Application of quantitative analysis of multi-component system approach for determination of ginsenosides in different mass-spectrometric conditions.
The lack of standard substances is a bottleneck for quality control in traditional and alternative medicine. Development of the HPLC-UV approaches combined with single standard for quantitative analysis of multi-component system (QAMS) allowed determination of several plant biomarkers by implementation of the relative response factors (RRFs). Robustness and ruggedness of such methods are commonly demonstrated by performing the analysis in changing analytical conditions on the different HPLC equipment and columns. The nature of MS detection is much more complicated and dependent on the instrumentation. Therefore, this study was conducted to justify the use of RRFs for HPLC-MS determination of bioactive compounds from plants. Protopanaxatriol (PPT), protopanaxadiol (PPD) and ocotillol (OT) ginseng saponins (ginsenosides) were successfully separated on a reversed-phase PFP-column with high group selectivity. Fragmentation patterns for these groups of compounds were established on different HPLC-ESI-MS systems and at varied declustering potentials (DPs). The use of sapogenin fragmentation ions in positive detection mode along with group reference standards was shown to be an optimal way to perform quantification. The performance of the developed group targeted HPLC-MS-QAMS approach was tested in the course of measurements conducted on the different instrumentation. The differences between QAMS and external standard method (ESM) quantification results were below 15% for all determined saponins.


Lymphomatoid granulomatosis apparently confined to one temporal lobe. Case report.
Lymphomatoid granulomatosis is of uncertain etiology and poses problems with diagnosis and treatment. A case with involvement of the right temporal lobe, but associated with cystoid macular edema of the retina, is described. The unusual mode of presentation, the radiographic, operative, and pathological findings, the response to surgery and radiotherapy, and the possible etiology are discussed.


Biochemical characterization of a p43,12 complex: comparison with human and murine class I molecules.
A monoclonal antibody designated as C21 reacting with a p43,12 complex was developed against human thymocytes. It stained predominantly the early hematopoietic cells of the lymphoid lineage and also thymocytes, peripheral B-cells and activated T- and B-cells similarly to OKT10. The heavy chain of this antigen was a glycoprotein of Mr 43,000 (p43). Sequential immunoprecipitation with C21 and OKT10 antibodies indicated that they both reacted with an identical heavy-chain molecule. This observation was further documented by two-dimensional analysis. Monoclonal antibody C21 was used to probe a p43,12 complex further. Structural polymorphism of the p43 heavy chain isolated from T- and B-cells of different individuals was not detected by chymotryptic peptide mapping, although molecules from these cell types possessed a different charge on two-dimensional gels. An unusual observation was made regarding this complex on MOLT4 cells. The light chain co-precipitated from these cells was 12,000 daltons and had a pI distinct from that of beta 2-microglobulin but similar to the pI of the beta t molecule. Comparison between chymotryptic peptide maps of the p43 heavy chain and those of the human and murine class I molecules such as HLA, T6, H-2K, Qa-2 and TL revealed no apparent homology. We have shown, however, that the peptide backbone of p43, as studied by both tunicamycin treatment of cells and endoglycosidase F digestion of immunoprecipitates, was identical in size to that of murine Qa-1. These results suggest that the p43 antigen may be homologous to murine Qa-1 or another class I antigen encoded in the murine TL:Qa region.


New insights in the in vitro release of phenolic antioxidants: The case study of the release behavior of tyrosol from tyrosol-loaded ethylcellulose microparticles during the in vitro gastrointestinal digestion.
In this study, tyrosol - a phenolic antioxidant that present in olive oil and olive mill wastes - was embedded in ethylcellulose microparticles by double emulsion solvent evaporation technique. The effect of loading content (5 % w/w and 10 % w/w) on the release behavior and bioaccessibility of tyrosol was evaluated. The polymer endowed efficient protection to tyrosol during the in vitro gastrointestinal digestion of loaded microparticles as the maximum release of tyrosol was observed during the simulated intestinal digestion, and the releases were kept outstanding low during the simulated salivary and gastric digestions. The bioaccessibility of tyrosol was improved when encapsulated. The best-fitting models of the release profiles of tyrosol were the first, and the zero-order models for formulations considering a loading of 5% w/w and 10 % w/w, respectively. The results of this study bring new perspectives for the design of loaded microparticles that will be further submitted to gastrointestinal digestion.


A biomechanical comparison of lifting techniques between subjects with and without chronic low back pain during freestyle lifting and lowering tasks.
To evaluate if chronic low back pain patients perform manual material handling tasks differently from control subjects. Comparative study using a repeated measures design. No study evaluated the lifting technique of back pain patients relative to control subjects during free style lifting and lowering tasks. Previous findings suggest that lowering would be more hazardous than lifting to the low back. It would be interesting to evaluate if chronic low back pain patients behave differently than controls when lifting and lowering. Thirty-three male subjects (18 controls, 15 suffering from non-specific chronic low back pain) participated. A 12-kg box was lifted (freestyle) from the floor to the hips (1) in front (symmetric task) or (2) to a shelf located at 90 degree on the right (asymmetric task) and was lowered back to the floor. A 3D biomechanical analysis involving the assessment of L5/S1 loading, posture of segments, inertial parameters, and EMG was performed. There was no difference between the groups for postural (trunk and lower limb angles), inertial (trunk velocity and acceleration), and L5/S1 loading (moments and compression) variables. The patients showed abnormally low left lumbar erector spinae (symmetric task, lowering) or high left thoracic erector spinae (all tasks) EMG activation. Significant Group x Action (lifting vs. lowering) interactions were also observed for some inertial and L5/S1 loading variables suggesting that the biomechanical differences detected between lifting and lowering may have a differential influence on the technique used by back pain patients and control subjects. The gross lifting technique of back pain patients was unaltered relative to controls but the activation of paraspinal muscles differed, suggesting that a more detailed biomechanical analysis, such as the use of EMG driven models, might be required to reveal lumbar impairments during lifting. To evaluate if chronic low back pain patients use naturally different lifting techniques to prevent pain exacerbation and damaged lumbar tissue overloading.


Effects of a high-carbohydrate diet on blood glucose, insulin and triglyceride levels in normal and obese subjects and in obese subjects with impaired glucose tolerance.
1. The present study was performed in order to assess the influence of a high-carbohydrate diet on carbohydrate and lipid metabolism in humans. 2. Short-term (3 weeks) and long-term (6 weeks) effects of a high-carbohydrate diet (HCD, 85% carbohydrate) were compared with the effects of 2 weeks on a diet of normal carbohydrate content (ND, 45% carbohydrate). The study was conducted on 4 normal and 11 obese subjects (with normal or impaired glucose tolerance) on a metabolic ward. Fasting blood glucose, insulin and triglyceride levels were measured twice a week. Tolerance to carbohydrates was evaluated by measuring blood glucose and insulin levels after oral and intravenous glucose loads and liquid meals at intervals throughout the 8-week period. 3. Long-term HCD improved the tolerance to oral glucose, i.e., it decreased serum glucose and insulin responses to an oral glucose load. 4. HCD had no effects on fasting levels of glucose or insulin or on the tolerance to an intravenous glucose load. 5. A high-carbohydrate liquid meal induced greater post-prandial glucose and insulin levels than a normal liquid meal. 6. In a second group of 6 normal and 6 obese subjects, efficacy of the liquid meal tests was evaluated. A high-carbohydrate liquid meal induced greater glucose and insulin responses than a normal liquid meal during both dietary periods. 7. Fasting triglyceride levels increased and remained high throughout the HCD period.


Comparison of Clinical Subtypes of Breast Cancer within the Claudin-Low Molecular Cluster Reveals Distinct Phenotypes.
Molecular subtyping of breast cancer has provided a new perspective on the pathogenesis of the disease and a foundation for building a clinical classification for this heterogeneous disease. The initial classification categorizing breast cancers into five groups, luminal A, luminal B, ERBB2-overexpressing, basal-like and normal-like, was later supplemented by an additional group, claudin-low tumors. However, the claudin-low group has been more difficult to align with clinically used immunohistochemical categories. The identity of this group among clinical cases remains ill defined. The METABRIC cohort comprising more than 1700 breast cancers and providing information for classifying them in both clinical groups and the genomic PAM50/claudin-low groups was analyzed to derive relationships and clarify potential pathogenic ramifications. Comparisons of the claudin-low cases bearing different clinical group classifications and of the respective cases with the same clinical non-claudin-low classifications were performed. ER-negative/HER2-negative breast cancers are predominantly (88.4%) basal-like and claudin low. Conversely, most basal-like cancers (83.6%) are ER negative/HER2 negative. However, claudin-low breast cancers are only in 68.4% of cases ER negative/HER2 negative and the other clinical phenotypes, mostly ER positive/HER2 negative/low proliferation, are also represented in more than 30% of claudin-low cancers. These claudin-low non-ER-negative/HER2-negative breast cancers differ from claudin-low ER-negative/HER2-negative cases in grade, prevalence of integrative clusters, and prevalence of common mutations and common amplifications. Differences also exist between the two groups classified clinically as ER negative/HER2 negative, that are genomically basal-like or claudin-low, including in menopause status, grade, histology, prevalence of high tumor mutation burden, distribution of integrative clusters, prevalence of TP53 mutations and of amplifications in the MYC and MCL1 loci. Furthermore, distinct characteristics are observed between the luminal A and claudin-low groups within the clinical ER-positive/HER2-negative/low proliferation group. Within genomically claudin-low breast cancers, the ER-negative/HER2-negative group is distinct from the group with either ER or HER2 positivity. Conversely, within clinical phenotypes, claudin-low and non-claudin-low breast cancers differ in clinical characteristics and molecular attributes.


Role of neuropeptide Y and proopiomelanocortin in fluoxetine-induced anorexia.
Fluoxetine is an anorexic agent known to reduce food intake and weight gain. However, the molecular mechanism by which fluoxetine induces anorexia has not been well-established. We examined mRNA expression levels of neuropeptide Y (NPY) and proopiomelanocortin (POMC) in the brain regions of rats using RT-PCR and in situ hybridization techniques after 2 weeks of administering fluoxetine daily. Fluoxetine persistently suppressed food intake and weight gain during the experimental period. The pair-fed group confirmed that the reduction in body weight in the fluoxetine treated rats resulted primarily from decreased food intake. RT-PCR analyses showed that mRNA expression levels of both NPY and POMC were markedly reduced by fluoxetine treatment in all parts of the brain examined, including the hypothalamus. POMC mRNA in situ signals were significantly decreased, NPY levels tended to increase in the arcuate nucleus (ARC) of fluoxetine treated rats (compared to the vehicle controls). In the pair-fed group, NPY mRNA levels did not change, but the POMC levels decreased (compared with the vehicle controls). These results reveal that the chronic administration of fluoxetine decreases expression levels in both NPY and POMC in the brain, and suggests that fluoxetine-induced anorexia may not be mediated by changes in the ARC expression of either NPY or POMC. It is possible that a fluoxetine raised level of 5-HT play an inhibitory role in the orectic action caused by a reduced expression of ARC POMC (alpha-MSH).


Endovascular management of renal ischemia in a patient with acute aortic dissection and renovascular hypertension.
We report the endovascular management of a patient with a type B aortic dissection complicated by renal ischemia and resultant severe hypertension. A 69-year-old male presented with acute type B aortic dissection with proximal extension complicated by severe renovascular hypertension secondary to left renal ischemia. Endovascular management consisted of imaging with intravascular ultrasound and left renal artery stenting with balloon-expandable stents. His hypertension subsequently resolved and he was discharged on his baseline two-drug regimen. Management of the ischemic complications of type B aortic dissections may be primarily approached using endovascular methods in stable patients, with open surgery reserved for those patients refractory to these methods. Patients with evidence of decreased renal perfusion represent a select group with an increased risk of associated morbidity and mortality and should therefore be aggressively managed. Accurate information and assessment of anatomy can be obtained with intravascular ultrasound and is therefore an important adjunct to the armamentarium of endovascular specialists managing complications of aortic dissection.


Influence of level of education on disability free life expectancy by sex: the ILSA study.
To assess the effect of education on Disability Free Life Expectancy among older Italians, using a hierarchical model as indicator of disability, with estimates based on the multistate life table method and IMaCh software. Data were obtained from the Italian Longitudinal Study on Aging which considered a random sample of 5632 individuals. Total life expectancy ranged from 16.5 years for men aged 65 years to 6 years for men aged 80. The age range for women was 19.6 and 8.4 years, respectively. For both sexes, increasing age was associated with a lower probability of recovery from a mild state of disability, with a greater probability of worsening for all individuals presenting an independent state at baseline, and with a greater probability of dying except for women from a mild state of disability. A medium/high educational level was associated with a greater probability of recovery only in men with a mild state of disability at baseline, and with a lower probability of worsening in both sexes, except for men with a mild state of disability at baseline. The positive effects of high education are well established in most research work and, being a modifiable factor, strategies focused on increasing level of education and, hence strengthening access to information and use of health services would produce significant benefits.


Effects of artificially induced complete mixing on dissolved organic matter in a stratified source water reservoir.
Naturally complete mixing promotes the spontaneous redistribution of dissolved oxygen (DO), representing an ideal state for maintaining good water quality, and conducive to the biomineralization of organic matter. Water lifting aerators (WLAs) can extend the periods of complete mixing and increase the initial mixing temperature. To evaluate the influence of artificial-induced continuously mixing on dissolved organic matter (DOM) removal performance, the variations of DOM concentrations, optical characteristic, environmental factors were studied after approaching the total mixing status via WLAs operation. During this process, the dissolved organic carbon reduced by 39.18%, whereas the permanganate index decreased by 20.47%. The optical properties indicate that the DOM became more endogenous and its molecular weight decreased. Based on the results of the Biolog EcoPlates, the microorganisms were maintained at a relatively high metabolic activity in the early stage of induced mixing when the mixing temperature was relatively high, whereas DOM declined at a high rate. With the continuous decrease in the water temperature, both the metabolic capacity and the diversity of aerobic microorganisms significantly decreased, and the rate of organic matter mineralization slowed down. The results of this study demonstrate that the artificial induced mixing largely enhanced the removal DOM performance by providing a long period of aerobic conditions and higher initial temperature.


Drug Discovery Platform Targeting M. tuberculosis with Human Embryonic Stem Cell-Derived Macrophages.
A major limitation in anti-tuberculosis drug screening is the lack of reliable and scalable models for homogeneous human primary macrophage cells of non-cancer origin. Here we report a modified protocol for generating homogeneous populations of macrophage-like cells from human embryonic stem cells. The induced macrophages, referred to as iMACs, presented similar transcriptomic profiles and characteristic immunological features of classical macrophages and were permissive to viral and bacterial infection, in particular Mycobacterium tuberculosis (Mtb). More importantly, iMAC production was amenable to scale up. To evaluate iMAC efficiency in high-throughput anti-tuberculosis drug screening, we performed a phenotypic screening against intracellular Mtb, involving a library of 3,716 compounds that included FDA-approved drugs and other bioactive compounds. Our primary screen identified 120 hits, which were validated in a secondary screen by dose-intracellular and -extracellular Mtb assays. Our confirmatory studies identified a novel anti-Mtb compound, 10-DEBC, also showing activity against drug-resistant strains.


Nonmyeloablative stem cell transplantation for myelodysplastic syndrome or acute myeloid leukemia in patients 60 years or older.
We analyzed the outcomes of 24 consecutive patients aged >or=60 years with poor-prognosis myelodysplastic syndrome or acute myeloid leukemia undergoing transplantation with nonmyeloablative conditioning using fludarabine (125 mg/m2) and low-dose total body irradiation (2 Gy) followed by allogeneic peripheral blood stem cell grafts from HLA-identical sibling donors. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and mycophenolate mofetil. The median age of the patients was 64 years (range, 60-71 years). In addition to age, 88% of patients had 1 or more adverse biological features of the disease. With a median follow-up of 21 months, 12 patients are alive, 11 of whom are disease free. The probabilities of 2-year overall and progression-free survival were 52% and 44%, respectively. The cumulative probabilities of relapse and of acute and chronic GVHD were 27%, 45%, and 74%, respectively. Nonrelapse mortality at 100 days and 2 years was 8% and 25%, respectively. Of the 15 patients with extensive chronic GVHD, 1 patient relapsed. These data suggest that nonmyeloablative stem cell transplantation is a feasible treatment option in patients aged >or=60 years with poor-prognosis myelodysplastic syndrome or acute myeloid leukemia. The reasonable disease control with nonmyeloablative transplantation in this high-risk group of patients merits further investigation.


Alternative treatment with Johrei: A controlled randomized study evaluating seed physiological potential.
Johrei, a noncontact healing therapy that purportedly channels "universal energy", is an easily taught technique with numerous positive reports of healing in human trials. However, studies on humans have been limited by small sample sizes, the placebo effect and baseline differences between groups. Overcoming some of these limitations, this study evaluated the effect of Johrei on the physiological potential of lettuce seeds. Lettuce seeds were subjected to thermal stress and then treated with Johrei before and after two years of storage. The seedling emergence percentage, emergence speed index, classification score, percentage of viable seedlings and root and shoot dry mass of the treated seeds were determined. Stress-treated seeds treated with Johrei had a greater seedling emergence percentage than those not treated with Johrei (p<0.0001). Johrei also resulted in a greater emergence speed index (p<0.0001), a higher percentage of viable seedlings with higher classification score (p<0.0001) and greater root and shoot dry mass regardless of the storage duration (p<0.0001). Johrei effectively preserved lettuce seed health, and the efficacy of Johrei can be assessed by evaluating its effects on the physiological potential of stress-treated seeds. Using live plants allows the influence of Johrei to be evaluated without interference from the placebo effect. Future studies should evaluate the influence of Johrei in primary aging processes in plants, such as cellular respiration by mitochondrial analysis, to gain insight into Johrei's mechanisms of action and enable inferences regarding similar cellular-level processes that occur in humans.


Validation of a 21-locus autosomal SNP multiplex for forensic identification purposes.
A single nucleotide polymorphism (SNP) multiplex has been developed to analyse highly degraded and low copy number (LCN) DNA template, i.e. <100 pg, for scenarios including mass disaster identification. The multiplex consists of 20 autosomal non-coding loci plus Amelogenin for sex determination, amplified in a single tube PCR reaction and visualised on the Applied Biosystems 3100 capillary electrophoresis (CE) system. Allele-specific primers tailed with shared universal tag sequences were designed to speed multiplex design and balance the amplification efficiencies of all loci through the use of a single reverse and two differentially labelled allele denoting forward universal primers. As the multiplex is intended for use with samples too degraded for conventional profiling, a computer program was specifically developed to aid interpretation. Critical factors taken into account by the software include empirically determined extremes of heterozygous imbalance (Hb) and the drop-out threshold (Ht) defined as the maximum peak height of a surviving heterozygous allele, where its partner may have dropped out. The discrimination power of the system is estimated at 1 in 4.5 million, using a White Caucasian population database. Comparisons using artificially degraded samples profiled with both the SNP multiplex and AMPFISTR SGM plus (Applied Biosystems) demonstrated a greater likelihood of obtaining a profile using SNPs for certain sample types. Saliva stains degraded for 147 days generated an 81% complete SNP profile whilst short tandem repeats (STRs) were only 18% complete; similarly blood degraded for 243 days produced full SNP profiles but only 9% with STRs. Reproducibility studies showed concordance between SNP profiles for different sample types, such as blood, saliva, semen and hairs, for the same individual, both within and between different DNA extracts.


Ligand-activated interaction of PPARδ with c-Myc governs the tumorigenicity of breast cancer.
Peroxisome proliferator-activated receptor (PPAR) δ is a promising therapeutic target in metabolic and inflammatory disorders. However, its role in oncogenesis is controversial, and its therapeutic potential remains to be determined. In our study, we show that ligand-activated PPARδ forms a complex with the proto-oncogene product c-Myc. The interaction of PPARδ with c-Myc affected the transcriptional activity of c-Myc and the expression of its target genes. The PPARδ-dependent regulation of c-Myc activity was associated with decreased tumorigenicity in breast cancer cells. Administration of the PPARδ ligand GW501516 inhibited tumor growth in xenograft model mice bearing MDA-MB-231 cells stably expressing wild-type PPARδ, but not those expressing dominant-negative PPARδ, by interfering with c-Myc function through protein-protein interaction. Our results indicating that PPARδ forms an antitumorigenic complex with c-Myc in the presence of ligand suggest a potential role of PPARδ in breast cancer development.


Phosphate and pepsin adsorptions by a new boehmite compound and aluminum hydroxide.
A new microcrystalline compound of aluminum oxide hydroxide (tentatively named PT-A) was synthesized in the hope of providing a better phosphate adsorbent for future clinical use than the currently marketed aluminum hydroxide gels (ALG). An X-ray diffraction study demonstrated a boehmite structure in PT-A but an amorphous structure in ALG. PT-A was more stable in pH change than ALG; in elution tests in artificial gastric and intestinal solutions, aluminum ion eluted from PT-A was maximally 10% of the amount from ALG at pH 1.2; and was undetectable at pH 6.8, at which point ALG still showed some aluminum elution. Phosphate-adsorbing efficacy of PT-A and ALG in vitro was about the same at pH 1.2; however, it was four times greater in PT-A than in ALG at pH 6.8, indicating that PT-A will be effective in the intestine. PT-A also adsorbed pepsin but the amount was at most the same or much less than that adsorbed by ALG, which depended on pH in solution.


Sense organs on the antennal flagellum of a stonefly (Plecoptera, insecta).
Tactile hairs, small chemoreceptor pegs, thick-walled chemoreceptors, thin-walled chemoreceptors of several types, coeloconic sense organs and campaniform sense organs are present on the flagellum of a stonefly, Allocapnia recta (Claassen).


Diabetic ketoacidosis and insulin resistance with subcutaneous terbutaline infusion: a case report.
Diabetic ketoacidosis may occur in women treated with intravenous beta-sympathomimetic agents for tocolysis. We describe diabetic ketoacidosis and transient severe insulin resistance in a woman with diabetes who was treated with subcutaneous terbutaline infusion. Subcutaneous terbutaline infusion may precipitate transient insulin resistance and diabetic ketoacidosis in women with diabetes.


Nitrogen-Doped Cobalt Pyrite Yolk-Shell Hollow Spheres for Long-Life Rechargeable Zn-Air Batteries.
Limited by the sluggish four-electron transfer process, designing high-performance nonprecious electrocatalysts for the oxygen evolution reaction (OER) and oxygen reduction reaction (ORR) is urgently desired for efficient rechargeable Zn-air batteries (ZABs). Herein, the successful synthesis of porous nitrogen-doped cobalt pyrite yolk-shell nanospheres (N-CoS2 YSSs) is reported. Benefiting from the abundant porosity of the porous yolk-shell structure and unique electronic properties by nitrogen doping, the as-prepared N-CoS2 YSSs possess more exposed active surface, thus giving rise to superior activity for reversible oxygen electrocatalysis and outstanding cycling stability (more than 165 h at 10 mA cm-2) in ZABs, exceeding the commercial Pt/C and RuO2 hybrid catalysts. Moreover, the assembled ZABs, delivering a specific capacity of 640 mAh gZn -1, can be used for practical devices. This work provides a novel tactic to engineer sulfides as high efficiency and promising bifunctional oxygen electrocatalysts for advanced metal-air batteries.


Angiotensin II-induced venoconstriction involves both AT1 and AT2 receptors and is counterbalanced by nitric oxide.
The venoconstrictor effect of Angiotensin II (Ang II) was investigated in the rat mesenteric venules and portal vein. Mesenteric venules were perfused at a constant rate and reactivity to Ang II (0.1 nmol) was evaluated as changes in the perfusion pressure. Rings of portal vein were mounted in organ baths and curves to Ang II (0.1-100 nmol/L) were generated. In venules, Ang II-contraction (10.6+/-1.1 mmHg) was abolished by losartan (0.9+/-0.3 mmHg*), reduced by PD 123,319 (5.8+/-0.9 mmHg*), increased by L-NAME (16.5+/-1.8 mmHg*) and not altered by indomethacin. In portal veins, curves to Ang II (-logEC50: 8.9+/-0.1 mol/L) were shifted to the right by losartan (-log EC50: 7.5+/-0.1 mol/L*) and by PD 123,319 (-logEC50: 8.0+/-0.1 mol/L*). L-NAME increased the maximal response to Ang II (Emax: 0.91+/-0.1g versus 1.62+/-0.3g*) and indomethacin had no effect. In conclusion, Ang II induces venoconstriction by activating AT1 and AT2 receptors. Data obtained with L-NAME provide evidence that the basal nitric oxide release from the endothelium of the venous system can modulate the Ang II-induced venoconstriction.


The "Economic Health" of U.S. Health Care and Role of Middlemen.
This article goes through the major components of the health care return-on-investment equation, from spending to outcomes, and attempts to identify major causes for its underperformance compared with other types of enterprise. It also explores the role of "middlemen" in prescription drug pricing (broadly defined as any market participant other than the drug manufacturer and the provider/patient, including-but not limited to-insurance companies, pharmacy benefit managers [PBMs], and health plans) and teases out the mechanisms by which PBMs, in particular, contribute to overall health care costs and the types of risks and returns they endure. Like any economic system, the health care system is a net zero-sum construct, whereby costs and benefits are traded off or exchanged between components of the value chain involuntarily (e.g., by regulatory or legal mandate) or voluntarily (e.g., by economic incentive). Ultimately, the question for policymakers as it relates to health care reform is to determine what combination of such exchanges leads to the best overall outcomes. This question of optimization, however, is undoubtedly challenging and complex, and can bring to bear economic, social, political, and moral dimensions. In light of these considerations, the article concludes by touching upon some perspectives for the future and ideas for reform, including payer reform, delivery disintermediation by technology, and consumer-driven health care.


Fluorescence demonstration of a cathepsin H-like protease in cardiac, skeletal and vascular smooth muscles.
A cathepsin H-like enzyme was localized by histochemical techniques in cardiac muscle, extensor digitorum longus and soleus skeletal muscles, and vascular smooth muscle. Using the specific exopeptidase activity of this enzyme against the substrate arg-4-methoxy-beta-naphthylamide, valid histochemical assay conditions were developed. More fluorescent granules were observed in cardiac muscle than in the soleus and about equal amounts in vascular smooth muscle and the extensor digitorum longus. The reaction rate was enhanced by chloride ions and inhibited by 1 mM p-chloromercuribenzoate. The maximal activity was observed between pH 5.5 and 6.0 Chemical fixation with periodate-lysine-paraformaldehyde preserved a small amount of enzymatic activity.


The effect of NaCl reduction in the microbiological quality of cracked green table olives of the Maçanilha Algarvia cultivar.
The present work aimed at studying the effect of the partial replacement of NaCl with KCl and CaCl2 of the fermenting brines on the microbiological quality of natural cracked green Maçanilha Algarvia table olives. Olives were fermented in different salt combinations (Brine 1-8% NaCl, Brine 2-4% NaCl 4% KCl, Brine 3-4% NaCl 4% CaCl2, Brine 4-4% KCl 4% CaCl2, and Brine 5-2.7% NaCl 2.7% KCl 2.7% CaCl2) and the abundance of yeasts and enterobacteria was determined. At the end of fermentation, the main microbial safety parameters were evaluated. Samples were analyzed according to standard methodologies and using Chromocult Agar (coliforms and Escherichia coli). The yeasts collected were grouped by restriction analysis of the ITS-5.8S rRNA gene and identified by partial sequencing of the 26S rRNA. Throughout the study, a decrease of the enterobacteria population was observed in all the fermentations, which was greater and faster in brines containing potassium and calcium. The main yeasts identified were Pichia membranaefaciens, Candida boidinii, Zygosaccharomyces mrakii, Priceomyces carsonii, Saccharomyces cerevisiae, Wickerhamomyces anomalus and the yeast-like fungus Galactomyces geotrichum. The highest yeast diversity was found in olives produced in Brines 1, 2 and 3 and the lowest in Brines 4 and 5, where only the species P. membranaefaciens, C. boidinii and G. geotrichum were identified. No Pseudomonas, E. coli, Salmonella, Staphylococcus aureus and Listeria monocytogenes were found in the table olives produced.


Exploiting inhibitor of apoptosis proteins as therapeutic targets in hematological malignancies.
Resistance to apoptosis is one of the hallmarks of human cancers and contributes to the insensitivity of many cancers to commonly used treatment approaches. Inhibitor of apoptosis (IAP) proteins, a family of anti-apoptotic proteins, have an important role in evasion of apoptosis, as they can both block apoptosis-signaling pathways and promote survival. High expression of IAP proteins is observed in multiple cancers, including hematological malignancies, and has been associated with unfavorable prognosis and poor patients' outcome. Therefore, IAP proteins are currently considered as promising molecular targets for therapy. Indeed, drug-discovery approaches over the last decade aiming at neutralizing IAP proteins have resulted in the generation of small-molecule inhibitors or antisense oligonucleotides that demonstrated in vitro and in vivo antitumor activities in preclinical studies. As some of these strategies have already entered the stage of clinical evaluation, for example, in leukemia, an update on this promising molecular-targeted strategy to interfere with apoptotic pathways is of broad interest.


Erratum: Inhibition of Proliferation and Migration of Tumor Cells Through Phenylboronic Acid-Functionalized Polyamidoamine-Mediated Delivery of a Therapeutic DNAzyme Dz13 [Corrigendum].
[This corrects the article DOI: 10.2147/IJN.S211744.].


Bioanalysis and pharmacokinetics of the p38 MAPkinase inhibitor SB202190 in rats.
We have developed a sensitive and reproducible high performance liquid chromatography (HPLC)-UV method for the quantification of the p38 MAPkinase inhibitor SB202190 in serum, kidney homogenates and urine samples. Liquid-liquid extraction of SB202190 from the samples was performed using diethylether after adding a derivative of SB202190 as internal standard (I.S.). Chromatography was carried out using a C8 reversed-phase column with an isocratic mobile phase consisting of acetonitrile-water-trifluoroacetic acid (30:70:0.1, v/v/v; pH 2.0). Both drug and I.S. were measured at 350 nm and eluted at 5.0 and 10.6 min, respectively. Peak-height ratios of the drug and the I.S. were used for the quantification of SB202190 from the different matrixes. The limit of quantitation of SB202190 in serum, kidney and urine were 0.25 microg/ml, 1 microg/g and 1 microg/ml, respectively. The average recoveries were 74, 75 and 92% in serum, kidney and urine, respectively. The intra- and inter-day precision (% CV) and accuracy (% bias) were below 15% for all concentrations. The method was successfully applied for a pharmacokinetic study of SB202190 in rats.


Targeting Parasite-Produced Macrophage Migration Inhibitory Factor as an Antivirulence Strategy With Antibiotic-Antibody Combination to Reduce Tissue Damage.
Targeting virulence factors represents a promising alternative approach to antimicrobial therapy, through the inhibition of pathogenic pathways that result in host tissue damage. Yet, virulence inhibition remains an understudied area in parasitology. Several medically important protozoan parasites such as Plasmodium, Entamoeba, Toxoplasma, and Leishmania secrete an inflammatory macrophage migration inhibitory factor (MIF) cytokine homolog, a virulence factor linked to severe disease. The aim of this study was to investigate the effectiveness of targeting parasite-produced MIF as combination therapy with standard antibiotics to reduce disease severity. Here, we used Entamoeba histolytica as the model MIF-secreting protozoan, and a mouse model that mirrors severe human infection. We found that intestinal inflammation and tissue damage were significantly reduced in mice treated with metronidazole when combined with anti-E. histolytica MIF antibodies, compared to metronidazole alone. Thus, this preclinical study provides proof-of-concept that combining antiparasite MIF-blocking antibodies with current standard-of-care antibiotics might improve outcomes in severe protozoan infections.


Characterization of an extracellular α-xylosidase involved in xyloglucan degradation in Aspergillus oryzae.
α-Xylosidases release the α-D-xylopyranosyl side chain from di- and oligosaccharides derived from xyloglucans and are involved in xyloglucan degradation. In this study, an extracellular α-xylosidase, named AxyB, is identified and characterized in Aspergillus oryzae. AxyB belongs to the glycoside hydrolase family 31 and releases D-xylose from isoprimeverose (α-D-xylopyranosyl-(1 → 6)-D-glucopyranose) and xyloglucan oligosaccharides. In the hydrolysis of xyloglucan oligosaccharides (XLLG, Glc4Xyl3Gal2 nonasaccharide; XLXG/XXLG, Glc4Xyl3Gal1 octasaccharide; and XXXG, Glc4Xyl3 heptasaccharide), AxyB releases one molecule of the xylopyranosyl side chain attached to the non-reducing end of the β-1,4-glucan main chain of these xyloglucan oligosaccharides to yield GLLG (Glc4Xyl2Gal2), GLXG/GXLG (Glc4Xyl2Gal1), and GXXG (Glc4Xyl2). A. oryzae has both extracellular and intracellular α-xylosidase, suggesting that xyloglucan oligosaccharides are degraded by a combination of isoprimeverose-producing oligoxyloglucan hydrolase and intracellular α-xylosidase and a combination of extracellular α-xylosidase and β-glucosidase(s) in A. oryzae. KEY POINTS: • An extracellular α-xylosidase, AxyB, is identified in Aspergillus oryzae. • AxyB releases the xylopyranosyl side chain from xyloglucan oligosaccharides. • Different sets of glycosidases degrade xyloglucan oligosaccharides in A. oryzae.


Ecophysiology of Yucca brevifolia, an arborescent monocot of the Mojave sesert.
Photosynthetic characteristics and transpiration of Yucca brevifolia, an evergreen tree endemic to the Mojave Desert of California and Nevada, were examined in the field and the laboratory. Yucca brevifolia was confirmed to be a C3 plant, with no CAM tendencies observed for its semi-succulent leaves. The species exhibited a maximum net CO2 uptake of 12 μmol m-2 s-1 at 22°C when grown at day/night air temperatures of 31°C/17°C (data expressed on a total area basis for these opaque leaves). The optimum temperature for CO2 uptake shifted 4.5°C per 10°C change in daytime growth temperature, so that observed leaf temperatures in the field were near optimum temperatures throughout the midday period in all but the hottest months of the year. Leaves also acclimated to low and high temperature extremes, tolerances ranging to-11°C and to 59°C, respectively, suggesting that low temperatures limit the distribution of Y. brevifolia but high temperatures do not. Light saturation of photosynthesis occurred at a relatively low PAR of about 500 μmol m-2 s-1, similar to the actual PAR within a rosette. Diurnal patterns of leaf conductance shifted from a broad midday peak in wet seasons to a reduced, narrow, early morning peak in the dry season, indicating effective stomatal control of water use. The approximately 5-month-long winter-spring growth season accounted for 80% of the yearly CO2 uptake, with a predicted annual uptake of about 22 mol m-2 y-1 and a transpiration ratio of 700.


Structure of Galectin-3 bound to a model membrane containing ganglioside GM1.
Galectin-3 (Gal-3) is a β-galactosidase-binding protein involved in various biological processes, including neuronal growth and adhesion. The pairing of Gal-3 with ganglioside GM1's pentasaccharide chain at the outer leaflet of the plasma membrane, which triggers downstream cell-signaling cascades, seems to be involved in these processes. A crucial feature of Gal-3 is its ability to form oligomers and supramolecular assemblies that connect various carbohydrate-decorated molecules. Although we know the atomistic structure of Gal-3 bound to small carbohydrate ligands, it remains unclear how Gal-3 binds GM1 in a membrane. Furthermore, the influence of this interaction on Gal-3's structure and oligomeric assembly has to be elucidated. In this study, we used X-ray reflectivity (XR) from a model membrane to determine the structure and surface coverage of Gal-3 bound to a membrane containing GM1. We observed that the carbohydrate recognition domain interacts with GM1's pentasaccharide, while the N-terminal domain is pointed away from the membrane, likely to facilitate protein-protein interactions. In a membrane containing 20 mol % GM1, Gal-3 covered ∼50% of the membrane surface with one Gal-3 molecule bound per 2130 Å2. We used molecular dynamics simulations and Voronoi tessellation algorithms to build an atomistic model of membrane-bound Gal-3, which is supported by the XR results. Overall, this work provides structural information describing how Gal-3 can bind GM1's pentasaccharide chain, a prerequisite for triggering regulatory processes in neuronal growth and adhesion.


Hydronephrosis during pregnancy: a literature survey.
The occurrence of hydronephrosis and hydroureters during pregnancy has been termed physiological, inasmuch as it is seen in more than 80%, most frequently and most pronounced in primigravida. The dilatation develops during the second trimester, and becomes more prominent on the right side, is only seen above the linea terminalis and disappears within a few weeks after birth. The condition is not seen in women whose ureters do not cross the pelvic brim. The extent of the dilatation can be reduced by placing the woman on the side least affected or in the knee-elbow position. After a survey of the literature, the conclusion is reached that today there is every probability that hydronephrosis during pregnancy develops as a result of compression of the ureters between the pregnant uterus and the linea terminalis. It has not been demonstrated that the change in hormonal balance during pregnancy is of importance. The clinical significance of hydronephrosis lies in the association between ureteral obstruction and the high frequency of ascending urinary tract infection during pregnancy and in the understanding of the importance--in the treatment of infection--of improving drainage by means of a change in position. Isotope renographic studies seem to show a possible relationship between bilateral ureteral obstruction and the development of pre-eclampsia. Similarly, it appears that acute hydronephrosis or worsening of an existing hydronephrosis has been somewhat overlooked as a possible cause of uncertain abdominal pain during pregnancy. These conditions should be examined by means of ultrasonography, and an attempt at treatment by a change in position should be made. In cases of continued pain or affected renal function, treatment should consist of the insertion of a ureteral catheter.


Lipoproteins modulate growth and differentiation of cultured human epidermal keratinocytes.
The effects of various lipoproteins on the growth and the differentiation of cultured normal human keratinocytes were investigated. Primary cultures of human epidermal keratinocytes were obtained from neonatal foreskin, and then added with lipoproteins, very low density lipoprotein (VLDL), low density lipoprotein (LDL), and high density lipoprotein (HDL). Cell growth potential was examined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. VLDL and LDL enhanced keratinocytes growth and LDL receptor expression at the plasma membrane level. These effects were more remarkably observed in cells cultured with VLDL than in cells cultured with LDL. Apolipoprotein E (ApoE) was highly increased in VLDL treated cells. These results suggest that VLDL binds with high affinity to cell surface receptors and induces cell proliferation.


The impact of the 2011 US Food and Drug Administration transvaginal mesh communication on utilization of synthetic mid-urethral sling procedures.
We sought to examine the change in utilization of the midurethral sling (MUS) for the treatment of stress urinary incontinence (SUI) after the 2011 US FDA communication regarding transvaginal mesh. This is a retrospective cohort study evaluating surgical utilization of MUS at a managed care organization of 4.5 million patients from 2008 to 2016. The primary outcome was the change in utilization of synthetic mesh MUS before and after the July 2011 FDA communication. Secondary outcomes were the changes in surgeon level MUS utilization. MUS procedures decreased from 131 to 116 per 100,000 adult women with a decrease of 11.5% from 2010 to 2012. Year over year utilization of MUS was rapidly increasing (p < 0.01) prior the FDA communication from 116 (in 2008) to 131 (in 2010) per 100,000 women and then significantly declined (p < 0.01) after its release from 135 (in 2011) to 75 (in 2016) per 100,000 women (13% increase vs 44% decrease). The number of surgeons performing MUS increased (p < 0.01) from 172/year to 186/year from 2008 to 2010 (Table 1). This decreased (p < 0.01) from 183/year to 121/year from 2011 to 2016. MUS for SUI drastically declined after the FDA communication. Despite the 2011 FDA communication concerning only transvaginal mesh for pelvic organ prolapse, there was a significant decrease in MUS with synthetic mesh utilization. Our findings support the importance of continued long-term outcome data regarding the safety and efficacy of MUS and highlight the impact of the FDA warning on MUS utilization.


Knowledge of dental trauma among dental students. Lecture intervention protocol and follow-up over four academic courses.
A study was made to evaluate knowledge of dental trauma among first-year dental students at the start of the career; assess the knowledge gained immediately after a lecture intervention; and evaluate persisting knowledge on an annual basis until the fourth year of the career. The study involved 29 volunteers from the first year of dentistry (School of Dentistry, Madrid Complutense University, Madrid, Spain). All the participants completed a previously validated questionnaire including questions referred to the management of dental trauma at the site of the accident, and other related aspects. This was followed by a brief lecture on the subject, and then the same questionnaire was administered again. Completion of the original questionnaire was subsequently repeated on an annual basis up until the fourth year of the career. Repeated measures analysis was used to assess the evolution of student knowledge. Knowledge of the subject was seen to be lacking at the start of the career, but increased significantly as a result of the lecture intervention (P < .001). Over the subsequent courses, although the notions referred to dental trauma were seen to decrease with respect to the first evaluation, they remained high. All of the participants agreed on the need for informative campaigns referred to dental trauma targeted to students in the first courses of the health sciences. It is necessary to impart knowledge on the prevention and immediate management of dental traumatisms in order to improve their prognosis. This learning is especially relevant to students in the first courses of the health sciences.


Incidence and geographical distribution of patients hospitalised with fascioliasis in Spain.
The epidemiology of human fascioliasis is related to the geographical and environmental characteristics of the area where transmission occurs. There are gaps in the current knowledge of the distribution of fascioliasis in Spain. The objective of the study was to determine the incidence and geographic distribution of patients with fascioliasis who required hospitalisation in Spain. An observational study of the hospitalised population (166 patients) with a diagnosis of fascioliasis, according to the minimum basic data set (MBDS) for hospital discharge, between 1997 and 2014 was carried out. Most of the hospitals were Spanish National Health System hospitals. The incidence of hospitalised patients with fascioliasis was 2.1 (99% CI, 2.03-2.13) cases/10,000,000 inhabitants per year. The annual incidence was reduced during the 18 years of the study. The relative risk of men was 1.136 (99% CI, 0.299-0.993) with respect to women. A focal geographic aggregation of cases was observed in areas especially in northern and central Spain. The greatest incidents were found in the provinces of Segovia and Lugo. Intrahospital death occurred in 3 patients. The incidence of hospitalisations with fascioliasis in Spain is low, has been reduced and has predominated in the provinces of Segovia and Lugo.


Enhanced degradation of hydrocarbons in constructed wetlands aided with nutrients, surfactant, and aeration.
The use of constructed wetlands (CWs) is a promising approach for the remediation of hydrocarbon-polluted wastewater. The amendments of CWs with nutrients, surfactants, and aeration enhances the removal of pollutants from wastewater. The objective of the present study was to explore the effect of external stimulants, i.e., nutrients, surfactant, and aeration on hydrocarbons degradation potential of CWs. The CWs mesocosms were developed by the vegetation of Phragmites australis and amendments with nutrients (20 mg l-1 N, 2.6 mg l-1 P, and 16.4 mg l-1 K), surfactant Tween 20 (0.2%, v/v), and aeration (7 mg l-1) for the remediation of diesel-spiked water (2%, w/v). The comparative analysis showed that the addition of nutrients, surfactant, and aeration individually enhanced total petroleum hydrocarbons (TPHs) reduction, and maximum TPHs reduction (88.4%) was achieved after 60 days in the mesocosms amended with the combination of nutrients, surfactant, and aeration. Among different individual treatments, the aeration (alone) also played a pivotal role in TPHs reduction (61%). The least (12%) reduction in TPHs was achieved in the mesocosms supplied with surfactant only. This study revealed that the combined application of nutrients, surfactant, and aeration in CWs enhanced its hydrocarbons degradation performance.


Spontaneous labelling and stigma associated with clinical characteristics of peers 'at-risk' for psychosis.
The public health benefits of utilizing an 'at-risk for psychosis' designation are tempered by concerns about stigma. It is therefore of interest to examine whether symptoms associated with this designation might spontaneously induce labels associated with a psychotic disorder, other non-psychotic disorders or non-psychiatric labels. This pilot study explored the labels associated with characteristics of 'high risk for psychosis' and the corresponding stigma level. A vignette describing an identical character, followed by a series of questions about stigmatizing attitudes towards the vignette character, was administered in the present investigation. The results indicated that even though most young people (59%) did not spontaneously label the vignette character with psychotic-like diagnostic labels, the single most frequent label provided was 'paranoid/a'. When such labelling, that is, strongly tied to psychosis, occurred, respondents exhibited stronger stigmatizing attributions of fear compared to those indicating non-psychiatric labels (e.g. 'weird'). These results suggest that the majority of respondents did not endorse diagnostic labels spontaneously, thus signaling that stigma in the majority of cases would not naturalistically be elicited. However, a segment of respondents evidenced stigma simply from behavioural changes manifested by individuals exhibiting signs of psychosis, independent of diagnosis. Implications for reducing any stigma associated with an 'at-risk for psychosis' designation are discussed.


Ventricular tachycardia related to transcutaneous pacing.
A 3-year-old child with Haemophilus influenzae endocarditis and aortic route abscesses presented with sudden cardiovascular collapse. During resuscitation, the child was noted to be in complete heart block. Transcutaneous pacing was instituted three times, and ventricular dysrhythmias were associated with each pacing attempt. When pacing was discontinued, the patient spontaneously reverted to complete heart block without ventricular ectopy. An emergency thoracotomy revealed rupture of the aortic route, and the patient died during surgery. Transcutaneous pacing may precipitate serious dysrhythmias; appropriate precautions are recommended.


Erratum to: A multi-stage genome-wide association study of uterine fibroids in African Americans.
The article "A multi-stage genome-wide association study of uterine fibroids in African Americans", written by Jacklyn N. Hellwege, was originally published Online First without open access. After publication in volume 136, issue 10, page 1363-1373 the author decided to opt for Open Choice and to make the article an open access publication. Therefore, the copyright of the article has been changed to


Methods to support evidence-informed decision-making in the midst of COVID-19: creation and evolution of a rapid review service from the National Collaborating Centre for Methods and Tools.
The COVID-19 public health crisis has produced an immense and quickly evolving body of evidence. This research speed and volume, along with variability in quality, could overwhelm public health decision-makers striving to make timely decisions based on the best available evidence. In response to this challenge, the National Collaborating Centre for Methods and Tools developed a Rapid Evidence Service, building on internationally accepted rapid review methodologies, to address priority COVID-19 public health questions. Each week, the Rapid Evidence Service team receives requests from public health decision-makers, prioritizes questions received, and frames the prioritized topics into searchable questions. We develop and conduct a comprehensive search strategy and critically appraise all relevant evidence using validated tools. We synthesize the findings into a final report that includes key messages, with a rating of the certainty of the evidence using GRADE, as well as an overview of evidence and remaining knowledge gaps. Rapid reviews are typically completed and disseminated within two weeks. From May 2020 to July 21, 2021, we have answered more than 31 distinct questions and completed 32 updates as new evidence emerged. Reviews receive an average of 213 downloads per week, with some reaching over 7700. To date reviews have been accessed and cited around the world, and a more fulsome evaluation of impact on decision-making is planned. The development, evolution, and lessons learned from our process, presented here, provides a real-world example of how review-level evidence can be made available - rapidly and rigorously, and in response to decision-makers' needs - during an unprecedented public health crisis.


Inhibition of tumor growth, angiogenesis, and microcirculation by the novel Flk-1 inhibitor SU5416 as assessed by intravital multi-fluorescence videomicroscopy.
Vascular endothelial growth factor (VEGF) plays a fundamental role in mediating tumor angiogenesis and tumor growth. Here we investigate the direct effect of a novel small molecule inhibitor of the Flk-1-mediated signal transduction pathway of VEGF, SU5416, on tumor angiogenesis and microhemodynamics of an experimental glioblastoma by using intravital multifluorescence videomicroscopy. SU5416 treatment significantly suppressed tumor growth. In parallel, SU5416 demonstrated a potent antiangiogenic activity, resulting in a significant reduction of both the total and functional vascular density of the tumor microvasculature, which indicates an impaired vascularization as well as significant perfusion failure in treated tumors. This malperfusion was not compensated for by changes in vessel diameter or recruitment of nonperfused vessels. Analyses of the tumor microcirculation revealed significant microhemodynamic changes after angiogenesis blockage such as a higher red blood cell velocity and blood flow in remnant tumor vessels when compared with controls. Our results demonstrate that the novel antiangiogenic concept of targeting the tyrosine kinase of Flk-1/KDR by means of a small molecule inhibitor represents an efficient strategy to control growth and progression of angiogenesis-dependent tumors. This study provides insight into microvascular consequences of Flk-1/KDR targeting in vivo and may have important implications for the future treatment of angiogenesis-dependent neoplasms.


Radiographic factors predicting non-union of displaced intracapsular femoral neck fractures.
After 82 patients underwent osteosynthesis with multiple pinning for a displaced intracapsular femoral neck fracture, 58 fractures were united, and 24 were not. These 82 patients were included in a discriminant analysis. Union and non-union groups were the dependent variables. Eleven presumably predictive factors measured on X-ray films obtained from these patients before and immediately after operation were taken as independent variables. Three radiographic factors were selected by a stepwise method according to the effect they had on union. These were: the distance of medial displacement between fragments before reduction; the varus angle after reduction; and the distance of medial displacement between fragments after reduction. The distance of medial displacement between fragments before reduction proved the most important factor in making a choice between osteosynthesis and primary arthroplasty, and it was revealed that osteosynthesis could not be expected to provide union if the distance was 20 mm or more. It was also confirmed that union was promoted, if the cranial fragment was reduced to a valgus position and the medial cortical bones were aligned as much as possible at the time of osteosynthesis.


Dual-energy CT in assessment of thrombus perviousness and its application in predicting outcomes after intravenous thrombolysis in acute ischemic stroke.
To evaluate the feasibility of using iodine overlay maps reconstructed from dual-energy CT (DECT) to assess thrombus perviousness and investigate its value in predicting outcomes after intravenous thrombolysis in patients with acute ischemic stroke. 86 patients with proximal intracranial occlusions of the anterior circulation who underwent intravenous thrombolysis were included in this study. Thrombus iodine concentrations (ICthrombus) and normalized iodine concentrations (NICthrombus) were compared to conventional perviousness parameters (thrombus attenuation increase, TAI; void fraction, ε and CTA-index). The associations between perviousness parameters and outcomes were analyzed by Spearman's correlation and regression analysis. ICthrombus and NICthrombus were significantly correlated with conventional perviousness parameters (P < 0.001). The median ICthrombus was 6.81 (interquartile range [IQR], 4.76-8.73) mg/ml in the favorable functional outcome group, which was higher than 3.52 (IQR, 2.08-6.86) mg/ml in the unfavorable outcome group (P = 0.001). The median NICthrombus was 0.095 (IQR, 0.068-0.116) and 0.054 (IQR, 0.031-0.083) in the favorable and unfavorable outcome groups, respectively (P < 0.001). NICthrombus predicted favorable outcome with a higher area under the curve (AUC) of 0.755 than any conventional perviousness parameter (P < 0.05). In the multivariable regression model, ICthrombus was independently associated with favorable outcome (odds ratio [OR] = 1.472, 95 % CI: 1.154-1.877, P = 0.002) and successful recanalization (OR = 1.356, 95 % CI: 1.093-1.681, P = 0.006). ICthrombus was negatively correlated with the final infarct volume (FIV) (r = -0.262, P = 0.020). Results for NICthrombus were similar. DECT is of great value in assessing thrombus perviousness. NICthrombus is a meaningful predictor of stroke prognosis and recanalization after intravenous thrombolysis in acute ischemic stroke.


Cohnella sp. A01 laccase: thermostable, detergent resistant, anti-environmental and industrial pollutants enzyme.
Laccase (EC 188.8.131.52; benzenediol; oxygen oxidoreductases) is a multi-copper oxidase that catalyzes the oxidation of phenols, polyphenols, aromatic amines, and different non-phenolic substrates with concomitant reduction of O2 to H2O. Enzymatic oxidation techniques have the potential of implementation in different areas of industrial fields. In this study, the Cohnella sp. A01 laccase gene was cloned into pET-26 (b+) vector and was transformed to E. coli BL21. Then it was purified using His tag affinity (Ni sepharose resin) chromatography. The estimated molecular weight was approximately 60 kDa using SDS-PAGE. The highest enzyme activity and best pH for 2,6-dimethoxyphenol (DMP) oxidation were recorded as 8 at 90 °C respectively. The calculated half-life and kinetic values including Km, Vmax, turn over number (kcat), and catalytic efficiency (kcat/Km) of the enzyme were 106 min at 90 °C and 686 μM, 10.69 U/ml, 20.3 S-, and 0.029 s-1 μM-1, respectively. The DMP was available as the substrate in all the calculations. Enzyme activity enhanced in the presence of Cu2+, NaCl, SDS, n-hexane, Triton X-100, tween 20, and tween 80, significantly. The binding residues were predicted and mapped upon the modeled tertiary structure of identified laccase. The remaining activity and structural properties of Cohnella sp. A01 laccase in extreme conditions such as high temperatures and presence of metals, detergents, and organic solvents suggest the potential of this enzyme in biotechnological and industrial applications. This process has been patented in Iranian Intellectual Property Centre under License No: 91325.


MR-based conductivity imaging using multiple receiver coils.
To propose a signal combination method for MR-based tissue conductivity mapping using a standard clinical scanner with multiple receiver coils. The theory of the proposed method is presented with two practical approaches, a coil-specific approach and a subject-specific approach. Conductivity maps were reconstructed using the transceive phase of the combined signal. The sensitivities of the coefficients used for signal combination were analyzed and the method was compared with other signal combination methods. For validation, multiple receiver brain coils and multiple receiver breast coils were used in phantom, in vivo brain, and in vivo breast studies. The variation among the conductivity estimates was <15% as determined by the coefficient sensitivity tests. Compared with other signal combination methods, the proposed method yielded fewer artifacts in the conductivity estimates. MR-based tissue conductivity mapping is feasible when using a standard clinical MR scanner with multiple receiver coils. The proposed method reduces systematic errors in phase-based conductivity mapping that can occur due to the inhomogeneous magnitude of the combined receive profile. Magn Reson Med 76:530-539, 2016. © 2015 Wiley Periodicals, Inc.


Assessing Energy Requirements in Women With Polycystic Ovary Syndrome: A Comparison Against Doubly Labeled Water.
Weight loss is prescribed to offset the deleterious consequences of polycystic ovary syndrome (PCOS), but a successful intervention requires an accurate assessment of energy requirements. Describe energy requirements in women with PCOS and evaluate common prediction equations compared with doubly labeled water (DLW). Cross-sectional study. Academic research center. Twenty-eight weight-stable women with PCOS completed a 14-day DLW study along with measures of body composition and resting metabolic rate and assessment of physical activity by accelerometry. Total daily energy expenditure (TDEE) determined by DLW. TDEE was 2661 ± 373 kcal/d. TDEE estimated from four commonly used equations was within 4% to 6% of the TDEE measured by DLW. Hyperinsulinemia (fasting insulin and homeostatic model assessment of insulin resistance) was associated with TDEE estimates from all prediction equations (both r = 0.45; P = 0.02) but was not a significant covariate in a model that predicts TDEE. Similarly, hyperandrogenemia (total testosterone, free androgen index, and dehydroepiandrosterone sulfate) was not associated with TDEE. In weight-stable women with PCOS, the following equation derived from DLW can be used to determine energy requirements: TDEE (kcal/d) = 438 - [1.6 * Fat Mass (kg)] + [35.1 * Fat-Free Mass (kg)] + [16.2 * Age (y)]; R2 = 0.41; P = 0.005. Established equations using weight, height, and age performed well for predicting energy requirements in weight-stable women with PCOS, but more precise estimates require an accurate assessment of physical activity. Our equation derived from DLW data, which incorporates habitual physical activity, can also be used in women with PCOS; however, additional studies are needed for model validation.


Structure of the calcium-rich signature domain of human thrombospondin-2.
Thrombospondins (THBSs) are secreted glycoproteins that have key roles in interactions between cells and the extracellular matrix. Here, we describe the 2.6-A-resolution crystal structure of the glycosylated signature domain of human THBS2, which includes three epidermal growth factor-like modules, 13 aspartate-rich repeats and a lectin-like module. These elements interact extensively to form three structural regions termed the stalk, wire and globe. The THBS2 signature domain is stabilized by these interactions and by a network of 30 bound Ca(2+) ions and 18 disulfide bonds. The structure suggests how genetic alterations of THBSs result in disease.


In vitro effects of photobiomodulation on cell migration and gene expression of ALP, COL-1, RUNX-2, and osterix in cementoblasts.
The aim of this study was to evaluate the effects of photobiomodulation (PBM) on cell migration and alkaline phosphatase (ALP), type I collagen (Col-1), runt-related transcription factor 2 (RUNX-2), and Osterix (OSX) gene expression in a cementoblast culture (OCCM-30), in a microenvironment mimicking an injury on the cementoblast layer, such as it occurs during root resorption. For this, OCCM-30 cells were cultured in 6-well plates and the following parameters were assayed: (1) migration by scratch assay and ALP, Col-1, Runx2, and Osx by real-time PCR. PBM was performed in two protocols using a LED device emitting light at 660 nm (± 30 nm). OCCM-30 cementoblasts were grown and divided into four groups: (1) negative control; (2) positive control (scratch); (3) scratch + PBM with a total energy of 36 J and energy density 1.6 J/cm2; and (4) scratch + PBM with a total energy of 72 J and energy density of 3.2 J/cm2. Data were statistically analyzed, with the level of significance set at 5%. Cementoblasts migrated from the edge of the scratch toward the center, and the wound closed after 24 h, with the PBM3.2J/cm2 group showing the higher cell migration compared with the other groups at 2 h, 6 h, 8 h, and 13 h (p < 0.05). The control and PBM1.6J/cm2 groups showed similar levels of cell migration, with no significant differences (p > 0.05). PBM3.2J/cm2 group exhibited greater ALP, Col-1, OSX, and RUNX2 in comparison with the other experimental groups (p < 0.05). Similar levels of all genes evaluated were observed between the PBM1.6J/cm2 group and the positive control group (p > 0.05). In conclusion, our findings support the effectiveness of photobiomodulation on cementoblast migration and gene expression, which may contribute to the formation of a new cementum layer.


Effect of treatment of dentofacial deformities on the electromyographic activity of masticatory muscles.
Individuals with dentofacial deformities present changes in masticatory muscles. The objective of the present study was to determine the influence of interdisciplinary treatment in cases of class III dentofacial deformities regarding the EMG activity of the temporal (T) and masseter (M) muscles. The study was conducted on 15 patients with class III dentofacial deformities who were submitted to orthodontic, oromyofunctional and surgical treatment and assigned to groups P1 (before surgery) and P2 (6-9 months after surgery). Fifteen individuals with no alterations in facial morphology or dental occlusion and without signs or symptoms of temporomandibular joint dysfunction were used as controls (CG). The T and M muscles were submitted to EMG bilaterally in the situations of mastication and mastication plus biting, with analysis of amplitude interval and root mean square. For all muscles tested, there was a difference between CG, P1 and P2; CG was higher than P2 and P2 higher than P1 in all situations assessed. We conclude that there was an increase in EMG activity in the T and M muscles after surgical correction of the dentofacial deformity accompanied by interdisciplinary treatment, although the values were still lower than those obtained for CG.


Sigma receptors in schizophrenic cerebral cortices.
Antipsychotics represent high affinity for sigma receptors and sigma-like drugs often have the psychotomimetic properties. Besides, the receptors are unevenly distributed in human brain. These findings suggest that sigma receptors might be involved in the pathophysiology of schizophrenia. Sigma receptors in rat and human brain were measured with [3H]-1, 3, di-o-tolylguanidine (DTG) and non-specific binding of [3H]DTG was determined in the presence of 10(-5)M haloperidol. Monovalent and divalent cations strongly inhibited [3H]DTG binding. Glutamate, aspartate and glycine also decreased the binding to human cerebral membranes. With post-mortem brain samples from 12 schizophrenics and 10 controls, sigma receptors were measured in 17 areas of cerebral cortex. Sigma receptors binding showed the regional differences in the cortex, but no significant differences between schizophrenics and controls were observed except the superior parietal cortex where the binding significantly increased in the schizophrenic group. These results suggest that sigma receptors in cerebral cortices might not be directly concerned with the pathophysiological role in schizophrenia.


Irritability and mental health profiles among children and adolescents: A result of latent profile analysis.
Irritability is a transdiagnostic symptom that accompanies both internalizing and externalizing problems. However, there has been a scarcity of research concerning the relationships between irritability and mental health profiles among children and adolescents. This study aimed to identify latent profiles in children and adolescents using anxiety, depression, oppositionality, and irritability. In addition, the profiles were further examined in their relationships with mental health symptoms. The study analyzed data from 1867 children and adolescents aged 6-15 years from the COVID-19 Online-Survey for Children and Adolescents in Japan (J-COSCA). Parent-reported questionnaires were used in this study. A latent profile analysis detected five latent profiles. High oppositionality characterized the first profile ("oppositional": n = 405, 22%). High levels of depression and other less pronounced symptoms characterized the second profile ("depressed": n = 276, 15%). The third profile ("average": n = 602, 33%) presented average symptoms of anxiety, depression and oppositionality and low irritability. The fourth profile ("well-adjusted": n = 235, 13%) presented low values for all the applicable symptoms. The last profile ("comorbid": n = 308, 17%) exhibited high values for all the symptoms and the highest level of irritability of the five profiles. We analyzed the data from a community sample alone after capturing it using parent-reported questionnaires. This study revealed that the five profiles (oppositional, depressed, average, well-adjusted, and comorbid) were identified, and children and adolescents in the comorbid profiles had high irritability as well as high anxiety, depression, and oppositionality.


Enantioselective synthesis of a key intermediate of 20(S)-camptothecin via an enzyme-catalyzed resolution.
The key intermediate of a 20(S)-camptothecin 1 synthesis was obtained in a highly enantioselective fashion using an enzyme-catalyzed resolution. A commercially available protease was found to exhibit the highest enantioselectivity with moderate activity, and (S)-ethyl 2-acetoxy-2-[6-(acetoxymethyl)-1,1-(ethylenedioxy)-5-oxo- 1,2,3,5-tetrahydroindolizin-7-yl]butanoate 7c of 98% e.e. was obtained as the remaining substrate.


Treatment-resistant depression: resistant to definition?
To better define treatment-resistant depression (TRD) so as to assist clinical management and refine treatment guidelines. In this study, we examine a broad range of clinical variables in depressed patients (n=196) referred to a tertiary referral Mood Disorders Unit (MDU). Information was collected from patients, referrers and assessors over a period of 32 months and included evaluations of treatments, treatment resistance and related variables. Data were analysed across trichotomized 'high', 'low' and 'no' treatment resistance groupings of patients. A significantly greater proportion of patients with melancholia were amongst the high TRD group, and this was consistent across different strategies for evaluating melancholia. Melancholia perhaps provides a prototypic TRD subset that perhaps reflects some innate aspects of melancholic depression or factors such as the impact of ageing. Research into TRD is needed to both replicate this finding and perhaps explicate it further.


Suicide attempt with a kitchen knife.
Penetrating trauma to the abdomen can be a potential diagnostic dilemma for the trauma surgeon, and a formal exploratory laparotomy may result in the detection of occult injuries. We report a very unusual case of penetrating trauma to the abdomen resulting in pericardio-diagphragmatic rupture. We have also highlighted the technical aspects of clinical care in this specific scenario.


The mRNA and protein levels of the glycolytic enzymes lactate dehydrogenase A (LDHA) and phosphofructokinase platelet (PFKP) are good predictors of survival time, recurrence, and risk of death in cervical cancer patients.
Patients with cervical cancer (CC) may experience local recurrence very often after treatment; when only clinical parameters are used, most cases are diagnosed in late stages, which decreases the chance of recovery. Molecular markers can improve the prediction of clinical outcome. Glycolysis is altered in 70% of CCs, so molecular markers of this pathway associated with the aggressiveness of CC can be identified. The expression of 14 glycolytic genes was analyzed in 97 CC and 29 healthy cervical tissue (HCT) with microarray; only LDHA and PFKP were validated at the mRNA and protein levels in 36 of those CC samples and in 109 new CC samples, and 31 HCT samples by qRT-PCR, Western blotting, or immunohistochemistry. A replica analysis was performed on 295 CC from The Cancer Genome Atlas (TCGA) database. The protein expression of LDHA and PFKP was associated with poor overall survival [OS: LDHA HR = 4.0 (95% CI = 1.4-11.1); p = 8.0 × 10-3 ; PFKP HR = 3.3 (95% CI = 1.1-10.5); p = 4.0 × 10-2 ] and disease-free survival [DFS: LDHA HR = 4.5 (95% CI = 1.9-10.8); p = 1.0 × 10-3 ; PFKP HR = 3.2 (95% CI = 1.2-8.2); p = 1.8 × 10-2 ] independent of FIGO clinical stage, and the results for mRNA expression were similar. The risk of death was greater in patients with overexpression of both biomarkers than in patients with advanced FIGO stage [HR = 8.1 (95% CI = 2.6-26.1; p = 4.3 × 10-4 ) versus HR = 7 (95% CI 1.6-31.1, p = 1.0 × 10-2 )] and increased exponentially as the expression of LDHA and PFKP increased. LDHA and PFKP overexpression at the mRNA and protein levels was associated with poor OS and DFS and increased risk of death in CC patients regardless of FIGO stage. The measurement of these two markers could be very useful for evaluating clinical evolution and the risk of death from CC and could facilitate better treatment decision making.


Advanced physico-chemical treatment experiences on young municipal landfill leachates.
In this study, Membrane Filtration (UF+RO), Struvite (MAP) precipitation and ammonia stripping alternatives were studied on biologically pre-treated Landfill Leachate. The results indicated that the system including the Upflow Anaerobic Sludge Blanket Reactor (UASBR) and Membrane Reactors (UF+RO) has been offered as an appropriate treatment alternative for young landfill leachates. This system provided high removals of COD, colour and conductivity (>98-99%). For ammonia removal, struvite precipitation was applied at the stoichiometric ratio (Mg:NH4:PO4=1:1:1) to anaerobically pre-treated raw landfill leachate effluent having an influent ammonium concentration of 2240 mg/l. Maximum ammonium nitrogen removal was observed as 85% at pH of 9.2. In ammonia stripping following 2 h of aeration, the removal was 72% at pH=12 while the removals were around 20% at pH=10 and pH=11. When membrane reactor, and struvite precipitation or ammonia stripping was applied to anaerobically pre-treated effluents, the results indicated that each system could be used as an appropriate post-treatment option for young landfill leachates. In economic aspect, ammonia stripping was found as the cheapest alternative with high ammonium removal. However, when both high COD and ammonium removals were to be achieved membrane technology such as UF+RO (SW) could be considered as the most appropriate system due to the fact that COD removal could be obtained very low by ammonia stripping.


Effects of mitofusin-2 gene on cell proliferation and chemotherapy sensitivity of MCF-7.
In order to evaluate the effect of mitofusin-2 gene (mfn2) on proliferation and chemotherapy sensitivity of human breast carcinoma cell line MCF-7 in vitro, pEGFPmfn2 plasmid carrying full length of mitofusin-2 gene was transfected, by using sofast, into MCF-7 cells. Mitofusin-2 gene expression in MCF-7 cells transfected by sofast after 48 h was detected by PCR and Western blotting, and the stable expression of GFP protein in MCF-7 cells by Western blot analysis. The proliferation of MCF-7 cells was assayed by MTT and cell counting. By using PI method, the effects of mfn2 on the cell cycle distribution of MCF-7 were measured. Annexin-V/PI double labeling method was employed to detect the changes in apoptosis induced by chemotherapeutics before and after transfection. The results showed that the MCF-7 cells transfected with mfn2 gene could stably and highly express GFP protein. MTT assay revealed that after transfection of mfn2 cDNA, the proliferation of MCF-7 cells was significantly inhibited. DNA histogram showed that cells arrested in S phase, and the percentage of S phase cells was 42.7, 17.2 and 19.6 in mfn2 cDNA transfection group, blank plasmid transfection group and blank control group, respectively (P<0.05). The apoptosis ratio of the cells transfected with mfn2 gene was increased from 3.56% to 15.95%, that of the cells treated with camptothecin (CAMP) followed by mfn2 gene transfection was 69.6%, and that in blank plasmid transfection group and blank control group was 31.0% and 23.4% respectively (P<0.05). It was suggested that transfection of mfn2 gene could significantly inhibit the proliferation of MCF-7 cells and promote their sensitivity to CAMP with a synergic effect.


Exciton-polaritons in van der Waals heterostructures embedded in tunable microcavities.
Layered materials can be assembled vertically to fabricate a new class of van der Waals heterostructures a few atomic layers thick, compatible with a wide range of substrates and optoelectronic device geometries, enabling new strategies for control of light-matter coupling. Here, we incorporate molybdenum diselenide/hexagonal boron nitride (MoSe2/hBN) quantum wells in a tunable optical microcavity. Part-light-part-matter polariton eigenstates are observed as a result of the strong coupling between MoSe2 excitons and cavity photons, evidenced from a clear anticrossing between the neutral exciton and the cavity modes with a splitting of 20 meV for a single MoSe2 monolayer, enhanced to 29 meV in MoSe2/hBN/MoSe2 double-quantum wells. The splitting at resonance provides an estimate of the exciton radiative lifetime of 0.4 ps. Our results pave the way for room-temperature polaritonic devices based on multiple-quantum-well van der Waals heterostructures, where polariton condensation and electrical polariton injection through the incorporation of graphene contacts may be realized.


Long-term results following pediatric distal forearm fractures.
The purpose of this retrospective study was to investigate the frequency and extent of clinical and radiological late sequelae and to identify predicting factors. A total of 220 patients of growing age with 232 closed, conservatively treated fractures were re-examined clinically and radiologically at a median follow-up time of 10 years (range 5-16 years). Clinical and radiological findings were summarised as an overall result. Of the total of patients, 19% reported pain in the injured wrist, and wrist mobility was limited in 5% of patients. Forearm rotation was decreased in 16%, primarily in epiphyseal separation of the ulna ( p=0.0033). Radial inclination was different in 6% of patients, palmar tilt in 2%, and ulnar variance in 37%, compared with the contralateral side. Ulnocarpal impaction syndrome was present in 75% of the patients with positive ulnar variance. Overall outcome was excellent in 72%, good in 19%, moderate in 6%, and poor in 3% of patients. The younger the children were at the time of injury, the more favourable the results were ( p=0.009). Children who were older than 10 years when they suffered a severe fracture dislocation had the poorest results ( p=0.008). Further factors having a negative influence on outcome were repeated reduction maneuvers and an additional fracture of the ulna. Our follow-up examinations showed that the majority of patients achieved good results, especially in children under 10 years old. Large dislocations at the time of fracture healing do not influence long-term results in this age group and thus can be tolerated. Patients over 10 years old, whose fractures healed with an angular deformity of more than 20 degrees and/or fragment dislocation over half the breadth of the shaft showed the poorest results. Thus, such dislocations should not be tolerated, and reduction should be attempted in this age group by only one reduction maneuver.


Recovery of manganese and zinc from waste Zn-C cell powder: Mutual separation of Mn(II) and Zn(II) from leach liquor by solvent extraction technique.
Acidic organophosphorous extractants were screened for the mutual separation of Mn(II) and Zn(II), in a leach solution of waste Zn-C cell powder. This was done using a 2mol/L H2SO4 solution containing 2g/L glucose. Extraction characteristics of both metal ions in this mixture have been examined as functions of equilibrium pH. Although tech. and anal. grade D2EHPA are not so effective for the separation, PC88A, Cyanex 272, Cyanex 302 and Cyanex 301 are all promising for this purpose. Strippings of Mn(II) and Zn(II) from the extracted organic phases have been examined, using 0.25, 0.50 and 1mol/L H2SO4; and 1mol/L HCl, HNO3 and HClO4 at different phase ratios. H2SO4 appears to be the best stripping agent. A 1mol/L H2SO4 solution strips almost 100% of target metal ions in 10min, regardless of the extractant used. As ΔpH1/2=2.75 and as the max. separation factor (β)=1793 for Cyanex 302 at pH(eq)=4.0, a flow sheet has been developed for their mutual separations. Finally, classical precipitation methods have been adopted to obtain MnS and ZnS, which can be easily oxidized to MnO2 and ZnO, respectively.


Phakomatosis pigmentovascularis IIb with hypoplasia of the inferior vena cava and the right iliac and femoral veins causing recalcitrant stasis leg ulcers.
We present a patient with phakomatosis pigmentovascularis (PPV) type IIb accompanied with venous hypoplasia, from the inferior vena cava to the superficial femoral vein. Although it is not obvious whether this vascular anomaly, which is probably congenital, is coincidental or not, it is possible that the 2 diseases have some relationship each other, because PPV is thought to result from abnormal vasomotor activity during the embryonic period. In the diagnosis of type II PPV, careful examination and several studies are required to determine systemic involvement that may include large vessel changes.


The importance of individual frequencies of endogenous brain oscillations for auditory cognition - A short review.
Oscillatory EEG activity in the human brain with frequencies in the gamma range (approx. 30-80Hz) is known to be relevant for a large number of cognitive processes. Interestingly, each subject reveals an individual frequency of the auditory gamma-band response (GBR) that coincides with the peak in the auditory steady state response (ASSR). A common resonance frequency of auditory cortex seems to underlie both the individual frequency of the GBR and the peak of the ASSR. This review sheds light on the functional role of oscillatory gamma activity for auditory processing. For successful processing, the auditory system has to track changes in auditory input over time and store information about past events in memory which allows the construction of auditory objects. Recent findings support the idea of gamma oscillations being involved in the partitioning of auditory input into discrete samples to facilitate higher order processing. We review experiments that seem to suggest that inter-individual differences in the resonance frequency are behaviorally relevant for gap detection and speech processing. A possible application of these resonance frequencies for brain computer interfaces is illustrated with regard to optimized individual presentation rates for auditory input to correspond with endogenous oscillatory activity. This article is part of a Special Issue entitled SI: Auditory working memory.


Reproductive aspects in spinal cord injured males.
Infertility in paraplegic males is determined by two major factors: (1) most patients with spinal cord lesions cannot ejaculate, and (2) if ejaculation is possible, then the features of the semen are constantly abnormal. Various methods have been proposed to stimulate the ejaculatory reflex in paraplegics. From 1983 we have used for this purpose a simple vibrator applied to the penis and with this method the ejaculatory response was obtained in 72 of 102 patients treated. Fifteen patients who desired a child, received instruction in self-using the vibrator at home weekly. Sperm characteristics were evaluated (mean of two samples) before and after 3 months of self-use of the vibrator. Statistical evaluation of the results was performed with Student t-test. At the end of the treatment an improvement of sperm concentration and progressive motility was evident, but the result of highest statistical significance was the decrease of abnormal sperm morphology. Three couples obtained a pregnancy with AIH.


Micronutrients in gastrointestinal cancer.
The monitoring of micronutrients and the relationship between dietary intake and micronutrient status prior to and after surgery in patients with histologically proven gastrointestinal adenocarcinoma, both weight-stable and weight-losing (> 7.5% of their pre-illness weight) has been studied and the results compared to controls. Plasma vitamin C and red blood cell thiamine levels were significantly lower in weight-losing cancer patients when compared to their weight-stable counterparts (P < 0.05 and P < 0.02 respectively). Weight-losing patients had a lower vitamin C (P < 0.05) and thiamine (P < 0.002) intake, and a higher elevation in plasma C-reactive protein and a lower prealbumin level (P < 0.02), when compared to both weight-stable cancer patients and controls. Plasma vitamin C, prealbumin and C-reactive protein levels remained unchanged after curative resections of the tumours compared to a preoperative value, and there was a highly significant correlation between plasma vitamin C and dietary intake of vitamin C. This study suggests that the lower vitamin C and thiamine status in weight-losing gastrointestinal cancer patients prior to surgery is due to a lower micronutrient intake and an acute phase response to their illness. Dietary intake of vitamin C appears to be the major factor in determining plasma vitamin C concentration following curative surgical resection.


Quality of life of older gynecologic oncology patients at the initiation of chemotherapy.
To evaluate older gynecologic oncology patients' quality of life (QOL) at the initiation of chemotherapy and compare their QOL scores with a female age-matched general population (GP) sample. Cross-sectional. Older (n = 122) gynecologic oncology patients completed the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30) that evaluates global health and five functional scales (range from 0 to 100). Differences in QOL scores between our sample and the GP were evaluated using one-sample t-tests and effect sizes were calculated using Cohen's d. Patients' mean age was 70.7 years (±6.6). Mean scores for the function scales ranged from 58.5 (±31.1) for role function to 86.1 (±17.0) for cognitive function. Compared to the GP, our sample reported significantly lower scores for global health status, social, role and physical functioning, and a significantly higher score for cognitive functioning. No differences were found in emotional functioning scores. No patient or public contribution.


Socioeconomic and health-related inequalities in major depressive symptoms among older adults: a Wagstaff's decomposition analysis of data from the LASI baseline survey, 2017-2018.
To find out the association between socioeconomic and health status and depression among older adults and explore the contributing factors in the socioeconomic and health-related inequalities in late-life depression. A cross-sectional study was conducted using large representative survey data. Data for this study were derived from the baseline wave of the Longitudinal Ageing Study in India conducted during 2017-2018. The effective sample size was 30 888 older adults aged 60 years and above. The outcome variable in this study was depression among older adults. Descriptive statistics along with bivariate analysis was conducted to report the preliminary results. Multivariable binary logistic regression analysis and Wagstaff's decomposition were used to fulfil the objectives of the study. There was a significant difference for the prevalence of depression (4.3%; p<0.05) among older adults from poor (11.2%) and non-poor categories (6.8%). The value of the Concentration Index was -0.179 which also confirms that the major depression was more concentrated among poor older adults. About 38.4% of the socioeconomic and health-related inequality was explained by the wealth quintile for major depression among older adults. Moreover, about 26.6% of the inequality in major depression was explained by psychological distress. Self-rated health (SRH), difficulty in activities of daily living (ADL) and instrumental ADL (IADL) contributed 8.7%, 3.3% and 4.8% to the inequality, respectively. Additionally, region explained about 23.1% of inequality followed by life satisfaction (11.2) and working status (9.8%) for major depression among older adults. Findings revealed large socioeconomic and health-related inequalities in depression in older adults which were especially pronounced by poor household economy, widowhood, poor SRH, ADL and IADL difficulty, and psychological distress. In designing prevention programmes, detection and management of older adults with depression should be a high priority, especially for those who are more vulnerable.


Perinatal and obstetric outcomes of dichorionic vs trichorionic triplet pregnancies.
Clinical management and outcome of multiple gestation can be affected by chorionicity. In triplet pregnancies, fetal death has been associated with dichorionic (DC) and monochorionic placentation. Studies evaluating triplet pregnancy outcomes in relation to chorionicity have been few and may not reflect contemporary antenatal and neonatal care. The objective of this study was to compare obstetric and perinatal outcomes in DC and trichorionic (TC) triplet pregnancies. We performed a retrospective cohort study of triplet pregnancies that delivered at ≥20 weeks' gestation at 2 Chicago area hospitals from January 1999 through December 2010. Chorionicity was determined by pathology specimen. Maternal and infant charts were reviewed for obstetric and perinatal outcomes. The study population included 159 pregnancies (477 neonates) of which 108 were TC (67.9%) and 51 were DC (32.1%). Over 94% of mothers in this study had all 3 infants survive to discharge regardless of chorionicity. No difference was found in perinatal mortality rate between DC and TC triplets (3.3% vs 4.6%; P = .3). DC triplets were significantly more likely to be very low birthweight (41.8% vs 22.2%; odds ratio, 2.2; 95% confidence interval, 1.2-4.2; P = .02) and to deliver at <30 weeks (25.5% vs 8.3%; odds ratio, 6.1; 95% confidence interval, 1.9-19.4; P = .002) compared to TC triplets. Criteria for twin-twin transfusion syndrome (TTTS) were present in 3 DC triplet pregnancies (5.9%). Neonates in pregnancies complicated by TTTS were less likely to survive 28 days as compared to neonates from DC pregnancies that were not affected by TTTS (P = .02) or TC neonates (P = .02) Neonatal survival was similar in DC pregnancies not affected by TTTS and TC pregnancies (98.6% and 96.6%; P = .7). Although perinatal mortality did not correlate with chorionicity, DC pregnancies were more likely to deliver <30 weeks' gestational age and have very low birthweight neonates. Neonatal mortality appears to be mediated by the presence or absence of TTTS as 28-day survival was worse in DC pregnancies complicated by TTTS, but similar between DC pregnancies not affected by TTTS and TC pregnancies.


Reproductive hormones and interleukin-6 in serious leisure male athletes.
Lifestyles associated with different types and intensities of exercise result in improved health including positive changes in chronic low-grade inflammatory biomarkers. Alternatively, some forms of exercise adversely affect reproductive health of men, including changes in circulating reproductive hormones. To explore the associations between exercise intensity and circulating levels of reproductive hormones, and inflammatory analytes in serious leisure athletes (triathletes and cyclists) and recreational athletes. Male athletes 18-60 years old, 16 triathletes, 46 cyclists and 45 recreational athletes, were recruited to provide plasma for the measurement of total testosterone, estradiol, follicular stimulating hormone, luteinizing hormone (LH), sex hormone-binding globulin (SHBG), cortisol, interleukin-6 (IL-6), and interleukin-1β (IL-1β) levels, and calculation of free androgen index (FAI) and the estradiol:SHBG ratio (ESR). Plasma estradiol concentrations were more than two times higher in cyclists than in triathletes and recreational athletes (p < 0.01). Testosterone levels were also higher in cyclists than recreational athletes (p < 0.01), but not significantly different from triathletes. SHBG levels were higher in triathletes and cyclists than in recreational athletes (p < 0.01). LH levels were lower in cyclists than in recreational athletes (p < 0.05). IL-6 and IL-1β levels were each two times lower in triathletes than in cyclists (p < 0.05) and IL-6 levels were lower in cyclists than in recreational athletes (p < 0.01). IL-1β levels were two times lower in triathletes than in cyclists (p < 0.05). Circulating estradiol and testosterone levels were elevated in serious leisure male cyclists. This effect is discussed in light in the absence of a substantial concomitant change in gonadotropin levels and other variables.


What is public health? a scoping review.
during the last hundred years, several major public health issues have already afflicted humanity. Most frequently cited definitions of public health have stemmed from long-standing definitions, which raises several concerns including whether these definitions can respond to today's public health challenges. The present study aimed to identify and review available public health definitions in the first place. in this scoping review, we undertook an electronic search in four databases (PubMed, Web of Science, Embase, and EBSCOhost) from inception until June 06, 2022, and a grey literature search in Google Scholar. Moreover, reference lists of publications included in the scoping review were screened manually for additional relevant publications. All types of scientific publications, in English, that focused on the definition of public health and provided an original definition were included. Year, type, disciplinary fields of publications, objectives of publications, and public health definitions were extracted. 5651 publications were identified through the scoping search, of which five were subjected to full-text review. Of these publications, two were included. An additional nine publications were identified through the manual screening. A total 11 of publications were included in the scoping review. Of the 11 definitions included in this review, the latest original definitions date back to about two decades ago. there is a noticeable lack of updated definitions of public health. Considering our findings and the ever-changing nature of public health issues, there is an urgent need for re-assessing and updating public health definitions.