Supplementary Material for: Post Stroke Mirror Movements Preventing Performance of Bilateral Movements and Activities of Daily Living

Mirror movements (MMs) are involuntary synchronous movements of one limb during voluntary movements of the contralateral limb. Generally, MMs after stroke are observed in the unaffected hand during voluntary movements of the affected hand; MMs in the affected hand are comparatively rare. In previous studies, evaluation of MMs in the affected hand was performed using simple unilateral movement tasks, such as tapping or forceful repeated hand closure. However, the impact of MMs of the affected hand on functional tasks, such as activities of daily living (ADLs), has not been reported. We report the rare case of a patient with MMs of the affected hand due to atherothrombotic cerebral infarction of the right postcentral and precentral gyri. An 85-year-old Japanese man presented with left-sided hemiplegia and sensory impairment. MMs were observed in the left (affected) hand during many ADLs and could not be suppressed by the patient’s will even when the examiner verbally instructed the patient to move only the unaffected hand. The patient was aware that his hand moved on its own, but he could not control it. The patient was trained on various types of bilateral coordinated motor exercises for 114 days after the MMs were first identified. However, this did not affect MM occurrence, and the MMs remained at the time of discharge. Future research is necessary to plan long-term interventions for MMs of the affected hand

Supplementary Material for: Body Mass Index Change and Hospitalization Risk in Elderly Hemodialysis Patients: Results from Japanese Dialysis Outcomes and Practice Patterns Study

<b><i>Background:</i></b> Short-term weight gains and losses are associated with a lower and higher mortality risk, respectively, in patients undergoing hemodialysis (HD). However, little is known about their association with the risk of subsequent hospitalization. <b><i>Methods:</i></b> In a prospective cohort of 1,804 HD patients aged ≥65 years enrolled in the Japanese Dialysis Outcomes and Practice Patterns Study phases 3 (2005–2008) and 4 (2009–2011), we examined the associations between changes in body mass index (BMI) over a 4-month baseline period (<–3%, –3 to <–1%, –1 to <1% [reference], 1 to <3%, and ≥3%) and subsequent risk of all-cause, cardiovascular, and noncardiovascular hospitalization using Cox models with adjustment for potential confounders. <b><i>Results:</i></b> During a median follow-up of 1.2 years, we noted 1,028 incident hospitalizations for any cause, including 275 and 753 hospitalizations for cardiovascular and noncardiovascular causes, respectively. An L-shaped association was observed between BMI change and all-cause hospitalization. The multivariable-adjusted hazard ratios (HRs; 95% CI) of all-cause hospitalization associated with BMI changes of <–3%, –3 to <–1%, 1 to <3%, and ≥3% (vs. –1 to <1%) were 1.29 (1.01–1.65), 1.22 (0.98–1.51), 1.04 (0.83–1.29), and 1.10 (0.83–1.45), respectively. Qualitatively similar associations were present for cardiovascular-related hospitalization (corresponding HRs [95% CI]: 1.58 [1.06–2.37], 1.09 [0.75–1.58], 0.99 [0.72–1.36], and 0.91 [0.51–1.64], respectively) but not for noncardiovascular-related hospitalization (corresponding HRs [95% CI]: 1.19 [0.90–1.57], 1.26 [0.99–1.59], 1.06 [0.84–1.35], and 1.18 [0.86–1.63], respectively). <b><i>Conclusions:</i></b> Decreases in BMI over a relatively short-term period were independently associated with higher risk of subsequent hospitalization, particularly cardiovascular-related hospitalization, among elderly HD patients

Supplementary Material for: Use of Sotrovimab for COVID-19 in a patient with IGCCC Poor Prognosis testicular germ cell tumor

A 35-year-old man was diagnosed with stage IIIC non-seminoma with paralysis of the lower half of his body by 8th thoracic spine metastasis. The patient received bleomycin, etoposide, and cisplatin (BEP) therapy. On day 4 of the second course of BEP, the patient developed a fever and was diagnosed with coronavirus disease (COVID-19). COVID-19 was suspected to worsen because of cancer and chemotherapy-induced immunosuppression. However, the benefits of continuing BEP therapy outweighed these risks. After obtaining fully informed consent, BEP therapy was continued from day 5, while sotrovimab (anti-COVID-19 drug) was administered. The second course of BEP was completed without worsening severe COVID-19 or bleomycin-induced lung injury. The patient completed four courses of BEP, with normalization of tumor markers, partial response on imaging, and improvement in lower body paralysis. In this case, we successfully treated a patient with testicular germ cell tumor with chemotherapy while COVID-19 without treatment delay. During the COVID-19 pandemic, concomitant chemotherapy and COVID-19 treatment is warranted because delaying treatment will decrease the efficacy of highly curative diseases such as germ cell tumors

PowerPoint Slides for: Hypoxia-Inducible Factor-1α Activates the Transforming Growth Factor-β/SMAD3 Pathway in Kidney Tubular Epithelial Cells

<strong><em>Background:</em></strong> Kidney injury, including chronic kidney disease and acute kidney injury, is a worldwide health problem. Hypoxia and transforming growth factor-β (TGF-β) are well-known factors that promote kidney injury. Hypoxia-inducible factor (HIF) and SMAD3 are their main downstream transcriptional factors. Hypoxia-HIF pathway and TGF-β/SMAD3 pathway play a crucial role in the progression of kidney injury. However, reports on their interactions are limited, and the global transcriptional regulation under their control is almost unknown. <b><i>Methods:</i></b> Kidney tubular epithelial cells were cultured and stimulated by hypoxia and TGF-β. We detected global binding sites of HIF-1α and SMAD3 in cells using chromatin immunoprecipitation-sequencing (ChIP-Seq), and measured the gene expression using RNA-sequencing (RNA-Seq). ChIP-quantitative PCR (qPCR) was used to quantitatively evaluate bindings of SMAD3. <b><i>Results:</i></b> ChIP-Seq revealed that 2,065 and 5,003 sites were bound by HIF-1α and SMAD3, respectively, with 614 sites co-occupied by both factors. RNA-Seq showed that hypoxia and TGF-β stimulation causes synergistic upregulation of 249 genes, including collagen type I alpha 1 (COL1A1) and serpin peptidase inhibitor, clade E, member 1, which are well-known to be involved in fibrosis. Ontology of the 249 genes implied that the interaction of HIF-1α and SMAD3 is related to biological processes such as fibrosis. ChIP-qPCR of SMAD3 at HIF-1α binding sites near COL1A1 and SERPINE1 indicated that HIF-1α promotes the bindings of SMAD3, which is induced by TGF-β. <b><i>Conclusions:</i></b> These findings suggest that HIF-1α induced by hypoxia activates the TGF-β/SMAD3 pathway. This mechanism may promote kidney injury, especially by upregulating genes related to fibrosis

Supplementary Material for: Hypoxia-Inducible Factor-1α Activates the Transforming Growth Factor-β/SMAD3 Pathway in Kidney Tubular Epithelial Cells

<i>Background:</i> Kidney injury, including chronic kidney disease and acute kidney injury, is a worldwide health problem. Hypoxia and transforming growth factor-β (TGF-β) are well-known factors that promote kidney injury. Hypoxia-inducible factor (HIF) and SMAD3 are their main downstream transcriptional factors. Hypoxia-HIF pathway and TGF-β/SMAD3 pathway play a crucial role in the progression of kidney injury. However, reports on their interactions are limited, and the global transcriptional regulation under their control is almost unknown. <i>Methods:</i> Kidney tubular epithelial cells were cultured and stimulated by hypoxia and TGF-β. We detected global binding sites of HIF-1α and SMAD3 in cells using chromatin immunoprecipitation-sequencing (ChIP-Seq), and measured the gene expression using RNA-sequencing (RNA-Seq). ChIP-quantitative PCR (qPCR) was used to quantitatively evaluate bindings of SMAD3.<i>Results:</i> ChIP-Seq revealed that 2,065 and 5,003 sites were bound by HIF-1α and SMAD3, respectively, with 614 sites co-occupied by both factors. RNA-Seq showed that hypoxia and TGF-β stimulation causes synergistic upregulation of 249 genes, including collagen type I alpha 1 (COL1A1) and serpin peptidase inhibitor, clade E, member 1, which are well-known to be involved in fibrosis. Ontology of the 249 genes implied that the interaction of HIF-1α and SMAD3 is related to biological processes such as fibrosis. ChIP-qPCR of SMAD3 at HIF-1α binding sites near COL1A1 and SERPINE1 indicated that HIF-1α promotes the bindings of SMAD3, which is induced by TGF-β. <i>Conclusions:</i> These findings suggest that HIF-1α induced by hypoxia activates the TGF-β/SMAD3 pathway. This mechanism may promote kidney injury, especially by upregulating genes related to fibrosis