Search

IntroductionHumor as a valuable construct in psychology has been the subject of much discussion for many years and has received increased attention more recently in the field of positive psychology. However, empirical research on the application of humor in a clinical setting with depressed or anxious clients has been difficult to discover. Because of the potential benefits and the low costs of providing humorous interventions, our goal was to give an overview of the studies conducted in psychotherapy and to show the effect of humor on the levels of depression and anxiety symptoms. Furthermore, we wanted to assess the empiric support of humor as a clinical intervention in psychotherapy according to the SIGN system.MethodsWe used the PRISMA guidelines. Because of the differences in the design of the 10 included studies, it was not possible to perform a meta-analysis.ResultsResults from studies performed in seven different countries show that humorous interventions can have significant positive effects on symptoms of depression and anxiety. The results also confirm the prior observation that empirical research in the field is based on different designs with different populations and different methods of translating the abstract concept of humor into measurable observations. The results need to be considered with caution because of the methodological limitations of the research to date.DiscussionSome authors advocate for an integrative approach to continue research on humor in psychotherapy. It is our recommendation to first focus on the separate aspects of humor and to conduct research based on sound methodology. To initiate wider research to the application of humor in psychotherapy, we propose an approach to humorous interventions based on surprise and confusion which can help clients to search for an alternative framework to resolve the confusion and therefore promote taking on new perspectives and distancing themselves from the actual problem.

A tracking-free approach by Gnesotto et al. is developed to distinguish active and thermal fluctuations in microscopy data of non-equilibrium systems such as cell membranes. The method relies on a dimensional reduction scheme revealing a hierarchy of the most dissipative dynamical components.

Summary: Human Vδ2 cells are innate-like γδ T effectors performing potent immune surveillance against tumors. The constitutive expression of NKG2A identifies a subset of Vδ2 T cells licensed with an intrinsic hyper-responsiveness against cancer. Indeed, the transcriptomic profiles of NKG2A+ and NKG2A− cells characterize two distinct “intralineages” of Vδ2 T lymphocytes that appear early during development, keep their phenotypes, and show self-renewal capabilities in adult life. The hyper-responsiveness of NKG2A+ Vδ2 T cells is counterbalanced by the inhibitory signaling delivered by human leukocyte antigen E (HLA-E) expressed on malignant cells as a tumor-escape mechanism. However, either masking or knocking out NKG2A restores the capacity of Vδ2 T cells to exert the highest effector functions even against HLA-E+ tumors. This is highly relevant in the clinic, as the different degrees of engagement of the NKG2A-HLA-E checkpoint in hepatocellular carcinoma, glioblastoma, and non-small cell lung cancer directly impact patients’ overall survival. These findings open avenues for developing combined cellular and immunologic anticancer therapies.

The balance between self-renewal and differentiation is crucial to ensure the homeostasis of the hematopoietic system, and is a hallmark of hematopoietic stem cells. However, the underlying molecular pathways, including the role of micro-RNA, are not completely understood. To assess the contribution of micro-RNA, we performed micro-RNA profiling of hematopoietic stem cells and their immediate downstream progeny multi-potent progenitors from wild-type control and Pbx1-conditional knockout mice, whose stem cells display a profound self-renewal defect. Unsupervised hierarchical cluster analysis separated stem cells from multi-potent progenitors, suggesting that micro-RNA might regulate the first transition step in the adult hematopoietic development. Notably, Pbx1-deficient and wild-type cells clustered separately, linking micro-RNAs to self-renewal impairment. Differential expression analysis of micro-RNA in the physiological stem cell-to-multi-potent progenitor transition and in Pbx1-deficient stem cells compared to control stem cells revealed miR-127-3p as the most differentially expressed. Furthermore, miR-127-3p was strongly stem cell-specific, being quickly down-regulated upon differentiation and not re-expressed further downstream in the bone marrow hematopoietic hierarchy. Inhibition of miR-127-3p function in Lineage-negative cells, achieved through a lentiviral-sponge vector, led to severe stem cell depletion, as assessed with serial transplantation assays. miR-127-3p-sponged stem cells displayed accelerated differentiation, which was uncoupled from proliferation, accounting for the observed stem cell reduction. miR-127-3p overexpression in Lineage-negative cells did not alter stem cell pool size, but gave rise to lymphopenia, likely due to lack of miR-127-3p physiological downregulation beyond the stem cell stage. Thus, tight regulation of miR-127-3p is crucial to preserve the self-renewing stem cell pool and homeostasis of the hematopoietic system.

Thyroid hormone deficiency at early postnatal ages affects the cytoarchitecture and function of neocortical and telencephalic limbic areas, leading to impaired associative memory and in a wide spectrum of neurological and mental diseases. Neocortical areas project interhemispheric axons mostly through the corpus callosum and to a lesser extent through the anterior commissure (AC), while limbic areas mostly project through the AC and hippocampal commissures. Functional magnetic resonance data from children with late diagnosed congenital hypothyroidism and abnormal verbal memory processing, suggest altered ipsilateral and contralateral telencephalic connections. Gestational hypothyroidism affects AC development but the possible effect of transient and chronic postnatal hypothyroidism, as occurs in late diagnosed neonates with congenital hypothyroidism and in children growing up in iodine deficient areas, still remains unknown. We studied AC development using in vivo magnetic resonance imaging and electron microscopy in hypothyroid and control male rats. Four groups of methimazole (MMI) treated rats were studied. One group was MMI-treated from postnatal day (P) 0 to P21; some of these rats were also treated with L-thyroxine (T4) from P15 to P21, as a model for early transient hypothyroidism. Other rats were MMI-treated from P0 to P150 and from embryonic day (E) 10 to P170, as a chronic hypothyroidism group. The results were compared with age paired control rats. The normalized T2 signal using magnetic resonance image was higher in MMI-treated rats and correlated with the number and percentage of myelinated axons. Using electron microscopy, we observed decreased myelinated axon number and density in transient and chronic hypothyroid rats at P150, unmyelinated axon number increased slightly in chronic hypothyroid rats. In MMI-treated rats, the myelinated axon g-ratio and conduction velocity was similar to control rats, but with a decrease in conduction delays. These data show that early postnatal transient and chronic hypothyroidism alters AC maturation that may affect the transfer of information through the AC. The alterations cannot be recovered after delayed T4-treatment. Our data support the neurocognitive delay found in late T4-treated children with congenital hypothyroidism.

Massimo Sabbatini,1 Gianluca Garofalo,1 Silvio Borrelli,2 Sossio Vitale,1 Massimiliano Torino,1 Domenico Capone,3 Luigi Russo,3 Antonio Pisani,1 Rosa Carrano,1 Riccardo Gallo,1 Stefano Federico11Nephrology, Department of Public Health, University Federico II of Naples, 2Department of Nephrology, Second University of Naples, 3Department of Neurosciences, Unit of Clinical Pharmacology, University Federico II of Naples, Naples, ItalyPurpose: The aim of this study was to determine the prevalence of nonadherence in a cohort of renal transplant recipients (RTRs) and to evaluate prospectively whether more intense clinical surveillance and reduced pill number enhanced adherence.Patients and methods: The study was carried out in 310 stable RTRs in whom adherence, life satisfaction, and transplant care were evaluated by specific questionnaires (time 0). The patients under tacrolimus (TAC; bis in die [BID]) were then shifted to once-daily TAC (D-TAC) to reduce their pill burden (Shift group) and were followed up for 6 months to reevaluate the same parameters. Patients on cyclosporin or still on BID-TAC constituted a time-control group.Results: The prevalence of nonadherence was 23.5% and was associated with previous rejection episodes (P

We investigate the influence of the material in homogeneities that are generated by an isotropic growth on the source of mass acting within a growing living tissue. In order to do that, we need to study the interaction between these material in homogeneities and the chemical agents dissolved within the tissue. For this purpose, we use some ideas and methods from Condensed Matter Physics (e.g., the Path Integral technique employed in modeling Brownian processes) and apply them to the Continuum Mechanics description of volumetric Growth. We believe that this approach may provide new physical insight into the interactions between the macroscopic dynamics of living systems and the evolution of the subsystems which activate biological processes.

Altered expression and function of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) has been associated with several diseases such as endothelial dysfunction, atherosclerosis and obesity. In these pathologies, oxLDL/LOX-1 activates signaling pathways that promote cell proliferation, cell motility and angiogenesis. Recent studies have indicated that olr1 mRNA is over-expressed in stage III and IV of human prostatic adenocarcinomas. However, the function of LOX-1 in prostate cancer angiogenesis remains to be determined. Our aim was to analyze the contribution of oxLDL and LOX-1 to tumor angiogenesis using C4-2 prostate cancer cells. We analyzed the expression of pro-angiogenic molecules and angiogenesis on prostate cancer tumor xenografts, using prostate cancer cell models with overexpression or knockdown of LOX-1 receptor. Our results demonstrate that the activation of LOX-1 using oxLDL increases cell proliferation, and the expression of the pro-angiogenic molecules VEGF, MMP-2, and MMP-9 in a dose-dependent manner. Noticeably, these effects were prevented in the C4-2 prostate cancer model when LOX-1 expression was knocked down. The angiogenic effect of LOX-1 activated with oxLDL was further demonstrated using the aortic ring assay and the xenograft model of tumor growth on chorioallantoic membrane of chicken embryos. Consequently, we propose that LOX-1 activation by oxLDL is an important event that enhances tumor angiogenesis in human prostate cancer cells.

This paper studies the impact of skilled immigration policy frictions in the United States on technology-intensive firms by age cohorts. We use firm-level data and a general equilibrium model with endogenous firm entry and exit. The empirical results show that skilled immigration policy frictions directly influence young firm dynamics in technology-intensive sectors by affecting firm survival. Our general equilibrium model incorporates skilled foreign labor and immigration policy frictions that mimic the H-1B policy and matches the age distribution of firms in high- technology sectors, showing also that increased entry of younger firms leads to a greater exit of older firms. JEL classification: F22, M13 Key words: skilled immigration, start-ups, high-technology firms, firm dynamics https://doi.org/ 10.29338/wp2024-02, 1 Introduction Skilled immigration policies in the United States, notably those involving the H-1B visa program, impose well-known frictions on firms. This program, the largest channel for hiring temporary foreign [...]

We document a slowdown in low-skilled immigration that began around the onset of the Great Recession in 2007, which was associated with a subsequent rise in low- skilled wages, a decline in the skill premium, and labor shortages in service occupations. Falling returns to education also coincided with a decline in the educational attainment of native workers. We then develop and estimate a stochastic growth model with endogenous immigration and training to rationalize these facts. Lower immigration leads to higher wages for low-skilled workers but also to higher consumer prices and lower aggregate consumption. Importantly, the decline in the skill premium reduces the incentive to train native workers and hurts aggregate productivity over time, which reduces welfare. We assess the implications of stimulus policies implemented during the COVID-19 pandemic and show that the shortage of low-skilled immigrant labor amplified the increase in consumer prices, partially eroding the effectiveness of stimulus. JEL classification: F16, F22, F41 Key words: international labor migration, skill premium, task upgrading, heterogeneous workers, 1 Introduction We document the protracted slowdown in low-skill immigration since the Great recession in 2007 and study its impact on labor market dynamics, macroeconomic performance and welfare. We first [...]

These guidelines are a consensus work of a considerable number of members of the immunology and flow cytometry community. They provide the theory and key practical aspects of flow cytometry enabling immunologists to avoid the common errors that often undermine immunological data. Notably, there are comprehensive sections of all major immune cell types with helpful Tables detailing phenotypes in murine and human cells. The latest flow cytometry techniques and applications are also described, featuring examples of the data that can be generated and, importantly, how the data can be analysed. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid, all written and peer-reviewed by leading experts in the field, making this an essential research companion.

The molecular mechanisms responsible for the high immunosuppressive capacity of [CD4.sup.+] Tregs in tumors are not well known. High-dimensional single-cell profiling of T cells from chemotherapy-naive individuals with non-small-cell lung cancer identified the transcription factor IRF4 as specifically expressed by a subset of intratumoral [CD4.sup.+] effector Tregs with superior suppressive activity. In contrast to the [IRF4.sup.-] counterparts, [IRF4.sup.+] Tregs expressed a vast array of suppressive molecules, and their presence correlated with multiple exhausted subpopulations of T cells. Integration of transcriptomic and epigenomic data revealed that IRF4, either alone or in combination with its partner BATF, directly controlled a molecular program responsible for immunosuppression in tumors. Accordingly, deletion of Irf4 exclusively in Tregs resulted in delayed tumor growth in mice while the abundance of IRF4+ Tregs correlated with poor prognosis in patients with multiple human cancers. Thus, a common mechanism underlies immunosuppression in the tumor microenvironment irrespective of the tumor type., Introduction Despite recent clinical breakthroughs in adoptive T cell transfer approaches and checkpoint blockade in treating hematopoietic and solid tumors, suppression of the antitumor immune response in the tumor microenvironment [...]

We develop a quantitative business cycle model with search complementarities in the interfirm matching process that entails a multiplicity of equilibria. An active equilibrium with strong joint venture formation, large output, and low unemployment coexists with a passive equilibrium with low joint venture formation, low output, and high unemployment. Changes in fundamentals move the system between the two equilibria, generating large and persistent business cycle fluctuations. The volatility of shocks is important for the selection and duration of each equilibrium. Sufficiently adverse shocks in periods of low macroeconomic volatility trigger severe and protracted downturns. The magnitude of government intervention is critical to foster economic recovery in the passive equilibrium, while it plays a limited role in the active equilibrium. JEL classification: C63, C68, E32, E37, E44, G12 Key words: aggregate fluctuations, strategic complementarities, macroeconomic volatility, government spending, 1 Introduction Search often involves two parties. Workers search for firms and firms search for workers. Customers search for shops and shops search for customers. Entrepreneurs search for venture capitalists [...]

We build a model with a traditional banking system, endogenous entry of firms and fintech intermediaries, and firm heterogeneity in credit access and usage to study the credit-market, macroeconomic, and business cycle implications of the recent sizable growth in the number of fintech intermediaries in emerging economies. Our analysis delivers three findings. First, the impact of greater fintech entry on firm financial inclusion depends on whether greater entry is driven by lower entry costs for fintech intermediaries or lower barriers to fintech credit for unbanked firms. Second, greater fintech entry can have positive long-term macroeconomic effects. Third, greater fintech entry leads to a reduction in output volatility but results in greater relative volatility in bank credit and consumption. The effects of fintech entry on macro outcomes and volatility hinge critically on the interaction between domestic financial shocks and the reduction in fintech lending rates stemming from greater fintech entry. Unless greater fintech entry leads to lower fintech credit costs for firms, greater fintech entry will have no meaningful credit-market or business-cycle consequences. JEL classification: E24, E32, E44, F41, G21 Key words: financial access and participation, endogenous firm entry, banking sector, fintech entry, emerging economy business cycles, Working Paper 2022-2 January 2022 1 Introduction It is well known that firms in emerging economies (EMEs) face significant barriers to accessing formal credit, resulting in much lower shares of [...]

This paper develops a dynamic general equilibrium model with heterogeneous firms that face search complementarities in the formation of vendor contracts. Search complementarities amplify small differences in productivity among firms. Market concentration fosters monopsony power in the labor market, magnifying profits and further enhancing the output share of high-productivity firms. The combination of search complementarities and monopsony power induce a strong 'Matthew effect' that endogenously generates superstar firms out of uniform idiosyncratic productivity distributions. Reductions in search costs increase market concentration, lower the labor income share, and increase wage inequality. The model also transforms short-lived negative aggregate shocks into persistent recessions that heighten market concentration. JEL classification: C63, C68, E32, E37, E44, G12 Key words: market concentration, superstar firms, search complementarities, monopsony power in the labor market, Working Paper 2021-4 January 2021 1 Introduction Merton (1968) famously identified the 'Matthew effect': For whoever has will be given more, and they will have an abundance. Whoever does not [...]

Abstract Background This study examined psychiatric hospitalisation patterns in San Salvatore Hospital in L’ Aquila (Italy), during two major crises: the 2009 earthquake and the COVID-19 pandemic lockdown. The investigation spans two four-year periods, from 2008 to 2011 and from 2019 to 2022, with a focus on the trimester around the earthquake and the first wave/lockdown of the pandemic. Methods We analysed weekly psychiatric unit admissions of adults diagnosed with schizophrenia spectrum disorder, major depression, bipolar disorder, and alcohol/substance use disorder. Four-year periods around the Earthquake and COVID-19 Lockdown were divided into sixteen trimesters, and Generalised linear models were used to analyse the relationship between weekly hospitalisation frequency and trimesters by diagnosis using a Poisson distribution. Results A total of 1195 and 1085 patients were admitted to the psychiatric ward in the 2008–2011 and 2019–2022 periods, respectively. Weekly hospitalisations in the earthquake trimester were lower than during the previous one for all diagnoses (schizophrenia spectrum: −41.9%, p = 0.040; major depression: −56.7%, p = 0.046; bipolar disorder: −69.1%, p = 0.011; alcohol/substance use disorder: −92.3%, p = 0.013). This reduction persisted for 21, 18, and 33 months after the earthquake for schizophrenia spectrum, bipolar, and alcohol/substance use disorders, respectively. Contrarily, patterns of weekly admissions around the COVID-19 lockdown remained substantially stable in the short term. However, a consistent long-term hospitalisation increase for all diagnoses characterised the first half of 2022 (the cessation of anti-COVID-19 measures; schizophrenia spectrum: +68.6%, p = 0.014; major depression: +133.3%, p = 0.033; bipolar disorder: +180.0%, p = 0.034; alcohol/substance use disorder: +475.0%, p = 0.001). Conclusions The present study indicated that exposure to major health crises can have both short- and long-term effects on psychiatric ward admission, holding significant implications for current and future major health emergency management strategies.

Abstract The East African Rift is one of Earth’s largest continental landforms. It is recognized as a critical region for understanding hominin evolution yet has also undergone important transformation through ongoing tectonic and volcanic activity. An understanding of the interplay of rift kinematics, magma genesis and geomorphic evolution requires firm geochronology but this has been lacking for much of the East African Rift. Here we present detailed stratigraphic observations and high-precision 40Ar/39Ar ages for major volcanic units in the Central Main Ethiopian Rift. Our new data identify a volumetrically major episode of explosive volcanism between circa 3.85–3.42 million years ago, after aproximately 5-million years-long quiescence. Four other pulses followed but with intensity and magnitude declining over time. We suggest that the observed temporal clustering and the pulsatory volcanic activity may have influenced environmental conditions in the area, with possible implications for hominin evolution.

Abstract Iodine and bromine play central roles in polar atmospheric chemistry: iodine influences the atmospheric oxidative capacity and can generate cloud condensation nuclei, while bromine participates in ozone depletion reactions, known as bromine explosions. Here we present a very sensitive analytical method for Br and I speciation by coupling the ion chromatography system (IC) with an inductively coupled plasma sector field mass spectrometer (ICP-SFMS). We achieved sub-picogram-per gram (pg g−1) as limits of detection (LODs) ranging from 0.4 pg g−1 for I−, 0.8 pg g−1 for IO3 −, 4 pg g−1 for Br−, and 1 pg g−1 for BrO3 −, respectively. These values represent a decrease of up to 30 times compared to the LODs reported in other studies. The method was validated using deep snow samples from the Svalbard Islands, collected at the end of the polar night to quantify various oxidized compounds during their seasonal minimum. In the future, this method could prove useful in the paleoclimatic study of ice cores and snow, as well as in ice chemistry research.

Abstract Background Positional plagiocephaly is an asymmetrical flattened skull deformity whose incidence increased significantly in the last decades. Osteopathic treatment has been suggested to tackle early deformational sequences, in order to ensure the correct development of the child. The aim of the study was to assess the effectiveness of osteopathic treatment of positional cranial deformities in infants. Methods Retrospective observational study carried out at the Section of Neonatology and Neonatal Intensive Care Unit of the Department of Interdisciplinary Medicine of University of Bari, Italy in collaboration with a specialized pediatric osteopath. Results 424 infants were enrolled. Isolated positional plagiocephaly affected the vast majority of infants (n. 390, 91.98%); 34 patients (8.02%) were diagnosed with positional brachycephaly. Both infant groups (positional plagiocephaly and positional brachycephaly) had a median severity score of 3 (IQR: 3 – 3 and 2 – 3, respectively) and benefited from a median of 3 osteopathic sessions (IQR 3–4 and 2–4, respectively). Higher severity scores of positional asymmetries were significantly more common in preterm neonates (Pearson chi2: 11.58; p-value: 0.021) and in males (Pearson chi2: 10.06; p-value: 0.039). Conclusions Significant improvements in positional cranial deformations of children were obtained after only five osteopathic treatments provided in the first months of life. The osteopathic treatment could positively impact the clinical history of patients with positional plagiocephaly and positional brachycephaly. Implication for practice • Positional plagiocephaly is increasingly common among infants and may cause moderate to severe neurodevelopmental adverse effects. • Osteopathic treatment may tackle early deformational sequences, in order to ensure the correct development of the child. • Our study reveals that cranial asymmetry of infants with positional plagiocephaly is significantly reduced after only five osteopathic treatments provided in the first months of life. • Osteopathic treatment should be offered as a first line approach to young infants diagnosed with positional plagiocephaly.