Role of IL33 in chronic inflammation and microvascular damage as a reflection of organ damage on a cohort of patients with acromegaly.

AIM: Acromegaly is a rare chronic disease, caused by the over-secretion of growth hormone (GH), that creates a pro-inflammatory state, but the exact mechanisms by which GH or insulin-like growth factor 1 (IGF-1) act on inflammatory cells are not fully understood. Aim of the study was to evaluate Interleukin-33 (IL33) and the skin perfusion of hands in patients with acromegaly (AP) and healthy controls (HC). METHODS: IL33 have been assessed in 40 AP and 40 HC. IL 33 was determined and skin perfusion of hands was assessed by laser speckle contrast analysis (LASCA) in both populations. RESULTS: IL33 was significantly higher in AP compared to HC [45.72 pg/ml (IQR 28.74-60.86) vs 14 pg/ml (IQR 6.5535); p < 0.05]. At LASCA, peripheral blood perfusion (PBP) was significantly lower in AP compared to HC [53.39 pU (IQR 40.94-65.44) vs 87 pU (IQR 80-98) p < 0.001]. The median values of ROI1, ROI2 and ROI3 were significantly lower in AP compared to HC [97.32 pU (IQR 50.89-121.69) vs 131 pU (IQR 108-135); p < 0.001], [58.68 pU (IQR 37.72-84.92) vs 83 pU (IQR 70-89), p < 0.05] and HC [52.16 (34.47-73.78) vs 85 (78-98), p < 0.001], respectively. The proximal-distal gradient (PDG) was observed in 18 of 40 (45%) AP. CONCLUSION: Serum IL33 is higher in AP compared to HC; conversely a reduction of PBP of hands was present in AP compared to HC, probably due to endothelial dysfunction, strictly dependent on acromegaly and are not influenced by the choice of treatment.

Under-reporting of subjective symptoms and its prognostic value: a pooled analysis of 12 cancer clinical trials.

BACKGROUND: Oncologists tend to under-report subjective symptoms during cancer treatment. This study describes the under-reporting rate of selected symptoms and explores its association with overall survival (OS). A secondary aim is to test the association of patient-reported symptoms with OS. PATIENTS AND METHODS: This is a post hoc analysis on data pooled from 12 randomized trials, promoted by the National Cancer Institute of Naples (Italy), enrolling patients between 2002 and 2019, with published primary analyses. Occurrence and grade of six side-effects (anorexia, nausea, vomiting, constipation, diarrhea and fatigue) reported by physicians were compared with corresponding symptoms reported by patients in quality-of-life (QoL) questionnaires. Under-reporting was defined as the rate of cases reported grade 0 by the physician while grade ≥1 by the patient. Prognostic value was tested in a multivariable model stratified by trial, including age, sex and performance status as confounders. A landmark threshold was defined for OS analyses. RESULTS: 3792 patients with advanced lung, ovarian, pancreatic, breast or colorectal cancer were pooled; 2603 (68.6%) were eligible having at least one toxicity assessment and one QoL questionnaire, before the first planned disease restaging. Concordance between physicians' and patients' reporting was low with Cohen's k coefficients ranging from 0.03 (fatigue) to 0.33 (vomiting). Under-reporting ranged from 52.7% (nausea) to 80.5% (anorexia), and was not associated with OS. Patient-reported anorexia, vomiting and fatigue ('a little' or more) were significantly associated with shorter OS. CONCLUSIONS: Under-reporting of treatment side-effects is frequent, but it does not affect OS. Patients' reported symptoms should be used for prognostic evaluation.

Effectiveness of a digital application to improve stroke knowledge for kids / Efectividad de una aplicación móvil para mejorar el conocimiento sobre los síntomas de ictus en una población pediátrica de Colombia

Introduction: Stroke is highly prevalent in Latin America and one of the leading causes of morbidity and mortality in the world. Educating children about stroke has been established as an effective method to detect symptoms early, reduce hospital visits, and raise awareness among adults. Objective: To analyze the effectiveness of a mobile application to improve knowledge and understanding of stroke among children. Method: We conducted a focus group session including 12 children in order to analyze the behavior of 6 questions previously validated by expert neurologists. Subsequently, 105 primary school students between the ages of 7 and 12 completed a questionnaire on stroke symptoms and how to contact the emergency services before and after using an application on stroke symptoms. Qualitative analyses and the Student t test were used to verify the existence of differences between pre- and post-intervention test results. Results: After a single 40-min working session with the application, between 50% and 67% of the children were able to identify the signs of stroke, and 96.2% knew the national emergency services telephone number. Statistical analysis revealed statistically significant differences before and after the intervention with the digital application (t = 19.54; p < 0.001) and intragroup differences in the post-intervention test results (t = 40.71; p < 0.001). Conclusion: Primary school children who used our digital application increased their knowledge, understanding, and learning of stroke symptoms.(AU)

Introducción: El ictus es muy prevalente en Latinoamérica y constituye una de las principales causas de morbimortalidad a nivel mundial. Se ha sugerido que enseñar a los niños a reconocer los primeros síntomas de ictus puede ayudar a reducir el número de ingresos por esta enfermedad y a concienciar a la población adulta. Objetivo: Analizar la efectividad de una aplicación móvil para aumentar el conocimiento del ictus en los niños. Método: Llevamos a cabo una sesión con un grupo focal de 12 niños para analizar el comportamiento de 6 preguntas previamente validadas por un grupo de neurólogos expertos. Posteriormente, administramos un cuestionario sobre síntomas de ictus y servicios de emergencias a 105 niños de entre 7 y 12 años en dos momentos diferentes: antes y después de usar la aplicación sobre síntomas de ictus. Se realizaron análisis cualitativos y se aplicó la prueba t de Student para confirmar la presencia de diferencias en las respuestas al cuestionario antes y después de la intervención. Resultados: Tras una única sesión de 40 minutos con la aplicación, entre el 50% y el 67% de los niños eran capaces de identificar los síntomas de ictus y el 96,2% se sabían el número de teléfono de emergencias. El análisis estadístico reveló diferencias estadísticamente significativas entre los resultados del cuestionario antes y después de la intervención (t = 19,54; P < 0,001), así como diferencias intragrupo en los resultados postintervención (t = 40,71; P < 0,001). Conclusión: Los niños que utilizaron nuestra aplicación acabaron sabiendo más sobre los síntomas de ictus y cómo actuar.(AU)

Prazosin blocks the glutamatergic effects of N-methyl-D-aspartic acid on lordosis behavior and luteinizing hormone secretion in the estrogen-primed female rat

We have observed that intracerebroventricular (icv) injection of selective N-methyl-D-aspartic acid (NMDA)-type glutamatergic receptor antagonists inhibits lordosis in ovariectomized (OVX), estrogen-primed rats receiving progesterone or luteinizing hormone-releasing hormone (LHRH). When NMDA was injected into OVX estrogen-primed rats, it induced a significant increase in lordosis. The interaction between LHRH and glutamate was previously explored by us and another groups. The noradrenergic systems have a functional role in the regulation of LHRH release. The purpose of the present study was to explore the interaction between glutamatergic and noradrenergic transmission. The action of prazosin, an alpha1- and alpha2b-noradrenergic antagonist, was studied here by injecting it icv (1.75 and 3.5 µg/6 µL) prior to NMDA administration (1 µg/2 µL) in OVX estrogen-primed Sprague-Dawley rats (240-270 g). Rats manually restrained were injected over a period of 2 min, and tested 1.5 h later. The enhancing effect induced by NMDA on the lordosis/mount ratio at high doses (67.06 ± 3.28, N = 28) when compared to saline controls (6 and 2 µL, 16.59 ± 3.20, N = 27) was abolished by prazosin administration (17.04 ± 5.52, N = 17, and 9.33 ± 3.21, N = 20, P < 0.001 for both doses). Plasma LH levels decreased significantly only with the higher dose of prazosin (1.99 ± 0.24 ng/mL, N = 18, compared to saline-NMDA effect, 5.96 ± 2.01 ng/mL, N = 13, P < 0.05). Behavioral effects seem to be more sensitive to the alpha-blockade than hormonal effects. These findings strongly suggest that the facilitatory effects of NMDA on both lordosis and LH secretion in this model are mediated by alpha-noradrenergic transmission.

Thyrotropin releasing hormone injected into the nucleus accumbens septi selectively increases face grooming in rats

The effect of unilateral injection of peptides into the nucleus accumbens septi (NAS) on subcategories of grooming behavior was studied in male rats. The peptides used were: thyrotropin releasing hormone (TRH), luteinizing hormone releasing hormone (LHRH) and corticotropin releasing hormone (CRH). Male rats (Holtzman strain, 240-270 g body weight) injected with progressive doses of TRH (100, 200 and 400 ng) at 5-day intervals were compared with the control state (injection of artificial cerebrospinal fluid CSF). A selective increase in face grooming was observed with the 100 ng (49.78 + 6.11, N = 18) and 200 ng (50.29 + 7.72, N = 17) doses of TRH (P<0.05 vs CSF injection 26.94 + 3.64, N = 18). Face grooming increased further with the 400 ng dose (55.19 + 8.26, N = 16, P<0.01), but a dose-response curve could not be obtained at the dose range used. Flank scratching, head, body and genital grooming were not altered by the TRH injection, but the rearing behavior was inhibited (10.33 + 1.56; N = 18; 10.76 + 1.77, N = 17; 12 + 2.06, N = 16) (P<0.05 for all doses vs controls, 20.61 + 2.81, N = 18). The rats that received LHRH (75 ng, N = 16) and CRH (100 ng, N = 14) did not show behavioral changes when compared with their control states. The results show that injection on TRH into the NAS, but not the injection of LHRH or CRH, selectively increases face grooming without affecting other subcategories of grooming at the doses used, and appears to link this peptide with the neural substrate of stereotyped behavior.

Distinct grooming patterns induced by intracerebroventricular injection of CRH, TRH and LHRH in male rats

This paper reports the effects on grooming, related behaviors and levels of anxiety induced by the hypophysiotropic peptides corticotropin-releasing hormone (CRH, 1 mug, 0.2 nmol, icv), thyrotropin-releasing hormone (TRH, 100 mug, 275 nmol, icv) and luteinizing hormone-releasing hormone (LHRH, 1.5 mug, 1.3 nmol, icv) administered into the lateral ventricle of the brain (icv) of adult male rats of a Holtzman-derived colony (N = 15, each group). CRH induced an increase in total grooming scores, whereas LHRH, TRH and vehicle had no effect. CRH strongly increased face and head grooming and induced head shakes. The time spent in rearing and gnawing was significantly decreased. In the plus-maze, CRH reduced the time of exploration in the open arm. TRH increased face grooming and induced body shakes. LHRH had no effect on grooming or rearing behavior. No body or head shakes were observed after LHRH administration. Scoring of individual grooming elements demonstrated differences in action of the three peptides. Although both CRH and TRH increased face grooming, only CRH induced head grooming. Furthermore, CRH induced predominantly head shakes while TRH increased body shake activity. In contrast, CRH was anxiogenic and TRH appeared to induce stereotyped behavior. From the characterization of grooming elements and related responses, we conclude that each hypophysiotropic peptide induces a specific behavioral pattern.