Assessment of lisdexamfetamine on executive function in rats: A translational cognitive research.

Executive function, including working memory, attention and inhibitory control, is crucial for decision making, thinking and planning. Lisdexamfetamine, the prodrug of d-amphetamine, has been approved for treating attention-deficit hyperactivity disorder and binge eating disorder, but whether it improves executive function under non-disease condition, as well as the underlying pharmacokinetic and neurochemical properties, remains unclear. Here, using trial unique non-matching to location task and five-choice serial reaction time task of rats, we found lisdexamfetamine (p.o) enhanced spatial working memory and sustained attention under various cognitive load conditions, while d-amphetamine (i.p) only improved these cognitive performances under certain high cognitive load condition. Additionally, lisdexamfetamine evoked less impulsivity than d-amphetamine, indicating lower adverse effect on inhibitory control. In vivo pharmacokinetics showed lisdexamfetamine produced a relative stable and lasting release of amphetamine base both in plasma and in brain tissue, whereas d-amphetamine injection elicited rapid increase and dramatical decrease in amphetamine base levels. Microdialysis revealed lisdexamfetamine caused lasting release of dopamine within the medial prefrontal cortex (mPFC), whereas d-amphetamine produced rapid increase followed by decline to dopamine level. Moreover, lisdexamfetamine elicited more obvious efflux of noradrenaline than that of d-amphetamine. The distinct neurochemical profiles may be partly attributed to the different action of two drugs to membranous catecholamine transporters level within mPFC, detecting by Western Blotting. Taken together, due to its certain pharmacokinetic and catecholamine releasing profiles, lisdexamfetamine produced better pharmacological action to improving executive function. Our finding provided valuable evidence on the ideal pharmacokinetic and neurochemical characteristics of amphetamine-type psychostimulants in cognition enhancement.

The protective effect of LCZ696 in coxsackievirus B3-induced acute viral myocarditis mice.

AIMS: Acute viral myocarditis (AVMC) is the aetiology of heart failure (HF) with few specific treatments. The improvement of left ventricular ejection fraction (LVEF) is a critical predictor for the prognosis of AVMC. LCZ696 is a drug used in HF to improve LVEF, with a few research on AVMC. In this research, we evaluated the effects and mechanism of LCZ696 in improving LVEF in AVMC. METHODS: Eighty 4-week-old male BALB/c mice were randomly divided into four groups of 20: Sham; Sham + LCZ696 (60 mg/kg/d); AVMC; AVMC + LCZ696. The above experiments were repeated by CVB3-infected HL-1 and Mdivi-1 to down-regulated dynamin-related protein 1(Drp1). Adeno-associated virus 9 (AAV9) with enhanced green fluorescent proteins (GFP) was injected to produce Drp1-overexpression mice and set up four groups: AVMC group, AVMC + AAV group, AVMC + LCZ696 group, and AVMC + LCZ696 + AAV group (n = 20 in each group). LVEF was evaluated by echocardiography at a similar heart rate (HR) at d7, Drp1 (p-Drp1), inflammation and apoptosis by histology and Western blot (WB), and mitochondrial by electron microscopy. RESULTS: Cardiac function were injured in AVMC that LCZ696 reversed (LVEF, %: Sham: 68.99 ± 9.67; Sham + LCZ696: 71.96 ± 6.20; AVMC: 30.95 ± 6.40*; AVMC + LCZ696: 68.99 ± 9.67*#, *P < 0.05 vs. Sham, #P < 0.05 vs. AVMC). LCZ696 attenuated p-Drp1 expression, inflammation, apoptosis, and mitochondrial fission (p-Drp1/Drp1: Sham: 1; Sham + LCZ696: 1.37 ± 0.22; AVMC: 2.29 ± 0.36*; AVMC+LCZ696: 1.43 ± 0.08*#, *P < 0.05 vs. Sham, #P < 0.05 vs. AVMC). Some of the above results were repeated in CVB3-infected HL-1 cells and Mdivi-1. AAV increased Drp1 expression and mitochondrial fission, inflammatory, and apoptosis. Compared with the AVMC + AAV group, the LVEF increased from 24.44 ± 0.03% to 32.33 ± 0.05% in the AVMC + LCZ696 + AAV group(P < 0.05), p-Drp1/Drp1 decreased from 0.54 ± 0.12 to 0.42 ± 0.09*, and IL-6, c-IL-1ß, and c-caspase-3/caspase-3 decreased from 1.07 ± 0.22 to 0.72 ± 0.08*, from 1.03 ± 0.14 to 0.79 ± 0.09*, and from 4.69 ± 0.29 to 0.92 ± 0.13*, respectively (*P < 0.05). CONCLUSIONS: LCZ696 has a protective effect on AVMC by improving LVEF and reducing inflammation and apoptosis, which may be due to the inhibition of Drp1-mediated mitochondrial fission.

Inter-coffee-ring effects boost rapid and highly reliable SERS detection of TPhT on a light-confining structure.

Triphenyltin chloride (TPhT) is a widely applied toxic compound that poses a significant threat to humans and the environment. Surface-enhanced Raman spectroscopy (SERS), capable of non-destructive, rapid, and trace detection, is desirable to better evaluate its distribution and content. However, a sensitive method with simple measuring protocols which maintains excellent reproducibility remains challenging. Here, we proposed an inter-coffee-ring effect to accelerate the sampling and measuring process while maintaining highly reproducible results. Two overlapping coffee-rings are formed through sequenced drying of gold nanorod colloids and a gold nanorod TPhT mixture on a superhydrophobic light-confining structure. Both the gold nanorods and the TPhT are enriched in the overlapping region. The gold nanorods reordered in such an area under the inter-coffee-ring effect yielded vast numbers of consistent hotspots at the sub-2 nm level. Such consistency leads to excellent SERS performance under the light-confining effect induced by the nanoarray substrates. The detection limits of the probe molecule R6G reached 10-12 M, and TPhT reached 10-8 M while achieving excellent stability and reproducibility, and a linear regression coefficient above 0.99 was achieved for TPhT. Crucially, the visible nature of the inter-coffee-ring overlap enabled rapid measurements, thus providing robust support for detecting environmental pollutants.

Comparison of open-skill and closed-skill exercises in improving the response inhibitory ability of the elderly: a protocol for a randomised controlled clinical trial.

INTRODUCTION: As people age, they are more likely to experience a decline in their response inhibition ability, which interferes with daily life. Previous studies have shown that exercise intervention can improve the cognitive ability of the elderly, but research on open-skill and closed-skill exercises to improve the response inhibition in this age group is still limited. This study will explore the advantages of long-term intervention of table tennis (open-skill exercise) compared with fit aerobics (closed-skill exercise) on the response inhibitory ability of the elderly. METHODS AND ANALYSIS: A single-blind randomised controlled trial will be conducted. A total of 90 elderly subjects will be recruited and allocated randomly to the following groups: table tennis, fit aerobics and control. The interventions for the table tennis group and the fit aerobics group will be implemented in three 60 min sessions per week for 6 months; the control group will receive no exercise intervention. The primary assessment will be behavioural indicators of response inhibitory ability in the elderly based on the stop signal task. The secondary outcomes will include cognitive ability, mental status and depression in the elderly. Assessments will be conducted at baseline, 3 months, 6 months and 12 months. ETHICS AND DISSEMINATION: This study was approved by the Shanghai University of Sport Research Ethics Committee (102772019RT012) and will provide reference for the advantages of table tennis compared with other types of sports in improving the response inhibitory ability of the elderly. The results of this study will provide a theoretical basis for choosing the best exercise programme to improve the response inhibitory ability of the elderly. TRIAL REGISTRATION NUMBER: This study has been registered prospectively in the Chinese Clinical Trial Registry (ChiCTR2100043616, 23 February 2021).

Comparison of Ultrasound-Guided Erector Spinae Plane Block and Oblique Subcostal Transverse Abdominis Plane Block for Postoperative Analgesia in Elderly Patients After Laparoscopic Colorectal Surgery: A Prospective Randomized Study.

INTRODUCTION: Postoperative analgesia in elderly patients is still a thorny problem. Ultrasound-guided oblique subcostal transverse abdominis plane block (TAPB) has been demonstrated to provide postoperative analgesia after abdominal surgeries. However, recent studies have suggested that an alternative method, erector spinae plane block (ESPB), might also be effective. In this study, we compared the postoperative analgesic effects of ESPB and TAPB in elderly patients who had undergone laparoscopic colorectal surgery. METHODS: Sixty-two elderly patients (≥ 65 years old) scheduled for elective laparoscopic colorectal surgery with general anesthesia were randomly allocated to two equally sized groups: ESPB group and TAPB group. The ESPB group had a bilateral erector spinae plane block, and the TAPB group had a bilateral oblique subcostal transverse abdominis plane block. The primary outcome was visual analogue scale (VAS) pain score during the first 24 postoperative hours at resting and active states. The secondary outcomes were postoperative consumption of sufentanil, satisfaction score, the number of patients who required antiemetics, incidence of block-related complications, and other side events. RESULTS: There were no demographic differences between two groups. Compared to the TAPB group, the ESPB group had lower VAS pain scores and sufentanil consumption during the first 24 postoperative hours. Additionally, ESPB reduced the occurrence of postoperative nausea and vomiting. Furthermore, the satisfaction score was higher in the ESPB group. No other complications were reported between the two groups. CONCLUSIONS: Compared with oblique subcostal TAPB, ESPB more effectively reduced postoperative pain and opioid consumption. Thus, ESPB is suitable for postoperative analgesia in elderly patients who have undergone laparoscopic colorectal surgery. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR2000033236.

Efficacy and safety of danoprevir plus sofosbuvir in GT 1, 2, 3, or 6 chronic hepatitis C patients with or without cirrhosis in China.

ABSTRACT: All-oral direct-acting antiviral therapies are becoming the choice for hepatitis C (HCV) treatment. In this study, we aimed to evaluate the efficacy and safety of ritonavir-boosted danoprevir (DNVr) plus sofosbuvir±ribavirin on HCV genotype 1, 2, 3, or 6 in the real world in China.In this observational, prospective, multicenter cohort, we enrolled a total of 58 patients with HCV genotype 1, 2, 3, or 6 patients from July 2018 to December 2019. All patients were treated with DNVr plus sofosbuvir ± ribavirin for 12 weeks and then followed up for 12 weeks. The primary endpoint was the rate of sustained virologic response at week 12 after the end of treatment (SVR12). The secondary endpoint was virologic response rate at end-of-treatment and adverse event outcome.Of the 58 patients who were enrolled, 5.2% (n = 3) had genotype 1a; 43.1% (n = 25) had HCV genotype 1b; 17.2% (n = 10) had genotype 2a; 5.2% (n = 3) had genotype 3a; 8.6% (n = 5) had genotype 3b; and 20.7% (n = 12) had genotype 6a. The virologic response rate at end-of-treatment was 100% (58/58). The HCV-RNA results of 5 patients were absent at week 12 after treatment. Among the 53 patients, SVR12 rate achieved 100% (53/53) with DNVr plus sofosbuvir ± ribavirin treatment in patients with HCV genotype 1b, 2a, 3, and 6a. For compensated cirrhosis and noncirrhosis patients, SVR12 was 100% with DNVr plus sofosbuvir ± ribavirin treatment. No serious event was observed during the treatment and follow-up. Only 5 patients had mild adverse events.DNVr plus sofosbuvir ± ribavirin for 12 weeks provided 100% SVR12 in a broad patient population and were well tolerated, which may be a promising regimen for CHC treatment.

The effects of rhBMP-2 and Treg/Th17 functional disequilibrium in uremic patients with cardiovascular complication after maintenance hemodialysis.

OBJECTIVES: We compared the correlation of regulatory T cell (Treg) and Th17 cell function disequilibrium with calcification in uremic patients on maintenance hemodialysis (MHD) with healthy controls, and investigated if their influence possibly increased the development and outcome of cardiovascular complications in uremic patients after MHD. METHODS: The extent of coronary artery calcification was assessed by coronary artery calcification scoring (CACS) in uremic patients with and without adverse cardiovascular events after MHD (MHD group 1 vs. MHD group 2, respectively). Peripheral blood mononuclear cells were incubated with rhBMP-2 as positive control. The Treg/Th17 cell frequencies, Foxp3 ROR-gt mRNA expressions, and MIP 3α/CCL20 concentrations were measured. RESULTS: The CACS score was significantly higher in MHD group 1 as compared group 2. In comparison with controls, rhBMP-2 upregulates Treg/Th17 functional disequilibrium in uremic patients, displayed higher Treg and Th17 frequencies, Foxp3 and ROR-gt expressions, and MIP3α/CCL20 concentrations. However, the up-regulations of Treg frequencies and Foxp3 expressions were significant in controls but not in MHD patients. It was also observed that Treg/Th17 functional disequilibrium was not only correlated with rhBMP-2 state but also consistent with the cardiovascular complications. Moreover, the CACS was negatively correlated with Treg cell frequencies but positively correlated with Th17 cell frequencies and MIP3a/CCL20 concentrations. CONCLUSIONS: Function disequilibrium of Treg/Th17 was related to the degree of the rhBMP-2 state. Function disequilibrium of the Treg/Th17 might act synergistically with rhBMP-2 in the high incidence of immune-mediated cardiovascular complications after MHD.

[A comparison between clinical value of the liver transplantation standard mathematical model score and Child-Turcotte-Pugh score in evaluating the prognosis of liver failure].

OBJECTIVE: To compare the clinical value of the liver transplantation standard (LTS) mathematical model score and Child-Turcotte-Pugh (CTP) score in evaluating the prognosis of liver failure. METHODS: The clinical data of 150 liver failure patients were analyzed retrospectively. All the patients who were admitted from January 2004 to December 2008 were divided into survival group (n=48) and death group (n=102) in regard to their 90-day survival after their admission. LTS score and CTP score were calculated according to their respective clinical data within 24 hours after their admission. Comparison between LTS score and CTP score was conducted respectively between the survival group and death group. The correlation between LTS score/CTP score and the prognosis of liver failure was made by Spearman rank correlation. The ability of LTS score and CTP score to predict the outcome of liver failure was compared with the receiver operating characteristic (ROC) curve. RESULTS: The LTS score and CTP score of survival group were 38.88+/-4.27 and 11.25+/-0.97, respectively, which were lower than those of death group (52.63+/-10.65 and 12.18+/-1.22, both P<0.01). The correlation coefficient of LTS score and the prognosis of liver failure (r(s)=0.651, P<0.01) was higher than that of CTP score (r(s)=0.366, P<0.01). The area under ROC curve (AUC) of LTS score was 0.897, sensitivity (SN) was 76.52%, specificity (SP) was 91.18%, positive predictive value (PV+) was 94.39%, negative predictive value (PV-) was 66.67%, and Youden index was 0.677, respectively. The AUC of CTP score was 0.716, those of SN, SP, PV+, PV- and Youden index were 40.91%, 92.65%, 91.53%, 44.68% and 0.336, respectively. CONCLUSION: The LTS score is better than the CTP score in evaluating the prognosis of liver failure.

A pattern of otoferlin expression interrupted by gentamicin exposure in ribbon synapse of inner hair cell in C57BL/6J mice.

Despite ototoxic effect of aminoglycosides on auditory sensory system has been well documented, the mechanism of ototoxic damage on synaptic connection (ribbon synapse) between inner hair cells (IHCs) and spiral ganglion neurons (SGNs) is still largely unknown. Otoferlin is essential for a late step in exocytosis of neurotransmitter at ribbon synapses. In this study, C57BL/6J mice were intraperitoneally injected with gentamicin (100 mg/kg) once a day, the apical coils of organ of Corti were obtained at the 4th day, the 7th day and the 10th day respectively (n = 10/per group), the normal mice without a Gentamicin exposure were set for control (n = 10/per group). Otoferlin was detected by both immunofluorescence and western blotting. The hearing thresholds were measured by auditory brainstem responses (ABR). The expression of Otoferlin was up-regulated during the period of first 7days with a Gentamicin exposure. The down-regulation of Otoferlin expression was found after the 7th day with a gentamicin exposure. The hearing thresholds showed a linear increase. Gentamicin exposure may enhance transiently the expression of Otoferlin in ribbon synapse in C57BL/6J mice. This property might correlate with the ribbon synaptic plasticity in C57BL/6J mice. It may provide us a new insight for a further detailed study of the ribbon synaptic plasticity under the condition of aminoglycosides application.

[Genetic diversity of duck breeds: a study with microsatellite markers].

Thirty two microsatellite markers were utilized to analyze the genetic diversity and germplasm characteristics of five Fujian native duck breeds (Jinding duck, Liancheng white duck, Putian black duck, Shanma duck, and Muscovy duck) and two reference duck breeds (Beijing duck and Khaki Campbell duck). By using the markers, 371 alleles in test duck breeds were detected. The average allelic number per locus was 11.719, average value of PIC was 0.522, average number of effective alleles was from 5.141 to 6.961, and average heterozygosity was from 0.512 to 0.700. Based on Nei's standard distance (D(S)) and DA genetic distance, a dendrogram was constructed by using the unweighted pair group method with arithmetic mean (UPGMA). Jinding duck, Putian black duck, Liancheng white duck, Shanma duck, and Khaki Campbell duck were clustered into a group, and Beijing duck and Muscovy duck were clustered into another two groups, respectively. The dendrogram of D(A) and D(S) genetic distances were accorded with the real relations among the seven duck breeds.

[The effect and pathophysiological mechanism of high free fatty acids(FfAs) on the cardiac structure and function].

OBJECTIVE: To study the pathophysiological links between elevated circulating FFAs concentration and the cardiac structure, and their function in obese insulin resistance rat model. METHODS: 4 weeks age male SD rats were fed with high-fat chow (OB) or standard laboratory chow (NC) respectively. Whole-body insulin sensitivity, the maximum velocity of myocardial contraction (+dp/dt(max)) and the maximum velocity of myocardial diastole (-dp/dt(max)) of intracardiac pressure, and myocardiac cell diameter (MCD) were measured. The concentrations of triglyceride (TG), FFAs and angiotensin II (Ang II) both in blood and in left ventricular portions of heart and the expressions of NF-kappaB, I-kappaB and iNOS in myocardium were analyzed. RESULTS: OB group developed obesity and left ventricular hypertrophy, and their insulin sensitivity was much lower than that of control group. Obese rats had higher plasma concentrations of TG, FFAs and Ang II. Accordingly, dramatic lipid deposition occurred within cardiomyocytes of obese rats, and the value of myocardiac Ang II was also increased. High-fat diet also induced a progressive decrease in values of +dp/dt(max) and -dp/dt(max). The higher expressions of NF-kappaB and iNOS in myocardium were observed in OB group, while IkappaB lower. Intramyocardial lipid deposition was associated with plasma FFAs concentrations (r = 0.80, P < 0.01). Intramyocardial FFAs concentration was associated with myocardial Ang II concentration (r = 0.74, P < 0.05) and changes in expressions of NF-kappaB (r = 0.86, P < 0.01), iNOS (r = 0.66, P < 0.05). The contractile dysfunction was associated with intramyocardial lipid deposition (r = -0.87, P < 0.01), Ang II (r = -0.52, P < 0.05) and expressions of NF-kappaB (r = -0.57, P < 0. 01), iNOS (r = -0.70, P < 0. 01). The diastolic dysfunction was associated with intramyocardial lipid deposition ( r = -0.85, P < 0.01), Ang II (r = -0.82, P<0.01) and expressions of NF-kappaB (r = -0.75, P < 0.01), iNOS (r = -0.78, P < 0.01). CONCLUSION: In obese/insulin resistance, state ectopic lipid accumulation in myocardium as the results of elevated circulating FFAs and TG concentration impairs cardiac systolic and diastolic functions. It is logical to deduce that ectopic lipid accumulation in myocardium may increase RAS activity and expressions of NF-kappaB, iNOS in myocardium, all of them have important roles to increase the risk of congestive heart failure in obese subjects.

Space-occupying lesions in Papua New Guinea--the CT era.

BACKGROUND: The use of computed tomography (CT) scanning to diagnose and treat space-occupying lesions (SOL) has been a great advance. AIM: To analyze the causes, treatment and outcome of SOL. METHOD/PATIENTS: An audit of all cases of SOL treated over a period of 2 years (2003-2004) after the establishment of a neurosurgical unit. RESULTS: There were 42 SOL cases affecting the intracranial space and the spine. 39 cases originated in the brain and its coverings and 3 in the spinal cord. Out of the 39 brain SOL, 26 (67%) were due to tumours and 13 (33%) were due to infection, of which tuberculosis was responsible for 6 (46%). There were 6 astrocytomas and 3 meningiomas followed by secondaries, pilocytic astrocytoma and medulloblastoma with 2 cases each. There was also one case each of pineal tumour, craniopharyngioma, pituitary adenoma, vestibular schwannoma and oligodendroglioma and 6 indeterminate cases. The 3 spinal cord SOL were due to arachnoiditis, subdural abscess and tuberculoma. CONCLUSION: Tumours were more common than tuberculosis as a cause of SOL. However, tuberculoma represented a curable condition whereas for tumours the potential for cure depended on the site, pathology and stage. CT scan was of great help in the diagnosis and localization of SOL but, unfortunately,is still not available for the majority of the Papua New Guinea population.

Open depressed and penetrating skull fractures in Port Moresby General Hospital from 2003 to 2005.

BACKGROUND: Open wounds to the head with skull bone depression pose the potential for serious injuries to the brain parenchyma and an increased risk of infection. The treatment of these injuries aims to repair the breached dura as well as remove any nidus for infection. Open wounds to the head due to bullets pose special problems and have a high fatality rate. AIM: To review the presentation, management and outcome of depressed and penetrating open fractures of the skull in Port Moresby. METHOD: All cases seen from 2003 to 2005 were included. All were managed without a CT (computed tomography) scan. Their Glasgow Outcome Scale (GOS) was documented on discharge. RESULTS: There were 340 traumatic brain injury (TBI) cases over a period of 3 years between 2003 and 2005 managed by the Neurosurgery Unit of Port Moresby General Hospital. The open depressed and penetrating skull fractures seen in these cases numbered 46 (14%), of which 42 were males and 4 females. The weapons most commonly used were blunt objects (16), knives (11), guns (6) and axes (4). Gunshots contributed to 4 of the 7 deaths. 4 out of the 7 deaths were due to primary brain injury and 3 were due to infection. CONCLUSION: Open depressed fractures and penetrating injuries form a small but significant group in the management of head injuries. The use of blunt objects, firearms and arrows coupled with increasing urban violence is responsible for most of these injuries. The outcome of patients admitted who are fully conscious is expected to be good. They can be managed by prompt debridement of the wound, elevation of the fracture and removal of fragments as appropriate. However, the mortality rate is high in those with a Glasgow Coma Score of 8 or less on admission, a finding indicative of the severity of brain injury beneath the wound.

Big heads in Port Moresby General Hospital: an audit of hydrocephalus cases seen from 2003 to 2004.

BACKGROUND: Hydrocephalus is a common neurosurgical problem in Port Moresby General Hospital (PMGH) contributing to 27 (24%) of the 114 neurosurgical operations done in 2003 and 2004. During the same period it was responsible for 25% of the cases seen in the neurosurgery clinic. AIM: To prospectively audit and follow up hydrocephalus cases in PMGH over 2 years from January 2003 to December 2004 and ascertain the causes and the outcome of treatment. METHOD: All cases of hydrocephalus seen in 2003 and 2004 were categorized according to cause. The associated findings on ultrasound scan or CT (computed tomography) scan when available were noted. The subsequent progress was documented with and without treatment for at least 6 months. RESULTS: 61 cases of hydrocephalus were seen for surgical opinion. The age ranged from 4 weeks to 56 years. The commonest age group affected was in the first year of life (61% of cases). There were 34 cases (56%) of congenital hydrocephalus followed by 19 (31%) post meningitis and 8 (13%) due to tumour. There was only one case of myelomeningocele with concomitant hydrocephalus. Ventriculoperitoneal (VP) shunts were inserted in 24 cases. 3 shunts were bypasses from the posterior horn to the cisterna magna, making a total of 27 shunt operations. 9 shunts were performed for post-meningitic hydrocephalus, 15 for congenital stenosis and 3 for a posterior fossa tumour. 24 out of the 27 shunt operations were in children aged <9 months. Post-VP-shunt infection of 2 cases reported within 6 weeks of operation gave an infection rate of 7%. There was cerebrospinal fluid (CSF) leak in 2 cases with Pundez-type shunts. There were 2 shunt blocks needing revision. CONCLUSION: Shunt operations can be done in PMGH with good outcomes. The decision-making about surgery can be made on the basis of the enlarging head and the ultrasound findings.

Trends in traumatic brain injury outcomes in Port Moresby General Hospital from January 2003 to December 2004.

BACKGROUND: Traumatic brain injury (TBI) has been responsible for 25-30% of surgical deaths in Port Moresby General Hospital (PMGH) over the last 30 years despite being responsible for only 5% of the admissions. AIM: To document the epidemiology of TBI over a period of two years from 2003 to 2004 and compare this to the previous two decades in PMGH and elsewhere. The treatment and outcome of TBI cases are analyzed. METHODS: All TBI cases were included from January 2003 to December 2004. The Glasgow Coma Score (GCS) and Glasgow Outcome Scale (GOS) were documented at admission and discharge. These cases were followed up in the outpatient department for at least 6 months. RESULTS: There were 262 cases of TBI admitted between January 2003 and December 2004. There were 31 deaths during this period. 28 deaths were in the severe TBI category (GCS 3-8) and 3 in the moderate category (GCS 9-12). CONCLUSION: The case fatality rate of severe TBI has been reduced from 60% to just below 30% over the period of 2 years. The formation of a single unit managing TBI over two years may be one factor contributing to this improvement. Interpersonal violence has replaced motor vehicle accidents as the leading cause of death from TBI.

[A study on the mechanism of islet cell insulin resistance in high-fat-diet obese rats].

OBJECTIVE: To study the changes of insulin signal transduction in islet cells of high-fat-diet rats with peripheral insulin resistance (IR). METHODS: Thirty male Wistar rats were randomly divided into 2 equal groups: high-fat-diet group and control group to be fed with high-fat food and normal food respectively. Twenty weeks after the rats were sacrificed. The contents of insulin and glucagon in homogenate of pancreas were detected during islet cell perifusion, and insulin receptor (IRc) and insulin receptor substrates (IRS-1 and IRS-2) were detected by immunohistochemistry. RESULTS: (1) The insulin sensitive index (ISI) was significantly decreased in the high-fat-diet rats in comparison with the normal rats, while the contents of glucagon in blood and in homogenate of pancreas were both significantly increased in the high-fat-diet rats (362 pg/ml +/- 58 pg/ml vs 291 pg/ml +/- 35 pg/ml; 442 pg/ml +/- 56 pg/ml vs 287 pg/ml +/- 48 pg/ml, both P < 0.05). (2) The glucose stimulated insulin secretion (GSIS) was impaired in the high-fat-diet rats. 16.7 nmol/L glucose could inhibit the glucagon secretion by the alpha cells of the normal rats, but not of the high-fat-diet rats. (3) The expression of IRc, IRS-1 and IRS-2 in islets was stronger in the peripheral cells (non-insulin secretion cells) than in the center cells (insulin secretion cells). The expression of IRc and IRS-2 was significantly decreased by 28% and 22% respectively in the high-fat-diet rats compared with the normal controls (both P < 0.01). CONCLUSION: High-fat-diet rats have impairment of insulin signal transduction in islet cells, which may contribute to the insulin resistance of islet alpha and beta cells and explain, at least in part, the dysfunction of the islet cells under peripheral IR.