Echocardiographic assessment of regional right ventricular function: a head-to-head comparison between 2-dimensional and tissue Doppler-derived strain analysis.
We sought to compare the feasibility and results of Doppler tissue imaging-derived and 2-dimensional strain echocardiography-derived deformation assessment of the right ventricular (RV) free wall. Absolute values and timing of strain and strain rate (SR) obtained by both techniques in the basal, mid, and apical segments of the RV free wall were prospectively analyzed and compared in individuals with varying RV function and geometry: patients with an impaired RV function (n = 23), endurance athletes (n = 22), and control subjects (n = 22). Both techniques yielded a 93% technical feasibility and had a similar interobserver and intraobserver variability. The overall correlation for onset strain values was 0.59, with better correlation in the pathologic RV (r = 0.77). The overall correlation of peak strain was moderately good for strain values (r = 0.73) and timing (r = 0.56). Over the entire range of systolic and diastolic values, SR correlated closely (r = 0.90). Systolic SR correlated moderately (r = 0.59), but its timing poorly (r = 0.35). There was a small bias toward higher values of strain and SR when using Doppler tissue imaging, except in the basal segment. Overall, in the assessment of RV deformation, Doppler tissue imaging and 2-dimensional strain echocardiography correlate moderately well and display a comparable feasibility.


Protein Function Prediction.
Protein function is a concept that can have different interpretations in different biological contexts, and the number and diversity of novel proteins identified by large-scale "omics" technologies poses increasingly new challenges. In this review we explore current strategies used to predict protein function focused on high-throughput sequence analysis, as for example, inference based on sequence similarity, sequence composition, structure, and protein-protein interaction. Various prediction strategies are discussed together with illustrative workflows highlighting the use of some benchmark tools and knowledge bases in the field.


Ultrathin endoscopy in the assessment and treatment of upper and lower gastrointestinal tract strictures.
Ultrathin (</= 6 mm diameter) endoscopes have recently been introduced into clinical practice. We retrospectively assessed the role of a 6 mm diameter videoendoscope in 15 patients with tight gastrointestinal tract strictures. The ultrathin endoscope was successfully passed through 9 of 12 esophageal strictures not amenable to endoscopy with a standard-diameter endoscope allowing stricture dilatation or nasogastric tube placement in 8 of these. Ultrathin endoscopy was also successful in passing 3 lower gastrointestinal tract strictures caused by Crohn's disease that were impassable using larger-diameter endoscopes. Ultrathin endoscopy is potentially useful in the assessment and treatment of some upper and lower gastrointestinal tract strictures.


Frontotemporal dementia: clinical, neuroimaging, and molecular biological findings in 6 patients.
Establishing the diagnosis in patients with clinical signs and symptoms suggesting primary degenerative disease with marked frontal lobe involvement is difficult. Neuroimaging methods, in particular positron emission tomography (PET) with the tracer 18fluoro-2-deoxyglucose (FDG) and cerebrospinal fluid (CSF) examination of beta-amyloid and tau-protein levels may give additional information. We report five patients with clinical and radiological features of degenerative dementia with predominantly frontal involvement and one patient with primary progressive aphasia Diagnostic work-up included computed tomography (CT), magnetic resonance imaging (MRI), PET and tau-protein and beta-amyloid level determination in CSF. While neuropsychological performance varied among patients, CT and MRI demonstrated persistently frontal lobe involvement. PET revealed corresponding changes with frontal hypometabolism, but in addition, four patients (among them two with no corresponding temporal changes in CT or MRI) showed a decreased glucose uptake in the temporal cortices. CSF samples from five patients revealed elevated beta-amyloid 1-42 and tau levels in three and two patients, respectively. Reduced beta-amyloid 1-40 was found in two patients. We conclude that occurrence of clinical symptoms of frontotemporal dementia is accompanied by frontal hypometabolism regardless of additional clinical findings. The value of determination of beta-amyloid and tau protein levels remains to be determined.


Presence of crystalline lens as a protective factor for the late development of open angle glaucoma after vitrectomy.
To evaluate the late development of open angle glaucoma (OAG) after vitrectomy and to compare the rate of postvitrectomy OAG development in phakic and pseudophakic eyes. Retrospective case series of 101 eyes of 101 patients who had vitrectomy for idiopathic epiretinal membrane or idiopathic macular hole with a follow-up duration of more than 6 months. Eligible patients were assessed for new development of OAG during the follow-up period. Patients were separated into two groups based on the lens status at the end of the vitrectomy for statistical analysis using Kaplan-Meier survival analysis with log-rank test and Cox regression analysis. The mean follow-up duration was 51 months (range, 6-80 months). Of the 101 eyes, 8 (7.9%) eyes developed OAG during the follow-up period. Phakic eyes were less likely to develop OAG after vitrectomy compared with pseudophakic eyes, with 2% and 13%, respectively (log-rank test, P = 0.025). The result remained statistically significant after adjustment for age, refractive error and the use of gas tamponade (adjusted odds ratio = 0.09, P = 0.038). The presence of the crystalline lens may be protective against the late development of OAG after vitrectomy.


Mammary uptake of fatty acids supplied by intravenous triacylglycerol infusion to lactating dairy cows.
Supplementing dairy cows with n-3 fatty acid-rich feeds does not easily increase quantities in milk fat. Previous results demonstrated very long-chain n-3 fatty acids are primarily transported in the PL fraction of blood, making them largely unavailable to the mammary gland for enrichment of milk fat. Our objective was to compare mammary uptake of fatty acids of increasing chain length and unsaturation delivered intravenously as TAG emulsions. Late lactation dairy cows were assigned to a completely randomized block design. Treatments were intravenous TAG emulsions enriched with oleic acid (OLA), linoleic acid (LNA), alpha-linolenic acid (ALA), or docosahexaenoic acid (DHA) and were delivered continuously at 16 mL/h for 72 h. Each treatment supplied 30 g/day of the target fatty acid. Treatment did not affect feed intake, milk yield, or milk composition, but all treatments reduced intake and yield. The proportion of DHA increased in plasma FFA, TAG, and PL with infusion. Increases of n-3 fatty acids, ALA, EPA, and DHA, were evident in the plasma PL fraction, suggesting re-esterification in the liver. Transfer efficiencies were 37.8 ± 4.1, 27.6 ± 5.4, and 10.9 ± 4.1 %, and day 3 total milk fatty acyl yields were 37.0 ± 3.4, 10.8 ± 0.4, and 3.3 ± 0.3 g for LNA, ALA, and DHA. Variation in oleic acyl yield prevented calculation of OLA transfer efficiency. Mammary uptake of fatty acids was reduced with increased chain length and unsaturation. Both liver and mammary mechanisms may regulate transfer of long-chain polyunsaturates.


Reverberation of recent visual experience in spontaneous cortical waves.
Spontaneous waves of activity propagating across large cortical areas may play important roles in sensory processing and circuit refinement. However, whether these waves are in turn shaped by sensory experience remains unclear. Here we report that visually evoked cortical activity reverberates in subsequent spontaneous waves. Voltage-sensitive dye imaging in rat visual cortex shows that following repetitive presentation of a given visual stimulus, spatiotemporal activity patterns resembling the evoked response appear more frequently in the spontaneous waves. This effect is specific to the response pattern evoked by the repeated stimulus, and it persists for several minutes without further visual stimulation. Such wave-mediated reverberation could contribute to short-term memory and help to consolidate the transient effects of recent sensory experience into long-lasting cortical modifications.


Postexposure-vaccine-prophylaxis against COVID-19.
During the COVID-19 pandemic, postexposure-vaccine-prophylaxis is not a practice. Following exposure, only patient isolation is imposed. Moreover, no therapeutic prevention approach is applied. We asked whether evidence exists for reduced mortality rate following postexposure-vaccine-prophylaxis. To estimate the effectiveness of postexposure-vaccine-prophylaxis, we obtained data from the Israeli Ministry of Health registry. The study population consisted of Israeli residents aged 12 years and older, identified for the first time as PCR-positive for SARS-CoV-2, between December 20th, 2020 (the beginning of the vaccination campaign) and October 7th, 2021. We compared "recently injected" patients-that proved PCR-positive on the same day or on 1 of the 5 consecutive days after first vaccination (representing an unintended postexposure-vaccine-prophylaxis)s-to unvaccinated control group. Among Israeli residents identified PCR-positive for SARS-CoV-2, 11 687 were found positive on the day they received their first vaccine injection (BNT162b2) or on 1 of the 5 days thereafter. In patients over 65 years, 143 deaths occurred among 1412 recently injected (10.13%) compared to 255 deaths among the 1412 unvaccinated (18.06%), odd ratio (OR) 0.51 (95% confidence interval [CI]: 0.41-0.64; p < 0.001). A significant reduction in the death toll was observed among the 55-64 age group, with 8 deaths occurring among the 1320 recently injected (0.61%) compared to 24 deaths among the 1320 unvaccinated control (1.82%), OR 0.33 (95% CI: 0.13-0.76; p = 0.007). Postexposure-vaccine-prophylaxis is effective against death in COVID-19 infection.


4-hydroxynonenal and neurodegenerative diseases.
The development of oxidative stress, in which production of highly reactive oxygen species (ROS) overwhelms antioxidant defenses, is a feature of many neurological diseases: ischemic, inflammatory, metabolic and degenerative. Oxidative stress is increasingly implicated in a number of neurodegenerative disorders characterized by abnormal filament accumulation or deposition of abnormal forms of specific proteins in affected neurons, like Alzheimer's disease (AD), Pick's disease, Lewy bodies related diseases, amyotrophic lateral sclerosis (ALS), and Huntington disease. Causes of neuronal death in neurodegenerative diseases are multifactorial. In some familiar cases of ALS mutation in the gene for Cu/Zn superoxide dismutase (SOD1) can be identified. In other neurodegenerative diseases ROS have some, usually not clear, role in early pathogenesis or implications on neuronal death in advanced stages of illness. The effects of oxidative stress on "post-mitotic cells", such as neurons may be cumulative, hence, it is often unclear whether oxidative damage is a cause or consequence of neurodegeneration. Peroxidation of cellular membrane lipids, or circulating lipoprotein molecules generates highly reactive aldehydes among which one of most important is 4-hydroxynonenal (HNE). The presence of HNE is increased in brain tissue and cerebrospinal fluid of AD patients, and in spinal cord of ALS patients. Immunohistochemical studies show presence of HNE in neurofibrilary tangles and in senile plaques in AD, in the cytoplasm of the residual motor neurons in sporadic ALS, in Lewy bodies in neocortical and brain stem neurons in Parkinson's disease (PD) and in diffuse Lewy bodies disease (DLBD). Thus, increased levels of HNE in neurodegenerative disorders and immunohistochemical distribution of HNE in brain tissue indicate pathophysiological role of oxidative stress in these diseases, and especially HNE in formation of abnormal filament deposites.


The impact of periodontal treatment on healthcare costs in newly diagnosed diabetes patients: Evidence from a German claims database.
There is sufficient scientific evidence for the bidirectional association between periodontal diseases and diabetes. In this context, we hypothesized that periodontal treatment leads to lower healthcare costs in newly diagnosed diabetes patients by promoting a milder disease course. A total of 23,771 persons were investigated who were continuously insured by German health insurances between 2011 and 2016, 18 years or older, and newly diagnosed with diabetes in 2013. The study population was divided into a periodontal treatment and control group (no periodontal treatment). The average treatment effect of a periodontal treatment on various types of healthcare costs (inpatient, outpatient, drug costs) was analyzed by a doubly robust method. Finally, 5.3% of the study population could be assigned to the treatment group. In newly diagnosed diabetes patients with periodontal treatment, a reduction in total healthcare costs (0.96, 95%CI 0.89; 1.04), inpatient costs (0.87, 95%CI 0.69; 1.08), diabetes-related drug costs (0.93, 95%CI 0.84; 1.03) and other drug costs (0.97, 95%CI 0.89; 1.05) could be shown compared to the control group. This study provides evidence that periodontal treatment for diabetes patients reduces healthcare costs. Fewer diabetes-specific complications and hospitalizations are expected.


Creating experimental analogs with available clinical information: credible alternatives to "gold-standard" experiments?
Comparison of the implementation and findings of a "gold standard" evaluation of social work intervention and its experimental analog based on available clinical information illustrates the strengths and weaknesses of each. From a practice-research integration perspective, however, "clinical data-mining" may be a credible alternative to randomized controlled experiments.


Development of metal-ion containing catalysts for the decomposition of phosphorothioate esters.
The widespread use of phosphorothioate esters as agricultural pesticides, chemical weapons and mechanistic probes in enzymology has sparked interest in the reactivity of these thio-substituted analogues of phosphate esters. In this brief account, we summarize the recent developments in our understanding of the mechanisms of hydrolysis (and solvolysis in methanol) of phosphorothioates containing a sulfur atom in the bridging and/or non-bridging position. A small number of highly efficient catalytic systems containing the metal ions La(III), Pd(II), Cu(II) and Zn(II) have been developed to promote the degradation of the various classes of phosphorothioate esters. The mechanisms of the base promoted solvolytic reactions in water and methanol and those of the metal catalyzed cleavage are presented, as well as a discussion of the energetics of the catalytic processes and other salient features. The aim of this review is to provide the reader with a contemporary physical organic description of phosphorothioate ester cleavage. This article is part of a Special Issue entitled: Chemistry and mechanism of phosphatases, diesterases and triesterases.


Use of Implantable Cardioverter-Defibrillators for Primary Prevention of Sudden Cardiac Death in Asia.
The effectiveness of primary prevention implantable cardioverter-defibrillators (ICDs) is well established. However, there are several unsolved problems related to ICD use for primary prevention in Asia, including ICD underuse, population differences in underlying heart disease, and the rate of appropriate ICD therapy compared with Western countries. Although the prevalence of ischemic cardiomyopathy in Asia is lower than in Europe and the United States, the mortality rate of Asian patients with ischemic heart disease has been increasing recently. As for the use of ICDs for primary prevention, there have been no randomized clinical trials, and limited data are available in Asia. This review focuses on the unmet needs related to ICD use for primary prevention in Asia.


Role of SELENBP1 and SELENOF in prostate cancer bioenergetics.
The contribution of selenium and selenoproteins in prostate cancer etiology remains elusive, potentially due to insufficient information regarding the biochemical pathways in which they are involved. There are twenty-five human selenocysteine-containing proteins or selenoproteins as well as a smaller class of selenium-containing proteins that do not include selenocysteine, and their cancer-associated aberrations, both genetic and functional, have evoked special interest, although their contribution to the metabolic reprogramming of prostate cancers remains has not been extensively studied. While benign prostate tissue exhibits a glycolytic phenotype, neoplastic events restore the truncated tricarboxylic acid cycle and enhance oxidative phosphorylation. Two selenium-containing proteins, selenium binding protein 1 and selenoprotein F, affect prostate cancer phenotypes by modulating tumor cell metabolic profiles with significant effects on mitochondrial biology, including oxidative phosphorylation and ATP synthesis. One of the pathways affected by both proteins is the activation of adenosine monophosphate kinase and its downstream signaling with concomitant induction of glycolysis. This review focuses on highlighting the role of these two proteins in modulating the bioenergetic profile of prostate cancer and in maintaining the metabolic plasticity of these cells rendering growth advantage and possible therapeutic resistance.


Edaphic control of habitat selection by kangaroo mice (Microdipodops) in three Nevadan populations.
The influence of soil texture on habitat selection by kangaroo mice was evaluted at three areas - Lincoln, Nye, and Pershing Counties, Nevada, where Microdipodops megacephalus and M. pallidus are sympatric.All rodents captured on surveyed grids were marked by toe-clipping and released where they were caught. Soils were sampled chiefly at the positions of traps which had captured kangaroo mice. A soil was classified as sand if 95% (by weight) or more of a sample passed a 2.00-mm sieve, and as gravel if less material passed the sieve. In the areas investigated, a Sarcobatus baileyi-Atriplex confertifolia community predominated.Capture-recapture data from the three study areas were both evaluted individually for each plot and pooled. Although the distribution of M. pallidus was shown to be random with regard to soil type, M. megacephalus was captured almost exclusively on gravel. Comparison of the species using pooled data showed a highly significant difference (p=0.001) in the types of soil on which they were captured. Theoretical implications of the study are discussed.


One-year increase of Coll 2-1, a new marker of type II collagen degradation, in urine is highly predictive of radiological OA progression.
To analyse the relationship between the levels of urinary biochemical markers of type II collagen degradation and the clinical and radiological severity and progression of knee osteoarthritis (OA). Seventy-five patients with primary knee OA were included in this 3-year follow-up study. Mean joint space width (JSW) of the medial compartment of the femorotibial joint was measured with a computer assisted method on standardized radiographs taken at baseline and after a 3-year follow-up. Pain, stiffness, and physical function subscales of the Western Ontario and McMaster Universities (WOMAC) were assessed at the same time points. Type II collagen peptides Coll 2-1 and Coll 2-1 NO(2), as well as pyridinoline (Pyr) and deoxypyridinoline (D-Pyr) were measured in urines at baseline, after 1 year and 3 years, with specific immunoassays. At baseline, significant correlations were found between the urinary Coll 2-1 and Coll 2-1 NO(2) levels and the global WOMAC score (Coll 2-1: r=0.28, P=0.01; Coll 2-1 NO(2): r=0.27, P=0.02) and its subscales for pain (Coll 2-1: r=0.27, P=0.01; Coll 2-1 NO(2): r=0.30, P=0.01) and function (Coll 2-1: r=0.29, P=0.01; Coll 2-1 NO(2): r=0.27, P=0.02). Pyr and D-Pyr levels were not significantly correlated with the WOMAC scores. One-year change in Coll 2-1 and Coll 2-1 NO(2) urinary levels were negatively correlated with a 3-year change in JSW (Coll 2-1: r=-0.31, P=0.03; Coll 2-1 NO(2): r=-0.31, P=0.03), indicating that an increase of Coll 2-1 or Coll 2-1 NO(2) over 1 year is predictive of subsequent joint space narrowing. Neither Pyr nor D-Pyr was correlated with radiological OA progression. At baseline, Coll 2-1 and Coll 2-1 NO(2) urinary levels were indicative of the clinical activity of knee OA and the increase of these peptides over 1 year was predictive of the radiological progression of knee OA.


Oxidative Damage of Proteins Precedes Loss of Cholinergic Phenotype in the Septal Neurons of Olfactory Bulbectomized Mice.
The development of cholinergic deficit is considered an early sign of a number of pathological conditions, including Alzheimer's disease. Cholinergic dysfunction underlies cognitive decline associated with both normal aging and Alzheimer's disease. Here, we studied a possible mechanism of functional impairment of cholinergic neurons using an olfactory bulbectomy model. Male mice were subjected to olfactory bulbectomy or sham surgery. Three weeks after that they were trained in Morris water maze and then euthanized one month after surgery. The cholinergic indices as well as the indices of oxidative stress were studied using immunohistochemistry, western blot and ELISA. Gene expression was studied using RT-qPCR. The experimental treatment was followed by impaired learning of a standard spatial task in a water maze. This was associated with a decrease in the number of cells containing choline acetyltransferase (ChAT), in relation to total number of neurons in the medial septum and lower ChAT enzymatic activity in the hippocampus. However, the levels of mRNAs of ChAT, vesicular ACh transporter and acetylcholine esterase remained unchanged in bulbectomized mice compared to sham-operated animals. These alterations were preceded by the accumulation of protein-bound carbonyls, indicating oxidative damage of proteins, whereas oxidative damage of nucleic acids was not detected. We assume that in olfactory bulbectomy model, oxidative damage of proteins may cause cholinergic dysfunction rather than irreversible neuronal damage. These data indicate that cholinergic neurons of the basal forebrain are very sensitive to oxidative stress, which may be responsible for the appearance of early cognitive decline in Alzheimer's disease.


On the axisymmetric stability of heated supersonic round jets.
We perform an inviscid, spatial stability analysis of supersonic, heated round jets with the mean properties assumed uniform on either side of the jet shear layer, modelled here via a cylindrical vortex sheet. Apart from the hydrodynamic Kelvin-Helmholtz (K-H) wave, the spatial growth rates of the acoustically coupled supersonic and subsonic instability waves are computed for axisymmetric conditions (m=0) to analyse their role on the jet stability, under increased heating and compressibility. With the ambient stationary, supersonic instability waves may exist for any jet Mach number Mj ≥2, whereas the subsonic instability waves, in addition, require the core-to-ambient flow temperature ratio Tj /To >1. We show, for moderately heated jets at Tj /To >2, the acoustically coupled instability modes, once cut on, to govern the overall jet stability with the K-H wave having disappeared into the cluster of acoustic modes. Sufficiently high heating makes the subsonic modes dominate the jet near-field dynamics, whereas the supersonic instability modes form the primary Mach radiation at far field.


Changes in plasma carotenoid and vitamin E profile during supplementation with oil palm fruit carotenoids.
It has been hypothesized that supplementation with a single source of carotenoids causes perturbations in the plasma level of diet-derived carotenoids and that this may explain the lack of association between disease rates and the intake of carotenoid supplements. This article describes the effect of supplementation with an oil palm fruit extract, rich in beta-and alpha-carotene, on the plasma carotenoid profile of 15 healthy women volunteers. Volunteers were supplemented for 35 days with 15 mg/d of total carotenoids. Blood samples were taken at regular intervals during the supplementation period and analyzed for a range of carotenoids. Results indicate that the hydrocarbon carotenoid components of the supplement are absorbed and appear in the plasma disproportionately to the ratios in the supplement and that the plasma concentration of diet-derived lutein, a dihydroxy carotenoid ((3R,3S,6R)-beta,epsilon-carotene-3,3-diol), is depressed, whereas that of lycopene is unaffected. Plasma alpha-tocopherol concentrations were unaffected by supplementation. It is concluded that supplementation with carotenoids from a single source results in plasma carotenoid profile changes that are not predictable from a knowledge of supplement composition and that such changes should be monitored and considered when drawing conclusions as to the effect of carotenoid supplementation on health outcomes.


CT of emphysematous gastritis.
Emphysematous gastritis is a serious, often fatal condition. It is the result of destruction of the mucosal membrane with subsequent bacterial invasion of the stomach. We have encountered two cases at CT. Recognition is important since early intervention may be lifesaving.


Effects of hemicholinium-3 or physostigmine on rat brain noradrenaline depletion induced by foot shocks.
Foot shocks applied to the rat on a grid floor caused brain noradrenaline depletion. Hemicholinium-3 injected intracerebroventricularly (i.c.v.) blocked the noradrenaline depletion and this blockade was reversed by choline (i.c.v.). Physostigmine (i.c.v.) had different effects according to the age of the rats: "young" and "intermediate" groups were depleted but not "adult" groups. Physostigmine plus shocks caused depletion only in "young" groups; the depletion not shown in "intermediat" groups, reappeared after pretreatment with alpha-methyl-p-tyrosine. It is concluded that there probably is a relationship between cholinergic and adrenergic neural systems when brain noradrenaline id depleted by shocks.


Application of a new tandem isomerization-aldolization reaction of allylic alcohols to the synthesis of three diastereoisomers of (2R)-1,2-O-isopropylidene-4-methylpentane-1,2,3,5-tetraol.
The tandem isomerization-aldolization reaction of (2R)-1,2-O-isopropylidene-4-penten-1,2,3-triol 3 and formaldehyde gives a mixture of two aldol products 2a and 2b. The stereoselective reduction of each compound by l-Selectride affords two diastereoisomers of (2R)-1,2-O-Isopropylidene-4-methylpentane-1,2,3,5-tetraol while a third diastereoisomer is obtained by stereoselective reduction with Me(4)NHB(OAc)(3).


Evolution of bubbles from gas micronuclei formed on the luminal aspect of ovine large blood vessels.
It has been shown that tiny gas nanobubbles form spontaneously on a smooth hydrophobic surface submerged in water. These nanobubbles were shown to be the source of gas micronuclei from which bubbles evolved during decompression of silicon wafers. We suggest that the hydrophobic inner surface of blood vessels may be a site of nanobubble production. Sections from the right and left atria, pulmonary artery and vein, aorta, and superior vena cava of sheep (n=6) were gently stretched on microscope slides and exposed to 1013 kPa for 18 h. Hydrophobicity was checked in the six blood vessels by advancing contact angle with a drop of saline of 71±19°, with a maximum of about 110±7° (mean±SD). Tiny bubbles ~30 μm in diameter rose vertically from the blood vessels and grew on the surface of the saline, where they were photographed. All of the blood vessels produced bubbles over a period of 80 min. The number of bubbles produced from a square cm was: in the aorta, 20.5; left atrium, 27.3; pulmonary artery, 17.9; pulmonary vein, 24.3; right atrium, 29.5; superior vena cava, 36.4. More than half of the bubbles were present for less than 2 min, but some remained on the saline-air interface for as long as 18 min. Nucleation was evident in both the venous (superior vena cava, pulmonary artery, right atrium) and arterial (aorta, pulmonary vein, left atrium) blood vessels. This newly suggested mechanism of nucleation may be the main mechanism underlying bubble formation on decompression.


Safety and efficacy of periurethral constrictor implantation for the treatment of post-radical prostatectomy incontinence.
To assess safety and efficacy of the periurethral constrictor for the treatment of postprostatectomy urinary incontinence. Periurethral constrictor is a minimally invasive, low-cost (€ 2000) device based on an adjustable occlusive mechanism. From December 2004 to March 2010 the device was implanted in 66 patients with mild to severe incontinence (3 or more pads per day) through a 3- to 5-cm perineal incision. Median surgical time was 35 minutes (range 25-60). Discharge occurred on day 1 after removing the indwelling urethral catheter. In 4 cases (6%), the device was removed because of infection/periurethral erosion. At 18 months, 62 patients were valuable; continence was recovered totally in 49 cases (79%), partially in 9 (15%) cases, and remained unchanged in 4 (6%). No one needed self-catheterization to empty the bladder. Periurethral constrictor improved continence in most of the patients. Nevertheless, a larger series and longer follow-up are needed to confirm safety and to test durability.


Role of adjunctive posterior wall isolation in patients undergoing atrial fibrillation ablation: a systematic review and meta-analysis.
The posterior wall of the left atrium may promote atrial fibrillation (AF) due to its propensity for fibrosis, in addition to a high prevalence of non-pulmonary vein triggers. Multiple smaller studies have assessed the incremental value of posterior wall isolation (PWI) in addition to standard atrial fibrillation. Similarly, this method has shown promise as an ablation strategy for patients with persistent AF, when PVI alone has shown only modest efficacy. We performed an extensive literature search and systematic review of studies that compared AF ablation plus PWI versus control. We separately assessed the recurrence rates of all atrial arrhythmias (AF/AFL/AT), as well as separate recurrence rates of AF and atrial tachycardia/atrial flutter (AT/AFL) after ablation. Risk ratio (RR) 95% confidence intervals were measured using the Mantel-Haenszel method. The random effects model was used due to heterogeneity (I2) > 25%. Seven studies with a total of 1151 patients were included. Patients who underwent concomitant PWI experienced less recurrence of all atrial arrhythmias post ablation (RR 0.77; 95% CI 0.62-0.96, p = 0.02) and less recurrence of AF (RR 0.55; 95% CI 0.39-0.77, p < 0.01). There was no difference in onset of AT/AFL (RR 0.96; 95% CI 0.62-1.48, p = 0.85) after ablation. These results were replicated in subgroup analysis of patients with persistent AF. Based on the results of this meta-analysis, concomitant PWI is associated with less recurrence of AF and all atrial arrhythmias after ablation, without an increase in the risk for post-ablation AFL/AT.


A new paradigm for Aedes spp. surveillance using gravid ovipositing sticky trap and NS1 antigen test kit.
Dengue remains a serious public health problem in Southeast Asia and has increased 37-fold in Malaysia compared to decades ago. New strategies are urgently needed for early detection and control of dengue epidemics. We conducted a two year study in a high human density dengue-endemic urban area in Selangor, where Gravid Ovipositing Sticky (GOS) traps were set up to capture adult Aedes spp. mosquitoes. All Aedes mosquitoes were tested using the NS1 dengue antigen test kit. All dengue cases from the study site notified to the State Health Department were recorded. Weekly microclimatic temperature, relative humidity (RH) and rainfall were monitored. Aedes aegypti was the predominant mosquito (95.6%) caught in GOS traps and 23% (43/187 pools of 5 mosquitoes each) were found to be positive for dengue using the NS1 antigen kit. Confirmed cases of dengue were observed with a lag of one week after positive Ae. aegypti were detected. Aedes aegypti density as analysed by distributed lag non-linear models, will increase lag of 2-3 weeks for temperature increase from 28 to 30 °C; and lag of three weeks for increased rainfall. Proactive strategy is needed for dengue vector surveillance programme. One method would be to use the GOS trap which is simple to setup, cost effective (below USD 1 per trap) and environmental friendly (i.e. use recyclable plastic materials) to capture Ae. aegypti followed by a rapid method of detecting of dengue virus using the NS1 dengue antigen kit. Control measures should be initiated when positive mosquitoes are detected.


Annotated dataset creation through large language models for non-english medical NLP.
Obtaining text datasets with semantic annotations is an effortful process, yet crucial for supervised training in natural language processing (NLP). In general, developing and applying new NLP pipelines in domain-specific contexts for tasks often requires custom-designed datasets to address NLP tasks in a supervised machine learning fashion. When operating in non-English languages for medical data processing, this exposes several minor and major, interconnected problems such as the lack of task-matching datasets as well as task-specific pre-trained models. In our work, we suggest to leverage pre-trained large language models for training data acquisition in order to retrieve sufficiently large datasets for training smaller and more efficient models for use-case-specific tasks. To demonstrate the effectiveness of your approach, we create a custom dataset that we use to train a medical NER model for German texts, GPTNERMED, yet our method remains language-independent in principle. Our obtained dataset as well as our pre-trained models are publicly available at https://github.com/frankkramer-lab/GPTNERMED.


Challenges in the adoption of new pharmacotherapeutics for addiction to alcohol and other drugs.
The adoption of pharmacotherapies for the treatment of alcohol and drug use disorders has progressed slowly despite the approval of new and effective medications. This paper begins with overviews of the prevalence of alcohol and drug abuse and dependence, the costs of addiction to the nation, and the value of treatment services. The role of pharmacotherapy in the treatment of addictive diseases is examined, and factors that affect the adoption and use of medications for alcohol and drug treatment are identified and discussed. Investigations that tested the effectiveness of buprenorphine for treatment of opioid dependence in new settings illustrate physician and counselor training and mentorship strategies that may promote the adoption of medications in the treatment of alcohol and drug use disorders. The paper concludes with a discussion of barriers and ways to surmount the barriers and to foster greater use of medications in alcohol and drug treatment.


Racial/Ethnic and poverty disparities in human papillomavirus vaccination completion.
Two vaccines against human papillomavirus (HPV), a necessary cause of cervical cancer, are currently licensed and recommended for routine administration in the U.S. to girls in a three-dose series. This study examined effects of race/ethnicity, poverty, and year on completion of the three-dose HPV vaccine series among those who initiated vaccination. Data from the 2008-2009 National Immunization Survey-Teen for girls aged 13-17 years who received at least one dose of HPV vaccine (n=7606) were analyzed in 2010-2011 using logistic regression to adjust for covariates including measures of access to care. During this 2-year period, 55% of adolescent girls who initiated vaccination completed the three-dose series. Completion was significantly higher in 2009 (60%) compared to 2008 (48%; p<0.001). After controlling for covariates, adolescents who were black (AOR=0.48, 95% CI=0.40, 0.57) or Hispanic (AOR=0.75, 95% CI=0.64, 0.88) were significantly less likely to complete vaccination than whites. Adolescents living below the federal poverty level were significantly less likely to complete vaccination than adolescents with household incomes >$75,000 (AOR=0.76, 95% CI=0.63, 0.92). There was no significant interaction between race/ethnicity and year (p=0.92). Although poverty was associated with lower completion rates in 2008, this association was not observed in 2009 (p<0.05 for poverty-year interaction). HPV vaccination completion rates increased between 2008 and 2009. However, significant differences by race/ethnicity and poverty were observed, and the racial/ethnic differences persisted.


A High-Throughput Absolute Quantification of Protein-Bound Sulfur Amino Acids from Model and Crop Plant Seeds.
In this procedure, we describe a high-throughput absolute quantification protocol for the protein-bound sulfur amino acids, cysteine (Cys) and methionine (Met), from plant seeds. This procedure consists of performic acid oxidation that transforms bound Cys into cysteic acid (CysA) and bound Met into methionine sulfone (MetS) followed by acid hydrolysis. The absolute quantification step is performed by multiple reaction monitoring tandem mass spectrometry (LC-MS/MS). The approach facilitates the analysis of a few hundred samples per week by using a 96-well plate extraction setup. Importantly, the method uses only ∼4 mg of tissue per sample and uses the common acid hydrolysis protocol, followed by water extraction that includes DL-Ser-d3 and L-Met-d3 as internal standards to enable the quantification of the absolute levels of the protein-bound Cys and Met with high precision, accuracy, and reproducibility. The protocol described herein has been optimized for seed samples from Arabidopsis thaliana, Glycine max, and Zea mays but could be applied to other plant tissues. © 2023 Wiley Periodicals LLC. Basic Protocol: Analysis of protein-bound cysteine and methionine from seeds.


Fatal clostridial sepsis after spontaneous abortion.
Although obstetric mortality due to complications of Clostridium perfringens infection is rare at present, we report a case of fatal clostridial sepsis secondary to a septic spontaneous abortion. A woman at 6-8 weeks' gestation presented with vaginal bleeding and abdominal pain. Although afebrile, the patient was hypotensive, tachycardic, and tachypneic. Physical examination was remarkable for a 10-weeks'-gestation-size uterus, mild pelvic tenderness, a closed cervix without signs of trauma, and moderate vaginal bleeding. Laboratory studies were consistent with infection, hemolysis, and coagulopathy. Sonography demonstrated echolucencies consistent with gas formation in the endometrial cavity. Despite fluid resuscitation, transfusions, antibiotic therapy, and a dilation and curettage, persistent vaginal bleeding required an emergency hysterectomy. Hypotension ensued, and despite aggressive resuscitation attempts, the patient died. Rare cases of fatal sepsis secondary to pelvic infection with Clostridium perfringens continue to occur. Hemolysis, anuria, coagulopathy, and characteristic sonographic findings should heighten suspicion of this potentially fatal infection.


Prognostic significance of histopathologic subtype and stage in small cell lung cancer.
A study of 149 light microscopic tissue slides from 147 patients with recorded initial diagnoses of small cell lung cancer (SCLC) (114 cases) and undifferentiated carcinoma (35 cases) was undertaken to test the reproducibility and prognostic impact of a new histopathologic subclassification of SCLC proposed by the Pathology Panel of the International Association for the Study of Lung Cancer (IASLC). This study was further designed to test the impact of clinical stage, age, sex, and race on survival. The tissue slides were blindly reclassified as SCLC or non-SCLC by a panel of five pathologists with no knowledge of the initial diagnosis. The SCLCs were divided into the three subtypes outlined by the IASLC pathology panel: small (classic or pure), mixed (small cell/large cell), and combined (small cell/squamous carcinoma or small cell/adenocarcinoma). Small cell lung cancer was clinically staged as local, regional, or distant. Consensus diagnosis (defined as agreement by at least three of the five pathologists) was achieved in 144 (96.6%) of the 149 cases. Of these 144 cases, 124 were reclassified as SCLC (115 [92.8%] small, five [4.0%] mixed, and four [3.2%] combined) and 20 were classified as non-SCLC. The median lengths of survival for the small, mixed, and combined subtypes were 225, 1,110, and 203 days, respectively (P = .025). Adequate staging data were available in 123 of the 124 SCLC cases. Of the 123 SCLC cases, 27 (21.9%) were local, 22 (17.9%) were regional, and 74 (60.2%) were distant stage. The median lengths of survival for the local, regional, and distant stages were 428, 251, and 111 days, respectively. This association was highly significant (P = .0001). We conclude that stage is the major determinant of survival in SCLC. Mixed subtypes had significantly longer survival times than the small or combined subtypes (P = .025). Survival times were longer for women than for men, and the survival time difference between men and women was significant (P = .0028). We found no significant differences in survival according to age or race.


Ulcerated Nodule in Patient with Talaromycosis: Re-visit a Neglected Disease in the Era of Antiretroviral Therapy.
Talaromycosis is among common opportunistic infections in patients with AIDS living in the endemic area, although the incidence is declining in the era of antiretroviral therapy. Here, we present a case of disseminated infection in a patient who was unaware of HIV-serostatus and did not receive antiretroviral therapy.


Fibroblast growth factor causes an early increase in phosphorylation of a membrane protein in quiescent 3T3 cells.
THE regulatory systems controlling cell division have not been identified, but it has been shown that growth factors such as epidermal growth factor, fibroblast growth factor (FGF), and serum initiate rapid changes in cellular metabolism, probably involving post-transcriptional control mechanisms(1-5). As phosphorylation has been shown to be an important regulatory mechanism in several metabolic pathways, we initiated experiments to determine whether factors which stimulate DNA synthesis also stimulate endogenous phosphorylation. We find mat, within 5 min of addition of FGF or serum to (32)P-labelled Swiss 3T3 cells, there is a specific increase in the phosphorylation of a membrane protein with an apparent molecular weight of 33,000. Experiments with isolated cell fractions demonstrate that the phosphorylation of this protein is stimulated by cyclic AMP. This rapid and specific response to mitogens raises the possibility that this phosphorylation might be part of the initial, cellular signal for DNA synthesis.


Effect of competitive myoneural blockade and fentanyl on muscle fasciculation caused by suxamethonium in children.
The effects of tubocurarine 0.06 mg kg-1, alcuronium 0.03 mg kg-1, pancuronium 0.01 mg kg-1, and fentanyl 1 or 2 micrograms kg-1 on the muscle fasciculations associated with suxamethonium were studied in 171 children undergoing otolaryngological surgery. The mean fasciculation index in all pretreatment groups was significantly smaller than in the control group. The most effective pretreatment was fentanyl 2 micrograms kg-1 followed, in order, by alcuronium, fentanyl 1 microgram kg-1, tubocurarine and pancuronium. The rate of the onset of the fasciculations after the injection of suxamethonium ranged from 8 s after pancuronium to 20 s after tubocurarine. There was evidence of respiratory depression in the children receiving fentanyl 2 micrograms kg-1 if the duration of anaesthesia was less than 30 min.


Visualization of renal autoregulation in the split hydronephrotic kidney of rats.
The autoregulatory ability of the renal vascular system in the split hydronephrotic kidney was quantitated with intravital microscopy. The luminal diameters of the arcuate and interlobular arteries as well as the afferent and efferent arterioles were measured. Glomerular blood flow was determined by the dual slit technique. In the first series of experiments, the renal perfusion pressure was reduced by graded clamping of the abdominal aorta. Pressure reduction from 118 mm Hg to 95 mm Hg induced dilation of all preglomerular vessels except for the distal afferent arteriole; there was no change in the efferent arteriole and the blood flow was maintained. Further pressure reductions to 71 and 43 mm Hg caused additional dilations of the preglomerular vessels, a marginal reduction in diameter of proximal efferent arterioles and flow reductions by 15% and 41%, respectively. In the second series, systemic blood pressure was increased by continuous i.v. infusions of norepinephrine (NE). NE constricted pre- and postglomerular vessels except for the distal afferent arteriole; glomerular flow was decreased. Reduction of renal perfusion pressure during NE infusion to the preinfusion value did not diminish glomerular blood flow, but reduced the constrictor response to NE in preglomerular vessels. In a third series of experiments we examined the effect of atrial natriuretic factor (ANF) on renal autoregulation. Addition of ANF (10(-9) to 10(-7) M) to the renal bath induced a dose-dependent dilation of all preglomerular vessels and a constriction of the efferent arteriole. Pressure reduction from 120 to 95 mm Hg resulted in a further preglomerular vasodilation. These experiments demonstrate that autoregulation is mediated primarily by diameter changes in all preglomerular vessels excluding the distal segment of the afferent arteriole. Further, these data suggest that ANF induced dilation of preglomerular vessels does not impair the myogenic response of these vessels.


Therapeutic hypothermia limited to the resuscitation period does not prolong survival after severe hemorrhagic shock in rats.
Controlled hypothermia induced during hemorrhagic shock (HS) has been shown previously to improve survival in HS rat outcome models. We hypothesized that hypothermia (34 degrees C) induced immediately with reperfusion would also improve survival. Twenty-four rats were lightly anesthetized with halothane and maintained spontaneous breathing. The rats underwent: an HS phase I of 75 min, with an initial blood withdrawal of 2.5 mL/100 g over 15 min, followed by either additional blood withdrawal or re-infusion in order to maintain a mean arterial pressure (MAP) of 30 mmHg over 60 min; a resuscitation phase II of 60 min with return of shed blood and infusion of lactated Ringer's solution to maintain a MAP of 75 mmHg; and an observation phase III without anesthesia for 72 h. Five minutes before the start of phase II, 12 rats were randomized into either a normothermia (38 degrees C) group or hypothermia (34 degrees C) group. The rectal temperature in each group was carefully maintained during the 60-min period of phase II. Survival at 72 h, as well as gut damage were assessed. All 24 rats survived beyond phases I and II. At 72 h, 8 of 12 rats survived in the hypothermia group, while and 6 of 12 survived in the normothermia group (p=0.64). Intestines of the 72 h survivors were macroscopically normal. In rats that died during phase III, total gut scores did not differ statistically between the groups (1.2+/-0.6 versus 1.0+/-0.9). Brief resuscitative hypothermia of 60 min duration induced immediately with reperfusion after HS did not improve survival in this model.


HDL-like discs for assaying membrane proteins in drug discovery.
To broaden the use of the recombinant high-density lipoprotein (rHDL) approach to the characterization of lead compounds, we investigated the pharmacology of the human beta-2-adrenoceptor in nanolipid bilayers (rHDL) with a broad set of beta-adrenoceptor antagonists. To that end, we developed a homogeneous copper-chelate scintillation proximity binding assay (SPA) in order to compare receptor-ligand binding affinities before and after reconstitution into rHDLs. Our results clearly show that the beta-2-adrenoceptor reconstituted in rHDLs display the same pharmacology as that in cell membranes and that rHDLs can be used not only to measure affinities for a range of ligands but also to study binding kinetics.


Evaluation of the medication process in pediatric patients: a meta-analysis.
to meta-analyze studies that have assessed the medication errors rate in pediatric patients during prescribing, dispensing, and drug administration. searches were performed in the PubMed, Cochrane Library, and Trip databases, selecting articles published in English from 2001 to 2010. a total of 25 original studies that met inclusion criteria were selected, which referred to pediatric inpatients or pediatric patients in emergency departments aged 0-16 years, and assessed the frequency of medication errors in the stages of prescribing, dispensing, and drug administration. the combined medication error rate for prescribing errors to medication orders was 0.175 (95% Confidence Interval: [CI] 0.108-0.270), the rate of prescribing errors to total medication errors was 0.342 (95% CI: 0.146-0.611), that of dispensing errors to total medication errors was 0.065 (95% CI: 0.026-0.154), and that ofadministration errors to total medication errors was 0.316 (95% CI: 0.148-0.550). Furthermore, the combined medication error rate for administration errors to drug administrations was 0.209 (95% CI: 0.152-0.281). Medication errors constitute a reality in healthcare services. The medication process is significantly prone to errors, especially during prescription and drug administration. Implementation of medication error reduction strategies is required in order to increase the safety and quality of pediatric healthcare.


A Comparative Study between Follicular Unit Transplantation and Autologous Non-cultured Non-trypsinized Epidermal Cells Grafting (Jodhpur Technique) in Stable Vitiligo.
Several modalities are currently available for the treatment of vitiligo, but generally they do not result in complete cure of the disease. Despite the limitations and some side effects, surgical modalities appear to be the method of choice in recalcitrant stable vitiligo. Both Jodhpur technique (JT) and follicular unit transplantation (FUT) are simpler and cheaper methods, requiring minimal infrastructure. Hundred patches in 30 patients were divided into Group A and Group B, that is, hair follicle transplantation and autologous non-cultured non-trypsinized epidermal cell suspension grafting (JT), respectively. Fifty patches were included in each group. Efficacy of both the techniques, extent of pigmentation, and color match assessment were the main objectives. Excellent repigmentation (>75%), at the end of 20 weeks post surgery, was observed in 70% lesions in FUT group and 72% of lesions in JT group. Good response (extent of repigmentation of 50%-75%) was seen in 18% of lesions in FUT group as compared to 26% in JT group. JT and FUT technique were almost equal in producing excellent repigmentation. Color match was same for both the groups, that is, 49 of 50 patches showed same color as surrounding in both groups at the end of 20 weeks. Repigmentation of the depigmented hairs occurred in 11 of 46 patients with associated leukotrichia. Our study indicates that both JT and FUT are safe and effective techniques in terms of repigmentation but JT is somewhat superior to FUT in producing excellent and good repigmentation, side effects, patient satisfaction, and dermatology life quality index reduction, while the color match was almost same with both techniques.


Update on Computed Tomography Myocardial Perfusion Imaging.
Computed tomography (CT) coronary angiography is a well-validated non-invasive technique for accurate and expedient diagnosis of coronary artery disease (CAD). However, a limitation of coronary CT angiography (CCTA) is its limited capability to identify physiologically significant stenoses, which may eventuate the need for further functional testing. Stress CT myocardial perfusion imaging (CT-MPI) is an emerging technique that has the ability to identify flow-limiting stenoses. The combination of CCTA coronary and CT-MPI has transformed the modality from a tool to assess anatomy and morphology to a modality capable of simultaneous assessment of coronary stenoses and their physiologic significance. A growing number of studies have demonstrated the feasibility and diagnostic accuracy of CT-MPI in comparison to a number of reference standard modalities for CAD diagnosis, including single-photon emission CT, cardiovascular magnetic resonance imaging, and invasive coronary angiography with and without fractional flow-reserve testing. While there is still a need for consensus regarding acquisition techniques as well as analysis and interpretation of CT-MPI, with further validation, it is likely to become a powerful adjunctive tool to CCTA in the management of patients with suspected coronary disease.


Development of an HPLC method for the analysis of Apomine in a topical cream formulation.
A stability indicating, reversed-phase high performance liquid chromatographic method was developed for the quantification of Apomine, tetraisopropyl 2-(3,5-di-tert-butyl-4-hydroxyphenyl)-ethyl-1, 1-bisphosphonate, in a topical cream formulation. Analysis of Apomine in the cream formulation was performed through a dilution of the cream base with tetrahydrofuran. This allowed the current method to bypass extraction and/or centrifugation for direct injection and analysis. Separation was achieved using an Alltima C18 5 microm, 150 mm x 2.1 mm column and employed a gradient procedure, beginning with acetonitrile-water (65:35, v/v), at 0.6 mL/min for 9 min, followed by a rinse with isopropyl alcohol for 9 min. The complete gradient method has been optimized to separate Apomine from the nonpolar cream components, wash and equilibrate the column in a 30-min assay. This report demonstrates that this method is effective for quantification of Apomine in a cream formulation.


β-Resorcylidene aminoguanidine (RAG) dilates coronary arteries in an endothelium-independent manner.
β-Resorcylidene aminoguanidine (RAG), a highly reactive derivative of aminoguanidine, possesses antithrombotic activity which involves the activation of the vascular COX-2/PGI2 pathway. This endothelium-dependent effect suggests that RAG may demonstrate vasomotor activity in arterial vessels. The aim of the present study was to investigate a possible vasoactive action of RAG in coronary arteries of rat heart. Isolated rat hearts were perfused in the Langendorff model. To investigate the dose dependency of the effect of RAG on coronary flow, the hearts were perfused with RAG at increasing concentrations. Mechanisms of RAG-mediated vasodilation were subsequently tested using selective inhibitors of the endothelium-dependent and endothelium-independent mechanisms responsible for regulation of vascular tone. RAG dilated coronary arteries at concentrations above 10(-5)mol/l. Inhibition of the endothelium-dependent mechanism of vasodilation by NG-nitro-L-arginine methyl ester, indomethacin and aminobenzotriazole did not affect RAG-mediated vasodilation. Other compounds also had no impact on the vasodilating effect of RAG: the NO-dependent guanylate cyclase inhibitor - 1H-[1,2,4]oxadiazolo[4,3]quinoxalin-1-one, the cAMP-dependent protein kinase inhibitor - PKAi, and the K(+) channel blockers - glibenclamide, tetraethylammonium, charybdotoxin, and apamin. RAG is a strong vasodilator that exerts its effect via endothelium-independent mechanisms.


Mobility following cesarean delivery: an observational study utilizing pedometers.
Introduction: Thromboembolic events are a leading cause of maternal death, and peak in the postpartum period. We aimed to assess immediate patient mobility following cesarean delivery (CD) with digital step counters (pedometers), and to characterize factors associated with reduced mobility.Materials and methods: This was a prospective observational study at the maternity unit of the Edith Wolfson Medical Center between June 2017 and February 2018. Patients who underwent a cesarean - primary and repeat, and emergent and nonemergent - were asked to wear pedometers for 48 h following cesarean. Comparison of maternal characteristics, surgical, and postpartum course was performed between three groups: high mobility patients (n = 33), intermediate mobility patients (n = 34), and low mobility patients (n = 34), according to the upper third of steps recorded, intermediate third, and the lower third, respectively.Results: The average number of steps taken during the first 48 h following delivery was 6974 ± 2582, 2724 ± 732, and 1056 ± 454 in the high, intermediate, and low mobility groups, respectively, p < .001. Patients' demographics, parity, intrapartum, and postpartum course were not found to be associated with patient mobility. However, smokers were found to walk an additional 1549 steps following CD as compared to nonsmokers.Conclusion: This study failed to identify risk factors for reduced mobility in the immediate postpartum period, but an increased mobility was noted in smokers, most probably related to the need to ambulate outside the maternity ward. The decision to treat patients following a cesarean with thromboprophlaxis will continue to be based on previously identified risk factors.


Antimicrobial agents in adult patients with renal insufficiency: initial dosage and general recommendations.
The dosage or the time interval of administration (or both) of many antimicrobial agents must be adjusted in anephric patients or those with compromised renal function. Antimicrobial agents that must have adjustment of dosages include most, but not all, of the penicillins and cephalosporins, the aminoglycosides, vancomycin, and trimethoprim-sulfamethoxazole. The maximal doses of these agents generally should be decreased in proportion with the extent of reduction in renal function. The dosage of chloramphenicol, clindamycin, rifampin, nafcillin, and ceftriaxone probably need not be adjusted if hepatic function is essentially normal. The suggested doses are relatively crude guidelines to initial antimicrobial therapy. Serum antimicrobial assays are frequently indicated for accurate adjustment of the dosage, especially with the amino-glycosides. The efficacy of therapy and the possible occurrence of toxicity should be monitored in all patients but particularly in those with renal insufficiency. Recommendations for patients undergoing peritoneal dialysis are not included in this article.


Effect of mesenchymal stem cells on inhibiting airway remodeling and airway inflammation in chronic asthma.
Previous studies proved that bone marrow-derived mesenchymal stem cells (BMSCs) could improve a variety of immune-mediated disease by its immunomodulatory properties. In this study, we investigated the effect on airway remodeling and airway inflammation by administrating BMSCs in chronic asthmatic mice. Forty-eight female BALB/c mice were randomly distributed into PBS group, BMSCs treatment group, BMSCs control group, and asthmatic group. The levels of cytokine and immunoglobulin in serum and bronchoalveolar lavage fluid were detected by enzyme-linked immunosorbent assay. The number of CD4(+) CD25(+) regulatory T cells and morphometric analysis was determined by flow cytometry, hematoxylin-eosin, immunofluorescence staining, periodic-acid Schiff, and masson staining, respectively. We found that airway remodeling and airway inflammation were evident in asthmatic mice. Moreover, low level of IL-12 and high levels of IL-13, IL-4, OVA-specific IgG1, IgE, and IgG2a and the fewer number of CD4(+) CD25(+) regulatory T cells were present in asthmatic group. However, transplantation of BMSCs significantly decreased airway inflammation and airway remodeling and level of IL-4, OVA-specific IgE, and OVA-specific IgG1, but elevated level of IL-12 and the number of CD4 + CD25 + regulatory T cells in asthma (P < 0.05). However, BMSCs did not contribute to lung regeneration and had no significant effect on levels of IL-10, IFN-Y, and IL-13. In our study, BMSCs engraftment prohibited airway inflammation and airway remodeling in chronic asthmatic group. The beneficial effect of BMSCs might involved the modulation imbalance cytokine toward a new balance Th1-Th2 profiles and up-regulation of protective CD4 + CD25 + regulatory T cells in asthma, but not contribution to lung regeneration.


Thymic Germinal Centers and Corticosteroids in Myasthenia Gravis: an Immunopathological Study in 1035 Cases and a Critical Review.
The most common form of Myasthenia gravis (MG) is due to anti-acetylcholine receptor (AChR) antibodies and is frequently associated with thymic pathology. In this review, we discuss the immunopathological characteristics and molecular mechanisms of thymic follicular hyperplasia, the effects of corticosteroids on this thymic pathology, and the role of thymic epithelial cells (TEC), a key player in the inflammatory thymic mechanisms. This review is based not only on the literature data but also on thymic transcriptome results and analyses of pathological and immunological correlations in a vast cohort of 1035 MG patients without thymoma. We show that among patients presenting a thymic hyperplasia with germinal centers (GC), 80 % are females, indicating that thymic follicular hyperplasia is mainly a disease of women. The presence of anti-AChR antibodies is correlated with the degree of follicular hyperplasia, suggesting that the thymus is a source of anti-AChR antibodies. The degree of hyperplasia is not dependent upon the time from the onset, implying that either the antigen is chronically expressed and/or that the mechanisms of the resolution of the GC are not efficiently controlled. Glucocorticoids, a conventional therapy in MG, induce a significant reduction in the GC number, together with changes in the expression of chemokines and angiogenesis. These changes are likely related to the acetylation molecular process, overrepresented in corticosteroid-treated patients, and essential for gene regulation. Altogether, based on the pathological and molecular thymic abnormalities found in MG patients, this review provides some explanations for the benefit of thymectomy in early-onset MG patients.


Exposure of the endangered Milky stork population to cadmium and lead via food and water intake in Kuala Gula Bird Sanctuary, Perak, Malaysia.
The Milky stork is listed as an endangered species endemic to the Southeast Asia region. In Malaysia, the population is currently being reintroduced back into the wild. However, the increase of anthropogenic activity throughout the coastal area might expose the population to hazardous chemicals such as heavy metals. This study highlights the contamination of cadmium (Cd) and lead (Pb) in the Milky stork's diet. Additionally, this is the first time an integrated exposure model being used to assess heavy metal exposure risk to the population. Lead level (5.5-7.98 mg kg-1) in particular was relatively high compared to Cd (0.08-0.33 mg kg-1). This was probably related to the different niches occupied by the species in the aquatic environment. The results further show that the predicted exposure doses (through intake of both food and water) for all metals are much lower than the Tolerable Daily Intake (TDI) values. The total exposure dose for Cd was 0.11 mg kg-1 d-1 with TDI value of 0.54 mg kg-1 d-1 while Pb total exposure dose was 0.31 mg kg-1 d-1 with TDI value of 0.64 mg kg-1 d-1. Several possible factors that could lead to the observed pattern were discussed. In conclusion, there is an urgent need to improve the current habitat quality to protect the endangered species. The authors also emphasized on the protection of remaining Milky stork's habitats i.e. mudflats and mangroves and the creation of buffer zone to mitigate the negative impacts that may arise from pollution activity.


Cardiovascular event rates and trajectories of LDL-cholesterol levels and lipid-lowering therapy in patients with atherosclerotic cardiovascular disease: A population-based cohort study.
An understanding of cardiovascular event rates and low-density lipoprotein cholesterol (LDL-C) levels and trajectories in patients with atherosclerotic cardiovascular disease is needed to evaluate treatment goals and adherence to guidelines. We conducted a population-based cohort study in the North and Central Denmark Regions. Patients with prevalent atherosclerotic cardiovascular disease (myocardial infarction, non-hemorrhagic stroke, or peripheral artery disease) during 2006-2009 were identified. All patients received lipid-lowering therapy (statins or ezetimibe) and had LDL-C levels ≥1.8 mmol/L at baseline (January 1, 2010). We followed patients for 6 years until a primary composite outcome of cardiovascular death, myocardial infarction, non-hemorrhagic stroke, hospitalization for unstable angina, or coronary revascularization. Additionally, we characterized changes in LDL-C levels and use of statins during follow-up. The study included 10,772 patients (median age 69.2 years, 60.4% male). The overall event rate for the primary outcome was 62.7 (95% confidence interval: 59.2-66.2) per 1000 person-years. This event rate was higher among men than among women and increased with age and baseline LDL-C levels. Approximately 25% of patients with LDL-C measurements during follow-up achieved LDL-C levels below 1.8 mmol/L. Of the approximately two-thirds of patients using statins at the end of follow-up, nearly all patients (97%) received high-intensity therapy. In this population of patients with atherosclerotic cardiovascular disease, we found high cardiovascular event rates, which increased with baseline LDL-C levels. Although most patients were on high-intensity statin therapy at end of follow-up, only one-quarter reached the guideline-recommended target LDL-C level ≤ 1.8 mmol/L.


Identification of the novel KIR3DL1*079 allele from a southern Chinese Han individual.
The novel KIR3DL1*079 allele differs from KIR3DL1*0150201 by a single mutation at CDS nt1119 G>T.


Evidence for an enterohepatic circulation of ochratoxin A in mice.
The distribution and elimination of [3H]ochratoxin A (OTA) from stomach content and tissue, intestine content and tissue, liver, bile, serum and urine of Swiss male mice which had received a single low dose of OTA by intubation was followed as a function of time. The profiles of radioactivity do not show a smooth decline after the absorption period, but an oscillating pattern with rapid declines followed by increases which favour the assumption of an enterohepatic circulation. Between 28% and 68% of conjugated OTA together with OTA cleavage products were found in bile giving evidence for biliary excretion of OTA and its metabolites in mice. When given i.m. to mice [3H]OTA is already found after 30 min in bile and intestine contents and its elimination patterns show several peaks confirming the biliary excretion and the enterohepatic circulation. Cholestyramine, which is known to prevent the enterohepatic circulation of drugs and toxins, changes the profile of elimination of OTA which no longer presents the cyclic pattern. This result is also in favour of an enterohepatic circulation of OTA. When phenylalanine is given together with OTA by oral gavage the toxicokinetics of the mycotoxin change completely in the different body fluids, in stomach and intestine content and tissues. Phenylalanine seems to facilitate the gastric absorption of OTA and the gastro-intestinal transit. It increases also its early excretion into urine and bile. However, its elimination pattern no longer shows the oscillating pattern. Thus phenylalanine seems to inhibit the intestinal reabsorption of OTA conjugates.


Soft elastomeric nanopillar stamps for enhancing absorption in organic thin-film solar cells.
An elastomeric poly(dimethylsiloxane) (PDMS) block engraved with periodically arrayed nanopillars serves as a transferable light-trapping stamp for encapsulated organic thin-film solar cells. Diffracted light rays from the stamp interfere with one another and self-focus onto the active layer of the solar cell, generating enhanced absorption, as indicated in the current density-voltage measurements.


Preclinical toxicology of the anticonvulsant calcium valproate.
The oral toxicity of the anticonvulsant calcium valproate with selected comparisons to valproic acid and sodium valproate was evaluated in mice, rats and Beagle dogs. Median lethal doses of the three forms of valproate in rodents ranged from 1100 to 3900 mg/kg. Clinical signs in acute studies and reductions in body weight or body weight gain and food consumption at high doses in rats and dogs during 2-, 13- and 52-week studies were considered to be central nervous system related. In the 13-week study in rats (calcium valproate at 200, 400, 800, 1200 and 1600 mg/kg and sodium valproate at 1200 mg/kg), reduced plasma globulin levels and low white blood cell counts due to suppressed neutrophil maturation were noted at doses of 800 mg/kg and higher. Platelet counts were reduced at 1200 and 1600 mg/kg. Testicular atrophy occurred at 1200 and 1600 mg/kg. In dogs given calcium valproate at 100, 200 and 400 mg/kg for 13 weeks, testicular atrophy was seen at 400 mg/kg and mild hepatocellular changes at all doses. In rats given calcium valproate at 125, 250 and 500 mg/kg for 1 year, reduced plasma protein and globulin levels and a dose-dependent increased incidence and severity of atrophic pancreatitis were noted at 250 and 500 mg/kg. Calcium valproate, given for 1 year to dogs at doses of 50, 100 and 200 mg/kg, was well tolerated. These studies indicated that calcium valproate has a toxicity profile similar to other forms of valproate.


GENPRO: automatic generation of Prolog clause files for knowledge-based systems in the biomedical sciences.
With the increasing interest in using knowledge-based approaches for protein structure prediction and modelling, there is a requirement for general techniques to convert molecular biological data into structures that can be interpreted by artificial intelligence programming languages (e.g. Prolog). We describe here an interactive program that generates files in Prolog clausal form from the most commonly distributed protein structural data collections. The program is flexible and enables a variety of clause structures to be defined by the user through a general schema definition system. Our method can be extended to include other types of molecular biological database or those containing non-structural information, thus providing a uniform framework for handling the increasing volume of data available to knowledge-based systems in biomedicine.


Carrier state for the nebulin exon 55 deletion and abnormal prenatal ultrasound findings as potential signs of nemaline myopathy.
To increase awareness to the possibility of nemaline myopathy (NM) when abnormal prenatal ultrasound findings appear together with a carrier state for the common exon 55 deletion in the nebulin gene (NEB) of an Ashkenazi Jewish parent. We describe four unrelated pregnancies with abnormal prenatal ultrasound findings resulting in the birth of newborns with NM, where one or both parents were of Ashkenazi Jewish origin. Data was collected retrospectively from the patients' medical files. Molecular analysis of NEB was performed on the DNA from the patients and parents. Prenatal ultrasound findings included polyhydramnios, decreased fetal movements, club feet, and arthrogryposis. A biopsy from two of the newborns was consistent with NM. In all of the newborns, the common NEB exon 55 deletion was detected in the heterozygote state and in three of them, a second novel mutation was found. Ultrasonographic findings suggestive of a myopathy and a carrier state for the NEB exon 55 deletion in one of the parents should trigger a thorough investigation for NM. The extreme size of NEB imposes great difficulties when searching for a second mutation, especially under the time constraints of an ongoing pregnancy.


Effects of fiscal decentralisation on the environment: new evidence from China.
The aim of this paper is to explore the environmental effects of fiscal decentralisation from theoretical and empirical perspectives. We first analyse the dynamic relationship between fiscal decentralisation and the environment using an endogenous growth model. Our findings demonstrate that fiscal decentralisation and environmental pollution display an inverted U-shaped relationship. We then use provincial panel data from 1998 to 2015 in the empirical investigation of CO2 emissions in China. Our findings show that empirical results verify the correctness of the theoretical results. The results obtained are robust using different methods. The findings of this work may help China's central government and local governments in addressing the problem of CO2 emissions by using a reasonable degree of fiscal decentralisation.


Evaluation of a therapeutic concentration of dithranol in the mouse-tail test.
A study of dithranol ointment in the mouse-tail test showed that 0.2% dithranol ointment induced a granular layer and orthokeratosis in mouse-tail epidermis. This provides further evidence of the value of the mouse-tail test in evaluating anti-psoriatic activity of topical preparations.


Treatment for periprosthetic infection with two-stage revision arthroplasty with a gentamicin loaded spacer. The clinical outcomes.
With the increasing number of total joint replacement procedures, the number of complications from that surgery has also been on the rise. Although quite rare (<1%), a PPI may ruin even the best and technically excellent joint replacement procedure, causing extensive damage and loss of bone and periprosthetic tissues, which makes subsequent restoration surgery extremely difficult. At present, a two-stage revision arthroplasty seems to be the best solution for PPI patients [4,9,15]. In the first stage, implant removal and radical débridement of infected tissues is performed and an antibiotic-loaded spacer is inserted. After a few months, the second stage is performed where the spacer is removed and a revision endoprosthesis is implanted. The aim of the study was to evaluate the effectiveness of treatment for periprosthetic infections with a two-stage revision arthroplasty. Forty-one patients diagnosed with PPI were treated at the Department of Orthopedic and Trauma Surgery, Silesian Medical University in Katowice, between January 2007 and March 2010. PPI was a complication of knee arthroplasty (12 patients, 29%) and hip replacement (29 patients, 71%). During the first stage of the treatment, intraoperative cultures were negative in 17 patients (41%) and positive in 24 (59%). Cultures obtained in patients with reinfection after revision endoprosthesoplasty (second stage of the treatment) grew no pathogen in 1 patient, MSSA (1), E. faecalis (1), and A. baumanii with MSSA and MRSE (1). After the first stage of the treatment (spacer implantation), infection was not cured in one patient (2.5%). In 4 patients (10%), there was reinfection after the implantation of a revision endoprosthesis. Our analysis provides evidence to suggest that two-stage revision endoprosthesoplasty is an effective method of treatment of periprosthetic infections.


Impact of China's establishment of ecological civilization pilot zones on carbon dioxide emissions.
Since China's speedy economic development, the problems of energy consumption and environmental pollution have become increasingly prominent. A question worth in-depth study is whether ecological civilization (EC) construction, one of the main policies to solve China's severe environmental and ecological problems, affects carbon dioxide emissions (CDE). In this study, we use a novel method proposed by Hsiao et al. (2012) to estimate the average treatment effect by using panel data to study the impact of establishing the EC pilot zones of China on CDE. The results show that, although EC construction is effective in reducing CDE, the impact varies from region to region. The study findings can provide a scientific basis to promote the experience of EC construction better and improve its CDE effect.


Enzymatic conversion of D-galactose to D-tagatose: cloning, overexpression and characterization of L-arabinose isomerase from Pediococcus pentosaceus PC-5.
The gene encoding L-arabinose isomerase from food-grade strain Pediococcus pentosaceus PC-5 was cloned and overexpressed in Escherichia coli. The recombinant protein was purified and characterized. It was optimally active at 50 °C and pH 6.0. Furthermore, this enzyme exhibited a weak requirement for metallic ions for its maximal activity evaluated at 0.6 mM Mn(2+) or 0.8 mM Co(2+). Interestingly, this enzyme was distinguished from other L-AIs, it could not use L-arabinose as its substrate. In addition, a three-dimensional structure of L-AI was built by homology modeling and L-arabinose and D-galactose were docked into the active site pocket of PPAI model to explain the interaction between L-AI and its substrate. The purified P. pentosaceus PC-5 L-AI converted D-galactose into D-tagatose with a high conversion rate of 52% after 24 h at 50 °C, suggesting its excellent potential in D-tagatose production.


Substance P inhibits the M-current in bullfrog sympathetic neurones.
Substance P (SP, 2.5-10 microM) was applied by rapid bath perfusion to bullfrog lumbar sympathetic neurones in vitro, voltage-clamped through a single micro-electrode. In unclamped cells, SP produced a depolarization accompanied by an increase in apparent input resistance. Under voltage-clamp a voltage-dependent inward current was induced by SP, during which the time-dependent relaxations induced by square voltage commands were inhibited. It is concluded that SP inhibits the M-current (IM), a species of voltage-dependent K+-current, and that IM-inhibition was the primary cause of the inward current and membrane depolarization in the cells tested.


Pacemaker-mediated tachycardias: an unresolved problem.
The advent of dual chamber pacing systems that restore atrioventricular synchrony and allow rate variability in response to physiologic stress has provided a major advance in pacing therapy. Undesirable pacemaker-mediated tachycardias may arise when the atrial sensing amplifier of a VDD or DDD device detects a retrogradely conducted P-wave, ectopic atrial tachycardia, myopectoral contractions, or environmental electromagnetic interference. The rate of the resultant tachycardia is determined by the programmed upper tracking rate of the pacemaker. Although seldom life-threatening, troublesome myocardial ischemia may ensue in patients with coronary artery disease. In most instances, the incidence and rate of pacemaker-mediated tachycardias may be minimized by judicious programming.


Tumor necrosis factor-α stimulation endothelial-to-mesenchymal transition during cardiac fibrosis via endothelin-1 signaling.
Cardiac fibrosis is an important pathological change after myocardial infarction (MI). High concentration of tumor necrosis factor-α (TNF-α) contributes to cardiac fibrosis, and TNF-α has been demonstrated to be involved in transforming growth factor-β1-induced endothelial-to-mesenchymal transition (EndMT). However, the role and molecular mechanisms of TNF-α during cardiac fibrosis remain largely unexplored. In this study, we demonstrated that TNF-α and endothelin-1 (ET-1) were upregulated in cardiac fibrosis after MI, and genes associated with EndMT were also upregulated. An in vitro model of EndMT demonstrated that TNF-α promoted EndMT by upregulation of vimentin and α-smooth muscle actin, and which strongly increased ET-1 expression. ET-1 promoted TNF-α-induced expression of gene program through phosphorylation levels of SMAD family member 2, while subsequent inhibition of ET-1 almost abolished the effect of TNF-α during the process of EndMT. In summary, these findings demonstrated that ET-1 is involved in the EndMT induced by TNF-α during cardiac fibrosis.


Applied machine learning in cancer research: A systematic review for patient diagnosis, classification and prognosis.
Artificial Intelligence (AI) has recently altered the landscape of cancer research and medical oncology using traditional Machine Learning (ML) algorithms and cutting-edge Deep Learning (DL) architectures. In this review article we focus on the ML aspect of AI applications in cancer research and present the most indicative studies with respect to the ML algorithms and data used. The PubMed and dblp databases were considered to obtain the most relevant research works of the last five years. Based on a comparison of the proposed studies and their research clinical outcomes concerning the medical ML application in cancer research, three main clinical scenarios were identified. We give an overview of the well-known DL and Reinforcement Learning (RL) methodologies, as well as their application in clinical practice, and we briefly discuss Systems Biology in cancer research. We also provide a thorough examination of the clinical scenarios with respect to disease diagnosis, patient classification and cancer prognosis and survival. The most relevant studies identified in the preceding year are presented along with their primary findings. Furthermore, we examine the effective implementation and the main points that need to be addressed in the direction of robustness, explainability and transparency of predictive models. Finally, we summarize the most recent advances in the field of AI/ML applications in cancer research and medical oncology, as well as some of the challenges and open issues that need to be addressed before data-driven models can be implemented in healthcare systems to assist physicians in their daily practice.


Regulation of miRNAs by agents targeting the tumor stem cell markers DCLK1, MSI1, LGR5, and BMI1.
Gastrointestinal cancers such as colorectal, pancreatic, liver, gastric, and esophageal, are the most common forms of malignant cancers. MicroRNAs (miRNA) play important role in regulating gastrointestinal cancer progress either as potent oncogenes or tumor suppressors. In this report, we will discuss the importance of several tumor suppressors involved in colon or pancreatic cancer. Some recent studies on tumor stem cells and regulation of these miRNAs via agents targeting the tumor stem cell markers doublecortin-like kinase 1 (DCLK1), Musashi-1 (MSI1), polycomb protein BMI1, and WNT genes (LGR5 and ASCL2) will also be discussed. Agents such as siRNA/shRNA, small molecule kinase inhibitors, and general herbal drugs (curcumin) targeting these tumor stem cell markers and tumor suppressor miRNAs could be the perfect therapeutic agents for the treatment of these cancers.


Condom breakage during commercial sex in Chiang Mai, Thailand.
Used condoms in 30 female brothels in Chiang Mai, Thailand, during the period from August 1992 to October 1992 were examined for breakage. Data were also collected by interviewing 326 prostitutes who accounted for 65 percent of the total prostitutes providing condoms. The prostitutes had a mean age of 20.6 +/- 3.2 years. Sixty-one percent had no formal education. The median duration of prostitution was 13 months. The average number of clients per day in the past 24 hours and in the past 3 months was 4.4 +/- 2.5 and 5.5 +/- 2.2, respectively. Eighty-eight percent charged between $2 and less than $8 for their sexual service. All refused to practice oral or anal sex during the past 24 hours. Of 5,559 condoms, 298 were used two at a time and 15 were used three at a time. The breakage rate per act of intercourse was 5.9 percent (95% CI = 5.3, 6.5). The breakage per total condoms examined was 5.7 percent (95% CI = 5.1, 6.3). Breakage relating to manufacturing defect, i.e., pinholes, and that relating to use was 0.8 percent (95% CI = 0.6, 1.0) and 5.0 percent (95% CI = 4.4, 5.6), respectively. The probability of breakage when using two condoms at the same time was 3.4 percent (95% CI = 0.5, 6.3). Most of the breakage occurred at the distal part of the condom. There was no difference between the breakage rates of condoms provided by the brothels and those brought by the client; nor was there any difference between manufacturing defect or use. The breakage rate per client as estimated by prostitutes in the past 24 hours corroborated with that assessed by examination.


Cyclic nucleotides in the rat neostriatum: push-pull perfusion studies.
A push-pull perfusion technique was employed for in vivo study of adenosine 3',5'-monophosphate (cAMP) and guanosine 3',5'-monophosphate (cGMP) in the rat caudate nucleus. Addition of dopamine to the perfusion fluid elicited dose-dependent increases of both cAMP and cGMP perfusate concentrations. In separate experiments, it was found that pretreatment of animals with the dopamine antagonist, pimozide, significantly depressed both nucleotide responses to dopamine perfusion over the dose range studied. Mechanistic interpretations of the observations are considered. The push-pull perfusion technique appears to provide an extremely useful means of examining extracellular cyclic nucleotide levels in a discrete brain region, in vivo, under dynamic conditions.


Pregnant and breastfeeding women's attitudes and fears regarding the COVID-19 vaccination.
The COVID-19 vaccination is probably the most important source to fight the COVID-19 pandemic. However, recommendations and possibilities for vaccination for pregnant and breastfeeding women are inconsistent and dynamically changing. An anonymous, online, cross-sectional survey was conducted among pregnant and breastfeeding women in Germany between 30th March and 19th April 2021 addressing COVID-19 vaccination attitudes including the underlying reasons for their decision. Additionally, anxiety regarding a SARS-CoV-2 infection and a symptomatic course of the infection were evaluated. In total, 2339 women (n = 1043 pregnant and n = 1296 breastfeeding) completed the survey. During pregnancy the majority (57.4%) are not in favour of receiving the vaccine, 28.8% are unsure and only 13.8% would get vaccinated at the time of the survey. In contrast, 47.2% would be in favour to receive the vaccine, if more scientific evidence on the safety of the vaccination during pregnancy would be available. Breastfeeding women show higher vaccination willingness (39.5% are in favour, 28.1% are unsure and 32.5% not in favour). The willingness to be vaccinated is significantly related to the women's anxiety levels of getting infected and to develop disease symptoms. Main reasons for vaccination hesitancy are the women's perception of limited vaccination-specific information, limited scientific evidence on vaccination safety and the fear to harm the fetus or infant. The results provide important implications for obstetrical care during the pandemic as well as for official recommendations und information strategies regarding the COVID-19 vaccination.


Human immunodeficiency virus (HIV) Type 1 reverse transcriptase resistance mutations in hepatitis B virus (HBV)-HIV-coinfected patients treated for HBV chronic infection once daily with 10 milligrams of adefovir dipivoxil combined with lamivudine.
Adefovir dipivoxil (ADV) at a suboptimal concentration for human immunodeficiency virus type 1 (HIV-1) (10 mg once daily) can be used to treat hepatitis B virus (HBV) infection in HIV-1-HBV-coinfected patients and does not, even in the case of uncontrolled HIV-1 replication, select for either ADV mutations at codons 65 and 70 or any other particular HIV-1 reverse transcriptase resistance profile.


Fatal pulmonary hypertension following renal transplantation.
We present a case of fatal pulmonary hypertension occurring in a child several years following renal transplantation for membranoproliferative glomerulonephritis. Premortem investigations failed to reveal a cause for the pulmonary hypertension. Histological features in the lung at autopsy were consistent with a diagnosis of PVOD. The possible common pathogenesis of these seemingly unrelated disorders is discussed.


Comparison of laparoscopic proximal gastrectomy with double-tract reconstruction and laparoscopic total gastrectomy in terms of nutritional status or quality of life in early gastric cancer patients.
This study aimed to evaluate the surgical outcomes of laparoscopic proximal gastrectomy (LPG) reconstructed by the double-tract method in comparison to those of laparoscopic total gastrectomy (LTG). A retrospective review of the prospectively established database identified early gastric cancer patients who underwent LPG (n = 34) or LTG (n = 46) between January 2011 and December 2015. Baseline characteristics and surgical outcomes including postoperative complications, changes in body composition, nutritional status, and quality of life (QOL) after surgery were compared between the LPG and LTG patients. Operating time was significantly longer in the LTG group (240.7 ± 43.9 vs. 211.7 ± 32.8 min, p = 0.007). The incidence of grade II or more complications and the hospital stay were comparable between the groups. There was no significant difference between the groups in terms of body composition using a bioelectrical impedance method in 1 year postoperatively. Nutritional status assessed by serum hemoglobin, iron, vitamin B12, albumin, total protein, and total cholesterol levels and postoperative changes in quality of life up to 2 years after surgery were also similar between the groups. Vitamin B12 supplementation was required in 75.4% of the patients in the LTG group and 46.5% in the LPG group within 2 years after surgery (p = 0.005). LPG with double-tract reconstruction appears superior in preventing vitamin B12 deficiency compared to LTG, particularly after 1 year after the surgery, although it offered little benefit in terms of postoperative body composition changes and QOL.


Effective size in simple metapopulation models.
A coalescent argument is used to derive the effective size in simple models with recurrent local extinctions. Several alternative methods of derivation of this result are given and compared to earlier analyses of this problem. The different methods described in this paper all give the same result, which differs from earlier ones. For two published sets of estimates of demographic parameters, metapopulation structure appears to result in a moderate reduction of effective size relative to total adult population size.


Breath acetone as a marker of energy balance: an exploratory study in healthy humans.
An exploratory study was performed on eight healthy volunteers to assess how short-term changes in energy balance and dietary carbohydrate content impact breath acetone concentrations. Participants were studied on three occasions: on each occasion, they remained fasted and in resting conditions during the first 2 h to assess basal breath acetone and blood beta-hydroxybutyrate (BOHB). During the next 6 h, they remained fasted on one occasion (F), or were fed hourly high carbohydrate (HC) or low-carbohydrate (LC) meals to induce a positive energy balance on the other two occasions. They remained in resting conditions during 4 h, then performed a 2-hour low intensity exercise (25 W) inducing a negative energy balance. In resting conditions, breath acetone and blood BOHB concentrations increased progressively compared to basal values in F, but decreased and remained low throughout the test in HC. With LC, breath acetone increased progressively, while blood BOHB decreased. This exploratory study indicates that breath acetone reliably detects a stimulation of ketogenesis during a short-term fast. It also suggests that LC and HC differentially impact BOHB and acetone production and utilization, and reveals possible limitations to the use of breath acetone as a marker of energy balance.


Emerging diagnostic tools for detection of COVID-19 and perspective.
The COVID-19 caused by a novel coronavirus, named Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) has taken a great toll of life affecting lakhs of people around the globe. It was detected initially in Wuhan, China and has spread rapidly to more than 208 countries to date. A range of molecular and immunoassay-based techniques ranging from central laboratory testing to point-of-care tests is urgently needed for the diagnosis and management of COVID-19 patients. Intensive research is going on for the rapid and highly sensitive detection of COVID 19 using varied approach. Hence, this review will focus on the structure of SARS-CoV-2 and recent progress of different detection tool for the detection of COVID-19. This review will also stimulate academics and researcher to update their current technology. Additionally, we also state about the future revolving around the detection of the novel coronavirus. Lately, the way ahead for better management are also put forward.


Prognostic factors in neonatal intestinal obstruction: a prospective study of Nigerian newborns with bowel obstruction.
The management of neonatal intestinal obstruction in developing countries remains challenging, but the results are relatively less rewarding compared with results of treatment of this condition in industrialized countries. This study is an attempt to evaluate, using acceptable scientific methods, some of the factors that are believed to influence survival in neonatal intestinal obstruction, including those that are not peculiar to developing countries alone. Sixty-five babies treated for intestinal obstruction at the Lagos University Teaching Hospital, Lagos, Nigeria, formed the subjects for the study. The levels of obstruction, which were congenital in all cases, spanned the entire intestinal tract from the duodenum to the anus. Forty-one babies survived and 24 died, a survival rate of 63%. Employing Student's t test, there were no significant differences in the gestational age and birth weight between survivors and nonsurvivors, whereas significant differences do exist with respect to the age at operation and admission serum bicarbonate levels, P less than .05 and P less than .001, respectively. Analysis of the levels of obstruction and nature of operative procedure using the chi-square test shows no significant differences between the two groups. However, there is significant difference in the percentage of major associated congenital problems, P less than .01, which was higher in nonsurvivors.


Major substrate for growth factor-activated protein-tyrosine kinases is a low-abundance protein.
A scarce, soluble, conserved protein was identified as the nonphosphorylated precursor of two related 42-kilodalton phosphoproteins that contain phosphotyrosine in mitogen-stimulated but not control fibroblasts.


Absorption-Enhancing Mechanisms of Capryol 90, a Novel Absorption Enhancer, for Improving the Intestinal Absorption of Poorly Absorbed Drugs: Contributions to Trans- or Para-Cellular Pathways.
We have previously reported that Capryol 90 improves the intestinal absorption of insulin, a peptide drug, without causing serious damage to the intestinal epithelium. However, the effects of Capryol 90 and its related formulations on the intestinal absorption of other drugs, and their absorption-enhancing mechanisms are still unclear. The aim of this study is to evaluate the effects of Capryol 90 and its related formulations on the intestinal absorption of drugs and elucidate their absorption-enhancing mechanisms. The intestinal absorption of 5(6)-carboxyfluorescein, fluorescein isothiocyanate-dextrans, and alendronate was evaluated using an in situ closed loop method. Brush border membrane vesicles (BBMVs) were labeled with fluorescent probes, and the fluidity of membrane was evaluated by a fluorescence depolarization method. The expression levels of tight junction (TJ) proteins were measured using a Western blot method and immunofluorescence staining. Among the tested excipients, Capryol 90 significantly improved the small and large intestinal absorption of drugs. In mechanistic studies, Capryol 90 increased the membrane fluidity of lipid bilayers in BBMVs. Additionally, Capryol 90 decreased the expression levels of TJ-associated proteins, namely claudin-4, occludin, and ZO-1. Capryol 90 is an effective absorption enhancer for improving the intestinal absorption of poorly absorbed drugs via both transcellular and paracellular pathways.


Three-Year Outcomes After Dorsal Root Ganglion Stimulation in the Treatment of Neuropathic Pain After Peripheral Nerve Injury of Upper and Lower Extremities.
Traumatic peripheral nerve injuries (PNI) often result in severe neuropathic pain which typically becomes chronic, is recalcitrant to common analgesics, and is associated with sleep disturbances, anxiety, and depression. Pharmacological treatments proven to be effective against neuropathic pain are not well tolerated due to side effects. Neuromodulative interventions such as peripheral nerve or spinal cord stimulation have generated mixed results and may be limited by reduced somatotopic specificity. Dorsal root ganglion (DRG) stimulation may be more effective in this etiology. Twenty-seven patients were trialed with a DRG neurostimulation system for PNI; trial success (defined as ≥50% pain relief) was 85%, and 23 patients received a permanent stimulator. However, 36-month outcome data was only available for 21 patients. Pain, quality of life, mental and physical function, and opioid usage were assessed at baseline and at 3-, 6-, 12-, 18-, 24-, and 36 months post-permanent implant. Implant-related complications were also documented. Compared to baseline, we observed a significant pain relief (p < 0.001) at 3 (58%), 12 (66%), 18 (69%), 24 (71%), and 36 months (73%) in 21 patients (52.5 ± 14.2 years; 12 female), respectively. Mental and physical function showed immediate and sustained improvements. Participants reported improvements in quality of life. Opioid dosage reduced significantly (p < 0.001) at 3 (30%), 12 (93%), 18 (98%), 24 (99%), and 36 months (99%), and 20 of 21 patients were completely opioid-free after 36 months. There were five lead migrations and two electrode fractures (corrected by surgical intervention) and one wound infection (conservatively managed). DRG neuromodulation appears to be a safe, effective, and durable option for treating neuropathic pain caused by PNI. The treatment allows cessation of often ineffective pharmacotherapy (including opioid misuse) and significantly improves quality of life.