Pair bonding and disruption impact lung transcriptome in monogamous Peromyscus californicus.

Social interactions affect physiological and pathological processes, yet their direct impact in peripheral tissues remains elusive. Recently we showed that disruption of pair bonds in monogamous Peromyscus californicus promotes lung tumorigenesis, pointing to a direct effect of bonding status in the periphery (Naderi et al., 2021). Here we show that lung transcriptomes of tumor-free Peromyscus are altered in a manner that depends on pair bonding and superseding the impact of genetic relevance between siblings. Pathways affected involve response to hypoxia and heart development. These effects are consistent with the profile of the serum proteome of bonded and bond-disrupted Peromyscus and were extended to lung cancer cells cultured in vitro, with sera from animals that differ in bonding experiences. In this setting, the species' origin of serum (deer mouse vs FBS) is the most potent discriminator of RNA expression profiles, followed by bonding status. By analyzing the transcriptomes of lung cancer cells exposed to deer mouse sera, an expression signature was developed that discriminates cells according to the history of social interactions and possesses prognostic significance when applied to primary human lung cancers. The results suggest that present and past social experiences modulate the expression profile of peripheral tissues such as the lungs, in a manner that impacts physiological processes and may affect disease outcomes. Furthermore, they show that besides the direct effects of the hormones that regulate bonding behavior, physiological changes influencing oxygen metabolism may contribute to the adverse effects of bond disruption.

Coordination in the unfolded protein response during aging in outbred deer mice.

Endoplasmic reticulum (ER) stress has been linked to various metabolic pathologies, neurodegeneration and aging. Although various mechanistic aspects of the resulting unfolded protein response (UPR) have been elucidated, its regulation in genetically diverse populations remains elusive. In the present study we evaluated the expression of chaperones BiP/GRP78, GRP94 and calnexin (CANX) in the lungs, liver and brain of 7 months old and 2-3 years old outbred deer mice P. maniculatus and P. leucopus. Chaperones' expression was highly variable between species, tissues and ages suggesting that levels of expression of individual chaperones do not change consistently during aging. Despite this variation, a high degree of coordination was maintained between chaperones' expression indicating the tight regulation of the UPR which is consistent with its adaptive activity to maintain homeostasis. In the brain though of older P. maniculatus, at which neurodegenerative changes were detected, loss of coordination was revealed, especially between BiP and either of GRP94 or calnexin which indicates that de-coordination rather than aberrant expression is linked to deregulation of the UPR in aging. These findings underscore the involvement of UPR in the onset of aging-related pathologies and suggest that beyond levels of expression, concerted activation may be of significance to attain homeostasis. These findings emphasize the value of genetically diverse models and suggest that beyond levels of expression of individual targets the coordination of transcriptional networks should be considered when links to pathology are explored.

In vivo microdialysis of glutamate in ventroposterolateral nucleus of thalamus following electrolytic lesion of spinothalamic tract in rats.

Central pain is one of the most important complications after spinal cord injury (SCI), and thereby, its treatment raises many challenges. After SCI, in a cascade of molecular events, a marked increase in glutamate at the injury site results in secondary changes which may impact on supraspinal regions, mainly ventroposterolateral (VPL). There is little information about the changes in glutamate metabolism in the VPL and whether it contributes to SCI-related central pain. The present study was performed to evaluate glutamate release in the VPL following electrolytic lesion of spinothalamic tract (STT). A laminectomy was performed at spinal segments of T9-T10 in male rats, and then, unilateral electrolytic lesions were made in the STT. Glutamate concentrations in ipsilateral VPL dialysate were measured by HPLC method at days 3, 7, 14, 21 and 28 post-injury. Tactile pain and motor activity were also examined. Glutamate levels were significantly increased in ipsilateral VPL of spinal-cord-injured rats 2 weeks after SCI and remained high up to day 28 post-surgery. The STT lesions had no marked effect on our measures of motor activity, but there was a significant decrease in paw withdrawal threshold in the hind paws at day 14 post-SCI. These findings suggest that an increased release of glutamate in VPL plays a role in secondary pathologic changes, leading to neuronal hyperexcitation and neuropathic pain after SCI.

Ultra-rapid opiate detoxification followed by nine months of naltrexone maintenance therapy in Iran.

INTRODUCTION: The aim of this retrospective study was to assess ultra-rapid opiate detoxification (UROD) and to estimate the retention rate in naltrexone maintenance treatment. METHODS: 45 opiate-addicted male patients (DSM-IV 304.00; opiate per oral or per inhalation n=40, heroin intravenous n=5; concomitant cannabis abuse n=6) were detoxified by 6 h of naloxone infusion under general anesthesia with midazolam, propofol, clonidine and atracurium. Withdrawal signs were evaluated by the objective opiate withdrawal scale (OOWS, range 0-13) up to 24 h after awakening. After UROD, naltrexone 50 mg/day was prescribed for 9 months with assessments in 4-week intervals. RESULTS: Adverse events after UROD were prolonged unconsciousness (n=1), transient confusion (n=8) and depressive mood (n=6). The total sample showed a median OOWS score of 2 (mild withdrawal syndrome). The only two extreme outliers were found only in the subgroups "intravenous" (score 8) and "cannabis" (score 11). 96% (43/45) of the patients could be discharged the day after UROD. Thirty-six patients (80%) continued naltrexone therapy for the entire 9-month observation period. DISCUSSION: UROD and subsequently induction of naltrexone maintenance therapy can be regarded as safe and effective in patients with pure opiate addiction. Owing to cultural and economical factors our Iranian results may not correspond to European and American treatment modalities.

Detection of enterotoxigenic Staphylococcus aureus isolates in domestic dairy products.

BACKGROUND AND OBJECTIVES: Staphylococcus aureusis a one of THE most frequent causes of food poisoning (FP) in dairy products. The main etiologic agents of FP are staphylococcal enterotoxins (SE). There are different types of SE; types A (SEA) and B (SEB) are the most clinically important enterotoxins. Traditional dairy products are still produced in small batches and sold by some vendors without a permit from the Ministry of Health. This study focuses on the molecular and serological detection of enterotoxigenic Staphylococcus aureus SEA and SEB genes and its products, respectively from samples of such traditional products. MATERIALS AND METHODS: 100 samples from dairy products were produced under sterile conditions via traditional methods and were transported to the laboratory. The samples were cultured and identified by routine bacteriological methods. The isolated bacteria were evaluated by PCR tests for detection of the genes encoding SEA and SEB. Subsequently, the ability of these strains to produce enterotoxin was examined by Sac's culture method and was confirmed by Sigel Radial Immounodiffussion (SRID). RESULTS: The results indicated that 32% of the dairy products were contaminated by S. aureus (cream 18%, cheese 10%, milk 4%). The PCR results showed that 15.6% of the S. aureus isolates possessed the SEA gene, 9.3% had the SEB gene, and 6.2% possessed both genes. The evaluation of enterotoxin production indicated that 80% of SEA and 33% of SEB genes were expressed. CONCLUSION: Enterotoxins SEA and SEB are heat stable and consequently; heating has no effect on dairy products contaminated by entertoxins. Subsequently, gastritis may occur within several hours after consumption. Our findings suggest that PCR is a rapid, sensitive, specific, and inexpensive method for detecting SE and can replace the traditional assays.

Using array-comparative genomic hybridization to define molecular portraits of primary breast cancers.

We analysed 148 primary breast cancers using BAC-arrays containing 287 clones representing cancer-related gene/loci to obtain genomic molecular portraits. Gains were detected in 136 tumors (91.9%) and losses in 123 tumors (83.1%). Eight tumors (5.4%) did not have any genomic aberrations in the 281 clones analysed. Common (more than 15% of the samples) gains were observed at 8q11-qtel, 1q21-qtel, 17q11-q12 and 11q13, whereas common losses were observed at 16q12-qtel, 11ptel-p15.5, 1p36-ptel, 17p11.2-p12 and 8ptel-p22. Patients with tumors registering either less than 5% (median value) or less than 11% (third quartile) total copy number changes had a better overall survival (log-rank test: P=0.0417 and P=0.0375, respectively). Unsupervised hierarchical clustering based on copy number changes identified four clusters. Women with tumors from the cluster with amplification of three regions containing known breast oncogenes (11q13, 17q12 and 20q13) had a worse prognosis. The good prognosis group (Nottingham Prognostic Index (NPI)

A gene-expression signature to predict survival in breast cancer across independent data sets.

Prognostic signatures in breast cancer derived from microarray expression profiling have been reported by two independent groups. These signatures, however, have not been validated in external studies, making clinical application problematic. We performed microarray expression profiling of 135 early-stage tumors, from a cohort representative of the demographics of breast cancer. Using a recently proposed semisupervised method, we identified a prognostic signature of 70 genes that significantly correlated with survival (hazard ratio (HR): 5.97, 95% confidence interval: 3.0-11.9, P = 2.7e-07). In multivariate analysis, the signature performed independently of other standard prognostic classifiers such as the Nottingham Prognostic Index and the 'Adjuvant!' software. Using two different prognostic classification schemes and measures, nearest centroid (HR) and risk ordering (D-index), the 70-gene classifier was also found to be prognostic in two independent external data sets. Overall, the 70-gene set was prognostic in our study and the two external studies which collectively include 715 patients. In contrast, we found that the two previously described prognostic gene sets performed less optimally in external validation. Finally, a common prognostic module of 29 genes that associated with survival in both our cohort and the two external data sets was identified. In spite of these results, further studies that profile larger cohorts using a single microarray platform, will be needed before prospective clinical use of molecular classifiers can be contemplated.

Endocrine profiles and semen quality in spinal cord injured men.

PURPOSE: To evaluate the hypothalamic-pituitary-testis (HPT) axis, endocrine profiles and semen quality in men with spinal cord injury (SCI). MATERIALS AND METHODS: Fifty-five men with SCI were studied. Serum levels of FSH, LH, testosterone, oestradiol and prolactin (PRL) were determined; the LH-releasing hormone (LHRH) stimulation test and a semen analysis were performed, and testicular volumes were measured. Thirty-six age-matched healthy male volunteers and 34 noninjured infertile men served as controls. RESULTS: Eight SCI subjects had low basal LH, four had low basal FSH, and 16 had decreased basal serum levels of LH and FSH. Of subjects with lower serum levels of gonadotrophins (LH and/or FSH), nine had low serum testosterone and seven had hyperprolactinaemia. Serum levels of oestradiol were similar for all groups. There were increased LH and FSH responses to LHRH in SCI subjects compared to normal controls, but this difference was only statistically significant in SCI subjects with lower than normal serum levels of LH and/or FSH. There was no significant difference in testis volume between SCI subjects and controls. The mean semen volume in SCI subjects was lower than from controls, but the difference was not statistically significant. Sperm motility and percent normal sperm morphology were lower in SCI compared to normal controls but not to infertile control subjects. In total, 51% and 86% of SCI subjects had at least one hormonal or axis abnormality, respectively. CONCLUSION: We conclude that hypogonadotropism in SCI subjects is likely to be secondary to altered neural or hormonal pathways between the hypothalamus and the pituitary gland, and that these endocrine abnormalities may be the mechanisms contributing to impairment of semen quality.

Eyelid reconstruction: an oculoplastic surgeon's perspective.

The eyelids provide structural support for the globe and play an essential role in protecting and lubricating the eye. Trauma, tumor resection, or congenital defects may compromise eyelid function. The goals of eyelid reconstruction are to restore the function of the eyelids and lacrimal drainage apparatus, provide adequate protection for the globe, and achieve reasonable cosmetic results.

Statistical inference from multiply censored environmental data.

Maximum likelihood estimation for multiply censored samples are discussed. Approximate confidence intervals for the lognormal mean are obtained using both Taylor expansion method and direct method. It is shown that the direct method performs noticeably better than the Taylor expansion method. Simulation results and applications are provided.