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.     

Electrospun Nanofibers Revisited: An Update on the Emerging Applications in Nanomedicine

Electrospinning (ES) has become a straightforward and customizable drug delivery technique for fabricating drug-loaded nanofibers (NFs) using various biodegradable and non-biodegradable polymers. One of NF’s pros is to provide a controlled drug release through managing the NF structure by changing the spinneret type and nature of the used polymer. Electrospun NFs are employed as implants in several applications including, cancer therapy, microbial infections, and regenerative medicine. These implants facilitate a unique local delivery of chemotherapy because of their high loading capability, wide surface area, and cost-effectiveness. Multi-drug combination, magnetic, thermal, and gene therapies are promising strategies for improving chemotherapeutic efficiency. In addition, implants are recognized as an effective antimicrobial drug delivery system overriding drawbacks of traditional antibiotic administration routes such as their bioavailability and dosage levels. Recently, a sophisticated strategy has emerged for wound healing by producing biomimetic nanofibrous materials with clinically relevant properties and desirable loading capability with regenerative agents. Electrospun NFs have proposed unique solutions, including pelvic organ prolapse treatment, viable alternatives to surgical operations, and dental tissue regeneration. Conventional ES setups include difficult-assembled mega-sized equipment producing bulky matrices with inadequate stability and storage. Lately, there has become an increasing need for portable ES devices using completely available off-shelf materials to yield highly-efficient NFs for dressing wounds and rapid hemostasis. This review covers recent updates on electrospun NFs in nanomedicine applications. ES of biopolymers and drugs is discussed regarding their current scope and future outlook.     

Effect of Isothermal Conditions on the Charge Trapping/Detrapping Parameters in e-Beam Irradiated Thermally Aged XLPE Insulation in SEM

The effect of isothermal conditions on the trapping/detrapping process of charges in e-beam irradiated thermally aged XLPE insulation in scanning electron microscopy (SEM) has been investigated. Different isothermal conditions ranging from room temperature to 120 °C are applied on both unaged and aged XLPE samples (2 mm thick) by a suitable arrangement associated with SEM. For each applied test temperature, leakage, and influence currents have been measured simultaneously during and after e-beam irradiation. Experimental results show a big difference between the fresh and aged material regarding trapping and detrapping behavior. It has been pointed out that in the unaged material deep traps govern the process, whereas the shallow traps take part in the aged one. Almost all obtained results reveal that the trapped charge decreases and then increases as the temperature increases for the unaged sample. A deflection temperature corresponding to a minimum is observed at 50 °C. However, for the aged material, the maximum trapped charge decreases continuously with increasing temperature, and the material seems to trap fewer charges under e-beam irradiation at high temperature. Furthermore, thermal aging leads to the occurrence of detrapping process at high temperatures even under e-beam irradiation, which explains the decrease with time evolution of trapped charge during this period. The recorded leakage current increases with increasing temperature for both cases with pronounced values for aged material. The effect of temperature and thermal aging on electrostatic influence factor (K) and total secondary electron emission yield (σ) were also studied.     

The impact of sarcopenia on the outcome of patients with cirrhosis with and without hepatocellular carcinoma who undergo liver transplantation

Background: The impact of sarcopenia on the outcome of patients with cirrhosis who undergo liver transplantation (LT) has been analysed in heterogeneous cohorts...     

Clinical trial considerations in sickle cell disease: patient-reported outcomes,data elements,and the stakeholder engagement framework

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