Prolonged Study Period Research Articles

The selective NOX4 inhibitor GLX7013159 decreases blood glucose concentrations and human beta-cell apoptotic rates in diabetic NMRI nu/nu mice transplanted with human islets

NADPH oxidase 4 (NOX4) inhibition has been reported to mitigate diabetes-induced beta-cell dysfunction and improve survival in vitro, as well as counteract high-fat diet-induced glucose intolerance in mice. We investigated the antidiabetic effects of the selective NOX4 inhibitor GLX7013159 in vivo in athymic diabetic mice transplanted with human islets over a period of 4 weeks. The GLX7013159-treated mice achieved lower blood glucose and water consumption throughout the treatment period. Furthermore, GLX7013159 treatment resulted in improved insulin and c-peptide levels, better insulin secretion capacity, as well as in greatly reduced apoptotic rates of the insulin-positive human cells, measured as colocalization of insulin and cleaved caspase-3. We conclude that the antidiabetic effects of NOX4 inhibition by GLX7013159 are observed also during a prolonged study period in vivo and are likely to be due to an improved survival and function of the human beta-cells.

Number of COVID-19 cases required in a population to detect SARS-CoV-2 RNA in wastewater in the province of Alberta, Canada: Sensitivity assessment

With a unique and large size of testing results of 1,842 samples collected from 12 wastewater treatment plants (WWTP) for 14 months through from low to high prevalence of COVID-19, the sensitivity of RT-qPCR detection of SARS-CoV-2 RNA in wastewater that correspond to the communities was computed by using Probit analysis. This study determined the number of new COVID-19 cases per 100,000 population required to detect SARS-CoV-2 RNA in wastewater at defined probabilities and provided an evidence-based framework of wastewater-based epidemiology surveillance (WBE). Input data were positive and negative test results of SARS-CoV-2 RNA in wastewater samples and the corresponding new COVID-19 case rates per 100,000 population served by each WWTP. The analyses determined that RT-qPCR-based SARS-CoV-2 RNA detection threshold at 50%, 80% and 99% probability required a median of 8 (range: 4-19), 18 (9-43), and 38 (17-97) of new COVID-19 cases /100,000, respectively. Namely, the positive detection rate at 50%, 80% and 99% probability were 0.01%, 0.02%, and 0.04% averagely for new cases in the population. This study improves understanding of the performance of WBE SARS-CoV-2 RNA detection using the large datasets and prolonged study period. Estimated COVID-19 burden at a community level that would result in a positive detection of SARS-CoV-2 in wastewater is critical to support WBE application as a supplementary warning/monitoring system for COVID-19 prevention and control.

Korelasi Indeks Prestasi Kumulatif dan Masa Studi dengan Uji Kompetensi Perawat

Nursing competency test is a process that must be passed by nursing students to measure the suitability between knowledge, skills and student behavior against competency standards of graduates who meet work competency standards. Only students who pass the competency test are able to enter health services. Passing competency test is certainly influenced by various aspects, some of them are GPA and study period. Both of these things are an important role in the teaching and learning process that a student goes through. GPA is an indicator to assess learning achievement and the length of study is the time taken by the student to complete his studies. However, recently there has been an assumption among students that a high GPA does not guarantee in passing competency test and a prolonged study period does not prevent students from first passing the competency test, therefore researchers are interested in seeing the correlation of the two things. Objective The aim of the reasearch was to determine the correlation between Grade Point Average (GPA) and the period of study toward passing the Nursing Competency Test in Nursing Departement of the Health Polytechnic of the Ministry of Health in Mamuju. Method This research is an analytic study with cross sectional design using secondary data. This research used total sampling with a sample size of 138. The Result showed that GPA had p<0,001 with correlation r= 0,908 and the study period had p<0,001 with correlation r=0,291. The Conclusion of the research is GPA had positive corelation very strong and the study period also had positive corelation but poor corelation.

Effect of Long-Term Hydroxytyrosol Administration on Body Weight, Fat Mass and Urine Metabolomics: A Randomized Double-Blind Prospective Human Study

Hydroxytyrosol (HT) is a natural antioxidant found in olive products and characterized by well-documented beneficial effects on human health. Several research studies are ongoing that aim to investigate its potency and molecular mechanism of action. The present study aimed to investigate the potential effect of HT on human obesity through a randomized double-blind prospective design. HT in two different doses (15 and 5 mg/day) and a placebo capsule was administered to 29 women with overweight/obesity for six months and their weight and fat mass were monitored at three time points (baseline, 4, 12 and 24 weeks). Statistically significant weight and visceral fat mass loss (%weight loss: p = 0.012, %visceral fat loss: p = 0.006) were observed in the group receiving the maximum HT dosage versus placebo after 4 weeks of the intervention, with attenuation of these findings at 12 and 24 weeks of the study. Urine samples were collected during the intervention and analyzed via liquid chromatography–high-resolution mass spectrometry for untargeted metabolomic purposes and comparisons between study groups were performed. HT administration was safe and well-tolerated. To the best of our knowledge, this is the first human cohort investigating the effects of HT on obesity for a prolonged study period.

Saudi Arabia and Indonesian Networks: Migration, Education, and Islam By Sumanto Al Qurtuby

This study investigates a specific type of transregional ties, namely those between Saudi Arabia and Indonesia in the field of education. While the title refers to the current nation-states, Al Qurtuby’s study offers a longue-durée perspective by integrating the centuries-old tradition of Muslim pilgrimage in combination with prolonged periods of study in the holy cities and other nodes of the pilgrimage route. Such alternative Muslim centres of learning, most notably in Yemen, Egypt and Turkey, also re-appear from time to time in the narrative, thus widening the scope of the study beyond its main subject matter. Al Qurtuby sets the scene by first providing an overview of Arabian–Indonesian relations, starting from the pilgrimage and traditional Islamic learning that has expanded to Indonesians attending many different types of educational institutions in the Kingdom of Saudi Arabia. He also refers to the large-scale labour migration to the Peninsula that has impacted on the otherwise positive image of Indonesians who, until the 1980s, had been mostly perceived as students of Islam. Finally, he broaches the topic of the current diplomatic rapprochement marked by the visit of Indonesian President Joko Widodo in Riyadh in 2015 and the return visit, in 2017, by King Salman in Jakarta. The author concludes this overview by emphasizing education, religion and employment as the main motives of Indonesians to travel to Saudi Arabia.

Civic and Political Engagement during the Multifaceted COVID-19 Crisis.

Measures to cope with the COVID‐19 pandemic have put a sudden halt to street protests and other forms of citizen involvement in Europe. At the same time, the pandemic has increased the need for solidarity, motivating citizens to become involved on behalf of people at risk and the vulnerable more generally. This research note empirically examines the tension between the demobilisation and activation potential of the COVID‐19 crisis. Drawing on original survey data from seven Western European countries, we examine the extent, forms, and drivers of citizens’ engagement. Our findings show the remarkable persistence of pre‐existing political and civic engagement patterns. Concurrently, we show that threat perceptions triggered by the multifaceted COVID‐19 crisis have mobilized Europeans in the early phase of the pandemic. Similarly, the role of extreme ideological orientations in explaining (regular) political engagement indicates that the current situation may create its specific mobilisation potentials.

Perceptions of medical college academics on intercalated MBBS/BSc dual degree program in Nigeria

Purpose: The purpose of this study was to determine the perceptions of academics on the acceptability of the intercalated medical degree program in an attempt to proffer solutions to breach the gaps in manpower shortages in the medical profession.Methodology: This is a descriptive cross sectional survey. Randomly selected 150 academic staff of various medical colleges spread across Nigeria, who attended an educational programme in Abuja Nigeria in September 2018 completed semi structured questionnaires after consenting to participate in the study. Data from the retrieved questionnaires were collated, entered into Microsoft excel and analyzed using descriptive statistics. Most of the analyzed data were represented in percentages for ease of comparison.Findings: Sixty five percent of the respondents were aware of the intercalated (dual) Bachelor of Medicine, Bachelor of Surgery (MBBS)/ Bachelor of Science (B.Sc.) degree programme, offer it in their institutions and believe it is worthwhile. The merits of the dual degree programme from this study were an additional degree, more experienced medical doctors in terms of research and exit strategy for some medical students who may change their minds half way into the medical programme. The disadvantages reported were prolonged study period and increased cost of study. Majority of the respondents, who were academic staff of medical colleges were aware of, and favoured the establishment of intercalated MBBS degree programme in more Nigerian medical colleges.Unique contribution to theory, practice and policy: There is scarcity of literature on the intercalated degree programme in Nigeria. This research may influence policy change that will improve medical education. From the results of the study, it is recommended that the stakeholders in medical education should consider giving accreditation to more medical colleges that have the capacity to commence intercalated medical degree programs in Nigerian Universities as an option to interested medical students with good potentials.

Noise Exposure on the London Underground, an Observational Study over a Decade.

There are no hearing protection regulations in place for passengers using public transport, such as the London Underground. In light of this, we sought to examine sound pressure levels experienced by regular users of the London Underground. Sound pressure levels (A-weighted decibels: dBA) were taken on moving London Underground carriages between Euston and South Wimbledon on the Northern Line, and between Euston and Vauxhall on the Victoria Line, during 2006 and 2018. In addition, carriage sound pressure levels travelling within Zone 1 of the London Underground were tested in 2019. Three experimental and three technical repeats were undertaken using a hand-held calibrated multi-function sound level meter. Passengers are routinely and consistently subjected to sound pressure levels exceeding 80 dBA, with levels sometimes reaching over 100 dBA. This study is unique within the literature, with no published studies outlining exposure levels for London Underground passengers. It provides evidence of elevated noise exposure to passengers, consistently along large stretches of the London Underground, over a prolonged study period (2006-2019). Sensorineural hearing losssound pressureexposureLondonundergroundtube. N/A Laryngoscope, 2020.

Contrasting changes in snow cover and its sensitivity to aerosol optical properties in Hindukush-Karakoram-Himalaya region

Snow cover plays a major role in the earth's climate system. The stability of the snow mass over Hindukush-Karakoram-Himalaya (HKH) in contrast to the worldwide retreat of mountainous glaciers and its relation to aerosol concentration remains poorly understood. The proposed study focused on the understanding of this relationship between various snow parameters and the optical properties of atmospheric aerosols over the HKH region of Northern Pakistan between March and June for a prolonged study period from 2005 to 2015. The aerosol's optical properties were retrieved from snow covered pixels in the study area to avoid the contamination of snow albedo (SA) by other features of land surfaces. The results revealed an increasing trend in the snow cover area (SCA) at the rate of 577.3, 1090.6 and 652.3 km2/year in March, May and June, respectively, with a decrease in April due to the uneven distribution of SCA during 2005–2015. The results revealed a strong positive correlation (R = 0.77) between SCA and SA, whereas SCA and SST were negatively correlated (R = −0.82) during the study period. The Cloud-Aerosol Lidar and Infrared Pathfinder (CALIPSO) indicated the presence of scattering and absorbing aerosols (e.g., dust, polluted dust, and smoke) both at high and low altitudes. However, the diminution of aerosol concentration was caused by their short time span in atmosphere and the occurrence of snowfall that washed them out from the snow at high altitudes. The findings indicated an increased SCA, with contrasting behavior in the ablation period. However, the presence of aerosols demands proper attention, to monitor any future threat to the high-altitude cryosphere.

The burden of muscle injuries in youth football

Background: Muscle injuries affect up to 72% of professional soccer players within one season and there are well reviewed, but muscle injuries in youth soccer players are not widely documented. The aim of this study was to investigate incidence, localization, pathomechanism and point of time of indirect muscle injuries in youth soccer players. Methods: Prospective cohort study. 5 teams (U15, U16, U17, U18 and U21) with 110 young male football players (age 16,8 (14,3–21) years, height 174,5 (146,1–190,0) cm, weight 65,7 (35,5–84,6) kg) were monitored for 12 months. Every muscle injury was documented and monitored on a standardized evaluation score. Results: In total, 53 muscle injuries were registered. On average, a player sustained 0,4 muscle injuries per season. There was only one re-injury (2%). The injury rate was 1,5 injuries per 1000h match- or /training hours, the match injury rate (6,9) being 7,7 times higher than the training injury rate (0,9). Sixty-nine percent were functional muscle injuries. Thirty-seven percent of all muscle injuries affected the hamstrings group and twenty-eight percent the adductors. The most common pathomechanism was overload (28%). Most of the injuries were recorded during the last 15 minutes of a game or a training (39,6%). Conclusion: Muscle injuries are a substantial problem for players and clubs, also in young male football players. This study confirmed previous results showing that the injury rate during games is higher than during trainings and that hamstrings injuries are the most common muscle injuries in soccer. However, a prolonged study period is recommended to gain better statistical values.

Effects of Foot Bath on Leg Edema and Fatigue among College Students

Purpose: This study was conducted to examine the effect of foot-bath on lower extremities edema and fatigue among college students in Korea. Methods: This study used an quasi-experimental design with 56 participants (30 for experiments and 26 for controls). The experimental group performed 20-minute foot bath before sleep three times for one week. All subjects were directed to use their smart-phones to fill out a questionnaire about fatigue. Leg circumference was measured 10 minutes after foot bath. The test was performed from April 30th to May 22th in 2016. Data was analyzed using t-test and x2 test. Results: We found no difference in general characteristics between the experimental group and the control group. Left leg edema of the experimental group decreased by 16.63±14.57 mm (p<.001). The experimental group's right leg-edema decreased by 13.10±13.97 mm (p<.001). There was no statistically significant difference in their fatigue level when comparing before and after the foot baths. Conclusion: We found that doing foot baths for two weeks could have positive effects in reducing leg-edema among college students. Foot bath may be applied as an effective nursing intervention to decrease leg edema among young people. The results are based on a limited number of study samples and a short-term intervention. Further research can be performed with extended population and a prolonged study period.

Bioindicator Thais carinifera (mollusca, gastropoda): imposex response and consequences along the Pakistan coast during the period from 1993 to 2012

Abstract Endocrine mediated "imposex" phenomenon was investigated and recorded in the muricoid gastropod species Thais carinifera during the two decades from 1993 to 2012 at three (3) sites out of six (6) localities investigated along the Sindh and Balochistan coast, Pakistan. The VDS stages 1 to 4 were apparent in Thais carinifera. The intensity of imposex has remained comparatively low in the populations of harbours in close proximity to port Mohammad Bin-Qasim, namely; Old Korangi Fish Harbour (OKFH) and New Korangi Fish Harbour (NKFH) where shipping activities are sporadic as compared to those in Manora Channel and the adjoining Karachi Port area where intensive shipping activity is rather frequent. Target species found to be good bioindicators have shown a marked decrease over the prolonged study period. Investigations show that this decrease is solely due to globally imposed effective bans on tributyltin (TBT) based antifouling paints over the past decade.

Changes in Individual Drug-Independent System Parameters during Virtual Paediatric Pharmacokinetic Trials: Introducing Time-Varying Physiology into a Paediatric PBPK Model

Although both POPPK and physiologically based pharmacokinetic (PBPK) models can account for age and other covariates within a paediatric population, they generally do not account for real-time growth and maturation of the individuals through the time course of drug exposure; this may be significant in prolonged neonatal studies. The major objective of this study was to introduce age progression into a paediatric PBPK model, to allow for continuous updating of anatomical, physiological and biological processes in each individual subject over time. The Simcyp paediatric PBPK model simulator system parameters were reanalysed to assess the impact of re-defining the individual over the study period. A schedule for re-defining parameters within the Simcyp paediatric simulator, for each subject, over a prolonged study period, was devised to allow seamless prediction of pharmacokinetics (PK). The model was applied to predict concentration-time data from multiday studies on sildenafil and phenytoin performed in neonates. Among PBPK system parameters, CYP3A4 abundance was one of the fastest changing covariates and a 1-h re-sampling schedule was needed for babies below age 3.5 days in order to seamlessly predict PK (<5% change in abundance) with subject maturation. The re-sampling frequency decreased as age increased, reaching biweekly by 6 months of age. The PK of both sildenafil and phenytoin were predicted better at the end of a prolonged study period using the time varying vs fixed PBPK models. Paediatric PBPK models which account for time-varying system parameters during prolonged studies may provide more mechanistic PK predictions in neonates and infants.

Impact of antiretroviral therapy interruption on plasma biomarkers of cardiovascular risk and lipids: 144‐week final data from the STOPAR study

The aim of the study was to investigate changes in plasma biomarkers of cardiovascular risk and lipids in a CD4-guided antiretroviral therapy interruption study. This was a substudy of a prospective, randomized, multicentre treatment interruption study. At months 12, 24 and 36, monocyte chemotactic protein-1 (MCP-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), interleukin-6 (IL-6), interleukin-8 (IL-8), soluble CD40 ligand (sCD40L), soluble P-selectin (sP-selectin), and tissue plasminogen activator (t-PA) were measured using a multiplex cytometric bead-based assay. Total cholesterol (total-c), high-density lipoprotein cholesterol (HDL-c) and triglycerides (TG) were determined using standard methods. Fifty-four patients were included in the study [34 in the treatment continuation (TC) arm and 20 in the treatment interruption (TI) arm]. There were no differences at baseline between the groups, except in CD4 cell count, which was higher in the TI arm (P = 0.026), and MCP-1, which was higher in the TC arm (P = 0.039). MCP-1 and sVCAM-1 were increased relative to baseline at the three study time-points in the TI arm, with no changes in the TC arm. Soluble CD40L and sP-selectin were increased at month 36 in both arms, with a greater increase in the TI arm (P = 0.02). t-PA was increased in both arms at the three time-points. Total-c, HDL-c and low-density lipoprotein cholesterol (LDL-c) were decreased in the TI arm at the three time-points, with no changes in the total-c/HDL-c ratio. HIV viral load positively correlated with MCP-1 at months 12 and 24. Regression analysis showed a significant negative association of HDL-c with MCP-1 and sVCAM-1. A significant increase in cardiovascular risk biomarkers persisting over the prolonged study period was seen in the TI arm. This factor may contribute to the increased cardiovascular risk observed in previous studies.

Seasonal and group effects on dairy cow behavior in large yards

In mechanized modern dairy facilities with competitive environments, monitoring behavior provides opportunities to manipulate and optimize the nutritional, health, and social status of high-merit cows. The objective of the current study was to determine seasonal and cow group effects on the eating, ruminating, standing, and lying behaviors of dairy cows in large yards. Seasonal data on various behaviors of lactating cows in different production and lactation stages were collected continuously for 26 months, from December 2006 through February 2008. The herd had approximately 3000 dairy cattle housed in groups within specific yards. A total of 415 multiparous high-producing cows (MH), 166 multiparous medium-producing cows (MM), 166 multiparous low-producing cows (ML), 165 primiparous high-producing cows (PH), 83 fresh cows (FC), 82 fresh heifers (FH), and 82 cows with high milk somatic cell count (HSCC) were monitored. Seasonal eating, ruminating, standing, and lying behaviors were recorded by 4 trained individuals at 1000 hours every week, on 4 days per week. Each activity was expressed as the proportion of cows exhibiting the activity relative to the total number of cows in the yard. Feed was delivered 6 times daily, 4 times as TMR at 0600, 1030, 1300, and 1800, just after milking and twice as alfalfa hay at nighttime. Across all groups, a greater proportion of cows were observed eating during winter (25.7%) than during spring (17.1%), summer (15.4%), and autumn (14.5%). The proportion of cows neither eating nor ruminating was lower in winter (48.1%) than in summer (58.9%) and autumn (58.6%), but similar to spring (53.7%). A greater proportion of cows in the PH (24.6%) and ML (21.3%) groups were observed eating, compared with the MM (15.2%), MH (16.6%), and FC (12.6%) groups. Lying was observed significantly more often in the FC (71%), MM (69.6%), HSCC (65.3%), and MH (64%) groups than in FH (54%), ML (55.7%), and PH (55.7%) groups. A greater proportion of cows were observed ruminating in the MM (31.7%), FC (31.3%), HSCC (28.7%), PH (27.2%), and MH (26.7%) groups, when compared to the FH (20.5%) and ML (22.9%) groups. The HSCC cows were less active in eating and more active in lying than the PH and ML groups. With the remarkably large sample size and prolonged study period, these findings reveal the determining effects of season alongside age, lactation stage, productivity, and-to some extent-mastitis on the eating, ruminating, and resting behaviors of dairy cows in large yard houses.

Real-time electrical measurement of L929 cellular spontaneous and synchronous oscillation.

Nonexcitable cell types, fibroblasts of heart muscle or astrocytes, are well known for their spontaneous Ca2+ oscillations. On the other hand, murine fibroblast (L929) cells are known to be deficient in cell–cell adhesive proteins and therefore lack gap junctions for cellular communication. However, these cells exhibit a unique property of collectively synchronized and spontaneous oscillation, as revealed by real-time monitoring of cells cultured on a 250-μm diameter microelectrode for more than 3 days using an electrical cell-substrate impedance-sensing system (ECIS). Live-cell imaging is a widely used technique for oscillation detection, but it has limitations relating to cellular physiological environment maintenance for microscopic analysis and for prolonged periods of study. The present research emphasizes an electrical-sensing technique (ECIS) capable of overcoming the most important issues inherent in live-cell imaging systems for the detection of L929 cellular spontaneous and synchronized oscillation in real-time for longer periods. Possible mechanisms involved in L929 oscillation were elucidated to be periodic extension/contraction of lamellipodia continued as blebbing, which is produced by signals from the actomyosin complex initiated by connexin hemichannel opening and adenosine triphosphate (ATP) release. By applying the connexin hemichannel inhibitor, flufenamic acid, the hindrance of ATP release and calcium transients were analyzed to elucidate this hypothesis.

Previous injury as a risk factor for injury in elite football: a prospective study over two consecutive seasons

Background: Previous injury is often proposed to be a risk factor for football injury, but most studies rely on players reporting their own medical history and are thus potentially subject...

Epidemic and Endemic Spread of Klebsiella pneumoniae Producing SHV-5 Beta-Lactamase in Dubrava University Hospital, Zagreb, Croatia

Plasmid-encoded resistance to broad-spectrum cephalosporins and aztreonam is becoming a widespread phenomenon in clinical medicine. These antibiotics are inactivated by an array of different extended-spectrum β-lactamases (ESBLs) which have evolved by point mutations of parental TEM or SHV β-lactamases. In a previous study conducted during 1994-1995, SHV-2, SHV-2a and SHV-5 β-lactamases were found among Klebsiella pneumoniae isolates in Dubrava University Hospital. High prevalence of ESBLs among K. pneumoniae strains in this hospital (20%) required further investigation. In this investigation, β-lactamases from 42 K. pneumoniae strains collected in 1997 and 15 in 2004 from Dubrava University Hospital, were characterized in order to study the evolution of plasmid-encoded resistance to extended-spectrum cephalosporins and aztreonam in that hospital over a prolonged study period. Susceptibility to antibiotics was determined by diskdiffusion and broth microdilution method. β-lactamases were characterized by isoelectric focusing, determination of hydrolysis of β-lactam substrates, polymerase chain reaction and sequencing of blaSHV genes. All K. pneumoniae strains and their Escherichia coli transconjugants produced β-lactamase with an isoelectric point of 8.2. Based on sequencing of blaSHV genes enzymes of all transconjugants were identified as SHV-5 β-lactamase which conferred on the producing isolates high level of ceftazidime and aztreonam resistance. In this study, an outbreak of nosocomial infections caused by SHV-5 producing K. pneumoniae was described in 1997 which evolved to endemic spread of SHV-5 producing K. pneumoniae due to multiple plasmid transfer in the Dubrava University Hospital. The strains from 1997 and 2004 were not clonally related. Hospital hygiene measures should be applied in order to control the spread of epidemic strains through the hospital wards and the consumption of the broad-spectrum cephalosporins needs to be restricted to reduce the selection pressure which enables the proliferation of ESBL producers in hospital.

Effect of Oral and Intravenous Insulin and Glutamic Acid Decarboxylase in NOD Mice

Islet cell antigens have been administered orally and intravenously (I.V.) to NOD mice to assess their abilities to protect from or delay the onset of diabetes, and thereby provide insights that may have therapeutic implications in human trials. Whereas we and others have observed a delay in the onset of diabetes in NOD mice that have been fed with insulin from early life, we report here for the first time that feedings with porcine GAD65 alone (p = 0.226) or in combination with insulin (p = 0.011), have anti-diabetic effects in a prolonged study period (>400 days). While antigen-specific inhibitions of in vitro lymphocytic proliferation responses were seen (p < 0.05), antibody levels were unaffected by oral antigen treatments. IFN-γmRNA levels were downregulated in the islet infiltrates following oral antigen treatments while IL-2 and TNF-β were expressed in all instances. We also observed that I.V. human recombinant GADgs, and porcine GAD given at weaning, delayed diabetes onset (p = 0.004) while similar treatments with a variety of inactive insulin preparations were generally ineffective. These findings thus indicate varying effects of oral and I.V. autoantigen administrations on the development of diabetes in NOD mice, and describe the immunological processes induced by oral autoantigen treatments.

A comparison of hypertonic to isotonic fluid in the resuscitation of brain injury and hemorrhagic shock

We studied the early and late effects of hypertonic resuscitation (HR) on the injured brain using a porcine model of hemorrhagic shock and focal cryogenic brain injury. After shock, swine were randomly assigned to receive a bolus (4 cc/kg) of either Ringers lactate (RL) or 7.5% hypertonic saline in 6% Dextran 70, followed by either RL or hypertonic sodium lactate to restore mean arterial pressure to baseline. All animals were studied for 24 hr after the start of resuscitation. Bolus HR improved cerebral blood flow (CBF) with a lower intracranial pressure (ICP) than RL. Continued hypertonic resuscitation prolonged the period of improved CBF and low ICP. At 24 hr CBF had deteriorated in the region of injury in all study groups and in the uninjured hemisphere in swine receiving RL. These data suggest that rapid resuscitation without increasing ICP for up to 6 hr as seen with hypertonic fluid could conceivably allow adequate time for surgical evacuation of mass lesions and effectively prevent secondary brain injury. This work underscores the importance of prolonged periods of study when evaluating brain resuscitation from traumatic shock.