Reduced circulating levels of sTWEAK are associated with NAFLD and may affect hepatocyte triglyceride accumulation.

CONTEXT: Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome and is strongly associated with obesity, dyslipidaemia and altered glucose regulation. Previous data demonstrated that low circulating levels of tumour necrosis factor weak inducer of apoptosis (sTWEAK) were associated with obesity, diabetes and insulin resistance, all traits associated with an increased risk of NALFD. Circulating sTWEAK levels are expected to be reduced in the presence of NAFLD. OBJECTIVE: We aimed to explore the relationship between NAFLD and circulating sTWEAK levels in obese patients, and to evaluate the effect of sTWEAK on hepatocyte triglyceride accumulation.Design setting and patients:This is an observational case-control study performed in n=112 severely obese patients evaluated for NAFLD by abdominal ultrasound and n=32 non-obese patients without steatosis. Serum sTWEAK concentrations were measured by ELISA. Multivariable analyses were performed to determine the independent predictors of NAFLD. We analysed TWEAK and Fn14 protein expression in liver biopsies by western blotting and immunohistochemistry. An immortalized primary human hepatocyte cell line (HHL) was used to evaluate the effect of sTWEAK on triglyceride accumulation. RESULTS: We observed a reduction in serum circulating sTWEAK concentrations with the presence of liver steatosis. On multivariable analysis, lower sTWEAK concentrations were independently associated with the presence of NAFLD (odds ratio (OR)=0.023; 95% confidence interval: 0.001-0.579; P<0.022). In human hepatocytes, sTWEAK administration reduced fat accumulation as demonstrated by the reduction in palmitic acid-induced accumulation of triglyceride and the decreased expression of cluster of differentiation 36 (CD36) and perilipin 1 and 2 (PLIN1 and PLIN2) genes. CONCLUSIONS: Decreased sTWEAK concentrations are independently associated with the presence of NAFLD. This is concordant with the observation that TWEAK reduces lipid accumulation in human liver cells.

Burnout syndrome in internal medicine specialists and factors associated with its onset. / Síndrome de burnout en especialistas de medicina interna y factores asociados a su desarrollo.

BACKGROUND AND OBJECTIVES: Burnout is a psychosocial syndrome caused by stressful working conditions and affects 30-60% of medical personnel. The aim of this study was to assess the burnout rate of Spanish internists and the factors related to its onset. MATERIAL AND METHODS: We conducted a survey of work conditions followed by the Maslach Burnout Inventory, which was disseminated through the email registry and social networks of the Spanish Society of Internal Medicine. We performed a descriptive study and a univariate and multivariate analysis assessing the variables associated with burnout syndrome. RESULTS: A total of 934 internists (58.8% women and a median age of 40.0 years) answered the survey. Some 55.0% of the internists indicated high emotional fatigue, 61.7% indicated a high sense of depersonalisation, and 58.6% indicated low personal fulfilment. Some 33.4% of the interns experienced burnout. Burnout syndrome was independently related to age (OR 0.96; 95% CI 0.94-0.98), poor work environment (OR 1.94; 95% CI 1.31-2.82), insufficient wages (OR 1.79; 95% CI 1.20-2.67), receiving threats (OR 1.703; 95% CI 1.204-2.410) and the feeling of a lack of professional progress (OR 2.83; 95% CI 1.92-4.17). CONCLUSIONS: Burnout syndrome affects 33.4% of internists in Spain, and its onset is independently related with age, poor work environment, a lack of professional progress, insufficient financial remuneration and experiencing threats by patients or colleagues.

Plasma visfatin concentrations increase in both hyper and hypothyroid subjects after normalization of thyroid function and are not related to insulin resistance, anthropometric or inflammatory parameters.

OBJECTIVE: The objective of this study was to evaluate plasma visfatin levels in thyroid dysfunction and its relationship with inflammatory, anthropometric and insulin resistance parameters. DESIGN AND PATIENTS: Twenty-four hyperthyroid and 27 hypothyroid patients were studied before and after treatment. Forty-five euthyroid subjects were used as control group. MEASUREMENTS: Fasting plasma visfatin, IL-6, C reactive protein, adiponectin, thyroid hormones, waist-to-hip ratio, BMI, percentage of body fat and homeostasis model insulin resistance index (HOMA-IR) were measured. RESULTS: Hyperthyroid patients showed increased insulin resistance, IL-6 and visfatin levels compared with controls (3.21 +/- 3.0 vs. 1.67 +/- 0.75, P = 0.022; 3.35 +/- 0.41 vs. 2.10 +/- 0.25 pg/ml, P = 0.016; and 37.4 +/- 5.81 vs. 23.79 +/- 4.2 ng/ml, P = 0.061 respectively). After normalization of thyroid function, IL-6 levels and HOMA-IR decreased (2.35 +/- 0.37 vs. 2.10 +/- 0.25 pg/ml, P = 0.045 and 3.21 +/- 0.60 vs. 2.28 +/- 0.38, P = 0.032 respectively), while body weight, adiposity and visfatin levels increased (26.1 +/- 1.2 vs. 26.7 +/- 1.2 kg/m(2), P = 0.049; 30.9 +/- 1.6 vs. 32.2 +/- 1.6%, P = 0.007; and 37.4 +/- 5.81 vs. 63.13 +/- 8.72 ng/ml, P = 0.047 respectively). C reactive protein and adiponectin levels were similar to those of the control group. Hypothyroid patients showed high visfatin levels (40.59 +/- 3.07 vs. 29.34 +/- 4.9 ng/ml, P = 0.049) that increased after treatment (81.4 +/- 9.2 ng/ml, P = 0.001) without changes in anthropometric or insulin resistance parameters. C reactive protein, IL-6 and adiponectin levels were similar to those of the control group. No correlations between visfatin and any analysed parameter were found in either hyper- or hypothyroidism. CONCLUSION: Visfatin exhibits a marked increase after normalization of thyroid function in both hyper and hypothyroid patients. We suggest that visfatin may play a role in the hormone stabilization process independent of anthropometric, inflammatory or insulin resistance variables.

Getting to know internal medicine mentors: new training requirements. / Conociendo a los tutores de Medicina Interna: nuevas necesidades para la formación.

INTRODUCTION AND OBJECTIVES: Mentors are responsible for planning the residents' learning. The aim of this study was to determine the situation of internal medicine mentors in Spain and detect areas of improvement that can facilitate their work. MATERIAL AND METHODS: Online surveys were sent to internal medicine mentors from May to July 2017, the results of which were subsequently analysed. RESULTS: A total of 110 mentors from 13 autonomous communities and from hospitals of all levels with courses in internal medicine responded to the survey. Of these mentors, 63 were men (57.3%), and the mean age was 48 years. The mean experience as mentors was 8.5 years. Some 88.2% of the cases had a ratio of 5 residents to 1 mentor; 46% of the mentors believed this ratio should be decreased to optimize their work. A third of the mentors were chosen by the heads of the department, and 30% had not previously taken courses on training. The mentor-resident interview was used by most mentors (96.4%) as a communication tool. A quarter of the rotations were not planned by the mentors, and only half had contact with the centres where the residents performed the external rotations. Sixty-one percent of the mentors were of the opinion that resident assessments were not conducted properly, with very little use of the new assessment tools. CONCLUSIONS: Reducing the mentor-resident ratio and adding training in assessment techniques and learning development could improve the quality of the mentoring.

Fifth-year internal medicine residents in Spain: A survey on education, assessment of competencies and job perspectives. / Residentes de medicina interna de quinto año en España: encuesta sobre educación, evaluación de competencias y perspectivas de empleo.

BACKGROUND: Specialist training is based on the gradual acquisition of expertise, skills and responsibilities. The aim of this study is to determine the opinion of residents regarding their training. MATERIAL AND METHODS: This was a cross-sectional descriptive study based on an online survey of 5th-year residents during February and March 2017. RESULTS: A total of 194 residents (62.8% of the total) responded to the survey, 62.9% of whom were women and 50% of whom were younger than 30years, representing hospitals from all levels and from the 17 autonomous communities. More than 80% of the residents choose the specialty once again and believed that the duration of the residence was appropriate; however, 76.3% would eliminate some of their rotations. Most of the residents did not know the objectives of each rotation, and 37.1% felt they were not adequately supervised. Some 82.5% would change the evaluation system, and 68.0% would favour performing an excellence test. Most of the residents had published at least one article or performed one presentation at a congress; however, only 27.8% had completed a doctoral thesis. Although 74.7% of the internists believed they would find employment, only 28.4% had an offer 1month after completing their residence. CONCLUSIONS: The residents are satisfied with their training, although there is still a deficit in supervision and dissatisfaction with the method of assessing their knowledge and the precarious job market during the first year for specialists.

Haematopoiesis radioprotection in Balb/c mice by an aqueous mycelium extract from the Basidiomycete Pleurotus ostreatus mushroom.

The study examined the radioprotective activity of an aqueous extract from Pleurotus ostreatus mycelium administered to Balb/c mice. Male mice were whole-body irradiated on day 0 ((60)Co, at 0.43 Gy/min) and divided into two groups. The extract was administered intraperitoneally to one group (100 mg/kg) on days - 10 to - 6 and - 2 to +1 with respect to the irradiation. The irradiated-control group was injected with saline solution; non-irradiated mice were used as negative controls. The radioprotective effect was evident by increases in bone marrow cellularity (5.1 × 10(6)/femur vs. 1.1 × 10(6)/femur in saline-control mice, p < 0.05), leucocyte counts (10.5 × 10(9)/L vs. 4.5 × 10(9)/L, p < 0.05), and spleen cellularity (11.2 × 10(7)/spleen vs. 6.2 × 10(7)/spleen, p < 0.05). The extract stimulated macrophage phagocytic activity as judged by a faster rate of carbon clearance in terms of absorbance ratios (1.62 vs. 2.01, p < 0.05). Therefore, this extract may be a candidate therapeutic agent with radioprotective activity for haematopoiesis damage, particularly to cells involved in immune function.

Trigeminal nucleus caudalis dorsal root entry zone radiofrequency thermocoagulation for invalidating facial pain.

INTRODUCTION: Facial pain syndromes occasionally result in desperate clinical settings completely unresponsive to any known therapy. Trigeminal nucleus caudalis dorsal root entry zone (DREZ) lesion is reported to be of benefit in such cases. In 1982 Nashold performed the first DREZ caudalis lesion in a patient with anaesthesia dolorosa. PATIENTS AND METHODS: From 1994 to 2002 we have performed six DREZ caudalis lesions on five patients with extremely invalidating facial pain resistant to multiple pharmacological and surgical therapies. Pain was secondary to previous craniofacial surgery in all but one case. Pain presented as anaesthesia dolorosa or atypical facial pain so severe as to interfere with personal hygiene and even to prevent patients from oral feeding. A midline suboccipital approach was used and radiofrequency lesions (at the trigeminal nucleus caudalis in the cervicomedullary junction) were made at 1-mm intervals, 75 (o)C for 15 seconds each along the ipsilateral posterolateral sulcus from the cervical DREZ up to the obex. RESULTS: Pain relief was complete and permanent in two patients. Three patients experienced significant improvement but pain recurred in two (weeks to a few months after the procedure). No patient's pain was made worse. A patient with persistent postoperative nasolabial pain was re-operated on (improving again but ultimately remaining unchanged). Air venous embolism related to the sitting position (3 patients) during surgery and bradycardia due to manipulation in medulla (2 patients) occurred during some of the procedures without any cardiovascular or neurological repercussion. Postoperative complications included mild and transient ataxia and monoparesia (3 patients). DISCUSSION: Facial pain secondary to craniofacial surgery is known to be among the least responsive to treatment and a true challenge for pain clinicians. Actual indications for this procedure, operative technical details and the results of our series compared to previous reports are reviewed. CONCLUSION: Trigeminal nucleus caudalis radiofrequency thermocoagulation is an effective neurosurgical procedure for the treatment of chronically debilitating and desperate facial pain syndromes with acceptable morbidity.

[Surgery unit for epilepsy]. / La Unidad de Cirugía de la Epilepsia.

INTRODUCTION: Only few medically refractory epileptic patients are evaluated for surgical treatment, in spite of the good results obtained at the Centers where epilepsy surgery is performed. OBJECTIVE: We are presenting the way the Gregorio Marañón Hospital Epilepsy Surgery Unit functions and their casuistry. PATIENTS AND METHODS: This Unit is composed by members of the Services of Neurosurgery, Neurology, Neurophysiology, Neuroradiology, Psychology, Neuropediatry, Nuclear Medicine and Neuroanestesiology. Patients are studied by means of protocols. RESULTS: Twenty cases were operated upon. The procedures were temporal lobectomy in 9 cases, amygdalo-hipocampectomy in 4, frontal lobectomy in 3, frontal topectomy in 2, partial hemispherectomy in 1 and vagal nerve stimulation in 1. In 16 of the 19 surgery specimen there were some pathological abnormalities. In the short follow-up 13 patients are seizures free experience significant improvement.

Impaired endothelial function is not associated with arterial stiffness in adults with type 1 diabetes.

AIM: This study investigated the relationship between endothelial dysfunction (ED) and arterial stiffness (AS) in adults with type 1 diabetes and no clinical cardiovascular (CV) disease. METHODS: A total of 68 patients with type 1 diabetes and 68 age- and gender-matched healthy (non-diabetic) subjects were evaluated. ED was assessed by reactive hyperaemia peripheral arterial tonometry (RH-PAT) and by serum concentrations of soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1) and E-selectin. AS was assessed by aortic pulse wave velocity (aPWV). All statistical analyses were stratified by gender. RESULTS: Adults with type 1 diabetes had RH-PAT index scores similar to those of their matching controls [men: 1.55 (1.38-1.98)% versus 1.61 (1.40-2.17)%, P=0.556; women: 2.07 (1.55-2.31)% versus 2.08 (1.79-2.49)%; P=0.215]. However, after adjusting for potential confounders, type 1 diabetes emerged as the main determinant of the RH-PAT index in women. Also, differences between genders in both the controls and type 1 diabetes patients disappeared. Men with diabetes had higher serum concentrations of E-selectin, and women had higher serum concentrations of sICAM-1, sVCAM-1 and E-selectin than their respective controls. However, after adjusting for potential confounders, only the differences in sICAM-1 (women) and E-selectin (both genders) remained significant. No association was found between aPWV and the RH-PAT index and ED markers after adjusting for CV risk factors. CONCLUSION: ED was increased in adults with type 1 diabetes compared with age-matched non-diabetic subjects. Also, gender differences in ED were lost in type 1 diabetes. However, ED was not associated with AS after adjusting for potential confounders. These findings suggest that ED occurs earlier than AS in type 1 diabetes.

Insulin resistance, low-grade inflammation and type 1 diabetes mellitus.

To assess the relationships between insulin resistance and low-grade inflammation in subjects with type 1 diabetes mellitus (T1DM) who do not have clinical macrovascular complications. A total of 120 subjects diagnosed with T1DM 14 years before were evaluated for the following: (1) sex, age, body mass index, waist-to-hip ratio (WHR), blood pressure, smoking, alcohol intake, insulin dose, HbA1c and lipid profile; (2) microvascular complications; (3) plasma concentrations of soluble fractions of tumour necrosis factor-α receptors type 1 and 2, interleukin-6, adiponectin, leptin and high-sensitivity C-reactive protein (hs-CRP); and (4) insulin resistance (estimation of the glucose disposal rate-eGDR). Those subjects with an eGDR below the median of the same sex group were classified as insulin resistant and the others as insulin sensitive. Insulin-resistant men, compared to the insulin-sensitive, had higher WHR (0.89 ± 0.08 vs. 0.83 ± 0.05; P < 0.01), higher systolic [121 (118-125) vs. 114 (108-120) mmHg; P = 0.01] and diastolic [73 (66-80) vs. 67 (70-73) mmHg; P = 0.02] blood pressures, higher HbA1c values [8.7 (8.1-9.9) vs. 7.5 (7.2-8.0) %; P < 0.01] and higher hs-CRP concentrations [1.16 (0.61-3.20) vs. 0.49 (0.31-0.82) mg/dl; P = 0.01], but no other significant differences between groups were found. Insulin-resistant women had higher WHR and HbA1c values, compared to the insulin-sensitive, but they did not have any other differences. In men, hs-CRP correlated significantly with WHR and HbA1c (r = 0.363; P = 0.016 and r = 0.317; P = 0.036, respectively), after adjusting for age, alcohol intake, smoking and microvascular complications. Insulin-resistant men with T1DM have an increase in plasma concentrations of hs-CRP. Central obesity and HbA1c are its main determinants.