Osteoporosis, bisphosphonate use, and risk of moderate or worse hearing loss in women.
Osteoporosis and low bone density (LBD) may be associated with higher risk of hearing loss, but findings are inconsistent and longitudinal data are scarce. Bisphosphonates may influence risk, but the relation has not been studied in humans. We longitudinally investigated associations of osteoporosis and LBD, bisphosphonate use, vertebral fracture (VF), hip fracture (HF), and risk of self-reported moderate or worse hearing loss. Longitudinal cohort study. The Nurses' Health Study (NHS) (1982-2016) and Nurses' Health Study II (NHS II) (1995-2017). Participants included 60,821 NHS women, aged 36-61 years at baseline, and 83,078 NHS II women, aged 31-48 years at baseline (total n = 143,899). Information on osteoporosis, LBD, bisphosphonate use, VF, HF, and hearing status was obtained from validated biennial questionnaires. In a subcohort (n = 3749), objective hearing thresholds were obtained by audiometry. Multivariable-adjusted Cox proportional hazards models were used to examine independent associations between osteoporosis (NHS), osteoporosis/LBD (NHS II), and risk of hearing loss. The multivariable-adjusted relative risk (MVRR, 95% confidence interval) of moderate or worse hearing loss was higher among women with osteoporosis or LBD in both cohorts. In NHS, compared with women without osteoporosis, the MVRR was 1.14 (1.09, 1.19) among women with osteoporosis; in NHS II, the MVRR was 1.30 (1.21, 1.40) among women with osteoporosis/LBD. The magnitude of the elevated risk was similar among women who did and did not use bisphosphonates. VF was associated with higher risk (NHS: 1.31 [1.16, 1.49]; NHS II: 1.39 [1.13, 1.71]), but HF was not (NHS: 1.00 [0.86, 1.16];NHS II: 1.15 [0.75,1.74]). Among participants with audiometric measurements, compared with women without osteoporosis/LBD, the mean multivariable-adjusted hearing thresholds were higher (i.e., worse) among those with osteoporosis/LBD who used bisphosphonates. Osteoporosis and LBD may be important contributors to aging-related hearing loss. Among women with osteoporosis, the risk of hearing loss was not influenced by bisphosphonate use.


Pep34, a synthetic peptide whose sequence corresponds to the intracytoplasmic domain of the Epstein-Barr virus receptor (CR2, CD21), regulates human B lymphocyte proliferation triggered through CR2.
CR2 is involved in regulation of human B lymphocyte proliferation by interacting, through distinct domains, with extracellular, cell surface or intracellular components. Contribution of CR2 intracytoplasmic domain in CR2 regulatory functions remains unclear. Thus, we used pep34, a 34 amino acid synthetic peptide whose sequence corresponds to CR2 intracytoplasmic domain. Pep34 was incorporated into B lymphocytes which were then activated by EBV or C3d through CR2. Our data demonstrate that pep34 inhibits 100% B lymphocyte proliferation triggered by EBV or C3d. Irrelevant peptide had no effect. When B lymphocyte proliferation was triggered by a multipotent B cell activator as SAC, pep34 did not exert any inhibitory effect. Our data demonstrate that pep34 inhibits B lymphocyte proliferation only when lymphocytes are triggered through CR2. Thus, this strongly supports that despite its short length. CR2 intracytoplasmic domain participates to regulatory functions of this receptor.


Tissue responses to thyroid hormone in a kindred with resistance to thyroid hormone harboring a commonly occurring mutation in the thyroid hormone receptor beta gene (P453T).
Resistance to thyroid hormone (RTH) is a dominantly inherited syndrome of reduced tissue responsiveness to thyroid hormone (TH) usually due to mutations in the TH receptor beta gene (TRbeta). We studied pituitary and peripheral tissue responses to graded doses of liothyronine (L-T3) in 5 affected members (2 children and 3 adults) of a family with RTH due to the common TRbeta mutation P453T. Overall, the 5 subjects studied exhibited suppressed thyrotropin response to thyrotropin-releasing hormone of 51% +/- 8%, 12.1% +/- 1.5%, and 6.3% +/- 3% of the 100% baseline on 50, 100, and 200 microg/dL L-T3, respectively. This degree of suppression was greater than that observed in subjects with RTH due to other TRbeta mutations, indicating less resistance. Compared with normal subjects, however, the family described here demonstrated less suppression by L-T3, compatible with their RTH, although of a mild magnitude. The 2 children with RTH demonstrated less L-T3-mediated suppression of prolactin and cholesterol than the adults. Patients often receive thyroid ablative therapy before the diagnosis of RTH and are left with variable degrees of hypothyroidism. Our results demonstrate that graded doses of L-T3 can be used to evaluate RTH patients, even under the condition of limited thyroid reserve, when results are compared with their baseline. We demonstrate that RTH patients can be evaluated either on or off thyroid hormone and still be distinguished from hypothyroid subjects without RTH.


Development of Beau's lines in two patients receiving azathioprine.
We report two cases of patients who developed Beau's lines while taking azathioprine. In each case, the patient developed a hypersensitivity reaction to the medication. These are the first reported cases of a hypersensitivity reaction to azathioprine leading to Beau's lines.


Racial disparities in the development of comorbid conditions after preterm birth: A narrative review.
Despite recognition and attempts to reduce racial disparities in perinatal outcomes, Black infants are still disproportionately represented among those who are born preterm. Postnatal investigations of racial disparities in comorbidities and outcomes after preterm birth are increasing, although their results and interpretations are conflicting. In the present review, we 1.) identify important methodological limitations of that literature 2.) summarize the conflicting literature investigating racial disparities, specifically Black-white differences, in postnatal comorbidities and outcomes after preterm birth 3.) describe mechanisms by which racism operates to contextualize our understanding to inform future work to actively reduce disparities in preterm birth and subsequently, its complications.


Skin damage prevention in the prone ventilated critically ill patient: A comprehensive review and gap analysis (PRONEtect study).
Ventilating critically ill patients with acute respiratory distress syndrome in the prone position is a life-saving strategy, but it is associated with adverse consequences such as skin damage. To identify, review and evaluate international proning and skin care guidelines and make an inventory of commonly used equipment and training resources. A gap analysis methodology was applied. 1) Comprehensive search and evaluation of proning and skin care guidelines, 2) extensive search and listing equipment and educational resources, and 3) international consultation with 11 experts (8 countries). A variety of sources researched through July 2021 were used to identify relevant literature: (1) scientific literature databases and clinical trials registries, (2) intensive care and wound care associations, (3) healthcare organisations, (4) guideline development organisations, and (5) the Google search engine. Eleven international experts reviewed the literature and provided insights in two, 2-h online sessions. The search yielded 24 guidelines. One clinical practice guideline had high methodological quality. Twenty-five devices/equipment and sixteen teaching materials were identified and discussed with the expert panel. The gap analysis identified a lack of concise, accessible, evidence-based guidelines and educational materials of short duration. This analysis forms the basis for designing a competency-based education and training intervention for an interdisciplinary team caring for the skin of critically ill patients in the prone position. The results can assist the multidisciplinary team to review their current protocol for prone positioning. This is a first step in developing a training package for clinicians.


Video Analysis of 26 Cases of Second ACL Injury Events in Collegiate and Professional Athletes.
Significant effort has gone into the identification and quantification of the underlying mechanisms of primary ACL injury. Secondary ACL injury is observed in approximately 1/4 to 1/3 of athletes who return to sport following ACL reconstruction. However, little has been done to evaluate the mechanisms and playing circumstances surrounding these repeat injuries. The purpose of this study was to characterize the mechanisms of non-contact secondary ACL injuries using video analysis. It was hypothesized that in video recordings of secondary ACL injury, athletes would exhibit greater frontal plane hip and knee angles, but not greater hip and knee flexion, at 66 ms following initial contact (IC) as compared to at IC and 33ms following IC. Cross-Sectional Study. Twenty-six video recordings of competitive athletes experiencing secondary ACL ruptures via noncontact mechanisms were analyzed for lower extremity joint kinematics, playing situation, and player attention. Kinematics were assessed at IC as well as 33 ms (1 broadcast frame) and 66 ms (2 broadcast frames) following IC. Knee flexion and knee frontal plane angles were greater at 66 ms than IC (p ≤ 0.03). Hip, trunk, and ankle frontal plane angles were not greater at 66 ms than IC (p ≥ 0.22). Injuries were distributed between attacking play (n=14) and defending (n=8). Player attention was most commonly focused on the ball (n=12) or an opponent (n=7). A single-leg landing accounted for just over half of the injuries (54%), while a cutting motion accounted for the remainder of the injuries (46%). Secondary ACL injury was most likely to occur during landing or a sidestep cut with player attention external to their own body. Knee valgus collapse combined with limited hip motion was identified in the majority of secondary injuries. Level IIIb.


Cytokines and the chronic inflammation of rheumatic disease. II. The presence of interleukin-2 in synovial fluids.
Sera and synovial fluids from patients with a variety of rheumatic diseases were assayed for interleukin-2 (IL-2) activity in a system utilizing the proliferative response of cultured human phytohaemagglutinin (PHA) T cell blasts. The synovial fluids from 14 rheumatoid arthritis, eight ankylosing spondylitis, three psoriatic arthritis and 11 osteoarthritis patients, all showed IL-2 activity. The amounts of IL-2 present in the fluids from different diseases were compared and ranged from 4.2 to 140.0 units/ml.


Protective effects of fructose-1,6-diphosphate on acute and chronic doxorubicin cardiotoxicity in rats.
The effects of fructose-1,6-diphosphate, an intermediate metabolite of glycolysis, on acute and chronic cardiotoxicity of doxorubicin were investigated in rats. In the acute study, urethane-anaesthetized Wistar female rats treated with 10 mg/kg i.v. doxorubicin developed a widening of the S alpha T segment, an impairment of +dP/dtmax, and tachycardia. Pretreatment with 375 and 750 mg/kg i.p. fructose-1,6-diphosphate prevented the S alpha T segment from widening, whereas only 750 mg/kg i.p. significantly attenuated the heart rate increase. Chronic cardiomyopathy was induced over a 6-week period by weekly doses of 3 mg/kg i.v. doxorubicin, being characterized in vivo by the progressive enlargement of the S alpha T segment and the occurrence of histological alterations and in vitro by a marked impairment of the inotropic response elicited by adrenaline in isolated hearts from treated rats. Concurrent treatment with 150 and 300 mg/kg i.p. fructose-1,6-diphosphate thrice a week for 6 weeks did not lessen the chronic heart damage, whereas 600 mg/kg given i.p. significantly reduced the widening of the S alpha T segment and the severity of histological damage in vivo, as well as significantly improving the contractile responses of hearts in vitro. These findings suggest that the administration of fructose-1,6-diphosphate plays a protective role in the acute and chronic cardiotoxicity of doxorubicin in the rat.


[Simultaneous determination of water-soluble components and nerolidol in xiangdan injection by high performance liquid chromatography with column switching].
Integrating column switching for on-line concentration and programmed injection, a novel HPLC method is developed for simultaneous determination of high-content water-soluble components (danshensu, protocatechualdehyde, salvianolic acid B) and trace nerolidol in Xiangdan injection. The concentrations of water-soluble components in Xiangdan injection are roughly 1000 times of that of nerolidol. The on-line concentration was performed on a Zorbax SB-C18 guard column. The separation was carried out on Lichrospher C18 column (4.6 mm x 250 mm, 5 microm). The mobile phase of guard column was mixtures of acetonitrile and 1.0% acetic acid water, and the flow rate was 0.5 mL x min(-1). The mobile phase of the analytical column was mixtures of acetonitrile and 0.05% acetic acid water, and the flow rate was set at 1.0 mL x min(-1). The column temperature was maintained at 40 degrees C, and the detection wavelength was 280 nm at 0-40 min, 210 nm at 40-55 min. The program injection was 10 microL of sample solution 1 at 0 min, 200 microL of sample solution 2 at 15.3 min. The calibration curves of danshensu, protocatechualdehyde, salvianolic acid B and nerolidol showed good linear regression (R2 > 0.9990) within investigated concentration ranges. The average recoveries of the four analytes were between l00% and 102%, and the RSD values were less than 3.0%. For danshensu, protocatechualdehyde, salvianolic acid B and nerolidol, the limits of detection at a signal-to-noise (S/N) ratio of 3 were 17.1, 0.473, 60.2, 50.6 microg x L(-1), respectively. The method is a simple, sensitive and repeatable approach. More importantly, results indicate that the present method shows promising prospect for quality control of Xiangdan injection.


A comparison of gingival marginal gap formation in composite inlays using three different fabrication techniques.
The purpose of this study was to evaluate the accuracy of composite inlays fabricated with three different techniques. Using 2-factor ANOVA it was found that after light curing, the Direct Method was the most accurate. After readapting and heat curing, the Indirect Method was not different from the Direct Method. The same was true after 24 hours' storage in water. The direct method is recommended if proximal contours and contact can be adequately controlled. If an Indirect Method is used, it is recommended that the laboratory use an additional cured layer of composite material in the gingival margin after initial curing to minimize the gaps.


Comparisons between main and ratoon crops in resource use efficiencies, environmental impacts, and economic profits of rice ratooning system in central China.
Rice production in China is constrained by excessive water consumption, labor shortage, large environmental footprint, and low economic profit. Rice ratooning is a promising practice to increase famers' profit with higher resource use efficiency and less environmental impact compared with other rice cropping systems. However, there is limited information on the differences in energy use efficiency, water and labor productivity, environmental footprint, and economic return between main crop (MC) and ratoon crop (RC) in this cropping system. This study was conducted to compare the system performance between the two crops of ratoon rice using on-farm survey data. Average grain yield was 8.40 and 4.55 t ha-1 for MC and RC, respectively. Although RC produced 45.9% lower grain yield, it had 57.3% less total energy input and 71.0% lower total production cost than MC, which resulted in a significantly higher energy use efficiency, net energy ratio, net economic return and benefit-to-cost ratio. Lower total energy input and production cost of RC was mainly attributed to the reduction in fertilizer application and labor input, respectively compared with MC. In addition, both labor and water productivity of RC was significantly higher than those of MC. Furthermore, the global warming potential (GWP) and yield-scaled GWP of RC was 59.3% and 23.4% lower than those of MC, respectively, due to lower agronomic inputs and GHGs emissions. Overall, our results suggested that RC had higher resource use efficiency, better economic performance, and less environment impact compared with MC.


Uteroplacental resistance index: analysis of intra- and interobserver variability.
The aim of this study was to assess the intra- and interobserver variability of second-trimester uteroplacental continuous-wave flow velocity waveforms. The left and right uterine and arcuate resistance indices were measured in women having their routine booking scan at 16-24 weeks' gestation. Four experiments assessed the intra-observer between-frame variability, the intraobserver beat-to-beat variability, the intraobserver temporal variability, and the interobserver variability, using the limits-of-agreement method. The intraobserver between-frame variability was greater than the beat-to-beat variability at three of the four sites. The temporal variability was not significantly different between sites. There were wide interobserver limits of agreement with respect to the reference ranges, although they were greater at arcuate sites than uterine sites. These observations suggest that the reproducibility of the resistance index in continuous wave Doppler uteroplacental flow velocity waveforms is poor, particularly from arcuate sites. The uterine site is preferable and descriptive analysis may be better.


Home birth with certified nurse-midwife attendants in the United States. An overview.
The move of the birth site from home to hospital in the United States from 1800 through the early part of the 20th Century is described. The reemergence of home birth in the United States since the early 1960s and the evolution of nurse-midwifery care in the home birth setting are discussed. Misconceptions regarding home birth and a review of international literature documenting the safety of home birth are included. The need for prospective research on home birth is supported. A Home Birth Curriculum Guide developed by the Home Birth Committee of the American College of Nurse-Midwives is provided.


Association of whole blood copper, magnesium and zinc levels with metabolic syndrome components in 6-12-year-old rural Chinese children: 2010-2012 China National Nutrition and Health Survey.
Metabolic syndrome (MetS) is significantly associated with the risk of cardiovascular disease and its prevalence is showing a trend of getting younger. Previous studies on the relationship between elements and MetS were mostly reported in adults with single element analysis, while reports in children with combined effects of multiple elements were very limited. The aim of this study is to investigate the association between whole blood Cu, Mg and Zn in both single and combined effects and MetS components in rural Chinese children aged 6-12 years based on the data from 2010-2012 China National Nutrition and Health Survey. A total of 911 children (51.2% male, 48.7% female) aged 6-12 years were included. Basic characteristics and MetS component parameters were collected and determined by trained stuffs. Elements were detected by Inductively Coupled Plasma Mass Spectrometry (ICP-MS). Multivariate logistic regression analysis was performed to examine the independent relationship between elements and MetS components. In single metal analysis, copper was positively associated with elevated waist (OR = 2.00, 1.18-3.28) and all of the metals were associated with elevated TG. And the comprehensive analysis of multiple elements were mostly consistent with the results of single element analysis (low Cu + high Zn with elevated TG (OR = 2.21, 1.18-4.13), high Cu + low Mg with elevated TG (OR = 0.40, 0.16-0.95), high Cu + high Mg with elevated waist (OR = 2.03, 1.26-3.27)), except the combination of Zn and Mg (high Zn + low Mg with reduced HDL-C (OR = 0.47, 0.28-0.77)). Our study suggested Cu, Zn and Mg in children are indeed associated with metabolic syndrome components, whether in single element or multi-element combined analysis. The results will be confirmed through additional cohort research.


Validation of the Muscle Tightness Measurement Tool.
For nurses, muscle tightness is an important aspect of patient care, but no bedside tool is available that allows them to measure it. Therefore, a standardized tool that measures muscle tightness is needed. The purpose of this study was to validate a tool to measure muscle tightness. Using Delphi technique and quantitative design, the tool was validated in two phases. The phase 1 included 20 expert clinicians who established content validity with Lawshe's rating. In phase 2, divergent validity was established by administering the tool to one group that had muscle tightness (n = 26) and one group that did not (n = 20). Findings indicate that the muscle tightness measurement tool has content and divergent validity. Further tool refinement with validity and reliability studies are recommended for clinical practice.


Mutations in the hrp48 gene, which encodes a Drosophila heterogeneous nuclear ribonucleoprotein particle protein, cause lethality and developmental defects and affect P-element third-intron splicing in vivo.
The Drosophila melanogaster hnRNP protein, hrp48, is an abundant heterogeneous nuclear RNA-associated protein. Previous biochemical studies have implicated hrp48 as a component of a ribonucleoprotein complex involved in the regulation of the tissue-specific alternative splicing of the P-element third intron (IVS3). We have taken a genetic approach to analyzing the role of hrp48. Mutations in the hrp48 gene were identified and characterized. hrp48 is an essential gene. Hypomorphic mutations which reduce the level of hrp48 protein display developmental defects, including reduced numbers of ommatidia in the eye and morphological bristle abnormalities. Using a P-element third-intron reporter transgene, we found that reduced levels of hrp48 partially relieve IVS3 splicing inhibition in somatic cells. This is the first direct evidence that hrp48 plays a functional role in IVS3 splicing inhibition.


Methods for ASL measurements and mucus transport rates in cell cultures.
The healthy human respiratory tract is lined with a pseudostratified epithelia composed of ∼80% ciliated cells and ∼20% goblet cells. These cells produce and are bathed by a layer of airway surface liquid (ASL), which plays a critical role in lung defense by helping to maintain the sterility of the lung. This layer is composed of two phases: the mucus layer which functions to trap particulates, bacteria, and viruses, and the underlying periciliary liquid layer (PCL), which provides hydration, enabling mucus transport and clearance. This chapter describes the methods used to measure the structure and height of the ASL by XZ confocal microscopy and mucus transport rates using epifluorescent microscopy in live airway cultures. Furthermore, we also demonstrate that these methods are also applicable in novel ways to probe the ultrastructure of the airways including the establishment of pH gradients and the ability of the apical membrane glycocalyx in excluding larger molecules from the cell surface.


Comparative study of different osteotomy modalities in maxillary distraction osteogenesis for cleft lip and palate.
Conventional maxillary distraction osteogenesis and anterior maxillary segmental distraction were applied in the treatment of severe maxillary hypoplasia secondary to cleft clip and palate. The aim of the present study was to compare the difference between these 2 osteotomy modalities used for rigid external distraction. Ten patients with severe maxillary hypoplasia secondary to CLP were enrolled in our study. They were randomly divided into 2 groups. Conventional maxillary distraction osteogenesis was performed in 5 patients and anterior maxillary segmental distraction in 5 patients. The preoperative and postoperative lateral cephalograms were compared, and cephalometric analysis was performed. The independent sample t test was used to evaluate the differences between the 2 groups. All patients healed uneventfully, and the maxillae moved forward satisfactorily. The sella-nasion-point A angles, nasion-point A-Frankfort horizontal plane angles, overjets, and 0-meridian to subnasale distances had increased significantly after distraction osteogenesis. Significant differences were found in the changes in palatal length between the 2 groups (P < .05). A mean increase of 7.50 mm in palatal length was found in the anterior maxillary segmental distraction group. No significant difference in the changes in palatopharyngeal depth or soft palatal length was found. With the ability of increasing the palatal and arch length, avoiding changes in palatopharyngeal depth, and preserving palatopharyngeal closure function, anterior maxillary segmental distraction has great value in the treatment of maxillary hypoplasia secondary to CLP. It is a promising and valuable technique in this potentially complicated procedure.


The association between personality traits and treatment outcomes in Korean patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH): a preliminary study.
We investigated the association between personality traits and treatment outcomes in male Korean patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH). We evaluated the personality traits and the severity of LUTS/BPH symptoms at baseline using the Korean versions of the 44-item Big Five Inventory (BFI-K) and International Prostate Symptom Score (IPSS), respectively. The IPSS was re-administered following a 12-week routine treatment regime, and we examined the relationship between treatment outcome and personality traits. Of the 176 patients initially screened, 101 agreed to participate in the study. Of those, 93 (92.1%) completed the 12-week trial and the BFI-K. Neuroticism was associated with a significantly worse treatment response, whereas extraversion was associated with a significantly better treatment response, and openness was associated with a high responder rate. Agreeableness, openness and conscientiousness were associated with improved week-12 IPSS total scores; however, the results were not statistically significant. We found an association between treatment response and personality traits of neuroticism, extraversion and openness in patients with LUTS/BPH. However, further studies with larger samples and an improved design are needed to support our findings.


Reflecting on research: sharpening nurses' focus through engaged learning.
The Bedside Scientist Institute is a basic research course provided for nurses using an engaged, interactive learning environment. This qualitative study evaluated the course outcomes. A large Magnet®-designated teaching hospital provided the setting for both the education and the study. Coding categories and themes were identified from 16 interviews; a focus group confirmed the study findings. Culture change was facilitated by enlarging the perceptual field, reflecting on research evidence and the practice-research interface, and focusing on a new vision for evidence-based practice. Half of the nurses who participated returned to formal education. Participating in the Bedside Scientist Institute was transformative. The course opened participants' minds to question traditional practice, developing champions for research.


Chlorate--a potent inhibitor of protein sulfation in intact cells.
Chlorate is known to be an in vitro inhibitor of ATP-sulfurylase, the first enzyme in the biosynthesis of PAPS which is the ubiquitous co-substrate for sulfation. Here, the effect of chlorate on protein sulfation in intact cells was investigated. Treatment of various cell cultures with 1 mM sodium chlorate in a medium low in sulfate and sulfur-containing amino acids resulted in an inhibition of protein sulfation greater than 95%. Tyrosine as well as carbohydrate sulfation was blocked. Chlorate did not inhibit protein synthesis and did not exhibit any other toxic effects, even after prolonged treatment of cell cultures. Thus, chlorate treatment provides a powerful tool for studying the biological significance of protein sulfation.


Trends in Robot-Assisted Procedures for General Surgery in the Veterans Health Administration.
Implementation of robot-assisted procedures is growing. Utilization within the country's largest healthcare network, the Veterans Health Administration, is unclear. A retrospective cohort study using data from the Department of Veterans Affairs Corporate Data Warehouse from January 2015 through December 2019. Trends in robot utilization for cholecystectomy, ventral hernia repair, and inguinal hernia repair were characterized nationally and regionally by Veterans Integrated Services Network. Patients, who underwent laparoscopic repairs for these procedures and open hernia repairs, were included to determine proportion performed robotically. We identified 119,191 patients, of which 5689 (4.77%) received a robotic operation. The proportion of operations performed robotically increased from 1.49% to 10.55% (7.08-fold change; slope, 2.14% per year; 95% confidence interval [0.79%, 3.49%]). Ventral hernia repair had the largest growth in robotic procedures (1.51% to 13.94%; 9.23-fold change; slope, 2.86% per year; 95% confidence interval [1.04%, 4.68%]). Regions with the largest increase in robotic utilization were primarily along the Northeast, Midwest, and West Coast. Robot utilization in general surgery is increasing at different rates across the United States in the Veterans Health Administration. Future studies should investigate the regional disparities and drivers of this approach.


A simple ratiometric fluorescent probe for two-photon imaging of carbon monoxide in living cells and zebrafish.
Carbon monoxide (CO) is an important gas signaling molecule and has been widely involved in regulating important life processes. Effective monitoring of CO in living systems is critical. Combined with the accuracy of ratio detection and the advantages of two-photon imaging, a simple ratiometric two-photon fluorescent probe RTFP was rationally designed and synthesized using 7-(diethylamino)-4-hydroxycoumarin as a two-photon fluorophore and allyl carbonate as the reactive unit. Probe RTFP exhibited excellent selectivity and sensitivity towards CO, and was successfully applied to image endogenous CO in living cells and zebrafish.


One-stage operation for obstructing carcinomas of the left colon and rectum.
A consecutive series of 28 patients with acutely obstructing carcinomas of the left colon and rectum were encountered during the last three years. Two patients treated by loop colostomy only were excluded from the study. Fifteen patients received a one-stage operation of immediate resection and primary anastomosis without proximal colostomy. The remaining 11 patients were treated by a conventional staged operation. The operative mortality and complications were similar in both groups. The duration of hospital stay in the former was half of that in the latter. Of nine patients treated by subtotal or total colectomy with primary anastomosis, the average number of bowel movements three months after surgery was 1.8 per day. Intraoperative colonic irrigation was performed in five patients of the one-stage group and permitted a safe primary anastomosis. The immediate results of the one-stage operation were surprisingly good. The authors propose it as the treatment of choice for the majority of patients with obstructing carcinomas of the left colon and rectum.


Determining the orientation of acetabular prosthesis in total hip arthroplasty by refering to the anatomical landmarker of acetabular notches.
The aim of this study was to explore a novel method to determine the orientation of acetabular prosthesis in total hip arthroplasty (THA) by refering to the anatomical landmarker of acetabular notches. Forty-one normal developmental hips were included in the present study. The acetabulums were reamed according to standard surgical procedures of THA on life-size 3D printing pelvis models. The inferior edge of acetabular cup were placed (1-5) mm proximal and distal to the proximal line of the anterior and posterior acetabular notches (PLAPAN) respectively to determine cup inclination. The inferior edge of acetabular cup were placed (1-5) mm pronating and supinating around the proximal point of acetabular posterior notch (PPAPN) respectively to determine cup anteversion. The pelvis plain radiographs were took and the inclination and anteversion of the acetabular cup at 22 positions were calculated. In the normal developmental hip, the mean inclination of acetabular prothesis were (35.10 ± 3.22)° and (45.90 ± 2.68)° when the inferior edge of the acetabular cup was 3 mm proximal and 1 mm distal to the PLAPAN. The optimal cup inclination could be obtained when the inferior edge of the acetabular cup was 1 mm proximal to the PLAPAN (the mean inclination was (40.71 ± 2.80)°). The mean anteversion of acetabular prothesis were (10.67 ± 4.55)° and (20.86 ± 4.44)° when the inferior edge of the acetabular cup was 1 mm pronating and 1 mm supinating around the PPAPN. The optimal cup anteversion could be obtained when the inferior edge of the acetabular cup was parallel to the PLAPAN (the mean anteversion was (18.00 ± 1.64)°). The inclination and anteversion of acetabular prosthesis could be determined by refering the anatomical landmarks of acetabular notches, which could help orthopedists to install the acetabular prosthesis quickly and safely in THA.


High rates of sustained virological response in hepatitis C virus-infected injection drug users receiving directly observed therapy with peginterferon alpha-2a (40KD) (PEGASYS) and once-daily ribavirin.
This retrospective study evaluated the efficacy and tolerability of directly observed therapy with peginterferon alfa-2a and once-daily ribavirin (RBV) for chronic hepatitis C in 49 opioid-addicted injection drug users (IDUs) participating in a drug treatment program at a specialized outpatient center. Patients also received prophylactic citalopram to minimize the risk of interferon-induced depression. Patients had daily access to and support from specialist physicians, nurses and counseling services at the center, and a 24-hour helpline. Sustained virological response was achieved by 48 of 49 patients (98%) overall, including 20 of 21 (95%) hepatitis C virus (HCV) Genotype 1/4-infected patients and 28 of 28 (100%) Genotype 2/3-infected patients. Treatment was well tolerated, and no unexpected side effects of peginterferon treatment were seen. The safety profile of once-daily RBV was not different from twice-daily dosing. Decline in hemoglobin levels was similar to those reported in clinical trials including once-daily RBV and did not lead to dose reduction or treatment withdrawal. Our data demonstrate that HCV-infected IDUs on stable L-polamidone (methadone) or buprenorphine maintenance can be successfully and safely treated with peginterferon alfa-2a and RBV in an optimal substitution setting.


Iatrogenic spinal cord injury: an observational study.
Retrospective descriptive observational study. The primary objective of this study was to quantify the incidence of iatrogenic spinal cord injury (SCI) at our SCI unit (SCIU). The secondary objective was to discover the surgical and medical procedures that cause iatrogenic SCI and to estimate the incidence with each procedure. Patients admitted to or seen at outpatient services of the SCIU at a university hospital. Histories were compiled from 1 July 2005 to 30 June 2009. We included patients with SCI caused by any medical or surgical procedure. We collected age, sex, diagnosis leading to medical intervention, predominant clinical manifestations, medical-surgical procedure and level and grade of injury upon admission and discharge. Out of 250 patients admitted to the SCIU, 32 (14.7%) patients presented iatrogenic SCI. Average age was 56.2 (s.d. 17.3), ranging from 0 to 82 years old. The most frequent clinical manifestation was pain. The most common diagnosis was channel stenosis. Lumbar level grade C of American Spine Injury Association (ASIA) was the most frequently observed. The rise in the population's life expectancy entails an increase in elderly patients with vascular risk factors, who underwent invasive interventions leading to spinal cord iatrogenia.


Surface-constructing of visible-light Bi2WO6/CeO2 nanophotocatalyst grafted PVDF membrane for degradation of tetracycline and humic acid.
The synthesis of Bi2WO6 and CeO2 photocatalytic nanomaterials exhibit a great ability to photodegrade the antibiotics and shown excellent oxidation of various organic pollutants. Heterostructure 1:1 & 2:1 Bi2WO6/CeO2 nanocomposite was successfully synthesized via the facile sono-dispersion method and exquisite photocatalytic activity. The 0.5 wt% of nanocomposites were well-grafted on PVDF membrane surface via an in-situ polymerization method using polyacrylic acid. The fourier transform infrared (FTIR) spectra demonstrated that the network formation in PVDF induced by the -COOH functional group in acrylic acid. The grafted membrane morphology and strong binding ability over the membranes were validated by scanning electron microscope with energy dispersion (SEM-EDS) and X-ray photoelectron spectroscopy (XPS), respectively. The permeate flux of 49.2 L.m-2 h-1 and 41.65 L.m-2 h were observed for tetracycline and the humic acid solution respectively for 1 wt% of PVP and 0.5 wt% of photocatalytic nanomaterials in PVDF membrane. The tetracycline and humic acid photodegradation rate of 82% and 78% and total resistance of 1.43 × 1010 m-1 and 1.64 × 1010 m-1, 83.5% and 77% flux recovery ratio were observed with N5 membrane. The 2:1 Bi2WO6/CeO2 nanocomposite grafted membrane showed a high permeate flux and better photodegradation ability of organic pollutants in the wastewater.


3-{[6-(4-Chloro-phen-yl)imidazo[2,1-b][1,3,4]thia-diazol-2-yl]meth-yl}-1,2-benzoxazole.
In the title compound, C(18)H(11)ClN(4)OS, the benzisoxazole and imidazothia-diazole rings are inclined at an angle of 23.81 (7)° with respect to each other. The imidazothia-diazole and chloro-phenyl rings make a dihedral angle of 27.34 (3)°. In the crystal, inter-molecular C-H⋯N inter-actions generate a chain along the c axis and C-H⋯O inter-actions form centrosymmetric dimers resulting in an R(2) (2)(26) graph-set motif. Moreover, the C-H⋯N and S⋯N [3.206 (4) Å] inter-actions links the mol-ecules into R(7) ring motifs. The packing is further stabilized by π-π stacking inter-actions between the thia-diazole rings with a shortest centroid-centroid distance of 3.497 (3) Å. In addition, C-H⋯π inter-actions are observed in the crystal structure.


CFU-GM and T cell subsets in young red cell collections.
Young red cells (YRBCs) prepared using cell separators contain large numbers of white cells. The absolute numbers and percentages of different lymphocyte subsets and progenitor cells in YRBC collections were assessed before and after filtration through two white cell filters. It was found that the filters do not take up or selectively allow through any one lymphocyte subset and that the absolute number of T cells and progenitor cells in YRBC collections after filtration is less than that in normal donor blood.


Steroid-sparing effect of anakinra in giant-cell arteritis: a case series with clinical, biological and iconographic long-term assessments.
The treatment of GCA relies on corticosteroids but is burdened by a high rate of relapses and adverse effects. Anti-IL-6 treatments show a clear benefit with a significant steroid-sparing effect, but late relapses occur after treatment discontinuation. In addition to IL-6, IL-1 also appears to play a significant role in GCA pathophysiology. We report herein the efficacy of anakinra, an IL-1 receptor antagonist, in six GCA patients exhibiting corticosteroid dependence or resistance, specifically analysing the outcome of aortitis in four of them. This retrospective study analysed the cases of all GCA patients treated with anakinra from the French Study Group for Large Vessel Vasculitis. After a median duration of anakinra therapy of 19 (18-32) months, all six patients exhibited complete clinical and biological remission. Among the four patients with large-vessel involvement, one had a disappearance of aortitis under anakinra and three showed a decrease in vascular uptake. After a median follow-up of 56 (48-63) months, corticosteroids were discontinued in four patients, and corticosteroid dosage could be decreased to 5 mg/day in two patients. One patient relapsed 13 months after anakinra introduction in the context of increasing the daily anakinra injection interval to every 48 h. Three patients experienced transient injection-site reactions, and one patient had pneumonia. In this short series, anakinra appears to be an efficient and safe steroid-sparing agent in refractory GCA, with a possible beneficial effect on large-vessel involvement.


The impact of aerobic and anaerobic training regimes on blood pressure in normotensive and hypertensive rats: focus on redox changes.
This study was aimed to assess the impact of aerobic and anaerobic type of exercise on blood pressure and redox status in normotensive and hypertensive rats. After 1 week of preconditioning feeding and 1 week of preconditioning running regimen, Wistar albino rats (n = 72; bw: 270 ± 50 g) were randomly assigned to three groups according to running protocol (high-intensity interval training (HIIT) or moderate-intensity training (MIT)): sedentary control, MIT, HIIT; spontaneous hypertensive sedentary control (SHR), SHR + MIT and SHR + HIIT. Blood pressure (BP) measurement was performed by a tail-cuff noninvasive method BP system. After 48 h of rest following the final training, the rats were fasted for 24 h and sacrificed under ketamine/xylazine anesthesia and blood samples were collected. The level of the next prooxidants were measured: superoxide anion radical (O2-); hydrogen peroxide (H2O2); nitrite level (NO2-) and index of lipid peroxidation (thiobarbituric acid reactive substances), and the activity of antioxidative enzymes: reduced glutathione (GSH) superoxide dismutase (SOD) and catalase (CAT) activity. After the last week of running, HIIT strongly affected SP, DP, and HR in SHR rats compared to other hypertensive rats, as well as after MIT in normotensive conditions. We have found that HIIT training protocol induced a higher increase of O2- and H2O2 as compared to MIT. Findings of the present study pointed out that contrary to normotensive conditions, in hypertensive conditions both training regimes reduced the BP levels, which was more prominent in case of HIIT. In addition, MIT seems to be connected with milder disturbance of pro-oxidant production and better antioxidant response.


Periacetabular osteotomy for acetabular retroversion: A systematic review and meta-analysis.
The evidence for periacetabular osteotomy (PAO) when used in the management of acetabular retroversion remain limited. The review aims to answer the following questions: (1) What are the indications for an anteverting PAO for acetabular retroversion? (2) When are other concomitant procedures required when performing anteverting PAO for acetabular retroversion? (3) To what extent is an anteverting PAO able to correct acetabular retroversion? (4) What are the clinical outcomes for an anteverting PAO when used in acetabular retroversion? (5) What is the estimated survival for anteverting PAO when used in the treatment of acetabular retroversion, before other procedures need to be performed? (6) What are the complications and the complication rates when an anteverting PAO is performed? (7) How do the outcomes of an anteverting PAO compare to other surgical procedures used in the management of acetabular retroversion? The systematic review was conducted using the PRISMA guidelines. The search was conducted using PubMed Medical Literature Analysis and Retrieval System Online (MEDLINE) and Cumulative Index to Nursing and Allied Health Literature (CINAHL) from inception through 1 May 2020. The keywords used were "periacetabular osteotomy". All studies that reported the outcomes of periacetabular osteotomy for acetabular retroversion were included. Each study's data was then retrieved individually. The study design, surgical technique, indications, outcomes and complications of each study were analysed. Seven studies with 225 hips were included. The pooled odds ratio (OR) for a positive crossover sign and posterior wall sign preoperatively as compared to postoperatively were 456.31 (95% CI: 99.57 to 2091.28) and 53.45 (95% CI: 23.05 to 123.93) respectively. The pooled weighted mean difference (WMD) for studies with their mean preoperative LCEA and AI in the dysplastic range were 12.61 (95% CI: 6.54 to 18.68) and-15.0 (95% CI: -19.40 to -11.80) respectively, while the pooled WMD for studies with their mean preoperative LCEA and AI in the normal range were 3.43 (95% CI: 1.08 to 5.77) and -3.56 (95% CI: -5.29 to -1.83) respectively. Other indicators for acetabular retroversion correction, hip dysplasia correction, functional outcomes and range of motion were also significantly improved and sustained up till 11 years postoperatively. Only 7.1% of the hips required subsequent surgical procedures for impingement symptoms or progression of osteoarthritis, and the mean estimate for survival time across the studies was 123.90 months (95% CI: 119.94 to 127.86). The complication rates for low-grade complication were 31.6% while the rate for high-grade complications was 12.0%. Anteverting PAO is indicated for symptomatic acetabular retroversion, and when performed, leads to good deformity correction for both acetabular retroversion and hip dysplasia, positive improvement in clinical outcomes sustainable till 11 years postoperatively and a mean estimated survival time of more than 10 years. IV; Systematic review and meta-analysis.


Changes of expression of genes related to the activity of the gonadotrophin-releasing hormone pulse generator in young versus middle-aged male rats.
In females, it is well established that changes in the expression of neurotransmitters and peptides regulating the activity of the gonadotrophin-releasing hormone (GnRH) pulse generator are altered during ageing. By contrast, little is known about whether those age-related changes also occur in males. Therefore, we designed an animal study with orchidectomised young and middle-aged male rats to investigate changes in luteinising hormone (LH) secretion profiles and changes in the mRNA expression of genes regulating the activity of the GnRH pulse generator. Our results demonstrate that middle-aged rats exhibit lower serum LH levels and relatively fewer LH pulses with attenuated amplitude compared to young animals. Furthermore, upon ageing, GnRH mRNA expression is up-regulated in the preoptic area and the septum where GnRH neurones reside. Analysis of mRNA levels of glutamate decarboxylase (GAD) enzymes revealed that GAD(65) and GAD(67) mRNA expression increased in the mediobasal hypothalamus (MBH) and that GAD(67) mRNA levels decreased in the suprachiasmatic nucleus. In addition, we observed an age-related increase of oestrogen receptor (ER)alpha mRNA in the MBH, and both ERalpha and ERbeta mRNA expression was up-regulated in the pituitary of middle-aged rats compared to young animals. Taken together, our data support the existence of a male 'andropause' that is, like the menopause in females, accompanied by changes in neurotransmitter and hormone receptor expression that are involved in regulating the function of the GnRH pulse generator.


[Histological changes in the ligated vasa ovarica (author's transl)].
During gynecological operations 45 ligamenta infundibulopelvica were resected after 5 to 45 minutes. The intravascular changes of the ligated vasa ovarica were examinated. The histological examinations of the stumps showed, that the organism protects itself by formation of obstruction thrombi against a hemorrhage. The blood coagulation processes are local limited and the endothelial damages are causal important for the obstruction and obliteration.


Visual presentation of statistical concepts in diagnostic testing: the 2 × 2 diagram.
The purpose of this article is to present a visual conceptual framework for important statistical concepts in radiology, and to provide an online application to facilitate this visualization. Statistical measures such as sensitivity, specificity, and predictive values are ubiquitous in medical literature, yet thinking fluidly about these concepts is not always easy. The 2 × 2 diagram is a helpful guide.


Bilateral breast tumors, malignant phyllodes tumor and invasive lobular carcinoma in a 46,XX/46,XY mosaic female with family history of breast cancer.
Bilateral breast tumors, a malignant phyllodes tumor in the right breast and an invasive lobular carcinoma in the left breast, occurred in a 47-year-old woman with 46XX/46XY mosaic karyotype in her peripheral blood lymphocytes and intersex external genitalia. Postmortem examination revealed bilateral ovotestis. Three of the patient's sisters also had breast cancer. In situ hybridization with a Y-specific probe revealed Y-chromosome-specific signal in both tumors, suggesting that the clonal origin of tumors in this patient was Y-containing cells. Androgen-receptor polymorphism also revealed a monoallelic X chromosome pattern in the recurrent phyllodes tumor tissue taken at autopsy, in addition to loss of heterozygosity demonstrated at locus TP53. The slippage of the CA repeats in the tumor was also shown at the loci of D5S82 and D11S527. The mechanistic basis for the occurrence of bilateral malignant tumors of the breast, XX/XY mosaicism, and familial clustering of breast cancer is still unknown. The present study, however, suggests that the sex chromosome abnormality may have modified the cancer phenotype in a manner similar to breast cancer in Klinefelter's syndrome (though phenotypically male) and the Y chromosome may have promoted cell growth.


The Cell Fate Controlling CLE40 Peptide Requires CNGCs to Trigger Highly Localized Ca2+ Transients in Arabidopsis thaliana Root Meristems.
Communication between plant cells and their biotic environment largely depends on the function of plasma membrane localized receptor-like kinases (RLKs). Major players in this communication within root meristems are secreted peptides, including CLAVATA3/EMBRYO SURROUNDING REGION40 (CLE40). In the distal root meristem, CLE40 acts through the RLK ARABIDOPSIS CRINKLY4 (ACR4) and the leucine-rich repeat (LRR) RLK CLAVATA1 (CLV1) to promote cell differentiation. In the proximal meristem, CLE40 signaling requires the LRR receptor-like protein CLAVATA2 (CLV2) and the membrane localized pseudokinase CORYNE (CRN) and serves to inhibit cell differentiation. The molecular components that act immediately downstream of the CLE40-activated receptors are not yet known. Here, we show that active CLE40 signaling triggers the release of intracellular Ca2+ leading to increased cytosolic Ca2+ concentration ([Ca2+]cyt) in a small subset of proximal root meristem cells. This rise in [Ca2+]cyt depends on the CYCLIC NUCLEOTIDE GATED CHANNELS (CNGCs) 6 and 9 and on CLV1. The precise function of changes in [Ca2+]cyt is not yet known but might form a central part of a fine-tuned response to CLE40 peptide that serves to integrate root meristem growth with stem cell fate decisions and initiation of lateral root primordia.


Foxo3a-dependent Bim transcription protects mice from a high fat diet via inhibition of activation of the NLRP3 inflammasome by facilitating autophagy flux in Kupffer cells.
The role of Foxo3a in the regulation of autophagy flux and activation of the NLRP3 inflammasome in KCs suffering from HFD conditions is unknown. Up-regulation of Foxo3a restored autophagy flux and dampened the activation of the NLRP3 inflammasome in KCs stimulated with PA and LPS. In contrast, down-regulation of Foxo3a increased blockage of autophagy flux and promoted NLRP3 inflammasome activation. Additionally, mRNA levels of Bim were significantly changed with the alteration of Foxo3a in KCs under PA and LPS stimulation among foxo3a targeted genes. Overexpression of Bim restored autophagy influx and attenuated NLRP3 inflammasome pathway activation. In addition, autophagy formation was restored, and activation of NLRP3 inflammasome was inhibited in KCs isolated from mice treated with Iturin A and fed with a HFD. Autophagy flux in KCs and activation levels of NLRP3 inflammasome were evaluated after altering the expression of Foxo3a in KCs before stimulation with PA and LPS. Additionally, various target genes of Foxo3a were measured in KCs pretreated with an agonist (Iturin A) or inhibitor (SC97) of Foxo3a after KCs stimulation with PA and LPS in order to hunt for targets of Foxo3a. Activation levels of NLRP3 inflammasome in isolated KCs, as well as autophagy flux, were measured after mice were treated with Iturin A and fed with a HFD for 16 weeks. Foxo3a restores autophagy flux and attenuates the activation of the NLRP3 inflammasome by promoting the transcription of Bim, suggesting a potential therapeutic target in NAFLD and other obesity-related diseases.


A comparative analysis of the ability of five classes of pharmacological agents to augment skin flap survival in various models and species: an attempt to standardize skin flap research.
There is a myriad of research in the pharmacological manipulation of skin flap survival. However, skepticism exists as to whether any of these drugs is clinically useful. We evaluated the efficacy of five categories of agents in improving skin flap survival in five different rat flap models. Diltiazem, isoxsuprine hydrochloride, nitroglycerin, prazosin hydrochloride (two doses), and methyldopa were compared in a double-blind, randomized fashion. Their benefits were assessed in a musculocutaneous flap, axial flap, and three types of random flaps. The "best" drug was determined to be nitroglycerin. Its efficacy was verified in a primate model.


[Atrial fibrillation on the intensive care unit : The special prognostic importance of the first manifestation].
Atrial fibrillation (AF) is the most common arrhythmia in the intensive care unit (ICU) and is associated with increased mortality. The AF is classified into five different forms, initially diagnosed AF, paroxysmal AF, persistent AF, long-standing persistent AF and permanent AF. Studies could confirm that the first manifestation of AF (new onset AF) is of particular importance in intensive care patients. The mortality and costs are much higher than for patients with chronic AF. This important clinical difference of the AF pattern should be taken into consideration in the treatment of intensive care patients. The treatment of comorbidities is essential in the treatment concept on the ICU. In patients with an increased risk of thromboembolic complications, therapeutic anticoagulation is indicated, although the greatly increased risk of bleeding during intensive care treatment should be considered in individual cases. In cases of hemodynamic instability electrical cardioversion should immediately be carried out. Otherwise, pharmacological cardioversion can also be carried out. Apart from a few exceptions, amiodarone is the antiarrhythmic drug of choice for rhythm control due to the contraindications for other drugs.


Regulatory mechanisms of cutaneous delayed-type hypersensitivity. II. Suppression of cutaneous delayed-type hypersensitivity by macrophage disappearance reaction.
Studies were performed on the behavior of cutaneous delayed-type hypersensitivity (DTH) in guinea pigs in which macrophage disappearance reaction (MDR) was induced. Guinea pigs were immunized with dinitrophenylated egg albumin (DNP-EA), followed by intraperitoneal (ip) injection of liquid paraffin in order to elicit peritoneal macrophages. Subsequently 20 micrograms of EA was injected into these animals and the animals were divided into two groups. One group of animals was sacrificed for estimation of MDR 6 hr after the subsequent ip injection. The other group received a skin test by EA at the time of the subsequent ip injection. The first group of animals sacrificed for estimation of MDR exhibited a marked reduction in the number of peritoneal macrophages. The second group of animals that received skin tests revealed suppressed skin reactions 24 hr after the subsequent ip injection. A similar experiment was performed using the guinea pigs doubly immunized with DNP-EA and dinitrophenylated bovine gamma-globulin (DNP-BGG). Induction of MDR was performed by ip injection of BGG and skin tests were done by both EA and BGG. As a result, suppression of not only BGG-induced skin reactions but also EA-induced skin reactions was observed in animals in which MDR had been induced by BGG. In addition, the guinea pigs in which MDR was induced showed hyporeactivity to phytohemagglutinin (PHA). Reactivity to skin reactive factor (SRF) was also suppressed in these animals. The culture supernatants of macrophages incubated with the MIF fraction in vitro showed the ability to suppress skin reactions of cutaneous DTH, PHA and SRF.


Polyunsaturated thia- and oxa-fatty acids: incorporation into cell-lipids and their effects on arachidonic acid- and eicosanoid synthesis.
EPA, DHA, C15SCH2COOH (n-3), C15SCH2COOH (n-6) and C18SCH2COOH (n-3) are extensively incorporated into phospholipids and triacylglycerol in rat hepatocytes after 24 h incubation with 80 microM fatty acid/derivative. Only traces of polyunsaturated 3-oxa fatty acids (C15OCH2COOH, C18OCH2COOH) were incorporated. C15-S-butyric acid (n-3) is a stronger inhibitor of delta6-desaturase in rat liver-microsomes than C15SCH2COOH (n-3), C15-S-propionic acid (n-3), EPA and DHA. It inhibits delta5-desaturase in a similar manner to EPA and DHA. Arachidonic acid and C15SCH2COOH, (n-6) are better substrates for PGH-synthase than EPA and C15SCH2COOH, (n-3), showing the inhibitory effect of the n-3 bond. The n-3 polyunsaturated fatty acids, including the sulfur-substituted fatty acid derivatives, are poor substrates for PGH-synthase. However, they inactivate the PGH-synthase activity at least as efficiently as arachidonic acid. C15SCH2COOH (n-3), C15S(CH2)2COOH (n-3) and C18SCH2COOH (n-3) induce peroxisomal beta-oxidation more than EPA and DHA.


Preoxygenation: from hardcore physiology to the operating room.
If we define the human body by the mass of the elements that compose it, we could say that we are oxygen and other elements. Oxygen, in addition to being fundamental in our composition, is an element that we constantly need to support cellular respiration and, therefore, life. Interestingly, despite its importance, humans have not developed mechanisms that allow us to store it and, therefore, we are unable to sustain life if we are deprived of ventilation, even for brief periods. Accordingly, the ability to induce the cessation of ventilation in a patient must be accompanied by different technical and non-technical skills that allow the patient's safety to be maintained in this highly vulnerable state. Through the use of basic mathematical tools and comparative physiology, we hereby propose to review the physiological foundations of preoxygenation to understand the reasons behind the clinical recommendations in this field.


Fully automated 3D segmentation of MR-imaged calf muscle compartments: Neighborhood relationship enhanced fully convolutional network.
Automated segmentation of individual calf muscle compartments from 3D magnetic resonance (MR) images is essential for developing quantitative biomarkers for muscular disease progression and its prediction. Achieving clinically acceptable results is a challenging task due to large variations in muscle shape and MR appearance. In this paper, we present a novel fully convolutional network (FCN) that utilizes contextual information in a large neighborhood and embeds edge-aware constraints for individual calf muscle compartment segmentations. An encoder-decoder architecture is used to systematically enlarge convolution receptive field and preserve information at all resolutions. Edge positions derived from the FCN output muscle probability maps are explicitly regularized using kernel-based edge detection in an end-to-end optimization framework. Our method was evaluated on 40 T1-weighted MR images of 10 healthy and 30 diseased subjects by fourfold cross-validation. Mean DICE coefficients of 88.00-91.29% and mean absolute surface positioning errors of 1.04-1.66 mm were achieved for the five 3D muscle compartments.


Peptide coated gold nanoparticles that bind lanthanide ions.
Water soluble gold nanoparticles are coated with peptides bearing a dithiol surface active group for studies of lanthanide binding; characteristic red luminescence is observed upon europium binding to the nanoparticles.


Failure Analysis of Tension Clamps (SKL15) Used in Serviced Urban Railway Tracks: Numerical Analyses and Experiments.
In this study, the material properties of the damage-vulnerable parts and the residual strain of tension clamps comprising many curved parts, such as those used in urban railroads, were tested and analyzed. The effects of decreasing the strengths of the tension clamps on performance were then assessed. The permanent deformation characteristics of the tension clamps of aged specimens (6, 11, and 16 years of service) exhibited tendencies similar to the strain-hardening characteristics of the stress-strain responses reported in previous studies. As the service period increased, plastic deformation occurred in the middle bands of the tension clamps. When used for 16 years in urban railroads, the tension clamps underwent ~10% deformation compared with their initial shapes. Furthermore, based on laboratory tests, the deterioration levels of the tension clamps according to the service period were examined as functions of Young's modulus. Stress levels close to the yield strength occurred in the middle band of the tension clamp when the clamping force was introduced. As a results, it is possible to determine whether the clamping force confirms that decrease by using the Young's moduli of tension clamps, and the deterioration of the function and the replacement time of tension clamps that may occur during service can be predicted.


What Is the Evidence That Dietary Macronutrient Composition Influences Exercise Performance? A Narrative Review.
The introduction of the needle muscle biopsy technique in the 1960s allowed muscle tissue to be sampled from exercising humans for the first time. The finding that muscle glycogen content reached low levels at exhaustion suggested that the metabolic cause of fatigue during prolonged exercise had been discovered. A special pre-exercise diet that maximized pre-exercise muscle glycogen storage also increased time to fatigue during prolonged exercise. The logical conclusion was that the athlete's pre-exercise muscle glycogen content is the single most important acutely modifiable determinant of endurance capacity. Muscle biochemists proposed that skeletal muscle has an obligatory dependence on high rates of muscle glycogen/carbohydrate oxidation, especially during high intensity or prolonged exercise. Without this obligatory carbohydrate oxidation from muscle glycogen, optimum muscle metabolism cannot be sustained; fatigue develops and exercise performance is impaired. As plausible as this explanation may appear, it has never been proven. Here, I propose an alternate explanation. All the original studies overlooked one crucial finding, specifically that not only were muscle glycogen concentrations low at exhaustion in all trials, but hypoglycemia was also always present. Here, I provide the historical and modern evidence showing that the blood glucose concentration-reflecting the liver glycogen rather than the muscle glycogen content-is the homeostatically-regulated (protected) variable that drives the metabolic response to prolonged exercise. If this is so, nutritional interventions that enhance exercise performance, especially during prolonged exercise, will be those that assist the body in its efforts to maintain the blood glucose concentration within the normal range.


Assessment of cytotoxic T-lymphocyte phenotype using the specific markers granzyme B and TIA-1 in cervical neoplastic lesions.
Cervical carcinomas are closely associated with high-risk human papillomavirus (HPV) types and are preceded by cervical intraepithelial neoplasia (CIN). Most CIN lesions regress spontaneously and will not evolve to invasive carcinoma. The cellular immune system mediated by cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells are thought to play an important role in the ultimate decline of CIN lesions. Although TIA-1 is constitutively expressed in the majority of circulating T cells and defines a subpopulation of CD8+ T cells with cytotoxic potential, granzyme B is only expressed in CTLs upon activation. In the present study we have evaluated the expression of these proteins by lymphocytes present in 24 randomly chosen CIN lesions with increasing degree of atypia and in 14 cervical squamous cell carcinomas. As major histocompatibility complex (MHC) class I expression is frequently down-regulated in HPV-induced lesions, thus possibly frustrating tumour cell recognition by infiltrating CTLs, these lesions were also analysed for MHC class I expression. The results indicated that in most CIN lesions only a minority of CTLs are activated, whereas in some carcinomas a massive infiltration of activated, i.e. granzyme B-positive, CTLs were observed. The percentage of activated CTLs was not related to expression of MHC class I on neoplastic cells. These results suggest that in some carcinomas proper activation of CTLs occurs but that most likely local factors or immunoselection of resistant neoplastic cells inhibit a proper response of CTLs to these neoplastic cells.


Evaluation of LigaTie device for total lung lobectomy in small breed dogs - An ex vivo study.
This study aimed to evaluate an effectiveness of airway-sealing techniques used in total lung lobectomies in small dog breeds. Total lung lobectomies were performed on five canine cadavers weighing 2.5-8 kg. Airway-sealing techniques were performed on two randomly selected lobes per cadaver. The airway-sealing techniques consisted of traditional suture ligation, Endoloop, and LigaTie. After applying all surgical methods, bronchial stump was collected from the tongue and prepared. The effectiveness of each airway-sealing technique was evaluated by submerging the bronchial stumps in saline, followed by intubation to gradually increase the airway pressure to 80 cmH2O to identify the presence of air leakage in each lobe. Seven of the ten lobes in the traditional suture ligation group had a leakage; the leakages were fatal in three lobes. A single fatal leak occurred in the Endoloop group, while no leakage was noted in the LigaTie group. Therefore, the LigaTie technique had a higher statistical efficacy than the traditional suture ligation (p = 0.007). In conclusion, the LigaTie application reduced the incidence of air leakage following total lung lobectomies in small dog breeds.


Clinical practice guidelines for children with cancer presenting with fever to the emergency room.
Patients with febrile neutropenia (FN) may develop severe infection, septic shock, and death. To improve the outcome of pediatric oncology patients with suspected FN, clinical practice guidelines were developed for these patients at the emergency room (ER). The objective of the present study was to evaluate compliance of the clinical practice guidelines for children with cancer presenting with fever to the ER and adverse outcomes after using the guidelines. A retrospective cohort study was undertaken of children with cancer presenting with fever to the ER from January 2007 to December 2008 after the clinical guidelines were implemented. The control group was the children with cancer who presented with fever during January 2005-December 2006. Guideline compliance was evaluated by recording the time of initial clinical and laboratory assessment and door-to-antibiotic time. The adverse outcomes, including septic shock and death, were determined. There were 170 febrile episodes after using the guidelines. Approximately half (49.4%) of the patients received clinical assessment and laboratory results within 60 min, whereas the antibiotics were administered within 120 min in 80%. Prevalence of septic shock and intensive care unit admission were significantly reduced compared to controls (P = 0.011 and 0.016, respectively). No infection-associated mortality was found after the implementation of the guidelines. Using the clinical practice guidelines for pediatric oncology patients with fever was found to reduce the adverse outcomes and improve survival.


Experience of the endoscopist increases detection rates of smaller size and higher histological grade polyps.
Adenoma and polyp detection rates (ADR and PDR, respectively) are important indicators of endoscopy quality, particularly in colorectal carcinoma screening. To assess the influence of the endoscopist's experience on the ADR and PDR. In this study, 9635 colonoscopies were screened during a 5-year period. Only 5738 were finally analyzed due to exclusion criteria. The endoscopists were separated in three groups of experience according to the number of colonoscopies performed in the past (yearly and total). The number of polyps and adenomas, as well as the size and histology of these polyps were recorded. The ADR and PDR were similar regardless of the experience of the endoscopist, but those with more experience clearly found more polyps of less than 10 mm (P = 0.01) and of less than 3 mm (P < 0.0001). Most of the differences were due to a higher number of flat polyps detected by the experienced group. This study also shows that more experienced endoscopists detect adenomas with more advanced histology (P < 0.0001). Even though the ADR and PDR are similar in all groups of endoscopists, the less experienced endoscopists could be missing some of the smaller polyps, sometimes with more advanced histology.


Cardiorespiratory response to exercise after the Fontan operation: a serial study.
The purpose of this study was to assess whether there is deterioration of aerobic capacity over time after the Fontan operation in individual patients. We previously observed that maximal aerobic capacity after the Fontan operation was lower in older patients than in younger patients. It was unclear whether this represented a decrease in aerobic capacity with time after operation or was a function of studying patients of different ages at different times postoperatively. All patients who had more than one postoperative exercise study were included. There were 25 patients (19 male, 6 female), aged 3.8 to 39 years at the time of the operation. The first exercise test was performed, on average, 2.2 years after the Fontan operation, and the last exercise test was performed, on average, 5.9 years (range 1.8 to 13) after the operation. In 11 patients, coronary sinus drainage was left on the pulmonary venous side. Five patients had had a previous Glenn operation. Exercise was performed to exhaustion with use of a 3-min incremental cycle protocol. Exercise duration, oxygen uptake, blood pressure, respiratory rate, minute ventilation, pulmonary blood flow index, exercise factor, ST-T wave changes and the prevalence of arrhythmias were similar during the first and last tests. Exercise systemic arterial blood oxygen saturation decreased from the first to the last postoperative test (p < 0.006) regardless of age. The percent of predicted heart rate, at rest and during maximal exercise, decreased more in older patients from the first to the last test (p < 0.05 for rest and exercise). In this select group of patients, exercise tolerance remained relatively unchanged over the range of 13 years after the Fontan operation. Heart rate at rest and during maximal exercise decreased more than predicted for age in older patients. A small but significant progressive decrease in systemic arterial blood oxygen saturation was found. The former might represent abnormal sinus node function in patients with functional single ventricle, and the latter might represent a tendency toward development of abnormal ventilation/perfusion patterns resulting from the development of small pulmonary arteriovenous fistulas or an effect of position of the coronary sinus postoperatively.


Microbiological Quality of Deer Meat Treated with Essential Oil Litsea cubeba.
The present study aimed to evaluate deer meat microbiological quality when treated with essential oil (EO) from Litsea cubeba (dissolved in rapeseed oil at concentrations 0.5 and 1%), in combination with vacuum packaging during 20 days of storage of meat at 4 °C. Total viable counts (TVC), coliforms bacteria (CB), lactic acid bacteria (LAB) and Pseudomonas spp. were analysed at day 0, 1, 5, 10, 15 and 20. MALDI-TOF MS Biotyper technology was applied to identify microorganisms isolated from meat. The highest number of TVC at the end of the experiment was 5.50 log CFU/g in the aerobically packaged control group and the lowest number of TVC was 5.17 log CFU/g in the samples treated with 1.0% Litsea cubeba EO. CB were not detected in the samples treated with 1.0% Litsea cubeba EO during the entire storage period. Bacteria of the genus Pseudomonas were detected only in the aerobically and vacuum packaged control group. The highest number of LAB was 2.06 log CFU/g in the aerobic control group, and the lowest number of LAB was 2.01 log CFU/g in the samples treated with 1.0% Litsea cubeba EO on day 20. The most frequently isolated bacteria from deer meat were Pseudomonas ludensis, Pseudomonas corrugata, Pseudomonas fragi, Bacillus cereus, Staphylococcus epidermidis and Sphingomonas leidyi.


Activation of microglia in the brains of humans with heart disease and hypercholesterolemic rabbits.
Activated microglial cells are concentrated in senile plaques characteristic of Alzheimer's disease. Such accumulations of activated microglia may contribute towards neurodegeneration via production of cytokines and free radicals. Studies suggesting a link between Alzheimer's disease and heart disease led us to study microglia immunohistochemically, using monoclonal antibody LN-3, in age-matched nondemented humans with and without heart disease. Using a qualitative staging system for assessing morphological changes occurring in microglia, we found higher microglial activation in the brains of subjects with heart disease than in those without it. Lectin histochemical examination of brains from rabbits maintained on a high-cholesterol diet also revealed increased microglial activation and leukocyte infiltration. Collectively our observations from humans and rabbits suggest that hypercholesterolemia and heart disease accelerate brain aging, and that the formation of senile plaques may be the end result of progressive microglial activation that occurs with aging.


Association between lifestyle-related disorders and visceral fat mass in Japanese males: a hospital based cross-sectional study.
This study aimed to examine the association between lifestyle-related disorders and visceral fat mass, and to estimate an appropriate cutoff value for visceral fat mass that correlated with body mass index (BMI) and waist circumference (WC). This cross-sectional study was conducted between July 2012 and August 2013 at Bange Kosei General Hospital, in Fukushima, Japan. All study participants were adult males who had completed voluntary medical check-ups that included estimation of visceral fat mass by bioelectrical impedance analysis (BIA). Participants were without past histories of atherosclerotic complications or were not currently taking medications for lifestyle-related disorders. Multivariate analysis was performed to estimate the association between lifestyle-related disorders and quartiles of visceral fat mass. Of 536 total respondents, 442 were included in the analysis. Mean participant age was 56 years, and mean values of BMI, WC, and visceral fat mass were 24.1 kg/m(2), 85.9 cm, and 2.1 kg, respectively. Visceral fat mass ≥1.8 kg was positively associated with an increased prevalence of dyslipidemia, elevated blood pressure, and impaired glucose tolerance. Cutoff values that correlated with visceral fat mass (≥1.8 kg) were 85.3 cm for WC and 23.25 kg/m(2) for BMI. Visceral fat mass ≥1.8 kg was positively associated with lifestyle-related disorders and closely related to WC and BMI cutoff values used to diagnose obesity. BIA may be a useful method for assessing visceral fat mass, and these findings provide important evidence for the use of BIA in the early detection of central obesity for preventing lifestyle-related disorders.


Post-traumatic syndrome: another myth discredited.
Further studies confirm the authors' previous contention that patients suffering from the post-traumatic syndrome (PTS) do recover from this syndrome and return to full-time work before litigation is settled. Failure to have returned to work by the time of settlement indicates a bad prognosis, and such patients rarely return to work afterwards; the older the patient the worse the prognosis.


Novel eco-friendly spectrophotometric approaches for resolution of fixed dose formulation of phenylbutazone with minor component of dexamethasone: Greenness assessment by AGREE tool.
Spectrophotometric resolution of severely overlapped binary mixtures with minor component is challenging. Herein, coupling of mathematical manipulation steps with sample enrichment was conducted on the binary mixture spectrum of Phenylbutazone (PBZ) and Dexamethasone sodium phosphate (DEX) to resolve, for the first time each component separately. Simultaneous determination of both components in a mixture ratio of 1:0.002 was achieved in their zero or first order spectra by the recent factorized response method along with ratio subtraction and constant multiplication methods; all coupled with spectrum subtraction. In addition, a novel second derivative concentration value and second derivative constant value methods were developed for PBZ determination. The concentration of the minor component DEX was obtained, without preliminary separation steps by derivative ratio after sample enrichment by either spectrum addition or standard addition. Spectrum addition approach showed superior characteristics compared to standard addition technique. All proposed methods were placed through a comparative study. Linear correlation was found to be 1.5-18.0 µg/mL for PBZ, and 4.0-45.0 µg/mL for DEX. The proposed methods were validated in accordance with ICH guidelines. The greenness assessment of the proposed spectrophotometric methods was evaluated by AGREE software. Results obtained from the statistical data were evaluated by comparing to one another as well as the official USP methods. These methods offer a cost and time effective platform to analyze bulk materials and combined veterinary formulation.


Therapy of human ovarian carcinoma xenografts using doxorubicin encapsulated in sterically stabilized liposomes.
This study compared the therapeutic effects of doxorubicin hydrochloride in saline and in sterically stabilized, long-circulating liposomes composed of hydrogenated soy phosphatidylcholine/cholesterol/polyethylene glycol-distearoyl-phosphatidyl-ethanolamine (Doxil). The drug formulations were injected intravenously or intraperitoneally to treat the human ovarian carcinoma HEY, which was implanted subcutaneously or intraperitoneally into mature female Swiss nude mice. The long-circulating liposome formulation was significantly more effective than was the free drug in inhibiting tumor growth and in producing cure. The liposome formulation was significantly less toxic than was the free drug. This is the first demonstration of the therapeutic effectiveness of doxorubicin in sterically stabilized liposomes against human tumor xenografts. The encapsulation of doxorubicin in long-circulating liposomes significantly enhanced the therapeutic efficacy of the drug against a human ovarian carcinoma.


Cost-effectiveness analysis and HIV screening: the emergency medicine perspective.
Cost-effectiveness analysis is a useful tool for decisionmakers charged with prioritizing of the myriad medical interventions in the emergency department (ED). This analytic approach may be especially helpful for ranking programs that are competing for scarce resources while attempting to maximize net health benefits. In this article, we review the health economics literature on HIV screening in EDs and introduce the methods of cost-effectiveness analysis for medical interventions. We specifically describe the incremental cost-effectiveness ratio--its calculation, the derivation of ratio components, and the interpretation of these ratios.


Modes of biliobiliary anastomosis in relation to the healing process and occurrence of postoperative stricture.
The inverting and everting methods of biliobiliary anastomoses were compared histopathologically and electron microscopically. Epithelialization started on the 3rd postoperative day and occurred within 8 mm of the anastomosis with an earlier and more active epithelialization being seen in the proximal area than in the distal. A rapid decrease of the mucosal defect was seen for 3-5 days which slowed down thereafter, and closure was achieved by 30 days after the anastomosis in both groups. The everted group showed a smoother and more rapid healing process, quicker epithelialization, and less mucosal defects than the inverted group. In the chronic phase, the inverted group showed more papillary hyperplasia and more pronounced fibrosis of the wall. The stricture index, being the internal circumference of the common bile duct: proximal x 2/anastomosis site + duodenal x 100, of the everted group was 123.7% compared to 146.7% for the inverted group, but there was no statistical difference. There was no difference in the total area of crypts, representing the epithelialization, between the two groups. Anastomoses with proximal dilatation therefore healed more slowly than those without dilatation. These findings show everted anastomosis to be superior to inverted anastomosis and thus support the usefulness of T-tube drainage to prevent postoperative dilatation of the bile duct.


Polycyclic aromatic hydrocarbon (PAH) and metal contamination of air and surfaces exposed to combustion emissions during emergency fire suppression: Implications for firefighters' exposures.
This study examined occupational exposures of Ottawa firefighters to combustion by-products and selected metals. We measured exposures to polycyclic aromatic hydrocarbons (PAHs), antimony, cadmium, and lead using (1) personal air samplers worn by firefighters during emergency fire suppression; (2) wipe samples from skin, personal clothing, and personal protective equipment (PPE) collected before and after emergency firefighting (n = 29); and (3) air samples collected in three fire stations vehicle bays, truck cabs, and one administration office. We assessed OFS PPE decontamination procedures using wipe samples collected before and after laundering (n = 12). Air concentrations exceeded occupational exposure limits at two fire events for lead and nine for PAHs. After fire suppression, PAH concentrations were significantly higher on skin and PPE (p < 0.001), skin, clothing, and PPE for antimony (p < 0.001, 0.01, and 0.05, respectively), and skin and PPE for lead (p < 0.001). Air concentrations of PAHs and antimony were significantly higher in vehicle bays compared to the office (p < 0.05), but significantly lower compared to fire truck cabs (p < 0.05). Washing PPE was effective in removing, on average, 61% of PAHs, 55% of antimony, 97% of lead, and 90% of cadmium. These results indicate that firefighters are significantly exposed, via multiple routes, to combustion by-products during on-shift fire suppression.


RANK (receptor activator of nuclear factor-kappaB) and RANKL expression in multiple myeloma.
The new members of the tumour necrosis factor (TNF) receptor-ligand family, receptor activator of nuclear factor-kappaB ligand (RANKL) and its receptor RANK, play a crucial role in osteoclast differentiation and activation. An increased expression of RANKL and/or RANK may be involved in the excessive bone resorption observed in multiple myeloma (MM). We used immunohistochemistry to study RANK and RANKL expression in bone marrow (BM) biopsies obtained at diagnosis in 15 MM patients, six patients with monoclonal gammopathy of undetermined significance (MGUS) and 10 normal BM biopsies. Plasma cells were not labelled with anti-RANKL or anti-RANK antibodies. In all biopsies, RANKL was expressed in endosteal bone surface, around vessels and in cells characterized by cytoplasmic expansions. These last cells did not express CD45 and were vimentin positive, corresponding to bone marrow stromal cells. Numerous stromal cells expressed RANKL in MM and MGUS specimens, with a greater expression in MM than in MGUS. Very few cells were stained with anti-RANKL in normal BM specimens. With the anti-RANK antibody, small mononuclear cells in the bone microenvironment were positive and were identified as erythroblast cells. In conclusion, we showed that RANKL was expressed in reticular stromal cells, with a greater intensity in myeloma specimens. These results suggest that RANKL overexpressed by bone marrow stromal cells may contribute to the high rate of bone resorption observed in MM.


Early-life lead exposure and neurodevelopmental disorders.
Lead (Pb2+) exposure is a global public health problem of major proportion with an alarming number of children with blood Pb2+ levels > 10 >g/dL, twice the current CDC reference level for Pb2+ exposure. Mounting evidence from population-based studies suggests an association between chronic early life Pb2+ exposure (CELLE) and psychiatric disorders, specifically schizophrenia (SZ). Preclinical studies suggest a common mechanism in the pathophysiology of CELLE and SZ, NMDA receptor hypofunction. Here we describe human and experimental animal studies providing the evidence for such an association. Further, recent preclinical studies indicate that Pb2+-induced changes in neurotransmitter receptors that mediate the action(s) of drugs of abuse are increased in brain regions associated with addiction circuits in adolescence, a period of increased susceptibility to drug use and abuse and expression of psychiatric disease in humans. In summary, the relationship between the global burden of childhood Pb2+ exposure and the latent onset of psychiatric disorders and predisposition to drug use requires further investigations in human populations.


Diaqua-[3,5-bis-(4-pyrid-yl)-1H-1,2,4-triazole-κN](pyridine-2,6-dicarboxyl-ato-κO,N,O)nickel(II).
In the title compound, [Ni(C(7)H(3)NO(4))(C(12)H(9)N(5))(H(2)O)(2)], the Ni(II) atom is coordinated in a distorted octa-hedral geometry by one N and two O atoms from a pyridine-2,6-dicarboxyl-ate ligand, one N atom from a 3,5-bis-(4-pyrid-yl)-1H-1,2,4-triazole ligand in equatorial positions and two water mol-ecules in axial positions. The crystal packing is consolidated by inter-molecular O-H⋯O, O-H⋯N and N-H⋯O hydrogen bonds.


Pelvic exenteration for recurrent or persistent cervical cancer: experience of five years at the National Cancer Institute in Mexico.
Cervical cancer constitutes a major health problem in Mexico and other developing countries. The purpose of our study was to assess the experience of a comprehensive national oncological reference center on pelvic exenteration for post-radiotherapy recurrent or persistent cervical cancer, describing the prognostic value of time to recurrence, procedure complications, and survival. Medical records from 42 patients with post-radiotherapy recurrent or persistent cervical cancer who underwent a pelvic exenteration with curative purposes from 1984 to 1989 were retrospectively reviewed. Histological diagnoses were squamous cell carcinoma (32 patients), adenosquamous carcinoma (9 patients), and adenocarcinoma (1 patient). Average follow up was of 56.3 mo after the procedure and global survival at 5 yr was 65.8%. Survival for patients with early recurrence was 56.9% vs 78% for patients with late recurrence (p = 0.05). Complications were observed in 65.3% of the cases with a surgical mortality of 4.8%. Pelvic exenteration is a surgical procedure with high morbidity in spite of the recent medical advances. Pelvic exenteration should not be indicated with palliative purposes owing to the high rate of complications. Patients with tumor persistence or early recurrence have a worse prognosis. In well-selected cases, exenteration may provide a survival benefit.


Complexation of Al(III) with reduced glutathione in acidic aqueous solutions.
The complexation of reduced glutathione (GSH) in its free and Al(III)-bound species in acidic aqueous solutions was characterized by means of multi-analytical techniques: pH-potentiometry, multinuclear ((1)H, (13)C and (27)Al) and two-dimensional nuclear Overhauser enhancement NMR spectroscopy ((1)H, (1)H-NOESY), electrospray mass spectroscopy (ESI-MS), and ab initio electronic structure calculations. The following results were found. In the 25 degrees C 0.1M KCl and 37 degrees C 0.15M NaCl ionic medium systems, Al(3+) coordinates with the important biomolecule GSH through carboxylate groups to form various mononuclear 1:1 (AlHL, AlH(2)L and AlH(-1)L), 1:2 (AlL(2)) complexes, and dinuclear (Al(2)H(5)L(2)) species, where H(4)L(+) denotes totally protonated GSH. Besides the monodentate complexes through carboxylate groups, the amino groups and the peptide bond imino and carbonyl groups may also be involved in binding with Al(3+) in the bidentate and tridentate complexes. The present data reinforce that the glycine carboxylate group of GSH has a higher microscopic complex formation constant than gamma-glutamyl carboxylate. Compared with simple amino acids, the tripeptide GSH displays a greater affinity for the Al(3+) ion and thus may interfere with aluminum's biological role more significantly.


Krüppel-like factor 8 is a novel androgen receptor co-activator in human prostate cancer.
Krüppel-like factor 8 (KLF8) plays important roles in cell cycle and oncogenic transformation. On other hand, androgen receptor (AR) is crucial in development of both androgen-dependent and independent prostatic malignancies. The aim of this study is to investigate the role of KLF8 in prostate cancer (PCa) and the relationship between KLF8 and AR. Eight human PCa cell lines, including androgen-dependent LNCap cells and androgen-independent 22Rv1 cells, as well as human PCa samples were studied. LNCap cells and 22Rv1 cells were transfected with plasmids encoding full-length wild-type KLF8 or KLF8 shRNA. The expression of KLF8 protein was detected using Western blotting or immunohistochemical staining. Cell proliferation in vitro was measured with MTT assay, and in vivo in a xenograft nude mouse model. Yeast two-hybrid screening, co-immunoprecipitation and pull down assays were used to examine the binding of KLF8 to AR. Luciferase reporter gene assay was used to measure the transcriptional activity of the genes targeted by AR. In 133 human PCa samples, KLF8 protein staining was observed in 92.65% (63/68) of high-grade PCa, 66.15% (43/65) of low-grade PCa, and 6.82% (3/44) of adjacent normal tissues. The expression of KLF8 was significantly associated with poorer overall survival. Overexpression of KLF8 enhanced the proliferation of both LNCap and 22Rv1 cells, while knockdown of endogenous KLF8 suppressed the proliferation. These manipulations exerted similar effects on the tumor volumes in the xenograft nude mouse model. Yeast two-hybrid screening revealed that KLF8 was a novel AR-interacting protein. With pull down assay and co-immunoprecipitation assay, we demonstrated that KLF8 bound directly to AR, and KLF8 enhanced AR target gene transcription. The results demonstrate that KLF8 is a novel AR transcriptional co-activator that is overexpressed in PCa and may play a role in progression of hormone-refractory PCa.


Advanced oxidation processes for water purification using percarbonate: Insights into oxidation mechanisms, challenges, and enhancing strategies.
Percarbonate (SPC) has drawn considerable attention due to its merits in the safety of handling and transport, stability, and price as well as environmental friendliness, which has been extensively applied in advanced oxidation processes (AOPs) for water decontamination. Nevertheless, comprehensive information on the application of SPC-AOPs for the treatment of organic compounds in aquatic media is scarce. Hence, the focus of this review is to shed light on the mechanisms of reactive oxygen species (ROS) evolution in typical SPC-AOPs (i.e., Fenton-like oxidation, photo-assisted oxidation, and discharge plasma-involved oxidation processes). These SPC-AOPs enable the formation of multiple reactive species like hydroxyl radical (•OH), superoxide radical (O2•-), singlet oxygen (1O2), carbonate radicals (CO3•-), and peroxymonocarbonate (HCO4-), which together or solely contribute to the degradation of target pollutants. Simultaneously, the potential challenges in practical applications of SPC-AOPs are systematically discussed, which include the influence of water quality parameters, cost-effectiveness, available active sites, feasible activation approaches, and ecotoxicity. Subsequently, enhancing strategies to improve the feasibility of SPC-AOPs in the practical implementation are tentatively proposed, which can be achieved by introducing reducing and chelating agents, developing novel activation approaches, designing multiple integrated oxidation processes, as well as alleviating the toxicity after SPC-AOPs treatment. Accordingly, future perspectives and research gaps in SPC-AOPs are elucidated. This review will hopefully offer valuable viewpoints and promote the future development of SPC-AOPs for actual water purification.


Features of non-insulin-dependent diabetes mellitus (NIDDM) in the Sudan.
413 NIDDM Sudanese patients were studied. The patients' ages at the onset of diabetes ranged from 20-72 years, with the majority of patients (44%) developing diabetes at the age between 40-50 years. Female to male ratio was 1.9:1. 46.2% of patients were obese and a family history of first degree relatives was obtained in 63% of patients. Complications of diabetes in this study were as follows: Neuropathy (31.5%), retinopathy (17.4%), cataract (16%), nephropathy (9.2%), coronary heart disease (5.1%), cerebrovascular disease (4.4%) and peripheral vascular disease (3.4%). Microangiopathic complications of diabetes were significantly related to the duration of diabetes and the degree of hyperglycaemia (P less than 0.001 using chi 2 test). Macroangiopathic complications were significantly related to aging and hyperglycaemia. Patients with good metabolic control (blood glucose less than 160 mg%) had less prevalence of complications than uncontrolled patients. We conclude that NIDDM is a common type of diabetes in our diabetic clinic. It is a disease with severe complications and morbidity and needs more attention regarding metabolic control, since good control reduces the prevalence of diabetic complications.


Clinical characteristics and severity prediction score of Adenovirus pneumonia in immunocompetent adult.
Compared with children and immunocompromised patients, Adenovirus pneumonia in immunocompetent adults is less common. Evaluation of the applicability of severity score in predicting intensive care unit (ICU) admission of Adenovirus pneumonia is limited. We retrospectively reviewed 50 Adenovirus pneumonia inpatients in Xiangtan Central Hospital from 2018 to 2020. Hospitalized patients with no pneumonia or immunosuppression were excluded. Clinical characteristics and chest image at the admission of all patients were collected. Severity scores, including Pneumonia severity index (PSI), CURB-65, SMART-COP, and PaO2/FiO2 combined lymphocyte were evaluated to compare the performance of ICU admission. Fifty inpatients with Adenovirus pneumonia were selected, 27 (54%) non-ICU and 23 (46%) ICU. Most patients were men (40 [80.00%]). Age median was 46.0 (IQR 31.0-56.0). Patients who required ICU care (n = 23) were more likely to report dyspnea (13[56.52%] vs 6[22.22%]; P = 0.002) and have lower transcutaneous oxygen saturation ([90% (IQR, 90-96), 95% (IQR, 93-96)]; P = 0.032). 76% (38/50) of patients had bilateral parenchymal abnormalities, including 91.30% (21/23) of ICU patients and 62.96% (17/27) of non-ICU patients. 23 Adenovirus pneumonia patients had bacterial infections, 17 had other viruses, and 5 had fungi. Coinfection with virus was more common in non-ICU patients than ICU patients (13[48.15%]VS 4[17.39%], P = 0.024), while bacteria and fungi not. SMART-COP exhibited the best ICU admission evaluation performance in Adenovirus pneumonia patients (AUC = 0.873, p < 0.001) and distributed similar in coinfections and no coinfections (p = 0.26). In summary, Adenovirus pneumonia is not uncommon in immunocompetent adult patients who are susceptible to coinfection with other etiological illnesses. The initial SMART-COP score is still a reliable and valuable predictor of ICU admission in non-immunocompromised adult inpatients with adenovirus pneumonia.


Reduction in cortical IMP-SPET tracer uptake with recent cigarette consumption in a young group of healthy males. San Diego HIV Neurobehavioral Research Center.
Functional brain imaging techniques are being used increasingly to infer disturbances in brain function in various neuropsychiatric disorders, but the specificity of such findings is not always clear. We retrospectively examined the effects of one possible confound - cigarette smoking - on cortical uptake of iodine-123 iodoamphetamine (IMP) using single-photon emission tomographic imaging in a young (mean age=35 years) healthy group of male controls divided according to their smoking history. Subjects who had never smoked (n=17), or those with a history of smoking but no recent smoking (n=8), had equivalent and significantly higher mean cortical uptake of IMP than subjects with a history of smoking and who were current smokers (n=8). There were no differences in the cortical distribution of IMP. Our results indicate that cigarette smoking has an acute effect on global cerebral blood flow. This potential confound must be considered before abnormalities in cortical tracer uptake are attributed to some neuropsychiatric disorder of interest.