Elevated concentration of beta2-microglobulin among patients with carpal tunnel syndrome in the course of primary Sjögren syndrome - a prospective observational study on 50 patients.

INTRODUCTION: Sjögren's syndrome (SS) is a chronic autoimmune disease characterized by lymphocytic infiltrates in the exocrine glands. Carpal tunnel syndrome (CTS) is suggested to be more frequent among SS patients than in the general population. The aim of this study was to seek associations between the CTS and the laboratory and clinical findings of SS patients. METHODS: Fifty patients diagnosed with primary SS (pSS) were examined. Clinical evaluation by a rheumatologist and electrophysiological studies were conducted. Data on laboratory tests results was collected. Control group consisted of 50 sex and age-matched individuals with osteoarthritis (OA). RESULTS: Out of 50 patients in the study group 27 (54%) were diagnosed with CTS. The prevalence of CTS among 50 individuals in the control group was 8%. Among pSS patients with CTS the joint involvement was not more common than in those from the non-CTS group [15 vs. 13 (p = 0.945)]. There was an expected difference in sleep disorders [18 vs. 9 (p = 0.012)] and paresthesia [23 vs. 13 (p = 0.024)]. The major finding was a significant difference in elevated beta2-microglobulin (B2MG) [23 vs. 13 (p = 0.024)]. Other studied factors, suggested in the literature as significant in the pSS-related neuropathy, were not statistically different between the groups. CONCLUSION: Our study confirms that CTS is more prevalent among pSS patients than in the general population and suggests that a new approach is required towards the pathogenesis of this phenomenon. We hypothesize that CTS is more associated with an overall disease activity than joint involvement as such.

Metabolomics in systemic sclerosis.

Systemic sclerosis is a rare autoimmune condition leading to incurable complications. Therefore fast and precise diagnosis is crucial to prevent patient death and to maintain quality of life. Unfortunately, currently known biomarkers do not meet this need. To address this problem researchers use diverse approaches to elucidate the underlying aberrations. One of the methods applied is metabolomics. This modern technique enables a comprehensive assessment of multiple compound concentrations simultaneously. As it has been gaining popularity, we found it necessary to summarize metabolomic studies presented so far in a narrative review. We found 11 appropriate articles. All of the researchers found significant differences between patients and control groups, whereas the reported findings were highly inconsistent. Additionally, we have found the investigated groups in most studies were scarcely described, and the inclusion/exclusion approach was diverse. Therefore, further study with meticulous patient assessment is necessary.

Co-existence of ANCA-associated vasculitides with immune-mediated diseases: a single-center observational study.

BACKGROUND: Antineutrophil cytoplasmic antibody-associated vasculitides (AAV) is a group of systemic necrotizing small vessel autoimmune diseases, with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) being the two most common. The co-existence of AAV with different immune-mediated diseases (autoimmune disesases - AID) might affect the clinical presentation of the primary disease. The purpose of the study was to assess the co-existence of AAV with AID and to investigate whether it affects the characteristics and the course of AAV. METHODS: A retrospective single-center study was performed to identify patients with a diagnosis of MPA or GPA and concomitant AID, and to investigate their clinical features and characteristics. The group consisted of consecutive unselected AAV patients treated at a large university-based hospital, since 1988 with follow-up until 2022. RESULTS: Among 284 patients diagnosed either with GPA (232) or MPA (52), 40 (14,1%) had co-existing AIDs. The most frequent were: Hashimoto thyroiditis (16 cases), rheumatoid arthritis (8 cases), followed by psoriasis (6 cases), pernicious anemia (3 cases), and alopecia (3 cases). Patients with autoimmune comorbidities had a significantly longer time between the onset of symptoms and the diagnosis (26 vs. 11 months, p < 0.001). Laryngeal involvement (20.0% vs. 9.0%, p = 0,05), peripheral nervous system disorders (35.0% vs. 13.9%, p < 0.001), and neoplasms (20.0% vs. 8.6%, p = 0,044) were more common in patients with AID comorbidities, compared to subjects without AID. In contrast, renal involvement (45.0% vs. 70.9%, p = 0.001) and nodular lung lesions (27.5% vs. 47.5%, p = 0.044) were significantly less frequent in patients with co-morbidities. Following EUVAS criteria, patients with autoimmune co-morbidities had a generalized form of the disease without organ involvement (52.5% vs. 27.2%, p = 0.007), while the others had a higher percentage of generalized form with organ involvement (38.3% vs. 20.0%, p = 0.007). CONCLUSIONS: The coexistence of AAV with different autoimmune diseases is not common, but it might affect the clinical course of the disease. Polyautoimmunity prolonged the time to diagnosis, but the AAV course seemed to be milder. Particular attention should be paid to the increased risk of cancer in these patients. It also seems reasonable that AAV patients should receive a serological screening to exclude the development of overlapping diseases.

The use of intravascular contrast media in patients with impaired kidney function - joint clinical practice position statement of the Polish Society of Nephrology and the Polish Medical Society of Radiology.

Radiological procedures utilising intravascular contrast media (ICM) are fundamental to modern medicine, enhancing diagnostics and treatment in diverse medical fields. However, the application of ICM has been constrained in patients with compromised kidney function due to perceived nephrotoxic risks, called contrast-induced nephropathy or contrastinduced acute kidney injury. Historical evidence marked ICM as a possible contributor to kidney damage. This led to restrictive guidelines advocating limited ICM use in patients with impaired renal function, preventing crucial radiographic interventions in patients with acute kidney injury (AKI) and chronic kidney disease. Recent advances challenge these traditional views. In particular, no direct causal relationship has been confirmed between contrast admi-nistration and elevated serum creatinine concentrations in humans. Furthermore, contemporary research models and meta-analyses do not associate AKI with contrast usage. This paper, prepared by a cross-disciplinary team of nephrologists and radiologists, presents updated guidelines for ICM application amid renal function impairments, emphasising the reduced nephrotoxic risks currently understood and loosening the previous restrictive approach in patients with renal dysfunction.

Anion-templated synthesis of a switchable fluorescent [2]catenane with sulfate sensing capability.

Anion templation strategies have facilitated the synthesis of various catenane and rotaxane hosts capable of strong and selective binding of anions in competitive solvents. However, this approach has primarily relied on positively charged precursors, limiting the structural diversity and the range of potential applications of the anion-templated mechanically interlocked molecules. Here we demonstrate the synthesis of a rare electroneutral [2]catenane using a powerful, doubly charged sulfate template and a complementary diamidocarbazole-based hydrogen bonding precursor. Owing to the unique three-dimensional hydrogen bonding cavity and the embedded carbazole fluorophores, the resulting catenane receptor functions as a sensitive fluorescent turn-ON sensor for the highly hydrophilic sulfate, even in the presence of a large excess of water. Importantly, the [2]catenane exhibits enhanced binding affinity and selectivity for sulfate over its parent macrocycle and other acyclic diamidocarbazole-based receptors. We demonstrate also, for the first time, that the co-conformation of the catenane may be controlled by reversible acid/base induced protonation and deprotonation of the anionic template, SO42-. This approach pioneers a new strategy to induce molecular motion of interlocked components using switchable anionic templates.

A new perspective on vitamin B12 deficiency in rheumatology: a case-based review.

Vitamin B12 (cobalamin) deficiency is common in patients with rheumatic diseases. Pernicious anemia is a well-known cause, but recent reports suggest that autoimmune-derived deficiency may not be limited to this cause alone. Symptoms of low vitamin B12 concentration are often deceptive, mimicking and overlapping with symptoms of other conditions. Neuropsychiatric manifestations, anemia, and fatigue are frequently attributed to a rheumatic disease without further evaluation. In this study, we present three cases of patients with neuropathic pain, depression, fatigue, and muscle weakness, initially attributed to a rheumatic disease, which almost completely resolved after implementing vitamin B12 supplementation. Furthermore, we provide an overview of current scientific reports regarding the potential use of cobalamin in rheumatology. Treatment of pain and neuropathy, often very challenging in long-lasting rheumatic diseases, can be more effective after a course of vitamin B12, even when no apparent deficiency is detected in laboratory tests. Considering recent research demonstrating vitamin B12's nerve-protecting properties, we recommend that physicians should assess vitamin B12 levels early in the diagnostic process of rheumatic diseases. In specific cases, physicians should consider cobalamin supplementation regardless of vitamin B12 serum concentration.

Full-field in vivo experimental study of the strains of a breathing human abdominal wall with intra-abdominal pressure variation.

The presented study aims to assess the mechanical behaviour of the anterior abdominal wall based on an in vivo experiment on humans. Full-field measurement of abdominal wall displacement during changes of intra-abdominal pressure is performed using a digital image correlation (DIC) system. Continuous measurement in time enables the observation of changes in the strain field during breathing. The understanding of the mechanical behaviour of a living human abdominal wall is important for the proper design of surgical meshes used for ventral hernia repair, which was also a motivation for the research presented below. The research refers to the strain field of a loaded abdominal wall and presents the evolution of principal strains and their directions in the case of 12 subjects, 8 male and 4 female. Peritoneal dialysis procedure allows for the measurement of intra-abdominal pressure after fluid introduction. High variability among patients is observed, also in terms of principal strain direction. Subjects exhibit intra-abdominal pressure of values from 11 to 21 cmH2O. However, the strain values are not strongly correlated with the pressure value, indicating variability of material properties.

Vitamin B12 and a metal-organic framework enable the photocatalytic generation of alkyl radicals.

A versatile Co-catalyst-vitamin B12 (cobalamin)-can be photochemically reduced to its catalytically active Co(I) form under visible light irradiation, in the presence of MIL-125-NH2(Ti) as a photocatalyst and utilized for the generation of alkyl radicals. The prior reduction of cobalamin to the Co(II) form is not required in this method.

Impact of diet modification on body mass and kidney function in patients with diabetic nephropathy: a pilot study.

OBJECTIVES: The increasing trend in chronic kidney disease (CKD) has occurred in parallel with the increased prevalence of obesity and diabetes type 2. The relationship between a reduction in body mass and protein intake in diabetic nephropathy (DN) has not been adequately understood. This study aimed to determine whether dietary intervention in an adult with DN is associated with decreasing proteinuria or changes in kidney function over six months. METHODS: The study included 120 patients with DN, consecutively admitted to a dietitian from a Kidney Disease Clinic. Patients were classified into two groups: a reduction diet or a normal calorie diet, both with 0.8 g of protein/kg of ideal body weight/day. Anthropometric and laboratory assessments were done before and after observation. RESULTS: After six months, in the study group of patients on a reducing diet, a decrease in body mass, body mass index (BMI) and stabilization of estimated glomerular filtration rate (eGFR) were observed. There was also a significant correlation between the time of diabetes diagnosis and eGFR and creatinine (R Spearman=-0.24 and 0.3, respectively; p=0.05). There were no other significant associations between body mass, BMI, albuminuria, eGFR, or creatinine. CONCLUSIONS: The study shows that obesity is a common comorbid disease in patients with DN and that dietary intervention is associated with a significant reduction in body mass and stabilization of eGFR in these patients.

pH-Dependent transport of amino acids across lipid bilayers by simple monotopic anion carriers.

The transport of amino acids across lipid membranes is vital for the proper functioning of every living cell. In spite of that, examples of synthetic transporters that can facilitate amino acid transport are rare. This is mainly because at physiological conditions amino acids predominantly exist as highly polar zwitterions and proper shielding of their charged termini, which is necessary for fast diffusion across lipophilic membranes, requires complex and synthetically challenging heteroditopic receptors. Here we report the first simple monotopic anion receptor, dithioamide 1, that efficiently transports a variety of natural amino acids across lipid bilayers at physiological pH. Mechanistic studies revealed that the receptor rapidly transports deprotonated amino acids, even though at pH 7.4 these forms account for less than 3% of the total amino acid concentration. We also describe a new fluorescent assay for the selective measurement of the transport of deprotonated amino acids into liposomes. The new assay allowed us to study the pH-dependence of amino acid transport and elucidate the mechanism of transport by 1, as well as to explain its exceptionally high activity. With the newly developed assay we screened also four other representative examples of monotopic anion transporters, of which two showed promising activity. Our results imply that heteroditopic receptors are not necessary for achieving high amino acid transport activities and that many of the previously reported anionophores might be active amino acid transporters. Based on these findings, we propose a new strategy for the development of artificial amino acid transporters with improved properties.

Dissecting transmembrane bicarbonate transport by 1,8-di(thio)amidocarbazoles.

Synthetic ionophores able to transport bicarbonate and chloride anions across lipid bilayers are appealing for their wide range of potential biological applications. We have studied the bicarbonate and chloride transport by carbazoles with two amido/thioamido groups using a bicarbonate-sensitive europium(III) probe in liposomes and found a highly remarkable transporter concentration dependence. This can be explained by a combination of two distinct transport mechanisms: HCO3-/Cl- exchange and a combination of unassisted CO2 diffusion and HCl transport, of which the respective contributions were quantified. The compounds studied were found to be highly potent HCl transporters. Based on the mechanistic insights on anion transport, we have tested the antimicrobial activity of these compounds and found a good correlation with their ion transport properties and a high activity against Gram-positive bacteria.

Associations between Serum Saturated Fatty Acids Content and Mortality in Dialysis Patients.

Background: Cardiovascular mortality in dialysis population remains very high. Saturated fatty acids (SFA) contribute to atherosclerosis and to cardiovascular risk. Aim: The aim of this study was to evaluate the relationship between mortality in dialysis patients and the serum SFA content. Methods: Survival of 54 patients on dialysis was assessed. A total of 21 SFA from patients' sera were measured by gas chromatography-mass spectrometry (GC-MS). Diet was assessed by food frequency questionnaire FFQ-6. The SFA content is presented as fatty acid proportion (%). Results: During the observation time (median 66 months) 22 patients died. There was a significant relationship between elevated SFA (above SFA mean) and mortality (log-rank 3.13; p = 0.0017). Moreover, patients who ingested foods rich in SFA, according to FFQ-6, had a higher mortality risk (log-rank 2.24; p = 0.03). The hazard ratio for mortality associated with increased SFA content equalled 4.47 (1.63−12.26). Addition of age and inflammation (hsCRP > 5 mg/L) into the Cox model did not modify this relationship. However, SFA content turned out to be significantly higher in patients with diabetes mellitus and cardiovascular disease, as compared to patients free from these co-morbidities. Their addition to the model attenuated the relationship between SFA and mortality, making it statistically insignificant. Conclusion: The serum content of SFA turned out to be a strong predictor of mortality in dialysis patients. However, given the significant associations between SFA, DM, and CVD, interventional studies with controlled SFA intake are needed to evaluate the causal links between SFA, co-morbidities and survival.

A novel in vivo approach to assess strains of the human abdominal wall under known intraabdominal pressure.

The study concerns mechanical behaviour of a living human abdominal wall. A better mechanical understanding of a human abdominal wall and recognition of its material properties is required to find mechanically compatible surgical meshes to significantly improve the treatment of ventral hernias. A non-invasive methodology, based on in vivo optical measurements is proposed to determine strains of abdominal wall corresponding to a known intraabdominal pressure. The measurement is performed in the course of a standard procedure of peritoneal dialysis. A dedicated experimental stand is designed for the experiment. The photogrammetric technique is employed to recover the three-dimensional surface geometry of the anterior abdominal wall at the initial and terminal instants of the dialysis. This corresponds to two deformation states, before and after filling the abdominal cavity with dialysis fluid. The study provides information on strain fields of living human abdominal wall. The inquiry is aimed at principal strains and their directions, observed at the level from -10% to 17%. The intraabdominal pressure related to the amount of introduced dialysis fluid measured within the medical procedure covers the range 11-18.5 cmH2O. The methodology leads to the deformation state of the abdominal wall according to the corresponding loading conditions. Therefore, the study is a step towards an identification of mechanical properties of living human abdominal wall.

Carbazole-Based Colorimetric Anion Sensors.

Owing to their strong carbazole chromophore and fluorophore, as well as to their powerful and convergent hydrogen bond donors, 1,8-diaminocarbazoles are amongst the most attractive and synthetically versatile building blocks for the construction of anion receptors, sensors, and transporters. Aiming to develop carbazole-based colorimetric anion sensors, herein we describe the synthesis of 1,8-diaminocarbazoles substituted with strongly electron-withdrawing substituents, i.e., 3,6-dicyano and 3,6-dinitro. Both of these precursors were subsequently converted into model diamide receptors. Anion binding studies revealed that the new receptors exhibited significantly enhanced anion affinities, but also significantly increased acidities. We also found that rear substitution of 1,8-diamidocarbazole with two nitro groups shifted its absorption spectrum into the visible region and converted the receptor into a colorimetric anion sensor. The new sensor displayed vivid color and fluorescence changes upon addition of basic anions in wet dimethyl sulfoxide, but it was poorly selective; because of its enhanced acidity, the dominant receptor-anion interaction for most anions was proton transfer and, accordingly, similar changes in color were observed for all basic anions. The highly acidic and strongly binding receptors developed in this study may be applicable in organocatalysis or in pH-switchable anion transport through lipophilic membranes.

Boosting Anion Transport Activity of Diamidocarbazoles by Electron Withdrawing Substituents.

Artificial chloride transporters have been intensely investigated in view of their potential medicinal applications. Recently, we have established 1,8-diamidocarbazoles as a versatile platform for the development of active chloride carriers. In the present contribution, we investigate the influence of various electron-withdrawing substituents in positions 3 and 6 of the carbazole core on the chloride transport activity of these anionophores. Using lucigenin assay and large unilamellar vesicles as models, the 3,6-dicyano- and 3,6-dinitro- substituted receptors were found to be highly active and perfectly deliverable chloride transporters, with EC50,270s value as low as 22 nM for the Cl-/NO3 - exchange. Mechanistic studies revealed that diamidocarbazoles form 1:1 complexes with chloride in lipid bilayers and facilitate chloride/nitrate exchange by carrier mechanism. Furthermore, owing to its increased acidity, the 3,6-dinitro- substituted receptor acts as a pH-switchable transporter, with physiologically relevant apparent pKa of 6.4.

The Causes and Potential Injurious Effects of Elevated Serum Leptin Levels in Chronic Kidney Disease Patients.

Leptin is an adipokine that regulates appetite and body mass and has many other pleiotropic functions, including regulating kidney function. Increased evidence shows that chronic kidney disease (CKD) is associated with hyperleptinemia, but the reasons for this phenomenon are not fully understood. In this review, we focused on potential causes of hyperleptinemia in patients with CKD and the effects of elevated serum leptin levels on patient kidney function and cardiovascular risk. The available data indicate that the increased concentration of leptin in the blood of CKD patients may result from both decreased leptin elimination from the circulation by the kidneys (due to renal dysfunction) and increased leptin production by the adipose tissue. The overproduction of leptin by the adipose tissue could result from: (a) hyperinsulinemia; (b) chronic inflammation; and (c) significant lipid disturbances in CKD patients. Elevated leptin in CKD patients may further deteriorate kidney function and lead to increased cardiovascular risk.

Analysis of Serum Fatty Acids Profile in Kidney Transplant Recipients.

Patients with end-stage kidney disease, treated with renal transplantation, are at increased risk of cardio-vascular disease (CVD) and cardio-vascular mortality. They are also characterized by an atherogenic dyslipidemia. Alterations of the fatty acids (FA) profile contribute to increased cardio-vascular risk in the general population. In the current study, we test the hypothesis that kidney transplantation is associated with ab-normalities in FA profile. The FA profile was analyzed by gas chromatography-mass spectrometry in 198 renal transplant recipients, and 48 control subjects. The most profound differences between renal transplant patients and controls were related to the content of branched chain FA, monounsaturated FA, and n-6 polyunsaturated FA, respectively. The FA profile significantly separated the patients from the controls in the principal component analysis (PCA). The abnormalities of FA profile showed a tendency for normalization in long-term kidney recipients, as compared to patients with recent transplants. The n-3 PUFA content demonstrated a strong inverse association with the presence of inflammation. Most profound alterations of the FA profile were observed in patients with impaired graft function (glomerular filtration rate < 45 mL/min). The study demonstrated significant disorders of the FA profile in kidney transplant recipients, which might contribute to cardio-vascular risk in this vulnerable patient population.

Transmembrane anion transport promoted by thioamides.

Thioamide groups represent useful hydrogen-bonding motifs for the development of active transmembrane anion transporters. Using a 1,8-di(thioamido)carbazole scaffold the superior performance of thioamides compared with the parent amides has been demonstrated.

Disorders of Serum Polyunsaturated Fatty Acids in Renal Transplant Patients.

BACKGROUND: Disturbances in polyunsaturated fatty acids (PUFA) could predispose renal transplant (RTx) patients to cardiovascular risk. The purpose of this study was to evaluate serum content of ω-3 and ω-6 PUFA in RTx subjects, in comparison to nontransplanted chronic kidney disease (CKD) patients in predialysis stages and to healthy controls. In the second part of the study, PUFA were analyzed in subcutaneous adipose tissue of CKD subjects at the time of kidney transplantation. METHODS: The first part of the study was conducted in a cohort (n = 134) of 3 groups: patients after renal transplantation (RTx group, n = 24), patients with CKD in stages 2-5, not on dialysis (CKD-ND group, n = 67), and controls without CKD (control group, n = 43). The fatty acids (FA) assessed by gas chromatography-mass spectrometry (GC-MS) were alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), linoleic acid (LA), and arachidonic acid (AA). Diet was assessed by food frequency questionnaire FFQ-6. In the second part of the study, the same FA were evaluated in samples of adipose tissue taken during the kidney transplantation procedure and compared with FA of controls from the adipose tissue collected during hernia surgeries. RESULTS: The first part of the study showed that RTx patients presented significantly lower serum content of all the examined PUFA, in comparison to the CKD-ND group and controls. For instance, EPA in RTx equaled 0.65 ± 0.32%, in CKD-ND 0.82 ± 0.43%, and in controls 1.06 ± 0.68% (P = .005). No significant correlations were found between serum PUFA and diet in RTx patients. The second part of the study revealed no significant difference in the adipose tissue PUFA between CKD patients at the time of kidney transplantation and controls. CONCLUSIONS: RTx patients present with low serum content of potentially beneficial PUFA. This finding does not seem to be solely due to an altered diet. Observed disorders might result from immunosuppressive drugs or other, yet undetermined, causes.