Improving sarcopenia in older adults: a systematic review and meta-analysis of randomized controlled trials of whey protein supplementation with or without resistance training.

OBJECTIVES: The aim of the study was to comprehensively analyze the effects of whey protein (WP)-enriched supplement intake with or without resistance training (RT) in older patients, either from the community or hospital, who were diagnosed with sarcopenia according to the EWGSOP or AWGS criteria. METHODS: This meta-analysis study was registered in PROSPERO (CRD42023407885). We searched the PubMed, Embase, Web of Science, and Cochrane Library databases for RCTs up to June 1, 2023. Standardized mean differences (SMD) with 95% confidence intervals (CI) were used to estimate the pooled results. RESULTS: Ten RCT studies, including 1154 participants, were included and analyzed. The primary outcomes were the changes in muscle mass, strength, and physical performance. In WP group versus (vs.) Isocaloric placebo (PLA)/Routine consultation (RC) group, WP significantly increased the appendicular skeletal muscle mass index (SMD: 0.47, 95%CI: 0.23, 0.71), appendicular skeletal muscle mass (SMD: 0.28, 95%CI: 0.11, 0.45) and gait speed (SMD: 1.13, 95%CI: 0.82, 1.44) in older patients with sarcopenia. In WP with RT group vs. PLA/ RC group, there was significant increase in handgrip strength (SMD: 0.67, 95%CI: 0.29, 1.04). In addition, in the secondary outcomes, WP significantly reduced interleukin-6, significantly increased insulin-like growth factor-1 and albumin, promoted participants' intake of total energy and protein, enhanced activities of daily living scores in patients, and had no significant effect on BMI, weight, or fat mass. CONCLUSION: This review confirms that WP can improve various aspects of older adult with sarcopenia, thereby enhancing their overall physical condition. More studies should be conducted to validate this result and further explore the effects of WP and RT in patients with sarcopenia.

A state-of-the-art review of functional magnetic resonance imaging technique integrated with advanced statistical modeling and machine learning for primary headache diagnosis.

Primary headache is a very common and burdensome functional headache worldwide, which can be classified as migraine, tension-type headache (TTH), trigeminal autonomic cephalalgia (TAC), and other primary headaches. Managing and treating these different categories require distinct approaches, and accurate diagnosis is crucial. Functional magnetic resonance imaging (fMRI) has become a research hotspot to explore primary headache. By examining the interrelationships between activated brain regions and improving temporal and spatial resolution, fMRI can distinguish between primary headaches and their subtypes. Currently the most commonly used is the cortical brain mapping technique, which is based on blood oxygen level-dependent functional magnetic resonance imaging (BOLD-fMRI). This review sheds light on the state-of-the-art advancements in data analysis based on fMRI technology for primary headaches along with their subtypes. It encompasses not only the conventional analysis methodologies employed to unravel pathophysiological mechanisms, but also deep-learning approaches that integrate these techniques with advanced statistical modeling and machine learning. The aim is to highlight cutting-edge fMRI technologies and provide new insights into the diagnosis of primary headaches.

Untargeted lipidomic analysis and network pharmacology for parthenolide treated papillary thyroid carcinoma cells.

BACKGROUND: With fast rising incidence, papillary thyroid carcinoma (PTC) is the most common head and neck cancer. Parthenolide, isolated from traditional Chinese medicine, inhibits various cancer cells, including PTC cells. The aim was to investigate the lipid profile and lipid changes of PTC cells when treated with parthenolide. METHODS: Comprehensive lipidomic analysis of parthenolide treated PTC cells was conducted using a UHPLC/Q-TOF-MS platform, and the changed lipid profile and specific altered lipid species were explored. Network pharmacology and molecular docking were performed to show the associations among parthenolide, changed lipid species, and potential target genes. RESULTS: With high stability and reproducibility, a total of 34 lipid classes and 1736 lipid species were identified. Lipid class analysis indicated that parthenolide treated PTC cells contained higher levels of fatty acid (FA), cholesterol ester (ChE), simple glc series 3 (CerG3) and lysophosphatidylglycerol (LPG), lower levels of zymosterol (ZyE) and Monogalactosyldiacylglycerol (MGDG) than controlled ones, but with no significant differences. Several specific lipid species were changed significantly in PTC cells treated by parthenolide, including the increasing of phosphatidylcholine (PC) (12:0e/16:0), PC (18:0/20:4), CerG3 (d18:1/24:1), lysophosphatidylethanolamine (LPE) (18:0), phosphatidylinositol (PI) (19:0/20:4), lysophosphatidylcholine (LPC) (28:0), ChE (22:6), and the decreasing of phosphatidylethanolamine (PE) (16:1/17:0), PC (34:1) and PC (16:0p/18:0). Four key targets (PLA2G4A, LCAT, LRAT, and PLA2G2A) were discovered when combining network pharmacology and lipidomics. Among them, PLA2G2A and PLA2G4A were able to bind with parthenolide confirmed by molecular docking. CONCLUSIONS: The changed lipid profile and several significantly altered lipid species of parthenolide treated PTC cells were observed. These altered lipid species, such as PC (34:1), and PC (16:0p/18:0), may be involved in the antitumor mechanisms of parthenolide. PLA2G2A and PLA2G4A may play key roles when parthenolide treated PTC cells.

Prognostic and clinicopathologic significance of PLIN2 in cancers: A systematic review with meta-analysis.

The relationship between PLIN2 expression and prognosis, and clinicopathological significance of various cancers has been extensively studied, but the results are not completely consistent. This review followed the guidelines for systematic reviews of prognostic factors studies and was reported under the Preferred Reporting Program for Systematic Reviews and Meta-Analysis (PRISMA). We searched PubMed, Embase, Cochrane Library, Web of Science, and Google Academia for relevant articles up to September 2, 2022, and calculated the pooled hazard ratios (HR) with 95% confidence intervals (CI) to determine the association between PLIN2 expression and the prognosis of various cancers. The meta-analysis ultimately included 17 studies. The quality of all included cohort studies was evaluated using the Quality in Prognosis Studies (QUIPS) tool, and an adaptation of Grading of Recommendations Assessment, Development and Evaluation (GRADE) method was used to assess the certainty of the results. High expression of PLIN2 was associated with poorer overall survival (HR = 1.65; 95% CI = 1.14, 2.38; P = 0.008), metastasis-free survival (HR = 1.48; 95% CI = 1.12, 1.94; P = 0.005), progression-free survival (HR = 2.11; 95% CI = 1.55, 2.87; P < 0.0005) and recurrence-free survival/relapse-free survival (HR = 2.21; 95% CI = 1.64, 2.98; P < 0.0005) in cancers. The clinicopathological parameters of digestive system malignancies suggested that high expression of PLIN2 was notably associated with distant metastasis ( + ) (odds ratio (OR) = 3.37; 95% CI = 1.31, 8.67; P = 0.012), lymph node metastasis ( + ) (OR = 1.61; 95% CI = 1.01, 2.54; P = 0.004), and tumor stage (III-IV) (OR = 1.96; 95% CI = 1.24, 3.09; P = 0.006). In summary, overexpression of PLIN2 is significantly associated with a poor prognosis in various human cancers, especially in respiratory and digestive malignancies. Thus, PLIN2 expression may be a potential prognostic biomarker in cancer patients.

A First for Human Vaccinology: GMP Compliant Radiation Attenuation of Plasmodium falciparum Sporozoites for Production of a Vaccine Against Malaria.

Ionizing radiation (UV, X-ray and É£) administered at an appropriate dose to pathogenic organisms can prevent replication while preserving metabolic activity. We have established the GMP process for attenuation by ionizing radiation of the Plasmodium falciparum (Pf) sporozoites (SPZ) in Sanaria® PfSPZ Vaccine, a protective vaccine against malaria. Mosquitoes raised and infected aseptically with Pf were transferred into infected mosquito transport containers (IMTC) and É£-irradiated using a 60Co source. PfSPZ were then extracted, purified, vialed, and cryopreserved. To establish the appropriate radiation conditions, the irradiation field inside the IMTCs was mapped using radiochromic film and alanine transfer dosimeters. Dosimeters were irradiated for times calculated to provide 120-170 Gy at the minimum dose location inside the IMTC and regression analysis was used to determine the time required to achieve a lower 95% confidence interval for 150 Gy. A formula incorporating the half-life of 60Co was then used to construct tables of irradiation times for each calendar day. From the mapping studies, formulae were derived to estimate the minimum and maximum doses of irradiation received inside the IMTC from a reference dosimeter mounted on the outside wall. For PfSPZ Vaccine manufacture a dose of 150 Gy was targeted for each irradiation event, a dose known to completely attenuate PfSPZ. The reference dosimeters were processed by the National Institute of Standards and Technology. There have been 587 irradiation events to produce PfSPZ Vaccine during 13 years which generated multiple lots released for pre-clinical studies and clinical trials. The estimated doses at the minimum dose location (mean 154.3 ± 1.77 Gy; range 150.0-159.3 Gy), and maximum dose location (mean 166.3 ± 3.65 Gy, range 155.7 to 175.3 Gy), in IMTCs were normally distributed. Overall dose uniformity was 1.078 ± 0.012. There was no siginifcant change in measured dose over 13 years. As of January 2022, 21 clinical trials of PfSPZ Vaccine have been conducted, with 1,740 volunteers aged 5 months to 61 years receiving 5,648 doses of PfSPZ Vaccine totalling >5.3 billion PfSPZ administered. There have been no breakthrough infections, confirming the consistency and robustness of the radiation attenuation process.

Optimizing Intradermal Administration of Cryopreserved Plasmodium falciparum Sporozoites in Controlled Human Malaria Infection.

Controlled human malaria infection (CHMI) is a powerful tool to evaluate malaria vaccine and prophylactic drug efficacy. Until recently CHMI was only carried out by the bite of infected mosquitoes. A parenteral method of CHMI would standardize Plasmodium falciparum sporozoite (PfSPZ) administration, eliminate the need for expensive challenge facility infrastructure, and allow for use of many P. falciparum strains. Recently, intradermal (ID) injection of aseptic, purified, cryopreserved PfSPZ was shown to induce P. falciparum malaria; however, 100% infection rates were not achieved by ID injection. To optimize ID PfSPZ dosing so as to achieve 100% infection, 30 adults aged 18-45 years were randomized to one of six groups composed of five volunteers each. The parameters of dose (1 × 10(4) versus 5 × 10(4) PfSPZ total dose per volunteer), number of injections (two versus eight), and aliquot volume per ID injection (10 µL versus 50 µL) were studied. Three groups attained 100% infection: 1 × 10(4) PfSPZ in 50 µL/2 doses, 1 × 10(4) PfSPZ in 10 µL/2 doses, and 5 × 10(4) PfSPZ in 10 µL/8 doses. The group that received 5 × 10(4) PfSPZ total dose in eight 10 µL injections had a 100% infection rate and the shortest prepatent period (mean of 12.7 days), approaching the prepatent period for the current CHMI standard of five infected mosquitoes.