Formaldehyde may be found in cosmetic products even when unlabelled.
Concomitant contact allergy to formaldehyde and formaldehyde-releasers remains common among patients with allergic contact dermatitis. Concentration of free formaldehyde in cosmetic products within allowed limits have been shown to induce dermatitis from short-term use on normal skin. The aim of this study was to investigate the formaldehyde content of cosmetic products made in Lithuania. 42 samples were analysed with the chromotropic acid (CA) method for semi-quantitative formaldehyde determination. These included 24 leave-on (e.g., creams, lotions) and 18 rinse-off (e.g., shampoos, soaps) products. Formaldehyde releasers were declared on the labels of 10 products. No formaldehyde releaser was declared on the label of the only face cream investigated, but levels of free formaldehyde with the CA method was >40 mg/ml and when analysed with a high-performance liquid chromatographic method - 532 ppm. According to the EU Cosmetic directive, if the concentration of formaldehyde is above 0.05% a cosmetic product must be labelled "contains formaldehyde". It could be difficult for patients allergic to formaldehyde to avoid contact with products containing it as its presence cannot be determined from the ingredient labelling with certainty. The CA method is a simple and reliable method for detecting formaldehyde presence in cosmetic products.


The short amino acid sequence Pro-His-Ser-Arg-Asn in human fibronectin enhances cell-adhesive function.
Synergistic sites in the central cell-adhesive domain of fibronectin (FN) substantially enhance cell adhesion mediated by the alpha 5 beta 1 integrin receptor for fibronectin. We characterized a critical minimal sequence needed for synergistic activity using site-directed mutagenesis and homology scanning using intramolecular chimeras. The minimal cell-binding domain of FN consisting of the 9th and 10th type III FN repeat was expressed in an Escherichia coli expression system. This protein retained high biological activity when assayed using a competitive inhibition assay for FN-mediated adhesion of baby hamster kidney or HT-1080 cells. In contrast, a construct consisting of the 8th and 10th repeat displayed very low biological activity. By replacing various portions of the 8th repeat with homologous 9th repeat segments, we mapped the synergistic region to the center of the 9th repeat. When a very short peptide sequence, Pro-His-Ser-Arg-Asn (PHSRN), from the 9th repeat was substituted for the homologous pentapeptide site in the 8th repeat sequence, the recombinant protein showed markedly enhanced activity. Further mutagenesis analysis suggested that the arginine residue of this pentapeptide sequence is important for function. We also identified a weaker adjacent synergy region other than the PHSRN region. Epitope mapping of an anti-FN monoclonal antibody that inhibits FN-mediated adhesion identified the same critical regions. A synthetic peptide containing the PHSRN sequence showed neither competitive inhibitory activity in solution nor synergy with a soluble RGD-containing peptide. However, when the same synthetic peptide was positioned via a covalent bond at the corresponding site of the normally inactive 8th repeat, it mediated an enhancement of adhesive activity. These results identify a pentapeptide site that synergistically enhances the cell-adhesive activity of the FN RGD sequence.


Reinforcement-Learning-Based Disturbance Rejection Control for Uncertain Nonlinear Systems.
This article investigates the reinforcement-learning (RL)-based disturbance rejection control for uncertain nonlinear systems having nonsimple nominal models. An extended state observer (ESO) is first designed to estimate the system state and the total uncertainty, which represents the perturbation to the nominal system dynamics. Based on the output of the observer, the control compensates for the total uncertainty in real time, and simultaneously, online approximates the optimal policy for the compensated system using a simulation of experience-based RL technique. Rigorous theoretical analysis is given to show the practical convergence of the system state to the origin and the developed policy to the ideal optimal policy. It is worth mentioning that the widely used restrictive persistence of excitation (PE) condition is not required in the established framework. Simulation results are presented to illustrate the effectiveness of the proposed method.


Reconstruction of lateral knee joint stability following resection of proximal fibula tumors.
Managing tumors of the proximal fibula may require en bloc resection of the fibular head with the attachment site of the lateral collateral ligament (LCL) and biceps femoris tendon. The aim of the present study was to evaluate knee stability and the Musculoskeletal Tumor Society (MSTS) functional score of patients with proximal fibula tumors. Twenty-nine patients with proximal fibula tumors were retrospectively reviewed (18 patients in the reconstruction group and 11 patients in the non-reconstruction group). A comparative analysis was conducted of knee stability (measuring the degree of lateral joint space opening using varus stress radiographs with a 30º knee flexion) and MSTS functional score between the two groups. The mean follow-up period was 42.8±20.9 months (range 24-117) and 40.8±26.0 months (range 24-117) for the reconstruction and the non-reconstruction groups, respectively. Fifteen patients (83.3%) in the reconstruction group had a stable knee, one (5.6%) had grade 1 instability and two (11.1%) had grade 2 instability. Four patients (36.4%) in the non-reconstruction group had a stable knee, three (27.3%) had grade 1 instability, one (9.1%) had grade 2 instability and three (27.3%) had grade 3 instability. Patients who underwent reconstructive surgery exhibited a higher rate of knee stability compared with those in the non-reconstruction group (P<0.05). The MSTS function scores were 93% (range, 93-100%) for the reconstruction group and 87% (range, 60-100%) for the non-reconstruction group (P<0.05). Reconstruction of the LCL and biceps femoris tendon to the lateral tibial metaphysis with a suture anchor was a safe, reliable and simple technique following resection of proximal fibula tumors.


Patient experiences of outcomes of bariatric surgery: a systematic review and qualitative synthesis.
Although bariatric surgery is the most effective treatment for severe and complex obesity, less is known about its psychosocial impact. This systematic review synthesizes qualitative studies investigating the patient perspective of living with the outcomes of surgery. A total of 2,604 records were screened, and 33 studies were included. Data extraction and thematic synthesis yielded three overarching themes: control, normality and ambivalence. These were evident across eight organizing sub-themes describing areas of life impacted by surgery: weight, activities of daily living, physical health, psychological health, social relations, sexual life, body image and eating behaviour and relationship with food. Throughout all these areas, patients were striving for control and normality. Many of the changes experienced were positive and led to feeling more in control and 'normal'. Negative changes were also experienced, as well as changes that were neither positive nor negative but were nonetheless challenging and required adaptation. Thus, participants continued to strive for control and normality in some aspects of their lives for a considerable time, contributing to a sense of ambivalence in accounts of life after surgery. These findings demonstrate the importance of long-term support, particularly psychological and dietary, to help people negotiate these challenges and maintain positive changes achieved after bariatric surgery.


Evidence of Notch-Hesr-Nrf2 Axis in Muscle Stem Cells, but Absence of Nrf2 Has No Effect on Their Quiescent and Undifferentiated State.
Nrf2 is a master regulator of oxidative stresses through the induction of anti-oxidative genes. Nrf2 plays roles in maintaining murine hematopoietic stem cells and fly intestinal stem cells. The canonical Notch signaling pathway is also crucial for maintaining several types of adult stem cells including muscle stem cells (satellite cells). Here, we show that Dll1 induced Nrf2 expression in myogenic cells. In addition, primary targets of Notch signaling, Hesr1 and Hesr3, were involved in the up-regulation of Nrf2 mRNA and expression of its target genes. In vitro, Nrf2 had anti-myogenic and anti-proliferative effects on primary myoblasts. In vivo, although Nrf2-knockout mice showed decreased expression of its target genes in muscle stem cells, adult muscle stem cells of Nrf2-knockout mice did not exhibit the phenotype. Taken together, in muscle stem cells, the Notch-Hesr-Nrf2 axis is a pathway potentially inducing anti-oxidative genes, but muscle stem cells either do not require Nrf2-mediated anti-oxidative gene expression or they have a complementary system compensating for the loss of Nrf2.


In Times of Adversity: A Neuroscience Perspective on Stress, Health, and Implications for Society Post-pandemic.
The relationship between chronic stress and chronic disease (including mental illness) is well established: HPA-axis hyperactivity leads to hormonal dysregulation of primary mediators (eg, glucocorticoids, cytokines, etc.), allostatic overload, and neurological degradation, followed by clinical manifestations of disease. Amid the largest public health crisis of the century lay a myriad of challenges pushing people beyond their limit. From experiencing loss of connection or dealing with loss of life to financial shocks of COVID-19 lockdowns or infection by the SARS-CoV-2 virus, stress is at an all-time high, threatening both brain and mental health at scale. Fortunately, there is a way forward: the neuroscience of resilience teaches us that it is possible to resist, recover, and redirect the brain from trauma to re-establish balance in the body and improve well-being. At the same time, health follows a social gradient: adverse and protective psychosocial factors are shaped by wider social and economic determinants of health. This paper argues the neurobiology of stress is not separate from health disparities linked to adverse factors (ie, stress) created by complex social and economic contexts. Therefore, the field of neuroscience is challenged to inform multi-context and multi-level approaches and engage with decision-makers to enact policies and interventions aimed at promoting the resilient element in a wider population health context. Undoubtedly, achieving such a goal for current and future generations to benefit and lead healthier lives requires a heroic effort from all key stakeholders. The cost of willful neglect to resolve these issues is too expensive.


The Arabidopsis extracellular UNUSUAL SERINE PROTEASE INHIBITOR functions in resistance to necrotrophic fungi and insect herbivory.
Protease inhibitors (PIs) function in the precise regulation of proteases, and are thus involved in diverse biological processes in many organisms. Here, we studied the functions of the Arabidopsis UNUSUAL SERINE PROTEASE INHIBITOR (UPI) gene, which encodes an 8.8 kDa protein of atypical sequence relative to other PIs. Plants harboring a loss-of-function UPI allele displayed enhanced susceptibility to the necrotrophic fungi Botrytis cinerea and Alternaria brassicicola as well as the generalist herbivore Trichoplusia ni. Further, ectopic expression conferred increased resistance to B. cinerea and T. ni. In contrast, the mutant has wild-type responses to virulent, avirulent and non-pathogenic strains of Pseudomonas syringae, thus limiting the defense function of UPI to necrotrophic fungal infection and insect herbivory. Expression of UPI is significantly induced by jasmonate, salicylic acid and abscisic acid, but is repressed by ethylene, indicating complex phytohormone regulation of UPI expression. The upi mutant also shows significantly delayed flowering, associated with decreased SOC1 expression and elevated levels of MAF1, two regulators of floral transition. Recombinant UPI strongly inhibits the serine protease chymotrypsin but also weakly blocks the cysteine protease papain. Interestingly, jasmonate induces intra- and extracellular UPI accumulation, suggesting a possible role in intercellular or extracellular functions. Overall, our results show that UPI is a dual-specificity PI that functions in plant growth and defense, probably through the regulation of endogenous proteases and/or those of biotic invaders.


Concentration-effect relationship for antimicrobial drugs.
The many relevant pharmacokinetic aspects influencing the relationship between antimicrobial drug concentration in the blood and at infection site with their pharmacodynamic effects are discussed, with particular regard to rules upon which clinical treatment modalities are based.


Ureteric obstruction complicating Crohn's disease in the terminal ileum.
Ureteric obstruction complicating Crohn's disease of the terminal ileum is reported in three patients. This complication is treacherous, since symptoms of urinary tract disease are mostly absent, as is laboratory evidence of urinary tract infection. It is concluded that inflammatory ureteral engagement should always be suspected in patients with Crohn's disease, particularly when located in the terminal ileum. A preoperative intravenous pyelography should be included as a routine procedure in these patients. The detection of ureteral obstruction is a strong indication for early operative treatment of the disease. Ureterolysis combined with intestinal resection is recommended. The ureteral involvement, which is most likely a late phenomenon of the disease, could provably be avoided if surgical treatment is instituted at an earlier stage of the disease.


A Unified Strategy to Access 2- and 4-Deoxygenated Sugars Enabled by Manganese-Promoted 1,2-Radical Migration.
The selective manipulation of carbohydrate scaffolds is challenging due to the presence of multiple, nearly chemically indistinguishable O-H and C-H bonds. As a result, protecting-group-based synthetic strategies are typically necessary for carbohydrate modification. Here we report a concise semisynthetic strategy to access diverse 2- and 4-deoxygenated carbohydrates without relying on the exhaustive use of protecting groups to achieve site-selective reaction outcomes. Our approach leverages a Mn2+-promoted redox isomerization step, which proceeds via sugar radical intermediates accessed by neutral hydrogen atom abstraction under visible light-mediated photoredox conditions. The resulting deoxyketopyranosides feature chemically distinguishable functional groups and are readily transformed into diverse carbohydrate structures. To showcase the versatility of this method, we report expedient syntheses of the rare sugars l-ristosamine, l-olivose, l-mycarose, and l-digitoxose from commercial l-rhamnose. The findings presented here validate the potential for radical intermediates to facilitate the selective transformation of carbohydrates and showcase the step and efficiency advantages attendant to synthetic strategies that minimize a reliance upon protecting groups.


Diagnosis of Splenic Lymphoma by Endoscopic Ultrasound Guided Fine Needle Aspiration: A Case Report and Review of the Literature.
Introduction. Splenic tumor is usually found as an incidental finding on CT of abdomen. Traditionally, ultrasound (US) or computed tomography (CT) guided biopsies were employed for the purpose of sampling; however they have been reported to have a complication rate of 5.3%. Endoscopic ultrasound-fine needle aspiration (EUS-FNA) has been recently utilized for the purpose of sampling splenic tumors. In literature there are 7 reported instances where splenic lymphoma was diagnosed using EUS-FNA. We present a case of follicular B cell lymphoma of the spleen diagnosed using EUS-FNA. Case Report. 58-year-old female presented to her primary care physician for left upper quadrant abdominal pain for one week. Physical exam was significant for left upper quadrant tenderness. Her laboratory tests were within normal limits. She underwent CT scan of abdomen which revealed approximately 5 cm × 5 cm mass in spleen. EUS-FNA of the spleen revealed a large hypoechoic, heterogeneous, well-demarcated mass measuring 54.7 mm × 43.0 mm. Fine needle aspiration was performed, and the sample was submitted for cytology and flow cytometry. Flow cytometry revealed a lambda monotypic population of B cells displaying dim CD19 and CD10. Diagnosis of B cell non-Hodgkin low grade follicular lymphoma was made. Conclusion. Endoscopic ultrasound with fine needle aspiration is a very rare but safe, reliable method of diagnosis of splenic lymphomas.


A proteomic study of Shengmai injection's mechanism on preventing cardiac ischemia-reperfusion injury via energy metabolism modulation.
Energy metabolism modulation plays an important role in protecting the heart from ischemia-reperfusion (IR) injury. Shengmai injection (SMI) is a Chinese medicine, which is widely used in China to treat ischemic heart diseases with speculated functions of modulating energy metabolism. To uncover the molecular mechanisms underlying the cardioprotective activity of SMI via the modulation of energy metabolism, a proteomic analysis was performed on ischemia-reperfusion (IR) injured hearts of rats in this study. Two-dimensional gel electrophoresis (2-DE) was used to measure the protein expression profiles of heart tissues. Differentially expressed proteins among groups were identified using matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS/MS). Western blot analysis was used to validate differentially expressed proteins. Proteomic data revealed 14 major differentially expressed proteins that are related to the energy metabolism. It was found that the glucose oxidation, TCA cycle and ATP synthesis related proteins were consistently up-regulated in SMI treated rats, which is beneficial to aerobic respiration and ATP generation. In contrast, two proteins catalyzing fatty acid β-oxidation were down-regulated, implying the inhibition of this pathway to avoid high oxygen consumption. It is thus concluded that one of the major mechanisms of SMI protection against IR injury was modulation of the myocardial energy metabolism to improve cardiac efficiency through multiple metabolic pathways including stimulating glucose metabolism and inhibiting fatty acid metabolism. It provided potential protein targets for the therapeutic strategy through modulation of the myocardial energy metabolism.


Analysis of environmental dust in goat and sheep farms to assess Coxiella burnetii infection in a Q fever endemic area: Geographical distribution, relationship with human cases and genotypes.
Real-time PCR analysis of environmental samples (dust and aerosols) is an easy tool to investigate the presence of Coxiella burnetii in the farm environment. The aim of this study was to assess the distribution of C. burnetii DNA in dust collected inside animal premises from 272 small ruminant farms in Bizkaia (northern Spain), a region with recent reports of human Q fever cases and outbreaks. Within each farm, 5 samples of dust were collected from difference surfaces, and data on animal census, management procedures, characteristics of the premises and geographic location were collected. Real-time PCR analysis of the dust samples detected presence of C. burnetii DNA in 98 farms (36.0%), flock-prevalence being higher in sheep (38.9%) or mixed ovine-caprine production systems (36.8%), compared to goats (25.0%). Larger bacterial burdens were observed in mixed farms, compared to sheep (p < .05). Single nucleotide polymorphism (SNP) analysis identified 5 different genotypes, with SNP8 being the predominant genotype (73%), followed by SNP6 (11%), SNP2 (9%), SNP4 (5%) and SNP1 (2%). Proportion of farms where C. burnetii DNA was detected differed among the different agricultural counties, and a higher proportion of C. burnetii DNA positive farms was associated with the occurrence of recent human Q fever outbreaks at several geographical locations. Dust sampling in domestic ruminant farms coupled with real-time PCR to screen for the presence of C. burnetii and estimate bacterial load can be a useful tool to identify herds and regions with high prevalence, define priority actions and monitor the effect of control measures. If combined with molecular genotyping and spatial distribution maps, it can help to identify farm contamination sources and trace the origin of human outbreaks.


Estimating the size of "anti-vax" and vaccine hesitant populations in the US, UK, and Canada: comparative latent class modeling of vaccine attitudes.
Vaccine hesitancy is a significant impediment to global efforts to vaccinate against the SARS-CoV-2 virus at levels that generate herd immunity. In this article, we show the utility of an inductive approach - latent class analysis (LCA) - that allows us to characterize the size and nature of different vaccine attitude groups; and to compare how these groups differ across countries as well as across demographic subgroups within countries. We perform this analysis using original survey data collected in the US, UK, and Canada. We also show that these classes are strongly associated with SARS-CoV-2 vaccination intent and perceptions of the efficacy and safety of the COVID-19 vaccines, suggesting that attitudes about vaccines to fight the novel coronavirus pandemic are well explained by latent vaccine attitudes that precede the pandemic. More specifically, we find four substantive classes of vaccine attitudes: strong supporters, supporters with concerns, vaccine hesitant, and "anti-vax" as well as a fifth measurement error class. The strong "anti-vax" sentiment class is small in all three countries, while the strong supporter class is the largest across all three countries. We observe different distributions of class assignments in different demographic groups - most notably education and political leaning (partisanship and ideology).


Incidence of Nelson's syndrome after adrenalectomy for Cushing's disease in children: results of a nationwide survey.
To establish the incidence of Nelson's syndrome in children treated with total bilateral adrenalectomy (TBA) for Cushing's disease, a survey was made of members of The Lawson Wilkins Pediatric Endocrine Society. Thirty-one patients aged 10 months to 16 years had been treated with TBA for Cushing's disease; one had been treated with ortho para prime isomer of dichlorodiphenyldichloroethane alone. Postadrenalectomy hyperpigmentation was reported in 18 patients. Sella enlargement was detected in eight patients (25%) after 1 to 5.5 years (mean, three years) post-TBA. Five of these patients have had documented pituitary adenomas to date. This incidence is higher than the adult figure of 10% to 16%.


Synthesis of β- and γ-hydroxy α-amino acids via enzymatic kinetic resolution and cyanate-to-isocyanate rearrangement.
A new strategy for stereoselective preparation of all four isomers of β- and γ-hydroxy α-amino acids is presented. The developed procedure is based on enzymatic kinetic resolution and cyanate-to-isocyanate rearrangement as key steps. Stereocontrol is achieved by proper choice of the starting hydroxyacid, the course of kinetic resolution, and the stereospecific sigmatropic rearrangement step, which proceeds with full chirality transfer.


A coumarin based gold(i)-alkynyl complex: a new class of supramolecular hydrogelators.
A phosphine-gold(i)-alkynyl-coumarin complex, [Au{7-(prop-2-ine-1-yloxy)-1-benzopyran-2-one}(DAPTA)] (), was synthesized and the formation of long luminescent fibers in solution was characterized via fluorescence microscopy and dynamic light scattering. The fibers presented strong blue and green luminescence, suggesting that the gold(i) in the complex increased intersystem crossing due to the heavy atom effect, resulting in a significant increase in triplet emission. The X-ray structure of the fibers indicates that both aurophilic, π-π interactions and hydrogen bonding contribute to their formation in aqueous solvents.


Radiologic findings that mimic malignancy.
The purpose of this pictorial essay is to describe selected variant anatomy, benign pathology, and posttreatment appearances that may be incorrectly attributed to malignancy at cancer investigation. Radiologists involved in cancer staging should be aware of benign imaging appearances that simulate malignancy. Failure to correctly identify these findings as such may lead to unnecessary patient anxiety, incorrect tumor staging, and inappropriate treatment.


Managing a massacre: savagery, civility, and gender in Moro Province in the wake of Bud Dajo.
This article examines the delicate ideological maneuverings that shaped American colonial constructions of savagery, civility, and gender in the wake of the Bud Dajo massacre in the Philippines's Muslim south in 1906. It looks particularly at shifting notions of femininity and masculinity as these related to episodes of violence and colonial control. The article concludes that, while the Bud Dajo massacre was a terrible black mark on the American military's record in Mindanao and Sulu, colonial officials ultimately used the event to positively affirm existing discourses of power and justification, which helped to sustain and guide military rule in the Muslim south for another seven years.


Association of CYP2E1 and NAT2 polymorphisms with lung cancer susceptibility among Mongolian and Han populations in the Inner Mongolian region.
To explore associations of CYP2E1 and NAT2 polymorphisms with lung cancer susceptibility among Mongolian and Han populations in the Inner Mongolian region. CYP2E1 and NAT2 polymorphisms were detected by PCR-RFLP in 930 lung cancer patients and 1000 controls. (1) Disequilibrium of the distribution of NAT2 polymorphism was found in lung cancer patients among Han and Mongolian populations (p=0.031). (2) Lung cancer risk was higher in individuals with c1, D allele of CYP2E1 RsaI/PstI, DraI polymorphisms and slow acetylation of NAT2 (c1 compared with c2, OR=1.382, 95%CI: 1.178- 1.587, p=0.003; D compared with C, OR=1.241, 95%CI: 1.053-1.419, P<0.001; slow acetylation compared with rapid acetylation, OR=1.359, 95%CI:1.042-1.768, p=0.056) (3) Compared with c2/c2 and rapid acetylation, c1/c1 together with slow acetylation synergetically increased risk of lung cancer 2.83 fold. (4) Smokers with CYP2E1 c1/c1, DD, and NAT2 slow acetylation have 2.365, 1.916, 1.841 fold lung cancer risk than others with c2/c2, CC and NAT2 rapid acetylation, respectively. (5) Han smokers with NAT2 slow acetylation have 1.974 fold lung cancer risk than others with rapid acetylation. Disequilibrium distribution of NAT2 polymorphism was found in lung cancer patients among Han and Mongolian populations. Besides, Han smokers with NAT2 slow acetylation may have higher lung cancer risk compared with rapid acetylation couterparts. CYP2E1 c1/ c1, DD and NAT2 slow acetylation, especially combined with smoking, contributes to the development of lung cancer. CYP2E1 c1/c1 or DD genotype and NAT2 slow acetylation have strong synergistic action in increasing lung cancer risk.


Quantitative analysis of nanoscale intranuclear structural alterations in hippocampal cells in chronic alcoholism via transmission electron microscopy imaging.
Chronic alcoholism is known to alter the morphology of the hippocampus, an important region of cognitive function in the brain. Therefore, to understand the effect of chronic alcoholism on hippocampal neural cells, we employed a mouse model of chronic alcoholism and quantified intranuclear nanoscale structural alterations in these cells. Transmission electron microscopy (TEM) images of hippocampal neurons were obtained, and the degree of structural alteration in terms of mass density fluctuation was determined using the light-localization properties of optical media generated from TEM imaging. The results, which were obtained at length scales ranging from ~30 to 200 nm, show that 10-12 week-old mice fed a Lieber-DeCarli liquid (alcoholic) diet had a higher degree of structural alteration than control mice fed a normal diet without alcohol. The degree of structural alteration became significantly distinguishable at a sample length of ~100 nm, which is the typical length scale of the building blocks of cells, such as DNA, RNA, proteins and lipids. Interestingly, different degrees of structural alteration at such length scales suggest possible structural rearrangement of chromatin inside the nuclei in chronic alcoholism.


Photodetachment and photofragmentation pathways in the [(CO2)2(H2O)m]- cluster anions.
The mass-selected [(CO(2))(2)(H(2)O)(m)](-) cluster anions are studied using a combination of photoelectron imaging and photofragment mass spectroscopy at 355 nm. Photoelectron imaging studies are carried out on the mass-selected parent cluster anions in the m=2-6 size range; photofragmentation results are presented for m=3-11. While the photoelectron images suggest possible coexistence of the CO(2) (-)(H(2)O)(m)CO(2) and (O(2)CCO(2))(-)(H(2)O)(m) parent cluster structures, particularly for m=2 and 3, only the CO(2) (-) based clusters are both required and sufficient to explain all fragmentation pathways for m>/=3. Three types of anionic photofragments are observed: CO(2) (-)(H(2)O)(k), O(-)(H(2)O)(k), and CO(3) (-)(H(2)O)(k), k</=m, with their yields varying depending on the parent cluster size. Of these, only CO(2) (-)(H(2)O)(k) can potentially result from (O(2)CCO(2))(-)(H(2)O)(m) parent structures, although an alternative mechanism, involving the dissociation and recombination of the CO(2) (-) cluster core, is possible as well. The O(-)(H(2)O)(k) and CO(3) (-)(H(2)O)(k) channels are believed to be triggered by the dissociation of the CO(2) (-) cluster core. In the CO(3) (-)(H(2)O)(k) channel, seen only in the range of m=3-6, the CO(2) (-) core dissociation is followed by an intracluster association of nascent O(-) with the solvent CO(2). This channel's absence in larger clusters (m>6) is attributed to hindrance from the H(2)O molecules.


Morphologic characteristics of pulmonary macrophages in cetaceans: particular reference to pulmonary intravascular macrophages as a newly identified type.
We examined the morphologic characteristics of pulmonary macrophages in 42 specimens of Odontoceti (Globicephala macrorhynchus, Grampus griseus, Tursiops truncatus, Stenella attenuata, Stenella coeruleoalba, Berardius bairdii), using light and electron microscopes as well as immunohistochemistry with SRA-E5. SRA-E5-positive alveolar macrophages and pulmonary interstitial macrophages contained graphitic soots, indicating the clearance of airborne, aspirated foreign bodies. Pulmonary intravascular macrophages (PIMs), positive with SRA-E5, were present within pulmonary capillaries, attaching to applied endothelial cells by cell junctions. They showed cytoplasmic tubular structures of micropinocytosis vermiformis and erythrophagocytosis, indicating their contributory role in the clearance of blood-borne particles. The uptake of pathogens by PIMs may be associated with the inducement of acute lung injury, especially bacterial infectious pneumonia. This study revealed for the first time the presence of PIMs in cetaceans.


PM sources in a highly industrialised area in the process of implementing PM abatement technology. Quantification and evolution.
Principal component analysis (PCA) coupled with a multilinear regression analysis (MLRA) was applied to PM(10) speciation data series (2002-2005) from four sampling sites in a highly industrialised area (ceramic production) in the process of implementing emission abatement technology. Five common factors with similar chemical profiles were identified at all the sites: mineral, regional background (influenced by the industrial estate located on the coast: an oil refinery and a power plant), sea spray, industrial 1 (manufacture and use of glaze components, including frit fusion) and road traffic. The contribution of the regional background differs slightly from site to site. The mineral factor, attributed to the sum of several sources (mainly the ceramic industry, but also with minor contributions from soil resuspension and African dust outbreaks) contributes between 9 and 11 microg m(-3) at all the sites. Source industrial 1 entails an increase in PM(10) levels between 4 and 5 microg m(-3) at the urban sites and 2 microg m(-3) at the suburban background site. However, after 2004, this source contributed less than 2 microg m(-3) at most sites, whereas the remaining sources did not show an upward or downward trend along the study period. This gradual decrease in the contribution of source industrial 1 coincides with the implementation of PM abatement technology in the frit fusion kilns of the area. This relationship enables us to assess the efficiency of the implementation of environmental technologies in terms of their impact on air quality.


[The role of the Academy of Science in health care during the war in Bosnia and Herzegovina].
Academy of science and art of RBH with its section for medical science (OMN) took part in health protection during this war. Its way of working was in organisation of science work in medicine and direct science-researching work. The Academy was coorganizator 5 great project and direct realizator of three. First group are projects called war projects: 1) Surgery, 2) Psychiatrics, 3) Social medicine, 4) Refugees, 5) Internal medicine. Second group: 1) Therapy of poisoning, 2) Galen medicine, 3) Circulation. Although the Academy had many other activities, most important activity is about health protection in war. Some members of OMN took part in activities like science researching, medical education, important parts of health protection and consultations. In medical researching science observations, descriptions and classifications, and some researching should be noticed in this kind of war and isolation. Concerning the science discoveries it is definite and formulate and ready publications of polytraumatism, treating with oxygenation solutions mass therapy, new doctrines etc. We also got experiences for medical education, its changing and consider about theory, practice and opinion. It is necessary for medical worker to know that health protection is defence of war desert, and not the way of war and its weapon. Earlier warnings of some philosophers, and their self-killing prognoses are going on and started in BIH. War is not only between people, but with nature and spirit and world cataclysm is very near. Activity of health protection people give us some hope, because there are men who will try to stop destroying. They defended the dignity of their profession and other educated people.(ABSTRACT TRUNCATED AT 250 WORDS)


Mucocutaneous lymph node syndrome in Arizona.
Mucocutaneous lymph node syndrome (MLNS) is a newly recognized entity, widely prevalent in Japan. It has also been reported in Korea, Hawaii, and Greece. We have recently seen four white children, 3 to 4 1/2 years of age, with MLNS, in Tucson, Ariz. They had all the principal signs and symptoms characteristic of MLNS.


Telemetric detection of cardiac allograft rejection. Correlation of electrophysiological, histological, and biochemical changes during unmodified rejection.
Intra-abdominal mismatched heterotopic cardiac allograft transplantation without immunosuppression was performed in eight pigs. Postoperatively, daily electrophysiological studies were carried out either with exteriorized temporary epicardial pacing wires (n = 4) or by a telemetrically controlled implanted pacemaker connected to permanent epicardial pacing leads (n = 4). Electrophysiological studies data were correlated with histopathologic and biochemical findings from daily myocardial biopsies. Electrophysiological studies revealed no significant alteration of sinus or atrioventricular node function, refractoriness, or ventricular pacing threshold. However, ventricular voltage amplitude, measured through the electrodes, decreased steadily with time in all donor hearts and was significantly correlated with histopathologic rejection grade (p less than 0.001) and with adenosine 5'-triphosphate (ATP) depletion (p less than 0.001). Ventricular voltage amplitude less than 75% of baseline occurred 4.5 +/- 1.5 days after transplantation, and this decreased voltage amplitude coincided with a moderate to severe (Grade 2 or 3) histological rejection pattern with a sensitivity of 89% (17 of 19) and a specificity of 77% (17 of 22). Similar changes in voltage amplitude were not found in control hearts. Myocardial tissue ATP values fell significantly from control values with early (Grade 1) rejection (p less than 0.05). Evidence for oxygen free radical injury was indicated by a rise in conjugated dienes of free fatty acids; this increase in diene level occurred 4.3 +/- 1.2 days postoperatively and then regressed during the terminal stages.(ABSTRACT TRUNCATED AT 250 WORDS)


Amorphouslike diffraction pattern in solid metallic titanium.
Amorphouslike diffraction patterns of solid elemental titanium have been detected under high pressure and high temperature using in situ energy-dispersive x-ray diffraction and a multianvil press. The onset pressure and the temperature of formation of amorphous titanium is found to be close to the alpha-beta-omega triple point in the P-T phase diagram. Amorphous Ti has been found to be thermally stable up to 1250 degrees C for at least 3 min at some pressures. By analyzing the conditions for producing amorphous elemental Zr and Ti, we observed a multi-phase-point amorphization phenomenon for preparing single-element bulk amorphous metals. The results reported may open a new way to preparing single-element bulk amorphous metals with a high thermal stability.


Isolation, nucleotide sequence, and expression of a cDNA encoding pig citrate synthase.
Citrate synthase is a key enzyme of the Krebs tricarboxylic acid cycle and catalyzes the stereospecific synthesis of citrate from acetyl coenzyme A and oxalacetate. The amino acid sequence and three-dimensional structure of pig citrate synthase dimers are known, and regions of the enzyme involved in substrate binding and catalysis have been identified. A cloned complementary DNA sequence encoding pig citrate synthase has been isolated from a pig kidney lambda gt11 cDNA library after screening with a synthetic oligonucleotide probe. The complete nucleotide sequence of the 1.5-kilobase cDNA was determined. The coding region consists of 1395 base pairs and confirms the amino acid sequence of purified pig citrate synthase. The derived amino acid sequence of pig citrate synthase predicts the presence of a 27 amino acid N-terminal leader peptide whose sequence is consistent with the sequences of other mitochondrial signal peptides. A conserved amino acid sequence in the mitochondrial leader peptides of pig citrate synthase and yeast mitochondrial citrate synthase was identified. To express the pig citrate synthase cDNA in Escherichia coli, we employed the inducible T7 RNA polymerase/promoter double plasmid expression vectors pGP1-2 and pT7-7 [Tabor, S., & Richardson, C. C. (1985) Proc. Natl. Acad. Sci. U.S.A. 82, 1074-1078]. The pig citrate synthase cDNA was modified to delete the N-terminal leader sequence; then by use of a synthetic oligonucleotide linker, the modified cDNA was cloned into pT7-7 immediately following the initiator Met. A glutamate-requiring (citrate synthase deficient), recA- E. coli mutant, DEK15, was transformed with pGP1-2 and then pT7-7PCS. pT7-7PCS complemented the E. coli gltA mutation.(ABSTRACT TRUNCATED AT 250 WORDS)


Nuances in transcanal endoscopic approach to benign middle ear tumours in adult patients.
Minimally invasive surgery of benign middle ear tumours is possible by using the endoscope. The optimal lighting and the broadest vision it offers, allow a transcanal approach to these rare tumours. The objective of this work is to summarize its key points through a case series. Retrospective study of benign middle ear tumours that underwent exclusive endoscopic surgery in a third-level adult university hospital between June 2018 and June 2020. Postoperative follow-up was performed by otoendoscopy and audiometry. Six patients underwent surgery during the study period. Five patients were female and one male, with an average age of 57.8 years (± 21.9). Four tumours were in the left ear and 2 in the right ear. These included 4tympanic paragangliomas (3 type I and one type II), a chorda tympani neuroma, and a congenital cholesteatoma. There were no serious postoperative complications. At present, no tumour recurrence has been found in either case, with a minimum follow-up of 7 months. The present study adds evidence on the safety and efficacy of endoscopic transcanal ear surgery, as a minimally invasive technique, for the treatment of benign middle ear tumours confined to the tympanic cavity.


Patient and provider perceptions of the relationship between alcohol use and TB and readiness for treatment: a qualitative study in South Africa.
Unhealthy alcohol use is widespread in South Africa and has been linked to tuberculosis (TB) disease and poor treatment outcomes. This study used qualitative methods to explore the relationship between TB and alcohol use during TB treatment. Focus groups (FGs) were conducted with 34 participants who had previous or current drugsusceptible TB and self-reported current alcohol use. Eight interviews were conducted with healthcare workers who provide TB services in Worcester, South Africa. In this rural setting, heavy episodic drinking is normalized and perceived to be related to TB transmission and decreased adherence to TB medication. Both healthcare workers and FG participants recommended the introduction of universal screening, brief interventions, and referral to specialized care for unhealthy alcohol use. However, participants also discussed barriers to the provision of these services, such as limited awareness of the link between alcohol and TB. Healthcare workers also specified resource constraints while FG participants or patients mentioned widespread stigma towards people with alcohol concerns. Both FG participants and health providers would benefit from education on the relationship between TB and unhealthy alcohol use as well and had specific recommendations about interventions for alcohol use reduction. Healthcare workers also suggested that community health worker-delivered interventions could support access to and engagement in both TB and alcohol-related services. Findings support strengthening accessible, specialized services for the identification and provision of interventions and psychosocial services for unhealthy alcohol use among those with TB.


Can we use C-reactive protein levels to predict severe infection or sepsis in severely burned patients?
This is a large cohort analysis in severely burned pediatric children to determine whether C-reactive protein (CRP) can be used as a predictor for severe infection or sepsis. Nine-hundred eighteen pediatric burn patients were enrolled in this study. CRP values were measured throughout acute hospitalization and for up to 6 months postburn. Demographic data, incidence of infection, surgical interventions and other relevant clinical information was compiled from medical records. We performed an extensive literature search to identify models that other groups have developed to determine the effects of CRP levels postburn to assess the value of these parameters as predictors of sepsis or severe infection. Statistical analysis was performed using ANOVA and regression analysis where appropriate. Three-hundred fifteen female and 603 male pediatric patients were enrolled in this study. Average total body surface area (TBSA) burn was 45±23%, with full thickness burn over 32±27% TBSA, and patients were 7±6 years old. CRP values significantly correlated with burn size, survival and gender. Significantly higher levels of CRP were found in large burns, in non-survivors, and in females, p<0.05. Using various described models to determine whether CRP levels change before and after an event can predict sepsis or severe infection, we found that CRP cannot predict severe infection or sepsis. Although CRP is a marker of the inflammatory response postburn, CRP fails to predict infection or sepsis in severely burn patients.


STAT3 in cancer: A double edged sword.
The transcription factor signal transducer and activator of transcription (STAT) 3 is activated downstream of cytokines, growth factors and oncogenes to mediate their functions under both physiological and pathological conditions. In particular, aberrant/unrestrained STAT3 activity is detected in a wide variety of tumors, driving multiple pro-oncogenic functions. For that, STAT3 is widely considered as an oncogene and is the object of intense translational studies. One of the distinctive features of this factor is however, its ability to elicit different and sometimes contrasting effects under different conditions. In particular, STAT3 activities have been shown to be either pro-oncogenic or tumor-suppressive according to the tumor aetiology/mutational landscape, suggesting that the molecular bases underlining its functions are still incompletely understood. Here we discuss some of the properties that may provide the bases to explain STAT3 heterogeneous functions, and in particular how post-translational modifications contribute shaping its sub-cellular localization and activities, the cross talk between these activities and cell metabolic conditions, and finally how its functions can control the behaviour of both tumor and tumor microenvironment cell populations.


Localization of antigens in thin sections of bacteria by the immuno-peroxidase technique.
The immunoperoxidase technique together with electron microscopy has been examined for the ultrastructural localization of staphylococcal protein A, the immunoferritin method being included for comparison. The results show that protein A is uniformly distributed in the whole cell wall. Both the direct and indirect methods, Fab- as well as Fc-reactions, showed identical results. tthe immunoperoxidase method was superior to the immunoferritin method, especially when applied to thin sections of the bacteria, and the clear specificity demonstrated indicates a useful method for localization of cellular antigens.


Sterols from Mytilidae show anti-aging and neuroprotective effects via anti-oxidative activity.
For screening anti-aging samples from marine natural products, K6001 yeast strain was employed as a bioassay system. The active mussel extract was separated to give an active sterol fraction (SF). SF was further purified, and four sterol compounds were obtained. Their structures were determined to be cholesterol (CHOL), brassicasterol, crinosterol, and 24-methylenecholesterol. All compounds showed similar anti-aging activity. To understand the action mechanism involved, anti-oxidative experiments, reactive oxygen species (ROS) assays, and malondialdehyde (MDA) tests were performed on the most abundant compound, CHOL. Results indicated that treatment with CHOL increases the survival rate of yeast under oxidative stress and decreases ROS and MDA levels. In addition, mutations of uth1, skn7, sod1, and sod2, which feature a K6001 background, were employed and the lifespans of the mutations were not affected by CHOL. These results demonstrate that CHOL exerts anti-aging effects via anti-oxidative stress. Based on the connection between neuroprotection and anti-aging, neuroprotective experiments were performed in PC12 cells. Paraquat was used to induce oxidative stress and the results showed that the CHOL and SF protect the PC12 cells from the injury induced by paraquat. In addition, these substance exhibited nerve growth factor (NGF) mimic activities again confirmed their neuroprotective function.


Universal Verification Methodology Based Register Test Automation Flow.
In today's SoC design, the number of registers has been increased along with complexity of hardware blocks. Register validation is a time-consuming and error-pron task. Therefore, we need an efficient way to perform verification with less effort in shorter time. In this work, we suggest register test automation flow based UVM (Universal Verification Methodology). UVM provides a standard methodology, called a register model, to facilitate stimulus generation and functional checking of registers. However, it is not easy for designers to create register models for their functional blocks or integrate models in test-bench environment because it requires knowledge of SystemVerilog and UVM libraries. For the creation of register models, many commercial tools support a register model generation from register specification described in IP-XACT, but it is time-consuming to describe register specification in IP-XACT format. For easy creation of register model, we propose spreadsheet-based register template which is translated to IP-XACT description, from which register models can be easily generated using commercial tools. On the other hand, we also automate all the steps involved integrating test-bench and generating test-cases, so that designers may use register model without detailed knowledge of UVM or SystemVerilog. This automation flow involves generating and connecting test-bench components (e.g., driver, checker, bus adaptor, etc.) and writing test sequence for each type of register test-case. With the proposed flow, designers can save considerable amount of time to verify functionality of registers.


Recent advances in phytochemistry and pharmacology of C21 steroid constituents from Cynanchum plants.
Cynanchum is one of the most important genera in Asclepiadaceae family, which has long been known for its therapeutic effects. In this genus, 16 species are of high medicinal value. The extracts of the root and/or rhizome parts have been applied in traditional Chinese medicines (TCM) for the prevention and treatment of various illnesses for centuries. C21 steroids, as the typical constituents of Cynanchum species, possess a variety of structures and pharmacological activities. This review summarizes the comprehensive information on phytochemistry and pharmacology of C21 steroid constituents from Cynanchum plants, based on reports published between 2007 and 2015. Our aim is to provide a rationale for their therapeutic application, and to discuss the future trends in research and development of these compounds. A total of 172 newly identified compounds are reviewed according to their structural classifications. Their in vitro and in vivo pharmacological studies are also reviewed and discussed, focusing on antitumor, antidepressant, antifungal, antitaging, Na(+)/K(+)-ATPase inhibitory, appetite suppressing and antiviral activities. Future research efforts should concentrate on in vitro and in vivo biological studies and structure activity relationship of various C21 steroid constituents.


Review of the studies on nutrition in Polish preschool children. Part 2. Meals prepared at preschool
This article is the second part of the review of the studies on nutrition in Polish preschool children. In the first part, studies on preschool menus assessment were presented and summarised, whereas this article reviews the studies on the assessment of foods and meals prepared at preschool. The aim of this review was to present and summarise the results of the studies on the assessment of meals prepared for children at preschool based on the reports from the preschool food storeroom, the studies on chemical analysis of sample meals served at preschools and the studies on comparison of the results of chemical analysis to the results obtained by calculations obtained from computer programmes. The results of the studies on the assessment of meals prepared for children at preschool using various methods confirm most of the findings from the studies on the assessment of preschool menus. It is necessary to carry out more studies on energy and nutrient content assessment of preschool meals determined by chemical analysis of sample meals in order to provide more accurate information about the real nutritional value of meals served to children at preschool. It is essential to update the Polish food composition tables to enable more precise calculations of nutritional value of the meals planned for children at preschools which will improve the possibility of adjusting preschool meals to the real needs of both 3-year-old and 4-6-year-old children during their stay at preschool.


Highly chemo- and enantioselective synthesis of 3-allyl-3-aryl oxindoles via the direct palladium-catalyzed alpha-arylation of amides.
A new NHC x Pd-catalyzed asymmetric alpha-arylation of amides is reported that gives direct access to synthetically valuable, allylated oxindoles with quaternary carbon centers. The reaction is made possible by the introduction of a new chiral NHC ligand. The palladium complexes derived therefrom combine excellent reactivity with high chemo- and enantioselectivity for the title transformation.


Binaural unmasking of frequency-following responses in rat amygdala.
Survival in natural environments for small animals such as rats often depends on precise neural coding of life-threatening acoustic signals, and binaural unmasking of species-specific pain calls is especially critical. This study investigated how species-specific tail-pain chatter is represented in the rat amygdala, which receives afferents from both auditory thalamus and auditory association cortex, and whether the amygdaloid representation of the chatter can be binaurally unmasked. The results show that chatter with a fundamental frequency (F0) of 2.1 kHz was able to elicit salient phase-locked frequency-following responses (FFRs) in the lateral amygdala nucleus in anesthetized rats. FFRs to the F0 of binaurally presented chatter were sensitive to the interaural time difference (ITD), with the preference of ipsilateral-ear leading, as well as showing features of binaural inhibition. When interaurally correlated masking noises were added and ipsilateral chatter led contralateral chatter, introducing an ITD disparity between the chatter and masker significantly enhanced (unmasked) the FFRs. This binaural unmasking was further enhanced by chemically blocking excitatory glutamate receptors in the auditory association cortex. When the chatter was replaced by a harmonic tone complex with an F0 of 0.7 kHz, both the binaural-inhibition feature and the binaural unmasking were preserved only for the harmonic of 2.1 kHz but not the tone F0. These results suggest that both frequency-dependent ascending binaural modulations and cortical descending modulations of the precise auditory coding of the chatter in the amygdala are critical for processing life-threatening acoustic signals in noisy and even reverberant environments.


Urine-Derived Induced Pluripotent Stem Cells in Cardiovascular Disease.
Recent studies have demonstrated that stem cells are equipped with the potential to differentiate into various types of cells, including cardiomyocytes. Meanwhile, stem cells are highly promising in curing cardiovascular diseases. However, owing to the ethical challenges posed in stem cell acquisition and the complexity and invasive nature of the method, large-scale expansions and clinical applications in the laboratory have been limited. The current generation of cardiomyocytes is available from diverse sources; urine is one of the promising sources among them. Although advanced research was established in the generation of human urine cells as cardiomyocytes, the reprogramming of urine cells to cardiomyocytes remains unclear. In this context, it is necessary to develop a minimally invasive method to create induced pluripotent stem cells (iPSCs). This review focuses on the latest advances in research on urine-derived iPSCs and their application mechanisms in cardiovascular diseases.


Genetic Diversity of Salt Tolerance in Miscanthus.
Miscanthus is a woody rhizomatous C4 grass that can be used as a CO2 neutral biofuel resource. It has potential to grow in marginal areas such as saline soils, avoiding competition for arable lands with food crops. This study explored genetic diversity for salt tolerance in Miscanthus and discovered mechanisms and traits that can be used to improve the yield under salt stress. Seventy genotypes of Miscanthus (including 57 M. sinensis, 5 M. sacchariflorus, and 8 hybrids) were evaluated for salt tolerance under saline (150 mM NaCl) and normal growing conditions using a hydroponic system. Analyses of shoot growth traits and ion concentrations revealed the existence of large variation for salt tolerance in the genotypes. We identified genotypes with potential for high biomass production both under control and saline conditions that may be utilized for growth under marginal, saline conditions. Several relatively salt tolerant genotypes had clearly lower Na+ concentrations and showed relatively high K+/Na+ ratios in the shoots under salt stress, indicating that a Na+ exclusion mechanism was utilized to prevent Na+ accumulation in the leaves. Other genotypes showed limited reduction in leaf expansion and growth rate under saline conditions, which may be indicative of osmotic stress tolerance. The genotypes demonstrating potentially different salt tolerance mechanisms can serve as starting material for breeding programs aimed at improving salinity tolerance of Miscanthus.


A Comparison of Deep Sclerectomy Trainer Versus Trainee Outcomes.
The aim of this study was to compare the results of deep sclerectomy (DS) and combined deep sclerectomy with phacoemulsification (phaco-DS) performed by clinical fellows with those by an experienced glaucoma surgeon and DS trainer. This is a retrospective nonrandomized study of 266 eyes of 226 consecutive patients who had DS or phaco-DS between March 2014 and December 2016 which were included from a database of all glaucoma surgery performed in our department. A minimum of 9 months follow-up was required. The cases were recorded as to whether a fellow or consultant performed the entire procedure. Overall, 114 surgeries were performed by the consultant and 164 surgeries were performed by the fellow, in which 91 cases received no assistance from the consultant. Intraocular pressure (IOP) success criteria were: (A) IOP<22 mm Hg and/or 20% decrease from baseline off any glaucoma medications and (B) IOP<16 mm Hg and/or 30% drop from baseline off any glaucoma medications. No statistically significant difference was noted by any criteria (P<0.05) between the 2 groups. The Kaplan-Meir IOP success rates at 2 years with criteria B (IOP<16 mm Hg without medications) were 64% for consultant, 76% for independent surgeries done by a fellow and 72% for surgeries with assistance from the consultant trainer (P=0.15). There were no significant differences between measured IOPs at any time after surgery. Intraoperative perforation of trabeculo-Descemet membrane was noted in 4 cases (3.5%) done by the consultant and 12 cases (7.3%) performed by fellows (Fisher exact P=0.19). IOP outcomes of DS and phaco-DS were not adversely affected if fellows performed surgery, whether under supervision or independently.


Impact of Adrenocortical Insufficiency on Biochemical Parameters in Haemodynamically Stable Cirrhotic Patients with Ascites.
Cirrhosis has many complications regardless of the aetiology. Among them, adrenal insufficiency is recently identified entity. A prospective cohort study was done to evaluate the biochemical impact of adrenocortical insufficiency in haemodynamically stable, non-septic, cirrhotic patients with ascites and had been performed at the inpatient of GHPD department, BIRDEM, Dhaka from April 2011 to March 2012. A total of fifty three (53) patients fulfilling inclusion criteria were included in the study. Patients were divided into two groups: Group A (patients of normal adrenal function) and Group B (patients of insufficient adrenal function) and those were followed up for the next 6 months. In Group A, the total number of patients was 25(47%) and in Group B it was 28(53%). Between two groups, mean age difference and gender difference were not statistically significant. (p value was 0.278 and 0.933, respectively). At enrollment, there was significant lower mean Hb concentration in Group B (p=0.008). There was no significant difference of means of WBC count and platelet count between two groups (p value was 0.829 and 0.333, respectively). There were significant abnormalities in serum bilirubin, serum albumin, INR, SBP, HRS, Serum Na concentration, TCO2 concentration in Group B patients at follow up after 6 months. Adrenal insufficient decompensated cirrhotic patients have higher biochemical abnormalities, thus higher morbidities.


Transdiaphragmatic, esophageal and gastric pressures during maximal static inspiratory and expiratory efforts in young subjects: effects of maneuver and sex.
Esophageal (Pes), gastric (Pga) and transdiaphragmatic (Pdi) pressures were measured in 6 young healthy men and 6 women during maximal static inspiratory and expiratory efforts. Interindividual variations were large for all pressures, but the measurements were highly reproducible within each subject. During maximal inspiratory efforts without instruction as to the type of breathing, Pga was often around zero whereas during standardized maximal inspiratory efforts (i.e. with protruded abdomen), Pdi and Pga increased significantly and Pes tended to be less negative. Thus, maximal strength of the diaphragm is only measured during standardized efforts. During maximal expiratory efforts Pes and Pga tended to be larger during spontaneous than during standardized maneuvers (i.e. with retracted abdomen), and to increase with lung volume. The clinical information obtained from Pdi, Pes and Pga during maximal inspiratory and expiratory efforts is probably not more specific than that from transrespiratory pressures (i.e. measurements at the mouth), except for standardized inspiratory efforts which may allow differentiation of intercostal-accessory and diaphragm-abdominal dysfunction.


Activation of defense response in common bean against stem rot disease triggered by Trichoderma erinaceum and Trichoderma viride.
White mold and stem rot is a common disease of Phaseolus vulgaris caused by Sclerotinia sclerotiorum. Biological control is a promising alternative for the control of this disease. In the present study, two Trichoderma spp., T. erinaceum and T. viride, and the consortium of both were evaluated as biocontrol agents against sclerotinia stem rot disease. The results revealed that T. erinaceum (NAIMCC-F-02171) and T. viride (NAIMCC-F-02500) when applied alone, significantly suppressed the infection rate of S. sclerotiorum and increased the rate of survival of plants by 74.5%. On the contrary, the combination of both the Trichoderma spp. was found to be more effective in reducing stem rot by 57.2% and increasing the survival of plants by 87.5% when compared to the individual Trichoderma applications. Further, the exogenous supplementation of Trichoderma activated antioxidative machineries, such as peroxidase, polyphenol oxidase, superoxide dismutase, catalase, and ascorbic acid in the plant. Besides, hydrogen peroxide and superoxide-free radical accumulation were also found to be reduced when T. erinaceum and T. viride were used either individually or in combination under the pathogen-challenged condition. Additionally, the photopigments in the bioprimed plants were markedly increased. Moreover, the combined inoculation of the two isolates yielded the highest records of growth parameters (root weight, shoot length, and leaf weight) compared with individual inoculation. Therefore, based on the above results, it was concluded that the combination of T. erinaceum and T. viride can be effectively used as an alternative to control white mold and stem rot caused by S. sclerotiorum.


Studies on the mechanism of hemorrhage production by five proteolytic hemorrhagic toxins from Crotalus atrox venom.
The sites and relative rates of peptide bond hydrolysis of the oxidized B chain of bovine insulin by two hemorrhagic proteinases, Ht-a and Ht-b, isolated from the venom of the Western Diamondback Rattlesnake, Crotalus atrox, were investigated. The results were compared with previous results on the digestion of the same substrate by the C. atrox hemorrhagic proteinases Ht-c, d, and e. Both toxins, Ht-a and Ht-b, were found to cleave the His5-Leu6, His10-Leu11, Ala14-Leu15, and Tyr16-Leu17 bonds of the oxidized insulin B chain. In addition, Ht-a cleaves the Asn3-Gln4 bond, whereas Ht-b cleaves the Gly23-Phe24 bond. The cleavage specificity of Ht-b on the insulin B chain is identical to that of the weakly hemorrhagic isoenzymes Ht-c and Ht-d. Hemorrhagic proteinase Ht-a cleaves the Ala14-Leu15 bond most rapidly, having a turnover number of 12.6 min-1 which was approximately twice as fast as the Tyr16-Leu17 bond turnover of cleavage. Hemorrhagic proteinase Ht-b, on the other hand, cleaves the Tyr16-Leu17 bond fastest, having a turnover number of 61.3 min-1. The Ala14-Leu15 bond is the peptide bond cleaved the second fastest by Ht-b, with a turnover number of 48.2 min-1. The five hemorrhagic toxins from Crotalus atrox venom were also examined for their capability to hydrolyse basement membrane preparations, and the identities of the digested proteins comprising the basement membrane were determined. From the results it is concluded that all five hemorrhagic toxins cleave laminin and the component of the basement membrane referred to as band a.(ABSTRACT TRUNCATED AT 250 WORDS)


A multicenter, randomized, double-blind, placebo-controlled, dose-finding trial of a long-acting formulation of octreotide in promoting weight loss in obese adults with insulin hypersecretion.
To compare changes in weight in obese patients who received long-acting octreotide (octreotide LAR) at one of three dose levels (20, 40, or 60 mg) or placebo over 6 months and to identify the lowest dose of octreotide LAR that safely achieved optimal weight loss. Randomized, double-blind, placebo-controlled trial of octreotide LAR at three dose levels. A total of 172 adults (28 men and 144 women) with at least moderate obesity (body mass index (BMI) range 30-65 kg/m2) and evidence of insulin hypersecretion were enrolled. Patients were predominantly either Caucasian (50.0%) or African American (45.3%). The mean age (38 +/- 11 year), weight (110.7 +/- 23 kg), and BMI (39.8 +/- 6.5 kg/m2) were similar across the four treatment groups. Efficacy measures included weight, BMI, fasting serum glucose; triglycerides; percentage of total body fat and abdominal fat as measured by dual-energy X-ray absorptiometry; skin fold thickness; waist-to-hip circumference; leptin; percentage of carbohydrates, fat, and protein ingested; nutritional evaluation (including dietary analysis--3-day food record); quality of life (QoL; using the Impact of Weight on Quality of Life-Lite); Beck Depression Inventory; and Carbohydrate Craving Questionnaire. Safety measures included medical history, vital signs, physical examinations, hematology, blood chemistries, thyroid function tests, hemoglobin A1c, gallbladder ultrasound, electrocardiograms, and adverse events. After 6 months of treatment, patients receiving 40 or 60 mg of octreotide LAR experienced statistically significant weight loss compared to baseline, with mean differences from placebo in percent weight change of -1.98 and -1.87%, respectively. This finding was accompanied by statistically significant mean decreases in BMI compared to baseline, that is, a mean decrease of 0.73 and 0.79 kg/m2 for the 40 and 60 mg treatment arms, respectively. The observed weight loss was progressive during the 6-month treatment in the two higher dose groups. The lowest dose to reach statistical significance in weight loss after 6 months' treatment was 40 mg. Post hoc analysis revealed a 3.5-3.8% weight loss at month 6 in the two higher dose groups among Caucasian patients having insulin secretion greater than the median of the cohort, defined as CIR(gp) (corrected insulin response at the glucose peak) > or = 1.43. There were no statistically significant changes in QoL scores, body fat, leptin concentration, Beck Depression Inventory, or macronutrient intake. Mean changes of blood glucose AUC(0-180 min) during an oral glucose tolerance test in patients taking octreotide LAR were 39-40 mg/dl h higher than those on placebo. A total of 7-21% of the patients taking octreotide LAR reached a 5% or greater decrease in body weight from Baseline, compared to 11% for the placebo group. This was not statistically significant. The most common adverse events included diarrhea, headache, cholelithiasis, nausea, and abdominal pain. Octreotide LAR given at 40 or 60 mg resulted in statistically significant weight loss. A post hoc analysis stratifying patients by race and CIR(gp) indicated that Caucasian patients with the greater degree of insulin hypersecretion appeared to derive the most benefit from treatment. The observed safety profile was consistent with the known effects of octreotide from previous studies.


Transient response of encapsulated enzymes in hollow-fiber reactor.
A mathematical model for the transient response of encapsulated enzymes is developed showing the effects of the outer boundary layer, the encapsulating membrane, the partition coefficient, and diffusion with reaction within the encapsulating medium. The model incorporates both first-order kinetics and Michaelis-Menten kinetics for the reaction rate. Using typical hollow-fiber or microcapsule parameters, the model shows that (a) the partition coefficient affects the overall rate only when the rate-limiting step is diffusion through the membrane, (b) the transient overall effectiveness factor rises sharply with time and approaches an asymptotic value for most situations, and (c) the first-order approximation to Michaelis-Menten kinetics is not valid when the initial outside bulk concentration is higher than the Michaelis constant and the overall rate is reaction limited. The model is compared with experimental data using uricase in a hollow-fiber enzyme reactor configuration. Batch assay and CSTUER (continuous-stirred ultrafiltration enzyme reactor) studies were conducted on the free enzyme to provide some of the parameters used in the model. The CSTUER data fit the case of substrate inhibition kinetics with the apparent Michaelis constant approaching zero. The hollow-fiber reactor was conducted with uricase dissolved in both a buffer solution and a concentrated hemoglobin solution. Diffusivities of the solute were measured in both solutions as was the osmotic pressure of the hemoglobin solution. While experimental data for uricase in buffer solution could easily be matched by the model, that in the concentrated hemoglobin solution could not.


Apple-marigold intercropping improves soil properties by changing soil metabolomics and bacterial community structures.
Marigold can protect crops against soil-borne diseases. However, the effects of intercropping with marigold on apple rhizosphere soils are not known. In this study, we investigated the metabolite profiles and bacterial community structures in rhizosphere soils of the apple-marigold intercropping system by high-throughput sequencing and soil metabolomics. The results show that intercropping marigold could significantly enhance soil moisture, nitrogen, and enzyme activities compared with clean tillage. The soil metabolite profiles and the soil bacterial community structures in the rhizosphere soils were different between the inter-and mono-cropping systems. Among nine metabolites, carbohydrates were more increased in the intercropping system than in the monocropping system. Pathway enrichment analysis revealed that the greatest differential, in terms of metabolic pathway, was starch and sucrose metabolism. Moreover, intercropping marigold significantly increased the relative abundance of plant growth promoting bacteria in rhizosphere soils, such as Rhizobiales, Pseudomonadales, and Bacillales. These results indicate that marigold intercropping positively affected the apple orchard's soil quality and may provide a new intercropping technique to improve soil fertility in orchards and promote plant growth.


Prostate cancer gene therapy-what have we learned and where are we going?
With recent advances in genetic engineering, tumor biology, and immunology, gene therapy has been recognized as a promising new treatment option for various cancers, including prostate cancer. Several clinical trials of prostate cancer gene therapy, using therapeutic genes which include suicide genes, immunomodulatory genes, tumor suppressor genes, and anti-oncogenes, are under way and preliminary reports have emerged. Although gene therapy for prostate cancer is still at an early stage and requires additional technological breakthroughs, new insights obtained from recent clinical trials indicate a promising potential for prostate cancer gene therapy. In this report, general concepts, current progress, and future prospects in prostate cancer gene therapy are summarized.


Synthetic DNA Delivery of an Optimized and Engineered Monoclonal Antibody Provides Rapid and Prolonged Protection against Experimental Gonococcal Infection.
Monoclonal antibody (MAb) 2C7 recognizes a lipooligosaccharide epitope expressed by most clinical Neisseria gonorrhoeae isolates and mediates complement-dependent bactericidal activity. We recently showed that a recombinant human IgG1 chimeric variant of MAb 2C7 containing an E430G Fc modification (2C7_E430G), which enhances complement activation, outperformed the parental MAb 2C7 (2C7_WT) in vivo Because natural infection with N. gonorrhoeae often does not elicit protective immunity and reinfections are common, approaches that prolong bacterial control in vivo are of great interest. Advances in DNA-based approaches have demonstrated the combined benefit of genetic engineering, formulation optimizations, and facilitated delivery via CELLECTRA-EP technology, which can induce robust in vivo expression of protective DNA-encoded monoclonal antibodies (DMAbs) with durable serum activity relative to traditional recombinant MAb therapies. Here, we created optimized 2C7-derived DMAbs encoding the parental Fc (2C7_WT) or complement-enhancing Fc variants (2C7_E430G and 2C7_E345K). 2C7 DMAbs were rapidly generated and detected throughout the 4-month study. While all complement-engaging 2C7 variants facilitated rapid clearance following primary N. gonorrhoeae challenge (day 8 after DMAb administration), the complement-enhancing 2C7_E430G variant demonstrated significantly higher potency against mice rechallenged 65 days after DMAb administration. Passive intravenous transfer of in vivo-produced, purified 2C7 DMAbs confirmed the increased potency of the complement-enhancing variants. This study highlights the ability of the DMAb platform to launch the in vivo production of antibodies engineered to promote and optimize downstream innate effector mechanisms such as complement-mediated killing, leading to hastened bacterial elimination.IMPORTANCENeisseria gonorrhoeae has become resistant to most antibiotics in clinical use. Currently, there is no safe and effective vaccine against gonorrhea. Measures to prevent the spread of gonorrhea are a global health priority. A monoclonal antibody (MAb) called 2C7, directed against a lipooligosaccharide glycan epitope expressed by most clinical isolates, displays complement-dependent bactericidal activity and hastens clearance of gonococcal vaginal colonization in mice. Fc mutations in a human IgG1 chimeric version of MAb 2C7 further enhance complement activation, and the resulting MAb displays greater activity than wild-type MAb 2C7 in vivo Here, we utilized a DNA-encoded MAb (DMAb) construct designed to launch production and assembly of "complement-enhanced" chimeric MAb 2C7 in vivo The ensuing rapid and sustained MAb 2C7 expression attenuated gonococcal colonization in mice at 8 days as well as 65 days postadministration. The DMAb system may provide an effective, economical platform to deliver MAbs for durable protection against gonorrhea.


Camel racing injuries among children.
The aim of this study is to determine the frequency and severity of camel racing injuries among children aged 5 to 15 years during the period 1992 to 2003 in the State of Qatar. Case series. The study was conducted in the Hamad General Hospital, State of Qatar, from January 1992 to December 2003. A total of 275 subjects aged 5 to 15 years with camel racing injuries who were seen at the Accident Emergency Department, Critical Care, and Physiotherapy Departments of the Hamad General Hospital were studied. The sociodemographic information and the details of the injury of the studied subjects were collected. The Abbreviated Injury Scale system was used to determine the severity of injury. Overall, 275 camel racing injuries were reported among boys aged 5 to 15 years. The majority of patients were Sudanese (91.3%). The most commonly injured locations were upper limb (23.2%), lower limb (21.1%), and head (20.7%), followed by other injury locations. Seventeen patients were disabled as a result of their injury, and another 3 injuries were fatal. This study revealed that 34% of injuries were considered to be minor, 22.1% moderate, 18.1% serious, 11.6% critical, and 6.4% maximum. The injury severity caused by the camel racing significantly affected the length of hospital stay. At present, the government is serious about this problem, and there is a draft of proposed legislation intended to prevent the employment of children below the age of 12 as camel jockeys.


Intravenous Tomato Lectin Injection to Assess Functional Vasculature.
Pluripotent stem cells have recently allowed for the development of tissue models for the various organ systems within the body. These models allow scientists to study organ function, physiology, embryology, and even pathologic processes. Studies on tissue can be done in vitro and/or transplanted into animal models for studies in vivo. Recently, our lab developed a model of human small intestine derived from human pluripotent stem cells which when transplanted in vivo, matured into an intestinal structure similar to that of adult intestine. The maturity of the transplanted human intestinal tissue was dependent upon the development of an adequate blood supply primarily from the murine host. In order to better study the developed vascular network within our transplanted intestinal tissue, we injected Fluorescein labeled Lycopersicon esculentum (tomato) lectin into the mouse tail vein (Watson et al., 2014). Using the property of this lectin to bind to the endothelium, we were able to visualize the vasculature within the transplant.


Vascular Augmentation in Renal Transplantation: Supercharging and Turbocharging.
The most common anatomic variant seen in donor kidneys for renal transplantation is the presence of multiple renal arteries, which can cause an increased risk of complications. Accessory renal arteries should be anastomosed to the proper source arteries to improve renal perfusion via the appropriate vascular reconstruction techniques. In microsurgery, 2 kinds of vascular augmentation methods, known as 'supercharging' and 'turbocharging,' have been introduced to ensure vascular perfusion in the transferred flap. Supercharging uses a distant source of the vessels, while turbocharging uses vascular sources within the same flap territory. These technical concepts can also be applied in renal transplantation, and in this report, we describe 2 patients who underwent procedures using supercharging and turbocharging. In one case, the ipsilateral deep inferior epigastric artery was transposed to the accessory renal artery (supercharging), and in the other case, the accessory renal artery was anastomosed to the corresponding main renal artery with a vascular graft (turbocharging). The transplanted kidneys showed good perfusion and proper function. No cases of renal failure, hypertension, rejection, or urologic complications were observed. These microsurgical techniques can be safely utilized for renal transplantation with donor kidneys that have multiple arteries with a lower complication rate and better outcome.


Experiencing food insecurity in childhood: influences on eating habits and body weight in young adulthood.
To examine how food insecurity in childhood up to adolescence relates to eating habits and weight status in young adulthood. A longitudinal study design was used to derive trajectories of household food insecurity from age 4·5 to 13 years. Multivariable linear and logistical regression analyses were performed to model associations between being at high risk of food insecurity from age 4·5 to 13 years and both dietary and weight outcomes at age 22 years. A birth cohort study conducted in the Province of Quebec, Canada. In total, 698 young adults participating in the Québec Longitudinal Study of Child Development. After adjusting for sex, maternal education and immigrant status, household income and type of family, being at high risk (compared with low risk) of food insecurity in childhood up to adolescence was associated with consuming higher quantities of sugar-sweetened beverages (ßadj: 0·64; 95 % CI (0·27, 1·00)), non-whole-grain cereal products (ßadj: 0·32; 95 % CI (0·07, 0·56)) and processed meat (ßadj: 0·14; 95 % CI (0·02, 0·25)), with skipping breakfast (ORadj: 1·97; 95 % CI (1·08, 3·53)), with eating meals prepared out of home (ORadj: 3·38; 95 % CI (1·52, 9·02)), with experiencing food insecurity (ORadj: 3·03; 95 % CI (1·91, 4·76)) and with being obese (ORadj: 2·01; 95 % CI (1·12, 3·64)), once reaching young adulthood. Growing up in families experiencing food insecurity may negatively influence eating habits and weight status later in life. Our findings reinforce the importance of public health policies and programmes tackling poverty and food insecurity, particularly for families with young children.


A quality management approach to controlled ovarian stimulation in assisted reproductive technology: the "Fischer protocol".
Ovarian stimulation (OS) is crucial for pregnancy success in assisted reproductive technology (ART) treatments. The possibility of programming the OS cycle and oocyte pick-up (OPU) is advantageous to Fertility Centers operating under quality management systems (QMS) as it might increase efficiency and safety. Moreover, cycle programming is patient-centered as it might help IVF patients to most optimally manage domestic and work commitments. In this study, we describe the so-called "Fischer protocol" to IVF cycle programming and present the clinical results of using this approach in two independent Fertility Centers certified according to DIN EN ISO 9001 standards. Cycle programming was achieved in normo-ovulatory women with pretreatment administration of norethisterone acetate, followed by OS using individualized doses of recombinant human FSH and recombinant human LH in a fixed 2:1 ratio in association with a flexible GnRH antagonist regimen. The final oocyte maturation was attained with use of GnRH agonist trigger. The oocyte pick-ups (OPU) were scheduled approximately 40 days ahead of the programed OPU date. The cycle outcomes of 647 patients treated using the "Fischer protocol" in the Center where the method was developed (study center 1) are presented. The model was then tested at an independent Fertility Center (study center 2), and the first clinical results using the Fischer protocol in 216 patients are presented and compared with that of 516 patients undergoing conventional OS without cycle programming. The duration of ovarian stimulation was 9±1 day in all treated patients. No OPU was scheduled during weekends or had to be re-scheduled due to issues related to cycle programming. In the study center 1, the highest and lowest mean number of oocytes retrieved was 11.7 (95% confidence interval [CI]: 4.5-22.1) in patients of ≤30 years and 7.7 (95% CI: 1-19) in those aged 40 years and over. No cases of OHSS were recorded in this series. The mean number of embryos transferred was 1.5 and the overall clinical pregnancy rates (CPR) and live birth rates (LBR) were 52.7% and 43.5%, respectively. In the study center 2, patients treated using the Fisher protocol achieved statistically higher oocyte output rate (94.6% vs. 85.0%), number of oocytes retrieved (9.8±7.7 vs. 7.9±7.2), and blastulation rates (55.1% vs. 49.4%) than those treated using conventional OS. The CPR (50.6% vs. 41.1%) and LBR (44.7% vs. 33.2%) also favored the group of patients subjected to cycle programming using the Fisher protocol, although this data mainly resulted from the increased frequency of patients subjected to preimplantation genetic testing for aneuploidy (PGT-A). An optimal distribution of both clinical and laboratory workload was achieved by using the Fischer protocol. Moreover, oocyte pick-ups were eliminated on weekends and holidays without jeopardizing the quality of care provided to couples. The Fischer protocol is consistent with the quality management philosophy and focusses on improving the quality of care by increasing safety, efficacy, and patient-centeredness without harming treatment effectiveness.


Antithrombogenicity of hydrophilic polyurethane-hydrophobic polystyrene IPNs. I. Synthesis and characterization.
A series of interpenetrating polymer networks (IPNs) composed of hydrophilic polyurethane (PU) and hydrophobic polystyrene (PS) were prepared by the simultaneous polymerization method. The PU network was synthesized via the isocyanate-terminated PU prepolymer based on polyethylene glycol (PEG), a highly hydrophilic oligomer, and hexamethylene diisocyanate (HDI). The bulk and surface characteristics of these materials were analyzed by differential scanning calorimetry (DSC), tensile testing, scanning electron microscopy (SEM), attenuated total reflectance-Fourier transform infrared (ATR-FTIR), electron spectroscopy for chemical analysis (ESCA), and contact angle measurement. The PU/PS IPNs prepared in this study exhibited phase separated structures, which had dispersed PS domains in the continuous PU matrix, in both the bulk and surface showing two transition temperatures. The IPN containing 50 wt% of PS showed good mechanical properties. The enrichment of PU phase in the surface was revealed by SEM, ATR-FTIR, ESCA, and contact angle measurement.


Retirement and mental health.
This research examines whether retirement is associated with mental health and how one's daily pursuits mediate this association. It tests two perspectives from the sociology of work and the sociology of mental health. Using data from two surveys, the 1995 Aging, Status, and Sense of Control and the 1987-1988 National Survey of Families and Households, regression analysis was used to examine retirement, activities, and well-being. In support of the view that work is alienating and retirement liberating, retirees experienced less anxiety and distress and higher positive affect. Retirees' lower anxiety and distress were explained by activity characteristics. In support of the view that work is empowering and retirement demoralizing, retirement is associated with lower sense of control in both data sets, in part because of the daily pursuits. Retirement was not associated with depressive symptomatology. Suggestions for creating opportunities that enhance well-being are discussed.


[Osteoporosis and fractures: a review of current therapies].
The authors examine the effects of different drugs used in osteoporosis therapy for the primary and secondary prevention of fractures. They base their review on prospective randomized studies; retrospective studies are included only if a consistent number of subjects has been examined. Their methodological characteristics are illustrated, and results with significant levels and 95% confidence intervals are reported. Only hormone replacement therapy and salmon calcitonin have been demonstrated as able to prevent vertebral and non-vertebral fractures. Vitamin D and its analogues seem to be effective only in elderly patients, although conclusive data are lacking. With regard to bisphosphonates, only data on vertebral fractures are presently available. Results from fluoride studies are still very inconclusive, and, in fact, lead to the hypothesis of a fracture-promoting effect. At present, no data on ipriflavone are available. Considerably more research is necessary to define the efficacy of different treatment protocols for fracture prevention. Each therapeutic proposal for osteoporosis should be supported by data on its efficacy in reducing the incidence of fractures. Not always, in fact, is an absolute increase of bone mass followed by the effective prevention of fractures. At this time, only estrogens and calcitonin have been demonstrated as able to reduce fracture incidence.


Peer review for social accountability of health sciences education: a model from South Africa.
The Collaboration for Health Equity in Education and Research (CHEER) is unique in the composition of its members who represent all the Faculties of Health Sciences in South Africa. Over the past 10 years, CHEER has conducted 18 peer reviews involving all the institutions. In August 2012, CHEER embarked on its pilot peer review on Social Accountability in Health Sciences in South Africa. This paper shares the lessons learned and insights from the pilot process. A descriptive study design, using qualitative methods, which focused primarily on semi-structured interviews and focus group discussions, supplemented with supporting documentation, was employed. The protocol was developed by CHEER members and ethics approval was obtained. Arising from our pilot peer review, reviewers identified several key components of the review process that should be noted for future reviews on social accountability. These relate to: (a) The composition of the review team; (b) the review process; (c) data collection and analysis; and (d) the reporting process. Peer review is a useful way of building consensus and a common set of values that become more explicit through the process. We found that six criteria, namely, values, reference population, partnerships, student profile, graduate outcomes and impact, provide the basis for establishing standards for reflecting social accountability. The peer review is a process of institutional self-review supported by 'a panel of critical friends' and is useful when considered as part of the process of preparation for the formal accreditation review at Health Sciences educational institutions.


Ethanol combined with energy drinks: Two decades of research in rodents.
Many studies raised concerns on alcoholic beverages consumption mixed with energy drinks (AmED), which can induce higher rates of binge drinking and earlier development of alcohol use disorders. After 20 years of research, few studies with laboratory animals have focused on the effects of this mixture and the neurobiological and pharmacological mechanisms underlying them. We found 16 articles on AmED administration to rodents evaluating its effects on voluntary consumption, locomotion, anxiety-like behavior, memory, influence on the onset time of seizures, biochemical and neurochemical measures. Some of these studies indicated energy drinks (ED) can alter the pattern of use and motivation to consume ethanol (EtOH); increase the expression of sensitization to EtOH stimulant effect and the proportion of sensitized mice; decrease the aversiveness of high concentrations of EtOH, among other effects. In addition AmED hastens the loss of righting reflex and its effects on memory are controversial. After acute administration no difference was found in blood ethanol concentration (BEC) of rodents which received EtOH with or without ED, but after 60 days of treatment, AmED group had lower BEC levels than EtOH group. Data on biochemical and neurochemical parameters after AmED are not consistent. Although the AmED group presented higher glucose levels than the EtOH group when drugs were administered by gavage, this was not observed in a self-administration protocol. AmED may induce higher kidney damage, higher levels of plasma urea, uric acid and creatinine when compared to EtOH. Chronic consumption of AmED causes an inflammatory response and oxidative stress, which may induce cell death in the cortex and hypothalamus of adult rats. These controversial results show that AmED diverse effects depend on sex, age and lineage of the animals, duration of the treatment and route of administration. Further research is necessary to evaluate the mechanisms underlying AmED biological effects.


The New Standard Is Biodigital: Durable and Elastic 3D-Printed Biodigital Clay Bricks.
In a previously published study, the authors explained the formal design efficiency of the 3D-printed biodigital clay bricks 3DPBDCB: a project that aimed to change the conventional methods of clay brick design and mass production. This was achieved by employing the behavioural algorithms of reaction-diffusion and the shortest path that were extracted from the exact material physical properties and hydrophilic behaviours of clay and controlled material deposition 3D printing to create sustainable clay bricks. Sustainability in their use in the built environment and their production processes, with full potential sustainability aspects such as passive cooling, thermal and acoustical insulation, and bio receptivity. The current work studies the mechanical properties of the 3D-printed biodigital clay bricks as elastic and durable clay bricks whose properties depend mainly on their geometrical composition and form. Each of the three families of the 3D-printed biodigital clay bricks (V1, V2, V3) includes the linear model of a double line of 0.5 cm thickness and a bulk model of 55% density were tested for compression and elasticity and compared to models of standard industrial clay bricks. The results revealed that the best elasticity pre-cracking was achieved by the V2 linear model, followed by the V3 linear model, which also achieved the highest post-cracking elasticity-enduring until 150 N pre-cracking and 200 N post-cracking, which makes the V3 linear model eligible for potential application in earthquake-resistant buildings. While the same model V3-linear achieved the second-best compressive strength enduring until 170 N. The best compressive strength was recorded by the V1 linear and bulk model enduring up to 240 N without collapsing, exceeding the strength and resistance of the industrial clay bricks with both models, where the bulk and the perforated collapsed at 200 N and 140 N, respectively. Thus, the mass production and integration of the V1 bulk and linear model and the V3 linear model are recommended for the construction industry and the architectural built environment for their multi-aspect sustainability and enhanced mechanical properties.


Interim final rules under the Paul Wellstone and Pete Domenici Mental Health Parity and Addiction Equity Act of 2008. Interim final rules with request for comments.
This document contains interim final rules implementing the Paul Wellstone and Pete Domenici Mental Health Parity and Addiction Equity Act of 2008, which requires parity between mental health or substance use disorder benefits and medical/surgical benefits with respect to financial requirements and treatment limitations under group health plans and health insurance coverage offered in connection with a group health plan.


Using hierarchical clustering and dendrograms to quantify the clustering of membrane proteins.
Cell biologists have developed methods to label membrane proteins with gold nanoparticles and then extract spatial point patterns of the gold particles from transmission electron microscopy images using image processing software. Previously, the resulting patterns were analyzed using the Hopkins statistic, which distinguishes nonclustered from modestly and highly clustered distributions, but is not designed to quantify the number or sizes of the clusters. Clusters were defined by the partitional clustering approach which required the choice of a distance. Two points from a pattern were put in the same cluster if they were closer than this distance. In this study, we present a new methodology based on hierarchical clustering to quantify clustering. An intrinsic distance is computed, which is the distance that produces the maximum number of clusters in the biological data, eliminating the need to choose a distance. To quantify the extent of clustering, we compare the clustering distance between the experimental data being analyzed with that from simulated random data. Results are then expressed as a dimensionless number, the clustering ratio that facilitates the comparison of clustering between experiments. Replacing the chosen cluster distance by the intrinsic clustering distance emphasizes densely packed clusters that are likely more important to downstream signaling events.We test our new clustering analysis approach against electron microscopy images from an experiment in which mast cells were exposed for 1 or 2 minutes to increasing concentrations of antigen that crosslink IgE bound to its high affinity receptor, FcϵRI, then fixed and the FcϵRI β subunit labeled with 5 nm gold particles. The clustering ratio analysis confirms the increase in clustering with increasing antigen dose predicted from visual analysis and from the Hopkins statistic. Access to a robust and sensitive tool to both observe and quantify clustering is a key step toward understanding the detailed fine scale structure of the membrane, and ultimately to determining the role of spatial organization in the regulation of transmembrane signaling.


Ovarian ultrasonography in the mare.
Ultrasonography has become indispensable in the control of equine reproduction. Mare ovary layers are inverted with respect to other species, with the follicles and corpus luteum found inside the ovary; only large follicles protrude from the organ's surface. This renders the making of diagnoses via rectal palpation of the ovaries very difficult. Ultrasound imaging, however, provides another avenue of examination. Since its first use in 1980, the diagnostic potential of ultrasonography has greatly improved. Colour Doppler ultrasonography can even asses blood flow, allowing for much better monitoring of ovarian activity. This study discusses the use of ultrasound, and in particular colour Doppler ultrasonography, in the monitoring of mare ovarian function and disease.