Practical Guidelines for the Surgical Treatment of Gallbladder Cancer

At present, surgical treatment is the only curative option for gallbladder (GB) cancer. Many efforts therefore have been made to improve resectability and the survival rate. However, GB cancer has a low incidence, and no randomized, controlled trials have been conducted to establish the optimal treatment modalities. The present guidelines include recent recommendations based on current understanding and highlight controversial issues that require further research. For T1a GB cancer, the optimal treatment modality is simple cholecystectomy, which can be carried out as either a laparotomy or a laparoscopic surgery. For T1b GB cancer, either simple or an extended cholecystectomy is appropriate. An extended cholecystectomy is generally recommended for patients with GB cancer at stage T2 or above. In extended cholecystectomy, a wedge resection of the GB bed or a segmentectomy IVb/V can be performed and the optimal extent of lymph node dissection should include the cystic duct lymph node, the common bile duct lymph node, the lymph nodes around the hepatoduodenal ligament (the hepatic artery and portal vein lymph nodes), and the posterior superior pancreaticoduodenal lymph node. Depending on patient status and disease severity, surgeons may decide to perform palliative surgeries.

Graphical Abstract

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Exotic and indigenous problem plants species used,by the Bapedi,to treat sexually transmitted infections in Limpopo Province,South Africa

Background

The ethnic usage of exotics and indigenous problem plants is a highly debated topic, as legislative requirements over-shadow their potential medicinal value, particularly to treat sexually transmitted infections (STIs). Limited information exists regarding their medicinal value among the Bapedi.

Objectives

To ascertain the importance of exotics and indigenous problem plants in the treatment of STIs, a major global primary health care challenge.

Methods

A field observation and semi-structured questionnaire focussing on species diversity, types of STIs treated and medicinal preparation as well as application was used to collect data from 34 traditional healers.

Results

Seven exotics and three indigenous problem species were identified. These species were used to treat four STIs; with Catharanthus roseus illustrating its dominance in the treatment of gonorrhoea. Some medicinal species used by Bapedi traditional healers have been validated through scientific research or through their extensive use by various cultures in South Africa and other parts of Africa. To the best of our knowledge Alternanthera pungens, Caesalpinia decapetala, Cinnamomum verum, and Citrullus lanatus are reported for the first time in the treatment of the investigated STIs.

Conclusions

Exotic and indigenous problem species constitute an important component of the STIs treatment protocol. Their utilization by Bapedi cautions against the narrow-minded approach of indiscriminate eradication, as these species can play a significant role in the primary health care needs of socio-economic vulnerable people.     

The Actin‐Binding Protein Cofilin and Its Interaction With Cortactin Are Required for Podosome Patterning in Osteoclasts and Bone Resorption In Vivo and In Vitro

The adhesion of osteoclasts (OCs) to bone and bone resorption require the assembly of specific F‐actin adhesion structures, the podosomes, and their dense packing into a sealing zone. The OC‐specific formation of the sealing zone requires the interaction of microtubule (MT) + ends with podosomes. Here, we deleted cofilin, a cortactin (CTTN)‐ and actin‐binding protein highly expressed in OCs, to determine if it acts downstream of the MT‐CTTN axis to regulate actin polymerization in podosomes. Conditional deletion of cofilin in OCs in mice, driven by the cathepsin K promoter (Ctsk‐Cre), impaired bone resorption in vivo, increasing bone density. In vitro, OCs were not able to organize podosomes into peripheral belts. The MT network was disorganized, MT stability was decreased, and cell migration impaired. Active cofilin stabilizes MTs and allows podosome belt formation, whereas MT disruption deactivates cofilin via phosphorylation. Cofilin interacts with CTTN in podosomes and phosphorylation of either protein disrupts this interaction, which is critical for belt stabilization and for the maintenance of MT dynamic instability. Accordingly, active cofilin was required to rescue the OC cytoskeletal phenotype in vitro. These findings suggest that the patterning of podosomes into a sealing zone involves the dynamic interaction between cofilin, CTTN, and the MTs + ends. This interaction is critical for the functional organization of OCs and for bone resorption. © 2016 American Society for Bone and Mineral Research.     

The DE loop of the domain III of the envelope protein appears to be associated with West Nile virus neutralization

The envelope (E) protein of WNV plays an important role in the virus neutralization. Using a mAb 5E8, a neutralizing epitope on the domain III of the E of the New York strain of WN virus was characterized. Results from neutralization-escape mutants and site-directed mutagenesis revealed that the 5E8 epitope is a highly conformation dependent epitope consisting of at least residues E330, E332 and E367 on the domain III. Besides known critical neutralizing epitopes E330 and E332, our results indicate that residue E367, a component of DE loop on the domain III, appeared to be associated with neutralization but little with neuroinvasion of the virus, as reported previously (Beasley et al., 2002).     

Unintended consequences of policy change to watchful waiting for asymptomatic inguinal hernias

Introduction

In 2009 the Department of Health instructed McKinsey & Company to provide advice on how commissioners might achieve world class National Health Service productivity. Asymptomatic inguinal hernia repair was identified as a potentially cosmetic procedure, with limited clinical benefit. The Birmingham and Solihull primary care trust cluster introduced a policy of watchful waiting for asymptomatic inguinal hernia, which was implemented across the health economy in December 2010. This retrospective cohort study aimed to examine the effect of a change in clinical commissioning policy concerning elective surgical repair of asymptomatic inguinal hernias.

Methods

A total of 1,032 patients undergoing inguinal hernia repair in the 16 months after the policy change were compared with 978 patients in the 16 months before. The main outcome measure was relative proportion of emergency repair in groups before and after the policy change. Multivariate binary logistic regression was used to adjust the main outcome for age, sex and hernia type.

Results

The period after the policy change was associated with 59% higher odds of emergency repair (3.6% vs 5.5%, adjusted odds ratio [OR]: 1.59, 95% confidence interval [CI]: 1.03–2.47). In turn, emergency repair was associated with higher odds of adverse events (4.7% vs 18.5%, adjusted OR: 3.68, 95% CI: 2.04–6.63) and mortality (0.1% vs 5.4%, p<0.001, Fisher’s exact test).

Conclusions

Introduction of a watchful waiting policy for asymptomatic inguinal hernias was associated with a significant increase in need for emergency repair, which was in turn associated with an increased risk of adverse events. Current policies may be placing patients at risk.     

Anti-arthritis effects of (E)-2,4-bis(p-hydroxyphenyl)- 2-butenal are mediated by inhibition of the STAT3 pathway

Background and Purpose

Products of Maillard reactions between aminoacids and reducing sugars are known to have anti-inflammatory properties. Here we have assessed the anti-arthritis effects of (E)-2,4-bis(p-hydroxyphenyl)-2-butenal and its possible mechanisms of action.

Experimental Approach

We used cultures of LPS-activated macrophages (RAW264.7 cells) and human synoviocytes from patients with rheumatoid arthritis for in vitro assays and the collagen-induced arthritis model in mice. NO generation, iNOS and COX2 expression, and NF-κB/IKK and STAT3 activities were measured in vitro and in joint tissues of arthritic mice, along with clinical scores and histopathological assessments. Binding of (E)-2,4-bis(p-hydroxyphenyl)-2-butenal to STAT3 was evaluated by a pull-down assay and its binding site was predicted using molecular docking studies with Autodock VINA.

Key Results

(E)-2,4-bis(p-hydroxyphenyl)-2-butenal (2.5–10 μg·mL⁻¹) inhibited LPS-inducedNO generation, iNOS and COX2 expression, and NF-κB/IKK and STAT3 activities in macrophage and human synoviocytes. This compound also suppressedcollagen-induced arthritic responses in mice by inhibiting expression of iNOS and COX2, and NF-κB/IKK and STAT3 activities; it also reduced bone destruction and fibrosis in joint tissues. A pull-down assay showed that (E)-2,4-bis(p-hydroxyphenyl)-2-butenal interfered with binding of ATP to STAT3. Docking studies suggested that (E)-2,4-bis(p-hydroxyphenyl)-2-butenal bound to the DNA-binding interface of STAT3 possibly inhibiting ATP binding to STAT3 in an allosteric manner.

Conclusions and Implications

(E)-2,4-bis(p-hydroxyphenyl)-2-butenal exerted anti-inflammatory and anti-arthritic effects through inhibition of the NF-κB/STAT3 pathway by direct binding to STAT3. This compound could be a useful agent for the treatment of arthritic disease.     

Serum cholesterol in idiopathic and lupus-related protein-losing enteropathy

Abstract The characteristics of protein-losing enteropathy were evaluated in patients with systemic lupus erythematosus. Among the patients with systemic lupus erythematosus (n=380) in a tertiary hospital, we reviewed the records of seven patients with generalized edema, hypoalbuminemia without proteinuria and positive results on 99mTc-labelled human serum albumin scintigrams. Patient characteristics and laboratory findings were compared between these seven patients and patients with lupus enteritis (n=15) or idiopathic protein-losing enteropathy (n=11). Compared with the lupus enteritis patients, the erythrocyte sedimentation rate and serum total cholesterol levels were significantly increased in patients with systemic lupus erythematosus-related protein-losing enteropathy. Compared with idiopathic protein-losing enteropathy patients, the level of serum total cholesterol was significantly increased, but the level of serum albumin was decreased in patients with systemic lupus erythematosus-related protein-losing enteropathy. Among patients with systemic lupus erythematosus-related protein-losing enteropathy, four patients had high serum total cholesterol levels (>or=248 mg/dL) and achieved complete remission after receiving high doses of steroid treatment. However, three patients who had low serum total cholesterol levels (相似文献