Protamine-DNA association in mammalian spermatozoa.
We have previously identified two subsets of basic nuclear proteins of mouse sperm: the protamines and a group of less basic proteins and, with the aid of a polyvalent antiserum, we have demonstrated their differential extractibility by NaCl in reducing solution (Rodman et al., J cell sci 53 (1982) 227) [9]. By affinity purification with isolated mouse sperm protamines we have obtained a protamine-specific fraction of that antiserum and a fraction that contains antibodies to the subset of less basic proteins. With those immunochemical probes we have shown the following The antigenic sites recognized by the protamine-specific antibodies are accessible, intranuclearly, only after the DNA has been removed by DNase I. The antibodies and DNA compete for binding sites on the protamines. DNA removal and consequent availability of the antigenic sites of the protamine molecules to the antibodies are possible only after displacement of the less basic proteins and chromatin decondensation have been induced. Immunoreactivity by the less basic proteins takes place without intervention of DNase. Those data indicate that the protamines are DNA-bound but that the less basic proteins are not or, alternatively, their putative DNA-binding sites do not coincide with their immuno-reactive sites. Those data also suggest that a function of the subset of less basic proteins may be to provide a shield for the protamine-DNA complex. The mouse protamine-affinity-bound antibodies are highly cross-reactive with protamines of other mammalian sperm suggesting that, despite considerable molecular diversity among mammalian protamines, the DNA-binding sites are conserved.


Tracking the elusive prion.
Prion diseases are infectious neurodegenerative fatal disorders. There are currently no treatments or cures. Considerable evidence suggests that the infectious agent is an abnormally folded protein that promotes or seeds its normal cellular isoform to fold into the infectious form. However, the precise mechanism and factors involved in this conversion remain unknown. A major stumbling block to further investigation has been the inability to seed the formation of new infectious material in vitro. Now, however, infectious material has been generated in a cell-free system. Although this system uses cell lysate rather than pure proteins, it nevertheless opens the door to the elucidation of targets of intervention and the development of useful diagnostic and therapeutic approaches.


Perceptions of the use of mobile phones to access reproductive health care services in Tamale, Ghana.
Africa has one of the world's highest populations of young people. In addition, Africa has one of the highest proportions of young people facing the worst health challenges. Although previous scholars have reported that young people were using mobile phones to fill in the gaps in accessing reproductive health services, among other health services, there was little comprehensive research on the perception of young people in Tamale, Ghana, on the use of mobile phones to access reproductive health services. This study analyzed the perceptions on mobile phone use to access reproductive health services among young people in Tamale, Ghana. The research used a quantitative method design from a target population of 72,706 young people from selected peri-urban, low-income, middle income and high-income residential areas in Tamale Metropolis, Ghana. The sample size used was 397 young people. Participants were selected using a stratified multistage sampling strategy. Descriptive statistics were used to analyse the data. A total of 86% of the respondents agree that the use of mobile phones helps to overcome cultural challenges that young people in Tamale encounter in accessing reproductive health care. Also, 84.6% of the respondents agree that the use of mobile phones helps them to overcome inadequate access to reproductive health information and services. The use of mobile phones helps to overcome the negative attitude of health providers toward young people in need of reproductive health services was agreed by most of the respondents [strongly agree (35.4%) and agree (49.4%)]. This study informed highly positive perceptions and attitudes toward the use of mobile phones to access Reproductive Health Services in Tamale, Ghana. There is, therefore the need for the health sector to reform its mode of prescriptions of medication, consultation, and service delivery to leverage on the advantages that mHealth presents.


Intrauterine transmission of COVID-19 in Pregnancy: case report and review of literature.
We report the first case of SARS-CoV-2 pregnancy in the U.S. Our literature review highlights the rarity of COVID-19 intrauterine transmission and the need for clinicians to promptly test neonates born to SARS-CoV-2 positive mothers at delivery for COVID-19. It is imperative to establish the real risk of intrauterine transmission and to develop appropriate preventive and treatment strategies.


Lymphocyte subpopulations transformation studies in an experimental model of intestinal and hepatic amoebiasis.
The lymphocyte subpopulations in peripheral blood and blast transformation were studied on days 0, 3, 7, 11, 15, 20 and 35 after infection in progesterone-treated guinea-pigs which had been experimentally infected with Entamoeba histolytica by intracaecal inoculation. In animals with intestinal infection, lowered T cell numbers and blast transformation were seen during the acute phase with a subsequent tendency to recover. In guinea-pigs with hepatic amoebiasis, both these parameters were significantly depressed throughout the period of study with no tendency to recovery. In progesterone-treated and sham-operated animals, a less marked depression of T cells, was observed. The B cell population did not vary greatly in either group. This study has thus shown that in hepatic amoebiasis there is highly significant depression in both number and function of T cells in comparison to intestinal amoebiasis.


Total healthcare budget: assigning priority and level of asset allocation to the diagnosis and management of urologic diseases.
During the past decade increasing concern has developed as to how money should best be allocated in the healthcare sector and to the different disciplines within health care. In the Western world, healthcare budgets increase dramatically each year, even during periods of economic recession. There are many reasons explaining this evolution, but publicly funded healthcare systems, as in the United Kingdom, appear to control their growth more effectively than the private systems as, for instance, in the United States. The bulk of the increase in healthcare expenditure happens to be attributed to elderly people who are becoming high consumers of healthcare facilities. There are, however, two important ways to tackle the problem: one is based on free market regulation systems, introducing diagnosis related groups and resource based relative value scales, as in the United States. The other starts from evaluating the needs and the demands of the population and, based on these results, tries to build up an appropriate healthcare system, as in The Netherlands. In the realm of urology where most of the workload is concentrated around older patients, one can foresee difficulties concerning budget allocation. New medical treatments are introduced, demanding new management skills of the urologist. This should involve new ways of evaluating the benefits of the interventions. Quality of life measurements seem to be crucial for the future where, for cost-effectiveness reasons, more care than cure could be the new function of the urologist.


Self-rated stress, distress, mental health, and health as modifiers of the association between long-term exposure to ambient pollutants and mortality.
Individual and neighbourhood-scale socioeconomic characteristics modify associations between exposure to air pollution and mortality. The role of stress, which may integrate effects of social and environmental exposures on health, is unknown. We examined whether an individual's perspective on their own well-being, as assessed using self-rated measures of stress and health, modifies the pollutant-mortality relationship. The Canadian Community Health Survey (CCHS)-mortality cohort includes respondents from surveys administered between 2001 and 2012 linked to vital statistics and postal codes from 1981 until 2016. Annual fine particulate matter (PM2.5), nitrogen dioxide (NO2), and ozone (O3) exposure estimates were attached to a sample of cohort members aged 30-89 years (n = 398,300 respondents/3,848,400 person-years). We examined whether self-rated stress, distress, mental health, and general health modified associations between long-term exposure to each pollutant (three-year moving average with one-year lag) and non-accidental mortality using Cox survival models, adjusted for individual- (i.e. socioeconomic and behavioural) and neighbourhood-scale covariates. In fully-adjusted models, the relationship between exposure to pollutants and mortality was stronger among those with poor self-rated mental health, including a significant difference for NO2 (hazard ratio (HR) = 1.15, 95% CI 1.06-1.25 per IQR) compared to those with very good/excellent mental health (HR = 1.05, 95% CI 1.01-1.08; Cochran's Q = 4.01; p < 0.05). Poor self-rated health was similarly associated with higher pollutant-associated HRs, but only in unadjusted models. Stress and distress did not modify pollutant-mortality associations. Poor self-rated mental and general health were associated with increased mortality attributed to exposure to ambient pollutants.


Publisher Correction: Protecting the population with immune individuals.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.


Right hemicolectomy for mesenteric phlebosclerosis potentially caused by long-term use of herbal medicine: A case report and literature review.
Mesenteric phlebosclerosis is a rare ischemic disease affecting the colon. Systemic disease and herbal medicine have been pointed out as possible causes, and the disease is characterized by calcifications involved the mesocolic veins. Patients who do not respond to conservative therapy require surgical treatment. In surgical intervention, an adequate extent of colonic resection is important. We present a case of an 87-year-old woman with mesenteric phlebosclerosis who had consumed herbal medicine for 40 years. She suffered from ileus caused by mesenteric phlebosclerosis, and the symptoms did not improve with conservative therapy. Right hemicolectomy was performed since the disease was localized in the right colon. Long-term use of herbal medicine was considered the potential cause of mesenteric phlebosclerosis. The postoperative course was mostly uneventful. The patient stopped using herbal medicine and had no signs of recurrence 2 years after surgery. The greatest concern in surgery for mesenteric phleboscrerosis is to detect the affected area, which should be removed. Characteristic findings in computed tomography and intraoperative findings can help to determine the optimal extent of colonic resection. Mesenteric phlebosclerosis caused by herbal medicines occurs as localized disease in the right colon compared with mesenteric phlebosclerosis caused by other pathogenesis. Limited colonic resection is usually indicated for mesenteric phlebosclerosis caused by herbal medicine.


Blood finds its own way: Axillary vein thrombosis with extensive chest-wall collaterals.
Hemodialysis catheters are associated with upper extremity deep vein thrombosis, and chronic venous occlusion leads to the formation of collateral pathways. Knowledge of these pathways aids in accurate interpretation of upper extremity venograms. Arteriovenous fistula is the preferred access for chronic hemodialysis, and long-term use of catheters should be avoided.


Astragaloside IV protects against polymicrobial sepsis through inhibiting inflammatory response and apoptosis of lymphocytes.
Sepsis is a major clinical challenge in modern medicine, representing one of the leading causes of death in developed countries. The syndrome is a consequence of a dysregulated immune response, including early uncontrolled systemic inflammation and prolonged immunosuppression in the late phase. The present study was conducted to investigate the therapeutic effects of astragaloside IV (ASI-IV) on the cecal ligation and puncture (CLP)-induced sepsis in mice. C57BL/6 mice were randomly divided into sham control + vehicle, CLP + vehicle, and CLP + ASI-IV groups. ASI-IV (3 mg/kg) was intravenously injected 1 h after CLP surgery. Survival rate, bacterial clearance, inflammatory mediators, phagocytes emigration, histopathology, and lymphocyte apoptosis were examined. The effects of ASI-IV on peritoneal macrophage activation and its underlying mechanisms were also evaluated. We reported that treatment with ASI-IV significantly improved survival in septic mice. In agreement with this protective effect, the pathologic damage that was typically seen in lung and spleen was ameliorated; the level of bacterial burden was lessened; inflammatory cytokines and chemokines in circulation were profoundly reduced; lymphocyte apoptosis was inhibited. ASI-IV suppressed LPS-induced macrophage activation through inhibiting NF-κB and ERK1/2 signaling pathways. ASI-IV protected mice against polymicrobial sepsis by inhibiting inflammatory response and lymphocyte apoptosis. Therefore, ASI-IV might provide a novel therapeutic approach for septic patients.


Marjolin Ulcer: A Comprehensive Review.
To provide a comprehensive review of Marjolin ulcer (MU) to assist clinicians in understanding the epidemiology, etiology, pathogenesis, diagnosis, and treatment of MU. This continuing education activity is intended for physicians, physician assistants, nurse practitioners, and nurses with an interest in skin and wound care. After participating in this educational activity, the participant will:1. Describe the epidemiology, pathogenesis, and clinical manifestations of MU.2. Summarize the diagnostic and treatment approaches for patients who have an MU. This article aims to provide a comprehensive review of Marjolin ulcer (MU) to assist clinicians in understanding the epidemiology, etiology, pathogenesis, diagnosis, and treatment of MU. Marjolin ulcer presents with clear signs and symptoms of malignant degeneration in chronic wounds. It can be prevented by raising awareness and educating wound care providers appropriately about its signs and symptoms.


[Sleep disorders in chronic renal failure].
Sleep disorders are common in patients with chronic renal failure (CRF), especially in those receiving hemodialysis. Sleep-related complaints in this patient population may include insomnia, daytime sleepiness or fatigue and depression. In addition to causing impairment of daytime function and quality of life, sleep apnea may also increase the cardiovascular morbidity and mortality, especially in dialysis patients. In CRF patients, an increased prevalence of sleep apnea, restless legs syndrome and periodic limb movement during sleep has been reported. Epidemiology, pathophysiology and treatment of sleep disorders in CRF and dialysis patients are still unclear and require further research.


Gelatin embedding and LED autofluorescence reduction for rodent spinal cord histology.
We present two innovations in histological technique for rodent spinal cord: gelatin embedding and LED photobleaching. Gelatin embedding uses liquid gelatin solution to permeate delicate biological structures then solidify to provide mechanical support throughout dissection, vibratome sectioning, and staining. LED photobleaching uses high-intensity visible light during blocking and primary incubations to reduce autofluorescence in tissue sections before fluorescent secondaries are added. We found gelatin embedding improved mechanical stability without interfering with immunohistochemical staining. Gelatin embedding also preserved some spinal roots and provided an opportunity for dye-less and cut-less tracking of left/right orientation during free-floating staining, which is valuable for tissue samples that have no spare areas that can be marked. LED photobleaching greatly reduced autofluorescence and added essentially no extra time or labor to the process. Descriptions of the techniques and characterization data are provided.


Parallel speciation in Astyanax cave fish (Teleostei) in Northern Mexico.
We investigated differentiation processes in the Neotropical fish Astyanax that represents a model system for examining adaptation to caves, including regressive evolution. In particular, we analyzed microsatellite and mitochondrial data of seven cave and seven surface populations from Mexico to test whether the evolution of the cave fish represents a case of parallel evolution. Our data revealed that Astyanax invaded northern Mexico across the Trans-Mexican Volcanic Belt at least three times and that populations of all three invasions adapted to subterranean habitats. Significant differentiation was found between the cave and surface populations. We did not observe gene flow between the strongly eye and pigment reduced old cave populations (Sabinos, Tinaja, Pachon) and the surface fish, even when syntopically occurring like in Yerbaniz cave. Little gene flow, if any, was found between cave populations, which are variable in eye and pigmentation (Micos, Chica, Caballo Moro caves), and surface fish. This suggests that the variability is due to their more recent origin rather than to hybridization. Finally, admixture of the young Chica cave fish population with nuclear markers from older cave fish demonstrates that gene flow between populations that independently colonized caves occurs. Thus, all criteria of parallel speciation are fulfilled. Moreover, the microsatellite data provide evidence that two co-occurring groups with small sunken eyes and externally visible eyes, respectively, differentiated within the partly lightened Caballo Moro karst window cave and might represent an example for incipient sympatric speciation.


Closed-loop control if the inspired fraction of oxygen in mechanical ventilation.
Supplemental oxygen treatment of patients on mechanical ventilation is crucial in maintaining the patients' oxygen levels in the normal range. The purpose of this study was to evaluate the effectiveness of a closed-loop controller for automatic adjustment of the fraction of inspired oxygen, FIO2. More specifically, the aim of the study was to assess the robustness of the controller in correcting hypoxemia as well as its effectiveness in prevention of hyperoxemia and oxygen toxicity. The microprocessor-based feedback control system combines a rapid control algorithm with a proportional-integral-derivative (PID) control procedure to automatically adjust FIO2. The system is designed to prevent hypoxemia by applying a stepwise control procedure in response to rapid declines in arterial oxygen saturation while fine-tuning FIO2 and avoiding hyperoxemia by resuming to the PID control procedure when appropriate. The system includes a sophisticated safeguard unit which is designed to communicate any oxygenation problems or measurement artifacts to the medical personnel while keeping FIO2 at a safe and sufficiently high level. The control system has been tested by using computer simulations as well as animal studies. In response to different disturbances, the arterial oxygen saturation returned to the normal safe range within less than 20 seconds, thereby avoiding any untoward effects of hypoxemia. Under steady state conditions, the variations in arterial oxygen saturation were kept within +/- 3% of the mean value. The controller corrected hypoxemia within seconds while preventing hyperoxemia, rejecting artifacts, and minimizing exposure to high concentrations of oxygen. The results of the study attest to the reliability of the proposed closed-loop control scheme for automatic adjustment of FIO2. Further evaluation of the controller will require testing the effectiveness of the system on different patient groups.


A simple model of the electrosensory electromotor loop in Gymnotus omarorum.
This article introduces and tests a simple model that describes a neural network found in nature, the electrosensory control of an electromotor pacemaker. The cornerstone of the model is an early-stage filter based on the subtraction of a feedforward integrated version of the recent sensory past from the present input signal. The output of this filter governs the modulation of a premotor pacemaker command driving the sensory signal carrier generation and, in consequence, the timing of subsequent electrosensory input. This early filter has a biological parallel in the known connectivity of the first electrosensory relay within the brain stem of the weakly electric fish Gymnotus omarorum. Our biomimetic model of this active, perception-driven action-sensation cycle was contrasted with previously published and here provided new data. When the amplitude of the electrosensory input was manipulated to mimic previous experiments on the novelty detection characteristics, the model reproduces them rather faithfully. In addition, when we applied continuous variations to the input it shows that increases in stimulus amplitudes are followed by increases in the EOD rate, but decreases do not cause rate modulation suggesting a rectification in some stage of the loop. These behavioral experiments confirmed results generated the simulations suggesting that beyond explaining the novelty detection process this simple model is a good description of the electrosensory -electromotor loop in pulse weakly electric fish.


Characterization of the influence of unsaturated free fatty acids on brain GABA/benzodiazepine receptor binding in vitro.
We have investigated the effect of unsaturated free fatty acids (FFAs) on the brain GABA/benzodiazepine receptor chloride channel complex from mammalian, avian, amphibian, and fish species in vitro. Unsaturated FFAs with a carbon chain length between 16 and 22 carbon atoms enhanced [3H]diazepam binding in rat brain membrane preparations, whereas the saturated analogues had no effect. The enhancement of [3H]diazepam binding by oleic acid was independent of the incubation temperature (0-30 degrees C) of the binding assay and not additive to the enhancement by high concentrations of Cl-. In rat brain preparations, the stimulation of [3H]diazepam binding by oleic acid (10(-4) M) was independent of the ontogenetic development. Phylogenetically, large differences were found in the effect of unsaturated FFAs on [3H]diazepam and [3H]muscimol binding: In mammals and amphibians, unsaturated FFAs enhanced both [3H]-muscimol and [3H]diazepam binding to 150-250% of control binding. In 17 fish species studied, oleic acid (10(-4) M) stimulation of [3H]diazepam binding was weak (11 species), absent (four species), or reversed to inhibition (two species), whereas stimulation of [3H]muscimol binding was of the same magnitude as in mammals and amphibians. In 10 bird species studied, only weak enhancement of [3H]muscimol binding (110-130% of control) by oleic acid (10(-4) M) was found, whereas [3H]diazepam binding enhancement was similar to values in mammal species. Radiation inactivation of the receptor complex in situ from frozen rat cortex showed that the functional target size for oleic acid to stimulate [3H]flunitrazepam binding has a molecular mass of approximately 200,000 daltons.(ABSTRACT TRUNCATED AT 250 WORDS)


TGA/Chemometrics addressing innovative preparation strategies for functionalized carbon nanotubes.
In this work, functionalized carbon nanotubes (CNTs) using two polyamine polymers, polyethyleneimine (PEI) and polyamidoamine dendrimer (PAMAM), were investigated by thermal analysis in order to address preparation strategies to obtain low cytotoxic compounds with the ability to conjugate microRNAs and, at the same time, to transfect efficiently endothelial cells. Thermogravimetric analysis (TGA) was coupled to chemometrics as a novel analytical strategy to characterize functionalized CNTs from different preparation conditions. In particular, two starting materials were considered: very small CNTs and carboxylated CNTs (CNT-COOH) in order to examine the affinity with polymers. Chemometrics permitted to compare results from TGA and to investigate the effect of a number of factors affecting the synthesis of coated nanotubes including a different amount of involved polymer and the time required for the suspension for a satisfactory and reproducible preparation procedure. The results demonstrated the effectiveness of TGA as a tool able to address synthesis of coated CNTs to be employed as efficient drug delivery vectors in biomedical applications.


Mutations at position 1122 in the catalytic domain of the mouse ras-specific guanine nucleotide exchange factor CDC25Mm originate both loss-of-function and gain-of-function proteins.
The role of two residues within the catalytic domain of CDC25Mm, a mouse ras-specific guanine nucleotide exchange factor (GEF), was investigated by site-directed mutagenesis. The function of the mutant proteins was tested in vivo in both a Saccharomyces cerevisiae cdc25 complementation assay and in a mammalian fos-luciferase assay, and in in vitro assays on human and yeast Ras proteins. Mutants CDC25Mm(E1048K) and CDC25Mm(S1122V) were shown to be (partly) inactive proteins, similar to their yeast homologs. Mutant CDC25Mm(S1122A) showed higher nucleotide exchange activity than the wild type protein on the basis of both in vitro and in vivo assays. Thus, alanine and valine substitutions at position 1122 within the GEF catalytic domain originate mutations with opposite biological properties, indicating an important role for position 1122 in GEF function.


The Double Burden of Undernutrition and Overnutrition in Developing Countries: an Update.
Many developing countries have achieved a remarkable improvement in nutrition status in the past decades. However, the prevalence of undernutrition remains a serious problem. At the same time, the prevalence of obesity is increasing substantially, and in some countries, it has approached that of developed countries. This article provides an update on this double burden of malnutrition (DBMN) in developing nations. One hundred countries (lower, middle-lower, and upper-middle income countries) were selected and analysed, and to support the analysis, a systematic review of current published studies was performed. The results show that DBMN already exists in almost all developing countries and that the DBMN ratio (i.e., overweight/underweight) has increased as income per capita has increased. DBMN may manifest within the community, household, or individual. In addition to common factors, poor nutrition in early childhood is suggested as another important driving factor behind the rising obesity rate in most developing countries. A life-course approach has been proposed to prevent undernutrition and overnutrition and should be integrated into the development of health systems to control double burden in developing countries.


Effect of ovarian stimulation by different gonadotrophin treatments on in vivo and in vitro reproductive efficiency of rabbit does under high ambient temperature.
Non-lactating multiparous NZW rabbit does (n = 227) were used in two experiments. In the 1st experiment (n = 87), does were i.m. injected with 0.1-ml saline/doe in day 0 (control, n = 29). Other does were injected with 25 IU equine chorionic gonadotrophin (eCG), followed by 0.2-ml gonadotrophin-releasing hormone (GnRH, n = 29) or 75 IU human chorionic gonadotrophin (hCG, n = 29) per doe 48 h later. After 60 h of day 0, does in all groups were artificially inseminated (AI). In the 2nd experiment, does (n = 140) were mated (AI) after synchronization of estrus/ovulation with 25 IU eCG, and 75 IU hCG 48 h later. On day 5 post-AI, does were injected with saline (control), 75 IU hCG, 0.2 ml GnRH, or 25 IU eCG per doe. Injection of eCG with GnRH or hCG pre-AI significantly increased corpora lutea number, ovulation rate, total number/doe and recovery rate of embryos, viable embryos, hatched blastocysts, in vivo reproductive parameters, and concentration of progesterone and progesterone/estradiol 17-β ratio. Injection of eCG on day 5 post-AI significantly improved large and total follicle number, and in vivo reproductive efficiency. The corpora lutea number and impantation sites were significantly increased in the hCG and eCG groups. Fetal loss rate significantly increased only in the GnRH group. Under high ambient temperature, administration of eCG with hCG or GnRH injection pre-AI could be synchronized estrus/ovulation for improving in vivo and in vitro embryo production. In addition, pregnancy outcomes could be enhanced in rabbit does induced to ovulation by a single eCG or hCG dose on day 5 post-AI.


Incidence of adamantane resistance among influenza A (H3N2) viruses isolated worldwide from 1994 to 2005: a cause for concern.
Adamantanes have been used to treat influenza A virus infections for many years. Studies have shown a low incidence of resistance to these drugs among circulating influenza viruses; however, their use is rising worldwide and drug resistance has been reported among influenza A (H5N1) viruses isolated from poultry and human beings in Asia. We sought to assess adamantane resistance among influenza A viruses isolated during the past decade from countries participating in WHO's global influenza surveillance network. We analysed data for influenza field isolates that were obtained worldwide and submitted to the WHO Collaborating Center for Influenza at the US Centers for Disease Control and Prevention between Oct 1, 1994, and Mar 31, 2005. We used pyrosequencing, confirmatory sequence analysis, and phenotypic testing to detect drug resistance among circulating influenza A H3N2 (n=6524), H1N1 (n=589), and H1N2 (n=83) viruses. More than 7000 influenza A field isolates were screened for specific aminoacid substitutions in the M2 gene known to confer drug resistance. During the decade of surveillance a significant increase in drug resistance was noted, from 0.4% in 1994-1995 to 12.3% in 2003-2004. This increase in the proportion of resistant viruses was weighted heavily by those obtained from Asia with 61% of resistant viruses isolated since 2003 being from people in Asia. Our data raise concerns about the appropriate use of adamantanes and draw attention to the importance of tracking the emergence and spread of drug-resistant influenza A viruses.


Mn(2+)-doped silica nanoparticles for hepatocyte-targeted detection of liver cancer in T1-weighted MRI.
With an aim to examine the possibility of developing a liver-specific MRI contrast agent that takes advantages of brightly enhanced MR images by Mn²⁺ whilst making up the limitations of the pre-developed contrast agent, the Mn²⁺-doped SiO₂ nanoparticles (Mn-SiO₂) were synthesized and their characteristics as MR contrast agents were investigated. The in vitro and in vivo investigations showed that Mn-SiO₂ has unique MR contrast-enhancing characteristics that activate positive contrast enhancement in T1-weighted MR images only under low pH conditions by liberating Mn²⁺ ions from MR inactive nanoparticles. The administration of Mn-SiO₂ to an orthotopic xenograft model of human hepatocellular carcinoma (HCC) resulted in a differentiation of enhancement periods between HCC and normal parenchyma tissues on T1-weighted MR images and consequently presented the duplicates of the highly contrast-enhanced liver image with an equal liver-to-HCC contrast ratio but opposite contrast. The Mn-SiO₂-enhanced MR imaging therefore allowed for the repetitive detection of the HCC within a single MR imaging session, which can help us to achieve more reliable diagnosis and characterization of liver lesions than is possible with any currently used Mn²⁺-based contrast agent. In addition, the in vivo biodistribution study also supported the effectiveness of Mn-SiO₂ nanoparticles as a liver-specific MRI contrast agent, which efficiently delivers and releases the T1-contrasting Mn²⁺ ions to targeted hepatocytes.


Allergic conjunctivitis and uveitis models: reappraisal with some marketed drugs.
The purpose of this study was to assess the activity of some marketed products in ocular non-immune and immune type I hypersensitivity reactions, and during intra-ocular type III hypersensitivity. In order to compare these activities, we improved and validated three different models of ocular allergic reaction already known for their ability to reproduce allergic conjunctivitis or uveitis. Allergic conjunctivitis was induced by ocular immediate hypersensitivity after instillation of compound 48/80 in the rat, or an active anaphylaxis reaction with ovalbumin immunisation and challenge in the guinea pig. Uveitis was induced by a reverse passive anaphylaxis reaction using intra-vitreal rabbit anti-bovine IgG anti-serum sensitisation and intravenous bovine gamma-globulin challenge in the rabbit. Clinical scores and blood-tissue permeability indices were studied. Using the same schedule of ocular instillation, the effects of Livostin (levocabastine 0.05%), Almide (lodoxamide 0.1%), Opticrom (sodium cromoglycate 2%), Ocufen (flurbiprofen 0.03%), Acular (ketorolac 0.5%) and 0.3% chlorpheniramine maleate were compared to positive and negative controls. We demonstrated the potent activity of chlorpheniramine maleate 0.3% and Livostin in both allergic conjunctivitis models. Significant activity was also evidenced with Almide, which was only active in the non-immune allergy model, while Opticrom was definitely not active in these models. In the uveitis model, Acular and Ocufen are active and potent drugs, while Livostin and Almide were not active. These results are discussed with respect to the models used and the mediators involved.


Shape from shading: estimation of reflectance map.
The reflectance map used by the visual system for perception of shape from shading was estimated. In Experiment 1, an image of a cylinder or a sphere illuminated from the viewer's direction was presented, and subjects estimated the cross-section of perceived 3D-shape. The reflectance map was estimated from the relationship between the stimulus image intensities and the slants of the measured cross-section. The estimated reflectance maps were not the ones based on Lambertian reflectance properties. In Experiment 2, whether perceived shapes could be predicted based on the reflectance maps obtained in Experiment 1 was examined. Subjects performed the same shape estimation task with images of cylinders generated by the reflectance map obtained in Experiment 1. The perceived shapes coincided well with the shapes used for stimulus image generation. These results indicate that the visual system's estimation of shape from shading can be fully understood based on empirically obtained reflectance maps without mentioning its inaccurate nature which has been claimed by past studies.


Toll-like receptor 4: a potential link between "danger signals," the innate immune system, and preeclampsia?
Toll-like receptors (TLRs) recognize microbial ligands and host products that are released during tissue damage, the so-called "danger signals." This study was conducted to determine whether changes in TLR-4 and TLR-2 expressions can be detected in the trophoblasts at the placental bed of women with and without preeclampsia. Placental bed biopsy specimens were obtained from women with: (1) normal term pregnancies with and without labor (each n = 20); (2) preeclampsia who delivered preterm (n = 15); and (3) preterm labor and intact membranes with and without chorioamnionitis (each n = 15). The expression pattern of TLR-4 and TLR-2 in the trophoblasts was analyzed by double immunohistochemistry. (1) The median percentage of TLR-4 positive interstitial trophoblasts was significantly higher in patients with preeclampsia than in patients with preterm labor without or with histologic chorioamnionitis (P = .0002 and P = .02, respectively). (2) The median percentage of TLR-2 positive interstitial trophoblasts was not different among the study groups (P>.05). (3) TLR-4 positive trophoblasts were also frequently immunoreactive to activated nuclear factor-kappaB, tumor necrosis factor-alpha, and M30 (a specific apoptosis antigen for trophoblast). (4) Lipopolysaccharide treatment inhibited the migration of trophoblast cell lines in vitro. TLR-4 protein expression is increased in interstitial trophoblasts of patients with preeclampsia. We propose that "danger signals" at the feto-maternal interface, which are recognized by trophoblasts through TLR-4, may play a key role in the creation of a local abnormal cytokine milieu. This suggests a novel mechanism that links the activation of the innate immune system through TLR-4 and preeclampsia.


Large intragenic deletion of CDC73 (exons 4-10) in a three-generation hyperparathyroidism-jaw tumor (HPT-JT) syndrome family.
Inactivating mutations of CDC73 cause Hyperparathyroidism-Jaw Tumour syndrome (HPT-JT), Familial Isolated Hyperparathyroidism (FIHP) and sporadic parathyroid carcinoma. We conducted CDC73 mutation analysis in an HPT-JT family and confirm carrier status of the proband's daughter. The proband had primary hyperparathyroidism (parathyroid carcinoma) and uterine leiomyomata. Her father and daughter had hyperparathyroidism (parathyroid adenoma) but no other manifestations of HPT-JT. CDC73 mutation analysis (sequencing of all 17 exons) and whole-genome copy number variation (CNV) analysis was done on leukocyte DNA of the three affecteds as well as the proband's unaffected sister. A novel deletion of exons 4 to 10 of CDC73 was detected by CNV analysis in the three affecteds. A novel insertion in the 5'UTR (c.-4_-11insG) that co-segregated with the deletion was identified. By in vitro assay the 5'UTR insertion was shown to significantly impair the expression of the parafibromin protein. Screening for the mutated CDC73 confirmed carrier status in the proband's daughter and the biochemistry and ultrasonography led to pre-emptive surgery and resolution of the hyperparathyroidism. A novel gross deletion mutation in CDC73 was identified in a three-generation HPT-JT family emphasizing the importance of including screening for large deletions in the molecular diagnostic protocol.


Chemoprevention with interferon alfa and 13-cis retinoic acid in the adjunctive treatment of head and neck cancer.
Retinoids have been increasingly used since the mid-1960s for the treatment of leukoplakia and dysplasia of the head and neck. Studies of their use in the treatment of carcinomas of the head and neck, usually in combination with interferons, have also been published in recent years. 30 patients (25 men, five women) with UICC stage IV were given adjunctive treatment with a combination of 3 x 3 million IU of interferon alfa SC weekly and 0.5 mg/kg body weight of 13-cis retinoic acid PO daily for a maximum duration of 6 months. The therapeutic benefits and side effects are reported here. Therapy was completed as scheduled in 16 out of 30 patients. Reasons for stopping treatment: progressive disease (ten patients), side effects (four patients). 18 patients were tumor-free following treatment. 16 patients displayed a complete response one year after completion of adjunctive treatment. Retinoic-associated side effects observed included xerostomia (90%), dysphagia (67%), weight loss (50%), flush (50%) and cachexia (7%). Interferon-associated side effects included pyrexia and moderate hematological changes. Adjunctive combination treatment with interferon alfa and 13-cis retinoic acid appears to be beneficial to patients with head and neck cancer. The side effects are moderate.


Near wall Prandtl number effects on velocity gradient invariants and flow topologies in turbulent Rayleigh-Bénard convection.
The statistical behaviours of the invariants of the velocity gradient tensor and flow topologies for Rayleigh-Bénard convection of Newtonian fluids in cubic enclosures have been analysed using Direct Numerical Simulations (DNS) for a range of different values of Rayleigh (i.e. [Formula: see text]) and Prandtl (i.e. [Formula: see text] and 320) numbers. The behaviours of second and third invariants of the velocity gradient tensor suggest that the bulk region of the flow at the core of the domain is vorticity-dominated whereas the regions in the vicinity of cold and hot walls, in particular in the boundary layers, are found to be strain rate-dominated and this behaviour has been found to be independent of the choice of Ra and Pr values within the range considered here. Accordingly, it has been found that the focal topologies S1 and S4 remain predominant in the bulk region of the flow and the volume fraction of nodal topologies increases in the vicinity of the active hot and cold walls for all cases considered here. However, remarkable differences in the behaviours of the joint probability density functions (PDFs) between second and third invariants of the velocity gradient tensor (i.e. Q and R) have been found in response to the variations of Pr. The classical teardrop shape of the joint PDF between Q and R has been observed away from active walls for all values of Pr, but this behavior changes close to the heated and cooled walls for high values of Pr (e.g. [Formula: see text]) where the joint PDF exhibits a shape mirrored at the vertical Q-axis. It has been demonstrated that the junctions at the edges of convection cells are responsible for this behaviour for [Formula: see text], which also increases the probability of finding S3 topologies with large negative magnitudes of Q and R. By contrast, this behaviour is not observed in the [Formula: see text] case and these differences between flow topology distributions in Rayleigh-Bénard convection in response to Pr suggest that the modelling strategy for turbulent natural convection of gaseous fluids may not be equally well suited for simulations of turbulent natural convection of liquids with high values of Pr.


A comparative evaluation of the quality of cryoprecipitate prepared from 350 ml versus 450 ml of whole blood and different methods of thawing of plasma: A prospective observational study.
Cryoprecipitate is used in conditions like hypofibrinogenemia, massive transfusion with bleeding, and factor XIII deficiency. The current guidelines support the preparation of cryoprecipitate from 450 ml whole blood. But 350 ml of whole blood collection is expected from low body weight (<55 kg) donors. However, no standardized criteria exist for preparing cryoprecipitate from 350 ml of whole blood. This study compared the fibrinogen and factor VIII levels in cryoprecipitate units prepared from 350 ml versus 450 ml whole blood collection. The study also compared the fibrinogen and factor VIII levels prepared by circulating water bath versus blood bank refrigerator (BBR) thawing method. A total of 128 blood bags were equally divided into groups A and B for 450 and 350 ml whole blood collection further subdivided into subgroups based on thawing methods. The fibrinogen and factor VIII yield were analyzed in the cryoprecipitates prepared from both groups. The factor VIII levels were significantly higher in cryoprecipitate made from 450 ml whole blood collection (P = 0.02). The BBR method of plasma thawing resulted in better fibrinogen recovery than the cryo bath method. Whereas vice versa in the case of factor VIII recovery. A weak but significant positive correlation was noted in factor VIII levels with the plasma volume. Over 75% of the cryoprecipitates prepared from 350 ml whole blood passed the fibrinogen and factor VIII quality control criteria. So, 350 ml whole blood collection from low body weight (<55 kg) donors could be utilized to prepare cryoprcipitates. However, future clinical studies should focus on the cryoprecipitate's clinical efficacy prepared from 350 ml of whole blood.


Molecular genetics of cytoplasmic male sterility and restorer-of-fertility for the fine tuning of pollen production in crops.
Cytoplasmic male sterility (CMS) is an increasingly important issue within the context of hybrid seed production. Its genetic framework is simple: S-cytoplasm for male sterility induction and dominant allele of the restorer-of-fertility gene (Rf) for suppression of S. However, breeders sometimes encounter a phenotype of CMS plants too complex to be explained via this simple model. The molecular basis of CMS provides clue to the mechanisms that underlie the expression of CMS. Mitochondria have been associated with S, and several unique ORFs to S-mitochondria are thought to be responsible for the induction of male sterility in various crops. Their functions are still the subject of debate, but they have been hypothesized to emit elements that trigger sterility. Rf suppresses the action of S by various mechanisms. Some Rfs, including those that encode the pentatricopeptide repeat (PPR) protein and other proteins, are now considered members of unique gene families that are specific to certain lineages. Additionally, they are thought to be complex loci in which several genes in a haplotype simultaneously counteract an S-cytoplasm and differences in the suite of genes in a haplotype can lead to multiple allelism including strong and weak Rf at phenotypic level. The stability of CMS is influenced by factors such as the environment, cytoplasm, and genetic background; the interaction of these factors is also important. In contrast, unstable CMS becomes inducible CMS if its expression can be controlled. CMS becomes environmentally sensitive in a genotype-dependent manner, suggesting the feasibility of controlling the expression of CMS.


Influence of the polymorphism of the DUSP14 gene on the expression of immune-related genes and development of pulmonary tuberculosis.
Recently, a genome-wide screening identified a functional single-nucleotide polymorphism in dual-specificity phosphatase 14 gene (DUSP14), which was associated with pulmonary tuberculosis (TB) in a West African study. DUSP14 regulates T-cell proliferation and cytokine production in a negative way via dephosphorylation and inactivation of key signaling molecules. The aim of this study is to further explore the possible significance of the DUSP14 polymorphism. Total RNA was extracted from the whole blood of 109 healthcare workers (HCWs) in Vietnam and subjected to quantitative reverse-transcription PCR for DUSP14 and 20 immune-related genes. DUSP14 rs1051838 was genotyped in 502 new pulmonary TB patients and 506 healthy controls. Among disease-free individuals (HCWs), T-helper type-1 (Th1)-related genes, interferon-gamma receptor 2 (IFNGR2) and signal transducer and activator of transcription-1 (STAT1) mRNA levels significantly increased as the number of A alleles of rs1051838 increased, whereas the DUSP14 mRNA level tended to decrease. The AA genotype was associated with protection against active TB in younger patients (⩽45 years old, OR=0.63, 95% CI 0.44-0.90). Our results suggest that a low-expression genotype of DUSP14 accompanied by high transcript levels of Th1 immune-related genes may confer protection against early TB development.


Comparative Efficacy of Cardiac Resynchronization Therapy in Africans Americans Compared With European Americans.
Race has seldomly been reported in the major clinical trials of cardiac resynchronization therapy (CRT). When described, African Americans (AAs) were substantially under-represented. This study sought to compare reverse ventricular remodeling and long-term outcomes in AAs versus European Americans (EAs) with advanced heart failure who underwent CRT. We extracted demographic (including race), clinical, and echocardiographic data on patients with advanced heart failure who underwent CRT with a left ventricular ejection fraction (LVEF) ≤35% and a QRS duration ≥120 ms. Long-term outcomes were compared between AAs and EAs. In patients in whom follow-up echocardiograms were available, improvement in LVEF (defined as an absolute improvement ≥5%) was compared between races. From a cohort of 662 patients, there were 88 AAs and 574 EAs. At a mean follow-up of 5.0 ± 2.5 years, survival rate free of left ventricular assist device (LVAD) and heart transplant was 54.5% for AAs and 53.8% for EAs (log-rank p = 0.997). In multivariate analysis, there was no difference in survival free of heart transplant or LVAD based on race (hazard ratio 1.1 [0.74 to 1.56], p = 0.72, EAs race as referent); 424 patients had a follow-up echocardiogram (55.4% EAs and 64.7% AAs). In multivariate analysis, there was no difference in the incidence of response based on race (1.1 [0.6 to 2.1, p = 0.80], EAs as referent). AAs derive similar benefits with CRT compared with EAs in terms of improvement in LVEF and long-term survival free of LVAD and heart transplant.


Relationship between computerized wheeze detection and lung function parameters in young infants.
Computerized respiratory sound analysis (CORSA) has been validated in the assessment of wheeze in infants, but it is unknown whether automatically detected wheeze is associated with impaired lung function. This study investigated the relationship between wheeze detection and conventional lung function testing (LFT) parameters. CORSA was performed using the PulmoTrack® monitor in 110 infants, of median (interquartile range) postmenstrual age 50 (46-56) weeks and median body weight 4,810 (3,980-5,900) g, recovering from neonatal intensive care. In the same session, LFT was performed, including tidal breathing measurements, occlusion tests, body plethysmography, forced expiratory flow by rapid thoracoabdominal compression, sulfur hexafluoride (SF6 ) multiple breath washout (MBW), and capillary blood gas analysis. Infants were classified as wheezers or non-wheezers using predefined cut-off values for the duration of inspiratory and expiratory wheeze. Wheezing was detected in 72 (65%) infants, with 43 (39%) having inspiratory and 53 (48%) having expiratory wheezing. Endotracheal mechanical ventilation in the neonatal period for > 24 hr was associated with inspiratory wheeze (P = 0.009). Airway resistance was increased in both inspiratory (P = 0.02) and expiratory (P = 0.004) wheezers and correlated with the duration of expiratory wheeze (r = 0.394, P < 0.001). Expiratory wheezers showed a significant increase in respiratory resistance (P = 0.001), time constant (0.012), and functional residual capacity using SF6 MBW (P = 0.019). There was no association between wheezing and forced expiratory flow or blood gases. CORSA can help identify neonates and young infants with subclinical airway obstruction and may prove useful in the follow-up of high-risk infants.


Implant placement under existing removable dental prostheses and its effect on masticatory performance.
The aim of this within-subject study was to evaluate the outcome with implant-tooth-supported removable partial dental prostheses (RPDP group) and implant-supported removable complete dental prostheses (edentulous group) in terms of masticatory performance and self-assessment. Thirty patients participated in this prospective clinical study (RPDP group: n = 12; edentulous group: n = 18). The prostheses were supported in strategically advantageous regions by placing implants with ball attachments and corresponding matrices in the existing dentures. The masticatory performance was evaluated with the Swallowing Threshold Test Index (STTI), the number of chewing strokes, and the time needed until swallowing at pre-treatment and 6 weeks after integration of ball attachments. Additionally, patients scored chewing satisfaction before and after implantation on a visual analogue scale. The STTI increased significantly (p ≤ 0.05) after implant therapy in the edentulous group but not in the RPDP group. Furthermore, the STTI was significantly higher (p ≤ 0.05) in the RPDP group than in the edentulous group at pre-treatment, however, not after therapy (P > 0.05). All patients were very satisfied after therapy concerning ability of speaking, chewing, and stability of their prosthesis. Patients of the edentulous group benefit more from strategically placed implants under the existing dentures than patients from the RPDP group. However, according to the subjective assessment, the chewing satisfaction generally increased for both groups after implant therapy. Patients with a strongly reduced dentition and edentulous patients benefit from strategically placed implants under the existing removable dentures.


One-stage revision anterior cruciate ligament reconstruction in cases with excessive tunnel osteolysis. Results of a new technique using impaction bone grafting.
This level IV study describes a new one-stage procedure for revision ACL reconstruction in cases with extreme tunnel widening. Eight consecutively treated subjects requiring ACL revision and presenting with excessive tunnel widening (87.5% to 250% tunnel enlargement) were included in this study. The graft-tunnel mismatch was resolved in this one-stage revision procedure by the use of custom-made eight to 10 mm cylindrical shaped bone allografts in a press-fit construct with the ACL-graft in combination with the usual fixation devices for ACL-reconstruction. All subjects were evaluated pre-operatively and at a minimum follow-up of one year by the IKDC objective and subjective scores, KOOS, and Tegner activity scale. Mean improvement was 24.8 ± 16.1 on the KOOS evaluation (P-value 0,006) and 38.1 ± 16.8 on the IKDC subjective score (P-value 0,001). The objective IKDC scores improved significantly with an average of one grade (P-value 0,038). Anterior laxity as determined on the KT-1000 arthrometer improved with an average of 3.63 mm compared to the situation before primary reconstruction, and the Pivot-shift test was negative in all but one patient after the revision procedure while positive in all patients before primary reconstruction. This new surgical technique using eight to 10 mm allograft bone cylinders for the management of excessive tunnel enlargement at single stage revision ACL reconstruction delivers excellent results after minimum one year of follow-up. The results of this study have the potential to lower the threshold for one-stage surgery in ACL revision complicated by extreme tunnel widening.


Untangling human milk oligosaccharides and infant gut microbiome.
The developing gut microbiome in infancy plays a key role in shaping the host immune system and metabolic state, and human milk is the main factor influencing its composition. Human milk does not only serve to feed the baby, but also to help the new-born adapt to its new environment and microbial exposures. Human milk protects the infant by providing multiple bioactive molecules, including human milk oligosaccharides (HMOs), which are the third most abundant solid component after lipids and lactose. The infant is unable to digest HMOs, so they reach the small and large intestines intact where they have many roles, including acting as prebiotics. Bifidobacterium spp. are the main, but not the only, commensals equipped with genes for HMO degradation. In this review we will outline the HMOs structures and functions, list the genes needed for their digestion, and describe the main strategies adopted by bacteria for their utilization.


Prevention of diisopropylphosphorofluoridate (DFP)-induced skeletal muscle fiber lesions in rat.
The objective of the present investigation was to assess the comparative efficacy of prophylactic treatment with d-tubocurarine (d-TC) (0.075 mg/kg), atropine sulfate (16 mg/kg), and atropine methylnitrate (16 mg/kg), employed singly or in combination against the diisopropylphosphorofluoridate (DFP)-induced myopathy in rat. DFP (1.5 mg/kg, s.c.) produced signs of cholinergic toxicity with predominantly peripheral involvement manifest as severe muscle fasciculations beginning within 5-7 min and persisting in excess of 4-6 h. Maximal muscle fiber necrosis was observed within 24 h. Rats were protected against the apparent behavioural and morphological changes as well as electrophysiological signs of neuromuscular toxicity by all pretreatment agents. Combined pretreatment with d-TC (0.075 mg/kg, s.c.) and atropine methylnitrate (16 mg/kg, s.c.) was found to be most effective in attenuating DFP-induced muscle fiber necrosis as evidenced by complete absence of lesions and the prevention of DFP-induced hyperactivity in nerve and muscle. Significant protection was afforded by all pretreatment agents when given alone. It is suggested that the pretreatment agents act presynaptically by preventing drug-induced backfiring and muscle fasciculations possibly by reducing the release of acetylcholine (ACh). The protective drugs in the concentrations used had no significant effect on the normal characteristics of conduction and transmission.


+1 Frameshifting as a novel mechanism to generate a cryptic cytotoxic T lymphocyte epitope derived from human interleukin 10.
Recent data indicate that some cytotoxic T cells (CTLs) recognize so-called cryptic epitopes, encoded by nonprimary open reading frame (ORF) sequences or other nonclassical expression pathways. We describe here a novel mechanism leading to generation of a cryptic CTL epitope. We isolated from the synovial fluid of a patient suffering from a Reiter's syndrome an autoreactive T cell clone that recognized cellular IL-10 in the HLA-B*2705 context. The minimal IL-10 sequence corresponding to nucleotides 379-408 was shown to activate this clone, upon cotransfection into COS cells with the DNA encoding HLA-B*2705, but the synthetic peptide deduced from this sequence did not stimulate the clone. Using a site-directed mutagenesis approach, we found that this clone recognized a transframe epitope generated by an internal +1 frameshifting in the IL-10 sequence and so derived partly from ORF1, partly from ORF2. We defined that +1 frameshifting was induced by a specific heptamer sequence. These observations illustrate the variety of mechanisms leading to generation of cryptic epitopes and suggest that frameshifting in normal cellular genes may be more common than expected.


[Palliative retrosternal reconstruction in cancer of the esophagus].
Among patients presenting with a cancer of the esophagus, only a third will have a theoretical radical resection. Out of our management: 1 - By pass with operatory abdominal and cervical check up--2 - Chemotherapy--3 - Total esophageal resection by thoracotomy, 29 patients get through the first stage only, which is then considered as a palliation method. Results obtained about the degree of palliation, i.e. quality of life, pathologic incidences, mortality rates are compared with other methods.


The Strength of Social Norms Across Human Groups.
Social norms are a defining feature of human psychology, yet our understanding of them is still underdeveloped. In this article, we present our own cross-cultural research program on tightness-looseness (TL)-which draws on field, experimental, computational, and neuroscience methods-to illustrate how going beyond Western borders is critical for understanding social norms' functions and their multilevel consequences. Cross-cultural research enables us to account for the universal features of norm psychology but also explains the great cultural diversity we see in social norms around the globe.


Investigation of the use of whey powder and buttermilk powder instead of skim milk powder in yogurt production.
The aim of this study was to determine some physical, chemical, microbiological and organoleptic properties of set-type yogurts made with six different skim milk powder (SMP), whey powder (WP) and buttermilk powder (BMP) during a 21-day period. Samples were taken from yogurts on day 1, 7, 14 and 21. Analyses were carried out on the total solids, fat, non-fat solids, protein, ash, viscosity, syneresis, pH, titratable acidity values. The counts of Streptococcus salivarius subsp. thermophilus, Lactobacillus delbrueckii subsp. bulgaricus and yeasts-molds were enumerated. Also, sensory evaluations were performed at the same times. The substitution effect of WP and BMP for SMP on ash, viscosity, syneresis and titratable acidity values of yogurts were found to be significant (p < 0.05), while total solids, non-fat solids, protein contents, pH value and S. thermophilus, L. bulgaricus and yeasts-molds counts were not statistically significant. The effect of storage period on protein, ash, viscosity, and titratable acidity values, and L. bulgaricus and yeasts-mold counts was found to be significant (p < 0.05) statistically. However, it was observed that the changes of total solids, fat, non-fat solids, syneresis, pH values, and S. thermophilus counts were insignificant during the storage period. The sensory evaluations showed that sample D was most preferred by panelists.


Bilateral lung transplantation for severe persistent and difficult asthma.
Although asthma is listed as an indication for lung transplantation, only 2 cases have been reported to date. Here, we describe a 42-year-old woman with progressive, severe, persistent bronchial asthma resistant to high-dose oral steroids and adjuvant immunosuppressive therapy. Because conventional and experimental therapeutic strategies failed, the patient was listed for bilateral lung transplantation and received a transplant shortly thereafter. At 12 months after transplantation, her lung function parameters are normal and an asthma attack has not occurred since.


Properties of carbohydrate-stripped thyroglobulin. III. Solubility characteristics of thyroglobulin.
In studying the solubility characteristics of thyroglobulin, it was found that the removal of sialic acid residues from either human or hog thyroglobulin by treatment with neuraminidase markedly decreased the solubility in salt solutions. On the other hand, naturally sialic acid-rich thyroglobulin obtained from human diffuse goiter was slightly more soluble than thyroglobulin in which sialic acid content was within the normal range. However, the desialized preparations prepared from both normal and sialic acid-rich thyroglobulin showed markedly lower solubility and further, showed no significant difference in solubility between them. These results indicate that the surface charge of thyroglobulin which influenced the salting-out property depends largely on the number of sialic acid residues in a thyroglobulin molecule, not on the degree of iodination of thyroglobulin.


FT-IR, FT-Raman, ab initio, HF and DFT studies, NBO, HOMO-LUMO and electronic structure calculations on 4-chloro-3-nitrotoluene.
In this work, the vibrational spectral analysis was carried out by using Raman and infrared spectroscopy in the range 100-4000 cm(-1) and 50-4000 cm(-1), respectively, for 4-chloro-3-nitrotoluene (C7H6NO2Cl) molecule. The molecular structure, fundamental vibrational frequencies and intensity of the vibrational bands are interpreted with the aid of structure optimizations and normal coordinate force field calculations based on Hartree Fock (HF) and density functional theory (DFT) method and different basis sets combination. The complete vibrational assignments of wavenumbers were made on the basis of potential energy distribution (PED). The scaled B3LYP/6-311++G(d,p) results show the best agreement with the experimental values over the other methods. The calculated HOMO and LUMO energies shows that charge transfer within the molecule. The effects due to the substitutions of methyl group, nitro group and halogen were investigated. The results of the calculations were applied to simulate spectra of the title compound, which show excellent agreement with observed spectra. Besides, frontier molecular orbitals (FMO), molecular electrostatic potential (MEP) and thermodynamic properties were performed.


Do changes in torsional magnetic resonance imaging reflect improvement in gait after femoral derotation osteotomy in patients with cerebral palsy?
Femoral derotation osteotomy (FDO) is commonly used to correct internal rotation gait (IRG) in spastic diplegia. The purpose of this study was to investigate whether the extent of intraoperative derotation is reflected in changes in static (clinical ROM and anteversion angle measured on torsional MRI) and dynamic parameters (transverse plane kinematics in three-dimensional gait analysis) after FDO in children with spastic diplegia. In a prospective study, 30 children with spastic diplegia and IRG were treated with FDO as part of a multilevel surgery and were examined pre- and postoperatively clinically, by three-dimensional gait analysis and by torsional MRI according to a standardised protocol. A correlation (r = 0.317, p = 0.015) between the extent of intraoperative derotation and mean hip rotation in stance as well as the anteversion angle measured on torsional MRI (r = 0.454, p < 0.001) was found. However, no significant correlation was observed between anteversion angle (tMRI) and mean hip rotation in stance, either before or after FDO. Significant improvements were found in IRG after FDO, confirming the results of previous studies. There was no correlation between the anteversion measured on MRI and the mean hip rotation in stance in 3D gait analysis before or after FDO. Thus, the data suggest that if the intraoperative extent of derotation is determined only by the anteversion angle, the result will not be better after FDO. It might only help to avoid retroversion and indicate the maximum amount of femoral derotation. In this study the extent of the intraoperative derotation was orientated at the preoperative midpoint of rotation. Based on the small, but significant correlation between the clinical midpoint and the mean hip rotation in stance in the gait analysis, determination of the intraoperative extent of derotation according to the mean hip rotation in stance seems to give the best results.


The effect of the alpha 2-adrenergic agonist, guanfacin, on the energy metabolism of steers fed on low-quality-roughage diets.
The effect of the alpha 2-adrenergic agonist, guanfacin, on the energy metabolism, feed intake and live weight (LW) change of steers was studied in three experiments. In the first, the metabolic rate of twelve steers was measured after a 72 h fast. The next day, after a 96 h fast, six steers were injected intramuscularly with 15 mg guanfacin in sterile saline (9 g sodium chloride/l) and six with sterile saline alone, and metabolic rate was measured again. Treatment significantly (P less than 0.01) lowered metabolic rate by approximately 20% (53.9 v. 66.8 kJ/kg per d). In the second experiment twelve steers were fed on long-chopped, low-quality roughage (Pangola grass (Digitaria decumbens) hay) ad lib. for 6 weeks. Six steers were continuously infused through a jugular catheter with 15 mg guanfacin/d (about 40 micrograms/kg LW) in sterile saline. The other six served as controls. There was no significant effect of treatment on feed intake (g dry matter (DM)/kg LW) or the rate of LW loss. Treatment significantly (P less than 0.05) increased the retention time of fluid (17.9 v. 22.1 h) in the alimentary tract. In the final experiment twenty-three steers were divided into four treatment groups and fed on long-chopped, low-quality roughage (Pangola hay). Treated animals were continuously infused with guanfacin at the rate of 20, 40 or 80 micrograms/kg LW per d. Control steers were not infused. At the end of the 6-week feeding period metabolic rate was measured after a 72 h fast. Regardless of dose, guanfacin significantly (P less than 0.01) lowered metabolic rate.(ABSTRACT TRUNCATED AT 250 WORDS)


Molecular interactions between lecithin and sphingomyelin. Temperature- and composition-dependent phase separation.
X-ray diffraction, scanning calorimetry, and polarizing light microscopy have used to determine the complete ternary phase diagram egg yolk lecithin/bovine brain sphingomyelin/water over the temperature range 10-44 degrees. The phase diagram shows that lateral separation of phospholipid bilayer phases can arise from variations in both composition and temperature. At 44 degrees in excess water, lecithin and sphingomyelin are miscible at all ratios in a lamellar liquid crystal bilayer phase. For samples containing greater than 33 mol % sphingomyelin, colling to 20 degrees results in the progressive lateral separation of an ordered chain sphingomyelin lamellar gel phase from the lecithin/sphingomyelin liquid crystal bilayer phase. At 20 degrees and below, the spingomyelin gel phase co-exists with an ordered bilayer phase, a stoichiometric peritectic molecular compound (66 mol % lecithin, 33 mol % sphingomyelin). Cooling mixtures containing less than 33 mol % sphingomyelin ultimately separates the compound from a lecithin liquid crystal bilayer phase containing small amounts of sphingomyelin. Although singificant variations in the lecithin/sphingomyelin ratio occur in normal and pathological membranes, at 37 degrees our results would suggest complete bilayer phase and lateral phase separation of the "ordered" sphingomyelin gel phase appears uplikely.


Ecology of Rhodococcus equi in horses and their environment on horse-breeding farms.
Quantitative culture of R. equi in the feces of dams and foals, in the air of the stalls and in the soil of the paddocks was carried out on three horse-breeding farms during the foaling season. The isolation rates of R. equi from the feces of dams from the 3 farms suddenly increased to approximately 80% at the end of March, when the snow in the paddocks finished melting, and remained at that level during April and May. The mean number of R. equi and the isolation rate of R. equi from the feces of dams on the farms were investigated for 5 weeks before and 5 weeks after delivery. During the 10 weeks, there were no differences in the isolation rate or in the mean number of R. equi from the feces of dams. R. equi was first isolated from the feces of the foals born in February and the middle of March at 3-4 weeks of age, on the other hand, it was first isolated from the feces of foals born in the end of March and April at 1-2 weeks of age. The number of R. equi in the soil collected from the paddocks used by dams during the winter was approximately 10(2)-10(4) g-1 of soil during the experiment. R. equi was isolated from the air in the stalls at the end of March and the number of R. equi in the air increased particularly on dry and windy days.(ABSTRACT TRUNCATED AT 250 WORDS)


Helicity-flux-driven α effect in laboratory and astrophysical plasmas.
The constraint imposed by magnetic helicity conservation on the α effect is considered for both magnetically and flow dominated self-organizing plasmas. Direct numerical simulations are presented for a dominant contribution to the α effect, which can be cast in the functional form of a total divergence of an averaged helicity flux, called the helicity-flux-driven α (Hα) effect. Direct numerical simulations of the Hα effect are presented for two examples-the magnetically dominated toroidal plasma unstable to tearing modes, and the flow-dominated accretion disk.


A collaborative clinical placement model for physiotherapy students results in equivalent (or greater) direct patient care activity than that delivered by physiotherapists alone: an observational study.
The demand for physiotherapy clinical placements is rising which requires innovative approaches and an understanding of clinical placement models. To determine physiotherapy student contribution to direct patient care activity during a collaborative clinical placement model. Secondary aims determined the impact of clinical area and clinical educator to student (CE:student) ratio and if a group of students could reach equivalent direct patient care activity of a junior or senior physiotherapist. Physiotherapy student, and junior and senior physiotherapist occasions of service (OOS) were collected from five Queensland Public Health Sector hospital information management systems from four physiotherapy clinical areas (i.e. cardiorespiratory, musculoskeletal, neurorehabilitation, and orthopedics). Number of days of clinical activity was recorded to provide average OOS/day. Across a 5-week clinical placement a group of physiotherapy students in a collaborative clinical placement model provided on average 10.6 OOS/day (95%CI 10.1-11.2). In three (75%) clinical areas, a group of students participating in higher CE:student ratios produced more OOS/day. Clinical area and CE:student ratio predicted 39% of the variance in student average OOS/day. On average a group of students reached the equivalent direct patient care activity of a junior and senior physiotherapist by week two of a 5-week clinical placement. Physiotherapy students in a collaborative clinical placement model met or exceeded the direct patient care activity of a physiotherapist, irrespective of clinical area and CE:student ratio.


Refractive results of radial keratotomy after 10 years.
We analyzed retrospectively the refractive and visual results of a cohort of patients who underwent radial keratotomy for myopia 10 years ago. Radial keratotomies using centripetal incisions were performed by the same surgeon in 1986 and 1987 to correct myopia of -0.75 to -10.00 diopters (D). Refractive and visual results were evaluated at 1 month and on average 10 years after surgery. Thirty-nine patients (71 eyes) underwent radial keratotomy. Mean spherical equivalent refraction before surgery was -3.90 D and after surgery was -0.50 D at 1 month and +0.13 D at 10 years after surgery. At last examination, 41 eyes (43.7%) had a spherical equivalent refractive error within +/- 1.00 D of emmetropia (24 eyes [34%] +/- 0.50 D) and 32.4% of eyes were overcorrected by more than 1.00 D. Between 1 month and 10 years after surgery, a hyperopic shift greater than 1.00 D occurred in 34.1% of eves with a single procedure. Ten years after surgery, 59 eyes (83%) had uncorrected distance visual acuity of 20/40 or better (22 eyes [31%] with uncorrected visual acuity of 20/20 or better). This retrospective evaluation confirms that radial keratotomy is an effective procedure to correct myopic error, but the hyperopic shift produces an unstable, less predictable refraction in one-third of eyes at 10 years.


Wedge resection as an alternative treatment for octogenarian and older patients with early-stage non-small-cell lung cancer.
Anatomical resection with lymph node dissection is the standard treatment for early non-small cell lung cancer, whereas wedge resection is considered as a compromise. We aimed to determine whether wedge resection without lymph node dissection could be a treatment option for patients aged ≥80 years. We assessed 669 patients with clinical stage IA non-small cell lung cancer, whole tumour sizes ≤2 cm and a consolidation to tumour ratio of >0.5 who underwent R0 resection at three institutions between 2010 and 2016. We selected 58 of them who were aged ≥80 years and analysed their clinicopathological findings and prognosis after surgical procedures over a median follow-up of 38 months. Propensity scores for surgical procedures were calculated using age, gender, smoking status and solid tumour size on computed tomography. Three-year overall and recurrence-free survival rates after wedge resection and after segmentectomy + lobectomy for patients aged ≥80 years did not significantly differ (overall survival: 88.9% [95% confidence interval, 69.4-96.3%] vs. 75.5% [95% confidence interval, 51.5-88.8%], P = 0.95; recurrence-free survival: 85.2% [95% confidence interval: 65.2-94.2%] vs. 68.0% [95% confidence interval, 44.4-83.2], P = 0.57). Multivariable Cox regression analysis of overall survival with propensity scores revealed that surgical procedure was not an independent predictor of a poor prognosis (hazard ratio: 0.86 (0.28-2.6), P = 0.78) in patients aged ≥80 years. Wedge resection might be an alternative to lobectomy or segmentectomy with lymph node dissection for patients aged ≥80 years with early non-small cell lung cancer.


MicroRNA-129-5p-regulated microglial expression of the surface receptor CD200R1 controls neuroinflammation.
CD200R1 is an inhibitory surface receptor expressed in microglia and blood macrophages. Microglial CD200R1 is known to control neuroinflammation by keeping the microglia in resting state, and therefore, tight regulation of its expression is important. CCAAT/enhancer-binding protein β (CEBPβ) is the known regulator of CD200R1 transcription. In the present study, our specific intention was to find a possible posttranscriptional regulatory mechanism of CD200R1 expression. Here we investigated a novel regulatory mechanism of CD200R1 expression following exposure to an environmental stressor, arsenic, combining in silico analysis, in vitro, and in vivo experiments, as well as validation in human samples. The in silico analysis and in vitro studies with primary neonatal microglia and BV2 microglia revealed that arsenic demethylates the promoter of a microRNA, miR-129-5p, thereby increasing its expression, which subsequently represses CD200R1 by binding to its 3'-untranslated region and shuttling the CD200R1 mRNA to the cytoplasmic-processing body in mouse microglia. The role of miR-129-5p was further validated in BALB/c mouse by stereotaxically injecting anti-miR-129. We found that anti-miR-129 reversed the expression of CD200R1, as well as levels of inflammatory molecules IL-6 and TNF-α. Experiments with a CD200R1 siRNA-induced loss-of-function mouse model confirmed an miR-129-5p→CD200R1→IL-6/TNF-α signaling axis. These main findings were replicated in a human cell line and validated in human samples. Taken together, our study revealed miR-129-5p as a novel posttranscriptional regulator of CD200R1 expression with potential implications in neuroinflammation and related complications.


Minimizing the role of fusion in the rigid flatfoot.
The goals of surgery for the rigid flatfoot are to achieve a painless, stable, functional plantigrade foot. Although triple arthrodesis affords predictable correction and pain relief, the long-term sequelae of extended hindfoot fusions include arthritis and often the need for further, more extensive fusion procedures. We propose that satisfactory results can be achieved in the rigid flatfoot by limiting fusion to joints that are arthritic, and correcting associated deformity with osteotomy and soft tissue reconstruction.


Reduced expression of ribosomal proteins relieves microRNA-mediated repression.
MicroRNAs (miRNAs) regulate physiological and pathological processes by inducing posttranscriptional repression of target messenger RNAs (mRNAs) via incompletely understood mechanisms. To discover factors required for human miRNA activity, we performed an RNAi screen using a reporter cell line of miRNA-mediated repression of translation initiation. We report that reduced expression of ribosomal protein genes (RPGs) dissociated miRNA complexes from target mRNAs, leading to increased polysome association, translation, and stability of miRNA-targeted mRNAs relative to untargeted mRNAs. RNA sequencing of polysomes indicated substantial overlap in sets of genes exhibiting increased or decreased polysomal association after Argonaute or RPG knockdowns, suggesting similarity in affected pathways. miRNA profiling of monosomes and polysomes demonstrated that miRNAs cosediment with ribosomes. RPG knockdowns decreased miRNAs in monosomes and increased their target mRNAs in polysomes. Our data show that most miRNAs repress translation and that the levels of RPGs modulate miRNA-mediated repression of translation initiation.


The presence of steatosis and elevation of alanine aminotransferase levels are associated with fibrosis progression in chronic hepatitis C with non-response to interferon therapy.
Interferon (IFN) therapy leads to regression of hepatic fibrosis in chronic hepatitis C patients who achieve a sustained virologic response (SVR), while the beneficial effect is limited in those who fail to do so. The aim of the present study was to define factors associated with progression of fibrosis in patients who do not achieve a SVR. Fibrosis staging scores were compared between paired liver biopsies before and after IFN in 97 chronic hepatitis C patients who failed therapy. The mean interval between biopsies was 5.9 years. Factors associated with progression of fibrosis were analyzed. Fibrosis progressed in 23%, remained unchanged in 47% and regressed in 29%. Steatosis and a high average alanine aminotransferase (ALT) between biopsies were independent factors for progression of fibrosis with risk ratios of 5.53 and 4.48, respectively. Incidence and yearly rate of progression of fibrosis was 64% and 0.22+/-0.29 fibrosis units per year in those with both risk factors compared to 8% and -0.04+/-0.17 fibrosis units per year in those negative for both factors. Hepatic steatosis and elevated ALT levels are risk factors for progression of fibrosis in chronic hepatitis C patients who fail to achieve a SVR to IFN therapy and therefore may be therapeutic targets to halt the potentially progressive disease.


Lymphoscintigraphic drainage of acral limb skin to interval sentinel lymph nodes in healthy subjects.
In the literature, drainage to epitrochlear and popliteal sentinel lymph nodes (SLN) are analyzed for whole or distal extremity (below elbow or knee) melanomas that are not topographically homogeneous with respect to tendency of drainage to interval SLNs. We hypothesize that acral (hand and foot) skin has a uniform frequency of drainage to interval SLNs, which is higher than reported for distal extremity melanomas. One hundred healthy subjects were enrolled. Fifty subjects had standard four extremity lymphoscintigraphies by radiocolloid injection into an interdigital web space as in lymphodynamic studies. On another 50 subjects, either targeted upper (n = 25) or lower (n = 25) extremity lymphoscintigraphies were performed utilizing injection sites that likely drain to interval SLNs. Acral skin drainage to interval SLNs was analyzed for interindividual variability and injection site dependence. There was considerable interindividual variability in drainage of each injection site to interval SLNs. Hand skin had a uniform 50% frequency of drainage to epitrochlear-midhumeral SLNs with both injection sites. This frequency was higher than the epitroclear SLN frequencies reported for distal extremity melanomas. Foot skin had 10% and 90% frequencies of drainage to popliteal SLNs from standard and targeted injection sites, respectively. Foot skin largely simulates the tendency of drainage reported for distal extremity melanomas while lateral heel represents a limited zone that almost uniformly drains to popliteal SLNs. Despite dissimilarities between hand and foot, acral skin drainage to interval SLNs is high enough to obligate a thorough interval SLN exploration in acral primaries.


Study on stability mechanism of immobilized pH gradient in isoelectric focusing via the Svensson-Tiselius differential equation and moving reaction boundary.
An immobilized pH gradient (IPG) has strong power against instability (e.g., drifting and plateau) existing in classic isoelectric focusing (IEF). However, the relevant mechanism against the instability of pH gradient is still unclear. In this work, the theories of diffusional current and water products in IEF were developed based on the Svensson-Tiselius's differential equation and concept of moving reaction boundary (MRB). Two novel methods of pH gradient mobilization in IPG-IEF and non-IPG-IEF (opposite to IPG-IEF) were developed to unveil stability mechanism of IPG-IEF. The theoretical and experimental results indicated that (i) the drifting of pH gradient in non-IPG-IEF could be effectively controlled by IPG technique due to the existence of equal-fluxes of hydroxyl and hydrogen ions in the IPG-IEF system, (ii) there existed high diffusional current in non-IPG-IEF because of the existence of free carrier ampholyte (CA), but weak current in the IPG-IEF due to the immobilization of CA species in gel matrix, and (iii) the high diffusional current resulted in a great amount of water formation in neutral zone of pH gradient that led to distinct plateau in non-IPG-IEF, conversely the weak diffusional current caused little of water formation and weak plateau of pH gradient in IPG-IEF. These studies have considerable significance to the understanding of mechanism and development of protein IEF separation technique.


Management of a localized prostatic adenocarcinoma despite the very high rate of PSA and the large tumor mass: Does PSA level indicate the stage of prostate cancer?
Prostate-specific antigen (PSA) is a marker specific to the prostate gland, and it is, therefore, possible to observe an increase in PSA above 4 ng/mL in cases of benign prostatic hypertrophy and cancer. But according to studies, a very high PSA level is most likely synonymous with metastatic prostate cancer. Our rare case concerns the management of a localized prostatic adenocarcinoma despite a very high PSA level of over 3000 ng/mL, with an enormous volume of prostate without invasion or distant metastasis. A very high PSA level can probably be a sign of metastatic prostatic adenocarcinoma, but not necessarily.


Using fetal acoustic stimulation to shorten the biophysical profile.
To determine whether fetal acoustic stimulation can decrease the time required to achieve a reassuring biophysical profile. Patients scheduled for a biophysical profile were prospectively assigned to study and control groups. The study group received 3 seconds of acoustic stimulation if fetal breathing, tone, or movement were not present during the first 5 minutes of the study. The biophysical profile was completed in the standard fashion, for both groups. A total of 870 patients were enrolled (458 control, 412 with stimulation). The fetal acoustic stimulation group had decreased testing time (3 minutes) and fewer non-reassuring tests (5%). The fetal acoustic stimulation group had fewer studies without breathing, potentially reducing the need for further testing or intervention. Fetal acoustic stimulation can be used to decrease the biophysical profile testing time and to reduce the number of non-reassuring tests.


Destabilization of β-amyloid aggregates by thrombin derived peptide: plausible role of thrombin in neuroprotection.
β-amyloid (Aβ) aggregates involved in Alzheimer's disease (AD) are resistant to proteases but could be destabilized by small peptides designed to target specific hydrophobic regions of Aβ that take part in aggregate assembly. Since thrombin and AD are intricately connected, and elastase modulates thrombin activity, elastase-digested thrombin peptides were verified for intervention in the Aβ-aggregation pathway. Intact or elastase-digested thrombin destabilized Aβ fibril, as demonstrated by thioflavin T assay. Peptides were synthesized employing thrombin as a template, of which, a hexapeptide (T3) showed maximum destabilization at 1 µm. ExPASy peptide cutter software coupled with mass spectrometric analysis confirmed the generation of T3 peptide from elastase-digested thrombin. TEM micrographs revealed that 30-day incubation of preformed Aβ fibrils or monomers with T3 resulted in destabilization or inhibition, respectively, leading mostly to particles of 1.74 ± 0.17 nm, which roughly corresponded to Aβ monomer. Surface plasmon resonance employing CM5 chip coupled with Aβ40 mouse monoclonal antibody showed a drop in response when T3 was incubated with Aβ fibrils between 2 and 8 h. 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide and confocal microscopy demonstrated the ability of T3 to rescue neuroblastoma cells from Aβ oligomer-induced cytotoxic damage. Although no [Aβ-T3] adduct could be detected by mass spectrometry, an initial interaction appeared to facilitate the process of destabilization/inhibition of aggregation. T3 was comparable to standard β-sheet breaker peptides, LPFFD and KLVFF in terms of Aβ aggregate destabilization. High hydrophobicity values coupled with recognition and breaking elements make T3 a potential candidate for future therapeutic applications.


A novel oxidative transformation of alcohols to nitriles: an efficient utility of azides as a nitrogen source.
An efficient methodology to oxidize benzylic and cinnamyl alcohols to their corresponding nitriles in excellent yields has been developed. This methodology employs DDQ as an oxidant and TMSN(3) as a source of nitrogen in the presence of a catalytic amount of Cu(ClO(4))(2)·6H(2)O.


Measles-mumps-rubella immunization of susceptible hospital employees during a community measles outbreak: cost-effectiveness and protective efficacy.
To determine cost-effectiveness and protective efficacy of a program to identify and immunize susceptible hospital employees during a measles outbreak. A cost analysis was made of blind measles-mumps-rubella (MMR) immunization versus directed MMR immunization based on 2,000 employees born after December 31, 1956. A directed MMR immunization program for susceptible employees was instituted. Actual costs of the program were calculated at the conclusion of the program. A medical center complex with more than 4,000 employees, two acute care community hospitals, and a tertiary care children's hospital. A directed MMR immunization program was projected to be less expensive than blind immunization ($23,106 versus $70,720). MMR vaccine was administered to 169 of 188 susceptible employees. Actual cost of the directed MMR immunization program was $25,384. The directed MMR immunization program was cost-effective and prevented secondary cases among hospital employees during a community measles outbreak.


[Cervical smears in general medicine. Evaluation of the regular performance of cervical smears among the patients of general practitioners in the Rhône-Alpes region].
Cervical smears in the area of "Rhône Alpes" are evaluated through a population examined by general practitioners. Among 10,000 examined women, aged from 15 to 69 years, 20% had never been smeared. In 8% of the remaining 8,000 cases, the smear was realized since more than 5 years. Absence or prolonged delay was more frequently met with more aged women, from unfavorable or rural area; or foreigner (from South of Europe or from North-West Africa). These results are discussed and compared with those of other studies whether inside or outside France. Certainly, they are under-estimated as regards the general population. In fact, this study considers an already mostly medicalized population together with volunteer general practitioners. However, it's always less medicalized than in most of French studies considering this subject.


Does Life Expectancy Affect Treatment of Women Aged 80 and Older with Early Stage Breast Cancers?
BACKGROUND: Data are needed on how life expectancy affects treatment decisions among women ≥80 years with early stage breast cancer. METHODS: We used the linked Surveillance Epidemiology and End Results-Medicare claims dataset from 1992-2005 to identify women aged ≥80 newly diagnosed with lymph node negative, estrogen receptor positive tumors, ≤5 centimeters. To estimate life expectancy, we matched these women to women of similar age, region, and insurance, not diagnosed with breast cancer. We examined 5-year mortality of matched controls by illness burden (measured with the Charlson Comorbidity Index [CCI]) using Kaplan-Meier statistics. We examined treatments received by estimated life expectancy within CCI levels. We further examined factors associated with receipt of radiotherapy after breast conserving surgery (BCS). RESULTS: Of 9,932 women, 39.6% underwent mastectomy, 30.4% received BCS plus radiotherapy, and 30.0% received BCS alone. Estimated 5-year mortality was 72% for women with CCIs of 3+, yet 38.0% of these women underwent mastectomy and 22.9% received radiotherapy after BCS. Conversely, estimated 5-year mortality was 36% for women with CCIs of 0 and 26.6% received BCS alone. Age 80-84, urban residence, higher grade, recent diagnosis, mammography use, and low comorbidity, were factors associated with receiving radiotherapy after BCS. Among women with CCIs of 3+ treated with BCS, 36.9% underwent radiotherapy. CONCLUSIONS: Many women aged ≥80 with limited life expectancies receive radiotherapy after BCS for treatment of early stage breast cancers while many in excellent health do not. More consideration needs to be given to patient life expectancy when considering breast cancer treatments. KEY WORDS: Breast cancer, older women, treatment, life expectancy, radiation.


Influence of nutritional status on basal metabolic rates among rural agriculturalists of Ngilo-Ilo, East Java.
Previous research has shown that tropical island populations have reduced basal metabolic rates (BMR) associated with the joint influences of heat stress and undernutrition. This study examines variation in BMR among an indigenous population of Indonesia, and compares these data with those collected from earlier studies in Indonesia. Anthropometric dimensions and BMR were measured on a sample of 35 Indonesian adults (28 men, 7 women) from the rural village of Ngilo-Ilo, East Java. Mean measured BMRs (±SD) were 1433 ± 344 kcal/d in men and 1256 ±257 kcal/d in women, and were not significantly different from estimates using the FAO/WHO/UNU predictive questions. Underweight individuals (BMIs <18.5 kg/m2 ) had BMRs that were 7.6% below predicted levels, while those with BMIs ≥18.5 kg/m2 had BMRs that were 8.0% above predicted levels (P < .01). Underweight individuals also had significantly higher respiratory quotients (RQ = .94 vs. .89; P < .05), suggesting lower levels of fat oxidation. Compared to data from previous studies (1929-1979), men of the Ngilo-Ilo sample had similar BMIs (19.8 vs. 19.2 kg/m2 ), but higher BMRs, after adjusting for age and body weight (+2.1% vs. -5.6%; P < .05). Among the agriculturalists of Ngilo-Ilo, measured BMRs were low, but not significantly different from those predicted by the FAO/WHO/UNU equations. Among subjects of this sample and from earlier studies, poorer physical nutritional status was associated with reduced BMRs. These results suggest that chronic energy stress has consistently shaped metabolic function among Indonesian rural populations.


(E)-3-{4,6-Dimeth-oxy-2-[(E)-4-meth-oxy-styr-yl]-3-methyl-phen-yl}-1-(2-hy-droxy-5-meth-oxy-phen-yl)prop-2-en-1-one.
In the title compound, C28H28O6, the benzene rings in the resveratrol moiety are connected by a trans C=C double bond, and the hydroxyl group containing a benzene ring and the central benzene ring are linked through a C=(O)-C=C (enone) moiety to form a chalcone unit. An intra-molecular O-H⋯O hydrogen bond generates an S(6) ring motif. In the crystal, pairs of C-H⋯O hydrogen bonds generate dimers and additional weak C-H⋯O inter-actions link the dimers into chains propagating along the b-axis direction.


Differentiating the 2,3-diols of glucopyranosides by 4,6-O-benzylidene-protected-1,2-D-glucopyranosylorthoesters strategy.
A facile and efficient method to differentiate the 2,3-diols of glucopyranosides based on 1,2-orthoesters strategy was developed. Stable thioglucosides were employed as the starting materials to prepare the corresponding 1,2-orthoesters. When treated with HCl aqueous solution and followed with Et(3)N, differentiation of the 2,3-diols was efficiently achieved along with the generation of a convertible anomeric hydroxyl group. In addition, an easy and practical method based on NOE was proposed to determine whether the 1,2-orthoesters were endo-type or exo-type.


Multiresidual analysis of emerging amphetamine-like psychoactive substances in wastewater and river water.
Besides the common illicit drugs, such as cocaine, heroin, and marijuana, there is a growing concern about the use of modern "designer drugs" that have emerged in large numbers over the past few years. In this work, a sensitive and selective method for simultaneous determination of 25 synthetic amphetamine-like psychoactive compounds, including amphetamine, sympathomimetic substituted amphetamines, synthetic cathinones and ketamine, in raw wastewater (RW), secondary effluent (SE) and river water was developed. Samples were enriched by solid-phase extraction (SPE) on mixed-mode reversed-phase/strong cation-exchange sorbent (Oasis MCX) and analysed by reversed-phase liquid chromatography coupled to electrospray ionisation tandem mass spectrometry (LC-MS/MS). The target compounds were separated on a Synergi Polar column and detected using multiple reaction monitoring (MRM) in positive ionisation mode. Accurate quantification was achieved by using several deuterated analogues as surrogate standards. Careful optimisation and validation of the procedure resulted in a reliable determination of all target analytes in low ng/L range for all matrices, which makes the method suitable for the application in wastewater-based epidemiology. The method was applied for assessment of selected compounds in municipal wastewater and river water from Croatia. It was shown that most of the wastewater samples contained detectable levels of the well-known synthetic illicit drugs, amphetamine and 3,4-methylenedioxy-methamphetamine (MDMA) (concentrations up to 545ng/L and 55ng/L in RW, respectively), as well as ephedrine (up to 108ng/L) and pseudoephedrine (up to 698ng/L), which are used as ingredients of popular over-the counter cough and cold medications. Other target amphetamine-like psychoactive substances, recently reported for their potential abuse, were detected only occasionally and in low concentrations (<10ng/L).