Neurological, Psychiatric, and Biochemical Aspects of Thiamine Deficiency in Children and Adults.

Thiamine (vitamin B1) is an essential nutrient that serves as a cofactor for a number of enzymes, mostly with mitochondrial localization. Some thiamine-dependent enzymes are involved in energy metabolism and biosynthesis of nucleic acids whereas others are part of the antioxidant machinery. The brain is highly vulnerable to thiamine deficiency due to its heavy reliance on mitochondrial ATP production. This is more evident during rapid growth (i.e., perinatal periods and children) in which thiamine deficiency is commonly associated with either malnutrition or genetic defects. Thiamine deficiency contributes to a number of conditions spanning from mild neurological and psychiatric symptoms (confusion, reduced memory, and sleep disturbances) to severe encephalopathy, ataxia, congestive heart failure, muscle atrophy, and even death. This review discusses the current knowledge on thiamine deficiency and associated morbidity of neurological and psychiatric disorders, with special emphasis on the pediatric population, as well as the putative beneficial effect of thiamine supplementation in autism spectrum disorder (ASD) and other neurological conditions

Genotypic classification of patients with Wolfram syndrome: insights into the natural history of the disease and correlation with phenotype

Purpose: Wolfram syndrome is a degenerative, recessive rare disease with an onset in childhood. It is caused by mutations in WFS1 or CISD2 genes. More than 200 different variations in WFS1 have been described in patients with Wolfram syndrome, which complicates the establishment of clear genotype-phenotype correlation. The purpose of this study was to elucidate the role of WFS1 mutations and update the natural history of the disease. Methods: This study analyzed clinical and genetic data of 412 patients with Wolfram syndrome published in the last 15 years. Results: (i) 15% of published patients do not fulfill the current ­inclusion criterion; (ii) genotypic prevalence differences may exist among countries; (iii) diabetes mellitus and optic atrophy might not be the first two clinical features in some patients; (iv) mutations are nonuniformly distributed in WFS1; (v) age at onset of diabetes mellitus, hearing defects, and diabetes insipidus may depend on the patient"s genotypic class; and (vi) disease progression rate might depend on genotypic class. Conclusion: New genotype-phenotype correlations were established, disease progression rate for the general population and for the genotypic classes has been calculated, and new diagnostic criteria have been proposed. The conclusions raised could be important for patient management and counseling as well as for the development of treatments for Wolfram syndrome

State of the Art Review: Emerging Therapies: The Use of Insulin Sensitizers in the Treatment of Adolescents with Polycystic Ovary Syndrome (PCOS)

PCOS, a heterogeneous disorder characterized by cystic ovarian morphology, androgen excess, and/or irregular periods, emerges during or shortly after puberty. Peri- and post-pubertal obesity, insulin resistance and consequent hyperinsulinemia are highly prevalent co-morbidities of PCOS and promote an ongoing state of excess androgen. Given the relationship of insulin to androgen excess, reduction of insulin secretion and/or improvement of its action at target tissues offer the possibility of improving the physical stigmata of androgen excess by correction of the reproductive dysfunction and preventing metabolic derangements from becoming entrenched. While lifestyle changes that concentrate on behavioral, dietary and exercise regimens should be considered as first line therapy for weight reduction and normalization of insulin levels in adolescents with PCOS, several therapeutic options are available and in wide use, including oral contraceptives, metformin, thiazolidenediones and spironolactone. Overwhelmingly, the data on the safety and efficacy of these medications derive from the adult PCOS literature. Despite the paucity of randomized control trials to adequately evaluate these modalities in adolescents, their use, particularly that of metformin, has gained popularity in the pediatric endocrine community. In this article, we present an overview of the use of insulin sensitizing medications in PCOS and review both the adult and (where available) adolescent literature, focusing specifically on the use of metformin in both mono- and combination therapy

Measurement of D0−D‾0D^0-\overline{D}^0 mixing and search for CPCP violation with D0→K+π−D^0\rightarrow K^+\pi^- decays

A measurement of the time-dependent ratio of the $D^0\rightarrow K^+\pi^-$ to $\overline{D}^0\rightarrow K^+\pi^-$ decay rates is reported. The analysis uses a sample of proton-proton collisions corresponding to an integrated luminosity of 6 fb$^-1$ recorded by the LHCb experiment from 2015 through 2018 at a center-of-mass energy of 13 TeV. The $D^0$ meson is required to originate from a $D^{*+}\rightarrow D^0\pi^+$ decay, such that its flavor at production is inferred from the charge of the accompanying pion. The measurement is performed simultaneously for the $K^+\pi^-$ and $K^-\pi^+$ final states, allowing both mixing and $CP$-violation parameters to be determined. The value of the ratio of the decay rates at production is determined to be $R_{K\pi} = (343.1 \pm 2.0) \times 10^{-5}$. The mixing parameters are measured to be $c_{K\pi} = (51.4 \pm 3.5) \times 10^{-4}$ and $c_{K\pi}^{\prime} = (13 \pm 4) \times 10^{-6}$, where $\sqrt{R_{K\pi}}c_{K\pi}$ is the linear coefficient of the expansion of the ratio as a function of decay time in units of the $D^0$ lifetime, and $c_{K\pi}^{\prime}$ is the quadratic coefficient, both averaged between the $K^+\pi^-$ and $K^-\pi^+$ final states. The precision is improved relative to the previous best measurement by approximately 60%. No evidence for $CP$ violation is found.Comment: All figures and tables, along with machine-readable versions and any supplementary material and additional information, are available at https://lhcbproject.web.cern.ch/Publications/LHCbProjectPublic/LHCb-PAPER-2024-008.htm

Search for resonance-enhanced CP and angular asymmetries in the Λc+→pμ+μ− decay at LHCb

The first measurement of the CP asymmetry of the decay rate (ACP) and the CP average (ΣAFB) and CP asymmetry (ΔAFB) of the forward-backward asymmetry in the muon system of Λþ c → pμþμ− decays is reported. The measurement is performed using a data sample of proton-proton collisions, recorded by the LHCb experiment from 2016 to 2018 at a center-of-mass energy of 13 TeV, which corresponds to an integrated luminosity of 5.4 fb−1. The asymmetries are measured in two regions of dimuon mass near the φ-meson mass peak. The dimuon-mass integrated results are ACP 1⁄4 ð−1.1 4.0 0.5Þ%, ΣAFB 1⁄4 ð3.9 4.0 0.6Þ%, ΔAFB 1⁄4 ð3.1 4.0 0.4Þ%, where the first uncertainty is statistical and the second systematic. The results are consistent with the conservation of CP symmetry and the Standard Model expectations

Search for the lepton-flavor violating decay Bs0 →φμ±τ

A search for the lepton-flavor violating decays Bs0→φμ±τ is presented, using a sample of proton-proton collisions at center-of-mass energies of 7, 8, and 13 TeV, collected with the LHCb detector and corresponding to a total integrated luminosity of 9 fb-1. The τ leptons are selected using decays with three charged pions. No significant excess is observed, and an upper limit on the branching fraction is determined to be B(Bs0→φμ±τ)<1.0×10-5 at 90% confidence level

Measurement of the branching fraction ratios R(D+)R(D^{+}) and R(D∗+)R(D^{*+}) using muonic τ\tau decays

The branching fraction ratios of $\overline{B}^0\to D^+\tau^-\overline{\nu}_{\tau}$ and $\overline{B}^0\to D^{*+}\tau^-\overline{\nu}_{\tau}$ decays are measured with respect to their muonic counterparts, using a data sample corresponding to an integrated luminosity of 2.0 fb$^{-1}$ collected by the LHCb experiment in proton-proton collisions at $\sqrt{s} = 13$ TeV. The reconstructed final states are formed by combining $D^+$ mesons with $\tau^-\to\mu^-\overline{\nu}_{\mu}\nu_{\tau}$ candidates, where the $D^+$ is reconstructed via the $D^+\to K^-\pi^+\pi^+$ decay. The results are \begin{align*} R(D^{+}) &= 0.249 \pm 0.043 \pm 0.047, R(D^{*+}) &= 0.402 \pm 0.081\pm 0.085, \end{align*} where the first uncertainties are statistical and the second systematic. The two measurements have a correlation coefficient of $-0.39$ and are compatible with the Standard Model.Comment: All figures and tables, along with machine-readable versions and any supplementary material and additional information, are available at https://lhcbproject.web.cern.ch/Publications/LHCbProjectPublic/LHCb-PAPER-2024-007.html (LHCb public pages

Measurement of the CKM angle γ in B± → DK*(892)± decays

Measurements of CP observables and the CKM angle γ are performed in B± → DK∗ (892)± decays, where D represents a superposition of D0 and D 0 states, using the LHCb dataset collected during Run 1 (2011–2012) and Run 2 (2015–2018). A study of this channel is presented with the D meson reconstructed in two-body fnal states K±π ∓, K+K− and π +π −; four-body fnal states K±π ∓π ±π ∓ and π +π −π +π −; and threebody fnal states K0 S π +π − and K0 SK+K−. This analysis includes the frst observation of the suppressed B± → [π ±K∓]DK∗± and B± → [π ±K∓π ±π ∓]DK∗± decays. The combined result gives γ = (63 ± 13)◦

Search for the rare decay of charmed baryon Λc+ into the pμ+μ- final state

A search for the nonresonant Λc+→pμ+μ- decay is performed using proton-proton collision data recorded at a center-of-mass energy of 13 TeV by the LHCb experiment, corresponding to an integrated luminosity of 5.4 fb-1. No evidence for the decay is found in the dimuon invariant-mass regions where the expected contributions of resonances is subdominant. The upper limit on the branching fraction of the Λc+→pμ+μ- decay is determined to be 2.9(3.2)×10-8 at 90%(95%) confidence level. The branching fractions in the dimuon invariant-mass regions dominated by the η, ρ and ω resonances are also determined

Search for D0 meson decays to π+π−e+e− and K+K−e+e− final states

A search for D0 meson decays to the πþπ−eþe− and KþK−eþe− final states is reported using a sample of proton-proton collisions collected by the LHCb experiment at a center-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 6 fb−1. The decay D0 → πþπ−eþe− is observed for the first time when requiring that the two electrons are consistent with coming from the decay of a φ or ρ0=ω meson. The corresponding branching fractions are measured relative to the D0 → K−π−1⁄2eþe−ρ0=ω decay, where the two electrons are consistent with coming from the decay of a ρ0 or ω meson. No evidence is found for the D0 → KþK−eþe− decay and world-best limits are set on its branching fraction. The results are compared to, and found to be consistent with, the branching fractions of the D0 → πþπ−μþμ− and D0 → KþK−μþμ− decays recently measured by LHCb and confirm lepton universality at the current precision