[COVID-19 Pandemic: Psychosocial impact among healthcare professionals in Tunisia]. / Pandémie COVID-19 : impact psychosocial sur le personnel de santé en Tunisie.

OBJECTIVE: To determine the psycho-affective impact of the Covid-19 pandemic on the mental health of health professionals in Tunisia and to estimate the associated factors. METHODS: This is a multicenter, cross-sectional, descriptive and analytical study of health professionals carried out from May 2, 2020 to June 30, 2020 in Tunisia. Healthcare professionals included doctors, nurses, dentists and pharmacists. The participants answered a pre-established questionnaire using an electronic "Google Form". This questionnaire gathered demographic data and medical history. It included two psychometric scales, the GAD-7 (General Anxiety Disorder-7) and the PHQ-9 (Patient Health Questionnaire-9) to assess the prevalence and intensity of anxiety symptoms and depressive symptoms respectively. RESULTS: The study included 203 healthcare professionals. The professionals had a mean age of 30.74±6.33years, 69.5 % were women, and the majority were doctors (77.8 %). Among professionals, 9.4 % were nurses, 7.4 % were dentists, and 5.4 % were pharmacists. A third of the participants 34.3 % worked in departments with Covid-19 patienfor having moderate to severe anxiety symptoms. CONCLUSION: In order to ensure better patient care, early detection of psychiatric disorders and the implementation of specific strategies to ensure better mental health among healthcare professionals are priorities not only during the current pandemic but also in the event of a future similar pandemic.

Effect of COVID-19 on mental health among the young population in Lebanon.

BACKGROUND: COVID-19 is a global pandemic that has raised worldwide public health concerns. The wide spread of the virus has led to unprecedented disturbance to regular life for people around the globe and impacted their mental health. AIMS: The aims of the current study were to investigate the prevalence of psychiatric symptoms related to insomnia, depression, and anxiety, and identify risk factors contributing to psychological stress in Lebanese young population during COVID-19 pandemic. METHOD: A cross-sectional study was done on the Lebanese young population. Participants were 4397 males and females aged 18 to 35 years who filled a self-administered online questionnaire. Three validated scales were used to measure the mental health status of the participants during the COVID-19 pandemic: 7-item Insomnia Severity Index for insomnia, the Patient Health Questionnaire 9-item depression module for depression, and the 7-item Generalized Anxiety Disorder scale for anxiety. RESULTS: The median interquartile range scores for anxiety, insomnia, and depression, were 8 (4-13), 10 (5-14), and 9 (5-12) respectively. Higher anxiety scores were reported with female gender (P<0.001) and alcohol usage (P=0.04). Moderate to severe insomnia was associated with single (P=0.02) and divorced marital status (P=0.003), university education (P<0.001), consumption of caffeinated beverages (P=0.02) and energy drinks (P=0.03). Higher depression scores were associated with status of being the only person working at home (P=0.01), family income more than 500 USD (P=0.008), multiple insurance plans (P=0.01), and contact with a confirmed COVID-19 case (P=0.01). CONCLUSIONS: The findings of this study demonstrate the considerable impact of COVID-19 pandemic and lockdown on Lebanese young population's mental status such as anxiety, depression and insomnia. Further follow-up studies are warranted to assess the long-term mental effects that can be imposed by the pandemic.

Cross-talk between apelin and vasopressin in response to different osmotic stimuli in type 2 diabetic rats.

Apelin, a peptide hormone that has been linked to insulin resistance, obesity and glucose metabolism, coexists with arginine vasopressin (AVP) in hypothalamic magnocellular neurons that control body fluid homeostasis. The significant correlation between serum glucose and serum osmolarity in uncontrolled DM indicates the need for adequate compensation, but how apelin and AVP contribute to this is still unsettled. This study aims to investigate the interaction between apelin and AVP in osmotic regulation in type 2 diabetes mellitus (T2DM), and to explore the underlying mechanism. Forty-eight adult male albino rats were divided into six groups: control (isotonic, ip 0.9% NaCl; hypotonic, ip distilled water; hypertonic, ip 2% NaCl) groups and T2DM (isotonic, hypotonic, hypertonic) groups. Serum levels of AVP, apelin, Na, glucose, serum and urine osmolarity were measured; kidney samples were taken for Aquaporin 2 channels (AQP2) and epithelial sodium channel gamma subunit (ENaCγ) gene expression. Hypothalamic tissue sections were used for immunohistochemical staining of apelin and AVP. Both in control and diabetic groups serum apelin, showed a significant negative correlation with serum AVP (r=-0.533, p≤ 0.001). Serum apelin and AVP were inversely proportional to their hypothalamic protein expression. Serum apelin and AVP were significantly higher in diabetic rats (P= 0.001) yet their percentage change in response to hypo and hyper-osmotic stimuli (1.5±0.7, -0.34±0.15 and -0.38±0.13, 1.95±0.36, respectively) was less pronounced when compared to control rats (3.28±0.52, -0.59±0.12 and -0.45±0.13, 2.58±0.93, respectively). Na and ENaCγ levels significantly increased in hypertonic rats, while AQP2 gene expression significantly increased in hypotonic rats. Both apelin and AVP reacted to osmotic stimuli in T2DM but with less sensitivity than in control rats. In spite of its abnormal increased levels in diabetic rats, apelin maintained its role through counteracting AVP action.

Schizophrenia-Like Psychotic Symptoms Associated to Leigh Syndrome.

Introduction: Leigh syndrome (LS) is a mitochondrial disease characterized by subacute necrotizing encephalomyelopathy with an estimated incidence of 1:40,000 births. The comorbidity of psychotic symptoms noted in mitochondrial and psychiatric diseases has spurred interest in the effects of DNA mutations and psychiatric disorders. Case presentation. We report the case of a Tunisian 28-year-old male diagnosed with maternally inherited Leigh syndrome. He presented anxiety and auditory hallucinations, and he reported a vague, unsystematized delusion evolving since 6 months. Significant remission was observed at risperidone 3 mg/day. Discussion. The normality of explorations in our case raised the issue of the link between the two diseases, supporting the hypothesis that mitochondrial dysfunction maybe the primary origin of psychotic disorders. Conclusion: The aim of our work is to study the relations between mitochondrial dysfunction and psychiatric symptoms. Further study of mitochondrial dysfunction in psychiatric disorders is expected to be useful for the development of cellular disease markers and new psychotropics.

Synthesis of 2D Metal-Organic Nanosheets (MONs) by Liquid Phase Exfoliation: Applications in Effective Delivery of Antiulcer Drugs and Selective Adsorption and Removal of Cationic Dyes.

Nowadays, the fabrication of 2D metal-organic nanosheets (2D MONs) has entered the research arena fascinating researchers worldwide. However, a lack of efficient and facile methods has remained a bottleneck for the manufacturing of these 2D MONs. Herein, a 2D metal-organic framework (MOF), i.e., 2D Cu-MOF, was synthesized using a facile and convenient stirring method by using 4,4'-trimethylenedipyridine (TMDP) as an organic linker. The as-prepared MOF was characterized in detail and based on single crystal X-ray diffraction analysis, it was established that tangled layers in the 2D Cu-MOF are interconnected to produce thick strands. These tangled layers could be easily separated via ultrasonication-induced liquid phase exfoliation (UILPE) to give the 2D Cu-MON as illustrated through Tyndall light scattering and exhaustive microscopic exploration such as scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The application of this 2D Cu-MON was assessed in the field of drug delivery revealing exceptional drug loading for the drug lansoprazole (LPZ) by 2D Cu-MONs as well as drug release in the acidic and neutral medium demonstrating that the 2D Cu-MON is an excellent carrier for antiulcer drug delivery. For environmental protection, the application of 2D Cu-MON was also examined toward the removal of various cationic and anionic dyes with excellent selectivity toward cationic dye removal. The plausible mechanism for dye removal indicated the involvement of cation-π and π-π interactions, for the effective adsorption of cationic dyes as well as a increase in the surface area of 2D Cu-MON by UILPE. Remarkably, the high drug loading and dye removal are imputed to the increase in surface area by UILPE. In a nutshell, the developed 2D Cu-MON will prove to be beneficial for application in the field of drug delivery as well as for wastewater treatment.

BPA and its analogs increase oxidative stress levels in in vitro cultured granulosa cells by altering anti-oxidant enzymes expression.

Bisphenol A is a widespread endocrine disruptor with numerous effects on reproductive functions. Limitations on BPA in manufacturing has prompted the use of analogs, such as BPS and BPF, with limited research on their safety. The objective of this study was to evaluate the effects of BPA and its analogs on oxidative stress levels within bovine granulosa cells and to measure the expression of key antioxidant genes. Results indicate that BPA and BPF reduce cell viability and induce mitochondrial dysfunction and all three bisphenols increased production of reactive oxygen species as early as 12hrs post exposure. BPA increased the levels of antioxidants at 12hrs at the mRNA and protein levels, while these results were not significant at 48hrs. These results together suggest that BPA and its analogs can induce oxidative stress within bovine granulosa cells, although not necessarily through common mechanisms. Therefore, the use of BPA analogs may have to be re-considered.

The stromal cell-derived factor-1 chemokine is a potent platelet agonist highly expressed in atherosclerotic plaques.

Chemokines are chemotactic cytokines that activate and direct the migration of leukocytes. However, their role in modulating platelet function has not been shown. We studied the direct effect of chemokines on human platelets and found that of the 16 tested only stromal cell-derived factor (SDF)-1 induced platelet aggregation, accompanied by a rise in intracellular calcium. Platelets expressed the SDF-1 receptor, CXCR4, and an antibody to CXCR4 and pertussis toxin inhibited SDF-1-induced platelet aggregation, confirming that this effect is mediated through CXCR4, a Galphai-coupled receptor. SDF-1-induced platelet aggregation was also inhibited by wortmannin, LY294002, and genistein, suggesting that phosphatidylinositol 3-kinase and tyrosine kinase are likely involved in SDF-1-induced platelet aggregation. Because chemokines are produced from multiple vascular cells and atherosclerotic vessels are prone to develop platelet-rich thrombi, we examined the expression of SDF-1 in human atheroma. SDF-1 protein was highly expressed in smooth muscle cells, endothelial cells, and macrophages in human atherosclerotic plaques but not in normal vessels. Our studies demonstrate a direct effect of a chemokine in inducing platelet activation and suggest a role for SDF-1 in the pathogenesis of atherosclerosis and thrombo-occlusive diseases.

[Autoimmune chronic active hepatitis: anatomoclinic's study of 50 patients]. / Les Hépatites auto-immunes (HAI) chroniques de l'adulte: étude anatomoclinique d'une série de 50 patients.

PURPOSE: To analyse anatomoclinic and evolutive aspects of autoimmune hepatitis (AIH) through 50 observations collected in two Internal Medicine departments in Algiers from 1998 to 2002 and to make a review of the literature. METHODS: The study is prospective. The diagnosis of autoimmune hepatitis (AIH) is established according to the recommendations of the score of the International Autoimmune Hepatitis Group (1991) or/and hepatitic damage confirmed by histology. RESULTS: Fifty patients were studied: (32 women-18 men) and the mean age was 38 years (17 to 73). Autoimmune extra-hepatitic manifestations were associated in 26%. The AIH type 1 has been noted in 58%. AIH were type 2 in only 6%. In 22% of the cases AIH were sero-negative and the others AIH represented 14% were classed as overlap-syndrome (5 cases of primary biliary cirrhosis and 2 cases of primary sclerosing cholangitis hepatitis overlap syndrome). The first liver biopsy tissue showed strong necrotic-inflammatory activity in 56% and cirrhosis was identified in 19 patients (38%). The treatment (azathioprine and corticosteroid) was prescribed in 37 patients (74%) in active chronic hepatitis or in compensed cirrhosis. FOLLOW-UP: 28% of the patients died (9-36 months) because cirrhosis's complications or because complications of hepatocarcinoma (3 cases). CONCLUSION: The diagnosis of AIH must be established early for each patient with chronic liver disease particularly is those are supposed as a crypto genetic hepatitis. The prognosis is compromised by delayed diagnosis and the mortality in middle following up is high.

The MHC influences NK and NKT cell functions associated with immune abnormalities and lifespan.

The lifespans of H-2 congenic mice differ significantly. The B10.AKM (H-2m) strain has a median survival time (MST) of 15 months, whereas the B10.BR (H-2k) strain has an MST of 24 months. It was previously shown that B10.AKM mice at 13-15 months of age have immunological function comparable to those of B10.BR mice at 22-26 months of age. These functions include: a low proliferative response, reduced levels of intracellular calcium release [Ca2+]i, and an increase in the frequency of memory helper T-cells (CD4+ CD44hiCD45RBlo). In this report similar deficiencies were demonstrated in B10.AKM mice at 2-4 months of age and show that activated spleen NK1.1+CD4+ T (NKT) cells from young B10.AKM mice produce a significantly higher level of IL-4 but a lower level of IFN-gamma as compared to NKT cells from B10.BR mice of the same age. Also, the cytotoxic activity of natural killer (NK) cells from spleens of young (2-4 months) as well as adult (12-16 months) B10.AKM mice is significantly lower (P < 0.01) than that of NK cells from B10.BR mice. These findings suggest that the NKT activity in young B10.AKM mice is a factor for the early onset of immune dysfunction leading to a shorter lifespan.

Cell-mediated cytotoxicity: a predictor of chronic rejection in pediatric HLA haploidentical renal transplants.

BACKGROUND: Recipient antidonor cytotoxic T-cell activity has been associated with graft loss and acute rejection in renal allograft recipients. The role of immunologic mechanisms in the development of chronic graft rejection is controversial. We analyzed all living related renal transplants performed at Children's Hospital (Boston, MA) from 1983 to 1995 to assess whether cell-mediated cytotoxicity, determined in vitro and measured before transplantation, was predictive of chronic rejection. METHODS: Eighty-three patients were studied retrospectively. Fifty-seven patients with one haplotype-matched renal transplants from living related donors were studied to determine the association between cell-mediated lympholysis (CML) level, acute rejection, chronic rejection, and graft failure. Acute rejection was defined by the decision to treat. Chronic rejection was defined by histology and/or the absolute serum creatinine value using an increasing serum creatinine level >1.0 mg/dl for children less than 3, a creatinine level >1.5 mg/dl for children between 3 and 10 years of age, and a creatinine level >2.0 mg/dl for children above 10 years of age. Return to dialysis or retransplantation was considered graft failure. RESULTS: Of the 57 haploidentical patients, there were 33 males and 24 females. The mean age at transplant was 11.1 years (SD=6.7). Twelve patients developed chronic rejection, 24 patients developed acute rejection, and 7 patients had graft failure. Pretransplant cytotoxic T lymphocyte activity was associated with chronic rejection (P=0.001) and graft failure (P=0.013) but only marginally with acute rejection (P=0.058). Controlling for age and sex, Cox's proportional hazards model revealed that CML level was predictive of time to chronic rejection (P<0.01) but not acute rejection (P=0.11). It was estimated that every 1-unit increase in CML level raises the monthly risk of chronic rejection by 7%. Ten children received HLA-identical kidneys from their siblings. There were no episodes of chronic rejection after 5 years. Two patients with high CML levels had episodes of acute rejection; both patients responded to treatment. CONCLUSION: Our data demonstrate an association between pretransplant cell-mediated cytotoxicity and the occurrence of chronic rejection in living related one-haploidentical renal transplants in pediatric patients.

Non-genomic effects of estrogen and the vessel wall.

Estrogen, like other steroids, is now believed to possess rapid membrane effects independent of the classical gene activation pathway of steroid action. The presence of membrane estrogen receptors has been demonstrated in different cell types, but not yet in vascular tissue. In vivo, estrogen administration rapidly promotes acetylcholine-induced vasodilation of the coronary and peripheral vascular beds of postmenopausal women. Estrogen also causes relaxation of precontracted isolated arterial segments and perfused organ preparations, within minutes of administration of the hormone. These rapid vasomotor effects of estrogen may be related to blockade of the cell membrane voltage-dependent calcium channels, resulting in inhibition of extracellular Ca2+ mobilization and flux. Recently, estradiol has been shown to rapidly affect cyclic nucleotide turnover in vascular segments, smooth muscle, and epithelial cell cultures, suggesting the possibility of a "cross-talk" between membrane-mediated events and nuclear receptor activation.

Mechanism of ethanol-induced aggregation in whole blood.

Effects of ethanol on blood clotting and platelet aggregation have been reported in many models, but its in vitro actions in whole blood, impedance aggregometry have not been reported. We investigated the effect of ethanol in vitro in whole blood and platelet rich plasma of humans and rats, as measured by impedance aggregometry. Ethanol (34 to 170 mM) induced concentration-dependent aggregation in whole blood but not platelet rich plasma. In further studies in rats, aggregation was inhibited by pretreatment of whole blood with the prostacyclin analog iloprost or the enzyme apyrase, which degrades ADP to AMP. Levels of ethanol which produced aggregation in whole blood were also associated with concentration-dependent hemolysis. Based on the requirement for whole blood for ethanol-induced aggregation, the inhibitory effect of apyrase and our observation of hemolysis, and previous studies which have demonstrated the potential contribution of ADP from lysed red blood cells to platelet aggregation, we conclude that ethanol-induced aggregation in whole blood is mediated by erythrocyte lysis and the ADP released from these cells.

The CC chemokines MDC and TARC induce platelet activation via CCR4.

While chemokines have received considerable attention for their role in leukocyte chemotaxis, their effects on platelets have not been well described. We found that two CC chemokine receptor 4 (CCR4) ligands, macrophage-derived chemokine (MDC) and thymus and activation-regulated chemokine (TARC) induce concentration-dependent platelet aggregation and calcium flux. Flow cytometric analysis revealed the expression of CCR4 on platelets and a monoclonal antibody (mAb) to CCR4 inhibited MDC- and TARC-induced platelet aggregation, confirming that this effect is mediated through their common receptor CCR4. MDC fully desensitized TARC-induced calcium mobilization in platelets, while TARC was unable to completely desensitize a subsequent MDC response, which is similar to observations made in Th2 CD4(+) lymphocytes and CCR4-transfected cells. Aspirin (ASA) treatment of platelets allowed reversible primary aggregation but inhibited irreversible complete aggregation, suggesting that MDC- and TARC-induced full platelet aggregation is dependent on cyclooxygenase metabolites of arachidonic acid. MDC and TARC were unable to induce platelet aggregation and platelet secretion in washed human platelets, even though they induced a calcium flux, suggesting that plasma components are required for MDC- and TARC-induced platelet aggregation. Since Th2-type cytokines induce the release of MDC and TARC from cells and the expression of these chemokines is increased in Th2-type inflammation, we hypothesize that MDC and TARC may play a role in platelet activation seen in Th2 diseases, such as asthma and atopic dermatitis.

Inhibition of platelet aggregation in whole blood by alcohol.

Our previous studies have demonstrated that addition of moderate volumes of absolute alcohol (34-170 mM final concentration) to whole blood produces concentration-dependent platelet aggregation, due to release of adenosine diphosphate (ADP) from erythrocytes. We have now investigated the effects of exposure of blood to ethanol by a more "physiologic" protocol, in which 7.8% (w/v) alcohol is added to achieve a final concentration of 1 to 85 mM in human and rat blood or platelet rich plasma (PRP). The effects of short incubation with alcohol on platelet aggregation induced by ADP, collagen and arachidonic acid were examined by the impedance method of aggregometry. Aggregation induced by collagen in PRP of either species was significantly inhibited by 85 mM ethanol, with concentrations as low as 4.25 mM inhibiting the response to collagen in rat whole blood. ADP stimulated only primary, reversible aggregation in rat PRP and whole blood, and these responses were unaffected by alcohol. Human platelets responded to ADP with irreversible aggregation, which was significantly attenuated by 85 mM ethanol in whole blood but not PRP. Arachidonic acid evoked irreversible platelet aggregation in all four preparations; this was significantly inhibited by the high dose ethanol in human and rat PRP, but not whole blood. In contrast to our earlier studies with absolute ethanol, there was no evidence of hemolysis (and therefore, ADP release from red blood cells) using the current protocol. The results of these experiments show that alcohol, at physiologically relevant concentrations, has an inhibitory effect on secondary platelet aggregation responses to some agonists in whole blood as well as PRP, possibly by its previously demonstrated effects on arachidonic acid release by phospholipases. The possibility remains to be considered that other blood cells might contribute to the effects of alcohol on platelet aggregation in whole blood.

Re-evaluation of the effects of neuropeptide Y on aggregation of human platelets.

Several studies have shown that platelets are a major source of circulating neuropeptide Y (NPY) immunoreactivity in rats, but the effects of this vasoconstrictor peptide on platelets are not well-defined. Recently, it was reported that porcine NPY was an inhibitor of in vitro human platelet aggregation induced by epinephrine, an observation which would have important implications regarding platelet-vascular interactions during states involving platelet activation and thrombosis. Thus, we undertook the present studies, in an attempt to confirm the earlier report, and to extend those observations to human NPY. In contrast to the recent report, we found no inhibitory effect of either human or porcine NPY on epinephrine- or collagen-induced aggregation of human platelets from normal subjects. Likewise, specific NPY Y-1 and Y-2 agonists had no direct or indirect action on platelet aggregation. Finally, the effect of human NPY on intraplatelet cAMP was measured. The peptide had no effect on either basal or iloprost-stimulated cAMP levels. We hypothesize that the role of NPY in the platelet-vascular interaction is in promoting vasoconstriction associated with platelet aggregation, and does not include inhibition of further thrombosis.

Synthesis and structure-activity relationships of novel arylalkyl 4-benzyl piperazine derivatives as sigma site selective ligands.

Continuing our previous work that established that some chromones substituted by an aryl alkyl piperazino alkyl side chain are potent and selective sigma ligands and could be interesting in the treatment of psychosis, we synthesized 60 new compounds, replacing the chromone moiety by various cyclic systems. Many derivatives bind to the sigma sites in the nanomolar range and are generally selective in comparison with 5HT(1A) and the D(2) receptors. One of the most potent ligands of these series, 1-(2-naphthyl methyl)-4-benzyl piperazine 29, has been studied in various pharmacological tests. Although it doesn't have potential in the treatment of psychosis, the results we obtained confirm the data which indicates that such derivatives could be interesting in the treatment of inflammatory diseases.

Gingival recession in the mandibular central incisor region of Saudi schoolchildren aged 10-15 years.

Incidence of gingival recession in the mandibular central incisor region was examined in a sample of 1336 male and female Saudi schoolchildren aged from 10-15 yr. Gingival recession was found in 9.88% with no significant difference in the affected teeth by age (p greater than 0.8361). There was a significant difference in the mean clinical crown length between the affected and adjacent teeth (p less than 0.0001). The highest significant association of gingival recession was found with inflammation (p less than 0.0001), anterior crowding (p less than 0.0009) and frenal involvement (p less than 0.0001). The results of this investigation suggest that future studies should be made to evaluate the effect of miswak as a cleansing agent for the gingival tissues among the Saudi population.

Dental caries prevalence in intermediate Saudi schoolchildren in Riyad.

The study was performed in 1378 intermediate Saudi schoolchildren in Riyad, 693 females and 685 males. The results indicate low caries prevalence among Saudi children. This may be due to the type of food eaten, and other factors could be important, e.g. the use of miswak by Saudi children as the traditional practice for brushing teeth. The difference between the DMFT of the total number of Saudi females and males by sex and age were not statistically significant, P greater than 0.7498 and P greater than 0.1808, respectively. The chi-square analysis for treatment needs between females and males indicate that the differences were not statistically significant (chi 2 = 0.254, 1 df, P = 0.6145). The most prominent finding was a high percent (77.65%) of treatment needs for Saudi children. This confirmed the continuous need for planning and delivering dental services.

Periodontal disease prevalence and dental needs among schoolchildren in Saudi Arabia.

The study population consisted of 1174 intermediate Saudi schoolchildren; 601 girls and 573 boys, aged 13, 14 and 15 years. periodontal disease was assessed by the method recommended by WHO and data were computerized by using IBM 3033, SAS package. Boys had significantly higher debris, calculus deposits and intense gingivitis counts than girls by sex and age. But for advanced periodontal involvement, the result shows no significant differences by sex and age. There was a position correlation between debris, calculus and periodontal diseases. There was a highly significant difference between girls and boys. The results of this study suggest the need for an oral health program for the entire community.