Impact of water quality on setting of irreversible hydrocolloid impression materials.
Setting of irreversible hydrocolloid impression materials is based on the ionic reaction between carboxylic groups and calcium ions and may, therefore, be affected by ionic species present in the mixing water. The impact of this phenomenon on the clinical performance of these materials has not been well documented. The purpose of this study was to compare the setting behavior of irreversible hydrocolloid impression materials when mixed with tap and distilled water, and to determine the impact of typical cations present in tap water and their concentrations on the setting process. Six brands of irreversible hydrocolloid impression materials (Kromopan 100, Xantalgin Select FS, Alginoplast, Elastic Plus, Ypeen, and Ypeen Premium) were mixed with tap and distilled water (control) according to manufacturers' recommendations. Elastic Plus was also mixed with aqueous solutions containing various concentrations of NaCl, CaCl(2), and AlCl(3) to determine the role of typical cations on setting. Using a controlled shear stress oscillatory rheometer, time changes of storage (G') and loss (G'') moduli during setting were measured at 23 degrees C and used to determine the working and setting times and rigidity of set impression materials. The sample size (n=3) for each material/mixing system was increased to 8 to increase reliability of measurements in systems where the effect of mixing water was low or variance of results was high. The data were analyzed (alpha=.05) using a t test (tap water), a 1-way ANOVA, a Tukey post hoc test (shear stress), and a nested ANOVA and Fisher Least Significant Difference post hoc analysis (cation and cation concentration). Statistical analysis showed significant (P<.001) acceleration in the setting rate for Kromopan 100, the working time of which was shorter with tap water by 23.4 seconds and the setting time, by 32.8 seconds. Similar significant reductions (in seconds) in both working and setting times, respectively, were found with Xantalgin Select FS (12.0, P<.001 and 23.6, P<.002), Alginoplast (24.3, P<.001 and 44.7, P<.005), and Elastic Plus (23.0, P<.001 and 22.0, P<.002), when compared with the same materials mixed with distilled water. At the same time, the rigidity of the set impression materials mixed with tap water increased by approximately 10%. With Ypeen Premium, the setting time decreased significantly by 20.0 seconds (P<.001) with tap water, while the working time and rigidity did not change. The setting behavior of Ypeen was not significantly affected by water quality. Acceleration of the setting reactions and increase in impression rigidity depended (P<.001) primarily on concentration and valency of cations present in mixing water. Setting of irreversible hydrocolloid impression materials can be significantly accelerated when tap water with high water hardness is used for mixing or when the mixing water contains higher concentrations of cations such as Na(+), Ca(2+), and Al(3+).


WD40-repeat protein WDR18 collaborates with TopBP1 to facilitate DNA damage checkpoint signaling.
The genomes of all living organisms are exposed to a wide spectrum of insults. To maintain genomic integrity, eukaryotes have evolved an elaborate surveillance mechanism - DNA damage checkpoint signaling - to detect damaged DNA and to arrest cell cycle progression, allowing time to process and repair DNA damage. TopBP1 plays multiple roles in the regulation of DNA damage checkpoint signaling. However, the molecular mechanism of how TopBP1 regulates ATR-mediated Chk1 phosphorylation is poorly understood. In this communication, we demonstrate (1) that the Chk1 activation domain of TopBP1 is critical in response to several different types of DNA damage; (2) that WD40-repeat protein WDR18 associates with the C-terminus of TopBP1 in vitro and in vivo; (3) that the association between WDR18 and TopBP1 is required for AT70-induced Chk1 phosphorylation; (4) and that WDR18 itself is required for AT70-triggered Chk1 phosphorylation. In addition, WDR18 associates with Chk1 in vitro. The data suggest that WDR18 facilitates ATR-dependent Chk1 phosphorylation via interacting with both C-terminus of TopBP1 and Chk1. Our findings indicate that WDR18 is a bona fide checkpoint protein and that WDR18 works together with TopBP1 to promote DNA damage checkpoint signaling.


Gabapentin reduces haloperidol-induced vacuous chewing movements in mice.
Tardive dyskinesia (TD) is a common adverse effect observed in patients with long-term use of typical antipsychotic medications. A vacuous chewing movement (VCM) model induced by haloperidol has been used to study these abnormalities in experimental animals. The cause of TD and its treatment remain unknown, but several lines of evidence suggest that dopamine receptor supersensitivity and gamma-aminobutyric acid (GABA) insufficiency play important roles in the development of TD. This study investigated the effects of treatment with the GABA-mimetic drug gabapentin on the development of haloperidol-induced VCMs. Male mice received vehicle, haloperidol (1.5 mg/kg), or gabapentin (GBP, 100 mg/kg) intraperitoneally during 28 consecutive days. Quantification of VCMs was performed before treatment (baseline) and on day 28, and an open-field test was also conducted on the 28th day of treatment. The administration of gabapentin prevented the manifestation of haloperidol-induced VCMs. Treatment with haloperidol alone reduced the locomotor activity in the open-field test that was prevented by co-treatment with gabapentin. We did not find any differences among the groups nor in the tyrosine hydroxylase (TH) or glutamic acid decarboxylase (GAD) immunoreactivity or monoamine levels in the striatum of mice. These results suggest that treatment with gabapentin, an analog of GABA, can attenuate the VCMs induced by acute haloperidol treatment in mice without alterations in monoamine levels, TH, or GAD67 immunoreactivity in the striatum.


[Clinical features of non-small cell lung cancer cases].
The aim of this study was to evaluate the clinical features of non-small cell lung cancer (NSCLC) cases that were diagnosed in our clinic. The patients who were diagnosed as NSCLC in our clinic between January 1988 and January 1999 were comprised the study group. The files and records of the study group were retrospectively reviewed to identify patients and all the data including demographic characteristics, history, physical examination findings, laboratory values, diagnostic procedures, radiologic findings and staging procedures. The study group included 564 patients (506 male, 58 female). The mean age was 60 years (28-97). 87% of the patients were current smokers or ex-smokers. The most frequent symptoms on admission were cough, sputum, and dyspnea. The most common radiologic finding was a central mass with a diameter of more than 4 cm with an irregular border. The diagnosis was established by histopathologic examination of biopsy specimens obtained by various means, in which bronchoscopy was the sole means of diagnosis in 83% of the patients. Histopathologic examination of the biopsy specimens resulted as follows: 85.8% squamous cell carcinoma, 10.3% adenocarcinoma, 1.4% large cell carcinoma, 0.45% adenosquamous carcinoma, and 2.1% undifferentiated NSCLC. Staging procedures that were done in all patients revealed that 85% of the patients were diagnosed at the stage IIIB and IV. Metastasis was most frequently to the bones followed by brain and liver. In our study squamous cell carcinoma was the most common histopathologic type with a higher percentage than the previous reports in the literature. The percentages of stage IIIB and IV were also higher in our study than previous papers in the literature.


Fluoxetine in social phobia: a double-blind, placebo-controlled pilot study.
The objective of the study was to examine the efficacy of fluoxetine in social phobia. Sixty subjects were randomly assigned to 14 weeks of double-blind therapy with either fluoxetine or placebo. Dose was fixed at 20 mg for fluoxetine during the first 8 weeks of double-blind treatment; during the final 6 weeks, the dose could be increased every two weeks by 20 mg to a maximum of 60 mg/day. An intentto-treat analysis was used. A significant change from baseline to endpoint was found for both fluoxetine and placebo on the Liebowitz Social Anxiety Scale. However, no significant difference was found between fluoxetine and placebo. The change for fluoxetine was somewhat lower than that found with other selective serotonin reuptake inhibitors, whereas the placebo response was greater. Fluoxetine failed to separate from placebo in this trial. It is unknown whether a larger dose for longer duration would have yielded separation from placebo. A higher than usual placebo response rate was found.


Induction of tyrosine phosphorylation in human MHC class II-positive antigen-presenting cells by stimulation with contact sensitizers.
To investigate the intracellular signaling mechanisms involved in the activation of APC by contact sensitizers, we studied the induction of tyrosine phosphorylation by these agents. Selective analysis of phosphotyrosine (p-tyr) in human Langerhans cells and different mononuclear cell types was achieved using a multicolor flow-cytometric technique. Stimulation with contact sensitizers revealed a distinct increase in p-tyr exclusively for MHC class II-positive cells. For different haptens, irritants, as well as activators of distinct signal transduction pathways, it was demonstrated that only strong sensitizers or the protein tyrosine phosphatase inhibitor sodium orthovanadate or cross-linking of MHC class II molecules were able to induce formation of p-tyr in human blood-derived dendritic cells serving as model for the dendritic cell family. This event required physiologic cell culture conditions and was blocked by specific inhibitors of protein tyrosine kinases. No evidence for the inhibition of protein tyrosine phosphatases by haptens was found. Western blot analysis of monocyte-enriched populations revealed an augmented phosphorylation of distinct proteins after hapten stimulation partly resembling the pattern noticed after cross-linking of HLA-DR molecules. In dendritic cells generated from mononuclear progenitors, the protein tyrosine kinase inhibitor genistein was able to block tyrosine phosphorylation as well as production of IL-1beta mRNA transcripts. Our data underline the unique capacity of haptens to activate APC and the important role of tyrosine phosphorylation for this process.


Perspectives of leprosy patients on MDT services after integration of NLEP functions into primary health care.
Sixty-five leprosy patients residing in rural Digapahandi block of Ganjam district were studied during July-August 2001 in order to ascertain their perspectives regarding different MDT services after NLEP functions were integrated into primary health care (PHC) in Orissa after September 1999. They included 43.08% multibacillary (MB) cases and 61.92% paucibacillary (PB) cases. Assessment was done by personal interviews of adult patients and the parents of child cases after verification of their treatment cards at the sub-centre. Patient's knowledge regarding the availability of MDT services under PHC services and utilization of these services were highlighted. Influence of different socio-demographic factors was also studied. Basing on the study results, recommendations were made for sustained NLEP functions through PHC in order to improve the utilization of MDT services, which will help in the elimination of leprosy.


[Gardnerella vaginalis as urinary pathogen].
To study the significance of Gardnerella vaginalis in urine by comparing urine culture results, leucocytes count and clinical findings. A total of 1,365 urine specimens submitted consecutively were inoculated on Bilayer media. G. vaginalis was recovered from 76 urine specimens with the following distribution: in 12 samples G. vaginalis was isolated as the only organism, 9 with counts > 10(5) CFU/ml and 3 between 10(5)-10(3); in the remaining 64 samples G. vaginalis was always found in counts > 10(5) CFU/ml but associated in 13 occasions with another organism and in 51 occasions with 2 or more organisms from the periurethral and vaginal flora. G. vaginalis in pure cultures corresponded to 8 women and 4 males whose ages ranged from 20 to 86 years. Six patients complained of symptoms of lower urinary tract infection (UTI), 3 had fever and in 3 the urine culture was practised as a control. Seven patients presented predisposing factors to UTI and 2 were pregnant. In only 2 cases pyuria was detected. Of 12 patients with pure cultures, only 3 were found to have G. vaginalis UTI. Our data indicate that G. vaginalis in urine not always implies an UTI and that this organism is found most often in patients with predisposing factors.


A 4-Phenoxyphenol Derivative Exerts Inhibitory Effects on Human Hepatocellular Carcinoma Cells through Regulating Autophagy and Apoptosis Accompanied by Downregulating α-Tubulin Expression.
Hepatocellular carcinoma (HCC) is a leading cancer worldwide. Advanced HCCs are usually resistant to anticancer drugs, causing unsatisfactory chemotherapy outcomes. In this study, we showed that a 4-phenoxyphenol derivative, 4-[4-(4-hydroxyphenoxy)phenoxy]phenol (4-HPPP), exerts an inhibitory activity against two HCC cell lines, Huh7 and Ha22T. We further investigated the anti-HCC activities of 4-HPPP, including anti-proliferation and induction of apoptosis. Our results showed that higher dosage of 4-HPPP downregulates the expression of α-tubulin and causes nuclear enlargement in both the Huh-7 and Ha22T cell lines. Interestingly, the colony formation results showed a discrepancy in the inhibitory effect of 4-HPPP on HCC and rat liver epithelial Clone 9 cells, suggesting the selective cytotoxicity of 4-HPPP toward HCC cells. Furthermore, the cell proliferation and apoptosis assay results illustrated the differences between the two HCC cell lines. The results of cellular proliferation assays, including trypan blue exclusion and colony formation, revealed that 4-HPPP inhibits the growth of Huh7 cells, but exerts less cytotoxicity in Ha22T cells. Furthermore, the annexin V assay performed for detecting the apoptosis showed similar results. Western blotting results showed 4-HPPP caused the increase of pro-apoptotic factors including cleaved caspase-3, Bid and Bax in HCC cells, especially in Huh-7. Furthermore, an increase of autophagy-associated protein microtubule-associated protein-1 light chain-3B (LC3B)-II and the decrease of Beclin-1 and p62/SQSTM1 were observed following 4-HPPP treatment. Additionally, the level of γH2A histone family, member X (γH₂AX), an endogenous DNA damage biomarker, was dramatically increased in Huh7 cells after 4-HPPP treatment, suggesting the involvement of DNA damage pathway in 4-HPPP-induced apoptosis. On the contrary, the western blotting results showed that treatment up-regulates pro-survival proteins, including the phosphorylation of protein kinase B (Akt) and the level of survivin on Ha22T cells, which may confer a resistance toward 4-HPPP. Notably, the blockade of extracellular signal-regulated kinases (ERK), but not Akt, enhanced the cytotoxicity of 4-HPPP against Ha22T cells, indicating the pro-survival role of ERK in 4-HPPP-induced anti-HCC effect. Our present work suggests that selective anti-HCC activity of 4-HPPP acts through induction of DNA damage. Accordingly, the combination of ERK inhibitor may significantly enhance the anti-cancer effect of 4-HPPP for those HCC cells which overexpress ERK in the future.


Three-bead steering microswimmers.
The self-propelled microswimmers have recently attracted considerable attention as model systems for biological cell migration as well as artificial micromachines. A simple and well-studied microswimmer model consists of three identical spherical beads joined by two springs in a linear fashion with active oscillatory forces being applied on the beads to generate self-propulsion. We have extended this linear microswimmer configuration to a triangular geometry where the three beads are connected by three identical springs in an equilateral triangular manner. The active forces acting on each spring can lead to autonomous steering motion; i.e., allowing the swimmer to move along arbitrary paths. We explore the microswimmer dynamics analytically and pinpoint its rich character depending on the nature of the active forces. The microswimmers can translate along a straight trajectory, rotate at a fixed location, as well as perform a simultaneous translation and rotation resulting in complex curved trajectories. The sinusoidal active forces on the three springs of the microswimmer contain naturally four operating parameters which are more than required for the steering motion. We identify the minimal operating parameters which are essential for the motion of the microswimmer along any given arbitrary trajectory. Therefore, along with providing insights into the mechanics of the complex motion of the natural and artificial microswimmers, the triangular three-bead microswimmer can be utilized as a model for targeted drug delivery systems and autonomous underwater vehicles where intricate trajectories are involved.


Interprofessional, older adult, team-based home visits: A 6-year prospective analysis.
This 6-year prospective study describes the impact on student attitudes of an innovative, interprofessional geriatrics curriculum (IPGC) focused on team-based care with older adults in a home-based community setting. Dental, medical, occupational therapy, pharmacy, physical therapy, and physician assistant students were placed into teams each led by faculty members from all of the professions. The curriculum consisted of five, four-hour sessions over one academic year. Teams met with a community-dwelling older adult three times. Students completed the Geriatric Assessment Scale (GAS) before and after the IPGC experience. At the conclusion, improvements in attitudes toward older adults in the GAS and its four domains - social value, medical care, compassion, and societal resources-were observed across a wide spectrum of students. Students with the lowest initial attitudes improved the most, as did the scores of the youngest students. Older students improved more than younger students in the social value domain (i.e., the perceived social value of older adults). Among disciplines, occupational therapy and social work students improved the most in the social value domain. This study demonstrates improvement in attitudes toward older adults from student involvement in IPGC that combines didactic and experiential learning through community partnerships in a home-based setting.


Dry Eye Signs and Symptoms Persist During Systemic Neutralization of IL-1β by Canakinumab or IL-17A by Secukinumab.
To evaluate whether inhibition of the proinflammatory cytokines IL-1β or IL-17A by canakinumab or secukinumab, respectively, influence the signs and symptoms of dry eye. In a randomized, double-masked, placebo-controlled, outpatient clinical trial, 72 patients with moderate to severe dry eye were randomly assigned in a 1:1:1 ratio to treatment with a single intravenous dose of canakinumab, of secukinumab, or of placebo. Signs and symptoms of dry eye were evaluated on the treatment day and 1 week, 4 weeks, and 8 weeks after treatment. The prespecified primary efficacy endpoint was corneal staining in the study eye 4 weeks after treatment. Secondary endpoints included tear production (Schirmer test), tear film breakup time, conjunctival redness, the ocular surface disease index (OSDI), the frequency of a desire for a topical ocular lubricant, and visual acuity. Of the 71 patients included in the analysis of safety, the rate of adverse events was similar between treatment groups. The course of corneal staining scores from baseline to 4 weeks, respectively, were for canakinumab 1.46 to 1.33 (P = 0.62 compared with placebo), for secukinumab 1.46 to 1.23 (P = 0.22), and for placebo 1.68 to 1.42. There were no changes in the other measures of efficacy beyond what was within the range expected for stochastic day-to-day variation. The results suggest that the inhibition of IL-1β or IL-17A obtained by systemic administration of neutralizing drugs does not influence the severity of dry eye.


Surgical Clipping of an Unruptured Large Inferiorly Projecting Anterior Communicating Artery Aneurysm With Chiasmopathy: 2-Dimensional Operative Video.
Anterior communicating artery (ACoA) aneurysms are a frequently encountered cerebrovascular entity that is associated with a high rupture rate at a smaller size and debilitating morbidity and mortality following rupture. The surgical management of ACoA aneurysms is highly dependent on the spatial orientation of the saccular projection, which is categorized as inferior, superior, anterior, or posterior. The inferiorly projecting aneurysms constitute a minority of all aneurysms involving the ACoA. The adherence of the aneurysm dome near the chiasm predisposes these patients to dome avulsion during frontal lobe retraction. This patient presented with a 1-mo history of progressive vision loss and was found to have a large inferiorly projecting ACoA saccular aneurysm measuring 2.04 cm × 1.54 cm with resultant chiasmopathy. The lesion was approached via a right modified orbitozygomatic craniotomy, which can provide a more favorable maximal angle of approach to the ACoA complex to avoid brain retraction. Intraoperative adenosine was administered to provide relaxation of the aneurysm dome to augment clip placement. Postoperatively, the patient's chiasmopathy demonstrated near-complete resolution. The patient gave informed consent for surgery and video recording. Institutional review board approval was deemed unnecessary. Used with permission from Barrow Neurological Institute, Phoenix, Arizona.


Nasolabial Perforator Flap for One-stage Reconstruction of Nasal Defects.
The excellent freedom of movement and range of this flap when based on a the nasolabial perforator flap have not been sufficiently explored. In this study, along with demonstrating the other key advantages of this flap over its traditional counterpart, we will endeavour to fill these lacunae in the available literature. From February 2009 to February 2012, twenty patients with nasal defects were repaired with a nasolabial perforator flap in the Department of Plastic and Cosmetic Surgery at Sir Ganga Ram Hospital, New Delhi. Of these, two patients (10%) underwent the procedure bilaterally. Thus, a total of 22 nasolabial perforator flap procedures were carried out. Prospectively, collected clinical records and data of each patient were retrospectively retrieved and reviewed to study the nasal defect and surgery done. All the twenty (100%) patients had good functional and aesthetic outcome. All patients who had nasal stenosis preoperatively had very good improvement in the patency of the nasal passages, breathing and nasal blockage with complete recovery of symptoms. The patients were entirely satisfied with the functional recovery. The reliability and versatility of the nasolabial perforator flap exceed its recognised application in reconstruction of nasal defects and it must form a part of every plastic surgeon's armamentarium.


Successful Liposteroid Therapy for a Recurrent Idiopathic Pulmonary Hemosiderosis with Down Syndrome.
Idiopathic pulmonary hemosiderosis (IPH) is a rare and life-threatening disorder. Early diagnosis and appropriate management are essential for their better prognosis and patients' quality of life (QOL). It is considered that Down syndrome patients with IPH have a worse prognosis compared to other IPH cases. A 2-year-old girl with Down syndrome received the diagnosis of IPH after two episodes of massive pulmonary hemorrhage requiring assist ventilation, who suffered from recurrent IPH during tapering period of oral corticosteroid, started liposteroid therapy. We report here a case of successful control of recurrent IPH and improved QOL enormously with tapering dose of corticosteroid after starting liposteroid therapy.


The total synthesis of (-)-cyanthiwigin F by means of double catalytic enantioselective alkylation.
Double catalytic enantioselective transformations are powerful synthetic methods that can facilitate the construction of stereochemically complex molecules in a single operation. In addition to generating two or more stereocentres in a single reaction, multiple asymmetric reactions also impart increased enantiomeric excess to the final product in comparison with the analogous single transformation. Furthermore, multiple asymmetric operations have the potential to independently construct several stereocentres at remote points within the same molecular scaffold, rather than relying on pre-existing chiral centres that are proximal to the reactive site. Despite the inherent benefits of multiple catalytic enantioselective reactions, their application to natural product total synthesis remains largely underutilized. Here we report the use of a double stereoablative enantioselective alkylation reaction in a concise synthesis of the marine diterpenoid (-)-cyanthiwigin F (ref. 8). By employing a technique for independent, selective formation of two stereocentres in a single stereoconvergent operation, we demonstrate that a complicated mixture of racemic and meso diastereomers may be smoothly converted to a synthetically useful intermediate with exceptional enantiomeric excess. The stereochemical information generated by means of this catalytic transformation facilitates the easy and rapid completion of the total synthesis of this marine natural product.


The pocketbook: Pharmacoeconomic issues related to intravenous immunoglobulin therapy.
Two analyses were conducted to compare the cost-effectiveness of different intravenous immunoglobulin (IGIV) formulations: IGIV purified by caprylate precipitation and chromatography (IGIV-C) and IGIV manufactured by an older solvent-detergent method (IGIV-S/D). The results indicated that IGIV-C is associated with cost savings for patients with primary immunodeficiency or idiopathic (immune) thrombocytopenic purpura (ITP). With primary immunodeficiency, the largest cost driver was hospitalizations, whereas with ITP, it was ancillary product use and, more specifically, additional IGIV therapy. Although differences were noted between the two IGIV formulations, the long-term cost consequences of administering these IGIV products are unclear. Further work is necessary to determine whether the results of these analyses can be generalized beyond these particular patients and to evaluate the effects on long-term health care costs.


Comparison of invasive and non-invasive treatment strategies in older patients with acute myocardial infarction complicated by cardiogenic shock (from the Polish Registry of Acute Coronary Syndromes - PL-ACS).
Cardiogenic shock (CS) continues to be the most important factor affecting the mortality rate of patients with acute myocardial infarctions (AMIs). However, controversy regarding the optimal treatment of older patients with AMIs complicated by CS still exists. The aim of this study was to compare the results of invasive (coronary angiography during index hospitalization) and noninvasive treatment strategies in patients aged ≥ 75 years with AMIs complicated by CS, defined as systolic blood pressure <90 mm Hg or need for hemodynamic support and end-organ hypoperfusion. A multicenter Polish registry that included data on patients with acute coronary syndromes was examined to identify patients with AMIs treated from October 2003 to May 2007. A total of 97,531 patients with AMIs were hospitalized, and 5.5% of those patients (n = 5,390) had CS on admission, including 1,976 patients aged ≥ 75 years (509 treated invasively and 1,467 treated noninvasively). In-hospital mortality was 55.4% in patients treated invasively and 69.9% in patients treated noninvasively (p <0.0001). After 6 months, the mortality rate was 65.8% in the invasive group and 80.5% in the noninvasive group (p <0.0001). Propensity score analysis, in which 499 patients of each group were analyzed after being matched for demographic and clinical data, confirmed the early and long-term benefits of the invasive strategy. In conclusion, applying the invasive strategy to patients with AMIs complicated by CS reduced in-hospital and 6-month mortality in patients aged ≥ 75 years.


Improving complementary feeding in Ghana: reaching the vulnerable through innovative business--the case of KOKO Plus.
Reaching vulnerable populations in low-resource settings with effective business solutions is critical, given the global nature of food and nutrition security. Over a third of deaths of children under 5 years of age are directly or indirectly caused by undernutrition. The Lancet series on malnutrition (2013) estimates that over 220,000 lives of children under 5 years of age can be saved through the implementation of an infant and young child feeding and care package. A unique project being undertaken in Ghana aims to bring in two elements of innovation in infant and young child feeding. The first involves a public-private partnership (PPP) to develop and test the efficacy and effectiveness of the delivery of a low-cost complementary food supplement in Ghana called KOKO Plus™. The second involves the testing of the concepts of social entrepreneurship and social business models in the distribution and delivery of the product. This paper shares information on the ongoing activities in the testing of concepts of PPPs, social business, social marketing, and demand creation using different delivery platforms to achieve optimal nutrition in Ghanaian infants and young children in the first 2 years of life. It also focuses on outlining the concept of using PPP and base-of-the-pyramid approaches toward achieving nutrition objectives.


Effects of dopaminergic treatment on functional cortico-cortical connectivity in Parkinson's disease.
Interactions between dorsal premotor cortex (PMd) and primary motor cortex (M1) and interhemispheric inhibition (IHI) between M1 are impaired in Parkinson's disease (PD). We used dual-site transcranial magnetic stimulation to compare effects of first-time levodopa application with chronic dopaminergic therapy on these interactions in PD. Twelve untreated PD patients were studied before and after their first-ever intake of levodopa. The effects of chronic dopaminergic medication were evaluated in 11 patients who had received regular dopaminergic medication for approximately 3 years. Nine of these patients were also measured after overnight withdrawal of medication. For IHI, conditioning stimuli (CS) were applied to left M1 followed by test stimuli (TS) over right M1 and vice versa in separate blocks at interstimulus intervals (ISI) of 6-10 ms. Next, CS were applied to left PMd at subthreshold intensity followed by TS over left M1 at ISIs of 4 and 6 ms. Results were compared to 17 age- and gender-matched controls. In de novo PD patients, levodopa reduced left-to-right IHI, but did not alter PMd-M1 connectivity. In contrast, inhibitory PMd-M1 connectivity was present in early disease patients under chronic dopaminergic stimulation, but not in de novo PD patients at low stimulus intensities at an ISI of 4 ms. First-time exposure to levodopa exerts different effects on cortico-cortical pathways than chronic dopaminergic stimulation in PD, suggesting a change in the responsiveness of cortico-cortical circuits during the course of PD.


Calculation of dose contributions of electron and charged heavy particles inside phantoms irradiated by monoenergetic neutron.
The radiation-transport code PHITS with an event generator mode has been applied to analyze energy depositions of electrons and charged heavy particles in two spherical phantoms and a voxel-based mouse phantom upon neutron irradiation. The calculations using the spherical phantoms quantitatively clarified the type and energy of charged particles which are released through interactions of neutrons with the phantom elements and contribute to the radiation dose. The relative contribution of electrons increased with an increase in the size of the phantom and with a decrease in the energy of the incident neutrons. Calculations with the voxel-based mouse phantom for 2.0-MeV neutron irradiation revealed that the doses to different locations inside the body are uniform, and that the energy is mainly deposited by recoil protons. The present study has demonstrated that analysis using PHITS can yield dose distributions that are accurate enough for RBE evaluation.


Protein intake regulation in adult obese (ob/ob) and lean mice: effects of nonprotein energy source and of supplemental tryptophan.
Adult obese (ob/ob) and lean mice were allowed to self-select between diets varying in level of protein and carbohydrate, or protein and fat. Obese and lean mice self-selected 29% and 26% of their energy, respectively, from protein when fed diets varying in protein and carbohydrate. Intake of protein decreased 45% in obese mice and 32% in lean mice when diets varying in level of protein and fat were fed. These reductions in protein intake were not associated with an elevation in brain serotonin (5-HT), a putative regulator of protein intake. When the tryptophan content of diets varying in protein and carbohydrate was quadrupled in an attempt to elevate brain 5-HT and thereby reduce protein intake in obese and lean mice, neither the level of brain 5-HT nor protein intake were affected. Under the conditions of these experiments we found no evidence that protein intake was inversely related to brain 5-HT levels in obese and lean mice, nor were we able to manipulate protein intake with dietary tryptophan supplementation. The reduced protein intake in obese and lean mice fed diets varying in level of protein and fat, rather than protein and carbohydrate, may result from their greater preference for a high-fat diet than for a high-carbohydrate diet.


An alternative approach to fishbone extraction.
We present a novel approach for a common ENT emergency. Under nasendoscopic guidance, a fishbone lodged in the pharynx can be removed with a suction catheter passed nasally.


PDSS1-Mediated Activation of CAMK2A-STAT3 Signaling Promotes Metastasis in Triple-Negative Breast Cancer.
Genomic alterations are crucial for the development and progression of human cancers. Copy-number gains found in genes encoding metabolic enzymes may induce triple-negative breast cancer (TNBC) adaptation. However, little is known about how metabolic enzymes regulate TNBC metastasis. Using our previously constructed multiomic profiling of a TNBC cohort, we identified decaprenyl diphosphate synthase subunit 1 (PDSS1) as an essential gene for TNBC metastasis. PDSS1 expression was significantly upregulated in TNBC tissues compared with adjacent normal tissues and was positively associated with poor survival among patients with TNBC. PDSS1 knockdown inhibited TNBC cell migration, invasion, and distant metastasis. Mechanistically, PDSS1, but not a catalytically inactive mutant, positively regulated the cellular level of coenzyme Q10 (CoQ10) and intracellular calcium levels, thereby inducing CAMK2A phosphorylation, which is essential for STAT3 phosphorylation in the cytoplasm. Phosphorylated STAT3 entered the nucleus, promoting oncogenic STAT3 signaling and TNBC metastasis. STAT3 phosphorylation inhibitors (e.g., Stattic) effectively blocked PDSS1-induced cell migration and invasion in vitro and tumor metastasis in vivo. Taken together, our study highlights the importance of targeting the previously uncharacterized PDSS1/CAMK2A/STAT3 oncogenic signaling axis, expanding the repertoire of precision medicine in TNBC. SIGNIFICANCE: A novel metabolic gene PDSS1 is highly expressed in triple-negative breast cancer tissues and contributes to metastasis, serving as a potential therapeutic target for combating metastatic disease.


Roles of PI3K pan-inhibitors and PI3K-δ inhibitors in allergic lung inflammation: a systematic review and meta-analysis.
Meta-analysis can be applied to study the effectiveness of the summary estimates for experimental papers, producing objective and unbiased results. We investigated the effects of phosphoinositide-3-kinase (PI3K) on the inflammatory profile in allergic mouse models, which are currently under development in signal transduction materials. PubMed, EMBASE and Web of Science databases were searched for relevant literature using the search terms " PI3K inhibitor" and "allergy" or "asthma". Cochrane Review Manager and R were used for handling continuous variables. The primary outcomes of the inflammatory profile were divided into cell counts and inflammatory cytokines. We used a random effects model to draw a forest plot. Through the database search and subsequent selection, 17 articles were identified. Regarding the cell counts, both the PI3K pan-inhibitors and PI3K-δ inhibitors effectively reduced the total cell counts, eosinophils, neutrophils and lymphocytes. In contrast to PI3K-δ inhibitors, PI3K pan-inhibitors effectively reduced macrophages. Regarding the inflammatory cytokines, PI3K pan-inhibitors and PI3K-δ inhibitors effectively reduced total IgE, IL-4, IL-5, IL-13, TNF-α, IL-1β, VEGF and had no effect on IL-6. Compared to the PI3K pan-inhibitors, which block all pathways, selective PI3K-δ inhibitors are expected to be relatively less toxic. Regarding the efficacy, PI3K-δ inhibitors have at least the same or better efficacy than PI3K pan-inhibitors in effector cells and inflammatory mediators.


Enhanced detection of Listeria spp. in farmstead cheese processing environments through dual primary enrichment, PCR, and molecular subtyping.
The incidence and ecology of Listeria spp. in farmstead cheese processing environments were assessed through environmental sampling conducted in nine different plants over a 10-week period. Environmental samples (n = 705) were examined for the presence of Listeria spp. by using three detection/isolation protocols. The use of dual enrichment methods, which allowed for the recovery of injured Listeria spp. (mUSDA), identified more Listeria species-positive samples with higher sensitivity than the standard USDA method. The addition of PCR to the mUSDA method identified the most Listeria monocytogenes-positive samples, achieving greater sensitivity of detection while substantially reducing time. Overall, 7.5% of samples were positive for Listeria spp., yielding 710 isolates, 253 of which were subtyped by automated ribotyping to examine strain diversity within and between plants over time. The isolation of specific ribotypes did not appear to be affected by the enrichment protocol used. Fifteen (2.1%) samples yielded L. monocytogenes isolates differentiated almost equally into ribotypes of lineages I and II. Of most concern was the persistent and widespread contamination of a plant with L. monocytogenes DUP-1042B, a ribotype previously associated with multiple outbreaks of listeriosis. Our results suggest that the extent of contamination by Listeria spp., notably L. monocytogenes, in farmstead cheese plants is comparatively low, especially for those with on-site farms. The results of this study also identified points of control for use in designing more effective Listeria spp. control and monitoring programs with a focus on ribotypes of epidemiological significance.


Criterialism versus Deliberativism.
The argument in this paper is that the position of Schneiderman, Jecker, and Jonsen (2017) suffers from the very flaws of which they accuse the Multiorganization Policy Statement, and that all the ethical and conceptual arguments speak in favor of the collaborative, deliberativist position that underlies the Multiorganization Statement. That position is that we should abandon self-sealing definitions of futility, which disguise the value judgments inherent in them, in favor of the evolving, collaborative process of decision-making.


Stimuli-responsive reagent system for enabling microfluidic immunoassays with biomarker purification and enrichment.
Immunoassays have been translated into microfluidic device formats, but significant challenges relating to upstream sample processing still limit their applications. Here, stimuli-responsive polymer-antibody conjugates are utilized in a microfluidic immunoassay to enable rapid biomarker purification and enrichment as well as sensitive detection. The conjugates were constructed by covalently grafting poly(N-isopropylacrylamide) (PNIPAAm), a thermally responsive polymer, to the lysine residues of anti-prostate specific antigen (PSA) Immunoglobulin G (IgG) using carbodiimide chemistry via the polymer end-carboxylate. The antibody-PNIPAAm (capture) conjugates and antibody-alkaline phosphatase (detection) conjugates formed sandwich immunocomplexes via PSA binding in 50% human plasma. The complexes were loaded into a recirculating poly(dimethylsiloxane) microreactor, equipped with micropumps and transverse flow features, for subsequent separation, enrichment, and quantification. The immunocomplexes were captured by heating the solution to 39 °C, mixed over the transverse features for 2 min, and washed with warm buffer. In one approach, the assay utilized immunocomplex solution that was contained in an 80 nL microreactor, which was loaded with solution at room temperature and subsequently heated to 39 °C. The assay took 25 min and resulted in 37 pM PSA limit of detection (LOD), which is comparable to a plate ELISA employing the same antibody pair. In another approach, the microreactor was preheated to 39 °C, and immunocomplex solution was flowed through the reactor, mixed, and washed. When the specimen volume was increased to 7.5 μL by repeating the capture process three times, the higher specimen volume led to immunocomplex enrichment within the microreactor. The resulting assay LOD was 0.5 pM, which is 2 orders of magnitude lower than the plate ELISA. Both approaches generate antigen specific signal over a clinically significant range. The sample processing capabilities and subsequent utility in a biomarker assay demonstrate the opportunity for stimuli-responsive polymer-protein conjugates in novel diagnostic technologies.


Immunotherapy for drug-refractory mucosal leishmaniasis.
Pentavalent antimony (Sb(v)) is the mainstay therapy for mucosal leishmaniasis (ML), but it is toxic, and relapses are common. Immunotherapy using a mixture of killed parasites, with or without bacille Calmette-Guerin, is an alternative but is used sporadically because of inconsistent results. We developed a defined immunotherapeutic antigen preparation for use in an observational, open-label trial to treat 6 patients with ML with a history of Sb(v) therapy failure. All patients were treated with the antigens thiol-specific antioxidant, Leishmania major stress inducible protein 1, Leishmania elongation initiation factor, and Leishmania heat shock protein 83, plus granulocyte-macrophage colony-stimulating factor. Patients underwent clinical and pathological evaluations before the initiation of immunotherapy and at 3, 6, 9, 12, 18, 24, and 60 months after. One month after the third injection, 1 patient showed complete clinical remission (CC) and remained disease free for the duration of the study. At the 9-month follow-up examination, 5 patients showed CC, and all patients were asymptomatic at a subsequent 5-year follow-up examination. These data support the concept that vaccine therapy with a defined antigen combination, used with standard chemotherapy, is a safe and effective approach to treat drug-refractory ML.


Traumatic rupture of the common duct in sclerosing cholangitis.
A women, 52 years, old, with Crohn's disease of the colon treated with colectomy 9 years earlier, got a blunt abdominal trauma in a car accident. At laparotomy two weeks after the accident an isolated transverse rupture of the common hepatic duct was found just below the confluence of the hepatic ducts. The rupture was successfully repaired by a direct anastomosis. Four years later the patient developed attacks of fever and jaundice. A cholangiogram now showed typical signs of sclerosing cholangitis and re-checking of cholangiograms taken after the primary repair revealed that the disease existed already at that time. The cholangitis is supposed to be a contributing factor to the rupture.


A Patient Infected with SARS-CoV-2 Presenting with Complete Heart Block.
Complete heart block is a rare presentation in a patient with COVID-19 infection that may result when the virus enters the myocardial cell by the angiotensin-converting enzyme-2 receptor. Here, we report a case of forty-nine-year male with COVID-19 with complete heart block (CHB).


Protein tyrosine phosphatase 1B participates in the down-regulation of erythropoietin receptor signalling.
Erythropoietin (EPO) is the principal hormone regulating the proliferation of erythroid precursors and their differentiation into erythrocytes. Binding of ligand to the cell-surface EPO-R (EPO receptor) induces dimerization and JAK2 (Janus kinase 2)-mediated tyrosine phosphorylation of the receptor. Less than 1% of the EPO-Rs are displayed on the cell surface; most of the receptor molecules are retained in intracellular compartments, including the ER (endoplasmic reticulum). Using pervanadate (PV) as a potent tool to inhibit cellular PTPs (protein tyrosine phosphatases), we demonstrated previously the accumulation of mature (endoglycosidase H-resistant) tyrosine-phosphorylated EPO-R [Cohen, Altaratz, Zick, Klingmuller and Neumann (1997) Biochem. J. 327, 391-397]. In the present study, we investigated the participation of the ER-associated PTP1B in the dephosphorylation of intracellular EPO-R. We demonstrate tyrosine phosphorylation of EPO-R in BOSC-23T cells co-expressing EPO-R and the 'substrate-trapping' mutant form of PTP1B, PTP1B D181A (referred to as PTP1BD). In vivo interaction between EPO-R and PTP1B suggested that PTP1B dephosphorylates the EPO-R intracellularly. Endoglycosidase H resistance of tyrosine-phosphorylated EPO-R in cells expressing PTP1BD suggested that mature EPO-R is dephosphorylated by PTP1B. Stimulation with EPO of cells co-expressing EPO-R and either PTP1BD or PTP1B resulted in an increase or decrease respectively in phosphotyrosine EPO-R. We thus suggest that PTP1B dephosphorylates EPO-stimulated EPO-R and participates in the down-regulation cascade of EPO-mediated signal transduction.


Clinical applications of exercise stress echocardiography in the treadmill with upright evaluation during and after exercise.
Exercise stress echocardiography is the most frequently used stress test in our laboratory. Exercise echocardiography is used mainly in the study of patients with coronary artery disease. However, the technique is increasingly being used to study other diseases. In our centre, we use an original methodology, published by us in 2000, in which we evaluate heart function during exercise in the treadmill. After the exercise, patients are maintained in orthostatic position when appropriate or lying down in left lateral decubitus for further evaluation. Since this method seems to increase the quality and the quantity of information obtained in so many clinical arenas, we now present a detailed review of this methodology and its applications.


Parasitic nematode interactions with mammals and plants.
Parasitic nematodes that infect humans, animals, and plants cause serious diseases that are deleterious to human health and agricultural productivity. Chemical and biological control methods have reduced the impact of these parasites. However, surviving environmental stages lead to persistent reinfection of host species. In addition, development of resistance to nematicides and anthelmintics by these parasites and reduced availability of some nematicides, for environmental protection, pose significant obstacles for current and future prospects of effective parasite control. Due to marked differences in host species, research on animal and plant parasitic nematodes often proceeds independently. Despite the differences between animals and plants, basic cellular properties are shared among these host organisms. Some common properties may be important for mechanisms [homologous or convergent (homoplastic)] by which nematodes successfully infect these diverse hosts or by which animal and plant hosts resist infections by these pathogens. Here we compare host/parasite interactions between plant parasitic nematodes (PPN) and animal parasitic nematodes, with an emphasis on mammalian hosts (MPN). Similarities and differences are considered in the context of progress on molecular dissection of these interactions. A comprehensive coverage is not possible in the space allotted. Instead, an illustrative approach is used to establish examples that, it is hoped, exemplify the value of the comparative approach.


TEM-induced structural evolution in amorphous Fe oxide nanoparticles.
Exposure to the high energy electron beam of a TEM changes the morphology of amorphous Fe oxide nanoparticles from solid spheres to hollow shells. Amorphous Fe oxide nanoparticles prepared via high-temperature methods using hexadecylamine and trioctylphosphine oxide surfactants were compared to crystalline gamma-Fe2O3 particles of similar size. Both sets of particles are fully characterized via SQUID magnetometry, X-ray powder diffraction, BET surface analysis, EPR spectroscopy, high-resolution transmission electron microscopy (TEM), and electron energy loss spectroscopy (EELS). Time-resolved TEM images reveal that the amorphous Fe oxide particles evolve from solid spheres into hollow shells in <2 min, whereas crystalline gamma-Fe2O3 are unaffected by the electron beam. The resulting nanocrystalline Fe oxide shells bear striking resemblance to core-shell nanocrystals, but are a result of a morphology change attributed to restructuring of particle voids and defects induced by quasi-melting in the TEM. These results thus imply that caution is necessary when using TEM to analyze nanoparticle core-shell and heterostructured nanoparticles.


Single molecular imaging and spectroscopy of conjugated polyelectrolytes decorated on stretched aligned DNA.
DNA is the prototype template for building nanoelectronic devices by self-assembly. The electronic functions are made possible by coordinating electronic polymer chains to DNA. This paper demonstrates two methods for fabrication of aligned and ordered DNA nanowires complexed with conjugated polyelectrolytes (CPEs). The complex can be formed either in solution prior to stretching or after stretching of the bare DNA on a surface. Molecular combing was used to stretch the complexes on surface energy patterned surfaces, and PMMA for the bare DNA. Single molecular spectroscopy, in fluorescence, and microscopy, in atomic force microscopy, give evidence for coordination of the short CPE chains to the aligned DNA.


[Assessment of selected vitamins content in daily food rations of obese patients].
The study objective was to evaluate the content of chosen vitamins soluble in fats (A, E) and in water (B1, B2 B6, B12, C, niacin, folic acid) in daily food rations of obese subjects, who are not on a reducing diet (201 obese women - BMI = 32.9 +/- 6.2 kg/ m2 and 60 men - BMI = 33.4 +/- 5.3 kg/m2). The mean age was 45.8 +/- 12.2 years for women and 48 +/- 13.5 years for men. Dietary habits were assessed using the 24 h dietary recall method. Computer program DIETA2 was used to evaluate the vitamin content in daily food rations. Vitamin intake was compared with safe levels for subjects with low physical activity. Low intake were observed in the consumption of vitamin B1 in women and B2 in men. Daily food rations of patients with excessive body mass (both women and men) met safe level daily requirements for vitamin E, niacin, folic acid, riboflavin (women), vitamin B6 (men). High intakes of vitamin A, B12, and C were noted both among obese women and men.


Hepatitis B virus and its sexually transmitted infection - an update.
incidence and prevalence: About 5% of the world's population has chronic hepatitis B virus (HBV) infection, and nearly 25% of carriers develop chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). The prevalence of chronic HBV infection in human immunodeficiency virus (HIV)-infected individuals is 5%-15%; HIV/HBV coinfected individuals have a higher level of HBV replication, with higher rates of chronicity, reactivation, occult infection, and HCC than individuals with HBV only. The prevalence of HBV genotype A is significantly higher among men who have sex with men (MSM), compared with the rest of the population. Molecular mechanisms of infection, pathology, and symptomatology: HBV replication begins with entry into the hepatocyte. Sodium taurocholate cotransporting polypeptide was identified in 2012 as the entry receptor of HBV. Although chronic hepatitis B develops slowly, HIV/HBV coinfected individuals show more rapid progression to cirrhosis and HCC. Transmission and protection: The most common sources of HBV infection are body fluids. Hepatitis B (HB) vaccination is recommended for all children and adolescents, and all unvaccinated adults at risk for HBV infection (sexually active individuals such as MSM, individuals with occupational risk, and immunosuppressed individuals). Although HB vaccination can prevent clinical infections (hepatitis), it cannot prevent 100% of subclinical infections. Treatment and curability: The goal of treatment is reducing the risk of complications (cirrhosis and HCC). Pegylated interferon alfa and nucleos(t)ide analogues (NAs) are the current treatments for chronic HBV infection. NAs have improved the outcomes of patients with cirrhosis and HCC, and decreased the incidence of acute liver failure.


Ventilator Weaning and Spontaneous Breathing Trials; an Educational Review.
The term "weaning" is used to describe the gradual process of decreasing ventilator support. It is estimated that 40% of the duration of mechanical ventilation is dedicated to the process of weaning. Spontaneous breathing trial (SBT) assesses the patient's ability to breathe while receiving minimal or no ventilator support. The collective task force in 2001 stated that the process of SBT and weaning should start by assessing whether the underlying cause of respiratory failure has been resolved or not. Weaning predictors are parameters that are intended to help clinicians predict whether weaning attempts will be successful or not. Although the international consensus conference in 2005 did not recommend their routine use for clinical decision making, researchers did not stop working in this area. In the present article, we review some of the recent studies about weaning predictors, criteria, procedure, as well as assessment for extubation a mechanically ventilated patient.


Myofibroblast depletion reduces kidney cyst growth and fibrosis in autosomal dominant polycystic kidney disease.
Autosomal dominant polycystic kidney disease (ADPKD) involves the development and persistent growth of fluid filled kidney cysts. In a recent study, we showed that ADPKD kidney cyst epithelial cells can stimulate the proliferation and differentiation of peri-cystic myofibroblasts. Although dense myofibroblast populations are often found surrounding kidney cysts, their role in cyst enlargement or fibrosis in ADPKD is unclear. To clarify this, we examined the effect of myofibroblast depletion in the Pkd1RC/RC (RC/RC) mouse model of ADPKD. RC/RC;αSMAtk mice that use the ganciclovir-thymidine kinase system to selectively deplete α-smooth muscle actin expressing myofibroblasts were generated. Ganciclovir treatment for four weeks depleted myofibroblasts, reduced kidney fibrosis and preserved kidney function in these mice. Importantly, myofibroblast depletion significantly reduced cyst growth and cyst epithelial cell proliferation in RC/RC;αSMAtk mouse kidneys. Similar ganciclovir treatment did not alter cyst growth or fibrosis in wild-type or RC/RC littermates. In vitro, co-culture with myofibroblasts from the kidneys of patients with ADPKD increased 3D microcyst growth of human ADPKD cyst epithelial cells. Treatment with conditioned culture media from ADPKD kidney myofibroblasts increased microcyst growth and cell proliferation of ADPKD cyst epithelial cells. Further examination of ADPKD myofibroblast conditioned media showed high levels of protease inhibitors including PAI1, TIMP1 and 2, NGAL and TFPI-2, and treatment with recombinant PAI1 and TIMP1 increased ADPKD cyst epithelial cell proliferation in vitro. Thus, our findings show that myofibroblasts directly promote cyst epithelial cell proliferation, cyst growth and fibrosis in ADPKD kidneys, and their targeting could be a novel therapeutic strategy to treat PKD.


Advanced Paternal Age Affects Sperm Count and Anogenital Distance in Mouse Offspring.
In Western society, couples increasingly delay parenthood until later in life. Overall, studies have focused on the reproductive performance of older parents or the impact of advanced maternal age on pregnancy outcomes, but few studies have examined how advanced paternal age (APA) affects offspring health. The aim of this study was to investigate the impact of increasing paternal age on offspring reproductive performance and long-term metabolic health in a mouse model. Here, the same adult B6D2F1/J male mice were mated at 4, 12, and 18 months of age with 6- to 10-week-old naturally cycling CF1 females to generate 3 offspring cohorts conceived at increasing paternal ages PA4, PA12, and PA18. The offspring resulting from mating the same fathers at different ages (n = 20 per age; 10 males and 10 females) were maintained up to 20 weeks of age and morphometric parameters, growth curve, and glucose tolerance were measured. We found that increasing paternal age was associated with a trend toward longer time to conception. Litter sizes were not significantly different. Reassuringly, metabolic parameters and growth curve were not different in the 3 cohorts of offspring. Most importantly, increased paternal age (PA4 vs PA18) was associated with a statistically significant decrease in sperm concentration, sperm motility, and anogenital distance in offspring. These changes raise concerns about the potential impact of APA on the reproductive fitness in males of the next generation.


[Pulmonary Hypertension in Takayasu Arteritis].
Takayasu arteritis is well-known rare form of large vessel vasculitis. Pulmonary involvement is observed in 50% of cases. However, pulmonary hypertension is a rare complication of pulmonary artery stenosis. In this article we present a rare clinical case of Takayasus arteritis with typical stenosis of subclavian, carotid arteries, and involvement of pulmonary arteries with development of severe pulmonary hypertension. The article also contains discussion of current methods of diagnosis and treatment of pulmonary artery stenosis in Takayasus arteritis with special focus on effectiveness and complications of angioplasty and surgery.


The importance of high-level training for nutrition scientists in Sub-Saharan Africa.
Can the African people investigate and critically analyse nutrition needs in their context, identify national or community nutrition problems, plan and evaluate nutrition programs, educate, and communicate scientific knowledge in nutrition without high-level trained staffs with a strong scientific base in human nutrition? Will they be able to tackle their nutrition problems without a sustainable organisation for long-term training and research? In this paper, an attempt is made to analyse factors that will contribute to improving human nutrition in Sub-Saharan Africa. The paper also highlights an experience of institutional capacity building in Senegal, West Africa.


Whispering-gallery modes promote enhanced optical backflow in a perforated dielectric microsphere.
Optical energy flow inside a dielectric microsphere is usually co-directed with the optical wave vector. At the same time, if the optical field in a microsphere is in resonance with one of the high-quality spatial eigenmodes (whispering-gallery modes- WGMs), a region of reverse energy flow emerges in the shadow hemisphere. This area is of considerable practical interest due to increased optical trapping potential. In this Letter, we consider a perforated microsphere with an air-filled pinhole fabricated along the particle diameter and numerically analyze the peculiarities of WGM excitation in a nanostructured microsphere. A pinhole isolates the energy backflow region of a resonant mode and changes a perforated microsphere into an efficient optical tweezer. For the first time, to the best of our knowledge, a multiple enhancement of the energy backflow intensity in the pinhole at a WGM resonance is revealed and we discuss the ways for its manipulation.


Infant mortality in Michigan's child welfare system.
This article reports findings from a study on infant mortality in Michigan's child welfare system. The findings indicate that postneonatal death rates for infants in foster care placement from 1980 to 1989 are substantially higher than those in the general population. Although infants in the child welfare system are likely to be at greater risk, this article suggests that some of these deaths were preventable. Recommendations are made to address this problem as well as other policy issues raised by the data.


Student-Led Objective Tutorial (SLOT) in Medical Education.
Purpose - To assess an innovative tutoring program named 'Student-Led Objective Tutorial' (SLOT) among undergraduate medical students. Method - The program was conceptualized by the Pharmacology Unit of Faculty of Medicine and Health Sciences, Asian Institute of Medicine Science & Technology (AIMST), Malaysia and implemented in the middle of 2005. A cohort of 246 medical undergraduate students (spread across 5 consecutive batches) participated. Following a brief explanation on the purpose and nature of SLOT, each batch was divided into small groups and was given a reading assignment on 4 previously delivered lecture topics. Each group was asked to prepare 3-5 multiple choice questions (MCQs) of their own in PowerPoint format to be presented, in turns, to the whole class on the day of SLOT. The proceedings were facilitated by 2 lecturers. Student feedback on the efficacy and benefits were assessed through an anonymous self administered questionnaire. Results - About 76% (188) of the students favored SLOT. The acceptance rate of SLOT was higher among males. There was no significant difference between batches in their opinions on whether to pursue SLOT in future. The most prevalent positive comment was that SLOT enhanced learning skills, and the negative comment being, it consumed more time. Conclusions - SLOT is a novel tutorial method which can offset faculty shortage with advantages like enhanced interest among teachers and learners, uniform reach of content, opportunities for group learning, and involvement of visual aids as teaching-learning (T-L) method. SLOT unraveled the students' potential of peer tutoring both inside as well as outside the classroom. Consumer tutors (students) can be tapped as a resource for SLOT for all subjects and courses in healthcare teaching.


Carbon Monoxide-Induced Stability and Atomic Segregation Phenomena in Shape-Selected Octahedral PtNi Nanoparticles.
The chemical and morphological stability of size- and shape-selected octahedral PtNi nanoparticles (NP) were investigated after different annealing treatments up to a maximum temperature of 700 °C in a vacuum and under 1 bar of CO. Atomic force microscopy was used to examine the mobility of the NPs and their stability against coarsening, and X-ray photoelectron spectroscopy to study the surface composition, chemical state of Pt and Ni in the NPs, and thermally and CO-induced atomic segregation trends. Exposing the samples to 1 bar of CO at room temperature before annealing in a vacuum was found to be effective at enhancing the stability of the NPs against coarsening. In contrast, significant coarsening was observed when the sample was annealed in 1 bar of CO, most likely as a result of Ni(CO)4 formation and their enhanced mobility on the support surface. Sample exposure to CO at room temperature prior to annealing led to the segregation of Pt to the NP surface. Nevertheless, oxidic PtOx and NiOx species still remained at the NP surface, and, irrespective of the initial sample pretreatment, Ni surface segregation was observed upon annealing in a vacuum at moderate temperature (T < 300 °C). Interestingly, a distinct atomic segregation trend was detected between 300 and 500 °C for the sample pre-exposed to CO; namely, Ni surface segregation was partially hindered. This might be attributed to the higher bonding energy of CO to Pt as compared to Ni. Annealing in the presence of 1 bar CO also resulted in the initial surface segregation of Ni (T < 400 °C) as long as PtOx and NiOx species were available on the surface as a result of the higher affinity of Ni for oxygen. Above 500 °C, and regardless of the sample pretreatment, the diffusion of Pt atoms to the NP surface and the formation of a Ni-Pt alloy are observed.


Comparing the optical properties and thermal stability of green (TbPO4), yellow (DyPO4), and red (PrPO4) emitting single crystal samples.
Blue, green and red-emitting phosphors for near-UV/blue based phosphor blend converted white-light emitting devices have been investigated extensively over the past years. Herein, we present our results on the optical spectroscopy of single crystal samples of TbPO4, DyPO4 and PrPO4 exhibiting prominent emission at green (545 nm), yellow (574 nm) and red (616 nm) region of the electromagnetic spectrum, respectively. We study the temperature dependence of their emission spectra for excitations at 365 and 455 nm, to mimic experimental conditions for phosphor converted light emitting diodes, to show that their thermal quenching temperature is 730 K for TbPO4 (excitation 365 nm), 490 and 520 K for DyPO4 (excitation at 365 and 455 nm), and 540 K for PrPO4 (excitation 455 nm). The TbPO4 emission does not show any considerable blue/red shift at elevated temperatures, while DyPO4 emission is observed close to the center of CIE coordinate diagram. The PrPO4 sample possesses high color purity which shows slight yellow-shift at elevated temperatures. The ground state of Pr3+ and Tb3+ are found to be within the band gap suggesting that both are able to trap holes from the valence band as evinced from the thermoluminescence glow curve data which shows peak maxima at 422 and 437 K due to hole release from the Pr4+ and Tb4+, respectively. The result suggests that the samples have large potential for solid state lighting devices upon choice of an appropriate excitation wavelength.


Sequential administration of nivolumab and ipilimumab with a planned switch in patients with advanced melanoma (CheckMate 064): an open-label, randomised, phase 2 trial.
Concurrent administration of the immune checkpoint inhibitors nivolumab and ipilimumab has shown greater efficacy than either agent alone in patients with advanced melanoma, albeit with more high-grade adverse events. We assessed whether sequential administration of nivolumab followed by ipilimumab, or the reverse sequence, could improve safety without compromising efficacy. We did this randomised, open-label, phase 2 study at nine academic medical centres in the USA. Eligible patients (aged ≥18 years) with unresectable stage III or IV melanoma (treatment-naive or who had progressed after no more than one previous systemic therapy, with an Eastern Cooperative Oncology Group performance status of 0 or 1) were randomly assigned (1:1) to induction with intravenous nivolumab 3 mg/kg every 2 weeks for six doses followed by a planned switch to intravenous ipilimumab 3 mg/kg every 3 weeks for four doses, or the reverse sequence. Randomisation was done by an independent interactive voice response system with a permuted block schedule (block size four) without stratification factors. After induction, both groups received intravenous nivolumab 3 mg/kg every 2 weeks until progression or unacceptable toxicity. The primary endpoint was treatment-related grade 3-5 adverse events until the end of the induction period (week 25), analysed in the as-treated population. Secondary endpoints were the proportion of patients who achieved a response at week 25 and disease progression at weeks 13 and 25. Overall survival was a prespecified exploratory endpoint. This study is registered with ClinicalTrials.gov, number NCT01783938, and is ongoing but no longer enrolling patients. Between April 30, 2013, and July 21, 2014, 140 patients were enrolled and randomly assigned to nivolumab followed by ipilimumab (n=70) or to the reverse sequence of ipilimumab followed by nivolumab (n=70), of whom 68 and 70 patients, respectively, received at least one dose of study drug and were included in the analyses. The frequencies of treatment-related grade 3-5 adverse events up to week 25 were similar in the nivolumab followed by ipilimumab group (34 [50%; 95% CI 37·6-62·4] of 68 patients) and in the ipilimumab followed by nivolumab group (30 [43%; 31·1-55·3] of 70 patients). The most common treatment-related grade 3-4 adverse events during the whole study period were colitis (ten [15%]) in the nivolumab followed by ipilimumab group vs 14 [20%] in the reverse sequence group), increased lipase (ten [15%] vs 12 [17%]), and diarrhoea (eight [12%] vs five [7%]). No treatment-related deaths occurred. The proportion of patients with a response at week 25 was higher with nivolumab followed by ipilimumab than with the reverse sequence (28 [41%; 95% CI 29·4-53·8] vs 14 [20%; 11·4-31·3]). Progression was reported in 26 (38%; 95% CI 26·7-50·8) patients in the nivolumab followed by ipilimumab group and 43 (61%; 49·0-72·8) patients in the reverse sequence group at week 13 and in 26 (38%; 26·7-50·8) and 42 (60%; 47·6-71·5) patients at week 25, respectively. After a median follow-up of 19·8 months (IQR 12·8-25·7), median overall survival was not reached in the nivolumab followed by ipilimumab group (95% CI 23·7-not reached), whereas over a median follow-up of 14·7 months (IQR 5·6-23·9) in the ipilimumab followed by nivolumab group, median overall survival was 16·9 months (95% CI 9·2-26·5; HR 0·48 [95% CI 0·29-0·80]). A higher proportion of patients in the nivolumab followed by ipilimumab group achieved 12-month overall survival than in the ipilimumab followed by nivolumab group (76%; 95% CI 64-85 vs 54%; 42-65). Nivolumab followed by ipilimumab appears to be a more clinically beneficial option compared with the reverse sequence, albeit with a higher frequency of adverse events. Bristol-Myers Squibb.


[Age-related features of protein synthesis rhythm in hepatocytes. Effects of extracellular medium].
Cell interactions have been studied in cultures pf hepatocytes from young and old rats. The rhythm of protein synthesis is an index of cell interaction and synchronization in culture, while the amplitude of oscillations characterized cell cooperation in an aggregate rhythm. The mean rhythm amplitude in the culture of hepatocytes from old rats is twice lower than that from young rats. Gangliosides (mixture, bovine brain gangliosides) and alpha1-adrenomimetic phenylephrine enhanced synchronization of cultures of the cells from old rats and increased the amplitude of oscillations to the level of young animals. Addition of rat blood serum (10%) to the medium revealed the rhythm of protein synthesis in the culture, asynchronous in the control, i.e., led to their synchronization. In media with young and old rat blood sera, oscillations were intense, with high amplitudes, and low, respectively. Addition of bovine brain gangliosides to a medium with old rat blood serum increased the amplitudes of oscillations to a level of the rhythm stimulated by the young rat serum. Thus, the cells of old animals can fully perceive synchronizing factors and, in the case of their increased concentration, the rhythm of protein synthesis in old animals did not differ from that in young rats. Current data on biochemical mechanisms underlying intercellular cooperation in the formation of population rhythm of protein synthesis have been discussed.


CircPDE4B inhibits retinal pathological angiogenesis via promoting degradation of HIF-1α though targeting miR-181c.
Retinopathy of prematurity is a major cause of childhood blindness worldwide. Hence, exploring the proper treatment methods is a must in tacking this disease. qRT-PCR and western blot were used to detect the expression of genes and proteins, respectively. The proliferation of human retinal vascular endothelial cells (HRECs) was ensured by MTT assay. The luciferase activity was measured through luciferase assay. The inverted phase-contrast light microscope was used to observe the formation of a vascular tube. In the present study, our data demonstrated that circPDE4B was downregulated, while hypoxia-inducible factor-1α (HIF-1α) and VEGFA were upregulated in the retinopathy of prematurity model in vitro and in vivo. CircPDE4B increasing remarkably inhibited the expression of HIF-1α and VEGFA in hypoxia-induced HRECs and subsequent repressed cell proliferation and pathological angiogenesis. We further found that miR-181c suppressed the expression of von Hippel-Lindau (VHL), while circPDE4B could promote VHL expression via binding to miR-181c. Finally, our results revealed that circPDE4B inhibited the expression of VEGFA and pathological angiogenesis via facilitating VHL-mediated ubiquitin degradation of HIF-1α. In conclusion, circPDE4B suppressed the expression of VEGFA and pathological angiogenesis via promoting VHL-mediated ubiquitin degradation of HIF-1α through binding to miR-181c. Our study indicated that circPDE4B might be an effective therapeutic target of retinopathy of prematurity.


Surfen-Assembled Graphene Oxide for Fluorescence Turn-On Detection of Sulfated Glycosaminoglycans in Biological Matrix.
Sulfated glycosaminoglycans (GAGs) not only serve as a biomarker for mucopolysaccharidoses disease but also participate in various biological processes, such as blood clot medication (heparin) and signal transduction (heparan sulfate). However, few fluorescent sensors, such as 1,9-dimethylmethylene blue, have been developed for the detection of sulfated GAGs in the real world. Herein, we fabricated a surfen/few-layer graphene oxide (FLGO) nanocomplex for sensing sulfated GAGs in biological fluids. Surfen molecules are self-assembled onto the surface of FLGO through electrostatic attraction, and their fluorescence was then quenched by the creation of the FLGO-surfen complex (static quenching) and partially combined with the energy transfer from surfen to FLGO (dynamic quenching). The presence of sulfated GAGs resulted in the fluorescence recovery through the formation of the surfen-GAGs complex, which exhibits weak binding to FLGO and keeps surfen molecules away from the FLGO surface. Because FLGO efficiently reduced the fluorescence background from surfen and competed with sulfated GAGs for binding to surfen, surfen-assembled FLGO exhibited higher sensitivity and better selectivity for sulfated GAGs than surfen. The strategy mentioned above was exemplified by the analysis of heparin in human plasma and sulfated GAGs in an artificial cerebrospinal fluid; the limits of detection at a signal-to-noise ratio of 3 for heparin, dermatan sulfate, and heparin sulfate were determined to be 30, 30, and 60 ng/mL, respectively.


Efficient Maximum Likelihood Estimation for Pedigree Data with the Sum-Product Algorithm.
We analyze data sets consisting of pedigrees with age at onset of colorectal cancer (CRC) as phenotype. The occurrence of familial clusters of CRC suggests the existence of a latent, inheritable risk factor. We aimed to compute the probability of a family possessing this risk factor as well as the hazard rate increase for these risk factor carriers. Due to the inheritability of this risk factor, the estimation necessitates a costly marginalization of the likelihood. We propose an improved EM algorithm by applying factor graphs and the sum-product algorithm in the E-step. This reduces the computational complexity from exponential to linear in the number of family members. Our algorithm is as precise as a direct likelihood maximization in a simulation study and a real family study on CRC risk. For 250 simulated families of size 19 and 21, the runtime of our algorithm is faster by a factor of 4 and 29, respectively. On the largest family (23 members) in the real data, our algorithm is 6 times faster. We introduce a flexible and runtime-efficient tool for statistical inference in biomedical event data with latent variables that opens the door for advanced analyses of pedigree data.


Determination of the predictive factors of long-lasting insecticide-treated net ownership and utilisation in the Bamenda Health District of Cameroon.
Malaria is a serious health concern in Africa. In Cameroon, an endemic country where malaria remains a major public health problem, several control measures have been put in place among which the use of insecticide-treated bednets (LLINs/ITNs) is considered one of the core vector control strategies. However, the greatest challenges include ownership and utilisation by individuals and households. Factors such as age, marital status, gender, education and occupation of the household head, household size, knowledge of bednets, socioeconomic status, and environmental factors have been suggested to have an impact on bednet ownership and utilisation in different settings. The present study sought to determine bednet ownership and utilisation rates and to assess the impact of predictive factors on bednet ownership and use in the Bamenda Health District (BHD) of Cameroon. A cross-sectional study involving 384 households was conducted in six health areas in the BHD. A structured and semi-structured questionnaire was used to collect data on demographic and household characteristics as well as information on their bednet ownership and utilisation. Descriptive statistics, bivariate and multivariate logistic regression analysis were performed. Frequency of bednet ownership was relatively high (63.5%) with LLINs being most abundant (91.9%); the majority of households (87.7%) obtained their bednets during the 2011 free distribution campaign. Utilisation was relatively high (69.3%), with negligence (29.3%) and heat discomfort (26.7%) accounting most for non-usage of bednets. Children less than 5 years (63%) and pregnant women (60%) most often used these nets. Households headed by a married couple, those with older household heads, household with smaller size (5-12 persons), and knowledge of bednets (good knowledge) had positive impacts on bednet ownership (p < 0.05). The gender of the household head (males), their educational level, environmental conditions (presence of suitable mosquito breeding sites), bednet number in households (greater number of bednets) and the prioritised groups (children < 5 and pregnant women) had positive impacts on bednet utilisation in households (p < 0.05). There was a negative association between bednet ownership and utilisation by households as bednet ownership was high and utilisation of these nets was low. Marital status and age of household head, household size, and knowledge of bednets had impacts on bednet ownership while gender and educational level of the household head, environmental suitability, the number of bednets and the two prioritised groups had an impact on bednet usage. These factors may be relevant for policy makers and in decision making for the intensification of campaign strategies to ensure more effective subsequent distribution campaigns in the BHD and beyond.


Nutritional aspects of night eating and its association with weight status among Korean adolescents.
A growing body of research has indicated that night eating could be associated with poor diet quality and negative health outcomes. This study examined the nutritional aspects of night eating, its related factors, and the association between night eating and body weight among Korean adolescents. This study analysed the data from a one day 24-hour dietary recall as well as a demographic survey of 1,738 Korean adolescents aged 12 to 18-years-old obtained from the 2010-2012 Korea National Health and Nutrition Examination Survey. 'Night eating' was defined as consuming 25% or more of one's daily energy intake between 21:00 and 06:00. Subjects complying with the preceding condition were classified as 'night eaters', whereas the rest were considered 'non-night eaters'. Logistic regression analysis examined factors related to night eating. Multiple linear regression analyses were used to examine the relationship between night eating and BMI z-scores, whereas multinomial logistic regression analysis was used to examine the relationship between night eating and weight status. About 21% of Korean adolescents appeared to be night eaters. Night eaters showed increased breakfast skipping (P = 0.001), higher energy intake from snacks (P < 0.001), greater proportion of energy intake from fat (P = 0.029), and lower Dietary Diversity Scores (P = 0.008) than non-night eaters. Male adolescents presented 1.9 times higher odds of being night eaters than females. Adolescents whose both parents were night eaters were 4.4 times as likely to be night eaters as those whose neither parents were. Female adolescents showed a significant relationship between night eating and BMI z-scores (β = 0.28, P = 0.004). However, night eating did not increase odds of being overweight or obese in adolescents. Night eating in Korean adolescents was related to undesirable dietary behaviours and low diet quality in general as well as higher BMI z-scores in females. Male gender and parental night eating appeared to be the factors that significantly increased odds of night eating. These results suggest that night eating should be considered when designing nutrition education or intervention programs targeting adolescents.


Roles of p38 MAPK in the regulation of the inflammatory response to swine influenza virus-induced acute lung injury in mice.
Swine influenza virus (SIV), one of the most important zoonotic agents, is associated with major public health concerns. The current study was conducted to investigate the role of p38 mitogen-activated protein kinase (p38 MAPK) in the regulation of the inflammatory response to acute lung injury (ALI) induced by SIV of H9N2 subtype (H9N2-SIV) in mice. For this purpose, BALB/c mice were intranasally infected with 20 LD(50) of H9N2-SIV (infected group), while non-infected mice served as control (control group). To assess the effect of p38 MAPK, its specific inhibitor SB203580 was employed followed by SIV infection (SB group). At various times after infection, mouse lungs were subjected to pathological and histological observations and detection of inflammatory cytokines tumor necrosis factor α (TNF)-α, interleukin (IL)-1β, IL-6, and IL-10 and phosphorylated p38 MAPK. The obtained results showed obvious inflammatory responses, injury and raised levels of inflammatory cytokines and phosphorylated p38 MAPK in the lungs of virus-infected mice. In the mice inoculated with the virus alone, the level of phosphorylated p38 MAPK increased from day 2 and peaked at day 6 post infection (p.i.). However, SB203580 caused lower increases in inflammatory cytokines and phosphorylated p38 MAPK and a milder lung injury. These findings indicate that the activation of p38 MAPK upregulated the inflammatory responses to H9N2-SIV-induced ALI, increased its severity and promoted the production of inflammatory cytokines.


Protective effects of bendazac lysine on diabetic peripheral neuropathy in streptozotocin-induced diabetic rats.
1. Diabetic neuropathy is a many faceted complication of both type I and II diabetes. The aim of the present study was to investigate the effects of bendazac lysine (BDL), an anticataract drug, on experimental diabetic peripheral neuropathy (DPN) in rats. 2. Diabetes was induced in rats by intraperitoneal injection of 75 mg/kg streptozotocin (STZ) dissolved in 0.1 mol/L citrate buffer (pH 4.4). Bendazac lysine was administered to rats at doses of 50, 100 and 200 mg/kg twice a day for 12 weeks. 3. Diabetic rats without treatment showed hypopraxia, polydipsia, polyuria, slow weight gain, cataract, increased tail-flick threshold temperature, decreased motor nerve conduction velocity (nd induced pathological morphological changes of myelinated nerve fibres. All these symptoms were ameliorated in diabetic rats treated with BDL. Bendazac lysine ameliorated the blood glucose concentration, glycosylated haemoglobin levels and insulin levels in the plasma of diabetic rats, reduced aldose reductase activity in erythrocytes and advanced glycation end-products in both nerves and serum and increase the activity of glutathione peroxidase in the nerves and Na(+)/K(+)-ATPase in the nerves and erythrocytes. 4. Bendazac lysine exerts its protective effects against the progression of diabetic peripheral neuropathy in STZ-diabetic rats through multiple mechanisms and is a potential drug for the prevention of deterioration in DPN.


Inherent rheology of a granular fluid in uniform shear flow.
In contrast to normal fluids, a granular fluid under shear supports a steady state with uniform temperature and density since the collisional cooling can compensate locally for viscous heating. It is shown that the hydrodynamic description of this steady state is inherently non-Newtonian. As a consequence, the Newtonian shear viscosity cannot be determined from experiments or simulation of uniform shear flow. For a given degree of inelasticity, the complete nonlinear dependence of the shear viscosity on the shear rate requires the analysis of the unsteady hydrodynamic behavior. The relationship to the Chapman-Enskog method to derive hydrodynamics is clarified using an approximate Grad's solution of the Boltzmann kinetic equation.


The functional connectivity of intralaminar thalamic nuclei in the human basal ganglia.
Projections of the centromedian-parafasicularis neurons of the intralaminar thalamus are major inputs of the striatum. Their functional role in the activity of human basal ganglia (BG) is not well known. The aim of this work was to study the functional connectivity of intralaminar thalamic nuclei with other BG by using the correlations of the BOLD signal recorded during "resting" and a motor task. Intralaminar nuclei showed a marked functional connectivity with all the tested BG, which was observed during "resting" and did not change with the motor task. As regards the intralaminar nuclei, BG connectivity was much lower for the medial dorsal nucleus (a thalamic nucleus bordering the intralaminar nuclei) and for the default mode network (although intralaminar nuclei showed a negative correlation with the default mode network). After the "regression" of intralaminar nuclei activity (partial correlation), the functional connectivity of the caudate and putamen nuclei with other BG decreased (but not with the primary sensorimotor cortex). Present data provide evidence that intralaminar nuclei are not only critical for striatal activity but also for the global performance of human BG, an action involving subcortical BG loops more than cortico-subcortical loops. The high correlation found between BG suggest that, similarly to that reported in other brain centers, the very-slow frequency fluctuations are relevant for the functional activity of these centers.


Inbreeding among some Brahman populations of Tamil Nadu.
A statewide survey of four endogamous Brahman populations of Tamil Nadu reveals a low level of inbreeding in three of them. In the fourth population, the Thengalai, the level is higher, but not as high as in other social castes. The Tamil Brahmans rank next to the Telugu and the Kanarese Brahmans in this respect. Uncle-niece marriages also occur as in Telugu-speaking populations, and these exceed in the two Ayyangar populations in comparison to the Ayyar. A decline of first-cousin marriages and an increase of uncle-niece marriages are detected in the first two living generations in each population.


Hyperthyroidism complicating pregnancy: results of treatment by antithyroid drugs in 77 pregnancies.
Seventy-seven pregnancies (79 infants) complicated by hyperthyroidism were seen at three Dublin Maternity Hospitals during a 25 year period. Hyperthyroidism was diagnosed following conception in 14 pregnancies. Treatment was with carbimazole alone in 73 pregnancies, in a usual dose of 5 to 10 mg daily. The total fetal loss was 15.2 per cent with a perinatal loss of 5.1 per cent. The perinatal loss in patients treated with carbimazole alone was 4.1 per cent (excluding one death due to congenital malformation). Four infants (5.1 per cent) had goitre and 57 (85.1 per cent) of the surviving infants were above the 25th centile for gestational age. Spontaneous premature labour occurred in 7 pregnancies (9.1 per cent). There was a relative excess of infants with a birth weight less than the 25th centile, of neonatal goitre and premature labour after pregnancy in which treatment was started following conception. Hyperthyroidism complicating pregnancy can be treated effectively with antithyroid drugs given alone and in the minimal effective dose.


Patterns and importance of self-other differences in college drinking norms.
College students overestimate other students' drinking behavior (descriptive norms) and attitudes (injunctive norms). This study explored the effects of demographics, norm type, and reference group on the magnitude of self- other differences (SODs). Participants (N = 1,611; 64% women) completed surveys assessing demographics, drinking patterns, and perceived norms. A subset of 122 students provided consumption data 1 month later to test predictors of changes in drinking. Overall, women and non-Greeks (Greek = member of fraternity or sorority) reported larger SODs for both norm types compared with men and Greeks. Heavier drinkers reported smaller SODs. Gender x Reference Group interactions revealed that women had larger SODs for reference groups increasingly distal to them; for men, the largest SODs occur for close friends versus more distal groups. Larger SODs for descriptive norms predicted increases in drinking, consistent with social norms theory.


Surgical treatment of pulmonary arteriovenous malformations.
Pulmonary arteriovenous malformations (PAVMs) are direct communications between the branches of pulmonary arteries and veins. This study evaluates surgically treated cases of pulmonary arteriovenous malformations. We retrospectively examined 41 cases of PAVM that were operated in our clinic between 1995 and 2012. We obtained the clinical, radiological, and surgical data of the patients from their files. The 41 cases comprised 27 males and 14 females. Their mean age at diagnosis was 39.8 years (range: 9-71). The symptoms were hemoptysis in 28 cases, dyspnea in five, cough in three, and epistaxis in two; three patients were asymptomatic. Twenty-three right and 19 left posterolateral thoracotomies were performed, including one case which was operated bilaterally. Lower lobectomy was performed in 17 patients, lower lobectomy and lingulectomy in two, upper lobectomy in ten, middle lobectomy in two, segmentectomy in seven, and wedge resection in four. Postoperative histopathology was arteriovenous malformation in all cases. PAVMs are rare clinical conditions. Surgery remains the first choice when embolization treatment cannot be performed or is not successful, in symptomatic and complicated patients with PAVM, and/or in cases where the PAVM diagnosis cannot be established.


A Child is Being Caged: Resignation Syndrome and the Psychopolitics of Petrification.
Uppgivenhetssyndrom, or resignation syndrome (RS), is a disorder that until recently was thought to affect the children of refugees in Sweden alone. The heuristic of psychopolitics is used to theorize RS as a form of abjection (Bataille, Kristeva) and petrification (Fanon, Marriott), and the movement from petrification to petrification in hallucinosis (Fanon, Bion) is delineated: first these children are petrified by persecutory and culturally specific stereotypes that precede and exceed them symbolically, and then, through a succession of shocks, they enter a post-traumatic stupor in which the faltering symbolization of the stereotype gives way to the (dis)embodiment of abject thinghood. Marriott's distinction between mirror as mask and mask as mirror allows the attribution of RS not only to sociocultural mimesis and the psychosocial impact of stereotypes (mirror as mask) but also to a socially imposed absence that the stereotype simultaneously conceals and reveals (mask as mirror). RS (petrification in hallucinosis) is considered the (dis)embodiment of this socially imposed absence.


Maximal Efficiency of PSII as a Marker of Sorghum Development Fertilized With Waste From a Biomass Biodigestion to Methane.
The aim of experiments was to investigate a maximal efficiency of PSII, as a marker indicating growth, vigor, energetic value and physiological activity of sorghum fertilized with wastes from a biomass biodigestion to methane in a distillery integrated with a biogas plant using corn grains as substrate. The sorghum plants grown outdoor in different climate and in pots and in field were fertilized with different doses of the waste or Apol-humus - a soil improver and Stymjod - a nano-organic-mineral fertilizer. The maximal efficiency of PSII, in comparison with plant growth and health, chlorophyll content, gas exchange, activity of selected enzymes, element content in leaves and energetic value were studied. The wastes applied to soil resulted in increased maximal efficiency of PSII and the doses of 30 m3 ha-1 and 40-50 m3 ha-1 of the non-centrifuged and centrifuged ones, respectively, were most efficient. This enhancement was associated with the increased kinetics of plant growth, their health, fresh and dry biomass and physiological activity of plants as evidenced by activity of acid and alkaline phosphatase, RNase and dehydrogenase, as well as by gas exchange: net photosynthesis, transpiration, stomatal conductance, intercellular CO2 concentration and index of chlorophyll content in leaves. The fertilization with Apol-humus and Stymjod additionally increased maximal photochemical efficiency of PSII and plant development, biomass yield and physiological activity. The results indicate that waste from a biomass biodigestion to methane can be used as a natural fertilizer in sorghum crops and this ensures their recycling and environmental protection. The measurement values of maximal efficiency of PSII were proportionally to the vigor, growth and physiological activity of the plants. The obtained results indicate that the maximal efficiency of PSII in sorghum plants is a non-destructive method for defining the degree of growth and may be used as a marker of plant vigor and health, development and physiological activity expressed by gas exchange and activity of selected enzymes.


[Free functional muscle transplantation for facial reanimation: experimental comparison between the one- and two-stage approach].
To investigate functional results of either one- or two-staged free muscle transplantation, the scutuloauricularis model in the New Zealand white rabbits was used. 30 rabbits were divided into 2 groups with 15 animals each. In group 1 (one-stage approach) the peroneus brevis (PB) muscle was harvested as a free muscle graft with a 7-cm long motor branch. The graft was positioned in the place of the right scutuloauricularis (SCUT) and its vascular supply microsurgically re-established. The motor branch was transferred to the contralateral side and its proximal end coapted to the cut facial motor branch to the left SCUT. Before nerve coaptation, biopsies were harvested from the cut motor branch for morphological analysis. In group 2 (two-stage approach) a 7-cm long saphenous nerve graft was taken and coapted to the cut motor branch of the SCUT and crossed over to the contralateral side. Nerve specimens from the cut motor branch were taken. Eight months later, free transplantation of the PB was performed and its motor branch coapted to the distal end of the cross-over nerve graft. After a total time period of 13 months the final experiments were carried out in each group. Maximal tetanic tensions in the reinnervated PB were measured and biopsies of muscle grafts together with nerve biopsies from the distal part of the motor branch were harvested for morphological analysis. Muscle grafts of group 1 revealed tetanic tension values of 12.5 N (SD 3.1) in comparison to 10.6 N (SD 3.5) obtained in group 2. This difference was not statistically significant (p = 0.303). In group 1 the amount of regenerated nerve fibres counted at the distal motor branch site (mean: 2798, SD 1242) was significantly higher (p = 0.008) than in group 2 (mean: 1138, SD 1004). Muscle graft morphology revealed significantly less type I fibres (p = 0.016) and more type II b/d fibres (p = 0.011) in group 1 compared to group 2. However, the overall amount of perimysial connective tissue showed no significant difference in both groups (p = 0.478). Free muscle transplantation in a one-stage approach offers similar functional results in comparison to the two-stage approach. Although muscle grafts of the one-stage transplantation underwent a longer period of denervation, similar contents of perimysial connective tissue could be observed.


Predictive chemometric modeling of DPPH free radical-scavenging activity of azole derivatives using 2D- and 3D-quantitative structure-activity relationship tools.
The endogenous antioxidants often fail to manage the systemic free radical overload resulting from extensive exposure to environmental pollutants and improper diet. Such free-radical burden over a prolonged period leads to oxidative stress, which in turn, promotes an array of fatal diseases. Five different in silico methodologies have been employed here for a series of azole derivatives, which identify the essential structural attributes of the molecules and quantify the contributions of the prime molecular prerequisites for designing compounds with improved antioxidant activity. The importance of the different constituents is quantitatively analyzed using the descriptor-based quantitative structure-activity relationship and group-based quantitative structure-activity relationship models while the pharmacophore, comparative molecular similarity index analysis and hologram quantitative structure-activity relationship models serve as essential query tools for screening of azole compounds in order to select potent antioxidant molecules.