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Chronic wounds are a major global health problem with the presence of biofilm significantly contributing to wound chronicity. Current treatments are ineffective in resolving biofilm and simultaneously killing the bacteria; therefore, effective biofilm-resolving drugs are needed. We have previously shown that, together with α-tocopherol, N-acetyl-cysteine (NAC) significantly improves the healing of biofilm-containing chronic wounds, in a diabetic mouse model we developed, by causing disappearance of the bacteria and breakdown of the extracellular polymeric substance (EPS). We hypothesize that NAC creates a microenvironment that affects bacterial survival and EPS integrity. To test this hypothesis, we developed an in vitro biofilm system using microbiome taken directly from diabetic mouse chronic wounds. For these studies, we chose mice in which chronic wound microbiome was rich in Pseudomonas aeruginosa (97%). We show that NAC at concentrations with pH < pKa causes bacterial cell death and breakdown of EPS. When used before biofilm is formed, NAC leads to bacterial cell death whereas treatment after the biofilm is established NAC causes biofilm dismantling accompanied by bacterial cell death. Mechanistically, we show that NAC can penetrate the bacterial membrane, increase oxidative stress, and halt protein synthesis. We also show that low pH is important for the actions of NAC and that bacterial death occurs independently of the presence of biofilm. In addition, we show that both the acetyl and carboxylic groups play key roles in NAC functions. The results presented here provide insight into the mechanisms by which NAC dismantles biofilm and how it could be used to treat chronic wounds after debridement (NAC applied at the start of culture) or without debridement (NAC applied when biofilm is already formed). This approach can be taken to develop biofilm from microbiome taken directly from human chronic wounds to test molecules that could be effective for the treatment of specific biofilm compositions.

Introduction Various surgical modalities have been tried for the correction of chronic recurrent dislocation of the temporomandibular joint. However, most of these techniques are aimed at creating an artificial block or removing any interference in the path of the translating condyle. Chronic dislocation can also be classified as meniscotemporal and menisocondylar, depending upon whether the dislocation occurs between the condyle–disc unit and temporal bone (meniscotemporal), or between the disc and condyle (meniscocondylar). Very few procedures address the primary issue of a malpositioned disc, which is the cause of meniscocondylar dislocation. Materials and Methods This study was conducted on 17 patients (27 joints) who reported with chronic dislocation of the temporomandibular joint, with MRI-proven meniscocondylar dislocation. After exposure of the condyle and disc through a standard pre-auricular incision, an orthodontic mini-screw was fixed to the posterior aspect of the condylar head and a 1-0 Prolene suture passed through the screw-head eyelet, plicating the posterior edge of the disc to the condyle. This ensured that the condyle and disc would move in unison. Results All the patients showed improvement in their symptoms of dislocation in the postoperative period, including seven patients in whom only a unilateral procedure was carried out. None of the patients had any recurrence till the 1-year followup. Conclusion Our procedure addresses the fundamental etiology of meniscocondylar dislocation by anchoring the disc to the condyle by using an orthodontic mini-implant and correcting the condyle–disc disharmony. This technique is reliable, technically feasible, and cost-effective in the Indian set up.

Introduction Mucosal malignant melanoma of the anorectum is a rare and aggressive disease, in which early diagnosis is difficult. The prognosis remains extremely poor, irrespective of the treatment. We share our experience in treating this malignancy at our centre in South India. Methods This study describes a retrospective analysis of 31 cases of anorectal melanoma presented to our centre between January 2001 and December 2013. Results Twenty-two patients (71%) presented with metastasis and had a median overall survival of nine months. None of the 22 patients survived for two years. Nine patients (29%) had curative surgery, in the form of abdominoperineal resection (six patients), abdominoperineal resection with bilateral inguinal node dissection (one patient), abdominoperineal resection with liver resection (one patient) and posterior exenteration (one patient). In patients who underwent curative surgery, the median overall survival was 15 months and disease-free survival was nine months, with a two-year overall survival of 22%. Conclusions Anorectal melanoma is an aggressive disease with a poor prognosis. The majority of patients present with distant metastases. Prognosis depends on stage at presentation. Early diagnosis and surgical resection may improve the overall outcome. Newer modalities such as immunotherapy and targeted therapies such as anti-CTLA4 monoclonal antibody and anti-programmed cell death protein 1 monoclonal antibodies have radically changed the management of mucosal melanoma and may, in the future, improve the overall prognosis of anorectal melanoma.

Incidence of Buxtonella sulcata was recorded as 20.9 % in bovines (n = 374) of R.S. Pura, Jammu with cattle showing higher infection rate (23.6 %) than the buffaloes (18.5 %). The infection was significantly (p < 0.0001) higher in young animals (33.1 %) than the adults (13.9 %). Animals with diarrhoeic faeces had a significantly higher (p < 0.0001) infection rate (38.5 %) than the animals with normal faeces (9.9 %), suggesting the influence of protozoan on the incidence of diarrhoeal symptoms in bovines.

Internet-accessed sexually transmitted infection testing (e-STI testing) is increasingly available as an alternative to testing in clinics. Typically this testing modality enables users to order a test kit from a virtual service (via a website or app), collect their own samples, return test samples to a laboratory, and be notified of their results by short message service (SMS) or telephone. e-STI testing is assumed to increase access to testing in comparison with face-to-face services, but the evidence is unclear. We conducted a randomised controlled trial to assess the effectiveness of an e-STI testing and results service (chlamydia, gonorrhoea, HIV, and syphilis) on STI testing uptake and STI cases diagnosed. The study took place in the London boroughs of Lambeth and Southwark. Between 24 November 2014 and 31 August 2015, we recruited 2,072 participants, aged 16-30 years, who were resident in these boroughs, had at least 1 sexual partner in the last 12 months, stated willingness to take an STI test, and had access to the internet. Those unable to provide consent and unable to read English were excluded. Participants were randomly allocated to receive 1 text message with the web link of an e-STI testing and results service (intervention group) or to receive 1 text message with the web link of a bespoke website listing the locations, contact details, and websites of 7 local sexual health clinics (control group). Participants were free to use any other services or interventions during the study period. The primary outcomes were self-reported STI testing at 6 weeks, verified by patient record checks, and self-reported STI diagnosis at 6 weeks, verified by patient record checks. Secondary outcomes were the proportion of participants prescribed treatment for an STI, time from randomisation to completion of an STI test, and time from randomisation to treatment of an STI. Participants were sent a £10 cash incentive on submission of self-reported data. We completed all follow-up, including patient record checks, by 17 June 2016. Uptake of STI testing was increased in the intervention group at 6 weeks (50.0% versus 26.6%, relative risk [RR] 1.87, 95% CI 1.63 to 2.15, P < 0.001). The proportion of participants diagnosed was 2.8% in the intervention group versus 1.4% in the control group (RR 2.10, 95% CI 0.94 to 4.70, P = 0.079). No evidence of heterogeneity was observed for any of the pre-specified subgroup analyses. The proportion of participants treated was 1.1% in the intervention group versus 0.7% in the control group (RR 1.72, 95% CI 0.71 to 4.16, P = 0.231). Time to test, was shorter in the intervention group compared to the control group (28.8 days versus 36.5 days, P < 0.001, test for difference in restricted mean survival time [RMST]), but no differences were observed for time to treatment (83.2 days versus 83.5 days, P = 0.51, test for difference in RMST). We were unable to recruit the planned 3,000 participants and therefore lacked power for the analyses of STI diagnoses and STI cases treated. The e-STI testing service increased uptake of STI testing for all groups including high-risk groups. The intervention required people to attend clinic for treatment and did not reduce time to treatment. Service innovations to improve treatment rates for those diagnosed online are required and could include e-treatment and postal treatment services. e-STI testing services require long-term monitoring and evaluation. ISRCTN Registry ISRCTN13354298.

For a discrete-time finite-state Markov chain, we develop an adaptive importance sampling scheme to estimate the expected total cost before hitting a set of terminal states. This scheme updates the change of measure at every transition using constant or decreasing step-size stochastic approximation. The updates are shown to concentrate asymptotically in a neighborhood of the desired zero-variance estimator. Through simulation experiments on simple Markovian queues, we observe that the proposed technique performs very well in estimating performance measures related to rare events associated with queue lengths exceeding prescribed thresholds. We include performance comparisons of the proposed algorithm with existing adaptive importance sampling algorithms on some examples. We also discuss the extension of the technique to estimate the infinite horizon expected discounted cost and the expected average cost.

The poor quality and limited extent of palliative care services are of concern across the globe. To identify and measure patients' symptoms in Nepal, using a cell phone questionnaire platform, the investigators conducted and previously reported a cross-sectional study of Nepali adults. The unreported details of pain and other symptoms in these study data are here considered together with possible explanations and implications for interventions to lessen these symptoms. In a \"snapshot\" cross-sectional study of patients under regular care in three tertiary care Nepalese centers, we questioned 383 patients with incurable cancers using a 15-item cell phone-validated instrument to describe their major current symptoms and their intensities. The distributions of 11 symptom-level scores and the correlations between pain and different symptom scores were determined. Thirty-eight percent of the population (142/383) had maximal pain scores which were in the severe range, and 25% (97/383) had such scores where they were evaluated. Patients reported moderate-to-severe tiredness 48% (183/383), depression 45% (172/383), anxiety 56% (217/383), poor appetite 64% (246/383), sleep quantity 64% (246/383), and sleep quality 64% (247/383). The significant fractions of patients with severe maximal and at-evaluation pain scores suggest that inadequate recognition and treatment of such symptoms characterized care of these regularly seen patients. The high fractions of patients with mood and sleep disturbances support this reading, suggesting helplessness and hopelessness, all addressable with psychosocial, environmental, and nontoxic, inexpensive pharmacological interventions.

Background Research has shown that mobile phone contraceptive behavioral interventions can increase knowledge and use of contraception, but other studies have failed to demonstrate a beneficial effect. The objective of this trial was to estimate the effect of a contraceptive behavioral intervention delivered by mobile phone text message on young Palestinian women’s attitudes towards effective contraception. Methods We conducted a randomized controlled trial among women aged 18–24 years living in the West Bank, who were not using an effective method of contraception. The intervention group received zero to three messages per day (113 messages for female-not married and 120 messages for female-married) for 120 days. The control group received 16 messages over 120 days about trial participation. The primary outcome was acceptability of at least one method of effective contraception at 4 months. Secondary outcomes were use of effective contraception at 4 months and any use during the study, acceptability of individual methods, service uptake, unintended pregnancy and abortion. Process outcomes included knowledge, perceived norms, personal agency and intention. All outcomes were self-reported. We analyzed the outcomes using logistic and linear regression. Results A total of 578 participants were enrolled and 464 (80%) completed follow up at 4 months. Intervention group participants were more likely to find at least one method of effective contraception acceptable (31% in the intervention group versus 17% in the control group, adjusted OR 2.34, 95% CI 1.48–3.68, p  < 0.001). They had a higher mean knowledge score, were more likely to find the intrauterine device, injection, implant and patch acceptable, to agree that their friends would use an effective method and to intend to use an effective method, compared to participants in the control group. While in the direction of intervention benefit, there were no differences between the groups in the use of effective contraception at 4 months and any use during the study, pill acceptability, service uptake, unintended pregnancy and induced abortion. Conclusions The intervention can improve attitudes, knowledge-perceived norms and intention to use effective contraception among young women in Palestine. Research is needed to evaluate the efficacy of the intervention for contraceptive behavioral outcomes in Palestine. Trial registration ClinicalTrials.gov, NCT02905461 . Registered on 14 September 2016. World Health Organization Trial Registration Data Set: http://apps.who.int/trialsearch/Trial2.aspx?TrialID=NCT02905461

There is paucity of data available on how chronic kidney disease (CKD) is treated before referral to a tertiary hospital. This study was conducted to assess pre-tertiary hospital care of patients with CKD 5 at their presentation to nephrology services at a tertiary care hospital. Over a period of 8 months, consecutive patients with CKD 5 presenting at the Nephrology services at Christian Medical College, Vellore, Tamil Nadu, and their relatives were interviewed to assess the pre-tertiary hospital care and knowledge about CKD 5 and its treatment. A total of 561 patients with CKD 5 were enrolled. The mean duration (months) of known CKD was 12.4 +/- 23.1 and known CKD 5 was 3.2 +/- 3.5. Of these, 369 patients (65.8%) had been under the care of a nephrologist; 305 patients had CKD 5 as the initial presentation of renal illness. Vaccination against hepatitis B had been initiated in only 133 patients (23.7%). Only 172 patients(38%) had an adequately controlled blood pressure. Care under a nephrologist was more likely to result in appropriate investigation, treatment and patient education though blood pressure control did not differ. Paucity of symptoms in the initial stages of certain forms of CKD probably led to 50 per cent of patients presenting with CKD 5 as the initial presentation of renal disease. Inadequate vaccination against hepatitis B infection highlights the need for appropriate vaccination. Prevention of CKD and its progression are important targets which requires physician awareness at all levels. Early referral to a nephrologist's care is more likely to result in appropriate investigations and treatment.

Healthcare facility is scarce for rural women in the developing world. The situation is worse for patients who are suffering from diseases that require long-term feedback-oriented monitoring such as breast cancer. Lack of motivation to go to the health centers on patients’ side due to sociocultural barriers, financial restrictions and transportation hazards results in inadequate data for proper assessment. Fortunately, mobile phones have penetrated the masses even in rural communities of the developing countries. In this scenario, a mobile phone-based remote symptom monitoring system (RSMS) with inspirational videos can serve the purpose of both patients and doctors. Here, we present the findings of our field study conducted on 39 breast cancer patients in rural Bangladesh. Based on the results of extensive field studies, we have categorized the challenges faced by patients in different phases of the treatment process. As a solution, we have designed, developed and deployed e-ESAS—the first mobile-based RSMS in rural context. Along with the detail need assessment of such a system, we describe the evolution of e-ESAS and the deployment results. We have included the unique and useful design lessons that we learned as e-ESAS evolved through participatory design process. The findings show how e-ESAS addresses several challenges faced by patients and doctors and positively impact their lives.