Fluticasone furoate nasal spray is effective and well tolerated for perennial allergic rhinitis in adolescents and adults.
Fluticasone furoate nasal spray (FFNS), an intranasal corticosteroid, has been shown to be effective in perennial allergic rhinitis in randomized, double-blind, placebo-controlled studies but has been less extensively studied in perennial allergic rhinitis than seasonal allergic rhinitis. This study was designed to evaluate the efficacy and safety of FFNS in perennial allergic rhinitis in adolescents and adults ≥12 years of age. In this randomized, double-blind, placebo-controlled, parallel-group study (FFU111439), patients ≥12 years old with perennial allergic rhinitis received FFNS, 110 micrograms (n = 160), or placebo (n = 155) q.d. for 4 weeks. Over the entire treatment period, FFNS was significantly (p < 0.05) more effective than placebo with respect to mean changes from baseline in daily reflective total nasal symptoms (primary end point), morning and evening reflective total nasal symptoms, daily reflective individual nasal symptoms, morning predose instantaneous total and individual nasal symptoms, and morning and evening peak nasal inspiratory flow. FFNS did not show a statistically significant difference from placebo in comparisons of ocular symptom measures. Clinically meaningful improvement versus placebo was observed on the Rhinoconjunctivitis Quality of Life Questionnaire with Standardised Activities overall score. Adverse events reported in >3% of patients in a treatment group and reported more frequently with FFNS than placebo were epistaxis (15% FFNS, 8% placebo) and nasopharyngitis (5% FFNS, 1% placebo). Once-daily FFNS was well tolerated and more effective than placebo at improving nasal symptoms of perennial allergic rhinitis in adolescents and adults ≥12 years of age.


Pushing the limits of sensitivity and resolution for natural abundance 43Ca NMR using ultra-high magnetic field (35.2 T).
Natural abundance 43Ca solid state NMR experiments are reported for the first time at ultra-high magnetic field (35.2 T) on a series of Ca-(pyro)phosphate and Ca-oxalate materials, which are of biological relevance in relation to biomineralization processes and the formation of pathological calcifications. The significant gain in both sensitivity and resolution at 35.2 T leads to unprecedented insight into the structure of both crystalline and amorphous phases.


Sildenafil in Infants and Children.
Pulmonary arterial hypertension (PAH) management has been transformed in recent times with the advent of cheap and effective diagnostic tools and therapy. Sildenafil, a phosphodiesterase-V inhibitor, has been at the centre of this treatment, and its success in treating PAH has led to its widespread uptake in adult and paediatric pulmonary hypertension (PH), as a first line treatment choice. This might apply to persistent pulmonary hypertension of the newborn (PPHN) or bronchopulmonary dysplasia, as well as to more complex diseases, such as idiopathic pulmonary hypertension. Although recent data regarding long-term mortality and the repeal of Food and Drug Administration (FDA) approval has complicated the issue, Sildenafil continues to be the major treatment option for paediatric PH for patients in a variety of contexts, and this does not seem likely to change in the foreseeable future. In this review, we provide a summary of pulmonary hypertension in infants and children and the use of Sildenafil for such diseases.


The Use of TNFα Inhibitors in Treating Pediatric Skin Disorders.
Tumor necrosis factor alpha (TNF) inhibitors have had a significant impact in medicine since the approval of the first drug of its class by the US FDA in 1998. New clinical data and indications have emerged for TNF inhibitors in recent years. Currently, four TNF inhibitors have been approved by the US FDA for dermatology, two of which include US FDA-approved pediatric use. In particular, growing evidence supports the use of etanercept and adalimumab as attractive therapies for pediatric psoriasis. Data for use of etanercept in treating toxic epidermal necrolysis and either etanercept or infliximab for Kawasaki disease is expanding. In addition, there have been clinical reports on the use of TNF inhibitors to treat a variety of other pediatric dermatologic conditions. To help clinicians keep pace with the new data provided by many pediatric dermatology studies involving TNF inhibitors, this review provides an overview of the use of TNF inhibitors in the treatment of pediatric plaque psoriasis, hidradenitis suppurativa, atopic dermatitis, pyoderma gangrenosum, toxic epidermal necrolysis, and Kawasaki disease. For TNF inhibitors with little data in the pediatric population, data on adult use is discussed. Furthermore, the review summarizes available clinical data on efficacy, safety, and tolerability of agents currently available.


Oral buflomedil in diabetic background retinopathy: results of a preliminary controlled study.
Twenty insulin-dependent diabetic patients with signs of background retinopathy were given Buflomedil 600 mg/day orally or placebo in a randomized double-blind trial for a 6-month period. A larger number of patients had their retinal condition deteriorating in the placebo group and this finding is an indication for pursuing investigations on a larger scale in this direction.


A gastroschisis-like abdominal wall defect in the left hypochondrium. Case report and literature review.
Congenital abdominal wall defects are exceedingly rare on the left side. The presented patient had an upper abdominal wall defect located just lateral to the left rectus muscle. Additionally, upper parts of the abdominal flat muscles were defective on that side. Because no report was found in the literature about the defect described here, both its terminological and embryological backgrounds are discussed.


[Serial measurements of serum carcinoembryonic antigen (CEA) and neuron-specific enolase (NSE) during chemotherapy of patients with inoperable lung cancer].
Serial measurements of serum CEA levels were analyzed in 226 patients with inoperable lung cancer (115 small cell carcinomas, 64 adenocarcinomas, 37 squamous cell carcinomas and 10 large cell carcinomas) during chemotherapy. Of all patients, 29.1% had pretreatment CEA levels greater than or equal to 5 ng/ml. In all of the patients with complete response, and 15 (68.2%) of 22 patients with partial response whose pretreatment CEA levels were 5 ng/ml or higher, CEA levels fell to below 5 ng/ml. All of 17 patients who showed a decrease greater than 50% in serum CEA levels during chemotherapy showed a shrinkage of more than 50% in the tumor burden. Serial serum CEA level measurements were useful as an indicator of response to chemotherapy in advanced lung cancer. Serial serum NSE levels were measured in 36 patients with small cell lung cancer. Pretreatment NSE levels were elevated to more than 10 ng/ml in 83.1% of all patients. A transient rise in serum NSE levels occurred in 22 out of 33 patients measured on the third day during initial chemotherapy. Serum NSE levels greater than or equal to 10 ng/ml declined to within the normal range in all patients responding to the chemotherapy. The survival in patients whose NSE levels (greater than or equal to 10 ng/ml) fell to within the normal range for more than four weeks was longer than that in other patients. Serial measurements of serum NSE levels were thus useful for monitoring the response to chemotherapy in cases of small cell lung cancer.


Focal therapy and imaging in prostate and kidney cancer: high-intensity focused ultrasound ablation of small renal tumors.
The rising incidence of small, incidentally detected renal masses in elderly, infirm patients has raised interest in minimally invasive, energy ablative techniques. High-intensity focused ultrasound (HIFU) delivers ultrasonic energy, resulting in heat and tissue destruction in the targeted tissue at a selected depth. In contrast to radiofrequency ablation and cryoablation, HIFU does not require puncturing the tumor, avoiding the high risk of hemorrhage or tumor spillage. While the extracorporeal approach shows unsatisfactory results, laparoscopic HIFU appears to be a promising alternative treatment option. Problems with respiratory movement and interphases, as seen in extracorporeal HIFU, are avoided when the transducer is brought directly to the target by laparoscopic HIFU. Potential benefits of laparoscopic HIFU are decreased morbidity, shorter hospitalization and convalescence, and preservation of renal function. Nevertheless, further prospective studies have to be performed to define the oncological success of HIFU as an alternative to open and laparoscopic surgery in small renal masses.


Screening for cryptococcal antigenemia in anti-retroviral naïve AIDS patients in benin city, Nigeria.
Cryptococcus neoformans is the most incriminated fungal pathogen causing meningitis in acquired immune deficiency syndrome (AIDS) patients, and is known to constitute a major cause of deaths in AIDS patients. This study thus aimed to determine the baseline sero-prevalence of Cryptococcus neoformans infection in anti-retroviral naïve (ART-naïve) AIDS patients using the serum Cryptococcal antigen (crag) detection method. Baseline effect of variation in CD4 counts, as well as sex and age with sero-positivity for crag were also determined. This descriptive cross-sectional study included 150 (61 males and 89 females) ART-naïve AIDS patients attending the Human Immunodeficiency Virus clinic (HIV) at the University of Benin Teaching hospital, Benin City, Nigeria, within the period from February 2011- July 2011. Forty (18 males and 22 females) HIV positive outpatients with CD4 counts >200 cells/µl who were ART-naive were recruited and used as controls. The sero-prevalence of crag in the patients and the control group was measured using the cryptococcal antigen latex agglutination system (CALAS) (Meridian Bioscience, Europe) and CD4 counts were measured using flow cytometry (Partec flow cytometer, Germany). Of the 150 ART-naïve AIDS patients with CD4 counts ≤200 cells/µL; 19 (12.7%) were positive for serum Cryptococcal antigen. ART-naïve AIDS patients with CD4 count ≤50 cells/µl had the highest prevalence of serum crag. Lower CD4 counts were significantly associated with positivity for serum crag (p<0.001). Age and sex had no significant effect on the sero-positivity for serum crag. One (2.5%) of the controls was sero-positive for crag. Thus, serum crag was significantly associated with AIDS but not with HIV (p<0.001). This study uncovers a high prevalence of crag in ART- naïve AIDS patients in Benin City. The prevalence of crag was higher in ART-naïve AIDS patients with lower CD4 counts. There is an urgent need to introduce routine screening for crag in ART- naïve AIDS patients in our locality to reduce the rapid mortality from Cryptococcal meningitis which accounts for a majority of the morbidity factor if undiagnosed during ART therapy.


Bevacizumab promotes active biological behaviors of human umbilical vein endothelial cells by activating TGFβ1 pathways via off-VEGF signaling.
Objective: Bevacizumab is a recombinant humanized monoclonal antibody that blocks vascular endothelial growth factor (VEGF) with clear clinical benefits. However, overall survival of some cancer types remains low owing to resistance to bevacizumab therapy. While resistance is commonly ascribed to tumor cell invasion induced by hypoxia-inducible factor (HIF), less attention has been paid to the potential involvement of endothelial cells (ECs) in vasculature activated by anti-angiogenic drugs. Methods: Human umbilical vein ECs (HUVECs), bEnd.3 cells, and mouse retinal microvascular ECs (MRMECs) were treated with bevacizumab under conditions of hypoxia and effects on biological behaviors, such as migration and tube formation, examined. Regulatory effects on TGFβ1 and CD105 (endoglin) were established via determination of protein and mRNA levels. We further investigated whether the effects of bevacizumab could be reversed using the receptor tyrosine kinase inhibitor anlotinib. Results: Bevacizumab upregulated TGFβ1 as well as CD105, a component of the TGFβ receptor complex and an angiogenesis promoter. Elevated CD105 induced activation of Smad1/5, the inflammatory pathway and endothelial-mesenchymal transition. The migration ability of HUVECs was enhanced by bevacizumab under hypoxia. Upregulation of CD105 was abrogated by anlotinib, which targets multiple receptor tyrosine kinases including VEGFR2/3, FGFR1-4, PDGFRα/β, C-Kit, and RET. Conclusions: Bevacizumab promotes migration and tube formation of HUVECs via activation of the TGFβ1 pathway and upregulation of CD105 expression. Anlotinib reverses the effects of bevacizumab by inhibiting the above signals.


Aminothienopyridazines and methylene blue affect Tau fibrillization via cysteine oxidation.
Alzheimer disease and several other neurodegenerative disorders are characterized by the accumulation of intraneuronal fibrils comprised of the protein Tau. Tau is normally a soluble protein that stabilizes microtubules, with splice isoforms that contain either three (3-R) or four (4-R) microtubule binding repeats. The formation of Tau fibrils is thought to result in neuronal damage, and inhibitors of Tau fibrillization may hold promise as therapeutic agents. The process of Tau fibrillization can be replicated in vitro, and a number of small molecules have been identified that inhibit Tau fibril formation. However, little is known about how these molecules affect Tau fibrillization. Here, we examined the mechanism by which the previously described aminothieno pyridazine (ATPZ) series of compounds inhibit Tau fibrillization. Active ATPZs were found to promote the oxidation of the two cysteine residues within 4-R Tau by a redox cycling mechanism, resulting in the formation of a disulfide-containing compact monomer that was refractory to fibrillization. Moreover, the ATPZs facilitated intermolecular disulfide formation between 3-R Tau monomers, leading to dimers that were capable of fibrillization. The ATPZs also caused cysteine oxidation in molecules unrelated to Tau. Interestingly, methylene blue, an inhibitor of Tau fibrillization under evaluation in Alzheimer disease clinical trials, caused a similar oxidation of cysteines in Tau and other molecules. These findings reveal that the ATPZs and methylene blue act by a mechanism that may affect their viability as potential therapeutic agents.


Physiologically high concentrations of 17beta-estradiol enhance NF-kappaB activity in human T cells.
Estrogen has diverse effects on inflammation and immune responses. That pregnancy is associated with remission of some autoimmune diseases and exacerbation of others suggests that physiological fluctuation in estrogen levels could affect the immune responses in humans. However, the molecular basis for these phenomena is poorly understood. We hypothesized that fluctuations of estrogen levels modulate intracellular signaling for immune responses via estrogen receptors (ERs). In reporter assays, 17beta-estradiol (E2) at a physiologically high concentration increased the activity of NF-kappaB in Jurkat cells stimulated by PMA/ionomycin or TNF-alpha. Overexpression and RNA interference experiments suggested that the effects were mediated through ERbeta. Immunoprecipitation assay showed that both ERalpha and ERbeta are directly associated with NF-kappaB in the cell nucleus. Using chromatin immunoprecipitation assay, we confirmed that ERalpha and ERbeta associated with NF-kappaB and steroid hormone coactivators at the promoter region of NF-kappaB regulated gene. Considering that NF-kappaB regulates the expression of various genes essential for cell growth and death, estrogen could regulate the fate of T cells by affecting the activity of NF-kappaB. To determine whether E2 alters the fate of T cells, we investigated E2 actions on T cell apoptosis, a well-known NF-kappaB-mediated phenomenon. E2 increased apoptosis of Jurkat cells and decreased that of human peripheral blood T cells. Our results indicate that E2 at a physiologically high concentration modulates NF-kappaB signaling in human T cells via ERbeta and affects T cell survival, suggesting that these actions may underlie the gender differences in autoimmune diseases.


Birth palsy: natural recovery course and combined root avulsion.
Seventy-six patients with birth palsy were reviewed for type of palsy and mode of delivery. High incidences of root avulsion associated with lesser birth weight were identified in patients of breech deliveries. In 15 patients with serial neurological assessment for more than 5 years, the natural recovery course was evaluated, based on the assessment of particular key muscle and dermatomes mainly innervated by single nerve roots. Rapid and useful motor recovery was observed in upper-type palsy and the upper root levels (C5 and C6) of whole-type palsy, while poor prognosis of motor function was demonstrated in the lower root levels (C8 and D1) of whole-type palsy. Recovery of sensory function was far more predominant than recovery of motor function. Of 12 patients with root avulsion, 10 patients (27 avulsed roots) over 5 years of age were neurologically assessed. Of avulsed roots, 70.4% had useful sensory recovery and 33.3% had useful motor recovery. The patho-mechanism of those with a good prognosis in root avulsion of birth palsy is discussed, based on the findings of this series.


A new dirivultid copepod (Siphonostomatoida) from hydrothermal vent fields of the Izu-Bonin Arc in the North Pacific Ocean.
A new species of dirivultid copepod (Siphonostomatoida) is described from hydrothermal vents in a volcanic seamount in Izu-Bonin Arc, western part of North Pacific Ocean. The copepod was collected during the research cruise NT13-09 using the R/V Natsushima with the ROV Hyper-Dolphin in April 2013. The type series of the new species was collected from the populations of Paralvinella spp. (Annelida: Alvinellidae) on an active vent chimney at the depth of 795 m. Stygiopontius senokuchiae n. sp. is most closely related to S. teres Humes, 1996 but clearly distinguished from the latter species by the possession of the following characters: the basis of leg 1 with an attenuated inner process; the genital double somite with a conical process lateral to the genital opening; and caudal rami without distal process. The findings of the copepod in the present study represents the first record of nominal species of the Dirivultidae from Japanese waters and a record of the shallowest depth of the genus. A key to species of the genus Stygiopontius from Western Pacific is provided.


Selection bias in gene extraction on the basis of microarray gene-expression data.
In the context of cancer diagnosis and treatment, we consider the problem of constructing an accurate prediction rule on the basis of a relatively small number of tumor tissue samples of known type containing the expression data on very many (possibly thousands) genes. Recently, results have been presented in the literature suggesting that it is possible to construct a prediction rule from only a few genes such that it has a negligible prediction error rate. However, in these results the test error or the leave-one-out cross-validated error is calculated without allowance for the selection bias. There is no allowance because the rule is either tested on tissue samples that were used in the first instance to select the genes being used in the rule or because the cross-validation of the rule is not external to the selection process; that is, gene selection is not performed in training the rule at each stage of the cross-validation process. We describe how in practice the selection bias can be assessed and corrected for by either performing a cross-validation or applying the bootstrap external to the selection process. We recommend using 10-fold rather than leave-one-out cross-validation, and concerning the bootstrap, we suggest using the so-called .632+ bootstrap error estimate designed to handle overfitted prediction rules. Using two published data sets, we demonstrate that when correction is made for the selection bias, the cross-validated error is no longer zero for a subset of only a few genes.


Association of AGTR1 A1166C and CYP2C9∗3 Gene Polymorphisms with the Antihypertensive Effect of Valsartan.
The differences in the antihypertensive treatment with angiotensin type II receptor blockers (ARBs) may be attributed to polymorphisms in genes involving drug-targeted receptor and drug metabolism. The present study aimed to investigate whether the antihypertensive effect of the ARB drug valsartan was associated with angiotensin II type 1 receptor (AGTR1) gene polymorphism (A1166 C) and cytochrome P450 enzyme 2C9 (CYP2C9) gene polymorphism (CYP2C9∗3). 281 patients with hypertension who received valsartan monotherapy in the past month were included in this retrospective study. Polymerase chain reaction-melting curve analysis was performed to genotype the AGTR1 and CYP2C9 gene polymorphisms. Based on the systolic blood pressure (SBP) and diastolic blood pressure (DBP) at the time of visit, the patients were divided into well-controlled group (n = 144, SBP/DBP <140/90 mmHg) and poorly controlled group (n = 137, SBP/DBP ≥140/90 mmHg). Older age, decreased history of drinking, a higher proportion of mild-to-moderate hypertension, lower alanine aminotransferase levels, and higher high-density lipoprotein cholesterol levels were observed in the well-controlled group than the poorly controlled group. Higher frequencies of the C allele and AC + CC genotype of AGTR1 A1166C were detected in the well-controlled than the poorly controlled patients (P = 0.005 and P = 0.006). After adjustment for demographic and environmental factors, the CC + AC genotype of AGTR1 A1166C was markedly linked to better hypertension control with valsartan treatment compared to the AA genotype (odds ratio: 2.836, 95% confidence interval: 1.199-6.705, P = 0.018). No significant difference was observed in the allele or genotype distribution of CYP2C9∗3 polymorphism between well-controlled and poorly controlled patients. The current data suggested that the AGTR1 A1166 C polymorphism may be associated with the antihypertensive effect of valsartan, and carriers with AC and CC genotypes may have a better antihypertensive efficacy response to valsartan treatment.


Piezo1 channel activation facilitates baroreflex afferent neurotransmission with subsequent blood pressure reduction in control and hypertension rats.
Mechanosensitive cation channels such as Piezo1 and Piezo2 are activated by mechanical force like a starched wall of the aorta while blood pressure (BP) rising, which helps to elucidate the underlying mechanism of mechanotransduction of baroreceptor endings. In this study we investigated how Piezo1 channel activation-mediated gender- and afferent-specific BP regulation in rats. We established high-fat diet and fructose drink-induced hypertension model rats (HFD-HTN) and deoxycorticosterone (DOCA)-sensitive hypertension model rats. We showed that the expression levels of Piezo1 and Piezo2 were significantly up-regulated in left ventricle of HFD and DOCA hypertensive rats, whereas the down-regulation of Piezo1 was likely to be compensated by Piezo2 up-regulation in the aorta. Likewise, down-regulated Piezo1 was observed in the nodose ganglion (NG), while up-regulated Piezo2 was found in the nucleus tractus solitarius (NTS), which might synergistically reduce the excitatory neurotransmitter release from the presynaptic membrane. Notably, microinjection of Yoda1 (0.025-2.5 mg/ml) into the NG concentration-dependently reduced BP in both hypertensive rat models as well as in control rats with similar EC50; the effect of Yoda1 was abolished by microinjection of a Piezo1 antagonist GsMTx4 (1.0 μM). Functional analysis in an in vitro aortic arch preparation showed that instantaneous firing frequency of single Ah-fiber of aortic depressor nerve was dramatically increased by Yoda1 (0.03-1.0 μM) and blocked by GsMTx4 (1.0 μM). Moreover, spontaneous synaptic currents recorded from identified 2nd-order Ah-type baroreceptive neurons in the NTS was also facilitated over 100% by Yoda1 (1.0 μM) and completely blocked by GsMTx4 (3.0 μM). These results demonstrate that Piezo1 expressed on Ah-type baroreceptor and baroreceptive neurons in the NG and NTS plays a key role in a sexual-dimorphic BP regulation under physiological and hypertensive condition through facilitation of baroreflex afferent neurotransmission, which is presumably collaborated by Piezo2 expression at different level of baroreflex afferent pathway via compensatory and synergistic mechanisms.


Sexuality of midlife and older women: A review of theory use.
Sexual experiences of older adults remain underexplored. This review examined 21 articles focused on the sexuality of midlife and older women to identify theories used and understand how theory informs this literature. Reviewed articles described a dominant narrative of sexual decline in later life but positioned their own work as counternarratives. A majority applied social constructionist, critical, or interpretivist orientations, balancing material and socially constructed aspects of sexuality. Theories were most likely to inform the purpose and conclusions and least likely to inform limitations or descriptions of study samples. Findings support the need to affirm diverse sexual experiences of women.


Note: The effect of sample insulation on experiment precision of resistivity measurement in a diamond anvil cell.
By use of electrical field analysis method, the accuracy of electrical resistivity measurement with the van der Pauw method in a diamond anvil cell (DAC) was investigated for the situation that sample and gasket were electrically shorted. It is revealed that metal gasket could not be used in electrical measurement in DAC if the inside wall of the sample chamber was not insulated. When the shorted area was less than 20% of the inside wall of the sample chamber, the relative error was smaller than 10%. Once the shorted area exceeded 25%, the relative error increased rapidly.


Species distribution and antifungal susceptibilities of bloodstream Candida isolates: a nine-years single center survey.
This study analyzed the epidemiology of bloodstream infections due to Candida spp. in a tertiary referral hospital of Ancona, Italy, and their susceptibility to antifungals. The retrospective observational study from January 2010 to December 2018 identified 504 episodes of candidemia in 461 patients. Although Candida albicans remained the species most frequently isolated, Candida spp. other than C. albicans caused 49% of the overall episodes of candidemia. According to CLSI interpretation, most of the isolates resulted susceptible to antifungals. Azoles vs Candida tropicalis represented an exception. Echinocandin non-susceptibility was rare across the species. In conclusion, with the exception of C. tropicalis, the isolation of a non-susceptible Candida strains against azoles, echinocandins and amphotericin B was a rare event.


Outcomes.
Outcomes encompass multiple factors, not just success and failure. They include other considerations such as being workable and profitable to the dentist and safe and acceptable to the patient. The more biological outcomes are most frequently measured. These measurements are on a scale from least to most predictable outcomes of treatment by the dentist, as shown on the evidence pyramid. Impact trauma is an example of a general scarcity of high-level evidence with treatment because of the nature and individuality of the injuries and the difficulty (or impossibility) of designing controlled clinical trials in humans. Much of the evidence is cohort (retrospective or observational studies), case reports, animal studies, and "expert" opinion. Thus, guidelines are largely based on lower levels of evidence. Nonetheless, the current guidelines provide the clinician with the best evidence that is available. The best opportunity for randomized controlled trials is in prevention. Specifically, mouthguard design and usage can be subjected to higher levels of controlled research. Revitalization and regeneration are relatively new procedures. To date, there is a lack of high levels of evidence to be able to substantiate whether these are clinically feasible to become a routine in practice.


Immunotherapy of glioblastoma: Recent advances and future prospects.
Glioblastoma (GBM) stands out as the most common, aggressive form of primary malignant brain tumor conferring a devastatingly poor prognosis. Despite aggressive standard-of-care in surgical resection and chemoradiation with temozolomide, the median overall survival of patients still remains no longer than 15 months, due to significant tumor heterogeneity, immunosuppression induced by the tumor immune microenvironment and low mutational burden. Advances in immunotherapeutic approaches have revolutionized the treatment of various cancer types and become conceptually attractive for glioblastoma. In this review, we provide an overview of the basic knowledge underlying immune targeting and promising immunotherapeutic strategies including CAR T cells, oncolytic viruses, cancer vaccines, and checkpoint blockade inhibitors that have been recently investigated in glioblastoma. Current clinical trials and previous clinical trial findings are discussed, shedding light on novel strategies to overcome various limitations and challenges.


The evolving landscape of neurotoxicity by unconjugated bilirubin: role of glial cells and inflammation.
Unconjugated hyperbilirubinemia is a common condition in the first week of postnatal life. Although generally harmless, some neonates may develop very high levels of unconjugated bilirubin (UCB), which may surpass the protective mechanisms of the brain in preventing UCB accumulation. In this case, both short-term and long-term neurodevelopmental disabilities, such as acute and chronic UCB encephalopathy, known as kernicterus, or more subtle alterations defined as bilirubin-induced neurological dysfunction (BIND) may be produced. There is a tremendous variability in babies' vulnerability toward UCB for reasons not yet explained, but preterm birth, sepsis, hypoxia, and hemolytic disease are comprised as risk factors. Therefore, UCB levels and neurological abnormalities are not strictly correlated. Even nowadays, the mechanisms of UCB neurotoxicity are still unclear, as are specific biomarkers, and little is known about lasting sequelae attributable to hyperbilirubinemia. On autopsy, UCB was shown to be within neurons, neuronal processes, and microglia, and to produce loss of neurons, demyelination, and gliosis. In isolated cell cultures, UCB was shown to impair neuronal arborization and to induce the release of pro-inflammatory cytokines from microglia and astrocytes. However, cell dependent sensitivity to UCB toxicity and the role of each nerve cell type remains not fully understood. This review provides a comprehensive insight into cell susceptibilities and molecular targets of UCB in neurons, astrocytes, and oligodendrocytes, and on phenotypic and functional responses of microglia to UCB. Interplay among glia elements and cross-talk with neurons, with a special emphasis in the UCB-induced immunostimulation, and the role of sepsis in BIND pathogenesis are highlighted. New and interesting data on the anti-inflammatory and antioxidant activities of different pharmacological agents are also presented, as novel and promising additional therapeutic approaches to BIND.


Should national standards for reporting surgical site infections distinguish between primary and revision orthopedic surgeries?
To compare the surgical site infection (SSI) rate after primary total hip arthroplasty with the SSI rate after revision total hip arthroplasty. Retrospective cohort study. Mayo Clinic in Rochester, Minnesota, a referral orthopedic center. All patients undergoing primary total hip arthroplasty or revision total hip arthroplasty during the period from January 1, 2002, through December 31, 2006. We obtained data on total hip arthroplasties from a prospectively maintained institutional surgical database. We reviewed data on SSIs collected prospectively as part of routine infection control surveillance, using the criteria of the Centers for Disease Control and Prevention for the definition of an SSI. We used logistic regression analyses to evaluate differences between the SSI rate after primary total hip arthroplasty and the SSI rate after revision total hip arthroplasty. A total of 5,696 total hip arthroplasties (with type 1 wound classification) were analyzed, of which 1,381 (24%) were revisions. A total of 61 SSIs occurred, resulting in an overall SSI rate of 1.1% for all total hip arthroplasties. When stratified by the National Nosocomial Infection Surveillance (NNIS) risk index, SSI rates were 0.5%, 1.2%, and 1.6% in risk categories 0, 1, and 2, respectively. After controlling for the NNIS risk index, the risk of SSI after revision total hip arthroplasty was twice as high as that after primary total hip arthroplasty (odds ratio, 2.2 [95% confidence interval, 1.3-3.7]). In the analysis restricted to the development of deep incisional or organ space infections, the risk of SSI after revision total hip arthroplasty was nearly 4 times that after primary total hip arthroplasty (odds ratio, 3.9 [95% confidence interval, 2.0-7.6]). Including revision surgeries in the calculation of SSI rates can result in higher infection rates for institutions that perform a larger number of revisions. Taking NNIS risk indices into account does not eliminate this effect. Differences between primary and revision surgeries should be considered in national standards for the reporting of SSIs.


Listeners and readers generalize their experience with word meanings across modalities.
Research has shown that adults' lexical-semantic representations are surprisingly malleable. For instance, the interpretation of ambiguous words (e.g., bark) is influenced by experience such that recently encountered meanings become more readily available (Rodd et al., 2016, 2013). However, the mechanism underlying this word-meaning priming effect remains unclear, and competing accounts make different predictions about the extent to which information about word meanings that is gained within one modality (e.g., speech) is transferred to the other modality (e.g., reading) to aid comprehension. In two Web-based experiments, ambiguous target words were primed with either written or spoken sentences that biased their interpretation toward a subordinate meaning, or were unprimed. About 20 min after the prime exposure, interpretation of these target words was tested by presenting them in either written or spoken form, using word association (Experiment 1, N = 78) and speeded semantic relatedness decisions (Experiment 2, N = 181). Both experiments replicated the auditory unimodal priming effect shown previously (Rodd et al., 2016, 2013) and revealed significant cross-modal priming: primed meanings were retrieved more frequently and swiftly across all primed conditions compared with the unprimed baseline. Furthermore, there were no reliable differences in priming levels between unimodal and cross-modal prime-test conditions. These results indicate that recent experience with ambiguous word meanings can bias the reader's or listener's later interpretation of these words in a modality-general way. We identify possible loci of this effect within the context of models of long-term priming and ambiguity resolution. (PsycINFO Database Record (c) 2018 APA, all rights reserved).


Steroid hormone profiles and body conditions of migrating male humpback whales (Megaptera novaeangliae).
Simultaneous analysis of multiple steroid hormones from remotely obtained blubber biopsies has the potential to concurrently provide information regarding stress and reproductive status from free-swimming cetaceans, while also investigating correlations between hormone concentrations and other health biomarkers. In this study we measured blubber concentration profiles of eight reproductive and adrenal steroid hormones (17α-hydroxy-progesterone, testosterone, androstenedione, progesterone, cortisol, 11-deoxy-corticosterone, oestrone, and oestradiol) together with body condition, as determined by the inverse Adipocyte Index, of 101 male humpback whales. Whales were sampled randomly at two time points, while migrating to and from their northeast Australian breeding grounds, allowing for intra- and inter-seasonal profile analysis. Testosterone, progesterone and cortisol together with androstenedione 17α-hydroxyprogesterone, and oestrone concentrations (the latter quantified for the first time in live biopsied male humpback whales) decreased between the northward and southward migrations. Decreasing testosterone levels during the height of humpback whale conceptions suggests asynchronicity between blubber testosterone levels and the expected peak of male fertility. Statistically significant relationships between levels of certain steroid analytes were observed and appeared to change between the early and late breeding seasons. During the northward migration, testosterone, progesterone, androstenedione, oestrone and 17α-hydroxyprogesterone levels were positively correlated. Cortisol concentrations correlated positively with those of testosterone during the northward migration, but negatively during the southward migration. Androstenedione and testosterone were positively correlated with adiposity during the late breeding season. These hormone-hormone and hormone-adiposity correlations may be reflective of the activation of certain steroid hormone synthesis pathways, or alternatively, of concomitant physiological stimuli. As steroid hormones work in concert, information on multiple steroid hormones is needed to interpret endocrinological status and understand the relationships between these compounds and ancillary health markers. This study provides steroid hormone profiles of wild male humpback whales, as well as the first insight into seasonal male endocrinology as a function of adiposity.


A Dual-Enzyme-Assisted Three-Dimensional DNA Walking Machine Using T4 Polynucleotide Kinase as Activators and Application in Polynucleotide Kinase Assays.
T4 polynucleotide kinase (T4 PNK), an intracellular kinase, catalyzes the phosphorylation of 5'-hydroxyl termini in nucleic acids and plays a crucial role in DNA-related physiological activities. Malfunctioning of PNK is associated with the deregulation of many cellular activities and eventually induces a variety of human diseases. Herein, we report a smart three-dimensional (3D) DNA walking machine using PNK as an effective activator when coupled with the duplex DNA nuclease-assisted cleavage reaction. The 3D DNA tracks benefit from high DNA loading capacity of gold nanoparticles, and the high efficiency of duplex nuclease-mediated cyclic cleavage facilitates the movement of the DNA machine in response to T4 PNK. The DNA machine is also applied for the PNK assay based on the signal amplification from point to area during the DNA walking process. The method achieves an excellent detection limit of 0.0067 U/mL with a linear range from 0.01 to 0.3 U/mL and a favorable specificity even in complex serum samples. Therefore, the 3D DNA machine shows great potential in biochemical and molecular biology studies, drug discovery, and clinic diagnostics.


A national survey of "consumer empowerment" at the state level.
A national survey was conducted to determine the extent of consumer empowerment in the public mental health system. A questionnaire was sent to mental health authorities in all U.S. states and territories asking whether consumer empowerment or responsibility was defined in statutes, regulations, or policies and whether consumers or family members were employed in central or field offices of the authority. A rating scale measured the extent of consumer empowerment, and correlations were examined between this rating and other variables. The survey achieved a 100 percent response rate. Twenty-two states (39 percent) addressed consumer empowerment and 16 (28 percent) consumer responsibility in a statute, regulation, or policy. Twenty-seven states (48 percent) had paid positions for consumers in central offices, and three (5 percent) had such positions for family members. Half the states had paid positions for consumers in field offices, and 12 states (24 percent) had such positions for family members. The extent of a state's consumer empowerment had no relationship to region of the country or the state's mental health budget. A significant positive relationship was found between extent of empowerment and the size of the state's population and the quality of its mental health services. State mental health authorities vary widely in their direct involvement with consumer empowerment. Results indicate that mental health authorities need to make a greater commitment to the achievement of such empowerment if it is to become a meaningful part of government involvement with mental health services.


Tandem mass spectrometry: a convenient approach in the dosage of steviol glycosides in Stevia sweetened commercial food beverages.
The use of sweeteners extracted from leaves of the plant species Stevia rebaudiana is increasing worldwide. They are recognized as generally recognized as safe by the US-FDA and approved by EU-European Food Safety Authority, with some recommendation on the daily dosage that should not interfere with glucose metabolism. The results presented here introduce an easy analytical approach for the identification and assay of Stevia sweeteners in commercially available soft drink, based on liquid chromatography coupled to tandem mass spectrometry, using a natural statin-like molecule, Brutieridin, as internal standard. Copyright © 2017 John Wiley & Sons, Ltd.


Tibial pilon fracture repair using Ilizarov external fixation, capsuloligamentotaxis, and early rehabilitation of the ankle.
Open surgical treatment of comminuted tibial pilon fractures is associated with substantial complications in many patients. Indirect reduction and stabilization of fractures by means of distraction using a circular external fixator can be a useful method of achieving satisfactory joint restoration, and employs the principles of closed reduction to realign disrupted bones and joint structures. In this report, we describe the case of a patient with a comminuted tibial pilon fracture treated by means of closed reduction and stabilization using a circular external fixator.


Factors influencing home death in a Japanese metropolitan region.
To examine factors influencing home death, an anonymous survey was mailed to 998 home care supporting clinics (HCSCs) in the 23 wards of Tokyo, Japan. We classified the HCSCs into two types (single physician practice and multiple physician practice) and identified factors of each type of practice that predict home death. The factors associated with a greater probability of dying at home were as follows: in the multiple physician practices, collaboration with hospitals and teaching coping skills to the family members and, in the single physician practices, collaboration with clinics. Our findings suggest that home end-of-life care services are unlikely to be achieved without cooperation among service providers and without improvement of the family members' coping skills.


[A comparison between three questionnaires and laboratory tests for the detection of alcoholism in general practice].
By means of a case/control study, an attempt was made to identify the different questionnaires and biological tests which might be used in the General Practice consulting room for the detection of alcoholic patients. A comparison was made between the CABE, MALT, and Skinner questionnaires, and the MCV, AST, ALT, GGT triglyceride, cholesterol, uric acid, bilirubin and glycemia biological tests. Sensitivity, specificity, predictive value and diagnostic efficiency were studied in a group of 37 confirmed alcoholics and 25 controls making up a population with a high prevalence of alcoholism. Later we analysed the changes which affect the values of the different tests when applied to a population with a low prevalence of alcoholism, in other words, the utility of the tests in general practice was evaluated. The study concludes that the diagnostic performance of the questionnaires together with case history is higher than that of biological tests in general practice, and that the routine application tests in general practice, and that the routine application of the CAGE questionnaire and to a lesser extent of the Skinner questionnaire make it possible to identify those patients suspected of alcoholism and to improve the predictive value of the biological tests applied thereafter. Nevertheless further study is necessary to confirm the diagnostic effectiveness of these questionnaires in the general population of health centre patients.


[Electron microscopy of the lesions produced in the human dura mater by Quincke beveled and Whitacre needles].
Comparisons of Quincke needles and non traumatic "pencil point" needles in recent years have reported lower rates of post dural puncture headache using the later type. Our new understanding of the morphology of the human dura mater motivated us to study dural lesions caused by the Whitacre 25 G and Quincke 26 G needles, using scanning electron microscopy with the aim of determining whether there is an anatomic basis for the different outcomes. The dura mater from three fresh cadavers of individuals aged 65, 70 and 72 years were punctured 40 times at an angle of 90 degrees each time. The Whitacre 25 G needle was used for 20 punctures and the Quincke 26 G needle was used for the other 20. Half the punctures were performed with the bevel in the parallel alignment and the other half with the bevel perpendicular to the spinal column. Fifteen min after causing the punctures, specimens were fixed in solutions of glutaraldehyde phosphate buffer and dehydrated in acetone. After critical point removal of the acetone, after the specimens were treated with carbon and metallized with gold. The lesions were examined externally and internally and expressed as the ratio of area of lesion to diameter of the needle that had caused them. Whitacre needle: each lesion consisted in the superimposition of multiple damaged layers that started to close individually. After 15 min the outermost layers were 90% closed and the innermost ones had closed entirely. Layers in the arachnoid surface of the dura mater had closed from 86 to 88%, while deeper layers in the thick part had closed 97 to 98%. Quincke needle: lesions were V-shaped or half-moon shaped, much like the opening formed by a can opener, on both the external and internal surfaces. Alignment of the bevel of the needle parallel to the spinal column did not lead to a different shape of puncture. After 15 min the lesions had closed 94 to 95% on the epidural surface and 95 to 96% on the arachnoid side, a difference attributable to the retraction of the arachnoid layers over the spinal column. Non traumatic beveled dural needles, termed "pencil point needles", only partially separate dural fibers, and lesions caused by these needles develop in a more complex way. The Quincke 26G needle produced a puncture that is morphologically different from that caused by the Whitacre 25G needle, although lesions produced by both types close more than 94% after 15 min. We believe the size of the lesion caused by these needles does not explain the difference in post dural puncture headache due to loss of spinal fluid.


Water-Mediated Peptide Bond Formation in the Gas Phase: A Model Prebiotic Reaction.
The emergence of life on the prebiotic Earth must have involved the formation of polypeptides, yet the polymerization of amino acids is thermodynamically unfavorable under biologically relevant aqueous conditions because amino acids are zwitterions in solution and because of the production of a water molecule through a condensation reaction. Many mechanisms for overcoming this thermodynamic unfavorability have been proposed, but the role of gas phase water clusters has not been investigated. We present the thermodynamics of the water-mediated gas phase dimerization reaction of glycine as a model for the atmospheric polymerization of amino acids prior to the emergence of biological machinery. We hypothesize that atmospheric aerosols may have played a major role in the prebiotic formation of peptide bonds by providing the thermodynamic driving force to facilitate increasingly stable linear oligopeptides. In addition, we hypothesize that small aerosols orient amino acids on their surfaces, thus providing the correct molecular orientations to funnel the reaction pathways of peptides through transition states that lead eventually to polypeptide products. Using density functional theory and a thorough configurational sampling technique, we show that the thermodynamic spontaneity of the linear dimerization of glycine in the gas phase can be driven by the addition of individual water molecules.


Prediction of hydrocarbon enthalpies of formation by various thermochemical schemes.
The correlation consistent composite approach (ccCA) has been used to compute the enthalpies of formation (ΔH(f)'s) for 60 closed-shell, neutral hydrocarbon molecules selected from an established set (Cioslowski et al., J. Chem. Phys. 2000, 113, 9377). This set of thermodynamic values includes ΔH(f)'s for hydrocarbons that span a range of molecular sizes, degrees of aromaticity, and geometrical configurations, and, as such, provides a rigorous assessment of ccCA's applicability to a variety of hydrocarbons. The ΔH(f)'s were calculated via atomization energies, isodesmic reactions, and hypohomodesmotic reactions. In addition, for 12 of the aromatic molecules in the set that are larger than benzene, the energies of ring-conserved isodesmic reactions were used to calculate the ΔH(f)'s. Using an atomization energy approach to determine the ΔH(f)'s, the lowest mean absolute deviation (MAD) from experiment achieved by ccCA for the 60 hydrocarbons was 1.10 kcal mol(-1). The use of the mixed Gaussian/inverse exponential complete basis set extrapolation scheme (ccCA-P) in conjunction with hypohomodesmotic reaction energies resulted in a MAD of 0.87 kcal mol(-1). This value is compared with MADs of 1.17, 1.18, and 1.28 kcal mol(-1) obtained via the Gaussian-4 (G4), Gaussian-3 (G3), and Gaussian-3(MP2) [G3(MP2)] methods, respectively (using the hypohomodesmotic reactions).


Family and professional caregivers' ratings of dementia symptoms and activities of daily living of day care patients: do differences change over time?
The purpose of this study was to compare ratings of patients' carried out by professional and family caregivers. These patients were attending rehabilitative geriatric and gerontopsychiatric day care centres, they were about 77 years old, 93% had dementia, and each had an average of 4.7 diseases. Eighty percent of the family caregivers were female, and 60% were children of the patients. Staff raters of the day care units were trained professionals. Data were collected at two measurement times: T1 took place during the first ten days of service use; T2 was conducted six months later. Activities of daily living (ADL) and Memory and Behaviour Problems (MBPC) were investigated. Family caregivers noted significantly more deficits on the ADL scale, and significantly more problems on the MBPC scale. These differences increased when subjective burden of the family caregiver was high. The longitudinal results showed that these differences in ADL and MBPC ratings remained remarkably stable, although there was an increase in deficit ratings in both groups.


POSTLARVAL GROWTH IN JUVENILE RHITHROPANOPEUS HARRISH.
Eyestalk removal accelerated the molt cycles of megalopal and juvenile (first through fifth crab instars) Rhithropanopeus harrisii. Eyestalkless crabs also demonstrated a greater increase in size at each ecdysis. The growth rate of eyestalkless crabs was approximately twice the rate measured in control crabs. Epidermal cell density measurements showed that the cell density was the same in intermolt fifth instar control and eyestalkless crabs. The results demonstrate that growth in juvenile crabs is under the influence of eyestalk neurosecretory centers and that growth is a result of epidermal cell proliferation and not cell enlargement.


Group I metabotropic glutamate receptors control proliferation, survival and differentiation of cultured neural progenitor cells isolated from the subventricular zone of adult mice.
Neural progenitor cells (NPCs) are found in the subventricular zone (SVZ) of the adult brain, a specialized neurogenic niche that might provide a substrate for brain repair after injury. The incomplete knowledge of how NPCs in the niche respond to local signals limits the use of cultured NPCs in the development of cell transplantation strategies. We show that neurospheres obtained from the SVZ of the adult mouse expressed functional mGlu1 and mGlu5 metabotropic glutamate receptors. Pharmacological blockade of mGlu5 receptors promoted the apoptotic death of progenitors undergoing differentiation into neurons (PSA/NCAM+ cells for the most part), whereas blockade of mGlu1 receptors reduced the proliferation rate of NPCs, and promoted their differentiation towards the neuronal lineage. We conclude that endogenous activation of mGlu5 receptors might support specifically the survival of neuronal-restricted precursors, whereas endogenous activation of mGlu1 receptors might sustain the proliferation of earlier progenitors. Moreover, mGlu1 receptor antagonists increased the survival of NPCs, suggesting that endogenously activated mGlu1 receptors might play a role in the natural cell loss regulating the number or the type of progenitors.


Fluctuating charge-density waves in a cuprate superconductor.
Cuprate materials hosting high-temperature superconductivity (HTS) also exhibit various forms of charge and spin ordering whose significance is not fully understood. So far, static charge-density waves (CDWs) have been detected by diffraction probes only at particular doping levels or in an applied external field . However, dynamic CDWs may also be present more broadly and their detection, characterization and relationship with HTS remain open problems. Here we present a method based on ultrafast spectroscopy to detect the presence and measure the lifetimes of CDW fluctuations in cuprates. In an underdoped La(1.9)Sr(0.1)CuO4 film (T(c) = 26 K), we observe collective excitations of CDW that persist up to 100 K. This dynamic CDW fluctuates with a characteristic lifetime of 2 ps at T = 5 K that decreases to 0.5 ps at T = 100 K. In contrast, in an optimally doped La(1.84)Sr(0.16)CuO4 film (T(c) = 38.5 K), we detect no signatures of fluctuating CDWs at any temperature, favouring the competition scenario. This work forges a path for studying fluctuating order parameters in various superconductors and other materials.


Plasminogen activator inhibitor-1 4G/5G polymorphism is associated with coronary artery disease risk: a meta-analysis.
The aim of the current study was to evaluate the association of PAI-1 4G/5G polymorphism with coronary artery disease (CAD) risk using a meta-analysis. All eligible studies were identified through a search of PubMed, EMBASE, China National Knowledge Infrastructure (CNKI), Database of Chinese Scientific and Technical Periodicals, and China Biology Medical literature database (CBM) before June 2014. The association between the PAI-1 4G/5G polymorphism and CAD risk was estimated by odds ratio (OR) and 95% confidence interval (CI). A total of 72 studies including 23557 cases and 21526 controls were eventually collected. The PAI-1 4G/5G polymorphism was significant associated with CAD risk in overall population (OR=1.19, 95% CI 1.10-1.28, P < 0.00001). The combination of adjusted ORs for CAD was 1.20 (95% CI 1.03-1.40, P=0.02). This polymorphism was associated with CAD risk in Caucasians (OR=1.10, 95% CI 1.02-1.19, P=0.01) and Asians (OR=1.46, 95% CI 1.21-1.75, P < 0.0001). This polymorphism significantly increased MI risk (OR=1.15, 95% CI 1.06-1.25, P=0.001). In the subgroup analysis by age, this polymorphism was significantly associated with early-onset CAD risk (OR=1.21, 95% CI 1.02-1.43, P=0.03). In the gender subgroup analyses, a statistically significant association was found in male CAD patients (OR=1.10, 95% CI 1.01-1.20, P=0.04). Both T2DM patients and non-T2DM patients carrying 4G allele showed increased CAD risks (OR=2.23, 95% CI 1.27-3.92, P=0.005 and OR=1.64, 95% CI 1.19-2.25, P=0.002, respectively). This meta-analysis suggested that PAI-1 4G/5G polymorphism was a risk factor for CAD.


Optimization of lasing in an inverted-opal titania photonic crystal cavity as an organic solid-state dye-doped laser.
Lasing performance of a dye-doped laser by encapsulating orange fluorescent dye 4-(Dicyanomethylene)-2-methyl-6-(4-dimethylaminostyryl)-4H-pyran (DCM) with different concentrations in a highly ordered three-dimensional (3D) inverted-opal titania (TiO2) photonic crystal (PC) microcavity was studied. The lasing threshold and laser quality were improved by optimizing the concentration of the laser dye DCM. When the concentration of DCM is optimized to 10-4 mol/l, the photoluminescence (PL) efficiency of DCM is sufficient to achieve lasing emission and meanwhile no fluorescence quantum quenching occurs. Therefore, the emission spectrum was greatly narrowed and the threshold was significantly improved, which reached 0.8 mJ pulse-1 cm-2. Our findings are promising results toward the realization of fabricating a highly efficient low-threshold organic laser.


[Prevalence of malnutrition in Spanish elders: systematic review].
Over the past years, several studies have examined the prevalence of malnutrition. The purpose of the present systematic literature review is to provide an overview of the current knowledge about the nutritional situation of elderly. Based on a literature research, studies with information about the prevalence of malnutrition published between 1995 and 2011 were considered. A total of 43,235 participants from 47 eligible studies were found. According to the Mini Nutritional Assessment, malnutrition was observed in 16.6% (95% confidence interval [95% CI] 0-62); according to anthropometric and biochemical parameters, malnutrition was observed in 21.4% (95% CI 2-77.3) and, when other nutritional indexes were used, malnutrition was observed in 47.3% (95% CI 10.6-94.7). Prevalence rates of malnutrition were highest in studies with a high proportion of patient who were severely disabled, had hip fracture or swallowing problems. It can be concluded that malnutrition is generally widespread and is highly variable, according to parameters used for nutritional assessment, health related problems or the population under study. Future studies should use standardized nutritional assessment tools in order to improve the prognosis of malnutrition in the elderly and achieve better comparability of study results.


The effects of a walking program on body composition and serum lipids and lipoproteins in overweight women.
Few prospective studies have been conducted with women to examine the effects of walking on body composition and serum lipid profiles. Overweight women were randomly assigned to either an exercise EX (no. 18) or a nonexercise NEX (no. 18) group. The EX group participated in five 45 min sessions/week of brisk walking at 62 +/- 2% VO2max for 15 weeks. Statistical analysis (2 x 3 repeated measures ANOVA) revealed that the pattern of change in total body weight [F(2.68) = 6.65, p = 0.002] but not body fat percentage, was significantly different between EX and NEX groups; NEX subjects had a 1.6 +/- 0.5 kg gain in contrast to no change in EX subjects. The pattern of change in serum triglycerides, total cholesterol, and LDL-C was not significantly different between groups. The interaction statistic for HDL-C, however, was significant [Pillais Trace (2.33) = 3.73, p = 0.035] with HDL-C tending to rise in the NEX group in contrast to a small decrease in the EX group. Change in kilocalorie intake was positively correlated with change in HDL-C, total cholesterol, and body weight. Change in body weight also correlated positively with change in HDL-C. Our findings suggest that moderate exercise training alone may not be a sufficient stimulus to affect body composition and serum lipid profiles favorably in overweight women.


Fabrication and characterization of nanopore-interfaced nanochannel devices.
Nanofluidic devices combining nanochannels and nanopores may enable a range of novel applications in the field of single-molecule biosensing and manipulation. Here we combine classic lithographically based fabrication and electron beam milling to construct a device that integrates sealed transverse features, such as nanocavities and nanochannels, with embedded pores vertically intersecting the nanochannels. Using fluorescent microscopy, we demonstrate that DNA molecules can be introduced into the nanochannels and translated transversely across the embedded pore in an extended-conformation without undergoing cross-pore translocation. Upon application of a trans-pore voltage drop, the molecules will undergo cross-pore translocation into an adjoining macroscopic reservoir.


Regulated expression of globin chains and the erythroid transcription factor GATA-1 during erythropoiesis in the developing mouse.
Erythropoiesis in vertebrates is characterized by sequential changes in erythropoietic site, erythroblast morphology, and hemoglobin synthesis. We have examined the expression of globin chains and the major erythroid transcription factor GATA-1 (previously known as GF-1/NF-E1/Eryf 1) from days 7.5 to 17.5 of mouse development. mRNAs for embryonic (epsilon y2, beta H1, and zeta) and adult (alpha and beta) globin chains were quantitated by RNase protection assays. Switching of globins within the alpha-globin cluster (alpha and zeta) was not strictly coordinated with that within the beta-globin cluster (epsilon y2, beta H1, and beta). Regulation of globin switches during development was primarily transcriptional. Of particular note, we found two developmental switches (beta H1 to epsilon y2 and epsilon y2 to beta) in the mouse, more analogous than previously thought to shifts found in human development. The erythroid transcription factor GATA-1, believed to be a principal regulator of genes expressed in erythroid cells, first appeared in the embryo in yolk sac at the time of blood island formation and remained at a low level during embryonic erythropoiesis (8 to 11 days) relative to that found later in fetal liver (12 to 15 days). The rise in GATA-1 mRNA in fetal liver paralleled and preceded the rapid accumulation of adult beta-globin RNA. RNase protection assays and a GATA-1-specific peptide antiserum were used to establish that a single GATA-1 polypeptide is expressed throughout mouse development. Overall, these findings suggest that the levels of this erythroid transcription factor during development may contribute to the differential gene activation characteristic of definitive versus primitive erythropoiesis.


Prediction of Collision Cross-Section Values for Small Molecules: Application to Pesticide Residue Analysis.
The use of collision cross-section (CCS) values obtained by ion mobility high-resolution mass spectrometry has added a third dimension (alongside retention time and exact mass) to aid in the identification of compounds. However, its utility is limited by the number of experimental CCS values currently available. This work demonstrates the potential of artificial neural networks (ANNs) for the prediction of CCS values of pesticides. The predictor, based on eight software-chosen molecular descriptors, was optimized using CCS values of 205 small molecules and validated using a set of 131 pesticides. The relative error was within 6% for 95% of all CCS values for protonated molecules, resulting in a median relative error less than 2%. In order to demonstrate the potential of CCS prediction, the strategy was applied to spinach samples. It notably improved the confidence in the tentative identification of suspect and nontarget pesticides.


Sulfatase-activated fluorophores for rapid discrimination of mycobacterial species and strains.
Most current diagnostic tests for tuberculosis do not reveal the species or strain of pathogen causing pulmonary infection, which can lead to inappropriate treatment regimens and the spread of disease. Here, we report an assay for mycobacterial strain assignment based on genetically conserved mycobacterial sulfatases. We developed a sulfatase-activated probe, 7-hydroxy-9H-(1,3-dichloro-9,9-dimethylacridin-2-one)-sulfate, that detects enzyme activity in native protein gels, allowing the rapid detection of sulfatases in mycobacterial lysates. This assay revealed that mycobacterial strains have distinct sulfatase fingerprints that can be used to judge both the species and lineage. Our results demonstrate the potential of enzyme-activated probes for rapid pathogen discrimination for infectious diseases.


Regional-Scale Spatio-Temporal Analysis of Anastrepha ludens (Diptera: Tephritidae) Populations in the Citrus Region of Santa Engracia, Tamaulipas, Mexico.
Large citrus areas in Tamaulipas are affected by Anastrepha ludens (Loew) populations. Here we report the findings of a spatio-temporal analysis of A. ludens on an extended citrus area from 2008-2011 aimed at analyzing the probabilities of A. ludens infestation and developing an infestation risk classification for citrus production. A Geographic Information System combined with the indicator kriging geostatistics technique was used to assess A. ludens adult densities in the spring and fall. During the spring, our models predicted higher probabilities of infestation in the western region, close to the Sierra Madre Oriental, than in the east. Although a patchy distribution of probabilities was observed in the fall, there was a trend toward higher probabilities of infestation in the west than east. The final raster models summarized the probability maps using a three-tiered infestation risk classification (low-, medium-, and high risk). These models confirmed the greater infestation risk in the west in both seasons. These risk classification data support arguments for the use of the sterile insect technique and biological control in this extended citrus area and will have practical implications for the area-wide integrated pest management carried out by the National Program Against Fruit Flies in Tamaulipas, Mexico.


The economic cost of using restraint and the value added by restraint reduction or elimination.
The purpose of this study was to calculate the economic cost of using restraint on one adolescent inpatient service and to examine the effect of an initiative to reduce or eliminate the use of restraint after it was implemented. A detailed process-task analysis of mechanical, physical, and medication-based restraint was conducted in accordance with state and federal restraint requirements. Facility restraint data were collected, verified, and analyzed. A model was developed to determine the cost and duration of an average episode for each type of restraint. Staff time allocated to restraint activities and medication costs were computed. Calculation of the cost of restraint was restricted to staff and medication costs. Aggregate costs of restraint use and staff-related costs for one full year before the restraint reduction initiative (FY 2000) and one full year after the initiative (FY 2003) were calculated. Outcome, discharge, and recidivism data were analyzed. A comparison of the FY 2000 data with the FY 2003 data showed that the adolescent inpatient service's aggregate use of restraint decreased from 3,991 episodes to 373 episodes (91 percent), which was associated with a reduction in the cost of restraint from $1,446,740 to $117,036 (a 92 percent reduction). In addition, sick time, staff turnover and replacement costs, workers' compensation, injuries to adolescents and staff, and recidivism decreased. Adolescent Global Assessment of Functioning scores at discharge significantly improved. Implementation of a restraint reduction initiative was associated with a reduction in the use of restraint, staff time devoted to restraint, and staff-related costs. This shift appears to have contributed to better outcomes for adolescents, fewer injuries to adolescents and staff, and lower staff turnover. The initiative may have enhanced adolescent treatment and work conditions for staff.


Minimum effective release rate of antifoulants.1. Effects of zosteric acid at Ford Island, Hawaii (USA).
Minimum effective release rate (MERR) of zosteric acid (ZA) was studied at Ford Island. At laboratory condition, spore attachment in Enteromorpha intestinalis was inhibited significantly at 28.2 microg cm2 of ZA. More than 95% reduction in spore attachment was achieved in Ulva fasciata at 2,000 microM of ZA through membrane diffusion system. At 40 cm depth level larval settlement was high with maximum number of Hydroides elegans settlement. The overall larval settlement was increased with increasing days of exposure. The MERR of 10 microg cm(-2) d(-1) ZA inhibited 50% of the larval settlement. However, the inhibition rate was not proportionate to the antifouling ZA concentration. Using MERR membrane diffusion system an effective antifouling strategy was suggested for Ford Island.


A classical ride through a conical intersection.
Regarding the correlated electron-nuclear motion in a model system, we investigate the dynamics in the vicinity of a conical intersection (CoIn) between two excited state potential surfaces. It is documented that an ensemble of classical trajectories which move in the complete electronic-nuclear phase space tracks the quantum wave-packet motion through the CoIn which is accompanied by a non-adiabatic population transfer. On the contrary, for an adiabatic circular motion around the position of the CoIn, the quantum mechanical and classical densities deviate substantially. In the latter case, the Born-Oppenheimer classical nuclear motion on a single potential surface is able to track the quantum dynamics.


Catalytic reduction of carbon dioxide by a zinc hydride compound, [Tptm]ZnH, and conversion to the methanol level.
The zinc hydride compound, [Tptm]ZnH, may achieve the reduction of CO2 by (RO)3SiH (R = Me, Et) to the methanol oxidation level, (MeO)xSi(OR)4-x, via the formate species, HCO2Si(OR)3. However, because insertion of CO2 into the Zn-H bond is more facile than insertion of HCO2Si(OR)3, conversion of HCO2Si(OR)3 to the methanol level only occurs to a significant extent in the absence of CO2.


"Through-Space" Relativistic Effects on NMR Chemical Shifts of Pyridinium Halide Ionic Liquids.
We have investigated, using two-component relativistic density functional theory (DFT) at ZORA-SO-BP86 and ZORA-SO-PBE0 level, the occurrence of relativistic effects on the 1 H, 13 C, and 15 N NMR chemical shifts of 1-methylpyridinium halides [MP][X] and 1-butyl-3-methylpyridinium trihalides [BMP][X3 ] ionic liquids (ILs) (X=Cl, Br, I) as a result of a non-covalent interaction with the heavy anions. Our results indicate a sizeable deshielding effect in ion pairs when the anion is I- and I3- . A smaller, though nonzero, effect is observed also with bromine while chlorine based anions do not produce an appreciable relativistic shift. The chemical shift of the carbon atoms of the aromatic ring shows an inverse halogen dependence that has been rationalized based on the little C-2s orbital contribution to the σ-type interaction between the cation and anion. This is the first detailed account and systematic theoretical investigation of a relativistic heavy atom effect on the NMR chemical shifts of light atoms in the absence of covalent bonds. Our work paves the way and suggests the direction for an experimental investigation of such elusive signatures of ion pairing in ILs.


Ileocolic intussusception precipitated by diagnostic colonoscopy: a case report.
Only 5% of all cases of intussusceptions occur in adults. Intussusception complicating colonoscopy is an extremely rare event. Herein, we present a case of a 58-year-old man who developed ileocolic intussusception after a colonoscopy during which an adenomatous polyp was discovered in the terminal ileum. Eight hours after colonoscopy, the patient developed diffuse abdominal pain associated with vomiting and bloody diarrhea. A contrast-enhanced abdominal computed tomography scan revealed features of mechanical intestinal obstruction and a round soft tissue mass inside the right colon, followed by the wall of the intussusceptum. Emergency laparotomy revealed extended ileocecal intussusception with the polyp incarcerated by the ileocecal valve. A typical right hemicolectomy was performed, and the patient had an uneventful recovery. Histologic examination of the surgical specimen revealed an inflammatory fibroid polyp. Ileocolic intussusception due to an ileal polyp may be precipitated by colonoscopy and should be included in the differential diagnosis of acute abdomen after colonoscopy.


Methotrexate-induced mucositis in acute leukemia patients is not associated with the MTHFR 677T allele in Mexico.
Methylenetetrahydrofolate reductase (MTHFR) has two common variants with reduced activity due to polymorphisms at nucleotides 677 and 1298. Both affect folate metabolism and thus remethylation of homocysteine, but are also thought to affect nucleotide synthesis and DNA methylation. Methotrexate (MTX), which interrupts folate metabolism, is used in the treatment of a variety of diseases including acute lymphoblastic leukemia (ALL), but exerts in some patients toxic effects on fast dividing tissues such as mucosal epithelia. The enhanced toxicity may be due to cooperative effects between MTX and MTHFR variants. Accordingly, it has been reported that carrying the 677T allele of the MTHFR is a risk factor for MTX-associated mucositis. As in the Mexican population, which is characterized by a high prevalence of the 677T MTHFR variant, several of its commonly associated defects have not been observed, we investigated the relationship between MTX toxicity and the 677T allele. Out of 28 patients with ALL (CC: 2, CT: 10, TT: 16), 16 had episodes of MTX-associated mucositis (CC: 0, CT: 6, TT: 10). Neither at the gene level nor at the genotype level was a significant association with mucositis found. It may be postulated that the risk of higher MTX toxicity in patients with decreased MTHFR activity could be neutralized by the normally folate rich diet in Mexico.


[NODULAR POLYARTERITIS ASSOCIATED WITH HEPATITIS B VIRUS (A CASE STUDY)].
This study is focused on a case of nodular polyarteritis associated with hepatitis B virus successfully treated by immunosuppressive and antiviral agents.


[Two cases of negative pressure pulmonary edema after induction of anesthesia and extubation].
Two cases of negative pressure pulmonary edema are described. In one case, tracheal intubation was not successful and airway obstruction occurred after induction of anesthesia. Spontaneous breathing was restored by reversal of neuromuscular blocking action, but airway obstruction persisted. Urgent tracheostomy was therefore performed. A chest x-ray and clinical features indicated pulmonary edema immediately after tracheostomy. Treatment with mechanical ventilation and positive end-expiratory pressure improved pulmonary edema. In the other case, airway obstruction occurred after extubation. Removal of secretion in the oral cavity and assisted ventilation improved airway obstruction, but pulmonary edema was found by chest x-ray. Forced diuresis using furosemide and oxygen inhalation resulted in the improvement of pulmonary edema. Fortunatetly, in both cases, significant complications associated with pulmonary edema did not occur. Care should be taken of the risk of pulmonary edema when the airway was obstructed after induction of anesthesia or extubation under spontaneous breathing.


Coronavirus disease 2019 and acute cerebrovascular events: a comprehensive overview.
Since the Corona Virus Disease 2019 (COVID-19) pandemic, there has been increasing evidence that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with acute cerebrovascular events such as cerebral infarction, cerebral hemorrhage, and cerebral venous thrombosis. Although the mechanism of cerebrovascular complications among COVID-19 patients has not been adequately elucidated, the hypercoagulable state, excessive inflammation and ACE-2-associated alterations in the renin-angiotensin-aldosterone system after SARS-CoV-2 infection probably play an essential role. In this overview, we discuss the possible mechanisms underlying the SARS-CoV-2 infection leading to acute cerebrovascular events and review the characteristics of COVID-19-related acute cerebrovascular events cases and treatment options available worldwide.


Glucans as New Anticancer Agents.
For decades, glucans have been studied for their biological and immunological activities. The scientific community has mainly focused on immune reactions, but other areas, such as cholesterol levels and diabetic retinopathy, have shown the positive effects of glucan supplementation. However, the majority of studies focused on possible cancer suppression, where glucans showed clear and significant effects on numerous types of cancers, leading not only to clinical trials, but to approval as an official drug. The aim of this review is to describe the current knowledge of this field.


Late decompression in patients with acute facial nerve paralysis after temporal bone fracture.
The aim of this paper was to address the management of acute facial nerve paralysis after temporal bone fracture and the outcomes of late decompression. The study design was a retrospective review of eight patients who underwent late decompression of acute facial nerve paralysis due to temporal bone fracture involving the geniculate region. Pre-operative electrophysiological testing showed total degeneration of the facial nerve in all patients. The mean operation period was 70.1 +/- 54.8 days after the trauma. A pure middle fossa approach and combined approach included middle cranial fossa and transmastoid approaches and were used in six and two patients, respectively. Evaluation of the facial nerve function was graded according to the House-Brackmann grading scale. The mean follow up period was 5.7 +/- 3.2 years, ranging from 3 months to 10 years. Six patients showed 3 score of House-Brackmann recovery of facial nerve function in long-term follow-up and the last 2 patients still need time for their final House-Brackmann evaluation. Surgery should be performed if serial electroneurography and electromyography demonstrate more than 90% degeneration and total denervation potentials, respectively, of nerve fibers. Based on the outcomes observed, late facial nerve decompression may have still beneficial effects in patients who could not be operated on early.


Distinguishing drift and selection empirically: "the great snail debate" of the 1950s.
Biologists and philosophers have been extremely pessimistic about the possibility of demonstrating random drift in nature, particularly when it comes to distinguishing random drift from natural selection. However, examination of a historical case--Maxime Lamotte's study of natural populations of the land snail, Cepaea nemoralis in the 1950s--shows that while some pessimism is warranted, it has been overstated. Indeed, by describing a unique signature for drift and showing that this signature obtained in the populations under study, Lamotte was able to make a good case for a significant role for drift. It may be difficult to disentangle the causes of drift and selection acting in a population, but it is not (always) impossible.


Seven-coordinate iron and manganese complexes with acyclic and rigid pentadentate chelates and their superoxide dismutase activity.
The reactions of seven-coordinate [Fe(III)(dapsox)(H(2)O)(2)]ClO(4).H(2)O (1), [Fe(II)(H(2)dapsox)(H(2)O)(2)](NO(3))(2).H(2)O (2), and [Mn(II)(H(2)dapsox)(CH(3)OH)(H(2)O)](ClO4)2(H2O) (3) complexes of the acyclic and rigid pentadentate H(2)dapsox ligand [H2dapsox = 2,6-diacetylpyridinebis(semioxamazide)] with superoxide have been studied spectrophotometrically, electrochemically, and by a submillisecond mixing UV/vis stopped-flow in dimethyl sulfoxide (DMSO). The same studies were performed on the seven-coordinate [Mn(II)(Me(2)[15]pyridinaneN(5))(H(2)O)(2)]Cl(2).H(2)O (4) complex with the flexible macrocyclic Me(2)[15]pyridinaneN(5) ligand (Me(2)[15]pyridinaneN(5) = trans-2,13-dimethyl-3,6,9,12,18-pentaazabicyclo[12.3.1]octadeca-1(18),14,16-triene), which belongs to the class of proven superoxide dismutase (SOD) mimetics. The X-ray crystal structures of 2-4 were determined. All complexes possess pentagonal-bipyramidal geometry with the pentadentate ligand in the equatorial plane and solvent molecules in the axial positions. The stopped-flow experiments in DMSO (0.06% of water) reveal that all four metal complexes catalyze the fast disproportionation of superoxide under the applied experimental conditions, and the catalytic rate constants are found to be (3.7 +/- 0.5) x 10(6), (3.9 +/- 0.5) x 10(6), (1.2 +/- 0.3) x 10(7), and (5.3 +/- 0.8) x 10(6) M(-1) s(-1) for 1-4, respectively. The cytochrome c McCord-Fridovich (McCF) assay in an aqueous solution at pH = 7.8 resulted in the IC(50) values (and corresponding kMcCF constants) for 3 and 4, 0.013 +/- 0.001 microM (1.9 +/- 0.2 x 10(8) M(-1) s(-1)) and 0.024 +/- 0.001 microM (1.1 +/- 0.3 x 10(8) M(-1) s(-1)), respectively. IC(50) values from a nitroblue tetrazolium assay are found to be 6.45 +/- 0.02 and 1.36 +/- 0.03 microM for 1 and 4, respectively. The data have been compared with those obtained by direct stopped-flow measurements and discussed in terms of the side reactions that occur under the conditions of indirect assays.


Dai-kenchu-to enhances accelerated small intestinal movement.
The present study was conducted to clarify the effects of Dai-kenchu-to on accelerated small intestinal movement. We evaluated the effects of Dai-kenchu-to and its constituent herbs (dried ginger root, ginseng, zanthoxylum fruit, and malt sugar) on carbachol-accelerated mouse small intestinal transit, and contractions induced by low-frequency electrostimulation (ESC), KCl, or acetylcholine (ACh) using isolated guinea pig ileum. Dai-kenchu-to (10-300 mg/kg, p.o.) significantly improved carbachol-accelerated small intestinal transit in a dose-dependent manner. Using a concentration with the compounded rate for Dai-kenchu-to 300 mg/kg, carbachol-accelerated small intestinal transit was also significantly improved with a single dose of dried ginger root or ginseng. At a concentration of 3 x 10(-5) g/ml or less, Dai-kenchu-to, dried ginger root, and ginseng all inhibited ESC but not KCl- or ACh-induced contractions. However, at a higher concentration of Dai-kenchu-to (10(-4) g/ml) or zanthoxylum fruit (10(-5) g/ml or more) the ESC were enhanced. Both Dai-kenchu-to and dried ginger root at 10(-3) g/ml remarkably inhibited the KCl-induced contractions. These results indicate that Dai-kenchu-to improves accelerated small intestinal movement and that dried ginger root and ginseng may be involved in this effect. It is also thought that the mechanisms mainly involve the direct inhibition of smooth muscle but with a contribution from neural inhibition.


[Paresis of the brachial plexus: subcapital varus osteotomy, arthrodesis of shoulder joint and above-elbow amputation (author's transl)].
In brachial plexus paresis with partial sensory sparing in the upper arm and complete motor paralysis we amputate through the humerus at the distal limit of sensation. The remaining proximal humerus is fixed by an arthrodesis of the shoulder joint, combined with a varus-osteotomy below the head. This increases with axillary space, facilitates the fitting of a prosthesis and improves care of the skin in this critical area. It also improves the outline of the shoulder the muscles of which shrink.


Electrochemical oxidation of hydrolyzed poly oxymethylene-dimethyl ether by PtRu catalysts on Nb-doped SnO(2-δ) supports for direct oxidation fuel cells.
We synthesized Pt and PtRu catalysts supported on Nb-doped SnO(2-δ) (Pt/Sn0.99Nb0.01O(2-δ), PtRu/Sn0.99Nb0.01O(2-δ)) for direct oxidation fuel cells (DOFCs) using poly oxymethylene-dimethyl ether (POMMn, n = 2, 3) as a fuel. The onset potential for the oxidation of simulated fuels of POMMn (methanol-formaldehyde mixtures; n = 2, 3) for Pt/Sn0.99Nb0.01O(2-δ) and PtRu/Sn0.99Nb0.01O(2-δ) was less than 0.3 V vs RHE, which was much lower than those of two commercial catalysts (PtRu black and Pt2Ru3/carbon black). In particular, the onset potential of the oxidation reaction of simulated fuels of POMMn (n = 2, 3) for PtRu/Sn0.99Nb0.01O(2-δ) sintered at 800 °C in nitrogen atmosphere was less than 0.1 V vs RHE and is thus considered to be a promising anode catalyst for DOFCs. The mass activity (MA) of PtRu/Sn0.99Nb0.01O(2-δ) sintered at 800 °C was more than five times larger than those of the commercial catalysts in the measurement temperature range from 25 to 80 °C. Even though the MA for the methanol oxidation reaction was of the same order as those of the commercial catalysts, the MA for the formaldehyde oxidation reaction was more than five times larger than those of the commercial catalysts. Sn from the Sn0.99Nb0.01O(2-δ) support was found to have diffused into the Pt catalyst during the sintering process. The Sn on the top surface of the Pt catalyst accelerated the oxidation of carbon monoxide by a bifunctional mechanism, similar to that for Pt-Ru catalysts.


Engineering connectivity by multiscale micropatterning of individual populations of neurons.
Functional networks are the basis of information processing in the central nervous system. Essential for their formation are guided neuronal growth as well as controlled connectivity and information flow. The basis of neuronal development is generated by guiding cues and geometric constraints. To investigate the neuronal growth and connectivity of adjacent neuronal networks, two-dimensional protein patterns were created. A mixture of poly-L-lysine and laminin was transferred onto a silanized glass surface by microcontact printing. The structures were populated with dissociated primary cortical embryonic rat neurons. Triangular structures with diverse opening angles, height, and design were chosen as two-dimensional structures to allow network formation with constricted gateways. Neuronal development was observed by immunohistochemistry to pursue the influence of the chosen structures on the neuronal outgrowth. Neurons were stained for MAP2, while poly-L-lysine was FITC labeled. With this study we present an easy-to-use technique to engineer two-dimensional networks in vitro with defined gateways. The presented micropatterning method is used to generate daisy-chained neuronal networks with predefined connectivity. Signal propagation among geometrically constrained networks can easily be monitored by calcium-sensitive dyes, providing insights into network communication in vitro.


Discordant synthesis and secretion of human chorionic gonadotropin and subunits by cervical carcinoma cells.
Epidermoid carcinoma of the cervix cell lines DoT and CaSki were examined for the production of human chorionic gonadotropin (HCG) and its subunits (HCG-alpha and HCG-beta). Additionally, the effect of butyrate and other regulatory agents on synthesis and secretion was investigated. Media and cell lysates were analyzed by radioimmunoassay for HCG and HCG-beta and by radioreceptor assay for intact HCG. Although DoT and CaSki cells secreted more HCG-beta than HCG, the cell lysates contained only one-half as much HCG-beta as HCG. This raises the possibility that HCG-alpha synthesis may be limiting to the formation of intact HCG in DoT and CaSki cell lines. Our results also indicate discordance in HCG and HCG-beta production in response to butyrate. Whereas the production of HCG-beta was increased by 5 mM sodium butyrate, the synthesis and secretion of intact hCG were decreased. These results support the concept of independent regulation of alpha- and beta-subunit synthesis and secretion.


Building Capacity for Cyberbiosecurity Training.
Cyberbiosecurity lies at the intersection of cybersecurity and biosecurity and addresses the protection of valuable biological material and associated information. As an emerging concept, cyberbiosecurity requires the integration of training strategies targeted to both current and future professionals; as well as an increased awareness in the wider stakeholder community. As the discrete discipline of cyberbiosecurity continues to develop, initial training efforts are likely to include workshops and specialized training that bridge the disciplines of information technology (IT) and life sciences. Potential threats, risks, and vulnerabilities will be defined, cooperative relationships formed, and collaborative solutions developed. As the scope of the training framework for assessing potential threats is adapted to various audiences, in-service trainings will ensure awareness and understanding of threats relevant to specific industries. This framework may also be incorporated into existing curricula across IT and science fields. The scope of potential threats is vast, and eventual specialization will likely fall within the realm of IT professionals, who carry the capability for action. In this paper, we identify stakeholders in the development of cyberbiosecurity training; discuss current training methods, educational requirements, and credentialing for professionals in cybersecurity, biosecurity, and life sciences; suggest mechanisms for integration of cyberbiosecurity training into existing training approaches; and discuss potential for future development of specialized professionals.


Predictors of Pharmacy Students' Attitudes About the Therapeutic Use of Psilocybin.
Background Psilocybin has been studied for its potential therapeutic benefits, particularly for the treatment of psychiatric disorders such as anxiety, depression, and obsessive-compulsive disorder. While more research is needed as psilocybin-assisted therapy becomes more prevalent, future pharmacists will probably be involved at some level. At present, pharmacists receive minimal training on psilocybin, and little is known about their attitudes toward its use for medical purposes. Findings from recent clinical studies have attempted to establish the safety and medical efficacy of psilocybin, leading to an increased interest in therapeutic psilocybin use in the United States. This study aimed to assess if self-assessed knowledge of psilocybin, concerns about adverse effects, and opinions about legalization will make statistically significant contributions to pharmacy students' attitudes about psilocybin use in practice. Methods Pharmacy students' self-assessed knowledge, concern for potential adverse effects, and perceptions of psilocybin were investigated using a cross-sectional survey study design. Data were collected from March 13 to April 7, 2023, from a convenience sample of 161 pharmacy students enrolled in an accredited pharmacy school in the southern region of the United States using a 41-item anonymous quantitative survey developed by the researchers that contained validated scales. The survey was delivered electronically. Multiple regression modeling was conducted to determine if self-assessed knowledge, concerns for adverse effects, and opinions about legalization would predict pharmacy students' attitudes about therapy-assisted psilocybin use. This study was approved by the Institutional Review Board of the authors' university. Results The mean age of the 161 participants was 24 years (SD = 2.981; range 20-40 years). Twenty (12.4%) participants reported previous use of psilocybin for recreational purposes and two (1.2%) reported having used it therapeutically. Many (n =121; 75.2%) of the participants believed that psilocybin should be decriminalized for therapeutic use, but only 54 (33.5%) thought it should be decriminalized for recreational use. A multiple linear regression model predicting "attitudes about psilocybin" (dependent variable) produced significant results: (F(4, 122) = 40.575, p < 0.001), with an R2 = 0.571 (adjusted R2 = 0.557). Greater "self-assessed knowledge about psilocybin," less "concern about possible negative effects," greater "belief in the decriminalization of psilocybin for recreational use," and greater "belief in the decriminalization of psilocybin for therapeutic use" (all independent variables) were associated with more positive perceptions about medical psilocybin. The percentage of variance in the scores accounted for by the model was 57%. Conclusions Pharmacy students may lack information and training regarding psilocybin and report a desire to learn more about it. Their attitudes about medical psilocybin may be driven by this desire to learn in addition to concerns about adverse effects and legalization issues. Due to the dearth of published information regarding the knowledge and acceptance of psilocybin as a viable treatment option for patients, further research in psychedelic-assisted treatments may be warranted.


Pectoralis Major Tendon Tear: A Critical Analysis Review.
Pectoralis major (PM) tendon tears are predominantly seen in young men, and the majority of tears occur as tendon avulsions involving the sternal head. Weightlifting, specifically bench-pressing, and sporting activities with eccentric overloading of the PM tendon are the 2 most common activities that result in PM injury. Early surgical repair or reconstruction should be offered to younger, active patients with a complete PM tear; the majority of the patients undergoing surgical repair achieve good-to-excellent outcomes. Nonsurgical treatment of a complete PM tear is an option but will result in cosmetic deformity and a deficit in adduction strength of the arm. Outcomes after nonsurgical treatment of complete PM tears are less satisfactory than those obtained after surgical treatment. Currently, there is no consensus on the chronological definition of PM tears (acute versus chronic), the critical time limit for performing surgical repair, the ideal fixation device (cortical button, bone tunnel, or suture anchors), the indications for allograft use, and the ideal rehabilitation protocol after treatment of PM tears.


Analysis of "Use of Blood Glucose Meters Featuring Color Range Indicators Improves Glycemic Control and Patients With Diabetes in Comparison to Blood Glucose Meters Without Color (ACCENTS Study)".
Self-monitoring of blood glucose is a part of integral care of patients with diabetes mellitus. Understanding and appropriately responding to glucose levels is a fundamental part of self-management. Grady et al's work, published in the current issue of Journal of Diabetes Science and Technology, investigated whether switching people with diabetes from their usual meter to a meter featuring color range indicator (CRI) could improve glycemic control, by facilitating improved understanding of blood glucose targets. In this small but well-designed study, the authors have shown that meters with CRI features offer a potential advantage and may improve glucose control in patients with diabetes, both with T1D and T2D, across the therapy spectrum from oral agents to insulin therapy.


Electrophoretic behaviour of human urinary amylase.
A saccharogenic method is described for estimating amylase activity in human urine. Results accord with those reported elsewhere except that in this study the peak in the beta zone is a new finding. Comparison between normal and pathological urines suggests that the amylase activity of the beta peak is not of pancreatic origin.


Metamorphosis from bone marrow derived primitive stem cells to functional liver cells.
Both stem cell plasticity and cell fusion have been implicated as physiological responses to tissue injury. It remains the ultimate goal for the future to understand the regulatory control of each during regeneration. In our recent paper by Jang et al. we demonstrate the repair of damaged liver by bone marrow derived stem cells (SCs) in response to microenvironmental cues. Within 48 hrs after transplantation or co-culture, conversion of SCs into liver cells was observed. Fusion was ruled out as a major mechanism of this functional regeneration. Direct differentiation of SCs into liver epithelial cells may be clinically useful. However, if plasticity or fusion results in abnormal genetic changes they could be harmful. Before proceeding with therapeutic applications, the consequences of cellular therapy accompanying both plasticity and fusion must be examined in multiple animal models. Functional repair should also be demonstrated prior to treatment in patients.


Human red cell glycolysis in high altitude chronic hypoxia.
We have found that glycolysis in human red blood cells under the hypoxic conditions found at high altitudes is connected with changes in enzyme activities and levels of various metabolic intermediates. The sensitivity of the four kinases to hypoxia results in 1) glycolytic hyperactivity leading to a higher intracellular energy state, and 2) accumulation of 2-3 DPG, whose role in the adaptation of red blood cell respiration to high altitude has been shown by previous research. PEP, 3PG , and G6P appear to be the main regulating intermediates in glycolysis in this system. The reason for the very large increase in G1- 6DP is still not clear.