The acute effects of light on murine sleep during the dark phase: importance of melanopsin for maintenance of light‐induced sleep

Light exerts a direct effect on sleep and wakefulness in nocturnal and diurnal animals, with a light pulse during the dark phase suppressing locomotor activity and promoting sleep in the former. In the present study, we investigated this direct effect of light on various sleep parameters by exposing mice to a broad range of illuminances (0.2–200 μW/cm²; equivalent to 1–1000 lux) for 1 h during the dark phase (zeitgeber time 13–14). Fitting the data with a three‐parameter log model indicated that ～0.1 μW/cm² can generate half the sleep response observed at 200 μW/cm². We observed decreases in total sleep time during the 1 h following the end of the light pulse. Light reduced the latency to sleep from ~30 min in darkness (baseline) to ~10 min at the highest intensity, although this effect was invariant across the light intensities used. We then assessed the role of melanopsin during the rapid transition from wakefulness to sleep at the onset of a light pulse and the maintenance of sleep with a 6‐h 20 μW/cm² light pulse. Even though the melanopsin knockout mice had robust induction of sleep (~35 min) during the first hour of the pulse, it was not maintained. Total sleep decreased by almost 65% by the third hour in comparison with the first hour of the pulse in mice lacking melanopsin, whereas only an 8% decrease was observed in wild‐type mice. Collectively, our findings highlight the selective effects of light on murine sleep, and suggest that melanopsin‐based photoreception is primarily involved in sustaining light‐induced sleep.     

Two independent pathways of regulated necrosis mediate ischemia–reperfusion injury

Regulated necrosis (RN) may result from cyclophilin (Cyp)D-mediated mitochondrial permeability transition (MPT) and receptor-interacting protein kinase (RIPK)1-mediated necroptosis, but it is currently unclear whether there is one common pathway in which CypD and RIPK1 act in or whether separate RN pathways exist. Here, we demonstrate that necroptosis in ischemia–reperfusion injury (IRI) in mice occurs as primary organ damage, independent of the immune system, and that mice deficient for RIPK3, the essential downstream partner of RIPK1 in necroptosis, are protected from IRI. Protection of RIPK3-knockout mice was significantly stronger than of CypD-deficient mice. Mechanistically, in vivo analysis of cisplatin-induced acute kidney injury and hyperacute TNF-shock models in mice suggested the distinctness of CypD-mediated MPT from RIPK1/RIPK3-mediated necroptosis. We, therefore, generated CypD-RIPK3 double-deficient mice that are viable and fertile without an overt phenotype and that survived prolonged IRI, which was lethal to each single knockout. Combined application of the RIPK1 inhibitor necrostatin-1 and the MPT inhibitor sanglifehrin A confirmed the results with mutant mice. The data demonstrate the pathophysiological coexistence and corelevance of two separate pathways of RN in IRI and suggest that combination therapy targeting distinct RN pathways can be beneficial in the treatment of ischemic injury.     

Sesamoid complex disruption as a cause of hallux valgus: Report of three cases

Hallux valgus is perhaps the most common forefoot deformity, usually related to genetic factors, gender and footwear habits. The current cases represent an unusual etiology of the syndrome due to sesamoid ligamentary damage and inter-sesamoid ligament rupture. One of the cases was treated surgically by excision of the non-united lateral sesamoid and reconstruction of the intermetatarsal ligament. Another one was treated by a Wilson-like osteotomy. The third one was conservatively treated by casting. In these cases the hallux valgus angle declined following treatment.     

What do network members know? Network members as reporters of depression among Caucasian-American and African-American older women

Objective: To determine whether family members and friends can be accurate reporters of depression in older women and whether their reports predict diagnostic depression concurrently and across a one-year time interval.

Method: African-American and Caucasian older women (N?=?153; mean age?=?75) previously screened for depression nominated network members (NMs) who could be contacted as informants. NMs completed an informant version of the CES-D, described their closeness to the participant, the extent of the participant's support from family and friends, and their assessment of the participant's typical coping strategies. These reports were then used to predict participant CES-D, Hamilton depression scores, and Structured Clinical Interview (SCID) depression diagnoses concurrently and at six-month and one-year intervals.

Results: NMs’ estimates of participants CES-D status were highly correlated with participants own CES-D scores, and also predicted Hamilton depression scores and SCID diagnoses concurrently and at six months and one year later. NMs’ ratings of participants’ use of positive coping also predicted depression at six months and one year.

Conclusion: NMs knew when elderly women were depressed and their reports were accurate predictors of depression even one year later, which implies that elderly depression does not abate spontaneously. Future research should test the possibility that family and friends might be recruited as allies in encouraging earlier treatment and in providing support to older adults through difficult life transitions.