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Size, CD4 and CD8 marker profiles and functions of lymphocyte subpopulations in mucosal-associated lymph nodes.

We analyzed phenotypic and functional characteristics of T cell populations in mucosal-associated supramammary and mesenteric lymph nodes in goats. Here we demonstrate, by flow cytometry, quantitative differences in CD4 and CD8 T cell subsets among large and small mucosal-associated lymphocyte populations and their differential regulatory activities on resident lymph node B cells stimulated with Staphylococcus aureus Cowan I or pokeweed mitogen. The CD4/CD8 T cell ratio was lower in mesenteric lymph nodes (1.46) when compared to that of supramammary lymph nodes (2.18). Analysis of large and small lymphocyte subpopulations from lymph nodes showed nearly 62% of the lymphocytes from mesenteric lymph nodes being of large cell phenotype with CD4/CD8 ratios of 1.34. In contrast, large cell subpopulations in supramammary lymph nodes showed a significantly lower number (50%) with a higher CD4/CD8 ratio of 2.05. Functionally, mesenteric lymph node T cells, isolated by nylon wool, showed heightened suppressive activity in mitogen-driven B cell proliferation responses, whereas T cells from supramammary lymph nodes were stimulatory. These findings clearly demonstrate distinctive functional properties between resident T cell populations of supramammary and mesenteric lymph nodes, suggesting that different proportions of T cell subsets in these nodes are activated and thus regulate regional immune responses via different pathways.

Animals

Turner syndrome patients as adults: a study of their cognitive profile, psychosocial functioning and psychopathological findings.

In this study we collected data on the cognitive abilities, psychosocial adjustment and psychopathology of 20 non-institutionalized adult Turner syndrome patients. The majority of them had a normal intelligence, most were socially well adapted and no high prevalence of psychopathology was noted. In only one patient evidence of a serious bipolar hypomanic disorder and antisocial personality was found, and in one other an episode of anorexia nervosa. Nevertheless, 50% of the women expressed feelings of low self-confidence, depression and social insecurity i.e. achieving a mature level of psycho-social functioning remains a problem for a number of Turner individuals. In the counseling process of adult Turner patients special attention should be given to the social and psychological functioning so that intervention can be made if social awkwardness and psychological well-being becomes a problem.

Adaptation, Psychological

Metabolic reprogramming and taxonomic drivers in bacterial vaginosis: A large-scale metagenomic meta-analysis.

OBJECTIVE: Bacterial vaginosis (BV) represents a profound ecological shift from a Lactobacillus-dominated microbiota to a diverse polymicrobial biofilm associated with adverse outcomes. While taxonomic signatures are well-documented, the functional mechanisms driving this transition remain obscured. This study elucidates the genomic potential for metabolic reprogramming and the putative "functional handover" underpinning the stability of the dysbiotic state. METHODS: A computational meta-analysis of 3557 vaginal microbiomes from diverse global cohorts was performed using the standardized MGnify pipeline. A high-resolution subset of 187 whole-genome shotgun (WGS) metagenomes was stratified to compare functional potential across demographic groups. Taxon-function interaction networks were constructed, utilizing a dual-filter statistical approach (p&#x202f;<&#x202f;0.05 and effect size ranking), to map the shift from homeostatic maintenance to dysbiotic metabolic potential. RESULTS: BV was characterized by a fundamental shift from "maintenance" pathways to high-turnover "growth-oriented" genomic repertoires. While ABC transporter-like domains were present in healthy communities, dysbiosis was marked by a quantitative expansion and diversification of these systems alongside P-loop NTPases. Network analysis revealed a putative "functional handover": while Gardnerella serves as the adherent structural scaffold, the metabolic burden appears to be associated with secondary anaerobes, specifically BVAB1 and Sneathia, which exhibit strong genomic correlations with nutrient transport and stress response pathways. Crucially, microbiomes from women of African ancestry (Black cohort) exhibited a distinct functional profile with genomic signatures consistent with functions previously associated with resistome expansion (e.g., tetracycline/macrolide resistance), contrasting with Asian cohorts. CONCLUSION: BV is a state of metabolic reprogramming where genomic functional dominance is transferred from Lactobacillus to a cooperative network of anaerobic opportunists. Identifying BVAB1 and Sneathia as candidate metabolic engines, supported by a Gardnerella scaffold, challenges current therapeutic paradigms and highlights the potential for precision medicine targeting specific functional drivers and resistome profiles across diverse populations.

Humans

Fine structure of vesiculated nerve profiles in the human lumbar facet joint.

The ultrastructural features of vesiculated nerve profiles were examined within a perivascular plexus of unmyelinated nerve fibres around small arteries and arterioles in the posterior facet joint capsule. Such profiles were exclusively observed in the dense fibrous layer and the adjacent part of the subintimal layer. The ligamentum flavum lacked any type of innervation. The vesiculated nerve profiles were tentatively classified on the basis of the fine structural appearances of their vesicular content. Two major types of nerve profiles could readily be distinguished in the capsular tissue. Both displayed a variable number of mitochondria, neurotubules and neurofilaments. The first type, containing predominantly small vesicles with an electron-dense granule or core, was frequently encountered and considered to be adrenergic in function. Profiles similar in morphology were also observed in the synovial plical tissue. A second type of profile, found in the joint capsule, contained varying proportions of small agranular (clear) vesicles and mitochondria. Some of these profiles exhibited an accumulation of mitochondria and were considered to be sensory in function. Nerve profiles filled with predominantly small flattened vesicles were occasionally encountered.

Adult

A new description of the photon beam peak-depth profile as a function of field size.

The dose profile at peak depth in water is described as the product of an apparatus function and a source function. In principle, the source function is the circularly symmetric profile which would be measured at peak depth without any collimation. In practice, the peak-depth profile in the diagonal plane, measured for the largest collimator setting, is used for this purpose. The apparatus function represents the collimator acting upon the source function, and is referred to as the collimator function. The collimator function for any field size can be developed from the ratio of the peak-depth profile for a single medium-sized field and the source function. The method has been tested for a set of irregularly flattened 4-MV x-ray beams as well as for practically flat 15-MV x-ray beams. The model requires as basic data only three peak-depth profiles: one in each principal plane of a medium-sized square field and the peak-depth profile in the diagonal plane for the largest field. It replaces the peak-depth transformation in the projective beam model.

Humans

Imaging-Guided Omics Technologies for Resolving Rare Cancer States and Advancing Nanomedicine.

The ability to resolve rare and transient cellular states is critical for understanding metastasis, immune evasion, and therapy resistance in cancer, yet these dynamic processes often escape detection by conventional sequencing and imaging approaches. Recent advances at the interface of nanotechnology, high-resolution live-cell imaging, and single-cell/spatial multiomics methods have enabled functional profiling of cells with unprecedented precision within their native microenvironment. In this Mini-Review, we highlight emerging nanoscale platforms that couple real-time phenotypic imaging with molecular readouts, such as FUNseq and CIN-seq, to directly link functional heterogeneity to transcriptomic, proteomic, and epigenomic information. By integrating nanoscale optical imaging, microengineered perturbation tools, and AI-driven computational analysis, these technologies open up new avenues for dissecting rare metastatic, therapy-resistant, or immune-evasive subpopulations. We further discuss how these next-generation imaging-guided single-cell and spatial omics platforms not only advance fundamental cancer biology but also create opportunities to accelerate the development of nanomedicine applications.

Humans

Genetic profile of the transcriptional signals from the adenovirus major late promoter.

Identical functional profiles were obtained for in vivo and in vitro transcription assays of more than 30 site-directed point mutants within the adenovirus major late promoter. The functional limits of the functional regions encompassing upstream promoter element are defined (-51 to -61), as well as a region around the transcription start site (-1 to +1), flanked by regions insensitive to sequence alterations.

Adenoviridae

The role of pharmacological profiling in safety assessment.

The profiling of new drug candidates for general pharmacological properties requires a systematic examination of the functional effects of agents in a variety of in vitro and in vivo assays. Both the behavioral and physiological consequences of drug treatment are monitored in models of central nervous system, cardiovascular, autonomic, gastrointestinal, and renal functions. Broad functional profiling provides valuable information to the preclinical pharmacologist with respect to the selectivity of new agents and may serve to identify new and useful therapeutic indications of investigational drugs. At the same time, knowledge of the effects on these physiological systems can also play an important role in safety assessment. Pharmacological activity of a new agent that is both unintended and undesirable can be referred to as "pharmacological toxicity." In general, the spectrum of toxicities disclosed in pharmacological profiling includes a variety of acute functional or physiological effects which are not life-threatening and are readily reversible. On rare occasions, unanticipated and life-threatening pharmacological effects (e.g., convulsions, arrhythmias) are detected which can seriously detract from the usefulness of a new agent and may therefore deter the drug development process. It should also be noted that repeated exposure to acute pharmacological effects may lead to less obvious chronic findings, such as target organ effects or tumor formation in animals. The interpretation of pharmacological toxicity with respect to the safety profile of a new drug candidate is dependent not only upon the types of reactions observed and the doses at which they occur but also upon the nature of the effects elicited as to whether they represent expected extensions of the primary mechanism of action of a compound or constitute reactions unrelated to the primary pharmacological activity. The ultimate impact of pharmacological toxicity, as with all adverse findings in preclinical assessment, is dependent upon the projected therapeutic margin of safety as well as the risk-to-benefit ratio for new drug entities. In addition to supplementing the existing armamentarium of preclinical safety studies, pharmacological profiling can also play an important role in (1) the selection of new drug candidates with reduced toxic potential, (2) the design and conduct of preclinical toxicology studies, (3) the investigation of preclinical and clinical safety issues, and (4) the identification of potential functional effects to be monitored most closely in clinical trials of new drug entities.

Animals

Return to work after rehabilitation following traumatic brain injury.

The relationship of medical variables and discharge functional status to vocational and educational outcomes was examined in 79 closed head-injured patients who were consecutively admitted to an inpatient rehabilitation hospital during a two-year period. A follow-up study, conducted after hospital discharge (median, 16.5 months), found that 66% (n = 52) of the patients had returned to work or school, while 34% (n = 27) did not. Patients were divided into return and non-return to work groups. Traditional variables included age, severity of brain-damage as characterized by CT head scan, duration of post-traumatic amnesia, duration of coma, length of stay and acute inpatient rehabilitation program. Discharge functional scores were analysed by t-tests and chi-square analysis. Results suggest that traditional factors of younger age, shorter length of coma, minimal CT head scan findings and shorter length of stay were significant contributors to educational/vocational outcome. Their significance was enhanced by discharge functional profile measurement of medical, physical and psychological/neuropsychological integrity. Those functional measures not significant were in social, vocational, recreational and communication areas. These factors may continue to improve over a longer period of time and should be tracked in the post-acute rehabilitation phase for their significance in return to work/school.

Activities of Daily Living

[Automated information system for management of an outpatient hospital].

The development of the organization and functional model of an outpatient hospital of a therapeutic profile functioning as a department of an outpatient clinic prompted the author to create an automated information system for the collection, analysis, and storage of medical information using personal computers. This will make medicostatistical information available for heads of institutions and departments and offer variants of management decisions on improving the management and function of therapeutic outpatient hospitals.

Ambulatory Care

Plasma morphine and glucuronide (M3G and M6G) concentrations in hospice inpatients.

Plasma morphine, morphine-3-glucuronide (M3G), and morphine-6-glucuronide (M6G) concentrations were quantified by high performance liquid chromatography (HPLC) in 36 hospice inpatients receiving morphine orally or subcutaneously. The data were analyzed in relation to dose, serum creatinine, serum gamma glutamyl transferase, and presence or absence of opioid-induced adverse effects. There were significant associations (P < 0.05) between plasma morphine, M3G (subcutaneous route only), and M6G concentrations and dose for both routes of administration. The mean dose-corrected plasma morphine concentration for the subcutaneous group was three times that of the oral group, confirming present oral to subcutaneous dose conversion practices. Nineteen patients experienced symptoms attributed to morphine: nausea and vomiting in ten and acute delirium in nine. Serum creatinine was elevated in patients with adverse effects (P = 0.031), as were the dose-corrected plasma M3G (P = 0.029) and M6G (P = 0.043) concentrations. All seven patients with serum creatinine concentrations above the normal range had symptoms attributed to opioid-induced adverse effects. Plasma M3G, M6G, and dose-corrected plasma M3G and M6G concentrations were significantly (P < 0.001) higher in these patients than in those with normal serum creatinine concentrations. The data indicate that accumulation of M3G and M6G may be a causal or aggravating factor in the nausea and vomiting and cognitive function profile of palliative and terminal care patients with significant renal function impairment.

Adult

Functional and neutralization profile of seven overlapping antigenic sites on the HN glycoprotein of Newcastle disease virus: monoclonal antibodies to some sites prevent viral attachment.

We have previously identified five antigenic sites on the hemagglutinin-neuraminidase (HN) glycoprotein of the Australia-Victoria isolate of Newcastle disease virus (Iorio and Bratt, J. Virol. 48, 440-450; Iorio et al., J. Gen. Virol. 67, 1393-1403). Two additional sites (designated 12 and 23) are now described, bringing to a total of seven the number of antigenic sites defined by our panel of neutralizing anti-HN antibodies. Competition antibody binding and additive neutralization assays reveal that each of these newly-identified sites overlaps two previously-defined ones. The seven HN antigenic sites thus form a continuum in the three-dimensional conformation of the molecule. Studies on the inhibition of hemagglutination (HA), neuraminidase (NA) and the attachment of virus to chick cell monolayers have been used to construct a functional profile of each antigenic site. Monoclonal antibodies (mAbs) to three overlapping sites (12, 2 and 23) inhibit HA and NA and prevent viral attachment to chick cell monolayers. These findings are consistent with the domains recognized by these mAbs being close to the NA and receptor-binding sites. MAbs to two other overlapping sites, 14 and 1 (which in turn, overlap site 12), inhibit HA quite effectively, and attachment to a lesser extent. Sites 14 and 1 probably identify a second domain involved in receptor recognition. MAbs to the two remaining sites (3 and 4), though neutralizing, are negative in all three assays, thus recognizing domains not involved in HA or NA or attachment to chick cells.

Animals

The immediate effect of colposuspension on resting and stressed urethral pressure profiles in anaesthetized incontinent bitches.

The aim of this study was to document what changes in the resting and stressed urethral pressure profile occur in the incontinent bitch with urethral sphincter mechanism incompetence (SMI) immediately after colposuspension. Resting and stressed subtracted simultaneous urethral pressure profilometry was performed immediately pre- and postcolposuspension in 26 bitches diagnosed with SMI. All of the urethral pressure profiles were measured in anaesthetized bitches using a standard technique and two orientations of the catheter transducers (dorsal and left). Readable pre- and postoperative urethral pressure profiles were obtained in 20 of the 26 bitches. Subjective and objective evaluation of the profiles showed significant differences in the profiles pre- and postcolposuspension. Immediately postoperatively there were significant (P < .05) increases in functional profile length, maximum urethral closure pressure (MUCP), and distance between the bladder neck and the first negative respiratory peak and stressed spike. There was a significant (P < .001) decrease in the percentage of negative spikes extending below the resting intravesical pressure on the subtracted profile. The pressure transmission profiles were significantly (P < .001) altered by surgery. The findings presented support the hypothesis that colposuspension may restore continence by increasing pressure transmission to the proximal urethra and bladder neck. The results also suggest that immediately after surgery functional urethral length and urethral resistance are increased.

Analysis of Variance