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.

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.

Quality of life after otoplasty for prominent ears in children

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 methodsPatients 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 performedPediatric 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.ResultsFifty-five patients were included, 70.9% were males. Median age at surgery was 7.7 ± 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.ConclusionsOtoplasty is a valid treatment option for prominent ears in children,improving not only aesthetics but also health-related QoL. (AU)

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).

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.

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.

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.

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.

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.

Mediastinal Teratoma In Children - Case Report.

Mediastinal teratomas presenting in the pediatric age are extremely rare. We report three cases of mediastinal teratomas in children aged 15 months to 9 years. Patients were submitted to complete tumor resection, with an uneventful postoperative course and follow-up. Our report emphasizes the importance of a detailed patient examination and careful interpretation of routinely performed image studies.

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.

Early results of a distance learning paediatric surgery programme in Mozambique.

Introduction: A pre-graduate training programme in paediatric surgery was applied to students in four medical schools of Mozambique. In this paper, we evaluate the early results of the programme. Materials and Methods: A pre-graduate training programme was developed and applied in two stages, theoretical education available at an online platform and a face-to-face session. To evaluate the programme, a diagnostic test was applied to all participants before the face-to-face session and, the same test, was applied again at the end of the session. Results: A total of 236 students participated in the programme. Forty-four per cent had a negative score on the diagnostic test. When the test was repeated, 91.9% had a positive score, and the difference between the scores in both tests reached statistical significance (P < 0.05). The participants who completed the first phase of the programme presented a higher median score in both tests (P < 0.05). Conclusions: : The diagnostic tests allowed us to verify there was an increase in knowledge before and after the face-to-face session. There was also a significant difference between those participants who completed the online phase of the programme and those who did only the face-to-face session, which allows us to conclude that the online teaching programme was effective.

Pharyngeal Airspace Alterations after Using the Mandibular Advancement Device in the Treatment of Obstructive Sleep Apnea Syndrome.

BACKGROUND: Mandibular Advancement Devices (MADs), inserted in non-surgical treatments for obstructive sleep apnea and hypopnea syndrome (OSAHS), are used intra-orally during the sleep period, with the aim of promoting mandibular protrusion. The aim of the study is to analyze the changes in the upper airway after the use of an MAD in the treatment of OSAHS. METHODS: 60 patients diagnosed with OSAHS, as established by the Sleep Medicine Service, underwent treatment with the Silensor SL device at the Stomatology Service of the University Hospital Center of Coimbra, from January 2018 to January 2019. All patients completed two polysomnographies and two lateral teleradiographies: one before starting treatment (T0) and one after 1 year of treatment (T1). In the lateral teleradiography performed after one year of treatment, the patient had the MAD placed intra-orally. The linear measurements of the airspace proposed by the Arnett/Gunson FAB Surgery cephalometric analysis were measured at four craniometric points: A, MCI, B, Pog. RESULTS: The results demonstrate an anteroposterior airway enlargement in two of the four points studied with the MAD placed intra-orally (B and Pog point). The greatest average increase is observed at point Pog (3 mm), followed by B (1 mm), and finally, point A (0.6 mm). CONCLUSIONS: This study proved that there is an improvement in anteroposterior measurements at various points in the upper airways after treatment with MAD.

PLEURAL METASTASIS OF A PEDIATRIC OSTEOSARCOMA.

INTRODUCTION: Osteosarcoma is the most common primary bone tumor in children and young adults. Although osteosarcoma is a tumor with a great metastatic potential, mainly to the lung; pleural metastasis in patients with osteosarcoma are rarely reported. We present a case of 16 years-old male with a pleural metastasis of a tibial osteosarcoma diagnosed 4years earlier. He was submitted to a left thoracotomy and intra-operatively a pleural mass and a left upper lobe lesion was identified. Video-assisted resection of the extra-pulmonary mass and a wedge resection of the left upper lobe lesion was performed. The surgery was uneventful. The patient is clinically well, asymptomatic, maintains active surveillance.

Compensatory sweating after thoracoscopic sympathectomy for primary focal hyperhidrosis in children: Are there patient-related risk factors?

INTRODUCTION: Compensatory sweating (CS) is a common complication after thoracoscopic sympathectomy (TS) and is mainly associated with surgical technique. Our aim was to identify potential risk-factors for CS following TS for primary focal hyperhidrosis in children. METHODS: A retrospective, single-center review of all bilateral TS was performed between 2017 and 2019. Hyperhidrosis disease severity scale was used for pre-operative severity assessment. Post-operative evaluations were performed after three and six months. RESULTS: More than the 36-month period, 41 patients were submitted to T2-T4 TS, and 25 were females (60.9%). Median age at surgery was 15.5 years. CS was identified at the 3rd month in 17 (41%) children with most in the dorsolumbar region (56%). By the 6th month, there was a significant reduction in CS (41 to 32%, p = 0.02). The probability of resolution of CS by 6 months is about 50% in both the dorsolumbar and abdominal regions. Neither age, gender, body mass index, family history, or concomitant illnesses seemed to influence CS (p > 0.05). Axillary hyperhidrosis appears to be associated with the development of dorsolumbar CS (p = 0.037). CONCLUSION: Thoracoscopic sympathectomy for PFH is a safe and effective procedure, but compensatory sweating can be a common and debilitating side effect. Age, gender, and body mass index do not appear to influence CS. Axillary hyperhidrosis may be related to the development of dorsolumbar CS. LEVEL OF EVIDENCE: III.

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.

Pediatric Burns With Cyanoacrylate Glue: An Inconspicuous Danger.

Burns are a common cause of pediatric injury and represent significant morbidity and mortality in this age group. In children, most burns are thermal, resulting from exposure to a hot surface, liquid, or fire. Cyanoacrylate is a liquid compound commonly found in households, mainly in "superglue" and nail glue. This compound solidifies through an exothermic reaction that is magnified when in contact with certain fibers that act as catalysts, such as cotton. In these circumstances, intense heat is produced in the contact area, potentially causing severe thermal burns. Despite its widespread availability, there is a paucity of safety information about cyanoacrylate and its role as a cause for burns. In the literature, only 18 cases of cyanoacrylate burns are reported in children. We present two cases of pediatric burns with cyanoacrylate and a review of the literature.