Intraoperative intra-aortic balloon pump improves 30-day outcomes of patients undergoing extensive coronary endarterectomy.
The efficacy of intra-aortic balloon pump (IABP) has been proven in high-risk patients undergoing coronary artery bypass grafting (CABG). However, data on the timing and benefits of IABP support in diffuse coronary artery disease after CABG combined with coronary endarterectomy (CE) remain scarce. This retrospective study assessed the effect of intraoperative or postoperative IABP on 30-day outcomes of off-pump CABG+CE. From January 2012 to December 2018, 546 patients undergone off-pump CABG+CE were divided into control group (n = 437) and IABP group (n = 109). Risk factors for 30-day outcomes were evaluated. Subgroup analysis from IABP group was conducted to identify the effect of timing IABP on 30-day outcomes. CE on left anterior descending branch of coronary artery (LAD) (OR = 3.079, 95% CI 1.077-8.805, P = 0.036), CE with≥2 vessels (OR = 9.123, 95% CI 3.179-26.033, P < 0.001) and length of atherosclerotic plaque ≥3 cm (OR = 16.017, 95% CI 5.941-43.183, P < 0.001) were independent risk factors for postoperative acute myocardial infarction (AMI) and 30-day mortality. Comparing with intraoperative IABP support, postoperative IABP support (OR = 3.987, 95% CI1.194-13.317, P = 0.025) was closely associated with postoperative AMI and 30-day mortality. For patients undergone off-pump CABG and extensive CE (CE on LAD, CE ≥2 vessels and length of atherosclerotic plaque ≥3 cm), intraoperative IABP support may improve 30-day outcomes.


Powerful rare variant association testing in a copula-based joint analysis of multiple phenotypes.
In genetic association studies of rare variants, the low power of association tests is one of the main challenges. In this study, we propose a new single-marker association test called C-JAMP (Copula-based Joint Analysis of Multiple Phenotypes), which is based on a joint model of multiple phenotypes given genetic markers and other covariates. We evaluated its performance and compared its empirical type I error and power with existing univariate and multivariate single-marker and multi-marker rare-variant tests in extensive simulation studies. C-JAMP yielded unbiased genetic effect estimates and valid type I errors with an adjusted test statistic. When strongly dependent traits were jointly analyzed, C-JAMP had the highest power in all scenarios except when a high percentage of variants were causal with moderate/small effect sizes. When traits with weak or moderate dependence were analyzed, whether C-JAMP or competing approaches had higher power depended on the effect size. When C-JAMP was applied with a misspecified copula function, it still achieved high power in some of the scenarios considered. In a real-data application, we analyzed sequencing data using C-JAMP and performed the first genome-wide association studies of high-molecular-weight and medium-molecular-weight adiponectin plasma concentrations. C-JAMP identified 20 rare variants with p-values smaller than 10-5 , while all other tests resulted in the identification of fewer variants with higher p-values. In summary, the results indicate that C-JAMP is a powerful, flexible, and robust method for association studies, and we identified novel candidate markers for adiponectin. C-JAMP is implemented as an R package and freely available from https://cran.r-project.org/package=CJAMP.


Bio-processing of copper from combined smelter dust and flotation concentrate: a comparative study on the stirred tank and airlift reactors.
To scrutinize the influence of the design and type of the bioreactors on the bioleaching efficiency, the bioleaching were evaluated in a batch airlift and a batch stirred tank bioreactors with mixed mesophilic and mixed moderately thermophilic bacteria. According to the results, maximum copper recoveries were achieved using the cultures in the stirred tank bioreactors. It is worth noting that the main phase of the flotation concentrate was chalcopyrite (as a primary sulphide), but the smelter dust mainly contained secondary copper sulphides such as Cu(2)S, CuS, and Cu(5)FeS(4).Under optimum conditions, copper dissolution from the combined flotation concentrate and smelter dust (as an environmental hazard) reached 94.50% in the STR, and 88.02% in the airlift reactor with moderately thermophilic, after 23 days. Also, copper extractions calculated for the bioleaching using mesophilic bacteria were 48.73% and 37.19% in the STR (stirred tank reactor) and the airlift bioreactor, respectively. In addition, the SEM/EDS, XRD, chemical, and mineralogical analyses and studies confirmed the above results.


Implementation of best practice goal-setting in five rehabilitation services: A mixed-methods evaluation study.
This implementation study aimed to enhance the key elements of clinical practice goal-setting across 5 rehabilitation services. This study followed a participatory action research approach guided by the Knowledge to Action framework. Medical record audits and structured client interviews were conducted prior to and following 12 weeks of implementation, in order to evaluate the success of the goal-setting implementation package. Medical record audits and interviews conducted pre-implementation (audits n = 132, interviews n = 64), post-implementation (audits n = 130, interviews n = 56) and at 3-month follow-up (audits n = 30) demonstrated varied success across sites. Following implementation 2 sites significantly improved their common goal focus (site 1 p ≤ 0.001, site 2 p = 0.005), these sites also demonstrated a significant increase in clients reporting that they received copies of their rehabilitation goals (site 1 p ≤ 0.001, site 2 p ≤ 0.001). Four sites improved client action planning, feedback and review, and 3 sites enhanced their specificity of goal-setting. At 3-month follow-up 4 sites had continued to improve their common goal focus; however, all sites decreased the specificity of their goal-setting. Elements of the implementation package were successful at enhancing the goal-setting process; however, how the package is implemented within the team may impact outcomes.


Laparoscopic Nissen versus Toupet fundoplication: objective and subjective results of a prospective randomized trial.
Although symptom outcomes following laparoscopic fundoplication have been adequately evaluated in the past, comparative subjective data of laparoscopic Nissen and Toupet fundoplications are scarce. Multichannel intraluminal impedance monitoring (MII) has not been used so far for comparison of objective data. One hundred patients with documented chronic gastroesophageal reflux disease (GERD) were randomly allocated to either floppy Nissen fundoplication (group I, n = 50) or Toupet fundoplication (group II, n = 50). Gastrointestinal Quality of Life Index (GIQLI), symptom grading, esophageal manometry, and MII data were documented preoperatively and 3 months after surgery. Subjective and objective outcome data were compared to those of healthy individuals. Symptom intensity was significantly more severe and GIQLI showed impairment in the examined patient population compared to healthy controls. Both procedures resulted in a significant improvement in GIQLI and GERD symptoms (p < 0.01). Dysphagia improved significantly only in group II, while cough, asthma, and distortion of taste improved significantly in both groups. Hoarseness symptoms showed some degree of improvement in both groups but reached statistical significance only in group I. Postoperatively, bowel symptoms partly increased and the ability to belch decreased in both groups (p < 0.05). Comparison of postoperative GIQLI and symptom scores showed no significant difference between the two groups, except for the ability to belch, which was more impaired after Nissen fundoplication. Both procedures resulted in a significant improvement in lower esophageal sphincter (LES) pressure; however, the improvement was greater in group I than in group II. MII data showed more reflux control after Nissen, but the differences between the procedures were not significant. Both procedures equally improve quality of life and GERD symptoms. Bowel symptoms may increase after both procedures at the 3-month follow-up. Manometry and MII data favor Nissen fundoplication, but dysphagia and the inability to belch are more common compared to Toupet fundoplication.


Comparative Cardiovascular Safety of Novel Hormonal Agents in Metastatic Castration-Resistant Prostate Cancer Using Real-World Data.
Novel hormonal agents (NHAs) such as abiraterone acetate (ABI) and enzalutamide (ENZ) are frequently used in metastatic castration-resistant prostate cancer (mCRPC). Despite their overall tolerable risk profile, certain signals of cardiovascular toxicity were reported for these agents in clinical trials but little is known about their incidence in clinical practice. The objective was to assess the comparative cardiovascular safety of ABI and ENZ in patients with mCRPC in the real-world. A retrospective population-based cohort was extracted from Quebec public healthcare administrative databases. First-time NHA users between 2011 and 2016 were selected. The primary outcome of interest was cardiovascular-related hospitalization (composite outcome that included acute coronary syndrome, cerebrovascular stroke, heart failure, arrhythmia and others). Inverse probability of treatment weighting (IPTW) with the propensity score was used to adjust for measured baseline characteristics including pre-existing cardiovascular disease. The cohort comprises 2,183 patients, with 1,773 (81.2%) in the ABI group and 410 (18.8%) in the ENZ group. Crude incidence rates of cardiovascular-related hospitalization were of 9.8 events per 100 person-years (PYs) and of 7.1 events per 100 PYs for the ABI and ENZ groups, respectively. The ABI group was at greater risk of cardiovascular-related hospitalization compared to the ENZ group (IPTW-hazard ratio (HR) 1.82; 95% confidence interval (95%CI) 1.09-3.05). The risk of hospitalization for heart failure was greater in ABI (IPTW-HR 2.88; 95%CI 1.09-7.63). Our findings suggest that ABI users may be at greater risk of cardiovascular-related hospitalization compared to ENZ users, in particular for heart failure. These results provide clinicians with additional insight on the cardiovascular risks of mCRPC patients treated with NHAs in the real-world and further large studies are required to corroborate these findings.


The bioavailability of Tamoplex (tamoxifen). Part 3. A steady-state study in breast cancer patients.
The bioavailability of two tamoxifen preparations (Tamoplex and Nolvadex) was compared in a multiple dose two-way cross-over design in twelve breast cancer patients. The formulations were found to be bioequivalent. Mean steady-state serum levels of tamoxifen and N-desmethyltamoxifen were 133 ng/ml and 242 ng/ml, respectively, at a single daily dose of three tablets of Tamoplex 10 mg and 128 ng/ml and 248 ng/ml, respectively, at a single daily dose of three tablets of Nolvadex 10 mg. While there was a large interpatient as well as intrapatient variability in steady-state levels of tamoxifen and N-desmethyltamoxifen, their ratio appeared to be constant in the individual patient.


The 2013 measles outbreak in Sri Lanka: experience from a rural district and implications for measles elimination goals.
Sri Lanka was the first country in the Southeast Asian region to achieve its measles elimination goal in 2011. In 2012, the measles immunization schedule changed from a measles vaccine at 9 months to a measles, mumps and rubella vaccine at 12 months. However in 2013, Sri Lanka reported its worst recent outbreak of measles. This study investigated a part of this outbreak in order to describe its epidemiology. A prospective study was carried out at the university medical unit of the Teaching Hospital, Anuradhapura (THA), the third largest hospital in Sri Lanka, from October 2013 until March 2014. An epidemiological profile of patients was constructed, case confirmation was done on all suspected cases and the basic demographic details of these suspected cases were obtained from the available records. From January 2013 to March 2014, 101 measles suspects were admitted to the THA. Until June 2013, all suspected cases were aged below 12 months of age. During the study period (15 months), the total number of patients aged below 9 months, 9 to 12 months, 1 to 11 years, 12-29 years and over 29 years were 10 (9.9 %), 11 (10.9 %), 6 (5.9 %), 37 (36.6 %) and 36 (35.6 %), respectively (data missing-1). Out of the 33 patients clinically suspected, 32 tested positive for measles. Common clinical features included: fever (n = 33, 100 %), maculopapular rash (n = 33), conjunctivitis (n = 31), posterior cervical lymphadenopathy (n = 23) and Koplik's spots (n = 8). Features suggestive of pneumonia were observed among 30 (90.9 %) patients and 26 (78.8 %) had diarrhoea. Two patients (6.1 %) who developed severe pneumonia received care at an intensive care unit due to respiratory difficulties. Out of 33 patients, 15 (45.5 %) had prior immunization for measles, two (6.1 %) reported that they never had a measles immunization and 16 (48.5 %) were unsure about their immunization status. Out of those who reported they were previously immunized, 11 (73.3 %) belonged to the age group of 12-2 years. Because the first cases of this outbreak were infants, an increase in susceptible infants due to the change in the vaccine schedule could partly explain the outbreak.


Seasonal variation of maximal oxygen consumption rate in humans.
The relationship of maximal oxygen uptake (VO2 max) and resting oxygen uptake in two seasons of the year (winter/summer) was investigated in 119 young males. The subjects were conscripts, who were investigated at the calling-up time (winter: n = 58). The two groups were comparable with respect to their anthropometric data and smoking habits, as well as their occupational and leisure time activities. VO2 max was significantly (p less than 0.01) higher in the subjects investigated in the summer time (3.35 1/min) compared with those in the winter time (3.12 1/min). There was no difference in resting VO2 expressed relatively to body weight, whereas the resting VO2 was significantly (p less than 0.05) higher in winter than in summer, when it was expressed relatively to lean body mass and body surface area. The results suggest that seasonal variation in maximal aerobic power may occur in young males; this may in turn affect their response to physical training.


Factors associated with intensified infection prevention and vaccination practice among Thai health care personnel: A multicenter survey during COVID-19 pandemic.
Intensified infection prevention (IP) and health care personnel (HCP) vaccination programs could enhance HCP safety during COVID-19 pandemic. A multi-center survey regarding on intensified IP practices and vaccination uptake among HCP was performed. Working in the emergency medicine department was associated with wearing a double mask and face shield (P = .04). Despite having more confidence in care of COVID-19 patients, there was no significant improvement of intensified IP practices, COVID-19 and influenza vaccination programs among "high-risk" HCP.


The effect of symmetrical and asymmetrical hearing impairment on music quality perception.
The purpose of this study was to investigate the effect of symmetrical, asymmetrical and unilateral hearing impairment on music quality perception. Six validated music pieces in the categories of classical music, folk music and pop music were used to assess music quality in terms of its 'pleasantness', 'naturalness', 'fullness', 'roughness' and 'sharpness'. 58 participants with sensorineural hearing loss [20 with unilateral hearing loss (UHL), 20 with bilateral symmetrical hearing loss (BSHL) and 18 with bilateral asymmetrical hearing loss (BAHL)] and 29 normal hearing (NH) subjects participated in the present study. Hearing impaired (HI) participants had greater difficulty in overall music quality perception than NH participants. Participants with BSHL rated music pleasantness and naturalness to be higher than participants with BAHL. Moreover, the hearing thresholds of the better ears from BSHL and BAHL participants as well as the hearing thresholds of the worse ears from BSHL participants were negatively correlated to the pleasantness and naturalness perception. HI participants rated the familiar music pieces higher than unfamiliar music pieces in the three music categories. Music quality perception in participants with hearing impairment appeared to be affected by symmetry of hearing loss, degree of hearing loss and music familiarity when they were assessed using the music quality rating test (MQRT). This indicates that binaural symmetrical hearing is important to achieve a high level of music quality perception in HI listeners. This emphasizes the importance of provision of bilateral hearing assistive devices for people with asymmetrical hearing impairment.


Silicosis: Emerging Trends and How to Screen for Early Detection.
National investigations are finding silicosis in young workers. We developed a silicosis case-finding process and conducted follow-up interviews to identify emerging exposure sources. Probable cases were identified through Wisconsin hospital discharge and emergency department data and Wisconsin lung transplant programs. Interviews were attempted with case-patients under age 60. We identified 68 probable silicosis cases and interviewed 4 case-patients. Occupational exposures for cases under age 60 included sandblasting, quarry work, foundry work, coal mining, and stone fabrication. Two stone fabrication workers were diagnosed before age 40. Prevention is critically important to eliminate occupational silicosis. Clinicians should obtain the occupational and exposure history to identify cases of occupational lung disease and notify public health to identify and prevent workplace exposures.


Application of a five-step message development model for food safety education materials targeting people with HIV/AIDS.
Individuals with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome have an increased risk of contracting foodborne illnesses and need to take special precautions regarding food safety. We implemented a five-step model to assess the needs of people with HIV, develop education materials targeted to their needs, and evaluate acceptance of the materials. Needs assessment focus groups (n=8) with HIV-infected people (n=65) and interviews with health care providers (n=18) were conducted to determine motivators and barriers to adopting food safety recommendations. Education materials were developed using needs assessment data, literature on foodborne illnesses, and the Health Belief Model. Acceptability of materials was evaluated by focus groups (n=4) with HIV-infected people (n=32) and a survey of health care providers (n=25). Needs assessment focus group participants expressed resistance to and confusion about many recommendations. Prototype materials were designed to address barriers and motivators. HIV-infected people who reviewed the prototype materials in evaluation focus groups expressed positive attitudes about the materials, and most indicated willingness to follow recommendations. Health care providers were interested in distributing the education materials to their clients. Carefully listening to HIV-infected people and their health care providers, as well as detailed investigation of the literature on foodborne illnesses, contributed to acceptance of the education materials.


Predictive Validity of the Physical Resilience Instrument for Older Adults (PRIFOR).
This study aimed at evaluating the predictive ability of the Physical Resilience Instrument for Older Adults (PRIFOR) for the recovery of frailty, activity of daily living (ADL), and quality of life in older adults suffering from acute health stressors. The longitudinal study was adopted and patients aged 65 and older with Clinical Frailty Scale (CFS) scores between 4 and 6 were included. The PRIFOR was used to assess physical resilience at baseline. Katz ADL, CFS and EuroQoL 5-dimension Questionnaire (EQ5D) scores were all assessed at baseline and one month after discharge. The mean age of the 192 participants was 76.29 ± 6.53 years, and 50.5% were female. After adjusting for the baseline condition, the PRIFOR was only significantly associated with the CFS (β=-0.183, p<0.001) at one month after discharge. Our study results provide evidence of the predictive capacity of the PRIFOR for recovery from frailty.


Comparative cost analysis of implanting devices in different cardiac resynchronization therapeutic strategies.
Cardiac resynchronization therapy (CRT) is an established treatment option for heart failure patients. However, the implementation of triple-chamber pacemakers can be cost-prohibitive. His-Purkinje system pacing (HPSP) can also enable cardiac resynchronization, and it can be achieved with relatively inexpensive conventional pacemakers. This article aims to comparatively evaluate the cost of implanting devices in different CRT strategies to provide meaningful guidance for clinical decision-making by electrophysiologists. Data was collected on the prices, designed life, and price/designed life of multiple mainstream models of CRT-P, CRT-D, dual-chamber pacemakers, and single-chamber pacemakers that were sold in the Chinese market in 2022. The prices, designed lives, and price/designed life of different pacemaker models were then compared. The costs of CRT-P and CRT-D (13008.44 ± 2752.30 USD and 22043.36 ± 3676.25 USD) were significantly higher than those of conventional pacemakers (dual-chamber: 11142.39 ± 4273.85 USD and single-chamber: 5634.28 ± 2032.80 USD) (p < .05). Additionally, the price/designed life of conventional pacemakers (dual-chamber: 839.63 ± 258.62 US dollar/year and single-chamber: 435.86 ± 125.44 US dollar/year) was significantly better than that of CRT-P and CRT-D (1386.91 ± 266.73 and 2585.53 ± 520.27 US dollar/year, respectively) (p < .05). Conduction system pacing (CSP)-based CRT is more cost-effective than BVP-based CRT. Furthermore, CSP-based CRT can achieve cardiac resynchronization with conventional pacemakers and may be a good option for HF patients who do not need defibrillation.


Case-mix adjusted incidence of pressure ulcers in acute medical and surgical wards.
Pressure ulcers cause considerable pain and suffering and are also a very expensive drain on NHS funding. Measuring prevalence is particularly useful for guiding use of resources whereas incidence is an outcome indicator of quality of care. Patients and illnesses vary and it may be misleading to make assumptions based on crude incidence figures. A system of case-mix adjustment has been developed in Glasgow (GPSISS). This study used GPSISS to measure case-mix adjusted incidence of pressure ulcers in over 15,000 acute hospital patients. The incidence of pressure ulcers ranged from 1.1% to 2.7%. These low rates, and the time cost and effort involved in ensuring quality data, suggests that significant differences in quality of care may be demonstrated more quickly using processes rather than outcomes and may more directly identify where changes in practice are required.


Morphological variability of lymphohistiocytic variant of anaplastic large cell lymphoma (former lymphohistiocytic lymphoma according to the Kiel classification).
According to the WHO classification, anaplastic large cell lymphoma (ALCL) is a distinct T-cell lymphoma entity with a number of morphological variants. The characteristic feature of lymphohistiocytic variant of ALCL according to the WHO classification is the abundance of histiocytes that exceed and mask the tumour cell population. In the current, study we reanalysed a historical series of 17 lymphomas, diagnosed as lymphohistiocytic lymphoma according to the criteria of the Kiel classification, with the presence of large purple macrophages (LPM) as the decisive finding for diagnosing this lymphoma subtype. We assessed the cellular composition of the tumour and correlated the results with the definition of lymphohistiocytic variant of ALCL given in the WHO classification. Although all cases in our cohort matched the criteria of ALCL according to the WHO, in 30% of the cases, the total amount of macrophages did not exceed the number of CD30-positive tumour cells. Our results indicate that the presence of LPM might be helpful to identify this subgroup of ALCL. Because the distinction of morphological subtypes of ALCL is of clinical relevance, improved criteria for subtyping ALCL are urgently needed that might include the presence LPM as one criteria.


Effect of timed bright light treatment for rest-activity disruption in institutionalized patients with Alzheimer's disease.
Disturbances in rest-activity rhythm are prominent and disabling symptoms in Alzheimer's disease (AD). Nighttime sleep is severely fragmented and daytime activity is disrupted by multiple napping episodes. In most institutional environments, light levels are very low and may not be sufficient to entrain the circadian clock to the 24-hour day. The purpose of this randomized clinical trial was to test the effectiveness of timed bright light therapy in reducing rest-activity (circadian) disruption in institutionalized patients with AD. The experimental groups received either morning (9.30-10.30 am) or afternoon (3.30-4.30 pm) bright light exposure ( > or = 2500 lux in gaze direction) Monday through Friday for 10 weeks. The control group received usual indoor light (150-200 lux). Nighttime sleep, daytime wake, and rest-activity parameters were determined by actigraphy. Repeated measures analysis of variance was employed to test the primary study hypotheses. Seventy institutionalized subjects with AD (mean age 84) completed the study. No significant differences in actigraphy-based measures of nighttime sleep or daytime wake were found between groups. Subjects in either experimental light condition evidenced a significantly (p < 0.01) more stable rest-activity rhythm acrophase over the 10-week treatment period compared to the control subjects whose rhythm phase delayed by over two hours. One hour of bright light, administered to subjects with AD either in the morning or afternoon, did not improve nighttime sleep or daytime wake compared to a control group of similar subjects. However, exposure to one-hour of bright light in either the morning or afternoon may provide sufficient additional input to the circadian pacemaker to facilitate entrainment to the 24-hour day.


A case of pathologically confirmed streptococcal infection-related IgA vasculitis with associated glomerulonephritis and leukocytoclastic cutaneous vasculitis.
We report the case of an 80 year-old woman who developed bilateral lower extremity purpura and renal impairment with proteinuria a few days after a transient fever (day 0). High levels of both anti-streptolysin-O antibody (ASO) and anti-streptokinase antibody (ASK), as well as low levels of coagulation factor XIII in serum were noted. Skin biopsy was performed and showed a leukocytoclastic vasculitis with deposition of IgA and C3 in the cutaneous small vessels, indicating IgA vasculitis in the skin. After initiation of oral prednisolone, the skin lesions showed significant improvement. However, renal function and proteinuria gradually worsened from day 12. Kidney biopsy was performed on day 29, which demonstrated a necrotizing and crescentic glomerulonephritis with mesangial deposition of IgA and C3. In addition, the deposition of galactose-deficient IgA1 (Gd-IgA1) was positive on glomeruli and cutaneous small vessels, indicating that the purpura and glomerulonephritis both shared the same Gd-IgA1-related pathogenesis. In addition, the association between the acute streptococcal infection and the IgA vasculitis was confirmed by the deposition of nephritis-associated plasmin receptor (NAPlr) in glomeruli. The patient was treated with steroid pulse and intravenous cyclophosphamide, in addition to the oral prednisolone treatment. Renal function and proteinuria gradually improved, but did not completely recover, as is typically seen with courses of IgA vasculitis in the elderly. In this case, the streptococcal infectionrelated IgA vasculitis was confirmed pathologically by the deposition of both NAPlr and Gd-IgA1 in glomeruli, as well as Gd-IgA1 in the cutaneous small vessels.


Speed variability of air-driven motors in the self-threading pin technique.
Effective pin placement is dependent upon correct preparation of the dentine channel. Various factors contribute to the success or otherwise of this channel preparation. One such factor is the rotational speed of the twist drill. It is widely recommended that the twist drill be operated within the 500-800 rpm speed range, in order to prevent a temperature rise in the pulp during the cutting process. This paper examines the ability of air-driven dental motors, when coupled to two speed-reduction handpieces with differing reducing ratios, to operate within this range. The results reveal a wide variation in the speed ranges of the motors tested. Of the two types of handpiece examined, it appears that a 10:1 speed reduction is appropriate for the majority of motors.


Current optometric practices and attitudes in keratoconus patient management.
To compare the current optometric practices and attitudes in the management of keratoconus patients in the UK and Spain. An online survey (adapted to optometric practices) was distributed via a newsletter emailed by various professional organizations in the UK and Spain. Four hundred and sixty-four practitioners (126 in the UK; 338 in Spain) who prescribed gas permeable GP contact lenses (CLs) more than once per month (54.8% of UK practitioners and 28.1% of practitioners in Spain; p<0.01) responded to the questionnaire. A combination of multiple factors is considered necessary in the keratoconus detection (79.4% in the UK, 75% in Spain; p=0.68), and the use of classification criteria is considered relevant (67.5% in the UK, 70.7% in Spain; p=0.49). There is a high consensus on the consideration that GP CL fitting is more difficult in keratoconus (79.4% in the UK, 80.5% in Spain; p=0.79) requiring more diagnostic lenses (3.2±1.4 and 3.4±1.2 in the UK and Spain, respectively; p=0.72) than are necessary for healthy eyes. Using corneal topography is uncommon from both countries (38.1% in the UK, 59.8% in Spain; p<0.01), with a similar ophthalmologist referral pattern (at initial diagnosis, 50% in both the UK and Spain; p=1.00). Few cases of co-management with ophthalmologists were noted (no co-management reported by 60.3% in the UK and 72.8% in Spain, p=0.01). This study provides initial observations and evidence regarding keratoconus management by optometrists in the UK and Spain and shows similarity in the professional practices and attitudes of practitioners in these two countries.


Pathological femur fracture secondary to radiation therapy for soft tissue sarcoma.
Bone fracture is a well known possible late complication of radiation treatment. Little has been written about fractures of long bones after irradiation. We present a case of femur bone necrosis secondary to postoperative radiation for a soft tissue sarcoma of the thigh 20 years earlier. Fixation of the diaphyseal fracture and radiological evolution are described.


Is total laparoscopic surgery for endometrial carcinoma at risk of local recurrence? A long-term survival.
Loco-regional recurrences after laparotomic surgery for early endometrial carcinoma have an incidence of 3-8%. This study examined the pattern of recurrences and survival after full laparoscopic hysterectomy. Between January 1997 and December 2002, 113 consecutive patients with pre-operative Stage I endometrial cancer, self-referred to two different surgical teams, were treated by the laparoscopic approach by one team and by the laparotomic approach by the other team. Nineteen patients were treated by total laparoscopic hysterectomy (TLH) by the endoscopic group, and 94 were treated by total abdominal hysterectomy (TAH) by the oncologic group. Sixteen patients (84.2%) in the laparoscopic group and 79 patients (84.0%) in the laparotomic group had Stage I disease. The mean age and mean weight did not differ in the two groups. With a mean follow-up of 52.2 months for the TLH group and 43.6 months for the TAH group, one recurrence (5.3%) was observed in the former group and 9 recurrences (10.6%) in the latter group. No significative differences were observed for disease-free survival and overall survival. Total laparoscopic hysterectomy does not increase the risk of local recurrence and does not affect survival for patients with early stage endometrial carcinoma.


Serological markers of hepatitis B virus and alpha-fetoprotein levels preceding primary hepatocellular carcinoma in Alaskan Eskimos.
The availability of stored sera that had been obtained for other investigations permitted examination of the sequential development of hepatitis B virus (HBV) infection markers and alpha-fetoprotein (AFP) in persons who later developed primary hepatocellular carcinoma (PHC). 9 of the 11 PHC subjects had markers of HBV infection. The results showed that HBV infection could have occurred as little as 10 years before the recognition of PHC. Seroconversion from HBeAg to anti-HBe and significant rises of AFP levels occurred as long as 6 years and 2 years, respectively, before clinical onset of PHC. The finding that anti-HBe seems to precede the rise in AFP by several years suggests that in populations with a high incidence of HBV-associated PHC, or in families with high risk of PHC, the best use of AFP screening may be to monitor HBsAg carriers after seroconversion from HBeAg to anti-HBe.


Periodontal regeneration risk assessment in the treatment of intrabony defects.
Regenerative approaches performed in periodontics seems to be efficient in treating intrabony defects. There are, however, many factors that may affect the predictability of the regenerative procedures. The present article aimed to propose a new risk assessment tool for treating periodontal intrabony defects by regenerative therapy. Different variables that could affect the success of a regenerative procedure were considered based on their impact on (i) the wound healing potential, promoting wound stability, cells, and angiogenesis, or (ii) the ability to clean the root surface and maintain an optimal plaque control or (iii) aesthetics (risk for gingival recession). The risk assessment variables were divided into a patient, tooth, defect, and operator level. Patient-related factors included medical conditions such as diabetes, smoking habit, plaque control, compliance with supportive care, and expectations. Tooth-related factors included prognosis, traumatic occlusal forces or mobility, endodontic status, root surface topography, soft tissue anatomy, and gingival phenotype. Defect-associated factors included local anatomy (number of residual bone walls, width, and depth), furcation involvement, cleansability, and number of sides of the root involved. Operator-related factors should not be neglected and included the clinician's level of experience, the presence of environmental stress factors, and the use of checklists in the daily routine. Using a risk assessment comprised of patient-, tooth-, defect- and operator-level factors can aid the clinician in identifying challenging characteristics and in the treatment decision process.


In vitro morphogenesis of PANC-1 cells into islet-like aggregates using RGD-covered dextran derivative surfaces.
Substrates bearing low-fouling carboxymethyl dextran (CMD) upon which RGD is covalently grafted were validated to study PANC-1 cell differentiation in serum-free medium. When exposed to RGD-CMD, cells lightly adhered to the surface and formed islet-like aggregates (ILAs) in contact with the surface. PANC-1 were non-adherent on RGE-CMD, CMD, and tissue culture polystyrene surfaces and aggregated in suspension forming ILAs. RGD-CMD resulted in smaller ILAs. Ki67 and CK-19 expression decreased after 3, 7, and 14 days. E-cadherin expression did not change from 3 to 7 days, but decreased after 14 days. For each marker, there was no difference in the expression between the surfaces. After 14 days, ILAs weakly expressed insulin and glucagon and the expression level was independent of the surfaces. No convincing level of insulin or glucagon was detected by immunostaining at 3 and 7 days. A higher level of insulin release was detected in the media after 14 days for cells grown on RGD-CMD. After 14 days, there were three-fold more cells on RGD-CMD surfaces compared to cell numbers found in other culture conditions. α(5) integrin expression was rampant throughout ILAs for all four surfaces. α(V)β(3) integrin expression was only noticeable for ILAs cultured on RGD-CMD surfaces.


Relationship between NF-κB, MMP-9, and MICA expression in pituitary adenomas reveals a new mechanism of pituitary adenomas immune escape.
The aim of this study was to examine the expression levels of NF-κB, MMP-9, and MICA and their relationship between each other in pituitary adenomas as a histological basis for the study of the expression and shedding mechanism of MICA and mechanism of immune escape of pituitary adenomas. Our study indicated that MICA, MMP-9 and NF-κB mRNA and protein levels were more highly expressed in pituitary adenomas than healthy tissues. The expression levels of NF-κB, MMP-9, and MICA were positively related in patients with pituitary adenomas. In conclusion, the activation of NF-κB can up-regulate the expression of MICA and induce the expression of MMP-9, which hydrolyzes MICA into sMICA to promote tumor immune escape. The interactions of NF-κB, MMP-9, and MICA play an important role in the development of pituitary adenomas, and MMP-9 could be used as a new target for inhibiting tumor cell immune escape.


Apoptotic impact of alpha1-blockers on prostate cancer growth: a myth or an inviting reality?
Pharmacological manipulation or genetic targeting of the major apoptosis regulators, such as bcl-2, caspases, and inhibitors of apoptosis (IAPs), represent clinically attractive avenues towards effective therapeutic strategies for advanced prostate cancer. A wealth of evidence established the alpha(1)-adrenoceptor antagonists to be clinically effective in relieving the symptoms associated with benign prostatic hyperplasia (BPH) by relaxing prostatic smooth muscle tone. This action alone however does not fully account for the long-term clinical response to these drugs in BPH patients. Experimental and retrospective clinical studies provided new evidence supporting a differential growth-suppressing function of two alpha(1)-adrenoceptor antagonists against prostate cancer, independent of an alpha(1)-adrenoceptor mechanism. The quinazoline-based antagonists, doxazosin and terazosin, induce apoptosis, inhibit cell adhesion to the extracellular matrix (by activating anoikis), and prevent cell invasion and migration of prostate tumor epithelial cells and vascular endothelial cells. Tamsulosin, a sulphonamide-based, clinically effective alpha(1)-adrenoceptor antagonist for BPH treatment, fails to exert a similar apoptotic action against prostate cells. Furthermore, at pharmacologically relevant doses, doxazosin suppresses benign and malignant prostate growth in in vivo experimental models. The effect is characterized by three intriguing features: (a) it is mediated by an alpha(1)-adrenoceptor-independent action, (possibly related to the quinazoline nucleus); (b) it is targeted at the apoptotic process without affecting cell proliferation; and (c) the elevated apoptotic index correlated with symptom score improvement in BPH patients. This evidence challenges conventional knowledge of the mechanism of action of alpha(1)-adrenoceptor antagonists, and points to a new therapeutic value for these drugs by providing a differential molecular basis for their anti-tumor efficacy. The present review focuses on the characterization of the apoptotic/anti-angiogenic effect of quinazoline-based alpha(1)-adrenoceptor antagonists against prostate cancer cells and discusses the clinical significance of this action in the prevention and treatment of prostate cancer.


The distribution of putative neurotransmitters in the lateral geniculate nucleus of the rat.
Immunocytochemical techniques were used to examine the distribution of several putative peptidergic and aminergic neurotransmitters within the various subdivisions of the rat lateral geniculate nucleus (LG). Neuronal cell bodies, immunoreactive for enkephalin and neuropeptide Y and neuronal fibers immunoreactive for enkephalin, neuropeptide Y, substance P, vasoactive intestinal polypeptide and 5-HT were each localized within distinct subdivisions of the LG. These results suggest that the anatomical and functional differences of LG neurons are also reflected by differences in the transmitters which they utilize.


Functional inactivation of thyroid transcription factor-1 in PCCl3 thyroid cells.
Thyroid transcription factor-1 (TTF-1) is a key regulator of thyroid development and function. In order to identify the genes whose expression depends on TTF-1 transcriptional activity within the thyrocyte we analyzed the consequence of the functional inactivation of this factor in PCCl3 cells. The expression of a fusion protein composed of the DNA binding domain of TTF-1 and of the strong repressive domain of the engrailed protein resulted in a dramatic loss of epithelial cell morphology and in proliferation arrest. These changes were reversed when the inhibition of endogenous TTF-1 was relieved. No change was observed when a similar fusion protein containing point mutations abolishing DNA binding activity was produced in the cells. Besides the expected down-regulation of expression of the main genes linked to the differentiated thyroid function, we observed a decreased expression of the transcription factors Hhex, Pax 8 and TTF-2 and of E-cadherin. By contrast, both ThOX-1 and DUOXA-1 genes were up-regulated, as well as the ones encoding vimentin and several proteins involved in cell cycle arrest. Our data thus extend the known roles of TTF-1 in thyroid development and in the expression of differentiated function in the adult organ to the control of epithelial morphology and of cell division in mature thyrocytes.


Impacts of ammonia stress on different Pacific whiteleg shrimp Litopenaeus vannamei families and the underlying adaptive mechanisms.
Ammonia stress in aquaculture systems poses a great threat to the growth and survival of the Pacific whiteleg shrimp Litopenaeus vannamei. Although the ammonia stress tolerance capacity of L. vannamei has been found to vary significantly among different breeding families, the underneath mechanisms are still largely unknown. In this study, the ammonia tolerance capacity of different L. vannamei breeding families was compared. Results confirmed the significant differences in the ammonia adaptability among different families. To ascertain the underlying adaptive strategies, ATP status, ATP synthase activity, expression and activities of ammonia excretion and metabolism-related enzymes, and apoptosis in shrimp gills were analyzed. Furthermore, transcriptomic analyses were also performed to elucidate the molecular mechanisms. Our results indicated that ammonia-tolerant L. vannamei may possess (1) enhanced ability to excrete ammonia, (2) better capacity to convert ammonia into less toxic products, and (3) sufficient energy reserves for ammonia-compensating processes.


Disciplinary processes for nurses, from organizational supervision to outcomes: A document analysis of a regulatory authority's decisions.
This study aims to explore the disciplinary processes for nurses, from organizational supervision to final decisions by the Finnish regulatory authority. Regulatory authorities are responsible for protecting the public, by ensuring that they receive safe, competent and ethical nursing care, but little is known about the disciplinary processes for nurses. This is a retrospective document analysis of 296 disciplinary decisions by the Finnish regulatory authority from 2007 to 2016. The data were analysed using a quantitative design with descriptive statistics. We studied 204 disciplined nurses (81.4% female) with a mean age of 43.5 years. The disciplinary process comprised organizational supervision, complaints, investigations and decisions. Nurses with substance abuse issues were more likely to face criminal investigations and receive temporary decisions. The process lasted from under 1 month to years and could have profound effects on nurses, colleagues and nurse managers and compromise patient safety. This study identified key factors that could inform the disciplinary processes for nurses. More knowledge is needed about how organisations ensure patient safety when unprofessional conduct is suspected. Retaining nursing professionals is vital due to global shortages, and more attention should be paid to organizational supervision and support for nurses during disciplinary processes.


The genetic animal model of reflex epilepsy in the Mongolian gerbil: differential efficacy of new anticonvulsive drugs and prototype antiepileptics.
Four new anticonvulsive drugs were compared to four prototype antiepileptics regarding their differential efficacy, i.e. against tonic-clonic, myoclonic, and minor seizures, in reflex epilepsy in genetically epileptic gerbils. We distinguished at least three types of drugs: Phenytoin and ralitoline selectively prevented tonic-clonic seizures; the other drugs tested were active against all seizure types. However, carbamazepine and AHR-11748 were predominantly active against tonic-clonic seizures, whereas phenobarbital, valproate, gabapentin, and zonisamide equipotently suppressed both tonic-clonic and myoclonic seizures.


Evaluation of dosimetric characteristics of a ternary nanocomposite based on High Density Polyethylene/Bismuth Oxide/Graphene Oxide for gamma-rays.
This research aims to investigate a ternary nanocomposite based on High Density Polyethylene/ Bismuth Oxide/Graphene Oxide (HDPE/Bi2O3/GO) at various concentrations. Solution method was used to fabricate the samples. FESEM-EDX mapping, AFM, TEM, XRD, XPS, FTIR, and TGA/DTG analyses were carried out on the samples. XRD analysis demonstrated a semi-crystalline behavior for the samples. TEM analysis exhibited a cauliflower-like structure of the material. The sample was irradiated by gamma-rays of 60Co source over the dose rate of 30-254 mGy/min and the electric current was measured as the response of the real-time dosimeter. Thus, various dosimetric characteristics were performed, namely linearity, angular dependence, energy dependence, bias-polarity, field size, and repeatability of the data. Results showed that response of the dosimeter was linear in the range of the investigated dose rate. The sensitivity of the 60 wt% Bi2O3 sample was measured as 3.4 nC·mGy-1. The angular response variation was 20% for normal beam incidence. The response of the dosimeter to assess the energy dependency was obtained as 2.2% at the radiation field of the 137Cs and 60Co beams. The dosimeter response was dependent on the bias-polarity, with maximum discrepancy of 11.1%. The dosimetry response was highly dependent upon the radiation field size. The repeatability of the dosimeter response was measured with standard deviation less than 1%. As well, the dosimeter response during the one-hour irradiation was stable with a standard deviation of 0.66%. Results showed that considering some correction factors, this material can be used for dosimetry of gamma-rays at the therapy level.


Explanations of the endowment effect: an integrative review.
The endowment effect is the tendency for people who own a good to value it more than people who do not. Its economic impact is consequential. It creates market inefficiencies and irregularities in valuation such as differences between buyers and sellers, reluctance to trade, and mere ownership effects. Traditionally, the endowment effect has been attributed to loss aversion causing sellers of a good to value it more than buyers. New theories and findings--some inconsistent with loss aversion--suggest evolutionary, strategic, and more basic cognitive origins. In an integrative review, we propose that all three major instantiations of the endowment effect are attributable to exogenously and endogenously induced cognitive frames that bias which information is accessible during valuation.


Corrigendum: A prosperous application of hydrogels with extracellular vesicles release for traumatic brain injury.
[This corrects the article DOI: 10.3389/fneur.2022.908468.].


Usher's syndrome type III: ENG findings in four affected and six unaffected siblings.
ENG recordings showed abnormal findings in subjects affected by Usher's syndrome and in unaffected siblings. Unaffected subjects with hearing impairment may be heterozygote carriers with inner ears more sensitive to various injurious stimuli, e.g. noise, than those of healthy subjects. Vestibular tests may facilitate the detection of heterozygote carriers but the number of patients studied by us is too small to allow definitive conclusions to be reached.


Gibberellin confers to the expression of TaGA-6D and negatively regulates the fertility of wheat with Aegilops juvenalis cytoplasm.
As the trace signal molecules widely existing in plants, plant hormones can regulate physiological responses of plants at low concentrations. At present, the effect of plant endogenous hormones on wheat male fertility has attracted attention, but the molecular mechanism underlying fertility regulation is unclear. Given this, the anthers of five isonuclear alloplasmic male sterile lines and their maintainer line were RNA-sequenced. A gene TaGA-6D encoding gibberellin (GA) regulated protein was isolated, which was located to the nucleus, cell wall and/or cell membrane, and predominantly highly expressed in the anther of Ju706A, a male sterile line with Aegilops juvenalis cytoplasm. By spraying assay of GA with different concentrations on fertility line Ju706R, it was found that with the increase of exogenous GA concentration, the content of endogenous GA and expression level of TaGA-6D in anther gradually increased, and the fertility decreased. However, silencing of TaGA-6D partially restore the fertility of Ju706R sprayed with 1000 ng/μl GA, and indicating that gibberellin can promote the expression of TaGA-6D and negatively regulates the fertility of wheat with Aegilops juvenalis cytoplasm, which providing new insights for understanding hormone regulation of male fertility in wheat.


Age-dependent differences in cholinergic drug response in two strains of mice.
The behavioral effects of nicotine and oxotremorine were assessed in two strains of mice, C57BL/6 (C57) and DBA/2 (DBA), differing in the ontogeny of forebrain cholinergic structures. Both nicotine and oxotremorine depressed to a higher extent the behavior of DBA mice starting at day 45 of postnatal life.


Preparation and comparative evaluation of sustained release metoclopramide hydrochloride matrix tablets.
Metoclopramide hydrochloride (MCP) is commonly used for the management of gastrointestinal disorders. Frequent administration and the undesired side effects (extra pyramidal symptoms) of the drug on the central nervous system due to the fluctuations of its plasma concentrations may lead to patient incompliance, and hence, improper therapy. Therefore, the present work will be devoted to formulate the drug in sustained release formulations. MCP was incorporated in 12 formulae containing different polymers and/or different polymer ratios. These polymers were hydroxypropylmethyl cellulose (HPMC), carboxymethylcellulose (CMC) and ethyl cellulose (EC). Sodium starch glycolate (SSG) was added to some formulae in different amounts in order to soften and/or disintegrate the tablets. Both direct compression and granulation techniques were used to prepare the tablets. The physical properties were found to be satisfactory for all the formulae. The dissolution profiles of the tablets were constructed using the change-over method. The drug release involved a combination of both diffusion and polymer-chain relaxation mechanisms. The time required to release 50% of MCP ranged from 1.2 to more than 8 h. Direct compression and dry granulation techniques produced sufficient sustaining of the drug release. However, the pellets made by wet granulation released MCP in about 2 h, i.e., pelletization spheronization technique was not effective in sustaining the drug.


Everyday Conflict in Families at Risk for Violence Exposure: Examining Unique, Bidirectional Associations with Children's Anxious- and Withdrawn-Depressed Symptoms.
Exposure to family conflict during childhood increases risk for the development of anxiety and mood problems, though the potential for bidirectionality in this association remains unknown. It is also unclear whether nonviolent family conflict is related to children's anxious- and withdrawn-depressive symptoms within high-risk family contexts, independent of more severe events such as children's exposure to violent victimization. Participants included 1,281 children and their caregivers identified as being at high risk for family violence, interviewed prospectively at ages 6, 8, and 10 about family conflict, children's anxious- and withdrawn-depressive behaviors, and children's victimization experiences. After controlling for cumulative victimization prior to and between each time point, significant cross-lagged, bidirectional associations were identified between family conflict and children's anxious- and withdrawn-depressive symptoms across ages 6 and 8, but not across ages 8 and 10. Invariance testing revealed no differences in model fit between boys and girls and minimal differences depending on whether families were reported for maltreatment prior to recruitment. Findings are partially supportive of a conceptualization of the family-child relationship that is reciprocal, while highlighting the role of daily negative familial interactions, over and above experiences of victimization, in predicting anxious- and withdrawn-depressed symptoms in early and middle childhood.


Expression of LAPTM4B-35: a novel marker of progression, invasiveness and poor prognosis of extrahepatic cholangiocarcinoma.
LAPTM4B was proven to overexpress in hepatocellular carcinoma and relate to differentiation. We immunohistochemically investigated the expression and potential clinicopathological and prognostic significance of LAPTM4B encoded protein, LAPTM4B-35, in extrahepatic cholangiocarcinoma (EHCC) for specimens from consecutive 81 patients. LAPTM4B-35 staining was positive in cancer tissues from 59 patients (72.8%), including 12 with score 1, 22 with score 2 and 25 with score 3. No positive staining was found in non-cancer epithelia. The staining score in cancer tissues was not only significantly associated with TNM staging, histological grade, perineural and lymph node invasion (P<0.05), but also of comprehensive prognostic implications, including integrated estimation with CA19-9. These data established that LAPTM4B-35 positively expressed in a great portion of EHCC and might be a novel molecular maker of progression, invasiveness and poor prognosis.


Silicone replacement arthroplasty for Kienböck's disease.
Thirty-nine patients with Kienböck's disease underwent silicone replacement arthroplasty between 1979 and 1994. The patients were followed-up from 1 to 18 years (mean, 8 years). Sixteen prostheses (41%) have had to be removed, from 1 to 18 years postoperatively (mean, 5.6 years), 15 of them because of pain and silicone synovitis or cysts. It appears that silicone synovitis with cyst formation is an inevitable problem in the wrist after silicone replacement arthroplasty of the lunate, and this procedure is only a temporary solution for Kienböck's disease.


Platelet biology and response to antiplatelet therapy in women: implications for the development and use of antiplatelet pharmacotherapies for cardiovascular disease.
Women are underrepresented in cardiovascular studies, even as their preponderance in the aging population steadily increases. Although concerns have been raised about the differential benefit of antiplatelet medications for women, the propensity for increased bleeding among women has also been recognized. A better understanding of the factors contributing to the observed sex-related differences in platelet biology is warranted. These factors include differences in the frequency and expression of genetic polymorphisms affecting platelet responsiveness to agonists (with and without antiplatelet therapies), which might be obtained through population-based studies and in large controlled clinical trials; inflammatory marker levels and their influence on atherothrombotic risk, and the role of specific hormones in mediating platelet activation and function. Knowledge gained about these mechanistic factors might inform the development of sex-specific antithrombotic treatment regimens that confer optimized safety and efficacy.


Recent progress in electrochemical biosensors based on phenylboronic acid and derivatives.
This review provides an overview of recent progress made in the development of electrochemical biosensors based on phenylboronic acid (PBA) and its derivatives. PBAs are known to selectively bind 1,2- and 1,3-diols to form negatively charged boronate esters in neutral aqueous media and have been used to construct electrochemical glucose sensors because of this selective binding. PBA-modified metal and carbon electrodes have been widely studied as voltammetric and potentiometric glucose sensors. In some cases, ferroceneboronic acid or ferrocene-modified phenylboronic acids are used as sugar-selective redox compounds. Another option for sensors using PBA-modified electrodes is potentiometric detection, in which the changes in surface potential of the electrodes are detected as an output signal. An ion-sensitive field effect transistor (FET) has been used as a signal transducer in potentiometric sensors. Glycoproteins, such as glycated hemoglobin (HbA1c), avidin, and serum albumin can also be detected by PBA-modified electrodes because they contain hydrocarbon chains on the surface. HbA1c sensors are promising alternatives to enzyme-based glucose sensors for monitoring blood glucose levels over the preceding 2-3months. In addition, PBA-modified electrodes can be used to detect a variety of compounds including hydroxy acids and fluoride (F(-)) ions. PBA-based F(-) ion sensors may be useful if reagentless sensors can be developed.


Detection of Leishmania infantum DNA by real-time PCR in canine oral and conjunctival swabs and comparison with other diagnostic techniques.
The use of non invasive sampling, such as collection of conjunctival swabs, as a diagnostic tool for the detection of Leishmania DNA is of interest. The purpose of this study was to evaluate the diagnostic utility of detecting Leishmania infection with the use of conjunctival swab samples in dogs living in a highly endemic area for leishmaniosis and to investigate, for the first time, the presence of Leishmania DNA in oral swabs in the same population. One hundred sixty-three dogs living outdoor and recruited in various provinces of Sicily were studied. Leishmania infantum indirect fluorescent antibody test (IFAT), delayed-type hypersensitivity reaction to leishmanin (DTH) and real-time PCR of blood (BL), lymph node (LN), conjunctival (CS) and oral swab (OS) samples were performed. The positive PCR percentages in LN, CS, OS and BL samples were: 24.5%, 22.1%, 8.7% and 5.5%, respectively. Serological and DTH positive percentages were 27.0% and 73.8%, respectively. Seropositive and LN-PCR positive dogs had a high likelihood to be positive by CS-PCR. The similar positive PCR percentages found in CS and LN samples suggest the use of CS-PCR as non-invasive alternative technique to LN-PCR for the detection of Leishmania infection in dogs. In addition, this study demonstrated, for the first time, the presence of Leishmania DNA in oral swabs in dogs.


[Comparison of bumadizone-, phenylbutazone- and oxyphenbutazone-plasma levels after a single oral dose of phenylbutazone and of bumadizone, respectively (author's transl)].
Bumadizone-calcium-semihydrate and phenylbutazone were given orally to two groups (I and II) consisting of 6 persons each; plasma levels of bumadizone, phenylbutazone and oxyphenbutazone were determined over a period of 384 h. For bumadizone a plasma half-life of 6.9 h was found, maximum plasma levels were reached after 1-6 h varying from 27 to 46 microgram/ml. Phenylbutazone- and oxyphenbutazone-AUC-values were compared between the two groups.


Gene organization in a central DNA fragment of Oenococcus oeni bacteriophage fOg44 encoding lytic, integrative and non-essential functions.
The nucleotide sequence of a DNA fragment previously shown to contain the attachment site (attP) of Oenococcus oeni phage fOg44 (. Arch. Virol. 143, 523-536) has been determined. Sequence analysis indicated that this 6226bp EcoRI fragment harbours an integrase gene, in the vicinity of a direct repeat rich region defining attP, as well as genes encoding a muramidase-related lysin (Lys) and a holin polypeptide (Hol). Transcriptional studies suggested that lys and hol are mainly co-expressed, late in the lytic cycle, from a promotor located upstream of lys. Between the lytic cassette and the phage integration elements three additional open reading frames were found: orf217 and orf252 of unknown function and orf72, the putative product of which bears 32% identity with acidic excisionases from other Gram positive phages. We have established that the first two orfs, as well as the predicted promotor of orf72, are included in a 2143-bp DNA segment missing from the genome of the deletion mutant fOg44Delta2. Although lysogens of fOg44 and fOg44Delta2 exhibited similar properties, each phage produced two distinguishable types of lysogenic strains, differing in inducibility and immunity to other oenophages.


The effect of antibiotic changes during treatment of cystic fibrosis pulmonary exacerbations.
Antibiotics are often changed during treatment of pulmonary exacerbations (PEx) in people with cystic fibrosis (CF) who have a poor clinical response. We aimed to characterize the reasons CF providers change antibiotics and examined the effects of antibiotic changes on lung function recovery. This was a retrospective cohort study using the Toronto CF Database from 2009 to 2015 of adults and children with CF PEx treated with intravenous antibiotics. The co-primary outcome measure was absolute and relative change in forced expiratory lung volume in 1 s (FEV1) at end of treatment and follow-up. Secondary outcome assessed the proportion of patients returning to > 90% or > 100% previous baseline FEV1. A total of 399 PEx were included of which 105 had antibiotic changes. Reasons for antibiotic changes included change in antibiotic route prior to discharge (26%), drug reactions (20%), poor FEV1 response (25%), targeting additional microbes (16%) and lack of symptom improvement (13%). In our multivariable analysis, among non-responders (< 90% FEV1 recovery to baseline or lack of symptom improvement at the interim time point), a change in antibiotics was not associated with any significant difference in absolute or relative FEV1 at end of treatment or at follow-up. Antibiotic change in non-responders was not associated with improved return to 90% or 100% baseline FEV1 at end of treatment or follow-up. Changing antibiotics during CF PEx treatment in those with poor clinical response was not associated with any improved FEV1 response or return to baseline lung function.


Poly(ADP-ribose): novel functions for an old molecule.
The addition to proteins of the negatively charged polymer of ADP-ribose (PAR), which is synthesized by PAR polymerases (PARPs) from NAD(+), is a unique post-translational modification. It regulates not only cell survival and cell-death programmes, but also an increasing number of other biological functions with which novel members of the PARP family have been associated. These functions include transcriptional regulation, telomere cohesion and mitotic spindle formation during cell division, intracellular trafficking and energy metabolism.


Gain of Function of Malate Dehydrogenase 2 and Familial Hyperglycemia.
Genes causing familial forms of diabetes mellitus are only partially known. We set out to identify the genetic cause of hyperglycemia in multigenerational families with an apparent autosomal dominant form of adult-onset diabetes not due to mutations in known monogenic diabetes genes. Existing whole-exome sequencing (WES) data were used to identify exonic variants segregating with diabetes in 60 families from the United States and Italy. Functional studies were carried out in vitro (transduced MIN6-K8 cells) and in vivo (Caenorhabditis elegans) to assess the diabetogenic potential of 2 variants in the malate dehydrogenase 2 (MDH2) gene linked with hyperglycemia in 2 of the families. A very rare mutation (p.Arg52Cys) in MDH2 strongly segregated with hyperglycemia in 1 family from the United States. An infrequent MDH2 missense variant (p.Val160Met) also showed disease cosegregation in a family from Italy, although with reduced penetrance. In silico, both Arg52Cys and Val160Met were shown to affect MDH2 protein structure and function. In transfected HepG2 cells, both variants significantly increased MDH2 enzymatic activity, thereby decreasing the NAD+/NADH ratio-a change known to affect insulin signaling and secretion. Stable expression of human wild-type MDH2 in MIN6-K8 cell lines enhanced glucose- and GLP-1-stimulated insulin secretion. This effect was blunted by the Cys52 or Met160 substitutions. Nematodes carrying equivalent changes at the orthologous positions of the mdh-2 gene showed impaired glucose-stimulated insulin secretion. Our findings suggest a central role of MDH2 in human glucose homeostasis and indicate that gain of function variants in this gene may be involved in the etiology of familial forms of diabetes.


Switching of chiral magnetic skyrmions by picosecond magnetic field pulses via transient topological states.
Magnetic chiral skyrmions are vortex like spin structures that appear as stable or meta-stable states in magnetic materials due to the interplay between the symmetric and antisymmetric exchange interactions, applied magnetic field and/or uniaxial anisotropy. Their small size and internal stability make them prospective objects for data storage but for this, the controlled switching between skyrmion states of opposite polarity and topological charge is essential. Here we present a study of magnetic skyrmion switching by an applied magnetic field pulse based on a discrete model of classical spins and atomistic spin dynamics. We found a finite range of coupling parameters corresponding to the coexistence of two degenerate isolated skyrmions characterized by mutually inverted spin structures with opposite polarity and topological charge. We demonstrate how for a wide range of material parameters a short inclined magnetic field pulse can initiate the reliable switching between these states at GHz rates. Detailed analysis of the switching mechanism revealed the complex path of the system accompanied with the excitation of a chiral-achiral meron pair and the formation of an achiral skyrmion.


Effects of free leucine supplementation and resistance training on muscle strength and functional status in older adults: a randomized controlled trial.
To assess the effect of free leucine supplementation combined with resistance training versus resistance training only on muscle strength and functional status in older adults. This was a randomized, double-blind, placebo-controlled, parallel study with two intervention groups. Thirty older adults were randomly assigned to receive either 10 g leucine/day (leucine group [LG], n=15) or a placebo (control group [CG], n=15), plus resistance training over a 12-week period. Maximal overcoming isometric leg strength, functional status, nutritional status, body composition, health-related quality of life, depression, and dietary intake were assessed at 4 and 12 weeks. Missing data at 12 weeks were handled using mixed models for repeated measurements for data imputation. Twenty-four subjects completed the 4-week assessment and eleven completed the 12-week intervention. Clinically significant gains were found in isometric leg strength at both assessment time points. Analysis of the effect size also showed how participants in LG outperformed those in CG for chair stands and the timed up and go test. No significant changes were observed for the rest of the outcomes. Our combined analysis showed moderate changes in isometric leg muscle strength and certain components of functional status. The magnitude of changes found on these outcomes should be qualified as a positive effect of the concomitant intervention.


Listening fast and slow.
The pattern of response times in conversation can reveal a lot about how people listen to each other. Fast response times not only telegraph eagerness but provide evidence of attending in such a way as to almost finish the other's sentences. In other situations, slow response times are more appropriate, such as when listening prompts deeper reflection, or to leave space for the enjoyment of an inside joke. Here we argue that close relationships are not marked exclusively by one or the other pattern, but by the ability to toggle effortlessly between the two as the conversation demands.


Sofosbuvir-Based Antiviral Therapy Is Highly Effective In Recurrent Hepatitis C in Liver Transplant Recipients: Canadian Multicenter "Real-Life" Experience.
This study evaluates the efficacy, safety, and tolerability of regimens containing sofosbuvir (SOF) in the treatment of hepatitis C virus (HCV) recurrence in all genotypes in patients outside of clinical trials in all Canadian transplant centers. One hundred twenty liver transplantation recipients from across Canada with HCV recurrence were started on SOF-based regimens (SOF + simeprevir ± ribavirin (RBV), n = 53; SOF + pegylated interferon + RBV, n = 25; SOF + RBV, n = 36; and SOF + ledipasvir, n = 6) between January and November 2014. Mean age 58 ± 6.85 years, majority (83%) were genotype 1, male (81%), and treatment experienced (82%). Twenty-seven percent had fibrosing cholestatic hepatitis/early aggressive HCV in the graft, and 48% had F3/4 fibrosis. The primary outcomes included patient and graft survival, on- and end-of-treatment response and sustained virological response at 12 weeks after treatment end (SVR12), and adverse events. One hundred thirteen of 120 (94%) patients were HCV RNA undetectable at end of treatment, and SVR12 was achieved in 102/120 (85%) patients, with 7 relapses, 1 nonresponder, and 10 deaths (liver-related complications). Sixty-three percent had HCV RNA levels below the lower limit of quantification at week 4. Serum creatinine levels remained stable throughout the treatment. Severe anemia occurred in 13% of patients, primarily in RBV-based regimens. Sofosbuvir-based antiviral therapy for HCV recurrence after liver transplantation was well tolerated, with an overall high SVR12 rate (85%) including patients with severe disease recurrence and F3-4 cirrhosis. The response rate was higher (91%) in mild HCV recurrence, suggesting earlier treatment might be beneficial.


Survival disadvantage among Medicaid-insured breast cancer patients treated with breast conserving surgery without radiation therapy.
Clinical studies indicate that breast cancer patients treated with breast conserving surgery (BCS) without radiotherapy (RT) have a greater risk of recurrence and mortality compared to those receiving BCS plus RT. However, this relationship has been underdeveloped among low-income women in the community who may face barriers in accessing adjuvant treatment and post-treatment surveillance. It is possible that the prognostic significance of omission of RT in clinical trials underestimates the significance of risk in the community. Using cancer registry, Medicaid claims, and the Social Security Master Death File, we evaluated receipt of RT in women with early stage breast cancer treated with BCS and mean 6-year overall and cancer-specific survival. Logistic regression was used to assess correlates of RT. The Kaplan-Meier method was used to determine survival by RT status and a multivariate Cox proportional hazards regression was used to evaluate the role of RT status on overall and cause-specific survival. A total of 65% of women received RT, and 82% of the sample survived the study period. Death rates of 16% and 51% were observed among those who did and did not receive RT, respectively (P < 0.001). One-third of women who died from cancer (8 of 24) received radiation. Use of RT was associated with a statistically significant decrease in all-cause (hazard ratio = 0.42, 95% CI 0.21-0.85) and cancer-specific mortality (hazard ratio = 0.22, 95% CI -0.09 to 0.57). Adjuvant radiation following BCS was underused in this sample of poor breast cancer patients. Lack of adjuvant RT may be a proxy for inadequate access to care and poor cancer surveillance after treatment.


Major basic protein as a predictor of preterm labor: a preliminary report.
To determine the association between levels of major basic protein and onset of preterm labor, plasma levels of major basic protein were measured in 13 women from weeks 22 to 41 of gestation. Twelve of the 13 women studied experienced spontaneous onset of labor. All of these women demonstrated a late rise in serum levels of major basic protein characterized by an increase in concentration of 156% +/- 14%. A temporal association between a rise in concentrations of major basic protein and the onset of preterm labor, which was successfully treated with tocolytic agents, was observed in three patients. Increases in major basic protein began 3 to 4 weeks before delivery. The rise in levels of major basic protein was absent in one patient who was delivered of her infant at 30 weeks' gestation after induction of labor with oxytocin. Analysis of these data indicate that a protein marker is associated with the onset of human labor not only at term but also preterm.


[Distribution of enzymes in the stereocilia of the ductus epididymis of rats (author's transl)].
Using unfixed or cryostate sections from aldehyde fixed epididymides of adult rats gamma-glutamyl naphthylamides are hydrolysed in the stereocilia of the principal cells in zone 1A-4B and glycyl-prolyl naphthylamides in those of zone 1B-4A (nomenclature of Reid and Cleland, 1957); this is not the case when other amino acid and peptide naphthylamides are employed. Adenosine triphosphate (ATP) is metabolized by the stereocilia in zone 1a, 2, 3 and 4A and adenosine monophosphate (AMP) in the stereocilia of zone 3-6. With thiamine pyrophosphate (TPP) especially the Golgi apparatus of the principal cells in zone 1B and C, 2 and 3 reacts. In addition ATP, AMP and TPP stain the stereocilia of single epithelial cells outside the zones where all stereocilia react. The AMP pattern allows a further subdivision of zone 3 into 3 A and B. Substrates for the demonstration of alpha- and beta-D-glycosidases, non-specific esterases and alkaline phosphatases are either not hydrolyzed by the stereocilia or the rate of hydrolysis is low.


DMRT proteins and coordination of mammalian spermatogenesis.
DMRT genes encode a deeply conserved family of transcription factors that share a unique DNA binding motif, the DM domain. DMRTs regulate development in a broad variety of metazoans and they appear to have controlled sexual differentiation for hundreds of millions of years. In mice, starting during embryonic development, three Dmrt genes act sequentially to help establish and maintain spermatogenesis. Dmrt1 has notably diverse functions that include repressing pluripotency genes and promoting mitotic arrest in embryonic germ cells, reactivating prospermatogonia perinatally, establishing and maintaining spermatogonial stem cells (SSCs), promoting spermatogonial differentiation, and controlling the mitosis/meiosis switch. Dmrt6 acts in differentiating spermatogonia to coordinate an orderly exit from the mitotic/spermatogonial program and allow proper timing of entry to the meiotic/spermatocyte program. Finally, Dmrt7 takes over during the first meiotic prophase to help choreograph a transition in histone modifications that maintains transcriptional silencing of the sex chromosomes. The combined action of these three Dmrt genes helps ensure robust and sustainable spermatogenesis.


State of the art opioid-sparing strategies for post-operative pain in adult surgical patients.
There are various important implications associated with poorly controlled postoperative pain in the adult surgical patient - this includes cardiopulmonary complications, opioid-related side effects, unplanned hospital admissions, prolonged hospital stay, and the subsequent development of chronic pain or opioid addiction. With the ongoing national opioid crisis, it is imperative that perioperative providers implement pathways for surgical patients that reduce opioid requirements and pain-related complications. In this review, the authors discuss the components of a multimodal opioid-sparing analgesia pathway as it pertains to the perioperative environment. Medications reviewed include gabapentinoids, acetaminophen, non-steroidal anti-inflammatory drugs, ketamine, intravenous lidocaine, dexmedetomidine, and glucocorticoids. The use of peripheral nerve blocks and neuraxial analgesia are also discussed. In appropriate cases, regional anesthetic interventions are extremely useful for postoperative analgesia, including peripheral nerve blocks and neuraxial analgesia and while newer postoperative analgesics have been postulated, the literature on such is presently controversial. Coordinated approaches to pain management are recommended to reduce the need for opioids and to improve patient satisfaction post-surgery.


Protein phosphatase 2A interacts with the Na,K-ATPase and modulates its trafficking by inhibition of its association with arrestin.
The P-type ATPase family constitutes a collection of ion pumps that form phosphorylated intermediates during ion transport. One of the best known members of this family is the Na⁺,K⁺-ATPase. The catalytic subunit of the Na⁺,K⁺-ATPase includes several functional domains that determine its enzymatic and trafficking properties. Using the yeast two-hybrid system we found that protein phosphatase 2A (PP2A) catalytic C-subunit is a specific Na⁺,K⁺-ATPase interacting protein. PP-2A C-subunit interacted with the Na⁺,K⁺-ATPase, but not with the homologous sequences of the H⁺,K⁺-ATPase. We confirmed that the Na⁺,K⁺-ATPase interacts with a complex of A- and C-subunits in native rat kidney. Arrestins and G-protein coupled receptor kinases (GRKs) are important regulators of G-protein coupled receptor (GPCR) signaling, and they also regulate Na⁺,K⁺-ATPase trafficking through direct association. PP2A inhibits association between the Na⁺,K⁺-ATPase and arrestin, and diminishes the effect of arrestin on Na⁺,K⁺-ATPase trafficking. GRK phosphorylates the Na⁺,K⁺-ATPase and PP2A can at least partially reverse this phosphorylation. Taken together, these data demonstrate that the sodium pump belongs to a growing list of ion transport proteins that are regulated through direct interactions with the catalytic subunit of a protein phosphatase.


Quantifying mortality burden in patients with cancer due to COVID-19 in the US: A national cross-sectional analysis.
There is limited information on the impact of certain social factors on mortality outcomes in patients with cancer and COVID-19 on a national scale. This study aims to characterize excess mortality and analyze a subset of sociodemographic trends in COVID-19 and cancer mortality. Patients with cancer listed on their death certificates from 2018 to 2021 and patients with COVID-19 and cancer listed on multiple cause of death certificates from the CDC Wide-Ranging Online Data for Epidemiologic Research database from March 2020 to December 2021 were included. Age-adjusted mortality rates (AAMR) per 1,000,000 population were compared across race/ethnicity groups, sex, and census regions. Crude mortality rates were compared across different age groups and regions based on urbanization status. Average AAMR in patients with COVID-19 and cancer was 41.7 in 2020 and 56.7 in 2021. Mortality rates in patients with cancer and COVID-19 were significantly higher in certain populations. Targeted interventions are necessary to improve outcomes.


Bladder carcinogenesis in rats subjected to ureterosigmoidostomy and treated with L-lysine.
to evaluate the effect of L-lysine in the bladder and intestinal epithelia in rats submitted to vesicosigmoidostomy. we divided forty Wistar rats into four groups: group I - control group (Sham); group II - submitted to vesicosigmoidostomy and treated with L-lysine 150mg/kg; group III - submitted only to vesicosigmoidostomy; and group IV - received L-lysine 150mg/kg. After eight weeks the animals were sacrificed. in the bladders of all operated animals we observed simple, papillary and nodular hyperplasia of transitional cells, transitional cell papillomas and squamous metaplasia. As for the occurrence of aberrant crypt foci in the colons of operated animals, we did not observe statistically significant differences in any of the distal, proximal and medium fragments, or in all fragments together (p=1.0000). Although statistically there was no promotion of carcinogenesis in the epithelia of rats treated with L-lysine in the observed time, it was clear the histogenesis of bladder carcinogenesis in its initial phase in all operated rats, this being probably associated with chronic infection and tiny bladder stones. o objetivo deste trabalho é avaliar o efeito da L-lisina nos epitélios vesical e intestinal de ratas submetidas à vesicossigmoidostomia. quarenta ratas Wistar, foram divididas em quatro grupos: grupo I- grupo controle (Sham); grupo II- submetido à vesicossigmoidostomia e tratado com L-lisina 150mg/kg; grupo III- submetido apenas à vesicossigmoidostomia; e grupo IV- recebeu L-lisina 150mg/kg. Após oito semanas os animais foram sacrificados. na bexiga de todos os animais operados observou-se hiperplasia simples, papilar e nodular de células transicionais, papiloma de células transicionais e metaplasia escamosa. Quanto à ocorrência de focos de criptas aberrantes nos colos dos animais operados, não foi evidenciado diferença estatística significante em nenhum dos fragmentos distal, proximal e médio, e todos juntos (P=1,0000). apesar de, estatisticamente, não ter havido promoção de carcinogênese nos epitélios dos ratos tratados com L-lisina, no tempo observado, é nítida a histogênese da carcinogênese de bexiga em sua fase inicial, no epitélio vesical, em todos os ratos operados, estando esta provavelmente associada à infecção crônica e aos diminutos cálculos vesicais.


Comparative Transcriptome Analysis of the Less-Dormant Taiwanese Pear and the Dormant Japanese Pear during Winter Season.
The flower bud transcriptome in the less dormant Taiwanese pear 'Hengshanli' and high-chilling requiring Japanese pear strain TH3 subjected to the same chilling exposure time were analyzed during winter using next-generation sequencing. In buds sampled on January 10th and on February 7th in 2014, 6,978 and 7,096 genes, respectively, were significantly differentially expressed in the TH3 and 'Hengshanli' libraries. A comparative GO analysis revealed that oxidation-reduction process (biological process) and ATP binding (molecular function), were overrepresented during the ecodormancy period (EP) when compared to the endodormancy deepest period (DP), indicating that ATP synthesis was activated during the transition between these dormancy stages. Among the 11 differently expressed genes (DEGs) annotated as probable dehydrins or LEA protein-related genes, 9 DEGs showed higher transcript levels in the DP than in the EP. In order to focus on transcription factors induced by low temperature or drought, 7 differently expressed genes (DEGs) annotated as probable ICE1 or DREB proteins were analyzed by real-time PCR. Expression levels of 3 genes were higher in TH3 than in 'Hengshanli' on all sampling days. Their expression increased during the endodormancy deepest period (DP) and then decreased before endodormancy breaking in TH3 buds. Taken together, these results suggest that these genes annotated as ICE1, DREB and ERF are involved in endodormancy maintenance and in the transition from endodormancy to ecodormancy.


The signaling relations between three adaptors of porcine C-type lectin receptor pathway.
As one family of pattern recognition receptors (PRRs), The C-type lectin receptors (CLRs) play a key role in the anti-fungal infection. The CLR pathway signaling is relayed by adaptor complex which comprises CARD9, BCL10 and MALT1. However, the relationship between these three adaptors has not been investigated. In this study, we isolated porcine CARD9, BCL10 and MALT1 and examined their signaling functions. The three ectopic adaptors were similarly and uniformly expressed in cytoplasm, with CARD9 inactive, BCL10 significant active, and MALT1 slightly active for downstream NF-κB signaling and gene expressions. With the three adaptors together, NF-κB signaling and gene expressions were strongly activated, however, no IFN signal was activated in any case. The signaling relationship between the adaptors were dissected, the NF-κB signaling results showed that CARD9 could inhibit both BCL10 and MALT1 activities, while BCL10 and MALT1 synergized each other particularly when moderate amount of BCL10 plus low amount of MALT1 were considered. Low amount of CARD9 could further synergized with BCL10 and MALT1, maximizing signaling activity of the adaptor complex. This study revealed the porcine CLR pathway adaptor signaling functions and their optimal collective activity, thus providing a unique insight into the porcine innate immunity.


Induction of cardiac angiotensin I-converting enzyme with dietary NaCl-loading in genetically hypertensive and normotensive rats.
We have recently shown that the angiotensin I converting enzyme (ACE) gene is linked to NaCl-loaded blood pressure in the stroke-prone spontaneously hypertensive rat (SHRSP), and that high-NaCl loading selectively stimulates ACE in the aorta of SHRSP but not in normotensive Wistar-Kyoto (WKY) rats. We therefore investigated the relationship between cardiac ACE and the development of hypertension and left ventricular hypertrophy in response to normal- and high-NaCl diet in these rats. ACE mRNA and ACE activity were measured in left ventricular tissue after completion of hemodynamic characterization of the animals. While SHRSP rats increased blood pressure (P < 0.0001) and heart rate (P < 0.005) in response to high NaCl, blood pressure remained unchanged in WKY. Similarly, relative left ventricular weight increased only in SHRSP after high NaCl (P < 0.002). A significant two- to threefold increase of cardiac ACE mRNA and fourfold stimulation of ACE enzyme activity in response to high NaCl was found in both WKY and SHRSP rats (P < 0.005). The induction of ACE gene expression was significantly more pronounced in SHRSP compared to WKY (P < 0.02), whereas no significant strain differences in left ventricular ACE activity were found after either normal- or high-NaCl diet. Thus, arterial blood pressure and left ventricular weight remained unchanged in the WKY rats despite the activation of left ventricular ACE activity after high-NaCl exposure. These results demonstrate that left ventricular ACE activity is equally upregulated in response to high-NaCl in the normotensive and hypertensive strain, independently from the development of hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)


Strategies to improve the photothermal capacity of gold-based nanomedicines.
The plasmonic photothermal properties of gold nanoparticles have been widely explored in the biomedical field to mediate a photothermal effect in response to the irradiation with an external light source. Particularly, in cancer therapy, the physicochemical properties of gold-based nanomaterials allow them to efficiently accumulate in the tumor tissue and then mediate the light-triggered thermal destruction of cancer cells with high spatial-temporal control. Nevertheless, the gold nanomaterials can be produced with different shapes, sizes, and organizations such as nanospheres, nanorods, nanocages, nanoshells, and nanoclusters. These gold nanostructures will present different plasmonic photothermal properties that can impact cancer thermal ablation. This review analyses the application of gold-based nanomaterials in cancer photothermal therapy, emphasizing the main parameters that affect its light-to-heat conversion efficiency and consequently the photothermal potential. The different shapes/organizations (clusters, shells, rods, stars, cages) of gold nanomaterials and the parameters that can be fine-tuned to improve the photothermal capacity are presented. Moreover, the gold nanostructures combination with other materials (e.g. silica, graphene, and iron oxide) or small molecules (e.g. indocyanine green and IR780) to improve the nanomaterials photothermal capacity is also overviewed.


Phospho-ERK staining is a poor indicator of the mutational status of BRAF and NRAS in human melanoma.
Mutated BRAF and NRAS are suspected to contribute to melanomagenesis by activation of extracellular signal-regulated kinase (ERK). To test this notion, we analyzed the presence of phosphorylated ERK1/2 in 170 melanomas with established NRAS/BRAF mutational status and well-documented clinical follow-up by immunohistochemistry. Several notable observations were obtained: (i) phospho-ERK staining was very heterogeneous within the tumor; (ii) in most cases, ERK was phosphorylated in only a minority of tumor cells; (iii) the percentage of phospho-ERK-positive cells was not correlated with the mutational status of NRAS and/or BRAF; (iv) the Raf kinase inhibitor protein (RKIP) was expressed homogeneously in virtually all melanoma samples not reflecting the inhomogeneity of phospho-ERK; and, finally, (v) neither the portion of phospho-ERK-positive tumor cells nor the RKIP staining intensity showed any correlation to the clinical course of the patients. Furthermore, the ability of BRAF mutant melanoma cells to downregulate mitogen-activated protein kinase activation was shown in melanoma cell lines cultured at high densities or under nonadherent conditions. Our findings suggest that mitogen-activated protein kinase (MAPK) activity is subject to regulation even in BRAF/NRAS mutant melanoma cells and that high MAPK pathway signaling may be important only in distinct subsets of tumor cells.


Cigarette smoking-induced acute eosinophilic pneumonia: A case report.
Acute eosinophilic pneumonia (AEP) is a rare pulmonary disease, which is characterized by diffuse pulmonary eosinophilia. The pathogenesis remains unknown. Here we report a patient with AEP following a recently acquired habit of smoking. A 21-year-old female presented with fever, dry cough, and acute hypoxic respiratory distress for 2 days. Chest computed tomography showed bilateral ground glass opacities, patchy nodules, and pleural effusions. Blood tests showed a gradually raised peripheral eosinophils level. Bronchoalveolar lavage fluid revealed marked elevation of eosinophils. She was diagnosed with AEP. Systemic methylprednisolone was immediately used for treatment. Her clinical symptoms and chest radiographs improved promptly after treatment. Cigarette smoking might be an underlying triggering factor of AEP. Diffuse alveolar infiltrates and a gradually increasing peripheral eosinophilia should raise the concern especially in recent smoking patients.


Implementation of Network for the Improvement of Addiction Treatment (NIATx) Processes in Substance Use Disorder Treatment Centers.
Internal process improvements embedded within the Network for Improvement of Addiction Treatment (NIATx) program are promising innovations for improving substance use disorder (SUD) treatment performance, such as engagement and retention. To date, few studies have examined the variables that may increase diffusion and implementation of NIATx innovations. This study investigates organizational characteristics associated with SUD treatment center utilization of NIATx process improvements in a sample of 458 treatment programs. Overall, 19% had utilized NIATx process improvements. After statistically controlling environmental factors, five organizational variables were associated with the likelihood that treatment centers used NIATx processes. Organization size, administrative intensity, membership in a provider association, and participation in National Institute on Drug Abuse's Clinical Trials Network were positively associated with the odds of utilizing NIATx processes, while the association for the level of slack resources was negative. The findings suggest that policies and related supportive efforts may be required to facilitate diffusion and implementation of NIATx processes to affect SUD treatment center performance and capacity.


Prolonged insulin resistance following insulin-induced hypoglycaemia.
Nineteen normal male volunteers underwent a 10-h glucose clamp study to examine the duration and mechanism of insulin resistance after hypoglycaemia. Dextrose delivery by the Biostator to maintain the target blood glucose level fell below baseline 2 h after induction of hypoglycaemia and remained suppressed for at least 7 h after insulin hypoglycaemia. Insulin secretion as manifested by C-peptide levels remained suppressed for 3-4 h after insulin hypoglycaemia despite return of blood glucose to baseline by 90 min. Glucose kinetic data (3-3H-glucose) performed in six of the subjects indicated that the prolonged insulin resistance was due to significantly increased hepatic glucose production and to suppressed glucose utilisation, persisting for at least 4 h after counterregulatory hormone levels had returned to normal. Post-hypoglycaemic insulin resistance as determined by dextrose delivery was markedly attenuated and the rise in hepatic glucose output totally eliminated in five hypopituitary subjects without growth hormone or cortisol responses to hypoglycaemia. We conclude that post-hypoglycaemic insulin resistance occurs in non-diabetic subjects and persists for at least 7 h following hypoglycaemia. This prolonged insulin resistance is largely related to release of growth hormone and cortisol.


[Idiopathic neuroarthropathy in a woman (author's transl)].
The authors report a case of idiopathic and sporadic neuroarthropathy in a 53 year - old woman and point out the rarety of the disease in women unstead of familial Thevenard disease and diabetic neuroarthropathy.


Deletion of synapsins I and II genes alters the size of vesicular pools and rabphilin phosphorylation.
Previous studies established that genetic deletion of synapsins, synaptic vesicle-associated phosphoproteins that regulate neurotransmitter release, decreases the number of synaptic vesicles in nerve terminals. To investigate whether these changes affect the release properties of the remaining synaptic vesicles, we used a radioactive labeling technique to measure release independently of the total number of synaptic vesicles. 3H-glutamate and 14C-gamma-amino-butyric-acid (GABA) release from isolated nerve terminals prepared from the neocortex of synapsins I and II double knock-out mice (DKO) was assayed and compared to wild-type preparations. Hyperosmotic shock-evoked 3H-glutamate was reduced by 20+/-3% from DKO nerve terminals and potassium depolarization-evoked glutamate release was also decreased by 28+/-2%. Surprisingly, sucrose or potassium depolarization-evoked release of 14C-GABA was increased by 32+/-4% and 29+/-5%, respectively. The basal efflux of both 3H-glutamate and 14C-GABA increased by 17+/-2% and 12+/-2% from DKO nerve terminals. As lack of synapsins I and II, major phosphoproteins of synaptic vesicles, may lead to deregulation of phosphorylation events, we compared phosphorylation state of another synaptic vesicle protein, rabphilin. In DKO nerve terminals, membrane-associated rabphilin level was reduced by approximately 0.28-fold, its phosphorylation at 234serine was increased by approximately 1.61-fold whereas cytosolic rabphilin levels showed both more dramatic reduction in abundance, approximately 16.5-fold, and increase in phosphorylation, approximately 4.8-fold. Collectively, these data suggest that deletion of major synapsin isoforms leads to (1) deregulation of basal neurotransmission causing "leaky" basal release, (2) changes in either the size or mobilization of releasable or reserve pools, and (3) a decrease in rabphilin abundance accompanied by an increase in basal phosphorylation of the remaining rabphilin.


Accidental hypothermia and frost-bite in Antarctica.
Two members of an Australian Antarctic expedition suffered hypothermia and frost-bite when they were stranded onshore after their small boat was swamped. Their efforts at field survival until recovery, six hours later, are described. At rescue one patient was found to have frost-bite and a core temperature of 30 degrees C. He was treated successfully by rapid rewarming in a hot bath. The other victim was considerably less hypothermic and suffered only mild frost-bite. Contrary to expectations the tall thin patient fared much better than the short heavier one. Possible explanations for this difference are discussed.


Detection of vigilance performance using eye blinks.
Research has shown that sustained attention or vigilance declines over time on task. Sustained attention is necessary in many environments such as air traffic controllers, cyber operators, and imagery analysts. A lapse of attention in any one of these environments can have harmful consequences. The purpose of this study was to determine if eye blink metrics from an eye-tracker are related to changes in vigilance performance and cerebral blood flow velocities. Nineteen participants performed a vigilance task while wearing an eye-tracker on four separate days. Blink frequency and duration changed significantly over time during the task. Both blink frequency and duration increased as performance declined and right cerebral blood flow velocity declined. These results suggest that eye blink information may be an indicator of arousal levels. Using an eye-tracker to detect changes in eye blinks in an operational environment would allow preventative measures to be implemented, perhaps by providing perceptual warning signals or augmenting human cognition through non-invasive brain stimulation techniques.