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Background and Aims: Paravertebral block (PVB) is the regional anaesthesia of choice for percutaneous nephrolithotomy (PCNL). Erector spinae plane block (ESPB) is also effective for the same. This study aims to compare the analgesic efficacy and ease of performing PVB or ESPB for PCNL surgery., Methods: This study was conducted in 60 patients undergoing PCNL, who were randomised to Group P ( n = 30; received ultrasound-guided [USG] PVB) and Group E ( n = 30; received USG ESPB) after general anaesthesia. Blocks were administered at T10 level on the side of the surgery using 20 ml of 0.25% bupivacaine. The trachea was extubated at the end of surgery. The primary outcome was analgesia duration, and secondary outcomes were postoperative pain scores, analgesic consumption, ease of block performance, time taken to perform the block and complications between the two groups. Continuous variables were compared using an independent sample t -test, and categorical variables were analysed using Pearson's Chi-square test., Results: Demographic variables were comparable in both groups. The mean (standard deviation [SD]) time of first rescue analgesia in Group P and Group E were 16.6 (20.4)(95% confidence interval [CI]: 9.02-20.32) h and 16.3 (21.8) (95% CI: 8.17-24.51) h, respectively ( P = 0.95). The postoperative pain scores and number of doses of analgesics used were comparable between the groups ( P > 0.05). The time taken to perform PVB was much longer compared to the time taken to perform ESPB ( P = 0.01)., Conclusion: USG PVB and ESPB were equally effective for postoperative analgesia for PCNL surgery., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Indian Journal of Anaesthesia.)

Background: Regulatory T cell (Treg) therapy is considered an alternative approach to induce tolerance in transplantation. If successful, this therapy may have implications on immunosuppression minimization/withdrawal to reduce drug-induced toxicity in patients. The aim of this study was to assess the efficacy of the mTORC1/C2 inhibitor, AZD8055, in the manufacturing of clinically competent Treg cells and compare the effects with those induced by rapamycin (RAPA), another mTOR inhibitor commonly used in Treg expansion protocols., Methods: Primary human Treg cells were isolated from leukapheresis product. Cell viability, expansion rates, suppressive function, autophagy, mitochondrial unfolded protein response (mitoUPR), and cell metabolic profile were assessed., Results: We observed a stronger inhibition of the mTORC2 signaling pathway and downstream events triggered by Interleukin 2 (IL2)-receptor in AZD8055-treated cells compared with those treated with RAPA. AZD8055 induced progressive metabolic changes in mitochondrial respiration and glycolytic pathways that disrupted the long-term expansion and suppressive function of Tregs. Unlike RAPA, AZD8055 treatment impaired autophagy and enhanced the mitoUPR cell stress response pathway., Conclusions: A distinct pattern of mTOR inhibition by AZD, compared with RAPA, induced mitochondrial stress response and dysfunction, impaired autophagy, and disrupted cellular bioenergetics, resulting in the loss of proliferative potential and suppressive function of Treg cells.

Background: Development of valid and feasible quality indicators (QIs) is needed to track quality initiatives for osteoarthritis pain management in primary care settings., Methods: Literature search identified published guidelines that were reviewed for QI extraction. A panel of 14 experts was assembled, including primary care physicians, rheumatologists, orthopedic surgeons, pain specialists, and outcomes research pharmacists. A screening survey excluded QIs that cannot be reliably extracted from the electronic health record or that are irrelevant for osteoarthritis in primary care settings. A validity screening survey used a 9-point Likert scale to rate the validity of each QI based on predefined criteria. During expert panel discussions, stakeholders revised QI wording, added new QIs, and voted to include or exclude each QI. A priority survey used a 9-point Likert scale to prioritize the included QIs., Results: Literature search identified 520 references published from January 2015 to March 2021 and 4 additional guidelines from professional/governmental websites. The study included 41 guidelines. Extraction of 741 recommendations yielded 115 candidate QIs. Feasibility screening excluded 28 QIs. Validity screening and expert panel discussion excluded 73 QIs and added 1 QI. The final set of 15 prioritized QIs focused on pain management safety, education, weight-management, psychological wellbeing, optimizing first-line medications, referral, and imaging., Conclusion: This multi-disciplinary expert panel established consensus on QIs for osteoarthritis pain management in primary care settings by combining scientific evidence with expert opinion. The resulting list of 15 prioritized, valid, and feasible QIs can be used to track quality initiatives for osteoarthritis pain management., (© 2023. The Author(s).)

While there is an evolving literature on the benefits of texting and patient-centered technologies, texting initiatives have not focused on family members. We sought to identify patients' family members' perspectives on facilitators and barriers to using 1 digital texting innovation to promote family-centered care during patients' hospitalizations. This qualitative study was conducted at a tertiary care center in Houston, consisting of 7 hospitals (1 academic hospital and 6 community hospitals), involving analyzation of 3137 comments from family members who used the digital texting technology. Thematic analysis methods were used. The data analysis for loved ones' feedback resulted in 4 themes as facilitators: (1) inpatient text messaging keeps loved ones updated and connected (n = 611); (2) inpatient text messaging allows for stronger continuity of communication (n = 69); (3) messaging promotes a sense of staff compassion and service (n = 245); and (4) messaging reduces phone calls (n = 65). The data analysis resulted in 4 themes as barriers to text messaging helpfulness: (1) messages could feel generic (n = 31); (2) inpatient texting was not needed if all loved ones were regularly at bedside (n = 6); (3) messages could have a perceived delay (n = 37); and (4) security features could impact convenience (n = 29). Our findings indicate that family members and loved ones value inpatient text messages, not only for the information the messages provide, but also because the act of writing text messages and preparing loved ones shows inclusiveness, compassion, and family-centered care., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

For decades, the remote island nation of Samoa (population ~200,000) has faced endemic typhoid fever despite improvements in water quality, sanitation, and economic development. We recently described the epidemiology of typhoid fever in Samoa from 2008 to 2019 by person, place, and time; however, the local Salmonella enterica serovar Typhi (S. Typhi) population structure, evolutionary origins, and genomic features remained unknown. Herein, we report whole genome sequence analyses of 306 S. Typhi isolates from Samoa collected between 1983 and 2020. Phylogenetics revealed a dominant population of rare genotypes 3.5.4 and 3.5.3, together comprising 292/306 (95.4%) of Samoan versus 2/4934 (0.04%) global S. Typhi isolates. Three distinct 3.5.4 genomic sublineages were identified, and their defining polymorphisms were determined. These dominant Samoan genotypes, which likely emerged in the 1970s, share ancestry with other 3.5 clade isolates from South America, Southeast Asia, and Oceania. Additionally, a 106-kb pHCM2 phenotypically cryptic plasmid, detected in a 1992 Samoan S. Typhi isolate, was identified in 106/306 (34.6%) of Samoan isolates; this is more than double the observed proportion of pHCM2-containing isolates in the global collection. In stark contrast with global S. Typhi trends, resistance-conferring polymorphisms were detected in only 15/306 (4.9%) of Samoan S. Typhi, indicating overwhelming susceptibility to antibiotics that are no longer effective in most of South and Southeast Asia. This country-level genomic framework can help local health authorities in their ongoing typhoid surveillance and control efforts, as well as fill a critical knowledge gap in S. Typhi genomic data from Oceania. IMPORTANCE In this study, we used whole genome sequencing and comparative genomics analyses to characterize the population structure, evolutionary origins, and genomic features of S. Typhi associated with decades of endemic typhoid fever in Samoa. Our analyses of Samoan isolates from 1983 to 2020 identified a rare S. Typhi population in Samoa that likely emerged around the early 1970s and evolved into sublineages that are presently dominant. The dominance of these endemic genotypes in Samoa is not readily explained by genomic content or widespread acquisition of antimicrobial resistance. These data establish the necessary framework for future genomic surveillance of S. Typhi in Samoa for public health benefit.

Salmonella enterica serovar Typhi (S. Typhi) is either widely distributed or proximally transmitted via fecally-contaminated food or water to cause typhoid fever. In Samoa, where endemic typhoid fever has persisted over decades despite water quality and sanitation improvements, the local patterns of S. Typhi circulation remain unclear. From April 2018-June 2020, epidemiologic data and GPS coordinates were collected during household investigations of 260 acute cases of typhoid fever, and 27 asymptomatic shedders of S. Typhi were detected among household contacts. Spatial and temporal distributions of cases were examined using Average Nearest Neighbor and space-time hotspot analyses. In rural regions, infections occurred in sporadic, focal clusters contrasting with persistent, less clustered cases in the Apia Urban Area. Restrictions to population movement during nationwide lockdowns in 2019-2020 were associated with marked reductions of cases. Phylogenetic analyses of isolates with whole genome sequences (n = 186) revealed one dominant genotype 3.5.4 (n = 181/186) that contains three Samoa-exclusive sub-lineages: 3.5.4.1, 3.5.4.2, and 3.5.4.3. Variables of patient sex, age, and geographic region were examined by phylogenetic groupings, and significant differences (p<0.05) associated genetically-similar isolates in urban areas with working ages (20-49 year olds), and in rural areas with age groups typically at home (<5, 50+). Isolates from asymptomatic shedders were among all three sub-lineages. Whole genome sequencing provided evidence of bacterial genetic similarity, which corroborated 10/12 putative epidemiologic linkages among cases and asymptomatic shedders, as well as 3/3 repeat positives (presumed relapses), with a median of one single nucleotide polymorphism difference. These findings highlight various patterns of typhoid transmission in Samoa that differ between urban and rural regions as well as genomic subtypes. Asymptomatic shedders, detectable only through household investigations, are likely an important reservoir and mobile agent of infection. This study advances a "Samoan S. Typhi framework" that supports current and future typhoid surveillance and control efforts in Samoa., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: M.M.L. has a patent entitled “Broad spectrum vaccine against typhoidal and nontyphoidal Salmonella disease” (US 9,011,871 B2) issued. R.M.R.-B. reports non-financial support from the Government of Samoa during the conduct of the study.

Background and Aims: The internal jugular vein (IJV) is the most common site for central venous cannulation. Ultrasonography (USG)-guided brachiocephalic vein (BCV) cannulation has been described recently. The objective of this study was to compare the first attempt success rate, overall success rate and procedural ease between two techniques., Methods: This was a prospective, single-blinded, randomised clinical study. Patients were randomly allocated into two groups using computer generated random table. Group IJV included 55 patients of USG-guided out-of-plane approach to the right IJV cannulation and group BCV included 55 patients for USG-guided supraclavicular in-plane approach to right BCV cannulation. The success rate, number of redirections needed, vein and needle tip visualisation, cannulation time and complication rate were compared between the groups., Results: Demographic parameters were similar between the groups. Success rate of cannulation was 98.5% in IJV group and 100% in group BCV (P = 0.31). The first attempt success rate was 76.3% and 81.81% in IJV and BCV group, respectively (P = 0.42). IJV was collapsed in 14.5% cases and BCV was collapsed in 0.9% cases. The needle visualisation was better in BCV group (94.54%) compared to IJV (80%) (P = 0.02) group, which was statistically significant. The numbers of redirections of needle were more in IJV group. Thus the procedural ease was better with BCV than IJV., Conclusion: Supraclavicular USG-guided in-plane BCV cannulation is a good alternative to USG-guided out-of-plane IJV cannulation, because of good calibre of the vein and better needle visualisation in the BCV group., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Indian Journal of Anaesthesia.)

Background: There is a scarcity of data comparing the consequences of first and second COVID-19 waves on kidney transplant recipients (KTRs) in India., Methods: We conducted a single-centre retrospective study of 259 KTRs with COVID-19 to compare first wave (March 15-December 31 2020, n = 157) and second wave (April 1-May 31 2021, n = 102)., Results: KTRs during second wave were younger (43 vs. 40 years; p-value .04) and also included paediatric patients (0 vs. 5.9%; p-value .003). Symptoms were milder during the second wave (45 vs. 62.7%; p-value .007); COVID-19 positive patients had less frequent cough (32 vs. 13.8%; p-value .001), fever was less frequent (58 vs. 37%; p-value .001), and we observed fewer co-morbidities (11 vs. 20.6%; p-value .04). The percentages of neutrophils (77 vs. 83%; p-value .001) and serum ferritin (439 vs. 688; p-value .0006) were higher during second wave, while lymphocyte counts were reduced (20 vs. 14%; p-value .0001). Hydroxychloroquine (11 vs. 0%; p-value .0001) and tocilizumab (7 vs. 0%; p-value .004) were more frequently prescribed during first wave, while utilization of dexamethasone (6 vs. 27%; p-value .0001) and remdesivir (47 vs. 65%; p-value .03) increased during the second wave. Mucormycosis (1.3 vs. 10%; p-value .01) and ICU admissions (20 vs. 37.2%; p-value .002) were more frequent during second wave. The 28-day mortality rate (9.6 vs. 10%; p-value 1) was not different., Conclusions: There has been a different clinical spectrum of COVID-19 amongst KTR with similar mortality between the two waves at a large Indian transplant centre., (© 2021 Asian Pacific Society of Nephrology.)

Approximately 90% of chronic typhoid carriers with persistent Salmonella enterica serovar Typhi (S. Typhi) gallbladder infection have gallstones. In Samoa, where typhoid fever has been endemic for many decades, risk factors predisposing to the development of gallstones are increasing among adults. The Samoa Typhoid Fever Control Program dispatches a "Typhoid Epidemiologic SWAT Team" to perform a household investigation of every blood culture-confirmed case of acute typhoid fever. Investigations include screening household contacts to detect chronic carriers. Following limited training, two nonexpert ultrasound operators performed point-of-care ultrasound (POCUS) on 120 Samoan adults from August to September 2019 to explore the feasibility of POCUS to detect individuals with gallstones during household investigations and community screenings. POCUS scans from 120 Samoan adults in three cohorts (28 food handlers, two typhoid cases and their 18 household contacts, and 72 attendees at an ambulatory clinic) were reviewed by a board-certified radiologist who deemed 96/120 scans (80%) to be interpretable. Compared with the radiologist (gold standard), the nonexpert operators successfully detected 6/7 Samoans with gallstones (85.7% sensitivity) and correctly identified 85/89 without gallstones (95.5% specificity). The proportion (24/120) of uninterpretable scans from this pilot that used minimally trained clinicians (who are neither radiologists nor ultrasound technicians) indicates the need for additional training of POCUS operators. Nevertheless, this pilot feasibility study engenders optimism that in the Samoan setting nonexperts can be trained to use POCUS to diagnose cholelithiasis, thereby helping (along with stool cultures and Vi serology) to identify possible chronic S. Typhi carriers.

Background and Aims: Caudal epidural and ultrasound-guided ilioinguinal, iliohypogastric nerve (IL/IH) blocks are commonly used regional anesthesia techniques for postoperative analgesia in pediatric inguinal surgeries. Dexmedetomidine as an adjuvant has been proven to prolong the duration of both neuraxial and peripheral nerve blocks. We compared the duration of analgesia provided by local anesthetic (LA) and dexmedetomidine for caudal and IL/IH block for pediatric inguinal surgeries., Material and Methods: Forty-six children undergoing inguinal hernia repair were selected for this randomized double-blind study. After general anesthesia, children received either 0.75 mL.kg -1 of 0.25% bupivacaine with 1 mcg.kg -1 of dexmedetomidine in caudal epidural or 0.25 mL.kg -1 of 0.25% bupivacaine with 1 mcg.kg -1 of dexmedetomidine in IL/IH block. The pain was assessed up to 24 h postoperatively using face, legs, activity, cry, consolability (FLACC) score. For FLACC ≥4, rescue analgesia was provided using 1 μg/kg of intravenous fentanyl, up to 2 h postoperatively and 10 mg/kg of oral ibuprofen between 2 and 24 postoperative hours. The time for first rescue analgesia was taken as the duration of analgesia., Results: There were no significant differences in the pain scores or analgesic utilization between the groups. The duration of analgesia of caudal and IL/IH blocks was similar (720.3 ± 430.1 min and 808.4 ± 453.1 min, respectively). The time taken for the performance of block was significantly higher for caudal compared to IL/IH (547 ± 93 vs. 317 ± 179 s; P < 0.001)., Conclusion: Both caudal epidural and USG-IL/IH block with dexmedetomidine as additive provide the comparable duration of postoperative analgesia with no significant side effects., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Journal of Anaesthesiology Clinical Pharmacology.)

Several recently published studies and consensus statements have demonstrated that there is only modest (and in many cases, low-quality) evidence that mobile health (mHealth) can improve patient clinical outcomes such as the length of stay or reduction of readmissions. There is also uncertainty as to whether mHealth can improve patient-centered outcomes such as patient engagement or patient satisfaction. One principal challenge behind the "effectiveness" research in this field is a lack of common understanding about what it means to be effective in the digital space (ie, what should constitute a relevant outcome and how best to measure it). In this viewpoint, we call for interdisciplinary, conceptual clarity on the definitions, methodologies, and patient-centered outcomes frequently used in mHealth research. To formulate our recommendations, we used a snowballing approach to identify relevant definitions, outcomes, and methodologies related to mHealth. To begin, we drew heavily upon previously published detailed frameworks that enumerate definitions and measurements of engagement. We built upon these frameworks by extracting other relevant measures of patient-centered care, such as patient satisfaction, patient experience, and patient activation. We describe several definitional inconsistencies for key constructs in the mHealth literature. In an effort to achieve clarity, we tease apart several patient-centered care outcomes, and outline methodologies appropriate to measure each of these patient-care outcomes. By creating a common pathway linking definitions with outcomes and methodologies, we provide a possible interdisciplinary approach to evaluating mHealth technologies. With the broader goal of creating an interdisciplinary approach, we also provide several recommendations that we believe can advance mHealth research and implementation., (©Courtenay Bruce, Patricia Harrison, Charlie Giammattei, Shetal-Nicholas Desai, Joshua R Sol, Stephen Jones, Roberta Schwartz. Originally published in JMIR mHealth and uHealth (http://mhealth.jmir.org), 11.11.2020.)

Background: Typhoid fever has been endemic on the island nation of Samoa (2016 population, 195 979) since the 1960s and has persisted through 2019, despite economic development and improvements in water supply and sanitation., Methods: Salmonella enterica serovar Typhi isolates from the 2 hospitals with blood culture capability and matched patient demographic and clinical data from January 2008 through December 2019 were analyzed. Denominators to calculate incidence by island, region, and district came from 2011 and 2016 censuses and from 2017-2019 projections from Samoa's Bureau of Statistics. Data were analyzed to describe typhoid case burden and incidence from 2008 to 2019 by time, place, and person., Results: In sum, 53-193 blood culture-confirmed typhoid cases occurred annually from 2008 to 2019, without apparent seasonality. Typhoid incidence was low among children age < 48 months (17.6-27.8/105), rose progressively in ages 5-9 years (54.0/105), 10-19 years (60.7-63.4/105), and 20-34 years (61.0-79.3/105), and then tapered off; 93.6% of cases occurred among Samoans < 50 years of age. Most typhoid cases and the highest incidence occurred in Northwest Upolu, but Apia Urban Area (served by treated water supplies) also exhibited moderate incidence. The proportion of cases from short-cycle versus long-cycle transmission is unknown. Samoan S. Typhi are pansusceptible to traditional first-line antibiotics. Nevertheless, enhanced surveillance in 2019 detected 4 (2.9%) deaths among 140 cases., Conclusions: Typhoid has been endemic in Samoa in the period 2008-2019. Interventions, including mass vaccination with a Vi-conjugate vaccine coadministered with measles vaccine are planned., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: Despite the growth of and media hype about mobile health (mHealth), there is a paucity of literature supporting the effectiveness of widespread implementation of mHealth technologies., Objective: This study aimed to assess whether an innovative mHealth technology system with several overlapping purposes can impact (1) clinical outcomes (ie, readmission rates, revisit rates, and length of stay) and (2) patient-centered care outcomes (ie, patient engagement, patient experience, and patient satisfaction)., Methods: We compared all patients (2059 patients) of participating orthopedic surgeons using mHealth technology with all patients of nonparticipating orthopedic surgeons (2554 patients). The analyses included Wilcoxon rank-sum tests, Kruskal-Wallis tests for continuous variables, and chi-square tests for categorical variables. Logistic regression models were performed on categorical outcomes and a gamma-distributed model for continuous variables. All models were adjusted for patient demographics and comorbidities., Results: The inpatient readmission rates for the nonparticipating group when compared with the participating group were higher and demonstrated higher odds ratios (ORs) for 30-day inpatient readmissions (nonparticipating group 106/2636, 4.02% and participating group 54/2048, 2.64%; OR 1.48, 95% CI 1.03 to 2.13; P=.04), 60-day inpatient readmissions (nonparticipating group 194/2636, 7.36% and participating group 85/2048, 4.15%; OR 1.79, 95% CI 1.32 to 2.39; P<.001), and 90-day inpatient readmissions (nonparticipating group 261/2636, 9.90% and participating group 115/2048, 5.62%; OR 1.81, 95% CI 1.40 to 2.34; P<.001). The length of stay for the nonparticipating cohort was longer at 1.90 days, whereas the length of stay for the participating cohort was 1.50 days (mean 1.87, SD 2 vs mean 1.50, SD 1.37; P<.001). Patients treated by participating surgeons received and read text messages using mHealth 83% of the time and read emails 84% of the time. Patients responded to 60% of the text messages and 53% of the email surveys. Patients were least responsive to digital monitoring questions when the hospital asked them to do something, and they were most engaged with emails that did not require action, including informational content. A total of 96% (558/580) of patients indicated high satisfaction with using mHealth technology to support their care. Only 0.40% (75/2059) patients opted-out of the mHealth technology program after enrollment., Conclusions: A novel, multicomponent, pathway-driven, patient-facing mHealth technology can positively impact patient outcomes and patient-reported experiences. These technologies can empower patients to play a more active and meaningful role in improving their outcomes. There is a deep need, however, for a better understanding of the interactions between patients, technology, and health care providers. Future research is needed to (1) help identify, address, and improve technology usability and effectiveness; (2) understand patient and provider attributes that support adoption, uptake, and sustainability; and (3) understand the factors that contribute to barriers of technology adoption and how best to overcome them., (©Courtenay R Bruce, Patricia Harrison, Tariq Nisar, Charlie Giammattei, Neema M Tan, Caitlin Bliven, Jamie Shallcross, Aroub Khleif, Nhan Tran, Sayali Kelkar, Noreen Tobias, Ana E Chavez, Dana Rivera, Angela Leong, Angela Romano, S Nicholas Desai, Josh R Sol, Kayla Gutierrez, Christopher Rappel, Eric Haas, Feibi Zheng, Kwan J Park, Stephen Jones, Paul Barach, Roberta Schwartz. Originally published in JMIR mHealth and uHealth (http://mhealth.jmir.org), 26.06.2020.)

Background: Cholera increases the risk of harmful effects on foetuses. We prospectively followed pregnant women unaware of their pregnancy status who received a study agent in a clinical trial evaluating the association between exposure to an oral cholera vaccine (OCV) and foetal survival., Methods: Study participants were selected from a randomized placebo-controlled trial conducted in Dhaka, Bangladesh. The vaccination campaign was conducted between January 10 and February 4, 2014. We enrolled women who were exposed to an OCV or placebo during pregnancy (Cohort 1) and women who were pregnant after the vaccination was completed (Cohort 2). Our primary endpoint was pregnancy loss (spontaneous miscarriage or stillbirth), and the secondary endpoints were preterm delivery and low birth weight. We employed a log-binomial regression to calculate the relative risk of having adverse outcomes among OCV recipients compared to that among placebo recipients., Result: There were 231 OCV and 234 placebo recipients in Cohort 1 and 277 OCV and 299 placebo recipients in Cohort 2. In Cohort 1, the incidence of pregnancy loss was 113/1000 and 115/1000 among OCV and placebo recipients, respectively. The adjusted relative risk for pregnancy loss was 0.97 (95% CI: 0.58-1.61; p = 0.91) in Cohort 1. We did not observe any variation in the risk of pregnancy loss between the two cohorts. The risks for preterm delivery and low birth weight were not significantly different between the groups in both cohorts., Conclusions: Our study provides additional evidence that exposure to an OCV during pregnancy does not increase the risk of pregnancy loss, preterm delivery, or low birth weight, suggesting that pregnant women in cholera-affected regions should not be excluded in a mass vaccination campaign., Trial Registration: The study is registered at ( http://clinicaltrials.gov ). Identifier: NCT02027207 .

Anorectal malformations (ARM) include congenital anomalies of the distal anus and rectum with or without anomalies of the urogenital tract. Posterior sagittal anorectoplasty (PSARP) and minimally invasive laparoscopically assisted anorectal pull-through (LAARP) procedure are now mainly used to surgically treat ARMs. Magnetic resonance imaging (MRI) is the modality of choice for interval follow-up assessment of structural and functional outcome after these surgeries to assess future bowel continence. Well-developed pelvic musculature has been found to be a reflector of better anal continence after ARM surgery. Thus, MRI plays an important role in evaluating the external sphincter complex, puborectalis, and levator ani muscles. Other parameters that need to be noted include the position of the neoanus, rectal diameter, anorectal angle, presence or absence of megarectum, and other ancillary anomalies in the spine. Thus, MRI due to superior soft-tissue resolution is the modality of choice and indispensable for post-operative pelvic evaluation in children.

Purpose of Review: The purpose of this article is to review age-associated alterations in microbiota composition, diversity and functional features in context of immune senescence, chronic inflammation and comorbidities associated with HIV infection. The overall goal is to assess whether modulating the microbiome will likely improve resilience of the immune system and augment return to health., Recent Findings: Alteration in the gut microbiota composition diversity and function occur in HIV and aging. Importantly, butyrate producing bacteria are reduced in both HIV and aging individuals. There is increasing relevance of studying metabolomics in the context of HIV-associated non-AIDS comorbidities and aging. Interventional prospects of probiotics, prebiotics and fecal microbiota transplantation in HIV and aging will provide novel therapeutic approaches., Summary: Increasing evidence suggests a significant link in changes in the composition, diversity and functional aspects of intestinal microbiome with normal aging and HIV infection. Data on association of metabolites produced by the microbiome with HIV-associated non-AIDS comorbidities is mounting. The impact of the microbiome alterations on inflammation, immune and organ senescence and mechanisms by which bio-behavioral pathways will exacerbate these outcomes needs to be further evaluated.

Background: HIV/hepatitis C-coinfected persons experience more rapid liver disease progression than hepatitis C virus (HCV) monoinfected persons, even in the setting of potent antiretroviral therapy., Methods: We sought to articulate the role of macrophage activation and inflammation in liver disease progression by measuring serial soluble markers in HIV/HCV-coinfected women. We compared markers measured during retrospectively defined periods of rapid liver disease progression to periods where little or no liver disease progression occurred. Liver disease progression was defined by liver biopsy, liver-related death or the serum markers AST-to-platelet ratio index and FIB-4. Soluble CD14, sCD163, lipopolysaccharide (LPS), tumor necrosis factor (TNF) receptor II, interleukin-6, and chemokine ligand 2 (CCL 2) were measured at 3 time points over 5 years., Results: One hundred six time intervals were included in the analysis: including 31 from liver disease progressors and 75 from nonprogressors. LPS, sCD14, interleukin-6, and CCL2 levels did not differ in slope or quantity over time between rapid liver disease progressors and nonprogressors. TNFRII and sCD163 were significantly higher in liver disease progressors at (P = 0.002 and <0.0001 respectively) and preceding (P = 0.01 and 0.003 respectively) the liver fibrosis outcome in unadjusted models, with similar values when adjusted for HIV RNA and CD4 count., Conclusions: In women with HIV/HCV coinfection, higher sCD163 levels, a marker of macrophage activation, and TNFRII levels, implying activation of the TNF-α system, were associated with liver disease progression. Our results provide an addition to the growing body of evidence regarding the relationship between macrophage activation, inflammation, and liver disease progression in HIV/HCV coinfection.

Purpose: Transient elastography (TE) is routinely used for noninvasive staging of hepatic fibrosis. The objective of the present study was to investigate the role of TE (FibroScan) in determining changes in liver congestion in patients with Budd-Chiari syndrome (BCS) treated by endovascular interventions and determine the effects of pretreatment Meta-analysis of Histological Data in Viral Hepatitis (METAVIR) fibrosis score on posttreatment liver stiffness (LS)., Materials and Methods: Twenty-five patients undergoing endovascular procedures for treatment of BCS underwent TE immediately before and within 24 hours after the procedure. Fifteen patients available for 3-month follow-up were again subjected to TE. Mean LS values before and after intervention were compared in 12 of these patients for whom METAVIR scores were available. Pressure gradient changes across the stenosed hepatic veins/inferior vena cava were measured during the procedure. Statistical analysis of these data was performed by Wilcoxon signed-rank test, Mann-Whitney U test, and Pearson product-moment correlation coefficient., Results: Significant differences were found between mean LS measurements before and within 24 hours after intervention (Z-score = 4.372) and between the mean values obtained before and 3 months after treatment (Z-score = 3.408). Mean changes in LS values after intervention in patients with METAVIR fibrosis scores ≤ 2 and > 2 were not significant. There was no correlation between changes in pressure gradients and the degree of LS., Conclusions: TE is a useful tool to assess the reduction in hepatic congestion in patients with BCS undergoing endovascular interventions., (Copyright © 2017 SIR. Published by Elsevier Inc. All rights reserved.)

Improving water and sanitation is the preferred choice for cholera control in the long-term. Nevertheless, vaccination is an available tool that has been shown to be a cost-effective option for cholera prevention in endemic countries or during outbreaks. In 2011 the first low-cost oral cholera vaccine for international use was given prequalification by the World Health Organization (WHO). To increase and prioritize use of the vaccine, WHO created a global stockpile in 2013 from which countries may request oral cholera vaccine for reactive campaigns. WHO has issued specific guidelines for applying for the vaccine, which was previously in short supply (despite prequalification for a second oral vaccine in 2015). The addition of a third WHO-prequalified oral cholera vaccine in 2016 is expected to increase the global stockpile considerably and alleviate supply issues. However, prioritization and best use of the vaccine (e.g. how, when and where to use) will remain challenges. We describe 12 past oral cholera vaccine campaigns, conducted in settings with varying burdens of cholera. These case studies illustrate three key challenges faced in the use of the oral cholera vaccines: regulatory hurdles, cold chain logistics and vaccine coverage and uptake. To pave the way for the introduction of current and future oral cholera vaccines, we discuss operational challenges and make recommendations for future research with respect to each of these challenges.

Cholera remains an important but neglected public health threat, affecting the health of the poorest populations and imposing substantial costs on public health systems. Cholera can be eliminated where access to clean water, sanitation, and satisfactory hygiene practices are sustained, but major improvements in infrastructure continue to be a distant goal. New developments and trends of cholera disease burden, the creation of affordable oral cholera vaccines (OCVs) for use in developing countries, as well as recent evidence of vaccination impact has created an increased demand for cholera vaccines. The global OCV stockpile was established in 2013 and with support from Gavi, has assisted in achieving rapid access to vaccine in emergencies. Recent WHO prequalification of a second affordable OCV supports the stockpile goals of increased availability and distribution to affected populations. It serves as an essential step toward an integrated cholera control and prevention strategy in emergency and endemic settings.

Background: Transdermal buprenorphine, which is used in chronic pain management, has rarely been studied for use in acute pain management. The aim of this study was to compare the safety and efficacy of transdermal buprenorphine patch to oral tramadol for post-operative analgesia, following proximal femur surgeries., Methodology: Fifty adult patients undergoing surgery for hip fracture under spinal anaesthesia were included in this study. One group (Group TDB) received transdermal buprenorphine 10 mcg/h patch applied a day before the surgery and other group received oral tramadol 50 mg three times a day for analgesia (Group OT). They were allowed to take diclofenac and paracetamol tablets for rescue analgesia. Pain scores at rest, on movement, rescue analgesic requirement and side effects were compared between the groups over 7 days. Chi-square and independent sample t -test were used for categorical and continuous variables, respectively., Results: Resting pain scores and pain on movement were significantly lower in TDB Group on all 7 days starting from 24 h post-operatively. Rescue analgesic requirement was significantly lower in TDB Group compared to OT Group. All the patients needed rescue analgesic in OT Group whereas 68% of the patients needed the same in TDB Group. Incidence of vomiting was less and satisfaction scores were much higher in TDB Group as compared to OT Group (79% vs. 66%, P < 0.001)., Conclusion: Transdermal buprenorphine can be safely used for post-operative analgesia and is more efficacious in reducing post-operative pain after 24 hours, with fewer side effects when compared to oral tramadol., Competing Interests: There are no conflicts of interest.

Background: A variety of techniques have been described for the axillary block using nerve stimulator, either with single injection, two, three, or four separate injections. Identification of all the four nerves is more difficult and time-consuming than other methods., Aims: Aim of the present study is to compare success rate, onset, and duration of sensory and motor anesthesia of axillary block using nerve stimulator, either with single injection after identification of any one of the four nerves or four separate injections following identification of each of nerve., Setting and Design: Prospective, randomized, double-blind study. Patients undergoing forearm and hand surgeries under axillary block., Methodology: One hundred patients, aged 18-75 years, were randomly allocated into two groups of 50 each. Axillary block was performed under the guidance of nerve stimulator with a mixture of 18 ml of 1.5% lignocaine and 18 ml of 0.5% bupivacaine. In the first group ( n = 50), all 36 ml of local anesthetic was injected after the identification of motor response to any one of the nerves and in Group 2, all the four nerves were identified by the motor response, and 9 ml of local anesthetic was injected at each of the nerves. The success rate of the block, onset, and duration of sensory and motor block was assessed., Statistical Analysis: Categorical variables were compared using the Chi-square test, and continuous variables were compared using independent t -test., Results: The success rate of the block with four injection technique was higher compared to single-injection technique (84% vs. 56%, P = 0.02). Four injection groups had a faster onset of sensory and motor block and prolonged duration of analgesia compared to single-injection group ( P < 0.001). There were no significant differences in the incidence of accidental arterial puncture and hemodynamic parameter between the groups., Conclusion: Identification of all the four nerves produced higher success rate and better quality of the block when compared to single-injection technique., Competing Interests: There are no conflicts of interest.

HCV and HIV independently lead to immune dysregulation. The mechanisms leading to advanced liver disease progression in HCV/HIV coinfected subjects remain unclear.In this cross-sectional study, we assessed the association of HCV viremia, liver fibrosis, and immune response patterns in well-characterized HIV phenotypes: Elite controllers (Elites), HIV controlled (ARTc), and HIV uncontrolled (ARTuc) matched by age and race. Groups were stratified by HCV RNA status. Regulatory T-cell frequencies, T-cell activation (HLADR+CD38+), apoptosis (Caspase-3+), and intracellular cytokines (interferon-γ, IL-2, IL-17) were assessed using multiparametric flow-cytometry. Liver fibrosis was scored by AST to platelet ratio index (APRI).We found liver fibrosis (APRI) was 50% lower in Elites and ARTc compared to ARTuc. Higher liver fibrosis was associated with significantly low CD4+ T cell counts (P < 0.001, coefficient r = -0.463). Immune activation varied by HIV phenotype but was not modified by HCV viremia. HCV viremia was associated with elevated CD8 T-cell Caspase-3 in Elites, ARTuc, and HIV- except ARTc. CD8 T-cell Caspase-3 levels were significantly higher in HCV RNA+ Elites (P = 0.04) and ARTuc (P = 0.001) and HIV- groups (P = 0.02) than ARTc. Importantly, ARTuc HCV RNA+ had significantly higher CD4 T-cell interleukin-17 levels than ARTuc HCV RNA- (P = 0.005).HIV control was associated with lower liver fibrosis in HCV/HIV co-infected women. HCV viremia is associated with an inflammatory CD4 TH-17 phenotype in absence of HIV control and higher frequency of pro-apoptosis CD8 T-cells critical to avert progression of HIV and HCV disease that is attenuated in ART controllers. Elite controllers with HCV viremia are more prone to CD8 T-cell apoptosis than ART controllers, which could have negative consequences over time, highlighting the importance of ART control in HCV/HIV coinfected individuals.

Extrahepatic portal vein obstruction (EHPVO) is a primary vascular condition characterized by chronic long standing blockage and cavernous transformation of portal vein with or without additional involvement of intrahepatic branches, splenic or superior mesenteric vein. Patients generally present in childhood with multiple episodes of variceal bleed and EHPVO is the predominant cause of paediatric portal hypertension (PHT) in developing countries. It is a pre-hepatic type of PHT in which liver functions and morphology are preserved till late. Characteristic imaging findings include multiple parabiliary venous collaterals which form to bypass the obstructed portal vein with resultant changes in biliary tree termed portal biliopathy or portal cavernoma cholangiopathy. Ultrasound with Doppler, computed tomography, magnetic resonance cholangiography and magnetic resonance portovenography are non-invasive techniques which can provide a comprehensive analysis of degree and extent of EHPVO, collaterals and bile duct abnormalities. These can also be used to assess in surgical planning as well screening for shunt patency in post-operative patients. The multitude of changes and complications seen in EHPVO can be addressed by various radiological interventional procedures. The myriad of symptoms arising secondary to vascular, biliary, visceral and neurocognitive changes in EHPVO can be managed by various radiological interventions like transjugular intra-hepatic portosystemic shunt, percutaneous transhepatic biliary drainage, partial splenic embolization, balloon occluded retrograde obliteration of portosystemic shunt (PSS) and revision of PSS.

Background: A single-dose regimen of the current killed oral cholera vaccines that have been prequalified by the World Health Organization would make them more attractive for use against endemic and epidemic cholera. We conducted an efficacy trial of a single dose of the killed oral cholera vaccine Shanchol, which is currently given in a two-dose schedule, in an urban area in which cholera is highly endemic., Methods: Nonpregnant residents of Dhaka, Bangladesh, who were 1 year of age or older were randomly assigned to receive a single dose of oral cholera vaccine or oral placebo. The primary outcome was vaccine protective efficacy against culture-confirmed cholera occurring 7 to 180 days after dosing. Prespecified secondary outcomes included protective efficacy against severely dehydrating culture-confirmed cholera during the same interval, against cholera and severe cholera occurring 7 to 90 versus 91 to 180 days after dosing, and against cholera and severe cholera according to age at baseline., Results: A total of 101 episodes of cholera, 37 associated with severe dehydration, were detected among the 204,700 persons who received one dose of vaccine or placebo. The vaccine protective efficacy was 40% (95% confidence interval [CI], 11 to 60%; 0.37 cases per 1000 vaccine recipients vs. 0.62 cases per 1000 placebo recipients) against all cholera episodes, 63% (95% CI, 24 to 82%; 0.10 vs. 0.26 cases per 1000 recipients) against severely dehydrating cholera episodes, and 63% (95% CI, -39 to 90%), 56% (95% CI, 16 to 77%), and 16% (95% CI, -49% to 53%) against all cholera episodes among persons vaccinated at the age of 5 to 14 years, 15 or more years, and 1 to 4 years, respectively, although the differences according to age were not significant (P=0.25). Adverse events occurred at similar frequencies in the two groups., Conclusions: A single dose of the oral cholera vaccine was efficacious in older children (≥5 years of age) and in adults in a setting with a high level of cholera endemicity. (Funded by the Bill and Melinda Gates Foundation and others; ClinicalTrials.gov number, NCT02027207.).

Xanthogranulomatous cholecystitis (XGC) is an uncommon variant of chronic cholecystitis characterized by xanthogranulomatous inflammation of the gallbladder. Intramural accumulation of lipid-laden macrophages and acute and chronic inflammatory cells is the hallmark of the disease. The xanthogranulomatous inflammation of the gallbladder can be very severe and can spill over to the neighbouring structures like liver, bowel and stomach resulting in dense adhesions, perforation, abscess formation, fistulous communication with adjacent bowel. Striking gallbladder wall thickening and dense local adhesions can be easily mistaken for carcinoma of the gallbladder, both intraoperatively as well as on preoperative imaging. Besides, cases of concomitant gallbladder carcinoma complicating XGC have also been reported in literature. So, we have done a review of the imaging features of XGC in order to better understand the entity as well as to increase the diagnostic yield of the disease summarizing the characteristic imaging findings and associations of XGC. Among other findings, presence of intramural hypodense nodules is considered diagnostic of this entity. However, in some cases, an imaging diagnosis of XGC is virtually impossible. Fine needle aspiration cytology might be handy in such patients. A preoperative counselling should include possibility of differential diagnosis of gallbladder cancer in not so characteristic cases.

Studies on safety, immunogenicity and efficacy of the killed, bivalent whole cell oral cholera vaccine (Shanchol) have been conducted in historically endemic settings of Asia. Recent cholera vaccination campaigns in Haiti and Guinea have also demonstrated favourable immunogenicity and effectiveness in nonendemic outbreak settings. We performed a secondary analysis, comparing immune responses of Shanchol from two randomised controlled trials performed in an endemic and a less endemic area (Addis Ababa) during a nonoutbreak setting. While Shanchol may offer some degree of immediate protection in primed populations living in cholera endemic areas, as well as being highly immunogenic in less endemic settings, understanding the characteristics of immune responses in each of these areas is vital in determining ideal dosing strategies that offer the greatest public health impact to populations from areas with varying degrees of cholera endemicity., (© 2015 John Wiley & Sons Ltd.)

Background: Currently, there are two oral cholera vaccines (OCV) that are prequalified by the World Health Organization. Both (Dukoral and Shanchol) have been proven to be safe, immunogenic, and effective. As the global supply of OCV remains limited, we assessed the safety and immunogenicity of a new low cost, killed, bivalent OCV (Euvichol) in the Philippines., Methods: The randomized controlled trial was carried out in healthy Filipino adults and children. Two doses of either the current WHO prequalified OCV (Shanchol) or the same composition OCV being considered for WHO prequalification (Euvichol) were administered to participants., Results: The pivotal study was conducted in total of 1263 healthy participants (777 adults and 486 children). No serious adverse reactions were elicited in either vaccine groups. Vibriocidal antibody responses to V. cholerae O1 Inaba following administration of two doses of Euvichol were non-inferior to those of Shanchol in adults (82% vs 76%) and children (87% vs 89%). Similar findings were observed for O1 Ogawa in adults (80% vs 74%) and children (91% vs 88%)., Conclusion: A two dose schedule with Euvichol induces a strong vibriocidal response comparable to those elicited by the currently WHO prequalified OCV, Shanchol. Euvichol will be an oral cholera vaccine suitable for use in lower income countries, where cholera still has a significant economic and public health impact., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Killed whole-cell oral cholera vaccine (OCV) has been a key component of a comprehensive package including water and sanitation measures for recent cholera epidemics. The vaccine, given in a two-dose regimen, has been evaluated in a large number of human volunteers in India, Vietnam, and Bangladesh, where it has demonstrated safety, immunogenicity, and clinical efficacy. We conducted a double-blind randomized placebo-controlled trial in Ethiopia, where we evaluated the safety and immunogenicity of the vaccine in 216 healthy adults and children. OCV was found to be safe and elicited a robust immunological response against Vibrio cholerae O1, with 81% adults and 77% children demonstrating seroconversion 14 days after the second dose of vaccine. This is the first study to evaluate safety and immunogenicity of the vaccine in a population outside Asia using a placebo-controlled, double-blind, randomized study design., (© The American Society of Tropical Medicine and Hygiene.)

Background: The bivalent killed oral cholera vaccine (OCV) provides 65% cumulative protection over five years. It remains unknown whether a boosting regimen can maintain protection in previously immunized populations. This study examines the immunogenicity and safety of an OCV regimen given five years following initial dosing., Methodology/principal Findings: An open label controlled trial was conducted in 426 healthy Indian participants previously enrolled in a large efficacy trial. To assess whether an OCV regimen given after five years can elicit an antibody response equal to that of a primary series, we compared vibriocidal antibody titers in previously immunized participants receiving a two dose booster regimen to participants receiving a primary two dose immunization series. Among participants receiving a two dose primary series of OCV (n = 186), 69% (95% CI 62%-76%) seroconverted. In the intervention arm (n = 184), 66% (95% CI 59%-73%) seroconverted following a two dose boosting schedule given five years following the initial series. Following a single boosting dose, 71% (95% CI 64%-77%) seroconverted. Children demonstrated 79% (95% CI 69%-86%) and 82% (95% CI 73%-88%) seroconversion after primary and boosting regimens, respectively., Conclusions/significance: Administration of an OCV boosting regimen elicits an immune response similar to those receiving a primary series in endemic areas. Though a single boosting dose induces a strong immune response, further investigations are needed to measure if these findings translate to clinical protection.

Phycobilisomes present in cyanobacteria are photosynthetic macromolecular protein complexes that are categorized into three types - phycoerythrins (high energy), phycocyanin (intermediate energy) and allophycocyanin (low energy). Structurally, they consist of α and β protein subunits and open chain tetrapyrrole prosthetic group (bilin chromophore), known for its antioxidant properties and therapeutic potential against a variety of physiological ailments. Phycoerythrins (C-PE) were purified from cyanobacterial strains Phormidium sp. A27DM and Halomicronema sp. A32DM and their respective apoptotic potentials were assessed on A549 human lung carcinoma cells. Both strains of cyanobacteria were cultured and the C-PE from each strain was extracted, quantified and characterized. C-PE accounted for a dose dependent decrement in cell viability, mitochondrial membrane potential and an increment in lactate dehydrogenase release. Higher doses of C-PE (of both strains) accounted for loss of cell viability and nuclear pycnosis. These findings were further substantiated with flow cytometry that revealed a cell arrest at G0/G1 phase and a high percentage of cells undergoing apoptosis following C-PE treatment. These results confirm the efficacy of C-PE from Phormidium sp. or Halomicronema sp. in triggering apoptotic cell death. This study is the first to report on apoptotic property of C-PE against A549 human lung carcinoma cells and warrants further studies to establish its anti-cancer potential.

Background: A bivalent killed whole cell oral cholera vaccine has been found to be safe and efficacious for five years in the cholera endemic setting of Kolkata, India, when given in a two dose schedule, two weeks apart. A randomized controlled trial revealed that the immune response was not significantly increased following the second dose compared to that after the first dose. We aimed to evaluate the impact of an extended four week dosing schedule on vibriocidal response., Methodology/principal Findings: In this double blind randomized controlled non-inferiority trial, 356 Indian, non-pregnant residents aged 1 year or older were randomized to receive two doses of oral cholera vaccine at 14 and 28 day intervals. We compared vibriocidal immune responses between these schedules. Among adults, no significant differences were noted when comparing the rates of seroconversion for V. cholerae O1 Inaba following two dose regimens administered at a 14 day interval (55%) vs the 28 day interval (58%). Similarly, no differences in seroconversion were demonstrated in children comparing the 14 (80%) and 28 day intervals (77%). Following 14 and 28 day dosing intervals, vibriocidal response rates against V. cholerae O1 Ogawa were 45% and 49% in adults and 73% and 72% in children respectively. Responses were lower for V. cholerae O139, but similar between dosing schedules for adults (20%, 20%) and children (28%, 20%)., Conclusions/significance: Comparable immune responses and safety profiles between the two dosing schedules support the option for increased flexibility of current OCV dosing. Further operational research using a longer dosing regimen will provide answers to improve implementation and delivery of cholera vaccination in endemic and epidemic outbreak scenarios.

One of every 5 children does not receive basic vaccines because of concerns related to storage and delivery in resource limited countries. Transporting vaccines over long distances in extreme temperatures is a common challenge. Issues that involve production and formulation, delivery technologies, cold chain logistics, and safety factors need to be addressed to properly adapt vaccines to resource constrained settings. Current successful field interventions include United Nation Children's Fund cold boxes, which are used to store and distribute vaccine in disaster struck areas, and vaccine vial monitors, which allow health workers to gauge whether vaccine is still usable in areas with unreliable electricity and refrigeration. This review aims to provide a general overview of innovative approaches and technologies that positively affect vaccine coverage and save more lives., (© American Academy of Pediatrics, 2014. All rights reserved.)

Background and Objectives: A review of all the adjuncts for intravenous regional anaesthesia concluded that there is good evidence to recommend NonSteroidal Anti-Inflammatory agents and pethidine in the dose of 30mg dose as adjuncts to intravenous regional anaesthesia. But there are no studies to compare pethidine of 30mg dose to any of the NonSteroidal Anti-Inflammatory agents., Methods: In a prospective, randomized, double blind study, 45 patients were given intravenous regional anaesthesia with either lignocaine alone or lignocaine with pethidine 30mg or lignocaine with ketprofen 100mg. Fentanyl was used as rescue analgesic during surgery. For the first 6h of postoperative period analgesia was provided by fentanyl injection and between 6 and 24h analgesia was provided by diclofenac tablets. Visual analogue scores for pain and consumption of fentanyl and diclofenac were compared., Results: The block was inadequate for one case each in lignocaine group and pethidine group, so general anaesthesia was provided. Time for the first dose of fentanyl required for postoperative analgesia was significantly more in pethidine and ketoprofen groups compared to lignocaine group (156.7±148.8 and 153.0±106.0 vs. 52.1±52.4min respectively). Total fentanyl consumption in first 6 h of postoperative period was less in pethidine and ketoprofen groups compared to lignocaine group (37.5±29.0 mcg, 38.3±20.8mcg vs. 64.2±27.2mcg respectively). Consumption of diclofenac tablets was 2.4±0.7, 2.5±0.5 and 2.0±0.7 in the control, pethidine and ketoprofen group respectively, which was statistically not significant. Side effects were not significantly different between the groups., Conclusion: Both pethidine and ketoprofen are equally effective in providing postoperative analgesia up to 6h, without significant difference in the side effects and none of the adjuncts provide significant analgesia after 6h., (Copyright © 2013 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.)

The emergence of sphingosine-1-phosphate lyase (SPL) as a promising therapeutic target for inflammatory diseases has heightened interest in the identification of small molecules that modulate its activity. The enzymatic activity of SPL is typically measured using radiometric or fluorescence-based assays that require a lipid extraction step, or by direct quantitation of reaction products using mass spectrometry (MS). To facilitate testing large numbers of compounds to identify SPL modulators, we developed a robust scintillation proximity assay (SPA) that is compatible with high-throughput screening (HTS). This assay employs recombinant human full-length SPL in insect cell membrane preparations to catalyze the conversion of biotinylated aminosphingosine-1-[(33)P]phosphate (S1(33)P-biotin) to trans-2-hexadecenal-biotin and ethanolamine [(33)P]phosphate. To validate the SPA and confirm the fidelity of its measurement of SPL enzyme activity, we developed a Rapid-Fire MS method that quantitates nonradiolabeled S1P-biotin. In addition, we developed a simple, scalable method to produce S1(33)P-biotin in quantities sufficient for HTS. The optimized SPA screen in 384-well microplates produced a mean plate-wise Z'-statistic of 0.58 across approximately 3,000 plates and identified several distinct structural classes of SPL inhibitor. Among the inhibitors that the screen identified was one compound with an IC50 of 1.6 μM in the SPA that induced dose-dependent lymphopenia in mice.

Background: Typhoid fever remains a major health problem in the developing world. Intestinal perforation is a lethal complication and continues to occur in impoverished areas despite advances in preventive and therapeutic strategies., Objectives: To estimate the case fatality rate (CFR) and length of hospital stay among patients with typhoid intestinal perforation in developing countries., Data Sources: Peer-reviewed publications listed in PubMed and Google Scholar., Study Eligibility: The publications containing data on CFR or length of hospitalization for typhoid fever from low, lower middle and upper middle income countries based on World Bank classification. Limits are English language, human research and publication date from 1st January 1991 to 31st December 2011., Participants: Subjects with reported typhoid intestinal perforation., Interventions: None, standard practice as reported in the publication., Study Appraisal and Synthesis Methods: Systematic literature review followed by meta-analysis after regional classification on primary data. Descriptive methods were applied on secondary data., Results: From 42 published reports, a total of 4,626 hospitalized typhoid intestinal perforation cases and 706 deaths were recorded (CFR = 15·4%; 95% CI; 13·0%-17·8%) with a significant regional differences. The overall mean length of hospitalization for intestinal perforation from 23 studies was 18.4 days (N = 2,542; 95% CI; 15.6-21.1)., Limitations: Most typhoid intestinal perforation studies featured in this review were from a limited number of countries., Conclusions: The CFR estimated in this review is a substantial reduction from the 39.6% reported from a literature review for years 1960 to 1990. Aggressive resuscitation, appropriate antimicrobial coverage, and prompt surgical intervention may have contributed to decrease mortality., Implications: The quantification of intestinal perforation outcomes and its regional disparities as presented here is valuable in prioritizing and targeting typhoid-preventive interventions to the most affected areas.

When oral vaccines are administered to children in lower- and middle-income countries, they do not induce the same immune responses as they do in developed countries. Although not completely understood, reasons for this finding include maternal antibody interference, mucosal pathology secondary to infection, malnutrition, enteropathy, and previous exposure to the organism (or related organisms). Young children experience a high burden of cholera infection, which can lead to severe acute dehydrating diarrhea and substantial mortality and morbidity. Oral cholera vaccines show variations in their duration of protection and efficacy between children and adults. Evaluating innate and memory immune response is necessary to understand V. cholerae immunity and to improve current cholera vaccine candidates, especially in young children. Further research on the benefits of supplementary interventions and delivery schedules may also improve immunization strategies.

In this study, we demonstrate the antibacterial activity of P128 on Staphylococcus isolates responsible for canine pyoderma. Eighty seven swabs were collected from dogs suffering from pyoderma and subjected to antibiotic sensitivity test and 46 Staphylococcus strains were isolated and characterized. In-vitro antimicrobial susceptibility testing with P128 was done by Minimum Inhibitory Concentration (MIC) method as per CLSI guidelines. All the Staphylococci isolated from the dogs with pyoderma, although showed resistance to various antibiotics tested, were lysed by P128. Clinical efficacy of P128 was examined in 17 dogs with pyoderma by application of the P128 hydrogel twice daily for 8 days and the results indicated complete healing of all the lesions of all the dogs under treatment. Under the conditions of this study, P128 was found to be a potent convenient proteinaceous drug for the treatment of staphylococcal pyoderma in dogs.

Background: Microbial translocation has been implicated in the pathogenesis of liver fibrosis and cirrhosis. We sought to determine whether markers of microbial translocation are associated with liver disease progression during coinfection with human immunodeficiency virus (HIV) and hepatitis C virus (HCV)., Methods: We measured serial plasma lipopolysaccharide (LPS), endotoxin core antibody, intestinal fatty acid-binding protein (I-FABP), soluble CD14 (sCD14), interleukin 6 (IL-6), interleukin 10, and tumor necrosis factor α (TNF-α) levels over a 5-year period in 44 HIV/HCV-coinfected women, 21 of whom experienced liver disease progression and 23 were nonprogressors., Results: While LPS levels did not differ significantly over time between progressors and nonprogressors (P = .60), progressors had significantly higher plasma levels of sCD14, a marker of monocyte activation by LPS, at the first time point measured (P = .03) and throughout the study period (P = .001); progressors also had higher IL-6 and I-FABP levels over the 5-year study period (P = .02 and .03, respectively). The associations between progression and sCD14, I-FABP, and IL-6 levels were unchanged in models controlling for HIV RNA and CD4(+) T-cell count., Conclusions: Although LPS levels did not differ between liver disease progressors and nonprogressors, the association of sCD14, I-FABP, and IL-6 levels with liver disease progression suggests that impairment of gut epithelial integrity and consequent microbial translocation may play a role in the complex interaction of HIV and HCV pathogenesis.

GB virus C (GBV-C), a pan-lymphotropic flavivirus capable of persistent infection, is associated with prolonged survival and reduced T-cell activation in HIV-infected patients. GBV-C was associated with reduced CD56brt/CD16- natural killer cell and monocyte activation, and a trend toward reduced B-cell activation by measuring cell surface activation markers or HIV entry coreceptors. The GBV-C association was independent of HIV viral load. Thus, GBV-C may influence non-T-cell immune activation in individuals with HIV infection.

Sphingosine-1-phosphate (S1P) receptors are critical for lymphocyte egress from secondary lymphoid organs, and S1P receptor modulators suppress lymphocyte circulation. However, the role of S1P receptors on monocytes is less clear. To elucidate this, we systematically evaluated monocytes in rats and mice, both in naive and inflammatory conditions, with S1P receptor modulators FTY720 and BAF312. We demonstrate that S1P receptor modulators reduce circulating monocytes in a similar time course as lymphocytes. Furthermore, total monocyte numbers were increased in the spleen and bone marrow, suggesting that S1P receptor modulation restricts egress from hematopoietic organs. Monocytes treated ex vivo with FTY720 had reduced CD40 expression and TNF-α production, suggesting a direct effect on monocyte activation. Similar reductions in protein expression and cytokine production were also found in vivo. Suppression of experimental autoimmune encephalomyelitis in mice and rats by FTY720 correlated with reduced numbers of lymphocytes and monocytes. These effects on monocytes were independent of S1P3, as treatment with BAF312, a S1P1,4,5 modulator, led to similar results. These data reveal a novel role for S1P receptors on monocytes and offer additional insights on the mechanism of action of S1P receptor modulators in disease.