A Single Kinase Generates the Majority of the Secreted Phosphoproteome.

The existence of extracellular phosphoproteins has been acknowledged for over a century. However, research in this area has been undeveloped largely because the kinases that phosphorylate secreted proteins have escaped identification. Fam20C is a kinase that phosphorylates S-x-E/pS motifs on proteins in milk and in the extracellular matrix of bones and teeth. Here, we show that Fam20C generates the majority of the extracellular phosphoproteome. Using CRISPR/Cas9 genome editing, mass spectrometry, and biochemistry, we identify more than 100 secreted phosphoproteins as genuine Fam20C substrates. Further, we show that Fam20C exhibits broader substrate specificity than previously appreciated. Functional annotations of Fam20C substrates suggest roles for the kinase beyond biomineralization, including lipid homeostasis, wound healing, and cell migration and adhesion. Our results establish Fam20C as the major secretory pathway protein kinase and serve as a foundation for new areas of investigation into the role of secreted protein phosphorylation in human biology and disease.

Coenzyme Q10 trapping in mitochondrial complex I underlies Leber's hereditary optic neuropathy.

How does a single amino acid mutation occurring in the blinding disease, Leber's hereditary optic neuropathy (LHON), impair electron shuttling in mitochondria? We investigated changes induced by the m.3460 G>A mutation in mitochondrial protein ND1 using the tools of Molecular Dynamics and Free Energy Perturbation simulations, with the goal of determining the mechanism by which this mutation affects mitochondrial function. A recent analysis suggested that the mutation's replacement of alanine A52 with a threonine perturbs the stability of a region where binding of the electron shuttling protein, Coenzyme Q10, occurs. We found two functionally opposing changes involving the role of Coenzyme Q10. The first showed that quantum electron transfer from the terminal Fe/S complex, N2, to the Coenzyme Q10 headgroup, docked in its binding pocket, is enhanced. However, this positive adjustment is overshadowed by our finding that the mobility of Coenzyme Q10 in its oxidized and reduced states, entering and exiting its binding pocket, is disrupted by the mutation in a manner that leads to conditions promoting the generation of reactive oxygen species. An increase in reactive oxygen species caused by the LHON mutation has been proposed to be responsible for this optic neuropathy.

Oxidative stress reduction by icodextrin-based glucose-free solutions in peritoneal dialysis: Support for new promising approaches.

BACKGROUND: Oxidative stress (OxSt) and inflammation are common in CKD and are known CV and mortality risk factors. In peritoneal dialysis (PD) OxSt and Inflammation even increase due to the use of glucose-based solutions. PATIENTS AND METHODS: This study analyzed in 15 PD patients the effect of 3 and 6 months of treatment with icodextrin-based glucose-free solutions on OxSt and inflammation, evaluating p22phox protein expression (Western blot), NADPH oxidase subunit, essential for OxSt activation, MYPT-1 phosphorylation state, marker of RhoA/Rho kinase pathway (ROCK) activity, involved in the induction of OxSt (Western blot) and Malondialdehyde (MDA) production (fluorimetric assay). Interleukin (IL)-6 blood level (chemiluminescence assay) has been measured and used as a marker of inflammation. RESULTS: p22phox protein expression, MYPT 1 phosphorylation, and MDA were reduced after 3 months from the start of icodextrin (1.28 ± 0.18 d.u. vs. 1.50 ± 0.19, p = 0.049; 0.89 ± 0.03 vs. 0.98 ± 0.03, p = 0.004; 4.20 ± 0.18 nmol/mL vs. 4.84 ± 0.32 nmol/mL, p = 0.045, respectively). In a subgroup of 9 patients who continued the treatment up to 6 months, MYPT-1 phosphorylation was further reduced at 6 months compared to baseline (0.84 ± 0.06 vs. 0.99 ± 0.04, p = 0.043), while p22phox protein expression was reduced only at 6 months versus baseline (1.03 ± 0.05 vs. 1.68 ± 0.22, p = 0.021). In this subgroup, MDA was reduced at 6 months versus baseline (4.03 ± 0.24 nmol/mL vs. 4.68 ± 0,32, p = 0.024) and also versus 3 months (4.03 ± 0.24 vs. 4.35 ± 0.21, p = 0.008). IL-6 level although reduced both at 3 and 6 months, did not reach statistical significance. CONCLUSIONS: The reduction of OxSt with icodextrin-based PD solutions, although obtained in a small patients cohort and in a limited time duration study, strongly supports the rationale of using osmo-metabolic agents-based fluids replacing glucose-based fluids. Ongoing studies with these agents will provide information regarding preservation of peritoneal membrane integrity, residual renal function, and reduction of CVD risk factors such as OxSt and inflammation.

Effect of Kinesio taping on wrist proprioception in healthy subjects: A randomized clinical trial.

BACKGROUND: Although the use of KT has increased considerably in the clinical practice in the last years, there is limited evidence about the effects of its application in proprioception. PURPOSE: The aim of this study was to determine the effect of KT on joint position sense and force sense on the wrist of healthy subjects. METHODS: Fifty-four subjects were analyzed in a randomized, crossover, single-blind study design. To determine the force sense, the subjects had to reach 50% of their maximum grip force. Wrist joint position sense was assessed during active repositioning tests at the target angles of 30° flexion and extension of wrist. A digital dynamometer was used to determine the sense of force and a digital goniometer was used to determine the joint position sense. Subjects were evaluated with KT (I- strip on ventral aspect of forearms from origin to insertion) and placebo (an inelastic tape was applied following the same procedure as KT). RESULTS: No significant differences have been found in the force sense, neither in the comparisons between control and interventions (p=0.286), nor between pre and post-intervention (p=0.111). For wrist joint position sense, a statistically significant effect (p< 0.05) was found at 30º of extension between the control and experimental group in favor of the control group. CONCLUSIONS: The application of KT did not produce changes in FS and only caused a significant improvement in JPS in extension (30º). The results appear to indicate that the application of KT to improve proprioception in healthy subjects should be reconsidered.

Hemicolectomy versus appendectomy for patients with appendiceal neuroendocrine tumours 1-2 cm in size: a retrospective, Europe-wide, pooled cohort study.

BACKGROUND: Awareness of the potential global overtreatment of patients with appendiceal neuroendocrine tumours (NETs) of 1-2 cm in size by performing oncological resections is increasing, but the rarity of this tumour has impeded clear recommendations to date. We aimed to assess the malignant potential of appendiceal NETs of 1-2 cm in size in patients with or without right-sided hemicolectomy. METHODS: In this retrospective cohort study, we pooled data from 40 hospitals in 15 European countries for patients of any age and Eastern Cooperative Oncology Group performance status with a histopathologically confirmed appendiceal NET of 1-2 cm in size who had a complete resection of the primary tumour between Jan 1, 2000, and Dec 31, 2010. Patients either had an appendectomy only or an appendectomy with oncological right-sided hemicolectomy or ileocecal resection. Predefined primary outcomes were the frequency of distant metastases and tumour-related mortality. Secondary outcomes included the frequency of regional lymph node metastases, the association between regional lymph node metastases and histopathological risk factors, and overall survival with or without right-sided hemicolectomy. Cox proportional hazards regression was used to estimate the relative all-cause mortality hazard associated with right-sided hemicolectomy compared with appendectomy alone. This study is registered with ClinicalTrials.gov, NCT03852693. FINDINGS: 282 patients with suspected appendiceal tumours were identified, of whom 278 with an appendiceal NET of 1-2 cm in size were included. 163 (59%) had an appendectomy and 115 (41%) had a right-sided hemicolectomy, 110 (40%) were men, 168 (60%) were women, and mean age at initial surgery was 36·0 years (SD 18·2). Median follow-up was 13·0 years (IQR 11·0-15·6). After centralised histopathological review, appendiceal NETs were classified as a possible or probable primary tumour in two (1%) of 278 patients with distant peritoneal metastases and in two (1%) 278 patients with distant metastases in the liver. All metastases were diagnosed synchronously with no tumour-related deaths during follow-up. Regional lymph node metastases were found in 22 (20%) of 112 patients with right-sided hemicolectomy with available data. On the basis of histopathological risk factors, we estimated that 12·8% (95% CI 6·5 -21·1) of patients undergoing appendectomy probably had residual regional lymph node metastases. Overall survival was similar between patients with appendectomy and right-sided hemicolectomy (adjusted hazard ratio 0·88 [95% CI 0·36-2·17]; p=0·71). INTERPRETATION: This study provides evidence that right-sided hemicolectomy is not indicated after complete resection of an appendiceal NET of 1-2 cm in size by appendectomy, that regional lymph node metastases of appendiceal NETs are clinically irrelevant, and that an additional postoperative exclusion of metastases and histopathological evaluation of risk factors is not supported by the presented results. These findings should inform consensus best practice guidelines for this patient cohort. FUNDING: Swiss Cancer Research foundation.

How can a traffic light properly work if it is always green? The paradox of CK2 signaling.

CK2 is a constitutively active protein kinase that assuring a constant level of phosphorylation to its numerous substrates supports many of the most important biological functions. Nevertheless, its activity has to be controlled and adjusted in order to cope with the varying needs of a cell, and several examples of a fine-tune regulation of its activity have been described. More importantly, aberrant regulation of this enzyme may have pathological consequences, e.g. in cancer, chronic inflammation, neurodegeneration, and viral infection. Our review aims at summarizing our current knowledge about CK2 regulation. In the first part, we have considered the most important stimuli shown to affect protein kinase CK2 activity/expression. In the second part, we focus on the molecular mechanisms by which CK2 can be regulated, discussing controversial aspects and future perspectives.

Nanoscale organization of CaV2.1 splice isoforms at presynaptic terminals: implications for synaptic vesicle release and synaptic facilitation.

The distance between CaV2.1 voltage-gated Ca2+ channels and the Ca2+ sensor responsible for vesicle release at presynaptic terminals is critical for determining synaptic strength. Yet, the molecular mechanisms responsible for a loose coupling configuration of CaV2.1 in certain synapses or developmental periods and a tight one in others remain unknown. Here, we examine the nanoscale organization of two CaV2.1 splice isoforms (CaV2.1[EFa] and CaV2.1[EFb]) at presynaptic terminals by superresolution structured illumination microscopy. We find that CaV2.1[EFa] is more tightly co-localized with presynaptic markers than CaV2.1[EFb], suggesting that alternative splicing plays a crucial role in the synaptic organization of CaV2.1 channels.

Skin lesions by Scedosporium apiospermum and Nocardia pulmonary infection in an oncologic patient: a case report.

BACKGROUND: Fungal infections, other than candidiasis and aspergillosis, are an uncommon entity. Despite this, emerging pathogens are a growing threat. In the following case report, we present the case of an immunocompromised patient suffering from two serious opportunistic infections in the same episode: the first of these, Nocardia multilobar pneumonia; and the second, skin infection by Scedosporium apiospermum. These required prolonged antibacterial and antifungal treatment. CASE PRESENTATION: This case is a 71-year-old oncological patient admitted for recurrent pneumonias that was diagnosed for Nocardia pulmonary infection. Nervous system involvement was discarded and cotrimoxazole was started. Haemorrhagic skin ulcers in the lower limbs appeared after two weeks of hospital admission. We collected samples which were positive for Scedosporium apiospermum and we added voriconazole to the treatment. As a local complication, the patient presented a deep bruise that needed debridement. We completed 4 weeks of intravenous treatment with slow improvement and continued with oral treatment until the disappearance of the lesions occurs. CONCLUSIONS: Opportunistic infections are a rising entity as the number of immunocompromised patients is growing due to more use of immunosuppressive therapies and transplants. Clinicians must have a high suspicion to diagnose and treat them. A fluid collaboration with Microbiology is necessary as antimicrobial resistance is frequent.

Can Music Decrease Anxiety and Pain During Dental Implant Surgery? A Randomized Clinical Trial.

PURPOSE: Music has proven to be an effective tool in the management of anxiety during some surgical procedures. The aim of this study was to test the effect of baroque (BM) and classical era music (CM) as a nonpharmacological therapy on the control of anxiety and pain levels among patients undergoing dental implant placement surgery. METHODS: A randomized controlled clinical trial of patients attending a dental clinic was conducted. Patients with psychiatric disorders were excluded. Twenty six patients of Spanish nationality requiring single-tooth dental implant were included. Each patient was assigned to 1 of the 3 experimental groups, which acted as an independent variable: Group I (n = 8) listened to BM; Group II (n = 10) listened to CM; and Group III (n = 8) did not listen to music and was the control group (C). The dependent variables were divided into physiological variables and psychological variables. The physiological dependent variables analysed were systolic and diastolic blood pressure, heart rate, and oxygen saturation, recorded at 4 different times during surgery. The Kruskal-Wallis test compared each of these variables between the 3 experimental groups. The psychological dependent variable analyzed was the degree of anxiety, measured by the self-completed Modified Dental Anxiety Scale and Visual Analog Scale (measured before and after surgery). The Wilcoxon statistical test compared degree of anxiety before and after surgery. In all cases, the level of statistical significance was set at P < .05. RESULTS: The mean age of the sample was 46.5 ± 10.6 (range, 24-69 years), 50% male and 50% female. Statistically significant differences in degree of anxiety before and after surgery were found in the BM (P = .027, confidence interval [CI] = 0.146-6.104; BM before = 4.25 ± 3.91 and BM after = 1.13 ± 1.45) and CM groups (P = .044, CI = 0.161-3.039; CM before = 3.10 ± 2.88 and CM after = 1.50 ± 1.43) and were not found in group C (P = .180, CI = 1.104-3.604; C before = 2.63 ± 3.62 and C after = 1.38 ± 1.99). When comparing the perceived pain after the intervention among the 3 groups (C, BM, and CM), no significant differences were observed between them (P = .319; CI = -0.58-1.96; C = 0.75 ± 1.75, BM = 1.25 ± 1.75, and CM = 1.70 ± 1.70). CONCLUSION: Listening to BM and CM reduces anxiety in patients undergoing dental implant placement surgery. Musical flow should be applied in this practice.

Recovery of kicking kinematics and performance following repeated high-intensity running bouts in the heat: Can a rapid local cooling intervention help young soccer players?

The effects of a cooling strategy following repeated high-intensity running (RHIR) on soccer kicking performance in a hot environment (>30ºC) were investigated in youth soccer players. Fifteen academy under-17 players participated. In Experiment 1, players completed an all-out RHIR protocol (10×30 m, with 30s intervals). In Experiment 2 (cross-over design), participants performed this running protocol under two conditions: (1) following RHIR 5 minutes of cooling where ice packs were applied to the quadriceps/hamstrings, (2) a control condition involving passive resting. Perceptual measures [ratings of perceived exertion (RPE), pain and recovery], thigh temperature and kick-derived video three-dimensional kinematics (lower limb) and performance (ball speed and two-dimensional placement indices) were collected at baseline, post-exercise and intervention. In Experiment 1, RHIR led to small-to-large impairments (p < 0.03;d = -0.42--1.83) across perceptual, kinematic and performance measures. In experiment 2, RPE (p < 0.01; Kendall's W = 0.30) and mean radial error (p = 0.057; η2 = 0.234) increased only post-control. Significant small declines in ball speed were also observed post-control (p < 0.05; d = 0.35). Post-intervention foot centre-of-mass velocity was moderately faster in the cooling compared to control condition (p = 0.04; d = 0.60). In youth soccer players, a short cooling period was beneficial in counteracting declines in kicking performance, in particular ball placement, following intense running activity in the heat.

Assessing the suitability of solar dryers applied to wastewater plants: A review.

Sludge dewatering and drying are the main processes related to sludge management in wastewater treatment plants (WWTPs). Sludge disposal is a high-cost activity, and drying the sludge reduces its mass and volume, resulting in savings in storage, handling and transportation. The discoveries regarding the use of solar energy in agricultural studies provided valuable information for using in sewage sludge drying. Some studies have reported that dry sludge has met the EPA Class A requirement for biosolids using only solar energy as an energy source. The proper sludge mixture, manual or mechanical, and the dewatering process can significantly increase the drying rate, reducing drying time and the surface area needed. The environmental conditions and the sludge's type greatly influence the drying system. A solar dryer system may be suitable to dry different types of wastewater sludge. Modeling techniques can predict the behavior of the solar drying system and, thus, save time and money in experimental steps. CFD modeling of the sludge drying system is usually done by adopting specific boundary conditions and solving the Navier Stokes equations for air and sludge. There is no standard methodology for comparing solar dryers and common methodologies, such as system efficiency and thermal efficiency, disregards different dryers in different operational conditions. A SWOT (strengths, weaknesses, opportunities, and threats) analysis indicated that, in general, the chapel-type greenhouse with mixed-mode drying has higher drying rates, resulting in reduced drying time and can be scaled to any size. Thus, this type of dryer emerges as a more economical alternative to commercial solar dryers. Based on a systematic review, this work points the SWOT analysis as a useful tool for selecting solar dryers.

The safety of pneumococcal vaccines at the time of sequential schedule: data from surveillance of adverse events following 13-valent conjugated pneumococcal and 23-valent polysaccharidic pneumococcal vaccines in newborns and the elderly, in Puglia (Italy), 2013-2020.

Background: Nowadays, two types of anti-pneumococcal vaccine are available: pneumococcal 13-valent conjugate vaccine (PCV13), first licensed in the United States (US) in 2013, and pneumococcal 23-valent polysaccaridic vaccine (PPSV23), first licensed in the US in 1999. These vaccines are recommended in Italy for the immunization of newborns and of the elderly, using a combined sequential schedule for the latter. This report aims to describe the PCV13- and PPSV23-related AEFIs notified in Puglia in 2013-2020, in order to design these products' safety profile in a real-life scenario, three years after the official recommendation about the sequential schedule for people over 60 years of age. Methods: This is a retrospective observational study. Data were gathered from the list of AEFIs notified following PCV13 and PPSV23 administration in Puglia in 2013-2020. The number of administered vaccine doses was obtained from the regional immunization database. AEFIs were classified according to WHO's algorithm, and causality assessment was carried out in case of serious AEFIs. Results: From January 2013 to December 2020, 764,183 doses of PCV13 and 40,382 doses of PPSV23 were administered in Puglia. In the same period, 71 PCV13 AEFIs (Reporting Rate: 9.29 x100,000 doses) and 5 PPSV23 AEFIs (Reporting Rate: 12.4 x100,000 doses) were reported. The overall male/female ratio in AEFIs was 0.85. The majority of AEFIs occurred in subjects aged less than 2 (64/76, 84.2%), while 10 out of 76 (13.2%) occurred in patients aged 60 or older. 22 AEFIs were classified as serious and for 12 (54.5%) causality assessment showed a consistent relationship with immunization. The most commonly reported symptoms were fever (Reporting Rate: 4.72 x100,000 doses) and neurological symptoms (Reporting Rate: 3.23 x100,000 doses). Only one death was notified, classified as non-vaccine-related. Conclusions: The benefit of pneumococcal vaccination appears to be greater than the risk of AEFIs for both PCV13 and PPSV23. In fact, AEFIs occur in less than 0.1‰ of patients and the majority of AEFIs are mild and self-limiting.

Incidence of SARS-COV-2 infection among swimming athletes: data from real life in Apulia (Italy), July 2020/August 2021.

Background: As other indoor sports facilities, swimming pools were closed in Italy from March to May 2020 and from October 2020 to July 2021 due to the outbreak of the COVID-19 pandemic; access to these facilities was restricted to athletes of national relevance. This decision was based on "precautionary principles" and without evidence of a high risk of SARS-COV-2 circulation among swimming pools' attendants. The aim of this paper is to describe the pattern of SARS-COV-2 circulation among swimming athletes in Apulia (Southern Italy). Study design: The study aims to investigate the hypothesis that attending a pool increases the risk of SARS-COV-2 infection. The outcome measure is the incidence of SARS-COV-2 infection among swimming athletes compared with the general population. Methods: This is a retrospective cross-sectional study carried out in Apulia, Southern Italy. The study was performed through the analysis of both the database of the Italian Swimming Federation and the SARS-COV-2 infections in Apulia Region, from July 2020 to August 2021. Results: Among 2,939 federally licensed athletes, 221 had an history of SARS-COV-2 infection from July 2020 to August 2021, with an incidence of 75.2 /1,000. In the general Apulian population, during the same time span, the incidence of SARS-COV-2 infection was 67.3/1,000 and - considering the incidence rate ratio - there is no difference between the two populations (IRR=1.1; 95% CI=0.9-1.3; p>0.05). Conclusions: The incidence of SARS-COV-2 infection in Apulian swimmers showed no significant differences with the general population.

A new paradigm of hospital care for SARS-COV-2 patients in the post-emergency phase in Italy.

Abstract: In Italy, at the beginning of the SARS-CoV-2 pandemic, the main organizational model of hospital care was represented by the physical or functional division of hospitals and wards into COVID and non-COVID areas, in order to separate SARS-CoV-2-infected patients from the others. Now that the emergency phase has reached its long-awaited end, it is necessary to develop a new hospital care paradigm that may deal with SARS-CoV-2-positive patients discriminating between those who are hospitalized because of COVID-19 and those who are diagnosed with SARS-CoV-2 infection immediately before or after the first access to healthcare facilities.

Incidence of Hepatocellular Carcinoma in Patients With Nonalcoholic Fatty Liver Disease: A Systematic Review, Meta-analysis, and Meta-regression.

BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) may be a risk factor for hepatocellular carcinoma (HCC), but the extent of this association still needs to be addressed. Pooled incidence rates of HCC across the disease spectrum of NAFLD have never been estimated by meta-analysis. METHODS: In this systematic review, we searched Web of Science, Embase, PubMed, and the Cochrane Library from January 1, 1950 through July 30, 2020. We included studies reporting on HCC incidence in patients with NAFLD. The main outcomes were pooled HCC incidences in patients with NAFLD at distinct severity stages. Summary estimates were calculated with random-effects models. Sensitivity analyses and meta-regression analyses were carried out to address heterogeneity. RESULTS: We included 18 studies involving 470,404 patients. In patients with NAFLD at a stage earlier than cirrhosis, the incidence rate of HCC was 0.03 per 100 person-years (95% confidence interval [CI], 0.01-0.07; I2 = 98%). In patients with cirrhosis, the incidence rate was 3.78 per 100 person-years (95% CI, 2.47-5.78; I2 = 93%). Patients with cirrhosis undergoing regular screening for HCC had an incidence rate of 4.62 per 100 person-years (95% CI, 2.77-7.72; I2 = 77%). CONCLUSIONS: Patients with NAFLD-related cirrhosis have a risk of developing HCC similar to that reported for patients with cirrhosis from other etiologies. Evidence documenting the risk in patients with nonalcoholic steatohepatitis or simple steatosis is limited, but the incidence of HCC in these populations may lie below thresholds used to recommend a screening. Well-designed prospective studies in these subpopulations are needed. The protocol for this systematic review is registered in the Prospero database (registration number CRD42018092861).

Parathyroid hormone and phosphate homeostasis in patients with Bartter and Gitelman syndrome: an international cross-sectional study.

BACKGROUND: Small cohort studies have reported high parathyroid hormone (PTH) levels in patients with Bartter syndrome and lower serum phosphate levels have anecdotally been reported in patients with Gitelman syndrome. In this cross-sectional study, we assessed PTH and phosphate homeostasis in a large cohort of patients with salt-losing tubulopathies. METHODS: Clinical and laboratory data of 589 patients with Bartter and Gitelman syndrome were provided by members of the European Rare Kidney Diseases Reference Network (ERKNet) and the European Society for Paediatric Nephrology (ESPN). RESULTS: A total of 285 patients with Bartter syndrome and 304 patients with Gitelman syndrome were included for analysis. Patients with Bartter syndrome type I and II had the highest median PTH level (7.5 pmol/L) and 56% had hyperparathyroidism (PTH >7.0 pmol/L). Serum calcium was slightly lower in Bartter syndrome type I and II patients with hyperparathyroidism (2.42 versus 2.49 mmol/L; P = .038) compared to those with normal PTH levels and correlated inversely with PTH (rs -0.253; P = .009). Serum phosphate and urinary phosphate excretion did not correlate with PTH. Overall, 22% of patients had low serum phosphate levels (phosphate-standard deviation score < -2), with the highest prevalence in patients with Bartter syndrome type III (32%). Serum phosphate correlated with tubular maximum reabsorption of phosphate/glomerular filtration rate (TmP/GFR) (rs 0.699; P < .001), suggesting renal phosphate wasting. CONCLUSIONS: Hyperparathyroidism is frequent in patients with Bartter syndrome type I and II. Low serum phosphate is observed in a significant number of patients with Bartter and Gitelman syndrome and appears associated with renal phosphate wasting.

Gitelman's and Bartter's Syndromes: From Genetics to the Molecular Basis of Hypertension and More.

BACKGROUND: Gitelman's and Bartter's syndromes (GS/BS) are rare genetic tubulopathies characterized by electrolyte imbalance and activation of the renin-angiotensin-aldosterone system (RAAS). These syndromes have intriguing biochemical and hormonal abnormalities that lead them to be protected from hypertension and cardiovascular and renal remodeling. SUMMARY: In this review, we explore the biochemical/molecular mechanisms induced by the activation of the RAAS and its counterregulatory arm which is particularly activated in GS/BS patients, in the context of blood pressure regulation. In addition, we report our findings in the context of the COVID-19 pandemic where we observed GS/BS subjects being protected from infection. KEY MESSAGES: The intracellular pathways induced by Ang II, starting from induction of oxidative stress and vasoconstriction, are crucial for the progression toward cardiovascular-renal remodeling and might be useful targets in order to reduce/halt the progression of Ang II/oxidative stress-induced cardiovascular-renal morbidity in several diseases.

ICF Core Sets for the assessment of functioning of adults with cerebral palsy.

AIM: To report on the results of the online international consensus process to develop the comprehensive and brief International Classification of Functioning, Disability and Health (ICF) Core Sets for adults with cerebral palsy (CP). METHOD: An online iterative decision-making and consensus process involved 25 experts, including clinicians and researchers working with adults with CP, an adult with CP, and the parents of adults with CP from all six regions of the World Health Organization. The most relevant categories were selected from a list of 154 unique second-level candidate categories to develop the ICF Core Sets for adults with CP. This list resulted from evidence gathered during four preparatory studies, that is, a systematic literature review, a qualitative study, an expert survey, and an empirical study. RESULTS: The consensus process resulted in the comprehensive ICF Core Set containing 120 second-level ICF categories: 33 body functions; eight body structures; 50 activities and participation; and 29 environmental factors, from which the most essential categories, 33 in total, were selected for the brief ICF Core Set. For body functions, most of the categories were mental functions and neuromusculoskeletal and movement-related functions. Body structures were mostly related to movement. All the chapters of the activities and participation component were represented, with mobility and self-care as the most frequently covered chapters. For environmental factors, most of the categories addressed products and technology and services, systems, and policies. INTERPRETATION: The comprehensive and brief ICF Core Sets for adults with CP were created using a new online version of an established ICF Core Set consensus process. These Core Sets complement the age-specific ICF Core Sets for children and young people with CP and will promote standardized data collection worldwide.

In vitro use of standard fluid infusion central venous catheter for slow continuous ultrafiltration feasibility assessment.

BACKGROUND: Slow continuous ultrafiltration (SCUF) by central venous catheter (CVC) for hemodialysis is a simple extracorporeal ultrafiltration that can reduce and control fluid overload in patients with chronic or acute chronic heart failure unresponsive to medical therapy. In order to avoid complications and risks related to the catheterization with a standard CVC for hemodialysis to provide the SCUF, considering that hospitalized patients affected by congestive heart failure commonly undergo CVC placement for medications delivering, we tested an in vitro model to use a standard CVC for infusion to perform SCUF. METHODS: We performed an in vitro SCUF experimental model through two different lumens of a triple (8Fr × 20 cm Tri-lumen catheter Kit-Envans Extra) and a quad-lumen CVC (8.5Fr × 20 cm Quad-lumen catheter kit-Benefis Medical Devices) commonly used in our Intensive Care Unit for fluids and medications infusions. We used Prismaflex with the HF-20 set (Baxter, IL, USA) to perform the SCUF treatment. RESULTS: Our in vitro data confirm the technical feasibility of the use of standard CVC for fluid infusion to perform a SCUF treatment with a theoretical weight loss of up to 200 ml/h by a blood flow ranging from 30 to 45 ml/min. CONCLUSIONS: The use of standard infusion CVC could be utilized in the intensive care unit to perform SCUF not exposing patients to the risks and complications related to the placement and permanence of CVC for hemodialysis.