Pneumatic Balloon Dilation of Gastric Sleeve Stenosis Is Not Associated with Weight Regain.
Gastric sleeve stenosis (GSS) occurs in up to 4% of patients after laparoscopic sleeve gastrectomy (LSG). Typical symptoms include reflux, abdominal pain, dysphagia, and regurgitation. Serial pneumatic balloon dilation (PBD) is a successful treatment in many cases obviating the need for revisional surgery, but the potential for weight regain is unknown. The aim of the current study was to assess weight trends following serial pneumatic dilation for GSS. Retrospective analysis of a prospectively maintained database of patients undergoing serial PBD for GSS at one institution. Primary outcome was change in BMI before and after serial PBD. Secondary outcomes included complication rates and need for revisional surgery. Sub-group analyses were performed to determine the relationship of patient and procedural factors to BMI after PBD. Forty-four patients met inclusion criteria, 34 (84.1%) women. Mean age was 46.7 (SD 11.9). Mean pre-sleeve BMI was 47.8 (SD 9.2), and mean BMI prior to first dilation was 34.2 (SD 6.8). Median follow-up was 395 days (range 48-571). Mean BMI at time of last follow up was 33.7 (SD 6.7). There was no statistical difference in BMI pre- or post-PBD (p 0.980). The lowest 10th and highest 90th BMI percentile trended toward a higher and lower BMI after PBD, respectively, though not significant. As the prevalence of sleeve gastrectomy continues to rise, an increasing number of patients will require treatment for GSS. Stenosis is effectively treated with serial PBD in most patients without any impact on weight gain, making this an effective and appealing option for many patients.


[Endocrine tumors of the stomach and duodenum (including gastrinoma) - management guidelines (recommended by the Polish Network of Neuroendocrine Tumors)].
The neuroendocrine tumors of the stomach and duodenum constitute only minority of neoplasms in this localisation. However due to their clinical behaviour and/or hormonal syndromes they pose diagnostic and therapeutic challenge. They display distinct phenotypes, regarding their pathogenesis, pathology and clinical course. Herein we present Polish guidelines for biochemical, pathological and localisation diagnosis, and discuss therapeutic approaches, considering endoscopic and surgical treatment, pharmacological and radionuclide therapy.


Microglia as therapeutic target in central nervous system disorders.
Chronic microglial activation is associated with the pathogenesis of several CNS disorders. Microglia show phenotypic diversity and functional complexity in diseased CNS. Thus, understanding the pathology-specific heterogeneity of microglial behavior is crucial for the future development of microglia-modulating therapy for variety of CNS disorders. This review summarizes up-to-date knowledge on how microglia contribute to CNS homeostasis during development and throughout adulthood. We discuss the heterogeneity of microglial phenotypes in the context of CNS disorders with an emphasis on neurodegenerative diseases, demyelinating diseases, CNS trauma, and epilepsy. We conclude this review with a discussion about the disease-specific heterogeneity of microglial function and how it could be exploited for therapeutic intervention.


Managing necrotising fasciitis to reduce mortality and increase limb salvage.
Necrotising fasciitis is a rare soft-tissue infection with a high mortality rate. In this paper we describe our management protocol for necrotising fasciitis, focused on surgical approaches, which increased patients' survival rate. Between March 2009 and December 2014, patients suspected of having necrotising fasciitis (based on laboratory and MRI examinations), underwent management for the infection. A patient suspected of having necrotising fasciitis had surgical exploration performed within eight hours. Patients underwent serial debridement every 24-72 hours until infection had been fully eradicated, after which reconstructive surgery was considered. A total of 34 patients underwent management for necrotising fasciitis, 31 of which had the infection confirmed. From this group, the 18 patients who underwent free flap reconstructive surgery were included in the study, nine of which were female with a mean age of 54.3 (range: 28-77) years. The patients underwent 2-5 repeat debridements (mean: 3.5). Reconstructive procedures were latissimus dorsi (LD) myocutaneous flap in 11 patients, and latissimus dorsi chimeric flap in six patients; the remaining patient received an latissimus dorsi myocutaneous flap, an latissimus dorsi perforator flap and an anterolateral thigh flap simultaneously. Patients were discharged from hospital and returned to daily life three weeks after the final procedure. The mean length of follow-up was 34.8 months (range: 12-60 months). All 18 patients survived. With multidisciplinary management, the challenge of necrotising fasciitis can be overcome without risk of mortality risk.


Sesquiterpenoids Isolated from the Rhizomes of Genus Atractylodes.
Atractylodes plants have been used in traditional herbal medicine to treat gastrointestinal diseases and contain various chemical compounds. Sesquiterpenoids are the most important therapeutic compounds in Atractylodes rhizomes. Based on studies reported from 2000 to 2022, we classified sesquiterpenoids by their chemical skeletons and original resources. Moreover, we discussed their biosynthesis and physicochemical and pharmacological features. We reported sesquiterpenoids with skeletal moieties, such as monocyclic sesquiterpenes (bisabolene- and elemene-type), bicyclic sesquiterpenes (eudesmane-, isopterocarpolone-, hydroxycarissone-, eremophilane-, bisesquiterpenoid-, guaiane- and spirovetivane-type and eudesmane lactones) and tricyclic sesquiterpenes (cyperene- and patchoulene-type), with their biosynthetic pathways, chemical modifications and in vivo metabolites. The pharmacological activities of sesquiterpenoids as anti-inflammatory, anti-tumor, anti-diabetic and anti-microbial and for treating gastrointestinal disorders have been reported for this genus.


The effects of antithrombin III, heparin and a novel heparinoid infusions on the bleeding tendency using an experimental model in the rat.
The effects of selective increase of plasma AT-III concentration (to 2 U/ml and 8 U/ml) in the presence or absence of low dose commercial heparin and a novel natural heparinoid (Org 10172) on APTT, clotting factors and bleeding were investigated in an experimental model in rats. Slight increases in the APTT were observed with: a. Org 10172, b. both AT-III doses and c. combinations hereoff. However, synergism was observed in the prolongations of the APTT when the AT-III concentrate (70 U/kg and 500 U/kg) was combined with both heparin dosages. AT-III concentrates (70 U/kg and 500 U/kg) or Org 10172 (2,5 mg/kg) separately or in combination showed no effect on bleeding. Heparin (0, 125 and 0,25 mg/kg i.v.) also showed no effect on bleeding neither if they were combined with the lower dose AT-III. However, heparin (both dosages) combined with 500 U/kg of AT-III concentrates significant increased blood loss. These observations suggest that infusion of AT-III concentrate additionally to low dose heparin therapy did not increase bleeding in the rat model used provided that extreme high AT-III plasma levels (8 U/ml) were avoided. The novel natural heparinoid Org 10172 alone or combined with either AT-III dosage induced no increased bleeding.


Usefulness of the dizziness handicap inventory in the screening for benign paroxysmal positional vertigo.
The purpose of the study was to determine whether a newly developed subscale of the Dizziness Handicap Inventory (DHI) could assist in the screening of benign paroxysmal positional vertigo (BPPV). Retrospective case review. Tertiary balance referral center. Charts of 383 patients (mean age, 61 yr) with a variety of vestibular diagnoses (peripheral and central) were reviewed. Patients completed the DHI before the onset of physical therapy intervention. A newly developed BPPV subscale developed from current DHI items was computed to determine whether the score could assist the practitioner in identifying individuals with BPPV. Individuals with BPPV had significantly higher mean scores on the newly developed BPPV subscale of the DHI (p < 0.01). The five-item BPPV score was a significant predictor of the likelihood of having BPPV (chi2 = 8.35; p < 0.01). On the two-item BPPV scale, individuals who had a score of 8 of 8 were 4.3 times more likely to have BPPV compared with individuals who had a score of 0. Items on the DHI appear to be helpful in determining the likelihood of an individual having the diagnosis of BPPV.


Performance of tumor growth kinetics as an imaging biomarker for response assessment in colorectal liver metastases: correlation with FDG PET.
To correlate RECIST, volumetric criteria, and tumor growth kinetics at multidetector-computed tomography with tumor metabolic activity at FDG PET in colorectal liver metastases (CRCLM) treated with bevacizumab-based chemotherapy. Thirty-two CRCLM in 20 patients treated with bevacizumab-based chemotherapy were evaluated. Pre- and post-treatment CT scans were used to calculate reciprocal of doubling time (RDT), percentage change in the lesion's longest transaxial diameter (RECIST 1.1), and percentage change in the tumor volume. The accuracy of these parameters in predicting response based on standard uptake value analysis at FDG PET was assessed. Data were analyzed using Spearman's correlation, student's t, Mann-Whitney, Wilcoxon signed-rank, and Fisher's exact tests. According to FDG PET, 24/32 (75%) lesions were categorized as responders and 8/32 (25%) lesions as nonresponders. Based on RDT, 26/32 (81.25%) lesions were classified as responders and 6/32 (18.75%) lesions as nonresponders. Response classification according to RDT and FDG PET was concordant in 30/32 (93.75%) lesions, whereas RECIST 1.1 and volumetric criteria were concordant with FDG PET for 20/32 (62.5%) and 21/32 (65.63%) lesions, respectively. A strong association was found between RDT and response based on FDG PET (odds ratio = 127.4; 95% CI 5.54-2997; P < 0.0001). Tumor growth kinetics may be an effective imaging biomarker for response evaluation in CRCLM.


Knockdown of microRNA-96-5p resists oxidative stress-induced apoptosis in nucleus pulposus cells.
Intervertebral disc degeneration (IVDD) often leads to low back pain, which severely affects people's quality of life. Oxidative stress (OS) can accelerate nucleus pulposus cell (NPCs) senescence and apoptosis. Exploring the mechanism underlying OS-induced apoptosis is of utmost importance to aid in the development of IVDD treatment. In the current study, we tested the function of microRNA-96-5p in H2O2-treated NPCs. Apoptosis and mitophagy-related proteins were examined by western blot. Reactive oxygen species (ROS) generation, mitochondrial membrane potential, and apoptosis of NPCs were evaluated by flow cytometry. A luciferase reporter assay was conducted to confirm the interaction between microRNA-96-5p and Forkhead Box Protein O1 (FOXO1). H2O2 treatment enhanced apoptosis in NPCs and upregulated the microRNA-96-5p expression. It was shown that knockdown of microRNA-96-5p attenuated H2O2-induced OS and apoptosis. FOXO1 is a direct target of microRNA-96-5p, and knockdown of microRNA-96-5p enhanced PINK1/Parkin-mediated mitophagy by up-regulating FOXO1. Collectively, knockdown of microRNA-96-5p enhanced PINK1/Parkin-mediated mitophagy by up-regulating FOXO1. Our results facilitate the understanding of the role of microRNA-96-5p in IVDD and the mechanism of H2O2-induced oxidative damage.


Generic Direct Acting Antivirals in Treatment of Chronic Hepatitis C Infection in Patients of Thalassemia Major.
There is no published data of treating hepatitis C in thalassemia major patients with any sofosbuvir based direct acting antivirals (DAAs). This study was performed to determine the efficacy and safety of these regimes using generic drugs in the thalassemia major population. In this observational study, 902 patients of thalassemia major from five transfusion centres in Mumbai were screened for HCV antibody. Of the 120 positive patients, HCV RNA was detected in 50%. The first 29 patients were enrolled for evaluating the efficacy and safety of generic sofosbuvir based DAAs. The 29 patients' had a mean age of 24 years with genotype 1 in 17, genotype 3 in 11patients, while 1 patient's genotype could not be classified. Six patients had compensated cirrhosis and 8 patients were treatment experienced. SVR 12 was achieved in 100% of patients. There was significant increase in PRC (packed red cell) requirements (P = 0.0003) during treatment. At 12 weeks post-treatment, PRC requirements returned to baseline with a significant fall in serum ferritin (P = 0.03). Headache, fatigue and diarrhoea were the most common side effects. The difference in side effects including anaemia between patients who received ribavirin (19/29) and those who did not receive ribavirin (10/29) was not significant. Presence of diabetes, splenectomy, high ferritin or liver or heart iron overload on MRI T2* did not affect the efficacy of treatment. Generic DAAs are safe in thalassemia major patients with hepatitis C with efficacy of 100%. Serum ferritin falls significantly after treatment despite an increase in transfusion requirements during treatment.


Cardiorenal syndrome in the pediatric population: A systematic review.
The concept of cardiorenal syndrome (CRS) is derived from the crosstalk between the heart and kidneys in pathological conditions. Despite the rising importance of CRS, there is a paucity of information on the understanding of its pathophysiology and management, increasing both morbidity and mortality for patients. This review summarizes the existing conceptual pathophysiology of different types of CRS and delves into the associated therapeutic modalities with a focus on pediatric cases. Prospective or retrospective observational studies, comparative studies, case reports, case-control, and cross-sectional studies that include pediatric patients with CRS were included in this review. Literature was searched using PubMed, EMBASE, and Google Scholar with keywords including "cardio-renal syndrome, type," "reno-cardio syndrome," "children," "acute kidney injury," and "acute decompensated heart failure" from January 2000 to January 2021. A total of 14 pediatric studies were ultimately included and analyzed, comprising a combined population of 3608 children of which 32% had CRS. Of the 14 studies, 57% were based on type 1 CRS, 14% on types 2 and 3 CRS, and 7% were on types 4 and 5 CRS. The majority of included studies were prospective cohort, although a wide spectrum was observed in terms of patient age, comorbidities, etiologies, and treatment strategies. Commonly observed comorbidities in CRS type 1 were hematologic, oncologic, cardiology-related side effects, muscular dystrophy, and pneumonia/bronchiolitis. CRS, particularly type 1, is prevalent in children and has a significant risk of mortality. The current treatment regimen primarily involves diuretics, extracorporeal fluid removal, and treatment of underlying etiologies and comorbidities.


Optimal waist-to-height ratio values for cardiometabolic risk screening in an ethnically diverse sample of South African urban and rural school boys and girls.
The proposed waist-to-height ratio (WHtR) cut-off of 0.5 is less optimal for cardiometabolic risk screening in children in many settings. The purpose of this study was to determine the optimal WHtR for children from South Africa, and investigate variations by gender, ethnicity and residence in the achieved value. Metabolic syndrome (MetS) components were measured in 1272 randomly selected learners, aged 10-16 years, comprising of 446 black Africans, 696 mixed-ancestry and 130 Caucasians. The Youden's index and the closest-top-left (CTL) point approaches were used to derive WHtR cut-offs for diagnosing any two MetS components, excluding the waist circumference. The two approaches yielded similar cut-off in girls, 0.465 (sensitivity 50.0, specificity 69.5), but two different values in boys, 0.455 (42.9, 88.4) and 0.425 (60.3, 67.7) based on the Youden's index and the CTL point, respectively. Furthermore, WHtR cut-off values derived differed substantially amongst the regions and ethnic groups investigated, whereby the highest cut-off was observed in semi-rural and white children, respectively, Youden's index0.505 (31.6, 87.1) and CTL point 0.475 (44.4, 75.9). The WHtR cut-off of 0.5 is less accurate for screening cardiovascular risk in South African children. The optimal value in this setting is likely gender and ethnicity-specific and sensitive to urbanization.


Toward unraveling membrane biogenesis in mammalian autophagy.
Autophagy is a unique form of membrane trafficking, which delivers macromolecules and organelles from the cytoplasm to lysosomes for degradation. This fundamental and ubiquitous process in eukaryotic cells is mediated by the double-membrane-bound structures called autophagosomes, which transiently emerge in the cytoplasm. The recent remarkable explosion of knowledge of autophagy has revealed its multiple roles, especially in mammals; in addition to its basic role in turnover and reuse of cellular constituents, the process unexpectedly functions in elimination of invading bacteria and antigen presentation. Analysis of mammalian homologs of the autophagy-related (Atg) proteins identified in yeast has shed light on not only the common molecular mechanisms underlying autophagosome formation, but also specialized mechanisms that are related to the diverse functions and complex regulation of autophagy in higher organisms.


Individual Differences in Disqualifying Monitoring Underlie False Recognition of Associative and Conjunction Lures.
The current study leveraged experimental and individual differences methodology to examine whether false memories across different list-learning tasks arise from a common cause. Participants completed multiple false memory (associative and conjunction lure), working memory (operation and reading span), and source monitoring (verbal and picture) tasks. Memory discriminability in the associative and conjunction tasks loaded onto a single (general) factor and were unaffected by warnings provided at encoding. Consistent with previous research, source-monitoring ability fully mediated the relation between working memory and false memories. Moreover, individuals with higher source monitoring-ability were better able to recall contextual information from encoding to correctly reject lures. These results suggest that there are stable individual differences in false remembering across tasks. The commonality across tasks may be due, at least in part, to the ability to effectively use disqualifying monitoring processes.


Modeling of biotic and abiotic processes affecting phosphate oxygen isotope ratios in a mineral-water-biota system.
Abiotic and biotic reactions operate side by side in the cycling of phosphorus (P) in the environment, but the relative roles of these two reactions vary both spatially and temporally. In biotic reactions, the uptake and release of P are catalyzed by enzymes and thus change phosphate oxygen isotope ratios, while in abiotic reactions, the absence of hydrolysis-condensation reactions results in no apparent changes in isotope composition, except short-term kinetic isotope effect due solely to preferential ion exchange. Therefore, isotope method could be a promising tool to differentiate relative roles of these two reactions in the environment but the relationship of the dynamic concentration and isotope exchange at the biota-water interface is largely unknown. In this study, we aimed to develop a process-based isotope model underpinning the competition of abiotic (sorption, desorption, and ion exchange) and biotic (uptake, metabolism, and release) reactions during uptake and recycling of ferrihydrite-bound P by E. coli. Our model comprises equations describing the partitioning relationship among different P pools and their corresponding oxygen isotope compositions and is based exclusively on oxygen isotope exchange at multiple sites including mineral surface, aqueous phase, and bacterial cells. The process-based model adequately reproduced the measured concentration and isotope compositions over time. Furthermore, parametric and sensitivity analyses using the model indicated that the rate of biological uptake of P was the major factor controlling the changes of phosphate isotope composition. In conclusion, our model provides new insights into a mechanistic aspect of isotope exchange and could be potentially useful for future efforts to understand the interplay of biotic and abiotic factors on phosphorus cycling in natural environments.


A catalog of hemizygous variation in 127 22q11 deletion patients.
The 22q11.2 deletion syndrome is the most common microdeletion disorder, with wide phenotypic variability. To investigate variation within the non-deleted allele we performed targeted resequencing of the 22q11.2 region for 127 patients, identifying multiple deletion sizes, including two deletions with atypical breakpoints. We cataloged ~12,000 hemizygous variant positions, of which 84% were previously annotated. Within the coding regions 95 non-synonymous variants, three stop gains, and two frameshift insertions were identified, some of which we speculate could contribute to atypical phenotypes. We also catalog tolerability of 22q11 gene mutations based on related autosomal recessive disorders in man, embryonic lethality in mice, cross-species conservation and observations that some genes harbor more or less variants than expected. This extensive catalog of hemizygous variants will serve as a blueprint for future experiments to correlate 22q11DS variation with phenotype.


Evolutionary considerations on 5-HT2 receptors.
Serotonin is a neurotransmitter widely conserved from ancient organisms lacking nervous systems through man, and its presence precedes the appearance of nervous systems on both developmental and evolutionary time scales. Serotonin receptor subtypes diversified approximately at the time period during which vertebrates diverged from invertebrates. The biological and clinical importance of serotonin receptors, may benefit from studies on their evolution. Although potentially informative about their pathophysiological functions, reviews on this topic are sparse. Several observations support basic functions mediated by serotonin, both in periphery and central nervous system. In particular, 5-HT2B receptors have been implicated in embryonic development, including cell proliferation, survival, and/or differentiation, in either neural crest cell derivatives, myeloid cell lineage, or heart embryogenesis. In this review, we collected existing data about the genomic association between the RPN2 proteasome subunit gene Psmd1 and the 5-HT2B receptor gene Htr2b. We discuss about the possibility that, during genome duplications, a single copy of this pair of genes has been conserved, suggesting a strong selective pressure. Many basic physiological functions in which serotonin system is involved could be linked to the early association of these two genes in pre-vertebrates. Their evolutionary association highlights the possibility that the 5-HT2B receptor gene, Htr2b, is the common ancestor of 5-HT2A/2B/2C-receptor subfamily. Disentangling these possibilities could bring new understanding of the respective importance of these receptors in pathophysiology of serotonin.


Assessment of lutein and zeaxanthin status and dietary markers as predictors of the contrast threshold in 2 age groups of men and women.
Lutein and zeaxanthin (L + Z) status is associated with the macular pigment (MP). The relationship between MP and visual function is controversial. We hypothesized that, within the framework of nutrition, visual function was related to MP and nutritional and/or/dietary factors influencing it. A cross-sectional study was performed in 108 volunteers divided into 2 age groups (20-35 years; 45-65 years), each 27 women and 27 men, to assess the relationship between MP optical density (MPOD) and contrast threshold (CT), considering the influence of L + Z and, fruit and vegetable (F + V) intake. MPOD, L + Z in serum and dietary intake were determined using heterochromatic flicker photometry, high-performance liquid chromatography and 3-day food records, respectively. CT was measured with the CGT-1000 Contrast Glaretester at 6 stimulus sizes, with and without glare. Spearman correlation coefficient and a generalized linear model were used for the statistical study. MPOD and CT were higher and lower, respectively in younger than in elder individuals (P < .000) and were correlated only in the older group. CT were higher under glare conditions, at the intermediate and smaller visual angles, with greater differences in the older (P < .003) than the younger group (P < .014). In the total sample, CT correlated inversely with MPOD (correlation coefficients and P values ranging from -.245 to -.152 and from .000 to .026, respectively) and directly with F + V intake (correlation coefficients and P values ranging from -.265 to -.176 and from .000 to .010, respectively). As predictors of CT in the total sample, MPOD, F + V (every 100 g/d) and sex were identified (β coefficients ranged from -0.01 to -1.86; from 0.01 to 0.08 and from 0.01 to 0.40, respectively). CT revealed age-specific nutritional predictors: MPOD and serum lutein in the 45- to 65-year group, and F + V intake in the 20- to 35-year group.


Protein stability effects of a complete set of alanine substitutions in Arc repressor.
The equilibrium stabilities of a complete set of single alanine-substitution mutants of the Arc repressor of bacteriophage P22 have been determined by thermal and urea denaturation experiments. Only half the alanine substitutions cause significant changes in stability, with the most deleterious mutations affecting side chains in the hydrophobic core or in salt bridges and hydrogen bonds which are protected from solvent. The five mutations that are most destabilizing affect a cluster of core residues that seem to form a structural foundation for Arc.


[Possibilities and limits of application of fluoride-containing varnish in caries prevention, for example, "Fluor-Protector" (2)].
Using selected literature, the author provides an overview of the possibilities and limits of fluoride varnish application in caries prophylaxis based on the example of Fluor-Protector. He concludes, as did de Bruyn and Arends (1987), that Fluor-Protector is a safe and effective agent that can prevent caries very effectively and is also promising for use as a desensitising substance.


Circulating t-PA antigen predicts major adverse coronary events in patients with stable coronary artery disease--a 13-year follow-up.
Thrombus formation after rupture of an atherosclerotic plaque plays a crucial role in coronary artery disease (CAD). A decreased endogenous fibrinolytic system and prothrombotic factors are supposed to influence coronary thrombosis. It was our aim to investigate the predictive value of tissue plasminogen activator (t-PA) antigen, von Willebrand Factor, Lipoprotein (a) and anti-cardiolipin antibodies for major adverse coronary events in patients with stable CAD in a prospective cohort study of more than 10 years. We observed 141 patients with angiographically proven CAD for a median follow-up period of 13 years. t-PA antigen was the only marker predicting coronary events (logistic regression, p = 0.044) with a poor prognosis for patients in the 5th quintile with an odds ratio of 7.3 (compared to the 1st quintile). The odds ratio even increased to 10.0 for coronary events associated with the "natural course" of CAD excluding events due to restenosis. t-PA antigen had a slightly higher prognostic power (ROC curve; AUC = 0.69) than fasting glucose (AUC = 0.68) and cholesterol (AUC = 0.67). Triglycerides influenced plasma levels of t-PA antigen (regression, p < 0.001). The predictive value of t-PA antigen remained significant after adjustment for inflammation (logistic regression, p = 0.013) and extent of CAD (p = 0.045) but disappeared adjusting for insulin resistance (p = 0.12). In conclusion t-PA antigen predicted coronary events during a very long-term follow-up with a comparable prognostic power to established cardiovascular risk factors. Markers of insulin resistance influenced t-PA antigen and its predictive value.