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The prognosis of relapsed/refractory (R/R) neuroblastoma (NB) is dismal, calling for new therapeutic strategies. Venetoclax (VEN) is a highly selective, potent, orally bioavailable, BCL-2 inhibitor small-molecule that showed a synergistic effect with cyclophosphamide and topotecan (Cy-Topo) in murine NB models. Our aim was to evaluate the feasibility of VEN plus Cy-Topo in children with R/R NB. Four patients, who had previously failed > 3 lines of treatment, were treated with VEN plus Cy-Topo based on a 28-day schedule in an outpatient setting. BCL-2 expression in immunochemistry on tumor samples at relapse and the BCL2 gene status was evaluated in all patients. The main toxicity was hematological, with grade 4 neutropenia and thrombocytopenia occurring in all courses and leading to transient VEN discontinuation. Grade 3 oral mucositis was observed in 1/8 courses. No other grade 2-4 toxicities were observed. BCL-2 was expressed in all tumors, while no molecular abnormalities in the BCL-2 genes were detected. A stable disease was observed in all patients, without any progression during the study period. VEN plus Cy-Topo is well tolerated, with encouraging results that may be improved by testing the schedule in less advanced patients., (© 2023. The Author(s).)

Research has shown that violent ideations (VIs) may play a key role in aggression and violence. However, there is no tool to measure this construct adapted to the Spanish language so far. The current study aims to translate and evaluate the psychometric properties of the Violent Ideations Scale (VIS) in European Spanish. This study counts with a convenience sample of 752 native Spaniards or Spanish speakers residing in Spain, between 18- and 75-years old, 53% identified as female and 47% identified as male. The dimensionality, gender measurement invariance, concurrent validity and reliability of scores were assessed. Initial evidence of external validity was collected. Results confirmed the unidimensionality of the instrument. Measurement invariance held across females and males and reliabilities were high. VIS-ES scores correlated with aggressive behavior during the previous month. The VIS-ES seems suitable for use in non-clinical Spanish speaking samples., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The distal relationship between risk factors in childhood and subsequent dating violence in late adolescence has not often been explored using longitudinal data. This study aims to shed light on the problem of dating violence by examining children's backgrounds at age 7 and the link to the future involvement in dating violence at age 17 using the first and seventh waves of the Zurich Project on the Social Development from Childhood to Adulthood (z-proso, n = 644). The sample consists of 644 multiethnic adolescents (57.14% female, M = 17.47, SD = 0.37), mainly Swiss-born (90%), though more than half of their parents (60%) were born in another country. A latent class analysis was applied to identify three different profiles (a) zero (or minimal) involvement in teen dating violence, (b) perpetrators/victims of controlling behaviors, and (c) perpetrators/victims of controlling behaviors and of physical violence. Participants who were corporally punished and/or victims of bullying at age 7 were significantly more likely to belong to the controlling and physical violence profile than children in the non-violent class. These results suggest a certain chronicity of the effects of violent experiences in early childhood on the patterns of romantic relationships at 17 years old., (© 2022. The Author(s).)

The interventions used to prevent or treat violence against children, particularly sexual abuse, tend to only consider the target audience as their main source of data. We tested the effect of an online training for school staff members in Europe through three studies. In Study I, we interviewed 5 adult women (Mage = 49.2, SD = 5.81) who were victims of sexual abuse during childhood to assess what school could have done during that time to protect them. Through Study II, we collected data on 66 school staff members to assess feasibility (based on quantitative indicators) and to explore the changes they would make to their everyday practice due to the training course (using qualitative analysis). In Study III, we used network analysis to assess to what extent the actions described by school staff in Study II met the needs expressed by the victims in Study I. Findings of Study I revealed new proposals from the victims' perspective, such as working with the perpetrators. Study II showed the feasibility of training and identified five types of action that school staff members will include in their everyday working dynamics due to the training: detection (e.g., Greater attention to relationships with peers), reporting (e.g., Now I know that suspecting a case of child abuse is enough to report), everyday practices (e.g., Introducing a calming space), changes at school level (e.g., Propose the training course to the school management team) or practices that could belong to more than one category (e.g., Greater awareness of the activities undertaken by the school). Study III provided evidence that some of these changes (e.g., reporting without looking for proof) were in line with some of the victims' expectations (e.g., listen to the children). We also identified gaps that need to be further developed., Competing Interests: The authors have declared that no competing interests exist.

Even though classic effect size measures (e.g., Pearson's r, Cohen's d) are widely applied in social sciences, the threshold used to interpret them is somewhat arbitrary. This study proposes necessary condition analysis (NCA) to complement traditional methods. We explain NCA in light of the current limitations of classical techniques, highlighting the advantages in terms of interpretation and translation into practical terms and recognizing its weaknesses. To do so, we provide an example by testing the link between three independent variables with a relevant outcome in a sample of 235 subjects. The traditional Pearson's coefficient was obtained, and NCA was used to test if any of the predictors were necessary but not sufficient conditions. Our study also obtains outcome and condition inefficiency as well as NCA bottlenecks. Comparison and interpretation of the traditional and NCA results were made considering recommendations. We suggest that NCA can complement correlation analyses by adding valuable and applicable information, such as if a variable is needed to achieve a certain outcome level and to what degree.

Schools are in a position to connect children and adolescents suspected of being victims of violence with an external source of support by making referrals to external agencies. However, several studies have identified obstacles that hinder early reporting among school staff members. Very few studies have applied a mixed-method approach to try to understand this sensitive issue. The current study used this approach to analyze to what extent the students suspected of being victimized match the ones reported by active school staff members in Spain ( n = 453, 83.5% females, age: M = 42.23, SD = 9.46). We classified the reasons given for not reporting the potential victimization cases encountered and made comparisons to determine whether there were differences in the level of knowledge, or in the sociodemographic characteristics, of respondents who gave different reasons for not reporting. Although 73.5% of school staff members had detected at least one potential case, 40.8% of them referred it to an external agency. The most common reasons for lack of reporting included deciding not to do so once concerns had been shared within the school and believing that one must be certain or that only serious violence should be reported. The findings of this study may help to further understand the decisions not to report certain suspicions of potential victimization cases to external agencies by school staff. There is an urgent need to raise awareness about the duty to report these concerns to external agencies, even in the absence of agreement from the school management team. Members of school staff need to be strongly encouraged to become familiar with the existing protocols.

Background: The aim of this paper is to illustrate the use of a modified vertical holding appliance (G-VHA) to obtain the vertical control of maxillary molars and tongue stimulation in order to achieve a transverse activation in growing patients with dental open bite without the patient's compliance., Case Reports: The G-VHA is a modified trans-palatal bar with a resin pad covering the Omega central loop and two adjunctive lateral loops to ensure the bar flexibility. The G-VHA is designed to direct the force of the tongue against the upper molars to generate intrusion and at the same time to stimulate and re-educate the tongue. Two cases of dental open bite in growing patients are illustrated. Both patients were successfully treated, and the open bite was fully corrected thanks to molar intrusion, following counterclockwise rotation of the mandible and tongue correction. Finishing of alignment was performed in phase II of the treatment with conventional appliances., Conclusion: The G-VHA proved to be effective in controlling the vertical position of maxillary molars promoting the counter-clockwise rotation of the mandible and stimulating a different tongue posture.

Knowledge of child victimization among school staff is believed to affect the detection and reporting of potential cases in the school environment, but the current evidence is scarce and contradictory. We assessed the link between knowledge of victimization and other relevant reporter characteristics in detecting and reporting children suspected to be victims of violence in a sample of 184 school staff members from Spain (84.02% females, M  = 43.40, SD  = 10.37). We compared participants who had never detected nor reported any cases (i.e., non-detectors) with participants who had detected but not reported outside school (i.e., inconsistent reporters) and participants who had detected and reported at least one potential case (i.e., consistent reporters). Knowledge about the reporting procedures varied significantly across groups. Years of experience was the only variable to significantly predict having detected at least one case across job experience. Knowing whether a report can be made anonymously or without the principal's consent was significant to predict the likelihood of being a consistent reporter, along with hours spent daily in contact with students. Trainings for school staff should be aware of what specific aspects of knowledge tend to increase detection and reporting. Interventions should include more specific guidelines and ways of recreating experience (e.g., role-playing, virtual scenarios) as an effective strategy to respond to cases of potential victimization encountered at school., Competing Interests: We confirm that this work is original and has not been published elsewhere, nor is it currently under consideration for publication elsewhere. We report no conflict of interest. We alone are responsible for the content and writing of the paper., (© 2020 Elsevier Ltd. All rights reserved.)

Vibrio natriegens is a naturally occurring marine bacterium that is emerging as a microbiological model system. Here, we describe Aquatic Killer 99 (AQKL99), a novel phage that infects Vibrio natriegens 14048. The genome of the phage is 58,464 bp long, has a GC content of 45.9%, and contains 51 protein-coding genes., (Copyright © 2020 Yonas et al.)

This article reviews the clinical features of systemic and autoimmune diseases affecting the perianal region and its surrounding integumentary structures.

Spiders (order Araneae, class Arachnida) are an important group of predatory arthropods in terrestrial ecosystems that have been recently identified as an untapped reservoir of single-stranded (ss)DNA viruses. Specifically, spiders harbour a diversity of ssDNA viruses encoding a replication-associated protein (Rep) within a circular genome. However, little is known about the ecology of novel circular Rep-encoding ssDNA (CRESS DNA) viruses. Here we investigated two CRESS DNA viruses recently identified in spinybacked orbweavers (Gasteracantha cancriformis), namely spinybacked orbweaver circular virus (SpOrbCV) 1 and 2. SpOrbCV-1 was detected in the majority (> 65 %) of spider specimens from all life stages, including eggs, spiderlings and adults, demonstrating that this virus is active within spinybacked orbweavers. In contrast, SpOrbCV-2 was only detected in adults at a lower (36 %) prevalence. Since we also detected SpOrbCV-2 in other spider species and this virus has been reported from a dragonfly, we suggest that SpOrbCV-2 is accumulated in these predators through common insect prey. The prevalence of SpOrbCV-1 in collected specimens allowed us to design assays to characterize this virus, which represents a new group of CRESS DNA viruses, the 'circularisviruses'. To our knowledge, SpOrbCV-1 is the first example of a vertically transmitted virus in spiders, which may explain its high prevalence in spinybacked orbweavers. Since vertically transmitted viruses infecting insects (class Insecta) can manipulate their host's behaviour and physiology, future studies should investigate the ecological role of vertically transmitted viruses in spiders.

Victimization has been widely demonstrated to have negative consequences in minors. Most crimes against children go unreported and victims tend to reach adulthood without receiving any of the available specialized support. Studies have highlighted the unique role of school workers in early detection and reporting of possible cases of victimization, and have also found high rates of underreporting by school staff. The present study analyzes the underreporting of child and youth victimization suspicions among school staff and aims to identify variables related to its detection and reporting. One hundred and eighty-four school staff members (83.7% females, M=42.6years old, SD=11.7) from 17 different schools completed a self-administered questionnaire designed to record their knowledge and experience regarding the detection and reporting of potential victimization cases. Over 74% of the school workers had suspected at least one situation of victimization during their careers, but only 27% had actually reported these concerns. Higher rates of reporting were significantly associated with male gender, more years of experience, and awareness of five common misconceptions. Reporting behavior could be predicted by gender, years of experience and two statements assessing respondents' knowledge of victimization. In order to increase early reporting of possible cases of victimization, it is necessary to overcome certain misconceptions, raise awareness among school staff, design new training programs or interventions, and adapt the school dynamics in the light of these findings., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Preventing HIV transmission by the use of a vaginal microbicide is a topic of considerable interest in the fight against AIDS. Both a potent anti-HIV agent and an efficient formulation are required to develop a successful microbicide. In this regard, molecules able to inhibit the HIV replication before the integration of the viral DNA into the genetic material of the host cells, such as entry inhibitors or reverse transcriptase inhibitors (RTIs), are ideal candidates for prevention purpose. Among RTIs, S- and N-dihydroalkyloxybenzyloxopyrimidines (S-DABOs and N-DABOs) are interesting compounds active at nanomolar concentration against wild type of RT and with a very interesting activity against RT mutations. Herein, novel N-DABOs were synthesized and tested as anti-HIV agents. Furthermore, their mode of binding was studied by molecular modeling. At the same time, a vaginal microbicide gel formulation was developed and tested for one of the most promising candidates.

As dominant members of marine mesozooplankton communities, copepods play critical roles in oceanic food webs and biogeochemical cycling. Despite the ecological significance of copepods, little is known regarding the causes of copepod mortality, and up to 35% of total copepod mortality cannot be accounted for by predation alone. Viruses have been established as ecologically important infectious agents in the oceans; however, viral infection has not been investigated in mesozooplankton communities. Here we used molecular and microscopic techniques to document viral infection in natural populations of the calanoid copepods Acartia tonsa (Dana) and Labidocera aestiva (Wheeler) in Tampa Bay, FL. Viral metagenomics revealed previously undocumented viruses in each species, named Acartia tonsa copepod circo-like virus (AtCopCV) and Labidocera aestiva copepod circo-like virus (LaCopCV). LaCopCV was found to be extremely prevalent and abundant in L. aestiva populations, with up to 100% prevalence in some samples and average viral loads of 1.13 × 10(5) copies per individual. LaCopCV transcription was also detected in the majority of L. aestiva individuals, indicating viral activity. AtCopCV was sporadically detected in A. tonsa populations year-round, suggesting temporal variability in viral infection dynamics. Finally, virus-like particles of unknown identity were observed in the connective tissues of A. tonsa and L. aestiva by transmission electron microscopy, demonstrating that viruses were actively proliferating in copepod connective tissue as opposed to infecting gut contents, parasites, or symbionts. Taken together, these results provide strong independent lines of evidence for active viral infection in dominant copepod species, indicating that viruses may significantly influence mesozooplankton ecology.

Despite many advances in antifungal drug development and therapy, onychomycosis due to nondermatophyte molds (NDM) remains difficult to treat. Using a reference microdilution method (CLSI M38-A), the antifungal susceptibility to bifonazole, ciclopiroxolamine, fenticonazole, itraconazole, ketoconazole, miconazole, terbinafine and tioconazole of 64 molds isolated from toenail onychomycosis was studied. All the strains showed good susceptibility to ciclopiroxolamine. Aspergillus had excellent susceptibility to itraconazole followed by miconazole, ketoconazole, tioconazole, fenticonazole and terbinafine. The isolated species had variable susceptibility to bifonazole. Scopulariopsis had wide MIC ranges for all antifungal drugs tested except ciclopiroxolamine. Fusarium and Acremonium had reduced susceptibility to antifungal drugs tested. Nevertheless, some strains show low MICs for ketoconazole, miconazole and tioconazole.Studies to evaluate in vitro susceptibility testing using CLSI methods for NDM onychomycosis should be undertaken.

The widespread use of sonography as a screening tool for fetal anomalies has facilitated prenatal detection of several fetal conditions characterized by urinary tract dilatation. These conditions are more common in male fetuses and are generally a result of an anatomic defect causing obstruction along the urinary tract system. Although the prognosis of these conditions largely depends on the specific anomaly, several poor prognostic factors have been described. These factors include detection at an early gestational age, bilateral marked dilatation, a persistently obstructed bladder, oligohydramnios causing pulmonary hypoplasia, and the presence of associated fetal or chromosomal anomalies. We report a case in which a male fetus at 14 weeks' gestation had a diagnosis of rapidly progressing bilateral hydronephrosis, massive bladder dilatation, hydroureter, and a surprisingly normal amniotic fluid volume. Serial sonographic surveillance assisted us in obtaining the correct diagnosis, which was important for adequately consulting the patient regarding the fetal prognosis in the affected index pregnancy as well as the likelihood of recurrence in future gestations.

Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors of the intestinal tract that typically occur in adults over the age of 40 years. GISTs in younger patients are rare and not well characterized. The objective was to define the characteristics of GISTs in children and young adults (<30 years old). Clinicopathologic and molecular features, including KIT/PDGFRA genotype, in GISTs from 5 children and 10 young adults were analyzed. Gene expression analysis was performed on 5 gastric tumor samples from 2 children, 2 gastric tumors from young adults, and 10 gastric GISTs from older adults using an U133A Affymetrix platform (22,000 genes). All five pediatric GISTs occurred in girls, involved the stomach as multiple nodules, showed predominantly an epithelioid morphology, often involved lymph nodes, and lacked KIT or PDGFRA mutations. Although all five patients developed recurrence (four in the liver, three in the peritoneum, and two in both sites), four are still alive with disease. Of the 10 GISTs in young adults, half occurred in the small bowel and had spindle cell morphology, and one case had lymph node metastasis. KIT mutations were identified in seven cases, four in exon 11 and three in exon 9. Seven patients developed recurrence, and at last follow-up two patients had died of disease. Gene expression analysis showed high expression of PHKA1, FZD2, NLGN4, IGF1R, and ANK3 in the pediatric and young adult versus older adult cases. GISTs that occur in children are a separate clinicopathologic and molecular subset with predilection for girls, multifocal gastric tumors, and wild-type KIT/PDGFRA genotype. In contrast, GISTs in young adults are a more heterogeneous group, including cases that resemble either the pediatric or the older adult-type tumors. The distinct gene expression profile suggests avenues for investigation of pathogenesis and potential therapeutic strategies.

We determined growth hormone (GH) and insulin-like growth factor I (IGF-I) levels after a 3 h infusion of escalating doses of growth hormone-releasing hormone (GHRH(1-29)) followed by a bolus injection in hypopituitary patients with marked differences in pituitary features at magnetic resonance imaging (MRI) in order to evaluate further the contribution of MRI in the definition of pituitary GH reserve in GH-deficient patients. Twenty-nine patients (mean age 14.5 +/- 4.0 years) were studied. Group I comprised 13 patients: seven with isolated GH deficiency (IGHD) (group Ia) and six with multiple pituitary hormone deficiency (MPHD) (group Ib) who had anterior pituitary hypoplasia, unidentified pituitary stalk and ectopic posterior pituitary at MRI, Group II consisted of eight patients with IGHD and small anterior pituitary/empty sella, while in group III eight had IGHD and normal morphology of the pituitary gland. Growth hormone and IGF-I levels were measured during saline infusion at 08.30-09.00 h, as well as after infusion of GHRH (1-29) at escalating doses for 3h: 0.2 micrograms/kg at 09.00-10.00 h, 0.4 micrograms/kg at 10.00-11.00 h, 0.6 micrograms/kg at 11.00-12.00 h and an intravenous bolus of 2 micrograms/ kg at 12.00 h. In the group I patients, the peak GH response to GHRH(1-29) was delayed (135-180 min) and extremely low (median 2mU/l). In group II it was delayed (135-180 min), high (median 34.8 mU/l) and persistent (median 37.4 mU/l at 185-210 min). In group III the peak response was high (median 30.8 mU/l) and relatively early (75-120 min) but it declined rapidly (median 14.4 mU/l at 185-210 min). In one group I patient, GH response increased to 34.6 mU/l. The mean basal value of IGF-I levels was significantly lower in group I (0.23 +/- 0.05 U/ml) than in groups II (0.39 +/- 0.13U/ ml, p < 0.01) and III (1.54 +/- 0.46 U/ml, p < 0.001) and did not vary significantly during the GHRH(1-29) infusion. The present study demonstrates that the impaired GH response to 3 h of continuous infusion of escalating doses of GHRH(1-29) was strikingly indicative for pituitary stalk abnormality, strengthening the case for use of GHRH in the differential diagnosis of GH deficiency. The low GH response, more severe in MPHD patients, might be dependent on the residual somatotrope cells, while the better response (34.6 mU/l) in the group Ia patients might suggest that prolonged GHRH infusion could help in evaluating the amount of residual GH pituitary tissue. Pituitary GH reserve, given the GH response to GHRH infusion in GH-deficient patients with small anterior pituitary/empty sella, seems to be maintained.

Rainbow trout (Oncorhynchus mykiss) were exposed to ion-poor (soft) water to test the hypothesis that naturally induced proliferation of branchial chloride cells causes a thickening of the blood-to-water diffusion barrier. This was achieved by using a combination of scanning and transmission electron-microscopic techniques. Fish were exposed to soft-water conditions ([Na+]= 0.055 mmol l-1, [Cl-] approximately 0.029 mmol 1(-1), [Ca2+] approximately 0.059 mmol 1(-1), and [K+] approximately 0.007 mmol 1(-1)) for 1, 2, and 4 weeks. Marked chloride cell proliferation was evident at all sampling times with an approximate doubling of the gill epithelial surface area covered by chloride cells exposed to the water ("chloride cell fractional area"). The increases in chloride cell fractional area resulted from both increased numbers of cells and expanded apical surfaces of exposed individual cells. As a result of chloride cell proliferation, soft-water exposure was associated with a doubling of the lamellar blood-to-water diffusion distance from 3.26+/-0.08 microM to 6.58+/-0.43 microM as determined from transmission electron micrographs. These data demonstrated a positive correlation between chloride cell fractional area and blood-to-water diffusion distance. We conclude that, in trout, chloride cell proliferation during soft-water exposure, while presumably benefiting ionic regulation, may impair gas transfer owing to the associated thickening of the blood-to-water diffusion barrier.

Data on circadian rhythms of serum lipids and apolipoproteins in animals and in human subjects are scarce. The goal of this study was to investigate the existence of circadian rhythms in the lipids and apolipoproteins of fasted rats. We showed that in fasted rats well-defined circadian rhythms were present in total serum triglycerides and in cholesterol and triglycerides of very low density lipoprotein (VLDL), intermediate density lipoprotein-low density lipoprotein (IDL-LDL) and high density lipoprotein (HDL). Moreover, our data clearly show that the circadian rhythm of lipoproteins is accompanied by a well defined circadian rhythm of B apoprotein, in all lipoprotein classes examined.

Circadian rhythms of hypothalamic catecholamines and their metabolites and of prolactin and corticosterone circulating hormones were determined over 24 h in group-housed (six per cage; control) and individually housed, 90-day-old male albino rats adapted to a 12:12 light/dark cycle. After 5 weeks of adaptation, in individually housed rats, norepinephrine (NE) turnover increased, since lower NE (p < 0.01) and higher MOPEG metabolite (p < 0.01) levels were measured. As concerns the dopaminergic system, individually housed rats increased both dopamine (DA) synthesis and turnover as revealed by higher DOPAC (p < 0.01) and HVA (p < 0.05) metabolites without modification of DA levels. Moreover, in individually housed rats, corticosterone (p < 0.01) and prolactin (p < 0.05) mean levels were higher than in the control group.

The branchial Ca(2+) uptake by teleost fish is under inhibitory control by the hormone stanniocalcin (STC) which is generated by the corpuscles of Stannius (CS). Removal of the CS in North American eel, Anguilla rostrata LeSueur, induced a rapid rise in blood calcium levels. Branchial Ca(2+) influx following the extirpation of the CS (stanniectomy, STX) increased during the first four days and stayed elevated thereafter (in agreement with previous studies). The transepithelial potential (TEP) across the gills did not change after STX and this means that the electrochemical gradient for Ca(2+) is less favourable for passive influx of Ca(2+) in STX eel. Therefore, the Ca(2+) influx in STX eels is a transcellular flux, with Ca(2+) crossing the apical and basolateral membrane barrier. The kinetics of ATP-driven Ca(2+)-transport across basolateral plasma membranes from eel gills did not change after STX. Thus, the increased Ca(2+)-influx after STX is not correlated with changes in ATP-dependent Ca(2+)-extrusion across the basolateral membrane, suggesting a regulation at the apical membrane. Moreover, STC did not affect ATP-driven Ca(2+)-transport in isolated basolateral membranes (in vitro). STC (0.1 nM) reduced cAMP levels in dispersed eel gill cells. It had no significant effect on the IP3 levels in these cells. We postulate that STC controls the permeability to Ca(2+) of the apical membranes of the Ca(2+) transporting cells of fish gills by controlling second messenger operated Ca(2+) channels in the apical membrane.

The circadian rhythms of hypothalamic norepinephrine (NE) and of circulating norepinephrine, epinephrine (E), corticosterone, aldosterone, and serotonin (5HT) were determined in group-housed and in individually housed male adult rats, adapted to a 12/12 light/dark cycle. After 5 weeks of individual housing, compared to group-housed animals, hypothalamic NE mesor decreased, while circulating NE, E, and corticosterone mesor increased. The circadian rhythms of aldosterone and 5HT were unaffected by individual housing.

The circadian rhythms of hypothalamic serotonin (5HT), tryptophan (TP) and 5-hydroxy-indoleacetic acid (5HIAA), and serum corticosterone were determined in male Wistar rats. The animals underwent a five-week 12:12-hr light/dark cycle conditioning period and were divided into three groups: rats housed four to a cage (group C, control), rats housed individually (group I), and rats housed individually and treated for two weeks with 10 mg/kg/day of imipramine continuously administered by osmotic pumps implanted under the skin (group T). Significant differences were found in the acrophases of 5HT, TP and 5HIAA between group I and group C, and corticosterone mesor was higher in group I than in group C. On the contrary, no differences were observed between group T (individually housed, but given imipramine) and group C. Therefore, chronically administered imipramine antagonizes the circadian changes induced by individual housing.

Hypothalamic tryptophan (TP), serotonin (5HT) and 5-hydroxy-indoleacetic acid (5HIAA), serum tryptophan (free and total), and circulating corticosterone and aldosterone were measured over 24 hr in 60-day-old male rats fed high (60%) and low (6%) protein diets. The diets were administered during specific stages of rat growth: fetal phase and suckling (when the process of mitosis is most rapid), post-lactation, and from the fetal phase through to the adult stage. In all groups, there was a direct correlation between protein intake and hypothalamic and serum TP levels. Remarkable decreases in the amplitude and mesor of the aldosterone rhythm were observed when the hyperprotein diet was administered in the fetal and suckling phases, or from the fetal phase until the adult stages. The rhythm of the serotonin system was significantly altered by a low protein diet: decreased 5-HT amplitude (low protein diet in the fetal stage and suckling), decreased 5-HT amplitude and deranged 5-HIAA rhythm (low protein in the post-lactation period), deranged 5-HIAA rhythm (low protein diet throughout the experiment). Lastly, there was a remarkable increase in the corticosterone mesor in rats administered a low protein diet after weaning and in rats constantly given this diet. Growth was greatly inhibited in these two groups of animals, therefore, it cannot be excluded that the high levels of circulating hormone resulted from their debilitated condition.

The possible interrelations between ascorbic acid, cholesterol and plasma triglycerides were studied in the residents of an old people's home. The study lasted about five months, from autumn to spring, and concerned 100 people in good health, both males and females, whose age varied from 70 to 84. Old people's diets proved well balanced and varied to such an extent as to supply them with a satisfying amount of calories and vitamin C. The results of this study showed that the average plasma levels of ascorbic acid [1] approached the lower level of normal values (587 +/- 34 micrograms %), [2] depended on sex (in fact it was significantly lower in males) (p less than 0.01), and [3] depended on diets which varied according to the different seasons when drawings were made (p less than 0.01). Moreover, in all cases there was a significantly negative correlation between ascorbic acid and cholesterol (p less than 0.05), whereas no significant correlation seemed to exist between ascorbic acid and triglycerides. On the contrary, a significant positive correlation between cholesterol and triglycerides was observed (p less than 0.01). The above-mentioned correlations seem to be valid only for males. This study confirmed by partial 3 variant correlations, produced results that point out the risk of hypercholesterolemia connected with chronic hypovitaminosis C, a characteristic feature of old age.

The effects of a high protein diet (casein 40%, lactalbumin 20%) were evaluated in pregnant and/or suckling rats. Histological studies of the organs showed structural alterations to the liver, adrenal cortex, kidneys and heart accompanied by significant metabolic changes in blood glucose and triglyceride levels. Overall the experimental results encourage the belief excessive intake of animal protein, particularly at an early stage, may do specific damage to the normal course of pregnancies, given the low birth rate and high incidence of perinatal mortality observed in the offspring produced by mothers given high protein diets throughout pregnancy.

The hematic level of ascorbic acid was significantly lower with respect to that of healthy subjects in 55 patients with hemorrhagic ocular diseases. Experiments on albino guinea pigs showed that an induced hypovitaminosis C (2 weeks of scorbutigenic diet followed by a maintenance dose of 0,5 mg of ascorbic acid) caused the appearance of widespread retina hemorrhages and a significant decrease of the blood ascorbate levels with respect to the control groups. The present results suggest that a prolonged insufficient dietary intake of ascorbic acid may give rise to hemorrhagic ocular pathologies in humans.

Pregnant rats, Wistar strain, were treated from day 11 of gestation with synthetic diets containing different amounts of protein. The Group of rats fed a severely deficient protein diet (4% of casein, 2% of lactalbumin) showed reduced hematocrit, hemoglobin, total protein and an expressive increase of gamma globulins compared with rats treated with normal or elevated protein levels. Weight gain during pregnancy was higher for rats which received a larger amount of protein; on the contrary those that were subjected to malnutrition had no weight gain and bore prematurely with high percent of foetal mortality.