Two-dimensional heavy fermions in the van der Waals metal CeSiI.

Heavy-fermion metals are prototype systems for observing emergent quantum phases driven by electronic interactions1-6. A long-standing aspiration is the dimensional reduction of these materials to exert control over their quantum phases7-11, which remains a significant challenge because traditional intermetallic heavy-fermion compounds have three-dimensional atomic and electronic structures. Here we report comprehensive thermodynamic and spectroscopic evidence of an antiferromagnetically ordered heavy-fermion ground state in CeSiI, an intermetallic comprising two-dimensional (2D) metallic sheets held together by weak interlayer van der Waals (vdW) interactions. Owing to its vdW nature, CeSiI has a quasi-2D electronic structure, and we can control its physical dimension through exfoliation. The emergence of coherent hybridization of f and conduction electrons at low temperature is supported by the temperature evolution of angle-resolved photoemission and scanning tunnelling spectra near the Fermi level and by heat capacity measurements. Electrical transport measurements on few-layer flakes reveal heavy-fermion behaviour and magnetic order down to the ultra-thin regime. Our work establishes CeSiI and related materials as a unique platform for studying dimensionally confined heavy fermions in bulk crystals and employing 2D device fabrication techniques and vdW heterostructures12 to manipulate the interplay between Kondo screening, magnetic order and proximity effects.

A few-layer covalent network of fullerenes.

The two natural allotropes of carbon, diamond and graphite, are extended networks of sp3-hybridized and sp2-hybridized atoms, respectively1. By mixing different hybridizations and geometries of carbon, one could conceptually construct countless synthetic allotropes. Here we introduce graphullerene, a two-dimensional crystalline polymer of C60 that bridges the gulf between molecular and extended carbon materials. Its constituent fullerene subunits arrange hexagonally in a covalently interconnected molecular sheet. We report charge-neutral, purely carbon-based macroscopic crystals that are large enough to be mechanically exfoliated to produce molecularly thin flakes with clean interfaces-a critical requirement for the creation of heterostructures and optoelectronic devices2. The synthesis entails growing single crystals of layered polymeric (Mg4C60)∞ by chemical vapour transport and subsequently removing the magnesium with dilute acid. We explore the thermal conductivity of this material and find it to be much higher than that of molecular C60, which is a consequence of the in-plane covalent bonding. Furthermore, imaging few-layer graphullerene flakes using transmission electron microscopy and near-field nano-photoluminescence spectroscopy reveals the existence of moiré-like superlattices3. More broadly, the synthesis of extended carbon structures by polymerization of molecular precursors charts a clear path to the systematic design of materials for the construction of two-dimensional heterostructures with tunable optoelectronic properties.

Heterointerface effects in the electrointercalation of van der Waals heterostructures.

Molecular-scale manipulation of electronic and ionic charge accumulation in materials is the backbone of electrochemical energy storage1-4. Layered van der Waals (vdW) crystals are a diverse family of materials into which mobile ions can electrochemically intercalate into the interlamellar gaps of the host atomic lattice5,6. The structural diversity of such materials enables the interfacial properties of composites to be optimized to improve ion intercalation for energy storage and electronic devices7-12. However, the ability of heterolayers to modify intercalation reactions, and their role at the atomic level, are yet to be elucidated. Here we demonstrate the electrointercalation of lithium at the level of individual atomic interfaces of dissimilar vdW layers. Electrochemical devices based on vdW heterostructures 13 of stacked hexagonal boron nitride, graphene and molybdenum dichalcogenide (MoX2; X = S, Se) layers are constructed. We use transmission electron microscopy, in situ magnetoresistance and optical spectroscopy techniques, as well as low-temperature quantum magneto-oscillation measurements and ab initio calculations, to resolve the intermediate stages of lithium intercalation at heterointerfaces. The formation of vdW heterointerfaces between graphene and MoX2 results in a more than tenfold greater accumulation of charge in MoX2 when compared to MoX2/MoX2 homointerfaces, while enforcing a more negative intercalation potential than that of bulk MoX2 by at least 0.5 V. Beyond energy storage, our combined experimental and computational methodology for manipulating and characterizing the electrochemical behaviour of layered systems opens new pathways to control the charge density in two-dimensional electronic and optoelectronic devices.

Non-COVID-19 hospitalization and mortality during the COVID-19 pandemic in Iran: a longitudinal assessment of 41 million people in 2019-2022.

BACKGROUND: During a COVID-19 pandemic, it is imperative to investigate the outcomes of all non-COVID-19 diseases. This study determines hospital admissions and mortality rates related to non-COVID-19 diseases during the COVID-19 pandemic among 41 million Iranians. METHOD: This nationwide retrospective study used data from the Iran Health Insurance Organization. From September 23, 2019, to Feb 19, 2022, there were four study periods: pre-pandemic (Sept 23-Feb 19, 2020), first peak (Mar 20-Apr 19, 2020), first year (Feb 20, 2020-Feb 18, 2021), and the second year (Feb 19, 2021-Feb 19, 2022) following the pandemic. Cause-specific hospital admission and in-hospital mortality are the main outcomes analyzed based on age and sex. Negative binomial regression was used to estimate the monthly adjusted Incidence Rate Ratio (IRR) to compare hospital admission rates in aggregated data. A logistic regression was used to estimate the monthly adjusted in-hospital mortality Odds Ratio (OR) for different pandemic periods. RESULTS: During the study there were 6,522,114 non-COVID-19 hospital admissions and 139,679 deaths. Prior to the COVID-19 outbreak, the standardized hospital admission rate per million person-month was 7115.19, which decreased to 2856.35 during the first peak (IRR 0.40, [0.25-0.64]). In-hospital mortality also increased from 20.20 to 31.99 (OR 2.05, [1.97-2.13]). All age and sex groups had decreased admission rates, except for females at productive ages. Two years after the COVID-19 outbreak, the non-COVID-19 hospital admission rate (IRR 1.25, [1.13-1.40]) and mortality rate (OR 1.05, [1.04-1.07]) increased compared to the rates before the pandemic. The respiratory disease admission rate decreased in the first (IRR 0.23, [0.17-0.31]) and second years (IRR 0.35, [0.26-0.47] compared to the rate before the pandemic. There was a significant reduction in hospitalizations for pneumonia (IRR 0.30, [0.21-0.42]), influenza (IRR 0.04, [0.03-0.06]) and COPD (IRR 0.39, [0.23-0.65]) during the second year. There was a significant and continuous rise in the hematological admission rate during the study, reaching 186.99 per million person-month in the second year, reflecting an IRR of 2.84 [2.42-3.33] compared to the pre-pandemic period. The mortality rates of mental disorders (OR 2.15, [1.65-2.78]) and musculoskeletal (OR 1.48, [1.20-1.82), nervous system (OR 1.42, [1.26-1.60]), metabolic (OR 1.99, [1.80-2.19]) and circulatory diseases (OR 1.35, [1.31-1.39]) increased in the second year compare to pre-pandemic. Myocardial infarction (OR 1.33, [1.19-1.49]), heart failure (OR 1.59, [1.35-1.87]) and stroke (OR 1.35, [1.24-1.47]) showed an increase in mortality rates without changes in hospitalization. CONCLUSIONS: In the era of COVID-19, the changes seem to have had a long-term effect on non-COVID-19 diseases. Countries should prepare for similar crises in the future to ensure medical services are not suspended.

Overutilization of head computed tomography in cases of mild traumatic brain injury: a systematic review and meta-analysis.

Head computed tomography (CT) is the preferred imaging modality for mild traumatic brain injury (mTBI). The routine use of head CT in low-risk individuals with mild TBI offers no clinical benefit but also causes notable health and financial burden. Despite the availability of related guidelines, studies have reported considerable rate of non-indicated head CT requests. The objectives were to provide an overall estimate for the head CT overutilization rate and to identify the factors contributing to the overuse. A systematic review of PubMed, Scopus, Web of Science, and Embase databases was conducted up to November 2023, following PRISMA and MOOSE guidelines. Two reviewers independently selected eligible articles and extracted data. Quality assessment was performed using a bias risk tool, and a random-effects model was used for data synthesis. Fourteen studies, encompassing 28,612 patients, were included, with 27,809 undergoing head CT scans. Notably, 75% of the included studies exhibited a moderate to high risk of bias. The overutilization rate for pediatric and adult patients was 27% (95% CI: 5-50%) and 32% (95% CI: 21-44%), respectively. An alternative rate, focusing on low-risk pediatric patients, was 54% (95% CI: 20-89%). Overutilization rates showed no significant difference between teaching and non-teaching hospitals. Patients with mTBI from falls or assaults were less likely to receive non-indicated scans. There was no significant association between physician specialty or seniority and overuse, nor between patients' age or sex and the likelihood of receiving a non-indicated scan. Approximately one-third of head CT scans in mTBI cases are avoidable, underscoring the necessity for quality improvement programs to reduce unnecessary imaging and its associated burdens.

Chloroaluminate Anion Intercalation in Graphene and Graphite: From Two-Dimensional Devices to Aluminum-Ion Batteries.

A rechargeable aluminum-ion battery based on chloroaluminate electrolytes has received intense attention due to the high abundance and chemical stability of aluminum. However, the fundamental intercalation processes and dynamics in these battery systems remain unresolved. Here, the energetics and dynamics of chloroaluminate ion intercalation in atomically thin single crystal graphite are investigated by fabricating mesoscopic devices for charge transport and operando optical microscopy. These mesoscopic measurements are compared to the high-performance rechargeable Al-based battery consisting of a few-layer graphene-multiwall carbon nanotube composite cathode. These composites exhibit a 60% capacity enhancement over pyrolytic graphite, while an ∼3-fold improvement in overall ion diffusivity is also obtained exhibiting ∼1% of those in atomically thin single crystals. Our results thus establish the distinction between intrinsic and ensemble electrochemical behavior in Al-based batteries and show that engineering ion transport in these devices can yet lead to vast improvements in battery performance.

Analysis of the strategies used by iranian nurses for management of provided care for patients with COVID- 19: a qualitative study.

BACKGROUND: Nurses have been at the center of managing the COVID-19 outbreak through direct bedside care in respiratory, emergency and intensive care environments, managing hospital units, providing Covid-19 testing, vaccination and contact tracing. Thus, the present study aimed to analysis the strategies used by Iranian nurses for management of Provided Care for patients with COVID- 19. METHODS: The present study was conducted based on the conventional content analysis method and Graneheim & Lundman approach. The participants included the nurses working in the COVID-19 wards and were recruited by purposeful sampling and based on inclusion criteria. The data were collected by conducting semi-structured, in-depth, one-to-one interviews until reaching data saturation. RESULTS: In-depth interviews with 10 nurses represented four main categories and fifteen subcategories. Four main categories emerged in this study i.e. "justice in human resources management", "The art and science of comprehensive nursing care", "managers as agents of change in crisis" and "challenges and its management". CONCLUSION: The nurses' experiences of management strategies showed that paying attention to the financial, psychological, educational, equipment needs of nurses and maintaining their safety make the suitable environment for providing high quality care for patients with covid-19.

The cross-talk between soluble "Find me" and "Keep out" signals as an initial step in regulating efferocytosis.

The rapid clearance of apoptotic cells (ACs), known as efferocytosis, prompts the inhibition of inflammatory responses and autoimmunity and maintains homeostatic cell turnover by controlling the release of intracellular contents. The fast clearance of ACs requires professional and nonprofessional phagocytic cells that can accurately and promptly recognize ACs and migrate towards them. Cells undergoing apoptosis alarm their presence by releasing special soluble chemotactic factors, such as lactoferrin, that act as "Find me," "Keep out," or "Stay away" signals to recruit phagocytic cells, such as macrophages or prevent granulocyte migration. Efferocytosis effectively serves to prevent damage-associated molecular pattern release and secondary necrosis and inhibit inflammation/autoimmunity at the very first step. Since less attention has been given to the cross-talk and balance of "Find me" and "Keep out" signals released from ACs in efferocytosis, we set out to investigate the current knowledge of the roles of "Find me" and "Keep out" signals in the efferocytosis process.

Topology predicts long-term functional outcome in early psychosis.

Early intervention in psychosis is crucial to improving patient response to treatment and the functional deficits that critically affect their long-term quality of life. Stratification tools are needed to personalize functional deficit prevention strategies at an early stage. In the present study, we applied topological tools to analyze symptoms of early psychosis patients, and detected a clear stratification of the cohort into three groups. One of the groups had a significantly better psychosocial outcome than the others after a 3-year clinical follow-up. This group was characterized by a metabolic profile indicative of an activated antioxidant response, while that of the groups with poorer outcome was indicative of oxidative stress. We replicated in a second cohort the finding that the three distinct clinical profiles at baseline were associated with distinct outcomes at follow-up, thus validating the predictive value of this new stratification. This approach could assist in personalizing treatment strategies.

Economic burden of major depressive disorder: a case study in Southern Iran.

BACKGROUND: Depression disorders are a leading cause of disability in the world which imposes a significant economic burden on patients and societies The present study aimed to determine the economic burden of Major Depressive Disorder (MDD) on the patients referred to the reference psychiatric single-specialty hospitals in southern Iran in 2020. METHODS: This cross-sectional research is a partial economic evaluation and a cost-of-illness study conducted in southern Iran in 2020. A total of 563 patients were enrolled through the census method, and a researcher-made data collection form was used to gather the required information. The prevalence-based and the bottom-up approaches were also used to collect the cost information and calculate the costs, respectively. The data on direct medical, direct non-medical, and indirect costs were obtained using the information in the patients' medical records and insurance bills as well as their self-reports or those of their companions. To calculate the indirect costs, the human capital approach was used as well. RESULTS: The results showed that the annual cost of MDD was $ 2717.41 Purchasing Power Parity (PPP) (USD 2026.13) per patient in 2020. Direct medical costs accounted for the largest share of the costs (73.68%), of which hoteling and regular beds expenses were the highest (57.70% of the total direct medical costs). The shares of direct non-medical and indirect costs were 7.52 and 18.80%, respectively, and the economic burden of the disease in the country was estimated at $7,120,456,596 PPP (USD 5,309,088,699). CONCLUSION: In general, due to the high prevalence of MDD and the chronicity of the disease, the costs of its treatment can impose a heavy economic burden on the society, healthcare system, insurance system, and the patients themselves. Therefore, it is suggested that health policymakers and managers should take appropriate measures to increase the basic and supplemental insurance coverage of these patients. In addition, in order to reduce the costs, proper and equitable distribution of psychiatrists and psychiatric beds, expansion of home care services, and use of Internet-based technologies and the cyberspace to follow up the treatment of these patients are recommended.

The role of efferocytosis in neuro-degenerative diseases.

Efferocytosis has a critical role in maintaining tissues and organs' homeostasis by removing apoptotic cells. It is essential for human health, and disturbances in efferocytosis may result indifferent illnesses. In case of inadequate clearance of the dead cells, the content in the cells would be released. In fact, it induces some damages to the tissue and leads to the prolonged inflammation, so unsuitable phagocytosis of the apoptotic cells is involved in occurrence as well as expansion of numerous human chronic inflammatory diseases. Studies have shown age dependence of the neuro-degenerative diseases, which are largely due to the neuro-inflammation and the loss of neurons and thus cause the brain's functional disorders. Efferocytosis is coupled to anti-inflammatory responses that contribute to the elimination of the dying neurons in neuro-degenerative diseases, so its disruption may make a risk factor in numerous human chronic inflammatory diseases such as multiple sclerosis, Alzheimer's disease, glioblastoma, and Rett syndrome. This study is a review of the efferocytosis molecular pathways and their role in neuro-degenerative diseases in order to discover a new treatment option to cure patients.

Cost-effectiveness analysis of hearing screening program for primary school children in southern Iran, Shiraz.

BACKGROUND: Hearing loss is the second most common chronic disease, the diagnosis and treatment of which can be faster through screening. In addition, early interventions will save significant costs for the education and health systems. Therefore, the present study aimed to evaluate the cost-effectiveness of hearing screening for primary school children in Shiraz. METHODS: This cross-sectional economic evaluation of cost-effectiveness was conducted from the perspective of the health system. The study population comprised all seven-year-old children participating in the screening program in Shiraz. The present study dealt only with direct costs. The expected costs and outcomes, as well as the ICER index were estimated using the decision tree model. The study outcomes included averted disability-adjusted life years (DALY) and true identification of hearing loss cases. The robustness of the results was evaluated using the one-way sensitivity analysis. The TreeAge 2020 and Excel 2016 software were also used to analyze the collected data. RESULTS: The hearing screening data obtained during 6 years (2015-2020) showed that every year, an average of 22,853 children in Shiraz were examined for hearing, of which 260 were true positive (%1.1). The costs of screening and lack of screening were estimated at $30.32 Purchasing Power Parity (PPP) and $13.75 PPP per child, respectively. The averted DALY due to performing hearing screening was estimated at 7 years for each child. The ICER was positive and equal to $ 0.06 PPP for the identified cases and $ 2.37 PPP per averted DALY. The sensitivity analysis confirmed the robustness of the results. CONCLUSIONS: According to the results, although hearing screening for primary school children had more costs and effectiveness, it was considered cost-effective. Therefore, universal screening with high quality and accuracy is recommended.

Cost-effectiveness analysis of rituximab versus natalizumab in patients with relapsing remitting multiple sclerosis.

INTRODUCTION: Multiple sclerosis (MS) is an inflammatory disease in which the myelin sheaths of the nerve cells in the brain and spinal cord, which are responsible for communication, are destroyed and cause physical signs and symptoms. According to studies, anti-CD20 monoclonal antibodies have significant results in the treatment of this disease. Thus, the aim of the present study was to determine the cost-effectiveness of rituximab against natalizumab in the patients with RRMS in southern Iran in 2020. METHODS: This is an economic evaluation including cost-effectiveness analysis in which the Markov model with a lifetime horizon was used. The study sample consisted of 120 patients randomly selected from among those referred to the MS Association and the Special Diseases Unit of Shiraz University of Medical Sciences. In this study, the costs were collected from a societal perspective, and the outcomes were obtained in the form of Quality Adjusted Life Years (QALY) and the mean relapse rate. The TreeAge pro 2020 and Excel 2016 software were used for data analysis. RESULTS: The comparative study of rituximab and natalizumab showed that the patients receiving rituximab had lower costs ($ 58,307.93 vs. $ 354,174.85) and more QALYs (7.77 vs. 7.65). In addition, the incidence of relapse by rituximab was lower compared to natalizumab (1.15 vs. 2.57). The probabilistic one-way sensitivity analysis showed the robustness of the results. The scatter plots also showed that rituximab was more cost-effective for the patients in 100% of the simulations for the threshold of < $ 37,641. DISCUSSION AND CONCLUSION: According to the results of this study, rituximab had higher cost-effectiveness than natalizumab. Therefore, it could be a priority for RRMS patients compared to natalizumab because it reduced treatment costs and increased effectiveness.

Virus, Exosome, and MicroRNA: New Insights into Autophagy.

Autophagy is known as a conserved self-eating mechanism that contributes to cells to degrade different intracellular components (i.e., macromolecular complexes, aggregated proteins, soluble proteins, organelles, and foreign bodies). Autophagy needs formation of a double-membrane structure, which is composed of the sequestered cytoplasmic contents, called autophagosome. There are a variety of internal and external factors involved in initiation and progression of autophagy process. Viruses as external factors are one of the particles that could be associated with different stages of this process. Viruses exert their functions via activation and/or inhibition of a wide range of cellular and molecular targets, which are involved in autophagy process. Besides viruses, a variety of cellular and molecular pathways that are activated and inhibited by several factors (e.g., genetics, epigenetics, and environment factors) are related to beginning and developing of autophagy mechanism. Exosomes and microRNAs have been emerged as novel and effective players anticipated in various stages of autophagy. More knowledge in these pathways and identification of accurate roles of them could help to provide better therapeutic approaches in several diseases such as cancer. We highlighted the roles of viruses, exosomes, and microRNAs in the autophagy processes.

Major depression subtypes are differentially associated with migraine subtype, prevalence and severity.

OBJECTIVE: Migraine and major depressive disorder show a high rate of comorbidity, but little is known about the associations between the subtypes of major depressive disorder and migraine. In this cross-sectional study we aimed at investigating a) the lifetime associations between the atypical, melancholic, combined and unspecified subtype of major depressive disorder and migraine with and without aura and b) the associations between major depressive disorder and its subtypes and the severity of migraine. METHODS: A total of 446 subjects with migraine (migraine without aura: n = 294; migraine with aura: n = 152) and 2511 controls from the population-based CoLaus/PsyCoLaus study, Switzerland, were included. Associations between major depressive disorder subtypes and migraine characteristics were tested using binary logistic or linear regression. RESULTS: Melancholic, combined and unspecified major depressive disorder were associated with increased frequency of migraine with aura, whereas only melancholic major depressive disorder was associated with increased frequency of migraine without aura. Lifetime and unspecified major depressive disorder were associated with severe migraine intensity among subjects with migraine with aura but not migraine without aura, while combined major depressive disorder was associated with higher migraine frequency independently from migraine subtype. CONCLUSION: This study suggests that melancholic but not atypical major depressive disorder is associated with migraine and migraine subtypes. Future studies exploring pathophysiological mechanisms shared between melancholic depression and migraine are warranted.

A pharmacogenetic risk score for the evaluation of major depression severity under treatment with antidepressants.

The severity of symptoms as well as efficacy of antidepressants in major depressive disorder (MDD) is modified by single nucleotide polymorphisms (SNPs) in different genes, which may contribute in an additive or synergistic fashion. We aimed to investigate depression severity in participants with MDD under treatment with antidepressants in relation to the combinatory effect of selected genetic variants combined using a genetic risk score (GRS). The sample included 150 MDD patients on regular AD therapy from the population-based Swiss PsyCoLaus cohort. We investigated 44 SNPs previously associated with antidepressant response by ranking them with regard to their association to the Center for Epidemiologic Studies Short Depression Scale (CES-D) score using random forest. The three top scoring SNPs (rs12248560, rs878567, rs17710780) were subsequently combined into an unweighted GRS, which was included in linear and logistic regression models using the CES-D score, occurrence of a major depressive episode (MDE) during follow-up and regular antidepressant treatment during the 6 months preceding follow-up assessment as outcomes. The GRS was associated with MDE occurrence (p = .02) and ln CES-D score (p = .001). The HTR1A rs878567 variant was associated with ln CES-D after adjustment for demographic and clinical variables [p = .02, lower scores for minor allele (G) carriers]. Additionally, rs12248560 (CYP2C19) CC homozygotes showed a six-fold higher likelihood of regular AD therapy at follow-up compared to minor allele homozygotes [TT; ultrarapid metabolizers (p = .03)]. Our study suggests that the cumulative consideration of pharmacogenetic risk variants more reliably reflects the impact of the genetic background on depression severity than individual SNPs.

Prevalence, pathological mechanisms, and genetic basis of limb-girdle muscular dystrophies: A review.

Limb-girdle muscular dystrophies (LGMDs) are a highly heterogeneous group of neuromuscular disorders that are associated with weakness and wasting of muscles in legs and arms. Signs and symptoms may begin at any age and usually worsen by time. LGMDs are autosomal disorders with different types and their prevalence is not the same in different areas. New technologies such as next-generation sequencing can accelerate their diagnosis. Several important pathological mechanisms that are involved in the pathology of the LGMD include abnormalities in dystrophin-glycoprotein complex, the sarcomere, glycosylation of dystroglycan, vesicle and molecular trafficking, signal transduction pathways, and nuclear functions. Here, we provide a comprehensive review that integrates LGMD clinical manifestations, prevalence, and some pathological mechanisms involved in LGMDs.

Prevalence of CCR5delta32 in Northeastern Iran.

BACKGROUND: A 32-base pair deletion (∆32) in the open reading frame (ORF) of C-C motif chemokine receptor 5 (CCR5) seems to be a protective variant against immune system diseases, especially human immunodeficiency virus type 1 (HIV-1). We aimed to assess the frequency of CCR5∆32 in the healthy Iranian population. METHODS: In this study, 400 normal samples from Khorasan, northeastern Iran, were randomly selected. The frequency of CCR5∆32 carriers was investigated using PCR analysis. Allele prevalence and the fit to the Hardy-Weinberg equilibrium were analyzed. RESULTS: The prevalence of CCR5∆32 in the northeastern population of Iran was 0.016. Four hundred samples were studied, among which one with CCR5∆32/∆32 and 11 with CCR5Wild/∆32 genotype were detected. CONCLUSION: This study was the first investigation for an assessment of the prevalence of CCR5∆32 in northeastern Iran. The low prevalence of CCR5∆32 allele in the Iranian population may result in the increased susceptibility to HIV-1. In addition, this prevalence is the same as that of reported in East Asia, while is lower than that in the Europeans.

Differences between unipolar mania and bipolar-I disorder: Evidence from nine epidemiological studies.

OBJECTIVES: Although clinical evidence suggests important differences between unipolar mania and bipolar-I disorder (BP-I), epidemiological data are limited. Combining data from nine population-based studies, we compared subjects with mania (M) or mania with mild depression (Md) to those with BP-I with both manic and depressive episodes with respect to demographic and clinical characteristics in order to highlight differences. METHODS: Participants were compared for gender, age, age at onset of mania, psychiatric comorbidity, temperament, and family history of mental disorders. Generalized linear mixed models with adjustment for sex and age as well as for each study source were applied. Analyses were performed for the pooled adult and adolescent samples, separately. RESULTS: Within the included cohorts, 109 adults and 195 adolescents were diagnosed with M/Md and 323 adults and 182 adolescents with BP-I. In both adult and adolescent samples, there was a male preponderance in M/Md, whereas lifetime generalized anxiety and/panic disorders and suicide attempts were less common in M/Md than in BP-I. Furthermore, adults with mania revealed bulimia/binge eating and drug use disorders less frequently than those with BP-I. CONCLUSIONS: The significant differences found in gender and comorbidity between mania and BP-I suggest that unipolar mania, despite its low prevalence, should be established as a separate diagnosis both for clinical and research purposes. In clinical settings, the rarer occurrence of suicide attempts, anxiety, and drug use disorders among individuals with unipolar mania may facilitate successful treatment of the disorder and lead to a more favorable course than that of BP-I disorder.

Therapeutic potential of novel formulated forms of curcumin in the treatment of breast cancer by the targeting of cellular and physiological dysregulated pathways.

Breast cancer is among the most important causes of cancer related death in women. There is a need for novel agents for targeting key signaling pathways to either improve the efficacy of the current therapy, or reduce toxicity. There is some evidence that curcumin may have antitumor activity in breast cancer. Several clinical trials have investigated its activity in patients with breast cancer, including a recent trial in breast cancer patients receiving radiotherapy, in whom it was shown that curcumin reduced the severity of radiation dermatitis, although it is associated with low bioavailability. Several approaches have been developed to increase its absorption rate (e.g., nano crystals, liposomes, polymers, and micelles) and co-delivery of curcumin with adjuvants as well as different conjugation to enhance its bioavailability. In particular, micro-emulsions is an option for transdermal curcumin delivery, which has been reported to increase its absorption. Lipid-based nano-micelles is another approach to enhance curcumin absorption via gastrointestinal tract, while polymer-based nano-formulations (e.g., poly D, L-lactic-co-glycolic [PLGA]) allows the release of curcumin at a sustained level. This review summarizes the current data of the therapeutic potential of novel formulations of curcumin with particular emphasis on recent preclinical and clinical studies in the treatment of breast cancer.