Stable kinetochore-microtubule attachments restrict MTOC position and spindle elongation in oocytes.

In mouse oocytes, acentriolar MTOCs functionally replace centrosomes and act as microtubule nucleation sites. Microtubules nucleated from MTOCs initially assemble into an unorganized ball-like structure, which then transforms into a bipolar spindle carrying MTOCs at its poles, a process called spindle bipolarization. In mouse oocytes, spindle bipolarization is promoted by kinetochores but the mechanism by which kinetochore-microtubule attachments contribute to spindle bipolarity remains unclear. This study demonstrates that the stability of kinetochore-microtubule attachment is essential for confining MTOC positions at the spindle poles and for limiting spindle elongation. MTOC sorting is gradual and continues even in the metaphase spindle. When stable kinetochore-microtubule attachments are disrupted, the spindle is unable to restrict MTOCs at its poles and fails to terminate its elongation. Stable kinetochore fibers are directly connected to MTOCs and to the spindle poles. These findings suggest a role for stable kinetochore-microtubule attachments in fine-tuning acentrosomal spindle bipolarity.

Medications and fall risk: a case-control study in nursing home residents in Japan.

AIM: Falls are a significant problem for older people, but are few studies of the risk of falling in residents of nursing homes in Japan. We aimed to investigate the risk factors for falls and the association of medication use and falls in nursing home residents in Japan. METHODS: This case-control study reviewed the records of residents of who were ≥ 65 years of age and had fallen in 2012 and an age-, sex-, and facility-matched control group selected from 58 nursing homes in Japan. The odds ratios of potential risk factors and current medications were determined by conditional logistic regression. RESULTS: A total of 1832 residents (916 cases and 916 controls) were included. Falls were significantly associated with an inability to walk without assistance or stand up without assistance, need for toileting assistance, visual impairment, insomnia, and dementia. Current prescription of antithrombotic, nonsteroidal anti-inflammatory, or antiparkinson drugs, muscle relaxants, antiepileptics, antipsychotics, antidepressants, opioids, selective serotonin reuptake inhibitors, and memantine was also associated with increased risk of falling. CONCLUSIONS: Many medications were associated with falls in nursing homes residents in Japan. To prevent these falls, caregivers should provide adequate care, and healthcare professionals should consider switching or dose reduction for these medications.

Up-regulation of pro-apoptotic protein Bim and down-regulation of anti-apoptotic protein Mcl-1 cooperatively mediate enhanced tumor cell death induced by the combination of ERK kinase (MEK) inhibitor and microtubule inhibitor.

Blockade of the ERK signaling pathway by ERK kinase (MEK) inhibitors selectively enhances the induction of apoptosis by microtubule inhibitors in tumor cells in which this pathway is constitutively activated. We examined the mechanism by which such drug combinations induce enhanced cell death by applying time-lapse microscopy to track the fate of individual cells. MEK inhibitors did not affect the first mitosis after drug exposure, but most cells remained arrested in interphase without entering a second mitosis. Low concentrations of microtubule inhibitors induced prolonged mitotic arrest followed by exit of cells from mitosis without division, with most cells remaining viable. However, the combination of a MEK inhibitor and a microtubule inhibitor induced massive cell death during prolonged mitosis. Impairment of spindle assembly checkpoint function by RNAi-mediated depletion of Mad2 or BubR1 markedly suppressed such prolonged mitotic arrest and cell death. The cell death was accompanied by up-regulation of the pro-apoptotic protein Bim (to which MEK inhibitors contributed) and by down-regulation of the anti-apoptotic protein Mcl-1 (to which microtubule and MEK inhibitors contributed synergistically). Whereas RNAi-mediated knockdown of Bim suppressed cell death, stabilization of Mcl-1 by RNAi-mediated depletion of Mule slowed its onset. Depletion of Mcl-1 sensitized tumor cells to MEK inhibitor-induced cell death, an effect that was antagonized by knockdown of Bim. The combination of MEK and microtubule inhibitors thus targets Bim and Mcl-1 in a cooperative manner to induce massive cell death in tumor cells with aberrant ERK pathway activation.

Preparation of tricationic tris(pyridylpalladium(II)) metallacyclophane as an anion receptor.

A tricationic tris(pyridylpalladium(II)) metallacyclophane was prepared from 3,5-dibromopyridine by a successive treatment with tetrakis(triphenylphosphine)palladium(0), diphosphine, and silver salt. Single-crystal X-ray diffraction analysis revealed that the metallacyclophane incorporated one of three counter anions into its hole-shaped cavity to form multidentate C-H⋯anion interactions. Solution-phase 1H NMR experiments in DMSO-d6 indicated that the metallacyclophane exhibited selective binding behavior toward nitrate, tetrafluoroborate, p-toluenesulfonate, perchlorate, and hydrogen sulfate ions, whereas the hexafluoroantimonate ion exhibited only weak interaction toward the metallacyclophane. This anion recognition behavior was further demonstrated by an extraction experiment of water-soluble sulfonate dyes.

What the Desirable Collaboration between Care Workers in Nursing Homes and Phamacists Should Be: An Approach for Security and Safe Medication for Residents in Nursing Homes.

In our previous research, there was no collaboration between care workers and pharmacists, for the most part. As a result, it was discovered that in some cases, problems concerning medication of nursing home residents had not been resolved. To solve this issue, we brought together care workers and pharmacists for a workshop we conducted. We assigned 12 care workers with at least two years of experience and 12 pharmacists to four mixed groups and guided them in the management of in-home long-term medical care and conducted small group discussions (SGD) using the KJ method. In the pre-survey before the workshop, all 12 care workers replied "yes" to having experienced "concerns over medication" and nine (75%) replied "no" to having experienced "discussions (consultations) with pharmacists regarding the medication of residents". As a result of the SGD, "information sharing among professionals" was revealed as a problem common to all groups. Furthermore, common countermeasures for this issue included communication notes and holding collaborative meetings. In the post-survey after the workshop, 67% of the participants replied that their thoughts concerning countermeasures were "coherent", and everyone replied that their "awareness was increased". In a follow-up survey after the workshop, 82% of the participants replied that they were using some form of what they had learned and discovered in the workshop in their actual work.

An Approach for Safe Medication Assistance in Nursing Homes: A Workshop to Identify Problems of and Plan Measures for Care Workers.

We conducted a workshop that aimed to clarify problems with care workers supporting medication use in nursing homes, to propose measures for solving these problems, and to raise awareness of these problems among care workers. Eighteen care workers from different fee-based elderly nursing homes were enrolled in the workshop, and divided into four groups. The participants in these groups identified the issues based on their experiences regarding medication-related incidents, and discussed related problems and viable measures using the KJ method. The issues identified by each group were "dropping a medication", "wrong resident", "refusal to take medication", and "confusion". To resolve these problems, the participants recommended: "conducting study sessions or testing of manuals and medication knowledge", "strengthening monitoring systems", "enhancing information sharing", etc. The involvement of pharmacists was hardly mentioned, despite the workshop being designed for "medication assistance". A post-workshop questionnaire revealed that 88.9% of the participants acknowledged an increased awareness of safe assistance in the use of medication. A follow-up questionnaire, distributed approximately seven months after the workshop, revealed that 82.4% of participants applied the experience and knowledge they learned at the workshop to their work. The workshop seemed to raise awareness and lead to preventive measures for safe medication assistance. Communication between care workers and other health care professionals, such as pharmacists, is important to designing and implementing safe medical care in nursing homes.