FRL and DAAM are required for lateral adhesion of interommatidial cells and patterning of the retinal floor.

Optical insulation of the unit eyes (ommatidia) is an important prerequisite of precise sight with compound eyes. Separation of the ommatidia is ensured by pigment cells that organize into a hexagonal lattice in the Drosophila eye, forming thin walls between the facets. Cell adhesion, mediated by apically and latero-basally located junctional complexes, is crucial for stable attachment of these cells to each other and the basal lamina. Whereas former studies have focused on the formation and remodelling of the cellular connections at the apical region, here, we report a specific alteration of the lateral adhesion of the lattice cells, leaving the apical junctions largely unaffected. We found that DAAM and FRL, two formin-type cytoskeleton regulatory proteins, play redundant roles in lateral adhesion of the interommatidial cells and patterning of the retinal floor. We show that formin-dependent cortical actin assembly is crucial for latero-basal sealing of the ommatidial lattice. We expect that the investigation of these previously unreported eye phenotypes will pave the way toward a better understanding of the three-dimensional aspects of compound eye development.

The NKCC1 ion transporter modulates microglial phenotype and inflammatory response to brain injury in a cell-autonomous manner.

The NKCC1 ion transporter contributes to the pathophysiology of common neurological disorders, but its function in microglia, the main inflammatory cells of the brain, has remained unclear to date. Therefore, we generated a novel transgenic mouse line in which microglial NKCC1 was deleted. We show that microglial NKCC1 shapes both baseline and reactive microglia morphology, process recruitment to the site of injury, and adaptation to changes in cellular volume in a cell-autonomous manner via regulating membrane conductance. In addition, microglial NKCC1 deficiency results in NLRP3 inflammasome priming and increased production of interleukin-1ß (IL-1ß), rendering microglia prone to exaggerated inflammatory responses. In line with this, central (intracortical) administration of the NKCC1 blocker, bumetanide, potentiated intracortical lipopolysaccharide (LPS)-induced cytokine levels. In contrast, systemic bumetanide application decreased inflammation in the brain. Microglial NKCC1 KO animals exposed to experimental stroke showed significantly increased brain injury, inflammation, cerebral edema and worse neurological outcome. Thus, NKCC1 emerges as an important player in controlling microglial ion homeostasis and inflammatory responses through which microglia modulate brain injury. The contribution of microglia to central NKCC1 actions is likely to be relevant for common neurological disorders.

Formation of Three-Dimensional Polysuccinimide Electrospun Fiber Meshes Induced by the Combination of CaCl2 and Humidity.

Even though electrospinning is getting more and more attention, the preparation of 3D nanofibrous meshes is still a big challenge that limits the application of electrospun materials, especially in tissue engineering. To overcome this problem, several solutions are introduced but most of them focus on the postprocessing of the electrospun meshes. This paper presents a straightforward novel method that utilizes the joint effect of the addition of CaCl2 and the relative environmental humidity (RH), which can induce the random 3D formation of polysuccinimide (PSI) electrospun fibers with different such as wrinkled or ribbon-like structures. Although the effect of humidity and inorganic salt additives on the micro and macrostructure of electrospun fibers is known, the connection between the two in this manner has never been presented. To investigate the effect, fibers with different PSI and CaCl2 concentrations at different humidity RH levels are prepared, and their microstructure is visualized with high-resolution scanning electron microscopy (SEM). To reveal the nature of the interaction between the polymer and the CaCl2, Fourier-transformed infrared (FTIR), X-ray diffraction (XRD), and thermogravimetry (TGA) measurements are carried out and 3D nanofibrous structures are obtained.

Statistical evaluation of measured biomechanical properties of human brain aneurysm samples.

Background and purpose:

Human brain aneurysms may often prove fatal if not re­cognized in time and treated accordingly. The understanding of development and rupture of aneurysms can significantly be improved by the application of numerical modelling, which in turn, requires the knowledge of mechanical properties of vessel wall. This study aims to identify assumed differences with respect to age, sex, spatial orientation, and rupture by utilizing detailed statistical analysis of uniaxial tensile measurements of human brain aneurysm samples, performed by the authors in a previous project.

At surgery of 42 patients, aneu­rysm fundi were cut distally to the clip. In each case, depending on size, varying number of stripes (altogether 88) were prepared and uniaxial stress-strain measurements were performed. Quantities related to the capacity, energy absorption or stiffness were determined and statistically analysed.

The number of specimens in the aneurysm sample was sufficient to establish statistical differences with respect to sex and rupture (p<0.05). No significant differences were detected in orientation, though higher values of stresses and deformations were ob­tained in the circumferential direction com­pared to the meridional direction. 

Significant differences bet­ween sexes with respect to ultimate deformations were demonstrated according to expectation, and the hypothesis on equality of energy capacity could be supported. Similarity of curves with respect to specimen orientation was also observed and ruptured aneurysm sacs tended to be smaller in size. It seems that differences and trends described in this paper are realistic and need to be applied in numerical modelling.

Study protocol of the Hungarian Longitudinal Study of Healthy Brain Aging (HuBA).

Background and purpose:

Neuro­cog­nitive aging and the associated brain diseases impose a major social and economic burden. Therefore, substantial efforts have been put into revealing the lifestyle, the neurobiological and the genetic underpinnings of healthy neurocognitive aging. However, these studies take place almost exclusively in a limited number of highly-developed countries. Thus, it is an important open question to what extent their findings may generalize to neurocognitive aging in other, not yet investigated regions. The purpose of the Hungarian Longitudinal Study of Healthy Brain Aging (HuBA) is to collect multi-modal longitudinal data on healthy neurocognitive aging to address the data gap in this field in Central and Eastern Europe.

We adapted the Australian Ima­ging, Biomarkers and Lifestyle (AIBL) study of aging study protocol to local circumstances and collected demographic, lifestyle, men­tal and physical health, medication and medical history related information as well as re­cor­ded a series of magnetic resonance imaging (MRI) data. In addition, participants were al­so offered to participate in the collection of blood samples to assess circulating in­flam­matory biomarkers as well as a sleep study aimed at evaluating the general sleep quality based on multi-day collection of subjective sleep questionnaires and whole-night elec­troencephalographic (EEG) data.

Baseline data collection has al­ready been accomplished for more than a hundred participants and data collection in the se­cond
session is on the way. The collected data might reveal specific local trends or could also indicate the generalizability of previous findings. Moreover, as the HuBA protocol al­so offers a sleep study designed for tho­rough characterization of participants’ sleep quality and related factors, our extended multi-modal dataset might provide a base for incorporating these measures into healthy and clinical aging research. 

Besides its straightforward na­tional benefits in terms of health ex­pen­di­ture, we hope that this Hungarian initiative could provide results valid for the whole Cent­ral and Eastern European region and could also promote aging and Alzheimer’s disease research in these countries.

Indications for Sleeve Gastrectomy-Is It Worth Waiting for Comorbidities to Develop?

(1) Background and Objectives: Morbid obesity significantly increases the prevalence of comorbidities, such as heart disease, restrictive lung disease, stroke, diabetes mellitus and more. (2) Methods: Patients undergoing gastric sleeve surgery were divided into three groups with BMI between 30-34.9 kg/m2 (Group I), 35-39.9 kg/m2 (Group II), and over 40 kg/m2 (Group III). Preoperative examinations included cardiac ultrasound, respiratory function and laboratory tests, and preoperative comorbidities were also recorded. Following a one-year follow-up, we compared the rate of weight loss in the three groups at six months and one year following surgery, specifically, the effect of surgery on preoperative comorbidities at one year. (3) Results: The weight loss surgeries performed were successful in all three groups. Preoperative laboratory examinations, an echocardiogram and respiratory function results showed no clinically significant difference, except moderate elevations in blood lipid levels. Hypertension was the most common comorbidity. (4) Conclusions: In our patient population, hypertension and diabetes were the only comorbidities with a high prevalence. It can be explained by the relatively younger age among the patients (mean age 44.5 years) and the fact that they had not yet developed the pathological consequences of severe obesity. Consequently, while performing the surgery at a relatively younger age, it seems far more likely that the patient will return to a more active and productive life and enjoy a better quality of life. Additionally, the perioperative risk is lower, and the burden upon health systems and health expenditure is reduced by preventing comorbidities, in particular, multimorbidity. On this basis, it may be advisable to direct patients who do not exhaust the classical indications for bariatric surgery toward the surgical solution at a younger age. Our results suggest it is not worth waiting for comorbidities, especially multimorbidity, to appear.

Poor Preoperative Nutritional Status, but Not Hormone Levels, Are Associated With Mortality After Cardiac Surgery.

OBJECTIVES: The authors' aim was to examine the preoperative hormone and nutritional status in patients undergoing elective cardiac surgery. DESIGN AND SETTINGS: The authors' research was a single-center, prospective, observational study (ClinicalTrials.gov: NCT03736499). PARTICIPANTS & INTERVENTIONS: The authors examined 252 patients who underwent elective cardiac surgery. Preoperative thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), free thyroxine (fT4), prolactin, and testosterone levels were collected and analyzed after the surgery. The Geriatric Nutritional Risk Index (GNRI), Controlling Nutritional Status (CONUT), and Prognostic Nutritional Index (PNI) were all calculated as a sum and groups. Frailty was calculated based on the modified Frailty Index-11. The primary outcome was overall mortality. MEASUREMENTS AND MAIN RESULTS: The mean age of the patients was 64.23 years (standard deviation: 11.07 years). Thirty-three patients (13.01%) died during the median follow-up time of 20.48 months (interquartile range: 18.90-22.98 months). Thyroid hormones were examined as continuous variables and also in 3 groups based on low, normal, and high hormone levels. Continuous TSH (p = 0.230), continuous fT3 (p = 0.492), and continuous fT4 (p = 0.657) were not significantly associated with total mortality. After adjustment for the European System for Cardiac Operative Risk Evaluation II and postoperative complications, the following nutritional scores were associated with total mortality: GNRI < 91 (adjusted hazard ratio [AHR]: 4.384; 95% confidence interval [CI]: 1.866-10.303, p = 0.001), the higher CONUT group (AHR: 1.736; 95% CI: 1.736-2.866, p = 0.031), and a PNI < 48 points (AHR: 3.465; 95% CI: 1.735-6.918, p < 0.001). The modified Frailty Index-11 was not associated with mortality. CONCLUSIONS: Before cardiac surgery, nutritional status should be assessed because the findings may help to decrease mortality. The hormone levels were not associated with mortality.

Transfer of complex regional pain syndrome to mice via human autoantibodies is mediated by interleukin-1-induced mechanisms.

Neuroimmune interactions may contribute to severe pain and regional inflammatory and autonomic signs in complex regional pain syndrome (CRPS), a posttraumatic pain disorder. Here, we investigated peripheral and central immune mechanisms in a translational passive transfer trauma mouse model of CRPS. Small plantar skin-muscle incision was performed in female C57BL/6 mice treated daily with purified serum immunoglobulin G (IgG) from patients with longstanding CRPS or healthy volunteers followed by assessment of paw edema, hyperalgesia, inflammation, and central glial activation. CRPS IgG significantly increased and prolonged swelling and induced stable hyperalgesia of the incised paw compared with IgG from healthy controls. After a short-lasting paw inflammatory response in all groups, CRPS IgG-injected mice displayed sustained, profound microglia and astrocyte activation in the dorsal horn of the spinal cord and pain-related brain regions, indicating central sensitization. Genetic deletion of interleukin-1 (IL-1) using IL-1αß knockout (KO) mice and perioperative IL-1 receptor type 1 (IL-1R1) blockade with the drug anakinra, but not treatment with the glucocorticoid prednisolone, prevented these changes. Anakinra treatment also reversed the established sensitization phenotype when initiated 8 days after incision. Furthermore, with the generation of an IL-1ß floxed(fl/fl) mouse line, we demonstrated that CRPS IgG-induced changes are in part mediated by microglia-derived IL-1ß, suggesting that both peripheral and central inflammatory mechanisms contribute to the transferred disease phenotype. These results indicate that persistent CRPS is often contributed to by autoantibodies and highlight a potential therapeutic use for clinically licensed antagonists, such as anakinra, to prevent or treat CRPS via blocking IL-1 actions.

The effect of cognitive dysfunction on mid- and long-term mortality after vascular surgery.

BACKGROUND: In recent decades, previous studies have noted the importance of frailty, which is a frequently used term in perioperative risk evaluations. Psychological and socioeconomical domains were investigated as part of frailty syndrome. The aim of this study was to assess the importance of these factors in mortality after vascular surgery. METHODS: In our prospective, observational study (ClinicalTrials.gov Identifier: NCT02224222), we examined 164 patients who underwent elective vascular surgery between 2014 and 2017. At the outpatient anaesthesiology clinic, patients completed a questionnaire about cognitive functions, depression and anxiety, social support and self-reported quality of life were assessed using a comprehensive frailty index, in addition to medical variables. Propensity score matching was performed to analyse the difference between patients and controls in a nationwide population cohort. The primary outcome was 4 year mortality. The Kaplan-Meier method and Cox regression analysis were used for statistical analyses. RESULTS: The patients' mean age was 67.05 years (SD: 9.49 years). Mini-Mental State Examination scores of less than 27 points were recorded for 41 patients. Overall mortality rates were 22.4 and 47.6% in the control and cognitive impairment groups, respectively (p = 0.013). In the univariate Cox regression analysis, cognitive impairment measured using age- and education-adjusted MMSE scores increased the risk of mortality (AHR: 2.842, 95% CI: 1.389-5.815, p = 0.004). CONCLUSION: Even mild cognitive dysfunction measured preoperatively using the MMSE represents a potentially important risk factor for mortality after vascular surgery.

Folate-Targeted Monodisperse PEG-Based Conjugates Made by Chemo-Enzymatic Methods for Cancer Diagnosis and Treatment.

This paper focuses on preliminary in vitro and in vivo testing of new bivalent folate-targeted PEGylated doxorubicin (DOX) made by modular chemo-enzymatic processes (FA2-dPEG-DOX2). A unique feature is the use of monodisperse PEG (dPEG). The modular approach with enzyme catalysis ensures exclusive γ-conjugation of folic acid, full conversion and selectivity, and no metal catalyst residues. Flow cytometry analysis showed that at 10 µM concentration, both free DOX and FA2-dPEG-DOX2 would be taken up by 99.9% of triple-negative breast cancer cells in 2 h. Intratumoral injection to mice seemed to delay tumor growth more than intravenous delivery. The mouse health status, food, water consumption, and behavior remained unchanged during the observation.

Awake Sedation With Propofol Attenuates Intraoperative Stress of Carotid Endarterectomy in Regional Anesthesia.

BACKGROUND: Carotid endarterectomy in regional anesthesia is often associated with increased perioperative stress. We assumed that carotid endarterectomy performed under awake sedation with propofol is more beneficial to prevent such stress than alprazolam premedication only. METHODS: A total of 47 consecutive patients with significant carotid artery stenosis were enrolled into this investigation and followed up for 5 years to explore vascular complications. All operations were performed under regional anesthesia. As premedication, all patients took 0.5 mg of alprazolam 30 minutes before the procedure. After randomization, 22 patients had awake sedation with target controlled propofol infusion, and the other 25 had only premedication. Cortisol plasma levels were serially analyzed: before surgery (T1), before (T2) and after release of carotid clamp (T3), and at 2 (T4) and 24 postoperative hours (T5). Alprazolam levels were also measured before and after the surgery. RESULTS: The plasma concentration of cortisol was significantly lower in the propofol sedation group at T2 (P < 0.001), T3 (P = 0.001), and T4 (P < 0.001) than in the alprazolam-only group. Alprazolam levels did not correlate with cortisol levels at any time point. A significant positive correlation was found between the clamp time and plasma cortisol level at T3 (P = 0.018), similarly between the degree of contralateral carotid stenosis and plasma cortisol level at T3 (P = 0.03). Plasma cortisol concentration 2 hours after the operation (T4) proved to be an independent predictor of carotid restenosis during the 5-year follow-up (odds ratio: 1.67, 95% confidence interval: 1.02-2.73, P = 0.04). CONCLUSIONS: An additional intraoperative propofol sedation provides better stress relief than alprazolam-only premedication during awake carotid endarterectomy.

The formin DAAM is required for coordination of the actin and microtubule cytoskeleton in axonal growth cones.

Directed axonal growth depends on correct coordination of the actin and microtubule cytoskeleton in the growth cone. However, despite the relatively large number of proteins implicated in actin-microtubule crosstalk, the mechanisms whereby actin polymerization is coupled to microtubule stabilization and advancement in the peripheral growth cone remained largely unclear. Here, we identified the formin Dishevelled-associated activator of morphogenesis (DAAM) as a novel factor playing a role in concerted regulation of actin and microtubule remodeling in Drosophilamelanogaster primary neurons. In vitro, DAAM binds to F-actin as well as to microtubules and has the ability to crosslink the two filament systems. Accordingly, DAAM associates with the neuronal cytoskeleton, and a significant fraction of DAAM accumulates at places where the actin filaments overlap with that of microtubules. Loss of DAAM affects growth cone and microtubule morphology, and several aspects of microtubule dynamics; and biochemical and cellular assays revealed a microtubule stabilization activity and binding to the microtubule tip protein EB1. Together, these data suggest that, besides operating as an actin assembly factor, DAAM is involved in linking actin remodeling in filopodia to microtubule stabilization during axonal growth.

Mannose-Binding Lectin Drives Platelet Inflammatory Phenotype and Vascular Damage After Cerebral Ischemia in Mice via IL (Interleukin)-1α.

Objective- Circulating complement factors are activated by tissue damage and contribute to acute brain injury. The deposition of MBL (mannose-binding lectin), one of the initiators of the lectin complement pathway, on the cerebral endothelium activated by ischemia is a major pathogenic event leading to brain injury. The molecular mechanisms through which MBL influences outcome after ischemia are not understood yet. Approach and Results- Here we show that MBL-deficient (MBL-/-) mice subjected to cerebral ischemia display better flow recovery and less plasma extravasation in the brain than wild-type mice, as assessed by in vivo 2-photon microscopy. This results in reduced vascular dysfunction as shown by the shift from a pro- to an anti-inflammatory vascular phenotype associated with MBL deficiency. We also show that platelets directly bind MBL and that platelets from MBL-/- mice have reduced inflammatory phenotype as indicated by reduced IL-1α (interleukin-1α) content, as early as 6 hours after ischemia. Cultured human brain endothelial cells subjected to oxygen-glucose deprivation and exposed to platelets from MBL-/- mice present less cell death and lower CXCL1 (chemokine [C-X-C motif] ligand 1) release (downstream to IL-1α) than those exposed to wild-type platelets. In turn, MBL deposition on ischemic vessels significantly decreases after ischemia in mice treated with IL-1 receptor antagonist compared with controls, indicating a reciprocal interplay between MBL and IL-1α facilitating endothelial damage. Conclusions- We propose MBL as a hub of pathogenic vascular events. It acts as an early trigger of platelet IL-1α release, which in turn favors MBL deposition on ischemic vessels promoting an endothelial pro-inflammatory phenotype.

Microglia control the spread of neurotropic virus infection via P2Y12 signalling and recruit monocytes through P2Y12-independent mechanisms.

Neurotropic herpesviruses can establish lifelong infection in humans and contribute to severe diseases including encephalitis and neurodegeneration. However, the mechanisms through which the brain's immune system recognizes and controls viral infections propagating across synaptically linked neuronal circuits have remained unclear. Using a well-established model of alphaherpesvirus infection that reaches the brain exclusively via retrograde transsynaptic spread from the periphery, and in vivo two-photon imaging combined with high resolution microscopy, we show that microglia are recruited to and isolate infected neurons within hours. Selective elimination of microglia results in a marked increase in the spread of infection and egress of viral particles into the brain parenchyma, which are associated with diverse neurological symptoms. Microglia recruitment and clearance of infected cells require cell-autonomous P2Y12 signalling in microglia, triggered by nucleotides released from affected neurons. In turn, we identify microglia as key contributors to monocyte recruitment into the inflamed brain, which process is largely independent of P2Y12. P2Y12-positive microglia are also recruited to infected neurons in the human brain during viral encephalitis and both microglial responses and leukocyte numbers correlate with the severity of infection. Thus, our data identify a key role for microglial P2Y12 in defence against neurotropic viruses, whilst P2Y12-independent actions of microglia may contribute to neuroinflammation by facilitating monocyte recruitment to the sites of infection.

[The start of the Hungarian lung transplantation program and the first results]. / A magyar tüdotranszplantációs program indulása és elso eredményei.

The first lung transplantation in Hungary was performed on 12th of December, 2015. It was a joint effort of the National Institute of Oncology and the Semmelweis University. Hereby we summarise the results and experiences from the first three years. Until August, 2018, 55 lung transplantations were performed in Hungary. This was a retrospective analysis. All patients were listed according to the recommendation of the Lung Transplantation Committee. All implanted lungs have been procured from brain dead donors. Postoperative treatment and rehabilitation of the patients were continued at the Semmelweis University. Between 12. 12. 2015 and 31. 07. 2018, our team performed 76 organ retrievals: out of 45 Hungarian offers, 23 came from Eurotransplant countries and 8 outside of the Eurotransplant region. From these donations, 54 double and 1 single side transplantations were successfully performed. The surgical approach was single side thoracotomy (n = 1), bilateral thoracotomy (n = 1) and in the majority of the cases clamshell incision (n = 53). For the intraoperative veno-arterial extracorporeal membrane oxygenation support was used. The extracorporeal membrane oxygenation support had to be prolonged in 3 patients into the early postoperative period, two other recipients were bridged to transplant with extracorporeal membrane oxygenation. In the same time period, one combined lung-kidney transplantation was also performed. The distribution of recipients according to the underlying disease was: chronic obstructive pulmonary disease (n = 28); idiopathic pulmonary fibrosis (n = 8); cystic fibrosis (n = 12); primary pulmonary hypertension (n = 2); hystiocytosis-X (n = 1); bronchiectasis (n = 2); lymphangioleiomyomatosis (n = 1); and re-transplantation following bronchiolitis obliterans syndrome (n = 1), respectively. The mean age of recipients was 47.5 ± 15.18 years. The youngest recipient was 13 years old. We unfortunately lost 12 patients on our waiting list. The mean intensive care unit stay was 24.6 ± 18.18 days. Two patients were lost in the early postoperative phase. Tracheostomy was necessary in 13 cases due to the need of prolonged ventilation. 1-year survival of the recipients was 82.96% (until 31. 07. 2018). When looking at the first three years of the program, the case numbers elevated quickly throughout the years which is rather unique when compared to other centres in their starting period. Perioperative mortality and morbidity is comparable with high-volume lung transplantation centres. In the future we would like to increase the number of patients on the waiting list, thus increasing the total number of transplantations performed, and we are also planning to implement the use of the ex vivo lung perfusion system (EVLP) in our program. Orv Hetil. 2018; 159(46): 1859-1868.

Cerebrovascular dysregulation and postoperative cognitive alterations after carotid endarterectomy.

There are controversial data about the effect of carotid endarterectomy regarding postoperative cognitive function. Our aim was to analyze the effect of cerebral tissue saturation monitored by near-infrared spectroscopy (NIRS) on cognitive function. Perioperative data of 103 asymptomatic patients undergoing elective carotid surgery under general anesthesia were analyzed. Preoperatively and 3 months after the operation, MMSE (Mini Mental State Examination) and MoCA (Montreal Cognitive Assessment) tests were conducted. For cerebral monitoring, NIRS was used, and the lowest rSO2 value and the degree of desaturation were calculated. Cognitive changes were defined as one standard deviation change from the preoperative test scores, defined as postoperative neurocognitive decline (PNCD) and cognitive improvement (POCI). PNCD was found in 37 patients (35.92%), and POCI was found in 18 patients (17.47%). Female gender, patients with diabetes, and the degree of desaturation were independently associated with PNCD. The degree of desaturation during the cross-clamp period negatively correlated with the change in the MoCA scores (R = - 0.707, p = 0.001). The 15.5% desaturation ratio had 86.5% sensitivity and 78.8% specificity for discrimination. For POCI, a desaturation of less than 12.65% had 72.2% sensitivity and 67.1% specificity. POCI was associated with lower preoperative MOCA scores and a lower degree of desaturation. We found a significant relation between the change of postoperative cognitive function proven by the MoCA test and cerebral tissue saturation during the clamping period in patients undergoing carotid endarterectomy.

Engagement of medication users in the development and implementation of digital medication adherence technologies: a multi-stakeholder study.

BACKGROUND: This study aims to create a comprehensive framework for the development and implementation of digital medication adherence technologies (DMATech), focusing on critical stages where engagement of medication users (MU) is considered meaningful, i.e. adds significant value, as agreed upon by participating stakeholders. METHODS: Through a literature review and expert consensus, a framework was outlined covering key DMATech development and implementation phases and steps. An in-person workshop with MU representatives and adherence experts, using the Nominal Group Technique, further refined these stages for MU engagement. RESULTS: The DMATech framework included three phases: 'Innovation,' 'Research and Development,' and 'Launch and Implementation,' each encompassing multiple steps. The workshop, attended by five MU representatives and nine adherence experts, identified critical stages for MU input including context analysis, ideation, proof of concept, prototype creation, DMATech's iteration, critical evaluation, healthcare implementation, real-world assessment, and improvement. Nevertheless, there was a divergence of consensus regarding the importance of MUs engagement in regulatory, financial, and marketing aspects. CONCLUSIONS: This study provides a holistic framework for DMATech development and implementation and underscores the necessity of MU engagement at various stages. Modes of MU engagement cannot be generalized; a case-by-case evaluation of engagement strategies is essential.

Electrospun polysuccinimide scaffolds containing different salts as potential wound dressing material.

In this research, we applied electrospinning to create a two-component biodegradable polymeric scaffold containing polysuccinimide (PSI) and antibacterial salts. Antibacterial agents for therapeutical purposes mostly contain silver ions which are associated with high environmental impact and, in some cases, may cause undesired immune reactions. In our work, we prepared nanofibrous systems containing antibacterial and tissue-regenerating salts of zinc acetate or strontium nitrate in different concentrations, whose structures may be suitable for developing biomedical wound dressing systems in the future. Several experiments have been conducted to optimize the physicochemical, mechanical, and biological properties of the scaffolds developed for application as wound dressings. The scaffold systems obtained by PSI synthesis, salt addition, and fiber formation were first investigated by scanning electron microscopy. In almost all cases, different salts caused a decrease in the fiber diameter of PSI polymer-based systems (<500 nm). Fourier-transform infrared spectroscopy was applied to verify the presence of salts in the scaffolds and to determine the interaction between the salt and the polymer. Another analysis, energy-dispersive X-ray spectroscopy, was carried out to determine strontium and zinc atoms in the scaffolds. Our result showed that the salts influence the mechanical properties of the polymer scaffold, both in terms of specific load capacity and relative elongation values. According to the dissolution experiments, the whole amount of strontium nitrate was dissolved from the scaffold in 8 h; however, only 50% of the zinc acetate was dissolved. In addition, antibacterial activity tests were performed with four different bacterial strains relevant to skin surface injuries, leading to the appearance of inhibition zones around the scaffold discs in most cases. We also investigated the potential cytotoxicity of the scaffolds on human tumorous and healthy cells. Except for the ones containing zinc acetate salt, the scaffolds are not cytotoxic to either tumor or healthy cells.

[Acute pancreatitis after cesarean section]. / Akut hasnyálmirigy-gyulladás császármetszést követoen.

The prevalence of acute pancreatitis in pregnancy is low; similarly to the non-pregnant population, the outcome varies from mild to fatal forms. Occurrence of the disease in pregnancy is mostly in the third trimester or the postpartum period. The most common cause of acute pancreatitis is cholelithiasis but hypertriglyceridemia, fatty diet, obesity and alcohol consumption are further predisposing factors. A 27-year-old twin-pregnant woman developed acute severe pain 2 days after a cesarean section. Labor tests showed elevated amylase (1080 U/L) and lipase (2670 U/L) serum levels. For the purpose of pain relief, we inserted an epidural catheter and indicated an abdominal computer tomography examination. The abdominal imaging did not show morphological disorder of the pancreas or cholangial obstruction. We performed conservative therapy, early per os feeding, pain relief and fluid resuscitation. On the postpartum 7. day, the serum pancreas enzyme levels decreased to normal and the patient - with her babies - was discharged home. Though acute pancreatitis is a rare event in pregnancy, we should consider it in cases with acute, typical or non-typical pain. It is challenging to differentiate the disease from the acute syndromes of pregnancy. Orv Hetil. 2023; 164(31): 1231-1234.

[Efficacy of laparoscopic sleeve gastrectomy on morbidly obese patients]. / Kórosan elhízott betegeken végzett laparoszkópos csogyomorképzés eredményességének vizsgálata.

INTRODUCTION: Obesity is a modern-day epidemic that places a significant and growing burden on the health systems of societies and their financial resources. OBJECTIVE: Our prospective, descriptive clinical study aimed to investigate the effect of laparoscopic gastric sleeve surgery in morbidly obese patients through a one-year follow-up. METHOD: In our study, we included 151 patients who underwent laparoscopic gastric sleeve surgery. We performed cardiac ultrasound, respiratory function and laboratory tests for pre-operative examination, possible co-morbidities were assessed, and the parameters of morbid obesity were also recorded, before surgery, half a year and one year after. RESULTS: Patients' body mass index decreased by 26.9% in the first six months and by 35.4% overall at one year, and body fat percentage decreased by 26.2% and 35%, respectively, over the same time intervals. The average age of patients was 41 years. Pre-operative cardiac ultrasound, respiratory function and laboratory tests showed no significant pathological abnormalities and a low rate of co-morbidities were associated with obesity (hypertension 51.7%, type two diabetes mellitus 13.8%). DISCUSSION: Based on the one-year follow-up data, the surgery was effective in weight loss, but long-term results can be expected at the five-year assessment, as there is a risk of repeated weight gain. Based on our study, in the case of failure of conservative treatment, it is recommended to perform the surgery at a young age, achieving the appropriate weight loss before the appearance or further aggravation of co-morbidities. Thus, the perioperative risk (and the probability of the subsequent development or further deterioration of co-morbidities) will decrease; conversely, the number of years spent in a better quality of life will increase. CONCLUSION: Laparoscopic sleeve gastrectomy is an effective weight loss procedure in the short term. If conservative treatment is ineffective, it is worthwhile to steer the patient towards invasive procedures as soon as possible to reduce the perioperative risk and the number of years spent in poor quality of life. Orv Hetil. 2023; 164(44): 1749-1754.