Pharmacologic inhibition of mTOR antagonizes the cytotoxic activity of pemetrexed in non-small cell lung cancer

Purpose  

Pemetrexed, an inhibitor of thymidylate synthase (TS) and additional folate-dependent enzymes, is clinically active in patients suffering from “non-squamous” non-small cell lung cancer (NSCLC). High expression of TS has been implied as biomarker predictive of resistance to pemetrexed. Against this background, we studied whether inhibition of mTOR could lower expression of TS and thus sensitize NSCLC cells to pemetrexed.     

Human papillomavirus and oral disease – emerging evidence: a review

Human papillomavirus (HPV) infections have received considerable attention in recent years. Of the 120 or so known types of the virus, some cause a variety of benign wart‐like lesions of the skin and genital and oral mucosae, whilst others are aetiologically associated with cervical and anogenital cancers. Recent epidemiologic evidence suggests that HPV may also be an independent risk factor for oropharyngeal cancer. In this context it has been suggested that HPV virus may modulate the process of carcinogenesis in some tobacco and alcohol induced oropharyngeal cancers and act as the primary oncogenic agent for inducing carcinogenesis among non‐smokers. Dental practitioners have a major role in detecting all lesions of the oral mucosa caused, or possibly caused, by HPV. This paper briefly reviews the current state of knowledge of molecular and clinical aspects of HPV infections of the oral mucosa.     

Comparision of blood loss between computer assisted and conventional total knee arthroplasty

Background:

Bleeding during total knee arthroplasty (TKA) can cause significant morbidity and mortality. One proposed benefit of computer assisted TKA is decreased bleeding as the femoral canal is not invaded. This study assessed blood loss between computer assisted surgery (CAS) and conventional TKA.

Materials and Methods:

73 consecutive patients (37 males, 36 females) underwent primary TKA between 2006 and 2009. Thirty eight patients underwent navigated TKA and 35 underwent conventional TKA for symptomatic osteoarthritis of the knee. These patients were matched for age, gender, and body mass index (BMI). Average age was 70.3 years (range 47-91 years). Mean BMI was 30 (range 17-49). Average preoperative hemoglobin was 13.26 g/dL (range 8.7-18.4 g/dL) in the navigated group and 13.47 g/dL (range 9.6-15.8 g/dL) in the conventional group (P = 0.9). Average tourniquet time was 110 min (range 90-150 min) in the navigated group and 96.7 min (range 60-145 min) in the conventional group (P = 0.77).

Results:

Average postoperative hemoglobin in the navigated group was 10.34 g/dL (range 7.5-14.8 g/dL) and in the conventional group was 10.03 g/dL (range 7.5-12.2 g/dL) (P = 0.17). Six patients in both groups required blood transfusions. The mean drain collection was 599 mL (range 150-1370 mL) in the navigated group and 562 mL (range 750-1000 mL) in the conventional group (P = 0.1724). These results suggest that there is no significant reduction in blood loss in CAS TKA.

Conclusion:

These results suggest that there is no significant difference in blood loss in CAS TKA and conventional TKA. This study also highlights the heterogeneity of methods used in studies related to CAS TKA. We believe that there is a need for a large multicenter prospective randomized controlled trial to be performed before a consensus can be reached on the influence of CAS techniques on blood loss during primary TKA.     

Wire fractures in Solysafe septal occluders: a single center experience

Objectives : To determine the incidence of device fractures (DF) after implantation of a Solysafe® Septal Occluder (iSSO) and to assess the spectrum of associated problems. Background : In August 2010, after initial unpublished reports on DF, the manufacturer issued an “urgent field safety notice,” prompting all medical care providers to re‐examine all patients after iSSO. Methods : Prospective single center study. Extended follow‐up examination, including standardized fluoroscopy (sF), was performed in all patients after iSSO. Results : A total of 111 patients had undergone iSSO at our institution between June 2005 and July 2010. Median age and body weight were 50 years (9.3–79.6) and 75 kg (29–122), respectively. Indications for iSSO were (1) patent foramen ovale in patients with a history of cryptogenic stroke (n = 84; 76%) and (2) hemodynamically significant atrial septal defect of the secundum type (n = 27; 24%). A total of 113 devices were implanted. Complete follow‐up was available in 103 patients (92.8%). Median follow‐up was 1.9 years (0–5.2). There were no postimplantation neurological events or symptoms. The closure rate was 97.1%. DF was suspected on a chest X‐ray in one patient and documented in 10 patients by sF. The overall probability of freedom from DF was 82.3% after 5 years. One patient had embolization of a device fragment to the right pulmonary artery. So far, all patients with DF have been managed conservatively. Conclusions : The incidence of DF after iSSO is unacceptably high. sF is imperative for accurate diagnosis of DF. Further, follow‐up is needed to determine the risk of clinical complications and to optimize management. © 2012 Wiley Periodicals, Inc.     

Spinocerebellar ataxia type 3/Machado–Joseph disease: segregation patterns and factors influencing instability of expanded CAG transmissions

Controversies about Mendelian segregation and CAG expansion (CAGexp) instabilities during meiosis in spinocerebellar ataxia type 3/Machado–Joseph disease (SCA3/MJD) need clarification. Additional evidence about these issues was obtained from the cohort of all SCA3/MJD individuals living in South Brazil. A survey was carried out to update information registered since 2001. Deaths were checked with the Public Information System, and data was made anonymous. Anticipation and delta‐CAGexp from parent–offspring pairs, and delta‐CAGexp between siblings were obtained. One hundred and fifty‐nine families (94% of the entire registry) were retrieved, comprising 3725 living individuals as of 2015, 625 of these being symptomatic. Minimal prevalence was 6:100,000. Carriers of a CAGexp represented 65.6% of sibs in the genotyped offspring (p < 0.001). Median instability was larger among paternal than maternal transmissions, and instabilities correlated with anticipation (r = 0.38; p = 0.001). Age of the parent correlated to delta‐CAGexp among 115 direct parent–offspring CAGexp transmissions (ρ = 0.23, p = 0.014). In 98 additional kindreds, the delta‐CAGexp between 269 siblings correlated with their delta‐of‐age (ρ = 0.27, p < 0.0001). SCA3/MJD was associated with a segregation distortion favoring the expanded allele in our cohort. Instability of expansion during meiosis was weakly influenced by the age of the transmitting parent at the time of conception.     

Men’s perspectives on women’s empowerment and intimate partner violence in rural Bangladesh

Intimate partner violence (IPV) may increase as women in patriarchal societies become empowered, implicitly or explicitly challenging prevailing gender norms. Prior evidence suggests an inverse U-shaped relationship between women’s empowerment and IPV, in which violence against women first increases and then decreases as more egalitarian gender norms gradually gain acceptance. By means of focus-group discussions and in-depth interviews with men in 10 Bangladeshi villages, this study explored men’s evolving views of women, gender norms and the legitimacy of men’s perpetration of IPV in the context of a gender transition. It examines men’s often-contradictory narratives about women’s empowerment and concomitant changes in norms of masculinity, and identifies aspects of women’s empowerment that are most likely to provoke a male backlash. Findings suggest that men’s growing acceptance of egalitarian gender norms and their self-reported decreased engagement in IPV are driven largely by pragmatic self-interest: their desire to improve their economic status and fear of negative consequences of IPV.