Suicidal ideation and self-harm behavior in a community sample of preadolescent youth: a case-control study

ObjectiveResearch has focused on understanding risk factors associated with suicidal ideation and self-harm behaviors in older youth, but less is known regarding these behaviors in preadolescents. We examined characteristics associated with suicidal ideation and self-harm behavior in youth aged 10–13 years.Design/MethodsA community sample of 387 youth was enrolled in a prospective study assessing precursors of risk behaviors. Twenty-three subjects endorsing items regarding suicidal ideation or self-harm behaviors (Achenbach's Youth Self-Report) (endorsers) were matched with 23 non-endorsers. Groups were compared on problem behaviors, impulsivity, neurocognitive function, risk behaviors, and other variables.ResultsEndorsers had higher levels of impulsivity, were more likely in borderline/clinical range on 5 of 8 Youth Self-Report Syndrome scales, and reported more risk taking. Endorsers and non-endorsers were similar in neurocognitive function. More non-endorsers were on stimulants, but groups were similar in parental monitoring and parental report of behavioral/emotional issues, socioeconomic status, and marital status.ConclusionIn this study, preadolescent endorsers report significantly more problem behaviors than non-endorsers. However, parental monitoring and parent report of problems were similar between groups. Given these findings, we suggest that at-risk youth may be underrecognized at young ages.     

Male hypogonadism

The hypothalamic–pituitary–gonadal (HPG) axis regulates the development, endocrine and reproductive function of the gonads throughout all phases of life. Male hypogonadism is defined an inadequate gonadal function, as manifested by deficiency in gametogenesis and/or secretion of gonadal hormones. In most cases, male hypogonadism is diagnosed through detailed history, physical examination and a few basic hormonal evaluations. In selected cases, however, additional tests are needed to define the aetiology and the extent of HPG axis dysfunction. These include semen analysis, pituitary imaging studies, genetic studies, bone densitometry, testicular ultrasonography, testicular biopsy and hormonal dynamic testing. The stimulation tests of the HPG are of particular importance in the differential diagnosis of congenital delayed puberty versus pre-pubertal hypogonadism in children. This review will focus on the methods, indications and limitations of endocrine testing in the characterisation and differential diagnosis of male hypogonadism at various ages. A practical hands-on guide on how to perform these tests is also provided.     

Pooled Analysis of Clinical Outcome of Patients with Chemorefractory Metastatic Colorectal Cancer Treated within Phase I/II Clinical Studies Based on Individual Biomarkers of Susceptibility: A Single-Institution Experience

Background

Patients with metastatic colorectal cancer (mCRC) refractory to standard therapies have a poor prognosis. In this setting, recruitment into clinical trials is warranted, and studies driven by selection according to individual tumor molecular characteristics are expected to provide added value.

Objective

We retrospectively analyzed data from patients with mCRC refractory to or following failure of standard therapies who were enrolled into phase I/II clinical studies at the Niguarda Cancer Center based on the presence of a specific molecular profile expected to represent the target of susceptibility to the experimental drug(s).

Patients and Methods

From June 2011 to May 2016, 2044 patients with mCRC underwent molecular screening. Eighty patients (3.9%) were enrolled in ad hoc studies; the median age was 60 years (range 36–86) and the median number of previous treatment lines was five (range 2–8). Molecular characteristics exploited within these studies were MGMT promoter hypermethylation (48.7%), HER2 amplification (28.8%), BRAF ^V600E mutation (20%), and novel gene fusions involving ALK or NTRK (2.5%).

Results

One patient (1%) had RECIST (Response Evaluation Criteria In Solid Tumors) complete response (CR), 13 patients (16.5%) experienced a partial response (PR), and 28 (35%) stable disease (SD). Median progression-free survival (PFS) was 2.8 months (range 2.63–3.83), with 24% of patients displaying PFS >5 months. Median growth modulation index (GMI) was 0.85 (range 0–15.61) and 32.5% of patients had GMI >1.33. KRAS exon 2 mutations were found in 38.5% of patients, and among the 78 patients with known KRAS status, those with wild-type tumors had longer PFS than those with mutated tumors (3.80 [95% CI 2.80–5.03] vs. 2.13 months [95% CI 1.77–2.87], respectively, p = 0.001). Median overall survival (OS) was 7.83 months (range 7.17–9.33) for all patients, and patients with KRAS wild-type tumors had longer OS than those with mutated tumors (7.83 [95% CI 7.33–10.80] vs. 7.18 months [95% CI 5.63–9.33], respectively, p = 0.06).

Conclusions

This single-institution retrospective study indicates that in a heavily pretreated population approximately 4% of mCRC tumors display a potential actionable molecular context suitable for therapeutic intervention. Application of molecular selection is challenging but improves clinical outcome even in later lines of treatment.

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Gambling initiation in preadolescents

Gambling has increased in the past decade, with growing opportunities for initiation by adolescents. More limited data, however, are available regarding gambling in preadolescents. In the investigation reported here, gambling for money was the most common risk behavior in 10- to 12-year-olds. Gamblers were more likely to be white, have tried alcohol, have positive affect toward gambling, and have friends who gamble.     

From microbiota toward gastro-enteropancreatic neuroendocrine neoplasms: Are we on the highway to hell?

Gut microbiota is represented by different microorganisms that colonize the intestinal tract, mostly the large intestine, such as bacteria, fungi, archaea and viruses. The gut microbial balance has a key role in several functions. It modulates the host’s metabolism, maintains the gut barrier integrity, participates in the xenobiotics and drug metabolism, and acts as protection against gastro-intestinal pathogens through the host’s immune system modulation. The impaired gut microbiota, called dysbiosis, may be the result of an imbalance in this equilibrium and is linked with different diseases, including cancer. While most of the studies have focused on the association between microbiota and gastrointestinal adenocarcinomas, very little is known about gastroenteropancreatic (GEP) neuroendocrine neoplasms (NENs). In this review, we provide an overview concerning the complex interplay between gut microbiota and GEP NENs, focusing on the potential role in tumorigenesis and progression in these tumors.

     

Effect of hindlimb immobilization upon skeleton muscle calcium in rat

A state of disuse was produced in skeletal muscle by immobilizing both hindlimbs of the rat with plaster of paris. After 4 weeks of immobilization, the calcium concentration increased in the three different fiber types of the immobilized hindlimb. The non-immobilized muscle of a rat showed no significant increase in calcium concentration when other limbs of the same rat were fixed immobile. The percentage increase in calcium within skeletal muscle after immobilization may be related to the absolute reduction in muscular activity from control levels

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Zusammenfassung Durch die Immobilisierung beider Hinterbeine der Ratte mittels Gips wurde in den Skeletmuskeln ein Zustand der Verkümmerung hervorgerufen. Nach 4wöchiger Immobilisierung nahm die Calciumkonzentration in den drei verschiedenen Fasertypen des immobilisierten Hinterbeines zu. Der nicht-immobilisierte Muskel einer Ratte zeigte keine bedeutende Zunahme der Calciumkonzentration, wenn andere Glieder derselben Ratte stillgelegt wurden. Die prozentuale Zunahme an Calcium im Skeletmuskel nach der, Immobilisierung kann mit der absoluten Herabsetzung der Muskeltätigkeit im Vergleich mit Kontrollen in Zusammenhang gebracht werden.

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Résumé Un état pathologique est produit au niveau des muscles squelettiques en immobilisant l'arrière-train de rats à l'aide de plâtre de Paris. Après 4 semaines d'immobilisation, la concentration en calcium augmente au niveau des trois types de fibres des parties immobilisées. Le muscle non immobilisé d'un rat en présente pas d'augmentation significative de la concentration en calcium, lorsque d'autres membres du même rat sont immobilisés. Le pourcentage d'augmentation du calcium dans les muscles squelettiques, après immobilisation, pourrait être en rapport avec la diminution absolue d'activité musculaire par rapport aux témoins.

     

Childhood poverty: specific associations with neurocognitive development

Growing up in poverty is associated with reduced cognitive achievement as measured by standardized intelligence tests, but little is known about the underlying neurocognitive systems responsible for this effect. We administered a battery of tasks designed to tax-specific neurocognitive systems to healthy low and middle SES children screened for medical history and matched for age, gender and ethnicity. Higher SES was associated with better performance on the tasks, as expected, but the SES disparity was significantly nonuniform across neurocognitive systems. Pronounced differences were found in Left perisylvian/Language and Medial temporal/Memory systems, along with significant differences in Lateral/Prefrontal/Working memory and Anterior cingulate/Cognitive control and smaller, nonsignificant differences in Occipitotemporal/Pattern vision and Parietal/Spatial cognition.