Undescended Testes Growth Potential in Relation to Testis Position from Diagnosis until Puberty.

Background: Testicular volume (TV) and testicular atrophy index (TAI) were used to determine criteria for normal, hypotrophic and atrophic undescended testes (UDT). Objectives: This study aimed to determine changes in TV and TAI in patients with different types of UDT. Materials and Methods: 182 boys (aged 0.3-14.0 years) with 212 UDTs were assessed twice 24 months apart. Testes were unilateral (UCT) or bilateral canalicular (BCT) and intra-abdominal (IAT). Results: At the beginning of the observation, the highest TAI was observed in IAT and the lowest in the BCT group (38.1 vs. 12.5%, p < 0.05). After 2 years, the highest TAI was observed in the BCT and IAT groups (20.5 and 19.1%), while the lowest was in the UCT group (12.0%, p < 0.05). At the beginning and after 2 years, the highest TAI was observed in boys aged < 6 years (25.0%, 18.2%) and the lowest in pubertal boys aged 12-14 years (5.9%, 7.3%, p < 0.05). A total of 78.3% of patients at the beginning and 86.8% at the end of the observation had TAI < 30%. Furthermore, 7% of boys at the beginning and 3% at the end of the observation had TAI > 50%. IATs have the highest testicular growth potential (TGP), while BCTs have the lowest (120.0 vs. 28.6%, p < 0.05). The highest TGP was in boys aged < 3 years (100%, p < 0.05) and boys aged 12-14 years (98.1%, p < 0.05), while the lowest was in boys aged 9-10.9 years (19.5%, p < 0.05). Conclusions: We revealed the continuous growth of UDTs until puberty independently of their position. IATs revealed high growth potential.

Hydrogen-atom tunneling in small thioamides: N-methylthiourea, thiobenzamide and 2-cyanothioacetamide.

The most stable thione tautomeric forms of N-methylthiourea, thiobenzamide and 2-cyanothioacetamide were isolated in low-temperature argon matrices. The higher-energy thiol tautomers of these compounds were generated upon irradiation of matrix-isolated monomers with UV (λ > 270 nm) light. For N-methylthiourea and thiobenzamide, kept in the dark at 3.5 K for a long period of time, a spontaneous thiol â†’ thione hydrogen atom tunneling transformation occurred. Only the thiol isomers with the favorably oriented hydrogen atom of the imino group underwent these hydrogen-atom tunneling processes. The other thiol isomers, with the hydrogen atom of the imino group oriented towards the sulfur atom, did not undergo the thiol â†’ thione conversion. For the photogenerated thiol forms of 2-cyanothioacetamide, no spontaneous thiol â†’ thione tautomeric transformation was detected. Instead, only the spontaneous conformational change of one S-H rotamer of the thiol 2-cyanothioacetamide tautomer into the other S-H rotamer was observed.

Changes in Oral Health and Dental Esthetic in Smokers Switching to Combustion-Free Nicotine Alternatives: Protocol for a Multicenter and Prospective Randomized Controlled Trial.

BACKGROUND: Although the detrimental effects of conventional combustible cigarettes on oral health and dental esthetics are well known, there is limited information about the long-term impact of combustion-free nicotine alternatives (C-F NA) such as e-cigarettes or heated tobacco products. OBJECTIVE: This multicenter, prospective, 3-parallel-arm randomized controlled trial will investigate whether switching from combustible cigarettes to C-F NA will lead to measurable improvements in oral health parameters and dental esthetics over 18 months in adult smokers with limited gum disease. METHODS: Regular smokers not intending to quit and without clinical signs of periodontitis will be randomly assigned (1:4 ratio) to either standard of care with brief cessation advice (control group; arm A) or C-F NA use (intervention group; arm B). The study will also include a reference group of never smokers (reference group; arm C). The primary end point is the change in the Modified Gingival Index (MGI) score from baseline between the control arm (arm A) and the intervention arm (arm B) at the 18-month follow-up. In addition, the study will analyze the within- and between-group (arms A, B, and C) changes in MGI assessment, plaque imaging, dental shade quantitation, tooth stain scores, and oral health-related quality of life questionnaires measured at each study time point. All participants will attend a total of 7 clinic visits: screening, enrollment, and randomization (visit 0); baseline visit-day 14 (visit 1); day 90 (visit 2); day 180 (visit 3); day 360 (visit 4); and day 540 (visit 5). This multicenter study will be conducted in 4 dental clinics in 4 countries. The statistical analysis will involve descriptive statistics for continuous and categorical data. Primary end points will undergo tests for normality and, based on distribution, either a 2-sided t test or Mann-Whitney U test. Linear mixed model with random factors center and study arms by center will also be applied. Secondary end points, including MGI assessment and quality of life, will be subjected to similar tests and comparisons. Only if one value of the parameter MGI is missing after day 1, the last available observation will be carried forward. The analysis will be performed on the substituted data. Secondary parameters will not have missing value replacement. RESULTS: Participant recruitment began in October 2021, and enrollment was completed in June 2023. Results will be reported in 2025. CONCLUSIONS: This will be the first study to provide key insights into oral health benefits or risks associated with using C-F NA in smokers who are seeking alternatives to cigarette smoking. TRIAL REGISTRATION: ClinicalTrials.gov NCT04649645; https://clinicaltrials.gov/ct2/show/NCT04649645. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/53222.

Metronidazole Cocrystal Polymorphs with Gallic and Gentisic Acid Accessed through Slurry, Atomization Techniques, and Thermal Methods.

In this study, key features of metronidazole (MNZ) cocrystal polymorphs with gallic acid (GAL) and gentisic acid (GNT) were elucidated. Solvent-mediated phase transformation experiments in 30 solvents with varying properties were employed to control the polymorphic behavior of the MNZ cocrystal with GAL. Solvents with relative polarity (RP) values above 0.35 led to cocrystal I°, the thermodynamically stable form. Conversely, solvents with RP values below 0.35 produced cocrystal II, which was found to be only 0.3 kJ mol-1 less stable in enthalpy. The feasibility of electrospraying, including solvent properties and process conditions required, and spray drying techniques to control cocrystal polymorphism was also investigated, and these techniques were found to facilitate exclusive formation of the metastable MNZ-GAL cocrystal II. Additionally, the screening approach resulted in a new, high-temperature polymorph I of the MNZ-GNT cocrystal system, which is enantiotropically related to the already known form II°. The intermolecular energy calculations, as well as the 2D similarity between the MNZ-GAL polymorphs and the 3D similarity between MNZ-GNT polymorphs, rationalized the observed transition behaviors. Furthermore, the evaluation of virtual cocrystal screening techniques identified molecular electrostatic potential calculations as a supportive tool for coformer selection.

Scale-free correlations in the dynamics of a small (N∼10000) cortical network.

The advent of novel optogenetics technology allows the recording of brain activity with a resolution never seen before. The characterization of these very large data sets offers new challenges as well as unique theory-testing opportunities. Here we discuss whether the spatial and temporal correlations of the collective activity of thousands of neurons are tangled as predicted by the theory of critical phenomena. The analysis shows that both the correlation length ξ and the correlation time τ scale as predicted as a function of the system size. With some peculiarities that we discuss, the analysis uncovers evidence consistent with the view that the large-scale brain cortical dynamics corresponds to critical phenomena.

High neutrophil-to-lymphocyte ratio (NLR) predicts poor response to intravenous thrombolysis in white Caucasian stroke patients.

OBJECTIVES: Our aim was to investigate usefulness of the neutrophil-to-lymphocyte ratio (NLR) for predicting poor response to intravenous rtPA in white Caucasian ischemic stroke patients treated within 4.5 hours from the onset. MATERIALS AND METHODS: This retrospective analysis included all consecutive acute ischemic stroke patients (N = 344) treated with rtPA in a tertiary stroke center from 2011 to 2017. NLR was calculated from complete blood counts obtained on admission. The patients were classified into NLR terciles (T1 <1.75, T2<2.97, T3≥2.97). Significant neurological improvement was defined as an 8-point reduction in the NIHSS score or reaching the score of 0 to 1. RESULTS: Compared to NLR T1, patients from NLR T3 were significantly older, more often disabled before stroke, and had longer onset-to-needle time. They less often achieved neurological improvement at day 7 (38% vs 59% p=0.002) and had higher 90-day mortality (27% vs 13%, p=0.020), with no differences in neurological improvement at 24 hours, occurrence of sICH and 7-day mortality. Each additional 4 units of NLR decreased unadjusted and adjusted odds for achieving favorable outcome at day 7 (OR 0.65, 95% CI: 0.46-0.92; aOR 0.62, 95% CI: 0.39-1.00), and increased the odds for death at 3 months (OR 1.60, 95% CI: 1.15-2.24; aOR 1.82, 95% CI:1.14-2.92) CONCLUSIONS: High NLR can predict poor response to intravenous rtPA in Caucasian patients with acute ischemic stroke, especially in terms of not achieving significant neurological improvement at day 7 and death at day 90. It encourages attempts to incorporate NLR in already validated scores.

Probing fluconazole deposition inside mesoporous silica using solid-state NMR spectroscopy: Crystallization of a confined metastable form and phase transformations under storage conditions.

Encapsulation of molecules into mesoporous silica carriers continues to attract considerable interest in the area of drug delivery and crystal engineering. Here, MCM-41, SBA-15 and MCF silica matrices were used to encapsulate fluconazole (FLU), a pharmaceutically relevant molecule with known conformational flexibility, using the melting method. The composites have been characterized using 1H, 13C and 19F NMR spectroscopy, nitrogen adsorption, PXRD and thermal analysis (DSC, TGA). Drug loading up to 50 wt% allowed us to probe the crystallization process and to detect different local environments of confined FLU molecules. 19F NMR spectroscopy enabled us to detect the gradual pore filling of silica with FLU and differentiate the amorphous domains and surface species. The use of the complementary structural and thermal techniques enabled us to monitor crystallization of the metastable FLU form II in MCF. Using 1H and 19F NMR spectroscopy we observed pore-size dependent reversible dehydration/hydration behaviour in the MCM and SBA composites. As water content has considerable importance in understanding of physicochemical stability and shelf-life of pharmaceutical formulations, experimental evidence of the effect of API-water-carrier interactions on the API adsorption mechanism on silica surface is highlighted.

Photoinduced Long-Distance Hydrogen-Atom Transfer in Molecules with a 7-Hydroxyquinoline Frame and a Carbaldehyde or Aldoxime Group as the Intramolecular Hydrogen Transporting Crane.

The photochemical properties of monomeric 7-hydroxyquinoline substituted at position 8 with carbaldehyde or aldoxime groups were studied for the molecules isolated in solid Ar low-temperature matrices (at 10 K). It was experimentally demonstrated that upon UV excitation, both carbaldehyde and aldoxime groups act as intramolecular cranes transmitting hydrogen atoms from the hydroxyl group to the remote nitrogen atom of the quinoline ring. Furthermore, in the case of 7-hydroxyquinoline-8-aldoxime (and its derivatives), the second photochemical channel was activated upon UV (λ > 360 nm) excitation. This process involves syn-anti isomerization around the double C═N bond in the aldoxime group. The structures of the reactant hydroxy tautomeric form and the photoproduced isomers of the studied molecules were unequivocally determined by means of IR spectroscopy combined with theoretical predictions of the IR spectra of the candidate structures.

Reliability of the modified Rankin Scale in clinical practice of stroke units and rehabilitation wards.

Introduction: The Modified Rankin Scale (mRS) is the most common tool to quantify post-stroke disability in everyday practice and by certified raters in clinical trials. However, interobserver variability may affect reliability of retrospective observational studies, including clinical registries. Our aim was to assess real-life consistency between neurologists and physical and rehabilitation medicine physicians using mRS to rate post-stroke disability of patients transferred directly from stroke unit (SU) to rehabilitation ward (RW). Methods: This is a retrospective analysis of 132 consecutive acute stroke patients transferred from single tertiary SU to RW located in the same hospital in Poland. Patients were assessed by one rater from each department at the day of transfer. We distinguished between physicians previously certified in using mRS for clinical trials and not-certified physicians using mRS in everyday practice. Results: mRS at discharge from SU and on admission to RW was recorded for 105 of 132 patients. The overall agreement was 70.5% (kappa 0.55). Similar agreement was observed in the subset of 30 patients rated by certified physicians in both departments (70.0%, kappa 0.57) and in the subset of 61 patients rated by a pair of certified neurologist and not-certified rehabilitation physician (73.8%, kappa 0.58). Conclusions: Everyday consistency between raters from SU and RW in using mRS is modest as in previous validation studies. However, it may be considered sufficient for the purpose of observational studies or stroke registries. It emphasizes the need for easily accessible training in conventional mRS or implementation of specialized tools with predefined questions.

Support for the Vulnerability Management Process Using Conversion CVSS Base Score 2.0 to 3.x.

COVID-19 forced a number of changes in many areas of life, which resulted in an increase in human activity in cyberspace. Furthermore, the number of cyberattacks has increased. In such circumstances, detection, accurate prioritisation, and timely removal of critical vulnerabilities is of key importance for ensuring the security of various organisations. One of the most-commonly used vulnerability assessment standards is the Common Vulnerability Scoring System (CVSS), which allows for assessing the degree of vulnerability criticality on a scale from 0 to 10. Unfortunately, not all detected vulnerabilities have defined CVSS base scores, or if they do, they are not always expressed using the latest standard (CVSS 3.x). In this work, we propose using machine learning algorithms to convert the CVSS vector from Version 2.0 to 3.x. We discuss in detail the individual steps of the conversion procedure, starting from data acquisition using vulnerability databases and Natural Language Processing (NLP) algorithms, to the vector mapping process based on the optimisation of ML algorithm parameters, and finally, the application of machine learning to calculate the CVSS 3.x vector components. The calculated example results showed the effectiveness of the proposed method for the conversion of the CVSS 2.0 vector to the CVSS 3.x standard.

What Has Immunology Brought to Periodontal Disease in Recent Years?

Recent decades have shed a new light on the pathomechanism of periodontal inflammation. While classic periodontology concentrates on biofilm control, oral hygiene improvement, professional tooth cleaning and surgical correction of damaged periodontal tissues, new aspects of the destruction mechanisms are being raised. Among them, the greatest attention is paid to the influence of host response on the clinical manifestations of the disease. Numerous studies have proved that the shift from gingivitis to periodontitis is not a simple progress of the disease, but an event occurring only in susceptible individuals. Susceptibility may result from appearance of local factors facilitating biofilm accumulation and/or maturation, or from systemic features, among which over-reaction and prolonged agitation of non-specific component of inflammatory response is crucial. The present paper summarizes the association between periodontology and immunology and updates the knowledge accrued mostly in the recent years. After a brief explanation of advances in understanding of the disease aetiology, the most studied and potentially viable immunological markers of periodontal disease are presented. Possible new therapeutic strategies, exploiting knowledge about the nature of host response-immunomodulation and reduction of chronic oxidative stress-are also presented.

Molecular Level Characterisation of the Surface of Carbohydrate-Functionalised Mesoporous silica Nanoparticles (MSN) as a Potential Targeted Drug Delivery System via High Resolution Magic Angle Spinning (HR-MAS) NMR Spectroscopy.

Atomistic level characterisation of external surface species of mesoporous silica nanoparticles (MSN) poses a significant analytical challenge due to the inherently low content of grafted ligands. This study proposes the use of HR-MAS NMR spectroscopy for a molecular level characterisation of the external surface of carbohydrate-functionalised nanoparticles. MSN differing in size (32 nm, 106 nm, 220 nm) were synthesised using the sol-gel method. The synthesised materials displayed narrow particle size distribution (based on DLS and TEM results) and a hexagonal arrangement of the pores with a diameter of ca. 3 nm as investigated with PXRD and N2 physisorption. The surface of the obtained nanoparticles was functionalised with galactose and lactose using reductive amination as confirmed by FTIR and NMR techniques. The functionalisation of the particles surface did not alter the pore architecture, structure or morphology of the materials as confirmed with TEM imaging. HR-MAS NMR spectroscopy was used for the first time to investigate the structure of the functionalised MSN suspended in D2O. Furthermore, lactose was successfully attached to the silica without breaking the glycosidic bond. The results demonstrate that HR-MAS NMR can provide detailed structural information on the organic functionalities attached at the external surface of MSN within short experimental times.

Testicular, Epididymal and Vasal Anomalies in Pediatric Patients with Cryptorchid Testes and Testes with Communicating Hydrocele.

The goal of this study was to determine the prevalence of the testicular, epididymal, and vasal anomalies (TEVA) in cryptorchid and communicating hydrocele pediatric patients. Six hundred and ninety-one prepubertal boys underwent inguinal exploration for 741 undescended (UDT) or hydrocele testes. Two hundred and fifty-five TEVA were detected in 154 UDT boys, compared to 32 defects in 24 hydrocele patients (p < 0.001). The TEVA were more frequent in bilateral UDT (p = 0.009). Multiple defects were observed more frequently in the intra-abdominal testicles (p = 0.028). A correlation was found between the testicular atrophy index (TAI) and the incidence and number of TEVA in the UDT boys (p < 0.001). The smaller the testis (higher TAI), the more the defects that appeared in it and the higher the frequency of their appearance. Another correlation was established between testis position and the incidence and number of TEVA (p < 0.001). The higher the testis position, the more the defects that appeared in it and the higher the frequency of their appearance. A correlation was established between the position and the volume of the affected testis (p < 0.001). The higher the gonad position, the more severe the atrophy observed in it. The TEVA were more frequent in the UDT boys than in the hydrocele patients. We revealed that the risk of abnormal fusion between the testis, epididymis, and vas deferens is connected with the testis position (intra-abdominal testes) and bilateral non-descent.

Assessing Urban Policies in a COVID-19 World.

The aim of this study was to identify how the literature analyzes (identifies, evaluates, forecasts, etc.) the relationship between health issues and urban policy in relation to the COVID-19 pandemic. Four main levels were identified in these cases: (1) direct demands for changes in health care, (2) social issues, (3) spatial organization and (4) redefining the tasks of public authority in the face of identified challenges. The basic working method used in the study assumed a critical analysis of the literature on the subject. The time scope of the search covered articles from January 2020 to the end of August 2021 (thus covering the period of three pandemic waves). Combinations of keywords in the titles were used to search for articles. The health perspective pointed to the need for urban policies to develop a balance between health and economic costs and for coordination between different professionals/areas. A prerequisite for such a balance in cities is the carrying out of social and spatial analyses. These should illustrate the diversity of the social situations in individual cities (and more broadly in urban areas, including, sometimes, large suburbs) and the diversity's relationship (both in terms of causes and consequences) to the severity of pandemics and other health threats.

Association between Maternal Periodontitis and Development of Systematic Diseases in Offspring.

Periodontal disease (PD) is one of the most common oral conditions affecting both youths and adults. There are some research works suggesting a high incidence of PD in pregnant women. As an inflammatory disease of bacterial origin, PD may result in the activation of the pathways affecting the course and the pregnancy outcome. The authors, based on the literature review, try to answer the PICO question: Does maternal periodontitis (exposure) influence the incidence of complications rates in pregnancy and the development of systemic diseases in childhood and adult offspring (outcome) in the humans of any race (population) compared to the offspring of mothers with healthy periodontium (comparison)? The authors try to describe the molecular pathways and mechanisms of these interdependencies. There is some evidence that maternal periodontitis may affect the pregnancy course and outcome, resulting in preeclampsia, preterm delivery, vulvovaginitis and low birth weight. It can be suggested that maternal periodontitis may affect offspring epigenome and result in some health consequences in their adult life.

Directing Crystallization Outcomes of Conformationally Flexible Molecules: Polymorphs, Solvates, and Desolvation Pathways of Fluconazole.

Control over polymorphism and solvatomorphism in API assisted by structural information, e.g., molecular conformation or associations via hydrogen bonds, is crucial for the industrial development of new drugs, as the crystallization products differ in solubility, dissolution profile, compressibility, or melting temperature. The stability of the final formulation and technological factors of the pharmaceutical powders further emphasize the importance of precise crystallization protocols. This is particularly important when working with highly flexible molecules with considerable conformational freedom and a large number of hydrogen bond donors or acceptors (e.g., fluconazole, FLU). Here, cooling and suspension crystallization were applied to access polymorphs and solvates of FLU, a widely used azole antifungal agent with high molecular flexibility and several reported polymorphs. Each of four polymorphic forms, FLU I, II, III, or IV, can be obtained from the same set of alcohols (MeOH, EtOH, isPrOH) and DMF via careful control of the crystallization conditions. For the first time, two types of isostructural channel solvates of FLU were obtained (nine new structures). Type I solvates were prepared by cooling crystallization in Tol, ACN, DMSO, BuOH, and BuON. Type II solvates formed in DCM, ACN, nPrOH, and BuOH during suspension experiments. We propose desolvation pathways for both types of solvates based on the structural analysis of the newly obtained solvates and their desolvation products. Type I solvates desolvate to FLU form I by hydrogen-bonded chain rearrangements. Type II solvates desolvation leads first to an isomorphic desolvate, followed by a phase transition to FLU form II through hydrogen-bonded dimer rearrangement. Combining solvent-mediated phase transformations with structural analysis and solid-state NMR, supported by periodic electronic structure calculations, allowed us to elucidate the interrelations and transformation pathways of FLU.

The Effectiveness of a Bioactive Healing Abutment as a Local Drug Delivery System to Impact Peri-Implant Mucositis: A Prospective Case Series Study.

Modern dental therapy makes use of prosthetic implant reconstructions, which are supported or retained on dental implants. The most frequent, long-term complications associated with these prosthetic implants include mucositis and peri-implantitis. Since mucositis is the initial inflammation of tissues supporting the dental implant, the management of this condition is thus crucial. The aim of the present study was to assess the effects of the placement of bioactive healing abutment for 48 h, in patients diagnosed with peri-implant mucositis. Moreover, the quantitative and qualitative shift in the bacterial profile of the biofilm present in the peri-implant pockets, was assessed by means of RT-PCR genotyping. Each patient was examined using a commercially available PET test protocol: the first sample was taken upon diagnosis (after which the bioactive healing abutment, with clindamycin at a dose of 30 mg, was used for 48 h and replaced with the prosthetic superstructure used so far by a patient); the second sample was taken two weeks after removal of the bioactive healing abutment. The effects of the intervention were clinically assessed using the PET test after the two weeks. A significant reduction in mucositis was observed following treatment, as measured by periodontal indices: modified Sulcus Bleeding Index­mBI (p < 0.001), modified Plaque Index­PLI (r = 0.69, Z= −4.43; p < 0.001) and probing depth­PD (Z = −4.61; p < 0.001). Significant differences in the occurrence of periopathogenic bacteria were also observed: Aggregatibacter actinomycetemcomitans (p < 0.014; Z = −2.45; r = 0.38), Treponema denticola (p < 0.005; Z = −2.83; r = 0.44), Tannerella forsythia (p < 0.001; Z = −4.47; r = 0.69) and Porphyromonas gingivalis (p < 0.132; Z = −1.51).

Eikonal formulation of large dynamical random matrix models.

The standard approach to dynamical random matrix models relies on the description of trajectories of eigenvalues. Using the analogy from optics, based on the duality between the Fermat principle (rays) and the Huygens principle (wavefronts), we formulate the Hamilton-Jacobi dynamics for large random matrix models. The resulting equations describe a broad class of random matrix models in a unified way, including normal (Hermitian or unitary) as well as strictly non-normal dynamics. This formalism applied to Brownian bridge dynamics allows one to calculate the asymptotics of the Harish-Chandra-Itzykson-Zuber integrals.

Interactive Multiobjective Procedure for Mixed Problems and Its Application to Capacity Planning.

A problem that appears in many decision models is that of the simultaneous occurrence of deterministic, stochastic, and fuzzy values in the set of multidimensional evaluations. Such problems will be called mixed problems. They lead to the formulation of optimization problems in ordered structures and their scalarization. The aim of the paper is to present an interactive procedure with trade-offs for mixed problems, which helps the decision-maker to make a final decision. Its basic advantage consists of simplicity: after having obtained the solution proposed, the decision-maker should determine whether it is satisfactory and if not, how it should be improved by indicating the criteria whose values should be improved, the criteria whose values cannot be made worse, and the criteria whose values can be made worse. The procedure is applied in solving capacity planning treated as a mixed dynamic programming problem.