Obesity and overweight represent a growing health problem worldwide. Genes regulating the intake and metabolism of different nutrients can positively or negatively influence the efficacy of ...nutritional interventions against obesity and its complications. The aim of this study was to assess changes in anthropometric and clinical parameters and the adherence to a Mediterranean diet (MedDiet) over time in relation to nutrigenetic variants in overweight or obese subjects affected by Type 2 Diabetes (T2D) or dysglycemia, who were included in a nutritional program. A total of 23 subjects were included in this study. Clinical parameters, physical activity levels, and the adherence to a MedDiet were evaluated at baseline, at 6 (T6), and at 12 months (T12) during and after a diet/lifestyle intervention. In a single blood sample from each subject, rs1984112 (A>G) and rs1761667 (G>A) in CD36; rs7950226 (G>A) in BMAL1; and rs1801260 (A>G), rs4864548 (A>G), and rs3736544 (G>A) in CLOCK were genotyped with Real-Time PCR. Significant associations were observed between CD36 rs1761667 and weight (p = 0.025), hip circumference (p = 0.042), triglycerides (p = 0.047), and HbA1c (p = 0.012) at baseline. Moreover, the genotype AA in CD36 rs1761667 was significantly associated with a lower BMI when compared to G carriers at baseline, at T6, and also at T12. In addition, subjects with the AA genotype at CD36 rs1984112 had significantly lower levels of HbA1c (p = 0.027) than the GG and AG genotypes at baseline. These results show that variants in CD36 can have an impact on anthropometric and clinical parameters in overweight or obese subjects affected by T2D or dysglycemia, and that it might influence the success of the diet/lifestyle intervention.
Obesity and overweight are common and complex conditions influenced by multiple genetic and environmental factors. Several genetic variants located in the genes involved in clock systems and fat ...taste perception can affect metabolic health. In particular, the polymorphisms in
and
genes were reported to be significantly related to cardiovascular disease, metabolic syndrome, sleep reduction, and evening preference. Moreover, genetic variants in the
gene have been shown to be involved in lipid metabolism, regulation of fat intake, and body weight regulation. The aim of this study is to evaluate, for the first time, the association between variants in some candidate genes (namely,
rs7950226 (
>
),
rs1801260 (
>
),
rs4864548 (
>
),
rs3736544 (
>
),
rs1984112 (
>
),
rs1761667 (
>
)) and overweight/obesity (OB) in pregnant women. A total of 163 normal-weight (NW) and 128 OB participants were included. A significant correlation was observed between
-allele in
rs4864548 and an increased risk of obesity (OR: 1.97; 95% CI 1.22-3.10,
= 0.005). In addition, we found that subjects carrying the haplotype of rs1801260-
, rs4864548-
, and rs3736544-
are likely to be overweight or obese (OR 1.47, 95% CI 1.03-2.09,
= 0.030), compared with those with other haplotypes. Moreover, a significant relation was observed between third-trimester lipid parameters and genetic variants-namely,
rs1984112,
rs1761667,
rs7950226, and
rs1801260. A multivariate logistic regression model revealed that
rs4864548
-allele carriage was a strong risk factor for obesity (OR 2.05, 95% CI 1.07-3.93,
= 0.029); on the other hand, greater adherence to Mediterranean diet (OR 0.80, 95% CI 0.65-0.98,
= 0.038) and higher HDL levels (OR 0.96, 95% CI 0.94-0.99,
= 0.021) were related to a reduced risk of obesity. Interestingly, an association between maternal
rs4864548 and neonatal birthweight was detected (
= 0.025). These data suggest a potential role of the polymorphisms in clock systems and in fat taste perception in both susceptibility to overweight/obesity and influencing the related metabolic traits in pregnant women.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Interactions of malignant multiple myeloma (MM) plasma cells (MM-cells) with the microenvironment control MM-cell growth, survival, drug-resistance and dissemination. As in MM microvascular density ...increases in the bone marrow (BM), we investigated whether BM MM endothelial cells (MMECs) control disease progression via the junctional adhesion molecule A (JAM-A). Membrane and cytoplasmic JAM-A levels were upregulated in MMECs in 111 newly diagnosed (NDMM) and 201 relapsed-refractory (RRMM) patients compared to monoclonal gammopathy of undetermined significance (MGUS) and healthy controls. Elevated membrane expression of JAM-A on MMECs predicted poor clinical outcome. Mechanistically, addition of recombinant JAM-A to MMECs increased angiogenesis whereas its inhibition impaired angiogenesis and MM growth in 2D and 3D in vitro cell culture and chorioallantoic membrane-assays. To corroborate these findings, we treated MM bearing mice with JAM-A blocking mAb and demonstrated impaired MM progression corresponding to decreased MM-related vascularity. These findings support JAM-A as an important mediator of MM progression through facilitating MM-associated angiogenesis. Collectively, elevated JAM-A expression on bone marrow endothelial cells is an independent prognostic factor for patient survival in both NDMM and RRMM. Blocking JAM-A restricts angiogenesis in vitro, in embrio and in vivo and represents a suitable druggable molecule to halt neoangiogenesis and MM progression.
To minimize the toxicity and impact of combined antiretroviral therapy (cART) on the lifestyle of people living with Human Immunodeficiency Virus (PLWH), scientific community evaluated the efficacy, ...safety and sustained virologic response of two drugs antiretroviral regimens, in particular dolutegravir (DTG). The effects of deintensification therapy on inflammatory settings are currently unknown in PLWH. Thus, our study explored the inflammatory state in virologically suppressed HIV individuals between patients in treatment with a DTG-containing dual therapy (2DR) versus triple regimen therapies (3DR). We enrolled a total of 116 subjects in 2DRs or 3DRs regimens, and the plasma levels of pro- and anti-inflammatory cytokines (in particular IL-1beta, IL-10, IL-18, IL-33, IL-36 and IFN-gamma) have been evaluated. CD4 + cell's median value was 729.0 cell/microL in the 3DR group and 771.5 cell/microL in 2DR group; the viral load was negative in all patients. Significant differences were found in levels of IL-18 (648.8 cell/microL in 3DR group vs. 475.0 cell/microL in 2DR group, p = 0.034) and IL-36 (281.7 cell/microL in 3DR group vs. 247.0 cell/microL in 2DR group, p = 0.050), and a correlation between IL-18 and IL-36 was found in 3DR group (rho = 0.266, p = 0.015). This single-center retrospective pharmacological study confirms the absence of significant differences in IL-1beta, IL-10, IL-33, and IFN-gamma levels between patients on two-drug antiretroviral regimens compared to patients on 3DR antiretroviral regimens. Patients in 2DR show greater control over IL-18 and IL-36 serum levels, cytokines related to an increased cardiovascular risk and development of age-related chronic diseases. Based on our results, we suggest that DTG-based 2DR antiretroviral regimens could be associated with better control of the chronic inflammation that characterizes the population living with HIV in effective ART.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Human chorionic gonadotropin (hCG) is produced by trophoblast cells throughout pregnancy, and gene expression studies have indicated that hCG-beta subunit (hCGβ) expression is active at the 2 ...blastomere stage. Here, we investigated the qualitative hCG output of developing embryos in culture and hCG isoforms expressed in the secretome as a novel sensitive method for detecting hCG. Culture media was collected from the culture plates of 118 embryos in culture (including controls and embryos at different stages of culture) from 16 patients undergoing routine fertility treatment. The hCGβ was detectable in media from 2 pronuclear (2PN) stage embryos through to the blastocyst stage. The hCGβ was absent in 1PN and arrested embryos as well as all media controls. Prior to hatching, hyperglycosylated hCG (hCGh) was observed selectively in 3PN embryos, but after hatching, along with hCG, became the dominant hCG molecule observed. We have reported at the 2PN stage the earliest evidence of hCGβ expression in embryos. There is a suggestion this may be indicative of quality in early embryos, and hCGh seen at the pronuclear stage may suggest triploid abnormality. The dominance of hCG, and hCGh expression, seen after blastocyst hatching may be indicative of potential implantation success. Thus, hCG isoforms have potential roles as biomarkers of embryo viability for embryo/blastocyst transfer.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Predictors of survival and progression of disease in atypical meningiomas are less well documented in the literature compared to benign meningiomas. Higher grade meningiomas tend to recur often and ...one of the most critical aspects is how to best deal with relapses.
A total of 77 consecutive patients who underwent craniotomy for atypical meningioma between 1990-2010 at Oslo University Hospital (OUH) were reviewed.
Median age at surgery was 62.21 interquartile range (IQR): 22.87 years. Fifty-one patients (66.2%) had neurological deficits at presentation. Fifty-four patients (70.1%) underwent gross total resection (GTR). Thirty-nine patients (50.7%) had improved/stable neurological outcomes at 6-12 months. Twenty-two patients (28.6%) underwent retreatment, of whom 20 (26.0%) were subjected to resection followed by adjuvant radiotherapy. Overall survival (OS) was significantly longer in patients <65 years (
< 0.001), with preoperative Karnofsky performance scale (KPS) score of ≥ 70 (
= 0.006), and who required no retreatment (
= 0.033). GTR significantly prolonged the retreatment-free survival rate (
< 0.001). STR carried almost a six-fold greater risk of neurological outcome deterioration (
= 0.044).
GTR significantly prolonged retreatment-free survival but had no significant impact on OS. STR was a significant risk factor for deteriorated neurological outcome. Age, preoperative KPS, and retreatment were all strong predictors of OS. Median time-to-retreatment (TTR) did not shorten significantly throughout repeated surgeries.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The evidence shows a reduction in pediatric emergency department (PED) flows during the early stages of the COVID-19 pandemic. Using interrupted time-series analysis, we evaluated the impact of ...different stages of the pandemic response on overall and cause-specific PED attendance at a tertiary hospital in south Italy. Our methods included evaluations of total visits, hospitalizations, accesses for critical illnesses and four etiological categories (transmissible and non-transmissible infectious diseases, trauma and mental-health) during March-December 2020, which were compared with analogous intervals from 2016 to 2019; the pandemic period was divided into three segments: the "first lockdown" (FL, 9 March-3 May), the "post-lockdown" (PL, 4 May-6 November) and the "second lockdown" (SL, 7 November-31 December). Our results showed that attendance dropped by a mean of 50.09% during the pandemic stages, while hospitalizations increased. Critical illnesses decreased during FL (incidence rate ratio -IRR- 0.37, 95% CI 0.13, 0.88) e SL (IRR 0.09, 95% CI 0.01, 0.74) and transmissible disease related visits reduced more markedly and persistently (FL: IRR 0.18, 95% CI 0.14, 0.24; PL: IRR 0.20, 95% CI 0.13, 0.31, SL: IRR 0.17, 95% CI 0.10, 0.29). Non-infectious diseases returned to pre-COVID-19 pandemic levels by PL. We concluded that that the results highlight the specific effect of the late 2020 containment measures on transmissible infectious diseases and their burden on pediatric emergency resources. This evidence can inform resource allocation and interventions to mitigate the impact of infectious diseases on pediatric populations and the health-care system.
OBJECTIVE The objective of this study was to analyze the incidence of the primary complications related to positioning or surgery and their impact on neurological outcome in a consecutive series of ...patients undergoing elective surgery in the semisitting position. METHODS The authors prospectively collected and retrospectively analyzed data from adult patients undergoing elective surgery in the semisitting position for a cranial disease. Patients were managed perioperatively according to a standard institutional protocol, a standardized stepwise positioning, and surgical maneuvers to decrease the risk of venous air embolism (VAE) and other complications. Intraoperative and postoperative complications were recorded. Neurointensive care unit (NICU) length of stay (LOS) and hospital LOS were the intermediate endpoints. Neurological outcome was the primary endpoint as determined by the modified Rankin scale (mRS) score at 6 months after surgery. RESULTS Four hundred twenty-five patients were included in the analysis. VAE occurred in 90 cases (21%) and it made no significant statistical difference in NICU LOS, hospital LOS, and neurological outcome. No complication was directly related to the semisitting position, although 46 patients (11%) experienced at least 1 surgery-related complication and NICU LOS and hospital LOS were significantly prolonged in this group. Neurological outcome was significantly worse for patients with complications (p < 0.0001). CONCLUSIONS Even in the presence of intraoperative VAE, the semisitting position was not related to an increased risk of postoperative deficits and can represent a safe additional option for the benefit of specific surgical and patient needs.
Although gross total resection (GTR) is the goal in meningioma surgery, this can sometimes be difficult to achieve in skull base meningiomas. We analyzed clinical outcomes and predictors of survival ...for subtotally resected benign meningiomas.
A total of 212 consecutive patients who underwent subtotal resection (STR) for benign skull base meningioma between 1990-2010 were investigated.
Median age was 57.7 IQR 18.8 years, median preoperative Karnofsky performance status (KPS) was 80.0 IQR 20.0, 75 patients (35.4%) had posterior fossa meningioma. After a median follow-up of 6.2 IQR 7.9 years, retreatment (either radiotherapy or repeated surgery) rate was 16% at 1-year, 27% at 3-years, 34% at 5-years, and 38% at 10-years. Ten patients (4.7%) died perioperatively, 9 (3.5%) had postoperative hematomas, and 2 (0.8%) had postoperative infections. Neurological outcome at final visit was improved/stable in 122 patients (70%). Multivariable analysis identified advanced age and preoperative KPS < 70 as negative predictors for overall survival (OS). Patients who underwent retreatment had no significant reduction of OS.
Advanced age and preoperative KPS were independent predictors of OS. Retreatments did not prolong nor shorten the OS. Clinical outcomes in STR skull base meningiomas were generally worse compared to cohorts with high rates of GTR.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Objectives: Below we report our experience in the use of molnupiravir, the first antiviral drug against SARS-CoV-2 available to us, in the treatment of patients with COVID-19. Materials and Methods: ...We enrolled patients diagnosed with COVID-19 and comorbidities who were candidates for antiviral drug therapy. All patients received molnupiravir (800 mg twice daily). Blood chemistry checks were carried out at T0 and after 7/10 days after starting therapy (T1). Results: There were enrolled within the cohort 100 patients. There was 100.0% compliance with the antiviral treatment. No patient required hospitalization due to worsening of respiratory function or the appearance of serious side effects. The median downtime of viral load was ten days (IQR 8.0–13.0), regardless of the type of vaccination received. The patients who had a shorter distance from vaccination more frequently presented vomiting/diarrhea. During baseline and T1 we found significant differences in the median serum concentrations of the main parameters, in particular of platelets, RDW CV, neutrophils and lymphocytes, the eGFR, liver enzymes, as well as of the main inflammatory markers, CRP and Ferritin. Conclusion: Participants treated with molnupiravir, albeit in risk categories, demonstrated early clinical improvement, no need for hospitalization, and a low rate of adverse events.
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