Qualitative and quantitative analysis of some synthetic, chemically acting laxatives in urine by gas chromatography-mass spectrometry.
A method for the qualitative and quantitative simultaneous analysis of dioxyanthraquinone, desacetyl-Bisacodyl, phenolphthalein and Oxyphenisatin in human urine using gas chromatography-mass spectrometry (GC-MS) has been developed. The compounds were extracted from urine at pH 7.5 with diethyl ether using Extrelut extraction columns, followed by evaporation and trimethylsilylation. The method used electron beam ionization GC-MS employing a computer-controlled multiple-ion detector (mass fragmentography). The recovery from urine for the various compounds was between 80% and 100%. The detection limit for these compounds was in the range 0.01--0.05 micrograms/ml of urine. The method proved to be suitable for measuring urine concentrations for at least four days after administration of a single oral low therapeutic dose of the laxatives to sixteen healthy volunteers.


Validation of two automatic devices: Omron HEM-7252G-HP and Omron HEM-7251G for self-measurement of blood pressure according to the European Society of Hypertension International Protocol revision 2010.
The aim of this study was to validate the performance of Omron HEM-7252G-HP and Omron HEM-7251G for monitoring upper arm blood pressure (BP) in accordance with the European Society of Hypertension International Protocol revision 2010 (ESH-IP revision 2010). Three trained medical doctors validated the performance of these devices by comparing data obtained from these devices with those obtained using a standard mercury sphygmomanometer. We included 33 participants (19 men and 14 women for the experiment using HEM-7252G-HP; 16 men and 17 women for the experiment using HEM-7251G). The mean age of the participants was 50±12 and 53±10 years in the respective studies. The percentages of test device-observer mercury sphygmomanometer BP differences within 5, 10, and 15 mmHg were 76, 92, and 97% for systolic BP (SBP) and 83, 97, and 99% for diastolic BP (DBP), respectively, in the Omron HEM-7252G-HP and 77, 92, and 99% for SBP and 85, 94, and 98% for DBP, respectively, in the Omron HEM-7251G in the part 1 analysis; both SBP and DBP passed the part 1 and part 2 criteria.The mean differences between the device and mercury readings for SBP and DBP were as follows: HEM-7252G-HP, -1.5±5.1 and -1.2±3.9 mmHg, respectively; HEM-7351G, -0.6±4.7 and -0.2±4.4 mmHg, respectively. The Omron HEM-7252G-HP and HEM-7251G passed all the requirements of the ESH-IP 2010 revision.


A bi-radial approach to define the sagittal geometry of the healthy ankle.
Previous descriptions of the sagittal geometry of the tibia and talus have involved single radius curves. The purpose of this investigation was to: determine if the sagittal curvature of the medial and lateral sides of the talus and tibia can be described by dividing the condyles into anterior and posterior regions, determine tibiotalar congruency, and categorize the morphological configurations of the talus and tibia. Eighteen subjects underwent weightbearing CT scans and the osseous curvature was analyzed. For the talus, the medial anterior radius was smaller than the lateral anterior radius. For the distal tibia, the lateral posterior radius was smaller than the medial posterior radius. Tibiotalar congruency varied by region. The most common geometric configuration was two cones, one anterior and one posterior, pointed in opposite directions. The sagittal profiles of the tibia and talus can be more accurately described using a bi-radial approach as compared to a single radius.


Mechanism of drug release from polymethacrylate-based extrudates and milled strands prepared by hot-melt extrusion.
The aim of the study was the formulation of solid dispersions of the poorly water-soluble drug celecoxib and a polymethacrylate carrier by hot-melt extrusion. The objectives were to elucidate the mechanism of drug release from obtained extrudates and milled strands addicted to the solid-state properties of the solid dispersions and to examine and eliminate stability problems occurring under storage, exposure of mechanical stress, and in vitro dissolution. Transparent extrudates containing up to 60% drug could be prepared with a temperature setting below the melting point of celecoxib. XRPD and DSC measurements indicated the formation of a glassy solid solution, where the drug is molecularly dispersed in the carrier. The amorphous state of the glassy solid solution could be maintained during the exposure of mechanical stress in a milling process, and was stable under storage for at least 6 months. Solid-state properties and SEM images of extrudates after dissolution indicated a carrier-controlled dissolution, whereby the drug is molecularly dispersed within the concentrated carrier layer. The glassy solid solution showed a 58-fold supersaturation in 0.1 N HCl within the first 10 min, which was followed by a recrystallization process. Recrystallization could be inhibited by an external addition of HPMC.


Enteropathogens and Rotavirus Vaccine Immunogenicity in a Cluster Randomized Trial of Improved Water, Sanitation and Hygiene in Rural Zimbabwe.
Oral rotavirus vaccines (RVVs) are less efficacious in low-income versus high-income settings, plausibly due to more enteropathogen exposure through poor water, sanitation and hygiene (WASH). We explored associations between enteropathogens and RVV immunogenicity and evaluated the effect of improved WASH on enteropathogen carriage. We detected stool enteropathogens using quantitative molecular methods and measured anti-rotavirus immunoglobulin A by enzyme-linked immunosorbent assay in infants enrolled to a cluster randomized 2 × 2 factorial trial of improved WASH and improved infant feeding in Zimbabwe (NCT01824940). We used multivariable regression to explore associations between enteropathogens and RVV seroconversion, seropositivity and geometric mean titer. We evaluated effects of improved WASH on enteropathogen prevalence using linear and binomial regression models with generalized estimating equations. Among 224 infants with enteropathogen and immunogenicity data, 107 (47.8%) had ≥1 pathogen and 39 (17.4%) had ≥2 pathogens detected at median age 41 days (interquartile range: 35-54). RVV seroconversion was low (23.7%). After adjusting for Sabin-poliovirus quantity, pan-enterovirus quantity was positively associated with RVV seroconversion (relative risk 1.61 per 10-fold increase in pan-enterovirus; 95% confidence interval: 1.35-1.91); in the same model, Sabin quantity was negatively associated with RVV seroconversion (relative risk: 0.76; 95% confidence interval: 0.60-0.96). There were otherwise no meaningful associations between individual or total pathogens (bacteria, viruses, parasites or all pathogens) and any measure of RVV immunogenicity. Enteropathogen detection did not differ between randomized WASH and non-WASH groups. Enteropathogen infections were common around the time of rotavirus vaccination in rural Zimbabwean infants but did not explain poor RVV immunogenicity and were not reduced by a package of household-level WASH interventions.


Measuring magnesium, calcium and potassium isotope ratios using ICP-QMS with an octopole collision cell in tracer studies of nutrient uptake and translocation in plants.
The ability of a quadrupole-based ICP-MS with an octopole collision cell to obtain precise and accurate measurements of isotope ratios of magnesium, calcium and potassium was evaluated. Hydrogen and helium were used as collision/reaction gases for ICP-MS isotope ratio measurements of calcium and potassium in order to avoid isobaric interference with the analyte ions from (mainly) argon ions 40Ar+ and argon hydride ions 40Ar1H+. Mass discrimination factors determined for the isotope ratios 25Mg/24Mg, 40Ca/44Ca and 39K/41K under optimized experimental conditions varied between 0.044 and 0.075. The measurement precisions for 25Mg/24Mg, 40Ca/44Ca and 39K/41K were found to be 0.09%, 0.43% and 1.4%, respectively. This analytical method that uses ICP-QMS with a collision cell to obtain isotope ratio measurements of magnesium, calcium and potassium was used in routine mode to characterize biological samples (nutrient solution and small amounts of digested plant samples). The mass spectrometric technique was employed to study the dynamics of nutrient uptake and translocation in barley plants at different root temperatures (10 degrees C and 20 degrees C) using enriched stable isotopes (25Mg, 44Ca and 41K) as tracers. For instance, the mass spectrometric results of tracer experiments demonstrated enhanced 25Mg and 44Ca uptake and translocation into shoots at a root temperature of 20 degrees C 24 h after isotope spiking. In contrast, results obtained from 41K tracer experiments showed the highest 41K contents in plants spiked at a root temperature of 10 degrees C.


Metformin ameliorates Ox-LDL-induced foam cell formation in raw264.7 cells by promoting ABCG-1 mediated cholesterol efflux.
The accumulation of lipids in macrophages contributes to the development of atherosclerosis. Cholesterol efflux of lipid-loaded macrophages mediated by ATP binding cassette (ABC) cholesterol transporters, on the other hand, has been shown to attenuate atherosclerosis progression in patients with unknown mechanism. We therefore sought to test the effect of metformin that reduced cardiovascular risk in diabetic patients independent of its hypoglycemia effect on cholesterol transport in murine raw264.7 macrophages. Mouse raw264.7 macrophages were loaded with Ox-LDL (50 μg/ml) for 24 h before incubated with metformin (15 μM) for 24 h. Foam cell formation was assessed by Oil red staining and BIODIPY fluorescent staining as well as cholesterol-ester quantification by commercial kit. Cholesterol uptake and expression of scavenger receptors were detected by flow-cytometry. Cholesterol efflux capacity was measured by fluorescent plate-reader and ABC transporters were detected by Western Blots. Cytokines were detected by ELISA in supernatants and normalized by cellular lysates. Our results showed that metformin decreased oxidized low-density lipoprotein (Ox-LDL)-induced cholesterol accumulation and foam cell formation by increasing cholesterol efflux to HDL, which was associated with an upregulation of ABC transporter ABCG-1. Moreover, metformin increased Ox-LDL-impaired IL-10 secretion, an important anti-foam cell cytokine in atherosclerosis. Our data highlighted the therapeutic potential of targeting macrophage cholesterol efflux with new or existing drugs for the possible reduction of foam cell formation in the prevention and treatment of diabetes-accelerated atherosclerosis.


Preoperative prediction of the lymphovascular tumor thrombus of colorectal cancer with the iodine concentrations from dual-energy spectral CT.
The aim of this study was to explore application value of iodine concentration from dual-energy spectral computed tomography (DESCT) in preoperative prediction of lymphovascular tumor thrombus in patients with colorectal cancer (CRC). We finally retrospectively analyzed 50 patients with CRC who underwent abdominal DESCT before receiving any preoperative treatment and underwent surgery to obtain pathological specimens which were stained with hematoxylin-eosin (HE) staining. According to the presence of cancer cell nests in blood vessels and lymphatic vessels, the subjects were divided into the positive group and negative group of lymphovascular tumor thrombus. Two radiologists independently measured the normalized iodine concentration (NIC) values, effective atomic number (Zeff) and CT values of virtual monochromatic images (VMIs) at 40-90 keV of the primary tumors in the arterial phase (AP) and venous phase (VP). Used SPSS 17.0 to calculate the receiver operating characteristic (ROC) curve to evaluate diagnostic value. The patients were divided into lymphovascular tumor thrombus positive group(n = 16) and negative group(n = 34). The values of NIC-AP and NIC-VP in the positive group were 0.17 ± 0.09, 0.51 ± 0.13, respectively. And those in the negative group were 0.15 ± 0.06, 0.43 ± 0.12, respectively. There was significant difference in NIC-VP value between the two groups (p = 0.039), but there was no significant difference in NIC-AP value (p = 0.423). The optimal threshold value of NIC-VP value for diagnosis of lymphovascular tumor thrombus was 0.364. The sensitivity was 68.8% and the specificity was 67.6%. The NIC-VP value of DESCT can be used to predict the presence or absence of the lymphovascular tumor thrombus in CRC patients before operation, which is helpful to select the best treatment scheme and evaluate its prognosis.


A PHYSICAL THERAPIST WHO SWEARS: A CASE SERIES.
Swearing deserves attention in the physical therapy setting due to its potential positive psychological, physiological, and social effects. The purpose of this case series is to describe 2 cases in which a physical therapist swears in the clinical setting and its effect on therapeutic alliance. Case 1 is a 19-year-old male treated for a hamstring strain, and case 2 is a 23-year-old male treated post-operatively for anterior cruciate ligament reconstruction. The physical therapist utilized social swearing in the clinic with the goal of motivating the patient and enhancing the social connection with the patient, to improve therapeutic alliance. The patient in case 1 reported a decrease in therapeutic alliance after the physical therapist began swearing during physical therapy treatments, whereas the patient in case 2 reported an increase in therapeutic alliance. Both patients disagreed that physical therapist swearing is unprofessional and disagreed that swearing is offensive, and both patients agreed physical therapists should be able to swear around their patients. Physical therapist swearing may have positive and negative influences in the clinic setting and may not be considered unprofessional. These are, to our knowledge, the first published cases of a physical therapist swearing in the clinical setting.


Proportion of pet cats registered with a veterinary practice and factors influencing registration in the UK.
Registration of a cat with a veterinary practice is likely to be a critical factor for access to key preventative medicine. A cross-sectional study was conducted to collect data in the United Kingdom on the registration status of cats and potential explanatory variables. These data were also used to identify potential sources of bias associated with selecting controls from veterinary registered populations of cats due to differences between registered and unregistered cats. Cat owners reported that 13.6% (84/616) of their cats had not been registered with a veterinary practice since living at their current address. Multivariable logistic regression indicated that unregistered cats were significantly more likely than registered cats to be entire, to have not been vaccinated within the previous year, to be living in households in Northern Ireland and in households with an annual income <£10,000.(1) Whilst the neuter status and the vaccination status of the cat are likely to result from non-registration, the household location and annual income are factors that can be used to inform future interventions designed to increase the proportion of veterinary registered cats.


Smallpox vaccination techniques; from knives and forks to needles and pins.
Factors affecting the development of smallpox vaccination techniques are discussed and 11 different techniques for inoculating the vaccine are identified and described. The earliest, the simple cut or scratch, was already widely used for smallpox inoculation (variolation). Later, when it became evident that Jenner's claim of lifelong protection was not being achieved parallel, cross-hatched and rotatory methods which produced more severe reactions were introduced, often at more than one site. These methods were then discontinued and even prohibited in some countries, when improved vaccine quality resulted in excessively-severe reactions with such techniques. They were replaced by improved methods such as multiple pressure and multiple puncture with the bifurcated needle, both of which were used extensively. However, the simple scratch method remained popular until the end of the vaccination era. Although the instruments used are not discussed in detail, representative examples of the wide variety used at various times and for the various techniques are illustrated. Again, the simplest and earliest designs remained in use throughout.


Dense transcript profiling in single cells by image correlation decoding.
Sequential barcoded fluorescent in situ hybridization (seqFISH) allows large numbers of molecular species to be accurately detected in single cells, but multiplexing is limited by the density of barcoded objects. We present correlation FISH (corrFISH), a method to resolve dense temporal barcodes in sequential hybridization experiments. Using corrFISH, we quantified highly expressed ribosomal protein genes in single cultured cells and mouse thymus sections, revealing cell-type-specific gene expression.


Heart-on-a-chip platforms and biosensor integration for disease modeling and phenotypic drug screening.
Heart disease is the leading cause of death worldwide and imposes a significant burden on healthcare systems globally. A major hurdle to the development of more effective therapeutics is the reliance on animal models that fail to faithfully recapitulate human pathophysiology. The predictivity of in vitro models that lack the complexity of in vivo tissue remain poor as well. To combat these issues, researchers are developing organ-on-a-chip models of the heart that leverage the use of human induced pluripotent stem cell-derived cardiomyocytes in combination with novel platforms engineered to better recapitulate tissue- and organ-level physiology. The integration of novel biosensors into these platforms is also a critical step in the development of these models, as they allow for increased throughput, real-time and longitudinal phenotypic assessment, and improved efficiency during preclinical disease modeling and drug screening studies. These platforms hold great promise for both improving our understanding of heart disease as well as for screening potential therapeutics based on clinically relevant endpoints with better predictivity of clinical outcomes. In this review, we describe state-of-the-art heart-on-a-chip platforms, the integration of novel biosensors into these models for real-time and continual monitoring of tissue-level physiology, as well as their use for modeling heart disease and drug screening applications. We also discuss future perspectives and further advances required to enable clinical trials-on-a-chip and next-generation precision medicine platforms.


Chemosensory-Related Gene Family Members of the Horn Fly, Haematobia irritans irritans (Diptera: Muscidae), Identified by Transcriptome Analysis.
Horn flies are one of the most significant economic pests of cattle in the United States and worldwide. Chemical control methods have been routinely utilized to reduce populations of this pest, but the steady development of insecticide resistance has prompted evaluation of alternative control strategies. Behavior modifying compounds from natural products have shown some success in impacting horn fly populations, and a more thorough understanding of the horn fly chemosensory system would enable improvements in the development of species-specific compounds. Using an RNA-seq approach, we assembled a transcriptome representing genes expressed in adult female and male horn fly head appendages (antennae, maxillary palps, and proboscides) and adult fly bodies from which heads were removed. Differential gene expression analysis identified chemosensory gene family members that were enriched in head appendage tissues compared with headless bodies. Candidate members included 43 odorant binding proteins (OBP) and 5 chemosensory binding proteins (CSP), as well as 44 odorant receptors (OR), 27 gustatory receptors (GR), and 34 ionotropic receptors (IR). Sex-biased expression of these genes was not observed. These findings provide a resource to enable future studies targeting horn fly chemosensation as part of an integrated strategy to control this blood-feeding pest.


A Simple Approach for Minimally Invasive Combined Aortic and Mitral Valve Surgery.
There is now extension of minimally invasive techniques to involve concomitantly aortic and mitral valves through a single small incision. We share our experience in such surgeries through upper partial sternotomy with approaching the mitral valve through the dome of the left atrium. Two matched groups of cases receiving concomitant aortic and mitral valve surgeries are compared regarding the surgical outcomes: the minimally invasive group (group A) including 72 patients and the conventional group (group B) including 78 patients. The mean age was 52 ± 8 years in group A and 53 ± 7 years in group B. Males represented (42%) in group A and (49%) in group B. The mean mechanical ventilation time was significantly shorter in group A (4.3 ± 1.2 hours) than in group B (6.1 ± 0.8 hours) with a p-value of 0.001. In addition, the amount of chest tube drainage and the need for blood transfusion units were significantly less in group A (250 ± 160 cm3 and 1.3 ± 0.8 units, respectively) when compared with group B (320 ± 180 cm3 and 1.8 ± 0.9 units, respectively) with p-values of 0.013 and 0.005, respectively. Over a follow-up period of 3.2 ± 1.1 years, one mortality occurred in each group with no significant difference (p-value = 0.512). Combined aortic and mitral valve surgery through upper partial sternotomy with approaching the mitral valve through the dome of the left atrium is safe and effective with the advantages of less postoperative blood loss, need for blood transfusion, and mechanical ventilation time compared with conventional aortic and mitral valve surgery.


Mechanisms of coxsackievirus B5 mediated beta-cell death depend on the multiplicity of infection.
Coxsackievirus infections may trigger and accelerate pancreatic beta-cell death, leading to type I diabetes. Unrestricted coxsackievirus B5 replication in cultured beta-cells inoculated with high multiplicity leads to rapid lytic cell death. Evidence from other virus-host cell systems indicates that host cell responses to infection may depend on the multiplicity of infection (MOI). Thus, the aim of this study was to compare the mechanisms of beta-cell death during high versus low multiplicity of coxsackievirus B5 infection. Cultures of highly differentiated mouse insulinoma cells and primary adult human islets were infected with coxsackievirus B5 at multiplicities of >1,000 or <0.5 TCID50 per cell. The results of nuclear morphology and viability stainings, TUNEL staining and electrophoretic DNA fragmentation analysis showed high multiplicity infection to predominantly induce necrosis and transient apoptosis. In low multiplicity culture, however, necrosis was only moderately induced and apoptosis increased steadily with time. This was best demonstrated by a tenfold higher apoptosis/necrosis ratio than after high multiplicity inoculation. Expression of gamma-glutamyl cysteine synthetase increased in both infective cultures but the level of intracellular glutathione permanently depleted only at high multiplicity and recovered fully at low multiplicity. Thus, apoptosis represents an important mechanism of beta-cell death after low multiplicity of coxsackievirus B5 infection. This process is associated with maintenance of a physiological intracellular glutathione profile differing dramatically from the high multiplicity infection during which necrosis dominates and intracellular thiol balance deteriorates. These data suggest that the pattern and mechanisms of coxsackievirus B5 infection induced beta-cell death depend on the MOI.


Translation termination is involved in histone mRNA degradation when DNA replication is inhibited.
The levels of replication-dependent histone mRNAs are coordinately regulated with DNA synthesis. A major regulatory step in histone mRNA metabolism is regulation of the half-life of histone mRNAs. Replication-dependent histone mRNAs are the only metazoan mRNAs that are not polyadenylated. Instead, they end with a conserved stem-loop structure, which is recognized by the stem-loop binding protein (SLBP). SLBP is required for histone mRNA processing, as well as translation. We show here, using histone mRNAs whose translation can be regulated by the iron response element, that histone mRNAs need to be actively translated for their rapid degradation following the inhibition of DNA synthesis. We also demonstrate the requirement for translation using a mutant SLBP which is inactive in translation. Histone mRNAs are not rapidly degraded when DNA synthesis is inhibited or at the end of S phase in cells expressing this mutant SLBP. Replication-dependent histone mRNAs have very short 3' untranslated regions, with the stem-loop located 30 to 70 nucleotides downstream of the translation termination codon. We show here that the stability of histone mRNAs can be modified by altering the position of the stem-loop, thereby changing the distance from the translation termination codon.


Short-term efficacy of angiotensin receptor-neprilysin inhibitor treatment in patients with ST-segment elevation myocardial infarction with reduced ejection fraction after primary percutaneous coronary intervention: a propensity score matching study.
Acute myocardial infarction (AMI) causes a series of pathophysiological changes, including myocardial necrosis, myocardial edema, and microvascular damage. These changes eventually lead to severe cardiovascular events, such as ventricular remodeling, heart failure, and papillary dysfunction. Impaired cardiac function after ST-segment elevation myocardial infarction (STEMI) often manifests as a decrease in left ventricular ejection fraction (LVEF). Clinical trials have shown that angiotensin receptor-neprilysin inhibitor (ARNI) treatment has the potential to improve LVEF in patients with STEMI after primary percutaneous coronary intervention (PPCI). The purpose of this study was to evaluate the short-term efficacy of ARNI versus angiotensin-converting enzyme inhibitor (ACEI) treatment in patients with STEMI who exhibit reduced LVEF after PPCI. A total of 169 patients with STEMI exhibiting post-PPCI LVEF below 50% who were orally treated with ARNI between December 2017 and August 2020 were selected as the experimental group. A total of 136 patients with STEMI exhibiting post-PPCI LVEF below 50% who were orally treated with an ACEI between January 2016 and August 2020 were selected as the control group. LVEF was measured using cardiac ultrasonography during hospitalization and 3 months after discharge. Linear and logistic regression analyses were performed to compare patient demographics and hospitalization variables to evaluate the risk factors for change and rate of improvement in LVEF. Propensity score matching (PSM) was used to account for confounding factors. After PSM, the study cohort consisted of 81 patients in the ARNI group and 123 in the ACEI group. After an average follow-up period of 3 months, no significant difference was noted in the LVEF improvement rate between the experimental and control groups (P = 0.475, 95% CI: -0.062 to 0.134). Multivariate logistic regression analysis also indicated no significant correlation between the change in LVEF and oral ARNI treatment in patients with STEMI exhibiting reduced LVEF after PPCI (P > 0.05). The short-term effect of ARNI treatment on the cardiac function of patients with STEMI and reduced LVEF after PPCI is not superior to that of ACEI treatment.


Antitumour Organometallics. III. In Vivo Activity of Diphenylantimony(III) and Diorganotin(IV) Dithiophosphorus Derivatives Against P388 Leukemia.
Diphenylantimony(III) and diorganotin(IV) derivatives of dithiophosphorus ligands, i.e. Ph(2)SbS(2)PR'(2) (R' = Ph, OPr-i) and R(2)Sn(S(2)PR'(2))(2) (R = n-Bu, Ph, R' = Ph; R = Ph, R' = OPr-i), have been screened against P388 leukemia in mice. All the compounds showed marginal activity towards this tumor system, some of them increasing the life span of the animals with more than 20%. The best results were obtained with (di-iso-propylphosphorodithioato)diphenylantimony(III) which exhibited a T/C value of 136%, at a dose of 5 mg/kg, administered on days 1,2 and 3 after tumor transplantation.


Duodenal-Jejunal bypass improves glucose homeostasis in association with decreased proinflammatory response and activation of JNK in the liver and adipose tissue in a T2DM rat model.
There is accumulating evidence that obesity leads to a proinflammatory state, which plays crucial roles in insulin resistance and development of type 2 diabetes mellitus (T2DM). Previous studies demonstrated that weight loss after bariatric surgery was accompanied by a suppression of the proinflammatory state. However, the effect of bariatric surgery on the proinflammatory state and associated signaling beyond weight loss is still elusive. The objective of this study was to investigate the effect of duodenal-jejunal bypass (DJB) on glucose homeostasis, the proinflammatory state and the involving signaling independently of weight loss. A high-fat diet and low-dose streptozotocin administration were used to induce T2DM in male Sprague-Dawley rats. The diabetic rats underwent DJB or sham surgery. The blood glucose, glucose tolerance and insulin resistance were determined to evaluate the glucose homeostasis. Serum insulin, GLP-1 and hsCRP were detected by ELISA. The gene expression of TNF-α, IL-6, IL-1β and MCP-1 in liver and fat was determined by quantitative real-time RT-PCR. The JNK activity and serine phosphorylation of IRS-1 in liver and adipose tissue were determined by Western blotting. Compared to the S-DJB group, DJB induced significant and sustained glycemic control with improved insulin sensitivity and glucose tolerance independently of weight loss. DJB improved the proinflammatory state indicated by decreased circulating hsCRP and proinflammatory gene expression in the liver and adipose tissue. The JNK activity and serine phosphorylation of IRS-1 in liver and adipose tissue were significantly reduced after DJB. DJB achieved a rapid and sustainable glycemic control independently of weight loss. The data indicated that the improved proinflammatory state and decreased JNK activity after DJB may contribute to the improved glucose homeostasis.


Well-Being Tracking via Smartphone-Measured Activity and Sleep: Cohort Study.
Automatically tracking mental well-being could facilitate personalization of treatments for mood disorders such as depression and bipolar disorder. Smartphones present a novel and ubiquitous opportunity to track individuals' behavior and may be useful for inferring and automatically monitoring mental well-being. The aim of this study was to assess the extent to which activity and sleep tracking with a smartphone can be used for monitoring individuals' mental well-being. A cohort of 106 individuals was recruited to install an app on their smartphone that would track their well-being with daily surveys and track their behavior with activity inferences from their phone's accelerometer data. Of the participants recruited, 53 had sufficient data to infer activity and sleep measures. For this subset of individuals, we related measures of activity and sleep to the individuals' well-being and used these measures to predict their well-being. We found that smartphone-measured approximations for daily physical activity were positively correlated with both mood (P=.004) and perceived energy level (P<.001). Sleep duration was positively correlated with mood (P=.02) but not energy. Our measure for sleep disturbance was not found to be significantly related to either mood or energy, which could imply too much noise in the measurement. Models predicting the well-being measures from the activity and sleep measures were found to be significantly better than naive baselines (P<.01), despite modest overall improvements. Measures of activity and sleep inferred from smartphone activity were strongly related to and somewhat predictive of participants' well-being. Whereas the improvement over naive models was modest, it reaffirms the importance of considering physical activity and sleep for predicting mood and for making automatic mood monitoring a reality.


Pacemakers in young patients: 1977.
Recent experience with implanted cardiac pacemakers in nine young patients is reported. Advance in technology include improved pacemaker generator design and placement, and improved lead design and placement. No patients died; our only complication, failure to capture, required repositioning of the lead. All pacemaker replacements were elective. This series helps to define the more favorable current prognosis for the young patient needing pacemaker therapy.


Competence requirements in intensive and critical care nursing--still in need of definition? A Delphi study.
Empirical studies in competence are lacking in the field of intensive and critical care nursing. To identify competence requirements, by soliciting the views of intensive care unit nurses and physicians. Two rounds of the Delphi method were used in 2006 in Finland. Data were analysed by content analysis and with descriptive statistics. Competence requirements in intensive and critical care nursing can be divided into five main domains: knowledge base, skill base, attitude and value base, nursing experience base and personal base of the nurse. Four of these domains can be found in the existing requirements and one new domain - personal base of the nurse - was identified. Competence requirements are multidimensional. Earlier descriptions of competence are not sufficient; more comprehensive and cohesive descriptions are needed. The personal base of a nurse should also be included in the competence requirements in intensive and critical care nursing.


Overproduction and secretion of α-ketoglutaric acid by microorganisms.
This mini-review presents a summary of research results of biotechnological production of alpha-ketoglutaric acid (KGA) by bacteria and yeasts. KGA is of particular industrial interest due to its broad application scope, e.g., as building block chemical for the chemical synthesis of heterocycles, dietary supplement, component of infusion solutions and wound healing compounds, or as main component of new elastomers with a wide range of interesting mechanical and chemical properties. Currently KGA is produced via different chemical pathways, which have a lot of disadvantages. As an alternative several bacteria and yeasts have already been studied for their ability to produce KGA as well as for conditions of overproduction and secretion of this intermediate of the tricarboxylic acid cycle. The aim of this mini-review was to summarize the known data and to discuss the potentials of biotechnological processes of KGA production.


Effect of pain reduction on postural sway, proprioception, and quadriceps strength in subjects with knee osteoarthritis.
To investigate whether alleviation of knee pain influences quadriceps function, proprioceptive acuity, and postural stability in patients with knee osteoarthritis (OA). A crossover, within-subject, double blind study design involving 68 subjects with painful knee OA. Each subject received an intra-articular injection into one or both knees (both if symptomatic) of either 5 ml 0.5% bupivacaine or 5 ml 0.9% saline. Two weeks later they received an injection of the alternative agent. Subjects and observer were unaware of the order of injection, which was randomly assigned. Knee pain (100 mm visual analogue scale), static postural sway, knee proprioceptive acuity, maximum voluntary contraction (MVC), and percentage activation of the quadriceps were assessed immediately before and one hour after each injection. Significant pain reduction was achieved one hour post-bupivacaine (mean difference as a percentage change 56.85, 95% CI 31.01 to 73.65; p<0.001) and post-saline (mean difference as a percentage change 41.94, 95% CI 11.57 to 76.66; p< 0.001), with no significant difference between the two. Both MVC and activation increased significantly post-bupivacaine (mean percentage differences 18.83, 95% CI -31.79 to -0.26, and -11.90, 95% CI -39.53 to 2.97, respectively; both p<0.001) and post-saline (mean percentage differences -7.64, 95% CI -21.96 to 4.73, and -10.71, 95% CI -25.19 to 2.60 respectively; both p<0.001). Proprioception worsened after bupivacaine (mean percentage difference -28.15%, 95% CI -83.47 to 19.74; p=0.009), but there was no effect on postural sway; saline injection had no effects. There was no order effect, and comparison of median percentage changes showed no significant differences between injections for change in MVC, activation, proprioception, or sway. Reduction in knee pain through either peripheral (local anaesthetic) or central (placebo) mechanisms resulted in increased MVC. This increase, however, did not result in improvements in proprioception or static postural stability, suggesting that other mechanisms play a part in these functions, at least in this acute model.


Does contingency awareness mediate the influence of emotional learning on the cueing of visual attention?
Previous research has indicated that conditioning depends on contingency awareness (CA). However, we argue that these studies have examined this issue under methodological conditions that might be insensitive to associative learning without CA. In the present study we examined the effect of an experimental manipulation of CA on attentive processing of classically conditioned stimuli, which is sensitive to associative learning with and without CA. We found that aversive conditioning with additional contingency instructions modulated visual attention, in the sense that the conditioned cues captured and held attention more strongly than the non-conditioned cues. Surprisingly, conditioning under conditions of restricted CA yielded a response pattern that was different from that under full CA. These findings suggest that conditioning with full and restricted CA can lead to qualitatively different effects on attention.


The effect of peroxynitrite on sphincter of Oddi motility.
Nitric oxide (NO*) is an inhibitory neurotransmitter that induces sphincter of Oddi relaxation. Superoxide (O*-2)-scavenging enzymes are present in enteric plexuses of the sphincter of Oddi and O*-2 alters sphincter of Oddi motor function. O*-2 rapidly oxidizes nitric oxide (NO*) to form peroxynitrite (ONOO-), thus terminating the biological activity of NO*. The aim of our study was to determine the effects of ONOO- on sphincter of Oddi motility in vitro. Adult opossums were sacrificed and the sphincter of Oddi was removed and placed in a tissue bath containing oxygenated Krebs solution at 37 degreesC. In the first series of experiments, force transducers recorded tension in a transverse orientation at two sites along the spontaneously contracting sphincter of Oddi. In a second series of experiments, circular muscle strips were precontracted with carbachol and stimulated by an electrical field. ONOO-, superoxide dismutase (SOD), Nomega-nitro-l-arginine (l-NNA), or oxyhemoglobin were added to the tissue baths. ONOO- decreased the frequency of contractions in the spontaneously contracting sphincter of Oddi. Adding hemoglobin increased the frequency of contractions. ONOO- also increased the stimulation-induced relaxation compared to controls. The increase in relaxation induced by ONOO- was inhibited by oxyhemoglobin and l-NNA but not SOD. Pretreatment with oxyhemoglobin prevented the increase in the stimulation-induced relaxation caused by ONOO-. These results suggest that hemoglobin binds ONOO- or that ONOO- generates NO.


Rectocele repair by anterolateral rectopexy: long-term functional outcome.
Rectoceles are frequently associated with feelings of pelvic discomfort and symptoms of obstructed defaecation (OD). Repair by a transvaginal or transanal approach might result in de novo dyspareunia in up to approximately 40% of the cases. This study was designed to investigate whether anterolateral rectopexy provides an adequate rectocele repair without dyspareunia as a side effect. A consecutive series of 33 women (median age 55 years; range: 37-73) with a symptomatic rectocele (depth > 3 cm) underwent anterolateral rectopexy. Before the operation, all patients underwent evacuation proctography (EP), which was repeated 6 months after the repair in all but three patients. A standardized questionnaire concerning pelvic discomfort, OD and dyspareunia was used to assess the long-term effect of rectocele repair. The response rate was 91%. Six months after the procedure, EP revealed a recurrent or persistent rectocele in six patients (20%). However, in four of these six patients, the depth of the rectocele was < 3 cm. The median duration of follow-up was 74 months (range: 2-96). Among the patients with an adequate repair, signs of OD persisted in 55%. None of the patients encountered de novo dyspareunia after the procedure. Anterolateral rectopexy provides an effective tool for anatomical correction of rectoceles and does not result in dyspareunia as a side effect. However, despite adequate repair, OD persist in the majority of patients.


Light from heat lamps affects sow behaviour and piglet salivary melatonin levels.
The light environment regulates animal physiology and behaviour. As widely used supplementary heat sources in creep areas, the effect of visible light radiated by infrared heat lamps on pigs is worth investigating. To investigate the effects of light from heat lamps on the behaviour of sows and piglets and possible endocrine mechanisms, 24 primiparous sows were randomly assigned to three supplementary heat source treatments: (1) 250 W non-luminous ceramic heat lamps (CE, n = 8), (2) 175 W red heat lamps (RL, n = 8), and (3) 175 W transparent heat lamps (TL, n = 8). All heat lamps were turned off on Day 15 postpartum. Piglets were weighed on days 3 and 21 postpartum. The number and duration of suckling within 24 h were analysed via video recordings on days 4, 8, and 16 postpartum. Sow posture changes during the day and night were detected using the YOLOv4 target detection network model. One marked piglet from six litters randomly selected from each treatment was used for saliva collection. Saliva samples were collected at 0800, 1400, 2000, and 0200 (+1 d) on days 10 and 20 postpartum. The results showed that the mean postural change frequency of TL sows was higher than that of CE sows (P < 0.05), while that of RL sows was not different from that of CE and TL sows. However, the duration of the sows being in each posture was not affected by the treatment. The total suckling duration of TL piglets was significantly longer than that of CE piglets, but there was no significant difference in the performance of the piglets. The melatonin concentrations in the saliva of piglets at 10 and 20 days of age in the three treatments showed different diurnal rhythms, but there was no significant difference in the levels of melatonin in TL piglets between night and day. Differences in salivary cortisol levels only appeared between the CE and RL groups at 20 days of age. Based on the present results, the illuminance and spectrum of the transparent heat lamps were sufficient to stimulate sow activity and inhibit melatonin levels in piglets. However, the stimulating effect on suckling was not sufficient to significantly improve the performance of piglets. Exposure to red heat lamps, rather than ceramic lamps, resulted in the strongest circadian rhythm of salivary melatonin in piglets.


Readily available fluorescein isothiocyanate-conjugated antibodies can be easily converted into targeted phototoxic agents for antibacterial, antiviral, and anticancer therapy.
Fluorescein-labeled antibodies have little, if any, photodynamic effect because energy acquired by light absorption is rapidly dissipated in fluorescence. However, they can be easily and efficiently converted to selective photodynamic sensitizers by iodination under mild conditions. We have outlined general experimental procedures that can be used to turn a fluorescein-labeled anti-Escherichia coli antibody into a photodynamic sensitizer that selectively kills E. coli while sparing closely related Salmonella typhimurium. These results demonstrate that iodination did not destroy the specificity or activity of the antibody. This technique should be applicable to the large number of fluoresceinated antibodies that are commercially available. Thus, this strategy provides a simple way to rapidly prepare a large number of targeted phototoxic agents that can be used for the selective destruction with light of nearly any type of tissue or organism.


Habitual sleep duration predicts caloric and macronutrient intake during sleep deprivation.
Our modern society has created two tightly linked epidemics: insufficient sleep and obesity. Although laboratory studies have established that sleep loss is associated with increased caloric intake, the critical question of how habitual at-home sleep duration influences total caloric and macronutrient intake during subsequent total sleep deprivation remains largely unexplored. At-home sleep patterns were monitored via wrist actigraphy for at least one week before a 29-h in-laboratory total sleep deprivation (TSD) session (N = 45). Participants had ad-libitum access to food, which was measured at 6-h intervals throughout the in-laboratory session. Short habitual sleep duration was significantly associated with increased caloric and macronutrient intake during the last 6 h of TSD (06:00-12:00). Short habitual sleep increases the risk for morning overeating after acute sleep deprivation. Early identification and behavioral intervention of those at risk of overeating may help reduce the likelihood of long-term health consequences.


[Larvae of barnacles (Cirripedia: Thoracica) in the White sea plankton].
The barnacle fauna in the White Sea is briefly described. The morphology of barnacle larvae in this water body is comparatively analyzed. The characters important for the larvae identification are given particular attention. A classification key was developed for the nauplius and cyprid larvae of barnacles in the White Sea.


ROR1/STAT3 positive feedback loop facilitates cartilage degeneration in Osteoarthritis through activation of NF-κB signaling pathway.
Osteoarthritis (OA) is a chronic joint disorder with a serious impact on society. The main pathological change in OA is articular cartilage degeneration, which is directly associated with imbalance of anabolic and catabolic activities in chondrocytes. To evaluate the expression and biological effects of ROR1 in OA cartilage and determine whether knockdown of ROR1 attenuates cartilage degeneration. ROR1 expression in OA clinical specimens was evaluated by western blotting and immunohistochemistry. The effects of ROR1 on anabolic and catabolic activities were evaluated in Wnt5a-treated human primary chondrocytes by western blotting, immunofluorescence, and luciferase assay. The effects of ROR1 knockdown on cartilage degeneration in a surgical OA mouse model were examined by X-ray imaging and Safranin O-Fast Green histological staining. ROR1 was considerably upregulated in cartilage tissues of OA patients. ROR1 knockdown alleviated the activation of the NF-κB signaling pathway and reversed the suppression of collagen II and aggrecan by Wnt5a, as well as upregulation of ADAMTS-5 and MMP-13 in chondrocytes. In addition, ROR1 knockdown significantly reduced Wnt5a-induced STAT3 nuclear translocation. STAT3 binding to the ROR1 promoter indicated a positive feedback loop between ROR1 and STAT3. ROR1 knockdown was confirmed to dramatically alleviate cartilage degradation in the DMM induced-OA mouse model. Increased expression of ROR1 in OA cartilage tissues leads to a positive feedback loop with STAT3, which activates the NF-κB signaling pathway, resulting in an imbalance between chondrocyte anabolism and catabolism. These results indicate a potential new therapeutic target for the treatment of OA.


Impact on Life Expectancy of Withdrawing Thiopurines in Patients with Crohn's Disease in Sustained Clinical Remission: A Lifetime Risk-Benefit Analysis.
Long-term treatment with thiopurines is associated with a decreased risk of Crohn's disease (CD) flare but an increased risk of various cancers depending on gender, age, and presence of extensive colitis. We evaluated risks and benefits of withdrawing thiopurines in patients with CD in prolonged remission. We developed a Markov model assessing risks and benefits of withdrawing thiopurines compared to continuing thiopurines in a lifetime horizon. The model was stratified by age (35 and 65 years old at thiopurine withdrawal), gender and presence of extensive colitis. Parameter estimates were taken from French cohorts and hospital databases, cancer and death national registries and published literature. Life expectancy, rates of relapse, serious adverse events, and causes-of-death were evaluated. In patients without extensive colitis, continuing thiopurines increased life expectancy up to 0.03 years for 35 year-old men and women but decreased life expectancy down to 0.07 years for 65 year-old men and women. Withdrawal strategy became the preferred strategy at 40.6 years for men, and 45.7 years for women without extensive colitis. In patients with extensive colitis, continuation strategy was the preferred strategy regardless of age. Risk-benefit analysis was not modified by duration of CD activity. Factors determining life expectancy associated with withdrawal or continuation of thiopurines in patients with CD and in sustained clinical remission vary substantially according to gender, age and presence of extensive colitis. Individual decisions to continue or withdraw thiopurines in patients with CD in sustained remission should take into account these parameters.


At home parent-administered dressing changes in paediatric burns aftercare: A survey of burns centres?" practice.
Following paediatric burn injury, dressings are initially changed in outpatient clinics, necessitating regular visits with substantial burden for parents, children and services. This can potentially be lessened if some parents go on to administer dressing changes for their child at home. However, a lack of data regarding support for parent-administered dressing changes is present. The aim of this study was to describe current practice and views regarding at-home parent-administered dressing changes (PAD) in the UK. An online survey was distributed to 20 paediatric burns services in England and Wales. The survey used fixed and free-text responses to collect data on whether PAD is offered and the reasons for this; patient and parent eligibility criteria; training and support; and respondents?" views on the advantages and disadvantages of PAD. Analysis comprised simple descriptive statistics and simple content analysis of free-text responses. Thirteen responses were received (response rate = 65%). Eleven respondents indicated their service offers PAD. Two respondents reported their service does not offer PAD due to alternative nurse outreach appointments (n = 1), and service resource limitations (n = 1), though another respondent indicated service cost savings. Twelve respondents regard PAD positively (n = 8) or very positively (n = 4). Most respondents reported that 10% or fewer parents refuse PAD when offered (n = 7). Perceived advantages of PAD included reduced travel burden (n = 9), patient better able to cope with dressing changes (n = 8), better school and work attendance for child and parent respectively (n = 6), and reduced financial impact on families (n = 4). No formal eligibility criteria for PAD are extant, though 5 respondents described informal criteria in place in their service, predominantly involving dressing frequency (n = 5), and size or complexity of wound (n = 4). The survey indicates that most paediatric burns services support PAD. However, the absence of formal eligibility criteria, and informal criteria open to interpretation, risks inequity of support received by children and their families. Further research should evaluate whether this inequity extends to variable clinical outcomes to determine what works for who and under what circumstances when supporting parents in paediatric burns aftercare.


Aortoiliac segment examination with colour flow Duplex--a pilot study using Klean Prep. to improve the image quality.
Currently colour flow Duplex examination of the iliac arteries is at best 84-92% sensitive. In an attempt to find a technique to improve on this sensitivity we have studied the effect of Klean Prep, an iso-osmotic bowel preparation, on the Duplex image and Doppler signal obtained when scanning iliac arteries. Twenty iliac segments in 10 arteriopaths were scanned by a blinded observer, after either starving for 12 h or having Klean Prep bowel preparation. Grey scale image, colour mapping and Doppler signal to noise ratios were scored on a linear analogue system. Each patient was subsequently rescanned after the other method of preparation and was once again scored by a blinded observer. The two sets of scores were then compared. We found significant improvements in the linear analogue scoring of grey scale images, colour mapping and Doppler signal to noise ratios, when using Klean Prep as opposed to starving the patient prescan. Preparing patients with Klean Prep before iliac Duplex examination improves the visualisation of these arteries.


Two-dimensional strain fields on the cross-section of the bovine humeral head under contact loading.
The objective of this study was to provide a detailed experimental assessment of the two-dimensional cartilage strain distribution on the cross-section of immature and mature bovine humeral heads subjected to contact loading at a relatively rapid physiological loading rate. Six immature and six mature humeral head specimens were loaded against glass and strains were measured at the end of a 5s loading ramp on the textured articular cross-section using digital image correlation analysis. The primary findings indicate that elevated tensile and compressive strains occur near the articular surface, around the center of the contact region. Few qualitative or quantitative differences were observed between mature and immature joints. Under an average contact stress of approximately 1.7 MPa, the peak compressive strains averaged -0.131+/-0.048, which was significantly less than the relative change in cartilage thickness, -0.104+/-0.032 (p<0.05). The peak tensile strains were significantly smaller in magnitude, at 0.0325+/-0.013. These experimental findings differ from a previous finite element analysis of articular contact, which predicted peak strains at the cartilage-bone interface even when accounting for the porous-hydrated nature of the tissue, its depth-dependent inhomogeneity, and the disparity between its tensile and compressive properties. These experimental results yield new insights into the local mechanical environment of the tissue and cells, and suggest that further refinements are needed in the modeling of contacting articular layers.


Low Socioeconomic Status Is Associated with Worse Outcomes After Curative Surgery for Colorectal Cancer: Results from a Large, Multicenter Study.
Socioeconomic status (SES) has been associated with early mortality in cancer patients. However, the association between SES and outcome in colorectal cancer patients is largely unknown. The aim of this study was to investigate whether SES is associated with short- and long-term outcome in patients undergoing curative surgery for colorectal cancer. Patients who underwent curative surgery in the region of Rotterdam for stage I-III colorectal cancer between January 2007 and July 2014 were included. Gross household income and survival status were obtained from a national registry provided by Statistics Netherlands Centraal Bureau voor de Statistiek. Patients were assigned percentiles according to the national income distribution. Logistic regression and Cox proportional hazard regression were performed to assess the association of SES with 30-day postoperative complications, overall survival and cancer-specific survival, adjusted for known prognosticators. For 965 of the 975 eligible patients (99%), gross household income could be retrieved. Patients with a lower SES more often had diabetes, more often underwent an open surgical procedure, and had more comorbidities. In addition, patients with a lower SES were less likely to receive (neo) adjuvant treatment. Lower SES was independently associated with an increased risk of postoperative complications (Odds ratio per percent increase 0.99, 95%CI 0.99-0.998, p = 0.004) and lower cancer-specific mortality (Hazard ratio per percent increase 0.99, 95%CI 0.98-0.99, p = 0.009). This study shows that lower SES is associated with increased risk of postoperative complications, and poor cancer-specific survival in patients undergoing surgery for stage I-III colorectal cancer after correcting for known prognosticators.


Myths and realities of the 80-hour work week.
Myths are so ingrained into cultural traditions that emotion frequently overshadows a rational evaluation of the facts. The reduction in resident work hours has resulted in the formation of several myths. The purpose of this review is to examine the published data on resident work hours to separate out myth from reality. An electronic database was searched for publications related to resident training, work-hours, continuity of care, sleep deprivation, quality of life, patient safety, clinical/operative experience, faculty work hours, and surgical education. Sleep deprivation has been shown to be harmful, and residents played a role in advocating for work-hour limits. Surgical residents have seen a less dramatic improvement in quality of life compared with other disciplines. Work-hour reductions have decreased participation in clinic but have not resulted in a significant decline in clinical or operative exposure. Limiting resident work hours will unlikely result in a decrease health-care cost. Reduction in resident work hours has not resulted in an improvement or deterioration in patient outcome. Reduction of work hours has not increased faculty work hours nor made surgery a more attractive career choice. Despite strongly held opinions, resident work-hour reduction has resulted in little significant change in lifestyle, clinical exposure, patient well-being, faculty work hours, or medical student recruitment.


Air Medical Support for a Peripheral Hospital in Southern Israel: An Evolving Role for the Air Ambulance and Emergency Department Clinicians.
The early use of helicopters on the battlefields of Korea and Vietnam led to the introduction of "air ambulances" into civilian practice. Initially, these aircraft were tasked to retrieve casualties and provide conventional paramedic care at the scene and en route to the hospital. The introduction of advanced medical teams on helicopters led to the evolution of helicopter emergency medical service units. Yoseftal Hospital is a 65-bed hospital serving the town of Eilat in southern Israel. It does not offer full intensive care or specialist services but does provide general surgical, medical, pediatric, and psychiatric services. The hospital is 100 km from the nearest tertiary center in Be'er Sheva, an ambulance journey of 2 hours across desert. The hospital serves a population of 70,000 residents and up to 500,000 tourists. Recognizing the need to provide a facility to transfer critical or complex patients, in August 2021, the Israeli Ministry of Health provided a dedicated helicopter to Yoseftal Hospital. The first 100 missions are presented. Forty-four missions were for cardiac presentations. For patients with ST-segment elevation myocardial infarction, the median time from the initial medical contact at Yoseftal to reception at the tertiary center was 141 minutes. Other transfers were for ear, nose, and throat (2); neurosurgical (14); trauma (9); respiratory (6); obstetrics and gynecology (3); and pediatric services (14) and nontraumatic surgical emergencies (15). Our experience validates the need for this resource and highlights the importance of robust clinical, operational, and transfer protocols between Yoseftal and the receiving specialist units. The challenging and diverse clinical activity requires additional skills and competencies for the critical care paramedics on the aircraft. Integrating the flight crew into the emergency department team facilitated early activation of the aircraft and expedited patient preparation for flight. Our experience describes an evolving new role for the helicopter-support for a remote peripheral hospital.


[Could speech rate of Wilson's disease dysarthric patient be improved in dual task condition?].
Dysarthria is one of the first sign of neurological Wilson's disease and is often characterized by a decreased speech rate. The aim of this study is to determine the abilities of Wilson's disease dysarthric patients to control their speech rate. We examined the impact of dual-tasking on the speech rate of patients as compared to healthy control speakers and in relation with their ability to accelerate speech rate when instructed to do so. Twenty-six patients and twenty-six age- and sex-matched healthy controls repeated a sentence during 20 seconds at a comfortable speech rate used as reference. They were then asked to perform the same repetition task but in dual task conditions, in which sentence repetition was done while performing three types of executive grapho-motor tasks. Finally, the ability to control speech rate was tested by asking the speakers to perform the sentence repetition task alone but at a fast rate of speech. A significantly slower speech rate was observed for all patients as compared to controls. In the dual-task conditions, while the speech rate of healthy speakers accelerated significantly, two behaviors are found for the patients. Forty-two percent of the patients reproduced the control pattern with a significant increased in speech rate, while the other group significantly decreased their speech rate. Comparison of the ability of the two groups to intentionally modulate speech rate, when instructed to accelerate, shows that significantly better acceleration was achieved by speakers in the former group compared with the latter. This study supports the finding that patients with Wilson's disease exhibit an impaired speech rate and also impaired control of speech rate. Indirect assessment of speech rate modulation with the help of a dual-task paradigm has proven to be useful to distinguish patient behaviors. This paradigm could also be envisioned as a tool for rehabilitation.


Comparison of Emergency Department Use Between Pregnant People With and Without Disabilities in Ontario, Canada.
Emergency department (ED) use in pregnancy is common and occurs for a variety of reasons, including obstetrical complications, exacerbated underlying conditions, and inadequate outpatient health care access. People with disabilities have elevated rates of certain medical, psychiatric, and obstetrical conditions as well as inadequate access to prenatal care; their risk of ED use in pregnancy is not known, however. To compare the risk of ED use in pregnancy among people with physical, sensory, and intellectual or developmental disabilities with those without disabilities. Population-based cohort study leveraging linked administrative health data sets in Ontario, Canada, April 2003 to March 2019. Analysis included all recognized pregnancies to people with a preexisting physical, sensory, intellectual or developmental, or 2 or more (multiple) disabilities, and those without a disability. Data were analyzed from May 2022 to January 2023. Disability was ascertained using algorithms applied to 2 or more outpatient physician visits or 1 or more ED visits or hospitalizations before conception. Modified Poisson regression-generated adjusted relative risks (aRR) and 95% CIs for any ED visit in pregnancy, from the estimated conception date up to the end of the pregnancy, adjusted for age, parity, income quintile, rurality, immigrant status, and preexisting chronic conditions, mental illness, and substance use disorders. The cohort included 2 659 895 pregnant people with physical (221 739 participants; mean [SD] age, 29.8 [6.1] years), sensory (71 891 participants; mean [SD] age, 29.1 [6.4] years), intellectual or developmental (3877 participants; mean [SD] age, 26.1 [6.7] years), and multiple disabilities (14 359 participants; mean [SD] age, 29.5 [6.5] years), and pregnant people without a disability (2 348 023 participants; mean [SD] age, 29.4 [5.9] years). The rate of ED visits in pregnancy was 25.4% in people without a disability (596 771 visits). Relative to these individuals, the aRR for ED use was elevated in people with physical (aRR, 1.26; 95% CI, 1.25-1.27), sensory (aRR, 1.15; 95% CI, 1.14-1.17), intellectual or developmental (aRR, 1.33; 95% CI, 1.28-1.38), and multiple disabilities (aRR, 1.43; 95% CI, 1.40-1.46). In this population-based study, people with disabilities were at elevated risk of ED use in pregnancy. This finding underscores the need for research on the benefits of proactive strategies to manage preexisting conditions in these individuals, improve their access to outpatient obstetrical and medical care, and prepare them for when ED visits occur.


Use of Remifentanil for Open in utero Fetal Myelomeningocele Repair Maintains Uterine Relaxation with Reduced Volatile Anesthetic Concentration.
Open fetal repair of myelomeningocele (MMC) is an option for prenatally diagnosed spina bifida. Historically, high-dose volatile anesthetic was used for uterine relaxation but is associated with fetal cardiovascular depression. We examined the impact of administering a supplemental remifentanil infusion on the concentration of inhaled anesthetic required for intraoperative uterine relaxation. We retrospectively analyzed 22 consecutive patients who underwent open fetal MMC repair with desflurane anesthesia from 2014 to 2018. The anesthetic protocol was modified to include high-dose opioid with remifentanil in 2016. We examined intraoperative end-tidal desflurane concentrations, vasopressor use, incidence of umbilical artery Doppler abnormalities, and incidence of preterm labor and delivery. Patients (n = 11) who received desflurane and remifentanil (Des/Remi) were compared to patients (n = 11) who received desflurane (Des) alone. Intraoperatively, the maximum end-tidal desflurane required to maintain uterine relaxation was lower in the Des/Remi group (7.9 ± 2.2% vs. 13.1 ± 1.2%, p < 0.001). The mean phenylephrine infusion rate was also lower in the Des/Remi group (36 ± 14 vs. 53 ± 10 mcg/min, p = 0.004). Use of opioid with supplemental remifentanil was associated with lower volatile anesthetic dosing and decreased vasopressor use; fetal outcomes were not different. Remifentanil may allow for less volatile anesthetic use while maintaining adequate uterine relaxation.


Dengue, chikungunya … and the missing entity - Zika fever: A new emerging threat.
Zika virus (ZIKV), a relative newcomer from the flavivirus group that includes dengue, Japanese encepahalitis and yellow fever, is one of the emerging pathogens that is fast transcending geographical boundaries. It is a vector-borne disease transmitted by the same Aedes aegypti and Aedes albopictus, which cause dengue and chikungunya. In addition to the vector-mediated transmission of Zika fever, probable human-to-human transmission through exchange of body fluids, including sexual and perinatal transmission and through blood transfusion, makes containment of this new entity more challenging. Moreover, a high index of suspicion by an astute physician is necessary for diagnosis of Zika fever in view of the similarity of symptoms with dengue and chikungunya, especially in areas, where these two diseases are already endemic. Zika, till recently, has had minimal impact, but its true potential is unfolding with increasing detection of congenital malformities, Guillain-Barré syndrome and other neurological and autoimmune syndromes in patients with recent history of ZIKV infection, or when mothers get infected with Zika during first or second trimester of pregnancy. The association, however, needs to be established, nonetheless it is important that we keep a close vigil on this emerging vector borne disease - the 'ZIKA' fever.


Chemo-photodynamic therapy with light-triggered disassembly of theranostic nanoplatform in combination with checkpoint blockade for immunotherapy of hepatocellular carcinoma.
Hepatocellular carcinoma (HCC) is a common malignant tumor with high rate of metastasis and recurrence. Although immune checkpoint blockade (ICB) has emerged as a promising type of immunotherapy in advanced HCC, treatment with ICB alone achieves an objective remission rate less than 20%. Thus, combination therapy strategies is needed to improve the treatment response rate and therapeutic effect. A light-triggered disassembly of nanoplatform (TB/PTX@RTK) co-loaded an aggregation induced emission (AIE) photosensitizer (TB) and paclitaxel (PTX) was prepared for on-command drug release and synergistic chemo-photodynamic therapy (chemo-PDT). Nano-micelles were characterized for drug loading content, hydrodynamic size, absorption and emission spectra, reactive oxygen species production, and PTX release from micelles. The targeted fluorescence imaging of TB/PTX@RTK micelles and the synergistic anti-tumor efficacy of TB/PTX@RTK micelles-mediated chemo-PDT combined with anti-PD-L1 were assessed both in vitro and in vivo. The TB/PTX@RTK micelles could specifically accumulate at the tumor site through cRGD-mediated active target and facilitate image-guided PDT for tumor ablation. Once irradiated by light, the AIE photosensitizer of TB could produce ROS for PDT, and the thioketal linker could be cleaved by ROS to precise release of PTX in tumor cells. Chemo-PDT could not only synergistically inhibit tumor growth, but also induce immunogenic cell death and elicit anti-tumor immune response. Meanwhile, chemo-PDT significantly upregulated the expression of PD-L1 on tumor cell surface which could efficiently synergize with anti-PD-L1 monoclonal antibodies to induce an abscopal effect, and establish long-term immunological memory to inhibit tumor relapse and metastasis. Our results suggest that the combination of TB/PTX@RTK micelle-mediated chemo-PDT with anti-PD-L1 monoclonal antibodies can synergistically enhance systemic anti-tumor effects, and provide a novel insight into the development of new nanomedicine with precise controlled release and multimodal therapy to enhance the therapeutic efficacy of HCC.


Increased VLCFA-lipids and ELOVL4 underlie neurodegeneration in frontotemporal dementia.
Rare, yet biologically critical, lipids that contain very long chain fatty acids (VLCFA-lipids) are synthesized in the brain by the enzyme ELOVL4. High levels of VLCFA-lipids are toxic to cells and excess VLCFA-lipids are actively removed by ABCD1 in an ATP-dependent manner. Virtually nothing is known about the impact of VLCFA-lipids in neurodegenerative diseases. Here, we investigated the possible role of VLCFA-lipids in frontotemporal dementia (FTD), which is a leading cause of younger-onset dementia. Using quantitative discovery lipidomics, we identified three VLCFA-lipid species that were significantly increased in FTD brain compared to controls, with strong correlations with ELOVL4. Increases in ELOVL4 expression correlated with significant decreases in the membrane-bound synaptophysin in FTD brain. Furthermore, increases in ABCD1 expression correlated with increases in VLCFA-lipids. We uncovered a new pathomechanism that is pertinent to understanding the pathogenesis of FTD.


How phonological and orthographic decoding complicates the simple view of reading in Chinese: examining mediation through listening comprehension.
Advocates of the science of reading have invoked the simple view of reading (SVR) to justify an approach that foregrounds decoding in early reading instruction. SVR describes reading comprehension as the product of decoding and listening comprehension. The current study examined the complexity of the SVR, focusing on the phonological and orthographic decoding in third-grade readers of Chinese. One hundred and forty-three students participated in this study. The measures included phonological decoding (pinyin invented spelling), orthographic decoding, listening comprehension and reading comprehension. Drawing upon regression analyses and multivariate path models, the study found that phonological decoding at both segmental and suprasegmental processing significantly predicted Chinese reading comprehension, yet a more significant effect of orthographic decoding surfaced. And the best-fitting model suggested listening comprehension was better characterized as a mediator rather than a covariance with decoding component in the decoding-reading relation when orthographic decoding was incorporated into decoding component to evaluate the validity of the SVR in Chinese. The results imply that orthographic decoding is a legitimate decoding component and that the two decoding constructs alone are insufficient for higher-level reading ability (reading comprehension) since the contribution appears to be mediated through the path route of oral language capacity (indexed by listening comprehension). This enriches the current understanding of the SVR in non-alphabetic languages and indicates that decoding training on both phonological and orthographic dimension should be highlighted in early Chinese reading instruction.


Fetal immune response to oral pathogens and risk of preterm birth.
The purpose of this study was to determine the relationship between fetal inflammatory and immune responses to oral pathogens and risk for preterm birth. Six hundred and forty umbilical cord blood specimens were prospectively collected. Cord serum levels of C-reactive protein, interleukin (IL)-1beta, IL-6, tumor necrosis factor (TNF)-alpha, Prostaglandin E2, and 8-isoprostane were determined by enzyme-linked immunosorbent assay and categorized as > median (high) versus < or = median (low). Presence of fetal immunoglobulin M (IgM) antibody against oral pathogens was determined by checkerboard immunoblot assay; detection of > or = 1 oral pathogen specific antibody was categorized as positive. Preterm birth was defined as spontaneous delivery at <35 weeks. Chi-square analysis was used to determine association between cord serum mediator or IgM category and preterm birth. Odds ratios (OR) for preterm birth were calculated, stratified by mediator and IgM category. Of 640 births, 48 (7.5%) delivered preterm. Preterm birth rates were higher if categorized as high versus low 8-isoprostane or TNF-alpha (23 vs 5%, P < .001 and 10 vs 4%, P < .01, respectively). Preterm birth rates were also higher if categorized as IgM positive versus negative (10.6 vs 5.8%, P = .04). The joint effects of fetal IgM seropositivity, detectable C-reactive protein, or high 8-isoprostane, PGE(2), or TNF-alpha resulted in significantly increased risk for preterm birth (adjusted OR [95% CI]: 6.0 [2.2-16.5], 4.3 [1.6-11.5], 4.1 [1.5-11.6], and 7.6 [2.3-20.8], respectively). Fetal exposure to oral pathogens evidenced by an IgM response is associated with preterm birth, and the risk for preterm birth is greatest among fetuses that also demonstrate an inflammatory response.


Neuropathology.
The surgical neuropathologist who examines corticectomy specimens from infants and children with epilepsy is in a unique position to make observations of fundamental importance in understanding the pathogenesis of seizures as well as the basic neurobiology of brain lesions that are associated with epilepsy. Findings on the resected human tissue using novel immunocytochemical and molecular probes can supplement and even build on relevant findings in experimental models, the goal of which is an understanding of epilepsy at cellular and subcellular levels.


Placental/umbilical cord blood: experience of st. Eugenio Hospital collection center.
Umbilical cord blood (UCB) contains stem cells and may be an alternative source to bone marrow and peripheral blood stem cells for allogeneic transplantation for the treatment of hematologic malignancies and genetic disorders. Many UCB banks have been established worldwide to quickly provide high quality materials for transplantation. Moreover, a detailed set of standards for cord blood banking have been drawn to guarantee the quality of the products. The aim of this study was to analyze our activity between 1998 and 2001, seeking to improve the number of suitable UCB units. Written informed consent was obtained from healthy women with an uncomplicated pregnancy. During the study period, we collected 1060 UCB units; 328 (31%) were banked, whereas 732 (69%) were discarded. The collections were performed in 73% vaginal deliveries and 27% of cesarean sections. The main reason for the exclusion was biological; in fact, a low number of nucleated cells and a low volume accounted for 71% of the total discarded units. Moreover, 20% of the units were discarded because of parental clinical reasons. Our study shows that maternal history must be completely reviewed before labor and obstetrical factors should be considered to improve the number of UCB units.


Structural effects of proline substitution and metal binding on hexameric cyclic peptoids.
L-Proline and N-methoxyethyl glycine have been included in novel cyclic hexameric peptoids. Supramolecular coordination with Na(+) triggered the formation of the first 1D metal-organic framework based on peptoids.


Productivity costs decrease after endoscopic sinus surgery for refractory chronic rhinosinusitis.
The primary objective of this pilot study was to define the change in productivity costs following endoscopic sinus surgery (ESS) for chronic rhinosinusitis (CRS). Secondary objectives were to identify CRS-related characteristics that may influence the degree of productivity improvement after ESS. Prospective, multi-institutional, observational cohort study. The human capital approach was used to define productivity costs. Annual absenteeism, presenteeism, and lost leisure time were quantified to define annual lost productive time (LPT). LPT was monetized using the annual daily wage rates obtained from the 2012 US Census and the 2013 US Department of Labor statistics. Twenty-seven patients with refractory CRS who underwent ESS were followed for a mean of 15 months (range, 8-25 months). Following ESS, there were improvements in annual absenteeism (22 days reduced to 3 days), annual presenteeism (41 days reduced to 19 days), and annual household days lost (12 days reduced to 6 days). Overall, the preoperative productivity costs were reduced after ESS ($9,190 vs. $3,373, respectively; P < .001). Daily productivity is negatively impacted by the presence of CRS. The outcomes from this study provide the first insights into the reduced productivity costs associated with receiving ESS for refractory CRS. Future studies with larger sample sizes will need to validate the results from this pilot study. 2c Laryngoscope, 126:570-574, 2016.


Functional foods and strategies contrasting bacterial adhesion.
Antibacterial strategies targeting bacterial adhesion to substrates are considered a valuable alternative to traditional antibiotic therapy, in view of the great advantage they bring in combating the infectious process at the very early stage without selecting for drug resistant cells. Amongst bioactive compounds with activity against bacterial adhesion, several are found in natural food and beverages, such as cranberry, tea, coffee, wine and milk. For the analysis of their anti-infective potential, successful experimental models can be conducted using different substrates from the oral cavity. Studies conducted so far in this field allowed the discovery of a variety of anti-adhesive fractions and compounds proven to be effective against bacterial traits involved in the development of oral pathologies such as caries and gingivitis/periodontitis. Discovering new anti-adhesive compounds from natural products, unravelling and testing their prophylactic and therapeutic values, and improving their use in the general population are promising new frontiers in the global fight against human infectious diseases.


"Medium-ring" strategy enables high-performance narrowband pure-blue multi-resonance emitters: boost provided by a unique perpendicular geometry.
The introduction of a heptagonal tribenzo[b,d,f]azepine (TBA) donor onto BCz-BN enabled the development of a pure-blue narrowband emitter, TBA-BCz-BN, and induced a significant blue shift of emission from 483 nm to 468 nm and a decrease in the singlet-triplet energy gap from 0.17 eV to 0.14 eV. The corresponding TBA-BCz-BN-based OLED exhibited a high external quantum efficiency of 30.8%.


Estimating the impact of newly arrived foreign-born persons on tuberculosis in the United States.
Among approximately 163.5 million foreign-born persons admitted to the United States annually, only 500,000 immigrants and refugees are required to undergo overseas tuberculosis (TB) screening. It is unclear what extent of the unscreened nonimmigrant visitors contributes to the burden of foreign-born TB in the United States. We defined foreign-born persons within 1 year after arrival in the United States as "newly arrived", and utilized data from U.S. Department of Homeland Security, U.S. Centers for Disease Control and Prevention, and World Health Organization to estimate the incidence of TB among newly arrived foreign-born persons in the United States. During 2001 through 2008, 11,500 TB incident cases, including 291 multidrug-resistant TB incident cases, were estimated to occur among 20,989,738 person-years for the 1,479,542,654 newly arrived foreign-born persons in the United States. Of the 11,500 estimated TB incident cases, 41.6% (4,783) occurred among immigrants and refugees, 36.6% (4,211) among students/exchange visitors and temporary workers, 13.8% (1,589) among tourists and business travelers, and 7.3% (834) among Canadian and Mexican nonimmigrant visitors without an I-94 form (e.g., arrival-departure record). The top 3 newly arrived foreign-born populations with the largest estimated TB incident cases per 100,000 admissions were immigrants and refugees from high-incidence countries (e.g., 2008 WHO-estimated TB incidence rate of ≥100 cases/100,000 population/year; 235.8 cases/100,000 admissions, 95% confidence interval [CI], 228.3 to 243.3), students/exchange visitors and temporary workers from high-incidence countries (60.9 cases/100,000 admissions, 95% CI, 58.5 to 63.3), and immigrants and refugees from medium-incidence countries (e.g., 2008 WHO-estimated TB incidence rate of 15-99 cases/100,000 population/year; 55.2 cases/100,000 admissions, 95% CI, 51.6 to 58.8). Newly arrived nonimmigrant visitors contribute substantially to the burden of foreign-born TB in the United States. To achieve the goals of TB elimination, direct investment in global TB control and strategies to target nonimmigrant visitors should be considered.


Hydrothermal treatment of bottom ash from the incineration of municipal solid waste: retention of Cs(I), Cd(II), Pb(II) and Cr(III).
The retention of Cs+, Cd2+, Pb2+ and Cr3+ by the compounds formed as a result of the hydrothermal treatment of the bottom ash from the fluidized-bed incineration of municipal solid wastes is examined in this work. The amount of Cs+ retained and the distribution coefficient, Kd, were considerably lower than those for Cd2+, Pb2+ and Cr3+, independently of the type of compounds formed by the different bottom ash treatments. The high percentage of Cs+ retained (31%), with a Kd of 222 ml/g, occurred after treatment of the bottom ash in NaOH at 200 degrees C, where zeolite-type A (Na6[AlSiO4]6.4H2O) was the major compound, together with aluminum tobermorite (Ca5Si5Al(OH)O17.5H2O). In the case of Cd2+, Pb2+ and Cr3+, the amount retained was approximately 99% under all of the conditions studied.


Reduced number, G protein coupling, and antinociceptive efficacy of spinal mu-opioid receptors in diabetic rats are reversed by nerve growth factor.
This study investigated putative mechanisms of impaired spinal opioid antinociception such as a downregulation of mu-opioid receptor (MOR) number, coupling, and efficacy in rats with advanced (12 weeks) streptozotocin (STZ)-induced diabetes. Intravenous injection of STZ (45 mg/kg) in Wistar rats led to selective degeneration of insulin-producing pancreatic ß-cells, elevated blood glucose, and mechanical hyperalgesia. In these animals, dose-dependent and naloxone-reversible intrathecal fentanyl antinociception was significantly impaired and associated with a loss in MOR immunoreactivity of calcitonin gene-related peptide-immunoreactive (CGRP-IR) sensory nerve terminals, membrane-bound MOR binding sites, and MOR-stimulated G protein coupling within the dorsal horn of the spinal cord. Intrathecal delivery of nerve growth factor (NGF) in diabetic animals normalized spinal MOR number and G protein coupling and rescued spinal fentanyl-induced antinociception. These findings identify for the first time a loss in functional MOR on central terminals of sensory neurons as a contributing factor for the impaired spinal opioid responsiveness during advanced STZ-induced diabetes that can be reversed by NGF. Moreover, they support growing evidence of a distinct regulation of opioid responsiveness during various painful states of disease (eg, arthritis, cancer, neuropathy) and may give novel therapeutic incentives. In diabetic neuropathy a loss in sensory neuron mu-opioid receptor number and coupling contributes to impaired spinal opioid antinociception that can be reversed by NGF. These findings support growing evidence of a distinct regulation of opioid responsiveness during various painful diseases and may give novel therapeutic incentives.


Tensor decomposition of TMS-induced EEG oscillations reveals data-driven profiles of antiepileptic drug effects.
Transcranial magnetic stimulation combined with electroencephalography is a powerful tool to probe human cortical excitability. The EEG response to TMS stimulation is altered by drugs active in the brain, with characteristic "fingerprints" obtained for drugs of known mechanisms of action. However, the extraction of specific features related to drug effects is not always straightforward as the complex TMS-EEG induced response profile is multi-dimensional. Analytical approaches can rely on a-priori assumptions within each dimension or on the implementation of cluster-based permutations which do not require preselection of specific limits but may be problematic when several experimental conditions are tested. We here propose an alternative data-driven approach based on PARAFAC tensor decomposition, which provides a parsimonious description of the main profiles underlying the multidimensional data. We validated reliability of PARAFAC on TMS-induced oscillations before extracting the features of two common anti-epileptic drugs (levetiracetam and lamotrigine) in an integrated manner. PARAFAC revealed an effect of both drugs, significantly suppressing oscillations in the alpha range in the occipital region. Further, this effect was stronger under the intake of levetiracetam. This study demonstrates, for the first time, that PARAFAC can easily disentangle the effects of subject, drug condition, frequency, time and space in TMS-induced oscillations.


Distribution of neuropeptide Y in the lower brainstem: an immunohistochemical analysis.
The distribution of neuropeptide Y (NPY)-like immunoreactive (NPYI) structures in the rat lower brainstem was examined by means of indirect immunofluorescence or peroxidase-antiperoxidase methods. In addition to the well known immunoreactive NPYI containing cell groups, the present study demonstrated a much wider distribution of immunoreactive NPYI cells in the lower brainstem, i.e. substantia nigra pars lateralis, interpeduncular nucleus, inferior colliculus, nucleus cuneiformis, dorsal tegmental nucleus of Gudden, nucleus laterodorsalis tegmenti, nucleus vestibularis medialis, nucleus vestibularis inferioris, in the fasciculus longitudinalis medialis and nucleus parvocellularis compacta. We also demonstrated an extensive network of NPYI fibers in various areas of the lower brainstem including the auditory system, viscerosensory system, visceromotor system, raphe nuclei, reticular formation, parabrachial area, locus coeruleus and interpeduncular nucleus, etc. The possible importance of NPY is briefly discussed.


ETA receptor blockade decreases vascular superoxide generation in DOCA-salt hypertension.
Development and progression of end-organ damage in hypertension have been associated with increased oxidative stress. Superoxide anion accumulation has been reported in deoxycorticosterone acetate (DOCA)-salt hypertension, in which endothelin-1 plays an important role in cardiovascular damage. We hypothesized that blockade of ETA receptors in DOCA-salt rats would decrease oxidative stress. Both systolic blood pressure (SBP, 210+/-9 mm Hg; P<0.05) and vascular superoxide generation in vivo were increased in DOCA-salt (44.9+/-10.3% of ethidium bromide-positive nuclei; P<0.05) versus control uninephrectomized (UniNx) rats (118+/-3 mm Hg; 18.5+/-3%, respectively). In DOCA-salt rats, the ETA antagonist BMS 182874 (40 mg/kg per day PO) lowered SBP (170+/-4 versus UniNx, 120+/-3 mm Hg) and normalized superoxide production (21.7+/-6 versus UniNx, 11.9+/-7%). Vitamin E (200 mg/kg per day PO) decreased superoxide formation in DOCA-salt rats (18.8+/-7%) but did not alter SBP. Oxidative stress in nonstimulated circulating polymorphonuclear cells (PMNs) or in PMNs treated with zymosan, an inducer of superoxide release, was similar in DOCA-salt and UniNx groups. Superoxide formation by PMNs was unaffected by treatment with BMS 182874. Western blot analysis showed increased nitrotyrosine-containing proteins in mesenteric vessels from DOCA-salt compared with UniNX. Treatment with either BMS 182874 or vitamin E abolished the differences in vascular nitrotyrosine-containing proteins between DOCA-salt and UniNX. Maximal relaxation to acetylcholine was decreased in DOCA-salt aortas (75.8+/-4.2% versus UniNx, 95.4+/-1.9%, P<0.05). BMS 182874 treatment increased acetylcholine-induced relaxation in DOCA-salt aortas to 93.5+/-4.5%. These in vivo findings indicate that increased vascular superoxide production is associated with activation of the endothelin system through ETA receptors in DOCA-salt hypertension, in apparently blood pressure-independent fashion.


Atypical metastasis of nasopharyngeal cancer: noncontiguous spread to the ipsilateral ear.
Nasopharyngeal carcinoma (NPC) is a rare form of squamous cell carcinoma. Primary NPC is generally treated with radiation and chemotherapy, though recurrence and distant metastases are common. Reports of noncontiguous metastasis to the middle ear and external ear canal (EAC) are rare. Case presentation of a female patient previously treated for NPC, who developed an EAC metastasis. A literature review of all reported cases of metastatic NPC in the middle ear and EAC is also included. A patient presenting with noncontiguous metastasis of NPC to the EAC was treated with surgical resection followed by chemotherapy and radiation. The patient successfully completed treatment and is currently alive but with suspected distant metastatic disease at 11 months following treatment. NPC metastasis to the EAC is extremely rare. Treatment options are varied, and prognosis is generally poor. The case presented here shows better outcomes than many previous reports.


Aminoglycoside ototoxicity in the chick (Gallus domesticus) inner ear: I. The effects of kanamycin and netilmicin on the basilar papilla.
A single dose (100 mg/kg of egg weight) of kanamycin or netilmicin was injected into the yolk sacs of 7-day-old chick (Gallus domesticus) embryos. Embryos were collected every 24 hours and processed for light and transmission electron microscopy. Morphologic study of the medial basilar papilla disclosed that both kanamycin and netilmicin are toxic to the hair cells in this region. Intoxication was manifested by an increased number of dense osmiophilic bodies, swollen mitochondria, agglomerated chromatin, and occasional disorganization of the kinocilium basal bodies. The cytologic changes observed in the hair cells of embryos injected with netilmicin and kanamycin were similar. However, mitochondrial damage was more severe in the chicks after kanamycin than after netilmicin injection. Some of the cytologic alterations described here are comparable to those already reported for aminoglycoside-intoxicated hair cells in several mammalian species. This study and previous work indicate that the chick embryo provides a satisfactory developmental model for testing ototoxicity of drugs in vivo.


The central administration of vitisin a, extracted from Vitis vinifera, improves cognitive function and related signaling pathways in a scopolamine-induced dementia model.
Neurodegenerative disorders, such as Alzheimer's disease (AD), are characterized by cognitive function loss and progressive memory impairment. Vitis vinifera, which is consumed in the form of fruits and wines in various countries, contains several dietary stilbenoids that have beneficial effects on neuronal disorders related to cognitive impairment. However, few studies have investigated the hypothalamic effects of vitisin A, a resveratrol tetramer derived from V. vinifera stembark, on cognitive functions and related signaling pathways. In this study, we conducted in vitro, ex vivo, and in vivo experiments with multiple biochemical and molecular analyses to investigate its pharmaceutical effects on cognitive functions. Treatment with vitisin A increased cell viability and cell survival under H2O2-exposed conditions in a neuronal SH-SY5 cell line. Ex vivo experiments showed that vitisin A treatment restored the scopolamine-induced disruption of long-term potentiation (LTP) in the hippocampal CA3-CA1 synapse, indicating the restoration of synaptic mechanisms of learning and memory. Consistently, central administration of vitisin A ameliorated scopolamine-induced disruptions of cognitive and memory functions in C57BL/6 mice, as evidenced by Y-maze and passive avoidance tests. Further studies showed that vitisin A upregulates BDNF-CREB signaling in the hippocampus. Together, our findings suggest that vitisin A exhibits neuroprotective effects, at least partially, by upregulating BDNF-CREB signaling and LTP.


Longitudinal mortality of preserved ratio impaired spirometry in a middle-aged Asian cohort.
Although preserved ratio impaired spirometry (PRISm) has been determined to have poor prognosis, it is a heterogeneous state, and studies regarding its prognosis in Asians are limited. This study investigated the long-term all-cause and cardiovascular mortality of patients with PRISm compared with those of patients with chronic obstructive pulmonary disease (COPD) and normal individuals in the Korean middle-aged general population. Participants were recruited between 2001 and 2002 from a community-based prospective cohort in South Korea. Mortality data were collected over a 16.5-year mean follow-up period. The all-cause and cardiovascular mortality risks of PRISm were compared between patients with COPD and healthy controls. The PRISm group had a mean age of 53.4 years and mean body mass index of 24.9 kg/m2; furthermore, 55.2% of the PRISm patients had never smoked, and the prevalence of comorbidities was not higher than that in the other groups. Compared with normal individuals, PRISm patients did not show increased all-cause mortality, whereas COPD patients showed increased all-cause mortality (PRISm: adjusted hazard ratio [aHR], 1.19; 95% confidence interval [CI], 0.85-1.65; COPD: aHR, 1.34, 95% CI, 1.07-1.69). Furthermore, the PRISm patients did not show increased cardiovascular mortality compared with normal individuals (PRISm: aHR, 1.65; 95% CI, 0.92-2.95; COPD: aHR, 1.83; 95% CI, 1.09-3.07). In our population-based cohort, all-cause and cardiovascular mortality risk did not increase in individuals with PRISm compared with normal individuals. Further studies are needed to distinguish a lower-risk subgroup of PRISm with certain characteristics, such as middle-aged, light-smoking Asians without additional cardiovascular risk.


Home visitation programs for at-risk young families. A systematic literature review.
This systematic literature review is stimulated by the perceived need of investigator, practice and policy stakeholders for a complete but parsimonious summary of key elements of programs that use home visitation for at-risk young families as the major delivery method. To describe the program components, practices, outcomes, and reliability of the evaluation approaches. Computer and hand searches of literature were carried out. Reports of established programs, from the last five years, that describe home visitation services to at-risk families were included. A comprehensive data collection tool was used in the analysis of the findings. Improvements over the previous five years were seen in the following areas: use of early intervention model, inclusion of comparison groups and adequate sampling. Challenges remain in development, targeting and reporting of home visitation practice, overall lack of impact, differential effects by program site, retention of participants and appropriate measurement.


The acid-base and biochemical characteristics of intrapartum fetal asphyxia.
The maternal and fetal acid-base, lactate, and pyruvate characteristics during the course of labor and at delivery were studied in 124 patients delivered of an infant with evidence of metabolic acidosis at delivery. This metabolic acidosis is principally caused by hyperlactatemia resulting from the tissue oxygen debt accompanying fetal asphyxia. Hypoxemia was one mechanism contributing to this fetal asphyxia and tissue oxygen debt. This evidence of fetal asphyxia developed during the last half and principally during the last two hours of the intrapartum period. Acid-base assessment of fetal blood with identification of a metabolic acidosis will provide an accurate objective diagnosis of intrapartum fetal asphyxia.