Photobiomodulation in the infrared spectrum reverses the expansion of circulating natural killer cells and brain microglial activation in Sanfilippo mice.

Sanfilippo syndrome results from inherited mutations in genes encoding lysosomal enzymes that catabolise heparan sulfate (HS), leading to early childhood-onset neurodegeneration. This study explores the therapeutic potential of photobiomodulation (PBM), which is neuroprotective and anti-inflammatory in several neurodegenerative diseases; it is also safe and PBM devices are readily available. We investigated the effects of 10-14 days transcranial PBM at 670 nm (2 or 4 J/cm2/day) or 904 nm (4 J/cm2/day) in young (3 weeks) and older (15 weeks) Sanfilippo or mucopolysaccharidosis type IIIA (MPS IIIA) mice. Although we found no PBM-induced changes in HS accumulation, astrocyte activation, CD206 (an anti-inflammatory marker) and BDNF expression in the brains of Sanfilippo mice, there was a near-normalisation of microglial activation in older MPS IIIA mice by 904 nm PBM, with decreased IBA1 expression and a return of their morphology towards a resting state. Immune cell immunophenotyping of peripheral blood with mass cytometry revealed increased pro-inflammatory signalling through pSTAT1 and p-p38 in NK and T cells in young but not older MPS IIIA mice (5 weeks of age), and expansion of NK, B and CD8+ T cells in older affected mice (17 weeks of age), highlighting the importance of innate and adaptive lymphocytes in Sanfilippo syndrome. Notably, 670 and 904 nm PBM both reversed the Sanfilippo-induced increase in pSTAT1 and p-p38 expression in multiple leukocyte populations in young mice, while 904 nm reversed the increase in NK cells in older mice. In conclusion, this is the first study to demonstrate the beneficial effects of PBM in Sanfilippo mice. The distinct reduction in microglial activation and NK cell pro-inflammatory signalling and number suggests PBM may alleviate neuroinflammation and lymphocyte activation, encouraging further investigation of PBM as a standalone, or complementary therapy in Sanfilippo syndrome.

Leukemic stem cells: a review.

A small subset of cells in a patient with leukemia, termed leukemic stem cells (LSCs) have been shown to be responsible for the proliferation of disease. LSCs are thought to derive from normal hematopoietic stem cells, but are phenotypically distinguishable in that they are CD90(-), CD117(-), and CD123(+). Research in mouse models provides several potential therapeutics to target these cells in human patients. Eliminating LSCs should provide an efficient, potentially curative treatment option for leukemia patients.

An exploration of nursing documentation of pressure ulcer care in an acute setting in Ireland.

OBJECTIVE: To explore the nature and quality of documented care planning for pressure ulcers in a large teaching hospital in the Republic of Ireland. METHOD: A mixed method design was used; this encompassed a descriptive survey that retrospectively evaluated nursing records (n=85) in two wards (orthopaedic and care of the older adult) and a focus group (n=13) that explored nurses' perspectives of the factors influencing concordance and the quality of nursing documentation. Only records of at-risk patients (Waterlow score of >10) were included. RESULTS: It was identified that 47% (n=40) were assessed as at high or very high risk of developing a pressure ulcer. Fifty-two patients (61%) had a weekly risk assessment, but 25% (n=21) had only one follow-up assessment. Only 45% (n=38) of charts had some evidence of documented care planning, and of those 53% (n=20) had no evidence of implementation of the care plan and 66% (n=25) had no evidence of outcome evaluation. Only 48% (n=41) of this at-risk population was nutritionally assessed. Of patients admitted with and without a pressure ulcer, there was no record of regular positioning in 70% (n=59) and 60% (n=51) respectively. CONCLUSION: Documentation on pressure ulcer care is not standardised and requires development. CONFLICT OF INTEREST: None.

Long-term histologic and mechanical results of a Permacol™ abdominal wall explant.

PURPOSE: We hypothesize that Permacol™ may allow controlled integration over time while providing long-term mechanical stability and native tissue remodeling. The purpose of this report is to investigate these properties in an explanted piece of Permacol™ after 2 years in vivo. METHODS: A 62-year-old female presented with a complex abdominal wall history having undergone a transverse rectus abdominis musculocutaneous (TRAM) flap breast reconstruction 10 years ago, followed by an abdominal wall repair with Marlex™ mesh for weakness 3 years later. Two years ago, she developed an abdominal bulge repaired with a Permacol™ overlay. Twenty-three months postoperatively, she presented with abdominal distension. Computed tomography (CT) scanning demonstrated a fluid collection behind the Permacol™. She underwent incision and drainage of the hematoma/bursa and quilting repair of the abdominal wall. A 1 × 6-cm Permacol™ section was resected as part of closure. Histology, immunohistochemistry, and mechanical testing of the Permacol™ explant were performed. RESULTS: Histology showed fibroblast and blood vessel ingrowth with no cellular infiltrates reflective of inflammation. Immunohistochemistry for human-specific collagen types I and III and elastin detected staining throughout. Sections stained with non-specific control antibody exhibited no discernable staining. Elastin highlighted blood vessels. Native Permacol™ had a breaking strength of ~20 N, while for explanted Permacol™, it was ~33 N. CONCLUSIONS: Permacol™ maintained durability while allowing vascular ingrowth without residual inflammation. Explant demonstrated integration with human collagen and elastin remodeling throughout. Increase in mechanical strength may reflect newly synthesized collagen and elastin. These histologic findings and clinical result support the use of Permacol™ in complex abdominal wall reconstruction.

Interrupted vs. uninterrupted training on BMD during growth.

This study compared a resistance training program where the exercise was uninterrupted (UT, i.e., continuous repetitions) against a resistance training program where the exercise was interrupted (IT, i.e., 3 exercise sessions during a training day) for enhancing bone modeling and bone mineral density (BMD) in maturating animals. The total volume of work performed between the two resistance training programs was equivalent by design. 24 young male rats were randomly divided into Control (Con, n = 8), UT (n = 8) and IT (n = 8) resistance trained groups. The UT and IT groups were conditioned to climb a vertical ladder with weights appended to their tail 3 days/wk for 6 wks. After the 6-wk program, serum osteocalcin was not significantly different between groups, whereas the adjusted urinary deoxypyridinoline (DPD) was significantly lower for both UT (81.03 +/- 5.53) and IT (88.30 +/- 7.29) compared to Con (128.13 +/- 9.99). Tibial BMD (assessed via DXA) was significantly greater for UT (0.222 +/- 0.005 g/cm (2)) and IT (0.219 +/- 0.003 g/cm (2)) when compared to Con (0.205 +/- 0.004 g/cm (2)). There was no significant difference in DPD or BMD between UT and IT groups. The results indicate that both interrupted and continuous, uninterrupted resistance training programs were equally effective in stimulating bone modeling.

Resistance training and bone mineral density during growth.

This study examined the efficacy of two different resistance training programs in enhancing bone modeling and bone mineral density (BMD) in maturating rats. One exercise mode involved lifting a lighter weight with more repetitions (LI), while the other regimen involved lifting a heavier weight with fewer repetitions (HI) where the total volume of work between exercise programs was equivalent by design. Twenty-three male rats were randomly divided into control (Con, n = 8), LI (n = 7), and HI (n = 8) groups. The LI and HI groups were conditioned to climb a vertical ladder with weights appended to their tail 4 days/wk for 6 wks. After training, serum osteocalcin (OC) was significantly (p < 0.05) higher in both HI (45.2 +/- 1.7 ng/ml) and LI (39.1 +/- 2.2 ng/ml) when compared to Con (29.9 +/- 0.9 ng/ml). Left tibial BMD was significantly (p < 0.05) greater for HI (0.231 +/- 0.004 g/cm (2)) when compared to both LI (0.213 +/- 0.003 g/cm (2)) and Con (0.206 +/- 0.005 g/cm (2)) with no significant difference between LI and Con. The results indicate that both HI and LI are effective in elevating serum OC, implicating an osteogenic response; however, only HI resulted in a significant elevation in BMD.

Economic evaluation of therapeutic interventions to prevent Type 2 diabetes in Canada.

AIMS: To compare the health and economic outcomes of using acarbose, an intensive lifestyle modification programme, metformin or no intervention to prevent progression to diabetes in Canadian individuals with impaired glucose tolerance (IGT). METHODS: A model was developed to simulate the course of individuals with IGT under each treatment strategy. Patients remain in the IGT state or transition from IGT to diabetes, to normal glucose tolerance (NGT) or to death. Effectiveness and resource use data were derived from published intervention trials. A comprehensive health-care payer perspective incorporating all major direct costs, reported in 2000 Canadian dollars, was adopted. RESULTS: Over a decade, 70 of the 1000 untreated patients are expected to die and 542 develop diabetes. Intensive lifestyle modification is estimated to prevent 117 cases of diabetes, while metformin would prevent 52 and acarbose 74 cases. The proportion of those who return to NGT also increases with any treatment. While lifestyle modification is more effective, it can increase overall costs depending on how it is implemented, whereas acarbose and metformin reduce costs by nearly $1000 per patient. Lifestyle modification was cost effective, varying from CAD $10 000/LYG vs. acarbose. Acarbose costs somewhat more than metformin, but is more effective: CAD $1798/LYG. CONCLUSION: The results of this model suggest that the treatment of IGT in Canada is a cost-effective way to prevent diabetes and may generate savings. While pharmacological treatments tended to be less costly, intensive lifestyle modification, if maintained, led to the greatest health benefits at reasonable incremental costs.

Expression of mCLOCK and other circadian clock-relevant proteins in the mouse suprachiasmatic nuclei.

Circadian timing in mammals is based upon the cell-autonomous clockwork located in the suprachiasmatic nuclei (SCN) of the hypothalamus. It is thought to involve interlocked feedback loops in which periodic transcriptional drive to core clock genes is mediated by CLOCK/BMAL1 heterodimers. Negative-feedback actions of the encoded proteins PER and CRY terminate this phase of the cycle. In lower species, rhythmic abundance of the mCLOCK homologue initiates the subsequent cycle. By contrast, it is proposed that the new circadian cycle in mammals is triggered by indirect, positive transcriptional actions leading to a subsequent surge in BMAL1. The aim of this study was to test predictions made by this model concerning the behaviour of the native clock factor mCLOCK in the mouse SCN. Using in situ hybridization, immunocytochemistry, Western blotting and immunoprecipitation, we demonstrate constitutive expression of mCLOCK as a nuclear antigen in the SCN. mCLOCK forms alternating, periodic associations with either mBMAL1 or the negative regulators mPER and mCRY. The results confirm predictions made by the "two-loop" model of the mouse clock, and further highlight the role of interlocked cycles of positive and negative transcriptional regulatory complexes at the heart of the circadian clockwork.

Utilization of health care services by patients with chronic obstructive pulmonary disease.

In order to identify healthcare resource use patterns associated with chronic obstructive pulmonary disease (COPD), resource utilization (RU) data collection was integrated into a randomized, double-blind placebo-controlled study of Viozan (sibenadet HCl). This study enrolled patients with symptomatic, smoking-related COPD, randomized to receive sibenadet or placebo for a 52-week treatment period. A questionnaire establishing typical pre-trial, COPD-related RU was completed by each patient. Subsequent data were collected by means of an Interactive Voice Response System (IVRS) at 30-day intervals (14 time points) during the study and in the follow-up period. The IVRS system facilitated data collection and minimized inconvenience to the patient. Compliance with the requirement to record details of the healthcare services during the year-long study was high. No overall trend for lower RU was associated with sibenadet therapy, which correlates with the lack of sustained clinical effect seen in studies conducted concurrently. These data do, however, provide valuable information on RU associated with COPD and insights into adjustments associated with changes in disease course. Physicians were seen to be the most common source of care for patients with COPD and more of the patients with severe COPD (stage III) than mild (stage I) were seen to utilize the most expensive resources (e.g. inpatient hospital care). For those patients who experienced an exacerbation during the trial (irrespective of treatment group), resource use was increased during the periods when an exacerbation was reported when compared with the periods before or after an exacerbation. The proportion of cases attending the physician doubled and with a trip to the Emergency Room (ER) increased approximately ninefold during the reporting period in which the exacerbation occurred compared with the previous month. This study has shown that use of an IVRS, even in elderly patients, is an effective means of gathering RU data over long periods. The study findings suggest that the advent of effective therapeutic interventions, particularly any with the ability to minimize exacerbations and limit disease progression, could impact on the health care services used and potentially reduce associated costs.

Diabetes in Canada: direct medical costs of major macrovascular complications.

OBJECTIVES: To estimate direct medical costs of managing major macrovascular complications in diabetic patients. METHODS: Costs were estimated for acute myocardial infarction (AMI) and ischemic stroke by applying unit costs to typical resource use profiles. Data were obtained from many Canadian sources, including the Ontario Case Cost Project, provincial physician and laboratory fee schedules, provincial formularies, government reports, and peer-reviewed literature. For each complication, the event costs per patient are those associated with resource use specific to the acute episode and any subsequent care occurring in the first year. State costs are the annual costs per patient of continued management. All costs are expressed in 1996 Canadian dollars. RESULTS: Acute hospital care accounts for approximately half of the first year management costs ($15,125) of AMI. Given the greater need for postacute care, acute hospital care has less impact (28%) on event costs for stroke ($31,076). The state costs for AMI and stroke are $1544 and $8141 per patient, respectively. CONCLUSIONS: Macrovascular complications of diabetes potentially represent a substantial burden to Canada's health care system. As new therapies emerge that may reduce the incidence of some diabetic complications, decision makers will need information to make critical decisions regarding how to spend limited health care dollars. Published literature lacks Canadian-specific cost estimates that may be readily translated into patient-level cost inputs for an economic model. This paper provides two key pieces of the many needed to understand the scope of the economic burden of diabetes and its complications for Canada.

Modifications to the hand-held Gene Gun: improvements for in vitro biolistic transfection of organotypic neuronal tissue.

Transfection and subsequent expression of DNA in living neuronal tissue is problematic and no technique has emerged that is completely non-damaging, efficient and reproducible. The Bio-Rad hand-held Gene Gun has overcome some of these problems by exploiting a biolistic method in which small gold particles carrying plasmid DNA are propelled into neurons whilst causing minimal detectable cell damage. In its current configuration, however, the Bio-Rad Gene Gun is optimised for transfecting cells in dispersed cultures, and therefore delivers particles superficially over a relatively wide area. Here we report modifications to the Bio-Rad Gene Gun that both enhance its accuracy by restricting its target area, and increase the depth penetration achieved by gold particles, thereby allowing smaller and deeper tissues to be transfected. These alterations make the modified Gene Gun more applicable for in vitro transfection of organotypic cultures and enhance its potential utility for in vivo gene delivery. Moreover, the modified configuration operates successfully at lower gas pressures, thereby reducing even further the degree of cell damage incurred during transfection.

The nonuniform distribution of the GABA(A) receptor alpha 1 subunit influences inhibitory synaptic transmission to motoneurons within a motor nucleus.

Using immunohistochemistry we studied the distribution of GABA(A) and glycine receptor alpha1 subunits in the rat hypoglossal nucleus during postnatal development. In the neonate [postnatal day (P) 1-3] and adult nucleus (P28-30), GABA(A) receptor alpha1 subunit labeling was relatively modest. However, in the juvenile nucleus (P9-13), labeling was strong in the ventrolateral region and moderate in the dorsal region. Glycine receptor alpha1 subunit labeling was strong and uniform in the juvenile and adult nucleus and absent in the neonate nucleus. GABA and glycine neurotransmitter labeling was uniform throughout the neonatal and juvenile nucleus. To study the functional consequences of this regional differential GABA(A) receptor alpha1 subunit distribution, we voltage clamped juvenile hypoglossal motoneurons (HMs) from the ventrolateral and dorsal regions and recorded spontaneous miniature IPSCs (mIPSCs). Pure GABAergic events had slower decay times than glycinergic events. Although pure GABAergic and glycinergic decay times did not differ depending on HM location, the decays of mixed mIPSCs from ventrolateral HMs, recorded without GABA(A) and glycine receptor antagonists, had significantly slower decays than mIPSCs from dorsal HMs. Focally applied GABA and glycine onto outside-out patches revealed that the GABAergic to glycinergic peak current amplitude ratio was larger for patches from ventrolateral HMs compared with dorsal HMs. Dual component mIPSCs, presumably caused by co-release of GABA and glycine, were recorded more frequently in the ventrolateral nucleus. These data suggest that the number of synapses using GABA(A) receptor-mediated transmission is greater on ventrolateral HMs than dorsal HMs, demonstrating a nonuniformity of synaptic function within a defined motor nucleus.

Economic analysis of initial HIV treatment. Efavirenz- versus indinavir-containing triple therapy.

OBJECTIVE: To compare the clinical and economic outcomes associated with triple therapy containing efavirenz or indinavir and 2 nucleoside reverse transcriptase inhibitors (NRTIs; zidovudine and lamivudine) in HIV-positive patients. DESIGN AND SETTING: An economic model based on viral load and CD4+ cell counts to predict long term outcomes such as progression to AIDS and AIDS-related death was developed and then analysed using data from a randomised clinical trial. Cost estimates from the healthcare system perspective were based on data from 6 state, all-payor databases, the AIDS Cost and Services Utilisation Study, and other literature. Analyses were carried out for time horizons between 5 and 15 years. PATIENTS AND INTERVENTIONS: HIV-positive patients with limited exposure to NRTIs. Initial regimens consisted of efavirenz or indinavir, each combined with 2 NRTIs. A maximum of 2 switches to other regimens was permitted. MAIN OUTCOME MEASURES AND RESULTS: The efavirenz-containing triple therapy regimen was predicted to prolong survival at a savings of up to 10,923 US dollars (1998 values) relative to initial therapy with the indinavir-containing regimen. Patients who receive efavirenz are expected to have 11% greater survival at 5 years and fewer treatment failures (28 vs 52%, at 2 years). Overall, the economic and health benefits predicted for the efavirenz-containing regimen were robust to reasonable variation in key parameters. CONCLUSIONS: The superior clinical trial outcomes for efavirenz-containing regimens should translate into substantial economic and health benefits.

Intracellular pathways regulating ciliary beating of rat brain ependymal cells.

1. The mammalian brain ventricles are lined with ciliated ependymal cells. As yet little is known about the mechanisms by which neurotransmitters regulate cilia beat frequency (CBF). 2. Application of 5-HT to ependymal cells in cultured rat brainstem slices caused CBF to increase. 5-HT had an EC50 of 30 microM and at 100 microM attained a near-maximal CBF increase of 52.7 +/- 4.1 % (mean +/- s.d.) (n = 8). 3. Bathing slices in Ca2+-free solution markedly reduced the 5-HT-mediated increase in CBF. Fluorescence measurements revealed that 5-HT caused a marked transient elevation in cytosolic Ca2+ ([Ca2+]c) that then slowly decreased to a plateau level. Analysis showed that the [Ca2+]c transient was due to release of Ca2+ from inositol 1,4,5-trisphosphate (IP3)-sensitive stores; the plateau was probably due to extracellular Ca2+ influx through Ca2+ release-activated Ca2+ (CRAC) channels. 4. Application of ATP caused a sustained decrease in CBF. ATP had an EC50 of about 50 microM and 100 microM ATP resulted in a maximal 57.5 +/- 6.5 % (n = 12) decrease in CBF. The ATP-induced decrease in CBF was unaffected by lowering extracellular [Ca2+], and no changes in [Ca2+]c were observed. Exposure of ependymal cells to forskolin caused a decrease in CBF. Ciliated ependymal cells loaded with caged cAMP exhibited a 54.3 +/- 7.5 % (n = 9) decrease in CBF following uncaging. These results suggest that ATP reduces CBF by a Ca2+-independent cAMP-mediated pathway. 5. Application of 5-HT and adenosine-5'-O-3-thiotriphosphate (ATP-gamma-S) to acutely isolated ciliated ependymal cells resulted in CBF responses similar to those of ependymal cells in cultured slices suggesting that these neurotransmitters act directly on these cells. 6. The opposite response of ciliated ependymal cells to 5-HT and ATP provides a novel mechanism for their active involvement in central nervous system signalling.

Alzheimer's disease and other dementia in nursing homes: levels of management and cost.

OBJECTIVE: To estimate comparative management levels and the annual cost of caring for a nursing home resident with and without dementia. METHOD: Data from the 1995 Massachusetts Medicaid nursing home database were used to examine residents with Alzheimer's disease, other types of dementia, and no dementia to determine care and dependency levels. Massachusetts Medicaid 1997 per-diem rates for each of 10 designated management levels were applied accordingly to residents in each level to estimate annual care costs. Costs from this analysis are reported in 1997 U.S. dollars. RESULTS: Of the 49,724 nursing home residents identified, 26.4% had a documented diagnosis of dementia. On average, a resident with dementia requires 229 more hours of care annually than one without dementia, resulting in a mean additional cost of $3,865 per patient with dementia per year. CONCLUSIONS: Dementia increases the care needs and cost of caring for a nursing home resident.

Factors affecting survival after prehospital asystolic cardiac arrest in a Basic Life Support-Defibrillation system.

OBJECTIVES: Previous studies have shown a low but meaningful survival rate in cases of prehospital cardiac arrest with an initial rhythm of asystole. There may be, however, an identifiable subgroup in which resuscitation efforts are futile. This study identified potential field criteria for predicting 100% nonsurvival when the presenting rhythm is asystole in a Basic Life Support-Defibrillation (BLS-D) system. METHODS: This prospective cohort study, a component of Phases I and II of the Ontario Prehospital Advanced Life Support (OPALS) Study, was conducted in 21 Ontario communities with BLS-D level of care, and included all adult arrests of presumed cardiac etiology according to the Utstein Style Guidelines. Analyses included descriptive and appropriate univariate tests, as well as multivariate stepwise logistic regression to determine predictors of survival. RESULTS: From 1991 to 1997, 9899 consecutive cardiac arrest cases with the following characteristics: male (67.2%), bystander-witnessed (44.7%), bystander CPR (14.2%), call response interval (CRI)

Developmental changes in the modulation of synaptic glycine receptors by ethanol.

During postnatal motoneuron development, the glycine receptor (GlyR) alpha subunit changes from alpha2 (fetal) to alpha1 (adult). To study the effect this change has on ethanol potentiation of GlyR currents in hypoglossal motoneurons (HMs), we placed neurons into two groups: neonate [postnatal day 1 to 3 (P1-3)], primarily expressing alpha2, and juvenile (P9-13), primarily expressing alpha1. We found that glycinergic spontaneous miniature inhibitory postsynaptic currents (mIPSCs) in neonate HMs are less sensitive to ethanol than in juveniles. Thirty millimolar ethanol increased the amplitude of juvenile mIPSCs but did not significantly change neonatal mIPSCs. However, 100 mM ethanol increased the amplitudes of both neonate and juvenile mIPSCs. There was a significant difference between age groups in the average ethanol-induced increase in mIPSC amplitude for 10, 30, 50, and 100 mM ethanol. In both age groups ethanol increased the frequency of glycinergic mIPSCs, but there was no difference in the amount of frequency increase between age groups. Ethanol (100 mM) also potentiated evoked IPSCs (eIPSCs) in both neonate and juvenile HMs. As we observed for mIPSCs, 30 mM ethanol increased the amplitude of juvenile eIPSCs, but had no significant effect on eIPSCs in neonate HMs. Ethanol also potentiated currents induced by exogenously applied glycine in both neonate and juvenile HMs. These results suggest that ethanol directly modulates the GlyR. To investigate possible mechanisms for this, we analyzed the time course of mIPSCs and single-channel conductance of the GlyR in the presence and absence of ethanol. We found that ethanol did not significantly change the time course of mIPSCs. We also determined that ethanol did not significantly change the single-channel conductance of synaptic GlyRs, as estimated by nonstationary noise analysis of mIPSCs. We conclude that the adult form of the native GlyR is more sensitive to ethanol than the fetal form. Further, enhancement of GlyR currents involves mechanisms other than an increase in the single-channel conductance or factors that alter the decay kinetics.

The circadian cycle of mPER clock gene products in the suprachiasmatic nucleus of the siberian hamster encodes both daily and seasonal time.

The circadian clock in the hypothalamic suprachiasmatic nuclei (SCN) regulates the pattern of melatonin secretion from the pineal gland such that the duration of release reflects the length of the night. This seasonally specific endocrine cue mediates annual timing in photoperiodic mammals. The aim of this study was to investigate how changes in photoperiod influence the cyclic expression of recently identified clock gene products (mPER and mTIM) in the SCN of a highly seasonal mammal, the Siberian hamster (Phodopus sungorus). Immunocytochemical studies indicate that the abundance of both mPER1 and mPER2 (but not mTIM) in the SCN exhibits very pronounced, synchronous daily cycles, peaking approximately 12 h after lights-on. These rhythms are circadian in nature as they continue approximately under free-running conditions. Their circadian waveform is modulated by photoperiod such that the phase of peak mPER expression is prolonged under long photoperiods. mPER1 protein is also expressed in the pars tuberalis of Siberian hamsters. In hamsters adapted to long days, the expression of mPER1 is elevated at the start of the light phase. In contrast, there is no clear elevation in mPER1 levels in the pars tuberalis of hamsters held on short photoperiods. These results indicate that core elements of the circadian clockwork are sensitive to seasonal time, and that encoding and decoding of seasonal information may be mediated by the actions of these transcriptional modulators.