Strength of selection pressure is an important parameter contributing to the complexity of antibiotic resistance evolution

Revealing the genetic changes responsible for antibiotic resistance can be critical for developing novel antibiotic therapies. However, systematic studies correlating genotype to phenotype in the context of antibiotic resistance have been missing. In order to fill in this gap, we evolved 88 isogenic Escherichia coli populations against 22 antibiotics for 3 weeks. For every drug, two populations were evolved under strong selection and two populations were evolved under mild selection. By quantifying evolved populations' resistances against all 22 drugs, we constructed two separate cross-resistance networks for strongly and mildly selected populations. Subsequently, we sequenced representative colonies isolated from evolved populations for revealing the genetic basis for novel phenotypes. Bacterial populations that evolved resistance against antibiotics under strong selection acquired high levels of cross-resistance against several antibiotics, whereas other bacterial populations evolved under milder selection acquired relatively weaker cross-resistance. In addition, we found that strongly selected strains against aminoglycosides became more susceptible to five other drug classes compared with their wild-type ancestor as a result of a point mutation on TrkH, an ion transporter protein. Our findings suggest that selection strength is an important parameter contributing to the complexity of antibiotic resistance problem and use of high doses of antibiotics to clear infections has the potential to promote increase of cross-resistance in clinics

Central Sagittal Angle of the Sacrum as a New Risk Factor for Patients with Persistent Low Back Pain after Caesarean Section

Study DesignRetrospective.PurposeThis study investigated the possible association of persistent low back pain (LBP) with caesarean section (CS) under spinal anesthesia.Overview of LiteratureMany women suffer from LBP after CS, which is commonly performed under spinal anesthesia. However, this type of LBP is poorly understood, and there is poor consensus regarding increased risk after spinal anesthesia.MethodsWe examined two groups of patients who underwent cesarean delivery under spinal anesthesia. Group I included patients who presented to a neurosurgical clinic complaining of LBP for at least 6 months. Group II was a control group with patients without LBP. We analyzed clinical and sagittal angle parameters, including age, body mass index, parity, central sagittal angle of the sacrum (CSAS), and sacral slope (SS).ResultsFifty-three patients participated in this study: 23 (43.1%) in Group I and 30 (56.9%) in Group II. Non-parametric Mann–Whitney U-tests showed that age, parity, and CSAS significantly differed between the two groups at 6 months.ConclusionsAge, parity, and CSAS appear to be associated with increased risk for LBP after CS under spinal anesthesia. Future prospective studies on this subject may help validate our results

Sex difference and intra-operative tidal volume: Insights from the LAS VEGAS study

BACKGROUND: One key element of lung-protective ventilation is the use of a low tidal volume (VT). A sex difference in use of low tidal volume ventilation (LTVV) has been described in critically ill ICU patients.OBJECTIVES: The aim of this study was to determine whether a sex difference in use of LTVV also exists in operating room patients, and if present what factors drive this difference.DESIGN, PATIENTS AND SETTING: This is a posthoc analysis of LAS VEGAS, a 1-week worldwide observational study in adults requiring intra-operative ventilation during general anaesthesia for surgery in 146 hospitals in 29 countries.MAIN OUTCOME MEASURES: Women and men were compared with respect to use of LTVV, defined as VT of 8 ml kg-1 or less predicted bodyweight (PBW). A VT was deemed 'default' if the set VT was a round number. A mediation analysis assessed which factors may explain the sex difference in use of LTVV during intra-operative ventilation.RESULTS: This analysis includes 9864 patients, of whom 5425 (55%) were women. A default VT was often set, both in women and men; mode VT was 500 ml. Median [IQR] VT was higher in women than in men (8.6 [7.7 to 9.6] vs. 7.6 [6.8 to 8.4] ml kg-1 PBW, P < 0.001). Compared with men, women were twice as likely not to receive LTVV [68.8 vs. 36.0%; relative risk ratio 2.1 (95% CI 1.9 to 2.1), P < 0.001]. In the mediation analysis, patients' height and actual body weight (ABW) explained 81 and 18% of the sex difference in use of LTVV, respectively; it was not explained by the use of a default VT.CONCLUSION: In this worldwide cohort of patients receiving intra-operative ventilation during general anaesthesia for surgery, women received a higher VT than men during intra-operative ventilation. The risk for a female not to receive LTVV during surgery was double that of males. Height and ABW were the two mediators of the sex difference in use of LTVV.TRIAL REGISTRATION: The study was registered at Clinicaltrials.gov, NCT01601223

Being Outside and Apart: Impoverished Youths' Relations with Locales

The relationships of women and youths, who have both been described in studies on poverty in Turkey as the most disadvantaged groups, to the city and venues has not been adequately addressed. Exclusion from venues, a manifestation of social exclusion, has been said to create many problems in the daily lives of impoverished youths. In this context, the process of spatial exclusion plays an important role in shaping youths' daily lives and their life choices. Impoverished youths' establishment of a relationship with locales needs to be the subject of both poverty and youth researches as a variable. In this study, the process of spatial exclusion for impoverished youths and the problems that this brings has been discussed on the basis of this necessity. In this context, spatial exclusion practices on impoverished youths were evaluated from the data of poverty and youth-related field studies conducted in Turkey. The field research data used in this study was mostly based on qualitative research. This study has concluded that in order to ensure spatial inclusion for impoverished youths who have been excluded from venues and remain apart is the basic approach of the capacity to experience. Experiencing requires being at a venue together with the people who have created it; experiencing requires contact. This experience makes it possible for one to call one's self into being both socially and spatially

Enzyme Inhibitors and Activators

Over the recent years, medicinal chemistry has become responsible for explaining interactions of chemical molecule processes such that many scientists in the life sciences from agronomy to medicine are engaged in medicinal research. This book contains an overview focusing on the research area of enzyme inhibitor and activator, enzyme-catalyzed biotransformation, usage of microbial enzymes, enzymes associated with programmed cell death, natural products as potential enzyme inhibitors, protease inhibitors from plants in insect pest management, peptidases, and renin-angiotensin system. The book provides an overview on basic issues and some of the recent developments in medicinal science and technology. Especially, emphasis is devoted to both experimental and theoretical aspect of modern medicine. The primary target audience for the book includes students, researchers, chemists, molecular biologists, medical doctors, pharmacologists, and professionals who are interested in associated areas. The textbook is written by international scientists with expertise in biochemistry, enzymology, molecular biology, and genetics, many of which are active in biochemical and pharmacological research. I would like to acknowledge the authors for their contribution to the book. We hope that the textbook will enhance the knowledge of scientists in the complexities of some medical approaches; it will stimulate both professionals and students to dedicate part of their future research in understanding relevant mechanisms and applications of pharmacology

Assessment scale of academic enablers: A validity and reliability study Akademik Yetkinlik Araçları Değerlendirme Ölçeği: Geçerlik ve Güvenirlik Çalışması

Purpose: This study aims to determine how university students evaluate the academic enablers they have acquired. To this end, the Assessment Scale of the Academic Enablers (ASAE) was developed and applied to 5,208 university students to test its validity and reliability

Comparison of blood carbonic anhydrase activity of athletes performing interval and continuous running exercise at high altitude

The effects of high-intensity interval and continuous exercise on erythrocytes carbonic anhydrase (CA, EC 4.2.1.1) activity levels were scarcely investigated up until now. Here we present a study focused on the CA activity from erythrocytes of athletes experiencing interval and continuous training for 6 weeks, during cold weather and at high altitude (> 1600 m). We observed a 50% increase in the blood CA activity at the second week after initiation of the training in both interval and continuos running groups, whereas the control group did not experience any variation in the enzyme activity levels. In the trained individuals a mild decrease in their body mass, BMI and an increased were also observed. The CA activity returned at the basal values after 4–6 weeks after the training started, probably proving that a metabolic compensation occurred without the need of an enhanced enzyme activity. The unexpected 50% rise of activity for an enzyme which acts as a very efficient catalyst for CO2 hydration/bicarbonate dehydration, such as the blood CA, deserves further investigations for better understanding the physiologic basis of this phenomenon