Mpox outbreak in Rio de Janeiro, Brazil: A translational approach.

Mpox is a zoonotic disease historically reported in Africa. Since 2003, limited outbreaks have occurred outside Africa. In 2022, the global spread of cases with sustained interhuman transmission and unusual disease features raised public health concerns. We explore the mpox outbreak in Rio de Janeiro (RJ) state, Brazil, in an observational study of mpox-suspected cases from June to December 2022. Data collection relied on a public healthcare notification form. Diagnosis was determined by MPXV-PCR. In 46 confirmed cases, anti-OPXV IgG was determined by ELISA, and seven MPXV genomes were sequenced. A total of 3095 cases were included, 816 (26.3%) with positive MPXV-PCR results. Most positive cases were men in their 30 s and MSM. A total of 285 (34.9%) MPXV-PCR+ patients live with HIV. Eight were coinfected with varicella-zoster virus. Anogenital lesions and adenomegaly were associated with the diagnosis of mpox. Females and individuals under 18 represented 9.4% and 5.4% of all confirmed cases, respectively, showing higher PCR cycle threshold (Ct) values and fewer anogenital lesions compared to adult men. Anti-OPXV IgG was detected in 29/46 (63.0%) patients. All analyzed sequences belonged to clade IIb. In RJ state, mpox presented a diverse clinical picture, represented mainly by mild cases with low complication rates and prominent genital involvement. The incidence in females and children was higher than usually reported. The observation of a bimodal distribution of Ct values, with few positive results, may suggest the need to review the diagnostic criteria in these groups.

An approach based on genetic algorithms and machine learning coupled for studying alloy and molecular clusters by optimizing quantum energy surfaces.

A new genetic algorithm has been proposed focusing on direct ab initio potential energy surface (PES) global minima search. Besides the commonly used operators, this new approach uses an operator to: improve the initial cluster generation, classify and compare all generated clusters, and use machine learning to model the quantum PES used in parallel optimization. Part of the validation process for this methodology was done with C u n A u m ( n + m ≤ X for X = 14 , 19 , 38 , 55 ) and A u n A g n ( n = 10 , 20 , 30 , 40 , 50 , 60 , 70 , and 75). The results are in fair agreement with the literature and led to a new global minimum for C u 12 A u 7 . A search has been done for the lowest energies of L i n nanoclusters with 2-8 atoms using the DFT approach and for L i 3 , L i 4 , L i 2 H , L i 3 H using DLPNO-CCSD(T) approach. NQGA successfully performed the MP2 optimizations for ( H 2 O ) 11 cluster. In all cases, the proposed genetic algorithm located the previously reported global minima with very efficient performance. The new proposed methodology makes it possible to optimize cluster geometries directly using high-level ab initio methods relinquishing any bias introduced by a classical approach. Our results show that this proposed method has great potential applications due to its flexibility and efficiency in identifying global minima in the tested atomic systems.

Role of transverse diameter of the rectum in lower urinary tract symptoms and functional constipation in children and adolescents.

AIM: Although a correlation has been reported between enlarged rectal diameter and functional constipation (FC), the relevance of measuring the transverse diameter of the rectum for diagnosing FC remains unclear, even in patients with lower urinary tract symptoms (LUTS). This study aimed to measure rectal diameter in children/adolescents diagnosed with LUTS, with and without FC. METHODS: This cross-sectional study included 4-17 years old children/adolescents attending a multidisciplinary outpatient clinic for urinary disorders between June 2016 and November 2018. All participants had LUTS, with or without FC. Those incorrectly completing the study questionnaires or with neurological and/or anatomical abnormalities of the genitourinary and/or gastrointestinal tract were excluded. Urinary symptoms were evaluated using the dysfunctional voiding symptom score and FC was assessed using the Rome IV criteria. Transabdominal ultrasonography was used to evaluate the bladder and measure rectal diameter. A transverse diameter ≥3 cm defined an enlarged rectum. Bladder capacity (i.e. the bladder volume immediately before voiding), post-void residual urine, bladder wall thickness and first volume voided after ultrasonography were measured. RESULTS: Mean age was 8.9 ± 3.2 years and 55.1% were female. Of 107 patients included, constipation was diagnosed in 72 (67.3%), and lower urinary tract dysfunction in 90 (84.1%). In 72 participants (67.3%), lower urinary tract dysfunction was associated with FC, constituting bladder and bowel dysfunction. Rectal diameter was increased in 51 patients (47.7%). There was no association between rectal diameter ≥ 3 cm and urinary urgency, enuresis, increased daytime urinary frequency, nocturia, daytime incontinence, constipation, severe LUTS or bladder and bowel dysfunction (P > 0.05 in all cases). However, increased rectal diameter was associated with at least one episode of faecal incontinence per week in constipated patients (P = 0.02). There was no correlation between rectal diameter and dysfunctional voiding symptom score (rs = 0.00), bladder capacity (rs = 0.01), post-void residual urine (rs = 0.05), bladder wall thickness (rs = 0.00) or first volume voided after ultrasonography (rs = 0.06); P > 0.05 in all cases. CONCLUSION: There was no association between the current cut-off point characterising the rectum as distended and the severity of urinary symptoms, even when FC was present. However, the complaint of faecal incontinence associated with increased rectal diameter may suggest functional constipation. The cross-sectional design, however, constitutes a limitation. Further studies may be able to determine the ideal diagnostic cut-off point for bowel and urinary dysfunction. Rectal diameter was not associated with the intensity of LUTS, with or without FC. However, the complaint of faecal incontinence associated with increased rectal diameter may suggest functional constipation.

Application of a quantum genetic algorithm and QTAIM analysis in the study of structural and electronic properties of neutral bimetallic clusters NaxLiy (4 ≤ x + y ≤ 10).

Alloy clusters of NaxLiy (4 ≤ x + y ≤ 10) are studied by exploring the potential energy surface in the ab initio MP2 level with the support of a quantum genetic algorithm (QGA). In some cases, the structures have been also refined with DFT and coupled-cluster methods. The general trends of sodium-lithium structures are in line with previous studies. The ionization potentials and polarizabilities to all structures were calculated with MP2 method and the average error between these two properties compared with experimental data was 6% and 13%, respectively. The topological analysis based on quantum theory of atoms in molecules (QTAIM) showed that by increasing the cluster size of the diatomic system there was a decrease of atomic interaction energies. The degree of degeneracy from D3BIA aromaticity index and the analysis of the atomic charges showed the influence (by charge transfer) of the chemical element in lower quantity in the cluster with respect to the other atoms. Our achievements of comparing our theoretical results with available experimental data have demonstrated that our approach can also predict satisfactorily quantum atomic and alloy clusters properties, at least, for low nuclearities.

Determination of Anticancer Zn(II)-Rutin Complex Structures in Solution through Density Functional Theory Calculations of 1H NMR and UV-VIS Spectra.

Coordination compounds formed by flavonoid ligands are recognized as promising candidates as novel drugs with enhanced antioxidant and anticancer activity. Zn(II)-Rutin complexes have been described in the literature and distinct coordination modes proposed based on 1H NMR/MS and IR/UV-VIS experimental spectroscopic data: 1:1/1:2 (Zn(II) binding to A-C rings) and 2:1 (Zn(II) binding to A-C-B rings) stoichiometry. Aiming to clarify these experimental findings and provide some physical insights into the process of complex formation in solution, we carried out density functional theory calculations of NMR and UV-VIS spectra for 25 plausible Zn(II)-Rutin molecular structures including solvent effect using the polarizable continuum model approach. The studied complexes in this work have 1:1, 1:2, 2:1, and 3:1 metal-ligand stoichiometry for all relevant Zn(II)-Rutin configurations. The least deviation between theoretical and experimental spectroscopic data was used as an initial criterion to select the probable candidate structures. Our theoretical spectroscopic results strongly indicate that the experimentally suggested modes of coordination (1:2 and 2:1) are likely to exist in solution, supporting the two distinct experimental findings in DMSO and methanol solution, which may be seen as an interesting result. Our predicted 1:2 and 2:1 metal complexes are in agreement with the experimental stoichiometry; however, they differ from the proposed structure. Besides the prediction of the coordination site and molecular structure in solution, an important contribution of this work is the determination of the OH-C5 deprotonation state of rutin due to metal complexation at the experimental conditions (pH = 6.7 and 7.20). We found that, in the two independent synthesis of metal complexes, distinct forms of rutin (OH-C5 and O(-)-C5) are present, which are rather difficult to be assessed experimentally.

Determinants of losses in the latent tuberculosis cascade of care in Brazil: A retrospective cohort study.

BACKGROUND: The present study evaluated factors associated with losses in the latent tuberculosis infection (LTBI) cascade of care in contacts of tuberculosis (TB) patients, in a referral center from a highly endemic region in Brazil. METHODS: Contacts of 1672 TB patients were retrospectively studied between 2009 and 2014. Data on TB screening by clinical investigation, radiographic examination and tuberculin skin test (TST) were extracted from medical records. Losses in the cascade of care and TB incidence within 2-year follow-up were calculated. RESULTS: From a total of 1180 TB contacts initially identified, only 495 were examined (58% loss), and 20 were diagnosed with active TB at this stage. Furthermore, 435 persons returned for TST result interpretation and 351 (∼81%) were TST positive. Among those with positive TST, 249 (73%) were treated with isoniazid for 6 months whereas 51 abandoned therapy early. Three individuals who did not receive LTBI treatment, one with incomplete treatment and another who completed treatment developed active TB. A logistic regression analysis revealed that increases in age were associated with losses in the LTBI cascade independent of other clinical and epidemiological characteristics. CONCLUSIONS: Major losses occur at initial stages and older patients are at higher risk of not completing the LTBI cascade of care.

Chemically Modified Carbon Nanohorns as Nanovectors of the Cisplatin Drug: A Molecular Dynamics Study.

Carbon nanohorns (CNH) have been considered potential anticancer drug carriers, such as the cisplatin drug (cddp), due to their low toxicity, high purity, drug-loading capacity, and biodegradation routes. However, when it comes to nanomedicine applications, chemical functionalization is an essential step in order to overcome undesirable properties of these nanomaterials, such as the high hydrophobicity, low reactivity, and low dispersibility in polar solvents. In this context, the present study involved the modeling of new CNH topologies based on chemical oxidation and reduction mechanisms and the investigation of the influence of these modified structures on the dynamics and stability of inclusion complexes with cddp. The results indicated that these functionalization strategies lead to the opening of nanowindows on the CNH surfaces, which would constitute the main route for drug release, as reported by experimentalists. Also, our results showed that the insertion of polar functional groups on the oxidized CNH (CNHox-N) contributed to an improvement of the cddp@CNHox-N biocompatibility due to the greater number of hydrogen bonds formed with the solvent. Despite the favorable formation of all complexes, the binding free energies pointed out that the oxidation process made the cddp@CNHox-N complexes slightly less stable than the ones with pristine and reduced CNH. Besides, the results suggest the possibility to tune the complex stability by controlling the oxidation degree, which could be explored by the experimentalists in order to design controlled drug delivery systems based on CNH nanocarriers.

Molecular dynamics of carbon nanohorns and their complexes with cisplatin in aqueous solution.

The medication with Pt-based antitumor drug cisplatin has demonstrated effective results against cancer cells, despite the severe side effects due to the high toxicity associated with the low selectivity of these anticancer agents. An alternative to overcome or decrease the side effects is to use drug delivery systems, which can carry high doses of the anticancer drug and promote its slow and targeted release to the tumor sites. Herein, we used molecular dynamics to study prototypes of the complexes formed by the encapsulated cisplatin and carbon nanohorns (CNH), with the purpose to characterize its structures and dynamical behavior in aqueous solution, an important feature to assess the potentiality of using CNH as carrier systems. The results indicated the presence of up to 36 water molecules inside the empty CNH cavity, depending on the cone angle and the presence of the cisplatin. Some of these solvent molecules are expelled out to the bulk upon cisplatin inclusion, although more than 10 molecules remain even for the narrow structures. Moreover, the calculated binding free energy (ΔbG) pointed out that the inclusion complexes formation between CNH structures and up to two cisplatin molecules was thermodynamically favorable in aqueous media, which suggests the potentiality of these carbon nanostructures as drug carriers. For the most likely and narrow host structure the average ΔbG was -92.0 kcal mol-1 for inclusion of two cisplatin, with most of the complex stability coming from the van der Waals contribution.

Chemical characteristics of a heteropolysaccharide from Tylopilus ballouii mushroom and its antioxidant and anti-inflammatory activities.

Fucogalactomannan (FGM) is a non-sulphated polysaccharide isolated from the Tylopilus ballouii mushroom. We investigated the chemical characteristics of this FGM using HPLC, chemical methods, and NMR studies ((1)H, (13)C, (1)H/(13)C-HSQC and DEPT-135 spectroscopies) without chemical fragmentation. This polysaccharide consisted primarily of mannose and galactose with variable amounts of fucose and traces of xylose and with MW of 140kDa. Infrared and NMR spectroscopies showed the possible interaction between these polysaccharides and proteins. The antioxidant activity showed for FGM a high inhibition of superoxide and hydroxyl radicals with an IC50 of 1.25 and 1.6mg/mL, respectively. The results of peroxidation tests showed that FGM had an IC50 of 1.72mg/mL. Furthermore, the anti-inflammatory assay showed that FGM reduced edema by 32.8%, 42.0%, and 56% at doses of 30, 50, and 70mg/kg, respectively. Thus, these results suggested a structure and indicated possible anti-inflammatory and antioxidant activities use of these polysaccharides.

DFT study of cisplatin@carbon nanohorns complexes.

This paper reports a quantum chemical investigation of the inclusion complex formation between a carbon nanohorn structure and cisplatin molecule, using the density functional theory (DFT) with the B3LYP functional and 6-31G(d,p)/LanL2DZ standard basis sets. The inclusion of the drug in host molecules such as carbon nanohorns (CNHs), aims to reduce the toxicity and enhance the effectiveness of cisplatin. In this work we carried out a search for minimum energy structures on the potential energy surface (PES) for CNH-cisplatin interaction, and then calculated the stabilization energy, charge distribution and NMR spectra, which can be of great aid for the experimental identification of the inclusion compound. Our results indicate that the CNH and cisplatin can indeed form stable inclusion complex, with the calculated (1)H NMR and (15)N NMR chemical shifts for cisplatin atoms revealing very substantial changes due to complex formation (~20ppm) that can be easily experimentally observed, which is helpful to the spectra assignment and the inclusion compound structural elucidation.