Insights into yeast response to chemotherapeutic agent through time series genome-scale metabolic models.

Organism-specific genome-scale metabolic models (GSMMs) can unveil molecular mechanisms within cells and are commonly used in diverse applications, from synthetic biology, biotechnology, and systems biology to metabolic engineering. There are limited studies incorporating time-series transcriptomics in GSMM simulations. Yeast is an easy-to-manipulate model organism for tumor research. Here, a novel approach (TS-GSMM) was proposed to integrate time-series transcriptomics with GSMMs to narrow down the feasible solution space of all possible flux distributions and attain time-series flux samples. The flux samples were clustered using machine learning techniques, and the clusters' functional analysis was performed using reaction set enrichment analysis. A time series transcriptomics response of Yeast cells to a chemotherapeutic reagent-doxorubicin-was mapped onto a Yeast GSMM. Eleven flux clusters were obtained with our approach, and pathway dynamics were displayed. Induction of fluxes related to bicarbonate formation and transport, ergosterol and spermidine transport, and ATP production were captured. Integrating time-series transcriptomics data with GSMMs is a promising approach to reveal pathway dynamics without any kinetic modeling and detects pathways that cannot be identified through transcriptomics-only analysis. The codes are available at https://github.com/karabekmez/TS-GSMM.

Observation of magnet-induced star-like radiation of a plasma created from cancer cells in a laser trap.

We present a new phenomenon resulting from the interaction of magnetic beads with cancer cells in a laser trap formed on a slide containing a depression 16.5 mm in diameter and 0.78 mm of maximum depth. This phenomenon includes the apparent formation and expansion of a dark bubble that attracts and incinerates surrounding matter when it explodes, which leads to a plasma emitting intense radiation that has the appearance of a star on a microscopic scale. We have observed the star-like phenomenon for more than 4 years, and the intensity depends on the laser's power. Measuring the laser power of the dark bubble shows the entrapment of electromagnetic energy as it expands.

Corrective Maneuvers Used in Different Scoliosis Deformities With the Experience of 72 Operated Patients.

PURPOSE: This study aimed to show the correction maneuvers used in scoliosis surgery and give hints and tips on achieving optimal correction with the help of visual content. MATERIALS AND METHODS: Seventy-two scoliosis patients with 96 major curves operated between 2011 and 2018 evaluated retrospectively. Seven different correction maneuvers (Ucar convex rod rotation technique, cantilever technique, convex double-rod rotation technique, convex double-rod translation technique, double-rod rotation with coronal bending, convex rod rotation with coronal bending, direct vertebral rotation) were used in these surgeries alone or together. Each method is explained with figures and videos. Type of scoliosis, follow-up time, age, preoperative and postoperative degree of curvature, amount of correction, surgical time, amount of transfusion, hemoglobin level, and hospital stay were evaluated. RESULTS: The mean follow-up was 42.5 (24-108) months, and the mean age was 15.8 (12-29) years. The mean preoperative scoliosis angle of the patients was 75.9 (50-139) degrees, and the final follow-up was 15.6 (5-40) degrees. The scoliotic deformity correction rate was 79.3%. The mean preoperative thoracic kyphosis of the patients was 58.7 (12-110) degrees, and the final follow-up was 41.2 (25-62) degrees. The mean surgical time was 293 (160-440) minutes. The mean hospitalization length was 5.8 (2-21) days. The blood delivered to patients during surgery and postoperative was 715 (300-1800) mL. There was a statistically significant difference between the preoperative and final follow-up scoliosis angle ( P =0.000). CONCLUSIONS: Providing an ideal correction without damaging the spinal cord depends on correctly applying the correction maneuvers. The use of correction maneuvers alone or in combination in the appropriate order will shorten the duration of the case, decrease the amount of bleeding, shorten the hospital stay, increase the amount of correction, and reduce complications.

Small vessel disease is associated with later onset of major adverse cardiovascular events after acute cervicocerebral artery dissection.

BACKGROUND: Cerebral small vessel disease (CSVD) is common among the elderly and has been associated with an increased risk of major adverse cardiac events (MACE) and increased risk of long-term disability. Little is known whether CSVD affects outcomes after cervicocerebral artery dissection (CAD), which predominantly affects younger patients. Specifically, there is a paucity as to whether CSVD increases the risk of MACE after CAD and whether this risk is different for early versus late events. METHODS: We retrospectively analyzed 140 consecutive patients with acute CAD. We determined CSVD on MRI using the STRIVE criteria and calculated the CSVD sum score based on the individual CSVD components. For statistical analysis the CSVD burden was dichotomized to mild (score 0-1) versus severe (score 2-4). The primary outcome of interest was the 6-month MACE risk. Secondary outcomes of interest were early versus late MACE, stroke at presentation, and good 90-day outcome (modified Rankin Scale score 0-2). RESULTS: There was no difference in overall MACE between subjects when stratified by CSVD burden (10.1% versus 9.8%, Log-rank P = 0.953). We found that patients with severe CSVD had significantly more late MACE as compared to mild CSVD (9.8% versus 1.1%, P = 0.024). There was no significant difference in the prevalence of stroke at the time of CAD diagnosis (50.6% versus 47.1%, P = 0.690) and the 90-day disability-free survival in subjects with mild versus severe CSVD (93.7% versus 91.7%, P = 0.729). CONCLUSION: Severe CSVD burden was associated with a significantly greater risk of late MACE. CSVD assessment in CAD patients may aid risk stratification and treatment optimization.

Placental T-Cadherin Correlates With Trophoblastic Invasion Anomalies: Placenta Percreta and Fetal Growth Restriction.

In this study, we compared the placental T-cadherin staining intensity of pregnant women with placenta percreta (PP) and asymmetrical fetal growth restriction (FGR) compared with healthy control pregnancies. Placental T-cadherin levels of the placenta of 86 pregnant women in total, 25 with FGR, 30 with healthy pregnant subjects, and 31 with PP, were examined using monoclonal anti-T-cadherin (CDH13) antibody for immunohistochemical examination. In immunohistochemistry, H -scores were used for each group to compare the expression of T-cadherin in extravillous trophoblast (EVT) cells. T-cadherin H -score of EVTs was highest in the FGR group and the lowest in the PP group. The difference in H -score between the FGR group and the control group was not statistically significant ( P =0.344). The difference between the PP group and the other 2 groups was significant ( P <0.0001). Multivariable linear regression analysis with a stepwise elimination method was performed in order to identify demographic and clinical parameters with significant effects on the T-cadherin H -score of EVTs. The estimation results identified only the disease group as a significant predictor of the H -score of EVTs ( R2 =0.340, P <0.0001). The highest T-cadherin H -score of EVTs was found in the FGR group and the lowest in the PP group. The low T-cadherin H-score values in the PP group suggest that low T-cadherin EVTs may be associated with increased placental invasion. Likewise, despite the statistical insignificance, a higher T-cadherin H -score of EVTs in FGR compared with controls implies a decreased invasiveness of the placenta in FGR.

Comparison of Two Clinical Chemistry Analyzers by Total Analytical Error and Measurement Uncertainty.

BACKGROUND: Although analytical errors contain a small portion of laboratory errors, they are important in terms of intervention ability and practicality of follow-up by laboratory professionals. Also, from this point of view, the test results' quality, reliability, and accuracy are crucial to laboratories. Therefore, to determine analytical performance parameters for quality management in the analytical phase, clinical laboratories utilize total analytical error (TAE), bias, coefficient of variation (CV), and uncertainty of measurement (MU). METHODS: Fifteen biochemistry parameters were compared with Beckman Coulter AU 5800 for 2017 - 2018 and Roche Cobas 8000 for 2019 - 2020 in terms of TAE and MU. The results were evaluated between devices and compared with the EuBIVAS, CLIA, RCPA, PRDEQA%, pUQEAS%, pU%, and TEa-TR datasets. RESULTS: There were no significant differences between the devices for the mentioned periods. Device performances resulted in similar outcomes. During our four-year study, nearly all of our tests failed for EuBIVAS, RCPA, and pU%. On the contrary, almost all of our parameters gave valid results according to the CLIA, PRDEQA%, pUQEAS%, and TEa-TR ranges. CONCLUSIONS: It is crucial to distinguish between "mistake" and "uncertainty." The discrepancy between the measured value and the 'actual value' is called error. Uncertainty is a measure of how confident you are in the measurement outcome. We endeavor to remedy any known inaccuracies wherever feasible by applying adjustments from calibration certifications. On the other hand, any inaccuracy whose value is unknown is a cause of doubt.

Detangling the Structural Neural Correlates Associated with Resting versus Dynamic Phantom Limb Pain Intensity Using a Voxel-based Morphometry Analysis.

The management of phantom limb pain (PLP) is still challenging due to a partial understanding of its neurophysiological mechanisms. Structural neuroimaging features are potential biomarkers. However, only a few studies assessed their correlations with clinical severity and treatment response. This study aims to explore the association between brain gray matter volume (GMV) with phantom limb manifestations severity and PLP improvement after neuromodulatory treatments (transcranial direct current stimulation and mirror therapy). Voxel-based morphometry analyses and functional decoding using a reverse inference term-based meta-analytic approach were used. We included 24 lower limb traumatic amputees with moderate to severe PLP. We found that alterations of cortical GMV were correlated with PLP severity but not with other clinical manifestations. Less PLP severity was associated with larger brain clusters GMV in the non-affected prefrontal, insula (non-affected mid-anterior region), and bilateral thalamus. However, only the insula cluster survived adjustments. Moreover, the reverse inference meta-analytic approach revealed that the found insula cluster is highly functionally connected to the contralateral insula and premotor cortices, and the decoded psychological processes related to this cluster were "rating," "sustained attention," "impulsivity, " and "suffering." Moreover, we found that responders to neuromodulatory treatment have higher GMV in somatosensory areas (total volume of S1 and S2) in the affected hemisphere at baseline, compared to non-responders, even after adjustments.

Cost-Effectiveness Analysis to Inform Randomized Controlled Trial Design in Chronic Pain Research: Methods for Guiding Decisions on the Addition of a Run-In Period.

Introduction: Run-In (RI) periods can be used to improve the validity of randomized controlled trials (RCTs), but their utility in Chronic Pain (CP) RCTs is debated. Cost-effectiveness analysis (CEA) methods are commonly used in evaluating the results of RCTs, but they are seldom used for designing RCTs. We present a step-by-step overview to objectively design RCTs via CEA methods and specifically determine the cost effectiveness of a RI period in a CP RCT. Methods: We applied the CEA methodology to data obtained from several noninvasive brain stimulation CP RCTs, specifically focusing on (1) defining the CEA research question, (2) identifying RCT phases and cost ingredients, (3) discounting, (4) modeling the stochastic nature of the RCT, and (5) performing sensitivity analyses. We assessed the average cost-effectiveness ratios and incremental cost effectiveness ratios of varied RCT designs and the impact on cost-effectiveness by the inclusion of a RI period vs. No-Run-In (NRI) period. Results: We demonstrated the potential impact of varying the number of institutions, number of patients that could be accommodated per institution, cost and effectiveness discounts, RCT component costs, and patient adherence characteristics on varied RI and NRI RCT designs. In the specific CP RCT designs that we analyzed, we demonstrated that lower patient adherence, lower baseline assessment costs, and higher treatment costs all necessitated the inclusion of an RI period to be cost-effective compared to NRI RCT designs. Conclusions: Clinical trialists can optimize CP RCT study designs and make informed decisions regarding RI period inclusion/exclusion via CEA methods.

C-reactive protein-to-lymphocyte ratio is a reliable marker in patients with COVID-19 infection: the CLEAR COVID study.

OBJECTIVE: COVID-19 infection is characterized with elevation of inflammatory markers in bloodstream. A novel inflammatory marker, C-reactive protein (CRP)-to-lymphocyte ratio (CLR), is suggested to be associated with inflammation. We aimed to compare the CLR values of the deceased COVID-19 patients to the CLR of survived subjects. MATERIALS AND METHODS: The patients with COVID-19 whom presented to outpatient or inpatient clinics of AbantIzzet Baysal University Hospital were enrolled to the present retrospective study. Subjects were grouped as either deceased or survived. CLR values of the groups were compared. RESULTS: Study cohort was consisted of 568 subjects in deceased and 4753 patients in survived group. Median CLR of the deceased and survived groups were 90 (0.2-1679)% and 11 (0.2-1062)%, respectively (p < 0.001). The sensitivity (75%) and specificity (70%) of CLR (> 23.4% level) in detecting mortality were higher than those of CRP and ferritin (AUC 0.80, p < 0.001, 95% CI 0.78-0.82). CONCLUSION: We suggest that elevated CLR levels in COVID-19 patients on admission should alert physicians for poor outcome.

OBJETIVO: La infección por Covid-19 se caracteriza por elevación de marcadores inflamatorios en el torrente sanguíneo. Se sugiere que un nuevo marcador inflamatorio, la proporción de C-reactive protein (CRP) a linfocitos (CLR), está asociado con la inflamación. Nuestro objetivo fue comparar los valores de CLR de los pacientes fallecidos con Covid-19 con el CLR de los sujetos sobrevivientes. MATERIALES Y MÉTODOS: Los pacientes con Covid-19 que se presentaron en clínicas ambulatorias o de hospitalización del Hospital Universitario Abant Izzet Baysal se inscribieron en el presente estudio retrospectivo. Los sujetos se agruparon como fallecidos o sobrevivientes. Se compararon los valores de CLR de los grupos. RESULTADOS: La cohorte del estudio estuvo compuesta por 568 sujetos en el grupo fallecido y 4753 pacientes en el grupo sobreviviente. La mediana de CLR de los grupos fallecidos y sobrevivientes fue 90 (0.2-1679)% y 11 (0.2-1062)%, respectivamente (p < 0.001). La sensibilidad (75%) y la especificidad (70%) de CLR (nivel > 23.4%) en la detección de mortalidad fueron superiores a las de CRP y ferritina (AUC 0.80, p < 0.001, IC 95%: 0,78-0.82). CONCLUSIÓN: Sugerimos que los niveles elevados de CLR en pacientes con Covid-19 al ingreso deberían alertar a los médicos sobre un resultado deficiente.

Acousto-holographic reconstruction of whole-cell stiffness maps.

Accurate assessment of cell stiffness distribution is essential due to the critical role of cell mechanobiology in regulation of vital cellular processes like proliferation, adhesion, migration, and motility. Stiffness provides critical information in understanding onset and progress of various diseases, including metastasis and differentiation of cancer. Atomic force microscopy and optical trapping set the gold standard in stiffness measurements. However, their widespread use has been hampered with long processing times, unreliable contact point determination, physical damage to cells, and unsuitability for multiple cell analysis. Here, we demonstrate a simple, fast, label-free, and high-resolution technique using acoustic stimulation and holographic imaging to reconstruct stiffness maps of single cells. We used this acousto-holographic method to determine stiffness maps of HCT116 and CTC-mimicking HCT116 cells and differentiate between them. Our system would enable widespread use of whole-cell stiffness measurements in clinical and research settings for cancer studies, disease modeling, drug testing, and diagnostics.

C-Reactive Protein to Albumin Ratio in Patients with Prediabetes and Diabetes Mellitus: HbA1c and Inflammation.

BACKGROUND: Inflammation has a significant status in both the pathogenesis and complications of diabetes mellitus (DM). The aim of this study is to compare the C-reactive protein (CRP) to albumin ratio (CAR) values in controlled DM, uncontrolled DM, prediabetes groups grouped by HbA1c as well as in a group of healthy individuals. METHODS: In this retrospective study, 6,993 DM patients, 770 prediabetes patients, and 1,340 healthy individuals were included. According to their HbA1c levels, DM patients were divided into two groups as controlled DM (HbAlc < 6.5%, n = 4,115) and uncontrolled DM (HbAlc ≥ 6.5%, n = 2,878). RESULTS: The CRP and CAR levels were significantly higher in the DM and prediabetes group than in the control group (p < 0.05, for both). Albumin levels were significantly lower in the DM group than in both the prediabetes and control groups (p < 0.05, for both). In the uncontrolled DM group, CRP and CAR values were found to be significantly higher than the control and controlled DM groups, while albumin values were significantly lower than the control group, prediabetes group, and controlled DM group (p < 0.05, for all). CONCLUSIONS: It is thought that CAR, a liver related inflammatory marker, can be applied as an inflammation marker in both prediabetes, determined by HbA1c, and patients diagnosed with DM. Further prospective studies will better demonstrate the utility of CAR values as an inflammatory marker in DM and prediabetes.

Technoeconomic Evaluation of the Industrial Implementation of Catalytic Direct Nonoxidative Methane Coupling.

This paper presents a process design for catalytic nonoxidative natural gas conversion to olefins and aromatics, highlighting the opportunities and challenges concerning industrial implementation. The optimal reactor conditions are 5 bar and 1000 °C. Heat exchange over the reactor is challenging due to the high temperature and low gas pressure. Recovery of ethylene is economically unattractive due to the low ethylene concentration in the product stream, leading to a methane-to-aromatics process, recycling ethylene. Benzene is the most valuable product at an efficiency of 0.31 kgbenzene/kgmethane with hydrogen as a major valuable byproduct. Naphthalene, with a low value, is unfortunately the dominant product, at 0.52 kgnaphthalene/kgmethane. It is suggested to hydrocrack the naphthalene to more valuable BTX products in an additional downstream process. The process is calculated to result in a 107 $ profit per ton CH4.

A Novel Multimodal Treatment Method and Pilot Feasibility Study for Vaginismus: Initial Experience With the Combination of Sacral Erector Spinae Plane Block and Progressive Dilatation.

Background Genito-pelvic pain/penetration disorder, commonly referred to as vaginismus, is a relatively common condition in women of childbearing age and has physical and psychological aspects. Various cognitive and behavioral therapies, dilatators, botulinum injections, and so on have been tried in the treatment. We hypothesize that the combination of sacral erector spinae plane (ESP) block and progressive dilatation treatment increases treatment quality. Methods We performed the sacral ESP block and progressive dilatation, which we added to multimodal treatment for resistant vaginismus cases. After the procedure, all patients were followed up during one menstrual cycle. They were recommended to have sexual intercourse on the day of the procedure. Results In 15 of our treatment-resistant cases, when we added the sacral ESP block, successful penetration after the first block was 73%. Pregnancy occurred in eight patients after the initial one-month follow-up. Four of the 15 patients needed a second block. Conclusions The sacral ESP block added to the multimodal treatment protocol significantly improves treatment quality.

Stellate ganglion ischemia on the prevention of pulmonary vasospasm during bilateral carotid artery ligation: The first experimental study.

Fatal pulmonary edema and hemorrhage are significant complications of endovascular treatment in steno-occlusive carotid artery disease; a rational mechanism has not been adequately examined in the literature so far. We investigated if cervical sympathetic ganglia ischemia prevents pulmonary vasospasm on the prognosis of bilateral common carotid artery ligation (BCCAL). Twenty-three adult New Zealand rabbits (4.2 ± 0.3 kg) were randomly divided into three groups: the control group (G1, n = 5), the sham group (G2, n = 6), and the BCCAL group (G3, n = 12). Common carotid arteries were dissected bilaterally in G2/G3, and permanent BCCAL was applied to only in G3. All animals were followed for 3 weeks and decapitated under general anesthesia. Histopathological changes in stellate ganglia and severity of pulmonary vasospasm-related lung edema and hemorrhage were investigated. Results were analyzed by the Kruskal-Wallis test. Two animals of G3 dead within three weeks and the remainder were sacrificed three weeks later. Subpleural petechial foci and an endotracheal bloody fluid collection were grossly observed in the lungs. Histopathologically, pulmonary artery vasospasm, perivascular and subintimal edema, interalveolar hemorrhage, and alveolar wall destructions were observed with less ischemic-degenerated neuron density-determined stellate ganglia animals. Neurodegeneration of stellate ganglia may have a beneficial effect on the prevention of lung injury during steno-occlusive carotid artery disease.

Subarachnoid block and ultrasound-guided transversalis fascia plane block for caesarean section: A randomised, double-blind, placebo-controlled trial.

BACKGROUND: After caesarean section, maternal postoperative comfort is critical to allow the new mother to care for her baby. Insufficient pain relief during the postoperative period may delay maternal/infant bonding and, in addition, such pain has been linked to subsequent depression and chronic pain. Caesarean section is commonly performed with a Pfannenstiel incision, and a transversalis fascia plane (TFP) block provides postoperative analgesia in the T12 and L1 dermatomes. OBJECTIVE: The aim of this study was to investigate the effect of the TFP block on postoperative opioid consumption and pain scores in patients undergoing caesarean section under spinal anaesthesia. DESIGN: A randomised controlled, double-blind study. SETTINGS: Single-centre, academic hospital. PARTICIPANTS: Sixty patients undergoing caesarean section. INTERVENTIONS: The TFP group (n = 30) received an ultrasound-guided bilateral TFP block with 20 ml of 0.25% bupivacaine. The control group (n = 30) received 20 ml of saline bilaterally. Postoperative analgesia was given every 6 h with intravenous paracetamol 1 g and patient-controlled analgesia (PCA) with morphine. MAIN OUTCOME MEASURES: Postoperative visual analogue pain scores, morphine consumption, rescue analgesia and opioid-related side effects were evaluated. RESULTS: In the TFP group, the visual analogue pain scores were significantly lower at rest for 2 h after the operation (P = 0.011) and during active movement at 2, 4 and 8 h postoperatively (P = 0.014, <0.001 and 0.032, respectively). Morphine consumption in the first 24 h after surgery was significantly higher in the control group compared with the TFP group (38.5 ±â€Š11.63 and 19.5 ±â€Š8.33 mg, respectively; P < 0.001). The incidence of postoperative nausea and constipation were statistically higher in the control group than in the TFP group (P < 0.05). Patient satisfaction was significantly higher in the TFP group (P = 0.027). CONCLUSION: A postoperative TFP block can reduce opioid consumption and relieve acute pain after a caesarean section under spinal anaesthesia. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04172727.

Does the Serratus Plane Block Added to the Interscalene Block Improve the Quality of Anesthesia in Arthroscopic Shoulder Surgery? A Prospective Randomized Study.

BACKGROUND: Interscalene brachial plexus block (ISBPB) is the gold standard method in shoulder surgery. Serratus plane block (SPB) provides anesthesia in hemithorax, axillary region, and posterior of the shoulder. This randomized controlled study evaluated the effect of SPB added to ISBPB on surgical anesthesia quality in arthroscopic shoulder surgery. METHODS: Sixty patients undergoing arthroscopic shoulder surgery were randomly assigned to two groups. All surgeries were performed under regional anesthesia. The Group I (Group Interscalene) (n=30) received ultrasound-guided interscalene block. In the Group IS (Group Interscalene + Serratus) (n=30), ultrasound-guided interscalene block and SPB were performed. Intraoperative anesthetic agent consumption, postoperative opioid consumption, postoperative pain scores, patient satisfaction, and surgeon satisfaction were evaluated. RESULTS: Intraoperative propofol (60.00 ± 45.49 vs. 24.00 ± 32.97, respectively) and fentanyl (33.33 ± 23.97 vs. 18.33 ± 24.51, respectively) consumption were significantly higher in Group I than in Group IS (p < 0.05). There was no statistically significant difference between the groups at any of the times the postoperative opioid consumption and pain scores were evaluated (p > 0.05). CONCLUSIONS: SPB added to the ISBPB increases the quality of surgical anesthesia and reduces the need for intraoperative sedoanalgesia for arthroscopic shoulder surgery.

Gallic and carnosic acids improve quality of frozen-thawed ram spermatozoa.

The objective was to determine effects of gallic acid (GA) and carnosic acid (CA), present in carob pods and rosemary extract respectively, on frozen-thawed ram spermatozoa. Thirty ejaculates were collected from five Merino rams, pooled, diluted in Tris-based extender and divided into five equal portions containing: 0.05 or 2 mM of GA; 0.05 or 0.2 mM of CA; or no additive (control). Extended semen was equilibrated at +4°C, loaded into straws, held 5 cm above liquid nitrogen for 12 min then plunged. Computer-aided sperm analysis was used to assess motility, whereas flow cytometry was used to assess high mitochondrial membrane potential (HMMP) and percentages of spermatozoa with plasma membrane and acrosome integrity (PMAI). Spermatozoa supplemented with 2 mM GA had greater total motility than control spermatozoa (39.9 ± 3.01 vs. 29.2 ± 1.31%, mean ± SEM, p < .05). The PMAI was greatest in 0.2 mM CA (13.3 ± 0.68%), whereas HMMP was highest in 0.05 mM CA but lowest in control (22.9 ± 4.95 and 11.4 ± 3.64% respectively; p < .05). In conclusion, for cryopreservation of ram semen in Tris-based extender, supplementation with 2 mM GA increased post-thaw motility, whereas supplementation with 0.05 mM CA enhanced mitochondrial function.

Preventive effect of intravesical ozone supplementation on n-methyl-n-nitrosourea-induced non-muscle invasive bladder cancer in male rats.

Although non-muscle invasive bladder cancer (NMIBC) is widely seen in men, most laboratory studies of new intravesical therapies to prevent NMIBC have been conducted on female animals. In addition, ozone (O3) has been shown to be a beneficial agent as an intravesical application in the treatment of various disorders. In the current study, we evaluated the immunohistopathological and oxidative-antioxidative effects of intravesical O3 treatment on n-methyl-n-nitrosourea (MNU)-induced NMIBC. Male Wistar-Albino rats (n=51) were divided into four groups: sham (n=6), O3 only (n=15), MNU only (n=15), and MNU+O3 (n=15). The MNU-only and MNU+O3 groups received MNU, and the O3-only group received saline every other week for 10 weeks. The MNU-only group received 1 ml saline in place of O3 treatment, whereas the O3-only and MNU+O3 groups were treated with 1 ml 25 µg/ml O3 between the 7th and 12th weeks. Rat bladders were collected in the 15th week for immunohistopathology and oxidant-antioxidant quantitation. Oxidant-antioxidant parameters were determined by ELISA. Although all surviving rats in the MNU-only group had preneoplastic (4/11, 36.4%) or neoplastic changes (7/11, 63.6%), a completely normal urothelium was observed in 2 rats (2/12, 16.7%) in the MNU+O3-group (P=0.478). More high-grade lesions were observed in the MNU-only group (4/11, 36.4%) than in the MNU+O3 group (1/12, 8.3%) (P=0.120). All oxidant-antioxidant parameters significantly increased (P<0.05) in the O3-only group compared with the sham group. However, only antioxidant superoxide dismutase was remarkably higher (178.9%, P=0.060) in the MNU+O3 group compared with the MNU-only group. This is the first methodologically and pathologically well-described male rat orthotopic bladder carcinogenesis model with intravesical MNU and administration of O3 in NMIBC.

Molecular Scale Description of Anion Competition on Amine-Functionalized Surfaces.

Many industrial and biological processes involve the competitive adsorption of ions with different valencies and sizes at charged surfaces; heavy and precious metal ions are separated on the basis of their propensity to adsorb onto interfaces, often as anionic ion clusters (e.g., [MClx]n-). However, very little is known, both theoretically and experimentally, about the competition of factors that drive preferential adsorption, such as charge density or valence, at interfaces in technologically relevant systems. There are even contradictory pictures described by interfacial studies and real life applications, such as chlorometalate extractions, in which charge diffuse chlorometalate ions are extracted efficiently even though charge dense chloride ions present in the background are expected to occupy the interface. We studied the competition between divalent chlorometalate anions (PtCl62- and PdCl42-) and monovalent chloride anions on positively charged amine-functionalized surfaces using in situ specular X-ray reflectivity. Chloride anions were present in vast excess to simulate the conditions used in the commercial separation of heavy and precious metal ions. Our results suggest that divalent chlorometalate adsorption is a two-step process and that the divalent anions preferentially adsorb at the interface despite having a charge/volume ratio lower than that of chloride. These results provide fundamental insight into the structural mechanisms that underpin transport in phases that are relevant to heavy and precious metal ion separations, explaining the high efficiency of low charge density ion transport processes in the presence of charge dense anions.

Cerebral aspergillosis and pulmonary tuberculosis in a child with chronic granulomatous disease.

BACKGROUND: Chronic granulomatous disease (CGD) is an immune disorder that affects phagocytes. It is characterized by recurrent or persistent bacterial and fungal infections. Reports of tuberculosis (TB) in patients with CGD are rare. In developing countries, where TB is endemic, possibility of other chronic infections is often overlooked by physicians. CASE DESCRIPTION: We report the case of a 4-year-old boy who had recurrent respiratory infections and episodes of headache. He was put on antituberculosis (ATT) drugs without microbiological or pathological evidence 2 months prior to presentation. The child did not improve and was brought to our hospital where a computed tomography scan revealed multiple cerebral abscesses. These abscesses were excised. The microbiological specimen was determined to be positive for Aspergillus fumigatus. His tracheal aspirate was positive for Mycobacterium tuberculosis polymerase chain reaction assay. Further work-up confirmed the diagnosis of CGD in the child. CONCLUSION: This report describes the course of the patient's illness in order to highlight the challenges associated with the management of these infections. We also aim to stress on the importance of pathological diagnosis before starting a therapy.