Corona Virus Disease-19 serology, inflammatory markers, hospitalizations, case finding, and aging.

Most deaths from severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection occur in older subjects. We assessed the utility of serum inflammatory markers interleukin-6 (IL-6), C reactive protein (CRP), and ferritin (Roche, Indianapolis, IN), and SARS-CoV-2 immunoglobulin G (IgG), immunoglobulin M (IgM), and neutralizing antibodies (Diazyme, Poway, CA). In controls, non-hospitalized subjects, and hospitalized subjects assessed for SARS-CoV-2 RNA (n = 278), median IgG levels in arbitrary units (AU)/mL were 0.05 in negative subjects, 14.83 in positive outpatients, and 30.61 in positive hospitalized patients (P<0.0001). Neutralizing antibody levels correlated significantly with IgG (r = 0.875; P<0.0001). Having combined values of IL-6 ≥10 pg/mL and CRP ≥10 mg/L occurred in 97.7% of inpatients versus 1.8% of outpatients (odds ratio 3,861, C statistic 0.976, P = 1.00 x 10-12). Antibody or ferritin levels did not add significantly to predicting hospitalization. Antibody testing in family members and contacts of SARS-CoV-2 RNA positive cases (n = 759) was invaluable for case finding. Persistent IgM levels were associated with chronic COVID-19 symptoms. In 81,624 screened subjects, IgG levels were positive (≥1.0 AU/mL) in 5.21%, while IgM levels were positive in 2.96% of subjects. In positive subjects median IgG levels in AU/mL were 3.14 if <30 years of age, 4.38 if 30-44 years of age, 7.89 if 45-54 years of age, 9.52 if 55-64 years of age, and 10.64 if ≥65 years of age (P = 2.96 x 10-38). Our data indicate that: 1) combined IL-6 ≥10 pg/mL and CRP ≥10 mg/L identify SARS-CoV-2 positive subjects requiring hospitalization; 2) IgG levels were significantly correlated with neutralizing antibody levels with a wide range of responses; 3) IgG levels have significant utility for case finding in exposed subjects; 4) persistently elevated IgM levels are associated with chronic symptoms; and 5) IgG levels are significantly higher in positive older subjects than their younger counterparts.

Neutral and Multicharged Ions of Small Aluminum Oxides: Structures, Spectroscopy, and Energetics.

We use accurate ab initio methodologies at the Coupled Cluster level to compute the stable forms of AlxOyq+ (x = 1, 2; y = 1, 2; q = 0-3) species for which we derive an accurate set of geometrical and vibrational spectroscopic data. We also determine their adiabatic single, double, and triple ionization energies. These spectroscopic and thermodynamical data may help for identifying these species in laboratory, in astrophysical media, and in plasma and confirm previous observations of multi-charged AlxOy clusters by Atom Probe Tomography (ATP) coupled to mass spectrometry. They should help for identifying and understanding the complex chemical processes occurring during the Al2O3 growth in laboratory and in astrophysical media and those taking place at the degradation of Al-containing materials by high temperature corrosion/oxidation.

Preliminary national report on cystic fibrosis epidemiology in Tunisia: the actual state of affairs.

AIM: To establish a preliminary national report on clinical and genetic features of cystic fibrosis (CF) in Tunisian children as a first measure for a better health care organization. METHODS: All children with CF diagnosed by positive sweat tests between 1996 and 2015 in children's departments of Tunisian university hospitals were included. Data was recorded at diagnosis and during the follow-up from patients' medical records. RESULTS: In 12 departments, 123 CF children were collected. The median age at diagnosis was 5 months with a median diagnosis delay of 3 months. CF was revealed mostly by recurrent respiratory tract infections (69.9%), denutrition (55.2%), and/or chronic diarrhea (41.4%). The mean sweat chloride concentration was 110.9mmol/L. At least one mutation was found in 95 cases (77.2%). The most frequent mutations were Phe508del (n=58) and E1104X (n=15). Fifty-five patients had a Pseudomonas Aeruginosa chronic colonization at a median age of 30 months. Cirrhosis and diabetes appeared at a mean age of 5.5 and 12.5 years respectively in 4 patients each. Sixty-two patients died at a median age of 8 months. Phe508del mutation and hypotrophy were associated with death (p=0.002 and p<0.001, respectively). CONCLUSION: CF is life-shortening in Tunisia. Setting-up appropriate management is urgent.

Complexes of Zn(II)-Triazoles with CO2 and H2O: Structures, Energetics, and Applications.

Using a first-principle methodology, we investigate the stable structures of the nonreactive and reactive clusters formed between Zn2+-triazoles ([Zn2+-Tz]) clusters and CO2 and/or H2O. In sum, we characterized two modes of bonding of [Zn2+-Tz] with CO2/H2O: the interaction is established through (i) a covalent bond between Zn2+ of [Zn2+-Tz] and oxygen atoms of CO2 or H2O and (ii) hydrogen bonds through N-H or C-H of [Zn2+-Tz] and oxygen atoms of H2O or CO2, N-H···O. We also identified intramolecular proton transfer processes induced by complexation. Indeed, water drastically changes the shape of the energy profiles of the tautomeric phenomena through strong lowering of the potential barriers to tautomerism. The comparison to [Zn2+-Im] subunits formed with Zn2+ and imidazole shows that the efficiency of Tz-based compounds for CO2 capture and uptake is due to the incorporation of more accessible nitrogen donor sites in Tzs compared to imidazoles. Since [Zn2+-Tz] clusters are subunits of an organometallic nanoporous materials and Zn-proteins, our data are useful for deriving force fields for macromolecular simulations of these materials. Our work also suggests the consideration of traces of water to better model the CO2 sequestration and reactivity on macromolecular entities such as pores or active sites.

Report of the Tunisian Registry of Primary Immunodeficiencies: 25-Years of Experience (1988-2012).

PURPOSE: Primary immunodeficiencies (PIDs) are a large group of diseases characterized by susceptibility to not only recurrent infections but also autoimmune diseases and malignancies. The aim of this study was to describe and analyze the distribution, clinical features and eventual outcome of PID among Tunisian patients. METHODS: We reviewed the record of 710 patients diagnosed with Primary Immunodeficiency Diseases (PIDs) from the registry of the Tunisian Referral Centre for PIDs over a 25-year period. RESULTS: The male-to-female ratio was 1.4. The median age at the onset of symptoms was 6 months and at the time of diagnosis 2 years. The estimated prevalence was 4.3 per 100,000 populations. The consanguinity rate was found in 58.2 % of families. According to the International Union of Immunological Societies classification, spectrums of PIDs were as follows: combined T-cell and B-cell immunodeficiency disorders account for the most common category (28.6 %), followed by congenital defects of phagocyte (25.4 %), other well-defined immunodeficiency syndromes (22.7 %), predominant antibody deficiency diseases (17.7 %), diseases of immune dysregulation (4.8 %), defect of innate immunity (0.4 %) and complement deficiencies (0.4 %). Recurrent infections, particularly lower airway infections (62.3 %), presented the most common manifestation of PID patients. The overall mortality rate was 34.5 %, mainly observed with combined immunodeficiencies. CONCLUSION: The distribution of PIDs was different from that reported in Western countries, with a particularly high proportion of Combined Immunodeficiencies and phagocyte defects in number and/or function. More is needed to improve PID diagnosis and treatment in our country.

δ0-Thalassemia in cis of ßKnossos globin gene: first homozygous description in thalassemia intermedia Libyans and first combination with codon 39 (C→T) in thalassemia intermedia Tunisian patients.

BACKGROUND: ß-Thalassemia is the most common disease among hemoglobinopathies in North African and Arab populations. In the present study we report the first description of the ß-Knossos codon27 (G→T) (ßKnossos) allele in cis with the δ059 (-A) mutation in thalassemia intermedia patients in Tunisia and Libya. METHODS: This identification was carried out by sequencing analysis of the whole coding regions of the δ- and ß-globin genes. RESULTS: We noted that heterozygous inheritance of the ßKnossos mutation results in a mild ß-thalassemia phenotype with a low level of HbA2 while homozygous leads to intermediate ß-thalassemia with an atypical high performance liquid chromatogram showing a complete absence of HbA2 and HbF. Compound heterozygosity of the ßKnossos with ß0 codon39 (C→T) is identified in a Tunisian proband for the first time and gives rise to a mild phenotype. In both families, the δ0 codon59 (-A) and the ßKnossos alleles were found to be associated with a single Mediterranean ß-haplotype I similar to that observed in previous reports from Algeria, Egypt, Cyprus, and Turkey. CONCLUSIONS: The chromosome supporting the ßKnossos and the δ0 codon59 (-A) alleles seems to be of a single Mediterranean origin. Premarital screening studies in families in which only one of the parents has typical aspects of ß-thalassemia trait and the other has a normal HbA2 level associated with abnormal red cell indices becomes a necessity to avoid missing thalassemia carriers.

Transition m.3308T>C in the ND1 gene is associated with left ventricular hypertrabeculation/noncompaction.

Though left ventricular hypertrabeculation/noncompaction (LVNC) is frequently associated with mitochondrial DNA (mtDNA) mutations, it has not been reported in association with the transition m.3308T>C of the NADH dehydrogenase subunit 1 (ND1) gene. The index patient is a 16-year-old Tunisian female who was investigated for a systolic murmur and cardiomegaly. Echocardiography revealed tricuspid insufficiency, moderate left ventricular dilatation, Ebstein's anomaly, a superior caval vein draining into the coronary sinus and, surprisingly, LVNC of the apex and the lateral wall. LVNC was absent in all other cardiologically investigated siblings. RNA and mtDNA sequence analysis revealed the known homoplasmic mutation m.3308T>C resulting in the replacement of the first amino acid methionine by threonine in the ND1 subunit of respiratory chain complex I. The m.3308T>C mutation was also present in the patient's mother and several other family members but absent in 350 controls. Additionally, the index patient carried the polymorphisms m.8248A>G in the COX2 gene and m.8468C>T in the ATP8 gene. It is concluded that LVNC may be associated with the known homoplasmic m.3308T>C mutation in the ND1 gene. However, the pathogenetic role of this mutation in the development of LVNC remains elusive.

Self-protection as a driver for hand hygiene among healthcare workers.

A total of 2,725 healthcare workers in 8 Mediterranean countries replied to a self-assessment questionnaire that assessed their perceptions on hand hygiene. Responses revealed that rates of hand hygiene compliance before patient contact were significantly less than rates after patient contact (P < .001) and that use of soap and water was preferred over use of alcohol-based hand rub. These findings suggest that self-protection could be a major subliminal driver for performance of hand hygiene.

Screening of the DFNB3 locus: identification of three novel mutations of MYO15A associated with hearing loss and further suggestion for two distinctive genes on this locus.

Recessive mutations of MYO15A are associated with nonsyndromic hearing loss (HL) in humans (DFNB3) and in the shaker-2 mouse. Human MYO15A has 66 exons and encodes unconventional myosin XVA. Analysis of 77 Tunisian consanguineous families segregating recessive deafness revealed evidence of linkage to microsatellite markers for DFNB3 in four families. In two families, sequencing of MYO15A led to the identification of two novel homozygous mutations: a nonsense (c.4998C>A (p.C1666X) in exon 17 and a splice site mutation in intron 54 (c.9229 + 1G>A). A novel mutation of unknown significance, c.7395 + 3G>C, was identified in the third family, and no mutation was found in the fourth family. In conclusion, we discovered three novel mutations of MYO15A, and our data suggest the possibility that there are two distinct genes at the DFNB3 locus.

Self-medication with antibiotics in the ambulatory care setting within the Euro-Mediterranean region; results from the ARMed project.

Anecdotal data from the southern and eastern Mediterranean region suggests that self-medication with antibiotics is commonly practiced in many countries. In order to provide proper information on the situation, we undertook short structured interviews in out-patients clinics or primary health centres in Cyprus, Egypt, Jordan, Lebanon, Libya, Tunisia and Turkey. A total of 2109 interviews were undertaken of which 1705 completed the full questionnaire. Self-medication was reported by 19.1% (<0.1% in Cyprus to 37% in Lebanon) of respondents. Intended self-medication ranged from 1.3% (95% CI 0%, 3%) in Cyprus to 70.7% (95% CI 64%, 77%) in Jordan. Upper respiratory tract symptoms were the most frequent reasons for which respondents indicated they would self-medicate. 48.4% of the whole group replied that they kept antibiotics at home, being highest in Lebanon (60%, 95% CI 51%, 69%). We found a significant association between antibiotic hoarders and intended users of antibiotics for self-medication. Our data confirms that non-prescribed antibiotic use is high within ambulatory care in southern and eastern Mediterranean countries, being almost twice that reported in a similar European study. Corrective efforts are clearly required in the region to ensure proper use of antimicrobials so as to reduce pressure for antimicrobial resistance.

Association between antibiotic use and changes in susceptibility patterns of Pseudomonas aeruginosa in an intensive care burn unit: a 5-year study, 2000-2004.

This study aimed to evaluate the relationship between antimicrobial resistance in Pseudomonas aeruginosa and annual antibiotic use in a burn unit. From 1 January 2000 to 31 December 2004, 203 non-repetitive strains of Ps. aeruginosa were recovered from various clinical specimens. Antimicrobial susceptibility testing was performed using the disc diffusion method, and susceptibility data were interpreted according to break points recommended by the French Society of Microbiology. The antibiotic consumption for imipenem, ceftazidime, cefotaxime, piperacillin-tazobactam, ofloxacin, ciprofloxacin, gentamicin and amikacin was calculated with antimicrobial density. The relationship between antibiotic use and the resistance of Ps. aeruginosa was analysed. The consumption of ceftazidime and amikacin showed no association with resistance. A statistically significant relationship was observed between increasing use of ciprofloxacin and the incidence of resistant Ps. aeruginosa to this antibiotic (rs=0.89, p=0.05), and a significant correlation between ciprofloxacin consumption and resistance to imipenem was noted (rs=0.89, p=0.043). Restricted use of ciprofloxacin during 2003 and 2004 was followed by a significant decrease of resistance in Ps. aeruginosa. Our report illustrates the major role of ciprofloxacin in the emergence of resistant Ps. aeruginosa.

A novel mitochondrial DNA tRNAIle (m.4322dupC) mutation associated with idiopathic dilated cardiomyopathy.

We identified a novel heteroplasmic mitochondrial DNA (mtDNA) (m.4322dupC) mutation in tRNA gene associated with isolated dilated cardiomyopathy (DCM) as maternal trait. Mutation screening techniques and automated DNA sequencing were performed to identify mtDNA mutations and to assess heteroplasmy in family's proband and healthy control subjects. All family members tested had heteroplasmic mtDNA m.4322dupC mutation. We also screened 350 normal controls for this mutation and found no evidence of heteroplasmy. The m.4322dupC mutation was found in the skeletal tissue from the proband that exhibited slightly reduced deficiency of mitochondrial respiratory chain enzymes (complex III). The present study reports the novel m.4322dupC mutation in tRNA gene, which is possibly associated to the disease, to isolated DCM. It was localized in a hot-spot region for mutations and is possibly pathogenic because of a cosegregation with the matrilineal transmission of DCM.

[Epidemiological profile and antibiotic susceptibility of Pseudomonas aeruginosa isolates within the burned patient hospitalized in the intensive care burn unit]. / Profil epidemiologique et sensibilite aux antibiotiques des souches de Pseudomonas aeruginosa isolees dans un service de reanimation des brules.

BACKGROUND: Pseudomonas aeruginosa plays a predominant role as an etiological agent involved in serious infections in burned patients. Treatment of these infections is frequently complicated by antibiotic resistance, a problem that is is increasing in recent years. AIM: The objective of this study is to analyze epidemiological profile and antibiotic susceptibility of P. aeruginosa isolates within the burned patients admitted in our intensive care department. METHODS: During a period of 4 years (2000/2003), 828 burn patients were admitted. RESULTS: The survey of antibiotic susceptibility of P. aeruginosa showed high percentages of resistance to the different antibiotics. 60.9% of strains were resistant to piperacillin, 53.4% to ceftazidime, 37.6% to imipenem, 70.6% to cefsulodine, 59.3% to tobramycin, 80% to gentamicin, 62.4% to amikacin and 53.4% to ciprofloxacin. CONCLUSION: It is necessary to implement urgent measures to prevent the spreading of this multiresistant strain. These measures include: sensible limitation of the use of antimicrobial agent, strict disinfection and hygienic procedures.

Clinical and genetic analysis of two Tunisian otosclerosis families.

Otosclerosis is caused by an abnormal bone homeostasis of the otic capsule resulting in a conductive hearing loss when the free motion of the stapes is compromised. An additional sensorineural hearing loss arises in some patients, most likely due to otosclerotic foci that invade the cochlear endosteum. Otosclerosis is a very common hearing impairment among Caucasians with a prevalence of about 0.3-0.4% among white adults. In the majority of cases, otosclerosis can be considered as a complex disease, caused by both genetic as environmental factors, but autosomal dominant forms of otosclerosis exist. However, families large enough for genetic analysis are very rare and often show reduced penetrance. To date five loci have been reported, but none of the genes have been cloned yet. In this study, we analyzed two new autosomal dominant otosclerosis families from Tunisia, and genotyped them with microsatellite markers for the known loci, the collagen genes COL1A1 and COL1A2, and NOG gene. In the family LK, linkage to all known loci was excluded. However, the family LS shows suggestive linkage to the OTSC3 region on chromosome 6p21.3-p22.3. This result points out that, besides the five reported loci, there must be at least one additional locus for autosomal dominant otosclerosis.

[Bacteriological profile of bacteremias in badly burnt patients]. / Profil bacteriologique des bacteriemies chez les brules.

The purpose of this work is to study the bacteriological profiles of germ responsible for bacteriemas / septicemias in badly burnt patients hospitalized in burns utis, in order to guide better the antibiotherapy of first intention. During the period of survey going from January 1st, 2001 to December 31st,2002 71 patients had one or several episodes of bateremia. The average burnt cutaneous surface was 48.7%. All collected bacteriemas were contacted in hospial. Empirical antbiotheray was effective in 30 patients. The hospital stay for this group was long: 45 to 86 days. Acinetobacter baumannii was the most incriminated germ(20.3%), followed klebsiella pneumoniea (12.7%). The frequency of resistance was variable according to the considered species.

[Chronic septic granulomatosis in children revealed by invasive pulmonary aspergillosis]. / La granulomatose septique chronique chez l'enfant revelee par une aspergillose pulmonaire invasive.

Chronic granulomatosis disease (GCD) is a hereditary abnormality of phagocytic cells, frequently revealed by invasive pulmonary Aspergillosis. The authors report the case of 8 year old girl investigates for hypotrophia, reccurent lung disease and hemoptysia. She was treated for pulmonary tuberculosis because of biological inflammatory syndrome, right alveolar opacity and positive tuberculin skin test. The course was marked by the developement of a thoracic wall mass. Anti- aspergillus serology was positive; culture of the thoracic mass puncture and bronchoalveolar lavage isolated fumigatus Aspergillus. GCD was suggested and confirmed by the NBT test.

Are there regional variations in the diagnosis, surveillance, and control of methicillin-resistant Staphylococcus aureus?

OBJECTIVE: To assess the way healthcare facilities (HCFs) diagnose, survey, and control methicillin-resistant Staphylococcus aureus (MRSA). DESIGN: Questionnaire. SETTING: Ninety HCFs in 30 countries. RESULTS: Evaluation of susceptibility testing methods showed that 8 laboratories (9%) used oxacillin disks with antimicrobial content different from the one recommended, 12 (13%) did not determine MRSA susceptibility to vancomycin, and 4 (4.5%) reported instances of isolation of vancomycin-resistant S. aureus but neither confirmed this resistance nor alerted public health authorities. A MRSA control program was reported by 55 (61.1%) of the HCFs. The following isolation precautions were routinely used: hospitalization in a private room (34.4%), wearing of gloves (62.2%), wearing of gowns (44.4%), hand washing by healthcare workers (53.3%), use of an isolation sign on the patient's door (43%), or all four. When the characteristics of HCFs with low incidence rates (< 0.4 per 1,000 patient-days) were compared with those of HCFs with high incidence rates (> or = 0.4 per 1,000 patient-days), having a higher mean number of beds per infection control nurse was the only factor significantly associated with HCFs with high incidence rates (834 vs 318 beds; P = .02). CONCLUSION: Our results emphasize the urgent need to strengthen the microbiologic and epidemiologic capacities of HCFs worldwide to prevent MRSA transmission and to prepare them to address the possible emergence of vancomycin-resistant S. aureus.