Intrinsically photosensitive retinal ganglion cells: classification, function and clinical implications.

PURPOSE OF REVIEW: The discovery of a new class of intrinsically photosensitive retinal ganglion cells (ipRGCs) revealed their superior role for various nonvisual biological functions, including the pupil light reflex, and circadian photoentrainment. RECENT FINDINGS: Recent works have identified and characterized several anatomically and functionally distinct ipRGC subtypes and have added strong new evidence for the accessory role of ipRGCs in the visual system in humans. SUMMARY: This review summarizes current concepts related to ipRGC morphology, central connections and behavioural functions and highlights recent studies having clinical relevance to ipRGCs. Clinical implications of the melanopsin system are widespread, particularly as related to chronobiology.

Psychological needs of adolescents in the early phase of bipolar disorder: implications for early intervention.

Aim: This paper will describe the rationale for, and importance of, psychological interventions for young people early in the course of bipolar disorder. Methods: Emerging literature in this field will be discussed in addition to describing specific clinical challenges and opportunities with this population. Results: In order to be more developmentally appropriate for young people with bipolar disorder, eight aspects of clinical work which may require modification were identified. Conclusions: The evidence base for the effectiveness of psychological interventions for people diagnosed with bipolar disorder is growing. However, some aspects relating to working with adults with bipolar disorder require modification to be effective in working with young people early in the course of the disorder.

Open to closed system transition traced through the TDIC isotopic signature at the aquifer recharge stage, implications for groundwater 14C dating

14C dating models are limited when considering recent groundwater for which the carbon isotopic signature of the total dissolved inorganic carbon (TDIC) is mainly acquired in the unsaturated zone. Reducing the uncertainties of dating thus implies a better identification of the processes controlling the carbon isotopic composition of the TDIC during groundwater recharge. Geochemical interactions between gas, water and carbonates in the unsaturated zone were investigated for two aquifers (the carbonate-free Fontainebleau sands and carbonate-bearing Astian sands, France) in order to identify the respective roles of CO2 and carbonates on the carbon isotopic signatures of the TDIC; this analysis is usually approached using open or closed system terms. Under fully open system conditions, the seasonality of the 13C values in the soil CO2 can lead to important uncertainties regarding the so-called "initial 14C activity" used in 14C correction models. In a carbonate-bearing unsaturated zone such as in the Astian aquifer, we show that an approach based on fully open or closed system conditions is not appropriate. Although the chemical saturation between water and calcite occurs rapidly within the first metre of the unsaturated zone, the carbon isotopic contents (δ13C) of the CO2 and the TDIC evolve downward, impacted by the dissolution-precipitation of the carbonates. In this study, we propose a numerical approach to describe this evolution. The δ13C and the A 14C (radiocarbon activity) of the TDIC at the base of the carbonate-hearing unsaturated zone depends on (i) the δ13C and the A 14C of the TDIC in the soil determined by the soil CO2, (ii) the water's residence time in the unsaturated zone and (iii) the carbonate precipitation-dissolution fluxes. In this type of situation, the carbonate δ13C-A 14C evolutions indicate the presence of secondary calcite and permit the calculation of its accretion flux, equal to ~ 4.5 ± 0.5 x 10-9 mol grock-1 yr-1. More generally, for other sites under temperate climate and with similar properties to the Astian sands site, this approach allows for a reliable determination of the carbon isotopic composition at the base of the unsaturated zone as the indispensable "input function" data of the carbon cycle into the aquifer.

Implications of diagnosis related groups (DRGs) for the management of hospitals.

Although tremendous advances have been made in the diagnosis and treatment of patients, hospital administrative systems have progressed relatively slowly. The types of information available to managers in industrial sectors are not available in the health sector. For this reason, many phenomena, such as the variations of average costs and lengths of stay between different hospitals, have remained poorly explained.The DRG system defines groups of patients that consume relatively homogeneous quantities of hospital resources. On the basis, it is possible to standardize average lengths of stay and average hospital costs in terms of the differences in case mix treated. Thus DRGs can serve as an explanation of variations in these factors between different hospitals, and also (but not only) for prospective reimbursement schems. As in a number of other European countries, a project has been set up in Switzerland to examine the possibilities of using DRGs in hospital management, planning and financing.

The implications of alternative splicing in the ENCODE protein complement.

Alternative premessenger RNA splicing enables genes to generate more than one gene product. Splicing events that occur within protein coding regions have the potential to alter the biological function of the expressed protein and even to create new protein functions. Alternative splicing has been suggested as one explanation for the discrepancy between the number of human genes and functional complexity. Here, we carry out a detailed study of the alternatively spliced gene products annotated in the ENCODE pilot project. We find that alternative splicing in human genes is more frequent than has commonly been suggested, and we demonstrate that many of the potential alternative gene products will have markedly different structure and function from their constitutively spliced counterparts. For the vast majority of these alternative isoforms, little evidence exists to suggest they have a role as functional proteins, and it seems unlikely that the spectrum of conventional enzymatic or structural functions can be substantially extended through alternative splicing.

Precarious Work: Agenda and Implications for Corporate Social Responsibility

Precarious work, in contrast to regular, permanent wage work, is commonly associated to insecure and unstable, and often poor quality jobs. The concept of precarious work relates either to a socioeconomic group which allows one to refer it to a "class in itself," or as - pursued more recently - to the precarization process which results in a growing fragmentation of societal structures. Common to both conceptions is that they refer to the exposition of workers to employment instability, limited access to legal and union protection, socially irresponsible and discriminating employment practices, and social and economic vulnerability in general. The present contribution provides an overview of some key issues and future directions of research on precarious work relevant to CSR researchers, policy-makers, and social scientists.

The concept of the inflammasome and its rheumatologic implications.

The inflammasome is a proteolytic complex that regulates IL1β and IL-18 secretion in macrophages and dendritic cells. Its plays a vital role in the control of the inflammatory and cellular responses to infectious and danger signals and is an essential part of the innate immune system. Four different inflammasomes have been identified so far, and the NLRP3-inflammasome has been the best-studied in relation to human disease. Activation of the NLRP3-inflammasome by microcrystals, such as monosodium urate (MSU) and basic calcium phosphate (BCP) crystals, leads to IL1β release, which in turn triggers local inflammation. Dysfunction of the NLRP3-inflammasome due to mutations of the NLRP3 gene is the cause of the auto-inflammatory syndrome CAPS. The symptoms and signs of inflammation in both conditions respond to IL1 blockade. IL1 inhibitors have also been used successfully in other idiopathic inflammatory diseases, suggesting that dysregulated inflammasome activity contributes to the pathogenesis of multiple diseases, but the precise underlying mechanisms remain to be identified.

Parental post-traumatic reactions after premature birth: implications for sleeping and eating problems in the infant.

BACKGROUND: Progress in perinatal medicine has made it possible to increase the survival of very or extremely low birthweight infants. Developmental outcomes of surviving preterm infants have been analysed at the paediatric, neurological, cognitive, and behavioural levels, and a series of perinatal and environmental risk factors have been identified. The threat to the child's survival and invasive medical procedures can be very traumatic for the parents. Few empirical reports have considered post-traumatic stress reactions of the parents as a possible variable affecting a child's outcome. Some studies have described sleeping and eating problems as related to prematurity; these problems are especially critical for the parents. OBJECTIVE: To examine the effects of post-traumatic reactions of the parents on sleeping and eating problems of the children. DESIGN: Fifty families with a premature infant (25-33 gestation weeks) and a control group of 25 families with a full term infant participated in the study. Perinatal risks were evaluated during the hospital stay. Mothers and fathers were interviewed when their children were 18 months old about the child's problems and filled in a perinatal post-traumatic stress disorder questionnaire (PPQ). RESULTS: The severity of the perinatal risks only partly predicts a child's problems. Independently of the perinatal risks, the intensity of the post-traumatic reactions of the parents is an important predictor of these problems. CONCLUSIONS: These findings suggest that the parental response to premature birth mediates the risks of later adverse outcomes. Preventive intervention should be promoted.

Psychosocial aspects of cleft lip and palate. Implications for parental education

Lectio praecursoria

Development of the femur - Implications for age and sex determination.

Growth of four variables of the femur (diapyseal length, diaphyseal length plus distal epiphysis, maximum length and vertical diameter of the head) was analyzed by polynomial regression for the purpose of evaluating its significance and capacity for age and sex determination throughout the entire life continuum. Materials included in analysis consisted of 346 specimens ranging from birth to 97 years of age from five documented osteological collections of Western European descent. Linear growth was displayed by each of the four variables. Significant sexual dimorphism was identified in two of the femoral measurements, including maximum length and vertical diameter of the head, from age 15 onward. These results indicate that the two variables may be of use in the determination of sex in sex determination from that age onward. Strong correlation coefficients were identified between femoral size and age for each of the four metric variables. These results indicate that any of the femoral measurements is likely to serve as a useful source to estimate sub-adult age in both archaeological and forensic samples.

ß-Catenin Regulation during the Cell Cycle: Implications in G2/M and Apoptosis

ß-catenin is a multifunctional protein involved in cell-cell adhesion and Wnt signal transduction. ß-Catenin signaling has been proposed to act as inducer of cell proliferation in different tumors. However, in some developmental contexts and cell systems ß-catenin also acts as a positive modulator of apoptosis. To get additional insights into the role of ß-Catenin in the regulation of the cell cycle and apoptosis, we have analyzed the levels and subcellular localization of endogenous ß-catenin and its relation with adenomatous polyposis coli (APC) during the cell cycle in S-phase¿synchronized epithelial cells. ß-Catenin levels increase in S phase, reaching maximum accumulation at late G2/M and then abruptly decreasing as the cells enter into a new G1 phase. In parallel, an increased cytoplasmic and nuclear localization of ß-catenin and APC is observed during S and G2 phases. In addition, strong colocalization of APC with centrosomes, but not ß-catenin, is detected in M phase. Interestingly, overexpression of a stable form of ß-catenin, or inhibition of endogenous ß-catenin degradation, in epidermal keratinocyte cells induces a G2 cell cycle arrest and leads to apoptosis. These results support a role for ß-catenin in the control of cell cycle and apoptosis at G2/M in normal and transformed epidermal keratinocytes.

Rat splanchnic net oxygen consumption. Energetic implications

1. The blood flow, PO2, pH and PCO2 have been estimated in portal and suprahepatic veins as well as in hepatic artery of fed and overnight starved rats given an oral glucose load. From these data the net intestinal, hepatic and splanchnic balances for oxygen and bicarbonate were calculated. The oxygen consumption of the intact animal has also been measured under comparable conditions. 2. The direct utilization of oxygen balances as energy equivalents when establishing the contribution of energy metabolism of liver and intestine to the overall energy expenses of the rat, has been found to be incorrect, since it incorporates the intrinsic error of interorgan proton transfer through bicarbonate. Liver and intestine produced high net bicarbonate balances in all situations tested, implying the elimination (by means of oxidative pathways, i.e. consuming additional oxygen) of high amounts of H+ generated with bicarbonate. The equivalence in energy output of the oxygen balances was then corrected for bicarbonate production to 11-54% lower values. 3. Intestine and liver consume a high proportion of available oxygen, about one-half in basal (fed or starved) conditions and about one-third after gavage, the intestine consumption being about 15% in all situations tested and the liver decreasing its oxygen consumption with gavage.