ABSTRACTBackground: This analysis aimed to evaluate the effectiveness of eliciting sexual partners from HIV-positive clients using the elicitation box model (where an HIV-positive index can report sexual contacts on paper and insert in a box for a health care provider to contact at a later time) compared to the conventional model (in which a health care provider elicits sexual contacts directly from clients) in Akwa Ibom, Southern Nigeria.Methods: Between March 2021 and April 2022, data were collected from index testing registers at 4 health facilities with a high volume of HIV clients currently on treatment in 4 local government areas in Akwa Ibom State. Primary outcome analyzed was the elicitation ratio (number of partners elicited per HIV-index offered index testing services). Secondary outcomes were the index testing acceptance (index HIV-positive clients accepted index testing service), testing coverage (partners tested for HIV from a list of partners elicited from HIV-index accepted index testing services), testing yield (index partners identified HIV positive from index partners HIV-tested), and linkage rate (index partners identified HIV positive and linked to antiretroviral therapy).Results: Of the total 2,705 index clients offered index testing services, 91.9% accepted, with 2,043 and 439 indexes opting for conventional elicitation and elicitation box models, respectively. A total of 3,796 sexual contacts were elicited: 2,546 using the conventional model (elicitation ratio=1:1) and 1,250 using the elicitation box model (elicitation ratio=1:3). Testing coverage was significantly higher in the conventional compared to the elicitation box model (P<.001). However, there was no significant difference in the testing yield (P=.81) and linkage rate using the conventional compared to elicitation box models (P=.13).Conclusion: The implementation of the elicitation box model resulted in an increase in partner elicitation compared to the conventional model. Increasing the testing coverage by implementing the elicitation box model should be considered.

The development of transforming growth factor βreceptor inhibitors (TGFβRi) as new medicines has been affected by cardiac valvulopathy and arteriopathy toxicity findings in nonclinical toxicology studies. PF-06952229 (MDV6058) selected using rational drug design is a potent and selective TGFβRI inhibitor with a relatively clean off-target selectivity profile and good pharmacokinetic properties across species. PF-06952229 inhibited clinically translatable phospho-SMAD2 biomarker (≥60%) in human and cynomolgus monkey peripheral blood mononuclear cells, as well as in mouse and rat splenocytes. Using an optimized, intermittent dosing schedule (7-day on/7-day off/cycle; 5 cycles), PF-06952229 demonstrated efficacy in a 63-day syngeneic MC38 colon carcinoma mouse model. In the pivotal repeat-dose toxicity studies (rat and cynomolgus monkey), PF-06952229 on an intermittent dosing schedule (5-day on/5-day off cycle; 5 cycles, 28 doses) showed no cardiac-related adverse findings. However, new toxicity findings related to PF-06952229 included reversible hepatocellular (hepatocyte necrosis with corresponding clinically monitorable transaminase increases) and lung (hemorrhage with mixed cell inflammation) findings at ≥ targeted projected clinical efficacious exposures. Furthermore, partially reversible cartilage hypertrophy (trachea and femur in rat; femur in monkey) and partially to fully reversible, clinically monitorable decreases in serum phosphorus and urinary phosphate at ≥ projected clinically efficacious exposures were observed. Given the integral role of TGFβ in endochondral bone formation, cartilage findings in toxicity studies have been observed with other TGFβRi classes of compounds. The favorable cumulative profile of PF-06952229 in biochemical, pharmacodynamic, pharmacokinetic, and nonclinical studies allowed for its evaluation in cancer patients using the intermittent dosing schedule (7-day on/7-day off) and careful protocol-defined monitoring.

Chronic hypertension leads to injury and fibrosis in major organs. Fibroblast activation protein (FAP) is one of key molecules in tissue fibrosis, and ⁶⁸Ga-labeled FAP inhibitor-46 (FAPI46) PET is a recently developed method for evaluating FAP. The aim of this study was to evaluate FAP expression and fibrosis in a hypertension model and to test the feasibility of ⁶⁸Ga-FAPI46 PET in hypertension. Methods: Hypertension was induced in mice by angiotensin II infusion for 4 wk. ⁶⁸Ga-FAPI46 biodistribution studies and PET scanning were conducted at 1, 2, and 4 wk after hypertension modeling, and uptake in the major organs was measured. The FAP expression and fibrosis formation of the heart and kidney tissues were analyzed and compared with ⁶⁸Ga-FAPI46 uptake. Subgroups of the hypertension model underwent angiotensin receptor blocker administration and high-dose FAPI46 blocking, for comparison. As a preliminary human study, ⁶⁸Ga-FAPI46 PET images of lung cancer patients were analyzed and compared between hypertension and control groups. Results: Uptake of ⁶⁸Ga-FAPI46 in the heart and kidneys was significantly higher in the hypertension group than in the sham group as early as week 1 and decreased after week 2. The uptake was specifically blocked in the high-dose blocking study. Immunohistochemistry also revealed FAP expression in both heart and kidney tissues. However, overt fibrosis was observed in the heart, whereas it was absent from the kidneys. The angiotensin receptor blocker–treated group showed lower uptake in the heart and kidneys than did the hypertension group. In the pilot human study, renal uptake of ⁶⁸Ga-FAPI46 significantly differed between the hypertension and control groups. Conclusion: In hypertension, FAP expression is increased in the heart and kidneys from the early phases and decreases over time. FAP expression appears to represent fibrosis activity preceding or underlying fibrotic tissue formation. ⁶⁸Ga-FAPI46 PET has potential as an effective imaging method for evaluating FAP expression in progressive fibrosis by hypertension.

²²⁶Ac (t_1/2 = 29.37 h) has been proposed as a theranostic radioisotope leveraging both its diagnostic -emissions and therapeutic α-emissions. ²²⁶Ac emits 158 and 230 keV -photons ideal for quantitative SPECT imaging and acts as an in vivo generator of 4 high-energy α-particles. Because of these nuclear decay properties, ²²⁶Ac has potential to act as a standalone theranostic isotope. In this proof-of-concept study, we evaluated a preclinical ²²⁶Ac-radiopharmaceutical for its theranostic efficacy and present the first ²²⁶Ac-targeted α-therapy study. Methods: ²²⁶Ac was produced at TRIUMF and labeled with the chelator-peptide bioconjugate crown-TATE. [²²⁶Ac]Ac-crown-TATE was selected to target neuroendocrine tumors in male NRG mice bearing AR42J tumor xenografts for SPECT imaging, biodistribution, and therapy studies. A preclinical SPECT/CT scanner acquired quantitative images reconstructed from both the 158 and the 230 keV emissions. Mice in the biodistribution study were euthanized at 1, 3, 5, 24, and 48 h after injection, and internal radiation dosimetry was derived for the tumor and organs of interest to establish appropriate therapeutic activity levels. Mice in the therapy study were administered 125, 250, or 375 kBq treatments and were monitored for tumor size and body condition. Results: We present quantitative SPECT images of the in vivo biodistribution of [²²⁶Ac]Ac-crown-TATE, which showed agreement with ex vivo measurements. Biodistribution studies demonstrated high uptake (>30%IA/g at 5 h after injection) and retention in the tumor, with an estimated mean absorbed dose coefficient of 222 mGy/kBq. [²²⁶Ac]Ac-crown-TATE treatments significantly extended the median survival from 7 d in the control groups to 16, 24, and 27 d in the 125, 250, and 375 kBq treatment groups, respectively. Survival was prolonged by slowing tumor growth, and no weight loss or toxicities were observed. Conclusion: This study highlights the theranostic potential of ²²⁶Ac as a standalone therapeutic isotope in addition to its demonstrated diagnostic capabilities to assess dosimetry in matched ²²⁵Ac-radiopharmaceuticals. Future studies will investigate maximum dose and toxicity to further explore the therapeutic potential of ²²⁶Ac-radiopharmaceuticals.

BACKGROUND AND PURPOSE:

Gadolinium-based contrast agents are widely used for meningioma imaging; however, concerns exist regarding their side effects, cost, and environmental impact. At the standard gadolinium dose, most meningiomas show avid contrast enhancement, suggesting that administering a smaller dose may be feasible. The purpose of this study was to evaluate the impact of a lower gadolinium dose on the differentiation between meningiomas and adjacent intracranial tissues.

The aim of this work is to test whether the use of a transparent capsule affects the residual capsule weight after inhalation as a surrogate of the inhaled delivered dose for patients with non-reversible chronic airway disease. Researchers conducted an observational cross-sectional study with patients using a single-dose dry powder inhaler. The weight of the capsule was measured with a precision microbalance before and after inhalation. Ninety-one patients were included, of whom 63 (69.2%) used a transparent capsule. Inhalation with a transparent capsule achieved a weight decrease of 30.1% vs 8.6% for devices with an opaque capsule (P <0.001). These data reinforce the need to provide patients with mechanisms that verify the correct inhalation technique.

There must be hundreds of typewriters in the hall, their collective clacks a tidal wave of soulless automation, rising up to greet agent Kiran Estevez as she enters, pistol and flashlight in hands. Exploring rooms to the side, Alan Wake 2: The Lake House’s star finds whiteboards and documents revealing the typewriter’s purpose: to mimic Wake’s writing. Pages are graded along criteria such as ‘style’, ‘tone’, and ‘content’, then “fed into the algorithm” as references until “near-identical stories” to Wake’s can be produced.

“If Jules could simply cut the painter open and pull the painting out of him, he would,” reads one of the real Alan’s typewritten pages. That’s Jules Marmont, the obsessive head of the titular FBC centre. The Marmonts - Jules and his wife Diana - are running experiments to forcibly and synthetically create works of art, aiming to mimic creative passion convincingly enough for the paranatural entity inside Cauldron Lake to respond, as it has in the past.

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September 29 is observed as World Heart Day

Read our full review of eharmony or our comparability of eharmony vs. EliteSingles. Online courting is type of the most effective factor that is ever occurred to introverts. Simply join, add your time and place of origin to generate your chart, and state the type of relationship you’re looking for. If you’re in search of […]

National Bureau of Economic Research

IEEE / Institute of Electrical and Electronics Engineers Incorporated