Induction of axonal growth by heterophilic interactions between the cell surface recognition proteins F11 and Nr-CAM/Bravo.
F11 and Nr-CAM/Bravo are two axon-associated glycoproteins belonging to different subgroups of the immunoglobulin superfamily. In this report we have investigated the interaction of both proteins using neurite outgrowth and binding assays. Antibody blocking experiments demonstrate that neurite extension of tectal cells on immobilized F11 is mediated by Nr-CAM/Bravo. Binding studies further reveal a direct heterophilic interaction between F11 and Nr-CAM/Bravo. This activity can be mapped to the amino-terminal second or third immunoglobulin-like domain within F11 with domain-specific monoclonal antibodies and deletion mutant proteins expressed on COS cells. Furthermore, perturbation experiments with domain-specific monoclonal antibodies demonstrate that this region is required for adhesion and neurite extension.


Effects of Byakko-ka-ninjin-to on salivary secretion and bladder function in rats.
Byakko-ka-ninjin-to (BN) is a Kampo medicine (traditional Japanese medicine) that is frequently used to treat xerostomia, which is also a side effect of anticholinergic agents such as oxybutynin and propiverine widely used for the treatment of patients with urinary incontinence or frequency. We investigated the effects of BN on salivation and bladder function in rats, in the presence and absence of oxybutynin. Treatment with BN alone resulted in a slight increase in salivary secretions. In contrast, pilocarpine, a known muscarinic agonist, produced a significant increase in salivary secretions that could be blocked by pretreatment with oxybutynin. A single oral dose of BN at 200mg/kg body weight just before oxybutynin treatment resulted in less inhibition by oxybutynin of pilocarpine-induced salivation. However, BN had no effect on the decreased amplitude of bladder contractions that result from oxybutynin administration. These results suggest that BN might be useful for the xerostomia induced by anticholinergic agents, without influencing their beneficial effect on micturition.


On the (melting) rocks: Climate change and the global issue of permafrost depletion.
This short communication reports on the pressures posed by climate change on permafrost. The phenomenon of the (melting) rocks, soil, and ground that host permafrost does not just concern a remote stretch of the Arctic north. It is a far larger area than most citizens may realise if looking at an ordinary map projection. Broadly distributed and crucial as it is for the Earth's climate, permafrost thawing due to climate change can affect or upend several aspects associated with life and prosperity on Earth, demanding far greater attention. The loss of permafrost is a global problem that requires a global solution. Greenhouse gas emissions (GHG) must be reduced to slow permafrost's thawing and negative impacts. As such, this short communication aims to catalyse a global debate on this climate change consequential issue, also providing specific suggestions for reducing the impacts of permafrost depletion.


Chloral hydrate enhances ethanol-induced inhibition of methanol oxidation in mice.
Several studies indicated that chloral hydrate can prolong the disappearance time of ethanol from blood in mice. This seems to result from inhibition of the enzyme alcohol dehydrogenase by chloral hydrate and trichloroethanol, its main metabolite. We examined the effect of both these compounds on the disappearance time of methanol in mice. Also the effect of a combination of ethanol and chloral hydrate on the disappearance time of methanol was examined. Several groups of six mice each received methanol (1 g/kg i.p.) followed immediately by one of the following treatments: saline (10 ml/kg); chloral hydrate (0.4 g/kg); trichloroethanol (0.36 g/kg); ethanol (4 g/kg); or a combination of chloral hydrate (0.2 g/kg) and ethanol (4 g/kg). The concentrations of methanol in blood were measured at 1, 2, 4, and 8 h after its administration and were used to calculate some approximate indicators of methanol elimination in each group. The results show that all the above treatments do prolong the disappearance time of methanol in the blood of mice to varying extents. The ethanol-chloral hydrate combination produced the most pronounced effect.


Suppression of autonomic-mediated triggered firing in pulmonary vein preparations, 24 hours postcoronary artery ligation in dogs.
Rapid arrhythmia originating within pulmonary veins (PVs) precipitates atrial fibrillation (AF) in man. To determine a possible basis for an increased incidence of AF observed peri-myocardial infarction in man, we compared AF induction in vivo and triggered arrhythmia formation within isolated PVs in vitro in normal dogs and dogs studied 24 hours postcoronary artery ligation. The incidence of AF initiated by atrial premature stimuli was increased in dogs postcoronary artery ligation (6/9) versus normal (2/12) (P = 0.03). In isolated PVs from normal hearts, pause-dependent early afterdepolarizations (EADs) were enhanced by catecholamines. Rapid arrhythmia (1,182 +/- 213 beats/min) was triggered during isoproterenol/norepinephrine (32 nM) + acetylcholine (100 nM) (N = 16/23) using the same pacing pauses eliciting EADs. Rapid arrhythmia (802 +/- 161 beats/min) was also triggered by local autonomic nerve stimulation (ANS; N = 18/23). Despite equivalent pause-dependent afterdepolarization formation in PVs from infarcted hearts, a rightward 45-fold and 28-fold shift in the dose-response curve for afterdepolarization enhancement was observed for isoproterenol and norepinephrine, respectively (P < 0.02). ANS (N = 1/19) and isoproterenol/norepinephrine (32 nM) + acetylcholine (100 nM) (N = 0/9 and 0/12, respectively) (P = 0.0001) failed to elicit arrhythmia formation. Beta-adrenergic receptor desensitization was associated with a 2.5-fold increase in PV beta-adrenergic receptor kinase (ARK). The data demonstrate decreased susceptibility of isolated canine PVs for arrhythmia triggered by local ANS, or pacing pauses in the presence of a catecholamine + acetylcholine, postmyocardial infarction, despite a greater susceptibility of the intact heart to AF. The decreased arrhythmia susceptibility was observed coincident with an increase in beta-ARK and a decreased responsiveness to beta-adrenergic receptor agonists.


Neurochemical and functional consequences following 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) and methamphetamine.
The neurochemical and functional consequences following MPTP administration to the rat were evaluated and compared to similar effects following methamphetamine administration. It was observed that MPTP induced long lasting depletions of striatal dopamine concentrations and this neurotoxic effect could be prevented by pargyline pretreatment. The MPTP-induced neuronal damage produced a tolerance to the disruptive effects of amphetamine and a supersensitivity to the disruptive effects of apomorphine in rats responding in a schedule controlled paradigm. Methamphetamine, like MPTP, produced depletions of striatal dopamine but these actions were potentiated by pargyline pretreatment. These observations are discussed in reference to possible deleterious effects following the administration of pargyline to patients with Parkinson's Disease.


Psychological Correlates of Health anxiety in Response to the Coronavirus (COVID-19) Pandemic: a Cross-Sectional Online Study in Iran.
Current models suggest health anxiety as a fundamental variable associated with fear and anxiety related to COVID-19. The investigation was carried out in separate two studies on the Iranian population. The first study aims to test the COVID-19 Anxiety Inventory (N = 202). The findings indicate a two-factor structure of the scale. Participants (N = 1638) completed the online survey anonymously in the second study, including the COVID-19 Anxiety Inventory, Short Health Anxiety Inventory, The Intolerance of Uncertainty Scale, Anxiety Sensitivity Index-3, Body Vigilance Scale, Depression Anxiety Stress Scales 21, and Contamination Cognitions Scale. Results showed that health anxiety, anxiety sensitivity, and body vigilance would significantly contribute to fears of contracting COVID-19. Moreover, the findings support a central role of intolerance of uncertainty in predicting COVID-19 anxiety. The study results provided both theoretical and practical implications for understanding psychosocial predictors during the COVID-19 pandemic.


Spontaneous superficial femoral artery dissection with distal embolization.
Primary arterial dissection of the peripheral vessels is a rare condition. We report a case of spontaneous dissection of the distal superficial femoral artery compounded by distal embolization leading to ischemic symptoms. The patient was successfully treated with exploration of the superficial femoral artery over the area of the dissection, distal embolectomy, and reconstruction by way of an interposition graft. Awareness of this condition leads to potentially earlier diagnosis and expands the therapeutic options.


The economic impact of chronic diseases: how do households respond to shocks? Evidence from Russia.
The epidemiological burden of chronic diseases is increasing worldwide and there is very little empirical evidence regarding the economic impact of chronic diseases on individuals and households. The primary objective of this paper is to explore the evidence on how chronic diseases affect household healthcare expenditure, non-health consumption, labour (earned) income, and to demonstrate how transfers may provide some insurance against shocks from chronic diseases. We have explicated a two-part Heckit model on household level data obtained from the Living Standard Measurement Surveys (LSMS) from Russia to control for nontrivial proportion of zeros in the dependent variables, skewed distribution of expenditure data and endogeneity. The results indicate that chronic diseases are significantly associated with higher levels of household healthcare expenditure in Russia and productivity losses reflected by reduced labour supply and reduced household labour income. Non-healthcare expenditure also increased. Results suggest that households are able to insure non-health consumption against chronic diseases, possibly from transfers, which also increased. In addition, socioeconomic status indicators significantly explained the impact of chronic diseases on households. Insurance and higher average education in households were associated with higher healthcare expenditure. Household transfers were significant in Russia despite an appreciable level of insurance cover. We conclude that households depend on informal coping mechanisms in the face of chronic diseases, irrespective of insurance cover. These results have implications for policies regarding the financing of treatment and control of chronic diseases in the country studied.


Ecological Momentary Assessment of Social Interactions: Associations With Depression, Anxiety, Pain, and Fatigue in Individuals With Mild Stroke.
To examine real-time relationships between social interactions and poststroke mood and somatic symptoms in participants' daily environments. Prospective observational study using smartphone-based ecological momentary assessment (EMA) surveys 5 times a day for 2 weeks. Multilevel models were used to analyze data for concurrent and lagged associations. Community. Adults (N=48) with mild stroke. Not applicable. EMA measures of self-appraisal of social interactions (confidence, satisfaction, and success), as well as mood (depression and anxiety) and somatic (pain and fatigue) symptoms. In concurrent associations, increased depressed mood was associated with reduced ratings of all aspects of social interactions. Fatigue was associated with reduced ratings of social satisfaction and success. In lagged associations, increased anxious mood preceded increased subsequent social confidence. Higher average social satisfaction, confidence, and success were related to lower momentary fatigue, anxious mood, and depressed mood at the next time point. Regarding clinicodemographic factors, being employed was concurrently related to increased social interactions. An increased number of comorbidities predicted higher somatic, but not mood, symptoms at the next time point. This study provides preliminary evidence of dynamic relationships between social interactions and somatic and mood symptoms in individuals with mild stroke. Interventions to not only address the sequelae of symptoms, but also to promote participation in social activities in poststroke life should be explored.


Functional association of Gdown1 with RNA polymerase II poised on human genes.
Most human genes are loaded with promoter-proximally paused RNA polymerase II (Pol II) molecules that are poised for release into productive elongation by P-TEFb. We present evidence that Gdown1, the product of the POLR2M gene that renders Pol II responsive to Mediator, is involved in Pol II elongation control. During in vitro transcription, Gdown1 specifically blocked elongation stimulation by TFIIF, inhibited the termination activity of TTF2, and influenced pausing factors NELF and DSIF, but did not affect the function of TFIIS or the mRNA capping enzyme. Without P-TEFb, Gdown1 led to the production of stably paused polymerases in the presence of nuclear extract. Supporting these mechanistic insights, ChIP-Seq demonstrated that Gdown1 mapped over essentially all poised polymerases across the human genome. Our results establish that Gdown1 stabilizes poised polymerases while maintaining their responsiveness to P-TEFb and suggest that Mediator overcomes a Gdown1-mediated block of initiation by allowing TFIIF function.


Introduction of the Taser into British policing. Implications for UK emergency departments: an overview of electronic weaponry.
The Taser is a development of the stun gun. It has recently been introduced into British policing as a "less lethal" weapon to fill the operational gap between the baton and the gun for controlling potentially dangerous and violent suspects. It is inevitable that "tasered" victims will be brought to hospitals. A review of clinical experience with electronic weaponry is presented. Suggestions for managing "tasered" subjects are provided.


Vasoactive intestinal polypeptide stimulates the secretion of catecholamines from the rat adrenal gland.
1. Our previous studies have indicated that splanchnic nerves release a substance(s), other than acetylcholine, that induces the secretion of catecholamines from the rat adrenal medulla. To identify the nature of the non-cholinergic substance, the effects of met-enkephalin and vasoactive intestinal polypeptide (VIP) were investigated in the perfused adrenal gland of the rat. 2. The secretion of catecholamines increased from a basal level of 8 ng to a maximum value of 18 ng during perfusion with 100 microM-met-enkephalin. The secretion evoked by 10 micrograms acetylcholine increased from 118 to 143 ng in the presence of 10 microM-met-enkephalin. Higher concentrations of met-enkephalin (100 microM) had no additional effect. Secretion of catecholamines evoked by stimulation of splanchnic nerves (10 Hz for 30 s) was even less (8%) affected by met-enkephalin. 3. 0.3 microM-VIP caused a significant increase in the secretion of catecholamines, and the effect increased with an increase in the concentration of VIP. About 115 ng of catecholamines were secreted during 15 min perfusion with 3 microM-VIP. 4. VIP-evoked secretion was not affected by antagonists of nicotinic and muscarinic receptors, nor by chronic splanchnicotomy. However, removal of calcium ions from, and inclusion of 1 mM-EGTA in, the perfusion medium completely inhibited the secretion evoked by VIP. 5. VIP-evoked secretion was reduced (20-75%) in a concentration-dependent manner by 3-30 microM-naloxone. 6. It is suggested that VIP may be the non-cholinergic excitatory substance present in the splanchnic nerves and released along with acetylcholine during simulation of the nerves to evoke secretion of catecholamine from the rat chromaffin cells.


Cytoskeletal organization in the oocyte, zygote, and early cleaving embryo of the stripe-faced dunnart (Sminthopsis macroura).
Ovulation occurs in Sminthopsis macroura approximately 160 hr after administration of 1.3 IU PMSG, and yields significantly more oocytes than does spontaneous ovulation (P = 0.001). Germinal vesicle (GV)-stage oocytes have a thin cortical rim of microfilaments, which is disrupted by exposure to cytochalasin D. After GV breakdown, the first meiotic spindle forms subcortically and parallel to the oolemma. It rotates during anaphase and telophase to extrude the first polar body. This rotation is associated with a local cortical concentration of microfilaments, which is extruded in the first polar body. The second meiotic spindle is orthogonal to the surface, and extrusion of the second polar body is not associated with obvious local changes in cortical actin, resulting in a polar body containing little polymerized actin. The sites of second polar body emission and sperm entry are always in the half of the oocyte opposite the concentrating yolk mass, and are within 60 degrees of each other in most oocytes. During the concentration and eccentric movement of the yolk, microfilaments condense around it. During yolk expulsion, these microfilaments become continuous with those located subcortically. During early cleavage, the cytocortex of the zygote, but not of the extruded yolk mass, stains heavily for polymerised actin. Multiple sites of pericentriolar material are detectable in the cytoplasm of some secondary unfertilized oocytes which, in the presence of taxol, generate large cytasters and pseudospindle structures. After fertilization, a large aster is formed in association with the sperm entry point and serves as the center of an extensive cytoplasmic network of microtubules which surrounds but does not enter the yolk mass. Taxol treatment generates small cytasters within this meshwork and promotes selective stabilization of some periyolk microtubules opposite to the sperm aster.


Defective IL-2 receptor expression in lymphocytes of patients with arsenic-induced Bowen's disease.
The immune function of peripheral mononuclear cells (MNC) in patients with endemic arsenic-induced Bowen's disease (BD) was investigated. Many cytokines and immune-related factors were determined in the present study. Interleukin-1beta and TNF-alpha production was used as an indicator of monocyte/macrophage function. II-2 and sIL-2R production was used as an indicator of lymphocyte activation. The release of sCD4 and sCD8 was used as an indicator of activation of respective T-cell subpopulations. Production of IFN-gamma and IL-2 reflected the cellular effector function of helper T-cells type 1. In vivo cell-mediated immunity was also assessed by estimation of the percentage of T-cells in peripheral blood MNC and the nonspecific delayed-type hypersensitivity (DTH) response to 2,4-dinitrochlorobenzene (DNCB). Both assays revealed depressed cell-mediated immunity in BD. Compared with healthy controls, spontaneous and PHA-induced IFN-gamma and TNF-alpha production was significantly decreased in BD whereas spontaneous release of IL-2, sCD4 and sCD8 was significantly increased. Although PHA stimulation increased IL-2 release, the expression of IL-2R alpha and beta chains and the release of sIL-2R were not proportionately increased in BD. In addition, IL-2-mediated [3H]-thymidine incorporation by MNC in patients with BD was significantly decreased. These findings suggest that the defective cell-mediated immune function in BD is due to impairment of membrane IL-2R expression in lymphocytes after stimulation.


Strategies for Improving Visualization During Endoscopic Skull Base Surgery.
The nasal cavity has a robust vascular supply, and bleeding is a primary obstacle to the minimally invasive skull base technique. Venous bleeding, including the cavernous sinus, can be managed with various techniques using hemostatic materials and pressure. A thorough understanding of the skull base vascular anatomy is vital for avoiding injury to major arteries and having confidence to control venous bleeding to optimize the endoscopic view and tumor resection.


Genotype-phenotype correlation of 33 patients with maple syrup urine disease.
Maple syrup urine disease (MSUD) is a rare autosomal recessive inherited disorder due to defects in the branched-chain α-ketoacid dehydrogenase complex (BCKDC). MSUD varies in severity and its clinical spectrum is quite broad, ranging from mild to severe phenotypes. Thirty-three MSUD patients were recruited into this study for molecular genetic variant profiling and genotype-phenotype correlation. Except for one patient, all other patients presented with the classic neonatal form of the disease. Seventeen different variants were detected where nine were novel. The detected variants spanned across the entire BCKDHA, BCKDHB and DBT genes. All variants were in homozygous forms. The commonest alterations were nonsense and frameshift variants, followed by missense variants. For the prediction of variant's pathogenicity, we used molecular modeling and several in silico tools including SIFT, Polyphen2, Condel, and Provean. In addition, six other tools were used for the prediction of the conservation of the variants' sites including Eigen-PC, GERP++, SiPhy, PhastCons vertebrates and primates, and PhyloP100 rank scores. Herein, we presented a comprehensive characterization of a large cohort of patients with MSUD. The clinical severity of the variants' phenotypes was well correlated with the genotypes. The study underscores the importance of the use of in silico analysis of MSUD genotypes for the prediction of the clinical outcomes in patients with MSUD.


[Effect of diuretics (diacarb and lasix) on the experimental antitumor activity, toxicity and pharmacokinetics of the antibiotic, olivomycin].
Diacarb or lasix in combination with olivomycin increased the antibiotic antiblastomic activity and toxicity when used for the course treatment of mice with transplanted lymphosarcoma LIO-I. The chemotherapeutic indices of such combinations did not differ from those of olivomycin used alone. Diacarb decreased excretion of olivomycin with the urine in healthy mice, while lasix increased it.


Distinct trajectories of long-term symptom severity in pediatric obsessive-compulsive disorder during and after stepped-care treatment.
First-line treatments for pediatric obsessive-compulsive disorder (OCD) include exposure-based cognitive-behavioral therapy (CBT) and selective serotonin reuptake inhibitors (SSRIs). No studies have thus far identified distinct classes and associated predictors of long-term symptom severity during and after treatment. Yet, these could form the basis for more personalized treatment in pediatric OCD. The study included 269 OCD patients aged 7-17 years from the Nordic Long-term OCD Treatment Study (NordLOTS). All participants received stepped-care treatment starting with 14 weekly sessions of manualized CBT. Nonresponders were randomized to either prolonged CBT or SSRIs. Symptom severity was assessed using the Children's Yale-Brown Obsessive-Compulsive Scale at seven time points from pre- to post-treatment and over a three-year follow-up. Latent class growth analysis (LCGA) was performed to identify latent classes of symptom severity trajectories. Univariate and multivariate analyses were used to detect differences between classes and identify predictors of trajectory class membership including several clinical and demographic variables. Nordic Long-term Obsessive-Compulsive Disorder (OCD) Treatment Study; www.controlled-trials.com; ISRCTN66385119. Three LCGA classes were identified: (a) acute, sustained responders (54.6%); (b) slow, continued responders (23.4%); and (c) limited long-term responders (21.9%). Class membership was predicted by distinct baseline characteristics pertaining to age, symptom severity, contamination/cleaning and anxiety symptoms. The LCGA suggests three distinct trajectory classes of long-term symptom severity during and after treatment in pediatric OCD with different clinical profiles at pretreatment. The results point to required clinical attention for adolescent patients with contamination/cleaning and anxiety symptoms who do not show convincing responses to first-line treatment even though they may have reached the established cutoff for treatment response.


Headache, Opiate Use, and Prescribing Trends in Women With Idiopathic Intracranial Hypertension: A Population-Based Matched Cohort Study.
Physician prescribing habits for opiates and headache therapies have not been previously evaluated in a large, matched cohort study in idiopathic intracranial hypertension (IIH). Our objective was to evaluate opiate and headache medication prescribing habits in women with IIH compared to matched women with migraine and population controls. We also investigated the occurrence of new onset headache in IIH compared to population controls. We performed a population-based matched, retrospective cohort study to explore headache outcomes. Cross-sectional analyses were used to describe medication prescribing patterns. We used data from IQVIA Medical Research Data, an anonymized, nationally representative primary care electronic medical records database in the United Kingdom, from 1st January 1995 to 25th September 2019. Women aged ≥16 years were eligible for inclusion. Women with IIH (exposure) were matched by age and body mass index with up to 10 control women without IIH but with migraine (migraine controls), and without IIH or migraine (population controls). 3411 women with IIH, 13,966 migraine controls and 33,495 population controls were included. The adjusted hazard ratio (aHR) for new onset headache in IIH compared to population controls was 3.09 (95%CI 2.78-3.43). In the first year after diagnosis, 58% of women with IIH were prescribed acetazolamide and 20% topiramate. 20% of women with IIH were prescribed opiates within the first year of their diagnosis, reducing to 17% after six years, compared to 8% and 11% among those with migraine, respectively. Twice as many women with IIH were prescribed opiates compared to migraine controls and three times as many women with IIH were prescribed opiates compared to population controls. Women with IIH were also prescribed more headache preventative medications compared to migraine controls. Women with IIH were more likely to be prescribed opiate and simple analgesics compared to both migraine and population controls. Women with IIH trialled more preventative medications over their disease course suggesting that headaches in IIH may be more refractory to treatment.


A low-cost alternative for nasolaryngoscopy simulation training equipment: a randomised controlled trial.
Flexible nasolaryngoscopy is a key diagnostic procedure used in many specialities. Simulation-based teaching is beneficial for endoscopy training, but it is expensive. This study assessed whether an inexpensive simulation model is an effective training method for flexible nasolaryngoscopy. A three-armed, randomised, controlled trial was performed. One group received no simulation training, while two others were trained with either a high-cost or a low-cost model. All candidates then performed flexible nasolaryngoscopy on a volunteer. Their ability to perform this task was assessed by the patient discomfort score and time taken by a blinded expert. Simulation-based teaching reduced patient discomfort and improved candidate skill level. Low-cost model training did not have a negative effect when compared with high-cost model training. Simulated flexible nasolaryngoscopy training may be more accessible with the use of an effective low-cost model.


Horseradish peroxidase study of the localization of motoneurons in the accessory nucleus (XI) of the Japanese toad.
It has been conventionally accepted that the anuran accessory nerve (nXI) only innervates the musculus cucullaris (C). However, we have found that the nXI of the Japanese toad innervated the musculus interscapularis (IS) in addition to the C. The motoneurons innervating these muscles were labelled by the intramuscular injection of horseradish peroxidase (HRP). In the accessory nucleus (XI), the motoneurons were somatotopically organized: the C motoneurons were localized more rostrally, while the IS motoneurons more caudally.


Relationship between obesity-related anthropometric indicators and cognitive function in Chinese suburb-dwelling older adults.
Studies relating obesity to cognition in older people show conflicting results, which may be explained by the choice of obesity indicators. This study aimed to investigate the relationship between obesity-related indicators and cognitive impairment, especially between different age or gender subgroups, and explore whether obesity-related indicators were related to specific cognitive domains. This was a cross-sectional study on 1753 participants aged ≥ 60 years (41.0% men; aged 71.36 ± 5.96 years). Obesity-related indicators included body mass index (BMI), waist circumference (WC), calf circumference (CC), waist to hip ratio (WHR), waist to calf circumstance ratio (WCR), fat to fat-free mass ratio (FM/FFM). The Mini-Mental State Examination scale (MMSE) was used to assess cognitive function. Cognitive impairment was defined as a score ≤ 17 for illiterates, ≤ 20 for participants with primary school education, and ≤ 24 for those with junior high school degrees or above. Multiple logistic regression analysis was used to estimate multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs). Restricted cubic splines were used to analyze and visualize the linear relationships. The prevalence of cognitive impairment was 18.77%. In the fully adjusted model, CC was negatively associated with cognitive impairment (OR = 0.94, 95% CI: 0.90-0.98). Further analysis showed that CC correlated positively with recall and place orientation. A higher FM/FFM was found to be associated with a higher prevalence of cognitive impairment (OR: 1.44, 95%CI: 0.88-2.35, P for trend = 0.029); this association was notable in women (P for trend = 0.002) and the oldest (P for trend = 0.009), and so did the potential effect of BMI on cognitive impairment (70-80 years: P for trend = 0.011; ≥ 80 years: P for trend = 0.013). No statistically significant association was found between cognitive impairment and WC, WHR, or WCR. CC and FM/FFM were associated with cognitive impairment in older people. Future research needs to distinguish the effects of fat and muscle mass on cognitive function, with special attention to different ages and genders.


Mobilization of Hematopoietic Progenitor Cells for Autologous Transplantation Using Pegfilgrastim and Plerixafor: Efficacy and Cost Implications.
Filgrastim (FIL) is the most common growth factor combined with plerixafor for autologous hematopoietic progenitor cell mobilization, but requires daily, multi-injection administration. We adopted a standardized mobilization regimen with pegfilgrastim (PEG) and upfront plerixafor, allowing for a single injection given the long half-life and slow elimination of PEG. Between 2015 and 2017, a total of 235 patients with lymphoma or plasma cell dyscrasias underwent mobilization with PEG 6 mg on day 1 and upfront plerixafor 24 mg on day 3, followed by apheresis on day 4 regardless of peripheral blood CD34+ cells. The median CD34+ cells/mm3 in peripheral blood on first day of collection was 48 and median collection yield was 7.27 × 106 CD34+ cells/kg (range, 0.32 to 39.6 × 106 CD34+ cells/kg) after a mean of 1.6 apheresis collections. Overall, 83% of patients achieved the mobilization target, and 95% reached the minimum necessary CD34+ cell yield to proceed with transplantation (2 × 106 CD34+ cells/kg). Because FIL is weight-based and dosed daily, the cost comparison with PEG is influenced by patient weight and number of apheresis sessions required. A cost simulation using actual patient data indicates that PEG is associated with lower cost than FIL for the majority of patients. Autologous hematopoietic progenitor cell mobilization with PEG and plerixafor is practical, effective, and not associated with increased cost compared with FIL mobilization.


The Sleep Disturbance Numerical Rating Scale: Content Validity, Psychometric Validation, and Meaningful Within-Patient Change in Prurigo Nodularis.
Sleep is often disturbed in patients with prurigo nodularis (PN). To address the lack of validated patient-reported outcome (PRO) measures for quantifying sleep disturbance in PN, we evaluated the Sleep Disturbance Numerical Rating Scale (SD NRS) as a single-item PRO measure for quantifying sleep disturbance in PN. Adults with PN participated in qualitative interviews, which included concept elicitation and cognitive debriefing of the SD NRS. The SD NRS was evaluated psychometrically using data from a phase 2 randomized trial in adults with PN (NCT03181503). Other PRO assessments included the Average Pruritus (AP) NRS, AP Verbal Rating Scale (VRS), peak pruritus (PP) NRS, PP VRS, and Dermatology Life Quality Index (DLQI). Reliability, validity, and responsiveness of the SD NRS were evaluated, and meaningful within-patient change was estimated from qualitative interview responses and quantitative trial data. All interview participants (N = 21) experienced sleep disturbance and most (95%) understood the SD NRS as intended. The SD NRS demonstrated test-retest reliability based on intra-class correlation coefficients for itch-stable participants of 0.87 for the AP VRS and 0.76 for the PP VRS. At baseline, Spearman's rank-order correlation coefficients were moderate to strong (0.3-0.8) between the SD NRS and the AP NRS, AP VRS, PP NRS, PP VRS, and DLQI. Known-groups validity was demonstrated by higher (worse) SD NRS scores in participants with worse scores on the AP NRS, AP VRS, PP VRS, and DLQI. Improvements in SD NRS scores were greater in participants classified as "improved" versus "worsened/unchanged" on the anchor PROs. A 2- to 4-point decrease on the 11-point SD NRS scale was identified as a meaningful within-patient change. The SD NRS is a well-defined, reliable, and valid PRO measure that can be used in daily practice and clinical trials to capture sleep disturbance in adults with PN.


The long-term fate of the gallbladder after endoscopic sphincterotomy. Complete follow-up study of 122 patients.
One hundred twenty-two patients with common bile duct stones and intact gallbladders underwent endoscopic sphincterotomy without cholecystectomy and were followed for 6 months to 9 years (mean 3 years). Nineteen patients died from unrelated causes. One hundred of 103 surviving patients (97 percent) were asymptomatic, whereas 3 had complaints. Acute cholecystitis did not occur in 91 patients without gallstones, whereas it did occur in 5 of 31 patients (16 percent) with gallstones (25 patients) or nonvisualization of the gallbladder (6 patients). Two patients in the former subgroup had formation of new gallstones. We conclude that cholecystectomy should be advocated whenever possible in patients with gallstones or nonvisualization of the gallbladder after endoscopic sphincterotomy due to the high incidence of acute cholecystitis in this subgroup and that operation is not necessary in patients without gallstones; however, one should be aware of possible formation of new stones in the gallbladder.


Medial maxillary (nasomaxillary buttress) fracture: Two case reports.
Medial maxillary fractures are defined as fractures of the medial aspect of the maxilla, that is, fractures of the nasomaxillary buttress. The diagnosis of medial maxillary (nasomaxillary buttress) fractures is challenging because of its similarities with nasal, and naso-orbito-ethmoidal (NOE) fractures. The patients included a 17-year-old Japanese man and a 37-year-old Japanese woman with facial injuries. Swelling of the affected cheek, nasal hemorrhage, periorbital ecchymosis, and C-shaped deviation of the nasal dorsum with normal nasal tip and root position were observed. Mild hypesthesia was noted in the affected region innervated by the left infraorbital nerve. Telecanthus, double vision, eye movement disorder, epiphora, trismus, tooth fracture, and malocclusion were absent in both cases. Based on clinical signs and imaging findings, the patients were diagnosed with medial maxillary (nasomaxillary buttress) fracture. The 17-year-old man underwent a reduction of the medial aspect of the maxillary bone with the treatment of concomitant fractures, and the 37-year-old woman did not request treatment. Medial maxillary (nasomaxillary buttress) fractures are not included in any current classification of the maxillary fracture patterns. As medial maxillary (nasomaxillary buttress) fractures are similar to nasal, and NOE fractures, careful differential diagnosis is required before selecting the surgical procedure to be performed because the treatment of concomitant fractures is also necessary.


Trends in Use of Oral Anticoagulants in Older Adults With Newly Diagnosed Atrial Fibrillation, 2010-2020.
Undertreatment of older adults with atrial fibrillation with anticoagulation therapy is an important practice gap. It has been posited that the availability of direct oral anticoagulants (DOACs) would improve oral anticoagulant (OAC) initiation in older adults with atrial fibrillation given their superior safety profile compared with warfarin. To systematically examine trends in OAC initiation and nonadherence in older adults with atrial fibrillation and coexisting geriatric conditions. This retrospective cohort study uses administrative claims data from Optum's Clinformatics Data Mart from January 1, 2010, to December 31, 2020. Participants included beneficiaries of Medicare Advantage plans aged 65 years and older with atrial fibrillation and elevated risk of ischemic stroke. Data analysis was performed from October 2021 to October 2022. Coexisting dementia, frailty, and anemia. The primary outcomes were OAC initiation within 12 months after the first diagnosis of atrial fibrillation per year and nonadherence with OAC per year (defined as <80% of proportion of days covered among patients newly started on OAC in each year). There were 21 603 to 51 236 patients per year (total for 2010-2020, 381 488 patients) in the OAC-eligible incident AF cohort (mean [SD] age, 77.2 [6.1] to 77.4 [6.8] years; 13 871 [51.8%] to 22 901 [49.8%] women). OAC initiation within 12 months after incident AF increased from 20.2% (5405 of 26 782 patients) in 2010 to 32.9% (7111 of 21 603 patients) in 2020. DOAC uptake increased from 1.1% (291 of 26 782 patients) to 30.9% (6678 of 21 603 patients), and warfarin initiation decreased from 19.1% (5114 of 26 782 patients) to 2.0% (436 of 21 603 patients). Older age (odds ratio [OR], 0.98; 95% CI, 0.98-0.98), dementia (OR, 0.57; 95% CI, 0.55-0.58), frailty (OR, 0.74; 95% CI, 0.72-0.76), and anemia (OR, 0.75; 95% CI, 0.74-0.77) were associated with lower odds of OAC initiation. During the study period, the median (IQR) proportion of days covered increased from 77.6% (41.0%-96.4%) to 90.2% (57.4%-98.6%), and OAC nonadherence decreased from 52.2% (2290 of 4389 patients) to 39.0% (3434 of 8798 patients). Since the introduction of DOACs, OAC initiation in older adults with has improved but remained suboptimal in 2020. Additional strategies are needed to improve stroke prophylaxis in all older adults with atrial fibrillation including those with coexisting dementia, frailty, and anemia.


From mundane medicines to euphorigenic drugs: How pharmaceutical pleasures are initiated, foregrounded, and made durable.
Examining how pharmaceuticals are used to induce pleasure presents a unique opportunity for analyzing not only how pleasure is assembled and experienced through distinct consumption practices but also how mundane medicines can become euphorigenic substances. Drawing on qualitative research on the non-medical use of prescription drugs by young adults in the United States, this paper utilizes Actor-Network Theory (ANT) to examine how prescription medicines come to produce pleasure. Our research found an indeterminacy of experience as individuals were initiated into prescription drug pleasures. We also found that euphorigenic effects coalesce and are foregrounded through subsequent use, and that pleasure and other forms of gratification are made durable through repeated and deliberate pharmaceutical consumption. Understanding how individuals are socialized into pharmaceutical pleasure, and how assemblages act to constitute the euphorigenic potential of pharmaceutical misuse, may allow for more context-appropriate intervention efforts. We suggest that the euphorigenic properties ascribed to prescription drugs are not inherent in their pharmaceutical formulations, but instead emerge through interactions within networks of heterogeneous actants.


Effects of repeated sleep deprivation in the dark- or light-period on sleep in rats.
This study was designed to examine the differences between sleep duration and EEG when sleep was restricted to the rest- or activity-phase for 5 successive days, achieved by repeated sleep deprivation in the dark (DSD) or light-period (LSD). In the DSD-experiment the percentages of the vigilance states were comparable to the level of the baseline light period. In LSD, the amounts of all sleep states increased substantially relative to baseline dark. The sleep episodes were lengthened in DSD and LSD. The duration of NREM-sleep and the sleep episodes remained longer in the light than in the dark, indicating circadian influences. In the first hours after sleep deprivation the delta activity during NREM-sleep was enhanced in LSD and to a lesser extent in DSD. This effect diminished over the consecutive days in both experiments. The EEG energy gained during sleep and its accumulation pattern on each day in DSD and LSD were strikingly similar, thereby reflecting a homeostatic process. After the sleep deprivation days, small changes were observed in the distribution of the vigilance states, the delta activity and EEG energy over the light- and dark-period.


Effects of cAMP and forskolin on caffeine-induced contractures and myofilament Ca-sensitivity in saponin-treated rat ventricular trabeculae.
Trabeculae from the right ventricle of rat were chemically 'skinned' with saponin (50 micrograms ml-1 for 30 min). Caffeine (10 mM) induced a transient contracture as a consequence of Ca(2+)-release from the sarcoplasmic reticulum and subsequent activation of the myofilaments. The amplitude of the caffeine contracture was used as an index of the Ca(2+)-content of the sarcoplasmic reticulum. cAMP (0.1-10 microM) markedly potentiated the caffeine-induced response under standardized conditions. This was interpreted as a cAMP-induced increase in Ca2+ accumulation by the sarcoplasmic reticulum during the Ca2+ loading period before the application of caffeine. After removal of cAMP, the amplitude of the regularly evoked contractures slowly declined towards standard levels. The characteristic effects of cAMP on the caffeine contracture were mimicked by addition of forskolin (10(-6) M), a substance known to stimulate cAMP production by adenylate cyclase. The results suggest that a significant quantity of functional adenylate cyclase persists after saponin treatment. In these preparations cAMP had no effect on the apparent Ca(2+)-sensitivity of the myofilaments. If the preparations were exposed briefly to saponin, cAMP caused a decrease in the apparent Ca2+ sensitivity of the contractile proteins. However, further exposure to saponin, or to Triton X-100, caused a marked increase in maximum Ca(2+)-activated force (Cmax). It was concluded that 'briefly' saponin-treated preparations, exhibiting a reduction in Ca2+ sensitivity in response to cAMP, are not uniformly permeable to the bathing solution.


Ammonia emissions from different pig production scales and their temporal variations in the North China Plain.
Pig production systems in China are shifting from small to industrial scale. Significant variation in housing ammonia (NH3) emissions can exist due to differences in diet, housing design, and management practices. However, there is a knowledge gap regarding the impacts of farm-scale in China, which may be critical in identifying hotspots and mitigation targets. Here, continuous in-situ NH3 concentration measurements were made at pig farms of different scales for sows and fattening pigs over periods of 3-6 days during two different seasons (summer vs. winter). For the sow farms, NH3 emission rates were greater at the small farm (summer: 0.52 g pig-1 hr-1; winter: 0.21 g pig-1 hr-1) than at the large farm (summer: 0.34 g pig-1 hr-1; winter: 0.12 g pig-1 hr-1). For the fattening pig farms, NH3 emission rates were greater at the large farm (summer: 0.22 g pig-1 hr-1; winter: 0.16 g pig-1 hr-1) than at the small farm (summer: 0.19 g pig-1 hr-1; winter: 0.07 g pig-1 hr-1). Regardless of farm scale, the NH3 emission rates measured in summer were greater than those in winter; the NH3 emission rates were greater in the daytime than at the nighttime; a positive relationship (R2 = 0.06-0.68) was established between temperature and NH3 emission rate, whereas a negative relationship (R2 = 0.10-0.47) was found between relative humidity and NH3 emission rate. The effect of farm-scale on indoor NH3 concentration could mostly be explained by the differences in ventilation rates between farms. The diurnal variation in NH3 concentration could be partly explained by ventilation rate (R2 = 0.48-0.78) in the small traditional farms and by emission rate (R2 = 0.26-0.85) in the large industrial farms, except for the large fattening pig farm in summer. Overall, mitigation of NH3 emissions from sow farms should be a top priority in the North China Plain. Implications: The present study firstly examined the farm-scale effect of ammonia emissions in the North China Plain. Of all farms, the sow farm was identified as the greatest source of ammonia emission. Regardless of farm scale, ammonia emission rates were observed to be higher in summer. Ammonia concentrations were mostly higher in the large industrial farms partly due to lower ventilation rates than in the small traditional farms.


Survey of the citrus leprosis vector (Brevipalpus yothersi) and phytoseiids in spontaneous plants of an organic citrus orchard.
Citrus leprosis (CL) is one of the most important viral diseases in sweet orange orchards in Latin America. It is caused by members of at least five species of the so-called Brevipalpus-transmitted viruses (BTV), and the prevalent is Citrus leprosis virus C (CiLV-C). This virus has the broadest host range amongst all CL-associated viruses and is transmitted by Brevipalpus yothersi, a polyphagous mite that can colonize a large variety of host plants, including some spontaneous ground cover plants. But if, on one hand, spontaneous plants can host CL virus and vector, on the other hand, they can offer alternative food for predators, equally common in organic citrus orchards. Brevipalpus yothersi and predator mites were surveyed in 33 spontaneous plants of a Westin sweet orange orchard conducted under organic production system in Brazil, from June 2010 to April 2011. Predatory mites were identified as phytoseiids, and Iphiseiodes zuluagai was the prevalent species, representing 58% of all predators. Other phytoseiids were considered accidental species in the area. Ageratum conyzoides and Alternanthera tenella were the most represented plant host species to predators, comprising 28 and 10% of the total surveyed plants, respectively. Brevipalpus yothersi specimens were detected on various spontaneous species: A. conyzoides, A. tenella, Amaranthus deflexus, Bidens pilosa, Ipomoea quamoclit, I. cairica, Merremia cissoides, Solanum americanum, Panicum maximum, and, predominantly, Commelina benghalensis. The latter has been previously reported as host of CiLV-C as well and, therefore, it is recommended to eliminate this species from citrus orchards.


[Characteristics of the estrogen receptor system of the guinea pig uterus].
Physico-chemical parameters of estradiol-receptor interaction in guinea pig uterine cytosol (velocity constants of association and dissociation, half-life time of estradiol-receptor complex, and the value of free energy change) were studied. The number of receptor sites per cell was calculated. It was shown that under conditions of different degree of approximation to the equilibrium, the affinity percentage in the system under study remained unchanged for the majority of steroids, this pointing to the achievement of equilibrium in these cases. The steroid affinity to the analyzed R-system depended on presence of intact 3- and 17beta-hydroxils with somewhat greater significance of 3-(phenolic) hydroxil of steroid molecule.


Septohippocampal and commissural pathways antagonistically control inhibitory interneurons in the dentate gyrus.
Available evidence suggests that a portion of the septohippocampal pathway may form inhibitory synapses on inhibitory interneurons in the dentate gyrus. In contrast, a portion of the commissural input from the contralateral hilus may form excitatory synapses on inhibitory interneurons. To ascertain whether these pathways synapse onto a common population of interneurons, a series of pulses were applied and their effects on perforant path evoked, granule cell population spikes were measured. The population spike was markedly reduced when the perforant path pulse was preceded by a pulse to the contralateral hilus. This inhibition was markedly reduced, however, when a medial septal pulse was applied either prior to, or within 3 ms after the commissural pulse. The disinhibition was critically dependent on the temporal relationship between the medial septal and commissural pulse, and not on the medial septal-perforant path relationship. This finding suggests that the septohippocampal pathway inhibits the interneurons through which the commissural pathway is able to inhibit granule cells.


Determining the epidemiologic, outcome, and prognostic factors of oral malignant melanoma by using the Surveillance, Epidemiology, and End Results database.
The authors conducted a retrospective analysis to determine the epidemiologic, outcome, and prognostic factors in patients with oral malignant melanoma (OMM). The authors used the US National Cancer Institute's Surveillance, Epidemiology, and End Results database to analyze patients with OMM from 1973 to 2012. Study variables included age, sex, race, decade of diagnosis, extent of disease, tumor size, treatment modality, and socioeconomic status (SES). The search identified 232 patients with OMM. Overall survival (OS) and disease-specific survival (DSS) were 25% and 40%, respectively, at 5 years. Age (OS, P = .004; DSS, P = .294), surgical resection (OS, P = .046; DSS, P = .005), and extent of disease (OS, P < .001; DSS, P < .001) were independent survival determinants; tumor size was an independent predictor of OS (P = .085). For confined and locally invasive disease, surgery (OS, P = .001; DSS, P = .004) and size (OS, P = .154; DSS, P = .007) were independent determinants of OS and DSS. For metastatic disease, surgery (OS, P = .675; DSS, P = .518) was a survival determinant for both OS and DSS, whereas radiotherapy predicted improved OS (hazard ratio, 0.18; 95% confidence interval, 0.03 to 0.99; P = .049). Age at diagnosis, decade of diagnosis, extent of disease, tumor size, and SES are prognostic factors related to OMM survival. Surgical resection and radiation therapy both improve OMM survival. Early and detailed examinations for OMM are critical to improving the survival rate in patients with OMM, especially in older patients and patients of lower SES.


Population structure of the intertidal copepod Tigriopus californicus as revealed by field manipulation of allele frequencies.
Allele frequencies in natural T. californicus populations were perturbed by introduction of copepods from neighboring differentiated populations. In five experiments, the Gpt F allele was introduced into single recipient pools at a frequency of approximately 20%. In each case, the introduced allele declined to low frequencies (<3%) in less than one month, apparently due to dilution by residents of other pools on the same outcrop. In a larger scale experiment, the Pgi F was introduced into four pools on a single small rock outcrop; all pools on the outcrop were subsequently monitored. While the allele frequency fell from approximately 40% to 10% during the first six weeks after the transplant, no further change in frequency was observed for the duration of the experiment (16 months). Within six weeks some spread of the allele to non-recipient pools on the same outcrop was observed; by eight months, allele frequencies in all pools on the outcrop were similar. Hence, despite the extensive turnover of subpopulations as single pools evaporate or are washed out, genetic homogeneity and stability of entire outcrops are maintained via extensive inter-pool gene flow; this contrasts sharply with the highly restricted levels of inter-outcrop gene flow.


Investigating Transitional Care to Decrease Post-pancreatectomy 30-Day Hospital Readmissions for Dehydration or Failure to Thrive.
Current literature emphasizes post-operative complications as a leading cause of post-pancreatectomy readmissions. Transitional care factors associated with potentially preventable conditions such as dehydration and failure to thrive (FTT) may play a significant role in readmission after pancreatectomy and have not been studied. Thirty-one post-pancreatectomy patients, who were readmitted for dehydration or FTT between 2009 and 2014, were compared to 141 nonreadmitted patients. Medical record review and a questionnaire-based survey, specifically designed to assess transitional care, were used to identify predictors of readmissions for dehydration or FTT. Logistic regression models were used to evaluate outcomes. On multivariable analysis, the strongest predictors of readmission for dehydration and FTT were the patient's lower educational level (P = 0.0233), the absence of family during the delivery of discharge instructions (P = 0.0098), episodic intermittent nausea at discharge (P = 0.0019), uncertainty about quantity, quality, or frequency of fluid intake (P = 0.0137), and the inability or failure to adhere to the clinician's instructions in the outpatient setting (P = 0.0048). Transitional-care-related factors are found to be associated with post-pancreatectomy readmission for dehydration and FTT. Using these results to identify high-risk patients and implement focused preventive measures combining efficient communication and optimal inpatient and outpatient management could potentially decrease readmission rates.


The Protective and Therapeutic Effect of Exclusive and Combined Treatment with Alpha-ketoglutarate Sodium Salt and Ipriflavone on Bone Loss in Orchidectomized Rats.
This study investigated the effect of alpha-ketoglutarate sodium salt (AKG) and ipriflavone (IP) treatment on the mineralization of the tibia in male rats during the development and after the establishment of osteopenia. One hundred and twenty eight male rats were randomly selected and submitted to either sham-operation (SHO) or orchidectomy (ORX), after which each group were then randomly divided between the two experiments. In Experiment-1, treatment with AKG or/and IP started after a 7-day recovery period, whereas in Experiment-2, the experimental protocol proceeded after a 60-day period of osteopenia establishment. AKG was then administered as an experimental drinking, at a concentration of 1.0 mol/l. As a control, a placebo solution was administered. IP at 50 mg/kg b.w., and physiological saline - PhS (as a control for IP) were applied daily via gavage. After 60 days of experimental treatment, in both experiments, the rats were sacrificed, their body weight recorded, while blood serum (Osteocalcin, CTX) and isolated tibia (weight, length, pQCT, DXA, 3-point bending test) were stored for further analysis. Our results show that during the development of osteopenia, AKG and IP when applied exclusively, counteracts osteopenia development, whereas their usage after the establishment of osteopenia, significantly limits the development of bone disorders. Furthermore, combined treatment of AKG and IP exceeded the effects of their sole usage. In addition, during the development of osteopenia, AKG and IP not only inhibited bone resorption, but markedly stimulated the formation of bone tissue. Finally, after the development of osteopenia, combined treatment with AKG and IP protected the bone tissue against orchidectomy-induced bone loss.


Novel method of intraoperative ocular movement monitoring using a piezoelectric device: experimental study of ocular motor nerve activating piezoelectric potentials (OMNAPP) and clinical application for skull base surgeries.
Intraoperative monitoring systems that utilize various evoked potentials for the detection and/or preservation of cranial nerves have become increasingly common due to recent technical and commercial developments, particularly during skull base surgeries. We established a novel system for the intraoperative monitoring of the extraocular motor nerves (eOMNs) using a piezoelectric device capable of detecting imperceptible vibrations induced by ocular movement, with sensors placed on the eyelids alone. We first evaluated the efficacy and reliability of this device for the intraoperative monitoring of eOMNs in two Beagle dogs. Based on the results, we then determined the appropriate stimulation parameters for use in human surgical cases involving removal of various skull base tumors. Animal experiments revealed that a 0.4 mA monopolar electrical stimulation was required to elicit significant responses and that these responses were not inferior to those obtained via the electrooculogram/electromyogram. Significant responses were also detected in preliminary clinical investigations in human patients, following both direct and indirect monopolar electrical stimulation of the oculomotor and abducens nerves, although obtaining responses from the trochlear nerve was difficult. Intraoperative monitoring using a piezoelectric device provides a simple and reliable method for detecting eOMNs, especially the oculomotor and abducens nerves. This monitoring system can be adapted to various surgeries for skull base tumor.


Retinotectal projection in goldfish to an inappropriate region with a reversal in polarity.
An abnormal, ipsilateral projection was formed by deflecting optic fibers that normally innervate the posterior part of one tectum into the anterior end of the opposite tectum. When anterior recipient tectum was simultaneously denervate, the deflected fibers formed a retinotopic map in this region that was reversed with respect to the anterior-posterior tectal axis.


Heterogeneity in EC50 and nH of GABAA receptors on dorsal root ganglion neurons freshly isolated from adult rats.
GABA activates a Cl- current through the GABAA receptor/ionophore complex that influences excitability of neurons. Studies using expression of cloned cDNAs coding for different GABAA receptor/ionophore subunits suggest that the EC50 and Hill coefficient for GABA are influenced by subunit composition. However, no direct evidence for such heterogeneity has been reported for vertebrate neurons. I have investigated the heterogeneity of EC50 and Hill coefficients (nH) of isolated dorsal root ganglion neurons using the whole-cell patch clamp technique. The EC50 for GABA varied from 26 to 107 microM among neurons. nH calculated from the logistic equation varied from 1.18 to 2.0. A negative correlation was found between the EC50 and nH (r = -0.81). Both nH and EC50 differed between some cells. However, in some instances, nH differed between cells while EC50 values were similar, and in other cells, EC50 values differed and nH was similar. In addition, when cells were categorized according to action potential shape, the EC50 and Hill coefficients differed among cell types in some instances and were similar in other instances. These findings demonstrate that different pharmacological profiles for GABA can be observed in adult mammalian neurons. Selective distribution of such pharmacological subtypes of GABAA receptors may contribute to control of neuronal excitability.


Diet quality and prodromal Parkinson's disease probability in isolated REM sleep behavior disorder.
It is reported that a diet that lowers oxidative stress reduces the prodromal Parkinson's disease (pPD) probability as well as the risk of Parkinson's disease (PD). In this study, we evaluated whether the diet quality of patients with isolated rapid eye movement (REM) sleep behavior disorder (iRBD) were associated with the pPD probability score, PD risk markers, or prodromal markers. Polysomnography (PSG)-confirmed iRBD patients from the Neurology Department at Seoul National University Hospital were enrolled. We calculated the pPD probability using the "Web-based Medical Calculator for Prodromal Risk in Parkinsonism" Diet quality was assessed using the Recommended Food Score (RFS). We enrolled 101 patients with iRBD. The mean RFS score of patients with iRBD was 28.23 ± 9.29, which did not differ from the general population. Among patients with iRBD, the probability of pPD did not differ between the high and low RFS groups. In patients aged <70 years, although total RFS was not correlated with pPD probability (p = 0.529, Spearman rank correlation), legume consumption was negatively correlated with pPD probability (p = 0.032): furthermore, legume consumption was significantly higher in patients with fewer prodromal markers (p = 0.016). Diet quality assessed by RFS did not differ between the general population and patients with iRBD in Korea. Further studies are needed to confirm these protective effects of legume consumption on iRBD, which may have strong implications for the prevention and management of PD.


Bio-psycho-social health assessment in prehospital emergency technicians: A systematic review.
Health is a complex structure and has physical, psychological, and social approaches. The importance and impact of health assessment have caused considerable attention to be paid to the employees of the health system and the determining factors of this relationship. Hence, the main purpose of this study was to find out the bio-psycho-social health situation in prehospital emergency technicians as the research question staff. The present study is a systematic review and data have retrieved through extensive search in Scopus, Web of Science, PubMed (including Medline), Cochrane Library, Irandoc, Magiran, MedLib, and SID databases with a combination of keywords of "Health, " "Assessment, " "Social," "Psychological," "Biological," "Emergency," and "prehospital," according to the search strategy, between 2000 and 202111 studies were reviewed; then, they were entered based on the objectives of the study and narrative analysis was performed by the researcher. After analyzing the articles, a total of 4 factors affecting bio-psycho-social health in prehospital emergency technicians have been extracted and identified, which included health management, bio-psycho-social factors, occupational factors, and behavioral factors. This research showed four factors, namely health management, bio-psycho-social factors, occupational factors, and behavioral factors which could be effective in Bio-Psycho-Social health. Since prehospital emergency services have an important role in maintaining the health of the community, which requires attention to the bio-psycho-social health of emergency personnel, more studies have focused on health management among the four mentioned factors, but the need to examine the other three factors for a more accurate assessment of the health of emergency personnel seems necessary. Therefore, prevention and response strategies based on bio-psycho-social health assessment models are proposed to promote the health of prehospital emergency technician staff.


Cleidocranial dysplasia with hypermobile Ehlers-Danlos syndrome: A case report.
Cleidocranial dysplasia (CCD) is a rare genetic skeletal syndrome. The most common features are open fontanelles, hypertelorism, mid-face retrusion, hypoplasia, or aplasia of the clavicles leading to excessive shoulder mobility, dental abnormalities such as supernumerary, and impacted teeth. This case report describes a 31-year-old male with CCD with several unusual symptoms like generalized joint hypermobility, skin laxity, and smooth skin, which leads to set a diagnosis of hypermobile Ehlers-Danlos syndrome (hEDS). To our knowledge, this is the first case report in the literature that describes a patient with these 2 distinct syndromes CCD and hEDS.


Prostaglandin E2 (PGE2) inhibits an IUD-induced premature luteolysis in sheep.
Fifteen ewes were assigned as they came into estrus to one of three randomized treatment groups: 1. Sham IUD + Vehicle, 2. IUD + Vehicle, and 3. IUD + PGE2 in Vehicle. An IUD was inserted adjacent to the luteal-bearing ovary of unilaterally ovariectomized ewes on day 3 postestrus. Vehicle (Na2CO3) or PGE2 (500 micrograms) in vehicle was given every 4 hours intrauterine through an indwelling uterine cannula from day 3 postestrus until ewes returned to estrus. Luteolysis was advanced in both the Sham IUD and IUD groups receiving vehicle. An IUD-induced premature luteolysis was prevented by PGE based on daily concentrations of progesterone in peripheral blood and the extended interestrous interval. It is concluded that chronic intrauterine injections of PGE2 (500 micrograms) every four hours can prevent an IUD-induced premature luteolysis. It is also concluded that an IUD-induced premature luteolysis is not necessarily through uterine distention.


Comparison of two- and three-dimensional display for performance of laparoscopic total gastrectomy for gastric cancer.
Introduction of three-dimensional (3D) display might remove technical obstacles of laparoscopic surgery and improve laparoscopic skills. We analyzed the effect of 3D technology on operative performance during laparoscopic total gastrectomy (LTG) for gastric cancer and assessed its advantages over two-dimensional (2D) laparoscopy. This study included 30 consecutive surgeries of LTG with esophagojejunostomy by the overlap method performed (3D group, n = 15, 2D group, n = 15). The surgical outcomes were compared between the 3D and 2D groups. Further, we compared the performance time, the frequency of bleeding requiring hemostasis, and the frequency of remaking the surgical view by the assistant's forceps in each laparoscopic scene between the 3D and 2D groups. All surgeries were completed without any complications. The total time of pure laparoscopic scenes was shorter in the 3D than 2D group (154.2 vs. 182.7 min, P = 0.026), and total blood loss was almost the same (10 vs. 20 g, P = 0.195). The operative time during lymphadenectomy in scenes 6 and 7 were significantly shorter in the 3D than the 2D group (scene 6, 13.5 vs. 17.5 min, P = 0.003, and scene 7, 12.4 vs. 18.4, P = 0.025) and esophagojejunostomy (30.3 vs. 39.4 min, P = 0.008). The frequency of tissue exposure by the assistant was significantly less in the 3D group than the 2D group in scenes 6 and 7 (scene 6, n = 3.0 vs. 4.0, P = 0.006, and scene 7, n = 3.0 vs. 4.0, P = 0.017). 3D display is useful due to improvement of surgical skill during difficult situations such as lymphadenectomy around the celiac artery, which requires handling in the tangential view, and reconstruction using the suturing technique in a narrow space.


Limited impact of the COVID-19 pandemic on colorectal cancer care in the Netherlands in 2020.
The COVID-19 pandemic had a major impact on the health services worldwide. We aimed to investigate the impact of the pandemic on colorectal cancer (CRC) care in the Netherlands in 2020. CRC patients, diagnosed in 2018-2020 in the Netherlands, were selected from the Netherlands Cancer Registry (NCR). The year 2020 was divided in four periods reflecting COVID-19 developments in the Netherlands (pre-COVID, 1st peak, recovery period, 2nd peak) and compared with the same periods in 2018/2019. Patient characteristics and treatment were compared using the Chi-squared test. Median time between diagnosis and treatment, and between (neo)adjuvant therapy and surgery were analyzed by the Mann-Whitney U test. In total, 38,021 CRC patients were diagnosed in 2018/2019 (n = 26,816) and 2020 (n = 11,205). Median time between diagnosis and initial treatment decreased on average 4 days and median time between neoadjuvant radiotherapy and surgery in clinical stage II or III rectal cancer patients increased on average 34 days during the three COVID-19 periods compared to the same periods of 2018/2019. The proportion of colon cancer patients that underwent elective surgery significantly decreased with 3.0% during the 1st peak. No differences were found in the proportion of patients who received (neo)adjuvant therapy, systemic therapy, or no anti-cancer treatment. Only minor changes in the care for CRC patients occurred during the COVID-19 pandemic, mostly during the 1st peak. In conclusion, the impact on CRC care in the Netherlands was found to be limited. However, long-term effects cannot be precluded.


Pholcodine, perioperative anaphylaxis, and the European Medicines Agency: finally the decision to remove pholcodine from the market in the European Union.
Two recent case-control studies, both published in the British Journal of Anaesthesia, have shown that intake of pholcodine-containing cough medicines during the year preceding general anaesthesia significantly increased the risk of anaphylaxis caused by neuromuscular blocking agents. Both a French multicentre study and a single-centre study from Western Australia offer strong support to the pholcodine hypothesis for IgE-sensitisation to neuromuscular blocking agents. The European Medicines Agency, criticised for not taking preventive action at its first assessment of pholcodine in 2011, finally recommended a stop to sales of all pholcodine-containing medicines throughout the EU on December 1, 2022. Time will tell whether this reduces the incidence of perioperative anaphylaxis in the EU, as in Scandinavia.


25-hydroxyvitamin D and calcium levels in maternal, cord and infant serum in relation to maternal vitamin D intake.
The plasma levels of 25-hydroxyvitamin D (25-OHD), total calcium, phosphorus and proteins were measured in 40 healthy mothers and their infants at the time of delivery during the months of December and January. Calcium, phosphorus and proteins were again measured in the plasma of the infants on the fourth day of life. Vitamin D intake of the mothers during their last 3 months of pregnancy were estimated by interviews. The mean (+/-SE) plasma levels of 25-OHD was 9.0 +/- 0.9 ng/ml in the mothers and 5.05 +/- 0.4 ng/ml in cords. There was a significant correlation between mother and cord plasma levels (r = 0.75, p less than or equal to 0.001). The concentration gradient of 25-OHD plasma levels between mother and cord is higher at high 25-OHD maternal concentrations. This suggests that the placenta plays a regulating role in the 25-OHD transfer between mother and foetus. The 4-day-old infants from mothers having a suboptimal vitamin D intake (less than 150 IU/day) have a lower mean serum plasma level than infants born from mothers with a vitamin D intake of more than 500 IU/day.


Gender differences in performance for young adults in cognitive tasks under emotional conflict.
Previous studies have shown that men and women behave differently on diverse cognitive tasks. However, gender differences in recognizing and memorizing faces when in emotional conflict situations are unknown. Therefore, a face-word Stroop task (emotional conflict) and subsequent memory task were used in the present study to examine gender differences among young adults in an emotional conflict situation. Behavioural data showed that men were better able to recognize faces while in emotional conflict, whereas women performed better at the memorization task. Emotional conflict had different effects on memorization performance between men and women. Women memorized more incongruent faces and men more congruent ones. The results confirm the need for further neural study in this area.


Biogenesis of the cytochrome bc1 complex of yeast mitochondria. A precursor form of the cytoplasmically made subunit V.
The cytoplasmically made subunit V of the yeast mitochondrial cytochrome bc1 complex is synthesized as a larger polypeptide in vitro. This was shown by programming a reticulocyte lysate with yeast RNA and immunoprecipitating the labeled translation products with a subunit V-specific antiserum. The larger form of subunit V could also be detected in pulse-labeled spheroplasts; upon a subsequent chase, most of it disappeared. A proteolytic fingerprint of the larger form was closely similar to that of the mature subunit. These data suggest that the cytoplasmically made subunit V is translated as a larger precursor which is cleaved to the mature subunit either during or after its entry into the mitochondria.


Advances in Biomedical Imaging, Bioengineering, and Related Technologies for the Development of Biomarkers of Pancreatic Disease: Summary of a National Institute of Diabetes and Digestive and Kidney Diseases and National Institute of Biomedical Imaging and Bioengineering Workshop.
A workshop sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases and the National Institute of Biomedical Imaging and Bioengineering focused on research gaps and opportunities in the development of new biomarkers of pancreatic disease. The session was held on July 22, 2015, and structured into 6 sessions: 1) Introduction and Overview; 2) Keynote Address; 3) New Approaches to the Diagnosis of Chronic Pancreatitis; 4) Biomarkers of Pain and Inflammation; 5) New Approaches to the Detection of Pancreatic Cancer; and 6) Shed Exosomes, Shed Cells, and Shed Proteins. Recent advances in the fields of pancreatic imaging, functional markers of pancreatic disease, proteomics, molecular and cellular imaging, and detection of circulating cancer cells and exosomes were reviewed. Knowledge gaps and research needs were highlighted. The development of new methods for the noninvasive determination of pancreatic pathology; the use of cellular markers of pancreatic function, inflammation, pain, and malignancy; and the refinement of methods to identify cells and cellular constituents of pancreatic cancer were discussed. The further refinement of sophisticated technical methods and the need for clinical studies to validate these new approaches in large-scale studies of patients at risk for the development of pancreatic disease were repeatedly emphasized.


In search of an efficient strategy to monitor disease status of chronic heart failure outpatients: added value of blood biomarkers to clinical assessment.
Blood biomarkers have the potential to monitor the severity of chronic heart failure (CHF). Studies correlating repeated measurements of blood biomarkers with repeatedly assessed New York Heart Association (NYHA) class over a prolonged follow-up period, and concomitantly investigating their associations with clinical endpoints, have not yet been performed. Between 2011-2013, 263 CHF patients were included. At inclusion and subsequently every 3 months, we measured N‑terminal pro-B-type natriuretic (NT-proBNP), high-sensitivity troponin T (Hs-TnT) and C‑reactive protein (CRP), and assessed NYHA class. The primary endpoint comprised heart failure hospitalisation, cardiovascular mortality, cardiac transplantation or left ventricular assist device implantation. Time-dependent Cox models were used. Mean age was 67 ± 13 years, 72% were men and 27% were in NYHA class III-IV. We obtained 886 repeated measures (median 3 [IQR 2-5] per patient). The primary endpoint was reached in 41 patients during a median follow-up of 1.0 [0.6-1.4] year. Repeatedly measured NT-proBNP and Hs-TnT were significantly associated with repeatedly assessed NYHA class, whereas CRP was not (NT-proBNP: β [95% CI]: 1.56 [1.17-2.06]ln(ng/l) increase per point increase in NYHA class, p = 0.002; HsTNT: β [95% CI]: 1.58 [1.21-2.07]). Serially measured NT-proBNP (HR [95% CI]:2.86 [1.73-4.73]), CRP (1.69 [1.21-2.34]) and NYHA class (2.33 [1.51-3.62]) were positively and independently associated with the primary endpoint, whereas Hs-TnT lost statistical significance after multivariable adjustment. A model containing serially measured NYHA class and NT-proBNP displayed a C-index of 0.84, while serially measured NYHA class and CRP showed a C-index of 0.82. Temporal NT-proBNP, CRP and NYHA class patterns are independently associated with adverse clinical outcome. Serially measured NT-proBNP and NYHA class are best suited for monitoring CHF outpatients.


The pharmacological effects of buflomedil in patients with multi-cerebral infarcts dementia: an open, preliminary assessment.
The influence of buflomedil on brain circulation was investigated in an open, preliminary trial in 12 patients with dementia caused by multi-cerebral infarcts. Patients were given 150 mg buflomedil 3-times daily for a period of 6 months. Assessments carried out before treatment included regional cerebral blood flow measurements, using a 133Xenon technique, as well as psychometric tests (Weschler and Benton), psychiatric and neurological evaluations, and routine clinical and laboratory (blood and urine) examinations. The tests and investigations were repeated on Days 90 and 180 of treatment. The results showed that mean regional cerebral blood flow increased by 15% to 22% and 16% to 24% in the right and left hemispheres, respectively, by the end of the trial, and marked improvements were noted in psychiatric symptoms and scores in the psychometric tests. A controlled, double-blind study is being planned to validate these preliminary findings.


Altered ganglioside biosynthesis in mouse cell cultures following transformation with chemical carcinogens and x-irradiation.
Chemicaly and x-ray-transformed subclones of BALB/c 3T3 mouse embryo cells were found to have reduced amounts of the mono- and disialogangliosides galactosyl-N-acetylgalactosaminyl-[N-acetylneuraminyl]-galactosylglucosylceramide (Gm1) and N-acetylneuraminylgalactosyl-N-acetylgalactosaminyl-[N-acetylneuraminyl]-galactosylglucosylceramide (Gd1a), and increased amounts of N-acetylgalactosaminyl-[N-acetylneuraminyl]-galactosylglucosylceramide (Gm2). The activity of the enzyme UDP-Gal:Gm2 galactosyltransferase was reduced to between 2.7 and 14.3% of normal in the transformed clones. Other ganglioside glycosyltransferase activities were unaffected. This enzymatic change was consistent with the observed alteration in ganglioside pattern in the transformed cells. The residual galactosyltransferase activity in the transformed cells was kinetically similar to the normal enzyme, suggesting that transformation alters ganglioside biosynthesis by blocking enzyme synthesis at the translational or transcriptional levels.


Unusual motor unit firing behavior in older adults.
Motor unit firing behavior was studied in the first dorsal interosseus (FDI) and tibialis anterior (TA) muscles of 10 aged subjects during slow, isometric contractions. Previous study in younger individuals had shown that motor units are recruited and derecruited in an orderly manner whereby the early-recruited units are the last to be derecruited. However, there were several examples in the old subjects in which some high-threshold motor units were derecruited at much lower levels of force. Concurrent antagonist firing in an effort to maintain the required precision is considered a likely candidate for such prolonged motor unit activation.


Double-blind, randomized, placebo-controlled study of molsidomine in patients with stable effort angina receiving beta-blocker therapy with atenolol.
A randomized, double-blind, placebo-controlled trial was performed in 12 patients with chronic and stable effort angina to study the antianginal and anti-ischemic actions of a single dose of molsidomine in addition to long-term therapy with a long-acting beta-adrenergic blocker (100 mg of atenolol daily). Efficacy was assessed by means of objective endpoints obtained by computer-assisted exercise testing. The mean exercise time to produce angina improved significantly from 330 +/- 38 seconds (mean +/- SEM) in patients after administration of atenolol and placebo to 420 +/- 36 seconds after administration of atenolol and molsidomine. Similar significant improvements were seen in ST segment changes at an identical exercise duration, in maximal heart rate, and in maximal exercise duration. The increased anginal threshold and the reduced ischemic changes were not explained by changes in the rate-pressure product at submaximal levels. Thus molsidomine showed antianginal and anti-ischemic efficacy in the treatment of stable effort angina additional to the effect of long-term therapy with beta-adrenergic blockers.


A Data-Validated Stoichiometric Model for the Priming Effect.
Due to global warming, interest in sequestering carbon by appropriately managing soils has contributed to studying the dynamic exchange of carbon and nitrogen in soils and atmospheric CO[Formula: see text]. The priming effect, or the intensified CO[Formula: see text] emissions from soil organic matter (SOM) decomposition in short periods by using labile substrates, has been a topic of interest over the last decades. A combination of two experimentally supported mechanisms explains the priming effect phenomenon, and for the first time, we combine them in a novel stoichiometric model. The model considers the effects of labile substrate utilization in soils during the SOM decomposition and how CO[Formula: see text] emissions rates are affected. Laboratory data and a local sensitivity analysis validate the accuracy and robustness of the model. We find an optimized ratio of labile carbon and nitrogen that intensifies SOM decomposition for different soil features. The priming effect is weakened as C/N in SOM increases for nutrient-poor soils and is independent of C/N in SOM for nutrient-rich soils. The time required for microorganisms to decompose SOM at its maximum rate is delayed only for labile carbon treatments and poor-nutrient soils but remains constant otherwise. Finally, the SOM degradation efficiency determines the priming effect's acceleration or reduction under different soil treatments.


Integrative epigenomic analyses of small cell lung cancer cells demonstrates the clinical translational relevance of gene body methylation.
DNA methylation is a key regulator of gene expression and a clinical therapeutic predictor. We examined global DNA methylation beyond the generally used promoter areas in human small cell lung cancer (SCLC) and find that gene body methylation is a robust positive predictor of gene expression. Combining promoter and gene body methylation better predicts gene expression than promoter methylation alone including genes involved in the neuroendocrine classification of SCLC and the expression of therapeutically relevant genes including MGMT, SLFN11, and DLL3. Importantly, for super-enhancer (SE) covered genes such as NEUROD1 or MYC, using H3K27ac and NEUROD1, ASCL1, and POU2F3 ChIP-seq data, we show that genic methylation is inversely proportional to expression, thus providing a new approach to identify potential SE regulated genes involved in SCLC pathogenesis. To advance SCLC transitional research, these data are integrated into our web portal (https://discover.nci.nih.gov/SclcCellMinerCDB/) for open and easy access to basic and clinical investigators.


Retinal arterial abnormalities correlate with brain white matter lesions in cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy.
The aim of this study is to determine the relationship between retinal abnormalities and brain white matter hyper-intensities (WMH) in symptomatic patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL). Fifteen patients with CADASIL and fifteen age-matched healthy control individuals were enrolled in this study. Ophthalmological examinations were performed on all subjects and all patients with CADASIL underwent cerebral MRI scanning. Retinal artery abnormalities were graded according to the Keith-Wagener-Barker hypertensive retinopathy classification. WMH were classified as punctuate (Grade 1), nodular or early confluent (Grade 2) and diffusly confluent (Grade 3). Partial correlation was used to assess the relationship between retinal abnormalities and WMH, controlling for age. Retinal arteriole narrowing existed in 15 cases and 2 controls, with Grade 2 and Grade 3 being the most common grading of retinal artery narrowing in patients with CADASIL. All patients had WMH on MRI, rated as Grade 1 in one patient, Grade 2 in five patients and Grade 3 in nine patients. The correlation coefficient of retinal arteriole narrowing and WMH was 0.546 (P < 0.05). Retinal arteriole narrowing may be associated with the severity of the cerebral lesions in CADASIL.


Long-term effects of prophylactic and therapeutic lamivudine treatments in hepatitis B surface antigen-positive renal allograft recipients.
Among hepatitis B surface antigen (HBsAg)-positive renal allograft recipients, post-transplant immunosuppression is associated with the occurrence of hepatocellular carcinoma (HCC) and liver-related complications. Lamivudine has proven beneficial in short-term post-transplant follow-up. Between 2000 and 2009, 26 adult HBsAg-positive renal allograft recipients received lamivudine prophylaxis (Group 1) and another 28 patients received therapeutic lamivudine (Group 2) due to post-transplant hepatitis B reactivation. The historical control group included 43 HBsAg-positive renal allograft recipients who did not receive lamivudine therapy (Group 3). No subjects in Group 1 presented HCC or liver-related complications and the 10-year HCC incidence of Group 2 and Group 3 was 4.2 and 34 %, respectively. Furthermore, the HCC-free survival rates as well as the 10-year patient and graft survival rates of Group 1 and Group 2 were significantly higher than those of Group 3. However, the rates of liver-related complications and graft rejection of Group 2 and Group 3 were both higher than those of Group 1. Additionally, the HBV mutation-free rate of lamivudine was significantly higher in Group 1 than in Group 2. Lamivudine antiviral treatment, either on a prophylactic or therapeutic basis, provided long-term benefits for HBsAg-positive renal allograft recipients, in terms of reducing the occurrence of HCC and prolonging patient and graft survival. Furthermore, compared with therapeutic lamivudine, lamivudine prophylaxis appears to significantly reduce the incidence of liver-related complications, graft rejection, and lamivudine resistance.


Involvement of intracellular glutathione in zinc deficiency-induced activation of hepatic stellate cells.
Hepatic stellate cells (HSC) play an important role in the development of liver cirrhosis. They are a major source of extracellular matrix and during fibrogenesis undergo an activation process characterized by increased proliferation and collagen synthesis. In this study, we investigated the anti-fibrogenic effect of zinc supplementation on zinc deficiency induced HSC activation. Isolated HSC were incubated with or without zinc chelator, diethylenetriamine penta-acetic acid (DTPA). Type I collagen expression in HSC was detected by immunohistochemistry. The involvement of glutathione (GSH) homeostasis in the anti-fibrogenic action of zinc was also investigated, as GSH is implicated in many cellular events, such as regulation of cell proliferation, remodeling of extracellular matrix and oxidative stress. Intracellular GSH was measured by HPLC. Enhanced type I collagen expression, apoptosis and cell cycle arrest were found in HSC when DTPA was added, but they were inhibited with supplementation with zinc. Zinc deficiency caused a reduction in intracellular GSH 8 h after the addition of DTPA compared with control levels. The results of this study show that in HSC, the chelation of zinc triggers a progression of collagen synthesis and this involves the depletion of intracellular GSH levels after the addition of DTPA.


Oestrogen-induced increase in uterine cGMP content: a true hormonal action?
The dependency of the oestrogen-induced increase in uterine cGMP content towards the cytosol-nuclear receptor system was investigated. The following observations were made: (1) With oestradiol-17 beta (E2-17 beta), U11-100A (UA) or CI-628 (CI) the cGMP response elicited in the uterus of immature rats followed a course that was parallel to (yet delayed by about 1 h from it) the known time-course evolution of nuclear occupancy by the complex formed by each compound with the oestrogen-receptor. (2) While a marked (about 2-fold) increase in uterine cGMP content was obtained with 0.1 microgram E2-17 beta, oestradiol-17 alpha (E2-17 alpha) given at the same dose had no effect on uterine cGMP. (3) The 2--3 h response to E2-17 beta (or to UA) could not be obtained in animals that had received a first injection of E2-17 beta, 2 h, or of one of the anti-oestrogens UA or tamoxifen, 20--22 h prior to the test injection of E2-17 beta. Those 3 treatments have in common that, at the time indicated, they create a state of depletion in the uterine cytosolic receptor population. The cGMP response to E2-17 beta was restored 20--22 h following a first injection of E2-17 beta. This time is known, in this case, to correspond to full replenishment of the cytosol-receptor population. In all those tests, the wet weight increase, measured in the same organs, behaves exactly as did the cGMP response. These results support the conclusion that the increase in uterine cGMP after oestrogen administration to the immature rat, represents a true hormonal action which, like other uterotrophic actions of oestrogens, involves binding of the hormone by the cytosol receptor.


The future of Alpine Run-of-River hydropower production: Climate change, environmental flow requirements, and technical production potential.
Past studies on the impacts of climate change (CC) on Alpine hydropower production have focused on high-head accumulation power plants. We provide one of the first comprehensive, simulation-based studies on CC impacts on Alpine Run-of-River (RoR) production, also considering effects of environmental flow requirements and technical increase potential. We simulate future electricity production under three emissions scenarios for 21 Swiss RoR plants with a total production of 5.9 TWh a-1. The simulations show an increase in winter production (4 % to 9 %) and a decrease in summer production (-2 % to -22 %), which together lead to an annual decrease of about -2 % to -7 % by the end of the century. The production loss due to environmental flow requirements is estimated at 3.5 % of the annual production; the largest low-elevation RoR power plants show little loss, while small and medium-sized power plants are most affected. The potential for increasing production by optimising the design discharge amounts to 8 % of the annual production. The largest increase potential is related to small and medium-sized power plants at high elevations. The key results are: i) there is no linear relationship between CC impacts on streamflow and on RoR production; the impacts depend on the usable streamflow volume, which is influenced by the Flow Duration Curve, environmental flow requirements, and design discharge; ii), the simulated production impacts show a strong correlation (>0.68) with the mean catchment elevation. The plants at the highest elevations even show an increase in annual production of 3 % to 23 %, due to larger shares of precipitation falling as rain instead of snow. These general results are transferable to RoR production in similar settings in other Alpine locations and should be considered in future assessments. Future work could focus on further technical optimisation potential, considering detailed operational data.


Ca2+/calmodulin-activated protein phosphatase (PP2B) of Saccharomyces cerevisiae. PP2B activity is not essential for growth.
Protein phosphatase (PP2B) whose activity is stimulated 12-20-fold by Ca2+/calmodulin (CaM) was partially purified by CaM-Sepharose and heparin-agarose chromatographies from cell extract of the yeast Saccharomyces cerevisiae. PP2B activity was not detectable in a mutant in which two genes (CMP1 and CMP2) encoding homologs of mammalian PP2B catalytic subunit were disrupted. We have previously shown that the double gene disruption has no significant effect on the growth of yeast [1991, Mol. Gen. Genet. 227, 52-59]. The results indicated that CMP1 and CMP2 are the only genes that encode the PP2B catalytic polypeptide in S. cerevisiae, and PP2B activity is not essential for the growth of the yeast under normal conditions.


Diverticulitis in young versus elderly patients: a meta-analysis.
To compare patients younger and older than 50 years with diverticulitis with regard to complications, disease recurrence and to the need for surgery. A literature review and meta-analysis was conducted according to the PRISMA guidelines. MEDLINE, Embase and the Cochrane databases were searched for longitudinal cohort studies comparing patients younger and older than 50 years with diverticulitis. Eight studies were included with a total of 4.751 (male:female 1:0.66) patients younger and 18.328 (male:female 1:1.67) older than 50 years of age. The risk of developing at least one recurrent episode was significantly higher among patients younger than 50 years (pooled RR 1.73; 95% CI 1.40-2.13) with an estimated cumulative risk of 30% compared with 17.3% in older patients. The risk of requiring surgery during hospitalization for a primary episode of diverticulitis was equal in both age groups (pooled RR 0.99; 95% CI 0.74-1.32) and estimated at approximately 20%. Patients younger than 50 years more frequently required urgent surgery during hospitalization for a subsequent recurrent episode (pooled RR 1.46; 95% CI 1.29-1.66); the cumulative risk was 7.3% in younger and 4.9% in patients older than 50 years. Patients younger than 50 years only differ substantially in risk for recurrent disease from patients older than 50 years of age. Although the relative risk for requiring urgent surgery for recurrent disease was higher in younger patient, one should consider that the absolute risk difference is relatively small (7.3% vs. 4.9%).


The mechanism of charge density wave in Pt-based layered superconductors: SrPt2As2 and LaPt2Si2.
The intriguing coexistence of the charge density wave (CDW) and superconductivity in SrPt2As2 and LaPt2Si2 has been investigated based on the ab initio density functional theory band structure and phonon calculations. We have found that the CDW instabilities for both cases arise from the q-dependent electron-phonon coupling with quasi-nesting feature of the Fermi surface. The band structure obtained by the band-unfolding technique reveals the sizable q-dependent electron-phonon coupling responsible for the CDW instability. The local split distortions of Pt atoms in the [As-Pt-As] layers play an essential role in driving the five-fold supercell CDW instability as well as the phonon softening instability in SrPt2As2. By contrast, the CDW and phonon softening instabilities in LaPt2Si2 occur without split distortions of Pt atoms. The phonon calculations suggest that the CDW and the superconductivity coexist in [X-Pt-X] layers (X = As or Si) for both cases.


Clinical applications of artificial intelligence in liver imaging.
This review outlines the current status and challenges of the clinical applications of artificial intelligence in liver imaging using computed tomography or magnetic resonance imaging based on a topic analysis of PubMed search results using latent Dirichlet allocation. LDA revealed that "segmentation," "hepatocellular carcinoma and radiomics," "metastasis," "fibrosis," and "reconstruction" were current main topic keywords. Automatic liver segmentation technology using deep learning is beginning to assume new clinical significance as part of whole-body composition analysis. It has also been applied to the screening of large populations and the acquisition of training data for machine learning models and has resulted in the development of imaging biomarkers that have a significant impact on important clinical issues, such as the estimation of liver fibrosis, recurrence, and prognosis of malignant tumors. Deep learning reconstruction is expanding as a new technological clinical application of artificial intelligence and has shown results in reducing contrast and radiation doses. However, there is much missing evidence, such as external validation of machine learning models and the evaluation of the diagnostic performance of specific diseases using deep learning reconstruction, suggesting that the clinical application of these technologies is still in development.


Analysis of survival and prognostic factors of pediatric patients with brain tumor.
To estimate survival and evaluate prognostic factors of pediatric patients with central nervous system (CNS) tumors treated in a single center. Retrospective analysis of survival of 103 children with primary brain tumors diagnosed consecutively from January 2000 to December 2006. Cox regression was used for multivariate analysis of factors that affect overall survival to define possible prognostic factors. Median and mean ages were 7.2 and 7.6 years. There was a male predominance (1.22:1). Most patients had medulloblastomas or primitive neuroectodermal tumors (PNET, 38%), or low-grade astrocytomas (18%). The anatomic site of most tumors was the cerebellum (49%) and the brain stem (21%). Five-year survival after diagnosis was 84% for low-grade astrocytomas and 51% for medulloblastomas and PNET. Prognostic factors for overall survival were histopathological type (high-grade astrocytomas and ependymomas; hazard ratio = 3.7 to 3.9), surgery (hazard ratio of 0.5 for completely resected tumors) and radiotherapy (hazard ratio of 0.5 for patients who underwent radiotherapy). Overall survival of pediatric patients with brain tumors in this study was similar to that found in populations of the United States and Europe. The prognostic factors defined for overall survival are also similar to those published in previous studies.