Aging is multi-causal, yet its molecular hallmarks may converge on a few upstream integrating nodes. We advance the hypothesis that chronic, largely mutation-independent overactivation of the DNA damage response (DDR) is one such node, dysregulating the cell's intact guardian pathways-the tumor-suppressor networks and their negative regulators-to induce senescence, deplete stem-cell pools, and drive inflammaging. Unlike cancer, where mutations inactivate these guardians, aging more often reflects functional dysregulation of wild-type pathways, either chronically overactivated (p53, p16INK4a) or epigenetically silenced (SIRT1, FOXO3, NRF2, Klotho). That the very programs guarding against cancer can, when chronically engaged, come to drive aging we term the guardian paradox. We organize 16 candidate axes-which we term the aging axis-across three evidence tiers, mapped onto the hallmarks of aging, outlining for each a conceptual diagnostic signature and an illustrative restoration strategy, with all numeric biomarker bands and vector details confined to the Supplementary Information as non-clinical placeholders. We set this DDR-integrator hypothesis against mitochondria-, proteostasis-, and reprogramming-first models and pre-specify longitudinal, mediation, and head-to-head tests that could support, demote, or refute it. No integrated human interventional data yet exist; we therefore present a falsifiable research agenda, not a therapeutic protocol.

Lupus nephritis (LN) with a membranoproliferative pattern is an uncommon but recognized renal manifestation of systemic lupus erythematosus (SLE). While autoimmune myelofibrosis (AMF) has been described in association with SLE, the coexistence of primary myelofibrosis (PMF) with this pattern of LN has not been previously documented. We report a 50-year-old man with JAK2-positive PMF, undifferentiated connective tissue disease (UCTD), and Stage 3b chronic kidney disease who developed nephrotic syndrome and worsening kidney function. Initial serologic evaluation revealed positive antinuclear antibody (ANA), low serum complement C3, and negative antidouble-stranded DNA (anti-dsDNA) antibodies. Kidney biopsy demonstrated a membranoproliferative pattern of injury with mesangial and subendothelial immune complex deposits staining for IgM and C1q. Subsequent testing revealed high-titer anticardiolipin IgM antibodies. The patient met the 2019 EULAR/ACR classification criteria for SLE. Induction therapy with high-dose prednisone and mycophenolate mofetil resulted in a partial remission, with stabilization of renal function on follow-up. To our knowledge, this is the first reported case of LN with a membranoproliferative pattern of injury in a patient with PMF. The case underscores the diagnostic value of kidney biopsy in uncovering occult systemic autoimmune disease in patients with myeloproliferative neoplasms (MPNs), particularly when the clinical and demographic profile is atypical for SLE.

Takayasu arteritis is an idiopathic vasculitis that typically involves the aorta and its major branches. It is more common in women and has the highest prevalence in Asia. Imaging studies are crucial for establishing the diagnosis and for determining the extent of the disease. We present the case of a 47-year-old man who presented with a complaint of anuria and generalized weakness for the last three days. He reported a history of generalized abdominal pain for the last two weeks. His vital signs were within normal limits, but the systolic blood pressure in the lower limb was lower by 60 mmHg compared with that of the upper limb. Notably, the pulses were very faint on palpation. Laboratory investigations revealed deranged renal function parameters. Ultrasound examination showed increased renal parenchymal echogenicity bilaterally with elevated peak systolic velocity of the main renal artery on spectral Doppler. Further investigation by computed tomography demonstrated near-complete thrombosis of the abdominal aorta distal to the origin of the celiac artery and extending to the common iliac arteries with the involvement of bilateral renal arteries. Immunological investigations, including antinuclear antibody (ANA), double-stranded deoxyribonucleic acid (dsDNA), cyclic antineutrophil cytoplasmic antibody (c-ANCA), and perinuclear antineutrophil cytoplasmic antibody (p-ANCA), revealed negative results. However, the positron emission tomography showed markedly diffuse and circumferential increased uptake in the walls of the aorta, subclavian arteries, and femoral arteries. The patient underwent successful endovascular treatment with catheter-directed thrombolysis. High clinical suspicion is required to identify renal artery thrombosis since the clinical symptoms are non-specific. Early diagnosis is crucial to allow for prompt therapeutic interventions.

Post-infectious glomerulonephritis (PIGN) is an injury to glomerules mediated by the immune response after infection, and it is commonly seen in children. However, the elderly with immunocompromised conditions are at higher risk of developing PIGN after a recent infection. A 74-year-old female presented to the ER with a history of severe, sharp, on and off left flank pain for two days. Initial laboratory results workup were suggestive of acute kidney injury with no obvious reason. Dialysis was required as the renal function was deteriorating. Serologic test was negative for ANA (anti-neutrophil antibodies), C-ANCA (anti-neutrophil cytoplasmic antibodies), and P-ANCA (perinuclear anti-neutrophil cytoplasmic antibodies). C3 level was low, and anti-streptolysin O titer was high. Renal biopsy was performed. With reference to the clinical and histological examination, she was diagnosed with PIGN and diabetic nephropathy. After six months, the renal function was improving gradually until hemodialysis was stopped, and the PermcathTM (Medtronic) was removed with a creatinine level of 120 µmol/L. The elderly diabetic female developed PIGN with crescents that required dialysis, and dialysis was stopped after six months with good prognosis. Since PIGN is a very rare entity, the suspicion of PIGN in the elderly with acute kidney injury should be raised after a history of upper respiratory tract or skin infection.

This study aimed to assess the level of knowledge, attitudes, and practices (KAP) concerning malaria and malaria prevention among rural populations residing in the southwestern region of Saudi Arabia. This was a household-based cross-sectional survey, using structured questionnaire that was developed and distributed among households selected randomly from 19 villages (clusters) located in a southwestern region of Saudi Arabia, north of the border with Yemen. The data collected were analyzed using SPSS version 20. A majority of respondents (98.4%) reported that they had heard about malaria, but only 21.7% reported that they had sufficient information about the disease. Surprisingly, the most popular source of information was the internet and social media (proportion responding positively in parenthesis) (25.5%), followed by family (21.7%), while information from health facilities contributed only 12.4%. A majority of respondents were aware that malaria is a communicable (89.1%) and deadly (70%) disease; however, only 30.2% of the respondents responded that malaria is a treatable disease. Almost all of the aware respondents (97.5%) were inclined to seek treatment from health facilities, and 63.2% preferred to seek treatment within 24h of presenting with symptoms. Regarding personal precautions, the most common practice adopted by respondents was indoor residual spraying IRS (47.3%), followed by anti-mosquito spraying (29.8%), mosquito bed nets (13.2%) and combined anti-mosquito sprays and nets on windows (4.7%). This KAP study did not show any statistically significant differences in KAP due to age; however the practices of preventive measures against malaria differed significantly by nationality (Saudi versus non-Saudi). We conclude that most populations living in the villages have an acceptable level of knowledge and awareness about malaria and seek timely treatment. However, the positive attitudes and practices in relation to personal protection and prevention measures against malaria require marked improvement. The obvious gap between the knowledge and practice related to malaria prevention requires innovative strategies based on local evidence that well suits the local circumstances to promote and encourage the adoption and practice of personal protective measures.

Nowadays, there is increasing interest in natural antioxidants from food by-products. Astaxanthin is a potent antioxidant and one of the major carotenoids in crustaceans and salmonids. An ultra-high pressure liquid chromatographic method was developed and validated for the determination of astaxanthin in shrimp by-products, and its migration from new packaging materials to food simulants was also studied. The method uses an UPLC® BEH guard-column (2.1 × 5 mm, 1.7 µm particle size) and an UPLC® BEH analytical column (2.1 × 50 mm, 1.7 µm particle size). Chromatographic separation was achieved using a programmed gradient mobile phase consisting of (A) acetonitrile-methanol (containing 0.05 m ammonium acetate)-dichloromethane (75:20:5, v/v/v) and (B) ultrapure water. This method was evaluated with respect to validation parameters such as linearity, precision, limit of detection, limit of quantification and recovery. Low-density polyethylene films were prepared with different amounts of the lipid fraction of fermented shrimp waste by extrusion, and migration was evaluated into food simulants (isooctane and ethanol 95%, v/v). Migration was not detected under the tested conditions.

Education: 6. Schools of nursing should address decision-making within their curriculum related to the impact that fatigue and the habitual The American Nurses Association (ANA) takes the position that, regardless of the number of hours worked, all registered nurses have an ethical responsibility to carefully consider their level of fatigue when deciding whether to accept any assignment extending beyond their regularly scheduled work day or week, including a mandatory or voluntary overtime assignment.

Adrenaline is the drug of choice for the treatment of anaphylaxis. The indications, available formulations, and rules for prescribing adrenaline for self treatment of anaphylactic reactions in allergic subjects are summarized in this paper. Emergency kits containing adrenaline must be prescribed only to patients with a definite history of anaphylactic reactions or laryngeal oedema. A kit containing Adrenaline DAK 1 mg/ml in a traditional glass ampoule together with a 1 ml syringe and an i.m. cannula is the cheapest solution, and a usable alternative in the patient who after sufficient training feels safe to prepare his own injection. Ana-guard injector is recommended for the allergic adult due to its easy handling and the fact that it contains two doses of adrenaline 0.3 mg. For both children and adults with a low bodyweight, the Epi-Pen automatic injector is recommended. It contains one dose of adrenaline (0.15 or 0.30 mg) and requires no preparation before use. The Adrenalin Medihaler is recommended for the treatment of laryngeal oedema and threatened airway obstruction. Due to the low and unpredictable absorption after inhalation, adrenaline injection is recommended for the treatment of systemic symptoms. Prescribing adrenaline in semi-or automatic injectors requires special permission from the Danish Health Authorities.