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This article provides a comprehensive analysis of calcaneal apophysitis, or Sever's disease, a major cause of heel pain in children. This overuse injury stems from repetitive mechanical stress on the calcaneal apophysis, often intensified by rapid growth spurts and high physical activity. It is particularly prevalent among young athletes involved in sports with repetitive impact. The condition's pathophysiology involves microtrauma and inflammation at the calcaneus's secondary ossification center due to traction forces from the Achilles tendon. Diagnosis is primarily clinical while imaging is used to rule out other conditions. Symptoms include localized heel pain and tenderness, worsened by activity. Risk factors encompass intrinsic elements like limited ankle dorsiflexion and foot alignment issues, and extrinsic factors such as intense physical activity. Management mainly involves conservative treatments: rest, NSAIDs, stretching exercises, and orthotics. Physical therapy and proper footwear are also effective. Prevention focuses on maintaining a healthy weight, adequate rest, supportive footwear, low-impact activities, and regular stretching to reduce re-injury risk.

Many organisms, including beneficial entomopathogenic nematodes (EPNs), are commonly found in the soil environment. EPNs are used as biopesticides for pest control. They have many positive characteristics and are able to survive at sites of application for a long time, producing new generations of individuals. The occurrence of populations depends on many environmental parameters, such as temperature, moisture, soil texture, and pH. Extreme temperatures result in a decrease in the survival rate and infectivity of EPNs. Both high humidity and acidic soil pH reduce populations and disrupt the biological activity of EPNs. Nematodes are also exposed to anthropogenic agents, such as heavy metals, oil, gasoline, and even essential oils. These limit their ability to move in the soil, thereby reducing their chances of successfully finding a host. Commonly used fertilizers and chemical pesticides are also a challenge. They reduce the pathogenicity of EPNs and negatively affect their reproduction, which reduces the population size. Biotic factors also influence nematode biology. Fungi and competition limit the reproduction and survival of EPNs in the soil. Host availability enables survival and affects infectivity. Knowledge of the influence of environmental factors on the biology of EPNs will allow more effective use of the insecticidal capacity of these organisms.

Autism spectrum disorders (ASD) is a neurodevelopmental disorder influenced by a number of genetic and environmental factors. It is characterized by a broad range of symptoms, particularly in the areas of communication and language, which pose a therapeutic challenge for both parents and therapists. This article, based on a review of available studies on PubMed, presents therapeutic methods based on functional communication strategies and ways to implement them as a form of treatment for children with the autism spectrum disorders. The major goals of ASD treatment are socialization and communication skills improvement and current treatments are not based on pharmacological therapies, but on behavioral therapies. Through appropriate speech development and practical communication strategies that are based on techniques like motivating the child to create eye contact with an adult, it is possible to realize the development of proper communication. These strategies are a form of therapy and allow for the improvement of the child's communication on multiple levels and shaping the social attitudes. Incorporating suitable therapeutic communication techniques enables the development and enhancement of social skills in children with autism spectrum disorders. Children with ASD benefit from appropriate communication because it helps them communicate their needs, understand the social norms, and improve their quality of life.

Introduction: Alzheimer's disease is a degenerative disease of the brain, caused by the deposition of beta-amyloid and tau protein. It is characterized by progressive memory and behavior disorders which, over time, completely prevent the patient from functioning properly in everyday life, performing work and disrupting social contacts. Communication problems arise and patients forget more and more words. Unfortunately, we are not able to completely stop the progression of this disease, but we can only delay its development. To delay the progression of the disease, pharmacotherapy includes acetylcholinesterase inhibitors and NMDA receptor antagonists. Matherials and methods: This article, based on a PubMed review of available research, examines the impact of rivastigmine, donepezil, memantine and psychotherapy on delaying disease progression. Results: A number of studies have investigated the effect of 6-12 milligrams of rivastigmine, 10 milligrams of donepezil and 20 milligrams of memantine on patients' ability to communicate. The results were checked using the MMSE, ADAS or SIB scales and interviews conducted regularly by clinicians. In addition, patients were subjected to various forms of psychotherapy, including reminiscence therapy and cognitive therapy. All groups experienced significantly less deterioration in their functional stage of disease compared to the placebo groups. Conclusions: The best results in the treatment of Alzheimer's disease can be obtained by combining pharmacological therapy with non-pharmacological effects. Thanks to this form of treatment, the progression of the disease is delayed, and patients retain their communication abilities for longer.

Major Depressive Disorder(MDD) is serious psychiatric condition and they affect one in five people during their lifetime, the annual prevalence rates for the US population are 7.1% among adults, slightly more common among women (8.7%) than men (5.3%). Selective serotonin reuptake inhibitors are among the pharmacological agents most commonly used in the treatment of MDD. The mechanism of action of antidepressants is not yet fully understood. Currently, it is believed that the mechanism of the so-called down-regulation, i.e. reducing the density of receptors in the postsynaptic membrane, in this case mainly 5HT2 receptors. All of the antidepressants in use today have some common side effects. The side effect that will be discussed in the broadest possible way in this paper are sexual dysfunctions appearing during the therapy. Measuring the degree to which a given substance affects the sexual function of a patient diagnosed with MDD encounters many difficulties on its way. There are currently several questionnaires enabling such an assessment, the most common are CSFQ, ASEX and SexFX. Also the major problem is Post SSRI Sexual Disfunction. A number of animal studies have proven that prolonged exposure to SSRIs leave permanent changes in the CNS, but unfortunately, similar studies have not yet been conducted in humans. The aim of this study is to present the problem of sexual dysfunction as a side effect of SSRI therapy, to present the causes and to propose a strategy to combat SSRI-induced sexual dysfunctions.

Rhizobium leguminosarum bv. trifolii produces exopolysaccharide (EPS) composed of glucose, glucuronic acid, and galactose residues at a molar ratio 5:2:1. A majority of genes involved in the synthesis, modification, and export of exopolysaccharide are located in the chromosomal Pss-I region. In the present study, a ΔpssJ deletion mutant was constructed and shown to produce EPS lacking terminal galactose in the side chain of the octasaccharide subunit. The lack of galactose did not block EPS subunit translocation and polymerization. The in trans delivery of the pssJ gene restored the production of galactose-containing exopolysaccharide. The mutant was compromised in several physiological traits, e.g., motility and biofilm production. An impact of the pssJ mutation and changed EPS structure on the symbiotic performance was observed as improper signaling at the stage of molecular recognition, leading to formation of a significant number of non-infected empty nodules. Terminal galactosyltransferase PssJ was shown to display a structure typical for the GT-A class of glycosyltransferases and interact with other GTs and Wzx/Wzy system proteins. The latter, together with PssJ presence in soluble and membrane protein fractions indicated that the protein plays its role at the inner membrane interface and as a component of a larger complex.

The paper presents results of the research performed in order to determine causes of corrosion of the part made of austenitic steel of the X2CrNi18-9 grade. In particular the corrosion was observed in the areas of welded joints. It has been found that the cause of the corrosion was presence of the sigma phase precipitated during welding of the tested structural components. Also, it has been found that austenite shows the anodic character in relation to the sigma phase, which led to initiation of corrosion pits, as a result of the galvanic effect created, and further development of the corrosion. in polish Korozja połączenia spawanego wykonanego na stali austenitycznej X2CrNi18-9 wywołana występowaniem fazy sigma W pracy przedstawiono wyniki badań przeprowadzonych w celu ustalenia przyczyny wystąpienia korozji elementu wykonanego ze stali austenitycznej gatunku X2CrNi18-9. Korozję obserwowano w szczególności w obszarach występowania złączy spawanych. Stwierdzono, że przyczyną powstania korozji była obecność fazy sigma wydzielonej podczas spawania badanych elementów konstrukcyjnych. Stwierdzono, że austenit wykazuje anodowy charakter w stosunku do fazy sigma, co prowadzi do inicjacji wżerów korozyjnych w wyniku powstającego efektu galwanicznego i dalszego rozwoju korozji.

The paper presents results of the research performed in order to examine the e ciency of using of penetrant testing method to detect welding defects in welding joints made of Inconel 713C alloy. As a reference method, the microscopic observations have been used. It has been found that the penetrant testing method does not reveal all the cracks which can be detected using microscopic observations. in polish Metody badań złączy spawanych na superstopie Inconel 713C – nieniszczące badania penetracyjne oraz obserwacje mikroskopowe W pracy przedstawiono wyniki badań przeprowadzonych w celu oceny przydatności nieniszczących badań penetracyjnych w zastosowaniu do badania złączy spawanych wykonanych na superstopie niklu Inconel 713C. Jako metodę odniesienia wykorzystano obserwacje mikroskopowe. Stwierdzono, że metoda penetracyjna nie ujawniła wszystkich pęknięć wykrytych podczas obserwacji mikroskopowych.

Omnipresent suppressive myeloid populations in the tumor microenvironment limit the efficacy of T-cell-directed immunotherapies, become more inhibitory after administration of T-cell checkpoint inhibitors, and are overall associated with worse survival of cancer patients. In early clinical trials, positive outcomes have been demonstrated for therapies aimed at repolarizing suppressive myeloid populations in the tumor microenvironment. We have previously described the key role of P-selectin glycoprotein ligand-1 (PSGL-1) in maintaining an inhibitory state of tumor-associated macrophages (TAMs), most of which express high levels of PSGL-1. Here we describe a novel, first-in-class humanized high-affinity monoclonal antibody VTX-0811 that repolarizes human macrophages from an M2-suppressive phenotype towards an M1 inflammatory phenotype, similar to siRNA-mediated knockdown of PSGL-1. VTX-0811 binds to PSGL-1 of human and cynomolgus macaque origins without inhibiting PSGL-1 interaction with P- and L-Selectins or VISTA. In multi-cellular assays and in patient-derived human tumor cultures, VTX-0811 leads to the induction of pro-inflammatory mediators. RNAseq data from VTX-0811 treated ex vivo tumor cultures and M2c macrophages show similar pathways being modulated, indicating that the mechanism of action translates from isolated macrophages to tumors. A chimeric version of VTX-0811, consisting of the parental murine antibody in a human IgG4 backbone, inhibits tumor growth in a humanized mouse model of cancer. VTX-0811 is exceptionally well tolerated in NHP toxicology assessment and is heading into clinical evaluation after successful IND clearance.

Abstract Background To examine morphological and functional results after pars plana vitrectomy (PPV) with sulfur hexafluoride (SF6) gas tamponade due to macula-on and macula-off rhegmatogenous retinal detachment (RRD) during 6 months of the follow-up. Methods The study included 62 eyes that underwent successful PPV with SF6 tamponade with macula-on (34 eyes) and macula-off (28 eyes) RRD preoperatively. The best-corrected visual acuity (BCVA), Amsler test, M-charts, optical coherence tomography (OCT) and microperimetry were performed at 1, 3 and 6 months postoperatively. Results Results of the Amsler test were abnormal postoperatively in 54% of the patients in the group with macula-off and in 32% of the patients with macula-on RRD. Horizontal M-charts improved significantly from 0.33 to 0.2, vertical M-charts– from 0.29 to 0.17 during 6 months of the follow-up. There was a significant increase in the central retinal thickness (CRT) and average thickness (AT) between follow-up examinations only in the macula-off group. 29 of 62 eyes (47%) after surgery (equally with macula-on and macula-off RRD) showed morphological changes in OCT in the macular region, as epiretinal membrane, macular edema, subretinal fluid or alterations of the outer layers of the retina. The average threshold in microperimetry increased significantly within both groups during the follow-up. Conclusion Both horizontal and vertical M-charts scores, as were as microperimetry sensitivity improved significantly during the 6 months of the follow-up both in macula-on and macula-off group. Although PPV with SF6 gas tamponade was successful, almost half of eyes revealed anatomical changes in the macular region in OCT both with macula-on and macula-off group. Trial Registration Current Controlled Trials NCT03902795 registered on 03/04/2019. Retrospectively registered.

PurposeTo assess the pain intensity of two intracameral anesthetic solutions in patients undergoing cataract surgery and evaluate the factors influencing the patients’ postoperative activities.MethodsSixty-two patients undergoing cataract surgery were randomized to receive the study drug – a manufactured solution of 0.02% tropicamide/0.31% phenylephrine/1% lidocaine (Mydrane) or a traditional anesthetic formulation - solution of 1% lidocaine/0.025% adrenaline as an intraocular anesthetic. The pain intensity was assessed by Visual Analog Scale for Pain (VAS Pain) and Brief Pain Inventory-short form (BPI) on the next day after the surgery.ResultsThe mean pain score measured preoperatively with VAS Pain was 0.34 in Mydrane group and 0.09 in the reference group (p = 0.51). There were no statistically significant differences between the two anesthetic methods with respect to pain intensity during the surgery (p = 0.94) and the influence of pain during the last 24 h on activity (p = 0.79), mood (p = 0.31), social contacts (p = 0.29), sleep (p = 0.5) and the joy of life (p = 0.39). Additionally, there was no statistically significant influence of age, sex, lateralization, co-existing ophthalmological diseases (p = 0.98) and post-operative complications (p = 0.4) on the experienced pain measured during the surgery and in the last 24 h.ConclusionsNew commercially available intraocular anesthetic solution (Mydrane™) seems to be as effective as off-label traditional anesthetic formulation, in reducing the pain experienced during cataract surgery under topical anesthesia.

Purpose. To study the features in OCT-angiography and microperimetry in eyes with persistent full-thickness macular hole (FTMH) closed with the secondary plana vitrectomy (PPV) with autologous internal limiting membrane (ILM) plug. Methods. Secondary PPV was performed with closing the persistent FTMH with ILM plug, C3F8 tamponade, and face-down positioning. Four patients were followed for 6 months with best corrected visual acuity (BCVA) measurement, SD-OCT and OCT-A, and microperimetry. The results were compared with the fellow eye; in two patients, it was the healthy eye, and in two remaining eyes, successfully closed FTMH after primary PPV. Results. ILM flap was integrated in all cases with V-shape of closure, and atrophy was found in one case, with the largest diameter of FTMH. BCVA improved in two cases and remained the same in two cases. In OCT-A, the area of foveal avascular zone (FAZ) was larger, and foveal vessel density (FVDS) was smaller in eyes after secondary PPV in comparison to fellow eyes. In microperimetry, retinal sensitivity was lower in eyes after secondary PPV, and eccentric fixation was found in 2 of 4 patients. Conclusion. Although the anatomical results of repeated surgeries of FTMH with ILM plug are favorable, visual function results may be limited. Secondary closure of FTMH with ILM plug may lead to atrophy, changes in the macular vasculature, and eccentric fixation. The trial is registered with NCT03701542.

A 51 year-old female was presented with worsening of vision in her right eye; left eye similar problem about one year earlier. Each time responded to methylprednisolone sodium succinate and her discharge diagnosis was the optic nerve neuropathy. The past medical history (PMHx) was remarkable for twenty years of hypertension, anemia of chronic disease and currently on hemodialysis due to her end stage renal disease (ESRD). The most notable part of PMHx was the sacral area pain since her pregnancy at age 28 which had never resolved until the radiational therapy for aneurysmal bone cyst (ABC) which was found in CT imaging. Since the lower back pain is a frequent complain in pregnancy and after deliveries, the complains were neglected until the tumor became unresectable. The radiation therapy produced the shrinkage of ABC, but caused renal injury leading to HTN and ESRD. At age approximately 48, the patient started experiencing worsening of her vision in her left eye, most likely in result of poorly controlled HTN while maintaining her normal vision in her right eye. As stated in the report, the patient was treated in our clinic for worsening of vision in her left eye followed by he vision worsening in her right eye within one year. During the most recent hospitalization a diagnosis of bilateral papilledema we established and left eye’s optic nerve head atrophy was confirmed using both OCT and MR imaging. We believe that ignoring common complaints can lead to uncommon complications causing the most severe consequences for our patients.

Central retinal artery occlusion (CRAO) is an ophthalmic emergency, most commonly caused by an embolism, usually from the carotid arteries. It can be considered as an acute stroke of the eye, and is an ocular analogue of cerebral stroke. The incidence of CRAO is estimated to be 1 in 100 000 people. Risk factors include hypertension, carotid atherosclerosis, structural cardiac pathology, coronary heart disease, cerebral vascular accident, and diabetes mellitus. CRAO usually presents with a sudden, painless loss of vision. 52 - year old male was admitted to the Ophthalmology ER, reporting a painless monocular vision loss in a right eye for two days. After such a long time from the occurrence of symptoms, there weren’t any possible treatment methods for this patient, besides preventing future embolic events. Ophthalmological examination showed only a light perception in a right eye and vision in the left eye was 1.0. Patient was diagnosed to identify risk factors of CRAO: hypertension, hypercholesterolemia, atherosclerosis or thrombophilia. He was qualified for a careful observation for the atherosclerotic risk factors and educated, that in case of occurrence of the similar symptoms, he needs to report to a Ophthalmologist immediately. Currently, there are two main types of treating an acute non-arteritic CRAO: the first: ‘standard’, non-invasive method, and the second: using the thrombolytics deployed intravenously or intra-arterially. Unfortunately, they couldn’t be used to treat described patient, since he has already been in a late phase of CRAO.

Kynurenines, products of tryptophan (TRP) metabolism, display neurotoxic (e.g., 3-hydroxykynurenine; 3-HK), or neuroprotective (e.g., kynurenic acid; KYNA) properties. Imbalance between the enzymes constituting the kynurenine pathway (KP) plays a role in several disease, including neurodegeneration. In this study, we track changes in concentrations of tryptophan and its selected metabolites after damage to retinal ganglion cells and link this data with expression of KP enzymes. Brown-Norway rats were subjected to intravitreal N-methyl-D-aspartate (NMDA) injection or partial optic nerve crush (PONC). Retinas were collected 2 and 7 days after the completion of PONC or NMDA injection. Concentrations of TRP, kynurenine (KYN), and KYNA were determined by high performance liquid chromatography (HPLC). Data on gene expression in the rat retina were extracted from GEO, public microarray experiments database. Two days after NMDA injection concentration of TRP decreased, while KYN and KYNA increased. At day 7 compared to day 2 decrease of KYN, KYNA and further reduction of TRP concentration were observed, but on day 7 KYN concentration was still elevated when compared to controls. At day 2 and 7 after NMDA injection no statistically significant alterations of 3-HK were observed. TRP and 3-HK concentration was higher in PONC group than in controls. However, both KYN and KYNA were lower. At day seven concentration of TRP, 3-HK, and KYN was higher, whereas concentration of KYNA declined. In vivo experiments showed that retinal damage or optic nerve lesion affect TRP metabolism via KP. However, the pattern of changes in metabolite concentrations was different depending on the model. In particular, in PONC KYNA and KYN levels were decreased and 3-HK elevated. These observations correspond with data on expression of genes encoding KP enzymes assessed after optic nerve crush or transection. After intraorbital optic nerve crush downregulation of KyatI and KyatIII between 24 h and 3 days after procedure was observed. Kmo expression was transiently upregulated (12 h after the procedures). After intraorbital optic nerve transsection (IONT) Kmo expression was upregulated after 48 h and 7 days, KyatI and KyatIII were downregulated after 12, 48 h, 7 days and upregulated after 15 days. Collected data point to the conclusion that development of therapeutic strategies targeting the KP could be beneficial in diseases involving retinal neurodegeneration.

Purpose. To examine the relationship between the morphological and functional results in eyes after pars plana vitrectomy (PPV) with internal limiting membrane (ILM) peeling due to stage 4 full-thickness macular hole (FTMH). Methods. The study included 22 eyes that underwent successful PPV due to FTMH. Both vertical metamorphopsia (VM) and horizontal metamorphopsia (HM) were determined using type 2 M-charts, as well as best-corrected visual acuity (BCVA), microperimetry, and optical coherence tomography (OCT) were performed before PPV and 1 and 6 months postoperatively. Results. A significant improvement of BCVA and metamorphopsia scores measured by M-charts in particular periods before surgery, 1 and 6 months after PPV, was observed. The VM scores were consistently higher than the HM scores at all assessment times. There was a correlation found between VM and BCVA and microperimetry parameters before surgery. The macular sensitivity (MS) as well as macular integrity index increased from 1 month to 6 months after PPV and were correlated with postoperative visual acuity (VA). There was a correlation found between the hole diameter and MS and P2 parameter 6 months after PPV. There was a correlation found between mean duration of symptoms of FTMH and VA and VM score. Conclusions. VM scores seem to correlate better than HM scores with preoperative BCVA, microperimetry parameters, and duration of symptoms of the FTMH. VM scores are higher after PPV than HM scores in patients with stage 4 of the FTMH. This trial is registered with NCT03701542.

Background: It has been shown that a possible pathogenetic mechanism of neurodegeneration in the mouse model of glaucoma (DBA/2J) may be an alteration of kynurenic acid (KYNA) in the retina. This study aimed to verify the hypothesis that alterations of tryptophan (TRP) metabolism in DBA/2J mice is not limited to the retina. Methods: Samples of the retinal tissue and serum were collected from DBA/2J mice (6 and 10 months old) and control C57Bl/6 mice of the same age. The concentration of TRP, KYNA, kynurenine (KYN), and 3-hydroxykynurenine (3OH-K) was measured by HPLC. The activity of indoleamine 2,3-dioxygenase (IDO) was also determined as a KYN/TRP ratio. Results: TRP, KYNA, L-KYN, and 3OH-K concentration were significantly lower in the retinas of DBA/2J mice than in C57Bl/6 mice. 3OH-K concentration was higher in older mice in both strains. Serum TRP, L-KYN, and KYNA concentrations were lower in DBA/2J than in age-matched controls. However, serum IDO activity did not differ significantly between compared groups and strains. Conclusions: Alterations of the TRP pathway seem not to be limited to the retina in the murine model of hereditary glaucoma.

There is increased interest in following a healthy lifestyle and consuming a substantial portion of secondary plant metabolites, such as polyphenols, due to their benefits for the human body. Food products enriched with various forms of fruits and vegetables are sources of pro-health components. Nevertheless, in many cases, the level of their activities is changed in in vivo conditions. The changes are strictly connected with processes in the digestive system that transfigure the structure of the active compounds and simultaneously keep or modify their biological activities. Much attention has focused on their bioavailability, a prerequisite for further physiological functions. As human studies are time consuming, costly and restricted by ethical concerns, in vitro models for investigating the effects of digestion on these compounds have been developed to predict their release from the food matrix, as well as their bioaccessibility. Most typically, models simulate digestion in the oral cavity, the stomach, the small intestine and, occasionally, the large intestine. The presented review aims to discuss the impact of in vitro digestion on the composition, bioaccessibility and antioxidant activity of food polyphenols. Additionally, we consider the influence of pH on antioxidant changes in the aforementioned substances.

Aim. To report outcomes of pars plana vitrectomy (PPV) in pediatric retinal detachment (RD) with proliferative vitreoretinopathy (PVR), complications, factors influencing the final anatomical and functional results. Methods. Retrospective consecutive case series of 14 eyes. Average postoperative follow-up period was 34 months. Results. Mean age of patients was 10 years; eleven patients (79%) were males. The most common etiology was trauma (57%), the second—myopia (36%) and one case of uveitis (7%). At the day of presentation, the best-corrected visual acuity (BCVA) was worse than hand motion (50%); macula was detached in 86% of cases. Simultaneous PPV and phacoemulsification with intraocular lens (IOL) implantation were performed in 12 cases (86%). The most common endotamponade during PPV was silicone oil (93%). Anatomic reattachment was accomplished in 86% of cases. Final BCVA was equal or better than 0.1 in 50% of patients. The postoperative complications were found in 5 eyes (36%). Conclusion. Complete PPV was allowed for anatomically reattached retina and preserved vision in pediatric complex RD with PVR. However, visual outcomes were not satisfactory. Preserving vision in children with RD is of great importance for their future motor and intellectual development. This trial is registered with ClinicalTrials.gov Identifier: NCT03208205.