Dianet

Antiretroviral therapy (ART) initiated in the acute phase of HIV infection (AHI) results in a smaller viral reservoir. However, the impact of early HIV-specific T-cell responses on long-term reservoir dynamics is less well characterized. Therefore, we measured the size of the viral reservoir and functionality of HIV-specific CD8+ T-cell responses after the acute phase at 24 and 156 weeks after ART initiation in people with HIV who started treatment during AHI. A significant reduction in total and defective HIV DNA and a trend toward a reduction in intact HIV DNA were observed between 24 and 156 weeks. Functional CD8+ T-cell responses against HIV peptides Env, Gag, Nef, and Pol were maintained over 3 years after treatment initiation. The proliferative capacity of HIV-specific CD8+ T-cells at 24 weeks of ART was predictive of the degree of reduction in total and defective HIV DNA between 24 and 156 weeks, suggesting HIV-specific CD8+ T-cells may at least partially drive the decline of the viral reservoir. Therefore, enforcing HIV-specific immune responses as early as possible after diagnosis of AHI should be a central focus of HIV cure strategies.

Generative AI (GenAI) is reshaping work, but adoption remains largely individual and experimental rather than coordinated into collaborative work. Whether GenAI can move from individual use to collaborative work is a critical question for future organizations. Journalism offers a compelling site to examine this shift: individual journalists have already been disrupted by GenAI tools; yet newswork is inherently collaborative relying on shared norms and coordinated workflows. We conducted 27 interviews with newsroom managers, editors and front-line journalists in China. We found that journalists frequently used GenAI to support daily tasks, but value alignment was safeguarded mainly through individual discretion. At the organizational level, GenAI use remained disconnected from team workflows, hindered by structural barriers and cultural reluctance to share practices. These findings underscore the gap between individual and collaborative work, pointing to the need to account for organizational structures, cultural norms, and workflow when coordinating GenAI for collaborative work.

Therapeutic plasma exchange (TPE) is an effective treatment for several renal disorders, including renal transplant rejection. However, repeated plasma exchanges can result in various metabolic disturbances and complications. We present a 61-year old male with a medical history of type 2 diabetes, hypertension, successfully treated multiple myeloma, and a post-mortem kidney transplantation 7 months prior to presentation. The patient was hospitalized with an antibody-mediated transplant rejection for which treatment with methylprednisolone, TPE with a 40 g/L albumin solution as a replacement fluid, and intravenous immunoglobulins was initiated. After four TPE treatments, the patient developed gastrointestinal complaints and muscle weakness. Despite daily oral bicarbonate supplementation, laboratory tests revealed a hyperchloremic metabolic acidosis: bicarbonate 11.7 mmol/L, chloride 111 mmol/L, and sodium 138 mmol/L. Metabolic acidosis due to citrate accumulation was ruled out with a normal total-to-ionized calcium ratio. After treatment with intravenous bicarbonate supplementation, the symptoms disappeared. Analysis of the albumin solution showed a chloride concentration of 132 mmol/L. This is the first case that describes severe metabolic acidosis after multiple sessions of TPE with an albumin solution in a patient with impaired renal function. The hyperchloremic metabolic acidosis is the result of administration of large volumes of an albumin solution with high chloride concentrations. Special attention should be paid to the acid-base balance during TPE in patients with impaired renal function. Future research should investigate the incidence of hyperchloremic metabolic acidosis during TPE in patients with impaired renal function.

Fire is one of the governing load cases for design of precast tunnel segments in transit tunnels. As the best practice, a design procedure is provided based on computational fluid dynamics (CFD) simulation of a light-rail train fire and importing CFD results into a two-dimensional coupled thermo-mechanical finite element analysis (FEA). Application of this procedure to a 6-m diameter tunnel made of Fiber-reinforced concrete (FRC) segments is presented. While use of standard fire curves simplifies the design, it can result in overestimation of fire load on segments. Results show that once the actual fire curve of a light-rail train from CFD analysis used together with a coupled thermo-mechanical FEA, more realistic fire loads can be obtained, resulting in an optimized design of FRC segments.

Introduction Limitedinformation exists concerning the clinical significance of histologically confirmed antibody-mediated rejection (h-AMR) without detectable circulating donor-specific antibodies (DSA). In this study, we compared the outcomes of patients with h-AMR according toDSAstatus. Methods A total of 80 kidney transplant (KT) recipients who met the 2018 Banff criteria for h-AMR were included. Clinical and immunological characteristics were evaluated, and outcomes were compared according toDSAstatus after kidney biopsy (KB). Results There were 57 patients who had DSA-positive (+) h-AMR and 23 patients who hadDSA-negative (-) h-AMR. Groups had similar baseline characteristics and time between KT and KB. Concerning histopathological diagnoses/Banff scores,DSA+ patients had higher interstitial fibrosis (ci) and tubular atrophy (ct) (ci+ct) scores and lower arterial hyalinosis (ah) scores compared toDSA- patients. Graft survival (GS) was similar for both groups (64% versus 44% at five years and 44% versus 34% at 10 years).Multivariate analysis revealed the time of KB (less than six months after KT or more than six months after KT) to be associated with GS. A stratified analysis was conducted, targetingDSAstatus according to the time of biopsy. For KB performed less than six months after KT, GS was higher forDSA+ patients at 10 years (66% versus 23%). For KB performed more than six months after KT,DSA- patients had higher GS at 10 years (58% versus 9%). Conclusion Both the timing of AMR diagnosis and DSA status had an impact on AMR outcomes. For patients diagnosed with AMR more than six months after transplantation, GS was worst for those in which circulating DSA were identified. Biopsy specimens from DSA- specimens had higher ct-ci and ah scores.

Hyperphosphataemia is strongly associated with cardiovascular disease and mortality. Recently, phosphate binders (PBs), which are used to bind intestinal phosphate, have been shown to bind vitamin K, thereby potentially aggravating vitamin K deficiency. This vitamin K binding by PBs may offset the beneficial effects of phosphate reduction in reducing vascular calcification (VC). Here we assessed whether combining PBs with vitamin K2 supplementation inhibits VC. We performed 3/4 nephrectomy in rats, after which warfarin was given for 3 weeks to induce vitamin K deficiency. Next, animals were fed a high phosphate diet in the presence of low or high vitamin K2 and were randomized to either control or one of four different PBs for 8 weeks. The primary outcome was the amount of thoracic and abdominal aorta VC measured by high-resolution micro-computed tomography (µCT). Vitamin K status was measured by plasma MK7 levels and immunohistochemically analysed in vasculature using uncarboxylated matrix Gla protein (ucMGP) specific antibodies. The combination of a high vitamin K2 diet and PB treatment significantly reduced VC as measured by µCT for both the thoracic (P = 0.026) and abdominal aorta (P = 0.023), compared with MK7 or PB treatment alone. UcMGP stain was significantly more present in the low vitamin K2-treated groups in both the thoracic (P < 0.01) and abdominal aorta (P < 0.01) as compared with high vitamin K2-treated groups. Moreover, a high vitamin K diet and PBs led to reduced vascular oxidative stress. In an animal model of kidney failure with vitamin K deficiency, neither PB therapy nor vitamin K2 supplementation alone prevented VC. However, the combination of high vitamin K2 with PB treatment significantly attenuated VC.

Cisplatin is the first choice treatment in mediastinal germ cell tumors. However, concerns regarding increased toxicity of cisplatin hamper its administration in patients with impaired renal function. We describe a 42-year-old man with chronic kidney disease stage 4 who was diagnosed with a mediastinal germ cell tumor and metastases in lung and brain. Treatment with cisplatin-etoposide was considered essential for a chance of cure. In order to administer the full cisplatin dose, 4-hour hemodialysis sessions were performed after each cisplatin infusion. During treatment cycle 3, 4 and 5, total and unbound plasma platinum concentrations were measured. Trough concentrations and half-life were at the higher end of the range of those observed in patients with adequate renal function who received the same dose of cisplatin. Hemodialysis aided platinum clearance, although our patient was also able to clear some platinum by his own renal function. With this full dose treatment, our patient obtained a favorable tumor response, with a strong decrease of beta-human chorionic gonadotropin and tumor size. The side effects experienced by our patient were serious, although not worse than what could be expected with this type of treatment. His renal function remained stable during the treatment period.

IntroductionA growing number of dialysis patients is treated with home haemodialysis. Our current pre-analytical protocols require patients to centrifuge the blood sample and transfer the plasma into a new tube at home. This procedure is prone to errors and precludes accurate bicarbonate measurement, required for determining dialysate bicarbonate concentration and maintaining acid-base status. We therefore evaluated whether cooled overnight storage of gel separated plasma is an acceptable alternative.Materials and methodsVenous blood of 34 haemodialysis patients was collected in 2 lithium heparin blood collection tubes with gel separator (LH PSTTM II, REF 367374; Becton Dickinson, New Jersey, USA). One tube was analysed directly for measurement of bicarbonate, potassium, calcium, phosphate, glucose, urea, lactate, aspartate aminotransferase (AST), and lactate dehydrogenase (LD); whereas the other was centrifuged and stored unopened at 4 °C and analysed 24 h later. To measure analyte stability after 24 h of storage, the mean difference was calculated and compared to the total allowable error (TEa) which was used as acceptance limit.ResultsPotassium (Z = - 4.28, P < 0.001), phosphate (Z = - 3.26, P = 0.001), lactate (Z = - 5.11, P < 0.001) and AST (Z = - 2.71, P = 0.007) concentrations were higher, whereas glucose (Z = 4.00, P < 0.001) and LD (Z = 3.13, P = 0.002) showed a reduction. All mean differences were smaller than the TEa and thus not clinically relevant. Bicarbonate (Z = 0.69, P = 0.491), calcium (Z = - 0.23, P = 0.815) and urea (Z = 0.81, P =0.415) concentrations were stable.ConclusionsOur less complex, user-friendly pre-analytical procedure resulted in at least 24 h stability of analytes relevant for monitoring haemodialysis, including bicarbonate. This allows shipment and analysis the next day.