Miracle-dz/UniFAR-FTUs huggingface dataset:
TRP channels as therapeutic targets in airway disorders: a patent review

Introduction: Chronic respiratory diseases, such as asthma and chronic obstructive pulmonary disease, affect millions of patients worldwide. New therapeutic approaches to these conditions are urgently needed since current treatment options provide only symptomatic relief. Transient receptor potential (TRP) ion channels are emerging molecular target candidates for the development of novel, disease-modifying drugs addressing airway diseases. Areas covered: The authors review the patent literature on novel molecules targeting TRP channels (in particular TRPA1, TRPV1, TRPM8 and TRPC6) that are currently studied in clinical trials or are candidates for future clinical evaluation in the management of respiratory diseases. Expert opinion: The patent literature highlights TRPA1 and TRPV1 channels as the most advanced therapeutic targets in respiratory disorders. TRPV1 antagonists relieve cough in preclinical studies. TRPA1 antagonists not only are anti-tussive but also show efficacy in allergic asthma models. However, to date, only minimal clinical data are available regarding the effects of selective, small-molecule TRPV1 and TRPA1 blockers in respiratory disorders. Clearly, long-term clinical studies are required to confirm the expectations based on preclinical data. In conclusion, the current status of this rapidly expanding research area raises cautious optimism for TRPA1 (and possibly also TRPV1) antagonists as promising anti-tussive/anti-asthma drug candidates.
Scaffold‐free tissue‐engineered cartilage implants for laryngotracheal reconstruction

Donor site morbidity, including pneumothorax, can be a considerable problem when harvesting cartilage grafts for laryngotracheal reconstruction (LTR). Tissue engineered cartilage may offer a solution to this problem. This study investigated the feasibility of using autologous chondrocytes to tissue‐engineer scaffold‐free cartilage grafts for LTR in rabbits to avoid degradation that often arises from an inflammatory reaction to scaffold carrier matrix.
Determinants of Utilization of Antenatal Care Services in Rural Lucknow, India

Background: Antenatal care services are the first steps towards ensuring the health of mothers and the newborn. This is the key component for achieving Millennium Development Goals by 2015. But India's performance continues to be poor in providing antenatal care services to its huge population, particularly in the rural areas. Objective: To assess the determinants of utilization of antenatal services by rural beneficiaries in Lucknow, a district of north India. Materials and Methods: The study, cross-sectional in design, was conducted from August 2009 to July 2010. Multistage random sampling was used for selecting villages. A total of 352 recently delivered women were selected following systematic random sampling. Logistic regression was used to find out the determinants of three antenatal care services. Results: Overall, 85.5% of the beneficiaries surveyed were found to receive at least three antenatal care services from any health facility. Community health centre was the most common source for such care. Significant difference was found between beneficiaries who took three antenatal care visits and who did not in terms of age, socio economic status, and timing of registration. On multiple regression, only age (OR = 2.107, 95% CI = 1.132 – 3.923) and timing of registration (OR = 2.817, 95% CI = 1.487 – 5.338) were found to be the predictors for three antenatal care visits. Conclusion: Intervention should be focused on young and late registered women for ensuring sufficient care during pregnancy.
Knowledge and practices about multidrug-resistant tuberculosis amongst healthcare workers in Maseru

Background To date, no study has been found that described the knowledge and practices of healthcare workers surrounding multidrug-resistant tuberculosis (MDR-TB) in Lesotho. Aim and setting This study was conducted to fill this gap by investigating the knowledge level and practices surrounding MDR-TB amongst healthcare workers at Botsabelo Hospital in Maseru, Lesotho. Method This was a cross-sectional survey conducted by means of a questionnaire designed specifically for this study. Data collected included sociodemographic and professional details; and responses to questions about knowledge and practices regarding MDR-TB. The questions ranged from the definition of MDR-TB to its treatment. Respondents’ practices such as the use of masks, guidelines and patient education were also assessed. Results A response rate of 84.6% (110 out of 130) was achieved. The majority of participants were women (60%), married (71.8%) and nursing staff (74.5%). Overall, less than half (47.3%) of the participants had a good level of knowledge about MDR-TB. With regard to practice, about 83% of participants stated that they used protective masks whilst attending to MDR-TB patients. About two-thirds (66.4%) reported being personally involved in educating patients about MDR-TB; whilst about 55% stated that they referred to these guidelines. Conclusion The level of knowledge about MDR-TB amongst healthcare workers at the study site was not at an acceptable level. Unsafe practices, such as not wearing protective masks and not referring to the MDR-TB treatment guidelines, were found to be associated with an insufficient level of knowledge about MDR-TB. An educational intervention is recommended for all healthcare providers at this facility.
Impact of Comorbidities on Mortality in Patients with Idiopathic Pulmonary Fibrosis

Introduction Comorbidities significantly influence the clinical course of idiopathic pulmonary fibrosis (IPF). However, their prognostic impact is not fully understood. We therefore aimed to determine the impact of comorbidities, as individual and as whole, on survival in IPF. Methods The database of a tertiary referral centre for interstitial lung diseases was reviewed for comorbidities, their treatments, their frequency and survival in IPF patients. Results 272 patients were identified of which 12% had no, 58% 1–3 and 30% 4–7 comorbidities, mainly cardiovascular, pulmonary and oncologic comorbidities. Median survival according to the frequency of comorbidities differed significantly with 66 months for patients without comorbidities, 48 months when 1–3 comorbidities were reported and 35 months when 4–7 comorbidities were prevalent (p = 0.004). A multivariate Cox proportional hazard analyses identified other cardiac diseases and lung cancer as significant predictors of death, gastro-oesophageal reflux disease (GERD) and diastolic dysfunction had a significant positive impact on survival. A significant impact of comorbidities associated therapies on survival was not discovered. This included the use of proton pump inhibitors at baseline, which was not associated with a survival benefit (p = 0.718). We also established a predictive tool for highly prevalent comorbidities, termed IPF comorbidome which demonstrates a new relationship of IPF and comorbidities. Conclusion Comorbidities are frequent in IPF patients. Some comorbidities, especially lung cancer, mainly influence survival in IPF, while others such as GERD may inherit a more favourable effect. Moreover, their cumulative incidence impacts survival.
New-onset psychosis in HIV-infected patients.

BACKGROUND Psychiatric symptoms and disorders are becoming increasingly evident in human immunodeficiency virus (HIV)-infected patients. As psychotic symptoms may be severe and require immediate behavioral management, the authors sought to determine the frequency and clinical characteristics of new-onset psychosis not obviously attributable to substance abuse or delirium in these patients. METHOD The authors reviewed the English-language literature since 1981 by means of the Index Medicus and MEDLINE for reports of new-onset psychosis in HIV-infected patients and also examined the charts of 124 HIV-infected patients who had been followed up at the San Diego Veterans Affairs Medical Center since 1984. Cases of substance-induced psychosis and delirium were excluded. RESULTS Results reflect a combination of cases from the authors' study and cases of new-onset HIV-associated psychosis reported in the literature (N = 31). Results of the initial neurologic evaluation, including computed tomography (CT) scan and examination of the CSF, were normal in a majority of patients (CT = 12 of 23 patients; CSF = 10 of 14 patients). Psychotic symptoms improved with neuroleptic treatment although side effects were frequently seen. In some patients (N = 12) psychosis was the presenting manifestation of HIV infection or acquired immunodeficiency syndrome. A proportion of patients (N = 7 [23%]), especially those with an abnormal CT and EEG at the time of presentation with psychosis, tended to have a relatively rapid deterioration in cognitive and medical status. Differences between studies in population and method made it impossible to determine the frequency of new-onset psychosis in the general HIV-infected population. CONCLUSIONS A common clinical feature noted in new-onset psychosis in HIV-infected patients was acute or subacute onset of symptoms, which included delusions, hallucinations, bizarre behavior, mood or affective disturbances, and mild memory or cognitive impairment. The etiological association of the HIV infection to the psychosis is yet to be established.
Heparin‐Coated Cardiopulmonary Bypass Circuit: Clinical Effects in Pediatric Cardiac Surgery

Abstract Objectives: Heparin‐coated cardiopulmonary bypass (CPB) circuits have been reported to reduce complement activation and the inflammatory response associated with CPB. We retrospectively compared patients utilizing heparin‐coated perfusion circuits with those using noncoated circuits to determine the clinical effects of the different circuits in pediatric cardiac surgery. Methods: Between July 1995 and July 1997, 203 patients weighing < 10 kg underwent cardiac surgery, 153 patients using heparin‐coated bypass circuits and 50 patients using noncoated circuits. The 50 patients operated on with the noncoated circuit (Group N) were matched to 100 patients operated on with coated circuits (Group H) in age, weight, and type of procedure. Urine output during bypass, blood products used after bypass, postoperative ventilation days, hospital stay, morbidity, and mortality were compared between these groups. Results: Body weight, perfusion time, and procedure time were not different between the two groups. Urine output during bypass was notably greater in Group H than in Group N (11.3 ± 10.5 mL/kg per hour vs 4.8 ± 3.1 mL/kg per hour, respectively, p < 0.0001). Postoperative mechanical ventilation markedly decreased in Group H (Group H vs N = 2.8 ± 2.7 days vs 5.1 ± 7.5 days, respectively, p < 0.05). Red blood cell usage, hospital stay, morbidity, and mortality were not statistically different, although there was a tendency toward decreased transfusion of red cell and platelets in Group H (Group H vs N = 61.2 ± 121.1 mL/kg vs 102.0 ± 176.7 mL/kg, respectively, in red cell, p = 0.15; and Group H vs N = 7.9 ± 13.7 mL/kg vs 13.2 ± 24.5 mL/kg, respectively, in platelets, p = 0.16). Conclusions: Patients operated on with the use of heparin‐coated circuits had increased urine output during bypass and required less time postoperatively on the ventilator. These results suggest a reduction in the acute inflammatory response, capillary leakage, and overall systemic edema. We now routinely use coated circuits on all pediatric pump cases.
Emerging from their burrow: Hedgehog pathway inhibitors for cancer

ABSTRACT Introduction: Cancer treatment is moving away from conventional cytotoxic drugs and towards agents that target specific proteins and mechanisms important to cancer development or survival. The Hedgehog Pathway (HhP) is a signal transduction pathway and its constitutive activation is tumorigenic in basal cell carcinoma (BCC). The HhP enables phenotypic flexibility, and channels tumor-stroma interactions. As a result, it is over-expressed in numerous cancers as well as in the tumor microenvironment and may represent a promising therapeutic target. Areas covered: In this article, we review the rationale for targeting HhP and its role as an oncogenic driver, in tumor epithelial-to-mesenchymal transition (EMT), and in the tumor microenvironment and describe the results of preclinical and clinical studies involving HhP inhibitors. Expert opinion: HhP activation plays an important role in both the tumor microenvironment and tumor EMT which can lead to treatment resistance for a number of different malignancies. In addition to standard use in BCC, several HhP inhibitors are in preclinical, early, and mid-stage clinical development for other solid and hematologic malignancies.
Regulation of the glucose:H+ symporter by metabolite-activated ATP-dependent phosphorylation of HPr in Lactobacillus brevis

Lactobacillus brevis takes up glucose and the nonmetabolizable glucose analog 2-deoxyglucose (2DG), as well as lactose and the nonmetabolizable lactose analoge thiomethyl beta-galactoside (TMG), via proton symport. Our earlier studies showed that TMG, previously accumulated in L. brevis cells via the lactose:H+ symporter, rapidly effluxes from L. brevis cells or vesicles upon addition of glucose and that glucose inhibits further accumulation of TMG. This regulation was shown to be mediated by a metabolite-activated protein kinase that phosphorylase serine 46 in the HPr protein. We have now analyzed the regulation of 2DG uptake and efflux and compared it with that of TMG. Uptake of 2DG was dependent on an energy source, effectively provided by intravesicular ATP or by extravesicular arginine which provides ATP via an ATP-generating system involving the arginine deiminase pathway. 2DG uptake into these vesicles was not inhibited, and preaccumulated 2DG did not efflux from them upon electroporation of fructose 1,6-diphosphate or gluconate 6-phosphate into the vesicles. Intravesicular but not extravesicular wild-type or H15A mutant HPr of Bacillus subtilis promoted inhibition (53 and 46%, respectively) of the permease in the presence of these metabolites. Counterflow experiments indicated that inhibition of 2DG uptake is due to the partial uncoupling of proton symport from sugar transport. Intravesicular S46A mutant HPr could not promote regulation of glucose permease activity when electroporated into the vesicles with or without the phosphorylated metabolites, but the S46D mutant protein promoted regulation, even in the absence of a metabolite. The Vmax but not the Km values for both TMG and 2DG uptake were affected. Uptake of the natural, metabolizable substrates of the lactose, glucose, mannose, and ribose permeases was inhibited by wild-type HPr in the presence of fructose 1,6-diphosphate or by S46D mutant HPr. These results establish that HPr serine phosphorylation by the ATP-dependent, metabolite-activated HPr kinase regulates glucose and lactose permease activities in L. brevis and suggest that other permeases may also be subject to this mode of regulation.
Autologous Chondrocyte Implantation of the Ankle

Background: The treatment of osteochondral lesions of the talus after failed surgery is challenging, with no clear solution. Short-term results using autologous chondrocyte implantation have been promising. Purpose: To report the long-term outcomes of patients who underwent autologous chondrocyte implantation (ACI) of the talus after failed marrow stimulation techniques for osteochondral lesions of the talus (OLTs). Study Design: Case series; Level of evidence, 4. Methods: Thirty-two consecutive patients underwent ACI of the talus, and 29 patients (15 male, 14 female; mean age, 34 years [range, 16-54 years]) were available for follow-up. There were 23 medial and 6 lateral lesions, with a mean size of 18 × 11 mm (198 mm2; range, 80-500 mm2). Twenty patients underwent ACI of the talus alone; 9 underwent ACI with bone grafting of underlying cysts. Follow-up was performed at a mean of 70 months (range, 24-129 months). Patient outcomes were evaluated using the simplified symptomatology score, Tegner activity score, Finsen score, and American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score. Twenty-five patients (86%) underwent second-look arthroscopic surgery at the time of hardware removal and were assessed with the International Cartilage Repair Society (ICRS) score. Postoperative magnetic resonance imaging (MRI) was performed on 24 patients (83%) and compared with preoperative MRI scans. Results: Preoperatively, 26 patients rated their ankles as poor and 3 as fair using the simplified symptomatology score. At last follow-up, 9 were classified as excellent, 14 as good, 5 as fair, and 1 as poor using the same score. The mean AOFAS score improved from 50.1 to 85.9 (range, 65-100). The mean Tegner activity score improved from 1.6 to 4.3 (P < .0001). The mean Finsen score (modified Weber score) showed significant improvement from 13.7 to 5.1 (P < .0001). Conclusion: Autologous chondrocyte implantation of the talus yields improvement in all parameters tested with enduring long-term results in patients who have failed previous surgery for OLTs.
Use of the International Classification of Functioning, Disability and Health for monitoring patients using cochlear implants.

PURPOSE To characterize the profile of patients with cochlear implant as proposed by the International Classification of Functioning, Disability and Health for Children and Youth (ICF-CY). METHODS This is a descriptive, cross-sectional retrospective study, which examined 30 medical records of patients using the cochlear implant of Centro de Pesquisas Audiológicas; To characterize the profile of the patients, the ICF-CY was used. Regarding the assessment, researchers relied on procedures performed in clinical routine, besides information registered in the medical record. After reviewing the information, it was related to codes from the ICF-CY; with the addition of a qualifier afterwards. RESULTS Overall, 55 codes from the ICF were related to the instruments to characterize this population. Regarding the Body Functions field, most participants did not have disabilities related to reception and expression of oral language and auditory functions, with only written language disabilities being found. These same findings were observed in the Activity and Participation Field. Regarding environmental factors, noise and the non-availability of technology resources to assist in the auditory comprehension of noise were characterized as a barrier, as well as the absence of speech therapy. CONCLUSION This study concluded that most of the participating children showed no deficiency in the body functions, with difficulties being only reported in relation to school performance. Environmental factors (noise, non-availability of technological resources, absence of speech therapy) were characterized as a barrier. The need to expand assessments in the clinical routine was also noted.
Aberrant Recruitment and Activation of T Cells in Diabetic Nephropathy

Background/Aims: Recent evidence has shown that an inflammatory process is involved in the development and progression of diabetic nephropathy. This study examined the impact of activated intrarenal lymphocytes in this inflammatory process. Methods: We studied T cell recruitment in mice with streptozotocin (STZ)-induced diabetes by flow cytometry and immunohistochemistry. The kidney biopsy specimens from patients with type 2 diabetes mellitus and diabetic nephropathy were evaluated by immunohistochemistry. Results: In flow cytometry, intrarenal CD3+ T cells were significantly increased in proteinuric mice at 20 weeks after STZ injection. However, the population of T cells and B cells in diabetic spleen was not different from that of control mice. Immunohistochemistry also showed a marked infiltration of interstitial CD4+, CD8+ T cells in diabetic kidney. Interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) mRNA expression was significantly increased in diabetic mouse kidney compared with controls. Interestingly, flow cytometry analysis of kidney-derived mononuclear cells from diabetic mice showed significantly increased production of IFN-γ and TNF-α by CD3+ T cells. Type 2 diabetic patients also showed a marked increase in CD4+, CD8+ and CD20+ cells in interstitium, and the number of CD4+ and CD20+ cells correlated with the amount of proteinuria. Conclusion: Our results clearly showed that aberrant intrarenal infiltration and the activation of T cells in interstitium are the underlying immunopathological mechanisms of diabetic kidney injury.
The Social Underpinnings of Decentralized Governance

Accountable governance is defined by four elements: First, the definition of interests on the part of citizens and groups of citizens; second, the aggregation or accumulation of those interests via some “technology”, whether it be by an election, lobby, or social media; third, the translation of those preferences into government behavior; and fourth, a means whereby citizens can evaluate the quality of government behavior. Decentralization has the potential to impact each of these links. Most of the rigorous thinking on how it does so has been institutional in nature. In other words, it has focused on how formal rules governing elections, leadership selection, fiscal federalism, etc. impact political accountability. Donor programming and accompanying impact evaluations, on the other hand, have focused less on institutions and more on mobilizing civil society and “social accountability”, i.e. on approaches to informing and mobilizing citizens such that they might become better participants in politics. These programming efforts have progressed with considerable normative enthusiasm but without, for the most part, reference to recent academic breakthroughs on the social conditions for cooperative behavior and collective action. The goal of this chapter is to consider how recent innovations in the study of information flows and cooperation in social networks might inform donor programming on social accountability. Research on social networks provides insights into the relational characteristics of communities that are certain to impact the prospects for accountability, and gives rigorous underpinnings into the frequent, if underspecified, claim that “context matters”.
Male combat veterans' narratives of PTSD, masculinity, and health.

This article uniquely examines the ways a group of male combat veterans talk about masculinity and how, following post-traumatic stress disorder (PTSD), they performed masculinities in the context of a surfing group, and what effects this had upon their health and wellbeing. Participant observations and life history interviews were conducted with a group of combat veterans who belonged to a surfing charity for veterans experiencing PTSD. Data were rigorously explored via narrative analysis. Our findings revealed the ways in which veterans enacted masculinities in accordance with the values that were cultivated during military service. These masculine performances in the surfing group had important effects both on and for the veterans' wellbeing. Significantly, the study highlights how masculine performances can be seen alternately as a danger and as a resource for health and wellbeing in relation to PTSD. The article advances knowledge on combat veterans and mental health with critical implications for the promotion of male veterans' mental health. These include the original suggestion that health-promoting masculine performances might be recognised and supported in PTSD treatment settings. Rather than automatically viewing masculinity as problematic, this article moves the field forward by highlighting how hegemonic masculinities can be reconstructed in positive ways which might improve veterans' health and wellbeing. A video abstract of this article can be found at: https://www.youtube. com/watch? v=BaYzaOP1kAY.