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Abstract Age is a risk factor for hematologic malignancies. Attributes of the aging hematopoietic system include increased myelopoiesis, impaired adaptive immunity, and a functional decline of the hematopoietic stem cells (HSCs) that maintain hematopoiesis. Changes in the composition of diverse HSC subsets have been suggested to be responsible for age-related alterations, however, the underlying regulatory mechanisms are incompletely understood in the context of HSC heterogeneity. In this study, we investigated how distinct HSC subsets, separated by CD49b, functionally and molecularly change their behavior with age. We demonstrate that the lineage differentiation of both lymphoid-biased and myeloid-biased HSC subsets progressively shifts to a higher myeloid cellular output during aging. In parallel, we show that HSCs selectively undergo age-dependent gene expression and gene regulatory changes in a progressive manner, which is initiated already in the juvenile stage. Overall, our studies suggest that aging intrinsically alters both cellular and molecular properties of HSCs.

Background: To evaluate the role of targeted antibiotic prophylaxis (TAP) after rectal and urethral swab cultures compared to empiric antibiotic prophylaxis (EAP) for the prevention of infectious complications after transrectal ultrasound-guided prostate biopsy (TRUS-Bx). Methods: We conducted a prospective comparative study on 141 patients who underwent TRUS-Bx and were allocated in two groups. The first group (n = 71) received EAP with ciprofloxacin and the second (n = 70) received TAP according to rectal and urethral cultures. Post-biopsy infectious complications rates were compared between the two groups. Fluoroquinolone resistance (FQ-R) in the urethral and rectal swabs was recorded. Baseline characteristics were analyzed to assess their relationship with infectious complications and antibiotic resistance. Results: A total of 8 infectious complications were observed, 7 of them in the EAP group (9.85%) and 1 in the TAP group (1.4%). There was a statistically significant difference in febrile UTIs between the two groups (6 vs 0, P = 0.028). FQ-R rate was 4.3% and 12.9% for rectal and urethral samples, respectively. Recent antibiotic exposure was associated with higher post-biopsy infection rates for EAP group and FQ-R rates for TAP group. Conclusion: Combination of rectal and urethral swab cultures for TAP was able to detect FQ-R bacteria carriers and was associated with fewer infectious complications compared to EAP.

Background The risk of recurrence after nephrectomy for primary clear cell renal cell carcinoma (ccRCC) is estimated in daily practice solely based on clinical criteria. The aim of this study was to assess the prognostic relevance of common somatic mutations with respect to tumor aggressiveness and outcomes of ccRCC patients after definitive treatment. Methods Primary tumors from 37 patients with ccRCC who underwent radical nephrectomy were analyzed for presence of somatic mutations using a 15-gene targeted next-generation sequencing (NGS) panel. Associations to histopathologic characteristics and outcomes were investigated in the study cohort (n=37) and validated in The Cancer Genome Atlas (TCGA) ccRCC cohort (n=451). Results VHL was the most frequently mutated gene (51%), followed by PBRM1 (27%), BAP1 (13%), SETD2 (13%), KDM5C (5%), ATM (5%), MTOR (5%), and PTEN (3%). One-third of patients did not have any somatic mutations within the 15-gene panel. The vast majority of tumors harboring no mutations at all or VHL-only mutations (51%) were more frequently of smaller size (pT1-2) and earlier stage (I/II), whereas presence of any other gene mutations in various combinations with or without VHL was enriched in larger (pT3) and higher stage tumors (III) (p=0.02). No recurrences were noted in patients with unmutated tumors or VHL-only mutations as opposed to three relapses in patients with non- VHL somatic mutations (p=0.06). Presence of somatic mutations in PBRM1, BAP1, SETD2, KDM5C, ATM, MTOR, or PTEN genes in 451 TCGA ccRCC patients was associated with a significantly shorter disease-free survival (DFS) compared to those with unaltered tumors (q=0.01). Conclusions Preliminary findings from this ongoing study support the prognostic value of non- VHL mutations including PBRM1, BAP1, SETD2, KDM5C, ATM, MTOR, and PTEN in primary ccRCC tumors as surrogates of earlier recurrence and potential selection for adjuvant immune checkpoint inhibition.

Background The risk of recurrence after nephrectomy for primary clear cell renal cell carcinoma (ccRCC) is estimated in daily practice solely based on clinical criteria. The aim of this study was to assess the prognostic relevance of common somatic mutations with respect to tumor aggressiveness and outcomes of ccRCC patients after definitive treatment. Methods Primary tumors from 37 patients with ccRCC who underwent radical nephrectomy were analyzed for presence of somatic mutations using a 15-gene targeted next-generation sequencing (NGS) panel. Associations to histopathologic characteristics and outcomes were investigated in the study cohort (n=37) and validated in The Cancer Genome Atlas (TCGA) ccRCC cohort (n=451). Results VHL was the most frequently mutated gene (51%), followed by PBRM1 (27%), BAP1 (13%), SETD2 (13%), KDM5C (5%), ATM (5%), MTOR (5%), and PTEN (3%). One-third of patients did not have any somatic mutations within the 15-gene panel. The vast majority of tumors harboring no mutations at all or VHL-only mutations (51%) were more frequently of smaller size (pT1-2) and earlier stage (I/II), whereas presence of any other gene mutations in various combinations with or without VHL was enriched in larger (pT3) and higher stage tumors (III) (p=0.02). No recurrences were noted in patients with unmutated tumors or VHL-only mutations as opposed to three relapses in patients with non-VHL somatic mutations (p=0.06). Presence of somatic mutations in PBRM1, BAP1, SETD2, KDM5C, ATM, MTOR, or PTEN genes in 451 TCGA ccRCC patients was associated with a significantly shorter disease-free survival (DFS) compared to those with unaltered tumors (q=0.01). Conclusions Preliminary findings from this ongoing study support the prognostic value of non-VHL mutations including PBRM1, BAP1, SETD2, KDM5C, ATM, MTOR, and PTEN in primary ccRCC tumors as surrogates of earlier recurrence and potential selection for adjuvant immune checkpoint inhibition.

The complex interactions between intestinal microbiota and metabolic disorders are well-documented, with implications for glucose metabolism, energy expenditure, and intestinal permeability. Prebiotics induce beneficial changes in gut microbiota composition in prediabetes, while postbiotics can enhance gut barrier function, complementing each other to improve glucose metabolism and insulin sensitivity. This study investigated the effects of a 12-week dietary fibre (DF) supplement on gut health, metabolic function, and diet. The supplement contained konjac glucomannan (KGM), galacto-oligosaccharides (GOSs), and exopolysaccharides (EPSs) from Bifidobacterium breve. In a randomised, double-blind, placebo-controlled, parallel-group clinical trial, 53 prediabetic volunteers were randomly assigned to either a daily DF supplement (YMETA) or a placebo (cellulose microcrystalline) for 12 weeks, followed by a 4-week follow-up. Measurements included gut microbiota composition, glycated haemoglobin (HbA1c), fasting plasma glucose (FPG), plasma lipids, anthropometry, body composition, blood pressure, and dietary intake. The intervention group showed a significant increase in alpha diversity and butyrate-producing bacteria, with reductions in HbA1c and FPG levels below prediabetes thresholds. No significant changes were observed in the placebo group. This study suggests that manipulating the human gut microbiome through dietary interventions could be a promising therapeutic approach to managing prediabetes and preventing or delaying diabetes.

Numerical simulations have shown that finescale structures such as fronts are often suitable places for the generation of vertical velocities, transporting subsurface nutrients to the euphotic zone and thus modulating phytoplankton abundance and community structure. In these structures, direct in situ estimations of the phytoplankton growth rates are rare; although difficult to obtain, they provide precious information on the ecosystem functioning. Here, we consider the case of a front separating two water masses characterized by several phytoplankton groups with different abundances in the southwestern Mediterranean Sea. In order to estimate possible differences in growth rates, we measured the phytoplankton diurnal cycle in these two water masses as identified by an adaptive and Lagrangian sampling strategy. A size-structured population model was then applied to these data to estimate the growth and loss rates for each phytoplankton group identified by flow cytometry, showing that these two population parameters are significantly different on the two sides of the front and consistent with the relative abundances. Our results introduce a general method for estimating growth rates at frontal systems, paving the way for in situ exploration of finescale biophysical interactions.

Spirulina is a supplement with antioxidant and anti-inflammatory properties that may enhance performance and recovery after intense exercise. The present study aimed to investigate the effects of Spirulina Nigrita® on physical performance, and recovery markers after intense eccentric exercise in healthy moderately physically active volunteers. In a double-blind crossover design, participants were supplemented either with spirulina (42 mg Kg−1 BW per day) or a placebo for 15 days before conducting an eccentric exercise protocol using the non-dominant arm. A six-week washout period was required between conditions. Performance and mobility markers such as isometric peak torque (PTQ), ligament range of motion (ROM), and perceived muscle discomfort (VAS) were assessed and blood samples (CK, LDH) were obtained at 1, 24, 48, and 72 h post-exercise. No significant differences were noticed between the two conditions on any of the investigated markers, indicating that spirulina supplementation has no positive effect on isometric muscle performance or alleviation of exercise-induced muscle damage (EIMD) symptoms in the specific population.

Dietary protein with adequate essential amino acids effectively stimulates protein synthesis and improves muscle mass. Musculoskeletal disorders in lower or upper limbs are not uncommon among patients with type II diabetes mellitus (T2DM). Therefore, this study primarily examines the effects of chronic dietary protein manipulation on amino acids’ profile and position sense in the elderly suffering from T2DM. A total of 26 individuals suffering from non-insulin-dependent T2DM (age > 55 years old) participated in a 12 week nutritional intervention. The subjects were randomly assigned and the control group received 0.8–1.0 g protein/kg/day, while the intervention group received 1.2–1.5 g protein/kg/day. Lean body mass, muscle strength, and position sense were assessed at baseline, as well as at the 6th and 12th week of the intervention. Only in the intervention group, the essential amino acids intake met the current nutritional recommendations (p < 0.05), while, by the 12th week, only the intervention group showed significant improvement in the muscle strength of knee (p < 0.05) and shoulder (p < 0.05) extension. On the contrary, in the control group, a significant decline in appendicular lean mass (p < 0.05) was observed by the 12th week. Position sense at the knee joint revealed a tendency for improvement in the intervention group by the 12th week (main effect of time p = 0.072). In the present investigation, it was revealed that the higher protein intake in the intervention group seemed to have positive effects on muscle strength and nearly positive effects on position sense.

Testicular germ cell tumors (TGCTs) are the leading cause of cancer-related death in males between the ages of 20 and 40. In the advanced stages, the combination of cisplatin-based chemotherapy and surgical excision of the remaining tumor can cure many of these patients. Vascular procedures may be required during retroperitoneal lymph node dissection (RPLND) in order to achieve the complete excision of all residual retroperitoneal masses. Careful assessment of pre-operative imaging and the identification of patients who could benefit from additional procedures are important for minimizing peri- and postoperative complications. We report on a case of a 27-year-old patient with non-seminomatous TGCT, who successfully underwent post-chemotherapy RPLND with additional infrarenal inferior vena cava (IVC) and complete abdominal aorta replacement using synthetic grafts.

Lipid mediators are a class of signaling molecules that play important roles in various physiological processes, including inflammation, blood pressure regulation, and energy metabolism. Exercise has been shown to affect the production and metabolism of several types of lipid mediators, including prostaglandins, leukotrienes, sphingolipids, platelet-activating factors and endocannabinoids. Eicosanoids, which include prostaglandins and leukotrienes, are involved in the regulation of inflammation and immune function. Endocannabinoids, such as anandamide and 2-arachidonoylglycerol, are involved in the regulation of pain, mood, and appetite. Pro-resolving lipid mediators are involved in the resolution of inflammation. Sphingolipids have a role in the function of skeletal muscle during and after exercise. There are many studies that have examined the effects of exercise on the production and release of these and other lipid mediators. Some of these studies have focused on the effects of exercise on inflammation and immune function, while others have examined the effects on muscle function and metabolism. However, much less is known about their involvement in the phenomenon of exercise-induced muscle damage that follows after intense or unaccustomed exercise.

IntroductionPhase angle (PA) is derived from bioelectrical impedance analysis (BIA). It reflects cell membrane function and decreases in disease. It is affected by inflammation, oxidative stress, and diet. Platelet-activating factor (PAF) is a potent inflammatory lipid mediator. Its levels, along with the activity of its metabolic enzymes, including CDP-choline:1-alkyl-2-acetyl-sn-glycerol-cholinephosphotransferase, acetyl-CoA:lyso-PAF-acetyltransferases, and PAF-AH/Lp-PLA2 are also related to dietary factors, such as the dietary antioxidant capacity (DAC). The aim of the study was to estimate whether the PAF metabolic circuit and related dietary factors are associated with PA in healthy volunteers.MethodsIn healthy subjects, PAF, its metabolic enzyme activity, and erythrocyte fatty acids were measured, while desaturases were estimated. Food-frequency questionnaires and recalls were used, and food groups, macronutrient intake, MedDietScore, and DAC were assessed. Lifestyle and biochemical variables were collected. DXA and BIA measurements were performed.ResultsLp-PLA2 activity was positively associated with PA (rho = 0.651, p < 0.001, total population; rho = 0.780, p < 0.001, women), while PAF levels were negatively associated with PA only in men (partial rho = −0.627, p = 0.012) and inversely related to DAC. Estimated desaturase 6 was inversely associated with PA (rho = −0.404, p = 0.01, total sample). Moreover, the DAC correlated positively with PA (rho = 0.513, p = 0.03, women). All correlations were adjusted for age, body mass index, and sex (if applicable).ConclusionPA is associated with PAF levels and Lp-PLA2 activity in a gender-dependent fashion, indicating the involvement of PAF in cell membrane impairment. The relationship of PA with DAC suggests a protective effect of antioxidants on cellular health, considering that antioxidants may inhibit PAF generation.

This study evaluated the effects of dietary supplementation with a postbiotic extract of Bifidobacterium breve BB091109 on pro-inflammatory cytokines levels and markers of endocrine function. A prospective, double-blind, placebo-controlled, randomized, single-centered, parallel study was conducted on a group of 40–55-year-old females. The study included 30 healthy females, divided into two groups: a supplement (n = 20) and a placebo (n = 10) groups. Blood and saliva samples were collected at baseline (wk0), after 4 weeks (wk 4) and 12 weeks (12wk) of daily supplementation (500 mg), and 4 weeks (wk 16) after termination of supplementation. The levels of fasting CRP, IL-6, IL-10, TNF-α, IFN-γ, DHEA, estradiol, estriol, progesterone, cortisol and human growth hormone were analysed. The results revealed a significant effect of the 90-day supplementation with B. breve postbiotic extract on changes in CRP, IL-6 levels, DHEA, estradiol and estriol. In conclusion, the supplementation with the B. breve postbiotic extract improved endocrine function in females over 40 years old and induced protective changes in inflammatory markers. These findings highlight the potential health benefits of this supplementation in promoting hormonal balance and reducing inflammation in this population.

In this paper we analyse the impact of different living conditions on the length of the femur, as a proxy for stature, of three Mediterranean samples with known historical contexts, and assess sex differentials in femur length changes. The first collection analysed is composed of 18th century plague victims who had suffered several previous starvation episodes. The second collection, from the 19th century, lived through comparatively better times. The third is from the 20th century, when living conditions were better than during the two previous centuries. We compared the femur lengths of females and males between the three collections using Mann-Whitney-Wilcoxon statistical tests. The median value of male femur lengths increased over time, as expected. However, the median values of the female sample decreased in the 19th century, while the differences between the 18th and the 20th centuries samples were not statistically significant. The samples from the 18th and 20th centuries are reliable sources, but for the 19th century collection, we have assumed a possible bias in the socio-economic representativeness of the female sample. While different trends in sexual dimorphism in stature have been observed in other studies, the non-significant difference between female femur length from the 18th and the 20th centuries is unexpected, given improvements in living conditions.

Gallstone ileus is an uncommon complication of cholelithiasis and occurs when a gallstone migrates through a cholecystoenteric fistula and impacts within the gastrointestinal tract. Surgical intervention remains the treatment of choice, which consists of a full-thickness incision of the visceral wall and removal of the impacted gallstone. In this paper we present the treatment approach of 6 cases of gallstone ileus in octogenarians. In our cohort, intestinal obstruction was resolved through an enterotomy or gastrotomy and lithotomy/stone extraction in every patient. No cholecystectomies were undertaken. Despite the fact that gallstone ileus is diagnosed in small percent of patients suffering from gallstone disease, it accounts for a large proportion of intestine obstruction in patients older than 65 years old. Since accurate diagnosis and timely intervention are vital, providers should be familiar with the diagnostic approach and the treatment of this clinical entity.

Background: This single-center, retrospective study was performed to investigate the safety and efficacy of radiofrequency-assisted (RF), laparoscopic partial nephrectomy (PN) with zero ischemia in patients with low-complexity small renal tumors. Materials and Methods: Patients with small renal masses (SRMs) who underwent laparoscopic, clampless laparoscopic partial nephrectomy - radiofrequency assisted (LPN-RFA) between January 2016 and June 2020 were studied. Demographics, clinical and pathological characteristics, recurrence-free survival, and overall survival were recorded. Results: Fifty-two SRMs were excised from corresponding patients using RFA–LPN. The median tumor size was 2.5 cm and all specimens involved low-complexity masses according to the renal nephrometry score. No conversions to radical nephrectomy were recorded. Postoperatively, there were one patient with fever, one with hematuria, and two with urinary leakage treated endoscopically. The majority of tumors (48/52, 86.2%) were clear-cell carcinomas. According to the glomerular filtration rate postoperatively and 12 months' posttreatment, adequate renal function was preserved in all patients. There were no positive surgical margins identified postoperatively and no recurrences during a median follow-up 24 months. All patients were alive at the last follow-up. Conclusions: This study suggests that RFA laparoscopic clampless PN represents an effective method for managing patients with low-complexity SRMs. It offers adequate intraoperative safety and excellent mid-term oncological control and functional preservation.

The study of extreme weather events and their impact on ocean physics and biogeochemistry is challenging due to the difficulty involved with collecting in situ data. However, recent research has pointed out the major influence of such physical forcing events on microbiological organisms. Moreover, the occurrence of such intense events may increase in the future in the context of global change. In May 2019, an intense storm occurred in the Ligurian Sea (north-western Mediterranean Sea) and was captured during the FUMSECK (Facilities for Updating the Mediterranean Submesoscale – Ecosystem Coupling Knowledge) cruise. In situ multi-platform (vessel-mounted acoustic Doppler current profiler, thermosalinometer, fluorometer, flow cytometer, a moving vessel profiler equipped with a multi-sensor towed vehicle, and a glider) measurements along with satellite data and a 3D atmospheric model were used to characterise the fine-scale dynamics occurring in the impacted oceanic zone. The most affected area was marked by a lower water temperature (1 ∘C colder), a factor of 2 increase in surface chlorophyll a, and a factor of 7 increase in the nitrate concentration, exhibiting strong gradients with respect to the surrounding waters. Our results show that this storm led to a deepening of the mixed-layer depth from 15 to 50 m and a dilution of the deep chlorophyll maximum. As a result, the surface biomass of most phytoplankton groups identified by automated flow cytometry increased by up to a factor of 2. Conversely, the carbon / chlorophyll ratio of most phytoplankton groups decreased by a factor of 2, evidencing significant changes in the phytoplankton cell composition. These results suggest that the role of storms on the biogeochemistry and ecology of the Mediterranean Sea may be underestimated and highlight the need for high-resolution measurements during these events coupling physics and biology.

Background: The risk of recurrence after nephrectomy for primary clear cell renal cell carcinoma (ccRCC) is estimated in daily practice solely based on clinical criteria. The aim of this study was to assess the prognostic relevance of common somatic mutations with respect to tumor aggressiveness and outcomes of ccRCC patients after definitive treatment. Methods: Primary tumors from 37 patients with ccRCC who underwent radical nephrectomy were analyzed for presence of somatic mutations using a 15-gene targeted next-generation sequencing (NGS) panel. Associations to histopathologic characteristics and outcomes were investigated in the study cohort (n=37) and validated in The Cancer Genome Atlas (TCGA) ccRCC cohort (n=451). Results: VHL was the most frequently mutated gene (51%), followed by PBRM1 (27%), BAP1 (13%), SETD2 (13%), KDM5C (5%), ATM (5%), MTOR (5%), and PTEN (3%). One-third of patients did not have any somatic mutations within the 15-gene panel. The vast majority of tumors harboring no mutations at all or VHL-only mutations (51%) were more frequently of smaller size (pT1-2) and earlier stage (I/II), whereas presence of any other gene mutations in various combinations with or without VHL was enriched in larger (pT3) and higher stage tumors (III) (p=0.02). No recurrences were noted in patients with unmutated tumors or VHL-only mutations as opposed to three relapses in patients with non- VHL somatic mutations (p=0.06). Presence of somatic mutations in PBRM1, BAP1, SETD2, KDM5C, ATM, MTOR, or PTEN genes in 451 TCGA ccRCC patients was associated with a significantly shorter disease-free survival (DFS) compared to those with unaltered tumors (q=0.01). Conclusions: Preliminary findings from this ongoing study support the prognostic value of non- VHL mutations including PBRM1, BAP1, SETD2, KDM5C, ATM, MTOR, and PTEN in primary ccRCC tumors as surrogates of earlier recurrence and potential selection for adjuvant immune checkpoint inhibition.