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Abstract There are currently no standardized therapies for Parkinson disease (PD). Curcumin shows anti-amyloidogenic properties in vitro and may be a promising treatment for PD. We evaluated the effects of curcumin supplementation on clinical scales and misfolded, phosphorylated α-synuclein (p-syn) accumulation in skin biopsies in 19 PD patients who received curcumin supplementation for 12 months and 14 PD patients to treated with curcumin. The patients underwent autonomic (COMPASS-31), motor (MDS-UPDRS and H&Y) and nonmotor (NMSS) questionnaires and skin biopsies to evaluate clinical involvement and p-syn load in skin nerves at the beginning and the end of study. Curcumin and curcuminoid levels were assayed in plasma and CSF. Supplemented patients showed detectable CSF curcuminoid levels that were lower than those in plasma. They showed a decrease of COMPASS-31 and NMSS scores, and a slight p-syn load decrease versus untreated patients who displayed a worsening of these parameters despite increased levodopa doses. Multiple regression models showed a significant effect of curcumin supplementation in decreasing the worsening of the clinical parameters and p-syn load at after curcumin treatment. These data suggest that curcumin can cross the blood-brain barrier, that it is effective in ameliorating clinical parameters and that it shows a tendency to decrease skin p-syn accumulation in PD patients.

Among patients with peripheral arterial disease (PAD) the risk of mortality remains extremely high. We investigated whether arterial stiffness evaluated by aortic Pulse Wave Velocity (aPWV) and Augmentation index normalized for a standard heart rate of 75 bpm (Aix@75), predict cardiovascular disease (CVD) and total mortality in PAD and No-PAD patients. In 231 PAD patients (ankle-brachial index-ABI ≤ 0.9) and 167 No-PAD (ABI ≥ 0.91 < 1.3) the aPWV and Aix @75HR were evaluated using arterial tonometry and ABI values were obtained using an 8-MHz Doppler probe. The CVD and total mortality rates in relation to aPWV and Aix@75HR were analyzed using Cox regression model. During a mean follow-up of 5.4 ± 2 years 39 (16.9%) deaths occurred in PAD patients and 8 (4.8%) in No-PAD. In the population study, the age was a predictor of CVD mortality (HR = 0.143, 95% CI, 0.06–0.23; p = 0.0004) while the aPWV, was a predictor of total mortality (HR = 1.18, 95% CI, 1.07–1.30; p = 0.0008). In the PAD group, the aPWV remained associated with an increased risk for total mortality (HR = 1.14, 95% CI, 1.03–1.27; p = 0.010). An increase of aPWV may be an indicator of total mortality in PAD patients.

Recent studies have indicated that microplastics (MPs) may accumulate in the human body, potentially posing health risks. This preliminary study aimed to investigate the effect of a food supplement (FS: 0.8 g of chitosan derived from Procambarus clarkii, PCC) on the fecal excretion of MPs (20–500 µm size) following ingestion of a standardized meal (SM). Ten healthy volunteers (non-smokers, non-drinkers, non-drug users) participated in a two-phase, crossover design conducted one week apart. In both phases, participants consumed an SM after overnight fasting, and fecal samples were collected the following morning (7–10 am). Phase 1 served as baseline (no PCC), while in Phase 2, PCC was administered immediately before the SM. Sixteen types of MPs were analyzed. A modest increase (5%) in fecal mass was observed after PCC intake. MP counts were 356 in the SM, 656 ± 110 in Phase 1 feces, and 965 ± 165 in Phase 2 feces. The excretion of nine MPs—PA, PAN, PAM, PE, PES, PET, PP, PS, and RA—was enhanced by PCC. These preliminary findings suggest that PCC promotes the fecal elimination of MPs. Further controlled studies are needed to validate these results and assess their potential relevance for dietary interventions.

Background Levothyroxine (LT 4 ) treatment can lead to iatrogenic hyperthyroidism and oxidative stress that can cause patient discomfort. Oxidative stress is also recognized as one of the causes of chronic diseases and cancer. Methods The prevalence of breast, colorectal, gastric and lung cancer in 18 Italian Regions during 2010 was correlated with the sales of LT 4 in 2009. The cancer prevalence was analyzed in women aged 30–84. This age range corresponds to more than 80% of the consumers of the drug and to about 99% of all malignant cancers. The correlation between sales of LT 4 and cancers was determined with the technique of Density Ellipses. The age and smoking contribution for lung cancer was determined with the Sequential test. Results No significant correlation was seen between LT 4 sales and breast, colorectal and gastric cancers. A significant correlation was instead found for lung cancer (p < 0.05) corrected for smoking and age. Conclusions LT 4 consumption in Italy is about 0.7 boxes/women/year. There is a correlation between lung cancer and LT 4 treatment and oxidative stress caused by LT 4 supplementation can be one of the causes. Although we cannot exclude that dysthyroidism needing LT 4 supplementation might be the ground for lung cancer itself and measuring oxidative stress could be helpful in avoiding excessive use of the drug.

Diarrhea-predominant irritable bowel syndrome (IBS-D) is a functional gastrointestinal disorder characterized by altered motility, abdominal pain, and dysbiosis—particularly reduced biodiversity and a lower abundance of butyrate-producing bacteria. Strategies that modulate the gut microbiota may offer therapeutic benefit. Clostridium butyricum (C. butyricum) CBM588 is a butyrate-producing probiotic with immunomodulatory properties and potential efficacy in treating gastrointestinal disorders. This pragmatic, prospective, open-label, single-arm interventional study assessed the clinical, microbial, and safety-related effects of an 8-week CBM588 supplementation, along with a low-fiber and low-residue diet, in 205 patients with IBS-D who attended Quisisana Nursing Home Hospital, Rome, Italy, between November 2024 and February 2025. The primary outcomes included the global symptom response, the Bristol Stool Scale (BSS), stool frequency, diarrhea episodes, abdominal pain (severity and frequency), bloating, bowel dissatisfaction, quality of life (QoL), safety, and treatment tolerability—measured using the IBS Symptom Severity Scale (IBS-SSS) and a standardized tolerability scale. CBM588, in patients treated with a low-fiber and low-residue diet, significantly improved all clinical endpoints, with a >80% reduction in diarrhea episodes; ~60% reductions in stool frequency and abdominal pain; and >50% improvements in bloating, bowel dissatisfaction, and QoL. Treatment was well tolerated (mean tolerability score 8.95 ± 0.88), with >95% adherence, and no serious adverse events were reported. The secondary outcomes included changes in gut microbiota. In a subset of patients, 16S rRNA gene sequencing showed increased α-diversity and enrichment of butyrate-producing genera (Agathobacter, Butyricicoccus, Coprococcus), which correlated with symptom improvement. Bloating increased in some patients, possibly related to fermentation activity. These findings support the C. butyricum CBM588 probiotic strain as a safe, well-tolerated, and microbiota-targeted intervention for IBS-D. Randomized controlled trials are warranted to confirm efficacy.

Anatomical and physiological considerations indicate that the oral cavity is a primary source of the lung microbiota community, and recent studies have shown that the microbiota in the lungs contributes to immunological homeostasis, potentially altering the organ’s susceptibility to viral infection, including SARS-CoV-2. It has been proposed that, in the case of viral infection, lung Gram-negative bacteria could promote the cytokine cascade with a better performance than a microbiota mainly constituted by Gram-positive bacteria. Recent observations also suggest that Prevotella-rich oral microbiotas would dominate the oral cavity of SARS-CoV-2-infected patients. In comparison, Streptococcus-rich microbiotas would dominate the oral cavity of healthy people. To verify if the modulation of the oral microbiota could have an impact on the current coronavirus disease, we administered for 14 days a well-recognized and oral-colonizing probiotic (S. salivarius K12) to hospitalized COVID-19 patients. The preliminary results of our randomized and controlled trial seem to prove the potential role of this oral strain in improving the course of the main markers of pathology, as well as its ability to apparently reduce the death rate from COVID-19. Although in a preliminary and only circumstantial way, our results seem to confirm the hypothesis of a direct involvement of the oral microbiota in the construction of a lung microbiota whose taxonomic structure could modulate the inflammatory processes generated at the pulmonary and systemic level by a viral infection.

The aim of our study was to retrospectively evaluate whether the oral administration of L. crispatus (M247) could increase pregnancy and live birth rates in women undergoing assisted reproductive technology procedures. Enrolled women (N = 160) were divided into two groups: treated (N = 80) or untreated (N = 80) with the probiotic strain. The odds ratio (OR) for a treated woman to have a clinical pregnancy (CP) was 1.56. In women aged 30–40 years, M247 increased the probability of a CP in correlation with the progressive rise in BMI, reaching 47% (35% in controls) with a BMI of 35 (OR: 2.00). The CAID statistics showed that in a woman of the blastocyst subgroup, below 43 years, with a BMI over 18.6, treatment with M247 increased the chance of a CP from 28.4% to 44.5% (OR: 2.08; p < 0.05). Considering live births, the rate of the probiotic group was 12.5% versus 7.5% (OR: 1.76). Considering only the blastocyst subgroup, the treatment increased the number of live births by 200% (OR: 3.64; p = 0.05). As confirmed also by statistical indices NNT, NNH, and LHH, the use of M247 demonstrated a risk-benefit ratio to the full advantage of the benefits.

The conservation and sustainable use of marine resources is a highlighted goal on a growing number of national and international policy agendas. Unfortunately, efforts to assess progress, as well as to strategically plan and prioritize new marine conservation measures, have been hampered by the lack of a detailed, comprehensive biogeographic system to classify the oceans. Here we report on a new global system for coastal and shelf areas: the Marine Ecoregions of the World, or MEOW, a nested system of 12 realms, 62 provinces, and 232 ecoregions. This system provides considerably better spatial resolution than earlier global systems, yet it preserves many common elements and can be cross-referenced to many regional biogeographic classifications. The designation of terrestrial ecoregions has revolutionized priority setting and planning for terrestrial conservation; we anticipate similar benefits from the use of a coherent and credible marine system.

Context: Cancer-related fatigue (CRF) is one of the most burdensome symptoms in breast cancer survivors (BCSs), accompanied by reduced health-related quality of life (HRQOL). Objectives: This study investigated the influence of a multimodal therapy (MT; psychoeducation, eurythmy therapy, painting therapy, and sleep education/restriction), or a combination therapy (CT; MT plus aerobic training [AT]) on HRQOL in BCS with chronic CRF in comparison with AT alone. Methods: One hundred and twenty-six BCSs with CRF were included in a pragmatic comprehensive cohort study and allocated either per randomization or by preference to MT, CT, or AT. The EORTC QLQ-C30 core questionnaire was used to measure HRQOL. All analyses on HRQOL parameters were done in an explorative intention. Results: Patients were assigned to MT (n = 44), CT (n = 54), or AT (n = 28). CT was significantly superior to AT after 10 weeks of intervention (T1) in improving physical function. MT was found to have significant superiority over AT at T1 and T2 for physical functioning, emotional functioning, insomnia, and financial problems as well as role functioning, cognitive, social functioning, and fatigue 6 months later (T2). Conclusion: A multimodal approach appears to be a suitable concept for BCS with chronic CRF. A confirmatory study with larger samples should demonstrate the superiority of MT and adapted CT in HRQOL compared with the current treatment AT found in these explorative analyses.

This phase II trial evaluates, for the first time, the safety and efficacy of bendamustine plus high-dose melphalan (HDM) as a conditioning regimen before the second autologous stem cell transplantation (ASCT) in previously untreated multiple myeloma (MM) patients. In total, 32 ASCT patients received HDM (200 mg/m 2 ) as conditioning for the first ASCT. After 3–6 months from the first ASCT, responding patients underwent a second ASCT following bendamustine (200 mg/m 2 ) and HDM (140 mg/m 2 ). High-dose chemotherapy and ASCT were performed with complete neutrophil and platelet recovery in all patients. The median number of days to neutrophil and platelet engraftment was 11 (range 9–15) and 12 (range 10–19), respectively. Only one subject experienced grade 3 diarrhea; the rate of mucositis and vomiting was significantly lower with the bendamustine plus HDM regimen compared with the HDM-only regimen (81.2 vs 96.9%, P =0.025 and 78.1 vs 100%, P =0.008). Overall response rate (ORR) was 81.2% after the first transplant, and 90.6% after the second, while complete response rates were 46.8 and 62.5%, respectively ( P =0.016). Actuarial 2-year PFS and OS were 79% (95% confidence interval (CI), 60–98) and 97% (95% CI, 91–100), respectively. Bendamustine+HDM is feasible as the conditioning regimen for second ASCT in MM patients. The present study may pave the way for phase III studies specifically aimed at further investigating this combination strategy. The role of this combination in MM for conditioning regimen in a first or single ASCT setting should be also investigated.