RESUMEN
Background: Mycophenolate dose reduction (MDR) is associated with acute rejection and transplant failure in kidney transplant recipients (KTRs). The optimal dose to prevent rejection and reduce complications remains poorly defined in tacrolimus-based regimens. Methods: We assessed adult KTRs from 2005 to 2017 initiated on mycophenolate mofetil 2 g/d, tacrolimus, and prednisolone from the Australia and New Zealand Dialysis and Transplant Registry. KTRs with rejection within the first 30 d posttransplant were excluded. The primary outcome was time to first rejection between 30 d and 2 y posttransplant. Mycophenolate dose was modeled as a time-varying covariate using Cox proportional hazards regression. Secondary outcomes included assessment of early MDR to <1.5 g/d within the first 6 mo posttransplant and subsequent patient and death-censored graft survival. Results: In the primary analysis, 3590 KTRs were included. Compared with mycophenolate dose of ≥2 g/d, both 1.0-<1.5 and <1 g/d were associated with an increased risk of rejection during the 2 y posttransplant (hazard ratio [HR] 1.67; 95% confidence interval [CI], 1.29-2.16; Pâ <â 0.001 and HR 2.06; 95% CI, 1.36-3.13; Pâ =â 0.001, respectively) but not 1.5-<2 g/d (HR 1.20; 95% CI, 0.94-1.53; Pâ =â 0.14). Early MDR to <1.5 g/d occurred in 45.3% of KTRs and was an independent risk factor for death-censored graft failure (HR 1.32; 95% CI, 1.05-1.66; Pâ =â 0.016) but not death (HR 1.18; 95% CI, 0.97-1.44; Pâ =â 0.10), during a median follow-up of 5.0 (interquartile range, 2.6-8.5) y. Conclusions: Early MDR was a risk factor for subsequent rejection and graft failure in KTRs receiving contemporary tacrolimus-based regimens.
RESUMEN
T cell immunoglobulin and ITIM domain (TIGIT) is an immune checkpoint molecule that suppresses T cell activation and promotes an immunosuppressive environment to suppress autoimmune diseases. However, the impact of a TIGIT agonist as a treatment for ocular autoimmune disease has not been investigated. We examined TIGIT expression on Th17 and Treg cells, the role of TIGIT on experimental autoimmune uveitis (EAU) and Th17 cells, and the impact of Treg generation following TIGIT stimulation. TIGIT stimulation at the onset of clinical symptoms reduced the severity of uveitis and suppressed infiltration of Th17 cells into the eye. Further, Tregs from mice treated with the TIGIT agonist were capable of suppressing EAU in recipient mice. This report demonstrates that stimulation of TIGIT at onset of disease suppresses symptoms and allows for induction of regulatory immunity that provides resistance to uveitis.
RESUMEN
Covering: 1998 up to the end of 2023Since its initial disclosure in 1951, the Kornblum DeLaMare rearrangement has proved an important synthetic transformation and has been widely adopted as a biomimetic step in natural product synthesis. Utilising the base catalysed decomposition of alkyl peroxides to yield a ketone and alcohol has found use in many syntheses as well as a key strategic step, including the unmasking of furans, as a biomimetic synthetic tool, and the use of the rearrangement to install oxygen enantioselectively. Since ca. 1998, its impact as a synthetic transformation has grown significantly, especially given the frequency of use in natural product syntheses, therefore this 25 year time period will be the focus of the review.
Asunto(s)
Productos Biológicos , Técnicas de Química Sintética , Productos Biológicos/síntesis química , Productos Biológicos/química , Catálisis , Furanos/síntesis química , Furanos/química , Cetonas/química , Cetonas/síntesis química , Estructura Molecular , Estereoisomerismo , Técnicas de Química Sintética/historia , Técnicas de Química Sintética/métodos , Historia del Siglo XX , Historia del Siglo XXIRESUMEN
BACKGROUND: Patients with obesity often report esophageal symptoms, with abnormal reflux and esophageal motility suggested as potential mechanisms. However, prior studies showed varying results, often limited by study design/size and esophageal function/symptom measures utilized. We aimed to examine the relationship between obesity and objective esophageal function testing and patient-reported outcomes, utilizing prospective symptom, manometric and reflux monitoring data with impedance. METHODS: Adults referred for high-resolution impedance-manometry (HRiM) and multichannel intraluminal impedance-pH monitoring (MII-pH) to evaluate esophageal symptoms were enrolled. Validated symptom and health-related quality of life (HR-QOL) instruments were prospectively collected: GERDQ, reflux symptoms index (RSI), dominant symptom intensity (DSI, multiplied 5-point Likert scales for symptom frequency/severity), global symptom severity (GSS, 100-point visual analog scale), and Short Form-12 (SF-12) for HR-QOL. Esophageal function testing measures were compared across body mass index (BMI) categories and correlated with patient-reported outcomes. KEY RESULTS: Seven hundred and fifty four patients were included (Normal:281/Overweight:253/Class I obesity:137/Class II/III obesity:83). Reflux burden measures on MII-pH (acid exposure time, total reflux episodes, bolus exposure time), conclusive pathologic reflux (Lyon), and hiatal hernia were increased in higher obesity classes compared to normal BMI. Class II/III obesity was associated with more normal/hypercontractile swallows, less ineffective swallows, and better bolus transit on HRiM. BMI correlated positively with GERDQ/RSI/DSI/GSS, and negatively with physical component score (SF-12). Esophageal symptom severity and HR-QOL correlated strongly with MII-pH findings, but not HRiM measures. CONCLUSIONS/INFERENCES: Obesity is associated with increased esophageal symptom burden and worse physical HR-QOL, which correlate with higher acid/bolus reflux burden but not altered esophageal motility/transit/contractile reserve.
Asunto(s)
Reflujo Gastroesofágico , Calidad de Vida , Adulto , Humanos , Estudios Prospectivos , Monitorización del pH Esofágico , Reflujo Gastroesofágico/complicaciones , Reflujo Gastroesofágico/diagnóstico , Manometría/métodos , Obesidad/complicaciones , Impedancia EléctricaRESUMEN
BACKGROUND: High-stakes assessments are often used as a 'gate-keeper' activity for entry into the health professions by ensuring that the minimum core competency thresholds of the profession are met. The aim of the study was to explore if common areas of underperformance existed in international candidates assessed with a high-stakes clinical-based simulation assessment for entry into the physiotherapy profession in Australia. METHODS: A retrospective mixed methods analysis of the clinical assessments completed by international candidates over a one-month period in 2021 that were deemed as not meeting competency. The clinical assessments were completed in one of the three practice areas: cardiorespiratory, musculoskeletal, or neurological rehabilitation. Each assessment was scored by two independent assessors, who discussed the performance and then completed a moderated assessment form. The assessment form used to score competency included seven domains such as initial assessment, effective treatment, communication skills, and risk management. RESULTS: Fifty-one clinical assessments graded as not competent were analysed. Across the practice areas, a high failure rate was found in domains related to interpreting assessment findings and developing a treatment plan. This trend was also observed in the qualitative data, suggesting candidates struggled to meet competency in areas of planning and prioritisation, interpretation and implementation of the information gathered, and selection and evaluation of effective treatment. CONCLUSION: These findings align with published data on the underperformance of Australian physiotherapy students in clinical placement settings, suggesting these issues are not specific to high stakes assessment of overseas physiotherapists, and that education needs to focus on improving these skills within the profession at all levels. With the identified areas of underperformance aligning with the ability to use higher order thinking and skills integral to clinical reasoning, improvements in the education and implementation of clinical reasoning may be a place to start.
Asunto(s)
Medicina , Humanos , Estudios Retrospectivos , Australia , Modalidades de Fisioterapia , Empleos en SaludRESUMEN
AIMS: To describe the development of the Physical Symptom Scale-8 (PSS-8) and to examine its psychometric properties and use in temporomandibular disorder (TMD)-related assessment and research. METHODS: An online survey comprising demographic variables, the DC/TMD pain screener (TPS), Short-Form Fonseca Anamnestic Index (SFAI), PSS-8, PHQ-15, and Depression, Anxiety, and Stress Scale-21 (DASS-21) was administered to young adults attending a technical college. The PSS-8 adopted the Somatic Symptom Scale-8 (SSS-8) items but maintained the 3-point response scale and 4-week time frame of the PHQ-15. Internal consistency and reliability of the PSS-8 were determined by its Cronbach α value. Known-groups and concurrent/convergent validity were examined using Mann-Whitney U test and Spearman correlation (α = .05), respectively. RESULTS: Responses from 400 participants (mean age 18.8 ± 1.5 years; 52.3% women) were evaluated. Pain-related (WPT) and all (WAT) TMDs were present in 8.5% and 17.3% of the sample, respectively. The PSS-8 exhibited good internal consistency (α = 0.82) and sound known-groups validity, with the WPT/WAT groups having significantly higher PSS-8 scores than those without TMDs. Good concurrent and convergent validity were also observed, with moderate to strong correlations with the PHQ-15 (rs = 0.97) and DASS-21 scores (rs = 0.48 to 0.60). Correlations with the TPS and SFAI scores were weaker (rs = 0.28 to 0.34). CONCLUSION: The PSS-8 presented good psychometric properties and performed similarly to the PHQ-15. It holds promise as the "de facto" shortened version of the PHQ-15 for TMDs and related work.
Asunto(s)
Ansiedad , Trastornos de la Articulación Temporomandibular , Adulto Joven , Humanos , Femenino , Adolescente , Adulto , Masculino , Psicometría , Reproducibilidad de los Resultados , Ansiedad/diagnóstico , Dolor , Encuestas y Cuestionarios , Trastornos de la Articulación Temporomandibular/diagnósticoRESUMEN
Myeloma cast nephropathy (MCN) has historically been associated with poor kidney outcomes. We aimed to evaluate the kidney outcomes and identify prognostic factors of myeloma-associated acute kidney injury (M-AKI) in the contemporary era of anti-plasma cell therapy. Patients who received anti-myeloma therapy with M-AKI (January 2012 to June 2020) from a single centre were identified from electronic medical records. Diagnosis of MCN was either biopsy confirmed (BC) or clinically suspected (CS), the latter defined as acute kidney injury with reduced estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2 and involved serum free light chains (iSFLC) >500 mg/L at diagnosis. Twenty-six patients with M-AKI were identified (BC: n = 13, CS: n = 13). Median eGFR at diagnosis was 12 (interquartile range 6-20) mL/min/1.73 m2 . All six dialysis-requiring patients achieved dialysis independence after 71 (43-208) days. The best-achieved eGFR was 47 (32-67) mL/min/1.73 m2 after 120 (63-167) days post-treatment, which was maintained at 47 (33-66) mL/min/1.73 m2 12 months post-treatment. Patients with best-achieved eGFR above the median were more likely to have achieved an iSFLC of <20 mg/L (above median group 62% versus below median group 0%; p < .001) and lower best post-treatment iSFLC (20 (12-90) versus 67 (29-146) mg/L; p < .05). Best-achieved iSFLC was a prognostic factor for superior eGFR following treatment for M-AKI. Despite low eGFR at diagnosis, contemporary anti-myeloma therapy can achieve significant recovery of kidney function.
Asunto(s)
Lesión Renal Aguda , Mieloma Múltiple , Humanos , Pronóstico , Diálisis Renal , Riñón , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/etiología , Lesión Renal Aguda/terapia , Mieloma Múltiple/complicaciones , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/terapia , Tasa de Filtración Glomerular , Estudios RetrospectivosRESUMEN
PURPOSE: This study aimed to establish the inter-relationships between Temporomandibular disorders (TMDs), otologic, pain, and psychological comorbidities in Asian youths. METHODS: Youths, aged 17 to 24 years old, were enrolled from a local polytechnic and an electronic survey encompassing demographic variables, the DC/TMD TMD pain screener (TPS), Short-form Fonseca Anamnestic Index (SFAI), modified Maciel's Otologic/Pain Symptom Inventory, and Patient Health Questionnaire-4 was administered. Participants were subsequently categorized into "no TMD pain (NP)" and "with TMD pain (WP)" in addition to "no TMDs (NT)" and "with any TMDs (WT)" groups. Data were evaluated with the Chi-square test, non-parametric, and logistic regression analyses (α = 0.05). RESULTS: Among the 198 participants (mean age 18.8 ± 1.7 years), 11.1% had painful TMDs and 18.2% experienced TMD pain and/or dysfunction. Significant differences in total-otologic symptom (total-OS), vertigo, and dizziness plus otalgia, tinnitus, and hearing loss scores were observed between the WP-NP and WT-NT groups correspondingly. While total-comorbid pain (total-CP) and psychological distress (total-PD) scores varied substantially between the WT-NT group, only a significant difference in total-PD scores was discerned between the WP-NP group. Total-OS scores were moderately correlated to TPS/SFAI, total-CP, total-PD scores. and psychological distress was a risk factor for painful TMDs. CONCLUSION: Otologic and pain comorbidities were prevalent among Asian youths with TMDs and appear to be interrelated. The complex interaction of TMDs with otological, pain, and psychological comorbidities must be considered when caring for youths with multiple somatic complaints. Int J Prosthodont 2023. doi: 10.11607/ijp.8451.
RESUMEN
BACKGROUND: Temporomandibular disorders (TMDs) are common and affect individuals negatively. OBJECTIVES: This study investigated the inter-relationship of painful TMDs with bodily pain, psychological well-being and distress in young people from a Confucian-heritage culture (CHC). METHODS: Adolescents/young adults were recruited from a polytechnic in Singapore. While the presence/severity of painful TMDs and bodily pain were established with the DC/TMD Pain Screener (TPS) and Maciel's Pain Inventory, psychological well-being and distress were evaluated with the Scales of Psychological Well-being-18 (SPWB-18) and Patient Health Questionnaire-4 (PHQ-4). Statistical explorations were conducted using chi-square/Mann-Whitney U tests, Spearman's correlation and logistic regression analyses (α = .05). RESULTS: Among the 225 participants (mean age 20.1 ± 3.9 years) examined, 11.6% had painful TMDs and 68.9% experienced multisite bodily pain. Though painful TMDs were accompanied by a higher occurrence of multisite bodily pain, the overall/discrete number of bodily pain sites did not differ substantially between the 'no TMD pain' (NT) and 'with TMD pain' (WT) groups. Besides ear pain, differences in overall/discrete bodily pain scores were also insignificant. However, significant differences in environmental mastery, overall psychological distress, depression and anxiety subscale scores were discerned between the NT and WT groups. Psychological well-being and distress were moderately and negatively correlated (rs = -.56). Multivariate analysis indicated that ear pain and psychological distress increased the prospect of painful TMDs. CONCLUSION: The prevalence of multi-site bodily pain was high in young people from CHCs irrespective of the painful TMDs' presence of painful TMDs. Enhancing environmental mastery and relieving depression/anxiety may help manage TMD pain.
Asunto(s)
Bienestar Psicológico , Trastornos de la Articulación Temporomandibular , Adulto Joven , Adolescente , Humanos , Adulto , Dolor , Trastornos de la Articulación Temporomandibular/complicaciones , Trastornos de la Articulación Temporomandibular/epidemiología , Ansiedad , PrevalenciaRESUMEN
The proper function of regulatory T cells (Tregs) to suppress inflammation requires homing to the correct tissue site. Resolution of autoimmune uveitis generates distinct programmed death receptor 1 (PD-1+) and T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains (TIGIT+) Tregs in an adenosine 2A receptor (A2Ar)-dependent manner found in the spleen. Where and how these Tregs migrate from the spleen to prevent uveitis is not known. In this work, we show that A2Ar-dependent Tregs migrated to the eye and secondary lymphoid tissue and expressed chemokine receptor (CCR)6 and CCR7. Suppression of autoimmune uveitis required CCR6 and CCR7 expression for TIGIT+ Tregs but not PD-1+ Tregs. Moreover, stimulation of A2Ar on T cells from patients showed a decreased capacity to induce TIGIT+ Tregs that expressed CCR6 or CCR7, and PD-1+ Treg that expressed CCR6. This work provides a mechanistic understanding of the homing requirements of each of these Treg populations. Importantly, this work is clinically relevant because patients with chronic autoimmune uveitis are unable to induce the Treg populations identified in mice that home to the target tissue.
Asunto(s)
Enfermedades Autoinmunes , Linfocitos T Reguladores , Uveítis , Animales , Ratones , Inflamación/metabolismo , Receptores CCR7/metabolismo , Receptores Inmunológicos/genética , Receptores Inmunológicos/metabolismo , Uveítis/metabolismo , Enfermedades Autoinmunes/metabolismo , Receptor de Adenosina A2A/metabolismoRESUMEN
Ocular immune privilege is a phenomenon described by Peter Medawar in relation to the indefinite survival of the placement of foreign tissue grafts into the eye. Several mechanisms have been described that contribute to ocular immune privilege, such as a blood-ocular barrier and lack of lymphatics in the eye, the production of immune-suppressing molecules inside the ocular microenvironment, and the induction of systemic regulatory immunity against antigens found in the eye. Because ocular immune privilege is not absolute, failure of it can result in uveitis. Uveitis is a group of inflammatory disorders that can lead to vision loss if not treated properly. The current uveitis treatments involve the use of immunosuppressive and anti-inflammatory medications. Researching mechanisms of ocular immune privilege and the development of novel treatments for uveitis is ongoing. This review discusses mechanisms of ocular immune privilege, followed by an overview of uveitis treatments and ongoing clinical trials.
Asunto(s)
Ojo , Uveítis , Humanos , Uveítis/tratamiento farmacológico , AntígenosRESUMEN
OBJECTIVE: The reliability and dimensionality of the Depression Anxiety Stress Scale-21 (DASS-21) were explored in adolescents/young adults with temporomandibular disorders (TMDs). METHODS: TMD presence was established with the Fonseca Anamnestic Index. Reliability of the DASS-21 for participants with (WT) and without (NT) TMDs was assessed by the Cronbach alpha test, while dimensionality was examined using exploratory factor analysis. RESULTS: Data from 400 participants (mean age 18.8 ± 1.5 years; 52.2% women) comprising 47.0% with and 53.0% without TMDs were evaluated. Total-DASS and the 3 subscales showed acceptable to high internal consistencies for the WT and NT groups, with alphas of 0.78-0.94 and 0.66-0.92, respectively. Although 3 factors contributed to about half the variance for both groups, scalar and item discrepancies in the primary anxiety-stress factor existed. CONCLUSION: The DASS-21 has good reliability but may comprise only 2 dimensions, specifically anxiety-stress and depression, instead of the 3 originally asserted.
RESUMEN
Kidney transplant recipients undergo lifelong monitoring of allograft function and evaluation for transplant complications. The current monitoring paradigm utilizes blood, urine, and tissue markers that are insensitive, nonspecific, or invasive to obtain. As a result, problems are detected late, after significant damage has accrued, and often beyond the time at which complete resolution is possible. Indeed, most kidney transplants eventually fail, usually because of chronic rejection and other undetected injury. There is a clear need for a transplant-specific biomarker that enables a proactive approach to monitoring via early detection of reversible pathology. A biomarker that supports timely and personalized treatment would assist in achieving the ultimate goal of improving allograft survival and limiting therapeutic toxicity to the recipient. Donor-derived cell-free DNA (ddcfDNA) has been proposed as one such transplant biomarker. Although the test is presently utilized most in the United States, it is conceivable that its use will become more widespread. This review covers aspects of ddcfDNA that support informed use of the test by general nephrologists, including the basic biology of ddcfDNA, methodological nuances of testing, and general recommendations for use in the kidney transplant population. Clinical contexts are used to illustrate evidence-supported interpretation of ddcfDNA results and subsequent management. Finally, knowledge gaps and areas for further study are discussed.
Asunto(s)
Ácidos Nucleicos Libres de Células , Trasplante de Riñón , Humanos , Trasplante de Riñón/efectos adversos , Rechazo de Injerto/diagnóstico , Rechazo de Injerto/prevención & control , Rechazo de Injerto/etiología , Donantes de Tejidos , BiomarcadoresRESUMEN
Amyloidosis is a collection of diseases caused by the misfolding of proteins that aggregate into insoluble amyloid fibrils and deposit in tissues. While these fibrils may aggregate to form insignificant localised deposits, they can also accumulate in multiple organs to the extent that amyloidosis can be an immediately life-threatening disease, requiring urgent treatment. Recent advances in diagnostic techniques and therapies are dramatically changing the disease landscape and patient prognosis. Delays in diagnosis and treatment remain the greatest challenge, necessitating physician awareness of the common clinical presentations that suggest amyloidosis. The most common types are transthyretin (ATTR) amyloidosis followed by immunoglobulin light-chain (AL) amyloidosis. While systemic AL amyloidosis was previously considered a death sentence with no effective therapies, significant improvement in patient survival has occurred over the past 2 decades, driven by greater understanding of the disease process, risk-adapted adoption of myeloma therapies such as proteosome inhibitors (bortezomib) and monoclonal antibodies (daratumumab) and improved supportive care. ATTR amyloidosis is an underdiagnosed cause of heart failure. Technetium scintigraphy has made noninvasive diagnosis much easier, and ATTR is now recognised as the most common type of amyloidosis because of the increased identification of age-related ATTR. There are emerging ATTR treatments that slow disease progression, decrease patient hospitalisations and improve patient quality of life and survival. This review aims to update physicians on recent developments in amyloidosis diagnosis and management and to provide a diagnostic and treatment framework to improve the management of patients with all forms of amyloidosis.
Asunto(s)
Amiloidosis , Cardiomiopatías , Insuficiencia Cardíaca , Humanos , Calidad de Vida , Amiloidosis/diagnóstico , Amiloidosis/terapia , Amiloidosis/complicaciones , Insuficiencia Cardíaca/diagnóstico , Pronóstico , Bortezomib/uso terapéutico , Cardiomiopatías/diagnósticoRESUMEN
We report the development of a single-pass electrochemical Birch reduction carried out in a small footprint electrochemical Taylor vortex reactor with projected productivities of >80 g day-1 (based on 32.2 mmol h-1), using a modified version of our previously reported reactor [Org. Process Res. Dev. 2021, 25, 7, 1619-1627], consisting of a static outer electrode and a rapidly rotating cylindrical inner electrode. In this study, we used an aluminum tube as the sacrificial outer electrode and stainless steel as the rotating inner electrode. We have established the viability of using a sacrificial aluminum anode for the electrochemical reduction of naphthalene, and by varying the current, we can switch between high selectivity (>90%) for either the single ring reduction or double ring reduction with >80 g day-1 projected productivity for either product. The concentration of LiBr in solution changes the fluid dynamics of the reaction mixture investigated by computational fluid dynamics, and this affects equilibration time, monitored using Fourier transform infrared spectroscopy. We show that the concentrations of electrolyte (LiBr) and proton source (dimethylurea) can be reduced while maintaining high reaction efficiency. We also report the reduction of 1-aminonaphthalene, which has been used as a precursor to the API Ropinirole. We find that our methodology produces the corresponding dihydronaphthalene with excellent selectivity and 88% isolated yield in an uninterrupted run of >8 h with a projected productivity of >100 g day-1.
RESUMEN
OBJECTIVES: This study estimated the prevalence of dental fear/anxiety (DFA) in Southeast Asian youths and established their dental environment and practitioner preferences. METHODS: A convenience sample of youths were enrolled from a local polytechnic. The Index of Dental Anxiety and Fear (IDAF-4C) was used to ascertain the presence and severity of DFA. Socio-demographic and IDAF-4C data, along with participants' dental environment and practitioner partialities were gathered electronically. Statistical evaluations were performed with Kruskal-Wallis and Chi-square tests (α = 0.05). RESULTS: Data from a total of 215 participants were appraised. The mean age of the study sample was 18.9 ± 2.0 years (87.4% women). Of these, 12.6% had moderate-to-high DFA and 6.0% had high-to-extreme DFA. As a group, Southeast Asian youths generally liked dental clinics with adorned walls, cooler temperatures, magazines/books, background music and audio-visual devices. In addition, they favoured female practitioners who are younger (≤45 years old), friendly, talkative and maintain a professional relationship. However, those with high-to-extreme DFA preferred a warmer clinic environment and to have an informal relationship with their dental practitioners (p = 0.01). CONCLUSIONS: The prevalence of moderate-to-extreme DFA in Southeast Asian youths was 18.6%. Individuals with high-to-extreme DFA may have disparate dental environment and practitioner preferences compared to those with no-to-moderate DFA.
Asunto(s)
Ansiedad al Tratamiento Odontológico , Higienistas Dentales , Odontólogos , Miedo , Adolescente , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Ansiedad al Tratamiento Odontológico/epidemiología , Rol Profesional , Psicometría , Encuestas y CuestionariosRESUMEN
The cell wall is a critical extracellular barrier for bacteria and many other organisms. In bacteria, this structural layer consists of peptidoglycan, which maintains cell shape and structural integrity and provides a scaffold for displaying various protein factors. To attach proteins to the cell wall, Gram-positive bacteria utilize sortase enzymes, which are cysteine transpeptidases that recognize and cleave a specific sorting signal, followed by ligation of the sorting signal-containing protein to the peptidoglycan precursor lipid II (LII). This mechanism is the subject of considerable interest as a target for therapeutic intervention and as a tool for protein engineering, where sortases have enabled sortase-mediated ligation or sortagging strategies. Despite these uses, there remains an incomplete understanding of the stereochemistry of substrate recognition and ligation product formation. Here, we solved the first structures of sortase A from Streptococcus pyogenes bound to two substrate sequences, LPATA and LPATS. In addition, we synthesized a mimetic of the product of sortase-mediated ligation involving LII (LPAT-LII) and solved the complex structure in two ligand conformations. These structures were further used as the basis for molecular dynamics simulations to probe sortase A-ligand dynamics and to construct a model of the acyl-enzyme intermediate, thus providing a structural view of multiple key states in the catalytic mechanism. Overall, this structural information provides new insights into the recognition of the sortase substrate motif and LII ligation partner and will support the continued development of sortases for protein engineering applications.
Asunto(s)
Aminoaciltransferasas , Aminoaciltransferasas/química , Aminoaciltransferasas/metabolismo , Proteínas Bacterianas/química , Proteínas Bacterianas/metabolismo , Ligandos , Peptidoglicano , Streptococcus pyogenes/enzimologíaRESUMEN
OBJECTIVE: The relationships between temporomandibular disorders (TMDs) and negative affectivity/emotions across cultures and the emotional predictors for TMDs in Southeast Asian youths were investigated. METHODS: The presence of TMDs and negative affectivity/emotions were determined with the Fonseca Anamnestic Index (FAI) and Depression, Anxiety, Stress Scales-21 (DASS-21). Statistical evaluations were done with non-parametric and logistic regression analyses (α. RESULTS: The total sample comprised 400 Singaporean and 501 Indonesian youths (mean age 19.30 ± 1.48 years; 65.0% women) of whom 47.0% and 59.3% had mild-to-severe TMDs, respectively. For both cultures, participants with TMDs had significantly greater negative affectivity, depression, anxiety, and stress than those with no TMDs. Indonesian youths also presented higher levels of emotional distress than their Singaporean counterparts. Correlations between FAI and anxiety/stress scores were moderately strong. CONCLUSION: Cultural variations can influence the expression of TMDs and emotional distress. Being female and anxious increased the risk of TMDs.
RESUMEN
BACKGROUND: Although evidence exists for the efficacy of high-fidelity simulation as an educational tool, there is limited evidence for its application in high-stakes professional threshold competency assessment. An alternative model of simulation-based assessment was developed by the Australian Physiotherapy Council (APC), using purpose-written standardised patients, mapped to the appropriate threshold level. The aim of this two-phase study was to investigate whether simulation-based clinical assessments resulted in equivalent outcomes to standard, real-life assessments for overseas-trained physiotherapists seeking registration to practice in Australia. METHODS: A randomised crossover trial comparing simulation-based assessment to real-life assessment was completed. Participants were internationally trained physiotherapists applying for registration to practice in Australia, voluntarily recruited from the Australian Physiotherapy Council (APC) assessment waiting list: study 1 n = 25, study 2 n = 144. Study 1 participants completed usual APC real-life assessments in 3 practice areas, completed on different days at APC partner healthcare facilities. Participants also underwent 3 practice area-matched simulation-based assessments, completed on the same day at purpose-designed simulation facilities. Study 2 participants completed 3 simulation-based assessments and 1 real-life assessment that was randomly allocated for order and practice area. Assessment of competency followed the standard APC procedure of 90-minute examinations using The Moderated Assessment Form (MAF). RESULTS: The overall pass rate was higher for real-life assessments in both studies: study 1, 50% versus 42.7%; study 2, 55.6% versus 44.4%. Chi-square analysis showed a high to moderate level of exact matching of pass/fail grades across all assessments: study 1, 73.4% (p < 0.001); study 2, 58.3% (p = 0.027). Binary logistic regression showed that the best predictors of real-life pass/fail grade were simulation-based MAF pass/fail grade (study 1, OR 7.86 p < 0.001; study 2, OR 2.037, p = 0.038) and simulation-based total MAF score (study 1, OR 1.464 p < 0.001; study 2, OR 1.234, p = 0.001). CONCLUSION: Simulation-based assessment is a significant predictor of clinical performance and can be used to successfully identify high stakes threshold competence to practice physiotherapy in Australia.
RESUMEN
OBJECTIVE: To investigate the presence/severity of TMDs among Asian youths and examine the associations between TMD severity, otologic, and concomitant pain symptoms. METHODS: Youths (17-24 years old) were recruited from a local polytechnic. The presence/severity of TMDs was determined with the Fonseca Anamnestic Index (FAI), while otologic/concomitant pain symptoms were appraised with the Maciel's Symptoms Checklist (MSC). Demographic, FAI, and MSC data were evaluated using Kruskal Wallis, chi-square, and relevant post-hoc tests (α = 0.05). RESULTS: Among the participants (n = 200) enrolled, 40.5% had no TMD, whereas mild, moderate, and severe TMD were present in 43.5%, 12.5%, and 3.5%, respectively. Participants with moderate/severe TMDs had significantly more otalgia, tinnitus, vertigo, dizziness, ear pruritus, hearing loss, ear fullness, headache, eye, neck, and back pain than those with no TMDs (p < 0.001). CONCLUSION: Otologic and concomitant pain symptoms were associated with TMDs and appear to increase with progressive TMD severity.