[Epidemic trends and predictive analysis of other infectious diarrhea in Jiangxi Province, 2017-2022].

Objective: To analyze epidemic trends of other infectious diarrhea in Jiangxi Province from 2017 to 2022, and explore the application of autoregressive integrated moving average (ARIMA) model in the prediction of the incidence of other infectious diarrhea in Jiangxi Province, providing reference for the prediction and prevention and control of other infectious diarrhea. Methods: To conduct a descriptive epidemiological analysis of other infectious diarrhea cases in Jiangxi Province from 2017 to 2022, and establish an ARIMA model to predict the number of other infectious diarrhea cases in 2023. Results: From 2017 to 2022, Jiangxi Province reported 204 842 cases of other infectious diarrhea. The annual average reported incidence rate was 74.32/100 000. The cases were reported in each age group with obvious seasonal characteristics of the main peak. There were two peak periods of incidence in winter and spring (from January to March) and in summer and autumn (from July to September) and the peak value was higher in winter and spring. All parameters of the model ARIMA (0,1,2)(2,1,0)12 and ARIMA (1,0,0)(2,1,0)12 were statistically significant (P<0.05), and the minimum values of Bayesian information criterion were 13.83 and 9.12, respectively. The residual series were all white noise (P>0.05); The predicted value of the model is in good agreement with the actual value, and the predicted trend is consistent with the actual trend. The model has a good prediction effect. Conclusions: The other infectious diarrhea occurred in 2017-2022 was still the first case of notifiable disease in Jiangxi Province. The prevention and control situation cannot be ignored. Disease monitoring and health education for families of children under 3 years of age and scattered children among key populations for prevention and control should be strengthened during the epidemic season. The ARIMA model can be used for short-term prediction and trend analysis of other infectious diarrhea outbreaks in Jiangxi Province.

[Clinicopathological festures and outcome of combined hepatocellular-cholangiocarcinoma].

Objective: To investigate the clinicopathological features and pathological types and outcome of combined hepatocellular-cholangiocarcinoma (cHCC-CC). Methods: 30 cases of cHCC-CC were collected from Jan 2007 to Jun 2021 at General Hospital of Southern Theatre Command, People's Liberation Army of China, and analyzed the clinicopathological features, immunohistochemistry and outcome. The histological morphology was classified according to the Goodman standard and the fifth edition of World Health Organization (WHO) classification of digestive system tumors. Results: According to the Goodman classification, 9 cases belonged to type Ⅰ (i.e., collision tumor), with a coincidental occurrence of hepatocellular carcinoma and cholangiocarcinoma in the same specimen, and 21 cases were Type Ⅱ or "transitional tumors", in which there were areas of intermediate differentiation and an identifiable transition between hepatocellular carcinoma and cholangiocarcinoma. According to the WHO classification of digestive system tumors (5th Edition), 25 cases were classified in cHCC-CC, and 5 cases were cHCC-CC-Intermediate cell carcinoma. There were 28 males and 2 females, with an average age of 50.4 (31-72) years old. 21 cases accompanied liver cirrhosis, with liver flukes in 1 case and HBsAg positive in 23 cases. Immunohistochemical staining showed nestin was positive in 9 cases, 66.7% died (6/9) and 33.3% (3/9) survived only 6 months. The 1-year recurrence rate was 3.9% for liver resection and 50% for orthotopic liver transplantation, and liver resection has longer median survival time than liver transplantation after recurrence. Conclusions: cHCC-CC is a rare type of primary liver malignant tumor. Preoperative diagnosis is difficult. The definite diagnosis depends on histopathological morphology and immunohistochemical markers. Nestin may be as a prognosis factor, and surgical treatment is preferably liver resection.

[Characteristics on molecular epidemiology of Brucella melitensis in Jiangxi province].

Objective: To understand the molecular characteristics and correlation among isolated strains of Brucella melitensis (BM) so as to improve the strategies on prevention and control of the disease in Jiangxi province. Methods: A total of 25 strains of BM isolated from human in 17 counties of Jiangxi province were analyzed by multiple locus variable-number tandem repeat analysis (MLVA) method. Results: A total of 25 strains of BM were classified into 24 independent genotypes with similarities between 67.00% and 100.00% and Simpson index between 0.000 and 0.773. There were 3 genotypes in MLVA8, including 60.00% (15/25) as 42 genotype, 32.00% (8/25) as 43 genotype, and 8.00% (2/25) as 63 genotype, respectively. There were 7 genotypes in MLVA11 identified, with 116 genotype and 125 genotype the main genotypes, accounting for 56.00% (14/25) of all the identified strains. Conclusions: Genes from all the 25 strains of BM that isolated from human being were with high genetic diversities, and various, genotypes. However, no obvious epidemiological correlation was noticed among these strains, indicating the complexity of the source of infection on Brucella in Jiangxi province.

LncRNA GAPLINC promotes the growth and metastasis of glioblastoma by sponging miR-331-3p.

OBJECTIVE: Recent evidence shows that gastric adenocarcinoma predictive long intergenic noncoding RNA (GAPLINC) acts as a critical role in the proliferation and metastasis in several tumors. We aimed to explore the expression pattern, function, and potential mechanism of GAPLINC in glioblastoma multiforme (GBM). PATIENTS AND METHODS: The expression levels of GAPLINC and its clinical significance were determined by analyzing TCGA datasets. RT-PCR was performed to detect the levels of GAPLINC and miR-331-3p. CCK-8, colony formation, EdU assays, wound healing assay and transwell invasion assay were performed to analyze the effect of GAPLINC on GBM behaviors. MiRNAs that may interact with GAPLINC were predicted using StarBase and RegRNA 2.0. A luciferase reporter assay was used to detect the targeting effect of GAPLINC on miR-331-3p. RESULTS: We found that GAPLINC expression was significantly up-regulated in both GBM tissues and cell lines. The overexpression of GAPLINC was associated with shorter overall survival and disease-free survival. Functional assays indicated that GAPLINC silencing suppressed GBM cells proliferation, migration, and invasion, and promoted apoptosis. In the mechanism, we found that GAPLINC acted as a competing endogenous RNA to sponge miR-331-3p and knockdown of GAPLINC promoted the expression of miR-331-3p. CONCLUSIONS: Our findings suggested that GAPLINC served as an oncogenic lncRNA in GBM through negative modulation of miR-331-3p, providing a novel treatment targeting for GBM.

Extended genotypic evaluation and comparison of twenty-two cases of lethal EEHV1 hemorrhagic disease in wild and captive Asian elephants in India.

Thirteen new lethal cases of acute hemorrhagic disease (HD) with typical histopathogical features were identified in young Asian elephants (Elephas maximus indicus) in India between 2013 and 2017. Eight occurred amongst free-ranging wild herds, with three more in camp-raised orphans and two in captive-born calves. All were confirmed to have high levels of Elephant Endotheliotropic Herpesvirus type 1A (EEHV1A) DNA detected within gross pathological lesions from necropsy tissue by multi-locus PCR DNA sequencing. The strains involved were all significantly different from one another and from nine previously described cases from Southern India (which included one example of EEHV1B). Overall, eight selected dispersed PCR loci totaling up to 6.1-kb in size were analyzed for most of the 22 cases, with extensive subtype clustering data being obtained at four hypervariable gene loci. In addition to the previously identified U48(gH-TK) and U51(vGPCR1) gene loci, these included two newly identified E5(vGPCR5) and E54(vOX2-1) loci mapping far outside of the classic EEHV1A versus EEHV1B subtype chimeric domains and towards the novel end segments of the genome that had not been evaluated previously. The high levels of genetic divergence and mosaic scrambling observed between adjacent loci match closely to the overall range of divergence found within 45 analyzed North American and European cases, but include some common relatively unique polymorphic features and preferred subtypes that appear to distinguish most but not all Indian strains from both those in Thailand and those outside range countries. Furthermore, more than half of the Indian cases studied here involved calves living within wild herds, whereas nearly all other cases identified in Asia so far represent rescued camp orphans or captive-born calves.

Analysis of rare periparotid recurrence after parotid gland-sparing intensity-modulated radiotherapy for nasopharyngeal carcinoma.

PURPOSE: Periparotid recurrence is an uncommon phenomenon after intensity-modulated radiotherapy (IMRT) for nasopharyngeal carcinoma. This study aimed to discuss the clinical characteristics, reasonable causes and feasible therapeutic modalities of patients with nasopharyngeal carcinoma and periparotid recurrence. PATIENTS AND METHODS: The medical records of 1852 patients with non-metastatic nasopharyngeal carcinoma treated with initial IMRT between January 2008 and December 2012 were retrospectively reviewed, and nine patients were finally found to have developed periparotid recurrence after IMRT. After periparotid failure, four received radiotherapy and chemotherapy, two had surgery, two had surgery and adjuvant radiotherapy or chemotherapy, and one received radiotherapy alone. RESULT: The incidence rate of periparotid recurrence was 4.9‰. According to pretreatment magnetic resonance imaging (MRI) scans, all patients had both ipsilateral retropharyngeal lymph nodes metastasis with 66.7% of extracapsular spread and level II lymphadenopathy with all extracapsular spread. The median time interval to periparotid failure was 14.8 months, and six patients were found to have a relapse in the primary sites of unsuspicious parotid nodules. After a median follow-up of 46.4 months, five patients developed distant metastasis, three of them developed local failure. In addition, one developed regional failure, one developed locoregional recurrence, and only one was alive without evidence of disease at the last follow-up. CONCLUSION: Periparotid recurrences are rare after definitive IMRT for nasopharyngeal carcinoma. However, patients with ipsilateral retropharyngeal lymph nodes or level II nodal extracapsular spread on pretreatment MRI could be suspicious of metastatic periparotid nodules. Distant metastases were the main treatment failure despite a combination of several salvage treatment of periparotid recurrence. More effective chemotherapy should be explored.

Decrease of microscopic Plasmodium falciparum infection prevalence during pregnancy following IPTp-SP implementation in urban cities of Gabon.

BACKGROUND: Six years after the implementation of intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) in Gabon, its impact on placental malaria and pregnancy outcomes remains unknown. METHODS: Age, gestational data, use of IPTp-SP and birth weight were recorded during a hospital-based cross-sectional survey performed in 2011 in 387 women at the end of pregnancy. RESULTS: Malaria prevalence was 6.7 and 5.3% in peripheral and placental blood respectively. Overall, 59.0% women took at least two IPTp-SP doses which was associated with 50% reduction of Plasmodium; (P.) falciparum infection in primigravidae. Previous malaria treatment was a risk factor for peripheral P. falciparum infection, while uptake of IPTp-SP was associated with reduced parasitaemia. Anaemia prevalence was 38.0%, low birth weight and prematurity rates were 6.0 and 12.0% respectively. Young age was associated with a higher frequency of malaria, anaemia, low birth weight and preterm delivery (p<0.01). Birth weight significantly rose with increasing age (p<0.01), parity (p=0.03) and number of SP doses (p=0.03). A birth weight reduction of 230 g in case of peripheral parasitaemia (p=0.02) and of 210 g with placental parasitaemia (p=0.13) was observed. CONCLUSIONS: Microscopic P. falciparum prevalence during pregnancy significantly declined between 2005 and 2011, following IPTp-SP implementation in Gabon. Young women and paucigravidae remain the most susceptible to malaria and associated outcomes.

Safety, pharmacokinetics, and pharmacodynamics of avoralstat, an oral plasma kallikrein inhibitor: phase 1 study.

BACKGROUND: Avoralstat is a potent small-molecule oral plasma kallikrein inhibitor under development for treatment of hereditary angioedema (HAE). This first-in-human study evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of avoralstat. METHODS: This double-blind, placebo-controlled, ascending-dose cohort trial evaluated avoralstat single doses of 50, 125, 250, 500, and 1000 mg and multiple doses up to 2400 mg daily (100, 200, 400, and 800 mg every 8 h [q8 h] up to 7 days). RESULTS: Avoralstat (n = 71) was generally well tolerated with no signals for a safety concern; there were no serious adverse events (AEs) or discontinuations due to AEs, and compared to placebo (n = 18), no notable difference in AEs. Four moderate severity AEs were reported in two subjects; syncope after a single 250 mg dose (one subject) and abdominal pain, back pain, and eczema after multiple doses of 800 mg avoralstat (one subject). For multiple-dose cohorts, the incidence of gastrointestinal AEs was highest at the 2400 mg/day dose. Elimination of avoralstat was bi-exponential with a terminal half-life of 12-31 h. Inhibition of plasma kallikrein was observed at all doses, and the degree of inhibition was highly correlated with avoralstat concentrations (R = 0.93). Mean avoralstat concentrations at doses ≥400 mg q8 h met or exceeded plasma kallikrein EC50 values throughout the dosing interval. CONCLUSION: Avoralstat was well tolerated, and drug exposure was sufficient to meet target levels for inhibition of plasma kallikrein. Based on these results, the 400 mg q8 h dose was selected for further evaluation in patients with HAE.

Effects of intravenous analgesia with combined dezocine and butorphanol on postoperative cognitive function in elderly patients.

The aim of this study was to observe the analgesic effects of the combination of dezocine and butorphanol on postoperative cognitive function in elderly patients. Forty elderly patients undergoing upper abdominal surgeries or thoracotomies with general anesthesia were randomly divided into the dezocine and butorphanol group or the butorphanol group (20 patients per group). A visual analog scale was used to evaluate analgesia and the degree of malignant vomiting. The Ramsay scoring method was used to evaluate sedation. The Mini-Mental State Examination (MMSE) was used to evaluate cognitive function. Forty-eight hours after the operation, the pain score of the dezocine and butorphanol group (means ± SD, 1.75 ± 0.44) was lower than that of the butorphanol group (2.25 ± 0.79; P < 0.05), and the nausea and vomiting score of the dezocine and butorphanol group (0) was lower than that of the butorphanol group (0.70 ± 1.30; P < 0.05). Six hours after the operation, the sedative score of the butorphanol group (3.75 ± 0.79) was higher than that of the dezocine and butorphanol group (2.15 ± 0.75; P < 0.05). Compared to 1 day before the operation, the MMSE scores of both groups decreased 6 h after the operation, and the MMSE score of the butorphanol group (15.00 ± 2.00) was lower than that of the dezocine and butorphanol group (20.95 ± 1.54; P < 0.05). Dezocine and butorphanol analgesia had transient effects on postoperative cognitive function in elderly patients, and the effect of the combination was superior than butorphanol only.

Sulforaphane protects H9c2 cardiomyocytes from angiotensin II-induced hypertrophy.

BACKGROUND: Cardiac hypertrophy is an adaptive process of the heart in response to various stimuli, but sustained cardiac hypertrophy will finally lead to heart failure. Sulforaphane-extracted from cruciferous vegetables of the genus Brassica such as broccoli, brussels sprouts, and cabbage-has been evaluated for its anticarcinogenic and antioxidant effects. AIMS: To investigate the effect of sulforaphane on angiotensin II (Ang II)-induced cardiac hypertrophy in vitro. METHODS: Embryonic rat heart-derived H9c2 cells were co-incubated with sulforaphane and Ang II. The cell surface area and mRNA levels of hypertrophic markers were measured to clarify the effect of sulforaphane on cardiac hypertrophy. The underlying mechanism was further investigated by detecting the activation of Akt and NF-κB signaling pathways. RESULTS: We found that H9c2 cells pretreated with sulforaphane were protected from Ang II-induced hypertrophy. The increasing mRNA levels of ANP, BNP, and ß-MHC in Ang II-stimulated cells were also down-regulated after sulforaphane treatment. Moreover, sulforaphane repressed the Ang II-induced phosphorylation of Akt, GSK3ß, mTOR, eIF4e, as well as of IκBα and NF-κB. CONCLUSION: Based on our results, sulforaphane attenuates Ang II-induced hypertrophy of H9c2 cardiomyocytes mediated by the inhibition of intracellular signaling pathways including Akt and NF-κB.

Clinico-pathologic features of fatal disease attributed to new variants of endotheliotropic herpesviruses in two Asian elephants (Elephas maximus).

The first herpesviruses described in association with serious elephant disease were referred to as endotheliotropic herpesviruses (EEHV) because of their ability to infect capillary endothelial cells and cause potentially fatal disease. Two related viruses, EEHV1 and EEHV2, have been described based on genetic composition. This report describes the similarities and differences in clinicopathologic features of 2 cases of fatal endotheliotropic herpesvirus infections in Asian elephants caused by a previously unrecognized virus within the betaherpesvirus subfamily. EEHV3 is markedly divergent from the 2 previously studied fatal probosciviruses, based on polymerase chain reaction sequence analysis of 2 segments of the viral genome. In addition to ascites, widespread visceral edema, petechiae, and capillary damage previously reported, important findings with EEHV3 infection were the presence of grossly visible renal medullary hemorrhage, a tropism for larger veins and arteries in various tissues, relatively high density of renal herpetic inclusions, and involvement of the retinal vessels. These findings indicate a less selective organ tropism, and this may confer a higher degree of virulence for EEHV3.

Pharmacokinetics of emtricitabine/tenofovir disoproxil fumarate and tacrolimus at steady state when administered alone or in combination.

OBJECTIVE: An open-label, randomized, 3-way crossover, drug-drug interaction study of the investigational anti-HBV combination agent, emtricitabine/tenofovir DF and the antirejection agent, tacrolimus was conducted in healthy volunteers to evaluate the potential for a pharmacokinetic interaction between these drugs. METHODS: Subjects received emtricitabine/tenofovir DF (200/300 mg q.d.) and tacrolimus (0.1 mg/kg/day) alone or in combination for 7 days, with a 2-week washout between successive treatments. Drug concentrations were measured by LC/MS/MS and steady state pharmacokinetic parameters were calculated for each drug using noncompartmental methods. RESULTS: The 90% confidence intervals (CIs) of the geometric least-squares mean ratio for AUCtau, Cmax and Ctau for each drug together vs. alone were within the predetermined no-effect boundaries of 80 - 125% (representing a maximum 20% effect), other than the upper limit of the 90% CI for tenofovir Cmax, which was just outside the 125% threshold. CONCLUSIONS: It was concluded that there was no clinically relevant pharmacokinetic interaction between emtricitabine/tenofovir DF and tacrolimus when administered together.

Modern evolutionary history of the human KSHV genome.

The genomes of several human herpesviruses, including Kaposi sarcoma (KS) herpesvirus (KSHV), display surprisingly high levels of both genetic diversity and clustered subtyping at certain loci. We have been interested in understanding this phenomenon with the hope that it might be a useful diagnostic tool for viral epidemiology, and that it might provide some insights about how these large viral genomes evolve over a relatively short timescale. To do so, we have carried out extensive PCR DNA sequence analysis across the genomes of 200 distinct KSHV samples collected from KS patients around the world. Here we review and summarize current understanding of the origins of KSHV variability, the spread of KSHV and its human hosts out of Africa, the existence of chimeric genomes, and the concept that different segments of the genome have had different evolutionary histories.

Physical aspects of yttrium-90 microsphere therapy for nonresectable hepatic tumors.

Administration of yttrium-90 microspheres via the hepatic artery is an attractive approach to selectively deliver therapeutic doses of radiation to liver malignancies. This procedure allows delivering radiation absorbed doses in excess of 100 Gy to the tumors without significant liver toxicity. The microsphere therapy involves different specialties including medical oncology, radiation oncology, nuclear medicine, interventional radiology, medical physics, and radiation safety. We have treated 80 patients with nonresectable hepatic tumors with yttrium-90 microspheres during the past two years on an institutional study protocol. The nominal radiation absorbed dose to the tumor in this study was 150 Gy. Required activity was calculated based on the nominal radiation absorbed dose and patient's liver volume obtained from the CT scan, assuming a uniform distribution of the microspheres within the liver. Microspheres were administered via a catheter placed into the hepatic artery. The actual radiation absorbed doses to tumors and normal liver tissue were calculated retrospectively based on the patient's 99mTc-MAA study and CT scans. As expected, the activity uptake within the liver was found to be highly nonuniform and multifold tumor to nontumor uptake was observed. A partition model was used to calculate the radiation absorbed dose within each region. For a typical patient the calculated radiation absorbed doses to the tumor and liver were 402 and 118 Gy, respectively. The radiation safety procedure involves confinement of the source and proper disposal of the contaminated materials. The average exposure rates at 1 m from the patients and on contact just anterior to the liver were 6 and 135 uSv/h, respectively. The special physics and dosimetry protocol developed for this procedure is presented.

Proteasome-independent disruption of PML oncogenic domains (PODs), but not covalent modification by SUMO-1, is required for human cytomegalovirus immediate-early protein IE1 to inhibit PML-mediated transcriptional repression.

Human cytomegalovirus (HCMV) major immediate-early protein IE1 is an abundant 72-kDa nuclear phosphoprotein that is thought to play an important role in efficient triggering of the lytic cycle, especially at low multiplicity of infection. The best-known properties of IE1 at present are its transient targeting to punctate promyelocytic leukemia protein (PML)-associated nuclear bodies (PML oncogenic domains [PODs] or nuclear domain 10 [ND10]), with associated displacement of the cellular PML tumor suppressor protein into a diffuse nucleoplasmic form and its association with metaphase chromosomes. Recent studies have shown that the targeting of PML (and associated proteins such as hDaxx) to PODs is dependent on modification of PML by ubiquitin-like protein SUMO-1. In this study, we provide direct evidence that IE1 is also covalently modified by SUMO-1 in both infected and cotransfected cells, as well as in in vitro assays, with up to 30% of the protein representing the covalently conjugated 90-kDa form in stable U373/IE1 cell lines. Lysine 450 was mapped as the major SUMO-1 conjugation site, but a point mutation of this lysine residue in IE1 did not interfere with its targeting to and disruption of the PODs. Surprisingly, unlike PML or IE2, IE1 did not interact with either Ubc9 or SUMO-1 in yeast two-hybrid assays, suggesting that some additional unknown intranuclear cofactors must play a role in IE1 sumoylation. Interestingly, stable expression of either exogenous PML or exogenous Flag-SUMO-1 in U373 cell lines greatly enhanced both the levels and rate of in vivo IE1 sumoylation during HCMV infection. Unlike the disruption of PODs by the herpes simplex virus type 1 IE110(ICP0) protein, the disruption of PODs by HCMV IE1 proved not to involve proteasome-dependent degradation of PML. We also demonstrate here that the 560-amino-acid PML1 isoform functions as a transcriptional repressor when fused to the GAL4 DNA-binding domain and that wild-type IE1 inhibits the repressor function of PML1 in transient cotransfection assays. Furthermore, both IE1(1-346) and IE1(L174P) mutants, which are defective in displacing PML from PODs, failed to inhibit the repression activity of PML1, whereas the sumoylation-negative IE1(K450R) mutant derepressed as efficiently as wild-type IE1. Taken together, our results suggest that proteasome-independent disruption of PODs, but not IE1 sumoylation, is required for efficient IE1 inhibition of PML-mediated transcriptional repression.

Effect of mdr1a P-glycoprotein gene disruption, gender, and substrate concentration on brain uptake of selected compounds.

PURPOSE: This study assessed the influence of mdr1a P-glycoprotein (P-gp) gene disruption, gender and concentration on initial brain uptake clearance (Clup) of morphine, quinidine and verapamil. METHODS: Clup of radiolabeled substrates was determined in P-gp-competent and deficient [mdr1a(-/-)] mice by in situ brain perfusion. Brain:plasma distribution of substrates after i.v. administration was determined in both strains. RESULTS: Genetic disruption of mdr1a P-gp resulted in 1.3-, 6.6- and 14-fold increases in Clup for morphine, verapamil and quinidine, respectively. With the exception of small differences for verapamil, gender did not affect Clup. Saturable transport of verapamil and quinidine was observed only in P-gp-competent mice, with apparent IC50 values for efflux of 8.6 +/- 2.3 microM and 36 +/- 2 microM, respectively. Verapamil Clup was approximately 50% higher in mdr1a(+/-) vs. mdr1a(+/+) mice; no such difference was observed for quinidine. In P-gp-competent mice, uptake of verapamil and quinidine was unaffected by organic vehicles. Plasma decreased VER Clup to a greater extent in the presence of P-gp. The influence of P-gp in situ was lower than, but correlated with, the effect in vivo. CONCLUSIONS: P-gp decreases Clup of morphine, verapamil and quinidine in situ with little or no influence of gender, but this effect cannot fully account for the effects of P-gp in vivo. P-gp is the only saturable transport mechanism for verapamil and quinidine at the murine blood-brain barrier. The influence of protein binding on Clup may be enhanced by P-gp-mediated efflux.

Seroepidemiology and molecular epidemiology of Kaposi's sarcoma-associated herpesvirus among Jewish population groups in Israel.

BACKGROUND: The incidence of classic Kaposi's sarcoma among Jews in Israel is among the highest in the developed world. Kaposi's sarcoma-associated herpesvirus (KSHV or human herpesvirus 8) is causally linked to Kaposi's sarcoma. Very little is known about the prevalence of KSHV in the Middle East or about the modes of transmission in Mediterranean countries. METHODS: From 1992 through 1995, sera were obtained from 1648 adults who had tested positive for hepatitis B virus (HBV) surface antigen 20 years earlier at blood donations; sera were also obtained from 2403 of their family members. All sera were tested for anti-KSHV antibodies with the use of an indirect immunofluorescence assay. To analyze the effects of various factors on the risk of KSHV infection for both the HBV-positive cohort and their families, logistic regression for cluster data and generalized estimating equations were used. All statistical tests were two-sided. RESULTS: Among family members, the seroprevalence of antibodies against KSHV was 9.9% (95% confidence interval [CI] = 8.7% to 11.1%); among the former blood donors who had tested positive for hepatitis B, it was 22% (95% CI = 19.9% to 24.1%). Overall, the best predictor of KSHV status was the place of birth. The most important risk factors found for both husband and wife to test KSHV positive were their own places of birth and their spouse's seropositivity. For a child to test positive, the most important risk factor was maternal seropositivity. CONCLUSIONS: The crude prevalence rate of KSHV among the Jewish population in Israel is 9.9%. Important routes of KSHV transmission in the families studied are spouse to spouse and mother to child. The presence of KSHV in Jews in Israel of all ethnic origins and their high incidence of reported Kaposi's sarcoma suggest that KSHV was introduced into the Jewish population prior to the major Diaspora.

Morphine antinociception is enhanced in mdr1a gene-deficient mice.

PURPOSE: Previous studies have suggested that P-glycoprotein (P-gp) modulates opioid antinociception for selected mu-and delta-agonists. This study was undertaken to assess morphine antinociception in mice lacking the mdr1a gene for expression of P-gp in the CNS. METHODS: Morphine (n = 4-5/group) was administered as a single s.c. dose to mdr1a(-/-) mice (3-5 mg/kg) or wild-type FVB controls (8-10 mg/kg). Tail-flick response to radiant heat, expressed as percent of maximum response (%MPR), was used to determine the antinociceptive effect of morphine. Concentrations in serum, brain tissue, and spinal cord samples obtained immediately after the tail-flick test were determined by HPLC with fluorescence detection. Parallel experiments with R(+)-verapamil, a chemical inhibitor of P-gp, also were performed to further investigate the effect of P-gp on morphine-associated antinociception. RESULTS: Morphine-associated antinociception was increased significantly in the mdr1a(-/-) mice. The ED50 for morphine was > 2-fold lower in mdr1a(-/-) (3.8+/-0.2 mg/kg) compared to FVB (8.8+/-0.2 mg/kg) mice. However, the EC50 derived from the brain tissue was similar between the two mouse strains (295 ng/g vs. 371 ng/g). Pretreatment with R(+)-verapamil produced changes similar to those observed in gene-deficient mice. P-gp does not appear to affect morphine distribution between spinal cord and blood, as the spinal cord:serum morphine concentration ratio was similar between gene-deficient and wild-type mice (0.47+/-0.03 vs. 0.56+/-0.04, p>0.05). CONCLUSIONS: The results of this study are consistent with the hypothesis that P-gp attenuates the antinociceptive action of morphine by limiting the brain:blood partitioning of the opioid.