Successful Implementation of HITOC and HIPEC in the Management of Advanced Ovarian Carcinoma with Pleural and Peritoneal Carcinomatosis.

This case report details the application and outcomes of a novel therapeutic approach involving hyperthermic intraperitoneal chemotherapy (HIPEC) and hyperthermic intrathoracic chemotherapy (HITOC) in a single patient diagnosed with advanced ovarian neoplasm. The treatment protocol included pleural cytoreductive surgery (CRS) and HITOC followed by a second surgical intervention consisting of peritoneal CRS and HIPEC. HIPEC targeted the intraperitoneal space with heated chemotherapy, while HITOC extended the thermal perfusion to the thoracic cavity. The patient has shown significant progression in disease-free survival over one year and eight months of observation, demonstrating lower recurrence rates and an overall survival outcome exceeding expectations based on conventional therapy outcomes. The combined modality demonstrated a manageable toxicity profile, with no significant increase in peri- or postoperative complications observed.

Generalized polarization and time-resolved fluorescence provide evidence for different populations of Laurdan in lipid vesicles.

The solvatochromic dye Laurdan is widely used in sensing the lipid packing of both model and biological membranes. The fluorescence emission maximum shifts from about 440 nm (blue channel) in condensed membranes (So) to about 490 nm (green channel) in the liquid-crystalline phase (Lα). Although the fluorescence intensity based generalized polarization (GP) is widely used to characterize lipid membranes, the fluorescence lifetime of Laurdan, in the blue and the green channel, is less used for that purpose. Here we explore the correlation between GP and fluorescence lifetimes by spectroscopic measurements on the So and Lα phases of large unilamellar vesicles of DMPC and DPPC. A positive correlation between GP and the lifetimes is observed in each of the optical channels for the two lipid phases. Microfluorimetric determinations on giant unilamellar vesicles of DPPC and DOPC at room temperature are performed under linearly polarized two-photon excitation to disentangle possible subpopulations of Laurdan at a scale below the optical resolution. Fluorescence intensities, GP and fluorescence lifetimes depend on the angle between the orientation of the linear polarization of the excitation light and the local normal to the membrane of the optical cross-section. This angular variation depends on the lipid phase and the emission channel. GP and fluorescence intensities in the blue and green channel in So and in the blue channel in Lα exhibit a minimum near 90o. Surprisingly, the intensity in the green channel in Lα reaches a maximum near 90o. The fluorescence lifetimes in the two optical channels also reach a pronounced minimum near 90o in So and Lα, apart from the lifetime in the blue channel in Lα where the lifetime is short with minimal angular variation. To our knowledge, these experimental observations are the first to demonstrate the existence of a bent conformation of Laurdan in lipid membranes, as previously suggested by molecular dynamics calculations.

Safety of Innovative Nanotechnology Oral Formulations Loaded with Bioactive Menopause Molecules: Influence of Genotoxicity and Biochemical Parameters on a Menopausal Rat Model.

In recent years, nanoparticles have gained significant importance due to their unique properties, such as pharmacological, electrical, optical, and magnetic abilities, contributing to the growth of the science and technology sector. Particular naturally derived biomolecules with beneficial effects on menopause disorder have been the subject of studies of pharmaceutical formulation to obtain alternative pharmaceutical forms with increased bioavailability and without side effects, as in nanostructured lipid carriers (NLCs) loaded with such active ingredients. In the present study, one stage of a broader project, we have performed pharmacotoxicology studies for six combinatory innovative nanocapsule pharmaceutical forms containing active natural biomolecules before considering them as oral formulas for (1) in vitro toxicity studies on culture cells and (2) in vivo preclinical studies on a surgically induced menopause model of Wistar female rats, and the influence of the NLCs on key biochemical parameters: lipid profile (TG, Chol, HDL), glycemic markers (Gli), bone markers (Pac, Palc, Ca, phosphorus), renal markers (Crea, urea, URAC), inflammation (TNF), oxidative stress (GSH, MDA), and estrogen-progesterone hormonal profile. The micronucleus test did not reveal the genotoxicity of the tested compounds; the menopause model showed no significant safety concerns for the six tested formulas evaluated using the blood biochemical parameters; and the results showed the potential hypoglycemic, hypolipidemic, hypouricemic, and antioxidant potential of one of the tested formulas containing nano diosgenin and glycyrrhizic acid.

Cetirizine and Levetiracetam as Inhibitors of Monoacylglycerol Lipase: Investigating Their Repurposing Potential as Novel Osteoarthritic Pain Therapies.

Osteoarthritis is characterized by progressive articular cartilage degradation, subchondral bone changes, and synovial inflammation, and affects various joints, causing pain and disability. Current osteoarthritis therapies, primarily focused on pain management, face limitations due to limited effectiveness and high risks of adverse effects. Safer and more effective treatments are urgently needed. Considering that the endocannabinoid 2-arachidonoyl glycerol is involved in pain processing, increasing its concentration through monoacylglycerol lipase (MAGL) inhibition reduces pain in various animal models. Furthermore, drug repurposing approaches leverage established drug safety profiles, presenting a cost-effective route to accelerate clinical application. To this end, cetirizine and levetiracetam were examined for their MAGL inhibitory effects. In vitro studies revealed that cetirizine and levetiracetam inhibited MAGL with IC50 values of 9.3931 µM and 3.0095 µM, respectively. In vivo experiments demonstrated that cetirizine, and to a lesser extent levetiracetam, reduced mechanical and thermal nociception in complete Freund adjuvant (CFA)-induced osteoarthritis in rats. Cetirizine exhibited a notable anti-inflammatory effect, reducing CFA-induced inflammation, as well as the inflammatory infiltrate and granuloma formation in the affected paw. These findings suggest that cetirizine may serve as a promising starting point for the development of novel compounds for osteoarthritis treatment, addressing both pain and inflammation.

Risk factors for involuntary admission in a Romanian patient sample.

BACKGROUND: Involuntary admission is widely used in psychiatry, usually requiring that the patient present an imminent danger to himself or others. Previous studies have established several predictors for involuntary admission, but they have been almost exclusively conducted in Western European or North American countries. By contrast, data on this topic from Eastern European countries is virtually absent. Historically, involuntary admission has been often used as a tool for political repression in Romania before the fall of the communist regime. While there have been significant changes in the legal framework in the last 30 years, there is still no real-world data to build upon. METHODS: We analyzed a sample of 177 patients admitted to the "Alexandru Obregia" psychiatric hospital in Bucharest between November 2022 and January 2023, of which 49.7% (88) were involuntary hospitalizations. We collected socio-demographic and clinical data by both by direct interview, and by consulting patient records, attending physicians and relatives. RESULTS: Socio-demographic factors predictive for involuntary admission were unemployment, lower income, and urban living. Of the clinical variables analyzed, diagnosis of psychosis or mania on admission carried increased risk of involuntary hospitalization, as did nonadherence to treatment, higher disease severity and aggression. Hospital presentation by police or ambulance carried significant additional risk compared to self-referral. CONCLUSION: Certain categories of patients are considerably more likely to be involuntarily hospitalized and there appears to be considerable interrelatedness between the identified risk factors.

Cationic exchange SPE combined with triple quadrupole UHPLC-MS/MS for detection of GHRHs in urine samples.

The use of growth hormone-releasing hormones (GHRHs) is prohibited in sports according to the regulations of the World Anti-Doping Agency (WADA). Considering the complexity of urine samples and the low concentrations at which these analytes should be detected, analyzing GHRHs is a challenging task. In most of the studies, GHRHs are analyzed using UHPLC-HRMS with an orbitrap. The present developed and validated method for some GHRHs (tesamorelin, CJC-1295, sermorelin (GRF 1-29), sermorelin (3-29)-NH2, somatorelin) is based on the triple quadrupole UHPLC/MS-MS method with solid phase extraction (SPE) with weak cation exchange and is able to detect concentrations as low as 0.2 ng/mL (LOD), a limit of quantification (LOQ) at 0.6 ng/mL, and linearity across the range of 0.1 ng/mL to 1.2 ng/mL. The present method developed by our doping control laboratory was validated according to WADA technical documents for selectivity, limit of detection (LOD), carryover, reliability of detection, stability and recovery. The results show that the method has adequate recoveries and sensitivity, hence, it can be employed for routine screening in anti-doping laboratories.

The Impact of Acute Low-Dose Gamma Irradiation on Biomass Accumulation and Secondary Metabolites Production in Cotinus coggygria Scop. and Fragaria × ananassa Duch. Red Callus Cultures.

Cotinus coggygria Scop. (smoketree) and Fragaria × ananassa Duch. (strawberry) are two industrially important species due to their composition in bioactive compounds. In this study, we investigated the effects of acute low-dose gamma irradiation (15, 20, 25, 30, 35 and 40 Gy) on two red callus cultures established in smoketree and strawberry. The biomass production, dry weight, content of phenols, flavonoids, monomeric anthocyanins', index of anthocyanins polymerization and antioxidant activity were evaluated. For the smoketree callus, a negative correlation between irradiation doses and callus biomass accumulation was observed. For the strawberry callus, irradiation did not significantly affect the accumulation of the biomass. An increased dry weight was observed in irradiated smoketree callus, while for treated strawberry callus, a decrease was recorded. Irradiation with 30 Gy was stimulative for polyphenols' accumulation in both cultures; however, the increase was significant only in the strawberry callus. The flavonoids increased in the 30 Gy strawberry variants, while it significantly decreased in smoketree callus irradiated with 35 and 40 Gy. In irradiated strawberry callus, except for the 25 Gy variant (1.65 ± 0.4 mg C-3-GE/g DW), all treatments caused an increase in anthocyanins' accumulation. In smoketree, except for the 15 Gy variant (2.14 ± 0.66 mg C-3-GE/g DW), the irradiation determined an increase in anthocyanins synthesis, with the highest value being seen in the 20 Gy variant (2.8 ± 0.94 mg C-3-GE/g DW). According to UPLC-HRMS investigations, an unidentified compound increased by 99% at the 30 Gy dose in strawberry callus, while in smoketree, maslinic acid increased by 51% after irradiation with 40 Gy. The results of this study showed, for the first time, the differential response of two performant callus cultures to low-dose gamma irradiation, a biotechnological method that can be used to stimulate the synthesis of important flavonoids and triterpenes.

Non-Pharmacological Interventions for Pain Management in Hemodialysis: A Narrative Review.

This narrative review aims to summarize non-pharmacological interventions for pain management in hemodialysis patients, assessing their potential benefits and limitations in enhancing patient well-being and quality of life. We reviewed the current literature on five primary non-pharmacological interventions: acupuncture, cognitive behavioral therapy, relaxation techniques, virtual reality, and alternative methods such as transcutaneous electrical nerve stimulation, music therapy, and aromatherapy. We analyzed the evidence regarding their effectiveness, feasibility, and optimal implementation strategies. The existing evidence supports the potential benefits of these interventions in managing pain and improving the well-being of hemodialysis patients. However, further high-quality research is needed to confirm their effectiveness, establish implementation best practices, and assess their long-term impact on patient outcomes. Non-pharmacological interventions hold promise for pain management in hemodialysis patients. Additional research is required to optimize these interventions and validate their effectiveness, contributing to comprehensive pain management strategies for this vulnerable patient population.

Dropout and compliance to physical exercise in menopausal osteopenic women: the European "happy bones" project.

Introduction: Decline in muscle mass and bone density seem to be two of the most disabling side effects of menopause that negatively affect women's quality of life. Promoting physical activity protocols in the workplace can represent a focal point in the prevention and management of several diseases. The study aims to evaluate the compliance and drop-out of menopausal osteopenic women engaged in combined training performed inside and outside the workplace. Strength and balance were analyzed to evaluate the effect of this protocol on osteoporosis prevention and the risk of falling. Methods: 73 menopausal women were enrolled in 5 European countries. They performed 72 lessons of a combined training proposed in the working place (IW) or sport center (SC). Results: Out of the total 39 women enrolled in the IW, 12.8% had to leave the program, while out of the 34 women enrolled in SC, 41.2% did not complete the training. According to the compliance results, 47% of women that completed the trained IW and 85% in the SC recorded high compliance (p = 0.019). Moreover, the strength of the lower limbs (p < 0.001) and static balance (p = 0.001) significantly improved in the whole group. Discussion: In conclusion, proposing well-structured training in the workplace for menopausal women seems to reduce drop-out. Strength and balance results suggest its positive impact on bone health and risk of falls, despite where it is performed.

Transperineal Prostate Biopsy Targeted by Magnetic Resonance Imaging Cognitive Fusion.

Prostate cancer is among the most frequently diagnosed cancers and a leading cause of cancer-related death in men. Currently, the most reliable and widely used imaging test for prostate cancer diagnosis is multiparametric pelvic magnetic resonance imaging (mpMRI). Modern biopsy techniques are based on the computerised merging of ultrasound and MRI images to provide better vision during the biopsy procedure (Fusion Biopsy). However, the method is expensive due to high equipment cost. Cognitive fusion of ultrasound and MRI images has recently emerged as a cheaper and easier alternative to computerised fusion. The aim of this prospective study is to perform an in-patient comparison of the systematic prostate biopsy procedure (SB) vs. cognitive fusion (CF) guided prostate biopsy method in terms of safety, ease of use, cancer detection rate and clinically significant cancer detection. We enrolled 103 patients with suspected prostate cancer that were biopsy naive, with PSA > 4 ng/dL and PIRADS score of 3, 4 or 5. All patients received a transperineal standard 12-18 cores systematic biopsy (SB) and a four-cores targeted cognitive fusion (CF) biopsy. Following the prostate biopsy, 68% of the patients were diagnosed with prostate cancer (70/103 patients). SB diagnosis rate was 62% while CF biopsy was slightly better with a 66% rate. There was a significant 20% increase in clinically significant prostate cancer detection rate for the CF compared to SB (p < 0.05) and a significant prostate cancer risk upgrade from the low to the intermediate risk category (13%, p = 0.041). Transperineal cognitive fusion targeted prostate biopsy is a straightforward biopsy method that is easy to perform and is a safe alternative to standard systematic biopsy with improved significant cancer detection accuracy. A combined targeted and systematic approach should be used for the best diagnostic results.

Inferior Vena Cava (IVC) Resections without Reconstruction in Renal Tumors: Two Case Reports.

(1) Background: We aim to present our experience with resection of the inferior vena cava (IVC) without reconstruction in two patients diagnosed with renal tumors. (2) Case Report: The first case was diagnosed with right renal vein sarcoma and the second case was diagnosed with clear cell renal carcinoma; both presented signs of invasion and thrombosis of the IVC at infrarenal and cruoric levels, along with the development of collateral circulation with the help of the paravertebral plexus. In both patients, en bloc right nephrectomy was performed along with the resection of the thrombosed IVC without further reconstruction. In the case of the patient with right vein sarcoma, preservation of the left renal and caval intrahepatic vein was possible, whilst in the second case diagnosed with clear cell renal carcinoma, the associated left renal thrombosis also enforced the resection of the left renal vein. (3) Discussion: Postoperative evolution was favorable in both cases and did not exhibit major complications. Antibiotic therapy, analgesics, and anticoagulant medication were administered at therapeutic doses after surgery in both cases. The histopathological examination of the surgical specimen confirmed the diagnoses of renal vein sarcoma in the first case and clear cell renal carcinoma in the second case. Surgical treatment and adjuvant chemotherapy prolonged survival for two years for the first case and for two months, up until this moment, for the second case. The survival of clear cell renal carcinoma is currently at two months. (4) Conclusions: The resection of the inferior vena cava, without subsequent reconstruction in cases presenting diffused distal thrombosis, can represent an alternative to IVC reconstruction, which might lead to a major ulterior risk of thrombosis. In some cases, this can result in long-term survival.

Coping Mechanisms during the War in Ukraine: A Cross-Sectional Assessment among Romanian Population.

On 24 February 2022, the Russian Federation invaded Ukraine, starting a military conflict that soon turned into a full-scale war. The Romanians have been actively involved in helping their neighbors, causing the accumulation of emotional and mental pressure upon the Romanian population exposed to such a close military conflict. This cross-sectional study assessed, through an online survey (1586 adult Romanian residents), the primary coping mechanisms, quality of life and anxiety levels in response to the psychological trauma associated with the Russo-Ukrainian war. Based on the results, focusing on and venting emotions along with behavioral disengagement were the coping strategies that had the strongest negative impact on anxiety and well-being. On the other hand, positive reinterpretation and growth were associated with less anxiety, a higher degree of overall health and better quality of life. To the best of our knowledge, this study is the first of its kind to be performed among the Romanian population so far. Thus, we equip mental health practitioners with the tools (real-life evidence data) that will allow them to establish a more meaningful doctor-patient relationship, maximizing therapy results.

Interaction of Tryptophan- and Arginine-Rich Antimicrobial Peptide with E. coli Outer Membrane-A Molecular Simulation Approach.

A short antimicrobial peptide (AMP), rich in tryptophan and arginine (P6-HRWWRWWRR-NH2), was used in molecular dynamics (MD) simulations to investigate the interaction between AMPs and lipopolysaccharides (LPS) from two E. coli outer membrane (OM) membrane models. The OM of Gram-negative bacteria is an asymmetric bilayer, with the outer layer consisting exclusively of lipopolysaccharide molecules and the lower leaflet made up of phospholipids. The mechanisms by which short AMPs permeate the OM of Gram-negative bacteria are not well understood at the moment. For this study, two types of E. coli OM membrane models were built with (i) smooth LPS composed of lipid A, K12 core and O21 O-antigen, and (ii) rough type LPS composed of lipid A and R1 core. An OmpF monomer from E. coli was embedded in both membrane models. MD trajectories revealed that AMP insertion in the LPS layer was facilitated by the OmpF-created gap and allowed AMPs to form hydrogen bonds with the phosphate groups of inner core oligosaccharides. OM proteins such as OmpF may be essential for the permeation of short AMPs such as P6 by exposing the LPS binding site or even by direct translocation of AMPs across the OM.

Proton irradiation induced reactive oxygen species promote morphological and functional changes in HepG2 cells.

The increased use of proton therapy has led to the need of better understanding the cellular mechanisms involved. The aim of this study was to investigate the effects induced by the accelerated proton beam in hepatocarcinoma cells. An existing facility in IFIN-HH, a 3 MV Tandetron™ accelerator, was used to irradiate HepG2 human hepatocarcinoma cells with doses between 0 and 3 Gy. Colony formation was used to assess the influence of radiation on cell long-term replication. Also, the changes induced at the mitochondrial level were shown by increased ROS and ATP levels as well as a decrease in the mitochondrial membrane potential. An increased dose has induced DNA damages and G2/M cell cycle arrest which leads to caspase 3/7 mediated apoptosis and senescence induction. Finally, the morphological and ultrastructural changes were observed at the membrane level and the nucleus of the irradiated cells. Thus, proton irradiation induces both morphological and functional changes in HepG2 cells.

Risk factors and consequences of traumatic brain injury in a Swiss male population cohort.

OBJECTIVE: To investigate the risk factors for and the consequences (ie, substance use disorders (SUD), depression, personality traits) of traumatic brain injury (TBI) in young Swiss men. DESIGN: This is a three-wave cohort study. Risk factors were measured at baseline (2010-2012) and at follow-up 1 (FU1; 2012-2014), while the consequences and TBI were measured at follow-up 2 (FU2; 2016-2018). SETTING: Switzerland. PARTICIPANTS: All participants at FU2 (Mage=25.43, SD=1.25) of the Cohort Study on Substance Use Risk Factors (N=4881 young Swiss men after listwise deletion). MEASURES: The outcomes measured were TBI, SUD (ie, alcohol, nicotine, cannabis, other illicit drugs), depression and personality traits (ie, sensation seeking, anxiety-neuroticism, sociability, aggression-hostility) at FU2. The predictors were previous TBI (lifetime TBI but not in the past 12 months at FU2), SUD, personality traits and sociodemographics (highest level of achieved education, age, linguistic region) measured at FU1. RESULTS: At FU2, 3919 (80.3%) participants reported to never have had TBI, 102 (2.1%) have had TBI in the last 12 months (TBI new cases), and 860 (17.6%) have had TBI during their lifetime but not in the 12 months preceding FU2 (previous TBI). Low educational attainment (OR=3.93, 95% CI 2.10 to 7.36), depression (OR=2.87, 95% CI 1.35 to 6.11), nicotine dependence (OR=1.72, 95% CI 1.09 to 2.71), high sociability (OR=1.18, 95% CI 1.07 to 1.30), high aggression-hostility (OR=1.15, 95% CI 1.06 to 1.26) and high sensation seeking (OR=1.33, 95% CI 1.04 to 1.68) at FU1 were significantly associated with TBI new cases at FU2. Previous TBI was significantly associated with nicotine dependence (OR=1.46, 95% CI 1.16 to 1.83), depression (OR=2.16, 95% CI 1.56 to 2.99) and aggression-hostility (B=0.14, 95% CI >0.00 to 0.28) at FU2. CONCLUSION: Low educational attainment and depression are the most significant risk factors associated with increased odds of future TBI, while depression, nicotine dependence and high aggression-hostility are the main consequences of previous TBI. TBI should be considered an underlying factor in the treatment of depression, SUD or unfavourable personality profiles.

Mechanism of Caspase-1 Inhibition by Four Anti-inflammatory Drugs Used in COVID-19 Treatment.

The inflammatory protease caspase-1 is associated with the release of cytokines. An excessive number of cytokines (a "cytokine storm") is a dangerous consequence of COVID-19 infection and has been indicated as being among the causes of death by COVID-19. The anti-inflammatory drug colchicine (which is reported in the literature to be a caspase-1 inhibitor) and the corticosteroid drugs, dexamethasone and methylprednisolone, are among the most effective active compounds for COVID-19 treatment. The SERM raloxifene has also been used as a repurposed drug in COVID-19 therapy. In this study, inhibition of caspase-1 by these four compounds was analyzed using computational methods. Our aim was to see if the inhibition of caspase-1, an important biomolecule in the inflammatory response that triggers cytokine release, could shed light on how these drugs help to alleviate excessive cytokine production. We also measured the antioxidant activities of dexamethasone and colchicine when scavenging the superoxide radical using cyclic voltammetry methods. The experimental findings are associated with caspase-1 active site affinity towards these compounds. In evaluating our computational and experimental results, we here formulate a mechanism for caspase-1 inhibition by these drugs, which involves the active site amino acid Cys285 residue and is mediated by a transfer of protons, involving His237 and Ser339. It is proposed that the molecular moiety targeted by all of these drugs is a carbonyl group which establishes a S(Cys285)-C(carbonyl) covalent bond.

Prognostic Factors Influencing Survival and a Treatment Pattern Analysis of Conventional Palliative Radiotherapy for Patients with Bone Metastases.

BACKGROUND: Treatment indication for bone metastases is influenced by patient prognosis. Single-fraction radiotherapy (SFRT) was proven equally effective as multiple fractionation regimens (MFRT) but continues to be underused. OBJECTIVE: Primary objectives: (a) to identify prognostic factors for overall survival and (b) to analyze treatment patterns of palliative radiotherapy (proportion of SFRT indication and predictive factors of radiotherapy regimen) for bone metastases. METHODS: 582 patients with bone metastases who underwent conventional radiotherapy between January 1st 2014-31 December 2017 were analyzed. The Cox proportional hazard model was used to identify predictors of overall survival. For the treatment pattern analysis, 677 radiotherapy courses were evaluated. The logistic regression model was used to identify potential predictors of radiotherapy regimen. RESULTS: The 3-year overall survival was 15%. Prognostic factors associated with poor overall survival were multiple bone metastases [hazard ratio (HR = 5.4)], poor performance status (HR = 1.5) and brain metastases (HR = 1.37). SFRT prescription increased from 41% in 2017 to 51% in 2017. Predictors of SFRT prescription were a poor performance status [odds ratio (OR = 0.55)], lung (OR = 0.49) and urologic primaries (OR = 0.33) and the half-body lower site of irradiation (OR = 0.59). Spinal metastases were more likely to receive MFRT (OR = 2.09). CONCLUSIONS: Based on the prognostic factors we identified, a selection protocol for patients candidates for palliative radiotherapy to bone metastases could be established, in order to further increase SFRT prescription in our institution.

Lab-on-a-Chip Platforms as Tools for Drug Screening in Neuropathologies Associated with Blood-Brain Barrier Alterations.

Lab-on-a-chip (LOC) and organ-on-a-chip (OOC) devices are highly versatile platforms that enable miniaturization and advanced controlled laboratory functions (i.e., microfluidics, advanced optical or electrical recordings, high-throughput screening). The manufacturing advancements of LOCs/OOCs for biomedical applications and their current limitations are briefly discussed. Multiple studies have exploited the advantages of mimicking organs or tissues on a chip. Among these, we focused our attention on the brain-on-a-chip, blood-brain barrier (BBB)-on-a-chip, and neurovascular unit (NVU)-on-a-chip applications. Mainly, we review the latest developments of brain-on-a-chip, BBB-on-a-chip, and NVU-on-a-chip devices and their use as testing platforms for high-throughput pharmacological screening. In particular, we analyze the most important contributions of these studies in the field of neurodegenerative diseases and their relevance in translational personalized medicine.

Ca2+ homeostasis in brain microvascular endothelial cells.

Blood brain barrier (BBB) is formed by the brain microvascular endothelial cells (BMVECs) lining the wall of brain capillaries. Its integrity is regulated by multiple mechanisms, including up/downregulation of tight junction proteins or adhesion molecules, altered Ca2+ homeostasis, remodeling of cytoskeleton, that are confined at the level of BMVECs. Beside the contribution of BMVECs to BBB permeability changes, other cells, such as pericytes, astrocytes, microglia, leukocytes or neurons, etc. are also exerting direct or indirect modulatory effects on BBB. Alterations in BBB integrity play a key role in multiple brain pathologies, including neurological (e.g. epilepsy) and neurodegenerative disorders (e.g. Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis etc.). In this review, the principal Ca2+ signaling pathways in brain microvascular endothelial cells are discussed and their contribution to BBB integrity is emphasized. Improving the knowledge of Ca2+ homeostasis alterations in BMVECa is fundamental to identify new possible drug targets that diminish/prevent BBB permeabilization in neurological and neurodegenerative disorders.

Time Trends Analysis of Cervical Cancer Incidence in Cluj County, Romania, Using Data from a Population-Based Cancer Registry.

(1) Background: Romania has one of the highest cervical cancer incidence rates in Europe. In Cluj County, the first screening program was initiated in 1998. We aimed to investigate the time trends of cervical cancer incidence in women from Cluj County and to evaluate the data quality at the Cancer Registry. (2) Methods: We calculated time trends of standardized incidence rates in the period 1998-2014 and the Annual Percent Change (APC%). To assess data quality, we used the indicators: mortality/incidence ratio (M/I), percentage of cases declared only at death (DOD%), and percentage of cases with pathological confirmation (PC%). (3) Results: The standardized incidence rate increased steadily, from 23.74 cases/100,000 in 1998, to 32/100,000 in 2014, with an APC% of 2.49% (p < 0.05). The rise in incidence affected both squamous cell carcinoma (APC% 2.49%) (p < 0.05) and cervical adenocarcinoma (APC% 10.54%) (p < 0.05). The M/I ratio was 0.29, DOD% 2.66%, and MC% 94.8%. The last two parameters are within the silver standard concerning data quality. (4) Conclusions. Our study revealed an ascending trend of cervical cancer incidence, more consistent for adenocarcinoma, in the context of a newly introduced screening program and partially due to the improvement of the quality of case reporting at the Cancer Registry from Cluj.