An electrochemically enhanced solid-phase microextraction approach based on molecularly imprinted polypyrrole/multi-walled carbon nanotubes composite coating for selective extraction of fluoroquinolones in aqueous samples.
In this study, an electrochemically enhanced solid-phase microextraction (EE-SPME) approach based on molecularly imprinted polypyrrole/multi-walled carbon nanotubes (MIPPy/MWCNTs) composite coating on Pt wire was developed for selective extraction of fluoroquinolone antibiotics (FQs) in aqueous samples. During the extraction, a direct current potential was applied to the MIPPy/MWCNTs/Pt fiber as working electrode in a standard three-electrode system, FQ ions suffered electrophoretic transfer to the coating surface and then entered into the shape-complimentary cavities by hydrogen-bonding and ion-exchange interactions. After EE-SPME extraction, the fiber was desorbed with desorption solvent for high-performance liquid chromatography (HPLC) analysis. Some parameters influencing EE-SPME extraction such as applied potential, extraction time, solution pH, ionic strength, and desorption solvent were optimized. EE-SPME showed good selectivity and higher extraction efficiency to FQs compared with that of traditional solid-phase microextraction. EE-SPME coupled with HPLC to determine FQs in water samples, the limits of detection (S/N=3) for the selected FQs are 0.5-1.9 μg L(-1). The proposed method was successfully used to the analysis of FQs spiked urine and soil samples, with recoveries of 85.1-94.2% for the urine samples and 89.8-95.5% for the soil samples.


The absorption of trichloroethylene and its metabolites from the urinary bladder of anesthetized dogs.
In order to examine the absorption of trichloroethylene (TRI) and its metabolites from the urinary bladder of dogs, we injected TRI and its metabolites, i.e., chloral hydrate (CH), free trichloroethanol (F-TCE), trichloroacetic acid (TCA) and conjugated trichloroethanol (Conj-TCE), into the urinary bladder of anesthetized dogs, and measured the agents and their respective metabolites in the blood or serum, urine and bile. The percentage of water absorbed from the urinary bladder was 10-20% 2 h after the administration of all substances. The percentage of agents absorbed was 60-70% for the TRI and TCA groups, and 50-60% for the CH, F-TCE and Conj-TCE groups 2 h after administration. The combined urinary and biliary excretion rates of the absorbed materials from the urinary bladder 2 h after administration were 46% for F-TCE, 30% for CH, 6% for Conj-TCE and 0.5-1.0% for TRI and TCA. Urinary re-excretion rates of the total excreted amounts were 65-70% in TRI, CH and F-TCE groups, about 50% in TCA and 99% in Conj-TCE group. It is possible that all of the substances administered, particularly F-TCE, are metabolized to Conj-TCE in the urinary bladder.


The COPG2, DCN, and SDHD genes are biallelically expressed in cattle.
Imprinted genes are preferentially expressed from either the maternally inherited allele or the paternally inherited allele. Most genes known to be imprinted have been identified and studied in the human and the mouse. There is only a small number of reported imprinted genes in cattle, which is probably because of the limited sequence and polymorphism information available for bovine genes. To study the imprinting status of cattle genes and assess their conservation among mammalian species, the expression patterns of COPG2, DCN, and SDHD genes were examined in a total of 128 fetal and adult tissues. Two single nucleotide polymorphisms (SNPs) were identified in COPG2, three SNPs in DCN, and one SNP in SDHD. These polymorphisms were used to distinguish between monoallelic and biallelic expression using a primer extension method and a sequencing-based approach. In all 128 tissues, COPG2, DCN, and SDHD transcripts showed biallelic expression. Other cattle genes examined to date have been found to be imprinted like their known counterparts in human and mouse. This is the first report of genes that are not imprinted in cattle while the corresponding genes in human or mouse are imprinted. Lack of conservation of imprinting among mammals suggests important biological, developmental, and regulatory consequences.


Somatic Mutations and Clonal Hematopoiesis as Drivers of Age-Related Cardiovascular Risk.
Clonal hematopoiesis of indeterminate potential (CHIP) has been identified as a novel cardiovascular risk factor. Here we review the relationship of lifestyle and environmental risk factors predisposing to somatic mutations and CHIP and provide an overview on age-related cardiovascular outcomes. CHIP has been associated with accelerated atherosclerosis and cardiovascular disease in both epidemiological and experimental studies. The most commonly mutated candidate driver genes are DNMT3A, TET2, JAK2, and ASXL1. The underlying mechanisms appear predominantly related to inflammatory pathways. Although age is the dominant risk factor for developing CHIP, emerging evidence suggests that other factors such as smoking, obesity/type 2 diabetes, or an unhealthy diet play a role in the occurrence of somatic mutations. Evidence suggests a strong link between vascular risk factors, somatic hematopoietic mutations, and age-related cardiovascular disease. Further studies on CHIP biology are required to identify targeted interventions for risk reduction in patients with CHIP and inform the utility of screening strategies.


Relationship between carotid chemoreceptor activity and ventilation in the cat.
The steady-state stimulus-response relations between arterial P02 and PCO2 and the mean activity of carotid chemoreceptors (single and multi-fiber) and ventilation were simultaneously recorded in 48 anesthetized cats. The carotid chemoreceptor activity varied linearly with the increase of arterial PCO2, below and above the normal value, at any given level of arterial P02. A decrease in arterial P02 increased the activity of the carotid chemoreceptors and increased its sensitivity to changes in arterial PCO2, showing multiplicative stimulus interaction. The authors also found that the response in ventilation during hypoxia to changes in arterial PCO2 below the normal value was smaller than that to changes above it, unlike the response of carotid chemoreceptors. This arterial PCO2 quasi-threshold for ventilation was, therefore, not due to a corresponding threshold for the activity of the carotid chemoreceptors but to a central mechanism. Above the central PaCO2 threshold, the ventilatory response to changes in PaCO2 and Pa02 resembled that of chemoreceptors but the ventilation dependent on hypoxia was greater than that could be directly accounted for by the activity of peripheral chemorecepors. A multiplicative interaction between the activity of peripheral chemoreceptors and central CO2 excitation appears to play a role in the regulation of ventilation.


[Guided tissue regeneration: ultrastructure of membranes and review of the literature].
Guided tissue regeneration is an innovative new technique designed to encourage healing of the periodontium by blocking out gingival epithelium and connective tissue from the healing wound. The various types of membranes used in guided tissue regeneration are described and a scanning electron microscopic study of the membranes is presented.


Theta oscillations orchestrate medial temporal lobe and neocortex in remembering autobiographical memories.
Remembering autobiographical events can be associated with detailed visual imagery. The medial temporal lobe (MTL), precuneus and prefrontal cortex are held to jointly enable such vivid retrieval, but how these regions are orchestrated remains unclear. An influential prediction from animal physiology is that neural oscillations in theta frequency may be important. In this experiment, participants prospectively collected audio recordings describing personal autobiographical episodes or semantic knowledge over 2 to 7 months. These were replayed as memory retrieval cues while recording brain activity with magnetoencephalography (MEG). We identified a peak of theta power within a left MTL region of interest during both autobiographical and General Semantic retrieval. This MTL region was selectively phase-synchronized with theta oscillations in precuneus and medial prefrontal cortex, and this synchrony was higher during autobiographical as compared to General Semantic knowledge retrieval. Higher synchrony also predicted more detailed visual imagery during retrieval. Thus, theta phase-synchrony orchestrates in humans the MTL with a distributed neocortical memory network when vividly remembering autobiographical experiences.


A physical perspective on cytoplasmic streaming.
Organisms show a remarkable range of sizes, yet the dimensions of a single cell rarely exceed 100 µm. While the physical and biological origins of this constraint remain poorly understood, exceptions to this rule give valuable insights. A well-known counterexample is the aquatic plant Chara, whose cells can exceed 10 cm in length and 1 mm in diameter. Two spiralling bands of molecular motors at the cell periphery drive the cellular fluid up and down at speeds up to 100 µm s(-1), motion that has been hypothesized to mitigate the slowness of metabolite transport on these scales and to aid in homeostasis. This is the most organized instance of a broad class of continuous motions known as 'cytoplasmic streaming', found in a wide range of eukaryotic organisms-algae, plants, amoebae, nematodes and flies-often in unusually large cells. In this overview of the physics of this phenomenon, we examine the interplay between streaming, transport and cell size and discuss the possible role of self-organization phenomena in establishing the observed patterns of streaming.


Study on biodegradation of some A- and B-trichothecenes and ochratoxin A by use of probiotic microorganisms.
In vitro biodegradation experiments were done using some probiotic microorganisms. DifferentSaccharomyces cerevisiae, Lactobacilli andBacilli strains were tested for their ability to degrade Nivalenol (NIV), Deoxynivalenol (DON), Diacetoxyscirpenol (DAS), T2-Toxin and Ochratoxin A (OTA). The concentrations of selected mycotoxins were in the range of natural occurring toxin contaminations (1ppm for NIV and DON, 500ppb for DAS and T-2 and 50ppb for OTA). No alteration of concentrations could be registered for the tested trichothecenes. The best results could be achieved in experiments with OTA by up to 94% detoxification. Influence of toxins on colony forming unit of all tested microorganisms were recorded. Especially T-2 toxin and DAS have a slowing effect on growth of some strains.


The circumventricular organs participate in the immunopathogenesis of experimental autoimmune encephalomyelitis.
During inflammatory conditions of the central nervous system (CNS), such as in multiple sclerosis or in its animal model, experimental autoimmune encephalomyelitis (EAE), immune cells migrate from the blood stream into the CNS parenchyma and into the cerebrospinal fluid (CSF) spaces. The endothelial blood-brain barrier (BBB) has been considered the most obvious entry site for circulating immune cells. Recently, the choroid plexus has been considered as an alternative entry site for circulating lymphocytes into the CSF. The choroid plexus, belongs to the circumventricular organs (CVOs) localized in the walls of the ventricles. Other CVOs, which similar to the choroid plexus lack an endothelial BBB, have not been considered as possible entry sites for immune cells into the CNS parenchyma or the CSF. Here we asked, whether CVOs are involved in the recruitment of inflammatory cells into the brain during EAE. We performed an extensive immunohistological study on the area postrema (AP), the subfornical organ (SFO), the organum vasculosum of the lamina terminalis (OVLT) and the median eminence (ME) in frozen brain sections from healthy SJL mice and mice suffering from EAE. Expression of cell adhesion molecules, the presence of leukocyte subpopulations and the detection of major histocompatibility complex antigen expression was compared. Similar changes were observed for all four CVOs included in this study. During EAE significantly increased numbers of CD45+ leukocytes were detected within the four CVOs investigated, the majority of which stained positive for the macrophage markers F4/80 and Mac-1. The adhesion molecules ICAM-1 and VCAM-1 were upregulated on the fenestrated capillaries within the CVOs. A considerable upregulation of MHC class I throughout the CVOs and positive immunostaining for MHC class II on perivascular cells additionally documented the immune activation of the CVOs during EAE. A significant enrichment of inflammatory infiltrates was observed in close vicinity to the CVOs. Our data indicate that the CVOs are a site for the entry of immune cells into the CNS and CSF and consequently are involved in the inflammatory process in the CNS during EAE.


Bilateral differences of normal hand strength.
The normal grip strength, pinch strength and key strength was determined by specially designed dynamometers in 30 females and 30 males aged 22-68 years. No significant difference was found between the strength patterns of the dominant and non-dominant hand. It is concluded that in the evaluation of hand strength under pathological conditions, the strength of the other hand should be a useful parameter.


Corrigendum: Ectopic Expression of the Grape Hyacinth (Muscari armeniacum) R2R3-MYB Transcription Factor Gene, MaAN2, Induces Anthocyanin Accumulation in Tobacco.
[This corrects the article on p. 965 in vol. 8, PMID: 28642775.].


Long-term effects of grass roots on gas permeability in unsaturated simulated landfill covers.
Landfill cover is a barrier that can reduce landfill gas emission. Vegetation could affect soil hydraulic properties of landfill cover, while its effects on gas permeability is not well understood. This paper investigated the effects of plant roots on the evolution of gas permeability (kg) in unsaturated landfill cover over a two-year period. One grass species (Cynodon dactylon) was selected for testing in the laboratory and there were six replications. Bare soil was used as a reference. kg was determined after 6, 15 and 24 months of grass growth. The test results show that with the increase of suction, kg increased linearly in log scale for both bare and grass-covered soils. kg of grass-covered can be lower or higher than that of bare soil, depending on the plant age. After 6 months, kg of grass-covered soil was smaller than that of bare soil by 85%, due to the root occupancy of soil pore space. However, after 15 and 24 months, kg of grass-covered soil increased by 2-3 orders of magnitude within the root zone over the suction range considered (2-86 kPa). After 2 years, kg of grass-covered soil was up to one order of magnitude higher than that in bare soil. It implies that mature vegetation is not beneficial for reducing gas emission in final landfill covers.


Complex formation between ferredoxin and ferredoxin-NADP+ reductase from Anabaena PCC 7119: cross-linking studies.
Ferredoxin-NADP+ reductase and ferredoxin from the cyanobacterium Anabaena PCC 7119 have been covalently cross-linked by incubation with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide. The covalent adduct, which shows a molecular mass consistent with a 1:1 stoichiometry of the two proteins, maintains nearly 60% of the NADPH-cytochrome c reductase activity of the enzyme saturated with ferredoxin and this value is considerably higher than when equimolar amounts of both proteins are assayed. No ternary complexes with Anabaena flavodoxin or horse heart cytochrome c were formed, suggesting that the binding site on the enzyme is the same for ferredoxin and flavodoxin and that ferredoxin-NADP+ reductase and cytochrome c bind at a common site on ferredoxin. In the noncovalent complex, titrated at pH 7, the oxidation-reduction potential of ferredoxin becomes 15 mV more negative and that of ferredoxin-NADP+ reductase 27 mV more positive compared to the proteins alone. When covalently linked, the midpoint potential of the enzyme has a value similar to that in the noncovalent complex, while the ferredoxin potential is 20 mV more positive compared to ferredoxin alone. The changes in redox potentials have been used to estimate the dissociation constants for the interaction of the different redox forms of the proteins, based on the value of 1.21 microM calculated for the oxidized noncovalent complex.


Erythropoietin prevented the decreased expression of aquaporin1-3 in ureteral obstructive kidneys in juvenile rats.
Urinary tract obstruction is associated with impaired renal urinary concentration; even after the release of the obstruction, patients still suffer from polyuria. It has been reported that the decreased expression of aquaporins (AQPs) is associated with postobstructive polyuria, and erythropoietin (EPO) can promote the recovery of decreased AQP2 expression induced by bilateral ureteral obstruction. However, whether EPO can promote the recovery of the expression of AQP1-3 after the release of unilateral ureteral obstruction (UUO) has not yet been reported. To investigate the effects of EPO treatment on the expression of renal AQP1-3 after the release of UUO. UUO was established in rats by 24-h temporary unilateral obstruction of renal ureters. Three days following EPO treatment, the kidneys were removed to determine the expression levels of AQP1-3, NLRP3, caspase-1, and IL-1β via semiquantitative immunoblotting and immunohistochemistry. EPO inhibited the expression of NLRP3, caspase-1, and IL-1β; reduced plasma creatinine and urea; and promoted the recovery of AQP1-3 expression in UUO rats. EPO treatment prevented the decreased expression of renal AQPs and the development of impaired urinary concentration capacity after the release of UUO, which may partially occur by way of anti-inflammasome effects. EPO treatment could prevent the decreased expression of renal water transporter proteins AQP1-3 and the development of impaired renal functions, which may be associated with its anti-inflammasome effects. EPO regulated the expression of renal water transporter proteins AQP1-3, which could provide the potential for the treatment of postobstructive polyuresis. EPO treatment could be one of the effective methods by participating in multiple dimensions for patients with obstructive nephropathy.


Extended-wear contact lenses and intraocular lenses for aphakic correction.
We evaluated extended-wear soft contact lens use in 128 aphakic eyes of 113 patients, 44 of whom had been unable to wear conventional contact lenses; 116 eyes (91%) have been successfully fitted and have worn the extended-wear lenses without significant complication. Eleven patients were unable to wear the lens or had to be discontinued for transient lens-related problems. In 103 eyes successfully fitted the lens is removed for cleaning less often than monthly. Ninety six of the 116 eyes fitted have visual acuity as good as, or better than, with aphakic correcting spectacles. The results obtained with the extended-wear soft contact lens are similar to those obtained with intraocular lenses, except for the recent high incidence of inflammation seen after intraocular lens insertion when using ethylene-oxide-sterilized lenses.


Polysaccharide extraction from Malva sylvestris and its anti-oxidant activity.
The effects of extraction temperature, extraction time, the ratio of water to raw material, and number of extraction on extraction yield of crude polysaccharides from the leaves of Malva sylvestris (MSLCP) were optimized by statistical analysis using response surface methodology. The response surface methodology (RSM) was used to optimize MSLCP extraction yield by implementing the CCD design. The experimental data obtained were fitted to a second-order polynomial equation using multiple regression analysis and also analyzed by appropriate statistical methods (ANOVA). Statistical analysis of the results showed that the linear and quadratic terms of these four variables had significant effects. The optimal conditions for higher extraction yield of MSLCP were extraction temperature: 90 °C, extraction time: 4 h, number of extraction: 2 and the ratio of water to raw material: 21. Under these conditions, the experimental yield was 8.377±0.38%, which is well in close agreement with the value predicted by the model 8.608%. The results demonstrated that MSLCP had strong scavenging activities in vitro on DPPH and hydroxyl radicals. Overall, MSLCP may have potential applications in the medical and food industries.


A high-sensitivity ultra-high performance liquid chromatography/high-resolution time-of-flight mass spectrometry (UHPLC-HR-TOFMS) method for screening synthetic cannabinoids and other drugs of abuse in urine.
The continuing emergence of designer drugs imposes high demands on the scope and sensitivity of toxicological drug screening procedures. An ultra-high performance liquid chromatography/high-resolution time-of-flight mass spectrometry (UHPLC-HR-TOFMS) method was developed for screening and simultaneous confirmation of both designer drugs and other drugs of abuse in urine samples in a single run. The method covered selected synthetic cannabinoids and cathinones, amphetamines, natural cannabinoids, opioids, cocaine and other important drugs of abuse, together with their main urinary metabolites. The database consisted of 277 compounds with molecular formula and exact monoisotopic mass; retention time was included for 192 compounds, and primary and secondary qualifier ion exact mass for 191 and 95 compounds, respectively. Following a solid-phase extraction, separation was performed by UHPLC and mass analysis by HR-TOFMS. MS, and broad-band collision-induced dissociation data were acquired at m/z range 50-700. Compound identification was based on a reverse database search with acceptance criteria for retention time, precursor ion mass accuracy, isotopic pattern and abundance of qualifier ions. Mass resolving power in spiked urine samples was on average FWHM 23,500 and mass accuracy 0.3 mDa. The mean and median cut-off concentrations determined for 75 compounds were 4.2 and 1 ng/mL, respectively. The range of cut-off concentrations for synthetic cannabinoids was 0.2-60 ng/mL and for cathinones 0.7-15 ng/mL. The method proved to combine high sensitivity and a wide scope in a manner not previously reported in drugs of abuse screening. The method's feasibility was demonstrated with 50 authentic urine samples.


Interaction between uric acid and endothelial dysfunction predicts new onset of diabetes in hypertensive patients.
Both uric acid and endothelial dysfunction are associated with new occurrence of type-2 diabetes but, at this moment, there is no evidence about a possible interaction between them. We tested, in untreated hypertensive patients, without clinical evidence of vascular damage, the hypothesis that serum uric acid and endothelial dysfunction may interact in predicting new diabetes. In 500 uncomplicated hypertensive non diabetic (ADA criteria) patients we evaluated endothelial function, by strain-gauge plethysmography, and uric acid. During the follow-up (median 87.1 months), there were 54 new cases of diabetes (1.8%/year). On univariate analysis, incident diabetes was inversely related with ACh-stimulated FBF (HR=0.65, 95%CI=0.52-0.82; P<0.001) and directly with serum CRP (HR=1.22, 95%CI=1.09-1.37; P<0.001), HOMA-index (HR=1.20, 95%CI=1.05-1.37; P=0.007), fasting insulin (HR=1.05, 95%CI=1.01-1.09; P=0.006) and age (HR=1.03, 95%CI=1.00-1.05; P=0.014). At multiple regression analysis, the interaction between ACh-stimulated FBF and uric acid resulted statistically significant. Similar results were observed for the interaction between FBF and CRP. Our data clearly demonstrate that the coexistence of both hyperuricemia and reduced endothelium-dependent vasodilation increases the risk to develop new diabetes in hypertensive patients. In addition, mild-inflammation seems to be the mediator of the interaction between endothelial dysfunction and uric acid.


Neutrophil-to-Lymphocyte Ratio Predicts Cancer Outcome in Locally Advanced Clear Renal Cell Carcinoma.
To evaluate the association of neutrophil-to-lymphocyte ratio (NLR) with recurrence-free survival (RFS) and overall survival (OS) in patients with locally advanced nonmetastatic clear cell renal cell carcinoma (ccRCC) undergoing radical nephrectomy. We retrospectively identified 880 nephrectomies performed between January 2009 and December 2016 in a single center, reviewed data from 478 radical nephrectomies for kidney tumors and identified 187 patients with locally advanced nonmetastatic ccRCC (pT3-T4 N0M0). NLR was obtained preoperatively and calculated by dividing absolute neutrophil count by absolute lymphocyte count. OS and RFS were evaluated by the Kaplan-Meier method. Cox proportional-hazards regression models were used to evaluate predictors of RFS and OS. Among 187 patients with ccRCC (mean age 63.4 ± 11.5 years; 118 [63.1%] male), the median follow-up was 48.7 months. On univariate analysis, in patients with Fuhrman nuclear grade of differentiation 3-4, the median time to recurrence was significantly shorter with NLR ≥ 4 than < 4 (24 vs. 55 months, P = .045). On multivariable analysis adjusted for NLR ≥ 4, among all variables analyzed (NLR, microvascular invasion, sarcomatoid differentiation, tumor size and body mass index), only nuclear grade of differentiation was an independent predictor of recurrence (hazard ratio 2.18; 95% confidence interval 1.07-4.92, P = .03). The 3-year OS had no statistically significant difference between patients with NLR ≥ 4 or < 4. For patients with locally advanced, nonmetastatic ccRCC, RFS was reduced with high nuclear grade of differentiation and high preoperative NLR. These findings suggest an association between higher NLR and worse outcomes in locally advanced ccRCC.


Macrophage and retinal pigment epithelium expression of angiogenic cytokines in choroidal neovascularization.
To determine the expression of angiogenic cytokines in macrophages and retinal pigment epithelium cells in choroidal neovascularization (CNV). Ten surgically-excised subfoveal CNV specimens and ten eye bank eyes with subfoveal CNV were routinely processed, serially sectioned, and immunostained for factor VIII (F8), CD68 (KP1), cytokeratin 18 (CK18), vascular endothelial growth factor (VEGF), tissue factor (TF), and monocyte chemotactic protein (MCP). The CNV was classified as "inflammatory active" (more inflammation than fibrosis) or "inflammatory inactive" (morefibrosis than inflammation). The immunostaining was graded as none, mild (+), moderate (++), or heavy (+++). Five additional surgically-excised CNV specimens were dual labeled with CK18/MCP or CD68/TF and confocal scanning laser microscopy was performed. Vascular endothelium, macrophages, and RPE expressed F8, KP1, and CK18 respectively. Macrophages expressed + to ++ VEGF and ++ to +++ TF; RPE expressed ++ to +++ VEGF and ++ to +++ MCP. Staining for angiogenic cytokines was stronger in inflammatory active versus inflammatory inactive CNV. RPE dual labeled for CK18/MCP and macrophages dual labeled for CD68/TF. This study shows that RPE cells express MCP, a cytokine involved with macrophage recruitment, and that macrophages express TF in CNV. Macrophages and RPE express VEGF, thus perpetuating angiogenesis. TF is involved with fibrin formation and provides a scaffold effect for growth of the CNV complex. CNV likely represents a dynamic process with inflammatory active and inflammatory inactive (involutional) stages.


Effect of different amounts of sodium intake for 4 months on calcium metabolism in normal and oophorectomized rats.
The effects of different amounts of salt intake on urinary calcium and hydroxyproline (OHP) excretion were studied in oophorectomized (O) and sham-operated (S) rats on normal calcium diet. Groups of O and S rats were given either tap water or 2, 6, or 18 g/liter of NaCl to drink. Urinary excretion of sodium, calcium, and OHP was monitored at 0, 2, and 4 months. Urinary excretion of calcium and OHP increased with increasing salt intake (P < 0.001 by ANOVA) in S and O groups. Oophorectomy did not have any additional effect on calcium or OHP excretion. We conclude that increased salt intake causes increased excretion of calcium and OHP and oophorectomy does not further aggravate the loss.


Sleep optimization to improve glycemic control in adults with type 1 diabetes: study protocol for a randomized controlled parallel intervention trial.
Despite improvements in treatment regimens and technology, less than 20% of adults with type 1 diabetes (T1D) achieve glycemic targets. Sleep is increasingly recognized as a potentially modifiable target for improving glycemic control. Diabetes distress, poor self-management behaviors, and reduced quality of life have also been linked to sleep variability and insufficient sleep duration. A significant gap of knowledge exists regarding interventions to improve sleep and the effects of sleep optimization on glycemic control in T1D. The purpose of this study is to determine the efficacy of a T1D-specific sleep optimization intervention (Sleep-Opt) on the primary outcomes of sleep variability, sleep duration, and glycemic control (A1C); other glycemic parameters (glycemic variability, time-in-range [TIR]); diabetes distress; self-management behaviors; quality of life; and other patient-reported outcomes in adults with T1D and habitual increased sleep variability or short sleep duration. A randomized controlled parallel-arm study will be employed in 120 adults (aged 18 to 65 years) with T1D. Participants will be screened for habitual sleep variability (> 1 h/week) or insufficient sleep duration (< 6.5 h per night). Eligible subjects will be randomized to the Sleep-Opt intervention group or healthy living attention control group for 12 weeks. A 1-week run-in period is planned, with baseline measures of sleep by actigraphy (sleep variability and duration), glycemia (A1C and related glycemic measures: glycemic variability and TIR using continuous glucose monitoring), and other secondary outcomes: diabetes distress, self-management behaviors, quality of life, and additional patient-reported outcomes. Sleep-Opt is a technology-assisted behavioral sleep intervention that we recently developed that leverages the rapidly increasing public interest in sleep tracking. Our behavioral intervention employs four elements: a wearable sleep tracker, didactic content, an interactive smartphone application, and brief telephone counseling. The attention control group will participate in a healthy living information program. Baseline measures will be repeated at midpoint, program completion, and post-program (weeks 6, 12, and 24, respectively) to determine differences between the two groups and sustainability of the intervention. A better understanding of strategies to improve sleep in persons with T1D has the potential to be an important component of diabetes. Clinical Trial Registration: NCT04506151 .


Variations in content of care in a family medicine residency relating to types of insurance coverage.
The content of care in a family practice residency program was analyzed using a microcomputer information system. The distribution of recorded diagnoses in the training program was found to be very similar to results of two national studies of family medicine. Despite this overall similarity, important differences were found when distributions for patients with six types of insurance coverages were analyzed separately. This study demonstrates the potential effect of insurance coverage on the clinical content of family medicine. As the health care system changes, residency programs will need to remain adaptable to maintain patient bases reflecting the broad content of family medicine.


The uniqueness of elderly care: registered nurses' experience as preceptors during clinical practice in nursing homes and home-based care.
The expected shortage of registered nurses with an advanced degree as specialists in geriatric care or gerontology is imminent. Previous studies report that clinical practice where student nurses are supervised by registered nurses has a direct impact on how students perceive nursing as a profession and future career choice. Considering the anticipated need for well-educated and specialised nurses it is therefore, relevant as well as necessary to describe clinical learning with a focus on preceptorship in geriatric nursing care. This paper is a report of a study describing registered nurses' experience of precepting undergraduate student nurses during clinical practice in nursing homes and home-based care. A qualitative design, based on seven focus group interviews, was employed with 30 registered nurses with preceptor experience from nursing homes and home-based care for the elderly. Our findings present three precepting strategies that are unique to elderly care: preparing students for end of life care, facilitating a respectful approach to the older person and promoting creativity and independent work. The findings are discussed using a socio-cultural perspective and illustrate how communities of elderly practice can be valuable learning environments.


Characterization of a heme-protein responsive to hypoxia in Paracoccidioides brasiliensis.
Oxygen is fundamental to the life of aerobic organisms and is not always available to Paracoccidioides cells. During the life cycle stages, reduced oxygen levels directly affect general metabolic processes and oxygen adaptation mechanisms may play a fundamental role on fungal ability to survive under such condition. Heme proteins can bind to oxygen and participate in important biological processes. Several fungi, including Paracoccidioides, express a heme-binding globin (fungoglobin - FglA) presumable to regulate fungal adaptation to hypoxia. However, the characterization of fungoglobin in Paracoccidioides spp. has not yet been performed. In this study, we predicted the structure of fungoglobin and determined its level of expression during hypoxic-mimetic conditions. Genomic screening revealed that the fungoglobin gene is conserved in all species of the Paracoccidioides genus. Molecular modeling showed biochemical and biophysical characteristics that support the hypothesis that FglA binds to the heme group and oxygen as well. The fungoglobin transcript and proteins are expressed at higher levels at the early treatment time, remaining elevated while oxygen is limited. A P. brasiliensis fglA knockdown strain depicted reduced growth in hypoxia indicating that this protein can be essential for growth at low oxygen. Biochemical analysis confirmed the binding of fungoglobin to heme. Initial analyzes were carried out to establish the relationship between FlglA and iron metabolism. The FglA transcript was up regulated in pulmonary infection, suggesting its potential role in the disease establishment. We believe that this study can contribute to the understanding of fungal biology and open new perspectives for scientific investigations.


Nanostructured Biomaterials for Tissue Repair and Anti-Infection.
Biomaterials play a vital role in regenerative medicine, aiming to regenerate and replace lost/dysfunctional tissues [...].


Discrimination of raw and processed Dipsacus asperoides by near infrared spectroscopy combined with least squares-support vector machine and random forests.
Most herbal medicines could be processed to fulfill the different requirements of therapy. The purpose of this study was to discriminate between raw and processed Dipsacus asperoides, a common traditional Chinese medicine, based on their near infrared (NIR) spectra. Least squares-support vector machine (LS-SVM) and random forests (RF) were employed for full-spectrum classification. Three types of kernels, including linear kernel, polynomial kernel and radial basis function kernel (RBF), were checked for optimization of LS-SVM model. For comparison, a linear discriminant analysis (LDA) model was performed for classification, and the successive projections algorithm (SPA) was executed prior to building an LDA model to choose an appropriate subset of wavelengths. The three methods were applied to a dataset containing 40 raw herbs and 40 corresponding processed herbs. We ran 50 runs of 10-fold cross validation to evaluate the model's efficiency. The performance of the LS-SVM with RBF kernel (RBF LS-SVM) was better than the other two kernels. The RF, RBF LS-SVM and SPA-LDA successfully classified all test samples. The mean error rates for the 50 runs of 10-fold cross validation were 1.35% for RBF LS-SVM, 2.87% for RF, and 2.50% for SPA-LDA. The best classification results were obtained by using LS-SVM with RBF kernel, while RF was fast in the training and making predictions.


Attempted expression of a human initiator tRNA gene in Saccharomyces cerevisiae.
In attempts to overproduce the wild type and, eventually, mutant human initiator methionine tRNAs for use in structure-function relationship studies, we have investigated the expression of the wild type human initiator tRNA gene in the yeast Saccharomyces cerevisiae, both in vitro and in vivo. We find that the yeast extract, while capable of accurately transcribing several yeast tRNA genes, does not transcribe the human initiator tRNA gene. In addition, when the human initiator tRNA gene is introduced into yeast as part of a 2 mu vector, no expression of the human tRNA gene was detected. A yeast alanine tRNA gene similarly introduced into yeast is expressed efficiently. The block in expression of the human tRNA gene is at the level of transcription and not processing. The yeast cell-free extract can accurately process precursors of the same human initiator tRNA made in a HeLa cell-free extract. Surprisingly, although the human tRNA gene has essentially the same intragenic control elements as the yeast initiator tRNA gene, the human tRNA gene competes extremely poorly for transcription factors in yeast extracts. In the course of screening a yeast DNA bank for initiator tRNA clones we have isolated and sequenced three yeast tRNA genes corresponding to glycine, alanine, and aspartic acid tRNAs. The sequence of glycine tRNA gene differs from the published tRNA sequence in having an additional nucleotide in the variable loop. The alanine tRNA gene codes for a new tRNA. All three genes are transcriptionally active in yeast extracts.


C [bond] H activation by cationic platinum(II) complexes: ligand electronic and steric effects.
A series of bis(aryl)diimine-ligated methyl complexes of Pt(II) with various substituted aryl groups has been prepared. The cationic complexes [(ArN=CR [bond] CR=NAr)PtMe(L)](+)[BF(4)](-) (Ar = aryl; R = H, CH(3); L = water, trifluoroethanol) react smoothly with benzene at approximately room temperature in trifluoroethanol solvent to yield methane and the corresponding phenyl Pt(II) cations, via Pt(IV)-methyl-phenyl-hydrido intermediates. The reaction products of methyl-substituted benzenes suggest an inherent reactivity preference for aromatic over benzylic C [bond] H activation, which can however be overridden by steric effects. For the reaction of benzene with cationic Pt(II) complexes bearing 3,5-disubstituted aryl diimine ligands, the rate-determining step is C [bond] H activation, whereas for the more sterically crowded analogues with 2,6-dimethyl-substituted aryl groups, benzene coordination becomes rate-determining. This switch is manifested in distinctly different isotope scrambling and kinetic deuterium isotope effect patterns. The more electron-rich the ligand is, as assayed by the CO stretching frequency of the corresponding carbonyl cationic complex, the faster the rate of C [bond] H activation. Although at first sight this trend appears to be at odds with the common description of this class of reaction as electrophilic, the fact that the same trend is observed for the two different series of complexes, which have different rate-determining steps, suggests that this finding does not reflect the actual C [bond] H activation process, but rather reflects only the relative ease of benzene displacing a ligand to initiate the reaction; that is, the change in rates is mostly due to a ground-state effect. The stability of the aquo complex ground state in equilibrium with the solvento complex increases as the diimine ligand is made more electron-withdrawing. Several lines of evidence, including the mechanism of degenerate acetonitrile exchange for the methyl-acetonitrile Pt(II) cations in alcohol solvents, suggest that associative substitution pathways operate to get the hydrocarbon substrate into, and out of, the coordination sphere; that is, the mechanism of benzene substitution proceeds by a solvent (TFE)-assisted associative pathway.


The effect of protein supplement concentration in embryo transfer medium on clinical outcome of IVF/ICSI cycles: a prospective, randomized clinical trial.
The aim of this prospective, randomized clinical trial (RCT) was to evaluate whether the supplemental protein concentration in embryo transfer (ET) medium affects the clinical outcomes in IVF-ET. A total of 750 patients undergoing IVF-ET who met the inclusion criteria were randomly divided into three groups, according to the concentration of synthetic serum substitute (SSS) in ET medium as follows: 10% (Group A), 20% (Group B) and 50% (Group C). The patient characteristics and embryology data were all similar among the groups. The rates of implantation, clinical pregnancy and live birth were compared. Clinical pregnancy (44.61%, 48.79% and 45.49%), multiple pregnancy (24.18%, 28.71% and 25.0%), implantation (28.21%, 30.68% and 29.86%) and live birth (41.67%, 43.96% and 41.70%) rates in the three groups (A, B and C, respectively) showed no significant differences. This RCT demonstrates that supplemental protein concentration in the ET medium does not affect the treatment outcomes in IVF-ET. There was no statistical evidence to support the hypothesis that supplemental protein concentration in the ET medium influences treatment outcomes in IVF-ET.


In vivo evaluation of an implantable portal pump system for augmenting liver perfusion.
Increasing portal inflow in cirrhosis using a mechanical pump reduces portal venous pressure and improves liver function. A pump has been developed for portal vein implantation in human cirrhosis. This study describes the initial in vivo evaluation in a porcine model. Five Large White pigs underwent laparotomy and exposure of the liver. Flow in the hepatic artery, portal vein and hepatic microcirculation was monitored continuously. Hepatic tissue oxygenation was measured by near-infrared spectroscopy. After baseline measurements the pump was inserted into the portal vein. Pump flow rate was then increased stepwise to 50 per cent over the baseline value for a period of 2 h. The pump was then stopped for 20 min and left in situ while continuing to collect systemic and hepatic haemodynamic data. The animal was killed and biopsies for histological examination were taken from the liver, small intestine and spleen. The baseline total hepatic blood flow was 626(39) ml/min; the hepatic artery supplied 18.4(2.1) per cent and the portal vein 81.6(2.1) per cent. The pump was inserted successfully in all animals without surgical complications. During surgical insertion of the pump, the temporary portal vein occlusion resulted in a significant rise in hepatic artery blood flow (22(3) per cent; P < 0.01 versus baseline). Portal vein flow was augmented by pumping; there was a significant correlation between the pump motor speed and portal vein flow (P < 0.0001). This inflow correlated directly with flow in the hepatic microcirculation and hepatic tissue oxygenation (P < 0.001). The pump ran satisfactorily throughout the study. Histological examination revealed no evidence of structural damage to the liver or ischaemic changes in the small intestine or spleen. It is technically possible and safe to insert an implantable pump in the portal vein. Portal venous blood flow can be increased up to 50 per cent with a resultant increase in flow in the hepatic microcirculation and hepatic oxygenation and without adverse effects on either hepatic or systemic haemodynamics.


The late results of antero-lateral cordotomy for pain relief.
The operation of antero-lateral cordotomy was carried out on 56 patients with intractable pain between 1968 and 1978. The follow-up of these patients was continued for at least three years or until death to determine the late success of this procedure. Of the 33 patients who underwent surgery for malignant pain 95% of survivors had effective relief on discharge from hospital, the success rate falling to 73% at six months, and 55% at one year of follow-up. The operation was judged successful for patients with malignant disease because of short life expectancy. Thirteen patients had chronic pain from non-malignant conditions, and 85% obtained initial relief, the success rate falling to 35% at one year, and 20% at three years of follow-up. Two patients died from respiratory failure, giving an operative mortality of 3.5%. The results and complications of open cordotomy are compared with those of the percutaneous method, and the role of this procedure discussed in relation to alternative stimulatory analgesic procedures.


Correction: Advances and potential pitfalls of oncolytic viruses expressing immunomodulatory transgene therapy for malignant gliomas.
A Correction to this paper has been published: https://doi.org/10.1038/s41419-020-2696-5.


Absence of interhemispheric connections of area 17 during development in the monkey.
Our understanding of the development of cortical connectivity largely stems from studies of the ontogeny of interhemispheric pathways in carnivores, rodents and lagomorphs. Early in development, cortical neurons projecting to the contralateral hemisphere through the corpus callosum (callosal projection neurons) have a widespread distribution. As maturation proceeds, callosal projection neurons become restricted to those cortical regions that are connected in the adult. In newborn cats and rats, for example, callosal projection neurons are not restricted to the 17-18 border as in the adult, but are found throughout areas 17 and 18. The macaque monkey is an exception, because at birth it has an adult-like distribution of callosal projection neurons in area 18, with practically none in area 17. Here we show that whereas area 17 is devoid of interhemispheric connections throughout prenatal development, the distribution of callosal projection neurons in area 18 shows the common sequence of an early widespread distribution followed by regression. The absence of callosal projection neurons in area 17 throughout ontogeny may well be a feature unique to Old World primates.


A novel and enantioselective epoxide hydrolase from Aspergillus brasiliensis CCT 1435: purification and characterization.
A novel epoxide hydrolase from Aspergillus brasiliensis CCT1435 (AbEH) was cloned and overexpressed in Escherichia coli cells with a 6xHis-tag and purified by nickel affinity chromatography. Gel filtration analysis and circular dichroism measurements indicated that this novel AbEH is a homodimer in aqueous solution and contains the typical secondary structure of an α/β hydrolase fold. The activity of AbEH was initially assessed using the fluorogenic probe O-(3,4-epoxybutyl) umbelliferone and was active in a broad range of pH (6-9) and temperature (25-45°C); showing optimum performance at pH 6.0 and 30°C. The Michaelis constant (KM) and maximum rate (Vmax) values were 495μM and 0.24μM/s, respectively. Racemic styrene oxide (SO) was used as a substrate to assess the AbEH activity and enantioselectivity, and 66% of the SO was hydrolyzed after only 5min of reaction, with the remaining (S)-SO ee exceeding 99% in a typical kinetic resolution behavior. The AbEH-catalyzed hydrolysis of SO was also evaluated in a biphasic system of water:isooctane; (R)-diol in 84% ee and unreacted (S)-SO in 36% ee were produced, with 43% conversion in 24h, indicating a discrete enantioconvergent behavior for AbEH. This novel epoxide hydrolase has biotechnological potential for the preparation of enantiopure epoxides or vicinal diols.


[Occupational and non-occupational risk factors in bladder cancer patients in an industrialized area located in former East-Germany].
Several occupational carcinogens are metabolized by polymorphic enzymes. The distribution of the polymorphic enzymes N-acetyltransferase 2 (NAT2; substrates: aromatic amines), glutathione S-transferase M1 (GSTM1; substrates: e. g., reactive metabolites of polycyclic aromatic hydrocarbons), and glutathione S-transferase T1 (GSTT1; substrates: small molecules with 1 - 2 carbon atoms) were investigated. At the urological department in Lutherstadt Wittenberg, 136 patients with a histologically proven transitional cell cancer of the urinary bladder were investigated for all occupations performed for more than 6 months. Several occupational and non-occupational risk factors were asked. The genotypes of NAT2, GSTM1, and GSTT1 were determined from leucocyte DNA by PCR. Compared to the general population in Middle Europe, the percentage of GSTT1 negative persons (22.1 %) was ordinary; the percentage of slow acetylators (59.6 %) was in the upper normal range, while the percentage of GSTM1 negative persons (58.8 %) was elevated in the entire group. Shifts in the distribution of the genotypes were observed in subgroups who had been exposed to asbestos (6/6 GSTM1 negative, 5/6 slow acetylators), rubber manufacturing (8/10 GSTM1 negative), and chlorinated solvents (9/15 GSTM1 negative). The overrepresentation of GSTM1 negative bladder cancer patients also in this industrialized area and more pronounced in several occupationally exposed subgroups points to an impact of the GSTM1 negative genotype in bladder carcinogenesis.


[Neuro-anatomic activations of prepotent responses in schizophrenia in Hayling's task].
In schizophrenia, alteration in the prefrontal cortex can induce some deficiencies of the executive functions, and among them errors in inhibition of prepotent responses. This type of inhibitory processes was called "restraint function" by Hasher et al. It implies a conscious and voluntary inhibition which demands attentional resources. Among the tasks exploring this function, the Hayling completion sentence task (Burgess and Shallice) appears to be the most specific. Moreover, healthy subjects performing this task in functional magnetic resonance imaging (fMRI) show activation of the prefrontal cortex. In this study, we investigated inhibitory processes in schizophrenic patients using two versions of the Hayling completion sentence task, a behavioural version and an fMRI version in order to assess both performance levels and brain correlates of inhibitory processes. Forty-eight schizophrenic participants according to DSM-IV, (mean age: 32.8, S.D. 7.7), stabilized for at least one month, receiving antipsychotic medication and with IQ higher than 70 (mean: 96.86, S.D. 20.67) and education level (mean: 11.15, S.D. 3.26) participated in the behavioural study. They were matched on age (mean: 33.8, S.D. 7.6) and education level (mean: 12.28, S.D. 2.87) with thirty-two healthy controls. Nineteen of schizophrenic participants (mean age: 33, S.D. 6.9 and IQ: 99, S.D. 10.74) were assessed by an fMRI adaptation of the Hayling task, matched with 12 controls (mean: 33.9, S.D. 7.3). All the participants had to perform the Hayling task and a speed accuracy task. The Hayling task consists in sentences for which the last word is missing. In the initiation condition, the participants had to complete the sentence with the appropriate word, whereas in inhibition condition the participants had to complete the sentence with inappropriate and unrelated words. Compared to controls, schizophrenics showed an increased number of errors in the inhibition of prepotent responses associated with increased reaction times, even when considering information processing speed. fMRI results showed fairly similar frontal activations in both groups. Nevertheless, schizophrenic patients presented principally large activations in dorsolateral and ventrolateral frontal cortex, the superior frontal sulcus, the frontal pole and the premotor cortex, and stronger activations (bilateral) in the posterior parietal cortex. Control subjects demonstrated a network of deactivated brain regions whereas the schizophrenics did not. Our results are in favour of poorer efficacy of restraint function, sometimes comprising impairment of inhibitory processes inducing errors in schizophrenics. This deficiency might be considered as insufficiency in attentional resources and/or in working memory. Hence patients cannot simultaneously restrain prepotent response and find appropriate controlled strategy for correct completion of the task. Moreover, bilateral patterns of parietal hyperactivation and absence of patterns of deactivation seem also in favour of an attentional hypothesis. The Hayling task might be interesting for assessment of inhibitory processes in schizophrenia.


Promotion of nerve regeneration in peripheral nerve by short-course FK506 after end-to-side neurorrhaphy.
To discuss the feasibility of peripheral nerve injury treated by end-to-side neurorrhaphy in clinic and to evaluate the effect of short-course FK506 on promoting nerve regeneration after end-to-side neurorrhaphy. Thirty adult male Sprague Dawley rats were randomly divided into 3 groups: Group A, 10 rats received end-to-end anastomosis; Group B, 10 rats received end-to-side neurorrhaphy; Group C, 10 rats received the same operation as Group B. After operation, rats in Groups B and C received muscle injection with saline water (1 mg/kg x d(-1)) and FK506 (1 mg/kg x d(-1)), respectively, both for 4 wk. Histological and morphological examinations were performed 12 wk after the operation. In the 2nd, 4th, 6th, 8th, and 12th wk after operation, function recovery analysis was performed. The results of histological and immunochemistry study (the total number of Schwann cells and the axon numbers at the distal stump of the peroneal nerve, wet weight of extensor digitorum longus muscle) suggested that there were significant differences between Group B (saline water group) and Group C (FK506 group) (P < 0.05), also between Group A (end-to-end group) and Group C (P < 0.05). There were statistically significant differences in function recovery (peroneal functional index and sciatic functional index) between Groups B and C (P < 0.05) and also between Groups A and C (P < 0.05). End-to-side repair combined with FK506 has a potential for application in selected cases of peripheral nerve injury in clinic.


Inspiratory muscle training is used in some intensive care units, but many training methods have uncertain efficacy: a survey of French physiotherapists.
How common is inspiratory muscle training by physiotherapists in the intensive care unit (ICU)? Which patients receive the training? What methods are used to administer the training? Is maximal inspiratory pressure used to evaluate the need for the training and the patient's outcome after training? Cross-sectional survey of all ICUs in France. Two hundred and sixty-five senior physiotherapists. The response rate was 99% among eligible units. Therapist experience in ICU was significantly associated with the use of inspiratory muscle training (p=0.02). Therapists mainly used inspiratory muscle training either systematically or specifically in patients who failed to wean from mechanical ventilation. The training was used significantly more in non-sedated patients (p<0.0001). The most commonly nominated technique that respondents claimed to use to apply the training was controlled diaphragmatic breathing (83% of respondents), whereas 13% used evidence-based methods. Among those who applied some form of inspiratory muscle training, 16% assessed maximal inspiratory pressure. Six respondents (2%, 95% CI 1 to 5) used both an evidence-based method to administer inspiratory muscle training and the recommended technique for assessment of inspiratory muscle strength. Most physiotherapists in French ICUs who apply inspiratory muscle training use methods of uncertain efficacy without assessment of maximal inspiratory pressure. Further efforts need to be made in France to disseminate information regarding evidence-based assessment and techniques for inspiratory muscle training in the ICU. The alignment of inspiratory muscle training practice with evidence could be investigated in other regions.


It is time to beelieve the CD1a hype!
Conventional T cells have historically been linked to exacerbating allergy. By efficiently generating primarily TH 2 cells, allergens skew the immune response to produce IL-4, IL-13, and IgE. Previously, CD1a-responsive T cells were shown to functionally respond to bee and wasp venom allergens. In this issue of the European Journal of Immunology, Subramaniam et al. [Eur. J. Immunol. 2016. 46: 242-252] show that more functionally active CD1a-restricted cells are present in bee venom-allergic patients than in healthy patients. Additionally, the authors show that these cells are not as frequently found in individuals receiving venom immunotherapy. Consequently, this study implicates CD1a-reactive cells as the primary responders to venom allergy, which considerably regulate the downstream immune response.


The protective function of the compact silk nest of social Stegodyphus spiders (Araneae, Eresidae).
This study investigates the suggested protective function of the compact silken nest of two species of social Stegodyphus spiders (S. dumicola and S. mimosarum), as a possible ultimate factor for their sociogenesis. Being inhabitants of African dry thornbush country, these spiders are endangered by overheating and desiccation. In the laboratory, both species were found to avoid temperatures >40° C. In the field, temperature in the nest between 7:00 and 21:00 h tends to be higher than air-temperature outside, and between 13:00 and 15:00 h even tends to exceed 40° C. The nest thus is of no value in temperature regulation. Nor is it effective in protecting the spiders from desiccation: Both species have a body water content of 65.2±3.8% and are extremely desiccation resistant; they survived 9 days at 37°C in an exciccator with P2O5, with a daily average % liveweight reduction of 4.94(±1.1). In the field, relative humidity inside the nest between 11:00 and 19:00 h tends to be lower than that of the air outside. Inspection of burnt areas showed that the nest does not protect the spiders from bushfire. The nest does protect from wind, hail, and direct sun-radiation; but available natural retreats, or a simple silken shield, or the funnel-shaped silk tube inhabited by solitary Stegodyphus, have the same effect.


Genetic variations of four immunodominant antigens of Babesia gibsoni isolated from dogs in southwest Japan.
Babesia gibsoni is a tick-borne apicomplexan parasite of dogs that often causes fever and hemolytic anemia. Previous reports have shown that the apical membrane antigen 1 (BgAMA1), the 50 kDa surface antigen (BgP50), the secreted antigen 1 (BgSA1), and the thrombospondin-related adhesive protein (BgTRAP) are promising diagnostic antigens and vaccine candidates against B. gibsoni. In the present study, we investigated the genetic polymorphisms and natural selection of these four genes of B. gibsoni isolated from dogs in southwest Japan. The prediction B-cell epitopes showed high antigenic score in the insert and indel regions of BgSA1 and BgTRAP. Sequence analyses have revealed that BgAMA1 had the highest nucleotide diversity, followed by BgP50, BgSA1 and BgTRAP. Meanwhile, the Tajima's D value test suggested balancing selection for BgAMA1 and BgP50. However, BgSA1 and BgTRAP have purifying selection making them potential vaccine candidate and diagnostic antigens since they are highly conserved. Our findings provide the genetic basis for designing and testing the efficacy of diagnostic antigens as well as vaccine candidates against B. gibsoni.


Remifentanil postconditioning improves global cerebral ischemia-induced spatial learning and memory deficit in rats via inhibition of neuronal apoptosis through the PI3K signaling pathway.
Global cerebral ischemia followed by reperfusion, which leads to extensive neuronal damage, particularly the neurons in the hippocampal CA1 region. Apoptosis is one of the major mechanisms that lead to neuronal death after cerebral ischemia and reperfusion. The neuroprotective effects of remifentanil preconditioning against cerebral ischemia/reperfusion injury have been recently reported. Here we investigated whether remifentanil postconditioning exerts neuroprotective effects against global cerebral ischemia/reperfusion injury in rats and its potential mechanisms. Global cerebral ischemia was performed via 10 min of four-vessel occlusion. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling positive cells and expression of Bcl-2 and Bax in the hippocampal CA1 region were assessed after reperfusion. Morris water maze task was used to quantify spatial learning and memory deficits after reperfusion. We found remifentanil postconditioning markedly improved the spatial learning and memory as well as attenuated neuronal apoptosis in hippocampus caused by cerebral ischemia/reperfusion injury. In addition, remifentanil postconditioning enhanced the expression of anti-apoptotic gene Bcl-2 while suppressed the expression of pro-apoptotic gene Bax in hippocampal CA1 region. However, the neuroprotective effects of remifentanil postconditioning were abolished by pretreatment of the PI3K inhibitor LY294002. The results suggest that remifentanil postconditioning exhibits neuroprotective effects against global cerebral ischemia/reperfusion injury in rats, and its mechanisms might involve inhibition of neuronal apoptosis through the PI3K pathway.


Quantitative differences in smooth pursuit and saccadic eye movements.
Recently it has been suggested that smooth pursuit (SP) and saccadic (SAC) eye movements share many common brain substrates in the planning and control of eye movements (Krauzlis in J Neurophysiol 91:591-603, 2004). Evidence is mounting that these two types of eye movements may also share similar mechanisms used to drive both reactive and predictive eye movement responses (Missal and Keller in J Neurophysiol 88:1880-1892, 2002, Keller and Missal in Ann NY Acad Sci 1004:29-39, 2003). The objective of this study was to quantify these similarities by establishing whether the behavioural response properties of human eye movements to predictive (PRD) and randomized (RND) conditions are quantitatively similar for both SP and SAC in directly comparable paradigms. Two previous studies have attempted to evaluate the coordination and motor preparation time of SP and saccadic eye movements (Erkelens in Vis Res 46:163-170, 2006; Joiner and Shelhamer in Exp Brain Res, Epub ahead of print, 2006). However, no previous study has quantitatively evaluated PRD and RND conditions to discretely presented SP and SAC tasks. We used simple SAC and SP paradigms in blocks of PRD and RND presentations, with eye movements monitored throughout using an IR-limbus eye-tracking system (Skalar). Twelve normal subjects (aged between 20 and 39 years) participated in the study which took place over two recording sessions, on two separate days. Data were analysed for two main comparable descriptive statistics: latency and eye velocity/displacement gain. The results presented here support the notion that SP and SAC share common brain substrates/mechanisms in the generation of responses to PRD and RND visual targets but differ in the movement preparation time.


Occurrence, distribution, and associations of essential and non-essential elements in the medicinal and edible fungus "Fuling" from southern China.
In Asian countries, the sclerotia of the wild-grown fungus Pachyma hoelen ("Fuling"), have been used as food and as medicinal products for centuries. To close the knowledge gaps about the value and possible environmental impacts, the occurrence, distribution, and associations of a range of elements (Ag, Al, As, Ba, Cd, Co, Cr, Cs, Cu, Li, Mg, Mn, Ni, Pb, Rb, Sb, Sr, Tl, U, V, and Zn) were studied in the inner (core) and outer (shell) morphological parts of the sclerotia from a diverse collection in Southern China. Quality of forest and agricultural soil in terms of a geogenic element source and composition can be considered as the main factor determining the occurrence of minerals in sclerotia through the host wood, largely of Pinus yunnanensis, while the anthropogenic impact (basically at remote rural areas of cultivation) in Southern China was negligible. In general, the mean concentration of each element in the outer part was significantly higher than that in the inner part (t-test, p < 0.01), except for Ag. The concentration of a given element in the outer part tended to have a positive relationship with that in the inner part, except for Cu, Se, Ag, and Zn. The elements in different morphological parts of sclerotia present different relation patterns. Compared to the outer part, there were stronger associations of elements in the inner part, suggesting homeostatic regulation of multiple elements in the inner parts. Further study on the sclerotia, infected wood substrate, and surrounding soil from a range of wild sample collections and intentional cultivation should provide a more complex view and allow assessment of the relationship between minerals and bioactive organic compounds produced by P. hoelen.


Obstructive azoospermia: reconstructive techniques and results.
Obstructive azoospermia is a common cause of male infertility and can result from infection, congenital anomalies, or iatrogenic injury. Microsurgical vasal reconstruction is a suitable treatment for many cases of obstructive azoospermia, although some couples will require sperm retrieval paired with in-vitro fertilization. The various causes of obstructive azoospermia and recommended treatments will be examined. Microsurgical vasovasostomy and vasoepididymostomy will be discussed in detail. The postoperative patency and pregnancy rates for surgical reconstruction of obstructive azoospermia and the impact of etiology, obstructive interval, sperm granuloma, age, and previous reconstruction on patency and pregnancy will be reviewed.


3H-Spiroperidol labels dopamine receptors in pituitary and brain.
3H-Spiroperidol of high specific radioactivity labels dopamine receptors in membranes of bovine caudate nucleus and anterior pituitary. The saturation and kinetic properties of 3H-spiroperidol binding are similar in the two tissues. In both caudate and pituitary 3H-spiroperidol displays very high affinity with a dissociation constant of 0.2-0.3 nM. The relative potencies of numerous dopamine agonists and antagonists in competing for 3H-spiroperidol binding are closely similar in anterior pituitary and caudate.


Cyclic AMP-stimulated protein kinases at brain synaptic junctions.
We have examined endogenous cyclic AMP-stimulated phosphorylation of subcellular fractions of rat brain enriched in synaptic plasma membranes (SPM), purified synaptic junctions (SJ), and postsynaptic densities (PSD). The analyses of these fractions are essential to provide direct evidence for cyclic AMP-dependent endogenous phosphorylation at discrete synaptic junctional loci. Protein kinase activity was measured in subcellular fractions using both endogenous and exogenous (histones) proteins as substrates. The SJ fraction possessed the highest kinase activity toward endogenous protein substrates, 5-fold greater than SPM and approximately 120-fold greater than PSD fractions. Although the kinase activity as measured with histones as substrates was only slightly higher in SJ than SPM fractions, there was a marked preference of kinase activity toward endogenous compared to exogenous substrates in SJ fractions but in SPM fractions. Although overall phosphorylation in SJ fractions was increased only 36% by 5 micron cyclic AMP, there were discrete proteins of Mr = 85,000, 82,000, 78,000, and 55,000 which incorporated 2- to 3-fold more radioactive phosphate in the presence of cyclic AMP. Most, if not all, of the cyclic AMP-independent kinase activity is probably catalyzed by catalytic subunit derived from cyclic AMP-dependent kinase, since the phosphorylation of both exogenous and endogenous proteins was greatly decreased in the presence of a heat-stable inhibitor protein prepared from the soluble fraction of rat brain. The specific retention of SJ protein kinase(s) activity during purification and their resistance to detergent solubilization was achieved by chemical treatments which produce interprotein cross-linking via disulfide bridges. Two SJ polypeptides of Mr = 55,000 and 49,000 were photoaffinity-labeled with [32P]8-N3-cyclic AMP and probably represent the regulatory subunits of the type I and II cyclic AMP-dependent protein kinases. The protein of Mr = 55,000 was phosphorylated in a cyclic AMP-stimulated manner suggesting autophosphorylation as previously observed in other systems.


Genome-Wide Assessment of Runs of Homozygosity in Chinese Wagyu Beef Cattle.
Runs of homozygosity (ROH) are continuous homozygous regions that generally exist in the DNA sequence of diploid organisms. Identifications of ROH leading to reduction in performance can provide valuable insight into the genetic architecture of complex traits. Here, we evaluated genome-wide patterns of homozygosity and their association with important traits in Chinese Wagyu beef cattle. We identified a total of 29,271 ROH segments from 462 animals. Within each animal, an average number of ROH was 63.36 while an average length was 62.19 Mb. To evaluate the enrichment of ROH across genomes, we initially identified 280 ROH regions by merging ROH events across all individuals. Of these, nine regions containing 154 candidate genes, were significantly associated with six traits (body height, chest circumference, fat coverage, backfat thickness, ribeye area, and carcass length; p < 0.01). Moreover, we found 26 consensus ROH regions with frequencies exceeding 10%, and several regions overlapped with QTLs, which are associated with body weight, calving ease, and stillbirth. Among them, we observed 41 candidate genes, including BCKDHB, MAB21L1, SLC2A13, FGFR3, FGFRL1, CPLX1, CTNNA1, CORT, CTNNBIP1, and NMNAT1, which have been previously reported to be related to body conformation, meat quality, susceptibility, and reproductive traits. In summary, we assessed genome-wide autozygosity patterns and inbreeding levels in Chinese Wagyu beef cattle. Our study identified many candidate regions and genes overlapped with ROH for several important traits, which could be unitized to assist the design of a selection mating strategy in beef cattle.


The changes in the release level of polyunsaturated fatty acids (ω-3 and ω-6) and lipids in the untreated and water-soaked chia seed.
Despite recent studies on health benefits of chia seed owing to its high content of ω-3 fatty acids, little work has been conducted on extractability of its nutrients. We examined the effect of soaking chia seed in water on the extractability of its omega fatty acids and lipids. State-of-the-art mass spectrometry techniques including GC-MS, LC-MS, and MALDI-MSI were utilized to identify and determine the spatial distribution of omega fatty acids and lipids in chia seed. Results showed that 24 h soaking in water improves the extractability of omega fatty acids and the ω-6:ω-3 ratio. Increase in the release levels of triacylglycerols and diacylglycerols and reduction in the release levels of phosphatidylcholines are envisaged to be the result of cell wall weakening and consequently availability of lipids for extraction. Results of MALDI-MSI show that highly abundant lipid species are mainly localised in the chia seed endosperm rather than its mucilage.


Chronic administration of the oral hypoglycaemic agent diphenyleneiodonium to rats. An animal model of impaired oxidative phosphorylation (mitochondrial myopathy).
Daily subcutaneous administration of the oral hypoglycaemic agent, diphenyleneiodonium at a low dose (1.5 mg/kg body weight) over a 4-5 week period resulted in a normoglycaemic stable animal model of impaired oxidative phosphorylation in the rat. Diphenyleneiodonium specifically inhibits NAD-linked mitochondrial oxidation [Bloxham, Biochem. Soc. Trans. 7, 103 (1979)], and in isolated mitochondrial preparations from heart, soleus and gastrocnemius muscle and liver from treated animals NAD-linked respiration was reduced by 40% or more of mean control values. Brain and kidney mitochondria isolated from the treated group had similar rates of NAD-linked respiration to their respective control values. The activity of NADH-ferricyanide reductase was significantly reduced in all tissues tested, even in the isolated brain and kidney mitochondria where the activity in these tissues was 60-75% of control values. This suggests that at least 40% of Complex I activity must be inhibited before there is a decline in NAD-linked mitochondrial respiration. This paper discusses the use of diphenyleneiodonium as a means of establishing an animal model of the human disease state, termed mitochondrial myopathy.


Shared and specific dynamics of brain segregation and integration in bipolar disorder and major depressive disorder: A resting-state functional magnetic resonance imaging study.
When bipolar disorder (BD) presents as the depressive state, it is often misdiagnosed as major depressive disorder (MDD). However, few studies have focused on dynamic differences in local brain activity and connectivity between BD and MDD. Therefore, the present study explored shared and specific patterns of abnormal dynamic brain segregation and integration in BD and MDD patients. BD Patients (n = 106), MDD patients (n = 114), and 130 healthy controls (HCs) underwent resting state functional magnetic resonance imaging (fMRI). We first used a sliding window analysis to evaluate the dynamic amplitude of low-frequency fluctuations (dALFF) and, based on the altered dALFF, further analyzed the dynamic functional connectivity (dFC) using a seed-based approach. Both the BD and MDD groups showed decreased temporal variability of the dALFF (less dynamic segregation) in the bilateral posterior cingulate cortex (PCC)/precuneus compared with the HCs. The MDD group showed increased temporal variability of the dALFF (more dynamic segregation) in the left putamen compared with the controls, but there was no significant difference between the BD and HCs. The dFC analysis also showed that both the BD and MDD groups had reduced dFC (less dynamic integration) between the bilateral PCC/ precuneus and the left inferior parietal lobule compared with the HCs. This study was cross-sectional and did not examine data from remitted BD and MDD patients. Our findings indicated disrupted dynamic balance between segregation and integration within the default mode network in both BD and MDD. Moreover, we found MDD-specific abnormal brain dynamics in the putamen.


An AI model to estimate visual acuity based solely on cross-sectional OCT imaging of various diseases.
To develop an artificial intelligence (AI) model for estimating best-corrected visual acuity (BCVA) using horizontal and vertical optical coherence tomography (OCT) scans of various retinal diseases and examine factors associated with its accuracy. OCT images and associated BCVA measurements from 2,700 OCT images (accrued from 2004 to 2018 with an Atlantis, Triton; Topcon, Tokyo, Japan) of 756 eyes of 469 patients and their BCVA were retrospectively analysed. For each eye, one horizontal and one vertical OCT scan in cross-line mode were used. The GoogLeNet architecture was implemented. The coefficient of determination (R2), root mean square error (RMSE) and mean absolute error (MAE) were computed to evaluate the performance of the trained network. R2, RMSE, and MAE were 0.512, 0.350, and 0.321, respectively. R2 was higher in phakic eyes than in pseudophakic eyes. Multivariable regression analysis showed that a higher R2 was significantly associated with better BCVA (p < 0.001) and a higher standard deviation of BCVA (p < 0.001). However, the performance was worse in an external validation, with R2 of 0.19. R2 values for retinal vein occlusion and age-related macular degeneration were 0.961 and 0.373 in the internal validation but 0.20 and 0.22 in the external validation. Although underspecification appears to be a fundamental problem to be addressed in AI models for predicting visual acuity, the present results suggest that AI models might have potential for estimating BCVA from OCT in AMD and RVO. Further research is needed to improve the utility of BCVA estimation for these diseases.


Assessing the criterion validity of four highly abbreviated measures from the Minimal Assessment of Cognitive Function in Multiple Sclerosis (MACFIMS).
Cognitive dysfunction is prevalent in multiple sclerosis. As self-reported cognitive functioning is unreliable, brief objective screening measures are needed. Utilizing widely used full-length neuropsychological tests, this study aimed to establish the criterion validity of highly abbreviated versions of the Brief Visuospatial Memory Test - Revised (BVMT-R), Symbol Digit Modalities Test (SDMT), Delis-Kaplan Executive Function System (D-KEFS) Sorting Test, and Controlled Oral Word Association Test (COWAT) in order to begin developing an MS-specific screening battery. Participants from Holy Name Medical Center and the Kessler Foundation were administered one or more of these four measures. Using test-specific criterion to identify impairment at both -1.5 and -2.0 SD, receiver-operating-characteristic (ROC) analyses of BVMT-R Trial 1, Trial 2, and Trial 1 + 2 raw data (N = 286) were run to calculate the classification accuracy of the abbreviated version, as well as the sensitivity and specificity. The same methods were used for SDMT 30-s and 60-s (N = 321), D-KEFS Sorting Free Card Sort 1 (N = 120), and COWAT letters F and A (N = 298). Using these definitions of impairment, each analysis yielded high classification accuracy (89.3 to 94.3%). BVMT-R Trial 1, SDMT 30-s, D-KEFS Free Card Sort 1, and COWAT F possess good criterion validity in detecting impairment on their respective overall measure, capturing much of the same information as the full version. Along with the first two trials of the California Verbal Learning Test - Second Edition (CVLT-II), these five highly abbreviated measures may be used to develop a brief screening battery.


Psychosocial Interventions for Pain Management in Breast Cancer Survivors: A RE-AIM Evaluation.
Psychosocial interventions for breast-cancer-related pain are effective, yet over 45% of survivors continue to struggle with this often-chronic side effect. This study evaluated multilevel indicators that can influence successful translation of interventions into clinical practice. The Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework was applied to evaluate reporting of individual and setting/staff-level intervention indicators. A systematic search and multi-step screening process identified 31 randomized controlled trials for psychosocial interventions for breast cancer-related pain. Average reporting of indicators for individual-level dimensions (Reach and Effectiveness) were 65.2% and 62.3%, respectively. Comparatively, indicators for setting/staff-level dimensions were reported at a lower average frequency (Implementation, 46.8%; Adoption, 15.2%; Maintenance, 7.7%). Low reporting of setting/staff-level dimensions suggests gaps in the sustained implementation of psychosocial interventions. Implementation science methods and frameworks could improve trial design and accelerate the translation of psychosocial interventions for breast cancer-related pain into clinical practice.


[Neprhon sparing surgery for renal tumours on kidney transplantation].
Nowadays, nephron sparing surgery for renal carcinoma achieves good oncological results, similar to radical surgery, with the advantage of preserving renal function. Renal cell carcinomas appear de novo in 4.6% of post-transplant patients compared with 3% of tumors in the general population, affecting less than 10% to renal allograft. The purpose is to analyze our experience and make a literature review about the role of nephron sparing surgery to treat de novo renal tumours in renal grafts. A retrospective and descriptive analysis has been realized, finding four patients who presented with de novo renal tumours over renal graft after kidney transplantation and treated by nephron sparing surgery. A Medline review is done to search similar series published. Oncological and functional results were reviewed and analyzed. We worked with SPSS 12.0 software. Medium age at diagnosis was 46.5 y (42-62). Medium size was 2.4cm. (1.5-3.5) and final histology showed medium tumours size of 3.0cm. (1.7-3.5). Medium hospital stay was 6.0d. Medium time from transplantation to diagnosis was 92 months (42-192). NSS was done in all cases, in 3 cases tumorectomy and one partial nephrectomy. Transfusion was only needed in one case. All cases had pT1aN0M0 RCC histology exam. Renal function did not change from preoperative. All patients are free of progression with a medium follow-up of 46.5 months (15-58). NSS could be an option to treat graft tumours in selected cases, preserving renal function. In our experience, is a safe and efficient treatment in patients with small de novo renal tumours over renal graft.


The novel HLA-DRB1*12:02:11 allele identified by next-generation sequencing in a Chinese bone marrow donor.
HLA-DRB1*12:02:11 differs from HLA-DRB1*12:02:01:01 by a single nucleotide substitution at position 579 T > G.


Carcinoma ex pleomorphic adenoma of the sublingual gland: a case report.
We report a case of carcinoma ex pleomorphic adenoma of a sublingual gland in a 70-year-old man. Under a clinical diagnosis of benign salivary gland tumor, excision of the mass with the sublingual salivary gland in an en bloc fashion via an intraoral approach was performed. Histopathologically, there was a rupture of the fibrous capsule and diffuse cell-rich sheets composed of myoepithelial cells with round nuclei were also seen. Immunohistochemically, the cells that composed of cell rich sheets were positive to smooth muscle actin. Final diagnosis of myoepithelial carcinoma ex pleomorphic adenoma was made.


Dusky salamanders (Desmognathus, Plethodontidae) from the Coastal Plain: multiple independent lineages and their bearing on the molecular phylogeny of the genus.
Recent phylogenetic reassessment of the lungless salamanders (Plethodontidae) confirmed a major life-history reversal-from direct development to an aquatic larval stage-in the dusky salamanders (Desmognathus) of eastern North America. This reversal initiated high rates of lineage accumulation, reputedly generating the species richness and ecological breath that now characterize Desmognathus. Certain important aspects of the radiation, e.g., ecomorphological evolution, have been identified through intense sampling effort of Appalachian Highland lineages. However, the research preoccupation on montane species has left overlooked a significant component of dusky salamander distribution-the Coastal Plain. We present the first molecular phylogeny for Desmognathus to incorporate extensive coverage from the Atlantic and Gulf coastal plains. We examined 38 Coastal Plain populations in conjunction with 45 additional populations, representing 16 of the 19 nominal species. Bayesian analysis of 88 mitochondrial cox1 haplotypes diagnosed eight independent population lineages within the Coastal Plain, a number at odds with the region's three currently recognized species. Desmognathus has apparently experienced a complex biogeographic history in this physiographic region, one involving multiple invasions and several ecological transitions from lotic to lentic habitats.


Evaluation of recA sequencing for the classification of Aeromonas strains at the genotype level.
To evaluate the usefulness of partial recA sequences for the identification of Aeromonas strains at the genotype level. A partial recA sequence was obtained from 21 type or reference strains and 33 Aeromonas isolates, collected in the South of Switzerland from human, animal and aquatic environments. The 272 bp long recA fragments showed a mean interspecies divergence of 7.8% and allowed the classification of strains at genotype level. However, some discrepancies could be observed with other gene sequence based analyses in the classification of some strains. The 272 bp long recA fragment is a good molecular marker to infer taxonomy of members of the genus Aeromonas, even if the primers we chose for the amplification did not allow its direct sequencing. In the genus Aeromonas, nucleotide sequences of some protein-encoding genes have already been evaluated as molecular markers to be used in taxonomical and epidemiological researches. This study suggests the usefulness of a recA fragment as a further sequence to investigate for these purposes.


A critical review of the available evidence on the diagnosis and clinical features of CPPD: do we really need imaging?
Imaging has been playing an important role in the pathogenetic and clinical characterisation of many rheumatic diseases, especially in the most recent years with the advent of many new, highly technological and promising techniques. Calcium pyrophosphate deposition disease (CPPD) benefited also from these new techniques, most of which can readily identify calcium crystals. Nowadays, imaging is used mainly to identify crystals in joints but given the complexity of CPPD, imaging should be used with an "holistic" approach in order to gain insights in the pathogenesis, spectrum of clinical manifestations and natural history of the disease. Furthermore, overlap or association of CPPD with other prevalent diseases of the elderly makes the differential diagnosis challenging. In this review, we provide a critical review of the current knowledge on the use of imaging both for the identification of crystals and for its application in clinical practice as an aid for determining the impact of the disease on patients.Key Points• CPPD is a complex disease with a wide spectrum of clinical manifestations and understanding of pathogenetic mechanisms and clinical phenotypes is essential for correct characterisation• Imaging has made important advances regarding identification of CPPD in recent years, and new, more sophisticated techniques are under investigation• Imaging has the potential to improve our knowledge on pathogenesis and clinical phenotypes of CPPD• Imaging techniques have to be tested thoroughly for reliability, discrimination and sensitivity to change before they can be implemented in clinical trials.


Neurocysticercosis presented as a solitary cystic parenchymal lesion mimicking primary brain tumor: A case report.
Neurocysticercosis (NCC) is an infection of the central nervous system by the larval stage of pork tapeworm (Taenia solium/T. solium). Diagnosing NCC can be challenging, particularly among those who reside in areas with rare occurrence of NCC and atypical manifestation such as a solitary parenchymal lesion. We treated a patient whose initially was diagnosed with brain abcess and later, brain tumor, only finally revealed to be an NCC case. A 25-year old male suffered from multiple focal-to-bilateral tonic clonic seizures, was initially diagnosed as brain abscess. He was given antibiotics and anti-seizure medication but the seizure relapsed with a typical semiology. Physical examination demonstrated grade I papilledema, grade 4+ hemiparesis, and headache of vascular origin. Patient was suspected to have oligodendroglioma after underwent head MRI examination and subsequent tumor resection was performed. Pathological anatomy evaluation demonstrated multiple cystic segments containing larva of tapeworm, supporting a diagnosis of active NCC infection. After 14-day course of antheminthic treatment and resumed AED, patient was seizure-free and NCC was not found upon follow-up CT scan. NCC, with respect to clinical and radiological manifestations, can be protean. A high index of suspicion towards NCC should always be maintained, particularly among patients originated from endemic area. Appropriate treatment with anthelminthic may result in full disease resolution, thus precluding unnecessary invasive approach.


Retromuscular mesh and hernial sac technique in the reconstruction of 139 cases of large median incisional hernias: one institution's experience.
Incisional hernia is the most common complication of laparotomy. Postoperative parietal defects tend to relapse, even after the most optimal surgical methods. The aim of this study was to present the effectiveness of an adapted retromuscular technique with prolene mesh and a hernial sac, in patients with large incisional median hernias. The reported results were obtained by our team after more than 15 years of experience. This retrospective study included 139 consecutive cases of large median incisional hernias operated on using a retromuscular mesh and hernial sac technique. The cross-sectional diameter of incisional hernias was larger than 10 cm, being classified in the W3 group, according to the European Hernia Society classification. The study included 83 females (59.71%) and 56 males (40.29%) with a median age of 62.4 ± 16.6 years and an average body mass index of 32.4 ± 7.6 kg. The hernia was supraumbilically located in 54 cases, subumbilically in 61 cases, and supra- and subumbilically in 24 cases. Postoperative complications were recorded in eight cases (5.75%): one case with a hematoma in the right abdominal muscle sheath; five cases with supra-aponeurotic seromas; two cases with skin necrosis and one with a mesh infection. Recurrence occurred in seven cases (5.03%): four cases in the first 2 years postoperatively and three cases in the third year after surgery. The retromuscular technique with prolene mesh and a hernial sac is an effective method of restoring the integrity of the abdominal wall in large median incisional hernias with low rates of morbidity and recurrence.


Evolution of focal choroidal excavation in ABCA4-related retinopathy.
To report long-term evolution of unilateral focal choroidal excavation in a patient with ABCA4-related retinopathy. A 51-year-old female with ABCA4-related retinopathy developed a small juxtafoveal defect in Bruch's membrane in a region of macular atrophy in her left eye. In follow-up, the defect widened and subsequently developed into a focal choroidal excavation. Over the next 8 years, serial optical coherence tomography imaging illustrated the conversion of the focal choroidal excavation from conforming subtype into non-conforming subtype with eventual macular hole formation. The long-term follow-up of a patient with serial imaging highlights the potential dynamic nature of focal choroidal excavation in ABCA4-related retinopathy. Progressive retinal degeneration may influence focal choroidal excavation morphology and may promote macular hole formation.


Sex differences in thickness, and folding developments throughout the cortex.
While significant differences in male and female brain structures have commonly been reported, only a few studies have focused on the sex differences in the way the cortex matures over time. Here, we investigated cortical thickness maturation between the age of 6 to 30 years, using 209 longitudinally-acquired brain MRI scans. Significant sex differences in the trajectories of cortical thickness change with age were evidenced using non-linear mixed effects models. Similar statistical analyses were computed to quantify the differences between cortical gyrification changes with age in males and females. During adolescence, we observed a statistically significant higher rate of cortical thinning in females compared to males in the right temporal regions, the left temporoparietal junction and the left orbitofrontal cortex. This finding is interpreted as a faster maturation of the social brain areas in females. Concomitantly, statistically significant sex differences in cortical folding changes with age were observed only in one cluster of the right prefrontal regions, suggesting that the mechanisms underlying cortical thickness and gyrification changes with age are quite distinct. Sexual dimorphism in the developmental course of the cortical maturation may be associated with the different age of onset and clinical presentation of many psychiatric disorders between males and females.


Conventional antithrombotic approaches.
Thrombus formation during percutaneous transluminal coronary angioplasty (PTCA) markedly increases the risk of abrupt closure, procedural failure, and major complications. Pretreatment with heparin may be beneficial in preventing procedural complications, although strategies for ensuring that patients have adequate anticoagulation have been the focus of considerable debate. Several studies have suggested a relationship between the development of PTCA complications and a low activated clotting time (ACT) or a low increase in ACT in response to heparin. Although there have been no prospective studies showing the superiority of any given threshold ACT over any other, current data support a recommendation that anticoagulation for patients undergoing PTCA be titrated to a HemoTec ACT of greater than 275 to 300 seconds or to a Hemochron ACT of greater than 350 to 400 seconds. Adjusting the heparin bolus dose according to body weight does not achieve a more predictable level of anticoagulation, although it may help avoid excessive anticoagulation in lighter-weight patients.


Effectiveness and safety of sodium-glucose co-transporter-2 inhibitors compared with dipeptidyl peptidase-4 inhibitors in older adults with type 2 diabetes: A nationwide population-based study.
To examine the real-world cardiovascular effectiveness and safety associated with sodium-glucose co-transporter-2 (SGLT2) inhibitor compared with dipeptidyl peptidase-4 (DPP-4) inhibitor treatment in older adults with type 2 diabetes. In this retrospective cohort study, older adults with type 2 diabetes (aged ≥65 years) were identified in the Korean National Health Insurance Service database from September 2014 to December 2016. In total, 408 506 new users of an SGLT2 inhibitor or DPP-4 inhibitor were propensity score matched. Cox regression was used to estimate the hazard ratios (HR) and 95% confidence interval (CI) for outcomes of interest: hospitalization for heart failure (HHF), all-cause death, myocardial infarction, stroke, diabetic ketoacidosis (DKA), bone fracture, severe hypoglycaemia, genital infection and urinary tract infection (UTI). Compared with DPP-4 inhibitors, new users of SGLT2 inhibitors had a lower risk of HHF (HR 0.86; 95% CI 0.76-0.97), all-cause death (HR 0.85; 95% CI 0.75-0.98) and stroke (HR 0.86; 95% CI 0.77-0.97), but a similar risk of myocardial infarction (HR 0.95; 95% CI 0.77-1.19). The risks of DKA, bone fracture and severe hypoglycaemia were similar between both groups, although genital infection (HR 2.44; 95% CI 2.22-2.67) and UTI (HR 1.05; 95% CI 1.00-21.11) were more frequent among new users of SGLT2 inhibitors compared with DPP-4 inhibitors. Our findings suggest that initiation of SGLT2 inhibitors offers cardiovascular disease protection and can be used safely in older adults with type 2 diabetes.


A randomized placebo-controlled double-blind study of dexmedetomidine on postoperative sleep quality in patients with endoscopic sinus surgery.
Postoperative sleep disorder is common and may cause aggravated postoperative pain, delirium, and poor prognosis. We accessed the effect of intraoperative intravenous dexmedetomidine on postoperative sleep quality in patients with endoscopic sinus surgery. METHODS: This single-center, double-blind, placebo-controlled randomized clinical trial enrolled a total of 110 participants aged 18 years to 65 years who were scheduled to receive endoscopic sinus surgery. Placebo (normal saline) or dexmedetomidine infusion (load dose 0.5 μg kg-1 over 10 min, followed by maintenance dose 0.2 ug kg-1 h-1) during surgery. The primary outcome was postoperative sleep quality. Secondary outcomes were postoperative Ramsay sedation scores, Visual Analog Scale (VAS) scores, serum cortisol, 5-hydroxytryptamine (5-HT) and hypocretin, delirium, and postoperative nausea and vomiting (PONV). Among enrolled 110 patients, 55 were randomized to administer intraoperative dexmedetomidine and placebo. In total, 14 patients (7 in each group) were excluded because of protocol deviations, and 96 patients (48 in each group) were included in the per-protocol analysis. The dexmedetomidine group had a significantly higher sleep efficiency index(SEI) (66.85[3.00] vs 65.38[3.58]), the ratio of rapid eye movement sleep to total sleep(REM)(13.63[1.45] vs 12.38[2.11]) and lower arousal index (AI) (7.20[1.00] vs 8.07[1.29]), higher Ramsay sedation score at post-operation 1 h, 12 h point, lower VAS scores at post-operation 1 h, 12 h, 24 h point, lower cortisol, higher 5-HT and hypocretin in serum than the placebo group. In this randomized clinical trial, dexmedetomidine can improve the sleep quality of patients undergoing endoscopic sinus surgery. These results suggest that this therapy may be a viable strategy to enhance postoperative sleep quality in patients with endoscopic sinus surgery. The study was approved by the Bethune International Peace Hospital Ethics Committee (2021-KY-129) and registered in the Chinese Clinical Trial Registry ( ChiCTR2100051598 , 28/09/2021).