Enantioselective Guest Effect on the Spin State of a Chiral Coordination Framework.
The diversity of spin crossover (SCO) complexes that, on the one hand, display variable temperature, abruptness and hysteresis of the spin transition, and on the other hand, are spin-sensitive to the various guest molecules, makes these materials unique for the detection of different organic and inorganic compounds. We have developed a homochiral SCO coordination polymer with a spin transition sensitive to the inclusion of the guest 2-butanol, and these solvates with (R)- and (S)-alcohols demonstrate different SCO behaviours depending on the chirality of the organic analyte. A stereoselective response to the guest inclusion is detected as a shift in the temperature of the transition both from dia- to para- and from para- to diamagnetic states in heating and cooling modes respectively. Furthermore, the Mössbauer spectroscopy directly visualizes how the metallic centres in a chiral coordination framework differently sense the interaction with guests of different chiralities.


HSI-II Gene Cluster of Pseudomonas syringae pv. tomato DC3000 Encodes a Functional Type VI Secretion System Required for Interbacterial Competition.
The type VI secretion system (T6SS) is a widespread bacterial nanoweapon used for delivery of toxic proteins into cell targets and contributes to virulence, anti-inflammatory processes, and interbacterial competition. In the model phytopathogenic bacterium Pseudomonas syringae pv. tomato (Pst) DC3000, two T6SS gene clusters, HSI-I and HSI-II, were identified, but their functions remain unclear. We previously reported that hcp2, located in HSI-II, is involved in competition with enterobacteria and yeast. Here, we demonstrated that interbacterial competition of Pst DC3000 against several Gram-negative plant-associated bacteria requires mainly HSI-II activity. By means of a systematic approach using in-frame deletion mutants for each gene in the HSI-II cluster, we identified genes indispensable for Hcp2 expression, Hcp2 secretion and interbacterial competition ability. Deletion of PSPTO_5413 only affected growth in interbacterial competition assays but not Hcp2 secretion, which suggests that PSPTO_5413 might be a putative effector. Moreover, PSPTO_5424, encoding a putative σ54-dependent transcriptional regulator, positively regulated the expression of all three operons in HSI-II. Our discovery that the HSI-II gene cluster gives Pst DC3000 the ability to compete with other plant-associated bacteria could help in understanding a possible mechanism of how phytopathogenic bacteria maintain their ecological niches.


CT Features of Benign Intrapulmonary Lymph Nodes in Pediatric Patients With Known Extrapulmonary Solid Malignancy.
OBJECTIVE. The purpose of our study was to determine the CT features of benign intrapulmonary lymph nodes in pediatric patients with known extrapulmonary solid malignancy. MATERIALS AND METHODS. A retrospective review of surgical pathology archives was performed to identify consecutive chest CT studies of pediatric patients (≤ 18 years) with extrapulmonary solid malignancy and histologically confirmed benign intrapulmonary lymph nodes between January 1, 2004, and March 15, 2020. CT features of intrapulmonary lymph nodes-including size, shape, margin, type, associated calcification or fat, and location-were independently evaluated by two pediatric radiologist reviewers. The CT features of benign intrapulmonary lymph nodes in pediatric patients were analyzed using summary statistics. Interobserver agreement was measured with the kappa coefficient. RESULTS. There were 36 pathology-confirmed benign intrapulmonary lymph nodes in 27 pediatric patients (18 boys and nine girls; mean age, 12 years; age range, 1-18.2 years). Twenty-three (63.9%) of the benign intrapulmonary lymph nodes were biopsied from the right lung and 13 (36.1%) from the left lung (p = .03). The mean size, determined from CT studies, of benign intrapulmonary lymph nodes was 3.6 mm (SD, 1.4 mm; range, 1.3-7.8 mm). Triangular shape (25/36, 69.4%) was the most common shape of the benign intrapulmonary lymph nodes. Less commonly seen shapes of benign intrapulmonary lymph nodes were oval (6/36, 16.7%), round (3/36, 8.3%), and trapezoidal (2/36, 5.6%). All benign intrapulmonary lymph nodes were smoothly marginated and solid without associated calcification or fat. Of the 36 benign intrapulmonary lymph nodes, 15 (41.7%) were pleura-based; 11 (30.6%), perifissural; and 10 (27.8%), parenchymal. The kappa value for interobserver agreement between the two reviewers was 0.917 (95% CI, 0.825-1.000; standard error, 0.047), which corresponds to near-perfect agreement. CONCLUSION. In pediatric patients with known extrapulmonary solid malignancy, benign intrapulmonary lymph nodes are subcentimeter (mean size, 3.6 mm), smoothly marginated, and solid without containing calcification or fat on CT. In particular, triangular shape was the most commonly encountered shape of a benign intrapulmonary lymph node.


Atherosclerotic cardiovascular events associated with immune checkpoint inhibitors in cancer patients.
Immune checkpoint inhibitors have demonstrated significant clinical benefits in many cancers, and the use of these drugs is rapidly expanding. Unfortunately, these agents can induce a wide range of immune-related adverse events through the activation of immune responses in non-target organs, including the cardiovascular system. Among cardiovascular immune-related adverse events, myocarditis is the most established and biologically plausible cardiac complication of immune checkpoint inhibitors therapy with immune-related pathophysiology. In contrast, atherosclerotic cardiovascular diseases, such as myocardial infarction and ischemic stroke, were not previously recognized as a part of the immune-related adverse event spectrum. However, there is now increasing preclinical and clinical evidence that suggests a possible correlation between immune checkpoint inhibitors therapy and atherosclerotic cardiovascular events, and cardiovascular disease is increasingly recognized as a toxicity of ICIs. Results from animal studies suggest that the blockade of the cytotoxic T-lymphocyte antigen 4 or programmed cell death protein 1 pathway plays a relevant role in promoting the progression of atherosclerotic lesions. Several clinical studies have reported an increased incidence of atherosclerotic vascular events after immune checkpoint inhibitor administration. Our findings suggest that clinicians should (i) recognize that immune checkpoint inhibitors can exacerbate atherosclerosis, (ii) consider the management of cardiovascular risk factors and (iii) perform periodic screening in patients receiving immune checkpoint inhibitors.


Manipulation and microrheology of carbon nanotubes with laser-induced cavitation bubbles.
Multiwalled carbon nanotubes (MWCNT) are exposed to a transient and strong liquid jet flow created by a pair of differently sized laser-induced cavitation bubbles. The position and size of the bubbles are controlled with a spatial light modulator within a 15 microm thick liquid gap. Depending on the tube's position with respect to this jet flow, rotation, translation, and a bending deformation is observed with a high-speed camera recording at up to 300,000 frames per second. By measuring the decay time of the respective bending modes we determine the flexural rigidity of MWCNTs to be on the range of 0.45-4.06x10(-19) N m2. The average diameter of the MWCNTs is 117.8+/-6.7 nm with a thickness of 4.6+/-0.75 nm, yielding a Young's modulus between 0.033-0.292 TPa.


Rose WRKY13 promotes disease protection to Botrytis by enhancing cytokinin content and reducing abscisic acid signaling.
The plant hormones cytokinin (CK) and abscisic acid (ABA) play critical and often opposite roles during plant growth, development, and responses to abiotic and biotic stresses. Rose (Rosa sp.) is an economically important ornamental crop sold as cut flowers. Rose petals are extremely susceptible to gray mold disease caused by the necrotrophic fungal pathogen Botrytis cinerea. The infection of rose petals by B. cinerea leads to tissue collapse and rot, causing severe economic losses. In this study, we showed that CK and ABA play opposite roles in the susceptibility of rose to B. cinerea. Treatment with CK enhanced the disease protection of rose petals to B. cinerea, while ABA promoted disease progression. We further demonstrated that rose flowers activate CK-mediated disease protection via a B. cinerea-induced rose transcriptional repressor, Rosa hybrida (Rh)WRKY13, which is an ortholog of Arabidopsis (Arabidopsis thaliana), AtWRKY40. RhWRKY13 binds to promoter regions of the CK degradation gene CKX3 (RhCKX3) and the ABA-response gene ABA insensitive4 (RhABI4), leading to simultaneous inhibition of their expression in rose petals. The increased CK content and reduced ABA responses result in enhanced protection from B. cinerea. Collectively, these data reveal opposite roles for CK and ABA in the susceptibility of rose petals against B. cinerea infection, which is mediated by B. cinerea-induced RhWRKY13 expression.


Protective effect of Tribulus terrestris L. fruit aqueous extracton lipid profile and oxidative stress in isoproterenol induced myocardial necrosis in male albino Wistar rats.
The objective of the present study was to evaluate the possible protective effects of Tribulus terrestris fruit aqueous extract (TTFAEt) on lipid profile and oxidative stress in isoproterenol (ISO) induced myocardial necrosis in albino Wistar rats. Albino Wistar rats were divided into normal control, TTFAEt alone treated, ISO control and pretreated (TTFAEt+ISO) groups. The extract was administered at a dose of 50 mg/kg body weight for 40 days orally by gavage and ISO was administered at a dose of 85 mg/kg body weight for two consecutive days intraperitoneally at an interval of 24 h. ISO induced myocardial infarction (MI) was confirmed by disturbances in serum lipid profile, heart tissue lipid peroxidation and antioxidant enzyme levels. There was a significant increase in the levels of serum total cholesterol (32.60 %), triglycerides (41.30 %), very low density lipoproteins (81.81 %), low density lipoproteins (84%) and phospholipids (38.88 %) and a significant decrease in the levels of high density lipoproteins (33.33 %) in the ISO control group when compared to normal controls. Additionally, there is a significant decrease in the levels of heart tissue antioxidant enzymes such as superoxide dismutase, catalase, glutathione reductase, glutathione peroxidase and depletion of reduced glutathione, which indicates enhanced lipid peroxidation(172 %). Pretreatment with extract significantly showed a protective effect against ISO altered lipid profile, lipid peroxidation and antioxidant enzyme levels. The present study showed therapeutic effect of TTFAEt on lipid profile and oxidative stress in isoproterenol (ISO) induced myocardial necrosis in experimental rats.


Employment-based abstinence reinforcement promotes opiate and cocaine abstinence in out-of-treatment injection drug users.
We examined the use of employment-based abstinence reinforcement in out-of-treatment injection drug users, in this secondary analysis of a previously reported trial. Participants (N = 33) could work in the therapeutic workplace, a model employment-based program for drug addiction, for 30 weeks and could earn approximately $10 per hr. During a 4-week induction, participants only had to work to earn pay. After induction, access to the workplace was contingent on enrollment in methadone treatment. After participants met the methadone contingency for 3 weeks, they had to provide opiate-negative urine samples to maintain maximum pay. After participants met those contingencies for 3 weeks, they had to provide opiate- and cocaine-negative urine samples to maintain maximum pay. The percentage of drug-negative urine samples remained stable until the abstinence reinforcement contingency for each drug was applied. The percentage of opiate- and cocaine-negative urine samples increased abruptly and significantly after the opiate- and cocaine-abstinence contingencies, respectively, were applied. These results demonstrate that the sequential administration of employment-based abstinence reinforcement can increase opiate and cocaine abstinence among out-of-treatment injection drug users.


Information processing in the hemisphere of the cerebellar cortex for control of wrist movement.
A region of cerebellar lobules V and VI makes strong loop connections with the primary motor (M1) and premotor (PM) cortical areas and is assumed to play essential roles in limb motor control. To examine its functional role, we compared the activities of its input, intermediate, and output elements, i.e., mossy fibers (MFs), Golgi cells (GoCs), and Purkinje cells (PCs), in three monkeys performing wrist movements in two different forearm postures. The results revealed distinct steps of information processing. First, MF activities displayed temporal and directional properties that were remarkably similar to those of M1/PM neurons, suggesting that MFs relay near copies of outputs from these motor areas. Second, all GoCs had a stereotyped pattern of activity independent of movement direction or forearm posture. Instead, GoC activity resembled an average of all MF activities. Therefore, inhibitory GoCs appear to provide a filtering function that passes only prominently modulated MF inputs to granule cells. Third, PCs displayed highly complex spatiotemporal patterns of activity, with coordinate frames distinct from those of MF inputs and directional tuning that changed abruptly before movement onset. The complexity of PC activities may reflect rapidly changing properties of the peripheral motor apparatus during movement. Overall, the cerebellar cortex appears to transform a representation of outputs from M1/PM into different movement representations in a posture-dependent manner and could work as part of a forward model that predicts the state of the peripheral motor apparatus.


Respiratory syncytial virus (RSV) outbreak in the NICU: description of eight cases.
Respiratory syncytial virus (RSV) has been recognized as a major nosocomial hazard on pediatric wards. Because of maternally acquired antibodies, symptomatic RSV infection is rare in term neonates. During an outbreak of RSV in our neonatal ICU, 12 infants (gestational age = 34 +/- 5 weeks) remained RSV negative. In contrast, eight preterm infants (gestational age = 28 +/- 2 weeks) became RSV positive. Four infants became very sick with RSV and required mechanical ventilation and support. Acute respiratory distress syndrome (ARDS) developed in two of them resulting in death of one of them. Control measures were effective in controlling the outbreak. We conclude that during an RSV outbreak in the neonatal ICU, the attack rate is higher in preterm infants born at lower gestational age resulting in significant mortality and morbidity.


Male mate choice for large gravid spots in a livebearing fish.
Male mate choice occurs in a wide range of species, and males can increase their reproductive success by distinguishing between females based on their fecundity (e.g., large body size) or their expected sperm competition risk (e.g., virgins). However, patterns of male mate choice could be mitigated by variation in female physiological receptivity, as males can benefit by directing their mating efforts toward females that are at a point in their reproductive cycle when fertilization probability is highest. Here, we perform three experiments to assess whether male mate choice is influenced by cues of female physiological receptivity, fecundity, or sperm competition risk in the pygmy halfbeak (Dermogenys collettei), a small livebearing fish. Female halfbeaks possess a "gravid spot"-an orange abdominal marking that is caused by pigmentation of the females' skin and variation in embryo development and pigmentation during pregnancy. We show that gravid spot size increases toward parturition and is largest right before giving birth, independent of abdominal width or body size. Males consistently chose females with large gravid spots over females with small gravid spots. In contrast, males did not prefer larger females over smaller females or virgin females over mated females. As female halfbeaks store sperm prior to fertilizations, we suggest that males use the size of the gravid spot as a cue to direct their mating efforts to those females where the chance of fertilization is highest.


Evaluation of the Prevalence and Risk Factors of Drug-Related Problems in Hypertension and Type 2 Diabetes Mellitus Patients at a Tertiary Care Hospital: A Cross-Sectional Study.
Background Drug-related problems (DRPs) potentially interfere with the desired treatment goals which may lead to increased healthcare costs, morbidity, and mortality. Despite the negative consequences of DRPs, there is a lack of comprehensive research on their prevalence and risk factors, particularly in chronic diseases such as hypertension and type 2 diabetes mellitus (DM). This study aims to evaluate the prevalence and contributing factors of DRPs among hypertension, type 2 DM, and hypertension with type 2 DM in the outpatient general medicine department. Methodology A hospital-based, prospective, observational study was conducted over three months. DRPs were classified using the Helper-Strand classification. The potential risk factors contributing to DRPs were assessed using binary and multinomial logistic regression methods. A p-value <0.05 was considered statistically significant. Results Among the 236 study participants, DRPs were more prevalent in males, and the mean age of the participants was 51.73 ± 9.47 years. DRPs were found in 76% of the study participants, and the mean number of DRPs per patient was 1.16 ± 0.45. Among the identified DRPs, suboptimal therapeutic goals (33%) were the most frequently observed, followed by ineffective drugs (32%), medication non-adherence (23%), and drug-drug interaction (5%). Therapeutic duplication and overdose were less commonly encountered as DRPs. The presence of comorbidity (adjusted odds ratio (AOR) = 5.77), and smoking (AOR = 21.07) were found to be significant risk factors (p < 0.05) contributing to DRPs. Conclusions DRPs are more prevalent in hypertension, type 2 DM, and hypertension with type 2 DM. Age range (40-60 years), comorbidity, and smoking were found to be associated with a higher incidence of DRPs. The implementation of a multidisciplinary team approach involving clinical pharmacists and physicians can effectively identify the prevalence and determine the associated risk factors of DRPs and subsequently may help employ targeted interventions to mitigate the development of DRPs.


Longterm followup and quality of life after hematopoietic stem cell transplantation.
The success of marrow or blood stem cell transplantation may depend upon events arising months to years later. Transplant regimen related toxicity may include cataract formation due to corticosteroids or total body irradiation (TBI) and endocrine or gonadal dysfunction requiring hormonal replacement. By 15 to 20 years post-transplant, the cumulative incidence of secondary malignancies (including skin cancers) ranges from 4% (no TBI) to 14% (prior irradiation) in patients with previous aplastic anemia. Chronic graft versus-host-disease (GVHD) develops in 33% of HLA-identical sibling transplants and requires 1 to 2 years of immunosuppressive therapy. In allograft recipients free of GVHD, there are very few late infections or complications. These findings are confirmed by multidimensional studies of the quality of life of adult patients surviving 6 to 18 years after marrow transplantation and demonstrate that 80% of patients rate their quality of life as good to excellent and 5%, as poor. Considerations of late effects of transplant and maintenance of quality of life are key considerations when weighing the risks and benefits of stem cell grafts for the treatment of severe autoimmune diseases. Careful followup and reporting of these initial patient cohorts will be vital in determining the longterm success of stem cell transplantation.


Improved external rotation with concomitant reverse total shoulder arthroplasty and latissimus dorsi tendon transfer: A systematic review.
In conjunction with reverse total shoulder arthroplasty (RSA), latissimus dorsi and teres major (LD-TM) transfer has been advocated in the setting of combined loss of elevation and external rotation. The purpose of this systematic review is to summarize the clinical outcomes following RSA with LD-TM transfer. A search of PubMed, EMBASE, CINAHL, Medline, and Cochrane databases was performed between January 1, 1990 and March 1, 2016 and included articles related to outcomes following RSA with LD-TM transfer. Primary outcomes of interest were constant score, shoulder range of motion, and patient satisfaction. Secondary outcomes of interest included subjective shoulder value, simple shoulder test, activities of daily living requiring external rotation, and visual analog pain score. Additional outcomes evaluated included complications and reoperations. Frequency-weighted values of outcome data were utilized. Five level IV studies involving 98 shoulders met the inclusion criteria. The mean age of the cohort was 69.1 ± 5.19 years (range 47-85). RSA with LD-TM transfer was performed for rotator cuff arthropathy (94%) or proximal humerus fracture (6%). The average follow-up was 44.5 ± 10.38 months (range 12-105 months). The constant score improved from 28 to 65 ( p < 0.0005). Active external rotation improved from -7.4° to 22.9° ( p < 0.0005). There was a 22.4% overall complication rate, including dislocation (5.1%), infection (5.1%), and transient nerve palsy (3.4%). Patients undergoing RSA with LD-TM transfer in the setting of loss of external rotation demonstrate reliable clinical improvements in shoulder function with complication rates which are comparable to RSA alone.


Resveratrol Ameliorates Arterial Stiffness Assessed by Cardio-Ankle Vascular Index in Patients With Type 2 Diabetes Mellitus.
Resveratrol has been reported to have potent anti-atherosclerotic effects in animal studies. However, there are few interventional studies in human patients with atherosclerogenic diseases. The cardio-ankle vascular index (CAVI) reflects arterial stiffness and is a clinical surrogate marker of atherosclerosis. The aim of the present study was to investigate the effect of resveratrol on arterial stiffness assessed by CAVI in patients with type 2 diabetes mellitus (T2DM).In this double-blind, randomized, placebo-controlled study, 50 patients with T2DM received supplement of a 100mg resveratrol tablet (total resveratrol: oligo-stilbene 27.97 mg/100 mg/day) or placebo daily for 12 weeks. CAVI was assessed at baseline and the end of study. Body weight (BW), blood pressure (BP), glucose and lipid metabolic parameters, and diacron-reactive oxygen metabolites (d-ROMs; an oxidative stress marker) were also measured.Resveratrol supplementation decreased systolic BP (-5.5 ± 13.0 mmHg), d-ROMs (-25.6 ± 41.8 U.CARR), and CAVI (-0.4 ± 0.7) significantly (P < 0.05) and decreased BW (-0.8 ± 2.1 kg, P = 0.083) and body mass index (-0.5 ± 0.8 kg/m2, P = 0.092) slightly compared to baseline, while there were no significant changes in the placebo group. Decreases in CAVI and d-ROMs were significantly greater in the resveratrol group than in the placebo group. Multivariate logistic regression analysis identified resveratrol supplementation as an independent predictor for a CAVI decrease of more than 0.5.In conclusion, 12-week resveratrol supplementation may improve arterial stiffness and reduce oxidative stress in patients with T2DM. Resveratrol may be beneficial in preventing the development of atherosclerosis induced by diabetes. However, a large-scale cohort study is required to validate the present findings.


Dinuclear ruthenium(ii) complexes with flexible bridges as non-duplex DNA binding agents.
The stereoisomers of a series of dinuclear ruthenium(ii) complexes [{Ru(phen)(2)}(2)(micro-BL)](4+) (phen = 1,10-phenanthroline) with flexible bridging ligands (BL) bb2 {1,2-bis[4(4'-methyl-2,2'-bipyridyl)]ethane}, bb5 {1,5-bis[4(4'-methyl-2,2'-bipyridyl)]pentane}, bb7 {1,7-bis[4(4'-methyl-2,2'-bipyridyl)]heptane}, and bb10 {1,10-bis[4(4'-methyl-2,2'-bipyridyl)]decane} have been synthesised. Their binding to a control dodecanucleotide, d(CCGGAATTCCGG)(2), and a tridecanucleotide, d(CCGAGAATTCCGG)(2), which contains a single adenine bulge have been studied using fluorescence displacement assays involving intercalating and groove-binding dyes, equilibrium dialysis and binding affinity chromatography. The fluorescence intercalator displacement (FID) assay indicated that LambdaLambda-[{Ru(phen)(2)}(2)(micro-bb7)](4+) had the greatest binding affinity with all the oligonucleotides, whereas an analogous fluorescence technique using a minor-groove binding dye, equilibrium dialysis and affinity binding chromatography showed that DeltaDelta-[{Ru(phen)(2)}(2)(micro-bb7)](4+) had the strongest binding. An (1)H NMR study of the binding of the DeltaDelta-enantiomer of [{Ru(phen)(2)}(2)(micro-bb7)](4+) to d(CCGAGAATTCCGG)(2) confirmed the selectivity of the metal complex for the bulge site and provided the basis for an energy-minimised binding model of the dinuclear ruthenium complex with the single adenine bulge containing trinucleotide. The binding model demonstrated the ability of the flexibly-linked complex to follow the curvature of the DNA minor groove.


Rac1 and a GTPase-activating protein, MgcRacGAP, are required for nuclear translocation of STAT transcription factors.
STAT transcription factors are tyrosine phosphorylated upon cytokine stimulation and enter the nucleus to activate target genes. We show that Rac1 and a GTPase-activating protein, MgcRacGAP, bind directly to p-STAT5A and are required to promote its nuclear translocation. Using permeabilized cells, we find that nuclear translocation of purified p-STAT5A is dependent on the addition of GTP-bound Rac1, MgcRacGAP, importin alpha, and importin beta. p-STAT3 also enters the nucleus via this transport machinery, and mutant STATs lacking the MgcRacGAP binding site do not enter the nucleus even after phosphorylation. We conclude that GTP-bound Rac1 and MgcRacGAP function as a nuclear transport chaperone for activated STATs.


Long-term follow-up and predictive factors of recurrence of anemia in a cohort of 102 very elderly patients explored for iron-deficiency anemia.
To evaluate long-term follow-up and predictors of relapse of anemia in a cohort of 102 very elderly patients previously explored for iron-deficiency anemia (IDA). One hundred and two patients [61 women and 41 men, mean age 82+/-5.8 y (75 to 98)] explored for IDA were prospectively followed up from inclusion (June 2003 to May 2005) until death or May 2006. Survival rate was estimated by the Kaplan-Meier method and compared by the log-rank test. Predictors of recurrence of anemia were identified by multivariate analysis in the 4 following subgroups: unexplained IDA (subgroup 1, n=27), benign lesion (subgroup 2, n=37), cancer treated curatively (subgroup 3, n=28), cancers treated palliatively (subgroup 4, n=10). Median follow-up was 20 months. At baseline, main clinical and laboratory data were not significantly different in the 4 subgroups, especially as regards severe comorbidities. Thirty-three patients died, 10 (30%) of them in the first month. Ten (100%) belonged to subgroup 4 versus, respectively, n=7 (26%), n=8 (22%), and n=8 (29%) of patients from subgroups 1, 2, and 3 (P<0.001). No death was directly related to recurrence of anemia. Survival rate at 1 year was 10% in subgroup 4, significantly lower than the other 3 subgroups (subgroup 1: 84%; subgroup 2: 86%; subgroup 3: 78%; log-rank test, P<0.0001). Anemia recurred in 18 cases, and required red cell transfusion in 13 cases. Predictive factors of recurrence of anemia [odds ratio (confidence interval 95%), P] were cancers treated palliatively [14.9 (3-72), P<0.01] and angiodysplasias [4.5 (1.1-18.2), 0.035]. In a cohort of very elderly patients explored for IDA, the mortality rate and the long-term survival were not different for patients with IDA related to a cancer treated curatively than those with unexplained IDA and those with IDA related to a benign lesion. Angiodysplasias and cancers treated palliatively were associated with recurrence of anemia. These results suggest interventionist strategies (including endoscopic investigation and appropriate surgery) for elderly patients with IDA.


Antioxidant and cardioprotective effects of Ilex cornuta on myocardial ischemia injury.
Previous studies have indicated that the Ilex genus exhibits antioxidant, neuroprotective, hepatoprotective, and anti-inflammatory activities. However, the pharmacologic action and mechanisms of Ilex cornuta against cardiac diseases have not yet been explored. The present study was designed to investigate the antioxidant and cardioprotective effects of Ilex cornuta root with in vitro and in vivo models. The anti-oxidative effects of the extract of Ilex cornuta root (ICR) were measured by 2, 2-diphenyl-1-picrylhydrazyl (DPPH) free-radical scavenging and MTT assays as well as immunoassay. Furthermore, a rat model of myocardial ischemia was established to investigate the cardioprotective effect of ICR in vivo. Eight compounds were isolated and identified from ICR and exhibited DPPH free-radical scavenging activities. They also could increase cell viability and inhibit morphological changes induced by H2O2 or Na2S2O4 in H9c2 cardiomyocytes, followed by increasing the SOD activities and decreasing the MDA and ROS levels. In addition, it could suppress the apoptosis of cardiomyocytes. In the rat model of myocardial ischemia, ICR decreased myocardial infarct size and suppressed the activities of LDH and CK. Furthermore, ICR attenuated histopathological alterations of heart tissues and the MDA levels, while increasing SOD activities in serum. In conclusion, these results suggest that ICR has cardioprotective activity and could be developed as a new food supplement for the prevention of ischemic heart disease.


[A protein related to the main core protein of the mouse mammary cancer virus in a microparticle fraction of human milk].
Virus-like density fractions (VDF) have been prepared from 6 specimens of human milk by ultracentrifugation of milk sera and recentrifugation of pellet through 35% sucrose or by separation in sucrose density gradient. Using electroblotting and enzyme-linked antibody probes, the protein with a molecular weight of 27 kD, reacting with serum against MMTV gag proteins, was identified in 5/6 of milk VDF. The absence (or very low amounts) of this protein among proteins of milk, fat globule membranes and cellular membranes of human milk has been demonstrated. Positive VDF decrease the activity of anti-p27 MMTV-specific serum and the activity of human sera reacting with p27 MMTV. A human protein immunologically related to the main gag protein of MMTV has been described; this protein seems to be an antigen causing the appearance of anti-MMTV antibodies in human sera.


Elucidation of the toxic mechanism of the plasticizers, phthalic acid esters, putative endocrine disrupters: effects of dietary di(2-ethylhexyl)phthalate on the metabolism of tryptophan to niacin in rats.
We have previously reported that the administration of a large amount of di(n-butyl)phthalate (DBP) increased the conversion ratio of tryptophan to niacin in rats. In the present experiment, the effect of di(2-ethylhexyl)phthalate (DEHP) on the conversion ratio and how altering the conversion ratio of tryptophan to niacin depended on the concentration of DEHP were investigated to elucidate the toxic mechanism of phthalic acid esters (PhE). Rats were fed with a diet containing 0%, 0.01%, 0.05%, 0.1%, 0.5%, 1.0%, or 3.0% DEHP for 21 days. To assess the conversion ratio of tryptophan to niacin, urine samples were collected at the last day of the experiment and measured for metabolites on the tryptophan-niacin pathway. The conversion ratio increased with increasing dietary concentration of DEHP above 0.05%; the conversion ratio was about 2% in the control group, whereas it was 28% in the 3.0% DEHP group. It is suggested that the inhibition of alpha-amino-beta-carboxymuconate-epsilon-semialdehyde decarboxylase (ACMSD) by DEHP or its metabolites caused this increase in the conversion ratio. We conclude that PhE such as DEHP and DBP disturbed the tryptophan-niacin metabolism.


Selective Interaction Between Chloroplast β-ATPase and TGB1L88 Retards Severe Symptoms Caused by Alternanthera mosaic virus Infection.
The multifunctional triple gene block protein 1 (TGB1) of the Potexvirus Alternanthera mosaic virus (AltMV) has been reported to have silencing suppressor, cell-to-cell movement, and helicase functions. Yeast two hybrid screening using an Arabidopsis thaliana cDNA library with TGB1 as bait, and co-purification with TGB1 inclusion bodies identified several host proteins which interact with AltMV TGB1. Host protein interactions with TGB1 were confirmed by biomolecular fluorescence complementation, which showed positive TGB1 interaction with mitochondrial ATP synthase delta' chain subunit (ATP synthase delta'), light harvesting chlorophyll-protein complex I subunit A4 (LHCA4), chlorophyll a/b binding protein 1 (LHB1B2), chloroplast-localized IscA-like protein (ATCPISCA), and chloroplast β-ATPase. However, chloroplast β-ATPase interacts only with TGB1L88, and not with weak silencing suppressor TGB1P88. This selective interaction indicates that chloroplast β-ATPase is not required for AltMV movement and replication; however, TRV silencing of chloroplast β-ATPase in Nicotiana benthamiana induced severe tissue necrosis when plants were infected by AltMV TGB1L88 but not AltMV TGB1P88, suggesting that β-ATPase selectively responded to TGB1L88 to induce defense responses.


The role of thioredoxin TrxA in Bacillus subtilis: a proteomics and transcriptomics approach.
Thiol-disulfide oxidoreductases of the thioredoxin superfamily are crucial for maintaining the thiol redox state in living organisms. For the bacterium Bacillus subtilis thioredoxin A (TrxA) was described as the product of an essential gene indicating a key role during growth. By means of mRNA profiling Smits et al. (J. Bacteriol. 2005, 187, 3921-3930) suggested a critical function for TrxA in sulfur utilization during stationary phase. We extended the analysis of TrxA to exponential growth and characterized a trxA conditional mutant by proteome analysis complemented by transcriptomics. After TrxA-depletion, the growth rate was dramatically decreased. The cells responded at mRNA and protein level by the increased expression of genes involved in the utilization of sulfur, which represents the most obvious response as visualized by gel-based proteomics. Furthermore, several genes of the antioxidant response were found at higher expression levels after TrxA-depletion. When sulfate was replaced by thiosulfate or methionine as sulfur source, the growth inhibition was abolished. In the presence of thiosulfate but in the absence of TrxA, the induction of the sulfur limitation response and the oxidative stress response was not observed. Our results show that the global change of gene expression is primarily caused by the interruption of the sulfate utilization after TrxA depletion. Thus, its function in sulfate assimilation renders TrxA an essential protein in growing B. subtilis cells.


Evidence for isoforms of 11 beta-hydroxysteroid dehydrogenase in the liver and kidney of the guinea pig.
In the human and in rodents like the rat and mouse, the liver enzyme 11 beta-hydroxysteroid dehydrogenase type I (11 beta-HSD-I) is a functional oxidoreductase preferring NADP+/NADPH as cosubstrate, while the renal isoenzyme (11 beta-HSD-II) prefers NAD+ as cosubstrate, and seems to be a pure oxidase and protects the tubular, mineralocorticoid (MC) receptor from occupancy by cortisol and corticosterone. We studied the enzyme kinetics of 11 beta-HSDs in kidney and liver microsomes of the guinea pig, a species whose zoological classification is still a matter of debate. With a fixed concentration of 10(-6) mol/l cortisol, liver and kidney microsomes preferred NAD+ to NADP+ (10(-3) mol/l) for the conversion to cortisone. Kidney microsomes converted cortisol to cortisone with K(m) values of 0.64 mumol/l and 9.8 mumol/l with NAD+ and NADP+ as cosubstrates respectively. The reduction of cortisone to cortisol was slow with kidney microsomes, but could be markedly enhanced by adding an NADH/NADPH regenerating system: with NADPH as preferred cosubstrate, the approximate K(m) was 7.2 mumol/l. This indicated the existence of both isoenzymes in the guinea pig kidney. Liver microsomes oxidized cortisol to cortisone with similar K(m) and Vmax values for NAD+ to NADP+ as cosubstrates (K(m) of 4.3 mumol/l and 5.0 mumol/l respectively). The NAD+ preference for the oxidation of 10(-6) mol/l cortisol described above may be due to a second, NAD(+)-preferring 11 beta-HSD with a K(m) of 1.4 mumol/l. In contrast to the kidney, liver microsomes actively converted cortisone to cortisol with a preference for NADPH (K(m): 1.2 mumol/l; Vmax: 467 nmol/min per mg protein). Thus, the main liver enzyme is similar to the oxidoreductase of other species (11 beta-HSD-I) and is also present in the kidney, while the main kidney enzyme is clearly NAD(+)-preferring. This kidney enzyme (analogous to 11 beta-HSD-II of other species) seems to be suitable for the protection of the MC receptor from the high free plasma cortisol levels of the guinea pig.


The association of SNPs in ADIPOQ, ADIPOR1, and ADIPOR2 with insulin sensitivity in a cohort of adolescents and their parents.
Few studies have examined the association of SNPs in the adiponectin (ADIPOQ) and adiponectin receptor 1 and 2 (ADIPOR1, ADIPOR2) genes with the euglycemic clamp, i.e. the gold standard measure of insulin sensitivity. The association of comprehensive tag SNPs in these genes with insulin sensitivity was examined in a cohort of adolescents and their parents. Probands and siblings (n=441, mean age=17.9 years) were recruited along with their parents (n=262, mean age=47.9 years). Typed SNPs included 21 SNPs in ADIPOQ, 7 SNPs in ADIPOR1, and 13 SNPs in ADIPOR2. Mixed model linear regression was used to test the association of SNPs with euglycemic-clamp derived insulin sensitivity. All analyses were stratified by race. After corrections to account for multiple testing and the linkage disequilibrium structure of the genes, one SNP in the ADIPOQ gene (rs822393) was significantly associated with insulin sensitivity in white subjects. In whites, six SNPs in ADIPOQ, one SNP in ADIPOR1 and one SNP in ADIPOR2 were associated with insulin sensitivity at the P<0.05 level. In African Americans, two SNPs in ADIPOR1 were associated with insulin sensitivity at the P<0.05 level. These results suggest that a variant in the ADIPOQ gene influences levels of insulin sensitivity and age may modify the effects of this variant. There are several other variants in ADIPOQ, ADIPOR1, and ADIPOR2 that may influence insulin sensitivity and these variants should be further investigated in other populations.


Activity of d,l-alpha-tocopherol (vitamin E) against cardiotoxicity induced by doxorubicin and doxorubicin with cyclophosphamide in mice.
The aim of this study was to investigate the cardioprotective activity of vitamin E against doxorubicin alone and doxorubicin in combination with cyclophosphamide in mice. Female BalbC/NIH mice were treated with vitamin E (100 IU/kg, orally) 24 hr before single bolus doses of doxorubicin (10 mg/kg, intravenously), or doxorubicin and cyclophosphamide (150 mg/kg, intraperitoneally). Non-treated animals served as negative controls, while positive control groups received doxorubicin or doxorubicin and cyclophosphamide. For evaluation, serum enzyme activity of aspartate aminotransferase (AST), lactate dehidrogenase (LDH), alpha-hydroxybutirate dehydrogenase (alpha-HBDH), and creatine kinase (CK) at 48 hr and histopathology examination of the heart tissue (Billigham rules) at 1.5 and 3 months followed to treatments were used. In sera of mice treated with vitamin E prior to doxorubicin, the creatine kinase and % alpha-HBDH activity were significantly reduced, compared to positive control. Histopathology changes (scored as 1.5 at 1.5 and 3 months respectively) were not significant compared to negative control at both time points of examination. In animals which received vitamin E before doxorubicin and cyclophosphamide, none of the serum enzymes was significantly reduced compared to positive control, but non-significant increase in AST and creatine kinase activity was detected (3% and 16.57% respectively). The degree of myocardial damage was significantly higher compared to non-treated group (2.0 and 2.5 at 1.5 and 3 months respectively). Current results show that vitamin E in single oral dose failed to inhibit acute cardiotoxic activity of doxorubicin, but suspended further progression of the heart muscle damage over the time. On the contrary, vitamin E did not attain any cardioprotection against doxorubicin and cyclophosphamide in combination.


Molecular Simulations of Disulfide-Rich Venom Peptides with Ion Channels and Membranes.
Disulfide-rich peptides isolated from the venom of arthropods and marine animals are a rich source of potent and selective modulators of ion channels. This makes these peptides valuable lead molecules for the development of new drugs to treat neurological disorders. Consequently, much effort goes into understanding their mechanism of action. This paper presents an overview of how molecular simulations have been used to study the interactions of disulfide-rich venom peptides with ion channels and membranes. The review is focused on the use of docking, molecular dynamics simulations, and free energy calculations to (i) predict the structure of peptide-channel complexes; (ii) calculate binding free energies including the effect of peptide modifications; and (iii) study the membrane-binding properties of disulfide-rich venom peptides. The review concludes with a summary and outlook.


Experiences with cortisone given orally.
The advantages of the oral administration of cortisone, when compared with cortisone given intramuscularly, include the more rapid appearance of therapeutic effects, which is of importance in the therapy of acute disease, and the faster dissipation of effects when the hormone is discontinued, which is of value when dangerous reactions occur. Oral dose schedules depend upon the degree of urgency or chronicity of the treated disease. In acute diseases the therapeutic results, in general, were disappointing. Cortisone may be of greater value in the long-term maintenance treatment of certain chronic diseases. By long-term therapy the authors mean practically continuous treatment until either the disease goes into spontaneous remission or undesirable effects of the drug require cessation of treatment. Critical selection of patients and constant supervision of therapy are vital to the successful administration of cortisone. Even with these precautions, however, the therapeutic use of cortisone must be regarded as experimental until the passage of time permits better appraisal of harmful effects.


Role of Parental Smoking in Severe Bronchiolitis: A Hospital Based Case-Control Study.
Objective. Bronchiolitis is one of the commonest causes of hospitalization of infants and young children in Bangladesh. About 21% of under 5 children attending different hospitals of Bangladesh have bronchiolitis. Fifty percent (50%) men and three percent (3%) women of Bangladesh are smokers. Parental smoking is an important risk factor for both susceptibility and severity of bronchiolitis. The aim of this study was to find out the role of parental smoking in severe bronchiolitis. Design. Case-control study. Place and Duration of Study. The study was conducted in the Department of Paediatrics, Sylhet MAG Osmani Medical College Hospital, Bangladesh, from July 2013 to December 2015. Patients and Methods. Sixty-four patients admitted into the ward with severe bronchiolitis were enrolled as cases and sixty-four suitably matched apparently healthy children attending EPI centre and outpatient department presenting with nonrespiratory illness were enrolled as controls. Sample size was calculated using Guilford and Frucher formula. The technique was systematic random sampling. Every second case satisfying the inclusion and exclusion criteria was enrolled in the study. Results. The mean age of the patients was 7.53 (SD ± 4.75) months. Forty (62.5%) patients were male and twenty four (37.5%) patients were female. Male-to-female ratio was 1.7 : 1. Most of the cases (60.95%) came from low socioeconomic background. More than half of the cases (53.13%) were not exclusively breastfed babies. Mean length of hospital stay was 6.41 (SD ± 2.82) days. Thirty eight (59%) cases and twenty six (34%) controls were exposed to parental smoking. Result was highly significant (p = 0.005). Odds ratio was 2.8 (95% CI from 1.36 to 5.72). Conclusion. Exposure to parental smoking causes a statistically significant (p = 0.005, odds ratio = 2.8) increase in the risk of developing severe bronchiolitis in the first year of life.


Microbial production of hydrogen: an overview.
Production of hydrogen by anaerobes, facultative anaerobes, aerobes, methylotrophs, and photosynthetic bacteria is possible. Anaerobic Clostridia are potential producers and immobilized C. butyricum produces 2 mol H2/mol glucose at 50% efficiency. Spontaneous production of H2 from formate and glucose by immobilized Escherichia coli showed 100% and 60% efficiencies, respectively. Enterobactericiae produces H2 at similar efficiency from different monosaccharides during growth. Among methylotrophs, methanogenes, rumen bacteria, and thermophilic archae, Ruminococcus albus, is promising (2.37 mol/mol glucose). Immobilized aerobic Bacillus licheniformis optimally produces 0.7 mol H2/mol glucose. Photosynthetic Rhodospirillum rubrum produces 4, 7, and 6 mol of H2 from acetate, succinate, and malate, respectively. Excellent productivity (6.2 mol H2/mol glucose) by co-cultures of Cellulomonas with a hydrogenase uptake (Hup) mutant of R. capsulata on cellulose was found. Cyanobacteria, viz., Anabaena, Synechococcus, and Oscillatoria sp., have been studied for photoproduction of H2. Immobilized A. cylindrica produces H2 (20 ml/g dry wt/h) continually for 1 year. Increased H2 productivity was found for Hup mutant of A. variabilis. Synechococcus sp. has a high potential for H2 production in fermentors and outdoor cultures. Simultaneous productions of oxychemicals and H2 by Klebseilla sp. and by enzymatic methods were also attempted. The fate of H2 biotechnology is presumed to be dictated by the stock of fossil fuel and state of pollution in future.


[The onchocercal nodule].
The morphology of adults worms (male and female) is characteristic particularly the content of the uterus in the female worm and the fact that the organs do not fill the body cavity.


Multinutrient fortification of human breast milk for preterm infants following hospital discharge.
Preterm infants are usually growth restricted at hospital discharge. Feeding preterm infants after hospital discharge with multinutrient fortified breast milk rather than unfortified breast milk may facilitate more rapid catch-up growth and improve neurodevelopmental outcomes. To determine the effect of feeding preterm infants following hospital discharge with multinutrient fortified human breast milk versus unfortified breast milk on growth and development. We used the standard search strategy of the Cochrane Neonatal Review Group. This included electronic searches of the Cochrane Central Register of Controlled Trials Register (CENTRAL, The Cochrane Library, 2012, Issue 3), MEDLINE, EMBASE and CINAHL (until August 2012), conference proceedings, and previous reviews. Randomised or quasi-randomised controlled trials that compared feeding preterm infants following hospital discharge with multinutrient fortified breast milk compared with unfortified human breast milk. We extracted data using the standard methods of the Cochrane Neonatal Review Group with separate evaluation of trial quality and data extraction by two review authors and synthesis of data using risk ratio, risk difference and mean difference. We identified two small trials involving a total of 246 infants. These did not provide evidence that multinutrient fortification of breast milk for three to four months after hospital discharge affected rates of growth during infancy. One trial assessed infants at 18 months corrected age and did not find any statistically significant effects on neurodevelopmental outcomes. The limited available data do not provide convincing evidence that feeding preterm infants with multinutrient fortified breast milk compared with unfortified breast milk following hospital discharge affects important outcomes including growth rates during infancy. There are no data on long-term growth. Since fortifying breast milk for infants fed directly from the breast is logistically difficult and has the potential to interfere with breast feeding, it is important to determine if mothers would support further trials of this intervention.


Inoculum effects of cefepime/zidebactam (WCK 5222) and ertapenem/zidebactam (WCK 6777) for Enterobacterales in relation to β-lactamase type and enhancer effect, as tested by BSAC agar dilution.
Combinations of PBP3-active β-lactams with developmental diazabicyclooctanes (DBOs), e.g. zidebactam, remain active against many MBL producers via an enhancer effect. We explored how this activity is affected by inoculum. MICs of zidebactam and its cefepime and ertapenem combinations (WCK 5222 and WCK 6777, respectively) were determined by BSAC agar dilution at inocula from 3-6 × 103 to 3-6 × 105 cfu/spot. Isolates, principally Klebsiella spp., were chosen as having previously tested resistant to zidebactam or its cefepime combination, and by β-lactamase type. MICs of zidebactam, tested alone, were strongly inoculum dependent regardless of β-lactamase type; MICs of its cefepime and ertapenem combinations likewise were strongly inoculum dependent-rising ≥32-fold across the inoculum range tested-but only for MBL producers. Combination MICs for isolates with non-MBLs, including those with OXA-48 (where the enhancer effect remains critical for ertapenem/zidebactam) were much less inoculum dependent, particularly for cefepime/zidebactam. MBL producers frequently moved between putative 'susceptible' (MIC ≤ 8 + 8 mg/L) and 'resistant' (MIC > 8 + 8 mg/L) categories according to whether the inoculum was at the high or low end of BSAC's acceptable (1-4 × 104 cfu/spot) range. The activity of zidebactam combinations against MBL producers, which strongly depends on the enhancer effect, is inoculum dependent. Animal data suggest consistent in vivo activity even in high-inoculum pneumonia models. Contingent on this being supported by clinical experience, the combination behaviour may be best represented by the MICs obtained at the lower end of BSAC's inoculum range.


Glycophenotype of breast and prostate cancer stem cells treated with thieno[2,3-b]pyridine anticancer compound.
Tumor progression may be driven by a small subpopulation of cancer stem cells (CSCs characterized by CD44+/CD24- phenotype). We investigated the influence of a newly developed thienopyridine anticancer compound (3-amino-5-oxo-N-naphthyl-5,6,7, 8-tetrahydrothieno[2,3-b]quinoline-2-carboxamide, 1) on the growth, survival and glycophenotype (CD15s and GM3 containing neuraminic acid substituted with acetyl residue, NeuAc) of breast and prostate cancer stem/progenitor-like cell population. MDA-MB-231 and Du-145 cells were incubated with compound 1 alone or in combination with paclitaxel. The cellular metabolic activity was determined by the 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) assay. The type of cell death induced by 48-h treatment was assessed using a combination of Annexin-V-FITC and propidium iodide staining. Flow cytometric analysis was performed to detect the percentage of CD44+/CD24- cells, and GM3 and CD15s positive CSCs, as well as the expression of GM3 and CD15s per one CSC, in both cell lines. Compound 1 produces a dose- and time-dependent cytotoxicity, mediated mainly by apoptosis in breast cancer cells, and slightly (2.3%) but statistically significant lowering breast CSC subpopulation. GM3 expression per one breast CSC was increased, and the percentage of prostate GM3+ CSC subpopulation was decreased in cells treated with compound 1 compared with non-treated cells. The percentage of CD15s+ CSCs was lower in both cell lines after treatment with compound 1. Considering that triple-negative breast cancers are characterized by an increased percentage of breast CSCs and knowing their association with an increased risk of metastasis and mortality, compound 1 is a potentially effective drug for triple-negative breast cancer treatment.


Should magnetic resonance imaging or computed tomography be the primary brain imaging modality in the transient ischemic attack clinic?
The Royal College of Physicians and National Institute of Clinical Excellence have recommended that magnetic resonance imaging should be the modality of choice for cerebral imaging in transient ischemic attack patients. However, implementation of this is often difficult. Therefore, it is important to know whether magnetic resonance imaging contributes significantly to early clinical management in transient ischemic attack patients. A retrospective case-notes review of 65 consecutive patients seen by one neurology trainee (with consultant review), in a neurovascular service where computed tomography has been the primary cerebral imaging modality. Outpatient TIA/Neurovascular clinic at Imperial College hospital. 65 consecutive patients seen by one neurology trainee (with consultant review). We recorded the preliminary clinical diagnosis, details of investigations performed and whether or not patients had a magnetic resonance imaging brain scan subsequently, the number followed up in clinic and the final diagnosis. Of the 65 cases seen, 55% were classified initially as transient ischemic attack/stroke mimics. Of the 29 cases (45%) that were classified as transient ischemic attack, all had computed tomography scans, 12 had magnetic resonance imaging scans subsequently and 14 were followed up several weeks later. Of the 36 cases classified as stroke mimics, 27 had computed tomography scans immediately and 31 had carotid Dopplers, six subsequently had magnetic resonance imaging scans and 14 were followed up in clinic. Only two patients had their diagnosis revised on the basis of the magnetic resonance imaging. Our study suggests that magnetic resonance imaging brain changes the diagnosis in a relatively small percentage of cases. A good history and examination remain paramount in the assessment of patients presenting to the transient ischemic attack clinic, particularly when more than 50% of cases referred are transient ischemic attack/stroke mimics.


The rate of tension recovery in cardiac muscle correlates with the relative residual tension prevailing after restretch.
Isolated cardiac muscles generate tension more quickly at higher levels of Ca(2+) activation. We investigated the molecular mechanisms underlying this effect in permeabilized rat myocardial preparations by measuring the rate of tension recovery following brief shortening/restretch perturbations. Separate series of experiments used Ca(2+)-activating solutions with different pH values (pH 6.75, 7.00, and 7.25) and different phosphate (P(i)) concentrations (0, 2.5, and 5.0 mM added P(i)) to modulate the recovery kinetics. Subsequent analysis showed that the rate of tension recovery correlated (P < 0.001) with the relative residual tension, that is, the minimum tension measured immediately after restretch normalized to the steady-state isometric tension for the experimental condition. This new finding suggests that the rate at which cardiac muscles develop force increases with the proportion of cross bridges bound to the thin filament and is strong evidence of cooperative contractile activation.


Magnitude of Obesity/Overweight and Its Associated Factors Among HIV/AIDS Patients on Antiretroviral Therapy in Jimma Zone Hospitals, South West Ethiopia: Hospital-Based Cross-Sectional Study.
Obesity is on the rise worldwide, not only in the general population but also in PLWHA. Being overweight and obese are themselves risk factors for cardiovascular and other diseases. Despite this, few studies have been conducted to determine the magnitude of obesity/overweight and its associated factors among HIV/AIDS patients in Ethiopia, which necessitates this study. Hospital-based cross-sectional study was conducted from December to January 2019 at selected Jimma zone hospitals. WHO STEP-wise approach to chronic disease risk factor surveillance (STEPS) questionnaire and document review for HIV-related clinical factors was applied. Weight, height and waist circumference and hip circumference were measured. Data were analyzed using SPSS version 20. A total of 252 participants with a response rate of 95.8% were included. The prevalence of obesity/overweight was 21%. After adjusting for these variables, age category of greater than 50 years [AOR = 0.4, 95% CI (0.2, 0.9), p = 0.03], WHO clinical stage III and above [AOR = 0.04, 95% CI (0.002, 0.6), p = 0.02], presence of mild to moderate physical activity [AOR = 1.3, 95% CI (5.5, 33.3), p ≤ 0.001)], plasma CD4 count between 351 and 500 copies/mL [AOR=0.15, 95% CI (0.04, 0.6) p=0.024], and female sex [AOR = 2.6, 95% CI (1.25, 10) p=0.03)] were significantly associated with obesity/overweight. There was a high prevalence of obesity/overweight among HIV/AIDS patients. It was found that older age, female sex, early stage of the disease, lower CD4 count and presence of mild to moderate physical activity were significant predictors of obesity/overweight. Clinicians should be aware of the health consequence of obesity and consider instituting targeted weight management programs as a part of routine HIV care.


The effect of blood removal on oxidation and shelf life of broiler breast meat.
Blood components, especially hemoglobin, are powerful promoters of lipid oxidation and may decrease the shelf life of meat products. Therefore, this study examined different slaughter techniques to determine their effects on pH (24 h), color (L*a*b* values at 24 h), lipid oxidation, residual hemoglobin concentration (24 h), and sensory evaluation (d 1 and 4 postmortem; PM) in broiler breast fillets. The treatments included 1) CO(2) slaughter and not bled, 2) no stunning and bled, 3) electrical stunning (ES) and bled, 4) CO(2) stunning and bled, and 5) ES and decapitation. The birds were conventionally processed, and analyses were performed at 24 h PM except residual hemoglobin for which the samples were frozen (-80 degrees C) until analyses ( < 2 mo). There were no significant differences in pH or b* values at 24 h PM among any of the treatments. L* values were significantly higher, indicating lighter fillets in the ES and decapitated birds compared with the darker fillets from the CO(2) stunned and bled birds. The CO(2) slaughter and not bled birds had significantly higher a* values, indicating more red color, when compared with the ES and bled and decapitated birds. There were no significant differences in the residual hemoglobin contents in the broiler breast muscle when comparing all of the treatments except CO(2) slaughter and not bled, which was significantly (around 15%) greater. Overall TBA-reactive substances (TBARS; raw, cooked at 24 h, and cooked at 72 h PM) indicated that ES and bled birds had the lowest TBARS when compared with the remaining treatments. Consumer panels detected increased aroma (chicken meaty and warmed-over aromas) and flavor (chicken meaty and warmed-over flavors) in not bled samples at 24 h PM. By 72 h PM, however, there were no significant differences in aroma or flavor. Therefore, different slaughter and bleeding method may affect color and sensory properties of the broiler breast fillets, and the ES and decapitation method had the most favorable results for sensory quality.


The paradox of negative pressure wound therapy--in vitro studies.
Negative-pressure wound therapy (NPWT) has revolutionised wound care. Yet, it is still not understood how hypobaric tissue pressure accelerates wound healing. There is very little reported on the relevant physics of any substance subjected to suction in this manner. The common assumption is that applying suction to a substance is likely to result in a reduction of pressure in that substance. Although more than 250 research articles have been published on NPWT, there are little data verifying whether suction increases or decreases the pressure of the substance it is applied to. Clarifying this basic question of physics is the first step in understanding the mechanism of action of these dressings. In this study, pressure changes were recorded in soft plasticene and processed meat, using an intracranial tissue pressure microsensor. Circumferential, non-circumferential and cavity NPWT dressings were applied, and pressure changes within the underlying substance were recorded at different suction pressures. Pressures were also measured at 1cm, 2 cm and 3 cm from the NPWT placed in a cavity. In all three types of NPWT dressings, the underlying substance pressure was increased (hyperbaric) as suction pressure increased. Although there was a substantial pressure increase at 1cm, the rise in pressure at the 2-cm and 3-cm intervals was minimal. Substance pressure beneath all types of NPWT dressing is hyperbaric in inanimate substances. Higher suction pressures generate greater substance pressures; however, the increased pressure rapidly dissipates as the distance from the dressing is increased. The findings of this study on inanimate objects suggest that we may need to review our current perception of the physics underlying NPWT dressings. Further research of this type on living tissues is warranted.


Effect of dietary nickel on growth, urease activity, blood parameters and tissue mineral concentrations in the neonatal pig.
Day-old pigs were individually fed a low nickel (0.16 ppm) liquid milk-based diet supplemented with either 0, 5 or 25 ppm nickel on a dry matter basis for a 21-day period. At the end of the liquid feeding period, five pigs per treatment were killed, and the remaining five were fed a dried skim milk-based diet (0.12 ppm nickel) with similar levels of added nickel for an additional 28 days. Dietary nickel did not affect animal gain, liver cholesterol, serum protein concentrations or bacterial urease activity in the gastrointestinal tract. The addition of 5 ppm nickel to the basal dry diet reduced ammonia concentrations in the cecum by 33%. Pigs receiving the high level of nickel had decreased serum alkaline phosphatase and increased serum glucose at 49 days, compared to controls. Animals receiving 5 ppm nickel had higher liver iron and zinc concentrations than controls at 21 days but not at 49 days. Control pigs had lower kidney and lung nickel concentrations than animals receiving 5 ppm nickel at 21 days but not at 49 days. Increasing dietary nickel from 5 to 25 ppm resulted in increased concentrations of nickel in serum, kidney, lung, spleen and muscle. These results suggest that 0.12-0.16 ppm nickel is adequate for growth of neonatal pigs fed milk-based diets. However, additional nickel may improve the iron and zinc status of the young pig.


Novel Antifungal Compounds Discovered in Medicines for Malaria Venture's Malaria Box.
Similarities in fungal and animal cells make antifungal discovery efforts more difficult than those for other classes of antimicrobial drugs. Currently, there are only three major classes of antifungal drugs used for the treatment of systemic fungal diseases: polyenes, azoles, and echinocandins. Even in situations where the offending fungal organism is susceptible to the available drugs, treatment courses can be lengthy and unsatisfactory, since eradication of infection is often very difficult, especially in individuals with impaired immunity. Consequently, there is a need for new and more effective antifungal drugs. We have identified compounds with significant antifungal activity in the Malaria Box (Medicines for Malaria Ventures, Geneva, Switzerland) that have higher efficacy than some of the currently used antifungal drugs. Our best candidate, MMV665943 (IUPAC name 4-[6-[[2-(4-aminophenyl)-3H-benzimidazol-5-yl]methyl]-1H-benzimidazol-2-yl]aniline), here referred to as DM262, showed 16- to 32-fold-higher activity than fluconazole against Cryptococcus neoformans. There was also significant antifungal activity in other fungal species with known antifungal resistance, such as Lomentospora prolificans and Cryptococcus gattii. Antifungal activity was also observed against a common fungus, Candida albicans. These results are important because they offer a potentially new class of antifungal drugs and the repurposing of currently available therapeutics. IMPORTANCE Much like the recent increase in drug-resistant bacteria, there is a rise in antifungal-resistant strains of pathogenic fungi. There is a need for novel and more potent antifungal therapeutics. Consequently, we investigated a mixed library of drug-like and probe-like compounds with activity in Plasmodium spp. for activity against two common fungal pathogens, Cryptococcus neoformans and Candida albicans, along with two less common pathogenic species, Lomentospora prolificans and Cryptococcus gattii. We uncover a previously uncharacterized drug with higher broad-spectrum antifungal activity than some current treatments. Our findings may eventually lead to a compound added to the arsenal of antifungal therapeutics.


Evaluation of antiproliferative agents using a cell-culture model.
Chinese hamster ovarian (CHO) cells in culture were used to evaluate the relative antiproliferative potential of drugs. These agents have been used to improve the clinical response after glaucoma filtering surgery. The following drugs were evaluated: 5-fluorouracil (5-FU) as the benchmark, 5-fluorouridine (FUR), 5-fluorodeoxyuridine (FUDR), 5'-deoxy-5-fluorouridine (DFUR), bleomycin, and cytarabine (ARA-C). In addition to cell counting, a colorimetric assay based on the tetrazolium salt, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) was used to follow growth response. The MTT assay was found to be extremely convenient and an indirect measure of cell activity, offering an alternate or addition to a measure of cell number. All agents tested were shown to inhibit cellular proliferation. Dose-response curves for each agent indicate the following absolute potency: FUDR greater than FUR greater than ARA-C greater than 5-FU = bleomycin greater than DFUR. Besides absolute potency, an evaluation of the effects of equivalent inhibitory concentrations of each drug on growth rate was assessed. Several agents affected the proliferation rate patterns differently. Based on these studies, it is suggested that the in vitro model can identify potential agents through an assessment of their overall activity profile in CHO cells, which includes not only their potency based on dose response, but their onset of activity, duration of effect, and potential for toxicity.


Severe ischemia after radial artery catheterization: A literature review of published cases.
Severe ischemia is a rare complication of radial artery catheterization (RAC). This study aims to summarize risk factors of RAC-elicited severe hand ischemia, preventive, and therapeutic management. Literature search was conducted in eight electronic English and Chinese databases to identify relevant published cases. Data of interest was extracted and analyzed. Database search identified 28 articles reporting cases of 57 patients developing hand ischemia following RAC. Patients aged between 1 day and 88 years. The indications for RAC included surgery, shock, cardiac arrest, and Neonatal Intensive Care Unit (NICU) admission. Identified risk factors included pre-existing vascular diseases, hypotension, arterial anatomical abnormality or small diameter, vasoconstrictors, and catheter-related problems. Totally, 18 patients complained pain; 32 developed discoloration; 19 pulselessness; 3 paresthesia; 13 swolleness and 19 coldness. Eventually, 30 patients recovered well, but 20 patients unfortunately underwent digital amputation and three patients deceased due to non-RAC-related causes. Severe hand ischemia following RAC is a rare complication, with the reported incidence of approximately 0.09%. There is no definite predictor for RAC-related hand ischemia, but patients with risk factors are prone to the occurrence of hand ischemia. It's vital to initiate early recognition and proactive strategies for a best practice RAC insertion.


A mutation in the canine BHD gene is associated with hereditary multifocal renal cystadenocarcinoma and nodular dermatofibrosis in the German Shepherd dog.
Hereditary multifocal renal cystadenocarcinoma and nodular dermatofibrosis (RCND) is a naturally occurring canine kidney cancer syndrome that was originally described in German Shepherd dogs. The disease is characterized by bilateral, multifocal tumors in the kidneys, uterine leiomyomas and nodules in the skin consisting of dense collagen fibers. We previously mapped RCND to canine chromosome 5 (CFA5) with a highly significant LOD score of 16.7 (theta=0.016). We have since narrowed the RCND interval following selection and RH mapping of canine genes from the 1.3 x canine genome sequence. These sequences also allowed for the isolation of gene-associated BACs and the characterization of new microsatellite markers. Ordering of newly defined markers and genes with regard to recombinants localizes RCND to a small chromosomal region that overlaps the human Birt-Hogg-Dubé locus, suggesting the same gene may be responsible for both the dog and the phenotypically similar human disease. We herein describe a disease-associated mutation in exon 7 of canine BHD that leads to the mutation of a highly conserved amino acid of the encoded protein. The absence of recombinants between the disease locus and the mutation in US and Norwegian dogs separated by several generations is consistent with this mutation being the disease-causing mutation. Strong evidence is provided that the RCND mutation may have a homozygous lethal effect (P<0.01).


Prevalence of Irritable Bowel Syndrome in Saudi Arabia: A Systematic Review and Meta-Analysis.
Irritable bowel syndrome (IBS) is a commonly found global functional pathology with no detectable structural changes. It affects the quality of life and often coexists with psychiatric and somatic issues. We reviewed all articles published between 1990 and April 2023. The databases used for the data search were Google Scholar, Web of Science, Cochrane Library, and PubMed/MEDLINE. Ovid search engine was also used to broaden the search strategy. Predefined keywords, including "Irritable bowel syndrome" (MeSH) OR "IBS" (all fields), along with "Saudi Arabia" and "Middle East," were used to avoid data loss and ambiguity. Any cross-sectional study that reported the prevalence of IBS in any gender, age, and group of the Saudi population was included. Data extraction was independently performed in duplicate to mitigate bias and data loss. Statistical analysis of proportion was conducted by using Miller (Freeman-Tukey double arcsine - exact inverse). Out of 350 records identified, only 38 studies were included in the quantitative synthesis. The total number of study participants was 26,567, on the basis of the predefined inclusion criteria of the study. StatsDirect software was used for the statistical analysis of the study parameters. Based on all 38 identified studies, the calculated pooled prevalence was 20.7% (95% confidence interval (CI) = 17.8% to 23.7% by applying random effects (DerSimonian-Laird method). IBS was identified in 21% (95% CI = 16.7% to 25.7%) of the general population, 22% (95% CI = 17.6% to 26.7%) of students, and 18.3% (95% CI = 13.3% to 23.9%) of healthcare workers. The pooled prevalence of IBS among the Saudi population was 20.7%. The pathophysiology of IBS is complexed and significantly affected by genetics, diet, cultural characteristics, age, anxiety, depression, stress, and sleep disorders. This study fills a gap in understanding IBS prevalence in Saudi Arabia, contributing valuable data to this region.


[Hyperfractionated irradiation of bronchial cancer. Results of a pilot study].
The results achieved during recent years in experimental radiotherapy of malignant tumors show more and more the benefit provided by the small individual doses applied in fractionated irradiation. The effects and side effects of a hyperfractionated therapy of the bronchial carcinoma were investigated in a not randomized comparative study. The data of 100 patients were available for evaluation; they showed a tendency to local superiority of hyperfractionated irradiation. The value of hyperfractionation shall be examined in detail in a randomized prospective study.


Human resources in healthcare.
This issue of World Health & Population presents papers that have been published online by WHP and are selected here as representative of recent outstanding contributions to the journal. The papers in this issue include research from South and Southeast Asia, Africa and Latin America.


Learner-centered online courses/programs in gerontology and geriatrics: new responses to changing needs of health professionals.
This article describes recent trends that have led to an emphasis on a learner-centered approach to gerontology and geriatrics education especially in distance-based education. A learner-centered approach to education has combined with technological advances to stimulate distance-enhanced education for students in geriatric and gerontology programs. The technological advances, especially the Internet, that have enhanced the capacity of educational programs to involve students in the learning process even though separated from the instructor by time and distance, are discussed. In response to the needs of health care professionals who were seeking to enhance their skills in research, education, and leadership in their respective professions, including gerontology, the learner-centered Doctoral Program in Health-Related Sciences (DPHRS) was established in the School of Allied Health Professions of Virginia Commonwealth University. The specifics of this distance-enhanced, learner-centered program are described. The article ends with strategies for encouraging a learner-centered experience with special focus on distance-based education.


Bilateral cystic nephroma with pleuropulmonary blastoma.
Cystic nephroma is a rare benign renal neoplasm that is purely cystic and is lined by an epithelium. Bilateral cystic nephromas are even rarer with only a handful cases reported in the literature. A case of a 2-year-old male child who presented with bilateral renal cystic masses later diagnosed as cystic nephromas is presented here. Ultrasound, CT scan and histopathological investigations aided in arriving at the correct diagnosis. The most concerning feature was the presence of a fluid filled cystic mass in the lungs, most probably a pleuropulmonary blastoma which is a rare malignant neoplasm known to be associated with bilateral cystic nephromas. The most common presenting symptoms of cystic nephroma are painless abdominal mass, abdominal or flank pain and haematuria. These tumours usually follow a benign course and nephrectomy alone is curative. A close surveillance of such patients is recommended because of elevated risk of other tumours.


Phase II study of carboplatin and erlotinib (Tarceva, OSI-774) in patients with recurrent glioblastoma.
Targeting the epidermal growth factor receptor (EGFR) may be effective in a subset of glioblastoma patients. This phase II study assessed the clinical activity of erlotinib plus carboplatin and to determine molecular predictors of response. The primary endpoint was progression free survival (PFS). Patients with recurrent glioblastoma with no more than two prior relapses received carboplatin intravenously on day 1 of every 28-day cycle (target AUC of 6 mg x ml/min). Daily erlotinib at 150 mg/day was dose escalated to 200 mg/day, as tolerated. Clinical and MRI assessments were made every 4 and 8 weeks, respectively. Tumor tissue was evaluated for EGFR, AKT and phosphatase and tensin homolog (PTEN) status. One partial response (PR) was observed out of 43 assessable patients. Twenty patients (47%) had stable disease (SD) for an average of 12 weeks. Median PFS was 9 weeks. The 6-month PFS rate was 14%. Median overall survival (OS) was 30 weeks. This regimen was well tolerated with grade 3/4 toxicities of fatigue, leukopenia, thrombocytopenia and rash requiring dose reductions. A recursive partitioning analysis (RPA) predicted that patients with KPS >or=90 treated with more than 1 prior regimen had the highest OS. No correlation was observed between EGFR, Akt or PTEN expression and either PFS or OS. Carboplatin plus erlotinib is well tolerated but has modest activity in unselected patients. Future trials should be stratified based on optimal molecular or clinical characteristics.


Comparison and immunobiological characterization of retinoic acid inducible gene-I-like receptor expression in mesenchymal stromal cells.
Due to their immunomodulatory and regenerative properties, Mesenchymal stromal cells (MSC) have generated major interests in several clinical settings including transplantation and inflammatory diseases. MSC functions can be influenced by their tissue origin. Their microenvironment strongly affects their biology notably through TLR sensing. In this study, we show that MSC isolated from four different sources express another type of cytosolic pathogen recognition receptors known as retinoic acid inducible gene-I (RIG-I)-like receptors (RLR). RLR activation in MSC induces the production of Type I IFN (IFN-β) and Type III IFN (IFN-λ1). The highest producers are adipose tissue(AT)-MSC. We further show that Interferon production is induced through TBK1/IKK-ε signaling and IRF7 phosphorylation. Depending on MSC source, the knockdown of TLR3 and/or RIG-I decreases the MSC response to RLR ligand poly(I:C)/Lyovec. Among the different MSC types, AT-MSCs display the highest sensitivity to viral stimuli as shown by the alteration of their viability after prolonged stimulation. Our work indicates that this could be linked to an increase of pro-apoptotic Noxa expression. Finally, the expression of IDO1 and LIF upon RLR activation indicate the increase of MSC immunomodulatory potential, especially in AT-MSCs. Altogether, these data should be considered when designing MSC-based therapy in clinical settings where inflammation or infection are present.


Mayer-Rokitansky-Küster-Hauser syndrome as an interdisciplinary problem.
The Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome, also known as Müllerian agenesis or aplasia, is a congenital disease manifested by the aplasia of the uterus and the upper 2/3 of the vagina; its incidence is 1 in 4,000-5,000 female live births. We can distinguish 2 types of the MRKH syndrome: type I, which is characterized by an isolated absence of 2/3 of the vagina and uterus; and type II or MURCS (Müllerian duct aplasia, unilateral renal agenesis and cervicothoracic somite anomalies), which is also associated with other symptoms. The treatment of the MRKH syndrome patients aims at creating a neovagina and enabling sexual intercourse. Non-surgical techniques are the first-choice methods, and more than 90% of patients notice an anatomical and functional improvement if they are well-prepared emotionally. If non-surgical treatment does not bring about the expected results, a surgical procedure remains an option. The surgical method is mainly determined by the surgeon's experience. There are a few types of operations, though none of them seems superior to others. The next challenge is to provide these patients with a chance to become parents. Nowadays, a uterine transplant, a surrogate or adoption are the available solutions. An interdisciplinary approach is required, and the treatment should consist of medical and psychological support. This review presents the current knowledge about the MRKH syndrome with regard to the current methods of non-surgical and surgical treatment as well as a summary of the associated psychological problems.


Unique mechanism of the interaction between honey bee toxin TPNQ and rKir1.1 potassium channel explored by computational simulations: insights into the relative insensitivity of channel towards animal toxins.
The 21-residue compact tertiapin-Q (TPNQ) toxin, a derivative of honey bee toxin tertiapin (TPN), is a potent blocker of inward-rectifier K(+) channel subtype, rat Kir1.1 (rKir1.1) channel, and their interaction mechanism remains unclear. Based on the flexible feature of potassium channel turrets, a good starting rKir1.1 channel structure was modeled for the accessibility of rKir1.1 channel turrets to TPNQ toxin. In combination with experimental alanine scanning mutagenesis data, computational approaches were further used to obtain a reasonable TPNQ toxin-rKir1.1 channel complex structure, which was completely different from the known binding modes between animal toxins and potassium channels. TPNQ toxin mainly adopted its helical domain as the channel-interacting surface together with His12 as the pore-blocking residue. The important Gln13 residue mainly contacted channel residues near the selectivity filter, and Lys20 residue was surrounded by a polar "groove" formed by Arg118, Thr119, Glu123, and Asn124 in the channel turret. On the other hand, four turrets of rKir1.1 channel gathered to form a narrow pore entryway for TPNQ toxin recognition. The Phe146 and Phe148 residues in the channel pore region formed strong hydrophobic protrusions, and produced dominant nonpolar interactions with toxin residues. These specific structure features of rKir1.1 channel vestibule well matched the binding of potent TPNQ toxin, and likely restricted the binding of the classical animal toxins. The TPNQ toxin-rKir1.1 channel complex structure not only revealed their unique interaction mechanism, but also would highlight the diverse animal toxin-potassium channel interactions, and elucidate the relative insensitivity of rKir1.1 channel towards animal toxins.


Relationship between SIRT1 gene and adolescent depressive disorder with nonsuicidal self-injury behavior: Based on gene methylation and mRNA expression.
The incidence of non-suicidal self-injury (NSSI) behavior in adolescents is increasing year by year. Patients with a history of both depression and NSSI behavior tend to be at greater risk for suicide. At present, the mechanism of adolescent depressive disorder with NSSI behavior is not clear and still in research and exploration. The expression of the Silent Information Regulator 2 Related Enzyme 1 (SIRT1) gene is closely related to the level of serotonin in molecular mechanisms, and may be closely related to the occurrence and development of depressive disorder. This study aimed to explore the relationship between the SIRT1 gene and NSSI behaviors in adolescents with depressive disorder. A total of 15 adolescent depressed patients with NSSI behavior and 15 healthy controls were enrolled in the study. Bisulfite Sequencing PCR (BSP) was used to test the methylation level of SIRT1 gene promoter region of the participants. The real-time fluorescent quantitative PCR was conducted to measure the mRNA expression level of SIRT1 gene. Our study found that the methylation level of SIRT1 gene promoter region at cytosine-guanine dinucleotide 5 (CpG5) site in depression group was higher than that of control group. Compared with that of control group, the plasma concentration of Sirt1 protein significantly decreased in depression group. Our study investigated the methylation level and the mRNA expression of SIRT1 gene in adolescent depressive patients with NSSI behavior. The study points towards finding an in vivo molecular marker for those adolescent patients.


[Leptospirosis in the Province of Santa Fé, Argentina. Epidemiologic, clinical and socioeconomic description].
Leptospirosis is produced by a bacteria belonging to the Leptospira genus. Water contaminated with this germ which comes from the urine of infected animals is an excellent source of infection for mammals. It gets into the human body through the skin or mucus. The aims of this work were to describe the cases that occurred during the first five months of 2001, and to determine the causes of this phenomenon. There was a total of 49 patients confirmed by the laboratory, 39 of whom completed the epidemiologic form; 24 of whom were over 15 years of age, 19 were male cases, 13 of whom involved in semiurban jobs; 82% presented fever, 74.3% headaches: 71.8% mialgias and 48.7% presented the conjunctivitis shot; 61.5% showed a flu syndrome, 20.5% a meningeal, and 18.5% respiratory and renal syndrome. These patients had a low level of education, with unstable jobs and lots of rodents in or near their houses. The structure of these houses was precarious, with a deficient system of water drainage. Fifty percent of the patients had primary instruction, 11.1% secondary instruction, one was illiterate, and none had gone to university. Patients coming from rural areas (an outbreak), belonged to a higher social and economic condition and had got infected through exposure in relation with their jobs. Sources of infection in the rural patients were different from those of the urban patients: in the former they were related to the presence of rodents, which related to the type of work, while in the urban cases they had to do with the poverty of their living conditions.


Keratoconus onset after age 50.
To describe the sudden clinical manifestations of keratoconus in a 51-year-old woman. The patient had stable annual refractions for several years with 0.50 diopters (D) astigmatism in each eye and later developed 2.00 and 6.00 D of astigmatism in the right and left eyes, respectively. Topography and tomography showed definite keratoconus in the left eye and possible keratoconus in the right eye. The patient had no known family history of keratoconus and no known connective tissue disease other than fibromyalgia. She wore soft contacts for 20 years and had allergies, but did not rub her eyes. The patient was treated with corneal collagen cross-linking (CXL). Although rare, ectatic changes can occur later in life without prior surgery or trauma. The patient has shown early signs of improvement with CXL despite her age.


Estrogen immunosuppression is regulated through estrogenic responses in the thymus.
Previous studies have clearly established that physiologic and pharmacologic levels of estrogens modulate immunologic responses that result in simultaneous activation of the reticuloendothelial system and depression of cell-mediated immunity. The mechanisms of estrogen immunoregulation were examined in adult female mice administered pharmacologic levels of exogenous estrogens. Evaluation of steroidal and nonsteroidal compounds with varying degrees of estrogenicity (i.e., uterotrophic activity) provided evidence that their immunotoxicity, for the most part, correlates with estrogenicity. The mechanisms responsible for these effects appear to be complex, mediated through a direct chemical interaction with lymphoid target cells, as well as with nonlymphoid tissue, resulting in the release of soluble immunoregulatory factors. The latter phenomenon was examined in detail and it appears to constitute a regulatory factor(s) produced by thymic epithelium in response to an estrogen stimulus. This response is not only estrogen specific but may involve specific binding to estrogen receptors or receptor-like structures present in cytosol preparations from thymic epithelial cells.


Treatment Strategies and Prognostic Factors of 2018 FIGO Stage IIIC Cervical Cancer: A Review.
Cervical cancer is the fourth most common malignant tumor globally in terms of morbidity and mortality. The presence of lymph node metastasis (LNM) is an independent prognostic factor for progression-free survival (PFS) and overall survival (OS) in cervical cancer patients. The International Federation of Gynecology and Obstetrics (FIGO) staging system was revised in 2018. An important revision designates patients with regional LNM as stage IIIC, pelvic LNM only as stage IIIC1, and para-aortic LNM as stage IIIC2. However, the current staging system is only based on the anatomical location of metastatic lymph nodes (LNs). It does not consider other LN status parameters, which may limit its prognostic significance to a certain extent and needs further exploration and confirmation in the future. The purpose of this review is to summarize the choice of treatment for stage IIIC cervical cancer and the effect of different LN status parameters on prognosis.


Why does society accept a higher risk for alcohol than for other voluntary or involuntary risks?
Societies tend to accept much higher risks for voluntary behaviours, those based on individual decisions (for example, to smoke, to consume alcohol, or to ski), than for involuntary exposure such as exposure to risks in soil, drinking water or air. In high-income societies, an acceptable risk to those voluntarily engaging in a risky behaviour seems to be about one death in 1,000 on a lifetime basis. However, drinking more than 20 g pure alcohol per day over an adult lifetime exceeds a threshold of one in 100 deaths, based on a calculation from World Health Organization data of the odds in six European countries of dying from alcohol-attributable causes at different levels of drinking. The voluntary mortality risk of alcohol consumption exceeds the risks of other lifestyle risk factors. In addition, evidence shows that the involuntary risks resulting from customary alcohol consumption far exceed the acceptable threshold for other involuntary risks (such as those established by the World Health Organization or national environmental agencies), and would be judged as not acceptable. Alcohol's exceptional status reflects vagaries of history, which have so far resulted in alcohol being exempted from key food legislation (no labelling of ingredients and nutritional information) and from international conventions governing all other psychoactive substances (both legal and illegal). This is along with special treatment of alcohol in the public health field, in part reflecting overestimation of its beneficial effect on ischaemic disease when consumed in moderation. A much higher mortality risk from alcohol than from other risk factors is currently accepted by high income countries.


KSHV G protein-coupled receptor inhibits lytic gene transcription in primary-effusion lymphoma cells via p21-mediated inhibition of Cdk2.
Kaposi sarcoma (KS) remains the most common AIDS-associated malignancy worldwide. In sub-Saharan Africa especially, this aggressive endothelial-cell tumor is a cause of widespread morbidity and mortality. Infection with Kaposi sarcoma-associated herpesvirus (KSHV) is now known to be an etiologic force behind KS and primary-effusion lymphoma (PEL). Over time, KSHV has pirated many human genes whose products regulate angiogenesis, inflammation, and the cell cycle. One of these, the KSHV vGPCR, is a lytic product that is a constitutively active homolog of the IL-8 receptor. Although it is considered a viral oncogene and causes KS-like lesions in mice, vGPCR expression results in cell-cycle arrest of KSHV-infected PEL cells. In the present study, we show that this arrest is mediated by p21 in a p53-independent manner; the resulting Cdk2 inhibition decreases the efficiency of chemical induction of KSHV lytic transcripts ORF 50 and 26. Importantly, Cdk2 activity is also essential for replication in other human herpesviruses. The ability of vGPCR to delay or abort KSHV replication may explain how despite being a lytic product, this potent signaling molecule has a vital role in tumor formation via its induction of various KS-associated cytokines.


LogMAR and Stereoacuity in Keratoconus Corrected with Spectacles and Rigid Gas-permeable Contact Lenses.
This study showed an improvement in three-dimensional depth perception of subjects with bilateral and unilateral keratoconus with rigid gas-permeable (RGP) contact lens wear, relative to spectacles. This novel information will aid clinicians to consider RGP contact lenses as a management modality in keratoconic patients complaining of depth-related difficulties with their spectacles. The aim of this study was to systematically compare changes in logMAR acuity and stereoacuity from best-corrected spherocylindrical spectacles to RGP contact lenses in bilateral and unilateral keratoconus vis-à-vis age-matched control subjects. Monocular and binocular logMAR acuity and random-dot stereoacuity were determined in subjects with bilateral (n = 30; 18 to 24 years) and unilateral (n = 10; 18 to 24 years) keratoconus and 20 control subjects using standard psychophysical protocols. Median (25th to 75th interquartile range) monocular (right eye) and binocular logMAR acuity and stereoacuity improved significantly from spectacles to RGP contact lenses in the bilateral keratoconus cohort (P < .001). Only monocular logMAR acuity of affected eye and stereoacuity improved from spectacles to RGP contact lenses in the unilateral keratoconus cohort (P < .001). There was no significant change in the binocular logMAR acuity from spectacles to RGP contact lenses in the unilateral keratoconus cohort. The magnitude of improvement in binocular logMAR acuity and stereoacuity was also greater for the bilateral compared with the unilateral keratoconus cohort. All outcome measures of cases with RGP contact lenses remained poorer than control subjects (P < .001). Binocular resolution and stereoacuity improve from spectacles to RGP contact lenses in bilateral keratoconus, whereas only stereoacuity improves from spectacles to RGP contact lenses in unilateral keratoconus. The magnitude of improvement in visual performance is greater for the binocular compared with the unilateral keratoconus cohort.


A new approach to the design of information systems for foodservice management in health care facilities.
An organizational framework for integrating foodservice data into an information system for management decision making is presented. The framework involves the application to foodservice of principles developed by the disciplines of managerial economics and accounting, mathematics, computer science, and information systems. The first step is to conceptualize a foodservice system from an input-output perspective, in which inputs are units of resources available to managers and outputs are servings of menu items. Next, methods of full cost accounting, from the management accounting literature, are suggested as a mechanism for developing and assigning costs of using resources within a foodservice operation. Then matrix multiplication is used to illustrate types of information that matrix data structures could make available for management planning and control when combined with a conversational mode of computer programming.


Seven-day administration of recombinant human granulocyte colony-stimulating factor to newborn rats: modulation of neonatal neutrophilia, myelopoiesis, and group B Streptococcus sepsis.
Single-pulse administration of rhG-colony-stimulating factor (CSF) to neonatal rats was previously demonstrated to induce peripheral neutrophilia and modulate bone marrow (BM) neutrophil storage and proliferative pools (NSP + NPP). In this study, we investigated the prolonged effects of 7 days of rhG-CSF therapy (5 micrograms/kg/per day). Sprague-Dawley newborn rats (less than or equal to 24 hours) were injected intraperitoneally (IP) (daily for 7 days) with rhG-CSF or phosphate-buffered saline/human serum albumin (PBS/HSA). RhG-CSF induced a significant early and late peripheral neutrophilia: 6,905 +/- 1,625 (day 1) and 9,223 +/- 515 microL (day 7) v 1,275 +/- 90/microL (P less than or equal to .0001). In addition, 7 days of rhG-CSF resulted in a significant increase in the BM NSP: 3,247 +/- 190/microL v 1,677 +/- 339/microL (P less than or equal to .001). There was, however, no depletion or significant change in the BM NPP. Seven days of rhG-CSF also induced a mild increase in BM CFU-GM colony formation (P less than or equal to .01). There was, however, no significant change in liver/spleen CFU-GM colonies or in the CFU-GM proliferative rate in either the BM or liver/spleen cultures. Finally, 7 days of prophylactic rhG-CSF therapy resulted in a synergistic response with antibiotic therapy and significantly modulated the mortality rate during experimental group B streptococcal sepsis (GBS) (100% v 50%) (GvsC) (P less than or equal to .001). Pulse rhG-CSF administered at 6 hours or 18 hours after GBS inoculation, however, failed to act synergistically with antibiotics to improve survival or prevent peripheral neutropenia. This study suggests that 7 days of prophylactic rhG-CSF therapy induces peripheral neutrophilia, myeloid maturation, increases neutrophil BM reserves and also may provide immunologic enhancement of neonatal host defense during experimental GBS in term neonatal rats.