BCKDK, A Novel Hypoxia-Responsive Kinase That Exacerbates Cerebral Ischemia Injury

 How long before your incompetent? doctor and hospital even know about this? I'm guessing never based on past behaviour!

Exacerbate is a verb that means to make a bad situation, problem, pain, or illness worse

BCKDK, A Novel Hypoxia-Responsive Kinase That Exacerbates Cerebral Ischemia Injury

Boya Liao, PhD, MSocSc(Psy) https://orcid.org/0000-0001-7659-8406, Fang Zhang, MD https://orcid.org/0000-0002-4634-2749, 

Chang Han, MPhil https://orcid.org/0000-0002-6282-1256, Xinyao Yi, MSc, 

Ziyi Zhang, MPhil, Leigang Jin, PhD https://orcid.org/0000-0002-6916-4009,

Fei Meng, MSc https://orcid.org/0000-0002-8750-7896, Stanley Sau-Ching Wong, MD https://orcid.org/0000-0002-8763-5687, 

Ruby L.C. Hoo, PhD https://orcid.org/0000-0001-9633-7078 rubyhoo@hku.hk, Leiluo Geng, PhD https://orcid.org/0000-0003-2886-3476 llgeng@hku.hk, and Wei Jia, PhD https://orcid.org/0000-0002-3739-8994 weijia2@hku.hkAuthor Info & Affiliations

Stroke

New online

https://doi.org/10.1161/STROKEAHA.125.053856

Abstract

BACKGROUND:

Alterations in circulating amino acid profiles have been observed in ischemic stroke patients; however, whether cerebral ischemia disrupts amino acid metabolism within brain tissue and whether this disruption contributes to cellular stress and cerebral injury remain unknown. This hypothesis-testing study investigates disrupted BCAA (branched-chain amino acid) catabolism as a key mechanism of ischemic brain damage and evaluates BCKDK (branched-chain α-keto acid dehydrogenase kinase) as a novel therapeutic target.

METHODS:

Mouse primary cortical neurons subjected to oxygen-glucose deprivation and brain tissue from a mouse acute ischemic stroke model were used as experimental systems. Untargeted metabolomics and metabolic flux analysis were used to characterize BCAA metabolism in both models. In vivo pharmacological inhibition or in vitro knockdown of BCKDK was performed using BT2 treatment or RNA interference. Primary outcome variables included infarct volume, BCKDH (branched-chain α-keto acid dehydrogenase) enzyme activity, neuronal viability, and markers of energy metabolism and glutamate excitotoxicity. Between-group differences were evaluated using 1-way ANOVA; data are presented as mean ± SD with 95% CIs and corresponding P values.

RESULTS:

Metabolomics analysis of oxygen-glucose deprivation-exposed primary neurons revealed impaired BCAA catabolism and significant BCAA accumulation compared with normoxic controls. In ischemic mouse brain tissue, BCKDH activity was significantly suppressed, and BCKDK expression was markedly upregulated relative to sham-operated animals. Both pharmacological and genetic suppression of BCKDK substantially reduced cerebral ischemic injury, as evidenced by decreased infarct volume and improved neuronal survival (95% CI and P values per comparison). Mechanistically, ischemia-induced BCKDK expression via HIF-1α (hypoxia-inducible factor 1α)-mediated transcriptional activation, which inhibited BCAA conversion to tricarboxylic acid cycle substrates, thereby potentiating energy deficiency and glutamate excitotoxicity.

CONCLUSIONS:

These data identify BCKDK as a novel hypoxia-responsive factor whose upregulation drives disrupted BCAA catabolism as a key mechanism of ischemic neuronal injury. BCKDK represents a promising therapeutic target for cerebral ischemia, directly supported by both in vitro and in vivo experimental evidence presented here.(Which doesn't correspond to exacerbates in the title! So which is it? Your mentors and senior researchers are so incompetent they didn't catch that?)

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Correlations of systemic immune-inflammation index and systemic inflammation response index with the risk for early-onset post-stroke depression in patients with minor stroke: a prospective observational study

 Why work on this rather than PREVENTING DEPRESSION WITH EXACT 100% RECOVERY PROTOCOLS?

Don't your mentors and senior researchers know the correct way to deal with problems? Prevent them!

Correlations of systemic immune-inflammation index and systemic inflammation response index with the risk for early-onset post-stroke depression in patients with minor stroke: a prospective observational study

• W

  Wei Zhao 1†

• 

  Mingzhu Deng 2†

• 

  Zhen Wang 1

• 

  Guohua He 1

• 

  Wei Xu 1

• T

  Tieqiao Feng 1

• J

  Jian Peng 1

• 

  Kangping Song 1

• L

  Ling Xiao 1*

• 

  Fangyi Li 1*

• 1. Department of Neurology, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha, Hunan, China

• 2. Department of Neurology, The Second People’s Hospital of Hunan Province (Brain Hospital of Hunan Province), Changsha, Hunan, China

Abstract

Background: 

Inflammation plays a pivotal role in the pathophysiology of post-stroke depression (PSD). However, the relationship between novel systemic inflammatory indices-the systemic immune-inflammation index (SII) and systemic inflammation response index (SIRI)-and early-onset PSD remains inadequately explored.

Methods: 

Early-onset PSD was diagnosed 2 weeks after acute ischemic stroke (AIS). Depression severity was assessed using the 17-item Hamilton Depression Rating Scale (HAMD-17); patients with scores ≥7 were classified into the early-onset PSD group. Spearman rank correlation analysis was performed to evaluate associations of SII and SIRI with HAMD-17 scores across all participants. Binary logistic regression was used to examine the independent associations of SII and SIRI with early-onset PSD. Receiver operating characteristic (ROC) analysis was employed to assess the SII and SIRI capacity to differentiate early-onset PSD.

Results: 

Of the 1,113 prospectively enrolled patients, 372 (33.42%) were diagnosed with early-onset PSD. HAMD-17 scores showed significant positive correlations with SII (r = 0.440, p < 0.001) and SIRI (r = 0.418, p < 0.001). Both SII (OR = 1.762, 95% CI: 1.261–1.946, p < 0.001) and SIRI (OR = 1.672, 95% CI: 1.348–1.932, p = 0.004) emerged as independent predictors of early-onset PSD. The areas under the curve (AUC) for SII, SIRI, and their combination were 0.767, 0.718, and 0.807, respectively.

Conclusion: 

SII and SIRI may serve as independent risk factors for early-onset PSD. These indices offer potential utility for risk stratification and could inform prevention strategies and prognosis management in this patient population.

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Towards routine biomechanical data collection in stroke rehabilitation: a usability comparison of IMU and markerless motion capture systems for functional upper-limb assessments

  'Assessments' DO NOTHING FOR RECOVERY! With no protocols based on the assessment; THIS WAS COMPLETELY FUCKING USELEESS! You're all fired! You, your mentors and senior researchers are obviously clueless on how to get survivors recovered! I'd suggest basket weaving for your mental capacity.

Towards routine biomechanical data collection in stroke rehabilitation: a usability comparison of IMU and markerless motion capture systems for functional upper-limb assessments

• Tim Unger,
• Xin Yao,
• Anna Schmitt,
• Lea Cebulla &
• Chris Easthope Awai 

We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply.

Abstract

Objective measurement of upper-limb movement quality based on biomechanical data collected in clinical routine has the potential to enable precision neurorehabilitation at scale. However, integrating biomechanical data collection into daily clinical workflows remains challenging. In this exploratory study, we evaluated the usability of two technologies for routine kinematic data collection: an IMU-based version of the instrumented Action Research Arm Test (iARAT-IMU) and a MMC markerless motion capture (MMC) system. First, five physiotherapists independently operated the iARAT-IMU across seven clinical routine assessment sessions at a rehabilitation clinic in Switzerland to quantify learning curves, setup times, and usability. Second, we conducted a preference study in which the same therapists used both, the IMU- and MMC-system, during a standardized drinking task and completed quantitative and qualitative usability assessments focusing on system preference and underlying reasons. Results show that therapists rapidly learned to operate the tablet application for scoring the iARAT; however, the IMU system added approximately 11 min of setup time and sometimes required assistance. In contrast, the MMC workflow required approximately 2 min of additional time - well within the 5-minute maximum indicated a priori by therapists as acceptable for clinical routine and received consistently higher usability ratings. Most therapists preferred this approach due to greater efficiency and reduced patient burden. These findings highlight important design considerations for future digital assessment tools and indicate that MMC systems may offer a more feasible pathway toward routine biomechanical data collection for upper-limb assessments in clinical neurorehabilitation.

Towards routine biomechanical data collection in stroke rehabilitation: a usability comparison of IMU and markerless motion capture systems for functional upper-limb assessments

 'Assessments' DO NOTHING FOR RECOVERY! With no protocols based on the assessment; THIS WAS COMPLETELY FUCKING USELEESS! You're all fired! You, your mentors and senior researchers are obviously clueless on how to get survivors recovered! I'd suggest basket weaving for your mental capacity.

Towards routine biomechanical data collection in stroke rehabilitation: a usability comparison of IMU and markerless motion capture systems for functional upper-limb assessments

• Tim Unger,
• Xin Yao,
• Anna Schmitt,
• Lea Cebulla &
• Chris Easthope Awai 

We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply.

Abstract

Objective measurement of upper-limb movement quality based on biomechanical data collected in clinical routine has the potential to enable precision neurorehabilitation at scale. However, integrating biomechanical data collection into daily clinical workflows remains challenging. In this exploratory study, we evaluated the usability of two technologies for routine kinematic data collection: an IMU-based version of the instrumented Action Research Arm Test (iARAT-IMU) and a MMC markerless motion capture (MMC) system. First, five physiotherapists independently operated the iARAT-IMU across seven clinical routine assessment sessions at a rehabilitation clinic in Switzerland to quantify learning curves, setup times, and usability. Second, we conducted a preference study in which the same therapists used both, the IMU- and MMC-system, during a standardized drinking task and completed quantitative and qualitative usability assessments focusing on system preference and underlying reasons. Results show that therapists rapidly learned to operate the tablet application for scoring the iARAT; however, the IMU system added approximately 11 min of setup time and sometimes required assistance. In contrast, the MMC workflow required approximately 2 min of additional time - well within the 5-minute maximum indicated a priori by therapists as acceptable for clinical routine and received consistently higher usability ratings. Most therapists preferred this approach due to greater efficiency and reduced patient burden. These findings highlight important design considerations for future digital assessment tools and indicate that MMC systems may offer a more feasible pathway toward routine biomechanical data collection for upper-limb assessments in clinical neurorehabilitation.

A Compact Wearable sEMG–FES System for Bilateral Post-Stroke Rehabilitation

 No clue what this can do to get survivors recovered. A complete failure of the mentors and senior researchers to state EXACTLY what stroke research is for; TO GET SURVIVORS RECOVERED!

No protocols delivered or results discussed; so useless!

A Compact Wearable sEMG–FES System for Bilateral Post-Stroke Rehabilitation

Martina Vita; Giuseppe Coviello; Maurizio Pellegrini; Giuseppe Brunetti; Caterina Ciminelli

All Authors

 

Abstract:

 Stroke-related upper limb motor impairment frequently leads to chronic muscle weakness and reduced functional mobility, significantly affecting patients’ independence and quality of life. Functional Electrical Stimulation (FES) combined with surface electromyography (sEMG) feedback has shown significant potential in promoting neuroplasticity and supporting motor recovery by reinforcing the association between voluntary intention and muscle activation. However, existing systems typically rely on multiple independent devices for signal acquisition, processing and stimulation. This fragmented architecture increases cost, size, latency and integration complexity. This work presents a new wearable hardware platform that integrates sEMG acquisition and FES delivery within a single compact module. The proposed solution embeds an ADS1299- based front-end for low-noise sEMG recording and a digitally controlled high-voltage stimulator, enabling simultaneous acquisition and stimulation in two muscle groups. The platform supports a bilateral closed-loop rehabilitation paradigm in which voluntary sEMG activity recorded from the dominant arm is used to drive FES delivered to the contralateral limb. In this study, a trigger-based control strategy is adopted, whereby stimulation is activated when the root mean square (RMS) of the processed sEMG signal exceeds an adaptive threshold, and preliminary experimental results demonstrate the feasibility of the proposed system for bilateral sEMG-driven FES applications in post-stroke rehabilitation.

Endovascular Therapy for Medium-Vessel Occlusion Stroke — Narrowing the Target Population

 Don't you know the goal is to leave no survivor behind AND provide EXACT 100% recovery protocols? Or did your mentors and senior researchers incompetently fail to tell you about survivor goals? NOT YOUR DOCTOR OR THERAPISTS GOALS!

Endovascular Therapy for Medium-Vessel Occlusion Stroke — Narrowing the Target Population

Authors: Johanna M. Ospel, M.D., Ph.D., and Michael D. Hill, M.D. https://orcid.org/0000-0002-6269-1543Author Info & Affiliations

Published May 13, 2026

N Engl J Med 2026;394:1955-1957

DOI: 10.1056/NEJMe2601852

VOL. 394 NO. 19

Copyright © 2026

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Abstract

One way to classify acute ischemic stroke is by the anatomy of vessel occlusion. Initial randomized trials of endovascular thrombectomy focused on large-vessel occlusions.^1-5 These proximal occlusions of the intracranial carotid artery or the stem of the middle cerebral artery (MCA) represent the most severe form of anterior circulation ischemic stroke. The large clinical benefit from endovascular thrombectomy is consistent with the patent artery hypothesis and reperfusion associated with intravenous thrombolysis. Reperfusion success after endovascular thrombectomy is now routinely achieved in 90% of patients, but early reperfusion, as measured with computed tomographic (CT) angiography at approximately 2 to 4 hours . . .

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Association between intracranial arterial stenosis severity and recurrent stroke risk in elderly ischemic stroke patients

 Why do 'association' research instead of EXACTLY PREVENTING this problem from occurring?  Your mentors and senior researchers incompetently didn't tell you that stroke research is supposed to solve survivors problems?

Association between intracranial arterial stenosis severity and recurrent stroke risk in elderly ischemic stroke patients

• Z

  Zhen Tao 1

• 

  Hongwei Guo 2*

• Y

  Yingying Liu 2

• 

  Jun-Bin Yin 2

• 

  Hu Huai Qiang 2

• H

  Haowen Lu 2

• 1. No. 971 Hospital of the People's Liberation Army Navy, Qingdao, China

• 2. Department of Neurology, The 960(th) Hospital of Joint Logistics Support, PLA, Jinan, China

Abstract

Background and aim: 

Intracranial arterial stenosis (ICAS) is a major cause of ischemic stroke in older adults and is associated with substantial risk of recurrent cerebrovascular events. Whether increasing ICAS severity confers incremental recurrence risk in medically treated elderly patients in routine clinical practice remains incompletely characterized. This study aimed to investigate the association between intracranial arterial stenosis severity and 12-month recurrent stroke risk in elderly patients with ischemic stroke.

Methods: 

This single-center retrospective cohort study screened 614 consecutive patients aged 65 years or older who were admitted with acute ischemic stroke between January 2022 and December 2023. After predefined exclusions, 527 patients were included in the final analysis. Intracranial arterial stenosis was assessed using computed tomography angiography or magnetic resonance angiography and categorized as none-to-mild (<50%; including no stenosis), moderate (50–69%), or severe (≥70%) according to the highest-grade lesion. The primary outcome was recurrent ischemic stroke within 12 months. Univariable and multivariable logistic regression models were used to evaluate independent predictors of recurrence.

Results: 

Among the 527 included patients, recurrent ischemic stroke occurred in 86 (16.3%) during 12-month follow-up. Recurrence rates increased stepwise across stenosis categories, occurring in 18/214 (8.4%) patients with none-to-mild stenosis, 29/173 (16.8%) with moderate stenosis, and 39/140 (27.9%) with severe stenosis (p < 0.001). After adjustment for age, sex, vascular risk factors, stroke subtype, baseline NIHSS score, and medication use, severe ICAS remained independently associated with recurrent stroke (adjusted OR 3.12, 95% CI 1.85–5.26, p < 0.001); moderate stenosis was also independently associated with recurrence (adjusted OR 1.96, 95% CI 1.04–3.69, p = 0.037).

Conclusion: 

In elderly patients with ischemic stroke, greater intracranial arterial stenosis severity is independently associated with higher 12-month recurrence risk despite contemporary medical management. These findings support early vascular imaging and risk stratification in elderly patients with ischemic stroke.