Time Series Transcriptomic Analysis of Bronchoalveolar Lavage Cells from Piglets Infected with Virulent or Low-Virulent Porcine Reproductive and Respiratory Syndrome Virus 1.

Porcine reproductive and respiratory syndrome virus (PRRSV) has evolved to escape the immune surveillance for a survival advantage leading to a strong modulation of host's immune responses and favoring secondary bacterial infections. However, limited data are available on how the immunological and transcriptional responses elicited by virulent and low-virulent PRRSV-1 strains are comparable and how they are conserved during the infection. To explore the kinetic transcriptional signature associated with the modulation of host immune response at lung level, a time-series transcriptomic analysis was performed in bronchoalveolar lavage cells upon experimental in vivo infection with two PRRSV-1 strains of different virulence, virulent subtype 3 Lena strain or the low-virulent subtype 1 3249 strain. The time-series analysis revealed overlapping patterns of dysregulated genes enriched in T-cell signaling pathways among both virulent and low-virulent strains, highlighting an upregulation of co-stimulatory and co-inhibitory immune checkpoints that were disclosed as Hub genes. On the other hand, virulent Lena infection induced an early and more marked "negative regulation of immune system process" with an overexpression of co-inhibitory receptors genes related to T-cell and NK cell functions, in association with more severe lung lesion, lung viral load, and BAL cell kinetics. These results underline a complex network of molecular mechanisms governing PRRSV-1 immunopathogenesis at lung level, revealing a pivotal role of co-inhibitory and co-stimulatory immune checkpoints in the pulmonary disease, which may have an impact on T-cell activation and related pathways. These immune checkpoints, together with the regulation of cytokine-signaling pathways, modulated in a virulence-dependent fashion, orchestrate an interplay among pro- and anti-inflammatory responses. IMPORTANCE Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the major threats to swine health and global production, causing substantial economic losses. We explore the mechanisms involved in the modulation of host immune response at lung level performing a time-series transcriptomic analysis upon experimental infection with two PRRSV-1 strains of different virulence. A complex network of molecular mechanisms was revealed to control the immunopathogenesis of PRRSV-1 infection, highlighting an interplay among pro- and anti-inflammatory responses as a potential mechanism to restrict inflammation-induced lung injury. Moreover, a pivotal role of co-inhibitory and co-stimulatory immune checkpoints was evidenced, which may lead to progressive dysfunction of T cells, impairing viral clearance and leading to persistent infection, favoring as well secondary bacterial infections or viral rebound. However, further studies should be conducted to evaluate the functional role of immune checkpoints in advanced stages of PRRSV infection and explore a possible T-cell exhaustion state.

Laparoscopic and robotic intracorporeal resection and end-to-end anastomosis in left colectomy: a prospective cohort study - stage 2a IDEAL framework for evaluating surgical innovation.

PURPOSE: To analyze the safety and feasibility of intracorporeal resection and anastomosis in upper rectum, sigmoid, and left colon surgery, via both laparoscopic and robotic approaches. The secondary aim was to assess possible short-term differences between laparoscopic versus robotic surgery. METHODS: A prospective observational cohort study according to IDEAL framework exploration and assessment stage (Development, stage 2a), evaluating and comparing the laparoscopic approach and the robotic approach in left colon, sigmoid, and upper rectum surgery with intracorporeal resection and end-to-end anastomosis. Demographic, preoperative, surgical, and postoperative variables of patients undergoing laparoscopic and robotic surgery are described and compared according to the surgical technique used. RESULTS: Between May 2020 and March 2022, seventy-nine patients were consecutively included in the study, 41 operated via laparoscopy (laparoscopic left colectomy: LLC) and 38 by robotic surgery (robotic left colectomy: RLC). There were no statistically significant differences between the two groups in terms of demographic variables. In surgical variables, the median surgical times differed significantly: 198 min (SD 48 min) for LLC vs. 246 min (SD 72 min) for RLC (p = 0.01, 95% CI: - 75.2 to - 20.5)). The only significant difference regarding postoperative complications was a higher degree of relevant morbidity in the LLC (Clavien-Dindo > II (14.6% vs. 0%, p = 0.03) and Comprehensive Complication Index (IQR 22 vs. IQR 0, p = 0.03). The pathological results were similar in both approaches. CONCLUSION: Laparoscopic and robotic intracorporeal resection and anastomosis are feasible and safe, and obtain similar surgical, postoperative, and pathological results than described in literature. However, morbidity seems to be higher in LLC group with fewer relevant postoperative complications. The results of this study enable us to proceed to stage 2b of the IDEAL framework. CLINICAL TRIAL REGISTRATIONS: The study is registered in Clinical trials with the registration code NCT0445693.

Primary Cutaneous Lymphoma Registry of the Spanish Academy of Dermatology and Venereology (AEDV): Data for the First 5 Years. / Registro de linfomas cutáneos primarios (RELCP) de la AEDV: datos tras 5 años de funcionamiento.

BACKGROUND AND OBJECTIVE: Primary cutaneous lymphomas (PCL) are uncommon. Observations based on the first year of data from the Spanish Registry of Primary Cutaneous Lymphomas (RELCP, in its Spanish abbreviation) of the Spanish Academy of Dermatology and Venereology (AEDV) were published in February 2018. This report covers RELCP data for the first 5 years. PATIENTS AND METHODS: RELCP data were collected prospectively and included diagnosis, treatments, tests, and the current status of patients. We compiled descriptive statistics of the data registered during the first 5 years. RESULTS: Information on 2020 patients treated at 33 Spanish hospitals had been included in the RELCP by December 2021. Fifty-nine percent of the patients were men; the mean age was 62.2 years. The lymphomas were grouped into 4 large diagnostic categories: mycosis fungoides/Sézary syndrome, 1112 patients (55%); primary B-cell cutaneous lymphoma, 547 patients (27.1%); primary CD30+lymphoproliferative disorders, 222 patients (11%), and other T-cell lymphomas, 116 patients (5.8%). Nearly 75% of the tumors were registered in stage I. After treatment, 43.5% achieved complete remission and 27% were stable at the time of writing. Treatments prescribed were topical corticosteroids (1369 [67.8%]), phototherapy (890 patients [44.1%]), surgery (412 patients [20.4%]), and radiotherapy (384 patients [19%]). CONCLUSION: The characteristics of cutaneous lymphomas in Spain are similar to those reported for other series. The large size of the RELCP registry at 5 years has allowed us to give more precise descriptive statistics than in the first year. This registry facilitates the clinical research of the AEDV's lymphoma interest group, which has already published articles based on the RELCP data.

Long-term outcome predictors after functional remediation in patients with bipolar disorder.

BACKGROUND: Improving functioning in patients with bipolar disorder (BD) is one of the main objectives in clinical practice. Of the few psychosocial interventions that have been specifically developed to enhance the psychosocial outcome in BD, functional remediation (FR) is one which has demonstrated efficacy. The aim of this study was to examine which variables could predict improved functional outcome following the FR intervention in a sample of euthymic or subsyndromal patients with BD. METHODS: A total of 92 euthymic outpatients were included in this longitudinal study, with 62 completers. Partial correlations controlling for the functional outcome at baseline were calculated between demographic, clinical and neurocognitive variables, and functional outcome at endpoint was assessed by means of the Functioning Assessment Short Test scale. Next, a multiple regression analysis was run in order to identify potential predictors of functional outcome at 2-year follow-up, using the variables found to be statistically significant in the correlation analysis and other variables related to functioning as identified in the previous scientific literature. RESULTS: The regression model revealed that only two independent variables significantly contributed to the model (F(6,53): 4.003; p = 0.002), namely verbal memory and inhibitory control. The model accounted for 31.2% of the variance. No other demographic or clinical variable contributed to the model. CONCLUSIONS: Results suggest that patients with better cognitive performance at baseline, especially in terms of verbal memory and executive functions, may present better functional outcomes at long term follow-up after receiving functional remediation.

Uninformative and unuseful: why it is necessary to actively challenge COVID-19 antibody testing postvaccination.

OBJECTIVES: We aimed to assess the evidence on the usefulness of postvaccination testing of COVID-19 antibodies. STUDY DESIGN: We used a descriptive analytical approach. METHODS: We synthesized insights of studies on the immunological responses to SARS-CoV-2 after natural infection or vaccination and recommendations by regulatory institutions, such as the Food and Drug Administration and the Centers for Disease Control and Prevention in the United States. RESULTS: Based on the multiple humoral and cellular responses elicited by either the virus or the vaccines, the high variability of antibodies in blood, and the lack of correlation between the presence of antibodies and active cellular immunity against SARS-CoV-2, there has been explicit advice against assessing immunological status postvaccination. CONCLUSIONS: Postvaccination antibody testing is not warranted to assess immunity status for COVID-19. Patients may misinterpret results, leading to the spread of misinformation regarding vaccine efficacy or the need to continue self-protection or the protection of others. Therefore, public health authorities should actively challenge the promotion and commercialization of this type of tests.

Characterization and Optimization of the Novel Transient Receptor Potential Melastatin 2 Antagonist tatM2NX.

Transient receptor potential melastatin 2 (TRPM2) is a calcium-permeable channel activated by adenosine diphosphate ribose metabolites and oxidative stress. TRPM2 contributes to neuronal injury in the brain caused by stroke and cardiac arrest among other diseases including pain, inflammation, and cancer. However, the lack of specific inhibitors hinders the study of TRPM2 in brain pathophysiology. Here, we present the design of a novel TRPM2 antagonist, tatM2NX, which prevents ligand binding and TRPM2 activation. We used mutagenesis of tatM2NX to determine the structure-activity relationship and antagonistic mechanism on TRPM2 using whole-cell patch clamp and Calcium imaging in human embryonic kidney 293 cells with stable human TRPM2 expression. We show that tatM2NX inhibits over 90% of TRPM2 channel currents at concentrations as low as 2 µM. Moreover, tatM2NX is a potent antagonist with an IC50 of 396 nM. Our results from tatM2NX mutagenesis indicate that specific residues within the tatM2NX C terminus are required to confer antagonism on TRPM2. Therefore, the peptide tatM2NX represents a new tool for the study of TRPM2 function in cell biology and enhances our understanding of TRPM2 in disease. SIGNIFICANCE STATEMENT: TatM2NX is a potent TRPM2 channel antagonist with the potential for clinical benefit in neurological diseases. This study characterizes interactions of tatM2NX with TRPM2 and the mechanism of action using structure-activity analysis.

Three-year longitudinal cognitive functioning in patients recently diagnosed with bipolar disorder.

OBJECTIVE: The longitudinal course of neuropsychological functioning after the first manic episode in bipolar disorder is unknown. The present study evaluated cognitive change in bipolar disorder in the first 3 years after the initial manic episode. METHODS: Ninety-one newly diagnosed patients with bipolar disorder and 61 demographically similar healthy participants received a neuropsychological evaluation assessing multiple cognitive domains at baseline, 1-year, and 3-year time points. Patients also received clinical assessments including mood ratings at all time points. RESULTS: Patients showed deficits in all domains at baseline, but similar longitudinal trajectories across time relative to healthy participants in most cognitive domains. For processing speed, patients showed more gains than controls from baseline to 1 year, but these gains stabilized thereafter. Patients with alcohol/substance abuse showed an initial delay but subsequent recovery in executive functioning. Patients who discontinued antipsychotic treatment showed better cognitive outcomes in verbal memory. CONCLUSION: Appropriately treated patients with bipolar disorder showed favorable cognitive outcome in the first 3 years after experiencing an initial manic episode, arguing against cognitive neuroprogression at this stage of the illness. Discontinuation of antipsychotic treatment may be associated with better cognitive outcomes, but clarification of the role of antipsychotics on cognitive functioning requires further investigation.

Vitamin D deficiency in solid-organ transplant recipients from a Spanish Mediterranean population.

BACKGROUND: Solid-organ transplant recipients (SOTRs) are at risk of developing vitamin D deficiency, mainly caused by reduced sunlight exposure with subsequent low vitamin D synthesis in the skin. AIM: To analyse whether SOTRs from a Spanish Mediterranean region were vitamin D-deficient. METHODS: This was a cross-sectional, descriptive and observational study in a transplantation-specialized Dermatological Unit from a Mediterranean area to determine the calcidiol levels of a cohort of 78 consecutively attending patients not receiving vitamin D supplements. Serum 25(OH)D3 levels were determined and clinical characteristics were collected. Logistic regression analysis was used to analyse variables associated with dichotomized 25(OH)D3 levels (≤ or > 10 ng/mL). RESULTS: The cohort comprised 30 lung, 29 kidney and 19 liver transplant recipients. Mean calcidiol was 18 ± 9 ng/mL. Deficiency of 25(OH)D3 was present in 19% of patients, while 68% had insufficient levels and 13% had sufficient levels. Following multivariate logistic regression analysis, the season of blood sampling remained the only predictor of deficient 25(OH)D3 levels. CONCLUSION: Despite living in a mid-latitude country with sunny weather, our SOTR population was at high risk of developing hypovitaminosis D, especially in autumn/winter. Avoiding sun exposure is important to prevent skin cancer, but careful monitoring of vitamin D status is recommended, with supplementation if hypovitaminosis D is detected.

Assessing and addressing cognitive impairment in bipolar disorder: the International Society for Bipolar Disorders Targeting Cognition Task Force recommendations for clinicians.

OBJECTIVES: Cognition is a new treatment target to aid functional recovery and enhance quality of life for patients with bipolar disorder. The International Society for Bipolar Disorders (ISBD) Targeting Cognition Task Force aimed to develop consensus-based clinical recommendations on whether, when and how to assess and address cognitive impairment. METHODS: The task force, consisting of 19 international experts from nine countries, discussed the challenges and recommendations in a face-to-face meeting, telephone conference call and email exchanges. Consensus-based recommendations were achieved through these exchanges with no need for formal consensus methods. RESULTS: The identified questions were: (I) Should cognitive screening assessments be routinely conducted in clinical settings? (II) What are the most feasible screening tools? (III) What are the implications if cognitive impairment is detected? (IV) What are the treatment perspectives? Key recommendations are that clinicians: (I) formally screen cognition in partially or fully remitted patients whenever possible, (II) use brief, easy-to-administer tools such as the Screen for Cognitive Impairment in Psychiatry and Cognitive Complaints in Bipolar Disorder Rating Assessment, and (III) evaluate the impact of medication and comorbidity, refer patients for comprehensive neuropsychological evaluation when clinically indicated, and encourage patients to build cognitive reserve. Regarding question (IV), there is limited evidence for current evidence-based treatments but intense research efforts are underway to identify new pharmacological and/or psychological cognition treatments. CONCLUSIONS: This task force paper provides the first consensus-based recommendations for clinicians on whether, when, and how to assess and address cognition, which may aid patients' functional recovery and improve their quality of life.

Heterogeneity of functional outcomes in patients with bipolar disorder: a cluster-analytic approach.

OBJECTIVE: The aim was to examine the heterogeneity of psychosocial outcomes in euthymic bipolar disorder (BD) patients and analyse the potential influence of distinct variables on functioning. METHOD: Using a hierarchical cluster exploratory analysis, 143 euthymic patients with diagnosis of BD were grouped according to their functional performance based on domains scores of the Functioning Assessment Short Test (FAST). The resulting groups were compared on sociodemographic, clinical and neurocognitive variables to find factors associated with each functional cluster. RESULTS: Patients were grouped in three functional profiles: patients with good functioning in all the FAST areas, patients with an intermediate profile showing great difficulties in the occupational domain and milder difficulties in most of the rest domains, and a third group with serious difficulties in almost all functional areas. Both functionally impaired groups were characterized by higher subthreshold symptoms (depressive and manic) and higher unemployment rates. The most functionally impaired group also showed lower scores on some measures of processing speed. CONCLUSION: Two of three functional profiles showed some kind of impairment which was associated with subsyndromal symptoms and cognitive performance. These patterns should be taken into consideration to develop more individualized interventions to restore, or improve, psychosocial outcomes.

Effects of topical capsaicin combined with moderate exercise on insulin resistance, body weight and oxidative stress in hypoestrogenic obese rats.

BACKGROUND: Hypoestrogenic (HE) women are one of the most vulnerable groups for the development of obesity and its complications. Capsaicin and exercise have demonstrated to reduce body weight and to improve insulin sensitivity in different animal models, but it is unknown whether their combination could be useful in HE obese females. METHODS: We investigated whether topical capsaicin, exercise or their combination had better therapeutic effects in an obesity-hypoestrogenism model. Ovariectomized Wistar rats were given a 30% sucrose solution (HE-Obese (HEOb)) or purified water (HE) during 28 weeks ad libitum; four experimental groups per each condition. After shaving the abdominal skin, cold cream vehicle was applied to the Sedentary groups (Sed) and capsaicin cream 0.075% (0.6 mg kg-1 per day) to the Capsaicin groups (Cap). Exercise (Ex) groups ran on a treadmill every day for 20 min at speeds from 9 to 18 m per min increased every 10 days; combination groups (Cap+Ex) were given topical capsaicin 90 min before exercise. The treatments were performed for 6 weeks, and caloric intake and body weight were monitored. At the end of the experimental protocol, glucose tolerance tests were performed, the animals were killed by decapitation; blood and organs were obtained to perform oxidative profile, histology, biochemical analyses and Western blot. RESULTS: In HEOb rats, the combined therapy reduced caloric intake, body weight and abdominal fat in a higher proportion than the individual treatments; it also decreased insulin resistance (IR), oxidative stress and pancreatic islet size. It was the only treatment that significantly increased p-AMPK levels in the soleus muscle. In HE rats, topical capsaicin was the only treatment that reduced glucose intolerance and improved the oxidative profile in a higher proportion than the combined therapy or Ex alone. CONCLUSIONS: Capsaicin per se or its combination with moderate exercise could be a useful therapy against complications linked to obesity-IR in HE females.

Methodological recommendations for cognition trials in bipolar disorder by the International Society for Bipolar Disorders Targeting Cognition Task Force.

OBJECTIVES: To aid the development of treatment for cognitive impairment in bipolar disorder, the International Society for Bipolar Disorders (ISBD) convened a task force to create a consensus-based guidance paper for the methodology and design of cognition trials in bipolar disorder. METHODS: The task force was launched in September 2016, consisting of 18 international experts from nine countries. A series of methodological issues were identified based on literature review and expert opinion. The issues were discussed and expanded upon in an initial face-to-face meeting, telephone conference call and email exchanges. Based upon these exchanges, recommendations were achieved. RESULTS: Key methodological challenges are: lack of consensus on how to screen for entry into cognitive treatment trials, define cognitive impairment, track efficacy, assess functional implications, and manage mood symptoms and concomitant medication. Task force recommendations are to: (i) enrich trials with objectively measured cognitively impaired patients; (ii) generally select a broad cognitive composite score as the primary outcome and a functional measure as a key secondary outcome; and (iii) include remitted or partly remitted patients. It is strongly encouraged that trials exclude patients with current substance or alcohol use disorders, neurological disease or unstable medical illness, and keep non-study medications stable. Additional methodological considerations include neuroimaging assessments, targeting of treatments to illness stage and using a multimodal approach. CONCLUSIONS: This ISBD task force guidance paper provides the first consensus-based recommendations for cognition trials in bipolar disorder. Adherence to these recommendations will likely improve the sensitivity in detecting treatment efficacy in future trials and increase comparability between studies.

A simulator for training in endovascular aneurysm repair: The use of three dimensional printers.

OBJECTIVES: To develop an endovascular aneurysm repair (EVAR) simulation system using three dimensional (3D) printed aneurysms, and to evaluate the impact of patient specific training prior to EVAR on the surgical performance of vascular surgery residents in a university hospital in Brazil. METHODS: This was a prospective, controlled, single centre study. During 2015, the aneurysms of patients undergoing elective EVAR at São Paulo University Medical School were 3D printed and used in training sessions with vascular surgery residents. The 3D printers Stratasys-Connex 350, Formlabs-Form1+, and Makerbot were tested. Ten residents were enrolled in the control group (five residents and 30 patients in 2014) or the training group (five residents and 25 patients in 2015). The control group performed the surgery under the supervision of a senior vascular surgeon (routine procedure, without simulator training). The training group practised the surgery in a patient specific simulator prior to the routine procedure. Objective parameters were analysed, and a subjective questionnaire addressing training utility and realism was answered. RESULTS: Patient specific training reduced fluoroscopy time by 30% (mean 48 min, 95% confidence interval [CI] 40-58 vs. 33 min, 95% CI 26-42 [p < .01]), total procedure time by 29% (mean 292 min [95% CI 235-336] vs. 207 [95% CI 173-247]; p < .01), and volume of contrast used by 25% (mean 87 mL [95% CI 73-103] vs. 65 mL [95% CI 52-81]; p = .02). The residents considered the training useful and realistic, and reported that it increased their self confidence. The 3D printers Form1+ (using flexible resin) and Makerbot (using silicone) provided the best performance based on simulator quality and cost. CONCLUSION: An EVAR simulation system using 3D printed aneurysms was feasible. The best results were obtained with the 3D printers Form1+ (using flexible resin) and Makerbot (using silicone). Patient specific training prior to EVAR at a university hospital in Brazil improved residents' surgical performance (based on fluoroscopy time, surgery time, and volume of contrast used) and increased their self confidence.

Lower cognitive functioning as a predictor of weight gain in bipolar disorder: a 12-month study.

OBJECTIVE: In cross-sectional studies, elevated body mass index (BMI) is associated with cognitive impairment in bipolar disorder (BD). We investigated the direction of this association by prospectively examining changes in BMI and cognition. METHOD: We measured BMI and performance in six cognitive domains over 12 months in 80 adolescent and young adult BD patients and 46 healthy comparison subjects (HS). Ninety-three percent of patients received pharmacotherapy and 84% were euthymic. We used repeated-measures ancova and longitudinal mixed models to investigate whether (i) higher BMI and increasing BMI over time predicted lower subsequent cognitive functioning, and (ii) lower cognitive functioning and changes in cognition predicted increasing BMI. RESULTS: Neither baseline BMI nor BMI change predicted lower cognitive functioning. Lower baseline scores in attention, verbal memory, working memory, and a composite measure of global cognition predicted increasing BMI in patients and HS. In patients, lower cognitive functioning remained associated with increasing BMI when clinical and treatment variables were adjusted for. Improvement in working memory predicted a smaller subsequent BMI increase in patients. CONCLUSION: Lower cognitive functioning in specific domains predicts increasing BMI in patients with BD and healthy young adults. Targeting cognition may be important for minimizing weight gain in BD.

3D quantitative assessment of response to fractionated stereotactic radiotherapy and single-session stereotactic radiosurgery of vestibular schwannoma.

OBJECTIVES: To determine clinical outcome of patients with vestibular schwannoma (VS) after treatment with fractionated stereotactic radiotherapy (FSRT) and single-session stereotactic radiosurgery (SRS) by using 3D quantitative response assessment on MRI. MATERIALS: This retrospective analysis included 162 patients who underwent radiation therapy for sporadic VS. Measurements on T1-weighted contrast-enhanced MRI (in 2-year post-therapy intervals: 0-2, 2-4, 4-6, 6-8, 8-10, 10-12 years) were taken for total tumour volume (TTV) and enhancing tumour volume (ETV) based on a semi-automated technique. Patients were considered non-responders (NRs) if they required subsequent microsurgical resection or developed radiological progression and tumour-related symptoms. RESULTS: Median follow-up was 4.1 years (range: 0.4-12.0). TTV and ETV decreased for both the FSRT and SRS groups. However, only the FSRT group achieved significant tumour shrinkage (p < 0.015 for TTV, p < 0.005 for ETV over time). The 11 NRs showed proportionally greater TTV (median TTV pre-treatment: 0.61 cm(3), 8-10 years after: 1.77 cm(3)) and ETV despite radiation therapy compared to responders (median TTV pre-treatment: 1.06 cm(3); 10-12 years after: 0.81 cm(3); p = 0.001). CONCLUSION: 3D quantification of VS showed a significant decrease in TTV and ETV on FSRT-treated patients only. NR had significantly greater TTV and ETV over time. KEY POINTS: Only FSRT not GK-treated patients showed significant tumour shrinkage over time. Clinical non-responders showed significantly less tumour shrinkage when compared to responders. 3D volumetric assessment of vestibular schwannoma shows advantages over unidimensional techniques.

Carbon nanotube-amorphous silicon hybrid solar cell with improved conversion efficiency.

We report a hybrid solar cell based on single walled carbon nanotubes (SWNTs) interfaced with amorphous silicon (a-Si). The high quality carbon nanotube network was dry transferred onto intrinsic a-Si forming Schottky junction for metallic SWNT bundles and heterojunctions for semiconducting SWNT bundles. The nanotube chemical doping and a-Si surface treatment minimized the hysteresis effect in current-voltage characteristics allowing an increase in the conversion efficiency to 1.5% under an air mass 1.5 solar spectrum simulator. We demonstrated that the thin SWNT film is able to replace a simultaneously p-doped a-Si layer and transparent conductive electrode in conventional amorphous silicon thin film photovoltaics.

Development, psychometric evaluation and validation of a brief measure of emotional preoperative stress (B-MEPS) to predict moderate to intense postoperative acute pain.

BACKGROUND: Preoperative stress might influence postoperative pain, thereby, it is desirable to assess it more precisely. Thus, we developed and evaluated the psychometric properties of a brief measure of emotional preoperative stress (B-MEPS) index using Item Response Category Characteristic Curves. We validated and assessed whether the B-MEPS can predict moderate to intense acute postoperative pain (MIAPP). METHODS: We included 863 adult patients who underwent elective surgeries (ASA I-III physical status). The B-MEPS was constructed based on items selected from instruments to assess anxiety, depression, future self-perception and minor psychiatric disorders. We identified 24 items with greatest discriminant power to identify patients who should undergo surgery to treat cancer with MIAPP. The reliability was maximized using the Cronbach's alpha indices. Fifteen items remained, which were adjusted by the Generalized Partial Credit Model. The convergent validity was assessed correlating the B-MEPS index with the pain catastrophizing (n = 100). Finally, the B-MEPS was applied in a prospective cohort of patients who underwent an abdominal hysterectomy (n = 150). RESULTS: The Cronbach's alpha for selected items was 0.83. The correlation coefficient between B-MEPS index and catastrophizing was r = 0.37 (P < 0.01). A hierarchical regression model evidenced that the B-MEPS index was a factor independent to predict MIAPP after an abdominal hysterectomy [odds ratio (OR)=1.20, confidence interval (CI) 95% 1.05-1.43). CONCLUSIONS: The B-MEPS index presents satisfactory psychometric evaluations based on its internal consistency, convergent, and discriminant validity. The B-MEPS is a propensity index to MIAPP, which might help the clinician to decide on the best therapeutic approaches for acute postoperative pain.

Repeated transcranial direct current stimulation reduces food craving in Wistar rats.

It has been suggested that food craving-an intense desire to consume a specific food (particularly foods high in sugar and fat)-can lead to obesity. This behavior has also been associated with abuse of other substances, such as drugs. Both drugs and food cause dependence by acting on brain circuitry involved in reward, motivation, and decision-making processes. The dorsolateral prefrontal cortex (DLPFC) can be activated following evocation and is implicated in alterations in food behavior and craving. Transcranial direct current stimulation (tDCS), a noninvasive brain stimulation technique capable of modulates brain activity significantly, has emerged as a promising treatment to inhibit craving. This technique is considered safe and inexpensive; however, there is scant research using animal models. Such studies could help elucidate the behavioral and molecular mechanisms of eating disorders, including food craving. The aim of our study was to evaluate palatable food consumption in rats receiving tDCS treatment (anode right/cathode left). Eighteen adult male Wistar rats were randomized by weight and divided into three groups (n = 6/group): control, with no stimulation; sham, receiving daily 30 s tDCS (500 µA) sessions for 8 consecutive days; and tDCS, receiving daily 20 min tDCS (500 µA) sessions for 8 consecutive days. All rats were evaluated for locomotor activity and anxiety-like behavior. A palatable food consumption test was performed at baseline and on treatment completion (24 h after the last tDCS session) under fasting and feeding conditions and showed that tDCS decreased food craving, thus corroborating human studies. This result confirms the important role of the prefrontal cortex in food behavior, which can be modulated by noninvasive brain stimulation.

Reexamining treatment of high-grade T1 bladder cancer according to depth of lamina propria invasion: a prospective trial of 200 patients.

BACKGROUND: Management of high-grade T1 (HGT1) bladder cancer represents a major challenge. We studied a treatment strategy according to substaging by depth of lamina propria invasion. METHODS: In this prospective observational cohort study, patients received initial transurethral resection (TUR), mitomycin-C, and BCG. Subjects with shallower lamina propria invasion (HGT1a) were followed without further surgery, whereas subjects with HGT1b received a second TUR. Association of clinical and histological features with outcomes (primary: progression; secondary: recurrence and cancer-specific survival) was assessed using Cox regression. RESULTS: Median age was 71 years; 89.5% were males, with 89 (44.5%) cases T1a and 111 (55.5%) T1b. At median follow-up of 71 months, disease progression was observed in 31 (15.5%) and in univariate analysis, substaging, carcinoma in situ, tumour size, and tumour pattern predicted progression. On multivariate analysis only substaging, associated carcinoma in situ, and tumour size remained significant for progression. CONCLUSIONS: In HGT1 bladder cancer, the strategy of performing a second TUR only in T1b cases results in a global low progression rate of 15.5%. Tumours deeply invading the lamina propria (HGT1b) showed a three-fold increase in risk of progression. Substaging should be routinely evaluated, with HGT1b cases being thoroughly evaluated for cystectomy. Inclusion in the TNM system should also be carefully considered.