Allergen Immunotherapy: Vaccine Modification.
There is a need for newer therapeutic agents that improve the safety of allergen immunotherapy, provide ease of delivery to patients that fosters compliance and allows access to a greater proportion of the allergic population who could benefit from this disease-modifying treatment, and achieve an acceptable therapeutic benefit for patients committing to the treatment. The advances in sublingual allergen immunotherapy are encouraging, as this offers patients a noninjectable form of treatment of inhalant allergies. The continued research and development of the novel therapeutic constructs discussed in this article holds the promise of accomplishing the aforementioned goals in the future.


Pseudodiverticula of ureter: radiologic and histologic findings.
A 70-year-old man with previous history of TUR-BT presented positive urinary cytology at one year follow-up. Cystoscopy with bladder mapping was negative, and IVP revealed multiple outpouchings of the right upper ureter without hydronephrosis. Ureteroscopy failed because of an underlying stricture. Surgical excision of the strictured segment and of 2.5 cm of cranial ureter was performed. Histopathology demonstrated focal hyperplasia of the urothelium with outpouchings involving only the mucosa, compatible with the diagnosis of pseudodiverticula.


Interdisciplinary simulation scenario in nursing education: Humanized childbirth and birth.
to develop and validate with a panel of experts a scenario of maternal-child clinical simulation, related to humanized childbirth and birth. methodological study based on the Jeffries framework and standardized guides of the International Nursing Association for Clinical Simulation in Learning, which used analysis with descriptive statistics for general aspects of adherence to the aforementioned guide and inferential statistics for validating the checklist of actions through the Intraclass Correlation Coefficient (ICC). the scenario contains learning objectives, necessary resources, prebriefing and debriefing of guidelines, description of the simulated situation, participants and roles, and checklist of expected actions. The validation obtained an agreement level above 80% in all aspects evaluated by 31 experts, highlighting realism of the environment and setting, vital sign parameters, alignment with scientific literature and encouragement of critical thinking and problem solving. In addition, the checklist of actions was validated with 0.899 agreement among experts, statistically analyzed by the ICC and Cronbach's alpha 0.908 (95% confidence interval). the simulated scenario on humanized childbirth and birth can strengthen the articulation between women's and children's health disciplines, and was validated by experts.


On potassium functional feedback in neuromuscular junction.
The dependence of the reversal potential (Erev) of intracellular end-plate potentials (epp) on activity patterns was studied in frog neuromuscular preparations. A shift of Erev to the positive side was found with change in frequency of stimulation from 1/sec to 50/sec. This shift corresponds to the increase of potassium concentration in the synaptic cleft to 7.0 mM. The effect of potassium concentration [K+]0 in the bath solution on quantal content (m) of epp was studied. The quantity m increased when [K+]0 was varied within the range 4.7-8.7 mM; m decreased when [K+]0 was greater than 8.7 mM. Such a relationship between m and [K+]0 is accounted for by the combined effect of potassium on transmitter secretion and electrogenic processes in motor nerve terminals. The correlation between the change of m with [K+]0 and initial epp amplitudes was found and was attributed to potassium efflux from post-synaptic region in varying quantity depending on the initial epp amplitudes. A scheme of synaptic self-regulation by means of potassium feedback is suggested.


A Portable Hip Arthroscopy Simulator Demonstrates Good Face and Content Validity with Incomplete Construct Validity.
We evaluate the face, content, and construct validity of a portable hip arthroscopy module in a regional orthopaedic unit. Participants were recruited from a regional orthopaedic centre, and categorized into novice (0 arthroscopies), intermediate (1-29 arthroscopies), and expert (>50 arthroscopies) groups based on reported experience in arthroscopy. Face and content validity was evaluated by feedback from users immediately following completion of modules. Objective measurements, including time taken and subjective measurements consisting of simulation software metrics including, cam lesion locations attempts, scope strikes on bone, healthy bone burred, and cam lesion burred. Scores achieved by experts were recorded, and the median score was set at the level at which proficiency was demonstrated. Participant feedback on perceived educational use was collected following completion. In total, 20 participant results were included for analysis. Good face and content validity was expressed by participants with previous arthroscopic experience. Number of scope strikes within the simulator-derived metrics accurately discerned between levels of experience. Novices had a mean of 5 strikes per attempt (SD ± 5 ) , intermediates a mean of 5.8 strikes (SD ± 4.1). There was a significant difference between expert and novice groups (P = .01), and expert and intermediate groups (P = .002). No significant difference between overall performance scores achieved by participants in expert, intermediate, and novice groups (62% ± 19 vs 55% ± 22 vs 50% ± 23 , P = .15). This demonstrates incomplete construct validity of the simulator software-derived metrics. This hip arthroscopy simulator demonstrated acceptable face and content validity, with incomplete construct validity of simulator software metrics. Participants reported high levels of satisfaction with the module, highlighting that the addition of haptic feedback would be beneficial to improve procedural steps. Incorporation of tactile feedback to the modulator components would likely enable the software to accurately delineate between levels of experience. This study demonstrates good face and content validity. The addition of haptic feedback in a hip arthroscopy simulator may improve learning.


Hemodynamic benefits of matrix metalloproteinase-9 inhibition by doxycycline during experimental acute pulmonary embolism.
The authors examined whether acute pulmonary embolism (APE) increases lung matrix metalloproteinase (MMP)-2 and MMP-9 activities and whether inhibition of MMPs with doxycycline attenuates the hemodynamic changes associated with APE. Anesthetized male Wistar rats were monitored for mean arterial blood pressure (MAP) and heart rate (HR). Rats in the control group (n = 5) received only saline IV; rats in the embolism (Emb) group (n = 8) received saline IV followed 10 minutes later by an injection of Sephadex microspheres (9 mg/kg) IV; rats in the doxycycline (Doxy) group (n = 4) received only doxycycline (30 mg/kg) IV, followed 10 minutes later by an injection of saline IV; rats in the Doxy + Emb group (n = 8) received the same dose of doxycycline followed 10 minutes later by the same amount of microspheres described above. Lung samples were homogenized and assayed by SDS-polyacrilamide gel electrophoresis gelatin zymography to evaluate lung MMP-2 and MMP-9 activities. Saline or doxycycline produced no significant changes in MAP, HR, and in MMP-2 and MMP-9 activities. Conversely, lung embolization significantly reduced MAP by > 32 mm Hg and HR by > 90 bpm for more than 60 minutes, and increased MMP-9 activity by 43% (all p < 0.05). No significant differences were observed in MMP-2 activity. However, lung embolization produced only transient hypotension in rats pretreated with doxycycline. In this group, MAP returned to baseline values 5 to 10 minutes after embolization. In addition, pretreatment with doxycycline blunted the increase in lung MMP-9 activity after lung embolization (p < 0.05). This study demonstrates for the first time that MMP-9 inhibition with doxycycline attenuates APE-induced hemodynamic changes in the animal model examined. These findings indicate that MMP-9 activation plays a role in the pathophysiology of APE and suggest that pharmacologic strategies targeting specific MMPs with selective inhibitors may prevent the detrimental acute hemodynamic consequences of APE.


Modification of a guinea-pig hopper to reduce food wastage.
Food utilization in relation to gain in bodyweight was reduced by 18% without significantly affecting the growth of male guinea-pigs.


Measurement characteristics and clinical utility of the Brief Pain Inventory-Short Form for individuals with multiple sclerosis.
This Rehabilitation Measures Database summary provides a review of the psychometric properties of the BPI in individuals with MS. A full review of the BPI as well as reviews of over 330 other instruments can be found at www.rehabmeasures.org.


Statin-induced autoimmune myositis: a proposal of an "experience-based" diagnostic algorithm from the analysis of 69 patients.
Statin-induced autoimmune myositis (SIAM) represents a rare clinical entity that can be triggered by prolonged statin treatment. Its pathogenetic substrate consists of an autoimmune-mediated mechanism, evidenced by the detection of antibodies directed against the 3-hydroxy-3-methylglutaryl-coenzyme A reductase (anti-HMGCR Ab), the target enzyme of statin therapies. To facilitate the diagnosis of nuanced SIAM clinical cases, the present study proposes an "experience-based" diagnostic algorithm for SIAM. We have analyzed the clinical data of 69 patients diagnosed with SIAM. Sixty-seven patients have been collected from the 55 available and complete case records regarding SIAM in the literature; the other 2 patients represent our direct clinical experience and their case records have been detailed. From the analysis of the clinical features of 69 patients, we have constructed the diagnostic algorithm, which starts from the recognition of suggestive symptoms of SIAM. Further steps provide for CK values dosage, musculoskeletal MR, EMG/ENG of upper-lower limbs and, Anti-HMGCR Ab testing and, where possible, the muscle biopsy. A global evaluation of the collected clinical features may suggest a more severe disease in female patients. Atorvastatin proved to be the most used hypolipidemic therapy.


Field measurement of nickel sediment toxicity: role of acid volatile sulfide.
A field experiment was performed in four freshwater systems to assess the effects of Ni on the benthic macroinvertebrate communities. Sediments were collected from the sites (in Belgium, Germany, and Italy), spiked with Ni, and returned to the respective field sites. The colonization process of the benthic communities was monitored during a nine-month period. Nickel effect on the benthos was also assessed in the context of equilibrium partitioning model based on acid volatile sulfides (AVS) and simultaneously extracted metals (SEM). Benthic communities were not affected at (SEM - AVS) ≤ 0.4 µmol/g, (SEM - AVS)/fraction of organic carbon (f(OC)) < 21 µmol/g organic carbon (OC). Sediments with (SEM - AVS) > 2 µmol/g, (SEM - AVS)/f(OC) > 700 µmol/g OC resulted in clear adverse effects. Uncertainty about the presence and absence of Ni toxicity occurred at (SEM - AVS) and (SEM - AVS)/f(OC) between 0.4 to 2 µmol/g and 21 to 700 µmol/g OC, respectively. The results of our study also indicate that when applying the SEM:AVS concept for predicting metal toxicity in the field study, stressors other than sediment characteristics (e.g., sorption capacity), such as environmental disturbances, should be considered, and the results should be carefully interpreted.


Diversity of Saccharomyces and non-Saccharomyces yeasts in three red grape varieties cultured in the Serranía de Ronda (Spain) vine-growing region.
For the first time, an ecological survey of wine yeasts present in grapes growing in two vineyards located in the region of "Serranía de Ronda" (Málaga, southern Spain) has been carried out. During the 2006 and 2007 vintages, grapes from different varieties were aseptically collected and allowed to ferment spontaneously in the laboratory. From a total of 1586 colonies isolated from microvinifications, 1281 were identified according to ITS polymorphisms and their identity confirmed by sequencing of the D1/D2 region of 26S rDNA. Most of the isolates (84%) corresponded to thirteen different non-Saccharomyces species with Kluyveromyces thermotolerans, Hanseniaspora guilliermondii, Hanseniaspora uvarum and Issatchenkia orientalis accounting for 42.7% of the total. Mitochondrial DNA restriction analysis from the Saccharomyces cerevisiae isolates revealed a low diversity since only eleven different profiles were found, nine of them corresponding to local strains and two to commercial ones that had been used in different campaigns and that very likely were disseminated from the winery to the adjacent vineyard. A different distribution of strains was found in the three grape varieties studied.


The self-help clearinghouse concept: an evaluation of one program and its implications for policy and practice.
Many clearinghouses have been organized within the last decade to promote mutual aid and to provide referral information about self-help groups to potential members. Few of the assumptions that underpin the operation of these programs have been evaluated, however. This paper presents an evaluation of the Self-Help Information Service, a clearinghouse integrated with a generic information and referral service. The results were generally positive with respect to operator and consumer satisfaction, community responsiveness, and the system's capacity to undertake numerous service and research functions. They also pointed up several changes that might be made to improve the system's impact. It is concluded that a new practice specialty might be developed within a clearinghouse context, and that the clearinghouse concept might serve as one cornerstone of a funding policy that supports the self-help approach.


The decline in popularity of the intrauterine device. A survey of general practitioner attitudes and practices in New South Wales.
To assess the attitudes and practices of general practitioners (GPs) in New South Wales in regard to intrauterine device (IUD) use. Randomised group comparison of 100 rural and 100 urban GPs by questionnaire. Sixty-five rural and 66 urban general practitioners took part in the study. Almost 50% of GPs who responded to the questionnaire always discussed the IUD when counselling about contraception, whereas 6% never discussed IUDs. Rural GPs were more likely to discuss IUD use than urban GPs. In the past, 68.7% of GPs had inserted IUDs but only 20.6% still inserted them. Fifty per cent of GPs who did not currently insert IUDs felt they lacked expertise due to less demand for IUDs from women or inadequate training. Prevailing community attitudes towards intrauterine devices have resulted in fewer requests to general practitioners for IUDs, resulting in a lack of expertise in IUD insertion. Increased litigation associated with IUD use, and subsequent publicity, has increased the cost of medical indemnity insurance. All these factors have contributed to fewer GPs being prepared to insert IUDs. Australian women are being deprived of balanced information about the benefits and risks of IUD use and of the possibility of using this very effective, low-cost, low-maintenance method of contraception.


An evaluation of the initial distribution volume of glucose to assess plasma volume during a fluid challenge.
Circulation blood volume can be estimated with the initial distribution volume of glucose (IDVG) method. In a prospective, observational study, we evaluated the effect of a fluid challenge on IDVG in individual patients. In 13 patients after cardiac surgery, IDVG was determined before and after the infusion of 7 mL/kg hydroxyethyl starch over 30 min. Eleven patients not requiring a fluid challenge served as control. IDVG was computed with a one-compartment exponential model, using plasma glucose concentrations at baseline and 3, 4, 5, 6, and 7 min after 5 g of glucose IV bolus. IDVG was repeated 3 times in the control group. IDVG did not change after a fluid challenge (85 +/- 14 versus 93 +/- 14 mL/kg, P = 0.08), and the power of the comparison was 0.25 for a P value of 0.05. The regression coefficient of the exponential fit of glucose versus time was 0.96 +/- 0.03 before, and 0.95 +/- 0.04 after starch infusion (not significant). In the control group, IDVG was 90 +/- 18 mL/kg, and the average individual coefficient of variation was 0.15 +/- 0.08. IDVG seems inadequate to assess individual response to fluid therapy. This limitation may be related to the weak reproducibility of IDVG. The initial distribution volume of glucose (IDVG) is supposed to reflect effective circulating blood volume. We assessed the sensitivity of this method to a fluid challenge in patients receiving a fluid challenge, and the reproducibility in otherwise stable patients. IDVG was not sensitive to a fluid challenge, and reproducibility was poor. Thus, clinical usefulness of IDVG seems limited.


Hetastarch as a prime for cardiopulmonary bypass.
Hetastarch, a synthetic colloid osmotic plasma volume expander, was employed in a prime for cardiopulmonary bypass in 37 patients undergoing myocardial revascularization. Comparison of laboratory values to those of 42 patients undergoing myocardial revascularization using an albumin-containing prime showed lower postoperative platelet counts (p less than 0.02) with hetastarch. There were no differences in chest tube drainage, blood use, plasma hemoglobin, fibrinogen levels, of coagulation times. The hetastarch prime cost $119.50 per patient, whereas the albumin-containing prime cost $321.35 per patient.


Comparison of McGrath, Pentax, and Macintosh laryngoscope in normal and cervical immobilized manikin by novices: a randomized crossover trial.
The aim of this study was to compare tracheal intubation performance regarding the time to intubation, glottic view, difficulty, and dental click, by novices using McGrath videolaryngoscope (VL), Pentax Airway Scope (AWS) and Macintosh laryngoscope in normal and cervical immobilized manikin models. Thirty-five anesthesia nurses without previous intubation experience were recruited. Participants performed endotracheal intubation in a manikin model at two simulated neck positions (normal and fixed neck via cervical immobilization), using three different devices three times each. Performance parameters included intubation time, success rate of intubation, Cormack Lehane laryngoscope grading, dental click, and subjective difficulty score. Intubation time and success rate during first attempt were not significantly different between the 3 groups in normal airway manikin. In the cervical immobilized manikin, the intubation time was shorter (p = 0.012), and the success rate with the first attempt was significantly higher (p < 0.001) when using McGrath VL and Pentax AWS compared with Macintosh laryngoscope. Both VLs showed less difficulty score (p < 0.001) and more Cormack Lehane grade I (p < 0.001) in both scenarios. The incidence of dental clicks was higher with Macintosh laryngoscope compared with McGrath VL in cervical immobilized airway (p < 0.001). McGrath VL and Pentax AWS did not show clinically significant decrease in intubation time, however, they achieved higher first attempt success rate, easier intubation and better glottis view compared with Macintosh laryngoscope by novices in a cervical immobilized manikin model. McGrath VL may reduce the risk of dental injury compared with Macintosh laryngoscope in cervical immobilized scenario. ClinicalTrials.gov (NCT03161730), May 22, 2017 https://clinicaltrials.gov/ct2/hom.


Trace Element Accumulation and Tissue Distribution in the Purpleback Flying Squid Sthenoteuthis oualaniensis from the Central and Southern South China Sea.
Sthenoteuthis oualaniensis is a species of cephalopod that is becoming economically important in the South China Sea. As, Cd, Cr, Cu, Hg, Pb, and Zn concentrations were determined in the mantle, arms, and digestive gland of S. oualaniensis from 31 oceanographic survey stations in the central and southern South China Sea. Intraspecific and interspecific comparisons with previous studies were made. Mean concentrations of trace elements analyzed in arms and mantle were in the following orders: Zn > Cu > Cd > Cr > As > Hg. In digestive gland, the concentrations of Cd and Cu exceed that of Zn. All the Pb concentrations were under the detected limit.


[Employment of a dental hygienist in Germany. 2. The cooperation between dentist and dental hygienist in day to day practice].
The comprehensive range of functions in a dental practice with special emphasis on periodontal cure requires cooperation amongst highly qualified personnel. The dental hygienist has a special standing and is responsible for as well as in charge of important treatment stages, as much as the dentist himself. The treatment stages are of greater relevance to long-lasting therapeutic achievements.


Isolation and characterization of two sub-species of Lp(a), one containing apo E and one free of apo E.
Lipoprotein Lp(a) was isolated by immunoaffinity chromatography using anti apolipoprotein B and anti apolipoprotein (a) immunosorbents. Besides apolipoproteins (a) and B, this fraction was shown to contain apolipoproteins C and E. Therefore, it was decided to further purify this crude Lp(a) into particles containing apolipoprotein E and particles free of apo E, using chromatography with an anti apolipoprotein E immunosorbent. Lp(a), free of apolipoprotein E was cholesterol ester rich and triacylglycerol poor and was found mainly in the LDL size range. In contrast, Lp(a) containing apolipoprotein E was triacylglycerol rich and was distributed mainly in the VLDL and IDL size range. Binding of these two fractions, one containing apo E and one free of it, to the apo B/E receptor of HeLa cells was studied. Both fractions bound to the receptor but the one containing apo E had a better affinity than the one free of apo E. Further studies are needed to identify the clinical importance of these two different entities.


The role of technical, biological, and pharmacological factors in the laboratory evaluation of anticonvulsant drugs. V. Lack of seasonal influences on amygdala kindling in rats.
Previous studies have suggested that seizure models may be affected by seasonal rhythms, even under controlled environmental conditions. In the present experiments in rats with chronically implanted electrodes in the basolateral amygdala, kindling was initiated at different seasons of the year over a period of 3 years. In a total of 109 animals, the following parameters were determined: the threshold for induction of amygdaloid afterdischarges prior to kindling (pre-kindling ADT), the number of daily amygdaloid stimulations to fully kindled (stage 5) seizures, and the post-kindling ADT. No seasonal influences were found with respect to rate of kindling development and post-kindling ADT. In contrast, pre-kindling ADTs appeared to be higher in spring than in other seasons, which, however, could not be reproduced in another spring. Thus, the data do not indicate that seasonal rhythms affect the kindling model of epilepsy.


Facilitating Intimate Partner Violence Education among Pharmacy Students: What Do Future Pharmacists Want to Know?
This paper describes the first step toward creating training tools to improve pharmacy students' and pharmacists' ability to identify intimate partner violence (IPV) among patients and facilitate referrals. The paper's objectives are to evaluate an IPV didactic session adapted for pharmacy students and describe student quantitative and qualitative feedback on the session. Almost 90% of students believed IPV was relevant to their pharmacy careers and that the session improved their ability to recognize IPV. Twenty one percent believed they had encountered a patient they suspected was a victim of IPV. Legal and liability issues, course logistics, skill development, greater specificity and student engagement were themes that emerged. Greater specificity toward pharmacy was recommended to understand the intricacies of legal and professional responsibilities, patient and personal safety risks, and maintaining strong provider/patient relationships. To overcome barriers to screening, assessment and referral, students need opportunities to engage in role-playing and practical application of the knowledge gained.


Cross-regulation between herpesviruses and the TNF superfamily members.
Herpesviruses have evolved numerous strategies to subvert host immune responses so they can coexist with their host species. These viruses 'co-opt' host genes for entry into host cells and then express immunomodulatory genes, including mimics of members of the tumour-necrosis factor (TNF) superfamily, that initiate and alter host-cell signalling pathways. TNF superfamily members have crucial roles in controlling herpesvirus infection by mediating the direct killing of infected cells and by enhancing immune responses. Despite these strong immune responses, herpesviruses persist in a latent form, which suggests a dynamic relationship between the host immune system and the virus that results in a balance between host survival and viral control.


Preoperative binge eating status and gastric bypass surgery: a long-term outcome study.
The primary purpose of the study was to evaluate the effect of preoperative binge status on long-term weight loss outcomes. IRB approval was obtained. This prospective study was initiated in 1997 at a large teaching hospital. Adult patients who participated in the study and attended post-surgery clinic visits for at least 12 months were included. Patients completed the gormally binge eating scale (BES), the beck depression inventory (BDI), and the SF-36 at baseline prior to surgery. All data are expressed as mean +/- SD. Data were analyzed using a Student's t test, pairwise correlation and regression analysis as appropriate. A total of 157 patients (135 women) aged 45 +/- 10 years were recruited. Their preoperative BMI was 50.7 +/- 8.0 kg/m(2). Thirty-seven patients were classified as severe binge eaters (BES >or= 27) prior to surgery. There was no significant difference in their weight loss compared to the rest of the group at any time point up to 6 years after surgery. Patients with significant depressive symptoms (BDI >13) had no significant difference in their weight loss outcomes compared to the rest of the group. Pre-surgery SF-36 scores did not predict differences in weight loss outcome. Pre-surgical binge status, incidence of depressive symptoms and health related quality of life were not predictive of poor weight loss outcomes in patients up to 6 years after gastric bypass surgery, who were able to make lifestyle changes in preparation for surgery and who adhered to scheduled post surgery clinic visits.


Primary non-obstructive megaureter in adults.
Primary non-obstructive megaureter is rarely first diagnosed in adult life. The clinical and radiographic findings in 11 adults presenting with this condition are reviewed. The commonest complaint was pain. In all cases the diagnosis was suggested by intravenous urography, which was usually the initial diagnostic test. Confirmation was aided chiefly by micturating cystography and retrograde pyelography. Cystoscopy was normal. The radiologist can make an early diagnosis in this condition, which requires no treatment, in the absence of complications.


Retrobulbar hemorrhage after sub-Tenon's anesthesia.
We present a case of retrobulbar hemorrhage complicating sub-Tenon's anesthesia in a patient receiving oral anticoagulants. To our knowledge, this has been described only once in the literature.


Replacement of HLA class II serology by the HLA-DR microtitre plate oligotyping assay: a one-year experience in unrelated bone marrow donor selection.
Because the selection of unrelated bone marrow donors requires a more accurate HLA-typing technique than is used for sibling donors, we have replaced class II serology by a rapid and highly discriminative HLA-DR DNA oligotyping assay on microtitre plates. We present here our 1-year experience with class II typing for 112 potential donors identified for 33 consecutive leukaemic patients. Although the donors were selected to be HLA-A, -B, -DR serologically identical, the microtitre plate oligotyping assay detected DR incompatibilities in 52.7% of the patient/donor pairs. One third was due to incorrect or incomplete typing of DR11 to DR16, the others to mismatches for the serologically indistinguishable subtypes of DR1, 11, 13 and 15, known to be relevant for T cell recognition.


Selective inhibition by antiflamrnin-2 of thromboxane B(2) release from isolated and perfused guinea-pig lung.
Antiflammin-2 (AF2) is a nonapeptide corresponding to the amino acid residues 246-254 of lipocortin-1 showing anti-inflammatory activity both in vitro and in vivo. The effect of AF2 on the thromboxane B(2) (TXB(2)) and histamine release from isolated and perfused guinea-pig lungs has been studied. AF-2 (10-100 nM) inhibited leukotriene C(4)- (LTC(4)) (3 ng) and antigen-induced (ovalbumin, 1 mg) TXB(2) release in normal and sensitized lungs, respectively. In contrast AF-2 (100 nM) did not modify TXB(2) release induced by histamine (5 mug) or bradykinin (5 mug) in normal lungs. Antigen-induced histamine release was not affected by 100 nM AF-2 infusion. When tested in chopped lung fragments AF-2 (0.1-25 muM) did not modify the release of histamine and TXB(2) induced by antigen (ovalbumin, 10 mug ml(-1)) or calcium ionophore A 23187 (1 muM). Our results show that the inhibitory effect of AF-2 on TXB(2) release is selective and depends on the stimulus applied. In this respect AF-2 mimics, at least in part, the actions of both glucocorticoids and lipocortin-1.


[Tunisian reptiles. III. Distribution and need for protection of terrestrial and fresh water turtles].
The distribution and habitats in Tunisia of the tortoise Testudo graeca graeca and of the two turtles Emys orbicularis and Mauremys caspica leprosa are investigated throughout the country. The present low level of population density is recent; its causes are precised. The protection, more specially for the two first species, must be very efficient.


In situ and dynamic SERS monitoring of glutathione levels during cellular ferroptosis metabolism.
Ferroptosis is a non-apoptotic cell death regulated by iron-dependent lipid peroxidation. Glutathione (GSH), a key antioxidant against oxidative damage, is involved in one of the most important metabolic pathways of ferroptosis. Herein, an excellent plasmonic nanoprobe was developed for highly sensitive, in situ, dynamic real-time monitoring of intracellular GSH levels during ferroptosis. A nanoprobe was prepared by functionalizing gold nanoparticles (AuNPs) with the probe molecule crystal violet (CV). The fluctuation in the SERS signal intensity of CV via the competitive displacement reaction can be used to detect GSH. The advantages of the plasmonic nanoprobe including low-cost production techniques, outstanding stability and biocompatibility, high specificity and sensitivity towards GSH with a detection limit of 0.05 μM. It enables real-time dynamic monitoring of GSH levels in living cells during erastin-induced ferroptosis. This approach is expected to provide important theoretical support for elucidating the GSH-related ferroptosis metabolic mechanism and advancing our understanding of ferroptosis-based cancer therapy. Overview of the workflow of sensing principle for highly sensitive, in situ and dynamic tracking of intracellular GSH levels during drug-triggered ferroptosis process.


Measurement Scales of Suicidal Ideation and Attitudes: A Systematic Review Article.
The main aim of this study was to accumulate research evidence that introduce validated scales to measure suicidal attitudes and ideation and provide an empirical framework for adopting a relevant assessment tool in studies on suicide and suicidal behaviors. Medical Subject Headings' (MeSH) terms were used to search Ovid Medline, PROQUEST, Wiley online library, Science Direct and PubMed for the published articles in English that reported application of an scale to measure suicidal attitudes and ideation from January 1974 onward. Fourteen suicidal attitude scale and 15 scales for assessing suicidal ideation were identified in this systematic review. No gold standard approach was recognized to study suicide related attitudes and ideations. Special focus on generally agreed dimensions of suicidal ideation and attitudes and cross-cultural validation of the introduced scales to be applicable in different ethnic and socially diverse populations could be a promising area of research for scholars.


Limited predictive value of cardiopulmonary exercise indices in patients with moderate chronic heart failure treated with carvedilol.
Peak oxygen consumption (VO2) is traditionally used for risk stratification in chronic heart failure (CHF); however, its predictive value is unknown with carvedilol treatment. Therefore, we sought to investigate the prognostic role of gas-exchange parameters obtained from symptom-limited cardiopulmonary exercise testing (CPX) in patients with CHF that is treated with carvedilol. A total of 508 consecutive patients (443 men, mean age [+/- SD] 59 +/- 9 years) with a mean left ventricular ejection fraction (LVEF) of 25% +/- 7% underwent CPX. The peak VO2 was 13.9 +/- 3 mL/kg/min; the rate of increase of minute ventilation per unit of increase of carbon dioxide production (VE/VCO2 slope) was 32 +/- 2. Outcomes (cardiovascular death or urgent heart transplantation) were determined when all patients who survived had been observed for a minimum of 6 months. Patients were divided into groups according to treatment (carvedilol and non-carvedilol); 236 patients were treated with carvedilol (46%), at a mean dose of 25 +/-13 mg. The VE/CO2 slope, LVEF, peak VO2, and carvedilol treatment were revealed by means of multivariate analysis to be independent and additional predictors in the total population; VE/VCO2 slope, LVEF, and peak VO2 were revealed to be independent and additional predictors in the patients in the noncarvedilol group (all P <.001); and only peak VO2 was revealed to be an independent and additional predictor in the patients in the carvedilol group (P <.01). In the carvedilol group, mortality rates were 26%, 11%, 10%, and 4% (P <.05) in patients with peak VO2 < or =10 mL/kg/min, >10 to < or =14 mL/kg/min, >14 to 18 mL/kg/min, and > or =18 mL/kg/min, respectively. No difference in mortality rates according to peak VO2 or additional outcome indices were identified in the 212 patients with peak VO2 >10 mL/kg/min. Peak VO2 provides limited predictive information in patients with CHF that is treated with carvedilol, and no additional gas exchange parameter yields supplementary advice.


Location of canal isthmus and accessory canals in the mesiobuccal root of maxillary first permanent molars.
Failure in surgical endodontics may be caused by many factors. Failure is commonly due to improper preparation for the root-end filling and a lack of seal of the resected root end. The aim of this study was to investigate the morphology of resected mesiobuccal (MB) root ends of maxillary first molars and to evaluate the location of the canal isthmus and accessory canals between the MB canals. From 50 selected first permanent molars, sections of the MB root at 3, 4 and 5 mm from the apex were prepared, acid-etched, washed and dried. The apical side of each section was sputter-coated with gold, examined by a scanning electron microscope and photographed. Overall, 18 (36%) of the 50 MB roots had one canal, whereas 32 (64%) had 2 canals. Of the roots with 2 canals, 10 (31.25%) contained either a complete isthmus or accessory canals or both between the 2 main canals. Another 10 (31.25%) showed partial isthmus formation. MB roots exhibit a variety of canal configurations. On the basis of these findings, we propose a classification of the resected root surface of the MB root. Prudent judgement in preparing the canal isthmus, meticulous skill and comprehensive knowledge of root canal anatomy are essential for successful treatment.


Effects of methylphenidate on appetite and growth in children diagnosed with attention deficit and hyperactivity disorder.
The purpose of this study was to determine the levels of leptin, ghrelin, and nesfatin-1 to elucidate the causes of poor appetite and growth retardation in patients receiving methylphenidate therapy for attention deficit hyperactivity disorder. The study was performed on 89 male subjects; 48 patients and 41 healthy controls, aged 7-14 years. Following treatment, patients' leptin levels increased and ghrelin levels decreased while no significant change was found in nesfatin-1 levels. Of the 48 patients, 34 developed lack of appetite. In patients who developed lack of appetite, body weight SDS, body mass index (BMI), and BMI SDS were statistically significantly reduced; moreover, height SDS was reduced, though not to a statistically significant extent. This study attempted to elucidate the mechanisms that mediate the association between methylphenidate and appetite and growth, for which no studies have yet to be published.


Aspects of the ecology of an exposed shore population of dogwhelks Nucella lapillus (L.).
Up to the third year of life Nucella lapillus (L.) could be aged in the laboratory and in the field using shell characters. Monthly counts along transects on an exposed rocky shore have shown that the age groups behave differently, dogwhelks in their first year migrating upshore, and returning to lower levels in the second year. Adults (three years or older) lived and laid egg capsules in the low shore. The most favourable situation for subsequent hatching of these capsules was where they were permanently submerged in sea water.The first requirement of recently hatched young was probably protection from water movement, but they soon gegan feeding on small mussels. The shell height attained by the end of the first winter was related to winter temperatures, but the main growing season was June to November. Adult size was attained in two years, after which the individuals did not usually grow, but those which did grow during the third or succeeding years may have been nonbreeders or have been castrated by the trematode Parorchis acanthus.The age structure of the population suggested that mortality rate decreased with age, and this was confirmed by calculating annual mortality rates for the first three years of life. Heavy mortality in the low shore during the first winter was due mainly to predation by purple sandpipers. In succeeding winters mortality was low, and predation, the main mortality factor, was restricted to the summer months. At this time Cancer pagurus was the most voracious predator, but it was active mainly in the low shore, and the upshore distribution of second year dogwhelks, which were preferred to other age groups, age groups also led to a more economical use of environmental resources, namely food, winter aggregation sites and breeding sites.


CYP2C19 loss-of-function alleles and use of omeprazole or esomeprazole increase the risk of cardiovascular outcomes in patients using clopidogrel.
Our aim was to investigate in a real-life prospective patient cohort how CYP2C19 loss-of-function (LOF) variants and CYP2C19 inhibitor omeprazole or esomeprazole influence the incidence of cardiovascular events in patients using clopidogrel. Data based simultaneously on these factors are conflicting and sparse. A cohort of prospective patients (n = 1972) with acute coronary syndrome (n = 1302) or symptomatic chronic coronary disease (n = 656) was followed for 365 days after hospitalization with information on purchased prescription drugs, hospital discharge, death, and genotype for CYP2C19*2, CYP2C19*3, and CYP2C19*8 LOF variants. The primary study outcome measurement was cardiovascular death or recurring myocardial infarction or stroke. Altogether, 608 patients (30.8%) carried CYP2C19 LOF alleles. During the 365-day follow-up 252 patients (12.8%) had an ischemic vascular event. Cardiovascular events were significantly more frequent in carriers of CYP2C19 LOF alleles (14.8%, 95% confidence interval [CI], 11.7-17.8) than in non-carriers (10.8%, 95% CI, 9.0-12.6, p = 0.0159). Omeprazole or esomeprazole use was similar among LOF allele carriers (n = 131, 21.5%) and non-carriers (n = 250, 18.3%, p = 0.185). Cardiovascular events were significantly more common in a composite group consisting of all CYP2C19 LOF carriers regardless of proton pump inhibitor use status and non-carriers using omeprazole or esomeprazole than in non-carriers not using omeprazole or esomeprazole (14.8%, 95% CI, 12.2-17.3 vs. 9.9%, 95% CI, 8.0-11.9, p = 0.00173). We observed significantly more cardiovascular events in carriers of CYP2C19 LOF variants and in non-carriers using omeprazole or esomeprazole. For optimal patient care, both genetics and concomitant medication should be considered.


An angiotensin II receptor antagonist attenuates left ventricular dilatation after myocardial infarction in the hypertensive rat.
The aims were (1) to investigate the effect of hypertention on left ventricular dilatation and haemodynamic alterations following acute myocardial infarction in spontaneously hypertensive rats (SHR) and normotensive rats (WKY); (2) to compare haemodynamic indices between the two groups; (3) to assess whether the angiotensin II type 1 receptor antagonist (AIIA), TCV-116, prevented left ventricular dilatation after myocardial infarction; and (4) to compare the effect of AIIA with that of the angiotensin converting enzyme (ACE) inhibitor, delapril. Myocardial infarction was produced in SHR and WKY by coronary artery ligation. Haemodynamic measurements were obtained three weeks later in rats that had been treated from the next day after the operation for three weeks with TCV-116 (1 mg.kg-1.d-1) or delapril (1 g.litre-1 in drinking water), and in untreated controls. After myocardial infarction, left ventricular weight, and left ventricular weight were greater in SHR than in normotensive rats. Right ventricular weight, left ventricular end diastolic pressure, and LVEDVI correlated positively with infarct size in both SHR and WKY and these slopes were steeper in SHR than in WKY (P < 0.05). TCV-116 and delapril each significantly attenuated the increases in left ventricular end diastolic pressure, left ventricular weight, right ventricular weight, and LVEDVI following myocardial infarction in both in WKY and SHR, and shifted pressure-volume curve significantly to the left. Hypertension accelerates left ventricular dilatation and haemodynamic alterations following myocardial infarction in rats. These effects are attenuated by an angiotensin II type 1 receptor antagonist as well as by an ACE inhibitor.


Hilar hepatojejunostomy in resection of carcinoma of the main hepatic duct junction.
Two patients with carcinoma of the main hepatic duct junction had resection followed by reconstruction between a Roux-en-Y loop of jejunum and the hepatic tissue surrounding the bile ducts at the hilum of the liver. At 18 and 11 month intervals postoperatively, they are both free from known tumor recurrence and have normal serum bilirubin levels.


A multicentre review of the histology of 1012 periocular basal cell carcinomas.
To evaluate primary periocular basal cell carcinomas (BCCs) in depth including comparing histological margins with subtype, location and surgical specialty after wide local excision. A retrospective review was performed for all BCCs excised from three hospitals over 5 years, covering a population of just over 1 million. Tumours were classified according to histological subtype location. Incomplete excision rates and margins were analysed in detail and comparisons made. The most common subtype found was nodular followed by infiltrative. Lesions were most commonly located at the lower lid. Infiltrative BCCs were associated with perineural invasion and incomplete excision despite the largest peripheral margins. Superficial BCCs had the smallest mean peripheral margin but the largest mean deep margin. 2 mm histological margins gave an 83.7% complete excision rate, 6.4% incomplete excision rate and 7.1% where the clearance margin was 0.3 mm or less. Distribution of eyelid BCCs based on subtype and periocular location mirrored the general consensus. Infiltrative BCCs should be excised with wider margins or referred for Mohs surgery, especially if the medial canthus is involved. Superficial BCCs should be excised with wider but shallower surgical margins. Ophthalmologists were more likely than dermatologists or plastic surgeons to incompletely excise a periocular BCC, which is reflective of their more difficult case mix.


Paris Prospective Study III: a study of novel heart rate parameters, baroreflex sensitivity and risk of sudden death.
Resting heart rate has been related to the risk of cardiovascular disease and sudden death in several large prospective studies. To investigate prospectively the association of novel heart rate parameters and of carotid artery stiffness with sudden death and other cardiovascular disease. The Paris Prospective Study III (PPS3) is a new, ongoing French prospective study. From June 2008 to December 2011, 10,000 men and women aged 50-75 years who will have a preventive medical check-up at the Centre d'Investigations Préventives et Cliniques in Paris (France), will be enrolled in the study, after signing an informed consent. In addition to the general health examination, each subject's heart rhythm will be recorded during the course of the health check-up (approximately 2(1/2) h) and an echo-tracking of the right carotid bulb will be performed by trained technicians. A bio bank and DNA bank will be established for further biomarker and genetic analyses. The occurrence of cardiovascular disease including acute coronary syndrome, stroke, peripheral artery disease and sudden death, and of mortality, of the participants will be followed up during 20 years. With an estimated mean annual rate of sudden death of 0.1% and its increasing incidence rate with age, between 250 and 300 sudden deaths are expected. This unique study should provide new insights into the regulation of heart rate and blood pressure and should enable to identify novel heart rate parameters that are associated with sudden death.


Liver metal levels and expression of genes related to iron homeostasis in rhesus monkeys after inhalational manganese exposure.
Here we present data on liver metal levels and expression of genes related to iron homeostasis in rhesus monkeys after inhalational manganese exposure. Archived liver samples from rhesus monkeys exposed to 0 (n=6), 0.06 (n=6), 0.3 (n=4) and 1.5 (n=4) mg/m(3) manganese inhalation for 65 days were obtained from a published study ("Tissue manganese concentrations in young male rhesus monkeys following subchronic manganese sulfate inhalation" [1]). Samples were analyzed by spectroscopy, immunoblotting and quantitative PCR to assess metal levels and gene expression. Liver manganese and iron levels were linearly correlated although only the intermediate manganese exposure level (0.3 mg Mn/m(3)) led to a statistically significant increase in liver iron levels.


Increased peripheral resistance in heart failure: new evidence suggests an alteration in vascular smooth muscle function.
Increased peripheral resistance is a hallmark of chronic heart failure and has been primarily attributed to neurohumoral pathways involving both the renin-angiotensin and sympathetic nervous systems. The increased resistance is thought to serve as a compensatory mechanism to help maintain perfusion to the vital organs by sustaining blood pressure in the fate of a failing heart. Local mechanisms, and in particular endothelial dysfunction, have also been shown to be important contributors in regulating arterial resistance and vascular remodeling in this disease. In this issue of the British Journal of Pharmacology, Gschwend et al. (2003) present new data suggesting that in the absence of a functional endothelium, myogenic constriction of small pressurized mesenteric arteries, an intrinsic property of vascular smooth muscle cells, is enhanced in a coronary artery ligation-induced myocardial infarction model of congestive heart failure (CHF) in the rat. The increased myogenic tone appears to be tightly linked to angiotensin II type 1 receptors (AT(1)). The possibility that CHF-induced stimulation of myogenic constriction is due to the local release of preformed angiotensin II or constitutive upregulation of the AT(1) receptor signaling pathways are discussed along with other potential cellular and molecular mechanisms previously suggested to play a role in myogenic reactivity.


Effects of Cytochrome P450 3A4 Induction and Inhibition on the Pharmacokinetics of BI 425809, a Novel Glycine Transporter 1 Inhibitor.
Increased glycine availability at the synaptic cleft may enhance N-methyl-D-aspartate receptor signalling and provide a promising therapeutic strategy for cognitive impairment associated with schizophrenia. These studies aimed to assess the pharmacokinetics of BI 425809, a potent glycine-transporter-1 inhibitor, when co-administered with a strong cytochrome P450 3A4 (CYP3A4) inhibitor (itraconazole) and inducer (rifampicin). In vitro studies using recombinant CYPs, human liver microsomes, and human hepatocytes were conducted to determine the CYP isoforms responsible for BI 425809 metabolism. In addition, two open-label, fixed-treatment period, phase I studies in healthy male volunteers are described. Period 1: participants received oral BI 425809 25 mg (single dose) on day 1; period 2: participants received multiple doses, across 10 days, of oral itraconazole or rifampicin combined with a single dose of oral BI 425809 25 mg on day 4/7 of the itraconazole/rifampicin treatment, respectively. Pharmacokinetic and safety endpoints were assessed in the absence/presence of itraconazole/rifampicin and included area under the concentration-time curve (AUC) over the time interval 0-167 h (AUC0‒167; itraconazole), 0-168 h (AUC0‒168; rifampicin), or 0-infinity (AUC0-∞; rifampicin and itraconazole), maximum measured concentration (Cmax) of BI 425809, and adverse events. In vitro results suggested that CYP3A4 accounted for ≥ 90% of the metabolism of BI 425809. BI 425809 exposure (adjusted geometric mean ratio [%]) was higher in the presence of itraconazole (AUC0‒167: 265.3; AUC0-∞: 597.0; Cmax: 116.1) and lower in the presence of rifampicin (AUC0‒168: 10.3; AUC0-∞: 9.8; Cmax: 37.4) compared with BI 425809 alone. Investigational treatments were well tolerated. Systemic exposure of BI 425809 was altered in the presence of strong CYP3A4 modulators, corroborating in vitro results that CYP3A4 mediates a major metabolic pathway for BI 425809. NCT02342717 (registered on 15 January 2015) and NCT03082183 (registered on 10 March 2017).


Musculoskeletal and central pain at 1 year post-stroke: associated factors and impact on quality of life.
Pain is common in post-stroke patients and has been shown to be associated with depression, fatigue, and decreased quality of life (QOL). However, studies examining different types of post-stroke pain are scarce. We investigated differences in the related factors and their QOL impacts between musculoskeletal pain (MSP) and central post-stroke pain (CPSP). We assessed 364 consecutive stroke patients who were admitted to Asan Medical Center and contacted 12 months after stroke onset. We categorized pain and paresthesia as MSP, CPSP, combined pain, or other pain. Post-stroke depression (Beck Depression Inventory), fatigue (Fatigue Severity Scale), sleep disturbance (Verran Snyder-Halpern scale), social support (ENRICHED Social Support Instrument), and QOL (Medical Outcome Study 36-Item Short Form) were assessed. Of the 364 patients analyzed, 135 (37.1%) had pain, 78 (21.4%) had MSP, 22 (6.0%) had CPSP, 16 (4.4%) had combined pain, and 19 (5.2%) had other pain. In multivariate analyses, CPSP was related to modified Rankin scale (P=.004), sensory dysfunction (P<.001), thalamus lesion (P=.001), medulla lesion (P=.007), and fatigue (P=.026). MSP was related to motor dysfunction (P<.001) and fatigue (P=.003). QOL varied among groups with different types of pain (P<.001) and was the poorest in patients with combined pain. Pain is common 12 months post-stroke. The factors associated with CPSP and MSP differ, but are both closely associated with fatigue rather than depression. QOL is the poorest in patients with combined pain. Management of pain and fatigue may be important for improving the QOL in stroke patients.


Conserved role for PCBP1 in altered RNA splicing in the hippocampus after chronic alcohol exposure.
We previously discovered using transcriptomics that rats undergoing withdrawal after chronic ethanol exposure had increased expression of several genes encoding RNA splicing factors in the hippocampus. Here, we examined RNA splicing in the rat hippocampus during withdrawal from chronic ethanol exposure and in postmortem hippocampus of human subjects diagnosed with alcohol use disorder (AUD). We found that expression of the gene encoding the splicing factor, poly r(C) binding protein 1 (PCBP1), was elevated in the hippocampus of rats during withdrawal after chronic ethanol exposure and AUD subjects. We next analyzed the rat RNA-Seq data for differentially expressed (DE) exon junctions. One gene, Hapln2, had increased usage of a novel 3' splice site in exon 4 during withdrawal. This splice site was conserved in human HAPLN2 and was used more frequently in the hippocampus of AUD compared to control subjects. To establish a functional role for PCBP1 in HAPLN2 splicing, we performed RNA immunoprecipitation (RIP) with a PCBP1 antibody in rat and human hippocampus, which showed enriched PCBP1 association near the HAPLN2 exon 4 3' splice site in the hippocampus of rats during ethanol withdrawal and AUD subjects. Our results indicate a conserved role for the splicing factor PCBP1 in aberrant splicing of HAPLN2 after chronic ethanol exposure. As the HAPLN2 gene encodes an extracellular matrix protein involved in nerve conduction velocity, use of this alternative splice site is predicted to result in loss of protein function that could negatively impact hippocampal function in AUD.


Direct and indirect effects of marijuana use on the risk of fatal 2-vehicle crash initiation.
Marijuana and alcohol each play a significant role in fatal crash initiation. We decomposed the total effect of marijuana use in the presence or absence of alcohol on fatal crash initiation into direct and indirect effects. Pair-matched data on 5856 culpable drivers (initiators) and 5856 nonculpable drivers (noninitiators) involved in the same fatal 2-vehicle crashes recorded in the Fatality Analysis Reporting System between 2011 and 2016 were analyzed using the conditional logistic regression model and the unified mediation and interaction analysis framework. Crash initiators were more likely than noninitiators to test positive for marijuana (16.1% vs. 9.2%, P < 0.001), alcohol (28.6% vs. 9.7%, P < 0.001) and both substances (6.3% vs. 1.6%, P < .0001). Adjusted odds ratios of fatal 2-vehicle crash initiation revealed a positive interaction on the additive scale between marijuana and alcohol. Of the total effect of marijuana use on fatal 2-vehicle crash initiation, 68.8% was attributable to the direct effect (51.5% to controlled direct effect and 17.3% to reference interaction effect with alcohol) and 31.2% to the indirect effect (7.8% to mediated interaction effect and 23.4% to pure indirect effect through alcohol). Our results indicate that the increased odds of fatal 2-vehicle crash initiation associated with marijuana use is due mainly to the direct effect.


Direct Evidence for Microdomain-Specific Localization and Remodeling of Functional L-Type Calcium Channels in Rat and Human Atrial Myocytes.
Distinct subpopulations of L-type calcium channels (LTCCs) with different functional properties exist in cardiomyocytes. Disruption of cellular structure may affect LTCC in a microdomain-specific manner and contribute to the pathophysiology of cardiac diseases, especially in cells lacking organized transverse tubules (T-tubules) such as atrial myocytes (AMs). Isolated rat and human AMs were characterized by scanning ion conductance, confocal, and electron microscopy. Half of AMs possessed T-tubules and structured topography, proportional to cell width. A bigger proportion of myocytes in the left atrium had organized T-tubules and topography than in the right atrium. Super-resolution scanning patch clamp showed that LTCCs distribute equally in T-tubules and crest areas of the sarcolemma, whereas, in ventricular myocytes, LTCCs primarily cluster in T-tubules. Rat, but not human, T-tubule LTCCs had open probability similar to crest LTCCs, but exhibited ≈ 40% greater current. Optical mapping of Ca(2+) transients revealed that rat AMs presented ≈ 3-fold as many spontaneous Ca(2+) release events as ventricular myocytes. Occurrence of crest LTCCs and spontaneous Ca(2+) transients were eliminated by either a caveolae-targeted LTCC antagonist or disrupting caveolae with methyl-β-cyclodextrin, with an associated ≈ 30% whole-cell ICa,L reduction. Heart failure (16 weeks post-myocardial infarction) in rats resulted in a T-tubule degradation (by ≈ 40%) and significant elevation of spontaneous Ca(2+) release events. Although heart failure did not affect LTCC occurrence, it led to ≈ 25% decrease in T-tubule LTCC amplitude. We provide the first direct evidence for the existence of 2 distinct subpopulations of functional LTCCs in rat and human AMs, with their biophysical properties modulated in heart failure in a microdomain-specific manner.


Subxiphoid video-assisted thoracoscopic surgery versus standard video-assisted thoracoscopic surgery for anatomic pulmonary lobectomy.
A subxiphoid surgical approach to thoracic cavity operations has potential advantages such as preventing injuries to intercostal nerves and vessels due to the bypass of the intercostal space during thoracic surgery. The aim of this study was to compare the feasibility and efficacy of the subxiphoid and standard transthoracic approaches for anatomic pulmonary lobectomy in a canine model. Nineteen dogs were assigned for pulmonary lobectomy using either the subxiphoid (n = 10) or standard transthoracic approaches (n = 9). Each group underwent thoracic exploration and anatomic pulmonary lobectomy. Subxiphoid thoracoscopy was performed with a flexible bronchoscope via a 3-cm incision over the xiphoid process. In the conventional thoracoscopy group, approach to the thoracic cavity was obtained through a 3-cm incision over the seventh intercostal space. Physiological parameters (respiratory rate and body temperature) and blood samples (white blood cell counts and arterial blood gases) were collected during the preoperative and postoperative periods. Surgical outcomes data (operating time, operative complications, and body weight gain) were also collected and compared between the groups. The animals were sacrificed 14 d after surgery for necropsy evaluations. Anatomic pulmonary lobectomy was successfully performed without intraoperative and postoperative complications in all animals. There were no significant differences in the mean operating times or weight gain after surgery between the subxiphoid and the standard transthoracic approach groups. In terms of physiological and pulmonary parameters, there were no observed differences between the two surgical groups for respiratory rate, body temperature, white blood cell counts, and arterial blood gases at any time during the study. Necropsy confirmed the success of lobectomy without complication in all studied animals. This study demonstrated that the subxiphoid approach was comparable with the standard transthoracic approach for anatomic pulmonary lobectomy, in terms of feasibility and effectiveness.


Disclosure and help-seeking behaviors related to sexual and physical violence in childhood and adolescence: Results from the Namibia Violence Against Children and Youth Survey.
Violence disclosure and help-seeking can mitigate adverse health effects associated with childhood violence, but little is known about facilitators and barriers of disclosure and help-seeking behaviors in sub-Saharan Africa. To understand factors associated with disclosure and help-seeking to inform care. Participants aged 13-24 years old in the 2019 Namibia Violence Against Children and Youth Survey (VACS). We assessed the prevalence of victimization, disclosure, and help-seeking and examined factors associated with violence disclosure and help-seeking, separately, by gender. 4211 girls and 980 boys participated in the Namibia VACS. The prevalence of childhood sexual violence differed significantly by gender (15.7% among girls, 9.8% among boys), but physical violence prevalence did not differ by gender. Among victims of sexual violence, 57.3% of girls disclosed and 10.4% sought help, compared with only 30.7% and 3.2% of boys. Among victims of physical violence, 61.1% of girls and 53.4% of boys disclosed, and 16.9% of girls and 17.7% of boys sought help. Older age, social support, and experiencing more types of violence were associated with sexual violence disclosure among boys, but none of these factors were associated with sexual violence disclosure among girls. Lower education, perpetrator type, and witnessing violence were associated with physical violence disclosure among girls, while peer support and perpetrator type were associated with physical violence disclosure among boys. Factors associated with childhood violence differed by gender and violence type in Namibia, highlighting a need for gender-specific violence services to facilitate violence disclosure and help-seeking.


Squamous metaplasia of the verumontanum with obstruction due to hypertrophy: long-term effects of estrogen on the prostate in an aging male-to-female transsexual.
We report on a 30-year-old male-to-female transsexual who had been treated with diethylstilbestrol and Premarin from 1954 to the present. A sex change operation was done. In May 1979 transurethral resection was performed for obstruction due to the enlargement of the verumontanum. Transurethral resection was repeated in January 1983 for obstructive symptoms. The interesting effect of the estrogens on the verumontanum and prostate is described and illustrated. The squamous metaplasia is compared to that seen in the prostate of a true hermaphrodite.


Sparse observations induce large biases in estimates of the global ocean CO2 sink: an ocean model subsampling experiment.
Estimates of ocean [Formula: see text] uptake from global ocean biogeochemistry models and [Formula: see text]-based data products differ substantially, especially in high latitudes and in the trend of the [Formula: see text] uptake since 2000. Here, we assess the effect of data sparsity on two [Formula: see text]-based estimates by subsampling output from a global ocean biogeochemistry model. The estimates of the ocean [Formula: see text] uptake are improved from a sampling scheme that mimics present-day sampling to an ideal sampling scheme with 1000 evenly distributed sites. In particular, insufficient sampling has given rise to strong biases in the trend of the ocean carbon sink in the [Formula: see text] products. The overestimation of the [Formula: see text] flux trend by 20-35% globally and 50-130% in the Southern Ocean with the present-day sampling is reduced to less than [Formula: see text] with the ideal sampling scheme. A substantial overestimation of the decadal variability of the Southern Ocean carbon sink occurs in one product and appears related to a skewed data distribution in [Formula: see text] space. With the ideal sampling, the bias in the mean [Formula: see text] flux is reduced from 9-12% to 2-9% globally and from 14-26% to 5-17% in the Southern Ocean. On top of that, discrepancies of about [Formula: see text] (15%) persist due to uncertainties in the gas-exchange calculation. This article is part of a discussion meeting issue 'Heat and carbon uptake in the Southern Ocean: the state of the art and future priorities'.


Establishment of a T-Ag and NF-kappaB binding elements gene co-transfected stable HUVECs cell line.
To set up a T-Ag gene transfected stable human umbilical venous endothelial cells (HUVECs) cell line and a T-Ag, nuclear transcriptional factor kappa B (NF-kappaB) binding elements linked with luciferase reporter gene co-transfected stable HUVECs cell line. Cultured HUVECs were transfected with pCI-neo-T-Ag and pRSV-luc-3XkappaB by lipofectin. The G418 selected monoclones were subcultured. The expression of marker protein, vWF and the characteristic of uptake of lipids were compared by Western blotting and immunocytochemistry in non-transfected and transfected HUVECs. The reporter gene assay was done in the presence of TNF-alpha. A T-Ag gene transfected stable HUVECs cell line and a T-Ag and NF-kappaB binding elements linked with luciferase reporter gene co-transfected stable HUVECs cell lines were set up. The expression of vWF of these cell lines was similar with those in non-transformed HUVECs. The function of uptaking of lipids was preserved as well in transfected cell lines. Furthermore, TNF-alpha, a typical cytokine increasing the activity of NF-kappaB was used to treat the transfected cells O/N. The higher luciferase reporter gene activity was seen. A pCI-neo-T-Ag and pRSV-luc-3X kappaB co-transfected stable HUVECs cell line might be used to check reporter gene activity directly. It might be a useful tool to screen drugs acting on transcription level.


Risk of atrial fibrillation and stroke among older men exposed to prolonged endurance sport practice: a 10-year follow-up. The Birkebeiner Ageing Study and the Tromsø Study.
Endurance sport practice is associated with a high prevalence of atrial fibrillation (AF), which increases the risk of stroke in the general population. However, stroke risk in endurance athletes with AF is sparsely investigated. Most studies have been limited by design and are largely restricted to younger and middle-aged populations. Thus, we aimed to investigate AF and stroke risk in older athletes exposed to prolonged endurance training. During a 10-year period, 505 male athletes aged ≥65 years frequently participating in a long-distance ski race were compared with 1867 men of the same age from the general population. The main exposure was endurance sport practice with self-reported AF and stroke as outcomes. Stroke risk was further examined by joint modelling of AF and endurance practice. Statistical analysis was conducted with a modified Poisson model. Athletes (median age: 68, range: 65-90) participated in a long-distance ski race over a median of 14 years (range: 1-53). Prevalence (28.5% vs 17.8%) and adjusted risk of AF (risk ratio (RR): 1.88, 95% CI: 1.49 to 2.37) were higher in athletes compared with non-athletes, whereas the prevalence (5.4% vs 9.7%) and risk of stroke were lower (RR: 0.60, 95% CI: 0.37 to 0.95). Compared with athletes without AF, risk of stroke was twofold in athletes (RR: 2.38, 95% CI: 1.08 to 5.24) and nearly fourfold in non-athletes (RR: 3.87, 95% CI: 1.98 to 7.57) with AF. Although older male endurance athletes experienced an increased risk of AF, the long-term risk of stroke was substantially reduced compared with non-athletes.


Diabetes mellitus in the elderly: diagnostic features.
The new diagnostic criteria of the diabetes do not consider the age of the subjects. It has been demonstrated that the fasting glucose values as well as the glycemia levels after oral glucose load increase with age. Therefore, it is necessary to evaluate whether the new diagnostic criteria are valid for the elderly subjects also. In spite of the findings that among the subjects with fasting glycemia of 126-140 mg/ml subsequent controls after long times often revealed the presence of impaired fasting glucose (IFG) and numerous cases with IFG displayed values <110 mg/dl after longer times, the present authors accept the new diagnostic criteria even for the elderly subjects. However, they emphasize the importance of distinguishing diabetes in the elderly in subclasses, such as clinically manifest diabetes, mild diabetes and diabetic glucose tolerance (DGT) type, in order to establish the early diagnosis of diabetes, and therefore, to prevent the chronic vascular complications.


Colesevelam hydrochloride does not cause maternal or fetal toxicity in rats and rabbits.
WelChol (colesevelam hydrochloride), a bile acid sequestrant for the treatment of hypercholesterolemia, was evaluated for adverse effects on reproduction and fetal development using standard preclinical tests. During gestation, Sprague-Dawley rats used in the developmental toxicity study received feed, feed/control article or feed plus 300, 1,000 or 3,000 mg/kg/day colesevelam whereas rats in the pre- and postnatal toxicity study received vehicle or 100, 300 or 1,000 mg/kg/day colesevelam via gavage. New Zealand white rabbits received control or 100, 500 or 1,000 mg/kg/day colesevelam via gavage. No deaths, premature deliveries or gross pathologic lesions were observed up to gestation day (GD) 20 for rats and GD 28 for rabbits. No significant differences in the number of pregnant animals, average litter size, percentage of viable fetuses, fetal body weights, number of corpora lutea, fetal viability, or gross malformations were observed versus controls. Pre- and postnatal effects were assessed in pregnant rats receiving 100, 300 or 1,000 mg/kg/day colesevelam from GD 6 to postpartum day 22. Gestation, parturition and lactation in F(0) generation dams were similar between treatment and control groups. Colesevelam did not affect physical or neurological development or induce gross pathological changes in F(1) generation rats. Colesevelam does not produce developmental toxicity in rats or rabbits, nor does it exhibit pre- or postnatal toxicity in rats at the tested doses.


[Methods of measuring the mechanical stresses on the human lumbar spine and their results].
The authors in a review of the literature and their personal studies, report the various measurements methods of the stresses exerted on the lumbar spine, with their results. This study comprises three chapters: study of an isolated spinal segment, static study of the lumbar spine and dynamic study of the lumbar spine.


Association study between CD30 and CD30 ligand genes and type 1 diabetes in the Japanese population.
CD30-CD30 ligand (CD30L) signal transduction appears to protect against autoimmune diabetes by preventing expansion of autoreactive T cells and suppressing Th1-cytokine response. The purpose of this study was to determine whether CD30 or CD30L genes serve as a novel susceptibility gene for type 1 diabetes in humans. We screened CD30 and CD30L genes for polymorphisms in Japanese patients with type 1 diabetes and control subjects. Then, association studies were performed between each of the identified polymorphisms and type 1 diabetes. Direct-sequencing analysis of the CD30 and CD30L genes revealed four polymorphisms: one in the CD30 gene (-201G/A from the transcription start site), and three in the CD30L gene [CA repeat in the promoter, 276G/A in the exon 3, -73T/C in the intron 3 (IVS3 -73T/C)]. Association studies revealed no association between the CD30 and CD30L genes and type 1 diabetes in the whole population. In the female and male subpopulations, however, the frequency of (CA)(9) allele of the CD30L gene promoter or T allele of IVS3 -73T/C polymorphism in the CD30L gene was slightly higher in female patients with type 1 diabetes than that in control females. In conclusion, we could not find significant association between CD30 or CD30L genes and type 1 diabetes, but (CA)(9) allele in the promotor or T allele of -73T/C in intron 3 in CD30L gene might play a minor role in the pathogenesis of type 1 diabetes, only in the Japanese female population.


Vegetation distribution along mountain environmental gradient predicts shifts in plant community response to climate change in alpine meadow on the Tibetan Plateau.
Plants are particularly sensitive to climate change in alpine ecosystem of the Tibetan Plateau. The various mountain micro-climates provide a natural gradient for space-for-time substitution research that plant responses to climate change. In this study, we surveyed the plant community in term of species composition, diversity and biomass across 189 sites on a hill of the Tibetan Plateau and analysed the individual and integrated effects of soil temperature and moisture on the plant community. The results showed that, at the quadrat scale, there were decrease in richness of 1.08 species for every 1 °C increase in soil temperature and 3.56 species for every 10% decrease in soil moisture. The integrated effects of increasing soil temperature and decreasing moisture are expected to lead to a rapid decrease in species richness. Biomass had no significant correlation with soil temperature but significantly decreased with soil moisture decreasing (p < 0.01). Biomass would decrease when soil moisture was below 20%, no matter how the change of soil temperature. We also found that gramineae and perennial forbs were sensitive to climate change. With soil temperature increased, the proportion of gramineae increased, whereas the proportion of perennial forbs decreased. The integrated effects of soil temperature increasing and moisture decreasing caused a shift from sedge-controlled to gramineae-controlled communities in alpine meadow. This study not only enhances our understanding of mountain plant community dynamics under climate change, but also predicts the shift of vegetation response to climate change on high-elevation alpine meadow.


The electrosurgical operation of vulvar carcinoma with postoperative irradiation of inguinal lymph nodes.
The results of treatment in the department of 607 patients with invasive squamous cell carcinoma of the vulva between 1952 and 1980 is described and analyzed. The absolute 5-year cure rate in these patients was 60.3%. Particular attention was given to lymph node status (TNM system) in the analysis of the last 141 patients treated. The absolute 5-year survival rate was 67% for the N0-N1 patients and 43% for the N2-N3 patients. Patients were treated uniformly by means of electrosurgical operation and postactinic irradiation of the inguinal lymph nodes. Operative lymphadenectomy was performed only in 5% of cases when the diameter of inguinal lymph nodes was greater than 2 cm. This simple surgical technique, in combination with irradiation of inguinal lymph nodes, gives excellent results and avoids the complications associated with inguinofemoral lymphadenectomy. Owing to its combination of electrosurgical operation of the vulva and irradiation of the inguinal regions as a standard procedure, the treatment involves extremely low strain on the patient and is almost free of complications. This seems to be particularly important as the results of our treatment are not less satisfactory than those of more aggressive procedures.


Enhancement of Soybean Meal Alters Gut Microbiome and Influences Behavior of Farmed Atlantic Salmon (Salmo salar).
Atlantic salmon (Salmo salar) is one of the worlds most domesticated fish. As production volumes increase, access to high quality and sustainable protein sources for formulated feeds of this carnivorous fish is required. Soybean meal (SBM) and soy-derived proteins are the dominant protein sources in commercial aquafeeds due to their low-cost, availability and favorable amino acid profile. However, for Atlantic salmon, the inclusion of soybean meal (SBM), and soy protein concentrate (SPC) in certain combinations can impact gut health, which has consequences for immunity and welfare, limiting the use of soy products in salmonid feeds. This study sought to address this challenge by evaluating two gut health-targeted enhancements of SBM for inclusion in freshwater phase salmon diets: enzyme pre-treatment (ETS), and addition of fructose oligosaccharide (USP). These were compared with untreated soybean meal (US) and fish meal (FM). This study took a multi-disciplinary approach, investigating the effect on growth performance, gut microbiome, and behaviors relevant to welfare in aquaculture. This study suggests that both enhancements of SBM provide benefits for growth performance compared with conventional SBM. Both SBM treatments altered fish gut microbiomes and in the case of ETS, increased the presence of the lactic acid bacteria Enterococcus. For the first time, the effects of marine protein sources and plant protein sources on the coping style of salmon were demonstrated. Fish fed SBM showed a tendency for more reactive behavior compared with those fed the FM-based control. All fish had a similar low response to elicited stress, although ETS-fed fish responded more actively than US-fed fish for a single swimming measure. Furthermore, SBM-fed fish displayed lower repeatability of behavior, which may indicate diminished welfare for intensively farmed fish. The implications of these findings for commercial salmonid aquaculture are discussed.


A novel multiplex tetra-primer ARMS-PCR for the simultaneous genotyping of six single nucleotide polymorphisms associated with female cancers.
The tetra-primer amplification refractory mutation system PCR (T-ARMS-PCR) is a fast and economical means of assaying SNP's, requiring only PCR amplification and subsequent electrophoresis for the determination of genotypes. To improve the throughput and efficiency of T-ARMS-PCR, we combined T-ARMS-PCR with a chimeric primer-based temperature switch PCR (TSP) strategy, and used capillary electrophoresis (CE) for amplicon separation and identification. We assessed this process in the simultaneous genotyping of four breast cancer-and two cervical cancer risk-related SNPs. A total of 24 T-ARMS-PCR primers, each 5'-tagged with a universal sequence and a pair of universal primers, were pooled together to amplify the 12 target alleles of 6 SNPs in 186 control female blood samples. Direct sequencing of all samples was also performed to assess the accuracy of this method. Of the 186 samples, as many as 11 amplicons can be produced in one single PCR and separated by CE. Genotyping results of the multiplex T-ARMS-PCR were in complete agreement with direct sequencing of all samples. This novel multiplex T-ARMS-PCR method is the first reported method allowing one to genotype six SNPs in a single reaction with no post-PCR treatment other than electrophoresis. This method is reliable, fast, and easy to perform.


Improvement of salicylic acid biological effect through its encapsulation with silica or chitosan.
Attacks of necrotrophic and biotrophic fungi affect a large number of crops worldwide and are difficult to control with fungicides due to their genetic plasticity. Encapsulation technology is a good alternative for controlling fungal diseases. In this work, encapsulated samples of salicylic acid (SA) with silica (Si:SA) or chitosan (Ch:SA) at three different ratios were prepared by spray drying, and morphological and physicochemical characterised. Therefore, size distribution, specific surface area, thermal stability, encapsulation efficiency, and in-vitro SA release were determined. Biological activity of encapsulated samples were tested against different fungi of agricultural interest at various concentrations (0-1000 µM). Treatments prepared with the lowest ratios for both capsules, were found to have the best antifungal effect in an in vitro system, inhibiting the mycelial growth of Alternaria alternata, Botrytis cinerea, Fusarium oxysporum and Geotrichum candidum. Similarly, treatments with the lowest ratios of both encapsulated samples reduced free SA toxicity on Arabidopsis thaliana seeds. In this system, plants treated with capsules had higher root and rosette development than those treated with free SA. In conclusion, a product with a great potential in agriculture that shows high antifungal capacity and low toxicity for plants have been developed through a controlled and industrially viable process.


Cell type-specific expression of bovine keratin genes as demonstrated by the use of complementary DNA clones.
Cytokeratins are a family of polypeptides that form the intermediate-sized filament characteristic of epithelial cells. The cytoskeletons of different types of epithelial cells have been reported to possess specific combinations of the members of this protein family. Therefore, we have sought to examine the correspondence between such differential protein expression and the expression of cytokeratin genes at the nucleic acid level. A library of recombinant plasmids carrying cDNA sequences synthesized from bovine epidermal mRNAs was constructed. Clones of about 10(3) base-pairs coding for all the major epidermal keratins of molecular weights of 50,000, 54,000, 59,000, 60,000 and 68,000 were identified by means of hybridization-selection, followed by one and two-dimensional gel electrophoresis of products of translation in vitro. Under stringent conditions, each of these clones hybridizes specifically with its corresponding mRNA and does not show significant cross-hybridization with mRNAs coding for the other keratins, including those belonging to the same subfamily. Using these clones in RNA blot hybridization analysis, we have studied the expression of keratin genes in diverse bovine epithelial tissues (muzzle epidermis, cornea, esophagus, bladder urothelium, liver) and cultured cell lines from kidney (MDBK) and mammary gland (BMGE + H, BMGE -H). In each case we have found a correlation between the respective keratin polypeptides and the corresponding mRNAs. Whereas mRNA coding for keratins Ia and VIb have been found only in epidermis, genes coding for other epidermal keratins are expressed also in certain non-epidermal epithelia and in cells of the BMGE + H line. In contrast, epidermal keratin mRNA sequences have not been detected in liver or bladder tissue, nor in cultured kidney cells (MDBK) or mammary gland cells of the BMGE - H line, which all express a set of cytokeratin polypeptides entirely different from those of epidermis. In all cases, only one mRNA size species has been found, suggesting that in different cell types the same mRNA species is synthesized from the same keratin gene. We conclude that the mechanisms controlling the cell type-specific synthesis of the diverse keratin genes act at a pre-translational level.


Phycobiliprotein methylation. Effect of the gamma-N-methylasparagine residue on energy transfer in phycocyanin and the phycobilisome.
The phycobiliproteins contain a conserved unique modified residue, gamma-N-methylasparagine at beta-72. This study examines the consequences of this methylation for the structure and function of phycocyanin and of phycobilisomes. An assay for the protein asparagine methylase activity was developed using [methyl-3H]S-adenosylmethionine and apophycocyanin purified from Escherichia coli containing the genes for the alpha and beta subunits of phycocyanin from Synechococcus sp. PCC 7002 as substrates. This assay permitted the partial purification, from Synechococcus sp. PCC 6301, of the activity that methylates phycocyanin and allophycocyanin completely at residue beta-72. Using the methylase assay, two independent nitrosoguanidine-induced mutants of Synechococcus sp. PCC 7942 were isolated that do not exhibit detectable phycobiliprotein methylase activity. These mutants, designated pcm 1 and pcm 2, produce phycocyanin and allophycocyanin unmethylated at beta-72. The phycobiliproteins in these mutants are assembled into phycobilisomes and can be methylated in vitro by the partially purified methylase from Synechococcus sp. PCC 6301. The mutants produce phycobiliproteins in amounts comparable to those of wild-type and the mutant and wild-type phycocyanins are equivalent with respect to thermal stability profiles. Monomeric phycocyanins purified from these strains show small spectral shifts that correlate with the level of methylation. Phycobilisomes from the mutant strains exhibit defects in energy transfer, both in vivo and in vitro, that are also correlated with deficiencies in methylation. Unmethylated or undermethylated phycobilisomes show greater emission from phycocyanin and allophycocyanin and lower fluorescence emission quantum yields than do fully methylated particles. The results support the conclusion that the site-specific methylation of phycobiliproteins contributes significantly to the efficiency of directional energy transfer in the phycobilisome.


miR-21 regulates tumor progression through the miR-21-PDCD4-Stat3 pathway in human salivary adenoid cystic carcinoma.
miR-21, which is a putative tumor onco-miR and frequently overexpressed microRNA in various tumors, has been linked to tumor progression through targeting of tumor-suppressor genes. In this study, we sought to determine whether miR-21 has any role on tumor progression of salivary adenoid cystic carcinoma (SACC) and the possible mechanisms. We found that the level of miR-21 expression was significantly higher in SACC than that in normal salivary tissues, and it is also higher in tumors with metastasis than that without metastasis. Using an anti-miR-21 inhibitor in an in vitro model, downregulation of miR-21 significantly decreased the capacity of invasion and migration of SACC cells, whereas a pre-miR-21 increased the capacity of invasion and migration of SACC cells. To explore the potential mechanisms by which miR-21 regulate invasion and migration, we identified one direct miR-21 target gene, programmed cell death 4 (PDCD4), which has been implicated in invasion and metastasis. The suppression of miR-21 in metastatic SACC-LM cells significantly increased the report activity of PDCD4 promoter and the expression of PDCD4 protein. This subsequently resulted in downregulation of the p-STAT3 protein. The level of miR-21 expression positively related to the expression of PDCD4 protein and negatively related to the expression of p-STAT3 protein in SACC specimens, respectively, indicating the potential role of the STAT3-miR-21-PDCD4 pathway in these tumors. Dysregulation of miR-21 has an important role in tumor growth and invasion by targeting PDCD4. Therefore, suppression of miR-21 may provide a potential approach for the treatment of advanced SACC patients.


Does digital transformation matter to green innovation: based on TOE framework and configuration perspective.
Green innovation is a guarantee for achieving high-quality economic development. However, the complex cause-and-effect relationship between digital transformation and green innovation has not been systematically studied. Digital transformation not only is about technology but also requires organizational and environmental support. Therefore, this study investigates the relationship between digital transformation and green innovation based on the TOE (technology-organization-environment) framework and configuration theory. A fuzzy set qualitative comparative analysis of data from 1948 listed companies reveals that, first, there is no necessary condition that leads to high green innovation, but digital achievements play a more general role in leading to high green innovation; second, three paths to achieve high green innovation are identified. These different configurations indicate multiple paths and complex cause-and-effect relationships to achieve high green innovation. Third, green innovation is a digital technology-based innovation, but in most cases, it also requires organization and environment support. This study can provide some theoretical and practical guidance for enterprises to enhance their green innovation capabilities through digital transformation and promote the achievement of high-quality company development.


Dynamic response of bacterial communities to Microcystis blooms: A three-year study.
Although nutrient availability is widely recognized as the driving force behind Microcystis blooms, identifying the microorganisms that play a pivotal role in their formation is a challenging task. Our understanding of the contribution of bacterial communities to the development of Microcystis blooms remains incomplete, despite the fact that the relationship between Microcystis and bacterial communities has been extensively investigated. Most studies have focused on their interaction for a single year rather than for multiple years. To determine key bacteria crucial for the formation of Microcystis blooms, we collected samples from three sites in the Daechung Reservoir (Chuso, Hoenam, and Janggye) over three years (2017, 2019, and 2020). Our results indicated that Microcystis bloom-associated bacterial communities were more conserved across stations than across years. Bacterial communities could be separated into modules corresponding to the different phases of Microcystis blooms. Dolichospermum and Aphanizomenon belonged to the same module, whereas the module of Microcystis was distinct. The microbial recurrent association network (MRAN) showed that amplicon sequence variants (ASVs) directly linked to Microcystis belonged to Pseudanabaena, Microscillaceae, Sutterellaceae, Flavobacterium, Candidatus Aquiluna, Bryobacter, and DSSD61. These ASVs were also identified as key indicators of the bloom stage, indicating that they were fundamental biological elements in the development of Microcystis blooms. Overall, our study highlights that, although bacterial communities change annually, they continue to share core ASVs that may be crucial for the formation and maintenance of Microcystis blooms.


Marvellous Muscodor spp.: Update on Their Biology and Applications.
Nearly 20 years ago, the first report appeared on the discovery of a novel genus-Muscodor. This organism was isolated as an endophyte from a cinnamon tree that had been introduced to Honduras from Sri Lanka in the early part of the last century. Characteristically, the original Muscodor albus, and all of its species isolated since that time are non-spore producers and each one exudes a characteristic spectrum of volatile bioactive compounds. The majority have a whitish mycelium, which is sometimes coiling, intertwined and decorated with variously shaped structures. Presently, there are at least 22 type species known/documented and each has been described as an endophyte from various plant families with widely varying habitats. An enormous variety of volatile organic compounds (VOCs) are produced by Muscodor spp. and some of these include esters, acids, aldehydes, ketones, aromatics, alkanes, alcohols, nitrosamides and terpenoids. The VOCs are both inhibitory and lethal to a wide variety of fungi and bacteria including some major pathogens of plants and humans. Interestingly, in almost all cases studied, no one compound by itself can mimic the bioactivity of the complete gas mixture, suggesting that the volatiles are acting in a synergistic manner and this has been tested with individual as well as the VOCs in various mixtures and concentrations. This review will discuss some of the recent findings in all aspects of this unique fungal genus whilst at the same time pointing out some of the major questions that remain about its biology, ecology and its applications in agriculture, medicine and other sectors. Most importantly, the authors provide arguments supporting the claim that Muscodor is taxonomically distinct from Induratia, a recently proposed change to its nomenclature.


Draft genome of a clinical Pseudomonas qingdaonensis isolate from a hospitalized patient at Kenyatta National Hospital, Kenya.
The first draft genome of Pseudomonas qingdaonensis, a gram-negative bacteria isolated from hospitalized patients in Kenya, is presented in this study. The genome was assembled using nanopore MinION readings, yielding an assembly of 8,857,650 base pairs made up of 5(five) contigs. The genome sequence of Pseudomonas qingdaonensis will help researchers better grasp its genetics. Furthermore, the data can be a valuable resource for comparative genomics and future research in this novel species.


Goal: "rectangularize" survival; objective: change behavior.
With the technical life span of humans (TLSh) as a foundation, a taxonomy consonant with modern medical science is presented which redefines the chronology of the terms middle-aged, aging, elderly, and aged. This redefinition is one inducer of behavioral change preceding attitudinal change needed to reach the goal: rectangularity of the survival curve. The indivisible triad of nutrition, health, and aging is the principal target for behavioral change at which health professionals can aim their resources during all phases of the life cycle.


Educational inequalities in self-rated health and emotional exhaustion among workers during the COVID-19 pandemic: a longitudinal study.
This study aimed to investigate trends in educational inequalities in poor health and emotional exhaustion during the pandemic among workers, and differences in trends between men and women. Five waves (2019-2021) from the longitudinal study 'the Netherlands Working Conditions Survey COVID-19 study' were used (response rates: 32-38%). Generalized logistic mixed models were used to estimate the changes in absolute and relative educational inequalities in poor health and emotional exhaustion for all workers (n = 12,479) and for men and women, separately. Low and intermediate educated workers reported more often poor health (OR 2.54; 95% CI 1.71-3.77 and OR 2.09; 95% CI 1.68-2.61, respectively) than high educated workers. Intermediate educated women (OR 0.49; 95% CI 0.37-0.64) reported less emotional exhaustion than high educated women, but no differences were observed among men. The prevalence of poor health first decreased across all educational levels until March 2021, and bounced back in November 2021. A similar pattern was found for emotional exhaustion, but for low and intermediate educated workers only. Relative educational inequalities in poor health reduced among men during the pandemic, and absolute differences decreased among men and women by 2.4-2.6%. Relative educational inequalities in emotional exhaustion widened among men only. Absolute differences in emotional exhaustion first increased among both men and women, but narrowed between the last two waves. Socioeconomic inequalities for poor self-rated health remained but narrowed in relative and absolute terms during the pandemic. With regard to emotional exhaustion, socioeconomic inequalities returned to pre-COVID-19 levels at the end of 2021.


Updraft gasification of poultry litter at farm-scale--A case study.
Farm and animal wastes are increasingly being investigated for thermochemical conversion, such as gasification, due to the urgent necessity of finding new waste treatment options. We report on an investigation of the use of a farm-scale, auto-thermal gasification system for the production of a heating gas using poultry litter (PL) as a feedstock. The gasification process was robust and reliable. The PL's ash melting temperature was 639°C, therefore the reactor temperature was kept around this value. As a result of the low reactor temperature the process performance parameters were low, with a cold gas efficiency (CGE) of 0.26 and a carbon conversion efficiency (CCE) of 0.44. The calorific value of the clean product gas was 3.39 MJ m(-3)N (LHV). The tar was collected as an emulsion containing 87 wt.% water and the extracted organic compounds were identified. The residual char exceeds thresholds for Zn and Cu to obtain European biochar certification; however, has potential to be classified as a pyrogenic carbonaceous material (PCM), which resembles a high nutrient biochar.


Association between Bone Mineral Density and Sleep Duration in the Korean Elderly Population.
An association between sleep duration and a wide spectrum of diseases has been reported, but little is known about its relationship with bone mineral density (BMD). Previously conducted studies in Korea and abroad have reported results that are controversial. The present study sought to assess whether sleep duration can be considered an independent risk factor of osteoporosis. We included participants over the age of 60 years with data on self-reported habitual sleep duration and BMD measured with dual X-ray absorptiometry. Comprehensive data on the study sample was obtained from the Korea National Health and Nutritional Survey performed from 2008 to 2010. Sex-stratified multiple regression analyses were conducted with adjustments for possible confounding factors. There was a significant inverse dose-dependent association between sleep duration and BMD measured at total hip, femur neck, and lumbar spine for women and total hip and femur neck for men. Sex-stratified regression analyses adjusted for age and body mass index revealed that sleep duration had a negative correlation with BMD at total hip and femoral neck for both women (β = -0.0048; P = 0.0172 for total hip, β = -0.0037; P = 0.0303 for femur neck) and men (β = -0.0057; P = 0.0218 for total hip, β = -0.0057; P = 0.0143 for femur neck). For women, the significance remained after further adjustment of confounding variables. Prolonged sleep duration appears to have a significant association with lower total hip and femur neck BMD in elderly women but not in elderly men.