Precision therapy for a medically actionable ATP1A3 variant from a genomic medicine program in an underserved population.

BACKGROUND: Genomic medicine is revolutionizing the diagnosis of rare diseases, but the implementation has not benefited underrepresented populations to the same degree. Here, we report the case of a 7-year-old boy with hypotonia, global developmental delay, strabismus, seizures, and previously suspected mitochondrial myopathy. This proband comes from an underrepresented minority and was denied exome sequencing by his public insurance. METHODS: After informed consent was obtained, buccal cells from the proband were collected and whole exome sequencing was performed. Illumina Dragen and Emedgene software was used to analyze the data at Baylor Genetics. The variants were further intepreted according to ACMG guidelines and the patient's phenotype. RESULTS: Through whole-exome sequencing (WES) under the Community Texome project, he was found to have a heterozygous de novo pathogenic variant in the ATP1A3 gene located on chromosome 19q13. CONCLUSION: In retrospect, his symptomatology matches the known medical conditions associated with the ATP1A3 gene namely Alternating Hemiplegia of Childhood 2 (AHC), a rare autosomal dominant disorder with an incidence of 1 in one million. His single nucleotide variant, (c.2401G>A, p.D801N), is predicted to be damaging. The specific amino acid change p.D801N has been previously reported in ClinVar along with the allelic variant p.D801Y and both are considered pathogenic. The identification of this variant altered medical management for this patient as he was started on a calcium antagonist and has reported no further hemiplegic episodes. This case illustrates the value of implementing genomic medicine for precision therapy in underserved populations.

Effects of a Heated Anesthesia Breathing Circuit on Body Temperature in Anesthetized Rhesus Macaques (Macaca mulatta).

This study evaluated the effects of using a heated anesthesia breathing circuit in addition to forced-air warming on body temperature in anesthetized rhesus macaques as compared with forced-air warming alone. Hypothermia is a common perianesthetic and intraoperative complication that can increase the risk of negative outcomes. Body heat is lost through 4 mechanisms during anesthesia: radiation, conduction, convection, and evaporation. Typical warming methods such as forced-air warming devices, conductive heating pads, and heated surgical tables only influence radiative and conductive mechanisms of heat loss. A commercially available heated breathing circuit that delivers gas warmed to 104 °F can easily be integrated into an anesthesia machine. We hypothesized that heating the inspired anesthetic gas to address the evaporative mechanism of heat loss would result in higher body temperature during anesthesia in rhesus macaques. Body temperatures were measured at 5-min intervals in a group of 10 adult male rhesus macaques during 2 anesthetic events: one with a heated anesthesia breathing circuit in addition to forced-air warming, and one with forced-air warming alone. The addition of a heated breathing circuit had a significant positive effect on perianesthetic body temperature, with a faster return to baseline temperature, earlier nadir of initial drop in body temperature, and higher body temperatures during a 2-h anesthetic procedure. Use of a heated anesthesia breathing circuit should be considered as a significant refinement to thermal support during macaque anesthesia, especially for procedures lasting longer than one hour.

Mid-Tibiofibular Amputation as a Method of Terminal Blood Collection in Xenopus Laevis.

The African clawed frog, Xenopus laevis, is a widely used model for biomedical research. X. laevis could be more useful as a model with a better method for collection and analysis of its blood and serum. However, blood collection in X. laevis can be challenging due to their small size, lack of peripheral vascular access, and species-specific hematology variables. The goal of this study was to compare cardiocentesis, the current gold standard terminal blood collection method, with a leg amputation technique. Blood samples were collected from 24 laboratory-reared X. laevis, randomized to either the cardiocentesis or leg amputation method, with 6 males and 6 females in each group. Hematology and serum biochemistry were also conducted to identify any lymph contamination in the samples. The leg amputation method produced significantly higher blood volumes in shorter times and showed no significant differences in clinical pathology parameters as compared with cardiocentesis. These results indicate that blood collection by leg amputation may be a valuable approach for increasing the utility of an already valuable biomedical research model.

Physics-guided neural network for predicting chemical signatures.

Achieving high classification accuracy on trace chemical residues in active spectroscopic sensing is challenging due to the limited amount of training data available to the classifier. Such classifiers often rely on physics-based models for generating training data though these models are not always accurate when compared to measured data. To overcome this challenge, we developed a physics-guided neural network (PGNN) for predicting chemical reflectance for a set of parameterized inputs that is more accurate than the state-of-the-art physics-based signature model for chemical residues. After training the PGNN, we use it to generate a library of predicted spectra for training a classifier. We compare the classification accuracy when using this PGNN library versus a library generated by the physics-based model. Using the PGNN, the average classification accuracy increases from 0.623 to 0.813 on real chemical reflectance data, including data from chemicals not included in the PGNN training set.

Commissioning of high current H+/D+ ion beams for the prototype accelerator of the International Fusion Materials Irradiation Facility.

The Linear IFMIF (International Fusion Materials Irradiation Facility) Prototype Accelerator (LIPAc) is aiming at demonstrating the low energy section of a 40 MeV/125 mA IFMIF deuteron accelerator up to 9 MeV with a full beam current in cw operation. For such a high-power beam, the LIPAc injector is required to produce a 100 keV D+ beam with 140 mA and match it for injection into the Radio Frequency Quadrupole (RFQ) accelerator. The injector is designed by CEA-Saclay based on the high intensity light ion source (SILHI). In 2019, the commissioning of the RFQ to demonstrate the D+ beam acceleration at a low duty cycle (0.1%) was conducted. A nominal beam current of 125 mA D+ beam was accelerated up to 5 MeV through the RFQ successfully. The LIPAc injector fully satisfied the requirements for RFQ beam commissioning at the pulse mode.

Effect of Home Cage Bedding in the Induction Chamber on Serum Cortisol and Corticosterone Levels in Response to Isoflurane-induced Anesthesia in C57BL/6J Mice.

Mice are routinely anesthetized with isoflurane in an induction chamber. The AVMA Guidelines for the Euthanasia of Animals states that distress should be minimized during euthanasia but does not address this point in regard to induction of anesthesia. Here we evaluated the potential for familiar surroundings to reduce the adrenocortical response of mice during anesthesia induction with isoflurane. However, adding bedding from the animals' home cage to the induction chamber failed to significantly reduce serum cortisol or corticosterone levels in male and female C57BL/6J mice. These results indicate that familiar surroundings do not appear sufficient to reduce the adrenocortical response of mice during anesthesia induction with isoflurane.

Nanosilicalites as Support for ß-Glucosidases Covalent Immobilization.

Many different materials have been tested for ß-glucosidases immobilization. Such materials, however, often show a poor activity related to a low surface area of the support or even enzyme hindrance caused by entrapment inside porous matrix. In this context, the use of nanosized zeolites as enzymes support is quite new and may be an interesting alternative. The present work evaluates the immobilization of ß-glucosidases in nanosized silicalites by covalent coupling. The new biocatalyst was able to convert 100% of cellobiose into glucose in 18 h at 50 °C and pH 5, retaining 85% of its activity after five cycles of reuse. A detailed investigation of the published literature indicates that, apparently, this is the first work concerning the immobilization of ß-glucosidases on nanosized zeolites ever reported.

Operation and commissioning of IFMIF (International Fusion Materials Irradiation Facility) LIPAc injector.

The objective of linear IFMIF prototype accelerator is to demonstrate 125 mA/CW deuterium ion beam acceleration up to 9 MeV. The injector has been developed in CEA Saclay and already demonstrated 140 mA/100 keV deuterium beam [R. Gobin et al., Rev. Sci. Instrum. 85, 02A918 (2014)]. The injector was disassembled and delivered to the International Fusion Energy Research Center in Rokkasho, Japan. After reassembling the injector, commissioning has started in 2014. Up to now, 100 keV/120 mA/CW hydrogen and 100 keV/90 mA/CW deuterium ion beams have been produced stably from a 10 mm diameter extraction aperture with a low beam emittance of 0.21 π mm mrad (rms, normalized). Neutron production by D-D reaction up to 2.4 × 10(9) n/s has been observed in the deuterium operation.

Circumstances surrounding deaths from the perspective of bereaved Honduran families.

PURPOSE: This qualitative study examined how bereaved individuals from Honduras responded to deaths of loved ones, particularly through exploring circumstances surrounding deaths and various coping strategies. METHODS: With the help of a translator, bereaved family members in Honduras were interviewed using a semi-structured format. The interactions were audio-recorded and later translated and transcribed. RESULTS: Some 60% of individuals spent time with other family members during their loved one's end of life and 22.5% of grieving individuals took solace in spirituality or religious practices and connecting with God. Some 40% wanted to speak with others through support groups. When individuals spoke about remembering the deceased, both comforting and discomforting effects were expressed. CONCLUSIONS: Further research is needed to learn more about coping strategies in various cultures and support mechanisms that health professionals can use or suggest when working with bereaved individuals.

Antidepressants for older people: what can we learn from the current evidence base?

This paper updates our previous review of the evidence base for managing depression in old age while focusing more specifically on the use of antidepressants. Overall, recent systematic reviews and meta-analyses indicate that antidepressants are effective in the acute treatment of depression in old age but that the superiority of active drug over placebo is quite modest. The depression of Alzheimer's disease is probably not treated effectively with antidepressants. The most consistent evidence is for the effectiveness of continued antidepressant treatment in those depressed patients who respond well to acute treatment. There remains a clear need for more research to identify effective treatments for resistant depression though therapeutic nihilism should be avoided if first-line treatment fails.

International Fusion Materials Irradiation Facility injector acceptance tests at CEA/Saclay: 140 mA/100 keV deuteron beam characterization.

In the framework of the ITER broader approach, the International Fusion Materials Irradiation Facility (IFMIF) deuteron accelerator (2 × 125 mA at 40 MeV) is an irradiation tool dedicated to high neutron flux production for future nuclear plant material studies. During the validation phase, the Linear IFMIF Prototype Accelerator (LIPAc) machine will be tested on the Rokkasho site in Japan. This demonstrator aims to produce 125 mA/9 MeV deuteron beam. Involved in the LIPAc project for several years, specialists from CEA/Saclay designed the injector based on a SILHI type ECR source operating at 2.45 GHz and a 2 solenoid low energy beam line to produce such high intensity beam. The whole injector, equipped with its dedicated diagnostics, has been then installed and tested on the Saclay site. Before shipment from Europe to Japan, acceptance tests have been performed in November 2012 with 100 keV deuteron beam and intensity as high as 140 mA in continuous and pulsed mode. In this paper, the emittance measurements done for different duty cycles and different beam intensities will be presented as well as beam species fraction analysis. Then the reinstallation in Japan and commissioning plan on site will be reported.

New generation multi-modal antidepressants: focus on vortioxetine for major depressive disorder.

Vortioxetine is a novel antidepressant with effects on multiple 5-HT receptors and on the serotonin transporter. This paper reviews preclinical and clinical evidence regarding its mechanism of action, its tolerability, and its efficacy in treating major depression. Clinical studies indicate that vortioxetine is effective in the treatment of major depression, though there is no suggestion of superiority over active comparators. There may be a clinically meaningful advantage in terms of tolerability.

Adult sedentary behavior: a systematic review.

CONTEXT: While the health benefits of meeting moderate/vigorous-intensity physical activity (MVPA) guidelines have been well established, the health risks of sedentary behavior, independent of meeting MVPA guidelines, are becoming evident. Sedentary behavior may require different interventions, based on correlates that differ from MVPA. The current review aimed to collect and appraise the current literature on correlates of sedentary behaviors among adults. EVIDENCE ACQUISITION: Papers were considered eligible if they were published in English-language peer-reviewed journals and examined correlates of sedentary behaviors. Literature searches were conducted in August 2011 among ten search engines yielding 3691 potentially relevant records; of these, 109 papers (82 independent samples) passed eligibility criteria. EVIDENCE SYNTHESIS: Articles included were published between 1982 and 2011, with sample sizes ranging from 39 to 123,216. Eighty-three were cross-sectional, 24 followed a prospective design, one was experimental baseline data, and one was cohort design. Sedentary behavior was primarily measured as TV viewing or computer use, followed by analysis of a more omnibus assessment of time spent sitting. Evidence was present for sedentary behavior and correlates of education, age, employment status, gender, BMI, income, smoking status, MVPA, attitudes, and depressive symptoms/quality of life. Notable differences by specific sedentary behaviors were present that aided in the explanation of findings. CONCLUSIONS: Results point to the high specificity of various sedentary behaviors (e.g., TV viewing vs sitting and socializing), suggesting that the research domain is complex and cannot be considered the simple absence of MVPA. Several sociodemographic and health factors appear reliably linked to sedentary behavior, yet there is an obvious absence of research focused on cognitive, social, and environmental factors that could be of use in anti-sedentary behavior interventions.

Estudio comparativo de la prevalencia de la infección por Helicobacter Pylori entre el personal sanitario de dos servicios hospitalarios. La pertenecía al área de digestivo como factor predisponente / Comparative study of prevalence of Helicobacter Pylori infection among the nursing staff in two hospital services. Belonging to the gastroenterology service as a predisposing factor

Objetivos. Estudiar la prevalencia de la infección por Helicobacter pylori en el personal sanitario de dos Servicios hospitalarios del Hospital Clínico San Cecilio de Granada. Casuística. Se estudian 60 personas; 30 de ellas del Servicio de Aparato Digestivo (personal facultativo y no facultativo ) y otras 30 de personal de los Servicios de Oftalmología y endocrinología. Métodos. Se empleo el test del aliento con urea marcada con C13 (no radiactivo). UB test. Resultados: En el personal del Servicio Digestivo la posibilidad del test fue del 65,5% (19 casos) y en los Servicios no digestivos del 73% (19 casos); no hubo diferencias estadísticamente significativas entre ellos. Según el tipo de personal las proporciones fueron en el Servicio de Digestivo: médicos adjuntos 68,4% (13 casos+), médicos residentes, 50% (7 casos+) ayudantes técnicos sanitarios 75% (9 casos+) y personal auxiliar 90% (9 casos+). Hubo diferencias estadísticas significativas (p<0.05) entre el personal auxiliar y los médicos adjuntos y personal auxiliar y médicos residentes. Conclusiones. La prevalencia de la infección por Helicobacter pylori en el Servicio de Aparato Digestivo es del 69,1% similar a la de otros servicios del Hospital. El personal del Servicio de Aparato Digestivo es el más expuesto a la infección por Helycobacter pylori, que es el más expuesto al contacto directo con los pacientes

Objetives: To study the infection due to Helicobacter pylori among the health personnel in two hospital services at the University Hospital San Cecilio in Granada, Spain.Casuistry. A total of 60 individuals were studied; 30 of them belonged to the Gastroenterology Unit (medical and nonmedical staff) and 30 belonged to the Endocinology and the Ophthalmology Units. Methods. The Carbon 13- labeled urea breath test (non radioactive) (C-13 UBT) was used. Results. Among the staff from the Gastroenterology Unit, the positive result of the test was 65% (19 cases), while it was 73% among the personnel from the other two Units (19 cases). There were no statistically significant differences among them. In the Gastroenterology Unit, the ratios were as follows: attending physicians, 68% (13 cases +); resident physicians , 50% (7 cases +); nursing assistant, 75% (9 cases +); and assistant staff, 90% (9 cases +). There were statistically significant differences (p< 0.05) between the assistant staff and the attending physicians and the assistant staff and the resident physicians. Conclusions. Prevalence of Helicobacter pylori infection in the Gastroenterology Unit is similar to other hospitals (69.1%). The assistant staff in the Gastroenterology Unit is the most exposed to infection by Helicobacter pylori due to the direct contact with the patient

Densidad mineral ósea y remodelado ósea en mujeres posmenopáusicas con cirrosis hepática vírica / Bone Mineral density an bone remodeling in postmenopausal women with liver cirrohosis with viral origin

Introducción. Se conoce que la cirrosis hepática, tanto vírica como alcohólica, provoca pérdida de masa ósea en hombres. Sin embargo, poco se conoce del efecto de la cirrosis hepática sobre la masa ósea y remodelado óseo de mujeres posmenopáusicas con cirrosis vírica. Igualmente, se desconoce si realmente empeora aún más la masa ósea, ya deteriorada, de estas mujeres. Objetivo: Nuestro objetivo fue estudiar la masa ósea, remodelado óseo y factores hormonales relacionados con el metabolismo óseo en 49 mujeres con cirrosis hepática de etiología vírica y 22 controles sanas. Resultados: La ingesta etílica era inferior a 30 g a la semana. En todas ellas, se midió la densidad mineral ósea (DMO) entre las pacientes cirróticas y controles sanas (expresadas como Z-score) en LS (-0,13±0,025 vs 0,17±1,18; p<0,3) y FN (0,15±1,17 vs. 0,01±1,10; p<0,6). Las concentraciones séricas de estradiol eran más elevadas en mujeres con cirrosis que en las sanas (11,89±15,64 ng/ml vs. 6,54±5,30 ng/ml; p<0,04), existiendo una correlación positiva entre los valores séricos de estradiol y la gravedad de la cirrosis (r=0,49; p<0,001), Además, existía una correlación inversa entre los valores séricos de FSH y DMO (r= -0,31; p<0,03) y positiva de SHBG con la DMO (r=0.48; p<0,03), e inversa entre los valores de SHBG y estradiol (r=-0,29; p<0,05). Los valores séricos de insulina eran significativamente más elevados en las pacientes cirróticas (20,94 ± 15,21 µU/ml) que en los controles (12,96 ± 10,96 µU/ml); p<0,02 y había correlación positiva entre la insulinemia y la DMO (r=0,40; p<0,02) en pacientes cirróticas.Conclusiones: Los parámetros bioquímicos de remodelado óseo mostraban alto turnover, tanto en pacientes como en controles sin diferencias entre ellas. Nuestros hallazgos muestran que las mujeres posmenopáusicas con cirrosis hepática vírica no presentan mayor pérdida de masa ósea que las mujeres posmenopáusicas sanas. A ello, parece contribuir los niveles séricos elevados de estradiol e insulina que presentan las pacientes. No hay diferencias en el remodelado óseo, que es de alto turnover, tanto en las pacientes como en los controles

Introduction: Liver cirrohosis both with viral and alcoholic origin causes bone mass loss in males. However, the effect of liver cirrohosis on bone mass and bone remodeling in postmenopausal women with liver cirrhosis with viral origin is little know. Likewise, it is not known if it worsens even more the already damaged bone mass of these women. Aim: Our aim was to study the bone mass, bone remodeling, and other hormonal factors related to bone metabolism in 29 women with liver cirrhosis of viral etiology and 22 healthy controls. Results: Alcohol consumption was below 30g/week. Bone mineral density (BMD) was measured by dual x-ray absorptiometry in the lumbar spine (LS) and the femoral week (FN) in all the patients. Significant differences in BMD were not found between cirrhotic patients and healthy controls (expressed as Z-score) in LS (-0,13±0.025 vs. 0,17±1,18; p<0.3) and FN (0,15±1.17 vs. 0.01±1.10; p<0.6). Serum estradiol concentrations were higher in the cirrohotic women than in the healthy ones (11.89±15.64 ng/ml vs. 6.54±5.30ng/ml; p<0,04), being a positive correlation between the serum estradiol values and the cirrhosis seriousness (r=0,49; p<0.001) Besides, there was an opposite correlation between the serum values of FSM and BMD (r=0.31; p<0.03); a positive correlation of SHBG and BMD (r=0,48; p<0,03); and an opposite correlation between SHBG and estradiol values (r=-0.29; p<0.05). Serum insulin values were significantly higher in the cirrohotic patients (20.94±15.21 µU/ml) than in the controls (12.06±10.96 µU/ml), (p<0.02). There was a positive correlation between insulinemia and BMD in cirrhotic patients (r=0.40; p<0.02). Conclusion: Biochemical parameters of bone remodeling showed a high turnover both in patients and controls without differences between them. Our finds show postmenopausal women with liver cirrhosis with viral origin do not have a higher bone mass loss than healthy postmenopausal women do. The high serum insulin and serum estradiol levels seem to contribute to it. There are no differences in bone remodeling, which shows a high turnover both in patients and controls

An opioid screening instrument: long-term evaluation of the utility of the Pain Medication Questionnaire.

The Pain Medication Questionnaire (PMQ) was designed to assess the risk for opioid medication misuse in chronic pain patients. A preliminary study showed a positive relationship between higher PMQ scores and concurrent measures of substance abuse, psychopathology, and physical/life-functioning. Using a larger sample size, the present study sought to replicate these findings, and to expand upon them by examining the relationship between PMQ scores and various treatment outcomes. The PMQ was administered to 271 newly evaluated chronic pain patients who were subsequently re-evaluated immediately post-treatment, as well as six months following discharge. Subgroups were then formed according to the lowest (L-PMQ), middle (M-PMQ), and highest (H-PMQ) one-third of PMQ total scores. It was found that the H-PMQ group was 2.6 times more likely to have a known substance-abuse problem, 3.2 times more likely to request early refills of prescription medication, and 2.3 times more likely to drop out of treatment, as compared to the L-PMQ group. They also had diminished biopsychosocial functioning. In addition, at six months following discharge, patients who completed the program experienced a significant decrease in PMQ scores over time relative to those patients who were unsuccessfully discharged from the program or who dropped out. This study represents the second stage in the development of a psychometrically sound screening tool for measuring risk for opioid medication misuse among chronic pain patients, and findings suggest the long-term utility of the PMQ in identifying patients who are more likely to complete and benefit from a pain management program.

[Eosinophilic enteritis as a rare cause of ascites]. / Enteritis eosinofílica como causa infrecuente de ascitis.

Eosinophilic gastroenteritis is an infrequent entity characterized by tissular eosinophilia that can affect different layers of the intestinal wall. This entity can affect any area of the digestive apparatus from the esophagus to the rectum. Clinical manifestations depend on the affected layers and range from barely perceptible symptoms to intestinal obstruction or ascites. We present the case of an 18-year-old woman who showed abdominal ascites as a rare form of presentation with difficult differential diagnosis with peritoneal carcinomatosis.