Therapeutic antidepressant potential of a conjugated siRNA silencing the serotonin transporter after intranasal administration.

Major depression brings about a heavy socio-economic burden worldwide due to its high prevalence and the low efficacy of antidepressant drugs, mostly inhibiting the serotonin transporter (SERT). As a result, ~80% of patients show recurrent or chronic depression, resulting in a poor quality of life and increased suicide risk. RNA interference (RNAi) strategies have been preliminarily used to evoke antidepressant-like responses in experimental animals. However, the main limitation for the medical use of RNAi is the extreme difficulty to deliver oligonucleotides to selected neurons/systems in the mammalian brain. Here we show that the intranasal administration of a sertraline-conjugated small interfering RNA (C-SERT-siRNA) silenced SERT expression/function and evoked fast antidepressant-like responses in mice. After crossing the permeable olfactory epithelium, the sertraline-conjugated-siRNA was internalized and transported to serotonin cell bodies by deep Rab-7-associated endomembrane vesicles. Seven-day C-SERT-siRNA evoked similar or more marked responses than 28-day fluoxetine treatment. Hence, C-SERT-siRNA (i) downregulated 5-HT1A-autoreceptors and facilitated forebrain serotonin neurotransmission, (ii) accelerated the proliferation of neuronal precursors and (iii) increased hippocampal complexity and plasticity. Further, short-term C-SERT-siRNA reversed depressive-like behaviors in corticosterone-treated mice. The present results show the feasibility of evoking antidepressant-like responses by selectively targeting neuronal populations with appropriate siRNA strategies, opening a way for further translational studies.

Local allergic rhinitis in children: Clinical characteristics and role of basophil activation test as a diagnostic tool.

BACKGROUND: Local allergic rhinitis (LAR) is a condition involving a localized nasal allergic response in absence of systemic atopy. Most studies on LAR have been performed in adults. We aimed to describe clinical characteristics of LAR pediatric patients, its clinical evolution over a 7-year follow-up period and to study the role of basophil activation test (BAT), for its diagnosis. METHODS: Forty-four children with non-allergic rhinitis (NAR) were included (24 males, 20 females, aged under 15 years). Nasal allergen provocation test (NAPT) and BAT were performed with Dermatophagoides pteronyssinus and Phleum pratense. RESULTS: Seven patients (16%) were diagnosed of LAR. Six reacted to D pteronyssinus and one to P pratense. All LAR and 86% of NAR patients presented perennial symptoms. Fifty-seven percent of NAR and LAR patients referred persistent symptoms. Around half of NAR and LAR patients reported mild-moderate clinical manifestations. Three LAR patients associated conjunctival symptoms, proportionally more than NAR patients (19%, 7 out of 37). NAR patients presented bronchial asthma (n = 10) more frequently than LAR children (n = 1). More than half of LAR and NAR patients presented family history of atopy. BAT was negative in all LAR patients. On follow-up, 3 LAR patients and 10 of the 25 NAR patients who agreed to be retested, presented systemic sensitization. Dust mites were the most frequent allergen involved. CONCLUSIONS: LAR should be ruled out in children with NAR. Almost half of children with LAR develop systemic sensitization over time. BAT shows low sensitivity for the diagnosis of LAR in children.

Multiplex PCR in the empirical antibiotic treatment of patients with SARS-CoV-2 and bacterial respiratory superinfection.

Background: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic led to overuse of antimicrobials, which increased concerns regarding antimicrobial resistance. Objective: To measure the impact of a multiplex polymerase chain reaction (PCR) pneumonia panel on empirical antibiotic treatment for patients with critical coronavirus disease 2019 (COVID-19) with suspected bacterial respiratory superinfection. Methods: This descriptive, prospective study was undertaken in a 36-bed intensive care unit from June 2020 to July 2021. Patients with severe COVID-19 who were ventilated and under suspicion of bacterial respiratory superinfection were included in the study. The intervention was a semi-quantitative multiplex PCR alongside concurrent standard cultures. When PCR panel results were expected to be obtained within 3 h of sampling, empirical antibiotic treatment was not administered while awaiting the results. Otherwise, empirical treatment was initiated. Patients classified as 'avoided empirical treatment' avoided 48-72 h of empirical antibiotic therapy. For those patients who received empirical treatment, the PCR panel results were used to decide whether treatment should be escalated, de-escalated, maintained or stopped. Positive and negative predictive values, and 'avoided empirical treatment' were calculated. Medical conduct and panel results were analysed for patients who received empirical treatment. Results: Eighty-two patients (71% male, 29% female) were included in this study. The mean age was 57.5 years, and the mean APACHE II score was 16. Ninety PCR panels were performed, and the negative and positive predictive values were 99.9% and 66.7%, respectively. Empirical treatment was avoided in 61% of episodes. Of those patients who were receiving antibiotics when the PCR panel was performed, treatment was de-escalated in 71%, escalated in 14%, stopped in 9% and maintained in 6%. A diagnosis of bacterial respiratory superinfection was ruled out in 19% of cases. Conclusions: PCR panels prevented the initiation of empirical antibiotic treatment in two-thirds of patients, and led to de-escalation in more than two-thirds of those who had started empirical antibiotic treatment. The high negative predictive value of the PCR panel allowed the diagnosis of bacterial respiratory superinfection to be ruled out. This tool represents a significant contribution to diagnostic stewardship in order to avoid the unnecessary use of antibiotics.

Pneumocystis jirovecii pneumonia in developing countries.

Pneumocystis pneumonia (PcP) is a serious fungal infection among immunocompromised patients. In developed countries, the epidemiology and clinical spectrum of PcP have been clearly defined and well documented. However, in most developing countries, relatively little is known about the prevalence of pneumocystosis. Several articles covering African, Asian and American countries were reviewed in the present study. PcP was identified as a frequent opportunistic infection in AIDS patients from different geographic regions. A trend to an increasing rate of PcP was apparent in developing countries from 2002 to 2010.

Prevalence of antibodies against Kilham virus in experimental rat colonies of Argentina.

The Kilham rat virus (KRV) is a parvovirus originally isolated from a rat sarcoma in the late 1950s. The clinical signs associated with a natural KRV infection include foetal resorption in dams, runting, ataxia, cerebellar hypoplasia and jaundice in suckling rats, and sudden death, scrotal cyanosis, abdominal swelling and dehydration in juvenile rats. The ability of this virus to produce persistent infections has resulted in a high frequency of contamination of cell cultures and transplantable-tumor system. In addition, the virus may interfere with research in other ways. The remarkable resistance to environmental conditions determines the importance of the detection and control of this agent, especially in the laboratory animal production. This study determines the seroprevalence of Kilham antibodies from sera of adult rats from conventional facilities, using the haemagglutination inhibition test. The seroprevalence varied between 27.8% and 75%. This result confirms that the virus is circulating in Argentinean conventional facilities and might be interfering with research. The recognized Kilham virus may be prevented from supply sources by implementing a health monitoring schedule including a regular serological surveillance, and by keeping the animals under barrier systems.

Hospital environment hygiene nurse: a key player to reduce healthcare associated infections by multi-resistant organisms.

BACKGROUND: Multi-Resistant Organisms (MRO) healthcare-associated infections (HAI) are closely associated with contamination of surfaces. Outsourced companies are usually in charge of both hospital hygiene and environmental hygiene personnel (EHP) supervision, which can result in bias. METHODS: A quasi-experimental study. The intervention was to add the "Hospital Environment Hygiene Nurse" (HEHN). MRO acquired infection rate and MRO acquired colonized rate were calculated, pre and post intervention. Confounding variables: MRO carriage rate upon admission and hospitalisation days median (HDM) were calculated. RESULTS: Median length of stay: 5 days (p=0.85, interquartile range=6 days). Carriage rate upon admission: 4.3% for pre-intervention vs 5.3% post-intervention, dif. (CI 95%): 1% (-1% to 2.9%) p=0.33. MRO acquired infection rate: 4.3% for pre-intervention vs. 2% post-intervention, Standardized Infection Ratio (SIR) (CI 95%): 0.47 (0.25 to 0.87). MRO acquired colonization rate:10.4% for pre-intervention vs. 7.9% post-intervention, SIR (CI 95%): 0.75 (0.53 to 1.07). CONCLUSIONS: As a reinforcement to standard infection control (IC) measures in place, the incorporation of an exclusive, full-time HEHN was significantly useful to reduce MRO HAI.

Late complications of percutaneous tracheostomy using the balloon dilation technique. / Complicaciones tardías de la traqueotomía percutánea con la modalidad de dilatación con balón.

OBJECTIVE: The purpose of this study was to determine the late complications in critically ill patients requiring percutaneous tracheostomy (PT) using the balloon dilation technique. DESIGN: A prospective, observational cohort study was carried out. SCOPE: Two medical-surgical intensive care units (ICU). PATIENTS: All mechanically ventilated adult patients consecutively admitted to the ICU with an indication of tracheostomy. INTERVENTIONS: All patients underwent PT according to the Ciaglia Blue Dolphin® method, with endoscopic guidance. Survivors were interviewed and evaluated by fiberoptic laryngotracheoscopy and tracheal computed tomography at least 6 months after decannulation. VARIABLES: Intraoperative, postoperative and long-term complications and mortality (in-ICU, in-hospital) were recorded. RESULTS: A total of 114 patients were included. The most frequent perioperative complication was minor bleeding (n=20) and difficult cannula insertion (n=19). Two patients had severe perioperative complications (1.7%) (major bleeding and inability to complete de procedure in one case and false passage and desaturation in the other). All survivors (n=52) were evaluated 211±28 days after decannulation. None of the patients had symptoms. Fiberoptic laryngotracheoscopy and computed tomography showed severe tracheal stenosis (>50%) in 2patients (3.7%), both with a cannulation period of over 100 days. CONCLUSIONS: Percutaneous tracheostomy using the Ciaglia Blue Dolphin® technique with an endoscopic guide is a safe procedure. Severe tracheal stenosis is a late complication which although infrequent, must be taken into account due to its lack of clinical expressiveness. Evaluation should be considered in those tracheostomized critical patients who have been cannulated for a long time.

Effect of self-esteem on social interactions during the Ultimatum Game.

Self-esteem is an attitude formed by self-evaluation based on positive and negative aspects of oneself. Low self-esteem is a risk factor for psychiatric disorders and is especially associated with social difficulties. Recently, behavioral economics has allowed the quantitative study of social interactions. We investigated the association between self-esteem and interpersonal problems and whether self-esteem modulates behavior and emotions during an economic task, the Ultimatum Game (UG). In this task participants accept or reject fair/unfair monetary offers from others. Low (LSE, n=40) and high (HSE, n=45) self-esteem participants were assessed in their interpersonal problems and psychiatric symptoms using self-reported questionnaires, and were compared on their decision making and emotional response during the UG. LSE was associated with depression and anxiety symptoms. In addition, LSE was associated with interpersonal problems, especially in the domains of socially inhibited, nonassertive, overly accommodating, self-sacrificing and cold/distant. During the UG, LSE women reported more anger towards unfair offers than HSE women. Our findings suggest that low self-esteem individuals experience high distress by interpersonal problems in several domains. Importantly, low self-esteem in women seems to be associated with an accentuated emotional response to unfair social exchanges. These results may contribute to treat social difficulties in this population.

First Complete Genome Sequences of Zika Virus Isolated from Febrile Patient Sera in Ecuador.

Here, we present the complete genome sequences of two Zika virus (ZIKV) strains, EcEs062_16 and EcEs089_16, isolated from the sera of febrile patients in Esmeraldas City, in the northern coastal province of Esmeraldas, Ecuador, in April 2016. These are the first complete ZIKV genomes to be reported from Ecuador.

Detection of equine herpesvirus 1 genome 1B in Argentina.

To determine the genomic variation of equine herpesviruses (EHVs) isolated in Argentina between 1979 and the first half of 2004, DNA sequences from all 69 strains isolated were analysed. Sixty strains were recovered from aborted fetuses, one from leucocyte-rich plasma from a horse with respiratory signs and eight from cases of neonatal disease. The DNA was extracted from rabbit kidney epithelial (RK13) cells infected with each strain and digested with three restriction endonucleases (BamHI, Bg/II and KpnI). Two strains could be differentiated using BamHI restriction and were assigned to the EHV-1 1B prototype group. Only one of these two strains was typed EHV-1 1B with Bg/II. DNA digestion with KpnI was ineffective. The results obtained in this study demonstrate that the EHV-1 1B genome has been present in Argentina since at least 1996. The finding of two strains with this electropherotype suggests that there is genomic heterogeneity among Argentinian isolates.

The primary structure of rat ribosomal proteins: the amino acid sequences of L27a and L28 and corrections in the sequences of S4 and S12.

The amino acid sequences of rat ribosomal proteins L27a and L28 were deduced from the sequences of nucleotides in recombinant cDNAs and confirmed from the NH2-terminal amino acid sequences of the proteins. L27a contains 147 amino acids (the NH2-terminal methionine is removed after translation of the mRNA) and has a molecular weight of 16 476. Hybridization of the cDNA to digests of nuclear DNA suggests that there are 18-22 copies of the L27a gene. The mRNA for the protein is about 600 nucleotides in length. L27a is homologous to mouse L27a (there are 3 amino acid changes) and to yeast L29. Rat ribosomal protein L28 has 136 amino acids (its NH2-terminal methionine is also processed after translation) and has a molecular weight of 15 707. Hybridization of the cDNA to digests of nuclear DNA suggests that there are 9 or 10 copies of the L28 gene. The mRNA for the protein is about 640 nucleotides in length. L28 contains a possible internal duplication of 9 residues. Corrections are recorded in the sequences reported before for rat ribosomal proteins S4 and S12.

The combination of lithium carbonate and an MAOI in refractory depressions.

Lithium combined with phenelzine alleviated the symptoms of four severely depressed patients. Previously, all four patients had failed to respond to tricyclic antidepressants, and three had not responded to monoamine oxidase inhibitors.

The primary structure of rat ribosomal protein L26.

The amino acid sequence of rat ribosomal protein L26 was deduced from the sequence of nucleotides in a recombinant cDNA and confirmed from the NH2-terminal amino acid sequence of the protein. Rat L26 contains 145 amino acids and has a molecular mass of 17,266 Da. Hybridization of the cDNA to digests of nuclear DNA suggests that there are 8-16 copies of the L26 gene. The mRNA for the protein is about 650 nucleotides in length. Protein L26 has a sequence of 9 residues that may be repeated in three places.

The primary structure of rat ribosomal protein S24.

The amino acid sequence of rat ribosomal protein S24 was deduced from the sequence of nucleotides in a recombinant cDNA. S24 contains 133 amino acids and has a molecular mass of 15,413. Hybridization of the cDNA to digests of nuclear DNA suggests that there are 12-16 copies of the S24 gene. The mRNA for the protein is about 600 nucleotides in length. Rat S24 is homologous to Xenopus laevis S19 and related to Halobacterium morismortui ribosomal protein S15.

The primary structure of rat ribosomal protein S16.

The amino acid sequence of rat ribosomal protein S16 was deduced from the sequence of nucleotides in a recombinant cDNA and confirmed from the NH2-terminal amino acid sequence of the protein. S16 contains 145 amino acids (the NH2-terminal methionine is removed after translation of the mRNA) and has a molecular mass of 16,304. Hybridization of the cDNA to digests of nuclear DNA suggests that there are 11-13 copies of the S16 gene. The mRNA for the protein is about 700 nucleotides in length. Rat S16 is homologous to mouse S16 (there are 2 amino acid changes and a residue is deleted) and related to Halobacterium morismortui ribosomal protein S3 and to Escherichia coli S9.