Impact of human immunodeficiency virus type 1 subtypes on virologic response and emergence of drug resistance among children in the Paediatric European Network for Treatment of AIDS (PENTA) 5 trial

The association between virologic response and human immunodeficiency virus type 1 (HIV-1) subtype was investigated in 113 HIV-1-infected children randomly assigned to receive zidovudine plus lamivudine, zidovudine plus abacavir, or lamivudine plus abacavir in the Paediatric European Network for Treatment of AIDS (PENTA) 5 trial. Symptomatic children (n=68) also received nelfinavir; asymptomatic children (n=45) were randomly assigned to receive nelfinavir or placebo. HIV-1 subtypes A, B, C, D, F, G, H, A/E, and A/G were found in 15%, 41%, 16%, 9%, 5%, 2%, 1%, 5%, and 7% of the children, respectively. Resistance assay failure rates were higher for non-B subtypes than for B subtypes (genotype, P=.01; phenotype, P=.02). HIV-1 subtype was not associated with virologic response at 24 and 48 weeks after initiation of treatment. No differences were observed in the frequency of development of resistance mutations L90M (P=1.00) and D30N (P=.61) in B and non-B viruses. In conclusion, no evidence that subtype determined virologic response to therapy was found.     

A survey-based assessment of the Canadian pediatric surgery workforce

Background

There is significant lack of information regarding the Canadian pediatric surgery workforce.

Methods

An IRB-approved survey aimed at assessing workforce issues was administered to pediatric surgeons and pediatric surgery chiefs in Canada in 2012.

Results

The survey was completed by 98% of practicing surgeons and 13 of the 18 division chiefs. Only 6% of surgeons are older than 60 years, and only a fifth anticipate retirement over the next decade. The workforce is stable, with 82% of surgeons unlikely to change current positions. Surgical volume showed essentially no growth during the 5-year period 2006–2010. The majority of surgeons felt they were performing the right number or too few cases and anticipated minimal or no future growth in their individual practices or that of their group. Based on anticipated vacancies, the best estimate is a need for 20 new pediatric surgeons over the next decade. This need is significantly surpassed by the current output from the Canadian training programs.

Conclusions

The Canadian pediatric surgery workforce is currently saturated. The mismatch between the number of graduating trainees and the available positions over the next decade has significant repercussions for current surgery and pediatric surgery residents wishing to practice in Canada.     

Anti-melanin deposition activity and active constituents of Jatropha multifida stems

Journal of Natural Medicines - Jatropha multifida is a medicinal plant that belongs to the Euphorbiaceae family. Our investigation revealed that the chloroform extract of J. multifida stems showed...     

Evidence that the LRRK2 ROC domain Parkinson's disease‐associated mutants A1442P and R1441C exhibit increased intracellular degradation

Mutations in the leucine‐rich repeat kinase 2 (lrrk2) gene are the leading genetic cause of Parkinson's disease (PD). In characterizing the novel ROC domain mutant A1442P, we compared its steady‐state protein levels, propensity to aggregate, and toxicity with the pathogenic R1441C mutant and wild‐type (WT) LRRK2. Mutant (R1441C and A1442P) and WT LRRK2 fused to green fluorescent protein (GFP) and FLAG were transiently expressed in HEK293 cells using plasmid constructs. Western analysis and fluorescence microscopy consistently demonstrated lower mutant LRRK2 protein levels compared with WT. A time‐course expression study using flow cytometry showed that WT LRRK2 expression increased initially but then plateaued by 72 hr. Conversely, R1441C and A1442P mutant expression attained 85% and 74% of WT levels at 24 hr but fell to 68% and 55% of WT levels by 72 hr, respectively. We found that proteasome inhibition markedly increased mutant LRRK2 to levels approaching those of WT. Taken together, our findings reveal increased intracellular degradation for both mutants. Furthermore, the impact of mutant and WT LRRK2 expression on HEK293 cell viability was assessed under normative and oxidative (hydrogen peroxide) conditions and found not to differ. Expression of WT and mutant LRRK2 protein gave rise to intracellular aggregates of similar appearance and cellular localization. In summary, we provide evidence that the novel A1442P mutant and the previously investigated R1441C pathogenic mutant exhibit increased intracellular degradation, a property reportedly demonstrated for the pathogenic LRRK2 kinase domain mutant I2020T. © 2013 Wiley Periodicals, Inc.     

Enhanced Recovery After Bariatric Surgery (ERABS): Clinical Outcomes from a Tertiary Referral Bariatric Centre

There is paucity of data on Enhanced Recovery After Bariatric Surgery (ERABS) protocols. This feasibility study reports outcomes of this protocol utilized within a tertiary-referral bariatric centre. Data on consecutive primary procedures (laparoscopic gastric bypasses, sleeve gastrectomies and gastric bands) performed over 9 months within an ERABS protocol were prospectively recorded. Interventions utilized included shortened preoperative fasts, intra-operative humidification, early mobilization and feeding, avoidance of fluid overload, incentive spirometry, use of prokinetics and laxatives. Data collected included demographics, co-morbidities, morbidity, mortality, length of stay (LOS) and re-admissions. A total of 226 procedures (age [mean ± SD], 45?±?11 years, median [interquartile range] BMI 44.9 [41.0–49.0] kg/m²) were undertaken: 150 (66 %) bypasses, 47 (21 %) sleeves and 29 (13 %) bands. Hypertension, diabetes mellitus, sleep apnea and limited mobility were present in 40 %, 34 %, 24 % and 9 % of patients, respectively. No anastomotic or staple line leaks/bleeds were encountered. Ten (4.4 %) patients developed postoperative morbidity (mainly respiratory complications). One death occurred from massive pulmonary embolus in a high-risk patient (despite insertion of preoperative-IVC filter). Respective mean ± SD LOS for bypasses, sleeves and bands were 1.88?±?1.12, 2.30?±?1.69 and 0.69?±?0.81 days. Successful discharge on the first postoperative day was achieved in 37 % and 28 % of bypasses and sleeves, respectively. Day-case gastric bands were performed in 48 %. Thirty-day hospital re-admission occurred in six (2.7 %) patients. Applying an ERABS protocol was feasible, safe, associated with low morbidity, acceptable LOS and low 30-day re-admission rates. The presence of multiple medical co-morbidities should not preclude use of an ERABS protocol within bariatric patients.     

Incidence of female urethral diverticulum: a population-based analysis and literature review

Introduction and hypothesis

Urethral diverticulum (UD) is a protrusion of the urethra through the periurethral fascia. We aimed to determine the population-based incidence of female UD.

Methods

Using the records-linkage system of the Rochester Epidemiology Project (REP), we identified women 18 years and older with a new diagnosis of UD in Olmsted County, Minnesota, USA, from 1 January 1980, through 31 December 2011. We also identified cases meeting the same criteria diagnosed at Mayo Clinic, regardless of county of residency. Incidence rates were calculated and trends for changes in incidence over time were tested. We conducted a systematic search of the MEDLINE, EMBASE, Cochrane Systematic Reviews, CENTRAL, Web of Science, and Scopus databases from inception through 30 March 2013, to identify published reports of UD incidence or prevalence.

Results

We identified 164 incidence cases, including 26 women residing in Olmsted County. Age-adjusted annual incidence of UD in Olmsted County was 17.9 per 1,000,000 women (<0.02 %) per year (95 % CI, 10.9–24.9). We observed a trend toward increased incidence during the past 3 decades (P?=?0.03). In our literature review, only 7 studies included an estimate of incidence or prevalence of UD; these estimates ranged from 6.4 per 1,000,000 per year (<0.01 %) having surgical intervention related to UD to a 4.7 % rate of UD diagnosed in asymptomatic women admitted for gynecological or obstetric issues.

Conclusions

In this population-based study, female UD was a rare disease, affecting fewer than 20 per 1,000,000 women (<0.02 %) per year.     

Satisfaction levels of paediatric surgeons in Canada

BACKGROUND:

Surgeons’ satisfaction levels may affect patient care and the stability of the surgical workforce.

METHODS:

A detailed Internet-based satisfaction survey was administered to paediatric surgeons in Canada in 2005 and 2012. Satisfaction was rated 1 (most) to 5 (least), in five areas: quality of life, financial compensation, work environment, academics and patient care.

RESULTS:

Responses were received from 21 surgeons in 2005 and 61 in 2012, representing 43% and 98% of practicing paediatric surgeons in Canada, respectively. Satisfaction levels were generally moderate to high in most areas during both years. In academics, surgeons were more satisfied in 2012 with the amount of teaching they provided (1.8 versus 2.2; P=0.02), and clinical research they performed (2.5 versus 3.0; P=0.04). In patient care, there was higher satisfaction with the ability to provide elective services without impediment (2.5 versus 3.0; P=0.02). Over the seven-year period, surgeons increasingly preferred the Canadian health care system over that of the United States (1.7 versus 2.2; P=0.02). In the 2012 survey, no differences in levels of satisfaction were found between male and female surgeons.

CONCLUSIONS:

During the recent seven-year period, satisfaction levels of paediatric surgeons in Canada have been stable with regard to quality of life, compensation and work environment, and improving in areas of academics and patient care. Male and female surgeons are equally satisfied. The Canadian health care system is preferred over that of the United States.     

Phosphorylated cellulose paper as highly efficient adsorbent for cadmium heavy metal ion removal in aqueous solutions

In search for more effective and eco-friendly adsorbent materials, this study comprehensively investigated Cd²⁺ adsorption onto phosphorylated cellulose paper (PCP). For this, cellulose microfibers (CMF) was extracted from Alfa fibers and phosphorylated using the solid-state phosphorylation approach. Then, the prepared PCP samples were characterized by SEM, EDX, XRD, FTIR, TGA, conductometric titration and zeta potential measurement. The adsorption of cadmium ions, the effect of time, pH and Cd²⁺ initial concentration were systematically studied in batch experiments. Based on the results, the highest adsorption capacity achieved was 479 mg of Cd²⁺ per g of PCP, which was remarkable compared to other modified cellulose capacities cited in the literature. Furthermore, the Cd²⁺ removal mechanism was investigated based on characterization results before and after adsorption and also based on the kinetics results. It was concluded that cation exchange and electrostatic attraction between phosphorylated cellulose and the cadmium ion mainly dominated the adsorption process. These findings highlighted that the phosphorylated cellulose paper has a broad application prospect in removal of divalent metal from aquatic solution.

In search for more effective and eco-friendly adsorbent materials, this study comprehensively investigated Cd²⁺ adsorption onto phosphorylated cellulose paper (PCP).