Evaluating the Long-Term Outcomes of Periodontal Surgery vs. Non-Surgical Treatment in Aggressive Periodontitis.

Background: Aggressive periodontitis is a severe form of periodontal disease characterized by rapid tissue destruction and tooth loss. The optimal treatment approach for managing this condition remains a topic of debate. Materials and Methods: A retrospective cohort study was conducted, involving patients diagnosed with aggressive periodontitis who received either surgical or non-surgical treatment between 2010 and 2020. Clinical and radiographic data were collected at baseline and regular intervals over a 5-year follow-up period. Surgical interventions included flap surgery, guided tissue regeneration, and bone grafting, while non-surgical treatments comprised scaling and root planning with or without adjunctive antibiotics. The primary outcomes assessed included changes in probing depth, clinical attachment level, tooth loss, and patient-reported quality of life measures. Results: A total of 120 patients were included in the study, with 60 patients in each treatment group. The surgical group demonstrated significantly greater reductions in probing depth and gains in clinical attachment level compared to the non-surgical group (P < 0.05). Tooth loss was significantly lower in the surgical group over the 5 years (P < 0.01). Patient-reported outcomes also favored the surgical group, with improved oral health-related quality of life. However, the surgical group had a higher incidence of postoperative complications. Conclusion: This study suggests that periodontal surgery yields superior long-term outcomes in the management of aggressive periodontitis compared to non-surgical treatment.

Managing COVID-19 within and across health systems: why we need performance intelligence to coordinate a global response.

BACKGROUND: The COVID-19 pandemic is a complex global public health crisis presenting clinical, organisational and system-wide challenges. Different research perspectives on health are needed in order to manage and monitor this crisis. Performance intelligence is an approach that emphasises the need for different research perspectives in supporting health systems' decision-makers to determine policies based on well-informed choices. In this paper, we present the viewpoint of the Innovative Training Network for Healthcare Performance Intelligence Professionals (HealthPros) on how performance intelligence can be used during and after the COVID-19 pandemic. DISCUSSION: A lack of standardised information, paired with limited discussion and alignment between countries contribute to uncertainty in decision-making in all countries. Consequently, a plethora of different non-data-driven and uncoordinated approaches to address the outbreak are noted worldwide. Comparative health system research is needed to help countries shape their response models in social care, public health, primary care, hospital care and long-term care through the different phases of the pandemic. There is a need in each phase to compare context-specific bundles of measures where the impact on health outcomes can be modelled using targeted data and advanced statistical methods. Performance intelligence can be pursued to compare data, construct indicators and identify optimal strategies. Embracing a system perspective will allow countries to take coordinated strategic decisions while mitigating the risk of system collapse.A framework for the development and implementation of performance intelligence has been outlined by the HealthPros Network and is of pertinence. Health systems need better and more timely data to govern through a pandemic-induced transition period where tensions between care needs, demand and capacity are exceptionally high worldwide. Health systems are challenged to ensure essential levels of healthcare towards all patients, including those who need routine assistance. CONCLUSION: Performance intelligence plays an essential role as part of a broader public health strategy in guiding the decisions of health system actors on the implementation of contextualised measures to tackle COVID-19 or any future epidemic as well as their effect on the health system at large. This should be based on commonly agreed-upon standardised data and fit-for-purpose indicators, making optimal use of existing health information infrastructures. The HealthPros Network can make a meaningful contribution.

PROMs in post-mastectomy care: Patient self-reports (BREAST-Q™) as a powerful instrument to personalize medical services.

One of the goals of immediate breast reconstruction (IBR) is to satisfy the patient's outcome. Recent studies therefore tended to focus on the patient's perception of the care and on the impact on quality of life using patients-reported-outcome-measures (PROMs), able to measure the health status directly without the clinician's interposition. We present a preliminary prospective study on 333 patients who underwent mastectomy with IBR in a two-year period, in a single Italian centre, using a dedicated PROMs, the BREAST-Q™, to determine the patient's satisfaction. We studied two groups of IBR: Group A (two-step with tissue-expander) and Group B (one-step: prosthesis/mesh) and conducted a pre- and post-operative comparison for each group to evaluate score-gain over time, and a group-score comparison to determine whether differences were significant between reconstruction types. Two-hundred-and-nine were actually enrolled and 132 completed all the questionnaires. The response rate was 62.8% and the compliance rate (completion of all the questionnaires) was 63.1%. In both groups all the analyzed domains worsened comparing the pre and post-operative period; the differences were statistically significant only for physical and sexual-wellbeing. In the comparison between the two groups, none of the detected differences reached the statistical significance. According to our experience, we can state that PROMs could improve the health concept redefining the variables to be monitored even if data is still insufficient to draw any definitive conclusion. PROMs can help surgeons and patients decide the most appropriate surgery for a particular patient-profile and to identify those who require further support.

Carrier priming effect of CRM197 is related to an enhanced B and T cell activation in meningococcal serogroup A conjugate vaccination. Immunological comparison between CRM197 and diphtheria toxoid.

Glycoconjugate vaccines are composed of capsular polysaccharides (CPSs) of a pathogenic bacteria covalently linked to carrier proteins. Pre-exposure to the carrier is known to influence the efficacy of the glycoconjugate, by inducing enhanced or suppressed anti-CPS response. Following our previous work on the immunogenicity of diphtheria toxin mutant CRM197 and formaldehyde-treated diphtheria toxoid (DT) as carriers for meningococcal A (MenA) conjugates in mouse model, we further investigated the role of the carrier on the immunological response to glycoconjugate vaccines. We previously showed that high dosage DT priming could result in carrier-induced epitopic suppression (CIES), an event that did not occur for CRM197 priming, and we observed that anti-DT IgGs could cross-react with DT based conjugates in vitro. Here, we confirmed the cross-reactivity of anti-carrier IgGs with DT conjugates in vivo. Furthermore, we analyzed the splenocytes of animals primed with the carrier and subsequently immunized with the MenA conjugate. Pre-exposure to the carrier protein, both CRM197 and DT, resulted in increased carrier-specific plasma and memory B cell response. However, only for CRM197 priming an enhanced carbohydrate-specific plasma cell response was observed. Analysis of circulating IgGs confirmed these observations. Memory to the CPS resulted to be non-influenced by carrier priming. Analysis of T helper response showed an enhancement effect for CRM197 priming, while DT priming resulted in constrained T cell activation. Stimulation with CRM197, which does not require formaldehyde detoxification, of splenocytes from animal immunized with DT suggested that the formaldehyde treatment used to produce DT might be the cause of limited presentation of the antigen to the T cells. We concluded that the dominant carrier-specific B cell response in case of limited T cell recruitment might explain the previously observed CIES phenomenon in case of DT priming.

Factor validity and reliability of the aberrant behavior checklist-community (ABC-C) in an Indian population with intellectual disability.

BACKGROUND: In this study realised in collaboration with the department of psychology and parapsychology of Andhra University, validation of the Aberrant Behavior Checklist-Community (ABC-C) in Telugu, the official language of Andhra Pradesh, one of India's 28 states, was carried out. METHODS: To assess the factor validity and reliability of this Telugu version, 120 participants with moderate to profound intellectual disability (94 men and 26 women, mean age 25.2, SD 7.1) were rated by the staff of the Lebenshilfe Institution for Mentally Handicapped in Visakhapatnam, Andhra Pradesh, India. Rating data were analysed with a confirmatory factor analysis. The internal consistency was estimated by Cronbach's alpha. To confirm the test-retest reliability, 50 participants were rated twice with an interval of 4 weeks, and 50 were rated by pairs of raters to assess inter-rater reliability. RESULTS: Confirmatory factor analysis revealed that the root mean square error of approximation (RMSEA) was equal to 0.06, the comparative fit index (CFI) was equal to 0.77, and the Tucker Lewis index (TLI) was equal to 0.77, which indicated that the model with five correlated factors had a good fit. Coefficient alpha ranged from 0.85 to 0.92 across the five subscales. Spearman's rank correlation coefficients for inter-rater reliability tests ranged from 0.65 to 0.75, and the correlations for test-retest reliability ranged from 0.58 to 0.76. All reliability coefficients were statistically significant (P < 0.01). CONCLUSION: The factor validity and reliability of Telugu version of the ABC-C evidenced factor validity and reliability comparable to the original English version and appears to be useful for assessing behaviour disorders in Indian people with intellectual disabilities.

Constitutive proteasomal degradation of TWIST-1 in epithelial-ovarian cancer stem cells impacts differentiation and metastatic potential.

Epithelial-mesenchymal transition (EMT) is a critical process for embryogenesis but is abnormally activated during cancer metastasis and recurrence. This process enables epithelial cancer cells to acquire mobility and traits associated with stemness. It is unknown whether epithelial stem cells or epithelial cancer stem cells are able to undergo EMT, and what molecular mechanism regulates this process in these specific cell types. We found that epithelial-ovarian cancer stem cells (EOC stem cells) are the source of metastatic progenitor cells through a differentiation process involving EMT and mesenchymal-epithelial transition (MET). We demonstrate both in vivo and in vitro the differentiation of EOC stem cells into mesenchymal spheroid-forming cells (MSFCs) and their capacity to initiate an active carcinomatosis. Furthermore, we demonstrate that human EOC stem cells injected intraperitoneally in mice are able to form ovarian tumors, suggesting that the EOC stem cells have the ability to 'home' to the ovaries and establish tumors. Most interestingly, we found that TWIST-1 is constitutively degraded in EOC stem cells, and that the acquisition of TWIST-1 requires additional signals that will trigger the differentiation process. These findings are relevant for understanding the differentiation and metastasis process in EOC stem cells.

Relationships between technical efficiency and the quality and costs of health care in Italy.

OBJECTIVE: This paper reports the measurement of technical efficiency of Tuscan Local Health Authorities and its relationship with quality and appropriateness of care. DESIGN: First, a bias-corrected measure of technical efficiency was developed using the bootstrap technique applied to data envelopment analysis. Then, correlation analysis was used to investigate the relationships among technical efficiency, quality and appropriateness of care. SETTING AND PARTICIPANTS: These analyses have been applied to the Local Health Authorities of Tuscany Region (Italy), which provide not only hospital inpatient services, but also prevention and primary care. All top managers of Tuscan Local Health Authorities were involved in selection of the inputs and outputs for calculating technical efficiency. MAIN OUTCOME MEASURES: The main measure used in this study are volume, quality and appropriateness indicators monitored by the multidimensional performance evaluation system developed in the Tuscany Region. RESULTS: On average, Tuscan Local Health Authorities experienced 14(%) of bias-corrected inefficiency in 2007. Correlation analyses showed a significant negative correlation between per capita costs and overall performance. No correlation was found in 2007 between technical efficiency and overall performance or between technical efficiency and per capita costs. CONCLUSIONS: Technical efficiency cannot be considered as an extensive measure of healthcare performance, but evidence shows that Tuscan Local Health Authorities have room for improvement in productivity levels. Indeed, correlation findings suggest that, to pursue financial sustainability, Local Health Authorities mainly have to improve their performance in terms of quality and appropriateness.

Binding of the hepatitis C virus envelope protein E2 to CD81 provides a co-stimulatory signal for human T cells.

Chronic hepatitis C virus (HCV) infection frequently develops into liver disease and is accompanied by extra-hepatic autoimmune manifestations. The tetraspanin CD81 is a putative HCV receptor as it binds the E2 envelope glycoprotein of HCV and bona fide HCV particles. Here we show that HCV E2 binding to CD81 on human cells in vitro lowers the threshold for IL-2 receptor alpha expression and IL-2 production, resulting in strongly increased T cell proliferation. HCV E2-induced co-stimulation also enhances the production of IFN-gamma and IL-4 and causes increased TCR down-regulation. This suggests that binding of HCV particles to CD81 on T cells in vivo may lead to activation by otherwise suboptimal stimuli. Therefore, co-stimulation of autoreactive T cells by HCV may contribute to liver damage and autoimmune phenomena observed in HCV infection.

Thymic hyperplasia and lung carcinomas in a line of mice transgenic for keratin 5-driven HPV16 E6/E7 oncogenes.

Human Papillomavirus type 16 (HPV-16) is the cause of both benign lesions and ano-genital cancers. In HPV-associated cancers the transforming properties of the expressed viral E6 and E7 proteins have been revealed by a number of different assays. We have generated transgenic mice expressing HPV-16 E6/E7 genes under the control of the murine keratin 5 gene promoter, which should confer cell-type specific expression in the basal cells of squamous stratified epithelia. Transgenic mice developed thymic hyperplasia and lung neoplasia with 100% frequency, the thymus showing a size increase at 2 months and reaching the maximum dimension at 6 months, when lung carcinomas appeared. After this time the size of hyperplastic thymi decreased, while malignant formations invaded the mediastinal area. Hepatic metastasis could be also observed in some of the animals at the autopsy and death invariably occurred around 10-11 months of age.

An in vivo model of hyperacute rejection: characterization and evaluation of the effect of transgenic human complement inhibitors.

Hyperacute rejection (HAR) occurring after transplantation within phylogenetically distant species is a severe reaction triggered by preexisting xenoreactive antibodies and complement activation, leading to the destruction of the donor organ. Expression of human complement inhibitors in transgenic pig organs prolongs the survival of xenograft in experimental models. Moreover, the extent of protection from hyperacute rejection is dependent on the level and site of expression of the transgenic molecules and, probably, on the combination of different molecules. In this regard a small animal model to test the efficacy of expression vectors and different human molecules could be very advantageous. A murine model developed in our laboratory was characterized by measurement of several parameters characteristic of HAR in the livers of control and transgenic mice expressing transgenic human DAF (CD55) or MCP (CD46) at the end of 2 h of perfusion with human plasma and after I day. The parameters studied were heamatological values of hepatic functions (GOT and GPT), induction of pro-inflammatory molecules and histopathological evaluation. Cytokines (IL-1alpha, IL-1beta, IL-6) induction and exposure of P-selectin on the endothelial cell surface, was only observed in control animals after 2 h of perfusion, as an early event. GOT and GPT values increase dramatically after 2 h perfusion and 1 day after the treatment according to the histopathological observation of liver damage. On the contrary, the livers of hDAF or hMCP transgenic mice, under the same treatment were significantly protected although the extent of this protection is dependent on the level of expression of transgenic human molecules.

Life, activation and death of intrahepatic lymphocytes in chronic hepatitis C.

The healthy liver of adult humans has little or no lymphocyte component and the histological finding of intrahepatic lymphocytes (IHL) is evidence of liver pathology. In a liver injured by chronic hepatitis C, the most common chronic liver disease, most IHL are activated/pro-inflammatory cells, which are particularly enriched for effectors of innate immunity (natural killer (NK), natural T, and other NK-like T cells). IHL do not undergo clonal expansion in the liver but migrate from extrahepatic sites to the chronically infected liver, where they display effector function and subsequently die, suggesting that maintenance of the IHL pool depends on continuous lymphocyte migration. The cytotoxic and inflammatory functions of these IHL have three potential outcomes: 1) they could be helpful in clearing the virus (a rare case in hepatitis C virus (HCV) infection); 2) they could be useless and have no effect on the infection; or 3) they could be harmful, whereby overaggressive lymphocyte responses destroy the liver in a continuous and unsuccessful attempt to clear the virus. Unfortunately, we do not know as of yet which of these possibilities is the case and, therefore, a more complete picture of the intrahepatic immune response will be relevant to the development of new therapeutic strategies against HCV. Additionally and from a more general perspective, due to the availability of biopsied material and the high prevalence (approximately 3%) of HCV infection worldwide, studying the chronically inflamed liver of hepatitis C patients is an ideal model to investigate the poorly understood processes of lymphocyte trafficking, activation and death to non-lymphoid sites of chronic inflammation in man.

Identification of vaccine candidates against serogroup B meningococcus by whole-genome sequencing.

Neisseria meningitidis is a major cause of bacterial septicemia and meningitis. Sequence variation of surface-exposed proteins and cross-reactivity of the serogroup B capsular polysaccharide with human tissues have hampered efforts to develop a successful vaccine. To overcome these obstacles, the entire genome sequence of a virulent serogroup B strain (MC58) was used to identify vaccine candidates. A total of 350 candidate antigens were expressed in Escherichia coli, purified, and used to immunize mice. The sera allowed the identification of proteins that are surface exposed, that are conserved in sequence across a range of strains, and that induce a bactericidal antibody response, a property known to correlate with vaccine efficacy in humans.

Activation of the human P-glycoprotein ATPase by trypsin.

The human MDR1 gene product, P-glycoprotein (Pgp), a tandemly duplicated molecule containing two putative ATP- and perhaps two drug-binding sites, is responsible for multidrug resistance in tumors. In this report, we characterized the effects of trypsinization of Pgp on its ATPase function. Incubation of Pgp-containing membranes with trypsin at a ratio of 1000:1 (w/w) resulted in a gradual increase in the basal- and the drug-stimulated ATPase activities of Pgp in a time-dependent manner. The maximal basal-, verapamil-, and vinblastine-stimulated ATPase activities of the trypsinized Pgp were approximately 1.8-, 1.5-, and 1.75-fold higher than the activities of the native Pgp, respectively. Increased basal- and drug-stimulated ATPase activities of the Pgp were also observed when the ratio of membrane protein to trypsin in the incubation mixtures was raised to 10:1 (w/w). Immunoblotting analysis of Pgp tryptic digests using Pgp-specific NH(2)11, C219, and C494 antibodies together revealed the degradation of full-length Pgp and formation of at least eight peptides migrating in the 36-60 kDa range. Immunoprecipitation reactions using NH(2)11 and C494 antibodies have suggested that the peptides originating from the NH(2) half of Pgp are in strong association with the COOH half of the peptide. These findings suggest that while Pgp fragments together exhibit the ATPase functional characteristics, Pgp possesses a cleavage activation site or region, and its cleavage leads to the activation of basal ATPase function of Pgp.

[T-cell interferon-gamma, tumor necrosis factor-alpha and interleukin-6 receptor binding in patients with multiple sclerosis. Effects of interferon-beta-1b treatment]. / Las uniones a los receptores para el interferón-gamma, el factor de necrosis tumoral-alpha y la interleucina-6 en linfocitos T de pacientes con esclerosis múltiple. Resultado del tratamiento con interferón-beta 1b.

INTRODUCTION: Multiple sclerosis (MS) is a T-cell-mediated demyelinating disease of the central nervous system (CNS), in which the cytokine network may be deranged. Interferon (IFN)-gamma, interleukin (IL)-6, and tumor necrosis factor (TNF)-alpha are cytokines with several effects on the neuroimmune system. Specific IFN-gamma, IL-6, and TNF-alpha receptors have been found on human lymphocytes and other cell types. PATIENTS AND METHODS: We assayed IFN-gamma, TNF-alpha, and IL-6 binding on peripheral blood T cells from MS patients, as compared with healthy subjects. T cells from MS patients have significantly less IFN-gamma receptors, and more TNF-alpha and IL-6 receptors than those from controls. Such receptors are of the same type in patients and healthy subjects. By comparing MS patients' subgroups with each other, significant differences in mean Bmax values have been found between patients in a stable phase and those in relapse, and between stable patients and those in an evolutive phase. As far as IL-6 binding is concerned, significant differences in mean Bmax values were observed only between patients in stable phase and those in relapse. RESULTS: T lymphocytes from untreated MS patients, which had significantly smaller amounts of IFN-gamma receptors than those from controls, and more TNF-alpha and IL-6 receptors than controls showed a significant increase in IFN-gamma binding, and a significant decrease in TNF-alpha and IL-6 binding after a 3-month IFN-beta 1b treatment. T-cell IFN-gamma Bmax values were even higher, and those of TNF-alpha and IL-6 were lower after 6 months. CONCLUSION: We discuss these results in terms of MS immunopathophysiology, since activated T cells have decreased IFN-gamma, and increased TNF-alpha and IL-6 receptor amounts.

Dynamics of intra-hepatic lymphocytes in chronic hepatitis C: enrichment for Valpha24+ T cells and rapid elimination of effector cells by apoptosis.

Chronic viral hepatitis is characterized by a dramatic lymphocyte infiltrate in the liver. Although it is one of the most common chronic inflammatory diseases in humans, little information is available on the functional state of these intra-hepatic lymphocytes (IHL). To address this issue, we have optimized cytofluorimetric techniques to assess directly ex vivo the functions, dynamics and repertoires of IHL isolated from biopsies of patients with chronic hepatitis C. We estimate that 1% of the total body lymphocytes infiltrate the inflamed liver and find that, at variance with peripheral blood lymphocytes (PBL) isolated from the same patients, most IHL display an activated phenotype and produce Th1 type lymphokines when stimulated in vitro. Virtually all IHL are found in the G0/G1 state of the cell cycle, while a sizeable percentage of them is undergoing programmed cell death in vivo, as detected by the TUNEL assay performed on freshly isolated cells. In contrast again to PBL from the same patients, IHL show a preferential compartmentalization of NK and TCRgamma/delta+ cells, and a remarkable (up to 20-fold) enrichment for Valpha24+ T cells. Together our data suggest that in a liver injured by chronic hepatitis C, most IHL are pro-inflammatory activated cells which are highly enriched for effectors of innate resistance. These IHL do not undergo clonal expansion in the liver but rather display effector function and die in situ at a high rate, suggesting that maintenance of the IHL pool is dependent on continuous migration from extra-hepatic sites.

Binding of the Helicobacter pylori vacuolating cytotoxin to target cells.

The vacuolating cytotoxin of Helicobacter pylori, VacA, enters the cytoplasm of target cells and causes vacuolar degeneration by interfering with late stages of endocytosis. By using indirect immunofluorescence and flow cytometry, we have demonstrated that VacA binds to specific high-affinity cell surface receptors and that this interaction is necessary for cell intoxication.

CD4+/CD45RA+ 'naive' T cells and immunological response to influenza virus vaccine in B-cell chronic lymphocytic leukaemia patients.

B-cell chronic lymphocytic leukaemia (B-CLL) is characterized by a high frequency of infections, including those of viral aetiology. Previous reports have demonstrated a specific immunologic response to influenza virus vaccine in B-CLL patients with normal IgG levels. In this study, we have evaluated different immunophenotypically defined B and T cell subsets in 18 B-CLL patients before immunization with killed-influenza-virus vaccine. A correlation between immunological response to vaccination and both absolute numbers of CD4+/CD45RA+ naive T cells and CD5- B cells was found. These data may suggest a supporting role of the CD4+/CD45RA+ T cell subset in the specific antibody response to vaccination with influenza virus vaccine in B-CLL patients.

Detoxification of the Helicobacter pylori cytotoxin.

Treatment of the Helicobacter pylori vacuolating cytotoxin with very low concentrations of formaldehyde resulted in abrogation of toxic activity in both a HeLa cell vacuolation assay and an in vivo assay of gastric epithelial damage. Detoxification had only a minimal effect on the integrity of the oligomeric or monomeric structure. The toxoid retained the ability to bind to target cells and to induce high-titer neutralizing antibodies after immunization of rabbits. Furthermore, oral immunization of mice with the toxoid resulted in protection against infective challenge with mouse-adapted strains of H. pylori. The sensitivity of the toxin to formaldehyde treatment suggests that a few lysine residues in the protein may be essential for toxic activity and that VacA detoxified in this manner may be a potential candidate for inclusion in a vaccine against H. pylori infection and disease.

Induction of CD4+ T cell depletion in mice doubly transgenic for HIV gp120 and human CD4.

It has been suggested that loss of uninfected T cells in HIV infection occurs because of lymphocyte activation resulting in cell death by apoptosis. To address the question of whether cross-linking of CD4/HIV gp120 complexes by antibodies were sufficient to induce T cell depletion in vivo, we developed an animal model of continuous interaction between human CD4 (hCD4), gp120 and anti-gp120 antibodies in the absence of other viral factors. Double-transgenic mice have been generated in which T cells express on their membrane hCD4 and secrete HIV gp120. Although these mice have hCD4/gp120 complexes present on the surface of T cells, they do not show gross immunological abnormalities, and they are able to produce anti-gp120 antibodies following immunization with denaturated gp120. However, double-transgenic mice with antibodies to gp120, when immunized with tetanus toxoid, mount an IgG response that is significantly lower than that of double-transgenic mice without antibodies to gp120. Furthermore, the presence of anti-gp120 antibodies leads to CD4+ T cell depletion and immunodeficiency in the absence of HIV infection. Thus, the antibody response to gp120 can lead to CD4+ T cell attrition in vivo.