Impact of maternal zinc status on fetal growth in an Iranian pregnant population.
To evaluate the impact of mild to moderate maternal zinc deficiency on birth weight of offsprings in a group of Iranian pregnant population. One hundred forty pregnant subjects with no history of medical complications during pregnancy and without any inter-current illness enrolled in the study. Serum zinc concentration, ferritin, hemoglobin, iron, and total iron binding capacity (TIBC) were measured at the time of delivery. The receiver operator characteristic (ROC) curve analysis used to determine plasma zinc cutoff value for comparison. Of 140 live neonates, 30% were below 2500 g. Mean serum zinc concentration was 56.60 ± 17.91 μg/dl which indicated mild to moderate zinc deficiency. None of the subjects were anemic. There was an inverse statistically significant relationship between maternal serum zinc concentration and neonatal birth weight. In this group of Iranian pregnant subjects with mild to moderate zinc deficiency, we observed no relationship between low maternal zinc status and low birth weight infants.


Impact of optional multidisciplinary tumor board meeting on the mortality of patients with gastrointestinal cancer: A retrospective observational study.
Multidisciplinary tumor board meetings (MDTs) have shown a positive effect on patient care and play a role in the planning of care. However, there is limited evidence of the association between MDTs and patient mortality and in-hospital morbidity for mixed cases of gastrointestinal (GI) cancer. To evaluate the influence of optional MDTs on care of patients with cancer to determine potential associations between MDTs and patient mortality and morbidity. This was a retrospective observational study at the referral center of King Abdulaziz University Hospital, Jeddah, Kingdom of Saudi Arabia. Among all adult patients diagnosed with GI cancer from January 2017 to June 2019, 130 patients were included. We categorized patients into two groups: 66 in the control group (non-MDT) and 64 in the MDT group. The main outcome measure was overall mortality, measured by survival analysis. The follow-up was 100% complete. Four patients in the MDT group and 13 in the non-MDT group died (P = .04). The median follow-up duration was 294 days (interquartile range [IQR], 140-434) in the non-MDT group compared with 176 days (IQR, 103-466) in the MDT group (P = .20). There were no differences in intensive care unit or hospital length-of-stay or admission rates. The overall mortality at 2 years was 13% (95% confidence interval [CI], 0.06-0.66) in the MDT group and 38% (95% CI, 0.10-0.39) in the non-MDT group (P = .08). The MDT group showed a 72% (adjusted hazard ratio [HR], 0.28; 95% CI, 0.08-0.90; P = .03) decrease in mortality over time compared with the non-MDT group. MDTs were associated with decreased mortality over time. Thus, MDTs have a positive influence on patient care by improving survival and should be incorporated into care.


Catechol O-methyltransferase (COMT) mRNA expression in the dorsolateral prefrontal cortex of patients with schizophrenia.
Human prefrontal cortical neurons express catechol O-methyltransferase (COMT), an enzyme that inactivates the neurotransmitter dopamine. A functional polymorphism of COMT, Val(108/158) Met, affects prefrontal function, and the high-activity Val allele has been reported to be a genetic risk factor for schizophrenia. We used in situ hybridization histochemistry to measure mRNA levels of COMT in the dorsolateral prefrontal cortex (DLPFC) of patients with schizophrenia (N=14) and of normal controls (N=15). While the groups did not differ in terms of mean level of COMT mRNA, there was a significantly different laminar pattern of COMT mRNA expression in pyramidal neurons (F=2.68, df=4,108, P <0.04); patients with schizophrenia had relatively lower levels in the superficial (II/III) layers and higher levels in the intermediate/deep (IV/V) layers (P&<0.01), while in controls, the expression was homogeneous across layers. Neither the mean level nor the laminar distribution of COMT mRNA was related to the Val(108/158) Met genotype, suggesting that the feedback regulation of mRNA level is not a compensation for the functional effect of the COMT polymorphism. The disease-related laminar difference of COMT expression may be involved in dysregulation of dopamine signaling circuits in the DLPFC of patients with schizophrenia.


[Radiotherapy of lymphomas. Clinical classification, radiotherapy planning and indications].
The staging of Hodgkin's disease and non-Hodgkin lymphomas is discussed with reference to the treatment plan indicated for each stage and the problems associated with radiotherapy.


The microanatomy of the Sylvian fissure.
Microsurgical anatomy of the Sylvian fissure is still a popular research topic for neurosurgeons. It is important for surgeons who perform skull base and Sylvian fissure surgical procedures to master the anatomy of the region. In our study, we aimed to review the current literature on the subject. We reviewed the literature concerning the Sylvian fissure. In addition, we made a microdissection of four human cadaveric brains in order to take images of relevant anatomic structures. The Sylvian fissure includes both superficial and deep compartments. From the beginning of the surface structures and variable thickened subarachnoid membrane to the vascular structures located at the operculo-insular compartment, the surgical technique requires meticulous dissection in all stages of the surgery. From the view of neurosurgery, novel anatomical knowledge should enhance the success of the surgery. From the view of neuroscience, the Sylvian fissure and the Sylvian cistern have unique anatomical, vascular, and genotypical properties to the other areas of the cerebrum, making them complex and special.


Fast detection of methyl tert-butyl ether from water using solid phase microextraction and ion mobility spectrometry.
Methyl tert-butyl ether (MTBE) is commonly used as chemical additive to increase oxygen content and octane rating of reformulated gasoline. Despite its impact on enhancing cleaner combustion of gasoline, MTBE poses a threat to surface and ground water when gasoline is released into the environment. Methods for onsite analysis of MTBE in water samples are also needed. A less common technique for MTBE detection from water is ion mobility spectrometry (IMS). We describe a method for fast sampling and screening of MTBE from water by solid phase microextraction (SPME) and IMS. MTBE is adsorbed from the head space of a sample to the coating of SPME fiber. The interface containing a heated sample chamber, which couples SPME and IMS, was constructed and the SPME fiber was introduced into the sample chamber for thermal desorption and IMS detection of MTBE vapors. The demonstrated SPME-IMS method proved to be a straightforward method for the detection of trace quantities of MTBE from waters including surface and ground water. We determined the relative standard deviation of 8.3% and detection limit of 5 mg L(-1) for MTBE. Because of short sampling, desorption, and detection times, the described configuration of combined SPME and IMS is a feasible method for the detection of hazardous substances from environmental matrices.


Massive Orbital Infiltration and Trigeminal Enlargement in Churg-Strauss Syndrome Associated With IgG4 Plasma Cell Positivity.
The association of C-antineutrophil cytoplasmic antibody (ANCA) vasculitis and IgG4 positivity is a new condition not well described in clinical terms. The authors examined a 28-year-old man with a previous diagnosis of eosinophilic granulomatosis with polyangiitis, formerly known as Churg-Strauss disease, who presented with bilateral orbital inflammation. Magnetic resonance imaging revealed diffuse orbital infiltration and enlargement of the major divisions of the trigeminal nerve. Biopsy of the orbital contents showed necrotizing granulomatous vasculitis and a high number of IgG4-positive plasma cells (IgG4/IgG = 60%).


[THE CHOICE OF SURGICAL TREATMENT OF OBSTRUCTIVE ILEUS IN ELDERLY AND SENILE PATIENTS].
The article presents results of treatment of 100 patients with elderly colon cancer complicated by obstructive ileus. Patients were divided into two groups of 50 people. Main group patients for colon surgery performed using laparoscopic techniques. The efficiency of operations on the colon laparoscopically - fewer postoperative complications, length of postoperative hospital stay days. Deaths in the study group was not (control - 6 %).


Carbofuran degradation by the application of MW-assisted H₂O₂ process.
Carbofuran removal performance of a microwave (MW)-assisted H₂O₂ system under different MW-power levels (300-900 W) was investigated. Batch experiments were conducted at 100 mg/L carbofuran concentration using a modified-MW reactor with 2450 MHz of fixed frequency. As a precursor, control experiments were carried out with H₂O₂ alone, MW alone and conventional heating (CH). A maximum carbofuran removal of 14 % was observed in both H₂O₂ alone and CH systems. On the other hand, only 2 % removal was observed in the MW alone system irrespective of the operation-mode, i.e. continuous or pulsed. The combination of MW and H₂O₂ produced 100 % carbofuran removal in all the MW-assisted experiments. The MW-assisted system operated under continuous-mode and at 750 W has showed rapid carbofuran degradation, i.e. 30 sec, with the highest first-order removal rate constant of 25.82/min. However, 97 % carbon oxygen demand (COD) removal was observed in the same system only after 30 min. On the other hand, 100 % carbofuran removal and 49 % COD removal were observed in the pulsed-mode MW-assisted H₂O₂ system after 10 and 30 min, respectively. Carbofuran mineralization in the system was evidenced by the formation of ammonium and nitrate, and carbofuran intermediates.


Serum polybrominated diphenyl ether exposure and influence factors in blood donors of Wuxi adults from 2013 to 2016.
Polybrominated diphenyl ethers (PBDEs) have been used as brominated flame retardants worldwide and are correlated with extensive environmental pollution and human health concerns. This study is aimed at analyzing the concentrations of PBDEs and at evaluating their temporal trends among a population of blood donors (n = 33) over a 4-year period. A total of 132 serum samples were used for PBDE detection. Nine PBDE congeners were quantified in serum samples by gas chromatography with mass spectrometry (GC-MS). The median concentrations of Σ9PBDEs in each year were 33.46, 29.75, 30.85, and 35.02 ng/g lipid, respectively. Most of the PBDE congeners showed a downward trend from 2013 to 2014 and then increased after 2014. No correlations between age and PBDE congener concentrations were observed, while concentrations of each congener and Σ9PBDE were nearly always lower in females than in males, especially in BDE-66, BDE-153, BDE-183, BDE-190, and Σ9PBDE. We also found that the intake of fish, fruit, and eggs in the daily diet was related to the exposure level of PBDEs. Our results suggest that, as deca-BDE is still produced and used in China, diet is an important exposure pathway for PBDEs, and follow-up studies will be required to improve our understanding of the behaviors of PBDE isomers in humans and the exposure levels.


Cytokines Involved in COVID-19 Patients with Diabetes: A Systematic Review.
Hyperglycemic condition and compromised immune system may contribute to the progression of COVID-19 infection and increase the disease severity, relatively requiring a longer recovery period among diabetic patients. A systematic review was conducted to examine cytokine levels, the prevalence of risk factors, and other comorbidities in COVID-19 patients with and without diabetes mellitus during the early COVID-19 outbreak. A systematic literature search was conducted in PubMed central, PMC Europe databases, and Web of Science, evaluating the articles published between Dec 1st, 2019, and June 15th, 2020. This systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The systematic search generated 14,960 articles and ended up with 9 articles, of which 8 articles involved data on the comparison of cytokines in diabetic and non-diabetic subjects with COVID-19, while 4 of them involved data on cytokines in the diabetes patients compared either by the severity of diseases or the rate of survival. Among the studied cytokines, interleukin-6, interleukin- 8, and tumor necrosis factor-α may cause the worst prognosis or fatality among diabetic patients. Increased cytokine levels indicate higher mortality and are linked to risk factors and comorbidities, such as hypertension and cardiovascular disease. Management of diabetes by insulin treatment may reduce the rate of mortality among diabetic patients but may be contraindicated in diabetic patients with COVID-19 who had at least one previous comorbidity, especially hypertension and CVD. The pathophysiological mechanisms linked to cytokine storm in diabetic patients may lead to the design of treatment strategies in the future, thus improving early diagnosis of the disease and mitigating cytokine storm-associated morbidity and mortality.


Adenine nucleotides regulate Ca2+ transport in brain mitochondria.
Adenine nucleotides (ADP greater than ATP) greatly enhance Ca2+ uptake and retention in rat brain mitochondria. In the presence of both spermine and ADP, brain mitochondria sequester Ca2+ down to cellular free Ca2+ levels, suggesting a role for mitochondria in modulating Ca2+ cycles in brain cells. Analysis of the effects of various inhibitors on Ca2+ uptake and efflux suggest that locking the ADP/ATP translocator in its M-state stimulates electrogenic Ca2+ uptake and, to a lesser extent, inhibits Ca2+ efflux. It is suggested that this effect is due to a modulation of the surface charge on the M-side which enhances Ca2+ dissociation from the carriers.


Protecting self-esteem from stigma: a test of different strategies for coping with the stigma of mental illness.
To date, there has been little research into effective strategies for preventing the detrimental effects of stigma on the well-being of people with mental illness. The present research set out to identify adaptive strategies for dealing with the stigma of mental illness. On the basis of the responses of 355 people with mental illness (PWMI) a standardized questionnaire assessing 10 identity management strategies was developed. Participants also reported their personal experiences with stigma, depression and self-esteem. Hierarchical regression analyses showed that after controlling for depression and stigmatizing experiences, the strategies of community involvement, humour and positive ingroup stereotyping were related to higher self-esteem. Secrecy, selective disclosure and attempts at overcompensation or disproving stereotypes were related to lower self-esteem. The following strategies were unrelated to self-esteem: comparing the present social position of PWMI with that in the past, normalization of the illness within a medical model, information seeking and selective withdrawal. PWMI should be encouraged to seek support within their community and to develop a positive image of their ingroup.


Ice chromatography modification of solute retention on water-ice stationary phase.
Ice chromatography, in which water-ice particles are used as the stationary phase, has high potential as a separation tool, and is an efficient approach to probe the molecular interaction occurring on the water-ice surface. In the present paper, to modify solute retention, several methods are proposed, that is, changing the mobile phase composition, the surface modification of water-ice, and the implantation of functional molecules into water-ice. The retention mechanism of ice chromatography is discussed through these retention modifications.


Phylogenomics reveals the basis of adaptation of Pseudorhizobium species to extreme environments and supports a taxonomic revision of the genus.
The family Rhizobiaceae includes many genera of soil bacteria, often isolated for their association with plants. Herein, we investigate the genomic diversity of a group of Rhizobium species and unclassified strains isolated from atypical environments, including seawater, rock matrix or polluted soil. Based on whole-genome similarity and core genome phylogeny, we show that this group corresponds to the genus Pseudorhizobium. We thus reclassify Rhizobium halotolerans, R. marinum, R. flavum and R. endolithicum as P. halotolerans sp. nov., P. marinum comb. nov., P. flavum comb. nov. and P. endolithicum comb. nov., respectively, and show that P. pelagicum is a synonym of P. marinum. We also delineate a new chemolithoautotroph species, P. banfieldiae sp. nov., whose type strain is NT-26T (=DSM 106348T=CFBP 8663T). This genome-based classification was supported by a chemotaxonomic comparison, with increasing taxonomic resolution provided by fatty acid, protein and metabolic profiles. In addition, we used a phylogenetic approach to infer scenarios of duplication, horizontal transfer and loss for all genes in the Pseudorhizobium pangenome. We thus identify the key functions associated with the diversification of each species and higher clades, shedding light on the mechanisms of adaptation to their respective ecological niches. Respiratory proteins acquired at the origin of Pseudorhizobium were combined with clade-specific genes to enable different strategies for detoxification and nutrition in harsh, nutrient-poor environments.


Side effects of BNT162b2 mRNA COVID-19 vaccine: A randomized, cross-sectional study with detailed self-reported symptoms from healthcare workers.
Concerns are prevailing about the safety and side effects of the BNT162b2 mRNA vaccine for coronavirus disease 2019 (COVID-19). A randomized, cross-sectional study was performed to investigate the side effects of the BNT162b2 vaccine using an independent online questionnaire gathering responses from healthcare workers (HCWs) with detailed review of organ systems. Of all HCWs, 87.98% (1245/1415) completed the survey. Of them, 64.5% (803/1245) received the BNT162b2 mRNA vaccine and reported at least one or more symptoms (classified based on organ systems and occurrence rate) post vaccination. Of these, 640/803 (79.7%) were able to continue activities of daily living (ADL), 103/803 (12.83%) had trouble temporarily to perform ADL, 99/803 (12.33%) took time off work temporarily, 20/803 (2.49%) required help from an outpatient provider, 5/803 (0.62%) required help from an emergency department and 2/803 (0.25%) required hospitalization. Despite this, 97.61% intended to have the second dose and 92.9% had already received it. Commonly reported symptoms (occurrence in descending order) were soreness, fatigue, myalgia, headache, chills, fever, joint pain, nausea, muscle spasm, sweating, dizziness, flushing, feelings of relief, brain fogging, anorexia, localized swelling, decreased sleep quality, itching, tingling, diarrhoea, nasal stuffiness and palpitations. Despite this, remarkable acceptance for the second dose of the BNT162b2 vaccine was found among HCWs.


Effect of buffer systems and pHi on the measurement of [Ca2+]i with fura 2.
The fluorescent probe, fura 2, is widely used to measure agonist-induced changes in intracellular calcium concentration ([Ca2+]i) in cultured cells. However, in many instances, the results obtained in the same cell type have differed from one study to the next. The possibility that such differences might be due to experimental conditions was examined by using fura 2 in four different cell types responding to appropriate agonists when the cells were incubated in either CO2/HCO3-- or HEPES-buffered media. Examined were: 1) the response of rat glomerular mesangial cells to arginine vasopressin, 2) the response of vascular smooth muscle cells to angiotensin II, 3) the response of adrenal glomerulosa cells to angiotensin II, and 4) the response of hypothalamic cells to insulin-like growth factor-1. In each cell type there was a significant difference in the pattern of agonist-induced change in [Ca2+]i when HEPES vs. CO2/HCO3- was used as the buffer system: in HEPES buffer, agonist addition led to a transient rise in [Ca2+]i followed by a fall to a sustained plateau 27 to 34 nM higher than the original basal value, whereas in CO2/HCO3- buffer, agonist addition led to an identical transient increase in [Ca2+]i followed by a fall to a value within 10 nM or less of the preagonist level. The plateau value of [Ca2+]i in the different buffers was examined in relationship to known differences in intracellular pH (pHi). It was found that measurements of [Ca2+]i with fura 2 were influenced by shifts in pHi that occur when cells are incubated in either HEPES-buffered or CO2/HCO3- media of differing pHo values. However, at any given value of pHi, the apparent [Ca2+]i measured in cells incubated in HEPES-buffered media was slightly higher than in cells incubated in CO2/HCO3- buffered media.


Can drugs improve memory?
Drug-induced manipulation of the cholinergic system may possibly be able to reverse memory deficits due to old age.


Epidemiology of Acute Kidney Injury After Neonatal Cardiac Surgery: A Report From the Multicenter Neonatal and Pediatric Heart and Renal Outcomes Network.
Cardiac surgery-associated acute kidney injury occurs commonly following congenital heart surgery and is associated with adverse outcomes. This study represents the first multicenter study of neonatal cardiac surgery-associated acute kidney injury. We aimed to describe the epidemiology, including perioperative predictors and associated outcomes of this important complication. This Neonatal and Pediatric Heart and Renal Outcomes Network study is a multicenter, retrospective cohort study of consecutive neonates less than 30 days. Neonatal modification of The Kidney Disease Improving Global Outcomes criteria was used. Associations between cardiac surgery-associated acute kidney injury stage and outcomes (mortality, length of stay, and duration of mechanical ventilation) were assessed through multivariable regression. Twenty-two hospitals participating in Pediatric Cardiac Critical Care Consortium. Twenty-two-thousand forty neonates who underwent major cardiac surgery from September 2015 to January 2018. None. Cardiac surgery-associated acute kidney injury occurred in 1,207 patients (53.8%); 983 of 1,657 in cardiopulmonary bypass patients (59.3%) and 224 of 583 in noncardiopulmonary bypass patients (38.4%). Seven-hundred two (31.3%) had maximum stage 1, 302 (13.5%) stage 2, 203 (9.1%) stage 3; prevalence of cardiac surgery-associated acute kidney injury peaked on postoperative day 1. Cardiac surgery-associated acute kidney injury rates varied greatly (27-86%) across institutions. Preoperative enteral feeding (odds ratio = 0.68; 0.52-0.9) and open sternum (odds ratio = 0.76; 0.61-0.96) were associated with less cardiac surgery-associated acute kidney injury; cardiopulmonary bypass was associated with increased cardiac surgery-associated acute kidney injury (odds ratio = 1.53; 1.01-2.32). Duration of cardiopulmonary bypass was not associated with cardiac surgery-associated acute kidney injury in the cardiopulmonary bypass cohort. Stage 3 cardiac surgery-associated acute kidney injury was independently associated with hospital mortality (odds ratio = 2.44; 1.3-4.61). No cardiac surgery-associated acute kidney injury stage was associated with duration of mechanical ventilation or length of stay. Cardiac surgery-associated acute kidney injury occurs frequently after neonatal cardiac surgery in both cardiopulmonary bypass and noncardiopulmonary bypass patients. Rates vary significantly across hospitals. Only stage 3 cardiac surgery-associated acute kidney injury is associated with mortality. Cardiac surgery-associated acute kidney injury was not associated with any other outcomes. Kidney Disease Improving Global Outcomes criteria may not precisely define a clinically meaningful renal injury phenotype in this population.


Spectral characterization and impact of stepwise ablation protocol including LAA electrical isolation on persistent AF.
To study how left atrial appendage electrical isolation (LAAEI) impacts atrial dominant frequency (DF) in patients with long-standing persistent atrial fibrillation (LSPAF). LAAEI is associated with a high probability of freedom from atrial fibrillation (AF) and spectral analysis may identify high-frequency sources. How LAAEI impacts the AF dynamics and the subgroup of LSPAF patients in whom LAAEI would be most beneficial, is unclear. Twenty patients with LSPAF were included in the study. Fast Fourier transforms (FFT) were performed on atrial electrograms recorded from 13 sites in the LA and RA. The highest peak frequency was defined as DF. There was no significant difference in DF between atrial sites except for at the superior vena cava which had the lowest DF at baseline. Stepwise ablation consisting of circumferential pulmonary vein isolation and a linear ablation set of mitral isthmus and roof significantly reduced the DF within the coronary sinus (CS) (5.93 ± 0.98 Hz vs. 5.09 ± 0.72 Hz, p < .05) and the LA posterior wall (LApos) (6.26 ± 0.92 Hz vs. 5.43 ± 0.98 Hz, p < .01). LAAEI preferentially further decreased the DF at the LApos (p < .01), but not at the CS. In cases where there was < 13.6% reduction in the DF of the LApos following the stepwise ablation, the addition of LAAEI was associated with an increased restoration of sinus rhythm (55%, p < .05). LAAEI in addition to stepwise ablation results in further reduction of the DF in the LApos, which is associated with acute termination of AF and favorable ablation outcome.


A high-fat diet and NAD(+) activate Sirt1 to rescue premature aging in cockayne syndrome.
Cockayne syndrome (CS) is an accelerated aging disorder characterized by progressive neurodegeneration caused by mutations in genes encoding the DNA repair proteins CS group A or B (CSA or CSB). Since dietary interventions can alter neurodegenerative processes, Csb(m/m) mice were given a high-fat, caloric-restricted, or resveratrol-supplemented diet. High-fat feeding rescued the metabolic, transcriptomic, and behavioral phenotypes of Csb(m/m) mice. Furthermore, premature aging in CS mice, nematodes, and human cells results from aberrant PARP activation due to deficient DNA repair leading to decreased SIRT1 activity and mitochondrial dysfunction. Notably, β-hydroxybutyrate levels are increased by the high-fat diet, and β-hydroxybutyrate, PARP inhibition, or NAD(+) supplementation can activate SIRT1 and rescue CS-associated phenotypes. Mechanistically, CSB can displace activated PARP1 from damaged DNA to limit its activity. This study connects two emerging longevity metabolites, β-hydroxybutyrate and NAD(+), through the deacetylase SIRT1 and suggests possible interventions for CS.


Estimating the size of a potential palliative care population.
To develop a method for estimating the population who could potentially benefit from receiving palliative care in the last year of their lives, and then apply the estimates to the Western Australian population to ascertain characteristics of these people. Three estimates of the potential palliative care population, Minimal, Mid-range and Maximal, were developed through focus groups, interviews and the literature. These estimates were applied to the cohort of people who died in Western Australia between 1 July 2000 and 31 December 2002 by linking death records with hospital morbidity data through the Western Australian Data Linkage System. Between 0.28% and 0.50% of people in the Western Australian population in any one year could potentially benefit from palliative care, many of whom die from conditions other than neoplasms. While neoplasms accounted for 59.5% of all underlying causes of deaths in the Minimal Estimate, heart failure (21.0%), renal failure (9.8%), chronic obstructive pulmonary disease (9.6%), Alzheimer's disease (4.0%), liver failure (3.2%), Parkinson's disease (1.3%), motor neurone disease (0.9%), HIV/AIDS (<0.01%) and Huntington's disease (<0.01%) accounted for other conditions in this estimate. The study was expanded to include Mid-range and Maximal Estimates. Characteristics of the Western Australian population in these three estimates are described. Unlike traditional palliative care estimates that focus on malignant disease, this study included nonmalignant conditions in a set of three estimates of a potential palliative care population. By using population-based data to describe characteristics of people who compose palliative care populations, these results offer a tool for planning equitable healthcare services.


Selective fluorescence sensing of Li+ in an aqueous environment by a ferrocene-anthracene-linked dyad.
A new 1-(9-anthryl)-4-ferrocenyl-2-aza-1,3-butadiene showing selective fluorescence enhancement upon binding to lithium cations over other alkaline cations in aqueous environment has been conveniently synthesized and characterized. [structure: see text]


Probing the determinants of phosphorylated sugar-substrate binding for human sialic acid synthase.
N-acetylneuraminic acid (NeuNAc), the most naturally abundant sialic acid, is incorporated as the terminal residue of mammalian cell surface glycoconjugates and acts as a key facilitator of cellular recognition, adhesion and signalling. Several pathogenic bacteria similarly express NeuNAc on their cell surfaces, allowing evasion of their host's immune system. Prokaryotic NeuNAc biosynthesis proceeds via condensation of phosphoenolpyruvate (PEP) with N-acetylmannosamine (ManNAc), a reaction catalysed by the domain-swapped homodimeric enzyme, N-acetylneuraminic acid synthase (NeuNAcS). Conversely, the mammalian orthologue, N-acetylneuraminic acid 9-phosphate synthase (NeuNAc 9-PS) utilises the phosphorylated substrate N-acetylmannosamine 6-phosphate (ManNAc 6-P) in catalysis. Here we report an investigation into the determinants of substrate specificity of human NeuNAc 9-PS, using model-guided mutagenesis to delineate binding interactions with ManNAc 6-P. Modelling predicts the formation of a domain-swapped homodimer as observed for bacterial variants, which was supported by experimental small angle X-ray scattering. A number of conserved residues which may play key roles in the selection of ManNAc 6-P were identified and substituted for alanine to assess their function. Lys290 and Thr80 were identified as a putative phosphate binding pair, with the cationic lysine residue extending into the active site from the adjacent chain of the dimeric enzyme. Substitution of these residues results in a significant loss of activity and reduced affinity for ManNAc 6-P. These residues, along with the electropositive β2α2 loop, are likely to facilitate the PEP dependent binding and stabilisation of ManNAc 6-P. By utilising a phosphorylated sugar-substrate, the mammalian enzyme gains considerable catalytic affinity advantage over its bacterial counterpart.


Exploring the binding mechanism of β-resorcylic acid with calf thymus DNA: Insights from multi-spectroscopic, thermodynamic and bioinformatics approaches.
β-resorcylic acid (BR) is a phytochemical which is widely used in the food industry as a flavouring agent and preservative. It has also been found to exhibit antibacterial action against several types of food-borne bacteria. DNA is the main molecular target for many small molecules of therapeutic importance. Hence, the interest is rapidly growing among the researchers to elucidate the interaction between small molecules and DNA. Thus, paving the way to design novel DNA-specific drugs. In this study, an attempt was made to examine the mechanism of binding of BR with calf thymus DNA (ctDNA) with the help of various experiments based on spectroscopy and in silico studies. The spectroscopic studies like UV absorption and fluorescence affirmed the complex formation between BR and ctDNA. The observed binding constant was in the order of 103 M-1 which is indicative of the groove binding mechanism. These findings were further verified by dye-displacement assay, potassium iodide quenching, urea denaturation assay, the study of the effect of ssDNA, circular dichroism and DNA thermal denaturing studies. Different temperature-based fluorescence and isothermal titration calorimetry (ITC) experiments were employed to evaluate thermodynamic parameters. The analysis of thermodynamic parameters supports the enthalpically driven, exothermic and spontaneous nature of the reaction between BR and ctDNA. The forces involved in the binding process were mainly found to be hydrogen bonding, van der Waals and hydrophobic interactions. The results obtained from the molecular docking and molecular dynamics (MD) simulation were consistent with the in vitro experiments, which support the groove binding mode of BR with ctDNA.


Lip repositioning surgery for gummy smile: 6-month clinical and radiographic lip dimensional changes.
The present case series aimed to examine lip repositioning surgery (LRS) outcomes related to changes in external and internal upper lip (UL) dimensions, utilizing both conventional clinical and novel radiographic approaches. Patients (n = 13) diagnosed with hypermobile UL (>8-mm mobility during smile) and excessive gingival display (≥4-mm) were included and assessed at baseline and 6 months postoperatively. Clinical parameters at rest included total lip and internal lip length (vestibular depth). At maximum smile included total lip, philtrum (ergotrid), and vermilion lengths. Cephalometric parameters included anterior maxillary height; lip length; nasolabial angle; anteroposterior lip thickness; internal lip length (vestibular depth); and vestibular fornix position (using novel approach employing radiopaque marker). Linear mixed-effect models, Pearson's correlation, and linear regression were used for statistical analyses. LRS did not affect total UL length at rest (p = 0.418). It resulted in significant internal UL length decrease (-3.8 ± 2.1 mm, p < 0.001) and significant increases of vermilion length (1.9 ± 1.0 mm, p < 0.001) and anteroposterior lip thickness (0.7 ± 0.7 mm, p = 0.002). The clinical and radiographic measurements of total UL length at rest (r ≥ 0.734) and of internal UL length (r ≥ 0.737), and the two radiographic assessments of vestibular depth (r = 0.842), were strongly correlated. LRS resulted in significant decrease of vestibular depth/internal UL length and in significant increases of UL vertical vermilion length and UL anteroposterior thickness, without affecting total UL length at rest. The documented lip dimensional outcomes should help practitioners when treatment-planning LRS and counseling patients seeking treatment for hypermobile UL.


Preparation and cell activities of lactosylated curdlan-triornithine nanoparticles for enhanced DNA/siRNA delivery in hepatoma cells.
A long-anticipated cancer therapy would deliver the right type of therapeutic agents to the target in control with minimal systemic toxicity. The purpose of this study was to prepare lactosylated curdlan-triornithine nanocarriers (CTOLs), and target deliver gene to hepatoma cells. Structures and biophysical properties had been elucidated with physical and chemical methods. The results revealed that those functionalized polymers can completely condense the gene into spherical nanoparticles. Cytotoxicity assay, GFP-pDNA and siRNA transfection in vitro were implemented successively. Observations showed that CTOL 20% with the highest lactose acid substitution degree targeted delivered gene into HepG2 cells over expressing ASGPR receptors and had pretty gene knockdown efficiency over 70%. Meanwhile, the carriers showed excellent biocompatibility. Our studies demonstrated that CTOLs with lower toxicity and higher gene binding capacity may serve as a potential valuable platform that can be tailored to target the liver cancer cells for therapeutic gene.


Totally implantable intrathoracic ventricular assist device.
A totally implantable, intrathoracic electrohydraulic ventricular assist device (EVAD) is being developed for permanent use or as a bridge to transplantation. The blood pump with 70-mL nominal stroke volume, volume displacement chamber, reversible turbine, internal electronics and infrared diaphragm position sensor are combined in one compact unit (unified system). The size and geometry are based on human anatomic measurements and fluid dynamic studies. A transcutaneous energy transfer powers the system and recharges the implantable nickel-cadmium battery pack. Autotuning circuitry optimizes energy transfer efficiency over a range of transcutaneous energy transfer coil spacings and misalignments. An infrared diaphragm position sensor detects end-systole and diastole points. In vitro and acute in vivo tests have demonstrated flow rates greater than 6 L/min. The transcutaneous energy transfer system demonstrated power transfer efficiencies of 60% to 80% for power demands from 5 to 60 W. Thirteen systems are currently undergoing durability testing; one has run for more than 750 days failure-free. The system recently sustained circulation in an acute calf implantation for 96 hours. Results of the in vitro and in vivo testing to date have demonstrated that the developed system can function effectively as a totally implantable ventricular assist device. Chronic in vivo evaluation is planned.


Divergence in expression of candidate genes for the smoltification process between juvenile resident rainbow and anadromous steelhead trout.
Rainbow and steelhead trout (Oncorhynchus mykiss), among other salmonid fishes, exhibit tremendous life history diversity, foremost of which is variation in migratory propensity. While some individuals possess the ability to undertake an anadromous marine migration, others remain resident in freshwater throughout their life cycle. Those that will migrate undergo tremendous physiological, morphological, and behavioral transformations in a process called smoltification which transitions freshwater-adapted parr to marine-adapted smolts. While the behavior, ecology, and physiology of smoltification are well described, our understanding of the proximate genetic mechanisms that trigger the process are not well known. Quantitative genetic analyses have identified several genomic regions associated with smoltification and migration-related traits within this species. Here we investigate the divergence in gene expression of 18 functional and positional candidate genes for the smoltification process in the brain, gill, and liver tissues of migratory smolts, resident parr, and precocious mature male trout at the developmental stage of out-migration. Our analysis reveals several genes differentially expressed between life history classes and validates the candidate nature of several genes in the parr-smolt transformation including Clock1α, FSHβ, GR, GH2, GHR1, GHR2, NDK7, p53, SC6a7, Taldo1, THRα, THRβ, and Vdac2.


Total and bioavailable arsenic concentration in arid soils and its uptake by native plants from the pre-Andean zones in Chile.
Arsenic is the most important contaminant of the environment in northern Chile. Soil samples and plant organs from three native plant species, Pluchea absinthioides, Atriplex atacamensis and Lupinus microcarpus, were collected from arid zones in order to determine the total and bioavailable arsenic concentrations in soils and to assess the bioconcentration factor (BCF) and transport index (Ti) of arsenic in the plants. Total arsenic concentrations in soils (pH 8.3-8.5) where A. atacamensis and P. absinthioides were collected, reached levels considered to be contaminated (54.3 ± 15.4 and 52.9 ± 9.9 mg kg⁻¹, respectively), and these values were approximately ten times higher than in soils (pH 7.6) where L. microcarpus was collected. Bioavailable arsenic ranged from 0.18 to 0.42% of total arsenic concentration. In the three plant species, arsenic concentration in leaves were significantly (p ≤ 0.05) higher than in roots. L. microcarpus showed the highest arsenic concentration in its leaves (9.7 ± 1.6 mg kg⁻¹) and higher values of BCF (1.8) and Ti (6.1), indicating that this species has a greater capacity to accumulate and translocate the metalloid to the leaf than do the other species.


Temporal surveillance of the humoral immunity against influenza vaccine in the elderly over 9 consecutive years.
The effect of age on declining immunity is well established, but its influence on humoral responses to influenza vaccines is still debated. To compare prospectively the immunogenicity of an influenza vaccine in elderly and healthy control subjects and to search for correlations between this specific humoral protection and clinical and virological parameters. A prospective study of the humoral response to influenza vaccine was conducted over 9 consecutive years in the long-term care units of the Saint-Etienne University Hospital, France. Antibodies directed against the vaccinal strains in an inactivated trivalent vaccine were tested by radial haemolysis before and 1 month after 477 and 242 cumulative annual vaccinations in elderly people and in healthy controls, respectively. During the last 6 years of the study, clinical samples from patients with fever > or =38 degrees C were tested systematically for the diagnosis of an influenza infection. A significant rise in anti-A/H3N2 antibody titres was observed in 49.3% of the elderly subjects and in 48.3% of the controls (not significant). The rises for the A/H1N1 and B strains were 31.4 and 39.2% (p < 0.001) and 30.6 and 40.5 (p < 0.001), respectively. When control subjects under 31 years old were excluded, no significant difference was recorded for any strain. Only 3.9% of the vaccinated elderly experienced any clinical influenza infection as defined by fever >/=38 degrees C and virological proof. The humoral response to influenza immunization is not impaired in the elderly compared with middle-aged controls, and the incidence of febrile episodes due to influenza is low in this vaccinated elderly population. These findings provide further evidence supporting the recommendation for annual influenza vaccination in the elderly.


Cytogenetic studies of adipose tissue tumors. II. Recurrent reciprocal translocation t(12;16)(q13;p11) in myxoid liposarcomas.
Detailed chromosome studies, briefly reported previously, from short-term cultures of tumor cells from myxoid liposarcomas are reported. A common reciprocal translocation, t(12;16)(q13;p11), was found in three cases and a complex t(1;12;16)(p11;q13;p11) in the fourth one. This nonrandom primary change, not described before in solid tumors, could characterize the myxoid form of liposarcoma. The involvement of a closely located breakpoint on chromosome #12 in a reciprocal t(3;12)(q28;q14) described in a lipoma in the previous article of this series, suggests a common basis in the biological process of proliferation of tumors sharing a common histogenesis.


Human herpesvirus 6-specific T-cell immunity in allogeneic hematopoietic stem cell transplant recipients.
Human herpesvirus 6 (HHV-6) can reactivate after allogeneic hematopoietic stem cell transplant (allo-HSCT) and may lead to severe symptoms. HHV-6-specific immune responses after HSCT are largely unexplored. We conducted a prospective observational study on 208 consecutive adult patients who received allo-HSCT to investigate HHV-6 reactivations and specific immune responses. Interferon gamma-producing HHV-6-specific T cells were quantified using enzyme-linked immunospot assay (ELISpot). HHV-6 reactivation occurred in 63% of patients, at a median of 25 days from allo-HSCT. Only 40% of these presented a clinically relevant infection, defined by the presence of classical HHV-6 end-organ diseases (EODs), based on European Conference on Infections in Leukaemia (ECIL) guidelines, and other possible HHV6-related EODs. Using multivariate analysis, we identified risk factors for HHV-6 reactivation: previous allo-HSCT, posttransplant cyclophosphamide (PT-Cy), and time-dependent steroids introduction. The use of PT-Cy and steroids were associated with clinically relevant infections, whereas higher CD3+ cell counts seemed to be protective. Interestingly, circulating HHV-6-specific T cells were significantly higher in patients with reactivated virus. Moreover, HHV-6-specific T-cell responses, quantified at >4 days after the first viremia detection, predicted clinically relevant infections (P < .0001), with higher specificity (93%) and sensitivity (79%) than polyclonal CD3+ cells per μL. Overall survival and transplant-related mortality were not affected by time-dependent HHV-6 reactivation, whereas a significant association was observed between clinically relevant infections and acute graft-versus-host disease. These results shed light on the role of HHV-6 in allo-HSCT and may affect HHV-6 monitoring and treatment.


Interspecies variation in ritodrine metabolism.
The metabolism of ritodrine has been studied in the rat, both in vitro and in vivo, and in the in vivo pregnant baboon, with the use of tritium-labeled drug as a probe. Combined enzymatic degradation and radiochromatography of the radioactive components of bile and urine show that ritodrine undergoes significant Phase l metabolism in addition to conjugation to both sulfate and glucuronide, as previously reported. The presence of more than one conjugate is shown, and evidence for major interspecies variation in patterns of metabolism and conjugation is presented, with comments on the applicability of results to human clinical use.


Development of solar cell for large area position detection: proof of concept.
Detecting and analyzing a moving body position are helpful in many fields, such as medicine, sports performance, virtual reality and many more. Therefore, researchers try to develop a tool or a system that helps to detect the motion and tracking its position. This paper shows how a Si solar cell can be modified to function as a Position Sensitive Detector (PSD), which could be used as a large area detector in a position detection system. To develop the new detector, we modeled and simulated the modified solar cell by TCAD simulation tools to calculate the detected photocurrent as a function of the position of an incident laser beam sourced by the moving object. Further, an optical position detection system is implemented containing the modified solar cell, a signal amplifier and a microcontroller. The output is then displayed on a Laptop. By measuring the same simulated output photocurrents, it is found that the measured system output matches the simulation results. This proposed position detection system is relatively cheap because it does not contain high precision optical image building components such as lenses and mirrors. Besides, the proposed system could substitute the optical system by using a large area PSD made from a broad array of solar cells. The electronics are also much more straightforward than those in systems based on image processing. So, it has a high-speed response. The error assessment of the proposed system showed a low position detection error of less than 10%.


Diagnosis of pentacuspid aortic valve with severe regurgitation using three-dimensional transesophageal echocardiography.
Monocuspid and quadricuspid aortic valves are a rare congenital valve malformation, and less common is the pentacuspid aortic valve (PAV). Echocardiography is a helpful noninvasive technique for their diagnosis. In this article, we describe a 48-year-old female patient with a PAV and severe aortic regurgitation that was diagnosed using three-dimensional transesophageal echocardiography.


Lack of value of routine preoperative bone and liver scans in cystectomy candidates.
A retrospective review of 341 patients with bladder cancer revealed 58 candidates for cystectomy. These patients were evaluated preoperatively by radionuclide bone and/or liver scans in an attempt to increase the accuracy of clinical staging. In the face of a normal history, physical examination, liver function tests or serum alkaline phosphatase routine preoperative bone and liver scans in cystectomy candidates did not contribute significantly to clinical staging or choice of treatment. Since liver and bone scans add significantly to the cost of the illness their use should not be routine but reserved only for those special cases when they are indicated.


Biodegradable polydioxanone stents: a new option for therapy-resistant anastomotic strictures of the colon.
To assess the outcome of self-expandable, biodegradable stent insertion for anastomotic strictures following treatment for rectosigmoid carcinoma. Three male patients (median age 66) developed benign strictures after radiotherapy and resection of a recto-sigmoid carcinoma. These were resistant to balloon dilatation and prevented stoma reversal. Biodegradable stent insertion was performed as an experimental treatment on a named-patient basis with approval of the institutional review board. Patients had monthly follow-up with endoscopy and contrast medium enemas to monitor performance and degradation of the stents. All stents were placed successfully without complications after pre-dilatation to 20 mm under fluoroscopic guidance. Stent degradation occurred in all patients 4-5 months following implantation, and long-term anastomotic patency was demonstrated in all. This allowed reversal of the colostomy and physiological defecation in two patients. Reversal was not undertaken in one due to subsequent development of liver metastases. No stent migration or occlusion occurred. Biodegradable stents can maintain an adequate lumen across anastomotic strictures resistant to balloon dilatation. They seem to allow stricture re-modelling resulting in maintained dilatation after degradation. This potentially allows reversal of a colostomy, which might otherwise be prevented by stricture recurrence.


Thymulin (FTS-Zn) induced in vitro modulation of T cell subsets markers on lymphocytes from rheumatoid arthritis and systemic lupus erythematosus patients.
Perturbations in T cells and T cell subsets of peripheral blood lymphocytes were looked for, using monoclonal antibodies, in nine patients with rheumatoid arthritis (RA) and four patients with systemic lupus erythematosus (SLE). All SLE patients were in an acute phase of their disease, but had not yet received steroids. Seven of the nine RA patients presented an active illness, recently diagnosed in five cases, and received no steroids nor D-penicillamin. T cell subsets alterations responsible for abnormal values of the OKT4 +/OKT8 + immunoregulatory ratio, were improved by in vitro incubation of the lymphocytes with synthetic thymulin in eight out of nine RA patients. No significant modification occured for SLE patients' lymphocytes. These results support the possible beneficial role of thymulin in the treatment of rheumatoid arthritis.


The therapeutic efficacy of α-pinene in an experimental mouse model of allergic rhinitis.
In the present study, the therapeutic effect and underlying mechanism of α-pinene (α-PN) in the ovalbumin (OVA)-sensitized allergic rhinitis (AR) model were investigated. Our results showed that pretreatment with α-PN caused a decrease in clinical symptoms, including a decrease in the number of nasal, eye, and ear rubs, and spleen weight in the OVA-sensitized mice. The level of interleukin (IL)-4 was decreased on the spleen tissue of α-PN treated mice. Pretreatment with α-PN significantly decreased levels of nasal immunoglobulin E. Protein levels of tumor necrosis factor-α, intercellular adhesion molecule-1, and macrophage inflammatory protein-2 were decreased by the administration of α-PN in the nasal mucosa of the OVA-sensitized mice. The increased numbers of eosinophils and mast cells infiltrating the nasal mucosal tissue of mice with AR were decreased following oral administration of α-PN. Post-treatment with α-PN 1h after OVA challenge also resulted in a significant reduction of clinical symptoms and IgE levels. In addition, the expression and phosphorylation of receptor-interacting protein 2 (RIP2) and IκB kinase (IKK)-β and activation of nuclear factor-κB (NF-κB), and caspase-1 were all increased in the activated human mast cell line, HMC-1 cells, however, increased activations of RIP2, IKK-β, NF-κB, and caspase-1 were inhibited by treatment with α-PN. Taken together, we suggest that α-PN is a promising anti-allergic agent and may be useful in the clinical management of AR.


Proniosomes as a Carrier System for Transdermal Delivery of Clozapine.
The current study aimed to formulate the clozapine (CLZ) loaded proniosomal gel (PN) and evaluate it's in vitro release, ex vivo permeation and gel properties. CLZ is a BCS class II drug with low bioavailability of 27% and severe adverse drug reactions (ADRs) due to frequent dosing. Proniosomes offer a versatile pro-vesicular approach with potential in transdermal drug delivery. PN-CLZ gel was prepared by the coacervation phase separation method utilizing span-60, cholesterol and lecithin. Optimization of PN gel was done by hit & trial method and the formulations were characterized for particle size, entrapment efficiency (EE), polydispersity index (PDI) and zeta potential (ZP). The optimized formulation had the highest entrapment efficiency of 90% and the average particle size of approx. 325 nm. PDI reflected homogeneity in the formulation. ZP was -59.76 mV, high enough to indicate a stable formulation. The in vitro release studies manifested a sustained release behavior of clozapine from the proniosomal gel. The ex vivo permeation showed noteworthy permeation of the drug through stratum corneum with a steady state flux of 18.26 ug/cm2/hr. The optimized gel was analyzed for pH, spreadability, bioadhesion and rheology. The results suggested that clozapine could be effectively loaded into proniosomal gel for administration through skin.


Stress, anxiety and depression among gastronomes: association with workplace mobbing and work-family interaction.
The work in commercial restaurant kitchens is characterized by many labor´s demands and strict commands that can cause damage to the mental health of gastronomes. The aim of this study was to verify the presence of stress, anxiety, and depression among gastronomy workers and associate them with the presence of mobbing at work. Still, it sought to evaluate the work-family interference and test its mediating role in the relationship between mobbing and psychopathology indicators. This is an observational-analytical, cross-sectional study with a quantitative approach, in which 160 gastronomes participated (59.4% women), with an average age of 30.81 years. All answered a Sociodemographic and Labor Data Questionnaire, Negative Acts at Work Questionnaire, Depression Anxiety and Stress Scale, and Work-Family Interaction Scale, whose data were analyzed using descriptive and inferential statistics. A positive association was found between bullying and indicators of stress, anxiety, and depression, as well as negative interference between work-family and family-work with the same indicators. It was also observed the mediating effect of negative interference from work in family, in the relationship between mobbing and indicators of stress, anxiety, and depression. It was concluded, therefore, that the experience of mobbing affects the family and intensifies the psychological illness in gastronomes.


AI reveals insights into link between CD33 and cognitive impairment in Alzheimer's Disease.
Modeling biological mechanisms is a key for disease understanding and drug-target identification. However, formulating quantitative models in the field of Alzheimer's Disease is challenged by a lack of detailed knowledge of relevant biochemical processes. Additionally, fitting differential equation systems usually requires time resolved data and the possibility to perform intervention experiments, which is difficult in neurological disorders. This work addresses these challenges by employing the recently published Variational Autoencoder Modular Bayesian Networks (VAMBN) method, which we here trained on combined clinical and patient level gene expression data while incorporating a disease focused knowledge graph. Our approach, called iVAMBN, resulted in a quantitative model that allowed us to simulate a down-expression of the putative drug target CD33, including potential impact on cognitive impairment and brain pathophysiology. Experimental validation demonstrated a high overlap of molecular mechanism predicted to be altered by CD33 perturbation with cell line data. Altogether, our modeling approach may help to select promising drug targets.


Localization of various secretory phospholipase A2 enzymes in male reproductive organs.
Current evidence suggests the presence of transcripts for several secretory phospholipase A(2) (sPLA(2)) enzymes in male genital organs. In this study, we examined by immunohistochemistry the localization of group IIA, IIC, IID, IIE, IIF, V and X sPLA(2)s in male genital organs. In sPLA(2)-IIA-deficient C57BL/6 mouse testis, sPLA(2)-IIC, -IID, -IIE, -IIF, -V and -X were diversely expressed in spermatogenic cells within the seminiferous tubules. Immunoblotting revealed the presence of these sPLA(2)s in mouse spermatozoa. In addition, sPLA(2)-IIF, -V and -X were localized in the interstitial Leydig cells. The same set of sPLA(2)s was detected in a mouse cultured Leydig cell line, and adenovirus-mediated transfer of these sPLA(2)s into Leydig cells resulted in increased prostaglandin production. sPLA(2)-IIC, -IID, -IIE, -IIF, -V and -X were also detected diversely in the epithelium of the epididymis, vas deferens, seminal vesicles, and prostate. In a sPLA(2)-IIA-positive FVB strain, weak expression of sPLA(2)-IIA was detected in Leydig cells. Notable differences in the sPLA(2) expression profiles were found in the seminal vesicles and prostate between mice and humans. Taken together, individual sPLA(2)s exhibit distinct or partially overlapping localizations in male reproductive organs, suggesting both specific and redundant functions.


The Interplay Between Titin, Polygenic Risk, and Modifiable Cardiovascular Risk Factors in Atrial Fibrillation.
Common and rare variants, including those in the gene for the cardiac structural protein titin (TTN), have been implicated in the risk of developing atrial fibrillation (AF). However, the effect of genetic variants on risk of AF compared with established modifiable risk factors is unclear. The objective of this study was to evaluate the risk of AF and associated cardiovascular complications in TTN variant carriers and examine interactions between TTN variants or common variants and modifiable AF risk factors. We used whole exome sequencing data of 49,881 individuals and genotyping data of 408,572 individuals from the UK Biobank to examine the associations of TTN variants, polygenic risk, and 4 risk factors (hypertension, diabetes, obesity, and smoking) with AF. Adjusted hazard ratios (aHRs) were calculated with the use of Cox proportional hazards models. TTN variant carrier status was associated with a higher risk of AF (aHR 2.10, 95% CI 1.59-2.79; P = 2.54 × 10-7) and higher risk of dilated cardiomyopathy in AF patients (aHR 10.39, 95% CI 5.31-20.33; P = 8.37 × 10-12). We identified additive effects between TTN variants and polygenic risk with hypertension, diabetes, obesity, and smoking on the risk of AF. Genetic and modifiable cardiovascular risk factors contribute to the probability of developing AF. Our findings highlight the potential utility of incorporating data from targeted sequencing or genotyping of common variants to further inform AF risk stratification and aggressive management of modifiable cardiovascular risk factors.


Regional coordinators of Sao Paulo State prisons in tuberculosis and HIV coinfection care.
to analyze the care provided to individuals with Tuberculosis (TB)-HIV coinfection in prison units in the state of São Paulo, according to the regional coordination of prisons. cross-sectional study conducted between 2016 and 2018. A structured questionnaire was applied to 112 directors or health professionals from 168 prison units. Data were analyzed by frequency distribution and multiple correspondence analysis. 92.9% of participants reported active search for respiratory symptoms, 89.3% offer the directly observed treatment (DOT) for all TB cases, 95.5% anti-HIV testing for all inmates, 92.9% offer HIV follow-up in specialized care services and 59.8% antiretroviral drugs for cases of coinfection. An association was identified between the Northwest and Central regional coordinations and deficient human resources and low performance of actions for the diagnosis and follow-up of cases. although most prison units perform planned actions for the care of coinfected persons, some places need support to guarantee access to these actions.


Systemic hypertension among women with uterine leiomyomata: potential final common pathways of target end-organ remodeling.
The uterus and the heart share a common structure and may remodel in a similar fashion, albeit temporally distinct. The authors investigated the prevalence of systemic hypertension in women with uterine leiomyomata (fibroids) and compared the prevalence in women undergoing hysterectomy for other reasons as well as in age-matched women from the National Health and Nutrition Examination Survey III (NHANES III). A total of 584 women, 205 with leiomyomata in 1999 (group A) and 379 who underwent hysterectomy for a variety of reasons in 2000 (group B) at Advocate Christ Medical Center were included. Presence of leiomyomata was confirmed by pathology. Hypertension was defined as blood pressure > or = 140/90 mm Hg or history of hypertension with or without medication use. The prevalence of hypertension in group A and B patients with leiomyomata compared with NHANES III overall was 48.6% vs. 24% (p<0.001), in African Americans 55.5% vs. 32.4% (p<0.001), and in Caucasians 51.1% vs. 23.3% (p<0.001). Leiomyomata were more frequent among hypertensive than normotensive women (57% vs. 27%). Caucasian and African-American women with leiomyomata were significantly younger and more likely to use hormone replacement therapy than others. Thus there appears to be an association between leiomyomata and hypertension, which needs to be explored in future prospective trials.


Delayed feedback control requires an internal forward model.
Biological motor control provides highly effective solutions to difficult control problems in spite of the complexity of the plant and the significant delays in sensory feedback. Such delays are expected to lead to non trivial stability issues and lack of robustness of control solutions. However, such difficulties are not observed in biological systems under normal operating conditions. Based on early suggestions in the control literature, a possible solution to this conundrum has been the suggestion that the motor system contains within itself a forward model of the plant (e.g., the arm), which allows the system to 'simulate' and predict the effect of applying a control signal. In this work, we formally define the notion of a forward model for deterministic control problems, and provide simple conditions that imply its existence for tasks involving delayed feedback control. As opposed to previous work which dealt mostly with linear plants and quadratic cost functions, our results apply to rather generic control systems, showing that any controller (biological or otherwise) which solves a set of tasks, must contain within itself a forward plant model. We suggest that our results provide strong theoretical support for the necessity of forward models in many delayed control problems, implying that they are not only useful, but rather, mandatory, under general conditions.


S-thiolation mimicry: quantitative and kinetic analysis of redox status of protein cysteines by glutathione-affinity chromatography.
S-Glutathionylation is emerging as a novel regulatory and adoptive mechanism by which glutathione (GSH or GSSG) conjugation can modify functionally important reactive cysteines in redox-sensitive proteins. The dynamics of generation and reversal of this modification in cells is poorly understood. This study describes the ability and applicability of GSH- and GSSG-affinity matrices to quantitatively bind proteins which harbor reactive cysteines and undergo glutathionylation. We showed that purified proteins, known to be modified by S-thiolation, bind to these matrices, are selectively eluted by dithiothreitol and rapidly incorporate biotin-labeled GSH or GSSG in vitro. Chromatography of extracts from tumor cells that had been treated with oxidants (diamide, H(2)O(2), tert-butyl hydroperoxide) on GSH-Sepharose showed the specific binding of many proteins, whose levels increased transiently (2- to 6-fold) soon after treatments. However, when these cells were post-incubated in drug/oxidant-free media, protein binding decreased gradually to control levels over 3-12h, thereby demonstrating the central role of cysteine redox status in the binding. Immunoblotting of eluates from GSH-Sepharose showed the presence of known (actin, ubiquitin-activating enzyme E1, NF-kappaB, and proteasome) and putative (p53, glutathione-S-transferase P1) targets for glutathionation. After oxidant withdrawal, many of these proteins displayed unique kinetics in their loss of binding to GSH-matrix, reflecting their differential abilities to recover from cysteine redox changes in cellular milieu. Further, we correlated the kinetics of S-thiolation susceptibility of the proteasome and ubiquitin-E1 proteins with altered levels of protein ubiquitination in H(2)O(2)-treated cells. Our study reveals the hitherto underutilized ability of glutathione matrices for analyzing the kinetics of cysteine redox in cellular proteins and allows easy identification of S-thiolatable proteins.


Synthetic derivatives of aromatic abietane diterpenoids and their biological activities.
Naturally occurring aromatic abietane diterpenoids (dehydroabietanes) exhibit a wide range of biological activities. A number of synthetic studies aimed at modifying the abietane skeleton in order to obtain new potential chemotherapeutic agents have been reported. In this study, the biological activities of synthetic derivatives of aromatic abietane diterpenoids are reviewed.


Ion-exchange chromatography method for the purification of genomic DNA fraction from Mycobacterium bovis Bacillus Calmette-Guérin.
The goal of this study was to provide practical strategies for purifying genomic DNA fraction from Mycobacterium bovis Bacillus Calmette-Guérin (BCG-DNA) by ion-exchange chromatography. A multistep process was developed to purify BCG-DNA. The process consisted of sonication, heating, trypsin digestion, ion-exchange chromatography, gel-filter chromatography, and lyophilization. After ion-exchange chromatography, BCG-DNA was highly purified and possessed potent biological effects. The methods described were efficient and had good reproducibility. Further, this was the first reported chromatography method to purify BCG-DNA.


A prospective, randomized, double-blinded study of assisted hatching in women younger than 38 years undergoing in vitro fertilization.
To determine whether assisted hatching is beneficial to IVF patients younger than 38 years whose embryos have a thickened zona pellucida (ZP). Prospective, randomized, double-blinded, crossover study. University-based infertility center. One hundred twenty-one women less than 38 years of age, undergoing IVF at Washington University between April 2004 and February 2007, with ZP thickness > or =13 microm for any embryos. Measurement of ZP thickness in embryos undergoing IVF; randomization of women with embryos with ZP thickness > or =13 microm to no procedure or assisted hatching performed by acidic Tyrode's solution. Clinical intrauterine pregnancy rate, implantation rate, spontaneous pregnancy loss, and live birth rate. Baseline characteristics and ZP thickness were not significantly different between the two study arms (hatched and unhatched). No significant differences were observed between hatched and unhatched patients in the rates of clinical pregnancy (47% vs. 50% respectively) or live birth (46% vs. 45% respectively). Further, no significant differences were noted between hatched and unhatched groups in rates of spontaneous abortions, monozygotic twinning, dizygotic twinning, chromosomal abnormalities, or ectopic gestations. In addition, mean ZP thickness did not have a significant effect on pregnancy. In patients younger than 38 years with embryos with ZP thickness of > or =13 microm, assisted hatching does not improve the rates of implantation, clinical pregnancy, or live birth, and thus does not appear to offer any benefit to patients in this age group undergoing IVF.


Evaluation of Exposure to Radiofrequency Electromagnetic Fields from Smart Utility Meters operating at 868 MHz.
Power density and duty factor values were measured around smart utility meters operating at 868 MHz under laboratory-controlled conditions. The maximum 6-min averaged exposure recorded was 0.1 mWm-2 , which is less than 0.0024% of the corresponding 1998 ICNIRP general public reference level. Duty factors measured were less than 2.8%. This study found that the exposure contribution from Zigbee smart meter devices operating at 868 MHz is generally lower than, if not similar to, those operating at 2.4 GHz. © 2023 Crown copyright. Bioelectromagnetics published by Wiley Periodicals LLC on behalf of Bioelectromagnetics Society.


Isolated leishmanial lymphadenopathy - a rare type of leishmaniasis in India: a case report.
A patient presented with isolated, soft to firm, inguinal swelling since childhood clinically thought to be a benign lipomatous lesion. Fine-needle aspiration of the swelling revealed amastigote form of Leishmania donovani in a background of reactive lymphoid hyperplasia. Excision of the swelling resulted in reversal of positive Aldehyde test. Isolated leishmanial lymphadenopathy in an immunocompetent person, is a rare manifestation of leishmaniasis in India. The possible role of transplacental transmission is discussed.


A method for producing hollow cone illumination electronically in the conventional transmission microscope.
An electronic device manipulates the primary beam in the conventional transmission microscope to produce a hollow cone of illumination with its apex located at the specimen. The device uses the existing tilt coils of the microscope, and modulates the D.C. signals to both x and y tilt directions simultaneously with various waveforms to produce Lissajous figures in the back-focal plane of the objective lens. Electron diffraction patterns can be recorded which reflect the manner in which the direct beam is tilted during exposure of a micrograph. In the bright-field imaging mode the device provides a microscope transfer function without zeros in all spatial directions and has been used to obtain high resolution images which are also free from the effect of chromatic aberration. A standard second condenser aperture is employed and the width of the cone annulus is readily controlled by defocusing the second condenser lens. The cone azimuthal angle is also controlled electronically; hence the device can also be used in the dark-field imaging mode. This device has been applied to imaging both amorphous and crystalline materials including biomolecular specimens.


Is subscapularis repair associated with better outcome compared to non-repair in reverse total shoulder arthroplasty? A systematic review of comparative trials.
We aimed to investigate whether combined reverse total shoulder arthroplasty (RTSA) and subscapularis repair leads to improved clinical and functional outcome in comparison with RTSA alone. Two reviewers independently conducted a systematic search according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) using the MEDLINE/PubMed database and the Cochrane Database of Systematic Reviews. These databases were queried with the terms "reverse" AND "shoulder" AND "arthroplasty" AND "with" AND "subscapularis" AND "repair". From the 72 initial studies, we finally chose five studies which were eligible to our inclusion-exclusion criteria. The total mean modified Coleman methodology test was 55/100 (range: 47/100 to 60/100). The eligible studies included 1087 patients, in total. Regarding the subjective functional scores as well as range of motion (ROM), the differences amongst groups were insignificant in almost all studies. The mean complications' rate of the repair group was 10.4%, whereas the respective rate of the nonrepair group was 10.2%. All studies concluded that the repair of subscapularis did not affect the complications' rate of patients who were treated with RTSA. The mean dislocations' rates of the repair and the nonrepair group were 1.5% and 2.3%, respectively. Although subscapularis repair was proven safe and effective for the augmentation of RTSA, it did not offer any additional clinical or functional benefit in the outcome of patients treated with lateralized RTSA. Therefore, it is not supported its routine use for patients who have a preoperatively sufficient subscapularis tendon.


Ancestral archaea expanded the genetic code with pyrrolysine.
The pyrrolysyl-tRNA synthetase (PylRS) facilitates the cotranslational installation of the 22nd amino acid pyrrolysine. Owing to its tolerance for diverse amino acid substrates, and its orthogonality in multiple organisms, PylRS has emerged as a major route to install noncanonical amino acids into proteins in living cells. Recently, a novel class of PylRS enzymes was identified in a subset of methanogenic archaea. Enzymes within this class (ΔPylSn) lack the N-terminal tRNA-binding domain that is widely conserved amongst PylRS enzymes, yet remain active and orthogonal in bacteria and eukaryotes. In this study, we use biochemical and in vivo UAG-readthrough assays to characterize the aminoacylation efficiency and substrate spectrum of a ΔPylSn class PylRS from the archaeon Candidatus Methanomethylophilus alvus. We show that, compared with the full-length enzyme from Methanosarcina mazei, the Ca. M. alvus PylRS displays reduced aminoacylation efficiency but an expanded amino acid substrate spectrum. To gain insight into the evolution of ΔPylSn enzymes, we performed molecular phylogeny using 156 PylRS and 105 pyrrolysine tRNA (tRNAPyl) sequences from diverse archaea and bacteria. This analysis suggests that the PylRS•tRNAPyl pair diverged before the evolution of the three domains of life, placing an early limit on the evolution of the Pyl-decoding trait. Furthermore, our results document the coevolutionary history of PylRS and tRNAPyl and reveal the emergence of tRNAPyl sequences with unique A73 and U73 discriminator bases. The orthogonality of these tRNAPyl species with the more common G73-containing tRNAPyl will enable future efforts to engineer PylRS systems for further genetic code expansion.


A highly sensitive and quantitative time resolved fluorescent microspheres lateral flow immunoassay for streptomycin and dihydrostreptomycin in milk, honey, muscle, liver, and kidney.
Streptomycin (STR) and dihydrostreptomycin (DHSTR) are clinically widely used in the prevention and treatment of animal diseases. Unreasonable use or abuse can easily cause adverse effects on human health. Thus, it is very necessary to establish a rapid detection method for STR and DHSTR in animal-derived foods. In this study, a time-resolved fluorescent microspheres lateral flow immunoassay (TRFM-LFIA) integrated with a portable fluorescence reader was developed for STR and DHSTR detection. The cut-off values of the TRFM-LFIA for STR and DHSTR in milk/honey/muscle/liver/kidney were both 30/15/80/25/60 μg kg-1, respectively, the limits of detection were 1.10/0.28/2.82/1.52/3.02, 0.75/0.23/1.76/1.21/2.35 μg kg-1, respectively, and the limits of quantitation were 3.62/0.93/9.31/5.02/9.96, 2.48/0.76/5.81/3.99/7.76 μg kg-1, respectively. The recoveries ranged from 80.0% to 120.1%, with coefficient of variation from 2.8% to 14.3%, respectively. The parallel experiment of 25 samples showed excellent correlation (R2 > 0.99) between ELISA kit and TRFM-LFIA. The sample pretreatment is very simple, and the results can be achieved in 8 min. This sensitive, simple, rapid and portable analysis strategy can provide universal technical support for the residue detection of veterinary drugs and even small molecular hazard factors.


Intersectionality: An Understudied Framework for Addressing Weight Stigma.
Obesity is an ongoing public health concern in the U.S. Weight stigma is linked to a number of obesogenic health outcomes, which complicate obesity treatment and prevention. Despite higher rates of obesity in female and minority populations, little research has examined weight stigma in non-white women and men. This study investigated intersectionality in weight stigma and health-related coping responses to stigmatizing experiences across racial groups. In 2015, a total of 2,378 adults completed questionnaires about weight stigma, weight bias internalization, and coping strategies. Analyses were conducted in 2016. No differences in weight stigma emerged as a function of race or gender, but women reported higher weight bias internalization (B=0.19, p=0.004). Further, black men and women reported less weight bias internalization than white men and women (B=-0.43, p=0.009). Compared with white women, black women were less likely to cope with stigma using disordered eating (B=-0.57, p=0.001), whereas Hispanic women were more likely to cope with stigma using disordered eating (B=0.39, p=0.020). Black men were more likely than white men to cope with stigma via eating (B=-0.49, p=0.017). Findings highlight that weight stigma is equally present across racial groups, but that groups internalize and cope with stigma in different ways, which exacerbate health risks. Increased research and policy attention should address stigma as an obstacle in prevention and treatment for obesity to reduce weight-based inequities in underserved populations.


The Intra-Procedural Cortisol Assay During Adrenal Vein Sampling: Rationale and Design of a Randomized Study (I-Padua).
Adrenal vein sampling (AVS) is the gold standard test for the subtyping of primary aldosteronism (PA). This procedure is hampered by unsuccessful bilateral cannulation of adrenal veins in up to two thirds of the cases depending on the cutoff of the selectivity index used. The rapid intra-procedural cortisol assay (IRCA) can increase the rate of bilateral success of AVS. This hypothesis needs to be proven using a randomized prospective study approach. We will therefore evaluate if an IRCA guiding adrenal vein sampling can increase the rate of selectivity and success of adrenal vein catheterization. Consecutive patients with a biochemical diagnosis of PA and seeking surgical cure will be randomized to undergo AVS according to the usual practice with or without IRCA. The primary endpoint of the study will be the rate of bilaterally selective AVS studies, as defined by a value of the selective index >2.00 under baseline (unstimulated) conditions. With a total of 200 patients submitted to AVS, e.g. 100 patients in each arm, the study has 82% power to detect a 18% difference between arms at a two-sided α level =0.05. Given this power the study should allow to conclusively determine if IRCA is useful or not for improving the success rate of AVS. From the clinical standpoint this will be a major accomplishment in the field of the subtyping of PA considering the current disastrous situation regarding the clinical use of AVS.


Proteolytic control of regulated necrosis.
Proteases control most of the physiological processes that occur in a cell. This particularly applies to apoptosis, the most well-studied form of cell death, where proteolysis by cysteine-aspartic proteases (caspases) is the primary mechanism for both initiation and execution of cell suicide. In contrast, the impact of proteolysis on other, non-apoptotic cell death pathways (summarized under the term "regulated necrosis", RN) has long been enigmatic, but has clearly been confirmed by a number of recent groundbreaking discoveries. Here, we review these discoveries and provide an overview on the role of proteolysis in known forms of RN, with a particular focus on necroptosis and pyroptosis, and their regulation by deubiquitinases, apoptotic and inflammatory caspases. This article is part of a Special Issue entitled: Proteolysis as a Regulatory Event in Pathophysiology edited by Stefan Rose-John.


The effects of dummy/pacifier use on infant blood pressure and autonomic activity during sleep.
Dummy/pacifier use is protective for sudden infant death syndrome (SIDS); however, the mechanism/s for this are unknown. As impaired cardiovascular control may be the underlying cause of SIDS, we assessed the effects of dummy/pacifier use on cardiovascular control during sleep within the first 6 months of life. Term infants, divided into dummy/pacifier users and non-dummy/pacifier users, were studied at 2-4 weeks (n = 27), 2-3 months (n = 35) and 5-6 months (n = 31) using daytime polysomnography. Heart rate, blood pressure (BP), heart rate variability (HRV), blood pressure variability (BPV), and baroreflex sensitivity (BRS) were measured in triplicate 1-2-min epochs during quiet and active sleep in the supine and prone positions. Overall, during the non-sucking periods, in the prone position, the BP was higher (10-22 mmHg) in dummy/pacifier users compared to non-users at 2-4 weeks and 5-6 months (p < 0.05 for both). HRV and BRS were higher in dummy/pacifier users compared to non-users at 2-4 weeks (p < 0.05). Active sucking increased HRV and BPV, consistent with increased sympathetic activity in dummy/pacifier users. Higher BP and HRV in dummy/pacifier users indicate increased sympathetic tone, which may serve as a protective mechanism against possible hypotension leading to SIDS; however, these effects were not apparent at 2-3 months, when the risk of SIDS is highest.


[Hirsutism].
The symptom of hirsutism, i.e. excessive sexual hair of the male pattern for the individual woman, must be strictly differentiated from hypertrichosis, which is not androgendependent and occurs in both sexes, and also from the disease of virilization. The suffering derives from a divergence from the feminine ideal rather than from reality, and most forms of solitary hirsutism are probably to be assigned to the outer area of a Gaussian curve of sexual hair growth in normal women, by analogy to baldness in men. Although slightly elevated androgen levels are by no means rare, receptorial and postreceptorial processes in the hair follicle cells are at least of equal importance; both are modulated by a variety of partial factors. The salient point in workup is to exclude virilization and other primary diseases: this is usually possible on clinical grounds and by limited hormone measurements. Longterm therapy of solitary hirsutism is chiefly cosmetic, if there is no simultaneous wish for contraception. If this is desired, and if the hirsutism is mild, an initial low-dose cyproterone acetate-estrogen combination may be (appropriate. A higher dosage of cyproterone acetate Hammerstein 's regimen) over many years should be confined to severe forms.


Pretreatment with ibrutinib reduces cytokine secretion and limits the risk of obinutuzumab-induced infusion-related reactions in patients with CLL: analysis from the iLLUMINATE study.
Anti-CD20 antibody treatments, such as obinutuzumab, have been associated with infusion-related reactions (IRRs). In the phase 3 iLLUMINATE study of ibrutinib-obinutuzumab versus chlorambucil-obinutuzumab in first-line chronic lymphocytic leukemia/small lymphocytic lymphoma, IRRs were substantially reduced with ibrutinib-obinutuzumab versus chlorambucil-obinutuzumab. We prospectively analyzed inflammatory cytokines to evaluate the impact of ibrutinib on circulating cytokine levels following obinutuzumab infusion. In iLLUMINATE, ibrutinib or chlorambucil was given approximately 30-120 min before the first obinutuzumab infusion. Cytokines evaluated were IFNγ, IL-6, IL-8, IL-10, IL-18, MCP-1, MIP-1α, MIP-1β, and TNFα. Changes in peak cytokine levels from baseline (immediately before obinutuzumab) to post-obinutuzumab infusion were compared between arms and between patients with versus without IRRs using Wilcoxon rank sum test. Of 228 treated patients, 95 on ibrutinib-obinutuzumab (15 with IRRs, 80 without) and 88 on chlorambucil-obinutuzumab (45 with IRRs, 43 without) with cytokine data were included. Irrespective of IRR occurrence, median increase in cytokines was lower with ibrutinib-obinutuzumab versus chlorambucil-obinutuzumab for all cytokines (P < 0.01) except MIP-1β. Across treatment arms, post-obinutuzumab median increase in all cytokines except MIP-1β was greater in patients with versus without IRRs (P < 0.001). IL-6 and IL-8 elevations were associated with IRRs in both treatment arms. Among patients with IRRs, those receiving ibrutinib-obinutuzumab had lower post-obinutuzumab increases in IL-6, IL-8, IL-10, and MCP-1 (P < 0.04) than patients receiving chlorambucil-obinutuzumab. For patients in the ibrutinib-treatment arm, we observed a reduction in both the rate of clinically apparent IRRs and the levels of IRR-related cytokines and chemokines. This observation supports an immunomodulatory mechanism of action for ibrutinib. Clinical Trial Registration: NCT02264574.


Dynamic electrocardiography. III. The "imaginary cardiac vector" hypothesis: theoretical basis.
The "imaginary cardiac vector" hypothesis states that the "cardiac vector" is not a "real" vector entity. The hypothesis arises from the fact that voltage is not a vector but a scalar quantity. Nevertheless, in classical electrocardiographic analysis and teaching, the ECG voltage is treated as a vector. These voltages are used as "vector" components--first, to calculate a "resultant manifest potential difference", represented by the "cardiac vector" arrow in electrocardiography, and second, to draw the "cardiac vector" loop in vectorcardiography. The resultant "cardiac vector" is usually considered to be a "real" vector quantity describing the electrical activity of the heart. It is also widely believed that this "vector" was first described by Einthoven in 1913. To evaluate the hypothesis, we have utilised the actual values and methods presented by Einthoven, and demonstrated that the theoretical basis of the "cardiac vector" is false. It appears that Einthoven followed scalar and not vector procedures and that he did not describe a vector.


A typical antipsychotic treatment induced gradually expanding white matter alterations in healthy individuals with persistent auditory verbal hallucinations-an artificially controlled pilot study.
The aim of this study was to explore the effects of atypical antipsychotics (AaPs) on brain white matter (WM) tracts in healthy individuals with auditory verbal hallucinations (Hi-AVHs). We analyzed neuroimaging, AVH symptoms, and cognitive assessment data obtained from 39 Hi-AVHs who reported being distressed by persistent AVHs and volunteered to receive AaP treatment. We used tract-based spatial statistics (TBSS) and t tests to explore AaP pharmacotherapy effects on AVH symptoms and brain WM alterations in Hi-AVH subjects. TBSS and t tests revealed WM alterations after AaP treatment, relative to pretreatment observations. Although AaPs alleviated AVH symptoms, WM alterations in these subjects expanded over 8 months of AaP treatment, encompassing most major WM tracts by the end of the observation period, including the corpus callosum, arcuate fasciculus, cortico-spinal tracts, anterior commissure, and posterior commissure. The worsening of AaP-associated WM alterations observed in this study suggest that AaPs may not be a good choice for the treatment of Hi-AVHs despite their ability to alleviate AVHs.


Rotational error in path integration: encoding and execution errors in angle reproduction.
Path integration is fundamental to human navigation. When a navigator leaves home on a complex outbound path, they are able to keep track of their approximate position and orientation and return to their starting location on a direct homebound path. However, there are several sources of error during path integration. Previous research has focused almost exclusively on encoding error-the error in registering the outbound path in memory. Here, we also consider execution error-the error in the response, such as turning and walking a homebound trajectory. In two experiments conducted in ambulatory virtual environments, we examined the contribution of execution error to the rotational component of path integration using angle reproduction tasks. In the reproduction tasks, participants rotated once and then rotated again to face the original direction, either reproducing the initial turn or turning through the supplementary angle. One outstanding difficulty in disentangling encoding and execution error during a typical angle reproduction task is that as the encoding angle increases, so does the required response angle. In Experiment 1, we dissociated these two variables by asking participants to report each encoding angle using two different responses: by turning to walk on a path parallel to the initial facing direction in the same (reproduction) or opposite (supplementary angle) direction. In Experiment 2, participants reported the encoding angle by turning both rightward and leftward onto a path parallel to the initial facing direction, over a larger range of angles. The results suggest that execution error, not encoding error, is the predominant source of error in angular path integration. These findings also imply that the path integrator uses an intrinsic (action-scaled) rather than an extrinsic (objective) metric.


The role of radiation therapy in the management of skin cancers.
The use of radiation therapy in the management of skin cancer is variable and often anecdotal. Applied as both primary and adjuvant therapy in patients with both nonmelanoma skin cancer and rarer tumors of the skin, a consensus regarding optimal dosing regimens has not yet been reached. Herein, the authors outline the basic concepts of radiation therapy for tumors of the skin and review its use for high-risk nonmelanoma skin cancer, as well as less common malignancies, including angiosarcoma, Merkel cell carcinoma, and sebaceous carcinoma.


Fractures of the coronoid process.
Proper treatment of coronoid fractures requires an understanding of the bony and soft tissue anatomy of the elbow and the various injury mechanisms that occur. Newer fracture classifications help direct treatment based on the size and location of the fracture, injury mechanism, and associated stability of the elbow.


Choline kinase from yeast.
Choline kinase, the initial enzyme of the CDP-choline pathway, mediates the conversion of choline to phosphorylcholine and is localized in the supernatant fraction of cells. The enzyme also catalyzes the phosphorylation of ethanolamine, functioning as the initial enzyme of the CDP-ethanolamine pathway as well. Yeast choline kinase is encoded by a single structural gene, CKI, which was cloned by the genetic complementation of the choline kinase mutation cki. The deduced sequence comprises 582 amino acid residues with a molecular mass of 66316 Da and bears local sequence similarity to various protein kinases and bacterial antibiotic phosphotransferases. The expression of yeast choline kinase is transcriptionally repressed by myo-inositol and choline in a coordinate manner with other phospholipid-synthesizing enzymes in yeast.


Lingual lipase: an important lipase in the digestion of dietary lipids in cystic fibrosis?
A convenient lipase assay that discriminates between pancreatic and lingual lipase activities was developed to describe some properties of the triglyceride-hydrolyzing activities of lingual lipase (from von Ebners glands) and pancreatic lipase. Secretion of lingual lipase is stimulated by feeding. Gastric contents collected postyprandially from patients with cystic fibrosis (CF) contained lipase activity which is probably secreted from pharyngeal tissues. Also, duodenal contents from CF patients contained lipase activity with properties very close to those found in gastric contents from CF patients and controls. Apparently, the serous glands responsible for the secretion of lingual lipase is less affected than the exocrine pancrease in this disease. During fat balance experiments, CF patients utilized around 40% of the dietary lipids and more than 50% of milk lipids given as a test meal were hydrolyzed in the duodenum within 2 hr. In these patients with severe pancreatic insufficiency, we suggest that the lingual lipase is responsible for a considerable proportion of triglyceride hydrolysis. This hydrolysis starts in the stomach and continues in duodenum.


Structural and functional characterization of a novel molluskan ortholog of TRAF and TNF receptor-associated protein from disk abalone (Haliotis discus discus).
Immune signaling cascades have an indispensable role in the host defense of almost all the organisms. Tumor necrosis factor (TNF) signaling is considered as a prominent signaling pathway in vertebrate as well as invertebrate species. Within the signaling cascade, TNF receptor-associated factor (TRAF) and TNF receptor-associated protein (TTRAP) has been shown to have a crucial role in the modulation of immune signaling in animals. Here, we attempted to characterize a novel molluskan ortholog of TTRAP (AbTTRAP) from disk abalone (Haliotis discus discus) and analyzed its expression levels under pathogenic stress. The complete coding sequence of AbTTRAP consisted of 1071 nucleotides, coding for a 357 amino acid peptide, with a predicted molecular mass of 40 kDa. According to our in-silico analysis, AbTTRAP resembled the typical TTRAP domain architecture, including a 5'-tyrosyl DNA phosphodiesterase domain. Moreover, phylogenetic analysis revealed its common ancestral invertebrate origin, where AbTTRAP was clustered with molluskan counterparts. Quantitative real time PCR showed universally distributed expression of AbTTRAP in selected tissues of abalone, from which more prominent expression was detected in hemocytes. Upon stimulation with two pathogen-derived mitogens, lipopolysaccharide (LPS) and polyinosinic:polycytidylic acid (poly I:C), transcript levels of AbTTRAP in hemocytes and gill tissues were differentially modulated with time. In addition, the recombinant protein of AbTTRAP exhibited prominent endonuclease activity against abalone genomic DNA, which was enhanced by the presence of Mg(2+) in the medium. Collectively, these results reinforce the existence of the TNF signaling cascade in mollusks like disk abalone, further implicating the putative regulatory behavior of TTRAP in invertebrate host pathology.


Can bioimpedance cardiography assess hemodynamic response to passive leg raising in critically ill patients: A STROBE-compliant study.
Passive leg raising (PLR) is a convenient and reliable test to predict fluid responsiveness. The ability of thoracic electrical bioimpedance cardiography (TEB) to monitor changes of cardiac output (CO) during PLR is unknown.In the present study, we measured CO in 61 patients with shock or dyspnea by TEB and transthoracic echocardiography (TTE) during PLR procedure. Positive PLR responsiveness was defined as the velocity-time integral (VTI) ≥10% after PLR. TTE measured VTI in the left ventricular output tract. The predictive value of TEB parameters in PLR responders was tested. Furthermore, the agreement of absolute CO values between TEB and TTE measurements was assessed.Among the 61 patients, there were 28 PLR-responders and 33 non-responders. Twenty-seven patients were diagnosed with shock and 34 patients with dyspnea, with 55.6% (15/27) and 54.6% (18/34) non-responders, respectively. A change in TEB measured CO (ΔCO) ≥9.8% predicted PLR responders with 75.0% sensitivity and 78.8% specificity, the area under the receiver operating characteristic curve (AUROC) was 0.79. The Δd2Z/dt2 (a secondary derivative of the impedance wave) showed the best predictive value with AUROC of 0.90, the optimal cut point was -7.1% with 85.7% sensitivity and 87.9% specificity. Bias between TEB and TTE measured CO was 0.12 L/min, and the percentage error was 65.8%.TEB parameters had promising performance in predicting PLR responders, and the Δd2Z/dt2 had the best predictive value. The CO values measured by TEB were not interchangeable with TTE in critically ill settings.


A rare entity of bilateral hutch diverticulum asymptomatic in adult revealed during the assessment of hematuria.
Hutch diverticulum is a rare congenital entity that develops in the ureteral hiatus or in its proximity and is accompanied by reflux in most cases. There are very few reported cases and most of them are in children and predominately at solitary side. Adult cases are rare. We review the literature and present a case of a 65-year-old man with bilateral hutch diverticulum asymptomatic revealed during assessment of hematuria.


Thiophenyl-substituted triazolyl-thione L-alanine: asymmetric synthesis, aggregation and biological properties.
In this work, we report the asymmetric synthesis and characterization of an artificial amino acid based on triazolyl-thione L-alanine, which was modified with a thiophenyl-substituted moiety, as well as in vitro studies of its nucleic acid-binding ability. We found, by dynamic light scattering studies, that the synthetic amino acid was able to form supramolecular aggregates having a hydrodynamic diameter higher than 200 nm. Furthermore, we demonstrated, by UV and CD experiments, that the heteroaromatic amino acid, whose enzymatic stability was demonstrated by HPLC analysis also after 24 h of incubation in human serum, was able to bind a RNA complex, which is a feature of biomedical interest in view of innovative antiviral strategies based on modulation of RNA-RNA molecular recognition.