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Joined March 2026
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1/ Today's 🧵is about "VT" versus "SVT with aberrancy".
The aim of this thread is to provide basic tips on how to apply some of the most used criteria that might be helpful in diagnosing VT. #CardioTwitter
Note that the following features are suggestive of VT, but their absence does not exclude VT.
@ekgdx
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7.5-8.5 hr time in bed is accurate.
6.5-7.5 hr of sleep is ideal which means 7.5-8.5 hr time in bed assuming 85-90% efficiency. The below graph is self reported from questionnaire. 7 hr in bed is too short.
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Video of myosin proteins "walking" along actin. Insane that we can image this!
It was made by Toshio Ando's group using atomic force microscopy. All of their papers are a goldmine; they've also recorded a Cas9 protein cutting DNA and ATP synthase spinning.
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This week in medicine
- Regeneron discover a new target for metabolic syndrome: FNIP1
- Takeda’s oveporexton becomes the first approved medicine that targets the underlying biological cause in narcolepsy
- Lilly expands the potential indications for their neuroscience GLP1/GIP agonist, brenipatide, with trials in IBS
- Revolution Medicines' RAS G12D inhibitor, zoldonrasib, achieves 82% ORR (alongside chemo-immunotherapy) in non-small-cell lung cancer
- Sanger and Broad institutes discover new cancer drug targets, using patient-derived organoids and 3D models
- Otsuka’s sibeprenlimab halts progression of IgA nephropathy for at least 2 years
- Genentech discover pyroptosis inhibitors (that could help treat sepsis)
- Psilocybin produces a huge antidepressant effect -- in a public healthcare system
- CG Oncology's oncolytic virus therapy enables surgery-sparing bladder cancer treatment
- Replimune’s oncolytic virus (finally) gets FDA approval
More here! breakingground.substack.com/…
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🧬 Mitochondrial RNA stability: a new metabolic vulnerability in colorectal cancer
Cancer metabolism is often framed through the Warburg effect — increased glycolysis despite oxygen availability. However, many solid tumors, particularly highly vascularized cancers such as colorectal cancer (CRC), maintain strong dependence on oxidative phosphorylation (OXPHOS).
A new study in British Journal of Cancer identifies SLIRP (SRA stem-loop interacting RNA-binding protein) as a critical mitochondrial regulator that allows CRC cells to sustain OXPHOS by stabilizing mitochondrial-encoded mRNAs.
🔹 The central discovery
SLIRP is a mitochondrial RNA-binding protein (Mito-RBP) that binds mitochondrial transcripts and protects them from degradation.
CRC tissues showed:
• Increased SLIRP expression compared with normal tissue
• Higher SLIRP levels associated with poorer patient survival
• Mitochondrial localization confirmed in CRC cells and patient samples
Mechanistically, SLIRP acts as a molecular “stabilizer” for the mitochondrial genome.
Mitochondrial DNA encodes 13 essential proteins forming respiratory chain complexes I, III, IV and V. SLIRP binds these mitochondrial mRNAs and maintains their stability, preserving respiratory chain assembly and ATP production.
🔹 What happens when SLIRP is removed?
Loss of SLIRP creates a mitochondrial energy crisis:
SLIRP knockdown →
↓ mitochondrial mRNA stability
↓ respiratory chain components
↓ oxygen consumption & OXPHOS
↓ ATP production
→ apoptosis and tumor growth suppression
In CRC models, SLIRP depletion reduced proliferation, inhibited colony formation, and suppressed xenograft tumor growth.
Interestingly, cancer cells initially attempted metabolic adaptation:
OXPHOS failure → temporary glycolytic activation → insufficient compensation → metabolic collapse.
This demonstrates that CRC cells possess metabolic plasticity, but SLIRP-dependent mitochondrial maintenance represents a critical dependency.
🔹 Therapeutic implications
Current OXPHOS inhibitors targeting mitochondrial complex I show anticancer activity but are limited by toxicity.
SLIRP represents a different strategy:
Instead of directly blocking respiration,
→ selectively disrupt the mitochondrial RNA maintenance system that tumors rely on.
The authors propose SLIRP as:
✅ a prognostic biomarker
✅ an OXPHOS-related therapeutic target
✅ a potential safer alternative for metabolic intervention in CRC
🔬 Broader significance
This study expands cancer metabolism beyond glycolysis versus respiration.
The future battlefield may be mitochondrial information control:
DNA → RNA stability → respiratory complex assembly → ATP production → tumor survival
Targeting mitochondrial RNA biology could become a new layer of precision metabolic therapy.
#CancerMetabolism #ColorectalCancer #Mitochondria #OXPHOS #RNAbiology #TumorMetabolism #PrecisionOncology
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Medio litro de agua media hora antes de comer y un 44% más de pérdida de peso en 12 semanas. Suena a chorrada de revista de sala de espera, pero el mecanismo es aburrido y real: distensión gástrica, señal de saciedad antes de que llegue la comida. Y encima sale gratis.
drinking 500ml of water 30 minutes before every meal to lose weight sounds like advice from a magazine in a dentist's office until you read the clinical trial showing it increased weight loss by 44% over 12 weeks with no other changes. then it sounds like the stupidest simple intervention that actually has peer reviewed data behind it
the mechanism is mechanical and hormonal. water physically stretches the stomach wall which activates stretch receptors that send fullness signals to the brain through the vagus nerve. you feel more full before the first bite. simultaneously, the water dilutes the concentration of ghrelin (hunger hormone) in the stomach, reducing the hunger signal's intensity. that's it. stretch plus dilution equals eating less without trying
- a study published in Obesity had participants drink 500ml of water 30 minutes before each meal. the water group lost 44% more weight than the control group over 12 weeks. no other dietary changes were made. the only variable was the water
- participants naturally consumed 75-90 fewer calories per meal after pre-loading with water. across 3 meals that's 225-270 fewer calories per day without any conscious restriction
- the pre-meal water also improved hydration status which increased resting metabolic rate by 24-30% for 60 minutes after drinking. cold water has a slightly higher thermic effect because the body expends energy warming it
- dehydration is often misinterpreted as hunger by the brain. the hypothalamic signaling for thirst and hunger overlap. many "hunger" signals between meals are actually dehydration. the water eliminates the false signal
- improved hydration supports kidney and liver function which are the primary organs of fat metabolism. a dehydrated liver metabolizes fat 20% slower than a hydrated one
- zero side effects. zero cost. zero willpower required. the most accessible weight loss intervention possible
the weight loss industry charges $200/month for meal delivery services designed to control portion size. a glass of water before the meal accomplishes the same portion control through your body's own satiety signaling for free. there's no subscription revenue in "drink water before eating" so you'll never see it in a sponsored post
500ml (roughly 16oz or 2 glasses) of water, 30 minutes before each meal. not during. not after. before. the 30 minute window is important because it gives the water time to reach the stomach and activate the stretch receptors before food arrives. room temperature or cold. consistency matters more than temperature
the most effective weight loss protocol with clinical evidence behind it is free, available in every kitchen on earth, and takes 10 seconds to implement. the $300 billion diet industry exists because people would rather buy complexity than drink water before dinner
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Once rapidly fatal diseases without approved therapeutic options, systemic amyloidoses are now highly treatable.
A new Review summarises treatment advancements and future directions in systemic light chain and transthyretin amyloidosis: spkl.io/60117Khwv
ALT Human body with annotations showing potential organs or systems involved by AL or ATTR amyloidosis. Red colour indicates organs or systems mostly or uniquely involved by AL amyloidosis. Green colour indicates those mostly or uniquely involved by ATTRwt amyloidosis. Blue colour indicates sites of clinical presentation common to both. AL=light chain amyloidosis. ATTR=transthyretin amyloidosis. ATTRv=transthyretin amyloidosis variant. ATTRwt=transthyretin amyloidosis wild-type. *Also common in ATTRv. Copyright: 2026 Elsevier Ltd. All rights are reserved.
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Boredom activates the brain’s default mode network.
Crucial for creativity and fostering a sense of self.
Boredom is a luxury in a world with constant overstimulation.
This quoted post is unavailable.
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A 12-lead ECG can do more than diagnose ventricular tachycardia (VT). It can also help predict where the arrhythmia exits the ventricle, guiding catheter ablation before the procedure begins.
A practical approach:
Start with the limb leads to estimate the VT exit site:
🟨 Septal
⬜ Superior
🟩 Inferior
🟥 Lateral
Next, examine the precordial leads (V1–V6) to determine whether the exit is:
🟪 Basal
🟧 Mid-ventricular
🟦 Apical
Why this matters:
- The initial QRS vector during VT points away from the exit site.
- QRS morphology helps narrow the region where the reentry circuit exits the myocardium.
- Reviewing the clinical VT ECG before ablation improves procedural planning and mapping efficiency.
Prior myocardial infarction also influences VT morphology:
- Anterior infarction (LAD territory) produces characteristic anterior scar-related VT patterns.
- Lateral infarction (LCx territory) results in distinct lateral exit morphologies.
- Inferior infarction (RCA territory) generates different inferior scar-related VT patterns.
If the clinical VT ECG is unavailable, ICD electrograms and pace mapping can help confirm the VT mechanism and estimate the catheter's proximity to the exit site during the procedure.
Reference: Zipes DP, Jalife J. Cardiac Electrophysiology: From Cell to Bedside, Chapter 86.
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For treatment and outcomes for cancer, the tumor microenvironment (TME) is pivotal, but we've never had a non-invasive way to assess it. Until now, a blood test breakthrough! (<-a term I use sparingly)
Pictured below, schematically, the TME surrounds the cancer cells and consists of immune cells, blood vessel (endothelial) cells, fibroblasts and matrix
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Emerging Therapies to Lower Lipoprotein(a) and the Current Clinical Trials Landscape: RNA-Therapeutics and Beyond
☝️The Future of Lipoprotein(a): From Risk Marker to Therapeutic Target
1️⃣ RNA-based therapies (antisense oligonucleotides and siRNA) consistently achieve 80–100% reductions in circulating Lp(a).
2️⃣ Muvalaplin, the first oral small-molecule inhibitor of Lp(a) assembly, represents an exciting non-RNA therapeutic strategy.
3️⃣Multiple Phase 3 cardiovascular outcome trials (HORIZON, OCEAN(a), ACCLAIM-Lp(a), MOVE-Lp(a)) are underway and will determine whether lowering Lp(a) translates into fewer cardiovascular events.
👉Until these results are available, measuring Lp(a) remains essential for cardiovascular risk stratification and optimization of LDL-C lowering.
👉The next few years may redefine residual cardiovascular risk management, shifting Lp(a) from a risk marker to a treatable
therapeutic target.
🔓🔗Open access lipidjournal.com/article/S19…
@LipidJournal
@society_eas
@nationallipid
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🫀Un estudio en Circulation 2026 muestra que una reducción del 10% en la grasa visceral mediante cambios en el estilo de vida se asoció con un 28% menos riesgo de desarrollar diabetes tipo 2 hasta 10 años después, incluso con recuperación parcial del peso.
ALT https://doi.org/10.1161/CIRCULATIONAHA.125.079009
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CRISPR functional genomics uncovers a new RNA dependency in triple-negative breast cancer.
A new Journal of Advanced Research study combines TNBC-focused CRISPR deletion screening, antisense oligonucleotides, transcriptomics, proteomics, and organ-on-chip models to identify TPL1 (TNBC Promoting LncRNA 1) as a previously uncharacterized regulator of tumor growth and invasion.
Key findings
🧬 Genome-scale CRISPR-del screen identifies TPL1
The authors developed a CRISPR-Cas9 promoter-deletion library targeting 1,029 TNBC-enriched lncRNAs across two TNBC cell lines.
Among recurrent fitness hits, TPL1 emerged as one of the strongest candidate lncRNA dependencies.
🔬 TPL1 is required for aggressive TNBC phenotypes
ASO-mediated TPL1 suppression significantly reduced:
• cell proliferation
• colony formation
• 3D organoid growth
• organ-on-chip invasion
across multiple TNBC models, supporting a functional role beyond the original CRISPR screen.
📈 Highly expressed in clinically aggressive TNBC
TPL1 expression was elevated in TNBC tumors and was highest in the basal-like immune-suppressed (BLIS) subtype, suggesting potential clinical relevance in aggressive disease.
🧭 Multi-omics links TPL1 to adhesion and PI3K signaling
Integrated RNA-seq and DIA proteomics demonstrated coordinated suppression of pathways involved in:
• extracellular matrix–receptor interaction
• focal adhesion
• PI3K–AKT signaling
• cell migration
• invasion
after TPL1 knockdown.
🧩 Potential regulatory mechanisms
Multiple orthogonal analyses—including protein microarrays, RNA localization, public TLC-CLIP datasets, RNA-binding predictions, and miRNA network analysis—suggest that TPL1 may function through both:
• RNA-binding protein-associated regulation (EIF4B, TARBP2, TLE5, RAN)
• candidate ceRNA-like miRNA networks
These mechanisms remain hypothesis-generating and require direct biochemical validation.
Why this matters
Most cancer-associated lncRNAs remain functionally unexplored.
This study provides a scalable framework for functional lncRNA discovery using CRISPR deletion screening, while identifying TPL1 as a promising RNA-targetable vulnerability in triple-negative breast cancer.
The combination of CRISPR functional genomics, ASO validation, transcriptomics, proteomics, and advanced organ-on-chip assays demonstrates a powerful pipeline for prioritizing non-coding therapeutic targets.
Citation
Elango R. et al. Functional CRISPR screens reveal TPL1 lncRNA as a regulator of triple-negative breast cancer hallmarks. Journal of Advanced Research (2026). DOI: 10.1016/j.jare.2026.07.006
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ROS is a double-edged sword in cancer.
A comprehensive Journal of Advanced Research review highlights how moderate ROS fuels tumor initiation, metastasis, immune evasion, and therapy resistance, while excessive ROS overwhelms antioxidant defenses to induce apoptosis, ferroptosis, and other cancer cell death programs.
Key insights:
🧬 ROS promotes cancer by activating NF-κB, PI3K/AKT, HIF-1α, remodeling the tumor microenvironment, and suppressing antitumor immunity.
⚔️ Cancer cells adapt through the NRF2–KEAP1, GPX4–GSH, and thioredoxin antioxidant systems, creating therapeutic vulnerabilities that can be exploited.
💊 ROS modulation enhances multiple treatment modalities: • Ferroptosis induction (GPX4 inhibition) • Radiotherapy & chemotherapy • Photodynamic/sonodynamic therapy • Overcoming TKI resistance by disrupting redox adaptation
🧪 An emerging concept is precision redox medicine—using mitochondrial redox signatures and digital biomarkers to stratify patients and tailor ROS-targeted interventions rather than applying uniform antioxidant or pro-oxidant strategies.
📈 Future directions include: • Tumor-specific ROS modulation • Combination therapies with immunotherapy • Targeting NRF2-dependent resistance • Mitochondrial biosensors for personalized treatment selection
Rather than simply "reducing oxidative stress," the future of oncology may lie in precisely controlling where, when, and how much ROS is generated to selectively eliminate cancer while sparing normal tissue.
📄 ROS as a powerful instrument for the advanced cancer prevention and management: Facts and outlook
Journal of Advanced Research (2026)
DOI: 10.1016/j.jare.2026.07.002
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Science behind the Study: Physiological Assessment of Coronary Artery Disease nej.md/4xUKlGx
#Cardiology
ALT A box titled "Key Concepts" with sections on "Fractional flow reserve (FFR)," "Fractional flow reserve derived from coronary angiography (FFRangio)," and "Instantaneous wave-free ratio (iFR)." Each section includes detailed descriptions of these terms. The background features a decorative border with medical and scientific designs.
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In a cluster-randomized trial involving patients having major noncardiac surgery, tranexamic acid reduced the need for red-cell transfusion during hospitalization and was noninferior to placebo for venous thromboembolism within 90 days. Full TRACTION trial results and Research Summary: nej.md/4e8QKF4
ALT This image is from a Research Summary published in the New England Journal of Medicine about a study on tranexamic acid in major noncardiac surgery. It includes a diagram of a blood bag labeled "Red-cell transfusion" and graphics of syringes labeled "Tranexamic Acid" and "Placebo" with participant numbers: N = 4156 and N = 4117 respectively. It also lists patient details: 8273 adults, median age 64 years, with 53% women and 47% men. There is a prompt at the bottom to read the full Research Summary at NEJM.org.
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Currently approved mRNA vaccines are safe and effective at preventing infectious diseases, with promise for future disease prevention and treatment, new review confirms.
Read more: spkl.io/601671q3i
ALT Figure 1: Schematic of mRNA lipid nanoparticle components, mechanism of action, biodistribution, and expression and clearance timeline for mRNA vaccines. LNP=lipid nanoparticle. PEG=polyethylene glycol. Copyright: 2026 Elsevier Ltd. All rights reserved.