Cardiovascular disease in Alpha 1 antitrypsin deficiency: an observational study assessing the role of neutrophil proteinase activity and the suitability of validated screening tools.

BACKGROUND: Alpha 1 Antitrypsin Deficiency (AATD) is a rare, inherited lung disease which shares features with Chronic Obstructive Pulmonary Disease (COPD) but has a greater burden of proteinase related tissue damage. These proteinases are associated with cardiovascular disease (CVD) in the general population. It is unclear whether patients with AATD have a greater risk of CVD compared to usual COPD, how best to screen for this, and whether neutrophil proteinases are implicated in AATD-associated CVD. This study had three aims. To compare CVD risk in never-augmented AATD patients to non-AATD COPD and healthy controls (HC). To assess relationships between CVD risk and lung physiology. To determine if neutrophil proteinase activity was associated with CVD risk in AATD. Cardiovascular risk was assessed by QRISK2® score and aortic stiffness measurements using carotid-femoral (aortic) pulse wave velocity (aPWV). Medical history, computed tomography scans and post-bronchodilator lung function parameters were reviewed. Systemic proteinase 3 activity was measured. Patients were followed for 4 years, to assess CVD development. RESULTS: 228 patients with AATD, 50 with non-AATD COPD and 51 healthy controls were recruited. In all COPD and HC participants, QRISK2® and aPWV gave concordant results (with both measures either high or in the normal range). This was not the case in AATD. Once aPWV was adjusted for age and smoking history, aPWV was highest and QRISK2® lowest in AATD patients compared to the COPD or HC participants. Higher aPWV was associated with impairments in lung physiology, the presence of emphysema on CT scan and proteinase 3 activity following adjustment for age, smoking status and traditional CVD risk factors (using QRISK2® scores) in AATD. There were no such relationships with QRISK2® in AATD. AATD patients with confirmed CVD at four-year follow up had a higher aPWV but not QRISK2® at baseline assessment. CONCLUSION: aPWV measured CVD risk is elevated in AATD. This risk is not captured by QRISK2®. There is a relationship between aPWV, lung disease and proteinase-3 activity. Proteinase-driven breakdown of elastin fibres in large arteries and lungs is a putative mechanism and forms a potential therapeutic target for CVD in AATD.

Assessing the trophic status of a tropical microtidal estuary applying TRIX and Random Forest - A combined approach.

The present study assessed the trophic status of a medium-sized microtidal estuary, Rushikulya, India using a combination of mutimetric trophic indices (TRIX, TRBIX) and a machine learning approach (Random Forest). A total of 108 samples were considered to build a predictive model for chlorophyll a (Chl a) and 17 response water variables by observing two annual periods (2021-2023) at six sampling sites. Mean values of TRIX (5.04 ± 0.72) and TRBIX (0.17 ± 0.08) reflected that the estuary has a moderate degree of eutrophication with 'good' water quality and 'biomass saturated'. However, the threshold of TRIX represents a transition state from 'moderate' to 'high' eutrophic. Random Forest model reflected that no apparent association between Chl a and water turbidity above 30 NTU and eutrophication in the estuary fluctuated mainly due to PO43--P along with electrical conductivity. Linear statistical correlations showed high correlation between Chl a and conductivity and a negative correlation between Chl a and dissolved oxygen, unlike PO43--P.

Assessment of water quality of Netravathi-Gurupur estuary, India through chemometric approach for fisheries sustainability.

The present study aimed to assess the water quality dynamics (physicochemical properties, nutrient and chlorophyll-a) in the Netravathi-Gurupur estuary, India across the space and seasons and to simplify the complex water quality dataset through a chemometric approach. The results indicated that pH, EC, temperature, alkalinity, salinity, TDS, hardness, chloride and intense mixing of suspended solids, driven by the semidiurnal tides, are the major factors affecting water quality. Spatial heterogeneity and monsoon have profound impact on nutrient distribution revealing the following values (mg l-1): phosphate-P (0.015-0.105), nitrate-N (0.016-0.094), nitrite-N (0.001-0.012), and silicate (1.83-14.50). The estuary was evaluated for suitability for brackish water fisheries. The results indicated fair water quality during pre- and post-monsoon but marginal quality in monsoon, primarily due to dilution associated with reduced salinity. The outcome of this study can be suitably utilized for the sustainable development of estuaries and their feasibility for brackish water fisheries.

Trace metals and pesticides in water-sediment and associated pollution load indicators of Netravathi-Gurupur estuary, India: Implications on coastal pollution.

Various environmental indicators were used to evaluate the water and sediment quality of the Netravathi-Gurupur estuary, India, for trace metals and pesticide pollution. The descended order of studied metal concentrations (µg/L) in the water was Fe (592.71) > Mn (98.35) > Zn (54.69) > Cu (6.64) > Cd (3.24) > Pb (2.38) > Cr (0.82) and in sediment (mg/kg) was Fe (11,396.53) > Mn (100.61) > Cr (75.41) > Zn (20.04) > Cu (12.77) > Pb (3.46) > Cd (0.02). However, pesticide residues were not detected in this estuarine environment. The various metal indexes categorised the water as uncontaminated, whereas contamination factor, enrichment factor, geo-accumulation index, degree of contamination and pollution load index indicated low to moderate sediment contamination. Multivariate statistics showed that the dominance of natural sources of trace metals with little anthropogenic impact. Improvement in water/sediment quality during the study period might be due to COVID-19 imposed lockdown.

Exploring molecular interactions of potential inhibitors against the spleen tyrosine kinase implicated in autoimmune disorders via virtual screening and molecular dynamics simulations.

The spleen tyrosine kinase (Syk) plays a pivotal role in immune cells' signal transduction mechanism. While fostamatinib, an FDA-approved Syk inhibitor, is currently used to treat immune thrombocytopenia, the search for improved Syk-targeted medications to treat autoimmune diseases is still underway. Herein, we screened 38,493 compounds against Syk and selected eight leads based on the docking score and ADMET properties, and performed 3×200 ns long molecular dynamics simulations of the apo and Syk-ligand complexes. We considered R406, the active component of fostamatinib, as a control. The molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) calculations demonstrated the lead1 (ΔGbind = -30.35 kcal/mol) exhibited a similar binding free energy as the control (ΔGbind= -29.82 kcal/mol). The Syk stabilizing effect of lead1 was also indicated in its network features, sampling space, and residual correlation motion analysis. We further generated 100 structural analogues of lead1 using deep learning, and one of the analogues displayed a better binding free energy (ΔGbind= -47.58 kcal/mol) compared to the control or lead1, facilitated by more favourable van der Waals interactions and lesser binding-opposing net polar forces. This analogue may be further exploited to develop effective therapeutics against Syk-associated diseases after validation in vitro and in vivo.

First report of molecular confirmation and phylogenetic analysis of ocular seteriasis in buffalo in India using 12S rRNA.

An adult Indian buffalo (Bubalus bubalis) presented with corneal opacity, irritation, and excessive lacrimation from the left eye in the Referral Veterinary Polyclinic-Teaching Veterinary Clinical Complex (RVC-TVCC), Indian Veterinary Research Institute, Izatnagar. Clinical examination revealed a whitish thread-like worm in the left eye's anterior chamber. The worm was surgically removed from the eye with supportive nerve blocks. Light microscopy was used for parasite morphological identification, which provided insight into the worm as female Setaria sp. Genomic DNA was isolated, and polymerase chain reaction amplification of 12S rRNA was conducted for molecular confirmation of the parasite. The amplicon was sequenced and analysed by bioinformatics software. Sequence data showed an amplicon size of 243 bp. Phylogenetic analysis with reference data from the NCBI Genbank database revealed the worm was S. digitata, with a similarity of 99.17%. The common predilection site of S. digitata is in the peritoneal cavity of natural hosts like cattle and buffalo and is mostly non-pathogenic. The aberrant migration of the parasite larva to the brain and eye commonly occurs in goats, sheep, and horses, causing clinical conditions like cerebrospinal nematodiasis (lumbar paralysis) and ocular setariasis, respectively. Nevertheless, until now, there have been no reports of ocular setariasis in buffalo. This report is the first unusual occurrence of ocular setariasis in buffalo and its molecular confirmation and phylogenetic analysis using 12S rRNA.

Occurrence of canine parvovirus type 2c in diarrhoeic faeces of dogs in Kolkata, India.

Canine parvovirus-2(CPV-2) causes a highly contagious disease of dogs characterised by acute hemorrhagic gastroenteritis, lethargy, vomiting, fever and usually bloody or mucoid diarrhoea. In the present study, 41 faecal samples collected from dogs exhibiting the signs of fever, vomition, bloody or mucoid diarrhoea in Kolkata, India were screened by haemagglutination test and PCR for detection of capsid protein coding VP2 gene. The viral genotype was detected by multiplex PCR and analysis of partial VP2 gene nucleotide sequences of selected PCR products with bioinformatics tool. Thirteen (31.71%) samples were found positive with HA titre ≥ 32 whereas 28 (68.29%) samples were positive by PCR of VP2 gene indicating higher sensitivity of PCR. Highest occurrence of CPV-2 was observed in the age group of 1-6 months (80.65%) and non-descript breeds with no history of vaccination (85%). Three samples were antigenic type CPV-2a, rest were CPV-2b/CPV 2c. Six CPV sequences were found to be highly similar to published CPV 2c sequences in BLAST analysis revealing a maximum identity of 99-100% with other CPV-2c strains and clustered together with CPV-2c strains of India and other countries in phylogenetic analysis. The present study highlights the need for continuous monitoring of samples to detect gradual changes in circulating CPV-2 genotypes in India.

Molecular characterization and serodiagnostic evaluation of the Echinococcus ortleppi recombinant glutaredoxin 1 protein for cystic echinococcosis in buffalo (Bubalus bubalis).

Cystic echinococcosis (CE), caused by the metacestode of Echinococcus granulosus sensu lato (s.l.), adversely affects the physiology of the vital organs in which they grow. Condemnation of meat causes substantial economic loss to the livestock industry. Conventionally the infection is detected by necropsy as serological diagnosis of the infection in livestock is ambiguous. Identification of specific diagnostic antigens would be a substitute for the cyst fluid antigens which lack adequate diagnostic sensitivity and specificity. BLAST analysis supported by the negligible pairwise nucleotide distance of the 389 nt COX1, 489 nt NAD1, and 425 nt ITS1 with the related sequences of E. ortleppi ascertained the association of E. ortleppi with CE in buffaloes. Given the extensive distribution of glutaredoxin 1 in every developmental stage of Echinococcus granulosus s.l that makes it an ideal serodiagnostic antigen for CE, we expressed the 14 kDa E. ortleppi glutaredoxin 1 (rEoGrx1) protein in E. coli BL21 (DE3) and tested a total of 225 sera samples, including 126 sera samples from the necropsy-positive buffalo, by the rEoGrx1 IgG-ELISA. The ELISA could detect a total of 82/126 sera samples as positive. The diagnostic sensitivity and specificity of the rEoGrx1 IgG-ELISA were 65.1 % and 51.5 %, respectively. The protein showed serological cross-reaction against Fasciola gigantica, Toxoplasma gondii, and Sarcocystis sp. The in silico bioinformatics analysis of the E. ortleppi, F. gigantica, and T. gondii glutaredoxin sequences revealed fully conserved amino acids at positions 11 and 21, the substitution of conserved amino acids at positions 14 and 6, and semi-conserved substitutions at positions 3 and 4, respectively. The findings partly explain the molecular basis of the serological cross-reactivity of the protein.

Geochemical distribution and forms of phosphorus in the surface sediment of Netravathi-Gurupur estuary, southwestern coast of India.

Estuaries are the most productive transition ecosystem and phosphorus (P) plays an important role in these ecosystems. Therefore, in the present study, sequential extraction method was used to determine the abundance of five sediment P fractions (calcium (Ca-P), Iron (FeP), aluminum (AlP), exchangeable (Ex-P) and organic (OrgP) bound P) in Netravathi-Gurupur estuary, India. Total phosphorus (TP) content varied from 435-810 mg/kg (non-monsoon) and 258-699 mg/kg (monsoon). Inorganic P was dominant part. Different P fractions followed similar order (Fe-P > Ca-P > Al-P > Org-P > Ex-P) with respect to seasons. FeP was dominant fraction, indicating probable anthropogenic stress. Sediment may act as source of P as bioavailable P constituted 40-69.2 % of TP. Molar ratio of OC to Org-P in sediment indicated terrestrial sources of organic matter. However, the estimated phosphorus pollution index were lower than one except a few cases indicating less ecological risk with respect to sedimentary TP load.

Optimization of external (in air) particle induced gamma-ray emission (PIGE) methodology for rapid, non-destructive, and simultaneous quantification of fluorine, sodium, and phosphorus in nuclear waste immobilization matrices.

External (in air) PIGE methodology has been optimized for rapid quantification of fluorine, sodium, and phosphorus in fluorapatite waste immobilization matrices for Molten Salt Reactor (MSR). The present methodology addresses the issue of distinguishing hydroxyapatite and fluorapatite phases through XRD patterns. Fluctuations in proton beam current have been monitored by prompt γ-ray from nitrogen (2312 keV) through 14N(p,p'γ)14N nuclear reaction and have successfully been applied as a new method of current normalization, for the first time, in external PIGE method with lower Compton background and negligible spectral interference. The proposed method was also compared with the earlier method of current normalization using 165 keV (181T(p,p'γ)181Ta) from the Tantalum window used for obtaining "in air" beam. For the fluctuation of beam current within 5-10 nA, nitrogen from air can be used as an effective current normalizer. Moreover, the uncertainty (within ±3%) was also improved in the present method of current normalization. Fluorine can be estimated from trace to major concentrations using 197 keV (19F(p,p'γ)19F) γ-ray with highest sensitivity as compared to other prompt γ-rays (110 keV and 1236 keV). The matrix effect in PIGE was also eliminated by diluting the sample in cellulose. The method was validated using the synthetic samples (Ca10(PO4)6F2, Na2Eu2Ca6(PO4)6F2, Na1.5Eu1.5Ca7(PO4)6F2, Na1Eu1Ca8(PO4)6F2, Na0.5Eu0.5Ca9(PO4)6F2, and Sr10(PO4)6F2). The results were found to be satisfactory and in good agreement with stoichiometric amounts. Elements such as Na, P, and Ca were determined in the fluorapatite samples using PIGE and EDXRF, respectively, as a part of chemical quality control. Moreover, in external PIGE, 1266 keV γ-ray (31P(p,p'γ)31P) provides more accurate P concentrations in the samples.

Performance of various mathematical functions for the in-situ relative detector efficiency towards its applicability for k0 IM-NAA.

The in-situ relative detection efficiency strongly influences the characteristics of the k0-based internal monostandard neutron activation analysis (IM-NAA). In the present work, various mathematical functions were explored for the establishment of in-situ relative detector efficiency calibration and compared their performance based on the reduced chi-square (χ2) values. Among the various mathematical functions, the polynomial logarithm with 6th order was found to be associated with the minimum mean standard deviation for the experimental data and the lowest value of reduced χ2 after carrying out multiple iterations using Nelder-Mead algorithm. Quality assurance of the function was tested by carrying out elemental quantification of the NIST SRM 1633b coal fly ash. Gamma energies of the activation products, 152mEu, 59Fe, 140La, 24Na and 46Sc of the irradiated NIST standard were used for the in-situ relative full energy peak efficiency calibration of 30% HPGe detector. The sample was counted for different time intervals for the complete profiling of the elements present in the NIST SRM. The deviations for most of the elements were found to be within ±5% with respect to the certified values and ξ-score values were within ±2, demonstrating its better accuracy. This method was also applied satisfactorily to profile the elemental concentrations of alloy materials used in a thermal sensor guide tube of the steam generator in a test reactor.

Metal contaminations in sediment and associated ecological risk assessment of river Mahanadi, India.

Mahanadi is one of the major rivers of peninsular India. Like other Indian rivers, it is contaminated with sewages, industrial discharges, and agricultural runoff. Thus, necessity was felt to monitor its pollution status. Present work was part of that program and aimed to assess the sediment contamination due to the trace metals Cd, Cr, Cu, Mn, Pb, and Zn during 2012-2015. Sediment pollution status and ecological risks were evaluated calculating contamination factor (CF), geo-accumulation (Igeo), pollution load index (PLI), potential ecological risk (EiR), etc. The recorded metal concentrations were Cd BDL of flame mode of AAS; Cr BDL - 73.9; Cu BDL - 44.4; Mn 37.2 - 1887.0; Pb BDL - 29.5; and Zn BDL - 92.5 mg kg-1. As per US EPA guidelines, Cr concentrations at many locations were in the moderately polluted range. Igeo, CF, mCd, PLI, and EiR indicated low pollution levels and low ecological risks due to the trace metals assessed. The sediment quality guidelines (SQGs) indicated that Cr and Cu concentrations exceeded (16% sample) the threshold effect concentrations and may occasionally exhibit adverse biological effects. The association of sediment organic matter, conductivity and content of Cu, and their grouping in component 1 of PCA revealed that the anthropogenic input was dominant and so also the component 2 where Cr exhibited moderately good correlation with organic matter. Cluster analysis of the sampling sites based on pollution status yielded 3 groups: relatively uncontaminated (S3, S4), low to moderately contaminated (S2), and moderately contaminated (S1, S5, S6) stretches.

Guanylin and uroguanylin: a promising nexus in intestinal electrolyte and fluid homeostasis.

Intestinal guanyl peptides like guanylin and uroguanylin are the potent regulators of fluid-ion homeostasis. They are secreted from various cells of the intestinal mucosa, including enterochromaffin cells, epithelial cells, goblet cells, Paneth cells and others. These peptide hormones serve as ligands for receptor guanylyl cyclase-C (GC-C), which produces intracellular cyclic guanosine monophosphate (cGMP) and activates protein kinase G II (PKGII). cGMP/PKGII activates cystic fibrosis transmembrane conductance regulator for anion transport to the intestinal lumen, inhibits Na+/H+ exchanger that restricts H+ secretion and Na+ absorption, resulting in the retention of luminal fluid. These functions maintain intestinal pH, prevents hypernatremia and unwanted hypervolemic shock. Additionally, fluid balance in the intestine preserves the hydrated state of the colonic mucus that influences the growth of the commensal microorganisms and bowel clearance. Moreover, GC-C/cGMP signaling is involved in the regulation of intestinal barrier integrity, epithelial cell renewal, cell cycle, DNA damage repair, inflammatory responses, epithelial-mesenchymal transition and cancer progression. Impairment of GC-C activation causes functional gastrointestinal disorders, inflammatory bowel disease, visceral pain and colorectal cancer, suggesting that oral supplementation of guanyl peptide analogs (linaclotide, plecanatide) may prove useful for the treatment of these diseases.

Melatonin application differentially modulates the enzymes associated with antioxidative machinery and ascorbate-glutathione cycle during arsenate exposure in indica rice varieties.

Arsenic (As) contamination and accumulation in rice is a serious concern causing severe oxidative damage. Melatonin acts as a protective agent in plant defence against multiple abiotic stresses. The mechanism of antioxidant function of melatonin during As stress in rice genotypes is less studied. In this study, hydroponically-grown As-susceptible (Khitish) and As-tolerant (Muktashri) rice cultivars, subjected to 150 µm arsenate stress, were supplemented with exogenously applied melatonin (20 µm) to examine the plant defence mechanism. Melatonin (Mel) increased root and shoot length, fresh and dry weight, chlorophyll a and b content and activated reducing power and free radical scavenging capacity in both rice cultivars. The role of Mel in the sensitive variety appeared to be more prominent with respect to reduced water saturation deficit by reducing endogenous As and H2 O2 accumulation, and enhancing overall antioxidant capacity by imposing reduced requirement of catalase for ROS detoxification, and restoring As-inhibited activity of glutathione-S-transferase, glutathione peroxidase and dehydroascorbate reductase. In contrast, melatonin treatment in the tolerant cultivar required reduced involvement of ascorbate peroxidase to deal with As toxicity, and complemented the stress-mediated inhibition of guaiacol peroxidase activity. Isozyme profiling also established extensive varietal differences with regard to induction of new isoform(s) by Mel during As treatment. This study provides clear insights into mechanistic details of the regulation of antioxidative enzymes by melatonin in contrasting rice genotypes, which may prove helpful in generating As tolerance in susceptible rice varieties grown in marginalized soils, thereby improving crop yield and productivity.

First Observation of Multiple Transverse Wobbling Bands of Different Kinds in

We report the first observation of two wobbling bands in ^{183}Au, both of which were interpreted as the transverse wobbling (TW) band but with different behavior of their wobbling energies as a function of spin. It increases (decreases) with spin for the positive (negative) parity configuration. The crucial evidence for the wobbling nature of the bands, dominance of the E2 component in the ΔI=1 transitions between the partner bands, is provided by the simultaneous measurements of directional correlation from the oriented states ratio and the linear polarization of the γ rays. Particle rotor model calculations with triaxial deformation reproduce the experimental data well. A value of spin, I_{m}, has been determined for the observed TW bands below which the wobbling energy increases and above which it decreases with spin. The nucleus ^{183}Au is, so far, the only nucleus in which both the increasing and the decreasing parts are observed and thus gives the experimental evidence of the complete transverse wobbling phenomenon.

Somatic embryogenesis as an alternative for in vitro multiplication of Butia odorata from mature zygotic embryos.

Butia odorata is a palm native to southern Brazil and Uruguay, not domesticated, much appreciated for its fruits and economic potential. However, the extractivism and the difficulty of propagation have led to the decline of natural populations. The objective of this work was to prove the possibility of induction of somatic embryogenesis in B. odorata. Mature zygotic embryos were induced in two media, MS and Y3, combined with auxin 2,4-D and picloram in five concentrations (2,4-D: 0, 361.99, 452.49, 542.99 and 633.48 µM/L, picloram: 0, 50, 150, 300 and 450 µM/L). The results promising during induction with the formation of embryogenic calli and somatic embryos, however the regeneration of them was not efficient, this may be due to the occurrence of somatic embryos fused during its development. The roots were formed, but the aerial part remained molten, not completing its development. Auxin picloram and Y3 medium provided the most adequate conditions for calogenesis, formation of embryogenic callus and somatic embryos, with concentrations of 150, 300 and 450 µM/L. This is the first description of somatic embryogenesis in B. odorata that will serve as the basis for future research and adjustments of the methodology proposed here.

Clinical management of dogs with presumptive diagnosis of cervical intervertebral disc disease: 78 cases (2006-2017) / Tratamento clínico de cães com diagnóstico presuntivo de doença do disco intervertebral cervical: 78 casos (2006-2017)

This study aimed to identify dogs with a presumptive diagnosis of cervical intervertebral disc disease (IVDD; C1-C5 or C6-T2) submitted to clinical management and evaluate the outcome. This study also aimed to demonstrate the age, sex, and treatment response according to the neurological degree, and verify whether those factors could potentially influence the outcome. The data were obtained from patients with a neurological dysfunction, admitted at the Veterinary Hospital from January 2006 to March 2017. In addition to patient records, the tutors answered a questionnaire related to the success of therapy. A hundred and seventy-seven neurological records were evaluated, and 78 were included in the study according to the inclusion criteria. The most frequent breeds were Dachshunds, followed by mixed-breed dogs. Regarding the neurological dysfunction degree, 58.97% presented grade I (only neck pain), 25.64% were grade II (ambulatory tetraparesis), and 15.38% grade III (nonambulatory tetraparesis). Absolute and partial space rest were performed in 75.64% and 24.36% of the cases, respectively. The minimum rest time was one week and could come up to four weeks. Most dogs were small-sized (≤15kg). The recovery was satisfactory in 87.17% of dogs and unsatisfactory in 12.83%. Regarding recurrence, we observed that 10.3% of dogs presented satisfactory recovery. The clinical treatment for dogs with cervical IVDD can be indicated with adequate clinical response to dysfunction degrees ranging from I to III, either at rest or in restricted space and with a low rate of relapse.(AU)

O objetivo desse estudo foi identificar cães com diagnóstico presuntivo de doença do disco intervertebral cervical (DDIV; C1-C5 ou C6-T2) submetidos ao tratamento clínico e avaliar a resposta a terapia instituída e o índice de recidiva. Esse estudo também visou demonstrar a idade, o gênero e a resposta ao tratamento de acordo com o grau neurológico, a fim de verificar se esses parâmetros podem ser utilizados como fatores prognósticos para a evolução clínica desses pacientes. Foram revisados os registros neurológicos do Hospital Veterinário Universitário de janeiro de 2006 a março de 2017. Realizaram coleta de dados a partir dos registros e por meio de um questionário respondido pelos tutores. Avaliaram 177 fichas neurológicas de cães e obtidas informações para inclusão no estudo em 78 delas. As raças mais frequentes foram Dachshunds, seguido dos cães sem raça definida. Quanto ao grau de disfunção neurológica, 58,97% apresentavam grau I (somente dor), 25,64% estavam em grau II (tetraparesia ambulatória) e 15,38% em grau III (tetraparesia não ambulatória). O repouso absoluto e em espaço restrito foram realizados em 75,64% e 24,36% dos casos, respectivamente e com duração de no mínimo uma semana, podendo chegar a mais de quatro semanas. A maioria dos animais era de pequeno porte (≤15kg). A recuperação foi satisfatória em 87,17% dos cães e insatisfatória em 12,83%. Quanto à recidiva, esta foi observada em 10,3% dos pacientes com recuperação satisfatória. O tratamento clínico para cães com DDIV cervical pode ser indicado com adequada resposta clínica para graus de disfunção que variam de I a III, seja em repouso absoluto ou em espaço restrito e com baixo índice de recidiva.(AU)

Low-dose curcumin-loaded Eudragit L-100-nanocapsules in the diet of dairy sheep increases antioxidant levels and reduces lipid peroxidation in milk.

The main objective of this study was to evaluate whether the addition of curcumin-loaded nanocapsules (prepared and characterized) in the diets of dairy sheep improved milk quality. The nanocapsules were prepared using two polymers: poly-ε-caprolactone (PCL) and Eudragit L-100. The nanocapsules contained 0.25 mg/ml (Nano-Eudragit L-100) and 2 mg/ml (Nano-PCL) of curcumin. Dairy sheep were divided into four groups: A (control), B (30 mg free curcumin/kg concentrate), C (3 mg Nano-PCL/kg concentrate), and D (3 mg Nano-Eudragit/kg concentrate). We observed that the number of total leukocytes and serum globulin levels were lower in Group D than in the control (Group A) (p < 0.05). Antioxidant capacity against peroxyl radicals (ACAP) and catalase enzymes was elevated in Group D, with consequently reduced lipid peroxidation (LPO; p < 0.05). In milk, there were no differences in production and composition between groups during the experimental period (p > 0.05); however, ACAP increased and LPO decreased in milk. PRACTICAL APPLICATIONS: Curcumin is a functional molecule with potent antioxidant, anti-inflammatory, and antimicrobial actions, used frequently and with medical indications in human food. Free curcumin in sheep diets improves milk quality and increases its shelf life. This study showed that curcumin nanocapsules produced from the Eudragit L-100 polymer potentiated the anti-inflammatory and antioxidant actions of dairy sheep when used in the diet daily, at doses 10 times lower than that of free curcumin. These positive effects were reflected in higher total antioxidant capacity and lower lipid peroxidation in milk in sheep-fed curcumin-loaded Eudragit L-100 nanocapsules, generating desirable milk properties. In practice, the use of nanotechnology enhances the beneficial effects of curcumin in milk, possibly creating a nutraceutical food desirable to consumers.

Association of urinary sodium/potassium ratio with structural and functional vascular changes in non-diabetic hypertensive patients.

Studies aiming to associate the sodium/potassium (Na/K) ratio with hypertension use 24-hour urinary excretion as a daily marker of ingestion. The objective of this study was to evaluate the association between urinary Na/K ratio and structural and functional vascular alterations in non-diabetic hypertensive patients. In hypertensive patients (n = 72), aged between 40 and 70 years, both sexes (61% women), in use of hydrochlorothiazide, we measured blood pressure, 24-hour urine sample collection, assessment of carotid-femoral pulse wave velocity (cf-PWV, Complior), central hemodynamic parameters (SphygmoCor), and post-occlusive reactive hyperemia (PORH). The participants were divided according to the tertile of 24-hour urinary Na/K ratio. Each group contained 24 patients. Systolic blood pressure was higher in T2 (133 ± 9 vs 140 ± 9 mmHg, P = .029). C-reactive protein (CRP) presented higher values in T3 as compared to T1 [0.20(0.10-0.34) vs 1.19 (0.96-1.42) mg/dL, P < .001]. Higher values in T3 were also observed for aortic systolic pressure (aoSP) [119(114-130) vs 135(125-147) mmHg, P = .002] and cf-PWV (9.2 ± 1.6 vs 11.1 ± 1.5 m/s, P < .001). The urinary Na/K ratio presented significant correlations with proteinuria (r = .27, P = .023), CRP (r = .77, P < .001), cf-PWV (r = .41, P < .001), and post-occlusive reactive hyperemia on cutaneous vascular conductance (PORH CVC) (r = -.23, P = .047). By multivariate linear regression, it was detected an independent and significant association of cf-PWV with urinary Na/K ratio (R2  = 0.17, P < .001) and PORH CVC with CRP (R2  = 0.30, P = .010). Our data indicated that increased urinary Na/K ratio in non-diabetic hypertensive patients was associated with higher degree of inflammation, raised peripheral and central pressure levels, and changes suggestive of endothelial dysfunction and arterial stiffness.

Molecular prognosticators in clinically and pathologically distinct cohorts of head and neck squamous cell carcinoma-A meta-analysis approach.

Head and neck squamous cell carcinomas (HNSCC) includes multiple subsites that exhibit differential treatment outcome, which is in turn reflective of tumor stage/histopathology and molecular profile. This study hypothesized that the molecular profile is an accurate prognostic adjunct in patients triaged based on clinico-pathological characteristics. Towards this effect, publically available micro-array datasets (n = 8), were downloaded, classified based on HPV association (n = 83) and site (tongue n = 88; laryngopharynx n = 53; oropharynx n = 51) and re-analyzed (Genespring; v13.1). The significant genes were validated in respective cohorts in The Cancer Genome Atlas (TCGA) for correlation with clinico-pathological parameters/survival. The gene entities (n = 3258) identified from HPV based analysis, when validated in TCGA identified the subset specifically altered in HPV+ HNSCC (n = 63), with three genes showing survival impact (RPP25, NUDCD2, NOVA1). Site-specific meta-analysis identified respective differentials (tongue: 3508, laryngopharynx: 4893, oropharynx: 2386); validation in TCGA revealed markers with high incidence (altered in >10% of patients) in tongue (n = 331), laryngopharynx (n = 701) and oropharynx (n = 404). Assessment of these genes in clinical sub-cohorts of TCGA indicated that early stage tongue (MTFR1, C8ORF33, OTUD6B) and laryngeal cancers (TWISTNB, KLHL13 and UBE2Q1) were defined by distinct prognosticators. Similarly, correlation with perineural/angiolymophatic invasion, identified discrete marker panels with survival impact (tongue: NUDCD1, PRKC1; laryngopharynx: SLC4A1AP, PIK3CA, AP2M1). Alterations in ANO1, NUDCD1, PIK3CA defined survival in tongue cancer patients with nodal metastasis (node+ECS-), while EPS8 is a significant differential in node+ECS- laryngopharyngeal cancers. In oropharynx, wherein HPV is a major etiological factor, distinct prognosticators were identified in HPV+ (ECHDC2, HERC5, GGT6) and HPV- (GRB10, EMILIN1, FNDC1). Meta-analysis in combination with TCGA validation carried out in this study emphasized on the molecular heterogeneity inherent within HNSCC; the feasibility of leveraging this information for improving prognostic efficacy is also established. Subject to large scale clinical validation, the marker panel identified in this study can prove to be valuable prognostic adjuncts.