Case report: Rehabilitation course in thrombocytopenia, anasarca, fever, reticulin fibrosis/renal failure, and organomegaly syndrome complicated by cerebral infarction in the left parabolic coronary region.

Although thrombocytopenia, anasarca, fever, reticulin fibrosis/renal failure, and organomegaly (TAFRO) syndrome was first reported in 2010, its pathogenesis and prognosis are still unknown. Moreover, reports on rehabilitation in patients with TAFRO are limited. In severe cases, dyspnea and muscle weakness could impede improvements in activities of daily living (ADL). However, reports on exercise intensity showed no worsening of TAFRO within the load of 11-13 on the Borg scale. Herein, we describe the rehabilitation and progress in a 61-year-old woman with TAFRO syndrome complicated by cerebral infarction from early onset to discharge. After cerebral infarction onset in the perforating artery, she was admitted to the intensive care unit due to decreased blood pressure and underwent continuous hemodiafiltration. Two weeks following transfer to a general ward, the patient started gait training using a brace due to low blood pressure, respiration, and tachycardia. After initiating gait training, increasing the amount of training was difficult due to a high Borg scale of 15-19, elevated respiratory rate, and worsening tachycardia. Furthermore, there was little improvement in muscle strength on the healthy side after continuous training, owing to long-term steroid administration. On day 100 after transfer, the patient was discharged home with a T-cane gait at a monitored level. The patient had severe hemiplegia due to complications with severe TAFRO syndrome delaying early bed release and gait training; tachycardia; and respiratory distress. Additionally, delayed recovery from muscle weakness on the non-paralyzed side made it difficult for the patient to walk and perform ADLs. Despite these issues, low-frequency rehabilitation was useful. However, low-frequency rehabilitation with gait training, using a Borg scale 15-19 orthosis, did not adversely affect the course of TAFRO syndrome.

Voluntary running-induced activation of ventral hippocampal GABAergic interneurons contributes to exercise-induced hypoalgesia in neuropathic pain model mice.

The exact mechanism of exercise-induced hypoalgesia (EIH) in exercise therapy to improve chronic pain has not been fully clarified. Recent studies have suggested the importance of the ventral hippocampus (vHPC) in inducing chronic pain. We investigated the effects of voluntary running (VR) on FosB+ cells and GABAergic interneurons (parvalbumin-positive [PV+] and somatostatin-positive [SOM+]) in the vHPC-CA1 in neuropathic pain (NPP) model mice. VR significantly improved thermal hyperalgesia in the NPP model. The number of the FosB+ cells was significantly higher in partial sciatic nerve ligation-sedentary mice than in Sham and Naive mice, whereas VR significantly suppressed the FosB+ cells in the vHPC-CA1. Furthermore, VR significantly increased the proportion of activated PV+ and SOM+ interneurons in the vHPC-CA1, and tracer experiments indicated that approximately 24% of neurons projecting from the vHPC-CA1 to the basolateral nucleus of amygdala were activated in NPP mice. These results indicate that feedforward suppression of the activated neurons via VR-induced activation of GABAergic interneurons in the vHPC-CA1 may be a mechanism to produce EIH effects, and suggested that disappearance of negative emotions such as fear and anxiety by VR may play a critical role in improving chronic pain.

Exercise-induced increase in M2 macrophages accelerates wound healing in young mice.

Moderate-intensity exercise performed during wound healing has been reported to decrease inflammatory cytokines and chemokines and accelerate wound healing. However, its effect on macrophage phenotype and the mechanism by which exercise accelerates wound healing remain unclear. The purpose of this study was to investigate the effect of exercise on macrophage phenotype during wound healing and to clarify the relationship between angiogenesis and wound healing. 12-week-old male C57BL/6J mice were divided into sedentary (n = 6) and exercise groups (n = 6). The exercise group performed moderate-intensity treadmill running exercise (9.0 m/min, 60 min) for 10 days. Double immunofluorescence analysis was performed using F4/80+ inducible nitric oxide synthase (iNOS)+ for M1 macrophages, F4/80+ transforming growth factor-beta (TGF-ß)1+ for M2 macrophages, and CD31+ alpha smooth muscle actin (α-SMA)+ for angiogenesis. The exercise group showed significantly accelerated wound healing compared with the sedentary group. From early wound healing onward, exercise significantly inhibited M1 macrophage infiltration and increased M2 macrophage count. Exercise also significantly increased angiogenesis. Furthermore, the M2 macrophage phenotype was significantly correlated with angiogenesis in the exercise group, indicating that M2 macrophages and angiogenesis are related to accelerated wound healing. These findings suggest that moderate-intensity exercise increases TGF-ß1 derived from M2 macrophages, which may be associated with enhanced angiogenesis and wound healing in young mice.

Characteristics of falls occurring during rehabilitation in an acute care hospital in older and non-older patients: A retrospective cohort study.

Introduction: Although falls are often reported in hospitals and are common in older individuals, no reports on falls during rehabilitation exist. This study evaluated patients with falls occurring during rehabilitation and identified the characteristics of older and non-older patients. Materials and methods: Our study retrospectively analyzed reports of falls occurring during rehabilitation at a university hospital from April 1, 2020 to March 31, 2022. The survey items included the number of falls in the hospital as a whole and during rehabilitation, age, gender, modified Rankin Scale (mRS) before admission and at the time of fall, functional independence measure (FIM) at admission, patient communication status at the time of fall, and whether a therapist was near the patient. Patients aged ≥ 65 were considered older; aged ≤ 64, non-older; and those with the same age, gender, and clinical department, randomly selected as non-falling patients. Results: Thirty-five falls occurred during rehabilitation (14 in the non-older and 21 in the older patients), significantly lower than the 945 for the entire hospital, without any significant difference between non-older and older patients. No significant differences in mRS before admission and FIM at admission were noted for both groups in comparison with the non-falling patient group. Furthermore, gender, mRS, FIM, good communication status, and presence of therapist near the patient were similar between non-older and older patients (non-older 71.4%, older 52.4%). Most falls were minor adverse events that did not require additional treatment. Conclusion: The rate of falls during rehabilitation was much lower than that during hospitalization, and many falls had minimal impact on the patient. It was also difficult to predict falls in daily life and communication situations, and there was no difference in characteristics between the older and non-older groups. Since more than half of the falls occurred during training with the therapist, it is necessary to reconsider the training content.

Effect of coronary artery bypass grafting on blood pressure response to head-up tilting.

Blood pressure response to head-up tilt (HUT) in 7 healthy subjects and 9 patients before and after coronary artery bypass grafting (CABG) was measured during supine and 15-min 60° HUT. Stroke volume (SV) and ejection fraction (EF) were assessed by echocardiography. Baseline mean arterial pressure (MAP) and heart rate (HR) in patients before CABG were similar to healthy subjects. MAP in patients decreased by 6 (4-9) mmHg [median (1st-3rd quartiles)] during 7-12 mmHg of HUT with decreased cardiac output (CO = SV × HR) while HR remained unchanged. MAP in healthy subjects remained unchanged during HUT with increased HR. Body weight decreased by 3.5 (2.5-3.7) kg and MAP decreased by 6 (2-13) mmHg during the last 3-min HUT while HR increased after CABG. Decreases in SV and CO during HUT disappeared after CABG. Blood pressure decreased during HUT in patients before and after CABG regardless of HR response.

Phosphorylation states change Otx2 activity for cell proliferation and patterning in the Xenopus embryo.

The homeodomain transcription factor Otx2 has essential roles in head and eye formation via the negative and positive regulation of its target genes, but it remains elusive how this dual activity of Otx2 affects cellular functions. In the current study, we first demonstrated that both exogenous and endogenous Otx2 are phosphorylated at multiple sites. Using Xenopus embryos, we identified three possible cyclin-dependent kinase (Cdk) sites and one Akt site, and analyzed the biological activities of phosphomimetic (4E) and nonphosphorylatable (4A) mutants for those sites. In the neuroectoderm, the 4E but not the 4A mutant downregulated the Cdk inhibitor gene p27xic1 (cdknx) and posterior genes, and promoted cell proliferation, possibly forming a positive-feedback loop consisting of Cdk, Otx2 and p27xic1 for cell proliferation, together with anteriorization. Conversely, the 4A mutant functioned as an activator on its own and upregulated the expression of eye marker genes, resulting in enlarged eyes. Consistent with these results, the interaction of Otx2 with the corepressor Tle1 is suggested to be phosphorylation dependent. These data suggest that Otx2 orchestrates cell proliferation, anteroposterior patterning and eye formation via its phosphorylation state.