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Abstract Fluoroquinolone-resistant (FQs-R) microorganisms causing infectious complications after ultrasound-guided needle biopsy of the prostate (TRUS-BP) have become an important challenge in healthcare settings globally, questioning the continued utility of FQ as the preferred prophylactic agent. This study aimed to characterize molecular mechanisms of resistance on FQs-R E. coli isolated from the enteric microbiota of patients undergoing (TRUS-BP) and to highlight their impact on Minimum Inhibitory Concentrations (MICs). From February 2016 to December 2018, the incidence of rectal carriage of Qs-FQs resistant Enterobacterales detected from rectal swabs of patients before undergoing (TRUS-BP) was 61.06% (80/131) all related to E. coli species. Based on the MICs range of Qs (24–256 mg/L) and FQs (0.24–128 mg/L) breakpoint by EUCAST, we categorized these E. coli isolates into three resistance profiles (I, II, and III) associated with the patterns of chromosomal mutations in the quinolone resistance-determining regions (QRDRs) of gyrA and parC and the plasmid-mediated quinolone resistance encoding genes (PMQRs) detected by PCR-based assay and sequencing; MICs increase in an escalation step according to the co-occurrence of multiple molecular mechanisms. The mutation of the gyrA gene was the most frequent on codons (Ser83Leu/Thr/Tyr/Trp and Asp87Asn); mutation on the parC gene was the least on codons (Ser80Iso/Leu and Glu84 Val/Gly/Lys). PMQRs genes (4 qnrB ,7 qnrS, and one aac(6’)-Ib-cr) were determined within 15% of the isolates. Allelic variation allows us to report earliest the qnrB81 determinant in an E. coli isolate. Among isolates (35%) belonged to the notorious ST131 lineage. The phylogenetic group showed a predominance of B2 group (51, 25%), however (PFGE) revealed a high level of clonal variability. Worrying incidence of FQs-R E. coli isolates in the rectal flora of our local population showed the potential to cause post-infection. FQ resistance is a complex interplay between mutations in the QRDRs and PMQR determinants that impact MICs. The importance of intestinal microbiota as a reservoir of resistant strains and pandemic clones encourages driving mitigation challenges to characterize molecular mechanisms of antimicrobial resistance to adapt prophylactic therapy, control infection, and ensure epidemiological monitoring.

Abstract Purpose Globally, colorectal cancer (CRC) is among the most prevalent cancers. One distinctive feature of colorectal cancer is its close relationship to the gut microbiota, which is a crucial component of the tumor microenvironment. Over the last ten years, research has demonstrated that colorectal cancer is accompanied with dysbiosis of gut bacteria, fungi, viruses, and Archaea, and that these alterations may be causal. Objectives: This study aimed to evaluate the disruption of the microorganism composition in the intestine, especially bacteria and to determine their relationship with colorectal cancer. Methods An evaluation system for determining colorectal cancer (CRC) risk and prognosis can be established more easily with the help of accurate gut microbiota profiling. Stool samples from 14 CRC patients and 13 controls were collected and the flora relative abundance was measured using targeted quantitative PCR (qPCR) assays to evaluate diagnostic potential of selected biomarkers: Streptococcus gallolyticus and Enterococcus faecalis. Culture and MALDI-TOF mass spectrometry were coupled to identify the gut microbiota in both colorectal cancer and control groups. Results Compared with controls, the gut microbiota of CRC patients showed an increase in the abundance of Enterococcus, Fusobacterium and Streptococcus. At the species level, the CRC enriched bacterium including Escherichia coli, Enterococcus faecalis, Fusobacterium nucleatum, Streptococcus gallolyticus, Flavoni fractorplautii and Eggerthella lenta acted as promising biomarkers for early detection of CRC. Conclusion This study highlights the potential of gut microbiota biomarkers as a promising non-invasive tool for the accurate detection and distinction of individuals with CRC.

Abstract Background The spectrum of Juvenile Idiopathic Arthritis (JIA) in Africa is still largely unknown. We thus set out to illustrate how we set up the PAFLAR JIA registry and describe the clinical profile of Juvenile Idiopathic Arthritis across various regions in Africa. Methods We carried out a retrospective observational cohort study where collaborators were trained on use of the existing PAFLAR REDCAP database to enter data for the JIA patients currently under their care capturing their epidemiological data, clinical features, laboratory investigations, diagnosis and therapy at initial diagnosis. Descriptive statistics including means, standard deviations, medians, interquartile ranges (IQR) for continuous variables and proportions for categorical variables were calculated as appropriate. Tests for difference between groups were performed between categorical variables using Pearson’s chi-square or Fisher’s exact tests. All analyses were performed using SPSS version 22 software. Results We enrolled 302 patients, 58.6% (177 of 302) of whom were female. The median age of disease onset was 7 years (range 3–11 years) and the median age at diagnosis was 8.5 years (range 5–12 years). The median duration delay in diagnosis was 6 months (range 1-20.8 months). The JIA categories included Systemic JIA 18.9% (57), Oligoarticular JIA 19.2% (83), Polyarticular RF + ve 5% (15), Polyarticular RF-ve 17.9% (54), Enthesitis Related Arthritis (ERA) 18.2% (55), Psoriatic Arthritis 7% (21) and undifferentiated JIA 5.6% (17). As regards treatment the commonest therapies were NSAID therapy at 31.1%, synthetic DMARDs at 18.1%, synthetic DMARDs combined with NSAIDs at 17.5% and steroid therapy at 9.6%. Biological DMARDs accounted for 2.3% of therapies offered to our patients at diagnosis. The average JADAS score was 10.3 (range 4.8–18.2) and the average CHAQ score was 1.3 (range 0.7-2.0). Conclusion Our study highlights strategies involved in setting up a Pan-African paediatric rheumatology registry that embraces our broad diversity and the vast spectrum of JIA in Africa while comparing the various therapies available to our patients. The PAFLAR JIA registry strives to ensure a comprehensive representation of the diverse healthcare landscapes within the continent. Further longitudinal observation studies are required to ascertain the long-term outcomes of our patients and ultimately help inform policy to create a more favorable health ecosystem to support the healthcare needs of JIA patients in Africa.

Abstract Background Proteus syndrome (PS) is a complex and uncommon disorder with as its main feature a patchy or mosaic postnatal overgrowth. A high clinical and radiological variability characterizes it. Case presentation We report the case of a 2-year-old boy presenting with lipomas and diagnosed as PS in front of general criteria (sporadic occurrence, progressive course, and mosaic distribution of lesions) and specific criteria (linear epidermal nevus in the chest and asymmetric and overgrowth in the upper limbs) of Biesecker. The course of the disease was marked by a huge overgrowth of arms despite several surgeries. By the age of 10 years, a painful swelling of the right forearm revealed a venous thrombosis on a venous malformation. Conclusions This case report highlights the variability of clinical findings in PS. It also emphasizes the contribution of routine imaging tools for the diagnosis and the follow-up of this rare disease.

In recent years, new concepts such as synchromodality have emerged to help carriers better leverage existing capacities and assets to achieve environmental and socio-economic sustainability. Synchromodality is a vast concept. It involves the intelligent utilization of various transport modes. Its main objective is to enhance the freedom and flexibility to switch between transport modes at transport network nodes. The emergence of synchromodality can be facilitated by optimization and simulation models associated with a sharing web service for decision-making. This article studies the concept of synchromodality in the scientific literature and highlights approaches using simulation and optimization techniques. The major challenge of this study lies in the effective implementation of synchromodality concept in practice, while respecting the instructions and constraints set by freight transport stakeholders from a more generic point of view. For that, we present an implementation of the modal shift on the Seine Axis Corridor. A simulation-optimization framework is proposed to generate reliable transport solutions based on the user preferences and environmental considerations. Finally, we resort to sensitivity analyses to assess the impact of variation of service times.

[This corrects the article DOI: 10.1371/journal.pntd.0001911.].

Pediatric osteoporosis (PO) is a condition that is currently gaining recognition. Due to the lack of official definitions over the past few decades, the exact incidence of PO is unknown. The research does not provide a specific prevalence of PO in different world regions. However, this is expected to change with the latest 2019 guidelines proposed by the International Society of Clinical Densitometry. Although adult osteoporosis (AO) has been postulated a pediatric disease because its manifestation in adulthood is a result of the bone mass acquired during childhood, differences between PO and AO should be acknowledged. AO is defined as low bone density; however, PO is diagnosed based on existing evidence of bone fragility (vertebral fractures, pathological fractures). This is particularly relevant because unlike in adults, evidence is lacking regarding the association between low bone density and fracture risk in children. The enhanced capacity of pediatric bone for reshaping and remodeling after fracture is another difference between the two entities. This contrast has therapeutic implications because medication-free bone reconstitution is possible under certain conditions; thus, background therapy is not always recommended. In this narrative review, differences between PO and AO in definition, assessment, and medical approach were investigated.

Abstract Serine metabolism is involved in various biological processes. Here we investigate primary functions of the phosphorylated pathway of serine biosynthesis in a non-vascular plant Marchantia polymorpha by analyzing knockout mutants of MpPGDH encoding 3-phosphoglycerate dehydrogenase in this pathway. Growth phenotypes indicate that serine from the phosphorylated pathway in the dark is crucial for thallus growth. Sperm development requires serine from the phosphorylated pathway, while egg formation does not. Functional MpPGDH in the maternal genome is necessary for embryo and sporophyte development. Under high CO2 where the glycolate pathway of serine biosynthesis is inhibited, suppressed thallus growth of the mutants is not fully recovered by exogenously-supplemented serine, suggesting the importance of serine homeostasis involving the phosphorylated and glycolate pathways. Metabolomic phenotypes indicate that the phosphorylated pathway mainly influences the tricarboxylic acid cycle, the amino acid and nucleotide metabolism, and lipid metabolism. These results indicate the importance of the phosphorylated pathway of serine biosynthesis in the dark, in the development of sperm, embryo, and sporophyte, and metabolism in M. polymorpha.

The Eucalyptus genus, characterized by its imposing stature and fragrant foliage, has been a source of fascination for humanity over the centuries. The focus of the present investigation was directed towards the essentials oils (EOs) of five Eucalyptus trees cultivated in Tunisia. The GC-MS analysis unveiled unique compositional profiles, a finding substantiated by both Hierarchical Clustering Analysis (HCA) and Principal Component Analysis (PCA) conducted on the leaves EOs. These analyses resulted in the formation of discrete HCA clades, delineating 23 significant components. Notably, the percentage of eucalyptol emerged as the pivotal factor demarcating the separation between three distinct groups. The statistical analysis revealed a dose-dependent relationship in both phytotoxicity evaluation and antibacterial activity. The EOs from Eucalyptus loxophleba and E. salubris exhibited the highest phytotoxicity, inhibiting radical elongation and germination of various seeds, especially Sinapis arvensis and Raphanus sativus. The antimicrobial assessment demonstrated significant inhibitory effects of the EOs on bacterial strains, with MIC values spanning from 14 to exceeding 50 mg/ml. The EOs also affected biofilm formation and cellular metabolism, displaying varied efficacy among different Eucalyptus species against some bacterial strains. The EOs exhibited selective inhibition against acetylcholinesterase (AChE), butyrylcholinesterase (BChE), α-amylase, and α-glucosidase. E. campaspe EO showed the highest AChE activity, while E. loxophleba and E. salubris EOs were most potent toward α-amylase. E. loxophleba EO demonstrated notable activity against α-glucosidase. Overall, these findings provide important data about the diverse biological activities of Eucalyptus EOs, suggesting potential applications in agriculture, medicine, and pharmacy.

Abstract Background Pediatric musculoskeletal disorders account for 10% of first-line consultations in Tunisia. Referral delay and deficiencies in musculoskeletal screening raise a challenge to the early diagnosis and management of rheumatic conditions in children. The pGALS (Pediatric Gait Arms Legs Spine) was developed and translated into many languages to overcome these deficiencies. Our study aimed to adapt and validate pGALS to the Tunisian dialect for school-age children. Methods Using the Delphi method, we carried out a cross-cultural adaptation of the pGALS to the Tunisian dialect. This consensual version was validated in a cross-sectional study, in two pediatric centers. Results Ninety-two patients were enrolled, 43 females (46.7%) and 49 males (53.3%), mean age was 9.4 ± 2.6 years. The mean test duration was 3.4 ± 2.3 min, and the acceptability and comprehension of the test were good. Six patients had a musculoskeletal complaint, 19 had positive pGALS, and 14 were diagnosed with musculoskeletal disease. The internal consistency score (Cronbach’s α) was 0.852. The sensitivity of the test was 92.8%, the specificity was 92.3%, the positive likelihood ratio was 2.16, and the negative likelihood ratio was 0.01. Conclusion The pGALS test adapted to the Tunisian dialect is a relevant, quick, and valid tool for screening musculoskeletal abnormalities in school-age children.

Maryem Ferjani,1 Yosra Zaimi,2 Nouha Trad,2 Yousra Hammi,1 Myriam Ayari,2 Shema Ayadi,2 Taha Sayari,1 Tahar Gargah1 1Department of Pediatrics, Charles Nicolle Hospital, Tunis, Tunisia; 2Department of Gastroenterology, Charles Nicolle Hospital, Tunis, TunisiaCorrespondence: Nouha Trad, Department of Gastroenterology, Charles Nicolle Hospital, Boulevard of April 9, 1938, Bab Saadoun, Tunis, 1007, Tunisia, Tel +216 50858104, Email nouha1med7@gmail.comBackground: Nephrotic syndrome (NS) is associated with a hypercoagulable state and may be complicated by thrombotic events. Venous thrombosis is well-acknowledged, while arterial thrombosis is rather unusual.Case Presentation: We present the case of a 20-year-old woman with a 12-year history of idiopathic NS revealed by extensive cerebral venous thrombosis with pulmonary embolism treated with anticoagulation therapy and oral corticosteroid therapy followed by mycophenolate mofetil (MMF). The thrombophilia assessment did not show any abnormalities. The evolution was marked by the occurrence of several NS relapses controlled by oral corticosteroid therapy until 2017. Subsequently, the patient had not presented a relapse of her disease. The anticoagulant treatment and the MMF were therefore stopped. One year later, the patient presented with severe diffuse acute abdominal pain associated with postprandial vomiting and bilateral lower limb edema. Laboratory results confirmed a NS relapse. An abdominal CT scan revealed acute thrombosis of the superior mesenteric artery with acute mesenteric ischemia. Intraoperative exploration showed mesenteric ischemia with extensive necrosis of the small intestine making their resections incompatible with life. The patient died after 48 hours.Conclusion: Mesenteric arterial thrombosis, which is a rare but life-threatening NS complication, should always be considered, especially in the case of acute non-specific digestive symptoms.Keywords: nephrotic syndrome, mesenteric ischemia, recurrence

Abstract Background Takayasu arteritis is a rare and chronic granulomatous vasculitis that affects the large vessels. Takayasu arteritis targets the aorta and its branches and is still of unknown etiology. It often affects female patients under 50 years of age. A relationship between Takayasu arteritis and tuberculosis has been suggested for a long time. Case presentation We report a severe case of Takayasu arteritis in a 10-year-old Tunisian child revealed by renovascular hypertension with concomitant pulmonary tuberculosis. Conclusions Our patient is among only a few cases of Takayasu arteritis published worldwide affecting young infants and adolescents, which underlines the strong relationship between Takayasu arteritis and tuberculosis.

Background. COVID-19 is the major cause of serious acute respiratory complications, leading to strong perturbation of cytokine release and high levels of interleukin-6. In this work, we assessed the efficacy and safety of Tocilizumab in Tunisian patients with severe COVID-19. Materials and Methods. We enrolled in this retrospective study 255 critically ill patients in the intensive care unit of the military hospital of Tunis. These patients were categorized into a standard group (n = 148) and a Tocilizumab group (n = 107). Medical records were gathered and analyzed between September, 2020 and September, 2021. Results. No significant difference was detected in clinical and biological parameters at admission between the two studied groups. Interestingly, we revealed here a significant improvement in respiratory parameters as well as biological findings such as hemoglobin (p=0.001), platelets (p=0.005), CRP (p=0.0001), fibrinogen (p=0.0001), and creatinine (p=0.002). Regarding the Simplified Acute Physiology Score II and 28-day mortality, we showed a significant decrease of these two parameters following 48 hr of drug administration (p=0.0001, respectively). No significant difference between the two groups regarding complications except the renal failure and the need for renal replacement therapy, which are higher in the standard group as compared to patients treated with Tocilizumab (p=0.02; p=0.0001, respectively). Conclusions. Treatment with TCZ seems to be safe and effective in reducing the mortality rate in severe COVID-19 patients.

Osteogenesis imperfecta (OI) is an inherited skeletal disorder that leads to bone fragility and multiple fractures. Given advances in the genetic understanding of existing phenotypes and newly discovered mutations, therapeutic management of OI has become challenging. Denosumab, a monoclonal antibody that inhibits the interaction between the receptor activator of nuclear factor kappa B ligand (RANKL) and its receptor RANK, has been approved to treat postmenopausal osteoporosis and emerged as an important therapy for malignancies and other skeletal disorders, including pediatric skeletal conditions such as OI. This review summarizes information about denosumab therapy in OI by exploring its mechanisms of action, main indications, and safety and efficacy. Several case reports and small series have been published about the short-term use of denosumab in children with OI. Denosumab was considered a strong drug candidate for OI patients with bone fragility and a high risk of fracture, particularly for patients with the bisphosphonate (BP)-unresponsive OI-VI subtype. The evidence for denosumab's effects in children with OI indicates that it effectively improves bone mineral density but not fracture rates. A decrease in bone resorption markers was observed after each treatment. Safety was assessed by tracking the effects on calcium homeostasis and reporting side effects. No severe adverse effects were reported. Hypercalciuria and moderate hypercalcemia were reported, suggesting that BPs be used to prevent the bone rebound effect. In other words, denosumab can be used as a targeted intervention in children with OI. The posology and administration protocol require more investigation to achieve secure efficiency.

ABSTRACT Cervical tuberculous lymphadenitis (CTL), the most frequent extrapulmonary form of tuberculosis, is a serious health problem in Tunisia. CTL diagnosis is challenging mainly due to the paucibacillary nature of the disease and the potential misdiagnosis as cervical non-tuberculous lymphadenitis (CNTL). Here, we evaluated the performance of heparin-binding hemagglutinin (HBHA) interferon-gamma (IFN-γ) release assay (IGRA) for the diagnosis of CTL. In addition, we evaluated granzyme B, granulysin, and perforin release assays as CTL biomarkers and assessed their potential contribution to improve HBHA-IGRA performance. Peripheral blood mononuclear cells from CTL-suspected patients were stimulated with HBHA, early secreted antigenic target 6 (ESAT-6), or purified protein derivative (PPD) for 24 h in the presence of IL-7. Cytotoxic mediators and IFN-γ release were assessed by enzyme-linked immunosorbent assay. Receiver operating characteristic curves were used to evaluate the capacity of HBHA, ESAT-6, and PPD to discriminate between CTL (n = 27) and CNTL (n = 21). After applying bivariate and multivariate analyses, IFN-γ responses to HBHA appeared to offer the best distinction between CTL and CNTL, with an area under the curve of 0.9947, associated with 95.24% and 100% sensitivity and specificity, respectively. A principal component analysis showed clear clustering of the CTL versus the CNTL groups. This clustering was mainly attributed to HBHA-induced IFN-γ, PPD-induced granzyme B, and PPD-induced IFN-γ. These results thus suggest that the HBHA-IGRA provides high diagnostic accuracy for CTL versus CNTL, with high sensitivity and specificity. Combining HBHA-induced IFN-γ and PPD-induced granzyme B improves the accuracy to identify CTL. IMPORTANCE Cervical tuberculous lymphadenitis (CTL), the most frequent extrapulmonary form of tuberculosis, is currently a major health problem in Tunisia and in several regions around the world. CTL diagnosis is challenging mainly due to the paucibacillary nature of the disease and the potential misdiagnosis as cervical non-tuberculous lymphadenitis. This study demonstrates the added value of the heparin-binding hemagglutinin-interferon-gamma release assay as an immunoassay in the context of CTL.

Introduction Tuberculosis of the soft tissues is a rare form of extra pulmonary tuberculosis, and isolated localization in the popliteal fossa is particularly exceptional. Atypical clinical presentation can lead to delayed diagnosis and serious complications. Case report We report the case of a 17-year-old patient who was diagnosed with tuberculosis of the popliteal fossa. He presented with a painful inflammatory swelling of the right popliteal fossa associated with a homolateral inguinal lymph node, without knee joint effusion. Standard chest and knee X-rays were normal, while MRI showed an 8 cm well vascularized, partly liquefied mass in the popliteal fossa, developed in contact with the semimembranosus and medial gastrocnemius muscles, associated with a popliteal lymph node without synovial effusion or thickening. Microbiological tests did not isolate any germs. The diagnosis was made on histological examination after biopsy, which revealed a caseous granuloma surrounded by epithelioid cells. The patient was treated with anti-tuberculosis therapy for 9 months. The clinical and radiological regression of the swelling was observed without recurrence at 2 years of follow-up. Conclusion Any soft tissue abscess should raise suspicion of tuberculosis, especially in endemic countries. The importance of histopathological examination should be emphasized to establish the diagnosis in the absence of signs in favor of a primary localization.

The present study highlights the influence of support and monomer properties on the performance of thin-film composite (TFC) membranes. For this purpose, a series of polyamide-cellulose acetate thin-film composite nanofiltration (TFC-NF) membranes were prepared by interfacial polymerization technique using cellulose acetate (CA) membrane as support and the monomer of cyclohexane-1,3,5 tricarbonylchloride (HTC) as an organic phase. The effect of the cellulose acetate concentration on the pore size of the membrane support was investigated using 15%, 16.5%, 18%, 19.5%, and 21.5% of cellulose acetate. m-phenylenediamine (MPD), piperazidine (PIP), and 1,3- cyclohexanebis (methylamine) (CHMA) were studied as monomers. Results displayed that PIP/HTC membrane is more hydrophilic and has more intense granular and convex structure with rougher surface compared to the other prepared membranes. The water flow and the porosity depended on the cellulose acetate concentration. The decrease in porosity complied well with permeability, contact angle, and SEM analysis. The membrane performances were evaluated for the retention of NaCl, CaCl2, and Na2SO4 retention. Comparing the Na2SO4 rejection with CaCl2 and NaCl, the former is higher than the latter.

Abstract Background The aim of this study was to compare the effectiveness and safety of ultrasound-guided out-of-plane internal jugular vein (OOP-IJV) and in-plane supraclavicular subclavian vein (IP-SSCV) catheterization in adult intensive care unit. Methods A total of 250 consecutive patients requiring central venous catheterization, were randomly assigned to undergo either ultrasound-guided OOP-IJV or IP-SSCV cannulation. All catheterizations were carried out by three physicians. The primary outcome was the first attempt success rate. Ultrasound scanning time, venous puncture time, insertion time, overall access time, number of puncture attempts, number of needle redirections, success rate, guidewire advancing difficulties, venous collapse and adverse events were also documented. Results The first attempt success rate was significantly higher in IP-SSCV group (83.2%) compared to OOP-IJV group (63.2%) (p = 0.001). The IP-SSCV group was associated with a longer ultrasound scanning time (16.54 ± 13.51 vs. 5.26 ± 4.05 s; p

Introduction Tuberculosis of the soft tissues is a rare form of extra pulmonary tuberculosis, and isolated localization in the popliteal fossa is particularly exceptional. Atypical clinical presentation can lead to delayed diagnosis and serious complications. Case report We report the case of a 17-year-old patient who was diagnosed with tuberculosis of the popliteal fossa. He presented with a painful inflammatory swelling of the right popliteal fossa associated with a homolateral inguinal lymph node, without knee joint effusion. Standard chest and knee X-rays were normal, while MRI showed an 8 cm well vascularized, partly liquefied mass in the popliteal fossa, developed in contact with the semimembranosus and medial gastrocnemius muscles, associated with a popliteal lymph node without synovial effusion or thickening. Microbiological tests did not isolate any germs. The diagnosis was made on histological examination after biopsy, which revealed a caseous granuloma surrounded by epithelioid cells. The patient was treated with anti-tuberculosis therapy for 9 months. The clinical and radiological regression of the swelling was observed without recurrence at 2 years of follow-up. Conclusion Any soft tissue abscess should raise suspicion of tuberculosis, especially in endemic countries. The importance of histopathological examination should be emphasized to establish the diagnosis in the absence of signs in favor of a primary localization.

ABSTRACT: Objectives: This study aims to assess the efficacy of a combination treatment of doxycycline and zinc in the primary prevention of COVID-19 infection in Tunisian health care workers compared with two control groups. Methods: We conducted a prospective, randomized, double-blind clinical trial over 5 months to determine the efficacy of a preventive combination treatment dose of doxycycline (100 mg/day) and zinc (15 mg/day), compared with a single-dose treatment with doxycycline versus placebo. The effectiveness of preventive treatment was measured by the significant decline in the number of cases of COVID-19 infection and/or a decrease in the viral load as determined by SARS-CoV-2 cycle threshold value using reverse transcription polymerase chain reaction tests. Results: We detected a significant decrease of SARS-CoV-2 infection in the group that received both doxycycline and zinc compared with other participants. We also demonstrated that COVID-19 infection was neither associated with diabetes (P = 0.51) nor associated with hypertension (P = 0.99), asthma (P = 0.52), and chronic obstructive pulmonary disease (P = 0.27). Conclusion: Our findings indicated that preventive therapy reduced the risk of SARS-CoV-2. These results suggest that the combination of doxycycline and zinc has a protective effect in patients with SARS-CoV-2 infection.

Objectives: In this article, the authors aimed to review the different tools used in the monitoring of enthesitis-related arthritis. Sources: The authors performed a literature review on PubMed, Google Scholar, and Scopus databases. The dataset included the original research and the reviews including patients with enthesitis-related arthritis or juvenile spondylarthritis up to October 2020. Summary of finding: Enthesitis-related arthritis is a category of juvenile idiopathic arthritis. It is characterized by the presence of enthesitis, peripheral arthritis, as well as axial involvement. The only validated tool for disease activity measurement in juvenile idiopathic arthritis is the Disease Activity Score: It has proven its reliability and sensitivity. Nevertheless, due to an absence of validated evaluation tools, the extent of functional impairment, as well as the children and parents’ perception of the disease, could not be objectively perceived. Despite the great progress in the field of imaging modalities, the role they play in the evaluation of disease activity is still controversial. This is partially due to the lack of validated scoring systems. Conclusions: Further work is still required to standardize the monitoring strategy and validate the outcome measures in enthesitis-related arthritis.

Multiple myeloma is a neoplasm of plasma cells affecting mostly the elderly with incidence peaks between 60 and 70 years. This disease is exceedingly rare in younger people, especially in adults under 30-year-old. Non-secretory multiple myeloma accounts for 1–5% of all cases of multiple myeloma. It is also a rare condition in young adult patients, and only six cases have been reported [1]. We herein describe a rare case of non-secretory myeloma in a 22-year-old male, explaining from chest wall pain, without general manifestation. Plain radiography and CT scans revealed diffuse osteolytic lesion mimicking the Gorham disease. A bone marrow biopsy was conducted, revealing the diagnosis of myeloma.

Background. Immune response plays a crucial role in virus clearance during COVID-19 infection and underpins vaccine efficacy. Herein, we aimed to assess the immune response during COVID-19 infection and following SARS-CoV-2 vaccination. Methods. In this retrospective study, 94 confirmed COVID-19 patients admitted to the intensive care unit were categorized into unvaccinated patients (n = 50), including 33 deceased and 17 discharged patients, and vaccinated group (n = 44) with 26 deceased and 18 discharged patients. Records of patients with severe COVID-19 admitted to the ICU between March, 2021 and March, 2022 were gathered and analyzed. Result. The assessment of immune cell counts revealed a large rise of neutrophils associated to decrease number of lymphocytes in patients with COVID-19 infection. In dead patients, we detected a significant correlation between neutrophils and inflammatory parameters such as IL-6 and CRP. Moreover, analysis of immune cell count following vaccination did not reveal any significant difference. However, the most substantial result, herein, detected is the decrease level of IL-6 in vaccinated patients as compared to unvaccinated. The reduce level of IL-6 following vaccination is observed in discharged patients as compared to deceased. Regarding the level of mortality after vaccination, we showed that all patients who received the first dose were died (46.1%, n = 12) as compared to those who have received two doses (34.6%, n = 9) and the third dose of vaccine (19.23%, n = 3) (p=0.0018). Strikingly, studying the inflammatory parameters after each vaccine dose, we revealed a significant decrease of IL-6 level after the booster dose (third dose), especially in vaccinated discharged patients. Conclusions. Neutrophils combined with IL-6 and CRP can be very useful markers to predict disease severity in patients admitted to ICU. The decrease level of IL-6 in vaccinated group pointed out the impact of vaccination to prevent inflammatory cytokine release.

The regulation of intracellular pyrophosphate (PPi) level is crucial for proper morphogenesis across all taxonomic kingdoms. PPi is released as a byproduct from ~200 metabolic reactions, then hydrolyzed by either membrane-bound (H+-PPase) or soluble pyrophosphatases (PPases). In Arabidopsis, the loss of the vacuolar H+-PPase/FUGU5, a key enzyme in PPi homeostasis, results in delayed growth and a number of developmental defects, pointing to the importance of PPi homeostasis in plant morphogenesis. The Arabidopsis genome encodes several PPases in addition to FUGU5, such as PPsPase1/PECP2, VHP2;1 and VHP2;2, although their significance regarding PPi homeostasis remains elusive. Here, to assess their contribution, phenotypic analyses of cotyledon aspect ratio, palisade tissue cellular phenotypes, adaxial side pavement cell complexity, stomatal distribution, and etiolated seedling length were performed, provided that they were altered due to excess PPi in a fugu5 mutant background. Overall, our analyses revealed that the above five traits were unaffected in ppspase1/pecp2, vhp2;1 and vhp2;2 loss-of-function mutants, as well as in fugu5 mutant lines constitutively overexpressing PPsPase1/PECP2. Furthermore, metabolomics revealed that ppspase1/pecp2, vhp2;1 and vhp2;2 etiolated seedlings exhibited metabolic profiles comparable to the wild type. Together, these results indicate that the contribution of PPsPase1/PECP2, VHP2;1 and VHP2;2 to PPi levels is negligible in comparison to FUGU5 in the early stages of seedling development.

Plant leaves display abundant morphological richness yet grow to characteristic sizes and shapes. Beginning with a small number of undifferentiated founder cells, leaves evolve via a complex interplay of regulatory factors that ultimately influence cell proliferation and subsequent post-mitotic cell enlargement. During their development, a sequence of key events that shape leaves is both robustly executed spatiotemporally following a genomic molecular network and flexibly tuned by a variety of environmental stimuli. Decades of work on Arabidopsis thaliana have revisited the compensatory phenomena that might reflect a general and primary size-regulatory mechanism in leaves. This review focuses on key molecular and cellular events behind the organ-wide scale regulation of compensatory mechanisms. Lastly, emerging novel mechanisms of metabolic and hormonal regulation are discussed, based on recent advances in the field that have provided insights into, among other phenomena, leaf-size regulation.

The novel Schiff base, (E)-4-((2-hydroxybenzylidene)amino)-1,5-dimethyl-2-phenyl-1,2-dihydro-3H-pyrazol-3-one (L1), and its mixed ligand complexes with 2,4,6-tri(pyridin-2-yl)-1,3,5-triazine as an auxiliary ligand (L2) and different transition metal ions (Mn(II), Fe(III), Co(II), Ni(II), Zn(II) and Cd(II)) were synthesised. The 1H NMR spectra of L1 supported their geometrical structures, which was confirmed by X-ray crystallography. The packing of L1 is dominated by H…H, O…H, H…C, C…C, C…N, C…O and N…H interactions. Density functional theory (DFT) calculations showed excellent straight-line correlations between the calculated and experimental geometric parameters where the most stable isomer of L1 is stabilised by an OH…N hydrogen bond, and which agrees with the reported X-ray structure. The prepared complexes were characterised by elemental analyses, molar conductance measurements, IR, UV–vis, and 1H NMR spectroscopic methods. The elemental analysis data suggested a 1:1:1 [M:L1:L2] ratio for all the complexes. The molar conductance measurements of the complexes indicate their electrolytic nature in DMSO as solvent. The electronic absorption spectral data revealed the existence of an octahedral geometry for all complexes.

IntroductionThe Delta variant posed an increased risk to global public health and rapidly replaced the pre-existent variants worldwide. In this study, the genetic diversity and the spatio-temporal dynamics of 662 SARS-CoV2 genomes obtained during the Delta wave across Tunisia were investigated.MethodsViral whole genome and partial S-segment sequencing was performed using Illumina and Sanger platforms, respectively and lineage assignemnt was assessed using Pangolin version 1.2.4 and scorpio version 3.4.X. Phylogenetic and phylogeographic analyses were achieved using IQ-Tree and Beast programs.ResultsThe age distribution of the infected cases showed a large peak between 25 to 50 years. Twelve Delta sub-lineages were detected nation-wide with AY.122 being the predominant variant representing 94.6% of sequences. AY.122 sequences were highly related and shared the amino-acid change ORF1a:A498V, the synonymous mutations 2746T>C, 3037C>T, 8986C>T, 11332A>G in ORF1a and 23683C>T in the S gene with respect to the Wuhan reference genome (NC_045512.2). Spatio-temporal analysis indicates that the larger cities of Nabeul, Tunis and Kairouan constituted epicenters for the AY.122 sub-lineage and subsequent dispersion to the rest of the country.DiscussionThis study adds more knowledge about the Delta variant and sub-variants distribution worldwide by documenting genomic and epidemiological data from Tunisia, a North African region. Such results may be helpful to the understanding of future COVID-19 waves and variants.

Magnesium (Mg2+) is an essential nutrient in all organisms. However, high levels of Mg2+ in the environment are toxic to plants. In this study, we identified the vacuolar-type H⁺-pyrophosphatase, AVP1, as a critical enzyme for optimal plant growth under high-Mg conditions. The Arabidopsis avp1 mutants displayed severe growth retardation, as compared to the wild-type plants upon excessive Mg2+. Unexpectedly, the avp1 mutant plants retained similar Mg content to wild-type plants under either normal or high Mg conditions, suggesting that AVP1 may not directly contribute to Mg2+ homeostasis in plant cells. Further analyses confirmed that the avp1 mutant plants contained a higher pyrophosphate (PPi) content than wild type, coupled with impaired vacuolar H⁺-pyrophosphatase activity. Interestingly, expression of the Saccharomyces cerevisiae cytosolic inorganic pyrophosphatase1 gene IPP1, which facilitates PPi hydrolysis but not proton translocation into vacuole, rescued the growth defects of avp1 mutants under high-Mg conditions. These results provide evidence that high-Mg sensitivity in avp1 mutants possibly resulted from elevated level of cytosolic PPi. Moreover, genetic analysis indicated that mutation of AVP1 was additive to the defects in mgt6 and cbl2 cbl3 mutants that are previously known to be impaired in Mg2+ homeostasis. Taken together, our results suggest AVP1 is required for cellular PPi homeostasis that in turn contributes to high-Mg tolerance in plant cells.