Partially dead, partially separated: establishing the mechanism between ambiguous loss and grief reaction among caregivers of patients with prolonged disorders of consciousness.

OBJECTIVES:: To trace the psychological mechanism underlying caregivers' emotional experience in prolonged disorders of consciousness, by examining the mediating role of boundary ambiguity in the relationship between ambiguous loss and grief. DESIGN:: Cross-sectional design. SETTING:: The Respiratory Rehabilitation Division of a long-term medical and rehabilitation institute. SUBJECTS:: A total of 64 primary caregivers (69% female) of patients in a vegetative state ( n = 49) or minimally conscious state ( n = 15), with a mean age of 55.5 (SD = 12.3) years. Participants were mostly the patient's children (62%) or partners (27%). The mean caregiving duration was 4.9 (SD = 5.1) years. MAIN MEASURES:: The Boundary Ambiguity Scale, the Revised Need for Closure Scale, an adapted version of the multifactor Two-Track Bereavement Questionnaire, and a sociodemographic questionnaire, which included items regarding caregiving: frequency of visits and perception of the patient's psychological presence. RESULTS:: (1) Caregivers' grief scores (total TTBQ: mean = 2.97; SD = 0.55) did not significantly differ from those exhibited by a normative bereavement sample. (2) Time since injury did not affect caregivers' grief scores (three-year cut-point; P > .05). (3) Mediation analyses revealed that boundary ambiguity (mean = 34.03; SD = 7.55) significantly mediates the relationship between need for closure ( B = .11; confidence interval (CI) = .04-.23) and grief; frequency of visits ( B = .05, CI = .02-.10) and grief and perception of psychological presence ( B = .26, CI = .00-.61) and grief in three separate models. CONCLUSION:: Ambiguity concerning relational boundaries hinders caregivers' ongoing grief reaction and impedes their ability to integrate the loss. High frequency of visits, belief in the patient's psychological presence and difficulties in tolerating uncertainty are all clinical manifestations of caregivers' entangled experience.

The advantage of specific intravenous immunoglobulin (sIVIG) on regular IVIG: experience of the last decade.

During the last decade it has been shown that some components of intravenous immunoglobulin (IVIG) are responsible for their broadly therapeutic application. Currently, such specific subfractions are defined as specific IVIG (sIVIG) and are affinity-purified from commercial IVIGs that target specific antigens/antibodies related to a specific autoimmune disease. A remarkable example of the therapeutic potential of sIVIG is the proven enhanced anti-inflammatory potency of sialylated and recombinant sialylated IVIG obtained from total IVIG. In other experimental models, it has also been demonstrated that sIVIG work in many other contrivances, such as revealing anti-idiotypic networks blocking pathogenic antibodies ameliorating disease activity. sIVIG has also been shown to exert its action by modulating specific receptors expressed on immune cells in both inflammatory and autoimmune diseases. Indeed, sIVIG has emerged as a novel approach to treat different immune-mediated conditions in a more accurate antigen-specific manner. Herein we review experimental evidence supporting sIVIG-efficacy in treating autoimmune diseases and inflammation.

Ornamental plant domestication by aesthetics-driven human cultural niche construction.

Unlike plants that were domesticated to secure food, the domestication and breeding of ornamental plants are driven by aesthetic values. Here, we examine the major elements of the extended evolutionary synthesis (EES) theory that bridges the gap between the biology of ornamental plant domestication and the sociocultural motivations behind it. We propose that it involves specific elements of cumulative cultural evolution (CCE), plant gene-human culture coevolution (PGHCC), and niche construction (NC). Moreover, ornamental plant domestication represents an aesthetics-driven dimension of human niche construction that coevolved with socioeconomic changes and the adoption of new scientific technologies. Initially functioning as symbolic and aesthetic assets, ornamental plants became globally marketed material commodities as a result of the co-dependence of human CCE and prestige-competition motivations.

Linking the salt transcriptome with physiological responses of a salt-resistant Populus species as a strategy to identify genes important for stress acclimation.

To investigate early salt acclimation mechanisms in a salt-tolerant poplar species (Populus euphratica), the kinetics of molecular, metabolic, and physiological changes during a 24-h salt exposure were measured. Three distinct phases of salt stress were identified by analyses of the osmotic pressure and the shoot water potential: dehydration, salt accumulation, and osmotic restoration associated with ionic stress. The duration and intensity of these phases differed between leaves and roots. Transcriptome analysis using P. euphratica-specific microarrays revealed clusters of coexpressed genes in these phases, with only 3% overlapping salt-responsive genes in leaves and roots. Acclimation of cellular metabolism to high salt concentrations involved remodeling of amino acid and protein biosynthesis and increased expression of molecular chaperones (dehydrins, osmotin). Leaves suffered initially from dehydration, which resulted in changes in transcript levels of mitochondrial and photosynthetic genes, indicating adjustment of energy metabolism. Initially, decreases in stress-related genes were found, whereas increases occurred only when leaves had restored the osmotic balance by salt accumulation. Comparative in silico analysis of the poplar stress regulon with Arabidopsis (Arabidopsis thaliana) orthologs was used as a strategy to reduce the number of candidate genes for functional analysis. Analysis of Arabidopsis knockout lines identified a lipocalin-like gene (AtTIL) and a gene encoding a protein with previously unknown functions (AtSIS) to play roles in salt tolerance. In conclusion, by dissecting the stress transcriptome of tolerant species, novel genes important for salt endurance can be identified.

Distinguishing a heart attack from the "broken heart syndrome" (Takotsubo cardiomyopathy).

Takotsubo cardiomyopathy (TC) is a neurocardiological disorder presumed to be triggered by stress, which may cause reversible heart failure, usually in postmenopausal women. It may mimic an acute myocardial infarction, accompanied by minimal elevation of cardiac enzymes, usually without evidence of obstructive coronary artery disease. Most clinicians are unfamiliar with this disorder. Therefore, some TCs are misdiagnosed as acute myocardial infarction. The modified Mayo Clinic criteria usually confirm a diagnosis, although the diagnostic criteria for TC remain controversial. Enhanced awareness by clinicians is important when encountering patients with chest pain and elevated cardiac enzymes. Takotsubo cardiomyopathy is usually associated with a favorable prognosis, although in rare instances it may be associated with life-threatening complications. Supportive care is especially important in the TC management. Our aim was to describe TC, characterize its clinical features, and extensively review the relevant literature.

Promoting Ethically Responsible Use of Agricultural Biotechnology.

Growing global demands for food, bioenergy, and specialty products, along with the threat posed by various environmental changes, present substantial challenges for agricultural production. Agricultural biotechnology offers a promising avenue for meeting these challenges; however, ethical and sociocultural concerns must first be addressed, to ensure widespread public trust and uptake. To be effective, we need to develop solutions that are ethically responsible, socially responsive, relevant to people of different cultural and social backgrounds, and conveyed to the public in a convincing and straightforward manner. Here, we highlight how ethical approaches, principled decision-making strategies, citizen-stakeholder participation, effective science communication, and bioethics education should be used to guide responsible use of agricultural biotechnology.

Vitamin D insufficiency in a sunny environment: a demographic and seasonal analysis.

BACKGROUND: Hypovitaminosis D has been shown to be extremely common in various regions around the world, mostly at high latitudes. Israel is characterized by certain features--cultural (e.g., ethnic isolates) and geographic (e.g., sunny climate)--that have been identified for their possible association with vitamin D status. OBJECTIVES: To conduct an ecological study on a representative sample of the population of Israel, testing vitamin D status across age groups, genders, ethnic groups, and seasons. METHODS: We obtained serum samples from 195 heaIthy Israeli volunteers representing a broad demographic spectrum. Serum concentrations of 25(OH)D were measured with the commercial kit Liaison 25(OH)D Assay (DiaSorin, Italy). RESULTS: The mean vitamin D level for the entire cohort was surprisingly low (22.9 +/- 10.1 ng/ml), with 149 subjects (78%) suffering from vitamin D insufficiency (< 30 ng/lml). Vitamin D status was better in infants than in olderage groups. Differences by gender were significant only inthe infant age group (i.e., vitamin D status was worse among females) and were not prominent across older ages. Israelis of Ashkenazi origin had higher vitamin D mean levels than those of Sephardic origin, who, in turn, had higher vitamin D levels than Arab subjects (31.4 +/- 12, 24.1 +/- 10, and 17.6 +/- 9 ng/ml respectively). With regard to season, there were no differences between the samples collected in winter and the samples collected in summer. CONCLUSIONS: The results suggest that hypovitaminosis D is common across all ages, genders and seasons in Israel, a country characterized by a sunny Mediterranean climate. Specific ethnic groups may be at especially high risk.

[Acute respiratory distress syndrome (ARDS) as a complication of malaria P.vivax].

The authors review a case of an Indian tourist couple both presenting a clinical picture of intermittent fever, thrombocytopenia and relative leukopenia several days after their arrival to israel. The diagnosis of Plasmodium vivax (P.vivax) malaria was established in both patients and antimalarial treatment with chloroquine was initiated. Shortly after initiating the treatment, the husband developed clinical acute respiratory distress syndrome (ARDS). With symptomatic treatment, the patient recovered within few days. The diagnosis of P. vivax was confirmed by PCR, and was shown to be a single infection with no Plasmodium falciparum as co-infection. Although P. vivax is considered as having a benign course, in contrast to P. falciparum infections, in recent years there have been an increased number of reports of complicated P. vivax malaria, mainly ARDS. Physicians should be aware of the possible complicated course of P. vivax malaria.

[The effect of blocking TNF-alpha in patients with cancer-related cachexia and anorexia].

Cancer-related cachexia and anorexia are present in more than 80% of patients with malignancies. The pathophysiology is not fully known and during the past several years major attention was attributed to the function of secreted cytokines, such as TNF-alpha, as a fundamental part of the process. In the attempt to prevent the weight loss, which in many cases causes the patients' death, many studies have been conducted where the effect of the cytokine TNF-alpha was blocked. This article presents two different studies from the past several years where the effect was inhibited by two different methods: one by the monoclonal antibody Infliximab and the other by blocking the TNF-alpha receptor with Etanercept. Both were double-blinded and the patients were randomly divided into arms, with the control group treated with placebo. In both groups, primary and secondary outcomes were defined, however, in the end, no statistical significance was achieved. In conclusion, cancer-related cachexia and anorexia are not the result of one cytokine by itself and blocking it causes only a minimal change without any statistical significance in cancer patients. It is reasonable to assume that the body adaptation to the tumor, which results in cachexia, is due to several mediators working together rather than a single major mediator.

[The clinical importance of anti-ribosomal-P antibodies].

Anti-ribosomal phosphoprotein autoantibodies (anti-RP Abs) are highly specific for SLE, especially for neuropsychiatric manifestations including psychosis, mood disorders, anxiety, cognitive dysfunction and delirium. In addition to the neuropsychiatric involvement, anti-RP antibodies are believed to be correlated with nephritis, hepatitis and dermal diseases in SLE. Several studies indicate the association between increased titers of anti-RP Abs in the patient's sera and active SLE disease. The reported prevalence of anti-RP Abs among SLE patients is 10%-40%. Recently, a connection between the presence of anti-RP Abs in the serum and class V lupus nephritis has been demonstrated. Anti-RP Abs binds 3 ribosomal proteins identified as P0, P1 and P2 (38, 19 and 17-kDa, respectively) by recognizing a certain epitope found in those 3 proteins. This specific epitope contains 22 amino acids at the C terminal end (C-22) of the protein. There are studies in the literature relating to the involvement of anti-RP Abs in the pathogenesis of organ damage. The main pathways described are cross-reaction with anti-dsDNA antibodies, a cytotoxic effect on mesangium cell proliferation, invasion into living cells and onset of apoptosis, a defect in the synthesis of apolipoprotein B resulting in accumulation of lipids inside the cell, and downregulation of the total protein synthesis. The authors provide an updated review concerning the multisystem involvement of anti-RP Abs in SLE, particularly in the brain, kidney and liver. Moreover, this article includes a summary of the most relevant studies regarding the cellular involvement of anti-RP Abs.

[Paget's disease and hypercalcemia: coincidence or causal relationship?].

Paget's disease is a chronic disease in which osteoclast mediated bone resorption precedes imperfect osteoblast mediated bone repair. Symptoms include bone pain, pathological fractures, osteoarthritis and neurological symptoms. There is evidence that genetic and viral component are involved in the etiology. Hypercalcemia is rare and when it is diagnosed, primary hyperparathyroidism should be ruled out. The authors present a patient with Paget's disease and concomitant hypercalcemia. Evaluation for hypercalcemia revealed an adenoma of the parathyroid. However, despite the removal of the adenoma, the symptoms persisted. Previous studies showed that hyperparathyroidism causes hypercalcemia in Paget's disease patients. Removal of the adenoma led to improvement in calcium and alkaline phosphatase (ALP) levels but clinical improvement is seen only in patients with high calcium level prior to the operation. This leads to the assumption that symptoms of Paget's disease are due to osteoclast hypersensitivity to parathyroid hormone (PTH) and by removing the adenoma the osteoclast activity is also reduced. In summary, the most common cause of hypercalcemia in Paget's disease patients is hyperparathyroidism and adenectomy may improve the biochemical and sometimes also the clinical symptoms of Paget's disease.

Accelerating Climate Resilient Plant Breeding by Applying Next-Generation Artificial Intelligence.

Breeding crops for high yield and superior adaptability to new and variable climates is imperative to ensure continued food security, biomass production, and ecosystem services. Advances in genomics and phenomics are delivering insights into the complex biological mechanisms that underlie plant functions in response to environmental perturbations. However, linking genotype to phenotype remains a huge challenge and is hampering the optimal application of high-throughput genomics and phenomics to advanced breeding. Critical to success is the need to assimilate large amounts of data into biologically meaningful interpretations. Here, we present the current state of genomics and field phenomics, explore emerging approaches and challenges for multiomics big data integration by means of next-generation (Next-Gen) artificial intelligence (AI), and propose a workable path to improvement.

Coexistence of the antiphospholipid syndrome and abdominal aortic aneurysm.

The antiphospholipid syndrome is characterized by recurrent fetal loss, venous and/or arterial thrombosis, and thrombocytopenia associated with elevated titers of lupus anticoagulant and anticardiolipin antibodies. Although thrombosis is the characteristic vascular involvement in APS, the development of vascular aneurysms in patients with APS has been reported. We describe four patients with established APS who developed abdominal aortic aneurysm, and review the literature on previous published cases of arterial aneurysms developing in patients with APS. In addition, we discuss the possible pathophysiological association between APS and the development of this vascular abnormality.

[The approach to recurrent infections with Clostridium difficile].

Clostridium difficile associated diarrhea is one of the most common nosocomial infections. This infection is solely induced by antibiotic treatment. The risk for this disease increased with the length of hospital admission, the specific type of antibiotic, the patient age and associated co-morbidities. Most patients respond to the antibiotic treatment with Vancomycin or Metronidazole. Unfortunately, in 15-25% of patients this disease will recur. The approach to recurrent and refractory disease requires creativity, combining antibiotics with other complementary methods. This includes: different combinations of antibiotic, anion binding resins, probiotics, fecal brachytherapy and IVIg.

Multiple display of catalytic modules on a protein scaffold: nano-fabrication of enzyme particles.

Self assembly is a prerequisite for fabricating nanoscale structures. Here we present a new fusion protein based on the stress-responsive homo-oligomeric protein, SP1. This ring-shaped protein is a highly stable homododecamer, which can be potentially utilized to self-assemble different modules and enzymes in a predicted and oriented manner. For that purpose, a cohesin module (a component of the bacterial cellulosome) was selected, its gene fused in-frame to SP1, and the fusion protein was expressed in Escherichia coli. The cohesin module, specialized to incorporate different enzymes through specific recognition of a dockerin modular counterpart, is used to display new moieties on the SP1 scaffold. The SP1 scaffold displayed 12 active cohesin modules and specific binding to a dockerin-fused cellulase enzyme from Thermobifida fusca. Moreover, we found a significant increase in specific activity of the scaffold-displayed enzymes.

Colchicine-induced rhabdomyolysis.

A case of colchicine-induced rhabdomyolysis is reported. A 79-year-old man with ischemic heart disease, chronic atrial fibrillation, chronic renal failure, hypothyroidism, and gout arthritis was hospitalized because of fatigue, myalgia, and leg weakness, shortly after starting treatment with colchicine. Investigation confirmed the diagnosis of rhabdomyolysis, and discontinuation of colchicine resulted in resolution of clinical and biochemical features of rhabdomylysis. Colchicine-induced rhabdomyolysis is a rare complication, and the postulated mechanisms and risk factors for this severe complication are discussed.

Recent advances in engineering plant tolerance to abiotic stress: achievements and limitations.

Abiotic stresses, especially salinity and drought, are the primary causes of crop loss worldwide. Plant adaptation to environmental stresses is dependent upon the activation of cascades of molecular networks involved in stress perception, signal transduction, and the expression of specific stress-related genes and metabolites. Consequently, engineering genes that protect and maintain the function and structure of cellular components can enhance tolerance to stress. Our limited knowledge of stress-associated metabolism remains a major gap in our understanding; therefore, comprehensive profiling of stress-associated metabolites is most relevant to the successful molecular breeding of stress-tolerant crop plants. Unraveling additional stress-associated gene resources, from both crop plants and highly salt- and drought-tolerant model plants, will enable future molecular dissection of salt-tolerance mechanisms in important crop plants.

Antioxidant activities and anthocyanin content of fresh fruits of common fig (Ficus carica L.).

Fig fruit has been a typical component in the health-promoting Mediterranean diet for millennia. To study the potential health-promoting constituents of fig fruits, six commercial fig varieties differing in color (black, red, yellow, and green) were analyzed for total polyphenols, total flavonoids, antioxidant capacity, and amount and profile of anthocyanins. Using reversed-phase liquid chromatography (RP-LC), various concentrations of anthocyanins but a similar profile was found in all varieties studied. Hydrolysis revealed cyanidin as the major aglycon. Proton and carbon NMR confirmed cyanidin-3-O-rhamnoglucoside (cyanidin-3-O-rutinoside; C3R) as the main anthocyanin in all fruits. Color appearance of fig extract correlated well with total polyphenols, flavonoids, anthocyanins, and antioxidant capacity. Extracts of darker varieties showed higher contents of phytochemicals compared to lighter colored varieties. Fruit skins contributed most of the above phytochemicals and antioxidant activity compared to the fruit pulp. Antioxidant capacity correlated well with the amounts of polyphenols and anthocyanins (R2 = 0.985 and 0.992, respectively). In the dark-colored Mission and the red Brown-Turkey varieties, the anthocyanin fraction contributed 36 and 28% of the total antioxidant capacity, respectively. C3R contributed 92% of the total antioxidant capacity of the anthocyanin fraction. Fruits of the Mission variety contained the highest levels of polyphenols, flavonoids, and anthocyanins and exhibited the highest antioxidant capacity.

CEACAM1 and MICA as novel serum biomarkers in patients with acute and recurrent pericarditis.

BACKGROUND: The immune response plays a significant role in pericarditis, but the mechanisms of disease are poorly defined. Further, efficient monitoring and predictive clinical tools are unavailable. Carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1) is an immune-inhibitory protein, while MHC class I chain related protein A (MICA) and B (MICB) have an immune-stimulating function. METHODS AND RESULTS: Serum CEACAM1, MICA and MICB concentrations were measured by ELISA in ~50 subjects of each group: acute pericarditis (AP), recurrent pericarditis (RP) and lupus (SLE) patients, metastatic melanoma patients as well as healthy donors. Serum CEACAM1 was dramatically elevated in AP and RP patients, but not in SLE patients, and displayed a highly accurate profile in ROC curve analyses. MICA and MICB were elevated in some pericarditis patients. All markers were enhanced in metastatic melanoma patients irrespective of neoplastic pericardial involvement. Etiology-guided analysis of RP patients showed that very low MICA levels were associated with idiopathic RP, while high MICA was associated with autoimmune and post-operative RP. Importantly, MICA was significantly associated with recurrences, independently of other potentially confounding parameters such as age, time of follow up or treatment modality. CONCLUSIONS: Here we report for the first time on CEACAM1 as a potentially novel biomarker for pericarditis, as well as on MICA as an innovative prognostic marker in these patients. Determination of the roles of these immune factors, as well as their diagnostic and prognostic values should be determined in future prospective studies.