Factors contributing to poor COVID-19 outcomes in diabetic patients: Findings from a single-center cohort study.
Diabetes Mellitus (DM) is a frequent comorbidity in patients infected with the SARS-CoV-2 virus. The risk of developing severe or critical COVID-19 and higher mortality was observed to be increased in diabetic patients hospitalized due to COVID-19. In this study we aimed to find out the impact of clinical characteristics, comorbidities, laboratory results, and complications on the outcomes of diabetic patients hospitalized due to COVID-19. This article is a retrospective cohort study that include diabetic patients hospitalized with COVID-19 infection. A definition of diabetes was based on the past history of diabetes or if the HbA1c was 6.5% or higher. Demographics, clinical characteristics, comorbidities, laboratory results, and complications were extracted from the electronic medical records. The mortality rate increased with increasing age (from 5.56% in younger patients to 46% in the elderly) and with severity (from 25.71% in moderate cases to 43.77% in critical cases). We found that a critical severity on admission (OR: 5.26, 95% CI: 1.28-21.66, p = 0.0214), a history of stroke (OR: 8.37, 95% CI: 2.2-31.88, p = 0.0018), and low calcium levels on admission (OR: 2.23, 95% CI: 1.01-4.91, p = 0.0475) were significant risk factors predicting higher COVID-19 mortality in diabetic patients. The findings of this study suggest that reduced calcium levels could potentially indicate higher mortality due to COVID-19 in patients with DM. Furthermore, careful monitoring of diabetic patients hospitalized due to COVID-19 infection, especially those with critical disease severity or those with a history of stroke, may improve their outcome and lessen mortality.


Getting to the heart of hypopituitarism.
A 53-year-old woman was diagnosed with hypopituitarism following an acute presentation with cardiac tamponade and hyponatraemia, having recently been investigated for a pericardial effusion. Secondary hypothyroidism is a rare cause of pericardial effusion and tamponade, but an important differential to consider. Management requires appropriate hormone replacement and, critically, a low threshold for commencing stress dose steroids. Clinical signs classically associated with cardiac tamponade are frequently absent in cases of tamponade due to primary and secondary hypothyroidism, and the relatively volume deplete state of secondary hypoadrenalism in hypopituitarism may further mask an evolving tamponade, as the rise in right atrial pressure is less marked even in the presence of large effusion. Our case demonstrates the importance of a high index of suspicion for cardiac tamponade in this patient cohort, even in the absence of clinical signs, and for measuring both thyroid-stimulating hormone and thyroxine levels when evaluating a pericardial effusion.


[Calcium distribution in the central cell of lettuce (Lactuca sativa L.) before and after pollination].
Potassium antimonite precipitation was used to locate calcium in the central cell of lettuce (Lactuca sativa L.) before and after pollination. At 3d before anthesis, two polar nuclei of central cell separately located at two polarity of the cell, and few calcium precipitates (ppts) appeared in the polar nuclei and cytoplasm, but some ppts in its small vacuoles. At 2d before anthesis, two polar nuclei moved toward the middle of the cell and fused to form a secondary nucleus, and the ppts evidently increased in the nucleus and cytoplasm. At 1d before anthesis, secondary nucleus again moved toward micropylar end and located near the egg to prepare for fertilization. Calcium precipitates were mainly accumulated in the secondary nucleus. After pollination and before fertilization, the distribution of calcium ppts was similar to that before pollination. At 4h after pollination, the central cell was fertilized, and calcium ppts evidently increased in the cell and numerous were accumulated in its nucleus and cytoplasm. At 6h after pollination, the primary endosperm nucleus completed its first division and formed two dissociate endosperm nuclei, and still many calcium precipitates appeared in the nucleus and cytoplasm. With endosperm development, calcium ppts decreased in the endosperm cell. At 1d after emasculated and without pollination, the secondary nucleus of the cell still bordered on the egg and some calcium ppts appeared in the secondary nucleus. The results indicated that the temporal and spatial changes of calcium in the central cell may play an important physiological role during the development of the central cell and endosperm.


Bacteria mature preproinsulin to proinsulin.
By inserting the rat preproinsulin gene into the bacterial prepenicillinase gene, we formed a variety of hybrid bacterial-eukaryotic signal sequences attached to proinsulin. Among these were the four following constructions: rat proinsulin attached to the entire penicillinase signal sequence and rat preproinsulin fused to all of, to half of, or only to the first four amino acids of the bacterial signal sequence. In all four cases, more than 90% of the rat insulin antigen appeared in the periplasmic space. By immunoprecipitation and determination of the amino acid sequences of the radiolabeled products, we show that the bacteria correctly process both the bacterial and the eukaryotic signal sequences of these hybrid proteins. The cleavage of the eukaryotic signal by bacterial peptidase, in this case, generates proinsulin.


Treprostinil, a prostacyclin analogue, in pulmonary arterial hypertension associated with connective tissue disease.
To assess the efficacy and safety of continuous subcutaneous infusion of treprostinil, a stable prostacyclin analogue, for treating pulmonary arterial hypertension (PAH) in patients with connective tissue disease (CTD). Two multicenter, randomized, double-blind, placebo-controlled, prospective trials of treprostinil vs placebo in 470 patients with PAH. A subset of 90 patients with PAH and CTD, including systemic lupus erythematosus, diffuse scleroderma, limited scleroderma, and mixed CTD/overlap syndrome. Patients received either treprostinil (initiated at 1.25 ng/kg/min, and titrated upward) or placebo via continuous subcutaneous infusion. The maximum dose of treprostinil allowed was 22.5 ng/kg/min. Six-minute walk (6MW) distance and dyspnea-fatigue scores were determined at baseline, and at 6 weeks and 12 weeks. Hemodynamic measures were obtained at baseline and at 12 weeks. At baseline, most patients had New York Heart Association class III symptoms. The mean baseline 6MW distance was 289 m (range, 60 to 448 m). The mean dose of treprostinil at week 12 was 8.4 ng/kg/min (range, 1.25 to 17.5 ng/kg/min). After 12 weeks, the change in cardiac index from baseline was + 0.2 +/- 0.08 L/min/m(2) in the treprostinil group and - 0.07 +/- 0.07 L/min/m(2) in the placebo group (p = 0.007). The pulmonary vascular resistance index decreased by 4 +/- 2 U x m(2) in the treprostinil group and increased by 1 +/- 1 U x m(2) in the placebo group (p = 0.006). The placebo-corrected median improvement from baseline in 6MW distance was 25 m in treprostinil-treated patients (p = 0.055); this improvement appeared to be dose related. Dyspnea fatigue scores also improved in the treprostinil group compared with the placebo group (p = 0.014). Adverse events included infusion site pain and typical side effects related to prostaglandins, and were tolerated by most patients. Continuous subcutaneous infusion of treprostinil in patients with PAH associated with CTD improved exercise capacity, symptoms of PAH, and hemodynamics.


Barrett's oesophagus--radiological features in 100 cases.
The columnar-lined or Barrett's oesophagus is an acquired condition resulting from long-continued gastro-oesophageal reflux. In the last 20 years 149 patients with Barrett's oesophagus have been studied in the clinics of the Johannesburg Teaching Hospitals. Important radiological predictors of Barrett's oesophagus, as defined from a series of 100 cases, are the presence of a stricture well above the gastro-oesophageal junction (41 cases), a long stricture (13 cases) and ulceration in the body of the oesophagus (16 cases). An early stricture may be so subtle that it is missed or disregarded, and is the usual site of the squamocolumnar junction. Significant strictures may be seen even in the absence of a hiatus hernia. When associated with a hiatus hernia the strictures are usually concentric and are longer than the usual reflux strictures. The varying length of these strictures suggests an upward progression of the disease process, which begins at the gastro-oesophageal junction. This feature, seen in 6 of our patients, has not previously been stressed as a predictor for Barrett's oesophagus. Radiological reflux, although in itself a poor predictor, lends support to the diagnosis of Barrett's oesophagus if one or more of the other predictors is present. A less important predictor is a reticular mucosal pattern seen on double-contrast radiography.


[Dalbavancin: pharmacokinetic and pharmacodynamic parameters].
Dalbavancin is a new lipoglycopeptide antibiotic whose structure influences its pharmacokinetic profile. It is not absorbed after oral administration and is therefore administered intravenously. It is distributed through intracellular fluid, reaching adequate concentrations in the skin, bone, blister fluid and synovial fluid. Plasma protein binding is very high. Concentrations in brain tissue and cerebrospinal fluid (CSF) are inadequate. Excretion is through non-microsomal metabolism with inactive metabolites and through the kidneys by glomerular filtration. Dalbavancin is eliminated slowly, as shown by its clearance value and its terminal elimination half-life, which exceeds 300 hours. This means that adequate concentrations of the drug remain in plasma and tissues for a prolonged period and explains the dosing regimen: a first dose of 1g followed 7 days later by a 500mg dose. The pharmacokinetics are linear and show little intra- and interindividual variability. There are no pharmacokinetic interactions. Dose adjustment is not required for patients with mild or moderate renal insufficiency (creatinine clearance ≥ 30 to 79ml/min). Dosage adjustment is not required in patients regularly receiving elective haemodialysis (3 times/week) and the drug can be administered without consideration of haemodialysis times. In patients with chronic renal insufficiency, whose creatinine clearance is < 30ml/min and who are not regularly receiving elective haemodialysis, the recommended dose should be reduced to 750mg per week, followed 1 week later by 375mg. Dosage adjustment does not seem necessary in patients with liver failure or in older patients. There is no information on the most appropriate dosage in children. The pharmacokinetic/pharmacodynamics parameter that best describes the effectiveness of dalbavancin is the ratio between the area under the curve and the minimum inhibitory concentration.


The Companion Dog as a Model for the Longevity Dividend.
The companion dog is the most phenotypically diverse species on the planet. This enormous variability between breeds extends not only to morphology and behavior but also to longevity and the disorders that affect dogs. There are remarkable overlaps and similarities between the human and canine species. Dogs closely share our human environment, including its many risk factors, and the veterinary infrastructure to manage health in dogs is second only to the medical infrastructure for humans. Distinct breed-based health profiles, along with their well-developed health record system and high overlap with the human environment, make the companion dog an exceptional model to improve understanding of the physiological, social, and economic impacts of the longevity dividend (LD). In this review, we describe what is already known about age-specific patterns of morbidity and mortality in companion dogs, and then explore whether this existing evidence supports the LD. We also discuss some potential limitations to using dogs as models of aging, including the fact that many dogs are euthanized before they have lived out their natural life span. Overall, we conclude that the companion dog offers high potential as a model system that will enable deeper research into the LD than is otherwise possible.


Work-related stress and cortisol levels: is there an association? Results of an observational study.
Chronic exposure to work-related stress (WRS) stimulates the hypothalamic-pituitary-adrenal (HPA) axis to increase glucocorticoid secretion, including cortisol, and these hormones can be measured both in serum and urine. The Health Safety Executive Toolkit (HSE) questionnaire is used to assess WRS risk objectively. The scope of our study is to investigate whether serum or urinary cortisol levels could be used as alternative objective indicators of WRS, specifically in those subjects who are chronically exposed to it. 130 patients (75 males and 55 females, mean age 47.7 ± 11.3 years) were evaluated at a specialized Centre for Secondary Hypertension, where both their serum (8 AM) and 24-hours urinary cortisol were measured and they were asked to complete two questionnaires: one questionnaire to collect data about their socio-demographic and job characteristics, and the HSE questionnaire to evaluate WRS. Multiple linear regression analysis showed an association of urinary cortisol with several variables: tobacco smoke (β = 69.6; p = 0.003); female gender (β = -37.3; p = 0.041); exposure to physical risks (β = 51.8; p = 0.032); control score (β = -22.7; p = 0.039); role score (β= 39.3; p = 0.020). Age was the only variable associated with serum cortisol levels (β = -3.6; p = 0.042). Urinary cortisol levels, but not serum levels, are associated with variables linked to WRS (score control and role) and to socio-demographic variables, namely gender and tobacco smoke. Thus, urinary cortisol can be considered a useful and non-invasive biological indicator to quantify WRS.


[Phenomenon of asynchrony of induced mediator release at the neuromuscular junction of the frog].
"Hump-like" distortions of evoked end-plate currents were observed with the help of extracellular focal recordings in sartorius and cutaneous frog muscle preparations at 20 degrees C. These distortions resembled spontaneous or unitary evoked responses by their amplitude and time course. Statistical analysis allowed rejecting the simplified assumption that these "humps" were the result of spontaneous nervous signals superimposed on the evoked ones. The asynchronous release of single quanta forming the multiquantal response seemed to be a more plausible explanation. A distinct correlation between the distribution of synaptic delay values of unitary responses (at low quantal content) and observed asynchronous responses (at high quantal content) was found. A polymodal pattern of distribution of synaptic delays was shown in both cases. It is concluded that the presence of asynchronous responses and discrete character of variations in synaptic delays are an intrinsic property of the transmitter release mechanism.


N2E: Envisioning a process to support transition from nurse to educator.
Abstract Rising health inequities, continuing nursing shortages, and overlooked professional development needs of nurse educators are three important issues facing nursing in Australia. This paper argues for an innovative and proactive strategy that could transform the nurse education workforce into one that is repopulated, reinvigorated and refocused. The problem facing nurse educators, and subsequently affecting nurses' preparation for practice and longevity in the profession, was identified by drawing on findings from the literature, extensive educational experience, and an exploratory study of nurse educators working in universities, colleges and health services. A solution has been devised by drawing together the tenets of critical social theory, transformative learning, communities of practice and social media. Nursing educators, refocused around a social justice agenda, may be the remedy that the Australian Health Care System requires to embark on effective action that can benefit everyone, from the health service staff to our most vulnerable groups in society. This refocusing can be achieved in a structured and strategic process that builds confidence and professional capabilities.


Observational Study of Chlorpromazine in Hospitalized Patients with COVID-19.
Chlorpromazine has been suggested as being potentially useful in patients with coronavirus disease 2019 (COVID-19) on the grounds of its potential antiviral and anti-inflammatory effects. The aim of this study was to examine the association between chlorpromazine use and mortality among adult patients hospitalized for COVID-19. We conducted an observational, multicenter, retrospective study at Assistance Publique-Hôpitaux de Paris (AP-HP) Greater Paris University hospitals. Study baseline was defined as the date of first prescription of chlorpromazine during hospitalization for COVID-19. The primary endpoint was death. Among patients who had not been hospitalized in intensive care units (ICUs), we compared this endpoint between those who received chlorpromazine and those who did not, in time-to-event analyses adjusted for patient characteristics, clinical markers of disease severity, and other psychotropic medications. The primary analysis used a Cox regression model with inverse probability weighting. Multiple sensitivity analyses were performed. Of the 14,340 adult inpatients hospitalized outside ICUs for COVID-19, 55 patients (0.4%) received chlorpromazine. Over a mean follow-up of 14.3 days (standard deviation [SD] 18.2), death occurred in 13 patients (23.6%) who received chlorpromazine and 1289 patients (9.0%) who did not. In the primary analysis, there was no significant association between chlorpromazine use and mortality (hazard ratio [HR] 2.01, 95% confidence interval [CI] 0.75-5.40; p = 0.163). Sensitivity analyses included a Cox regression in a 1:5 ratio matched analytic sample that showed a similar result (HR 1.67, 95% CI 0.91-3.06; p = 0.100) and a multivariable Cox regression that indicated a significant positive association (HR 3.10, 95% CI 1.31-7.34; p = 0.010). Our results suggest that chlorpromazine prescribed at a mean daily dose of 70.8 mg (SD 65.3) was not associated with reduced mortality.


Seasonal hair follicle cycle of Camelus dromedarius.
This experiment was conducted to identify the annual changes in hair follicle activity, changes at the follicular level and to characterize some of the fibre-follicle characteristics of camels at different ages. A total of 28 camels were allocated at random on the basis of age to one of four groups (2, 4, 6 and older than 8 years). All groups of camels were fed a maintenance level of ration throughout the experiment. To determine hair follicle cycle and other follicle characteristics samples of skin were taken using a trephine from the right midside of animals at approximately 28 day intervals for a period of 12 months. Using a small hand clipper, 15 g of fibre sample was taken from the left midside region to determine fibre characteristics. Analysis of variance was performed using a one-way SAS package and the means and the standard deviations of means were generated with this program. Mean S/P ratio, primary and secondary and total follicle densities of all groups of camels were 6.85 +/- 0.75, 3.76 +/- 0.63, 22.29 +/- 3.57 and 25.33 +/- 3.85, respectively. Mean fibre diameter, percentage of medullated and non-medullated fibre and clean wool percentage of all groups were 18.98 +/- 1.64, 18.10 +/- 1.65, 81.89 +/- 6.98 and 77.58 +/- 4.58, respectively. Mean percentage of active primary follicles significantly (p < 0.05) decreased to lowest in February to a minimum of 83.1%, then significantly (p < 0.05) increased over spring. Secondary follicle activity decreased over winter and spring to a minimum of 60% in February.


Suspected acorn toxicity in nine horses.
Acorn toxicity has been anecdotally reported to cause fatal colitis and colic in horses but reports in the scientific literature are sparse. This study reports the diagnosis, treatment, prognosis and outcome of 9 cases with suspected acorn toxicity admitted to 2 referral hospitals. Retrospective case series. Case records from 2004 to 2013 were reviewed. Horses were included in the study if they met 3 of 4 criteria: exposure to acorns; clinical and laboratory data suggesting alimentary or renal dysfunction; acorn husks in the faeces or gastrointestinal tract; and necropsy and histopathological findings consistent with acorn toxicity. Data collected included case history, clinical presentation, clinicopathological data, ultrasonographic findings, case progression, and necropsy and histopathological findings. Nine horses met the inclusion criteria. Five cases presenting with haemorrhagic diarrhoea deteriorated rapidly and were subjected to euthanasia or died. Four cases showed signs of colic with gas distension, displacement of the large colon and diarrhoea. Three of these (33%) survived with medical management, the fourth was subjected to euthanasia. Post mortem examination of 6 cases demonstrated submucosal oedema of the large intestine and caecum (n = 6), acute tubular nephrosis (n = 6), diffuse necrohaemorrhagic and ulcerative typhlocolitis and enteritis (n = 4), and small intestinal oedema (n = 3). Acorn ingestion may be associated with typhylocolitis leading to diarrhoea, colic and acute renal tubular nephrosis. Recovery is possible in mildly affected cases; more severe cases show hypovolaemia, intractable pain, renal dysfunction and cardiovascular failure, and often succumb to the disease process. Disease is only seen in a small proportion of the population exposed to acorns and there seems to be an increased occurrence in certain years. Further investigation into factors predisposing to disease is required, but limiting exposure to acorns in the autumn seems prudent.


Liver accumulation of Plasmodium chabaudi-infected red blood cells and modulation of regulatory T cell and dendritic cell responses.
It is postulated that accumulation of malaria-infected Red Blood Cells (iRBCs) in the liver could be a parasitic escape mechanism against full destruction by the host immune system. Therefore, we evaluated the in vivo mechanism of this accumulation and its potential immunological consequences. A massive liver accumulation of P. c. chabaudi AS-iRBCs (Pc-iRBCs) was observed by intravital microscopy along with an over expression of ICAM-1 on day 7 of the infection, as measured by qRT-PCR. Phenotypic changes were also observed in regulatory T cells (Tregs) and dendritic cells (DCs) that were isolated from infected livers, which indicate a functional role for Tregs in the regulation of the liver inflammatory immune response. In fact, the suppressive function of liver-Tregs was in vitro tested, which demonstrated the capacity of these cells to suppress naive T cell activation to the same extent as that observed for spleen-Tregs. On the other hand, it is already known that CD4+ T cells isolated from spleens of protozoan parasite-infected mice are refractory to proliferate in vivo. In our experiments, we observed a similar lack of in vitro proliferative capacity in liver CD4+ T cells that were isolated on day 7 of infection. It is also known that nitric oxide and IL-10 are partially involved in acute phase immunosuppression; we found high expression levels of IL-10 and iNOS mRNA in day 7-infected livers, which indicates a possible role for these molecules in the observed immune suppression. Taken together, these results indicate that malaria parasite accumulation within the liver could be an escape mechanism to avoid sterile immunity sponsored by a tolerogenic environment.


Biological control of ticks.
Ticks have numerous natural enemies, but only a few species have been evaluated as tick biocontrol agents (BCAs). Some laboratory results suggest that several bacteria are pathogenic to ticks, but their mode of action and their potential value as biocontrol agents remain to be determined. The most promising entomopathogenic fungi appear to be Metarhizium anisopliae and Beauveria bassiana, strains of which are already commercially available for the control of some pests. Development of effective formulations is critical for tick management. Entomopathogenic nematodes that are pathogenic to ticks can potentially control ticks, but improved formulations and selection of novel nematode strains are needed. Parasitoid wasps of the genus Ixodiphagus do not typically control ticks under natural conditions, but inundative releases show potential value. Most predators of ticks are generalists, with a limited potential for tick management (one possible exception is oxpeckers in Africa). Biological control is likely to play a substantial role in future IPM programmes for ticks because of the diversity of taxa that show high potential as tick BCAs. Considerable research is required to select appropriate strains, develop them as BCAs, establish their effectiveness, and devise production strategies to bring them to practical use.


Effect of antibacterial agents on the surface hardness of a conventional glass-ionomer cement.
In atraumatic restorative treatment (ART), caries removal with hand excavation instruments is not as efficient as that with rotary burs in eliminating bacteria under the glass ionomer cements (GICs). Thus, different antibacterial agents have been used in recent studies to enhance the antibacterial properties of the GICs, without jeopardizing their basic physical properties. The objective of this study was to evaluate the effect of antibacterial agents on the surface hardness of a conventional GIC (Fuji IX) using Vickers microhardness [Vickers hardness number (VHN)] test. Cetrimide (CT), cetylpyridinium chloride (CPC) and chlorhexidine (CHX) were added to the powder and benzalkonium chloride (BC) was added to the liquid of Fuji IX in concentrations of 1% and 2%, and served as the experimental groups. A control group containing no additive was also prepared. After the completion of setting reaction, VHN measurements were recorded at 1, 7, 15, 30, 60, and 90 days after storage in 37°C distilled water. A one-way ANOVA was performed followed by a Dunnett t test and Tamhane T2 tests and also repeated measurements ANOVA was used for multiple comparisons in 95% confidence interval. VHN results showed significant differences between the control and the experimental groups at all time periods (p<0.05 for all). Significant differences were observed between all study periods for individual groups (p<0.05). After 7 days, VHNs were decreased in all experimental groups while they continued to increase in the control group. BC and CHX groups demonstrated the least whereas CT and CPC groups exhibited most adverse effect on the hardness of set cements. Despite the decreased microhardness values in all experimental groups compared to the controls after 7 up to 90 days, incorporating certain antibacterial agents into Fuji IX GIC showed tolerable microhardness alterations within the limitations of this in vitro study.


Air pollution and climate-forcing impacts of a global hydrogen economy.
If today's surface traffic fleet were powered entirely by hydrogen fuel cell technology, anthropogenic emissions of the ozone precursors nitrogen oxide (NOx) and carbon monoxide could be reduced by up to 50%, leading to significant improvements in air quality throughout the Northern Hemisphere. Model simulations of such a scenario predict a decrease in global OH and an increased lifetime of methane, caused primarily by the reduction of the NOx emissions. The sign of the change in climate forcing caused by carbon dioxide and methane depends on the technology used to generate the molecular hydrogen. A possible rise in atmospheric hydrogen concentrations is unlikely to cause significant perturbations of the climate system.


New Antibiotics for Hospital-Acquired Pneumonia and Ventilator-Associated Pneumonia.
Hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) represent one of the most common hospital-acquired infections, carrying a significant morbidity and risk of mortality. Increasing antibiotic resistance among the common bacterial pathogens associated with HAP and VAP, especially Enterobacterales and nonfermenting gram-negative bacteria, has made the choice of empiric treatment of these infections increasingly challenging. Moreover, failure of initial empiric therapy to cover the causative agents associated with HAP and VAP has been associated with worse clinical outcomes. This review provides an overview of antibiotics newly approved or in development for the treatment of HAP and VAP. The approved antibiotics include ceftobiprole, ceftolozane-tazobactam, ceftazidime-avibactam, meropenem-vaborbactam, imipenem-relebactam, and cefiderocol. Their major advantages include their high activity against multidrug-resistant gram-negative pathogens.


Hatchery Vaccination Against Poultry Viral Diseases: Potential Mechanisms and Limitations.
Commercial broiler and layer chickens are heavily vaccinated against economically important viral diseases with a view of preventing morbidity, mortality, and production impacts encountered during short production cycles. Hatchery vaccination is performed through in ovo embryo vaccination prehatch or spray and subcutaneous vaccinations performed at the day of hatch before the day-old chickens are being placed in barns with potentially contaminated environments. Commercially, multiple vaccines (e.g., live, live attenuated, and viral vectored vaccines) are available to administer through these routes within a short period (embryo day 18 prehatch to day 1 posthatch). Although the ability to mount immune response, especially the adaptive immune response, is not optimal around the hatch, it is possible that the efficacy of these vaccines depends partly on innate host responses elicited in response to replicating vaccine viruses. This review focuses on the current knowledge of hatchery vaccination in poultry and potential mechanisms of hatchery vaccine-mediated protective responses and limitations.


Functional characterization of hypothalamic hyperprolactinemia.
PRL secretory dynamics were evaluated by several stimulation and suppression tests in nine patients with hyperprolactinemia due to organic hypothalamic disease. Basal PRL levels ranged between 20-63 ng/ml. There was a normal PRL response to TRH in eight cases (i.e. doubling of basal levels), whereas none of the seven tested subjects responded to sulpiride. The same dissociation of responses was not observed in any of the patients who were still hyperprolactinemic after surgery. Concomitant dopamine infusion resulted in sulpiride-induced PRL release in the four subjects so studied. None of 50 other hyperprolactinemic patients (11 with macroprolactinoma, 18 with microprolactinoma, and 21 with idiopathic hyperprolactinemia) showed PRL response to TRH but not to sulpiride. The TRH-induced PRL increase was significantly higher than that induced by sulpiride in hypothalamic hyperprolactinemia and significantly lower in idiopathic disease as well as in healthy controls; no differences were found in prolactinoma patients. The administration of substances resulting in stimulation of pituitary dopamine receptors, such as dopamine and L-dopa, induced a normal PRL suppression in 7 patients with hypothalamic disease so tested, whereas central nervous system-acting dopaminergic drugs, such as carbidopa plus L-dopa and nomifensine, failed to lower PRL levels in most cases (even when normoprolactinemic after surgery). These data suggest that the mild to moderate hyperprolactinemia found in many patients with hypothalamic lesions is due to dopamine deficiency at the pituitary level, that TRH and dopamine receptors at the lactotropes are intact in this condition, and that paired TRH and sulpiride tests may be of some diagnostic utility in hyperprolactinemic patients. They further suggest that subjects with so-called idiopathic hyperprolactinemia do not suffer from the type of hypothalamic derangement exhibited by patients with organic lesions of the hypothalamus.


Modified head shake computerized dynamic posturography.
Recent research on head shake posturography has demonstrated a modest increase in sensitivity to identifying peripheral vestibular system asymmetry when horizontal head movements were added to portions of the standard Sensory Organization Test (SOT) battery. However, limitations with respect to the head shake protocol were outlined, and usable data for assessing performance could not be established. The purpose of this study was to test a change in protocol for use of head shake SOT to address the noted limitations. Forty participants ranging in age from 20 to 79 years with no history of dizziness completed Conditions 2 and 5 of the SOT portion of computerized dynamic posturography on EquiTest equipment, while maintaining head still as well as 4 horizontal head movement velocity tasks. Slope of a linear regression fit to 6 performance points was used to characterize each participant. Spearman's ranked correlation (r) indicated a significant relationship between the slope of the line representing a decline in performance with age (r = -.52, p = .0006). The head shake modification showed a trend in increasing the separation of normal individuals across age and eliminated the limitations addressed in earlier research. Future research will investigate the head shake modification for identifying vestibular peripheral system asymmetries.


Addition of anti-leukotriene agents to inhaled corticosteroids in children with persistent asthma.
In the treatment of children with mild persistent asthma, low-dose inhaled corticosteroids (ICS) are recommended as the preferred monotherapy (referred to as step 2 of therapy). In children with inadequate asthma control on low doses of ICS (step 2), asthma management guidelines recommend adding an anti-leukotriene agent to existing ICS as one of three therapeutic options to intensify therapy (step 3). To compare the efficacy and safety of the combination of anti-leukotriene agents and ICS to the use of the same, an increased, or a tapering dose of ICS in children and adolescents with persistent asthma who remain symptomatic despite the use of maintenance ICS. In addition, we wished to determine the characteristics of people or treatments, if any, that influenced the magnitude of response attributable to the addition of anti-leukotrienes. We identified trials from the Cochrane Airways Group Specialised Register of Trials (CAGR), which were derived from systematic searches of bibliographic databases including the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, PsycINFO, AMED, and CINAHL; and the handsearching of respiratory journals and meeting abstracts, as well as the www.clinicaltrials.gov website. The search was conducted until January 2013. We considered for inclusion randomised controlled trials (RCTs) conducted in children and adolescents, aged one to 18 years, with asthma, who remained symptomatic despite the use of a stable maintenance dose of ICS and in whom anti-leukotrienes were added to the ICS if they were compared to the same, an increased, or a tapering dose of ICS for at least four weeks. We used standard methods expected by The Cochrane Collaboration. Five paediatric (parallel group or cross-over) trials met the inclusion criteria. We considered two (40%) trials to be at a low risk of bias. Four published trials, representing 559 children (aged ≥ six years) and adolescents with mild to moderate asthma, contributed data to the review. No trial enrolled preschoolers. All trials used montelukast as the anti-leukotriene agent administered for between four and 16 weeks. Three trials evaluated the combination of anti-leukotrienes and ICS compared to the same dose of ICS alone (step 3 versus step 2). No statistically significant group difference was observed in the only trial reporting participants with exacerbations requiring oral corticosteroids over four weeks (N = 268 participants; risk ratio (RR) 0.80, 95% confidence interval (CI) 0.34 to 1.91). There was also no statistically significant difference in percentage change in FEV₁ (forced expiratory volume in 1 second) with mean difference (MD) 1.3 (95% CI -0.09 to 2.69) in this trial, but a significant group difference was observed in the morning (AM) and evening (PM) peak expiratory flow rates (PEFR): N = 218 participants; MD 9.70 L/min (95% CI 1.27 to 18.13) and MD 10.70 (95% CI 2.41 to 18.99), respectively. One trial compared the combination of anti-leukotrienes and ICS to a higher-dose of ICS (step 3 versus step 3). No significant group difference was observed in this trial for participants with exacerbations requiring rescue oral corticosteroids over 16 weeks (N = 182 participants; RR 0.82, 95% CI 0.54 to 1.25), nor was there any significant difference in exacerbations requiring hospitalisation. There was no statistically significant group difference in withdrawals overall or because of any cause with either protocol. No trial explored the impact of adding anti-leukotrienes as a means to taper the dose of ICS. The addition of anti-leukotrienes to ICS is not associated with a statistically significant reduction in the need for rescue oral corticosteroids or hospital admission compared to the same or an increased dose of ICS in children and adolescents with mild to moderate asthma. Although anti-leukotrienes have been licensed for use in children for over 10 years, the paucity of paediatric trials, the absence of data on preschoolers, and the variability in the reporting of relevant clinical outcomes considerably limit firm conclusions. At present, there is no firm evidence to support the efficacy and safety of anti-leukotrienes as add-on therapy to ICS as a step-3 option in the therapeutic arsenal for children with uncontrolled asthma symptoms on low-dose ICS.


Effect of Patent Foramen Ovale Closure After Stroke on Circulatory Biomarkers.
To determine the influence of patent foramen ovale (PFO) closure on circulatory biomarkers. Consecutive patients with PFO-related stroke were prospectively enrolled and followed with serial sampling of cardiac atrial and venous blood pre- and post-PFO closure over time. Candidate biomarkers were identified by mass spectrometry in a discovery cohort first, and lead candidates were validated in an independent cohort. Patients with PFO-related stroke (n = 254) were recruited and followed up to 4 years (median 2.01; interquartile range 0.77-2.54). Metabolite profiling in the discovery cohort (n = 12) identified homocysteine as the most significantly decreased factor in intracardiac plasma after PFO closure (false discovery rate 0.001). This was confirmed in a validation cohort (n = 181), where intracardiac total homocysteine (tHcy) was immediately reduced in patients with complete closure, but not in those with residual shunting, suggesting association of PFO shunting with tHcy elevation (β 0.115; 95% confidence interval [CI] 0.047-0.183; p = 0.001). tHcy reduction was more dramatic in left atrium than right (p < 0.001), suggesting clearance through pulmonary circulation. Long-term effect of PFO closure was also monitored and compared to medical treatment alone (n = 61). Complete PFO closure resulted in long-term tHcy reduction in peripheral blood, whereas medical therapy alone showed no effect (β -0.208; 95% CI -0.375∼-0.058; p = 0.007). Residual shunting was again independently associated with persistently elevated tHcy (β 0.184; 95% CI 0.051-0.316; p = 0.007). PFO shunting may contribute to circulatory tHcy elevation, which is renormalized by PFO closure. PFO is not just a door for clots, but may itself enhance clot formation and injure neurovasculature by clot-independent mechanisms. Biomarkers such as tHcy can potentially serve as cost-effective measures of residual shunting and neurovascular risk for PFO stroke.


Extragastrointestinal stromal tumor mimicking a uterine tumor. A rare clinical entity.
Gastrointestinal stromal tumors are the most common mesenchymal tumors of the gastrointestinal tract. These tumors are present in almost all case mutations of KIT-CD117. When located in different places other than the gastrointestinal tract they are called extragastrointestinal stromal tumors (EGISTs). We present the case of a 70-year old patient with abdominal pain. Computed tomography (C/T) and ultrasound (U/S) indicated the existence of a hypoechoic enlarged 9.6 x 10 cm uterus due to leiomyoma. The clinical condition of the patient deteriorated and obtained the characteristics of an acute abdomen. The patient underwent urgent exploratory laparotomy, which revealed the incidental existence of a large tumorous formation in the pouch of Douglas. A total abdominal hysterectomy, bilateral ovarectomy, omentectomy, and tumor resection from the rectouterine pouch were performed. Histology analysis confirmed the diagnosis of a malignant EGIST. EGISTs are infrequent in pelvis. In our case, pelvic EGIST led to an acute pain symptomatology obtaining characteristics of invasive uterine leiomyosarcoma. Pelvic imaging with classical methods of U/S and C/T may lead to confusion and false diagnosis. To the best of our knowledge, this is the first case report about an EGIST located in the rectouterine pouch of Douglas leading to acute abdomen symptomatology.


Reward and the serotonergic system.
Anhedonia, as a failure to experience rewarding stimuli, is a key characteristic of many psychiatric disorders including depression and schizophrenia. Investigations on the neurobiological correlates of reward and hedonia/anhedonia have been a growing subject of research demonstrating several neuromodulators to mediate different aspects of reward processing. Whereas the majority of research on reward mainly focused on the dopamine and opioid systems, a serotonergic mechanism has been neglected. However, recent promising results strengthen the pivotal role of serotonin in reward processing. Evidence includes electrophysical and pharmacological as well as genetic and imaging studies. Primate research using single-unit recording of neurons within the dorsal raphe nucleus argues for a serotonergic mediation of reward value, whereas studies using intracranial self-stimulation point to an important contribution of serotonin in modulating motivational aspects of rewarding brain stimulation. Pharmacological studies using agonists and antagonists of serotonergic receptor subtypes and approaches investigating an increase or decrease of the extracellular level of serotonin offer strong evidence for a serotonergic mediation, ranging from aversion to pleasure. This review provides an argument for serotonin as a fundamental mediator of emotional, motivational and cognitive aspects of reward representation, which makes it possibly as important as dopamine for reward processing.


An Ethical Analysis of Hospital Visitor Restrictions and Masking Requirements During the COVID-19 Pandemic
Nonpharmaceutical interventions to minimize the transmission of the severe acute respiratory syndrome coronavirus 2 are necessary because we currently lack a vaccine or specific treatments. Healthcare facilities have adopted visitor restrictions and masking requirements. These interventions should be evaluated as public health measures, focusing on their efficacy, the availability of less-restrictive alternatives, and the minimization of the burdens and their balance with the benefits. These interventions, as well as exceptions, can be justified by the same analysis. For example, visitor restrictions are sound, as are exceptions for women in labor, adults with disabilities, minor children, and individuals who are dying. In implementing these policies, specific rules are preferable to general principles because they are more efficient and reduce possible bias. There should, however, be appeal mechanisms and retrospective review processes. Evaluating requests for medical exemptions to masking requirements is particularly difficult, given the prevalence of nonmedical objections, false claims of medical exemptions, and a lack of objective medical criteria. Requiring written statements by licensed healthcare providers that undergo subsequent substantive review may therefore be justified.


Characteristics of the hemostatic action of KFA-1411, an inhibitor of coagulation factor Xa (FXa), in humans and various animals.
This study examined a low-molecular-weight factor-Xa inhibitor, KFA-1411 (3-[N-(3-amidinophenyl)-N-[N-[4-[1-(1-iminoethyl)piperidin-4- yl]phenyl]carbamoylmethyl]aminomethyl]phenoxyacetic acid monosulfonate-dihydrate). KFA-1411 selectively inhibited FXa among the serine proteases in the human blood-coagulation cascade with a Ki value of 1.73 nM, (selectivity ratio, 15000 versus its action on thrombin). The anticoagulant action of KFA-1411 in human plasma almost equaled that of the selective thrombin inhibitor, argatroban. KFA-1411 did not inhibit platelet aggregation at the concentration at which it showed an anticoagulant action. In contrast, argatroban, heparin, and low-molecular-weight heparin (LMWH; dalteparin) inhibited thrombin-induced platelet aggregation at concentrations lower than those needed for their anticoagulant actions. The FXa-inhibiting action of KFA-1411 differed among animal species, the maximum effect being seen in humans, followed by monkeys and rabbits, with rats and mice showing about one-tenth the potency seen in humans. A species variation was also observed among the values obtained for KFA-1411 in respect of anticoagulant activity in plasma (monkeys again being closest to humans). These results indicate that KFA-1411 may exhibit antithrombotic efficacy without an unwanted platelet-related action in the future treatment of various thrombotic diseases. The experimental model of monkeys is recommended for estimation of the clinical effects and safety of KFA-1411 in humans.


Comparison of monounsaturated fatty acids and carbohydrates for lowering plasma cholesterol.
To examine the effects of dietary fatty acids and carbohydrate on plasma lipids and lipoproteins, 11 patients with a mean plasma total cholesterol level of 251 +/- 10 mg per deciliter were studied on a metabolic ward during three dietary periods, each lasting four weeks. A liquid diet rich in monounsaturated fatty acids ("High-Mono") and a diet low in fat ("Low-Fat") were compared with a diet high in saturated fatty acids ("High-Sat"). The High-Sat and High-Mono diets contained 40 percent of their total calories as fat and 43 percent as carbohydrate; the Low-Fat diet had 20 percent fat and 63 percent carbohydrate. Body weight was kept constant by adjusting total caloric intake. As compared with the High-Sat diet, both the High-Mono and Low-Fat diets lowered plasma total cholesterol (by 13 percent and 8 percent, respectively) and low-density lipoprotein cholesterol (by 21 percent and 15 percent, respectively). As compared with the High-Sat diet, the Low-Fat diet raised triglyceride levels and significantly reduced plasma high-density lipoprotein cholesterol. In contrast, the High-Mono diet had no effect on levels of triglycerides or high-density lipoprotein cholesterol. The ratio of low-density to high-density lipoprotein cholesterol was also significantly lower when the High-Mono diet rather than the Low-Fat diet was followed. Therefore, in short-term studies in which liquid diets are used and body weight is kept constant, a diet rich in monounsaturated fatty acids appears to be at least as effective in lowering plasma cholesterol as a diet low in fat and high in carbohydrate.


Stimulus-induced dissociation of neuronal firing rates and local field potential gamma power and its relationship to the resonance blood oxygen level-dependent signal in macaque primary visual cortex.
The functional magnetic resonance imaging (fMRI) blood oxygenation level-dependent (BOLD) signal is regularly used to assign neuronal activity to cognitive function. Recent analyses have shown that the local field potential (LFP) gamma power is a better predictor of the fMRI BOLD signal than spiking activity. However, LFP gamma power and spiking activity are usually correlated, clouding the analysis of the neural basis of the BOLD signal. We show that changes in LFP gamma power and spiking activity in the primary visual cortex (V1) of the awake primate can be dissociated by using grating and plaid pattern stimuli, which differentially engage surround suppression and cross-orientation inhibition/facilitation within and between cortical columns. Grating presentation yielded substantial V1 LFP gamma frequency oscillations and significant multi-unit activity. Plaid pattern presentation significantly reduced the LFP gamma power while increasing population multi-unit activity. The fMRI BOLD activity followed the LFP gamma power changes, not the multi-unit activity. Inference of neuronal activity from the fMRI BOLD signal thus requires detailed a priori knowledge of how different stimuli or tasks activate the cortical network.


Osteopathic vs. chiropractic education: a student perspective.
This study compares nationwide survey results from 506 second year students of 11 osteopathic schools and 881 students from the first and second academic year (third term/fourth quarter) of eight chiropractic colleges. Each student was given a questionnaire regarding his/her perspective on the education he/she was receiving. Both populations were questioned about whether or not they came from an osteopathic/chiropractic family, their application process, the efficacy of osteopathic manipulative therapy (OMT)/chiropractic adjustments, their first year attitude concerning the efficacy of OMT/chiropractic adjustments, the integration of osteopathic/chiropractic principles into the curriculum and the justification for separate health care professions. Osteopathic and chiropractic students entered their respective professions from nonosteopathic/non-chiropractic families. Although both populations selected their profession as a first and primary choice, chiropractic students were more substantially represented. Upon entering their program, osteopathic students were not convinced, but had an open mind concerning the effectiveness of osteopathic manipulative therapy (OMT), and were divided as to whether there is enough of a distinction between DOs and MDs to justify separate professions. Chiropractic students, on the other hand, entered their program convinced that chiropractic adjustments are effective, and saw a clear distinction between the roles of chiropractic physicians and medical doctors.


Takotsubo cardiomyopathy: real life management in the intensive coronary care unit.
Takotsubo cardiomyopathy is a cardiac syndrome characterized by reversible left ventricular dysfunction, ischemic changes on electrocardiogram, elevation of cardiac biomarkers, absence of obstructive coronary artery disease in the setting of various stressing conditions. To date, little is known on best clinical management of this syndrome in coronary care units. Whe thus aimed to present our experience in a real life takotsubo population. We identified all patients with Takotsubo cardiomyopathy at our center Maria Vittoria Hospital, Turin, between October 2006 and February 2012. Patients where considered to have Takotsubo syndrome if they presented chest pain on admission, new elettrocardiographic changes suggestive of myocardial ischemia, evidence of apical balloning with hyperkinesis of basal segments on echocardiography, rise in troponin I and, after coronary angiography, no coronary artery disease. We adjudicated the following clinical events: death and recurrence of ischemic events; we also made a detailed analysis of the stressing conditions leading to clinical syndrome. A total of 26 patients were included, 4 (15%) males and 22 (85%) females; mean age was 71±13. After more than 1 year median follow-up the incidence of death was 7.7% (2 deaths), with all deaths, due to cardiogenic shock, occurring in the first 10 days of hospitalization; 2 patients (8%) experienced recurrence of ischemic event. Leading cause of Takostubo was major depressive episode (16%), followed by mourning (12%), falling down with difficulties in standing up (12%), vomiting (8%) and pulmonary infection (8%). In the coronary care unit major complications of patients with Takotsubo syndrome were acute hearth failure (62%), cardiogenic shock (27%), sepsis (31%), pulmonary aedema (27%) and anemia (12%). Two patients needed non-invasive ventilation support and one intra-aortic balloon conterpulasation. In addition one patient developed rabdomyolysis and one left heart thrombus. Cornerstone drug therapy was as follows: 96% of patients took aspirin, 58% beta blockers, 54% nitroglicerine, 46% intravenous heparin, 27% dopamine. Takotsubo syndrome is an important safety issue occurring predominantly in post-menopausal women undergoing specific stressing condition. Heart failure and cardiogenic shock are the most serious clinical complication and leading cause of death in the short period, good prognosis is seen thereafter.


Evaluation of role of oxidative stress on aging in Caenorhabditis elegans: a brief review.
Recently the relationship between oxidative stress and aging has been brought into question. It has been suggested that while oxidative events may play a role in the progression of age-related pathologies, it is not relevant to aging processes not involving specific diseases associated with senescence. The evidence in support of this concept is largely based on studies with the roundworm, Caenorhabditis elegans (C. elegans) that has been extensively used as a model system to study aging. This commentary evaluates data derived from C. elegans and documents that the preponderance of evidence from this species supports the role of pro-oxidant events as being a significant contributor to normal aging. Possible reasons for some anomalous findings conflicting with this concept, are discussed.


Lone and lonely in a double ambivalence situation as experienced by callers while waiting for the ambulance in a rural environment.
In a rural environment where distances and access to ambulance resources in people's immediate area are limited, other responders like firefighters dispatched to perform a first aid before ambulance arrives in areas where a longer response time exists; an assignment called 'While Waiting for the Ambulance' (WWFA). Knowledge is limited about the experience from a caller's perspective when a person has a life-threatening condition needing emergency help and both firefighters in a WWFA assignment and ambulance staff are involved. The aim of the study is to describe the emergency situation involving a WWFA assignment in a rural environment from the caller's perspective. A descriptive design using qualitative methodology with a reflective lifeworld research (RLR) approach was used for this study, including in-depth interviews with eight callers. An emergency situation involving WWFA assignment in a rural environment mean a sense of being lone and lonely with a vulnerability in while waiting to hand over responsibility for the affected person. Ambivalence in several dimensions arises with simultaneous and conflicting emotions. A tension between powerlessness and power of action where the throw between doubt and hope are abrupt with a simultaneous pendulum between being in a chaos and in a calm. A double ambivalence emerges between, on one hand feeling alone in the situation and having full control, on the other hand, with trust handing over the responsibility, thereby losing control. Contact with the emergency medical dispatcher becomes a saving lifeline to hold onto, and access to emergency help in the immediate area of WWFA is valuable and important. Trust and confidence are experienced when callers are met with empathy, regardless of personal acquaintance with arriving responders.


Management of a urethral tear with porcine small intestinal submucosa-augmented urethroplasty and balloon dilation for subsequent urethral stricture in a cat.
As a result of vehicular trauma, a 3-year-old neutered male domestic shorthair cat sustained luxation of the sacrocaudal joint and a urethral tear. Retrograde contrast urethrocystography revealed a urethral tear at the level of the ischiatic tuberosity. Conservative treatment for 7 days with a urethral catheter was unsuccessful. An approach for a perineal urethrostomy was performed and revealed a large urethral tear (4 mm in length in a craniocaudal orientation and encompassing approx 50% of the urethral circumference) proximal to the bulbourethral glands. Urethroplasty was performed with a graft of a rectangular section of single-layer porcine small intestinal submucosa. Perineal urethrostomy was then completed routinely, and a urethral catheter was left in place for 5 days. Two days after removal of the urethral catheter, stranguria was noted. Retrograde contrast urethrocystography revealed a urethral stricture. Balloon dilation of the urethral stricture was performed, and the cat's stranguria improved. Ten weeks following balloon dilation, the cat developed hematuria, and a urinary tract infection and urethral stricture were diagnosed. Balloon dilation was repeated with instillation of triamcinolone solution at the stricture site. Eighteen months later (approx 21 months after the initial surgery), the cat was urinating normally. The outcome for the cat of this report indicated that porcine small intestinal submucosa may be used to successfully augment urethroplasty for treatment of traumatic urethral tears in cats. Urethral balloon dilation with triamcinolone instillation may be used to treat postoperative urethral strictures.


The housing/health relationship: what do we know?
Research into the relationship between housing and health has frequently been narrowly focused, fragmented, and of marginal practical relevance to either housing or health policy. From an extensive review of the literature, this paper reports on the current state of knowledge about the relationship between housing and health. The research falls into four distinct categories: (1) specific physical or chemical exposures; (2) specific biological exposures; (3) physical characteristics of the house; and (4) social, economic, and cultural characteristics of housing. Much of the general literature on the effects of housing on health cites previous studies and then proceeds to advocate housing policies and strategies that are aimed at improving population health. Studies providing original data on the relationship, which is the vast majority of the literature, focus on very specific physical, chemical, and biological exposures with a known or suspected effect on health within the house, or they focus on the social, economic, and cultural characteristics of the house. The mechanisms through which specific aspects of housing affect health are extremely complicated, but they do exist. Researchers have made a great deal of progress in clarifying some of these mechanisms. A large gap still exists in our knowledge about the links and pathways between housing, socio-economic status and health status.


A novel fortified blended flour, corn-soy blend "plus-plus," is not inferior to lipid-based ready-to-use supplementary foods for the treatment of moderate acute malnutrition in Malawian children.
Children with moderate acute malnutrition (MAM) are often treated with fortified blended flours, most commonly a corn-soy blend (CSB). However, recovery rates remain <75%, lower than the rate achieved with peanut paste-based ready-to-use supplementary foods (RUSFs). To bridge this gap, a novel CSB recipe fortified with oil and dry skim milk, "CSB++," has been developed. In this trial we compared CSB++ with 2 RUSF products for the treatment of MAM to test the hypothesis that the recovery rate achieved with CSB++ will not be >5% worse than that achieved with either RUSF. We conducted a prospective, randomized, investigator-blinded, controlled noninferiority trial involving rural Malawian children aged 6-59 mo with MAM. Children received 75 kcal CSB++ · kg(-1) · d(-1), locally produced soy RUSF, or an imported soy/whey RUSF for ≤12 wk. The recovery rate for CSB++ (n = 763 of 888; 85.9%) was similar to that for soy RUSF (795 of 806, 87.7%; risk difference: -1.82%; 95% CI: -4.95%, 1.30%) and soy/whey RUSF (807 of 918, 87.9%; risk difference: -1.99%; 95% CI: -5.10%, 1.13%). On average, children who received CSB++ required 2 d longer to recover, and the rate of weight gain was less than that with either RUSF, although height gain was the same among all 3 foods studied. A novel, locally produced, fortified blended flour (CSB++) was not inferior to a locally produced soy RUSF and an imported soy/whey RUSF in facilitating recovery from MAM. The recovery rate observed for CSB++ was higher than that for any other fortified blended flour tested previously. This trial is registered at clinicaltrials.gov as NCT00998517.


Gabapentin premedication for postoperative analgesia and emergence agitation after sevoflurane anesthesia in pediatric patients.
The aim of this study was to investigate the effect of gabapentin premedication on postoperative 24th hour total analgesic consumption and the incidence of emergence agitation after sevoflurane based anesthesia in pediatric patients undergoingtonsillectomyandadenoidectomy. 46 healthy, ASA class I or II, aged 3-12 year old children were included into the study. The patients were randomly assigned to one of the control (Group C) or gabapentin group (Group G) consisting of 23 patients in each. Group C received 10 ml of saline, Group G received gabapentin 15 mg.kg-1 dissolved in 10 ml of saline orally 30 min. before the induction of anesthesia. After anesthesia induction with 8% sevoflurane in 50% O2-N2O. General anesthesia was maintained with 1 MAC sevoflurane in 50% O2-N2O. Emergence agitation was assessed with a 5 point scale and recorded every 10 min. of first 30 min. of the postoperative period. Parents were contacted 24 hours after the surgery to evaluate pain, total analgesic consumption, parent satisfactionandanysideeffect. Agitation scores were significantly lower in group G compared to group C in the postoperative 20th and 30th minutes (p<0.01, 0.05 respectively). Total analgesic requirement in postoperative 24 hour was significantly lower in group G (p<0.01). Satisfaction scores of parents was also higher in group G (p<0.05). Gabapentin premedication decreases postoperative 24th hour analgesic consumption and attenuates emergence agitation after sevoflurane anesthesia.


New clinical application prospects of artemisinin and its derivatives: a scoping review.
Recent research has suggested that artemisinin and its derivatives may have therapeutic effects on parasites, viruses, tumors, inflammation and skin diseases. This study aimed to review clinical research on artemisinin and its derivatives except anti-malaria and explore possible priority areas for future development. Relevant articles in English and Chinese published before 28 October 2021 were reviewed. All articles were retrieved and obtained from databases including WanFang, PubMed/MEDLINE, the Cochrane Library, China National Knowledge International, Embase, OpenGrey, the Grey Literature Report, Grey Horizon, and ClinicalTrials.gov. Studies were selected for final inclusion based on predefined criteria. Information was then extracted and analyzed by region, disease, outcome, and time to identify relevant knowledge gaps. Seventy-seven studies on anti-parasitic (35), anti-tumor (16), anti-inflammatory (12), anti-viral (8), and dermatological treatments (7) focused on the safety and efficacy of artemisinin and its derivatives. The anti-parasitic clinical research developed rapidly, with a large number of trials, rapid clinical progress, and multiple research topics. In contrast, anti-viral research was limited and mainly stayed in phase I clinical trials (37.50%). Most of the studies were conducted in Asia (60%), followed by Africa (27%), Europe (8%), and the Americas (5%). Anti-parasite and anti-inflammatory research were mainly distributed in less developed continents such as Asia and Africa, while cutting-edge research such as anti-tumor has attracted more attention in Europe and the United States. At the safety level, 58 articles mentioned the adverse reactions of artemisinin and its derivatives, with only one study showing a Grade 3 adverse event, while the other studies did not show any related adverse reactions or required discontinuation. Most studies have discovered therapeutic effects of artemisinin or its derivatives on anti-parasitic (27), anti-tumor (9), anti-inflammatory (9) and dermatological treatment (6). However, the efficacy of artemisinin-based combination therapies (ACTs) for parasitic diseases (non-malaria) is still controversial. Recent clinical studies suggest that artemisinin and its derivatives may be safe and effective candidates for anti-tumor, anti-parasitic, anti-inflammatory and dermatological drugs. More phase II/III clinical trials of artemisinin and its derivatives on antiviral effects are needed.


[The international language of science].
There is a trend, with a view to achieving greater scientific visibility and international projection, that favors the adoption of the English language in Brazilian journals dealing with nosological problems. This argument is here questioned. Latin America is a large continent with characteristic health problems. Thus it is to be recommended that scientific public health journals should accept for publication papers written in the three main language: English, Portuguese and Spanish.


Accelerometer-determined steps per day in US adults.
The 2005-2006 National Health and Nutrition Examination Survey (NHANES) released, for the first time, the ActiGraph AM-7164 accelerometer-defined step data in addition to time in intensity (defined by activity counts). This accelerometer is known to have a lower sensitivity threshold than accepted pedometers, leading to relatively higher step estimates. The purpose of this analysis is to provide the population- and sex-specific epidemiology of accelerometer-determined steps per day with and without censoring steps detected at the lowest end of the activity spectrum (i.e., inactivity). The analysis sample represents 3744 participants > or =20 yr who had at least one valid day (i.e., at least 10 h) of monitoring. Means (SE) for steps per day were computed using all steps (i.e., uncensored) and again after censoring those steps taken at an intensity <500 activity counts per minute (indicative of inactivity intensity). On average, US adults took 9676 +/- 107 uncensored steps per day or 6540 +/- 106 censored steps per day. The results of this nationally representative survey indicate that US adults take approximately 10,000 uncensored accelerometer-determined steps per day, which is improbable considering other studies of free-living physical activity in the United States. Until a more valid conversion factor is ascertained for translating accelerometer and pedometer-determined steps, our use of the <500 activity count per minute threshold holds considerable merit.


DOE Optimization of Nano-based Carrier of Pregabalin as Hydrogel: New Therapeutic &Chemometric Approaches for Controlled Drug Delivery Systems.
Niosomes entrapping pregabalin (PG) were prepared using span 60 and cholesterol in different molar ratios by hydration method, the remaining PG from the hydrating solution was separated from vesicles by freeze centrifugation. Optimization of nano-based carrier of pregabalin (PG) was achieved. Quality by Design strategy was successfully employed to obtain PG-loaded niosomes with the desired properties. The optimal particle size, drug release and entrapment efficiency were attained by Minitab® program using design of experiment (DOE) that predicted the best parameters by investigating the combined effect of different factors simultaneously. Pareto chart was used in the screening step to exclude the insignificant variables while response surface methodology (RSM) was used in the optimization step to study the significant factors. Best formula was selected to prepare topical hydrogels loaded with niosomal PG using HPMC and Carbopol 934. It was verified, by means of mechanical and rheological tests, that addition of the vesicles to the gel matrix affected significantly gel network. In vitro release and ex vivo permeation experiments were carried out. Delivery of PG molecules followed a Higuchi, non Fickian diffusion. The present work will be of interest for pharmaceutical industry as a controlled transdermal alternative to the conventional oral route.


Prognostic value of EGF receptor and tumor cell proliferation in bladder cancer: therapeutic implications.
Changes in growth factor receptor expression may confer a growth advantage on tumour cells. Epidermal growth factor-receptor (EGF-R) has been associated with the genesis of bladder tumours. We sought a link between EGF-R expression and MIB-1 cell proliferation and examined their prognostic value in the progression of bladder cancer. Fresh frozen samples from 113 transitional cell carcinomas (TCC) of the bladder and 10 healthy bladders were studied by immunohistochemistry, using monoclonal antibodies for EGF-R expression and MIB-1 for cell proliferation. Qualitative and quantitative immunostaining were analyzed in relation to time to progression and compared with clinical and pathologic parameters for prognostic significance in univariate and multivariate analysis (stepwise logistic regression). EGF-R stained more intensively in invasive tumours. Median nuclear over-expression of MIB-1 was 28%. Progression free survival rate estimates (log rank test) were significantly lower in patients EGF-R positive and with MIB-1 score above 28% (P < 0.0001, P < 0.0001, respectively). Multivariate analysis indicated that MIB-1 immunostaining was the most significant independent variable and EGF-R expression had no additional prognostic value over clinical stage and grade and cell proliferation. The MIB-1 proliferation index is a stronger predictor of bladder tumour progression than is EGF-R over-expression. This marker yield significant prognostic information in addition to stage and grade and may be of value for the clinical management of superficial and invasive bladder carcinomas. The pattern of EGF-R immunostaining and its association with tumour progression makes it a candidate for antigrowth factor therapy.


Imbalanced production of IL-18 and its antagonist in human diseases, and its implications for HIV-1 infection.
IL-18 is a pleiotropic and multifunctional cytokine that belongs to the IL-1 family. It is produced as a biologically inactive precursor, which is cleaved into its active mature form mainly by caspase-1. The caspase becomes active from its inactive precursor (procaspase-1) upon assembly of an inflammasome. Because of IL-18's potential pro-inflammatory and tissue destructive effects, its biological activities are tightly controlled in the body by its naturally occurring antagonist called IL-18BP. The antagonist is produced in the body both constitutively and in response to an increased production of IL-18 as a negative feedback mechanism. Under physiological conditions, most of IL-18 in the circulation is bound with IL-18BP and is inactive. However, an imbalance in the production of IL-18 and its antagonist (an increase in the production of IL-18 with a decrease, no increase or an insufficient increase in the production of IL-18BP) has been described in many chronic inflammatory diseases in humans. The imbalance results in an increase in the concentrations of free IL-18 (unbound with its antagonist) resulting in increased biological activities of the cytokine that contribute towards pathogenesis of the disease. In this article, we provide an overview of the current biology of IL-18 and its antagonist, discuss how the imbalance occurs in HIV infections and how it contributes towards development of AIDS and other non-AIDS-associated clinical conditions occurring in HIV-infected individuals undergoing combination anti-retroviral therapy (cART). Finally, we discuss challenges facing immunotherapeutic strategies aimed at restoring balance between IL-18 and its antagonist in these patients.


Thermal scanning probe lithography for the directed self-assembly of block copolymers.
Thermal scanning probe lithography (t-SPL) is applied to the fabrication of chemical guiding patterns for directed self-assembly (DSA) of block copolymers (BCP). The two key steps of the overall process are the accurate patterning of a poly(phthalaldehyde) resist layer of only 3.5 nm thickness, and the subsequent oxygen-plasma functionalization of an underlying neutral poly(styrene-random-methyl methacrylate) brush layer. We demonstrate that this method allows one to obtain aligned line/space patterns of poly(styrene-block-methyl methacrylate) BCP of 18.5 and 11.7 nm half-pitch. Defect-free alignment has been demonstrated over areas of tens of square micrometres. The main advantages of t-SPL are the absence of proximity effects, which enables the realization of patterns with 10 nm resolution, and its compatibility with standard DSA methods. In the brush activation step by oxygen-plasma exposure, we observe swelling of the brush. This effect is discussed in terms of the chemical reactions occurring in the exposed areas. Our results show that t-SPL can be a suitable method for research activities in the field of DSA, in particular for low-pitch, high-χ BCP to achieve sub-10 nm line/space patterns.


Zebrafish crypt neurons project to a single, identified mediodorsal glomerulus.
Crypt neurons are a third type of olfactory receptor neurons with a highly unusual "one cell type--one receptor" mode of expression, the same receptor being expressed by the entire population of crypt neurons. Attempts to identify the target region(s) of crypt neurons have been inconclusive so far. We report that TrkA-like immunoreactivity specifically labeled somata, axons, and terminals of zebrafish crypt neurons and reveal a single glomerulus, mdg2 of the dorsomedial group, as target glomerulus of crypt neurons. Injection of a fluorescent tracing dye into the mdg2 glomerulus retrogradely labeled mostly crypt neurons, as assessed by quantitative morphometry, whereas no crypt neurons were found after injections in neighboring glomeruli. Our data provide strong evidence that crypt neurons converge onto a single glomerulus, and thus form a labeled line consisting of a single sensory cell type, a single olfactory receptor and a single target glomerulus.


Evaluating third- and fourth-year veterinary students' communication skills knowledge and performance at Colorado State University.
To assess the impact of a communication program on a cohort of veterinary students' knowledge and performance of communication skills. Class cohort of veterinary students at Colorado State University. Year 3 students' knowledge of communication skills was evaluated using quizzes, administered before and after the fall 2016 and spring 2017 Clinical Communication Skills-I and II junior practicum. In year 4, student performance of 22 Calgary-Cambridge Guide communication skills was assessed by coding video-recordings of student-client interactions collected during their second and fourth weeks of the Community Practice rotation in the summer and fall of 2017 and spring of 2018. The impact of training, association with demographic factors, and correlation between knowledge and performance of communication skills were investigated. In year 3, 136 students completed both fall and spring quizzes; in year 4, 65 week-2 and 29 week-4 appointments were video-recorded during Community Practice rotation. Students' knowledge assessed via quizzes containing skill spotting and skill demonstrating questions increased significantly after the fall and spring junior practicums; however, knowledge of communication skills was not associated with performance during year 4 Community Practice rotations. Communication skills most frequently demonstrated by students during the fourth year Community Practice rotation were open-ended questions, closed-ended questions, empathy toward the client and patient, providing "chunks" of information, and signposting. Students received high quality scores for non-verbal behaviors and logical clinical interview structure. Results suggest that experiential learning techniques, including a flipped classroom approach, role-play, and communication laboratories contributed to increased student knowledge of communication skills.


Inhibition of proliferation of prostate cancer cells by a 19-nor-hexafluoride vitamin D3 analogue involves the induction of p21waf1, p27kip1 and E-cadherin.
We have synthesized and studied the ability of a series of seven novel 1 alpha,25(OH)2 vitamin D3 analogues to inhibit clonal growth of prostate cancer cells (LNCaP, PC-3 and DU-145). Addition of double and triple bonds to the C/D ring (C-16) and side chain (C-22 and C-23) as well as lengthening of the side chain were important for enhanced activity against LNCaP and PC-3. Reorientation of the side chain in the 20-epi configuration resulted in analogues that were extremely potent only against LNCaP (ED50 approximately 5 x 10(-11) M). Compounds with six fluorines on the end of the side chain were very active against both PC-3 and LNCaP (ED50 approximately 2 x 10(-8) M). DU-145 cells were relatively resistant to compounds with all of these modifications, but removal of C-19 (e.g. 1,25(OH)2-16-ene-23-yne-26,27-F6-19-nor-D3) resulted in an analogue that was inhibitory against all three prostate cell lines. Further analysis showed that pulse exposure (3 days, 10(-7) M) to this analogue was enough to inhibit clonal growth of PC-3 cells by 50%. The same exposure also induced cell cycle arrest of all three cell lines, accompanied by upregulated protein expression of the cyclin-dependent kinase inhibitor (CDKI) known as p21waf1 in all three cell lines, and the CDKI known as p27kip1 in LNCaP cells. Associated with upregulation of these CDKIs, partial differentiation occurred as measured by increased expression of both prostate-specific antigen by LNCaP cells and E-cadherin, a cell adhesion protein that may act as a putative tumour suppressor (LNCaP and PC-3 cells). In summary, this is the first report of a potent series of 19-nor-vitamin D3 analogues with the ability to inhibit proliferation of LNCaP, PC-3 and DU-145 prostate cancer cell lines. These compounds may mediate their potent anti-proliferative activities through a cell cycle arrest pathway.


Identification and Prevention of Secondary Heart Failure: A Case Study.
Heart failure, a complex clinical syndrome affecting millions of Americans, is associated with high morbidity and mortality and a significant financial burden on the health care system. Recent health care reform efforts have focused on reducing 30-day heart failure hospital readmissions, increasing the cost-effectiveness of care provided to heart failure patients, and improving health outcomes for these patients. This case report describes an acutely ill patient with multiple comorbidities who was not initially admitted for heart failure but who developed acute decompensated heart failure during his hospital stay. The purpose of this in-depth analysis is to discuss the role of bedside nurses and advanced practice nurses in managing heart failure, describe the challenges of identifying secondary heart failure in patients with complex conditions, and suggest methods of improving health-related outcomes to prevent hospital readmissions.


Characterization of a 140-kD avian cell surface antigen as a fibronectin-binding molecule.
A 140,000-D protein cell surface antigen (140k) complex has been implicated in fibronectin-mediated cell-substratum attachment. We have used three different experimental systems to evaluate the hypothesis that this 140k complex can function as a fibronectin receptor. A monoclonal antibody that binds to the 140k complex specifically inhibits the direct binding of 3H-labeled 75,000-D fibronectin cell-binding fragment (f75k) to chicken embryo fibroblasts in suspension. The 140k complex is retarded in its passage through an affinity column consisting of immobilized f75k, and this interaction is specifically inhibited by a synthetic peptide that contains the fibronectin cell-recognition signal sequence. Finally, exogenous purified 140k complex inhibits the attachment and spreading of chicken embryo fibroblasts on fibronectin-coated substrates. Thus, our results indicate that the 140k complex can bind directly to fibronectin and is likely to be a fibronectin receptor for chicken cells.


Effect of specific trinitrophenylation of the lysine epsilon amino group of glucagon on receptor binding and adenylate cyclase activation.
The trinitrophenyl group was specifically introduced into the epsilon-amino group of glucagon by reaction of N alpha-citraconyl glucagon with trinitrobenzenesulfonic acid. The N alpha-citraconyl blocking group was subsequently removed by acid treatment yielding N epsilon-trinitrophenyl glucagon which was purified by anion-exchange chromatography. The derivative showed less secondary structure as measured by circular dichroism than the native hormone at pH 8.0 and at pH 2.0 in the presence of sodium dodecyl sulfate. The analog possessed 4-5% the potency of glucagon in stimulating adenylate cyclase with 90% maximal stimulation and possessed 30% the potency of glucagon in competing for glucagon-specific receptor sites in hepatic plasma membranes. Although the structure of N epsilon-trinitrophenyl glucagon is very similar to N epsilon-4-azido-2-nitrophenyl glucagon, the photoaffinity antagonist synthesized by M.D. Bregman and D. Levy [(1977) Biochem. Biophys. Res. Commun. 78, 584-590.], the biological activities of the two are different. Possible explanations for these differences are discussed.


MOLECULAR EVOLUTION OF GLUTAMINE SYNTHETASE II AND III IN THE CHROMALVEOLATES(1).
Glutamine synthetase (GS) is encoded by three distinct gene families (GSI, GSII, and GSIII) that are broadly distributed among the three domains of life. Previous studies established that GSII and GSIII isoenzymes were expressed in diatoms; however, less is known about the distribution and evolution of the gene families in other chromalveolate lineages. Thus, GSII cDNA sequences were isolated from three cryptophytes (Guillardia theta D. R. A. Hill et Wetherbee, Cryptomonas phaseolus Skuja, and Pyrenomonas helgolandii Santore), and GSIII was sequenced from G. theta. Red algal GSII sequences were obtained from Bangia atropurpurea (Mertens ex Roth) C. Agardh; Compsopogon caeruleus (Balbis ex C. Agardh) Mont.; Flintiella sanguinaria F. D. Ott and Porphyridium aerugineum Geitler; Rhodella violacea (Kornmann) Wehrmeyer and Dixoniella grisea (Geitler) J. L. Scott, S. T. Broadwater, B. D. Saunders, J. P. Thomas et P. W. Gabrielson; and Stylonema alsidii (Zanardini) K. M. Drew. In Bayesian inference and maximum-likelihood (ML) phylogenetic analyses, chromalveolate GSII sequences formed a weakly supported clade that nested among sequences from glaucophytes, red algae, green algae, and plants. Red algal GSII sequences formed two distinct clades. The largest clade contained representatives from the Cyanidiophytina and Rhodophytina and grouped with plants and green algae. The smaller clade (C. caeruleus, Porphyra yezoensis, and S. alsidii) nested within the chromalveolates, although its placement was unresolved. Chromalveolate GSIII sequences formed a well-supported clade in Bayesian and ML phylogenies, and mitochondrial transit peptides were identified in many of the sequences. There was strong support for a stramenopile-haptophyte-cryptophyte GSIII clade in which the cryptophyte sequence diverged from the deepest node. Overall, the evolutionary history of the GS gene families within the algae is complex with evidence for the presence of orthologous and paralogous sequences, ancient and recent gene duplications, gene losses and replacements, and the potential for both endosymbiotic and lateral gene transfers.


Towards an integrated food safety surveillance system: a simulation study to explore the potential of combining genomic and epidemiological metadata.
Foodborne infection is a result of exposure to complex, dynamic food systems. The efficiency of foodborne infection is driven by ongoing shifts in genetic machinery. Next-generation sequencing technologies can provide high-fidelity data about the genetics of a pathogen. However, food safety surveillance systems do not currently provide similar high-fidelity epidemiological metadata to associate with genetic data. As a consequence, it is rarely possible to transform genetic data into actionable knowledge that can be used to genuinely inform risk assessment or prevent outbreaks. Big data approaches are touted as a revolution in decision support, and pose a potentially attractive method for closing the gap between the fidelity of genetic and epidemiological metadata for food safety surveillance. We therefore developed a simple food chain model to investigate the potential benefits of combining 'big' data sources, including both genetic and high-fidelity epidemiological metadata. Our results suggest that, as for any surveillance system, the collected data must be relevant and characterize the important dynamics of a system if we are to properly understand risk: this suggests the need to carefully consider data curation, rather than the more ambitious claims of big data proponents that unstructured and unrelated data sources can be combined to generate consistent insight. Of interest is that the biggest influencers of foodborne infection risk were contamination load and processing temperature, not genotype. This suggests that understanding food chain dynamics would probably more effectively generate insight into foodborne risk than prescribing the hazard in ever more detail in terms of genotype.


Generic Selection Criteria for Safety and Patient Benefit [IV] - Physicochemical and pharmaceutical properties of brand-name and generic ketoprofen tapes.
The physicochemical and pharmaceutical properties (pH, peel force, water-vapor permeability, and stretchability) of brand-name and generic ketoprofen products were evaluated and compared. The pHs of Mohrus as a brand-name product and Teikoku as a generic product were low (about 4). Among the other generic products, Patell and Nichi-Iko had a pH of about 4.3 while Frestol, Raynanon, BMD, and Touchron showed a pH of 4.6-5.2, which was in the pH range of normal healthy skin (4.5-6.5). The adhesive force was high (≥ 1.38) for Mohrus as a brand-name product as well as for Teikoku and Patell as generic products, but it was low (≤ 0.57) for the other 5 generic products. The water-vapor permeabilities of Mohrus as a brand-name product and Teikoku and Patell as generic products were low, being less than 1/6 of those for the other 5 generic products. Among the 5 generic products, BMD showed the highest water-vapor permeability (1,330 g/m²), and the other products also showed a value ≥ 1,100 g/m². The elongatedness of Mohrus was the lowest (15.5 cm), and that of Raynanon was the highest (24.5 cm); the difference was 9 cm. In this study, the physiochemical and pharmaceutical properties of ketoprofen tapes were clarified, which will allow pharmacists to provide products according to the needs of each patient when a brand-name product is changed to a generic one.


Microscopic differential cell counting to identify inflammatory reactions in dairy cow quarter milk samples.
The diagnosis of intramammary infections is mostly based on somatic cell count (SCC) and bacteriological analysis. As an alternative, differential cell counting (DCC) could be a useful method, because it identifies changes in the relative cell populations before the increase in total cell number occurs. The aim of the study was to identify cytological parameters that could be used in the field to classify mammary quarters as healthy or diseased, comparing cyto-bacteriological results with DCC. Overall, 48 cows were randomly selected from 3 herds in Lombardy region of Italy. Herd A was characterized by the absence of contagious microorganisms; in herds B and C, the prevalence of Staphylococcus aureus was 20 and 50%, respectively. Foremilk samples were aseptically collected from 188 quarters and submitted to bacteriological analysis, SCC, and DCC. For statistical analysis, the samples were clustered into 4 health groups, and DCC results were compared in each group. Ninety-six samples were classified as normal secretions (N), 30 as mastitis (M), 15 as latent mastitis (LM), and 47 as unspecific mastitis (UM) based on SCC and bacteriological results. Single percentages of lymphocytes, polymorphonuclear neutrophilic leukocytes (PMNL), or macrophages were first evaluated to established variables capable of identifying healthy and inflamed quarters. Then, combinations of cell populations were tested to increase the discrimination power of DCC: phagocytes, logarithmic PMNL:lymphocyte ratio, and logarithmic phagocyte:lymphocyte ratio. The mean percentage of lymphocytes was significantly higher in group N than in groups LM, UM, and M. The mean percentage of PMNL was significantly lower in group N than in groups UM and M, but not LM. Mean percentages of macrophages were not significantly influenced by the 4 groups. The mean value of phagocytes was significantly lower in group N than in the other groups. Both the logarithmic PMNL:lymphocyte and the logarithmic phagocyte:lymphocyte ratios were significantly lower in group N than in groups LM, UM, and M. Fisher (F-)values were calculated, and the highest F-value was that of log PMNL:lymphocytes ratio (48.23). The explanation for this could be that log PMNL:Lym is the only variable that involved both cell populations statistically influenced by health groups but excluded macrophages. Microscopic DCC has potential as a tool to identify cows affected by any inflammatory process of the mammary gland, with the best results being achieved using log PMNL:lymphocyte as variable.


Flying High-Muscle-Specific Underreplication in Drosophila.
Drosophila underreplicate the DNA of thoracic nuclei, stalling during S phase at a point that is proportional to the total genome size in each species. In polytene tissues, such as the Drosophila salivary glands, all of the nuclei initiate multiple rounds of DNA synthesis and underreplicate. Yet, only half of the nuclei isolated from the thorax stall; the other half do not initiate S phase. Our question was, why half? To address this question, we use flow cytometry to compare underreplication phenotypes between thoracic tissues. When individual thoracic tissues are dissected and the proportion of stalled DNA synthesis is scored in each tissue type, we find that underreplication occurs in the indirect flight muscle, with the majority of underreplicated nuclei in the dorsal longitudinal muscles (DLM). Half of the DNA in the DLM nuclei stall at S phase between the unreplicated G0 and fully replicated G1. The dorsal ventral flight muscle provides the other source of underreplication, and yet, there, the replication stall point is earlier (less DNA replicated), and the endocycle is initiated. The differences in underreplication and ploidy in the indirect flight muscles provide a new tool to study heterochromatin, underreplication and endocycle control.


[Cyanidin as endogenous chelator of metal ions in maize seedling roots].
The property of cyanidin complexation with different metal ions in maize seedlings roots was established using parameters of reflectance spectroscopy and colorimetry. The spectral criteria of pigment association with metals in vivo were evaluated.


Cell surface proteoglycan binds mouse mammary epithelial cells to fibronectin and behaves as a receptor for interstitial matrix.
The proteoglycan (PG) on the surface of NMuMG mouse mammary epithelial cells consists of at least two functional domains, a membrane-intercalated domain which anchors the PG to the plasma membrane, and a trypsin-releasable ectodomain which bears both heparan and chondroitin sulfate chains. The ectodomain binds cells to collagen types I, III, and V, but not IV, and has been proposed to be a matrix receptor. Because heparin binds to the adhesive glycoproteins fibronectin, an interstitial matrix component, and laminin, a basal lamina component, we asked whether the cell surface PG also binds these molecules. Cells harvested with either trypsin or EDTA bound to fibronectin; binding of trypsin-released cells was inhibited by the peptide GRGDS but not by heparin, whereas binding of EDTA-released cells was inhibited only by a combination of GRDS and heparin, suggesting two distinct cell binding mechanisms. In the presence of GRGDS, the EDTA-released cells bound to fibronectin via the cell surface PG. Binding via the cell surface PG was to the COOH-terminal heparin binding domain of fibronectin. In contrast with the binding to fibronectin, EDTA-released cells did not bind to laminin under identical assay conditions. Liposomes containing the isolated intact cell surface PG mimic the binding of whole cells. These results indicate that the mammary epithelial cells have at least two distinct cell surface receptors for fibronectin: a trypsin-resistant molecule that binds cells to the sequence RGD and a trypsin-labile, heparan sulfate-rich PG that binds cells to the COOH-terminal heparin binding domain. Because the cell surface PG binds cells to the interstitial collagens (types I, III, and V) and to fibronectin, but not to basal lamina collagen (type IV) or laminin, we conclude that the cell surface PG is a receptor on epithelial cells specific for interstitial matrix components.


Lasting reduction of severe spasticity after ending chronic treatment with intrathecal baclofen.
To investigate whether the dose of intrathecal baclofen necessary for a sufficient reduction of muscle tone and spasms changes during treatment of severe spasticity. A group of 27 patients received intrathecal baclofen for 61 (SD 18) months. Spasticity remained absent or strongly reduced after stopping the intrathecal baclofen infusion in seven patients. The dose of baclofen could be reduced to 40% of that dose which was originally necessary in 10 patients. The dose remained the same or increased slightly in 10 patients. Possible reasons for the continuing reduction of spasticity after terminating long term intrathecal baclofen infusion in some patients could be: lasting morphological changes in spinal cord neurons by second messenger controlled modulation of gene expression, a toxic effect of baclofen on spinal neurons, muscular atrophy, inflammation due to the catheter, or progression of multiple sclerosis. A higher initial daily dose of intrathecal baclofen might lead to a faster, lasting suppression of spasticity and the development of spastic symptoms might even be prevented by pre-emptive treatment with baclofen in patients with newly acquired lesions of the spinal cord.


[Cheese-washer's disease. A current stable form of extrinsic allergic alveolitis in a rural setting].
Inhalation of organic particles (bacteria, fungi or animal proteins) by sensitized subjects is known to induce extrinsic allergic alveolitis (EAA). The most frequent type of EAA and the best known in rural environment is farmer's lung disease. Nevertheless a rarer form is also to be considered in rural environment: cheesewasher's disease. Here we report 4 cases of cheesewasher's disease, who all presented with relevant aspects of the disease: diversity of antigens involved, prophylaxis problems, severity of the disease, rapidity of onset, reversibility and importance of history in the diagnosis. Penicillium casei usually is the responsible antigen, and precipitating antibodies against these moulds, but against other moulds such as Aspergillus, Circinomucor circilloïdes, Fusarium as well, can be detected in the patient's serum. Thus, in a rural environment, a respiratory symptomatology suggestive of EAA should lead to thorough search for antigens and cheesewasher's disease should be considered. Among the many other diagnostic tests, precipitin determinations are cheap and non invasive and can be very useful in the diagnostic approach.


[Ambulatory surgical interventions in patients with proctological diseases].
The results of 629 operations for the most frequent proctological diseases (hemorrhoid, anal scissure, rectal fistula, acute paraproctitis) were analyzed. 134 operations were performed in outpatient clinic, 225--in one-day hospital and 270 (control group)--in coloproctology department. The place of operation did not influence postoperative period and temporary disability time. The mean stay of patient in outpatient department and hospital surgical unit was 3.8 and 324 hours, respectively. Since the second day after operation in specialized department it is possible to perform therapeutic manipulations outpatient in coloproctology room without negative sequences for patient's health. Cost of the ambulatory operation constituted 28.4% of hospital stay for patients with similar interventions. Surgical treatment of the above diseases could be performed in outpatients setfing in more than 50% patients. The bed resources must be used for patients who need long-term and intensive treatment in specialized department.