Vital signs on hospital discharge and re admission rates.
Assessing the stability of a patient's vital signs in the 24 hours before discharge has been suggested as an objective and inexpensive way to determine safety for discharge. To determine the association between unstable vital signs at the time of discharge with the readmission rate over a one-year period. An observational cohort multi-center study at three urban community hospitals using electronic health record data collected from November 1, 2016, to October 30, 2017. A total of 29322 hospitalizations to medical floors with complete sets of vital signs were included. The final vital signs collected on the day of discharge were used for analysis. The readmission rates were compared using different variables such as age, sex, insurance payer (Medicare or Medicaid), discharge time, discharge disposition, length of stay at the hospital, the number, and type of abnormal vital signs at discharge. Unstable vital signs at discharge were found in 2862 patients (9.8%). The readmission rate was highest in patients with two (11.3%) unstable vital signs compared to those with one (8.5%) and three or more (0%) instabilities. Patients with a combination of heart rate >100 beats/min and respiratory rate >20 breaths/min at discharge had a 14.1% seven-day readmission rate (P = 0.0057, Odds Ratio = 1.87, Confidence Interval = 1.19-2.95). Vital sign instabilities in the 24 hours before discharge are associated with increased seven-day readmission rate.


Long-Lasting Insecticide-Treated Nets Combined or Not with Indoor Residual Spraying May Not Be Sufficient to Eliminate Malaria: A Case-Control Study, Benin, West Africa.
In sub-Saharan Africa, despite the implementation of multiple control interventions, the prevalence of malaria infection and clinical cases remains high. The primary tool for vector control against malaria in this region is the use of long-lasting insecticide-treated nets (LLINs) combined or not with indoor residual spraying (IRS) to achieve a synergistic effect in protection. The objective of this study was to assess the effectiveness of LLINs, with or without IRS, protected against Plasmodium falciparum infection and uncomplicated clinical cases (UCC) of malaria in Benin. A case-control study was conducted, encompassing all age groups, in the urban area of Djougou and the rural area of Cobly. A cross-sectional survey was conducted that included 2080 individuals in the urban area and 2770 individuals in the rural area. In the urban area, sleeping under LLINs did not confer significant protection against malaria infection and UCC when compared to no intervention. However, certain neighbourhoods benefited from a notable reduction in infection rates ranging from 65% to 85%. In the rural area, the use of LLINs alone, IRS alone, or their combination did not provide additional protection compared to no intervention. IRS alone and LLINs combined with IRS provided 61% and 65% protection against malaria infection, respectively, compared to LLINs alone. The effectiveness of IRS alone and LLINs combined with IRS against UCC was 52% and 54%, respectively, when compared to LLINs alone. In both urban and rural areas, the use of LLINs alone, IRS alone, and their combination did not demonstrate significant individual protection against malaria infection and clinical cases when compared to no intervention. In the conditions of this study, LLINs combined or not with IRS are not effective enough to eliminate malaria. In addition to the interventions, this study identified factors associated with malaria in Benin as housing design, neglected social groups like gender-marginalised individuals and adolescents, and socio-economic conditions acting as barriers to effective malaria prevention. Addressing these factors is crucial in order to facilitate malaria elimination efforts in sub-Saharan Africa.


Cromolyn sodium for ACE inhibitor-induced cough.
There are several theories on the cause of ACE inhibitor-induced cough, but the exact mechanism is not known. In many patients, if cough develops, the ACE inhibitor can be discontinued and a drug in another therapeutic class used in its place. However, in patients with CHF, diabetic nephropathy, and patients who have experienced a myocardial infarction, discontinuing the ACE inhibitor may not be in the best interest of the patient. In this patient population it would be reasonable to try cromolyn sodium to treat cough, while continuing the ACE inhibitor. Data are not available to support the efficacy of cromolyn sodium to treat cough in patients with diabetic nephropathy, but these patients clearly benefit from the use of an ACE inhibitor. Other factors not addressed in the case reports and the clinical trial such as patient adherence, cost, and quality of life should also play a role in the decision to use cromolyn sodium. Cromolyn sodium has been effective for the treatment of ACE inhibitor-induced cough in many case reports and has had mild success in one small clinical trial. Although none of the reports adequately assessed adverse effects, studies examining cromolyn for other indications have demonstrated a relatively benign adverse effect profile. It is difficult to recommend an exact dose to use because of the dosing variability in the case reports. The majority of the case reports and the one clinical trial used dosages similar to recommendations for bronchial asthma (i.e., 2 puffs [1.6 mg] 4 times daily via MDI or 20-mg capsules 4 times daily via breath-activated inhalation). At this time, the use of cromolyn sodium is a viable option, but more controlled studies are needed to fully elucidate its role in the treatment of ACE inhibitor-induced cough.


Oxidative stress and the mitochondrial theory of aging in human skeletal muscle.
According to the mitochondrial theory of aging, an age-related increase in oxidative stress is responsible for cellular damage and ultimately cell death. Despite compelling evidence that supports the mitochondrial theory of aging in some tissues, data regarding aging skeletal muscle are inconsistent. We collected resting muscle biopsies from the vastus lateralis, and 24 h urine samples from, young (N = 12, approximately 22 yr), and older (N = 12 approximately 72 yr) men. Urinary 8-OHdG was significantly higher in older as compared to younger men (Old: 7714 +/- 1402, Young: 5333 +/- 1191 ng g(-1) creatinine: p = 0.005), as were levels of protein carbonyls (Old: 0.72 +/- 0.42, Young: 0.26 +/- 0.14 nmol mg(-1) protein: p = 0.007). MnSOD activity (Old: 7.1 +/- 0.8, Young: 5.2 +/- 1.8 U mg(-1) protein: p = 0.04) and catalase activity (Old: 8.5 +/- 2.0, Young: 6.2 +/- 2.4 micro mol min(-1) mg(-1) protein: p = 0.03) were significantly higher in old as compared to young men, respectively, with no differences observed for total or CuZnSOD. Full-length mtDNA appeared lower in old as compared to young men, and mtDNA deletions were present in 6/8 old and 0/6 young men (p = 0.003). The maximal activities of citrate synthase, and complex II+III, and IV were not different between young and old men, however, complex I+III activity was marginally higher in older as compared to younger men (Old: 2.5 +/- 0.5, Young: 1.9 +/- 0.5 micromol min(-1) g(-1) w.w: p = 0.03) respectively. In conclusion, healthy aging is associated with oxidative damage to proteins and DNA, a compensatory up-regulation of antioxidant enzymes, and aberrations of mtDNA, with no reduction in electron transport chain maximal enzyme activity.


Pneumococcal zinc metalloproteinase ZmpC cleaves human matrix metalloproteinase 9 and is a virulence factor in experimental pneumonia.
The ZmpC zinc metalloproteinase of Streptococcus pneumoniae, annotated in the type 4 genome as SP0071, was found to cleave human matrix metalloproteinase 9 (MMP-9). The previously described IgA protease activity was confirmed to be specifically linked to the IgA1-protease/SP1154 zinc metalloproteinase. MMP-9 is a protease cleaving extracellular matrix gelatin and collagen and is activated by proteolytic cleavage like most proteases. MMP-9 is a human protease and is involved in a variety of physiological and pathological matrix degrading processes, including tissue invasion of metastases and opening of the blood-brain barrier. While TIGR4 (serotype 4) and G54 (serotype 19) pneumococcal genome strains have a highly conserved copy of zmpC, the genome of R6 (a derivative of serotype 2 D39 strain) lacks zmpC. Both the analysis for zmpC presence and MMP-9 cleavage activity in various pneumococcal strains showed correlation of ZmpC with MMP-9 cleavage activity. When assaying clinical isolates of S. pneumoniae, the zmpC gene was not found in any of the nasal and conjunctival swab isolates, but it was present in 1 out of 13 meningitis isolates and in 6 out of 11 pneumonia isolates. In a murine pneumonia model, infection with a zmpC-mutant reduced mortality at 3-4 days post-infection by 75%, when compared with infection with wild-type strains. These data indicate that the ZmpC pneumococcal protease may play a role in pneumococcal virulence and pathogenicity in the lung.


Lessons learned from two consecutive cleft lip and palate missions and the impact of patient education.
Two consecutive cleft missions were conducted in Guwahati, northeastern India in December 2010 and January 2011. In the later mission, a standardized patient education program for postoperative care was introduced. The objective of this study was to retrospectively evaluate the impact of the patient education program on cleft lip complications in terms of wound infection and dehiscence. Two hundred ninety-eight cleft lip repairs were performed in the first mission and 220 (74%) returned for early follow-up. In the second mission, 356 patients were operated on and 252 (71%) returned for follow-up. From the first mission, 8 patients (3.7%) were diagnosed with lip wound infection and 21 patients (9.6%) with lip dehiscence. After the second mission, only 1 patient (0.4%) returned with a wound infection and 16 (6.4%) were diagnosed with dehiscence.Using binary logistic regression including age, cleft type, postoperative antibiotics, surgeon, and patient education program as covariates, the patient education program stood out as the only variable with a statistically significant impact on the incidence of postoperative wound infections. Even though the incidence of lip dehiscence was reduced by one third when the patient education program was utilized, our regression model singled out the surgeons as the only factor significantly related to this type of complication. Moreover, no benefits of postoperative antibiotic prophylaxis were found. Further analysis of the data also implied that the use of tissue adhesive as a compliment to sutures does not reduce the risk of dehiscence.


Differences in awareness of and willingness to use pre-exposure prophylaxis and anticipated condom use among serodiscordant couples in Taiwan.
Pre-exposure prophylaxis (PrEP) has proven to be effective in reducing the risk of HIV transmission in uninfected individuals who engaged in sexual activity with HIV-infected partners. Serodiscordant couples are the key targets of PrEP implementation. The study aimed to compare awareness of and willingness to use PrEP and anticipated condom use among 112 HIV-serodiscordant couples: 32 heterosexuals couples, 70 men who have sex with men (MSM) couples, and 10 people who inject drugs (PWID) couples. A cross-sectional study was conducted in an AIDS designated hospital in Taiwan. The PrEP survey for discordant couples included questions on awareness of non-occupational post-exposure prophylaxis (nPEP) and PrEP, attitudes toward PrEP, anticipated condom use if using PrEP, and sexual behaviors. Overall, 46.2% were aware of PrEP, only 33% were willing to take PrEP, and 44.6% would continue condom use if they were taking PrEP. Among the three key populations, MSM couples had the highest awareness of and willingness to use PrEP. Awareness of and willingness to use PrEP did not differ by HIV status, with moderate agreement (Cohen's Kappa coefficient: 0.56) between HIV-serodiscordant partners. Both HIV-serodiscordant partners' willingness to use PrEP was significantly associated with being MSM (adjusted odds ratio (AOR), 4.28 [1.28-14.30], p = 0.018), previous receipt of nPEP (AOR, 6.98 [1.23-39.65], p = 0.028), anticipated condom use (AOR, 0.14 [0.05-0.41], p < 0.001), and income ≥ NT$30,000 per month (AOR, 2.25 (0.99-5.04), p = 0.05). Policy makers need to consider the differences among key populations to scale up PrEP implementation. More efforts should be focused on improving awareness of and willingness to use PrEP among heterosexual and PWID serodiscordant couples to scale up PrEP implementation in Taiwan.


Effects of dose and schedule of immune stimulant on efficacy of combination Corynebacterium parvum-cyclophosphamide treatment for a murine mammary adenocarcinoma.
Certain variables which might influence the outcome of combining cytotoxic drug and immune stimulant therapy were studied to optimize the effectiveness of Corynebacterium parvum combined with cyclophosphamide (CY) as treatment for a murine mammary adenocarcinoma (CaD2). Optimal effects of combined C. parvum-CY treatment in the CaD2 system were obtained when 443 to 1400 microgram of this immune stimulant per mouse were injected 2 to 3 days after CY chemotherapy and when combination treatment was continued on a weekly basis. The most critical factors contributing to the effectiveness of combination treatment in this system were the dose of C. parvum and the treatment frequency. The interval between chemotherapy and immune stimulant therapy was less critical to the outcome of combination treatment. Combination treatment given once or weekly significantly decreased tumor size in comparison to single or weekly CY treatment. A single treatment with CY and C. parvum significantly improved the survival over mice given a single CY treatment, but weekly CY and C. parvum treatment did not increase the survival over mice, given weekly chemotherapy.


Therapeutic evaluation of etanercept in a model of traumatic brain injury.
Antagonism of tumor necrosis factor-alpha with etanercept has proved to be effective in the treatment of spinal cord injury and centrally endotoxin-induced brain injury. However, etanercept may offer promise as therapy for traumatic brain injury (TBI). In this study, anesthetized rats, immediately after the onset of TBI, were divided into two major groups and given the vehicle solution (1 mL/kg of body weight) or etanercept (5 mg/kg of body weight) intraperitoneally once per 12 h for consecutive 3 days. Etanercept caused attenuation of TBI-induced cerebral ischemia (e.g., increased cellular levels of glutamate and lactate-to-pyruvate ratio), damage (e.g., increased cellular levels of glycerol) and contusion and motor and cognitive function deficits. TBI-induced neuronal apoptosis (e.g., increased numbers of terminal deoxynucleotidyl transferase αUTP nick-end labeling and neuronal-specific nuclear protein double-positive cells), glial apoptosis (e.g., increased numbers of terminal deoxynucleotidyl transferase αUTP nick-end labeling and glial fibrillary acidic protein double-positive cells), astrocytic (e.g., increased numbers of glial fibrillary acidic protein positive cells) and microglial (e.g., increased numbers of ionized calcium-binding adapter molecule 1-positive cells) activation and activated inflammation (e.g., increased levels of tumor necrosis factor-alpha, interleukin-1β and interleukin-6) were all significantly reduced by etanercept treatment. These findings suggest that etanercept may improve outcomes of TBI by penetrating into the cerebrospinal fluid in rats.


Magnetoencephalographic yield of interictal spikes in temporal lobe epilepsy. Comparison with scalp EEG recordings.
To compare magnetoencephalography (MEG) with scalp electroencephalography (EEG) in the detection of interictal spikes in temporal lobe epilepsy (TLE), we simultaneously recorded MEG and scalp EEG with a whole-scalp neuromagnetometer in 46 TLE patients. We visually searched interictal spikes on MEG and EEG channels and classified them into three types according to their presentation on MEG alone (M-spikes), EEG alone (E-spikes), or concomitantly on both modalities (M/E-spikes). The M-spikes and M/E-spikes were localized with MEG equivalent current dipole modeling. We analyzed the relative contribution of MEG and EEG in the overall yield of spike detection and also compared M-spikes with M/E-spikes in terms of dipole locations and strengths. During the 30- to 40-min MEG recordings, interictal spikes were obtained in 36 (78.3%) of the 46 patients. Among the 36 patients, most spikes were M/E-spikes (68.3%), some were M-spikes (22.1%), and some were E-spikes (9.7%). In comparison with EEG, MEG gave better spike yield in patients with lateral TLE. Sources of M/E- and M-spikes were situated in the same anatomical regions, whereas the average dipole strength was larger for M/E- than M-spikes. In conclusion, some interictal spikes appeared selectively on either MEG or EEG channels in TLE patients although more spikes were simultaneously identified on both modalities. Thus, simultaneous MEG and EEG recordings help to enhance spike detection. Identification of M-spikes would offer important localization of irritative foci, especially in patients with lateral TLE.


Endothelium-independent flow-induced dilation in the mouse carotid artery.
We investigated the locus of flow regulation of vascular tone in carotid arteries of C57 Bl/6 and eNOS(-/-) mice. Arterial segments (2-3 mm) were mounted in a perfusion myograph and preconstricted with 1 muM phenylephrine before monitoring flow-induced changes in lumen diameter. Both control and eNOS(-/-) mice demonstrated flow-dependent relaxation. This response was not attenuated by the NO synthase antagonist L-NAME, the cyclooxygenase inhibitor indomethacin, the selective guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxaline-1-one (ODQ), the adenylate cyclase inhibitor Rp-8-Br-cAMPs, integrin-binding RGD peptides, or by removal of the endothelium. Hypoxia, a physiological stimulus known to alter endothelium-dependent flow regulation of vascular tone, also failed to attenuate the observed flow-mediated dilation. These findings indicate the existence of a previously unidentified endothelium-independent mechanism of flow-induced dilation in the carotid artery. Further investigations to identify the mechanisms that underlie this response may provide novel therapeutic directions in the treatment of disorders characterized by abnormal flow regulation of vascular tone.


A complex gene locus enables xyloglucan utilization in the model saprophyte Cellvibrio japonicus.
The degradation of plant biomass by saprophytes is an ecologically important part of the global carbon cycle, which has also inspired a vast diversity of industrial enzyme applications. The xyloglucans (XyGs) constitute a family of ubiquitous and abundant plant cell wall polysaccharides, yet the enzymology of XyG saccharification is poorly studied. Here, we present the identification and molecular characterization of a complex genetic locus that is required for xyloglucan utilization by the model saprophyte Cellvibrio japonicus. In harness, transcriptomics, reverse genetics, enzyme kinetics, and structural biology indicate that the encoded cohort of an α-xylosidase, a β-galactosidase, and an α-l-fucosidase is specifically adapted for efficient, concerted saccharification of dicot (fucogalacto)xyloglucan oligosaccharides following import into the periplasm via an associated TonB-dependent receptor. The data support a biological model of xyloglucan degradation by C. japonicus with striking similarities - and notable differences - to the complex polysaccharide utilization loci of the Bacteroidetes.


P3DOCK: a protein-RNA docking webserver based on template-based and template-free docking.
The main function of protein-RNA interaction is to regulate the expression of genes. Therefore, studying protein-RNA interactions is of great significance. The information of three-dimensional (3D) structures reveals that atomic interactions are particularly important. The calculation method for modeling a 3D structure of a complex mainly includes two strategies: free docking and template-based docking. These two methods are complementary in protein-protein docking. Therefore, integrating these two methods may improve the prediction accuracy. In this article, we compare the difference between the free docking and the template-based algorithm. Then we show the complementarity of these two methods. Based on the analysis of the calculation results, the transition point is confirmed and used to integrate two docking algorithms to develop P3DOCK. P3DOCK holds the advantages of both algorithms. The results of the three docking benchmarks show that P3DOCK is better than those two non-hybrid docking algorithms. The success rate of P3DOCK is also higher (3-20%) than state-of-the-art hybrid and non-hybrid methods. Finally, the hierarchical clustering algorithm is utilized to cluster the P3DOCK's decoys. The clustering algorithm improves the success rate of P3DOCK. For ease of use, we provide a P3DOCK webserver, which can be accessed at www.rnabinding.com/P3DOCK/P3DOCK.html. An integrated protein-RNA docking benchmark can be downloaded from http://rnabinding.com/P3DOCK/benchmark.html. www.rnabinding.com/P3DOCK/P3DOCK.html. Supplementary data are available at Bioinformatics online.


Studies on thiamine diphosphate kinase (EC 220.127.116.11) from brewer's yeast: purification and some properties.
Radiometric and fluorescent methods for detection of thiamine triphosphate have been used to show the presence of thiamine diphosphate kinase activity in brewer's yeast and to determine optimal conditions for its manifestation. A method of enzyme purification has been developed which involves glycerol-EDTA solution extraction, heat treatment, 2-fold ammonium sulphate fractionation, Sephadex G-200 gel filtration and ion-exchange chromatography on Sephadexes CP-C-50 and QAE-A-25. The protein has been purified 2000-fold in a 19% yield. The isoelectric and isoionic points, the amino acid composition and the molecular weight have been determined. Hydrophobic amino acids and those responsible for alpha-helix formation of the protein globule are predominant. The isoelectric point, as calculated by the amino acid composition and found by the maximum of the changes in fluorescence, is 5.8. The isoionic point value is identical with the isoelectric point. Upon gel filtration thiamine diphosphate kinase is eluted as two protein peaks with molecular weights of 162,000 +/- 8,000 and 81,000 +/- 4,000. After treatment with urea or sodium dodecyl sulphate, the protein dissociates into subunits with molecular weights of 12,500 and 14,000. The purified enzyme has some properties typical of a dissociating enzyme system.


Malnutrition in women with rheumatoid arthritis is not revealed by clinical anthropometrical measurements or nutritional evaluation tools.
To evaluate diagnostic instruments for assessment of nutritional status in patients with rheumatoid arthritis (RA) in relation to objective body composition data. Study subjects include 60 in-ward patients (83% women, median age 65 years). Anthropometric measures and the nutritional tools Mini Nutritional Assessment (MNA), Subjective Global Assessment (SGA), Malnutrition Universal Screening Tool (MUST) and Nutritional Risk Screening tool 2002 (NRS-2002). Body composition was determined by dual-energy X-ray absorptiometry and fat-free mass index (FFMI; kg/m(2)) and fat mass index (FMI; kg/m(2)) were calculated. Mean body mass index (BMI) for RA women and men were 24.4 and 26.9 kg/m(2), respectively. Twelve per cent of the women and none of the few men had BMI<18.5 kg/m(2), that is, the cutoff value for malnutrition. FFMI indicated 52% of the women and 30% of the men to be malnourished. The sensitivity and specificity for BMI to detect malnutrition according to FFMI were 27 and 100%, whereas for arm muscle circumference the sensitivity was 36% and the specificity 89% and for triceps skin fold 43 and 93%, respectively. For MNA, sensitivity was 85% and specificity 39% and for SGA 46 and 82%. Both MUST and NRS-2002 had sensitivity of 45% and specificity of 19%. A large proportion of in-ward RA patients had reduced FFMI. Concurrent elevation of fat mass made BMI a non-reliable tool to detect malnutrition. Of the tested clinical evaluation tools, MNA might be used as a screening instrument, but because of its low specificity it should be followed by body composition determination.


[Autopsy and ill-defined cause of death in the state of São Paulo, Brazil].
To investigate the proportion of deaths with an ill-defined cause in the Brazilian state of São Paulo between 1980 and 2002, taking into account the influence of autopsies on this proportion. Data on the number of deaths were obtained from the Brazilian Ministry of Health. The communities of the state of São Paulo were divided into three groups: (1) municipalities with a service to verify the cause of death (and that may conduct an autopsy), (2) municipalities without a cause of death verification service, and (3) the region of Baixada Santista, which had an extremely large increase in the proportion of deaths from ill-defined causes between 1980 and 1995. The impact of autopsies on the proportion of deaths with an ill-defined cause was defined based on the classification made by the first physician evaluating the cause of death, that is, the physician who referred the case to the verification service for autopsy or who completed the death certificate without referring the case to the verification service. Deaths from external causes were excluded, since autopsy is mandatory in these cases. The following were evaluated: (1) proportion of cases classified by the first evaluating physician as having an ill-defined cause, (2) proportion of autopsies in relation to the total number of deaths (except from external causes), and (3) proportion of deaths classified as ill-defined by the first evaluating physician but explained by the autopsy. The proportion of deaths classified by the first evaluating physician as having an ill-defined cause increased over the 1980-2002 period in all three groups studied: the municipalities with a verification service, the municipalities without a verification service, and in the Baixada Santista region. For the state of São Paulo overall, the increase was almost 30% over that 1980-2002 period. For the 1998-2002 period, the average proportion of autopsies compared to the total number of deaths (except from external causes) was 21.2% in the municipalities with a verification service, 6.4% in the municipalities without a verification service, and 2.6% in Baixada Santista. The proportion of deaths in 1998-2002 initially classified as having an ill-defined cause but that was explained by autopsy was 92.9% in the municipalities with a verification service, 32.5% in the municipalities without a verification service, and 10.7% in Baixada Santista. The performance of autopsies accounts for the difference in proportional mortality with an ill-defined cause in the three groups of communities studied. The increase in the number of deaths classified as ill-defined by the first evaluating physician occurring in the state of São Paulo over the 1980-2002 period suggests an important decline in the quality of death certificates completed at that first level. More research should be done on the reasons for that change.


Assessing Serum Concentrations of 25-Hydroxy-Vitamin D in North-Western Italy.
Backgound: Most of the published studies on vitamin D levels in Italy have been performed in specific age- or disease- subgroups. Few data are available on the status of vitamin D in the adult general population. We report on vitamin D levels of a large sample of adults from North-Western Italy. Association with age, sex, and season is also evaluated. 13,110 cases (24% men, 76% women; median age 67 [interquartile range, IQR, 56-77] years old) were collected in the North-Eastern of Piedmont (Italy). 25-OH-vitamin D levels were measured by chemiluminescent immunoassay. Median total vitamin D level was 19.9 ng/ml (IQR 11.2-28.8 ng/ml) with up to 3,592 (27.4%) and 10,185 (77.7%) subjects respectively below 12 and 30 ng/ml. Vitamin D levels were significantly higher in women than in men (20.5 vs 18.1 ng/ml; p<0.001), in summer than in winter (21.4 vs 18.5 ng/ml; p<0.001), and in individuals aged ≤45years or 46-64 years than in those older than 65 years (20.3 and 21.3 vs 18.8 ng/ml). The lowest mean vitamin D levels were reported during the winter season by men aged ≥65 years (14.7 ng/ml) and 46-64 years (16.8 ng/ml). Multivariate analysis confirmed that age (p<0.001), sex (p=0.002), season (p<0.001) and their interaction (p=0.03) were independently associated to vitamin D concentrations. This study clearly shows that the majority of adult Italian population, living in a sunny and highly urbanized area of North-Western Italy, have an important deficiency in vitamin D. However, these data must be interpreted with caution if considering the lack of standardization of vitamin D assays.


The effect of drink price and next-day responsibilities on college student drinking: a behavioral economic analysis.
More than [3/4] of U.S. college students report a heavy drinking episode (HDE; 5 (for men) and 4 (for women) drinks during an occasion) in the previous 90 days. This pattern of drinking is associated with various risks and social problems for both the heavy drinkers and the larger college community. According to behavioral economics, college student drinking is a contextually bound phenomenon that is impacted by contingencies such as price and competing alternative reinforcers, including next-day responsibilities such as college classes. This study systematically examines the role of these variables by using hypothetical alcohol purchase tasks to analyze alcohol consumption and expenditures among college students who reported recent heavy drinking (N = 207, 53.1% women). The impact of gender and the personality risk factor sensation seeking (SS) were also assessed. Students were asked how many drinks they would purchase and consume across 17 drink prices and 3 next-day responsibility scenarios. Mean levels of hypothetical consumption were highly sensitive to both drink price and next-day responsibility, with the lowest drinking levels associated with high drink prices and a next-day test. Men and participants with greater levels of SS reported more demand overall (greater consumption and expenditures) than women and students with low SS personality. Contrary to our hypotheses women appeared to be less sensitive to increases in price than men. The results suggest that increasing drink prices and morning academic requirements may be useful in preventing heavy drinking among college students.


[The different vascular reactions of intact and ischemic brain to adrenergic exposures].
Electrical stimulation of the cervical sympathetic ganglion and norepinephrine increase the tonus of the cerebral vessels in intact animals. This points to the significant role of adrenergic mechanisms in regulation of blood circulation in the brain. Local ischemic affection of the brain removes the vasoconstrictor effects of stimulation of the cervical sympathetic ganglion and norepinephrine. Analysis by means of dihydroergotamine suggests that ischemia of the brain disturbs the property of alpha-adrenoceptors of the cerebral vessels to increase the tonus of the latter in response to adrenergic effects.


A recombinant H7N9 influenza vaccine with the H7 hemagglutinin transmembrane domain replaced by the H3 domain induces increased cross-reactive antibodies and improved interclade protection in mice.
Influenza A H7N9 virus is the latest emerging pandemic threat, and has rapidly diverged into three clades, demanding a H7N9 virus vaccine with broadened protection against unmatched strains. Hemagglutinin (HA)-based structural design approaches for stabilizing HA proteins have provided excitingly promising results. However, none of the HA-based structural design approaches has been applied to a recombinant replicative influenza virus. Here we report that our HA-based structural design approach is a first in the field to generate a recombinant replicative H7N9 virus (H7N9-53TM) showing broadened protection. The H7N9-53TM contains a replaced H3 HA transmembrane domain (TM) in its HA protein. In mice, the inactivated H7N9-53TM vaccine induced significantly higher HI titers, HA-specific IgG titers, and IFN-γ production than the corresponding H7N9-53WT inactivated virus vaccine containing wild-type HA. More excitingly, mice immunized with the H7N9-53TM showed full protection against homologous (H7N9-53) and interclade (H7N9-MCX) challenges with minimal weight loss, no detectable lung viral loads, and no apparent pulmonary lesions and inflammation, while mice immunized with the H7N9-53WT showed partial protection (only 60% against H7N9-MCX) with severe weight loss, detectable lung viral loads, and severe pulmonary lesions and inflammation. In summary, this study presents a better vaccine candidate (H7N9-53TM) against H7N9 pandemics. Furthermore, our HA-based structural design approach would be conceivably applicable to other subtype influenza viruses, especially the viruses from emerging pandemic and epidemic influenza viruses such as H5N1 and H1N1.


Cerebrofaciothoracic dysplasia: Four new patients with a recurrent TMCO1 pathogenic variant.
Biallelic loss of function variants in the TMCO1 gene have been previously demonstrated to result in cerebrofaciothoracic dysplasia (CFTD; MIM #213980). The phenotype of this condition includes severe intellectual disability, as well as distinctive craniofacial features, including brachycephaly, synophrys, arched eyebrows, "cupid's bow" upper lip, and microdontia. In addition, nonspecific skeletal anomalies are common, including bifid ribs, scoliosis, and spinal fusion. Only 19 molecularly confirmed patients have been previously described. Here, we present four patients with CFTD, including three brothers from a Pakistani background and an additional unrelated white Scottish patient. All share the characteristic craniofacial appearance, with severe intellectual disability and skeletal abnormalities. We further define the phenotype with comparison to the published literature, and present images to define the dysmorphic features in a previously unreported ethnic group. All of our patient series are homozygous for the same c.292_293del (p.Ser98*) TMCO1 pathogenic variant, which has been previously reported only in an isolated Amish population. Thus we provide evidence that CFTD may be more common than previously thought. The patients presented here further delineate the phenotypic spectrum of CFTD and provide evidence for a recurrent pathogenic variant in TMCO1.


Cochrane systematic reviews of Chinese herbal medicines: an overview.
our study had two objectives: a) to systematically identify all existing systematic reviews of Chinese herbal medicines (CHM) published in Cochrane Library; b) to assess the methodological quality of included reviews. We performed a systematic search of the Cochrane Database of Systematic Reviews (CDSR, Issue 5, 2010) to identify all reviews of CHM. A total of fifty-eight reviews were eligible for our study. Twenty-one of the included reviews had at least one Traditional Chinese Medicine (TCM) practitioner as its co-author. 7 reviews didn't include any primary study, the remaining reviews (n = 51) included a median of 9 studies and 936 participants. 50% of reviews were last assessed as up-to-date prior to 2008. The questions addressed by 39 reviews were broad in scope, in which 9 reviews combined studies with different herbal medicines. For OQAQ, the mean of overall quality score (item 10) was 5.05 (95% CI; 4.58-5.52). All reviews assessed the methodological quality of primary studies, 16% of included primary studies used adequate sequence generation and 7% used adequate allocation concealment. Of the 51 nonempty reviews, 23 reviews were reported as being inconclusive, while 27 concluded that there might be benefit of CHM, which was limited by the poor quality or inadequate quantity of included studies. 58 reviews reported searching a median of seven electronic databases, while 10 reviews did not search any Chinese database. Now CDSR has included large numbers of CHM reviews, our study identified some areas which could be improved, such as almost half of included reviews did not have the participation of TCM practitioners and were not up-to-date according to Cochrane criteria, some reviews pooled the results of different herbal medicines and ignored the searching of Chinese databases.


Refractory chronic GVHD emerging after splenectomy in a marrow transplant recipient with accelerated phase CML.
We report a 39-year-old female patient who underwent HLA-identical sibling allogeneic BMT for CML in accelerated phase. Severe pancytopenia refractory to G-CSF associated with progressive splenomegaly and RBC/platelet transfusion dependency were present from day +60 after BMT. MRD assessed by FISH and RT-PCR multiplex for BCR-ABL rearrangement was negative, and complete chimerism was documented by VNTR on days +100, +180, +360 and 2 years after BMT. Splenectomy was performed on day +225 and pancytopenia resolved but chronic extensive graft-versus-host disease developed, with hepatic cholestasis, diffuse scleroderma and sicca-like syndrome. She was sequentially and progressively treated with different immunosuppressive therapy combinations with no clear benefit. On day +940, she presented with infection over the previously present ulcers on both limbs, which culminated in septic shock and death on day +1041. We conclude that, although splenectomy may reverse poor graft function after allogeneic BMT, hyposplenism may trigger or worsen chronic extensive GVHD leading to increased morbidity and mortality.


Dietary medium-chain saturated fatty acids induce gene expression of energy metabolism-related pathways in adipose tissue of abdominally obese subjects.
Dietary medium-chain saturated fatty acids (MC-SFAs) have been shown to reduce total body fat. Previously, we showed that MC-SFAs prevent body fat accumulation, despite weight gain. Here, we aim to explore potential molecular mechanisms underlying the protective effect of MC-SFAs on body fat gain. The DairyHealth study examined the long-term effects of milk protein and milk fat with a low or high content of MC-SFA. In this 12 week, randomized, double-blind, diet intervention study, participants consumed 60 g milk protein (whey or casein) and 63 g milk fat (high MC-SFA or low MC-SFA) daily in a two by two factorial design. We used microarrays to measure whole genome gene expression changes in subcutaneous adipose tissue in a subpopulation of 12 participants, 6 in the low MC-SFA+casein group and 6 in the high MC-SFA+casein group. Gene expression of several genes that were found to be changed by MC-SFAs was confirmed in the full study population using qPCR. High MC-SFA resulted in an upregulation of gene expression related to citric acid cycle and oxidative phosphorylation, and a downregulation of gene expression related to complement system and inflammation. We hypothesize that the beneficial effects of MC-SFAs on prevention of fat accumulation are mediated via increased gene expression related to energy metabolism in the adipose tissue. Decreases in inflammation-related gene expression may have beneficial effects in relation to cardiometabolic diseases.


Systemic therapies in advanced hepatocellular carcinoma: How do older patients fare?
Advanced hepatocellular cancer (HCC) is the fourth leading cause of cancer-related death globally and is most common in elderly patients with a peak incidence in the UK at ages 85-89 years. In addition to the well-established risk factors of alcohol and viral hepatitis B and C, rising obesity and associated non-alcoholic fatty liver disease is projected to contribute to increased incidence of advanced HCC in elderly patients. The management of advanced HCC is changing rapidly; for over a decade the multi-kinase inhibitor sorafenib has been the only treatment option that offered a proven survival advantage, but in the last 4 years other treatment options have emerged including other kinase inhibitors, and monoclonal antibodies targeting angiogenesis and immune checkpoint inhibitors. Recent clinical trials have recruited older patients with no maximum age exclusion criteria, and age has not been found to be predictive for treatment effect in subgroup analyses. Chronological age is an unreliable measure of fitness for treatment and frailty may be a more apt descriptor, but the lack of a unified assessment tool has limited its use in current practice. Development of unified frailty assessments and prospective large-scale studies of novel systemic therapies where age and frailty are evaluated would be informative.


Hypoglycemic efficacy of chitosan-coated insulin liposomes after oral administration in mice.
To evaluate the hypoglycemic efficacy of insulin liposomes coated by chitosan with different molecular weights and concentrations after oral administration in mice. Insulin-liposomes were prepared by reversed-phase evaporation. Chitosan coating was carried out by incubation of the liposomal suspensions with the chitosan solution. The hypoglycemic efficacies of chitosan-coated insulin liposomes were investigated by monitoring the blood glucose level using the glucose oxidase method after oral administration to healthy mice. In all the insulin liposomes, the insulin liposomes coated by 0.2% chitosan (Mr 1000 kDa) showed a better hypoglycemic efficacy as compared with the other liposomes coated by chitosan. The minimum blood glucose level was 15.1%+/-6.0 % of the initial (n=6). The hypoglycemic efficacy lasted for 4 h after oral administration to mice. Chitosan-coated liposomes could reduce tryptic digestion on insulin, and enhance enteral absorption of insulin. The molecular weights and concentrations of chitosan had significant effects on hypoglycemic efficacy of chitosan-coated insulin liposomes after oral administration to healthy mice.


Threshold-related enhancement of the high-energy plateau in above-threshold detachment.
We present nonperturbative theoretical results showing a resonant-like enhancement of above-threshold detachment spectra in the region of the high-energy plateau as the laser intensity sweeps across channel thresholds. This enhancement has a pure quantum origin stemming from well-known threshold phenomena in multichannel problems whose features are clearly demonstrated in our numerical results. Similar well-known anomalies at neutral atom thresholds are expected to explain experimentally observed resonant-like enhancements of above-threshold ionization spectra.


Advanced Generation Therapeutics: Biomimetic Nanodelivery System for Tumor Immunotherapy.
Tumor immunotherapy is a safe and effective strategy for precision medicine. However, immunotherapy for most cancer cases still ends in failure, with the root causes of the immunosuppressive and extraordinary heterogeneity of the solid tumors microenvironment. The emerging biomimetic nanodelivery system provides a promising tactic to improve the immunotherapy effect while reducing the adverse reactions on nontarget cells. Herein, we summarize the relationship between tumor occurrence and tumor immune microenvironment, mechanism of tumor immune escape, immunotherapy classification (including adoptive cellular therapy, cytokines, cancer vaccines, and immune checkpoint inhibitors) and recommend target cells for immunotherapy first, and then emphatically introduce the recent advances and applications of the latest biomimetic nanodelivery systems (e.g., immune cells, erythrocytes, tumor cells, platelets, bacteria) in tumor immunotherapy. Meanwhile, we separately summarize the application of tumor vaccines. Finally, the predictable challenges and perspectives in a forward exploration of biomimetic nanodelivery systems for tumor immunotherapy are also discussed.


Screening and Characterization of Multidrug-Resistant Gram-Negative Bacteria from a Remote African Area, São Tomé and Príncipe.
The occurrence of resistance to last-resort antibiotics was evaluated among Enterobacteriaceae isolates recovered from hospitalized children in a remote African archipelago, São Tomé and Príncipe, where there is limited access to those antibiotics. Fifty patients were screened for colonization by carbapenem-, pan-aminoglycoside-, or polymyxin-resistant Enterobacteriaceae A total of 36 isolates (including 30 Escherichia coli and 4 Klebsiella pneumoniae) were recovered from 23 patients, including 26 isolates harboring the blaOXA-181 carbapenemase gene, a single isolate harboring the 16S rRNA methylase gene rmtB encoding pan-resistance to aminoglycosides, and 8 isolates coharboring both genes. A single isolate possessed the plasmid-borne colistin resistance gene mcr-1 A high clonal relationship was found for OXA-181-producing E. coli (4 clones), and conversely, three of the four OXA-181-producing K. pneumoniae isolates were clonally unrelated. This study overall showed a high prevalence of resistance to last-resort antibiotics in this country, where no epidemiological data were previously available.


Intrinsic Connectivity Provides the Baseline Framework for Variability in Motor Performance: A Multivariate Fusion Analysis of Low- and High-Frequency Resting-State Oscillations and Antisaccade Performance.
Intrinsic brain activity provides the functional framework for the brain's full repertoire of behavioral responses; that is, a common mechanism underlies intrinsic and extrinsic neural activity, with extrinsic activity building upon the underlying baseline intrinsic activity. The generation of a motor movement in response to sensory stimulation is one of the most fundamental functions of the central nervous system. Since saccadic eye movements are among our most stereotyped motor responses, we hypothesized that individual variability in the ability to inhibit a prepotent saccade and make a voluntary antisaccade would be related to individual variability in intrinsic connectivity. Twenty-three individuals completed the antisaccade task and resting-state functional magnetic resonance imaging (fMRI). A multivariate analysis of covariance identified relationships between fMRI oscillations (0.01-0.2 Hz) of resting-state networks determined using high-dimensional independent component analysis and antisaccade performance (latency, error rate). Significant multivariate relationships between antisaccade latency and directional error rate were obtained in independent components across the entire brain. Some of the relationships were obtained in components that overlapped substantially with the task; however, many were obtained in components that showed little overlap with the task. The current results demonstrate that even in the absence of a task, spectral power in regions showing little overlap with task activity predicts an individual's performance on a saccade task.


Repair of chronic tympanic membrane perforations with fibroblast growth factor.
A number of angiogenic growth factors have been shown to accelerate wound healing. Previous work has demonstrated that topical application of epidermal growth factor is effective in healing chronic tympanic membrane perforations in an animal model. Theoretically, fibroblast growth factor may result in a superior healed membrane through preferential stimulation of the fibroblasts within the middle layer of the tympanic membrane. To test this hypothesis, the effects of exogenously applied fibroblast growth factor on the chronically perforated tympanic membrane were evaluated. A buffered solution of fibroblast growth factor (25 microliters of fibroblast growth factor, 0.2 mg/ml) was administered to a Gelfoam pledget placed over chronic tympanic membrane perforations in chinchillas. Control ears were treated with Gelfoam and the buffer solution only. Complete closure of the tympanic membrane perforation was observed in 81% (13 of 16) of the fibroblast growth factor-treated ears, but in only 41% (7 of 17) of the controls (p = 0.05). Heading took place gradually, requiring an average of 4 weeks for the fibroblast growth factor-treated and 6.5 weeks for the control ears that healed. The relatively high healing rate for the control group does not imply that the pretreatment perforations were not chronic, rather there appears to be some efficacy to the control protocol of repeated applications of Gelfoam and buffer. A histologic analysis of the fibroblast growth factor-healed eardrums immediately after closure demonstrated hypertrophy of the squamous and fibrous layers of the tympanic membrane. Over time, the eardrum thinned to reach proportions similar to those of the normal tympanic membrane, including the presence of a substantial middle fibrous layer. A screening ototoxicity study revealed no structural damage to the organ of Corti after growth factor treatment. To assess the potential for systemic toxicity, blood and peripheral tissues were analyzed for radioactivity at time points during a 48-hour period after application of 25 microliters of 125I-fibroblast growth factor to the perforated tympanic membrane. More than 78% of the radioactivity remained at the application site. Given the tiny original dosage, the small fraction absorbed systemically is minuscule and highly unlikely to induce adverse effects in light of published toxicity data. On the basis of these promising safety and efficacy data in the chinchilla model, clinical trials of fibroblast growth factor in repair of chronic tympanic membrane perforations in human beings are being initiated.


Phylogenomic resolution of the class Ophiuroidea unlocks a global microfossil record.
Our understanding of the origin, evolution, and biogeography of seafloor fauna is limited because we have insufficient spatial and temporal data to resolve underlying processes. The abundance and wide distribution of modern and disarticulated fossil Ophiuroidea, including brittle stars and basket stars, make them an ideal model system for global marine biogeography if we have the phylogenetic framework necessary to link extant and fossil morphology in an evolutionary context. Here we construct a phylogeny from a highly complete 425-gene, 61-taxa transcriptome-based data set covering 15 of the 18 ophiuroid families and representatives of all extant echinoderm classes. We calibrate our phylogeny with a series of novel fossil discoveries from the early Mesozoic. We confirm the traditional paleontological view that ophiuroids are sister to the asteroids and date the crown group Ophiuroidea to the mid-Permian (270 ± 30 mega-annum). We refute all historical classification schemes of the Ophiuroidea based on gross structural characters but find strong congruence with schemes based on lateral arm plate microstructure and the temporal appearance of various plate morphologies in the fossil record. The verification that these microfossils contain phylogenetically informative characters unlocks their potential to advance our understanding of marine biogeographical processes.


Preparation and characterization of graphene oxide encapsulated gold nanoparticles.
We present a simple approach for the fabrication of graphene oxide-encapsulated gold nanoparticles using graphene oxide sheet-wrapping via electrostatic self-assembly. By mixing bovine serum albumin molecule-functionalized gold nanoparticles with graphene oxide dispersion, positively charged bovine serum albumin/gold nanoparticles easily assembled with negatively charged graphene oxide sheets through electrostatic interaction. Transmittance electron microscopy, scanning electron microscopy, atomic force microscopy, and Raman spectroscopy were used to confirm the encapsulation of graphene oxide on gold nanoparticles. Interestingly, graphene oxide sheets wrapping mainly occurs along the main body of single or a few gold nanoparticles. Additionally, by measuring the ultraviolet-visible spectroscopy spectrum, we found that the surface plasmon resonances band of the graphene oxide-encapsulated gold nanoparticles was found to become red-shifted compared to that of pristine gold nanoparticles, whereas similar to that of bovine serum albumin-coated gold nanoparticles. These results indicating that most of graphene oxide-encapsulated gold nanoparticles have good monodispersity and spherical shape. These resulting materials may potentially serve as a platform for plasmon resonance electron transfer spectroscopy or a probe for low level biosensing.


Crisis of confidence averted: Impairment of exercise economy and performance in elite race walkers by ketogenic low carbohydrate, high fat (LCHF) diet is reproducible.
We repeated our study of intensified training on a ketogenic low-carbohydrate (CHO), high-fat diet (LCHF) in world-class endurance athletes, with further investigation of a "carryover" effect on performance after restoring CHO availability in comparison to high or periodised CHO diets. After Baseline testing (10,000 m IAAF-sanctioned race, aerobic capacity and submaximal walking economy) elite male and female race walkers undertook 25 d supervised training and repeat testing (Adapt) on energy-matched diets: High CHO availability (8.6 g∙kg-1∙d-1 CHO, 2.1 g∙kg-1∙d-1 protein; 1.2 g∙kg-1∙d-1 fat) including CHO before/during/after workouts (HCHO, n = 8): similar macronutrient intake periodised within/between days to manipulate low and high CHO availability at various workouts (PCHO, n = 8); and LCHF (<50 g∙d-1 CHO; 78% energy as fat; 2.1 g∙kg-1∙d-1 protein; n = 10). After Adapt, all athletes resumed HCHO for 2.5 wk before a cohort (n = 19) completed a 20 km race. All groups increased VO2peak (ml∙kg-1∙min-1) at Adapt (p = 0.02, 95%CI: [0.35-2.74]). LCHF markedly increased whole-body fat oxidation (from 0.6 g∙min-1 to 1.3 g∙min-1), but also the oxygen cost of walking at race-relevant velocities. Differences in 10,000 m performance were clear and meaningful: HCHO improved by 4.8% or 134 s (95% CI: [207 to 62 s]; p < 0.001), with a trend for a faster time (2.2%, 61 s [-18 to +144 s]; p = 0.09) in PCHO. LCHF were slower by 2.3%, -86 s ([-18 to -144 s]; p < 0.001), with no evidence of superior "rebound" performance over 20 km after 2.5 wk of HCHO restoration and taper. Our previous findings of impaired exercise economy and performance of sustained high-intensity race walking following keto-adaptation in elite competitors were repeated. Furthermore, there was no detectable benefit from undertaking an LCHF intervention as a periodised strategy before a 2.5-wk race preparation/taper with high CHO availability. Australia New Zealand Clinical Trial Registry: ACTRN12619000794101.


Effect of sensory neuropeptides on mucus secretion from cultured goblet cells.
Airway goblet cell secretion is under the control of capsaicin-sensitive sensory nerves. Administration of capsaicin or antidromic stimulation of nerves can stimulate goblet cell secretion and also induce plasma exudation and smooth muscle contraction via a release of neuropeptides from sensory nerve endings in the airway. This study was designed to explore whether the effect of capsaicin or neuropeptides on goblet cell secretion is direct or secondary to other airway responses. We examined the effects of sensory neuropeptides including substance P (SP), neurokinin A (NKA) and neurokinin B (NKB), as well as capsaicin on cultured guinea pig tracheal goblet cells by measuring the rate of mucus discharge visually under a microscope and the release of 35SO4 radiolabeled mucin-like glycoconjugates. Goblet cells in culture spontaneously secreted intracellular granules at a mean rate of about 3 times/min. SP and NKA increased secretion in a dose-dependent manner. SP was more potent than NKA with maximum responses of 52% and 37% at 10(-8) M, respectively. Quantitative measurements of 35SO4 radiolabeled mucin-like glycoprotein (MLGP) secreted by goblet cells also revealed an increase (109.2%) in mucin secretion caused by SP (10(-8) M) compared with the vehicle control. Neither capsaicin nor NKB caused any significant change in the goblet cell secretory rate. The effects of SP on the secretory rate or release of radiolabeled mucin were not potentiated by an enkephalinase inhibitor, thiorphan (10(-5) M). Sensory neuropeptides SP and NKA directly stimulate goblet cell secretion, probably through the tachykinin receptor of the NK-1 subtype as suggested by a greater potency of SP. There was no direct effect of capsaicin on goblet cell secretion.


On the sharpness of the interfaces in metallic multilayers.
We show that the three most relevant magnetic properties (magnetic moment, critical temperature, and interlayer exchange coupling) of metallic multilayers can be reproduced with good accuracy by first principles theory, provided that the picture of atomically sharp interfaces is abandoned and one allows instead for both interface alloying and interface roughness. The interface of a metallic multilayer (exemplified by the Fe/V system) is demonstrated to, at best, have interdiffusion essentially over two to three atomic layers on each side of the interface. Our conclusions are the result of combining experimental work with theoretical modeling, and we argue that this approach is the best avenue to obtain accurate information about the interface quality of metallic multilayers.


Medicinal plants used in the management of cancers by residents in the Elgon Sub-Region, Uganda.
In Uganda, medicinal plants have been utilized to treat a variety of ailments, including cancer. However, there is little information available about the medicinal plants used to treat cancer in the Elgon subregion. As a result, the current study documented the plant species used in the management of cancer in the Elgon sub-region. Data were gathered by observation, self-administered questionnaires, interview guides, and guided field trips. Analyzing descriptive statistics and creating graphs were done using SPSS (version 21.0) and GraphPad Prism® version 9.0.0, respectively. Well-established formulae were used to calculate quantitative indices. The narratives were interpreted using major theories and hypotheses in ethnobotany. A total of 50 plant species from 36 families were documented, and herbal knowledge was mainly acquired through inheritance. Fabaceae and Asteraceae comprised more plant species used in herbal preparation. Most plants were collected from forest reserves (63%); herbal therapies were made from herbs (45%); and leaves were primarily decocted (43%). The most frequently used plants were Tylosema fassoglensis, Hydnora abyssinica, Azidarachata indica, Prunus Africana, Kigelia africana, Syzygium cumini, Hydnora africana, Rhoicissus tridentata, Albizia coriaria, and Plectranthus cuanneus. All the most commonly used plants exhibited a high preference ranking (60-86%) and reliability level (74.1-93.9%). Generally, the ICF for all the cancers treated by medicinal plants was close to 1 (0.84-0.95). The ten most commonly utilized plants were favored, dependable, and most important for treating all known cancers. As a result, more investigation is required to determine their phytochemistry, toxicity, and effectiveness in both in vivo and in vitro studies. This could be a cornerstone for the pharmaceutical sector to develop new anticancer medications.


Urocortin 3 modulates social discrimination abilities via corticotropin-releasing hormone receptor type 2.
Urocortin 3 (UCN3) is strongly expressed in specific nuclei of the rodent brain, at sites distinct from those expressing urocortin 1 and urocortin 2, the other endogenous ligands of corticotropin-releasing hormone receptor type 2 (CRH-R2). To determine the physiological role of UCN3, we generated UCN3-deficient mice, in which the UCN3 open reading frame was replaced by a tau-lacZ reporter gene. By means of this reporter gene, the nucleus parabrachialis and the premammillary nucleus were identified as previously unknown sites of UCN3 expression. Additionally, the introduced reporter gene enabled the visualization of axonal projections of UCN3-expressing neurons from the superior paraolivary nucleus to the inferior colliculus and from the posterodorsal part of the medial amygdala to the principal nucleus of the bed nucleus of the stria terminalis, respectively. The examination of tau-lacZ reporter gene activity throughout the brain underscored a predominant expression of UCN3 in nuclei functionally connected to the accessory olfactory system. Male and female mice were comprehensively phenotyped but none of the applied tests provided indications for a role of UCN3 in the context of hypothalamic-pituitary-adrenocortical axis regulation, anxiety- or depression-related behavior. However, inspired by the prevalent expression throughout the accessory olfactory system, we identified alterations in social discrimination abilities of male and female UCN3 knock-out mice that were also present in male CRH-R2 knock-out mice. In conclusion, our results suggest a novel role for UCN3 and CRH-R2 related to the processing of social cues and to the establishment of social memories.


Modulation of nuclear statin expression in rat thyroid follicle cell following administration of thyroid stimulating hormone.
This study was designed to examine the state of proliferation in the rat thyrocyte following the administration of thyroid stimulating hormone (TSH). An immunohistochemical technique involving the use of a monoclonal antibody to statin, a nonproliferation-specific nuclear antigen, was developed to measure the subpopulation of cells that have ceased to divide. Following the random assignment of young male Sprague-Dawley rats into various groups, the rats in the control group received a single intraperitoneal (i-p) injection of normal saline, whereas the experimental groups received single i-p injections of TSH at doses of 0.25, 0.50, and 1.0 IU, respectively. All rats were subsequently sacrificed in groups of three at 1, 2, 4, and 24 hours. The statin antibody label was readily identified within the follicle cell nucleus. Results revealed a statistically significant transient decrease in the mean percent statin-positive nuclei in the TSH-treated groups. The time- and dose-dependent effect of TSH was maximal at 2 hours and no longer discernible at 24 hours. A second experiment involving the chronic administration of TSH (i-p 0.25 IU twice daily) resulted in a cumulative response with a statistically significant progressive decrease in the mean percent of statin-positive nuclei at 5 and 10 days, returning to near normal values 5 days following the cessation of treatment. Determination of the nuclear optical density of the statin reaction product by image analysis techniques revealed that a single injection of TSH resulted in a rapid disappearance of the statin nuclear protein. This result suggests that the disappearance of statin in the nucleus appears to reflect the event of cells leaving the nondividing quiescent state to resume the cell cycle traverse following the administration of TSH. The disappearance of statin appears as an early nuclear event that parallels the earliest known cytoplasmic pinocytotic response to TSH in the rat thyroid follicle cell.


Emerging Biofabrication Strategies for Engineering Complex Tissue Constructs.
The demand for organ transplantation and repair, coupled with a shortage of available donors, poses an urgent clinical need for the development of innovative treatment strategies for long-term repair and regeneration of injured or diseased tissues and organs. Bioengineering organs, by growing patient-derived cells in biomaterial scaffolds in the presence of pertinent physicochemical signals, provides a promising solution to meet this demand. However, recapitulating the structural and cytoarchitectural complexities of native tissues in vitro remains a significant challenge to be addressed. Through tremendous efforts over the past decade, several innovative biofabrication strategies have been developed to overcome these challenges. This review highlights recent work on emerging three-dimensional bioprinting and textile techniques, compares the advantages and shortcomings of these approaches, outlines the use of common biomaterials and advanced hybrid scaffolds, and describes several design considerations including the structural, physical, biological, and economical parameters that are crucial for the fabrication of functional, complex, engineered tissues. Finally, the applications of these biofabrication strategies in neural, skin, connective, and muscle tissue engineering are explored.


Development of an improved Streptococcus uberis experimental mastitis challenge model using different doses and strains in lactating dairy cows.
Developing a reliable mastitis challenge infection model is required to test new intramammary antimicrobial preparations, other novel bovine mastitis treatments, and study mastitis pathogenesis. Three treatment groups of Holstein Friesian cows in active lactation were administered two doses (10(4) and 10(6) cfu/quarter) on a single occasion with one of the three Streptococcus uberis strains (BFR6019, MFF1283 and SA002) suspended in 5 ml of sterile PBS, administered via intramammary inoculation immediately after milking. All quarters that were challenged with S. uberis strains MLF1283 and BFR6019 showed clinical signs of mastitis on day 1 and 2 after the challenge. Strain SA002 had a lower rate of inducing clinical mastitis which was detected later than day 3 after the challenge. We successfully developed a rapid and reliable model for inducing experimental S. uberis mastitis with 100% success rate in cows in active lactation. On the basis of the correlation results between strains, RAPD fingerprinting results, clinical findings, and a 100% success rate of mastitis induction for low and high doses S. uberis strains MLF1283 and BFR6019, strain virulence seems to be a more important effect than challenge dose in induction of clinical mastitis following experimental challenge.


Model-based control of observer bias for the analysis of presence-only data in ecology.
Presence-only data, where information is available concerning species presence but not species absence, are subject to bias due to observers being more likely to visit and record sightings at some locations than others (hereafter "observer bias"). In this paper, we describe and evaluate a model-based approach to accounting for observer bias directly--by modelling presence locations as a function of known observer bias variables (such as accessibility variables) in addition to environmental variables, then conditioning on a common level of bias to make predictions of species occurrence free of such observer bias. We implement this idea using point process models with a LASSO penalty, a new presence-only method related to maximum entropy modelling, that implicitly addresses the "pseudo-absence problem" of where to locate pseudo-absences (and how many). The proposed method of bias-correction is evaluated using systematically collected presence/absence data for 62 plant species endemic to the Blue Mountains near Sydney, Australia. It is shown that modelling and controlling for observer bias significantly improves the accuracy of predictions made using presence-only data, and usually improves predictions as compared to pseudo-absence or "inventory" methods of bias correction based on absences from non-target species. Future research will consider the potential for improving the proposed bias-correction approach by estimating the observer bias simultaneously across multiple species.


DeepBAR: A Fast and Exact Method for Binding Free Energy Computation.
The fast and accurate calculation of standard binding free energy has many important applications. Existing methodologies struggle at balancing accuracy and efficiency. We introduce a new method to compute binding free energy using deep generative models and the Bennett acceptance ratio method (DeepBAR). Compared to the rigorous potential of mean force (PMF) approach that requires sampling from intermediate states, DeepBAR is an order-of-magnitude more efficient as demonstrated in a series of host-guest systems. Notably, DeepBAR is exact and does not suffer from approximations for entropic contributions used in methods such as the molecular mechanics energy combined with the generalized Born and surface area continuum solvation (MM/GBSA). We anticipate DeepBAR to be a valuable tool for computing standard binding free energy used in drug design.


Reduction in Serum LDL Cholesterol Using a Nutrient Compendium in Hyperlipidemic Adults Unable or Unwilling to Use Statin Therapy: A Double-Blind Randomized Crossover Clinical Trial.
Many hyperlipidemic patients prescribed β-hydroxy-β-methylglutaryl coenzyme A reductase inhibitors (statins) are unable or unwilling to take them. A hedonically acceptable snack-based solution formulated from cholesterol-lowering food ingredients could represent a therapeutic alternative but has not been tested in this population. To evaluate the effect of snacks containing a compendium of functional bioactives on fasting LDL cholesterol in statin candidates unwilling to use or intolerant to ≥1 statin drug. Secondary outcomes included changes in circulating total cholesterol (TC), triglycerides, HDL cholesterol, fasting glucose, insulin, and high-sensitivity C-reactive protein concentrations, as well as effects of single-nucleotide polymorphisms (SNPs) on outcome. This multicenter, randomized, double-blind, free-living crossover study was composed of 2 regimented phases of 4 wk each, separated by a 4-wk washout. Eighteen men and 36 women, with a mean ± SD age of 49 ± 12 y and mean ± SD LDL cholesterol of 131 ± 32.1 mg/dL, were instructed to ingest a variety of ready-to-eat snacks twice daily as a substitute for something they were consuming already. Other behavior changes were actively discouraged. Treatment products provided ≥5 g fiber, 1000 mg ω-3 (n-3) fatty acids, 1000 mg phytosterols, and 1800 μmol antioxidants per serving. Control products were calorie-matched like-items drawn from the general grocery marketplace. Serum lipids were measured at baseline and the end of each phase and compared using the ANOVA model. Compliance to study foods was confirmed by serum 18:3n-3 concentration assessment. Comparing intervention phase endpoints, LDL cholesterol was reduced a mean ± SD of 8.80 ± 1.69% (P < 0.0001), and TC was reduced a mean ± SD of 5.08 ± 1.12% (P < 0.0001) by treatment foods compared with control foods, whereas effects on other analytes did not differ between treatments. SNPs were not significantly related to outcomes (P ≥ 0.230). Compliance with study foods was 95%. Consumption of hedonically acceptable snacks containing a compendium of cholesterol-lowering bioactive compounds can rapidly and meaningfully reduce LDL cholesterol in adult patients unable or unwilling to take statin drugs. This trial was registered at clinicaltrials.gov as NCT02341924.


FeMo Heterobimetallic Dithiolate Complexes: Investigation of Their Electron Transfer Chemistry and Reactivity toward Acids, a Density Functional Theory Rationalization.
The electrochemical behavior of complexes [FeMo(CO)5(κ2-dppe)(μ-pdt)] (1) and [FeMo(CO)4(MeCN)(κ2-dppe)(μ-pdt)] (2), in the absence and in the presence of acid, has been investigated. The reduction of 1 follows at slow scan rates, in CH2Cl2-[NBu4][PF6] and acid-free media, an ECrevE mechanism that is supported by cyclic voltammetry (CV) experiments and digital CV simulations. In MeCN-[NBu4][PF6], the electrochemical reduction of 1 is the same as in dichloromethane and follows an ECE mechanism at slow scan rates, but with a positive shift of the redox potentials. In contrast, the oxidation of 1 is strongly solvent-dependent. In dichloromethane, the oxidation of 1 is reversible and involves a single electron, while in acetonitrile, it is irreversible at moderate and slow scan rates ( v ≤ ca. 1 V s-1), and some chemical reversibility is apparent at higher scan rates ( v = 10 V s-1). Density functional theory calculations revealed that the chemical step in the ECrevE mechanism corresponds to the dissociation of one PPh2 end of the diphosphine ligand and the transfer of the semibridging CO to the Fe atom, similarly to the mechanism observed in the FeFe analogue complex. However, in the case of 1, the subsequent coordination of the phosphine ligand to the other metal is an unfavorable process.


Teenagers' motorcycle gang community aggression from the Personal Fable and risk-taking behavior perspective.
The number of criminal acts committed by teenagers who are members of the motorcycle gang community in the Makassar City of Indonesia continues to increase at an alarming rate. Among the antisocial behaviors of teenagers in motorcycle gangs which might lead to criminal behavior is aggression. This study aimed to examine the aggression of teenagers in the motorcycle gang community in one area of Makassar City from the Personal Fable (dimensions of omnipotence, uniqueness and invulnerability) and risk-taking behavior perspective. Data were obtained through survey research involving 110 participants. Data collection tools included Personal Fable questionnaires, risk-taking behavior questionnaires, and aggression questionnaires. Multiple linear regression analysis resulted in a R square value of 0.516 (p=0.00). The results show that the Personal Fable, especially the dimensions of invulnerability, and risk-taking behavior had remarkable contributions in the adolescent aggression score, while the omnipotence and uniqueness dimensions of the Personal Fable were not found as significant predictors. The results implied that perceived invulnerability and tendency to engage in risky behavior could markedly predict juvenile aggression. Social intervention aimed at adolescents' talent and potential development is necessary to channel the destructive tendency of motorcycle gang members into a more favorable hobby.


The evolutionary diversification of cyanobacteria: molecular-phylogenetic and paleontological perspectives.
Cyanobacteria have played a significant role in Earth history as primary producers and the ultimate source of atmospheric oxygen. To date, however, how and when the group diversified has remained unclear. Here, we combine molecular phylogenetic and paleontological studies to elucidate the pattern and timing of early cyanobacterial diversification. 16S rRNA, rbcL, and hetR genes were sequenced from 20 cyanobacterial strains distributed among 16 genera, with particular care taken to represent the known diversity of filamentous taxa. Unlike most other bacteria, some filamentous cyanobacteria evolved a degree of cell differentiation, producing both specialized cells for nitrogen fixation (heterocysts) and resting cells able to endure environmental stress (akinetes). Phylogenetic analyses support the hypothesis that cyanobacteria capable of cell differentiation are monophyletic, and the geological record provides both upper and lower bounds on the origin of this clade. Fossil akinetes have been identified in 1,650- to 1,400-mega-annum (Ma) cherts from Siberia, China, and Australia, and what may be the earliest known akinetes are preserved in approximately 2,100-Ma chert from West Africa. Geochemical evidence suggests that oxygen first reached levels that would compromise nitrogen fixation (and hence select for heterocyst differentiation) 2,450-2,320 Ma. Integrating phylogenetic analyses and geological data, we suggest that the clade of cyanobacteria marked by cell differentiation diverged once between 2,450 and 2,100 Ma, providing an internal bacterial calibration point for studies of molecular evolution in early organisms.


Blueprint for Restructuring a Department of Surgery in Concert With the Health Care System During a Pandemic: The University of Wisconsin Experience.
The current health care environment is complex. Systems often cross US state boundaries to provide care to patients with a wide variety of medical needs. The coronavirus disease 2019 pandemic is challenging health care systems across the globe. Systems face varying levels of complexity as they adapt to the new reality. This pandemic continues to escalate in hot spots nationally and internationally, and the worst strain on health care systems may be yet to come. The purpose of this article is to provide a road map developed from lessons learned from the experience in the Department of Surgery at the University of Wisconsin School of Medicine and Public Health and University of Wisconsin Health, based on past experience with incident command structures in military combat operations and Federal Emergency Management Agency responses. We will discuss administrative restructuring leveraging a team-of-teams approach, provide a framework for deploying the workforce needed to deliver all necessary urgent health care and critical care to patients in the system, and consider implications for the future.


Somatic maturation and the relationship between bone mineral variables and types of sports among adolescents: cross-sectional study.
Peak height velocity (PHV) is an important maturational event during adolescence that affects skeleton size. The objective here was to compare bone variables in adolescents who practiced different types of sports, and to identify whether differences in bone variables attributed to sports practice were dependent on somatic maturation status. Cross-sectional study, São Paulo State University (UNESP). The study was composed of 93 adolescents (12 to 16.5 years old), divided into three groups: no-sport group (n = 42), soccer/basketball group (n = 26) and swimming group (n = 25). Bone mineral density and content were measured using dual-energy x-ray absorptiometry and somatic maturation was estimated through using peak height velocity. Data on training load were provided by the coaches. Adolescents whose PHV occurred at an older age presented higher bone mineral density in their upper limbs (P = 0.018). After adjustments for confounders, such as somatic maturation, the swimmers presented lower values for bone mineral density in their lower limbs, spine and whole body. Only the bone mineral density in the upper limbs was similar between the groups. There was a negative relationship between whole-body bone mineral content and the weekly training hours (β: -1563.967; 95% confidence interval, CI: -2916.484 to -211.450). The differences in bone variables attributed to sport practice occurred independently of maturation, while high training load in situations of hypogravity seemed to be related to lower bone mass in swimmers.


[Pharmacodynamics of inhalation broncholytic agents introduced in a single dose by nebulizer in patients with severe exacerbation of bronchial asthma].
To study pharmacodynamics and safety of inhalatory beta-2-adrenostimulators and M-cholinolytics given via nebulizer in patients with severe exacerbation of bronchial asthma (BA). The study covered 78 patients with severe exacerbation of BA (mean age--48.6 +/- 15.0 years). The patients were randomized into 4 groups: 23, 20, 18 and 17 patients, respectively. They were treated with: ventolin nebuly (2.5 mg), berodual (0.25 mg ipratropium bromide and 0.5 mg phenoterol), atrovent (0.5 mg), berotek (1.0 mg by nebulizer Pulmo-Aide 56501). Efficiency and safety of the treatment was assessed by the data of external respiration function, arterial blood gases and ECG each 30 min for 3 hours. In patients with severe exacerbation of BA pharmacodynamics of all the studied drugs was characterized by less duration and potency of the action. Salbutamol and berotek were effective for 180 min, atrovent--for 30-60 min. Inhalation broncholytics had no such serious side effects as prolongation of corrected interval Q-T or onset of arrhythmia. Berotek demonstrated longer action on heart rate than salbutamol. Severe complication of BA is treated more effectively with combination of beta 2-adrenomimetic with atrovent.


Prodromal Markers of Parkinson's Disease in Patients With Essential Tremor.
Background: Essential tremor (ET) is manifested as an isolated syndrome of bilateral upper limb action tremor. Parkinson's disease (PD) is the second most common neurodegenerative disease, with typical motor symptoms of bradykinesia, rigidity, and resting tremor. ET-PD describes the new-onset of PD in ET patients. Recently, numerous studies on epidemiology, genetics, pathology, clinical features, and neuroimaging studies are challenging the idea that ET is an isolated disease, suggesting that patients with ET have the tendency to develop PD. Methods: In this review article, we collected recent findings that reveal prodromal markers of PD in patients with ET. Results: Substantia nigra hyperechogenicity serves as a prodromal marker for predicting the development of PD in patients with ET and provides a reference for therapeutic strategies. Additional potential markers include other neuroimaging, clinical features, heart rate, and genetics, whereas others lack sufficient evidence. Conclusion: In consideration of the limited research of PD in patients with ET, we are still far from revealing the prodromal markers. However, from the existing follow-up studies on ET patients, Substantia nigra hyperechogenicity may enable further exploration of the relationship between ET and PD and the search for pathogenesis-based therapies.


[Progress in Research and Application of CAR-T Cell Therapy in T-Lymphocyte Tumors --Review].
T-lymphocyte tumors are a group of diseases containing various types of lymphatic system tumors, with strong heterogeneity and poor clinical outcomes. Chimeric antigen receptor T (CAR-T) cell therapy, as a new immune cell therapy, has made a breakthrough in the field of B-lymphocyte tumors. People are interested in the application prospect of this technique in the field of T-lymphocyte tumors. Some studies have shown that CAR-T cell therapy has made some progress in the treatment of T-lymphocyte tumors, and CAR-T for some targets has entered the stage of clinical trials. However, due to the characteristics of T cells, there are also many challenges. This article reviews the research and application of CAR-T cell therapy in T-lymphocyte tumors.


Partial hexokinase II knockout results in acute ischemia-reperfusion damage in skeletal muscle of male, but not female, mice.
Cellular studies have demonstrated a protective role of mitochondrial hexokinase against oxidative insults. It is unknown whether HK protective effects translate to the in vivo condition. In the present study, we hypothesize that HK affects acute ischemia-reperfusion injury in skeletal muscle of the intact animal. Male and female heterozygote knockout HKII (HK(+/-)), heterozygote overexpressed HKII (HK(tg)), and their wild-type (WT) C57Bl/6 littermates mice were examined. In anesthetized animals, the left gastrocnemius medialis (GM) muscle was connected to a force transducer and continuously stimulated (1-Hz twitches) during 60 min ischemia and 90 min reperfusion. Cell survival (%LDH) was defined by the amount of cytosolic lactate dehydrogenase (LDH) activity still present in the reperfused GM relative to the contralateral (non-ischemic) GM. Mitochondrial HK activity was 72.6 +/- 7.5, 15.7 +/- 1.7, and 8.8 +/- 0.9 mU/mg protein in male mice, and 72.7 +/- 3.7, 11.2 +/- 1.4, and 5.9 +/- 1.1 mU/mg in female mice for HK(tg), WT, and HK(+/-), respectively. Tetanic force recovery amounted to 33 +/- 7% for male and 17 +/- 4% for female mice and was similar for HK(tg), WT, and HK(+/-). However, cell survival was decreased (p = 0.014) in male HK(+/-) (82 +/- 4%LDH) as compared with WT (98 +/- 5%LDH) and HK(tg) (97 +/- 4%LDH). No effects of HKII on cell survival was observed in female mice (92 +/- 2% LDH). In conclusion, in this mild model of acute in vivo ischemia-reperfusion injury, a partial knockout of HKII was associated with increased cell death in male mice. The data suggest for the first time that HKII mediates skeletal muscle ischemia-reperfusion injury in the intact male animal.


[Surgical treatment of patients with perforating gastroduodenal ulcers].
Under analysis were the results of treatment of 267 patients with perforating gastroduodenal ulcers for the period from 1992 till 1997. Radical operations were fulfilled in 86% of the patients. Suture of the perforation and selective proximal vagotomy were performed in 118 patients with ulcers of the duodenum having no intraoperative signs of duodenostasis, in the others resection of the stomach was used. Palliative operations (suturing the perforation) were performed in 15% of the patients. General lethality was 3.7%, postoperative--3%. Excellent and good results were obtained in 95.5% of the patients.


Time and labor costs associated with administration of intravenous bisphosphonates for breast or prostate cancer patients with metastatic bone disease: a time and motion study.
To estimate, using a time and motion method, the time and labor costs associated with the administration of zoledronic acid and pamidronate in cancer patients with metastatic bone diseases. During clinic visits for participating patients receiving intravenous zoledronic acid or pamidronate, all times and activities associated with the administration of bisphosphonates were recorded by a trained observer using a stopwatch and data recording forms. The total time associated with the administration of bisphosphonates was estimated and converted to labor costs by applying corresponding health care professional hourly wage rates plus the fringe-benefit rate. The costs were presented in 2011 Canadian dollars. A convenience sample of 37 patients from 2 hospital outpatient oncology clinics in Ontario and Quebec participated in the study. Nineteen patients were diagnosed with breast cancer and 18 with prostate cancer. The average patient age was 66 years, and patients had been diagnosed with cancer and metastatic bone disease for 8 years and 3 years, respectively. The times and costs associated with the administration of bisphosphonates for the 28 patients who did not receive concurrent chemotherapy during the scheduled clinic visits are also reported. The mean infusion time for patients receiving zoledronic acid was 20.6 minutes. With the use of ambulatory infusion devices, the mean infusion time of pamidronate was 23 minutes (limited to observations of patients who were seated during administration). In contrast, the mean infusion time using regular infusion devices was 162 minutes. The mean labor cost for administering zoledronic acid was $20. The mean labor cost for administering pamidronate was $10 using ambulatory infusion devices and $68 using regular infusion devices. The time burden to cancer patients with metastatic bone disease who receive intravenous bisphosphonates and the costs to the health care system are substantial, especially when regular infusion devices are used.


Sensory evaluations of a novel iron and zinc-enriched powder for the potential treatment and prevention of iron deficiency in women of reproductive age.
Iron deficiency (ID) and ID with anaemia (IDA) are serious global health problems that disproportionately affect women aged 15-49 years. Although food fortification is one of the most effective and sustainable ways to combat nutritional deficiencies, iron remains one of the most difficult micronutrients to fortify, given its tendency to react strongly with food constituents. Therefore, it is important to assess the sensory properties of foods fortified with iron to determine the acceptability and palatability in target populations. We aimed to determine the palatability and acceptability of a novel iron and zinc-enriched powder fortified in tap water by conducting sensory evaluations in 35 women of reproductive age using a 9-point hedonic scale, where participants rated the sensory properties of six samples containing different amounts of the active or placebo powder. We found significant differences between samples reconstituted at 1, 2, and 3 g/L for sensory properties, including overall taste. Participants were found to be more willing to drink the mineral-enriched powder when prepared at the lowest concentration (1 g/L) compared to higher concentrations. Our results provide important insight into the sensory qualities of a novel formulation of an iron and zinc-enriched powder for at-home fortification and indicate consumer acceptability in reproductive-aged women, a key group at risk for ID/IDA. If found to improve iron status, novel treatments like this product will contribute to global efforts to develop safe, acceptable and sustainable interventions for ID and IDA.


Repair of Partial Atrioventricular Septal Defect: Age and Outcomes.
We evaluated the outcomes of patients undergoing surgical repair of partial atrioventricular septal defect (AVSD) and analyzed the effect of age on outcome. In this single-center retrospective study, we included all children who underwent repair of partial AVSD between 1990 and 2014. We divided the patients into 4 age quartiles (first quartile: 0-0.75 years, n = 22; second quartile: 0.75-1.5 years, n = 21; third quartile: 1.5-3.75 years, n = 22; and fourth quartile: >3.75 years, n = 21). These quartiles were evaluated for their association with the time-to-event outcomes of survival, freedom from left atrioventricular valve regurgitation (LAVVR), and freedom from reoperation using log-rank analysis. During the study period, 86 patients underwent partial AVSD repair at a median age of 1.5 years. There were no operative deaths and 2 late deaths (unknown cause and trauma). There were 13 reoperations. The most common cause of reoperation was left ventricular outflow tract obstruction (LVOTO) (5 patients [first quartile, 2 cases; second quartile, 1 case; third quartile, 2 cases, and fourth quartile, 0 cases]). LAVV reoperation for insufficiency or stenosis was performed in 4 patients (first quartile, 1 case; second quartile, 1 case; third quartile, 1 case; and fourth quartile, 1 case). Two patients underwent pacemaker placement (second quartile, 1 case and fourth quartile, 1 case). There were no statistically significant differences in the most common complications-LVOTO, LAVVR, and AV heart block-between the 4 age quartiles. Median follow-up was 7.1 years (interquartile range [IQR], 0.8-11.4 years). On echocardiography, 72 patients (84%) had less than or equal to mild LAVVR, 8 (9%) patients had mild to moderate LAVVR, 5 (6%) patients had moderate LAVVR, and 1 (1%) patient had severe LAVVR. Age at repair had no significant association with degree of late AV valve insufficiency. Results of partial AVSD repair at a median age of 1.5 years are excellent. Operating at this age is not associated with increased mortality, reoperation, or LAVVR.


[Neurogliaform cells: neurochemistry, spatial arrangement, and their role in the neocortical inhibitory system].
The neurogliaform cells (NGFC) localized in area 4 of the human motor cortex were found to express choline acetyl transferase (ChAT), GABA, and calbindin. ChAT-positive neurons were located in cortical layer II. Their dendrites lay in a close proximity to those of pyramid cells, neighbouring neurogliaform cells, and bodies and dendrites of other cortical neurons. The NGFCs revealed by Golgi staining fell into two groups. Cells of the first group had locally (within cortical layer II) spreading axons, while those of the second group had axons extending into the adjacent layers. Neurochemical heterogeneity of NGFCs is discussed in the context of information processing in cortical modules and interaction of excitatory and inhibitory interneurons.


Parenting Needs of Urban, African American Fathers.
Fathers play a critical role in children's development; similarly, fatherhood positively affects men's health. Among the larger population of fathers relatively little is known about the parenting knowledge of urban, African American fathers. Focusing on urban, African American fathers, the objectives of this study were to (1) understand the primary sources from which fathers learn about parenting, (2) determine where and how fathers prefer to receive future parenting education, and (3) explore the information perceived as most valuable to fathers and how this compares with the recommended anticipatory guidance (Bright Futures-based) delivered during well visits. Five focus groups, with a total of 21 participants, were conducted with urban fathers at a community-based organization. Study eligibility included being more than 18 years old, English speaking, and having at least one child 0 to 5 years old. During the focus groups, fathers were asked where they received parenting information, how and where they preferred to receive parenting information, and what they thought about Bright Futures parenting guidelines. Fathers most commonly described receiving parenting information from their own relatives rather than from their child's health care provider. Most fathers preferred to learn parenting from a person rather than a technology-based source and expressed interest in learning more about parenting at community-based locations. Although fathers viewed health care providers' role as primarily teaching about physical health, they valued Bright Futures anticipatory guidance about parenting. Fathers valued learning about child rearing, health, and development. Augmenting physician counseling about Bright Futures with community-based parenting education may be beneficial for fathers.


Urinary excretion of monoacetyl polyamines in patients with non-Hodgkin's lymphoma.
The pretreatment concentrations of polyamines were determined in the 24-hr urine of 14 patients with widespread non-Hodgkin's lymphoma. In ten of 14 patients, the ratio of N1-acetylspermidine to N8-acetylspermidine was significantly higher than the mean for normal subjects. These results confirm our previous observations that the urinary excretion of N1-acetylspermidine is increased in some patients with lymphoma and suggest that the determination of urinary acetyl polyamines may be useful in conjunction with other procedures in the diagnosis of lymphoma. The ratio of N1-acetylspermidine to N8-acetylspermidine in the postchemotherapy 24-hr urine was 25 in one patient who had diffuse histiocytic lymphoma. This is the highest ratio ever reported. The patient responded well to chemotherapy, and rapid lysis of lymphoma lesion was observed. The potential utility of the rapid increase in the ratio of N1-acetylspermidine to N8-acetylspermidine as a criterion of tumor lysis is of interest and is currently under further investigation.


Monoclonal antibodies to HLA-DP, DQ, and DR determinants: functional effects on the activation and proliferation of normal and EBV-transformed B cells.
To investigate the function of HLA class II molecules in B-cell activation, we generated three new anti-HLA class II monoclonal antibodies with differing specificities for DP, DQ, and DR determinants. These were tested for their ability to inhibit various B- and T-lymphocyte responses. Each of these antibodies (NB-29, DH-84, and DH-224) immunoprecipitates a heterodimer of approximately 35,000 and 28,000 mol wt from 125I-surface-labeled B-lymphoma cells, as shown by SDS-PAGE. NB-29 (IgG1) detects a polymorphic DQ determinant, while DH-224 (IgG1) is reactive with monomorphic DR determinants, and DH-84 (IgG2a) has specificity for DP, DQ, and DR. Both DH-224 and DH-84, but not NB-29, were found to inhibit significantly the stimulation of peripheral blood mononuclear cells (PBMC) by anti-mu (70%-90% inhibition) and by lipopolysaccharide (80%-90% inhibition), as measured by incorporation of tritiated thymidine. When added to highly purified populations of peripheral blood B cells, none of these anti-class II monoclonal antibodies inhibited anti-mu-induced stimulation. This suggests that the inhibitory effect that DH-224 and DH-84 have on the stimulation of unfractionated PBMC may be due to their ability to interfere with the action of accessory cells. Epstein-Barr-virus (EBV)-transformed B-cell lines, in contrast, showed substantial inhibition of growth when cultured in the presence of any of the three antibodies. With respect to T cells, DH-84 and DH-224 strongly inhibited the mixed lymphocyte response; NB-29 did not. None of these antibodies inhibited stimulation of PBMC by phytohemagglutinin (PHA). These findings suggest that DQ and DR HLA class II molecules have differing roles in B-cell activation and document a direct antiproliferative effect of anti-HLA class II monoclonal antibodies on the growth of EBV-transformed cell lines.


Amblyopic abnormality involves neural mechanisms concerned with movement processing.
In strabismic amblyopia the detection of apparent movement for counterphase gratings is considerably more impaired than the detection of pattern. No such anomaly is found for the detection of changes from a blank field when gradual or abrupt onsets or offsets of the temporal grating presentation are used. Similarly, normal peripheral vision is relatively poor in detecting alternation of spatial phase. It is concluded that the observed movement abnormality does not reflect a loss in sensitivity of transient mechanisms but rather a visual insensitivity to spatial phase. This would explain why perceptual distortions and low optotype acuity occur in amblyopes with normal contrast sensitivity.


[Understanding women with advanced gynecological cancer: a Heideggerian approach].
This qualitative phenomenological research was carried out in order to understand how women experience living with advance gynecological cancer. We chose to make a qualitative survey in a phenomenological approach, based on the following directive question: "I'd like you to tell me your experience: 'How is it to be a woman with gynecological cancer?" ' Six women were interviewed. The ontological unification which emerged from the speeches were analyzed and interpreted according to Martin Heidegger's philosophical referential. These unifications made possible to see ways to care for these women that go far beyond technical and scientific knowledge. It is necessary to understand what has been lived by the other, thus ensuring a quality of care that contemplates subjectivity and inter-subjectivity.