Johannes W. Dietrich boosted
SPINA Team

After intensive internal testing, the release candidate 1 of the #SPINA_Carb app is available. This is the "sister" app for #SPINA_Thyr, and it is provided for purposes of testing.

sourceforge.net/projects/spina

doi.org/10.5281/zenodo.1524962

doi.org/10.5281/zenodo.1524962

Screenshot of SPINA Carb Release Candidate 1 for macOS
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Johannes W. Dietrich

The new model can not only explain why primary thyroid disorders act as cardiovascular risk factors but also why chronic stress and type 2 allostatic load increase the hazard for adverse outcomes.

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Johannes W. Dietrich

Interestingly, both subclinical and predict . The free thyroxine (FT4) concentration is more associated with the HR for cardiovascular events than thyrotropin (TSH) levels. Our observations yield an integrated model including psychosocial and somatic mechanisms.

An integrated model for the association between thyroid homeostasis and major cardiovascular events. In the dyshomeostatic type of thyrogenic arrhythmia elevated FT4 concentration, caused by primary thyrotoxicosis, increases the risk for severe arrhythmia as a major cause for cardiovascular mortality. The TSH concentration is reduced in this case, represented by the left, declining, branch of the U-shaped relation between TSH level and risk (A). In the allostatic type, mainly caused by type 2 allostatic load and genetic traits, the set point of thyroid homeostasis is raised, resulting in increased TSH and FT4 concentration and subsequently elevated risk for arrhythmia. This situation is mirrored in the right, rising, branch of the relation between TSH concentration and cardiovascular risk (B). In any case, elevated concentrations of T3, T4 and other T3-agonistic thyroid hormones increase the sensitivity to catecholamines and sympathetic signaling (via upregulated expression of beta1 and beta2 adrenoceptors), thereby contributing to reduced stress tolerance. SPINA-GT, “gain of thyroid,” i.e., thyroid’s secretory capacity.
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Johannes W. Dietrich boosted
SPINA Team

Calculating #SPINA-GT is useful in paediatrics, as recently shown in a research paper by the Medical School of Patras.

SPINA-GT is significantly reduced in subclinical hypothyroidism and even in the upper 2 quartiles of normal TSH.

pubmed.ncbi.nlm.nih.gov/402304
doi.org/10.3389/fendo.2025.136

Box plots showing SPINA GT actual vs predicted values (a) in all euthyroid children divided in groups by quartiles of TSH values and (b) in children with normal TSH in the upper 2 quartiles and children with mild and severe SH (**P < 0.001, *P<0.01).
Table: TSH concentrations (min and max) in euthyroid (by quartiles) and children with SH and their corresponding SPINA-GT value (median and mean) along with the frequency of thyroid antibody positivity.
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Johannes W. Dietrich

hormones profoundly impact the system. They act at all levels, ranging from the tier of ion currents over cellular processes to the macroscopic levels of myocardial tissue and even the whole organism.

doi.org/10.3389/fcvm.2022.9429

pubmed.ncbi.nlm.nih.gov/360461

Thyroid hormone signalling involves four different mechanisms. T4 is a prohormone with respect to genomic signaling, but a true fast-acting hormone regarding type 4 action (which is inhibited by the iodothyroacetate TETRAC). Genomic action (type 1, type 2 and mitochondrial signaling) occurs on a slow time scale, whereas non-genomic effects (type 3 and type 4 signaling) represent a fast response (A). Thyroid hormone receptors (THR) usually act as heterodimers. Without thyroid hormone bound they block the transcription together with corepressors. Iodothyronines displace the corepressors and stimulate gene expression together with coactivators (B). Tissue specific distributions of THRs further contribute to the diversity of signaling patterns in the organism (C). AF-1, activation function 1; AF-2, activation function 2; D2, type 2 deiodinase; DBD, DNA-binding domain; HAT, histone acetyl-transferase; HDAc, histone deacetylase; LBD, ligand-binding domain; RXR, retinoid X receptor; TRE, thyroid-hormone response element.
Thyroid hormones have a profound effect on the intracellular processes of rhythm generation. The figure shows mechanisms of rhythm generation in cardiomyocytes based on a model by Maltsev et al. Two loops, an external membrane loop and an internal calcium loop, independently ensure the generation of impulses. Therefore, they provide some redundancy, but they are also intertwined at the stage of slow L-type Ca2+ current (ICaL) activation. Thyroid hormone signalling can modulate both loops simultaneously via interfaces at several sites, and direct myocardial effects of TSH are largely opposing. gK, ionic conductance for K+; INCX, Na+/Ca2+ exchange current; ICaT, T-type Ca2+ current; If , hyperpolarisation-activated “funny” current; IK, voltage-gated K+ current; Ist , sustained non-selective current; Ito, transient outward potassium current; LCR, local Ca2+ release; SERCA, sarcoendoplasmic reticulum Ca2+-ATPase; SR, sarcoplasmic reticulum.
Selected mechanisms of arrhythmogenesis by thyroid hormones at the cellular level. T3 (and other active thyroid hormones) upregulate the gene expression of beta1 and beta2 adrenoceptors via classical genomic signaling, but downregulate protective beta3 adrenoceptor expression. The transcription of critical genes for the formation of gap junctions is downregulated as well. Potassium channels are regulated via classical type 1 signaling and via non-genomic effects (type 4 action) as well. Purple arrows indicate the effects of gene expression (transcription, translation and associated processing steps), green arrows visualize the impact of T3-agonistic thyroid hormones.
On a macroscopic level, elevated concentrations of thyroid hormones promote arrhythmia by slowing down electrical conduction and reducing the effective refractory period. (A,B) Simplified model of the effects of thyroid hormone signalling facilitating disorders of impulse conduction. Iodothyronine action reduces both the effective refractory period (ERP) and the conduction velocity (θ). As a consequence, the wavelength of excitation λ = ERP x θ may get shorter than the dimensions of a potential re-entry circuit, thus giving rise to re-entrant tachycardia.
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Johannes W. Dietrich boosted
TRURL Team

#TRURL G has been updated to version 1.2.1. This is a recommended bug-fix release that addresses an issue with the erroneous display of small numbers and makes the roll-down feature more HP-like.

TRURL is available from trurl.sf.net.

Screenshot of TRURL G 1.2.1 on macOS 13.7
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Johannes W. Dietrich

The system is sensitive to hormones. Even mild deviations of the free concentration from a (probably individual) optimum confer a significantly increased risk for (major adverse cardiovascular events).

doi.org/10.3389/fcvm.2022.9429

pubmed.ncbi.nlm.nih.gov/360461

Forrest plots showing the hazard ratio for major adverse cardiovascular events (MACE, A) and cardiovascular death (CVD, B) in relation to TSH concentration
Forrest plots showing the hazard ratio for MACE (A) and CVD (B) in relation to FT4 concentration
Forrest plots showing the hazard ratio for inclusive MACE (A), study-specific MACE (B) and CVD (C) in subclinical hypothyroidism
Forrest plots showing the hazard ratio for MACE (A,B) and CVD (C) in subclinical hyperthyroidism
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Johannes W. Dietrich boosted
SPINA Team

#Hidradenitis suppurativa (acne inversa) is linked to #diabetes mellitus. In the affected, #SPINA_GR is reduced and not compensated by #SPINA_GBeta resulting in low #SPINA_DI. This phenomenon may be mediated by inflammation, as shown by ties to #haptoglobin.

pubmed.ncbi.nlm.nih.gov/402175

Table showing endotypes of insulin-glucose homeostasis in patients with hidradenitis suppurative (HS or acne inversa) and different expressions of haptoglobin concentration. In persons with HS and a high haptoglobin concentration, insulin sensitivity (SPINA-GR) and beta-cell function (SPINA-GBeta) are similar but combine to provide a reduced disposition index (SPINA-DI).
Plot of SPINA-GBeta versus SPINA-GR in patients with HS and controls: The majority of patients with HS and diabetes are faced with rather low insulin sensitivity and a lack of dynamic compensation via pancreatic beta-cell function, resulting in a reduced disposition index.
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Johannes W. Dietrich boosted
Scientific Pascal

MacPaint was a revolutionary app that demonstrated the capabilities of early #Macintosh computers. Jeffrey Starr reviews its source code in his blog. The code in #Pascal and assembly language, while still in old procedural style, is an example of good programming practice.

ztoz.blog/posts/macpaint-sourc

Screenshot of MacPaint 1.5 (1985)
MacPaint screenshot with Japanese Lady (1984)
Source code of the HVContrain procedure: PROCEDURE HVConstrain(VAR newPt: Point); VAR dh,dv: INTEGER; BEGIN IF shiftFlag THEN { constrain to horiz or vert } BEGIN IF hConstrain AND vConstrain THEN { still chosing direction } BEGIN dh := ABS(newPt.h-ptConstrain.h); dv := ABS(newPt.v-ptConstrain.v); IF (dh > dv) AND (dh > 1) THEN vConstrain := FALSE; IF (dv > dh) AND (dv > 1) THEN hConstrain := FALSE; END; IF hConstrain THEN newPt.v := ptConstrain.v; { horiz } IF vConstrain THEN newPt.h := ptConstrain.h; { vert } END; END;
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Johannes W. Dietrich

Medical treatment of , i.e. due to overproduction of hormone, remains a challenge. We developed a new dosage methodology based on model predictive control (MPC), which is faster and more stable than the usual trial-and-error approach. doi.org/10.1016/j.ifacol.2025.

Fig. 1. Simplified block diagram of the pituitary-thyroid feedback loop. The thyroid produces the hormones T3 and T4. On the one hand, this process is stimulated by TSH, a hormone secreted from the pituitary. On the other hand, this process is inhibited by Methimazole (MMI), an antithyroid agent (i.e., a medication), which constitutes the control input in this work. The hormone T4 gets converted into T3 by the enzymes 5’-deiodinase type I (D1) and 5’-deiodinase type II (D2). Finally, TRH (which is a natural hormone, and not a medication) stimulates the production of TSH.
Fig. 2. Illustration of the guidelines given by the American Thyroid association (ATA) (Ross et al., 2016). The treating physician may encounter many difficulties to select one precise dosage using these (rather vague) recommendations.
Fig. 3. Simulation results of an exemplary treatment based on the guidelines introduced in Ross et al. (2016). We apply the mean medication dosage for each interval, e.g., if the concentration of FT4 (which is proportional to T4) is within 27−42 pmol/L, we apply 7.5 mg. As disturbances, we consider forgotten dosages and measurement noise as explained in Section 3.
Fig. 4. Course of the hormone concentrations and the corresponding MMI dosages that are taken orally once per day. The dosages are determined by the MPC scheme introduced in Subsection 2.2. As explained in Section 3, we consider forgotten dosages, a model-plant mismatch, and some measurement noise as disturbances.
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Johannes W. Dietrich

Diabetes mellitus is common in hidradenitis suppurativa (acne inversa). Affected persons are faced with low insulin sensitivity (-GR) and a lack of dynamic compensation via pancreatic beta-cell function (-GBeta), resulting in a reduced disposition index (-DI).

doi.org/10.3390/jcm14072145

Measured and calculated biomarkers for insulin–glucose homeostasis in patients with hidradenitis suppurativa (acne inversa, HS) and controls. Reconstructed insulin receptor gain (SPINA-GR) is reduced in HS, and the secretory capacity of pancreatic beta cells (SPINA-GBeta) is compensatorily increased.
Parameters of insulin–glucose homeostasis in patients with HS and with and without diabetes mellitus. In persons affected by both HS and diabetes mellitus, reduced SPINA-GR is insufficiently compensated by SPINA-GBeta, resulting in reduced static disposition index (SPINA-DI) and diabetes.
Parameters of insulin–glucose homeostasis in patients with HS and with and without diabetes mellitus. In persons affected by both HS and diabetes mellitus, reduced SPINA-GR is insufficiently compensated by SPINA-GBeta, resulting in reduced static disposition index (SPINA-DI) and diabetes.
In persons with HS and a high haptoglobin concentration, insulin sensitivity (SPINA-GR) and beta-cell function (SPINA-GBeta) are similar but combine to provide a reduced disposition index (SPINA-DI).
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Johannes W. Dietrich

Multiple studies have proven the impact of ​s, e.g. and , on . It was unknown, however, that these effects depend on whether or not the included persons are fasting.

pubmed.ncbi.nlm.nih.gov/398266

doi.org/10.1016/j.envres.2025.

Associations between urinary chemicals and thyroid hormones, GD, or GT: results from single-exposure models. Group 1 (n = 340; n = 339 for TSH) indicates the non-fasting group, Group 2 (n = 254; n = 252 for TSH) indicates the fasting group, and Total indicates the total population, including both Group 1 and Group 2 (n = 594; n = 591 for TSH). Age, BMI, urinary creatinine, and education level were adjusted, and the group by fasting status was further adjusted in the total population. *p < 0.05; #p < 0.1. Phthalate metabolites measured in both groups included mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-(2-ethyl-5-oxohexyl)phthalate (MEOHP), mono(5-carboxy-2-ethylpentyl) phthalate (MECPP), mono-n-butyl phthalate (MnBP), and MBzP. For parabens, methylparaben (MeP), EtP, and propylparaben (PrP) were measured.
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Johannes W. Dietrich

Weltweit und gleichzeitig radikalisieren sich Teile der Bevölkerung und driften nach rechts. Was ist die Ursache?

Neben maschineller Probaganda könnte auch der negative -Effekt eine Rolle spielen, eine Intelligenzabnahme durch endokrine ​en.

blog.endokrinologie.net/intell

Visualisierung des negativen Flynn-Effekts. Umweltgifte im Sinne von endokrinen Disruptoren behindern die Wirkung von Schilddrüsenhormonen in zahlreichen Organen und führen zu zu einer längerfristigen Intelliganzabnahme. Quelle: Demeneix B, Slama R (2019), Endocrine Disruptors: From Scientific Evidence to Human Health Protection. Study, requested by the European Parliament Committee on Petitions. Policy Department for Citizens‘ Rights and Constitutional Affairs. Directorate General for Internal Policies of the Union. PE 608.866. http://www.europarl.europa.eu/RegData/etudes/STUD/2019/608866/IPOL_STU(2019)608866_EN.pdf
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Johannes W. Dietrich boosted
SPINA Team

Growing evidence supports a role of sensorimotor and autonomic #neuropathy in #syndrome_T or #SORSHOT, i.e. reduced quality of life in treated #hypothyroidism. #SPINA_GT and #SPINA_GD predict nerve function and depression.

pubmed.ncbi.nlm.nih.gov/388117

doi.org/10.1038/s41598-024-631

Scatterplots showing a significant correlation of functional parameters of thyroid homeostasis (SPINA-GT and SPINA-GD) with the mechanical pain sensitivity (MPS) of QST (A), respiratory arrhythmia in HRV analysis (B) and depression percentiles in HADS (C).
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Johannes W. Dietrich boosted
SPINA Team

Again, a study showed a strong influence of endocrine disruptors on #thyroid homeostasis. Exposure to butylparaben significantly reduces #SPINA-GD, whereas ethylparaben slightly increases #SPINA_GT in pregnancy.

pubmed.ncbi.nlm.nih.gov/398894

doi.org/10.1016/j.ecoenv.2025.

Figure (Forest plot): Changes in the levels of thyroid hormone indicators in relation to a 1 ng/mL increase in paraben exposure across trimesters. Data are presented in terms of adjusted regression coefficient and 95% confidence interval values. Exposure to butylparaben significantly reduces #SPINA-GD, whereas ethylparaben slightly increases #SPINA_GT in pregnancy, depending on the trimenon.
Forest plot: Results of generalized estimating equation–based analyses of the associations between thyroid hormones and urinary parabens in pregnant women (N = 207). The effect on SPINA-GD is different from and stronger than that on T3/T4 ratio.
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Johannes W. Dietrich

About 10% of hypothyroid patients have reduced quality of life despite normal TSH concentration under therapy with levothyroxine (L-T4). A new randomised, double-blind trial demonstrated better QoL under L-T4 + L-T3 compared to L-T4 alone.

pubmed.ncbi.nlm.nih.gov/398652

doi.org/10.1186/s12902-025-018

Table: Changes in SF-36V1 scores at baseline and 6 months. Physical functioning, general health perception and mental health improve under L-T4 + L-T3 combination therapy significantly better than under monotherapy with L-T4 alone.
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Johannes W. Dietrich

Teilnehmer:innen gesucht! Klinische Studie zur Verbesserung der bei mellitus Typ 1.

klinikum-bochum.de/fachbereich

Teilnehmer gesucht! Klinische Studie zur Verbesserung der Insulintherapie bei Typ 1 Diabetes
Sind Sie eine Person mit Typ 1 Diabetes und interessiert daran, die Auswirkungen von verschiedenen Insulinpräparaten auf Ihren Blutzucker nach den Mahlzeiten zu erforschen? Haben Sie eventuell sogar Probleme mit Blutzuckerschwankungen nach der Mahlzeit? Wenn ja, könnten Sie der Schlüssel zu einer Personalisierung der Insulintherapie bei Menschen mit Typ 1 Diabetes sein.
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Johannes W. Dietrich

Digitale Zwillinge in der Endokrinologie: Der Weg zu einer prädiktiven und personalisierten Medizin. 🧪🩺

blog.endokrinologie.net/digita

The digital twin framework nach Serani Rad et al. 2024 [PMID 38672986]. Aus Daten die von einer/einem echten Patientin/Patienten gewonnen werden (links) wird eine virtuelle Repräsentation (digitaler Zwilling, mitte) erstellt, aus der dann sinnvolle Schlussfolgerungen für eine personalisierte Therapie (rechts) gezogen werden können.
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Johannes W. Dietrich

Hintergrundartikel zum Thema in diabetologie-online:

diabetologie-online.de/a/pilot

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Johannes W. Dietrich

​es mit nichtinvasiver , ohne Stich, zuverlässig und günstig? Zu schön, um wahr zu sein! Untersuchungen des Instituts für in Ulm legen den Betrug offen. Selbst auf einer Banane wird ein "gemessen". 🩺🧪

ifdt-ulm.de/fileadmin/website/

Betrug mit Smartwatches: Gemessene und simulierte Glukoseverläufe auf zwei importierten Smartwatches ohne Zulassung als Medizinprodukt (orage und blaue Kurven) verglichen mit gemessenen Werten aus einem CGM-Sensor (grüne Kurve). Die Werte der Smartwatches sind jeden Tag fast identisch und weichen von denen des Sensors teils sehr stark ab. Selbst auf einer Banane wird ein "Blutzuckerverlauf" angezeigt.
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