A new methodology to calculate the environmental protection index (Ep). A case study applied to a company producing composite materials.
Environmental indicators can be used as a first stage in progress towards comprehensive environmental impact measures [J. Environ. Manage 65/3 (2002) 285]. In this article, we develop a 'pollutant interaction matrix method' that allows calculation of a global environmental protection index (Ep) in order to verify the eco-compatibility of an industrial activity. Two methods are proposed for the Ep index evaluation (which represents the numerical measure of the environmental sustainability): the Direct Method (Epd) and the Weighted Method (Epw). Both methods need to define, in the whole industrial process, homogeneous sectors (defined as construction sites where activities of the same type are carried out). Furthermore, for each activity a set of parameters (t, duration of pollution effect, P, quantity of pollutant produced,G, hazard of the pollutant) are required to evaluate the relative pollution index Y. All indices calculations were carried out using a set of matrices. The correct use of Ep evaluation provides an improvement in the total environmental performance of companies because it points out possible critical operations in each homogeneous sector which require solutions. The methodology is applied to evaluate the environmental pollution risk of a company that produces polymer materials and to improve their environmental performance. The results obtained show that the whole productive process has a low environmental impact factor. Nevertheless the applied methodology puts in evidence some processes that generate local pollution in specific areas of the factory and which could be dangerous for the workers' health.


Perceptions, Knowledge and Attitudes among Young Adults about Prevention of HPV Infection and Immunization.
Human papilloma virus (HPV) is one of the most common sexually transmitted infections and is widely known as the main causative agent for cervical cancer. The aim of this study was to investigate the perceptions, knowledge and attitudes of young Greek adults concerning prevention of HPV infection and HPV immunization. This constitutes a cross-sectional online survey. A convenience sample of young Greek adults (n = 883) residing in Greece, aged 17 to more than 35 years was surveyed from December 2020 to March 2021. Two validated questionnaires were used to collect data. Participants demonstrated moderate knowledge about HPV infection and vaccination, with a mean knowledge score of 53.26 (SD ± 20.65) and 38.92 (SD ± 17.58), respectively. Cronbach's alpha value was 0.77 and 0.80. Female participants were better informed than males. Approximately 52.3% of respondents had been vaccinated and 65.5% were willing to get vaccinated in the future. Vaccination rate was significantly associated with gender (OR = 11.99; 99% CI = 6.59-21.84), knowledge about the HPV vaccine (OR = 1.04; 99% CI = 1.03-1.04) and age (OR = 0.07; 99% CI = 0.03-0.15). Reasons for vaccine refusal were insufficient information (36.8%) and fear of side effects (19%). Correlates of positive vaccination intention were knowledge about HPV (OR = 1.02; 99% CI = 1.01-1.02). The findings suggest that the Greek government's continuing HPV promotion efforts and education on the risks of HPV infection among young people are likely to increase vaccination acceptance among this group.


Does previous stroke modify the relationship between inflammatory biomarkers and clinical endpoints in CKD patients?
Chronic kidney disease (CKD) is an independent risk factor for stroke. Stroke is also an independent risk factor for worse CKD outcomes and inflammation may contribute to this bidirectional relationship. This study aims to investigate inflammatory biomarkers in patients with non-dialysis CKD (ND-CKD) with and without stroke. A propensity matched sample from > 3000 Salford Kidney Study (SKS) patients, differentiated by previous stroke at study recruitment, had stored plasma analyzed for interleukin- 6 (IL-6), Von Willebrand Factor (VWF) and C-reactive protein (CRP). Multivariable cox regression analysis investigated associations between inflammation and death, end-stage renal disease (ESRD) and future non-fatal cardiovascular events (NFCVE). A total of 157 previous stroke patients were compared against 162 non-stroke patients. There were no significant differences in inflammatory biomarkers between the two groups. Previous stroke was associated with greater mortality risk, hazard ratio (HR) (95% CI) was 1.45 (1.07-1.97). Higher inflammatory biomarker concentrations were independently associated with death but not ESRD or NFCVE in the total population. For each 1 standard deviation (SD) increase in log IL-6, VWF and CRP, the HR for all-cause mortality were 1.35 (1.10-1.70), 1.26 (1.05-1.51) and 1.34 (1.12-1.61), respectively. CRP retained its independent association (HR 1.47 (1.15-1.87)) with death in the stroke population. Previous stroke is an important determinant of mortality. However, the adverse combination of stroke and ND-CKD does not seem to be driven by higher levels of inflammation detected after the stroke event. Biomarkers of inflammation were associated with worse outcome in both stroke and non-stroke ND-CKD patients. 15/NW/0818 .


Presence of Intracardiac Thrombus at the Time of Left Ventricular Assist Device Implantation Is Associated With an Increased Risk of Stroke and Death.
Heart failure predisposes to intracardiac thrombus (ICT) formation. There are limited data on the prevalence and impact of preexisting ICT on postoperative outcomes in left ventricular assist device patients. We examined the risk for stroke and death in this patient population. We retrospectively studied patients who were implanted with HeartMate (HM) II or HM3 between February 2009 and March 2019. Preoperative transthoracic echocardiograms, intraoperative transesophageal echocardiograms and operative reports were reviewed to identify ICT. There were 525 patients with a left ventricular assist device (median age 60.6 years, 81.8% male, 372 HMII and 151 HM3) included in this analysis. An ICT was identified in 44 patients (8.4%). During the follow-up, 43 patients experienced a stroke and 55 died. After multivariable adjustment, presence of ICT increased the risk for the composite of stroke or death at 6-month (hazard ratio [HR] 1.82, 95% confidence interval [CI] 1.00-3.33, P = .049). Patients with ICT were also at higher risk for stroke (HR 2.45, 95% CI 1.14-5.28, P = .021) and death (HR 2.36, 95% CI 1.17-4.79 P = .016) at 6 months of follow-up. The presence of ICT is an independent predictor of stroke and death at 6 months after left ventricular assist device implantation. Additional studies are needed to help risk stratify and optimize the perioperative management of this patient population.


Nurses' experiences of managing COVID-19 contact tracing clinics in a tertiary care hospital.
The COVID-19 pandemic spread rapidly globally, making the WHO to declare it a public health emergency of international concern. The ability of health institutions to screen and test for COVID-19 has been critical in detecting, preventing, and managing the spread of the disease. This report documents lessons from the ambulatory care nursing for COVID-19 contact tracing at a tertiary care hospital. In March 2020, a multidisciplinary team consisting of staff of the Primary Healthcare Services, Ambulatory Care Center, Infection Prevention and Control Department, and Nursing Services at the Ministry of National Guard Health Affairs in Riyadh, Saudi Arabia, worked collaboratively to establish 2 dedicated COVID-19 contact tracing clinics away from hospital premises, one clinic established for the public and another for hospital staff. Surveillance system was established to detect and contain as many cases as possible. This report highlights the process of establishing and maintaining the structure and managing workflow of the contact tracing clinics. We calculated the number of nasopharyngeal swabs and the daily average number of patient visits for both clinics between March 2020 and March 2021. Over the one-year period, the clinics served 79 146 visitors with an average of 52 visits for staff, 159 visits for adults, and 16 visits for children per day. The 2 clinics conducted 73 924 polymerase chain reaction tests. There was zero transmission of COVID-19 infection to staff working at both clinics. Despite the challenge of setting up contact tracing clinics, the decision to use separate geographic locations contributed to reducing the risk of infection exposure among staff of the clinics. Effective implementation of contact tracing interventions relies on interdepartmental cooperation and effective communication to contain the risk of viral spread.


Temperature dependence of the SARS-CoV-2 affinity to human ACE2 determines COVID-19 progression and clinical outcome.
The SARS-CoV-2 virus and its homolog SARS-CoV penetrate human cells by binding of viral spike protein and human angiotensin converting enzyme II (ACE2). SARS-CoV causes high fever in almost all patients, while SARS-CoV-2 does not. Moreover, analysis of the clinical data revealed that the higher body temperature is a protective factor in COVID-19 patients, making us to hypothesize a temperature-dependent binding affinity of SARS-CoV-2 to human ACE2 receptor. In this study, our molecular dynamics simulation and protein surface plasmon resonance cohesively proved the SARS-CoV-2-ACE2 binding was less affinitive and stable under 40 °C (~18 nM) than the optimum temperature 37 °C (6.2 nM), while SARS-CoV-ACE2 binding was not (6.4 nM vs. 8.5 nM), which evidenced the temperature-dependent affinity and explained that higher temperature is related to better clinical outcome. The decreased infection at higher temperature was also validated by pseudovirus entry assay using Vero and Caco-2 cells. We also demonstrated the structural basis of the distinct temperature-dependence of the two coronaviruses. Furthermore, the meta-analysis revealed a milder inflammatory response happened in the early stage of COVID-19, which explained the low fever tendency of COVID-19 and indicated the co-evolution of the viral protein structure and the inflammatory response. The temperature dependence of the binding affinity also indicated that higher body temperature at early stages might be beneficial to the COVID-19 patients.


[Function of single channel electrocardiograph is expanded in community medical service].
The paper introduces a designing idea and a carrying-out scheme about expanding functions of single channel electrocardiograph in Chinese community medical service and looks forward to its applying prospects.


How baby's first shot determines the development of maternal attitudes towards vaccination.
The attitude towards vaccination is a major determinant of vaccination behavior; this also includes parents' attitudes towards the immunization of their child. Negative attitudes have been associated with vaccine hesitancy and outbreaks of infectious diseases throughout the globe. This study aimed to assess how and why attitudes become more pro-vaccine or vaccine-skeptical over time, and which sources are especially influential in this process. Prospective cohort study with measurements at time of recruitment during pregnancy and at +3, +6 and +14 months after childbirth with cross-sectional control groups. In total, 351 women entered the longitudinal analyses, while 204, 215 and 173 women were recruited in the cross-sectional control groups, respectively. Inclusion criteria were: (i) being at least 18 years of age, (ii) pregnant, (iii) primigravida, and (iv) living in Germany. During pregnancy mothers reported rather positive prior experiences with vaccinations. However, their judgment turned significantly more negative after the first vaccination experience with their child. Mixed-effects models showed that these changes were significantly related to increased risk perceptions and concerns about vaccination, which then had a negative impact on the vaccination attitude. In contrast, gaining more vaccine-related knowledge over time positively influenced attitude formation. During the first year of their child's life maternal attitudes towards vaccination are formed and guide future decisions whether to vaccinate or not vaccinate a child. Strategies should be implemented that improve mothers' experiences when their newborn is vaccinated to prevent the development of vaccine hesitancy.


Quantum halo states in two-dimensional dipolar clusters.
A halo is an intrinsically quantum object defined as a bound state of a spatial size which extends deeply into the classically forbidden region. Previously, halos have been observed in bound states of two and less frequently of three atoms. Here, we propose a realization of halo states containing as many as six atoms. We report the binding energies, pair correlation functions, spatial distributions, and sizes of few-body clusters composed by bosonic dipolar atoms in a bilayer geometry. We find two very distinct halo structures, for large interlayer separation the halo structure is roughly symmetric and we discover an unusual highly anisotropic shape of halo states close to the unbinding threshold. Our results open avenues of using ultracold gases for the experimental realization of halos composed by atoms with dipolar interactions and containing as many as six atoms.


Validation of myasthenia gravis diagnosis in the older Medicare population.
Administrative health data has been increasingly used to study the epidemiology of myasthenia gravis (MG) but a case ascertainment algorithm is lacking. We aimed to develop a valid algorithm for identifying MG patients in the older population with Medicare coverage. Local older patients (age ≥65) who received healthcare at the Cleveland Clinic and possessed Medicare coverage in 2014 and 2015 were selected. Potential MG patients were identified by using a combination of ICD9 or ICD10 codes for MG and MG-related text-word search. Diagnosis was categorized as "definite MG", "possible MG" or "non-MG" after review of clinical summaries by 5 neuromuscular specialists. Performances of various algorithms were tested by use of the definite MG cohort as a reference standard, and calculation of sensitivity, specificity, and predictive values. A total of 118 988 local older patients with Medicare coverage were identified. Usage of MG ICD codes and text-word search resulted in 125 patients with definite and 67 with possible MG. A total of 45 algorithms involving ICD usage, medication prescription, and specialty visit were tested. The best performing algorithm was identified as 2 office visits using MG ICD codes separated by at least 4 weeks or 1 hospital discharge and 1 office visit each using MG ICD codes separated by at least 4 weeks within the two-year period, resulting in a sensitivity and positive predictive value of 80% for identifying definite MG patients. Algorithms using ICD codes can reliably identify patients with MG with a high degree of accuracy.


Ventilation imaging with Kr-81m. A comparison with Xe-133.
Sixty-five patients with suspected pulmonary embolism were studied prospectively with both Kr-81m and Xe-133 ventilation imaging and Tc-99m MAA perfusion imaging. The krypton images, perfusion scintigrams and chest radiographs were read independently of the xenon images, perfusion scintigrams and chest radiographs by three observers. The studies of 53 patients were interpreted as normal or as indicative of a low or intermediate probability for pulmonary embolism with both gases. One study indicated intermediate probability with Xe-133 due to diffuse, severe xenon retention but low probability with Kr-81m because of close ventilation-perfusion correspondence. The studies of 9 patients indicated a high probability of embolism with both gases, while those of two additional patients (one with emboli at angiography) indicated a high probability only with Kr-81m. While essential agreement between Xe-133 and Kr-81m ventilation imaging was found in most patients, the significant difference in interpretation in 2 of 11 patients with probable pulmonary embolism suggests that a controlled, prospective trial with pulmonary angiography is warranted before Kr-81m is employed for routine clinical use.


NMDA receptors: linking physiological output to biophysical operation.
NMDA receptors are preeminent neurotransmitter-gated channels in the CNS, which respond to glutamate in a manner that integrates multiple external and internal cues. They belong to the ionotropic glutamate receptor family and fulfil unique and crucial roles in neuronal development and function. These roles depend on characteristic response kinetics, which reflect the operation of the receptors. Here, we review biologically salient features of the NMDA receptor signal and its mechanistic origins. Knowledge of distinctive NMDA receptor biophysical properties, their structural determinants and physiological roles is necessary to understand the physiological and neurotoxic actions of glutamate and to design effective therapeutics.


Effects of a week's beta-adrenoceptor blockade with atenolol and metoprolol CR/ZOK on the response to exercise in healthy women aged 50 to 70 years.
12 healthy women with a mean age of 60 years (range 50-70 years) were treated with 50 mg atenolol or 100 mg metoprolol CR/ZOK or placebo for 1 week in a double-blind, randomized, cross-over study. Laboratory measurements of the cardiovascular responses to exercise were made 2-4 hours after and again 24 hours after the last tablet. Blood pressure and heart rate at rest were reduced equally by the two beta-adrenoceptor antagonists. The reductions in blood pressure and heart rate during graded exercise and then during prolonged steady treadmill exercise 3-4 hours after the tablet were greater for atenolol than metoprolol CR/ZOK. The reductions in cardiac output showed a similar pattern. Lactate concentrations and ratings of perceived exertion tended to be highest on metoprolol CR/ZOK, but these differences were inconsistent. We conclude that despite the changes in the cardiovascular system in these 50-70 year-old women, exercise tolerance was not greatly affected by beta-adrenoceptor blockade.


Chromogenic and fluorogenic signaling of sulfite by selective deprotection of resorufin levulinate.
A new sulfite-selective probe system based on resorufin was investigated. Levulinate of resorufin exhibited a prominent chromogenic and turn-on type fluorogenic signaling toward sulfite ions in aqueous media based on the selective deprotection of the levulinate group. The sulfite-selective signaling was possible in the presence of commonly encountered anions.


One-Year Follow-Up of Vascular Intervention Trials Disrupted by the COVID-19 Pandemic: A Use-Case landscape.
The COVID-19 pandemic had an unprecedented impact on cardiovascular clinical research. The decision-making and state of study operations in cardiovascular trials 1-year after interruption has not been previously described. In the spring of 2020, we created a pandemic impact task force to develop a landscape of use case scenarios from 17 device trials of peripheral artery disease (PAD) and coronary artery disease (CAD) interventions. In conjunction with publicly available (clinictrials.gov) study inclusion criteria, primary endpoints and study design, information was shared for this use-case landscape by trial leadership and data owners. A total of 17 actively enrolling trials (9 CAD and 8 PAD) volunteered to populate the use case landscape. All 17 were multicenter studies (12 in North America and 5 international). Fifteen studies were industry-sponsored, of which 13 were FDA approved IDEs, one was PCORI-sponsored and two were sponsored by the NIH. Enrollment targets ranged from 150 to 9000 pts. At the time of interruption, 5 trials were <20 % enrolled, 9 trials were 50-80 % enrolled and 3 trials were >80 % enrolled. At 1 year, the majority of studies were continuing to enroll in the context of more sporadic but ongoing pandemic activity. At 1 year from the first surge interruptions, most trials had resumed enrollment. Trials most heavily interrupted were trials early in enrollment and those trials not able to pivot to virtual patient and site visits. Further work is needed to determine the overall impact on vascular intervention trials disrupted during the COVID-19 pandemic.


Counting-loss correction method based on window pulse shaping.
In order to obtain a precise X-ray counting rate, a window shaping algorithm is proposed and is applied. The proposed algorithm shapes original pulses into window pulses with sharp edge and stable width. In the experiment, the measured counting rate at 3.9uA tube current is used to estimate the incoming counting rate. The dead time and corrected counting rate are estimated by the paralyzable dead-time model. The experimental results show that the mean dead time of radiation events is 260ns and the relative mean deviation is 3.44% in the newly designed counting system. While the incoming counting rate is in the range of 100kcps to 2Mcps, the relative error of the corrected counting rate compared with the incoming counting rate is less than 1.78%. The proposed algorithm suppresses the dead time swing and improves the accuracy of the total counting rate of X-ray fluorescence spectrum.


The effect of temperature on the basal metabolism of cardiac muscle.
Using independent methods, measurements were made of the rate of oxygen consumption of quiescent rat ventricular tissue slices and of K+-arrested rabbit hearts at different temperatures. Experiments were designed such that the effect of temperature could be separated from the effect of time. The rate of oxygen consumption of both cardiac muscle preparations declined with time following cardiectomy. Likewise the rate of resting oxygen consumption of both preparations was relatively insensitive to temperature: Q10 = 1.3. By contrast, the rate of oxygen consumption of rat liver slices showed a Q10 of 2.6. The low Q10 values of the cardiac preparations do not appear to be due to an inadequate supply of oxygen. The results are in close agreement with those of myothermic studies.


Pulsar kicks via spin-1 color superconductivity.
We propose a new neutrino propulsion mechanism for neutron stars which can lead to strong velocity kicks, needed to explain the observed bimodal velocity distribution of pulsars. The spatial asymmetry in the neutrino emission is naturally provided by a stellar core containing spin-1 color-superconducting quark matter in the A phase. The neutrino propulsion mechanism switches on when the stellar core temperature drops below the transition temperature of this phase.


Perceptual constancy during ocular pursuit: a quantitative estimation procedure.
Perceptual constancy of visual motion is usually described as the degree of correspondence between physical and perceived characteristics of motion in the external world. To study it, one has to assess the relationship between physical motion, its retinal image, and its perception. We describe a quantitative estimation procedure for a measure K denoting the degree of perceptual constancy of background target motions noncollinear to the eye movements during ocular pursuit. The calculation of K is based on three vectors describing the target motion (1) as it is physically, (2) as it is mapped to the retina, and (3) as it is perceived, but only the direction of the perceptual motion vector has to be determined experimentally. K allows for quantitative comparison between experiments with a variety of parameters in visual motion displays.


Anesthesia for deep brain stimulation system implantation: adapted protocol for awake and asleep surgery using microelectrode recordings.
Deep brain stimulation (DBS), an effective treatment for movement disorders, usually involves lead implantation while the patient is awake and sedated. Recently, there has been interest in performing the procedure under general anesthesia (asleep). This report of a consecutive cohort of DBS patients describes anesthesia protocols for both awake and asleep procedures. Consecutive patients with Parkinson's disease received subthalamic nucleus (STN) implants either moderately sedated or while intubated, using propofol and remifentanil. Microelectrode recordings were performed with up to five trajectories after discontinuing sedation in the awake group, or reducing sedation in the asleep group. Clinical outcome was compared between groups with the UPDRS III. The awake group (n = 17) received 3.5 mg/kg/h propofol and 11.6 μg/kg/h remifentanil. During recording, all anesthesia was stopped. The asleep group (n = 63) initially received 6.9 mg/kg/h propofol and 31.3 μg/kg/h remifentanil. During recording, this was reduced to 3.1 mg/kg/h propofol and 10.8 μg/kg/h remifentanil. Without parkinsonian medications or stimulation, 3-month UPDRS III ratings (ns = 16 and 52) were 40.8 in the awake group and 41.4 in the asleep group. Without medications but with stimulation turned on, ratings improved to 26.5 in the awake group and 26.3 in the asleep group. With both medications and stimulation, ratings improved further to 17.6 in the awake group and 15.3 in the asleep group. All within-group improvements from the off/off condition were statistically significant (all ps < 0.01). The degree of improvement with stimulation, with or without medications, was not significantly different in the awake vs. asleep groups (ps > 0.05). The above anesthesia protocols make possible an asleep implant procedure that can incorporate sufficient microelectrode recording. Together, this may increase patient comfort and improve clinical outcomes.


Remote System for Daily Symptom Monitoring During Systemic Anticancer Treatment: Patient Acceptance, Usability, and Compliance.
Electronic systems for remotely monitoring symptoms during cancer treatment are increasingly being used. Most of them are intended for weekly or periodic symptom monitoring. The aim of this study was to explore the feasibility and usability of a remote system for daily symptom monitoring during systemic anticancer treatment. We offered a remote system for daily symptom monitoring to patients starting their first ever systemic therapy. Patient acceptance was observed as the proportion of patients showing interest in using the system. System users were invited to complete the "Health information Technology Usability Evaluation Scale," and the number of patients' self-reports was used to evaluate patient compliance. Of 465 patients, 239 (51.4%) showed interest in using the system; 111 system users reported a fairly good overall usability score (4 of 5), and perceived ease of use scored the highest (4.7 of 5) and perceived usefulness lowest (3.7 of 5). Their daily compliance was 68.8% (±31.1) at 3 weeks and 59.1% (±31.2) at 12 weeks after the start of treatment. Less than half of respondents (49.5%) and only one third (31.2%) perceived that their symptom reports were used by the nurses and doctors, respectively. Half of patients starting their first ever systemic treatment showed interest in using a remote system for daily symptom monitoring. For these patients, daily symptom monitoring seems acceptable, and the system is well complied within the first 12 weeks of treatment. A remote system for daily symptom monitoring is feasible and enables quick response to deteriorating symptoms. Use by healthcare professionals is a point of improvement.


Predictive Models for Kidney Recovery and Death in Patients Continuing Dialysis as Outpatients after Starting in Hospital.
For patients who initiate dialysis during a hospital admission and continue to require dialysis after discharge, outpatient dialysis management could be improved by better understanding the future likelihood of recovery to dialysis independence and the competing risk of death. We derived and validated linked models to predict the subsequent recovery to dialysis independence and death within 1 year of hospital discharge using a population-based cohort of 7657 patients in Ontario, Canada. Predictive variables included age, comorbidities, length of hospital admission, intensive care status, discharge disposition, and prehospital admission eGFR and random urine albumin-to-creatinine ratio. Models were externally validated in 1503 contemporaneous patients from Alberta, Canada. Both models were created using proportional hazards survival analysis, with the "Recovery Model" using Fine-Gray methods. Probabilities generated from both models were used to develop 16 distinct "Recovery and Death in Outpatients" (ReDO) risk groups. ReDO risk groups in the derivation group had significantly distinct 1-year probabilities for recovery to dialysis independence (first quartile: 10% [95% confidence interval (CI), 9% to 11%]; fourth quartile: 73% [70% to 77%]) and for death (first quartile: 12% [11% to 13%]; fourth quartile: 46% [43% to 50%]). In the validation group, model discrimination was modest (c-statistics [95% CI] for recovery and for death quartiles were 0.70 [0.67 to 0.73] and 0.66 [0.62 to 0.69], respectively), but calibration was excellent (integrated calibration index [95% CI] was 7% [5% to 9%] and 4% [2% to 6%] for recovery and death, respectively). The ReDO models generated accurate expected probabilities of recovery to dialysis independence and death in patients who continued outpatient dialysis after initiating dialysis in hospital. An online tool on the basis of the models is available at https://qxmd.com/calculate/calculator_874 .


The total value of time of children undergoing treatment: A contingent valuation from the perspective of parents in the orthopaedic department of a Dutch hospital.
Children spend substantial amounts of time receiving medical care (patients' time), and this patients' time plays an important role in parental choices for paediatric care. However, it is usually ignored in economic evaluations. This is a concern because economic evaluations are increasingly being used to inform child health policy decision-making. This study aims to quantify the time children spend receiving medical care and attach a monetary value to it for use in economic evaluations. It applied the parents' perspective. Consequently, the derived money values are the time values for both child and the accompanying parent. We used the contingent valuation methodology. We collected data on 83 children undergoing orthopaedic treatment in a Dutch hospital. Accompanying parents were asked to quantify and value the patients' time of their children. We separately explored travel, waiting and treatment time. We also checked whether the monetary valuation varied across parents' financial situation, children's health and level of pain. Parents were willing to pay about €33 (confidence interval (CI) 21.2-48.1) for a 1-day reduction in treatment time; about €11.5 (CI 4.2-19.1) for an hour's reduction in waiting time; and about €4.5 (CI 1.5-7.4) for an hour's reduction in travel time. In addition, respondents with better financial conditions have, on average higher, willingness to pays. To our knowledge, this is the first instance that patients' time of children has been monetarily valued. This methodology can be used to further develop economic evaluations of paediatric care and could be applied to larger samples with varying clinical conditions.


The quality evolution in managed care organizations: shifting the focus to community health.
Community demand for high-quality, cost-effective health care is forcing many new changes for managed care organizations (MCOs). Competition among MCOs often prevents cooperative and comprehensive approaches to the enhancement of the health status of the community. MCOs are beginning to measure quality based on the health of enrolled populations, and communities are seeking communitywide quality of care indicators. To cope with the demands of capitated health care, MCOs need to shift their focus to managing the health status of specific community populations. Strategies for managing the health status of populations include community assessments, collaboration among competing players, and a focus on consumer health information.


MALT lymphoma: Genetic abnormalities, immunological stimulation and molecular mechanism.
Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) occurs at diverse anatomic sites and is closely associated with several distinct chronic inflammatory disorders. Both the acquired genetic abnormalities and active chronic immunological responses play a critical role in the development of MALT lymphoma, interestingly by dysregulating similar molecular mechanisms. The three translocations seen in MALT lymphoma, namely t(14;18)(q32;q21)/IGH-MALT1, t(1;14)(p22;q32)/BCL10-IGH, and t(11;18)(q21;q21)/BIRC3 (API2)-MALT1 are capable of activating both canonical and non-canonical NF-κB pathways. TNFAIP3 (A20) inactivation by deletion and/or mutation abolishes its negative regulation to several signalling including BCR and TLR, which activate the canonical NF-κB pathway. Similarly, the immunological responses also activate the canonical NF-κB pathway via surface antigen receptor and TLR, and the non-canonical NF-κB pathway by T-cell help and BAFFR. There is also emerging evidence indicating oncogenic cooperation between the above genetic changes and immunological stimulation in the pathogenesis of MALT lymphoma.


Anatomical variations of the semilunar notch in elbow dislocations.
The anatomical relations of the semilunar notch of the ulna were studied in radiographs, taken in a strict lateral view, from 100 patients with elbow dislocations. The results were compared with those from a control group of 150 patients without dislocation or other radiographic pathology. We found that the coronoid process and an angle (a) formed between the axis of the ulna and a line going through the tip of the coronoid process and the tip of the olecranon were significantly smaller than those in the control group (P = 0.02). The central angle of the semilunar notch was significantly larger in the dislocation group than in the control group (P = 0.009). The smaller angle (a) and larger central angle in the dislocation group are a result of a lower coronoid process, but they are also due to the prominent tip of the olecranon. The results suggest that the dislocation mechanism is partly a hyperextension, with the tip of the olecranon as the pivot point.


Lidocaine has a narrow antiarrhythmic dose range against ventricular arrhythmias induced by programmed electrical stimulation in conscious postinfarction dogs.
The aim of the present study was to investigate the dose-dependent antiarrhythmic efficacy of lidocaine against electrically induced tachycardias in conscious, chronically instrumented postinfarction dogs. Programmed electrical stimulation (PES) was performed in 16 dogs 8 to 21 days after a 4 h occlusion of the left anterior descending coronary artery (LAD). Infusion of saline in 8 control animals with sustained ventricular tachycardia (SVT) inducible at baseline did not affect subsequent inducibility. In the treatment group 7 of 8 animals responded with SVT and one exhibited ventricular fibrillation at baseline. After an initial bolus of 1 mg/kg lidocaine intravenously (i.v.), the drug was infused at infusion rates of 40, 80 and 120 micrograms/kg/min (i.v.). During 80 micrograms/kg/min lidocaine (mean plasma level 3.5 micrograms/ml) 7 out of 8 animals displayed an antiarrhythmic response; both the lower and the higher infusion rate were associated with a smaller antiarrhythmic efficacy (3 of 8 animals responded to 40 micrograms/kg/min and 4 of 8 to 120 micrograms/kg/min). Licocaine did not affect ventricular refractory periods, but induced an increase in intraventricular conduction time at all infusion rates, from 66.2 ms at baseline to 67.7 ms (p less than 0.05), 67.7 ms (p less than 0.05), 70.0 ms (p less than 0.01) respectively. In conclusion the present study demonstrates that lidocaine is of considerable value in the management of PES-induced ventricular arrhythmias in the postinfarction phase. However there is only a small optimal therapeutic plasma level range, where lidocaine exhibits its antiarrhythmic efficacy against this type of arrhythmia; this makes a carefully titration of the drug necessary both in the experimental and in the clinical setting.


Sacral anterior root stimulation: prerequisites and indications.
An intact sacral reflex arc, or at least an intact second motor-neuron and a detrusor being able to contract, are the two prerequisites for implanting an anterior sacral root stimulator. Transrectal electrostimulation or direct needle stimulation of the sacral roots may reveal if patients despite absent or only weak detrusor contractions on routine investigation are suitable. Patients with a complete midthoracic paraplegia are the ideal candidates, but tetraplegics also benefit. Patients with incomplete lesions and preserved pain sensations are suitable provided that they can undergo posterior sacral root rhizotomy. Non-traumatic spinal cord lesions follow the same rules, provided that the type of lesion does not allow recovery and is not progressive. Myelomeningocele patients may be suitable provided that the pathoanatomy of the sacral roots permits the operation (may be possible only in thoracolumbar myelomeningocele). Vesico-uretero-renal reflux is no contraindication; it may even be a strong indication, if a low compliance bladder or high detrusor contractions are the main reasons for it. In most patients the procedure should or must be combined with posterior sacral root rhizotomy in order to normalize a low compliance, to abolish spontaneous reflex contractions, and to achieve continence. The benefit of following these rules is reflected in our own series of 30 patients. In all of them the operation has improved considerably the quality of life and no patient so far has regretted the operation.


Modulation of plant acetyl-CoA synthetase activity by post-translational lysine acetylation.
Acetyl-CoA synthetase (ACS) is one of several enzymes that generate the key metabolic intermediate, acetyl-CoA. In microbes and mammals ACS activity is regulated by the post-translational acetylation of a key lysine residue. ACS in plant cells is part of a two-enzyme system that maintains acetate homeostasis, but its post-translational regulation is unknown. This study demonstrates that the plant ACS activity can be regulated by the acetylation of a specific lysine residue that is positioned in a homologous position as the microbial and mammalian ACS sequences that regulates ACS activity, occurring in the middle of a conserved motif, near the carboxyl-end of the protein. The inhibitory effect of the acetylation of residue Lys-622 of the Arabidopsis ACS was demonstrated by site-directed mutagenesis of this residue, including its genetic substitution with the non-canonical N-ε-acetyl-lysine residue. This latter modification lowered the catalytic efficiency of the enzyme by a factor of more than 500-fold. Michaelis-Menten kinetic analysis of the mutant enzyme indicates that this acetylation affects the first half-reaction of the ACS catalyzed reaction, namely, the formation of the acetyl adenylate enzyme intermediate. The post-translational acetylation of the plant ACS could affect acetate flux in the plastids and overall acetate homeostasis.


Half-sib mating structures.
All ways in which all matings in a population can be between half-sibs under a generalization of regular systems of inbreeding are characterized for both finite and infinite populations. A model of random half-sib mating is developed and analyzed, and the asymptotic configuration of populations subject to it is described. The classical model of half-sib mating which ensues from the standard definition of regular systems of inbreeding is only one of many ways a population can propagate by half-sib mating, and a wide range of genetic identity is possible dependent on which half-sib mating structure governs a population.


Sympathetic nervous system activity is associated with choroidal thickness and axial length in school-aged children.
We aim to explore the effect of sympathetic nervous system (SNS) on choroid thickness (ChT) and axial length (AL). Students of grade 2 and 3 from a primary school were included and followed for 1 year. Visual acuity, refraction, AL and ChT were measured. Morning urine samples were collected for determining SNS activity by analysing concentrations of epinephrine, norepinephrine and dopamine using the liquid chromatography-tandem mass spectrometry. The most important factor (factor 1) was calculated using factor analysis to comprehensively indicate the SNS activity. A total of 273 students were included, with an average age of 7.77±0.69 years, and 150 (54.95%) were boys. Every 1 µg/L increase in epinephrine is associated with 1.60 µm (95% CI 0.30 to 2.90, p=0.02) decrease in average ChT. Every 1 µg/L increase in norepinephrine is associated with 0.53 µm (95% CI 0.08 to 0.98, p=0.02) decrease in the ChT in inner-superior region. The factor 1 was negatively correlated with the ChT in the superior regions. Every 1 µg/L increase in norepinephrine was associated with 0.002 mm (95% CI 0.0004 to 0.004, p=0.016) quicker AL elongation. The factor 1 was positively correlated with AL elongation (coefficient=0.037, 95% CI 0.005 to 0.070, p=0.023). We hypothesised that chronic stress characterised by elevated level of the SNS, was associated with significant increase in AL elongation, probably through thinning of the choroid.


Distribution of locoweed toxin swainsonine in populations of Oxytropis lambertii.
Oxytropis lambertii has been considered to be one of the major locoweeds responsible for livestock poisoning on rangelands, but there has been much confusion as to its taxonomic identity. The objective of this study was to conduct a field survey of several populations of each of the three varieties [var. lambertii Pursh; var higelovii A. Gray; var. articulata (E. Greene) Barneby] to document the presence or absence of the locoweed toxin, swainsonine. Swainsonine was found at detectable levels (>0.001% dry weight) in only five populations of var. higelovii in the southwest portion of its distribution in southern Utah, Arizona, and southwestern New Mexico, USA. No swainsonine was detected in populations in the northeast areas of its distribution (eastern Utah, Colorado, northeastern New Mexico, USA). The other varieties, articulata and lambertii, also did not contain swainsonine. It is suspected that a plant fungal endophyte may be responsible for the high variability in swainsonine content in populations of O. lambertii.


Characterization of Elastofibroma Dorsi with (18)FDG PET/CT: a retrospective study.
Elastofibroma dorsi has been described in the literature as an unusual tumor or pseudotumor. However, autopsies and imaging studies have revealed that it is a non-negligible finding. The aim of this study has been to illustrate and become familiar with this type of lesion in order to prevent misdiagnosis. From 3 December 2008 to 5 January 2010, 1,751 patients were evaluated with (18)FDG-PET/CT. Of these, 29 cases of elastofibroma dorsi were recorded as an incidental finding. A retrospective and descriptive analysis was performed on this study series. The study showed a prevalence of 1.66%. Out of the 29 findings, 22 (75.86%) were females and 7 (24.14%) males. Seventeen (58.62%) cases were bilateral, 12 (41.38%) unilateral and the SUVmax ranged from 1.4 to 3.2. These lesions were reported as soft tissue density images with mild or moderate diffuse metabolic activity. The elastofibroma dorsi is a relatively common finding in PET/CT that should be known in order to avoid making wrong diagnoses.


R3 receptor tyrosine phosphatases: conserved regulators of receptor tyrosine kinase signaling and tubular organ development.
R3 receptor tyrosine phosphatases (RPTPs) are characterized by extracellular domains composed solely of long chains of fibronectin type III repeats, and by the presence of a single phosphatase domain. There are five proteins in mammals with this structure, two in Drosophila and one in Caenorhabditis elegans. R3 RPTPs are selective regulators of receptor tyrosine kinase (RTK) signaling, and a number of different RTKs have been shown to be direct targets for their phosphatase activities. Genetic studies in both invertebrate model systems and in mammals have shown that R3 RPTPs are essential for tubular organ development. They also have important functions during nervous system development. R3 RPTPs are likely to be tumor suppressors in a number of types of cancer.


Cystic fibrosis in neonates and infants.
Cystic fibrosis (CF) is a common autosomal recessive disorder, characterized by chronic bronchopulmonary infection, pancreatic insufficiency, and subsequently, other multisystem complications. Most children are diagnosed before school age. Here we review the pathophysiology of the condition, the age-related presentations of CF up until school age, and the appropriate use of diagnostic tests. A specialist centre should supervise treatment. There are exciting new advances in monitoring techniques in the preschool years, including CT scanning, bronchoscopy and gas mixing indices. Recent advances in the knowledge of the molecular biology of CF hold out the hope of specific therapies which can reverse the underlying defect causing death from CF lung disease.


What is the risk of prostate cancer mortality following negative systematic TRUS-guided biopsies? A systematic review.
To investigate the risk of prostate cancer-specific mortality (PCSM) following initial negative systematic transrectal ultrasound-guided (TRUS) prostate biopsies. Systematic review. PubMed and Embase were searched using a string combination with keywords/Medical Subject Headings terms and free text in the search builder. Date of search was 13 April 2020. Studies addressing PCSM following initial negative TRUS biopsies. Randomised controlled trials and population-based studies including men with initial negative TRUS biopsies reported in English from 1990 until present were included. Data extraction was done using a predefined form by two authors independently and compared with confirm data; risk of bias was assessed using the Newcastle-Ottawa Scale for cohort studies when applicable. Four eligible studies were identified. Outcomes were reported differently in the studies as both cumulative incidence and Kaplan-Meier estimates have been used. Regardless of the study differences, all studies reported low estimated incidence of PCSM of 1.8%-5.2% in men with negative TRUS biopsies during the following 10-20 years. Main limitation in all studies was limited follow-up. Only a few studies have investigated the risk of PCSM following initial negative biopsies and all studies included patients before the era of MRI of the prostate. However, the studies point to the fact that the risk of PCSM is low following initial negative TRUS biopsies, and that the level of prostate-specific antigen before biopsies holds prognostic information. This may be considered when advising patients about the need for further diagnostic evaluation. CRD42019134548.


CreLite: An optogenetically controlled Cre/loxP system using red light.
Precise manipulation of gene expression with temporal and spatial control is essential for functional analysis and determining cell lineage relationships in complex biological systems. The cyclic recombinase (Cre)-loxP system is commonly used for gene manipulation at desired times and places. However, specificity is dependent on the availability of tissue- or cell-specific regulatory elements used in combination with Cre. Here, we present CreLite, an optogenetically controlled Cre system using red light in developing zebrafish embryos. Cre activity is disabled by splitting Cre and fusing with the Arabidopsis thaliana red light-inducible binding partners, PhyB and PIF6. Upon red light illumination, the PhyB-CreC and PIF6-CreN fusion proteins come together in the presence of the cofactor phycocyanobilin (PCB) to restore Cre activity. Red light exposure of zebrafish embryos harboring a Cre-dependent multicolor fluorescent protein reporter injected with CreLite mRNAs and PCB resulted in Cre activity as measured by the generation of multispectral cell labeling in several different tissues. Our data show that CreLite can be used for gene manipulations in whole embryos or small groups of cells at different developmental stages, and suggests CreLite may also be useful for temporal and spatial control of gene expression in cell culture, ex vivo organ culture, and other animal models.


Combined virtual screening, MMPBSA, molecular docking and dynamics studies against deadly anthrax: An in silico effort to inhibit Bacillus anthracis nucleoside hydrolase.
Anthrax is a deadly disease caused by Bacillus anthracis, a dangerous biological warfare agent employed for both military and terrorist purposes. A critical selective target for chemotherapy against this disease is nucleoside hydrolase (NH), an enzyme still not found in mammals. In the current study, we have performed molecular docking and dynamics studies, aiming to propose the new potent inhibitors of B. anthracis NH among National Cancer Institute (NCI) Diversity Set. We also analyzed the principal interactions of proposed compounds with the active site residues of NH and the relevant factors to biological activity. Additionally, the physic-chemical properties of free and inhibitor bound NH were evaluated and discussed. Our data showed that compound NSC79887 is a good candidate to inhibit NH and also for biological tests and further development. Also, ADMET prediction revealed that all physic-chemical parameters are within the acceptable range defined for human use.


Various impacts of driver mutations on the PD-L1 expression of NSCLC.
We aimed to evaluate whether different driver mutations have varying impacts on the programmed cell death-ligand 1 (PD-L1) expression of non-small cell lung cancer (NSCLC), and whether the prognostic roles of PD-L1 amongst our patients were divergent. This was a single-institute study that included patients with NSCLC. Six driver mutations, PD-L1 status, and the outcomes of treatment were assessed. A total of 1,001 NSCLC patients were included for analysis. Overall, the PD-L1 positive (TPS ≥ 1%) and strong positive (TPS ≥ 50%) rates were 52.2% and 17.3%, respectively. As compared with wild type lung adenocarcinoma, EGFR-mutant and HER2-mutant patients had similarly low PD-L1 and strong PD-L1 positive rates. BRAF-mutant patients had numerically higher PD-L1 and strong PD-L1 positive rates. Patients with fusion mutation (ALK and ROS1) (aOR 2.32 [95% CI 1.10-4.88], P = 0.027 and 2.33 [95% CI 1.11-4.89], P = 0.026), KRAS mutation (aOR 2.58 [95% CI 1.16-5.75], P = 0.020 and 2.44 [95% CI 1.11-5.35], P = 0.026), and non-adenocarcinoma histology (aOR 2.73 [95% CI 1.72-4.34], P < 0.001 and 1.93 [95% CI 1.13-3.30], P = 0.016) all had significantly higher PD-L1 and strong PD-L1 positive rates. A trend towards longer survival was noted in ROS-1 rearranged and KRAS-mutant patients with strong PD-L1 expression who had received crizotinib and chemotherapy, respectively. In conclusion, individual driver mutations had various impacts on the PD-L1 expression of NSCLC patients. The prognostic role of PD-L1 may also be divergent amongst patients harboring different driver mutations.


Transcriptional changes revealed water acidification leads to the immune response and ovary maturation delay in the Chinese mitten crab Eriocheir sinensis.
Nowadays, due to increasing carbon dioxide released, water acidification poses a series of serious impacts on aquatic organisms. To evaluate the effects of water acidification on crustaceans, we focused on the Chinese mitten crab Eriocheir sinensis, which is a spawning migration and farmed species in China. Based on histological and oocyte transparent liquid observation, we found that the acidified environment significantly delayed the ovarian maturation of E. sinensis. Moreover, RNA-seq was applied to obtain gene expression profile from the crab's gills and ovaries in response to acidified environment. Compared with control groups, a total of 5471 differentially expressed genes (DEGs) were identified in acidified gills and 485 DEGs were identified in acidified ovaries. Enrichment analysis indicated that some pathways also responded to the acidified environment, such as PI3K-Akt signaling pathway, Chemokine signaling pathway, apoptosis, and toll-like receptor signaling pathway. Subsequently, some DEGs involved in immune response (ALF, Cathepsin A, HSP70, HSP90, and catalase) and ovarian maturation (Cyclin B, Fem-1a, Fem-1b, and Fem-1c) were selected to further validate the influence of water acidification on gene expression by qRT-PCR. The results showed that the expression level of immune-related genes was significantly increased to response to the water acidification, while the ovarian maturation-related genes were significantly decreased. Overall, our data suggested that E. sinensis was sensitive to the reduced pH. This comparative transcriptome also provides valuable molecular information on the mechanisms of the crustaceans responding to acidified environment.


Anaerobic oxidation of methane with sulfate: on the reversibility of the reactions that are catalyzed by enzymes also involved in methanogenesis from CO2.
Anaerobic oxidation of methane (AOM) with sulfate is apparently catalyzed by an association of methanotrophic archaea (ANME) and sulfate-reducing bacteria. In many habitats, the free energy change (ΔG) available through this process is only -20 kJ/mol and therefore AOM with sulfate reduction generating life-supporting ATP is predicted to operate near thermodynamic equilibrium (ΔG=0 kJ/mol). On the basis of meta-genome sequencing and enzyme studies, it has been proposed that AOM in ANME is catalyzed by the same enzymes that catalyze CO2 reduction to CH4 in methanogenic archaea. Here, this proposal is reviewed and evaluated in terms of the process thermodynamics, kinetics, and enzyme reversibilities. Currently, there is no evidence for the presence of the gene that encodes methylene-tetrahydromethanopterin reductase in ANME, one of the central enzymes in the CO2 to CH4 pathway. However, all of the remaining enzymes do appear to be present and, with the exception of a coenzyme M-S-S-coenzyme B heterodisulfide reductase, all of these enzymes have been confirmed to catalyze reversible reactions.


Dulaglutide provides protection against sepsis-induced lung injury in mice by inhibiting inflammation and apoptosis.
Sepsis is a dangerous condition with a high mortality rate. In addition to promoting insulin secretion in a glucose-dependent manner, glucagon-like peptide-1 (GLP-1) also exhibits anti-inflammatory properties. Dulaglutide is a glucagon-like peptide-1 receptor agonist (GLP-1 RA). In this study, we investigated the effects and mechanism of action of dulaglutide (Dul) in lipopolysaccharide (LPS) induced lung injury in mice with sepsis. In mice with LPS (15 mg/kg, ip, qd)-induced acute lung injury, the administration of dulaglutide (0.6 mg/kg, ip, qd) improved weight loss, reduced lung injury, reversed the increase in IL-1β, TNF-α, IL-6, CXCL1, CCL2 and CXCL2 expression in the lung, and reduced the infiltration of neutrophils and macrophages in the lung tissues. The decline in caspase-3, cleaved caspase-3, caspase-8, and Bcl-2/Bax expression and the increase in the number of TUNEL positive cells in the lung were reversed, suggesting that GLP-1RA could play a protective role in the lung by inhibiting inflammation and apoptosis. In addition, GLP-1RA could reduce the expression of P-STAT3 and NLRP3, suggesting that P-STAT3 and NLRP3 may be potential targets against lung injury in sepsis. Collectively, our data demonstrated that GLP-1RA exerts a protective effect against sepsis-induced lung injury through mechanisms related to the inhibition of inflammation, apoptosis, and STAT3 signaling.


From research to policy: rural women in India.
The following article describes the new awareness of rural women's role in development in India that has resulted from studying rural women directly. It indicates the possibility of moving from research on rural women to the formation of policy and the design of programs that take into account the reality of rural women's lives.


Multiple cellular proteins modulate the dynamics of K-ras association with the plasma membrane.
Although specific proteins have been identified that regulate the membrane association and facilitate intracellular transport of prenylated Rho- and Rab-family proteins, it is not known whether cellular proteins fulfill similar roles for other prenylated species, such as Ras-family proteins. We used a previously described method to evaluate how several cellular proteins, previously identified as potential binding partners (but not effectors) of K-ras4B, influence the dynamics of K-ras association with the plasma membrane. Overexpression of either PDEδ or PRA1 enhances, whereas knockdown of either protein reduces, the rate of dissociation of K-ras from the plasma membrane. Inhibition of calmodulin likewise reduces the rate of K-ras dissociation from the plasma membrane, in this case in a manner specific for the activated form of K-ras. By contrast, galectin-3 specifically reduces the rate of plasma membrane dissociation of activated K-ras, an effect that is blocked by the K-ras antagonist farnesylthiosalicylic acid (salirasib). Multiple cellular proteins thus control the dynamics of membrane association and intercompartmental movement of K-ras to an important degree even under basal cellular conditions.


Noninvasive cardiac output monitoring during general anesthesia for Cesarean delivery in a patient with severe aortic stenosis.
The anesthetic management of women with severe aortic stenosis (AS) undergoing Cesarean delivery (CD) remains controversial. We used a relatively new bioreactance technology to highlight the continuous hemodynamic changes related to anesthesia, delivery, and recovery in a parturient with severe AS. A 29-yr-old woman, New York Heart Association Class II, with a congenital bicuspid aortic valve and AS presented for CD at 36.5 weeks of gestation. The estimated aortic valve area on echocardiogram was 0.75 cm(2), and the maximal transvalvular gradient was 64 mmHg. Cesarean delivery was performed under general anesthesia with an epidural catheter placed prior to induction for postoperative analgesia. Noninvasive cardiac output (CO) monitoring based on bioreactance was used throughout the procedure. Cardiac output increased from 7-12 L·min(-1) following delivery primarily due to an increase in stroke volume. Both stroke volume variation and total peripheral resistance decreased, while the patient's heart rate did not change. Increased stroke volume, likely associated with decreased afterload and increased preload, contributed to an increase in CO from 7-12 L·min(-1). Continuous CO data obtained from bioreactance-based monitoring suggests that pregnant women with severe AS may experience an increase in CO under certain circumstances. This result is in keeping with data obtained from non-pregnant individuals and is an interesting finding that warrants further study. Noninvasive CO monitoring may improve our understanding of the peripartum changes in women with heart disease.


Soft tissue sarcoma diagnosed subsequent to lymphoma is associated with prior radiotherapy and decreased survival.
Cancer survivors are at increased risk for second malignancies, and vigilance is thus required. The authors sought to determine whether there was an association among lymphoma, sarcoma, and the associated treatments for these diseases. From the authors' prospective soft tissue sarcoma (STS) database of 8240 patients, they identified 112 patients with STS and lymphoma treated from 1982 to 2009 who had complete follow-up data. They examined the importance of the initial diagnosis in patients with both STS and lymphoma, in addition to determining the role of radiation therapy, a known inducer of sarcoma. Review of their sarcoma, gastric, urology, breast, and gynecology databases revealed that lymphoma (95%) or leukemia (5%) occurred in 1.6% of STS patients in comparison to 0.5% of patients in the other databases (P < .01; odds ratio, 3.1; 95% confidence interval, 2.6-3.8). Patients diagnosed with STS only were more likely to die of disease at 10 years compared with those with STS and lymphoma (P = .006), but this difference was not significant when patients presenting with recurrence or metastases were excluded. Among patients with lymphoma and STS, lymphoma was the first diagnosis in 71% of patients. Median survival after STS diagnosis was shorter when lymphoma was the initial diagnosis (67 vs 170 months, P = .002), and these patients were more likely to have radiation-associated STS (44% vs 3%, P < .001). There was a 3-fold higher incidence of lymphoma in STS patients compared with other solid tumors. The poor prognosis of those diagnosed with both STS and lymphoma was most likely a consequence of prior irradiation.


Hemostatic abnormalities in HIV disease.
Hemostatic abnormalities are prominent and enigmatic features of HIV infection. In the foregoing discussion, many questions have been raised about the pathogenesis and treatment of HIV-related ITP, TTP, and ACA. The mechanism of platelet destruction in HIV-infected patients remains poorly defined, and the way in which HIV triggers these hemostatic abnormalities is unknown. Treatment of patients in the shadow of AIDS also poses unique problems for the clinician. Nevertheless, HIV-related thrombocytopenia provides a model for other forms of immune cytopenias, and better understanding of this form of ITP will lead to improved treatment modalities for other autoimmune diseases. Conversely, HIV-related ITP, TTP, and ACA should be viewed as part of a spectrum of autoimmune processes triggered by HIV. By defining the significance of these autoimmune processes in AIDS, more effective approaches to the treatment of HIV disease can and will be developed.


Whole-genome resequencing of large yellow croaker (Larimichthys crocea) reveals the population structure and signatures of environmental adaptation.
Large yellow croaker is an economically important fish in China and East Asia. Despite its economic importance, genome-wide adaptions of domesticated large yellow croaker are largely unknown. Here, we performed whole-genome resequencing of 198 individuals of large yellow croaker obtained in the sea or from farmers in Zhoushan or Ningde. Population genomics analyses revealed the genetic population structure of our samples, reflecting the living environment. Each effective population size is estimated to be declining over generations. Moreover, we identified genetically differentiated genomic regions between the sea-captured population in the Zhoushan Sea area and that of the Ningde Sea area or between the sea-captured population and the farmed population in either area. Gene ontology analyses revealed the gene groups under selective sweep for the adaptation to the domesticated environment. All these results suggest that individuals of the large yellow croaker populations show genomic signatures of adaptation to different living environments.


Glossopharyngeal and vagal afferent projections to the brain stem of the cat: a horseradish peroxidase study.
Brain stem projections of the glossopharyngeal and vagus nerves in the cat were studied using the anterograde transport of horseradish peroxidase (HRP). Crystalline HRP was applied to the proximal cut ends of the nerves for a period of 4-10.5 h, and after a survival time of 24-120 h, transverse and horizontal sections of the brain stem were processed according to the tetramethylbenzidine method. Labeled fibers from both nerves were found to project bilaterally to the solitary complex, and ipsilaterally to the ventral region of the external cuneate nucleus and to the medial region of the nucleus praepositus hypoglossi, just dorsolateral to the medial longitudinal fasciculus. Within the solitary complex terminal labeling was found in the parvocellular, ventrolateral, lateral, medial and commissural solitary nuclei. Exclusive glossopharyngeal nerve projections were found ipsilaterally in the rostral dorsal motor nucleus of the vagus, the ventrolateral portion of the medial cuneate nucleus, the dorsal part of the nuclei caudalis and interpolaris of the trigeminal complex, the nuclei insulae cuneati lateralis, and the dorsolateral aspect of the nucleus medullae oblongata centralis. Finally, in the area postrema a bilateral projection of vagal and an ipsilateral projection of glossopharyngeal fibers were found. These findings demonstrate that the glossopharyngeal nerve has more widely distributed brain stem projections that the vagus nerve and provide essential information on projection sites of visceral and taste inputs to the central nervous system.


Extraction of glycolytic enzymes: myo-inositol as a marker of membrane porosity.
Detergent extraction of brain slices and mouse fibroblast 3T3 cells was performed to determine rates and relative amounts of extraction of inositol versus the glycolytic enzymes. The two detergents, Triton X-100 and Brij 58, led to similar results for extraction of myo-inositol. The extraction of enzymes from brain slices or cells varied with the detergent. In brain slices, a buffered solution containing 0.2% of the detergent Brij 58 led to the extraction of 85% of the inositol before 3% of the aldolase or before 37% of either lactate dehydrogenase or triose phosphate isomerase was extracted. In contrast, with 0.1% Triton X-100 in isotonic phosphate-buffered saline, when 70% of the inositol was extracted, 33% of the aldolase and 48% of the triose phosphate isomerase were extracted. Lesser amounts of aldolase and glyceraldehyde phosphate dehydrogenase were extracted than most of the other glycolytic enzymes under all conditions, implying that these enzymes may be interacting with non-extractable subcellular components. In 3T3 cells, both detergents were of similar effectiveness for inositol extraction. Triton X-100 caused 89% of the inositol to be released and Brij 58 caused 84% to be released. With the enzymes, Brij 58 caused between 15 and 38% extraction and Triton X-100 caused between 61 and 85% extraction of the different glycolytic enzymes. Thus Brij 58 was as effective as Triton X-100 in inositol extraction but not nearly as effective in glycolytic enzyme extraction. The results demonstrate that inositol leakage from tissues or cells is a better indicator of detergent-mediated alterations in membrane porosity than glycolytic enzyme leakage.(ABSTRACT TRUNCATED AT 250 WORDS)


Updated Treatment for Acne: Targeted Therapy Based on Pathogenesis.
Previous approaches to acne management have focused on the four main factors implicated in acne, namely, androgen-mediated sebogenesis (considered integral to acne), hyperkeratinization, colonization with Cutibacterium acnes, and inflammation related to both innate and adaptive mechanisms. Recent advances have facilitated potential novel approaches to acne management, as the pathophysiology and the immunological aspects related to acne and wound healing have evolved. Particular targets that have been shown to be closely involved in acne pathophysiology and wound healing include interleukin (IL)-1β, IL-17, IL-23, and tumor necrosis factor alpha (TNFα). Biological antibodies targeting IL-1β, IL-17, IL-23, and TNFα could provide novel approaches for treating severe acne and related disorders. Acne is primarily a disease associated with sebogenesis. Monosaturated free acids are important components. Insulin growth factor 1 (IGF-1) promotes the proliferation and differentiation of sebocytes and IL-1β. Research into the microbiome may also provide insights into potential future therapeutic options for acne. Scars, both atrophic and hypertrophic, are common sequelae to acne. Risk factors associated with the development of acne scars include genetic, systemic, local, and lifestyle factors. Pro-inflammatory cytokines have been shown to play a crucial role in the development of acne-induced hypertrophic scars. Treatment for extensive inflammatory keloid scarring is limited. Surgery and postoperative radiotherapy are two possible options. Transforming growth factor-β (TGFβ), IL-6, matrix metalloproteinase (MMP), IGF-1, and B cells are found in keloid or hypertrophic scar tissues. Biological antibodies targeting these cytokines may be a potential strategy for the prevention and treatment of this type of scar in the future. Future treatment for acne should embrace approaches that target the main etiological factors of acne. In particular, specific emphasis on aggressive treatment in the acute inflammatory phase to reduce the likelihood of scarring and other clinical sequelae, such as pigmentary changes would be highly desirable. Treatment for established acne-induced sequelae should also be considered.


Hormonal regulation of liver phosphoenolpyruvate carboxykinase and glucokinase gene expression at weaning in the rat.
During the suckling period, the rats are fed continuously with milk, which is a high-fat low-carbohydrate diet (HF). At weaning, milk is progressively replaced by the rat's laboratory chow which is a high-carbohydrate low-fat diet (HCHO), and this is accompanied by large hormonal modifications: an increase in plasma insulin and a decrease in plasma glucagon concentrations, and by marked changes in metabolic pathways in liver: decrease in hepatic gluconeogenesis and increase in glycolysis and lipogenesis. Most of the data concerning these changes are related to maximal activity of enzymes. The recent availability of specific cDNA probes for phosphoenolpyruvate carboxykinase (PEPCK), and glucokinase (GK) has allowed the study of the role of pancreatic hormones and nutrition in the changes of the expression of these genes at weaning in the rat. Regarding phosphoenolpyruvate carboxykinase gene transcription, the concentration of mRNA as well as the activity of PEPCK are elevated in the liver of suckling rat until the onset of weaning, 21 d after delivery. After weaning to a HCHO diet, both mRNA and activity of PEPCK rapidly decrease to a very low level. In contrast, weaning on an HF diet, which maintains high plasma glucagon and low plasma insulin levels, does not decrease in plasma glucagon concentration and a 90% decrease in PEPCK gene transcription and PEPCK mRNA concentration in 1 h. Regarding glucokinase gene transcription, the concentration of mRNA as well as the activity of GK are not detectable before 15 d after birth in the liver of the rat. They markedly increase when the newborn are weaned on an HCHO diet but not when they are weaned on an HF diet.(ABSTRACT TRUNCATED AT 250 WORDS)


[Resource use and financing of guideline-adherent psychotherapeutic inpatient care].
The financing of psychiatric psychotherapeutic care in Germany is determined by the German psychiatric staffing regulations which are unchanged since 1991. Psychotherapy was established after 1991 as an effective and indispensable treatment of mental and behavioral disorders. The aim of this study was to empirically investigate the use of psychiatrists' and psychologists' working time for psychotherapy in guideline-adherent hospital care. A further aim was to compare these results to the resources defined by the German psychiatric staffing regulations and in the new prospective payment system for psychiatry and psychosomatics in Germany. University hospitals for psychiatry and psychotherapy were asked to retrospectively provide data of patients for which guideline-adherent care was possible. Participating institutions provided both data describing the staff time utilization of psychotherapeutic services provided by psychiatrists and psychologists and patient classifications according to the German psychiatric staffing regulations and the new prospective payment system for psychiatry and psychosomatics. Resources defined by the German psychiatric staffing regulations covered a mean of only 71 min of psychotherapy per patient and week while the actual mean intensity of psychotherapeutic care provided by the participating hospitals was 194 min per patient and week. The associated use of staff time was 102 min per patient and week. Both figures increased during an inpatient episode. The resources defined by the German psychiatric staffing regulations covered only 70 % of medical and psychological personnel. The current configuration of the new prospective payment system for psychiatry and psychosomatics covered only 59 % of staff time. The results of this study provide another unambiguous recommendation to adjust the out-dated German psychiatric staffing regulations to the current evidence and S3 guidelines for psychiatric psychotherapeutic hospital care. In particular, more resources are required for the provision of psychotherapeutic care.


Nonalcoholic fatty liver disease and risk of intracerebral hemorrhage.
This study aimed to investigate the association between the steatosis severity of nonalcoholic fatty liver disease (NAFLD) and future intracerebral hemorrhage (ICH) risk. We used data from the Kailuan study. Participants without a history of stroke, myocardial infarction, cancer, other liver diseases or alcohol abuse were enrolled. NAFLD and the severity of liver steatosis were assessed by abdominal ultrasonography. We stratified the participants into different groups according to the severity changes in liver steatosis status across the first 4-year follow-up period. The outcome was the first occurrence of ICH during the next 6-year follow-up period. Hazard ratios (HRs) and 95% CI of ICH were estimated using Cox models adjusted for potential risk factors. A total of 49,906 participants were enrolled in this study. During a median of 6.79 years of follow-up, 193 incident ICH cases were identified. Compared with persistent nonfatty liver participants, the hazard ratios (HRs) for participants with persistent mild steatosis, persistent moderate steatosis, persistent severe steatosis, alleviating steatosis, and aggravating steatosis were 1.28 (95% CI, 0.75-2.18), 2.33 (95% CI, 1.24-4.38), 1.63 (95% CI, 0.22-12.11), 1.41 (95% CI, 0.91-2.18), and 1.37 (95% CI, 0.94-2.00), respectively, in the fully adjusted model. NAFLD with persistent moderate steatosis was significantly related to an increased risk of future ICH, independent of other conventional risk factors.


Effects of prolonged inflation on pulmonary stretch receptor discharge in turtles.
The tonic and phasic discharge characteristics of single, slowly adapting pulmonary stretch receptors (SAR) were examined before and after 1 h periods of constant pressure inflation to normal resting (VLr, pressure = 0 cm H2O) and elevated (VLe, pressure = 10 cm H2O) lung volumes in turtles (Chrysemys sp.). Based on their discharge at VLr, SAR were classified as either low (n = 13) or high threshold (n = 4) receptors. Inflations were performed with both air and 5% CO2 in air. Lung gas composition and arterial PCO2 and pH were measured during the maintained inflations. In animals ventilated with air, low and high threshold receptors adapted by 57 and 30% respectively over the first 3 min at VLe. During the remainder of the 1 h period, the discharge of low threshold SAR fell an additional 20% while that of the high threshold SAR remained relatively constant. There were significant increases in both alveolar and arterial PCO2 during the maintained inflations. Ventilation with 5% CO2 reduced the static discharge levels of low and high threshold SAR by 10 and 25% respectively, suggesting that a part of the apparent adaptation of these receptors to maintained inflation for 1 h with air was due to the accumulation of metabolic CO2. Following 1 h of maintained inflation, the phasic responses to pump ventilation were decreased in low threshold SAR but remained unchanged in high threshold SAR. The static discharge associated with step inflation was unchanged in both receptor groups. The data suggest that increased SAR discharge is sustained indefinitely during increased lung volume and may account for persistent changes in breathing pattern previously observed during chronic changes in lung volume.


Experimental diabetic nephropathy is accelerated in matrix metalloproteinase-2 knockout mice.
Matrix metalloproteinase-2 (MMP-2) is responsible for the degradation of various types of extracellular matrix (ECM) proteins such as type IV collagen. Decreased MMP-2 expression and activity has been generally thought to contribute to increased accumulation of ECM at the advanced stage of diabetic nephropathy. However, the kinetics and role of MMP-2 in the early phase of diabetic nephropathy remain unclear. To address this issue, we examined whether streptozotocin (STZ)-induced early diabetic nephropathy was accelerated in MMP-2 knockout (KO) mice. Diabetes was induced by the injection of STZ in 6-week-old control and MMP-2 KO mice. Animals were killed after 16 weeks of diabetes of after observation alone. Compared with non-diabetic control mice, renal MMP-2 expression and activity were increased in 16-week old diabetic mice. Serum levels of blood urea nitrogen and creatinine and urinary excretion levels of albumin and N-acetyl-β-D-glucosaminidase were significantly elevated in diabetic MMP-2 KO mice when compared with wild-type diabetic littermates. Further, accumulation of ECM in the glomeruli and atrophy and fibrosis in the tubulointerstitium were exacerbated, and renal α-smooth muscle actin expression was enhanced in diabetic MMP-2 KO mice. Our present study suggests that renal expression and activity of MMP-2 are increased as a compensatory mechanism in the early phase of diabetic nephropathy. Since MMP-2 could play a protective role against the progression of diabetic nephropathy, further enhancement of MMP-2 expression and/or activity in the kidney may be a therapeutic target for the treatment of early diabetic nephropathy.


The impact of symptoms on daily life as perceived by patients with Charcot-Marie-Tooth type 1A disease.
In Charcot-Marie-Tooth type 1A (CMT1A) patients, daily life is mainly influenced by mobility and ambulation dysfunctions. The aim of our work was to evaluate the perception of disturbances that mostly impact on daily life in CMT1A patients and its difference on the basis of age, gender, disability, and quality of life. Forty-one CMT1A patients underwent neurological assessment focused on establishing clinical disability through the Charcot-Marie-Tooth Neuropathy Score (CMTNS) and quality of life through the Short Form-36 (SF-36) questionnaire. We identified from CMT disturbances 5 categories [weakness in lower limbs (WLL), weakness in upper limbs (WUL), skeletal deformities (SD), sensory symptoms (SS), balance (B)] and patients classified the categories from the highest to the lowest impact on daily life (1: highest; 5: lowest). Ranking of the 5 categories, in the overall sample and in the different subgroups (dividing by gender, median of age and disease duration, CMTNS, domains of SF-36), was obtained and differences among subgroups were assessed using a bootstrap approach. Rank analysis showed that WLL was the most important disturbance on daily life whereas WUL had the lowest impact. In the older CMT1A group, the most important disturbance on daily life was B that was also the most relevant disturbance in patients with a greater disability. SD influenced daily life in younger patients. SS had less impact on daily life, with the exception of patients with a milder disability. Our findings demonstrated that the perception of disturbances that mostly impact on CMT1A patients' daily life changes over the lifetime and with degree of disability.


Adduct formation at C-8 of guanine on in vitro reaction of the ultimate form of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine with 2'-deoxyguanosine and its phosphate esters.
We examined the reactivity of the N-hydroxyamino derivative of a carcinogenic heterocyclic amine, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), after its O-acetylation with four 2'-deoxyribonucleoside 3'-monophosphates. 32P-Postlabeling analysis demonstrated that the levels of adducts with 2'-deoxyguanosine 3'-monophosphate were much higher than those with the other three nucleotides. 1H-NMR, mass spectral and UV absorption spectral analyses of the major adducts formed by N-acetyoxy-PhIP with 2'-deoxyguanosine and with its phosphate esters indicated that PhIP bound at the C-8 position of guanine, as previously demonstrated with other heterocyclic amines.


[Cytological structures similar to those of steroid-producing glands in the mandibulary and Y glands of the crab Carcinus maenas L., whether normal or without eyestalk].
Mandibular glands and Y organs have characteristic organelles of steroid glands: a network of smooth endoplasmic reticulum and numerous mitochondria with tubular cristae. Development of S.E.R. and activation of mitochondria are stimulated in mandibular glands by eyestalk ablation.


Practical Synthesis of Phosphinic Amides/Phosphoramidates through Catalytic Oxidative Coupling of Amines and P(O)-H Compounds.
Herein, we report a highly efficient ZnI2 -triggered oxidative cross-coupling reaction of P(O)-H compounds and amines. This operationally simple protocol provides unprecedented generic access to phosphinic amides/phosphoramidate derivatives in good yields and short reaction time. Besides, the reaction proceeds under mild conditions, which avoids the use of hazardous reagents, and is applicable to scale-up syntheses as well as late-stage functionalization of drug molecules. The stereospecific coupling is also achieved from readily available optically enriched P(O)-H compounds.


Applications of blood-oxygen-level-dependent functional magnetic resonance imaging and diffusion tensor imaging in epilepsy.
The lifetime prevalence of epilepsy ranges from 2.7 to 12.4 per 1000 in Western countries. Around 30% of patients with epilepsy remain refractory to antiepileptic drugs and continue to have seizures. Noninvasive imaging techniques such as functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) have helped to better understand mechanisms of seizure generation and propagation, and to localize epileptic, eloquent, and cognitive networks. In this review, the clinical applications of fMRI and DTI are discussed, for mapping cognitive and epileptic networks and organization of white matter tracts in individuals with epilepsy.


The relationship between common mutations in CFTR, AR genes, Y chromosome microdeletions and karyotyping abnormalities with very severe oligozoospermia in Iranian men.
Male infertility due to very severe oligozoospermia has been associated with some genetic risk factors. To investigate the distribution of the mutations in the CFTR gene, the CAG-repeat expansion of the AR gene, also Y chromosome microdeletions and karyotyping abnormalities in very severe oligozoospermia patients. In the present case-control study, 200 patients and 200 fertile males were enrolled. All patients and control group were karyotyped. Microdeletions were evaluated using multiplex PCR. Five common CFTR mutations were genotyped using the ARMS-PCR technique. The CAG-repeat expansion in the AR gene was evaluated for each individual using sequencing. Overall 4% of cases shows a numerical and structural abnormality. 7.5% of patients had a deletion in one of the AZF regions on Yq, and 3.5% had a deletion in two regions. F508del was the most common (4.5%) CFTR gene mutation; G542X, and W1282X were detected with 1.5% and 1% respectively. One patient was found to have AZFa microdeletion and F508del in heterozygote form; one patient had AZFb microdeletion with F508del. F508del was seen as compound heterozygous with G542X in one patient and with W1282X in the other patient. The difference in the mean of the CAG-repeats in the AR gene in patients and control groups was statistically significant (P = 0.04). Our study shows the genetic mutations in men with severe oligozoospermia and given the possibility of transmission of these disorders to the next generation by fertilization, counseling and genetic testing are suggested for these couples before considering ICSI.


Detection and characterization of the novel HLA-DPA1*02:66:02N allele, with a premature stop codon in exon 2.
The failure to identify HLA null alleles in bone marrow transplantation could be life-threatening because this could result in an HLA mismatch with the ability to trigger the graft-vs-host disease (GVHD) and to reduce patient's survival. In this report we describe the identification and characterization of the novel HLA-DPA1*02:66:02N allele with a non-sense codon in exon 2. This new allele was discovered in two unrelated bone marrow donors during routine HLA-typing using next-generation sequencing (NGS). DPA1*02:66:02N is homologous to DPA1*02:01:01:03 with a single nucleotide difference in exon 2, codon 50, where the replacement of C located at genomic position 3825 by T, causes the formation of a premature stop codon (TGA), resulting in a null allele. This description illustrates the benefits of HLA typing by NGS since it permits to reduce ambiguities, identify new alleles, analyze multiple HLA loci and improve transplantation outcome.


Effects of implementing family-centered rounds (FCRs) in a neonatal intensive care unit (NICU).
(1) Evaluate impact of FCR on provider satisfaction and collaboration. (2) Evaluate impact of FCR on parent satisfaction with provider communication. Collaboration and Satisfaction about Care Decisions (CSACD) questionnaire was given to staff on 4 patients 2 days a week for 5 weeks prior to and 6 months after implementation of FCR. Parents received a Parents Stress Scale and Neonatal Instrument of Parent Satisfaction before discharge, prior to and 6 months after starting FCR. 278/288 (97%) staff surveys were completed, 142 pre and 136 post. On the CSACD survey NNPs and fellows showed increased (p < 0.05) collaboration and satisfaction post FCR. No group had decreased satisfaction. Twenty-eight of 45 (62%) parent surveys were completed, 12 pre and 16 post. Parents' satisfaction scores increased (p < 0.01) pre vs. post on survey items regarding communication, meeting with physicians, and obtaining information about their infants. FCR was associated with enhanced collaboration among team members for NNPs and fellows. Parents' satisfaction scores increased post FCR on survey items regarding communication. Since NNPs and fellows are the primary communicators with parents, the increased satisfaction may reflect improved communication due to FCR. This added opportunity for open dialogue may also contribute to the increased parent satisfaction.


Influence of plerixafor on the mobilization of CD34+ cell subpopulations and lymphocyte subtypes.
Peripheral blood stem cells mobilized with granulocyte-colony-stimulating factor (G-CSF) with or without chemotherapy are routinely used for autologous hematopoietic cell transplantation. Plerixafor, a chemokine-receptor inhibitor, increases the amount of circulating CD34+ cells and improves harvest results. However, limited information is available regarding the composition of apheresis products with respect to CD34+ and lymphocyte subtypes collected after various mobilization regimens. We used a recently established single-platform multicolor flow-cytometric analysis including CD45RA and CD133 to define CD34+ subpopulations and lymphocyte subsets in products obtained either after G-CSF with or without chemotherapy alone (G, n = 40) or with addition of plerixafor (GP, n = 40). Absolute numbers of white blood cells and lymphocyte subtypes were significantly higher after plerixafor, which was not observed for absolute CD34+ counts. However, distinct differences in terms of CD34+ subtypes were observed. The most primitive multipotent progenitors (CD45RA-CD133+CD34+CD38low ) predominated significantly after G (median, 49.2%; range, 15.2%-63%) compared to GP (median, 34.4%; range, 12%-62%; p < 0.001), whereas more differentiated subsets clearly prevailed after GP. In contrast to the findings of other authors, our study shows a clear shift toward more committed CD34+ subsets after plerixafor in poor mobilizers and elucidates the importance of informative surface markers like CD45RA and CD133 in addition to CD38 to discriminate earlier from more committed CD34+ cells. Further studies are needed to analyze whether these findings have an impact on clinical outcome.


Participation as an outcome measure in psychosocial oncology: content of cancer-specific health-related quality of life instruments.
To examine to what extent the concept and the domains of participation as defined in the International Classification of Functioning, Disability and Health (ICF) are represented in general cancer-specific health-related quality of life (HRQOL) instruments. Using the ICF linking rules, two coders independently extracted the meaningful concepts of ten instruments and linked these to ICF codes. The proportion of concepts that could be linked to ICF codes ranged from 68 to 95%. Although all instruments contained concepts linked to Participation (Chapters d7-d9 of the classification of 'Activities and Participation'), the instruments covered only a small part of all available ICF codes. The proportion of ICF codes in the instruments that were participation related ranged from 3 to 35%. 'Major life areas' (d8) was the most frequently used Participation Chapter, with d850 'remunerative employment' as the most used ICF code. The number of participation-related ICF codes covered in the instruments is limited. General cancer-specific HRQOL instruments only assess social life of cancer patients to a limited degree. This study's information on the content of these instruments may guide researchers in selecting the appropriate instrument for a specific research purpose.


The contribution of testing in the fight against COVID-19: evidence from Italy.
In response to the epidemic of coronavirus disease 2019 (COVID-19), a few countries have rolled out widespread testing of the population, while in other countries only people requiring hospital admission are being screened. After an extensive testing strategy during the initial few weeks in the early phase of the epidemic, the Italian Ministry of Health made its testing policy more stringent. In this study we assess the contribution of the testing policy containing the spread of the COVID-19 epidemic in Northern Italy. The analysis is focused on the evolution of the epidemic and related health intervention in four regions where ∼80% of the national death toll due to COVID-19 has occurred. The assumed under-estimation of asymptomatic cases has led us to make use of the number of deaths due to the epidemic to analyze the effectiveness of testing. The analysis is conducted through an autoregressive time-series approach where we use official data from the Ministry of Health. The results of the analysis confirm a negative relationship between the number of tests carried out and the progression of the epidemic. In particular, results reveal that the tests are particularly effective in breaking the chain of transmission when they are implemented at the early stages of the spread of the virus. A large-scale testing policy is recommended as a critical contribution to effectively contain the epidemic. In addition, it is highly recommended to set up all necessary measures to enable the quick scale-up of testing capacity whenever required.


Spatially localized motion aftereffect disappears faster from awareness when selectively attended to according to its direction.
In searching for the target-afterimage patch among spatially separate alternatives of color-afterimages the target fades from awareness before its competitors (Bachmann, T., & Murd, C. (2010). Covert spatial attention in search for the location of a color-afterimage patch speeds up its decay from awareness: Introducing a method useful for the study of neural correlates of visual awareness. Vision Research 50, 1048-1053). In an analogous study presented here we show that a similar effect is obtained when a target spatial location specified according to the direction of motion aftereffect within it is searched by covert top-down attention. The adverse effect of selective attention on the duration of awareness of sensory qualiae known earlier to be present for color and periodic spatial contrast is extended also to sensory channels carrying motion information.


Identification of Predictors of Non-alcoholic Steatohepatitis and Its Severity in Individuals Undergoing Bariatric Surgery.
As obesity reached epidemic proportions, non-alcoholic fatty liver disease (NAFLD) also had a worrisome parallel increase. The non-invasive differentiation of non-alcoholic steatohepatitis (NASH) from uncomplicated NAFLD remains an important challenge in current clinical practice. To identify predictors of the occurrence and severity of NAFLD and NASH. This is an analytical cross-sectional study which included individuals undergoing bariatric surgery. Participants were histologically classified according to the presence NASH and severity of NAFLD. Demographic, clinical, anthropometric, and biochemical aspects were analyzed and compared. Out of 171 individuals, 87.7% were female and the mean age was 38.4±9.3 years. The average BMI was 38±3.0 kg/m2. NAFLD was histologically confirmed in 74.9%; the commonest histopathological abnormalities were macrovesicular steatosis (74.9%) and ballooning (40.4%). Simple steatosis occurred in 30.4%, 44.4% presented with NASH, and 31% had severe NAFLD. NASH associated with higher levels of ALT (0.03), ALP (0.02), and glucose (0.02). Cutoff values were, respectively, 23 U/L, 67 U/L, and 81 mg/dL. Their concomitant use provided an 83.1% specificity for NASH. Severe NAFLD associated with diabetes (p=0.02), higher BMI (p=0.01), AST (p=0.04), ALT (p<0.01), ALP (p=0.01), glucose (p=0.02), and ferritin (p<0.01). BMI over 39.3 kg/m2 and ferritin over 178 ng/mL concomitantly provided a 70.5% accuracy for severe NAFLD. NASH and severe NAFLD associated with higher levels of ALT, ALP, and glucose. Severe NAFLD associated with higher BMI and higher ferritin levels in this group. The concomitant evaluation of these laboratory tests could help ruling out NASH and safely screening severe NAFLD.


Experience of middle management nurses during the COVID-19 pandemic in Switzerland: A qualitative study.
To explore the experiences of middle management nurses during the COVID-19 pandemic in Switzerland. The outbreak of COVID-19 has placed extraordinary demands on health care systems worldwide, which were found mostly unprepared. In this situation, middle management nurses played a strategic role because they acted as a link between organizational directives and the clinical practice. This is a qualitative study that used a face-to-face interview with semi-structured questions to learn about the experiences of middle management nurses during the COVID-19 pandemic. After recruiting participants through purposeful sampling, data were analysed by means of thematic analysis using Nvivo 12. In total, 12 middle managers were interviewed. Data analysis identified four macro-themes-Changes; Conflicting emotions; Relation; Role-and 20 sub-themes. The sudden challenges posed by the pandemic required middle managers to shift their focus from advanced planning to negotiation for meeting the rapidly evolving needs of nursing staff and top management, in order to guarantee the nursing team's well-being and organizational efficiency. Lessons learned from the pandemic suggest the need for fine-tuning organizational models and the importance that nurse middle managers affirm and uphold the core values for nursing and engage patient and staff advocacy.


Communication between gastrointestinal bacteria and the nervous system.
In the past few years, intestinal microbiota has emerged as a novel target for the treatment of gut-brain axis alterations. These include functional gastrointestinal disorders, such as irritable bowel syndrome (IBS), which can be comorbid with stress-related psychiatric conditions. Thus, modulation of the microbiota (e.g. with the use of probiotics) could be proposed as a novel strategy not only for the treatment of IBS but also as an adjuvant for psychiatric treatment of anxiety and depression.


Antioxidants and proinflamatory cytokines in the sera of patients with cutaneous leishmaniasis.
Leishmania is a significant health problem in many parts of the world. Tumor necrosis factor (TNF) plays an essential role in Leishmania major infections. To study the pro-inflammatory cytokines and antioxidants in four groups of cutaneous leishmaniasis patients. 39 patients were divided into four groups of: 1) active (acute phase of treatment); 2) non-healing (received treatment for almost two years without recovery); 3) healing (recovered upon treatment); and 4) healed (previously received treatment and achieved complete remission) patients. Serum levels of pro-inflammatory cytokines (IL-1B, TNF-α, IL-6) and serum antioxidant levels were measured by ELISA and FRAP assays, respectively. While serum antioxidant levels were elevated in the non-healing group, there was no difference among other groups of patients and healthy controls in this regard. Interleukin-1β showed the highest level in the non-healing group followed by the other groups of patients. The mean serum IL-6 level was highest in the non-healing group, but showed no significant change in the other groups. TNF-α and IL-1β levels were non-significantly elevated in the sera of active and non-healing patients. Pro-inflammatory cytokines IL-1β, TNF-α, IL-6 maybe related to the progression of leishmaniasis. Serum antioxidant levels maybe correlated with patient response to drug treatment.