Dengue, chikungunya, and Zika virus infections in Latin America and the Caribbean: a systematic review.

Objectives: To characterize the distribution profile of dengue, chikungunya, and Zika virus infections in Latin America and the Caribbean and to identify possible factors associated with the risk of dissemination and severity of these arboviruses. Methods: The protocol of this review was registered on the PROSPERO platform. Searches were carried out in the following databases: Virtual Health Library, MEDLINE/PubMed, and Embase. The search terms were: Zika virus, Zika virus infection, dengue, dengue virus, chikungunya virus, chikungunya fever, epidemiology, observational study, Latin America, and Caribbean region. Studies that addressed the distribution of these arboviruses and the risk factors associated with dengue, Zika virus disease, and chikungunya, published between January 2000 and August 2020 in English, Portuguese, and Spanish, were included. Results: Of 95 studies included, 70 identified risk factors, clinical manifestations, and outcomes for arbovirus infections and 25 described complications and/or deaths. The highest frequency of confirmed cases was for dengue. Brazil reported most cases of the three arboviruses in the period analyzed. Environmental and socioeconomic factors facilitated the proliferation and adaptation of vectors, and host-related factors were reported to aggravate dengue. Most deaths were due to chikungunya, Zika virus disease caused most neurological alterations, and dengue resulted in greater morbidity leading to more frequent hospitalization. Conclusions: The review provides a broad view of the three arboviruses and the intrinsic aspects of infections, and highlights the factors that influence the spread of these viruses in the populations studied.

Whole-Body MRI in Limb Girdle Muscular Dystrophy Type R1/2A: Correlation With Clinical Scores.

INTRODUCTION/AIM: The most common limb girdle muscular dystrophy (LGMD) worldwide is LGMD type R1 (LGMDR1). The aim of this study was to correlate the MRI findings with functional scores and to describe the whole-body MRI (WBMRI) pattern in a LGMDR1 Brazilian cohort. METHODS: LGMDR1 patients under follow-up in three centers were referred for the study. Clinical data were collected and a functional evaluation was performed, consisting of Gardner-Medwin and Walton (GMW) and Brooke scales. All patients underwent a WBMRI study (1.5T) with axial T1 and STIR images. Fifty-one muscles were semiquantitatively assessed regarding fatty infiltration and muscle edema. RESULTS: The study group consisted of 18 patients. The highest fatty infiltration scores involved the serratus anterior, biceps femoris long head, adductor magnus, and lumbar erector spinae. There was a latero-medial and caudo-cranial descending gradient of involvement of the paravertebral muscles, with erector spinae being significantly more affected than the transversospinalis muscles (p < 0.05). A striped appearance that has been dubbed the "pseudocollagen sign" was present in 72% of the patients. There was a positive correlation between the MRI score and GMW (Rho:0.83) and Brooke (Rho:0.53) scores. DISCUSSION: WBMRI in LGMDR1 allows a global patient evaluation including involvement of the paraspinal muscles, usually an underestimated feature in the clinical and imaging study of myopathies. Knowledge of the WBMRI pattern of LGMDR1 involvement can be useful in the diagnostic approach and in future studies to identify the best target muscles to serve as outcome measures in clinical trials.

A machine learning proposal method to detect milk tainted with cheese whey.

Cheese whey addition to milk is a type of fraud with high prevalence and severe economic effects, resulting in low yield for dairy products, nutritional reduction of milk and milk-derived products, and even some safety concerns. Nevertheless, methods to detect fraudulent addition of cheese whey to milk are expensive and time consuming, and are thus ineffective as screening methods. The Fourier-transform infrared (FTIR) spectroscopy technique is a promising alternative to identify this type of fraud because a large number of data are generated, and useful information might be extracted to be used by machine learning models. The objective of this work was to evaluate the use of FTIR with machine learning methods, such as classification tree and multilayer perceptron neural networks to detect the addition of cheese whey to milk. A total of 520 samples of raw milk were added with cheese whey in concentrations of 1, 2, 5, 10, 15, 20, 25, and 30%; and 65 samples were used as control. The samples were stored at 7, 20, and 30°C for 0, 24, 48, 72, and 168 h, and analyzed using FTIR equipment. Complementary results of 520 samples of authentic raw milk were used. Selected components (fat, protein, casein, lactose, total solids, and solids nonfat) and freezing point (°C) were predicted using FTIR and then used as input features for the machine learning algorithms. Performance metrics included accuracy as high as 96.2% for CART (classification and regression trees) and 97.8% for multilayer perceptron neural networks, with precision, sensitivity, and specificity above 95% for both methods. The use of milk composition and freezing point predicted using FTIR, associated with machine learning techniques, was highly efficient to differentiate authentic milk from samples added with cheese whey. The results indicate that this is a potential method to be used as a high-performance screening process to detected milk adulterated with cheese whey in milk quality laboratories.

[Clinical characteristics of children infected with different subtypes/genotypes of human respiratory syncytial virus in Beijing from 2009 to 2017].

Objective: To explore the different clinical characteristics of children infected with different subtype/genotype of human respiratory syncytial virus (HRSV) in Beijing. Methods: Respiratory specimens for positive HRSV were randomly collected from children with acute respiratory tract infection (ARTI) in the epidemic season of HRSV from November of each year to January of the next year during 2009 and 2017. G genes of HRSV were amplified and sequenced for subtyping and genotyping by bioinformatics analysis. Clinical data were collected and analyzed. Results: Out of 590 children, 376 (63.7%) with subtype A, and 214 (36.3) with subtype B. The annual dominant subtypes of HRSV from 2009 to 2017 were B-A-A-B-AB-A-A-B-A, respectively, whilst a total of 10 genotypes were detected with 95.8% assigned to genotype ON1 and NA1 of subtype A, and genotype BA9 of subtype B. Children infected with subtype B (96 cases, 44.9%) were more likely aged 0-3 month old than those with subtype A (118 cases, 31.4%) (P=0.001), and more likely to be admitted to Intensive Care Unit(ICU) ((124 cases, 57.9%) than those with subtype A (172 cases, 45.7%)) (P=0.005). Statistical significance were shown among children infected with genotype ON1, NA1 or BA9, in the possibility of infection in children aged 0-3 month (P=0.003), proportion of admission into ICU (P=0.007), length of stay in hospital (P=0.001), and clinical outcome (P=0.001), respectively. Conclusion: Children infected with different subtype or genotype of HRSV have different clinical characteristics, which stresses the important role of the monitoring HRSV subtypes and genotypes among children.

Vitamin D receptor (VDR) gene polymorphisms and expression profile influence upon the immunological imbalance in Turner syndrome.

PURPOSE: Turner syndrome (TS) patients display considerable immune misregulation, and it is hypothesized that Vitamin D (VTD) activity may fluctuate according to Vitamin D receptor (VDR) polymorphisms and/or expression profile. To uncover a possible relationship between VDR genotype and clinical conditions in TS patients, we investigated two functional VDR variants (Cdx-2 and FokI) for allele and genotype frequencies, as well as expression profile in TS individuals versus healthy controls (HC). METHODS: We performed a genetic association study including 100 TS patients and 116 HC. Genotyping for VDR Cdx-2 G > A (rs11568820) and FokI C > T (rs2228570) was performed using Taqman Genotyping Assays. VDR gene expression was also evaluated in 15 TS and 15 HC, using fluorogenic probes by qPCR. Statistical analyses were performed using nonparametric Mann-Whitney test, with a 5% significance level (p < 0.05) to uncover differences between groups. In addition, we investigated whether shifted VDR mRNA levels were associated with Cdx-2 and FokI variants in TS patients. RESULTS: We detected a significantly higher frequency of T allele (p = 0.006) as well as T/T genotype (p = 0.01) for FokI in TS patients when compared to HC. When assessing VDR expression, we identified a downregulation in TS woman (- 2.84 FC) versus HC (p < 0.001). Furthermore, C/T (11.24 FC; p = 0.01) and T/T (9.20 FC; p = 0.01) FokI genotypes were upregulated when compared to C/C reference genotype. CONCLUSION: TS patients show different distribution of FokI polymorphism. Downregulation of VDR gene expression may contribute to immunological imbalance in TS.

Experimental Observation of Vacancy-assisted Martensitic Transformation Shift in Ni-Fe-Ga Alloys.

Positron annihilation lifetime spectroscopy is used to experimentally demonstrate the direct relationship between vacancies and the shift of the martensitic transformation temperature in a Ni_{55}Fe_{17}Ga_{28} alloy. The evolution of vacancies assisting the ordering enables shifts of the martensitic transformation up to 50 K. Our results confirm the role that both vacancy concentration and different vacancy dynamics play in samples quenched from the L2_{1} and B2 phases, which dictate the martensitic transformation temperature and its subsequent evolution. Finally, by electron-positron density functional calculations V_{Ni} is identified as the most probable vacancy present in Ni_{55}Fe_{17}Ga_{28}. This work evidences the capability of vacancies for the fine-tuning of the martensitic transformation temperature, paving the way for defect engineering of multifunctional properties.

Retrospective genomic analysis of Vibrio cholerae O1 El Tor strains from different places in India reveals the presence of ctxB-7 allele found in Haitian isolates.

A total of 45 strains of Vibrio cholerae O1 isolated from 10 different places in India where they were associated with cases of cholera between the years 2007 and 2008 were examined by molecular methods. With the help of phenotypic and genotypic tests the strains were confirmed to be O1 El Tor biotype strains with classical ctxB gene. Polymerase chain reaction (PCR) analysis by double - mismatch amplification mutation assay PCR showed 16 of these strains carried the ctxB-7 allele reported in Haitian strains. Sequencing of the ctxB gene in all the 45 strains revealed that in 16 strains the histidine at the 20th amino acid position had been replaced by asparagine and this single nucleotide polymorphism did not affect cholera toxin production as revealed by beads enzyme-linked immunosorbent assay. This study shows that the new ctxB gene sequence was circulating in different places in India. Seven representatives of these 45 strains analysed by pulsed - field gel electrophoresis showed four distinct Not I digested profiles showing that multiple clones were causing cholera in 2007 and 2008.

Secondary Metabolic Profiles of Two Cultivars of Piper nigrum (Black Pepper) Resulting from Infection by Fusarium solani f. sp. piperis.

Bragantina and Cingapura are the main black pepper (Piper nigrum L.) cultivars and the Pará state is the largest producer in Brazil with about 90% of national production, representing the third largest production in the world. The infection of Fusarium solani f. sp. piperis, the causal agent of Fusarium disease in black pepper, was monitored on the cultivars Bragantina (susceptible) and Cingapura (tolerant), during 45 days' post infection (dpi). Gas Chromatography-Mass spectrometry (GC-MS) analysis of the volatile concentrates of both cultivars showed that the Bragantina responded with the production of higher contents of α-bisabolol at 21 dpi and a decrease of elemol, mostly at 30 dpi; while Cingapura displayed an decrease of δ-elemene production, except at 15 dpi. The phenolic content determined by the Folin Ciocalteu method showed an increase in the leaves of plants inoculated at 7 dpi (Bragantina) and 7-15 dpi (Cingapura); in the roots, the infection caused a phenolic content decrease in Bragantina cultivar at 45 dpi and an increase in the Cingapura cultivar at 15, 30 and 45 dpi. High Performance Liquid Chromatography-Mass spectrometry (HPLC-MS) analysis of the root extracts showed a qualitative variation of alkamides during infection. The results indicated that there is a possible relationship between secondary metabolites and tolerance against phytopathogens.

A review on host-pathogen interactions: classification and prediction.

The research on host-pathogen interactions is an ever-emerging and evolving field. Every other day a new pathogen gets discovered, along with comes the challenge of its prevention and cure. As the intelligent human always vies for prevention, which is better than cure, understanding the mechanisms of host-pathogen interactions gets prior importance. There are many mechanisms involved from the pathogen as well as the host sides while an interaction happens. It is a vis-a-vis fight of the counter genes and proteins from both sides. Who wins depends on whether a host gets an infection or not. Moreover, a higher level of complexity arises when the pathogens evolve and become resistant to a host's defense mechanisms. Such pathogens pose serious challenges for treatment. The entire human population is in danger of such long-lasting persistent infections. Some of these infections even increase the rate of mortality. Hence there is an immediate emergency to understand how the pathogens interact with their host for successful invasion. It may lead to discovery of appropriate preventive measures, and the development of rational therapeutic measures and medication against such infections and diseases. This review, a state-of-the-art updated scenario of host-pathogen interaction research, has been done by keeping in mind this urgency. It covers the biological and computational aspects of host-pathogen interactions, classification of the methods by which the pathogens interact with their hosts, different machine learning techniques for prediction of host-pathogen interactions, and future scopes of this research field.

Clinical evaluation of purified Shilajit on testosterone levels in healthy volunteers.

Purified Shilajit, an Ayurvedic rasayana, was evaluated in healthy volunteers of age between 45 and 55 years for its effect on male androgenic hormone viz. testosterone in a randomised, double-blind, placebo-controlled clinical study at a dose of 250 mg twice a day. Treatment with Shilajit for consecutive 90 days revealed that it has significantly (P < 0.05) increased total testosterone, free testosterone and dehydroepiandrosterone (DHEAS) compared with placebo. Gonadotropic hormones (LH and FSH) levels were well maintained.

Supplementation with live Saccharomyces cerevisiae boulardii during the initial 42 days of the feedlot phase in Nellore beef cattle.

This study aimed to assess the effect of Saccharomyces cerevisiae boulardii CNCM I-1079 supplementation during the initial feeding period on the performance of Nellore bulls in a feedlot system. One hundred ninety-eight Nellore bulls were used in a completely randomized block design, with blocking based on weight within each treatment group: light (331.4 kg; 4 pens), medium (349.7 kg; 4 pens), and heavy (362.5 kg; 3 pens). The treatments included CON-a basal diet, and SCB-basal diet plus a probiotic (Saccharomyces cerevisiae boulardii CNCM I-1079; 1.0 × 1010 CFU/head/d). Experimental diets were administered for the first 42 d (21 d in the step-up phase and 21 d in the finishing diet -870 g concentrate/kg dry matter [DM]). Subsequently, both treatment groups were transitioned to the same basal diet for an additional 76 d, completing 118 d on feed. Linear regression analysis was conducted for dry matter intake (DMI) data. During the initial 42 d, DMI tended to be higher for SCB (P = 0.09); also bulls fed SCB reached the plateau of the curve at 9.17 kg DMI/d earlier (39 d, R2 = 0.97) than those fed CON (43 d; R2 = 0.96) diets. For the first 42 d, the SCB treatment exhibited higher final weight (393.0 vs. 401.4 kg, P = 0.02), total gain (49.3 vs. 53.5 kg, P = 0.02), daily weight gain (1.124 vs. 1.274 kg, P = 0.02), and G:F (0.174 vs. 0.188, P = 0.04). Over the entire 118-d period, SCB-fed bulls had greater final body weight (509.5 vs. 518.0 kg, P = 0.02), total body weight gain (163.7 vs. 170.3 kg, P = 0.01), and average daily gain (1.366 vs. 1.420 kg, P = 0.01). The feed efficiency of SCB-supplemented bulls was 8.05% higher than CON (P = 0.04), and the final carcass weight was 1.69% greater for animals fed SCB (283.8 vs. 288.6 kg, P = 0.04). Total carcass weight gain (110.9 vs. 114.7 kg) and daily carcass weight gain (0.924 vs. 0.956 kg) tended (P = 0.06) to increase by 3.46% in SCB-fed animals compared with those fed CON. Gain yield, carcass conversion, and carcass yield did not differ between treatments. There were no significant differences in the apparent digestibility of DM, crude protein, neutral detergent fiber, and ether extract between treatments. However, starch digestibility (92.7% vs. 88%) was greater for the control treatment (P < 0.001). Including live Saccharomyces cerevisiae boulardii yeast as a probiotic supplement during the initial 42 d in the feedlot enhanced early-stage growth performance in Nellore bulls. Notably, this supplementation carried over carcass gain over the entire feedlot period.

Defining new guidelines for screening the 22q11.2 deletion based on a clinical and dysmorphologic evaluation of 194 individuals and review of the literature.

The 22q11.2 deletion is the most frequent interstitial deletion in humans and presents a wide phenotypic spectrum, with over 180 clinical manifestations described. Distinct studies have detected frequencies of the deletion ranging from 0 % to 75 %, depending on the studied population and selection criteria adopted. Due to the lack of consensus in this matter, several studies have been conducted aiming to define which patients would be eligible for screening; however, the issue is still up for debate. In order to contribute to the delineation of possible clinical and dysmorphologic guidelines to optimize decision making in the clinical setting, 194 individuals with variable features of the 22q11.2 deletion syndromes (22q11.2DS) were evaluated. Group I, clinical suspicion of 22q11.2DS with palatal anomalies; Group II, clinical suspicion without palatal anomalies; Group III, cardiac malformations associated with the 22q11.2DS; and Group IV, juvenile-onset schizophrenia. Multiplex ligation-dependent probe amplification was used for screening the 22q11.2 deletion, which was detected in 45 patients (23.2 %), distributed as such: Group I, 35/101 (34.7 %); Group II, 4/18 (22.2 %); Group III, 6/52 (11.5 %); and Group IV, 0/23 (0 %). Clinical data were analyzed by frequency distribution and statistically. Based on the present results and on the review of the literature, we propose a set of guidelines for screening patients with distinct manifestations of the 22q11.2DS in order to maximize resources. In addition, we report the dysmorphic features which we found to be statistically correlated with the presence of the 22q11.2DS.

Skewed X-chromosome Inactivation in Women with Idiopathic Intellectual Disability is Indicative of Pathogenic Variants.

Intellectual disability (ID) is an early onset impairment in cognitive functioning and adaptive behavior, affecting approximately 1% of the population worldwide. Extreme skewing of X-chromosome inactivation (XCI) can be associated with ID phenotypes caused by pathogenic variants in the X chromosome. We analyzed the XCI pattern in blood samples of 194 women with idiopathic ID, using the androgen receptor gene (AR) methylation assay. Among the 136 patients who were informative, 11 (8%) presented with extreme or total XCI skewing (≥ 90%), which was significantly higher than expected by chance. Whole-exome data obtained from these 11 patients revealed the presence of dominant pathogenic variants in eight of them, all sporadic cases, resulting in a molecular diagnostic rate of 73% (8/11 patients). All variants were mapped to ID-related genes with dominant phenotypes: four variants in the X-linked genes DDX3X (an XCI escape gene; two cases), WDR45, and PDHA1, and four variants in the autosomal genes KCNB1, CTNNB1, YY1, and ANKRD11. Three of the autosomal genes had no obvious correlation with the observed XCI skewing. However, YY1 is a known transcriptional repressor that acts in the binding of the XIST long noncoding RNA on the inactive X chromosome, providing a mechanistic link between the pathogenic variant and the detected skewed XCI in the carrier. These data confirm that extreme XCI skewing in females with ID is highly indicative of causative X-linked pathogenic variants, and point to the possibility of identifying causative variants in autosomal genes with a XCI role.

Green synthesis of gold nanoparticles modulates lipopolysaccharide-induced lung inflammation in Wistar rats.

This study aimed to investigate the effect of intranasal treatment of gold nanoparticles (GNPs) and Curcumin (Cur) on the lipopolysaccharide (LPS)-induced acute pulmonary inflammatory response. A single intraperitoneal injection of LPS (0.5 mg/Kg) was performed, and the animals in the Sham group were injected with 0.9% saline. Treatment was daily intranasally with GNPs (2.5 mg/L), Cur (10 mg/kg) and GNP-Cur started 12 h after LPS administration and ended on the seventh day. The results show that the treatment performed with GNP-Cur was the most effective to attenuate the action of pro-inflammatory cytokines, and a lower leukocyte count in the bronchoalveolar lavage, in addition to positively regulating anti-inflammatory cytokines in relation to other groups. As a result, it promoted an oxirreductive balanced environment in the lung tissue, providing a histological outcome with a reduction in inflammatory cells and greater alveolar area. The group treated with GNPs-Cur was superior to the other groups, with better anti-inflammatory activity and reduced oxidative stress, resulting in less morphological damage to lung tissue. In conclusion, the use of reduced GNPs with curcumin demonstrates promising effects in the control of the acute inflammatory response, helping to protect the lung tissue at the biochemical and morphological levels.

[Clinical characteristics of human adenovirus infection in hospitalized children with acute respiratory infection in Beijing].

Objective: To compare the clinical characteristics of different types of human adenovirus (HAdV) infection in hospitalized children with acute respiratory infection in Beijing, and to clarify the clinical necessity of adenovirus typing. Methods: In a cross-sectional study, 9 022 respiratory tract specimens collected from hospitalized children with acute respiratory infection from November 2017 to October 2019 in Affiliated Children's Hospital, Capital Institute of Pediatrics were screened for HAdV by direct immunofluorescence (DFA) and (or) nucleic acid detection. Then the Penton base, Hexon and Fiber gene of HAdV were amplified from HAdV positive specimens to confirm their HAdV types by phylogenetic tree construction. Clinical data such as laboratory results and imaging data were analyzed for children with predominate type HAdV infection using t, U, or χ2 test. Results: There were 392 cases (4.34%) positive for HAdV among 9 022 specimens from hospitalized children with acute respiratory infection. Among those 205 cases who were successfully typed, 131 were male and 74 were female, age of 22.6 (6.7, 52.5) months,102 cases (49.76%) were positive for HAdV-3 and 86 cases (41.95%), HAdV-7, respectively, while 17 cases were confirmed as HAdV-1, 2, 4, 6, 14 or 21. In comparison of clinical characteristics between the predominate HAdV type 7 and 3 infection, significant differences were shown in proportions of children with wheezing (10 cases (11.63%) vs. 25 cases (24.51%)), white blood cell count >15 ×109/L (4 cases (4.65%) vs.14 cases (13.73%)), white blood cell count <5×109/L (26 cases (30.23%) vs.11 cases (10.78%)), procalcitonin level>0.5 mg/L (43 cases (50.00%) vs. 29 cases (28.43%)), multilobar infiltration (45 cases (52.33%) vs.38 cases (37.25%)), pleural effusion (23 cases (26.74%) vs. 10 cases (9.80%)), and severe adenovirus pneumonia (7 cases (8.14%) vs. 2 cases (1.96%)) with χ²=5.11, 4.44, 11.16, 9.19, 4.30, 9.25, 3.91 and P=0.024, 0.035, 0.001, 0.002, 0.038, 0.002, 0.048, respectively, and also in length of hospital stay (11 (8, 15) vs. 7 (5, 13) d, Z=3.73, P<0.001). Conclusions: HAdV-3 and 7 were the predominate types of HAdV infection in hospitalized children with acute respiratory tract infection in Beijing. Compared with HAdV-3 infection, HAdV-7 infection caused more obvious inflammatory reaction, more severe pulmonary symptoms, longer length of hospital stay, suggesting the clinical necessity of further typing of HAdVs.

Dental undergraduate students' ability in the diagnosis of root fractures: Comparative analysis of different imaging methods.

OBJECTIVE: The aim of this study was to evaluate the diagnostic ability of dental undergraduate students to detect horizontal and oblique root fractures (ORFs) using different imaging techniques. MATERIALS AND METHODS: Nine teeth were selected and randomly divided in three groups in order to create a fracture line without fragments separation: control (without fracture), horizontal root fracture (HRF), and ORF. The root fracture was created using perpendicular force and was confirmed by transillumination. A model with two adjacent teeth was created, and different imaging techniques were performed: conventional periapical radiograph; mesially and distally shifted periapical radiographs; cone-beam computer tomography (CBCT). Twenty students that had participation on dental trauma clinic at the year of 2019 were invited to identify root fractures by a five-point scale: (i) fracture definitely not present, (ii) fracture probably not present, (iii) uncertain whether fracture is present or not, (iv) fracture probably present, and (v) fracture definitely present. Data were analyzed by Kappa test for agreement evaluation. RESULTS: Comparing each student to the gold standard, there was a variation in reproducibility and performance from poor to substantial (0.042-0.667). Reproducibility values ranged from poor to good for all periapical radiographs both in the diagnosis of ORF (-0.33-0.667) and in HRF (0-1). CONCLUSIONS: In CBCT images, the students' ability was lower in HRF detection in comparison with the oblique ones. The students showed limited capacity to diagnose root fractures; however when CBCT was used, the performance was more satisfactory than when periapical radiographs were used.

Systolic dysfunction by two-dimensional speckle tracking echocardiography in dogs with parvoviral enteritis.

INTRODUCTION/OBJECTIVES: Parvoviral enteritis (PVE) can cause either primary or secondary myocardial injury; the latter is associated with systemic inflammatory response syndrome and sepsis. Strain (St) and strain rate (SR) are relatively new speckle tracking echocardiographic (STE) variables used to assess myocardial function and are less influenced by preload and volume status than are conventional variables. The aim of this study was to evaluate systolic function in dogs with PVE using two-dimensional STE. ANIMALS: Forty-five client-owned dogs were included. MATERIALS AND METHODS: Dogs were classified into four groups: healthy (n = 9), PVE-mild (n = 15), PVE-severe (n = 13) and PVE-died (n = 8). Left ventricular global and segmental myocardial St and SR were assessed in radial, circumferential and longitudinal axes in the right parasternal transverse and apical 4-chamber views. In the circumferential and longitudinal axes, the value of each segment was determined separately at the endocardial and epicardial levels. RESULTS: Compared to healthy animals, all dogs with PVE showed significantly impaired St and SR values, mainly for PVE-severe and PVE-died groups. Moreover, the lowest SR value was observed in the circumferential axis at the mid-septal epicardial segment in the PVE-died group. For this variable, a cut-off value of 0.95 s-1 demonstrated 100% sensitivity and specificity for distinguishing between PVE-severe and PVE-died groups. CONCLUSIONS: In the present study, all dogs with PVE developed systolic dysfunction, which was more severe in non-survivors. Assessment of St and SR in dogs with PVE might be clinically useful for evaluating haemodynamic status and developing suitable therapeutic strategies to improve prognosis.

Balance alterations and reduction of pedunculopontine cholinergic neurons in early stages of parkinsonism in middle-aged rats.

The purpose of the present study was to investigate balance alterations and the possible role of the cholinergic neurons in the pedunculopontine nucleus (PPN) in the early stages of a progressive animal model of Parkinson's disease (PD). Twenty-eight middle-aged (8-9 months) male Wistar rats received 4 or 10 subcutaneous vehicle (control, CTL) or reserpine (RES) injections (0.1 mg/kg). The animals were submitted to different behavioral tests. Forty-eight hours after the 4th injection, half of the animals of each group (n = 7) were perfused and submitted to immunohistochemical analysis for tyrosine hydroxylase (TH) and choline acetyltransferase (ChAT). The remaining animals (n = 7 per group) were killed 48 h after the 10th injection. RES group presented motor deficits in the catalepsy and open field tests starting at days 12 and 20 of treatment, respectively (only for the animals that received 10 injections). On the other hand, dynamic and static balance changes were observed at earlier stages of RES treatment, starting at days 6 and 4, respectively. At this point of the treatment, there was no decrease in the number of TH immunoreactivity neurons in the substantia nigra pars compacta (SNpc), ventral tegmental area (VTA) and dorsal striatum (DS). However, a decrease was observed in SNpc and dorsal striatum of animals that received 10 injections. In contrast, there was a decrease in the number of ChAT immunoreactive cells in PPN concomitantly to the balance alterations at the early stages of treatment (after 4 RES injections). Thus, by mimicking the progressiveness of PD, the reserpine model made it possible to identify static and dynamic balance impairments prior to the motor alterations in the catalepsy and open field tests. In addition, changes in balance were accompanied by a reduction in the number of ChAT immunoreactive cells in NPP in the early stages of treatment.

Individuals with isolated congenital GH deficiency due to a GHRH receptor gene mutation appear to cope better with SARS-CoV-2 infection than controls.

PURPOSE: Several interactions exist between the GH/IGF axis and the immune system, including effects on innate immunity and humoral and cellular response. Acquired GH deficiency (GHD) has been recently proposed as a risk factor for severity of COVID-19 infections. However, acquired GHD is often associated to other factors, including pituitary tumors, surgery, radiotherapy, and additional pituitary hormones deficits and their replacements, which, together, may hinder an accurate analysis of the relationship between GHD and COVID-19. Therefore, we decided to assess the seroprevalence of SARS-CoV-2 antibodies and the frequency of symptomatic cases of COVID-19 in adults subjects with untreated isolated GHD (IGHD) due to a homozygous null mutation in the GHRH receptor gene. METHODS: A cross-sectional study was carried out in 27 adult IGHD subjects and 27 age- and gender-matched local controls. Interview, physical examination, bio-impedance, hematological and SARS-CoV-2 IgM and IgG antibodies were analyzed. RESULTS: There was no difference in the prevalence of positivity of anti-SARS-CoV-2 IgM and IgG antibodies between the two groups. Conversely, no IGHD individual had a previous clinical diagnosis of COVID-19 infection, while 6 control subjects did (p = 0.023). CONCLUSION: The production of anti-SARS-CoV-2 antibodies was similar between IGHD subjects due to a GHRH receptor gene mutation and controls, but the evolution to symptomatic stages of the infection and the frequency of confirmed cases was lower in IGHD subjects than in GH sufficient individuals.

[Investigation of pathogenic agents causing acute respiratory tract infections in pediatric patients in a children's hospital assigned for case screening in Beijing during the outbreak of COVID-19].

Objective: To investigate the spectrum of pathogenic agents in pediatric patients with acute respiratory infections (ARI) during the outbreak of coronavirus infectious diseases 2019 (COVID-19). Methods: Three groups of children were enrolled into the prospective study during January 20 to February 20, 2020 from Capital Institute of Pediatrics, including children in the exposed group with ARI and epidemiological history associated with COVID-19 from whom both pharyngeal and nasopharyngeal swabs were collected, children in the ARI group without COVID-19 associated epidemiological history and children in the screening group for hospital admission, with neither COVID-19 associated epidemiological history nor ARI. Only nasopharyngeal swabs were collected in the ARI group and screening group. Each group is expected to include at least 30 cases. All specimens were tested for 2019-nCoV nucleic acid by two diagnostic kits from different manufacturers. All nasopharyngeal swabs were tested for multiple respiratory pathogens, whilst the results from the ARI group were compared with that in the correspondence periods of 2019 and 2018 used by t or χ(2) test. Results: A total of 244 children were enrolled into three groups, including 139 males and 105 females, the age was (5±4) years. The test of 2019-nCoV nucleic acid were negative in all children, and high positive rates of pathogens were detected in exposed (69.4%, 25/36) and ARI (55.3%, 73/132) groups, with the highest positive rate for mycoplasma pneumoniae (MP) (19.4%, 7/36 and 17.4%, 23/132, respectively), followed by human metapneumovirus (hMPV) (16.7%, 6/36 and 9.8%, 13/132, respectively). The positive rate (11.8%, 9/76) of pathogens in the screening group was low. In the same period of 2019, the positive rate of pathogens was 83.7% (77/92), with the highest rates for respiratory syncytial virus (RSV) A (29.3%, 27/92), followed by influenza virus (Flu) A (H1N1) (19.6%, 18/92) and adenovirus (ADV) (14.1%, 13/92), which showed significant difference with the positive rates of the three viruses in 2020 (RSV A: χ(2)=27.346, P<0.01; FluA (H1N1): χ(2)=28.083, P<0.01; ADV: χ(2)=7.848, P=0.005) . In 2018, the positive rate of pathogens was 61.0% (50/82), with the highest rate for human bocavirus (HBoV) (13.4%, 11/82) and followed by ADV (11.0%, 9/82), and significant difference was shown in the positive rate of HBoV with that in 2020 (χ(2)=6.776, P=0.009). Conclusions: The infection rate of 2019-nCoV is low among children in Beijing with no family clustering or no close contact, even with epidemiological history. The spectrum of pathogens of ARI in children during the research period is quite different from that in the previous years when the viral infections were dominant. MP is the highest positively detected one among the main pathogens during the outbreak of COVID-19 in Beijing where there is no main outbreak area.