Non-erosive and erosive gastroesophageal reflux diseases: No difference with regard to reflux pattern and motility abnormalities.
To investigate whether gastroesophageal reflux disease (GERD) with mild to moderate erosive esophagitis (ERD) is a more severe disease regarding the amount of acid reflux, motor abnormalities, and the presence/absence of hiatus hernia than non-erosive reflux disease (NERD). The study comprised a retrospective analysis of prospectively collected data on 313 consecutive subjects referred for endoscopy, pH-metry, and esophageal manometry. The patients were divided into four groups: Group I (n=92), subjects without GERD with normal pH-metry, without esophagitis and without reflux symptoms; Group II (n=111), patients with NERD (no esophagitis, abnormal pH-metry); Group III (n=77), patients with mild to moderate ERD (LA A, B; abnormal pH-metry); Group IV (n=33), patients with severe or complicated esophagitis (LA C, D; Barrett's esophagus). All data are expressed as medians with 5th-95th percentiles. No difference was found in the amount of acid reflux between patients with mild to moderate ERD and those with NERD. The DeMeester score was 34.5 (17-105) in NERD patients and 31.6 (15-102) in ERD patients. No significant differences were found between NERD and ERD patients regarding lower esophageal sphincter (LES) basal pressure (11.6 mmHg; 3-25 in NERD versus 10.7 mmHg; 3-22 in ERD). Similar proportions of patients with NERD and ERD had low LES basal pressure (20.7% in NERD versus 24.7% in ERD; NS) and hiatus hernia (44% and 56%; NS). A relatively high proportion of patients without GERD (Group I) had ineffective esophageal motility (39%) and hiatus hernia (30%). No difference was found between NERD and mild to moderate ERD in terms of acid exposure time and esophageal motor abnormalities. To a certain extent, ERD is a "more complicated" form of the disease. Host factors related to a particular patient (e.g. mucosal defense, genetics, acid clearance) might be responsible for the development of esophagitis.


Exposure of basement rock on the continental slope of the bering sea.
Profiles of repetitive seismnic reflections reveal that the Bering con tinental slope, outer shelf, and rise overlay an acoustically reflective "basement" which extends at least 750 kilometers parallel to the trend of the slope. This acoustic basement is usually covered by several hundred meters of stratified sediments at the top and bottom of the slope; however, it is exposed in sub marine canyons and flanking spurs along the main part of the slope for a distance of at least 550 kilometers northwest of the Pribilof Islands. The lithologic composition and the age of the rocks of the acoustic basement are not known. However, its probable seismic velocity of 3.1 to 3.7 kilometers per second suggests that it is composed of volcanic rocks or lithified sedimentary rocks or both. The regional geology suggests that the acoustic basement is the upper surface of folded late Mesozoic rocks which were locally intruded by granite and serpentine. The structure of the Bering slope, as deduced from the acoustic profiles, suggests that the surface of the basement has been monoclinically flexed and faulted between the shelf edge and the deep Aleutian Basin.


Coincidence of conchachoanal polyp and complete mulberry hypertrophy of inferior concha.
We report two unique cases of 50- and 28-year-old Turkish men with coincidence of conchachoanal polyp and mulberry hypertrophy of the inferior concha. We operated on both cases with endoscopic stripping of the polypoid tissue while preserving the periosteum and healthy mucosa of the inferior nasal concha. The polypoid tile of the left inferior nasal concha was resected in the case with mulberry hypertrophy at only the tail of the concha. Both cases reported significant relief of symptoms after the operations.


[Analysis of illness pathology causes of digestive organs in the Chuvash Republic and prospects of its reduction].
The main principles of organization of gastroenterological service of the Chuvash Republic are presented. The main significant causes of incidence rate of digestive apparatus pathology and the ways of their elimination are discussed. The peculiarities of population dietary habits are analyzed. The complex of measures carried out in Chuvashia for improving the quality of production and processing of alimentary products taking into account the peculiarities of every biogeochemical subregion and requirements of various population groups is presented. The forms and methods of healthy life-style formation, training of people responsible attitude to their health are described. Priority guidelines of gastroenterological assistance to the population of the Chuvash Republic are enumerated.


Mapping communities as complex adaptive systems: A study of the response to violence against women by communities in Samoa.
This paper explores the concept of communities as complex adaptive systems in the context of violence against women (VAW) prevention. Using thematic network analysis on data from 80 semi-structured interviews with community members in Samoa, we found that communities exhibit many properties of complex adaptive systems. Within nested systems, diverse and dynamic agents interact based on their knowledge and attitudes, which changes over time, leading to emergent and unpredictable outcomes. The functioning of communities and their response to VAW is a product of non-linear and emerging relationships and interactions between systems components at the community level. The approach we propose for conceptualising communities as complex adaptive systems provides a structured method for designing and evaluating community-based interventions that are grounded in the local context and existing resources. With in-depth knowledge of how a community works, interventions can be better equipped to address wicked problems such as VAW.


[Concept of labile protein and the adaptation of nitrogen metabolism in protein deficiency in man].
Investigations involving 30 healthy males, who for 45 days consumed standard semisynthetic diets differing in the caseine content (from 0 to 15.1 g of nitrogen per day) and serving as a sole source of protein, furnished data on the nitrogen excretion kinetics and nitrogen balance. Mathematical analysis of these data allowed it to find the existence of general regularity in the nitrogen excretion and to deduce an integral equation of its losses at different levels of nitrogen consumption. Pertinent calculations have ascertained that by the labile protein one should understand not the specific proportion of the total protein in the organism, but the actual rate of its metabolism, manifesting itself in the routine lag-phase during adaptation of the nitrogen metabolism to a new level of the protein allowances in the organism. The data thus made available permitted it, at the same time, to propose a criterion for estimating the optimal requirements of man in proteins.


Detection of Apolipoprotein E Gene Polymorphism and Blood Lipid Level in Hemodialysis Patients.
The aim was to investigate the clinical characteristics of lipid metabolism and the effect of apolipoprotein E (ApoE) gene polymorphism on lipid metabolism in hemodialysis patients. The serum levels of total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDLC), low-density lipoprotein cholesterol (LDLC), ApoA1, ApoB, ApoE and lipoprotein Lp(a) were detected by polymerase chain reaction-restriction fragment length (PCR-RFLP). The level of serum TG was significantly increased and the level of HDLC was significantly decreased in hemodialysis patients. Serum TG level was 33% higher than normal, and HDLC was 10.4% less than normal. The correlation analysis showed that TG level was significantly correlated with serum albumin level and extracorporeal circulation blood flow during dialysis. HDLC was significantly correlated with KT/V. The incidence of hypertension in hemodialysis patients was 73.6% and cardiovascular disease was 25%. The level of TG in the cardiovascular disease group was significantly higher than that in the non-cardiovascular disease group, and there was no significant difference between the hypertensive group and the non-hypertensive group. ApoE gene polymorphism test showed that the frequency of ApoE genotype ε3/3 and allele ε3 was the highest in hemodialysis patients, and the levels of TC, TG and LDLC were higher in ApoE genotype ε3/4 + ε4/4. The levels of serum TG and ApoB were significantly increased in patients with hemodialysis, and HDLC and other indexes were significantly decreased. The level of TG in patients with cardiovascular complications was significantly higher than in patients without complications. TG level was significantly correlated with serum albumin level and extracorporeal circulation blood flow during dialysis. HDLC was significantly correlated with KT/V. Hemodialysis patients who had ApoE allele ε4 are prone to lipid metabolism disorders.


The investigation of the educational needs on the job competence for physical therapist assistant in the students of Quang Tri medical college in Vietnam.
[Purpose] The purpose of this study was to investigate the educational needs on the job competence for physical therapist assistant in the students of Quang Tri medical college in Vietnam. [Participants and Methods] Participants consisted of 17 individuals in the educational program for physical therapist assistant in Quang Tri medical college. The importance recognition ranking and current levels were measured by self-assessment for job competence of physical therapist assistant using a questionnaire. The educational needs were calculated by importance recognition ranking and current level by a self-assessment of job competence. [Results] The importance recognition ranking of job competence appeared to show a 'system checkup' as the top ranked category. The rank of current levels of competencies was determined by self-assessment of job competence and results showed that 'cooperation, communication, and documentation' was the highest category of the current levels. The highest rank of the educational needs was 'counseling and education'. [Conclusion] The educational needs rank of job competence appeared to be 'counseling and education' foremost. Counseling and education with the patient is a fundamental component of effective healthcare. Therefore, it should be considered a priority for the educational curriculum of physical therapist assistant.


Magnetic resonance detection: spectroscopy and imaging of lab-on-a-chip.
This mini-review is focused on the use of nuclear magnetic resonance (NMR) spectroscopy and imaging to study processes on lab-on-a-chip devices. NMR as an analytical tool is unmatched in its impact across nearly every area of science, from biochemistry and medicine to fundamental chemistry and physics. The controls available to the NMR spectroscopist or imager are vast, allowing for everything from high level structural determination of proteins in solution to detailed contrast imaging of organs in-vivo. Unfortunately, the weak nuclear magnetic moment of the nucleus requires that a very large number of spins be present for an inductively detectable signal, making the use of magnetic resonance as a detection modality for microfluidic devices especially challenging. Here we present recent efforts to combat the inherent sensitivity limitation of magnetic resonance for lab-on-a-chip applications. Principles and examples of different approaches are presented that highlight the flexibility and advantages of this type of detection modality.


Growth characteristics and ultrastructure of human retinal pigment epithelium in vitro.
The in vitro growth characteristics and morphology of human retinal pigment epithelium (RPE) cells from adult donor eyes (15 to 100 years of age) have been studied. Although RPE cells are viable in culture for several months, only a fraction of the cells actually divide. Rapid cell proliferation and confluency of a culture occur from 10 to 30 days after seeding. The time for confluency is both age- and media-dependent; the number of cells that are potential dividers and contribute to confluency decreases with increasing donor age. Since melanolipofuscin granules do not form in vitro and are diluted by cell division, stationary (nondividing) cells can be distinguished from the dividing cells by the presence of dense clusters of melanolipofuscin granules in the stationary cells. Confluent cultures contain a monolayer of relatively clear polygonal cells with densely pigmented stationary cells scattered throughout. Stationary cells can often represent as much as 95% of the original RPE cell population. Ultrastructurally all cells appear epithelioid, with apical-basal polarity, junctional complexes, and cytoplasmic organization characteristic of RPE cells in vivo. Stationary cells are extremely large, with melanolipofuscin granules clustered around the nucleus. Melanolipofuscin is a unique marker for nondividing cells and may facilitate studies of the age-dependent loss of replicability of human RPE.


[Immunochemical study of modified forms of L-asparaginase].
Certain catalytic and immunological properties of L-asparaginase modified by polyglucin were studied. It was shown that the modified forms of L-asparaginase maintained high catalytic activity (Km 0.80.10(-5)-1.89.10(-5) M) and at the same time appeared to be more resistant to inactivation under the effect of antibodies.


Cost-Effectiveness Analysis of Deep Brain Stimulation for Parkinson Disease in Taiwan.
Deep brain stimulation of the subthalamic nucleus (STN-DBS) is an effective therapy for Parkinson disease (PD). However, cost-effectiveness analysis is required because most patients are older adults and decision makers must therefore consider whether the long-term effectiveness outweighs the initial cost. A Markov decision model was constructed on the basis of a societal perspective. The Hoehn and Yahr scale and Unified PD Rating Scale motor score were used in the polytomous logistic regression model. Markov Chain Monte Carlo simulation was used to initiate the probabilistic cost-effectiveness analysis. The life-year gained (LYG) in the STN-DBS group and medication group was, respectively, 2.937 and 2.632 years at the 3-year follow-up and 7.417 and 5.971 years at the 10-year follow-up. The quality-adjusted life-year (QALY) gained in the STN-DBS and medication groups was, respectively, 1.739 and 1.220 at the 3-year follow-up and 4.189 and 2.88 at the 10-year follow-up. The incremental cost-effectiveness ratio of STN-DBS compared with medication was $147,065 per LYG and $123,436 per QALY gained at the 3-year follow-up and $36,833 and $69,033 at the 10-year follow-up, respectively. STN-DBS is an optimal strategy when the willingness to pay is $150,000 per LYG and over $90,000 per QALY gained in 3 years and when the willingness to pay is over $38,000 per LYG and over $41,000 per QALY gained in 10 years. This study provided data comparing STN-DBS and medical treatment for PD with respect to LYG and QALY gained. STN-DBS was more cost-effective in terms of LYG and QALY gained according to the current gross domestic product of Taiwan.


A near-infrared phosphorescent iridium(iii) complex for fast and time-resolved detection of cysteine and homocysteine.
Thiol-containing amino acids, cysteine (Cys) and homocysteine (Hcy), play crucial roles in the biosystem; their abnormal contents in the cells are linked to many diseases. Herein, we designed and synthesized a novel near-infrared (NIR) phosphorescent iridium(iii) complex-based probe (FNO1) that can detect Cys and Hcy in real-time in the biosystem. Due to the advantages of the iridium complex, the FNO1 probe had excellent chemical stability and photostability, high luminescence efficiency, and long luminescence lifetime. In addition, the probe showed a fast response, high sensitivity, and low cytotoxicity. As verified by high resolution mass spectra (HR-MS) and density functional theory (DFT) calculations, the detection was achieved through the addition of the α,β-unsaturated ketone group in FNO1 by the nucleophilic thiol group in Cys and Hcy. Through time-resolved emission spectroscopy (TRES) and in the presence of a strongly fluorescent dye rhodamine B, the FNO1 probe could detect Cys and Hcy due to its long luminescence lifetime (260/197 ns). Finally, owing to its NIR-emitting properties, the FNO1 probe was successfully applied in the imaging of Cys and Hcy in living cells, zebrafish, and mice.


Hairy cell leukemia and COVID-19 adaptation of treatment guidelines.
Standard treatment options in classic HCL (cHCL) result in high response rates and near normal life expectancy. However, the disease itself and the recommended standard treatment are associated with profound and prolonged immunosuppression, increasing susceptibility to infections and the risk for a severe course of COVID-19. The Hairy Cell Leukemia Foundation (HCLF) has recently convened experts and discussed different clinical strategies for the management of these patients. The new recommendations adapt the 2017 consensus for the diagnosis and management with cHCL to the current COVID-19 pandemic. They underline the option of active surveillance in patients with low but stable blood counts, consider the use of targeted and non-immunosuppressive agents as first-line treatment for cHCL, and give recommendations on preventive measures against COVID-19.


Characterization of the cell death induced by cadmium in HaCaT and C6 cell lines.
Cell death resulting from cadmium (Cd) intoxication has been confirmed to induce both necrosis and apoptosis. The ratio between both types of cell death is dose- and cell-type-dependent. This study used the human keratinocytes HaCaT expressing a mutated p53 and the rat glial cells C6 expressing a wild p53 as models to characterize Cd-induced apoptosis, using sub-lethal and lethal doses. At these concentrations, features of apoptosis were observed 24 h after C6 cell treatment: apoptotic DNA fragmentation and caspase-9 activation, whereas Cd did not induce caspase-3. In HaCaT, Cd did not induce apoptotic DNA fragmentation or caspase-9 and -3 activation. The results also showed that the inhibition of p53 led to a resistance of the C6 cells to 20 microm Cd, decreased the apoptosis and increased the metallothioneins in these cells. p53 restoration increased the sensitivity of HaCaT cells to Cd but did not affect the MT expression. The results suggest that Cd induced apoptosis in C6 cells but a non-apoptotic cellular death in HaCaT cells.


Does completion thyroidectomy improve the outcome of patients with minimally invasive follicular carcinoma of the thyroid?
The diagnosis of minimally invasive follicular thyroid carcinoma (MIFTC) is often made histologically after thyroid lobectomy. We attempted to determine whether completion thyroidectomy should be considered necessary for all patients diagnosed with MIFTC after thyroid lobectomy. The subjects of this study were a total of 324 patients who underwent thyroid lobectomy as initial surgery at our institution between 1989 and 2010 and diagnosed histologically as MIFTC. Completion thyroidectomy was performed on 101 patients, and the other 223 patients were followed up without further treatments. Cumulative cause-specific survival (CSS) rates and distant-metastasis-free survival (DMFS) rates were calculated by the Kaplan-Meier method. Differences between groups were analyzed for statistical significance by the log-rank test. Multivariate analysis was performed by using the Cox proportional hazards model. During the follow-up period, 39 patients were diagnosed with distant metastasis, and 7 patients died of their disease. Age at the initial surgery was found to be a significant factor related to DMFS in both the univariate and multivariate analysis and to also be related to CSS in the univariate analysis. Completion thyroidectomy did not have a significant effect on DMFS or CSS according to the results of the univariate analysis, but it had significant effect on DMFS according to the results of the multivariate analysis. Although we were unable to demonstrate sufficient statistical evidence that completion thyroidectomy improved the outcome of MIFTC patients, it is noteworthy none of the patient who underwent completion thyroidectomy died of the disease.


Emotional regulation strategies (ER) used by trainees to overcome negative emotions.
To identify the use of different emotion regulation strategies by medical trainees, and to determine the frequency and the predominant pattern of emotional response in emotion-triggering situations. The descriptive cross-sectional study was conducted at 2 public and 1 private medical college in Lahore, Pakistan, from March to September 2019, and comprised postgraduate medical trainees of either gender from all clinical disciplines from years 1-4. Data was collected using a questionnaire based on the Gross theory of emotional regulation and the Situational model of emotion. Emotion regulation strategies included situation selection, situation modification, cognitive change, attention deployment, and response modulation. Data was analysed using SPSS 25.. Of the 377 trainees approached, 308(81.69%) participated; 206(67%) females and 102(33%) males. The overall mean age was 27.8 ± 2.91 years. The majority of the trainees were from the Obstetrics and Gynaecology department 133(43.2%) and were in the first year of their training 116(37.7%). The most frequent emotiontriggering situation identified was prolonged working hours 292(95%), and the major emotional response was quietness in 5 out of ten situations (50%). The trainees used greater emotion regulation strategies in sad situations 3.49±1.79 (p<0.01). Trainees managed sad emotions by keeping themselves involved in other activities 152 (49%); in anger, they blamed others 124(40.3%); in fear, they opted for suppression of emotions 71(22.7%); in disgust, they preferred avoidance 90(29.2%); and in shock, acceptance was a common strategy 21(12.7%). Postgraduate medical trainees struggled to manage emotions and used maladaptive strategies.


Prodromes of depression and anxiety. The Stirling County study.
A longitudinal investigation of psychiatric epidemiology in a general population (the Stirling County study) has indicated that the incidence of depression and anxiety disorders is low relative to prevalence, because these disorders have long durations. In an average year approximately nine adults among 1,000 experience a first-ever episode of one of these disorders. Incident cases over the course of a 16-year follow-up were more likely to have had premonitory symptoms than to have been asymptomatic at the beginning of the study. Among the relatively small number of people who exhibited the clearest prodromal manifestations, incidence was 20 per 1,000 annually. It might be possible to intervene before such disorders become fully formed and persistent if the precursors are given attention.


A prospective evaluation of a clinical algorithm for the diagnosis of malaria in Gambian children.
Diagnosis of clinical malaria remains difficult, especially in areas where a high proportion of the asymptomatic population have parasitaemia, for the symptoms and signs of malaria overlap with those of other common childhood diseases, such as acute lower respiratory tract infections. However, a study of symptoms and signs in a group of children who presented to Farafenni Health Centre, The Gambia with a history of recent fever identified a group of signs and symptoms which were strong predictors of malaria as opposed to other febrile illnesses. Using these predictors, an algorithm was developed which could be used by fieldworkers and which had a similar sensitivity and specificity for the diagnosis of malaria as that of an experienced paediatrician working without laboratory support. This algorithm has been validated prospectively on 518 children who presented to the Medical Research Council clinic at Basse, The Gambia with fever or a history of recent fever during a 10-month period. A fieldworker obtained a detailed history from the parent or guardian of each child and performed a clinical examination which included measurement of axillary temperature and respiratory rate. Packed cell volume was measured and a thick smear was examined for malaria parasites. A malaria score, based on the presence or absence of malaria-related signs and symptoms, was determined for 382 children who were seen at the clinic during the high transmission season. Using the cut-off score which was optimal during the previous retrospective study, a sensitivity of 70% and a specificity of 77% for a diagnosis of malaria was obtained. The optimal cut-off score for the Basse population was a score of 7; this gave a sensitivity of 88% and a specificity of 62%, figures comparable to those obtained by an experienced paediatrician without laboratory support.


Sodium and lithium movements and axonal function in cockroach nerve cords.
Exposure to sodium-deficient (tris) saline caused an appreciable decline in the sodium content of intact connectives in the absence of equivalent reduction in the amplitude of the recorded action potentials. Return of sodium-depleted connectives to normal saline resulted in a rapid recovery of axonal function despite only a partial (less than 70%) recovery in sodium content. Replacement of sodium ions by those of lithium in the bathing medium resulted in a substantial accumulation of this cation. Lithium movements exhibited a marked asymetry, no significant decline in concentration being observed upon return to normal saline. These results are tentatively interpreted in terms of an exchangeable glial sodium fraction and are discussed in relation to extra-axonal sodium regulation.


Carotid thin fluttering bands: A new element of arterial wall remodelling? An ultrasound study.
Carotid artery ultrasound is a non-invasive and reproducible technique used for early atherosclerotic assessment. Intimal flap has been described in the presence of dissection or mobile plaque rupture, however presence of carotid thin fluttering bands (TFBs) have not been described yet. To investigate frequency, characteristics and impact of TFBs in carotid lumen of patients who underwent carotid ultrasound scan (CUS). 3341 patients were admitted from January 2009 to January 2014. Patients with history of cerebral ischemia (CI) were excluded. In the cases in which TFBs were observed, a 3-months clinical and CUS follow-up (FU) was performed. TFBs were found in 71 patients (2.1%). The mean age was 63.41 ± 11.20 years (range 42-89). All patients showed a mean increase in intima-media thickness. We identified two subgroups: in 22 patients the TFB was related to a carotid plaque while in 49 no carotid plaque was found. TFB mostly originated in the carotid bulb (88.7%) and was similarly located in carotid arteries (49.3% left-side and 50.7% right-side). CUS and clinical FU were available for all patients (mean duration 25.34 months, median 19). CI occurred in none of the patients. TFB disappeared in 13 patients (18.3%) with no sign or symptoms of CI. In 3 of 49 patients without carotid plaque (6.1%), progressive thickening beneath TFB was observed. TFB is a rare finding. Longer FU is needed to evaluate its prognosis. To date, the pathophysiology is unknown, however it could be related to vascular remodeling.


Comparison of SA nodal and subsidiary atrial pacemaker function and location in the dog.
A 3-4 cm length of sulcus terminalis tissue including the sinoatrial node (SAN) was excised from 14 dogs. After an initial junctional rhythm with SAN excision a P wave emerged within days to weeks in 12 animals. Maximum heart rates of the SAN (preoperative) in response to exercise (276 +/- 15 beats/min), isoproterenol infusion in conscious animals (272 +/- 11 beats/min), and stellate stimulation during anesthesia (273 +/- 9 beats/min) were significantly greater than subsidiary pacemakers (postoperatively) for exercise (219 +/- 9 beats/min), isoproterenol (226 +/- 8 beats/min), and stellate stimulation (197 +/- 9 beats/min). During a final experiment, electrophysiological mapping of the area of earliest epicardial activation (pacemaker location) was carried out. By use of a suction electrode in reference to plunge electrodes located in the anterior interatrial band (AIB), eustachian ridge of the coronary sinus, and limbus of the fossa ovalis, the pacemaker was located at the inferior vena cava-inferior right atrial junction in 80% of the animals mapped. During isoproterenol infusion the foci shifted to regions of the AIB in 70% of the animals mapped. The concept of pacemaker hierarchy is discussed.


The ability of pretransplant test-dose pharmacokinetic profiles to reduce early adverse events after renal transplantation.
Pretransplant test-dose pharmacokinetic profiles were used to determine individual cyclosporine drug bioavailability and clearance rates in renal transplant patients. Assuming a linear relation between dose and area under the concentration curve (AUC), starting i.v. and p.o. CsA doses were computed from the test-dose results. Target values were 400 ng/ml steady-state concentration (Css) during continuous intravenous infusion, and 500 ng/ml average drug concentration (Cavss = AUC/dosing interval) after oral administration, based upon measurements with the specific monoclonal antibody 3H-tracer radioimmunoassay. The outcomes after dose individualization with a 1-(n = 32), 2-(n = 38), or 3-(n = 41) hr i.v. infusion test dose and a p.o. test dose (n = 111) were compared with 228 historical control patients who received a uniform protocol of CsA i.v. at 2.5 mg/kg/day and p.o. at 14 mg/kg/day. The observed Css after i.v. CsA was within 10% of the target concentration in 73% of recipients tested with the 3-hr protocol, a significantly greater fraction than achieved with either the uniform dose (14%), or the 1-(34%) and 2-(25%) hr protocols. Patients in the 3-hr protocol group showed reduced incidences of delayed graft function, early graft loss, and rejection episodes, and a lower mean serum creatinine value, particularly at 7 but also at 30 days posttransplantation. Administration of the predicted oral dose produced a peak concentration of greater than or equal to 700 ng/ml drug absorption in 60% of recipients at 3 days, 90% at 5 days, and 98% at 7 days. The test-dose method less effectively predicted the appropriate oral CsA dose to produce target Cssav and failed to reduce the 90-day rejection incidence. Despite its limitations with the more-complicated p.o. route, the test-dose method successfully predicts i.v. CsA doses, thereby reducing the incidence of early adverse events.


A quantitative review of the use of FDG-PET in the axillary staging of breast cancer.
Breast cancer is the most frequent type of cancer in women and is the second leading cause of cancer death in Canadian women. It is an important source of morbidity and mortality in today's society and confers risk to the patient both in terms of the disease itself and the treatment of the disease. Axillary lymph node status is the most important prognostic factor for determining breast cancer survival and it guides the treatment of the disease based on the disease stage. The aim of this study is to assess the diagnostic value of positron emission tomography (PET) utilizing [18F]2-fluoro-2-deoxy-D-glucose (FDG) in the axillary staging of breast cancer. A systematic literature search was carried out in the Medline, Embase and Cochrane databases. Seventy one original studies were identified, 20 of which evaluated the axillary status of women. The studies were graded based on recommended procedures from similar studies. Aggregate sensitivities and specificities were calculated for various levels of quality for all included studies. Recommendations for future studies were made based on patient positioning, acquisition time, attenuation correction, fasting state, and image interpretation. A large variation in the sensitivity and specificity of large diagnostic trials of similar quality was noted. We concluded that PET has promise for the axillary staging of breast cancer once the variability of sensitivity and specificity in these large trials is addressed.


Epidemiology of community-acquired pneumonia in adults: a population-based study.
In this prospective study, the authors assessed the incidence, aetiology, and outcome of patients with community-acquired pneumonia in the general population. From December 1993 to November 1995, a study was performed in a mixed residential-industrial urban population of the "Maresme" region in Barcelona, Spain. All subjects > or =14 yrs of age (annual average population size 74,368 inhabitants) with clinically suspected community-acquired pneumonia were registered. All cases were re-evaluated by chest radiographs on the 5th day of illness and at monthly intervals until complete recovery. Urine and blood samples were obtained for culture and antigen detection. When lower respiratory tract secretions were obtained, these were also cultured. There were 241 patients with community-acquired pneumonia, with an annual incidence rate of 1.62 cases (95% confidence interval, 1.42-1.82) per 1,000 inhabitants. Incidence rates increased by age groups and were higher in males than in females. Of 232 patients with aetiological data, 104 had an identifiable aetiology. A total of 114 pathogens were found (single pathogen 94, two pathogens 10). There were 81 episodes of bacterial infection and 33 of viral infection. The most common pathogens were Streptococcus pneumoniae, Chlamydia pneumoniae, and influenza A and B viruses. No case of Hantavirus infection was found. The rate of hospital admission was 61.4% with a mean+/-SD length of 11.7+/-10.1 days, a mean period of 23.0+/-14.3 days inactivity, and an overall mortality rate of 5%. The high rate of hospital admission, prolonged stay in hospital, and long period of inactivity all continue to constitute a social and health care burden of community-acquired pneumonia.


Use of chronological and adjusted ages to compare motor development of healthy preterm and fullterm infants.
To investigate the influence of gestational age at birth on motor development in infancy and the practice of basing motor assessments of preterm infants on an adjusted age, 21 healthy preterm and 23 fullterm infants were administered the Peabody Developmental Motor Scales at 12, 15 and 18 months of age. When quotients were based on chronological age, both the mean gross-motor and fine-motor developmental quotients of the fullterm group were significantly higher than those of the preterm group, indicating that the fullterm group had higher levels of motor development. However, when the quotients of the preterm group were based on adjusted age, which accounted for gestational age at birth, the motor quotients of the two groups did not differ significantly. It seems that motor development of healthy preterm and fullterm infants differs primarily as a function of gestational age at birth, which supports maturational theory and the practice of making age adjustments when evaluating motor development of preterm infants.


Double-labeling of experimental acute myocardial infarcts with 113mIn- and 99mTc-EDTMP.
The feasibility of double-labeling of acute myocardial infarcts with 113mIn-EDTMP [ethylenediaminetetra(methylene phosphonic acid)] and 99mTc-EDTMP was evaluated. The in vitro distributions of these tracers in acute myocardial infarcts in dogs and their selectivities for infarcted versus noninfarcted myocardium were compared. Both tracers concentrated in acutely infarcted myocardium, and there was excellent correlation between their uptakes (r = 0.88). They also provided complete separation between infarcted and uninfarcted tissue, as checked by histology. Accordingly, these agents show promise for the multiple-labeling of acute myocardial infarcts in experiments to determine the natural course of myocardial infarction and the efficacy of therapy aimed at limiting infarct size. In addition, 113mIn-EDTMP may be useful for serial scintigraphy during the early phase of acute myocardial infarction when the damage may be, at least to some extent, reversible.


Antecedents of cerebral palsy in a multicenter trial of indomethacin for intraventricular hemorrhage.
To determine if cerebral palsy (CP) rates were lower in the active treatment group compared with the control group, as improved survival rates of very low-birth-weight infants are postulated to be the cause of the increased incidence of CP in preterm infants, to evaluate relationships between multiple prenatal, perinatal, and postnatal variables and CP to understand better its antecedents in very low-birth-weight infants in the era of surfactant replacement therapy, and to determine the usefulness of a cranial ultrasonographic (US) scan in predicting CP. Inception cohort follow-up study as part of a randomized controlled trial of low-dose indomethacin sodium for the prevention of intraventricular hemorrhage. Neonatal intensive care units at 3 medical centers. Infants with birth weights between 600 and 1250 g were eligible, and 505 infants were enrolled in the original study. Of these infants, 440 (87%) survived; neurologic examinations were completed on 381 infants (86%) at 36 months corrected age. Statistical analyses were performed to identify the antecedents of CP, including the results of frequent cranial US scans obtained throughout the newborn period. Cerebral palsy was found in 36 (9.5%) of 381 infants at 36 months corrected age (range, 33-39 months corrected age). Univariate analysis identified chorioamnionitis, treatment with surfactant, bronchopulmonary dysplasia, and abnormal cranial US findings as antecedents of CP. Periventricular leukomalacia and ventriculomegaly were associated with the highest detection rates for CP (37% and 30%, respectively) with acceptable false-positive rates. Multivariate analysis identified bronchopulmonary dysplasia and an abnormal cranial US scan showing grade 3 to 4 intraventricular hemorrhage, periventricular leukomalacia, or ventriculomegaly as independent predictors of CP. Odds ratios for the detection of CP using cranial US findings tabulated by hospital day were in the range of 7 to 26 beginning on day 2. The results suggest that cranial US findings are useful predictors of CP during a patient's stay in the hospital.


Visualization of conventional outflow tissue responses to netarsudil in living mouse eyes.
Visual impairment due to glaucoma currently impacts 70 million people worldwide. While disease progression can be slowed or stopped with effective lowering of intraocular pressure, current medical treatments are often inadequate. Fortunately, three new classes of therapeutics that target the diseased conventional outflow tissue responsible for ocular hypertension are in the final stages of human testing. The rho kinase inhibitors have proven particularly efficacious and additive to current therapies. Unfortunately, non-contact technology that monitors the health of outflow tissue and its response to conventional outflow therapy is not available clinically. Using optical coherence tomographic (OCT) imaging and novel segmentation software, we present the first demonstration of drug effects on conventional outflow tissues in living eyes. Topical netarsudil (formerly AR-13324), a rho kinase/ norepinephrine transporter inhibitor, affected both proximal (trabecular meshwork and Schlemm's Canal) and distal portions (intrascleral vessels) of the mouse conventional outflow tract. Hence, increased perfusion of outflow tissues was reliably resolved by OCT as widening of the trabecular meshwork and significant increases in cross-sectional area of Schlemm's canal following netarsudil treatment. These changes occurred in conjunction with increased outflow facility, increased speckle variance intensity of outflow vessels, increased tracer deposition in conventional outflow tissues and decreased intraocular pressure. This is the first report using live imaging to show real-time drug effects on conventional outflow tissues and specifically the mechanism of action of netarsudil in mouse eyes. Advancements here pave the way for development of a clinic-friendly OCT platform for monitoring glaucoma therapy.


Synchronization between Attractors: Genomic Mechanism of Cell-Fate Change.
Herein, we provide a brief overview of complex systems theory approaches to investigate the genomic mechanism of cell-fate changes. Cell trajectories across the epigenetic landscape, whether in development, environmental responses, or disease progression, are controlled by extensively coordinated genome-wide gene expression changes. The elucidation of the mechanisms underlying these coherent expression changes is of fundamental importance in cell biology and for paving the road to new therapeutic approaches. In previous studies, we pointed at dynamic criticality as a plausible characteristic of genome-wide transition dynamics guiding cell fate. Whole-genome expression develops an engine-like organization (genome engine) in order to establish an autonomous dynamical system, capable of both homeostasis and transition behaviors. A critical set of genes behaves as a critical point (CP) that serves as the organizing center of cell-fate change. When the system is pushed away from homeostasis, the state change that occurs at the CP makes local perturbation spread over the genome, demonstrating self-organized critical (SOC) control of genome expression. Oscillating-Mode genes (which normally keep genome expression on pace with microenvironment fluctuations), when in the presence of an effective perturbative stimulus, drive the dynamics of synchronization, and thus guide the cell-fate transition.


[Defects in autonomic regulation in myocardial ischemia].
To evaluate cerebral and peripheral mechanisms of autonomic regulation of the cardiovascular system, their role in development of myocardial ischemia in coronary heart disease (CHD) patients with coronary atherosclerosis and X syndrome. Psychometric testing, questionnaires, cardiovascular tests (by D. Y. Ewing), automatic spectral analysis of cardiac rhythm variability were used in investigation of psychovegetative regulation in 36 patients and 19 healthy subjects. Group 1 consisted of 26 CHD patients with coronary atherosclerosis and stable angina class I-II. Group 2 consisted of 10 patients with symptoms of myocardial ischemia and coronarographically intact coronary arteries. Patients of both groups demonstrated initial activation of cerebral sympathicoadrenal mechanisms manifesting with high anxiety, depression, vegetative defects in regulation of both initial autonomic tone and autonomic support of the orthostatic test. CHD patients with coronary atherosclerosis were characterized by persistent activation of cerebral sympathicoadrenal mechanisms and resistance of homeostatic baroreflex sympathetic systems. Vagal insufficiency was moderate and arose only at rest. In X syndrome patients with the same initial cerebral activation of the sympathicoadrenal mechanisms had dystonic trend in hemodynamic autonomic parameters: higher systolic blood pressure in subnormal heart rate, lability of baroreflex and cerebral mechanisms under the orthostatic test. The above features of psychovegetative relations make such patients very close to those with psychovegetative syndrome. CHD patients with coronary atherosclerosis and patients with X syndrome differ by mechanisms of maladaptation of autonomic regulation.


[The clinical effectiveness of the antiseptic treatment of the operative field for endoscopic adenotomy].
The objective of the present controlled randomized study was to estimate the clinical effectiveness of the antiseptic treatment of the operative field for endoscopic adenotomy. It is based on the results of the examination and treatment of 202 children at the age varying from 4 to 10 years admitted with the diagnosis of adenoids for the planned surgical intervention between 2010 and 2012. The results of the study indicate that postoperative objective and subjective symptoms of the disease were significantly less pronounced in the case of the preoperative treatment of the operative field than without it. Specifically, statistically significant reduction in the severity of postoperative reactive inflammation was documented. Double antiseptic washing of the nasopharynx caused neither complications nor undesirable adverse reactions and significantly reduced the requirements for systemic antibacterial preparations and anesthetics. It is concluded that the preoperative antiseptic treatment of the operative field for endoscopic adenotomy is a safe and effective procedure that can be recommended for a wider clinical application.


Effects of acute and chronic denervation on release of acetylcholinesterase and its molecular forms in rat diaphragms.
Hemidiaphragms were removed from rats at various times after intrathoracic transection of the left phrenic nerve and were incubated in organ baths containing 1.5 ml of oxygenated, buffered physiologic saline solution, with added glucose and bovine serum albumin. After incubation, the acetylcholinesterase (AChE: EC 126.96.36.199) activities of the bath fluid and of the muscle were determined. Innervated left hemidiaphragms were found to release 107 units of AChE over a 3-h period, corresponding to 1.9% of their total AChE activity. Denervation led to a rapid loss of AChE from the muscle coincident with a transient increase in the outpouring of enzyme activity into the bath fluid. Thus, 1 day after nerve transection the left hemidiaphragm contained only 68% of the control amounts of AChE activity, but released 140% as much as control. After 3 or 4 days of denervation, the AChE activity of the diaphragm stabilized at 35% of the control value. Release also fell below control by this time, but not as far. One week after denervation the release, 69 units per 3 hr, correspond to 3.3% of the reduced content of AChE activity in the muscle, indicating that denervation caused an increase in the proportion of AChE released. Sucrose density gradient ultracentrifugation showed that 10S AChE accounted for more than 80% of the released enzyme activity at all times. The results did not rule out the possibility, however, that the released enzyme originally stemmed from 4S or 16S AChE in the diaphragms.


Long-Term Results of Cortical Motor Stimulation for Neuropathic Peripheral and Central Pain: Real-World Evidence From Two Independent Centers.
Cortical motor stimulation (CMS) is used to modulate neuropathic pain. The literature supports its use; however, short follow-up studies might overestimate its real effect. This study brings real-world evidence from two independent centers about CMS methodology and its long-term outcomes. Patients with chronic refractory neuropathic pain were implanted with CMS. The International Classification of Headache Disorders 3rd Edition was used to classify craniofacial pain and the Douleur Neuropathique en 4 Questions Scale score to explore its neuropathic nature. Demographics and clinical and surgical data were collected. Pain intensity at 6, 12, and 24 months and last follow-up was registered. Numeric rating scale reduction of ≥50% was considered a good response. The Clinical Global Impression of Change scale was used to report patient satisfaction. Twelve males (38.7%) and 19 females (61.3%) with a mean age of 55.8 years (±11.9) were analyzed. Nineteen (61.5%) were diagnosed from painful trigeminal neuropathy (PTN), and seven (22.5%) from central poststroke pain. The mean follow-up was 51 months (±23). At 6 months, 42% (13/31) of the patients were responders, all of them being PTN (13/19; 68.4%). At last follow-up, only 35% (11/31) remained responders (11/19 PTN; 58%). At last follow-up, the global Numeric rating scale reduction was 34% (P = .0001). The Clinical Global Impression of Change scale punctuated 2.39 (±0.94) after 3 months from the surgery and 2.95 (±1.32) at last follow-up (P = .0079). Signs of suspicious placebo effect were appreciated in around 40% of the nonresponders. CMS might show long-term efficacy for neuropathic pain syndromes, with the effect on PTN being more robust in the long term. Multicentric clinical trials are needed to confirm the efficacy of this therapy for this and other conditions.


Stirring the strategic direction of scuba diving marine Citizen Science: A survey of active and potential participants.
Citizen Science (CS) strengthens the relationship between society and science through education and engagement, with win-win benefits. Marine Citizen Science (MCS) is increasingly popular, thanks to society's growing interest in marine environments and marine issues. Scuba diving significantly increases the potential of MCS, thanks to the skills and behavioural properties of people who participate in the sport. To be able to exploit this potential, however, MCS needs to face challenges related to CS, to scuba diving activities and to the broader scuba diving industry. In particular, engagement and recruitment of potential volunteers, as well as retention of active participants, represent key milestones. In order to reach these milestones, information is required on current participation levels of scuba divers in MCS, as well as the motivations behind participation, and the opinions held by potential participants in MCS. This study explored different case studies and methods of data collection to provide an overview of actual and potential participation in MCS by the scuba diving community. The results show that scuba divers, whether active or potential marine citizen scientists, are well disposed towards MCS. Some barriers, however, prevent the full participation of scuba divers as marine citizen scientists. Certain barriers extend beyond the control of both divers and MCS projects, while others, such as limited access to MCS projects and poor feedback after participation, can and should be addressed. The recommendations of this research provide strategic direction to MCS, so that the broad scuba diving community can be successfully integrated into MCS. These recommendations acknowledge the important role played by stakeholders in the scuba diving industry, as well as professional intermediaries and hired experts.


Effects of Fruit and Vegetable Consumption on Risk of Asthma, Wheezing and Immune Responses: A Systematic Review and Meta-Analysis.
Abstract: Evidence suggests that reduced intake of fruit and vegetables may play a critical role in the development of asthma and allergies. The present review aimed to summarize the evidence for the association between fruit and vegetable intake, risk of asthma/wheeze and immune responses. Databases including PubMed, Cochrane, CINAHL and EMBASE were searched up to June 2016. Studies that investigated the effects of fruit and vegetable intake on risk of asthma/wheeze and immune responses were considered eligible (n = 58). Studies used cross-sectional (n = 30), cohort (n = 13), case-control (n = 8) and experimental (n = 7) designs. Most of the studies (n = 30) reported beneficial associations of fruit and vegetable consumption with risk of asthma and/or respiratory function, while eight studies found no significant relationship. Some studies (n = 20) reported mixed results, as they found a negative association between fruit only or vegetable only, and asthma. In addition, the meta-analyses in both adults and children showed inverse associations between fruit intake and risk of prevalent wheeze and asthma severity (p < 0.05). Likewise, vegetable intake was negatively associated with risk of prevalent asthma (p < 0.05). Seven studies examined immune responses in relation to fruit and vegetable intake in asthma, with n = 6 showing a protective effect against either systemic or airway inflammation. Fruit and vegetable consumption appears to be protective against asthma.


Retrieval of information from long-term memory.
Information is represented in long-term memory as a network of associations among concepts. Information is retrieved by spreading activation from concepts in working memory through the network structure. The time required to retrieve information is a function of the level of activation that it achieves. Fanning of multiple paths from a node dissipates the activation the node sends down any path and increases retrieval time. Fan effects are reduced as subjects overlearn the material or when they can change their task from a recognition judgment to a consistency judgment.


Wine aging: a bottleneck story.
The sporadic oxidation of white wines remains an open question, making wine shelf life a subjective debate. Through a multidisciplinary synoptic approach performed as a remarkable case study on aged bottles of white wine, this work unraveled a yet unexplored route for uncontrolled oxidation. By combining sensory evaluation, chemical and metabolomics analyses of the wine, and investigating oxygen transfer through the bottleneck/stopper, this work elucidates the importance of the glass/cork interface. It shows unambiguously that the transfer of oxygen at the interface between the cork stopper and the glass bottleneck must be considered a potentially significant contributor to oxidation state during the bottle aging, leading to a notable modification of a wine's chemical signature.


Root system architecture analysis in Mesembryanthemum crystallinum (ice plant) seedlings reveals characteristic root halotropic response.
One of the major environmental stress factors that affect root growth is salinity. Arabidopsis thaliana, a glycophyte, shows halotropism, whereby it alters the direction of root growth in a non-gravitropic pattern to evade high soil salinity. Asymmetric auxin distribution regulated by the relocation of auxin-efflux carrier proteins is a key cellular event in the halotropic response. However, there are no reports of halotropism in halophytes. Here, we investigated root growth traits in Mesembryanthemum crystallinum (ice plant), under high salinity conditions. We hypothesized that ice plant roots would show halotropic responses different from those of Arabidopsis Notably, similar to halotropism observed in Arabidopsis, ice plant roots showed continuous root bending under salinity stress. However, the root elongation rate did not change in ice plants. Expression analyses of several genes revealed that auxin transport might be partially involved in ice plant halotropism. This study enhances our understanding of halophyte root adaptation to high salinity stress.


Design and solid phase synthesis of new DOTA conjugated (+)-biotin dimers planned to develop molecular weight-tuned avidin oligomers.
Chemical modifications of the biotin carrier in pretargeted avidin–biotin radionuclide therapy may be of paramount importance for tuning the amount of the radioactivity delivered to cancer cells by labelled biotins. We report here the synthesis of a collection of new synthetic DOTA-constructs bearing two (+)-biotin molecules (bis-biotins), designed for the creation of multimeric Av units (tetramers) bonded to the antibody. All the syntheses were carried out following the solid phase strategy and growing the molecules on a Rink Amide resin. The biotin heads are connected through spacers containing PEG or non-PEG residues. Molecular modelling calculations suggested that the Av cross-linking ability of the bis-biotins depends mainly on the spacers length, with the best results being expected for arms affording distances in the range of 10–25 Å between the biotin carboxylate atoms, in the fully extended conformation. SEC-HPLC MALLS analysis of the products of our Av/bis-biotin reaction mixtures have confirmed this hypothesis. The bis-biotin 16, where the non-PEG linker ensured a distance of 26.7 Å between the biotin moieties, gave about 50% of Av oligomers while the shorter analogue 18 (19.5 Å) afforded 100% of an Av polymer containing about 21 protein units. Remarkably, the solubility of both the bis-biotins, i.e.16 and 18, in aqueous solutions was good and they showed excellent stability against the action of peptidases.


NK cell-based cancer immunotherapy: from basic biology to clinical development.
Natural killer (NK) cell is a specialized immune effector cell type that plays a critical role in immune activation against abnormal cells. Different from events required for T cell activation, NK cell activation is governed by the interaction of NK receptors with target cells, independent of antigen processing and presentation. Due to relatively unsophisticated cues for activation, NK cell has gained significant attention in the field of cancer immunotherapy. Many efforts are emerging for developing and engineering NK cell-based cancer immunotherapy. In this review, we provide our current understandings of NK cell biology, ongoing pre-clinical and clinical development of NK cell-based therapies and discuss the progress, challenges, and future perspectives.


Variation in tissue outcome of ovine and human engineered heart valve constructs: relevance for tissue engineering.
Clinical application of tissue engineered heart valves requires precise control of the tissue culture process to predict tissue composition and mechanical properties prior to implantation, and to understand the variation in tissue outcome. To this end we investigated cellular phenotype and tissue properties of ovine (n = 8) and human (n = 7) tissue engineered heart valve constructs to quantify variations in tissue outcome within species, study the differences between species and determine possible indicators of tissue outcome. Tissue constructs consisted of polyglycolic acid/poly-4-hydroxybutyrate scaffolds, seeded with myofibroblasts obtained from the jugular vein (sheep) or the saphenous vein (from humans undergoing cardiac surgery) and cultured under static conditions. Prior to seeding, protein expression of α-smooth muscle actin, vimentin, nonmuscle myosin heavy chain and heat shock protein 47 were determined to identify differences at an early stage of the tissue engineering process. After 4 weeks of culture, tissue composition and mechanical properties were quantified as indicators of tissue outcome. After 4 weeks of tissue culture, tissue properties of all ovine constructs were comparable, while there was a larger variation in the properties of the human constructs, especially the elastic modulus and collagen content. In addition, ovine constructs differed in composition from the human constructs. An increased number of α-smooth muscle actin-positive cells before seeding was correlated with the collagen content in the engineered heart valve constructs. Moreover, tissue stiffness increased with increasing collagen content. The results suggest that the culture process of ovine tissues can be controlled, whereas the mechanical properties, and hence functionality, of tissues originating from human material are more difficult to control. On-line evaluation of tissue properties during culture or more early cellular markers to predict the properties of autologous tissues cultured for individual patients are, therefore, of utmost importance for future clinical application of autologous heart valve tissue engineering. As an example, this study shows that α-smooth muscle actin might be an indicator of tissue mechanical properties.


Growth Termination and Multiple Nucleation of Single-Wall Carbon Nanotubes Evidenced by in Situ Transmission Electron Microscopy.
In order to controllably grow single-wall carbon nanotubes (SWCNTs), a better understanding of the growth processes and how they are influenced by external parameters such as catalyst and gaseous environment is required. Here, we present direct evidence of growth termination of individual SWCNTs and successive growth of additional SWCNTs on Co catalyst particles supported on MgO by means of environmental transmission electron microscopy. Such in situ observations reveal the plethora of solid carbon formations at the local scale while it is happening and thereby elucidate the multitude of configurations resulting from identical external synthesis conditions, which should be considered in the quest for controlled SWCNT growth. Using CO and a mixture of CO and H2 as carbon sources, we show that the growth of SWCNTs terminates with a reduced tube-catalyst adhesion strength. Two main reasons for the cessation are proposed: insufficient active carbon species and a certain amount of stress exerted at the tube-catalyst interface. Interestingly, it was observed that catalyst particles stayed active in terms of nucleating additional solid carbon structures after growth termination of the first SWCNT. These observations elucidate the importance of an in-depth understanding of the role of catalysts and carbon sources in the continued growth of SWCNTs. Furthermore, it serves as a guide for further control of carbon nanostructure synthesis via catalyst engineering and synthesis optimization.


How to appropriately choose and arrange research factors.
Research factors are a very important element in any research design. Research factors include experimental and non-experimental factors. The former is the general term used to describe the similar experimental conditions that researchers are interested in, while the latter are other factors that researchers have little interest in but may influence the result. This article mainly focuses on the following issues: the definition of research factors, the selection and arrangement of experimental factors and non-experimental factors, the interaction between research factors, the standardization of research factors and the common mistakes frequently made by researchers.


Cathepsin B Is Dispensable for Cellular Processing of Cathepsin B-Cleavable Antibody-Drug Conjugates.
Antibody-drug conjugates (ADC) are designed to selectively bind to tumor antigens via the antibody and release their cytotoxic payload upon internalization. Controllable payload release through judicious design of the linker has been an early technological milestone. Here, we examine the effect of the protease-cleavable valine-citrulline [VC(S)] linker on ADC efficacy. The VC(S) linker was designed to be cleaved by cathepsin B, a lysosomal cysteine protease. Surprisingly, suppression of cathepsin B expression via CRISPR-Cas9 gene deletion or shRNA knockdown had no effect on the efficacy of ADCs with VC(S) linkers armed with a monomethyl auristatin E (MMAE) payload. Mass spectrometry studies of payload release suggested that other cysteine cathepsins can cleave the VC(S) linker. Also, ADCs with a nonprotease-cleavable enantiomer, the VC(R) isomer, mediated effective cell killing with a cysteine-VC(R)-MMAE catabolite generated by lysosomal catabolism. Based on these observations, we altered the payload to a pyrrolo[2,1-c][1,4]benzodiazepine dimer (PBD) conjugate that requires linker cleavage in order to bind its DNA target. Unlike the VC-MMAE ADCs, the VC(S)-PBD ADC is at least 20-fold more cytotoxic than the VC(R)-PBD ADC. Our findings reveal that the VC(S) linker has multiple paths to produce active catabolites and that antibody and intracellular targets are more critical to ADC efficacy. These results suggest that protease-cleavable linkers are unlikely to increase the therapeutic index of ADCs and that resistance based on linker processing is improbable. Cancer Res; 77(24); 7027-37. ©2017 AACR.


The influence of elbow joint kinematics on wrist speed in cricket fast bowling.
This modelling study sought to describe the relationships between elbow joint kinematics and wrist joint linear velocity in cricket fast bowlers, and to assess the sensitivity of wrist velocity to systematic manipulations of empirical joint kinematic profiles. A 12-camera Vicon motion analysis system operating at 250 Hz recorded the bowling actions of 12 high performance fast bowlers. Empirical elbow joint kinematic data were entered into a cricket bowling specific "Forward Kinematic Model" and then subsequently underwent fixed angle, angular offset and angle amplification manipulations. A combination of 20° flexion and 20° abduction at the elbow was shown to maximise wrist velocity within the experimental limits. An increased elbow flexion offset manipulation elicited an increase in wrist velocity. Amplification of elbow joint flexion-extension angular displacement indicated that, contrary to previous research, elbow extension range of motion and angular velocity at the time of ball release were negatively related to wrist velocity. Some relationships between manipulated joint angular waveforms and wrist velocity were non-linear, supporting the use of a model that accounts for the non-linear relationships between execution and outcome variables in assessing the relationships between elbow joint kinematics and wrist joint velocity in cricket fast bowlers.


The Psychometric Properties of the Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR) in Patients with HBV-Related Liver Disease.
Comorbid depression in Hepatitis B virus (HBV) is common. Developing accurate and time- efficient tools to measure depressive symptoms in HBV is important for research and clinical practice in China. This study tested the psychometric properties of the Chinese version of the 16-item Quick Inventory of Depressive Symptomatology (QIDS-SR) in HBV patients. The study recruited 245 depressed patients with HBV and related liver disease. The severity of depressive symptoms was assessed with the Montgomery-Asberg Depression Rating Scale (MADRS) and the QIDS-SR. Internal consistency (Cronbach's alpha) was 0.796 for QIDS-SR. The QIDS-SR total score was significantly correlated with the MADRS total score (r=0.698, p<0.001). The QIDS-SR showed unidimensional measurement properties in exploratory factor analysis. The QIDS-SR (Chinese version) has good psychometric properties in HBV patients and appears to be useful in assessing depression in clinical settings.


Hypergeometric-Gaussian modes.
We studied a novel family of paraxial laser beams forming an overcomplete yet nonorthogonal set of modes. These modes have a singular phase profile and are eigenfunctions of the photon orbital angular momentum. The intensity profile is characterized by a single brilliant ring with the singularity at its center, where the field amplitude vanishes. The complex amplitude is proportional to the degenerate (confluent) hypergeometric function, and therefore we term such beams hypergeometric-Gaussian (HyGG) modes. Unlike the recently introduced hypergeometric modes [Opt. Lett. 32, 742 (2007)], the HyGG modes carry a finite power and have been generated in this work with a liquid-crystal spatial light modulator. We briefly consider some subfamilies of the HyGG modes as the modified Bessel Gaussian modes, the modified exponential Gaussian modes, and the modified Laguerre-Gaussian modes.


Leisure-Time Physical Activity, Sedentary Behaviour and Diet Quality are Associated with Metabolic Syndrome Severity: The PREDIMED-Plus Study.
Healthy lifestyle factors, such as physical activity (PA) and Mediterranean diet (MD), decrease the likelihood of developing metabolic syndrome (MetS). The aim of this study was to report main lifestyle components and related factors according to the MetS severity. Cross-sectional analysis was done of baseline lifestyle factors from 5739 participants with overweight/obesity and MetS features (aged 55-75 years) included in the PREDIMED-PLUS primary cardiovascular prevention randomized trial. Participants were categorized in tertiles according to a validated MetS severity score (MetSSS). Anthropometrics, visceral adiposity index, dietary nutrient intake, biochemical marker levels, as well as a Dietary Inflammatory Index and depression symptoms (Beck Depression Inventory-II) were measured. Diet quality was assessed using a 17-item energy-restricted MD questionnaire. Duration and intensity of PA was self-reported using the Minnesota-REGICOR Short Physical Activity Questionnaire. Sedentary behaviours were measured using the Spanish version of the Nurses' Health Study questionnaire. The 30 s chair stand test was also assessed. Participants with highest MetSSS showed higher values of cardiovascular risk factors (except for total cholesterol and LDL cholesterol), depression risk, sedentary and TV viewing time, and lower moderate and vigorous leisure-time physical activity (LTPA). Highest MetSSS participants tended to a pro-inflammatory dietary pattern and tended to lower MD adherence. In addition, they showed lower carbohydrate and nut intake and higher intake of protein, saturated and trans fatty acids, cholesterol, iodine, sodium, red and processed meat products, other oils different from olive oil and spirit alcoholic drinks. The highest MetS severity score was associated with lower moderate and vigorous LTPA and higher sedentary time and depression risk, as they tended to a pro-inflammatory dietary pattern and lower MD adherence.


Homozygous feature of isolated triphalangeal thumb-preaxial polydactyly linked to 7q36: no phenotypic difference between homozygotes and heterozygotes.
Preaxial polydactyly is a common limb malformation in humans with variable clinical expression. Different types of triphalangeal thumb-preaxial polydactyly phenotypes were mapped to the chromosome 7q36 region. We studied a large Turkish family of 69 individuals, of whom 22 individuals were affected. In all, 11 affected family members were clinically and radiologically evaluated. All affected individuals had a triphalangeal thumb and a preaxial (hypoplastic) extra digit bilaterally, with minimal intrafamilial variation. No feet involvement was observed. Linkage and haplotype analyses using 20 informative meioses confirmed the 7q36 region contained the LIMBR1 gene. Maximum logarithm of the odds (LOD) scores were obtained with DNA markers D7S550 and D7S2423. We have further identified a novel C to T alteration at position 4909 bp in the critical zone of polarizing activity regulatory sequence (ZRS) region, in the intron 5, of the LMBR1 gene. One affected male with homozygous status and no phenotypic difference from affected family members with heterozygous status represented the first homozygote case of the triphalangeal thumb-preaxial polydactyly phenotype.


Program evaluation of an Integrated Basic Science Medical Curriculum in Shiraz Medical School, Using CIPP Evaluation Model.
In recent years curriculum reform and integration was done in many medical schools. The integrated curriculum is a popular concept all over the world. In Shiraz medical school, the reform was initiated by stablishing the horizontal basic science integration model and Early Clinical Exposure (ECE) for undergraduate medical education. The purpose of this study was to provide the required data for the program evaluation of this curriculum for undergraduate medical students, using CIPP program evaluation model. This study is an analytic descriptive and triangulation mixed method study which was carried out in Shiraz Medical School in 2012, based on the views of professors of basic sciences courses and first and second year medical students. The study evaluated the quality of the relationship between basic sciences and clinical courses and the method of presenting such courses based on the Context, Input, Process and Product (CIPP) model. The tools for collecting data, both quantitatively and qualitatively, were some questionnaires, content analysis of portfolios, semi- structured interview and brain storming sessions. For quantitative data analysis, SPSS software, version 14, was used. In the context evaluation by modified DREEM questionnaire, 77.75%of the students believed that this educational system encourages them to actively participate in classes. Course schedule and atmosphere of class were reported suitable by 87.81% and 83.86% of students. In input domain that was measured by a researcher made questionnaire, the facilities for education were acceptable except for shortage of cadavers. In process evaluation, the quality of integrated modules presentation and Early Clinical Exposure (ECE) was good from the students' viewpoint. In product evaluation, students' brain storming, students' portfolio and semi-structured interview with faculties were done, showing some positive aspects of integration and some areas that need improvement. The main advantage of assessing an educational program based on CIPP evaluation model is that the context, input, process and product of the program are viewed and evaluated systematically. This will help the educational authorities to make proper decisions based on the weaknesses and strengths of the program on its continuation, cessation and revision. Based on the results of this study, the integrated basic sciences course for undergraduate medical students in Shiraz Medical School is at a desirable level. However, attempts to improve or reform some sections and continual evaluation of the program and its accreditation seem to be necessary.


Implantation of Brain-Derived Extracellular Matrix Enhances Neurological Recovery after Traumatic Brain Injury.
Scaffolds composed of extracellular matrix (ECM) are being investigated for their ability to facilitate brain tissue remodeling and repair following injury. The present study tested the hypothesis that the implantation of brain-derived ECM would attenuate experimental traumatic brain injury (TBI) and explored potential underlying mechanisms. TBI was induced in mice by a controlled cortical impact (CCI). ECM was isolated from normal porcine brain tissue by decellularization methods, prepared as a hydrogel, and injected into the ipsilesional corpus callosum and striatum 1 h after CCI. Lesion volume and neurological function were evaluated up to 35 d after TBI. Immunohistochemistry was performed to assess post-TBI white matter integrity, reactive astrogliosis, and microglial activation. We found that ECM treatment reduced lesion volume and improved neurobehavioral function. ECM-treated mice showed less post-TBI neurodegeneration in the hippocampus and less white matter injury than control, vehicle-treated mice. Furthermore, ECM ameliorated TBI-induced gliosis and microglial pro-inflammatory responses, thereby providing a favorable microenvironment for tissue repair. Our study indicates that brain ECM hydrogel implantation improved the brain microenvironment that facilitates post-TBI tissue recovery. Brain ECM offers excellent biocompatibility and holds potential as a therapeutic agent for TBI, alone or in combination with other treatments.


A hybrid deep transfer learning model with machine learning methods for face mask detection in the era of the COVID-19 pandemic.
The coronavirus COVID-19 pandemic is causing a global health crisis. One of the effective protection methods is wearing a face mask in public areas according to the World Health Organization (WHO). In this paper, a hybrid model using deep and classical machine learning for face mask detection will be presented. The proposed model consists of two components. The first component is designed for feature extraction using Resnet50. While the second component is designed for the classification process of face masks using decision trees, Support Vector Machine (SVM), and ensemble algorithm. Three face masked datasets have been selected for investigation. The Three datasets are the Real-World Masked Face Dataset (RMFD), the Simulated Masked Face Dataset (SMFD), and the Labeled Faces in the Wild (LFW). The SVM classifier achieved 99.64% testing accuracy in RMFD. In SMFD, it achieved 99.49%, while in LFW, it achieved 100% testing accuracy.


Induction of the synthesis of a specific protein in rat submandibular gland by isoproterenol.
Prolonged treatment of rats with the beta-adrenergic agonist, isoproterenol (IPR), produces hypertrophy and hyperplasia of the parotid and submandibular glands. The drug induces the synthesis of several secretory proteins that are absent or occur at very low concentrations in the gland or saliva of the untreated rat. We have measured the relative concentrations of one of these proteins (termed "large mobile" (LM) protein, Menaker et al. (1974) Lab. Invest. 30, 341-349) by using a solid phase enzyme-linked immunoabsorption assay. LM protein was not measurable in gland extracts of 20-day-old fetuses or 2-day-old rats. Its concentration was very low in the glands of 6- and 13-day-old and adult rats. Administration of IPR for 4 to 7 days to adult or 6-day old rats increased the levels of the LM protein by 20 to 25-fold. The LM protein was localized immunocytochemically primarily in the acinar cells in the glands of control and IPR-treated adult rats. In vitro translation studies using a mRNA-dependent reticulocyte lysate system and labeling with [35S]methionine showed: little synthesis of pro-LM from poly(A+) RNA from glands of adult rats and none from 13-day-old animals, and that, in comparison, poly(A+) RNA from glands of adult or 13-day-old IPR-treated rats directed the synthesis of a much greater concentration of pro-LM. The in vitro precursor of the LM protein migrated electrophoretically as a single band in anti-LM immunoprecipitates, and had a molecular weight of 14,000. The LM protein, which appears to be a single, unique polypeptide induced by IPR in the submandibular glands of developing and adult rats, will be useful in studies examining the effects of catecholamine beta-agonists on gene expression in an exocrine cell.


[Effect of trypsin-like enzyme inhibitor on certain metabolic processes in the acute period of experimental myocardial ischemia].
The effect of trasylol upon the activeness of proteolysis in the cytoplasm and mitochondrial-lysosomal fractions of the heart muscle was studied in the acute experimental period of myocardial ischaemia (5 days) along with a determination of the spectrum of the iso-enzymes of the lactate- and malate- dehydrogenases. For the evaluation of oxidation processes in vitro the iections. Trasylol was found to limit the proteolysis in the cytostructures of the myocardium cell, to increase the activity of the transaminases, as well as to help the normalization of thespectrum of the NAD-dependent iso-enzymes. At the same time, under the effect of the employed drug, the myocardial consumption of the radioactive carbon from the acetate Na-2C-14 increases.


CO2 deficit in temperate forest soils receiving high atmospheric N-deposition.
Evidence is provided for an internal CO2 sink in forest soils, that may have a potential impact on the global CO2-budget. Lowered CO2 fraction in the soil atmosphere, and thus lowered CO2 release to the aboveground atmosphere, is indicated in high N-deposition areas. Also at forest edges, especially of spruce forest, where additional N-deposition has occurred, the soil CO2 is lowered, and the gradient increases into the closed forest. Over the last three decades the capacity of the forest soil to maintain the internal sink process has been limited to a cumulative supply of approximately 1000 and 1500 kg N ha(-1). Beyond this limit the internal soil CO2 sink becomes an additional CO2 source, together with nitrogen leaching. This stage of "nitrogen saturation" is still uncommon in closed forests in southern Scandinavia, however, it occurs in exposed forest edges which receive high atmospheric N-deposition. The soil CO2 gradient, which originally increases from the edge towards the closed forest, becomes reversed.


Hypertonic HBOC-201 decreases neutrophil activation after hemorrhagic shock.
To evaluate neutrophil activation after exposure to standard HBC-201 (suspended in lactate Ringer's solution) versus HBOC-201 suspended in hypertonic 7.5% saline solution. We use plasma and tissue obtained from pigs subjected to controlled hemorrhagic shock and an ex vivo model of stimulated human whole blood. The pigs were resuscitated with the following (n = 8 per group) standard HBOC-201, or hypertonic HBOC-201. We used HTS 7.5%, Ringer's lactate as control resuscitation. Human blood was stimulated with same fluids. We measured the following neutrophil markers; IL-8, H2O2 in pig plasma, MPO in pig tissue, and H2O2, IL-8, and CD11b/CD18 in human whole blood. H2O2 and IL-8 as well as tissue MPO were significantly decreased in pigs resuscitated with HT-HBOC-201 and HT 7.5%. Ex vivo experiments blood diluted with HTS and HT-HBOC-201 revealed lower expression of CD11b/CD18, H2O2, and IL-8. Blood diluted with HBOC-201 had a higher CD11b/CD18 expression than blood diluted with LR solution. Our in vivo and ex vivo experiments indicate that HBOC-201 suspended in hypertonic 7.5% saline solution is associated with significantly less neutrophil activation when compared to standard HBOC-201 suspended in lactate Ringer's solution.


Arm-free paraplegic standing--Part I: Control model synthesis and simulation.
The following paper is the first part of our investigation into the feasibility of arm-free paraplegic standing. A novel control strategy for unsupported paraplegic standing which utilizes the residual sensory and motor abilities of the thoracic spinal cord injured subjects is proposed. The strategy is based on voluntary and reflex activity of the paraplegic person's upper body and artificially controlled stiffness in the ankles. The knees and hips are maintained in an extended position by functional electrical stimulation (FES). The analysis of a linearized double inverted pendulum model revealed that with properly selected ankle stiffness the system can be easily stabilized. We developed a closed-loop double inverted pendulum model including a neural system delay, trunk muscles dynamics, body segmental dynamics and linear quadratic regulator (LQR) optimal controller. Through simulations of the closed-loop model two different strategies for disturbance rejection were explained. We investigated the capability of the closed-loop model to reject disturbances, imposed at the ankle joint (in anterior and posterior directions) for various stiffness levels and neural system delays in the presence of biomechanical constraints. By limiting permissible excursions of the center of pressure, we found out that the length of the foot is the most important constraint, while the strength of the trunk muscles is not of major importance for successful balancing. An ankle stiffness of approximately 10 Nm/degree suffices for arm-free standing of paraplegic subjects.


[The bladder catheter].
The benefit of the transurethral catheter to protect or measure renal function is well accepted. Urethral stricture and infection of the lower urinary tract as the complications should lead to a cautious use of catheters. A careful placement, the choice of the best material and a correct management help to avoid complications. Alternatives are discussed.


Long-term Treatment Response and Patient Outcomes for Vestibular Schwannoma Patients Treated with Hypofractionated Stereotactic Radiotherapy.
The aim of this study is to evaluate long-term treatment outcome and toxicities among vestibular schwannoma (VS) patients treated with hypofractionated stereotactic radiotherapy (HSRT). 383 patients with unilateral VS treated with HSRT (25 Gy, five fractions) between 1995 and 2007 were retrospectively reviewed. Treatment failure was defined as requiring salvage microsurgery. Posttreatment new/progressive clinical symptoms or increases in baseline tumor volume (BTV) due to treatment effect or progression were noted. Symptom outcomes were reported as baseline and posttreatment ± improvement, respectively. Symptoms were grouped by cranial nerve (CN) VII or CNVIII. Audiometry was assessed baseline and posttreatment hearing. Patients were grouped as having greater than serviceable hearing [Gardner Robertson (GR) score 1-2] or less than non-serviceable hearing (GR score 3-5) by audiometry. Median follow-up was 72.0 months. Nine (2.3%) experienced treatment failure. At last follow-up, 74 (19.3%) had new/progressive symptoms and were categorized as radiologic non-responders, whereas 300 (78.3%) had no tumor progression and were grouped as radiologic responders. Average pretreatment BTV for treatment failures, radiologic non-responders, and radiologic responders was 2.11, 0.44, and 1.87 cm3, respectively. Pretreatment CNVII and CNVIII symptoms were present in 9.4 and 93.4% of patients, respectively. Eight (24%) with pre-HSRT CNVII and 37 (10%) with pre-HSRT CNVIII symptoms recovered CN function post-HSRT. Thirty-five (9%) and 36 (9.4%) experienced new CNVII and CNVIII deficit, respectively, after HSRT. Of these, 20 (57%) and 18 (50%) recovered CNVII and CNVIII function, respectively, after HSRT. Evaluable audiograms were available in 199 patients. At baseline and at last follow-up, 65.8 and 36.2% had serviceable hearing, respectively. Fifty-one percent had preservation of serviceable hearing at last follow-up. Treatment of VS with HSRT is effective with treatment success in 97.7% and an acceptable toxicity profile. Less than one-third of patients experience any new CNVII or CNVIII deficit posttreatment. Greater than 50% of patients with serviceable hearing at baseline maintained hearing function. Improved methods to differentiate treatment effect and tumor progression are needed.


Working Collaboratively: Outcomes of Geriatrician Input in Older Patients Undergoing Emergency Laparotomy in a District General Hospital.
With the increasing median age of survival in the UK, there is an increased burden on the provision of medical and surgical care to the population. The 2010 National Confidential Enquiry into Patient Outcome and Death report, "An Age Old Problem," emphasizes the early involvement of surgical and geriatric consultant input to improve perioperative care in older patients. This study describes the development of a Geriatric Surgical Liaison Service aimed at providing consultant-led geriatrician support to improve the outcomes of older patients undergoing Emergency Laparotomy (EL). The primary outcome is the reduction in length of stay (LOS) compared to baseline data prior to geriatrician involvement. The service was designed to include one clinical session involving a consultant geriatrician and two and a half days with a junior doctor in a week. Data was collected prospectively from February 2018 till July 2018 for surgical patients aged ≥ 70 years, who underwent EL, had an inpatient stay of more than seven days, and who were diagnosed with delirium or incurred inpatient falls (intervention group). Baseline data, prior to geriatrician involvement, were collected retrospectively for EL patients aged ≥ 70 years from December 2015 until May 2016. Length of stay and 30-day mortality were also compared between the two cohorts undergoing EL. A total of 69 patients were included in the intervention group; 45 patients underwent EL and their mean LOS was 17.5 days, which was reduced from 22.5 days prior to geriatrician involvement (n=57). There was no difference in median length of stay and 30-day mortality between the retrospective baseline group and the intervention groups. In the intervention group, 8.5% of patients had a new medical diagnosis and 26.8% of patients were offered follow-ups. Although statistically not significant (p=0.40), a shorter stay in hospital by five days can potentially have a positive impact on patient outcomes by reducing psychosocial, cognitive, and functional deconditioning. This would also improve patient flow, release capacity, and waiting times and would be of benefit to the financially strained National Health Service (NHS). Overall, our study suggests that a collaborative, consultant-led geriatric service can improve the management of older surgical patients by potentially reducing length of stay, identifying high-risk patients, and facilitating early and appropriate specialty input alongside adequate and required outpatient follow-up.


Evaluation of agricultural reuse practices and relevant guidelines for the alba rancho WWTP (primary and secondary facultative ponds) in Cochabamba, Bolivia.
Many cities in developing countries are experiencing high population growth, which is generating chaotic and unplanned development, reducing land areas available for agriculture, and polluting surface and groundwater. Consequently, the reuse of untreated or partially treated wastewater for agricultural irrigation is increasing in arid and semi-arid regions in developing countries. Cochabamba city in Bolivia also has a high population growth. The climatic characteristics and the lack of clean water sources in this city are forcing the agriculture sector to use treated and untreated wastewater for irrigation. We investigated the effluent quality of the Alba Rancho Wastewater Treatment Plant (WWTP) in Cochabamba, Bolivia, and the existing effluent reuse practices for irrigation of fodder crops in the surrounding agricultural land (La Mayca area). The plant uses primary and secondary facultative ponds, and does not achieve the required effluent quality (according to Bolivian environmental law) for effluent BOD, COD, TDS and faecal coliforms. This paper also includes a brief comparison of guidelines for wastewater reuse in agriculture from several developing and developed countries, comparing the parameters measured as pollution indicators. It appears that for developed countries, the main concern is the health risk that reuse can cause to the farmers and consumers. For developing countries on the other hand, pollution reduction is currently the major aim in their guidelines and standards.


PRODUCTION OF ELASTASE AND PROTEINASE BY PSEUDOMONAS AERUGINOSA.
Morihara, Kazuyuki (Shionogi Research Laboratory, Osaka, Japan). Production of elastase and proteinase by Pseudomonas aeruginosa. J. Bacteriol. 88:745-757. 1964.-Some strains of Pseudomonas aeruginosa produced elastase, but the others did not. The elastase-positive strains produced two proteinases (fractions II and III), and the elastase-negative strains produced one proteinase (fraction III). Moreover, one proteinase (fraction I) was produced by both elastase-positive and elastase-negative strains, but the activity was small and negligible. The three proteinases were separated by column chromatography on diethylaminoethyl-cellulose, and elastolytic activity corresponded to fraction II. The effect of components of the medium was slight for production of fraction II; fraction III was produced only in synthetic medium containing Ca ion and not in natural medium. The optimal pH of fractions I, II, and III for casein was 6.5, 8.0, and 10.0, respectively; that of fraction II for elastin was 7.5 to 8.0. The other characters of the three proteinases also differed. Both the proteolytic and the elastolytic activities of fraction II showed a similar behavior for various treatments, except the inhibition test by NaCl and serum. Fraction III proteinases from various strains were identical in their enzymatic or other characters, showing that various strains were related regardless of the difference of their elastolytic activity. The reason that the elastolytic activity of P. aeruginosa differed according to the origin of the strain is discussed on the basis of a taxonomic study; results indicate that the ability to produce elastolytic activity (fraction II) may be a dissociative character of the species.


Safety and immunogenicity of HIV recombinant envelope vaccines in HIV-infected infants and children. National Institutes of Health-sponsored Pediatric AIDS Clinical Trials Group (ACTG-218).
Study objectives were to evaluate the safety and immunogenicity of three HIV recombinant glycoproteins in HIV-infected infants and children between 1 month and 18 years of age with asymptomatic (P-1) infection. Using Chiron rgp 120 (SF-2) 15 or 50 microg; MicroGeneSys rgp 160 (IIIB) 40 or 320 microg; Genentech rgp120 (MN) 75 or 300 microg; or adjuvant control (Alum or MF-59), children were randomized to a double-blind, placebo-controlled, dose-escalating study of vaccine administered intramuscularly at entry and 1, 2, 3, 4, and 6 months later. No adverse events were attributed to study vaccines. Between 30% and 56% of volunteers exhibited a lymphoproliferative response as defined in terms of stimulation index (SI) to vaccine antigens; 65% of vaccinees but none of placebo recipients exhibited moderate or strong responses after enzyme immunoassay to HIV specific antigens. CD4 cell counts and quantitative HIV culture did not differ significantly among vaccine and control groups, nor were differences found among groups in HIV disease progression. The rgp160 and gp120 subunit vaccines were safe and immunogenic in this population.


Fungicides chlorothanolin, azoxystrobin and folpet induce transcriptional alterations in genes encoding enzymes involved in oxidative phosphorylation and metabolism in honey bees (Apis mellifera) at sublethal concentrations.
Fungicides are highly used for plant protection but their molecular and chronic effects are poorly known. Here, we analyse transcriptional effects in the brain of honey bees of three frequently applied fungicides, azoxystrobin, chlorothanolin and folpet, after oral exposure for 24, 48 and 72 h. Among transcripts assessed were genes encoding proteins for immune and hormone system regulation, oxidative phosphorylation, metabolism, and acetylcholine receptor alpha 1. Azoxystrobin and folpet induced minor alterations, including down-regulation of hbg-3 by azoxystrobin and induction of ndufb-7 by folpet. Chlorothanolin induced strong transcriptional down-regulation of genes encoding enzymes related to oxidative phosphorylation and metabolism, including cyp9q1, cyp9q2 and cyp9q3, acetylcholine receptor alpha 1 and hbg-3 and ilp-1, which are linked to hormonal regulation and behavioural transition of honey bees. Exposures to chlorothanolin in different seasonal times showed different responsiveness; responses were faster and often stronger in April than in June. Chlorothanolin caused the strongest effects and affected transcriptional abundance of genes related to energy production, metabolism and the endocrine system. Disturbed energy production may reduce foraging activity and hormonal dysregulation, such as the transition of nurse bees to foragers. Further analyses are needed to further substantiate potential adverse effects of chlorothanolin in bees on the physiological level.


Moving toward targeted eating disorder care for transgender, non-binary, and gender expansive patients in the United States.
Literature suggests that transgender, non-binary, and/or gender expansive (TNG) people are more likely than cisgender peers to experience eating disorders (EDs) and engage in dangerous weight control behaviors. TNG individuals with EDs are dramatically higher risk for self-harm behaviors, suicidal ideation, and suicidal behaviors than cisgender peers with EDs or TNG peers without EDs, and often engage in ED symptoms/behaviors to alleviate gender dysphoria. Yet, no treatment paradigms have yet been adapted for TNG-specific ED care. This qualitative study aims to identify stakeholder needs from such care to inform future clinical interventions. We elicited patient (n = 12) and mental health clinician (n = 9) stakeholder needs and preferences regarding TNG-specific ED care. Semi-structured interview guides informed by the Consolidated Framework for Implementation Research (CFIR) and a behavioral insights framework, EAST, were developed to ensure uniform inclusion and sequencing of topics and allow for valid comparison across interviews. Using a rapid analysis procedure, we produced a descriptive analysis for each group identifying challenges of and opportunities in providing ED care for TNG adults. Stakeholders expressed needs and preferences for TNG-specific treatment including that it be: (1) TNG-affirming, weight-inclusive, trauma-informed, and anti-racist; (2) delivered by an interdisciplinary team, including gender-affirming care clinicians; (3) focused on parsing gender dysphoria from other body image concerns, building distress tolerance, and working toward gender euphoria (rather than body acceptance). Future work is needed exploring ED care delivery models that integrate gender-affirming care services with mental health care. Such models may improve TNG access to ED treatment and recovery. Transgender, non-binary, and/or gender expansive (TNG) experience disproportionately high rates of eating disorders and have unique barriers to accessing care. In individual interviews, TNG adults with eating disorders and mental health clinicians who provide psychotherapy for eating disorders voiced desire for greater availability of TNG-affirming, weight-inclusive eating disorder care, integrated with other gender-affirming care services. This informs future research developing eating disorder care for TNG individuals.


Gabexate and camostat, synthetic proteinase inhibitors, as direct inducing factors of water and bicarbonate secretion in the isolated and blood-perfused dog pancreas.
The effects of proteinase inhibitors on the secretion of pancreatic juice were investigated in preparations of the isolated and blood-perfused dog pancreas as compared with those of secretin. Each drug tested was administered i.a. Graded doses of gabexate (1-10 mg) elicited dose-dependent biphasic responses for the secretory rates, bicarbonate concentrations and outputs of pancreatic juice, with maximum effects at approximately 5 mg, but had little effect on the protein concentrations. Camostat, at a high dose of 10 mg, caused significant increases in the secretory rate, bicarbonate concentration and output of pancreatic juice over their basal levels, but had little influence on the protein concentration. Secretin (0.03-0.3 U) usually produced similar to gabexate-induced results (1-5 mg). Both bicarbonate and protein concentrations of the juice obtained with gabexate or camostat were almost the same as those obtained with secretin at a similar secretory rate of pancreatic juice, suggesting the secretory action of gabexate or camostat might be similar to that of secretin. In addition, gabexate (3 mg) and camostat (10 mg) elicited more than the respective additive secretory responses in the presence of i.a. infusion of a phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine (12 micrograms/min) as well as secretin (0.1 U). These results indicate that gabexate and camostat induce water and bicarbonate secretion by acting directly on ductular cells of the dog pancreas, which might be mediated at least partially through cyclic AMP.