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INTRODUCTION: Essential tremor (ET) patients may exhibit a variety of non-motor features, including cognitive decline and depressive symptoms. Studies of several neurodegenerative diseases link depression to cognitive decline, suggesting depression is an early marker of dementia. We examined whether baseline depressive symptoms predict incident dementia in elders with ET. METHODS: Hundred and forty-one ET cases aged 70 years or older at baseline, enrolled in a prospective study of cognitive performance, took part in evaluations at baseline and at 18, 36, 54, and 72 months. Participants completed the Geriatric Depression Scale (GDS), a 30-item self-report measure of depressive symptoms, and a battery of neuropsychological tests and functional assessments, from which we derived cognitive diagnoses at each evaluation. Cox proportional hazards regression equations determined incident dementia risk based on participants' baseline depression scores. RESULTS: Mean baseline age was 81.5 ± 6.7 years. Higher baseline GDS scores were associated with increased risk of dementia in an unadjusted model (hazards ratio [HR] = 1.11, 95% confidence interval [CI] = 1.02-1.20, p = 0.01) and after controlling for baseline age, education, number of medications, and tremor onset age (HR = 1.13, 95% CI = 1.02-1.25, p = 0.02). CONCLUSION: Baseline depression scores predicted incident dementia in elders with ET. With each one-point increase in baseline depression score, there was a 13% increase in incident dementia risk. Given the published data that reported depression may be twice as high in elders with ET compared to controls, this association is particularly worrisome in the ET population.
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INTRODUCTION: Sleep disturbances have been associated with essential tremor (ET). However, their pathophysiological underpinnings remain unknown. In this exploratory study, we examined the association between subjective sleep disturbances and the presence of Lewy pathology (LP) on postmortem brain examination in ET cases. METHODS: Fifty-two ET cases enrolled in a prospective, longitudinal study were assessed over an average period of 42 months. Cases completed the Pittsburgh Sleep Quality Index (PSQI), which yields seven component scores (e.g., sleep quality, sleep latency). For each component score, we calculated the difference between the last score and the baseline score. Brains were harvested at death. Each had a complete neuropathological assessment, including extensive α-synuclein immunostaining. We examined the associations between baseline PSQI scores and the change in PSQI scores (last - first), and LP on postmortem brain examination. RESULTS: ET cases had a mean baseline age of 87.1 ± 4.8 years. LP was observed in 12 (23.1%) of 52 cases; in 7 of these 12, LP was observed in the locus coeruleus (LC). Change in time needed to fall asleep (last - first sleep latency component score) was associated with presence of LP on postmortem brain examination - greater increase in sleep latency was associated with higher odds of LP (odds ratio = 2.98, p = 0.02). The greatest increase in sleep latency was observed in cases with LP in the LC (p = 0.04). CONCLUSION: In ET cases, increases in sleep latency over time could be a marker of underlying LP, especially in the LC.
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Encéfalo , Temblor Esencial , Trastornos del Sueño-Vigilia , Humanos , Temblor Esencial/patología , Femenino , Masculino , Trastornos del Sueño-Vigilia/patología , Trastornos del Sueño-Vigilia/epidemiología , Anciano de 80 o más Años , Estudios Longitudinales , Anciano , Encéfalo/patología , Estudios Prospectivos , Cuerpos de Lewy/patología , Estudios de Cohortes , alfa-Sinucleína/metabolismoRESUMEN
OBJECTIVE: Despite recent attention to cognitive impairment in essential tremor, few studies examine rates of conversion to diagnoses of mild cognitive impairment and dementia. Development of dementia in essential tremor is associated with loss of functional ability and a doubling of mortality rate. This prospective, longitudinal study comprehensively reports the prevalence and incidence of, and the annual rates of conversion to, mild cognitive impairment and dementia in an essential tremor cohort. METHODS: Patients underwent detailed cognitive assessments and were assigned diagnoses of normal cognition, mild cognitive impairment, or dementia. There were 222 patients at baseline (mean age = 79.3 ± 9.7 years), and 177 patients participated in follow-up evaluations at 18, 36, 54, and 72 months (mean years of observation = 5.1 ± 1.7). Data were compared to those of historical controls and Parkinson disease patients. RESULTS: The cumulative prevalence of dementia and average annual conversion rate of mild cognitive impairment to dementia were 18.5% and 12.2%, nearly three times higher than rates in the general population, and approximately one half the magnitude of those reported for Parkinson disease patients. The cumulative prevalence of mild cognitive impairment (26.6%) was almost double that of the general population, but less than that in Parkinson disease populations. INTERPRETATION: We present the most complete exposition of the longitudinal trajectory of cognitive impairment in an essential tremor cohort yet presented. The prevalence of and conversion rates to dementia in essential tremor fall between those associated with the natural course of aging and the more pronounced rates observed in Parkinson disease. ANN NEUROL 2024;95:1193-1204.
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Disfunción Cognitiva , Demencia , Progresión de la Enfermedad , Temblor Esencial , Humanos , Temblor Esencial/epidemiología , Disfunción Cognitiva/epidemiología , Femenino , Masculino , Anciano , Prevalencia , Estudios Longitudinales , Demencia/epidemiología , Anciano de 80 o más Años , Estudios Prospectivos , Estudios de CohortesRESUMEN
Background: Evaluating tremor severity is a critical component of diagnosing and clinically managing patients with essential tremor (ET). We examined the comparability of tremor severity ratings derived from two frequently used tremor rating scales: the Washington Heights-Inwood Genetic Study of Essential Tremor (WHIGET) rating scale and the Tremor Research Group Essential Tremor Rating Scale (TETRAS). Methods: A trained assistant administered and videotaped a neurological examination, including eight items assessing upper limb action tremor (arms outstretched, arms in the wingbeat position, finger-nose-finger maneuver, and drawing of Archimedes spirals). An experienced movement disorders neurologist reviewed the videos and assigned WHIGET and TETRAS ratings. We calculated associations between TETRAS and WHIGET ratings using Spearman rank order correlations. Subsequently, we collapsed these ratings into four tremor severity categories (absent, mild, moderate, severe) and then two broader tremor severity categories (absent/mild, moderate/severe). We calculated weighted Kappa coefficients to assess agreement between category assignments based on the TETRAS and the WHIGET. Results: Spearman's r' s were significant for all items (p's ≤ 0.001, mean r = 0.89). Weighted Kappa's revealed substantial to near perfect agreement for all eight items (mean k = 0.86, range = 0.64 to 1.00). Conclusion: Analyses revealed substantial strength of association and substantial to near perfect agreement between items rated with the WHIGET and TETRAS scales. These data indicated that ratings provided by each scale are highly comparable.
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Temblor Esencial , Temblor , Humanos , Temblor/diagnóstico , Temblor/genética , Temblor Esencial/diagnóstico , Washingtón , Examen Neurológico , Extremidad SuperiorRESUMEN
BACKGROUND: There is growing evidence that essential tremor (ET) patients are at high risk of cognitive impairment. Predictors of cognitive impairment have not been studied extensively. There is evidence from cross-sectional studies that sleep dysregulation is associated with cognitive dysfunction in ET, but longitudinal studies of the impact of sleep disruption on cognitive change have not been conducted. We investigated the extent to which sleep problems predict cognitive change in patients with ET. METHODS: ET cases enrolled in a prospective, longitudinal study of cognitive performance. Sleep quality was assessed using the Pittsburg Sleep Quality Index (PSQI). Cognitive abilities across five domains (memory, executive function, attention, language, and visuospatial ability), and a global cognitive score (mean of the domains) were extracted from an extensive neuropsychological assessment. Generalized estimated equations were used to examine the association between baseline sleep problems and cognitive changes over three follow-up assessments each spaced 18 months apart. RESULTS: The 188 non-demented ET cases had a mean age of 77.7 ± 9.5 years. Longer sleep latency was associated with longitudinal decline in executive function (p = 0.038), and marginally with longitudinal decline in global cognitive performance (p = 0.075). After excluding 29 cases with mild cognitive impairment, results were similar. CONCLUSION: Cognitively healthy people with ET who have longer sleep latency had greater declines in executive function during prospective follow-up. Early detection of, and possibly intervention for, abnormal sleep latency may protect against certain aspects of cognitive decline in ET patients.
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Disfunción Cognitiva , Temblor Esencial , Trastornos del Sueño-Vigilia , Humanos , Anciano , Anciano de 80 o más Años , Estudios Longitudinales , Estudios Prospectivos , Temblor Esencial/complicaciones , Temblor Esencial/psicología , Estudios Transversales , Disfunción Cognitiva/complicaciones , Cognición/fisiología , Pruebas Neuropsicológicas , Trastornos del Sueño-Vigilia/psicologíaRESUMEN
OBJECTIVE: To evaluate the benefit of anatomical muscle dissection repair for velopharyngeal insufficiency (VPI) in patients with submucous cleft palate (SMCP) with 22q11.2 deletion syndrome. DESIGN: Retrospective blinded randomised analysis of a surgeon's management over 10 years. SETTING: The study was performed at a specialised Paediatric hospital in the United Kingdom. PATIENTS: Children with SMCP and 22q11.2 deletion syndrome. INTERVENTIONS: All participants underwent radical muscle dissection veloplasty. OUTCOMES MEASURED: Pre- and post- operative measurements included severity of anatomical defect, speech samples and lateral images which were digitised, randomised then externally and blindly analysed using validated techniques. Stata software was used to perform statistical analysis. RESULTS: 57 children with 22q11.2 deletion syndrome were included in this analysis. Intra-operatively, the majority of cases were identified as SMCP Grade I anomalies. Post-operatively, a statistically significant improvement in hypernasality, resting palate length, palate length at maximum closure, palate excursion and gap size at maximum closure was observed. Secondary surgery was performed for 59% of patients by ten years. CONCLUSION: Muscle dissection repair improves hypernasality, palate closure function and the closure gap in patients with 22q11.2 deletion syndrome. Although over 50% of patients may require further surgery, muscle dissection repair should be a first step due to its utility at a younger age, when invasive investigations are impossible, its lower morbidity, speech and language benefits or altering the plans for less obstructive secondary surgery when it lead to reduced velo-pharyngeal gap and improved palate mobility even when adequate velo-pharyngeal closure was not achieved.
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Fisura del Paladar , Síndrome de DiGeorge , Enfermedades Nasales , Insuficiencia Velofaríngea , Humanos , Niño , Fisura del Paladar/cirugía , Fisura del Paladar/complicaciones , Síndrome de DiGeorge/cirugía , Habla , Estudios Retrospectivos , Insuficiencia Velofaríngea/cirugía , Insuficiencia Velofaríngea/complicaciones , Músculos , Resultado del TratamientoRESUMEN
Background: Cognitive impairment is a feature of essential tremor (ET). There are no studies of the genetic drivers of this association. We examined whether the microtubule-associated protein tau (MAPT) H1 haplotype is associated with cognitive performance in ET. Methods: ET cases genotyped for the MAPT H1 and H2 haplotypes completed a battery of neuropsychological tests at baseline and four follow-up evaluations. Chi-square, t-tests, and analyses of covariance examined associations between the presence of the MAPT H1 haplotype, cognitive diagnoses of normal, mild cognitive impairment (MCI), and dementia, and performance in specific cognitive domains. Results: We observed no evidence of cognitive differences as a function of the presence of the MAPT H1 haplotype. Specifically, cases with (n = 57) and without (n = 42) this haplotype did not differ with respect to the prevalence of diagnoses of MCI or dementia, p ≥ 0.87. Moreover, cases with vs without this haplotype did not differ in either the age or point in the disease course at which observed conversions to MCI or dementia occurred, p's ≥ 0.51. Finally, no haplotype-related differences were observed in performance in the cognitive domains of attention, executive function, language, memory, visuospatial or global ability, p's ≥ 0.21, or in changes in performance in these domains across time, p's ≥ 0.08. Discussion: The study in an ET cohort revealed no influence of MAPT haplotypes on cognitive performance. This study serves as a valuable foundation for future studies to expand our understanding of the genetic drivers of cognitive impairment in ET. Highlights: This study found no evidence of cognitive differences between individuals with and without the MAPT H1 haplotype. Our work provides a valuable foundation for future work to expand our knowledge of the genetic drivers of cognitive impairment in ET.
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Demencia , Temblor Esencial , Humanos , Estudios Longitudinales , Estudios Prospectivos , Temblor Esencial/genética , Demencia/genética , Cognición , Proteínas tau/genéticaRESUMEN
Background and Objectives: There has been a long-standing dialog as to whether essential tremor (ET) increases the risk of developing Parkinson disease (PD). While there are relevant cross-sectional data, there are almost no longitudinal prospective data. We quantified the conversion rate from ET to ETPD in a prospective longitudinal cohort study of patients with ET. We compared the observed rate with that reported in the epidemiologic literature. Methods: We enrolled patients with ET in a prospective, longitudinal study. A senior movement disorders neurologist evaluated standardized neurologic examinations every 18 months. Results: One hundred ninety-three patients with ET (mean age = 78.1 ± 9.6 years, range = 55-96) had a mean follow-up duration of 4.1 years. Seven (3.6%) converted from ET to ETPD. The incidence of PD among patients with ET was 7/792.9 person-years (py; i.e., 882.8/100,000 py). A meta-analysis of the incidence (per 100,000 py) of PD in 14 studies from 13 countries across 4 continents reported an incidence of PD = 61.21 (men, 40 years or older) and 37.55 (women, 40 years or older). The incidence/100,000 py in men peaked in the 80- to 89-year-old age group (258.47) and in women in the 80- to 89-year-old age group (103.48 py). The abovementioned published values are 3.4-23.5 times lower than the value we observed for ET. Discussion: The incidence of PD in an ET cohort is substantially higher than that reported in historical population-based control groups across numerous countries. Additional prospective longitudinal data are needed to further explore this association.
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BACKGROUND: Cosmeceutical preparations containing growth factors (GFs) are widely used for facial rejuvenation. OBJECTIVE: We performed a systematic review to assess the evidence regarding their safety and effectiveness for facial rejuvenation. METHODS: Electronic databases (Cochrane Library, EMBASE, MEDLINE, and Scopus) were searched from 2000 to October 2022 for prospective trials and case series assessing topical GF preparations for facial rejuvenation in 10 or more participants. RESULTS: Thirty-three studies, including 9 randomized controlled trials (RCTs) and 24 uncontrolled case series, representing 1180 participants receiving 23 different topical preparations containing GFs met the inclusion criteria and were included. Of the 33 studies, nine used a placebo or active control. The GF preparations were applied twice daily in all except two studies, with a mean treatment duration of 3 months. Based on the investigator's assessment, preparations containing GFs induce a modest improvement in skin texture (median < 50%), fine lines/wrinkles (median < 35%), and overall facial appearance (median < 20%) versus baseline. Participant-assessed improvement was generally higher than investigator-assessed response. Three comparative RCTs showed no statistically significant differences between treatments. Studies were limited by heterogeneity with regard to the source and number of GFs used in the preparations, information about additional ingredients, and lack of standardization in the outcome measures. The preparations were associated with a low risk of adverse events. The persistence of the clinical improvements beyond 6 months is not known. CONCLUSIONS: Administration of topical preparations containing GFs appears to be effective for facial skin rejuvenation, as demonstrated by the investigator- and participant-reported outcome measures.
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Rejuvenecimiento , Piel , Humanos , Péptidos y Proteínas de Señalización Intercelular/efectos adversosRESUMEN
Study Design: Injuries sustained in war-zones are variable and constantly developing according to the nature of the ongoing conflict. Soft tissue involvement of the extremities, head and neck often necessitates reconstructive expertise. However, current training to manage injuries in such settings is heterogenous. This study involves a systematic review. Objective: To evaluate interventions in place to train Plastic and Maxillofacial surgeons for war-zone environments so that limitations to current training can be addressed. Methods: A literature search of Medline and EMBase was performed using terms relevant to Plastic and Maxillofacial surgery training and war-zone environments. Articles that met the inclusion criteria were scored then educational interventions described in included literature were categorised according to their length, delivery style and training environment. Between-group ANOVA was performed to compare training strategies. Results: 2055 citations were identified through this literature search. Thirty-three studies were included in this analysis. The highest scoring interventions were over an extended time-frame with an action-oriented training approach, using simulation or actual patients. Core competencies addressed by these strategies included technical and non-technical skills necessary when working in war-zone type settings. Conclusions: Surgical rotations in trauma centers and areas of civil strife, together with didactic courses are valuable strategies to train surgeons for war-zones. These opportunities must be readily available globally and be targeted to the surgical needs of the local population, anticipating the types of combat injuries that often occur in these environments.
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To delineate the indications, referral sources and outcomes of radical muscle dissection palate repair in the first 4 years of life for patients with submucous cleft palate (SMCP).This study presents a retrospective analysis of a single surgeon's management.All children were treated at Great Ormond Street Hospital, United Kingdom.Twenty-three children with nonsyndromic SMCP were included in this study.All participants underwent radical muscle dissection repair before their fourth birthday.Parameters analyzed included: referral sources, indications for referral, extent of anatomical abnormality, and postoperative outcomes.Paediatricians provided the largest proportion of referrals to the cleft lip and palate clinic (39%) due to the presence of cleft lip/palate on prenatal scans or during neonatal examination. Over half (n = 12, 52%) of patients had severe anatomical anomalies being in grade IV (score 8-9), with the classical triad present to some extent in all but 2 of the patients. The main indication for surgery was nasal regurgitation of food and liquid (n = 9, 35%) followed by hypernasality (n = 6, 21%), difficulty feeding (n = 3, 8%), and severe anatomical defect (n = 2; 4%). Postoperatively, the presenting complaint improved in the majority of cases.Nonsyndromic SMCP is often missed, though may present with nasal regurgitation, feeding problems, and/or hypernasality, though may be missed in nonsyndromic children. Early radical muscle dissection repair in the first 4 years of life is safe and effective, facilitating normal speech development.
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Labio Leporino , Fisura del Paladar , Insuficiencia Velofaríngea , Recién Nacido , Humanos , Niño , Preescolar , Fisura del Paladar/cirugía , Fisura del Paladar/diagnóstico , Labio Leporino/cirugía , Estudios Retrospectivos , Músculos , Insuficiencia Velofaríngea/cirugía , Resultado del TratamientoRESUMEN
BACKGROUND: Essential tremor (ET) is a highly prevalent neurological disease. Age of onset can occur anytime between childhood and advanced age. Tremor generally starts insidiously. Age of onset is a particularly important data item in clinical and epidemiological research. In general, these data are self-reported by ET cases. A fundamental question is whether ET cases reliably report their age of onset. METHODS: In this prospective, epidemiological study of 125 ET cases, self-reported age of onset data were collected at regular 18 months intervals over four time points. RESULTS: The correlation between self-reported age of onset was high - intra-class correlation coefficient = 0.972 (95% confidence interval = 0.962-0.980, p < 0.001). However, agreement was not perfect. Approximately 20-25% of participant's reports at different time intervals differed by as much as 10 years, and approximately 10% of participant's reports differed by as much as 20 years. CONCLUSIONS: There was a robust correlation between self-reports of age of onset. Yet in a not-insignificant number of cases, there were considerable differences, some of which were substantial. These findings have broad implications for development of diagnostic algorithms, data stratification schemes, and analyses that assess correlations between biomarker data and clinical features (e.g., disease duration).
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Temblor Esencial , Humanos , Niño , Lactante , Temblor Esencial/epidemiología , Temblor Esencial/diagnóstico , Autoinforme , Edad de Inicio , Estudios Prospectivos , Reproducibilidad de los ResultadosRESUMEN
Background: The World health organization declared the coronavirus outbreak a global pandemic on March 11, 2020. Telemedicine was one of the effective tools that were implemented during this pandemic. Most Lebanese physicians have been using telemedicine to perform virtual medical services during the COVID-19 pandemic. Therefore, it is important to assess the physicians' acceptability of telemedicine and willingness to use it in routine health care settings. Objective: We developed and validated a tool based on technology acceptance model (TAM) to explore the acceptance of telemedicine use during the pandemic among Lebanese physicians. Theoretical Background: Telemedicine Acceptance Model during Pandemic (TeAM) was developed based on TAM. The model was developed considering the associations between constructs affecting the physicians' attitudes about telemedicine use. TeAM is a tool assessing telemedicine acceptance based on the TAM. It has additional constructs tackling the perceived risks of telemedicine use, the perceived need for policies, the perceived need for training, and the perceived usefulness of telemedicine during a pandemic. Methods: This cross-sectional study was conducted online through an email-based questionnaire sent to physicians enrolled in the Lebanese Order of Physicians. Results: Three hundred ninety physicians (n = 390) completed the survey. The tool was structured to test 10 hypotheses, out of which 9 were supported. The Cronbach's alpha score of each construct ranged between 0.745 and 0.905, all greater than 0.7 indicating an acceptable to excellent internal consistency. Conclusion: This study was able to validate TeAM as a reliable tool that can assess the acceptance of telemedicine among physicians. Accordingly, several determinants influencing this acceptance were identified. Practice implications include hospitals, primary health care centers, and national health care systems willing to adopt telemedicine can use TeAM to assess the physicians' willingness to accept the implementation of telemedicine in their practice.
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COVID-19 , Médicos , Telemedicina , Humanos , Pandemias , COVID-19/epidemiología , Estudios Transversales , Actitud del Personal de SaludRESUMEN
BACKGROUND: During periods of civil strife, the need for trauma care and lack of sufficient cleft surgeons causes an increase in children left untreated with cleft lip and palate deformities. During the Syrian war, some cleft care was provided through visiting charities, with surgeries performed both in Syria and neighboring countries. There is a need to increase the number of adequately trained cleft surgeons available in such regions so that care can be achieved beyond mission trips. METHODOLOGY: Cleft lip and palate repair workshops were delivered to 50 doctors in Syria. Pre-workshop, trainees received supplementary learning material. During the workshop, attendees received didactic teaching followed by 2 simulation sessions. Pre- and post-workshop, attendees completed questionnaires regarding their confidence and ability to perform cleft lip and palate repair. RESULTS: Pre-workshop, 96% of workshop attendees had never independently performed cleft lip repair while 100% of attendees had not previously performed cleft palate repair. The mean pre-workshop confidence score was 2.452. Post-workshop, the mean confidence score was 3.503. Confidence rating scores significantly improved (P < .001). CONCLUSION: The workshop delivered in Syria, together with this cleft lip and palate simulator provides an effective training tool that may support surgical training globally, particularly those in low-income countries. Further support is needed by charity organizations to ensure the continued delivery of such training.
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Background: Intimate partner violence (IPV) is a gendered form of violence that has been linked with traumatic brain injury (TBI). The prevalence of IPV in sub-Saharan Africa (SSA) is estimated to be one of the highest globally. Yet, little is known about the association between IPV and TBI in the SSA context. In this scoping review, we examine the intersection between IPV and TBI in SSA to identify gaps, as well as intervention opportunities. Methods: Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses-Extension for Scoping Review (PRISMA-ScR) guidelines to guide our analyses and reporting, we searched for published articles indexed in the four largest and most comprehensive library databases: Pubmed, Embase, Web of Science and PsychInfo. Given the increasing attention that has been placed on gender disparities and health in recent years, we focused on studies published between 2010 and 2021. Results: Our search yielded 5,947 articles and 1,258 were IPV and SSA related. Out of this, only ten examined the intersection between IPV and TBI. All focused on outcomes in female populations from South Africa (n = 5), Ghana (n = 3), Uganda (n = 1), and Cameroon (n = 1). They were a mix of qualitative studies (n = 3), neuro-imaging/biomarker studies (n = 3), case studies/reports (n = 2), quantitative surveys (n = 1) and mixed qualitative/quantitative study (n = 1). Six studies evaluated subjective reporting of IPV-induced TBI symptoms such as headaches, sleep disruptions, and ophthalmic injuries. Three examined objective assessments and included Hypothalamic-Pituitary-Adrenal (HPA) dysregulation detected by salivary cortisol levels, magnetic resonance imaging (MRI) including diffusion tensor imaging (DTI) to evaluate brain connectivity and white matter changes. One final study took a forensic anthropology lens to document an autopsy case report of IPV-induced mortality due to physical head and face trauma. Conclusion: Our findings demonstrate that both subjective and objective assessments of IPV and TBI are possible in "resource-limited" settings. The combination of these outcomes will be critical for viewing IPV through a clinical rather than a cultural lens, and for substantiating the assertion that gender, is indeed, a social determinant of brain health.
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INTRODUCTION: Low- and middle-income countries account for over 90% of burns worldwide. Though mission trips, public health interventions and educational strategies have been introduced in recent years, a disparity remains in treatment provided between high- and low -income countries. This analysis aims to review available literature pertaining to strategies for training in burns management, with a focus on those applicable to low-income countries. METHODOLOGY: Mesh terms including "burns", "burns care", "burns management", "training", "teaching" and "education" were inputted into Medline and EMBase. Studies were included on the basis that they include an educational intervention to train doctors to provide surgical burns care in low-income countries. Included literature was analysed using scoring tools then a critical appraisal was performed. RESULTS: Fourteen studies were included in this analysis. These describe e-learning (n = 1), video-based teaching (n = 1), lecture-based teaching (n = 1), simulation training (n = 8) and hospital-based training achieved through collaborative efforts between high and low-income countries such as mission trips and fellowship programmes (n = 3). The strategies described have been summarised and presented. CONCLUSION: Burns care training should be accessible at a global scale and so, involve training methods including simulation, courses and fellowship programmes that are affordable and accessible to surgeons in low-income countries.
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Quemaduras , Países en Desarrollo , Humanos , Quemaduras/cirugía , Pobreza , RentaRESUMEN
Despite rapid development and deployment of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), clinically relevant modalities to curb the pandemic by directly attacking the virus on a genetic level remain highly desirable and are urgently needed. Here we comprehensively illustrate the capacity of adeno-associated virus (AAV) vectors co-expressing a cocktail of three short hairpin RNAs (shRNAs; RNAi triggers) directed against the SARS-CoV-2 RdRp and N genes as versatile and effective antiviral agents. In cultured monkey cells and human gut organoids, our most potent vector, SAVIOR (SARS virus repressor), suppressed SARS-CoV-2 infection to background levels. Strikingly, in control experiments using single shRNAs, multiple SARS-CoV-2 escape mutants quickly emerged from infected cells within 24-48 h. Importantly, such adverse viral adaptation was fully prevented with the triple-shRNA AAV vector even during long-term cultivation. In addition, AAV-SAVIOR efficiently purged SARS-CoV-2 in a new model of chronically infected human intestinal cells. Finally, intranasal AAV-SAVIOR delivery using an AAV9 capsid moderately diminished viral loads and/or alleviated disease symptoms in hACE2-transgenic or wild-type mice infected with human or mouse SARS-CoV-2 strains, respectively. Our combinatorial and customizable AAV/RNAi vector complements ongoing global efforts to control the coronavirus disease 2019 (COVID-19) pandemic and holds great potential for clinical translation as an original and flexible preventive or therapeutic antiviral measure.
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COVID-19 , SARS-CoV-2 , Animales , Antivirales , COVID-19/prevención & control , Dependovirus , Ratones , Pandemias , Interferencia de ARN , ARN Interferente Pequeño/genética , SARS-CoV-2/genéticaRESUMEN
INTRODUCTION: There is a significant unmet need for cleft repair in low-income countries. The procedure is challenging due to limited access, small fragile flaps, and the depth at which sutures need to be placed. The aim of this analysis is to review available literature pertaining to cleft lip and palate repair training, with a focus on those applicable to low-income countries. METHODOLOGY: Literature searches of Medline and EMBase were performed to identify studies of cleft lip and/or palate training. Terms including "cleft," "lip," "palate," and "training" were searched. Literature published in English from inception to May 2021 in which the full text was available was considered for inclusion. Studies were included on the basis that they included interventions such as virtual/online training, simulation training, courses, fellowships, and/or hospital-based training. Studies that met this criterion were further assessed using a validated scoring tool then the applicability of each training strategy for low-income countries reviewed. RESULTS: Nineteen studies were included in this analysis. Of these 4 studies pertained to online training, 11 studies illustrated cleft models and simulation training, while 4 studies highlighted the role of charity led training achieved through direct hospital teaching and fellowship programs. The training strategies described have been summarised and presented herein in a narrative format. The simplicity, fidelity, and training benefit of palatoplasty models has also been described. CONCLUSIONS: Cleft lip and palate repair training should be accessible to surgeons in low-income countries. Direct practical experience has an important role in training to perform cleft procedures. Affordable, simple simulation models that resemble human tissue are essential so that surgeons can safely practice skills between initial training and operating on a living child.
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Labio Leporino , Fisura del Paladar , Procedimientos de Cirugía Plástica , Labio Leporino/cirugía , Fisura del Paladar/cirugía , Humanos , Lactante , Recién Nacido , Procedimientos de Cirugía Plástica/métodos , Colgajos Quirúrgicos/cirugíaRESUMEN
BACKGROUND: Cosmeceutical products are an important therapeutic option for facial rejuvenation. Of these, topical application of growth factors has been shown to increase dermal collagen synthesis, improve skin texture, and reduce fine lines and wrinkles. Limited data exist for the use of growth factors in combination with microneedling. OBJECTIVE: This prospective, single-center, uncontrolled study evaluated the efficacy of topical growth factor treatment in conjunction with transdermal delivery of growth factors via home-based microneedling for facial skin rejuvenation. PATIENTS/METHODS: Eleven healthy female individuals aged 33-61 years, with mild-moderate facial wrinkling were included in the study. Over 3 months, participants received twice-daily application of a topical recombinant human growth factor preparation (SkinGenuity® Regenerative and Reparative Serums) along with twice-weekly transdermal delivery of growth factors using a home-based microneedling (0.2 mm) device. Objective skin analysis (VISIA® ) and a subjective patient-reported outcome (FACE-Q® ) assessment measuring satisfaction with appearance were performed at baseline and after 3 months. RESULTS: Objective skin analysis showed a significant improvement in skin texture (17.6%, p < 0.001), wrinkles (17.3%, p < 0.001), red areas (12.4%, p =0.004), and brown spots (6.0%, p =0.03) at 3 months follow-up. FACE-Q scales showed a significant improvement from baseline, including satisfaction with skin, facial appearance, nasolabial folds, cheeks, and lower face/jawline (all p ≤ 0.02). Numerical improvement in adverse effects related to skin was also observed (p = 0.07). No serious adverse effects were reported. CONCLUSIONS: Three months of twice-daily topical growth factor treatment in conjunction with transdermal delivery of growth factors via microneedling improved skin analysis parameters and participant-reported outcome measures, indicative of facial skin rejuvenation.