Search

ABSTRACT Background: More than one-third of COVID-19 patients present neurological symptoms ranging from anosmia to stroke and encephalopathy. Furthermore, pre-existing neurological conditions may require special treatment and may be associated with worse outcomes. Notwithstanding, the role of neurologists in COVID-19 is probably underrecognized. Objective: The aim of this study was to report the reasons for requesting neurological consultations by internists and intensivists in a COVID-19-dedicated hospital. Methods: This retrospective study was carried out at Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Brazil, a 900-bed COVID-19 dedicated center (including 300 intensive care unit beds). COVID-19 diagnosis was confirmed by SARS-CoV-2-RT-PCR in nasal swabs. All inpatient neurology consultations between March 23rd and May 23rd, 2020 were analyzed. Neurologists performed the neurological exam, assessed all available data to diagnose the neurological condition, and requested additional tests deemed necessary. Difficult diagnoses were established in consensus meetings. After diagnosis, neurologists were involved in the treatment. Results: Neurological consultations were requested for 89 out of 1,208 (7.4%) inpatient COVID admissions during that period. Main neurological diagnoses included: encephalopathy (44.4%), stroke (16.7%), previous neurological diseases (9.0%), seizures (9.0%), neuromuscular disorders (5.6%), other acute brain lesions (3.4%), and other mild nonspecific symptoms (11.2%). Conclusions: Most neurological consultations in a COVID-19-dedicated hospital were requested for severe conditions that could have an impact on the outcome. First-line doctors should be able to recognize neurological symptoms; neurologists are important members of the medical team in COVID-19 hospital care.

Background: Fifteen percent of small for gestational age are small as a result of fetal growth restriction, which could be due to maternal, placental or fetal factors. It is an important clinical problem associated with increase perinatal mortality and morbidity. Leptin is a protein that produced by many tissues including the placenta (syncytiotropholoast). Dysregulation of leptin metabolism may be implicated in preeclampsia and IUGR pathogenesis. Aim of the study: To study the trend of leptin level alteration in maternal serum and cord blood in pregnancies complicated by fetal growth restriction and its relation with fetal outcome. Methods: An Analytic, cross- sectional study conducted in Al-Elwyia Maternity Teaching Hospital and Alkindy College of Medicine, from October 2009 to June 2010. Sixty seven pregnant women were included and they were divided into two groups: The first group (A) included 34 pregnant women with Intrauterine growth restricted fetuses with and without maternal diseases and the second group (B), included 33 pregnant women with normal pregnancies. Samples from maternal blood and umbilical cord blood were obtained at the time of delivery and leptin level was measured by Enzyme linked immunesorbant assey (ELISA) test. Results:Umbilical cord leptin level was significantly lower in group A (medain1ng/ml) compared with group B (median10.2ng/ml); P

Background: Polycystic ovary syndrome (PCOS) is the most common form of chronic anovulation associated with androgen excess; it occurs in about 5 – 10% 0f reproductive age women. Metabolic syndrome is characterized by insulin resistance, hypertension, obesity, abnormalities of blood clotting and dyslipidemia. Adult women with PCOS have an increased prevalence of the metabolic syndrome(MBS). Objectives: To detect the prevalence of metabolic syndrome in women with proved PCOS, attending the Specialized Center for Endocrinology and Diabetes, in Baghdad. Materials and methods : A total number of 40 women with proved PCOS were included in this study which was conducted in the Specialized Center for Endocrinology and Diabetes-Baghdad, over a period of 5 months(from April till September 2005).In addition to measuring waist circumference and body mass index(BMI),all patients were tested for the levels of C-peptide, Fasting plasma glucose(FPG), Serum luteinizing hormone(LH), Follicle st – imulating hormone(FSH), Prolactin(PRL), Progesterone, estradiol(E2), testosterone,T3,T4 and TSH . Also lipid profile, glycated hemoglobin(HbA1c) were estimated to all patients. Glucose tolerance test(GTT) using 75 gm of glucose was performed on all patients. Results: Out of 40 women with PCOS,eleven patients(27.5%) have impaired GTT. Twenty patients (50%) out of 40 fulfil the criteria of the International Diabetes Fideration(IDF) Consensus Definition of the metabolic syndrome(MBS)-2005. Thirty-Seven patients(92.5%) have a waist circumference more than 80 cm. Thirty-two patients(80%) have secondary amenorrhea. Hirsuitism and increased BMI(body mass index) were present in 33 patients(82.5%) The mean C-peptide level was higher in those patients who had impaired GTT(11 patients),meaning that GTT can be used to detect insulin resistance specially in Labs. where measurements of insulin levels are not available. Conclusions : 1. Metabolic syndrome is present in 50% of our patients,using the IDF Consensus Definition of the metabolic syndrome-2005. 2. Glucose tolerance test can be used to detect the presence of insulin resistance specially in Labs. where measurements of insulin levels are not available. 3. Insulin resistance is present in 27.5% in women with PCOS who were included in our study.

Copyright of Arquivos de Neuro-Psiquiatria is the property of Thieme Medical Publishing Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Competing Interests: Competing interests: None declared.

The bacterium Burkholderia thailandensis produces an arsenal of secondary metabolites that have diverse structures and roles in the ecology of this soil-dwelling bacterium. In coculture experiments, B. thailandensis strain E264 secretes an antimicrobial that nearly eliminates another soil bacterium, Bacillus subtilis strain 168. To identify the antimicrobial, we used a transposon mutagenesis approach. This screen identified antimicrobial-defective mutants with insertions in the hmqA , hmqC , and hmqF genes involved in biosynthesis of a family of 2-alkyl-4(1 H )-quinolones called 4-hydroxy-3-methyl-2-alkenylquinolines (HMAQs), which are closely related to the Pseudomonas aeruginosa 4-hydroxy-2-alkylquinolines (HAQs). Insertions also occurred in the previously uncharacterized gene BTH_II1576 (" hmqL "). The results confirm that BTH_II1576 is involved in generating N -oxide derivatives of HMAQs (HMAQ-NOs). Synthetic HMAQ-NO is active against B. subtilis 168, showing ∼50-fold more activity than HMAQ. Both the methyl group and the length of the carbon side chain account for the high activity of HMAQ-NO. The results provide new information on the biosynthesis and activities of HMAQs and reveal new insight into how these molecules might be important for the ecology of B. thailandensis IMPORTANCE The soil bacterium Burkholderia thailandensis produces 2-alkyl-4(1 H )-quinolones that are mostly methylated 4-hydroxyalkenylquinolines, a family of relatively unstudied metabolites similar to molecules also synthesized by Pseudomonas aeruginosa Several of the methylated 4-hydroxyalkenylquinolines have antimicrobial activity against other species. We show that Bacillus subtilis strain 168 is particularly susceptible to N -oxidated methylalkenylquinolines (HMAQ-NOs). We confirmed that HMAQ-NO biosynthesis requires the previously unstudied protein HmqL. These results provide new information about the biology of 2-alkyl-4(1 H )-quinolones, particularly the methylated 4-hydroxyalkenylquinolines, which are unique to B. thailandensis This study also has importance for understanding B. thailandensis secondary metabolites and has implications for potential therapeutic development., (Copyright © 2020 American Society for Microbiology.)

Background: The incidence of infectious complications has not been previously compared for two types of common urinary catheters used in the long-term care setting: indwelling urethral catheters and suprapubic catheters., Aim: To compare catheter-associated urinary tract infection (CAUTI) rates and multidrug-resistant organism (MDRO) colonization between nursing home residents with indwelling urethral and suprapubic catheters., Methods: Participants included 418 nursing home residents with an indwelling device enrolled in a previously published prospective targeted infection prevention study conducted between 2010 and 2013. Resident age, gender, function, comorbidities, and information on infections, antibiotic use, and recent hospitalizations were obtained at study enrolment, day 14, and every 30 days thereafter for up to one year. Microbiological samples were obtained from several anatomic sites at each visit. Cox proportional hazard models were adjusted for facility-level clustering and other covariates., Findings: In all, 208 study participants had an indwelling urinary catheter, contributing 21,700 device-days; 173 (83%) with a urethral catheter, 35 (17%) with a suprapubic catheter. After covariate adjustment, the suprapubic group had a lower incidence of CAUTI (6.6 vs 8.8 per 1000 device-days; P = 0.05), were half as likely to be hospitalized (hazard ratio (HR) = 0.46; P < 0.01) and were 23% less likely to have had antibiotics in the past 30 days (HR = 0.77; P = 0.02). Among residents catheterized ≥90 days, the mean number of MDROs isolated in the suprapubic group was significantly higher than in the urethral group (0.57 vs 0.44; P = 0.01). Ciprofloxacin-resistant Gram-negative bacilli were frequent in both groups., Conclusion: Residents with a suprapubic catheter may have fewer CAUTIs, less hospitalization and less antibiotic use, but are more likely colonized with MDROs., (Published by Elsevier Ltd.)

The detection of microbial molecules via Toll-like receptors (TLR) in B cells is not well characterized. In this study, we found that both naive and memory B cells lack TLR4 (receptor for LPS) but express TLR9 (receptor for CpG motifs) and produce IL-6, TNF-alpha, and IL-10 upon stimulation with CpG oligonucleotides (ODN), synthetic mimics of microbial DNA. Consistent with the lack of TLR4, purified B cells failed to respond to LPS. Similar to CpG ODN, CD40 ligand (CD40L) alone induced IL-6, TNF-alpha, and IL-10. Production of these cytokines as well as IgM synthesis was synergistically increased when both CpG ODN and CD40L were combined. Unlike IL-6, TNF-alpha, and IL-10, the Th1 cytokine IL-12p70 was detected only when both CpG ODN and CD40L were present, and its induction was independent of B cell receptor cross-linking. CpG ODN did not increase the capacity of CD40L-activated B cells to induce proliferation of naive T cells. However, B cells activated with CpG ODN and CD40L strongly enhanced IFN-gamma production in developing CD4 T cells via IL-12. Together, these results demonstrate that IL-12p70 production in human B cells is under the dual control of microbial stimulation and T cell help. Our findings provide a molecular basis for the potent adjuvant activity of CpG ODN to support humoral immune responses observed in vivo, and for the limited value of LPS.

The vertebrate immune system has evolved a mechanism to detect CpG motifs within microbial DNA (CpG DNA). Synthetic oligonucleotides containing CpG motifs (CpG ODNs) are potent immunomodulatory molecules and outstanding vaccine adjuvants. A number of recent findings have greatly improved our understanding of the biology of CpG DNA, and the immunological effects of CpG DNA are now recognized to be distinct in mouse and human. The plasmacytoid dendritic cell (PDC) was identified to play a pivotal role in mediating CpG-induced immune responses. So far, the B-cell is the only other immune cell subset in humans besides the PDC, equipped with the toll-like receptor-9 to detect CpG motifs. The information on these two prime CpG-sensitive cells has allowed the identification of novel CpG ODNs with distinct functional activity. Together with exciting contributions from animal studies, the way seems to be paved for the successful clinical development of this novel class of molecular therapeutics.

The vertebrate immune system has established TLR9 to detect microbial DNA based on unmethylated CG dinucleotides within certain sequence contexts (CpG motifs). In humans, the expression of toll-like receptor 9 (TLR9) is restricted to B cells and plasmacytoid dendritic cells (PDC). The PDC is characterized by the ability to rapidly synthesize large amounts of type I IFN (IFN-alpha and IFN-beta) in response to viral infection. In contrast to other dendritic cell subsets which express a broad profile of TLRs, the TLR profile in PDC is restricted to TLR7 and TLR9. So far, CpG DNA is the only defined microbial molecule recognized by PDC. An intriguing feature of PDC is its ability to simultaneously produce the two major Th1-inducing cytokines in humans, IFN-alpha and IL-12, both at high levels. The ratio of IFN-alpha versus IL-12 and the quantity of these cytokines are regulated by T helper cell-mediated costimulation via CD40 ligation. The ratio also depends on the differentiation stage of the PDC at the time of stimulation and the type of CpG ODN used. We propose a model in which the establishment of Th1 responses in vivo is improved by appropriately stimulated PDC that otherwise - in the absence of CpG DNA--support Th2 or Th0 responses and thus have been called DC2.

The use of dendritic cells (DC) loaded with tumor antigen is one of the most advanced approaches in cancer immunotherapy. CpG motifs within microbial DNA detected by toll-like receptor 9 are responsible for the favorable properties of CpG oligodeoxynucleotides (ODN) as immune modulators. In this study, mature antigen-pulsed DC or peritumoral injections of CpG ODN, both effective for the treatment of small established tumors, were almost ineffective against large established tumors (1-cm diameter) in a syngeneic murine colon carcinoma model. For large tumors, the antitumor activity of mature antigen-pulsed DC was strongly increased by coinjection of CpG ODN, resulting in a transient control of tumor growth. Rejection of large tumors and long-term cure of mice was achieved by combining injection of antigen-pulsed DC plus CpG ODN at a site distant to the tumor with peritumoral injections of CpG ODN. Depletion of CD8 T cells abrogated the therapeutic activity. Large numbers of DEC-205-positive DC infiltrated the tumor in treated mice. Therapy with 5-fluorouracil and leucovorin was unable to control tumors of the same size. In conclusion, we demonstrate that the immune system, provided that appropriate stimulation with DC and CpG ODN is given, has the potential to cure animals of large solid tumors in situations where even chemotherapy is not efficient.

Epidermal dendritic cells found in inflamed skin include Langerhans cells and the recently identified population of inflammatory dendritic epidermal cells. Another subset of dendritic cells in humans is the plasmacytoid dendritic cell in peripheral blood, which is characterized by the production of large amounts of type I interferon (interferon-alpha and interferon-beta) upon viral infection. We hypothesized that plasmacytoid dendritic cells might be involved in anti-viral defense mechanisms of the skin. Here we investigated plasmacytoid dendritic cells, inflammatory dendritic epidermal cells, and Langerhans cells in epidermal single cell suspensions of normal looking skin from healthy volunteers and of lesional skin from patients with different inflammatory skin diseases. Langerhans cells were found in normal and in inflamed skin samples. In normal skin, plasmacytoid dendritic cells and inflammatory dendritic epidermal cells were low or absent. Lesional skin samples from patients with psoriasis vulgaris and contact dermatitis contained relatively high numbers of both inflammatory dendritic epidermal cells and plasmacytoid dendritic cells. In contrast, many inflammatory dendritic epidermal cells but only very few plasmacytoid dendritic cells could be detected in atopic dermatitis lesions. Lupus erythematosus was characterized by high numbers of plasmacytoid dendritic cells but low numbers of inflammatory dendritic epidermal cells. These results demonstrate that in addition to resident Langerhans cells, plasmacytoid dendritic cells and inflammatory dendritic epidermal cells are selectively recruited to the skin lesions depending on the type of skin disease. The lack of plasmacytoid dendritic cells in atopic dermatitis may predispose atopic dermatitis patients to viral infections such as eczema herpeticum, a secondary infection of atopic dermatitis lesions with herpes simplex virus. The composition of dendritic cell subsets may help to clarify the etiology of inflammatory skin diseases and forms the basis for therapeutic intervention with selective microbial molecules such as immunostimulatory CpG oligonucleotides.

Background: Dendritic cells form a link between innate and acquired immunity. They are capable to detect pathogens based on the recognition of pathogen-associated microbial molecules and trigger the appropriate type of immune responses. In humans, three major subsets of dendritic cells can be distinguished, Langerhans cells of the skin, myeloid DC (MDC) and plasmacytoid DC (PDC). It was reported that PDC infiltrate nasal mucosa in allergen-induced rhinitis. Information about the role of MDC in nasal mucosa and the corresponding mucosa-associated lymphoid tissue, the nasopharyngeal adenoids, is limited., Patients and Methods: : Here we examined the presence of MDC in adenoids and in nasal mucosa of healthy individuals (n = 9) and in patients with allergic rhinitis. MDC were detected by flow cytometry by positive staining for MHC II and CD11c and the lack of lineage markers. Dead cells were excluded from analysis., Results: In adenoids, 0.4 % of all cells were MDC. Considerable numbers of MDC could also be detected in nasal mucosa. No difference was found between healthy individuals and patients with allergies (0.3 % vs. 0.45 % MDC; p = 0.12). Interestingly, MDC were absent in patients who received treatment with glucocorticoids, while very high numbers of MDC were found in patients who recently had upper respiratory tract infections., Conclusion: Our results demonstrate for the first time the presence of MDC in nasal mucosa. MDC numbers were similar in healthy individuals and in patients with allergy. This study forms the basis for examining the role of MDC in the pathogenesis of allergic rhinitis, and for the modulation of MDC functional activity with microbial molecules such as CpG oligonucleotides.