Elevation provenance affects photosynthesis and its acclimation to temperature in the high-Andes alpine herb Phacelia secunda.

We analysed whether Phacelia secunda populations from different elevations exhibit intrinsic traits associated with diffusive and biochemical components of photosynthesis, and if they differ in acclimation of photosynthesis to warmer temperatures. We hypothesized that P. secunda will have similar photosynthetic performance regardless of altitudinal provenance and that plants from high elevations will have a lower photosynthetic acclimation capacity to higher temperature than plants from low elevations. Plants from 1600, 2800 and 3600 m a.s.l. in the central Chilean Andes were collected and grown under two temperature regimes (20/16 °C and 30/26 °C day/night). The following photosynthetic traits were measured in each plant for the two temperature regimes: AN , gs , gm , Jmax , Vcmax , Rubisco carboxylation kcat c . Under a common growth environment, plants from the highest elevation had slightly lower CO2 assimilation rates compared to lower elevation plants. While diffusive components of photosynthesis increased with elevation provenance, the biochemical component decreased, suggesting compensation that explains the similar rates of photosynthesis among elevation provenances. Plants from high elevations had lower photosynthetic acclimation to warmer temperatures compared to plants from lower elevations, and these responses were related to elevational changes in diffusional and biochemical components of photosynthesis. Plants of P. secunda from different elevations maintain photosynthetic traits when grown in a common environment, suggesting low plasticity to respond to future climate changes. The fact that high elevation plants had lower photosynthetic acclimation to warmer temperature suggests higher susceptibility to increases in temperature associated with global warming.

Human papillomavirus infections in low-grade squamous intraepithelial lesion in Peruvian pregnant woman: A cross-sectional cytology-based study.

Background and Aims: Low-risk human papillomaviruses (HPV) are important in pregnant women because they are risk factors for Condyloma acuminatum and recurrent respiratory papillomatosis in the newborn. On the other hand, HPV may contribute to the development of preneoplastic lesions such as LSIL in pregnant women. We aimed to assess the frequency of HPV infections in low-grade squamous intraepithelial lesion (LSIL) in Peruvian pregnant women. Methods: A cross-sectional study was conducted from 2011 to 2015 in 84 primiparous- and multiparous pregnant women (mean age: 27 ± 6.3 years). Pregnant women of 18-45 years attending gynecology outpatient department were included for the study. LSIL and HPV (nuclear irregularities, koilocytosis, and cytopathic effect) cellular alterations were reported using the Bethesda System guidelines. Results: Sixty-four percent had cytological HPV infection (koilocytes and/or pathognomonic signs of infection) and more than a half of pregnant women had a previous Pap test. LSIL was more frequent in multiparous (increased by 12%, p = 0.008), in the second and third trimester (60.7%, p = 0.002), and between the ages of 18 and 30 (42 cases (50%), p = 0.110). This proportion was significatively increased in women with ≥2 sexual partners (39.3%), with an early onset of first intercourse, and from the Rímac Municipality (14.3%) (p < 0.05). The rate of pregnant women with HPV infection increased by 39% between 2011 and 2015 (p = 0.001). Conclusion: Peruvian pregnant women with LSIL have a high frequency of HPV infections. These young pregnant women (≤30 years of age), with multiple pregnancy, ≥2 sexual partners, and early onset of sexual intercourse were mainly associated with the third trimester HPV infection and LSIL. To detect early lesions of the cervix, it is key to continue monitoring HPV infections with molecular techniques and screening in pregnant women.

The Absence of Caspase-8 in the Dopaminergic System Leads to Mild Autism-like Behavior.

In the last decade, new non-apoptotic roles have been ascribed to apoptotic caspases. This family of proteins plays an important role in the sculpting of the brain in the early stages of development by eliminating excessive and nonfunctional synapses and extra cells. Consequently, impairments in this process can underlie many neurological and mental illnesses. This view is particularly relevant to dopamine because it plays a pleiotropic role in motor control, motivation, and reward processing. In this study, we analyze the effects of the elimination of caspase-8 (CASP8) on the development of catecholaminergic neurons using neurochemical, ultrastructural, and behavioral tests. To do this, we selectively delete the CASP8 gene in cells that express tyrosine hydroxylase with the help of recombination through the Cre-loxP system. Our results show that the number of dopaminergic neurons increases in the substantia nigra. In the striatum, the basal extracellular level of dopamine and potassium-evoked dopamine release decreased significantly in mice lacking CASP8, clearly showing the low dopamine functioning in tissues innervated by this neurotransmitter. This view is supported by electron microscopy analysis of striatal synapses. Interestingly, behavioral analysis demonstrates that mice lacking CASP8 show changes reminiscent of autism spectrum disorders (ASD). Our research reactivates the possible role of dopamine transmission in the pathogenesis of ASD and provides a mild model of autism.

Impact of the Management and Proportion of Lost to Follow-Up Cases on Cancer Survival Estimates for Small Population-Based Cancer Registries.

BACKGROUND: Estimation of survival requires follow-up of patients from diagnosis until death ensuring complete and good quality data. Many population-based cancer registries in low- and middle-income countries have difficulties linking registry data with regional or national vital statistics, increasing the chances of cases lost to follow-up. The impact of lost to follow-up cases on survival estimates from small population-based cancer registries (<500 cases) has been understudied, and bias could be larger than in larger registries. METHODS: We simulated scenarios based on idealized real data from three population-based cancer registries to assess the impact of loss to follow-up on 1-5-year overall and net survival for stomach, colon, and thyroid cancers-cancer types with very different prognosis. Multiple scenarios with varying of lost to follow-up proportions (1-20%) and sample sizes of (100-500 cases) were carried out. We investigated the impact of excluding versus censoring lost to follow-up cases; punctual and bootstrap confidence intervals for the average bias are presented. RESULTS: Censoring of lost to follow-up cases lead to overestimation of the overall survival, this effect was strongest for cancers with a poor prognosis and increased with follow-up time and higher proportion of lost to follow-up cases; these effects were slightly larger for net survival than overall survival. Excluding cases lost to follow-up did not generate a bias on survival estimates on average, but in individual cases, there were under- and overestimating survival. For gastric, colon, and thyroid cancer, relative bias on 5-year cancer survival with 1% of lost to follow-up varied between 6% and 125%, 2% and 40%, and 0.1% and 1.0%, respectively. CONCLUSION: Estimation of cancer survival from small population-based registries must be interpreted with caution: even small proportions of censoring, or excluding lost to follow-up cases can inflate survival, making it hard to interpret comparison across regions or countries.

Bioconversion of polyphenols and organic acids by gut microbiota of predigested Hibiscus sabdariffa L. calyces and Agave (A. tequilana Weber) fructans assessed in a dynamic in vitro model (TIM-2) of the human colon.

The present work aimed at understanding gut microbiota bioconversion of phenolic compounds (PC) and organic acids in predigested Hibiscus sabdariffa (Hb) calyces and the mixture of Hb and Agave (Agave tequilana Weber) fructans (AF). With this purpose, dried Hb and Hb/AF were predigested with enzymatic treatment, and then fermented in a dynamic in vitro model of the human colon (TIM-2). After HPLC-ESI-QToF-MS analysis of samples taken at 0, 24, 48 and 72 h of fermentation, it was observed that hydroxycinnamic acids, flavanols, flavonols, and anthocyanins were mainly transformed into derivatives of hydroxyphenylpropionic, hydroxyphenylacetic and hydroxybenzoic acids. Moreover, organic acids, such as hydroxycitric and hibiscus acids, were formed along with unidentified lactones and reduced compounds. Interestingly, no differences were observed between microbial-derived metabolites formed after the fermentation of Hb and Hb/AF. In conclusion, colonic fermentation of polyphenol-rich Hb yields a wide range of microbial phenolic metabolites with potential effects on health.

Tratamiento quirúrgico de la gangrena de Fournier / Surgical management of Fournier's gangrene

Resumen Objetivo: Describir el manejo quirúrgico realizado para la reconstrucción genitoperineal (RGP) en pacientes con secuelas de Gangrena de Fournier (GF). Materiales y Método: Corresponde a una serie de casos retrospectiva de pacientes con secuelas de GF a los que se les realizó RGP entre los años 2011 y 2019. Se realizó un análisis descriptivo con las variables de técnica quirúrgica, edad, sexo, comorbilidades, subunidades anatómicas afectadas, origen anatómico de la gangrena de Fournier, número de procedimientos quirúrgicos, procedimiento de colostomía, terapia de presión negativa, Flexi-Seal®, bacterias aisladas, duración de estancia hospitalaria, tipo de procedimientos reconstructivos y complicaciones. Resultados: Se realizó RGP a 43 pacientes (81,1% hombres), con un promedio de edad de 59,1 (17-86 años), 72,7% eran diabéticos. El número de subunidades involucradas se asocia directamente y significativamente en relación al número de intervenciones quirúrgicas. Las técnicas utilizadas para la reconstrucción en orden de frecuencia fueron: colgajos (23%), cierre parcial más injerto dermoepidérmico de grosor parcial (IPP) (20%), cierre parcial (16%) e IPP (16%), cierre por segunda intención (10%), colgajo más IPP (7%) y cierre parcial para cierre por segunda intención de zona restante (5%). Discusión: La elección de reconstrucción se basa en las características del defecto, es decir, el tamaño, la ubicación y profundidad, así como la disponibilidad de tejido local. De preferencia optar por cierres primarios sin tensión, seguido de colgajos y de IPP. Conclusión: La RGP es un desafío para el cirujano plástico. Las técnicas descritas han demostrado ser seguras y reproducibles para el tratamiento quirúrgico de la gangrena de Fournier.

Aim: To describe the surgical management performed for genital-perineal reconstruction (GPR) in patients with sequelae of Fournier gangrene (FG). Materials and Method: It is based on a retroactive series of cases of patients with effects of FG who were given GPR between 2011 and 2019. We performed a descriptive analysis using the variables surgical technique, age, sex, comorbidities, anatomical subunits affected, anatomic origin of the Fournier's gangrene, number of surgical procedures, colostomy procedure, negative pressure therapy, Flexi-Seal®, bacteria isolated, hospital stay, type of reconstructive procedures and complications. We performed GPR on 43 patients (81.1% male), with a mean age of 59.1 (17-86 years); 72% were diabetic. The number of subunits involved was directly and significantly associated with the number of surgical interventions. Results: The reconstruction techniques most used were, in descending order: flaps (23.2%), wound closure and split-thickness skin graft (STSG) (23.2%), primary closure (16.2%), STSG (16.2%), secondary closure (9.3%), flap and STSG (6.9%) and partial wound closure for healing of the remaining area for a second intention (4.6%). Discussion: The reconstruction choice is based on the characteristics of the defect, that is, the size, location and depth, as well as the availability of local tissue. Preferably opt for primary closures without tension, followed by flaps and IPP. Conclusion: The RGP is a challenge for the plastic surgeon. The techniques described have proven safe and reproducible for the surgical treatment of Fournier Gangrene.

Bioconversion by gut microbiota of predigested mango (Mangifera indica L) 'Ataulfo' peel polyphenols assessed in a dynamic (TIM-2) in vitro model of the human colon.

Gut microbiota bioconversion of polyphenols in predigested mango 'Ataulfo' peel was studied using a validated, dynamic in vitro human colon model (TIM-2) with faecal microbial inoculum. Dried peels were predigested with enzymatic treatment, followed by TIM-2 fermentation (72 h). Samples were taken at 0, 24, 48 and 72 h and analyzed by HPLC-QToF. Derivatives of hydroxyphenylpropionic, hydroxyphenylacetic and hydroxybenzoic acids, as well as, pyrogallol were the main polyphenols identified. These metabolites might derivate from flavonoid (flavanols and flavonols), gallate and gallotannin biotransformation. Despite the high content of ellagic acid in mango peel, low amounts were detected in TIM-2 samples due to transformation into urolythins A and C, mainly. Xanthone and benzophenone derivatives, specific to mango, remained after the colonic biotransformation, contrary to flavonoids, which completely disappeared. In conclusion, microbial-derived metabolites, such as xanthone and benzophenone derivatives, among others, are partially stable after colonic fermentation, and thus have the potential to contribute to mango peel bioactivity.

Outcomes in patients receiving fixed-dosed aflibercept for treatment-naïve neovascular age-related macular degeneration during one year of routine clinical practice. / Aflibercept intravítreo en dosis fijas en pacientes naïve con degeneración macular asociada a la edad neovascular: resultados a un año en práctica clínica real.

OBJECTIVE: To investigate the visual and anatomical outcomes of aflibercept as therapy in patients with treatment-naïve neovascular age-related macular degeneration during one year in routine clinical practice. METHODS: The study was a retrospective, case series, including 35 patients, 38 eyes, with neovascular age-related macular degeneration that received aflibercept injections (Eylea®). Patients received a loading dose of 3monthly injections (2mg / 0.05ml) followed by intravitreal injections every 2 months. RESULTS: At 3 and 12 months, the mean best-corrected visual acuity improved significantly as compared with baseline (ETDRS 50.5±14.5 and 53.1±14.5 vs. 39.6±14.7, respectively, P<.05). At 3 and 12 months, the proportion of patients who improved visual acuity by ≥15 letters was 37.1% and 45.7%, respectively. The mean decrease in central macular thickness was also significant after loading dose (239.6±52.0µm) and at 12 month (227±53.2µm) compared with pre-treatment values (370.3±117, 6) (P<.001). Resolution of pigment epithelial detachment (PED) was also observed in 14 out of 20 (70%) eyes with PED at baseline. CONCLUSION: Aflibercept administered by fixed dosing over one year improved visual acuity and macular morphology in treatment-naïve eyes in routine daily practice.

Epidemiology and control measures of an OXA-48-producing Enterobacteriaceae hospital-wide oligoclonal outbreak.

The main objective of our study was to describe the epidemiological and microbiological features of an oligoclonal hospital-wide outbreak caused by OXA-48-producing Enterobacteriaceae (OXA-48-PE). OXA-48 is a carbapenemase belonging to Ambler class D beta-lactamases, identified frequently in the Mediterranean and Southern European countries, and associated with several Enterobacteriaceae species. An outbreak of OXA-48-PE with a complex epidemic pattern was detected in January 2011. Initial control measures included contact precautions and the reinforcement of infection control practices, but despite all efforts made, the epidemiological situation hardly changed and new measures were implemented during 2013. An observational retrospective study was performed to describe the main features of the outbreak and to analyse the cumulative incidence (CI) trends. Eight hundred and 16 patients colonised or infected by OXA-48-PE were identified during the 2-year period (January 2013-December 2014), female 46%, mean age (s.d.), 71.6 (15.2). The samples isolated in the incident cases were rectal swabs (80%), urine samples (10.7%), blood samples (2.8%) and other clinical samples (6.6%). The most frequent OXA-48-PE was Klebsiella pneumoniae. Eleven different clones were identified, but K. pneumoniae sequence types 11 and 405 were predominant: ST11 (64.2%) and ST405 (29.3%). OXA-48-PE CI trend suffered a statistically significant change in August 2013, which continued the following months. Though we could not eradicate the outbreak, we observed a statistically significant drop in CI after an intervention for OXA-48-PE control, based on patient cohort, active surveillance, electronic alerts and reinforcement of infection control measures in a tertiary hospital.

Effects of S 38093, an antagonist/inverse agonist of histamine H3 receptors, in models of neuropathic pain in rats.

BACKGROUND: Histamine H3 receptors are mainly expressed on CNS neurons, particularly along the nociceptive pathways. The potential involvement of these receptors in pain processing has been suggested using H3 receptor inverse agonists. METHODS: The antinociceptive effect of S 38093, a novel inverse agonist of H3 receptors, has been evaluated in several neuropathic pain models in rat and compared with those of gabapentin and pregabalin. RESULTS: While S 38093 did not change vocalization thresholds to paw pressure in healthy rats, it exhibited a significant antihyperalgesic effect in the Streptozocin-induced diabetic (STZ) neuropathy model after acute and chronic administration and, in the chronic constriction injury (CCI) model only after chronic administration, submitted to the paw-pressure test. Acute S 38093 administration at all doses tested displayed a significant cold antiallodynic effect in a model of acute or repeated administration of oxaliplatin-induced neuropathy submitted to cold tail immersion, cold allodynia being the main side effect of oxaliplatin in patients. The effect of S 38093 increased following chronic administration (i.e. twice a day during 5 days) in the CCI and STZ models except in the oxaliplatin models where its effect was already maximal from the first administration The kinetics and size of effect of S 38093 were similar to gabapentin and/or pregabalin. Finally, the antinociceptive effect of S 38093 could be partially mediated by α2 adrenoreceptors desensitization in the locus coeruleus. CONCLUSIONS: These results highlight the interest of S 38093 to relieve neuropathic pain and warrant clinical trials especially in chemotherapeutic agent-induced neuropathic pain. SIGNIFICANCE: S 38093, a new H3 antagonist/inverse agonist, displays antiallodynic and antihyperalgesic effect in neuropathic pain, especially in oxaliplatin-induced neuropathy after chronic administration. This effect of S 38093 in neuropathic pain could be partly mediated by α2 receptors desensitization in the locus coeruleus.

Physiological and ultrastructural characterisation of a desiccation-tolerant filmy fern, Hymenophyllum caudiculatum: Influence of translational regulation and ABA on recovery.

The filmy fern Hymenophyllum caudiculatum can lose 60% of its relative water content, remain dry for some time and recover 88% of photochemical efficiency after 30 min of rehydration. Little is known about the protective strategies and regulation of the cellular rehydration process in this filmy fern species. The aim of this study was to characterise the filmy fern ultrastructure during a desiccation-rehydration cycle, and measure the physiological effects of transcription/translation inhibitors and ABA during desiccation recovery. Confocal and transmission electron microscopy were used to compare changes in structure during fast or slow desiccation. Transcription (actinomycin D) and translation (cycloheximide) inhibitors and ABA were used to compare photochemical efficiency during desiccation recovery. Cell structure was conserved during slow desiccation and rehydration, constitutive properties of the cell wall, allowing invagination and folding of the membranes and an important change in chloroplast size. The use of a translational inhibitor impeded recovery of photochemical efficiency during the first 80 min of rehydration, but the transcriptional inhibitor had no effect. Exogenous ABA delayed photochemical inactivation, and endogenous ABA levels decreased during desiccation and rehydration. Frond curling and chloroplast movements are possible strategies to avoid photodamage. Constitutive membrane plasticity and rapid cellular repair can be adaptations evolved to tolerate a rapid recovery during rehydration. Further research is required to explore the importance of existing mRNAs during the first minutes of recovery, and ABA function during desiccation of H. caudiculatum.

Misdiagnoses of Epilepsy as Ekbom Syndrome, Mood Instability, and Nocturnal Visual Hallucinations.

Epileptic seizures may be misdiagnosed if they manifest as psychiatric symptoms. We report three female patients with no preexisting history of epilepsy that were unsuccessfully treated as primary psychiatric disorder: one patient was initially diagnosed with somatization and Ekbom syndrome; the second was referred to psychiatrist due to mood instability and visual hallucinations; and the third one was referred for anxiety and hallucinations related to sleep. A carefully taken medical history clarified diagnoses of epilepsy. None of the patients responded to medications aimed at treating psychiatric symptoms, and all the patients had favorable response to antiepileptic treatment. These cases illustrate that epileptic patients may experience nonconvulsive seizures that might be misdiagnosed as primary psychiatric disorder.

Antiproliferative and cytotoxic effects of green coffee and yerba mate extracts, their main hydroxycinnamic acids, methylxanthine and metabolites in different human cell lines.

This work aimed at studying the effects of green coffee bean (GCBE) and yerba mate (YME) extracts, their main phenolic components (5-caffeoylquinic acid, 5-CQA; 3,5-dicaffeoylquinic acid, 3,5-DCQA) and metabolites (ferulic acid, FA; caffeic acid, CA; dihydrocaffeic acid, DHCA; and dihydroferulic acid, DHFA) along with caffeine (CAF) on the viability and proliferation of different human cell lines. Extracts (10-1000 µg/mL) and standards (10-1000 µM) were assayed in colon (Caco-2), lung (A549), oesophageal (OE-33), urinary bladder (T24) human carcinoma cells, and a non-cancer cell line (CCD-18Co). YME significantly reduced viability of cancer cells at all assayed concentrations, the higher doses also reducing cell proliferation. GCBE effects on cell viability were more effective at 100 and 1000 µg/mL, showing modest effects on cell proliferation. The highest doses of 5-CQA and 3,5-DCQA reduced cell viability and proliferation in all cell lines, whereas FA, DHCA and DHFA had lower and variable effects. Caffeine had no effect. Dietary-attainable concentrations (0.1, 1 and 10 µg/mL) of YME were tested for cytotoxicity and reactive oxygen species generation, showing no cytotoxic effect. Low concentrations of all tested compounds were non-cytotoxic to CCD-18Co cells. CONCLUSION: YME and to a lower degree GCBE, their phenolic components and metabolites may decrease cancer cell viability and proliferation.