Post-COVID syndrome: analysis of the prevalence of chemosensory dysfunction and predictive factors of recovery in COVID-19 long-haulers in Jordan.

OBJECTIVE: One of the major concerns of the post-COVID-19 era is elucidating and addressing the long-term complications of COVID-19. SUBJECTS AND METHODS: A web-based questionnaire was distributed in Jordan to assess the prevalence and recovery from chemosensory dysfunction among COVID-19 long-haulers in Jordan. RESULTS: A total of 611 respondents complained of chemosensory dysfunction (age range = 18-68 years), and the majority of the respondents were female (88.4%). Parosmia was the most prevalent olfactory dysfunction reported (n = 337, 33.3%), and parageusia was the most frequently reported gustatory dysfunction (n = 239, 36.4%). Medications were not reported to be associated with a better perception of smell or taste by nearly half of those who had been treated (n = 146, 46.1%). Among participants who had received olfactory rehabilitation/training (n = 215, 35.2%), 43.7% (n = 94) reported modest improvement, with the most frequently helpful scents being coffee (n = 80, 24.8%), aromatic oils (n = 74, 23%), and perfumes/colognes (n = 73, 22.7%). Age was found to have a significant negative correlation with complete recovery. In addition, age (p < .05), anosmia (p < .001), hyperosmia (p < .001), ageusia (p < .05), and duration of olfactory dysfunction (p < .001) were all independent predictors of complete recovery. CONCLUSIONS: Chemosensory dysfunctions are largely subjective; therefore, more objective examinations are required to draw more definite conclusions.

Reduced placental size and increased apoptosis are associated with prenatal nicotine exposure in rats.

OBJECTIVE: Smoking during pregnancy has been linked to a variety of negative embryonic and neonatal consequences. Nicotine is the major constituent of tobacco smoke, which was associated with adverse impacts on histological and functional features of the placenta. This study aims to investigate the potential influence of nicotine exposure on the rat placenta and fetus. MATERIALS AND METHODS: Nicotine was administrated through the drinking water of female pregnant rats. The placental size, as well as the fetal body weight and size, were measured at E20. The mRNA expression of the Bax gene (pro-apoptotic), the Bcl-2 gene (anti-apoptotic) and the angiogenic genes VEGF, Flt-1, and HIF1 were measured in placental tissue. Furthermore, Immunohistochemistry (IHC) using Bax, caspase 9 and VEGF antibodies were performed on placental sections. RESULTS: The results of the current study showed a significant reduction in the size of the placenta along with fetal body weight in nicotine treated group compared to the control group. Apoptosis was observed to be boosted in the placentas of the nicotine-treated group. This was associated with upregulation of Bax expression combined with no change in the expression of Bcl-2 in the treated group. On the other hand, there was no difference in the expression of angiogenic factors VEGF, Flt-1, or HIF1 between tested groups. CONCLUSIONS: In utero nicotine exposure in pregnant rats showed deleterious impacts on fetus growth and weight, as well as placental size. These were accompanied by increased apoptosis within the placenta, as revealed by Bax gene upregulation.

First Lebanese Antibiotic Awareness Week campaign: knowledge, attitudes and practices towards antibiotics.

Antibiotic resistance (ABR) is a major global health threat that increases the risk of treatment failure and increases medical costs. One of the most common factors contributing to the spread of ABR is self-medication. The public, as well as workers in clinical and veterinary sectors, commit false practices towards appropriate antibiotic use, favouring the spread of resistance. As such, the first Lebanese Antibiotic Awareness Week campaign was initiated with a human-centred and interactive approach. The data showed a strikingly low level of antibiotic awareness. Cooperation between relevant stakeholders, policy-makers and health actors is crucial to control and overcome the problem of ABR.

On the stability of a class of slowly varying systems.

Slowly varying systems are common in physics and control engineering and thus stability analysis for those systems has drawn considerable attention in the literature. This paper uses the "frozen time approach" to derive Lyapunov inequality conditions for the stability of a wide class of slowly varying systems. These conditions refine those developed in (Khalil in Nonlinear Systems, 2002) and display generality and effectiveness for both linear and nonlinear systems. To illustrate the utility of the proposed results, an example has been included.

Prévalence et facteurs de risque de la carie dentaire chez l'adolescent : étude réalisée dans les collèges de la préfecture CASA-ANFA

Introduction : Une étude épidémiologique descriptive de l'état bucco-dentaire des adolescents, a été menée dans le but de déterminer la prévalence, et les facteurs de risque de la maladie carieuse en milieu scolaire.Matériels et méthodes : L'enquête a concerné un échantillon de 1003 adolescents âgés de 12 à 18 ans scolarisés au sein de collèges publiques et privés de la région CASA-ANFA. Le niveau socio-économique, le niveau d'instruction de parents, la consommation de sucreries, les habitudes d'hygiène bucco-dentaire, la prévalence de la carie, l'indice CAOD (Nombre de dents permanentes cariées, absentes et obturées), et le MIH (Hypominéralisation molaire incisive) ont été étudiés.Résultats : La prévalence de la carie était élevée (74,9%), l'indice CAOD présentait une moyenne de 3,15 (écart type : 2,699), et le taux du MIH était de 16,0%. Les résultats obtenus ont confirmé une association statistiquement significative entre la carie dentaire et la fréquence de consommation de sucreries par les adolescents (p = 0,000043), entre le MIH et la carie dentaire (p = 0,034821), et aussi entre les habitudes de brossage dentaire et le niveau d'instruction des parents (p = 0,000378). Ces informations montrent la nécessité de développer un programme régional de promotion de la santé bucco-dentaire chez les adolescents en milieu scolaire

Mcl-1 is a key regulator of the ovarian reserve.

A majority of ovarian follicles are lost to natural death, but the disruption of factors involved in maintenance of the oocyte pool results in a further untimely follicular depletion known as premature ovarian failure. The anti-apoptotic B-cell lymphoma 2 (Bcl-2) family member myeloid cell leukemia-1 (MCL-1) has a pro-survival role in various cell types; however, its contribution to oocyte survival is unconfirmed. We present a phenotypic characterization of oocytes deficient in Mcl-1, and establish its role in maintenance of the primordial follicle (PMF) pool, growing oocyte survival and oocyte quality. Mcl-1 depletion resulted in the premature exhaustion of the ovarian reserve, characterized by early PMF loss because of activation of apoptosis. The increasingly diminished surviving cohort of growing oocytes displayed elevated markers of autophagy and mitochondrial dysfunction. Mcl-1-deficient ovulated oocytes demonstrated an increased susceptibility to cellular fragmentation with activation of the apoptotic cascade. Concomitant deletion of the pro-apoptotic Bcl-2 member Bcl-2-associated X protein (Bax) rescued the PMF phenotype and ovulated oocyte death, but did not prevent the mitochondrial dysfunction associated with Mcl-1 deficiency and could not rescue long-term breeding performance. We thus recognize MCL-1 as the essential survival factor required for conservation of the postnatal PMF pool, growing follicle survival and effective oocyte mitochondrial function.

Modified neocortical and cerebellar protein expression and morphology in adult rats following prenatal inhibition of the kynurenine pathway.

Inhibition of the kynurenine pathway of tryptophan metabolism during gestation can lead to changes in synaptic transmission, neuronal morphology and plasticity in the rat hippocampus. This suggests a role for the kynurenine pathway in early brain development, probably caused by kynurenine modulation of N-methyl-d-aspartate (NMDA) glutamate receptors which are activated by the tryptophan metabolite quinolinic acid and blocked by kynurenic acid. We have now examined samples of neocortex and cerebellum of adult animals to assess the effects of a prenatally administered kynurenine-3-monoxygenase inhibitor (Ro61-8048) on protein and mRNA expression, dendritic structure and immuno-histochemistry. No changes were seen in mRNA expression using quantitative real-time polymerase chain reaction. Changes were detected in the expression of several proteins including the GluN2A subunit, unco-ordinated-5H3 (unc5H3), doublecortin, cyclo-oxygenase, sonic hedgehog and Disrupted in schizophrenia-1 (DISC1), although no differences in immunoreactive cell numbers were observed. In the midbrain, dependence receptor expression was also changed. The numbers and lengths of individual dendritic regions were not changed but there were significant increases in the overall complexity values of apical and basal dendritic trees. The data support the hypothesis that constitutive kynurenine metabolism plays a critical role in early, embryonic brain development, although fewer effects are produced in the neocortex and cerebellum than in the hippocampus and the nature of the changes seen are qualitatively different. The significant changes in DISC1 and unc5H3 may be relevant to cerebellar dysfunction and schizophrenia respectively, in which these proteins have been previously implicated.

Prenatal inhibition of the kynurenine pathway leads to structural changes in the hippocampus of adult rat offspring.

Glutamate receptors for N-methyl-d-aspartate (NMDA) are involved in early brain development. The kynurenine pathway of tryptophan metabolism includes the NMDA receptor agonist quinolinic acid and the antagonist kynurenic acid. We now report that prenatal inhibition of the pathway in rats with 3,4-dimethoxy-N-[4-(3-nitrophenyl)thiazol-2-yl]benzenesulphonamide (Ro61-8048) produces marked changes in hippocampal neuron morphology, spine density and the immunocytochemical localisation of developmental proteins in the offspring at postnatal day 60. Golgi-Cox silver staining revealed decreased overall numbers and lengths of CA1 basal dendrites and secondary basal dendrites, together with fewer basal dendritic spines and less overall dendritic complexity in the basal arbour. Fewer dendrites and less complexity were also noted in the dentate gyrus granule cells. More neurons containing the nuclear marker NeuN and the developmental protein sonic hedgehog were detected in the CA1 region and dentate gyrus. Staining for doublecortin revealed fewer newly generated granule cells bearing extended dendritic processes. The number of neuron terminals staining for vesicular glutamate transporter (VGLUT)-1 and VGLUT-2 was increased by Ro61-8048, with no change in expression of vesicular GABA transporter or its co-localisation with vesicle-associated membrane protein-1. These data support the view that constitutive kynurenine metabolism normally plays a role in early embryonic brain development, and that interfering with it has profound consequences for neuronal structure and morphology, lasting into adulthood.

Prenatal activation of maternal TLR3 receptors by viral-mimetic poly(I:C) modifies GluN2B expression in embryos and sonic hedgehog in offspring in the absence of kynurenine pathway activation.

Activation of the immune system during pregnancy is believed to lead to psychiatric and neurological disorders in the offspring, but the molecular changes responsible are unknown. Polyinosinic:polycytidylic acid (poly(I:C)) is a viral-mimetic double-stranded RNA complex which activates Toll-Like-Receptor-3 and can activate the metabolism of tryptophan through the oxidative kynurenine pathway to compounds that modulate activity of glutamate receptors. The aim was to determine whether prenatal administration of poly(I:C) affects the expression of neurodevelopmental proteins in the offspring and whether such effects were mediated via the kynurenine pathway. Pregnant rats were treated with poly(I:C) during late gestation and the offspring were allowed to develop to postnatal day 21 (P21). Immunoblotting of the brains at P21 showed decreased expression of sonic hedgehog, a key protein in dopaminergic neuronal maturation. Expression of α-synuclein was decreased, while tyrosine hydroxylase was increased. Disrupted in Schizophrenia-1 (DISC-1) and 5-HT2C receptor levels were unaffected, as were the dependence receptors Unc5H1, Unc5H3 and Deleted in Colorectal Cancer (DCC), the inflammation-related transcription factor NFkB and the inducible oxidative enzyme cyclo-oxygenase-2 (COX-2). An examination of embryo brains 5 h after maternal poly(I:C) showed increased expression of GluN2B, with reduced doublecortin and DCC but no change in NFkB. Despite altered protein expression, there were no changes in the kynurenine pathway. The results show that maternal exposure to poly(I:C) alters the expression of proteins in the embryos and offspring which may affect the development of dopaminergic function. The oxidation of tryptophan along the kynurenine pathway is not involved in these effects.

[Striatopallidodentate calcinosis, hypoparathyroidism and neurological features: a case series study]. / Calcinose striatopallidodentelée, hypoparathyroïdie et atteinte neurologique: étude de série.

INTRODUCTION: The respective roles of hypocalcemia and intracerebral calcifications in the occurrence of various neurological manifestations in hypoparathyroidism is not entirely clear. Nevertheless, therapeutic and prognostic implications are important. OBJECTIVES: We analyze the neurological clinical aspects observed in hypoparathyroidism and correlate them to the biological calcium abnormality and radiological CT scan findings. We also compare these results with data reported in the idiopathic form of striatopallidodentate calcinosis. PATIENTS: The neurological clinical, CT scan findings and outcome have been retrospectively studied in patients recruited during 13 years (2000-2012) for neurological features associated with hypoparathyroidism or pseudohypoparathyroidism. RESULTS: Twelve patients with primary hypoparathyroidism (n=5), secondary to thyroidectomy (n=4) and pseudohypoparathyroidism (n=3) were studied. The sex-ratio was 1 and mean age was 39 years. All patients had a tetany, 60% had epilepsy, associated in one patient with "benign" intracranial hypertension; 50% had behavioral changes. Response to calcium therapy was excellent for all these events. Moderate cognitive deficit was noted in three patients (25%), parkinsonism in two patients and hyperkinetic movement disorders in one other. These events were not responsive to calcium therapy and were more common in cases of extensive brain calcifications and in patients who had pseudohypoparathroidism. COMMENTS: This study suggests that, in patients with hypoparathyroidism, epilepsy and psychiatric disorders are induced by hypocalcemia and reversible after its correction. Cognitive and extrapyramidal impairment seem to be related to the progressive extension of intracerebral calcification, particularly in patients with a late diagnosis. In patients with pseudohypoparathyroidism, this finding is different because of the contribution of other factors, specific to this disease.

Prenatal inhibition of the tryptophan-kynurenine pathway alters synaptic plasticity and protein expression in the rat hippocampus.

Glutamate receptors sensitive to N-methyl-d-aspartate (NMDA) are important in early brain development, influencing cell proliferation and migration, neuritogenesis, axon guidance and synapse formation. The kynurenine pathway of tryptophan metabolism includes an agonist (quinolinic acid) and an antagonist (kynurenic acid) at these receptors. Rats were treated in late gestation with 3,4-dimethoxy-N-[4-(3-nitrophenyl)thiazol-2-yl]-benzene-sulphonamide (Ro61-8048), an inhibitor of kynurenine-3-monoxygenase which diverts kynurenine metabolism to kynurenic acid. Within 5h of drug administration, there was a significant decrease in GluN2A expression and increased GluN2B in the embryo brains, with changes in sonic hedgehog at 24h. When injected dams were allowed to litter normally, the brains of offspring were removed at postnatal day 21 (P21). Recordings of hippocampal field excitatory synaptic potentials (fEPSPs) showed that prenatal exposure to Ro61-8048 increased neuronal excitability and paired-pulse facilitation. Long-term potentiation was also increased, with no change in long-term depression. At this time, levels of GluN2A, GluN2B and postsynaptic density protein PSD-95 were all increased. Among several neurodevelopmental proteins, the expression of sonic hedgehog was increased, but DISC1 and dependence receptors were unaffected, while raised levels of doublecortin and Proliferating Cell Nuclear Antigen (PCNA) suggested increased neurogenesis. The results reveal that inhibiting the kynurenine pathway in utero leads to molecular and functional synaptic changes in the embryos and offspring, indicating that the pathway is active during gestation and plays a significant role in the normal early development of the embryonic and neonatal nervous system.

Prenatal activation of Toll-like receptors-3 by administration of the viral mimetic poly(I:C) changes synaptic proteins, N-methyl-D-aspartate receptors and neurogenesis markers in offspring.

BACKGROUND: There is mounting evidence for a neurodevelopmental basis for disorders such as autism and schizophrenia, in which prenatal or early postnatal events may influence brain development and predispose the young to develop these and related disorders. We have now investigated the effect of a prenatal immune challenge on brain development in the offspring. Pregnant rats were treated with the double-stranded RNA polyinosinic:polycytidylic acid (poly(I:C); 10 mg/kg) which mimics immune activation occurring after activation of Toll-like receptors-3 (TLR3) by viral infection. Injections were made in late gestation (embryonic days E14, E16 and E18), after which parturition proceeded naturally and the young were allowed to develop up to the time of weaning at postnatal day 21 (P21). The brains of these animals were then removed to assess the expression of 13 different neurodevelopmental molecules by immunoblotting. RESULTS: Measurement of cytokine levels in the maternal blood 5 hours after an injection of poly(I:C) showed significantly increased levels of monocyte chemoattractant protein-1 (MCP-1), confirming immune activation. In the P21 offspring, significant changes were detected in the expression of GluN1 subunits of NMDA receptors, with no difference in GluN2A or GluN2B subunits or the postsynaptic density protein PSD-95 and no change in the levels of the related small GTPases RhoA or RhoB, or the NMDA receptor modulator EphA4. Among presynaptic molecules, a significant increase in Vesicle Associated Membrane Protein-1 (VAMP-1; synaptobrevin) was seen, with no change in synaptophysin or synaptotagmin. Proliferating Cell Nuclear Antigen (PCNA), as well as the neurogenesis marker doublecortin were unchanged, although Sox-2 levels were increased, suggesting possible changes in the rate of new cell differentiation. CONCLUSIONS: The results reveal the induction by prenatal poly(I:C) of selective molecular changes in the brains of P21 offspring, affecting primarily molecules associated with neuronal development and synaptic transmission. These changes may contribute to the behavioural abnormalities that have been reported in adult animals after exposure to poly(I:C) and which resemble symptoms seen in schizophrenia and related disorders.

Cat's whiskers tea (Orthosiphon stamineus) extract inhibits growth of colon tumor in nude mice and angiogenesis in endothelial cells via suppressing VEGFR phosphorylation.

Cat's whiskers (Orthosiphon stamineus) is commonly used as Java tea to treat kidney stones including a variety of angiogenesis-dependent diseases such as tumorous edema, rheumatism, diabetic blindness, and obesity. In the present study, antitumor potential of standardized 50% ethanol extract of O. stamineus leaves (EOS) was evaluated against colorectal tumor in athymic mice and antiangiogenic efficacy of EOS was investigated in human umbilical vein endothelial cells (HUVEC). EOS at 100 mg/kg caused 47.62 ± 6.4% suppression in tumor growth, while at 200 mg/kg it caused 83.39 ± 4.1% tumor regression. Tumor histology revealed significant reduction in extent of vascularization. Enzyme-linked immunosorbent assay showed EOS (200 mg/kg) significantly reduced the vascular endothelial growth factor (VEGF) level in vitro (211 ± 0.26 pg/ml cell lysate) as well as in vivo (90.9 ± 2 pg/g tissue homogenate) when compared to the control (378 ± 5 and 135.5 ± 4 pg, respectively). However, EOS was found to be noncytotoxic to colon cancer and endothelial cells. In vitro, EOS significantly inhibited the migration and tube formation of human umbilical vein endothelial cells (HUVECs). EOS suppressed VEGF-induced phosphorylation of VEGF receptor-2 in HUVECs. High performance liquid chromatography (HPLC) analysis of EOS showed high rosmarinic acid contents, whereas phytochemical analysis revealed high protein and phenolic contents. These results demonstrated that the antitumor activity of EOS may be due to its VEGF-targeted antiangiogenicity.

Photophysical properties and localization of chlorins substituted with methoxy groups, hydroxyl groups and alkyl chains in liposome-like cellular membrane.

Some of the photophysical properties (stationary absorbance and fluorescence, fluorescence decay times and singlet oxygen quantum yields) of chlorins substituted with methoxy groups, hydroxyl groups and hydrocarbonic chains were studied in ethanol and dipalmitoyl-phosphatidylcholine (DPPC) liposomes using steady-state and time-resolved fluorescence spectroscopies. The photophysical behaviors of the chlorins in liposomes like cellular membrane were compared with those obtained from chlorin-liposome systems delivered to Jurkat cells in order to select potent photosensitizers for the photodynamic treatment of cancer. The localization of the studied chlorins inside liposomes was found to depend strongly on the substituents of chlorins. Absorption spectra of chlorins embedded in DPPC-liposomes have been recorded in the temperature range of 20-70 degrees C. It is demonstrated that the location of the chlorin molecules depends on the phase state of the phospholipids. These observations are confirmed by the fluorescence lifetimes, singlet oxygen lifetimes and singlet oxygen quantum yields results.

A new approach in the management of lower Mullerian atresia.

Over the past 20 years we have encountered 13 cases of lower genital tract atresia or obstruction. There were eight cases due to a high transverse vaginal septum. These were dealt with by standard surgical reconstruction. One later recurred and required hysterectomy. Five patients presented with cervical atresia. These were successfully treated by a new abdomino/vaginal approach. All menstruated normally after the procedure and one became pregnant and delivered a normal baby by caesarean section at term. None of the cases had recurrent obstruction and none required hysterectomy.

Poly(dA).poly(dT) rich sequences are not sufficient to exclude nucleosome formation in a constitutive yeast promoter.

It was suggested that poly(dA).poly(dT) rich sequences in yeast Saccharomyces cerevisiae act as elements of constitutive promoters by exclusion of nucleosomes (Struhl, K. (1985). Proc. Natl. Acad. Sci. USA 82, 8419-8423). We have mapped the chromatin structure of the pet56-his3-ded1 region in minichromosomes and show that the poly(dA).poly(dT) sequences are located in nuclease sensitive regions. DNA fragments from the nuclease sensitive promoter region of DED1 were used for nucleosome reconstitution in vitro. We show that all sequences can form nucleosome cores and that the poly(dA).poly(dT) sequence can be incorporated in nucleosome cores. The results suggest that the nuclease sensitivity found in vivo is not established by poly(dA).poly(dT) mediated exclusion of nucleosomes.