Efficacy of the Gelstix nucleus augmentation device for the treatment of chronic discogenic low back pain: protocol for a randomised, sham-controlled, double-blind, multicentre trial.
Discogenic pain is the cause of pain in 26%-40% of patients with for low back pain. Consensus about treatment of chronic discogenic low back pain is lacking and most treatment alternatives are supported by limited evidence. The percutaneous implantation of hydrogels into the nucleus pulposus represents a promising regenerative intradiscal therapy. The hydrogel 'GelStix' is composed primarily of hydrolyzed polyacrylonitrile and acts as a reservoir of hydration, producing increased pressure and improved pH balance, potentially leading to disc preservation. We hypothesise that treatment with GelStix will lead to greater reduction in pain intensity at 6 months post-treatment compared with patients receiving sham treatment. This is a parallel group, randomised sham-controlled double-blind, multicentre trial to assess whether the GelStix device is superior to sham in reducing pain intensity in patients with chronic discogenic low back pain. The study will be conducted in two regional hospitals in Europe. Seventy-two participants will be randomised in a 1:1 ratio. The primary outcome will be the change in pain intensity between preoperative baseline and at 6 months postintervention. Secondary outcomes were disability, quality of life, the patient's global impression of change scale, the use of pain medication and the disc degeneration process assessed by means of MRI. For change in pain intensity, disability, health-related quality of life and disc height, mean values will be compared between groups using linear regression analysis, adjusted for treatment centre. Ethics approval was obtained from the Ethics Committee of the Canton Ticino, Switzerland (CE2982) and by the Medical Ethical Committee Arnhem-Nijmegen, the Netherlands (2016-2944). All patients that agree to participate will be asked to sign an informed consent form. Results will be disseminated through international publications in peer-reviewed journals, in addition to international conference presentations. NCT02763956. 7.1, 18 November 2020.


An AIDS-denialist online community on a Russian social networking service: patterns of interactions with newcomers and rhetorical strategies of persuasion.
The rise of social media proved to be a fertile ground for the expansion of the acquired immune deficiency syndrome (AIDS)-denialist movement (in the form of online communities). While there is substantial literature devoted to disproving AIDS-denialist views, there is a lack of studies exploring AIDS-denialists online communities that interact with an external environment. We explored three research areas: (1) reasons for newcomers to come to an AIDS-denialist community, (2) the patterns of interactions of the community with the newcomers, and (3) rhetorical strategies that denialists use for persuasion in the veracity of their views. We studied the largest AIDS-denialist community on one of the most popular social networking services in Russia. We used netnography as a method for collecting data for qualitative analysis and observed the community for 9 months (at least 2-3 times a week). While doing netnography, we periodically downloaded community discussions. In total, we downloaded 4821 posts and comments for analysis. Grounded theory approach was used for data analysis. Most users came to the community for the following reasons: their stories did not fit the unitary picture of AIDS disease progression translated by popular medical discourse, health problems, concern about HIV-positive tests, and desire to dissuade community members from false AIDS beliefs. On the basis of strength in AIDS-denialist beliefs, we constructed a typology of the newcomers consisting of three ideal-typical groups: (1) convinced: those who already had become denialists before coming to the group, (2) doubters: those who were undecided about the truth of either human immunodeficiency virus (HIV) science theory or AIDS-denialist theory, and (3) orthodox: those who openly held HIV science views. Reception of a newcomer mainly depended on the newcomer's belief status. Reception was very warm for the convinced, cold or slightly hostile for the doubters, and extremely hostile or derisive for the orthodox. We identified seven main rhetorical strategies of persuasion used by the denialists on the "undecided". Contrary to the widespread public health depiction of AIDS denialists as totally irrational, our study suggests that some of those who become AIDS denialists have sufficiently reasonable grounds to suspect that "something is wrong" with scientific theory, because their personal experience contradicts the unitary picture of AIDS disease progression. Odd and inexplicable practices of some AIDS centers only fuel these people's suspicions. We can conclude that public health practitioners' practices may play a role in generating AIDS-denialist sentiments. In interactions with the newcomers, the experienced community members highlighted the importance of personal autonomy and freedom of choice in decision making consistent with the consumerist ideology of health care. The study findings suggest that health care workers should change a one-size-fits-all mode of counseling for a more complex and patient-tailored approach, allowing for diversity of disease progression scenarios and scientific uncertainty.


Transfer for primary angioplasty versus immediate thrombolysis in acute myocardial infarction: a meta-analysis.
The benefit of primary percutaneous coronary intervention (PCI) over thrombolysis has been clearly demonstrated in acute myocardial infarction (AMI). However, the best therapeutic strategy for a patient with AMI presenting to acute care services without catheterization facilities remains under debate. Our objective was to gather all available information from clinical trials comparing transfer of patients experiencing AMI for angioplasty versus immediate thrombolysis. We performed a meta-analysis of all data available from published randomized trials and from presentations in scientific sessions of major cardiology congresses comparing the 2 strategies. The primary end point was the combined criteria (CC) of death/reinfarction/stroke as defined in each trial. Relative risk (RR) evaluated the treatment effect. We identified 6 clinical trials including 3750 patients. Transfer time was always <3 hours. The CC was significantly reduced by 42% (95% confidence interval [CI] 29% to 53%, P<0.001) in the group transferred for primary PCI compared with the group receiving on-site thrombolysis. When CC parameters were considered separately, reinfarction was significantly reduced by 68% (95% CI, 34% to 84%; P<0.001) and stroke by 56% (95% CI, -15% to 77%; P=0.015). There was a trend toward reduction in all-cause mortality of 19% (95% CI, -3% to 36%; P=0.08) with transfer for PCI. Even when transfer to an angioplasty center is necessary, primary PCI remains superior to immediate thrombolysis. Organization of ambulance systems, prehospital management, and adequate PCI capacity appear now to be the key issues in providing reperfusion therapy for AMI.


Note: Broadband low-noise photodetector for Pound-Drever-Hall laser stabilization.
The Pound-Drever-Hall laser stabilization technique requires a fast, low-noise photodetector. We present a simple photodetector design that uses a transformer as an intermediary between a photodiode and cascaded low-noise radio-frequency amplifiers. Our implementation using a silicon photodiode yields a detector with 50 MHz bandwidth, gain >10(5) V/A, and input current noise <4 pA/Hz, allowing us to obtain shot-noise-limited performance with low optical power.


Associations between central pulse pressure, microvascular endothelial function, and fluid overload in peritoneal dialysis patients.
Microcirculatory endothelial dysfunction is a complex phenomenon that contributes to the development of cardiovascular disease. However, the relationship between microcirculatory endothelial dysfunction and macrovascular disease remains incompletely understood. Fluid overload is a risk factor for cardiovascular mortality in patients undergoing peritoneal dialysis. Therefore, we investigated the effects of chronic fluid overload on both the microcirculation and macrocirculation in these patients. Thirty patients undergoing peritoneal dialysis were included in this cross-sectional study. We measured their central blood pressure and pulse wave velocity, assessed their microvascular endothelial function using drug-induced iontophoresis with laser Doppler flowmetry, and determined the amount of fluid overload using bioimpedance. We conducted a Spearman correlation analysis, univariate analysis, and stepwise multivariate regression models to determine the associations among the hemodynamic parameters. Acetylcholine-induced iontophoresis with laser Doppler flowmetry showed a correlation with both brachial and central pulse pressure (PP), but not with pulse wave velocity. Fluid overload was associated with both central and brachial PP and remained an independent predictor of central PP even after adjusting for multiple factors. However, fluid overload was not associated with microcirculatory endothelial function. In peritoneal dialysis patients, we observed a significant association between central PP and microvascular endothelial function, indicating a connection between macrocirculation and microcirculation. However, conclusive evidence regarding fluid overload as a mediator between these circulatory systems is lacking. Further research is needed to investigate this relationship.


Translation and validation of the Hong Kong Chinese version of the breastfeeding self-efficacy scale-short form.
Healthcare providers do not have a validated instrument to measure breastfeeding self-efficacy among Hong Kong Chinese. In this study, we sought to translate the breastfeeding self-efficacy scale-short form (BSES-SF) into Hong Kong Chinese and to examine the psychometric properties in a sample of 185 breastfeeding mothers. The construct validity of the translated scale was supported by confirmatory factor analysis and known group analysis. The receiver operating characteristics analysis indicated that the total score of the translated scale at 48-72 hours after delivery could be a useful diagnostic tool for identifying mothers likely to discontinue breastfeeding prematurely, before 6 months postpartum. Further research to cross-validate the suggested cut-off value of the scale is recommended.


Improving physician and medical student education in substance use disorders.
Medical and psychosocial problems related to substance use disorders (SUDs) remain a major source of national morbidity and mortality. This situation exists despite greater understanding of genetic, neurobiologic, and social underpinnings of the development of these illnesses that has resulted in many advances in addiction medicine. The value of assessment and brief intervention of this disease is well documented. Patients need to be identified and engaged in order for them to be treated. A variety of evidence-based pharmacologic and psychotherapeutic treatments are now available. Strong evidence exists that treatment of patients for SUDs produces results similar to or better than those obtained from treatment for other chronic illnesses. It is also clear that physicians can play a pivotal role in helping to reduce the burden of disease related to SUDs However, to do this, physicians need to be better educated. Through such education comes greater confidence in identification and providing treatment. Also, the discomfort and stigma often associated with this disease are reduced. The federal government-through the Office of National Drug Control Policy, the Surgeon General, the Center for Substance Abuse Treatment, the National Institute on Drug Abuse, the National Institute on Alcohol Abuse and Alcoholism, and the National Highway Traffic Safety Administration of the Department of Transportation (DOT)-is expending concerted efforts to improve physician education in addiction medicine. These efforts culminated in the Second Leadership Conference on Medical Education in Substance Abuse in December 2006. The osteopathic medical profession was represented at this conference. This article reviews not only the recommendations from this meeting, but also the nature of the problem, how members of the osteopathic medical profession are currently addressing it, and a strategy for improvement endorsed by the American Osteopathic Academy of Addiction Medicine.


The use of a standardized order set reduces systemic corticosteroid dose and length of stay for individuals hospitalized with acute exacerbations of COPD: a cohort study.
Systemic corticosteroids (SC) are an integral part of managing acute exacerbations of COPD (AECOPD). However, the optimal dose and duration vary widely in clinical practice. We hypothesized that the use of a "PowerPlan" order set in the electronic health system (EHS) that includes a 5-day SC order would be associated with a reduced steroid dose and length of stay (LOS) for individuals hospitalized with AECOPD. We conducted a retrospective cohort study of Medicare recipients discharged with an AECOPD diagnosis from our University Hospital from 2014 to 2016. Our EHS-based "COPD PowerPlan" order set included admission, laboratory, pharmacy, and radiology orders for managing AECOPD. The default SC option included intravenous methyl-prednisolone for 24 hours followed by oral prednisone for 4 days. The primary endpoint was the difference in cumulative steroid dose between the PowerPlan and the usual care group. Secondary endpoints included hospital LOS and readmission rates. The 250 patients included for analysis were 62±11 years old, 58% male, with an FEV1 55.1%±23.6% predicted. The PowerPlan was used in 72 (29%) patients. Cumulative steroid use was decreased by 31% in the PowerPlan group (420±224 vs 611±462 mg, P<0.001) when compared with usual care. PowerPlan use was independently associated with decreased LOS (3 days; IQR 2-4 days vs 4 days; IQR 3-6 days, P=0.022) without affecting 30- and 90-day readmission rates. Use of a standardized EHS-based order set to manage AECOPD was associated with a reduction in steroid dose and hospital LOS.


Current trends in the treatment of HR+/HER2+ breast cancer.
Treatment for HR+/HER2+ patients has been debated, as some tumors within this luminal HER2+ subtype behave like luminal A cancers, whereas others behave like non-luminal HER2+ breast cancers. Recent research and clinical trials have revealed that a combination of hormone and targeted anti-HER2 approaches without chemotherapy provides long-term disease control for at least some HR+/HER2+ patients. Novel anti-HER2 therapies, including neratinib and trastuzumab emtansine, and new agents that are effective in HR+ cancers, including the next generation of oral selective estrogen receptor downregulators/degraders and CDK4/6 inhibitors such as palbociclib, are now being evaluated in combination. This review discusses current trials and results from previous studies that will provide the basis for current recommendations on how to treat newly diagnosed patients with HR+/HER2+ disease.


Three Birds with One Stone: An Integrated Cathode-Electrolyte Structure for High-Performance Solid-State Lithium-Oxygen Batteries.
Constructing solid-state lithium-oxygen batteries (SSLOBs) holds a great promise to solve the safety and stability bottlenecks faced by lithium-oxygen batteries (LOBs) with volatile and flammable organic liquid electrolytes. However, the realization of high-performance SSLOBs is full of challenges due to the poor ionic conductivity of solid electrolytes, large interfacial resistance, and limited reaction sites of cathodes. Here, a flexible integrated cathode-electrolyte structure (ICES) is designed to enable the tight connection between the cathode and electrolyte through supporting them on a 3D SiO2 nanofibers (NFs) framework. The intimate cathode-electrolyte structure and the porous SiO2 NFs scaffold combination are favorable for decreasing interfacial resistance and increasing reaction sites. Moreover, the 3D SiO2 NFs framework can also behave as an efficient inorganic filler to enhance the ionic conductivity of the solid polymer electrolyte and its ability to inhibit lithium dendrite growth. As a result, the elaborately designed ICES can simultaneously tackle the issues that limit the performance liberation of SSLOBs, making the batteries deliver a high discharge capacity and a long lifetime of 145 cycles with a cycling capacity of 1000 mAh g-1 at 60 °C, much superior to coventional SSLOBs (50 cycles).


Vincamine exerts protective effect on spiral ganglion neurons in endolymphatic hydrops guinea pig models.
The aim of this study was to investigate the protective effects of vincamine in endolymphatic hydrops (ELH). After ELH guinea pigs treated by vincamine, the concentration of VAP in plasma, and the levels of cAMP, MDA, SOD, GSH-Px in right cochlea were measured using spectrophotometric method. The V2R, NMDAR1, p-NMDAR1, AQP2, p-AQP2, caspase3/9 and c-caspase3/9 expressions in right cochlea were detected using western blot analysis. The cochlear hydrops degree and SGNs density were evaluated by hemotoxylin and eosin staining (HE) test. Normal hearing and vestibular function were warranted by the tests of auditory brainstem response (ABR) and electronystagmography (ENG). After glutamate-injured SGNs treated with vincamine, the MDA, SOD GSH-Px, NGF, BDNF, NT3, NT4 and Trks levels were measured. Meanwhile, the Bcl2, Bax, NMDAR1, p-NMDAR1, PI3K, p-PI3K, Akt, p-Akt, caspase3/9 and cleaved-caspase3/9 expression levels were detected. Furthermore, the viability, apoptosis and necrosis of SGNs were tested by MTT and Hoechst/PI staining methods. The results indicated that vincamine could significantly inhibit the expression levels of cAMP, MDA, V2R, p-NMDAR1, p-AQP2 and c-caspase-3/-9 in cochlea, alleviate the cochlear hydrops degree, regulate the audiological and vestibular dysfunctions. The SGNs density, SOD and GSH-Px levels were also increased by vincamine. In vincamine-treating groups, the MDA, Bax, p-NMDAR1, and c-caspase3/9 levels were observably decreased, while SGNs survival, SOD, GSH, NGF, BDNF, NT3, NT4, Trks, Bcl2, p-PI3K, p-Akt expressions were improved. The present study indicated a novel use of vincamine in suppressing ELH formation by down-regulating the VAP/AQP2 signaling pathway. It also manifested that vincamine exerted protective effects on hearing via improving neurotrophin-dependent PI3K/Akt signaling pathway in SGNs.


Serum beta 2-microglobulin in acute and chronic leukaemia.
The serum concentration of beta 2-microglobulin (beta 2-m) was measured in 69 patients with acute or chronic lympho- and myeloproliferative disorders. Serum beta 2-m was found significantly increased in 12 out of 14 patients with chronic lymphatic leukaemia. The serum concentration was proportional to the estimated lymphatic infiltration of tissues but inversely related to the number of circulating lymphocytes. Cytostatic treatment was followed by a decrease in serum beta 2-m, but normalization of the serum concentration was not observed. 11 patients with chronic granulocytic leukaemia all had significantly elevated serum concentrations of beta 2-m and increased serum concentrations were also found in patients with acute leukaemias. Thus, 12 out of 25 patients with acute myeloid leukaemia and all of 5 patients with acute myelomonocytic leukaemia as well as 4 out of 5 patients with acute lymphatic leukaemia had increased serum beta 2-m levels. In acute leukaemia no correlation could be demonstrated between the blood lymphocyte concentration and serum beta 2-m. Also no significant changes in serum beta 2-m were found in either remission or relapse of the acute leukaemia. It is concluded that serum beta 2-m in patients with chronic leukaemia may reflect the total amount or turn-over of leukaemic cells in the body and that repeated determinations of serum beta 2-m in these patients might be useful as an estimate of the residual leukaemic cell mass after therapy. Apart from this the determination of serum beta 2-m seems to be of little, if any, clinical use in leukaemia.


Actuarial status of the OASI and DI Trust Funds.
This article summarizes the current financial and actuarial status of the Old-Age, Survivors, and Disability Insurance (OASDI) program. The results presented are from the 1984 Trustees Report and are similar to the results in the 1983 report. This year's estimates show that the Social Security Amendments of 1983 restored the financial soundness of the OASDI program. According to the actuarial estimates, benefits can be paid on time throughout the 1980's and for many years thereafter. Because trust fund levels are projected to be relatively low through 1987, however, the program could again experience financial difficulties in the near future if economic conditions become worse than anticipated under the pessimistic (Alternative III) assumptions. After 1987, the program's ability to withstand economic downturns is projected to improve. On the basis of intermediate (Alternative II-B) assumptions, the OASDI program is in long-range close actuarial balance. This actuarial balance reflects substantial year-by-year surpluses during the first half of the 75-year projection period that are slightly out-weighed by substantial deficits later on.


Iodine fortification may influence the age-related change in thyroid volume: a longitudinal population-based study (DanThyr).
To assess the individuals' thyroid volume changes after the mandatory nationwide iodine fortification (IF) program in two Danish areas with different iodine intake at baseline (Copenhagen, mild iodine deficiency (ID) and Aalborg, moderate ID). A longitudinal population-based study (DanThyr). We examined 2465 adults before (1997) and after (2008) the Danish IF of salt (2000). Ultrasonography was carried out by the same sonographers using the same equipment, after controlling performances. Participants treated for thyroid disease were excluded from analyses. Overall, median thyroid volume had increased in Copenhagen (11.8-12.2 ml, P=0.001) and decreased in Aalborg, although not significantly (13.3-13.1 ml, P=0.07) during the 11 years of follow-up. In both regions, there was an age-related trend in individual changes in thyroid volume from baseline to follow-up; thyroid volume increased in women <40 years of age and decreased in women >40 years of age. IN A MULTIVARIATE REGRESSION MODEL, HIGHER AGE AT ENTRY WAS A PREDICTOR (P0.05) FOR THYROID VOLUME DECREASE 20% DURING THE FOLLOW-UP PERIOD (WOMEN AGED 4045 YEARS: odds ratio (OR) 4.3 (95% CI, 2.2-8.2); women aged 60-65 years: 5.8 (2.9-11.6)) and individuals of higher age were also less likely to have an increase in thyroid volume (women aged 40-45 years: OR 0.2 (0.1-0.3); women aged 60-65: OR 0.3 (0.2-0.4)). Age-dependent differences in thyroid volume and enlargement had leveled out after the Danish iodization program. Thus, the previously observed increase in thyroid volume with age may have been caused by ID.


Rescue of reapproximated flexor profundus tendons in vitro following segmental irradiation.
Segments of rabbit flexor profundus tendon were transected at their zone II midpoints. Before reapproximation, proximal and/or distal segment halves received 10,000 rads of x-radiation. Four treatment groups were examined with light and electron microscopy after 2, 4, and 8 weeks in culture: group XX had proximal and distal tendon halves irradiated, group PX had only distal tendon halves irradiated, group XD had only proximal tendon halves irradiated, and group PD served as nonirradiated control tendons. After 2 weeks, the epitenons of all nonirradiated segments had proliferated to become several cell layers thick with migratory-type cells. By 4 weeks these cells in groups PX and XD crossed the repair site and invaded the opposing irradiated segments in a previously undescribed pattern. By 8 weeks, bridging and remodeling of the repair site were evident in groups PX and XD, yet not to the extent noted in the nonirradiated control group PD. No histologically evident difference in mechanism or completeness of healing was observed between groups PX and XD, and no comparable proliferation, bridging, or remodeling was observed in the completely irradiated group XX. These observations allowed for conclusions to be drawn regarding regional involvement during intrinsic tendon healing and confirmed the pluripotency of poorly differentiated epitenocytes.


Study of the enantioseparation capability of chiral dual system based on chondroitin sulfate C in CE.
It has been reported that chiral dual system is able to improve the enantioseparation of enantiomers in many cases. Currently, the dual systems involved in CE chiral separation are mostly dual CDs systems, and the polysaccharides-based chiral dual system was reported in only one paper. To the best of our knowledge, the use of chondroitin sulfate C (CSC)-based dual system for enantiomeric separation has not been reported previously. Herein, four CSC-based chiral dual systems, namely CSC/glycogen, CSC/chondroitin sulfate A (CSA), CSC/hydroxypropyl-β-CD (HP-β-CD), as well as CSC/β-CD (β-CD), were evaluated for the first time for their enantioseparation capability by CE in this paper. During the course of the work, the influences of chiral selector concentration and buffer pH values on enantioseparation in dual systems were systematically investigated. Under the optimized conditions, the dual system consisting of CSC and glycogen exhibited better separations toward nefopam, duloxetine, sulconazole, atenolol, laudanosine, and cetirizine enantiomers compared to the single CSC or glycogen system. The combination of CSC and HP-β-CD improved the separation of amlodipine and chlorphenamine enantiomers. However, no synergistic effect was observed in the CSC/CSA and CSC/β-CD systems.


Therapeutic and prognostic predictive value of the Control Volume severity grade on proximal humerus fractures due to bone fragility.
The treatment of proximal humerus fracture complicated by bone fragility is still controversial. The aim of this study is to compare the Neer classification and the Control Volume severity grade for the accuracy in the selection of the type of treatment and for prognostic evaluation. We retrospectively collected the records of all patients admitted at the Emergency Department of our Institute, from 2013 to 2020, for a closed displaced proximal humerus fracture further investigated with a CT scan before treatment decision. We selected all patients with a minimum age of 65 years. The included fractures were retrospectively classified according to Neer, and Control Volume severity grade. The included patients were evaluated with Simple Shoulder Test (SST). A statistical analysis was performed to correlate the type of treatment and the clinical results to the Neer classification and the Control Volume severity grade. Sixty-four patients (80%), were available for the telephonically interview at a mean follow up of 4 years and were included. According to the Control Volume model, we identified fracture with a low, medium and high severity grade, in 23 (36%), 13 (20%), and, 28 (44%) cases, respectively. Fifteen patients (23,5%) were conservatively treated, whether fourty-nine patients (76,5%) were operated. We find a statistical correlation between control volume severity grade and type of treatment. No Therapeutic correlation was detected for the Neer classification. A statistical correlation between the severity grade and clinical outcome could be observed only for patients with the same type of treatment. The use of Control Volume severity grade is associated with better therapeutic and prognostic informations in confront to the Neer classification.


A new perspective to satellite-based retrieval of ground-level air pollution: Simultaneous estimation of multiple pollutants based on physics-informed multi-task learning.
Remote sensing of air pollution is essential for air quality management and health risk assessment. Many machine-learning-based retrieval models have been established for estimating various kinds of air pollutants. These methods mainly aimed to estimate a single pollutant (single-pollutant approach). However, different air pollutants interact with each other and are highly correlated. Building a unified model and conducting a joint retrieval of multiple pollutant can make a better use of these connections and improve the model efficiency. This study proposed a physics-informed multi-task deep neural network (phyMTDNN) for the joint retrieval of six main air pollutants, i.e., PM2.5, PM10, SO2, NO2, CO, and O3. The relationships among these pollutants were used to design the physics-informed network structure and loss function. Top-of-atmosphere reflectance which can generate retrieval results at ultrahigh resolution was used as model input. Experiments for mainland China in 2019 showed that the proposed model successfully achieved simultaneous estimation of six air pollutants, with the cross-validated R2 for the six pollutants varying from 0.72 to 0.90. The contrast experiments proved that physics-informed network structure contributed to the most of the model performance improvement. Compared to the single-pollutant approach, phyMTDNN ameliorated the model accuracy on traces gases retrieval. Furthermore, the modeling efficiency was largely improved in that a lot of repetitive work was avoided and modeling method was optimized. The proposed new multiple-pollutant retrieval frame can be applied to various fields for multi-variate retrieval or estimation.


Isolation of fungi from onychomycosis-suspected nails by two methods: clipping and drilling.
We examined 101 nails clinically suspected of onychomycosis by taking specimens with two different techniques: clipping and drilling. We then compared the mycological results of these two techniques. The microscopic results were similar, but culture was more successful with the clipping technique. Twenty-seven per cent of specimens obtained by clipping were culture positive for dermatophytes compared with 20% obtained by drilling and a combined positivity rate of 31%.


Factors Associated with Depression in Obsessive-Compulsive Disorder: A Cross-Sectional Study.
Major depressive disorder (MDD) is the most frequent comorbid psychiatric condition associated with obsessive-compulsive disorder (OCD). This study aimed to evaluate the prevalence of current depression in OCD, differences in socio-demographic and clinical characteristics, and obsessive-compulsive symptoms between OCD patients with and without depression. Additionally, factors associated with comorbid depression were investigated in our study. In total, 140 OCD patients, of which 63 were OCD patients with MDD (OCD+MDD, n=63) and 77 were OCD patients without depression (OCD-MDD, n=77) were included in the study. All patients were diagnosed with OCD using the Structured Clinical Interview for DSM-IV. The Yale-Brown Obsessive-Compulsive Scale, Beck Anxiety Scale, and Beck Depression Scale were administered to all patients. After the socio-demographic and clinical variables and scales were accomplished, the OCD patients divided into two groups as OCD with or without depression and we compared their mean scores of the variables and scales. Univariate analyses were followed by logistic regression. There were no significant differences in age, gender, marital status, period without treatment, profession, medical and family history, and social support between the two groups. Anxiety, depression, and obsession and compulsion scores were significantly higher in the OCD+MDD group. The avoidance, insight, instability, and retardation scores of the OCD+MDD group were also significantly higher than those of the OCD-MDD group. Our study suggests that many factors are strongly associated with depression in OCD. Positive correlations between poor insight, severity of obsession and compulsion, and stressful life events during the last six months increased the risk of depression in OCD. Our study suggests that high level of avoidance, instability and retardation, history of suicidal attempt, and delayed treatment are other notable factors associated with the development of depression in OCD.


Prevalence, male germ-line origin and new patterns of inversions in haemophilia A.
Following the discovery of the FVIII gene inversion by Lakich et al. [1] and Naylor et al. [2], we have investigated this mutation in 108 French and Algerian severe haemophilia A patients. We have found that only 29 severe haemophiliacs (27%) exhibited the rearrangement whereas Lakich et al. [1] and Naylor et al. [2] respectively estimated the inversion frequency at 47% and 42% in severe haemophiliacs. The reason for this discrepancy is not accounted for. In this study, we observed two novel patterns of inversions as yet unreported. We did not find any correlation between the presence of the inversion and a particular RLFP haplotype, or ethnic origin, or the absence of a FVIII inhibitor. Among the cases with the inversion, the proportion of sporadic and transmitted cases was roughly equivalent and we also confirm that the inversion occurs preferentially in the male germ-line.


The use of external change agents to promote quality improvement and organizational change in healthcare organizations: a systematic review.
External change agents can play an essential role in healthcare organizational change efforts. This systematic review examines the role that external change agents have played within the context of multifaceted interventions designed to promote organizational change in healthcare-specifically, in primary care settings. We searched PubMed, CINAHL, Cochrane, Web of Science, and Academic Search Premier Databases in July 2016 for randomized trials published (in English) between January 1, 2005 and June 30, 2016 in which external agents were part of multifaceted organizational change strategies. The review was conducted according to PRISMA guidelines. A total of 477 abstracts were identified and screened by 2 authors. Full text articles of 113 studies were reviewed. Twenty-one of these studies were selected for inclusion. Academic detailing (AD) is the most prevalently used organizational change strategy employed as part of multi-component implementation strategies. Out of 21 studies, nearly all studies integrate some form of audit and feedback into their interventions. Eleven studies that included practice facilitation into their intervention reported significant effects in one or more primary outcomes. Our results demonstrate that practice facilitation with regular, tailored follow up is a powerful component of a successful organizational change strategy. Academic detailing alone or combined with audit and feedback alone is ineffective without intensive follow up. Provision of educational materials and use of audit and feedback are often integral components of multifaceted implementation strategies. However, we didn't find examples where those relatively limited strategies were effective as standalone interventions. System-level support through technology (such as automated reminders or alerts) is potentially helpful, but must be carefully tailored to clinic needs.


The Charlson comorbidity index as a predictor of outcomes in liver transplantation: single-center experience.
Several comorbidity indices, such as the Child-Turcotte-Pugh (CTP) score and the Model for End-Stage Liver Disease (MELD) score, have been used to optimize available organ resources and adjust priorities in diagnosis and allocation of grafts for patients who are candidates for liver transplantation. There have also been various attempts to create instruments to accurately predict outcomes after liver transplantation, but none has proved to be truly applicable, with the exception of the Charlson comorbidity index (CCI). We retrospectively reviewed data of 221 liver recipients, including living-related liver transplantation and multiple organ transplantation performed between January 2006 and September 2009. Survival analysis revealed a significant association of the CCI with decreased posttransplantation patient survival (P = .003). Furthermore, Kaplan-Meier plots and log-rank test showed a significant association between graft survival and the score (P = .039). Our data suggest that the CCI is a simple tool for the evaluation of comorbidity and that increased preoperative patient comorbidity increases the risk of graft loss and patient death after liver transplantation. The CCI should be considered an important tool for improving patient care because of its potential applications for patient management.


GABPalpha regulates Oct-3/4 expression in mouse embryonic stem cells.
Embryonic stem (ES) cells are pluripotent cells derived from the inner cell mass of blastocysts, and transcription factors Oct-3/4, Nanog, Sox2, and STAT3, are essential for their self-renewal. In this study, we searched for molecules downstream of STAT3 in ES cells. Using DNA chip analysis, we obtained GA-repeat binding protein (GABP) alpha. Expression of GABPalpha was restricted to undifferentiated ES cells and controlled by STAT3. We found that the expression level of Oct-3/4 is reduced by knockdown of GABPalpha. On the other hand, GABPalpha-overexpressing ES cells maintained the expression level of Oct-3/4 even in the absence of LIF. Moreover, the induction of Oct-3/4 repressors Cdx-2, Coup-tf1, and GCNF was stimulated by GABPalpha knockdown. These data suggest that GABPalpha upregulates the expression of Oct-3/4 via downregulation of Oct-3/4 repressors.


Management of Chest Drains: A National Survey on Surgeons-in-training Experience and Practice.
Chest tube insertion is a simple and sometimes life-saving procedure performed mainly by surgical residents. However with inadequate knowledge and poor expertise, complications may be life threatening. We aimed to determine the level of experience and expertise of resident surgeons in performing tube thoracostomy. Four tertiary institutions were selected by simple random sampling. A structured questionnaire was administered to 90 residents after obtaining consent. The majority of respondents were between 31 and 35 years. About 10% of respondents have not observed or performed tube thoracostomy while 77.8% of respondents performed tube thoracostomy for the first time during residency training. The mean score was 6.2 ± 2.2 and 59.3% of respondents exhibited good experience and practice. Rotation through cardiothoracic surgery had an effect on the score (P = 0.034). About 80.2% always obtained consent while 50.6% always used the blunt technique of insertion. About 61.7% of respondents routinely inserted a chest drain in the Triangle of safety. Only 27.2% of respondents utilized different sizes of chest tubes for different pathologies. Most respondents removed chest drains when the output is <50 mL. Twenty-six respondents (32.1%) always monitored air leak before removal of tubes in cases of pneumothorax. Superficial surgical site infection, tube dislodgement, and tube blockage were the most common complications. Many of the surgical resident lack adequate expertise in this lifesaving procedure and they lose the opportunity to learn it as interns. There is a need to stress the need to acquire this skill early, to further educate and evaluate them to avoid complications.


Screening blood test identifies subclinical beryllium disease.
We evaluated the beryllium-specific lymphocyte transformation test as a workplace screening tool for early beryllium disease. Fifty-one of 58 workers with current beryllium exposure completed questionnaires and gave blood specimens for the lymphocyte transformation test. Six workers (11.8%) had elevated test results ranging from 5.7-fold to 16.7-fold stimulation. Of five who underwent clinical evaluation, four had beryllium disease, demonstrated by granulomata on transbronchial lung biopsy and elevated lymphocyte transformation tests by bronchoalveolar lavage cells (ranging from 18.6-fold to 44.3-fold stimulation). Our data show that (1) minimally symptomatic cases of beryllium disease can be identified by this peripheral blood test, (2) not all individuals with a positive peripheral blood lymphocyte transformation test have beryllium disease at the time of their initial evaluation, and (3) lymphocyte transformation test reproducibility is good, justifying further evaluation of this test for screening. We conclude that the peripheral blood lymphocyte transformation test may prove useful in preventing clinical chronic beryllium disease by early diagnosis in a subclinical phase.


Evaluating and improving cDNA sequence quality with cQC.
Errors are prevalent in cDNA sequences but the extent to which sequence collections differ in frequencies and types of errors has not been investigated systematically. cDNA quality control, or cQC, was developed to evaluate the quality of cDNA sequence collections and to revise those sequences that differ from a higher quality genomic sequence. After removing rRNA, vector, bacterial insertion sequence and chimeric cDNA contaminants, small-scale nucleotide discrepancies were found in 51% of cDNA sequences from one Arabidopsis cDNA collection, 89% from a second Arabidopsis collection and 75% from a rice collection. These errors created premature termination codons in 4 and 42% of cDNA sequences in the respective Arabidopsis collections and in 7% of the rice cDNA sequences.


Myxoid liposarcoma involving the liver, subcutaneous tissue, and epidural space in a polycystic disease patient.
We present a case of a myxoid liposarcoma involving the liver, subcutaneous tissue, and epidural space in a polycystic disease patient with minimally increased F-18 FDG activity and review the image findings of myxoid liposarcoma.


A comparative Langmuir-Blodgett study on a set of covalently linked porphyrin-based amphiphiles: a detailed atomic force microscopic study.
A set of covalently linked phenyl-amidophenyl-substituted porphyrin amphiphiles with n-C15H31 tails have been synthesized and completely characterized. These amphiphiles form good Langmuir-Blodgett (LB) films at the air/water interface. Mean molecular areas for the series were measured from the isotherms and found to increase as the number of aliphatic chains increased from one to four. No influence of the subphase pH was observed on the isotherms. LB films can be transferred successfully onto different solid surfaces. The LB films were characterized using tapping mode atomic force microscopy (AFM). Bis-, tris-, and tetra-substituted porphyrins were found to be fairly good film-forming amphiphiles, whereas irregular aggregates were seen in the case of the monosubstituted porphyrin amphiphile. Multilayers were also formed with tetra-substituted amphiphiles on mica. Detailed AFM studies of tetra-substituted amphiphiles have been carried out to investigate the effect of preparation procedure and solid substrates on film formation and transfer. The absorption and fluorescence spectra for the amphiphiles in solution and LB films deposited onto mica and glass were recorded, which demonstrated the successful transfer of LB films onto the substrates and provided more information about the arrangement of porphyrin molecules within the LB films. For comparison, self-assembled monolayers (SAMs) and the cast thin films of the amphiphiles were prepared and characterized.


Dermatologic changes after systemic cancer therapy.
Dermatologic changes associated with systemic cancer therapy are common. These changes can be conveniently grouped into three clinical categories: 1) cytotoxic effects; 2) pigment alterations; and 3) rashes and eruptions. The clinician should be alert to these manifestations so that needless work-up is avoided..


Synergistic effect of alcohol drinking and smoking on in vivo acetaldehyde concentration in saliva.
Alcohol drinking and smoking are independent risk factors for upper digestive tract cancers. Furthermore, their combined use interacts in a multiplicative way on cancer risk. There is convincing evidence that acetaldehyde, the first metabolite of ethanol and a constituent of tobacco smoke, is a local carcinogen in humans. Therefore, we examined the combined effect of alcohol drinking and tobacco smoking on in vivo acetaldehyde concentration in saliva. Seven smokers and 6 nonsmokers participated in the study. First, to measure the effect of alcohol on salivary acetaldehyde, all volunteers ingested 0.8 g/kg body weight of ethanol and saliva samples were collected every 20 min for 160 min thereafter. After a 3-day washout period, smokers ingested again the same amount of ethanol and smoked one cigarette every 20 min and saliva samples were collected at 10 min intervals for 160 min. Acetaldehyde and ethanol concentrations were analyzed by headspace gas chromatograph. Firstly, smokers without concomitant smoking during ethanol challenge had 2 times higher in vivo salivary acetaldehyde concentrations than nonsmokers after ethanol ingestion (AUC 114.8 +/- 11.5 vs. 54.2 +/- 8.7 microM x hr, respectively; p = 0.002). Secondly, smokers with active smoking during ethanol challenge had 7 times higher in vivo salivary acetaldehyde levels than nonsmokers (AUC 369.5 +/- 12.2 vs. 54.2 +/- 8.7 microM x hr, respectively; p < 0.001). We conclude that this markedly increased exposure of upper digestive tract mucosa to carcinogenic salivary acetaldehyde of smoking and drinking subjects may explain the synergistic and multiplicative risk effect of alcohol drinking and tobacco smoking on upper gastrointestinal tract carcinogenesis.


The Unique Role of the Pediatric Clinical Research Nurse in Anesthesia: An Interdisciplinary Collaboration.
This article describes the distinctive function of the pediatric clinical research nurse (CRN) in the anesthesia setting. The pediatric CRN in anesthesia acts as a liaison between families and the research team and is the major nexus between the principal investigator or anesthesiologist on a study, and the collaborating surgeons from many different departments. This is unique because the CRNs collaborate with physicians in specialties that can include plastics, urology, neurosurgery, orthopaedics, otolaryngology, cardiology, critical care, and many other departments. The profession requires a breath of knowledge ranging from clinical understanding of diseases, surgical procedures, and recovery to cognitive and developmental stages, to expertise in the research protocol process. Our objective was to describe these specialized activities of the pediatric anesthesia CRN, with focus on care coordination, communication, and continuity of care. Defining this role will enhance the quality of clinical research conducted by the CRN in anesthesia and may influence the development of novel medical treatments.


Expression of p53, transforming growth factor alpha, epidermal growth factor receptor, and c-erbB-2 in endometrial carcinoma and correlation with survival and known predictors of survival.
Abnormal expression of p53, transforming growth factor alpha (TGF alpha), epidermal growth factor receptor (EGFR), and c-erbB-2 occurs in a variety of cancers and in some cases is associated with poor prognosis. Immunoperoxidase staining using these markers in formalin-fixed, paraffin-embedded endometrial carcinoma tissue was performed to determine whether immunoreactivity correlates with survival and known prognostic variables. Cases included 84 endometrioid adenocarcinomas, five adenoacanthomas, 12 adenosquamous carcinomas, 11 serous carcinomas, 15 clear cell carcinomas, and one carcinosarcoma for a total of 128 cases. Frequencies of immunoreactivity were as follows: p53, 37 of 128 (29%); TGF alpha, strong (2+) 23 of 128 (18%) and intermediate (1+) 26 of 128 (20%); EGFR, strong (3+) 21 of 128 (16%) and intermediate (2+ or 1+) 83 of 128 (65%); and c-erbB-2, strong (2+) four of 128 (2%) and intermediate (1+) three of 128 (1%). p53 and TGF alpha staining showed statistically significant correlations with decreased length of survival (P < .0017 and P < .0013, respectively, generalized Savage [Mantel Cox]). p53 immunoreactivity correlated with tumor types, grade, and stage. Transforming growth factor alpha staining correlated with increased depth of invasion and presence of vascular invasion. Epidermal growth factor receptor staining did not correlate with length of survival or known prognostic variables. c-erbB-2 staining correlated with tumor type. In the multivariate analysis p53 and TGF alpha staining were not independent predictors of survival when other variables were taken into account, including grade, stage, tumor type, presence of vascular invasion, and depth of invasion. Grade and stage were the only independent predictors of survival when used in combination in a Cox proportional hazards model.


Genetic analysis of low lambda 1 chain production in mice.
Several commonly used strains of laboratory mice from Charles River Laboratories were found to produce extremely low or undetectable levels of serum immunoglobulins bearing lambda 1 light chain (lambda 1 Ig). Individual CF-1, CD-1, and CFW random-bred mice were tested for serum lambda 1 levels, lambda 1-specific anti-NP responses, and genomic polymorphisms at the lambda 1 locus. In all cases, a complete correlation among these parameters was observed. The results indicated that nearly all CFW, greater than 70% of CD-1 but none of the CF-1 mice produced low levels of lambda 1 light chain. The low lambda 1 Ig production is due to a genetic defect either similar or identical to that observed in SJL mice. The data suggest that the lambda 1 locus of CD-1, CFW, and SJL mice are derived from a common ancestor. We also surveyed lambda 1 Ig production in a series of wild mice. Mice producing low lambda 1 Ig were frequently observed. The wild mice with low lambda 1 Ig levels were captured in diverse geographic areas, including Europe, Middle East, Asia, and South America. Preliminary study suggests that the defect in the wild mice is different from that of SJL, CD-1, or CFW mice and implies that other mechanisms regulate lambda 1 Ig production in wild mice.


Continuum-Scale Modeling of Liquid Redistribution in a Stack of Thin Hydrophilic Fibrous Layers.
Macroscale three-dimensional modeling of fluid flow in a thin porous layer under unsaturated conditions is a challenging task. One major issue is that such layers do not satisfy the representative elementary volume length-scale requirement. Recently, a new approach, called reduced continua model (RCM), has been developed to describe multiphase fluid flow in a stack of thin porous layers. In that approach, flow equations are formulated in terms of thickness-averaged variables and properties. In this work, we have performed a set of experiments, where a wet 260 - μ m -thin porous layer was placed on top of a dry layer of the same material. We measured the change of average saturation with time using a single-sided low-field nuclear magnetic resonance device known as NMR-MOUSE. We have employed both RCM and the traditional Richards equation-based models to simulate our experimental results. We found that the traditional unsaturated flow model cannot simulate experimental results satisfactorily. Very close agreement was obtained by including the dynamic capillary term as postulated by Hassanizadeh and Gray in the traditional equations. The reduced continua model was found to be in good agreement with the experimental result without adding dynamic capillarity term. Moreover, the computational effort needed for RCM simulations was one order of magnitude less than that of traditional models.


Polypoid arteriovenous malformation presenting with jejunojejunal intussusceptions in an adult.
Jejunal polypoid arteriovenous malformations (AVMs) and jejunojejunal intussusceptions are both rare. Here, we present the case of a 61-year-old woman who suffered intermittent episodes of abdominal pain over the course of 13 years. A computed tomography scan of her abdomen and pelvis revealed a distal jejunojejunal intussusception. A suspected low density mass was observed at the tip of the intussusception. Treatment comprised laparoscopic small bowel resection with end-to-end jejunostomy. The final diagnosis was a polypoid AVM measuring 5×3.5×3 cm. We suggest that polypoid AVM should be considered as a differential diagnosis in patients presenting with small intestinal neoplasms.


Enhancement of misonidazole cytotoxicity by iron.
The toxicity of misonidazole (MISO) to hypoxic Chinese hamster ovary (CHO) cells in serum-free medium is enhanced by Fe(III)-EDTA. Enhancement of MISO cytotoxicity by a factor of 1.6 was seen with 2 microM Fe(III)-EDTA, while 200 microM Fe(III)-EDTA results in sensitization by a factor of 2.0. Treatment of CHO cells with the iron chelator desferal resulted in protection against the hypoxic cytotoxicity in MISO (approximate protection factor of 2.5 with 100 microM desferal). Similar results were obtained with Chinese hamster V79 cells. Fe(III)-EDTA also enhanced binding of [2-14C] MISO to cellular macromolecules while desferal decreased binding of MISO to cellular macromolecules. These results suggest that iron plays an important role in the reductive metabolism of MISO and that modification of the intracellular metal ion status may be a useful approach to modulating the biological effect of nitro compounds.


Intestinal Barrier Function and the Gut Microbiome Are Differentially Affected in Mice Fed a Western-Style Diet or Drinking Water Supplemented with Fructose.
Background: The consumption of a Western-style diet (WSD) and high fructose intake are risk factors for metabolic diseases. The underlying mechanisms are largely unclear.Objective: To unravel the mechanisms by which a WSD and fructose promote metabolic disease, we investigated their effects on the gut microbiome and barrier function.Methods: Adult female C57BL/6J mice were fed a sugar- and fat-rich WSD or control diet (CD) for 12 wk and given access to tap water or fructose-supplemented water. The microbiota was analyzed with the use of 16S rRNA gene sequencing. Barrier function was studied with the use of permeability tests, and endotoxin, mucus thickness, and gene expressions were measured.Results: The WSD increased body weight gain but not endotoxin translocation compared with the CD. In contrast, high fructose intake increased endotoxin translocation 2.6- and 3.8-fold in the groups fed the CD + fructose and WSD + fructose, respectively, compared with the CD group. The WSD + fructose treatment also induced a loss of mucus thickness in the colon (-46%) and reduced defensin expression in the ileum and colon. The lactulose:mannitol ratio in the WSD + fructose mice was 1.8-fold higher than in the CD mice. Microbiota analysis revealed that fructose, but not the WSD, increased the Firmicutes:Bacteroidetes ratio by 88% for CD + fructose and 63% for WSD + fructose compared with the CD group. Bifidobacterium abundance was greater in the WSD mice than in the CD mice (63-fold) and in the WSD + fructose mice than in the CD + fructose mice (330-fold).Conclusions: The consumption of a WSD or high fructose intake differentially affects gut permeability and the microbiome. Whether these differences are related to the distinct clinical outcomes, whereby the WSD primarily promotes weight gain and high fructose intake causes barrier dysfunction, needs to be investigated in future studies.


Nonbacterial Thrombotic Endocarditis With Embolic Phenomena Diagnosed by Transesophageal Echocardiogram.
Nonbacterial thrombotic endocarditis (NBTE) is a valvular disorder commonly associated with malignancy and connective tissue diseases. While the disorder is often discovered during autopsy, it is sometimes diagnosed in patients who present with systemic embolization. Here, we discuss the case of a 52-year-old female, with connective tissue disease and malignancy, who presented with symptoms of systemic embolization and was diagnosed with NBTE by transesophageal echocardiogram (TEE). This case highlights the utility of TEE in diagnosing NBTE and its influence in guiding the subsequent management of patients.


N-cadherin acts upstream of VE-cadherin in controlling vascular morphogenesis.
Endothelial cells express two classic cadherins, VE-cadherin and N-cadherin. The importance of VE-cadherin in vascular development is well known; however, the function of N-cadherin in endothelial cells remains poorly understood. Contrary to previous studies, we found that N-cadherin localizes to endothelial cell-cell junctions in addition to its well-known diffusive membrane expression. To investigate the role of N-cadherin in vascular development, N-cadherin was specifically deleted from endothelial cells in mice. Loss of N-cadherin in endothelial cells results in embryonic lethality at mid-gestation due to severe vascular defects. Intriguingly, loss of N-cadherin caused a significant decrease in VE-cadherin and its cytoplasmic binding partner, p120ctn. The down-regulation of both VE-cadherin and p120ctn was confirmed in cultured endothelial cells using small interfering RNA to knockdown N-cadherin. We also show that N-cadherin is important for endothelial cell proliferation and motility. These findings provide a novel paradigm by which N-cadherin regulates angiogenesis, in part, by controlling VE-cadherin expression at the cell membrane.


An assessment of the concentrations of particulate polycyclic aromatic hydrocarbons (PAHs) in the aftermath of a chemical store fire incident.
PM10 airborne particles and soot deposit collected after a fire incident at a chemical store were analyzed in order to determine the concentrations of polycyclic aromatic hydrocarbons (PAHs). The samples were extracted with 1:1 hexane-dichloromethane by ultrasonic agitation. The extracts were then subjected to gas chromatography-mass spectrometric (GC-MS) analysis. The total PAHs concentrations in airborne particles and soot deposit were found to be 3.27 +/- 1.55 ng/m3 and 12.81 +/- 24.37 microg/g, respectively. Based on the molecular distributions of PAHs and the interpretation of their diagnostic ratios such as PHEN/(PHEN + ANTH), FLT/(FLT + PYR) and BeP/(BeP + BaP), PAHs in both airborne particles and soot deposit may be inferred to be from the same source. The difference in the value of IP/(IP + BgP) for these samples indicated that benzo[g, h, i] perylene and coronene tend to be attached to finer particles and reside in the air for longer periods. Comparison between the molecular distributions of PAHs and their diagnostic ratios observed in the current study with those reported for urban atmospheric and roadside soil particles revealed that they are of different sources.


Assessment of the protective potential of Premna tomentosa (L. Verbenaceae) extract on lipid profile and lipid-metabolizing enzymes in acetaminophen-intoxicated rats.
The liver is often damaged by environmental toxins, poor eating habits, alcohol and over-the-counter drug use that damage and weaken the liver, leading to important public health problems such as hepatitis, cirrhosis, and alcoholic liver diseases. It is cardinal to treat liver disorders, because it affects the biochemistry of the cell directly. Damage to the liver can be prevented by including a balanced diet that includes nutrients and herbs that support a healthy liver. Premna tomentosa (PT) is one such herbal drug used widely in India for the treatment of liver disorders, and we have already reported the hepatoprotective potential and antioxidant property of methanolic extract of PT leaves. Because injury to the liver can promote a variety of reactions with consequent effect on lipids, the present study was designed to elucidate the hypolipidemic effect of PT extract in acetaminophen (AA)-induced hepatotoxicity in rats. Animals were pretreated with PT extract (750 mg/kg, orally) for 15 days and then induced with hepatotoxicity by AA (640 mg/kg, intraperitoneally). PT extract pretreatment significantly inhibited induced alterations in the levels of cholesterol, triglycerides, free fatty acids, phospholipids, serum lipoproteins, and lipid-metabolizing enzymes. The results indicate that PT extract improves lipid metabolism and has the potential for use in hepatic disorders.


A noninvasive technique for monitoring lung vascular permeability in man.
Increased microvascular permeability resulting in increased plasma protein extravasation is the hallmark of acute inflammatory oedema and hence radiolabelled proteins can be used to monitor this process. The adult respiratory distress syndrome (ARDS) is characterized by acute inflammatory oedema and thus provides an ideal model for studying this type of oedema in the human lung. A noninvasive technique applicable to the intensive care unit has been developed for monitoring the pulmonary accumulation of the plasma protein transferrin. Transferrin was radiolabelled in vivo with indium-113m and its accumulation was monitored using a portable probe radiation detector. After correcting for changes in intrathoracic blood distribution, by simultaneously monitoring the accumulation of technetium-99m-labelled red blood cells, an index of plasma protein accumulation was calculated. In all patients with established ARDS (n = 10) the index values were greater than 1.0 X 10(-3) min-1 and these were clearly separate from the values of less than 0.5 X 10(-3) min-1 in all healthy volunteers (n = 5; P less than 0.001). The technique can clearly detect raised plasma protein accumulation indices in the lungs of patients with established inflammatory oedema of ARDS and hence may provide a pharmacological tool for the rapid evaluation in these conditions of the effects of drugs (like corticosteroids) which are known to modulate inflammatory oedema.


Ecological impacts of atmospheric CO2 enrichment on terrestrial ecosystems.
Global change has many facets, of which land use and the change of atmospheric chemistry are unquestioned primary agents, which induce a suite of secondary effects, including climatic changes. The largest single contribution to the compositional change of the atmosphere, CO(2) enrichment, has (besides its influence on climate) immediate and direct effects on plants. Quantitatively, CO(2) is the plant 'food' number one, and the rate of photosynthetic CO(2) uptake by leaves is not yet CO(2)-saturated. This abrupt change of the biosphere's diet does and will affect all aspects of life, including our food. However, the plant and ecosystem responses are more subtle than had been assumed from the results of responses of isolated, well-fertilized and well-watered plants in greenhouses during the early days of CO(2)-enrichment research. In this article, I discuss potential responses of complex natural grassland and diverse forests, and address three key themes: CO(2) and nutrients; CO(2) and water; CO(2) and plant-animal interactions. Examples from a suite of climatic regions emphasize that the most important ecosystem level responses to elevated CO(2) will be introduced by differential responses of species. Atmospheric CO(2) enrichment is a biodiversity issue. Classical physiological baseline responses of leaves to elevated CO(2) can be overrun by biodiversity effects to such an extent that some of the traditional predictions may even become reversed. For instance, biodiversity effects may cause humid tropical forests (those which avoid destruction) to become more dynamic and store less, rather than more, carbon as CO(2) enrichment continues. The abundance of certain life forms and species and their lifespans exert major controls over the half-life of carbon stored in forest biomass, and there is evidence that elevated CO(2) can affect these controls and most likely does so already. Also, long-term hydrological consequences of atmospheric CO(2) enrichment will be driven by biodiversity effects, given that some, but not all, species reduce their rate of water loss when exposed to a CO(2)-rich atmosphere. Such insights call for much more realistic experimental conditions and larger-scale test units, which permit biotic interactions across taxa and trophic levels to occur while simulating our CO(2) future. The evidence currently available suggests that ecosystem processes reflect the composition of their biological inventory and this will be affected by a shift in carbon supply.


Nuclear microRNA-466c regulates Vegfa expression in response to hypoxia.
MicroRNAs are well characterized in their role in silencing gene expression by targeting 3´-UTR of mRNAs in cytoplasm. However, recent studies have shown that miRNAs have a role in the regulation of genes in the nucleus, where they are abundantly located. We show here that in mouse endothelial cell line (C166), nuclear microRNA miR-466c participates in the regulation of vascular endothelial growth factor a (Vegfa) gene expression in hypoxia. Upregulation of Vegfa expression in response to hypoxia was significantly compromised after removal of miR-466c with CRISPR-Cas9 genomic deletion. We identified a promoter-associated long non-coding RNA on mouse Vegfa promoter and show that miR-466c directly binds to this transcript to modulate Vegfa expression. Collectively, these observations suggest that miR-466c regulates Vegfa gene transcription in the nucleus by targeting the promoter, and expands on our understanding of the role of miRNAs well beyond their canonical role.


Managing Ammonia Emissions From Screwworm Larval Rearing Media.
Mass production, sterilization, and release of screwworms (Cochliomyia hominivorax (Coquerel)) that were competitive in the field significantly contributed to the successful application of the sterile insect technique for eradication of screwworms from continental North America. Metabolic byproducts resulting from protein-rich diets required for larval screwworms lead to ammonia liberation, sometimes at high levels, within the mass rearing facility. Until recently a sodium polyacrylate gel bulking agent was used for the larval media and adsorbed much of the ammonia. A need to replace the gel with an environmentally "friendly" bulking agent, while not increasing ammonia levels in the rearing facility, led to a series of experiments with the objective of developing procedures to reduce ammonia emissions from the larval media bulked with cellulose fiber. Additives of ammonia-converting bacteria, potassium permanganate, and Yucca schidigera Roezl ex Otrgies powder extract, previously reported to reduce ammonia levels in organic environments, were evaluated. Ammonia-converting bacteria did not have a positive effect. Addition of Y. schidigera powder extract (∼1% of total volume), potassium permanganate (∼250 ppm), and a combination of these two additives (at these same concentrations) kept ammonia at equivalent levels as when larval media was bulked with gel. Potassium permanganate also had sufficient antimicrobial properties that the use of formaldehyde in the diet was not necessary. Further testing is needed, at a mass rearing level, before full implementation into the screwworm eradication program.


Genetics of neuroendocrine factors in rheumatoid arthritis.
Inadequate production of cortisol related to inflammation and decrease in adrenal androgen production are hallmarks of hypothalamic-pituitary-adrenal (HPA)-related endocrine findings in rheumatoid arthritis (RA). In particular, lower dehydroepiandrosterone sulfate (DHEAS) levels were consistently found in a subset of premenopausal RA females. Recently, several new gene variants have been identified in association with serum DHEAS concentrations, such as in SULT2A1 and HHEX genes. These DHEAS-related genes and other variants involved in HPA regulation may play a role in the adrenal androgen deficiency in RA. The aim of our study was to review involvement of genetic mechanisms of HPA regulation, with focus on adrenal androgens, in the context of RA pathophysiology. Although, effects of the DHEAS-related gene variants appear to be relatively small compared to other well-known factors such as age, complex interactions between DHEAS-associated genotypes and adrenal androgen hypofunction phenotype may exist in RA. Further studies analyzing specific neuroendocrine phenotype/genotype in RA are needed.


Asp129 of low molecular weight protein tyrosine phosphatase is involved in leaving group protonation.
Site-directed mutagenesis was used to explore the functions of a number of acidic residues of bovine low molecular weight protein tyrosine phosphatase. Residues Asp-129, Asp-56, and Asp-92 were mutated to Ala or Asn. The mutant enzymes D56A, D56N, and D92A showed no significant changes in Vmax values, although they did exhibit significantly altered Km values. In contrast, the D129A mutant enzyme exhibited a greater than 2000-fold reduction in Vmax, using p-nitrophenyl phosphate as a substrate. The Vmax values of D129A also exhibited a leaving group dependence, an altered solvent isotope effect of VmaxH/VmaxD of 0.78, and a lack of dependence on the presence of alternative phosphate acceptor alcohols, all properties that distinguish this mutant from wild type enzyme. The differences are due to a change of the rate-limiting step of the catalytic reaction. Asp-129 is concluded to be the proton donor to the leaving group in the phosphorylation step, and its mutation to alanine results in a reduced Vmax value and a change in the rate-limiting step of the catalysis from dephosphorylation to phosphorylation. Mechanistic considerations suggest that other phosphotyrosyl phosphatases having cysteine at the active site may be expected to have a similar requirement for a proton donor.


Bone Marrow Mesenchymal Stem-Cell Transplantation Promotes Functional Improvement Associated with CNTF-STAT3 Activation after Hemi-Sectioned Spinal Cord Injury in Tree Shrews.
Hemi-sectioned spinal cord injury (hSCI) can lead to spastic paralysis on the injured side, as well as flaccid paralysis on the contralateral side, which can negatively affect a patient's daily life. Stem-cell therapy may offer an effective treatment option for individuals with hSCI. To examine the role of bone marrow mesenchymal stem cells (BMSCs) transplantation on hSCI and explore related mechanisms in the tree shrews, here, we created a model of hSCI by inducing injury at the tenth thoracic vertebra (T10). Hoechst 33342-labeled BMSCs derived from adult tree shrews were isolated, cultured, and implanted into the spinal cord around the injury site at 9 days after injury. The isolated BMSCs were able to survive, proliferate and release a variety of neurotrophic factors (NTFs) both in vitro and in vivo. At 28 days after injury, compared with the sham group, the hSCI group displayed scar formation and dramatic elevations in the mean interleukin 1 beta (IL-1β) density and cell apoptosis level, whereas the expression of signal transducer and activator of transcription 3 (STAT3) and ciliary neurotrophic factor (CNTF) mRNA was reduced. Following BMSC transplantation, motoneurons extent of shrinkage were reduced and the animals' Basso, Beattie, and Bresnahan (BBB) locomotion scale scores were significantly higher at 21 and 28 days after injury when compared with the injured group. Moreover, the hSCI-induced elevations in scar formation, IL-1β, and cell apoptosis were reduced by BMSC transplantation to levels that were close to those of the sham group. Corresponding elevations in the expression of STAT3 and CNTF mRNA were observed in the hSCI + BMSCs group, and the levels were not significantly different from those observed in the sham group. Together, our results support that grafted BMSCs can significantly improve locomotor function in tree shrews subjected to hSCI and that this improvement is associated with the upregulation of CNTF and STAT3 signaling.


Eosinophilia-myalgia syndrome and fasciitis with an active alveolitis.
This patient clearly had the EMS with eosinophilic fasciitis, apparently due to L-tryptophan. He also had an active alveolitis with a DIP-UIP-like picture. The lung findings were not similar to those reported in the Mayo series. It is perhaps most likely that his interstitial lung disease was of the cryptogenic variety and unrelated to the L-tryptophan. However, a more direct association cannot be ruled out until more cases with similar findings are thoroughly evaluated. We suggest that special consideration of pertinent studies for interstitial lung disease is merited in all patients with suspected EMS. These might include diffusing capacity, gallium scans of lungs, broncho-alveolar lavage and possibly lung biopsy.


Correlates and predictors of alcohol consumption and negative consequences of alcohol use among Latino migrant farmworkers in Nebraska.
Alcohol is a significant issue among the Latino farmworker population. This study used cross-sectional data from the Nebraska Migrant Farmworker Health Study, 2016 (N = 241) to (1) describe drinking behavior, (2) evaluate associations between alcohol consumption and negative consequences from alcohol use and various social and demographic variables, and (3) assess contextual and interpersonal predictors of alcohol consumption and negative consequences from alcohol use. Descriptive, bivariate statistics and hierarchical multiple regression were used. Results indicated that over 30% of participants had engaged in heavy drinking in the last year. Alcohol consumption was significantly positively associated with negative consequences of alcohol use and significantly negatively associated with work safety climate and age. Negative consequences from alcohol use was significantly negatively associated with work safety climate. Significant predictors of alcohol consumption included work safety climate and age. Being married or in a relationship, alcohol consumption, and work safety climate were significant predictors of negative consequences from alcohol use. This study highlights the potential positive spillover effect of work safety climate on worker drinking behaviors. Implications and recommendations for agricultural employers, farmworker health advocates, and social service agencies are discussed. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Orbital decompression: cadaver study.
Patients with Graves' ophthalmopathy may need surgical treatment to alleviate ophthalmologic complications. The degree of reduction in proptosis following surgical intervention remains difficult to predict. To elaborate a human model using cadaver orbits to study surgical management of Graves' ophthalmopathy. To evaluate quantitatively the contribution of each orbital wall decompression and their combinations in reduction in proptosis. To improve the ability to predict the degree of proptosis reduction according to the wall(s) chosen for decompression. Artificial exophthalmos was created in 12 cadavers' orbits by injecting a polysaccharide gel in the peribulbar and retrobulbar tissues. Proptosis reduction was measured following successive orbital decompression. Decompression of one wall produced a nonstatistical significant reduction in proptosis. The combination of the medial and lateral walls significantly reduced the proptosis by a mean of 4.2 mm. Three-wall decompression gave a mean significant reduction of 6.6 mm, and when combined with the advancement of the lateral wall, it reduced proptosis by 12.5 mm. We created an experimental model for research and didactic purposes for surgical mangement of Graves' ophthalmopathy. With this model, to obtain 5 mm or more of proptosis reduction, three-wall decompression is required. Advancement of the lateral wall achieved a further reduction in proptosis. For a proptosis reduction of less than 5 mm, decompression of the medial and lateral walls is appropriate.


Managing hemolyzed samples in clinical laboratories.
Hemolysis is conventionally defined as membrane disruption of red blood cells and other blood cells that is accompanied by subsequent release of intracellular components into the serum or plasma. It accounts for over 60% of blood sample rejections in the laboratory and is the most common preanalytical error in laboratory medicine. Hemolysis can occur both in vivo and in vitro. Intravascular hemolysis (in vivo) is always associated with an underlying pathological condition or disease, and thus careful steps should always be taken by the laboratory to exclude in vivo hemolysis with confidence. In vitro hemolysis, on the other hand, is highly preventable. It may occur at all stages of the preanalytical phase (i.e. sample collection, transport, handling and storage), and may lead to clinically relevant, yet spurious, changes in patient results by interfering with laboratory measurements. Hemolysis interference is exerted through several mechanisms: (1) spectrophotometric interference, (2) release of intracellular components, (3) sample dilution and (4) chemical interference. The degree of interference observed depends on the level of hemolysis and also on the assay methodology. Recent evidence shows that preanalytical practices related to detection and management of hemolyzed samples are highly heterogeneous and need to be standardized. The Working Group for Preanalytical Phase (WG-PRE) of the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) has published many recommendations for facilitating standardization and improvement of this important preanalytical issue. Some key EFLM WG-PRE publications related to hemolysis involve: (i) a call for more transparency and some practical recommendations for improving the harmonization of the automatic assessment of serum indices and their clinical usefulness, specifically the hemolysis index (H-index), (ii) recommendations on how to manage local quality assurance of serum or plasma hemolysis/icterus/lipemia-indices (HIL-indices) and (iii) recommendations on how to detect and manage hemolyzed samples in clinical chemistry testing. In this review we provide a comprehensive overview of hemolysis, including its causes and effects on clinical laboratory assays. Furthermore, we list and discuss the most recent recommendations aimed at managing hemolyzed samples in everyday practice. Given the high prevalence of hemolyzed blood samples, the associated costs, the great heterogeneity in how hemolysis is handled across healthcare settings, countries and continents, and increasing patient cross-border mobility, standardization and quality improvement processes aimed at combatting this important preanalytical problem are clearly warranted.


Clear cell adenocarcinoma of the tunica vaginalis of the testis with an adjacent uterus-like tissue.
Testicular and paratesticular neoplasms that resemble the common epithelial type of ovarian tumor are quite rare. Paratesticular clear cell carcinoma is very uncommon in the testis, with no reported cases of a tumor arising from the tunica vaginalis in the literature to our knowledge. The present case shows that it is highly malignant and metastatic. The differential diagnosis of the tumor was made after thorough clinical, pathological and immunohistochemical investigations, from the mesothelioma of the tunica vaginalis, paratesticular serous papillary carcinoma, carcinoma of the rete testis, epididymal adenocarcioma, yolk sac tumor of the testis and metastatic carcinoma. The tumor showed Bcl-2 and Her-2/neu immunoreactivity, but was non-reactive for p53. This tumor, with a uterus-like structure as a paratesticular tumor-like mass, was composed of endometrial-type glands and stroma surrounded by bundles of smooth muscle, and is the third example of this kind of structure in English written literature. The patient, having normal external genitalia and fertility, represents the first reported case of paratesticular malignant differentiation of müllerian-type epithelium in the normal gonadal state. Müllerian-type epithelium located in the vicinity of the testis and/or endometriotic metaplasia of the mesothelium of the tunica vaginalis might be the possible origins for this uterus-like structure, and as a result, for this tumor.


Blinding was judged more difficult to achieve and maintain in nonpharmacologic than pharmacologic trials.
To compare the feasibility of blinding and the perceived risk of unblinding in trials evaluating pharmacologic (PT) and nonpharmacologic treatments (NPT) of hip or knee osteoarthritis. Two independent reviewers assessed the feasibility of blinding patients, care providers, and outcome assessors, the perceived risk of unblinding, and whether blinding was reported in 110 reports of randomized controlled trials (RCTs) evaluating PT and NPT in patients with hip or knee osteoarthritis. Blinding was considered to be possible less often in NPT trials than in PT trials for patients (42 vs. 96%; P <.001), care providers (12 vs. 96%; P <.001), and outcome assessors (34 vs. 98%; P <.001). When blinding was judged feasible, the perceived risk of unblinding was more often considered moderate or important in NPT than PT trials for patients (35 vs. 14%, P=.02) and outcome assessors (44 vs. 10%, P=.0004). When blinding was judged feasible, it was reported less often in NPT reports than in PT reports for patients (46 vs. 98%, P <.001), care providers (43 vs. 83%, P=.03), and outcome assessors (72 vs. 98%, P=.0006). Blinding appears to be more difficult to achieve and unblinding may occur more often in NPT than PT trials.


Reversible morphological and functional abnormalities of RINm5F cells cultured on polystyrene sulfonate beads.
RINm5F cells (an insulin-secreting cell line) were cultured on PSSO3Na microbeads under static conditions. The cell growth rate was either identical to that of cells grown on plastic wells or slower, depending on the initial cell concentration. With both supports, it was similarly influenced by the fetal calf serum concentration in the culture medium, and protein content per cell was identical. However, no spreading was observed when cells were cultured on microbeads. RINm5F cells cultured on plastic wells responded to arginine + theophylline and to leucine + theophylline by a significant increase in insulin secretion. By contrast, in cells cultured on PSSO3Na microbeads, the increase in this secretion was only slight or nil. All these abnormalities were reversible. Thus, when cells cultured on microbeads were detached and seeded on plastic wells, normal spreading and insulin secretion were observed. Lastly, PSSO3Na beads had an acute suppressive effect on insulin secretion by cells cultured on plastic wells. This study provides an example of cell-biomaterial interaction in which cell growth is possible, but with altered cell function.


Determining the Impact of the COVID-19 Pandemic on Availability, Use, and Readiness of Family Planning and Contraceptive Services at Selected Primary Health Care Facilities in Africa and Asia: Protocol for a Mixed Methods Study.
The COVID-19 pandemic and the associated social restrictions may have disrupted the provision of essential services, including family planning (FP) and contraceptive services. This protocol is adapted from a generic study protocol titled "Health systems analysis and evaluations of the barriers to availability and readiness of sexual and reproductive health services in COVID-19 affected areas," conducted by the World Health Organization (WHO) Department of Reproductive Health and Research. This study aims to assess the availability and use of FP and contraceptive services in primary health facilities during and after the COVID-19 pandemic; assess the risk perceptions of COVID-19 stigma, barriers to access, and quality of services from clients' and providers' perspectives in the COVID-19-affected areas; and assess the postpandemic recovery of the facilities in the provision of FP and contraceptive services. In-depth interviews will be conducted with clients-women in the reproductive age group and their male partners who visit the selected health facilities for FP and contraceptive services-and health providers (the most knowledgeable person on FP and contraceptive service provision) at the selected health facilities. Focus group discussions will be conducted with clients at the selected health facilities and in the community. The in-depth interviews and focus group discussions will help to understand clients' and health service providers' perspectives of FP and contraceptive service availability and readiness in COVID-19-affected areas. A cross-sectional health facility assessment will be conducted in all the selected health facilities to determine the health facility infrastructure's ability and readiness to provide FP and contraceptive services and to capture the trends in FP and contraceptive services available during the COVID-19 pandemic. Scientific approval for this study is obtained from the WHO Research Project Review Panel, and the WHO Ethics Review Committee has given ethical approval in the 3 countries. Using a standardized research protocol will ensure that the results from this study can be compared across regions and countries. The study was funded in March 2021. It received ethics approval from the WHO Ethics Review Committee in February 2022. We completed data collection in September 2022. We plan to complete the data analysis by March 2023. We plan to publish the study results by Summer 2023. The findings from this study will provide a better understanding of the impact of the COVID-19 pandemic on FP and contraceptive services at the facility level, which will help policy makers and health managers develop and strengthen FP policies and services in health facilities to be more responsive to community needs. DERR1-10.2196/43329.


Stroke registration in Göteborg, Sweden, 1971-75. Clinical profile and prognosis.
Strokes occurring in persons 15-65 years of age (population 300 000) have been registered since 1970 in Göteborg, Sweden. From 1971 to 1974, 640 patients were registered and followed for at least one year. Coexisting cardio-cerebrovascular diseases were more frequent in the stroke patients than in random samples of the population of Göteborg of similar ages for each sex. At three weeks the degree of neurological deficit and type of stroke were decisive for prognosis, while the presence of cardio-cerebrovascular diseases influenced fatality rates negatively at one year. Key words: stroke (cerebrovascular disorders), stroke type (cerebral infarction, cerebral hemorrhage, subarachnoid hemorrhage), clinical profile, coexisting cardiovascular diseases, fatality rates.


Flexor tendon injuries: Repair & Rehabilitation.
Flexor tendon injuries are common and occur mostly by penetrating trauma. Suspected flexor tendon injuries require a thorough clinical assessment and often are not isolated injuries. A detailed understanding of flexor tendon anatomy and spatial relationships is essential, especially when repairing multi-tendon injuries. Principles of flexor tendon repair include a strong suture construct, minimising gap formation between tendon ends, preserving tendon blood supply and providing a smooth repair interface. Moreover, adequate exposure of the zone of injury using full-thickness skin flaps and preservation of neurovascular and pulley structures is essential. In this article an overview of contemporary management strategies is presented. Today's hand surgeons and therapists can choose from a variety of treatment options when managing these important and potentially life-changing injuries.


[Construction and application of subgenomic replicon vectors of Japanese encephalitis virus].
Based on the infectious clone of JEV vaccine SA14-14-2, the subgenomic replicons pCTCJEV, pCTMJEV with large deletions in the structural region were constructed. Then they were transfected into BHK-21 cell, the RNA replication of JEV subgenome can be monitored by RT-PCR and the non-structural protein can be found expressed in the cell by IFA. To explore the possibility of using a reporter gene assay to monitor synthesis of the positive-strand and the negative-strand JEV RNA, we inserted an enhanced green fluorescence protein (EGFP) gene into the 3'-UTR of pCTCJEV, pCTMJEV under the control of the internal ribosomal entry site (IRES) of encephalomyelocarditis virus RNA. After transfection, the EGFP fluorescence could be seen under the fluorescence microscope 1 day later,and maintained for more than a week with no apparent cytopathic effect. The constructed JEV replicons would provide valuable tools to provide a possible vector for a long-lasting RNA virus expression system.


Mitochondrial DNA mutations in chemical carcinogen-induced rat bladder and human bladder cancer.
Mitochondrial (mt) DNA mutations have been described recently in different tumors, whereas similar studies focusing on bladder cancer are scarce. In an effort to understand the significance of mtDNA mutations in bladder cancer, we investigated the mtDNA alterations in both clinical human bladder cancer and in a carcinogen-induced rat bladder cancer model. Human bladder cancer tissues were obtained by radical cystectomy and transurethral resection of bladder tumors. Rat bladder tumors were induced in SD rats by treatment with N-butyl-N-(4-hydroxybutyl) nitrosamine in drinking water for 24-28 weeks. Genomic DNA was extracted from tumor specimens and microdissected normal bladder mucosae. Mitochondrial genes and D-loop region were amplified by PCR. The amplified PCR fragments were either cloned into plasmid vector or used for direct DNA sequencing. The results of DNA sequence revealed numerous point mutations in the non-coding D-loop region and different mtDNA genes in both human and rat bladder cancers. In addition, we also detected deletions of variable lengths in mononucleotide repeats in the D-loop region, ND2, ATPase 8 and COIII genes in human bladder cancer samples. Our results show that mtDNA exhibits a high rate of mutations in both human and rat bladder cancers. We also demonstrate that the repetitive sequences of mononucleotides within the mt genome are unstable and subjected to deletions. The high incidence of mtDNA mutations in bladder cancer suggests that mtDNA and mitochondria could play an important role in the process of carcinogenesis and also mtDNA could be valuable as a marker for early bladder cancer diagnosis.


Analysis of Patient Outcomes Using the MyoKinesthetic System for the Treatment of Low Back Pain: A Case Series.
The purpose of this case series was to test the feasibility of using the MyoKinesthetic (MYK) System as a treatment-based classification system and intervention for a sample of patients with low back pain. This within-subject intervention was completed in a university athletic training clinic. Nine participants (mean age: 31 years) with a primary complaint of LBP were evaluated and included. An athletic trainer performed the initial assessment, which contained the following components: patient history, palpation, range of motion testing, lower quarter neurologic screening, MYK System posture screen, orthopedic special tests, and baseline data for pain intensity, disability, and function. All participants were treated with the MYK System. The primary outcomes were pain, disability, function, active range of motion, posture, and global efficacy of treatment. The mean number of MYK treatments administered was 12.11 (SD = 6.25), and the mean number of days until discharge was 28.67 (SD = 9.38). A repeated-measures analysis of variance revealed statistically significant and clinically meaningful improvements in pain, disability, function, and posture from the initial evaluation to discharge and from the initial evaluation to a 1-month follow-up (P < .01). This study determined the feasibility of further evaluation of the MYK System as a treatment-based classification system and intervention for patients with low back pain.


Regulation of neuropeptide expression in sympathetic neurons. Paracrine and retrograde influences.
Sympathetic neurons and other peripheral neurons exhibit a great deal of plasticity in their neuropeptide phenotype in adulthood. In this review, two phenotypes have been described in detail: that of normal sympathetic neurons and that of axotomized neurons. Two factors produced by nonneuronal cells, LIF and NGF, determine which of these phenotypes is expressed. Under normal conditions, the neurons receive NGF primarily, if not exclusively, from the target tissues they innervate. Prior to surgery, the nonneuronal cells within the ganglion and nerve tract express little, if any, LIF. This milieu favors the expression of NPY and suppresses the expression of VIP, galanin, and substance P (Fig. 6). After axotomy, however, this situation is reversed. The neuronal cell bodies are deprived of target-derived NGF and are exposed to LIF both within the ganglion and at the site of the injury (Fig 6). Both the removal of NGF and the exposure to LIF inhibit NPY expression, while promoting the expression of VIP and galanin. Expression of substance P after axotomy occurs primarily, if not entirely, because of the effects of LIF, with the removal of NGF playing no obvious role in the regulation of this peptide.


Gastrointestinal complications of laparoscopic Roux-en-Y gastric bypass surgery: clinical and imaging findings.
To report the complications and imaging findings in a large group of patients who underwent Roux-en-Y gastric bypass (GBP) surgery. Four hundred sixty-three patients were evaluated for upper gastrointestinal (GI) complications following Roux-en-Y GBP surgery. Major complications were those that required surgical or radiologic intervention and minor complications were those that resolved spontaneously. The time from surgery to complication and findings from upper GI series and computed tomography (CT) of the major complications and minor leaks were reviewed. Forty-four patients had 56 major complications: 23 small-bowel obstructions (14 internal hernias and nine adhesions), 16 major leaks, 15 anastomotic strictures, and two fistulas. There were 13 minor leaks and 18 other complications. Internal hernias were late complications and had a variety of findings at upper GI series and CT. Leaks were early complications and usually originated from the gastrojejunal anastomosis; findings from upper GI series and CT demonstrated extraluminal gas, contrast material, or both. Anastomotic strictures were late complications and were diagnosed at upper GI series with rounded dilation of the pouch and delayed emptying. Upper GI complications that required intervention occurred in 9.5% of patients. CT and upper GI series can depict most major complications.


Predictive Analysis of Wettability of Al-Si Based Multiphase Alloys and Aluminum Matrix Composites by Machine Learning and Physical Modeling.
Wetting of multiphase alloys and their composites depends on multiple parameters, and these relationships are difficult to predict from first principles only. We study correlations between the composition, surface finish, and microstructure of Al-Si alloys (Si content 7-50%) and Al metal matrix composites (MMCs) with graphite (Gr), NiAl3, and SiC and the water contact angle (CA) experimentally, theoretically, and with machine learning (ML) techniques. Their surface properties were modified by mechanical abrasion, etching, and addition of alloying elements. An ML approach was developed to investigate correlations between the predictor variables (properties of the materials) and the CA. Theoretical models of wetting of rough surfaces (Wenzel, Cassie-Baxter, and their modifications) do not fully capture the CA, while ML models follow the experimental values. A full factorial design is utilized with combinations of all levels of the predictor factors (grit size, silicon percentage, droplet size, elapsed time, etching, reinforcing particles). To map the predictor variables to the response variables, 409 experimental data points were applied to train and test various supervised ML models, namely, regression, artificial neural network (ANN), chi-square automatic interaction detection (CHAID), extreme gradient boosting (XGBoost), and random forest. The correlations between the most significant factors and CA are explored through visualization techniques. The most accurately trained model shows a strong positive linear correlation (r > 0.9) between predicted and observed CA values in the test set, indicating the robustness of the model. The experimental measurements and artificial intelligence results demonstrate that CA increases following mechanically abrading the surface, etching, and adding Gr to the surface. The ML methods are promising to predict wetting properties and to provide a deeper understanding of the physical phenomena associated with the wettability of metallic alloys and their metal matrix composites.


Alteration of tryptophan-mediated regulation in Neurospora crassa by indoleglycerol phosphate.
The accumulation of imidazoleglycerol phosphate during growth of Neurospora crassa in the presence of 3-amino-1,2,4-triazole was found to cause derepression of tryptophan synthetase and to inhibit the induction of kynureninase. Accumulation of indoleglycerol phosphate in response to growth in the presence of indole acrylic acid or anthranilic acid was also accompanied by derepressed synthesis of tryptophan synthetase. Enzyme synthesis in mutants (his-7 and trp-4) unable to form these intermediates was not altered under similar conditions. The rate of formation of tryptophan synthetase and kynureninase was found to differ in the presence of tryptophan and indole.


The ArfGAP Glo3 is required for the generation of COPI vesicles.
The small GTPase Arf and coatomer (COPI) are required for the generation of retrograde transport vesicles. Arf activity is regulated by guanine exchange factors (ArfGEF) and GTPase-activating proteins (ArfGAPs). The ArfGAPs Gcs1 and Glo3 provide essential overlapping function for retrograde vesicular transport from the Golgi to the endoplasmic reticulum. We have identified Glo3 as a component of COPI vesicles. Furthermore, we find that a mutant version of the Glo3 protein exerts a negative effect on retrograde transport, even in the presence of the ArfGAP Gcs1. Finally, we present evidence supporting a role for ArfGAP protein in the generation of COPI retrograde transport vesicles.