Assessment of the chemical composition of buriti (Mauritia flexuosa Liliopsida) and cassava (Manihot esculenta Crantz) residues and their possible application in the bioproduction of coconut aroma (6 pentyl-α-pyrone).

This work aimed to define strategies to increase the bioproduction of 6 pentyl-α-pyrone (bioaroma). As first strategy, fermentations were carried out in the solid state, with agro-industrial residues: Mauritia flexuosa Liliopsida. and Manihot esculenta Crantz in isolation, conducting them with different nutrient solutions having Trichoderma harzianum as a fermenting fungus. Physicochemical characterizations, centesimal composition, lignocellulosic and mineral content and antimicrobial activity were required. Fermentations were conducted under different humidification conditions (water, nutrient solution without additives and nutrient solutions with glucose or sucrose) for 9 days. Bioaroma was quantified by gas chromatography, assisted by solid-phase microextraction. The results showed the low production of this compound in fermentations conducted with sweet cassava (around 6 ppm (w/w)). The low bioproduction with sweet cassava residues can probably be related to its starch-rich composition, homogeneous substrate, and low concentration of nutrients. Already using buriti, the absence of aroma production was detected. Probably the presence of silicon and high lignin content in buriti minimized the fungal activity, making it difficult to obtain the aroma of interest. Given the characteristics presented by the waste, a new strategy was chosen: mixing waste in a 1:1 ratio. This fermentation resulted in the production of 156.24 ppm (w/w) of aroma using the nutrient solution added with glucose. This combination, therefore, promoted more favorable environment for the process, possibly due to the presence of fermentable sugars from sweet cassava and fatty acids from the buriti peel, thus proving the possibility of an increase of around 2500% in the bioproduction of coconut aroma.

Asleep versus awake GPi DBS surgery for Parkinson's disease: A systematic review and meta-analysis.

BACKGROUND: Patients with Parkinson's Disease (PD) who receive either asleep image-guided subthalamic nucleus deep brain stimulation (DBS) or the traditional awake technique have comparable motor outcomes. However, there are fewer studies regarding which technique should be chosen for globus pallidus internus (GPi) DBS. This systematic review and meta-analysis aims to compare the accuracy of lead placement and motor outcomes of asleep versus awake GPi DBS PD population. METHODS: We systematically searched PubMed, Embase, and Cochrane for studies comparing asleep vs. awake GPi DBS lead placement in patients with PD. Outcomes were spatial accuracy of lead placement, measured by radial error between intended and actual location, motor improvement measured using (UPDRS III), and postoperative stimulation parameters. Statistical analysis was performed with Review Manager 5.1.7. and OpenMeta [Analyst]. RESULTS: Three studies met inclusion criteria with a total of 247 patients. Asleep DBS was used to treat 192 (77.7 %) patients. Follow-up ranged from 6 to 48 months. Radial error was not statistically different between groups (MD -0.49 mm; 95 % CI -1.0 to 0.02; I2 = 86 %; p = 0.06), with a tendency for higher target accuracy with the asleep technique. There was no significant difference between groups in change on motor function, as measured by UPDRS III, from pre- to postoperative (MD 8.30 %; 95 % CI -4.78 to 21.37; I2 = 67 %, p = 0.2). There was a significant difference in postoperative stimulation voltage, with the asleep group requiring less voltage than the awake group (MD -0.27 V; 95 % CI -0.46 to - 0.08; I2 = 0 %; p = 0.006). CONCLUSION: Our meta-analysis indicates that asleep image-guided GPi DBS presents a statistical tendency suggesting superior target accuracy when compared with the awake standard technique. Differences in change in motor function were not statistically significant between groups.

Replacement of traditional vagus nerve stimulation with cardiac-based device and seizure reduction: A systematic review and meta-analysis.

INTRODUCTION: For patients with drug-resistant epilepsy (DRE) who are not suitable for surgical resection, neuromodulation with vagus nerve stimulation (VNS) is an established approach. However, there is limited evidence of seizure reduction when replacing traditional VNS (tVNS) device with a cardiac-based one (cbVNS). This meta-analysis compares the seizure reduction achieved by replacing tVNS with cbVNS in a population with DRE. METHODS: We systematically searched PubMed, Embase, and Cochrane Central following PRISMA guidelines. The main outcomes were number of patients experiencing a ≥ 50 % and ≥80 % reduction in seizures, as defined by the McHugh scale. Additionally, we assessed the number of patients achieving freedom from seizures. RESULTS: We included 178 patients with DRE from 7 studies who were initially treated with tVNS and subsequently had it replaced by cbVNS. The follow-up for cbVNS ranged from 6 to 37.5 months. There was a statistically significant reduction in seizure frequency with the replacement of tVNS by cbVNS, using a ≥ 50 % (OR 1.79; 95 % CI 1.07 to 2.97; I²=0 %; p = 0.03) and a ≥ 80 % (OR 2.06; 95 % CI 1.17 to 3.62; I²=0 %; p = 0.01) reduction threshold. Nineteen (13 %) participants achieved freedom from seizures after switching to cbVNS. There was no difference in the rate of freedom from seizures between groups (OR 1.85; 95 % CI 0.81 to 4.21; I²=0 %; p = 0.14). CONCLUSION: In patients with DRE undergoing battery replacement, cbVNS might be associated with seizure reduction (≥50 % and ≥80 % threshold) after switching from tVNS. Randomised controlled trials are necessary to validate these findings.

Acute food deprivation-induced relapse to heroin seeking after short and long punishment-imposed abstinence in male rats.

RATIONAL: Stress is a major trigger for drug relapse in humans and animal models, even after prolonged abstinence. However, animal models for stress-induced relapse were criticized for the lack of predictive and face validity. OBJECTIVES: Here we investigated the effect of acute food deprivation stress in a novel stress-induced relapse model using voluntary, punishment-imposed abstinence from heroin. We also performed a detailed characterization of the development of punishment-imposed abstinence. METHODS: Male rats were trained to self-administered heroin (0.1 mg/kg/infusion) for 2 weeks, using the seeking-taking chained schedule. Pressing the 'seeking' lever led to the insertion of the 'taking' lever and pressing the take lever resulted in heroin infusion. Following self-administration training, rats were exposed to 8 or 21 days of heroin-seeking punishment. During punishment, 30% of the completed seek links resulted in a mild escalating footshock instead of take lever presentation. Next, rats were tested for heroin seeking under extinction conditions after 24 h of food deprivation and sated conditions. RESULTS: Probabilistic punishment of seeking lever responses resulted in gradual suppression of heroin seeking and taking. Exposure to food-deprivation stress induced a robust relapse to heroin seeking after short and long punishment-imposed abstinence periods, without significant effects of time, i.e., no incubation of heroin seeking. Individual differences were observed in the development of punishment-induced abstinence and stress-induced relapse. CONCLUSIONS: These results suggest that stress is a reliable trigger to relapse even after a prolonged period of punishment-induced, voluntary abstinence.

Nanoparticles Obtained from Zein for Encapsulation of Mesalazine.

We encapsulated MSZ in zein nanoparticles (NP-ZN) using a desolvation method followed by drying in a mini spray dryer. These nanoparticles exhibited a size of 266.6 ± 52 nm, IPD of 0.14 ± 1.1 and zeta potential of -36.4 ± 1.5 mV, suggesting colloidal stability. Quantification using HPLC showed a drug-loaded of 43.8 µg/mg. SEM demonstrated a spherical morphology with a size variation from 220 to 400 nm. A FTIR analysis did not show drug spectra in the NPs in relation to the physical mixture, which suggests drug encapsulation without changing its chemical structure. A TGA analysis showed thermal stability up to 300 °C. In vitro release studies demonstrated gastroresistance and a sustained drug release at pH 7.4 (97.67 ± 0.32%) in 120 h. The kinetic model used for the release of MSZ from the NP-ZN in a pH 1.2 medium was the Fickian diffusion, in a pH 6.8 medium it was the Peppas-Sahlin model with the polymeric relaxation mechanism and in a pH 7.4 medium it was the Korsmeyer-Peppas model with the Fickian release mechanism, or "Case I". An in vitro cytotoxicity study in the CT26.WT cell line showed no basal cytotoxicity up to 500 µg/mL. The NP-ZN showed to be a promising vector for the sustained release of MSZ in the colon by oral route.

Cancer care for Ukrainian refugees: Strategic impact assessments in the early days of the conflict.

BACKGROUND: The invasion of Ukraine by Russia in February 2022 has resulted in destruction of healthcare infrastructure and triggered the largest wave of internally displaced populations and refugees since World War Two. Conflicts in transitioned countries such as Ukraine create new non-communicable disease (NCD) challenges, especially for cancer care for refugees and humanitarian assistance in host countries. In the early days, rapid attempts were made to model possible impacts. METHODS: By evaluating open source intelligence used in the first three months of the conflict through snowball search methods, we aimed to address: (i) burden of cancer in Ukrainian population, specifically considering translating to the refugees population, and its cancer care capacity; ii) baseline capacity/strengths of cancer systems in initial host countries. Moreover, using a baseline scenario based on crude cancer incidence in Ukraine, and considering data from UNHCR, we estimated how cancer cases would be distributed across host countries. Finally, a surveillance assessment instrument was created, intersecting health system's capacity and influx of internally displaced populations and refugees. FINDINGS AND CONCLUSIONS: The total new cancer patients per month in pre-conflict Ukraine was estimated as 13,106, of which < 1 % are paediatric cases. The estimated cancer cases in the refugee population (combining prevalent and incident), assuming 7.5 million refugees by July 2022 and a female:male ratio of 9:1, was 33,121 individuals (Poland: 19284; Hungary: 3484; Moldova: 2651; Slovakia: 2421; Romania: 5281). According to our assessments, Poland is the only neighbouring country classified as green/yellow for cancer capacity, i.e. sufficient ablility to absorb additional burden into national health system; Slovakia we graded as yellow, Hungary and Romania as yellow/red and Moldova as red.

Spatio-temporal dynamics of phytoplankton community in a well-mixed temperate estuary (Sado Estuary, Portugal).

Estuaries are highly productive ecosystems, which are strongly affected by several anthropogenic pressures. Phytoplankton is a key element for assessing the ecological quality status in these transitional waters. Moreover, understanding physico-chemical and biological drivers is crucial to disentangle their effect on the structure of phytoplankton community. The present work aims to study the effect of the main physico-chemical drivers on the phytoplankton community structure and dynamics in a temperate well-mixed estuary (Sado Estuary). Four sampling stations were analyzed monthly in three regions of the estuary, from 2018 to 2019. Surface water samples were collected to analyze the phytoplankton community and several concomitant physico-chemical parameters. Temperature, turbidity, salinity, and nutrients availability were the drivers that best explained the spatio-temporal patterns observed in the phytoplankton community. The upper estuary was characterized by higher phytoplankton cell abundances and biomass. Three phytoplankton groups stood out in the characterization of the estuarine assemblages: diatoms, cryptophytes, and dinoflagellates. Diatoms were the dominant group most of the year, being dominated by small cell species (single and chain-forming) upstream, and by larger chain-forming species downstream. Cryptophytes had a high contribution to the community in the inner regions of the estuary, while dinoflagellates contributed more for the community composition downstream, where high abundances of harmful algal species were sporadically found. Previous studies on the phytoplankton community dynamics in this estuary are limited to the 1990s. Thus, the present study provides insight into changes in the dominant phytoplankton groups of the Sado Estuary in the last 25 years, namely an increase in cryptophytes over diatoms in the inner estuarine regions, and an increase in dinoflagellates near the estuary mouth.

Spatiotemporal distribution of Schizaphis graminum (Rondani) and its natural enemy Coccinella septempunctata (Linnaeus) in graniferous sorghum crops.

At the global level, Sorghum bicolor (L.), is one of the most important crops, which ranks fifth among all cereals. It is cultivated in Africa, Asia, Oceania and the Americas, where it serves as a source of food and feed for humans and animals, respectively. However, production is constrained by several factors including pests and diseases. Among the pests that are known to attack Sorghum, Schizaphis graminum (Rondani), commonly called the green cereal aphid, is the most destructive pest of sorghum. S. graminum damage to sorghum is worsen by water deficit which favors its occurrence. Limited information on the spatial distribution of the pest and its natural enemies impedes the development of ecologically friendly management strategies. Therefore, the objective of this research was to determine the spatiotemporal distribution of S. graminum and its natural enemy Coccinella septempunctata (L.) during the vegetative and reproductive stage of the crop using geostatistical analysis. The spatiotemporal distribution of S. graminum was influenced by Sorghum development stage, surrounding landscape, and presence of its main predator C. septempunctata. Moreover, the abundance of C. septempunctata was influenced by the density of S. graminum. The findings from this study are required for developing sustainable pest management strategies against S. graminum.

Mucinous adenocarcinoma of the appendix invading the urinary bladder.

Appendiceal carcinoma is a rare disorder. Although imaging exams can suggest carcinoma of the appendix simulating as a primary bladder cancer a transurethral biopsy is essential for diagnosis. We reported a case of a 27-year-old man, presented with hypogastric pain associated with recurrent gross hematuria and dysuria but without any intestinal symptoms such as pain, obstruction or melena. MRI revealed an enlarged appendix contiguous with the bladder. An en-bloc resection was performed and revealed appendiceal mucinous adenocarcinoma. Carcinoma of the appendix is an important differential diagnosis to other lesions and allow a good chance of cure by en bloc resection.

Nutritional value and antioxidant compounds during the ripening and after domestic cooking of bananas and plantains.

Genotypes of bananas and plantains have been studied for biofortification purposes, mainly due to content of resistant starch (RS) and polyphenols. This study aims to identify banana and plantain genotypes with a high content of resistant starch, phenolic compounds and minerals, and to evaluate the impact of the ripening stage and domestic thermal processing to select superior genotypes with high levels of functional compounds. In this study, it was used bunches of bananas and plantain genotypes. The phenolic compounds profiles were determined by HPLC-DAD in pulps and peels. The resistant starch and the minerals (K, Na, Zn, Cu and Fe) were evaluated in pulps and peels of unripe fruit. The results of phenolic compounds were studied in three ripening stages, and after thermal processing (ripe stage) of two genotypes, which were most promising for biofortification studies. Resistant starch and minerals were analysed in the unripe fruits. The peel biomass showed the highest values of phenolic compounds and minerals. The total starch content in the pulp varied from 42.3% ('FC06-02') to 80.6% ('Pelipita'). Plantains and cooking bananas presented the highest contents of starch and resistant starch (stage 2 - green with yellow traces). The pulps of the dessert genotypes 'Khai' and 'Ouro da Mata', and cooking genotype 'Pacha Nadam' stood out due to their minerals high contents (P, K and Fe; Zn and Fe; Ca, Mg and Zn, respectively). The dessert bananas (e.g., 'Ney Poovan') and cooking bananas (e.g., 'Tiparot') had the highest concentrations of phenolic compounds, mainly in ripe fruit (stage 5 - yellow with green). In addition, the thermal processing of Musa spp. fruit led to increasing these secondary metabolites, mainly the cooking of fruit with peel by boiling, which should be preferred in domestic preparations.

Vitamin D restriction enhances periovarian adipose tissue inflammation in a model of menopause.

Background: Menopause and deficiency in vitamin D (VD) are two health problems usually associated with aging women.Objective: We aimed to study inflammation in visceral adipose tissue when bilateral ovariectomy is combined with dietary restriction in VD.Methods: We studied 60 female C57BL/6 mice 3 months of age. Half of the animals had bilateral ovariectomy (Ovx group, n = 30) and half a sham procedure (Control [C] group, n = 30), and half of each Ovx or C group were fed a standard diet containing VD or a diet restricted in VD (D-) for an additional 12 weeks. Therefore, four groups were formed (n = 15 each group): C, C(D-), Ovx, and Ovx(D-). After sacrifice, the periovarian adipose tissue (PAT) was investigated.Results: In PAT, we observed different levels of hypertrophied adipocytes, enhanced proinflammatory cytokines, activation of inflammatory markers, and components of the extracellular signal-regulated kinase. The most affected PAT was seen in the Ovx(D-) group, followed by the Ovx group, the C(D-) group, and the C group (the least altered).Conclusion: The results demonstrate that ovariectomy and dietary restriction of VD are inducers of adverse effects on mouse visceral adipose tissue. When combined, these insults might enhance PAT inflammation.

Prenatal exposure to betamethasone causes intergenerational impairment of epididymal development in the rat.

BACKGROUND: Studies on epididymal toxicology are scarce. Betamethasone (BM) is a glucocorticoid used in clinical practice for antenatal therapy. We previously reported changes to testicular morphology, altered sperm quality, and fertility in adult rats following intrauterine administration of BM. OBJECTIVES: Given that high levels of corticosteroids during gestation lead to fetal androgen depletion, and the essential role of testosterone during epididymal development, here we investigated epididymal morphology and physiology in the F1 and F2 male offspring of female rats treated with BM during gestation. MATERIALS AND METHODS: Pregnant rats were randomly divided into two experimental groups: control (saline vehicle, n = 11) and BM-treated group (0.1 mg/kg betamethasone 21-phosphate disodium, n = 13). Rats received an intramuscular injection of vehicle or BM on gestational days 12, 13, 18, and 19. This encompasses the beginning of the critical window of male rat reproductive tract development. A subset of three males from each litter (n = 5 litters/group) was used: One rat per litter was euthanized at puberty, one was euthanized at adulthood, while the others were mated with a non-treated female to obtain the F2 generation. The same protocol described for the F1 was applied for F2, except for the mating protocol. RESULTS: In both F1 and F2 generations, prenatal BM exposure resulted in delayed differentiation of the cauda epididymal epithelium, characterized by increased cribriform appearance on PND 45, and displayed weaker or non-detectable Cx43 immunostaining. Furthermore, in the F1 generation only, immunostaining of TP63, a transcription factor expressed in basal cells, appeared more intense with a greater number of TP63-positive cells observed in the cauda epididymis. In adults, the epithelial area was reduced in the F1 BM rats. The contractile activity of isolated epididymal ducts was comparable between groups. DISCUSSION AND CONCLUSION: Prenatal BM exposure leads to intergenerational impairment in the development and structure of the rat epididymis.

Identification and management of a subacute right ventricular perforation by an active-fixation permanent pacemaker lead in a dog.

A 5-year-old short-haired dachshund was referred with a history of repeated syncope associated with a third-degree atrioventricular block. A permanent transvenous pacemaker with an active-fixation lead was implanted. In the following 3 weeks, the syncopal episodes reappeared owing to a loss of ventricular capture. The pacemaker was reprogrammed to higher output, and effective pacing was re-established. Thoracic radiographs and echocardiography failed to identify any evidence of lead displacement. One month later, the patient presented a new episode of loss of capture. After fluoroscopy, cardiac perforation was suspected and subsequently confirmed by thoracotomy. An epicardial pacemaker lead was implanted without removing the perforating lead as there were no bleeding complications or damage to adjacent organs, and the length of time elapsed since implantation was assumed to have allowed for significant fibrotic adhesions to develop. Nineteen months after epicardial pacemaker implantation, endocardial lead dislodgement occurred. Simultaneously, the dog presented with gastrointestinal and respiratory abnormalities and severe thrombocytopenia. Once the dog was stabilized, the endocardial lead was percutaneously removed. One month later, loss of ventricular capture recurred. The owners declined any further treatment, and euthanasia was elected. Cardiac perforation after pacemaker implantation is an infrequent complication. In this case, the dog lived 22 months after subacute right ventricular perforation. Despite the poor prognosis associated with cardiac perforation by pacemaker leads, different approaches are possible to successfully manage this major complication. Extraction of the displaced lead remains controversial as, if the lead is not removed, late lead migration can occur.

Long-term outcomes of transmesenteric portal vein recanalization for the treatment of chronic portal vein thrombosis after pediatric liver transplantation.

Portal vein thrombosis (PVT) may occur at any time following liver transplantation. We describe our experience with portal vein recanalization in cases of thrombosis after liver transplantation. Twenty-eight children (5%) out of 566 liver transplant recipients underwent portal vein recanalization using a transmesenteric approach. All children received left hepatic segments, developed PVT, and had symptoms or signs of portal hypertension. Portal vein recanalization was performed via the transmesenteric route in all cases. Twenty-two (78.6%) patients underwent successful recanalization and stent placement. They received oral anticoagulants after the procedure, and clinical symptoms subsided. Symptoms recurred due to portal vein restenosis/thrombosis in seven patients. On an intention-to-treat basis, the success rate of the proposed treatment was 60.7%. Only 17 out of 28 children with posttransplant chronic PVT retained stent patency (primary + assisted) at the end of the study period. In cases of portal vein obstruction, the transmesenteric approach via minilaparotomy is technically feasible with good clinical and hemodynamic results. It is an alternative procedure to reestablish the portal flow to the liver graft that can be performed in selected cases and a therapeutic addition to other treatment strategies currently used to treat chronic PVT.

Identificación de nuevos genes candidatos para la retinopatía en diabéticos tipo 2. Estudio Valencia sobre Retinopatía Diabética (EVRD). Informe n.° 3 / Identification of new candidate genes for retinopathy in type 2 diabetics. Valencia Study on Diabetic Retinopathy (VSDR). Report number 3

OBJETIVO: Identificar genes implicados en los mecanismos patogénicos de la retinopatía diabética no proliferante, como estrés oxidativo, alteración de la matriz extracelular y/o apoptosis, para valorar el riesgo de desarrollo de la misma en una población de diabéticos tipo2 (DM2). MATERIAL Y MÉTODOS: Estudio de casos y controles en 81 participantes del Estudio Valencia sobre Retinopatía Diabética (EVRD), de ambos sexos y con edades comprendidas entre los 25 y 85 años, clasificados en: 1) grupo DM2 (n = 49), con RD (+RD; n = 14) y sin RD (−RD; n = 35), y 2)grupo control (GC; n=32). Se realizó entrevista personal, examen oftalmológico estandarizado y extracción de sangre que se procesó para analizar el ADN y determinar la expresión de: TP53, MMP9 y SLC23A2 en todos los participantes. El programa estadístico utilizado fue el SPSS v22.0. RESULTADOS: Los genes TP53 y MMP9 aumentaron su expresión en el grupo DM2 respecto al GC, aunque solo de manera significativa el gen MMP9 (TP53: 10,40 ± 1,20 vs. 8,23 ± 1,36, p = 0,084; MMP9: 1,45 ± 0,16 vs. 0,95 ± 0,16, p = 0,036) y el gen SLC23A2 disminuyó significativamente sus niveles en DM2 vs. GC (5,58 ± 0,64 vs. 11,66 ± 1,90, p = 0,026). Al subdividir el grupo DM2 según presencia de retinopatía, la expresión de los genes TP53, MMP9 y SLC23A2 mostró diferencias significativas entre los grupos DM2−RD, DM2+RD y GC (TP53: 9,95 ± 1,47 vs. 11,52 ± 2,05 vs. 8,23 ± 1,36, p = 0,038; MMP9: 1,47 ± 0,20 vs. 1,41 ± 0,27 vs. 0,95 ± 0,16, p = 0,021; SLC23A2: 5,61 ± 0,77 vs. 5,51 ± 1,21 vs. 11,66 ± 1,90, p = 0,018). CONCLUSIONES: Los genes reguladores de apoptosis (TP53) e integridad de la matriz extracelular (MMP9) podrían estar implicados en la susceptibilidad para el desarrollo/progresión de la RD, así como el gen SLC232A2 (transportador del ácido ascórbico) puede comportarse como protector del riesgo de padecer/progresar en la retinopatía

OBJECTIVE: To identify genes involved in the pathogenic mechanisms of non-proliferative diabetic retinopathy (NPDR), among which include oxidative stress, extracellular matrix changes, and/or apoptosis, in order to evaluate the risk of developing this retinal disease in a type2 diabetic (DM2) population. MATERIAL AND METHODS: A case-control study was carried out on 81 participants from the Valencia Study on Diabetic Retinopathy (VSDR) of both genders, with ages 25-85 years. They were classified into: (I) DM2 group (n = 49), with DR (+DR; n = 14) and without DR (-DR; n = 35), and (II) control group (GC; n = 32). The protocols included a personal interview, standardised ophthalmological examination, and blood collection (to analyse the DNA for determining the gene expression (TP53, MMP9, and SLC23A2) in the study groups. Statistical analyses were performed using the SPSS v22.0 program. RESULTS: The TP53 and MMP9 genes showed a higher expression in the DM2 group compared to the GC, although the difference was only significant for the MMP9 gene (TP53: 10.40 ± 1.20 V. 8.23 ± 1.36, P = .084; MMP9: 1.45 ± 0.16 vs. 0.95 ± 0.16, P = .036), and the SLC23A2 gene showed a significant lower expression in the DM2 vs CG (5.58 ± 0.64 vs. 11.66±1.90, P=.026). When sub-dividing the DM2 group according to the presence of retinopathy, the expression of the TP53, MMP9 and SLC23A2 genes showed significant differences between the DM2−RD, DM2+RD and GC groups (TP53: 9.95 ± 1.47 vs. 11.52 ± 2.05 vs. 8.23 ± 1.36, P = .038; MMP9: 1.47 ± 0.20 vs. 1.41 ± 0.27 vs. 0.95 ± 0.16, P = .021; SLC23A2: 5.61 ± 0.77 vs. 5.51 ± 1.21 vs. 11.66 ± 1.90, P = .018). CONCLUSIONS: Genes involved in extracellular matrix integrity (MMP9) and/or apoptosis (TP53), could be considered potential markers of susceptibility to the development/progression of NPDR. Interestingly, the SLC232A2 gene (ascorbic acid transporter) can be considered a protector of the risk of the development/progression of the retinopathy

Emerging insights into hypothalamic-pituitary-gonadal axis regulation and interaction with stress signalling.

Reproduction and fertility are regulated via hormones of the hypothalamic-pituitary-gonadal (HPG) axis. Control of this reproductive axis occurs at all levels, including the brain and pituitary, and allows for the promotion or inhibition of gonadal sex steroid secretion and function. In addition to guiding proper gonadal development and function, gonadal sex steroids also act in negative- and positive-feedback loops to regulate reproductive circuitry in the brain, including kisspeptin neurones, thereby modulating overall HPG axis status. Additional regulation is also provided by sex steroids made within the brain, including neuroprogestins. Furthermore, because reproduction and survival need to be coordinated and balanced, the HPG axis is able to modulate (and be modulated by) stress hormone signalling, including cortiscosterone, from the hypothalamic-pituitary-adrenal (HPA) axis. This review covers recent data related to the neural, hormonal and stress regulation of the HPG axis and emerging interactions between the HPG and HPA axes, focusing on actions at the level of the brain and pituitary.

Identification of new candidate genes for retinopathy in type 2 diabetics. Valencia Study on Diabetic Retinopathy (VSDR). Report number 3. / Identificación de nuevos genes candidatos para la retinopatía en diabéticos tipo 2. Estudio Valencia sobre Retinopatía Diabética (EVRD). Informe n.° 3.

OBJECTIVE: To identify genes involved in the pathogenic mechanisms of non-proliferative diabetic retinopathy (NPDR), among which include oxidative stress, extracellular matrix changes, and/or apoptosis, in order to evaluate the risk of developing this retinal disease in a type2 diabetic (DM2) population. MATERIAL AND METHODS: A case-control study was carried out on 81 participants from the Valencia Study on Diabetic Retinopathy (VSDR) of both genders, with ages 25-85years. They were classified into: (i)DM2 group (n=49), with DR (+DR; n=14) and without DR (-DR; n=35), and (ii)control group (GC; n=32). The protocols included a personal interview, standardised ophthalmological examination, and blood collection (to analyse the DNA for determining the gene expression (TP53, MMP9, and SLC23A2) in the study groups. Statistical analyses were performed using the SPSS v22.0 program. RESULTS: The TP53 and MMP9 genes showed a higher expression in the DM2 group compared to the GC, although the difference was only significant for the MMP9 gene (TP53: 10.40±1.20 vs. 8.23±1.36, P=.084; MMP9: 1.45±0.16 vs. 0.95±0.16, P=.036), and the SLC23A2 gene showed a significant lower expression in the DM2 vs CG (5.58±0.64 vs. 11.66±1.90, P=.026). When sub-dividing the DM2 group according to the presence of retinopathy, the expression of the TP53, MMP9 and SLC23A2 genes showed significant differences between the DM2-RD, DM2+RD and GC groups (TP53: 9.95±1.47 vs. 11.52±2.05 vs. 8.23±1.36, P=.038; MMP9: 1.47±0.20 vs. 1.41±0.27 vs. 0.95±0.16, P=.021; SLC23A2: 5.61±0.77 vs. 5.51±1.21 vs. 11.66±1.90, P=.018). CONCLUSIONS: Genes involved in extracellular matrix integrity (MMP9) and/or apoptosis (TP53), could be considered potential markers of susceptibility to the development/progression of NPDR. Interestingly, the SLC232A2 gene (ascorbic acid transporter) can be considered a protector of the risk of the development/progression of the retinopathy.

Gender-specific impairment of in vitro sinoatrial node chronotropic responses and of myocardial ischemia tolerance in rats exposed prenatally to betamethasone.

Excessive fetal glucocorticoid exposure has been linked to increased susceptibility to hypertension and cardiac diseases in the adult life, a process called fetal programming. The cardiac contribution to the hypertensive phenotype of glucocorticoid-programmed progeny is less known, therefore, we investigated in vitro cardiac functional parameters from rats exposed in utero to betamethasone. Pregnant Wistar rats received vehicle (VEH) or betamethasone (BET, 0.1mg/kg, i.m.) at gestational days 12, 13, 18 and 19. Male and female offspring were killed at post-natal day 30 and the right atrium (RA) was isolated to in vitro evaluation of drug-induced chronotropic responses. Additionally, whole hearts were retrograde-perfused in a Langendorff apparatus and infarct size in response to in vitro ischemia/reperfusion (I/R) protocol was evaluated. Male and female progeny from BET-exposed pregnant rats had reduced birth weight, a hallmark of fetal programming. Male BET-progeny had increased basal RA rate, impaired chronotropic responses to noradrenaline and adenosine, and increased myocardial damage to I/R. Though a 12-fold reduction in the negative chronotropic responses to adenosine, the effects of non-metabolisable adenosine receptor agonists 5'-(N-ethylcarboxamido)adenosine or 2-Chloro-adenosine were not different between VEH- and BET-exposed male rats. BET-exposed female offspring presented no cardiac dysfunction. Prenatal BET exposure engenders male-specific impairment of sinoatrial node function and on myocardial ischemia tolerance resulting, at least in part, from an increased adenosine metabolism in the heart. In light of the importance of adenosine in the cardiac physiology our results suggest a link between reduced adenosinergic signaling and the cardiac dysfunctions observed in glucocorticoid-induced fetal programming.

Multidrug-resistant pathogenic Escherichia coli isolated from wild birds in a veterinary hospital.

Wild birds are carriers of Escherichia coli. However, little is known about their role as reservoirs for extra-intestinal pathogenic E. coli (ExPEC). In this work we investigated E. coli strains carrying virulence genes related to human and animal ExPEC isolated from free-living wild birds treated in a veterinary hospital. Multidrug resistance was found in 47.4% of the strains, but none of them were extended-spectrum beta-lactamase producers. Not only the virulence genes, but also the serogroups (e.g. O1 and O2) detected in the isolates of E. coli have already been implicated in human and bird diseases. The sequence types detected were also found in wild, companion and food animals, environmental and human clinical isolates in different countries. Furthermore, from the 19 isolates, 17 (89.5%) showed a degree of pathogenicity on an in vivo infection model. The isolates showed high heterogeneity by pulsed-field gel electrophoresis indicating that E. coli from these birds are clonally diverse. Overall, the results showed that wild birds can be reservoirs and/or vectors of highly pathogenic and multidrug-resistant E. coli that have the potential to cause disease in humans and poultry.