Examining Participant Dosage and Skill Utilization Associated with Receipt of a Perinatal Depression Preventive Intervention.
This study assessed participant, facilitator, and program-level characteristics associated with intervention dosage among women receiving an evidence-based perinatal depression preventive intervention, Mothers and Babies (MB). We also explored how intervention dosage affected the use and maintenance of core skills taught in the six-session group-based intervention. We conducted a secondary analysis of data from a cluster-randomized controlled trial in which 679 women enrolled in home visiting (HV) programs received MB prenatally. High dose of intervention was defined as attendance at > 50% of MB sessions, while MB skill utilization was measured by asking participants to indicate at 12 and 24 weeks postpartum the extent to which they used 12 core MB skills taught during the intervention. Age and racial concordance between participant and facilitator were significantly associated with intervention dosage. Those receiving higher intervention dosage tended to be older (27.25 ± 5.96 vs. 24.99 ± 5.60, p < 0.01, OR = 1.068 [1.038-1.098]), and received MB from a facilitator with a self-identified race similar to their own (58% vs. 48%, p = 0.04, OR = 1.485 [1.014-2.176]). Primary language of participants was marginally associated with dosage. Participants receiving a higher dose of intervention tended to exhibit greater MB skill utilization, on average at 24 weeks postpartum. These results can be used to identify strategies to promote intervention engagement. They further suggest that greater intervention dosage leads to increased use of core intervention skills that can promote improvements in participants' behaviors and thoughts.


Cell-associated pentosidine as a marker of aging in human diploid cells in vitro and in vivo.
Cellular aging is characterized by alterations at both the morphological and molecular levels, some of which are decreased mitotic rate, increased cytoplasmic vacuolization, and changes in intrinsic cellular constituents (Stanulis-Praeger, 1987. Mech. Ageing Dev. 38, 1-48). In the present investigation, glycoxidation is studied as a marker for cellular aging by measuring cell-associated pentosidine levels in human skin fibroblasts as a function of replicative life span and in human peripheral blood T lymphocytes as a function of chronological age. Fibroblasts were isolated from culture by detachment/centrifugation while lymphocytes were isolated from blood by a Ficoll-Paque/Lympho-Kwik T-Cell Prep technique. Pentosidine levels were measured in acid-hydrolyzed cell pellet suspensions by high-pressure liquid chromatography. Results show that pentosidine was detected in early and late cultured reticular and papillary fibroblasts. Pentosidine, expressed as either protein, DNA, or cell number, significantly (P < 0.0006) increased with in vitro passage and was significantly (P < 0.01) related to cell proliferation as measured by cell density and cell doublings per day during culture. Cell-associated pentosidine was measured in T lymphocytes isolated from healthy, diabetic, and uremic individuals. In healthy controls, levels significantly (P < 0.0003) increased with age. In uremic individuals, a large variation was observed with many values above the 95% confidence intervals determined for controls. Since a previous study showed that plasma pentosidine in healthy subjects does not increase with age, these results suggest that cellular turnover perhaps coupled to a deterioration in cellular anti-glycoxidation defensive mechanisms play a substantial role in explaining increased pentosidine concentrations during cellular aging.


Mutagenicity of nitropyrenes for Escherichia coli: requirement for increased cellular permeability.
Nitropyrenes are mutagenic to E. coli strains that have increased permeabilities to large molecules and carry plasmid pKM101.


Occupational exposure to nanomaterials and biomarkers in exhaled air and urine: Insights from the NanoExplore international cohort.
The current evidence on nanomaterial toxicity is mostly derived from experimental studies making it challenging to translate it into human health risks. We established an international cohort (N = 141 workers) within the EU-LIFE project "NanoExplore" to address possible health effects from occupational exposures to nanomaterials. We used a handheld direct-reading optical particle counter to measure airborne nanoparticle number concentrations (PNC) and lung-deposited surface areas (LDSAs). Airborne particles were characterized by TEM and SEM-EDAX. We assessed oxidative/nitrosative stress with a panel of biomarkers in exhaled breath condensate (EBC) (8-isoprostane, malondialdehyde, nitrotyrosine), inflammation (high-sensitivity C reactive protein (hs-CRP), IL-1β, TNF-α, IL-10) and KL-6 (considered as biomarker of interstitial lung fibrosis) and urine (total antioxidant power (TAP), 8-isoprostane, and malondialdehyde). Exhaled breath sampled in gas-sampling bags were assessed for oxidative potential. These biomarkers were quantified pre-shift at the beginning of the workweek and post-shift the 4th day. Relationships between airborne nanoparticle concentration and biomarkers were assessed by multiple linear regression with log-transformed exposure and biomarker concentrations adjusted for potential confounders. We found a positive dose-response relationship for three inflammation biomarkers (IL-10, IL-1β and TNF-α) in EBC with both PNC and LDSA. A negative dose-response relationship was observed between PNC and TAP. This study suggests that occupational exposures to nanoparticles can affect the oxidative balance and the innate immunity in occupationally exposed workers. However, owing to the intrinsic variability of biomarkers, the observed changes along with their health significance should be assessed in a long-term perspective study.


Antihypertensive effect of sweetie fruit in patients with stage I hypertension.
Interventional studies have shown that increased intake of fruit and vegetables reduces blood pressure (BP). However, the contribution of specific dietary components has not been evaluated. The aim of the present study was to determine, in patients with stage I hypertension, the antihypertensive effect of juice of the so-called sweetie fruit (a hybrid between grapefruit and pummelo) with and without high flavonoid content. A double-blind, cross-over study was conducted in 12 patients. Each patient received alternately high-flavonoid (HF) sweetie juice and low-flavonoid (LF) sweetie juice, each for a 5-week period. The LF sweetie juice had 25% of naringin and 30% of narirutin content compared with the original HF sweetie juice. The HF sweetie juice was more effective than LF sweetie juice in reducing diastolic blood pressure (P = .04). Systolic blood pressure declined in both groups; however there was no significant difference between subjects given HF sweetie versus those given LF sweetie juice. In this study HF sweetie juice was shown to have a significant beneficial effect in reducing diastolic blood pressure, compared with the effect observed with LF sweetie juice, in patients with stage I hypertension. These data suggest that the active ingredients associated with the antihypertensive effect of sweetie juice are the flavonoids naringin and narirutin.


Proteome changes in the myocardium of experimental chronic diabetes and hypertension: role of PPARα in the associated hypertrophy.
Diabetes with or without the presence of hypertension damages the heart. However, there is currently a lack of information about these associated pathologies and the alteration of linked proteins. For these reasons, we were interested in the potential synergistic interaction of diabetes and hypertension in the heart, focusing on the proteome characterization of the pathological phenotypes and the associated hypertrophic response. We treated normotensive and spontaneously hypertensive (SHR) rats with either streptozotocin or vehicle. After 22weeks, type-I diabetic (DM1), SHR, SHR/DM1 and control left-ventricles were studied using proteomic approaches. Proteomics revealed that long-term DM1, SHR and SHR/DM1 rats exhibited 24, 53 and 53 altered proteins in the myocardia, respectively. DM1 myocardium showed over-expression of apoptotic and cytoskeleton proteins, and down-regulation of anti-apoptotic and mitochondrial metabolic enzymes. In both SHR and SHR/DM1 these changes were exacerbated and free fatty-acid (FFA) ß-oxidation enzymes were additionally decreased. Furthermore, SHR/DM1 hearts exhibited a misbalance of specific pro-hypertrophic, anti-apoptotic and mitochondrial ATP-carrier factors, which could cause additional damage. Differential proteins were validated and then clustered into different biological pathways using bioinformatics. These studies suggested the implication of FFA-nuclear receptors and hypertrophic factors in these pathologies. Although key ß-oxidation enzymes were not stimulated in DM1 and hypertensive hearts, peroxisome proliferator-activated receptors-α (PPARα) were potentially activated for other responses. In this regard, PPARα stimulation reduced hypertrophy and pro-hypertrophic factors such as annexin-V in high-glucose and angiotensin-II induced cardiomyocytes. Thus, activation of PPARα could reflect a compensatory response to the metabolic-shifted, apoptotic and hypertrophic status of the hypertensive-diabetic cardiomyopathy.


A Novel Scoring System for Diagnosing Acute Mesenteric Ischemia in the Emergency Ward.
Early diagnosis of acute mesenteric ischemia (AMI) based on clinical judgment has been proved to be too difficult. Therefore, it is important for identifying clinical parameters that can differentiate AMI from other acute abdomen upon presentation. We analyzed a database of 106 consecutive patients admitted to the emergency ward for suspected AMI in whom diagnosis of AMI was confirmed by laparotomy, CT angiography or mesenteric angiography. The patients' demographics, previous history, clinical signs, results of laboratory investigations and ultrasonography were collected. Diagnostic cutoff value of quantitative indexes was derived from the receiver operating curve. Multivariate logistic regression was used to identify risk factors for AMI and formulated these risk factors into a scoring system. A total of 45 patients (42.5%) were confirmed to have AMI. Compared with other acute abdomen, AMI had significantly increased level of white blood cell (Odds ratio (OR) 16.11, 95% confidence interval (CI) 1.10-235.34), red cell distribution width (OR 27.65, 95% CI 1.53-501.02), mean platelet volume (OR 16.06, 95% CI 1.48-174.50) and D-dimer (OR 42.91, 95% CI 2.56-718.09). A diagnostic score was calculated by adding points assigned to the four parameters, and a cutoff score of four best identified patients with AMI, with sensitivity, specificity, positive and negative predictive values of 97.8, 91.8, 89.8 and 98.2%, respectively. This scoring system based on easily available parameters could be used as a useful tool for differentiating AMI from other acute abdomen in the emergency ward. Prospective studies with large sample remain needed for validating the results.


Updated results and patterns of failure in a randomized hypofractionation trial for high-risk prostate cancer.
To report long-term results and patterns of failure after conventional and hypofractionated radiation therapy in high-risk prostate cancer. This randomized phase III trial compared conventional fractionation (80 Gy at 2 Gy per fraction in 8 weeks) vs hypofractionation (62 Gy at 3.1 Gy per fraction in 5 weeks) in combination with 9-month androgen deprivation therapy in 168 patients with high-risk prostate cancer. Freedom from biochemical failure (FFBF), freedom from local failure (FFLF), and freedom from distant failure (FFDF) were analyzed. In a median follow-up of 70 months, biochemical failure (BF) occurred in 35 of the 168 patients (21%) in the study. Among these 35 patients, local failure (LF) only was detected in 11 (31%), distant failure (DF) only in 16 (46%), and both LF and DF in 6 (17%). In 2 patients (6%) BF has not yet been clinically detected. The risk reduction by hypofractionation was significant in BF (10.3%) but not in LF and DF. We found that hypofractionation, with respect to conventional fractionation, determined only an insignificant increase in the actuarial FFBF but no difference in FFLF and FFDF, when considering the entire group of patients. However, an increase in the 5-year rates in all 3 endpoints-FFBF, FFLF, and FFDF-was observed in the subgroup of patients with a pretreatment prostate-specific antigen (iPSA) level of 20 ng/mL or less. On multivariate analysis, the type of fractionation, iPSA level, Gleason score of 4+3 or higher, and T stage of 2c or higher have been confirmed as independent prognostic factors for BF. High iPSA levels and Gleason score of 4+3 or higher were also significantly associated with an increased risk of DF, whereas T stage of 2c or higher was the only independent variable for LF. Our results confirm the isoeffectiveness of the 2 fractionation schedules used in this study, although a benefit in favor of hypofractionation cannot be excluded in the subgroup of patients with an iPSA level of 20 ng/mL or less. The α/β ratio might be more appropriately evaluated by FFLF than FFBF results, at least in high-risk disease.


Identification of RB1CC1, a novel human gene that can induce RB1 in various human cells.
Multidrug resistance to anti-cancer agents (MDR) is a major barrier to successful cancer treatment. Current knowledge about genes that contribute to MDR is limited, however, and its mechanisms remain unclear. To identify genes involved in MDR, we performed differential display analysis and isolated a novel human gene, RB1CC1 (RBI-inducible Coiled-Coil 1). The 6.6-kb RB1CC1 cDNA encodes a putative 1594-amino-acid protein that contains a nuclear localization signal, a leucine zipper motif and a coiled-coil structure. Western blot analysis and immunocytochemical staining with anti-RB1CC1 antibody showed that endogenously expressed RB1CC1 protein localized to the nucleus. In MDR variants of human osteosarcoma cells, RB1CC1 expression increased in response to doxorubicin-induced cytotoxic stress and remained elevated for the duration of drug treatment. RB1CC1 expression levels correlated closely with those of RB1 (retinoblastoma 1) in cancer cell lines as well as in various normal human tissues. Moreover, introduction of wild-type RB1CC1 significantly induced RB1 expression in human leukemic cells. These data suggest that RB1CC1 may be a key regulator of RB1 gene expression.


Chromatographic quantitation of territrems A, B, and C, tremorgenic mycotoxins from Aspergillus terreus.
This paper describes assay procedures for territrems A, B, and C by thin layer chromatography (TLC)-fluorodensitometry and reverse phase high performance liquid chromatography (HPLC).


Effect of aqueous acetic, oxalic, and carbonic acids on the adsorption of europium(III) onto alpha-alumina.
Chemical retention, i.e., partition of the element between aqueous solution and mineral surface, is a key phenomenon for assessing the safety of possible nuclear waste disposal. For this purpose, the sorption of Eu(III) onto a model mineral-alpha-alumina-is studied here, including the effects of groundwater chemistry: pH and concentrations of small organic and inorganic ligands (acetate, oxalate, and carbonate anions). This work presents some experimental evidence for a synergic mechanism of sorption of europium-ligand complexes onto the alumina. Only cationic complexes were necessary to consider to model experimental results. Using the ion-exchange theory (IET) and a corresponding restricted set of parameters-exchange capacities and thermodynamic equilibrium constants-the whole set of sorption experiments of Eu(III) cationic species onto the alpha-alumina was modeled under various chemical conditions.


Radioprotection of minipig salivary glands by orciprenaline-carbachol. An ultrastructural and semiquantitative light microscopic study.
Parotid and submandibular glands of miniature pigs were exposed to 36 Gy X-irradiation given as 6 x 6 Gy in 3 weeks. Half of the animals received orciprenaline and carbachol before each dose. The effects were analysed 6 months later by light and electron microscopy. Ultrastructural examination showed less change in the pretreated glands. Semi-quantitative light microscopic data confirmed the significance of the differences. Acinar cells of both glands were significantly more numerous (P less than 0.01) and the cells were better preserved (P less than 0.01) in the pretreated group. The effect was more pronounced in the parotid gland, which appeared almost normal. Intercalated ducts of the parotid glands (P less than 0.01) and striated ducts of the submandibular glands (P less than 0.05) showed less change in pretreated animals. The findings confirm the radioprotective effect of pharmacologically induced degranulation of acinar cells. The biological effects of the radiation schedule (cumulative radiation effect value 18.76) as well as the dosage of orciprenaline and carbachol are within the normal range of medical treatment. Similar results may be expected from future studies in man.


Breathing pattern during exercise in untrained children.
Breathing pattern during exercise on a cycle ergometer was studied in 18 untrained children aged from 6 to 15 years of age (9 boys, 9 girls). Oxygen uptake, tidal volume, minute ventilation, all normalized for body weight (VO2BW, VT BW, VE BW), respiratory frequency (f), inspiratory (TI) and expiratory (TE) times, ratio TI over total duration of the respiratory cycle (TI/TTOT) and mean inspiratory flow (VT BW/TI) were measured: (1) at rest (W0) and at the highest load (maximal cardiac rate) of an incremental exercise (W1); (2) in steady state conditions, at 50% of W1 (W1/2) and at 2/3 of W1 (W2/3). VO2BW, VT BW, VE BW, TI/TTOT, VT BW/TI increased significantly (P less than 0.01) from W0 to W1. Behaviour of f and TI were different from the latter parameters: f increased and TI decreased significantly from W0 to W1/2 (P less than 0.01) and from W1/2 to W2/3 (P less than 0.01) but remained similar at W2/3 and W1. We observed a relationship between VO2 BW and VT BW/TI, and between VT BW and TI/TTOT at each step of workload. We conclude that untrained children adapt the pattern of breathing during exercise, as at rest, to metabolic demand. However, the increase in f and the decrease in TI are limited at maximal workload.


Early transcriptomic host response signatures in the serum of dengue patients provides insights into clinical pathogenesis and disease severity.
Dengue virus (DENV), known to cause viral infection, belongs to the family Flaviviridae, having four serotypes (DENV1-4) that spreads by the bite of the Aedes aegypti mosquito. India has been suffering from dengue outbreaks annually with widespread epidemics by prevalence of all the four DENV serotypes. The diverse spectrum of clinical manifestations in dengue infection, mild to severe forms, makes the need of timely diagnosis and prompt treatment an essence. The identification of a dengue host response signature in serum can increase the understanding of dengue pathogenesis since most dengue NS1 Ag tests have been developed and evaluated in serum samples. Here, to understand the same, we undertook a dual RNA-sequencing (RNA-Seq) based approach from the serum samples of dengue-infected patients. The results thus yield the early transcriptional signatures that discriminated the high viral reads patients from patients who had low dengue viral reads. We identified a significant upregulation of two sets of genes, key antiviral (IFIT3, RSAD2, SAT1) and vascular dysfunction (TNFS10, CXCL8) related genes in the high viral reads group. Deeper delving of this gene profile revealed a unique two-way response, where the antiviral genes can mediate the disease course to mild, contrarily the increased expression of the other gene set might act as pointers of severe disease course. Further, we explored the hematologic parameters from the complete blood count (CBC), which suggests that lymphocytes (low) and neutrophils (high) might serve as an early predictor of prognosis in dengue infection. Collectively, our findings give insights into the foundation for further investigation of the early host response using the RNA isolated from dengue patients' serum samples and opens the door for careful monitoring of the early clinical and transcriptome profiles for management of the dengue patients.


Looking for opportunities to co-enroll: The DISCOVERY study experience.
Conducting high-quality stroke trials is complex and costly. Often these trials compete for the attention of researchers and the availability of patients. Enrolling patients in more than one study concurrently has the potential to accelerate recruitment into individual studies. DISCOVERY is a multicenter, inception cohort study of cognitive impairment and dementia following ischemic or hemorrhagic stroke. At the request of site investigators, a DISCOVERY committee reviews individual studies for approval of possible concurrent co-enrollment into DISCOVERY. The purpose of this report is to summarize the characteristics and outcomes of studies reviewed by committee for possible co-enrollment. This analysis covers studies reviewed from 07/01/2020 to 04/26/2022 by the Site Management Committee (SMC) of the DISCOVERY Recruitment and Retention Core. Characterization of each study included study type, number and length of follow-up visits, and whether there were protocol-required blood draws, brain imaging studies, or cognitive tests. Studies were scored for patient burden and scientific overlap with Discovery. The primary outcome was SMC approval to co-enroll. 59 studies were reviewed, and 69.5% (n = 41, 21 clinical trials; 20 observational studies) were found by the SMC to be appropriate for co-enrollment. Higher patient burden and greater scientific overlap with DISCOVERY reduced the rates of approval for co-enrollment. A large number of diverse stroke studies are being run concurrently across the DISCOVERY study network, however, about two-thirds of the studies were considered appropriate for consideration of co-enrollment. Future studies should study how co-enrollment might improve trial network efficiency.


Comparative study on the digestion and absorption characteristics of n-3 LCPUFA-enriched phospholipids in the form of liposomes and emulsions.
Previous studies have reported that phospholipids rich in n-3 long-chain polyunsaturated fatty acids (n-3 LCPUFA) in the form of liposome exhibited superior bioactivities than other formulation. However, the digestion and absorption characteristics of n-3 LCPUFA-enriched phospholipids were still unclear, restricting the molecular mechanism analysis related to their distinctive activities. The aim of the present study was to compare the digestion and absorption characteristics of DHA/EPA-PC in the forms of liposome and emulsion. The fatty acid composition and lipid species in serum, intestinal wall and content of healthy mice were determined after oral administration with DHA/EPA-PC. Results showed that the peak value of serum DHA/EPA level in the liposome group was significantly higher than that of the emulsion group (p < 0.05), although the peak in the liposome group appeared at 3 h and the peak time was 2 h in the emulsion group. Lipidomics analysis indicated that the high levels of total PL and PL-DHA could be retained in serum for a substantial period after administration of the DHA/EPA-PC liposome, which might be attributed to that the DHA/EPA-PC in the form of liposomes was hydrolyzed slower by pancreatic phospholipase A2 than the emulsion form in small intestinal content. The obtained results might provide theoretical basis for the development and utilization of marine-derived phospholipids.


Immunoglobulin light-chain genes in the rhesus macaque II: lambda light-chain germline sequences for subgroups IGLV1, IGLV2, IGLV3, IGLV4 and IGLV5.
The combined processes of immunoglobulin (IG) gene rearrangement and somatic hypermutation allow for the creation of an extremely diverse antibody repertoire. Knowledge of the germline sequence of the IG genes is required so that hypermutation and the affinity matured humoral response can be properly studied. Variable region genes can be arranged into subgroups; in humans, there are 11 IGLV subgroups and 6 IGKV subgroups. The rhesus macaque (Macaca mulatta) is a relevant non-human primate model for human immunological systems. A number of macaque IGHV, IGHD and IGHJ genes have already been reported. We have also previously reported a number of macaque IGKV genes. Here we report the isolation of new macaque IGLV genes by polymerase chain reaction amplification from macaque genomic DNA using primers based on the human sequences. Nine IGLV1, 10 IGLV2, 21 IGLV3, 5 IGLV4 and 7 IGLV5 germline genes for the macaque were found, the open-reading frames of which exhibit high homology to their human counterparts (>89.3, >88.6, >89.0, >94.7 and >87.1%, respectively).


No Differences in Outcomes in People with Low Back Pain Who Met the Clinical Prediction Rule for Lumbar Spine Manipulation When a Pragmatic Non-thrust Manipulation Was Used as the Comparator.
To investigate differences in pain and disability between patients treated with thrust manipulation (TM) and those treated with non-thrust manipulation (NTM) in a group of patients with mechanical low back pain (LBP) who had a within-session response to an initial assessment and met the clinical prediction rule (CPR). Data from 71 patients who met the CPR were extracted from a database of patients in a larger randomized controlled trial comparing TM and NTM. Treatment of the first two visits involved either TM or NTM (depending on allocation) and a standardized home exercise programme. Data analysis included descriptive statistics and a two-way ANOVA examining within- and between-groups effects for pain and disability, as well as total visits, total days in care, and rate of recovery. No between-group differences in pain or disability were found for NTM versus TM groups (p=0.55), but within-subjects effects were noted for both groups (p<0.001). This secondary analysis suggests that patients who satisfy the CPR benefit as much from NTM as from TM.


[Immunohematological study of 7 cases of acquired B transformation using anti-B and selected acquired anti-B].
Seven acquired B samples were studied with selected anti-B sera. Eight sera came from group A subjects, four from group O subjects. The anti-B sera reacting with the acquired B antigen are always a mixture of two kinds of antibodies: a fraction that is only reactive with B antigen, another that is cross-reactive with B and acquired B antigens. In some sera, especially those coming from group O subjects, there is, in addition, a potent antibody of polyagglutination for acquired B red cells. The polyagglutinability associated with acquired B red cells is analysed. According to the results obtained using lectins, four red cell samples are merely acquired B, the three others are acquired B + Tk. The polyagglutinability associated with Tk transformation is non sensitive to acetylation of red cells. The polyagglutinability specific for acquired B is sensitive to acetylation but appears complex in itself. According to the reactivity of selected sera for acquired B samples and the studies of inhibition with simple sugars, there are at least two antigens involved. One of them is present in all of the acquired B samples and it is likely to have arisen from the action of a deacetylase on a structure including N-acetylgalactosamine.


Proceedings of the 2020 Epilepsy Foundation Pipeline Conference: Emerging Drugs and Devices.
From August 27-28, 2020 the Epilepsy Foundation hosted the Pipeline Conference, exploring emerging issues related to antiepileptic drug and device development. The conference featured epilepsy therapeutic companies and academic laboratories developing drugs for focal epilepsies, innovations for rare and ultra-rare diseases, and devices both in clinical trials and approved for use. In this paper, we outline the virtual presentations by the authors, including novel data from their development pipeline.


Sucrose metabolism gene families and their biological functions.
Sucrose, as the main product of photosynthesis, plays crucial roles in plant development. Although studies on general metabolism pathway were well documented, less information is available on the genome-wide identification of these genes, their expansion and evolutionary history as well as their biological functions. We focused on four sucrose metabolism related gene families including sucrose synthase, sucrose phosphate synthase, sucrose phosphate phosphatase and UDP-glucose pyrophosphorylase. These gene families exhibited different expansion and evolutionary history as their host genomes experienced differentiated rates of the whole genome duplication, tandem and segmental duplication, or mobile element mediated gene gain and loss. They were evolutionarily conserved under purifying selection among species and expression divergence played important roles for gene survival after expansion. However, we have detected recent positive selection during intra-species divergence. Overexpression of 15 sorghum genes in Arabidopsis revealed their roles in biomass accumulation, flowering time control, seed germination and response to high salinity and sugar stresses. Our studies uncovered the molecular mechanisms of gene expansion and evolution and also provided new insight into the role of positive selection in intra-species divergence. Overexpression data revealed novel biological functions of these genes in flowering time control and seed germination under normal and stress conditions.


A comparative genomics study on the effect of individual amino acids on ribosome stalling.
During protein synthesis, the nascent peptide chain emerges from the ribosome through the ribosomal exit tunnel. Biochemical interactions between the nascent peptide and the tunnel may stall the ribosome movement and thus affect the expression level of the protein being synthesized. Earlier studies focused on one model organism (S. cerevisiae), have suggested that certain amino acid sequences may be responsible for ribosome stalling; however, the stalling effect at the individual amino acid level across many organisms has not yet been quantified. By analyzing multiple ribosome profiling datasets from different organisms (including prokaryotes and eukaryotes), we report for the first time the organism-specific amino acids that significantly lead to ribosome stalling. We show that the identity of the stalling amino acids vary across the tree of life. In agreement with previous studies, we observed a remarkable stalling signal of proline and arginine in S. cerevisiae. In addition, our analysis supports the conjecture that the stalling effect of positively charged amino acids is not universal and that in certain conditions, negative charge may also induce ribosome stalling. Finally, we show that the beginning part of the tunnel tends to undergo more interactions with the translated amino acids than other positions along the tunnel. The reported results support the conjecture that the ribosomal exit tunnel interacts with various amino acids and that the nature of these interactions varies among different organisms. Our findings should contribute towards better understanding of transcript and proteomic evolution and translation elongation regulation.


Chlorine oxide radical (ClO) enables the enhanced degradation of antibiotic resistance genes during UV/chlorine treatment by selectively inducing base damage.
Compared to individual UV or chlorine disinfection, the combined UV and chlorine (i.e., UV/chlorine) can substantially promote the degradation of antibiotic resistance genes (ARGs) in the effluent by generating radicals. However, the mechanisms of ARG degradation induced by radicals during UV/chlorine treatment remain largely unknown, limiting further enhancement of ARG degradation by process optimization. Herein, we aimed to uncover the role of different radicals in ARG degradation and the molecular mechanisms of ARG degradation by radicals in UV/chlorine process. The ClO was proven to be responsible for the enhanced ARG degradation during UV/chlorine treatment, while the other radicals (OH, Cl, and Cl2-) played a minor role. This is because ClO possessed both high steady-state concentration and high reactivity toward ARGs (rate constant: 4.29 × 1010 M-1 s-1). The ClO might collaborate with free chlorine to degrade ARG. The ClO degraded ARGs by selectively attacking guanine and thymine but failed to induce strand breakage, while chlorine could break the strand of ARGs. Ultimately, ClO cooperated with chlorine to degrade ARGs quickly by hydroxylation and chlorination of bases and produce many chlorine- and nitrogen-containing products as revealed by high-resolution mass spectrometry. The uncovered degradation mechanisms of ARGs by UV/chlorine provide useful guidelines for process optimization to achieve deep removal of effluent ARGs.


Comparative chemical, biological and clinical studies of 99mtc-glucoheptonate and 99mtc-dimercaptosuccinate as used in renal scintigraphy.
The renal radiopharmaceutical preparations 99mTc-DMS and 99mTc-GH were examined chemically, biologically and clinically. Both preparations are of high radiochemical purity. The biodistribution of both preparations was examined in experimental animals at different time intervals, from 15 min to 4 hr; the precentage of incorporation of 99mTc-DMS into kindeys is much higher (29.4% to 52.0%) than that of 99mTc-GH (12.80% to 22.20%). Both preparations accumulate to a greater extent in the renal cortex than in the medulla. The most suitable time for renal scintigraphy for 99mTc-DMS is 90--150 min while for 99mTc-GH it is 60--90 min. It is concluded that 99mTc-DMS is more suitable for static scintigrams on the scanner and 99mTc-GH for dynamic studies with the gamma camera.


Computer Tomography Angiography of Peripheral Vascular Injuries.
Peripheral vascular injuries are a rare finding in the setting of trauma but an important source of morbidity and mortality when present. Fast and accurate diagnosis followed by rapid repair of vascular injuries are important for achieving the best clinical outcomes. The advancements in computer tomography (CT) and decades of experience in vascular imaging have allowed radiologists to become important contributors for the diagnosis and characterization of peripheral vascular injury. We review the epidemiology of peripheral vascular injuries, indications for imaging, ways to optimize CT technique, imaging findings, and common challenges for accurate diagnosis of such injuries.


Apnea and Diffuse Alveolar Hemorrhage Caused by Cocaine and Heroin Use: A Case Report.
Drug overdose represents a growing reason for emergency department visits and hospitalizations in the United States. Co-ingestion of multiple substances is also on the rise, and toxidromes can be seen from any of multiple drugs in a single patient. We present a case of diffuse alveolar hemorrhage secondary to cocaine abuse in a patient who was apneic and unresponsive after heroin overdose. The patient responded to supportive care and was discharged with complete return to physical and mental baseline. Clinicians must be vigilant for any number of concomitant toxidromes when a patient is brought in with complications following drug overdose.


RNA polymerase interactions with the upstream region of the E. coli tyrT promoter.
The rate of in vivo transcription from the E. coli tRNA and rRNA promoters depends on both cellular growth rate and aminoacid availability. To investigate the molecular mechanisms involved we determined the extent of interaction of RNA polymerase with the promoter of the tyrT stable RNA gene. We show that the enzyme can protect from DNAase I digestion a region of at least 85 bp of the wild-type tyrT promoter and only approximately 62 bp of the lacUV5 mRNA promoter, the protected region extending on the antisense strand to approximately 65 and 42 bp respectively upstream of the transcription startpoint. A mutant tyrT promoter, tyrTp27, is protected more extensively, RNA polymerase interactions extending to at least approximately -130. We propose that these upstream interactions of RNA polymerase perform two functions; activating initiation by polymerase bound at the primary binding site and increasing the concentration of polymerase in the vicinity of the tyrT promoter, thus allowing a high rate of maximal expression and enabling the promoter to be regulated over a wide range of activity.


[Training in patient safety in medical and nursing schools].
To compare the information on patient safety received by students of medicine and nursing. Cross-sectional study was conducted using a convenience sample of medical and nursing students of 3 Universities. The Latin Patient Safety Student Information and a test of 5 questions with 5 options were used. A sample of 79 students in each group was enrolled to detect differences of .3 units (bilateral estimation), considering 80% statistical power and 95% confidence interval. A total of 144 students replied (74 nursing and 70 medicine students). Nursing students achieved higher scores in the communication with patients factor (3.8 vs 3.2, P<.001) and proactive attitude to identify risks for patient safety (4.3 vs 3.8, P<.001). Medical students were more aware of the inevitability of adverse events (2.3 vs 3.1, P<.001). Ten (7%) students had only one fault in the test, and only one (1%) answered all questions correctly. The training in patient safety should be improved both in nursing and medicine, although nursing students receive more information.


Ethanol-induced taste aversions: lack of involvement of acetaldehyde and the area postrema.
Two experiments were run to evaluate the role of acetaldehyde and the area postrema in the acquisition of an ethanol-induced conditioned taste aversion. An ethanol-induced taste aversion was observed in male Sprague-Dawley rats with a dose of 4 g/kg. PO, but not after doses of 1 or 2 g/kg. Pretreatment with 4-methylpyrazole (8 mg/kg, IP), which itself did not induce an aversion as compared to pyrazole (68 mg/kg, IP) that did, and/or prior application of lesions of the area postrema had no influence on the development of an ethanol-induced taste aversion. The results indicate that ethanol-induced taste aversion learning does not result from the metabolism of ethanol to acetaldehyde and does not, like other toxins, involve the mediation of the area postrema.


Active treatment of patients with "incurable disease": what's the point?
What is active treatment of patients with "incurable disease"? I believe that it is not limited to the care of the patients' symptoms, but goes further. We can and must control pain, breathlessness, nausea and vomiting, intestinal obstruction, insomnia… but something else remains for us to face, something paradoxically made more evident by the absence of symptoms: the patients' emotional suffering, suffering deep in their heart, the most hidden, but which becomes apparent in the season of death. So, what can we do? We must be able to understand their needs and to stay with them, protecting the uniqueness of their person in the face of an imminent death.


Integrating remote monitoring into heart failure patients' care regimen: A pilot study.
Around 50% of hospital readmissions due to heart failure are preventable, with lack of adherence to prescribed self-care as a driving factor. Remote tracking and reminders issued by mobile health devices could help to promote self-care, which could potentially reduce these readmissions. We sought to investigate two factors: (1) feasibility of enrolling heart failure patients in a remote monitoring regimen that uses wireless sensors and patient-reported outcome measures; and (2) their adherence to using the study devices and completing patient-reported outcome measures. Twenty heart failure patients participated in piloting a remote monitoring regimen. Data collection included: (1) physical activity using wrist-worn activity trackers; (2) body weight using bathroom scales; (3) medication adherence using smart pill bottles; and (4) patient -reported outcomes using patient-reported outcome measures. We evaluated 150 hospitalized heart failure patients and enrolled 20 individuals. Two factors contributed to 50% (65/130) being excluded from the study: smartphone ownership and patient discharge. Over the course of the study, 60.0% of the subjects wore the activity tracker for at least 70% of the hours, and 45.0% used the scale for more than 70% of the days. The pill bottle was used less than 10% of the days by 55.0% of the subjects. Our method of recruiting heart failure patients prior to hospital discharge may not be feasible as the enrollment rate was low. Once enrolled, the majority of subjects maintained a high adherence to wearing the activity tracker but low adherence to using the pill bottle and completing the follow-up surveys. Scale usage was fair, but it received positive reviews from most subjects. Given the observed usage and feedback, we suggest mobile health-driven interventions consider including an activity tracker and bathroom scale. We also recommend administering a shorter survey more regularly and through an easier interface.


Implementing a Locally Made Low-Cost Intervention for Wound and Lymphedema Care in Western Kenya.
In Western Kenya, the burden of chronic wounds and lymphedema has a significant impact on functionality and quality of life. Major barriers to provision of care include availability, affordability, and accessibility of bandages. At the Academic Model Providing Access to Healthcare, dermatologists and pharmacists collaborated to develop a 2-component compression bandage modeled after the Unna boot, using locally available materials, that is distributed through a revolving fund pharmacy network. In partnership with nursing, use of these bandages at a national referral hospital and a few county facilities has increased, but increasing utilization to an expanded catchment area is needed.


Magnetic resonance investigation of blood flow after aortic valve bypass (apicoaortic conduit).
Aortic valve bypass (AVB, apicoaortic conduit) is an alternative to aortic valve replacement (AVR) for high-risk patients with aortic stenosis (AS). The redistribution of blood flow after AVB has been poorly characterized. In order to understand cardiovascular physiology after AVB, we performed cardiac magnetic resonance (CMR) imaging of AVB recipients. Fifteen patients with symptomatic AS underwent beating-heart AVB. Electrocardiography-gated two-dimensional phase-contrast velocity mapping CMR imaging was conducted on each patient. Instantaneous flow was acquired at discrete intervals within the cardiac cycle and ventricular function and volumes were evaluated. Five age-matched patients without aortic valve disease served as controls. Conduit flow (as a percent of total cardiac output) was 65% ± 5%. Ejection fraction was unchanged compared with before AVB (50% ± 17% versus 57% ± 13%; p = 0.91). Ventricular volumes and cardiac indices were within normal limits and similar to those values in controls (cardiac index 2.9 ± 1.0 versus 2.3 L/min/m(2); p = 0.26; end-diastolic volume index 59 ± 17 mL versus 55 ± 20 mL; p = 0.66; end-systolic volume index, 25 ± 12 versus 25 ± 18 mL; p = 0.91; stroke volume index, 33 ± 11 versus 30 ± 6 mL; p = 0.57 for AVB and control patients, respectively). There was a small degree of retrograde blood flow in the descending aorta above the level of the conduit insertion (10% ± 8% of cardiac output). Aortic valve bypass results in a predictable blood flow distribution between the native aorta and conduit and is associated with normal ventricular volumes and function.


Dendritic spine loss in the hippocampus of young PDAPP and Tg2576 mice and its prevention by the ApoE2 genotype.
Postmortem AD brains exhibit dendritic spine loss in the hippocampus. To determine whether this pathology may be associated with amyloid burden, the present study used the Golgi stain technique to assess age- and genotype-dependent changes in dendritic spine density in CA1 hippocampus of two transgenic mouse lines that produce high levels of Abeta. Tg2576 and PDAPP mice, as well as a group of Tg2576 mice crossed with human apoE2-expressing transgenic mice, were compared to respective transgene-negative controls. Since the time course of amyloid plaque deposition in the PDAPP and Tg2576 mice is well characterized, we examined changes in spine density at ages that corresponded to different levels of amyloid plaque load. The data show age- and genotype-dependent reductions in spine density in both Tg2576 and PDAPP mice, albeit at somewhat different time courses. The spine loss occurred prior to plaque deposition and was ameliorated by the overexpression of human apoE2. These results suggest that a soluble Abeta species may affect hippocampal synapses and thereby contribute to functional deficits evident in these animals.


Bidisperse Magnetic Particles Coated with Gelatin and Graphite Oxide: Magnetorheology, Dispersion Stability, and the Nanoparticle-Enhancing Effect.
The magnetorheology and dispersion stability of bidisperse magnetic particles (BMP)-based magnetorheological (MR) fluids were improved by applying a novel functional coating composed of gelatin and graphite oxide (GO) to the surfaces of the micron-sized carbonyl iron (CI) and nanoparticles Fe₃O₄. Gelatin acted as a grafting agent to reduce the aggregation and sedimentation of CI particles and prevent nanoparticles Fe₃O₄ from oxidation. In addition, a dense GO network on the surface of gelatin-coated BMP was synthesized by self-assembly to possess a better MR performance and redispersibility. The rheological properties of MR fluids containing dual-coated BMP were measured by a rotational rheometer under the presence of magnetic field and their dispersion stability was examined through sedimentation tests. The results showed that CI@Fe₃O₄@Gelatin@GO (CI@Fe₃O₄@G@GO) particles possessed enhanced MR properties and dispersion stability. In addition, the nanoparticle-enhancing effects on the dispersion stability of BMP-based MR fluids were investigated using Monte Carlo simulations.


Dyserythropoiesis and myelodysplasia in thiamine-responsive megaloblastic anemia syndrome.
The case of thiamine-responsive megaloblastic anemia (TRMA) presented here speculates the need early diagnosis, continuous monitoring, follow-up, and regulated treatment plan for the patients. Complications and systemic manifestations are likely to enhance in otherwise circumstances.


A Case of Mycobacterial Skin Disease Caused by Mycobacterium peregrinum, and a Review of Cutaneous Infection.
An 83-year-old Japanese man presented with a 2-month history of symptomatic nodules on the left hand. He was not in an immunocompromised condition and reported no causal events. A biopsy specimen demonstrated granulomatous tissue with mixed cell infiltration consisting of neutrophils, histiocytes, lymphocytes, and multinuclear giant cells. No bacillus was detected by PAS, acid-fast stain, immunofluorescent stain or polymerase chain reaction analysis. The isolate was found to be a rapidly growing mycobacterium after 4 weeks of incubation at 25°C on an Ogawa egg slant. Mycobacterium peregrinum was isolated by DNA-DNA hybridization analysis, 16S rRNA gene sequence, and by its production of 3-day arylsulfatase. The patient received 200 mg oral minocycline for 28 weeks. The lesion disappeared after 10 weeks of this treatment.


Comparison of Apolipoprotein B/A1 ratio, Framingham risk score and TC/HDL-c for predicting clinical outcomes in patients undergoing percutaneous coronary intervention.
Apolipoproteins (Apo) are known atherogenic factors that play important roles in many mechanisms related to coronary heart disease (CHD). However, it is unclear whether the apoB/apoA1 ratio is an equal or a better predictor than the Framingham Risk Score or TC/HDL-c for predicting clinical outcomes in patients undergoing percutaneous coronary intervention. We investigated the association between Apolipoprotein B/A1 ratio and cardiovascular risk factors as well as the severity of CHD in 2256 Han Chinese patients. The potential of Apolipoprotein B/A1 ratio, Framingham Risk Score and TC/HDL-c were assessed as a marker to predict cardiovascular adverse events in a prospective subgroup of 1639 CHD patients during a 5-year follow-up. In the multivariate model, adjusted odds ratios (ORs) were significant for 3-VD vs. 1-VD (OR = 2.36; 95% CI: 1.65-3.38, for the fourth vs. first quartile; Ptrend < 0.001). The subgroup analysis showed that patients with a higher ApoB/ApoA1 ratio had an increased risk of developing multi-branch lesions and potentially suffer more cardiovascular adverse events (anginas, myocardial infarctions, heart failures, strokes, and cardiac deaths) in the future (adjusted HR =1.92; 95% CI: 1.10-3.13, for the fourth vs. first quartile). In the ROC analysis, the AUC for ApoB/A1 ratio was larger than that of Framingham Risk Score (0.604 vs. 0.543, p = 0.01) and TC/HDL-c (0.604 vs. 0.525, p < 0.01). Our results suggest a significant association between ApoB/ApoA1 ratio and CHD severity and cardiovascular outcomes among patients with existing CHD and ApoB/A1 ratio demonstrated a better predictive accuracy for clinical outcomes compared with Framingham Risk Score and TC/HDL-c.


[The journey of the Guarayos to the land of the dead. A transcultural psychiatric study].
The investigation of the being of a culture has the power of revealing something about the existence of the human beings that form it. The ethnographic study of the Guarayos, in which we find the great 'mythologem' of the agricultural people, allows us to understand the collective and permanent drunkenness that characterizes it.


Studies of introital colonization in women with recurrent urinary infections. III. Vaginal glycogen concentrations.
The concentration of glycogen in vaginal fluid was measured in 37 samples from 6 volunteers without urinary infections and in 96 samples from 12 patients with recurrent urinary infections. The mean glycogen concentrations, 440 mug. per ml. from the controls and 564 mug. per ml. from the patients, were not statistically different (p more than 0.05). Although an introital pH more than or equal to 4.4 was associated with low concentrations of glycogen in vaginal fluid, a pH less than 4.4 was found with high and low glycogen concentration. Sodium concentration was statistically higher in vaginal fluid from patients compared to controls (p less than 0.01) while potassium concentration was the same in both groups.


Medium nitrogen optimized Boehmeria nivea L. growth in copper contaminated soil.
Copper (Cu) pollution in agricultural soils is considered as a serious health risk due to its accumulation in plants. Thus, there is an urgent need to optimize nutrient application for higher yield with lower Cu uptake to ensure food security. A pot experiment was conducted to investigate the effectiveness of nitrogen fertilizer (N) on Boehmeria nivea growth, gas exchange characteristics, antioxidant capacity and uptake of Cu in contaminated soil. Therefore, combinations of Cu levels (0, 100, 300 mg kg-1) and N levels (0, 140, 280, 420 kg ha-1) were applied. The results showed that N at 280 kg ha-1 significantly (≤0.05) increased plant growth in terms of fresh biomass, plant height, stem diameter and number of leaves per plant up to100 mg kg-1 Cu in soil for all harvests (H1, H2, H3 and H4). However, the interactive effect of Cu and N on Cu uptake by plant varied among N levels. Furthermore, N at 280 kg ha-1 also improved the gas exchange characteristics viz., net photosynthesis (Pn), transpiration rate (Tr) and stomatal conductance (gs), while decreased oxidative stress in B. nivea up to 100 mg kg-1 Cu in soil, relative to control. Thus N at 280 kg ha-1 can be considered as an effective dose for high fresh biomass with lower Cu uptake by B. nivea grown as fodder in Cu contaminated soils (≤100 mg kg-1). Overall, present research highlighted the necessity of balanced or optimum N application for sustainable B. nivea forage production in Cu contaminated agricultural lands.


Inhibition of thermolysin with nitrone-bearing substrate analogs: a new type of thermolysin inhibitors.
Nitrones are utilized as the active site zinc coordinating functionality in the design of inhibitors for thermolysin. This new type of thermolysin inhibitors are as potent as the existing inhibitors bearing a carboxylate or hydroxamate zinc ligating moiety.


Ru(phen)3(2+) doped silica nanoparticle based immunochromatographic strip for rapid quantitative detection of β-agonist residues in swine urine.
A Ru(phen)3(2+) doped silica nanoparticle based immunochromatographic strip was developed for the rapid and quantitative detection of five common β-agonist (salbutamol (SAL), cimbuterol, terbutaline, clenbuterol, and brombuterol) residues in swine urine. The broad spectrum monoclonal antibodies generated by immunizing BALB/c mice with salbutamol conjugated cationic bovine serum albumin. The fluorescence intensities (FIs) of the strip on the test line (FIT) and control line (FIC) were determined using a strip reader. Parameters that influenced the antibody and antigen interaction on the test strip were investigated by recording FIT and FIC values, and the concept of FIT/FIC ratio was used to offset the inherent heterogeneity of the test strips and the effect of the sample matrix. Under optimal conditions, the linear range for the quantitative detection of SAL was 0.6-5.0 ng/ml with a half maximal inhibitory concentration at 1.78 ng/ml. The limit of detection for real swine urine was 0.43 ng/ml. The recovery rates of the intraassay for spiked urine at SAL concentrations of 0.8, 1.5, and 3.5 ng/mL were 88.06%±3.75%, 95.77%±5.33%, and 94.06%±7.43%, whereas those for the interassay were 84.69%±5.0%, 95.06%±9.3%, and 88.34%±7.71%, respectively. The developed quantitative method exhibited excellent agreement with a commercially available competitive enzyme-linked immunosorbent assay kit for SAL-spiked urine samples, with a correlation of coefficient of 0.95 and a slope of 0.99 (n=36). The results indicated that the developed test strip enables sensitive, reproducible, and easily implementable screening for the rapid and quantitative detection of β-agonist residues in swine urine.


First detection of Cryptosporidium proventriculi from wild birds in Cyprus.
Cryptosporidium is an important intestinal zoonotic pathogen that can infect various hosts and cause diarrheal disease. There are no reports on the prevalence and molecular characterization of Cryptosporidium in wild birds in Cyprus. Therefore, the present study aimed to determine the prevalence of Cryptosporidium spp. and genotypes in wild birds found at Phassouri Reedbeds (Akrotiri Wetlands), Cyprus. Fecal samples of 75 wild birds (Eurasian coot Fulica atra, N = 48; Eurasian teal Anas crecca, N = 20; duck - Anas spp., Ν = 7) were screened for Cryptosporidium by PCR amplification and sequencing. Only one sample (1.3%) belonging to a Eurasian coot was PCR-positive for Cryptosporidium. Based on sequencing of the 18S rRNA locus, this species was identified as Cryptosporidium proventriculi. This is the first report on the molecular identification of this Cryptosporidium species in a Eurasian coot.


History of suicidal behaviour in the families of young suicides.
The prevalence of attempted or completed suicide was studied in the families of a consecutive sample of young suicide victims aged 15-29 years. In 17 of 42 (40%) of the men and 5 of 16 (31%) of the women suicidal behaviour was found to be present in first-degree relatives. Male suicide victims with a family history of suicidal behaviour had an earlier debut of their own suicidal behaviour, longer suicidal processes, and had made more previous suicide attempts. Families in which suicidal behaviour was displayed by the victim's parents or siblings also had more frequent early separations between parent and victim and more substance abuse. Taking into account suicide by a friend or second-degree family member, it was found that 72% of suicide victims had a history of suicidal behaviour in close relationships.


[Intraductal biliary metastases from colorectal cancer: a report of two cases].
Intrabiliary metastases are rare, and their imaging characteristics make them easy to confuse with primary biliary tumors, especially with cholangiocarcinoma. We present two cases of patients with histories of colorectal cancer who presented with obstructive jaundice secondary to intraductal metastases. We describe the imaging findings and emphasize the key radiologic manifestations for the differential diagnosis between intrabiliary metastases and primary biliary tumors.


Reconstructive algorithm and classification system for transoral oropharyngeal defects.
Transoral techniques for oropharyngeal tumors, such as transoral robotic surgery (TORS) and transoral laser microsurgery, require new reconstructive considerations. Defects from 92 patients undergoing TORS were classified into 4 classes. A reconstruction algorithm was followed. Perioperative outcomes and complications were assessed. Forty-seven patients completed the MD Anderson Dysphagia Inventory (MDADI) swallowing questionnaire and a modified Velopharyngeal Insufficiency Quality of Life (VPIQL) questionnaire postoperatively. The most common reconstructions involved velopharyngoplasties with local flaps (39%), local flaps alone (25%), or secondary healing (20%). More advanced defects (class III and IV defects) required regional and free flaps more often. No significant differences were found in MDADI scores or VPIQL scores among the 4 defect classes. Only adjuvant radiotherapy was a predictor of poor swallowing (p = .02). The classification system for transoral oropharyngeal defects maps defects into 4 classes and guides the reconstructive thought process.


European eels and heavy metals from the Mar Menor lagoon (SE Spain).
Heavy metal pollution is related to the fall in European eel (Anguilla anguilla) populations. The Mar Menor lagoon (SE Spain) is home to an endangered population of this species, which is still caught for human consumption. The presence of Pb, Cd and Hg in the livers and muscles and the Se:Hg ratio in muscle of 150 eels from this lagoon were determined. Pb concentrations were higher than those reported from other populations in the world, while Cd and Hg concentrations in the tissues analysed were lower. In terms of food safety, Se concentrations play an important role in sequestering Hg in eels from this lagoon.


A multivariate model for predicting mortality in patients with heart failure and systolic dysfunction.
Heart failure is a leading cause of morbidity and mortality, but there are no reliable models based on readily available clinical variables to predict outcomes in patients taking angiotensin-converting enzyme (ACE) inhibitors. A multivariate statistical model to predict mortality was developed in a random sample (n = 4277 patients [67%]) of the 6422 patients enrolled in the Digitalis Investigation Group trial who had a depressed ejection fraction (<or=45%), were in sinus rhythm, and were taking ACE inhibitors. The model was then validated in the remaining 2145 patients. Total mortality in the derivation sample was 11.2% (n = 480) at 12 months and 29.9% (n = 1277) at 36 months. Lower ejection fraction, worse renal function, cardiomegaly, worse functional class, signs or symptoms of heart failure, lower blood pressure, and lower body mass index were associated with reduced 12-month survival. This model provided good predictions of mortality in the verification sample. The same variables, along with age and the baseline use of nitrates, were also predictive of 36-month mortality. Routine clinical variables can be used to predict short- and long-term mortality in patients with heart failure and systolic dysfunction who are treated with ACE inhibitors.


Microwave: practical cost-effective method for sterilizing urinary catheters in the home.
We used a standard microwave oven to sterilize red rubber catheters used for intermittent self-catheterization. Catheters were incubated for sixty minutes in a suspension of microorganisms isolated from the urine of patients with urinary tract infections. For each trial, 6 catheters were removed from their respective suspensions, placed in separate plastic freezer bags, distributed evenly in a microwave oven (avoiding cold spots), and microwaved simultaneously for twelve minutes. A control catheter was not microwaved. Two strains of each microorganism were tested. The urinary isolates were Escherichia coli, Klebsiella sp., Proteus sp., Enterobacter sp., Pseudomonas sp., Streptococcus sp., Staphylococcus sp., and Candida sp. In each experiment, all 6 catheters were sterilized. Repeat sterilization in the microwave oven did not affect the integrity of the catheters or the plastic bags. A water heat sink of constant volume was employed. A home microwave oven may be used as a method to sterilize red rubber catheters for reuse with a recommended time of twelve minutes at full power. This technique makes aseptic intermittent self-catheterization a practical possibility.


[Expression and distribution of cysteinyl leukotriene receptors CysLT1R and CysLT2R, and GPR17 in brain of Parkinson disease model mice].
To examine the spatiotemporal profiles and localization of CysLT1R, CysLT2R and GPR17 in mice with 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced Parkinson disease (PD). PD model was induced by subcutaneous injection of MPTP (25 mg/kg) for 5 d in adult male C57BL/6 mice. At d10 after MPTP injection, the expression and cellular localization of CysLT1R, CysLT2R and GPR17 in the substantia nigra were detected by immunohistochemistry and immunofluorescence. CysLT1R, CysLT22 and GPR17 were normally localized in TH-positive dopaminergic neurons and microglia, while CysLT2R was also expressed in astrocytes. In dopaminergic neurons, approximately 91% co-expressed GPR17, 77% co-expressed CysLT1R and 52% co-expressed CysLT2R. Compared with the control group, TH-positive cells in the substantia nigra were significantly reduced in PD mice. CysLT1R, CysLT2R and GPR17-positive cells were significantly reduced; and CysLT1R, CysLT2R, GPR17-positive dopaminergic neurons were also significantly reduced in the PD group. In the striatum, both CysLT1R and GPR17 were normally expressed in neurons; whereas CysLT2R was expressed in astrocytes. In PD striatum, CysLT1R and GPR17-positive cells were decreased, but CysLT2R expression was significantly increased which mainly expressed in the proliferating astrocytes. CysLT1R, CysLT2R and GPR17 may be involved in the MPTP-induced PD damage in mice.


Phloridzin reduces blood glucose levels and alters hepatic gene expression in normal BALB/c mice.
We previously showed that a diet containing phloridzin suppressed the blood glucose levels in streptozotocin-induced diabetic mice most likely by inhibiting glucose absorption from the small intestine. In this study, we showed that 0.5% and 1% phloridzin diets significantly reduce the blood glucose levels in healthy normal BALB/c mice after 7 days of feeding. The 0.1% phloridzin diet did not suppress blood glucose levels but induced the alteration of the hepatic gene expressions related to carbohydrate and fatty acid metabolism in mice after 14 days. Ingenuity Pathway Analysis showed that 0.5% and 1% phloridzin diets suppressed the hepatic gene expressions related to the citrate cycle, gluconeogenesis, fatty acid metabolism, and valine, leucine, and isoleucine degradation in mice when compared with mice fed a control diet after 14 days. Thus the diet containing phloridzin reduces the blood glucose levels and the hepatic gene expressions associated with some metabolic functions in mice.


[Neurologic complications in the immediate postoperative period after cardiac surgery. Role of brain magnetic resonance imaging].
Neurologic complications still cause significant morbidity and mortality in the immediate postoperative period following cardiac surgery. Our understanding of the pathogenesis, prevention, and management of these lesions is constantly developing. We describe neurologic complications and their course in a cardiac surgery cohort and analyze the value of brain magnetic resonance imaging (MRI), using T1-weighted, T2-weighted, and FLAIR sequences, in patients with postoperative stroke or encephalopathy in whom CT scanning revealed no abnormalities explaining their clinical condition. In 688 patients studied postoperatively, we observed 57 neurologic complications (8.3%): 25 strokes, 24 encephalopathies, 5 seizure disorders, 2 brain deaths, and 1 intracranial hemorrhage. Initial CT scanning failed to show significant findings in 70%. 18 patients underwent brain MRI. In all but 1 of the 11 with stroke, MRI showed areas of acute or subacute infarction (i.e., hyperintensity in FLAIR or T2-weighted sequences) in different locations, mainly in a watershed distribution. In 3 of the 4 patients with mild-to-moderate encephalopathy, MRI showed lesions similar to those previously described for stroke. In the remaining 3 patients, who had severe encephalopathy, MRI showed diffuse cortical necrosis. The incidence of neurologic complications in the postoperative period following cardiac surgery is significant. In a high percentage of patients, brain CT scanning may not show pathologic findings. In selected patients, MRI could help identify areas of infarction not detected by CT. These images could improve clinicians' understanding of the pathogenic, pathophysiologic, clinical, and prognostic characteristics of such neurologic complications.


Development and psychometric analysis of a new tool to assess food literacy in diabetic patients.
One of the factors affecting self-care in diabetic patients is food literacy, which helps said patients in following a healthy diet. Thus, it is crucial to analyze food literacy in diabetic patients through suitable and reliable instruments. OBJECTIVE: The current study aimed to design a questionnaire for food literacy assessment in diabetic patients and analyze its psychometric features. The present study was a cross-sectional descriptive analysis carried out in 2021. Firstly, the concepts of food literacy in diabetic patients were identified and the questionnaire was deigned based on them. Secondly, its face and content validities and its reliability were analyzed. Finally, the construct validity was analyzed by exploratory factor analysis. The study was carried out on 300 diabetic participants chosen at random via stratified cluster sampling from Health service centers. The exploratory factor analysis was carried out by extracting the main factors and using varimax rotation with eigenvalue values more than 1. A five-pronged structure accounted for 52.745% of food literacy variance. This included the ability to read food facts, practical ability to group foods, the ability to identify the caloric content of different foods, the ability to understand the effect of food on health, and the ability to prepare a healthy meal. Items with an impact score below 1.5 were discarded. Additionally, items with CVR scores below 0.62 and CVI scores below 0.79 were deleted too. The Kaiser-Meyer-Okin measurement was 0.836 (p < 0.001). Alpha Cronbach Scale dimension was 0.610-0.951. The results of this study showed that the exploratory dimensions of the current study were consistent with health literacy measurements, such as functional, interactive, and critical food literacy. This scale has acceptable reliability and validity. Health professionals can use this scale to analyze and improve food literacy in diabetic patients. This is a new instrument and thus far no questionnaire has been made to evaluate food literacy in diabetic patients.


Partial lateral corpectomy for ventral extradural thoracic spinal cord compression in a cat.
A 7-year-old, female spayed, domestic shorthair cat was presented for ambulatory paraparesis. No trauma history was reported. Myelography and subsequent computed tomography revealed multiple ventrally located extradural spinal cord compressive lesions possibly due to intervertebral disc disease. Compression at the level of Th3-Th4 intervertebral disc space was considered responsible for the paraparesis. The lesion was approached via a right-sided lateral partial corpectomy as described for dogs. Complete spinal decompression was achieved, as documented intraoperatively by visual inspection and palpation of the spinal canal. No surgery related complications were encountered and the cat improved gradually within 8 weeks after the procedure. At 1 year follow-up only a slight proprioceptive deficit in the right hind limb could be noted. This is the first report of partial lateral corpectomy in a cat and should encourage the use of this technique even in small patients.


Predictive factors for postoperative constipation and continence after stapled transanal rectal resection.
Although stapled transanal rectal resection (STARR) has become an important surgical option in the treatment of obstructive defaecation syndrome, objective data about parameters that predict its success or failure are not yet available. Medical history, clinical and radiomorphological data were obtained prospectively from a multi-institutional STARR registry. Predictive factors for postoperative constipation (Cleveland Clinic Constipation Score, CCS) and incontinence (Cleveland Clinic Incontinence Score, CCIS) were identified using univariable and multivariable analysis. Data were obtained for 181 of 201 patients in the STARR registry, with completed median follow-up of 19·4 (range 12-41) months. Although the CCS decreased significantly overall (from mean(s.d.) 16·3(4·9) to 6·7(4·1); P < 0·001), 31 patients (17·1 per cent) complained about persisting constipation. CCIS levels remained unchanged overall, but 16 patients (8·8 per cent) had new-onset faecal incontinence. Multivariable analysis revealed that rectocele (β = -0·302, P < 0·001) and intussusception (β = -0·392, P < 0·001) were independent predictors of low CCS levels, and intussusception (β = -0·216, P = 0·001) and enterocele (β = -0·171, P = 0·012) were independent predictors of low CCIS levels. In contrast, small rectal diameter (β = -0·293, P < 0·001), low squeeze pressure (β = -0·188, P = 0·005) and increased pelvic floor descent at rest (β = 0·264, P < 0·001) predicted high CCIS levels. Factors for a favourable outcome after STARR included rectocele, intussusception and enterocele, whereas small rectal diameter, low sphincter pressure and increased pelvic floor descent were unfavourable. These findings should be integrated into the therapy algorithm for STARR.


Prediction of neonatal hypoglycemia in infants of diabetic mothers by glucose disappearance in the first hour of life.
Whole blood glucose determinations were obtained in the first hour of life in 44 infants of diabetic mothers in order to predict the occurrence of subsequent hypoglycemia by means of the calculated glucose disappearance rate. Hypoglycemia (whole blood glucose less than 20 mg/dl) occurred in 10 infants with linear glucose disappearance of whom 9 had a glucose disappearance rate greater than or equal to 3.0% per min (90% sensitivity). Nine of 11 infants with glucose disappearance rates greater than or equal to 3.0% per min had hypoglycemia (82% specificity). This relatively simple procedure offers an accurate method for prediction of neonatal hypoglycemia due to reactive hyperinsulinemia in infants of diabetic mothers.


The Impact of Antepartum Depression and Postpartum Depression on Exclusive Breastfeeding: A Systematic Review and Meta-Analysis.
The aim of this study was to systematically review the impact of antepartum depression on exclusive breastfeeding. A total of 15 studies were included in the review and 12 studies were used for the meta-analysis. The mean values of antepartum depression indicated that women who breastfed exclusively between 3 and 6 months had less antepartum depression symptoms (Mean Difference = -0.55, 95% CI = -0.76 to -0.35). The analysis also showed that the existence of antepartum depression was negatively related to continuing exclusive breastfeeding for longer than 3 months postpartum as well as for 8 weeks postpartum (OR = 0.48, 95% CI = 0.26-0.88 and OR = 0.83, 95% CI = 0.75-0.91, respectively). The cumulative evidence is conclusive that antepartum depressive symptoms are negatively associated with exclusive breastfeeding, particularly between 3 and 6 months postpartum. This review supports the necessity of screening and follow-up for depression throughout the perinatal period to promote exclusive breastfeeding for 6 months.


Engineering Vibrio fischeri transcriptional activator LuxR for diverse transcriptional activities.
To alter DNA binding specificity of Vibrio fischeri LuxR and to expand the toolbox for constructing synthetic networks. A mutation library (about 10,000 individuals) of the DNA binding domain of LuxR were generated. A genetic selection was performed to obtain LuxR mutants that recognize three lux box DNA variants that are not recognized by wild-type LuxR. Six LuxR mutants were identified. The evolved LuxR mutants were further characterized by measuring the transcriptional activities of different combinations of LuxR mutants and lux box variants. Varied transcriptional activities were found in these LuxR-lux box pairs. The background expressions of the evolved LuxR-lux box systems are more tightly regulated than the wild-type LuxR-lux box system. The LuxR transcriptional system was evolved to recognize three lux box DNAs which are not recognized by wild-type LuxR.


Therapeutic Hypothermia for Refractory Hypoxemia on Venovenous Extracorporeal Membrane Oxygenation: An In Silico Study.
Patients with respiratory failure may remain hypoxemic despite treatment with venovenous extracorporeal membrane oxygenation (VV-ECMO). Therapeutic hypothermia is a potential treatment for such hypoxia as it reduces cardiac output ( ) and oxygen consumption. We modified a previously published mathematical model of gas exchange to investigate the effects of hypothermia during VV-ECMO. Partial pressures were expressed as measured at 37°C (α-stat). The effect of hypothermia on gas exchange was examined in four clinical scenarios of hypoxemia on VV-ECMO, each with different physiological derangements. All scenarios had arterial partial pressure of oxygen (PaO 2 ) ≤ 46 mm Hg and arterial oxygen saturation of hemoglobin (SaO 2 ) ≤ 81%. Three had high with low extracorporeal blood flow to ratio ( ). The problem in the fourth scenario was recirculation, with normal . Cooling to 33°C increased SaO 2 to > 89% and PaO 2 to > 50 mm Hg in all scenarios. Mixed venous oxygen saturation of hemoglobin as % ( ) increased to > 70% and mixed venous partial pressure of oxygen in mm Hg ( ) increased to > 34 mm Hg in scenarios with low . In the scenario with high recirculation, and increased, but to < 50% and < 27 mm Hg, respectively. This in silico study predicted cooling to 33°C will improve oxygenation in refractory hypoxemia on VV-ECMO, but the improvement will be less when the problem is recirculation.


[Pericardial window by videothorascopy].
Pericardial effusion is a clinical condition requiring multidisciplinary management. There are several surgical techniques for its diagnosis and treatment. In the present study we report our experience in performing a pericardial window (PW) by videothorascopy. We performed surgery on 56 patients (20 females and 36 males), with a mean age of 56±1.22 years, and diagnosed with moderate to severe chronic pericardial effusion. The side chosen for the approach depended on whether there was an associated pleural effusion or lung lesion, and if not the left side was chosen. The mean duration of the surgery was 37.6±16 minutes. The definitive diagnoses were malignant processes in 23% of cases, including bronchogenic carcinoma and breast cancer. The intra-operative mortality was 0%. Videothorascopic pericardial window is an effective and safe technique for the diagnosis and treatment of chronic pericardial effusion, and which enables it to be drained and perform a pleuro-pulmonary and/or mediastinal biopsy during the same surgical act.


Zinc-induced copper deficiency.
Copper deficiency was found in an adult patient who had received excessive daily oral zinc for 10 mo. The deficiency was characterized by hypochromic-microcytic anemia, leukopenia, and neutropenia. Although initially thought to be caused by iron deficiency, the anemia did not respond to oral or intravenous iron. Cessation of zinc tablets and ingestion of an oral copper preparation daily for 2 mo failed to correct the anemia or leukopenia. It was not until shortly after intravenous administration of a cupric chloride solution during a 5-day period, at a total dose of 10 mg, that serum copper and ceruloplasmin levels increased and the anemia, leukopenia, and neutropenia resolved. These data suggest that the elimination of excess zinc is slow and that, until such elimination occurs, the intestinal absorption of copper is blocked.


NBT-test in asthmatic patients with regard to bacterial infections and steroid therapy.
In this communication we report our negative experience in differentiating bacterially infected from non-infected adult asthmatic patients, using a simplified modification of the NBT-test. The outcome of the test was unrelated to the steroid dose of the patient.


Impact of imatinib on the pharmacokinetics and in vivo efficacy of etoposide and/or ifosfamide.
Using a human small cell lung cancer (SCLC) xenografted in nude mice, we have previously reported enhanced tumor growth inhibition following chemotherapy in combination with imatinib (STI571). We therefore investigated the in vivo impact of imatinib on the pharmacokinetics and efficacy of chemotherapy. Two different human tumors were used: SCLC6 small cell lung cancer xenografted in nude mice, and LY-3 EBV-associated human B-cell lymphoma xenografted in SCID mice. Plasma, urine, and fecal concentrations of etoposide (VP16) were determined by a validated high performance liquid chromatography method. Plasma concentrations of ifosfamidewere determined by a validated gas chromatography assay with nitrogen-phosphorus detection. Slight tumor growth inhibition was induced by imatinib administered alone in one in vivo EBV-associated B-cell lymphomatous xenograft. In contrast, an increase of the chemotherapy-induced antitumor effect was observed in the lymphoma model but not in a small cell lung cancer model when mice bearing human xenografted tumors were treated concomitantly by imatinib and chemotherapy. This antitumor effect was not influenced by concomitant administration of fluconazole. The AUC0-3 h (Area Under the concentration-time Curve) of etoposide was increased when mice were treated with etoposide + imatinib due to decreased fecal excretion. In contrast, imatinib did not appear to influence the urinary excretion of etoposide, and concomitant administration of the CYP3A4 inhibitor, fluconazole, with imatinib did not modify the pharmacokinetics of etoposide plus imatinib alone. Altogether, these results therefore justify further prospective phase I and II clinical trials with combinations of etoposide-based chemotherapy and imatinib in patients with certain cancers, such as malignant lymphoma, with careful toxicologic monitoring.


A hexokinase with broad sugar specificity from a thermophilic bacterium.
A recombinant thermophilic Thermus caldophilus GK24 hexokinase, one of the ROK-type (repressor protein, open reading frames, and sugar kinase) proteins, exists uniquely as a 120 kDa molecule with four subunits (31 kDa), in contrast to eukaryotic and bacterial sugar kinases which are monomers or dimers. The optimal temperature and pH for the enzyme reaction are 70-80 degrees C and 7.5, respectively. This enzyme shows broad specificity toward glucose, mannose, glucosamine, allose, 2-deoxyglucose, and fructose. To understand the sugar specificity at a structural level, the enzyme-ATP/Mg2+-sugar binding complex models have been constructed. It has been shown that the sugar specificity is probably dependent on the interaction energy occurred by the positional proximity of sugars bound in the active site of the enzyme, which exhibits a tolerance to modification at C2 or C3 of glucose.


Transcriptional cofactor TBLR1 controls lipid mobilization in white adipose tissue.
Lipid mobilization (lipolysis) in white adipose tissue (WAT) critically controls lipid turnover and adiposity in humans. While the acute regulation of lipolysis has been studied in detail, the transcriptional determinants of WAT lipolytic activity remain still largely unexplored. Here we show that the genetic inactivation of transcriptional cofactor transducin beta-like-related 1(TBLR1) blunts the lipolytic response of white adipocytes through the impairment of cAMP-dependent signal transduction. Indeed, mice lacking TBLR1 in adipocytes are defective in fasting-induced lipid mobilization and, when placed on a high-fat-diet, show aggravated adiposity, glucose intolerance, and insulin resistance. TBLR1 levels are found to increase under lipolytic conditions in WAT of both human patients and mice, correlating with serum free fatty acids (FFAs). As a critical regulator of WAT cAMP signaling and lipid mobilization, proper activity of TBLR1 in adipocytes might thus represent a critical molecular checkpoint for the prevention of metabolic dysfunction in subjects with obesity-related disorders.


Multivalent bicyclic peptides are an effective antiviral modality that can potently inhibit SARS-CoV-2.
COVID-19 has stimulated the rapid development of new antibody and small molecule therapeutics to inhibit SARS-CoV-2 infection. Here we describe a third antiviral modality that combines the drug-like advantages of both. Bicycles are entropically constrained peptides stabilized by a central chemical scaffold into a bi-cyclic structure. Rapid screening of diverse bacteriophage libraries against SARS-CoV-2 Spike yielded unique Bicycle binders across the entire protein. Exploiting Bicycles' inherent chemical combinability, we converted early micromolar hits into nanomolar viral inhibitors through simple multimerization. We also show how combining Bicycles against different epitopes into a single biparatopic agent allows Spike from diverse variants of concern (VoC) to be targeted (Alpha, Beta, Delta and Omicron). Finally, we demonstrate in both male hACE2-transgenic mice and Syrian golden hamsters that both multimerized and biparatopic Bicycles reduce viraemia and prevent host inflammation. These results introduce Bicycles as a potential antiviral modality to tackle new and rapidly evolving viruses.


[Measurement of the pressure, flow and viscosity behavior of liver bile].
The physical and dynamic condition of the liver-gall was examined. Flow-condition as the basis for intraoperational gallducts, already applied method of operation, was analysed. Our results show, the dynamic condition of liver-gall included in the law of Hagen-Poisseuille in the gall-flowing, do not have structured-viscosity and that the liver-gall is approximately identical to the Newton-fluid. A new method of examining the intraoperative flow and pressure measurement is suggested.


Resveratrol inhibits ovarian tumor growth in an in vivo mouse model.
Resveratrol inhibits the growth of ovarian carcinoma cells in vitro through the inhibition of glucose metabolism and the induction of both autophagy and apoptosis. In the current study, we investigated the metabolic and therapeutic effects of resveratrol in vivo. A fluorescent xenograft mouse model of ovarian cancer was used. Mice were treated with cisplatin, resveratrol, or vehicle alone. Tumor burden was assessed using whole-body imaging. The effect of resveratrol on glucose uptake in vivo was determined using micro-positron emission tomography scanning. To determine whether resveratrol could inhibit tumor regrowth, tumor-bearing mice were treated with cisplatin followed by either daily resveratrol or vehicle. Autophagic response in resected tumors taken from mice treated with resveratrol was examined by transmission electron microscopy. Glycolysis and mitochondrial respiration in ovarian tumor cells after treatment with resveratrol was assessed. Mice treated with resveratrol and cisplatin were found to have a significantly reduced tumor burden compared with control animals (P<.001). Resveratrol-treated mice demonstrated a marked decrease in tumor uptake of glucose compared with controls. After treatment with cisplatin, "maintenance" resveratrol resulted in the suppression of tumor regrowth compared with mice receiving vehicle alone (P<.01). Tumors resected from mice treated with resveratrol exhibited autophagosomes consistent with the induction of autophagy. Treatment with resveratrol inhibited glycolytic response in ovarian tumor cells with high baseline glycolytic rates. Treatment with resveratrol inhibits glucose uptake and has a significant antineoplastic effect in a preclinical mouse model of ovarian cancer. Resveratrol treatment suppresses tumor regrowth after therapy with cisplatin, suggesting that this agent has the potential to prolong disease-free survival. Cancer 2016;122:722-729. © 2015 American Cancer Society.


Development and validation of a prediction model for unsuccessful treatment outcomes in patients with multi-drug resistance tuberculosis.
The World Health Organization has reported that the treatment success rate of multi-drug resistance tuberculosis is approximately 57% globally. Although new drugs such as bedaquiline and linezolid is likely improve the treatment outcome, there are other factors associated with unsuccessful treatment outcome. The factors associated with unsuccessful treatment outcomes have been widely examined, but only a few studies have developed prediction models. We aimed to develop and validate a simple clinical prediction model for unsuccessful treatment outcomes in patients with multi-drug resistance pulmonary tuberculosis (MDR-PTB). This retrospective cohort study was performed between January 2017 and December 2019 at a special hospital in Xi'an, China. A total of 446 patients with MDR-PTB were included. Least absolute shrinkage and selection operator (LASSO) regression and multivariate logistic regression were used to select prognostic factors for unsuccessful treatment outcomes. A nomogram was built based on four prognostic factors. Internal validation and leave-one-out cross-validation was used to assess the model. Of the 446 patients with MDR-PTB, 32.9% (147/446) cases had unsuccessful treatment outcomes, and 67.1% had successful outcomes. After LASSO regression and multivariate logistic analyses, no health education, advanced age, being male, and larger extent lung involvement were identified as prognostic factors. These four prognostic factors were used to build the prediction nomograms. The area under the curve of the model was 0.757 (95%CI 0.711 to 0.804), and the concordance index (C-index) was 0.75. For the bootstrap sampling validation, the corrected C-index was 0.747. In the leave-one-out cross-validation, the C-index was 0.765. The slope of the calibration curve was 0.968, which was approximately 1.0. This indicated that the model was accurate in predicting unsuccessful treatment outcomes. We built a predictive model and established a nomogram for unsuccessful treatment outcomes of multi-drug resistance pulmonary tuberculosis based on baseline characteristics. This predictive model showed good performance and could be used as a tool by clinicians to predict who among their patients will have an unsuccessful treatment outcome.


MHC class II-associated invariant chain contains a sorting signal for endosomal compartments.
The invariant chain (Ii) is a transmembrane protein that associates with the MHC class II molecules in the endoplasmic reticulum. Expression of Ii in MHC class II-negative CV1 cells showed that it acquired complex-type oligosaccharide side chains and was retained in endosomal compartments. To search for a sorting signal, we made progressive deletions from the cytoplasmic N-terminus of Ii. Deleting 11 amino acid residues resulted in a protein that was still sorted and retained in endosomal vesicles, whereas deletion of 15 or more amino acid residues resulted in a protein that became resident in the plasma membrane. Amino acids 12-15 are thus essential for intracellular transport to endosomal compartments. As Ii is intracellularly associated with the MHC class II molecules, it is proposed that Ii determines the intracellular transport route of these molecules.


Causes, clinical features and non-operative management of bile leaks.
This paper evaluates the management of 31 patients with bile leaks identified over a 7-year period. Leaks complicated cholecystectomy in 19 patients (11 laparoscopic, 8 open), interventional procedures in 10 (including surgery in 1), trauma in one and was spontaneous in one case. Confirmation of the diagnosis typically lagged behind the onset of symptoms (mean for the group 4.2 days), indicating that a high index of suspicion is required in at-risk patients with typical symptoms. These include abdominal pain or distension, fever, bile leaking along a drain, jaundice, abnormal liver function tests and elevated white cell count. Two post-surgical bile leaks required surgical drainage of abdominal cellections. The remainder were successfully managed by non-operative methods including percutaneous drainage, endoscopic retrograde cholangiography with or without sphincterotomy or stent placement and percutaneous stenting. The spontaneous leak and all bile leaks complicating interventional procedures were managed non-operatively, although six patients in this group died due to the underlying malignant pathology. Only the patient with self-inflicted transection of the bile duct died directly from the complications of the bile leak. Although this is a varied, small series, we conclude that the majority of bile leaks can be managed by non-operative techniques. Whilst endoscopy is the primary modality for treatment, percutaneous techniques are crucially important for the management of complex cases and endoscopic failure.


[Effect of inhibitor HNP1 transfection on tumor growth of human nasopharyngeal carcinoma cell line HNE-1].
The aim of this study is to investigate the effects of inhibitor HNP1 transfection on proliferation and tumor growth of human nasopharyngeal carcinoma cell line HNE1. HNE1 cells were transfected with HNP1 by liposome, and the cytotoxic effect was detected by MTT, In vivo tumor growth test was performed in nude mice inoculated with transfected HNE1 cells. The therapeutic effect of HNP1 was evaluated in the inoculated tumors, alpha-defensin 1 expression was detected in implanted tumor tissues by immunohistochemical stain. HNP1 transfection significantly inhibited the proliferation of HNE1 cells. MTT assay confirmed cytotoxic effect. In vivo study showed tumor volume was significantly smaller in HNP1 transfection group than that in control group (P < 0.01). Immunohistochemical stain showed alpha-defensin expression was increased in HNP1 transfection group. HNP1 transfection can inhibit the proliferation of HNE1 cells, as well as tumor growth.


The Italian CABG Outcome Study: short-term outcomes in patients with coronary artery bypass graft surgery.
During the last decade, a worldwide growing interest in evaluating performance of health services through 'outcome studies' took place. This study started in early 2002 and represents the first National Health System (NHS) experience to evaluate adjusted performance indicators at national level. The aim of this study was to compare 30 days mortality after coronary artery bypass graft (CABG) between cardiac surgery centres, adjusting by confounding risk factors. All patients, aged 15-99 years, undergoing a CABG intervention after 1st January 2002 in 82 participating centres were eligible for this observational longitudinal study. For each patient, data on severity and risk factors were collected (type of procedure, haemodynamic condition, co-morbidities, recent myocardial infarction and unstable angina, ventricular function, emergency condition, vital status at 30 days). Using a multiple logistic regression analysis the best predictive model was developed for risk-adjustment; a cross-validation procedure was applied; specific risk adjusted mortality rates (RAMR) were estimated. The overall study population was used as reference standard. 34,310 isolated CABG were performed in 64 of the 82 participating centres. Thirty days mortality resulted 2.61%, ranging from 0.33 to 7.63%; eight centres presented a RAMR significantly lower and seven significantly higher than the reference. The study provides valid measures of the heterogeneity between outcomes of the Italian cardiac surgery centres, to support decision-making by NHS management and individual patients. Although not statistically significant, RAMR dropped from year 2002 to 2004 (2.8-2.4%) suggesting that this comparative outcome assessment can contribute to the improvement of performances in cardiac surgery.


Emerging Roles of Adipose Progenitor Cells in Tissue Development, Homeostasis, Expansion and Thermogenesis.
Stem or progenitor cells are an essential component for the development, homeostasis, expansion, and regeneration of many tissues. Within white adipose tissue (WAT) reside vascular-resident adipose progenitor cells (APCs) that can proliferate and differentiate into either white or beige/brite adipocytes, which may control adiposity. Recent studies have begun to show that APCs can be manipulated to control adiposity and counteract 'diabesity'. However, much remains unknown about the identity of APCs and how they may control adiposity in response to homeostatic and external cues. Here, we discuss recent advances in our understanding of adipose progenitors and cover a range of topics, including the stem cell/progenitor lineage, their niche, their developmental and adult roles, and their role in cold-induced beige/brite adipocyte formation.


Pre-COVID-19 international travel and admission to hospital when back home: travel behavior, carriage of highly resistant microorganisms, and risk perception of patients admitted to a large tertiary care hospital.
When people who recently travelled abroad are admitted to a hospital back home, there is a risk of introducing highly resistant microorganisms (HRMO) into the hospital. To minimize this risk, a feasible infection prevention strategy should be developed. In this study, we investigated patients' travel history and behavior during travel and analyzed whether this was correlated to HRMO carriage at admission. From May 2018 until August 2019, adult patients admitted to a large tertiary care center in the Netherlands were asked upon hospital admission to participate in the study. Included patients received a questionnaire about risk perception, travel history in the last year, and behavior during travel, and were screened for HRMO carriage at admission using a perianal swab. Six hundred and eight questionnaires were handed out, of which 247 were returned (40.6%). One hundred and thirty (52.6%) patients did not travel abroad in the last year, of whom eight (6.2%) were HRMO carrier at admission. One hundred seventeen (47.4%) patients travelled in the preceding year, of whom seven patients (6.0%) were HRMO carrier at admission. Thirty patients (12%) travelled outside of Europe; in this group HRMO prevalence was 13.3% (4 out of 30). The majority of patients (71.3%) were aware that international travel could lead to carriage of HRMO, and an even larger majority (89.5%) would support a screening strategy upon hospital admission in case of a travel history, to minimize the risk of introducing HRMO. We identified that half of admitted patients to a large tertiary care hospital travelled abroad in the last year, with only a small percentage outside Europe. We discuss several screening strategies and propose a strategy of screening and preemptive isolation of patients who travelled to Asia or Africa in the 2 months before their hospital admission; a strategy that patients would support.


Degenerative myelopathy associated with a missense mutation in the superoxide dismutase 1 (SOD1) gene progresses to peripheral neuropathy in Pembroke Welsh corgis and boxers.
Canine degenerative myelopathy (DM) is an adult-onset, fatal neurodegenerative disease with many similarities to an upper-motor-neuron-onset form of human amyotrophic lateral sclerosis (ALS), that results from mutations in the superoxide dismutase (SOD1) gene. DM occurs in many dog breeds, including the Pembroke Welsh Corgi and Boxer. The initial upper motor neuron degeneration produces spastic paraparesis and affected dogs develop general proprioceptive ataxia in the pelvic limbs. Dog owners usually elect euthanasia when their dog becomes paraplegic. When euthanasia is delayed, lower motor neuron signs including ascending tetraparesis, flaccid paralysis and widespread muscle atrophy emerge. For this study, muscle and peripheral nerve specimens were evaluated at varying disease stages from DM-affected Pembroke Welsh Corgis and Boxers that were homozygous for the SOD1 mutation and had spinal cord histopathology consistent with DM. Comparisons were made with age- and breed-matched control dogs. Here we provide evidence that Pembroke Welsh Corgis and Boxers with chronic DM develop muscle atrophy consistent with denervation, peripheral nerve pathology consistent with an axonopathy, and to a lesser degree demyelination. Canine DM has been proposed as a potential spontaneous animal disease model of human ALS. The results of this study provide further support that canine DM recapitulates one form of the corresponding human disorder and should serve as a valuable animal model to develop therapeutic strategies.