Eosinophilic esophagitis in Saudi children: symptoms, histology and endoscopy results.
Eosinophilic esophagitis (EE) is a clinicopathologic entity characterized by esophageal symptoms in association with a dense eosinophilic infiltrate currently defined as >15 eosinophils per high power field in the appropriate clinical context. This is the first pediatric study in Saudi Arabia to give the experience with EE and examine its symptom, histology and endoscopy results. Retrospective chart review of all patients diagnosed with EE at National Guard Hospital, Jeddah Between 2007 and 2009. The authors identified EE on histologic criteria (≥15 eosinophils per high-power field) together with their clinical context. The authors reviewed medical records for details of clinical presentation, laboratory data, radiologic, endoscopic, and histologic findings, and the results of treatment. We identified 15 patients in our database in the last three years. 100% of the patients were males. The median age at presentation was 10 years (range, 3-17 years). The commonly reported symptoms were failure to thrive (86%), epigastric abdominal pain (53%), poor eating (40%), dysphagia with solid food (26%), food impaction (13%), and vomiting (20%). Asthma was reported in 46% and allergic rhinitis in 40%. Peripheral eosinophilia (>0.7 Χ 10/l) was found in 66%. High serum IgE Level (>60 IU/ml) was found in 60%. Upper endoscopic analysis revealed esophageal trachealization in 46%, esophageal erythema in 46%, white specks on the esophageal mucosa in 33%, esophageal narrowing in 13%, and normal endoscopy in 13%. The mean eosinophils per high-power field was 30.4 (range, 20-71). Histologic characteristics included degranulated eosinophils (86%), basal cell hyperplasia (93%) and eosinophils clusters (micro-abscess) in 73%. The treatment of EE revealed that they used swallowed corticosteroid in 50%, proton pump inhibitors in 66%, elemental diet/ food elimination in 13% and systemic corticosteroid in 13%. Failure to thrive and abdominal pain in a male, atopic school-aged child was the most common feature of EE. Peripheral eosinophilia, high serum IgE and endoscopic esophageal erythema and trachealization should significantly raise the clinical index of suspicion for the diagnosis of EE.


The relationship of fatigue in breast cancer survivors with quality of life and factors to address in psychological interventions: A systematic review.
Severe fatigue occurs in one in four breast cancer survivors (BCS). Quality of life (QOL) and psychological factors are important in fatigue-oriented interventions for BCS, but an up-to-date overview is lacking. The aims of this review were to (i) provide a comprehensive overview of the relationship of fatigue with QOL and factors that can be addressed in psychological interventions for fatigue in BCS and (ii) determine the strength of evidence for these relationships. A systematic literature search was conducted to find studies on fatigue in BCS who had completed curative breast cancer treatment. Fatigue-related factors of 57 eligible studies were extracted and the level of evidence was determined. Factors regarding QOL (ie, general QOL, functioning, work ability, and mental health) had a negative relationship with fatigue (moderate to strong evidence). Target factors for psychological interventions were divided into the subcategories emotional problems, sleep disturbances, physical activity, pain, coping with cancer, dysfunctional cognitions, and social support. Moderate to strong evidence appeared for a relationship of fatigue with depressive symptoms, anxiety, distress, sleep disturbances, lower physical activity levels, pain, difficulties with coping with cancer, and catastrophizing about symptoms. These factors are points of attention for existing and future psychological interventions for fatigue in BCS.


[Evaluation of renal function: an update].
During the last years, GFR estimation has received substantial attention with a focus on comparing results of new formulas with GFR measurements, and standardization of creatinine assays. Calibration of creatinine should improve performances. However, frequently used equations have lower precision in high GFR populations. This is the reason why a continuous effort in improving predicting equations is still needed. The use of calibrated creatinine, the onset of new GFR markers such as cystatin C, and pooling data across many study populations are underway to develop better prediction.


Independent associations of physical activity and cardiorespiratory fitness with metabolic risk factors in children: the European youth heart study.
High levels of cardiorespiratory fitness (CRF) and physical activity (PA) are associated with a favourable metabolic risk profile. However, there has been no thorough exploration of the independent contributions of cardiorespiratory fitness and subcomponents of activity (total PA, time spent sedentary, and time spent in light, moderate and vigorous intensity PA) to metabolic risk factors in children and the relative importance of these factors. We performed a population-based, cross-sectional study in 9- to 10- and 15- to 16-year-old boys and girls from three regions of Europe (n = 1709). We examined the independent associations of subcomponents of PA and CRF with metabolic risk factors (waist circumference, BP, fasting glucose, insulin, triacylglycerol and HDL-cholesterol levels). Clustered metabolic risk was expressed as a continuously distributed score calculated as the average of the standardised values of the six subcomponents. CRF (standardised beta = -0.09, 95% CI -0.12, -0.06), total PA (standardised beta = -0.08, 95% CI -0.10, -0.05) and all other subcomponents of PA were significantly associated with clustered metabolic risk. After excluding waist circumference from the summary score and further adjustment for waist circumference as a confounding factor, the magnitude of the association between CRF and clustered metabolic risk was attenuated (standardised beta = -0.05, 95% CI -0.08, -0.02), whereas the association with total PA was unchanged (standardised beta = -0.08 95% CI -0.10, -0.05). PA and CRF are separately and independently associated with individual and clustered metabolic risk factors in children. The association between CRF and clustered risk is partly mediated or confounded by adiposity, whereas the association between activity and clustered risk is independent of adiposity. Our results suggest that fitness and activity affect metabolic risk through different pathways.


Fairness overrides reputation: the importance of fairness considerations in altruistic cooperation.
Behavioral findings in several strategic games indicate that people punish others if they think they are being treated unequally, even at the cost of minimizing their own material payoff. We investigated the primary driving force behind such non-self-regarding behavior, so-called, altruistic cooperation. In all of our studies, a mini ultimatum game was played either one-shot (in Experiment 1a and 1b) or repeatedly (Experiment 2), and rejections of inequitable distribution were taken as a measure of altruistic cooperation. In Experiment 1a, we replicated previous findings indicating that the key mechanism contributing to the emergence of altruistic cooperation is fairness considerations. In Experiment 1b, we delved into the relative importance of two aspects of fairness considerations (i.e., outcome fairness and intentions) and showed that both aspects were effective in determining the level of altruistic cooperation, with the contribution of intentions being more important. In Experiment 2, we investigated the effect of the opportunity for reputation building and future interaction on altruistic cooperation. We found that these factors became influential only when fairness considerations were weakened, particularly, as a result of the removal of the possible intentions behind an offer.


Introduction to optical methods for characterizing liquid crystals at interfaces.
This Instructional Review describes methods and underlying principles that can be used to characterize both the orientations assumed spontaneously by liquid crystals (LCs) at interfaces and the strength with which the LCs are held in those orientations (so-called anchoring energies). The application of these methods to several different classes of LC interfaces is described, including solid and aqueous interfaces as well as planar and nonplanar interfaces (such as those that define a LC-in-water emulsion droplet). These methods, which enable fundamental studies of the ordering of LCs at polymeric, chemically functionalized, and biomolecular interfaces, are described in this Instructional Review on a level that can be easily understood by a nonexpert reader such as an undergraduate or graduate student. We focus on optical methods because they are based on instrumentation that is found widely in research and teaching laboratories.


Who treats lung cancer? Results from a global survey.
In most Western nations, the medical oncologist plays a significant role in the administration of systemic therapy for lung cancer. In Japan however, treatment for lung cancer has historically been provided by pulmonologists and thoracic surgeons. A comparison of the management of advanced disease between Japan and other nations has not been described. An online, self-administered, international survey was sent to 3907 active members of the American Society of Clinical Oncology. Eligible participants were degreed physicians who prescribed systemic agents for adult cancer treatment within the past five years. In total, 281 respondents answered the questions regarding management of lung cancer. Thorough analysis demonstrated that pulmonologists play a significant role in Japan and the Netherlands, where the role of oncologic specialists is not well established. Of note, all the respondents from the Netherlands reported that pulmonary medicine primarily manages systemic chemotherapy in stage IV, adjuvant chemotherapy, and targeted therapy. We found there are several nations where non-oncologic specialists play a critical role in the systemic treatment of lung cancer. We expect this practice pattern to continue until the global adoption of the oncologic specialty role.


Improved charge carrier separation in barium tantalate composites investigated by laser flash photolysis.
Charge carrier dynamics in phase pure Ba5Ta4O15 and in a Ba5Ta4O15-Ba3Ta5O15 composite have been studied by means of diffuse reflectance laser flash photolysis spectroscopy in the presence and absence of an electron donor, in order to reveal the reason for the improved photocatalytic performance of the latter. For the first time the transient absorption of trapped electrons with a maximum at around 650 nm and of trapped holes with a transient absorption maximum at around 310 nm is reported for tantalates. The decay kinetics of the photogenerated charge carriers could be fitted by second order reaction kinetics, and the direct recombination of the trapped electrons with the trapped holes was proven. In the absence of an electron donor, no difference in the decay behavior between the phase pure material and the composite material is found. In the presence of methanol, for the pure phase Ba5Ta4O15 the recombination of the charge carriers could not be prevented and the trapped electrons also recombine with the ˙CH2OH radical formed via the methanol oxidation by the trapped holes. However, in the composite, the electron can be stored in the system, the ˙CH2OH radical injects an electron into the conduction band of the second component of the composite, i.e., Ba3Ta5O15. Thus, the electrons are available for an extended period to induce reduction reactions.


Image-guided therapy: evolution and breakthrough.
Beyond the advances made in computer-assisted interventions and robotic systems, the demand for more efficient and safer therapies remains challenging. Thus, if it is possible to improve the instrument tracking, steering, and target localization, to miniaturize the sensors and actuators, and to conduct preoperatively planned minimally invasive therapies, we still need new resources to achieve permanent destruction of abnormal tissues or suppression of pathological processes. Most of the physics-based (or energy-based) therapeutic principles at our disposal have been established a long time ago, but their actions on basic cellular and molecular mechanisms are not yet fully understood. They all have a wide spectrum of clinical targets in terms of organs and pathologies, modes of application (external, interstitial, intraluminal, etc.) with advantages and side-effect drawbacks, proven indications, and contraindications. Some of them may still face controversies regarding their outcomes. This short article, mainly focused on tumor destruction, briefly reviews in its first part some of these techniques and sketches the next generation under investigation. The former include radio frequency (RF), high-intensity focused ultrasound (HiFU), microwaves, and cryotherapy, of which all are temperature based. Laser-based approaches [e.g., photodynamic therapy (PDT) at large] are also discussed. Radiotherapy and its variants (hadrontherapy, brachytherapy, Gamma Knife, and CyberKnife) remain, of course, as the reference technique in cancer treatment. The next breakthroughs are examined in the second part of the article. They are based on the close association between imaging agents, drugs, and some stimulation techniques. The ongoing research efforts in that direction show that, if they are still far from clinical applications, strong expectations are made. From the point of view of interventional planning and image guidance, all of them share a lot of concerns.


The effect of ultrasound-guided serratus anterior plane block in addition to intrathecal morphine on early postoperative period after video-assisted thoracoscopic surgery.
The aim of this study was to evaluate the effect of serratus anterior plane block in addition to intrathecal morphine for early postoperative period after video-assisted thoracoscopic surgery on the amount of morphine consumption and the Visual Analog Scale scores. This single-blind, randomized-controlled study included a total of 64 patients (39 males, 25 females; mean age: 53.6±17.0 years; range, 20 to 89 years) who were scheduled for video-assisted thoracoscopic surgery in a tertiary hospital between September 2019 and March 2020. Postoperative pain control was achieved with intrathecal morphine 0.6 mg addition to serratus anterior plane block (Group ITM+SAPB) or with only intrathecal morphine (Group ITM) after an induction of anesthesia. The serratus anterior plane block was performed with a single injection of 0.4 mL/kg of 0.25% bupivacaine at the level of fifth rib with ultrasound guidance. Morphine consumption, pain scores, and side effects were recorded in the postoperative period. The mean morphine consumption was significantly lower in the ITM+SAPB group at all time points. Compared to the control group, the Visual Analog Scale-resting and coughing scores were significantly lower in the first 12 h after surgery. Pain scores were significantly higher in the ITM+SAPB group in patients where the trocar was inserted at upper level of the fifth rib than the lower level (3-5 vs. 5-8) during the first 6 h after surgery. The use of serratus anterior plane block in addition to intrathecal morphine is a safe and effective way to improve pain control for early postoperative period after video-assisted thoracoscopic surgery. The serratus anterior plane block ensures better analgesia until the peak effect of spinal morphine occurs.


The aggregate-forming pili (AFP) mediates the aggregative adherence of a hybrid-pathogenic Escherichia coli (UPEC/EAEC) isolated from a urinary tract infection.
Enteroaggregative Escherichia coli (EAEC) comprises an important diarrheagenic pathotype, while uropathogenic E. coli (UPEC) is the most important agent of urinary tract infection (UTI). Recently, EAEC virulence factors have been detected in E. coli strains causing UTI, showing the importance of these hybrid-pathogenic strains. Previously, we detected an E. coli strain isolated from UTI (UPEC-46) presenting characteristics of EAEC, e.g., the aggregative adherence (AA) pattern and EAEC-associated genes (aatA, aap, and pet). In this current study, we analyzed the whole genomic sequence of UPEC-46 and characterized some phenotypic traits. The AA phenotype was observed in cell lineages of urinary and intestinal origin. The production of curli, cellulose, bacteriocins, and Pet toxin was detected. Additionally, UPEC-46 was not capable of forming biofilm using different culture media and human urine. The genome sequence analysis showed that this strain belongs to serotype O166:H12, ST10, and phylogroup A, harbors the tet, aadA, and dfrA/sul resistance genes, and is phylogenetically more related to EAEC strains isolated from human feces. UPEC-46 harbors three plasmids. Plasmid p46-1 (~135 kb) carries some EAEC marker genes and those encoding the aggregate-forming pili (AFP) and its regulator (afpR). A mutation in afpA (encoding the AFP major pilin) led to the loss of pilin production and assembly, and notably, a strongly reduced adhesion to epithelial cells. In summary, the genetic background and phenotypic traits analyzed suggest that UPEC-46 is a hybrid strain (UPEC/EAEC) and highlights the importance of AFP adhesin in the adherence to colorectal and bladder cell lines.


Computer-Aided Evaluation of Blood Vessel Geometry From Acoustic Images.
A method for computer-aided assessment of blood vessel geometries based on shape-fitting algorithms from metric vision was evaluated. Acoustic images of cross sections of the radial artery and cephalic vein were acquired, and medical practitioners used a computer application to measure the wall thickness and nominal diameter of these blood vessels with a caliper method and the shape-fitting method. The methods performed equally well for wall thickness measurements. The shape-fitting method was preferable for measuring the diameter, since it reduced systematic errors by up to 63% in the case of the cephalic vein because of its eccentricity.


The peptide orphanin FQ inhibits beta-endorphin neurons and neurosecretory cells in the hypothalamic arcuate nucleus by activating an inwardly-rectifying K+ conductance.
Orphanin FQ (OFQ) is a novel heptadecapeptide whose structure resembles that of dynorphin A1-17. Its receptor shares appreciable homology with mu-, delta- and kappa-opioid receptors, and is highly expressed in the hypothalamus. The present study examined the effects of OFQ on neurons within the arcuate nucleus (ARC) of the mediobasal hypothalamus, using intracellular recordings from coronal slices. In current clamp, OFQ produced a hyperpolarization of ARC neurons, including those immunopositive for beta-endorphin, tyrosine hydroxylase and gonadotropin-releasing hormone. This hyperpolarization was dose-dependent, insensitive to antagonism by naloxone and was associated with a decrease in input resistance. In voltage clamp, OFQ produced an outward current associated with an increase in conductance. Varying the extracellular K+ concentration shifted the reversal potential for the OFQ response to the degree predicted by the Nernst equation. Furthermore, barium chloride markedly attenuated both the OFQ-induced hyperpolarization and decrease in input resistance. Administration of maximally effective concentrations of OFQ, followed by coadministration of maximal concentrations of either OFQ and the mu-opioid receptor agonist DAMGO or OFQ and the GABAB receptor agonist baclofen produced additive hyperpolarizations and outward currents. If DAMGO was applied first, followed by the coadministration of DAMGO and OFQ, then the responses were occluded. Taken together, these results indicate that OFQ inhibits beta-endorphin neurons, as well as A12 dopamine and GnRH neurosecretory cells, within the ARC by activating a subset of inwardly-rectifying K+ channels. This suggests that OFQ is not only an antiopioid peptide, but that it also modulates the hypothalamo-pituitary axis and, ultimately, reproductive behavior.


[Nasopharyngeal angiofibroma. Our experience (1990-2001)].
We present our experience in the treatment of nasopharyngeal angiofibromas, tumours not very common, with a benign histology but with the risk of severe epistaxis or possible involvement of vital structures. In a period of 12 years (1990-2001) we have treated 6 males with this pathology, operating 5 of them. We describe the clinical manifestations, the tumour stages following the Fisch classification, the diagnostic and surgical techniques used, the evolution of the patients and their postoperatory. We review also the literature about this subject.


Bridging population and tissue scale tumor dynamics: a new paradigm for understanding differences in tumor growth and metastatic disease.
To provide a better understanding of the relationship between primary tumor growth rates and metastatic burden, we present a method that bridges tumor growth dynamics at the population level, extracted from the SEER database, to those at the tissue level. Specifically, with this method, we are able to relate estimates of tumor growth rates and metastatic burden derived from a population-level model to estimates of the primary tumor vascular response and the circulating tumor cell (CTC) fraction derived from a tissue-level model. Variation in the population-level model parameters produces differences in cancer-specific survival and cure fraction. Variation in the tissue-level model parameters produces different primary tumor dynamics that subsequently lead to different growth dynamics of the CTCs. Our method to bridge the population and tissue scales was applied to lung and breast cancer separately, and the results were compared. The population model suggests that lung tumors grow faster and shed a significant number of lethal metastatic cells at small sizes, whereas breast tumors grow slower and do not significantly shed lethal metastatic cells until becoming larger. Although the tissue-level model does not explicitly model the metastatic population, we are able to disengage the direct dependency of the metastatic burden on primary tumor growth by introducing the CTC population as an intermediary and assuming dependency. We calibrate the tissue-level model to produce results consistent with the population model while also revealing a more dynamic relationship between the primary tumor and the CTCs. This leads to exponential tumor growth in lung and power law tumor growth in breast. We conclude that the vascular response of the primary tumor is a major player in the dynamics of both the primary tumor and the CTCs, and is significantly different in breast and lung cancer.


[Transobturator tape (Uratape). A new minimally invasive method in the treatment of urinary incontinence in women].
To evaluate the one-year results of transobturator suburethral tape for the treatment of female stress urinary incontinence. Suburethral tape was implanted via the transobturator technique. UraTape non-woven, non-elastic polypropylene tape with a 15 mm wide central (suburethral) silicone-coated zone was inserted without tension in a horizontal plane underneath the middle of the urethra from one obturator foramen to the other. The lateral ends of the tape were tunnelled percutaneously with a tunnelling device. The retropubic space was preserved and cystoscopy was not required. From May 2000 to February 2002, 32 patients with a mean age of 64 years (range: 50 to 81 years), suffering from stress urinary incontinence without associated prolapse, were operated by the same surgeon (ED). All patients were evaluated before the operation by clinical and urodynamic examination: 5 patients presented sphincter incompetence (maximum closing pressure < 20 cmH2O); five patients presented recurrent urinary incontinence after Burch or TVT; 18 patients presented mixed incontinence and detrusor instability was demonstrated on cystometry in 6 of them. The results were evaluated by two independent doctors (clinical examination, uroflowmetry, cough test). Voiding disorders suggestive of bladder outflow obstruction were defined by the presence of the following two criteria: Qmax < 15 ml/s, residual volume > 20%. The mean follow-up of the study was 17 months (range: 13 to 29 months). The mean operating time was 15 minutes. No intraoperative complication was observed. One patient presented complete postoperative bladder retention that resolved after 4 weeks of self-catheterization. 29/32 patients (90.6%) were cured and 3/32 (9.4%) were improved. No urethral erosions were observed. No residual pain and no functional impairment related to the tape was observed. 5/32 patients presented voiding disorders suggestive of bladder outflow obstruction. Two patients developed de novo urge incontinence. Transobturator Uratape is a simple and effective procedure with a follow-up of one year for the treatment of female stress urinary incontinence. The transobturator approach avoids the risks of bladder, intestinal and vascular injuries. Evaluation of the results with a longer follow-up is necessary to validate this technique.


Contribution of frontal cerebral blood flow measured by (99m)Tc-Bicisate spect and executive function deficits to predicting treatment outcome in alcohol-dependent patients.
To determine whether inhibition and working memory deficits, and reduced regional cerebral blood flow (rCBF) (previously shown to be related), measured at the end of a detoxification programme, predict alcoholic relapse 2 months later. Twenty uncomplicated alcoholic inpatients were investigated at the end of detoxification, at least 7 days since the last dose of diazepam, and a mean of 18.8 days since the last drink. Their performance was assessed on the inhibition (Hayling) test, working memory (Alpha-span task), episodic memory (California Verbal Learning Test) and abstract reasoning (Progressive Matrices). Frontal CBF was assessed at the same time with a semiquantitative (99m)Tc-Bicisate SPECT procedure. Patients were contacted 2 months later. Patients who abstained (n = 9) did not differ from those who relapsed (n = 11) on age, gender, smoking, duration of alcohol misuse, number of previous detoxifications, amount of ethanol consumed the month prior to admission to the detoxification programme, state anxiety, trait anxiety, or depression. Relapsed subjects had shown a lower uptake of (99m)Tc-Bicisate in the bilateral medial frontal gyrus (n = 9; mean ratio +/- SD = 0.69 +/- 0.006) than abstainers (n = 11; 0.85 +/- 0.19), and poorer performance on the Alpha-span task and the Hayling test. The other tests were not different. Inhibition and working memory deficits, associated with low levels of CBF in the medial frontal gyrus, are related to the difficulty of maintaining short-term abstinence from alcohol.


Laboratory study to assess causative factors affecting temporal changes in filtering facepiece respirator fit: part I - pilot study.
The National Institute for Occupational Safety and Health is conducting a first-of-its-kind study that will assess respirator fit and facial dimension changes as a function of time and improve the scientific basis for decisions on the periodicity of fit testing. A representative sample of 220 subjects wearing filtering-facepiece respirators (FFR) will be evaluated to investigate factors that affect changes in respirator fit over time. The objective of this pilot study (n = 10) was to investigate the variation in fit test data collected in accordance with the study protocol. Inward leakage (IL) and filter penetration were measured for each donned respirator, permitting the calculation of face seal leakage (FSL) and fit factor (FF). The study included only subjects who (a) passed one of the first three fit tests (FF ≥ 100), and (b) demonstrated through a series of nine donnings that they achieved adequate fit (90th percentile FSL was ≤ 0.05). Following the respirator fit tests, 3-D scans of subjects were captured, and height, weight, and 13 traditional anthropometric facial dimensions were measured. The same data were collected 2 and 4 weeks after baseline. The mean change in FSL for the 10 subjects was 0.044% between Visits 1 and 2, and was 0.229% between Visits 1 and 3. Technicians achieved at least moderate reliability for all manual measurements except nose protrusion. Filter penetration was generally less than 0.03%. Geometric mean fit factors were not statistically different among the three visits. The large variability was observed with different respirator samples for the same model, between subjects (inter), and within each subject (intra). Although variability was observed, adequate fit was maintained for all 10 subjects. Pilot scans collected show subject faces remained the same over the 4 weeks. The consistent results during the pilot study indicate that the methods and procedures are appropriate for the 3-year main study. In addition, this baseline fit change data will be compared with future fit changes to determine if the changes are meaningful.


Preparation of pH-sensitive alginate-based hydrogel by microfluidic technology for intestinal targeting drug delivery.
Hydrogel microspheres stand out in drug delivery due to their small particle size, biocompatibility and good internal stability. In this paper, pH-sensitive hydrogels are prepared by microfluidic technology for targeted drug delivery in the small intestine. A coaxial dual-channel microfluidic chip is constructed. By analyzing the effects of flow rates and three fracture stages (Rayleigh-Plateau instability crushing stage, pressure difference crushing stage and shear force crushing stage) on the size of hydrogel microspheres, the optimal control stage of the microsphere size is determined (shear force crushing stage). Based on this, the accurate control model of the hydrogel microsphere size is proposed. In addition, based on the coaxial dual channel microfluidic chip, a monolayer hydrogel microcapsule loaded with Indometacin is prepared. The core-shell hydrogel microcapsules loaded with Indometacin are prepared by an improved coaxial three channel microfluidic chip. The swelling rates of both microcapsules in simulated intestinal fluid are significantly higher than those in simulated gastric fluid. The results of in vitro simulated release experiments show that the two hydrogel microcapsules basically do not release in simulated gastric juice. In simulated intestinal fluid, single-layer hydrogel microcapsules show rapid release, while core-shell hydrogel microcapsules showed slow release. In conclusion, the alginate-based hydrogel microcapsules have good stability and pH sensitivity, and are suitable for targeted drug delivery in the small intestine.


PTM-Shepherd: Analysis and Summarization of Post-Translational and Chemical Modifications From Open Search Results.
Open searching has proven to be an effective strategy for identifying both known and unknown modifications in shotgun proteomics experiments. Rather than being limited to a small set of user-specified modifications, open searches identify peptides with any mass shift that may correspond to a single modification or a combination of several modifications. Here we present PTM-Shepherd, a bioinformatics tool that automates characterization of post-translational modification profiles detected in open searches based on attributes, such as amino acid localization, fragmentation spectra similarity, retention time shifts, and relative modification rates. PTM-Shepherd can also perform multiexperiment comparisons for studying changes in modification profiles, e.g., in data generated in different laboratories or under different conditions. We demonstrate how PTM-Shepherd improves the analysis of data from formalin-fixed and paraffin-embedded samples, detects extreme underalkylation of cysteine in some data sets, discovers an artifactual modification introduced during peptide synthesis, and uncovers site-specific biases in sample preparation artifacts in a multicenter proteomics profiling study.


Treatment of autoimmune disease by adoptive cellular gene therapy.
Autoimmune disorders represent inappropriate immune responses directed at self-tissue. Antigen-specific CD4+ T cells and antigen-presenting dendritic cells (DCs) are important mediators in the pathogenesis of auto-immune disease and thus are ideal candidates for adoptive cellular gene therapy, an ex vivo approach to therapeutic gene transfer. Using retrovirally transduced cells and luciferase bioluminescence, we have demonstrated that primary T cells, T cell hybridomas, and DCs rapidly and preferentially home to the sites of inflammation in animal models of multiple sclerosis, arthritis, and diabetes. These cells, transduced with retroviral vectors to drive expression of various "regulatory proteins" such as IL-4, IL-10, IL-12p40, and anti-TNF scFv, deliver these immunoregulatory proteins to the inflamed lesions, providing therapy for experimental autoimmune encephalitis (EAE), collagen-induced arthritis (CIA), and nonobese diabetic mice (NOD).


Co-Efficient Vector Based Differential Distributed Quasi-Orthogonal Space Time Frequency Coding.
Distributed space time frequency coding (DSTFC) schemes address problems of performance degradation encountered by cooperative broadband networks operating in highly mobile environments. Channel state information (CSI) acquisition is, however, impractical in such highly mobile environments. Therefore, to address this problem, designers focus on incorporating differential designs with DSTFC for signal recovery in environments where neither the relay nodes nor destination have CSI. Traditionally, unitary matrix-based differential designs have been used to generate the differentially encoded symbols and codeword matrices. Unitary based designs are suitable for cooperative networks that utilize the amplify-and-forward protocol where the relay nodes are typically required to forego differential decoding. In considering other scenarios where relay nodes are compelled to differentially decode and re-transmit information signals, we propose a novel co-efficient vector differential distributed quasi-orthogonal space time frequency coding (DQSTFC) scheme for decode-and-forward cooperative networks. Our proposed space time frequency coding scheme relaxes the need for constant channel gain in the temporal and frequency dimensions over long symbol periods; thus, performance degradation is reduced in frequency-selective and time-selective fading environments. Simulation results illustrate the performance of our proposed co-efficient vector differential DQSTFC scheme under different channel conditions. Through pair-wise error probability analysis, we derive the full diversity design criteria for our code.


Synthesis and characterization of CaCO3-biopolymer hybrid nanoporous microparticles for controlled release of doxorubicin.
Doxorubicin (Dox) is a hydrophilic drug extensively used for treatment of breast, lung, and ovarian cancer, among others; it is highly toxic and can cause serious side effects on nontargeted tissues. We developed and studied a hybrid nanoporous microparticle (hNP) carrier based on calcium carbonate and biopolymers derivatized with folic acid (FA) and containing Dox as a chemotherapeutic drug model. The hNPs were characterized by X-ray diffraction, and Raman and Fourier transform infrared (FTIR) spectroscopies. The X-ray diffraction patterns of calcium carbonate particles showed about 30-70% vaterite-calcite polymorphisms and up to 95% vaterite, depending on the absence or the presence of biopolymers as well as their type. Scanning electron microcopy images revealed that all types of hNPs were approximately spherical and porous with average diameter 1-5 μm, and smaller than CaCO3 microparticles. The presence of biopolymers in the matrices was confirmed after derivatization with a fluorescein isothiocyanate probe by means of confocal microscopy and FTIR synchrotron beamline analysis. In addition, the coupling of lambda carrageenan (λ-Car) to FA in the microparticles (FA-λ-Car-hNPs) increased the cancer-cell targeting and also extended the specific surface area by up to ninefold (26.6 m2 g(-1)), as determined by the Brunauer-Emmett-Teller isotherm. A nanostructured porous surface was found in all instances, and the FA-λ-Car-hNP pore size was about 30 nm, as calculated by means of the Barrett-Joyner-Halenda adsorption average. The test of FA-λ-Car-hNP anticancer activity on human osteosarcoma MG-63 cell line showed cell viabilities of 13% and 100% with and without Dox, respectively, as determined by crystal violet staining after 24 h of incubation.


Flavonoids with hepatoprotective activity from the leaves of Cleome viscosa L.
One new flavonol glycoside named visconoside C (1), together with seven known flavonol glycosides, quercetin 3-O-β-d-glucopyranoside 7-O-α-l-rhamnopyranoside (2), quercetin 7-O-α-l-rhamnopyranoside (3), astragalin (4), kaempferol 3-O-(4-O-acetyl)-α-l-rhamnopyranoside (5), kaempferol 7-O-α-l-rhamnopyranoside (6), kaempferitrin (7) and kaempferol 3-O-β-d-glucopyranoside 7-O-α-l-rhamnopyranoside (8) were isolated by various chromatography methods from the leaves of Cleome viscosa L. Their structures were elucidated by IR, UV, HR-ESI-MS and NMR (1D & 2D) experiments. The cytotoxicity and hepatoprotective activities using HepG2 human hepatoma cell line of 1 were measured by MTT assay. At the concentration of 25 μM and 50 μM, 1 showed cytotoxic activity against HepG2 cells (cell viability was decreased to 22.2 and 23.0%, respectively, compared with doxorubicin control), while at the concentration of 100 μM, 1 showed hepatoprotective activity against CCl4-induced hepatotoxicity on HepG2 cells (34.3%, compared with quercetin control).


HELLP syndrome.
HELLP syndrome is a serious, life-threatening form of pre-eclampsia with a typical laboratory triad. The incidence of the disease is reported as being 0.17-0.85% of all live births. There has been, to date, neither reliable early recognition nor effective prevention of HELLP syndrome. As a result of endothelial dysfunction, activation of intravascular coagulation occurs with fibrin deposition in the capillaries and consecutive microcirculation disorders. The disease manifests itself on average between 32-34 weeks' gestation. HELLP syndrome will occur postpartum in up to 30% of the cases. The clinical cardinal symptom of the disease is right upper quadrant pain or epigastric pain accompanied with nausea, vomiting and malaise. In 20% of the cases with HELLP syndrome there is no hypertension and 5-15% of the pregnant patients present a low level of proteinuria or none at all. The early recognition of hemolysis is most sensitively managed by the determination of the serum haptoglobin. The increase of the aspartate transaminase (AST) and the alanine transaminase (ALT) often precedes a decrease in platelets. The course of HELLP syndrome is incalculable. It is universally agreed that a pregnancy from 32-34 weeks should be immediately delivered. Before 32-34 weeks, expectant management is generally possible in a perinatal center. The frequency for a repeated hypertensive disease in pregnancy ranges from 27% to 48%.


Recognizing Clothes Patterns for Blind People by Confidence Margin based Feature Combination.
Clothes pattern recognition is a challenging task for blind or visually impaired people. Automatic clothes pattern recognition is also a challenging problem in computer vision due to the large pattern variations. In this paper, we present a new method to classify clothes patterns into 4 categories: stripe, lattice, special, and patternless. While existing texture analysis methods mainly focused on textures varying with distinctive pattern changes, they cannot achieve the same level of accuracy for clothes pattern recognition because of the large intra-class variations in each clothes pattern category. To solve this problem, we extract both structural feature and statistical feature from image wavelet subbands. Furthermore, we develop a new feature combination scheme based on the confidence margin of a classifier to combine the two types of features to form a novel local image descriptor in a compact and discriminative format. The recognition experiment is conducted on a database with 627 clothes images of 4 categories of patterns. Experimental results demonstrate that the proposed method significantly outperforms the state-of-the-art texture analysis methods in the context of clothes pattern recognition.


[Change in sexual desire in the menopausal woman: a succinct evaluation].
Physicians or gynecologists, specifically in their general practice or in the setting of a menopause clinic, are more and more frequently confronted with sexual complaints of menopausal women. Among these, decline in sexual desire is probably the most usually reported. The first study to evaluate a potential relationship between sexual functioning and menopause was conducted by Hallström in 1977. Thereafter, a review of the literature was able to show that there is nearly a consensus regarding the role of estrogens in that condition. They effectively relieve vaginal atrophy and resulting dyspareunia. There is less agreement, however, regarding a direct effect of estrogens on more complex sexual behavior and motivation. When analyzing potential influence of sex hormones, estrogens may exert a positive effect on the quality of the sexual relationship whereas androgens can definitely increase sexual "motivation" including sexual desire. In spite of the potentially important part played by androgens as promoters of libido and in the maintenance of sexual functioning in men and women, the exact role of the hormonal treatment in releaving sexual complaints still remains controversial. In some women where decline of sexual desire can be reasonably attributed to menopause, androgens in non-masculinizing adequate dosages, can be effectively included in the postmenopausal hormone replacement regimen. However, etiology of diminished sexual motivation and desire is far from univocal particularly in the human being where psychological, social and cultural influences are endowed with a prominent importance. It is accordingly quite conspicuous that our sexual life is not reduced to hormonal fluctuations only. A short critical review of the literature devoted to the main aspects of changes of sexual desire associated with menopause is presented.


Machine-learned Adaptive Switching in Voluntary Lower-limb Exoskeleton Control: Preliminary Results.
Lower-limb exoskeletons utilize fixed control strategies and are not adaptable to user's intention. To this end, the goal of this study was to investigate the potential of using temporal-difference learning and general value functions for predicting the next possible walking mode that will be selected by users wearing exoskeletons in order to reduce the effort and cognitive load while switching between different modes of walking. Experiments were performed with a user wearing the Indego exoskeleton and given the authority to switch between five walking modes that were different in terms of speed and turn direction. The user's switching preferences were learned and predicted from device-centric and room-centric measurements by considering similarities in the movements being performed. A switching list was updated to show the most probable future next modes to be selected by the user. In contrast to other approaches that either can only predict a single time-step or require intensive offline training, this work used a computationally inexpensive method for learning and has the potential of providing temporally extended sets of predictions in real-time. Comparing the number of required manual switches between the machine-learned switching list and the best possible static lists showed an average decrease of 42.44% in the required switches for the machine-learned adaptive strategy. These promising results will facilitate the path for real-time application of this technique.


The effect of nocturnal patient care interventions on patient sleep and satisfaction with nursing care in neurosurgery intensive care unit.
Sleep disturbance in an intensive care unit is a common problem. One of the main factors causing sleep disturbances in an intensive care unit is nocturnal patient care interventions. This study aims to determine the impact of patient care interventions performed at night in a neurosurgical intensive care unit on patients' sleep and their nursing care satisfaction. The descriptive study was conducted on 82 patients in a neurosurgical intensive care unit between January 2009 and March 2010. The data were collected by data collection instruments and Newcastle Satisfaction with Nursing Scales. The data were statistically analyzed by frequency, mean, standard deviation, chi-square, and Mann-Whitney U test. The study showed that 53.7% of the patients experienced sleep disturbances in the neurosurgical intensive care unit. Because of nursing interventions at night, 39.1% of these patients had their sleep affected, but this problem did not cause any negative impact on the patients' satisfaction (Newcastle Satisfaction with Nursing Scales score = 88.21 ± 9.83). The patients received, on average, 42.21 ± 7.45 times patient care interventions at night; however, the frequency of patient care interventions at night showed no effect on sleep disturbances in this study (p > .05). The most frequently given patient care interventions were, respectively, vital signs monitoring, neurological assessment, and repositioning in bed. These interventions were performed commonly at 6 a.m., 12 a.m., and 7 p.m. In this study, despite the patients reporting sleep disturbances in the neurosurgical intensive care unit because of nocturnal patient care interventions that prevented them from sleeping, the patients' satisfaction on the given nursing care was not negatively impacted. To reduce sleep disturbances because of nursing care initiatives and promote uninterrupted sleep in the intensive care unit, it can be useful to develop new protocols regulating night care activities.


Exploring Route-Specific Pharmacokinetics of PFAS in Mice by Coupling in Vivo Tests and Physiologically Based Toxicokinetic Models.
Oral ingestion, inhalation, and skin contact are important exposure routes for humans to uptake per- and polyfluoroalkyl substances (PFAS). However, nasal and dermal exposure to PFAS remains unclear, and accurately predicting internal body burden of PFAS in humans via multiple exposure pathways is urgently required. We aimed to develop multiple physiologically based toxicokinetic (PBTK) models to unveil the route-specific pharmacokinetics and bioavailability of PFAS via respective oral, nasal, and dermal exposure pathways using a mouse model and sought to predict the internal concentrations in various tissues through multiple exposure routes and extrapolate it to humans. Mice were administered the mixed solution of perfluorohexane sulfonate, perfluorooctane sulfonate, and perfluorooctanoic acid through oral, nasal, and dermal exposure separately or jointly. The time-dependent concentrations of PFAS in plasma and tissues were determined to calibrate and validate the individual and combined PBTK models, which were applied in single- and repeated-dose scenarios. The developed route-specific PBTK models successfully simulated the tissue concentrations of PFAS in mice following single or joint exposure routes as well as long-term repeated dose scenarios. The time to peak concentration of PFAS in plasma via dermal exposure was much longer (34.1-83.0 h) than that via nasal exposure (0.960 h). The bioavailability of PFAS via oral exposure was the highest (73.2%-98.0%), followed by nasal (33.9%-66.8%) and dermal exposure (4.59%-7.80%). This model was extrapolated to predict internal levels in human under real environment. Based on these data, we predict the following: PFAS were absorbed quickly via nasal exposure, whereas a distinct hysteresis effect was observed for dermal exposure. Almost all the PFAS to which mice were exposed via gastrointestinal route were absorbed into plasma, which exhibited the highest bioavailability. Exhalation clearance greatly depressed the bioavailability of PFAS via nasal exposure, whereas the lowest bioavailability in dermal exposure was because of the interception of PFAS within the skin layers. https://doi.org/10.1289/EHP11969.


Acquired and congenital risk factors associated with cerebral venous sinus thrombosis.
The mechanistic paradigm underlying venous thrombosis at atypical locations stems from the observation that most events occur as a result of pathology of the organ system drained by the involved venous segment. Cerebral venous sinus thrombosis stands apart as an exception to this general rule. Although brain and sinus pathology are well established causes, these combined variables account for approximately one third of cases. The marked female preponderance and strong association with gender specific risk factors including hormonal manipulation, pregnancy and the puerperium are particularly notable. Factor V Leiden and prothrombin G20210A mutations and hyperhomocysteinemia represent important risk factors particularly when combined with acquired variables. The association with oral contraception use and the prothrombin G20210A gene mutation may offer insights into the anatomic predilection for cerebral venous sinus involvement as compared to venous thrombosis of the lower extremities. The intent of this review is to summarize the corporate literature of both acquired and congenital risk factors associated with cerebral venous sinus thrombosis in order to assist clinicians in their search for underlying mechanisms and to risk stratify patients for anticoagulation treatment duration and risk of recurrent thrombosis.


Interventions for Children with Neurocognitive Impairments in Resource-Limited Settings: A Systematic Review.
Many children and adolescents around the world suffer from neurocognitive deficits due to chronic disorders, such as Human Immunodeficiency Virus (HIV) and malaria. Resource-limited settings exacerbate the risk of negative cognitive outcomes due to high prevalence of associated disorders, poverty, and limited access to interventions. Current literature does not provide consensus regarding the efficacy of interventions to support children with cognitive impairments in low-resource settings. This research aimed to identify and evaluate interventions for youth with neurocognitive deficits in resource-limited settings. A systematic review of peer-reviewed literature was conducted within five databases (PubMed, Web of Science, CINAHL, PsycInfo, and WHO Index Medicus). Cognitive impairment was broadly defined to be inclusive of aspects of intellectual and cognitive functioning (e.g., working memory, attention, executive function). The income status of the country or countries in which each study was located was determined according to World Bank Income Status. Studies conducted in countries classified as low- or middle-income were included. Since low-resource areas exist within high-income countries, the resource availability within study settings in high-income countries was systematically evaluated for inclusion. The search yielded 19 articles that met all inclusion criteria. Interventions included strategies involving caregiver training, computerized and non-computerized cognitive training, physical activity, and nutritional supplementation. Interventions were administered in medical facilities, educational facilities, or the home. The majority of the interventions targeted the domains of memory and attention. Overall, the efficacy of interventions was inconsistent. Further, results indicated that the relationship between cognitive improvement and intervention types was not consistent across cognitive domains. However, when evaluating studies on an individual basis, some strategies demonstrated clinically- and statistically-significant improvement in cognitive function among specific groups of children. The low article yield highlights that few researchers have evaluated pediatric cognitive support interventions in low-resource contexts. This review suggests support strategies that should be considered for future studies as neurocognitive screening capacity improves in resource-limited settings.


Studies on early association of Salmonella typhimurium with intestinal mucosa in vivo and in vitro: relationship to virulence.
The abilities of six strains of Salmonella typhimurium to associate with rabbit ileal mucosa have been measured in vitro. Two were "virulent" strains (TML and W118 which are invasive and inducers of fluid secretion in rabbit ileal loops); four were "avirulent" (LT7, M206 and SL1027 which are invasive but induce negligible fluid secretion, and Thax-1 which is neither invasive nor an inducer of fluid secretion). A special organ-culture apparatus was designed to expose only the luminal surface of the mucosa to organisms. Viable counts of washed homogenised tissue taken 30 min after challenge showed that virulent strains TML and W118 and avirulent strains LT7 and M206 could not be distinguished from each other. Avirulent strain SL1027 associated less well than the other four strains, and Thax-1 associated less well than SL1027; both these strains were non-motile whereas the other four were motile. Thus, early association with gut mucosa did not discriminate all avirulent strains from the virulent strains. Qualitative examination of tissues by scanning electronmicroscopy did not detect strains LT7 and M206 on the mucosal surface whereas strains TML and W118 were readily seen, suggesting that the nature of association of virulent and avirulent strains was different. Qualitative examination by transmission electronmicroscopy of tissues challenged in vivo for 120 min showed virulent strains TML and W118 invading epithelial cells; similar events were reproduced after 120-min challenge in vitro. In contrast, invasion by avirulent strains was observed only very rarely.


Outbreak of candidemia caused by fluconazole resistant Candida parapsilosis strains in an intensive care unit.
Candidemia is an increasing problem in tertiary care hospitals worldwide. Here, we report the first outbreak of candidemia caused by fluconazole-resistant C. parapsilosis (FRCP) strains in Brazil. This was a cross-sectional study of clinical and microbiological data of all candidemic episodes diagnosed from July 2011 to February 2012 in a 200-bed tertiary care hospital. Initial yeast identification and susceptibility testing were performed using the VITEK 2 - System. Isolates of Candida spp. resistant to fluconazole were sent to a reference laboratory (LEMI-UNIFESP) for further molecular identification and confirmation of resistance by CLSI microdilution test. A multivariate analysis was conducted to identify factors associated with FRCP infection. We identified a total of 40 critically ill patients with candidemia (15 women) with a median age of 70 years. The incidence of candidemia was 6 cases/1,000 patients admissions, including 28 cases (70 %) of infection with C. parapsilosis, 21 of which (75 %) were resistant to fluconazole. In only 19 % of FRCP candidemia cases had fluconazole been used previously. The results of our study indicated that diabetes is a risk factor for FRCP candidemia (p = 0.002). Overall, mortality from candidemia was 45 %, and mortality from episodes of FRCP infections was 42.9 %. The clustering of incident cases in the ICU and molecular typing of strains suggest horizontal transmission of FRCP. Accurate vigilant monitoring for new nosocomial strains of FRCP is required.


Expression and function of histamine receptors in human monocyte-derived dendritic cells.
Histamine is a well-known mediator eliciting different responses in immune and nonimmune cells, but its role in modulating dendritic cell (DC) functions has been marginally investigated. The purpose of this investigation was to analyze whether human monocyte-derived DCs express functional histamine receptors according to their maturation stage. DCs were derived from monocytes and used as immature or LPS-differentiated cells. DCs were tested for histamine receptor expression, chemotaxis, cytokine release, and the capacity to induce T-cell differentiation in response to specific histamine receptor agonists. Immature and mature DCs expressed the mRNA for H1, H2, and H3 histamine receptors. Histamine induced intracellular Ca2+ transients, actin polymerization, and chemotaxis in immature DCs. Maturation of DCs resulted in the loss of these responses. In maturing DCs, however, histamine dose-dependently enhanced intracellular cAMP levels and stimulated IL-10 secretion while inhibiting production of IL-12. As a consequence, histamine might contribute to the impairment of generation of allogeneic type 1 responses via maturing DCs. Specific histamine receptor agonists or antagonists revealed that Ca2+ transients, actin polymerization, and chemotaxis of immature DCs were due to stimulation of H1 and H3 subtypes. Modulation of IL-12 and IL-10 secretion by histamine involved the H2 and H3 receptors exclusively. Our study suggests that histamine has important biological effects on DC activities, opening the possibility that histamine released during inflammatory or immune responses could regulate DC functions and ultimately favor type 2 lymphocyte-dominated immunity.


Association between growth factor heregulin1α and receptors in growth of ovarian cancer cell line with high potentiality of peritoneal dissemination.
Ovarian cancer, one of the poor-prognosis gynecological malignancies, is often associated with extensive peritoneal carcinomatosis when initially treated. The mechanism of the formation of peritoneal carcinomatosis from ovarian cancer is still unknown. It has been reported that overexpression of cancer-related growth factors and/or receptors may worsen the prognosis of diseases. In the previous paper, we had established the human ovarian serous adenocarcinoma cell lines from those with no potentiality of peritoneal dissemination (FOC-3) to high potentiality (MFOC-3), however, the mechanism of its phenotypical change remains unknown. In this paper, we compared these two cell lines for growth potential and the expression of growth factor heregulin (HRG)-1α and HER-2, HER-3, and HER-4 receptors. In addition, the effect of anti-receptor antibodies on cell growth was investigated. RT-PCR and Western blot analysis found the promotion of the expression of HRG precursor and HRG-1α in MFOC-3. Examination of the number of growing cells over time revealed a statistically significant increase in the number of cells in MFOC-3 compared with FOC-3. In a study using the addition of exogenous HRG-1α, no changes were observed in FOC-3 while statistically significant cell growth was noted in MFOC-3. In a growth inhibition study, statistically significant cell growth inhibition was achieved with the addition of anti-HER2 receptor antibody. Taken together, the results of this study suggested that HRG may play an important role in the increased growth potential of peritoneal dissemination of ovarian cancer. In particular, HER-2 receptors that can act as a starting point to trigger intracellular signaling pathways are strongly involved in the progression of cancer. Therefore, molecular target drug therapies blocking the HER-2 receptor are promising candidates for ovarian cancer treatment in the future.


Medication errors and drug-dispensing systems in a hospital pharmacy.
Pharmacies permeate and interconnect various actions developed in different sectors within the complex process of the use of drugs in a hospital. Dispensing failures mean that a breach has occurred in one of the last safety links in the use of drugs. Although most failures do not harm patients, their existence suggests fragility in the process and indicates an increased risk of severe accidents. Present concepts on drug-related incidents may be classified as side effects, adverse effects, and medication errors. Among these are dispensing errors, usually associated with poor safety and inefficient dispensing systems. Factors associated with dispensing errors may be communication failures, problems related to package labels, work overload, the physical structure of the working environment, distraction and interruption, the use of incorrect and outdated information sources and the lack of patient knowledge and education about the drugs they use. So called banal dispensing errors reach significant epidemiological levels. The purpose of this paper, which is part of a study on the occurrence of dispensing errors in the pharmacy of a large hospital, is to review the main concepts that guide studies on adverse effects and to provide an update on dispensing errors.


Studies on cadmium toxicity in plants: a review.
This review emphasises cadmium toxicity on plants with regards to ecological, physiological and biochemical aspects. Cadmium toxicity in plants and problems concerning tolerance and ecological performance are discussed briefly. Efforts have been made to compare the relative sensitivity of various plant groups including micro-and macro-flora. This review may help in interdisciplinary studies to assess the ecological significance of metal stress.


[25-hydroxycholecalciferol and 24,25-dihydroxycholecalciferol content on rat tissues in vitamin D poisoning].
As vitamin D3 dose increases, the level of 25-hydroxycholecalciferol in the blood plasma, liver, kidneys, small intestine, bones and muscles of rats rises. The maximum concentration and maximum content of 25-hydroxycholecalciferol with reference to the entire tissue growing with vitamin D3 dose increase are characteristic for the osteal tissue. The synthesis of excess quantities of 25-hydroxycholecalciferol is followed by formation of a metabolite that is similar to 24,25-dioxycholecalciferol from the standpoint of chromatographic mobility. The metabolite is accumulated in the kidneys, intestine, blood plasma and to a less measure in the osteal tissue. No metabolite could be detected in the liver or muscles.


Comparative study of acute effects of albuterol and isoproterenol sulphate aerosols in bronchial asthma.
Albuterol, a new bronchodilator drug known to cause beta2-adrenergic receptor stimulation, was compared with isoproterenol sulphate for their pulmonary and cardiovascular effects in patients suffering from bronchial asthma. In a double-blind manner 24 patients received as aerosol 170 micrograms of Albuterol or 150 micrograms of Isoproterenol or placebo on three different days. Spirometric, plethysmographic, heart rate and blood pressure measurements were made at 1, 5, 15, 30, 60, 90, 120, 300 and 360 minutes after drug inhalation. Baseline values for the various indices were not significantly different before administration of the drugs. Results demonstrate that Albuterol is an effective bronchodilator and its bronchodilating effect is significantly superior and of longer duration than that of Isoproterenol. Albuterol did not produce any significant changes in blood pressure and pulse rate, thus confirming its selectivity for beta2 receptors.


Evaluation of renal values during treatment for heartworm disease in 27 client-owned dogs.
Canine heartworm disease (CHD) caused by Dirofilaria immitis remains a common preventable disease with increasing incidence in some parts of the USA. The treatment guidelines of the American Heartworm Society (AHS) currently recommend monthly macrocyclic lactone administration, 28 days of doxycycline given orally every 12 h and three injections of melarsomine dihydrochloride (1 injection on day 2 of treatment followed 30 days later by 2 injections 24 h apart). Minocycline has also been utilized when doxycycline is unavailable. The systemic effects of CHD, which particularly impact cardiac and renal function, have been described, with infected dogs often experiencing renal damage characterized by an increase in serum concentrations of renal biomarkers. Although the AHS treatment protocol for CHD has been shown to be safe and effective in most cases, the potential for complications remains. No study as of yet has evaluated changes in symmetric dimethylarginine (SDMA), a sensitive marker of renal function, during treatment for CHD. The purpose of the present study was to evaluate renal function in dogs by measuring serum creatinine and SDMA concentrations during the adulticide treatment period. Serum creatinine and SDMA concentrations were measured in 27 client-owned dogs affected by CHD at the following time points: prior to starting doxycycline or minocycline therapy (baseline), during doxycycline or minocycline therapy (interim), at the time of the first dose of melarsomine (first dose), at the time of the second dose of melarsomine (second dose) and at the dog's follow-up visit after treatment, occurring between 1 and 6 months after completion of therapy (post-treatment). Concentrations of creatinine and SDMA were compared between time points using a mixed effects linear model. Mean SDMA concentrations following the second dose of melarsomine were significantly lower (-1.80 ug/dL, t-test, df = 99.067, t = -2.694, P-Value = 0.00829) than baseline concentrations. There were no other statistically significant differences in the concentration of either biomarker between the baseline and the other time points in CHD dogs undergoing treatment. The results suggest that the current AHS protocol may not have a substantial impact on renal function.


Acute behavioural disturbances related to imaging studies and outcome in mild-to-moderate head injury.
The frequency of behavioural disturbances early after injury in relation to outcome was prospectively investigated in a series of 67 patients with mild-to-moderate head injury (as defined by GCS on admission). In more than half of the patients, behavioural disturbances were observed. Restlessness occurred in 40% of patients, whereas agitation was seen in 19% of patients. In all patients, restlessness and agitation disappeared before resolution of PTA. In multiple regression analysis, restlessness and PTA were found to be separate factors in predicting outcome. On imaging studies, twice as many lesions were seen in patients with restlessness and agitation (81% compared to 39%), mainly localized in the frontotemporal region. In two thirds of patients with early behavioural disturbances, residual emotional and cognitive impairments were seen 1 year after injury. This study suggests that behavioural disturbances in the early phase after injury are related to frontotemporal lesions and lends support for the view of the existence of a separate profile of patient behaviour in mild-to-moderate head injury.


On rising medical student debt: in for a penny, in for a pound.
Using national databases of the Association of American Medical Colleges, the authors have examined reasons for the rising indebtedness of U.S. medical students, looking across the past decade at the influence of tuition and fees (tuition-fees) alone and the total costs of attending school, the effects of the changing demographics of medical school enrollments and lengthened graduation times, the relationship between the availability of school-funded scholarships and the amount of student loan disbursements, the pattern of student financial aid, and the reliance on borrowing to cover the costs of medical education. In constant dollars, the average indebtedness of students graduating from public schools increased 59.2% between 1985 and 1995, and that for graduates of private schools increased 64.2%. The fraction of graduates bringing debt with them when they entered medical school declined from 42.1% in 1985 to 33.6% in 1995. Premedical debt as a fraction of total debt declined at public schools from 9% in 1985 to 7% in 1995, and at private schools from 7.8% in 1985 to 5.9% in 1995. For public schools, tuition-fees increased 60.1% between 1985 and 1995, and average medical school debt increased 60.9%; for private schools, tuition-fees increased 30.1% over that period, while average medical school debt increased 66.2%. On average, public school graduates accrued debt greater than their four-year tuition-fee payments, while the average debt accrued by private school graduates was less than tuition-fee amounts. In 1995, graduates of public schools had debt accumulations representing 62% of the average total cost of attendance (tuition, fees, books, supplies, equipment, and living expenses), and the indebtedness of private school graduates was 55% of the average total cost, findings suggesting that total costs were the stronger driver of the amounts borrowed. On a national scale, the influences on medical school debt of longer graduation times, the growing number of women students, greater racial-ethnic diversity, and the admission of more older students age were negligible or small. The average parental income, adjusted to constant dollars, actually increased between 1985 and 1995. For public schools, the aggregate amounts of student aid have climbed at a steeper rate than schools' tuition-fee revenues during the past decade. For public schools, tuition-fee revenues rose 66.7% between 1985 and 1995, while the amount of loans to students at public schools increased 92.7%. For private schools, tuition-fee revenues went up 36.5%, and the amount of loans to students rose 57.9% during the same period. Federal Stafford Loans represented the major financing source, increasing from 71.5% of public schools' tuition-fee revenue in 1985 to 92.2% in 1995, and from 23% of private schools' tuition-fee revenue in 1985 to 38% in 1995. Over the decade, scholarship support kept pace with tuition-fee increases at public schools, but lagged behind the increases at private schools. The recent escalation of student debt has coincided with the lifting of the federal loan borrowing limits under the Higher Education Act. In parallel, entering medical students have declared their intentions to rely more heavily on loans as a means of financing. These findings, although based on national data and trends, provide a framework for exploration of the factors affecting educational costs and financing at individual medical schools. The importance of doing so is mounting, as students may be throwing caution to the winds in the more favorable climate for borrowing, ignoring indicators of changing practice opportunities and incomes ahead.


Can autologous platelet-rich plasma gel enhance healing after surgical extraction of mandibular third molars?
This investigation assesses the effect of platelet-rich plasma (PRP) gel on postoperative pain, swelling, and trismus as well as healing and bone regeneration potential on mandibular third molar extraction sockets. A prospective randomized comparative clinical study was undertaken over a 2-year period. Patients requiring surgical extraction of a single impacted third molar and who fell within the inclusion criteria and indicated willingness to return for recall visits were recruited. The predictor variable was application of PRP gel to the socket of the third molar in the test group, whereas the control group had no PRP. The outcome variables were pain, swelling, and maximum mouth opening, which were measured using a 10-point visual analog scale, tape, and millimeter caliper, respectively. Socket healing was assessed radiographically by allocating scores for lamina dura, overall density, and trabecular pattern. Quantitative data were presented as mean. Mann-Whitney test was used to compare means between groups for continuous variables, whereas Fischer exact test was used for categorical variables. Statistical significance was inferred at P < .05. Sixty patients aged 19 to 35 years (mean: 24.7 ± 3.6 years) were divided into both test and control groups of 30 patients each. The mean postoperative pain score (visual analog scale) was lower for the PRP group at all time points and this was statistically significant (P < .05). Although the figures for swelling and interincisal mouth opening were lower in the test group, this difference was not statistically significant. Similarly, the scores for lamina dura, trabecular pattern, and bone density were better among patients in the PRP group. This difference was also not statistically significant. The PRP group recorded reduced pain, swelling, and trismus as well as enhanced and faster bone healing compared with those in the control. Hence the study showed that topical application of PRP gel has a beneficial effect in enhancing socket healing after third molar surgery.


Effects of hindbrain melanin-concentrating hormone and neuropeptide Y administration on licking for water, saccharin, and sucrose solutions.
Melanin-concentrating hormone (MCH) and neuropeptide Y (NPY) are orexigenic peptides found in hypothalamic neurons that project throughout the forebrain and hindbrain. The effects of fourth ventricle (4V) infusions of NPY (5 microg) and MCH (5 microg) on licking for water, 4 mM saccharin, and sucrose (0.1 and 1.0 M) solutions were compared to identify the contributions of each peptide to hindbrain-stimulated feeding. NPY increased mean meal size only for the sucrose solutions, suggesting that caloric feedback or taste quality is pertinent to the orexigenic effect; MCH infusions under identical testing conditions failed to produce increases for any tastant. A second experiment also observed no intake or licking effects after MCH doses up to 15 microg, supporting the conclusion that MCH-induced orexigenic responses require forebrain stimulation. A third experiment compared the 4V NPY results with those obtained after NPY infusions (5 microg) into the third ventricle (3V). In contrast to the effects observed after the 3V NPY injections and previously reported forebrain intracerebroventricular (ICV) NPY infusion studies, 4V NPY failed to increase meal frequency for any taste solution or ingestion rate in the early phases of the sucrose meals. Overall, 4V NPY responses were limited to intrameal behavioral processes, whereas forebrain ICV NPY stimulation elicited both consummatory and appetitive responses. The dissociation between MCH and NPY effects observed for 4V injections is consistent with reports that forebrain ICV injections of MCH and NPY produced nearly dichotomous effects on the pattern of licking microstructure, and, collectively, the results indicate that the two peptides have separate sites of feeding action in the brain.


Role of the hybrid Bcr/Abl kinase in the pathogenesis of chronic myeloid leukemia lacking C-Abl and CXCR4 proteins.
Philadelphia chromosome is a result of chromosomal rearrangement that leads to the appearing of the hybrid gene bcr/abl. A hybrid mRNA transcribes from bcr-promoter and many copies of hybrid molecules of Bcr/Abl protein are formed as a result of bcr/abl gene expression. It is supposed that a hybrid Abl molecule, replacing the normal one, in majority of cases functions abnormally or does not function at all. Also it is possible that Abl moiety of Bcr/Abl protein which is possibly recognized by some hypothetical cell control system interpreted by cell as an overproduction of c-abl. This, probably, leads to blocking the normal C-Abl molecules production from the normal c-abl gene transcribed from the second non-aberrant chromosome 9. Based on C-Abl physiological functions in conjunction with the most important proteins of which functions directly depend on its activity we tried to outline the research directions that might explain disruptions of the processes at chronic myeloleukosis such as cell migration due to CXCL12/CXCR4 axis activation, reparation, apoptosis, control for mitochondria state, and to propose new perspective therapeutic approaches based on all this knowledge.


[The state of cyclic nucleotide system and morphofunctional changes of lung and heart tissues in hypoxia of different genesis].
It was investigated the intercommunication of the functional state of cyclic nucleotides (CN) system and morphofunctional states of lung and heart tissues and influence on these state of lipid peroxidation processes and adenylate cyclase system activity under development in organism of the hypoxic states of different genesis. Obtained dates testify that with the changes of cAMP and cGMP concentrations, and also with their ratio the level of hyperhydratation of air-blood and blood-tissue barriers under the used influence on the organism are closely correlated. Intercommunication of the cyclic nucleotides system functioning and tissues oxygen consumption at the used influences carries sufficiently difficult and ambiguous character. It was shown that exactly at blood loss in lung and heart tissues there were the parallel diminishing of concentrations both cAMP and cGMP. It is accepted to correlate with a favorable histological dynamics. Exactly under these conditions the correlation of CN concentrations is possible to consider balanced and sent to limitation of displays of unfavorable influence of blood loss on investigated tissues ultrastructure. So, there is a tissue specific and depending from the type of influence on the organism character of intercommunication of the functional state of cyclic nucleotides system and morphofunctional states of lung and heart tissues.


Association of hard and soft tissue factors with gingival recession in orthodontically treated patients: A retrospective study.
Orthodontic treatment is thought as a contributory factor in the development of recession. The objective of this study was to determine the factors associated with a gingival recession in patients who underwent orthodontic mechano-therapy. A retrospective chart review of 72 post-orthodontic cases done at the dental clinics of Aga Khan University hospital that were treated from 2009 to 2017. After evaluating dental records patients were recruited based on inclusion and exclusion criteria. Patients were divided into two groups based on the presence or absence of gingival recession on posttreatment photographs. Patients in each group were further assessed on the following factors: (1) Lower incisor inclination (IMPA). (2) Tissue thickness on the facio-lingual dimension. (3) Alveolar bone height. (4) Alveolar bone thickness. The mean age of patients at the start of treatment was 16.56±5.66years. Gingival recession was found in 40.3% of our patients while 59.7% of patients had no recession found after orthodontic treatment. Univariable logistic regression was applied for factors associated with a gingival recession following orthodontic treatment which showed that the odds ratio of gingival recession in thin gingival biotype are 14.4 times more than in thick gingival biotype. Multivariable regression analysis showed that the cases had 10.2 times more recession in thin biotype than those in the thick gingival biotype while adjusting for pre- and posttreatment alveolar heights following orthodontic treatment and with a confidence interval [95% CI=2.69 to 38.40]. It was concluded from this study that 40% of patients developed gingival recession in one or more teeth during orthodontic treatment. Among different factors pre-treatment, gingival biotype of patients and male gender were the factors that were more associated with the development of gingival recession.


Acute exercise on memory function: open vs. closed skilled exercise.
Background: Previous studies suggest that acute exercise may improve memory function. Few studies, however, have investigated the differential effect of the acute exercise movement patterns on memory. Such an effect is plausible, as research demonstrates that open-skilled exercise (e.g.,racquetball) may have a greater effect on memory-related neurotrophins (e.g., brain-derived neurotrophic factors) when compared to closed-skilled exercise (e.g. treadmill exercise). A key distinction between open- and closed-skilled exercise is that open-skilled exercises are those that require an individual to react in a dynamic way to a changing, unpredictable environment. Our aim in this study was to assess wether retrospective and prospective memory are differentially influenced from open- and closed-skilled acute exercise. Methods: A within-subject design was employed. Participants (Mage = 20.6 years; 69% female)completed two visits, in a counterbalanced order. The two experimental conditions included open-skilled acute exercise (racquetball) and closed-skilled acute exercise (treadmill exercise),each lasting 30-minute at 60% of heart rate reserve (HRR). During both experimental conditions,participants completed short- and long-term assessments of retrospective and prospective memory function. Retrospective memory was evaluated across multiple word-list trials (e.g.,Trials 1-6, 20-minute delay, 24-hour delay). Results: No significant effect of exercise was found on prospective memory. For retrospective memory, there was a significant main effect for condition, F(1, 57) = 5.33, P = 0.02, η2 = 0.004,main effect for trial, F(4.12, 234.9) = 227.85, P < 0.001, η2 = 0.46, but no condition by trial interaction, F(4.63, 264.08) = 1.022, P = 0.40, η2 = 0.002. Conclusion: Retrospective memory was greater after closed-skilled exercise (treadmill) when compared to open-skilled exercise (racquetball).


"Model t" cells: a time-tested vehicle for gene therapy.
T lymphocytes first carried foreign genes safely into humans over two decades ago. Since these pioneering studies, scientific techniques to better understand the genomic landscape of cells has directly led to a more sophisticated appreciation of the diversity, functional complexity, and therapeutic potential of T cells. Through the use of mouse models, we now know the function of the many genes that are critical for T cells to recognize foreign, mutated, or self-antigens and the factors responsible for the lineage diversification of T cells that lead to inhibitory or stimulatory immune responses. This knowledge combined with well-established modalities to introduce genes into T cells allows for the design of effector and memory CD8 and CD4 T lymphocytes specific for viral, fungal, bacterial, parasitic, and tumor-antigens and to design regulatory lymphocytes specific for the self-antigens responsible for autoimmune and inflammatory diseases. Here, I review strategies for designing the ideal T cell by introducing genes controlling (1) the secretion of cytokines/chemokines and their receptors, (2) T-cell receptor specificity, (3) chimeric-antigen receptors that enable for the recognition of surface antigens in an MHC-independent fashion, (4) co-stimulatory/inhibitory surface molecules, and (5) disease defining single-gene factors.


Impact of Alternative Splicing on the Human Proteome.
Alternative splicing is a critical determinant of genome complexity and, by implication, is assumed to engender proteomic diversity. This notion has not been experimentally tested in a targeted, quantitative manner. Here, we have developed an integrative approach to ask whether perturbations in mRNA splicing patterns alter the composition of the proteome. We integrate RNA sequencing (RNA-seq) (to comprehensively report intron retention, differential transcript usage, and gene expression) with a data-independent acquisition (DIA) method, SWATH-MS (sequential window acquisition of all theoretical spectra-mass spectrometry), to capture an unbiased, quantitative snapshot of the impact of constitutive and alternative splicing events on the proteome. Whereas intron retention is accompanied by decreased protein abundance, alterations in differential transcript usage and gene expression alter protein abundance proportionate to transcript levels. Our findings illustrate how RNA splicing links isoform expression in the human transcriptome with proteomic diversity and provides a foundation for studying perturbations associated with human diseases.


Photochemical Production and Photolysis of Acrylate in Seawater.
The marine organosulfur cycle has been studied intensively for over 30 years motivated by the hypothesis that dimethylsulfide (DMS) affects Earth's radiation balance and climate. The main source of DMS is from the enzymatic lysis of dimethylsulfoniopropionate (DMSP), the latter of which is a significant component of carbon, sulfur, and energy fluxes in the oceans. Acrylate is also produced during DMSP lysis, but unlike DMS or DMSP, very little is known about the marine acrylate cycle. Herein, a new source of acrylate was identified in seawater as a product formed from the photolysis of dissolved organic matter (DOM). Photochemical production rates varied from 1.6 to 5.0 pM (μmol quanta cm-2)-1, based on photon exposures determined from nitrite actinometry. A positive correlation (r = 0.87) was observed between acrylate photoproduction and the seawater absorption coefficient at 330 nm. Acrylate photoproduction was initiated by UV radiation, with UV-B and UV-A contributing approximately 32 and 68% to the total production, respectively. Acrylate did not photolyze in high-purity water or seawater at concentrations less than 100 nM. These findings improve our understanding of the role that sunlight plays in the marine acrylate cycle, a reactive form of DOM that significantly affects the carbon cycle and ecology of the upper ocean.


Surface photochemistry of CO adsorbed on alumina supported nanoparticulate platinum.
Laser induced desorption of CO adsorbed on platinum nanoparticles on an epitaxial alumina support grown on NiAl(110) is reported for nanosecond laser excitation at λ = 355 nm. The nominal amount of platinum deposited was 0.1 nm, resulting in platinum particles with an average diameter of a few nanometres. The laser fluence was systematically varied between 6.4 and 25.5 mJ cm (- 2) per pulse. Fourier transform infrared reflection absorption spectra have been recorded as a function of CO coverage, the laser fluence and the number of photons impinging on the surface. Laser desorption is observed, in contrast to the case for experiments on Pt(111) for the same laser wavelength. For laser fluences below 12.7 mJ cm (- 2) per pulse, a cross section of (1.1 ± 0.2) × 10 (- 19) cm(2) can be estimated from the measurements. At elevated fluences a second desorption channel occurs with a cross section more than an order of magnitude larger, scaling linearly with the laser fluence. In all cases desorption ends at a critical coverage beyond which no desorption occurs and which depends on the laser fluence. Laser induced particle morphology changes are observed for higher laser fluences which are not apparent for bare particles. A model implying energy pooling within adsorbates at hot spots and even spillover between the metal nanoparticles and the oxidic support is discussed. Implications for the design of photocatalysts with possible use in chemical solar energy conversion are pointed out.


Crystal structure of an orthomyxovirus matrix protein reveals mechanisms for self-polymerization and membrane association.
Many enveloped viruses encode a matrix protein. In the influenza A virus, the matrix protein M1 polymerizes into a rigid protein layer underneath the viral envelope to help enforce the shape and structural integrity of intact viruses. The influenza virus M1 is also known to mediate virus budding as well as the nuclear export of the viral nucleocapsids and their subsequent packaging into nascent viral particles. Despite extensive studies on the influenza A virus M1 (FLUA-M1), only crystal structures of its N-terminal domain are available. Here we report the crystal structure of the full-length M1 from another orthomyxovirus that infects fish, the infectious salmon anemia virus (ISAV). The structure of ISAV-M1 assumes the shape of an elbow, with its N domain closely resembling that of the FLUA-M1. The C domain, which is connected to the N domain through a flexible linker, is made of four α-helices packed as a tight bundle. In the crystal, ISAV-M1 monomers form infinite 2D arrays with a network of interactions involving both the N and C domains. Results from liposome flotation assays indicated that ISAV-M1 binds membrane via electrostatic interactions that are primarily mediated by a positively charged surface loop from the N domain. Cryoelectron tomography reconstruction of intact ISA virions identified a matrix protein layer adjacent to the inner leaflet of the viral membrane. The physical dimensions of the virion-associated matrix layer are consistent with the 2D ISAV-M1 crystal lattice, suggesting that the crystal lattice is a valid model for studying M1-M1, M1-membrane, and M1-RNP interactions in the virion.


Effect of whole-body vibration for 3 months on arterial stiffness in the middle-aged and elderly.
Cardiovascular disease (CVD) is a common problem of middle-aged and older adults. Increased arterial stiffness is a CVD risk factor. Whole-body vibration (WBV) is a simple and convenient exercise for middle-aged and older adults; however, there have been few studies investigating the effect of WBV on arterial stiffness. This study mainly investigated the effect of WBV on arterial stiffness in middle-aged and older adults. A total of 38 (21 women and 17 men) middle-aged and elderly subjects (average age, 61.9 years) were randomly divided into the WBV group and the control group for a 3-month trial. The WBV group received an intervention of 30 Hz and 3.2 g WBV in a natural full standing posture at a sports center. The brachial-ankle pulse wave velocity (baPWV), a marker of systemic arterial stiffness, and blood pressure and heart rate were measured before and after the intervention. After 3 months, there were no significant changes in blood pressure or heart rate in both groups. However, the bilateral baPWV was significantly reduced in the WBV group (decreased by 0.65 m/second [P=0.014]; 0.63 m/second [P=0.041] in either side), but not in the control group. The comparison between the two groups was not statistically significant. This study found that 3 months of WBV had a positive effect on arterial stiffness in middle-aged and older adults and could therefore be regarded as a supplementary exercise. Larger-scale studies are needed to confirm the effects of WBV in the future.


Clinical Efficacy of Nutritional Supplements in Atopic Dermatitis: Systematic Review.
Atopic dermatitis (AD), also known as eczema, is a chronic inflammatory skin condition that presents with symptoms of intense pruritus, dryness, and erythema. Dissatisfaction with first-line therapies for AD, the desire to avoid steroids, and the extreme cost of effective biologics have created a demand for alternative treatment options such as oral vitamins and nutritional supplements. The purpose of this review was to assess the effectiveness of oral nutritional supplements, pre- and probiotics, and vitamin deficiencies and supplements on AD symptomology and clinical course. We searched Scopus, PubMed, and MEDLINE (Ovid interface) for English-language articles published between 1993 and 2023. The final search was conducted on June 22, 2023. The search terms comprised the following: "(Atopic Dermatitis or Atopic Eczema) AND (supplement OR vitamin OR mineral OR micronutrients OR Fish Oil OR Omega Fatty Acid OR Probiotics OR Prebiotics OR apple cider vinegar OR collagen OR herbal OR fiber)." A total of 18 studies-3 (17%) evaluating vitamins, 4 (22%) evaluating herbal medicine compounds, 2 (11%) evaluating single-ingredient nutritional supplements, and 9 (50%) evaluating pre- and probiotics-involving 881 patients were included in this review. Overall, there is weak evidence to support any one nutritional supplement intervention for the alleviation of AD symptoms. Multiple trials (4/18, 22%) showed promise for supplements such as Zemaphyte, kefir, and freeze-dried whey with Cuscuta campestris Yuncker extract. The most evidence was found on the effectiveness of probiotics on the clinical course of AD. Lactiplantibacillus plantarum, Ligilactobacillus salivarius, and Lactobacillus acidophilus specifically showed evidence of efficacy and safety across multiple studies (6/18, 33%). However, larger, more extensive randomized controlled trials are needed to determine the true effectiveness of these supplements on the broader population. PROSPERO CRD42023470596; https://tinyurl.com/4a9477u7.


Disulfiram metabolism as a requirement for the inhibition of rat liver mitochondrial low Km aldehyde dehydrogenase.
In humans and animals, disulfiram produces a disulfiram-ethanol reaction after an ethanol challenge, the basis of which is the inhibition of liver aldehyde dehydrogenase (ALDH). Disulfiram and the metabolites diethyldithiocarbamate (DDTC), diethyldithiocarbamate-methyl ester (DDTC-Me), and S-methyl-N,N-diethylthiolcarbamate (DETC-Me) were studied in order to determine the role of bioactivation in disulfiram's action as an inhibitor of rat liver mitochondrial low Km ALDH (RLM low Km ALDH). In in vitro studies, disulfiram and DDTC (0.01 to 2.0 mM) both inhibited RLM low Km ALDH in a concentration-dependent manner. The addition of rat liver microsomes to the mitochondrial incubation did not further increase disulfiram-induced RLM low Km ALDH inhibition. However, DDTC-induced RLM low Km ALDH inhibition was increased further, but only at DDTC concentrations less than 0.05 mM. DDTC-Me and DETC-Me (2.0 mM) similarly exhibited an increased RLM low Km ALDH inhibition after the addition of liver microsomes. In in vivo studies, disulfiram (75 mg/kg), DDTC (114 mg/kg), DDTC-Me (41.2 mg/kg) or DETC-Me (18.6 mg/kg) administered i.p. to female rats inhibited RLM low Km ALDH. Inhibition of drug metabolism by pretreatment of rats with the cytochrome P450 inhibitor N-octylimidazole (NOI) (20 mg/kg, i.p.) prior to either disulfiram, DDTC, DDTC-Me or DETC-Me administration blocked the inhibition of RLM low Km ALDH. The in vitro and in vivo data support the conclusion that bioactivation of disulfiram to a reactive chemical species is required for RLM low Km ALDH inhibition and a disulfiram-ethanol reaction.


Study of the effect of Anisakis simplex larval products on the early and late components in the classical complement pathway.
In previous studies, we have reported that the larval products (crude extract [CE] and excretory-secretory [ES]) of Anisakis simplex showed a dose-dependent inhibition of the lysis mediated by classical (CP) and alternative pathways (AP) of the human complement system, with the major inhibition on the CP rather than on AP. This inhibition of hemolysis is due to the consumption of complement factors because the assays performed shortening the preincubation period result in a significant decrease of the inhibitory effect on the lysis of the larval products compared with the standard time. Likewise, we found that the larval products reduce the inhibitory percentages in the CP using C3-deficient sera, but not in the AP, which could indicate that other complement components are implicated in the inhibitory effect in the CP. Hence, we have studied the activity of the larval products of A. simplex on individual components in the CP, using different complement-deficient sera. The investigated complement molecules were C1q, C2, C4, C5, C6, C7, C8, and C9. The larval products showed activity at the C2 level but failed to have a significant effect on the other components. Therefore, CE and ES products from A. simplex interact with C3 and C2 complement proteins, which are early components of the complement system, but not with the late complement components.


Glycogen Levels in Undiluted Genital Fluid and Their Relationship to Vaginal pH, Estrogen, and Progesterone.
Colonization of the female lower genital tract with Lactobacillus provides protection against STIs and adverse pregnancy outcomes. Growth of genital Lactobacillus is postulated to depend on epithelial cell-produced glycogen. However, the amount of cell-free glycogen in genital fluid available for utilization by Lactobacillus is not known. Eighty-five genital fluid samples from 7 pre-menopausal women taken over 4-6 weeks were obtained using the Instead SoftCup® (EvoFem, Inc., San Diego, CA, USA) by consented donors. Cell-free glycogen and glucose in genital fluids and estrogen and progesterone in blood were quantified. Glycogen ranged from 0.1-32 μg/μl. There were significant differences between women in glycogen over the observation period. There was a strong negative correlation between glycogen and vaginal pH (r = -0.542, p<0.0001). In multivariable analysis, free glycogen levels were significantly negatively associated with both vaginal pH and progesterone (p < 0.001 and p = 0.004, respectively). Estrogen, glucose, age, sexual intercourse 24 hours prior to visit, and days after the initial visit were not significantly associated with free glycogen levels. Cell-free glycogen concentrations can be very high, up to 3% of genital fluid, and are strongly associated with acidic vaginal pH. However, the fluctuations in glycogen levels in individuals and differences between individuals do not appear to be associated with estrogen.


Relaxin contributes to the regulation of arterial pressure in adult female mice.
Relaxin is increasingly being recognized as a potent vasodilatory and antifibrotic hormone. Given that relaxin is present in the circulation during the luteal phase of the menstrual cycle and during pregnancy, when arterial pressure is lowest in women, relaxin may contribute to the relative cardiovascular protection observed in premenopausal women as compared with age-matched men and postmenopausal women. In the present study, we investigated the contribution of relaxin to the normal regulation of arterial pressure in adult female and male mice and during pregnancy. Mean arterial pressure (MAP) was measured via radiotelemetry in 14-week-old male and female wild-type (WT; C67BL/6xSv129) and relaxin knockout (KO) mice. Thereafter, female mice were time-mated with a (non-telemetered) male of the same genotype and MAP was measured throughout gestation. Basal MAP was ∼10 mmHg lower in WT females than males (P<0.05). Relaxin deficiency increased basal MAP in females (P<0.05 vs WT female), but not males. As expected, MAP decreased during gestation in WT mice. Conversely, in relaxin KO mice, arterial pressure increased during mid and late gestation (P<0.05 as compared with WT). Moreover, relaxin deficiency impaired gestational weight gain and reduced litter size. This is the first study to (i) demonstrate that relaxin contributes to the sexual dimorphism of arterial pressure in mice and (ii) document the changes in the arterial pressure profile of pregnant relaxin KO mice. Understanding the mechanisms that underlie the regulation of arterial pressure in premenopausal females may uncover new strategies to treat hypertension in women (non-pregnant and pregnant) and men.