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Burkitt lymphoma (BL) is a rare and highly aggressive subtype of non-Hodgkin’s lymphoma. Several studies have identified prognostic factors (PFs) for disease progression and mortality among adults with BL. However, there is no consensus on risk stratification based on PFs. This study aims to identify, critically assess, and synthesize the available evidence on PFs for survival in adults with BL.
Methods
A systematic review of the literature was conducted. MEDLINE, Embase, and CENTRAL were searched from inception to 22 February 2022. Randomized or non-randomized clinical trials and longitudinal observational studies were eligible for inclusion. Reference screening, data extraction, and risk-of-bias assessment using the Quality in Prognosis Studies (QUIPS) tool for prognostic factor studies were conducted independently and in duplicate. Publication bias was examined by visual inspection of funnel plots. Effect measures and the corresponding 95% confidence intervals were pooled with an indirect variance estimation in meta-analyses using Review Manager 5, and sensitivity analyses were conducted. Certainty of evidence was assessed using GRADE.
Results
The search identified 1,119 references after duplicate removal. Of these, 76 potentially relevant papers were selected for full-text assessment and 36 studies (N=10,882) reported in 39 articles were eligible for inclusion. Older age, higher performance status, and central nervous system involvement were associated with poorer overall survival (OS) and progression-free survival (PFS). Black patients exhibited significantly lower OS and relative survival. Bone marrow involvement and higher albumin levels were associated with poorer OS. Treatment with rituximab and treatment with methotrexate were associated with better OS and PFS. No significant differences in survival were found for HIV status, sex, and risk stratification.
Conclusions
This study, framed within a collaboration with European Reference Network EuroBloodNet, provides a comprehensive and methodologically rigorous evidence review on PFs in adults with BL. Several significant associations of PFs and survival estimates were observed, providing data to inform treatment decisions and to improve patient care.
Patients with schizophrenia die decades earlier than the general population. Among the factors involved in this mortality gap, evidence suggests a telomere length shortening in this clinical population, which is associated with premature ageing. Recent studies support the use of strength-based training exercise programmes to maintain, or even elongate, telomere length in healthy elderly populations. However, studies aiming at modifying telomere length in severe mental illnesses, such as schizophrenia, are still very scarce.
Aims
To investigate the effect of a strength-based physical exercise programme on the telomere length of individuals with schizophrenia.
Method
We propose a pragmatic, randomised controlled trial including 40 patients aged ≥18 years, with a stable diagnosis of schizophrenia, attending the Complejo de Rehabilitación Psicosocial (CRPS, Psychosocial Rehabilitation Centre) in Salamanca, Spain. These patients will be randomly assigned (1:1) to either receive the usual treatment and rehabilitation programmes offered by CRPS (treatment-as-usual group) or these plus twice weekly sessions of an evidence-based, strength-based training exercise programme for 12 weeks (intervention group). The primary outcome will be effect on telomere length. Secondary outcomes will include impact on cognitive function, frailty and quality of life.
Results
We expect to show the importance of implementing strength-based physical exercise programmes for patients with schizophrenia. We could find that such programmes induce biological and genetic changes that may lengthen life expectancy and decrease physical fragility.
Conclusions
We anticipate that our trial findings could contribute to parity of esteem for mental health, reducing premature ageing in patients with severe mental illnesses, such as schizophrenia.
The World Health Organization and the Global Burden of Disease study estimate that almost 800 000 people die from suicide yearly. The role of non-traditional risk factors such as climate and high-altitude exposure are poorly understood.
Aims
This study aims to determine a potential relationship between altitude exposure and suicide rates among 221 cantons located at different altitudes ranging from 0 to 4300 m.
Method
We conducted an 11-year, country-wide, population-based analysis on age- and gender-standardised suicide rates in Ecuador, based on the official data from the National Institute of Statistics, using all available self-harm death codes (ICD-10 codes X60–X84).
Results
A total of 11 280 cases of suicide were reported during 2011–2021. Suicide rates were higher among men (11.48/100 000). In terms of elevation, suicide rates were significantly higher among people from high-altitude cantons (3.7/100 000) versus those from low-altitude cantons. When applying the International Society Mountain Medicine categorisation, suicide rates were significantly higher at moderate- (4.3/100 000), high- (3.6/100 000) and very-high-altitude cantons (4.4/100 000) when compared with low-altitude locations (2.5/100 000).
Conclusions
Ecuador is one of the few countries that has a vast range of cantons located at different altitudes. We found that living at higher elevations is positively associated with greater suicide rates. Although the rates are significantly greater as elevation increases, a clear linear relationship is not apparent, likely because of the interplay of socioeconomic factors, including urbanicity. The effect of chronic hypobaric hypoxia on mood cannot be ruled out, although the existence of causal mechanisms remains to be elucidated.
Prior literature has documented how motives for cannabis use predict frequency of use and cannabis use problems among adolescents. However, few studies have examined possible moderating variables that may influence the association between cannabis use motives and frequency of use. The current study examines how risky decision-making moderates this association to help better understand which individuals are at greater risk for cannabis use escalation. The current study will be the first to examine the interactive effects of motives for cannabis use (i.e., health or recreational reasons) and risky decision-making on cannabis use trajectories among a sample of adolescent cannabis users.
Participants and Methods:
Data from 194 adolescent cannabis users aged 14–17 at baseline were analyzed as part of a larger longitudinal study. Participants included those who self-reported use of cannabis within six months prior to the baseline assessment. The Marijuana Reasons for Use Questionnaire (MJRUQ) was used to assess motives for cannabis use from a list of 13 items. A confirmatory factor analysis identified “health” and “recreational” factors for motives for cannabis use. Lifetime frequency of cannabis use (number of days used) was assessed through the Drug Use History Questionnaire, while risky decision-making was assessed using the Game of Dice Task. We used latent growth curve modeling and linear regression analyses to examine the interactive effects of motives for cannabis use and risky decision-making on initial levels of lifetime cannabis use at baseline, and rate of cannabis use escalation over time.
Results:
No significant interactive effects were found for health motives for cannabis use; however, we found significant main effects of health motives on initial levels of lifetime cannabis use at baseline (b = 100.82, p < .01) and rate of cannabis use escalation (b = 24.79, p < .01). Those with a greater proclivity to use cannabis for health purposes showed higher initial levels of lifetime use at baseline and steeper increases in the rate of cannabis use escalation relative to those less likely to use for health purposes. Furthermore, we found a significant interactive effect of recreational motives for use and risky decision-making on the rate of cannabis use escalation (b = -2.53, p < .01). Follow-up analyses revealed that among those less likely to use cannabis for recreational purposes, higher risky decision-making was associated with a steeper increase in the rate of cannabis use escalation relative to those who exhibited lower risky decision-making.
Conclusions:
The current study replicated findings suggesting that cannabis use motives influence cannabis use trajectories. We found that using cannabis primarily for health reasons was associated with higher initial levels and steeper increases in use regardless of decision-making. Furthermore, we found that both motives for use and risky decision-making interacted to influence associations with cannabis use trajectories. Specifically, among individuals reporting less cannabis use for recreational reasons, those with relatively riskier decision-making showed steeper increases in the rate of cannabis use escalation. These findings inform prevention and intervention practices that focus on decision-making by tailoring approaches based on an individual’s primary motives for cannabis use.
A recent review called for a more robust assessment of cannabis use (CU), including amount and timing of recent use to assess neurocognitive effects of CU among people living with HIV (PWH) (Ellis et al., 2021). The current study addresses some issues raised by investigating between group neurocognitive differences among healthy controls and PWH who differ on their cannabis use histories, using strict inclusion criteria, robust classification of CU, and administration of an established neurocognitive test battery.
Participants and Methods:
Among this community sample of adults (N=309), 58 were classified as CU+/HIV+ group (84.5% Male), 76 as CU-/HIV+ (57.9% M), 86 as CU+/HIV- (58.1% M), and 89 as CU-/HIV- (53.9% M). Exclusion criteria included history of past 12-month dependence and extensive lifetime dependence or significant use of illicit substances other than cannabis, severe or current mood or thought disorder, and other medical conditions that adversely impact neurocognitive functioning. Inclusion criteria for CU+ groups included <30-days since last CU, >10 times of CU in last month, 3 times of CU per month in last 12 months, > 1 year of CU, and > 500 times used in lifetime. CU parameters did not statistically differ between HIV+/CU+ and HIV-/CU+. CU- groups’ inclusion criteria required no CU in last 6 months, 196 lifetime number of times used, and no history of CU dependance. Lifetime CU did not statistically differ between CU-/HIV+ and CU-/HIV- groups. HIV+ groups did not differ significantly on HIV viral load in plasma or nadir CD4+ counts. Significant between group differences included age, sex, years of education, and amount of alcohol and nicotine use within 12 months. The aforementioned sociodemographic and substance use variables that differed between groups were covariates in analyses. A battery of 10 neurocognitive measures, two measures per each domain of learning, memory, motor, executive functioning, and processing speed. Global composite summary scores for overall neurocognitive performance were calculated by averaging M T-scores for each neurocognitive domain. Data transformations were used to address any violations of statistical assumptions.
Results:
To facilitate data reduction, neurocognitive task scores were standardized to T-scores using the M and SD of the CU-/HIV-group. An omnibus model of between-group comparisons on global neurocognitive task performance revealed no significant differences, F(3) = .16, p = .923. Subsequent Tukey’s post hoc test revealed no significant differences among the four groups. Results also revealed nonsignificant differences between groups in neurocognitive performance within each domain. However, the CU-/HIV- group performed significantly worse than the CU-/HIV+ group on the Executive Functioning domain, based on Tukey’s post hoc test.
Conclusions:
We found no significant global neurocognitive differences among groups; however, there was some evidence for domain-specific neurocognitive differences in executive functioning. This contrasts somewhat with existing literature on HIV and cannabis-associated neurocognitive deficits. Several factors may have contributed to this, including our relatively healthy PWH sample. Future analyses will examine interactive effects of HIV severity and severity of CU on neurocognition. This analysis will better determine who, among PWH, are most at-risk for cannabis-associated neurocognitive effects and what factors may exacerbate them.
The global market for biologics and biosimilar pharmaceutical products is experiencing rapid expansion, primarily driven by the continuous discovery of new molecules. However, information regarding Latin America’s biological market remains limited.
Cannabis use has been linked to poorer episodic memory. However, little is known about whether depression and sex may interact as potential moderators of this association, particularly among adolescents. The current study addresses this by examining interactions between depression symptoms and sex on the association between cannabis use and episodic memory in a large sample of adolescents.
Method:
Cross-sectional data from 360 adolescents (Mage = 17.38, SD = .75) were analyzed at the final assessment wave of a two-year longitudinal study. We used the Drug Use History Questionnaire to assess for lifetime cannabis use, and the Computerized Diagnostic Interview Schedule for Children, Fourth edition to assess the number of depression symptoms in the past year. Subtests from the Wechsler Memory Scale, Fourth Edition and the California Verbal Learning Test, Second Edition were used to assess episodic memory performance.
Results:
The effect of the three-way interaction among cannabis use, depression symptoms, and sex did not have a significant impact on episodic memory performance. However, follow-up analyses revealed a significant effect of the two-way interaction of cannabis use and depression symptoms on episodic memory, such that associations between cannabis use and episodic memory were only significant at lower and average levels of depression symptoms.
Conclusions:
Contrary to our hypotheses, we found that as depression symptoms increased, the negative association between cannabis use and episodic memory diminished. Given the use of a predominantly subsyndromic sample, future studies should attempt to replicate findings among individuals with more severe depression.
Following the previous patristic tradition, the Hispano-Christian authors oriented the historical interpretation as an essential element in the anti- Jewish discourse around the concept of the Salvation History. With the coming of the Christ, the Jews are ‘evicted’ from History in favour of the Verus Israel . The Augustinian theory of the ‘witness people’ would be assumed with probative value within providentialist history to the detriment of the ancient ‘chosen people’. Subjected by divine design to Christian political power, the Jews suffer the deserved punishment for their innumerable sins. The inheritance of this stigma and the inveterate Jewish unbelief will arouse divine reprobation while allowing the Gentile people, guided by the light of the Christ, to be uniquely incorporated into the Salvation History.
Keywords: Late Antiquity, Hispano-Christian authors, History of Salvation, Anti-Jewish polemics.
Devoto pueblo cristiano,
este misterio notad:
cómo el gran Vespasiano
siendo emperador romano
tuvo grave enfermedad,
que jamás salud halló
en los sus dioses vacíos
hasta que Dios lo sanó,
cuya muerte prometió
de vengarla en los judíos.
Y salió con grade armada
y militar aparato,
y por él fue derribada
Jerusalén y asolada
la sinagoga y Pilato.
Aucto de la destruición de Jerusalén
(finales del siglo XV), versos 1-15.
Introducción: la herencia escrituaria
Uno de los principios ideológicos que la clase intelectual pagana reprochaba al ‘naciente’ cristianismo era la ‘novedad’, su falta de antigüedad y de una tradición suficientemente consolidada que avalase su doctrina. Por ello, a sus ojos, carecía por completo de legítima autoridad. Los defensores a ultranza de las ancestrales creencias arraigadas en el mundo grecorromano recelaban de las nuevas formas de culto religioso por considerar que en su seno escondían la expresión de dañinas supersticiones. De ahí que los apologistas se apresuraran a presentar como propios los sagrados escritos de la tradición judía, asegurando que existía una estrecha vinculación entre los antiguos profetas y la doctrina cristológica que fundamentaba la creencia cristiana. La literatura bíblica proporcionaba así a los cristianos una respetable antigüedad, mayor incluso de la que gozaban los propios mitos grecorromanos. La Biblia se convirtió, de hecho, en la depositaria de la ‘verdad histórica’, si bien el sentido de muchos de sus libros no parecía del todo claro.
Reduced motivation is often noted as a consequence of cannabis use. However, previous work has yielded mixed results and focused largely on adults. To address these limitations, this study examined longitudinal associations between cannabis use and self-reported motivation in a large adolescent sample.
Method:
Participants were 401 adolescents aged 14–17 at baseline who completed five bi-annual assessments. We assessed motivation at three timepoints using two self-report questionnaires: the Apathy Evaluation Scale and the Motivation and Engagement Scale (disengagement, persistence, planning, self-efficacy, and valuing school subscales). Controlling for relevant covariates, we used latent growth curve modeling to characterize patterns of cannabis use and motivation over time, examining bidirectional influences between these processes.
Results:
On average, adolescent cannabis use frequency increased significantly over time. The disengagement and planning facets of motivation also increased significantly over time, whereas other aspects of motivation remained stable. At baseline, greater cannabis use was associated with greater disengagement, lower planning, and lower valuing of school. Greater baseline cannabis use also predicted lesser increases in disengagement over time. After controlling for the effect of sex, age, depression, and use of alcohol and nicotine, only the baseline association between cannabis use and valuing school remained significant.
Conclusions:
Our results do not support a prospective link between cannabis use and reduced motivation among adolescents. Although most observed associations were accounted for by covariates, greater cannabis use was cross-sectionally associated with lower perceived value of school, which may contribute to poorer educational and later life outcomes.
Prior research has shown that sipping of alcohol begins to emerge during childhood and is potentially etiologically significant for later substance use problems. Using a large, community sample of 9- and 10-year-olds (N = 11,872; 53% female), we examined individual differences in precocious alcohol use in the form of alcohol sipping. We focused explicitly on features that are robust and well-demonstrated correlates of, and antecedents to, alcohol excess and related problems later in the lifespan, including youth- and parent-reported externalizing traits (i.e., impulsivity, behavioral inhibition and activation) and psychopathology. Seventeen percent of the sample reported sipping alcohol outside of a religiously sanctioned activity by age 9 or 10. Several aspects of psychopathology and personality emerged as small but reliable correlates of sipping. Nonreligious sipping was related to youth-reported impulsigenic traits, aspects of behavioral activation, prodromal psychotic-like symptoms, and mood disorder diagnoses, as well as parent-reported externalizing disorder diagnoses. Religious sipping was unexpectedly associated with certain aspects of impulsivity. Together, our findings point to the potential importance of impulsivity and other transdiagnostic indicators of psychopathology (e.g., emotion dysregulation, novelty seeking) in the earliest forms of drinking behavior.
In recent years, research has been focusing on strategies to counteract inflammatory processes and age-related diseases(1). During ageing, a low-grade systemic inflammation is often associated to an altered intestinal permeability (IP) a condition that has been shown to promote inflammation possibly through the translocation of dietary and bacterial factors into the blood stream that activates the immune system(2).In this regard, dietary pattern and environmental factors could play a fundamental role because of their potential ability to modulate inflammation, IP and the gut microbial ecosystem (GME). Moreover, it has been hypothesized that bioactive compounds such as polyphenols may affect IP and GME(3).The MaPLE project (Microbiome mAnipulation through Polyphenols for managing gut Leakiness in the Elderly) aimed to investigate the hypothesis that a polyphenol-rich diet can improve IP condition in a target population with beneficial changes at intestine and systemic level. To this aim, a randomised, controlled, cross-over dietary intervention study (8-week polyphenol-rich diet versus 8-week control diet, separated by a wash-out period) was carried out in a group of older subjects (> 60 years) living in a well-controlled setting (i.e. nursing home). Markers related with IP, inflammation, oxidative stress, vascular function and intestinal microbial ecosystem were investigated in serum, urine and/or fecal samples. Moreover, blood bacteria DNAemia, and serum/urine metabolomics has been assessed. Moreover, a consistent nutritional evaluation of the standard menu (provided by the nursing home) and of weighed food diaries was performed, providing also data on actual polyphenol intake during the intervention. The results show there were higher levels of IP in the older subjects, and that the polyphenol-enriched diet changed the levels of serum zonulin, a marker of IP. In addition, an association between zonulin and blood bacterial load was demonstrated. Ongoing in vitro and in vivo experiments are exploring the potential effects of different polyphenols on IP and the mechanisms involved. The MaPLE project will generate new data to improve the understanding on the role of polyphenols in the modulation of intestinal microbiome and its interactions with the host.
Objective: Relative to the vast literature that employs measures of decision-making (DM), rigorous examination of their psychometric properties is sparse. This study aimed to determine whether three measures of DM assess the same construct, and to measure invariance of this construct across relevant covariates. Method: Participants were 372 adolescents at risk of escalation in cannabis use. DM was assessed via four indices from the Cups Task, Game of Dice Task (GDT), and Iowa Gambling Task (IGT). We used confirmatory factor analysis to assess unidimensionality of the DM construct, and moderated nonlinear factor analysis (MNLFA) to examine its measurement invariance. Results: The unidimensional model of DM demonstrated good fit. MNLFA results revealed that sex influenced mean DM scores, such that boys had lower risk-taking behaviors. There was evidence of differential item functioning (DIF), such that IQ and age moderated the IGT intercept and GDT factor loading, respectively. Significant effects were retained in the final model, which produced participant-specific DM factor scores. These scores showed moderate stability over time. Conclusions: Indices from three DM tasks loaded significantly onto a single factor, suggesting that these DM tasks assess a single underlying construct. We suggest that this construct represents the ability to make optimal choices that maximize rewards in the presence of risk. Our final DM factor accounts for DIF caused by covariates, making it comparable across adolescents with different characteristics. (JINS, 2019, 25, 661–667)
Callous-unemotional (CU) traits are critical to developmental, diagnostic, and clinical models of antisocial behaviors (AB). However, assessments of CU traits within large-scale longitudinal and neurobiologically focused investigations remain remarkably sparse. We sought to develop a brief measure of CU traits using items from widely administered instruments that could be linked to neuroimaging, genetic, and environmental data within already existing datasets and future studies.
Methods
Data came from a large and diverse sample (n = 4525) of youth (ages~9–11) taking part in the Adolescent Brain and Cognitive Development (ABCD) Study. Moderated nonlinear factor analysis was used to assess measurement invariance across sex, race, and age. We explored whether CU traits were distinct from other indicators of AB, investigated unique links with theoretically-relevant outcomes, and replicated findings in an independent sample.
Results
The brief CU traits measure demonstrated strong psychometric properties and evidence of measurement invariance across sex, race, and age. On average, boys endorsed higher levels of CU traits than girls and CU traits were related to, yet distinguishable from other indicators of AB. The CU traits construct also exhibited expected associations with theoretically important outcomes. Study findings were also replicated across an independent sample of youth.
Conclusions
In a large, multi-site study, a brief measure of CU traits can be measured distinctly from other dimensions of AB. This measure provides the scientific community with a method to assess CU traits in the ABCD sample, as well as in other studies that may benefit from a brief assessment of CU.
This work characterizes Late Cretaceous calc-alkaline volcanic rocks in Gastre, Northern Patagonia, Argentina. These newly found porphyritic rocks bear an 40Ar–39Ar amphibole age of ~ 74–76 Ma, a subduction-type geochemical signature and a deep, garnet-bearing source. Extruded in a stage of low magmatic activity in the Northern Patagonian Andes (~ 41–44° S), they could represent an eastward migration of the Late Cretaceous magmatic arc that was associated with a regional compressive deformational stage in the South American margin.
Cannabis use has been linked to impairments in neuropsychological functioning across a large and continually expanding body of research. Yet insight into underlying causal relations remains limited due to the historically cross-sectional nature of studies in this area. Recently, however, studies have begun to use more informative design strategies to delineate these associations. The aim of this article is to provide a critical evaluation and review of research that uses longitudinal designs to examine the link between cannabis use and neuropsychological functioning. In summarizing the primary findings across these studies, this review suggests that cannabis use leads to neuropsychological decline. However, across most studies, these associations were modest, were present only for the group with the heaviest cannabis use, and were often attenuated (or no longer significant) after controlling for potential confounding variables. Future studies with neuropsychological data before and after initiation of cannabis use, along with careful measurement and control of “shared risk factors” between cannabis use and poorer neuropsychological outcomes, are needed to better understand who, and under what conditions, is most vulnerable to cannabis-associated neuropsychological decline. (JINS, 2017, 23, 893–902)