Study of assessment of knowledge and understanding for coping with sick days among patients with diabetes in community pharmacy: a cluster randomized controlled trial (SAKURA trial).

BACKGROUND: Awareness regarding coping with sick days among patients with diabetes is limited. Thus, we evaluated the effectiveness of sick-day education by community pharmacists among patients with type 2 diabetes (T2D) using sick-day educational materials (sick-day cards). METHODS: A cluster randomized controlled trial was conducted. Pharmacists in the intervention group educated patients with T2D on coping with sick days (adjusting medication dosage and seeking medical advice) using sick-day cards compared with the usual counseling. Differences in questionnaire scores ("Anxiety", "Intention", "Attitude", and "Knowledge" about sick days) before and after the intervention were compared between the groups. RESULTS: Overall, 318 patients with T2D (intervention, 119; control, 199) participated in this study, and 270 (intervention, 92; control, 178) patients were examined. There were no significant differences in "Anxiety", "Intention", or "Attitude" scores between the two groups, but "Knowledge" scores improved in the intervention group. For all intervention groups (92/92), a physician reviewed and approved medication and adjustment doses for sick days on the cards. CONCLUSIONS: According to patients' responses, sick-day education using teaching materials improved patient knowledge. This may help patients and their caregivers cope with sick days appropriately through medication dose adjustment and fluid intake. Research registration number: UMIN000043161 (February 1, 2021), https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr.cgifunction=brows&action=brows&recptno=R000048124&type=summary&language=J.

Cystathionine ß-synthase inhibition is a potential therapeutic approach to treatment of ischemic injury.

Hydrogen sulfide (H2S) has been reported to exacerbate stroke outcome in experimental models. Cystathionine ß-synthase (CBS) has been implicated as the predominant H2S-producing enzyme in central nervous system. When SH-SY5Y cells were transfected to overexpress CBS, these cells were able to synthesize H2S when exposed to high levels of enzyme substrates but not substrate concentrations that may reflect normal physiological conditions. At the same time, these cells demonstrated exacerbated cell death when subjected to oxygen and glucose deprivation (OGD) together with high substrate concentrations, indicating that H2S production has a detrimental effect on cell survival. This effect could be abolished by CBS inhibition. The same effect was observed with primary astrocytes exposed to OGD and high substrates or sodium hydrosulfide. In addition, CBS was upregulated and activated by truncation in primary astrocytes subjected to OGD. When rats were subjected to permanent middle cerebral artery occlusion, CBS activation was also observed. These results imply that in acute ischemic conditions, CBS is upregulated and activated by truncation causing an increased production of H2S, which exacerbate the ischemic injuries. Therefore, CBS inhibition may be a viable approach to stroke treatment.

[Therapeutic effect of rebamipide for oral mucositis associated with FEC therapy for breast cancer].

No guidelines for supportive drug therapy have been established for oral mucositis occurring during cancer chemotherapy. We retrospectively examined the progression of oral mucositis in 91 patients with breast cancer who received the 5-fluorouracil, epirubicin, and cyclophosphamide (FEC)-100 regimen between September 2007 and August 2008. Daily rebamipide was administered to patients with oral mucositis as per hospital protocol to evaluate the hypothesized preventive and mucosal protective effects of rebamipide(Mucosta®). Oral mucositis was observed in 43 patients (47%)during 4 courses of FEC. The median age of the patients was 55 years(range, 32-76 years). Of the 91 patients, 49 patients who did not receive rebamipide during the 4 FEC courses were classified as group A, 14 patients who received rebamipide before the start of FEC were classified as group B, and 28 patients who received rebamipide after developing oral mucositis were classified as group C. The incidence of oral mucositis at the start of FEC with or without rebamipide administration was observed in 5 patients in group B (36%) and 38 patients in groups A and C (49%) (p=0.3472). The mucositis grade was G1 in 4 patients and G2 in 1 patient in group B, and G1 in 20 patients and G2 plus G3 in 18 patients in groups A and C (p=0.2467). In group C, the grade decreased in 25 patients (89%) and did not occur (G0) in 17 patients (61%) during the next course, and 15 patients (54%) continued to the final course without any occurrence of mucositis. These results suggest that rebamipide is effective for the treatment of oral mucositis. Although significant differences were not observed in the groups, rebamipide has the potential to prevent development of oral mucositis and alleviate its symptoms, and seems promising as a new supportive drug therapy. We hope to verify the preventive and protective effects of rebamipide by conducting a prospective, randomized trial while treating oral mucositis with basic oral care and appropriate interventions provided by a multidisciplinary team.

Organic nanoparticles with aggregation-induced emission for tracking bone marrow stromal cells in the rat ischemic stroke model.

Organic nanoparticles (NPs) with aggregation-induced emission (AIE) have been successfully used for tracking bone marrow stromal cells (BMSCs) in rats with ischemic stroke, highlighting the great potential of such fluorescent NPs in understanding the fate of transplanted stem cells for cell-based therapies.

Cytoplasmic translocation of the retinoblastoma protein disrupts sarcomeric organization.

Skeletal muscle degeneration is a complication arising from a variety of chronic diseases including advanced cancer. Pro-inflammatory cytokine TNF-α plays a pivotal role in mediating cancer-related skeletal muscle degeneration. Here, we show a novel function for retinoblastoma protein (Rb), where Rb causes sarcomeric disorganization. In human skeletal muscle myotubes (HSMMs), up-regulation of cyclin-dependent kinase 4 (CDK4) and concomitant phosphorylation of Rb was induced by TNF-α treatment, resulting in the translocation of phosphorylated Rb to the cytoplasm. Moreover, induced expression of the nuclear exporting signal (NES)-fused form of Rb caused disruption of sarcomeric organization. We identified mammalian diaphanous-related formin 1 (mDia1), a potent actin nucleation factor, as a binding partner of cytoplasmic Rb and found that mDia1 helps maintain the structural integrity of the sarcomere. These results reveal a novel non-nuclear function for Rb and suggest a potential mechanism of TNF-α-induced disruption of sarcomeric organization. DOI: http://dx.doi.org/10.7554/eLife.01228.001.

Charge-free reverse wormlike micelles in nonaqueous media.

We report a facile method for the formation of charge-free reverse wormlike micelles in a nonionic surfactant/oil system without addition of water under ambient conditions. This route involves the addition of sucrose dioleate (SDO) to semidilute solutions of sucrose trioleate (STO) in hexadecane. A reverse wormlike micelle was possible to achieve only with ionic surfactants in which water and/or salts are fundamentally required to induce micellar growth so far. In this contribution, we have shown that less lipophilic nonionic surfactant SDO promotes one-dimensional growth to STO reverse micelles and leads to the formation of transient networks of viscoelastic reverse wormlike micelles. The zero-shear viscosity increases by ∼4 orders of magnitude, and it is the mixing fraction of SDO to STO that determines the viscosity growth. The structure and dynamics of the reverse micelles are confirmed by small-angle X-ray scattering (SAXS) and rheometry measurements.

Transplanted olfactory mucosal cells restore paw reaching function without regeneration of severed corticospinal tract fibres across the lesion.

Previous studies from our laboratory reported that transplantation of a mixture of 50% p75+ olfactory ensheathing cells (OECs) and fibroblasts derived from the outer layers of the adult olfactory bulb into unilateral lesions of the rat corticospinal tract (CST) restore function in a directed fore-paw retrieval task and induce regeneration of severed CST axons across the lesion. For future clinical application it would be preferable to obtain reparative cells from an olfactory mucosal biopsy via intranasal endoscopy rather than requiring the more invasive intracranial approach to remove an olfactory bulb. With this purpose, we used our original CST lesion paradigm to examine whether mucosal OEC preparations can provide a similar repair to those from the bulb. We found that, as in the case of bulbar OEC preparations, the mucosal cells also restored directed fore-paw retrieval. Surprisingly, however, there was no evidence of any of the severed CST axons crossing the lesion site, suggesting that the recovery of function is due to some other reaction, such as sprouting of damaged or undamaged fibres. Compared with the previous findings with bulbar cells, the mucosal cell cultures contained only 5% of OECs and a conversely much larger proportion of fibroblasts. These cell preparations showed minimal migratory ability and failed to form complete bridges across the lesions.

Rheological properties of wormlike micellar solutions being available in wide temperature range in sucrose palmitate systems.

We investigated the melting point of the hydrated solid and rheological property of wormlike micellar solutions in the water/sucrose monopalmitate (C(16)SE)/tri (oxyethylene) dodecyl ether (C(12)EO(3)) system when a part of C(16)SE was substituted with the surfactants which have lower Krafft point than C(16)SE. The melting point of the hydrated solid of the water/C(16)SE/C(12)EO(3) system is around 34 degrees C. When C(16)SE is substituted with sodium dodecyl sulfate (SDS), the melting point of the hydrated solid decreases below 5 degrees C at alpha (weight fraction of SDS in C(16)SE+SDS mixture) being greater than 0.3 and the zero shear viscosity (eta(0)) increases from the original nonionic system. When C(16)SE is substituted with octa (oxyethylene) dodecyl ether (C(12)EO(8)), the melting point of the hydrated solid decreases down to 24 degrees C and the maximum zero shear viscosity (eta(0)(max)) decreases with the increase in alpha (weight fraction of C(12)EO(8) in C(16)SE+C(12)EO(8) mixture). eta(0)(max) is dramatically increased by the substitution of C(16)SE with SDS. With further increase of alpha, eta(0)(max) decreases gradually. The dynamic rheology data of highly viscous wormlike micellar solutions fit well to the Maxwell's mechanical model of viscoelastic material, indicating the formation of rigid network of entangled wormlike micelles. Shear (plateau) modulus G(0) is almost unchanged, whereas relaxation time tau(R) shows similar behavior to eta(0)(max). Hence, the behavior of eta(0)(max) can be explained from the behavior of tau(R) by considering the equation relating these quantities, eta(0)=G(0)tau(R). Since tau(R) is proportional to the length of wormlike micelles, the behavior of eta(0)(max) can be explained in terms of the change in the length of wormlike micelles caused by the addition of SDS.

An experimental model of ventral root repair showing the beneficial effect of transplanting olfactory ensheathing cells.

OBJECTIVE: A series of published cases show that repair of brachial plexus injuries by reimplantation of avulsed spinal roots can restore a degree of recovery, particularly to the more proximal shoulder and arm musculature in a proportion of patients. There remains, however, some disagreement regarding how far the benefits outweigh the risks of causing further spinal cord damage. Improving the number of motor fibers regenerating into the reimplanted ventral roots may enhance the muscular recovery, possibly extending it to the more useful distal musculature that would restore a degree of wrist and finger functions. METHODS: This study was based on our previous rat model showing regeneration of severed fibers and resumption of function after transplantation of cultured adult olfactory ensheathing cells into spinal cord injuries and reimplanted dorsal roots. RESULTS: We now report that olfactory ensheathing cells transplanted at the spinal cord interface of reimplanted S1 ventral roots survive and migrate selectively into the ventral root where they associate intimately with regenerating ventral root fibers. Whereas only approximately 20% of the normal complement of fibers enter roots reimplanted without olfactory ensheathing cells, this increases to 80% in the presence of olfactory ensheathing cell transplants. CONCLUSION: These observations suggest that transplants of olfactory ensheathing cells could improve the outcome of ventral root repair.