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Polymerase chain reaction (PCR) was used to examine human herpesvirus 8 (HHV-8) DNA from Kaposi's sarcoma (KS) lesions, normal skin, and peripheral blood mononuclear cells (PBMC) from human immunodeficiency virus (HIV)-infected patients who did or did not have KS. Of 9 KS biopsies, 8 were positive for five HHV-8 open-reading frames and ranged from 1 viral genome per 2.5-12.7 cells. Two putative replicative gene RNAs were detected by reverse transcription-PCR at low levels in 1 KS lesion. HHV-8 DNA was detected in 4 of 8 PBMC samples from patients with KS and in 2 of 18 PBMC samples from patients without KS. Sera were tested for reactivity with BCBL-1 cells (HHV-8 positive): High immunofluorescence antibody titers against HHV-8 lytic and latent antigens were detected in samples from KS-positive patients, and >20 polypeptides from induced BCBL-1 cells were recognized. Sera from 6 of 18 patients without KS showed low levels of antibodies against HHV-8 lytic and latent antigens. [ABSTRACT FROM AUTHOR]

Amyotrophic lateral sclerosis (ALS) patients lack effective treatments to maintain motor and neuromuscular function. This study aimed to evaluate the effect of a home-based exercise program on muscle strength, ALS scores, and transcriptome in ALS patients, Clinical Trials.gov #NCT03201991 (28/06/2017). An open-label, non-randomized pilot clinical trial was conducted in seven individuals with early-stage ALS. Participants were given 3 months of home-based resistance exercise focusing on the quadriceps muscles. The strength of exercised muscle was evaluated using bilateral quadriceps strength with manual muscle testing, handheld dynamometers, five times sit-to-stand, and Timed-Up-and-Go before and after the exercise program. In addition, changes in the Sickness Impact Profile ALS-19 (SIP/ALS-19) as the functional outcome measure and the transcriptome of exercised muscles were compared before and after the exercise. The primary outcome of muscle strength did not change significantly by the exercise program. The exercise program maintained the SIP/ALS-19 and the ALS Functional Rating Scale-Revised (ALSFRS-R). Transcriptome analysis revealed that exercise reverted the expression level of genes decreased in ALS, including parvalbumin. Three months of moderately intense strength and conditioning exercise maintained muscle strength of the exercised muscle and ALSFRS-R scores and had a positive effect on patients' muscle transcriptome., (© 2024. The Author(s).)

Aim: Neurological adverse events (NAEs) are infrequent immune checkpoint inhibitor (ICI) outcomes poorly characterized in extant research, complicating their clinical management. Methods: This study characterized the frequency, severity, patterning and timing of NAEs using a large retrospective registry, including all patients who received at least one dose of an ICI from 2/1/2011-4/7/2022 within our health network. Results: Among 3137 patients, there were 54 NAEs (1.72% any grade; 0.8% grade 3-4). Most NAEs were peripheral (57.4%) versus central (42.6%). Melanoma and renal cell carcinoma were significantly associated with NAEs. Conclusion: The incidence of NAEs was rare though higher than many prior case estimates; the timing was consistent with other AEs. NAEs frequently occurred in tumor types known to favor brain metastases.

Autism Spectrum Disorder (ASD) has been associated with a complex interplay between genetic and environmental factors. Prenatal stress exposure has been identified as a possible risk factor, although most stress-exposed pregnancies do not result in ASD. The serotonin transporter (SERT) gene has been linked to stress reactivity, and the presence of the SERT short (S)-allele has been shown to mediate the association between maternal stress exposure and ASD. In a mouse model, we investigated the effects of prenatal stress exposure and maternal SERT genotype on offspring behavior and explored its association with maternal microRNA (miRNA) expression during pregnancy. Pregnant female mice were divided into four groups based on genotype (wildtype or SERT heterozygous knockout (Sert-het)) and the presence or absence of chronic variable stress (CVS) during pregnancy. Offspring behavior was assessed at 60 days old (PD60) using the three-chamber test, open field test, elevated plus-maze test, and marble-burying test. We found that the social preference index (SPI) of SERT-het/stress offspring was significantly lower than that of wildtype control offspring, indicating a reduced preference for social interaction on social approach, specifically for males. SERT-het/stress offspring also showed significantly more frequent grooming behavior compared to wildtype controls, specifically for males, suggesting elevated repetitive behavior. We profiled miRNA expression in maternal blood samples collected at embryonic day 21 (E21) and identified three miRNAs (mmu-miR-7684-3p, mmu-miR-5622-3p, mmu-miR-6900-3p) that were differentially expressed in the SERT-het/stress group compared to all other groups. These findings suggest that maternal SERT genotype and prenatal stress exposure interact to influence offspring behavior, and that maternal miRNA expression late in pregnancy may serve as a potential marker of a particular subtype of ASD pathogenesis.

Background/introduction: As the most common form of pre-invasive breast cancer, ductal carcinoma in situ (DCIS) affects over 50,000 women in the US annually. Despite standardized treatment involving lumpectomy and radiation therapy, up to 25% of patients with DCIS experience disease recurrence often with invasive ductal carcinoma (IDC), indicating that a subset of patients may be under-treated. As most DCIS cases will not progress to invasion, many patients may experience over-treatment. By understanding the underlying processes associated with DCIS to IDC progression, we can identify new biomarkers to determine which DCIS cases may become invasive and improve treatment for patients. Accumulation of fibroblasts in IDC is associated with disease progression and reduced survival. While fibroblasts have been detected in DCIS, little is understood about their role in DCIS progression., Goals: We sought to determine 1) whether DCIS fibroblasts were similar or distinct from normal and IDC fibroblasts at the transcriptome level, and 2) the contributions of DCIS fibroblasts to breast cancer progression., Methods: Fibroblasts underwent transcriptome profiling and pathway analysis. Significant DCIS fibroblast-associated genes were further analyzed in existing breast cancer mRNA databases and through tissue array immunostaining. Using the sub-renal capsule graft model, fibroblasts from normal breast, DCIS and IDC tissues were co-transplanted with DCIS.com breast cancer cells., Results: Through transcriptome profiling, we found that DCIS fibroblasts were characterized by unique alterations in cell cycle and motility related genes such as PKMYT1, TGF-α, SFRP1 and SFRP2, which predicted increased cell growth and invasion by Ingenuity Pathway Analysis. Immunostaining analysis revealed corresponding increases in expression of stromal derived PKMYT1, TGF-α and corresponding decreases in expression of SFRP1 and SFRP2 in DCIS and IDC tissues. Grafting studies in mice revealed that DCIS fibroblasts enhanced breast cancer growth and invasion associated with arginase-1+ cell recruitment., Conclusion: DCIS fibroblasts are phenotypically distinct from normal breast and IDC fibroblasts, and play an important role in breast cancer growth, invasion, and recruitment of myeloid cells. These studies provide novel insight into the role of DCIS fibroblasts in breast cancer progression and identify some key biomarkers associated with DCIS progression to IDC, with important clinical implications., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Fang, Medrano, Cote, Portsche, Rao, Hong, Behbod, Knapp, Bloomer, Noel-Macdonnell and Cheng.)

To evaluate movement quality of upper limb (UL) prosthesis users, performance-based outcome measures have been developed that examine the normalcy of movement as compared to a person with a sound, intact hand. However, the broad definition of "normal movement" and the subjective nature of scoring can make it difficult to know which areas of the body to evaluate, and the expected magnitude of deviation from normative movement. To provide a more robust approach to characterizing movement differences, the goals of this work are to identify degrees of freedom (DOFs) that will inform abnormal movement for several tasks using unsupervised machine learning (clustering methods) and elucidate the variations in movement approach across two upper-limb prosthesis devices with varying DOFs as compared to healthy controls. 24 participants with no UL disability or impairment were recruited for this study and trained on the use of a body-powered bypass (n = 6) or the DEKA limb bypass (n = 6) prosthetic devices or included as normative controls. 3D motion capture data were collected from all participants as they performed the Jebsen-Taylor Hand Function Test (JHFT) and targeted Box and Blocks Test (tBBT). Range of Motion, peak angle, angular path length, mean angle, peak angular velocity, and number of zero crossings were calculated from joint angle data for the right/left elbows, right/left shoulders, torso, and neck and fed into a K-means clustering algorithm. Results show right shoulder and torso DOFs to be most informative in distinguishing between bypass user and norm group movement. The JHFT page turning task and the seated tBBT elicit movements from bypass users that are most distinctive from the norm group. Results can be used to inform the development of movement quality scoring methodology for UL performance-based outcome measures. Identifying tasks across two different devices with known variations in movement can inform the best tasks to perform in a rehabilitation setting that challenge the prosthesis user's ability to achieve normative movement., Competing Interests: The authors have declared that no competing interests exist.

Objectives: To study the effects of advancements in upper-limb prosthesis technology on the user through biomechanical analyses at the joint level to quantitatively examine movement differences of individuals using an advanced upper-limb device, the DEKA Arm, and a conventional device, a body-powered Hosmer hook., Design: Clinical measurement., Setting: Laboratories at the United States Food and Drug Administration., Participants: Convenience sample of participants (N=14) with no upper limb disability or impairment., Interventions: All participants were trained on either an upper limb body-powered (n=6) or DEKA Arm (n=8) bypass device., Main Outcome Measures: Participants completed the Jebsen-Taylor Hand Function Test (JHFT) and targeted Box and Blocks Test within a motion capture framework. Task completion times and joint angle trajectories for each degree of freedom of the right elbow, right shoulder, and torso were collected and analyzed for range of motion, mean angle, maximum angle, and angle path length during each task., Results: Significant differences between devices were observed across metrics in at least one task for each degree of freedom. Completion times were significantly higher for DEKA users (eg, 30.51±19.29s vs 9.30±1.44s) for JHFT-simulated feeding. Some kinematic measures, such as angle path length, were significantly lower in DEKA users, with the greatest difference in the right elbow flexion path length during JHFT-Page Turning (0.29±0.14 units vs 0.11±0.04 units)., Conclusions: Results from this work elucidate the effect of the device on the user's movement approach and performance, as well as emphasizing the importance of capturing movement quality into the assessment of function for advanced prosthetic technology to fully understand and evaluate potential benefits.

Tg26 mice are robust models of human immunodeficiency virus 1 associated nephropathy (HIVAN). These mice are useful for HIVAN pathology analysis, and recent studies suggest that the Tg26 mouse model is an excellent model of other chronic kidney diseases. We performed RNA seq analysis of differential gene expression in the kidneys of Tg26 mice. Kidneys were collected from Tg26 mice and wildtype (WT) littermates at 3 months of age. The raw data were analyzed for differential gene expression using a negative binomial generalized linear model in the DeSeq2 software package. We used P -Value ≤0.05 and an absolute fold change of 1.5 to identify top 50 upregulated and top 50 downregulated differentially expressed genes between the WT and Tg26 mice. As expected inflammatory genes were among the top differentially regulated genes. Our data provides yet another level of information to help gain a more comprehensive understanding of disease progression and identify potential drug targets for HIVAN and chronic kidney diseases., (© 2020 The Author(s).)

Motor learning and compensatory movement are important aspects of prosthesis training yet relatively little quantitative evidence supports our current understanding of how motor control and compensation develop in the novel body-powered prosthesis user. The goal of this study is to assess these aspects of prosthesis training through functional, kinematic, and kinetic analyses using a within-subject paradigm compared across two training time points. The joints evaluated include the left and right shoulders, torso, and right elbow. Six abled-bodied subjects (age 27 ± 3) using a body-powered bypass prosthesis completed the Jebsen-Taylor Hand Function Test and the targeted Box and Blocks Test after five training sessions and again after ten sessions. Significant differences in movement parameters included reduced times to complete tasks, reduced normalized jerk for most joints and tasks, and more variable changes in efficiency and compensation parameters for individual tasks and joints measured as range of motion, maximum angle, and average moment. Normalized jerk, joint specific path length, range of motion, maximum angle, and average moment are presented for the first time in this unique training context and for this specific device type. These findings quantitatively describe numerous aspects of motor learning and control in able-bodied subjects that may be useful in guiding future rehabilitation and training of body-powered prosthesis users., Competing Interests: The authors have declared that no competing interests exist.

Study Design: Clinical measurement; 22 subjects with no upper limb disability completed the Jebsen-Taylor Hand Function Test (JHFT)., Introduction: To realize the potential of 3D motion capture to augment evaluation of individuals with upper limb disability/impairment, it is important to understand the expected kinematic motion that characterizes performance during functional evaluation., Purpose of the Study: To assess kinematic variability and establish kinematic patterns for the JHFT., Methods: Upper body joint kinematics were collected using a Vicon motion capture system. Average range of motion and maximum angle were calculated for all tasks. Intrasubject and intersubject variability were assessed by calculating Pearson's correlation coefficient, adjusted coefficient of multiple correlation (CMC adj ), and standard deviation for 10 joint angles at the wrist, elbow, shoulder, and torso., Results: The writing and picking up small objects tasks generally had high intrasubject variability, with most joint angles having median Pearson's correlation coefficients lower than 0.7. The CMC adj values were generally greater than 0.5 for elbow, shoulder, and torso joints during can-lifting tasks, indicating high consistency in those kinematic trajectories across subjects. Low consistency across subjects in all joint angles was observed for writing (CMC adj  < 0.07; SD max  > 10°)., Discussion: Kinematic patterns for the JHFT tasks were analyzed., Conclusions: With kinematic patterns for the JHFT tasks analyzed, optimal patterns of activity performance can be defined, allowing for easier identification and adjustment of atypical motion. Results can be used to inform selection of tasks for kinematic evaluation and provide expected variability for comparison to patient populations, which is useful for regulatory review and clinical assessment., (Published by Elsevier Inc.)

Objective: To evaluate the impact of the Canterbury earthquakes on the mental health of older people by examining dispensing patterns of psychotropic medication., Method: Dispensing data from community pharmacies for antidepressants, antipsychotics, anxiolytics, and sedative/hypnotics are routinely recorded in a national database. Longitudinal data are available for residents of the Canterbury District Health Board (DHB) (n = 67 760 at study onset) and the rest of New Zealand (n = 469 055 at study onset). We compared older age dispensing data between 2008 and 2018 for Canterbury DHB with older age dispensing data nationally in order to assess the impact of the Canterbury earthquakes on the mental health of older persons., Results: Older age residents of Canterbury are dispensed antidepressants, antipsychotics, and anxiolytics at higher rates than national comparators, but this finding predated the onset of the earthquakes. Short-term increases in anxiolytic and sedative/hypnotic dispensing occurred for the month following the February 2011 earthquake. No other short- or longer-term increases in dispensing of psychiatric medication were present., Conclusion: The February 2011 Canterbury earthquake caused a short-term increase in dispensing of anxiolytics and sedative/hypnotics. No longer-term effects on dispensing were observed. This suggests that older persons sought assistance for insomnia and anxiety in the aftermath of the most devastating earthquake, but longer-term rates of clinically significant anxiety and depression for older persons did not increase as a consequence of the earthquakes sequence., (© 2019 John Wiley & Sons, Ltd.)

Colorectal cancer (CRC) is a high burden disease with several genes involved in tumor progression. The aim of the present study was to identify, generate and clinically validate a novel gene signature to improve prediction of overall survival (OS) to effectively manage colorectal cancer. We explored The Cancer Genome Atlas (TCGA), COAD and READ datasets (597 samples) from The Protein Atlas (TPA) database to extract a total of 595 candidate genes. In parallel, we identified 29 genes with perturbations in > 6 cancers which are also affected in CRC. These genes were entered in cBioportal to generate a 17 gene panel with highest perturbations. For clinical validation, this gene panel was tested on the FFPE tissues of colorectal cancer patients (88 patients) using Nanostring analysis. Using multivariate analysis, a high prognostic score (composite 4 gene signature- DPP7/2 , YWHAB , MCM4 and FBXO46 ) was found to be a significant predictor of poor prognosis in CRC patients (HR: 3.42, 95% CI: 1.71-7.94, p < 0.001 *) along with stage (HR: 4.56, 95% CI: 1.35-19.15, p = 0.01 *). The Kaplan-Meier analysis also segregated patients on the basis of prognostic score (log-rank test, p = 0.001 *). The external validation using GEO dataset (GSE38832, 122 patients) corroborated the prognostic score (HR: 2.7, 95% CI: 1.99-3.73, p < 0.001 *). Additionally, higher score was able to differentiate stage II and III patients (130 patients) on the basis of OS (HR: 2.5, 95% CI: 1.78-3.63, p < 0.001 *). Overall, our results identify a novel 4 gene prognostic signature that has clinical utility in colorectal cancer.

We aim to present a standard protocol for training able-bodied individuals to use a body-powered bypass prosthesis and assess training length and impact of prepositioning. The protocol design and subsequent analysis aims to facilitate controlled and efficient implementation of the able-bodied bypass user in the research setting. Six volunteers completed ten two-hour sessions with a body-powered bypass prosthesis. Each session included standardized training tasks: object manipulation, free training, and activities of daily living. Two outcome measures, a modified Southampton Hand Assessment Procedure and the Box and Blocks Test were used to score performance during each session. A standard learning curve was fitted to the scores to determine an optimal training length based on learning rate and learning plateau values; further tested through an effect size calculation. To assess prepositioning, scores were normalized and grouped by a measure of terminal device rotations. Scores then underwent a linear regression analysis. Optimal training lengths were found to be three and six sessions for modified Southampton Hand Assessment Procedure and Box and Blocks Test results respectively, with support from effect size calculations. Prepositioning and normalized score were weakly correlated, +0.38, and poorly fit, R 2 = 0.016, contradictory to the expected strong correlation that would accompany the supposed performance benefits attributed to prepositioning. A lack of resources to guide the use of upper limb bypass prostheses is addressed with the presented standard, quantitatively assessed protocol. A framework for evaluating adequate training length and prepositioning is established and shared.

The present study attempted to identify critical symptom domains of individuals with Myalgic Encephalomyelitis (ME) and chronic fatigue syndrome (CFS). Using patient and control samples collected in the United States, Great Britain, and Norway, exploratory factor analysis (EFA) was used to establish the underlying factor structure of ME and CFS symptoms. The EFA suggested a four-factor solution: post-exertional malaise, cognitive dysfunction, sleep difficulties, and a combined factor consisting of neuroendocrine, autonomic, and immune dysfunction symptoms. The use of empirical methods could help better understand the fundamental symptom domains of this illness.

Current genomic studies are limited by the availability of fresh tissue samples. Here, we show that Illumina RNA sequencing of formalin-fixed diagnostic tumor samples produces gene expression that is strongly correlated with matched frozen tumor samples (r > 0.89). In addition, sequence variations identified from FFPE RNA show 99.67% concordance with that from exome sequencing of matched frozen tumor samples. Because FFPE is a routine diagnostic sample preparation, the feasibility results reported here will facilitate the setup of large-scale research and clinical studies in medical genomics that are currently limited by the availability of fresh frozen samples.

Background: Lifetime histories of sexual and physical abuse have been associated with increased HIV-risk sexual behavior, and some studies have identified other variables associated with these relationships. However, there is a dearth of literature that has critically examined abuse histories and HIV-risk sexual behavior in relation to these other variables., Objectives: Predictors of HIV-risk sexual behavior were analyzed among a sample of ex-offenders who were completing inpatient substance dependence treatment to identify factors related to increases in HIV-risk sexual behavior beyond that of abuse histories., Design: Hierarchical linear regression was conducted to examine sociodemographic characteristics, recent substance use, and current psychiatric problem severity in addition to lifetime histories of sexual/physical abuse in a cross-sectional design., Results: Gender, substance use, and psychiatric problem severity predicted increases in HIV-risk sexual behavior beyond what was predicted by abuse histories. Proportionately more women than men reported abuse histories. In addition, significantly more unprotected sexual than safer sexual practices were observed, but differences in these practices based on lifetime abuse histories and gender were not significant., Conclusions: Findings suggest recent substance use and current psychiatric problem severity are greater risk factors for HIV-risk sexual behavior than lifetime abuse histories among persons who have substance use disorders.

We report a case of anesthesia for elective outpatient third molar extraction in a juvenile with Leigh disease, a progressive neurodegenerative disorder related to respiratory chain deficiency. This syndrome usually presents in infancy and is characterized by nervous system dysfunction and respiratory abnormalities. Anesthesia has been reported to aggravate respiratory symptoms and frequently precipitate respiratory failure. Preoperative swallowing difficulty or respiratory symptoms should be carefully diagnosed, because they can be a warning sign of postoperative complications or mortality. Adverse effects of anesthesia may quickly lead into metabolic acidosis. Anesthetics should be carefully chosen that do not interfere with mitochondrial respiration, which can lead to lactic acidosis.

Kaposi's sarcoma-associated herpesvirus (KSHV) infection of in vitro target cells is characterized by the expression of the latency-associated open reading frame (ORF) 73 gene (LANA-1) and the absence of progeny virus production. This default latent infection can be switched into lytic cycle by phorbol ester and by the lytic cycle ORF 50 (RTA) protein. In this study, the kinetics of latent and lytic gene expression immediately following KSHV infection of primary human dermal microvascular endothelial (HMVEC-d) and foreskin fibroblast (HFF) cells were examined by real-time reverse transcriptase PCR and whole-genome array. Within 2 h postinfection (p.i.), high levels of ORF 50 transcripts were detected in both cell types, which declined sharply by 24 h p.i. In contrast, comparatively low levels of ORF 73 expression were detected within 2 h p.i., increased subsequently, were maintained at a steady state, and declined slowly by 120 h p.i. The RTA and LANA-1 proteins were detected in the majority of infected cells by immunoperoxidase assays. In genome array, only 29 of 94 (31%) KSHV genes were expressed, which included 11 immediate-early/early, 8 early, and 5 late lytic genes and 4 latency-associated genes. While the expression of latent ORF 72, 73, and K13 genes continued, nearly all of the lytic genes declined or were undetectable by 8 and 24 h p.i. in HMVEC-d and HFF cells, respectively. Only a limited number of RTA-activated KSHV genes were expressed briefly, and the majority of KSHV genes involved in viral DNA synthesis and structural proteins were not expressed. However, early during infection, the lytic K2, K4, K5, K6, and vIRF2 genes with immune modulation functions and the K7 gene with antiapoptotic function were expressed. Expression of K5 was detected for up to 5 days of observation, and vIRF2 was expressed up to 24 h p.i. The full complement of lytic cycle genes were expressed when 12-O-tetradecanoylphorbol-13-acetate was added to the HMVEC-d cells after 48 h p.i. These data suggest that in contrast to alpha- and betaherpesviruses and some members of gammaherpesviruses, gamma-2 KSHV in vitro infection is characterized by the concurrent expression of latent and a limited number of lytic genes immediately following infection and a subsequent decline and/or absence of lytic gene expression with the persistence of latent genes. Expression of its limited lytic cycle genes could be a "strategy" that evolved in KSHV allowing it to evade the immune system and to provide the necessary factors and time to establish and/or maintain latency during the initial phases of infection. These are unique observations among in vitro herpesvirus infections and may have important implications in KSHV biology and pathogenesis.

Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8) is etiologically linked to the endothelial tumor Kaposi's sarcoma and with two lymphoproliferatve disorders, primary effusion lymphoma and multicentric Castleman's disease. HHV-8 infects a variety of target cells both in vivo and in vitro, binds to the in vitro target cells via cell surface heparan sulfate, and uses the alpha(3)beta(1) integrin as one of the entry receptors. Within minutes of infection, HHV-8 induced the integrin-mediated signaling pathways and morphological changes in the target cells (S. M. Akula et al., Cell, 108: 407-419, 2002; P. P. Naranatt et al., J. Virol., 77: 1524-1539, 2003). As an initial step toward understanding the role of host genes in HHV-8 infection and pathogenesis, modulation of host cell gene expression immediately after infection was examined. To reflect HHV-8's broad cellular tropism, mRNAs collected at 2 and 4 h after infection of primary human endothelial [human adult dermal microvascular endothelial cells (HMVECd)] and foreskin fibroblast [human foreskin fibroblast (HFF)] cells and human B cell line (BJAB) were analyzed by oligonucleotide array with approximately 22,000 human transcripts. With a criteria of >2-fold gene induction as significant, approximately 1.72% of the genes were differentially expressed, of which, 154 genes were shared by at least two cells and 33 genes shared by all three cells. HHV-8-induced transcriptional profiles in the endothelial and fibroblast cells were closely similar, with substantial differences in the B cells. In contrast to the antiapoptotic regulators induced in HMVECd and HFF cells, proapoptotic regulators were induced in the B cells. A robust increase in the expression of IFN-induced genes suggestive of innate immune response induction was observed in HMVECd and HFF cells, whereas there was a total lack of immunity related protein inductions in B cells. These striking cell type-specific behaviors suggest that HHV-8-induced host cell gene modulation events in B cells may be different compared with the adherent endothelial and fibroblast target cells. Functional clustering of modulated genes identified several host molecules hitherto unknown to HHV-8 infection. These results indicate that early during infection, HHV-8 reprograms the host transcriptional machinery regulating a variety of cellular processes including apoptosis, transcription, cell cycle regulation, signaling, inflammatory response, and angiogenesis, all of which may play important roles in the biology and pathogenesis of HHV-8.

Background: Functional imaging studies have recently demonstrated that specific brain regions become active in cocaine addicts when they are exposed to cocaine stimuli. To test whether there are regional brain activity differences during alcohol cue exposure between alcoholic subjects and social drinkers, we designed a functional magnetic resonance imaging (fMRI) protocol involving alcohol-specific cues., Methods: Ten non-treatment-seeking adult alcoholic subjects (2 women) (mean [SD] age, 29.9 [9.9] years) as well as 10 healthy social drinking controls of similar age (2 women) (mean [SD] age, 29.4 [8.9] years) were recruited, screened, and scanned. In the 1.5-T magnetic resonance imaging scanner, subjects were serially rated for alcohol craving before and after a sip of alcohol, and after a 9-minute randomized presentation of pictures of alcoholic beverages, control nonalcoholic beverages, and 2 different visual control tasks. During picture presentation, changes in regional brain activity were measured with the blood oxygen level-dependent technique., Results: Alcoholic subjects, compared with the social drinking subjects, reported higher overall craving ratings for alcohol. After a sip of alcohol, while viewing alcohol cues compared with viewing other beverage cues, only the alcoholic subjects had increased activity in the left dorsolateral prefrontal cortex and the anterior thalamus. The social drinkers exhibited specific activation only while viewing the control beverage pictures., Conclusions: When exposed to alcohol cues, alcoholic subjects have increased brain activity in the prefrontal cortex and anterior thalamus-brain regions associated with emotion regulation, attention, and appetitive behavior.

Objective: The purpose of this study was to evaluate whether immediate placement of medicated dry socket packing would decrease the incidence of alveolar osteitis (dry socket) with lower third molar extractions., Study Design: In 100 patients, 200 lower third molars were extracted. One half of the sockets were packed to the crest of the alveolar ridge with a one-quarter-inch radiograph-detectable filament gauze that contained 9% eugenol, 36% balsam of Peru, and 55% petroleum jelly. The medicated packing was removed 1 week after surgery. None of the patients were taking antibiotics. Patients were instructed to increase their oral hygiene before and after surgery and were to use 0.12% chlorhexidine gluconate 2 days before and 3 days after surgery. RESULTS; Two hundred bilateral lower third molars of varying difficulty were extracted. The overall alveolar osteitis rate was 34 (17%). The immediately packed lower third molar sites had an alveolar osteitis rate of 8 (8%). The sockets that were not packed with medicated packing the day of surgery had an alveolar osteitis rate of 26 (26%). The difference was statistically significant (P =.001)., Conclusion: The results of this study suggest that placement of medicated dry socket packing immediately after lower third molar extraction decreases the alveolar osteitis rate.

While parenting is a universal human behavior, its neuroanatomic basis is currently unknown. Animal data suggest that the cingulate may play an important function in mammalian parenting behavior. For example, in rodents cingulate lesions impair maternal behavior. Here, in an attempt to understand the brain basis of human maternal behavior, we had mothers listen to recorded infant cries and white noise control sounds while they underwent functional MRI (fMRI) of the brain. We hypothesized that mothers would show significantly greater cingulate activity during the cries compared to the control sounds. Of 7 subjects scanned, 4 had fMRI data suitable for analysis. When fMRI data were averaged for these 4 subjects, the anterior cingulate and right medial prefrontal cortex were the only brain regions showing statistically increased activity with the cries compared to white noise control sounds (cluster analysis with one-tailed z-map threshold of P < 0.001 and spatial extent threshold of P < 0.05). These results demonstrate the feasibility of using fMRI to study brain activity in mothers listening to infant cries and that the anterior cingulate may be involved in mothers listening to crying babies. We are currently replicating this study in a larger group of mothers. Future work in this area may help (1) unravel the functional neuroanatomy of the parent-infant bond and (2) examine whether markers of this bond, such as maternal brain response to infant crying, can predict maternal style (i.e., child neglect), offspring temperament, or offspring depression or anxiety.

Studies of Alzheimer's disease patients show that individuals with larger premorbid brains have a later onset of disease, or a lessened severity of cognitive impairment, or both. This may be due to a "functional reserve" associated with the greater number of neurons and synapses available in larger brains. We used magnetic resonance imaging and the MicroCog Assessment of Cognitive Functioning to examine the association between intracranial volume (premorbid brain size) and neuropsychological function in abstinent crack-cocaine and crack-cocaine-alcohol dependent individuals. There were no significant differences between the crack-only and the crack-alcohol dependent participants in neuropsychological performance or in intracranial volume. The abstinent cocaine-dependent individuals (both crack-only and crack-alcohol) were significantly impaired in many neuropsychological domains. Intracranial volume accounted for a significant proportion of the variance in neuropsychological performance. This result is consistent with the finding in the Alzheimer's literature that larger brains can maintain function to a greater degree, or for a longer period of time, in the face of cerebral disease or insult. Functional reserve may be a heretofore little recognized protective mechanism of the brain that has consequences for the severity of expression of cerebral disease or insult throughout life.

A cDNA library from phorbol ester-induced human herpesvirus-8 (HHV-8) carrying BCBL-1 cells was screened with an HIV+KS+ serum, and several cDNA clones encoding HHV-8 proteins were identified. Sequence analysis of two full-length cDNA clones show open reading frames (ORFs) encoded by spliced messages originating from the HHV-8 K8.1 gene. One cDNA encodes an ORF of 228 amino acids, designated K8. 1.A, with a cleavable signal sequence, a transmembrane domain, and four N-glycosylation sites. The splicing event generated the transmembrane domain in the ORF not seen in the genomic K8.1 ORF. Another cDNA encodes an ORF of 167 amino acids, designated K8.1.B, that shares similar amino and carboxyl termini with ORF K8.1.A but with an in-frame deletion. The primary translation products of ORF K8.1A (34 kDa) and K8.1B (20 kDa) in the in vitro-transcription-translation experiments shifted into glycosylated species of 43 and 32 kDa, respectively, in the presence of microsomal membranes. This suggested that the ORF K8.1A and K8.1B encode for glycoproteins. Riboprobes from the K8.1A cDNA insert hybridized with an HHV-8-specific 0.9-kb abundant transcript from BCBL-1 cells. Synthesis of this RNA was eliminated in the presence of a DNA synthesis inhibitor, suggesting that this RNA was a late gene transcript. Because ORFs K8.1A and K8.1B are unique for HHV-8, human sera were tested in Western blot reactions for antibodies against glutathione-S-transferase-ORF K8.1A fusion protein. All sera that were positive for HHV-8 antibodies in immunofluorescence assays with phorbol ester-induced BCBL-1 cells were also positive for anti-ORF K8.1A antibodies. This suggests that measurement of anti-ORF K8.1A antibodies would provide an HHV-8-specific serological assay. Further work is needed to define the biological role of the HHV-8 ORF K8.1A and K8.1B glycoproteins., (Copyright 1998 Academic Press.)