Mismatch novelty exploration training shifts VPAC1 receptor-mediated modulation of hippocampal synaptic plasticity by endogenous VIP in male rats.

Novelty influences hippocampal-dependent memory through metaplasticity. Mismatch novelty detection activates the human hippocampal CA1 area and enhances rat hippocampal-dependent learning and exploration. Remarkably, mismatch novelty training (NT) also enhances rodent hippocampal synaptic plasticity while inhibition of VIP interneurons promotes rodent exploration. Since VIP, acting on VPAC1 receptors (Rs), restrains hippocampal LTP and depotentiation by modulating disinhibition, we now investigated the impact of NT on VPAC1 modulation of hippocampal synaptic plasticity in male Wistar rats. NT enhanced both CA1 hippocampal LTP and depotentiation unlike exploring an empty holeboard (HT) or a fixed configuration of objects (FT). Blocking VIP VPAC1Rs with PG 97269 (100 nM) enhanced both LTP and depotentiation in naïve animals, but this effect was less effective in NT rats. Altered endogenous VIP modulation of LTP was absent in animals exposed to the empty environment (HT). HT and FT animals showed mildly enhanced synaptic VPAC1R levels, but neither VIP nor VPAC1R levels were altered in NT animals. Conversely, NT enhanced the GluA1/GluA2 AMPAR ratio and gephyrin synaptic content but not PSD-95 excitatory synaptic marker. In conclusion, NT influences hippocampal synaptic plasticity by reshaping brain circuits modulating disinhibition and its control by VIP-expressing hippocampal interneurons while upregulation of VIP VPAC1Rs is associated with the maintenance of VIP control of LTP in FT and HT animals. This suggests VIP receptor ligands may be relevant to co-adjuvate cognitive recovery therapies in aging or epilepsy, where LTP/LTD imbalance occurs.

Pushing Backwards: Evaluating Effectiveness of Conservative Treatment of Intestinal Intussusception.

OBJECTIVE: Intestinal intussusception (II) is a common cause for acute abdomen in children, occurring in 0.33 to 0.71 per 1000 children per year. Early diagnosis and treatment are fundamental for prevention of irreversible intestinal damage. The first line of treatment is conservative, with saline reduction enema or air reduction enema. Our goal is to evaluate results with conservative treatment of II in children. METHODS: A retrospective single-center review of all patients with diagnosis of II from January 2014 to December 2019 was performed. Demographics, clinical data, treatment option, and results were assessed. RESULTS: Thirty-eight cases were identified. The mean age was 26 months, and 68% were males. Most presented with abdominal pain (95%) and vomiting (66%), after an average of 30 hours. Rectal bleeding was present in 32% of patients. Abdominal ultrasound was performed in all patients for diagnosis. Conservative treatment was first option in 95% of patients, with a global effectiveness of 83% after 1 attempt. Saline reduction enema was more effective than air reduction enema (88% vs 70%), and patients with successful reduction were younger (24 vs 33 months), but neither reached statistical significance. Two patients had a subsequent II episode within 1 week after hospital discharge. Neither age, sex, symptoms and respective duration, rotavirus inoculation, intussuscepted bowel length, nor technique used was predictive of treatment failure or II relapse. CONCLUSIONS: Conservative treatment in II is a safe and effective option, preventing invasive surgical procedures. Effectiveness of such treatments may be as high as 88% after 1 attempt, with rapid diet reintroduction. Same-day discharge after oral feeding toleration is safe.

Polyoxometalates Impact as Anticancer Agents.

Polyoxometalates (POMs) are oxoanions of transition metal ions, such as V, Mo, W, Nb, and Pd, forming a variety of structures with a wide range of applications. Herein, we analyzed recent studies on the effects of polyoxometalates as anticancer agents, particularly their effects on the cell cycle. To this end, a literature search was carried out between March and June 2022, using the keywords "polyoxometalates" and "cell cycle". The effects of POMs on selected cell lines can be diverse, such as their effects in the cell cycle, protein expression, mitochondrial effects, reactive oxygen species (ROS) production, cell death and cell viability. The present study focused on cell viability and cell cycle arrest. Cell viability was analyzed by dividing the POMs into sections according to the constituent compound, namely polyoxovanadates (POVs), polyoxomolybdates (POMos), polyoxopaladates (POPds) and polyoxotungstates (POTs). When comparing and sorting the IC50 values in ascending order, we obtained first POVs, then POTs, POPds and, finally, POMos. When comparing clinically approved drugs and POMs, better results of POMs in relation to drugs were observed in many cases, since the dose required to have an inhibitory concentration of 50% is 2 to 200 times less, depending on the POMs, highlighting that these compounds could become in the future an alternative to existing drugs in cancer therapy.

Reuse of lime sludge from immediate one-step lime precipitation process as a coagulant (aid) in slaughterhouse wastewater treatment.

The circularity of wastewater treatment subproducts is on the worldwide agenda. In this way, this work aims to evaluate alternatives for the reuse of sludge from slaughterhouse wastewater treatment. Wetted sludges produced in the immediate one-step lime precipitation process were applied directly or first calcined, as a coagulant or coagulant aid, in the absence or presence of Ca(OH)2, to slaughterhouse wastewaters with different characteristics. For the best sludge reuse, successive reuses of the sludge were carried out and the characteristics of treated slaughterhouse wastewater were evaluated after each reuse. Results showed a great similarity between slaughterhouse and treated slaughterhouse wastewaters using wetted and calcined sludges as a coagulant for highly contaminated slaughterhouse wastewater. In addition, a great similarity was also observed between the calcined and the wetted sludges, both as a coagulant aid, for all the slaughterhouse wastewaters tested. However, the latter consumed more hydrated lime, more volume of sludge sedimented, and higher concentrations phosphorus and organic matter in the treated wastewater. Calcined sludge as a coagulant aid guaranteed the best slaughterhouse wastewater quality for almost of the tested paramenters (≥94% for absorbances at 254 nm and 410 nm, E. coli, turbidity, and phosphorus, chemical oxygen demand between 3 and 91%, and total Kjeldahl nitrogen between 3 and 62%) independently of the wastewater characteristics. Calcined sludge as a coagulant aid can be three times reused for the tested parameters and slaughterhouse wastewater characteristics without significantly decreasing the quality. The successive sludge reused saves the hydrated lime dose applied (up to 28.4%) and the sedimented sludge volume (up to 24.7%), and can be a solution to stabilize sludge due to the pH increase (sludge pH = 12).

Skin temperature response to thermal stimulus in patients with hyperhidrosis: A comparative study.

Primary hyperhidrosis (HH), the excessive sweating exceeding physiological demand, has been associated to a complex dysfunction of the autonomic nervous system which may explain the disfunction in sweating but may also cause unrevealed alterations in skin blood flow regulation. In fact, HH patients present a sympathetic over-function with less reflex bradycardia in response to the Valsalva maneuver and higher sympathetic skin responses. We aimed to identify response patterns to room thermal stimulus in HH patients compared to a control group in order to investigate putative differences in blood flow assuming that skin temperature in glabrous (non-hairy) areas reflect the sympathetic tone in arteriovenous anastomoses (AVAs). Infrared thermography images were obtained from a cohort of patients diagnosed with HH, followed at a hospital pediatric surgical department and to a sex- and age-matched control group of patients admitted for other surgical procedures. With the participants in Fowler's position, a set of 3 images were captured simultaneously and 44 regions of interest were analyzed, distributed on the palms of the hands, soles of the feet, axilla, and inner canthus. After an acclimatization period at 20 °C, the room temperature was increased to 24, 28 and 32 °C to obtain similar sets of thermograms. A total of 37 patients with HH and 16 participants in the control group were included in the study. At baseline (20 °C), body core temperature (measured in the inner canthus) was significantly higher in the HH patients compared to the controls (p = 0.019 and p = 0.003 in right and left inner canthi, respectively), without any significant differences in the other thermograms. When room temperature was increased, differences in core temperature disappeared, while differences appeared in axilla and palms of the hands with HH patients presenting significantly lower temperature at the three thermal stimulus stages. Patients with HH presented a lower thermoregulatory response when submitted to room temperature increase, which may reflect a vasomotor sympathetic over-function in AVAs.

Pathogenic Vibrio species isolated from estuarine environments (Ceará, Brazil) - antimicrobial resistance and virulence potential profiles.

Detection of virulent strains associated with aquatic environment is a current concern for the management and control of human and animal health. Thus, Vibrio diversity was investigated in four estuaries from state of Ceará (Pacoti, Choró, Pirangi and Jaguaribe) followed by antimicrobial susceptibility to different antimicrobials used in aquaculture and detection of main virulence factors to human health. Isolation and identification were performed on TCBS agar (selective medium) and dichotomous key based on biochemical characteristics, respectively. Nineteen strains of genus Vibrio were catalogued. Vibrio parahaemolyticus (Choró River) and V. alginolyticus (Pacoti River) were the most abundant species in the four estuaries. All strains were submitted to disk diffusion technique (15 antimicrobials were tested). Resistance was found to: penicillin (82%), ampicillin (54%), cephalotin (7%), aztreonan (1%), gentamicin, cefotaxime and ceftriaxone (0.5%). Five pathogenic strains were chosen to verification of virulence factors. Four estuaries showed a high abundance of species. High number of tested positive strains for virulence is concerning, since some of those strains are associated to human diseases, while others are known pathogens of aquatic organisms.

A case of equine multicentric lymphoma: Clinical, microscopical, and molecular findings.

Background: Although relatively uncommon, lymphoma is the most prevalent haematopoietic neoplasia in horses, and multicentric lymphoma remains the most common presentation of the disease. The pathogenesis of equine lymphoma is still poorly understood and the diagnosis is usually confirmed at an advanced stage of the disease, compromising the prognosis. This study investigated the clinical, pathological, and molecular features of a case of equine multicentric lymphoma. Case Description: An apparently healthy 5-year-old crossbreed mare hospitalized at the Centre of Animal Reproduction of Vairão, Portugal, suddenly presented clinical signs of supraorbital oedema and mandibular lymph node enlargement, developing fever, facial oedema, and generalized lymphadenopathy. The mare ended up dying twenty-four days after the first clinical signs due to multisystem organ failure. Haematological and biochemical analyses, necropsy, and microscopic and molecular evaluation of affected tissues were performed. At necropsy, the main findings were multiple multinodular lesions, distributed along the serous surface of oropharynx, trachea, pericardium, gastrointestinal tract, and mesentery. Microscopically, these consisted of solid proliferations of neoplastic round cells that exhibited immunopositivity for CD3 (T cells). Based on these findings, a medium-grade multicentric T-cell lymphoma was diagnosed. Conclusion: There is still very little research regarding the molecular characterization of lymphoma in horses. As an entity itself is quite heterogeneous, it is important to describe the interspecies particularities to understand its development and behaviour.

Fenton-like application to pretreated cheese whey wastewater.

Cheese whey wastewater has been treated by the Fenton-like oxidation system after being pre-processed through a coagulation - flocculation stage with FeCl3 or alternatively, through a sedimentation step with Ca(OH)2 plus aerobic digestion. In the first case, Fenton-like oxidation is capable of reducing the initial COD (chemical oxygen demand) to 80% of the initial value, 20% of COD shows recalcitrance to chemical oxidation regardless of the operating conditions used. In the second case, the oxidation system is capable of removing almost the total COD present in the pretreated effluent. Given the lower values of initial COD, complete COD conversion is achieved at short reaction times within minutes depending on the initial reagent concentration. Removal of Fe(III) from the oxidation treatment can be achieved by Ca(OH)2 addition. Sedimentation pH significantly affects the observed settling rate. Hence, neutral conditions lead to better results than slightly acidic pHs.

Growth and development of tomato plants Lycopersicon Esculentum Mill. under different saline conditions by fertirrigation with pretreated cheese whey wastewater.

Pretreated cheese whey wastewater (CWW) has been used at different salinity levels: 1.75, 2.22, 3.22, 5.02 and 10.02 dS m(-1) and compared with fresh water (1.44 dS m(-1)). Two cultivars (cv.) of the tomato plant Lycopersicon Esculentum Mill. (Roma and Rio Grande) were exposed to saline conditions for 72 days. Salinity level (treatment) had no significant effects on the fresh weight and dry matter of the leaves, stems and roots. Similar results were found when specific leaf area, leaflet area, ramifications number of 1st order/plant, stem diameter and length, nodes number/stem and primary root length were considered. Conversely, the salinity level significantly influenced the Soil Plant Analysis Development (SPAD) index and the distance between nodes in the plant stem. In the first case, an increase of 21% was obtained in the salinity levels of 5.02 and 10.02 dS m(-1) for cv. Rio Grande, compared with the control run. The results showed that the pretreated CWW can be a source of nutrients for tomato plants, with reduced effects on growth and development.

Exploring Environmental Settings to Improve the Printability of Paroxetine-Loaded Filaments by Fused Deposition Modelling.

The successful integration of hot-melt extrusion (HME) and fused deposition modelling (FDM) depends on a better understanding of the impact of environmental conditions on the printability of formulations, since they significantly affect the properties of the raw materials, whose control is crucial to enable three-dimensional printing (3DP). Hence, the objective of this work was to investigate the correlation between the environmental settings and the properties of paroxetine (PRX)-loaded filaments, previously produced by HME, which affect printability by FDM. The influence of different drying methods of the physical mixtures (PMs) and HME-filaments (FILs) on the quality and printability of these products was also assessed. The printability of FILs was evaluated in terms of the water content, and the mechanical and thermal properties of the products. Stability studies and physicochemical, thermal, and in vitro dissolution tests were carried out on the 3D-printed tablets. Stability studies demonstrated the high ductility of the PRX loaded FILs, especially under high humidity conditions. Under low humidity storage conditions (11% RH), the FILs became stiffer and were successfully used to feed the FDM printer. Water removal was slow when carried out passively in a controlled atmosphere (desiccator) or accelerated by using active drying methods (heat or microwave). Pre-drying of the PRX/excipients and/or PMs did not show any positive effect on the printability of the FIL. On the contrary, dry heat and, preferably, microwave mediated drying processes were shown to reduce the holding time required for successful FDM printing, enabling on-demand production at the point of care.

Landfill leachate treatment by immediate one-step lime precipitation, carbonation, and phytoremediation fine-tuning.

The high pollutant load of sanitary landfill leachates poses a huge challenge in the search for efficient and environment friendly solutions for their treatment. The objective of this work was to study an integrated solution of environmentally friendly technologies - immediate one-step lime precipitation (IOSLP), carbonation (CB), and phytoremediation (Phyt) - to treat a sanitary landfill leachate. In the leachate sample treatment by IOSLP, the influence of CaO concentration (18.2-33.3 gCaO L-1) and stirring time (2-60 min) on the sludge sedimentability and pollutant removal was studied. Organic load and ammonia nitrogen (AN) removal increases with CaO added, as well as sludge volume. Stirring time has a small influence on organic load and AN removal, presenting a minimum for sludge volume. Thus, the best operational conditions were chosen as 27.6 gCaO L-1, and 40-min stirring time, with 64% chemical oxygen demand (COD) removal. Sludge humidity was 2.1%, making dewatering needless. IOSLP supernatant was submitted to CB by atmospheric CO2, and 100% removals in AN and hardness were attained. Effluents from IOSLP and IOSLP + CB were utilized in Phyt tests, with Vetiver (Chrysopogon zizanioides (L.) Roberty). The best COD removal (37%) during Phyt was attained for the samples treated by IOSLP + CB.

Quality of life after otoplasty for prominent ears in children.

AIM: Prominent ears are a common congenital malformation and are associated with low self-esteem, social isolation and diminished school performance. Our goal was to evaluate the influence of otoplasty on children's quality of life (QoL). MATERIAL AND METHODS: Patients submitted to otoplasty from 2016 to 2018 were summoned for a reevaluation. Seventy patients and respective caregivers agreed to participate. Surgical, demographic and clinical data were reviewed from electronic registries. TWO SETS OF INQUIRIES WERE PERFORMED: Pediatric Quality of Life Inventory 4.0 (for parent and child) and an adaptation of the Glasgow Children Benefit Inventory (GCBI-b). Fifteen patients were excluded for incomplete inquiries. RESULTS: Fifty-five patients were included, 70.9% were males. Median age at surgery was 7.7 ±â€¯3.3 years. Aesthetic dissatisfaction was the main previous negative experience. Median self-report quality of life was 85.6% and parent-report was 86.9%. Median GCBI-b was +20.5, indicating an improvement in patients' QoL. Bullying and high parental expectations for life change post-surgery were predictive of higher GCBI-b scores (p < 0.05). Ninety-six percent of parents would recommend surgery to other children. CONCLUSIONS: Otoplasty is a valid treatment option for prominent ears in children,improving not only aesthetics but also health-related QoL.

Case report: Long term follow-up of a large unilateral epididymal cyst in a stallion used for teaching: Is this condition associated with infertility?

A 30-year-old Lusitano stallion presented with an enlarged right epididymis. The ultrasound scan revealed a cyst-like formation and the histopathological examination was compatible with epididymal cyst located at the body/tail transition, epididymal spermatocele and sperm granuloma and epididymitis. However, these conditions did not seem to affect the animal's reproductive performance, nor did the semen parameters analyzed over the 8 years after the diagnosis show significant changes. Nevertheless, since the ejaculate contains mostly sperm cells from the tail of the epididymis, where fertile spermatozoa are stored until ejaculated, a deep knowledge of the different conditions that can affect this organ is of the utmost importance.

Structural study and antimicrobial and wound healing effects of lectin from Solieria filiformis (Kützing) P.W.Gabrielson.

The SfL-1 isoform from the marine red algae Solieria filiformis was produced in recombinant form (rSfL-1) and showed hemagglutinating activity and inhibition similar to native SfL. The analysis of circular dichroism revealed the predominance of ß-strands structures with spectra of ßI-proteins for both lectins, which had Melting Temperature (Tm) between 41 °C and 53 °C. The three-dimensional structure of the rSfL-1 was determined by X-ray crystallography, revealing that it is composed of two ß-barrel domains formed by five antiparallel ß chains linked by a short peptide between the ß-barrels. SfL and rSfL-1 were able to agglutinate strains of Escherichia coli and Staphylococcus aureus and did not show antibacterial activity. However, SfL induced a reduction in E. coli biomass at concentrations from 250 to 125 µg mL-1, whereas rSfL-1 induced reduction in all concentrations tested. Additionally, rSfL-1 at concentrations from 250 to 62.5 µg mL-1, showed a statistically significant reduction in the number of colony-forming units, which was not noticed for SfL. Wound healing assay showed that the treatments with SfL and rSfL-1 act in reducing the inflammatory response and in the activation and proliferation of fibroblasts by a larger and fast deposition of collagen.

Cheese whey management: a review.

Cheese whey is simultaneously an effluent with nutritional value and a strong organic and saline content. Cheese whey management has been focused in the development of biological treatments without valorization; biological treatments with valorization; physicochemical treatments and direct land application. In the first case, aerobic digestion is reported. In the second case, six main processes are described in the literature: anaerobic digestion, lactose hydrolysis, fermentation to ethanol, hydrogen or lactic acid and direct production of electricity through microbial fuel cells. Thermal and isoelectric precipitation, thermocalcic precipitation, coagulation/flocculation, acid precipitation, electrochemical and membrane technologies have been considered as possible and attractive physicochemical processes to valorize or treat cheese whey. The direct land application is a common and longstanding practice, although some precautions are required. In this review, these different solutions are analyzed. The paper describes the main reactors used, the influence of the main operating variables, the microorganisms or reagents employed and the characterizations of the final effluent principally in terms of chemical oxygen demand. In addition, the experimental conditions and the main results reported in the literature are compiled. Finally, the comparison between the different treatment alternatives and the presentation of potential treatment lines are postulated.

Performance and paroxetine stability in tablets manufactured by fused deposition modelling-based 3D printing.

OBJECTIVES: The objective of this study was to develop a method for the preparation and characterization of paroxetine (PRX) tablets, obtained by coupling hot-melt extrusion and fused deposition modelling (FDM)-based three-dimensional printing (3DP) technology. The impact of the printing process parameters on the drug stability and on the tablets performance was assessed. METHODS: Tablets were obtained by FDM of hot-melt extruded PRX-loaded filaments. Physicochemical, thermal, spectroscopic, diffractometric analysis and in-vitro dissolution tests of the intermediate products and the finished dosage forms were performed. KEY FINDINGS: The characterization of printed tablets evidenced mass and dimensions uniformity, and consistency of drug content and dissolution profile. The formation of amorphous solid dispersions and interaction of formulation components throughout the manufacturing process were demonstrated. Layer thickness, printing temperature, printing and travelling speeds, and infill were the most impacting process parameters on both the physicochemical properties and the in-vitro performance of the 3D-printed tablets. CONCLUSIONS: PRX tablets, meeting compendial limits, were manufactured by 3DP, envisaging their clinical use as individually designed dosage forms. The assessment of the impact of processing parameters on the printed tablets provided insights, which will ultimately allow streamlining of the 3D process set-up for quicker and easier production of patient-centric medicines.

Immunohistochemical Expression of Platelet-Derived Growth Factor Receptor ß (PDGFR-ß) in Canine Cutaneous Peripheral Nerve Sheath Tumors: A Preliminary Study.

As in humans, the prevalence of tumors in companion animals is increasing dramatically and there is a strong need for research on new pharmacological agents particularly for the treatment of those tumors that are resistant to conventional chemotherapy agents such as soft tissue sarcomas (STS). Because malignant (MPNST) and benign peripheral nerve sheath tumors (BPNST) are relatively common STS in dogs, the aim of this retrospective study was to evaluate the immunohistochemical (IHC) expression of PDGFR-ß, contributing to its characterization as a potential target for their treatment. A total of 19 samples were included, 9 histologically classified as benign and the other 10 as malignant. The results showed diffuse immunoexpression in the cytoplasm of neoplastic cells. Six (66.7%) BPNST expressed the receptor in less than 25% of neoplastic cells and only three (33.3%) exhibited labelling in more than 25% of neoplastic cells. In contrast, all MPNST expressed PDGFR-ß, and in 8 (80%) of these samples, the receptor was expressed in more than 25% of neoplastic cells, and only 2 (20%) cases expressed the receptor in less than 25% of neoplastic cells. PDGFR-ß expression was significantly higher in MPNST and larger tumors, suggesting that drugs able to inhibit the activity of this tyrosine kinase receptor, such as toceranib, may be considered in the approach of unresectable tumors and/or in the context of adjuvant or neoadjuvant therapies.