Longitudinal Phospho-tau217 Predicts Amyloid Positron Emission Tomography in Asymptomatic Alzheimer's Disease.

BACKGROUND: Blood-based AD biomarkers such as plasma P-tau217 are increasingly used in clinical trials as a screening tool. OBJECTIVES: To assess the utility of an electrochemiluminescence (ECL) immunoassay in predicting brain amyloid PET status in cognitively unimpaired individuals. SETTING: Plasma samples collected at baseline, week 12, and week 240 or endpoint originated from the Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) trial and the companion Longitudinal Evaluation of Amyloid Risk and Neurodegeneration (LEARN) study. PARTICIPANTS: Both A4 and LEARN enrolled eligible cognitively unimpaired persons 65 to 85 years. Individuals with elevated brain amyloid PET levels were eligible for the A4 Study, while those without elevated brain amyloid PET levels were eligible for the LEARN Study. INTERVENTION: Participants in the A4 Study received intravenous solanezumab (up to 1600 mg) or placebo every 4 weeks. The LEARN Study is an observational study without intervention. MEASUREMENTS: Plasma P-tau217 concentration levels from A4 Study participants were measured using an ECL immunoassay. Receiver Operating Characteristic (ROC) curve analysis was performed for each biomarker against amyloid positivity, defined by ≥22 CL and ≥ 33 CL. RESULTS: Receiver operating characteristic curve (ROC) analysis indicates high diagnostic value of P-tau217 in individuals with amyloid PET ≥ 20 (Area under the ROC (AUROC): 0.87) and ≥ 33 CL (AUROC: 0.89). Repeated testing with the placebo group taken 12 weeks apart (range: 68 to 143 days) and the LEARN participants taken between 1.4 and 1.75 years resulted in a strong positive correlation (Corr. 0.91 (0.90 to 0.92)). CONCLUSION: An ECL immunoassay testing plasma P-tau217 accurately predicts amyloid PET positivity in cognitively unimpaired individuals. Our future analyses aim to determine if use of this assay may reduce the screening burden of preclinical individuals into anti-amyloid clinical trials.

Maximizing the Utility of Alzheimer's Disease Trial Data: Sharing of Baseline A4 and LEARN Data.

BACKGROUND: The Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) and Longitudinal Evaluation of Amyloid Risk and Neurodegeneration (LEARN) studies were conducted between 2014 and 2023, with enrollment completed in 2017 and final study results reported in 2023. The study screening process involved the collection of initial clinical, cognitive, neuroimaging, and genetic measures to determine eligibility. Once randomized, enrolled participants were assessed every four weeks over a 4.5-year follow-up period during which longitudinal clinical, cognitive, and neuroimaging measures were collected. A large number of longitudinal fluid biospecimens were also collected and banked. Consistent with the NIH data sharing policy and the principles of Open Science, the A4/LEARN investigators aimed to share data as broadly and early as possible while still protecting participant privacy and confidentiality and the scientific integrity of the studies. OBJECTIVES: We describe the approach, methods, and platforms used to share the A4 and LEARN pre-randomization study data for secondary research use. Preliminary results measuring the impact of these efforts are also summarized. We conclude with a discussion of lessons learned and next steps. DESIGN: The materials shared included de-identified quantitative and image data, analysis software, instruments, and documentation. SETTING: The A4 and LEARN Studies were conducted at 67 clinical trial sites in the United States, Canada, Japan, and Australia. PARTICIPANTS: The A4 study screened (n=6763), enrolled, and randomized (n=1169) participants between the ages of 65 and 85 with a blinded follow-up period of 240 weeks followed by an open-label period of variable length. The LEARN study screened and enrolled individuals (n=538) who were ineligible for the A4 study based on nonelevated measures of amyloid accumulation using positron emission tomography imaging (amyloid PET). MEASUREMENTS: We provide descriptive measures of the data shared and summarize the frequency, characteristics, and status of all data access requests submitted to date. We evaluate the scientific impact of the data-sharing effort by conducting a literature search to identify related publications. RESULTS: The A4 and LEARN pre-randomization study data were released in December 2018. As of May 8, 2024, 1506 requests have been submitted by investigators and citizen scientists from more than 50 countries. We identified 49 peer-reviewed publications that acknowledge the A4/LEARN study. CONCLUSIONS: Our initial results provide evidence supporting the feasibility and scientific utility of broad and timely sharing of Alzheimer's disease trial data.

Acaricidal activity of Egyptian crude plant extracts against Haemaphysalis longicornis ticks.

Haemaphysalis longicornis is a common Ixodida tick species found in temperate areas of Asian countries. An anti-tick assay was conducted on adult female H. longicornis ticks. Plant extract solutions were prepared at concentrations of 50, 25, and 10 mg/mL. Tick survival and mortality were assessed by counting the number of dead and live ticks at 24 h, 48 h, 72 h, and 96 h posttreatment. Out of 11 plant extracts screened, Artemisia judaica extract exhibited the highest potency with 100% mortality (5/5) at 48 h when applied at high and moderate concentrations (50 and 25 mg/mL). Similar results were observed at 96 h for the 10 mg/mL group compared to the untreated ticks. Cleome droserifolia extract demonstrated partial activity with 60% (3/5) and 20% (1/5) mortality at 96 h posttreatment at concentrations of 50 and 25 mg/mL, respectively. Forsskaolea tenacissima extract showed a weak effect with 100% tick mortality (5/5) only at the highest treatment concentration after 96 h. To confirm the activity of A. judaica, trial 2 was conducted. A. judaica demonstrated potency within 48 h in high dose and 72 h in moderate dose, with 100% mortality (15/15) at 96 h posttreatment compared to untreated ticks. The median lethal time 50 (LT50) values were 30.37 h for the high and 55.08 h for the moderate doses. Liquid chromatography‒mass spectrometry was performed on the most potent candidate (A. judaica) to identify its phytochemical components. The results revealed the presence of 9 compounds identified through manual annotation and 74 compounds from the Global Natural Products Social library. These compounds included terpenoids, steroids, phenylpropanoids, flavonoid glycosides, flavonoids, and benzenoids. Camphor was identified as the major component via both approaches. These findings suggest the potential use of A. judaica extract in the future development of acaricidal therapeutics.

Extracts of wild Egyptian plants from the desert inhibit the growth of Toxoplasma gondii and Neospora caninum in vitro.

Wild medicinal plants have been traditionally used as antimicrobial agents. Here, we evaluated the in vitro activity of extracts from wild Egyptian desert plants against Toxoplasma gondii and Neospora caninum. From 12 plant extracts tested, the methanolic extracts from Artemisia judaica, Cleome droserifolia, Trichodesma africanum, and Vachellia tortilis demonstrated potent activity against the growth of T. gondii, with half-maximal inhibitory concentrations (IC50s) of 2.1, 12.5, 21.8, and 24.5 µg/ml, respectively. C. droserifolia, an ethanolic extract of P. undulata, T. africanum, A. judaica, and V. tortilis demonstrated potent efficacy against N. caninum, with mean IC50s of 1.0, 3.0, 3.1, 8.6, and 17.2 µg/ml, respectively. Our data suggest these extracts could provide an alternative treatment for T. gondii and N. caninum infections.

Wild Egyptian medicinal plants show in vitro and in vivo cytotoxicity and antimalarial activities.

BACKGROUND: Medicinal plants have been successfully used as an alternative source of drugs for the treatment of microbial diseases. Finding a novel treatment for malaria is still challenging, and various extracts from different wild desert plants have been reported to have multiple medicinal uses for human public health, this study evaluated the antimalarial efficacy of several Egyptian plant extracts. METHODS: We assessed the cytotoxic potential of 13 plant extracts and their abilities to inhibit the in vitro growth of Plasmodium falciparum (3D7), and to treat infection with non-lethal Plasmodium yoelii 17XNL in an in vivo malaria model in BALB/c mice. RESULTS: In vitro screening identified four promising candidates, Trichodesma africanum, Artemisia judaica, Cleome droserifolia, and Vachellia tortilis, with weak-to-moderate activity against P. falciparum erythrocytic blood stages with mean half-maximal inhibitory concentration 50 (IC50) of 11.7 µg/ml, 20.0 µg/ml, 32.1 µg/ml, and 40.0 µg/ml, respectively. Their selectivity index values were 35.2, 15.8, 11.5, and 13.8, respectively. Among these four candidates, T. africanum crude extract exhibited the highest parasite suppression in a murine malaria model against P. yoelii. CONCLUSION: Our study identified novel natural antimalarial agents of plant origin that have potential for development into therapeutics for treating malaria.

Electronic Cigarette or Vaping Product Use-Associated Lung Injury in a Previously Healthy Young Male.

Vaping (i.e., the use of electronic cigarettes) has been gaining popularity among people for the past few years, perhaps due to the misconception that its use is less harmful than traditional cigarettes. Although the long-term effects of these products are still unknown, it has been shown that they can be implicated in acute lung injury in healthy people. In 2019, an epidemic of severe acute lung injury was reported in the United States, and it was linked to vaping or electronic cigarette use and was referred to as e-cigarette or vaping product use-associated lung injury (EVALI). Here, we present the first case of EVALI in the state of Qatar.

Nilotinib-Induced Diabetes Mellitus in a Young Female with Chronic Myeloid Leukemia.

Chronic myeloid leukemia (CML) is one of the myeloproliferative neoplasms whose incidence peaks in older individuals and is characterized by the uncontrolled proliferation of cells in the myeloid cell line. It can present with symptoms related to leukocytosis or splenomegaly, and it can also be asymptomatic and found incidentally. Nilotinib is a second-generation tyrosine kinase inhibitor used in the treatment of the chronic phase of CML and was found to cause diabetes mellitus among other adverse effects. These adverse effects seem to occur after a few months to a few years of drug administration. Type-two diabetes is the most common type of diabetes; its hallmark being insulin resistance with resultant hyperglycemia. Most often, it has no symptoms and is usually found as an incidental finding or on screening. Here we present a 45-year old Chinese female, who was diagnosed with CML chronic phase after an incidental finding of leukocytosis; treated with nilotinib as upfront for CML, and developed diabetes mellitus after about one and a half years of treatment, which was treated with metformin.

Studies on some salicylaldehyde Schiff base derivatives and their complexes with Cr(III), Mn(II), Fe(III), Ni(II) and Cu(II).

The formation constants of some transition metal ions Cr(III), Mn(II), Fe(III), Ni(II) and Cu(II) binary complexes containing Schiff bases resulting from condensation of salicylaldehyde with aniline (I), 2-aminopyridine (II), 4-aminopyridine (III) and 2-aminopyrimidine (IV) were determined pH-metrically in ethanolic medium (80%, v/v). The formation constants were determined for all binary complexes. The important infrared (IR) spectral bands corresponding to the active groups in the four ligands and the solid complexes under investigation were studied. The solid complexes have been synthesized and studied by thermogravimetric analysis. The thermal dehydration and decomposition of these complexes were studied kinetically using the integral method applying the Coats-Redfern equation. It was found that the thermal decomposition of the complexes follow second order kinetics. The thermodynamic parameters of the decomposition are also reported. The electronic absorption spectra of the investigated ligands were carried out to determine the pK(a) values spectrophotometrically.

Potentiometric, spectrometric, thermal and conductimetric studies on some 3-phenyl-4-(arylazo)-5-pyrazolones and their complexes with divalent cobalt metal ion.

3-phenyl-4-arylazo-5-pyrazolones (I-IV) have been synthesized and characterized by elemental, infrared (IR), ultraviolet and visible spectra (UV-Vis), proton nuclear magnetic resonance (1H NMR) and Mass spectra. It has been proved that these compounds exhibit a keto-enol tautomerism in solution. The donor character of the substituent increases the enol form. The ionization constants of the investigated ligands have been determined potentiometrically and found to decrease in the order OCH(3)(IV)>CH(3)(III)>H(I)>Cl(II). The Co(II) complexes of the investigated 3-phenyl-4-arylazo-5-pyrazolones (I-IV) have been prepared and characterized by elemental and thermal analyses as well as by IR, UV-Vis, electronic transition, potentiometric, conductimetric and magnetic measurements. The data suggest octahedral geometry for Co(II) (1:1) complexes and tetrahedral for Co(II) (2:3) complexes.

Chronic atrophic rhinitis with fetor (ozena): a histopathologic tretise.

Biopsy material from 50 patients with a known clinical diagnosis of ozena was examined histopathologically. Certain features were invariably seen, including mucosal atrophy, squamous metaplasia, and chronic inflammatory cell infiltrate which suggests a humoral mediated immune process. Histopathologic features allow ozena to be distinguished from chronic non-specific hypertrophic rhinitis, which may have a cell-mediated immune basis underlying its pathogenesis.

Crystallographic study of rhinoliths.

Five nasal stones were extracted from five patients. The etiology and clinical picture have been discussed. The stones were analysed by a crystallographic method, using an X-ray diffraction technique. Their composition was identified as calcium phosphate.