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Our objectives were to describe time intervals of EMS encounters for suspected stroke patients in North Carolina (NC) and evaluate differences in EMS time intervals by community socioeconomic status (SES) and rurality.This cross-sectional study used statewide data on EMS encounters of suspected stroke in NC in 2019. Eligible patients were adults requiring EMS transport to a hospital following a 9-1-1 call for stroke-like symptoms. Incident street addresses were geocoded to census tracts and linked to American Community Survey SES data and to rural-urban commuting area (RUCA) codes. Community SES was defined as high, medium, or low based on tertiles of an SES index. Urban, suburban, and rural tracts were defined by RUCA codes 1, 2-6, and 7-10, respectively. Multivariable quantile regression was used to estimate how the median and 90th percentile of EMS time intervals varied by community SES and rurality, adjusting for each other; patient age, gender, and race/ethnicity; and incident characteristics.We identified 17,117 eligible EMS encounters of suspected stroke from 2028 census tracts. The population was 65% 65+ years old; 55% female; and 69% Non-Hispanic White. Median response, scene, and transport times were 8 (interquartile range, IQR 6-11) min, 16 (IQR 12-20) min, and 14 (IQR 9-22) minutes, respectively. In quantile regression adjusted for patient demographics, minimal differences were observed for median response and scene times by community SES and rurality. The largest median differences were observed for transport times in rural (6.7 min, 95% CI 5.8, 7.6) and suburban (4.7 min, 95% CI 4.2, 5.1) tracts compared to urban tracts. Adjusted rural-urban differences in 90th percentile transport times were substantially greater (16.0 min, 95% CI 14.5, 17.5). Low SES was modesty associated with shorter median (-3.3 min, 95% CI -3.8, -2.9) and 90th percentile (-3.0 min, 95% CI -4.0, -2.0) transport times compared to high SES tracts.While community-level factors were not strongly associated with EMS response and scene times for stroke, transport times were significantly longer rural tracts and modestly shorter in low SES tracts, accounting for patient demographics. Further research is needed on the role of community socioeconomic deprivation and rurality in contributing to delays in prehospital stroke care.

Introduction Linking emergency medical services (EMS) data to emergency department (ED) data enables assessing the continuum of care and evaluating patient outcomes. We developed novel methods to enhance linkage performance and analysis of EMS and ED data for opioid overdose surveillance in North Carolina. Methods We identified data on all EMS encounters in North Carolina during January 1–November 30, 2017, with documented naloxone administration and transportation to the ED. We linked these data with ED visit data in the North Carolina Disease Event Tracking and Epidemiologic Collection Tool. We manually reviewed a subset of data from 12 counties to create a gold standard that informed developing iterative linkage methods using demographic, time, and destination variables. We calculated the proportion of suspected opioid overdose EMS cases that received International Classification of Diseases, Tenth Revision, Clinical Modification diagnosis codes for opioid overdose in the ED. Results We identified 12 088 EMS encounters of patients treated with naloxone and transported to the ED. The 12-county subset included 1781 linkage-eligible EMS encounters, with historical linkage of 65.4% (1165 of 1781) and 1.6% false linkages. Through iterative linkage methods, performance improved to 91.0% (1620 of 1781) with 0.1% false linkages. Among statewide EMS encounters with naloxone administration, the linkage improved from 47.1% to 91.1%. We found diagnosis codes for opioid overdose in the ED among 27.2% of statewide linked records. Practice Implications Through an iterative linkage approach, EMS–ED data linkage performance improved greatly while reducing the number of false linkages. Improved EMS–ED data linkage quality can enhance surveillance activities, inform emergency response practices, and improve quality of care through evaluating initial patient presentations, field interventions, and ultimate diagnoses.

BACKGROUND Delays in the diagnosis of genetic syndromes are common, particularly in low and middle-income countries with limited access to genetic screening services. We, therefore, aimed to develop and evaluate a machine learning-based screening technology using facial photographs to evaluate a child's risk of presenting with a genetic syndrome for use at the point of care. METHODS In this retrospective study, we developed a facial deep phenotyping technology based on deep neural networks and facial statistical shape models to screen children for genetic syndromes. We trained the machine learning models on facial photographs from children (aged

Although a trustworthy connection between doctor and patient is crucial in clinical practice, it could be hindered by different cultural and linguistic backgrounds. Moreover, an effective doctor-patient interaction could be even more challenging in andrological fields, in which psychological and social components are predominant.To analyse the doctor-patient relationship in the andrological field, applying both qualitative and quantitative analyses.monocentric, cross-sectional, observational study was performed between May and December 2018. During the study, all patients aged18 years attending the Modena Andrology Unit for couple infertility or erectile dysfunction were enrolled and the doctor-patients interaction recorded. Patients were divided into two groups depending on their medical seeking and were further divided between native and non-native speakers of Italian. All patients underwent a routine andrological examination. Every first medical consultation was audio-recorded and transcribed using "ELAN" software for socio-linguistic analysis. Transcriptions underwent qualitative analysis through conversation analysis. Then, quantitative analyses were performed, and interaction parameters underwent correlation analyses.Twenty-five patients were enrolled. The analysis of the andrological interview allowed to recognise five consecutive phases, following a semi-standardized pattern. Patients without linguistic barriers and with infertility problems showed more autonomous contribution during the consultation. No difference arose in the sexual dysfunctions group. Doctor's explanations were frequent, but when linguistic barrier was present or Italian patients seemed less talkative, explanations were shorter, and doctors tried to use other conversational mechanisms to promote understanding. Patient's variables were significantly lower compared to the doctor, considering the number of turns (p = 0.025) and their minimum (p = 0.032), maximum (p0.001), and average durations (p0.001). Only patient's latency was significantly higher than the doctor's (p = 0.001).This is the first attempt to analyse the doctor-patient relationship in andrology using authentic audio-recorded consultations. The results confirmed that a patient-centred communication must be applied also in andrological consultations. However, the topics discussed may require more "medical formulation" to be acceptable to the participants in this context.

Study objective To describe out-of-hospital ketamine use, patient outcomes, and the potential contribution of ketamine to patient death. Methods We retrospectively evaluated consecutive occurrences of out-of-hospital ketamine administration from January 1, 2019 to December 31, 2019 reported to the national ESO Data Collaborative (Austin, TX), a consortium of 1,322 emergency medical service agencies distributed throughout the United States. We descriptively assessed indications for ketamine administration, dosing, route, transport disposition, hypoxia, hypercapnia, and mortality. We reviewed cases involving patient death to determine whether ketamine could be excluded as a potential contributing factor. Results Indications for out-of-hospital ketamine administrations in our 11,291 patients were trauma/pain (49%; n=5,575), altered mental status/behavioral indications (34%; n=3,795), cardiovascular/pulmonary indications (13%; n=1,454), seizure (2%; n=248), and other (2%; n=219). The highest median dose was for altered mental status/behavioral indications at 3.7 mg/kg (interquartile range, 2.2 to 4.4 mg/kg). Over 99% of patients (n=11,274) were transported to a hospital. Following ketamine administration, hypoxia and hypercapnia were documented in 8.4% (n=897) and 17.2% (n=1,311) of patients, respectively. Eight on-scene and 120 in-hospital deaths were reviewed. Ketamine could not be excluded as a contributing factor in 2 on-scene deaths, representing 0.02% (95% confidence interval 0.00% to 0.07%) of those who received out-of-hospital ketamine. Among those with in-hospital data, ketamine could not be excluded as a contributing factor in 6 deaths (0.3%; 95% confidence interval 0.1% to 0.7%). Conclusion In this large sample, out-of-hospital ketamine was administered for a variety of indications. Patient mortality was rare. Ketamine could not be ruled out as a contributing factor in 8 deaths, representing 0.07% of those who received ketamine.

Contemporary data on outcomes in open thoracoabdominal aortic aneurysm (TAAA) repair are limited to reports from major aortic referral centers showing excellent outcomes. This study aimed to characterize the national experience of open TAAA repair using national outcomes data, with a primary focus on the association of hospital volume with mortality and morbidity.The Nationwide Inpatient Sample was queried from 1998 to 2011, and all patients with a diagnosis of TAAA who underwent open operative repair were included. These patients were further stratified into tertiles based on the operative volume of the institution that performed the operation: low volume (LV), 3 cases/y; medium volume (MV), 3 to 11 cases/y; and high volume (HV), ≥12 cases/y. Baseline demographics as well as perioperative outcomes were compared between these groups. Multivariable logistic regression was performed to determine predictors of operative mortality and morbidity. Subgroup analyses were performed for patients presenting for elective surgery and for those presenting for urgent and emergent surgery.Overall operative mortality was 21% for the entire cohort. Operative mortality was higher at LV (26%) and MV (21%) centers compared with HV centers (15%; P .001). This difference was similar in both elective surgery (LV, 18%; MV, 14%; HV, 12%; P .001) and urgent and emergent surgery (LV, 34%; MV, 30%; HV, 19%; P .001). Furthermore, rates of blood transfusion and acute renal failure were significantly lower in the HV group. Multivariable analysis revealed that compared with the HV group, patients operated on at LV centers (odds ratio [OR], 1.9, 95% confidence interval [CI], 1.7-2.1; P .001) and MV centers (OR, 1.5; 95% CI, 1.4-1.7; P .001) had at least 1.5 times the odds of in-hospital mortality. The HV group also had significantly lower odds of dying in the subgroup analyses of both elective surgery and urgent and emergent surgery. Increasing TAAA volume was associated with increased use of distal aortic perfusion (OR, 1.03; 95% CI, 1.02-1.03; P .001).Patients with TAAA in the United States operated on at HV centers have significantly lower mortality and morbidity compared with patients operated on at lower volume centers. Consideration of referral to HV centers may be warranted, but further research is required to justify this conclusion.

Few studies have examined the prehospital presentation, assessment, or treatment of patients diagnosed with coronavirus disease 2019 (COVID-19). The objective of this preliminary report is to describe prehospital encounters for patients with a COVID-19 hospital diagnosis and/or COVID-19 EMS suspicion versus those with neither a hospital diagnosis nor EMS suspicion of the disease.This case series evaluated electronic patient care records from EMS agencies participating in a large national bi-directional data exchange. All records for 9-1-1 responses between March 1 and April 19, 2020, resulting in transport to a hospital, with at least one ICD-10 outcome returned via the data exchange were included. Hospital ICD-10 codes used to determine COVID-19 diagnoses included B97.2, B97.21, B97.29, B34.2, and U07.1. COVID-19 EMS suspicion was defined as a documented EMS primary or secondary impression of COVID-19, or indication of COVID-19 suspicion in the prehospital free-text narrative. Comparisons were stratified by COVID-19 hospital diagnosis and COVID-19 EMS suspicion. Descriptive and comparative statistics are presented.There were 84,540 EMS patient records with linked hospital ICD-10 codes included. Of those, 814 (1%) patients had a COVID-19 hospital diagnosis. Overall, COVID-19 EMS suspicion was documented for 3,204 (4%) patients. A COVID-19 EMS suspicion was documented for 636 (78%) of hospital diagnosed COVID-19 patients. Those with COVID-19 hospital diagnoses were more likely to present with tachycardia, tachypnea, hypoxia, and fever during the EMS encounter. EMS responses for patients diagnosed with COVID-19 were also more likely to originate from a skilled nursing/assisted living facility. EMS PPE (eye protection, mask, or gown) use was more frequently documented on records of patients who had hospital diagnosed COVID-19.In this large sample of prehospital encounters, EMS COVID-19 suspicion demonstrated sensitivity of 78% and positive predictive value of 20% compared with hospital ICD-10 codes. These data indicate that EMS suspicion alone is insufficient to determine appropriate utilization of PPE.

Background We aimed to determine the prevalence of decreased kidney function in a potential chronic kidney disease (KD) of unknown aetiology hotspot in Mexico, assess its distribution across occupations and examine the associated risk factors. Methods A cross-sectional study collected sociodemographic, occupational, medical and biometric data from 616 men and women aged 20–60 years who were residents of three communities within the Tierra Blanca region in Mexico. Kidney function was assessed by standardized serum creatinine and estimated glomerular filtration rate (eGFR) and semi-quantitative albumin-to-creatinine ratio (ACR). To examine the distribution of decreased kidney function within the population, age- and sex-adjusted prevalence of low eGFR (≤60 mL/min/1.73 m2) was estimated for all participants and across occupations. Multivariable logistic regression was used to assess the association of occupation with having low eGFR. Results Of the 579 participants analysed (37 excluded due to missing data), the age- and sex-adjusted prevalence of low eGFR was 3.5%. Agriculture was the occupation associated with the highest adjusted prevalence of low eGFR (8.8%), with 1 in every 11 agricultural workers having low eGFR. Working in agriculture was independently associated with more than a 5-fold risk of having low eGFR [odds ratio 5.2 (95% confidence interval 1.1–24.3), P = 0.032], after adjustment for age, sex, diabetes, hypertension, body mass index, ACR and family history of KD. Additionally, a quarter of the population (25%) had either low eGFR or an ACR >30 mg/g, mostly due to albuminuria. Conclusions Our work suggests that there is a high prevalence of decreased kidney function in Tierra Blanca, particularly amongst agricultural workers.

In 2011, a multidisciplinary hypertrophic cardiomyopathy (HCM) program with a dedicated myectomy surgeon was implemented at our institution. We hypothesized that a dedicated approach allows better identification and management of mitral regurgitation (MR) during septal myectomy (SM) for obstructive HCM with significant mitral regurgitation. Between 2006 and 2018, 181 patients had SM at our institution. This study consists of 53 patients with preoperative moderate or greater MR associated with systolic anterior motion who underwent isolated SM with or without mitral intervention. Patients were divided into those who underwent SM by a dedicated myectomy surgeon (group D, n = 31) or by a non-dedicated surgeon (group ND, n = 22). Primary outcome of interest was rate of mitral valve replacement (MVR) at SM. Secondary outcomes include in-hospital mortality, need for permanent pacemaker, mitral valve reoperation, and residual MR and left ventricular outflow tract gradient on postoperative echocardiography. 12 patients (55%) had a concomitant MVR during septal myectomy in group ND compared to 2 patients (6%) in group D (p

Objective: Mitral regurgitation (MR) induced by systolic anterior motion in patients with hypertrophic cardiomyopathy (HCM) can frequently be abolished with a proficient septal myectomy (SM) without the need for mitral-valve replacement (MVR). ACC guidelines stress the importance of volume in improving outcomes after SM, but there is a lack of data measuring the impact of volume on the need for MVR during SM. This study was designed to assess the impact of institutional volume on MVR rates using national outcomes data. Methods: The Nationwide Inpatient Sample was queried from 1998 to 2011 and a total of 6,207 patients had a diagnosis of HCM and a procedure code for SM. Outcomes were compared between patients who underwent SM (group I) and SM and MVR (group II). Furthermore, patients were stratified into 3 groups based on the number of SMs at the performing institution: low experience (1–24 cumulative SMs), medium experience (25–49 SMs), and high experience (>50 SMs). These patients underwent multivariable analysis to determine the impact of institutional volume on MVR rate. Results: The total MVR rate was 26%. Perioperative outcomes were worse, i.e., there were higher rates of mortality, kidney injury, and urinary complications, in group II than in group I. Only 37.6% of patients were operated on at institutions meeting the guideline criteria of >50 cumulative SMs. When compared to patients in the high-experience group, patients in the low- (OR 2.7, 95% CI 2.3–3.2, p < 0.05) and medium-experience (OR 3.0, 95% CI 2.5–3.6, p < 0.05) groups were more likely to undergo MVR. Conclusion: Compared to reports from SM reference centers, national data suggest that MVR rates are quite high at SM. Patients undergoing SM at centers that do not meet the guideline standard have >2.5× the odds of undergoing MVR compared to those operated on at guideline-endorsed centers.

We aimed with the present study to fill the gap on the performance and safety of stroke management and the costs related to hospitalizations, the relevant comorbidities associated with stroke patients, and the stroke patient outcomes health-related quality of life (HRQOL) progress. Our study investigated the clinical, neurological, and social impact of stroke in 220 patients in a tertiary hospital located in the countryside of the state of Santa Catarina, Brazil. Description of clinical and neurological characteristics of stroke patients between 2015 to 2020 was analyzed using electronic medical records. The most affected age group was 61-80 years, being female the most affected sex. Almost 89.5% of the patients had some risk factor, with a higher prevalence of ischemic stroke. This type of stroke was the expensive, in terms of hospitalization, with an average cost of $74.10. Considering the stroke-specific quality of life scale (SSQOL) score, 88.3% of patients who demonstrated some comorbidity and 47.6% of women had lower quality of life levels post-stroke. Our data could be useful to substantiate a data-base with epidemiology statistics characterization of stroke hospitalizations, indicating the severity of stroke for the patient.

Neuropathic pain is a form of chronic pain arising from damage of the neural cells that sense, transmit or process sensory information. Given its growing prevalence and common refractoriness to conventional analgesics, the development of new drugs with pain relief effects constitutes a prominent clinical need. In this respect, drugs that reduce activity of sensory neurons by modulating ion channels hold the promise to become effective analgesics. Here, we evaluated the mechanical antinociceptive effect of IQM-PC332, a novel ligand of the multifunctional protein downstream regulatory element antagonist modulator (DREAM) in rats subjected to chronic constriction injury of the sciatic nerve as a model of neuropathic pain. IQM-PC332 administered by intraplantar ( 0.01–10 μg) or intraperitoneal (0.02–1 μg/kg) injection reduced mechanical sensitivity by ≈100% of the maximum possible effect, with ED50 of 0.27 ± 0.05 μg and 0.09 ± 0.01 μg/kg, respectively. Perforated-patch whole-cell recordings in isolated dorsal root ganglion (DRG) neurons showed that IQM-PC332 (1 and 10 μM) reduced ionic currents through voltage-gated K+ channels responsible for A-type potassium currents, low, T-type, and high voltage-activated Ca2+ channels, and transient receptor potential vanilloid-1 (TRPV1) channels. Furthermore, IQM-PC332 (1 μM) reduced electrically evoked action potentials in DRG neurons from neuropathic animals. It is suggested that by modulating multiple DREAM–ion channel signaling complexes, IQM-PC332 may serve a lead compound of novel multimodal analgesics., This research was funded by Universidad Complutense de Madrid grants: PR75/18- 21593 and FEI20/35 (to A.R.A.), and Ministerio de Ciencia e Innovación, AEI-FEDER, EU grants: SAF2016-75021-R and PID2019-104366RB-C21 (to C.V.), PID2019-109155RB-I00 (to A.R.A.), PID2019- 104366RB-C22 (to M.G.-R), Instituto de Salud Carlos III CIBERCV program: CB/11/00222 (to C.V.); Consejo Superior de Investigaciones Científicas grants: PIE202180E073 (to M.G.-R.), PIE201820E104 and 2019AEP148 (to C.V.). P.G.S. was funded with a fellowship from the Ministerio de Ciencia e Innovación (FPU17/02731).

Non-synaptic transmission is pervasive throughout the nervous system. It appears especially prevalent in peripheral ganglia, where non-synaptic interactions between neighboring cell bodies have been described in both physiological and pathological conditions, a phenomenon referred to as cross-depolarization (CD) and thought to play a role in sensory processing and chronic pain. CD has been proposed to be mediated by a chemical agent, but its identity has remained elusive. Here, we report that in the rat dorsal root ganglion (DRG), the P2Y1 purinergic receptor (P2RY1) plays an important role in regulating CD. The effect of P2RY1 is cell-type specific: pharmacological blockade of P2RY1 inhibited CD in A-type neurons while enhancing it in unmyelinated C-type cells. In the nodose ganglion of the vagus, CD requires extracellular calcium in a large percentage of cells. In contrast, we show that in the DRG extracellular calcium appears to play no major role, pointing to a mechanistic difference between the two peripheral ganglia. Furthermore, we show that DRG glial cells also play a cell-type specific role in CD regulation. Fluorocitrate-induced glial inactivation had no effect on A-cells but enhanced CD in C-cells. These findings shed light on the mechanism of CD in the DRG and pave the way for further analysis of non-synaptic neuronal communication in sensory ganglia.HighlightsThe purinergic receptor P2RY1 plays a regulatory role in non-synaptic crossdepolarization (CD) in the mammalian DRGThe effect of P2RY1 is cell type-specific: it enhances CD in myelinated A-type neurons, but inhibits it in unmyelinated C-cellsCD in the DRG does not require extracellular calcium. This is in contrast with the nodose ganglion, where extracellular calcium plays an important role in nonsynaptic interactionsCD is also modulated by DRG glial cells. Glia selectively inhibit CD in C-type neurons

Summary Low-density cell culture of the postnatal cerebellum, combined with live imaging and single-cell tracking, allows the behavior of postnatal cerebellar neural stem cells (NSCs) and their progeny to be monitored. Cultured cerebellar NSCs maintain their neurogenic nature giving rise, in the same relative proportions that exist in vivo, to the neuronal progeny generated by the three postnatal cerebellar neurogenic niches. This protocol describes the identification of the nature of the progeny through both post-imaging immunocytochemistry and patch-clamp recordings. For complete details on the use and execution of this protocol, please refer to Paniagua-Herranz et al. (2020b)., Graphical abstract, Highlights • Protocol to culture postnatal mouse cerebellar neural stem cells (NSCs) in low density • The behavior of isolated postnatal cerebellar NSC can be monitored at single-cell level • Protocol for simultaneous monitoring of the three postnatal cerebellar neurogenic niches • Procedures of live imaging and single cell tracking for lineage tracing, Low-density cell culture of the postnatal cerebellum, combined with live imaging and single-cell tracking, allows the behavior of postnatal cerebellar neural stem cells (NSCs) and their progeny to be monitored. Cultured cerebellar NSCs maintain their neurogenic nature giving rise, in the same relative proportions that exist in vivo, to the neuronal progeny generated by the three postnatal cerebellar neurogenic niches. This protocol describes the identification of the nature of the progeny through both post-imaging immunocytochemistry and patch-clamp recordings.

BACKGROUND Craniosynostosis typically develops prenatally and creates characteristic changes in craniofacial form. Nevertheless, postnatal forms of craniosynostosis have been described. The purpose of this study was to determine the prevalence of incidentally identified, but temporally premature, cranial suture fusion in normocephalic children. METHODS Computed tomographic scans obtained from children aged 1 to 5 years evaluated in the authors' emergency department between 2005 and 2016 were reviewed for evidence of craniosynostosis. Patients with prior ventriculoperitoneal shunt, brain or cranial abnormality, or known syndromes were excluded. The presence of craniosynostosis and cranial index was assessed by a panel of three craniofacial surgeons and one pediatric neurosurgeon. Demographic information, fusion type, reason for the computed tomographic scan, and medical history were recorded as covariates. Cranial shape and intracranial volume were calculated using a previously validated automated system. RESULTS Three hundred thirty-one patients met the inclusion criteria. The mean age was 2.4 ± 1.3 years. Eleven patients (3.3 percent) were found to have a complete (n = 9) or partial (n = 2) fusion of the sagittal suture. All patients had a normal cranial index (0.80; range, 0.72 to 0.87) and a grossly normal head shape. Only two fusions (18.2 percent) were documented by the radiologist. Cranial shape analysis performed in five of the 11 patients showed subtle phenotypic changes along the scaphocephaly spectrum in four patients, with a normal shape in the remaining case. CONCLUSIONS Sagittal fusion is present in 3.3 percent of otherwise phenotypically normal children aged 1 to 5 years. The clinical significance of this result is unclear, but routine screening of affected patients is paramount. CLINICAL QUESTION/LEVEL OF EVIDENCE Risk, IV.

© 2020 American Society of Andrology and European Academy of Andrology Background: It has recently been suggested that the hypergonadotropic hypogonadism characterizing Klinefelter syndrome (KS) might not be due to a steroidogenic dysfunction per se, but mainly to an altered testosterone (T) secretion into the bloodstream. However, the Leydig cell functionality remains incompletely studied in KS, and new markers should be considered. Previous data indicated that chronic hCG stimulation influences the production of both insulin-like peptide 3 (INSL3) and 25-hydroxy-vitamin D (25-VD) in eugonadal men. Aim of the study: To evaluate INSL3 and 25-VD serum levels, as markers of Leydig cell functionality, in association with sex steroids, after an acute hCG test in a group of KS patients and healthy volunteers. Methods: A retrospective analysis of a prospective case-control clinical trial was carried out. KS patients (n=11) and age-matched healthy controls (n=11) provided a basal blood sample (V0) immediately followed by a single intramuscular injection of hCG 5000IU. Blood samples were taken in the following five days (V1-V5). Results: At baseline, INSL3 was lower in KS patients compared with controls (P=.007). When adjusted for INSL3 levels, the production of steroids was similar between KS patients and controls. 25-VD was in the insufficient range both in KS patients and in controls and was not different (P=.064). Acute hCG stimulation increased neither INSL3 nor 25-VD in both KS patients and controls. In controls, an inverse correlation was detected between INSL3 levels and body mass index (P=.020) and waist circumference (P=.020). Conclusions: INSL3 secretion is independent from steroidogenesis, and its production is mostly not influenced by acute hCG stimulation both in KS men and in controls. INSL3 serum levels should be considered as a marker of Leydig cell differentiation and numbers rather than steroidogenesis. 25-VD serum levels are also not increased by a single acute hCG administration, which was not able to restore the normal concentrations of 25-VD.

Background Timely emergency medical services (EMS) response, management, and transport of patients with suspected acute coronary syndrome (ACS) significantly reduce delays to emergency treatment and improve outcomes. We evaluated EMS response, scene, and transport times and adherence to proposed time benchmarks for patients with suspected ACS in North Carolina from 2011 to 2017. Methods and Results We conducted a population‐based, retrospective study with the North Carolina Prehospital Medical Information System, a statewide electronic database of all EMS patient care reports. We analyzed 2011 to 2017 data on patient demographics, incident characteristics, EMS care, and county population density for EMS‐suspected patients with ACS, defined as a complaint of chest pain or suspected cardiac event and documentation of myocardial ischemia on prehospital ECG or prehospital activation of the cardiac care team. Descriptive statistics for each EMS time interval were computed. Multivariable logistic regression was used to quantify relationships between meeting response and scene time benchmarks (11 and 15 minutes, respectively) and prespecified covariates. Among 4667 patients meeting eligibility criteria, median response time (8 minutes) was shorter than median scene (16 minutes) and transport (17 minutes) time. While scene times were comparable by population density, patients in rural (versus urban) counties experienced longer response and transport times. Overall, 62% of EMS encounters met the 11‐minute response time benchmark and 49% met the 15‐minute scene time benchmark. In adjusted regression analyses, EMS encounters of older and female patients and obtaining a 12‐lead ECG and venous access were independently associated with lower adherence to the scene time benchmark. Conclusions Our statewide study identified urban–rural differences in response and transport times for suspected ACS as well as patient demographic and EMS care characteristics related to lower adherence to scene time benchmark. Strategies to reduce EMS scene times among patients with ACS need to be developed and evaluated.

Undifferentiated embryonal sarcoma of the liver (UESL) is a rare aggressive neoplasm that occurs predominantly in children. Like mesenchymal hamartoma of the liver (MHL), UESL harbors recurrent rearrangements involving 19q13.3 and 19q13.4, a region of the genome that contains a primate-specific cluster of micro-RNAs. Here, we present a case of a high-grade neoplasm that arose in the left hepatic lobe of a 5-year-old male and gave rise to widespread lymph node, visceral, and soft tissue metastases. The tumor was composed of sheets, tubules, and papillae of epithelioid cells with rhabdoid morphology. INI1 and BRG1 expression were retained. Tumor cells diffusely expressed epithelial markers, including multiple keratins. While the morphologic and immunophenotypic features were suggestive of poorly differentiated carcinoma with rhabdoid features, the tumor was found to harbor the t(11;19)(q13;q13.3) translocation characteristic of UESL, as well as a TP53 mutation. Given the clinical presentation, imaging, clinical course, the tumor was classified as UESL with unusual, carcinoma-like histopathologic features. In the context of an unclassified high-grade hepatic tumor in a young child, molecular or cytogenetic testing for chromosome 19q13 alterations should be considered.

Background: Chest pain is a leading complaint in emergency settings. Timely emergency medical services (EMS) responses can reduce delays to treatment and improve clinical outcomes for acute myocard...

Purpose: Kaposiform lymphangiomatosis (KLA) is a rare, frequently aggressive, systemic disorder of the lymphatic vasculature, occurring primarily in children. Even with multimodal treatments, KLA has a poor prognosis and high mortality rate secondary to coagulopathy, effusions and systemic involvement. We hypothesized that, as has recently been found for other vascular anomalies, KLA may be caused by somatic mosaic variants affecting vascular development. Methods: We performed exome sequencing of tumor samples from five individuals with KLA, along with samples from uninvolved control tissue in three of the five. We used digital PCR (dPCR) to validate the exome findings and to screen KLA samples from six other individuals. Results: We identified a somatic activating NRAS variant (c.182A>G, p.Q61R) in lesional tissue from 10/11 individuals, at levels ranging from 1–28%, that was absent from the tested control tissues. Conclusion: The activating NRAS p.Q61R variant is a known ‘hotspot’ variant, frequently identified in several types of human cancer, especially melanoma. KLA, therefore, joins a growing group of vascular malformations and tumors caused by somatic activating variants in the RAS/PI3K/mTOR signalling pathways. This discovery will expand treatment options for these high risk patients as there is potential for use of targeted RAS pathway inhibitors.

Introduction Mucoepidermoid carcinoma is a rare malignant salivary gland neoplasm in the pediatric population. Few studies have discussed best practice with respect to diagnosis and treatment in children. Objective To present our institution's experience with the evaluation and management of pediatric mucoepidermoid carcinoma of the head and neck. Methods Retrospective chart review of patients under 20 years of age diagnosed with mucoepidermoid carcinoma of the head and neck between 1998 and 2017. Data assessed includes demographics, clinical presentation, imaging examinations, histopathology, treatment, complications, local recurrence, distant metastasis, and follow-up. Results Sixteen patients (10 female, 6 male) were identified with a median age of 12.9 (IQR: 10.9–15.0) years. Tumors were located within the parotid gland (n = 11, 68.8%), accessory lobe of the parotid gland (n = 2, 12.5%), palate (n = 2, 12.5%), and submandibular region (n = 1, 6.3%). In 9 patients (56.3%) a neoplastic etiology was suspected based on the clinical and/or radiographic findings and confirmed pathologically on biopsy or excision. All patients were treated surgically and five patients required adjuvant radiotherapy. One patient had recurrence requiring re-excision. Seven patients (43.8%) had transient facial paresis post-operatively and one had Frey syndrome. Median follow-up time was 59.7 months (IQR: 18.9–99.3). Conclusion The malignant nature of mucoepidermoid carcinoma requires comprehensive, multidisciplinary management. Imaging and tissue sampling by fine needle aspiration give clinicians the best insight into location and nature of the mass. Complete surgical excision with attention to preservation of facial nerve and achieving negative margins is desired.

OBJECTIVE: Prehospital electrocardiography (ECG) is recommended for patients with suspected acute coronary syndrome (ACS), yet only 20–80% of chest pain patients receive a prehospital ECG. Less is known about prehospital ECG use in patients with less common complaints (e.g., fatigue) suspicious for ACS who are transported by emergency medical services (EMS). The aims of this study were to determine: 1) the proportion of patients with chest pain and less typical complaints, and 2) patient characteristics associated with prehospital ECG use in patients transported by EMS to emergency departments across North Carolina. METHODS: A novel linked database was created between prehospital and emergency department (ED) patient care data from the North Carolina Prehospital Medical Information System and the North Carolina Disease Event Tracking and Epidemiologic Collection Tool. Institutional review board approval and a data use agreement were received prior to the start of the study. Patients ≥ 21 transported during 2010–2014 by EMS with select variables were included. We examined patients’ complaints (symptoms), characteristics (e.g., race, ethnicity, final hospital diagnosis), and prehospital ECG use (yes/no). Analysis included descriptive statistics and mixed logistic regression. RESULTS: During 2010–2014, there were 1,967,542 patients with linked EMS-ED data (mean age: 56.9 [SD: 22.2], 43.2% male, 63.7% White). Of these, 643,174 (32.6%) received a prehospital ECG. Patients with prehospital ECG presented with the following complaints: 20% chest pain; 10% shortness of breath; 6% abdominal pain/problems; 6% altered level of consciousness; 5% syncope/dizziness; 4% palpitations; 12% other complaints; and 37% missing. Patients’ presenting complaints were the strongest predictor of prehospital ECG use, adjusting for age, sex, race, ethnicity, urbanicity, and date and time of EMS dispatch. CONCLUSIONS: Patients with chest pain were significantly more likely to receive a prehospital ECG compared to those with less typical but suspicious complaints for ACS. Patients with less common presentations remain disadvantaged for early triage, risk stratification, and intervention prior to the hospital.

Lipofibromatosis is a rare pediatric soft tissue tumor with predilection for the hands and feet. Previously considered to represent "infantile fibromatosis", lipofibromatosis has distinctive morphological features, with mature adipose tissue, short fascicles of bland fibroblastic cells, and lipoblast-like cells. Very little is known about the genetic underpinnings of lipofibromatosis. Prompted by our finding of the FN1-EGF gene fusion, previously shown to be a characteristic feature of calcifying aponeurotic fibroma (CAF), in a morphologically typical case of lipofibromatosis that recurred showing features of CAF, we studied a cohort of 20 cases of lipofibromatosis for this and other genetic events. The cohort was composed of 14 males and 6 females (median age 3 years; range 1 month-14 years). All primary tumors showed classical lipofibromatosis morphology. Follow-up disclosed three local recurrences, two of which contained calcifying aponeurotic fibroma-like nodular calcifications in addition to areas of classic lipofibromatosis, and no metastases. By FISH and RNA sequencing, four cases were positive for FN1-EGF and one case each showed an EGR1-GRIA1, TPR-ROS1, SPARC-PDGFRB, FN1-TGFA, EGFR-BRAF, VCL-RET, or HBEGF-RBM27 fusion. FN1-EGF was the only recurrent fusion, suggesting that some cases of "lipofibromatosis" may represent calcifying aponeurotic fibroma lacking hallmark calcifications. Several of the genes involved in fusions (BRAF, EGFR, PDGFRB, RET, and ROS1) encode receptor tyrosine kinases (RTK), or ligands to the RTK EGFR (EGF, HBEGF, TGFA), suggesting a shared deregulation of the PI3K-AKT-mTOR pathway in a large subset of lipofibromatosis cases.

Cornelia de Lange syndrome (CdLS) is a dominant multisystemic malformation syndrome due to mutations in five genes-NIPBL, SMC1A, HDAC8, SMC3, and RAD21. The characteristic facial dysmorphisms include microcephaly, arched eyebrows, synophrys, short nose with depressed bridge and anteverted nares, long philtrum, thin lips, micrognathia, and hypertrichosis. Most affected individuals have intellectual disability, growth deficiency, and upper limb anomalies. This study looked at individuals from diverse populations with both clinical and molecularly confirmed diagnoses of CdLS by facial analysis technology. Clinical data and images from 246 individuals with CdLS were obtained from 15 countries. This cohort included 49% female patients and ages ranged from infancy to 37 years. Individuals were grouped into ancestry categories of African descent, Asian, Latin American, Middle Eastern, and Caucasian. Across these populations, 14 features showed a statistically significant difference. The most common facial features found in all ancestry groups included synophrys, short nose with anteverted nares, and a long philtrum with thin vermillion of the upper lip. Using facial analysis technology we compared 246 individuals with CdLS to 246 gender/age matched controls and found that sensitivity was equal or greater than 95% for all groups. Specificity was equal or greater than 91%. In conclusion, we present consistent clinical findings from global populations with CdLS while demonstrating how facial analysis technology can be a tool to support accurate diagnoses in the clinical setting. This work, along with prior studies in this arena, will assist in earlier detection, recognition, and treatment of CdLS worldwide.

Background: The use of health services is a complex behavioral phenomenon affected by multiple factors (availability, distance, cost, quality, attitudes, cultural beliefs, socioeconomic characteristics, and individuals’ self-perception of health). Mexico has a segmented health system, and the access to it depends on the labor insertion and the population’s ability to pay. Objective: To assess association between use of health services and cardiovascular and metabolic syndrome risk factors among Mexican adults. Methods: Analytical cross-sectional nationally representative study carried out on Mexican adults (≥20-year-old adults of both sexes, n = 4595). Socioeconomic factors, geographic area, health care coverage, information about the use of health services, previous medical diagnoses of diabetes and hypertension, and smoking were assessed. Anthropometrics, triglyceride, total cholesterol, HDL-cholesterol, and glucose plasma levels were measured. Metabolic syndrome (MetS) and cardiovascular risk factors were assessed. Prevalences were expressed in terms of percentages, and significant differences were calculated using χ2 test. Univariate and multivariate analysis was performed to evaluate the association between the use of health services and cardiovascular risk factors and sociodemographic variables. Results: The probability of using health services is higher and more significant in subjects with obesity, diabetes (OR (95% CI): 1.73 (1.49–2.00, p &lt, 0.001), hypertension (OR (95% CI): 1.29 (1.14–1.45, 0.001), hypertriglyceridemia (OR (95% CI): 1.30 (1.15–1.46, 0.001), and in those with hypercholesterolemia (OR (95% CI): 1.23 (1.03–1.39, p = 0.001). Conclusions: Among health service users, there is a positive significant association between the use of health services and the presence of metabolic syndrome, obesity, diabetes, hypertension, hypertriglyceridemia, and hypercholesterolemia.

Congenital tufting enteropathy (CTE) is a rare heritable cause of intractable diarrhea due to EPCAM mutation. Pathologic findings include intestinal villous atrophy, tufted discohesive tear-drop-shaped epithelium, and a normal brush border. In affected patients, absent intestinal epithelial cell adhesion molecule (EpCAM) expression results in loss of MOC31 immunostaining. CTE liver pathology has not yet been described. We identified CTE patients with liver biopsies and reviewed clinicopathologic material including MOC31 immunohistochemistry. Three CTE patients had 4 liver core biopsies (at ages 1, 5, 7, and 16 y), 2 for preintestinal transplant evaluation, and 2 (from a single patient) for pretreatment assessment of chronic hepatitis C; all had received parenteral nutrition (PN). All samples showed loss of biliary epithelial polarization and mild portal and lobular inflammation. Only the hepatitis C patient demonstrated fibrosis. One patient each had lobular neutrophilic microabscesses and macrovesicular steatosis. Proliferative ductular reactions were absent in CTE patients but present in all controls on PN for other reasons. MOC31 was absent in biliary epithelium and hepatocytes of all CTE patients; controls showed consistent strong membranous biliary epithelial and patchy membranous periportal hepatocyte staining. Our data show that, histologically, hepatopathy in CTE can be difficult to separate from comorbid disease including PN effect; however, the absent ductular reaction may be characteristic. MOC31 localization in the biliary epithelium and zone 1 hepatocytes of controls suggests these compartments of the liver might be most susceptible to effects of EpCAM deficiency. In addition, we validate the liver as suitable tissue for CTE diagnosis using MOC31 immunohistochemistry.

Popular parametric and semiparametric hazards regression models for clustered survival data are inappropriate and inadequate when the unknown effects of different covariates and clustering are complex. This calls for a flexible modeling framework to yield efficient survival prediction. Moreover, for some survival studies involving time to occurrence of some asymptomatic events, survival times are typically interval censored between consecutive clinical inspections. In this article, we propose a robust semiparametric model for clustered interval-censored survival data under a paradigm of Bayesian ensemble learning, called Soft Bayesian Additive Regression Trees or SBART (Linero and Yang, 2018), which combines multiple sparse (soft) decision trees to attain excellent predictive accuracy. We develop a novel semiparametric hazards regression model by modeling the hazard function as a product of a parametric baseline hazard function and a nonparametric component that uses SBART to incorporate clustering, unknown functional forms of the main effects, and interaction effects of various covariates. In addition to being applicable for left-censored, right-censored, and interval-censored survival data, our methodology is implemented using a data augmentation scheme which allows for existing Bayesian backfitting algorithms to be used. We illustrate the practical implementation and advantages of our method via simulation studies and an analysis of a prostate cancer surgery study where dependence on the experience and skill level of the physicians leads to clustering of survival times. We conclude by discussing our method's applicability in studies involving high dimensional data with complex underlying associations.

One of the physiologic mechanisms responsible to maintain asymmetric phospholipid distribution (in particular phosphatidylserine, PS) in human erythrocyte membranes is orchestrated by the balance between enzymes responsible for active transport of PS from the outer to the inner leaflet (ATP11C) and those whose counteracts these activities (PLSCR1). Using quantitative real-time polymerase chain reaction and standard flow cytometry procedures, we hypothesized that the aberrant expression of either or both ATP11C and PLSCR1 transcripts may disrupt the PS internalization/externalization process and become clinically relevant for patients with sickle cell anemia (SCA). Overall, neither ATP11C/PLSCR1 ratio or ATP11C and PLSCR1 (if analyzed separately) had impact on risk to present acute or chronic organ damage in 178 patients with SCA. By collecting a new set of samples from SCA patients during a vaso-occlusive crisis (VOC, crisis state, 13 patients) and comparing with new samples of patients in steady state (15 patients), we noticed that patients in steady state exhibited mean values of ATP11C/PLSCR1 ratio significantly higher (mean value: 18.2, range, 0.3-53) than those who were in crisis (mean value: 3.7, range, 0.5-9) (P = 0.013). Most importantly, there was a strong inverse correlation between PS exposure and ATP11C/PLSCR1 ratio in sickle erythrocytes (Pearson correlation coefficient, r: - 0.78). Based on these findings, it is conceivable that the ATP11C/PLSCR1 ratio may switch from high to low during a VOC, although the underlying reasons require further investigations.

Deregulated cellular energetics is formally incorporated as an emerging hallmark of cancer, however little is known about its processes in myelodysplastic syndromes (MDS). Using transcriptomic data of CD34+ cells from 159 MDS patients and 17 healthy donors, we selected 37 genes involved in cellular energetics and interrogated about its clinical and prognostic functions. Based on the low expression of ACLY, ANPEP, and PANK1, as well as high expression of PKM and SLC25A5, we constructed our Molecular-Based Score (MBS), that efficiently discriminated patients at three risks groups: favourable risk (n = 28; 3-year overall survival (OS): 100%); intermediate (n = 60; 76% [62–93%]) and adverse (n = 71; 35% [17–61%]). Adverse MBS risk was independently associated with inferior OS (HR = 10.1 [95% CI 1.26–81]; P = 0.029) in multivariable analysis using age, gender and the revised international prognostic score system as confounders. Transcriptional signature revealed that Favourable- and intermediate-risk patients presented enriched molecular programs related to mature myeloid progenitors, cell cycle progression, and oxidative phosphorylation, indicating that this cells differs in their origin, metabolic state, and cell cycle regulation, in comparison to the adverse-risk. Our study provides the first evidence that cellular energetics is transcriptionally deregulated in MDS CD34+ cells and establishes a new useful prognostic score based on the expression of five genes.

Made available in DSpace on 2021-06-25T12:37:39Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-01-01. Added 1 bitstream(s) on 2021-07-15T14:36:33Z : No. of bitstreams: 1 S0036-46652021000100600.pdf: 157025 bytes, checksum: 90bccd804f2cf9e9739451a8ffd330ab (MD5) Instituto Butantan Fundacao Butantan This cross-sectional seroepidemiological survey presents the seroprevalence of SARS-CoV-2 in a population living in 15 Long-Term Care Facilities (LTCFs). after two intra-institutional outbreaks of COVID-19 in the city of Botucatu, Sao Paulo State, Brazil. Residents were invited to participate in the serological survey performed in June and July 2020. Sociodemographic and clinical characterization of the participants as well as the LTCF profile were recorded. Blood samples were collected, processed and serum samples were tested using the rapid One Step COVID-19 immunochromatography test to detect IgM and IgG anti-SARS-CoV-2. Among 209 residents, the median of age was 81 years old, 135 (64.6%) were female and 171 (81.8%) self-referred as being white. An overall seroprevalence of 11.5% (95% CI: 7.5% - 16.6%) was found. The highest seroprevalences of 100% and 76.9% were observed in LTCFs that had experienced COVID-19 outbreaks. Most residents with positive immunochromatography tests (70.8%) referred previous contact with a confirmed COVID-19 case. Although there was a relatively low seroprevalence of COVID-19 in the total number of elderly people, this population is highly vulnerable and LTCFs are environments at higher risk for COVID-19 dissemination. A well-established test for COVID-19 policies, the adequate characterization of the level of interaction between residents and the healthcare provider team and the level of complexity of care are crucial to monitor and control the transmission of SARS-CoV-2 in these institutions. Ctr Farmacovigilancia Seguranca Clin & Gestao Ris, Inst Butantan, Av Vital Brasil 1500, BR-05503900 Sao Paulo, SP, Brazil Univ Estadual Paulista, Fac Med Botucatu, Dept Clin Med, Botucatu, SP, Brazil Univ Sao Paulo, Fac Saude Publ, Sao Paulo, SP, Brazil Univ Sao Paulo, Fac Med, Dept Pediat, Sao Paulo, SP, Brazil Univ Estadual Paulista, Fac Med Botucatu, Dept Clin Med, Botucatu, SP, Brazil

Introduction Patients with Noonan and Williams–Beuren syndrome present similar facial phenotypes modulated by their ethnic background. Although distinctive facial features have been reported, studies show a variable incidence of those characteristics in populations with diverse ancestry. Hence, a differential diagnosis based on reported facial features can be challenging. Although accurate diagnoses are possible with genetic testing, they are not available in developing and remote regions. Methods We used a facial analysis technology to identify the most discriminative facial metrics between 286 patients with Noonan and 161 with Williams‐Beuren syndrome with diverse ethnic background. We quantified the most discriminative metrics, and their ranges both globally and in different ethnic groups. We also created population‐based appearance images that are useful not only as clinical references but also for training purposes. Finally, we trained both global and ethnic‐specific machine learning models with previous metrics to distinguish between patients with Noonan and Williams–Beuren syndromes. Results We obtained a classification accuracy of 85.68% in the global population evaluated using cross‐validation, which improved to 90.38% when we adapted the facial metrics to the ethnicity of the patients (p = 0.024). Conclusion Our facial analysis provided for the first time quantitative reference facial metrics for the differential diagnosis Noonan and Williams–Beuren syndromes in diverse populations., Although distinctive facial features have been reported between Noonan and Williams–Beuren syndromes, studies have found a variable incidence of those characteristics in populations with diverse ancestry. We sought to identify and quantify facial features discriminative of these two syndromes in population with diverse ancestry using facial analysis. We provide for the first time quantitative reference facial metrics in diverse populations that can be used both at the clinic and for training purposes.

Personalized medicine has largely failed to produce curative therapies in advanced cancer patients. Evaluation of in situ drug target availability (DTA) concomitant with local protein expression is critical to an accurate assessment of therapeutic efficacy, but tools capable of both are currently lacking. We developed and optimized a fluorescence imaging platform termed TRIPODD (Therapeutic Response Imaging through Proteomic and Optical Drug Distribution), resulting in the only methodology capable of simultaneous quantification of single-cell DTA and protein expression with preserved spatial context within a tumor. Using TRIPODD, we demonstrate the feasibility of combining two complementary fluorescence imaging techniques, intracellular paired agent imaging (iPAI) and cyclic immunofluorescence (cyCIF), conducted with oligonucleotide-conjugated antibodies (Ab-oligos) on tissue samples. We successfully performed sequential imaging on a single tissue section of iPAI to capture single-cell DTA and local protein expression heterogeneity using Ab-oligo cyCIF. Fluorescence imaging data acquisition was followed by spatial registration resulting in high dimensional data correlating DTA to protein expression at the single-cell level where uptake of a targeted probe alone was not well correlated to protein expression. Herein, we demonstrated the utility of TRIPODD as a powerful imaging platform capable of interpreting tumor heterogeneity for a mechanistic understanding of therapeutic response and resistance through quantification of drug target availability and proteomic response with preserved spatial context at single-cell resolution.

The analysis of the genotoxic potential of cizolirtine, a compound being developed as a drug for analgesia and for urinary incontinence, was carried out using a battery of in vitro and in vivo assays as recommended in the guidelines for medicinal products. Negative results were obtained in an Ames test (up to 5000 µg/plate), in a Mouse Lymphoma assay (up to 2000 µg/ml) and in a single dose mouse bone marrow micronucleus assay (up to 300 mg/kg). In a human lymphocyte chromosome aberration assay, a slight statistical increase in the frequency of cells with chromosome aberrations including gaps was reported for the concentrations of 200 and 1600 μg/ml at the 24-h sampling time. This minor increase in chromosome aberrations was considered of questionable biological relevance since it was moderate, was within the laboratory historical control values, did no show a dose-dependent effect and was not observed at similar concentrations in a repeat assay. Taking into considerations the results obtained in the different in vitro and in vivo assays and a weight-of-evidence analysis, it suggests that cizolirtine would not pose a genotoxic risk when administered to humans.

Objective To determine the psychometric properties of the Person-Centered Therapeutic Relationship in Physiotherapy Scale (PCTR-PT) in order to find the most appropriate fit for the tool. Methods Patients who had received treatment at the physiotherapy service of nine hospitals in Spain were invited to complete the 31 items of the PCTR-PT scale. To select the most appropriate items of the PCTR-PT, an exploratory factorial analysis (EFA) was performed using the maximum likelihood and oblique rotation (promin) methods. Factor validity, goodness-of-fit and psychometric properties were analyzed by confirmatory factor analysis (CFA). Convergent (CFA) and discriminant validity were calculated. Internal consistency was verified using the Cronbach's alpha coefficient. The intraclass correlation coefficient (ICC) was used to examine temporal stability. Results 366 patients over 18 years old who had received, at least, 15 physiotherapy treatment sessions completed the questionnaire. The results of the exploratory factor analysis revealed a tool with 15 items in four factors [Relational Bond (N items = 4); Individualized Partnership (N items = 4); Professional Empowerment (N items = 3) and Therapeutic Communication (N items = 4)], explaining 78.4% of the variance of the total variables of this tool. The confirmatory factor analysis further confirmed the four-structure model. Reliability of the tool was approved by Cronbach's alpha in all four dimensions, as all were above .70, ranging from .84 (Individualized Partnership) to .91 (Professional Empowerment). = 0.94. Test-retest was performed with two-week intervals, indicating an appropriate stability for the scale (ICC = 0.900). Conclusion The Person-Centered Therapeutic Relationship in Physiotherapy Scale (PCTR-PT) is a useful, valid and applicable instrument to evaluate the person-centered therapeutic relationship during physiotherapy interventions. It would be interesting to investigate the predictive capacity (sensitivity and specificity) of the PCTR-PT scale.

The neurocranium changes rapidly in early childhood to accommodate the growing brain. Developmental disorders and environmental factors such as sleep position may lead to abnormal neurocranial maturation. Therefore, it is important to understand how this structure develops, in order to provide a baseline for early detection of anomalies. However, its anatomy has not yet been well studied in early childhood due to the lack of available imaging databases. In hospitals, CT is typically used to image the neurocranium when a pathology is suspected, but the presence of ionizing radiation makes it harder to construct databases of healthy subjects. In this study, instead, we use a dataset of MRI data from healthy normal children in the age range of 6 months to 36 months to study the development of the neurocranium. After extracting its outline from the MRI data, we used a conformal geometry-based analysis pipeline to detect local thickness growth throughout this age span. These changes will help us understand cranial bone development with respect to the brain, as well as detect abnormal variations, which will in turn inform better treatment strategies for implicated disorders.

Introduction Pediatric head and neck desmoid tumors are rare neoplasms that can cause significant morbidity due to infiltration of vital anatomic structures. The goal of this study is to review presentation, evaluation, and management of these tumors. Methods Retrospective study of children with head and neck desmoid tumors treated from 1999 to 2018 and literature review. Results 11 patients (5 boys, 6 girls) were included. Presentation included firm neck mass (n = 8), trismus (n = 2) and tongue lesion (n = 1). All patients had preoperative imaging with CT (n = 2), MRI (n = 1) or both (n = 8). Five patients underwent needle biopsy, five had open biopsy and one was diagnosed on pathology from primary excision. Seven patients were treated by primary surgical resection, with positive surgical margins in six cases due to proximity to vital neurovascular structures. None needed chemotherapy, had disease recurrence or progression. Three patients with unresectable disease were treated with chemotherapy. One patient was monitored with imaging without any treatment and did not have disease progression. Follow-up ranged from 6 months to 6 years (median 21 months). Ten patients (7 surgical, 2 chemotherapy, 1 observation) were either disease-free or had stable disease at last follow-up. Conclusion Pediatric head and neck desmoid tumors, though rare and histologically benign, are locally infiltrative and aggressive. When feasible, surgical treatment results in good disease control despite positive margins. A balance between achieving negative margins and minimizing functional deficits should be considered. Chemotherapy can be successfully utilized in patients where surgery entails a high risk of morbidity and mortality.

Psychological theories of emotion often highlight the dynamic quality of the affective experience, yet neuroimaging studies of affect have traditionally relied on static stimuli that lack ecological validity. Consequently, the brain regions that represent emotions and feelings as they unfold remain unclear. Recently, dynamic, model-free analytical techniques have been employed with naturalistic stimuli to better capture time-varying patterns of activity in the brain; yet, few studies have focused on relating these patterns to changes in subjective feelings. Here, we address this gap, using intersubject correlation and phase synchronization to assess how stimulus-driven changes in brain activity and connectivity are related to two aspects of emotional experience: emotional intensity and enjoyment. During fMRI scanning, healthy volunteers listened to a full-length piece of music selected to induce sadness. After scanning, participants listened to the piece twice while simultaneously rating the intensity of felt sadness or felt enjoyment. Activity in the auditory cortex, insula, and inferior frontal gyrus was significantly synchronized across participants. Synchronization in auditory, visual, and prefrontal regions was significantly greater in participants with higher measures of a subscale of trait empathy related to feeling emotions in response to music. When assessed dynamically, continuous enjoyment ratings positively predicted a moment-to-moment measure of intersubject synchronization in auditory, default mode, and striatal networks, as well as the orbitofrontal cortex, whereas sadness predicted intersubject synchronization in limbic and striatal networks. The results suggest that stimulus-driven patterns of neural communication in emotional processing and high-level cortical regions carry meaningful information with regards to our feeling in response to a naturalistic stimulus.

Cizolirtine, a substance-P and calcitonin gene-related peptide release modulator developed for the treatment of pain and urinary incontinence, was orally administered for 26-weeks to rats at dosages of 20, 60 and 200 mg/kg/day. Clinical signs were limited to post-dosing salivation and brown staining on head and muzzle. There were slight decreases in bodyweight gain and slight increases in water consumption among cizolirtine-treated animals. Slight increases in plasma alkaline phosphatase activity, and cholesterol and phospholipid concentrations were observed in mid- and/or high-dose animals. Low urinary volume, pH and sodium and potassium outputs were observed after 12-weeks, and low urinary pH, low sodium and high potassium outputs at end of treatment. Increased relative (to bodyweight) liver weight was observed in high-dose animals. Treated males and high-dose females showed a dose-related increase in the incidence and severity of periacinar hepatocytic hypertrophy and midzonal/periacinar hepatocytic fat vacuolization. Increased incidences of hepatic clear cell foci were observed in all cizolirtine-treated male groups and, to a lesser extent, in treated females. Ovaries of treated females showed a dose-dependent increased incidence of absent corpora lutea and, occasionally, follicular cysts. The dosages of 20 and 60 mg/kg/day were considered as the No-Observed-Adverse-Effect Levels for males and females, respectively.

Hyperbilirubinemia in patients with sickle cell anemia (SCA) as a result of enhanced erythrocyte destruction, lead to cholelithiasis development in a subset of patients. Evidence suggests that hyperbilirubinemia may be related to genetic variations, such as the UGT1A1 gene promoter polymorphism, which causes Gilbert syndrome (GS). Here, we aimed to determine the frequencies of UGT1A1 promoter alleles, alpha thalassemia, and β

BACKGROUND Current methods to analyze three-dimensional photography do not quantify intracranial volume, an important metric of development. This study presents the first noninvasive, radiation-free, accurate, and reproducible method to quantify intracranial volume from three-dimensional photography. METHODS In this retrospective study, cranial bones and head skin were automatically segmented from computed tomographic images of 575 subjects without cranial abnormality (average age, 5 ± 5 years; range, 0 to 16 years). The intracranial volume and the head volume were measured at the cranial vault region, and their relation was modeled by polynomial regression, also accounting for age and sex. Then, the regression model was used to estimate the intracranial volume of 30 independent pediatric patients from their head volume measured using three-dimensional photography. Evaluation was performed by comparing the estimated intracranial volume with the true intracranial volume of these patients computed from paired computed tomographic images; two growth models were used to compensate for the time gap between computed tomographic and three-dimensional photography. RESULTS The regression model estimated the intracranial volume of the normative population from the head volume calculated from computed tomographic images with an average error of 3.81 ± 3.15 percent (p = 0.93) and a correlation (R) of 0.96. The authors obtained an average error of 4.07 ± 3.01 percent (p = 0.57) in estimating the intracranial volume of the patients from three-dimensional photography using the regression model. CONCLUSION Three-dimensional photography with image analysis provides measurement of intracranial volume with clinically acceptable accuracy, thus offering a noninvasive, precise, and reproducible method to evaluate normal and abnormal brain development in young children. CLINICAL QUESTION/LEVEL OF EVIDENCE Diagnostic, V.

The high expression of brain and acute leukemia, cytoplasmic (BAALC) and ETS-related gene (ERG) has been reported to influence the outcome in acute myeloid leukemia (AML), but due to limited prospective studies, their role as prognostic factors is unclear. At diagnosis, the prognostic value of BAALC and ERG expression with respect to other cytogenetic and molecular markers was analyzed in 149 AML patients. Patients were divided into quartiles which resulted in the formation of four groups (G1-G4) based on expression values of BAALC and ERG and clinical response defined across groups. Groups with similar survival probabilities were merged together and categorized subsequently as high versus low expressers. Patients with high BAALC and ERG expression had significantly lower overall survival (OS; BAALC: p = 0.001 at 5 years 29.4% vs. 69.8%; ERG: p < 0.0001 at 5 years 4% vs. 50.4%) and disease-free survival (BAALC: p = 0.001 at 5 years 19.5% vs. 69.8%; ERG: p < 0.0001 at 5 years 4.2% vs. 47%). Patients were further stratified combining BAALC and ERG expression in an integrative prognostic risk score (IPRS). After a median follow-up of 54 months (95% CI 45-63 months) among survivors, IPRS for high versus low expressers was a significant predictor for OS (BAALC + ERG: 4% vs. 71.6%, p < 0.0001) and DFS (BAALC + ERG: 4.5% vs. 74.1%, p < 0.0001). In a multivariate model, IPRS of BAALC + ERG expression retained prognostic significance for OS (hazard ratio [HR] 2.96, 95%CI 1.91-4.59, p < 0.001) and DFS (HR 3.61, 95%CI 2.26-5.76, p < 0.001).

The effect of self-monitoring of blood glucose (SMBG) on glycemic control with regard to non-insulin-treated Type 2 diabetes mellitus (NIT-Type 2 DM) is still a controversial topic. Against this backdrop, we sought to compare the effect of a continuous short-term SMBG schema with as-usual treatment, based on changes in oral antidiabetic treatment in patients with poorly controlled Type 2 DM. We reviewed 492 NIT-Type 2 DM record charts, selecting 27 patients, with poor glycemic control, who were thought to self-monitor their blood glucose levels (SMBG group). We then compared them with 27 patients treated with modifying drugs or diets to achieve and maintain the glycemic target (Control Group). Haemoglobin A1c (HbA1c) and fasting plasma glucose (FPG) were evaluated at baseline, after 3 and 6 months. HbA1c values decreased after 3 and 6 months in the SMBG group (P < 0.001 on both occasions) and in the control group (P < 0.05 and P < 0.01, respectively), but without a significant difference between the two groups when compared at the same time. The FPG progressively decreased in both groups, reaching a significant difference in the SMBG group after 3 months and in the control group after 6 months, and without a significant difference between the two groups. The SMBG schema used in our study could be adopted for target groups before proceeding to the next therapeutic enhancement drug step, representing a useful tool that can help diabetic patients in raising awareness of and treating their disease.

Este artículo se encuentra disponible en la siguiente URL: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0228916 Objectives This study sought to develop a tool for evaluating person-centered therapeutic relationships within physiotherapy services, and to examine the content validity of the same. Methods A mixed qualitative and quantitative study was performed in three distinct phases: 1) the items were generated based on a literature review and a content analysis of focus groups of patients and physiotherapists; 2) an e-Delphi survey process was performed based on three rounds to select and refine the proposed questionnaire; 3) two rounds of cognitive interviews were conducted to evaluate the comprehension of items, the clarity of language and the appropriateness and relevance of content. Results Thirty-one items were generated based on the seven domains identified after the analysis of four focus groups of physiotherapists and four patient focus groups. Nine experts participated in the e-Delphi survey. Fifty-five patients participated in the two rounds of the cognitive pre-tests. Participating patients were from public and private physical therapy services. Based on the participants’ suggestions, four items were removed, and four were added, whereas 16 were reworded. Conclusions The final tool comprised 31 items divided into seven domains. The response format was based on a 5-point Likert frequency scale. The response options ranged from “strongly agree” to “strongly disagree”.

Objective The objective of this study was to perform a cross-cultural adaption and psychometric evaluation of the Spanish version of the Satisfaction with Epilepsy Care (SEC) questionnaire and analyze patient satisfaction with epilepsy care. Methods Transcultural adaptation and validation of the SEC were carried out using translation and back-translation with pilot testing and an expert panel. The SEC-E (Spanish) was analyzed in 213 patients with epilepsy to examine construct and criterion validity and internal consistency. Results The SEC-E achieved conceptual, semantic, and content equivalence with the original version. For content validity, one question was eliminated from the original questionnaire as it has little relevance in our cultural setting. Positive correlations for criterion validity were obtained using the gold standard measure (Satisfaction in Hospitalized Patients scale). Construct validity replicated the three dimensions of the original questionnaire. The scale showed adequate reliability through internal consistency (Cronbach's α of 0.94) and temporal stability on retest (n = 85). Patients scored (0 to 100) 77.5 [standard deviation (SD): 19.9] for satisfaction with communication, 76.9 (SD: 17) for organization, and 67.2 (SD: 22.1) for information. Significance The SEC-E is a valid and reliable tool for the assessment of educational interventions aiming to improve the quality of care in patients with epilepsy in Spanish clinical practice. The results showed a good level of patient satisfaction with epilepsy care.

INTRODUCTION Latent cranial suture fusions may present with mild or absent phenotypic changes that make the clinical diagnosis challenging. Recent reports describe patients with sagittal synostosis and a normal cranial index (CI), a condition termed normocephalic sagittal craniosynostosis (NSC). The goal of this study is to evaluate the shape and intracranial volume (ICV) in a cohort of NSC patients using quantitative cranial shape analysis (CSA). METHODS We identified 19 patients (7.5 ± 2.28 years) between 2011 and 2016, who presented to our hospital with NSC. Cranial index and CSA were measured from the computed tomography image. Cranial shape analysis calculates the distances between the patient's cranial shape and its closest normal shape. Intracranial volume was measured and compared to an established age-matched normative database. RESULTS Cranial index revealed 15 (78.9%) patients within the mesocephalic range and 4 patients (21.1%) in the brachycephalic range. Detailed CSA identified 15 (78.9%) patients with subtle phenotypic changes along the scaphocephalic spectrum (ie, subtle anterior and posterior elongation with inter-parietal narrowing) and 1 patient (5.3%) with isolated overdevelopment on the posterior part of the right parietal bone. Three patients (15.8%) had a CSA close to normal. Mean ICV was 1410.5 ± 192.77cc; most patients (78.9%) fell within ±2 standard deviations. CONCLUSION Quantitative CSA revealed that most of the patients with NSC had cranial shape abnormalities, consistent with a forme fruste scaphocephaly that could not be otherwise recognized by clinical observation or CI. Given these findings, we propose the term occult scaphocephaly to describe this condition. The associated incidence of intracranial hypertension is unknown.