Sexual dimorphism in a neuronal mechanism of spinal hyperexcitability across rodent and human models of pathological pain.

The prevalence and severity of many chronic pain syndromes differ across sex, and recent studies have identified differences in immune signalling within spinal nociceptive circuits as a potential mediator. Although it has been proposed that sex-specific pain mechanisms converge once they reach neurons within the superficial dorsal horn, direct investigations using rodent and human preclinical pain models have been lacking. Here, we discovered that in the Freund's adjuvant in vivo model of inflammatory pain, where both male and female rats display tactile allodynia, a pathological coupling between KCC2-dependent disinhibition and N-methyl-D-aspartate receptor (NMDAR) potentiation within superficial dorsal horn neurons was observed in male but not female rats. Unlike males, the neuroimmune mediator brain-derived neurotrophic factor (BDNF) failed to downregulate inhibitory signalling elements (KCC2 and STEP61) and upregulate excitatory elements (pFyn, GluN2B and pGluN2B) in female rats, resulting in no effect of ex vivo brain-derived neurotrophic factor on synaptic NMDAR responses in female lamina I neurons. Importantly, this sex difference in spinal pain processing was conserved from rodents to humans. As in rodents, ex vivo spinal treatment with BDNF downregulated markers of disinhibition and upregulated markers of facilitated excitation in superficial dorsal horn neurons from male but not female human organ donors. Ovariectomy in female rats recapitulated the male pathological pain neuronal phenotype, with BDNF driving a coupling between disinhibition and NMDAR potentiation in adult lamina I neurons following the prepubescent elimination of sex hormones in females. This discovery of sexual dimorphism in a central neuronal mechanism of chronic pain across species provides a foundational step towards a better understanding and treatment for pain in both sexes.

An antibacterial T6SS in Pantoea agglomerans pv. betae delivers a lysozyme-like effector to antagonize competitors.

The type VI secretion system (T6SS) is deployed by numerous Gram-negative bacteria to deliver toxic effectors into neighbouring cells. The genome of Pantoea agglomerans pv. betae (Pab) phytopathogenic bacteria contains a gene cluster (T6SS1) predicted to encode a complete T6SS. Using secretion and competition assays, we found that T6SS1 in Pab is a functional antibacterial system that allows this pathogen to outcompete rival plant-associated bacteria found in its natural environment. Computational analysis of the T6SS1 gene cluster revealed that antibacterial effector and immunity proteins are encoded within three genomic islands that also harbour arrays of orphan immunity genes or toxin and immunity cassettes. Functional analyses indicated that VgrG, a specialized antibacterial effector, contains a C-terminal catalytically active glucosaminidase domain that is used to degrade prey peptidoglycan. Moreover, we confirmed that a bicistronic unit at the end of the T6SS1 cluster encodes a novel antibacterial T6SS effector and immunity pair. Together, these results demonstrate that Pab T6SS1 is an antibacterial system delivering a lysozyme-like effector to eliminate competitors, and indicate that this bacterium contains additional novel T6SS effectors.

Loss of STEP61 couples disinhibition to N-methyl-d-aspartate receptor potentiation in rodent and human spinal pain processing.

Dysregulated excitability within the spinal dorsal horn is a critical mediator of chronic pain. In the rodent nerve injury model of neuropathic pain, BDNF-mediated loss of inhibition (disinhibition) gates the potentiation of excitatory GluN2B N-methyl-d-aspartate receptor (NMDAR) responses at lamina I dorsal horn synapses. However, the centrality of this mechanism across pain states and species, as well as the molecular linker involved, remain unknown. Here, we show that KCC2-dependent disinhibition is coupled to increased GluN2B-mediated synaptic NMDAR responses in a rodent model of inflammatory pain, with an associated downregulation of the tyrosine phosphatase STEP61. The decreased activity of STEP61 is both necessary and sufficient to prime subsequent phosphorylation and potentiation of GluN2B NMDAR by BDNF at lamina I synapses. Blocking disinhibition reversed the downregulation of STEP61 as well as inflammation-mediated behavioural hypersensitivity. For the first time, we characterize GluN2B-mediated NMDAR responses at human lamina I synapses and show that a human ex vivo BDNF model of pathological pain processing downregulates KCC2 and STEP61 and upregulates phosphorylated GluN2B at dorsal horn synapses. Our results demonstrate that STEP61 is the molecular brake that is lost following KCC2-dependent disinhibition and that the decrease in STEP61 activity drives the potentiation of excitatory GluN2B NMDAR responses in rodent and human models of pathological pain. The ex vivo human BDNF model may thus form a translational bridge between rodents and humans for identification and validation of novel molecular pain targets.

The Effect of Obesity on the Quality of Bowel Preparation for Colonoscopy: Results From a Large Observational Study.

BACKGROUND: Obesity has been linked to suboptimal bowel preparation but this association has not been conclusively investigated in prospective studies. GOALS: Our objective was to determine whether any relationship exists between obesity as measured by body mass index (BMI) and quality of bowel preparation. STUDY: Adult patients who presented for outpatient colonoscopy at a single urban ambulatory surgery center within a 6-month period and fulfilled inclusion criteria were prospectively enrolled for the study. Patients were divided by BMI into subcategories based on the World Health Organization international classification of obesity. The Modified Aronchick scale was used to assess bowel preparation for colonoscopy. A univariate and multivariate analysis was used to determine a possible association between BMI and poor preparation. RESULTS: A total of 1429 patients were evaluated. On the basis of inclusion criteria, 1314 subjects were analyzed, out of which 73% were overweight or obese. Inadequate bowel preparation was noted in 21.1% of patients. There was no correlation between obesity and the quality of the bowel preparation. Male gender (P=0.002), diabetes mellitus (P<0.0001), liver cirrhosis (P=0.001), coronary artery disease (P=0.003), refractory constipation (P<0.0001), and current smoking (P=0.01) were found to be independently predictive of poor bowel preparation. CONCLUSIONS: Increased BMI is not predictive of suboptimal bowel preparation for colonoscopy. The results of our study are pivotal given the increased risk of colorectal cancer in obese patients and their known lower rate of colorectal cancer screening in certain populations. It is important to avoid subjecting these patients to an intensive bowel preparation that may further discourage screening in a patient population that requires it.

Kissing dentigerous cysts involving mandibular canines: report of unusual case with review of literature.

Dentigerous cysts are odontogenic developmental cysts, which mostly surround the crown of unerupted teeth, odontomas or supernumerary teeth. These cysts are mostly solitary in occurrence and their bilateral presentation is rare, especially in the absence of syndromes such as Maroteaux-Lamy, basal cell nevus or cleidocranial dysplasia. We present an unusual case of a 24-year-old female with nonsyndromic bilateral dentigerous cysts associated with unerupted mandibular canines that were diagnosed histopathologically as dentigerous cysts.

Prospective Observational Evaluation of the Time-Dependency of Adalimumab Immunogenicity and Drug Concentration in Ulcerative Colitis Patients: the POETIC II Study.

BACKGROUND AND AIMS: Home self-injection of the human anti-tumour necrosis alpha [anti-TNFα] monoclonal adalimumab complicates prospective serial-sampling studies. Although a recent study examined adalimumab levels and immunogenicity in Crohn's disease [CD] patients, prospective real-world data from ulcerative colitis [UC] patients are lacking. METHODS: A three-monthly home-visit programme from induction was established prospectively for UC patients. Clinical scores were determined at each visit, and sera were obtained for assessment of drug and anti-adalimumab antibody levels. Calprotectin was measured using a smartphone-based app. This cohort was compared to a parallel prospective cohort of adalimumab-treated CD patients [POETIC1]. RESULTS: Fifty UC patients starting adalimumab [median follow-up 28 weeks] were compared to 98 adalimumab-treated CD patients [median follow-up 44 weeks]. Only 11/50 UC patients [22%] continued treatment to the end of the follow-up compared with 50/98 [51%] CD patients (odds ratio [OR] = 0.27, p = 0.001). Loss of response was significantly more common in UC patients [OR = 3.2, p = 0.001]. Seventeen patients [34%] in the UC cohort developed anti-adalimumab antibodies, 9/17 [52.9%] as early as week 2. There was no difference between patient cohorts in the overall development of anti-adalimumab antibodies [34% vs 30.6%, respectively, OR = 1.67, p = 0.67], nor was there a difference in early immunogenicity [OR = 1.39, p = 0.35]. There was no difference in low drug levels [<3 µg/mL] between the two cohorts [OR = 0.87, p = 0.83]. CONCLUSIONS: Loss of response to adalimumab therapy was significantly more common in the UC compared to the CD cohort and was driven by a higher rate of non-immunogenic, pharmacodynamic parameters.

Silver-coated nylon dressing plus active DC microcurrent for healing of autogenous skin donor sites.

INTRODUCTION: Burn wounds are a significant cause of morbidity and mortality, and improved outcomes are demonstrated with early closure of both primary burn wounds and skin donor sites. Thus, technology that decreases the healing time of burns and donor sites would be potentially lifesaving. We present the results of a single-center, prospective, double-blinded, randomized controlled trial to evaluate the efficacy of silver-coated dressing with active microcurrent in comparison to silver-coated dressing with sham microcurrent on wound-closure time for autogenous skin donor sites. METHODS: Four hundred five patients were screened for treatment of their donor sites using a silver-coated nylon dressing with either sham or active microcurrent stimulation. Thirty patients were enrolled in the study and then randomized. Of these, 5 patients were removed from analysis due to protocol deviations. Differences in time-to-closure were analyzed using Kaplan-Meier analysis and the proportional hazard regression model. Subjective verbal pain rating scores (0-10; 0, no pain; 10, worst pain) were also recorded. All devices were blinded and programmed at an outside facility, so that every patient had either an active or sham device. The study was unblinded only after the final patient's donor site had healed. All patients achieved donor-site healing before postoperative day 20. The 14 patients in the active microcurrent group [mean, 10.8 (2.9) days; range, 7-15 days] experienced no difference in time to wound healing as compared to the remaining patients in the sham microcurrent group [mean, 11.1 (2.0) days; range, 8-14 days; P = 0.75]. There were no differences in pain from one group compared to the other. None of the donor sites exhibited clinical signs of infection. CONCLUSIONS: In a sample size of 25 burn patients, the addition of direct microcurrent to silver-nylon dressings did not decrease time to wound closure of skin donor sites, and it did not show a difference in reported pain levels.

A Vibrio T6SS-Mediated Lethality in an Aquatic Animal Model.

Bacteria belonging to the genus Vibrio include many known and emerging pathogens. Horizontal gene transfer of pathogenicity islands is a major contributor to the emergence of new pathogenic Vibrio strains. Here, we use the brine shrimp Artemia salina as a model and show that the marine bacterium Vibrio proteolyticus uses a horizontally shared type VI secretion system, T6SS3, to intoxicate a eukaryotic host. Two T6SS3 effectors, which were previously shown to induce inflammasome-mediated pyroptotic cell death in mammalian phagocytic cells, contribute to this toxicity. Furthermore, we find a novel T6SS3 effector that also contributes to the lethality mediated by this system against Artemia salina. Therefore, our results reveal a T6SS that is shared among diverse vibrios and mediates host lethality, indicating that it can lead to the emergence of new pathogenic strains. IMPORTANCE The rise in sea surface temperature has been linked to the spread of bacteria belonging to the genus Vibrio and the human illnesses associated with them. Since vibrios often share virulence traits horizontally, a better understanding of their virulence potential and determinants can prepare us for new emerging pathogens. In this work, we showed that a toxin delivery system found in various vibrios mediates lethality in an aquatic animal. Taken together with previous reports showing that the same system induces inflammasome-mediated cell death in mammalian phagocytic cells, our findings suggest that this delivery system and its associated toxins may contribute to the emergence of pathogenic strains.

Beyond Medical Care: How Different National Models of Care Impact the Experience of Adolescent and Young Adult Cancer Patients.

Patient experience is positively associated with clinical effectiveness, quality care, and patient safety. This study examines the experience of care of adolescents and young adult (AYA) cancer patients from Australia and the United States, allowing a comparison of patient experiences in the context of different national models of cancer care delivery. Participants (n = 190) were aged 15-29 years and received cancer treatment from 2014 to 2019. Australians (n = 118) were recruited nationally by health care professionals. U.S. participants (n = 72) were recruited nationally via social media. The survey included demographic and disease variables, and questions regarding medical treatment, information and support provision, care coordination, and satisfaction across the treatment pathway. Sensitivity analyses examined the possible contribution of age and gender. Most patients from both countries were satisfied or very satisfied with their medical treatment (chemotherapy, radiotherapy, and surgery). There were significant differences between countries in the provision of fertility preservation services, age-appropriate communication, and psychosocial support. Our findings suggest when a national system of oversight with both state and federal funding is implemented, as is the case in Australia but not in the United States, significantly more AYAs with cancer receive age-appropriate information and support services, and improved access to specialist services such as fertility care. A national approach with government funding and centralized accountability appears to be associated with substantial benefits for the well-being of AYAs undergoing cancer treatment.

Salivary detection of high-risk human papillomavirus 16 in oral squamous cell carcinoma using polymerase chain reaction in the South Indian population.

INTRODUCTION: Human papilloma virus (HPV) has been associated with oral squamous cell carcinoma (OSCC) as a potential carcinogen. There are several types of HPV, of which type 16 has been strongly implicated in carcinogenesis. HPV16 in saliva can potentially facilitate early detection of subclinical cases that may warrant further diagnosis, monitoring and intervention. AIM: The aim of this study was to evaluate the presence of HPV 16 in saliva and lesional tissue of OSCC and to determine the use of saliva as an alternative non invasive diagnostic tool in HPV16 identification. MATERIALS AND METHODS: 30 cases of Histopathologically confirmed OSCC with HPV positive on ELISA were taken up for the study. The tumour tissue and saliva sample of each patient were obtained to detect the presence of specific HPV16 genotype by polymerase chain reaction (PCR). The data was subjected to statistical analysis using Student t-test. RESULTS: In our study we found 28/30, 26/30 positive for HPV 16 in tissue and saliva samples respectively on PCR analysis. The P value was statistically significant (0.00). CONCLUSION: The study revealed significant prevalence of HPV 16 among both tissue and salivary specimens of OSCC patients in south Indian population. Though, the yielded content was relatively less in saliva, it can be concluded that, saliva being a non invasive tool proved to be as useful as tissue specimen and can be used as an alternative indicator of HPV16 positivity in OSCC.

A comparative genomics methodology reveals a widespread family of membrane-disrupting T6SS effectors.

Gram-negative bacteria deliver effectors via the type VI secretion system (T6SS) to outcompete their rivals. Each bacterial strain carries a different arsenal of effectors; the identities of many remain unknown. Here, we present an approach to identify T6SS effectors encoded in bacterial genomes of interest, without prior knowledge of the effectors' domain content or genetic neighborhood. Our pipeline comprises a comparative genomics analysis followed by screening using a surrogate T6SS+ strain. Using this approach, we identify an antibacterial effector belonging to the T6SS1 of Vibrio parahaemolyticus, representing a widespread family of T6SS effectors sharing a C-terminal domain that we name Tme (Type VI membrane-disrupting effector). Tme effectors function in the periplasm where they intoxicate bacteria by disrupting membrane integrity. We believe our approach can be scaled up to identify additional T6SS effectors in various bacterial genera.

A modular effector with a DNase domain and a marker for T6SS substrates.

Bacteria deliver toxic effectors via type VI secretion systems (T6SSs) to dominate competitors, but the identity and function of many effectors remain unknown. Here we identify a Vibrio antibacterial T6SS effector that contains a previously undescribed, widespread DNase toxin domain that we call PoNe (Polymorphic Nuclease effector). PoNe belongs to a diverse superfamily of PD-(D/E)xK phosphodiesterases, and is associated with several toxin delivery systems including type V, type VI, and type VII. PoNe toxicity is antagonized by cognate immunity proteins (PoNi) containing DUF1911 and DUF1910 domains. In addition to PoNe, the effector contains a domain of unknown function (FIX domain) that is also found N-terminal to known toxin domains and is genetically and functionally linked to T6SS. FIX sequences can be used to identify T6SS effector candidates with potentially novel toxin domains. Our findings underline the modular nature of bacterial effectors harboring delivery or marker domains, specific to a secretion system, fused to interchangeable toxins.

NAD+ improves neuromuscular development in a zebrafish model of FKRP-associated dystroglycanopathy.

BACKGROUND: Secondary dystroglycanopathies are muscular dystrophies that result from mutations in genes that participate in Dystroglycan glycosylation. Glycosylation of Dystroglycan is essential for muscle fibers to adhere to the muscle extracellular matrix (myomatrix). Although the myomatrix is disrupted in a number of secondary dystroglycanopathies, it is unknown whether improving the myomatrix is beneficial for these conditions. We previously determined that either NAD+ supplementation or overexpression of Paxillin are sufficient to improve muscle structure and the myomatrix in a zebrafish model of primary dystroglycanopathy. Here, we investigate how these modulations affect neuromuscular phenotypes in zebrafish fukutin-related protein (fkrp) morphants modeling FKRP-associated secondary dystroglycanopathy. RESULTS: We found that NAD+ supplementation prior to muscle development improved muscle structure, myotendinous junction structure, and muscle function in fkrp morphants. However, Paxillin overexpression did not improve any of these parameters in fkrp morphants. As movement also requires neuromuscular junction formation, we examined early neuromuscular junction development in fkrp morphants. The length of neuromuscular junctions was disrupted in fkrp morphants. NAD+ supplementation prior to neuromuscular junction development improved length. We investigated NMJ formation in dystroglycan (dag1) morphants and found that although NMJ morphology is disrupted in dag1 morphants, NAD+ is not sufficient to improve NMJ morphology in dag1 morphants. Ubiquitous overexpression of Fkrp rescued the fkrp morphant phenotype but muscle-specific overexpression only improved myotendinous junction structure. CONCLUSIONS: These data indicate that Fkrp plays an early and essential role in muscle, myotendinous junction, and neuromuscular junction development. These data also indicate that, at least in the zebrafish model, FKRP-associated dystroglycanopathy does not exactly phenocopy DG-deficiency. Paxillin overexpression improves muscle structure in dag1 morphants but not fkrp morphants. In contrast, NAD+ supplementation improves NMJ morphology in fkrp morphants but not dag1 morphants. Finally, these data show that muscle-specific expression of Fkrp is insufficient to rescue muscle development and homeostasis.

Insulin sensitivity and cardiac autonomic function in young male practitioners of yoga.

BACKGROUND: While yoga is thought to reduce the risk of chronic non-communicable diseases such as diabetes, there are no studies on insulin sensitivity in long term practitioners of yoga. We assessed insulin sensitivity and cardiac autonomic function in long term practitioners of yoga. METHODS: Fifteen healthy, young, male practitioners of yoga were compared with 15 young, healthy males who did not practice yoga matched for body-mass index. Fasting insulin sensitivity was measured in the fasting state by the hyperinsulinaemic-euglycaemic clamp. RESULTS: There were no significant differences between the groups in their anthropometry or body composition. However, the fasting plasma insulin was significantly lower in the yoga group. The yoga group was also more insulin sensitive (yoga 7.82 [2.29] v. control 4.86 [11.97] (mg/[kg.min])/(microU/ml), p < 0.001). While the body weight and waist circumference were negatively correlated with glucose disposal rate in the controls, there were no similar correlations in the yoga group. The yoga group had significantly higher low-frequency power and lower normalized high-frequency power. CONCLUSION: Long term yoga practice (for 1 year or more) is associated with increased insulin sensitivity and attenuates the negative relationship between body weight or waist circumference and insulin sensitivity.

The effect of long term combined yoga practice on the basal metabolic rate of healthy adults.

BACKGROUND: Different procedures practiced in yoga have stimulatory or inhibitory effects on the basal metabolic rate when studied acutely. In daily life however, these procedures are usually practiced in combination. The purpose of the present study was to investigate the net change in the basal metabolic rate (BMR) of individuals actively engaging in a combination of yoga practices (asana or yogic postures, meditation and pranayama or breathing exercises) for a minimum period of six months, at a residential yoga education and research center at Bangalore. METHODS: The measured BMR of individuals practicing yoga through a combination of practices was compared with that of control subjects who did not practice yoga but led similar lifestyles. RESULTS: The BMR of the yoga practitioners was significantly lower than that of the non-yoga group, and was lower by about 13 % when adjusted for body weight (P < 0.001). This difference persisted when the groups were stratified by gender; however, the difference in BMR adjusted for body weight was greater in women than men (about 8 and 18% respectively). In addition, the mean BMR of the yoga group was significantly lower than their predicted values, while the mean BMR of non-yoga group was comparable with their predicted values derived from 1985 WHO/FAO/UNU predictive equations. CONCLUSION: This study shows that there is a significantly reduced BMR, probably linked to reduced arousal, with the long term practice of yoga using a combination of stimulatory and inhibitory yogic practices.

Sexual dimorphism in foramen magnum dimensions in the South Indian population: A digital submentovertex radiographic study.

PURPOSE OF THE STUDY: Personal identification is a vital arena of forensic investigation, facilitating the search for missing persons. This process of identification is eased by the determination of age, sex, and ethnicity. In situations where there are fragmented and mutilated skeletal remains, sex determination is relatively difficult, and it becomes important to establish the accuracy of individual bones. AIM: This study aims to evaluate sexual dimorphism in foramen magnum (FM) dimensions in the South Indian population using digital submentovertex (SMV) radiograph. MATERIALS AND METHODS: 150 individuals (75 males and 75 females) were subjected to digital SMV radiography. FM in the resultant image was assessed for longitudinal and transverse diameters, circumference, and area. Also, one particular shape was assigned to each image based on the classification of Chethan et al. of FM shapes. Three qualified oral radiologists performed all the measurements twice within an interval of 10 days. RESULTS AND CONCLUSION: The values obtained for all four parameters were statistically significant and higher in males than in females. The most common morphology of FM was an egg shape while hexagonal was the least common morphology. Circumference was the best indicator of sex followed by area, transverse diameter, and longitudinal diameter. Having achieved a high accuracy of 67.3% with digital SMV radiograph makes it a reliable and reproducible alternative to dry skulls for sex determination.

Effects of histamine and related compounds on the release of immunoreactive thyrotropin-releasing hormone from the rat stomach in vitro.

Effects of histamine and related compounds on the release of immunoreactive thyrotropin-releasing hormone (ir-TRH) from the rat stomach in vitro were studied. The rat stomach was incubated in medium 199 with 1.0 mg/ml of bacitracin and 100 micrograms/ml of ascorbic acid (pH 7.4) for 20 min. The amount of TRH release into the medium was measured by radioimmunoassay. The ir-TRH release from the rat stomach was enhanced significantly in a dose-related manner with the addition of histamine and inhibited with the addition of famotidine, but not with mepyramine. The stimulatory effect of histamine on ir-TRH release from the stomach was partially blocked with the addition of famotidine, but not with mepyramine. The elution profile of acid-methanol-extracted rat stomach on Sephadex G-10 was identical to that of synthetic TRH. These findings suggest that histamine stimulated ir-TRH release from the rat stomach in vitro, and that histamine's effects may be mediated via a H2-receptor.

Peripheral administration of eel calcitonin inhibits thyrotropin secretion in rats.

The effects of peripheral administration of eel calcitonin on thyrotropin (TSH) and thyrotropin-releasing hormone (TRH) secretion were studied in rats. Eel calcitonin (50 U/kg) was injected i.v. The hypothalamic immunoreactive TRH (ir-TRH) contents increased significantly after calcitonin injection. Plasma TSH levels decreased in a dose-related manner with a nadir at 30 min after the injection. The plasma ir-TRH and TSH responses to cold as well as the plasma TSH response to TRH were inhibited by calcitonin. The inhibitory effect of calcitonin on TSH levels was prevented in the haloperidol-, pimozide- or p-chlorophenylalanine-pretreated group, but not in the L-DOPA- or 5-hydroxytryptophan-pretreated group. The findings suggest that calcitonin acts on both the hypothalamus and the pituitary to inhibit TRH and TSH release, and that its effects may be modified by amines of the central nervous system.

National survey of blindness and low vision in Lebanon.

AIMS: To survey level of blindness and low vision in Lebanon. METHODS: A population survey was undertaken in 10,148 individuals to measure the prevalence and identify the causes of blindness in Lebanon. RESULTS: The prevalence of blindness was 0.6% and that of low vision 3.9%. The major causes of blindness were cataract (41.3%) and uncorrected large refractive error (12.6%). CONCLUSION: Most causes of blindness in Lebanon can be controlled by various educational and medical programmes.

The impact of war on the physical and mental health of the family: the Lebanese experience.

This paper addresses the impact of war-related stressful life events on the health of families living through the war conditions prevailing in Lebanon for the past 12 years. Health outcome is represented by indicators of somatization, depression, psychological symptoms, interpersonal relations and marital relations. Associations are described between elements of war stress and the health outcome variables for mothers, fathers and adolescents in a sample of Beirut families. The role of the mediating factors of social support and social class is also discussed.