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Background Neonatal infection is infection of the newborn or neonate acquired in first four weeks of life or during prenatal development. Microorganism associated neonatal infections caused severe mortality in recent years. It is developed either prenatally or within 28 days of neonatal period. This infection is mainly transmitted from mother to child through placenta. It has been well associated with the premature rupture of membranes which markedly enhances the risk of neonatal sepsis. Methods The present experiment was designed to analyze bacteria, their antibiotic resistance pattern and possible risk factors among neonatal patients with sepsis. The neonates specimen was subjected for the isolation of bacteria and antibiotic susceptibility test. Neonates were analyzed with previous clinical history such as, previous admission in hospitals, mode of delivery, birth weight, and feeding type in accordance with questionnaire. Results Gram-positive bacteria isolates were found to be high (79 strains, 64.22%) than the Gram-negative bacteria (44 strains, 32.5%). Staphylococcus aureus (33 strains, 26.9%) was the major Gram-positive groups of bacteria. Multidrug resistance analysis accounted more S. aureus (26.9%) and 5 strains (15.15%) showed methicillin resistance, whereas 84.9% were found to be sensitive to methicillin. Conclusion In this study, S. aureusand K. pneumoniae were the highest frequency of isolates. The overall percentage of multidrug resistant isolates was high in this study. Highest degree of resistance was observed in ampicillin against all isolates. Hence much attention is required while diagnosing sepsis among neonates. To analyze the risk for neonatal sepsis, it is not preferable for caesarian mode of delivery. Moreover, frequent screening of mother, suitable prenatal care of newborns with proper clinical interventions isthe key elements to control sepsis.

The objective of the study: to assess the efficacy of complex treatment with endobronchial valve implantation in the patients suffering from drug resistant fibrous cavernous pulmonary tuberculosis.Subjects and methods. Treatment outcomes in 97 patients with limited fibrous cavernous pulmonary tuberculosis were analyzed. Main Group included 42 patients who had bronchial valve block implanted. Comparison Group included 55 patients. Artificial pneumoperitoneum was used in both groups.Results. In Main Group, sputum conversion was achieved in 12 months in 40 (95.2%) patients, and in 32 patients (58.2%) in Comparison Group (p < 0.01). In 12 months after treatment start, positive X-ray changes were observed in 42 (100%) patients of Main Group and 40 (72.7%) patients of Comparison Group. Healing of cavities in 12 months was observed only in the patients from Main Group (26 (61.9%) patients). Upon completion of the study, surgery was still indicated to 4 (9.5%) of patients from Main Group and to 35 (63.6%) patients from Comparison Group.

Background & objectives: There is a need for an affordable, easy, high-sensitivity test usable at the peripheral health facility for diagnosis of drug-resistant (DR) tuberculosis (TB) to interrupt disease transmission. Nucleic acid amplification tests (NAATs) for early detection of DR-TB are ideal to bring testing near to the patient. TruenatTM MTB (Mycobacterium tuberculosis) and TruenatTM MTB-RIF (rifampicin) is an indigenous chip-based real-time polymerase chain reaction (PCR) based test for detection of multidrug-resistant (MDR) TB. The test involves extraction of DNA using automated, battery operated Trueprep instrument and real-time PCR performed on the Truelab analyzer. We report here multicentric validation of Truenat MTB-RIF for detection of DR-TB in suspected DR-TB patients. Methods: Consecutive patients aged 18-65 yr, with symptoms suggestive of TB and with a history of previous treatment, reporting to the National TB Elimination Programme (NTEP) clinics under four national institutes, namely AIIMS (All India Institute of Medical Sciences, New Delhi), NITRD (National Institute of Tuberculosis and Respiratory Diseases, New Delhi), NIRT (National Institute for Research in Tuberculosis, Chennai) and ICMR-National JALMA Institute for Leprosy and other Mycobacterial Diseases, Agra, were included in the study. Two sputum samples (one spot and one morning) were collected from each patient, after obtaining informed written consent. The samples were subjected to smear, GeneXpert and MGIT 960 culture (and drug susceptibility testing to RIF) (surrogate for MDR-TB) to serve as reference tests. The samples were coded to ensure blinding and subjected to Truenat MTB-RIF. Truenat MTB-RIF Version 1.5 was used for testing 1084 samples for RIF resistance, while Version 2.0 was used to test another 1201 samples. Results: Truenat MTB-RIF Version 1.5 in comparison with comprehensive laboratory reference standards yielded sensitivity and specificity of 76.2 and 94.7 per cent, respectively for the detection of RIF resistance in 1084 samples, collected across four sites. Based on the analysis of discordant samples, Version 2.0 of Truenat was developed by the manufacturer and this was further tested on additional 1201 samples, yielding a sensitivity of 87.5 per cent and specificity of 99.5 per cent. Interpretation & conclusions: Multicentric trial of TruenatTM MTB-RIF demonstrated a great potential of this point of care NAAT for detection of MDR-TB. The test would be useful in limited resource settings and inaccessible areas without need for any additional infrastructure.

Background: Appropriate technology tests are needed for Mycobacterium tuberculosis drug-susceptibility testing (DST) in resource-constrained settings. This study was performed to evaluate the MDR/XDR-TB Colour Test (a colour platethin-layer agar test; TB-CX) for M. tuberculosis DST by directly testing sputum at University of Gondar Hospital. Methods: Sputum samples were each divided into two aliquots. One aliquot was mixed with disinfectant and applied directly to the TB-CX quadrant petri-plate containing culture medium with and without isoniazid, rifampicin, or ciprofloxacin. Concurrently, the other aliquot was decontaminated with sodium hydroxide, centrifuged, and cultured on Lӧwenstein–Jensen medium; the stored M. tuberculosis isolates were then sub-cultured in BACTEC Mycobacteria Growth Indicator Tube (MGIT) 960 for reference DST. Results: The TB-CX test yielded DST results for 94% (123/131) of positive samples. For paired DST results, the median number of days from sputum processing to DST was 12 for TB-CX versus 35 for LJ-MGIT (p

Joseph Baruch Baluku,1,2 Sharon Namiiro,2 Martin Nabwana,3 Winters Muttamba,2 Bruce Kirenga2 1Division of Pulmonology, Kiruddu National Referral Hospital, Kampala, Uganda; 2Research and Innovation Department, Makerere University Lung Institute, Kampala, Uganda; 3Quality Management Division, Makerere University – Johns Hopkins University Research Collaboration, Kampala, UgandaCorrespondence: Joseph Baruch BalukuKiruddu National Referral Hospital, Kampala, UgandaTel +256706327972Email bbjoe18@gmail.comBackground: Undernutrition is associated with unfavourable treatment outcomes among people with drug-resistant tuberculosis (DRTB). Factors influencing the treatment outcomes among undernourished people with DRTB are not well characterised. The aim of this study was to determine factors associated with treatment success among undernourished people with DRTB in Uganda.Methods: We analysed data from a retrospective cohort of people with DRTB from 16 treatment sites in Uganda. We included participants with a pre-treatment body mass index (BMI) of < 18.5 kilograms/meters2 (kg/m2). Participants were categorised as having mild (BMI of 18.5– 17 kg/m2), moderate (BMI of 16.9– 16.0 kg/m2) or severe (BMI of < 16.0 kg/m2) undernutrition. We performed logistic regression analysis to determine factors associated with treatment success.Results: Among 473 people with DRTB, 276 (58.4%) were undernourished (BMI < 18.5 Kg/m2) and were included in the study. Of these, 92 (33.3%) had mild, 69 (25.0%) had moderate and 115 (41.7%) had severe undernutrition. The overall treatment success rate (TSR) for the undernourished was 71.4% (n = 197). Although the TSR was similar among participants with mild (71.7%), moderate (78.3%) and severe (67.0%) undernutrition (p = 0.258), all treatment failure cases (n =6) were among participants with severe undernutrition (p = 0.010). Cigarette smoking (odds ratio (OR) = 0.19, 95% CI 0.07– 0.47, p < 0.001), urban residence (OR = 0.31, 95% CI 0.14– 0.70, p = 0.005) and moderate (OR = 0.14, 95% CI 0.06– 0.35, p < 0.001) and severe anaemia (OR = 0.06, 95% CI 0.01– 0.29, p = 0.001) were associated with lower odds of treatment success.Conclusion: Most undernourished people with DRTB have severe undernutrition. Smoking and anaemia are modifiable factors which upon appropriate intervention could improve treatment success. The effect of urban residence on the TSR needs to be evaluated further.Keywords: MDR TB, undernutrition, malnutrition, drug resistant, tuberculosis, anaemia

Multiple myeloma (MM) is a plasma cells neoplasm. The overexpression of Bcl-2 family proteins, particularly myeloid cell leukemia 1 (Mcl-1), plays a critical role in the pathogenesis of MM. The overexpression of Mcl-1 is associated with drug resistance and overall poor prognosis of MM. Thus, inhibition of the Mcl-1 protein considered as a therapeutic strategy to kill the myeloma cells. Over the last decade, the development of selective Mcl-1 inhibitors has seen remarkable advancement. This review presents the critical role of Mcl-1 in the progression of MM, the most prominent BH3 mimetic and semi-BH3 mimetic that selectively inhibit Mcl-1, and could be used as single agent or combined with existing therapies.

Background: Multidrug-resistant tuberculosis (MDR-TB) is a global health problem with notoriously difficult and challenging treatment. This study determined treatment outcome in patients of MDR-TB with modified DOTS-Plus strategy. Methods: Ninety-eight consecutive MDR-TB patients treated with standardized regimen according to modified DOTS-Plus strategy aligned to the existing national DOTS-Plus guidelines with relevant modifications proposed by Chennai consensus were analyzed prospectively. Treatment included monthly follow-up with clinical, radiological, and bacteriological assessment (sputum smear advised monthly till conversion then quarterly; culture for Mycobacterium tuberculosis at 0, 4, 6, 12, 18, and 24 months), ensuring adherence, intense health education, and monitoring of adverse events (AEs). Patients' outcome was considered as cure when at least two of the last three cultures (all three or last two) were negative and as failure when the same were positive. Results: Favorable and unfavorable outcomes in this cohort were reported to be 71/98 (72.4%) and 27/98 (27.6%) (failure – 10 [10.2%], default – 7 [7.1%], and expiry – 10 [10.2%]), respectively. Sputum smear and culture conversion rate were 75/81 (92.5%) and 71/81 (87.7%), respectively. Major AEs were experienced in only 17.4% of patients. Conclusions: MDR-TB can be cured successfully with modified DOTS-Plus strategy and requires much effort from both the patients and health-care workers. It can be an alternative model for treating MDR-TB patients in private sector.

Background: Comorbid conditions and adverse drug events are associated with poor treatment outcomes among patients with drug resistant tuberculosis (DR – TB). This study aimed at determining the treatment outcomes of DR – TB patients with poor prognostic indicators in Uganda. Methods: We reviewed treatment records of DR – TB patients from 16 treatment sites in Uganda. Eligible patients had confirmed DR – TB, a treatment outcome in 2014–2019 and at least one of 15 pre-defined poor prognostic indicators at treatment initiation or during therapy. The pre-defined poor prognostic indicators were HIV co-infection, diabetes, heart failure, malignancy, psychiatric illness/symptoms, severe anaemia, alcohol use, cigarette smoking, low body mass index, elevated creatinine, hepatic dysfunction, hearing loss, resistance to fluoroquinolones and/or second-line aminoglycosides, previous exposure to second-line drugs (SLDs), and pregnancy. Tuberculosis treatment outcomes were treatment success, mortality, loss to follow up, and treatment failure as defined by the World Health Organisation. We used logistic and cox proportional hazards regression analysis to determine predictors of treatment success and mortality, respectively. Results: Of 1122 DR – TB patients, 709 (63.2%) were male and the median (interquartile range, IQR) age was 36.0 (28.0–45.0) years. A total of 925 (82.4%) had ≥2 poor prognostic indicators. Treatment success and mortality occurred among 806 (71.8%) and 207 (18.4%) patients whereas treatment loss-to-follow-up and failure were observed among 96 (8.6%) and 13 (1.2%) patients, respectively. Mild (OR: 0.57, 95% CI 0.39–0.84, p = 0.004), moderate (OR: 0.18, 95% CI 0.12–0.26, p

Objective: To assess adverse events (AEs) and efficacy of add-on cannabidiol (CBD) with a slower titration protocol in pediatric clinical practice. Methods: We conducted a prospective, open-label, multicenter study in seven French reference centers for rare epilepsies. Patients had slow titration to reach a target dose of 10 mg/kg/day within at least 1 month and then gradually increased to a maximum dose of 20 mg/kg/day. We analyzed AEs and efficacy at M1 (month 1), M2, and M6, comparing two sets of subgroups: Dravet syndrome (DS) vs. Lennox-Gastaut (LGS) and patients with clobazam (CLB+) vs. patients without (CLB−). Results: One hundred and twenty-five patients were enrolled (62 LGS, 48 DS, 5 Tuberous sclerosis, and 10 other etiologies). Median concomitant antiepileptic drugs (AEDs) was three (25th percentile: 3, 75th percentile: 4). Patients received a dose of 10 (10–12), 14 (10–20), and 15.5 mg/kg/day (10–20) at M1, M2, and M6, respectively. Twenty-six patients discontinued CBD, 19 due to lack of efficacy, 2 due to AEs, 4 for both, and 1 had a sudden unexpected death in epilepsy. AEs were reported in 61 patients (48.8%), mainly somnolence (n = 26), asthenia (n = 20), and behavior disorders (n = 16). Abnormal transaminases (≥3 times) were reported in 11 patients receiving both valproate and clobazam. AEs were significantly higher at M2 (p = 0.03) and increased with the number of AEDs (p = 0.03). At M6, total seizure frequency change from baseline was −41% ± 37.5% (mean ± standard deviation), and 28 patients (37.8%) had a reduction ≥50%. AE and efficacy did not differ between DS vs. LGS and CLB+ vs. CLB– patients. Significance: A slower titration of CBD dose delivered better tolerance with comparable efficacy to previous trials. Concomitant CLB did not increase efficacy rates but in a few cases increased AEs. This slow titration scheme should help guide clinicians prescribing CBD and allow patients to benefit from its potential efficacy.

Background Plasma proteins are known to interfere the drug metabolism during therapy. As limited information is available regarding the role of plasma proteins in HIV drug resistance during ART in HIV/AIDS patients, the present study aimed to identify and characterize the differentially expressed plasma proteins in the drug resistant and drug respondent groups of HIV-1 infected patients with > 6 years of first line ART. Methods Four-drug resistant (treatment failure) and four-drug respondent (treatment responder) patients were selected for plasma proteomic analysis based on viral load and drug resistance associated mutations from a cohort study designed on the first line ART patients who were enrolled in the antiretroviral therapy center, Sarojini Naidu Medical College, Agra, India from December 2009 to November 2016. After depleting high abundant proteins, plasma proteins were resolved using two-dimensional gel electrophoresis on IPG strips, pH range of 3–10. Spots were selected in the gel based on the density of staining which was common in the drug resistant and drug respondent groups separately. The fold change of each spot was calculated using image-J. Each protein spot was identified using the matrix assisted laser desorption/ionization-time of flight/time of flight (MALDI-TOF/TOF) after tryptic digestion. Peptide peaks were identified through flex analysis version 3.3, and a search against a protein data base using the internal Mascot. Gene ontology study was completed through STRING v.11 and Panther15.0. Results Out of eight spots from 2D gel samples analyzed by MALDITOF/TOF, two proteins were found to have significant score (> 56) after Flex analysis. These two proteins were identified to be apolipoprotein A1 and serotransferrin. The fold change expression of these two proteins were analyzed in drug resistant and drug respondent group. Apolipoprotein-A1 and serotransferrin were observed to be expressed 1.76 and 1.13-fold more respectively in drug respondent group compared to drug resistant group. The gene ontology analysis revealed the involvement of these two proteins in various important physiological processes. Conclusion Apolipoprotein A-I and serotransferrin were found to be expressed more in drug respondent group compared to drug resistant group.

Context A considerable number of patients affected by the overactive bladder syndrome (OAB) do not respond to pharmacotherapy and bladder training due to unsatisfactory response or intolerability. Objective To review the available literature assessing therapeutic effect of the available third-line treatment modalities for OAB. Evidence acquisition PubMed, Medline, and Cochrane databases were searched for all studies comparing outcomes of the available third-line treatment modalities for OAB. Evidence synthesis Several minimally invasive surgical procedures are available for patients with refractory OAB. These therapies include intravesical botulinum toxin type A, posterior tibial nerve stimulation, and sacral neuromodulation. Conclusions None of the mentioned therapeutic modalities shows strong superiority over another. If the results of one therapy are not satisfactory, switching to another third-line treatment can be attempted. The treatment algorithm is dependent on several factors, including age, comorbidity, patient preference, surgical expertise, and financial concerns. All these factors should be taken into consideration before initiation of treatment. Patient summary In the management of drug-resistant overactive bladder syndrome, the different minimally invasive treatments that are available are equal. If the results of one therapy are not satisfactory, switching to another treatment can be attempted. The treatment algorithm is dependent on several factors, including age, comorbidity, patient preference, surgical expertise, and financial concerns.

In cancer research, autophagy has been revealed as one of the major ways to maintain the metabolism of cancer cells, including glioma cells, through protein degradation. Meanwhile, autophagy is also regarded as a kind of mechanism to protect glioma cells from a harmful stimulus, such as chemical and radiation treatment. So, the inhibition of autophagy may be very helpful in curing glioma. This study aimed to determine the effect of autophagic inhibition on glioma cells using tubacin, a specific inhibitor of histone deacetylase 6(HDAC6). According to the results, tubacin inhibited the growth of both U251 and LN229 cells, which was accompanied by lower HDAC6 activity and accumulated autophagosome. The inhibition of HDCA6 also led to accumulation of autophagosome and death of glioma cells. Moreover, the combined treatment of tubacin and temozolomide, an alkylating agent used to treat glioblastoma, induced more severe glioma cell death. Thus, it can be concluded that inhibition of HDAC6 suppressed growth and drug resistance of glioma cells in-vitro through autophagic suppression and blocking of fusion of autophagosome and lysosome.

The present study was aimed to investigate the effect of intensity modulated radiotherapy (IMRT) followed by treatment with inhibitor for p38 MAPK, SB203580 on the rate of proliferation in drug resistant MCF-7 breast cancer cells. Interestingly, the results from immuno histochemistry and western blot assays revealed higher level of distribution of activated p38 MAPK in the drug resistant breast cancer tissues compared to the primary tissues. Treatment of the drug resistant MCF-7 cells with SB203580 led to a significant decrease in the phosphorylation of p38 MAPK. Exposure to IMRT caused a significant decrease in the rate of proliferation in drug resistant MCF-7breast cancer cells (P

// Yuan Wang 1 , Guo-Hui Wan 1 , Ying-Min Wu 1 , Hong-Sheng Wang 1 , Hai-Fang Wang 1 , Ge Zhang 1 , Lin-Lin Lu 1 , Zi-Qian Li 1 , Ka-Ying Chan 1 , Yan Zhou 1 , Shao-Hui Cai 2 , Yi-Fei Qi 1 and Jun Du 1 1 Department of Microbial and Biochemical Pharmacy, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China 2 Department of Pharmacology, School of Pharmaceutical Sciences, Jinan University, Guangzhou 510632, China Correspondence to: Jun Du, email: dujun@mail.sysu.edu.cn Keywords: drug resistant; HDAC inhibitor; JNJ26481585; AP-1; XIAP Received: June 21, 2017 Accepted: October 30, 2017 Epub: January 03, 2018 Published: March 06, 2018 ABSTRACT The underlying cause of treatment failure in many cancer patients is intrinsic and acquired resistance to chemotherapy. Recently, histone deacetylase (HDAC) inhibitors have developed into a promising cancer treatment. However, resistance mechanism induced by HDAC inhibitors remains largely unknown. Here we report that a HDAC inhibitor, JNJ-2648158 induced transcription of XIAP by activating AP-1 expression, which conferring resistance to chemotherapeutics. Our results showed that high expression of c-Fos caused by HDAC inhibitor promoted AP-1 formation during acquired resistance towards chemo-drugs, indicating an extremely poor clinical outcome in breast cancers and liver cancers. Our study reveals a novel regulatory mechanism towards chemo-drug resistance, and suggests that XIAP may serve as a potential therapeutic target in those chemo-resistant cancer cells.

The emergence of drug-resistant tuberculosis (DR-TB) has become a significant health problem in India. Delays in diagnosis and treatment initiation are frequently observed among patients with DR-TB, resulting in an increased risk of disease complications and high mortality and pretreatment lost to follow-up rates. To understand the factors associated with delays between the diagnosis and treatment, the study was carried out in Ahmedabad Municipal Corporation Area. A total of 177 DR-TB patients diagnosed in the year 2014 who had a delay in the initiation of treatment, and 23 initial defaulters were studied using a structured questionnaire. Fifty-four DOTS providers were also interviewed. Of 177 patients, 62.15% initiated treatment between 7 and 15 days and nearly 12% of them started the treatment after a month. The median duration of delay was 12 days (range: 8-144 days and interquartile range: 9-20 days). The most common reason for the delay in the initiation and initial default was the social and personal factors (48.80%), and in 34 (20%) of the patients, the delay was attributed to the effect of the previous treatment.

Background/Aim: To evaluate the effectiveness of enzalutamide in Italian patients with hormone-refractory metastatic castration-resistant prostate cancer, progressing after chemotherapy with docetaxel plus prednisone. Patients and Methods: A total of 60 patients were enrolled. Reduction in serum prostate-specific antigen (PSA) was assessed as the primary endpoint, while reduction in pain, safety, progression-free survival and overall survival represented secondary endpoints. Results: Enzalutamide was well tolerated, with a manageable toxicity profile and a modest objective response rate. A considerable difference in serum levels of PSA before and after treatment was observed. A significant correlation between PSA response and overall survival was also noted. The regression analysis revealed PSA level to be predictive of overall survival. Conclusion: Enzalutamide was shown to be an effective and welltolerated therapeutic option in patients with metastatic castration-resistant prostate cancer progressing after docetaxel plus prednisone treatment.

Objectives: The aim of this study was to estimate the prevalence and identify the risk factors for the development of drug-resistant Mycobacterium tuberculosis infection in a tertiary care center in Oman. Methods: We performed a cross-sectional review of culture-confirmed tuberculosis (TB) cases diagnosed at Sultan Qaboos University Hospital between August 2006 and March 2015. We compared drug-resistant TB cases with drug-sensitive cases to identify predictors of drug-resistant TB using univariate and multivariate logistic regression analysis. Results: Of the 260 TB cases reviewed, 73.1% were confirmed by culture. The proportion of multi-drug resistant TB was 1.8%. TB isolates resistant to any of the first-line TB drugs comprised (7.5%) of cases. Pyrazinamide monoresistance was the most frequently reported drug monoresistant pattern (3.5%). Previous treatment for TB (odds ratio (OR) 14.81; 95% CI 3.09−70.98, p < 0.001), female gender (OR 3.85; 95% Cl 1.07−13.90, p < 0.039), and younger age (OR 6.80; 95% Cl 1.61−28.75, p < 0.009) were found to be risk factors for development of first-line antituberculosis drug-resistant TB in multivariate analysis. Conclusions: Our results show that the rate of drug-resistant TB in our population is a public health issue of great concern. Previous treatment with antituberculosis drugs, female gender, and younger age are risk factors for the development of drug-resistant TB. These findings are useful adjuvants to guide clinicians and public health professionals in the early detection and appropriate treatment of cases of drug-resistant TB.

International audience; Epilepsy related to malformations of cortical development is frequently drug resistant or requires heavy medication, therefore surgery is key in their management. The role of stereotactic surgery has recently changed the diagnosis and treatment of focal cortical dysplasias (FCD), hypothalamic hamartomas (HH) and periventricular nodular heterotopias (PNH). In HH, radiosurgery using Gammaknife® leads to 60 % of seizure control and is associated with excellent neuropsychological results without significant endocrine function impairment. The seizure control rate is even higher (more than 80 %) with monopolar multiple stereotactic thermocoagulations and Laser interstitial Thermal Therapy (LiTT). While the first technique is associated with a 2 % complications rate (but with excellent neuropsychological outcomes), the latest has up to 22 % side effects in some series. All three of these techniques have encouraging results, but controlled studies are still lacking to provide evidence-based new therapeutic algorithms. With regard to the PNH, surgical management has long been limited by the depth of the lesions and their close anatomical relations with the functional brain connectome. Stereotactic approaches required to perform a SEEG, to locate the part of the PNH responsible for the seizure onset, are later followed by a stereotactic lesioning procedure, therefore doubling the bleeding risk. That is why SEEG-guided radiofrequency-thermocoagulation (SEEG guided-RF-TC), which makes it possible to perform these two steps in a single procedure, was considered as a promising option. A recent meta-analysis confirmed this intuition and reported 38 % of seizure-free patients and 81 % of responders with only 0.3 % of complications, making this approach the first treatment line, followed by LiTT. Among the multiple advances in the FCD identification by non-invasive investigations, a new modality of per-operative diagnostic procedure, the three-dimensional electrocorticography may lead to simplify the preoperative investigation and enhance the accuracy of FCD delineation. Evidence is nevertheless still insufficient to validate this promising concept. Conventional surgical resection has also been concerned by significant conceptual advances during the past few years, in particular with the development of the hodotopic approach, initially in oncologic surgery. Associated with a better understanding of neuroplasticity in epilepsy and the setting up of functional mapping during SEEG or during awake surgery, the possibility of surgical resections grew up. A short-term perspective in this field, when surgical resection remains impossible, would be to target crucial nodes of the epileptic network, distinct from the core functional connectome.

Long-term linezolid use is limited by mitochondrial toxicity-associated adverse events (AEs). Within a prospective, randomized controlled trial of linezolid to treat chronic extensively drug-resistant tuberculosis, we serially monitored the translational competence of mitochondria isolated from peripheral blood of participants by determining the cytochrome c oxidase/citrate synthase activity ratio. We compared this ratio with AEs associated with mitochondrial dysfunction. Linezolid trough concentrations were determined for 38 participants at both 600 mg and 300 mg doses. Those on 600 mg had a significantly higher risk of AE than those on 300 mg (HR 3·10, 95% CI 1·23–7 · 86). Mean mitochondrial function levels were significantly higher in patients before starting linezolid compared to their concentrations on 300 mg (P = 0·004) or 600 mg (P 2 μg/ml developing an AE related to mitochondrial toxicity, whether on 300 mg or 600 mg. Therapeutic drug monitoring may be useful to prevent the development of mitochondrial toxicity associated with long-term linezolid use., Highlights • Linezolid is increasingly being used to treat drug-resistant tuberculosis. • Long-term use of linezolid is limited by mitochondrial toxicity-associated adverse events. • We examined linezolid trough concentrations in chronic XDR-TB patients on linezolid. • Mitochondrial toxicity risk increased with increasing linezolid trough concentrations. • Therapeutic drug monitoring may help avoid mitochondrial toxicities in long-term linezolid treatment. Linezolid is increasingly being used to treat drug resistant tuberculosis, with the beneficial effect of linezolid tempered by the mitochondrial toxicity-associated adverse events seen with long-term use. Within a prospective, randomized controlled trial of linezolid for the treatment of chronic, extensively drug-resistant tuberculosis, we found that the risk of mitochondrial toxicity increased with increasing linezolid trough concentrations, with all patients with a mean trough > 2 μg/ml developing an adverse event related to mitochondrial toxicity. If our results are confirmed by other studies, therapeutic drug monitoring may become an important component of long-term linezolid treatment to prevent mitochondrial toxicity-related adverse events.

Supplemental Digital Content is available in the text, Antimicrobial peptides (AMPs) exhibit multiple activities against bacteria and fungi. A bovine myeloid antimicrobial peptide (BMAP-28) belongs to the cathelicidin-derived AMPs and has antimicrobial activity. Due to the rapidly increasing number of infections and outbreaks caused by pan-drug-resistant Acinetobacter baumannii (PDRAB), we sought to determine whether BMAP-28 and its 4 analog peptides (A837, A838, A839, and A840) have antimicrobial activity against PDRAB. Furthermore, we clarified the possible mechanism of inhibition by which of BMAP-28 acts against PDRAB. In the current study, we examined the inhibitory effect of BMAP-28 and its 4 analog peptides on the growth of PDRAB through minimal inhibitory concentration (MIC) analysis and short time killing assays. We also evaluated the effects of BMAP-28 and its analogs on the bacterial cell surface through the use of field emission scanning electron microscopy (FE-SEM). In order to determine the inhibitory mechanism of BMAP-28, we examined the interaction between BMAP-28 and outer membrane proteins (OMPs), especially the interaction between BMAP-28 and A. baumannii OmpA (AbOmpA), which is the main component of OMPs, by using a quartz crystal microbalance (QCM). BMAP-28 and its 4 analogs were effective in inhibiting the growth of PDRAB and had rapid killing ability. BMAP-28 showed exceptionally strong and rapid inhibitory effects on PDRAB when compared to the other peptides and was also shown to cause damage to the cell surface of PDRAB. Moreover, QCM analysis provided evidence of potential interaction between BMAP-28 and AbOmpA. These data indicate that BMAP-28 is a promising candidate for the treatment of PDRAB infections and that its inhibitory effects were related with its binding to AbOmpA.

Resistance to valproic acid (VPA), a first-line antiepileptic drug (AED), is occurring at an alarming rate, particularly in children. Signal nucleotide polymorphisms are considered crucial in this process. Therefore, we investigated whether the SCN1A polymorphism rs3812718 could be associated with VPA resistance. A total of 231 children with epilepsy who were solely administered VPA were enrolled. DNA was extracted from the peripheral blood samples and was genotyped by the Mass Array method. Furthermore, a meta-analysis was conducted between the drug responsive and resistant patients who were exposed to voltage-gated sodium channels. Results revealed that the TT genotype was associated with a higher risk of developing drug resistance (OR = 2.636, 95% CI 1.08–6.433, P = 0.033). After adjusting for the risk factors, a significant difference was still observed between the responsive and resistant groups (OR = 2.861, 95% CI 1.141–7.174, P = 0.025). Moreover, the recessive model was associated with a decreased drug resistance (OR = 0.402, 95% CI 0.167–0.968, P = 0.042) after correcting the risk factors. Meta-analysis of nine studies revealed similar results. In conclusion, our results proved that the rs3812718 TT genotype was associated with a high risk of developing drug resistance, and the recessive model could decrease the risk of VPA resistance.

Background: Patients with drug-resistant HIV often require complex antiretroviral regimens. However, combining fixed-dose combination tablets such as tenofovir–disoproxil–fumarate, emtricitabine, and cobicistat-boosted elvitegravir (TDF/FTC/EVG/cobi) with darunavir (DRV) can provide a simple, once-daily (QD), 2-tablet regimen for patients with drug-resistant HIV. Primary objective was to determine the percentage of patients with HIV-1 RNA Methods: We performed a retrospective chart review of patients initiated on TDF/FTC/EVG/cobi plus DRV. Results: Among the 21 included patients, prior resistance showed a median of 2 nucleoside reverse transcriptase inhibitor mutations, 1 nonnucleoside reverse transcriptase mutation, and 1 protease inhibitor mutation. At week 48, 14 (67%) patients achieved HIV-1 RNA Conclusion: According to this observational study, QD TDF/FTC/EVG/cobi plus DRV is considered safe, well tolerated, and generally effective in suppressing HIV drug-resistant virus.

SummaryBackgroundDrug-resistant epilepsy (DRE) is usually related to focal epilepsy (FE) and is present in up to 30% of patients. Several studies have found high rates of depressive symptoms and poor health related quality of life (HRQOL) in DRE patients but little information is available on these aspects for Spain.ObjectiveTo determine the prevalence of depressive symptoms in a cohort of Spanish patients with DRE and evaluate their HRQOL in comparison with patients with controlled FE (CFE).MethodsThis observational cross-sectional study analyzed FE patients, with and without DRE, recruited from different Spanish neurology outpatient clinics. Presence of depressive symptoms was assessed using the Montgomery–Asberg Depression Rating Scale (MADRS) and the Beck Depression Inventory-II (BDI-II). HRQOL was evaluated using the Quality of Life in Epilepsy Inventory (QOLIE-31).Results515 patients (DRE=248) were included. Mean (SD) age was 44.3 (15.4) years and 50.5% were male. Overall, 15.9% had a previous diagnosis of depressive symptoms (DRE=22.6%; CFE=9.7%, p

Potassium channels are the targets of antiepileptic drugs (AEDs), which play important roles in the etiology of epilepsy. KCNA1 and KCNA2 encode mammalian Kv1.1 and Kv1.2 channels, which are essential roles in the initiation and shaping of action potentials. KCNV2 encodes Kv8.2, which is a regional overlap with Kv2 subunits as functional heterotetramers. In our study, we aim to investigate whether variants of KCNA1, KCNA2, and KCNV2 genes influence susceptibility to genetic generalized epilepsies (GGEs) and the efficacy of AEDs. Seven hundred sixty-seven subjects (284 healthy controls, 279 drug-responsive, and 204 drug-resistant GGE patients) were enrolled in our study. Eight variants of KCNA1, KCNA2, and KCNV2 were assessed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry method. Results showed that there were no statistically significant correlations between the 8 variants of KCNA1, KCNA2, and KCNV2 and the risk/drug resistance of GGEs. In conclusion, our study suggests that KCNA1, KCNA2, and KCNV2 variants may not be involved in the risk/drug resistance of GGEs. Further multicenter, multiethnic, and large sample size pharmacogenetic and case–control studies are warranted to confirm our negative results.

Objective To examine demographic as well as clinical characteristics of the Carbapenam Resistant Enteriobacteriacae (CRE) Organisms cases in Houston, Texas, 2015-2016 Introduction According to CDC, CRE is used to describe bacteria that are non- susceptible to one or more carbapenems; doripenem, meropenem or imipenem and resistant to third generation cephalosporins like ceftriaxone, cefotaxime and ceftazidime. These organisms cause infections that are associated with high mortality rates and they have the potential to spread widely. Antibiotic resistant bacteria cause more than 2 million illnesses and at least 23,000 deaths each year in United States. CREs are found in many health care settings like acute care hospitals, long term care facilities, nursing homes, rehabilitation facilities and other health care settings. Although CREs includes a number of species, reporting in State of Texas is limited to CRE- Klebsiella species and CRE- E.coli . Methods Population-based surveillance data was generated from Houston’s electronic disease surveillance system reported to Houston Health Department (HHD) from October 2015 to July 2016. Descriptive analysis was performed to examine demographic and clinical characteristics across different age groups, gender and race/ethnicity. HHD has received a total of 463 CRE cases during the time period, out of which 72 were non-reportable and did not meet the case criteria, 187 were out of jurisdiction. The remaining 204 cases were included in this study. Results Out of a total of 204 cases, males and females were represented equally (50% each). The mean age of the cases was 67 years (age ranges from 22-98). Majority of the cases were in the older age group, 70 years and above 53 (26%), followed by 48 (24%) in age group 80 and above years. Among the different race/ethnic groups, African-Americans comprised of 82 (40%), followed by Whites 67 (33%) and Hispanics 33 (16%). Out of 204 cases, 156 (76%) were hospitalized, which included acute care hospital, long-term acute care or nursing home. Out of 156 hospitalized cases, 71 (34%) were in Intensive Care Unit (ICU) and 136 (67%) had an invasive or indwelling device. Of all the cases, 80% had CRE Klebsiella pneumoniae , followed by 11% who had CRE- E coli. The cases were distributed evenly across the city when plotted on ArcGIS with their residential addresses. Conclusions CRE cases are found to be more common among older age groups, African American population and in hospitalized patients. CRE can be a ground for increasing infectious diseases in the community and one of the reason may be unnecessary use of antimicrobial agents. This study provides a glimpse into the number of CRE cases reported in Houston since CREs are classified a separate disease in Texas. Further studies are needed to explore the occurrence of anti-microbial drug resistance among the specific population groups and how the case investigation efforts can be targeted to enhance prevention.

Background Gram-negative (G-ve) bacilli, particularly Pseudomonas aeruginosa and Acinetobacter baumannii , are important opportunistic multidrug-resistant (MDR) pathogens in hospitalized patients, contributing to their morbidity and mortality. These organisms may still keep their sensitivity to colistin and allowed its use for these selective therapeutic indications. Objectives The aim of the present study is to evaluate and compare the effectiveness and safety of both combined intravenous (i.v.) colistin with aerosolized colistin versus i.v. colistin alone in nosocomial pneumonia due to MDR G-ve pathogens in critically ill patients. Methods 40 Patients were hospitalized in ICU due to different etiologies. These patients experienced nosocomial pneumonia. The pathogenic organisms were G-ve MDR bacilli and only susceptible to colistin. The first group received both i.v. colistin with aerosolized colistin versus (vs.) the second group who received i.v. colistin alone. Results Mortality was less in patients who received i.v. plus inhaled colistin. Conclusion Colistin is a reasonable safe last-line therapeutic alternative for pneumonia due to MDR G-ve pathogens. Aerosolized colistin may be considered as a useful adjunctive to i.v. colistin.

SummaryObjective To investigate the effect of cathodal transcranial direct-current stimulation (c-tDCS) on seizure frequency in patients with drug-resistant temporal lobe epilepsy (TLE). Method Twenty-nine patients with drug-resistant TLE participated in this study. They were randomized to experimental or sham group. Twenty participants (experimental group) received within-session repeated c-tDCS intervention over the affected temporal lobe, and nine (sham group) received sham tDCS. Paired-pulse transcranial magnetic stimulation was used to assess short interval intracortical inhibition (SICI) in primary motor cortex ipsilateral to the affected temporal lobe. SICI was measured from motor evoked potentials recorded from the contralateral first dorsal interosseous muscle. Adverse effects were monitored during and after each intervention in both groups. A seizure diary was given to each participant to complete for 4 weeks following the tDCS intervention. The mean response ratio was calculated from their seizure rates before and after the tDCS intervention. Results The experimental group showed a significant increase in SICI compared to the sham group (F = 10.3, p = 0.005). None of the participants reported side effects of moderate or severe degree. The mean response ratio in seizure frequency was −42.14% (standard deviation [SD] 35.93) for the experimental group and −16.98% (SD 52.41) for the sham group. Significance Results from this pilot study suggest that tDCS may be a safe and efficacious nonpharmacologic intervention for patients with drug-resistant TLE. Further evaluation in larger double-blind randomized controlled trials is warranted.

AimsTo review and assess the definitions of drug resistance and the evidence supporting treatment for drug resistant overactive bladder/detrusor overactivity (OAB/DO).MethodsEvidence review of the extant literature and consensus of opinion was used to derive the summary recommendations.ResultsDrug resistance or drug refractory status has been inconsistently defined and reported in current evident sources. Recent publications use some correlation of lack of efficacy and or experienced side effects to define drug resistance. Algorithms based upon these definitions largely relate to the appropriate use of neuromodulation or botulinum neurotoxin, based upon patient selection and patient choice. Current treatment pathways are hampered by inability to consistently profile patients to optimize management, particularly after failure of initial pragmatic treatment.ConclusionsFurther research is recommended to better identify patient phenotype for purposes of directing optimized therapy for OAB/DO. Current treatment algorithms are influenced by extensive data generated from recent neuromodulation and botulinum neurotoxin trials.

Background With various changes implemented such as perioperative antibiotics for tangential excision, this retrospective study reviews the infection profile of burn patients at Singapore’s only centralized burns unit. Worldwide, the appearance of multidrug-resistant (MDR) strains of Acinetobacter baumannii (A. baumannii) continues to worsen patient outcomes. This study also surveys the role of blood cultures in burns at our unit. Methods Four hundred fifty-two burn patients admitted to the unit between 2011 and 2013, and with cultures performed, were included in the study. The yields of various cultures were evaluated and 2684 samples were amassed, of which 984 (36.7 %) were positive. Patient variables for predictors of MDR A. baumannii infection acquisition and bacteremia were evaluated through multivariate analyses. Results Pseuodomonas aeruginosa (P. aeruginosa) (67 patients) was the most common organism in those with total body surface area (TBSA) burn Conclusions MDR A. baumannii infection burdens patient management, especially in those with TBSA burn ≥20 % and longer hospital stay. Prophylactic antibiotics may reduce perioperative bacteremia, but their role in MDR infections needs to be evaluated. The role of blood cultures in TBSA burn

Tuberculosis (TB) remains the major health problem causing morbidity and mortality throughout the world. Increase in multidrug resistant, extensively drug-resistant, and totally drug-resistant cases of tuberculosis are causing concern to the health administrators of TB control programs. In spite of tremendous research on drug targets and drugs in TB, no new drug which is safer and more effective, has come out. This mini-review focuses on different important drug targets in Mycobacterium tuberculosis reported and emphasizes the urgency for new drug development and integrative approach for successful control of TB.

& Aims: We describe our experience with botulinum- A toxin (BTX-A) in children presenting idiopathic overactive bladder (OAB) refractory to anticholinergic drugs. Material and Methods: 21 patients, aged 8 – 12 years, were treated over a 3-year period. BTX-A was administered at a dosage of 12.5 UI / kg body weight, without exceeding 200 UI, at 20 detrusor sites. To ensure a stable solution, each 100 UI of botulinum toxin was diluted with 5 cc saline solution just prior to performing the cystoscopy. Results: No patient presented with severe systemic complications or urinary retention after injection therapy; 6 patients presented with slight hematuria for 2 – 3 days. The clinical results were as follows. At 6 months, 8 / 21 patients (38 % ) showed full response, 12 / 21 (57 % ) had a partial response after a 2 nd injection, and 1 / 21 (4.7 % ) showed no response after a 2 nd injection. At 12 months, 16 patients (76 % ) had a full response, 4 (19 % ) showed a partial response after a 3 rd injection, and 1 patient (4.7 % ) still had no response. At 18 months, 18 patients (85 % ) showed a full response, 2 patients (9.5 % ) had a partial response, 1 patient (4.7 % ) had no response. At the end of this study, 8 / 21 patients (38 % ) were symptomfree, after only one botulinum detrusor injection, 13 / 21 patients (61.9 % ) received a second botulinum injection because of recurrence of urinary incontinence 6 – 7 months after the initial treatment, and 4 / 21 patients (19 % ) received a third injection 12 – 14 months after the initial treatment, of whom 2 had a full response and 2 had a partial response. Patient no. 20 refused any further botulinum treatment after the 2 nd unsuccessful injection series. Conclusion: Intravesical BTX-A injection appears to be safe and useful in children presenting with idiopathic overactive drug-resistant bladder.

Background and objective : There are no recent data on the prevalence of drug-resistant tuberculosis (DR TB) in Cambodia. We aim to describe TB drug resistance amongst adults with pulmonary and extra-pulmonary TB and human immunodeficiency virus (HIV) co-infection in a national referral hospital in Phnom Penh, Cambodia. Design : Between 22 November 2007 and 30 November 2009, clinical specimens from HIV-infected patients suspected of having TB underwent routine microscopy, Mycobacterium tuberculosis culture, and drug susceptibility testing. Laboratory and clinical data were collected for patients with positive M. tuberculosis cultures. Results : M. tuberculosis was cultured from 236 HIV-infected patients. Resistance to any first-line TB drug occurred in 34.7% of patients; 8.1% had multidrug resistant tuberculosis (MDR TB). The proportion of MDR TB amongst new patients and previously treated patients was 3.7 and 28.9%, respectively ( p

To the Editor: Since the initiation of multidrug therapy for leprosy (Hansen disease) in the 1980s by using rifampin, dapsone, and clofazimine, resistance to rifampin and dapsone has been observed worldwide and is still prevalent (1,2). Because few alternative effective antileprosy drugs exist, resistance to these first-line drugs could seriously affect leprosy control programs. We report a documented case of primary multidrug-resistant (MDR) leprosy in the United States. A man from American Samoa migrated to Hawaii at age 25 years and, at age 41 years, first sought care for generalized erythematous papules and plaques. A skin biopsy showed borderline lepromatous (BL) leprosy (Figure, panel A). He had no prior history of leprosy and no prior treatment. He was treated for 44 months with a daily regimen of dapsone (100 mg), clofazimine (100 mg), and rifampin (600 mg). He appeared to comply with this regimen, and the lesions slowly resolved. He remained free of any new lesions until 4 years after completing treatment, when multiple brown hyperpigmented patches appeared on his lower legs. A skin biopsy showed only hemosiderin deposition but no organisms. Figure Acid-fast organisms from biopsy specimens of a man with leprosy, United States. Fite-stained sections show numerous acid-fast bacilli in the initial skin biopsy specimen (A) and in the biopsy specimen taken at relapse, 6 years after completion of treatment ... At 51 years of age, 6 years after completing treatment, the man again sought care for a 2-week history of multiple generalized erythematous papules and plaques on his face, trunk, and extremities. Some lesions were pruritic but nontender. A skin biopsy showed chronic inflammatory infiltrates with numerous acid-fast bacilli (Figure, panel B). Clinically considered to have relapsed BL leprosy, he was again treated daily with dapsone (100 mg), clofazimine (50 mg), and rifampin (600 mg). After 1 month of this regimen, no clinical improvement was observed. Real-time PCR using the Mycobacterium leprae–specific repetitive element assay (3) confirmed the presence of M. leprae in biopsy specimens taken at the initial diagnosis and at relapse. Molecular genotyping of these samples with a panel of single-nucleotide polymorphism (SNP) and variable number of tandem repeat (VNTR) markers (4) showed that both biopsy specimens harbored M. leprae with the identical SNP subtype 3I and VNTR profile. PCR/DNA sequencing of the drug resistance–determining regions of M. leprae from these samples showed mutations within codon 53 of the folP1 gene (ACC→GCC) and in codon 425 of the rpoB gene (TCG→TTG). These mutations have been characterized to induce high-level resistance to dapsone and rifampin, respectively (5,6). Careful evaluation of electropherograms of these drug resistance–determining regions showed only the resistant alleles in both strains. These data indicated that this patient had been infected with MDR M. leprae before his initial treatment for leprosy. Therefore, when he was initially treated with leprosy multidrug therapy, he was essentially given clofazimine monotherapy. This treatment appears to have resulted in a slow, temporary clinical improvement. After relapse, he was placed on a daily regimen of clofazimine (100 mg), clarithromycin XL (500 mg), and minocycline (100 mg). The lesions clinically improved within 2 weeks, and the patient no longer noted any pruritus or tenderness in the lesions. This report documents a case of primary MDR leprosy in the United States. In evaluating several previous biopsy samples from other patients in Hawaii, we have not seen any rifampin-resistant or MDR isolates. Health officials in American Samoa, the patient’s country of origin, indicated that they were not aware of drug-resistant M. leprae among their patients (D. Scollard, pers. comm.). The patient reported no family history of leprosy, and no other contact could be identified. The origin of the MDR M. leprae in this case cannot be definitively determined. Drug-resistant leprosy, including dapsone- and rifampin-resistant and MDR leprosy, has been reported in other parts of the world, usually in association with relapse after insufficient therapy (1,2). Relapses in leprosy are not usually seen until many years after completion of treatment (7,8). In the United States, among patients treated for 2 years with a multidrug protocol involving daily rifampin, no relapses were observed after 10–15 years’ follow-up (9). Most new or worsening skin lesions clinically suspected to be relapses are actually leprosy reactions (10), which affect 30%–50% of patients. In the patient reported here, leprosy relapsed with MDR M. leprae 6 years after completion of treatment. The emergence of drug resistance poses a serious threat to leprosy control programs that rely on a secondary intervention, such as chemotherapy, because a leprosy vaccine is not available. Clinicians should be aware that persons who have acquired leprosy in other countries could have infection resulting from drug-resistant M. leprae. When resistance is suspected, biopsy samples should be analyzed by using molecular assays that enable rapid identification of mutations associated with drug resistance directly from paraffin-embedded biopsy specimens. For patients in the United States, this analysis is available through the National Hansen’s Disease (Leprosy) Program (www.hrsa.gov/hansensdisease/diagnosis/index.html), and for US patients, the program provides the 3-drug regimen for leprosy free of charge. When needed, minocycline, clarithromycin, and ofloxacin are provided as alternatives to treat leprosy.

A 60-year-old female came to our hospital with defective vision due to persistent diabetic macular edema and was treated with intravitreal ozurdex implant in the right eye. Three days later, the patient presented with diminution of vision, ocular pain, congestion, and hypopyon with no fundus view. B-scan ultrasonography showed vitritis, and diagnosis of endophthalmitis was made. Subsequently, 25-gauge pars plana vitrectomy was performed along with intravitreal vancomycin and amikacin and removal of implant. On culture, there was growth of coagulase-negative staphylococcus which was resistant to ofloxacin antibiotic. A week following treatment, there was significant improvement in the patient's sign and symptoms with improvement in vision. Our case demonstrated that acute endophthalmitis can occur following dexamethasone intravitreal implant.

Free-flying turkey vultures (Cathartes aura) were sampled in California to investigate the fecal shedding prevalence and antimicrobial susceptibility of Salmonella enterica, Campylobacter spp., and Escherichia coli. Nine different serotypes of Salmonella enterica were detected in cloacal swabs from turkey vultures, and 6% of vultures were shedding Campylobacter spp.. Turkey vultures sampled at a location with range sheep were more likely to shed tetracycline-resistant E. coli, suggesting that proximity to livestock facilities could facilitate acquisition of drug-resistant bacteria in avian scavengers. These findings illustrate the importance of assessing BRIEF COMMUNICATION Global trends in conversion of wild lands to agriculture have been associated with shifts in food resources for avian scavengers, with an increased dependence of some populations on domestic animal carrion and farm refuse. 9 Regular consumption of livestock remains places scaveng- ing birds at heightened risk of exposure to veterinary drug residues, as evidenced by vulture die-offs from diclofenac toxicity on the Indian subcontinent. 9 A Canadian study found that wildlife residing near livestock operations exhib- ited greater antimicrobial resistance relative to other habitats. 2 Given these findings, and the problem of drug resistance in the agricultural industry, 8

Tuberculosis (TB) is responsible for 1.4 million deaths annually. Wide-spread misuse of anti-tubercular drugs over three decades has resulted in emergence of drug resistant TB including multidrug-resistant TB and extensively drug-resistant TB globally. Accurate and rapid diagnosis of drug-resistant TB is one of the paramount importance for instituting appropriate clinical management and infection control measures. The present article provides an overview of the various diagnostic options available for drug resistant TB, by searching PubMed for recent articles. Rapid phenotypic tests still requires days to weeks to obtain final results, requiring biosafety and quality control measures. For newly developed molecular methods, infrastructure, training and quality assurance should be followed. Successful control of drug resistant TB globally will depend upon strengthening TB control programs, wider access to rapid diagnosis and provision of effective treatment. Therefore, political and fund provider commitment is essential to curb the spread of drug resistant TB.

Background : Drug-resistant tuberculosis is an important issue for public health. There is a rise in the trend of drug-resistant tuberculosis, especially multi drug resistance (MDR), in different parts of world, India being one of the high burden countries. This study is undertaken to assess the various patterns of resistance among confirmed drug resistant pulmonary tubercular patients and to initiate second line anti tubercular treatment. Aims and Objectives : To assess various resistance patterns among confirmed drug resistant pulmonary tubercular patients and for the initiation of appropriate drug regimens in our setup. Study Design : An observational prospective study. Materials and Methods : This study was conducted at Rajiv Gandhi Institute of Chest Diseases, Bangalore between January 2005 and November 2010. A total of 309 drug resistant tuberculosis cases were studied. Sputum culture and drug sensitivity were carried out at National Tuberculosis Institute. Drug sensitivity testing done for all first line drugs, except pyrazinamide, by using LJ media. Results : In this study, out of 309 patients, MDR pattern was observed in 224 (72%), of which 20 (6.47%) had resistance only to isoniazid (INH) and rifampicin (RMP), 58 (18.7%) had resistance to INH, RMP, and either of the other first line drugs streptomycinor ethambutol and 146 (47.25%) had resistance to all first line drugs. Poly drug resistance pattern was observed in 72 (23.3%) and Mono drug resistance in 13 (4.2%). Conclusion : In the present study the most common pattern observed is MDR with predominant resistance to INH. There is a rise in the number of drug resistant tuberculosis cases, especially MDR. Hence close monitoring of drug resistant pattern is required to formulate designs of different regimens in the treatment of drug resistant tuberculosis; especially MDR-TB based on accredited laboratory reports, in a specialized center which is very much essential for the betterment of the patients and the community.

Recent case reports describe multidrug-resistant influenza A pandemic (H1N1) 2009 virus infection in immunocompromised patients exposed to neuraminidase inhibitors because of an I223R neuraminidase mutation. We report a case of multidrug-resistant pandemic (H1N1) 2009 bearing the I223R mutation in an ambulatory child with no previous exposure to neuraminidase inhibitors.

Cancer stem cells (CSCs) are cells within a tumor that possess the capacity to self-renew and maintain tumor-initiating capacity through differentiation into the heterogeneous lineages of cancer cells that comprise the whole tumor. These tumor-initiating cells could provide a resource for cells that cause tumor recurrence after therapy. Although the cell origin of CSCs remains to be fully elucidated, mounting evidence has demonstrated that Epithelial-to-Mesenchymal Transition (EMT), induced by different factors, is associated with tumor aggressiveness and metastasis and these cells share molecular characteristics with CSCs, and thus are often called cancer stem-like cells or tumor-initiating cells. The acquisition of an EMT phenotype is a critical process for switching early stage carcinomas into invasive malignancies, which is often associated with the loss of epithelial differentiation and gain of mesenchymal phenotype. Recent studies have demonstrated that EMT plays a critical role not only in tumor metastasis but also in tumor recurrence and that it is tightly linked with the biology of cancer stem-like cells or cancer-initiating cells. Here we will succinctly summarize the state-of-our-knowledge regarding the molecular similarities between cancer stem-like cells or CSCs and EMT-phenotypic cells that are associated with tumor aggressiveness focusing on solid tumors.

Summary Purpose: We characterized a family with autosomal dominant lateral temporal epilepsy (ADLTE) whose proband presented uncommon electroclinical findings such as drug-resistant seizures and recurrent episodes of status epilepticus with dysphasic features. Methods: The electroclinical characteristics and LGI1 genotype were defined in the family. In the proband, the ictal pattern was documented during video-EEG monitoring and epileptic activity was mapped by EEG/fMRI. Results: The affected members who were studied had drug-resistant seizures. In the proband, seizures with predominant dysphasic features often occurred as partial status epilepticus. The video-EEG-documented ictal activity and fMRI activation clearly indicated the elective involvement of the left posterior lateral temporal cortex. Sequencing of LGI1 exons revealed a heterozygous c.367G>A mutation in exon 4, resulting in a Glu123Lys substitution in the protein sequence. Conclusions: The uncommon clinical pattern (high seizure frequency, drug-resistance) highlights the variability of the ADLTE phenotype and extends our knowledge of the clinical spectrum associated with LGI1 mutations.

Summary Introduction Epilepsy associated with tuberous sclerosis complex (TSC) is drug resistant in more than half of the patients. Epilepsy surgery may be an alternative treatment option, if the epileptogenic tuber can be identified reliably and if seizure reduction is not at the expense of cognitive or other functions. We report the pre-surgical identification of the epileptogenic tuber and post-surgical outcome of patients with TSC in The Netherlands. Methods Twenty-five patients underwent the pre-surgical evaluation of the Dutch Comprehensive Epilepsy Surgery Programme, including a detailed seizure history, interictal and ictal video EEG registrations, 3D FLAIR MRI scans and neuropsychological testing. Suitability of the candidates was decided in consensus. Seizure outcome, scored with the Engel classification, and cognition were reassessed at fixed post-surgery intervals. Results Epilepsy surgery was performed in six patients. At follow-up, four patients had Engel classification 1, two had classification 4. Improved development and behaviour was perceived by the parents of two patients. Epilepsy surgery was not performed in 19 patients because seizures were not captured, ictal onset zones could not be localised or were multiple, interictal EEG, video EEG and MEG results were not concordant, or seizure burden had diminished during decision making. A higher cognition index was found in the surgical patients compared to the non-surgical candidates. Conclusions Epilepsy surgery can be performed safely and successfully in patients in whom semiology, interictal EEG, ictal EEG, MEG and the location of tubers are concordant. In other cases the risk of surgery should be weighed against the chance of seizure relief and in case of children subsequent impact on neurodevelopment.

Purpose Epilepsy patients have a significantly higher rate of anxiety and depression than the general population, and psychiatric disease is particularly prevalent among drug resistant epilepsy patients. Symptoms of anxiety and depression might serve as a barrier to appropriate epilepsy care. The aim of this study was to determine if drug resistant epilepsy patients with symptoms of anxiety and/or depression receive different epilepsy management than controls. Method We identified 83 patients with drug resistant focal epilepsy seen at the Penn Epilepsy Center. Upon enrollment, all patients completed 3 self-report scales and a neuropsychiatric inventory and were grouped into those with symptoms of anxiety and/or depression and controls. Each patient's medical records were retrospectively reviewed for 1–2 years, and objective measures of outpatient and inpatient epilepsy management were assessed. Results At baseline, 53% ( n =43) of patients screened positive for symptoms of anxiety and/or depression. The remaining 47% ( n =38) served as controls. Patients with anxiety and/or depression symptoms had more missed outpatient visits per year compared to controls (median 0.84 vs. 0.48, p =0.02). Patients with symptoms of both anxiety and depression were more likely to undergo an inpatient admission or procedure (56% vs. 24%, p =0.02). Conclusion For most measures of epilepsy management, symptoms of anxiety and/or depression do not alter epilepsy care; however, drug resistant epilepsy patients with anxiety and/or depression symptoms may be more likely to miss outpatient appointments, and those with the highest burden of psychiatric symptoms may be admitted more frequently for inpatient services compared to controls.