The cost-effectiveness and budget impact of stepwise addition of bolus insulin in the treatment of type 2 diabetes: evaluation of the FullSTEP trial.
Abstract Background and aims: Intensification of basal insulin-only therapy in type 2 diabetes is often achieved through addition of bolus insulin 3-times daily. The FullSTEP trial demonstrated that stepwise addition (SWA) of bolus insulin aspart was non-inferior to full basal-bolus (FBB) therapy and reduced the rate of hypoglycemia. Here the cost-effectiveness and budget impact of SWA is evaluated. Cost-effectiveness and budget impact models were developed to assess the cost and quality-of-life (QoL) implications of intensification using SWA compared with FBB in the US setting. At assessment, SWA patients added one bolus dose to their current regimen if the HbA1c target was not met. SWA patients reaching three bolus doses used FBB event rates. Outcomes were evaluated at trial end and projected annually up to 5 years. Models captured hypoglycemic events, the proportion meeting HbA1c target, and self-measured blood glucose. Event rates and QoL utilities were taken from trial data and published literature. Costs were evaluated from a healthcare-payer perspective, reported in 2013 USD, and discounted (like clinical outcomes) at 3.5% annually. This analysis applies to patients with HbA1c 7.0-9.0% and body mass index <40 kg/m(2). SWA was associated with improved QoL and reduced costs compared with FBB. Improvement in QoL and cost reduction were driven by lower rates of hypoglycemia. Sensitivity analyses showed that outcomes were most influenced by the cost of bolus insulin and QoL impact of symptomatic hypoglycemia. Budget impact analysis estimated that, by moving from FBB to SWA, a health plan with 77,000 patients with type 2 diabetes, of whom 7.8% annually intensified to basal-bolus therapy, would save USD 1304 per intensifying patient over the trial period. SWA of bolus insulin should be considered a beneficial and cost-saving alternative to FBB therapy for the intensification of treatment in type 2 diabetes.


Hepatitis E virus seroprevalence and determinants in various study populations in the Netherlands.
The epidemiology of hepatitis E virus (HEV) is not fully understood. In this study, we assessed putative risk factors for HEV seropositivity in various study populations in the Netherlands. Data and samples from five different study populations were analysed: (A) blood donors (n = 5,239), (B) adults reporting a vegetarian life style since the age of 12 years (n = 231), (C) residents of Amsterdam, the Netherlands, with different ethnic backgrounds (n = 1,198), (D) men who have sex with men (MSM) (HIV positive and HIV negative) (n = 197), and (E) persons who use drugs (PWUD) (HIV positive and HIV negative) (n = 200). Anti-HEV immunoglobulin M (IgM) and immunoglobulin G (IgG) testing was performed using ELISA test (Wantai). HEV IgM seroprevalence was low across all study populations (<1% to 8%). The age and gender-adjusted HEV IgG seroprevalence was 24% among blood donors (reference group) and 9% among the vegetarian group (adjusted Relative Risk [aRR]:0.36, 95%CI:0.23-0.57). Among participants of different ethnic backgrounds, the adjusted HEV IgG seroprevalence was 16% among participants with a Dutch origin (aRR:0.64, 95%CI:0.40-1.02), 2% among South-Asian Surinamese (aRR:0.07, 95%CI:0.02-0.29), 3% among African Surinamese (aRR:0.11, 95%CI:0.04-0.34), 34% among Ghanaian (aRR:1.53, 95%CI:1.15-2.03), 19% among Moroccan (aRR:0.75, 95%CI:0.49-1.14), and 5% among Turkish (aRR:0.18, 95%CI:0.08-0.44) origin participants. First generation Moroccans had a higher risk for being IgG HEV seropositive compared to second generation Moroccan migrants. The statistical power to perform these analyses in the other ethnic groups was too low. In the MSM group the IgG HEV seroprevalence was 24% (aRR:0.99, 95%CI:0.76-1.29), and among PWUD it was 28% (aRR:1.19, 95%CI:0.90-1.58). The number of sexual partners in the preceding six months was not significantly associated with IgG HEV seropositivity in MSM. The association between HIV status and HEV seropositivity was significant in PWUD, yet absent in MSM. HIV viral load and CD4 cell count were not associated with HEV seropositivity in HIV positive MSM and PWUD. Vegetarians were significantly less often HEV seropositive. Ethnic origin influenced the risk for being IgG HEV seropositive. MSM and PWUD were not at higher risk for being IgG HEV seropositive than blood donors.


Quantifying long-term microelectrode array functionality using chronic in vivo impedance testing.
Long-term acquisition of high-quality neural recordings is a cornerstone of neuroprosthetic system design. Mitigating the experimental variability of chronically implanted arrays has been a formidable task because the sensor recording sites can be influenced by biotic and abiotic responses. Several studies have implicated changes in electrical interface impedance as a preliminary marker to infer electrode viability. Microelectrode impedance plays an important role in the monitoring of low amplitude and high-resolution extracellular neural signals. In this work, we seek to quantify long-term microelectrode array functionality and derive an impedance-based predictor for electrode functionality that correlates the recording site electrical properties with the functional neuronal recordings in vivo. High temporal resolution metrics of this type would allow one to assess, predict, and improve electrode performance in the future. In a large cohort of animals, we performed daily impedance measurements and neural signal recordings over long periods (up to 21 weeks) of time in rats using tungsten microwire arrays implanted into the somatosensory cortex. This study revealed that there was a time-varying trend in the modulation of impedance that was related to electrode performance. Single units were best detected from electrodes at time points when the electrode entered into the 40-150 KΩ impedance range. This impedance trend was modeled across the full cohort of animals to predict future electrode performance. The model was tested on data from all animals and was able to provide predictions of electrode performance chronically. Insight from this study can be combined with knowledge of electrode materials and histological analysis to provide a more comprehensive predictive model of electrode failure in the future.


Re-visiting protein-centric two-tier classification of existing DNA-protein complexes.
Precise DNA-protein interactions play most important and vital role in maintaining the normal physiological functioning of the cell, as it controls many high fidelity cellular processes. Detailed study of the nature of these interactions has paved the way for understanding the mechanisms behind the biological processes in which they are involved. Earlier in 2000, a systematic classification of DNA-protein complexes based on the structural analysis of the proteins was proposed at two tiers, namely groups and families. With the advancement in the number and resolution of structures of DNA-protein complexes deposited in the Protein Data Bank, it is important to revisit the existing classification. On the basis of the sequence analysis of DNA binding proteins, we have built upon the protein centric, two-tier classification of DNA-protein complexes by adding new members to existing families and making new families and groups. While classifying the new complexes, we also realised the emergence of new groups and families. The new group observed was where β-propeller was seen to interact with DNA. There were 34 SCOP folds which were observed to be present in the complexes of both old and new classifications, whereas 28 folds are present exclusively in the new complexes. Some new families noticed were NarL transcription factor, Z-α DNA binding proteins, Forkhead transcription factor, AP2 protein, Methyl CpG binding protein etc. Our results suggest that with the increasing number of availability of DNA-protein complexes in Protein Data Bank, the number of families in the classification increased by approximately three fold. The folds present exclusively in newly classified complexes is suggestive of inclusion of proteins with new function in new classification, the most populated of which are the folds responsible for DNA damage repair. The proposed re-visited classification can be used to perform genome-wide surveys in the genomes of interest for the presence of DNA-binding proteins. Further analysis of these complexes can aid in developing algorithms for identifying DNA-binding proteins and their family members from mere sequence information.


Origin of PCDDs in ball clay assessed with compound-specific chlorine isotope analysis and radiocarbon dating.
Polychlorinated dibenzo-p-dioxins (PCDDs) of high concentrations in a ball clay deposit from the Mississippi Embayment were found to be consistent with a natural abiotic and non-pyrogenic origin by investigation with bulk radiocarbon analysis, compound-specific chlorine isotope analysis (CSIA-delta37Cl) of octachlorodibenzo-p-dioxin (OCDD), and black carbon (BC) analysis. The conventional radiocarbon date of total organic carbon from a depth of approximately 10 m in three parallel cores ranged from 14 700 years to >48 000 years, indicating that the strata with elevated levels of PCDDs have remained isolated from recent anthropogenic input in these >40 Ma old clay sediments. The CSIA-delta37Cl of OCDD yielded a delta37Cl of -0.2 per thousandth, which is significantly higher than the postulated range for biotic chlorination by chloroperoxidase enzymes, -11 to -10 per thousandth, and falls within the known range for abiotic organochlorines, -6 to +3 per thousandth. The absence of correlations between concentrations of PCDDs and corresponding pyrogenic black carbon (BC), together with estimations of BC sorptive loadings and the absence of polychlorinated dibenzofurans (PCDFs), suggest that vegetation fires did not form these ball-clay PCDDs. Results from this study indicate that the high levels of the toxic and carcinogenic PCDDs found in kaolinite-bearing clays may result from natural abiotic formation via in situ surface-promoted reactions on the clay mineral, including a so-far unknown organic precursor, rather than being the result of anthropogenic contamination.


Evidence for the neuropeptide cholecystokinin as an antagonist of opiate analgesia.
The endogenous neuropeptide cholecystokinin, when administered systemically or perispinally, potently antagonizes opiate analgesia produced by foot shock and morphine. Nonopiate foot-shock analgesia is not reduced by this neuropeptide. The spinal cord appears to be a critical site of cholecystokinin action. These experiments suggest a physiological role for cholecystokinin as a specific opiate antagonist in analgesia-mediating systems. A similar mode of action may explain other behavioral effects of cholecystokinin, such as suppression of food intake.


Age dependence of subpopulations and functions of human peripheral lymphocytes.
The eventual dependency of a series of immune parameters on age has been studied in a material of 288 normal persons, divided into 2 sexes and with 16 persons in each 5-year age interval between 5 and 95 years, using a cryobiological freezing and storage system for lymphocytes with subsequent testing in large series. Lymphocyte transformation responses were studied after stimulation with a series of mitogens and specific antigens (PHA, PWM, PPD, Con A, SA, EC, CA and SK/SD), as well as with allogene cells in mixed lymphocyte culture. Values were found to decrease with increasing age. No age-dependency could be demonstrated for T and B lymphocytes using rosette formation tests. There was no difference between the two sexes. Thus, increasing age does not change the distribution between T and B lymphocytes, but does lead to a decrease in the function of the cell-mediated response.


[Study of exposure to and health effects of atmospheric metallic mercury pollution in an urban population of Poconé, Mato Grosso, Brazil]
This paper evaluates the levels of exposure to and health effects of metallic mercury emissions into the atmosphere by gold dealers in the town of Poconé, Mato Grosso State, Brazil. The project was based on the comparison of referred morbidity, clinical examination, and metallic mercury urinary concentrations in three population groups. The first group consisted of downtown residents who were exposed to metallic mercury emissions. The second group resided on the outskirts of the town and the third in an agricultural area. Urinary concentrations of metallic mercury showed highly significant differences between groups from downtown and the outskirts as compared to the control group. Investigation of individuals with high concentrations showed that exposure in the downtown area might have come from gold dealers' establishments. In the group from the town outskirts, exposure might have been from amalgam-smelting done inside homes. Referred morbidity data showed an increased proportion of complaints and alterations in clinical examinations by downtown residents as compared to the other groups.It was concluded that there was a possibility of exposure and health effects caused by metallic mercury for residents from the first two groups.


OCT minimum intensity as a predictor of geographic atrophy enlargement.
We determined whether the minimum intensity (MI) of the optical coherence tomography (OCT) A-scans within the retina can predict locations of growth at the margin of geographic atrophy (GA) and the growth rate outside the margin. The OCT scans were analyzed at baseline and 52 weeks. Expert graders manually segmented OCT images of GA. The 52-week follow-up scans were registered to the baseline scan coordinates for comparison. The OCT MI values were studied within a 180-μm margin around the boundary of GA at baseline. Baseline MI values were compared in areas of progression and nonprogression of the GA, and sensitivity and specificity were assessed for prediction of growth at the margin. Average MI values in the margins were compared to overall growth rates to evaluate the prediction of growth outside the margins. A statistically significant increase in MI (P < 0.05) was seen in areas of growth in 21/24 cases (88%), and 22/24 cases (92%) when the foveal subfield was excluded. Locations of growth within the margins at 52 weeks were predicted with 61% sensitivity and 61% specificity. The MI values correlated significantly with overall growth rate, and high and low growth rate subjects were identified with 80% sensitivity and 64% specificity. The MI may be increased at the margins of GA lesions before enlargement, which may indicate disruption or atrophy of the photoreceptors in these areas before GA becomes apparent. Increased MI may help predict areas of enlargement of GA, and may relate to overall growth rate and be a useful screening tool for GA. (ClinicalTrials.gov number, NCT00935883.).


Screening-preventable cervical cancer risks: evidence from a nationwide audit in Sweden.
The effectiveness of cervical cancer screening programs differs widely in different populations. The reasons for these differences are unclear. Routine and comprehensive audits have been proposed as an ethically required component of screening. We performed a nationwide audit of the effectiveness of the Swedish cervical cancer screening program. We identified all invasive cervical cancer cases that were diagnosed in Sweden from January 1, 1999, through December 31, 2001, and had been reported to the Swedish Cancer Registry (n = 1230 cases). We verified the diagnoses by histopathologic rereview and matched each case subject to five (population-based) age-matched control subjects who were identified from the National Population Register. The Pap smear screening histories for case and control subjects were reviewed for a 6-year period using the National Cervical Cancer Screening Register, which contains data on essentially all relevant cytological and histological diagnoses in Sweden. Odds ratios (ORs), and their 95% confidence intervals (CIs), of cervical cancer according to screening history were calculated in conditional logistic regression models. All statistical tests were two-sided. Women who had not had a Pap smear within the recommended screening interval had higher risk of cervical cancer than women who had been screened (OR = 2.52, 95% CI = 2.19 to 2.91). This risk was similarly increased for all age groups (P(homogeneity) = .96). The risk for non-squamous cell cervical cancers (OR = 1.59, 95% CI = 1.20 to 2.11) was also increased. Women who had not had a Pap smear within the recommended screening interval had a particularly high risk of advanced cancers (OR = 4.82, 95% CI = 3.61 to 6.44). Among women who had been screened within the recommended interval, those with abnormal Pap smears had a higher risk of cervical cancer than those with normal smears (OR = 7.55, 95% CI = 5.88 to 9.69) and constituted 11.5% of all women with cervical cancer. Nonadherence to screening intervals was the major reason for cervical cancer morbidity. The screening program was equally effective for women of all ages and was also effective against non-squamous cancers.


Cross-cultural structures of concentric and diametric dualism in Lévi-Strauss' structural anthropology: structures of relation underlying the self and ego relation?
The parallels between Jung's and Lévi-Strauss' concentric cross-cultural structures of the unconscious are highlighted. Lévi-Strauss' basic contrasts between concentric and diametric dualisms are developed into psychologically relevant differences regarding symmetry, connection and separation, and interaction between foreground and background structures respectively. These contrasts between concentric and diametric structures are applied as a common structural framework for understanding Jungian conceptions of the self, the ego and their relations, Freudian views of compensation and repetition in obsessional neurosis, and Winnicott's conception of a child's transitional object. Developing the contrasts between concentric and diametric structures reveals a compensatory relation between both structures. This supports an argument that concentric structures express the self and diametric structures express the ego in their mutual compensatory interrelation. Contrasting concentric with diametric structures challenges traditional Western logic, including Fordham's view that it is contradictory to treat the self as both centre and totality. It also develops an understanding of Jung's transcendent function which seeks to go beyond the ego-shadow opposition.


Specific lipoplex-mediated antisense against Bcl-2 in breast cancer cells: a comparison between different formulations.
G3139 is an antisense oligonucleotide (ODN) that can down-regulate bcl-2, thus potentially acting as a potent anticancer drug. However, effective therapy requires efficient ODN delivery, which may be achieved by employing G3139 lipoplexes. Yet, lipofection is a complex, multifactorial process that is still poorly understood. In order to shed more light on this issue, we prepared 18 different G3139 lipoplex formulations and compared them in terms of their capability to transfect MCF-7 breast cancer cells. Each formulation was composed of a cationic lipid and sometimes a helper lipid. The cationic lipid was either DOTAP (N-(1-(2,3-dioleoyloxy)propyl)-N,N,N-trimethylammonium chloride), DC-CHOL (3ss[N-(N',N'-dimethylaminoethane)carbamoyl]-cholesterol), or CCS (ceramide carbomoyl spermine). The helper lipid was either DOPC, DOPE, or cholesterol. Each lipid combination existed in two different structural forms--either large unilamellar vesicles (approximately 100 nm LUV) or unsized heterolamellar vesicles (UHV). Cell proliferation assays were used to evaluate the cytotoxicity of G3139 lipoplexes, control cationic lipid assemblies, and free G3139. Western blots were used to confirm the specific activity of G3139 as an anti-bcl-2 antisense agent. We determined that treatment of MCF-7 cells with G3139:CCS lipoplexes (UHV-derived) produced a maximal 50-fold improvement in antisense efficacy compared to treatment with free G3139. The other G3139 lipoplexes were not superior to free G3139. Thus, successful lipofection requires precise optimization of lipoplex lipid composition, structure, and concentration.


Activation of membrane receptors by a neurotransmitter conjugate designed for surface attachment.
The derivatization of surfaces with bioactive molecules is a research area of growing importance for cell and tissue engineering. Tetherable molecules used in such applications must contain an anchoring moiety as well as the biofunctional group, typically along with a spacer to prevent steric clashes between the target molecule and the tethering surface. Post-synaptic membrane receptors at chemical synapses in neural tissue mediate signaling to the post-synaptic neuron and are activated by the binding of diffusible neurotransmitter molecules released by the pre-synaptic neuron. However, little attention has been directed at developing neurotransmitter analogs that might retain functionality when tethered to a surface that could be interfaced with post-synaptic receptor proteins. Muscimol (5-aminomethyl-3-hydroxyisoxazole), an analog of GABA (gamma-aminobutryic acid), is a known potent agonist of GABA(A) and GABA(C) post-synaptic receptors found in retina and other central nervous system tissue. The present paper reports experiments testing the electrophysiological activity of "muscimol-biotin" on cloned GABA receptors expressed in Xenopus oocytes. This compound, which is potentially suitable for tethering at avidin-coated surfaces, consists of muscimol conjugated through an N-acyl linkage to a 6-aminohexanoyl chain that is distally terminated by biotin. We find that muscimol-biotin, as well as a structurally similar compound (muscimol-BODIPY) containing a bulky fluorophore at the distal end of the aminohexanoyl chain, exhibits substantial agonist activity at GABA(A) and GABA(C) receptors. Muscimol-biotin and other similarly biotinylated neurotransmitter analogs, in combination with surface functionalization using avidin-biotin technology, may be useful in applications involving the controlled activation of neuronal post-synaptic receptors by surface-attached molecules.


Beyond empathy: expanding expressions of caring.
In this paper, a model describing nurses' responses to patients who are suffering is presented. The nurse's level of engagement with the patient is affected by whether the caregiver is focused on him-/herself or on the sufferer (i.e. embodied with the patient) and whether the caregiver is responding reflexively or with a learned response. Four types of communication patterns are identified: engaged responses (first-level) are used in a connected relationship; when the nurse responses reflexively and is focused on him-/herself, the response is reflected; when the caregiver is patient-focused, a learned response is labelled a professional response; and a self-focused, learned response is labelled detached. Examples of each type of response are provided.


Evolution and diversity of clonal bacteria: the paradigm of Mycobacterium tuberculosis.
Mycobacterium tuberculosis complex species display relatively static genomes and 99.9% nucleotide sequence identity. Studying the evolutionary history of such monomorphic bacteria is a difficult and challenging task. We found that single-nucleotide polymorphism (SNP) analysis of DNA repair, recombination and replication (3R) genes in a comprehensive selection of M. tuberculosis complex strains from across the world, yielded surprisingly high levels of polymorphisms as compared to house-keeping genes, making it possible to distinguish between 80% of clinical isolates analyzed in this study. Bioinformatics analysis suggests that a large number of these polymorphisms are potentially deleterious. Site frequency spectrum comparison of synonymous and non-synonymous variants and Ka/Ks ratio analysis suggest a general negative/purifying selection acting on these sets of genes that may lead to suboptimal 3R system activity. In turn, the relaxed fidelity of 3R genes may allow the occurrence of adaptive variants, some of which will survive. Furthermore, 3R-based phylogenetic trees are a new tool for distinguishing between M. tuberculosis complex strains. This situation, and the consequent lack of fidelity in genome maintenance, may serve as a starting point for the evolution of antibiotic resistance, fitness for survival and pathogenicity, possibly conferring a selective advantage in certain stressful situations. These findings suggest that 3R genes may play an important role in the evolution of highly clonal bacteria, such as M. tuberculosis. They also facilitate further epidemiological studies of these bacteria, through the development of high-resolution tools. With many more microbial genomes being sequenced, our results open the door to 3R gene-based studies of adaptation and evolution of other, highly clonal bacteria.


Spatial dynamics within and between brain functional domains: A hierarchical approach to study time-varying brain function.
The analysis of time-varying activity and connectivity patterns (i.e., the chronnectome) using resting-state magnetic resonance imaging has become an important part of ongoing neuroscience discussions. The majority of previous work has focused on variations of temporal coupling among fixed spatial nodes or transition of the dominant activity/connectivity pattern over time. Here, we introduce an approach to capture spatial dynamics within functional domains (FDs), as well as temporal dynamics within and between FDs. The approach models the brain as a hierarchical functional architecture with different levels of granularity, where lower levels have higher functional homogeneity and less dynamic behavior and higher levels have less homogeneity and more dynamic behavior. First, a high-order spatial independent component analysis is used to approximate functional units. A functional unit is a pattern of regions with very similar functional activity over time. Next, functional units are used to construct FDs. Finally, functional modules (FMs) are calculated from FDs, providing an overall view of brain dynamics. Results highlight the spatial fluidity within FDs, including a broad spectrum of changes in regional associations, from strong coupling to complete decoupling. Moreover, FMs capture the dynamic interplay between FDs. Patients with schizophrenia show transient reductions in functional activity and state connectivity across several FDs, particularly the subcortical domain. Activity and connectivity differences convey unique information in many cases (e.g., the default mode) highlighting their complementarity information. The proposed hierarchical model to capture FD spatiotemporal variations provides new insight into the macroscale chronnectome and identifies changes hidden from existing approaches.


Histomorphometric analysis of salivary gland in wistar rats treated chronically with two benzodiazepines.
Benzodiazepines (BZDs), the most commonly prescribed psychotropic drugs with anxiolytic action, may cause hyposalivation. Therefore, this study sought to quantify the acini (N) in parotid glands of Wistar rats treated chronically with two BZDs (Lorazepam and Midazolan) and to verify the action of the pilocarpine when administered with these drugs. Ninety male Wistar rats were distributed in 9 groups according to the administration of: a) S30 - saline solution for 30 days; b) S60 - saline solution for 60 days; c) P60 - pilocarpine for 60 days; d) L30 - Lorazepam for 30 days; e) M30 - Midozolam for 30 days; f) LS60 - Lorazepam for 60 days and, after this period, 30 more days of saline solution; g) MS60 - Midazolam for 30 days and, after this period, 30 more days of saline solution; h) LP60 - Lorazepam and Pilocarpine for 60 days; i) MP60 - Midazolam and Pilocarpine for 60 days. A surgery was performed on the animals to remove the glands. After this, histological cuts were stained by hematoxylin and eosin, from which the N was quantified. The ANOVA and Games-Howell tests were used for statistical analysis. The L30 and M30 groups presented less N than did the S30 group (p<0.05). The LS60, MS60, and LP60 groups presented less N than did the S60 and P60 groups (p<0.05). No differences could be observed between the MP60 and S60 groups. The chronic administration of Midazolam and Lorazepam reduced acini, which may well have collaborated in the reduction of salivary flow previously verified. The association of Midazolam with Pilocarpine led to the reestablishment of acinar cells, which may have favored the restoration of the salivary flow formerly shown.


[Nurses, nursing technicians and assistants: who experiences more moral distress?].
To identify the frequency and intensity of moral distress experienced by nurses, technicians and nursing assistants who worked in hospitals in the South of Rio Grande do Sul State. A survey research was conducted with 334 nursing workers from three institutions, through a questionnaire of moral distress. Constructs were validated through factorial analysis and Cronbach's alpha: lack of competence of the working team, disrespect to the patient's autonomy, insufficient working conditions and therapeutic obstinacy. With descriptive statistics and analysis of variance, it was found that nurses and nursing assistants have higher perception of moral distress when compared to nursing technicians. Organizational questions and ways of communication influence lower perception of moral distress. Implementation of actions to favor coping, decision making and autonomy exercise from those workers.


Risk factors and long-term outcome for postoperative intra-abdominal infection after hepatectomy for hepatocellular carcinoma.
Intra-abdominal infection (IAI) after hepatectomy is an important morbidity. Identification of risk factors that could be avoided in the perioperative period may reduce the prevalence of IAI after hepatectomy for hepatocelluar carcinoma (HCC).Between January 1995 and December 2009, all patients with HCC who underwent curative liver resection were evaluated retrospectively. Long-term outcomes were compared in IAI patients and non-IAI patients after hepatectomy. Preoperative, intraoperative, and tumor-related factors that could be independent factors for postoperative IAI were identified.Of 622 patients with HCC, 24 patients (3.9%) had IAI after hepatectomy. Both median survival and survival of patients with postoperative IAI were shorter than those for non-IAI patients (P < .05). Upon univariate analysis followed by multivariate analyses, three independent predictors for IAI were identified: weight loss (odds ratio [OR], 3.27; 95% confidence interval [CI], 1.17-9.11; P = .024), liver cirrhosis (0.28, 0.12-0.67, .004), and operative time >300 minutes (3.44, 1.46-8.12, .005).IAI after hepatectomy affects outcome adversely. Preoperative weight loss, liver cirrhosis, and operative time >300 minutes are independent predictors of postoperative IAI.


Potential for involvement of Fas antigen/Fas ligand interaction in apoptosis of epithelial cells by intraepithelial lymphocytes in murine small intestine.
Intestinal epithelial cells (i-EC), which move to the villus tips from the crypts, rapidly die by apoptosis at the villus tips and are perpetually renewed at the crypts. To determine whether the Fas antigen (Fas)/Fas ligand (FasL) system is involved in the mechanism leading to apoptosis of i-EC, we examined the expression of Fas and FasL on the i-EC and intestinal intraepithelial lymphocytes (i-IEL) in normal mice. A high level of Fas was expressed on both the i-EC and i-IEL, whereas FasL was expressed in the i-IEL, especially in high-density fraction upon separation (high-density i-IEL), but not in the i-EC. The high-density i-IEL exhibited cytotoxicity against not only Fas transfectant but also the i-EC, and the cytotoxicity was inhibited by addition of Fas-Fragment c chimeric fusion protein. Thus, a significant fraction of i-IEL, such as high-density i-IEL, may partly contribute to induction of apoptosis in the effete i-EC via Fas/FasL interaction.


The effect of adding robot-assisted hand rehabilitation to conventional rehabilitation program following stroke: A randomized-controlled study.
This study aimed to investigate the effectiveness of adding robot-assisted hand therapy (HandTutor) to conventional rehabilitation program compared to a conventional rehabilitation program alone in stroke survivors. Between March 2012 and December 2012, a total of 33 stroke patients (21 males, 12 females; median age: 56 years; range, 38 to 73 years) were included in this prospective, randomized-controlled study. The patients were randomly divided into two groups as experimental (n=16) and control (n=17). Both groups received conventional rehabilitation for 3 h/day, for two days/week, totally for five weeks, while the experimental group received additional 1-hour robot-assisted hand therapy during each session. Outcome measures were the Fugl-Meyer Assessment, Box and Block Test, Nine-Hole Peg Test, Jebsen-Taylor Hand Function Test, grip strength, and pinch strength. All patients were assessed at baseline, at the end of the treatment, and three months after the treatment. Both groups showed statistically significant improvements in all the parameters (p<0.05). No significant differences were observed between the groups at any time points (p>0.05). The changes between baseline and three-month follow-up after the treatment revealed that adding robot-aided hand therapy led to greater changes in all the parameters related to functional activities and muscle strength, except for the Fugl-Meyer Assessment. Adding robot-assisted therapy to conventional rehabilitation may provide greater changes in upper extremity rehabilitation of subacute stroke patients compared to conventional rehabilitation program alone.


[Tryptase: a diagnostic marker in allergic diseases].
Mast cells play a central role in allergic diseases, following activation by means of immunologic mechanisms. Mast cell degranulation releases preformed and newly generated mediators and potential indicators of mast cell activation. Tryptase is the most useful marker of selective mast cell activation with regard to specific pathological states in which it can be applied with positive results, especially allergic diseases.


The airbag problem-a potential culprit for bench-to-bedside translational efforts: relevance for Alzheimer's disease.
For the last 20 years, the "amyloid cascade hypothesis" has dominated research aimed at understanding, preventing, and curing Alzheimer's disease (AD). During that time researchers have acquired an enormous amount of data and have been successful, more than 300 times, in curing the disease in animal model systems by treatments aimed at clearing amyloid deposits. However, to date similar strategies have not been successful in human AD patients. Hence, before rushing into further clinical trials with compounds that aim at lowering amyloid-beta (Aβ) levels in increasingly younger people, it would be of highest priority to re-assess the initial assumption that accumulation of Aβ in the brain is the primary pathological event driving AD. Here we question this assumption by highlighting experimental evidence in support of the alternative hypothesis suggesting that APP and Aβ are part of a neuronal stress/injury system, which is up-regulated to counteract inflammation/oxidative stress-associated neurodegeneration that could be triggered by a brain injury, chronic infections, or a systemic disease. In AD, this protective program may be overridden by genetic and other risk factors, or its maintenance may become dysregulated during aging. Here, we provide a hypothetical example of a hypothesis-driven correlation between car accidents and airbag release in analogy to the evolution of the amyloid focus and as a way to offer a potential explanation for the failure of the AD field to translate the success of amyloid-related therapeutic strategies in experimental models to the clinic.


Ultrastructural changes in gap junctions associated with CO2 uncoupling in frog atrial fibres.
The correlation between gap junction morphology and the state of electrical coupling was investigated in the frog auricle, which presents an atypical gap-junction organization. Electrical uncoupling of the tissue was achieved by perfusion with CO2-saturated Ringer medium. The tissue was fixed with glutaraldehyde and freeze-fractured before and during the application of CO2-saturated Ringer medium and after returning to the initial medium. The electrical tissue coupling was assayed by microelectrode recording just before fixation. At least 97% uncoupling was induced by CO2-saturated Ringer medium, as estimated from double sucrose gap experiments on several single atrial trabeculae. Several modifications were induced by CO2-saturated Ringer medium. A decrease in the number of particles per junctional assembly and dispersion of these assemblies in the plane of the membrane, indicate a decrease in the organization of the gap junctions. In parallel, loose clusters of particles became evident on the P-fracture face of the membrane. The size of the particles in these clusters was larger than the size of the background particles, and of the gap junction particles. They never corresponded with complementary pits on the E-fracture face. On return to the initial Ringer perfusion medium the cell coupling was reversed and the gap junction dispersion was also reversed. However, the gap junctions remained small. The relationship between these morphological modifications and the conducting state of the tissue is discussed.


The afterbirth of the clinic: a Foucauldian perspective on "House M.D." and American medicine in the 21st century.
Mirroring Michel Foucault's The Birth of the Clinic (1963), which describes the philosophical shift in medical discourse in the 19th and early 20th centuries, the Fox television series House M.D. illustrates the shift in medical discourse emerging today. While Dr. Gregory House is Foucault's modern physician made flesh -- an objective scientist who has perfected the medical gaze (le regard) and communicates directly with diseases instead of patients -- his staff act as postmodern foils. They provide a parable about the state of biomedicine, still steeped in modernity but forced into a postmodern, managed care world. House M.D., however, is more than a mere depiction of the modern-postmodern tension that exists in today's exam rooms. It is an indication of a transition period in American medicine. House M.D. nostalgically celebrates what once was and simultaneously questions what currently is, while what is about to be is in the midst of becoming.


Health-related quality of life trajectories in critical illness: Protocol for a Monte Carlo simulation study.
Health-related quality of life (HRQoL) is a patient-centred outcome increasingly used as a secondary outcome in critical care research. It may cover several important dimensions of clinical status in intensive care unit (ICU) patients that arguably elude other more easily quantified outcomes such as mortality. Poor associations with harder outcomes, conflicting data on HRQoL in critically ill compared to the background population, and paradoxical effects on HRQoL and mortality complicate the current operationalisation in critical care trials. This protocol outlines a simulation study that will gauge if the areas under the HRQoL trajectories could be a viable alternative. We will gauge the behaviour of the proposed HRQoL operationalisation through Monte Carlo simulations, under clinical scenarios that reflect a broad critical care population eligible for inclusion in a large pragmatic trial. We will simulate 15,360 clinical scenarios based on a full factorial design with the following seven simulation parameters: number of patients per arm, relative mortality reduction in the interventional arm, acceleration of HRQoL improvement in the interventional arm, the relative improvement in final HRQoL in the interventional arm, dampening effect of mortality on HRQoL values at discharge from the ICU, proportion of so-called mortality benefiters in the interventional arm and mortality trajectory shape. For each clinical scenario, we will simulate 100,000 two-arm trials with 1:1 randomisation. HRQoL will be sampled fortnightly after ICU discharge. Outcomes will include HRQoL in survivors and all patients at the end of follow-up; mean areas under the HRQoL trajectories in both arms; and mean difference between areas under the HRQoL trajectories and single-sampled HRQoLs at the end of follow-up. In the outlined simulation study, we aim to assess whether the area under the HRQoL trajectory curve could be a candidate for reconciling the seemingly paradoxical effects on improved mortality and reduced HRQoL while remaining sensitive to early or accelerated improvement in patient outcomes. The resultant insights will inform subsequent methodological work on prudent collection and statistical analysis of such data from real critically ill patients.


Consequences of Family Member Incarceration: Impacts on Civic Participation and Perceptions of the Legitimacy and Fairness of Government.
Political participation and citizens' perceptions of the legitimacy and fairness of government are central components of democracy. In this article, we examine one possible threat to these markers of a just political system: family member incarceration. We offer a unique glimpse into the broader social consequences of punishment that are brought on by a partner's or parent's incarceration. We argue that the criminal justice system serves as an important institution for political socialization for the families of those imprisoned, affecting their attitudes and orientations toward the government and their will and capacity to become involved in political life. We draw from ethnographic data collected by one of the authors, quantitative data from the National Longitudinal Study of Adolescent Health, and interviews with recently released male prisoners and their female partners. Our findings suggest that experiences of a family member's incarceration complicate perceptions of government legitimacy and fairness and serve as a barrier to civic participation.


Static and Dynamic Balance in Adults Undergoing Lumbar Spine Surgery: Screening and Prediction of Postsurgical Outcomes.
Balance and fall risk before and after lumbar surgery was assessed to determine whether balance at baseline predicts long-term postsurgical outcomes. Forty-three patients in the United States and Israel performed the single-leg stance (SLS) test, four square step test (FSST), and 8-foot up-and-go (8FUG) test before and 2 to 4 months after lumbar spine surgery. They completed the Oswestry Disability Index (ODI) and pain rating before and 12 months after lumbar surgery. From baseline to follow-up, the SLS time was 3.74 seconds longer (P = 0.01), the FSST time was 1.94 seconds faster (P < 0.001), and the 8FUG time was 1.55 seconds faster (P = 0.02). Before surgery, 26% of the patients were considered high fall risk according to the FSST and 51% according to the 8FUG. Postsurgery, all patients could complete the physical tests, but 26% remained at high fall risk according to the 8FUG and 7.5% according to the FSST. The three physical measures together explained 30% of the variance in postsurgical ODI scores (P = 0.02). Age was not correlated with performance. Risk of falling is higher than surgeons suspect. Balance tests (ie, SLS, FSST, and 8FUG) are quick and easy to administer. The findings support the importance of screening for balance and fall risk in adults undergoing lumbar spine surgery.


Low-Level Light Therapy Downregulates Scalp Inflammatory Biomarkers in Men With Androgenetic Alopecia and Boosts Minoxidil 2% to Bring a Sustainable Hair Regrowth Activity.
Low-level light therapies using visible to infrared light are known to activate several cellular functions, such as adenosine triphosphate and nitric oxide synthesis. However, few clinical observations report its biological consequences for skin and scalp homeostasis. Since scalp inflammation was recognized as a potential physiological obstacle to the efficacy of the reference hair regrowth drug Minoxidil in vivo and since perifollicular inflammation is the hallmark of about 50%-70% follicular units in androgenetic alopecia, we decided to investigate whether the anti-inflammatory activity of LLLT/GentleWaves® device were assigned to L'Oréal by Light BioScience L.L.C., Virginia Beach, VA (US) could enhance hair regrowth activity of Minoxidil. We conducted a first experimental clinical study on 64 men with androgenetic alopecia using LLLT/GentleWaves®, 590-nm predominant wavelength 70 seconds, specifically pulsed once per day, for 3 days, and we performed a whole-genome analysis of treated scalp biopsies. In a second clinical study, including 135 alopecic volunteers, we evaluated the hair regrowth activity in response to the upgraded LLLT/GentleWaves® device and Minoxidil. In the first clinical study, whole-genome analysis of treated scalp biopsies showed downregulation of scalp inflammatory biomarkers, such as AP1/FOSB messenger RNA (mRNA) and mir21, together with the disappearance of CD69 mRNA, specific to scalp-infiltrating T cells of about 50% of the studied volunteers prior to the LLLT/GentleWaves® treatment. In the second clinical study, we observed that LLLT/GentleWaves® was able to boost the hair regrowth activity of a Minoxidil 2% lotion to the extent of the highest concentration (5%) in terms of efficacy, number of responders, and perceived performance. Altogether, these observations suggest the potential benefit of LLLT/GentleWaves® as a noninvasive adjunctive technology for skin and scalp conditions, where a mild perifollicular inflammation is involved. Lasers Surg. Med. 2021. Copyright © 2021 Wiley Periodicals LLC.


The international society for developmental psychobiology Sackler symposium: early adversity and the maturation of emotion circuits--a cross-species analysis.
Early-life caregiving shapes the architecture and function of the developing brain. The fact that the infant-caregiver relationship is critically important for infant functioning across all altricial species, and that the anatomical circuits supporting emotional functioning are highly preserved across different species, suggests that the results of studies examining the role of early adversity and emotional functioning should be translatable across species. Here we present findings from four different research laboratories, using three different species, which have converged on a similar finding: adversity accelerates the developmental trajectory of amygdala-prefrontal cortex (PFC) development and modifies emotional behaviors. First, a rodent model of attachment learning associated with adversity is presented showing precocial disruption of attachment learning and emergence of heightened fear learning and emotionality. Second, a model of infant-mother separation is presented in which early adversity is shown to accelerate the developmental emergence of adult-like fear retention and extinction. Third, a model of early life adversity in Rhesus monkeys is presented in which a naturally occurring variation in maternal-care (abuse) is shown to alter the functioning of emotion circuits. Finally, a human model of maternal deprivation is presented in which children born into orphanages and then adopted abroad exhibit aberrant development of emotion circuits. The convergence of these cross-species studies on early life adversity suggests that adversity targets the amygdala and PFC and has immediate impact on infant behavior with the caregiver, and emotional reactions to the world. These results provide insight into mechanisms responsible for caregiver induced mental health trajectory alterations.


Urinary pepsinogen I as a tumor marker of stomach cancer after total gastrectomy.
The possibility that urinary pepsinogen I is a tumor marker of stomach cancer after total gastrectomy was examined. To decide the cutoff level of urinary pepsinogen I after total gastrectomy, urine samples from 15 patients who had undergone total gastrectomy for stomach cancer in the early or advanced stages and had been free from recurrence for more than 5 years were examined by pepsinogen I-specific radioimmunoassay. The mean concentration of urinary pepsinogen I was 17.5 +/- 7.4 ng/ml and the cutoff level of urinary pepsinogen after total gastrectomy was set at 32 ng/ml (mean + 2 SD). Twenty-two of 74 cases who had undergone total gastrectomy for stomach cancer were regarded as positive. And 20 of these 22 positive cases had definite clinical signs of recurrence of stomach cancer. There were only two false-positive cases. These results suggest that urinary pepsinogen I will be an useful tumor marker in detecting the recurrence of stomach cancer after total gastrectomy.


HIV-1 infection leads to increased HLA-E expression resulting in impaired function of natural killer cells.
HIV has evolved several strategies to evade recognition by the host immune system including down-regulation of major histocompatibility complex (MHC) class I molecules. However, reduced expression of MHC class I molecules may stimulate natural killer (NK) cell lysis in cells of haematopoietic lineage. Here, we describe how HIV counteracts stimulation of NK cells by stabilizing surface expression of the non-classical MHC class I molecule, HLA-E. We demonstrate enhanced expression of HLA-E on lymphocytes from HIV-infected patients and show that in vitro infection of lymphocytes with HIV results in up-regulation of HLA-E expression and reduced susceptibility to NK cell cytotoxicity. Using HLA-E transfected K-562 cells, we identified the well-known HIV T-cell epitope p24 aa14-22a as a ligand for HLA-E that stabilizes surface expression of HLA-E, favouring inhibition of NK cell cytotoxicity. These results propose HIV-mediated up-regulation of HLA-E expression as an additional evasion strategy targeting the antiviral activities of NK cells, which may contribute to the capability of the virus in establishing chronic infection.


Comparison of p25 presequence peptide and melittin. Red blood cell haemolysis and band 3 aggregation.
The 25 residue presequence (p25) for subunit IV of yeast cytochrome oxidase had previously been shown to possess structural and behavioural characteristics in common with the bee venom polypeptide, melittin. The present study extends the results of leakage experiments on model-membrane systems to the haemolysis of human erythrocytes, which both peptides are shown to accomplish in a manner sensitive to membrane potential. In addition, the laser flash-induced transient dichroism technique for measuring protein rotational diffusion has been used to show that both peptides aggregate band 3, the major integral membrane protein of the erythrocyte. Aggregation cannot be reversed by high ionic strength; this serves to differentiate these peptides from other positively charged species such as polylysine that aggregate band 3 at low ionic strength. These results suggest that aggregation of membrane proteins may possibly prove to be a feature of the interaction of p25 signal peptide with mitochondrial membranes.


ERC 2010 guidelines for adult and pediatric resuscitation: summary of major changes.
The new European Resuscitation Council (ERC) guidelines for cardiopulmonary resuscitation (CPR) published on October 18th, 2010, replace those published in 2005 and are based on the latest International Consensus on CPR Science with Treatment Recommendations (CoSTR). For both adult and pediatric resuscitation, the most important general changes include: the introduction of chest compression-only CPR in primary cardiac arrest as an option for rescuers who are unable or unwilling to perform expired-air ventilation; increased emphasis on uninterrupted, good-quality CPR and minimisation of both pre- and post-shock pauses during defibrillation. For adult resuscitation, the recommended chest compression depth and rate are 5-6 cm and 100-120 compressions per minute, respectively. Both a specific period of CPR before defibrillation during out-of-hospital resuscitation and use of endotracheal route for drug delivery during advanced life support are no longer recommended. During postresuscitation care, inspired oxygen should be titrated to obtain an arterial oxygen saturation of 94-98%, to avoid possible damage from hyperoxemia. In pediatric resuscitation, the role of pulse palpation for the diagnosis of cardiac arrest has been de-emphasised. The compression-to-ventilation ratio depends on the number of rescuers available, and a 30:2 ratio is acceptable even for rescuers with a duty to respond if they are alone. Chest compression depth should be at least 1/3 of the anterior-posterior chest diameter. The use of automated external defibrillators for children under one year of age should be considered.


Neuronal damage and inflammatory biomarkers are associated with the affective and chronic fatigue-like symptoms due to end-stage renal disease.
Many biochemical, immunological, and neuropsychiatric changes are associated with end-stage renal disease (ESRD). Neuronal damage biomarkers such as glial fibrillary acidic protein (GFAP), neurofilament light chain (NFL), S100 calcium-binding protein B (S100B), ionized calcium-binding adaptor molecule-1 (IBA1), and myelin basic protein (MBP) are among the less-studied biomarkers of ESRD. We examined the associations between these neuro-axis biomarkers, inflammatory biomarkers, e.g., C-reactive protein (CRP), interleukin (IL-6), IL-10, and zinc, copper, and neuropsychiatric symptoms due to ERSD. ELISA techniques were used to measure serum levels of neuronal damage biomarkers in 70 ESRD patients, and 46 healthy controls. ESRD patients have higher scores of depression, anxiety, fatigue, and physiosomatic symptoms than healthy controls. Aberrations in kidney function tests and the number of dialysis interventions are associated with the severity of depression, anxiety, fibro-fatigue and physiosomatic symptoms, peripheral inflammation, nestin, and NFL. Serum levels of neuronal damage biomarkers (NFL, MBP, and nestin), CRP, and interleukin (IL)-10 are elevated, and serum zinc is decreased in ESRD patients as compared with controls. The neuronal damage biomarkers NFL, nestin, S100B and MBP are associated with the severity of one or more neuropsychiatric symptom domains. Around 50 % of the variance in the neuropsychiatric symptoms is explained by NFL, nestin, S00B, copper, and an inflammatory index. The severity of renal dysfunction and/or the number of dialysis interventions may induce peripheral inflammation and, consequently, neurotoxicity to intermediate filament proteins, astrocytes, and the blood-brain barrier, leading to the neuropsychiatric symptoms of ESRD.


Early and late lesion-to-non-lesion ratio of thallium-201-chloride uptake in the evaluation of "cold" thyroid nodules.
Forty-nine consecutive patients with "cold" thyroid nodules were studied using early and late visual and semiquantitative measurements of 201Tl uptake in the nodule to differentiate benign from malignant nodules. The visual method compared 201Tl uptake in the nodule to the normal thyroid tissue. The semiquantitative method used a lesion-to-non-lesion (L/N) ratio of the same areas. Both measurements were carried out early (15 min) and late (3 hr) following 201Tl injection. The reproducibility of the method for the early and late measurements was tested for intraobserver and interobserver variability as well as for repeatability coefficients. The visual method resulted in 43% sensitivity and 79% specificity for the detection of malignant nodules. The L/N method showed that an early threshold of 1.55 chosen by receiver characteristic analysis had a sensitivity of 57% and a specificity of 86%, while the late ratio of 0.99 had a sensitivity of 100% and a specificity of 62%. It is concluded that a L/N 201Tl uptake method performed 3 hr following 201Tl injection is superior to a visual scoring method as well as to the early L/N 201Tl uptake in detecting malignant thyroid nodules.


Divergence and Dissonance in Residents' Reported and Actual Feedback to Faculty in a Military Context.
Trainees (e.g., residents) are an obvious and common source of feedback for faculty; however, gaps exist in our understanding of their experiences and practices of providing such feedback. To gain a deeper understanding, this study examined residents' beliefs about what feedback is important to provide, the kinds of feedback they report giving, and the feedback they actually gave. Descriptive statistics were used to analyze residents' perceptions and feedback behaviors (n = 42/96). Thematic analysis was used to analyze end-of-rotation faculty assessments from 2018 to 2019 (n = 559) to explore the actual written feedback residents provided to the faculty. The findings suggest that residents experience workload constraints (e.g., too many feedback requests), feel that their feedback is not valuable or relevant, and place conditions on when and what feedback is given (e.g., faculty agreeableness, prefer giving positively oriented feedback, and uncomfortable giving negative feedback). When comparing what feedback residents rated as important with the kinds of feedback they reported giving and actually gave, the findings also suggest that there were consistencies (e.g., clinical instruction and professionalism) and inconsistencies (e.g., evidence-based practice and medical knowledge) that may limit constructive feedback for faculty. Taken together, the findings suggest that trainee assessments of faculty may be insufficient as a primary source of feedback to support the improvement of faculty performance. Potential solutions are discussed.


Can disc diffusion susceptibility tests assess the antimicrobial activity of engineered nanoparticles?
The use of disc diffusion susceptibility tests to determine the antibacterial activity of engineered nanoparticles (ENPs) is questionable because their low diffusivity practically prevents them from penetrating through the culture media. In this study, we investigate the ability of such a test, namely the Kirby-Bauer disc diffusion test, to determine the antimicrobial activity of Au and Ag ENPs having diameters from 10 to 40 nm on Escherichia coli cultures. As anticipated, the tests did not show any antibacterial effects of Au nanoparticles (NPs) as a result of their negligible diffusivity through the culture media. Ag NPs on the other hand exhibited a strong antimicrobial activity that was independent of their size. Considering that Ag, in contrast to Au, dissolves upon oxidation and dilution in aqueous solutions, the apparent antibacterial behavior of Ag NPs is attributed to the ions they release. The Kirby-Bauer method, and other similar tests, can therefore be employed to probe the antimicrobial activity of ENPs related to their ability to release ions rather than to their unique size-dependent properties. Graphical abstract.


The experience of urban aboriginals with health care services in Canada: implications for social work practice.
This exploratory study investigates the experience of Canadian Urban Aboriginal persons as consumers of health care services. Results highlight significant gaps in the training, skills, and knowledge of health care providers to optimally serve their Aboriginal patients. Also, several programs which are potentially most problematic for Aboriginal patients are identified. The discussion outlines important roles for hospital social workers in improving the care provided to urban Aboriginal patients.


Humans Can Taste Glucose Oligomers Independent of the hT1R2/hT1R3 Sweet Taste Receptor.
It is widely accepted that humans can taste mono- and disaccharides as sweet substances, but they cannot taste longer chain oligo- and polysaccharides. From the evolutionary standpoint, the ability to taste starch or its oligomeric hydrolysis products would be highly adaptive, given their nutritional value. Here, we report that humans can taste glucose oligomer preparations (average degree of polymerization 7 and 14) without any other sensorial cues. The same human subjects could not taste the corresponding glucose polymer preparation (average degree of polymerization 44). When the sweet taste receptor was blocked by lactisole, a known sweet inhibitor, subjects could not detect sweet substances (glucose, maltose, and sucralose), but they could still detect the glucose oligomers. This suggests that glucose oligomer detection is independent of the hT1R2/hT1R3 sweet taste receptor. Human subjects described the taste of glucose oligomers as "starchy," while they describe sugars as "sweet." The dose-response function of glucose oligomer was also found to be indistinguishable from that of glucose on a molar basis.


Hypoglycaemia on and after admission in Kenyan children with severe malaria.
We investigated the pathophysiology of hypoglycaemia in severe malaria in African children, especially the potential importance of glycerol as a substrate for gluconeogenesis, and whether substrate limitation contributes to hypoglycaemia in severe disease. Of 171 children with moderate or severe malaria, 16% were hypoglycaemic on admission, while at least 9% of children with severe malaria treated with quinine and a concurrent 4% dextrose infusion had a definite episode of hypoglycaemia after admission. Blood levels of gluconeogenic precursors are as high (alanine and lactate) or higher (glycerol) in those with either hypoglycaemia on or after admission as they are in children never having an episode of hypoglycaemia. Among children with severe malaria, however, those having a definite episode of hypoglycaemia at some stage are more acidotic and have greater evidence of renal impairment than those who are never hypoglycaemic (mean base excess -14.4 vs. -7.2, p < 0.001, mean creatinine 97 vs. 64, p < 0.001 and mean urea 8.1 vs. 5.8, p = 0.03, respectively). These data do not support a role for reduced gluconeogenic substrate supply in the pathogenesis of hypoglycaemia in severe childhood malaria, but do support the hypothesis that gluconeogenesis is impaired. Commonly-used bedside blood glucose monitoring devices may overestimate blood glucose measurements in the normal range, and paradoxically may also seriously overestimate the frequency of hypoglycaemia.


Guidelines and mHealth to Improve Quality of Hypertension and Type 2 Diabetes Care for Vulnerable Populations in Lebanon: Longitudinal Cohort Study.
Given the protracted nature of the crisis in Syria, the large noncommunicable disease (NCD) caseload of Syrian refugees and host Lebanese, and the high costs of providing NCD care, the implications for Lebanon's health system are vast. The aim of this study was to evaluate the effectiveness of treatment guidelines and a mobile health (mHealth) app on quality of care and health outcomes in primary care settings in Lebanon. A longitudinal cohort study was implemented from January 2015 to August 2016 to evaluate the effectiveness of treatment guidelines and an mHealth app on quality of care and health outcomes for Syrian and Lebanese patients in Lebanese primary health care (PHC) facilities. Compared with baseline record extraction, recording of blood pressure (BP) readings (-11.4%, P<.001) and blood sugar measurements (-6.9%, P=.03) significantly decreased following the implementation of treatment guidelines. Recording of BP readings also decreased after the mHealth phase as compared with baseline (-8.4%, P=.001); however, recording of body mass index (BMI) reporting increased at the end of the mHealth phase from baseline (8.1%, P<.001) and the guidelines phase (7.7%, P<.001). There were a great proportion of patients for whom blood sugar, BP, weight, height, and BMI were recorded using the tablet compared with in paper records; however, only differences in BMI were statistically significant (31.6% higher in app data as compared with paper records; P<.001). Data extracted from the mHealth app showed that a higher proportion of providers offered lifestyle counseling compared with the counseling reported in patients' paper records (health diet counseling; 77.3% in app data vs 8.8% in paper records, P<.001 and physical activity counseling and 59.7% in app vs 7.1% in paper records, P<.001). There were statistically significant increases in all four measures of patient-provider interaction across study phases. Provider inquiry of medical history increased by 16.6% from baseline following guideline implementation and by 28.2% from baseline to mHealth implementation (P<.001). From baseline, patient report of provider inquiry regarding medication complications increased in the guidelines and mHealth phases by 12.9% and 59.6%, respectively, (P<.001). The proportion of patients reporting that providers asked other questions relevant to their illness increased from baseline through guidelines implementation by 27.8% and to mHealth implementation by 66.3% (P<.001). Follow-up scheduling increased from baseline to the guidelines phase by 20.6% and the mHealth phase by 39.8% (P<.001). Results from this study of an mHealth app in 10 PHC facilities in Lebanon indicate that the app has potential to improve adherence to guidelines and quality of care. Further studies are necessary to determine the effects of patient-controlled health record apps on provider adherence to treatment guidelines, as well as patients' long-term medication and treatment adherence and disease control.


CT diagnosis of basilar artery occlusion.
Basilar artery occlusion was diagnosed by high-resolution computed tomography (CT) in 11 cases. The normal basilar artery imaged on plain CT scans has an attenuation value not higher than that of whole blood. If the CT attenuation value of the vessel is higher than that of blood, basilar artery occlusion is probably present. The tentative diagnosis can be confirmed by comparison of the attenuation values on the pre- and postcontrast scans, preferably using multiple slices obtained by multiplane dynamic CT.


MiR-25 regulates apoptosis by targeting Bim in human ovarian cancer.
MicroRNAs (miRNAs) are emerging as a class of small regulatory RNAs whose alterations are implicated in the initiation and progression of human cancers. Our study showed that miR-25 was highly expressed both in clinical ovarian cancer samples and cell lines. Down-regulation of miR-25 in ovarian cancer cells induced apoptosis whereas overexpression of miR-25 enhanced cell proliferation. The effects of miR-25 abrogation were partly mediated by the intrinsic apoptosis pathway. Many pro-apoptotic proteins such as Bim, Bax and caspase-3 were up-regulated after transfection. Furthermore, luciferase assays demonstrated that Bim was the direct target of miR-25. Introducing Bim cDNA without 3'UTR abrogated miR-25-induced cell survival. Finally, there was an inverse relationship between Bim and miR-25 expression in ovarian cancer tissues. Taken together, these data indicate that miR-25 directly regulates apoptosis by targeting Bim in ovarian cancer and that miR-25 could be a potential therapeutic target for ovarian cancer intervention.


Regulation of renal laminin in mice with type II diabetes.
This study examines the regulation of renal laminin in the db/db mouse, a model of type II diabetes characterized by extensive remodeling of extracellular matrix. Immunohistochemistry demonstrated an increase in the contents of laminin chains including beta1 chain in the mesangium and tubular basement membranes at 1, 2, 3, and 4 mo of diabetes. Immunofluorescence with an antibody against the recently discovered laminin alpha5 chain showed that in the normal mouse, the protein had a restricted distribution to the glomerular and tubular basement membranes with scant expression in the mesangium of older mice. In the diabetic mouse, the laminin alpha5 chain content of the glomerular and tubular basement membranes was increased, with marked expression in the mesangium. Northern analysis revealed a significant decrease in the renal cortical contents of alpha5, beta1, and gamma1 chain mRNA in the diabetic mice compared to control, at each of the time points. In situ hybridization showed decreased abundance of alpha5 transcripts in the glomeruli of diabetic mice compared to nondiabetic controls. Analysis of mRNA changes by Northern and in situ hybridization studies demonstrated that the reduction in laminin transcripts involved both glomerular and tubular elements. These observations demonstrate that laminin accumulation in the db/db mice with type II diabetes is due to nontranscriptional mechanisms. Because previous investigations in rodents with type I diabetes have shown that the increase in renal laminin content was associated with a corresponding increment in laminin chain transcript levels, it appears that the mechanisms underlying augmentation in renal matrix laminin content may be distinct in the two types of diabetes.


Interaction of propranolol with model phospholipid membranes. Monolayer, spin label and fluorescent spectroscopy studies.
The interaction of propranolol with model phospholipid membranes was studied using various experimental techniques. The partition coefficient of propranolol in the negatively charged membranes of vesicles prepared from phosphatidylserine and phosphatidic acid was found to be more than 20-times higher than in neutral phosphatidylcholine membranes. Preferential interaction of propranolol with acidic phospholipid membranes was confirmed using the monolayer compression isotherm technique and the spin-labelling method. Phosphatidylserine monolayers were markedly expanded even at a relatively low drug concentration (5 . 10(-6) M). In contrast, the effect of propranolol on phosphatidylcholine monolayers was much smaller, being detectable only at a higher concentration of the drug (1 . 10(-4) M). Spin-labeling experiments show that propranolol exerts marked ordering effect on bilayers prepared from acidic phospholipids and does not change the order parameter of phosphatidylcholine membranes. The dependence of the propranolol fluorescence spectrum on the polarity of the solvent allowed us to identify the intercalation region of the drug in the membrane. The fluorophore moiety of propranolol was found to be localized in the lipid polar head groups region of the bilayer. The role of electrostatic and hydrophobic effects in propranolol-membrane interaction is discussed and the effect of propranolol on the ordering of phospholipid bilayers is compared with the effects of other anesthetic-like molecules.


CytoML for cross-platform cytometry data sharing.
CytoML is an R/Bioconductor package that enables cross-platform import, export, and sharing of gated cytometry data. It currently supports Cytobank, FlowJo, Diva, and R, allowing users to import gated cytometry data from commercial platforms into R. Once data are available in R, the data can be further manipulated. For example it can be combined with other computational and analytic approaches, and the results can be exported to FlowJo or Cytobank to be explored by researchers using those platforms. We demonstrate how CytoML and related R packages can be used as a tool to import, modify and export several samples stained with the T cell panel from the FlowCAP IV Lyoplate data set. Once imported, the gating is modified using computational approaches, and exported for visualization in Cytobank and FlowJo. We further show how CytoML can be used to import gated data from a publicly accessible mass cytometry experiment from Cytobank. CytoML is the only tool that allows such sharing of gated cytometry data between researchers working across different platforms, and it will serve as a useful tool for validating and verifying the reproducibility of analyses. © 2018 The Authors. Cytometry Part A published by Wiley Periodicals, Inc. on behalf of International Society for Advancement of Cytometry.


Membrane-associated IL 1-like activity on rat dendritic cells.
The secretion of interleukin 1 (IL 1) by rat dendritic cells (DC) was studied in relation to their ability to induce the production of interleukin 2 (IL 2) and to induce IL 2 responsiveness. IL 1 (or IL 1-like activity) was measured by its capacity to enhance IL 2 production by EL4 cells. In contrast to peritoneal exudate cells (PEC) or splenic adherent cells, DC from thoracic duct lymph (TD-DC) or from spleen did not secrete detectable amounts of IL 1 on stimulation with LPS/Silica. However, TD-DC and splenic DC were able to enhance IL 2 production by EL4 cells directly, and were only two times less effective than PEC. By preventing cell-to-cell contact between stimulator cells and EL4 cells, it was demonstrated that most of the IL 2-inducing activity of TD-DC and PEC was associated with the cell membrane. Treatment with 1% paraformaldehyde (PFA) to abolish metabolic activity resulted in a 50% decrease (or inactivation) of IL 2-inducing activity of TD-DC in the EL4 assay. Moreover, UVB-irradiation (300 mJ/cm2) of TD-DC, which has been described to inhibit the release of IL 1 by macrophages, caused a 70% decrease in IL 2-inducing activity. In a primary allogeneic mixed leukocyte reaction, neither PFA-treated TD-DC nor UV-irradiated TD-DC were able to induce T cell proliferation or IL 2 production. The cells were, however, able to induce IL 2 responsiveness, i.e., T cell proliferation in the presence of excess human recombinant IL 2. The finding that IL 1 enhanced T cell responses to PFA-treated or UV-irradiated TD-DC in the absence and in the presence of excess IL 2 indicates that loss of stimulatory activity of TD-DC may be due in part to loss or inactivation of IL 1. These results suggest that membrane-associated structures, that are identical to or mimic IL 1, are involved in the activation of T cells by DC.


Colony-stimulating factor (CSF) in the uterus of the pregnant mouse.
During the growth of the pregnant uterus of inbred Balb/c mice uterine colony-stimulating factor (CSF) content increased 800-fold. This corresponded to a 75-fold increase in CSF concentration. The size of the increase was the same in the uteri of inbred Balb/c mice and the uteri of F1 hybrid C57Bl/Balb/c mice mated with F1 males. It was about four times greater in these uteri than it was in the uteri of randomly mated TO mice. After unilateral Fallopian tubal ligation of TO mice the concentration of CSF was as great in the non-gravid uterine horns as it was in the gravid uterine horns. Physicochemical characterization of CSF from extracts of pregnant uterus showed that it differed from that found in foetal extracts and that found in the circulation. Its function in the pregnant uterus is discussed.


Incidence and risk factors for hepatocellular carcinoma after solid organ transplantation.
Solid organ transplant recipients commonly are infected with hepatitis viruses, are immunosuppressed, and have other potential hepatocellular carcinoma (HCC) risk factors. We studied de novo HCC incidence arising after transplant using U.S. registry data (223,660 recipients, 1987-2005). We used proportional hazards regression to identify HCC risk factors and calculated standardized incidence ratios (SIRs) to compare HCC risk with that in the general population. Based on 74 cases reported by transplant centers to the registry, HCC incidence was 6.5 per 100,000 person-years among kidney, heart, and lung (non-liver) recipients and 25 per 100,000 person-years among liver recipients. Hepatocellular carcinoma incidence among non-liver recipients was independently associated with hepatitis B surface antigenemia (hazard ratio [HR] 9.7, 95% confidence interval [CI] 2.8-33), hepatitis C virus (HCV) infection (HR 6.9, 95% CI 2.5-19), and diabetes mellitus (HR 2.8, 95% CI 1.2-6.6). Among liver recipients, HCC incidence was associated with advancing age (P<0.001), male sex (HR 4.6, 95% CI 1.4-16), HCV infection (HR 3.1, 95% CI 1.3-7.2), and diabetes mellitus (HR 2.7, 95% CI 1.2-6.2). Among non-liver recipients, overall HCC incidence was similar to the general population (SIR 0.8) but elevated among those with HCV (3.4) or hepatitis B surface antigenemia (6.5). Hepatocellular carcinoma incidence among liver transplant recipients was elevated overall (SIR 3.4) and especially among those with HCV (5.0) or diabetes mellitus (6.2). Hepatocellular carcinoma incidence is elevated among liver transplant recipients and subsets of non-liver recipients. These risk factors indicate the need for improved control of viral hepatitis after solid organ transplantation.


The AGPase Family Proteins in Banana: Genome-Wide Identification, Phylogeny, and Expression Analyses Reveal Their Involvement in the Development, Ripening, and Abiotic/Biotic Stress Responses.
ADP-glucose pyrophosphorylase (AGPase) is the first rate-limiting enzyme in starch biosynthesis and plays crucial roles in multiple biological processes. Despite its importance, AGPase is poorly studied in starchy fruit crop banana (Musa acuminata L.). In this study, eight MaAGPase genes have been identified genome-wide in M. acuminata, which could be clustered into the large (APL) and small (APS) subunits. Comprehensive transcriptomic analysis revealed temporal and spatial expression variations of MaAPLs and MaAPSs and their differential responses to abiotic/biotic stresses in two banana genotypes, Fen Jiao (FJ) and BaXi Jiao (BX). MaAPS1 showed generally high expression at various developmental and ripening stages and in response to abiotic/biotic stresses in both genotypes. MaAPL-3 and -2a were specifically induced by abiotic stresses including cold, salt, and drought, as well as by fungal infection in FJ, but not in BX. The presence of hormone-related and stress-relevant cis-acting elements in the promoters of MaAGPase genes suggests that MaAGPases may play an important role in multiple biological processes. Taken together, this study provides new insights into the complex transcriptional regulation of AGPases, underlying their key roles in promoting starch biosynthesis and enhancing stress tolerance in banana.


[Nutrition mistakes in patients with nonalcoholic fatty liver disease and the ways of correction].
THE AIM OF REVIEW: To verify the role of nutrition in development of Nonalcoholic Fatty Liver Disease in patients with metabolic syndrome. The article contains main conceptions of etiology and pathogenesis of Nonalcoholic Fatty Liver Disease. Spesial attention gives to the role of nutrition in development of this case. The are own dates presented, which shows relationship between degree of obesity, factual nutrition and expression of morphological changes in liver in patients with Nonalcoholic Fatty Liver Disease. Nutrition mistakes in patients with Nonalcoholic Fatty Liver Disease are: excess of energy, animal proteins and fats, deficit of nutrition fibres, carbohydrates, antioxidants, vitamins B1, B2, PP. The main directions of diet in patients with Nonalcoholic Fatty Liver Disease.


Hypoglycemic effect of Lentinus strigosus (Schwein.) Fr. crude exopolysaccharide in streptozotocin-induced diabetic rats.
ABSTRACT This study reports the hypoglycemic effects of the crude exopolysaccharide (EPS) produced from submerged mycelial culture of Lentinus strigosus (Schwein.) Fr. (Family Polyporaceae) in streptozotocin (STZ)-induced diabetic rats. In a dose-dependent study, diabetic rats were treated with EPS at doses of 50-150 mg/kg of body weight for 7 days. Serum glucose and plasma insulin levels were measured in normal, STZ-induced diabetic, and EPS-treated diabetic rats. Following oral administration of EPS dosages for 7 days, the serum glucose levels in the STZ-induced diabetic rats were reduced up to 21.1% at the dose of 150 mg/kg of body weight. The results revealed that orally administered L. strigosus EPS, at the dose of 150 mg/kg, exhibited a considerable hypoglycemic effect in STZ-induced diabetic rats. Plasma insulin levels of STZ-induced diabetic rats decreased as compared to control group rats (P < .05). Although insulin levels slightly increased in the EPS-treated groups the increase was not statistically significant. The hypoglycemic potential of the EPS was further supported by histological observations of pancreatic islets of Langerhans.


Spontaneous solid-solid interface melting driven by concentration gradient.
The contact of heterogeneous materials with different atomic structures and concentrations becomes omnipresent in modern materials. The differences across the interface introduce various gradients that could alter thermodynamic and kinetic behaviors of the materials. Here, we report a spontaneous melting of the interface formed by a crystalline metal and an amorphous solid at the temperature below their respective equilibrium melting temperatures. The transformation can even become continuous with disappearance of all known features of the first-order melting transition. We show that the change in the nature of melting in the interface region is caused by random disordering induced by interdiffusing atomic elements or impurities in the crystalline phase and the presence of a strong concentration gradient constrained by the sample geometry.


Frequency of silent myocardial ischemia with 12-lead ST segment monitoring in the coronary care unit: are there sex-related differences?
Ischemia that occurs in the coronary care unit (CCU), whether symptomatic or silent, is associated with significant in-hospital and out-of-hospital complications. Studies have reported that more than 90% of ischemic episodes are silent in patients with unstable angina who are treated in the CCU with maximal medical therapy. Prior reports indicate that women complained more frequently of chest pain than men did. The aim of this study was to compare the frequency of silent myocardial ischemia in men versus women with use of continuous 12-lead ST segment monitoring in the CCU. A secondary goal was to determine whether silent ischemia was associated with less ST segment deviation as compared with symptomatic ischemia. Patients admitted for treatment of acute coronary syndrome in the CCU and who subsequently had 1 or more ischemic events during their monitoring period were selected for this analysis. All patients were continuously monitored (42.5 hours +/- 37.6) in the CCU with the EASI (Zymed Medical Instruments, Camarillo, Calif) 12-lead electrocardiogram (ECG) system that derives 12 leads with use of 3 information channels and 5 electrodes. Of 491 patients, 128 (91 men and 37 women) had at least 1 episode of transient myocardial ischemia. Men and women did not differ in their proportion of chest pain during ischemia (men 27% and women 21%, NS). For both men and women, ST segment deviation was significantly greater during symptomatic ischemia compared with silent ischemia. There are no sex-related differences in ischemic events in the CCU in regards to the variables of chest pain and ST magnitude. Therefore, because chest pain is not a reliable indicator of myocardial ischemia in the CCU, regardless of sex, patients should be adequately monitored for ischemic events.


The ionic requirements for the production of action potential in Achatina fulica Ferussac neuron.
The ionic requirement for the production of directly elicited action potentials of a tonically auto-active neuron (TAN) in the subesophageal ganglia of the giant African snail, Achatina fulica Ferussac, was studied electrophysiologically. Calcium free Ringer solution containing 1 mM EDTA reversibly abolished the directly elicited action potential. Verapamil (10 micrograms/ml) or cocaine (4 mg/ml) decreased both amplitude and Vmax of the action potentials. The amplitude of the action potential was also slightly decreased in sodium free choline Ringer. However, tetrodotoxin did not significantly affect either the amplitude or Vmax of the directly elicited action potentials. The results suggest that the ionic requirement for generating action potential in snail neuron is not an ordinary sodium spike. Both calcium and sodium ions may participate in carrying charges across the membrane of the action potential.


Engineering bacterial surface interactions using DNA as a programmable material.
The diverse surface interactions and functions of a bacterium play an important role in cell signaling, host infection, and colony formation. To understand and synthetically control the biological functions of individual cells as well as the whole community, there is growing attention on the development of chemical and biological tools that can integrate artificial functional motifs onto the bacterial surface to replace the native interactions, enabling a variety of applications in biosynthesis, environmental protection, and human health. Among all these functional motifs, DNA emerges as a powerful tool that can precisely control bacterial interactions at the bio-interface due to its programmability and biorecognition properties. Compared with conventional chemical and genetic approaches, the sequence-specific Watson-Crick interaction enables almost unlimited programmability in DNA nanostructures, realizing one base-pair spatial control and bio-responsive properties. This highlight aims to provide an overview on this emerging research topic of DNA-engineered bacterial interactions from the aspect of synthetic chemists. We start with the introduction of native bacterial surface ligands and established synthetic approaches to install artificial ligands, including direct modification, metabolic engineering, and genetic engineering. A brief overview of DNA nanotechnology, reported DNA-bacteria conjugation chemistries, and several examples of DNA-engineered bacteria are included in this highlight. The future perspectives and challenges in this field are also discussed, including the development of dynamic bacterial surface chemistry, assembly of programmable multicellular community, and realization of bacteria-based theranostic agents and synthetic microbiota as long-term goals.


Syntheses, structures, anomalous phase transition and optical properties of two new polymorphic α- and β-LiMoPO6.
New polymorphous phases, α- and β-LiMoPO6, have been successfully synthesized by the high temperature solution technique and their structures have been determined by single crystal X-ray diffraction. α-LiMoPO6 crystallizes in the orthorhombic space group Pbcn (No. 60) with a = 12.1141(4) Å, b = 8.9251(3) Å and c = 8.7389(3) Å, while β-LiMoPO6 crystallizes in the monoclinic space group P21/c (No. 14) with a = 6.3441(3) Å, b = 7.5949(3) Å, c = 9.3430(4) Å and β = 94.546(4)°. Both structures exhibit a similar three-dimensional (3D) framework composed of MoO6 octahedra and PO4 tetrahedra. Interestingly, an anomalous phase transition, i.e. the high-temperature β-LiMoPO6 phase exhibiting larger density than the low-temperature α-LiMoPO6, has been observed. Detailed structural analyses show that the anomalous phase transition mainly originates from the 'straightened' effect of the zigzag [MoO3O3PO]∞ chains in their structures. Furthermore, the optical and thermal properties of two compounds are also reported.


Controlled synthesis of high-quality PbS star-shaped dendrites, multipods, truncated nanocubes, and nanocubes and their shape evolution process.
Well-defined single-crystalline PbS nano- and microstructures including dendrites, multipods, truncated nanocubes, and nanocubes were synthesized in high yield by a simple solution route. Novel star-shaped PbS dendrites with six symmetric arms along the 100 direction, each of which shows one trunk (long axis) and four branches (short axes), have been achieved using Pb(AC)2 and thioacetamide (TAA) as precursors, under the molar ratio Pb(AC)2/TAA = 2/1, at initial reaction temperature 80 degrees C, refluxing for 30 min at 100 degrees C, in the presence of cetyltrimethylammonium bromine (CTAB). The "nanorods" in each branch are parallel to each other in the same plane and are perpendicular to the trunk. The truncated nanocubes mainly bounded by the {100} plane were prepared under a different Pb(AC)2/TAA molar ratio, at initial reaction temperature 40 degrees C, refluxing for 12 h at 100 degrees C. Based on the systematic studies on their shape evolution, a possible growth mechanism of these PbS nano- and microstructures was proposed. The shapes of PbS nanocrystals with face-centered cubic (fcc) structure are mainly determined by the ratio (R) between the growth rates along the (100) and (111) directions. The Pb(AC)2/TAA molar ratio and the initial reaction temperature influence the growth ratio R in the formation of PbS nuclei at an early stage, which results in the final morphology of PbS nanocrystals. Under the current experimental conditions, we can control the PbS shape evolution by simply tuning the molar ratio, the initial reaction temperature, and the period of reaction. Based on the systematic studies on the shape evolution, this approach is expected to be employed for the control-shaped synthesis of other fcc structural semiconductor nanomaterials. The photoluminescence properties were investigated and the prepared nano- and microstructures displayed a very strong luminescence around 600-650 nm at room temperature.


Preclinical Studies of OBI-999: A Novel Globo H-Targeting Antibody-Drug Conjugate.
Globo H (GH), a hexasaccharide, is expressed at low levels in normal tissues but is highly expressed in multiple cancer types, rendering it a promising target for cancer immunotherapy. OBI-999, a novel antibody-drug conjugate, is derived from a conjugation of a GH-specific mAb with a monomethyl auristatin E (MMAE) payload through a site-specific ThioBridge and a cleavable linker. OBI-999 high homogeneity with a drug-to-antibody ratio of 4 (>95%) was achieved using ThioBridge. OBI-999 displayed GH-dependent cellular internalization and trafficked to endosome and lysosome within 1 and 5 hours, respectively. Furthermore, OBI-999 showed low nanomolar cytotoxicity in the assay with high GH expression on tumor cells and exhibited a bystander killing effect on tumor cells with minimal GH expression. Tissue distribution indicated that OBI-999 and free MMAE gradually accumulated in the tumor, reaching maximum level at 168 hours after treatment, whereas OBI-999 and free MMAE decreased quickly at 4 hours after treatment in normal organs. Maximum MMAE level in the tumor was 16-fold higher than in serum, suggesting that OBI-999 is stable during circulation and MMAE is selectively released in the tumor. Excellent tumor growth inhibition of OBI-999 was demonstrated in breast, gastric, and pancreatic cancer xenograft or lung patient-derived xenograft models in a dose-dependent manner. The highest nonseverely toxic dose in cynomolgus monkeys is 10 mg/kg determined by a 3-week repeated-dose toxicology study demonstrating an acceptable safety margin. Taken together, these results support further clinical development of OBI-999, which is currently in a phase I/II clinical study in multiple solid tumors (NCT04084366). OBI-999, the first GH-targeting ADC, displayed excellent tumor inhibition in animal models across multiple cancer types, including breast, gastric, pancreatic, and lung cancers, warranting further investigation in the treatment of solid tumors.


Long-term quality of life of donors after living donor liver transplantation.
The aims of this study were to investigate the long-term effects of living donor liver transplantation (LDLT) on the health-related quality of life (HRQOL) of donors with the Short Form 36 health survey and to determine the risk factors for poor outcomes. Between June 1990 and June 2004, LDLT was performed 1000 times at Kyoto University Hospital. In July 2005, 997 of the 1000 donors were contacted by mail so that data on their HRQOL could be collected. In all, 578 donors responded (ie, there was a 58.0% response rate). The norm-based HRQOL scores for donors were better than the scores for Japanese norms across all time periods. All scores were similar for left lobe donors (n = 367) and right lobe donors (n = 211). For all donors, a multivariate logistic regression analysis revealed that age, the number of months until recovery to the preoperative health status, hospital visits due to donation-related symptoms, rest from work related to donation in the past month, and the existence of 2 or more comorbidities were significantly associated with decreased HRQOL scores. Postoperative complications and recipient mortality were not predictors of poor HRQOL. In conclusion, HRQOL was better for both right lobe donors and left lobe donors versus the Japanese norm population in the long term (mean postdonation period = 6.8 years). However, the prolongation of symptoms or sequelae related to donation lowered mental health or social functioning. The emergence of comorbidities after donation also significantly affected HRQOL in the long term. Careful follow-up and sustained counseling are required for donors with risk factors for lower HRQOL.


Quintessential adjustment of the cosmological constant
We construct a time dependent adjustment mechanism for the cosmological "constant" which could be at work in a late Friedmann-Robertson-Walker universe dominated by quintessence and matter. It makes use of a Brans-Dicke field that couples to the evolving standard-model vacuum energy density. Our explicit model possesses a stable late-time solution with a fixed ratio of matter and field energy densities. No fine-tuning of model parameters or initial conditions is required.


Unilateral Endogenous Bacterial Endophthalmitis Post-Coronavirus Disease-19 in an Healthy Asian Indian Male.
Coronavirus disease 2019 (COVID-19) is associated with ocular involvement either during or after the infection. These include conjunctivitis, conjunctival hyperemia, chemosis, epiphora, reactivation of anterior uveitis, or presenting as anterior sclero-uveitis, cotton wool spots, retinal hemorrhages, retinal artery/vein occlusion, ophthalmic artery occlusion, panuveitis, papillophlebitis, central serous retinopathy, presumed fungal endophthalmitis, and multifocal chorioretinitis. A 47-year-old Asian Indian male was diagnosed with COVID-19 and had no other systemic history of note at the time of admission. Three weeks later, he developed sudden loss of vision in the right eye (OD). Visual acuity in OD was perception of light. OD had features of endophthalmitis. OD underwent pars plana vitrectomy with intravitreal antibiotics. Anterior chamber tap for fungal culture and polymerase chain reaction for panfungal genome was negative. Culture of ocular specimens did not reveal bacterial growth. Vitreous sample showed few Gram-positive cocci in singles and pairs with no evidence of fungal elements. Polymerase chain reaction for eubacterial genome was positive. He was treated with topical and systemic antibiotics and steroids. Final follow-up 6 weeks later, OD had a best-corrected visual acuity which was 20/200 with a quiet anterior chamber, cataract, with a macular traction and reduced sub retinal exudates and fluid. Post-COVID-19 sequelae causing sight-threatening manifestations as illustrated by this case report needs early recognition and prompt treatment to achieve a favorable visual outcome.


Influenza. Cost of illness and considerations in the economic evaluation of new and emerging therapies.
Influenza infection has been a burden to humans for thousands of years. Despite the fact that epidemics could be predicted with regularity, the lack of available prevention or treatment measures left humankind vulnerable to the harmful effects of this ubiquitous virus. While the pandemics of 1918 and 1957 are recent examples of the devastation that influenza may inflict, even in a typical year influenza infection and related complications cause significant morbidity and mortality. The development of an influenza vaccine during the 1940s marked a major turning point in the management of this disease. Vaccination of the elderly and other high risk patients has been shown to reduce morbidity and mortality and to be a worthwhile investment from an economic perspective. Despite these benefits, vaccine use in this group remains suboptimal. The role of annual vaccination for individuals at lower risk for influenza-related complications remains controversial. While prevention by vaccination is relatively straightforward, the treatment of symptomatic influenza-like illness with medication is more complicated. Differentiating symptoms caused by the influenza viruses from those caused by other common viruses is difficult. Currently available tests to document influenza as the cause of illness are either too expensive, too inaccurate or too time consuming to impact treatment. Symptom-based diagnosis remains the most commonly used strategy in clinical practice. The approval of the neuraminidase inhibitors (NIs)--zanamivir and oseltamivir--remind healthcare providers of the difficulties in diagnosing and treating influenza. NIs have been shown to reduce the duration of symptoms of individuals infected with influenza when prescribed within the first 2 days of symptoms. Whether these innovative agents are cost effective, however, requires a more detailed understanding of the benefits that these agents may offer above and beyond existing therapies. In this review, we examine the burden of influenza infection, diagnostic challenges and the clinical and economic impact of available interventions. Clinical controversies and potential areas for further investigation are also explored.


Iron-Catalyzed Stereoconvergent 1,4-Hydrosilylation of Conjugated Dienes.
Stereoconvergent transformation of E/Z mixtures of olefins to products with a single steric configuration is of great practical importance but hard to achieve. Herein, we report an iron-catalyzed stereoconvergent 1,4-hydrosilylation reactions of E/Z mixtures of readily available conjugated dienes for the synthesis of Z-allylsilanes with high regioselectivity and exclusive stereoselectivity. Mechanistic studies suggest that the reactions most likely proceed through a two-electron redox mechanism. The stereoselectivity of the reactions is ultimately determined by the crowded reaction cavity of the α-diimine ligand-modified iron catalyst, which forces the conjugated diene to coordinate with the iron center in a cis conformation, which in turn results in generation of an anti-π-allyl iron intermediate. The mechanism of this stereoconvergent transformation differs from previously reported mechanisms of other related reactions involving radicals or metal-hydride species.