rastinza @rastinza@qoto.org

En serio

Por qué la gente envía

Un mensaje de whatsapp, o dos

Por cada frase que escribe

Es desesperante

Podéis usar el punto y seguido

O el punto y aparte

Incluso podéis meter saltos de línea sin signos de puntuación

Pero no hagáis sonar el teléfono de otra persona 20 veces

Por favor

Gracias

Un besi

😘😘

Qualcuno - non ricordo più chi - disse che un chimico è una persona che lega molta della propria vita ad un paio di reazioni incontrate su un libro di testo.

Queste due sono tra le principali che mi hanno procurato dieci anni di stipendio. Poi son finito a fare altro, ma quella è un'altra storia.

cross-posted from: lemmy.bestiver.se/post/821202

spoiler

For more than a century, people have considered Alzheimer’s disease (AD) an irreversible illness. Consequently, research has focused on preventing or slowing it, rather than recovery. Despite billions of dollars spent on decades of research, there has never been a clinical trial of any drug to reverse and recover from AD. A research team from Case Western Reserve University, University Hospitals (UH) and the Louis Stokes Cleveland VA Medical Center has now challenged this long-held dogma in the field, testing whether brains already badly afflicted with advanced AD could recover. The study, led by Kalyani Chaubey, from the Pieper Laboratory, was published online Dec. 22 in Cell Reports Medicine. Using diverse preclinical mouse models and analysis of human AD brains, the team showed that the brain’s failure to maintain normal levels of a central cellular energy molecule, NAD+, is a major driver of AD, and that maintaining proper NAD+ balance can prevent and even reverse the disease. NAD+ levels decline naturally across the body, including the brain, as people age. Without proper NAD+ balance, cells eventually become unable to execute many of the critical processes required for proper functioning and survival. In this study, the team showed that the decline in NAD+ is even more severe in the brains of people with AD, and that this same phenomenon also occurs in mouse models of the disease. While AD is a uniquely human condition, it can be studied in the laboratory with mice that have been genetically engineered to express genetic mutations known to cause AD in people. The researchers used two of these mouse models: One carried multiple human mutations in amyloid processing; the other carried a human mutation in the tau protein. Amyloid and tau pathology are two of the major early events in AD. Both lines of mice develop brain pathology resembling AD, including blood-brain barrier deterioration, axonal degeneration, neuroinflammation, impaired hippocampal neurogenesis, reduced synaptic transmission and widespread accumulation of oxidative damage. These mice also develop the characteristics of severe cognitive impairments seen in people with AD. After finding that NAD+ levels in the brain declined precipitously in both human and mouse AD, the research team tested whether preventing loss of brain NAD+ balance before disease onset or restoring brain NAD+ balance after significant disease progression could prevent or reverse AD, respectively. The study was based on their previous work, published in Proceeding of the National Academy of Sciences USA, showing that restoring the brain’s NAD+ balance achieved pathological and functional recovery after severe, long-lasting traumatic brain injury. They restored NAD+ balance by administering a now well-characterized pharmacologic agent known as P7C3-A20, developed in the Pieper lab. Remarkably, not only did preserving NAD+ balance protect mice from developing AD, but delayed treatment in mice with advanced disease also enabled the brain to fix the major pathological events driven by the disease-causing genetic mutations. Moreover, both lines of mice fully recovered cognitive function. This was accompanied by normalized blood levels of phosphorylated tau 217, a recently approved clinical biomarker of AD in people, providing confirmation of disease reversal and highlighting an objective biomarker that could be used in future clinical trials for AD recovery. “We were very excited and encouraged by our results,” said Andrew A. Pieper, the study’s senior author, a professor at the Case Western Reserve School of Medicine and director of the Brain Health Medicines Center, Harrington Discovery Institute at UH. “Restoring the brain’s energy balance achieved pathological and functional recovery in both lines of mice with advanced Alzheimer’s. Seeing this effect in two very different animal models, each driven by different genetic causes, strengthens the new idea that recovery from advanced disease might be possible in people with AD when the brain’s NAD+ balance is restored.” Pieper also holds the Morley-Mather Chair in Neuropsychiatry at UH and the CWRU Rebecca E. Barchas, MD, DLFAPA, University Professorship in Translational Psychiatry. He serves as psychiatrist and investigator in the Louis Stokes VA Geriatric Research Education and Clinical Center. The results prompt a paradigm shift in how researchers, clinicians and patients can think about treating AD in the future. “The key takeaway is a message of hope—the effects of Alzheimer’s disease may not be inevitably permanent,” Pieper said. “The damaged brain can, under some conditions, repair itself and regain function.” “Through our study, we demonstrated one drug-based way to accomplish this in animal models, and also identified candidate proteins in the human AD brain that may relate to the ability to reverse AD,” Chaubey said. Pieper emphasized that current over-the-counter NAD±precursors have been shown in animal models to raise cellular NAD+ to dangerously high levels that promote cancer. The pharmacological approach in this study, however, uses a pharmacologic agent (P7C3-A20) that enables cells to maintain their proper balance of NAD+ under conditions of otherwise overwhelming stress, without elevating NAD+ to supraphysiologic levels. “This is an important factor when considering patient care, and clinicians should consider the possibility that therapeutic strategies aimed at restoring brain energy balance might offer a path to disease recovery,” Pieper said. This work also encourages new research into complementary approaches and eventual testing in patients, and the technology is being commercialized by Cleveland-based company Glengary Brain Health, which Pieper co-founded. “This new therapeutic approach to recovery needs to be moved into carefully designed human clinical trials to determine whether the efficacy seen in animal models translates to human patients,” Pieper said. “Additional next steps for the laboratory research include pinpointing which aspects of brain energy balance are most important for recovery, identifying and evaluating complementary approaches to Alzheimer’s reversal, and investigating whether this recovery approach is also effective in other forms of chronic, age-related neurodegenerative disease.”

www.cell.com/…/S2666-3791(25)00608-1

Summary: Alzheimer’s disease (AD) is traditionally considered irreversible. Here, however, we provide proof of principle for therapeutic reversibility of advanced AD. In advanced disease amyloid-driven 5xFAD mice, treatment with P7C3-A20, which restores nicotinamide adenine dinucleotide (NAD+) homeostasis, reverses tau phosphorylation, blood-brain barrier deterioration, oxidative stress, DNA damage, and neuroinflammation and enhances hippocampal neurogenesis and synaptic plasticity, resulting in full cognitive recovery and reduction of plasma levels of the clinical AD biomarker p-tau217. P7C3-A20 also reverses advanced disease in tau-driven PS19 mice and protects human brain microvascular endothelial cells from oxidative stress. In humans and mice, pathology severity correlates with disruption of brain NAD+ homeostasis, and the brains of nondemented people with Alzheimer’s neuropathology exhibit gene expression patterns suggestive of preserved NAD+ homeostasis. Forty-six proteins aberrantly expressed in advanced 5xFAD mouse brain and normalized by P7C3-A20 show similar alterations in human AD brain, revealing targets with potential for optimizing translation to patient care.

qualcuno ha idea di PERCHECCAZZO delle credenziali aruba (non è roba mia, è lavoro, ieri stavo cercando di comprare una firma digitale per un associato), che fino a ieri funzionavano perfettamente, stamattina non funzionano più?

boost graditi e ringraziamenti anticipati a tutt*!!

How well does your language work with the Latin script?

(by u/Alias_X_)

Oggi Silvia s'è presentata con un gattino preso al gattile di un paio di mesi.
Io le faccio:" e questo mo de chi è"?
e lei:"è tuo amore, ho pensato che con te sarebbe stato bene......e poi i tuoi figli lo adoreranno".
E gnente, sto coso tutto nero co l'occhi verdi mo vive co me 😂

I'm at an ASD conference. "Using AI to teach social skills." Part of the pitch is that parents of ASD children spend 43 hours/week…. Use AI to teach social skills so you can spend less time with the kids engaging with them socially. FFS

Il sole splende, il lago riluce e piazza Cavour è una festa di colori, coperte e sorrisi che scaldano il cuore!

#VivaVittoria #FarePerDonare #mastouncinetto #uncinetto #crochet

@cafeindy @GustavinoBevilacqua

E al netto del fatto che la crisi economica cominciano a sentirla anche in Germania il fatto che i lavoratori siano pagati molto di più che in Italia a fronte di un costo della vita non tanto più alto (esclusi gli affitti) è il motivo principale per cui a 30 anni è normale avere già due figli.

Stamattina mi girava in testa la "polta infernal" delle streghe del Macbeth di Verdi, così ve la condivido e buongiornissimo...

Questo è il momento.
Su via! sollecite giriam la pentola,
Mesciamvi in circolo possenti intingoli:
Sirocchie, all'opera! l'acqua già fuma,
Crepita e spuma.
(gettando nella caldaia)

I.
Tu, rospo venefico
Che suggi l'aconito,
Tu, vepre, tu, radica
Sbarbata al crepuscolo
Va', cuoci e gorgoglia
Nel vaso infernal.

II.
Tu, lingua di vipera,
Tu, pelo di nottola,
Tu, sangue di scimmia,
Tu, dente di botolo,
Va', bolli e t'avvoltola
Nel brodo infernal.

III.
Tu, dito d'un pargolo
Strozzato nel nascere.
Tu, labbro d'un Tartaro,
Tu, cuor d'un eretico,
Va'dentro, e consolida
La polta infernal.

Estoy seguro de que si ahora alguien va a casa de esta nutricionista encuentra los 4 jinetes de la apocalipsis en su cocina:
Carnes procesadas, bebidas azucaradas, patatas fritas y dulces.
Dejad ya de tocar los cojones con lo que se debe y no se debe tener en casa!

Sandra Purqueras, nutricionista: "Los cuatro productos que nunca deberías traer a tu casa"

https://www.noticiasdenavarra.com/salud/2025/11/07/sandra-purqueras-nutricionista-cuatro-productos-nunca-deberias-traer-a-tu-casa-10315584.html