Efficacy of a Novel Injection Lipolysis to Induce Targeted Adipocyte Apoptosis: A Randomized, Phase IIa Study of CBL-514 Injection on Abdominal Subcutaneous Fat Reduction

Background: CBL-514 is a novel injectable drug that may be safe and efficacious for localized abdominal subcutaneous fat reduction. Objectives: The aim of this study was to assess the safety and efficacy of CBL-514 in reducing abdominal subcutaneous fat volume and thickness. Methods: This Phase IIa, open-label, random allocation study consisted of a 6-week treatment period and follow-up at 4 and 8 weeks following the last treatment. Participants were randomly allocated to receive 1.2 mg/cm2 (180 mg), 1.6 mg/cm2 (240 mg), or 2.0 mg/cm2 (300 mg) of CBL-514 with up to 4 treatments, each comprising 60 injections into the abdominal adipose layer. Changes in abdominal subcutaneous fat were assessed by ultrasound at follow-up visits. Treatment-emergent adverse events were recorded. Results: Higher doses of CBL-514 (unit dose, 2.0 and 1.6 mg/cm2) significantly improved the absolute and percentage reduction in abdominal fat volume (P < 0.00001) and thickness (P < 0.0001) compared with baseline. Although the COVID-19 pandemic halted some participant recruitment and follow-ups, analysis was unaffected, even after sample size limitations. Conclusions: CBL-514 injection at multiple doses up to 300 mg with a unit dose of 2.0 mg/cm2 is safe, well-tolerated, and reduced abdominal fat volume and thickness by inducing adipocyte apoptosis. Although other procedures exist to treat abdominal fat, they have limitations and may cause complications. At a dose of 2.0 mg/cm2, CBL-514 safely and significantly reduced abdominal fat volume by 24.96%, making it a promising new treatment for routine, nonsurgical abdominal fat reduction in dermatologic clinics. Level of Evidence: 4

Tetra­kis[μ-1,4-bis­(4,5-dihydro-1,3-oxazol-2-yl)benzene-κ2 N:N′]tetra­kis­(μ-methano­lato-κ2 O:O)bis­(μ-perchlorato-κ2 O:O′)tetra­copper(II) bis­(perchlorate)

The title tetra­nuclear CuII complex, [Cu4(C12H12N2O2)4(CH3O)4(ClO4)2](ClO4)2, is located around an inversion center. Each CuII atom is coordinated by two cis-O atoms from two bridging methano­late anions and two cis-N atoms from two bridging 1,4-bis­(4,5-dihydro-1,3-oxazol-2-yl)benzene (L) ligands in the basal plane, and is further coordinated by one O atom of the bridging perchlorate anion, forming a distorted square-pyramidal geometry. The Cu⋯Cu separations in the recta­ngular core are 2.9878 (11) and 6.974 (1) Å. In the asymmetric unit, there are two L ligands with a syn conformation. In one L ligand, the dihedral angles between the central benzene ring and the terminal 4,5-dihydro-1,3-oxazol-2-yl mean planes are 22.1 (4) and 33.1 (4)°, and in the other L ligand the corresponding dihedral angles are 29.3 (4) and 29.9 (4)°. The uncoordinated perchlorate anion is linked with the complex mol­ecules via weak C—H⋯O hydrogen bonds

Poly[(μ3-quinoline-6-carboxyl­ato-κ3 N:O:O′)silver(I)]

In the title coordination polymer, [Ag(C10H6NO2)]n, the AgI cation is coordinated by two O atoms and one N atom from three 6-quinoline­carboxyl­ate anions in a distorted T-shaped AgNO2 geometry, in which the O—Ag—O angle is 160.44 (9)°. The 6-quinoline­carboxyl­ate anion bridges three Ag+ cations, forming a nearly planar polymeric sheet parallel to (101). The distance between Ag+ cations bridged by the carboxyl group is 2.9200 (5) Å. In the crystal, π–π stacking is observed between parallel quinoline ring systems, the centroid–centroid distance being 3.7735 (16) Å

catena-Poly[[silver(I)-μ-1,2-bis­(4,4-dimethyl-4,5-dihydro-1,3-oxazol-2-yl)ethane-κ2 N:N′] perchlorate hemihydrate]

In the title coordination polymer, {[Ag(C12H20N2O2)]ClO4·0.5H2O}n, the AgI cation is coordinated by two N atoms from two 1,2-bis­(4,4-dimethyl-4,5-dihydro-1,3-oxazol-2-yl)ethane (L) ligands in a nearly linear geometry [N—Ag—N = 171.07 (8)°]. The L ligand bridges adjacent Ag+ cations, forming a polymeric chain running along the c axis. The lattice water mol­ecule is situated on a twofold rotation axis, and links to the perchlorate anion via an O—H⋯O hydrogen bond. The long Ag⋯O separation of 3.200 (4) Å indicates a weak inter­action between the perchlorate anion and the AgI cation. Weak C—H⋯O hydrogen bonding occurs between the chain and the lattice water mol­ecule and between the chain and perchlorate anions. Both five-membered rings of the L ligand display envelope conformations; in one five-membered ring, the flap C atom is disordered on opposite sides of the ring with occupancies of 0.65 and 0.35

China’s rising hydropower demand challenges water sector

Demand for hydropower is increasing, yet the water footprints (WFs) of reservoirs and hydropower, and their contributions to water scarcity, are poorly understood. Here, we calculate reservoir WFs (freshwater that evaporates from reservoirs) and hydropower WFs (the WF of hydroelectricity) in China based on data from 875 representative reservoirs (209 with power plants). In 2010, the reservoir WF totaled 27.9 × 109 m3 (Gm3), or 22% of China’s total water consumption. Ignoring the reservoir WF seriously underestimates human water appropriation. The reservoir WF associated with industrial, domestic and agricultural WFs caused water scarcity in 6 of the 10 major Chinese river basins from 2 to 12 months annually. The hydropower WF was 6.6 Gm3 yr−1 or 3.6 m3 of water to produce a GJ (109 J) of electricity. Hydropower is a water intensive energy carrier. As a response to global climate change, the Chinese government has promoted a further increase in hydropower energy by 70% by 2020 compared to 2012. This energy policy imposes pressure on available freshwater resources and increases water scarcity. The water-energy nexus requires strategic and coordinated implementations of hydropower development among geographical regions, as well as trade-off analysis between rising energy demand and water use sustainability

Long-term financing needs for HIV control in sub-Saharan Africa in 2015-2050: a modelling study

OBJECTIVES: To estimate the present value of current and future funding needed for HIV treatment and prevention in 9 sub-Saharan African (SSA) countries that account for 70% of HIV burden in Africa under different scenarios of intervention scale-up. To analyse the gaps between current expenditures and funding obligation, and discuss the policy implications of future financing needs. DESIGN: We used the Goals module from Spectrum, and applied the most up-to-date cost and coverage data to provide a range of estimates for future financing obligations. The four different scale-up scenarios vary by treatment initiation threshold and service coverage level. We compared the model projections to current domestic and international financial sources available in selected SSA countries. RESULTS: In the 9 SSA countries, the estimated resources required for HIV prevention and treatment in 2015–2050 range from US$98 billion to maintain current coverage levels for treatment and prevention with eligibility for treatment initiation at CD4 count of <500/mm(3) to US$261 billion if treatment were to be extended to all HIV-positive individuals and prevention scaled up. With the addition of new funding obligations for HIV—which arise implicitly through commitment to achieve higher than current treatment coverage levels—overall financial obligations (sum of debt levels and the present value of the stock of future HIV funding obligations) would rise substantially. CONCLUSIONS: Investing upfront in scale-up of HIV services to achieve high coverage levels will reduce HIV incidence, prevention and future treatment expenditures by realising long-term preventive effects of ART to reduce HIV transmission. Future obligations are too substantial for most SSA countries to be met from domestic sources alone. New sources of funding, in addition to domestic sources, include innovative financing. Debt sustainability for sustained HIV response is an urgent imperative for affected countries and donors