In Italy, a nationwide population-based colorectal cancer (CRC) screening initiative has been in place since 2006. In recent years, there has been a growing interest in involving community pharmacies ...in this activity. This commentary provides an insightful analysis of the integration between the screening program of the Local Health Authority (LHA) of Bologna (Northern Italy) and community pharmacies. A horizontal integration at the micro level with service and clinical integrations supported by meso-level policy (regional authority) was applied. Four types of integration such as normative, informational, financial and functional serving as enablers were implemented. A high level of depth of consensus, connectivity, communication, and trust was pursued. The program achieved large participation from community pharmacies, with 91.1% (n = 234) of pharmacies in the LHA territory actively participating. On average, each pharmacy served 1,228 (range, 1,021-1,519) target citizens. Between 2021 (the first full year under the community pharmacy model) and 2022, pharmacies delivered an annual mean of 68,295 kits (range, 12-840). In 2021, there was a remarkably high level of screening completion, with 93.7% of fecal immunochemical tests being returned to pharmacies. This percentage increased by 3.3% in 2022. In our setting, pharmacy involvement improved service quality by introducing complete traceability of kits and specimen flow, as well as temperature control. It also led to a 4.6% increase in attendance rates compared to the previous organizational model (61.6% vs. 57%; P < 0.001). Finally, additional European experiences involving community pharmacies in organized CRC screening programs, resembling the Bologna setting, are reported.
: Obesity is a pandemic disease characterized by excessive severe body comorbidities. Reduction in fat accumulation represents a mechanism of prevention, and the replacement of white adipose tissue ...(WAT) with brown adipose tissue (BAT) has been proposed as one promising strategy against obesity. In the present study, we sought to investigate the ability of a natural mixture of polyphenols and micronutrients (A5
) to counteract white adipogenesis by promoting WAT browning.
: For this study, we employed a murine 3T3-L1 fibroblast cell line treated with A5
, or DMSO as control, during the differentiation in mature adipocytes for 10 days. Cell cycle analysis was performed using propidium iodide staining and cytofluorimetric analysis. Intracellular lipid contents were detected by Oil Red O staining. Inflammation Array, along with qRT-PCR and Western Blot analyses, served to measure the expression of the analyzed markers, such as pro-inflammatory cytokines.
: A5
administration significantly reduced lipids' accumulation in adipocytes when compared to control cells (
< 0.005). Similarly, A5
inhibited cellular proliferation during the mitotic clonal expansion (MCE), the most relevant stage in adipocytes differentiation (
< 0.0001). We also found that A5
significantly reduced the release of pro-inflammatory cytokines, such as IL-6 and Leptin (
< 0.005), and promoted fat browning and fatty acid oxidation through increasing expression levels of genes related to BAT, such as UCP1 (
< 0.05). This thermogenic process is mediated via AMPK-ATGL pathway activation.
: Overall, these results demonstrated that the synergistic effect of compounds contained in A5
may be able to counteract adipogenesis and then obesity by inducing fat browning.
An immune function assay shows promise for identifying solid organ recipients at risk for infection or rejection. The following randomized prospective study was designed to assess the clinical ...benefits of adjusting immunosuppressive therapy in liver recipients based on immune function assay results.
Adult liver recipients were randomized to standard practice (control group; n = 102) or serial immune function testing (interventional group; n = 100) performed with a commercially available in vitro diagnostic assay (ImmuKnow; Viracor-IBT Laboratories, Lee's Summit, MO) before transplantation, immediately after surgery and at day 1, weeks 1 to 4, 6, and 8, and months 3 to 6, 9, and 12. The assay was repeated within 7 days of suspected/confirmed rejection/infection and within 1 week after event resolution.
Based on immune function values, tacrolimus doses were reduced 25% when values were less than 130 ng/mL adenosine triphosphate (low immune cell response) and increased 25% when values were greater than 450 ng/mL adenosine triphosphate (strong immune cell response). The 1-year patient survival was significantly higher in the interventional arm (95% vs 82%; P < 0.01) and the incidence of infections longer than 14 days after transplantation was significantly lower among patients in the interventional arm (42.0% vs. 54.9%, P < 0.05). The difference in infection rates was because of lower bacterial (32% vs 46%; P < 0.05) and fungal infection (2% vs 11%; P < 0.05). Among recipients without adverse events, the study group had lower tacrolimus dosages and blood levels.
Immune function testing provided additional data which helped optimize immunosuppression and improve patient outcomes.
Transformation from chronic (CP) to blast phase (BP) in myeloproliferative neoplasm (MPN) remains poorly characterized, and no specific mutation pattern has been highlighted. BP-MPN represents an ...unmet need, due to its refractoriness to treatment and dismal outcome. Taking advantage of the granularity provided by single-cell sequencing (SCS), we analyzed paired samples of CP and BP in 10 patients to map clonal trajectories and interrogate target copy number variants (CNVs). Already at diagnosis, MPN present as oligoclonal diseases with varying ratio of mutated and wild-type cells, including cases where normal hematopoiesis was entirely surmised by mutated clones. BP originated from increasing clonal complexity, either on top or independent of a driver mutation, through acquisition of novel mutations as well as accumulation of clones harboring multiple mutations, that were detected at CP by SCS but were missed by bulk sequencing. There were progressive copy-number imbalances from CP to BP, that configured distinct clonal profiles and identified recurrences in genes including NF1, TET2, and BCOR, suggesting an additional level of complexity and contribution to leukemic transformation. EZH2 emerged as the gene most frequently affected by single nucleotide and CNVs, that might result in EZH2/PRC2-mediated transcriptional deregulation, as supported by combined scATAC-seq and snRNA-seq analysis of the leukemic clone in a representative case. Overall, findings provided insights into the pathogenesis of MPN-BP, identified CNVs as a hitherto poorly characterized mechanism and point to EZH2 dysregulation as target. Serial assessment of clonal dynamics might potentially allow early detection of impending disease transformation, with therapeutic implications.
Few data on the diagnostic performance of serological tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are currently available. We evaluated sensitivity and ...specificity of five different widely used commercial serological assays for the detection of SARS-CoV-2-specific IgG, IgM, and IgA antibodies using reverse transcriptase-PCR assay in nasopharyngeal swab as reference standard test.
A total of 337 plasma samples collected in the period April-June 2020 from SARS-CoV-2 RT-PCR positive (
= 207) and negative (
= 130) subjects were investigated by one point-of-care lateral flow immunochromatographic assay (LFIA IgG and IgM, Technogenetics) and four fully automated assays: two chemiluminescence immunoassays (CLIA-iFlash IgG and IgM, Shenzhen YHLO Biotech and CLIA-LIAISON
XL IgG, DiaSorin), one electrochemiluminescence immunoassay (ECLIA-Elecsys
total predominant IgG, Roche), and one enzyme-linked immunosorbent assay (ELISA IgA, Euroimmune).
The overall sensitivity of all IgG serological assays was >80% and the specificity was >97%. The sensitivity of IgG assays was lower within 2 weeks from the onset of symptoms ranging from 70.8 to 80%. The LFIA and CLIA-iFlash IgM showed an overall low sensitivity of 47.6 and 54.6%, while the specificity was 98.5 and 96.2%, respectively. The ELISA IgA yielded a sensitivity of 84.3% and specificity of 81.7%. However, the ELISA IgA result was indeterminate in 11.7% of cases.
IgG serological assays seem to be a reliable tool for the retrospective diagnosis of SARS-CoV-2 infection. IgM assays seem to have a low sensitivity and IgA assay is limited by a substantial rate of indeterminate results.
Hearing Loss (HL) is the most common sensory disorder in humans, and more than half ofcases are due to genetic factors. In 30% of cases, hereditary HL is associated withadditional clinical features, ...and it is defined syndromic (SHL), whereas in 70% of cases HLis the only symptom, and it is considered nonsyndromic (NSHL). HL is characterised by anextreme genetic heterogeneity, with more than 150 loci currently associated and at least 100genes identified, making extremely challenging to obtain a molecular diagnosis withtraditional screening methods. For these reasons, whole-exome sequencing (WES) hasbeen introduced to search for mutations and novel genes underlying the disease.In this frame, this thesis describes the study of the genetic bases of deafness in 11 HL (3SHL and 8 NSHL) families applying WES and an accurate functional validation of thecandidate mutations.This approach allowed the identification of the causative mutations in 7 out of the 11families analysed, while for 3 NSHL families no strong candidate pathogenic variantsemerged from our WES data analyses.In addition, in one NSHL family we identified a missense variant in the candidate deafnesscausinggene DIAPH2, coding for a protein involved in actin filament elongation. My invitrostudies indicate a possible functional impairment of the mutant DIAPH2 protein,which might be very relevant in hearing function. In fact, immunohistochemical studiesindicate that the mouse ortholog protein Diap2 is expressed in the cochlea in the actin-richstereocilia of the sensory outer hair cells during development. Auditory brainstem responsemeasurements to evaluate the hearing phenotype of Diaph2 knock-out and knock-in micewere also undertaken. However, at least at the time points analysed, no hearing impairmentwas detected in the mouse models. Consequently, the role of DIAPH2 in HL in humansstill needs to be further clarified.
We tested whether a didactic and a narrative video (i.e. educational content and personal stories versus irrelevant information) could boost colorectal cancer (CRC) screening intention directly and ...through cognitive predictors of CRC screening behavior. We also tested whether exposure to a story changed participants' affective forecasting, reducing the perception of negative emotions associated with CRC screening (disgust, embarrassment, and fear). The study was conducted online with a between‐participants design and recruiting a convenience sample (N = 375). We found that, compared with watching the control video, being exposed to the narrative video about CRC screening was indirectly associated with greater screening intention via vicarious experience and positive attitudes, whereas watching the didactic video was positively associated with CRC screening intention only among participants who had received an invitation letter but did not get screened, and among those yet to receive an invitation to screen. In the latter group, screening intention was boosted through positive attitudes. Our findings do not confirm that stories change affective forecasting, but narration likely fosters messages acceptance through vicarious experience. We also found support for the effectiveness of physicians' recommendations in promoting CRC screening, an intervention that might be effectively administered through a generalized, cost‐effective video.
We performed serological and molecular pretransplant screening in solid organ transplant (SOT) donors and recipients in north central Italy and a surveillance program for human herpesvirus 8 (HHV8) ...infection after transplant, aiming to establish an optimal management of HHV8 infection in SOT recipients.
For pretransplant HHV8 screening in both donors and recipients, 6 serological (4 indirect immunofluorescent assays IFA and 2 enzyme-linked immunosorbent assays-both HHV8 lytic and latent antigen based) and 2 molecular assays were used. A reference standard to identify HHV8-positive patients was defined by at least 2 positive assays. All transplant patients at risk to develop HHV8-related disease underwent virological posttransplant monitoring by quantitative real-time polymerase chain reaction (PCR) assay.
Human herpesvirus 8 seroprevalence was 4% (10/249) in donors and 18% (93/517) in organ recipients. The best performance was obtained by 2 lytic antigen-based IFAs that showed almost perfect agreement to the reference standard (0.943 and 0.931 Cohen kappa). Human herpesvirus 8-DNA was detected in 6.8% and 2.9% of HHV8-seropositive donor samples by in-house nested PCR and quantitative real-time PCR assays, respectively. After transplant, 3 (25%) of 12 HHV8-mismatch patients (seropositive donor/seronegative recipient) developed a primary infection, one of whom developed a lethal nonmalignant illness. Two of 93 HHV8-seropositive recipients (2.1%) had viral replication in posttransplant period, one of whom developed Kaposi sarcoma.
Serological assays, specifically lytic IFAs, were the best methodological approach to identify HHV8-infected SOT donors and recipients. A very low incidence (1.9%) of posttransplant HHV8-related disease was observed.
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