Histerectomía laparoscópica en patología benigna en un hospital universitario terciario. Análisis y evolución de un periodo de 8 años / Laparoscopic hysterectomy for benign pathology in a tertiary university hospital: Analysis and evolution in a period of 8 years

Objetivo: Reflexionar desde el análisis de los datos del número de histerectomías laparoscópicas que puede realizar cada miembro de un servicio de ginecología de un hospital terciario sobre la conveniencia de limitar este procedimiento a un número limitado de profesionales. Material y métodos: Estudio retrospectivo, descriptivo, sobre las histerectomías realizadas por cualquier indicación en nuestro hospital en el periodo comprendido entre el 1 de mayo del año 2014 y el 30 de abril del año 2022. Resultados: En este periodo hemos realizado 1548 histerectomías, de las que 760 se efectuaron por vía laparoscópica; y de ellas, 289 fueron indicadas por patología benigna. Considerando el total de profesionales que conforman el pool de cirujanos que realizan cirugía por patología benigna, la media de histerectomías laparoscópicas por cirujano y año sería de 1,4 casos. Conclusiones: Para garantizar la adecuada calidad de la cirugía, el número de profesionales que realizan histerectomías laparoscópicas en un hospital terciario debe ser limitado.(AU)

Objective: To reflect from the analysis of the data of the number of laparoscopic hysterectomies that each member of a gynaecology service of a tertiary hospital can perform on the convenience of limiting this procedure to a limited number of professionals. Material and methods: Retrospective, descriptive study on hysterectomies performed for any indication in our hospital in the period between May 1, 2014 and April 30, 2022. Results: In this period, we have performed 1548 hysterectomies of which 760 were performed laparoscopically and of these, 289 were indicated for benign pathology. Considering the total number of professionals that make up the pool of surgeons who perform surgery for benign pathology, the average number of laparoscopic hysterectomies per surgeon per year would be 1.4 cases. Conclusions: To ensure adequate quality of surgery, the number of professionals performing laparoscopic hysterectomies in a tertiary hospital should be limited.(AU)

[Translated article] A systematic review of the literature: The use of metaphyseal sleeves in revision total knee arthroplasty.

BACKGROUND AND OBJECTIVES: The purpose of this study is to analyse the indications, complications, survivorship and clinical/functional outcome of metaphyseal sleeves as a treatment option in revision total knee arthroplasty. MATERIAL AND METHOD: A systematic review was made following the PRISMA recommendations on the use of metaphyseal sleeves for revision total knee arthroplasty. We included prospective and retrospective studies published in the last 10 years looking at implant survivorship, clinical and functional outcome with a minimum follow-up of 2 years. RESULTS: The included studies showed good both functional and clinical outcomes. The overall reoperation rate was 16.2%, with an overall survival rate of 92.2% and aseptic survivorship of 98.2%. CONCLUSIONS: Metaphyseal sleeves are a good treatment option for this surgery, especially in AORI II or III type bone defects, achieving good intraoperative and primary stability of the implant, with good and rapid osseointegration.

A systematic review of the literature: The use of metaphyseal sleeves in revision total knee arthroplasty. / Una revisión sistemática de la literatura: el uso de vainas metafisarias en cirugía de revisión de artroplastia de rodilla.

BACKGROUND AND OBJECTIVES: The purpose of this study is to analyze the indications, complications, survivorship and clinical/functional outcome of metaphyseal sleeves as a treatment option in revision total knee arthroplasty. MATERIAL AND METHOD: A systematic review was made following the PRISMA recommendations on the use of metaphyseal sleeves for revision total knee arthroplasty. We included prospective and retrospective studies published in the last 10 years looking at implant survivorship, clinical and functional outcome with a minimum follow-up of 2 years. RESULTS: The included studies showed good both functional and clinical outcomes. The overall reoperation rate was 16.2%, with an overall survival rate of 92.2% and aseptic survivorship of 98.2%. CONCLUSIONS: Metaphyseal sleeves are a good treatment option for this surgery, especially in AORI II or III type bone defects, achieving good intraoperative and primary stability of the implant, with good and rapid osseointegration.

Air pollution relevance analysis in the bay of Algeciras (Spain).

The aim of this work is to accomplish an in-depth analysis of the air pollution in the two main cities of the Bay of Algeciras (Spain). A large database of air pollutant concentrations and weather measurements were collected using a monitoring network installed throughout the region from the period of 2010-2015. The concentration parameters contain nitrogen dioxide (NO2), sulphur dioxide (SO2) and particulate matter (PM10). The analysis was developed in two monitoring stations (Algeciras and La Línea). The higher average concentration values were obtained in Algeciras for NO2 (28.850 µg/m3) and SO2 (11.966 µg/m3), and in La Línea for PM10 (30.745 µg/m3). The analysis shows patterns that coincide with human activity. One of the goals of this work is to develop a useful virtual sensor capable of achieving a more robust monitoring network, which can be used, for instance, in the case of missing data. By means of trends analysis, groups of equivalent stations were determined, implying that the values of one station could be substituted for those in the equivalent station in case of failure (e.g., SO2 weekly trends in Algeciras and Los Barrios show equivalence). On the other hand, a calculation of relative risks was developed showing that relative humidity, wind speed and wind direction produce an increase in the risk of higher pollutant concentrations. Besides, obtained results showed that wind speed and wind direction are the most important variables in the distribution of particles. The results obtained may allow administrations or citizens to support decisions.

Air pollution and meteorological variables' effects on COVID-19 first and second waves in Spain.

The aim of this research is to study the influence of atmospheric pollutants and meteorological variables on the incidence rate of COVID-19 and the rate of hospital admissions due to COVID-19 during the first and second waves in nine Spanish provinces. Numerous studies analyze the effect of environmental and pollution variables separately, but few that include them in the same analysis together, and even fewer that compare their effects between the first and second waves of the virus. This study was conducted in nine of 52 Spanish provinces, using generalized linear models with Poisson link between levels of PM10, NO2 and O3 (independent variables) and maximum temperature and absolute humidity and the rates of incidence and hospital admissions of COVID-19 (dependent variables), establishing a series of significant lags. Using the estimators obtained from the significant multivariate models, the relative risks associated with these variables were calculated for increases of 10 µg/m3 for pollutants, 1 °C for temperature and 1 g/m3 for humidity. The results suggest that NO2 has a greater association than the other air pollution variables and the meteorological variables. There was a greater association with O3 in the first wave and with NO2 in the second. Pollutants showed a homogeneous distribution across the country. We conclude that, compared to other air pollutants and meteorological variables, NO2 is a protagonist that may modulate the incidence and severity of COVID-19, though preventive public health measures such as masking and hand washing are still very important. Supplementary Information: The online version contains supplementary material available at 10.1007/s13762-022-04190-z.

Sociocultural influences on dietary behavior and meal timing among Native Hawaiian and Pacific Islander women at risk of endometrial cancer: a qualitative investigation.

PURPOSE: Determine sociocultural influences on dietary behavior, body image, weight loss, and perceptions of the cultural appropriateness of a meal-timing intervention design and menu among Native Hawaiian and Pacific Islander (NHPI) women at risk of endometrial cancer. METHODS: Six 90-min videoconference focus groups among NHPI women (n = 35) recruited by a community champion in Utah. Eligible women were aged ≥ 18 years at risk of endometrial cancer (i.e., BMI ≥ 25 kg/m2, history of non-insulin-dependent diabetes or complex atypical endometrial hyperplasia) had a working cell phone capable of downloading a phone app, could use their cell phone during the day, and were not night-shift workers. Twelve semi-structured questions were posed during the focus groups. Using inductive qualitative methods based on Hatch's 9-step approach, de-identified transcript data were analyzed. RESULTS: Overarching themes included economic factors, cultural influences, meal choice and timing, and perceptions of health. Subthemes included affordability, waste avoidance, inundated schedules, and cultural influences. Perceptions of body size and weight loss were influenced by family, community, and social media, whose messages could be conflicting. Important intervention components included satisfying, convenient pre-made meals, while barriers included the need to cook for family members. CONCLUSIONS: Dietary interventions targeting metabolic health among NHPI women should consider the multitude of sociocultural and economic factors that influence food choices and meal timing in this population, including affordability, hectic schedules, and immigrant adjustment. Promoting the link between physical and mental well-being as opposed to weight loss is a key approach to reaching this population.

Pan-tumor landscape of fibroblast growth factor receptor 1-4 genomic alterations.

BACKGROUND: Selective tyrosine kinase inhibitors targeting fibroblast growth factor receptor (FGFR) 1-4 genomic alterations are in development or have been approved for FGFR-altered cancers (e.g. bladder cancer and advanced intrahepatic cholangiocarcinoma). Understanding FGFR inhibitor-resistance mechanisms is increasingly relevant; we surveyed the pan-tumor landscape of FGFR1-4 genomic alterations [short variants (SVs), gene rearrangements (REs), and copy number alterations (CNAs)], including their association with tumor mutational burden (TMB) and the genomic comutational landscape. PATIENTS AND METHODS: Comprehensive genomic profiling of 355 813 solid tumor clinical cases was performed using the FoundationOne and FoundationOne CDx assays (Foundation Medicine, Inc.) to identify genomic alterations in >300 cancer-associated genes and TMB (determined on ≤1.1 megabases of sequenced DNA). RESULTS: FGFR1-4 SVs and REs occurred in 9603/355 813 (2.7%), and CNAs in 15 078/355 813 (4.2%) samples. Most common FGFR alterations for bladder cancer, intrahepatic cholangiocarcinoma, and glioma were FGFR3 SVs (1051/7739, 13.6%), FGFR2 REs (618/6641, 9.3%), and FGFR1 SVs (239/11 550, 2.1%), respectively. We found several, potentially clinically relevant, tumor-specific associations between FGFR1-4 genomic alterations and other genomic markers. FGFR3 SV-altered bladder cancers and FGFR1 SV-altered gliomas were significantly less likely to be TMB-high versus unaltered samples. FGFR3 SVs in bladder cancer significantly co-occurred with TERT and CDKN2A/B alterations; TP53 and RB1 alterations were mutually exclusive. In intrahepatic cholangiocarcinoma, FGFR2 REs significantly co-occurred with BAP1 alterations, whereas KRAS, TP53, IDH1, and ARID1A alterations were mutually exclusive. FGFR1 SVs in gliomas significantly co-occurred with H3-3A and PTPN11 alterations, but were mutually exclusive with TERT, EGFR, TP53, and CDKN2A/B alterations. CONCLUSIONS: Overall, our hypothesis-generating findings may help to stratify patients in clinical trials and guide optimal targeted therapy in those with FGFR alterations.

Epidemiology of Bone Fractures in the Hand in Adult Population Using the ICD-10 Classification.

PURPOSE OF THE STUDY The purpose of this study was to conduct an epidemiological study of hand fractures in adult population. MATERIAL AND METHODS A retrospective observational study in a population of 470,000 habitants was performed. Over the course of three years, all patients over 16 years of age who were diagnosed with fracture or fracture-dislocation at the level of a carpal bone, metacarpal and/or phalange were included. These fractures were classified according to the International Classification of Diseases 10th edition (ICD-10). Incidence rates, along with gender and age distribution were also studied. RESULTS 1,267 patients with a total of 1,341 hand fractures were included. They represented 29.7% of all upper limb fractures and 7.6% of all traumatological emergencies involving a bone fracture during that period. The most frequent ICD-10 group was S62.3, with the fifth metacarpal as the most often affected bone (39.7%). The most frequent location at the level of the phalanges (S62.5) was the proximal third of the proximal phalanx of the fifth radius. The global incidence rate was 99 fractures per 100,000 persons/year. No seasonal variation was observed. Only 10.2% of hand fractures received surgical treatment. DISCUSSION Several epidemiological studies have been published on fractures in the hand, but none have used the ICD-10 classification. Although the distribution of our stratified sample by age and gender was similar to those previously published, the incidence rate in our study was much lower. We may possibly extrapolate our results to the rest of the Spanish population and even to the rest of the population of southern Europe, given the scarcity of epidemiological studies on this matter in these geographical areas. CONCLUSIONS The ICD-10 classification is useful for the description and classification of hand fractures. The most often affected group is that including metacarpals of the long fingers (S62.3), being the distal level of the fifth metacarpal in young male patients the most frequent one. Most fractures are treated conservatively and in case of surgical treatment, the preferred surgical techniques include K-wire fixation, interfragmentary compression screws and plate osteosynthesis. Key words: epidemiology, incidence, fracture, fracture dislocation, carpal bones, metacarpals, finger phalanges.

Psychosocial and biological predictors of resident physician burnout.

BACKGROUND: A high proportion of health professionals in training suffer from work-related stress and may develop a burnout syndrome. OBJECTIVES: To study the incidence of burnout after the first year of residency in a teaching hospital and to identify baseline psychological, psychosocial work conditions, and biological risk factors. METHODOLOGY: We assessed the following in a prospective cohort of residents at baseline (first month residence) and after 1 year: background factors (socio-demographics, psychiatric history), perceived stress score (Perceived Stress Scale), Maslach Burnout Inventory score, and psychosocial factors (Job Content Questionnaire). Blood samples were obtained to study serum cortisol, IL-6, and TNF-α concentrations. The cumulative incidence was modelled by multivariate log-binomial regression analysis. RESULTS: We included 71 participants with a female majority (64.8%), age 26.4 (2.65) years, psychiatric history in 20%, and burnout in 13%. Among those without burnout initially (N = 59), it had developed by 1 year in 22% of residents. Increased job demand (RR = 1.259, 95%CI = 1.019-1.556, p = 0.033) and decreased cortisol levels (RR = 0.877, 95%CI = 0.778-0.989, p = 0.032) predicted burnout after 1 year of residency among medical trainees. CONCLUSION: Burnout syndrome develops in 22% of residents by 1 year of training and can be predicted by increased work demands and decreased cortisol levels.

Phosphaturic Mesenchymal Tumor.

Phosphaturic mesenchymal tumors (PMTs) are neoplasms associated with tumor-induced osteomalacia. Patients typically present with pathologic fractures in the setting of chronic hypophosphatemic hyperphosphaturic osteomalacia, as well as gradual muscle weakness, bone pain, and difficulty walking. Because of their rarity and nonspecific symptomatology, phosphaturic mesenchymal tumors often go undiagnosed for years. Even when discovered on imaging, the tumors can be diagnostically challenging for radiologists. Phosphaturic mesenchymal tumors often tend to be small and can be located nearly anywhere in the body, and, therefore, can mimic many other tumors. This case highlights the imaging and pathologic markers of a phosphaturic mesenchymal tumor, often found in a patient with tumor-induced osteomalacia.

Neumomediastino: una complicación frecuente de neumonía COVID-19 / Pneumomediastinum: a frequent complication of covid-19 pneumonia

Introducción: El neumomediastino es una complicación en pacientes con COVID-19, ocasionado en el contexto de un proceso inflamatorio importante. Metodología: Se realizó un estudio descriptivo, retrospectivo y transversal. Se revisaron las tomografías de tórax e historias clínicas de pacientes con y sin diagnóstico de COVID-19 entre el 1 de abril y el 30 de julio de 2020. Resultados: Se identificaron 66 pacientes con neumomediastino y diagnóstico de COVID-19. La prevalencia encontrada fue de 3,2%, el 81,8% correspondía al sexo masculino, la edad promedio fue 53,4 años, el tiempo de estancia media hospitalaria fue de 22,98 días, las comorbilidades más frecuentes fueron la obesidad, diabetes e hipertensión arterial. El 95,5% no reportó tabaquismo y el 89,4% no estuvo en ventilación mecánica. Los síntomas más frecuentes fueron la disnea, tos no productiva y dolor torácico. El 69,7% de pacientes tuvieron desenlace fatal. En la tomografía pulmonar se evidenció que el 43,9% presentó neumomediastino de grado moderado, y respecto al compromiso pulmonar el 97% presentó un patrón típico bilateral, el estadio evolutivo pico y progresivo se presentó en 56,1% y 31,8% respectivamente y el porcentaje de afectación pulmonar más frecuente fue el grave (53%). Un porcentaje de afectación pulmonar mayor al 50% se correlacionó directamente con la gravedad del neumomediastino (p<0,05). La ferritina promedio fue 884,58 ug/ml, dímero D 5,1 mg/ml, DHL 595,55 UI/L, PCR 150,7 mg/L, linfocitos 825,1 c/mm3, ácido láctico 1,99 mmol/L, PCT 0,78 ng/ml, IL6 313 pg/ml y PaFiO2 171,5 mmHg. Conclusión: El neumomediastino espontáneo es una complicación frecuente en pacientes con COVID-19, siendo un indicador de mala evolución.(AU)

Introduction: Pneumomediastinum is a frequent complication in patients with COVID-19, caused in the context of a major inflammatory process. Methodology: A descriptive, retrospective and cross-sectional study was conducted. We reviewed the chest CT scans and medical records of patients with/without a diagnosis of COVID-19 between April 1 and July 30, 2020. Results: We identified 66 patients with pneumomediastinum and a diagnosis of COVID-19. The prevalence found was 3.2%, 81.8% corresponded to males, the average age was 53.4 years, the average length of stay in hospital was 22.98 days, the most frequent comorbidities were obesity, diabetes and hypertension. 95.5% did not report smoking and 89.4% were not on mechanical ventilation. The most frequent symptoms were dyspnea, non-productive cough and chest pain. 69.7% of patients had a fatal outcome. Pulmonary tomography showed that 43. 9% presented moderate grade pneumomediastinum and with respect to pulmonary involvement 97% presented a typical bilateral pattern, the peak and progressive stage presented in 56.1% and 31.8% respectively and the most frequent percentage of pulmonary involvement was severe (53%). A percentage of lung involvement higher than 50% correlated directly with the severity of the pneumomediastinum (p<0.05). The average ferritin was 884.58 ug/ml, D-dimer 5.1 mg/ml, DHL 595. 55 IU/L, PCR 150.7 mg/L, lymphocytes 825.1 c/mm3, lactic acid 1.99 mmol/L, PCT 0.78 ng/ml, IL6 313 pg/ml and PaFiO2 171.5 mmHg. Conclusion: Spontaneous pneumomediastinum is a frequent complication in patients with COVID-19, being an indicator of poor evolution.(AU)

Relación entre obesidad y enfermedades crónicas no transmisibles e infecciosas / Relationship between obesity and chronic non-communicable and infectious diseases

Introducción: la obesidad aumenta el riesgo a padecer de enfermedades crónicas no transmisibles (ECNT) y afecta el curso de enfermedades de origen infeccioso. Objetivo: examinar la literatura sobre cómo influye la obesidad en la gravedad del cuadro clínico de algunas de las enfermedades no transmisibles y transmisibles de mayor impacto en el Perú. Métodos: investigación documental. Se hace un análisis de contenidos de artículos y documentos de estudios desarrollados en diversos contextos asociados a la presencia de obesidad junto con infecciones o ECNT y en base de datos. Resultados: la condición de obesidad alcanzada por malos hábitos de consumo y baja actividad física, es la principal responsable del elevado índice de las ECNT y por consecuente de las tasas de mortalidad. Conclusiones: el exceso de peso afecta al sistema inmunológico, contribuyendo específicamente en los fenómenos exacerbados de respuesta inflamatoria sistémica, determinada por el aumento de secreción de adipocitoquinas, que predispone al organismo a desarrollar y contraer ECNT y enfermedades infecciosas. (AU)

Introduction: Obesity increases the risk of chronic non-communicable diseases (NCDs) and affects the course of diseases of infectious origin. Objective: Reviewing the literature on how obesity influences the severity of the clinical picture of some of the non-communicable and communicable diseases of greatest impact in Peru. Methods:Documentary research, from studies developed in various contexts associated with the presence of obesity along with infections or NCDs. Results: The condition of obesity reached by bad consumption habits and low physical activity is the main responsible for the high rate of NCDs, consequently, mortality. Conclusions: Excess weight affects the immune system, contributing specifically to exacerbated phenomena of a systemic inflammatory response, determined by increased secretion of adipocytokines, which predisposes the body to develop and contract NCDs and infectious diseases. (AU)

Vertebral fractures are increased in rheumatoid arthritis despite recent therapeutic advances: a case-control study.

Prevalence and risk factors of vertebral fractures in postmenopausal RA women were assessed in 323 patients and compared with 660 age-matched women. Of patients, 24.15% had at least one vertebral fracture vs.16.06% of controls. Age, glucocorticoids and falls were the main fracture risks. Vertebral fractures were associated with disease severity. INTRODUCTION: There is little quality data on the updated prevalence of fractures in rheumatoid arthritis (RA) that may have changed due to advances in the therapeutic strategy in recent years. This study was aimed at analysing the prevalence and risk factors of vertebral fractures in postmenopausal women with RA and comparing it with that of the general population. METHODS: We included 323 postmenopausal women diagnosed with RA from 19 Spanish Rheumatology Departments, randomly selected and recruited in 2018. Lateral radiographs of the thoracic and lumbar spine were obtained to evaluate morphometric vertebral fractures and the spinal deformity index. We analysed subject characteristics, factors related to RA, and fracture risk factors. The control group consisted of 660 age-matched Spanish postmenopausal women from the population-based Camargo cohort. RESULTS: Seventy-eight (24.15%) RA patients had at least one vertebral fracture. RA patients had increased fracture risk compared with controls (106 of 660, 16.06%) (p = 0.02). Logistic regression analysis showed that age (OR 2.17; 95% CI 1.27-4.00), glucocorticoids (OR 3.83; 95% CI 1.32-14.09) and falls (OR 3.57; 95% CI 1.91-6.86) were the independent predictors of vertebral fractures in RA patients. The subgroup with vertebral fractures had higher disease activity (DAS28: 3.15 vs. 2.78, p = 0.038) and disability (HAQ: 0.96 vs. 0.63, p = 0.049), as compared with those without vertebral fractures. CONCLUSION: The risk of vertebral fracture in RA is still high in recent years, when compared with the general population. The key determinants of fracture risk are age, glucocorticoids and falls. Patients with vertebral fractures have a more severe RA.

Management of Psoriasis During Preconception, Pregnancy, Postpartum, and Breastfeeding: A Consensus Statement. / Consenso sobre las actuaciones a seguir durante la edad fértil, el embarazo, el posparto y la lactancia en pacientes con psoriasis.

OBJECTIVE: To develop evidence- and experience-based recommendations for the management of psoriasis during preconception, pregnancy, postpartum, and breastfeeding. METHODS: The nominal group technique and the Delphi method were used. Fifteen experts (12 dermatologists, 2 of whom were appointed coordinators; 1 rheumatologist; and 2 gynecologists) were selected to form an expert panel. Following a systematic review of the literature on fertility, pregnancy, postpartum, and breastfeeding in women with psoriasis, the coordinators drew up a series of preliminary recommendations for discussion by the panel at a nominal group meeting. The experts defined the scope, sections, and intended users of the statement and prepared a final list of recommendations. Consensus was obtained using a Delphi process in which an additional 51 dermatologists rated their level of agreement with each recommendation on a scale of 1 (total disagreement) to 10 (total agreement). Consensus was defined by a score of 7 or higher assigned by at least 70% of participants. Level of evidence and strength of recommendation were reported using the Oxford Center for Evidence-Based Medicine categories. The final statement was approved by the expert panel. RESULTS: The resulting consensus statement includes 23 recommendations on preconception (fertility and contraception), pregnancy (planning, pharmacological management, and follow-up), and breastfeeding (management and follow-up). Consensus was achieved for all recommendations generated except one. CONCLUSIONS: These recommendations for the better management of psoriasis in women of childbearing age could improve outcomes and prognosis.

SCRT1 is a novel beta cell transcription factor with insulin regulatory properties.

Here we show that scratch family transcriptional repressor 1 (SCRT1), a zinc finger transcriptional regulator, is a novel regulator of beta cell function. SCRT1 was found to be expressed in beta cells in rodent and human islets. In human islets, expression of SCRT1 correlated with insulin secretion capacity and the expression of the insulin (INS) gene. Furthermore, SCRT1 mRNA expression was lower in beta cells from T2D patients. siRNA-mediated Scrt1 silencing in INS-1832/13 cells, mouse- and human islets resulted in impaired glucose-stimulated insulin secretion and decreased expression of the insulin gene. This is most likely due to binding of SCRT1 to E-boxes of the Ins1 gene as shown with ChIP. Scrt1 silencing also reduced the expression of several key beta cell transcription factors. Moreover, Scrt1 mRNA expression was reduced by glucose and SCRT1 protein was found to translocate between the nucleus and the cytosol in a glucose-dependent fashion in INS-1832/13 cells as well as in a rodent model of T2D. SCRT1 was also regulated by a GSK3ß-dependent SCRT1-serine phosphorylation. Taken together, SCRT1 is a novel beta cell transcription factor that regulates insulin secretion and is affected in T2D.

The chaperonin CCT controls T cell receptor-driven 3D configuration of centrioles.

T lymphocyte activation requires the formation of immune synapses (IS) with antigen-presenting cells. The dynamics of membrane receptors, signaling scaffolds, microfilaments, and microtubules at the IS determine the potency of T cell activation and subsequent immune response. Here, we show that the cytosolic chaperonin CCT (chaperonin-containing TCP1) controls the changes in reciprocal orientation of the centrioles and polarization of the tubulin dynamics induced by T cell receptor in T lymphocytes forming an IS. CCT also controls the mitochondrial ultrastructure and the metabolic status of T cells, regulating the de novo synthesis of tubulin as well as posttranslational modifications (poly-glutamylation, acetylation, Δ1 and Δ2) of αß-tubulin heterodimers, fine-tuning tubulin dynamics. These changes ultimately determine the function and organization of the centrioles, as shown by three-dimensional reconstruction of resting and stimulated primary T cells using cryo-soft x-ray tomography. Through this mechanism, CCT governs T cell activation and polarity.

Ghrelin suppresses insulin secretion in human islets and type 2 diabetes patients have diminished islet ghrelin cell number and lower plasma ghrelin levels.

It is not known how ghrelin affects insulin secretion in human islets from patients with type 2 diabetes (T2D) or whether islet ghrelin expression or circulating ghrelin levels are altered in T2D. Here we sought out to identify the effect of ghrelin on insulin secretion in human islets and the impact of T2D on circulating ghrelin levels and on islet ghrelin cells. The effect of ghrelin on insulin secretion was assessed in human T2D and non-T2D islets. Ghrelin expression was assessed with RNA-sequencing (n = 191) and immunohistochemistry (n = 21). Plasma ghrelin was measured with ELISA in 40 T2D and 40 non-T2D subjects. Ghrelin exerted a glucose-dependent insulin-suppressing effect in islets from both T2D and non-T2D donors. Compared with non-T2D donors, T2D donors had reduced ghrelin mRNA expression and 75% less islet ghrelin cells, and ghrelin mRNA expression correlated negatively with HbA1c. T2D subjects had 25% lower fasting plasma ghrelin levels than matched controls. Thus, ghrelin has direct insulin-suppressing effects in human islets and T2D patients have lower fasting ghrelin levels, likely as a result of reduced number of islet ghrelin cells. These findings support inhibition of ghrelin signaling as a potential therapeutic avenue for stimulation of insulin secretion in T2D patients.

Intracellular calcium mishandling leads to cardiac dysfunction and ventricular arrhythmias in a mouse model of propionic acidemia.

Propionic acidemia (PA) is a rare metabolic disease associated with mutations in genes encoding the α and ß subunits of the enzyme propionyl-CoA carboxylase. The accumulation of toxic metabolites results in mitochondrial dysfunction, increased reactive oxygen species production and oxidative damage, which have been associated with the disease pathophysiology. Clinical symptoms are heterogeneous and include cardiac complications, mainly cardiac dysfunction and arrhythmias, which are recognized as one of the major life-threatening manifestations in patients. We aimed to investigate the molecular mechanisms underlying the cardiac phenotype using a hypomorphic mouse model (Pcca-/-(A138T)) that recapitulates some biochemical and clinical characteristics of PA. We demonstrate that Pcca-/-(A138T) mice present with depressed cardiac function along with impaired cell contractility when compared to the wild-type mice. Cardiac dysfunction in Pcca-/-(A138T) mice was associated with lower systolic Ca2+ release ([Ca2+]i transients), impairment in the sarcoplasmic reticulum (SR) Ca2+ load and decreased Ca2+ re-uptake by SR-Ca2+ ATPase (SERCA2a). These functional changes correlated well with the depressed activity of SERCA2a, the elevated ROS levels and SERCA2a oxidation rate in cardiomyocytes isolated from Pcca-/-(A138T) mice. In addition, decreased SR-Ca2+ load in Pcca-/-(A138T) cardiomyocytes was associated with increased diastolic Ca2+ release. The increase in Ca2+ sparks, Ca2+ waves and spontaneous [Ca2+]i transients in Pcca-/-(A138T) cardiomyocytes could be responsible for the induction of ventricular arrhythmias detected in these mice. Overall, our results uncover the role of impaired Ca2+ handling in arrhythmias and cardiac dysfunction in PA, and identify new targets for the development of therapeutic approaches for this devastating metabolic disease.

Photoluminescence spectrum using DFT for double-walled carbon nanotubes with metallic constituents.

A theoretical study of the photoluminescence (PL) of double-walled carbon nanotubes (DWCNTs) using density functional theory (DFT) theory is reported in this work. The DWCNTs are of the armchair/armchair type and the structures studied have the arrangements (3,3)/(2,2), (8,8)/(4,4), (12,12)/(6,6), (16,16)/(8,8), (6,6)/(3,3), (10,10)/(5,5), (14,14)/(7,7), and (18,18)/(9,9). The PL spectra were obtained taking into account different DWCNT axial lengths ranging from 0.49 nm ≤ L ≤ 2.33 nm and their inner nanotube diameters in the range of 0.31 ≤ Dinn ≤ 1.22 nm; variations in their inter-wall separations were also considered, 0.18 ≤ Dinw ≤ 0.61 nm. Although the DWCNTs have metallic SWCNT constituents, such structures give rise to photoluminescence due mainly to both curvature effects and inter-wall interaction of the inner and outer nanotubes; these two factors modify significantly their electronic structure; besides, they also lead to these structures to exhibit the quenching effect. We realized calculations at a DFT level in which we used the generalized gradient approximation (GGA) to establish the molecular geometries and the fundamental state energies. To obtain the results of the PL spectra, the constituent SWCNTs were optimized in their ground state, with the hybrid function CAM-B3LYP, which is a mixed functional exchange and correlation, and the base set that was used is the 6-31G.