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Background Previous studies showed that NK cells mediate contact hypersensitivity (CHS) reaction. Many reports are showing that obesity promotes several inflammatory diseases. It was shown that diet-induced obesity (DIO) aggravates classical T cell-mediated CHS in mice. Objectives To determine whether the high-fat diet (HFD) induced obesity modulates antigen-specific NK cell-mediated response. Methods We evaluated the effect of DIO on NK cell-mediated CHS reaction using a model of dinitrofluorobenzene (DNFB)-induced CHS in Rag1-/- mice. Results Rag1-/- mice fed HFD for 8 but not for 4 weeks developed aggravated CHS reaction determined by ear swelling measurement when compared to animals kept on normal diet (ND) prior to DNFB sensitization. The obese Rag1-/- mice presented the adipose tissue inflammation. Furthermore, in vitro analysis showed that feeding with HFD significantly increases IFN-γ and IL-12p70 and decreases adiponectin concentration in liver mononuclear cells (LMNC) culture supernatants. The flow cytometry analysis of LMNC revealed that HFD treatment prior to DNFB sensitization increases the percentage of NK1.1+ IFN-γ+ cell population and affects the development and maturation of NK1.1+ cells. Conclusions In summary, current results suggest that the DIO significantly modulates the local and systemic inflammatory response, contributing to exacerbation of the CHS response mediated by liver NK cells. This article is protected by copyright. All rights reserved.

Gastric ulcer bleeding in an AHA patient with persistent inhibitor can be effectively stopped with endoscopic methods of hemostasis and appropriate dosing of rFVIIa. In the event of recurrent bleed-ing episodes the treatment should be repeated several times, in or-der to minimize indications to surgical treatment as far as possible. Surgery in AHA patients with persistent inhibitor must be avoid-ed due to the risk of uncontrolled fatal bleeding; it should only be undertaken in immediately life-threatening situations.

The current case report presents a case of non‐thymoma‐associated exfoliative dermatitis in an 8‐year‐old European Shorthair female cat. The animal displayed extensive alopecia and excessive peeling of the epidermis. There were no other apparent disorders, except for the skin lesions. Roentgenographic and sonographic examinations, complete blood count and blood serum chemistry analyses, and skin biopsy were performed. The histopathological investigation revealed hyperkeratosis of the epidermis and the infiltration of lymphocytes and macrophages at the dermal‐epidermal junction around the hair follicles and sebaceous glands. Moreover, edema of the basal layer and melanin migration from the epidermis to the dermis were observed. The patient underwent treatment with immunosuppressive doses of prednisolone, antibiotic therapy, and baths in anti‐seborrheic shampoos and displayed resolution. However, recurrence was observed after one month. Consequently, the patient received cyclosporine A, in addition to the aforementioned treatment and the lesions resolved without relapse., A case of non‐thymoma‐associated exfoliative dermatitis has been reported in an 8‐year‐old European Shorthair female cat Histopathological investigation revealed hyperkeratosis of the epidermis and an infiltration of lymphocytes and macrophages at the border of the epidermis and dermis, around the hair follicles and sebaceous glands After two months of treatment with prednisolone and cyclosporine the lesions resolved without relapse.

Paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) is a recently detected syndrome whose criteria were first established in May 2020 (Royal College of Paediatrics and Child Health). The clinical course varies from mild to severe, life-threatening cases. This paper presents a case of an extremely severe course of PIMS with symptoms resembling Kawasaki syndrome in a previously healthy 13-year-old boy with obesity. A complication of the severe course of PIMS was the development of critical illness polyneuropathy in the patient.

Introduction Laparoscopic surgery is associated with several advantages. Surgical procedures in hemophilia or von Willebrand patients without replacement therapy (RT) to correct clotting factor deficiency may result in serious, life-threatening hemorrhagic episodes. Clotting factor concentrates improve hemostatic control but bleeding risk in major invasive procedures remains high. Aim Evaluation of totally extraperitoneal inguinal hernia repair (TEP-IHR) in patients with congenital hemorrhagic disorders (H) and comparison with results for non-hemophiliacs (NH) with regard to bleeding, postoperative pain, hernia recurrence, surgery time, demand for painkillers, hospital stay and recovery time. Material and methods The prospective controlled trial included 67 consecutive male patients scheduled for TEP-IHR between January 2010 and December 2018. Surgery was performed in groups H (n = 22) and NH (n = 45). Full study inclusion criteria were met by 65 patients (22 and 43 in H and NH groups respectively). Follow-up was carried out on the 1st, 2nd, and 7th day and in the 1st and 3rd month postoperatively. Results TEP-IHR was successful for all patients. No life-threatening bleeding occurred and no patient required red blood cell transfusions or reoperation. No hernia recurrence was reported. No statistically significant differences were observed between the groups with regard to surgery duration, postoperative hematoma frequency and demand for painkillers. In the H group, pain intensity was significantly higher during the first postoperative month and hospitalization and recovery were significantly longer. Conclusions TEP-IHR in hemophiliacs with RT is feasible and as effective for preventing hernia recurrence as in NH-patients. In hemophiliacs risk of bleeding complications and demand for painkillers are comparable to non-hemophiliacs although pain is more intense.

There is strong evidence that neuronal bases for language processing are remarkably similar for sign and spoken languages. However, as meanings and linguistic structures of sign languages are coded in movement and space and decoded through vision, differences are also present, predominantly in occipitotemporal and parietal areas, such as superior parietal lobule (SPL). Whether the involvement of SPL reflects domain-general visuospatial attention or processes specific to sign language comprehension remains an open question. Here we conducted two experiments to investigate the role of SPL and the laterality of its engagement in sign language lexical processing. First, using unique longitudinal and between-group designs we mapped brain responses to sign language in hearing late learners and deaf signers. Second, using transcranial magnetic stimulation (TMS) in both groups we tested the behavioural relevance of SPL’s engagement and its lateralisation during sign language comprehension. SPL activation in hearing participants was observed in the right hemisphere before and bilaterally after the sign language course. Additionally, after the course hearing learners exhibited greater activation in the occipital cortex and left SPL than deaf signers. TMS applied to the right SPL decreased accuracy in both hearing learners and deaf signers. Stimulation of the left SPL decreased accuracy only in hearing learners. Our results suggest that right SPL might be involved in visuospatial attention while left SPL might support phonological decoding of signs in non-proficient signers.

Study aim: Judo training leads to an increase in the muscle mass of athletes. The consequence of this is a high level of body mass index (BMI). At the same time, the body’s fat percentage is reduced. This phenomenon has been well-described in older age groups. However, body build and composition parameters of the youngest judokas are still unclear. The aim of the study was to answer the following questions: Do the training and recruitment of athletes influence body build and composition in the studied groups? Are BMI and body fat percentage differentiated between children and younger children? Are body build and composition in studied group related to competitive experience and level of achievement in competitions? Basic procedures: The study group consisted of 21 judokas aged 11 to 12 years (younger children) and 71 non-training peers, as well as18 judokas aged 13 to 14 years (children) and 44 of their non-training peers. Body mass and composition were determined using the Tanita TBF-551 body composition analyser. Examination of the judokas was conducted during regional championships. Results and main findings: In the younger age group, significantly higher BMI and body fat percentage were observed in the group of non-training peers (20.5 and 22.2%; in judokas: 18.2 and 17.6%, respectively). In children, significant differences were observed only in body fat percentage. Its value was lower in judokas and amounted to 16.2% (in non-athlete peers: 20.1%). Comparison of body build and composition between judo athletes in the examined age groups revealed significant differences in the case of BMI. The value of this index in children was 20.5, which was significantly higher than in the younger children (17.6). No correlations of body build and composition with competitive experience and level of achievement in competitions were found in the studied groups. Conclusions: A 4-year training experience is a significant factor in the development of judo-specific body build and composition. However, their indices are not related to the level of achievement in the youngest age groups.

A two- year-old Sphynx cat, an unneutered female with multiple erythematous papules with hyperpigmentation was presented. In skin biopsy, in the dermis, well differentiated monomorphic mast cells were found. Fungal culture was positive for Microsporum canis. Diagnosis of urticaria pigmentosa following M. canis infection was made. The animal was successfully treated with itraconazole orally and shampoo containing chlorhexidine and miconazole. To the authors’ knowledge, this is the first reported case of urticaria pigmentosa following the dermatophyte infection in a Sphynx cat.

BACKGROUND It has previously been shown that appropriate distribution of immune cells between different tissues and organs of the body is required for proper function of the immune system. Our previous work demonstrated that surgical trauma in mice induces γδT lymphocyte migration from peripheral blood to the peritoneal lymphoid organs. These described γδT cells have immunoregulatory activity as they suppress the cell-mediated immune response in vitro. We found a similar phenomenon in patients after different surgical operations. In the current study, we analyse post-operative complications in patients with a significant post-operative decrease in γδT cells. METHODS We investigated the percentage of γδT cells in peripheral blood of patients undergoing standard surgical procedures (gastric resection, colorectal resection, cholecystectomy and strumectomy) before and 3 days after the operation. The percentage of γδT cells was evaluated by the fluorescence-activated cell sorting cytofluorimeter. Patients were grouped based on the decrease of γδT cells. We compared the number of septic complications in patients with a large and small decrease in γδT cells. RESULTS After major surgery in the peritoneal cavity (gastric and colorectal surgery), in the group that had a large decrease in γδT cells we found significantly more septic complications than in the group of patients with small γδT decrease. That effect was not visible after less traumatic surgery. CONCLUSION Surgery results in a decreased percentage of γδT lymphocytes in the peripheral human blood which correlates with the number of septic complications. This observation may help to predict post-operative recovery after gastroabdominal surgery.

Methylglyoxal (MGO) is an endogenous toxin, mainly produced as a by-product of glycolysis that has been associated to aging, Alzheimer’s disease, and inflammation. Cell culture studies reported that MGO could impair the glyoxalase, thioredoxin, and glutathione systems. Thus, we investigated the effect of in vivo MGO administration on these systems, but no major changes were observed in the glyoxalase, thioredoxin, and glutathione systems, as evaluated in the prefrontal cortex and the hippocampus of mice. A previous study from our group indicated that MGO administration produced learning/memory deficits and depression-like behavior. Confirming these findings, the tail suspension test indicated that MGO treatment for 7 days leads to depression-like behavior in three different mice strains. MGO treatment for 12 days induced working memory impairment, as evaluated in the Y maze spontaneous alternation test, which was paralleled by low dopamine and serotonin levels in the cerebral cortex. Increased DARPP32 Thr75/Thr34 phosphorylation ratio was observed, suggesting a suppression of phosphatase 1 inhibition, which may be involved in behavioral responses to MGO. Co-treatment with a dopamine/noradrenaline reuptake inhibitor (bupropion, 10 mg/kg, p.o.) reversed the depression-like behavior and working memory impairment and restored the serotonin and dopamine levels in the cerebral cortex. Overall, the cerebral cortex monoaminergic system appears to be a preferential target of MGO toxicity, a new potential therapeutic target that remains to be addressed.

Recent evidence suggests that young rodents submitted to high fructose (FRU) diet develop metabolic, and cognitive dysfunctions. However, it remains unclear whether these detrimental effects of FRU intake can also be observed in middle-aged mice. Nine months-old C57BL/6 female mice were fed with water (Control) or 10% FRU in drinking water during 12 weeks. After that, metabolic, and neurochemical alterations were evaluated, focusing on neurotransmitters, and antioxidant defenses. Behavioral parameters related to motor activity, memory, anxiety, and depression were also evaluated. Mice consuming FRU diet displayed increased water, and caloric intake, resulting in weight gain, which was partially compensated due to decreased food pellet intake. FRU fed animals displayed increased plasma glucose, and cholesterol levels, which was not observed in overnight-fasted animals. Superoxide dismutase (SOD), and catalase (CAT) activities were markedly decreased in the prefrontal cortex of animals receiving FRU diet, while glutathione peroxidase (GPx) slightly increased. Liver (lower GPx), striatum (higher SOD and lower CAT), and hippocampus (no changes) were less impacted. No changes were observed in glutathione reductase, and thioredoxin reductase activities, two ancillary enzymes for peroxide detoxification. FRU intake did not alter serotonin, dopamine, and norepinephrine levels in the hippocampus, prefrontal cortex, and striatum. No significant alterations were observed in working, and short-term spatial memory; and in anxiety- and depressive-like behaviors in animals treated with FRU. Increased locomotor activity was observed in FRU-fed middle-aged mice, as evaluated in the open field, elevated plus-maze, Y maze, and object location tasks. Overall, these results demonstrate that high FRU consumption can disturb antioxidant defenses, and increase locomotor activity in middle-aged mice, open the opportunity for further studies to address the underlying mechanisms related to these findings.

Type 2 diabetes mellitus (T2DM) is a major cause of morbidity and mortality worldwide and is an important public health issue. A significant proportion of insulin-treated patients with T2DM do not reach target glycated haemoglobin (HbA1c) values, which ultimately increases their risk of long-term microvascular and macrovascular complications. One potential option to improve diabetes control in these patients may be the use of new insulin formulations including second-generation basal insulin analogues such as insulin glargine 300 U/mL (Gla-300). Several published randomised controlled trials have assessed the clinical effectiveness of Gla-300, mostly versus insulin glargine 100 U/mL as well as insulin degludec. However, there is limited information about the real-world effectiveness of Gla-300 when patients are transitioned directly from neutral protamine Hagedorn (NPH) human basal insulin. The primary objective of this study was to evaluate the effectiveness of Gla-300, defined as the percentage of participants with an HbA1c reduction of ≥0.5%, 6 months after switching from NPH insulin, in participants with T2DM. Secondary objectives included the safety assessment based on the percentage of patients experiencing ≥1 episodes and the number of hypoglycaemic episodes by category: severe, symptomatic, symptomatic confirmed, diurnal or nocturnal, change in body weight, and insulin dose. A total of 469 participants completed the 6-month observation period. Mean baseline HbA1c was 9.19%. The percentage of participants with a ≥0.5% improvement in HbA1c from baseline was 71.7% at 6 months. Mean HbA1c decreased at 3 and 6 months by 0.77% (±0.98) and 1.01% (±1.12), respectively (p<0.00001 versus baseline), while fasting glycaemia decreased by 32 mg/dL and 37 mg/dL, respectively (p<0.00001 versus baseline). There were moderate increases in the doses of both Gla-300 and, if used, short-acting insulins during the 6 months of observation. The percentage of participants with ≥1 hypoglycaemia event during the preceding 4 weeks decreased significantly from baseline to 3 and 6 months, as did the proportion with symptomatic hypoglycaemia at night (p<0.00001 versus baseline). No participants had severe hypoglycaemia after a switch to Gla-300. Body mass, waist and hip circumferences, and waist : hip ratio did not change significantly. In conclusion, this large, prospective, observational study demonstrated that switching from NPH insulin to Gla-300 resulted in a significant improvement in HbA1c, with only a moderate increase in insulin dose, a decreased risk of hypoglycaemia, and no increase in body weight.

Introduction The use of implants in inguinal hernia repair has reduced its recurrence rate. However, postoperative groin pain still remains an unresolved problem. There are suggestions that in totally extraperitoneal inguinal hernia repair (TEP-IHR) two of the likely factors responsible for pain are use of fixation and the type of fixation used. Aim To evaluate the impact of mesh fixation on the incidence of postoperative pain, restriction of physical activities, hernia recurrence risk, return to normal activities and demand for analgesics in patients after unilateral TEP-IHR. Material and methods Unilateral TEP-IHR was performed in 139 male patients randomized to three groups: self-gripping mesh (SG), lightweight mesh (L) and lightweight mesh with fixation (LF). Full study-inclusion criteria were met by 110 patients; 43, 18 and 49 in groups SG, L and LF respectively. Follow-up occurred on the 1st, 2nd, and 7th day and 3, 6, 12 months postoperatively. The numeric rating scale (NRS) was used to assess pain and the EuraHS-QoL (European Registry for Abdominal Wall Hernias Quality of Life Score) questionnaire to compare quality of life (QoL) prior to surgery and one year later. Results No statistically significant differences were observed between study groups with regard to the incidence rate and intensity of acute post-operative pain, chronic pain, analgesic demand, return to normal activity, hernia recurrence rate and post-operative QoL. Conclusions Lack of fixation in TEP-IHR does not increase the risk of hernia recurrence, and its presence does not significantly worsen the treatment results; especially it does not increase the incidence of chronic pain.

Introduction Cystic fibrosis (CF) involves chronic inflammation and decreased pulmonary function, which increase caloric demand. Yet, sufficient energy provision is hindered by reduced appetite and fat malabsorption. Brain-derived neurotrophic factor (BDNF), leptin, and neuropeptide Y (NPY) belong to energy balance-regulating factors. We aimed to assess their concentrations in CF patients in order to search for potential clinical correlates. Material and methods This was an exploratory, cross-sectional study. Patients' weight and height Z-scores, forced expiratory volume in 1 s (FEV1%), exocrine pancreatic status (fecal elastase-1), genotypes, and other characteristics were assessed. Serum concentrations of BDNF, leptin, NPY, IL-6, and TNF-α were measured using ELISA. Results The study enrolled 56 patients, of whom 29 (52%) were female and 17 (30%) were younger than 16 years. Median (1st-3rd quartile) mass Z-score was -0.85 (-1.56-(-0.36)); median FEV1 was 70.5% (45.0-89.5); 48 (86%) patients had exocrine pancreatic insufficiency and 8 (14%) diabetes. Overall, median concentrations were: BDNF: 33.91 ng/ml (26.40-40.43), leptin: 12.05 ng/ml (8.93-17.77), NPY: 2.86 ng/ml (1.75-4.42). None of these factors correlated with mass Z-score, FEV1%, IL-6 or TNF-α. Leptin and NPY correlated negatively (ρ = -0.62, p = 3 × 10-7); BDNF/NPY ratio was associated with leptin (ρ = 0.54, p = 2 × 10-5), BDNF/leptin ratio correlated with NPY (ρ = 0.60, p = 1 × 10-6). In a multivariable regression analysis NPY was weakly, but independently, associated with FEV1%, and leptin with age. Conclusions BDNF and leptin were not associated with weight Z-score or FEV1%. Serum NPY concentrations seemed to be lower in CF patients with reduced pulmonary function independently of malnutrition and inflammation.

Methylglyoxal (MGO) is a highly reactive dicarbonyl molecule that promotes the formation of advanced glycation end products (AGEs), which are believed to play a key role in a number of pathologies, such as diabetes, Alzheimer's disease, and inflammation. Here, Swiss mice were treated with MGO by intraperitoneal injection to investigate its effects on motor activity, mood, and cognition. Acute MGO treatment heavily decreased locomotor activity in the open field test at higher doses (80-200 mg/kg), an effect not observed at lower doses (10-50 mg/kg). Several alterations were observed 4 h after a single MGO injection (10-50 mg/kg): (a) plasma MGO levels were increased, (b) memory was impaired (object location task), (c) anxiolytic behavior was observed in the open field and marble burying test, and (d) depressive-like behavior was evidenced as evaluated by the tail suspension test. Biochemical alterations in the glutathione and glyoxalase systems were not observed 4 h after MGO treatment. Mice were also treated daily with MGO at 0, 10, 25 and 50 mg/kg for 11 days. From the 5th to the 11th day, several behavioral end points were evaluated, resulting in: (a) absence of motor impairment as evaluated in the open field, horizontal bars and pole test, (b) depressive-like behavior observed in the tail suspension test, and (c) cognitive impairments detected on working, short- and long-term memory when mice were tested in the Y-maze spontaneous alternation, object location and recognition tests, and step-down inhibitory avoidance task. An interesting finding was a marked decrease in dopamine levels in the prefrontal cortex of mice treated with 50 mg/kg MGO for 11 days, along with a ~ 25% decrease in the Glo1 content. The MGO-induced dopamine depletion in the prefrontal cortex may be related to the observed memory deficits and depressive-like behavior, an interesting topic to be further studied as a potentially novel route for MGO toxicity.

Background: To assess the reliability of complete blood count (CBC) in the capillary blood of children with acute gastroenteritis (AGE), with a focus on leukocytes.Methods: This was a retrospective cross-sectional study. Complete blood count was compared between the capillary and venous blood in children admitted to a pediatric gastroenterology department with primary diagnosis of AGE (ICD-10 A09, A08.0, A08.2). Capillary blood was obtained in the emergency room and venous blood was sampled in the ward shortly thereafter during peripheral intravenous line placement.Results: One hundred and forty children were included. The mean (±SD) age and weight of patients were 3.0 ± 2.9 years and 16 ± 9 kg; 26% had leukocytosis. The mean difference between obtaining results of capillary and venous blood tests was 2 ± 1 h. Area under the receiver operating characteristic curve (AUC) for the identification of leukocytosis using the capillary blood was 0.98 (95% CI 0.96–1.0). The sensitivity and specificity were 86 and 98%, respectively (accuracy 95%). The positive and negative predictive values were 94 and 95%, respectively. The intraclass correlation coefficient revealed high concordance between capillary and venous CBC measurements (leukocyte count 0.94, hemoglobin 0.88, erythrocyte count 0.77, hematocrit 0.79, platelet count 0.90). Matched pairs comparisons revealed marginally higher erythrocytes (difference of medians: 0.2 T/L), hemoglobin (0.3 g/dL), hematocrit (1.0%), and platelets (9 G/L) in the capillary blood.Conclusion: Capillary CBC is useful in detecting leukocytosis in children with AGE.

BACKGROUND: Previous studies showed that liver NK cells mediate contact hypersensitivity (CHS) reaction in mice. There are many reports showing that obesity is accompanied with chronic low-grade inflammation and it promotes several inflammatory diseases. It was shown that diet-induced obesity (DIO) aggravates classical T cell-mediated CHS in C57BL/6 mice. Our work sheds light on a poorly explored subject of the influence of DIO on the course of NK cell-mediated CHS reaction in mice. METHODS: We evaluated the effect of DIO on NK cell-mediated CHS reaction using a model of dinitrofluorobenzene (DNFB)-induced CHS in Rag1-/- mice. RESULTS: Our data show that mice fed HFD for 8 but not for 4 weeks developed aggravated CHS reaction determined by ear swelling measurement when compared to animals kept on normal diet (ND) prior to DNFB sensitization. The obese Rag1-/- mice presented the adipose tissue inflammation. Furthermore, in vitro analysis showed that feeding with HFD significantly increases IFN-γ and IL-12p70 and decreases adiponectin concentration in liver mononuclear cells (LMNC) culture supernatants. The flow cytometry analysis of LMNC revealed that HFD treatment prior to DNFB sensitization increases the percentage of NK1.1+IFN-γ+ cell population and affects development and maturation of NK1.1+ cells. CONCLUSION: In summary, current results suggest that the DIO significantly modulates the local and systemic inflammatory response, contributing to exacerbation of the CHS response mediated by liver NK cells.

Introduction: Congenital factor VII deficiency is a rare hemorrhagic disorder inherited in an autosomal recessive pattern. Surgical treatment with insufficient diathesis correction is burdened with high risk of bleeding complications. The aim of the study was evaluation of the surgical outcome in patients with congenital factor VII deficiency and assessment of the efficacy and safety of recombinant activated factor VII (rFVIIa) used for perioperative hemostatic coverage in our two schemas of substitutive therapy. Material and methods: In the years 2002-2017 a total of 22 patients with congenital factor VII deficiency were subjected to surgery. Substitution therapy relied on rFVIIa used in two schemas. One involved 15 patients with factor VII activity of

Rising expenditures threaten healthcare sustainability. While transplant programs are typically considered profitable, transplant medications are expensive and frequently targeted for cost savings. This review aims to summarize available literature supporting cost-containment strategies used in solid organ transplant. Despite widespread use of these tactics, we found the available evidence to be fairly low quality. Strategies mainly focus on induction, particularly rabbit antithymocyte globulin (rATG), given its significant cost and the lack of consensus surrounding dosing. While there is higher-quality evidence for high single-dose rATG, and dose-rounding protocols to reduce waste are likely low risk, more aggressive strategies, such as dosing rATG by CD3+ target-attainment or on ideal-body-weight, have less robust support and did not always attain similar efficacy outcomes. Extrapolation of induction dosing strategies to rejection treatment is not supported by any currently available literature. Cost-saving strategies for supportive therapies, such as IVIG and rituximab also have minimal literature support. Deferral of high-cost agents to the outpatient arena is associated with minimal risk and increases reimbursement, although may increase complexity and cost-burden for patients and infusion centers. The available evidence highlights the need for evaluation of unique patient-specific clinical scenarios and optimization of therapies, rather than simple blanket application of cost-saving initiatives in the transplant population.

Background Studies on short-course preoperative radiotherapy in combination with total mesorectal excision for rectal cancer reported improved local control without clear survival benefits. The optimal fractionation and interval between radiotherapy and surgery are still under debate. We, therefore, aimed to report 10-year results of a randomized clinical trial (RCT, NCT01444495) comparing different time intervals between irradiation and surgery for rectal cancer. Material and methods Data from the RCT conducted at a single academic centre were reviewed based on regular control visits with the median follow-up of 12 years. Patients with rectal cancer were randomly assigned to short-course preoperative radiotherapy (5 × 5 Gy) followed by surgery 7–10 days (short interval) or 4–5 weeks (long interval) after the end of irradiation. The primary endpoint was the local recurrence rate at 5 years. The secondary endpoints included overall survival, disease-free survival, systemic recurrence rate, and downstaging. Results A total of 154 patients were randomly assigned to short (n = 77) or long interval (n = 77) surgery. The cumulative incidence of local recurrence at 10 years was 1.3% and 11.7% in the short and long-interval groups, respectively (p = 0.031). Accordingly, the incidence of systemic relapse was 14.3% versus 9.1% (p = 0.0319). There were no differences in the overall 10-year survival between patients subject to short and long-interval surgery (58% vs 61%, p = 0.754). However, patients with downstaging after radiotherapy had significantly better 10-year survival rates than non-responders. Conclusions Short-course preoperative radiotherapy with delayed surgery demonstrated an increased risk of local relapse over a 10-year follow-up.

Diffuse cutaneous mastocytosis was diagnosed in a 6-year-old, indoor, neutered female domestic European shorthair cat. Marked pruritus located mainly on the head and neck was noticed in the cat and in this area the animal had developed alopecia, crusts, and plaques. Histologically, monomorphic mast cells were found in the superficial dermis and around the hair follicles. Mast cells were well differentiated, with central nuclei and granular cytoplasm, with metachromatic granules which stained positively with Toluidine blue stain. The animal was successfully treated with oclacitinib at a dose of 1 mg/kg, twice a day per os.

Copeptin was found to be a stable biomarker of inflammation and stress response in cardiac, renal, metabolic, and respiratory conditions such as pneumonia. The aim of this study was to investigate the copeptin levels in biological fluids (serum and sputum supernatant) of cystic fibrosis pediatric patients during pulmonary exacerbation and remission and to investigate the possible influence of copeptin levels on disease severity and quality of life. Copeptin serum concentrations were measured in 28 pediatric cystic fibrosis (CF) patients: 13 in stable condition and 15 during pulmonary exacerbation. In 10 CF patients, copeptin was also measured in the sputum. In all the patients, we assessed complete blood count, BMI, sputum culture, lung function, and chest imaging (with Brasfield score). The severity of symptoms was assessed using the Shwachman-Kulczycki (SK) score, and the quality of life was assessed with the Cystic Fibrosis Quality of Life Questionnaire-Revised (CFQ-R). Copeptin concentrations in serum and sputum supernatant was measured using an ELISA kit. Statistical analysis was done in Statistica v.12. Serum and sputum copeptin levels were higher in CF patients during pulmonary exacerbation than in a stable period, but the differences were not significant (p=0.58 and p=0.13, respectively). Copeptin did not correlate significantly with any clinical, laboratory, or spirometry markers of exacerbation. There was, however, a significant inverse correlation between the serum copeptin level and symptoms severity (r=‐0.77, p=0.008) and radiological changes (r=‐0.5626, p=0.036) during pulmonary exacerbation in pediatric CF patients. Copeptin also inversely correlated with the quality of life domains in CF patients: vitality and eating habits, mostly loss of appetite (p=0.031 and p=0.016, respectively). Copeptin may be useful to identify patients with a higher risk of deterioration to improve their outcomes.

Background In the search for novel treatments for depression, ketamine has emerged as a unique agent with rapid antidepressant effects. Experimental tasks involving emotional processing can be used during functional magnetic resonance imaging scanning to investigate ketamine’s effects on brain function in major depressive disorder (MDD). This study examined ketamine’s effects on functional magnetic resonance imaging activity during an emotional processing task. Methods A total of 33 individuals with treatment-resistant MDD and 24 healthy control participants (HCs) took part in this double-blind, placebo-controlled crossover study. Participants received ketamine and placebo infusions 2 weeks apart, and functional magnetic resonance imaging scans were conducted at baseline and 2 days after each infusion. Blood oxygen level–dependent signal was measured during an emotional processing task, and a linear mixed-effects model was used to analyze differences in activation among group, drug, and task-specific factors. Results A group-by-drug interaction was observed in several brain regions, including a right frontal cluster extending into the anterior cingulate cortex and insula. Participants with MDD had greater activity than HCs after placebo infusion but showed lower activity after ketamine infusion, which was similar to the activity in HCs after placebo. A group-by-drug-by-task condition interaction was also found, which showed further differences that varied between implicit and explicit emotional conditions. Conclusions The main results indicate that ketamine had differential effects on brain activity in participants with MDD versus HCs. The pattern of activation in participants with MDD after ketamine infusion resembled the activation in HCs after placebo infusion, suggesting a normalization of function during emotional processing. The findings contribute to a better understanding of ketamine’s actions in the brain.

Background The interest in cystic fibrosis (CF) dyslipidaemia as a potential risk factor for cardiovascular disease is increasing with patients' survival. This study aimed to investigate CF dyslipidaemia, its clinical correlates and links to oxidized low-density lipoprotein (oxLDL), adiponectin, and apolipoprotein E (APOE). Methods This cross-sectional study assessed clinical characteristics of CF, as well as the serum lipid profile, oxLDL, adiponectin, and APOE. Results In total, 108 CF subjects were enrolled in this study, with a median age of 22 years, BMI of 20.5 kg/m2, FEV1% of 61%, of which 81% were pancreatic insufficient (PI). Healthy subjects (HS; n = 51) were in similar age. Hypocholesterolaemia occurred in 31% of CF subjects and in no HS. Hypertriglyceridaemia concerned 21% of patients (HS: 8%, p = .04), and low HDL-C 45% (HS: 6%, p Conclusions CF dyslipidaemia is highly prevalent and heterogenous. The lipid profile weakly associates with the clinical characteristics of CF as well as oxLDL, adiponectin, and APOE. Further research is needed, especially regarding HDL function in CF, the causes of hypertriglyceridaemia, and the value of essential fatty acid supplementation for CF dyslipidaemia.

Increased variability in spatiotemporal variables has been demonstrated in individuals after stroke. Gait Variability Index (GVI) has recently been proposed, potentially to be used as a standardized tool for quantifying gait impairment due to spatiotemporal variables. The experience with the GVI in patients after stroke is unknown.The aim of this study was to investigate the validity of the GVI as an outcome measure of gait disturbance after stroke.50 individuals (mean age 60.9 ± 11.2 years) after stroke at a chronic phase of recovery were included. The control group comprised 50 healthy subjects without gait disorders, matched for age and gender. Data on functional mobility and spatiotemporal gait parameters (BTS Smart system) was collected.The results showed lower mean GVI (mGVI) scores (mean 78.53 ± 6.12), lower GVI for the affected leg (mean 76.32 ± 7.98) and for the unaffected leg (mean 80.74 ± 4.68) in the individuals after stroke compared to the healthy subjects (mean 98.00 ± 6.32). This was significantly different from the control group mean for both mGVI, affected and unaffected leg - p 0.001. The GVI for the affected leg and unaffected leg as well as the mGVI were significantly correlated with all clinical measures of functional mobility (0.7≤R|0.9, 0.5≤|R|0.7, p 0.001).The validity of the GVI appears to be confirmed for individuals after stroke at a chronic stage of recovery. The GVI is lower in individuals after stroke compared to healthy controls. The GVI showed moderate to strong correlations with validated clinical measures of functional mobility. Application of the GVI in the clinical practice will significantly facilitate assessment of gait in individuals after stroke, in comparison to the necessity to interpret a large number of data from 3-dimensional gait analysis.Data are parts of the following clinical trial: ACTRN12617000436370 (anzctr.org.au).

OBJECTIVES Data on pancreatic exocrine secretion in the youngest children are scarce. The aim of the study was to determine the range of normal values for fecal fat concentration (FFC) and fecal fat excretion (FFE) in infants and toddlers up to 2 years of age. METHODS A total of 160 subjects aged 1 to 24 months (8 groups of 20: aged 1-3, 4-6 months, etc) were included in the study. In all children, FFC (%) and FFE (g/day) were assessed in 3-day stool collection. RESULTS FFC correlated with age (r = -0.50, P

The action of fractional lasers is based on the principle of fractional photothermolysis, which consists in generating in the skin a mesh of microthermal treatment zones surrounded by healthy, undamaged tissue. The most important factors determining the effectiveness of the procedure and the risk of developing adverse effects are: depth, size and density of microthermal treatment zones. The laser beam energy set by the operator is responsible for the depth of microthermal treatment zones penetration into the skin. The amount of intact, healthy tissue remaining between the micro damage zones and their depth depends on the number of laser beam passes. This draws attention to the need for careful selection of treatment parameters, which can only be performed by a person with appropriate qualifications. Fractional laser treatments are an effective form of therapy for many skin diseases and they have a low risk of side effects, most of which are short-term and harmless.

Introduction Methimazole-induced hypothyroidism is a clinical problem in the treatment of hyperthyroidism in people and animals and is an example of metabolic disease that can lead to fertility disorders and can give elastographic testicular changes. Material and Methods Ultrasound elastography using the Esaote MyLab Twice ultrasound system and a morphological examination of testes were performed in seven methimazole-administered (group E) and seven healthy rats (group C). Results The elasticity ratio of strains in the scrotal wall of the near-field test area to testicular tissue (ELX-T-RAT) and hardness percentage of strained tissues in the defined area of a testicle (ELX-T%HRD) in group E were statistically significantly lower than in group C. The degree of spermatogenesis was statistically significantly higher in group E than in group C and similarly seminiferous tubule diameters in group E were statistically significantly higher than in group C. Body weight and testicular weight in group E were statistically significantly lower than in group C. Conclusion Changes in the elastographical parameters of testes may result from disorders secondary to hypothyroidism. The usefulness of elastography is noteworthy in the case of evaluation of testis function in patients with some metabolic disorders.

This pre-specified analysis of DAPA-CKD assessed the impact of sodium-glucose cotransporter 2 inhibition on abrupt declines in kidney function in high-risk patients based on having chronic kidney disease (CKD) and substantial albuminuria. DAPA-CKD was a randomized, double-blind, placebo-controlled trial that had a median follow-up of 2.4 years. Adults with CKD (urinary albumin-to-creatinine ratio 200-5000 mg/g and estimated glomerular filtration rate 25-75 mL/min/1.73m2) were randomized to dapagliflozin 10 mg/day matched to placebo (2152 individuals each). An abrupt decline in kidney function was defined as a pre-specified endpoint of doubling of serum creatinine between two subsequent study visits. We also assessed a post-hoc analysis of investigator-reported acute kidney injury-related serious adverse events. Doubling of serum creatinine between two subsequent visits (median time-interval 100 days) occurred in 63 (2.9%) and 91 (4.2%) participants in the dapagliflozin and placebo groups, respectively (hazard ratio 0.68 [95% confidence interval 0.49, 0.94]). Accounting for the competing risk of mortality did not alter our findings. There was no heterogeneity in the effect of dapagliflozin on abrupt declines in kidney function based on baseline subgroups. Acute kidney injury-related serious adverse events were not significantly different and occurred in 52 (2.5%) and 69 (3.2%) participants in the dapagliflozin and placebo groups, respectively (0.77 [0.54, 1.10]). Thus, in patients with CKD and substantial albuminuria, dapagliflozin reduced the risk of abrupt declines in kidney function. HJLH and DC are co-primary authors. The DAPA-CKD Trial Committees and Investigators are listed in the Appendix.

Exertional rhabdomyolysis (ER) is an uncommon condition with a paucity of evidence-based guidance for diagnosis, management, and return to duty or play. Recently, a clinical practice guideline for diagnosis and management of ER in warfighters was updated by a team of military and civilian physicians and researchers using current scientific literature and decades of experience within the military population. The revision concentrated on challenging and controversial clinical questions with applicability to providers in the military and those in the greater sports medicine community. Specific topics addressed: 1) diagnostic criteria for ER; 2) clinical decision making for outpatient versus inpatient treatment; 3) optimal strategies for inpatient management; 4) discharge criteria; 5) identification and assessment of warfighters/athletes at risk for recurrent ER; 6) an appropriate rehabilitative plan; and finally, 7) key clinical questions warranting future research.

Background Conformal radiotherapy is a primary treatment in head and neck cancer, which putative adverse effects depend on relatively low doses of radiation delivered to increased volumes of normal tissues. Systemic effects of such treatment include radiation-induced changes in serum lipid profile, yet dose- and volume-dependence of these changes remain to be established. Methods Here we analyzed levels of choline-containing phospholipids in serum samples collected consecutively during the radiotherapy used as the only treatment modality. The liquid chromatography–mass spectrometry (LC-MS) approach applied in the study enabled the detection and quantitation of 151 phospholipids, including (lyso)phosphatidylcholines and sphingomyelins. Results No statistically significant differences were found in the pretreatment samples from patients with different locations and stages of cancer. To compensate for potential differences between schemes of radiotherapy, the biologically effective doses were calculated and used in the search of correlations with specific lipid levels. We found that the levels of several phospholipids depended on the maximum dose delivered to the gross tumor volume and total radiation energy absorbed by the patient’s body. Increased doses correlated with increased levels of sphingomyelins and reduced levels of phosphatidylcholines. Furthermore, we observed several phospholipids whose serum levels correlated with the degree of acute radiation toxicity. Conclusion Noteworthy, serum phospholipid levels were associated mainly with volumes of normal tissues irradiated with relatively low doses (i.e., total accumulated dose 20 Gy), which indicated the importance of such effects on the systemic response of the patient’s organism to intensity-modulated radiotherapy (IMRT).

Introduction. Insulin glargine 100 U/ml (Gla-100) is a long-lasting basal insulin analog injected once daily. This real-life study aimed to evaluate the efficacy and safety of Gla-100 in patients with type 1 (T1DM) and type 2 diabetes mellitus (T2DM), who were recently switched from isophane (NPH) insulin. Methods. This multicenter, prospective, 52-week observational study included 321 patients with T1DM and 766 with T2DM. The primary endpoint was the percentage of participants with a HbA 1c reduction of ≥ 0.5% at 52 weeks. The secondary endpoints included fasting plasma glucose (FPG) and HbA1c reduction over time, and hypoglycemic events. Results. Of the 1,087 patients included, 69.9% achieved the primary endpoint, while the mean HbA 1c decreased by 1.03% and the mean FPG by 31.8 mg/dL at 52 weeks. The average annual rate of severe hypoglycemia was 0.017 events per patient-year and 0.82 events per patient-year for nocturnal hypoglycemia. The proportion of participants experiencing severe diurnal or nocturnal hypoglycemia was significantly lower in the four weeks prior to the study end than the four weeks before the switch from NPH insulin (p

No gold standard is available to evaluate subjective psychophysical experiences in pediatric inflammatory bowel disease (IBD). We aimed to assess pain, anxiety, and limitations in social activities at diagnosis and the worst flare of the disease in relation to clinical expression, treatment and IBD severity. A total of 376 children completed the survey (Crohn&rsquo, s disease (CD) n = 196, ulcerative colitis (UC) n = 180). The questionnaire included 12 questions regarding pain, anxiety, and social activity, all assessed at recruitment and retrospectively at diagnosis and worst flare using a numeric rating scale. Patients that had ever been treated with systemic glucocorticosteroids scored higher in pain (p &lt, 0.001), anxiety (p = 0.015), and social activity domains (p &lt, 0.016) at worst flare, and the answers correlated with the number of steroid courses (p &lt, 0.0392). The perception of social activity limitations also correlated independently with the number of immunosuppressants (p &lt, 0.0433) and biological agents (p &lt, 0.0494). There was no difference in retrospective perception of pain, anxiety and social activity limitations between CD and UC patients at diagnosis and the worst flare. The level of limitations in social activity correlated with hospitalisations due to relapse, days spent in the hospital, number of relapses, and severe relapses with the strongest association of rho = 0.39 (p = 0.0004). Subjective and retrospective perception of pain, anxiety, and limitations in social activity differs depending on therapy, correlates with treatment modalities, and severity measures such as hospitalisations.

This study was to investigate whether the clinical course of inflammatory bowel disease (IBD) in a Polish paediatric cohort fits a seasonal pattern and depends on insolation. Two hundred and fourteen patients diagnosed with Crohn&rsquo, s disease (CD) and 192 with ulcerative colitis (UC) aged from 3 to 18 years, were recruited in seven centres of similar latitude. The seasons were defined as winter (December&ndash, February), spring (March&ndash, May), summer (June&ndash, August), autumn (September&ndash, November). The year was also divided depending on insolation threshold (3.0 kWh/m2/day). Patients diagnosed with IBD when the isolation was &gt, 3 kWh/m2/day had poorer nutritional status than those diagnosed while insolation was below threshold (lower standardised BMI at diagnosis (&minus, 0.81 ([&minus, 1.34]&ndash, [&minus, 0.03]) vs. &minus, 0.52 ([&minus, 1.15]&ndash, 0.15), p = 0.0320) and worst flare (&minus, 0.93 ([&minus, 1.37]&ndash, 0.05]) vs. &minus, 0.66 ([&minus, 1.23]&ndash, 0.17), p = 0.0344), with the need for more frequent biological treatment (45.5% vs. 32.7%, p = 0.0100). Patients diagnosed in winter were significantly younger at diagnosis (11.4 vs. 13.0, padj = 0.0180) and first immunosuppressive treatment (11.3 vs. 13.3, padj = 0.0109) than those diagnosed in other seasons. CD patients diagnosed in months with higher insolation spent more days in hospital than those diagnosed in months with lower insolation [4.6 (1.8&ndash, 11.8) vs. 2.9 (1.3&ndash, 6.2), p = 0.0482]. CD patients diagnosed in summer had significantly more concomitant diseases. In patients with CD, the occurrence of the worst flare was more frequent in autumn. Furthermore, the season of birth was associated with Pediatric Crohn&rsquo, s Disease Activity Index at worst flare and earlier surgery. In conclusion, several clinical parameters are associated with insolation, the season of diagnosis and season of birth in the clinical course of Crohn&rsquo, s disease.

Background: Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenic cause of renal failure. For several decades, ADPKD was regarded as an adult-onset disease. In the past decade, it has become more widely appreciated that the disease course begins in childhood. However, evidence-based guidelines on how to manage and approach children diagnosed with or at risk of ADPKD are lacking. Also, scoring systems to stratify patients into risk categories have been established only for adults. Overall, there are insufficient data on the clinical course during childhood. We therefore initiated the global ADPedKD project to establish a large international pediatric ADPKD cohort for deep characterization., Methods: Global ADPedKD is an international multicenter observational study focusing on childhood-diagnosed ADPKD. This collaborative project is based on interoperable Web-based databases, comprising 7 regional and independent but uniformly organized chapters, namely Africa, Asia, Australia, Europe, North America, South America, and the United Kingdom. In the database, a detailed basic data questionnaire, including genetics, is used in combination with data entry from follow-up visits, to provide both retrospective and prospective longitudinal data on clinical, radiologic, and laboratory findings, as well as therapeutic interventions., Discussion: The global ADPedKD initiative aims to characterize in detail the most extensive international pediatric ADPKD cohort reported to date, providing evidence for the development of unified diagnostic, follow-up, and treatment recommendations regarding modifiable disease factors. 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Y.] Istanbul Univ, Fac Med, Pediat Nephrol Dept, Istanbul, Turkey.

Learning to avoid threats often occurs by observing others. Most previous research on observational fear learning (OFL) in humans has used pre-recorded standardized video of an actor and thus lacked ecological validity. Here, we aimed to enhance ecological validity of the OFL by engaging participants in a real-time observational procedure (35 pairs of healthy male friends, age 18–27). One of the participants watched the other undergo a differential fear conditioning task, in which a conditioned stimulus (CS+) was paired with an aversive electric shock and another stimulus (CS−) was always safe. Subsequently, the CS+ and CS− were presented to the observer to test the OFL. While the friend’s reactions to the shock elicited strong skin conductance responses (SCR) in all observers, subsequent differential SCRs (CS+ > CS−) were found only when declarative knowledge of the CS+/US contingency (rated by the participants) was acquired. Contingency-aware observers also showed elevated fear potentiated startle responses during both CS+ and CS− compared to baseline. We conclude that our real-time procedure can be effectively used to study OFL. The procedure allowed for dissecting two components of the OFL: an automatic emotional reaction to the response of the demonstrator and learning about stimulus contingency.

Background It has been suggested that apolipoprotein E (APOE) polymorphisms are associated with the risk of developing inflammatory bowel disease (IBD) and the early age of disease onset. However, there are no reports regarding the relationship with clinical characteristics and disease severity. Aim To summarise that APOE polymorphisms are associated with the risk of developing IBD and the early age of disease onset. Methods In total, 406 patients aged 3-18 with IBD (192 had ulcerative colitis and 214 had Crohn's disease) were genotyped using the TaqMan hydrolysis probe assay. Clinical expression was described at diagnosis and the worst flare by disease activity scales, albumin and C-reactive protein levels, localisation and behaviour (Paris classification). Systemic steroid intake with the total number of courses, immunosuppressive, biological, and surgical treatment with the time and age of the first intervention were determined. The total number of exacerbation-caused hospitalisations, the number of days spent in hospital due to exacerbation, the number of relapses, and severe relapses were also estimated. Results Ulcerative colitis patients with the APOEe4 allele had lower C-reactive protein values at diagnosis (P = 0.0435) and the worst flare (P = 0.0013) compared to patients with the APOEe2 allele and genotype APOEe3/e3. Crohn's disease patients with the APOEe2 allele scored lower on the Pediatric Crohn's Disease Activity Index at diagnosis (P = 0.0204). IBD patients with APOEe2 allele spent fewer days in the hospital due to relapse (P = 0.0440). Conclusion APOE polymorphisms are associated with the risk of developing IBD and the clinical expression of IBD. However, the clinical relevance of the differences identified is rather modest.

Purpose: The paper aimed to assess the gait pattern in children and adolescents with juvenile idiopathic arthritis (JIA) treated at the rehabilitation center and to assess changes in this pattern after the end of treatment and 9 months later. Methods: 50 children with JIA were enrolled into the study. 35 healthy volunteers were enrolled into the study for a comparison. Spatiotemporal and kinematic gait parameters were obtained using a movement analysis system. The Gait Deviation Index (GDI) was calculated. The assessment was performed three times: on the day of admission to the rehabilitation center, after the end of a 4-week treatment period and 9 months later. Results: With regard to the majority of spatiotemporal and kinematic parameters, differences in their distribution were highly statistically significant between the study group and the control group (p < 0.001). In two subsequent tests, differences were less significant when compared to the control group (p < 0.01). In the study group, ranges of motion in the sagittal plane in the hip (p < 0.01), knee (p < 0.001) and ankle joints (p < 0.01) increased significantly between tests 1 and 2, and 1 and 3. A significantly lower value of GDI was observed in the study group (right limb; p = 0.036). Conclusions: The gait pattern of children with JIA is significantly different from the one observed in healthy children. A rehabilitation program significantly improved gait in children with JIA, but differences compared to healthy children were still observed, and it indicates that the abnormal gait pattern became permanent in this group of subjects.

Background: Cerebral palsy (CP) children present complex and heterogeneous motor disorders that cause gait deviations. Clinical gait analysis (CGA) is used to identify, understand and support the management of gait deviations in CP. Children with CP often use ankle&ndash, foot orthosis (AFO) to facilitate and optimize their walking ability. The aim of this study was to assess whether the gait deviation index (GDI) and the gait variability index (GVI) results can reflect the changes of spatio-temporal and kinematic gait parameters in spastic hemiplegic CP children wearing AFO. Method: The study group consisted of 37 CP children with hemiparesis. All had undergone a comprehensive, instrumented gait analysis while walking, both barefoot and with their AFO, during the same CGA session. Kinematic and spatio-temporal data were collected and GVI and GDI gait indexes were calculated. Results: Significant differences were found between the barefoot condition and the AFO conditions for selected spatio-temporal and kinematic gait parameters. Changes in GVI and GDI were also statistically significant. Conclusions: The use of AFO in hemiplegic CP children caused a statistically significant improvement in spatio-temporal and kinematic gait parameters. It was found that these changes were also reflected by GVI and GDI. These findings might suggest that gait indices, such as GDI and GVI, as clinical outcome measures, may reflect the effects of specific therapeutic interventions in CP children.

INTRODUCTION Grip strength and blood pressure are strongly interrelated. Blood pressure is an essential component of arterial load, which modulates cardiac output. OBJECTIVES We aimed to asses the correlation between grip strength and both steady and pulsatile components of arterial load in patients with acute myocardial infarction. PATIENTS AND METHODS We included 295 participants (mean age, 63 years) with acute myocardial infarction. The following data were assessed: grip strength, echocardiography, local arterial stiffness, arterial tonometry, continuous arterial pulse, and beat‑to‑beat wave. RESULTS In univariable analyses, grip strength correlated with arterial stiffness (pulse wave velocity), ventricular-arterial coupling, and measures of pulsatile arterial load: aortic characteristic impedance (Zao), total arterial compliance (TAC), and central fractional arterial pulse pressure (cFPP). In a multivariable model including age, grip strength, body mass index, systolic blood pressure, sex, and descriptors of pulsatile load, the following remained associated with grip strength: Zao (R2 for the model = 0.58; P

INTRODUCTION Disseminated tumor cells (DTCs) are a subset of circulating tumor cells that migrate to the bone marrow. Colorectal cancer is a heterogeneous disease depending on the site of the primary tumor. OBJECTIVES We aimed to assess the association between the presence of DTCs in the bone marrow and tumor characteristics as well as long‑term treatment outcomes in patients with left‑sided colorectal cancer. PATIENTS AND METHODS This prospective study included 91 patients with left‑sided colorectal cancer (37 with colon cancer and 54 with rectal cancer) treated between 2007 and 2012 in a single tertiary center. Fifteen patients had stage I cancer; 26, stage II; 26, stage III; and 24, stage IV. Overall survival and cancer relapse rates were compared between patients with different cancer stages and DTC status. RESULTS Bone marrow DTCs were identified in 42 patients (46.1%). The prevalence of DTCs was not related to tumor infiltration depth, nodal involvement, distant metastasis, tumor stage, or primary tumor site. The 5‑year overall survival rates were 59.5% and 53% in the DTC‑positive and DTC‑negative groups, respectively (P = 0.19). There was a notable trend favoring survival in patients with DTCs with stage II and III disease (both separately and when combined). The number of metachronous distant metastases was significantly lower in DTC‑positive patients. CONCLUSIONS The presence of DTCs in the bone marrow is not associated with primary tumor characteristics and seems to reduce metastasis formation in left‑sided colorectal cancer. There is also a trend for improved overall survival in DTC‑positive patients. These results are intriguing and warrant further confirmation.

The neural plasticity underlying language learning is a process rather than a single event. However, the dynamics of training‐induced brain reorganization have rarely been examined, especially using a multimodal magnetic resonance imaging approach, which allows us to study the relationship between functional and structural changes. We focus on sign language acquisition in hearing adults who underwent an 8‐month long course and five neuroimaging sessions. We assessed what neural changes occurred as participants learned a new language in a different modality—as reflected by task‐based activity, connectivity changes, and co‐occurring structural alterations. Major changes in the activity pattern appeared after just 3 months of learning, as indicated by increases in activation within the modality‐independent perisylvian language network, together with increased activation in modality‐dependent parieto‐occipital, visuospatial and motion‐sensitive regions. Despite further learning, no alterations in activation were detected during the following months. However, enhanced coupling between left‐lateralized occipital and inferior frontal regions was observed as the proficiency increased. Furthermore, an increase in gray matter volume was detected in the left inferior frontal gyrus which peaked at the end of learning. Overall, these results showed complexity and temporal distinctiveness of various aspects of brain reorganization associated with learning of new language in different sensory modality., The current study focuses on sign language acquisition in hearing adults who underwent an 8‐month long training and five neuroimaging sessions. Using multimodal approach, we assessed what neural changes occurred over the course of learning—as reflected by task‐based activity, connectivity changes, and co‐occurring structural alterations. Overall, these results showed complexity and temporal distinctiveness of various aspects of brain reorganization associated with learning of new language in different sensory modality.