A multi-institutional analysis of clinical outcomes and patterns of care of 1p/19q codeleted oligodendrogliomas treated with adjuvant or salvage radiation therapy.
Practice patterns vary for adjuvant treatment of 1p/19q-codeleted oligodendroglioma patients. This study evaluates the outcomes of adjuvant (aRT) versus salvage radiation therapy (sRT) in a multi-institutional cohort. Oligodendroglioma patients with confirmed 1p/19q codeletion who were treated with RT with or without chemotherapy from 2000 to 2017 at four tertiary centers were retrospectively reviewed. Overall survival (OS), post-RT progression-free survival (PFS), freedom-from-RT (FFRT), and radiation necrosis (RN) rates were determined using Kaplan-Meier analyses. OS1/PFS1 were defined from the initial surgery. OS2/PFS2 were defined from the RT start-date. Multivariable analyses (MVAs) of prognostic factors for OS and PFS were performed with Cox regression. One hundred eighty-six patients were identified: 124(67%) received aRT and 62(33%) received sRT; of sRT patients, 58% were observed after surgery while 42% received chemotherapy without aRT. The median time from initial diagnosis to sRT was 61 months, and 74% had reoperations before sRT. sRT had longer OS1 than aRT (94% vs. 69% at 10 years, p = 0.03) and PFS1 (10-year PFS of 80% vs. 68%, p = 0.03), though sRT was not associated with significantly different OS1/PFS1 on MVAs. Chemotherapy did not delay sRT compared to observation and had worse PFS2 (42% vs. 79% at 5 years, p = 0.08). Higher RT dose was not associated with improved clinical outcomes but was associated with higher symptomatic RN rate (15% vs. 0% at 2 years, p = 0.003). Delaying RT for selected oligodendroglioma patients appears safe. Adjuvant chemotherapy does not delay sRT longer than observation and may be associated with worse PFS after RT.


Relationship between rate and extent of absorption of oral theophylline from Uniphyl brand of slow-release theophylline and resulting serum concentrations during multiple dosing.
The relationship between a standardized assessment of rate and extent of absorption of slow-release theophylline and serum concentrations during multiple dosing was examined in eight healthy adult volunteers. Each subject received single doses of a reference theophylline solution in addition to single and multiple doses of Uniphyl, a "once-a-day" theophylline formulation, administered after an overnight fast and after a large breakfast. Extent of absorption was similar during single and multiple dosing but was significantly greater when dose was taken after breakfast; 68 +/- 7% (mean +/- SEM) and 61 +/- 4% of administered doses were absorbed during single and multiple dosing, respectively, when breakfast was withheld, whereas 83 +/- 4% and 86 +/- 4% of administered doses were absorbed when single and multiple doses, respectively, followed breakfast. Observed mean serum concentrations during multiple dosing approximated values predicted from the single-dose study; mean peak serum concentrations averaged more than twice the tough for both predicted and observed values after both fasting and postprandial administration. These data demonstrate incomplete absorption of theophylline from Uniphyl with greater extent of absorption when Uniphyl is taken after food. The study also provides further documentation that characterization of rate and extent of absorption from single doses permit prediction of the mean serum concentration-time profile during multiple dosing at defined rates of theophylline elimination. This provides the potential to anticipate fluctuations in serum concentrations at clinically relevant elimination rates that deviate from the mean of samples typically used for study.


Last Electrically Well: Intraoperative Neurophysiological Monitoring for Identification and Triage of Large Vessel Occlusions.
Intra-operative stroke (IOS) is associated with poor clinical outcome as detection is often delayed and time of symptom onset or patient's last known well (LKW) is uncertain. Intra-operative neurophysiological monitoring (IONM) is uniquely capable of detecting onset of neurological dysfunction in anesthetized patients, thereby precisely defining time last electrically well (LEW). This novel parameter may aid in the detection of large vessel occlusion (LVO) and prompt treatment with endovascular thrombectomy (EVT). We performed a retrospective analysis of a prospectively maintained AIS and LVO database from May 2018-August 2019. Inclusion criteria required any surgical procedure under general anesthesia (GA) utilizing EEG (electroencephalography) and/or SSEP (somatosensory evoked potentials) monitoring with development of intraoperative focal persistent changes using predefined alarm criteria and who were considered for EVT. Five cases were identified. LKW to closure time ranged from 66 to 321 minutes, while LEW to closure time ranged from 43 to 174 min. All LVOs were in the anterior circulation. Angiography was not pursued in two cases due to large established infarct (both patients expired in the hospital). EVT was pursued in two cases with successful recanalization and spontaneous recanalization was noted in one patient (mRS 0-3 at 90 days was achieved in all 3 cases). This study demonstrates that significant IONM changes can accurately identify patients with an acute LVO in the operative setting. Given the challenges of recognizing peri-operative stroke, LEW may be an appropriate surrogate to quickly identify and treat IOS.


[New ESC guidelines 2019 "Diabetes, prediabetes and cardiovascular diseases" : Paradigm shift in reduction of cardiovascular risk in patients with diabetes mellitus].
At the last meeting of the European Society of Cardiology (ESC) in 2019 the new version of the ESC guidelines on "Diabetes, prediabetes and cardiovascular diseases", which were written in collaboration with the European Association for the Study of Diabetes (EASD), were presented. The recommendations of these guidelines included the novel evidence generated over the last 6 years in large cardiovascular outcome trials with novel antidiabetic drugs. This led to a completely novel positioning of medications for lowering blood glucose levels in the reduction of cardiovascular events for patients with diabetes mellitus. This overview article summarizes the most important recommendations of these new guidelines.


Effects of different drying methods on the product quality and volatile compounds of whole shiitake mushrooms.
Various drying methods play important roles in the preservation of foods. However, how the different drying methods affect the quality of some foods is not clear. This paper evaluates the effects of hot air, vacuum, microwave, and microwave vacuum drying techniques on important qualities and volatile compounds of whole shiitake (Lentinus edodes) mushrooms. These four drying methods resulted in a significantly (p<0.05) increase in the content of total free amino acids and the relative content of sulfur compounds of dried products. Microwave vacuum drying helped to maintain larger amounts of taste-active amino acids, and improved nutrient retention and color attributes. Furthermore, the uniform honeycomb network created by microwave vacuum drying along with a less collapsed structure of dried samples can be used to explain the observed high rehydration ratio. Therefore, microwave vacuum drying should be a potential method for obtaining high-quality dried mushrooms.


Chymotrypsin protease inhibitor gene family in rice: Genomic organization and evidence for the presence of a bidirectional promoter shared between two chymotrypsin protease inhibitor genes.
Protease inhibitors play important roles in stress and developmental responses of plants. Rice genome contains 17 putative members in chymotrypsin protease inhibitor (ranging in size from 7.21 to 11.9 kDa) gene family with different predicted localization sites. Full-length cDNA encoding for a putative subtilisin-chymotrypsin protease inhibitor (OCPI2) was obtained from Pusa basmati 1 (indica) rice seedlings. 620 bp-long OCPI2 cDNA contained 219 bp-long ORF, coding for 72 amino acid-long 7.7 kDa subtilisin-chymotrypsin protease inhibitor (CPI) cytoplasmic protein. Expression analysis by semi-quantitative RT-PCR analysis showed that OCPI2 transcript is induced by varied stresses including salt, ABA, low temperature and mechanical injury in both root and shoot tissues of the seedlings. Transgenic rice plants produced with OCPI2 promoter-gus reporter gene showed that this promoter directs high salt- and ABA-regulated expression of the GUS gene. Another CPI gene (OCPI1) upstream to OCPI2 (with 1126 bp distance between the transcription initiation sites of the two genes; transcription in the reverse orientation) was noted in genome sequence of rice genome. A vector that had GFP and GUS reporter genes in opposite orientations driven by 1881 bp intergenic sequence between the OCPI2 and OCPI1 (encompassing the region between the translation initiation sites of the two genes) was constructed and shot in onion epidermal cells by particle bombardment. Expression of both GFP and GUS from the same epidermal cell showed that this sequence represents a bidirectional promoter. Examples illustrating gene pairs showing co-expression of two divergent neighboring genes sharing a bidirectional promoter have recently been extensively worked out in yeast and human systems. We provide an example of a gene pair constituted of two homologous genes showing co-expression governed by a bidirectional promoter in rice.


Products of therapeutic insulins in the blood of insulin-dependent (type I) diabetic patients.
The tendency of insulin in high concentrations to self-associate and the widespread presence of insulin-degrading enzymes suggest that fragments and/or aggregates of insulin may circulate in normal and insulin-dependent diabetic (IDDM) individuals. To examine this possibility, we have analyzed, by sensitive physicochemical methods, immunoreactive insulin (IRI) taken from the blood of 9 healthy volunteers and 12 insulin-dependent diabetic patients. IRI from the blood of the normal volunteers was composed of 6000 (91.0 +/- 1.4%) and 9000 (9.0 +/- 1.4%) molecular weight (mol wt) material. By 10% polyacrylamide disc gel electrophoresis (PAGE) and reverse-phase, high-performance liquid chromatography (HPLC), the 6000 mol wt material was indistinguishable from human insulin standards and insulin fragments were not found. C-peptide reactivity in the 9000 mol wt material confirmed the expected presence of proinsulin and intermediates of proinsulin conversion. IRI harvested from the blood of 12 C-peptide-negative IDDMs, using a variety of insulin preparations, also separated into 6000 (80.5 +/- 3.9%) and 9000-12,000 (19.5 +/- 3.9%) mol wt material. By HPLC, 6000 mol wt IRI was either pork insulin (in volunteers using pure pork insulin) or a mixture of beef (approximately 90%), pork (approximately 10%) and deamidated beef (trace) insulin in those using a beef-pork mixture. However, the 9000-12,000 mol wt material had characteristics entirely distinct from proinsulin of either human or animal origin: C-peptide reactivity was undetectable using any of three sensitive radioimmunoassay systems, on PAGE it migrated more rapidly than proinsulin-like material, and in contrast to proinsulin, it was unaffected by proteolytic degradation.(ABSTRACT TRUNCATED AT 250 WORDS)


Absent right superior vena cava with persistent left superior vena cava which drains to unroofed coronary sinus in a child with atrioventricular septal defect and cor triatriatum sinister: preop correct diagnosis and successful surgery in a single session.
We report a unique case of a 4-year-old boy with intermediate-type atrioventricular septal defect, cor triatriatum sinister, persistent left superior vena cava, unroofed coronary sinus, and absent right superior vena cava. Persistent left vena cava draining into the unroofed coronary sinus was demonstrated easily using the agitated saline-contrast echocardiography. After conformation with angiographic evaluation, surgery was performed at a single session. Roofing of the coronary sinus with polytetrafluoroethylene patch, mitral cleft repair, tricuspid annuloplasty, atrioventricular defect repair with pericardial patch, and resection of the membrane in the left atrium was succeeded without complication.


Is the prognosis of non-hypertensive, COVID-19 patients treated with renin-angiotensin-aldosterone system inhibitors more uncertain?
Previous studies suggested that ongoing treatment with renin-angiotensin-aldosterone system (RAAS) inhibitor drugs may alter the course of SARS-CoV-2 infection and promote the development of more severe forms of the disease. The authors conducted a comparative, observational study to retrospectively analyze data collected from 394 patients admitted to ICU due to SARS-CoV-2 pneumonia. The primary aim of the study was to establish an association between the use of RAAS inhibitor drugs and mortality in the ICU. The secondary aims of the study were to establish an association between the use of RAAS inhibitor drugs and clinical severity at ICU admission, the need for tracheal intubation, total days of mechanical ventilation, and the ICU length of stay. The authors found no statistically significant difference in ICU mortality between patients on RAAS inhibitor drugs at admission and those who were not (31.3% versus 26.2% mortality, p-value 0.3). However, the group of patients taking RAAS inhibitor drugs appeared to be more critical at ICU admission, and this difference became statistically significant in the subgroup of non-hypertensive patients. ICU mortality in the subgroup of non-hypertensive patients treated with RAAS inhibitor drugs also tended to be higher. Overexpression of the angiotensin-converting enzyme 2 (ACE2) in human cells, induced by RAAS inhibitor drugs, promotes viral entry-replication of SARS-CoV-2 and alters the basal balance of the RAAS, which may explain the findings observed in the present study. These phenomena may be amplified in non-hypertensive patients treated with RAAS inhibitor therapy.


Consequences of prolonged sedentary work during the COVID-19 pandemic.
The COVID-19 pandemic has reduced physical activity and increased the time spent sitting. Combined with the lack of ergonomics at home workplaces, the risk of discomfort has increased, especially around the cervical spine and upper limbs. Evaluation of the mentioned problem is the subject of the study. The study used an original questionnaire based on the Nordic Musculoskeletal Questionnaire. The analysis used responses from people who reported discomfort in the form of tingling or numbness in the cervical spine, shoulder, elbow and wrist during the pandemic. Statistical analysis of the results was carried out to formulate conclusions. In addition, individual data were presented as percentages. Considering the working time exceeding 8 hours a day, discomfort in the wrist joint area was most often reported among people working remotely (15.1%). Shoulder complex discomfort was the most common symptom (22%) reported by people working more than 8 hours a day, under the age of 31. In young people, the risk of discomfort in the shoulder, hand and cervical spine area increased. Extended working time is conducive to the appearance of symptoms within the hands. In future studies, it will be necessary to analyze the ergonomic factors responsible for this phenomenon.


Hematopoietic prostaglandin D synthase.
The biological actions of prostaglandin (PG) D(2) include vasodilatation, bronchoconstriction, inhibition of platelet aggregation, and recruitment of inflammatory cells. Characterization of DP receptor null mice in which antigen-induced airway and inflammatory responses are attenuated and identification of CRTH2 as a novel PGD(2) receptor have shed light on the role of PGD(2) in the immune and inflammatory responses. Hematopoietic PGD synthase (H-PGDS) is a cytosolic enzyme that isomerizes PGH(2), a common precursor for all PGs and thromboxanes, to PGD(2) in a glutathione-dependent manner. H-PGDS is expressed in mast cells, antigen-presenting cells, and Th2 cells, and is the only mammalian member of the Sigma class of cytosolic glutathione S-transferases. In this review, we focus on the molecular biology of H-PGDS, the determination of its three-dimensional structure, characterization of the regulation of its gene expression, and information gleaned from transgenic animals.


Validity and reliability of a sensor-enabled intubation trainer: a focus on patient-centered data.
Prior work using simulation for assessing intubation skills has largely focused on the use of observer-generated performance measures in the form of checklists and global ratings scales. The purpose of our work was to investigate whether patient-centered simulation data could be used to quantify learner's performance during direct laryngoscopy. We designed a pretest/posttest prospective intervention study of residents' (n = 25) intubation skills. When assessing validity, all of the patient-centered simulation variables showed significant correlations with the previously validated observer-generated performance measures (r = 0.331-0.463, P ≤ 0.001). When assessing reliability, there were significant correlations between all of the sensor variables, confirming moderate to high inter-item reliability (r = 0.259-0.794, P ≤ 0.05). The observer-generated performance measures showed significant improvement in use of the Macintosh blade (T1 = 2.10/5.00, T2 = 3.64/5.00, P = 0.001). However, this was not the case for the Miller blade (T1 = 1.30/5.00, T2 = 1.75/5.00, P = 0.119). Overall, the patient-centered simulation variables provided a high level of detail regarding performance improvement areas. This study presents a multilevel analysis of sensor-generated simulation data. As the sensors provide sound, formative data regarding patient contact, the outputs may be used for specific criterion measures and detailed performance feedback.


Human mesenchymal stem cells as a gene delivery system to create cardiac pacemakers.
We tested the ability of human mesenchymal stem cells (hMSCs) to deliver a biological pacemaker to the heart. hMSCs transfected with a cardiac pacemaker gene, mHCN2, by electroporation expressed high levels of Cs+-sensitive current (31.1+/-3.8 pA/pF at -150 mV) activating in the diastolic potential range with reversal potential of -37.5+/-1.0 mV, confirming the expressed current as I(f)-like. The expressed current responded to isoproterenol with an 11-mV positive shift in activation. Acetylcholine had no direct effect, but in the presence of isoproterenol, shifted activation 15 mV negative. Transfected hMSCs influenced beating rate in vitro when plated onto a localized region of a coverslip and overlaid with neonatal rat ventricular myocytes. The coculture beating rate was 93+/-16 bpm when hMSCs were transfected with control plasmid (expressing only EGFP) and 161+/-4 bpm when hMSCs were expressing both EGFP+mHCN2 (P<0.05). We next injected 10(6) hMSCs transfected with either control plasmid or mHCN2 gene construct subepicardially in the canine left ventricular wall in situ. During sinus arrest, all control (EGFP) hearts had spontaneous rhythms (45+/-1 bpm, 2 of right-sided origin and 2 of left). In the EGFP+mHCN2 group, 5 of 6 animals developed spontaneous rhythms of left-sided origin (rate=61+/-5 bpm; P<0.05). Moreover, immunostaining of the injected regions demonstrated the presence of hMSCs forming gap junctions with adjacent myocytes. These findings demonstrate that genetically modified hMSCs can express functional HCN2 channels in vitro and in vivo, mimicking overexpression of HCN2 genes in cardiac myocytes, and represent a novel delivery system for pacemaker genes into the heart or other electrical syncytia.


Pacemaker memory data compared to twenty-four-hour holter monitoring in patients with VVI pacemakers and chronic atrial fibrillation.
In light of the results from the AFFIRM trial, the "rate control" strategy has become an accepted treatment modality for patients with atrial fibrillation (AF). Establishing effective rate control requires long-term monitoring of the heart rate. The aim of the study was to compare the heart rate and rhythm monitoring capabilities of the pacemaker memory data (PMD) algorithm and traditional twenty-four-hour Holter monitoring. The study included 55 patients with chronic AF and a permanent VVI pacemaker. The mean and maximum heart rate as well as the percentage of sensed and paced events obtained from the twenty-four-hour Holter were compared with the results retrieved from PMD, started simultaneously. The study was performed over two consecutive days with pacemakers programmed in VVI 40 and 80 bpm mode. Data retrieved from PMD regarding percentage of sensed and paced episodes as well as mean heart rate strongly correlated with data obtained from twenty-four-hour Holter monitoring. The maximum heart rate reported by PMD was significantly higher than that found in the Holter. PMD provides accurate information regarding long-term monitoring of heart rate in patients with AF who have an implanted permanent pacemaker and thus may facilitate optimized drug therapy to achieve rate control of AF.


Inhibition by lactate dehydrogenase-elevating virus of in vivo interleukin 4 production during immunization with keyhole limpet haemocyanin.
Interleukin 4 (IL-4) and gamma interferon (IFN-gamma) gene expression in lymph node cells from mice immunized with keyhole limpet haemocyanin in the presence of complete Freund's adjuvant was analysed by polymerase chain reaction. This immunization clearly induced the expression of IL-4 message, whereas IFN-gamma message was only slightly increased. A concomitant infection with lactate dehydrogenase-elevating virus drastically decreased IL-4 expression whereas IFN-gamma message was not modified. Analysis of the kinetics of cytokine production indicated that the virus did not induce a mere change in the timing of lymphokine production, but a persistent inhibition of IL-4.


A comparison of the metabolic effects of sustained strenuous activity in polar environments on men and women.
This study investigates differences in pre- to post-expedition energy expenditure, substrate utilisation and body composition, between the all-male Spear17 (SP-17) and all-female Ice Maiden (IM) transantarctic expeditions (IM: N = 6, 61 days, 1700 km; SP-17: N = 5, 67 days, 1750 km). Energy expenditure and substrate utilisation were measured by a standardised 36 h calorimetry protocol; body composition was determined using air displacement plethysmography. Energy balance calculation were used to assess the physical challenge. There was difference in the daily energy expenditure (IM: 4,939 kcal day-1; SP-17: 6,461 kcal day-1, p = 0.004); differences related to physical activity were small, but statistically significant (IM = 2,282 kcal day-1; SP-17 = 3,174 kcal day-1; p = 0.004). Bodyweight loss was modest (IM = 7.8%, SP-17 = 6.5%; p > 0.05) as was fat loss (IM = 30.4%, SP-17 = 40.4%; p > 0.05). Lean tissue weight change was statistically significant (IM = - 2.5%, SP-17 = + 1.0%; p = 0.05). No difference was found in resting or sleeping energy expenditure, normalised to lean tissue weight (p > 0.05); nor in energy expenditure when exercising at 80, 100 and 120 steps min-1, normalised to body weight (p > 0.05). Similarly, no difference was found in the change in normalised substrate utilisation for any of the activities (p > 0.05). Analysis suggested that higher daily energy expenditures for the men in Spear-17 was the result of higher physical demands resulting in a reduced demand for energy to thermoregulate compared to the women in Ice Maiden. The lack of differences between men and women in the change in energy expenditure and substrate utilisation, suggests no sex difference in response to exposure to extreme environments.


Effects of melatoninergic agonists on light-suppressed circadian rhythms in rats.
This study addressed the question whether light-suppressed circadian rhythms in cardiovascular parameters in rats could be restored by melatonin and a synthetic analogue. Blood pressure, heart rate, and locomotor activity were monitored by radiotelemetry in six Sprague-Dawley rats. After synchronization to a 12:12 light/dark (LD) schedule (lights on at 0700 hours, 100 lux), rats were kept in constant light (LL) of low intensity (5-10 lux) for 11 weeks. After 3 weeks of LL, rats received daily intraperitoneal (i.p.) injections at 1900 hours of vehicle, the melatonin agonist S-21767 (5 mg/kg) and melatonin (1 mg/kg). Spectral power, 24-h amplitudes and the differences between day and night means were calculated as measures of circadian rhythmicity. During LL a lengthening of the endogenous period to 26 h was observed, which was accompanied by a continuous decrease in circadian amplitude in all parameters monitored until, in the third week of LL, circadian rhythmicity was almost abolished. Neither vehicle, S-21767 nor melatonin were able to restore circadian rhythms in blood pressure and locomotor activity. In contrast, both agonists induced circadian rhythmicity in heart rate in two out of six rats. The day/night difference in heart rate of all animals was significantly increased by S-21767 and, to a smaller extent, by melatonin, whereas the circadian amplitude was not affected. In conclusion, melatonin and the synthetic agonist were able to partially synchronize circadian rhythmicity in heart rate during constant light, but could not restore circadian rhythms in blood pressure.


D-allose, an all-cis aldo-hexose, suppresses development of salt-induced hypertension in Dahl rats.
D-allose, an all-cis aldo-hexose, is non-caloric and possesses antioxidant properties. We investigated the effects of oral D-allose supplementation on the development of high blood pressure and the oxidative status in two genetically hypertensive animal models: Dahl salt-sensitive hypertensive (DS) rats and spontaneously hypertensive rats. The systolic blood pressure of DS rats fed a 4% salt diet for 4 weeks significantly increased from 122+/-8 to 161+/-5 mmHg as compared with DS rats fed a normal salt diet (138+/-5 mmHg at 4 weeks), whereas concordant supplementation of D-allose, but not D-glucose, with a dose of 2 g/kg daily to salt-loaded DS rats suppressed the development of high blood pressure (135+/-7 mmHg at 4 weeks), accompanied with decreases in superoxide production in the aorta that was determined by the lucigenin chemiluminescence and dihydroethidium staining. The increases of urinary protein secretion of salt-loaded DS rats were prevented by D-allose supplementation (DS rats fed 0.5% salt, 18.2+/-6.3 mg/day; DS rats fed 4% salt alone, 81.8+/-16.5 mg/day; DS rats fed 4% salt+D-allose, 31.3+/-11.8 mg/day; DS rats fed 4% salt+D-glucose, 85.3+/-20.5 mg/day). On the other hand, D-allose supplementation in spontaneously hypertensive rats had no significant effect on the blood pressure or the aortic superoxide production during the early developing stage of hypertension. These results underscore the role of enhanced oxidative stress in the pathogenesis of high blood pressure development in DS rats, and suggest the possibility of D-allose supplementation for prevention of salt-sensitive hypertension.


A manganese dioxide nanoparticle-bimetallic metal organic framework composite for selective and sensitive detection of vitamin D3 in human plasma.
For the first time a metal organic framework nanomaterial has been developed comprising manganese dioxide nanoparticle and iron and zinc metal ions interlinked with each other via terephthalic acid. The framework shape was identified as an elongated hexagonal nanorod (TEM) with varying functional groups (FT-IR) and diffraction patterns (XRD). The framework nanocomposite as such in aqueous acidic electrolyte solution has displayed an excellent conductivity (redox behavior) and surface excess (3.08 × 10-8 cm-2). Under the optimized conditions (0.1 M H2SO4 as electrolyte, 50 mV/s scan rate, +1.26 V (vs Ag/AgCl)), the metal organic framework coated electrode has selectively identified vitamin D3 (VD3) in the presence of various other interfering molecules and displayed excellent limit of detection (1.9 ng mL-1). The developed sensor has been applied to the determination of VD3 in extracted human plasma samples (RSD of 0.3-2.6 % and recovery of 96-102 %), and the obtained VD3 values are similar to HPLC-UV method.


Ejaculatory and postejaculatory behavior of male and female rats: effects of sex hormones and electric shock.
Ejaculatory patterns were observed in normally reared, postpuberally castrated male and female rats treated with sex hormones and electrical shock in adulthood. In a preliminary experiment, 3 females treated with 50 microgram estradiol benzoate (EB) and 500 microgram progesterone (P) showed intromission and ejaculatory behavior when subjected to shock. Refractory periods were abnormally short and there was almost no postejaculatory vocalization. In Experiment 1, males and females were tested with electrical shock following daily treatment with 32 microgram EB with and without 500 microgram P on the test day. There was no difference between males and females in preejaculatory behavior, but females displayed abbreviated refractory periods and no postejaculatory vocalization. Progesterone had no observed effect. In Experiment 2 castrated males and females were subjected to shock after treatment with 8 microgram EB per day for 3 weeks. No P was given. Again females showed drastically reduced refractory periods and little vocalization. In Experiment 3, males and females treated with TP and shock displayed ejaculatory patterns, normal refractory periods and vocalization. Results show that female rats are capable of exhibiting the ejaculatory response without sex hormone treatment in perinatal life or androgen treatment in adulthood. It was also demonstrated that there is a sex difference in the postejaculatory behavior shown by estrogen-treated male and female rats.


Function of the anal sphincters following colo-anal anastomosis.
Developments in sphincter-saving operations for carcinoma of the rectum have led to renewed interest in the function of the pelvic floor muscles and the anal sphincters. Twelve patients with a colo-anal anastomosis have been investigated physiologically with reference to sphincter function. It has been shown that the rectum is not essential for the appreciation of impending evacuation, nor for the sphincter inhibitory reflexes, which in this study were elicited by balloon distension above the anastomosis.


Nanoharvesting of bioactive materials from living plant cultures using engineered silica nanoparticles.
Plant secondary metabolites are valuable therapeutics not readily synthesized by traditional chemistry techniques. Although their enrichment in plant cell cultures is possible following advances in biotechnology, conventional methods of recovery are destructive to the tissues. Nanoharvesting, in which nanoparticles are designed to bind and carry biomolecules out of living cells, offers continuous production of metabolites from plant cultures. Here, nanoharvesting of polyphenolic flavonoids, model plant-derived therapeutics, enriched in Solidago nemoralis hairy root cultures, is performed using engineered mesoporous silica nanoparticles (MSNPs, 165 nm diameter and 950 m2/g surface area) functionalized with both titanium dioxide (TiO2, 425 mg/g particles) for coordination binding sites, and amines (NH2, 145 mg/g particles) to promote cellular internalization. Intracellular uptake and localization of the nanoparticles (in Murashige and Skoog media) in hairy roots were confirmed by tagging the particles with rhodamine B isothiocyanate, incubating the particles with hairy roots, and quenching bulk fluorescence using trypan blue. Nanoharvesting of biologically active flavonoids was demonstrated by observing increased antiradical activity (using 2,2-diphenyl-1-picrylhydrazyl radical scavenging assay) by nanoparticles after exposure to hairy roots (indicating general antioxidant activity), and by the displacement of the radio-ligand [3H]-methyllycaconitine from rat hippocampal nicotinic receptors by solutes recovered from nanoharvested particles (indicating pharmacological activity specific to S. nemoralis flavonoids). Post-nanoharvesting growth suggests that the roots are viable after nanoharvesting, and capable of continued flavonoid synthesis. These observations demonstrate the potential for using engineered nanostructured particles to facilitate continuous isolation of a broad range of biomolecules from living and functioning plant cultures.


Comparative kinetic desorption of 60Co, 85Sr and 134Cs from a contaminated natural silica sand column: influence of varying physicochemical conditions and dissolved organic matter.
In order to determine the mechanisms of the retention of 60Co, 85Sr and 134Cs in natural silica sand columns, desorption experiments were performed by changes of pH and ionic strength and by injection of natural organic matter (NOM). Injection of KCl (0.1 M) resulted in a high release of 60Co (60-100%) and 85Sr (72-100%) but a smaller release of 134Cs (31-66%). Only limited release of 60Co (66%) and 85Sr (71%) and no release of 134Cs were observed by injection of NOM. The different percentages of desorption were related to the chemical characteristics of the organic colloids previously retained in columns before the desorption step. The results evidenced different sorption processes on energetically heterogeneous surface sites. According to the initial conditions, the binding of the radionuclides to the solid phase resulted from weak and easily reversible sorption processes to strong association probably by inner sphere complexes. The rather weak release of 134Cs by KCl was attributed to the strong retention of 134Cs by clay coatings on the natural silica sand surfaces.


Sustained insulin-induced remissions of juvenile diabetes by means of an external artificial pancreas.
Remission of diabetes was attempted in 12 recent acute onset ketosis-prone juvenile diabetes after short term (5 +/- 1 days) but excellent blood glucose control by the external artificial beta-cell. The comparison group comrised patients undergoing traditional treatment (n = 28). Nine (75%) persistent (over 3-14 months of duration) although partial (oral drugs required) remissions were obtained in the former group as compared to 3 (11%) in the latter group (p less than 0.05). Cases which showed remissions after insulin infusion had a plasma insulin response to IV glucagon still present before insulin infusion, and a daily urinary C-peptide excretion significantly enhanced after (p less than 0.01). Urinary C-peptide/blood glucose remained improved during the remission period. Thus, early effective treatment by means of the artificial pancreas may break the vicious circle hyperglycaemia-insulin depletion-hyperglycaemia and lead to frequent and sustained remissions of juvenile diabetes.


Subcutaneous administration of hepatitis B immune globulin in combination with lamivudine following orthotopic liver transplantation: effective prophylaxis against recurrence.
Prophylaxis against recurrent hepatitis B virus (HBV) infection with hepatitis B immune globulin (HBIG), in combination with antiviral agents such as lamivudine, has allowed transplantation for this condition to become feasible and accepted. Current protocols allow for HBIG administration either intravenously or intramuscularly. To date, there has been no reported experience with the subcutaneous route of post-transplant HBIG delivery. We report our experience of a 60-yr-old man for whom liver transplantation was performed for chronic HBV. HBIG was administered intramuscularly during the anhepatic phase of surgery. The finding of a portal vein thrombosis requiring repeated thrombectomy necessitated chronic anticoagulation. Post-operatively, HBIG was administered subcutaneously, in four separate injections, for a daily dose of 2170 IU along with continued lamivudine dosing. Hepatitis B surface antibody (anti-HBs) titres reached a serum concentration of >500 IU/L by seven d post-transplant and approximately 1000 IU/L by nine d post-transplant. Five months post-transplant, with continued combination of subcutaneous HBIG and lamivudine, there has been no recurrent HBV infection and anti-HBs titres have been at target levels. Our experience suggests that subcutaneous delivery of HBIG may be a feasible consideration when intramuscular/intravenous dosing is not possible.


Reconstitutions of plasmid partition systems and their mechanisms.
Bacterial plasmid and chromosome segregation systems ensure that genetic material is efficiently transmitted to progeny cells. Cell-based studies have shed light on the dynamic nature and the molecular basis of plasmid partition systems. In vitro reconstitutions, on the other hand, have proved to be an invaluable tool for studying the minimal components required to elucidate the mechanism of DNA segregation. This allows us to gain insight into the biological and biophysical processes that enable bacterial cells to move and position DNA. Here, we review the reconstitutions of plasmid partition systems in cell-free reactions, and discuss recent work that has begun to challenge long standing models of DNA segregation in bacteria.


Synthesis of 5-thiomannose-containing oligomannoside mimics: binding abilities to concanavalin A.
5-Thiomannose-containing oligomannoside mimics, 5SMan alpha(1,6)Man, 5SMan alpha(1,3)Man, 5SMan alpha(1,6)¿Man alpha(1,3)Man¿, Man alpha(1,6)¿5SMan alpha(1,3)Man¿, and 5SMan alpha(1,6)¿5SMan alpha(1,3)Man¿, were synthesized. Dissociation constants for the binding of these mimics to concanavalin A (ConA) were determined by a fluorescence anisotropy inhibition assay. Comparison of these data with those of the natural oligomannosides and with a crystal structure of the trimannoside-ConA complex established that replacing a ring oxygen atom with a sulfur atom causes about 1 kcal/mol decrease in the binding free energy when the ring oxygen is recognized with a hydrogen bonding.


Inhibition of anti-hapten antibody plaque-forming cells by a chemically reactive hapten.
The ability of the chemically reactive hapten 2-4-6-trinitrobenzene sulphonic acid (TNBSA) to inhibit anti-TNP IgM antibody plaque-forming cells (APFC) was investigated. TNBSA at a concentration of 1 mg (3 X 10(-3)M) to 0.3 mg (10(-3] completely inhibited IgM anti-TNP APFC after a 10-min incubation period at 37 degrees C. This inhibition was specific and did not alter the antifluorescein IgM antibody response. After a 24-h culture period in tissue culture medium without antigen, the non-dividing APFC remained inhibited, whereas the dividing APFC escaped this inhibition.


A computational theory for movement pattern recognition based on optimal movement pattern generation.
We have previously proposed an optimal trajectory and control theory for continuous movements, such as reaching or cursive handwriting. According to Marr's three-level description of brain function, our theory can be summarized as follows: (1) The computational theory is the minimum torque-change model; (2) the intermediate representation of a pattern is given as a set of via-points extracted from an example pattern; and (3) algorithm and hardware are provided by FIRM, a neural network that can generate and control minimum torque-change trajectories. In this paper, we propose a computational theory for movement pattern recognition that is based on our theory for optimal movement pattern generation. The three levels of the description of brain function in the recognition theory are tightly coupled with those for pattern generation. In recognition, the generation process and the recognition process are actually two flows of information in opposite directions within a single functional unit. In our theory, if the input movement trajectory data are identical to the optimal movement pattern reconstructed from an intermediate representation of some symbol, the input data are recognized as that symbol. If an error exists between the movement trajectory data and the generated trajectory, the putative symbol is corrected, and the generation is repeated. In particular, we present concrete computational procedures for the recognition of connected cursive handwritten characters, as well as for the estimation of phonemic timing in natural speech. Our most important contribution is to demonstrate the computational realizability for the 'motor theory of movement pattern perception': the movement-pattern recognition process can be realized by actively recruiting the movement-pattern formation process. The way in which the formation process is utilized in pattern recognition in our theory suggests a duality between movement pattern formation and movement pattern perception.


Early and long-term effect of the treatment with pyridostigmine in patients with GMPPB-related congenital myasthenic syndrome.
GMPPB mutations cause congenital myasthenic syndromes (CMS) overlapping with muscular dystrophy. Treatment with pyridostigmine has been reported to be effective in those patients. Nevertheless, results of functional motor assessments to determine its precise impact on the short and long term were not available. We describe the response to treatment with pyridostigmine in three siblings with GMPPB-related CMS using functional motor scales performed regularly over a period of 40 months. The beneficial effect of the treatment was outstanding within the first hours, with all the scales showing a dramatic increase in only two days. This remarkable improvement remained steady during 12 months but a moderate decrease was subsequently detected in two of the three patients. Despite this decline in the scores of the scales at the end of follow up, the functional motor status of the patients was still significantly better than it was before starting treatment. The introduction of pyridostigmine at an early age of the disease in one of the patients, before the onset of scoliosis, may have had a protective effect on it.


Prognostic value of star-shaped intense uptake of 131I in thyroid cancer patients.
After 131I treatment in patients with differentiated thyroid carcinoma (DTC), we sometimes find a star-shaped intense uptake of 131I on therapeutic whole body scans (Rx-WBS), called star artifacts. Therefore, we analyzed the relevant clinical factors and prognostic value of star artifacts in DTC patients. 809 DTC patients who received 131I treatment were retrospectively evaluated and divided into 2 groups of patients with and without star artifacts. We evaluated the therapeutic response which was divided into excellent response (ER), biochemical incomplete response (BIR), indeterminate response (IR), and structural incomplete response (SIR). Clinical factors for the presence of star artifacts were analyzed. We also compared the rate of ER, BIR, IR, SIR and recurrence rate between group 1 and group 2. The major clinical factors included stimulated thyroglobulin (sTg)>1.8ng/ml, 24h radioiodine uptake (RAIU)>2.2%, and positive 99mTcO4- thyroid imaging for the presence of star artifacts. In patients with sTg levels>10ng/ml, patients in group 1 had a higher rate of ablation success and ER than patients in group 2 (80.2% vs 65.6%, P=0.038, 31.6% vs 13.1%, P=0.008, respectively) and had a similar rate of BIR, IR, SIR. Recurrence rate was similar between group 1 and group 2 (5.2% vs 3.1%, P=0.13). More remnant thyroid tissue is one of the factors associated with the presence of star artifacts on Rx-WBS. Patients with star artifacts exhibit a better therapeutic response (ER) when sTg levels are >10ng/ml. However, star artifacts have no effect on the recurrence rate.


Intra-operative identification of a temporal bone fracture line during cochlear implant surgery: a case report.
Temporal bone fractures are divided into otic capsule sparing and otic capsule involving fractures. In the latter, hearing loss, facial nerve paralysis, cerebrospinal fluid leak and meningitis have been reported to occur. The impact of hearing loss can be devastating, especially when occurring in children, with significant risk to speech development and sound localization. In the event of hearing loss, early rehabilitation is therefore of paramount importance. Identification of an intra-operative fracture line with available images and the outcome of such cases has not been reported. We present the case of a 31-month-old male with an otic capsule involving temporal bone fracture, who presented with ipsilateral profound hearing loss. After all required work-up had been performed, he was admitted for a cochlear implant insertion. Per- operatively, a clear fracture line was seen at the round window niche, but a normal insertion was performed despite the anticipated potential ossification at the fracture line. The dreaded complications of cerebrospinal fluid otorrhea or non-auditory stimulation post-implant did not occur. The peculiarity of this case was its rarity, which was demonstrated by clear images that showed the fracture line on preoperative imaging and intraoperatively. Cochlear implantation in the presence of a visible fracture line is feasible and the surgical procedure must not be aborted at its discovery. In these cases, post-operative bacterial meningitis can occur and should be treated aggressively with systemic antibiotics to avoid contralateral ossification of the labyrinth due to labyrinthitis.


Randomized study of antiseptic application technique in healthy volunteers before vascular access insertion (TApAS trial).
In France about 32% of hospitalized patients have a vascular access placement. However, a common complication associated with these is catheter-related bloodstream infection (CRBI) due to the introduction of microorganisms from the skin during catheter insertion. There is no consensus on the best way to clean the skin prior to catheter insertion, which could be a key element of CRBI prevention. The two techniques most commonly used to apply antiseptic to the skin are the concentric circle and back-and-forth techniques, but these have not been compared in clinical trials. Hence, this study conducted this comparison. This single-center, non-comparative, randomized, matched pilot study investigated the levels of cutaneous microorganisms before and after antiseptic application using both techniques in a population of healthy French volunteers. The two application methods were used on each participant's arms at the elbow fold, with randomization for the application side (right or left). Quantification of cutaneous microorganisms was performed in a blinded manner with regard to the technique used. From April 8 to July 17, 2019, 132 healthy volunteers participated in the study. For the whole study population, the mean initial colonization level was 2.68 log10 colony forming units (CFU)/mL (SD 0.82) before the back-and-forth technique, and 2.66 log10 CFU/mL (SD 0.85) before the concentric circle technique. The mean differences in number of microorganisms between the initial sample and the final sample were 2.45 log10 CFU/mL (95% CI: 2.29 to 2.61) for the back-and-forth technique and 2.43 log10 CFU/mL (95% CI: 2.27 to 2.59) for the concentric circle technique. The mean difference in reduction in microorganisms between the back-and-forth technique and the concentric circle technique was 0.02 log10 CFU/mL (95% CI: -0.11 to 0.15). There was no clinically difference in reduction of microorganisms between the concentric circle and back-and-forth techniques at the bend of the healthy volunteer's elbow, after the 30 s of drying of the antiseptic. These findings have a significant impact on time required to achieve antiseptic application before catheter insertion because there is yet no argument to justify application for 30 s, because a single concentric circle pass was much faster with similar results. Future studies should investigate the impact of skin application technique on the prevention of infectious risk associated with catheter insertion on admission to health care facilities (conventional, outpatient, or emergency) and throughout the period of stay in a health care facility.


Study protocol of a randomized controlled clinical trial investigating the effects of omega-3 supplementation on endothelial function, vascular structure, and metabolic parameters in adolescents with type 1 diabetes.
Type 1 diabetes is a main health burden with several related comorbidities. It has been shown that endothelial function, vascular structure, and metabolic parameters are considerably disrupted in patients with type 1 diabetes. Omega-3 as an adjuvant therapy may exert profitable effects on type 1 diabetes and its complications by improving inflammation, oxidative stress, immune responses, and metabolic status. Because no randomized clinical trial has examined the effects of omega-3 consumption in children and adolescents with type 1 diabetes; the present study aims to close this gap. This investigation is a randomized clinical trial, in which sixty adolescents with type 1 diabetes will be randomly assigned to receive either omega-3 (600 mg/day) or placebo capsules for 12 weeks. Evaluation of anthropometric parameters, flow-mediated dilation (FMD) as an endothelial function marker, carotid intima-media thickness (CIMT) as a vascular structure marker, proteinuria, biochemical factors including glycemic and lipid profile, blood urea nitrogen (BUN), creatinine, high-sensitivity C-reactive protein (hs-CRP), and erythrocyte sedimentation rate (ESR), as well as blood pressure will be done at the baseline and end of the trial. Also, dietary intake and physical activity will be assessed throughout the study. Statistical analysis will be performed using the SPSS software (Version 24), and P < 0.05 will be considered statistically meaningful. It is hypothesized that omega-3 supplementation may be beneficial for the management of type 1 diabetes and its complications by reducing inflammation and oxidative stress and also modulating immune responses and glucose and lipid metabolism through various mechanisms. The present study aims to investigate any effect of omega-3 on patients with type 1 diabetes. This trial received approval from Medical Ethics Committee of Iran University of Medical Sciences, Tehran, Iran (IR.IUMS.REC.1400.070). Iranian Registry of Clinical Trials IRCT20210419051010N1 . Registered on 29 April 2021.


Observation of gapped Dirac cones in a two-dimensional Su-Schrieffer-Heeger lattice.
The Su-Schrieffer-Heeger (SSH) model in a two-dimensional rectangular lattice features gapless or gapped Dirac cones with topological edge states along specific peripheries. While such a simple model has been recently realized in photonic/acoustic lattices and electric circuits, its material realization in condensed matter systems is still lacking. Here, we study the atomic and electronic structure of a rectangular Si lattice on Ag(001) by angle-resolved photoemission spectroscopy and theoretical calculations. We demonstrate that the Si lattice hosts gapped Dirac cones at the Brillouin zone corners. Our tight-binding analysis reveals that the Dirac bands can be described by a 2D SSH model with anisotropic polarizations. The gap of the Dirac cone is driven by alternative hopping amplitudes in one direction and staggered potential energies in the other one and hosts topological edge states. Our results establish an ideal platform to explore the rich physical properties of the 2D SSH model.


Skeletal metastasis: the effect on the immature skeleton.
The unique opportunity to study the entire appendicular skeleton of a child who died from metastatic angiosarcoma allowed detailed assessment of radiographically evident involvement. Virtually every portion of the appendicular skeleton had evidence of metastatic disease. However, the extent of involvement was extremely variable, especially when contralateral regions were assessed. The most likely region of metastasis, the metaphysis, is normally a fenestrated cortex of woven bone in the young child, rather than a well demarcated cortex formed by osteon (lamellar) bone, as it is in the adult. The pattern of destruction is such that less extensive areas may be involved before becoming radiographically evident, and trabecular bone involvement may be evident even without cortical damage. The metaphyseal metastatic spread supports the concept of arterial hematogenous dissemination, comparable to osteomyelitis in the child. Pathologic metaphyseal fractures involved both proximal humeri; the fracture also extended along a portion of the metaphyseal-physeal interface in one humerus. In one distal femur the physis readily separated from the metaphysis; this was a non-displaced type 1 growth mechanism injury.


Moving forward in fall prevention: an intervention to improve balance among older adults in real-world settings.
We investigated the effectiveness of a group-based exercise intervention to improve balancing ability among older adults delivered in natural settings by staff in local community organizations. The main component of the intervention consisted of biweekly group-based exercise sessions conducted over 12 weeks by a professional, coupled with home-based exercises. In a quasiexperimental design, 10 community organizations working with older adults offered the intervention to groups of 5 to 15 persons concerned about falls, while 7 organizations recruited similar groups to participate in the control arm of the study. Participants (98 experimental and 102 control) underwent balance assessments by a physiotherapist at registration and 3 months later. Eighty-nine percent of participants attended the 3-month measurement session (n=177). A linear regression analysis showed that after adjusting for baseline levels of balance and demographic and health characteristics, the intervention significantly improved static balance and mobility. Structured, group-based exercise programs offered by community organizations in natural settings can successfully increase balancing ability among community-dwelling older adults concerned about falls.


The Expanding World of Human Leishmaniasis.
New Leishmania isolates form a novel group of human parasites related to Leishmania enrietti, with cases in Ghana, Thailand, and Martinique; other relatives infect Australian and South American wildlife. These parasites apparently cause both cutaneous and visceral disease, and may have evolved a novel transmission mechanism exploiting blood-feeding midges.


Bronchoalveolar inflammatory pathophysiology of bronchopulmonary dysplasia.
It has been emphasized that to prevent BPD ultimately, society must prevent high-risk pregnancies that result in very low birthweight infants. This represents a problem of immense magnitude that demands utmost social science attention. While attempting to solve this complex dilemma, however, RDS and BPD continue to represent the major contributors toward infant mortality and morbidity in developed nations. Certainly elucidation of the pulmonary surfactant system coupled with pharmacologic intervention to replete deficiency of this system has represented a tremendous advance in understanding and therapy of neonatal lung injury. One might make the ethical argument, however, that decreasing mortality from RDS with exogenous pulmonary surfactant mandates an equally vigorous effort toward the prevention of BPD. Elucidation of the bronchoalveolar inflammatory response that characterizes the acute aspects of BPD offers a number of novel, therapeutic approaches that are only beginning to be explored. Although exogenous steroids may indeed have a beneficial effect in reducing the incidence and severity of BPD, there are undoubtedly a number of more specific approaches relating to various aspects of pulmonary inflammation that warrant investigation. Unlike ARDS, BPD represents an ideal disease in which to conduct clinical investigations, because individuals at risk for the disease may be identified early, even before the bronchoalveolar inflammatory response is established. Accordingly, prophylactic therapeutic intervention is plausible. Potentially modulation of the pulmonary inflammatory response associated with BPD will offer clinicians an alternative to current empiric, supportive therapy for BPD; namely therapy directed at one aspect of the very molecular basis of BPD pathophysiology.


Synthesis of cluster mannosides via a Ugi four-component reaction and their inhibition against the binding of yeast mannan to concanavalin A.
The Ugi four-component reaction (U-4CR) was utilized to prepare divalent and trivalent cluster mannosides with different scaffolds. The glycoclusters obtained were tested for their relative inhibitory potency against the binding of yeast mannan to concanavalin A by solid-phase enzyme-linked lectin assays (ELLA) using methyl alpha-D-mannopyranoside as a standard. Among them, a divalent mannoside containing aromatic groups showed the strongest binding affinity to concanavalin A.


Ratio between right ventricular longitudinal strain and pulmonary arterial systolic pressure: A novel prognostic parameter in patients with severe tricuspid regurgitation.
In terms of pathophysiology, tricuspid regurgitation (TR), right ventricular function and pulmonary artery pressure are linked to each other. Our aim was to analyze whether the echocardiography-derived right ventricular free wall longitudinal strain/pulmonary artery systolic pressures (RVFWLS/PASP) ratio can improve risk stratification in patients with severe tricuspid regurgitation (TR). In this single-center retrospective study, 250 consecutive patients with severe TR were enrolled from December 2015 to December 2018. Baseline clinical and echocardiographic parameters were collected. Echocardiography-derived TAPSE/PASP and RVFWLS/PASP were evaluated. The primary endpoint was all-cause mortality. Out of 250 consecutive patients, 171 meet inclusion criteria. Patients were predominantly female, with several cardiovascular risk factors and comorbidities. RVFWLS/PASP ≤0.34%/mmHg (AUC 0.68, p < 0.001, sensitivity 70%, specificity 67%) was associated with baseline clinical RV heart failure (p = 0.03). After univariate and multivariate analyses, RVFWLS/PASP, but not TAPSE/PASP, independently correlated with all-cause mortality (HR 0.004, p = 0.02). Patients with RVFWLS/PASP >0.26%/mmHg (AUC 0.74, p < 0.001, sensitivity 77%, specificity 52%) showed higher survival rates (p = 0.02). In addition at 24 months follow-up, the Kaplan-Meyer curves showed patients with RVFWLS >14% & RVFWLS/PASP >0.26%/mmHg had the best survival rate compared to patients without. RVFWLS/PASP is independently associated with baseline RV heart failure and poor long-term prognosis in patients with severe TR.


Impact of policy changes on the provision of naloxone by pharmacies in Ontario, Canada: a population-based time-series analysis.
In June 2016, the Ontario, Canada government implemented the Ontario Naloxone Program for Pharmacies (ONPP), authorizing pharmacists to provide injectable naloxone kits at no charge to all Ontario residents. In March 2018, the program was amended to include intranasal naloxone and remove the requirement to present a government health card to the dispensing pharmacist. We examined whether these changes increased naloxone dispensing through the ONPP. Population-based time-series analysis using interventional autoregressive integrated moving average models. Ontario, Canada. All Ontario residents between 1 July 2016 and 31 March 2020. Monthly rates of pharmacy naloxone dispensing. Overall, 199 484 individuals were dispensed a naloxone kit during the study period. In the main analysis, the rate of pharmacy naloxone dispensing increased by 65.1% following program changes (55.6-91.8 kits per 100 000 population between February 2018 and May 2018; P = 0.01). In subgroup analyses, naloxone dispensing increased among individuals receiving opioid agonist therapy (OAT) (3374.9-7264.2 kits per 100 000 OAT recipients; P = 0.04) among individuals receiving other prescription opioids (192.8-381.8 kits per 100 000 population prescribed opioids; P < 0.01), among individuals with past opioid exposure (134.7-205.6 kits per 100 000 population with past opioid exposure; P < 0.01) and in urban centers (56.2-91.4 kits per 100 000 population; P < 0.01). We did not observe a clear impact on pharmacy-dispensed naloxone to individuals with no or unknown opioid exposure (34.4-39.3 kits per 100 000 population with no/unknown opioid exposure; P = 0.42) and in rural regions (50.4-97.2 kits per 100 000 population; P = 0.09). Changes to the Ontario Naloxone Program for Pharmacies to add intranasal naloxone and remove the requirement to present a government health card appeared to increase pharmacy-based naloxone dispensing uptake in Ontario, Canada, particularly among individuals at high risk of inadvertent opioid overdose.


Wound healing following excimer laser radial keratotomy.
A pulsed excimer laser was used to produce radial keratotomy in vivo in human corneas and the wound healing process was studied. Fluences of 370 mJ/cm2 at a repetition rate of 20 Hz were effective and atraumatic. The wound healing process was remarkably uneventful without an inflammatory or immune reaction apparent at 21 days. Consistent flattening of the cornea was obtained by shallower cuts than with conventional radial keratotomy techniques.


Redescription of the red-striped soft scale, Pulvinaria tenuivalvata (Newstead), with a new synonymy (Hemiptera, Coccomorpha, Coccidae).
The soft scale, Pulvinaria tenuivalvata (Newstead, 1911), is a major pest of sugarcane in Egypt. This paper provides a redescription and illustration of the adult female based on a microscopic study of the morphology of several adult female specimens and of the type series illustrated by De Lotto (1965) on citronella grass from Uganda. Two paratypes of Pulvinaria saccharia De Lotto, 1964 are also studied and the name is placed here as a junior synonym of Pulvinaria tenuivalvata.


Sources and cycling of dissolved organic and inorganic carbon on the northern Qinghai-Tibetan Plateau: Radiocarbon results from Qinghai Lake.
Tibetan Plateau lakes are sensitive to climate variabilities and affect regional temperature, precipitation and ecosystems. In this study, we investigated the concentrations and carbon isotope (14C and 13C) compositions of dissolved organic and inorganic carbon (DOC and DIC) along with the concentrations of major lithologic ions (Na+, Mg2+, K+, Ca2+) and dissolved silicate (DSi) in a large lake, namely, Qinghai Lake, and its seven inflowing rivers on the northeastern Qinghai-Tibetan Plateau of China. Our results revealed large differences in concentrations and isotopic compositions between DOC and DIC, as well as differences in the concentrations of major ions between the rivers and lake. The chemical weathering of carbonate and silicates in the catchments played important roles in controlling the fates of major ions in the rivers. In Qinghai Lake, evaporation resulted in 40-290 times the accumulation of Na+, Mg2+, and K+ observed in the rivers, while biological uptake and precipitation reduced the concentrations of Ca2+ and DSi in the lake by 4-17 times compared with those in the rivers. In addition, the concentrations of DOC and DIC in the lake were 6-7 times those in the rivers. The carbon isotope (δ13C and Δ14C) signatures of DOC and DIC revealed that the rivers transport millennium-aged DOC (1254 ± 316 years) and DIC (1513 ± 857 years), as influenced largely by the chemical weathering of rocks and preaged soil carbon on the plateau. In contrast, in Qinghai Lake, the ages of DOC are significantly younger (684 ± 378 years) than the ages of riverine DOC, as regulated by newly biologically produced modern DOC. Moreover, the DIC ages in Qinghai Lake are all modern, indicating that exchange with atmospheric CO2 is the dominant process controlling the lake DIC. The accumulation and removal of riverine-aged DIC in Qinghai Lake, however, are not well understood, and the unbalanced radiocarbon in lake DIC remains a mystery that needs further study.


Introduction: Female fertility preservation: innovations and questions.
Oocyte and ovarian tissue cryopreservation represents one of the most important advances in the field of reproductive medicine and biology. Preserving a woman's potential for becoming a genetic mother is now possible for numerous diseases that could impair female fertility either by themselves or as a result of their treatments. However, female fertility preservation is still at the pioneering level and is thus often considered an experimental treatment either from a technical standpoint or in the clinical situation in which it is discussed. As a consequence, many ethics issues are raised with fertility preservation treatment in infants, adolescents, and young women.


The cutaneous uptake of atmospheric oxygen contributes significantly to the oxygen supply of human dermis and epidermis.
It has been known since 1851 that atmospheric oxygen is taken up by the human epidermis. The contribution to total respiration is negligible. Until now the significance for the local oxygen supply of the skin has remained unknown. With a newly developed sensor, the oxygen fluxoptode, it has become possible to make local measurements of the transcutaneous oxygen flux (tcJ(O2)). In this study the sensor was calibrated so that absolute values of tcJ(O2) could be reported. At rest, tcJ(O2) was determined on normal, humidified skin on the volar forearm of 20 volunteers of different age groups. In order to evaluate the contribution of the blood flow to the oxygen supply of the skin, tcJ(O2) was recorded at the end of a 5 min suprasystolic occlusion of the forearm. At normal skin surface partial oxygen pressure (163 +/- 9 Torr), tcJ(O2) was 0.53 +/- 0.27 ml O2 min(-1) x m(-2). A 5 min interruption of blood flow resulted in an increase of 9.5 +/- 6.3 % in tcJ(O2). The value of tcJ(O2) was unaffected by the age of the subject. Published data on the oxygen diffusion properties of skin and simulations of intracutaneous profiles of oxygen partial pressure indicated that under these conditions, the upper skin layers to a depth of of 0.25-0.40 mm are almost exclusively supplied by external oxygen, whereas the oxygen transport of the blood has a minor influence. As a consequence, a malfunction in capillary oxygen transport cannot be the initiator of the development of superficial skin defects such as those observed in chronic venous incompetence and peripheral arterial occlusive disease.


A support system for context awareness in a group home using sound cues.
In a group home, caregivers should be aware of the inhabitant's real-time situation. The aim of our study is to facilitate the awareness of an inhabitant's situation by means of enhanced sound cues. We propose an audio notification system that indicates the real-time situation of persons in a group home environment using sound cues instead of visual surveillance. The notification system comprises a prediction and a notification function. The prediction function estimates a person's real-time situation using a Bayesian network and sensed information; the notification function informs recipients of the predicted situation and the confidence level of the prediction by means of sound cues. We use natural sounds as sound cues. As a first step to examine our system in a group home, we conducted operation and performance tests of each unit under a simple test environment. The correct prediction of the subject's situation is approximately 90%; further, it is shown that the sound cues should be selected according to their environmental dependence. The results show that the method is useful for monitoring persons. As future study, we will conduct a field test on an implemented system and improve it for practical use in a group home.


Clinical diagnoses associated with a positive antinuclear antibody test in patients with and without autoimmune disease.
Antinuclear antibodies (ANA) are antibodies present in several autoimmune disorders. However, a large proportion of the general population (20%) also have a positive test; very few of these individuals will develop an autoimmune disease, and the clinical impact of a positive ANA in them is not known. Thus, we test the hypothesis that ANA + test reflects a state of immune dysregulation that alters risk for some clinical disorders in individuals without an autoimmune disease. We performed high throughput association analyses in a case-control study using real world data from the de-identified electronic health record (EHR) system from Vanderbilt University Medical Center. The study population included individuals with an ANA titer ≥ 1:80 at any time (ANA +) and those with negative results (ANA-). The cohort was stratified into sub-cohorts of individuals with and without an autoimmune disease. A phenome-wide association study (PheWAS) adjusted by sex, year of birth, race, and length of follow-up was performed in the study cohort and in the sub-cohorts. As secondary analyses, only clinical diagnoses after ANA testing were included in the analyses. The cohort included 70,043 individuals: 49,546 without and 20,497 with an autoimmune disease, 26,579 were ANA + and 43,464 ANA-. In the study cohort and the sub-cohort with autoimmune disease, ANA + was associated (P ≤ 5 × 10-5) with 88 and 136 clinical diagnoses respectively, including lupus (OR ≥ 5.4, P ≤ 7.8 × 10-202) and other autoimmune diseases and complications. In the sub-cohort without autoimmune diseases, ANA + was associated with increased risk of Raynaud's syndrome (OR ≥ 2.1) and alveolar/perialveolar-related pneumopathies (OR ≥ 1.4) and decreased risk of hepatitis C, tobacco use disorders, mood disorders, convulsions, fever of unknown origin, and substance abuse disorders (OR ≤ 0.8). Analyses including only diagnoses after ANA testing yielded similar results. A positive ANA test, in addition to known associations with autoimmune diseases, Raynaud's phenomenon, and idiopathic fibrosing alveolitis related disorders, is associated with decreased prevalence of several non-autoimmune diseases.


Delivering resilience training to pre-registration student nurses in partnership with a reservist military organisation: A qualitative study.
Nurses need resilience to safeguard their well-being. In collaboration with a military reservist organisation the Team Series was designed to foster resilience by promoting teamwork and leadership skills in student nurses. To explore participants' experiences of engaging with the Team Series and the skills and knowledge acquired. A qualitative design. A Scottish University. Fourteen 3rd year pre-registration nursing students, ten academic staff and ten reservists. Audio-taped focus groups and interviews thematically analysed. Students conceptualised resilience as clinical competence, valuing an active learning process enabling them to practice clinical and interpersonal skills, utilising a range of communication, team-building, leadership and problem-solving skills. Participation in the Team Series fostered self-awareness and self-confidence, the foundations of resilience, helping students feel more competent in coping effectively in stressful situations. The positive impact of collaborating with a military organisation experienced in developing team-working and leadership skills is demonstrated. Learning experiences designed to promote physical and emotional resilience should be threaded throughout curricula to ensure these attributes are developed and sustained over time.


Work production and work absorption in muscle strips from vertebrate cardiac and insect flight muscle fibers.
Stretch activation, which underlies the ability of all striated muscles to do oscillatory work, is a prominent feature of both insect flight and vertebrate cardiac muscle. We have examined and compared work-producing and work-absorbing processes in skinned fibers of Drosophila flight muscle, mouse papillary muscle, and human ventricular strips. Using small amplitude sinusoidal length perturbation analysis, we distinguished viscoelastic properties attributable to crossbridge processes from those attributable to other structures of the sarcomere. Work-producing and work-absorbing processes were identified in Ca(2+)-activated fibers by deconvolving complex stiffness data. An 'active' work-producing process ("B"), attributed to crossbridge action, was identified, as were two work-absorbing processes, one attributable to crossbridge action ("C") and the other primarily to viscoelastic properties of parallel passive structures ("A"). At maximal Ca(2+)-activation (pCa 5, 27 degrees C), maximum net power output (processes A, B and C combined) occurs at a frequency of: 1.3 +/- 0.1 Hz for human, 10.9 +/- 2.2 Hz for mouse, and 226 +/- 9 Hz for fly, comparable to the resting heart rate of the human (1 Hz, 37 degrees C) and mouse (10 Hz, 37 degrees C) and to the wing beat frequency of the fruit fly (200 Hz, 22 degrees C). Process B maximal work production per myosin head is 7-11 x 10(-21) J per perturbation cycle, equivalent to approximately 2 kT of energy. Process C maximal work absorption is about the same magnitude. The equivalence suggests the possibility that a thermal ratchet type mechanism operates during small amplitude length perturbations. We speculate that there may be a survival advantage in having a mechanical energy dissipater (i.e., the C process) at work in muscles if they can be injuriously stretched by the system in which they operate.


Pseudogene PA2G4P4 promotes oncogene PA2G4 expression and nuclear translocation to affect glioblastoma cell viability and apoptosis.
Dysregulation of pseudogenes is involved in the progression of various types of cancer, including glioblastoma (GBM). Proliferation associated-2G4 (PA2G4) pseudogene 4 (PA2G4P4) has been shown to play an oncogenic role in bladder cancer development. Our study aimed to explore the role and mechanism of PA2G4P4 in GBM progression. PA2G4P4 and PA2G4 expression in GBM tissues was analyzed using the GEPIA database. Cell viability, apoptosis, and activities of caspase-3 and caspase-9 in GBM cells were explored by CCK-8, flow cytometry analysis, and colorimetric activity assay kits, respectively. GEPIA database showed that PA2G4P4 and PA2G4 were both upregulated in GBM tissues. PA2G4P4 expression was also boosted in GBM cells. Knockdown of PA2G4P4 or PA2G4 inhibited cell viability, induced apoptosis, and increased caspase-3 and caspase-9 activities in GBM cells. Data from UALCAN database showed that among top 15 genes correlated with PA2G4P4, PA2G4 had the highest correlation coefficient. Additionally, knockdown of PA2G4P4 inhibited PA2G4 expression and nuclear translocation in GBM cells. Overexpression of PA2G4 abolished the functions of PA2G4P4 knockdown on viability and apoptosis in GBM cells. Summarily, pseudogene PA2G4P4 promotes oncogene PA2G4 expression and nuclear translocation to affect cell viability and apoptosis in GBM cells.


An optical super-microscope for far-field, real-time imaging beyond the diffraction limit.
Optical microscopy suffers from a fundamental resolution limitation arising from the diffractive nature of light. While current solutions to sub-diffraction optical microscopy involve combinations of near-field, non-linear and fine scanning operations, we hereby propose and demonstrate the optical super-microscope (OSM) - a superoscillation-based linear imaging system with far-field working and observation distances - which can image an object in real-time and with sub-diffraction resolution. With our proof-of-principle prototype we report a point spread function with a spot size clearly reduced from the diffraction limit, and demonstrate corresponding improvements in two-point resolution experiments. Harnessing a new understanding of superoscillations, based on antenna array theory, our OSM achieves far-field, sub-diffraction optical imaging of an object without the need for fine scanning, data post-processing or object pre-treatment. Hence the OSM can be used in a wide variety of imaging applications beyond the diffraction limit, including real-time imaging of moving objects.


Androgen dihydrotestosterone promotes bladder cancer cell proliferation and invasion via EPPK1-mediated MAPK/JUP signalling.
The incidence of bladder cancer (BLCA) in men is higher than that in women. Differences in androgen levels between men and women are considered the main causes of incidence rate differences. In this study, dihydrotestosterone (DHT) significantly increased the proliferation and invasion of BLCA cells. In addition, BLCA formation and metastatic rates were higher in N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)-treated male mice than in female and castrated male mice in vivo. However, immunohistochemistry showed that androgen receptor (AR) was expressed at low levels in normal and BLCA tissues of men and women. The classical AR pathway considers that DHT binds to AR and induces it to enter the nucleus, where it functions as a transcription factor. Here, a non-AR combination pathway of androgen that promoted BLCA development was investigated. The EPPK1 protein was bombarded with DHT, as determined by biotinylated DHT-binding pull-down experiments. EPPK1 was highly expressed in BLCA tissues, and EPPK1 knockdown significantly inhibited BLCA cell proliferation and invasion promoted by DHT. Moreover, JUP expression was elevated in DHT-treated high-EPPK1 expressing cells, and JUP knockdown inhibited cell proliferation and invasion. EPPK1 overexpression increased tumour growth and JUP expression in nude mice. Furthermore, DHT increased the expression of the MAPK signals p38, p-p38, and c-Jun, and c-Jun could bind to the JUP promoter. However, the promotion of p38, p-p38, and c-Jun expression by DHT was not observed in EPPK1 knockdown cells, and a p38 inhibitor suppressed the DHT-induced effects, indicating that p38 MAPK may be involved in the regulation of DHT-dependent EPPK1-JUP-promoted BLCA cell proliferation and invasion. The growth of bladder tumours in BBN-treated mice was inhibited by the addition of the hormone inhibitor goserelin. Our findings indicated the potential oncogenic role and mechanism of DHT in BLCA pathogenesis through a non-AR pathway, which may serve as a novel therapeutic target for BLCA.


The application of biosensors for drip loss analysis and glycolytic potential evaluation.
The aim of this study was to evaluate the relationship between glucose and lactate measured by biosensors in drip loss (strip method) with muscle glycolytic potential and their compounds. On the samples taken from Longissimus dorsi of 24 pigs (pure Neckar hybrid line) the following meat quality traits were determined: pH at 24h, meat color according to CIE L(⁎)a(⁎)b(⁎) system and drip loss. The highest correlations were found between glucose in drip loss and glycogen (r=0.84) or glycolytic potential (r=0.81) in muscle. A significant positive relationship between lactate measured in muscle by enzymatic method and by biosensor in drip loss was established (r=0.76). Glycogen, glucose, lactate and glycolytic potential with meat quality traits as ultimate pH, lightness, b(⁎) value and drip loss were significantly related. Results of multiple regression between glucose as well as lactate measured in muscle drip loss with muscle glycolytic potential showed the possibility of its prediction (r=0.87 with Pα≤0.001).


Somatosensory substrates of flight control in bats.
Flight maneuvers require rapid sensory integration to generate adaptive motor output. Bats achieve remarkable agility with modified forelimbs that serve as airfoils while retaining capacity for object manipulation. Wing sensory inputs provide behaviorally relevant information to guide flight; however, components of wing sensory-motor circuits have not been analyzed. Here, we elucidate the organization of wing innervation in an insectivore, the big brown bat, Eptesicus fuscus. We demonstrate that wing sensory innervation differs from other vertebrate forelimbs, revealing a peripheral basis for the atypical topographic organization reported for bat somatosensory nuclei. Furthermore, the wing is innervated by an unusual complement of sensory neurons poised to report airflow and touch. Finally, we report that cortical neurons encode tactile and airflow inputs with sparse activity patterns. Together, our findings identify neural substrates of somatosensation in the bat wing and imply that evolutionary pressures giving rise to mammalian flight led to unusual sensorimotor projections.


Turnover of the actomyosin complex in zebrafish embryos directs geometric remodelling and the recruitment of lipid droplets.
Lipid droplets (LDs), reservoirs of cholesterols and fats, are organelles that hydrolyse lipids in the cell. In zebrafish embryos, the actomyosin complex and filamentous microtubules control the periodic regulation of the LD geometry. Contrary to the existing hypothesis that LD transport involves the kinesin-microtubule system, we find that their recruitment to the blastodisc depends on the actomyosin turnover and is independent of the microtubules. For the first time we report the existence of two distinct states of LDs, an inactive and an active state, that occur periodically, coupled weakly to the cleavage cycles. LDs are bigger, more circular and more stable in the inactive state in which the geometry of the LDs is maintained by actomyosin as well as microtubules. The active state has smaller and irregularly shaped LDs that show shape fluctuations that are linked to actin depolymerization. Because most functions of LDs employ surface interactions, our findings on the LD geometry and its regulation bring new insights to the mechanisms associated with specific functions of LDs, such as their storage capacity for fats or proteins, lipolysis etc.


Parents' and physicians' perceptions of childhood epilepsy.
There is increasing interest in reducing burden of illness in families with childhood epilepsy. Evidence suggests that burden of illness is more related to parents' perception of seizure control than actual seizure control. This study examined the extent to which parents could describe their children's epilepsy and its impact. The degree of concordance between parents' and physicians' perceptions of epilepsy, and its effect on parents' satisfaction with care was also examined. The study involved 37 parents and 1 paediatric neurologist. A questionnaire measured parents' perceptions of seizures and satisfaction with care. A physician questionnaire was piloted for comparison with parent responses. Parents were able to describe and distinguish seizure types, characteristics and impact of epilepsy. Results indicate a low degree of concordance between parents' and physician's perceptions for global, medical and everyday aspects of epilepsy. Preliminary evidence suggests that satisfaction with care may be positively related to degree of concordance. It is feasible to examine burden of illness from the parents' perspective. More attention should be paid to the parent-physician relationship in order for physicians to appreciate parents' perceptions. Future research is needed to replicate the findings in a larger sample of parents and paediatric neurologists.


PIK3CA mutations are associated with pathologic complete response rate to neoadjuvant pyrotinib and trastuzumab plus chemotherapy for HER2-positive breast cancer.
Neoadjuvant treatment with a dual anti-human epidermal growth factor receptor 2 (HER2) blockade with pyrotinib and trastuzumab has been shown to be effective for HER2-positive breast cancer. The genomic characteristics of 425 cancer-related genes from the archived tumour blocks of 50 patients enrolled in a prospective neoadjuvant pyrotinib and trastuzumab plus chemotherapy clinical trial (ChiCTR1900022293) were assessed by next-generation sequencing (NGS). The relationship between tumour biomarkers and the postoperative pathological complete response (pCR) were explored. Forty-five patients completed neoadjuvant chemotherapy and final surgery, of which 26 (58%) achieved a pCR. Among all driver gene mutations, PIK3CA mutation was screened out for having a significant relationship with the treatment response. The pCR rate of patients with wild-type PIK3CA was significantly higher than patients with mutated PIK3CA (80.8% vs. 26.3%; P = 0.00057), and remained significant after a multiple comparison adjustment (Padjusted = 0.024). We further evaluated the predictive value with logistic regression model of clinical features, genetic biomarkers or both, an AUC of 0.912 (95% CI: 0.827-0.997) was achieved in the integrated model. Our data suggest that HER2-positive breast cancers with activating mutations in PIK3CA are less likely to benefit from pyrotinib combined with trastuzumab neoadjuvant therapy.


The impact of age-class and social context on fecal glucocorticoid metabolite levels in free-ranging male giraffes.
One of the primary sources of perceived stress is the social environment of an animal and the interactions with conspecifics. An essential component of the response to a stressor is the activation of the hypothalamic-pituitary-adrenocortical axis, which results amongst others in a temporal increase in circulating glucocorticoid (GC) levels. Giraffes occur in a highly flexible fission-fusion social system and group compositions can change on a daily basis, with bulls establishing an age-related dominance hierarchy and showing a roaming strategy in the search for fertile females. The aim of this study was to non-invasively monitor the influence of different group compositions (mixed sex groups vs. all-male groups) on GC concentrations in free ranging giraffe bulls of different age classes. We collected fecal samples from free-ranging giraffe bulls for 12months in a South African Private Game Reserve to examine age- and social context-related patterns of fecal GC metabolite (fGCM) concentrations. We found that fGCM levels in giraffe bulls are age-class dependent, as well asassociated with changes in the social environment. Independently of the social setting, bulls of the youngest age class exhibited the highest fGCM levels compared to bulls of the other two older age-classes, with differences most pronounced when the bulls are associated in all-male groups. In contrast, an almost reversed picture appears when looking at the fGCM levels of sexually active individuals in mixed sex groups, where highest levels were found for the bulls in the oldest age-class, and the lowest for the bulls in the youngest age-class. The study stresses the importance to taking factors such asage-related status and social settings into account, when interpreting fGCM levels in free ranging giraffes.


SARS-CoV-2 has displaced other seasonal respiratory viruses: Results from a prospective cohort study.
The effect of SARS-CoV-2 on existing respiratory viruses in circulation and the overall burden of viral respiratory disease remains uncertain. Traditionally, severe viral respiratory disease disproportionally affects those with underlying chronic lung diseases. This study aimed to assess the impact of SARS-CoV-2 on the prevalence and clinical characteristics of respiratory virus disease in hospitalised adults. Data for this cohort study were from hospitalised adults who had multiplex PCR testing for respiratory viruses over several seasons in Hampshire, UK. Respiratory virus detection during the first epidemic peak of SARS-CoV-2 was compared to detection during the same time period across previous years. 856 patients had multiplex PCR for respiratory viruses between March and May over 5 years. Before 2020, a non-SARS-CoV-2 virus was detected in 54% patients (202/371) compared to 4.1% (20/485) in 2020 (p < 0.0001). SARS-CoV-2 was associated with asthma or COPD exacerbations in a smaller proportion of infected patients compared to other viruses (1.0% vs 37%, p < 0.0001). The emergence of SARS-CoV-2 was associated with substantial reductions in the circulation of seasonal respiratory viruses and large differences in the characteristics of viral-associated disease, including illness in a greater proportion of patients without underlying lung disease.


Comparison of three different ways of measuring distances between residences and high voltage power lines.
The aim of this study was to evaluate whether distance data based on calculations by use of digitalized geographical information systems (GIS) and distance data based on measurements on 1:5000 maps agree sufficiently with on site distance measurements to be used as input to magnetic field calculations in epidemiological studies. The analysis were performed by use of weighted kappa (kappa(w)) statistical method described by Bland and Altman for comparison of measures of agreement. Map measurements showed better agreement with on site measurements than GIS calculations did. However, we consider both methods appropriate for use in larger epidemiological studies if the results are interpreted with caution. GIS calculations have the advantage of being both time and cost saving.


Modulation of apoptosis and improved redox metabolism with the use of a new antioxidant formula.
Oxidative stress is involved in the pathogenesis of a wide spectrum of diseases, implicating that strategies directed at counterbalancing oxidative processes could have a role in clinical medicine. There is also an evidence that oxidative stress acts as a major determinant of apoptotic cell death. Many studies have reported favourable effects of antioxidant formulas on several parameters of the oxidant-antioxidant balance, but none of them has focused whether antioxidant formulas could modulate apoptosis. We investigated in 20 healthy individuals the effect of supplementation with a formula containing alpha-tocopherol, alpha-lipoic acid, coenzyme Q(10), carnitines, and selenomethionine, on plasma oxidant status and peroxide levels, erythrocyte antioxidant enzymes, lymphocyte apoptosis, and generation of ROS at the mitochondrial level. Control subjects received only carnitines or an incomplete formula with alpha-tocopherol, alpha-lipoic acid, coenzyme Q(10), and selenomethionine. Supplementation with the complete formula resulted in a significant increase in the plasma antioxidant status that was mirrored by a decrease in blood peroxide levels and a reduced generation of ROS at the mitochondrial level. This was associated with a significant decrease in the frequency of peripheral blood lymphocytes, with either CD4 or CD8 phenotype, undergoing apoptosis. Less consistent results were found when either incomplete formula was used. Our study suggests that supplementation with antioxidant formulas can modulate the process of apoptosis under in vivo conditions. The clinical potential of this strategy in the treatment of diseases with an elevated commitment to apoptosis should be explored.


Living in fear: Low-cost avoidance maintains low-level threat.
Excessive avoidance of potential threat is a hallmark of anxiety and is thought to maintain fear by preserving the perceived high-threat value of avoided situations. Previous research has shown that the availability of avoidance maintains low-level threat. Here, we investigated whether an opportunity to engage in avoidance in the presence of a low-threat value safety cue would maintain its perceived threat value when avoidance was unavailable. In a threat conditioning procedure, one conditional danger stimulus (CS+; A+) was followed by an aversive unconditioned stimulus (US; electric shock), and two safety stimuli (CS-; B- and C-) were never followed by the US. Next, clicking a button present during A+ avoided the scheduled US. Avoidance was then made available during C- for participants in the Experimental group but not in the Control group. In the test, all stimuli were presented without the opportunity to avoid. Threat expectancy, eyeblink startle electromyography (EMG), and skin conductance responses (SCRs) were measured. Findings showed an increase in threat expectancy for only C- in the Experimental group during the test phase following avoidance learning to similar levels as during threat conditioning. Compared to the Control group, threat expectancy for both B- and C- remained higher in Experimental group. SCR and startle EMG data did not corroborate these findings. Further research is needed to test the commonly held clinical assumption that avoidance can increase threat value. Low-cost avoidance maintains low-threat value of safety cues.


Predation by three owl species on northern pocket gophers of different body mass.
We examined the estimated sizes of Thomomys talpoides in the diets of Bubo virginianus (1,505 g), Tyto alba (437 g), and Asio otus (245 g) in north-central Oregon between 1973 and 1982. The three owl species tended to consume T. talpoides of different size and responded differently to predicted seasonal body mass changes in the T. talpoides population. On an annual basis B. virginianus preyed upon the largest individuals (x = 67.9 g), whereas A. otus preyed upon the smallest (x = 41.0 g). When compared with the predicted values for the size composition of the T. talpoides population, B. virginianus appeared to prey upon T. talpoides randomly with respect to size, whereas A. out demonstrated a high degree of selectivity, consistently preying upon relatively small individuals. However, the absence of significant seasonal changes in prey size electivities suggests that active choice is not a major factor in predation on gophers by A. otus. Instead, evidence suggests that A. otus attacks T. talpoides randomly with respect to size but captures them in accordance with size-related capture probabilities. Tyto alba preyed most commonly upon intermediate sized T. talpoides (x = 63.3 g), and the presence of T. alba coincided with the seasonal occurrence of T. talpoides of this general size.


Randomized controlled trial protocol to evaluate the effect of an educational intervention using information, motivation and behavioral skills model on sexual satisfaction of new couples in Iran.
Sexual satisfaction is considered as one of the key factors in assessing a person's quality of life and the quality and continuity of marital relationships. According to the results of reports in Iran, many couples are dissatisfied with their sexual lives. Sexuality education is one of the important strategies to prevent early sexual problems and improve sexual satisfaction. The aim of this randomized controlled trial is to compare the efficacy of sexual and marital enrichment package using information, motivation and behavioral skills model on sexual satisfaction of new couples in Iran to routine sexual care program that provided at governmental health centers. This is a randomized, controlled, superiority trial with two parallel groups. One hundred new couples (n = 200) will be recruited and randomized with simple randomization method and a 1:1 allocation. Recruitment will be from governmental health centers and calling on social networks. Couples will be randomized to intervention which will receive Sexual and Marital Enrichment package and control group (routine care at health centers). Couples will be followed up for 4 months. Then primary outcomes (mean score of couples' sexual information, motivation and behavior skills) and secondary outcome (mean score of couples' sexual satisfaction) of study will be measured through the online questionnaire. This trial will be examined the impact of the sexual and marital skills training package tailored to the values and norms governing the sexual life of Iranian couples on their sexual satisfaction. If the trial is effective, its results will be presented to policy makers for implementation at national level. (Iranian Registry of Clinical Trials (IRCT) number): IRCT20181211041926N1. Date of registration: March 2, 2019.


Gaiella occulta gen. nov., sp. nov., a novel representative of a deep branching phylogenetic lineage within the class Actinobacteria and proposal of Gaiellaceae fam. nov. and Gaiellales ord. nov.
Two isolates, with an optimum growth temperature of about 35-37°C and an optimum pH for growth between 6.5 and 7.5, were recovered from a deep mineral water aquifer in Portugal. Strains form rod-shaped cells and were non-motile. These strains were non-pigmented, strictly aerobic, catalase and oxidase positive. Strains F2-233(T) and F2-223 assimilated carbohydrates, organic acids and amino acids. Major fatty acids were novel iso internally branched such as 17:0 iso 10-methyl, 17:0 iso and 15:0 iso 8-methyl. The peptidoglycan contained meso-diaminopimelic acid and menaquinone MK-7 was the major respiratory quinone. Analysis of the 16S rRNA gene shows the strains to cluster with species of the genera Thermoleophilum, Patulibacter, Conexibacter and Solirubrobacter to which they have pairwise sequence similarity in the range 87-88%. Based on 16S rRNA gene sequence analysis, physiological and biochemical characteristics we describe a new species of a novel genus represented by strain F2-233(T) (=CECT 7815(T)=LMG 26412(T)) for which we propose the name Gaiella occulta gen. nov., sp. nov. We also propose that this organism represents a novel family named Gaiellaceae fam. nov. of a novel order named Gaiellales ord. nov.


Inhaled corticosteroid therapy for asthma in preschool children: growth issues.
Although inhaled corticosteroids (ICS) have emerged as the preventive treatment of choice for persistent asthma, few studies have been conducted in infants and very young children that assess the benefits and risks of ICS therapy, particularly with regard to growth. Oral glucocorticoids inhibit growth at multiple levels by blunting pulsatile growth hormone (GH) secretion, decreasing insulin-like growth factor-1 bioactivity, and directly inhibiting new collagen synthesis. Normal childhood growth can be divided conceptually into 3 phases according to primary growth-supporting factors: nutrition-dependent growth of infancy, GH-dependent childhood growth, and sex steroid/GH stimulation of pubertal growth. Susceptibility to glucocorticoid-induced growth suppression appears to increase during periods of transition from one phase to another, particularly in the immediate prepubertal years. Studies using ICS at varying dosages demonstrate the possibility of short-term growth suppression, but long-term studies suggest a negligible effect, if any, on final adult height or bone mineral density. Although certain speculations regarding the safety of ICS use in infants and very young children can be made based on these data, age-specific studies are needed to account for effects of differences in oral versus airway deposition and growth axis resiliency, which may occur in these patients.