The effects of hydration on core temperature in pediatric surgical patients.
Reduced vascular volume might influence body temperature by diverting heat flow from peripheral tissues to the central organs. We therefore tested the hypothesis that mild hypovolemia helps to prevent intraoperative hypothermia in pediatric patients. Twenty-two pediatric patients (aged 1-3 yr) undergoing prolonged minor surgery were randomly assigned to conservative (n = 12) or aggressive (n = 10) perioperative fluid management. The conservative group fasted 8 h before surgery and received a crystalloid at 1 ml. kg-1. h-1 during surgery. The aggressive group was allowed to drink liquids until 3 h before surgery and was given a maintenance crystalloid at 8 ml. kg-1. h-1. Anesthesia was induced and maintained with halothane in nitrous oxide. Ambient temperature was kept near 25 degrees C, but the patients were not actively warmed. During recovery from anesthesia, additional fluid was given to the conservative group so that perioperative fluid totaled 9.5 ml. kg-1. h-1 in both groups. Intraoperative body weight remained unchanged in the aggressive group and decreased only 1% in patients managed conservatively. Heart rate was slightly greater in the conservative group (107 +/- 9 vs. 95 +/- 4 beats/min, P = 0.002), but blood pressure was similar. Esophageal temperature in patients whose fluid was managed conservatively increased significantly, by 0.4 +/- 0.3 degrees C, to 37.1 degrees C; in contrast, temperature in the aggressive group decreased significantly, by 0.4 +/- 0.2 degrees C, to 36.4 degrees C (P < 0.001 between groups). Temperatures remained significantly different 1 h after surgery. Conservative fluid management, which decreased body weight by only 1%, prevented reduction in core body temperature, presumably by reducing dissipation of metabolic heat from the core thermal compartment to peripheral tissues.


Expression of purinergic receptors in non-melanoma skin cancers and their functional roles in A431 cells.
We investigated the use of purinergic receptors as a new treatment modality for nonmelanoma skin cancers. Purinergic receptors, which bind adenosine 5'-tri-phosphate, are expressed on human cutaneous keratinocytes. Previous work in rat and human epidermis suggested functional roles for purinergic receptors in the regulation of proliferation, differentiation, and apoptosis. Immunohistochemical analysis of frozen sections in human basal cell carcinomas and squamous cell carcinomas for P2X5, P2X7, P2Y1, P2Y2, and P2Y4 receptors was performed, accompanied by detailed analysis of archive material of tumor subtypes in paraffin sections. Functional studies were performed using a human cutaneous squamous cell carcinoma cell line (A431), where purinergic receptor subtype agonists were applied to cells and changes in cell number were quantified via a colorimetric assay. Immunostaining in paraffin sections was essentially the same as that in frozen sections, although more detail of the subcellular composition was visible. P2X5 and P2Y2 receptors were heavily expressed in basal cell carcinomas and squamous cell carcinomas. P2X7 receptors were expressed in the necrotic center of nodular basal cell carcinomas and in apoptotic cells in superficial multifocal and infiltrative basal cell carcinomas, and squamous cell carcinomas. P2Y1 receptors were only expressed in the stroma surrounding tumors. P2Y4 receptors were found in basal cell carcinomas but not in squamous cell carcinomas. P2X5 receptors appear to be associated with differentiation. The P2X7 receptor agonist benzoylbenzoyl-adenosine 5'-triphosphate and high concentrations of adenosine 5'-triphosphate (1000-5000 microM) caused a significant reduction in A431 cell number (p<0.001), whereas the P2Y2 receptor agonist uridine 5'-triphosphate caused a significant amount of proliferation (p<0.001). We have demonstrated that non-melanoma skin cancers express functional purinergic receptors and that P2X7 receptor agonists significantly reduce cell numbers in vitro.


Alternative donor transplantation after reduced intensity conditioning: results of parallel phase 2 trials using partially HLA-mismatched related bone marrow or unrelated double umbilical cord blood grafts.
The Blood and Marrow Transplant Clinical Trials Network conducted 2 parallel multicenter phase 2 trials for individuals with leukemia or lymphoma and no suitable related donor. Reduced intensity conditioning (RIC) was used with either unrelated double umbilical cord blood (dUCB) or HLA-haploidentical related donor bone marrow (Haplo-marrow) transplantation. For both trials, the transplantation conditioning regimen incorporated cyclophosphamide, fludarabine, and 200 cGy of total body irradiation. The 1-year probabilities of overall and progression-free survival were 54% and 46%, respectively, after dUCB transplantation (n = 50) and 62% and 48%, respectively, after Haplo-marrow transplantation (n = 50). The day +56 cumulative incidence of neutrophil recovery was 94% after dUCB and 96% after Haplo-marrow transplantation. The 100-day cumulative incidence of grade II-IV acute GVHD was 40% after dUCB and 32% after Haplo-marrow transplantation. The 1-year cumulative incidences of nonrelapse mortality and relapse after dUCB transplantation were 24% and 31%, respectively, with corresponding results of 7% and 45%, respectively, after Haplo-marrow transplantation. These multicenter studies confirm the utility of dUCB and Haplo-marrow as alternative donor sources and set the stage for a multicenter randomized clinical trial to assess the relative efficacy of these 2 strategies. The trials are registered at www.clinicaltrials.gov under NCT00864227 (BMT CTN 0604) and NCT00849147 (BMT CTN 0603).


Systematic review comparing meropenem with imipenem plus cilastatin in the treatment of severe infections.
To compare the effectiveness of meropenem with imipenem plus cilastatin in the treatment of severe infections. CENTRAL, EMBASE and MEDLINE were searched for abstracts and papers. All searching was completed in March 2004. No restriction was placed on language. Randomized controlled trials of adult patients with severe infections treated with meropenem or imipenem plus cilastatin at an equal dose, on a gram-for-gram basis, and with the same dosing regimen. Two reviewers independently assessed papers against the inclusion/exclusion criteria and for methodological quality with differences in opinion adjudicated by a third party. Data were extracted on clinical response, bacteriologic response, mortality and adverse events. A total of 27 trials met the inclusion criteria. Meta-analyses were carried out using a Fixed Effects model. Results demonstrated that when compared to imipenem plus cilastatin, meropenem is associated with a significantly greater clinical response (Relative Risk 1.04; 95% Confidence Interval: 1.01-1.06), a significantly greater bacteriologic response (RR 1.05; 95% CI: 1.01-1.08), a non-significant reduction in mortality (RR 0.98; 95% CI: 0.71-1.35), and a significantly lower adverse event rate (RR 0.87; 95% CI: 0.77-0.97). This systematic review demonstrates that meropenem compared to imipenem plus cilastatin has a significantly greater clinical and bacteriologic response with a significant reduction in adverse events. There was no evidence of heterogeneity or publication bias and the analyses were robust to changes in the inclusion/exclusion criteria and use of a Random Effects model.


[The spectral characteristics of the electrical activity in the rabbit brain during the hunger dominant].
By means of daily alimentary deprivation the dominant of hunger was created in rabbits. In response to acoustic stimuli summational swallowing and chewing movements appeared. Spectral analysis of the electrical brain activity showed the presence of primary dominant focus zone (lateral and ventromedial hypothalamus), characterized by an increase of spectrum power in delta-range while in the orbito-frontal, sensorimotor, parietal cerebral cortex, in the medial and lateral preoptic hypothalamic zones the power of biopotentials spectrum decreased within the whole analyzed frequency range.


Retinoic Acid-Loaded Dendritic Polyglycerol-Conjugated Gold Nanostars for Targeted Photothermal Therapy in Breast Cancer Stem Cells.
The existence of cancer stem cells (CSCs) poses a major obstacle for the success of current cancer therapies, especially the fact that non-CSCs can spontaneously turn into CSCs, which lead to the failure of the treatment and tumor relapse. Therefore, it is very important to develop effective strategies for the eradication of the CSCs. In this work, we have developed a CSCs-specific targeted, retinoic acid (RA)-loaded gold nanostars-dendritic polyglycerol (GNSs-dPG) nanoplatform for the efficient eradication of CSCs. The nanocomposites possess good biocompatibility and exhibit effective CSCs-specific multivalent targeted capability due to hyaluronic acid (HA) decorated on the multiple attachment sites of the bioinert dendritic polyglycerol (dPG). With the help of CSCs differentiation induced by RA, the self-renewal of breast CSCs and tumor growth were suppressed by the high therapeutic efficacy of photothermal therapy (PTT) in a synergistic inhibitory manner. Moreover, the stemness gene expression and CSC-driven tumorsphere formation were significantly diminished. In addition, the in vivo tumor growth and CSCs were also effectively eliminated, which indicated superior anticancer activity, effective CSCs suppression, and prevention of relapse. Taken together, we developed a CSCs-specific targeted, RA-loaded GNSs-dPG nanoplatform for the targeted eradication of CSCs and for preventing the relapse.


Substantial susceptibility of chronic lymphocytic leukemia to BCL2 inhibition: results of a phase I study of navitoclax in patients with relapsed or refractory disease.
BCL2 overexpression is a hallmark of chronic lymphocytic leukemia (CLL). The novel BH3 mimetic navitoclax (ABT-263) specifically inhibits BCL2 and related proteins BCL-x(l) and BCL-w, potently inducing apoptosis of CLL cells in vitro. A phase I trial in patients with CLL was conducted to evaluate the safety, pharmacokinetics, and biologic activity of oral navitoclax. Twenty-nine patients with relapsed or refractory CLL received daily navitoclax for 14 days (10, 110, 200, or 250 mg/d; n = 15) or 21 days (125, 200, 250, or 300 mg/d; n = 14) of each 21-day cycle. Dose escalation decisions were informed by continual reassessment methodology. Lymphocytosis was reduced by more than 50% in 19 of 21 patients with baseline lymphocytosis. Among 26 patients treated with navitoclax ≥ 110 mg/d, nine (35%) achieved a partial response and seven maintained stable disease for more than 6 months. Median treatment duration was 7 months (range, 1 to ≥ 29 months). Median progression-free survival was 25 months. Activity was observed in patients with fludarabine-refractory disease, bulky adenopathy, and del(17p) CLL. Thrombocytopenia due to BCL-x(l) inhibition was the major dose-limiting toxicity and was dose-related. Low MCL1 expression and high BIM:MCL1 or BIM:BCL2 ratios in leukemic cells correlated with response. We determined that the navitoclax dose of 250 mg/d in a continuous dosing schedule was optimal for phase II studies. BCL2 is a valid therapeutic target in CLL, and its inhibition by navitoclax warrants further evaluation as monotherapy and in combination in this disease.


Inactivation of the mitogen-activated protein kinase pathway as a potential target-based therapy in ovarian serous tumors with KRAS or BRAF mutations.
Activation of mitogen-activated protein kinase (MAPK) occurs in response to various growth stimulating signals and as a result of activating mutations of the upstream regulators, KRAS and BRAF, which can be found in many types of human cancer. To investigate the roles of MAPK activation in tumors harboring KRAS or BRAF mutations, we inactivated MAPK in ovarian tumor cells using CI-1040, a compound that selectively inhibits MAPK kinase, an upstream regulator of MAPK and thus prevents MAPK activation. Profound growth inhibition and apoptosis were observed in CI-1040-treated tumor cells with mutations in either KRAS or BRAF in comparison with the ovarian cancer cells containing wild-type sequences. Long serial analysis of gene expression identified several differentially expressed genes in CI-1040-treated MPSC1 cells harboring an activating mutation in BRAF (V599L). The most striking changes were down-regulation of cyclin D1, COBRA1, and transglutaminase-2 and up-regulation of tumor necrosis factor-related apoptosis-induced ligand, thrombospondin-1, optineurin, and palladin. These patterns of gene expression were validated in other CI-1040-treated tumor cells based on quantitative PCR. Constitutive expression of cyclin D1 partially reversed the growth inhibitory effect of CI-1040 in MPSC1 cells. Our findings indicate that an activated MAPK pathway is critical in tumor growth and survival of ovarian tumors with KRAS or BRAF mutations and suggest that the CI-1040 induced phenotypes depend on the mutational status of KRAS and BRAF in ovarian tumors.


Anisakis simplex: sensitization and clinical allergy.
Whereas gastric anisakiasis has been known for several decades, the implications of Anisakis simplex-related allergic disorders had not been thoroughly studied until the late 1990s. This article reviews recent knowledge of allergic disorders ascribed to A. simplex contact or parasitism. Gastroallergic anisakiasis describes an acute hypersensitivity reaction emerging in the context of an acute parasitism by the nematode A. simplex. But other frequent allergic disorders like chronic urticaria are now being studied for a possible relationship with A. simplex parasitism. In recent investigations, non-IgE mediated mechanisms, such as the involvement of other immunoglobulin isotypes (IgG4), or non-immunological events are discussed. The experience of the last several years shows that allergic hypersensitivity symptoms in gastroallergic anisakiasis are clinical events accompanying a wide range of immunologic reactions as a host response against a ubiquitous parasite. The discussed and reviewed studies should motivate allergists around the world to search for this entity. Further studies in the field of allergy could benefit from the experience of this peculiar food-related disorder.


Anti-tumor-promoting activity of a polyphenolic fraction isolated from grape seeds in the mouse skin two-stage initiation-promotion protocol and identification of procyanidin B5-3'-gallate as the most effective antioxidant constituent.
Procyanidins present in grape seeds are known to exert anti-inflammatory, anti-arthritic and anti-allergic activities, prevent skin aging, scavenge oxygen free radicals and inhibit UV radiation-induced peroxidation activity. Since most of these events are associated with the tumor promotion stage of carcinogenesis, these studies suggest that grape seed polyphenols and the procyanidins present therein could be anticarcinogenic and/or anti-tumor-promoting agents. Therefore, we assessed the anti-tumor-promoting effect of a polyphenolic fraction isolated from grape seeds (GSP) employing the 7,12-dimethylbenz[a]anthracene (DMBA)-initiated and 12-O-tetradecanoylphorbol 13-acetate (TPA)-promoted SENCAR mouse skin two-stage carcinogenesis protocol as a model system. Following tumor initiation with DMBA, topical application of GSP at doses of 0.5 and 1.5 mg/mouse/application to the dorsal initiated mouse skin resulted in a highly significant inhibition of TPA tumor promotion. The observed anti-tumor-promoting effects of GSP were dose dependent and were evident in terms of a reduction in tumor incidence (35 and 60% inhibition), tumor multiplicity (61 and 83% inhibition) and tumor volume (67 and 87% inhibition) at both 0.5 and 1.5 mg GSP, respectively. Based on these results, we directed our efforts to separate and identify the individual polyphenols present in GSP and assess their antioxidant activity in terms of inhibition of epidermal lipid peroxidation. Employing HPLC followed by comparison with authentic standards for retention times in HPLC profiles, physiochemical properties and spectral analysis, nine individual polyphenols were identified as catechin, epicatechin, procyanidins B1-B5 and C1 and procyanidin B5-3'-gallate. Five of these individual polyphenols with evident structural differences, namely catechin, procyanidin B2, procyanidin B5, procyanidin C1 and procyanidin B5-3'-gallate, were assessed for antioxidant activity. All of them significantly inhibited epidermal lipid peroxidation, albeit to different levels. A structure-activity relationship study showed that with an increase in the degree of polymerization in polyphenol structure, the inhibitory potential towards lipid peroxidation increased. In addition, the position of linkage between inter-flavan units also influences lipid peroxidation activity; procyanidin isomers with a 4-6 linkage showed stronger inhibitory activity than isomers with a 4-8 linkage. A sharp increase in the inhibition of epidermal lipid peroxidation was also evident when a gallate group was linked at the 3'-hydroxy position of a procyanidin dimer. Procyanidin B5-3'-gallate showed the most potent antioxidant activity with an IC(50) of 20 microM in an epidermal lipid peroxidation assay. Taken together, for the first time these results show that grape seed polyphenols possess high anti-tumor-promoting activity due to the strong antioxidant effect of procyanidins present therein. In summary, grape seed polyphenols in general, and procyanidin B5-3'-gallate in particular, should be studied in more detail to be developed as cancer chemopreventive and/or anticarcinogenic agents.


Mammographic screening attendance among immigrant and minority women: a systematic review and meta-analysis.
Background Groups of immigrant and minority women are more often diagnosed with advanced stage breast cancer than other women. Mammographic screening aims to reduce mortality from breast cancer through early detection in asymptomatic women. Purpose To compare mammographic screening attendance among immigrant and minority women to that of other women. Material and Methods A literature search of PubMed, Embase, Google Scholar, and Cochrane identified 1369 papers published between January 1995 and March 2016. In the review, we included 33 studies investigating mammographic screening attendance among immigrant and/or minority women. In a meta-analysis, we included 19 of the studies that compared attendance among immigrant and/or minority women with that among other women, using a random effects model. Results The review included studies from Europe, North America, and Oceania, with 42,666,093 observations of opportunities for mammographic screening. Attendance was generally lower among immigrant and minority women compared to other women (46.2% vs. 55.0%; odds ratio = 0.64, 95% confidence interval = 0.56-0.73; P < 0.05, I2 = 99.9%). Non-Western immigrants had lower attendance rates than other immigrants. Conclusion Immigrant and minority women had lower mammographic screening attendance than other women, which could potentially put them at increased risk for more advanced breast cancer. This review emphasizes the importance of continued efforts to engage with the preventative health needs of diverse populations in attempts to achieve equality in access to, and use of, care.


Extrachromosomal element delta in Drosophila melanogaster. VII. Relation to fertility in a second-chromosome line.
The ID(b)-45 chromosome line usually carries an appreciable amount of delta b, but it is not susceptible to the killing action of this delta. The fertility of this line was examined when it carried various amounts of delta b. More than one third of the Cy/ID(b)-45 males and females tested became sterile when they carried cytoplasm of the Cy/Pm stock which is assumed to carry no delta b. The number of progeny is smaller when flies of this line are raised at 25 degrees C than at 28 degrees C at which temperature the multiplication of delta is accelerated. The progeny number was appreciably reduced when the flies were raised at 18 degrees C at which temperature the multiplication of delta is suppressed. This line could not be maintained at that temperature, since both males and females became sterile. Thus, the conclusion may be drawn that the presence of an appreciable amount of delta b is necessary for the gametogenesis of the Cy/ID(b)-45 flies.


Circulating and Pulmonary T-cell Populations Driving the Immune Response in Non-HIV Immunocompromised Patients with Pneumocystis jirovecii Pneumonia.
Background: Previous studies in human subjects have mostly been confined to peripheral blood lymphocytes for Pneumocystis infection. We here aimed to compare circulating and pulmonary T-cell populations derived from human immunodeficiency virus (HIV)-uninfected immunocompromised patients with Pneumocystis jirovecii pneumonia (PCP) in order to direct new therapies. Methods: Peripheral blood and bronchoalveolar lavage samples were collected from patients with and without PCP. Populations of Th1/Tc1, Th2/Tc2, Th9/Tc9, and Th17/Tc17 CD4+ and CD8+ T cells were quantified using multiparameter flow cytometry. Results: No significant differences were found between PCP and non-PCP groups in circulating T cells. However, significantly higher proportions of pulmonary Th1 and Tc9 were observed in the PCP than in the non-PCP group. Interestingly, our data indicated that pulmonary Th1 was negatively correlated with disease severity, whereas pulmonary Tc9 displayed a positive correlation in PCP patients. Conclusions: Our findings suggest that pulmonary expansion of Th1 and Tc9 subsets may play protective and detrimental roles in PCP patients, respectively. Thus, these specific T-cell subsets in the lungs may serve as targeted immunotherapies for patients with PCP.


OSU-03012 enhances Ad.7-induced GBM cell killing via ER stress and autophagy and by decreasing expression of mitochondrial protective proteins.
The present studies focused on determining whether the autophagy-inducing drug OSU-03012 (AR-12) could enhance the toxicity of recombinant adenoviral delivery of melanoma differentiation associated gene-7/interleukin-24 (mda-7/IL-24) in glioblastoma multiforme (GBM) cells. The toxicity of a recombinant adenovirus to express MDA-7/IL-24 (Ad.mda-7) was enhanced by OSU-03012 in a diverse panel of primary human GBM cells. The enhanced toxicity correlated with reduced ERK1/2 phosphorylation and expression of MCL-1 and BCL-XL, and was blocked by molecular activation of ERK1/2 and by inhibition of the intrinsic, but not the extrinsic, apoptosis pathway. Both OSU-03012 and expression of MDA-7/IL-24 increased phosphorylation of PKR-like endoplasmic reticulum kinase (PERK) that correlated with increased levels of autophagy and expression of dominant negative PERK blocked autophagy induction and tumor cell death. Knockdown of ATG5 or Beclin1 suppressed OSU-03012 enhanced MDA-7/IL-24-induced autophagy and blocked the lethal interaction between the two agents. Ad.mda-7-infected GBM cells secreted MDA-7/IL-24 into the growth media and this conditioned media induced expression of MDA-7/IL-24 in uninfected GBM cells. OSU-03012 interacted with conditioned media to kill GBM cells and knockdown of MDA-7/IL-24 in these cells suppressed tumor cell killing. Collectively, our data demonstrate that the induction of autophagy and mitochondrial dysfunction by a combinatorial treatment approach represents a potentially viable strategy to kill primary human GBM cells.


Prevalence and correlates of depressive symptoms among former prisoners of war.
Studies of former prisoners of war (POWs) provide valuable insights into posttraumatic adaptation because they gather information from a large population who survived the traumatic experiences of military captivity. Previous studies of POWs have shown elevated rates of psychiatric symptoms and disorders. This report presents evidence from a longitudinal study of three large, representative, national samples of former POWs. The study finds that depressive symptomatology, as measured by the Center for Epidemiologic Studies Depression Scale, is elevated in World War II POWs from the Pacific and European theaters and in Korean conflict POWs. Decades later, depressive symptomatology is found to be strongly associated with prior treatment in captivity. Differences in depressive symptomatology among the three POW groups can be attributed to captivity-related factors and to buffering factors, such as age at capture and education.


Solitary Prostate Carcinoma Penile Metastasis on 18 F-DCFPyL PET/CT.
An 83-year-old man was referred for an 18 F-DCFPyL PET scan for the evaluation of rising serum prostate-specific antigen level on the background of previous radical prostatectomy for prostate adenocarcinoma and urinary outflow tract obstruction requiring in-dwelling catheter insertion. The PET scan demonstrated focal increased activity (SUV max , 35.7) at the dorsal aspect of the mid penile shaft, with histopathological confirmation of penile metastasis from primary prostate cancer.


Long non-coding RNAs identify a subset of luminal muscle-invasive bladder cancer patients with favorable prognosis.
Muscle-invasive bladder cancer (MIBC) is a heterogeneous disease, and gene expression profiling has identified several molecular subtypes with distinct biological and clinicopathological characteristics. While MIBC subtyping has primarily been based on messenger RNA (mRNA), long non-coding RNAs (lncRNAs) may provide additional resolution. LncRNA expression was quantified from microarray data of a MIBC cohort treated with neoadjuvant chemotherapy (NAC) and radical cystectomy (RC) (n = 223). Unsupervised consensus clustering of highly variant lncRNAs identified a four-cluster solution, which was characterized using a panel of MIBC biomarkers, regulon activity profiles, gene signatures, and survival analysis. The four-cluster solution was confirmed in The Cancer Genome Atlas (TCGA) cohort (n = 405). A single-sample genomic classifier (GC) was trained using ridge-penalized logistic regression and validated in two independent cohorts (n = 255 and n = 94). NAC and TCGA cohorts both contained an lncRNA cluster (LC3) with favorable prognosis that was enriched with tumors of the luminal-papillary (LP) subtype. In both cohorts, patients with LP tumors in LC3 (LPL-C3) were younger and had organ-confined, node-negative disease. The LPL-C3 tumors had enhanced FGFR3, SHH, and wild-type p53 pathway activity. In the TCGA cohort, LPL-C3 tumors were enriched for FGFR3 mutations and depleted for TP53 and RB1 mutations. A GC trained to identify these LPL-C3 patients showed robust performance in two validation cohorts. Using lncRNA expression profiles, we identified a biologically distinct subgroup of luminal-papillary MIBC with a favorable prognosis. These data suggest that lncRNAs provide additional information for higher-resolution subtyping, potentially improving precision patient management.


Quality assessment of Penthorum chinense Pursh through multicomponent qualification and fingerprint, chemometric, and antihepatocarcinoma analyses.
An efficient method combined with fingerprint and chemometric analyses was developed to evaluate the quality of the traditional Chinese medicine plant Penthorum chinense Pursh. Nine samples were collected from different regions during different harvest periods, and 17 components in the form of extracts were simultaneously examined to assess quality by using high-performance liquid chromatography. The hepatoprotective effects of components were investigated by assessing the inhibition of SMMC-7721 cell growth. The results indicated that the quality control method was accurate, stable, and reliable, and the hierarchical heat-map cluster and the principle component analyses confirmed that the classification of all nine samples was consistent. Quercetin and ellagitannins including pinocembrin-7-O-[3''-O-galloyl-4'',6''-hexahydroxydiphenoyl]-β-glucose (PGHG), thonningianin A, thonningianin B, and other flavonoids were abundant in the extracts, and significantly contributed to the hepatoprotective effects.


Seasonal mood disturbances in collegiate hockey players.
THE PURPOSE OF THIS PAPER IS TO: 1) describe the seasonal affective disorder syndrome using a case illustration, 2) provide a simple and reliable method for identifying seasonal affective disorder, and 3) provide data as to the prevalence of the syndrome in a subset of collegiate hockey players. Collegiate hockey players were selected, because their practices begin in the fall and play is completed in the spring. The teams selected for participation were from the far Northwest and the upper Midwest regions. Sixty-eight Division I hockey players volunteered for the study. The three teams from which the subjects were chosen were located above latitude 42 degrees /45' north. Subjects were from the northern latitudes. The Seasonal Pattern Assessment Questionnaire was used to screen for seasonality. A sample of the athletes was also examined using the Hamilton Rating Scale for Depression together with the Diagnostic and Statistical Manual of Mental Disorders (4th ed) criteria for Seasonal Pattern Specifier. Thirty-three (51%) were asymptomatic, 7 (11%) met the criteria for seasonal affective disorder, and 25 (39%) hockey players scored in the range that could classify them as candidates for subsyndromal seasonal affective disorder. The prevalence of seasonal affective disorder among our sample approximated the national norm for the northern latitudes. However, the prevalence of subsyndromal seasonal affective disorder in our population was 25% compared to 13% reported nationally. Light therapy has been shown to reverse the effects of the disorders; however, further research needs to be conducted to determine its acceptance and effectiveness by the athletic population.


Helicobacter pylori NikR protein exhibits distinct conformations when bound to different promoters.
Helicobacter pylori NikR (HpNikR) is a ribbon-helix-helix (RHH) DNA-binding protein that binds to several different promoter regions. The binding site sequences are not absolutely conserved. The ability of HpNikR to discriminate specific DNA sites resides partly in its nine-amino acid N-terminal arm. Previously, indirect evidence indicated that the arm exists in different conformations when HpNikR is bound to the nixA and ureA promoters. Here, we directly examined HpNikR conformation when it was bound to nixA and ureA DNA fragments by tethering (S)-1{[bis(carboxymethyl)amino]methyl}-2-{4-[(2-bromoacetyl)amino]phenylethyl}(carboxymethyl)amino]acetic acid, iron(III) to different positions in the N-terminal arm and RHH DNA binding domain. Different cleavage patterns at each promoter directly demonstrated that both the RHH domain and the arm adopt different conformations on the nixA and ureA promoters. Additionally, the two RHH domain dimers of the HpNikR tetramer are in distinct conformations at ureA. Site-directed mutagenesis identified an interchain salt bridge (Lys(48)-Glu(47')) in the RHH domain remote from the DNA binding interface that is required for high affinity binding to ureA but not nixA. Finally, DNA affinity measurements of wild-type HpNikR and a salt bridge mutant (K48A) to hybrid nixA-ureA promoters demonstrated that inverted repeat half-sites, spacers, and flanking DNA are all required for sequence-specific DNA binding by HpNikR. Notably, the spacer region made the largest contribution to DNA affinity. HpNikR exhibits a substantially expanded regulon compared with other NikR proteins. The results presented here provide a molecular basis for understanding regulatory network expansion by NikR as well as other prokaryotic regulatory proteins.


Analysis of nucleotide insertion and extension at 8-oxo-7,8-dihydroguanine by replicative T7 polymerase exo- and human immunodeficiency virus-1 reverse transcriptase using steady-state and pre-steady-state kinetics.
Pre-steady-state kinetics of incorporation of dCTP and dATP opposite site-specific 8-oxo-7,8-dihydroguanine (8-oxoGua), in contrast to dCTP insertion opposite G, were examined as well as extension beyond the lesion using the replicative enzymes bacteriophage polymerase T7 exo- (T7-) and HIV-1 reverse transcriptase (RT). These results were compared to previous findings for Escherichia coli repair polymerases I (KF-) and II (pol II-) exo- [Lowe, L. G., & Guengerich, F. P. (1996) Biochemistry 35, 9840-9849]. HIV-1 RT showed a very high preference for insertion of dATP opposite 8-oxoGua, followed by pol II-, T7-, and KF-. Steady-state assays showed k(cat) consistently lower than pre-steady-state polymerization rates (k(p)) for insertion of dCTP opposite G or 8-oxoGua and insertion of dATP opposite 8-oxoGua. Pre-steady-state kinetic curves for the addition of dCTP opposite 8-oxoGua or G by KF-, pol II-, and T7- were all biphasic, with a rapid initial single-turnover burst followed by a slower multiple turnover rate, while addition of dATP opposite 8-oxoGua by these polymerases did not display burst kinetics. With HIV-1 RT, addition of dATP opposite 8-oxoGua displayed burst kinetics while addition of dCTP did not. Analyses of the chemical step by substitution of phosphorothioate analogs for normal dNTPs suggest that the chemistry is rate-limiting during addition of dCTP and dATP opposite 8-oxoGua by KF-, pol II-, and T7-; HIV- RT did not show a chemical rate-limiting step during addition of dATP opposite 8-oxoGua. Kinetic assays performed with various dCTP concentrations indicate that dCTP has a higher Kd and lower k(p) for incorporation opposite 8-oxoGua compared to G with all four enzymes. The K(d,app)dATP values for KF-, pol II-, and T7- incorporation of dATP opposite 8-oxoGua, estimated in competition assays, were found to be 3-10-fold greater than the K(d)dCTP. Likewise, the K(d,app)dCTP for HIV-1 RT incorporation of dCTP opposite 8-oxoGua was found to be 10-fold greater than the K(d)dATP. The repair enzymes (KF- and pol II-) efficiently extended the 8-oxoGua x A pair; extension of 8-oxoGua x C was severely impaired, whereas the replicative enzymes (T7- and HIV-1 RT) extended both pairs, with faster rates for the extension of the 8-oxoGua x A pair. On the basis of these findings, the fidelity of all four enzymes during replication of 8-oxoGua depends on contributions from the apparent Kd, the ease of base pair extension, and either the rate of conformational change before chemistry or the rate of bond formation.


Heritability of high sugar consumption through drinks and the genetic correlation with substance use.
High sugar consumption contributes to the rising prevalence of obesity. Sugar can have rewarding effects that are similar to, but less strong than, the effects of addictive substances. People who consume large amounts of sugar also tend to use more addictive substances, but it is unclear whether this is due to shared genetic or environmental risk factors. We examined whether there are genetic influences on the consumption of sugar-containing drinks and whether genetic factors can explain the association with substance use. The frequency of consumption of sugar-containing drinks (e.g., cola, soft drinks, and energy drinks) and addictive substances (nicotine, caffeine, alcohol, cannabis, and illicit drugs) was obtained for 8586 twins who were registered at the Netherlands Twin Register (women: 68.7%; mean ± SD age: 33.5 ± 15.3 y). Participants were categorized as high or low sugar consumers (>1 compared with ≤1 SD above daily consumption in grams) and as high or low substance users (≥2 compared with <2 substances). Through bivariate genetic modeling, genetic and environmental influences on sugar consumption, substance use, and their association were estimated. Genetic factors explained 48% of the variation in high sugar consumption, whereas unique environmental factors explained 52%. For high substance use, these values were 62% and 38%, respectively. There was a moderate phenotypic association between high sugar consumption and high substance use (r = 0.2), which was explained by genetic factors (59%) and unique environmental factors (41%). The positive association between high sugar consumption and high substance use was partly due to unique environmental factors (e.g., social situations). Genetic factors were also of influence, suggesting that neuronal circuits underlying the development of addiction and obesity are related. Further research is needed to identify genes that influence sugar consumption and those that overlap with substance use.


Effects of physical training on proprioception in older women.
Older adulthood is accompanied by declines in muscular strength, coordination, function, and increased risk of falling. Resistance training increases muscular strength in this population but its effect on proprioception is unknown. To evaluate the effect of resistance training on proprioception, community dwelling older women completed a three-month exercise study. A resistance training (RT) group (N=19) underwent supervised weight training three times per week while a non-strength trained control (NSTC) group (N=19) performed range-of-motion activities that mimicked the movements of the RT group without the benefit of muscle loading. Subjects were evaluated at baseline, 6, and 12 weeks for strength and proprioception. Muscular strength was assessed by measuring the subject's one repetition maximum performance on four different exercises. Static proprioception was measured by the subject's ability to reproduce a target knee joint angle while dynamic proprioception was measured by the subject's ability to detect passive knee motion. The RT group made significant strength improvements compared to the NSTC group. Proprioception significantly improved in both groups by 6 weeks. Our findings suggest that improvements in proprioception can be obtained via regular activity that is independent of heavy muscle loading.


Differential Responses of OsMPKs in IR56 Rice to Two BPH Populations of Different Virulence Levels.
The conserved mitogen-activated protein kinase (MAPK) cascades play vital roles in plant defense responses against pathogens and insects. In the current study, the expression profiles of 17 OsMPKs were determined in the TN1 and IR56 rice varieties under the infestation of brown planthopper (BPH), one of the most destructive hemimetabolous rice pests. The virulent IR56 BPH population (IR56-BPH) and the avirulent TN1 BPH population (TN-BPH) were used to reveal the roles of OsMPKs in the compatible (IR56-BPH infested on the TN1 and IR56 rice varieties, and TN1-BPH infested on the TN1 rice variety) and the incompatible (TN1-BPH infested on the IR56 rice variety) interaction. The statistical analysis revealed that rice variety, BPH population type, and infestation period have significant effects on the transcription of OsMPKs. Out of these genes, five OsMPKs (OsMPK1, OsMPK3, OsMPK7, OsMPK14, and OsMPK16) were found to exhibit upregulated expression only during incompatible interaction. Six OsMPKs (OsMPK4, OsMPK5, OsMPK8, OsMPK9, OsMPK12, and OsMPK13) were associated with both incompatible and compatible interactions. The transcription analysis of salicylic acid, jasmonic acid, and ethylene phytohormone signaling genes revealed their roles during the rice⁻BPH interactions. The upregulated expression of OsC4H, OsCHS, and OsCHI in the incompatible interaction implied the potential defense regulatory roles of phenylpropanoids. In both varieties, the elevated transcript accumulations of OsGST and OsSOD, and the increased enzyme activities of POD, SOD, and GST at 1 day post-infestation (dpi), but not at 3 dpi, indicated that reactive oxygen species (ROS) signaling might be an early event in rice⁻BPH interactions. Furthermore, upregulated transcription of OsLecRK3 and OsLecRK4 was found only during an incompatible interaction, suggesting their involvement in the BPH resistance response in the IR56 rice variety. Lastly, based on the findings of this study, we have proposed a model of interactions of IR56 rice with TN1-BPH and IR56-BPH that depicts the resistance and susceptibility reactions, respectively.


Developing and testing the effectiveness of a novel health qigong for frail elders in Hong Kong: a preliminary study.
Eight-Section Brocades and Yijin Jing consist of some routine movements that are too difficult for frail elders. A novel health qigong protocol was developed and its effectiveness for frail elders was examined using a randomized clinical trial (RCT). An expert panel performed functional anatomy analysis and safety field test prior to the RCT. The experimental group (n = 61, 83 ± 6 yr) was given a 12-week qigong exercise program, while the comparison group (n = 55, 84 ± 6 yr) participated in a newspaper reading program with the same duration and frequency. Pre-, mid-, post-, and follow-up assessments were conducted. At 12 weeks, the qigong group had significant improvements in thinking operations (F = 4.05, P = .02) and significant reduction of resting heart rate (F = 3.14, P = .045) as compared to the newspaper reading group. A trend of improvements in grip strength and a decreasing trend of depression levels were observed among the qigong group. Significant perceived improvements in physical health (F = 13.01, P = .001), activities of daily living (F = 5.32, P = .03), and overall health status (F = 15.26, P = .0001) were found. There are improvements in some aspects of psychosocial, cognitive, physical, and physiological domains. Clinical applications and possibilities for further research are discussed.


An economic evaluation of the Enhanced Recovery After Surgery (ERAS) multisite implementation program for colorectal surgery in Alberta
In February 2013, Alberta Health Services established an Enhanced Recovery After Surgery (ERAS) implementation program for adopting the ERAS Society colorectal guidelines into 6 sites (initial phase) that perform more than 75% of all colorectal surgeries in the province. We conducted an economic evaluation of this initiative to not only determine its cost-effectiveness, but also to inform strategy for the spread and scale of ERAS to other surgical protocols and sites. We assessed the impact of ERAS on patients' health services utilization (HSU; length of stay [LOS], readmissions, emergency department visits, general practitioner and specialist visits) within 30 days of discharge by comparing pre- and post-ERAS groups using multilevel negative binomial regressions. We estimated the net health care costs/savings and the return on investment (ROI) associated with those impacts for post-ERAS patients using a decision analytic modelling technique. We included 331 pre- and 1295 post-ERAS patients in our analyses. ERAS was associated with a reduction in all HSU outcomes except visits to specialists. However, only the reduction in primary LOS was significant. The net health system savings were estimated at $2 290 000 (range $1 191 000–$3 391 000), or $1768 (range $920–$2619) per patient. The probability for the program to be cost-saving was 73%–83%. In terms of ROI, every $1 invested in ERAS would bring $3.8 (range $2.4–$5.1) in return. The initial phase of ERAS implementation for colorectal surgery in Alberta is cost-saving. The total savings has the potential to be more substantial when ERAS is spread for other surgical protocols and across additional sites.


Association between aminotransferase/alanine aminotransferase ratio and cardiovascular disease mortality in patients on peritoneal dialysis: a multi-center retrospective study.
Elevated aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio is an independent risk factor for cardiovascular disease (CVD) among the general population. However, an association between AST/ALT ratio and CVD mortality in patients on peritoneal dialysis (PD) has received little attention. A total of 2224 incident PD patients from multi-centers were enrolled from November 1, 2005, to June 30, 2017, in this retrospective cohort study. The primary endpoint was CVD mortality. Eligible patients were divided into high and normal groups according to the AST/ALT ratio cut-off for CVD mortality with the receiver operating characteristic (ROC) curve. The associations between the AST/ALT ratio and CVD mortality were evaluated by the Cox regression model. Of eligible 1579 patients with a mean age of 49.3 ± 14.6 years, 55.4% of patients were male, 18.1% of patients had diabetes, and 64.2% of patients had hypertension. The prevalence of a high AST/ALT ratio was 76.6% in the cohort population. During a follow-up period with 4659.6 patient-years, 316 patients died, of which 193 (61.1%) deaths were caused by CVD episodes. The incidence of CVD mortality in the high group was significantly higher than that in the normal group (13.1% versus 9.2%, P = 0.024). Cumulative CVD mortality rates were significantly different between the two groups by Kaplan-Meier analysis [hazards ratio (HR) = 1.50, 95% confidence index (CI) 1.09-2.07, P = 0.014]. After adjusting for confounding factors, a higher AST/ALT ratio was independently associated with an increased risk of CVD mortality compared with their counterparts (HR = 1.43, 95%CI 1.08-2.41, P = 0.002). PD patients with high baseline AST/ALT ratio levels may be at a significant risk of CVD mortality.


Suicide and family loading for affective disorders.
All suicides were ascertained for a 100-year period (1880 to 1980) in a study of mental illness among the Old Order Amish. The majority (92%) of the 26 cases were diagnosed with a major affective disorder and were situated in multigenerational families with heavy loading for bipolar, unipolar, and other affective-spectrum illnesses. The suicides clustered in four primary pedigrees, and the role of inheritance was suggested by the way in which suicides followed the distribution of affective disorders in these kinship lines. We believe these extended pedigrees provide presumptive evidence of genetic factors in both suicides and affective disorders.


Dietary Supplement Use, Knowledge, and Perceptions Among Student Pharmacists.
Objective. To compare dietary supplement use between student pharmacists and the general population, and assess knowledge, attitudes toward use, and dietary supplement effectiveness; and to explore how student pharmacists view their education on dietary supplements. Methods. Paper questionnaires administered to student pharmacists collected data about their use, knowledge, and attitudes of dietary supplements. Use was compared to the 2007 National Health Interview survey findings. Results. Of 179 students who responded, 52% had used at least one dietary supplement in their lifetime versus 25% in the general population. Students perceived supplement label information as unhelpful, research into supplements inadequate, and supplements non-essential to health. Students thought supplement knowledge was important but their education was inadequate. Conclusion. Dietary supplement use was higher in this sample of student pharmacists than the general population. Student pharmacists had limited knowledge and need more education on dietary supplements.


Assessment of working memory in children with attention-deficit/hyperactivity disorder.
This research investigated the cognitive abilities and the working memory in children and youngsters with three different types of attention-deficit/hyperactivity disorder (ADHD): (a) mainly with attention-deficit, (b) hyperactive and impulsive, and (c) combined. A computerized test called Infant Cognitive Abilities Test, which measures five cognitive abilities based on the Cattell-Horn-Carroll model, was used. Thirty-two children from both sexes, aged 7 to 15 years, from the Hospital das Clínicas, suffering from ADHD and a control group with 30 children from a state elementary school (first through eighth grades) were submitted to the test. The results showed that there were significant differences with regard to the reaction time of the working memory of the different types of ADHD. Children suffering from ADHD had high test scores for the visual memory items of the test, when compared with the results in the auditory memory items.


Reduction of catheter-related bloodstream infections in preterm infants by the use of catheters with the AgION antimicrobial system.
The present study aims to assess if use of a silver zeolite-impregnated umbilical catheter (AgION technology) can decrease the occurrence of catheter-related bloodstream infection (CRBSIs) in preterm infants. Infants with gestational age<30weeks were randomized to receive an AgION impregnated or non-impregnated polyurethane umbilical venous catheter (UVC). The primary endpoint was the incidence of CRBSIs during the time the UVC was in place. We studied 86 infants, 41 of whom received the AgION catheter and 45 the non-impregnated catheter. During umbilical venous catheterization 2% of infants in the AgION group developed CRBSI in comparison with 22% of infants in the control group (p=0.005). AgION catheters were well tolerated and none of the patients showed signs attributable to silver toxicity. The AgION-impregnated UVCs were effective in decreasing the development of CRBSIs in preterm infants compared to non-impregnated polyurethane UVCs.


Analysis of toxicity of streptococcal pyrogenic exotoxin A mutants.
Streptococcal pyrogenic exotoxin A (SPE A) is secreted by some strains of Streptococcus pyogenes and is strongly associated with streptococcal toxic shock syndrome (STSS), a severe and often fatal illness. SPE A possesses a number of biological properties, some of which are shared with a group of exotoxins of streptococcal and staphylococcal origins, the pyrogenic toxin superantigens (PTSAgs). SPE A's most extensively studied property is superantigenicity. Superantigenic activation of T cells and monocytes stimulates the release of cytokines such as tumor necrosis factors alpha and beta, interleukin 1, and gamma interferon. These endogenous mediators are considered to be the primary cause of capillary leak, hypotension, and shock, the most severe manifestations of STSS. However, several studies have suggested that other properties of SPE A, such as ability to greatly enhance host susceptibility to endotoxin and ability to interact directly with endothelial cells, may play substantial roles in the syndrome. In this work we generated single- and double-site mutations of SPE A at residues K16, N20, C87, C90, C98, K157, S195, N20/C98, and N20/K157. The mutant SPE A's were analyzed in vivo for their lethal activity and in vitro for their superantigenic ability. Our results indicate that SPE A's ability to induce lethality and endotoxin enhancement does not require superantigenicity, and conversely superantigenicity does not necessarily lead to lethality. Thus, these properties and their relative contributions to the onset of hypotension and shock may be separable. Furthermore, evidence is presented that certain mutant toxins may be suitable for use as vaccine toxoids.


OBRA '87: has it resulted in better quality of care?
This study examines perspectives of a broad group of nursing home employees, regulators, advocates, and professional associations to describe progress made since the 1990 implementation of the Nursing Home Reform legislation (OBRA '87) and to determine whether the legislation is perceived as affecting positive change for nursing home residents. Interviews were conducted with 59 residents and 132 professional and non-professional staff in six states. Important quality of care issues of resident rights, resident dignity, restraint use, resident assessment, as well as perspectives of residents themselves are explored. In general, OBRA '87 is viewed as positive, with all groups of respondents indicating that residents have benefited from it. They identify the focus on resident rights as the most important accomplishment. Empowerment of residents through involvement in care decisions is noted by many as an important achievement. Many conclude that quality of care has improved and restraint use has decreased. The MDS is a useful tool from the standpoint of nursing home staff and regulators. This appraisal sharply contrasts their opinions about the Preadmission Screening and Resident Review (PASARR) screening tool. We believe that PASARR should be reexamined and that changes should be made in the process and/or implementation of the tool.


Normal breast lobular architecture in breast biopsy samples from breast cancer cases and benign disease controls.
Rodent studies suggest a relationship between lobular maturation and breast cancer risk. Human data are sparse, and were developed using whole mounts of mastectomy or mammoplasty samples, without consideration of menstrual phase in premenopausal women. We studied normal breast lobules in relation to cancer risk in 284 women, using surgical biopsy material (mean two sections and 43.2 lobular structures per subject): 167 were premenopausal; 89 with breast cancer (cases) and 78 undergoing benign breast biopsy (controls). Of 117 postmenopausal women, 67 were cases and 50 were controls. Normal lobular type was classified based on size, and was designated predominant if it constituted 60% or more of the total lobules classified. The control group showed 66% type I, 34% type II and 1% type III lobules while cases showed 69% type I, 31% type II and 7% type III structures. Predominant lobule type showed no association with cancer (p = 0.9). Postmenopausal women had a substantially higher proportion of type I lobules compared to premenopausal women, irrespective of the parity or cancer status (p < 0.001). Lobule type was not associated with menstrual phase classified by dates; however, when menstrual phase was classified using breast morphological characteristics, type I lobules were more abundant in follicular phase and type II in the luteal phase (p < 0.001). In conclusion, we did not observe a relationship between lobular architecture and breast cancer susceptibility when using smaller breast samples usually available in epidemiological studies, but these data highlight the need for menstrual phase stratification in future investigations.


Effect of Aldosterone on Senescence and Proliferation Inhibition of Endothelial Progenitor Cells Induced by Sirtuin 1 (SIRT1) in Pulmonary Arterial Hypertension.
BACKGROUND Pulmonary arterial hypertension (PAH) is characterized by a progressive increase in pulmonary circulatory resistance. Pulmonary vascular endothelial dysfunction is one of the main causes of primary PAH. Endothelial progenitor cells (EPCs) can proliferate and differentiate into vascular endothelial cells and play an important role in maintaining normal endothelial function. Mineralocorticoid receptor inhibitor has been reported to be used in the treatment of PAH. However, the role and the underlying mechanism of aldosterone (ALDO) in PAH remains unclear. MATERIAL AND METHODS Rats were divided to 4 groups (n=10 per group) and treated with 0.9% normal saline, monocrotaline (MCT), spironolactone (SP), or MCT combined with SP. After the rats were sacrificed with an overdose of pentobarbital sodium, hematoxylin and eosin staining was performed to observe the pulmonary artery pathology section. Sirtuin 1 (SIRT1), p53, and p21 protein expression was detect by western blot. Immunofluorescence staining was performed to verify EPCs. EPCs were treated with different concentrations of ALDO. MTT assay and senescence-associated ß-galactosidase staining were used to measure cell viability and senescence. RESULTS MCT increased the vascular arterial wall thickness and wall area, inhibited SIRT1 protein expression and increased p53 and p21 protein expression in the lung tissue of rats, while SP partially reversed this effect. In addition, ALDO inhibited EPCs viability and induced senescence. The expression of p53 and p21 proteins in the EPCs were upregulated and the senescence was accelerated when EPCs were transfected with SIRT1 siRNA. CONCLUSIONS ALDO promoted EPCs senescence and inhibited EPCs proliferation by downregulating SIRT1, which regulates the p53/p21 pathway, thus promoting PAH.


Factors Affecting Insulin Resistance and Its Relation to Vitamin D Status and Clinical Nutritional Parameters in Dialysis Patients: A Single-center Indian Study.
The aim of this study was to measure insulin resistance (IR) in dialysis patients and its relation to Vitamin D status and nutritional parameters. We included patients on maintenance dialysis, both hemodialysis and peritoneal dialysis (HD and PD). IR was measured by homeostatic model assessment (HOMA)-IR index defined as fasting serum insulin (μU/L) × fasting blood sugar (mmol/L)/22.5. Baseline Vitamin D levels were measured by chemiluminescence immunoassay (CLIA) method. HOMA-IR index correlated with nutritional parameters such as 7-point subjective global assessment (SGA) and anthropometric measures, for example, body fat percentage, lean body weight (LBW), mid-arm circumference (MAC), and mid-arm muscle circumference (MAMC). A total of 55 patients were studied, of them 74.55% were male with mean age of the study population being 37.44 ± 14.96 years. The prevalence values of Vitamin D deficiency <30 ngm/ml, <20 ngm/ml, and <10 ngm/ml levels were 96.36%, 70.91%, and 23.64%, respectively. Mean HOMA-IR index was 3.14 ± 3.86. The correlation of HOMA-IR with Vitamin D was negative (r = -0.140, 95% confidence interval [CI] = -0.397-0.138 and P = 0.309); however, in subgroup analysis, patients with Vitamin D level <20 ng/ml had significantly high IR compared to those with Vitamin D >20 ng/ml, i.e., 3.74 ± 4.37 and 1.67 ± 1.47, respectively (P = 0.018). The other measured parameter which had a significant positive correlation with IR was serum uric acid (r = 0.303, 95% CI = 0.021-0.534, and P = 0.025). In nutritional assessment, body mass index, MAC, and MAMC had statistically significant positive correlation with HOMA-IR index (P ≤ 0.001, 0.004, and 0.004, respectively) unlike SGA (P = 0.480). The mode of dialysis did not have a significant effect on IR (HD vs. PD, P = 0.227). The majority of the patients on maintenance dialysis are Vitamin D deficient. Low Vitamin D level, especially <20 ng/ml, muscle mass, and high serum uric acid level are likely to have more IR in dialysis-dependent patients.


Does zinc moderate essential fatty acid and amphetamine treatment of attention-deficit/hyperactivity disorder?
Zinc is an important co-factor for metabolism relevant to neurotransmitters, fatty acids, prostaglandins, and melatonin, and indirectly affects dopamine metabolism, believed intimately involved in attention-deficit/hyperactivity disorder (ADHD). To explore the relationship of zinc nutrition to essential fatty acid supplement and stimulant effects in treatment of ADHD, we re-analyzed data from an 18-subject double-blind, placebo-controlled crossover treatment comparison of d-amphetamine and Efamol (evening primrose oil, rich in gamma-linolenic acid). Subjects were categorized as zinc-adequate (n = 5), borderline zinc (n = 5), and zinc-deficient (n = 8) by hair, red cell, and urine zinc levels; for each category, placebo-active difference means were calculated on teachers' ratings. Placebo-controlled d-amphetamine response appeared linear with zinc nutrition, but the relationship of Efamol response to zinc appeared U-shaped; Efamol benefit was evident only with borderline zinc. Placebo-controlled effect size (Cohen's d) for both treatments ranged up to 1.5 for borderline zinc and dropped to 0.3-0.7 with mild zinc deficiency. If upheld by prospective research, this post-hoc exploration suggests that zinc nutrition may be important for treatment of ADHD even by pharmacotherapy, and if Efamol benefits ADHD, it likely does so by improving or compensating for borderline zinc nutrition.


A Mouse Model of SARS-CoV-2 Infection and Pathogenesis.
Since December 2019, a novel coronavirus SARS-CoV-2 has emerged and rapidly spread throughout the world, resulting in a global public health emergency. The lack of vaccine and antivirals has brought an urgent need for an animal model. Human angiotensin-converting enzyme II (ACE2) has been identified as a functional receptor for SARS-CoV-2. In this study, we generated a mouse model expressing human ACE2 (hACE2) by using CRISPR/Cas9 knockin technology. In comparison with wild-type C57BL/6 mice, both young and aged hACE2 mice sustained high viral loads in lung, trachea, and brain upon intranasal infection. Although fatalities were not observed, interstitial pneumonia and elevated cytokines were seen in SARS-CoV-2 infected-aged hACE2 mice. Interestingly, intragastric inoculation of SARS-CoV-2 was seen to cause productive infection and lead to pulmonary pathological changes in hACE2 mice. Overall, this animal model described here provides a useful tool for studying SARS-CoV-2 transmission and pathogenesis and evaluating COVID-19 vaccines and therapeutics.


CDKL5-mediated developmental tuning of neuronal excitability and concomitant regulation of transcriptome.
Cyclin-dependent kinase-like 5 (CDKL5) is a serine-threonine kinase enriched in the forebrain to regulate neuronal development and function. Patients with CDKL5 deficiency disorder (CDD), a severe neurodevelopmental condition caused by mutations of CDKL5 gene, present early-onset epilepsy as the most prominent feature. However, spontaneous seizures have not been reported in mouse models of CDD, raising vital questions on the human-mouse differences and the roles of CDKL5 in early postnatal brains. Here, we firstly measured electroencephalographic (EEG) activities via a wireless telemetry system coupled with video-recording in neonatal mice. We found that mice lacking CDKL5 exhibited spontaneous epileptic EEG discharges, accompanied with increased burst activities and ictal behaviors, specifically at postnatal day 12 (P12). Intriguingly, those epileptic spikes disappeared after P14. We next performed an unbiased transcriptome profiling in the dorsal hippocampus and motor cortex of Cdkl5 null mice at different developmental timepoints, uncovering a set of age-dependent and brain region-specific alterations of gene expression in parallel with the transient display of epileptic activities. Finally, we validated multiple differentially expressed genes, such as glycine receptor alpha 2 and cholecystokinin, at the transcript or protein levels, supporting the relevance of these genes to CDKL5-regulated excitability. Our findings reveal early-onset neuronal hyperexcitability in mouse model of CDD, providing new insights into CDD etiology and potential molecular targets to ameliorate intractable neonatal epilepsy.


A randomized, controlled trial of the effects of resveratrol administration in performance horses with lameness localized to the distal tarsal joints.
OBJECTIVE To determine the effect of resveratrol administration in performance horses with lameness localized to the distal tarsal joints. DESIGN Randomized, blinded, placebo-controlled clinical trial. ANIMALS 45 client-owned horses with lameness localized to the distal tarsal joints. PROCEDURES All horses received injections of triamcinolone acetonide in the centrodistal and tarsometatarsal joints of both hind limbs. A placebo or a supplement containing resveratrol was fed twice daily by owners for 4 months. Primary outcomes were horse performance as determined by rider opinion (better, worse, or the same) and change in lameness severity from the enrollment examination. RESULTS Complete data were obtained for 21 horses that received resveratrol and 20 that received the placebo. Percentage of riders who reported that the horse's performance was better, compared with worse or the same, was significantly higher for the resveratrol group than for the placebo group after 2 (20/21 [95%] vs 14/20 [70%]) and 4 (18/21 [86%] vs 10/20 [50%]) months. The change in A1:A2 ratio between the enrollment and 4-month recheck examinations was significantly better for horses in the resveratrol versus placebo group. However, subjective lameness scores and degree of asymmetry of pelvis movement did not differ between groups. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that in performance horses with lameness localized to the distal tarsal joints, injection of triamcinolone in the centrodistal and tarsometatarsal joints of both hind limbs followed by oral supplementation with resveratrol for 4 months resulted in reduced lameness, compared with triamcinolone injection and supplementation with a placebo.


Preweaning piglet mortality in relation to placental efficiency.
The relationship between placental efficiency (PLEFF, i.e., the ratio of birth weight [BWB] to placental weight [PLW]) and neonatal pig vitality as measured by the probability of preweaning death of live born piglets was examined for 1,036 live born piglets of 118 litters. The data were first analyzed to establish whether the relationships between PLEFF, PLW, and BWB were affected by parity (first vs. higher). Furthermore, the data collected were used to establish whether PLEFF is a better predictor of the risk of neonatal pig mortality before weaning than BWB and PLW. The relationships of BWB to PLW and PLEFF to PLW differed (P <0.01 and P <0.05, respectively) between piglets from gilts and sows. This difference appeared to be due mainly to an additional population of piglets with very large placentas in sows that were not present in gilts. Despite being significant, the courses of the relationships were essentially similar for piglets in gilts and in sows. For the curvilinear relationship of BWB to PLW, up to a certain threshold value, an increase of PLW resulted in an increase in BWB, and thereafter BWB did not change. A consequence of this is that PLEFF at relatively high PLW does not give the same information as PLEFF at relatively low PLW. For the second-order relationship of PLEFF to BWB, PLEFF increased with an increase in BWB, until BWB = 1,657 g, and decreased thereafter. The PLEFF decreased linearly with PLW. A change in PLW had a much larger impact on the value of PLEFF than a change in BWB. Although BWB and PLW were negatively associated with the chance of dying before weaning (P <0.001 and P <0.01, respectively), only PLEFF tended to be negatively associated with the chance of dying only before weaning (P = 0.08). Its underlying trait, BWB, played a greater role on the effect of PLEFF on the chance of preweaning death than PLW. In conclusion, PLEFF in swine is a complicated trait that should be treated with care. It is merely a mathematical derivative of BWB and PLW, whereby the extent to which BWB depends on PLW depends on the value of PLW. Placental functioning and fetal growth capacity, however, also have their effects on the value of BWB. It is concluded that, of the three traits (BWB, PLW, and PLEFF), the best predictor for the chance of preweaning mortality, which also happens to be easiest to measure, remains BWB.


Characterization of Chlamydia trachomatis plasmid-encoded open reading frames.
The recent success in transformation of Chlamydia trachomatis represents a major advancement in Chlamydia research. Plasmid-free C. trachomatis serovar L2 organisms can be transformed with chlamydial plasmid-based shuttle vectors pGFP::SW2 and pBRCT. Deletion of plasmid genes coding for Pgp1 to Pgp8 in pBRCT led to the identification of Pgp1, -2, -6, and -8 as plasmid maintenance factors; Pgp4 as a transcriptional regulator of chlamydial virulence-associated gene expression; and Pgp3, -5, and -7 as being dispensable for chlamydial growth in vitro. Using the pGFP::SW2 vector system, we confirmed these findings in the current report. To further dissect the roles of pgp coding sequences and Pgp proteins in plasmid maintenance, we introduced premature stop codons into the pgp genes. Stable transformants were obtained with pGFP::SW2 derivatives carrying premature stop codons in pgp8 but not in pgp1, pgp2, and pgp6, suggesting that the pgp8 coding sequence but not the Pgp8 protein is required for maintaining the plasmid, while Pgp1, -2, and -6 proteins are necessary for plasmid maintenance. We also found that a minimum of 30 nucleotides in the pgp3 coding region was required for pgp4 expression. Finally, mCherry red fluorescent protein was successfully expressed when the mCherry gene was used to replace the pgp3, pgp4, or pgp5 coding region, indicating that these regions can be used to express nonchlamydial genes in chlamydial organisms. These novel observations have provided information for further use of chlamydial plasmid shuttle vectors as genetic tools to understand chlamydial biology and pathogenicity as well as to develop attenuated chlamydial vaccines.


Kinetic stabilization of an oligomeric protein under physiological conditions demonstrated by a lack of subunit exchange: implications for transthyretin amyloidosis.
Kinetic stabilization of transthyretin (TTR) is established to prevent human neurodegeneration. Therefore, small molecule-mediated kinetic stabilization of the native state is an attractive strategy to prevent the misfolding and misassembly associated with TTR amyloid disease. Since the physiological microenvironment resulting in human TTR amyloidogenesis remains unclear, the conservative approach is to identify inhibitors that function under a variety of conditions. Small molecule kinetic stabilization of TTR has been established by concentration-dependent inhibition of acid-mediated amyloidogenesis and urea-induced tetramer dissociation. Since denaturing conditions reduce the binding affinity of inhibitors making it difficult to predict inhibitor efficacy under physiological conditions, we introduce a method for quantifying kinetic stabilization under physiological conditions. The rate of subunit exchange between wild-type TTR homotetramers and wild-type TTR homotetramers tagged with an N-terminal acidic flag tag is dictated by the rate of tetramer dissociation to its monomeric subunits prior to reassembly, rendering this method ideally suited for assessing the kinetic stabilization of TTR imparted by small molecule binding and evaluating small molecule binding constants. Addition of amyloidogenesis inhibitors to this exchange reaction slows tetramer dissociation in a concentration-dependent manner, stopping dissociation at concentrations where at least one inhibitor is bound to each tetramer in solution. Subunit exchange enables the rate of tetramer dissociation and the kinetic stabilization imparted by small molecule binding to be evaluated under physiological conditions in which the TTR concentration is not reduced by aggregation or irreversible dissociation.


Population structure of wild bananas, Musa balbisiana, in China determined by SSR fingerprinting and cpDNA PCR-RFLP.
Both demographic history and dispersal mechanisms influence the apportionment of genetic diversity among plant populations across geographical regions. In this study, phylogeography and population structure of wild banana, Musa balbisiana, one of the progenitors of cultivated bananas and plantains in China were investigated by an analysis of genetic diversity of simple sequence repeat (SSR) fingerprint markers and cpDNA PCR-RFLP. A chloroplast DNA (cpDNA) genealogy of 21 haplotypes identified two major clades, which correspond to two geographical regions separated by the Beijiang and Xijiang rivers, suggesting a history of vicariance. Significant genetic differentiation was detected among populations with cpDNA markers, a result consistent with limited seed dispersal in wild banana mediated by foraging of rodents. Nuclear SSR data also revealed significant geographical structuring in banana populations. In western China, however, there was no detected phylogeograpahical pattern, possibly due to frequent pollen flow via fruit bats. In contrast, populations east of the Beijiang River and the population of Hainan Island, where long-range soaring pollinators are absent, are genetically distinct. Colonization-extinction processes may have influenced the evolution of Musa populations, which have a metapopulation structure and are connected by migrating individuals. Effective gene flow via pollen, estimated from the nuclear SSR data, is 3.65 times greater than gene flow via seed, estimated from cpDNA data. Chloroplast and nuclear DNAs provide different insights into phylogeographical patterns of wild banana populations and, taken together, can inform conservation practices.


Identification and characterization of a sphingolipid delta 4-desaturase family.
Sphingolipids desaturated at the Delta4-position are important signaling molecules in many eukaryotic organisms, including mammals. In a bioinformatics approach, we now identified a new family of protein sequences from animals, plants, and fungi and characterized these sequences biochemically by expression in Saccharomyces cerevisiae. This resulted in the identification of the enzyme sphingolipid Delta4-desaturase (dihydroceramide desaturase) from Homo sapiens, Mus musculus, Drosophila melanogaster, and Candida albicans, in addition to a bifunctional sphingolipid Delta4-desaturase/C-4-hydroxylase from M. musculus. Among the sequences investigated are the Homo sapiens membrane lipid desaturase, the M. musculus degenerative spermatocyte, and the Drosophila melanogaster degenerative spermatocyte proteins. During spermatogenesis, but not oogenesis of des mutant flies, both cell cycle and spermatid differentiation are specifically blocked at the entry into the first meiotic division, leading to male sterility. This mutant phenotype can be restored to wild-type by complementation with a functional copy of the des gene (Endo, K., Akiyama, T., Kobayashi S., and Okada, M. (1996) Mol. Gen. Genet. 253, 157-165). These results suggest that Delta4-desaturated sphingolipids provide an early signal necessary to trigger the entry into both meiotic and spermatid differentiation pathways during Drosophila spermatogenesis.


Neck infection associated with pyriform sinus fistula: imaging findings.
Acute suppurative neck infections associated with branchial fistulas are frequently recurrent. In this study, we describe the imaging findings of acute suppurative infection of the neck caused by a third or fourth branchial fistula (pyriform sinus fistula). Imaging findings were reviewed in 17 patients (11 female and six male patients, 2 to 49 years old) with neck infection associated with pyriform sinus fistula. Surgery or laryngoscopic examination confirmed the diagnoses. Fourteen patients had a history of recurrent neck infection and seven had cutaneous openings on the anterior portion of the neck (all lesions were on the left side). Imaging studies included barium esophagography (n = 16), CT (n = 14), MR imaging (n = 2), and sonography (n = 3). A sinus or fistulous tract was identified in eight of 16 patients on barium esophagograms. In 14 patients, CT studies showed the inflammatory infiltration and/or abscess formation along the course of the sinus or fistulous tract from the pyriform fossa to the thyroid gland. In nine patients, CT scans showed the entire course or a part of the sinus or fistulous tract as a tiny spot containing air. MR images showed a sinus or fistulous tract in two patients, whereas sonograms could not depict a sinus or fistulous tract in three patients. All 17 patients were treated with antibiotics. In one patient, the sinus tract was surgically excised, while 15 patients underwent chemocauterization of the sinus or fistulous tract with good outcome. Follow-up was possible for 16 of the 17 patients. When an inflammatory infiltration or abscess is present between the pyriform fossa and the thyroid bed in the lower left part of the neck, an infected third or fourth branchial fistula should be strongly suspected.


Trait Mindfulness Predicts Efficient Top-Down Attention to and Discrimination of Facial Expressions.
In social situations, skillful regulation of emotion and behavior depends on efficiently discerning others' emotions. Identifying factors that promote timely and accurate discernment of facial expressions can therefore advance understanding of social emotion regulation and behavior. The present research examined whether trait mindfulness predicts neural and behavioral markers of early top-down attention to, and efficient discrimination of, socioemotional stimuli. Attention-based event-related potentials (ERPs) and behavioral responses were recorded while participants (N = 62; White; 67% female; Mage = 19.09 years, SD = 2.14 years) completed an emotional go/no-go task involving happy, neutral, and fearful facial expressions. Mindfulness predicted larger (more negative) N100 and N200 ERP amplitudes to both go and no-go stimuli. Mindfulness also predicted faster response time that was not attributable to a speed-accuracy trade-off. Significant relations held after accounting for attentional control or social anxiety. This study adds neurophysiological support for foundational accounts that mindfulness entails moment-to-moment attention with lower tendencies toward habitual patterns of responding. Mindfulness may enhance the quality of social behavior in socioemotional contexts by promoting efficient top-down attention to and discrimination of others' emotions, alongside greater monitoring and inhibition of automatic response tendencies.


Functional treatment of a large laryngeal chondrosarcoma by tracheal autotransplantation.
Chondrosarcoma of the cricoid cartilage poses difficult therapeutic challenges. The tumor necessitates resection of parts of the cricoid cartilage with a resulting defect that is difficult to repair. We wanted to improve the functional outcome after resection of a lateralized chondrosarcoma by applying the technique of tracheal autotransplantation. The technique involves a 2-stage procedure, because the trachea needs at least 2 weeks for revascularization. Tracheal revascularization is the first stage, and is accomplished by wrapping the trachea in vascularized fascia (radial forearm). The second stage, performed after 14 days, consists of a hemilaryngectomy with tracheal autotransplantation. A case of a large unilateral chondrosarcoma of the cricoid cartilage with involvement of 1 cricoarytenoid joint is reported. The tumor was removed by hemicricohemilaryngectomy. After 2 weeks of tracheal revascularization, the cervical trachea was used to repair the laryngeal defect. The tumor was completely resected, and all laryngeal functions (swallowing, voice, respiration without tracheostomy) were restored. The patient remains tumor-free after a follow-up period of 3 years. Tracheal autotransplantation improves the functional treatment of lateralized chondrosarcomas of the cricoid cartilage.


Food parenting topics in social media posts: Development of a coding system, examination of frequency of food parenting concepts, and comparison across Reddit and Facebook.
This study presents development of a coding system to examine food parenting topics presented in posts on social media, and compared topics between two social media platforms (Facebook, Reddit). Publicly available social media posts were gathered from Facebook (2 groups) and Reddit (3 subreddits) and a coding system was developed based on the concept map of food parenting proposed by Vaughn et al. (2016). Based on the developed coding system, we coded posts into overarching food parenting practice constructs (coercive control: attempts to dominate, pressure or impose parents' will on child, structure: organization of child's environment to facilitate competence, autonomy support: supporting child's ability to self-regulate through allowing food choices, conversations about food, and a positive emotional climate) and recipes. We also coded posts dichotomously as including a question or advice-seeking. Differences in frequencies of food parenting constructs presented in posts on Facebook and Reddit were considered using chi-square tests of independence. Of the 2459 posts coded, 900 were related to food parenting (37%). In the subsample of 900, posts related to structure (43%) and recipes (40%) were the most frequent. Close to half of the posts (44%) included questions about food parenting. Frequency of food parenting topics in posts was related to social media platform, with coercive control and structure more frequently discussed on Reddit and recipes more commonly posted on Facebook. Results suggest that food parenting topics discuss on social media differ by platform, which can aid researchers and practitioners in targeting social media-based outreach to the topics of most interest for users. Findings give insight into the everyday food parenting topics and questions that parents and caregivers may be exposed to on social media. TAXONOMY: Development of Feeding; Parenting; Online Information Services.


Effect of stimulus-driven pruning on the detection of spatiotemporal patterns of activity in large neural networks.
Adult patterns of neuronal connectivity develop from a transient embryonic template characterized by exuberant projections to both appropriate and inappropriate target regions in a process known as synaptic pruning. Trigger signals able to induce synaptic pruning could be related to dynamic functions that depend on the timing of action potentials. We stimulated locally connected random networks of spiking neurons and observed the effect of a spike-timing-dependent synaptic plasticity (STDP)-driven pruning process on the emergence of cell assemblies. The spike trains of the simulated excitatory neurons were recorded. We searched for spatiotemporal firing patterns as potential markers of the build-up of functionally organized recurrent activity associated with spatially organized connectivity.


Tirzepatide reduces the predicted risk of atherosclerotic cardiovascular disease and improves cardiometabolic risk factors in adults with obesity or overweight: SURMOUNT-1 post hoc analysis.
To assess the effect of tirzepatide on long-term risk of atherosclerotic cardiovascular disease (ASCVD) among people with obesity or overweight without diabetes from SURMOUNT-1. SURMOUNT-1, a phase 3 trial, evaluated the efficacy and safety of tirzepatide in adults with body mass index ≥30 or ≥27 kg/m2 and at least one weight-related complication, excluding diabetes. Participants were randomly assigned to tirzepatide (5/10/15 mg) or placebo. Changes from baseline in cardiometabolic variables were assessed. The predicted 10-year ASCVD risk scores were calculated (American College of Cardiology/American Heart Association risk engine) at baseline, week 24, and week 72 in SURMOUNT-1 participants without a history of ASCVD. Percent change in risk scores from baseline to weeks 24 and 72 was compared between tirzepatide and placebo using mixed model for repeated measures analysis. Analyses were also conducted in participants with intermediate to high risk at baseline. Tirzepatide-treated groups demonstrated reductions in cardiometabolic variables over 72 weeks. In participants without a history of ASCVD (N = 2461), the baseline median risk score was low and did not differ across groups (1.5%-1.6%). Relative change in risk from baseline to week 72 was greater for tirzepatide (-23.5% to -16.4%) than placebo (12.7%; P < 0.001). Relative change among participants with intermediate-to-high baseline risk was significantly greater for tirzepatide (P < 0.05). Intermediate-to-high-risk participants demonstrated similar relative change but greater absolute risk reduction compared to the overall population. Tirzepatide treatment significantly reduced the 10-year predicted risk of ASCVD versus placebo in patients with obesity or overweight without diabetes.


Multisorbent plasma perfusion in fulminant hepatic failure: effects of duration and frequency of treatment in rats with grade III hepatic coma.
Using the model of galactosamine-induced fulminant hepatic failure in the rat, the effects of multisorbent plasma perfusion over Asahi uncoated spherical charcoal, Plasorba (BR-350) resin, and an endotoxin removing adsorbent (polymyxin B-sepharose) were determined in Grade III hepatic coma animals by studying survival as influenced by timing, duration, and frequency of treatment. The effects of treatment on liver cell proliferation and endotoxin removal also were examined. The results demonstrate that duration and frequency of treatment are major contributing factors in the successful application of nonbiological membrane-based multisorbent liver support systems. Examination of the regenerative activity in the liver indicates an enhanced proliferative response following multisorbent plasma perfusion compared with untreated fulminant hepatic failure (FHF) paired controls. Utilizing an endotoxin removal adsorbent alone, a marked reduction in systemic levels of endotoxin in FHF was demonstrated compared with nonperfused FHF paired controls. Despite current emphasis on bioartificial liver support systems, plasma purification by multisorbent systems offers a simple method for the removal of circulating toxic metabolites in general together with specific toxin removal.


Molecular cloning and expression of canine hepcidin.
Hepcidin is a recently identified acute phase protein with antimicrobial and iron regulatory functions. It has been suggested that hepcidin may be the key mediator of anemia of chronic disease. Our research group is interested in developing a diagnostic assay to measure hepcidin in dogs. The objectives of this study were to clone and sequence the canine hepcidin gene and to gather preliminary data about tissue expression of hepcidin in dogs. RNA was extracted from fresh canine liver tissue and cDNA was generated and amplified. Standard reverse transcription polymerase chain reaction techniques were used with degenerate primers based on sequence homology between several other species. The amino acid (AA) sequence was compared with known sequences in other species. Tissue expression of canine hepcidin was determined by Western blot. The canine hepcidin cDNA sequence encoded a highly conserved protein of 85 AAs with 8 cysteine residues at the C-terminal end. This protein was likely the precursor form (pro-hepcidin) of a smaller secreted peptide. Phylogenetic analysis showed that human hepcidin was more homologous with canine than with rodent hepcidin. In dogs, as in people, hepcidin was expressed most strongly in the liver. Western blotting showed a clear band of approximately 9 kDa, consistent with pro-hepcidin. Weak expression was also detected in canine kidney and lung tissues. The results of this study establish the basis for future investigation involving canine hepcidin and suggest that the dog may be a suitable model for studying the role of hepcidin in human health and disease.


Anticoagulation risk in spine surgery.
Systematic review. To determine the high-risk populations for thromboembolic events in spine surgery patients, the risk of anticoagulation in spine surgery patients by type of anticoagulation, and whether there is a safe perioperative window of nonanticoagulation for these high-risk patients. Thromboembolic complications after major spinal surgery is a significant risk for patients. Anticoagulation to reduce this risk is of concern because of the possibility of excessive bleeding or postoperative hematomas and associated neurologic deficits. There seems to be a paucity of literature on this topic. A systematic review of the English-language literature was undertaken for articles published between January 1990 and December 2008. Electronic databases and reference lists of key articles were searched to identify published studies examining coagulopathy in major spine surgery. Two independent reviewers assessed the strength of literature using the Grading of Recommendations Assessment, Development, and Evaluation criteria, assessing quality, quantity, and consistency of results. Disagreements were resolved by consensus. A total of 93 articles were initially screened, and 29 ultimately met the predetermined inclusion criteria. The risk of thromboembolism in patients not receiving chemical prophylaxis was slightly higher in surgery to correct deformity (5.3%) and trauma patients (6.0%) than in surgery for degenerative conditions (2.3%). Fatal pulmonary embolism was rare. Bleeding complications occurred rarely with the use of anticoagulation; risk of major bleeding ranged from 0.0% to 4.3% across several types of anticoagulants. Postoperative hematoma was reported in only 10 of 2507 patients. Venous thromboembolism is uncommon after elective spine surgery. Trauma patients are at increased risk, and chemical prophylaxis should be considered. The safe timing of the administration of anticoagulation agents is unknown.


Concurrent deficits of soleus and gastrocnemius muscle fascicles and Achilles tendon post stroke.
Calf muscles and Achilles tendon play important roles in functional activities. However, it is not clear how biomechanical properties of the uniarticular soleus (SOL) and biarticular gastrocnemius muscle and Achilles tendon, including the fascicle length, pennation angle, and stiffness, change concurrently post stroke. Biomechanical properties of the medial gastrocnemius (GM) and soleus muscles were evaluated bilaterally in 10 hemiparetic stroke survivors using combined ultrasonography-biomechanical measurements. Biomechanical properties of the Achilles tendon including the length, cross-sectional area (CSA), stiffness, and Young's modulus were evaluated, together with calf muscle biomechanical properties. Gastrocnemius and SOL contributions were separated using flexed and extended knee positions. The impaired side showed decreased fascicle length (GM: 6%, P = 0.002 and SOL: 9%, P = 0.03, at full knee extension and 0° ankle dorsiflexion) and increased fascicular stiffness (GM: 64%, P = 0.005 and SOL: 19%, P = 0.012, at a common 50 N force level). In contrast, Achilles tendon on the impaired side showed changes in the opposite direction as the muscle fascicles with increased tendon length (5%, P < 0.001), decreased tendon CSA (5%, P = 0.04), decreased tendon stiffness (42%, P < 0.001) and Young's modulus (30%, P < 0.001) compared with the unimpaired side. The fascicle and tendon stiffness changes were correlated negatively to the corresponding fascicle and tendon length changes, and decrease in Achilles tendon stiffness was correlated to the increases of SOL and GM fascicular stiffness (P < 0.05). Characterizations of calf muscle fascicles and Achilles tendon biomechanical properties help us better understand concurrent changes of fascicles and tendon as part of the calf muscle-tendon unit and facilitate development of more effective treatments.


Sweating and skin blood flow during exercise: effects of age and maximal oxygen uptake.
Individuals greater than or equal to 60 yr of age are more susceptible to hyperthermia than younger people. However, the mechanisms involved remain unclear. To gain further insight, we examined the heat loss responses of 7 young (24-30 yr) and 13 older (58-74 yr) men during 20 min of cycle exercise [67.5% maximal O2 uptake (VO2max)] in a warm environment (30 degrees C, 55% relative humidity). Forearm blood flow (FBF) and chest sweat rate (SR) were plotted as a function of the weighted average of mean skin and esophageal temperatures [Tes(w)] during exercise. The sensitivity and threshold for each response were defined as the slope and Tes(w) at the onset of the response, respectively. When the young sedentary men were compared with a subgroup (n = 7) of the older physically active men with similar VO2max, the SR and FBF responses of the two groups did not differ significantly. However, when the young men were compared with a subgroup of older sedentary men with a similar maximal O2 pulse, the SR and FBF sensitivities were significantly reduced by 62 and 40%, respectively. These findings suggest that during a short exercise bout either 1) there is no primary effect of aging on heat loss responses but, rather, changes are associated with the age-related decrease in VO2max or 2) the decline in heat loss responses due to aging may be masked by repeated exercise training.


A Facilitated Peer Mentoring Program With a Dedicated Curriculum to Foster Career Advancement of Academic Hospitalists.
In the field of hospital medicine, there is both a limited pool of senior faculty to mentor the rapidly growing number of junior faculty and a lack of career development curricula focused on scholarly activities specific to the needs of the hospitalist. These deficits have resulted in a disproportionately low number of academic hospitalists being promoted to associate and full professor. We implemented a facilitated peer mentoring program with a dedicated curriculum to foster career advancement of academic hospitalists. We recruited 29 academic hospitalists and divided them into five small groups, each guided by one senior faculty. Peer members participated in a 9-month curriculum consisting of alternating large- and small-group sessions that reviewed topics important for academic advancement. Quantitative analysis assessed feasibility of the program, as measured by participation and knowledge improvement on curriculum topics, with pre- and postprogram surveys. Results demonstrated feasibility of the large-group sessions as measured through participation. Small-group participation was more variable. Pre- and postsurvey results showed significant knowledge improvement (p < .05) in nearly all of the curriculum topics. Currently, there is a gap in both mentorship and scholarly skills of academic hospitalists. Our facilitated peer mentoring program with a dedicated curriculum can be used as a framework for other hospitalist programs to support career development.


[Features and mechanisms of the effect of adrenaline and noradrenaline on the pumping function of the heart during hypokinesia].
The effect of epinephrine (E) and norepinephrine (NE) on cardiac output (CO) and heart rate (HR) of hypokinetic and control rats was studied. It was found that in the hypokinetic animals the E effect on CO was significantly weaker than in the controls while the NE effect was stronger. In most experiments the response to NE in the hypokinetic animals was greater than that to E. The mean HR increase was not significantly different in the two groups but in the hypokinetic rats the response to E was less expressed. These data give reason to believe that the lower E effect on CO in the hypokinetic animals is associated with diminished alpha-adrenergic effects on the heart.


In-Flight Management of a Supraventricular Tachycardia Using Telemedicine.
Supraventricular tachycardia (SVT) is a common presenting arrhythmia in the general population. Cases of SVT presenting during commercial air travel are always challenging as they might be confused with other conditions requiring different treatment strategies. We present a case of an in-flight SVT that was successfully managed using telemedicine support. A 33-yr-old woman developed chest pain and dizziness while on an international commercial flight. Vital signs obtained on an on-board telemedicine device recorded an initial heart rate and blood pressure of 220 bpm and 128/78 mmHg, respectively. An electrocardiogram (ECG) was also obtained and transmitted to the ground-based medical support (GBMS) center where an SVT was diagnosed. Vagal maneuvers were recommended which resulted in a return to sinus rhythm and stabilization of the patient. In parallel to the global increase in commercial air travel, it is expected that the incidence of in-flight arrhythmias will also increase, including SVTs. Vagal maneuvers are a safe, first-line option. While treating patients with a symptomatic tachyarrhythmia it is essential to diagnose the underlying arrhythmia, especially when initial maneuvers fail. Telemedicine, with transmission of vital signs and ECGs to GBMS centers, can enable diagnosis and guide management of in-flight SVTs, distinguishing them from other forms of cardiac arrhythmia. Undifferentiated chest pain and dizziness are common causes for flight diversions and, as such, could potentially be prevented in some instances by using telemedicine.Voerman JJ, Hoffe ME, Surka S, Alves PM. In-flight management of a supraventricular tachycardia using telemedicine. Aerosp Med Hum Perform. 2018; 89(7):657-660.


Decreased otolith-mediated vestibular response in 25 astronauts induced by long-duration spaceflight.
The information coming from the vestibular otolith organs is important for the brain when reflexively making appropriate visual and spinal corrections to maintain balance. Symptoms related to failed balance control and navigation are commonly observed in astronauts returning from space. To investigate the effect of microgravity exposure on the otoliths, we studied the otolith-mediated responses elicited by centrifugation in a group of 25 astronauts before and after 6 mo of spaceflight. Ocular counterrolling (OCR) is an otolith-driven reflex that is sensitive to head tilt with regard to gravity and tilts of the gravito-inertial acceleration vector during centrifugation. When comparing pre- and postflight OCR, we found a statistically significant decrease of the OCR response upon return. Nine days after return, the OCR was back at preflight level, indicating a full recovery. Our large study sample allows for more general physiological conclusions about the effect of prolonged microgravity on the otolith system. A deconditioned otolith system is thought to be the cause of several of the negative effects seen in returning astronauts, such as spatial disorientation and orthostatic intolerance. This knowledge should be taken into account for future long-term space missions.