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JPMA. the Journal of the Pakistan... Jun 2024To evaluate serum prolactin and macroprolactin levels in patients on long-term proton pump inhibitors therapy.
OBJECTIVES
To evaluate serum prolactin and macroprolactin levels in patients on long-term proton pump inhibitors therapy.
METHODS
The cross-sectional study was conducted from January 2018 to November 2019 after approval from the ethics review committee of the Commission on Science and Technology for Sustainable Development in the South University, Abbottabad, Pakistan. The study included patients from two gastroenterology outpatient clinics in the Khyber Pakhtunkhwa province using proton pump inhibitors for ≥3 months either alone or in combination with either histamine receptor antagonists or prokinetics. Blood samples were collected from each patient for hormonal screening. Data was analysed using SPSS 25.
RESULTS
Of the 166 patients, 101(60.8%) were females and 65(39.2%) were males. The overall mean age was 42.5±14.2 years, and the median serum prolactin level was 23.2ng/ml (interquartile range: 14.0-38.0ng/ml). There were 96(58%) patients with normoprolactinaemia and 70(42%) with hypreprolactinaemia. There were 19(11.4%) patients using combination therapy, while the rest were on proton pump inhibitors monotherapy. There was a significant increase in serum prolactin level with combination therapy compared to monotherapy (p=0.001). Patients having treatment duration 11-20 months (p=0.006) and >40 months (p=0.001) were at high risk of developing hyperprolactinaemia.
CONCLUSIONS
Long-term use of proton pump inhibitors could increase serum prolactin levels, and appropriate evaluation is essential for clinical management.
Topics: Humans; Proton Pump Inhibitors; Female; Cross-Sectional Studies; Male; Hyperprolactinemia; Prolactin; Adult; Middle Aged; Pakistan; Prevalence
PubMed: 38948973
DOI: 10.47391/JPMA.9541 -
BioRxiv : the Preprint Server For... Jun 2024To optimize a 100 msec pulse for producing CEST MRI contrast and evaluate in mice.
PURPOSE
To optimize a 100 msec pulse for producing CEST MRI contrast and evaluate in mice.
METHODS
A gradient ascent algorithm was employed to generate a family of 100 point, 100 msec pulses for use in CEST pulse trains ('PRECISE'). Gradient ascent optimizations were performed for exchange rates (k ) = 500 s , 1,500 s , 2,500 s , 3,500 s and 4,500 s and offsets (Δω) = 9.6, 7.8, 4.2 and 2.0 ppm. 7 PRECISE pulse shapes were tested on an 11.7 T scanner using a phantom containing three representative CEST agents with peak saturation B = 4 μT. The pulse producing the most contrast in phantoms was then evaluated for CEST MRI pH mapping of the kidneys in healthy mice after iopamidol administration.
RESULTS
The most promising pulse in terms of contrast performance across all three phantoms was the 9.6 ppm, 2500 s optimized pulse with ∼2.7 x improvement over Gaussian and ∼1.3x's over Fermi pulses. This pulse also displayed a large improvement in contrast over the Gaussian pulse after administration of iopamidol in live mice.
CONCLUSION
A new 100 msec pulse was developed based on gradient ascent optimizations which produced better contrast compared to standard Gaussian and Fermi pulses in phantoms. This shape also showed a substantial improvement for CEST MRI pH mapping in live mice over the Gaussian shape and appears promising for a wide range of CEST applications.
PubMed: 38948741
DOI: 10.1101/2024.06.19.599565 -
BioRxiv : the Preprint Server For... Jun 2024Gram-negative bacteria harness the proton motive force (PMF) within their inner membrane (IM) to uphold the integrity of their cell envelope, an indispensable aspect for...
UNLABELLED
Gram-negative bacteria harness the proton motive force (PMF) within their inner membrane (IM) to uphold the integrity of their cell envelope, an indispensable aspect for both division and survival. The IM TolQ-TolR complex is the essential part of the Tol-Pal system, serving as a conduit for PMF energy transfer to the outer membrane. Here we present cryo-EM reconstructions of TolQ in apo and TolR- bound forms at atomic resolution. The apo TolQ configuration manifests as a symmetric pentameric pore, featuring a trans-membrane funnel leading towards a cytoplasmic chamber. In contrast, the TolQ-TolR complex assumes a proton non-permeable stance, characterized by the TolQ pentamer's flexure to accommodate the TolR dimer, where two protomers undergo a translation-based relationship. Our structure-guided analysis and simulations support the rotor-stator mechanism of action, wherein the rotation of the TolQ pentamer harmonizes with the TolR protomers' interplay. These findings broaden our mechanistic comprehension of molecular stator units empowering critical functions within the Gram-negative bacterial cell envelope.
TEASER
Apo TolQ and TolQ-TolR structures depict structural rearrangements required for cell envelope organization in bacterial cell division.
PubMed: 38948712
DOI: 10.1101/2024.06.19.599759 -
Frontiers in Chemistry 2024Interfacial charge transfer reactions involving cations and electrons are fundamental to (photo/electro) catalysis, energy storage, and beyond. Lithium-coupled electron...
Interfacial charge transfer reactions involving cations and electrons are fundamental to (photo/electro) catalysis, energy storage, and beyond. Lithium-coupled electron transfer (LCET) at the electrode-electrolyte interfaces of lithium-ion batteries (LIBs) is a preeminent example to highlight the importance of charge transfer in modern-day society. The thermodynamics of LCET reactions define the minimal energy for charge/discharge of LIBs, and yet, these parameters are rarely available in the literature. Here, we demonstrate the successful incorporation of tungsten oxides (WO) within a chemically stable Zr-based metal-organic framework (MOF), MOF-808. Cyclic voltammograms (CVs) of the composite, WO@MOF-808, in Li-containing acetonitrile (MeCN)-based electrolytes showed an irreversible, cathodic Faradaic feature that shifted in a Nernstian fashion with respect to the Li concentration, i.e., ∼59 mV/log [(Li)]. The Nernstian dependence established 1:1 stoichiometry of Li and e. Using the standard redox potential of Li, the apparent free energy of lithiation of WO@MOF-808 (ΔG) was calculated to be -36 ± 1 kcal mol. ΔG is an parameter of WO@MOF-808, and thus by deriving the similar reaction free energies of other metal oxides, their direct comparisons can be achieved. Implications of the reported measurements will be further contrasted to proton-coupled electron transfer (PCET) reactions on metal oxides.
PubMed: 38947957
DOI: 10.3389/fchem.2024.1427536 -
ACS Omega Jun 2024In this study, S-deficient MoS was prepared using proton irradiation and then applied as sensing materials for the detection of NO gas. First, bulk MoS was treated by...
In this study, S-deficient MoS was prepared using proton irradiation and then applied as sensing materials for the detection of NO gas. First, bulk MoS was treated by ultrasonics to produce 2D nanosheets of MoS, which were subsequently bombarded by a flux of high-energy protons, resulting in the appearance of structural defects throughout MoS. The proton fluxes were adjusted to different densities of 1 × 10, 1 × 10, 1 × 10, and 1 × 10 ions/cm. The effects of proton irradiation on the defects, also referred to as atomic vacancies, were systematically investigated using Raman measurements to locate the E and A modes and X-ray photoelectron spectroscopy to determine the binding energy of Mo 3d and S 2p orbitals. It was revealed that the density of proton irradiation greatly affects the degree of S atom vacancies in irradiated MoS, while also enhancing the n-type semiconducting behaviors of MoS. The vacancy-rich MoS was then demonstrated to exhibit a higher response to NO gas compared to that of nonirradiated MoS, showing a 4-fold increase in response within a concentration range from 1 to 20 ppm. These results could pave the way for new approaches to fabricating sensing materials.
PubMed: 38947855
DOI: 10.1021/acsomega.4c00379 -
ACS Central Science Jun 2024Electron transport chains (ETCs) are ubiquitous in nearly all living systems. Replicating the complexity and control inherent in these multicomponent systems using...
Electron transport chains (ETCs) are ubiquitous in nearly all living systems. Replicating the complexity and control inherent in these multicomponent systems using ensembles of small molecules opens up promising avenues for molecular therapeutics, catalyst design, and the development of innovative energy conversion and storage systems. Here, we present a noncovalent, multistep artificial electron transport chains comprising cyclo[8]pyrrole (), a -aryl hexaphyrin(1.0.1.0.1.0) (naphthorosarin ), and the small molecules I and trifluoroacetic acid (TFA). Specifically, we show that 1) electron transfer occurs from to give I upon the addition of I, 2) proton-coupled electron transfer (PCET) from to give and upon the addition of TFA to a dichloromethane mixture of and , and 3) that further, stepwise treatment of and with I and TFA promotes electron transport from to give first I and then and . The present findings are substantiated through UV-vis-NIR, H NMR, electron paramagnetic resonance (EPR) spectroscopic analyses, cyclic voltammetry studies, and DFT calculations. Single-crystal structure analyses were used to characterize compounds in varying redox states.
PubMed: 38947209
DOI: 10.1021/acscentsci.4c00165 -
ACS Central Science Jun 2024
PubMed: 38947201
DOI: 10.1021/acscentsci.4c00459 -
Research Square Jun 2024Human manganese superoxide dismutase (MnSOD) plays a crucial role in controlling levels of reactive oxygen species (ROS) by converting superoxide (O ) to molecular...
Human manganese superoxide dismutase (MnSOD) plays a crucial role in controlling levels of reactive oxygen species (ROS) by converting superoxide (O ) to molecular oxygen (O ) and hydrogen peroxide (H O ) with proton-coupled electron transfers (PCETs). The reactivity of human MnSOD is determined by the state of a key catalytic residue, Tyr34, that becomes post-translationally inactivated by nitration in various diseases associated with mitochondrial dysfunction. We previously reported that Tyr34 has an unusual pK due to its proximity to the Mn metal and undergoes cyclic deprotonation and protonation events to promote the electron transfers of MnSOD. To shed light on the role of Tyr34 MnSOD catalysis, we performed neutron diffraction, X-ray spectroscopy, and quantum chemistry calculations of Tyr34Phe MnSOD in various enzymatic states. The data identifies the contributions of Tyr34 in MnSOD activity that support mitochondrial function and presents a thorough characterization of how a single tyrosine modulates PCET catalysis.
PubMed: 38946943
DOI: 10.21203/rs.3.rs-4494128/v1 -
World Journal of Gastroenterology Jun 2024In this editorial, we respond to a review article by Nabi , in which the authors discussed gastroesophageal reflux (GER) following peroral endoscopic myotomy (POEM).... (Review)
Review
In this editorial, we respond to a review article by Nabi , in which the authors discussed gastroesophageal reflux (GER) following peroral endoscopic myotomy (POEM). POEM is presently the primary therapeutic option for achalasia, which is both safe and effective. A few adverse effects were documented after POEM, including GER. The diagnostic criteria were not clear enough because approximately 60% of patients have a long acid exposure time, while only 10% experience reflux symptoms. Multiple predictors of high disease incidence have been identified, including old age, female sex, obesity, and a baseline lower esophageal sphincter pressure of less than 45 mmHg. Some technical steps during the procedure, such as a lengthy or full-thickness myotomy, may further enhance the risk. Proton pump inhibitors are currently the first line of treatment. Emerging voices are increasingly advocating for the routine combining of POEM with an endoscopic fundoplication method, such as peroral endoscopic fundoplication or transoral incisionless fundoplication. However, more research is necessary to determine the safety and effectiveness of these procedures in the long term for patients who have undergone them.
Topics: Humans; Gastroesophageal Reflux; Esophageal Achalasia; Proton Pump Inhibitors; Fundoplication; Myotomy; Treatment Outcome; Natural Orifice Endoscopic Surgery; Esophageal Sphincter, Lower; Risk Factors; Esophagoscopy
PubMed: 38946871
DOI: 10.3748/wjg.v30.i23.2947 -
Chemistry (Weinheim An Der Bergstrasse,... Jul 2024Developing a water-soluble, oxygen-tolerant, and acid-stable synthetic H2 production catalyst is vital for renewable energy infrastructure. To access such an effective...
Developing a water-soluble, oxygen-tolerant, and acid-stable synthetic H2 production catalyst is vital for renewable energy infrastructure. To access such an effective catalyst, we strategically incorporated enzyme-inspired, multicomponent outer coordination sphere elements around the cobaloxime (Cl-Co-X) core with suitable axial coordination (X). Our cobaloximes with axial imidazole or L-histidine coordination in photocatalytic HAT including the construction of anilines via a non-canonical cross-coupling approach is found superior compared to commonly used cobaloxime catalysts. The reversible Co(II)/Co(I) process is influenced by the axial N ligand's nature. Imidazole/ L-histidine with a higher pKa promptly produces H2 upon irradiation, leading to the improved reactivity compared to previously employed axial (di)chloride or pyridine analogue.
PubMed: 38946611
DOI: 10.1002/chem.202401785