway viral containment. We see a distinct systemic rather than local immune state associated with viral containment, characterized by interferon stimulated gene (ISG) upregulation across circulating immune cell subsets in non-pneumonic SARS-CoV2 infection. We report reduced cytotoxic potential of Natural Killer (NK) and T cells, and an immune-modulatory monocyte phenotype associated with protective immunity in COVID-19. Together, we show protective immune trajectories in SARS-CoV2 infection, which have important implications for patient prognosis and the development of immunomodulatory therapies.

Dysregulation of circadian rhythm can cause nocturia. Levels of fatty acid metabolites, such as palmitoylethanolamide (PEA), 9-hydroxy-10E,12Z-octadecadienoic acid (9-HODE), and 4-hydroxy-5E,7Z,10Z,13Z,16Z,19Z-docosahexaenoic acid (4-HDoHE), are higher in the serum of patients with nocturia; however, the reason remains unknown. Here, we investigated the circadian rhythm of fatty acid metabolites and their effect on voiding in mice. WT and Clock mutant (Clock^Δ19/Δ19) mice, a model for nocturia with circadian rhythm disorder, were used. Levels of serum PEA, 9-HODE, and 4-HDoHEl were measured every 8 h using LC/MS. Voiding pattern was recorded using metabolic cages after administration of PEA, 9-HODE, and 4-HDoHE to WT mice. Levels of serum PEA and 9-HODE fluctuated with circadian rhythm in WT mice, which were lower during the light phase. In contrast, circadian PEA and 9-HODE level deteriorated or retreated in Clock^Δ19/Δ19 mice. Levels of serum PEA, 9-HODE, and 4-HDoHE were higher in Clock^Δ19/Δ19 than in WT mice. Voiding frequency increased in PEA- and 4-HDoHE-administered mice. Bladder capacity decreased in PEA-administered mice. The changes of these bladder functions in mice were similar to those in elderly humans with nocturia. These findings highlighted the novel effect of lipids on the pathology of nocturia. These may be used for development of biomarkers and better therapies for nocturia.

Infectious diseases, chronic diseases, and mental disorders in both adults and children are reported after disasters occur. The correlation between chronic diseases and mental disorders has also been reported. Moreover, disasters may affect perinatal outcomes. Thus, both adult and child health should be carefully monitored in disaster aftermath. A prospective cohort study of pregnant women and their families, the Tohoku Medical Megabank Project (TMM) Birth and Three-Generation Cohort Study (TMM BirThree Cohort Study), has been conducted since 2013. A total of 73,529 family members participated in the TMM BirThree Cohort Study. Among siblings, the proportion of "small for gestational age" was the same in the pre- and post-disaster periods. Among parents and grandparents who answered the baseline questionnaire, 5.6% in the inland area and 19.8% in the coastal area had their houses totally/mostly destroyed by the Great East Japan Earthquake. Although a depression trend due to house damage was not observed in mothers, the proportion of psychological distress was high according to house damage (P for trend = 0.04). Among parents, there was an increase in overweight persons (P for trend = 0.004 in mothers and < 0.0001 in fathers) and in the number of smokers based on the severity of house damage (P for trend = 0.002 in mothers and < 0.0001 in fathers), whereas no such trend was observed in grandparents. Continuous monitoring and support for those who need are essential. Moreover, utilizing existing cohort studies to investigate health status when we face a new disaster is desirable.

Keywords: Great East Japan Earthquake; adults; children; health status after the disaster; prospective cohort study.

Aim and objective: The aim of the study was to evaluate the changes in free available chlorine (FAC) when 6% sodium hypochlorite (NaOCl) is admixed with irrigants 17% ethylenediaminetetraacetic acid (EDTA), 2% chlorhexidine (CHX), and 0.2% chitosan in varying proportions of 90:10, 80:20, and 50:50.

Materials and methods: The 25 mL aliquots of 6% NaOCl were admixed in varying proportions of 90:10, 80:20, and 50:50 with secondary irrigation solutions: (a) 17% EDTA, (b) 2% CHX, (c) 0.2% chitosan. Iodometric titration was done to evaluate the change in FAC.

Statistical analysis used: Kruskal-Wallis and Mann-Whitney tests.

Results: On titration, the mean FAC value of NaOCl at baseline was 1.99 g%. On mixing NaOCl with EDTA, the FAC decreased in all the three proportions and the values were 0.17 g%, 0.17 g%, and 0.06 g% at 90:10, 80:20, and 50:50 ratios, respectively. pH obtained was 9.55 at 50:50 ratio. On mixing NaOCl with CHX, FAC reduced and the values were 1.84 g%, 1.72 g%, and 0.27 g% at 90:10, 80:20, and 50:50 ratios, respectively. pH obtained was 10.87 at 50:50 ratio. On mixing NaOCl and chitosan, the FAC remained unaltered in all the three proportions and the values were 1.64 g%, 1.51 g%, and 1.63 g% at 90:10, 80:20, and 50:50 ratios, respectively. pH obtained was 11 at 50:50 ratio.

Conclusion: Combination of NaOCl and chitosan did not lead to a reduction in FAC and the pH of the solution remained unaltered, suggesting that tissue-dissolving property of NaOCl might be preserved.

Clinical significance: The combination of chitosan with NaOCl is advantageous in two ways. Firstly, FAC remained unaltered and the pH of the solution was also maintained at 11.05 indicating that the tissue-dissolving property of NaOCl prevailed. Secondly, chitosan is known for its chelating property and is effective in smear layer removal. With further in vivo and in vitro studies, a combination of chitosan and NaOCl can be proposed as a novel irrigant.

Keywords: Chitosan; Chlorhexidine; Ethylenediaminetetraacetic acid; Free available chlorine; Iodometric titration Sodium hypochlorite..

Aim and objective: In this study, we quantified the color of brackets and archwire appliances for an objective evaluation and investigated its relationship with subjective esthetic evaluation.

Materials and methods: Five types of commercially available brackets (ceramic brackets C1, C2, and C3; plastic brackets P1 and P2) and three types of archwires (coated nickel-titanium archwires W1, W2, and W3) were used. The reflectance (%) and color (lightness: L^*, hue: a^*, b^*) of each sample were quantified using a spectrophotometer (n = 5). Fifteen combinations of brackets and archwires were used. The esthetic evaluation was performed using the visual analog scale (VAS) method, and responses were obtained from 30 laypersons and 15 orthodontists. The mean VAS score was calculated, and the relationship between the reflectance and color of the bracket and archwire was discussed.

Results: The reflectance and L^* of the brackets showed significantly higher values for C3 and C1 than for the others and lower values for P1 and P2. The reflectance and L^* of the archwire showed significant differences among all samples. There was a high positive correlation between the reflectance and L^*. There were statistically significant positive correlations between the layperson and orthodontist groups, between the VAS score and reflectivity, and between VAS score and L^*.

Conclusion: Our results showed that as the lightness and reflectance of the brackets and archwires increased, the subjective evaluation concerning their esthetic value was higher.

Clinical significance: It is extremely difficult to evaluate esthetics despite the fact that patients' demands for esthetics have been increasing in recent years. If a method for evaluating esthetics is established, it should help in the development and selection of esthetic devices. The results of this study will facilitate the development of future study designs.

Keywords: Esthetics; Orthodontic appliances; Orthodontic archwire; Orthodontic bracket Spectrophotometry..

Frameless stereotactic brain biopsy (FSB) with navigation system has been widely used. We reported preliminary experience of FSB with intraoperative computed tomography (iCT) and examined the usefulness of this novel adjuvant technique and real target registration error (rTRE) of FSB. The FSB with 5-aminolevulinic acid (5-ALA) and iCT was performed on 10 patients. The gadolinium-enhanced lesions on magnetic resonance image were defined as the biopsy target. In the procedure, iCTs were scanned twice, for autoregistration of the navigation system and for confirmation of the position of the actual inserted biopsy needle. The red fluorescence of the samples was observed under excitation with violet-blue light through a low-cut filter of neurosurgical microscope. The distance between the planned target and the tip of the biopsy needle in the image of iCT was calculated in a workstation for the assessment of rTRE. The median volume of the target was 12.13 mL (0.06-39.15 mL). We performed the surgical procedure in a prone position in four patients. None to faint 5-ALA-induced fluorescence was observed in six samples. There existed no sampling errors. The mean target distance between the planned and real targets of the mean rTRE of FSB was 2.7 ± 0.56 mm. The real TRE of FSB was first reported and was larger than the reported rTRE exactly calculated from the fiducial registration error. iCT guarantees accurate tumor sampling with autoregistration regardless of the surgical position and prevents inaccurate biopsy to occur even with ALA fluorescence assistance.

Keywords: 5-aminolevulinic acid; frameless stereotactic biopsy; intraoperative computed tomography; navigation system; target registration error.

Type 2 diabetes mellitus (T2DM)-associated mitochondrial impairment may a key factor leading to liver injury. Transient receptor potential receptor vanilloid 1 (TRPV1) regulates the energy expenditure and cholesterol metabolism in hepatocytes and protects against oxidative toxicity. Optic atrophy 1 (OPA1) is involved in the protection of TRPV1 on cardiac microvascular and lung injury. The aim of this study is to identify the role of TRPV1 in redox signals and liver protection via OPA1. TRPV1 knockout (TRPV1^-/-) mice were used. And T2DM associated liver injury was induced by high glucose and high fatty acid (HG/HF) treatment. Mechanisms were studied by TUNEL staining, transmission electron microscope (TEM) analysis, reverse transcription polymerase chain reaction (RT-PCR) and Western blotting in vivo and in vitro. We determined that HG/HF treatment increased TRPV1 expression in liver tissues and AML12 cells. The knockout of TRPV1 increased the apoptotic hepatocytes rate. The inhibition of TRPV1 by 5'-iRTX in HG/HF group elevated the reactive oxygen species (ROS) levels, whereas TRPV1 agonist capsaicin reduced ROS. Our studies also showed that the OPA1 expression was lower in livers from HG/HF treated mice than the control, and genetic ablation of TRPV1 decreased OPA1 expression to a greater extent than the HG/HF mice. The protective effects of TRPV1 on mitochondrial were blocked by OPA1 siRNA. In conclusion, our study showed that the identified regulation of TRPV1 to OPA1 has important implication to the pathogenesis of T2DM-associated liver injury. Targeting the action of TRPV1 and OPA1 presents a potential therapeutic intervention.

Keywords: OPA1; TRPV1; mitochondria; type 2 diabetes mellitus.

High-intensity exercise and competition are associated with depressed immune function. Young horses, which participate in high-intensity exercise and competitions, are at increased risk for the development of infectious disease due to depression of immune function. The effects of branched-chain amino acid (BCAA) supplementation on the immune status of young racing horses were evaluated, determining whether BCAA might help to avoid or reduce immune suppression during exercise and competitions. Twenty horses (10 male and 10 female) were treated with BCAA supplementation; another twenty untreated horses (10 male and 10 female) constituted control group. Peripheral blood was collected from each animal and evaluated for lymphocyte subsets, phagocytosis analysis of monocytes and granulocytes, lymphocyte proliferative response, and expression of cytokine-encoding messenger ribonucleic acids (mRNAs). The numbers of CD4⁺, CD8⁺, and major histocompatibility complex (MHC) class II⁺ cells in females of the treated group were significantly higher than those in females of the control group. The lymphocyte proliferative response in female of the treated group also was significantly higher than that in females of the control group. In addition, expression of mRNAs encoding interleukin-1β (IL-1β) and interferon-γ (IFN-γ) in females of the treated group was significantly higher than that in females of the control group. There were no significant differences between males of the treated and control groups. The results of this study indicated the positive effects of BCAA supplementation in counteracting immunosuppression in young female racing horses during and following high-intensity exercise.

Keywords: branched-chain amino acid; immune status; young racing horse.

Akabane virus (AKAV), belonging to the genus Orthobunyavirus and family Peribunyaviridae, causes reproductive and congenital abnormalities in ruminants. Its envelope glycoprotein Gc is a neutralizing antigen, on which at least five distinct antigenic regions have been identified. We attempted to identify the domains using truncated recombinant AKAV Gc proteins expressed in Escherichia coli and monoclonal antibodies (mAbs) with AKAV-neutralizing activity. Dot blot analysis revealed that amino acid positions 1-97 and 189-397 (Gc_1-97 and Gc_189-397) in the truncated recombinant proteins reacted with the mAbs. Additionally, AKAV was neutralized by sera from mice immunized with these recombinant proteins. The results suggested that the two domains contain neutralizing epitopes and could be potential subunit vaccines against AKAV.

Keywords: Akabane virus; envelope glycoprotein Gc; neutralizing antibody; neutralizing domain; subunit vaccine.