J. Clin. Med., Volume 7, Issue 6 (June 2018) – 41 articles

Prostate cancer (PCa) is a leading cause of mortality and morbidity globally. While genomic alterations have been identified in PCa, in contrast to some other cancers, use of such information to personalize treatment is still in its infancy. Here, we discuss how PAGE4, a protein which appears to act both as an oncogenic factor as well as a metastasis suppressor, is a novel therapeutic target for PCa. Inhibiting PAGE4 may be a viable strategy for low-risk PCa where it is highly upregulated. Conversely, PAGE4 expression is downregulated in metastatic PCa and, therefore, reinstituting its sustained expression may be a promising option to subvert or attenuate androgen-resistant PCa. Thus, fine-tuning the levels of PAGE4 may represent a novel approach for personalized medicine in PCa. Full article

Non-ulcer dyspepsia (NUD) is a term used to define a set of symptoms that are believed to originate from the gastroduodenal region, and no underlying organic, systemic, or metabolic reason can be found. The majority of patients suffer from chronic symptoms although half of the patients report improvement in symptoms with time. The potential role exocrine pancreatic insufficiency in NUD patients has not been clarified yet. We aimed to identify exocrine pancreas function with pancreatic fecal elastase-1 in patients diagnosed with non-ulcer dyspepsia and no typical exocrine pancreatic insufficiency (EPI) symptoms. Thirty-five patients referred to gastroenterology clinics with NUD and 35 people with no dyspeptic symptoms as a control group were included in this prospective study. Non-ulcer dyspepsia patients were classified as group 1 and control subjects classified as group 2. Upper gastrointestinal endoscopies were performed in both groups. Assessment of exocrine pancreatic function was performed by measuring fecal elastase-1 concentration with a commercial ELISA kit using polyclonal antibodies (BioServ Diagnostics) in NUD patients compared to control subjects. Mean fecal elastase-1 levels were significantly lower in group 1 patients compared with group 2 (367.47 ± 43.27; 502.48 ± 50.94 respectively; p = 0.04). The percentage of the patients with EPI was significantly higher in group 1 (p = 0.02). Patients with NUD should be re-evaluated if they do not show satisfactory improvement with treatment. Exocrine pancreatic insufficiency was significantly higher in patients with NUD in our study. Evaluation for the presence of EPI can be a cost effective approach in management of refractory patients during the process of ruling out organic reasons. Full article

Osteoporosis is a disease characterized by osteoclast-mediated low bone mass. The modulation of osteoclasts is important for the prevention or therapeutic treatment of loss of bone mass. Osteoclasts, which are bone-resorbing multinucleated cells, are differentiated from the hematopoietic stem cell monocyte/macrophage lineage by Receptor activator of nuclear factor kappa-B ligand (RANKL) expressed from osteoblasts and stromal cells. RANKL signaling ultimately activates nuclear factor of activated T Cells 1 (NFATc1), which is a master transcription factor in osteoclastogenesis. Betulin, a lupine type pentacyclic triterpenoid, was isolated from the bark of Betula platyphylla. Betulin inhibited RANKL-mediated osteoclast differentiation by downregulating NFATc1. Betulin may serve as a useful structural scaffold in the therapeutic agent development to prevention/treatment the osteoclast-mediated bone disorder. Full article

It is now widely established that management of lung cancer is much more complex and cannot be centered on the binary classification of small-cell versus non-small cell lung cancer (NSCLC). Lung cancer is now recognized as a highly heterogeneous disease that develops from genetic mutations and gene expression patterns, which initiate uncontrolled cellular growth, proliferation and progression, as well as immune evasion. Accurate biomarker assessment to determine the mutational status of driver mutations such as EGFR, ALK and ROS1, which can be targeted by specific tyrosine kinase inhibitors, is now essential for treatment decision making in advanced stage NSCLC and has shifted the treatment paradigm of NSCLC to more individualized therapy. Rapid advancements in immunotherapeutic approaches to NSCLC treatment have been paralleled by development of a range of potential predictive biomarkers that can enrich for patient response, including PD-L1 expression and tumor mutational burden. Here, we review the key biomarkers that help predict response to treatment options in NSCLC patients. Full article

Non-alcoholic steatosis is a common health problem worldwide due to altered food habits and life styles, and it is intimately linked with various metabolic disorders. In the present study, we investigated the molecular mechanism of Ganoderma lucidum (GL) against the development of non-alcoholic steatosis using in vivo and in vitro settings. C57BL/6 mice fed with normal diet (ND) or high fat diet (HFD) were administered GL extract or vehicle for 16 weeks. HFD feeding increased serum alanine aminotransferase level and hepatic lipid droplet, but these increases were significantly attenuated by GL. GL inhibited the increases in epididymal and perirenal adipose tissue weights and serum cholesterol and LDL levels in HFD-fed mice. Fasting blood glucose levels were elevated in HFD-fed mice compared to ND-fed mice, and glucose and insulin sensitivities were deteriorated. These changes were markedly improved by GL. GL restored the reduction of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) phosphorylation in the liver of HFD-fed mice, and increased AMPK and ACC phosphorylation in HepG2 and 3T3-L1 cells. GL induced GLUT4 protein expression in 3T3-L1 cells. Finally, GL attenuated lipid accumulation induced by free fatty acid in HepG2 cells. Taken together, our results indicate that GL has a potential to improve non-alcoholic steatosis and the associated complicated disorders via the induction of energy metabolizing enzymes. Full article

Immune checkpoint inhibitors have shown efficacy in the treatment of non-small cell lung cancer (NSCLC) in the adjuvant, first- and subsequent-line settings. In metastatic disease, they provide hope of durable response where “best-case” scenario has long been inadequate. This progress has highlighted the immunogenic nature of NSCLC and invigorated research into immunotherapy in the field. In this review we consider the foundations of immunotherapy in NSCLC, canvass the current research and summarise the evidence guiding clinical practice. Full article

Therapeutic doses of tedizolid phosphate, an oxazolidinone antibiotic, lack monoamine oxidase inhibition in vivo, potentially resulting in an improved safety profile versus other oxazolidinones. This randomized, double-blind, placebo-controlled, 2-period, 2-sequence, crossover, phase 1 study (NCT01577459) assessed the potential for pharmacokinetic (PK) interactions between tedizolid and pseudoephedrine. Eighteen healthy volunteers (age: 18–45 years) were block-randomized to 1 of 2 treatment sequences containing 2 treatment periods (tedizolid phosphate or placebo once daily for 4 days; single dose of pseudoephedrine 60 mg on day 5) separated by a 2-day washout. Median time to maximum plasma concentration for tedizolid and pseudoephedrine ranged from 3 to 4 h, regardless of treatment coadministration. Steady-state tedizolid had no effect on the PK of pseudoephedrine; geometric mean ratio and 90% confidence interval remained within the no-effect 0.8 to 1.25 boundaries. The maximum observed concentration of tedizolid decreased by approximately 14% when pseudoephedrine was coadministered; no changes in the area under the plasma concentration-time curve or the minimum observed plasma concentration occurred. All adverse events (AEs) were mild, and there were no serious AEs or study drug discontinuations. No meaningful PK interactions occurred between tedizolid and pseudoephedrine, and tedizolid was well tolerated when administered in conjunction with pseudoephedrine. Full article

Complementary Alternative Medicine (CAM) that targets infants and children can place them at grave risk. Our plan is to review some of the major cases of CAM used by parents, and by unlicensed and even licensed health professionals. Complications from CAM are rarely the focus of regulatory bodies, or even the courts. Even regulated health professionals, who have profited by misrepresenting science-based evidence for treatment or prevention of disease, have been rarely sanctioned by their respective Boards or Colleges. This must change. In addition, there is a dire need for regulators, including the governments, who allow quack products and devices to be marketed in their respective countries, to prosecute them. Existing regulations must be coupled with more effective enforcement. Some of these cases have had a direct connection to me personally, while others are examples of just plain dangerous quackery. Full article

Objective: To review the current published literature on the use of procalcitonin as a diagnostic and prognostic marker in adult patients with meningitis. Methods: We conducted a PubMed search to identify all relevant publications regarding the diagnostic and prognostic value of serum procalcitonin in patients with a known or suspected central nervous system infection. We also reviewed the bibliographies of all identified manuscripts in an attempt to identify additional relevant references. Results: A significant body of evidence suggests that serum procalcitonin has a promising role and can be a useful biomarker in the assessment of patients with meningitis. Conclusions: Our literature review suggests that data on the role of Cerebrospinal Fluid (CSF) procalcitonin are limited, whereas serum procalcitonin (S–PCT) is probably a useful tool in the evaluation of patients with a known or suspected central nervous system infection and can help distinguish between bacterial and viral meningitis. Full article

We evaluated the effects of exercise on proactive memory interference. Study 1 (n = 88) employed a 15-min treadmill walking protocol, while Study 2 (n = 88) included a 15-min bout of progressive maximal exertion treadmill exercise. Each study included four distinct groups, in which groups of 22 participants each were randomly assigned to: (a) exercise before memory encoding, (b) a control group with no exercise, (c) exercise during memory encoding, and (d) exercise after memory encoding (i.e., during memory consolidation). We used the Rey Auditory Verbal Learning Test (RAVLT) to assess proactive memory interference. In both studies, the group that exercised prior to memory encoding recalled the most words from list B (distractor list) of the RAVLT, though group differences were not statistically significant for Study 1 (walking exercise) (p = 0.521) or Study 2 (high-intensity exercise) (p = 0.068). In this sample of young adults, high intensity exercise prior to memory encoding showed a non-significant tendency to attenuate impairments in recall attributable to proactive memory interference. Thus, future work with larger samples is needed to clarify potential beneficial effects of exercise for reducing proactive memory interference. Full article

The present experiment evaluated the effects of acute exercise on iconic memory and short- and long-term episodic memory. A two-arm, parallel-group randomized experiment was employed (n = 20 per group; M_age = 21 year). The experimental group engaged in an acute bout of moderate-intensity treadmill exercise for 15 min, while the control group engaged in a seated, time-matched computer task. Afterwards, the participants engaged in a paragraph-level episodic memory task (20 min delay and 24 h delay recall) as well as an iconic memory task, which involved 10 trials (at various speeds from 100 ms to 800 ms) of recalling letters from a 3 × 3 array matrix. For iconic memory, there was a significant main effect for time (F = 42.9, p < 0.001, η²_p = 0.53) and a trend towards a group × time interaction (F = 2.90, p = 0.09, η²_p = 0.07), but no main effect for group (F = 0.82, p = 0.37, η²_p = 0.02). The experimental group had higher episodic memory scores at both the baseline (19.22 vs. 17.20) and follow-up (18.15 vs. 15.77), but these results were not statistically significant. These findings provide some suggestive evidence hinting towards an iconic memory and episodic benefit from acute exercise engagement. Full article

Background: Ultrasound measurement of dynamic changes in inferior vena cava (IVC) diameter and collapsibility index (CI) are used to estimate the fluid responsiveness and intravascular volume status. We conducted an analysis to quantify the sonographic measurement of IVC diameter changes in adult patients at the preoperative and postoperative periods. Methods: Ultrasonography was performed on 72 patients scheduled for surgery with American Society of Anesthesiologists physical status I to III. Quantitative assessments of the end-expiration (D_min), end-inspiration (D_max), and CI at preoperative and postoperative period were compared in a prospective, observational study. The patients received intravenous fluid according to standard protocol regimes peroperatively. Results: Ultrasonography of IVC measurement was unsuccessful in 12.5% of patients and 63 patients remained for analyses. The mean age was 43.29 ± 17.22 (range 18–86) years. The average diameter of the D_min, D_max, and dIVC preoperative and postoperative were 1.99 ± 0.31 vs. 2.05 ± 0.29 cm, 1.72 ± 0.33 vs. 1.74 ± 0.32 cm, 14.0 ± 9.60% vs. 15.14 ± 11.18%, respectively (p > 0.05). CI was positively associated preoperatively and postoperatively (regression coefficient = 0.438, p < 0.01). Conclusion: The diameter of the IVC did not change preoperatively and postoperatively in adult patients with standard fluid regimens. The parameters of the IVC diameter increased postoperatively according to the preoperative period. Full article

Recent changes in lung cancer care, including new approvals in first line and the introduction of high-throughput molecular technologies in routine testing led us to question ourselves on how deeper molecular testing may be helpful for the optimal use of targeted drugs. In this article, we review recent results in the scope of personalized medicine in lung cancer. We discuss biomarkers that have a therapeutic predictive value in lung cancer with a focus on recent changes and on the clinical value of large scale sequencing strategies. We review the use of second- and third-generation EGFR and ALK inhibitors with a focus on secondary resistance alterations. We discuss anti-BRAF and anti-MEK combo, emerging biomarkers as NRG1 and NTRKs fusions and immunotherapy. Finally, we discuss the different technical issues of comprehensive molecular profiling and show how large screenings might refine the prediction value of individual markers. Based on a review of recent publications (2012–2018), we address promising approaches for the treatment of patients with lung cancers and the technical challenges associated with the identification of new predictive markers. Full article

Background: The present study investigated the effectiveness of platelet-rich plasma (PRP) and mesenchymal stem cells (MSCs) in wound healing suppressed by corticosteroid in rats. Methods: Forty rats were separated into four groups. To disrupt the wound-healing processes, intraperitoneal single dose 10 mg/kg methylprednisolone was administered to all rats with the exception of Sham-S group. Then, full-thickness incision was performed to the abdominal skin of all animals, and PRP or MSCs were applied to the incision line except the Sham-S and Sham-M group animals. Ten days later, all animals were sacrificed to investigate: tissue collagenization, inflammation, and re-epithelialization grades histopathologically; and tissue hydroxyproline (HP), interleukin-1β (IL-1β), tumor necrosis factor-α levels biochemically. Results: Collagenization (p = 0.003) and inflammation grade (p = 0.002) values were higher in PR group. Tissue HP level value was found to be high in MC group (p < 0.001). Tissue IL-1β level value of Sham-M group was lower than those of other groups (p < 0.001). Conclusions: This preliminary study revealed that PRP could improve the histopathological grades in wound healing which was suppressed by corticosteroid in rats, while MSCs could show their therapeutic effects via biochemical route. These positive effects were more salient in PR group. Full article

Data evaluating the presence and characteristics of mesenteric lymph nodes (LNs) in patients with ulcerative colitis (UC) are scarce. The aim of this study is to determine the presence and characteristics of LNs in UC. The LN characteristics in computed tomography (CT), including LN dimension and attenuation, were evaluated retrospectively in 100 patients with UC (61 active and 39 inactive cases). Clinical characteristics and laboratory parameters, including CBC, biochemical analysis, erythrocyte sedimentation rate (ESR), and C reactive protein (CRP) were also compared. Mesenteric LNs were evident in all patients with UC. The attenuation and dimension of mesenteric LNs did not differ between active and inactive patients with UC. No correlation was found among patients with UC in terms of LN dimension, attenuation, ESR, CRP, leucocyte, and albumin (all with p > 0.05). The current study suggested that inflammation results in the development of mesenteric LN in UC, similar to Crohn’s disease and other inflammatory disorders. Full article

Aims: The PR domain containing 16 (PRDM16) gene and the Phosphodiesterase 4D (PDE4) gene are both an essential regulators in the thermogenesis process in the brown adipose tissues (BAT). The influence of polymorphisms in those genes on obesity and blood lipids profile is unknown particularly in the Saudi population, so the current study is aiming to explore that. Methods: A case control format was used that involved 89 obese individual and 84 non-obese (control). The PRDM16 (rs2651899) and PDE4D (rs295978) polymorphisms were genotyped using KASP™ (Competitive Allele-Specific PCR) method. Results: The distributions of the AA, GG, and AG genotypes of PRDM16 (rs2651899) polymorphism were 0.19, 0.26 and 0.54, respectively. While the distribution of the mutated allele A was 0.7 in the obese group comparing to 0.34 in the non-obese group. Participants with the mutated genotypes, AA and AG, of PRDM16 (rs2651899) polymorphism were significantly more likely to be obese as compared to participants with wild type genotype (OR = 21, 95% CI = 5.4190 to 84.4231, p value < 0.0001 and OR = 44.6, 95% CI = 11.5984 to 172.0157, p value < 0.0001, respectively). The wild type GG genotype of this polymorphism was associated with higher blood cholesterol, HDL and LDL but lower blood triglyceride compared with the mutated genotypes (p = 0.003, p = 0.008, p = 0.02 and p = 0.003, respectively). In contrast, PDE4D (rs295978) polymorphism was not associated with risk of obesity and had no effects on blood lipids profile. Conclusions: We found that the PRDM16 polymorphism (rs2651899) is a risk factor for obesity and influence blood lipids profiles significantly in Saudi population. While the PDE4D (rs295978) polymorphism didn’t show significant effect on risk of obesity or blood lipids profiles. Full article

Physical activity (PA) among breast cancer survivors (BCS) can improve this population’s health and quality of life (QoL). This study evaluated the effectiveness of a combined smartwatch- and social media-based health education intervention on BCS’s health outcomes. Thirty BCS ( $\overline{\mathrm{X}}$ _age = 52.6 ± 9.3 years; $\overline{\mathrm{X}}$ _Wt = 80.2 ± 19.6 kg) participated in this 10-week, 2-arm randomized trial, with BCS randomized into: (1) experimental group (n = 16): received Polar M400 smartwatches for daily PA tracking and joined a Facebook group wherein Social Cognitive Theory-related PA tips were provided twice weekly; and (2) comparison group (n = 14): only joined separate, but content-identical Facebook group. Outcomes included PA, physiological, psychosocial, and QoL variables. Specifically, PA and energy expenditure (EE) was assessed by ActiGraph GT3X+ accelerometers while physiological, psychosocial, and QoL were examined via validated instruments at baseline and post-intervention. No baseline group differences were observed for any variable. Ten BCS dropped out of the study (experimental: 4; comparison: 6). Compared to completers, dropouts differed significantly on several outcomes. Thus, a per-protocol analysis was performed, revealing significant group differences for changes in social support (t = −2.1, p = 0.05) and barriers (t = −2.2, p = 0.04). Interestingly, the comparison group demonstrated improvements for both variables while the intervention group demonstrated slightly decreased social support and no change in barriers. Notably, both groups demonstrated similarly increased daily light PA, moderate-to-vigorous PA, EE, and steps of 7.7 min, 5.1 min, 25.1 kcals, and 339 steps, respectively, over time. Despite extensive user training, several experimental BCS found the Polar M400 use difficult—possibly decreasing intervention adherence. Future interventions should utilize simpler smartwatches to promote PA among middle-aged clinical/non-clinical populations. Full article

High-sensitivity C-reactive protein (hsCRP) is a prognostic factor for hepatocellular carcinoma (HCC), while albumin is known to be a disease severity index of the malnutrition status in HCC patients. The present study investigated the association between postoperative hsCRP/albumin ratio and both overall survival (OS) and recurrence-free survival (RFS) following HCC surgery. This retrospective observational study examined the medical records of 389 patients who underwent resection for HCC between 2004 and 2013. Postoperative day 0–1 hsCRP/albumin ratio was collected, and the optimal postoperative mortality cut-off point was derived using receiver operating characteristics (ROC) analysis. A postoperative hsCRP/albumin ratio increase of 1.0 was associated with a 1.171-fold increase in mortality (hazard ratio (HR): 1.171, 95% confidence interval (CI): 1.072–1.278, p < 0.001) and a 1.19-fold increase in recurrence (HR: 1.190, 95% CI: 1.108–1.278, p < 0.001). The hsCRP/albumin ratio cut-off point was found to be 0.625 and 0.500. When patients were grouped by this cut-off point, the >0.625 group showed a 2.257-fold increase in mortality (HR: 2.257, 95% CI: 1.470–3.466, p < 0.001), and the >0.500 group showed a 1.518-fold increase in recurrence (HR: 1.518, 95% CI: 1.125–2.050, p = 0.006). Full article

It is not sufficiently known that frequentist statistics cannot provide direct information on the probability that the research hypothesis tested is correct. The error resulting from this misunderstanding is compounded when the hypotheses under scrutiny have precarious scientific bases, which, generally, those of complementary alternative medicine (CAM) are. In such cases, it is mandatory to use inferential statistics, considering the prior probability that the hypothesis tested is true, such as the Bayesian statistics. The authors show that, under such circumstances, no real statistical significance can be achieved in CAM clinical trials. In this respect, CAM trials involving human material are also hardly defensible from an ethical viewpoint. Full article

In the past, numerous non-operative treatments for adolescent idiopathic scoliosis (AIS), including exercise, physical therapy, electrical stimulation, and brace treatment, have been tried to delay or prevent the curve progression. Of these, brace treatment is the only option that is widely accepted and has demonstrated the efficacy to alter the natural history of AIS. Recently, the importance of brace treatment for AIS has been increasing since the efficacy was objectively established by the BrAIST (Bracing in Adolescent Idiopathic Scoliosis Trial) study in 2013. This editorial article summarizes the current status of brace treatment in patients with AIS and discusses future prospects on the basis of our clinical experiences. Full article

This multidisciplinary series is aimed at offering readers many opportunities to appreciate how a clinical and ethical approach to pregnancy has changed in patients with kidney diseases and with related conditions, including diabetes, hypertension, and immunologic diseases. Furthermore, this series aims to focus on the fact that many issues remain unreslved, that there are enormous gaps in knowledge, and that the bioethical approach needs to integrated in the clinical practice, which would allow for a deeper appreciation of different cultural and religious backgrounds. Much still needs to be done to allow women suffering from all stages of chronic kidney disease (CKD) and those with predisposed conditions, so that they may experience safe pregnancies, starting from an increased awareness of the importance of CKD, even in its early stages, to the detection of risk factors. Women who have experienced preeclampsia or acute kidney injury in pregnancy need to have follow-up checks. The role of urinary infections, kidney stones, and urinary malformations is not fully acknowledged, nor have univocal control schedules and treatment schemas yet been defined for the different kidney diseases. In this regard, the fight for equitable treatment for all women with acute or chronic kidney disease in pregnancy and for the widespread prevention of adverse pregnancy-related and long-term outcomes is ultimately a battle for equitable healthcare. Full article

Introduction: Epilepsy is one of the most frequently diagnosed chronic neurological disorders in children. Diagnosis is often based on seizure history and electroencephalography (EEG) assessment. Magnetic resonance imaging (MRI) is recommended for etiologic workup and intervention requirements. We aimed to detect by MRI if focal structural abnormalities are present in the brain in relation to interictal epileptiform discharges (IED). Material and Methods: The study was designed retrospectively. The data were collected from patients admitted to Near East University, Department of Pediatric Neurology, who were aged between 3 months and 18 years and who were diagnosed with epilepsy. The cases considered in the current study, however, were patients that had an EEG record prior to initiating treatment and an MRI within the first six months following diagnosis. Results: Among 222 patients, 212 (95.5%) had IED, and 92 (41.4%) had abnormal MRI results. The most frequently seen abnormalities detected by MRI were encephalomalacia, hydrocephaly, and atrophy. Among patients who had IED, the ones with multifocal IED were documented to have a statistically significant higher rate of abnormalities in MRI scans. In other patients, IED had no significant correlation with structural lesions detected by MRI. Conclusion: IED can be unrelated to MRI findings. Focal IED were not statistically concordant with the structural lesions detected by MRI. However, for the cases with multifocal discharges revealed by interictal EEG, the rate of abnormalities detected using MRI was 68%. Therefore, the likelihood of detecting abnormalities using MRI in patients with multifocal IED does support the necessity of the use of MRI in early diagnosis stages. Full article

Population-based estimates are lacking for the temporal trends in the contralateral breast cancer (CBC) risk for patients with breast cancer (BC). Data for BC patients diagnosed with CBC were collected from the Surveillance, Epidemiology, and End Results database. CBC incidence was calculated using the Kaplan-Meier method and the temporal trend in CBC incidence was assessed using joinpoint regression. Survival analysis was calculated using propensity scoring (PS) and multivariate Cox regression with a competing risk model. We found that 10,944 of 212,630 patients with early-stage BC were subsequently diagnosed with secondary BC in the contralateral breast. The 5-, 10-, 15-, and 20-year cumulative CBC incidences were 1.9, 4.6, 7.6, and 10.5%, respectively. Being younger (<40 years), black, hormone receptor-negative, and having undergone radiotherapy were correlated with a high risk of CBC occurrence. CBC incidence increased continuously in the first 11 years after the initial cancer diagnosis, and the upward trend slowed from years 11 to 21, and tended to decline from years 21 to 24. CBC diagnosis was significantly and negatively associated with survival. We reported population-based estimates of the CBC occurrence pattern and risk factors. Patients are at high risk of developing CBC in the first 21 years after the initial BC diagnosis. Full article

There is evidence to suggest that biological sex plays a critical role in memory function, with sex differentially influencing memory type. In this review, we detail the current evidence evaluating sex-specific effects on various memory types. We also discuss potential mechanisms that explain these sex-specific effects, which include sex differences in neuroanatomy, neurochemical differences, biological differences, and cognitive and affect-related differences. Central to this review, we also highlight that, despite the established sex differences in memory, there is little work directly comparing whether males and females have a differential exercise-induced effect on memory function. As discussed herein, such a differential effect is plausible given the clear sex-specific effects on memory, exercise response, and molecular mediators of memory. We emphasize that future work should be carefully powered to detect sex differences. Future research should also examine these potential exercise-related sex-specific effects for various memory types and exercise intensities and modalities. This will help enhance our understanding of whether sex indeed moderates the effects of exercise and memory function, and as such, will improve our understanding of whether sex-specific, memory-enhancing interventions should be developed, implemented, and evaluated. Full article

The purpose of this study was to evaluate the value of diffusion-weighted MRI (DW-MRI) in differentiating benign and malignant head and neck masses by comparing their apparent diffusion coefficient (ADC) values. The study included 32 patients with a neck mass >1 cm in diameter who were examined with echo planar DW-MRI. Two different diffusion gradients (b values of b = 0 and b = 1000 s/mm²) were applied. DWI and ADC maps of 32 neck masses in 32 patients were obtained. Mean ADC values of benign and malignant neck lesions were measured and compared statistically. A total of 15 (46.9%) malignant masses and 17 (53.1%) benign masses were determined. Of all the neck masses, the ADC value of cystic masses was the highest and that of lymphomas was the lowest. The mean ADC values of benign and malignant neck masses were 1.57 × 10⁻³ mm²/s and 0.90 × 10⁻³ mm²/s, respectively. The difference between mean ADC values of benign and malignant neck masses was significant (p < 0.01). Diffusion-weighted MRI with ADC measurements can be useful in the differential diagnosis of neck masses. Full article

Introduction: Around 3–5% of non-small cell lung cancers (NSCLC) are ALK-positive. Crizotinib was the first approved ALK inhibitor from clinical trials. However, there are less data on the utilization and patient outcomes associated with crizotinib in real-world clinical practice. Methods: This was a retrospective, observational study of adult crizotinib-treated ALK-positive metastatic NSCLC patients who received treatment between 1 September 2011 and 31 October 2014, with follow up through 31 December 2015. Data were obtained via programmatic queries of the US Oncology Network/McKesson Specialty Health electronic health record database, supplemented with chart abstraction. Overall survival (OS) and time to treatment failure (TTF) were estimated from crizotinib initiation using the Kaplan–Meier (KM) method. Results: Of the n = 199 ALK-positive crizotinib-treated patients meeting eligibility criteria, crizotinib was prescribed as first line (1 L) in n = 123 (61.8%). The majority (88.9%) had confirmed adenocarcinoma histology and 32.2% had brain metastases at initial diagnosis. Median age at crizotinib initiation was 60.2 years (range 27.1–88.2); 54.8% were never smokers, 33.7% were former smokers. Treatment of 250 mg, twice daily, was most commonly prescribed (89.5%) with the dose unchanged from an initial dose in 79.4% of patients. The primary discontinuation reason was progression (n = 91, 58.7%). Patients (3.2%) were identified as discontinuing crizotinib as a result of treatment-related toxicity. With median follow-up time of 13.0 months (min–max = 0.03–46.6), median OS from crizotinib initiation was 33.8 months (95% CI = 24.3–38.8). Median TTF was 10.4 months. Conclusions: Crizotinib usage evaluated within the real-world setting is consistent with prior phase III clinical trial data, and illustrates the real-world effectiveness of crizotinib. Full article

Dialysis associated steal syndrome (DASS) is a relatively rare but debilitating complication of arteriovenous fistulas. While mild symptoms can be observed, if severe symptoms are left untreated, DASS can result in ulcerations and limb threatening ischemia. High-flow with resultant heart failure is another documented complication following dialysis access procedures. Historically, open surgical procedures have been the mainstay of therapy for both DASS as well as high-flow. These procedures included ligation, open surgical banding, distal revascularization-interval ligation, revascularization using distal inflow, and proximal invasion of arterial inflow. While effective, open surgical procedures and general anesthesia are preferably avoided in this high-risk population. Minimally invasive limited ligation endoluminal-assisted revision (MILLER) offers both a precise as well as a minimally invasive approach to treating both dialysis associated steal syndrome as well as high-flow with resultant heart failure. MILLER is not ideal for all DASS patients, particularly those with low-flow fistulas. We aim to briefly describe the open surgical therapies as well as review both the technical aspects of the MILLER procedure and the available literature. Full article

Introduction: Alcohol Use Disorders (AUD) are the most prevalent psychiatric diagnosis in the general population. The study of personality characteristics, using Cloninger Personality Inventory (TCI-R), allows us to know the evolution of these patients at the beginning of treatment. Material and Method: We conducted a cross-sectional, observational and descriptive study for 3 years with a total of 304 patients. We studied the severity of their alcohol disorder by the Alcohol Dependency Intensity Scale (EIDA), Scale of Obsessive Consumption Compulsive (OCDS) and European version of the Addiction Severity Index (EUROPASI); we studied the relationship with the personality traits of TCI-R. Results and conclusions: The personality lines influence the evolution of alcohol use disorder (AUD). People with higher scores on Reward Dependency (RD), Persistence (P), Cooperation (CO) and Autotranscendence (ST) have a better prognosis while people with higher scores on Search for Novelty (SN) and Avoidance of Damage (AD) have a worst prognosis. Women present differences in consumption in relation to men, as a consequence of their personality. Women have lower scores in Persistence (P) y Self-Transcendence (ST) which are associated with the greater severity of their addiction. Full article