Notes

From Facts to be able to Medical Recommendations within Antibiotic Therapy in Severe Otitis Mass media in kids.
Triple-negative breast cancer (TNBC) is one of the most aggressive subtypes of breast cancer and the major phenotype of BRCA related hereditary breast cancer. Platinum is a promising chemotherapeutic agent for TNBC. However, its efficacy for breast cancer with BRCA germline mutation remains inconclusive. Here we present a meta-analysis to evaluate the effect of platinum agents for breast cancer patients with BRCA mutation in neoadjuvant setting.

Pubmed, Embase, and Cochrane Central Register of Controlled Trials databases were searched for relevant studies on neoadjuvant platinum treatment and BRCA related breast cancer. Fixed- and random-effect models were adopted for meta-analyses. Heterogeneity investigation was conducted by sensitivity and subgroup analyses. Publication bias was evaluated by funnel plot and Begg's test.

In all, five studies with 363 patients were included for meta-analysis. The pooled pathological complete response (pCR) rates were 43.4% (59/136) and 33.9% (77/227) for platinum and ctic value of platinum for breast cancer neoadjuvant treatment.Acute promyelocytic leukemia (APL) has become a highly curable disease after four decades of endeavors. Thanks to the efforts of investigators throughout the world, the chemo-free concept has become a reality for both low- and high-risk patients. All-trans retinoic acid (ATRA) plus arsenic trioxide (ATO) without chemotherapy has become a first-line treatment for newly diagnosed APL and has been adopted in guidelines or expert recommendations from the NCCN and ELN and in China. Though the regimen has achieved great success, challenges still exist. The rate of early death still has not diminished significantly and is a major obstacle to curing all patients. Leukocytosis is the most important factor for ED, and completely abandoning chemotherapy is dangerous for certain patients in practice. To narrow the gap between guidelines and practice, this review aims to examine the history of the chemo-free model for the treatment of APL in the arsenic-alone era (1974-2002) and the arsenic plus ATRA era (2002-present) and provide practical considerations regarding early death.
The positivity of sentinel lymph node (SLN) metastasis is relatively low in ductal carcinoma
(DCIS) patients. The aim of this study was to investigate factors associated with SLN metastasis and build a model to predict the potential risk of SLN metastasis in patients with a preoperative diagnosis of DCIS.

Core needle biopsy-proved DCIS patients who underwent SLN biopsy and breast surgery were retrospectively reviewed and selected. Univariate analysis was used to identify the variables correlated with SLN metastasis. A model to predict SLN metastasis was developed using a multivariate logistic regression in the training set and then validated in an internal set.

A total of 407 patients with a preoperative diagnosis of DCIS were included. Upstaging to invasive/microinvasive cancer occurred in 225 patients after surgery. SLN metastasis was found in 42 patients, including 32 patients upstaging to invasive disease, 8 to microinvasive disease, and 2 pure DCIS. Tumor size based on US examination, axillary ultrasound finding, multifocality, surgery, upstaging, and Ki-67 expression were significantly related to SLN metastasis. The model incorporating tumor size, axillary ultrasound finding and multifocality yielded an AUC of 0.805 (95% CI 0.715-0.895,
<0.001) in the training set, and 0.729 (95% CI 0.547-0.911,
=0.013) in the testing set.

A simple model was developed to predict SLN metastasis in patients with a preoperative diagnosis of DCIS. With good discriminatory power, this model should be helpful for surgeons to decide if SLN biopsy could be safely avoided in certain patients.
A simple model was developed to predict SLN metastasis in patients with a preoperative diagnosis of DCIS. With good discriminatory power, this model should be helpful for surgeons to decide if SLN biopsy could be safely avoided in certain patients.
Adding bevacizumab, an anti-Vascular Endothelial Growth Factor (VEGF), to platinum-based chemotherapy/pemetrexed in 1
line treatment of advanced malignant pleural mesothelioma (MPM), significantly improved overall survival. However, increased high grade bleeding after operation was reported in patients with colorectal cancer who previously received bevacizumab. In the present analysis, we assessed for the first time the impact of adding bevacizumab to induction chemotherapy prior to surgery for mesothelioma patients.

Two hundred twenty-seven MPM patients, intended to be treated with induction chemotherapy followed by surgery at the University Hospital of Zurich between 2002 and December 2018, were included in the present analysis. After propensity score matching for gender, histology and age (13 ratio), data from 88 patients were analyzed. Sixty-six patients underwent induction chemotherapy (with cis-/carboplatin and pemetrexed control group) alone and 22 patients underwent induction chemotherapy with ton chemotherapy with bevacizumab without increased intra- and postoperative bleeding complications. Response rates were significantly improved by the addition of bevacizumab.
Current reports on the prognostic and predictive value of hypoxia-inducible factor-1α (HIF-1α) in endometrial carcinoma are inconsistent. Therefore, we conducted this meta-analysis to precisely evaluate the association of HIF-1α expression with susceptibility, clinical features, and prognosis of endometrial cancer.

Eligible studies that assessed the role of HIF-1α protein expression, immunohistochemistry detection, disease susceptibility, clinical features, and prognosis of endometrial cancer were searched from the Embase, Pubmed, and Web of Science databases. Stata 14.0 software was used to merge and compute pooled hazard ratios (HR) and odds ratios (OR). Information including HIF-1α protein expression and clinical progression of endometrial cancer was extracted. The pooled HR and OR with corresponding 95% confidence intervals (CI) were used to estimate the strength of these associations.

A total of 25 studies were included in the analysis. HIF-1α protein expression in endometrial cancer tissue was significantly higher than that in normal tissues (OR = 15.79, 95% CI = 8.44-29.52,
< 0.05). Endometrial cancer patients with higher HIF-1α protein expression had poorer prognosis compared to patients with low HIF-1α protein expression (HR = 2.29, 95% CI = 1.68-2.90,
< 0.05). In addition, high HIF-1α protein expression was significantly associated with endometrial cancer grade, lymph node metastasis, and myometrial invasion (grade in Caucasians OR = 3.09, 95% CI = 1.63-5.85,
< 0.05; lymph node metastasis OR = 3.09, 95% CI = 1.63-5.85,
< 0.05; myometrial invasion OR = 2.26, 95% CI = 2.15-5.08,
< 0.05).

HIF-1α overexpression was significantly associated with increased risk, advanced clinical progression, and poor prognosis in endometrial cancer patients.
HIF-1α overexpression was significantly associated with increased risk, advanced clinical progression, and poor prognosis in endometrial cancer patients.
The diagnosis of malignant pleural mesothelioma (MPM) can be difficult, in part due to the difficulty in distinguishing between MPM and reactive mesothelial hyperplasia (RMH). The tumor suppressor gene, CDKN2A, is frequently silenced by epigenetic mechanisms in many cancers; in the case of MPM it is mostly silenced
genomic deletion. Co-deletion of the CDKN2A and methylthioadenosine phosphorylase (MTAP) genes has been researched extensively and discovered to be a highly specific characteristic of MPM. Most studies have used FISH to detect the deletion of CDKN2A and IHC for MTAP as a surrogate for this. In this study, we aim to investigate and validate droplet digital PCR (ddPCR) as an emerging alternative and efficient testing method in diagnosing MPM, by particularly emphasizing on the loss of MTAP and CDKN2A.

This study included 75 formalin fixed paraffin embedded (FFPE) MPM tissue, and 12 normal pleural tissue and 10 RMH as control. Additionally, primary MPM cell lines and normal pleural samples werey concordant with FISH that is currently used in diagnosing MPM. ddPCR detection of these genetic losses can potentially be utilized as an alternative method in the diagnosis of MPM and for the future development of a less-invasive MPM-specific detection technique on MPM tumor tissue DNA.
Our study confirms that MTAP is often co-deleted with CDKN2A in MPM. Our in-house designed ddPCR assays for MTAP and CDKN2A are useful in differentiating MPM from RMH, and is highly concordant with FISH that is currently used in diagnosing MPM. ddPCR detection of these genetic losses can potentially be utilized as an alternative method in the diagnosis of MPM and for the future development of a less-invasive MPM-specific detection technique on MPM tumor tissue DNA.Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive malignant tumors and there is a lack of biomarkers for ESCC diagnosis and prognosis. Family subunits of cholinergic nicotinic receptor genes (CHRNs) are involved in smoking behavior and tumor cell proliferation. Previous researches have shown similar molecular features and pathogenic mechanisms among ESCC, head and neck squamous cell carcinoma (HNSC), and lung squamous cell carcinoma (LUSC). Using edgeR, three mutual differentially expressed genes of CHRNs were found to be significantly upregulated at the mRNA level in ESCC, LUSC, and HNSC compared to matched normal tissues. Kaplan-Meier survival analysis showed that high expression of CHRNB4 was associated with unfavorable prognosis in ESCC and HNSC. The specific expression analysis revealed that CHRNB4 is highly expressed selectively in squamous cell carcinomas compared to adenocarcinoma. Cox proportional hazards regression analysis was performed to find that just the single gene CHRNB4d in SCCs, and may serve as a promising biomarker for diagnosis and prognosis prediction, and it can even become a therapeutic target of ESCC patients.Two-dimensional layered nanomaterial Ti3C2TX (a member of the MXene family) was used to immobilise enzyme sarcosine oxidase to fabricate a nanostructured biosensor. The device was applied for detection of sarcosine, a potential prostate cancer biomarker, in urine for the first time. The morphology and structures of MXene have been characterised by atomic force microscopy (AFM) and scanning electron microscopy (SEM). Electrochemical measurements, SEM and AFM analysis revealed that MXene interfaced with chitosan is an excellent support for enzyme immobilisation to fabricate a sensitive biosensor exhibiting a low detection limit of 18 nM and a linear range up to 7.8 µM. The proposed biosensing method also provides a short response time of 2 s and high recovery index of 102.6% for detection of sarcosine spiked into urine sample in a clinically relevant range.There is an upsurge enthusiasm for utilizing biochar produced from waste-biomass in different fields, to address the most important ecological issues. This review is focused on an overview of remediating harmful contaminants utilizing biochar. Production of biochar utilizing various systems has been discussed. Biochar has received the consideration of numerous analysts in building up their proficiency to remediate contaminants. Process parameters are fundamentally answerable for deciding the yield of biomass. Biochar derived from biomass is an exceptionally rich wellspring of carbon produced from biomass utilizing thermal combustion. Activating biochar is another particular region for the growing utilization of biochar for expelling specific contaminations. Closed-loop systems to produce biochar creates more opportunities. Decentralized biochar production techniques serve as an effective way of providing employment opportunities, managing wastes, increasing resource proficiency in circular bioeconomy. This paper also covers knowledge gaps and perspectives in the field of remediation of toxic pollutants using biochar.The safety and bioactive potential of crude carotenoid extract from Cantaloupe melon nanoencapsulated in porcine gelatin (EPG) were evaluated in a chronic inflammatory experimental model. Animals were fed a high glycemic index and high glycemic load (HGLI) diet for 17 weeks and treated for ten days with 1) HGLI diet, 2) standard diet, 3) HGLI diet + crude carotenoid extract (CE) (12.5 mg/kg), and 4) HGLI diet + EPG (50 mg/kg). General toxicity signals were investigated, considering body weight, food intake, hematological, biochemical parameters, relative weight, morphology, and histopathology of organs. The biochemical parameters indicated the low toxicity of EPG. Acute hepatitis was observed in animals' livers, but CE and EPG groups presented improved tissue appearance. Chronic enteritis was observed in animals, with villi and intestinal glands preservation in the EPG group. The results suggest the safety and the bioactive effect of EPG, possibly related to its anti-inflammatory potential.Urinary tract infections (UTIs) are induced by exogenous organisms including extraintestinal pathogenic such as Escherichia coli (ExPEC), Proteus mirabilis and Klebsiella pneumonia, which are closely related. These organisms can colonize in the urinary tract and cause UTIs. In this study, a cross-reactive multi-epitope vaccine was designed by two constructs to stimulate the immune system (CD8+ and CD4 + T cells) against ExPEC, Proteus mirabilis and Klebsiella pneumonia strains. Uropathogenic Escherichia coli (UPEC), Proteus mirabilis and Klebsiella pneumoniae are the main bacterial cause of UTI. They were used for designing experimental candidate vaccine, and their immunogenicity and protectivity were assessed. In this study, conserved antigens from their bacterial genomes were considered, and informatics-based immunological vaccine with cross-protective T and B-cells epitopes was designed and evaluated. The vaccine candidate was used as a broad immune system inducer, and its cross-protective immunity and protectivity were confirmed in in vivo experiments.Anoxygenic phototrophic bacteria (APB) are a phylogenetically diverse group of organisms that can harness solar energy for their growth and metabolism. These bacteria vary broadly in terms of their metabolism as well as the composition of their photosynthetic apparatus. Unlike oxygenic phototrophic bacteria such as algae and cyanobacteria, APB can use both organic and inorganic electron donors for light-dependent fixation of carbon dioxide without generating oxygen. Their versatile metabolism, ability to adapt in extreme conditions, low maintenance cost and high biomass yield make APB ideal for wastewater treatment, resource recovery and in the production of high value substances. This review highlights the advantages of APB over algae and cyanobacteria, and their applications in photo-bioelectrochemical systems, production of poly-β-hydroxyalkanoates, single-cell protein, biofertilizers and pigments. The ecology of ABP, their distinguishing factors, various physiochemical parameters governing the production of high-value substances and future directions of APB utilization are also discussed.Polysialic acid (polySia) are α2,8- and/or α2,9-linked homopolymers with interesting properties for meningococcal vaccine development or the cure of human neurodegenerative disorders. With the goal to avoid large scale production of pathogenic bacteria, we compare in the current study the efficacy of conventional polySia production to recombinant approaches using the engineered laboratory safety strain E. coli BL21. High cell density cultivation (HCDC) experiments were performed in two different bioreactor systems. Increased cell densities of up to 11.3 (±0.4) g/L and polySia concentrations of up to 774 (±18) mg/L were reached in E. coli K1. However, cultivation of engineered E. coli BL21 strains delivered comparable cell densities but a maximum of only 133 mg/L polySia. Using established downstream procedures, host cell DNA and proteins were removed. All recombinant polySia products showed an identical degree of polymerization >90. Polymers with different glycosidic linkages could be successfully differentiated by nuclear magnetic resonance spectroscopy.In the present paper, we present a substantially revised protocol of the widely used SCGE assay performed under alkaline conditions. In our updated version of the comet assay, which we call the Flash-comet, LiOH is used instead of NaOH during the unwinding and electrophoresis. This allows a higher voltage during the electrophoresis (5 V/cm instead of 0.7 V/cm), making it possible to reduce the unwinding time from 20 to 40 to 2.5 min, and the electrophoresis time from 10 to 20 to 1 min. Still, the Flash-comet was found to detect DNA strand breaks and alkali-labile sites with a higher degree of sensitivity than the conventional protocol in cells that had been exposed to H2O2 or ionizing radiation. In order to prevent alkaline hydrolysis of DNA, the wash and lysis solutions have been modified in the Flash-comet protocol.•By using an alkaline LiOH-based medium, the Flash-comet allows for much shorter times for both unwinding and electrophoresis than the conventional comet assay without compromising the sensitivity.•The reduced run-times of the unwinding and electrophoresis steps in the Flash-comet should also reduce the risk of laboratory-induced alkaline hydrolysis of DNA when evaluating the potential DNA-damaging effects of different types of xenobiotics.The application of dynamic Autoregressive Distributed Lag (dynardl) simulations and Kernel-based Regularized Least Squares (krls) to time series data is gradually gaining recognition in energy, environmental and health economics. The Kernel-based Regularized Least Squares technique is a simplified machine learning-based algorithm with strength in its interpretation and accounting for heterogeneity, additivity and nonlinear effects. The novel dynamic ARDL Simulations algorithm is useful for testing cointegration, long and short-run equilibrium relationships in both levels and differences. Advantageously, the novel dynamic ARDL Simulations has visualization interface to examine the possible counterfactual change in the desired variable based on the notion of ceteris paribus. Thus, the novel dynamic ARDL Simulations and Kernel-based Regularized Least Squares techniques are useful and improved time series techniques for policy formulation.•We customize ARDL and dynamic simulated ARDL by adding plot estimates with confidence intervals.•A step-by-step procedure of applying ARDL, dynamic ARDL Simulations and Kernel-based Regularized Least Squares is provided.•All techniques are applied to examine the economic effect of denuclearization in Switzerland by 2034.• Smart usage of single molecule photobleaching technology and dual-color fluorescence colocalization is of critical importance for exploiting the sensing platform. Here, we provide the detailed protocols related to the article "A split aptamer sensing platform for highly sensitive detection of theophylline based on dual-color fluorescence colocalization and single molecule photobleaching" (published online by Biosensors and Bioelectronics) (Liu et al., 2020). The protocols contain (1) how to clean the slides; (2) how to prepare the probe and detection sample; (3) Single molecule imaging; 4) Data processing by using the Image J. Finally, we used a simple model to confirm the feasibility of the method for integrating dual-color fluorescence colocalization and single molecule photobleaching technology on the theophylline sensing platform. • A simple, ultrasensitive method for the detection of theophylline. • The method is easily comprehensible. • Both strategy formulation and data processing are simple, learnability, and highly reproducible.Local Climate Zones (LCZ) have become a worldwide standard for identifying land cover classes, according to their climate-relevant morphological parameters. The LCZ's are mostly used to evaluate urban climate performance, particularly the relationship between the urban heat island effect (UHI) and the characteristics of the built-up environment. The World Urban Database and Access Portal Tools (WUDAPT) has provided a supervised LCZ classification method based only on moderate resolution free satellite imagery, mostly Landsat 7 or 8 (30 m pixel size, in the visible spectrum brands); however, its' results are less accurate for European cities. Conversely, alternative geographic information system (GIS)-based methods developed so far require information that is hardly available to all, such as building footprints or heights. Here, the ArcGIS based LCZ from Copernicus Toolbox (LCZC) provides an alternative classification method that uses only freely accessible information from the Copernicus Land Monitoring Service (CLMS), being possible to replicate it in 800 European urban locations. The method combines Urban Atlas (UA) and Corine Land Cover (CLC) with Tree Cover Density, Dominant Leaf Type and Grassland information, to produce a higher-resolution baseline shapefile that is classified according to each feature's dominant characteristics. The LCZC toolbox output is a LCZ raster map. It has been validated in five European cities Athens, Barcelona, Lisbon, Marseille, and Naples.•The LCZC toolbox provides an alternative LCZ GIS-based classification, based on freely accessible CLMS datasets.•The use of CLMS shapefile higher-resolution inputs, particularly the UA and CLC datasets, ensures an output LCZ map that has greater detail and higher accuracy.•The availability of CLMS information in 800 European urban areas guarantees that the method can be replicated in those locations.CRISPR-Cas9 gene editing has made it possible to specifically edit genes in a myriad of target cells. Here, a method for isoform-specific editing and clonal selection in Madin-Darby canine kidney (MDCK) epithelial cells is described in detail. This approach was used to address a long-standing question in virology of how adenovirus enters polarized epithelia from the apical surface. Our method relies on selecting two sgRNA sequences, cloning them into a suitable fluorescently labeled Cas9 vector system, and subsequently transfecting our MDCK epithelium and selecting isoform-specific Coxsackievirus and adenovirus receptor knockout clones. Utilization of this method is readily applicable to many other genetic targets in epithelial cells.•Simultaneous utilization of an sgRNA upstream and an sgRNA downstream of a target sequence allows for deletion of the intervening sequence, including whole exons.•Sorting of cells positive for fluorescent marker gene expression enhances the identification of partial and biallelic gene knockout.•PCR screening allows relatively fast and efficient determination of isoform-specific deletion.Adult giant hydronephrosis in a normally sited kidney is unusual during pregnancy. The most frequent cause is congenital obstruction at the ureteropelvic junction. Ultrasound accompanied by magnetic resonance imaging (MRI) are valuable in reaching the diagnosis, especially when clinical assessment of an abdominal mass is inconclusive regarding aetiology. We report a case of giant hydronephrosis in a woman who presented at 23 weeks of gestation with abdominal distension. She was managed conservatively. Unfortunately, the pregnancy was complicated by severe pre-eclampsia at 32 weeks of gestation, necessitating delivery via emergency caesarean section. She had a smooth postpartum recovery, and subsequently standard imaging was performed before nephrectomy. The literature and previously reported cases of giant hydronephrosis in pregnancy are reviewed.Used vehicle crankcase oils are a source of contamination in Caribbean marine environments and may alter the oxidative balance of organism that inhabiting coastal ecosystems. This paper aims to evaluate effects of a water-soluble fraction of used vehicle crankcase oils (WSF-UVCO) on the antioxidant responses of the flame scallop Ctenoides scaber. The organisms were exposed to ascending sublethal concentrations 0, 0.001, 0.01 and 0.1 % of WSF-UVCO in a static system of aquaria during one week. Subsequently activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione-S-transferase (GST) as well as concentrations of reduced glutathione (GSH) and thiobarbituric acid reactive substances (TBARS) were determined in the digestive gland, adductor muscle and gills. SOD, CAT, GST and TBARS increased in digestive gland of organisms exposed to WSF-UVCO at medium and highest concentrations, with a concomitant decrease in GPX and GR activities. In adductor muscle CAT decreased, but GR rose with exposure to 0.01 and 0.1 % WSF-UVCO; in gills, GST rose through all WSF-UVCO concentrations, and SOD, CAT and GR increased only at 0.1 %. The fluctuations in antioxidant enzymes and GST activities point out possible adjustments to control ROS production and detoxification of xenobiotics. These biochemical responses may guarantee the oxidative balance in flame scallop during short term exposure to low concentrations of WSF-UVCO. C. scaber appears suitable as an experimental organism for evaluating biological risks of sublethal exposure to hazardous xenobiotics in tropical marine environments.
This study investigated the effects of co-administration of carbamazepine (CBZ) with grape (
) seed methanolic extract (GSME) on liver toxicity.

Thirty-five male rats (145-155 g) were randomized into 5 groups (n = 7) and administered with propylene glycol (PG 0.1 mL/day), CBZ (25 mg/kg), CBZ (25 mg/kg) + GSME (200 mg/kg), CBZ (25 mg/kg) + GSME (100 mg/kg), or CBZ (25 mg/kg) + GSME (50 mg/kg) orally for 28 days. Twenty-four hours after the last dose, changes in the body weights were determined. The rats were euthanized by cervical dislocation. The liver was weighed and later homogenized; while the supernatant was analyzed biochemically. The liver tissues were preserved in 10 % neutral-buffered formalin for the histomorphological investigation.

There was significant (p = 0.0001) decrease in the body weight following carbamazepine treatment. The relative liver weight also decreased significantly (p = 0.0004) across the treatment group compared with control. The activities of the liver enzymes (aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and glutathione activities), including the concentrations of malondialdehyde, increased significantly (p ≤ 0.0004) following carbamazepine treatment. Various morphological alterations were observed, especially in the photomicrograph of the CBZ treated rats. However, these derangements were attenuated significantly in the CBZ - GSME co-treated group.

This study concludes that GSME treatment may serve as a potential therapeutic agent in carbamazepine-induced hepatotoxicity/ dysfunction.
This study concludes that GSME treatment may serve as a potential therapeutic agent in carbamazepine-induced hepatotoxicity/ dysfunction.Celecoxib is used widely for the acute treatment of pain and for pain relief in various diseases. Furthermore, it shows potential in chemoprevention, although chronic treatment with celecoxib could lead to adverse effects like cardiovascular events. New derivatives of celecoxib were synthesised that may be suitable as chemopreventive agent without inducing adverse effects. Critical endpoint for a safe use of pharmaceuticals is genotoxicity after application. A standard test for the assessment of genotoxicity is the cytokinesis-block micronucleus assay, that evaluates the number micronuclei after treatment of cells with a test compound as biomarker for DNA damage. Various promising derivatives of celecoxib have been assessed with the cytokinesis-block micronucleus assay in HeLa-H2B-GFP cells. It could be demonstrated, that neither celecoxib nor its derivatives were genotoxic in this assay and therefore celecoxib derivatives could be developed further for a safe use as chemopreventive agent.In recent years 3D-bioprinting technology has been developed as an alternative to animal testing. It possesses a great potential for in vitro testing as it aims to mimic human organs and physiology. In the present study, an alginate-gelatin-Matrigel based hydrogel was used to prepare 3D-bioprinted HepaRG cultures using a pneumatic extrusion printer. These 3D models were tested for viability and metabolic functions. Using 3D-bioprinted HepaRG cultures, we tested the toxicity of aflatoxin B1 (10 or 20 μM) in vitro and compared the results with 2D HepaRG cultures. There was a dose-dependent toxicity effect on cell viability, reduction of metabolic activity and albumin production. We found that 3D-bioprinted HepaRG cultures are more resistant to aflatoxin B1 treatment than 2D cultures. Although the metabolic activities were reduced upon treatment with aflatoxin B1, the 3D models were still viable and survived longer, up to 3 weeks, than the 2D culture, as visualized by fluorescence microscopy. Furthermore, albumin production recovered slightly in 3D models after one and two weeks of treatment. Taken together, we consider using 3D-bioprinting technology to generate 3D tissue models as an alternative way to study toxicity in vitro and this could also provide a suitable alternative for chronic hepatotoxicity studies in vitro.Glyoxal (GO), a by-product of glucose auto-oxidation, is involved in the glycation of proteins/ lipids and formation of advanced glycation (AGE) and lipoxidation (ALE) end products. AGE/ALE were shown to contribute to diabetic complications development/progression such as nephropathy. Diabetic nephropathy progression has an oxidative nature. Given the antioxidant effects of polyphenols, potential protective effects of resveratrol, curcumin and gallic acid, in rat renal cells treated with GO, were evaluated in the present work. According to our results, incubation of GO with the cells reduced their viability and led to membrane lysis, reactive oxygen species (ROS) formation, lipid peroxidation, mitochondrial membrane potential collapse, and lysosomal membrane leakage. These findings were prevented by pre-treatment with resveratrol, curcumin and gallic acid. Mitochondrial and lysosomal toxic interactions appear to worsen oxidative stress/cytotoxicity produced by GO. Resveratrol, curcumin and gallic acid inhibited ROS formation and attenuated GO-induced renal cell death.Renal cell carcinoma (RCC) a common malignancy with potential to metastasize to visceral organs. However, it uncommonly spreads to the lower genitourinary tract. We present a man with a history of RCC status post radical nephrectomy in April 2012. He presented 8 years later with obstructive lower urinary tract symptoms and an elevated prostate specific antigen (PSA). Further imaging showed a large enhancing mass with internal blood vessels posterior to the left prostate and seminal vesicle. A prostate biopsy was performed and consistent with metastatic RCC. He was ultimately treated with immunotherapy and focal stereotactic radioablation.Ewing sarcoma (ES) is an entity which belongs to a spectrum of neoplastic diseases called the Ewing sarcoma family of tumors (EFT). EFTs of the kidney represent less than 1% of all renal tumors. Herein, we presented a case of primary renal ES with tumor thrombosis up to vena cava who underwent radical nephrectomy and IVC tumor thrombectomy followed by adjuvant chemotherapy. Histopathology showed that the tumor composed of small uniform, dark, round cells arranged in sheets, and rosettoid pattern. The diagnosis of ESFT was confirmed by detecting EWS/FLI-1 fusion gene using reverse transcription polymerase chain reaction (RT-PCR).Inserting Double-j ureteral stent is one of the most popular procedures in urology field. There are different indications for indwelling the stent. For some reasons, it could be neglected for a long time despite its importance. We present a case of 52-year-old patient who had a missed fragment of stent in the urinary bladder for two years with stone formation on one end. We successfully removed the stent and the stone. Such a case is considered rare to deal with during urology practice.Pregnancy presents unique obstacles to diagnosis and management of urologic disease. We present a case of a primigravid female with clot retention requiring evacuation in the operating room due to the avulsion of a bladder mass which prolapsed during labor. Tumor pathology demonstrated a low-grade spindle cell lesion positive for progesterone receptor (PR) and high mobility group A2 (HMGA2), suggestive of deep angiomyxoma versus a benign fibroepithelial polyp or inflammatory myofibroblastic tumor.Renal Cell Carcinoma (RCC) corresponds to 3% of the neoplasms in the adults. Surgery is the main mode of treatment, which can be associated toretroperitoneal lymphadenectomy in the presence of clinically tumor positive lymph nodes. Castleman Disease (CD) is a rare lymphoproliferative disorder, with little-known etiopathogenesis. It rarely affects the retroperitoneum. Thorax, neck, and abdomen are more frequently affected. Therefore, CD can simulate lymphatic spread from RCC to the retroperitoneum, also leading to a possible misdiagnosis, or diagnosis concerning a paraneoplastic syndrome due to RCC.Urethral injuries occurring during pelvic trauma can cause a heavy morbidity and negative impact for the quality of life of a child. We present a case of a 7 years old boy with a complete posterior urethral disruption managed with a successful realignment by a unique modification of the "rendez vous" technique with the simultaneous performance of both antegrade flexible and a retrograde rigid cystoscopy.We highlight the case of a 12 year old male who presented after sustaining a gunshot injury to the scrotum resulting in testicular, prostatic, and urethral transection in addition to pelvic fracture, extra peritoneal bladder injury, and transmural injury to recto sigmoid and ileum. The patient underwent a left orchiectomy, primary repair of the bladder and urethra, placement of universal plate on superior pubic rami, and segmental rectosigmoid and ileum resection. These findings illustrate the collaborative efforts of trauma surgery and urology to treat complex lower genitourinary (GU) injuries and how the direct prioritization of surgical efforts provides acceptable outcomes.3-methylglutaconic aciduria type 1 (3-MGA-I) (MIM ID #250950) is an ultra-rare, autosomal recessive organic aciduria, resulting from mutated AUH gene, leading to the deficient 3-methylglutaconyl-CoA hydratase (3-MGH). Only around 40 cases are previously reported, caused by a spectrum of 10 mutations. The clinical spectrum of 3-MGA-I in children is heterogeneous, varying from asymptomatic individuals to mild neurological impairment, speech delay, quadriplegia, dystonia, choreoathetoid movements, severe encephalopathy, psychomotor retardation, basal ganglia involvement. Early dietary treatment with leucine restriction and carnitine supplementation may be effective in improving neurological state in pediatric patients with 3-MGA-I. We presented a girl with 3-MGA-I due to novel AUH gene mutation (homozygous variant c.330 + 5G > A) and confirmed by almost undetectable 3-MGH-enzyme activity, who initially presented with central precocious puberty at an early age of 4.5 years. Precocious puberty might be associated with the 3-MGA-I, as is reported previously in some other metabolic disorders that result in pathologic accumulation of metabolites or toxic brain damage. Therapy with GnRH agonist triptorelin effectively arrested pubertal development.Inherited muscle disorders are caused by pathogenic changes in numerous genes. Herein, we aimed to investigate the etiology of muscle disease in 24 consecutive Greek patients with myopathy suspected to be genetic in origin, based on clinical presentation and laboratory and electrophysiological findings and absence of known acquired causes of myopathy. Of these, 16 patients (8 females, median 24 years-old, range 7 to 67 years-old) were diagnosed by Whole Exome Sequencing as suffering from a specific type of inherited muscle disorder. Specifically, we have identified causative variants in 6 limb-girdle muscular dystrophy genes (6 patients; ANO5, CAPN3, DYSF, ISPD, LAMA2, SGCA), 3 metabolic myopathy genes (4 patients; CPT2, ETFDH, GAA), 1 congenital myotonia gene (1 patient; CLCN1), 1 mitochondrial myopathy gene (1 patient; MT-TE) and 3 other myopathy-associated genes (4 patients; CAV3, LMNA, MYOT). In 6 additional family members affected by myopathy, we reached genetic diagnosis following identification of a causative variant in an index patient. In our patients, genetic diagnosis ended a lengthy diagnostic process and, in the case of Multiple acyl-CoA dehydrogenase deficiency and Pompe's disease, it enabled specific treatment to be initiated. These results further expand the genotypic and phenotypic spectrum of inherited myopathies.
Mucopolysaccharidosis type IV A (MPS IVA) or Morquio A syndrome is an autosomal recessive lysosomal storage disease caused by
gene mutations that lead to a deficiency of the
-acetylgalactosamine-6-sulfate sulfatase enzyme and the accumulation of two glycosaminoglycans in cell lysosomes, namely, chondroitin and keratan sulfate.

To present two female patients with Morquio A syndrome in their late adult years (over 50 years of age) with a classical phenotype, treated with enzyme replacement therapy; and to present a summary of the natural history and the characteristics of the disease, and the benefit of comprehensive management.

Descriptive clinical study before and after the treatment with enzyme replacement therapy as part of the comprehensive management of MPS IVA.

Enzyme replacement therapy with elosulfase alfa was effective, with an adequate safety profile in these two patients, showing evidence of sustained improvement in terms of endurance and gait patterns.

We present two cases of MPS IVAsulfase alfa as part of comprehensive management has been crucial; we suspect a clinical response and infer a better quality of life and reduced burden for the caregiver, supporting its use in older patients.A 57-year-old Australian woman, with a history of hazardous alcohol consumption, presented with a seizure following 2 days of fever and headache. Initial imaging suggested the presence of an isolated brain abscess, however, a thorough physical examination, identified no additional septic focus. Five sets of blood cultures were sterile and serology for Burkholderia pseudomallei was negative. Other investigations including computed tomography of her chest, abdomen and pelvis and a trans-esophageal echocardiogram were normal. Despite the administration of intravenous vancomycin, ceftriaxone, and metronidazole, her condition deteriorated. At emergency craniotomy, the abscess was drained and B. pseudomallei was cultured, confirming a diagnosis of melioidosis. She received 8 weeks of intravenous meropenem, combined with oral trimethoprim/sulfamethoxazole; the trimethoprim/sulfamethoxazole was continued for a total of 12 months. She recovered completely and was able to return to full-time work. Melioidosis, is endemic to Australia and South East Asia and, globally, is estimated to kill 89,000 every year. It can affect almost any organ, but up to 5% have central nervous system (CNS) involvement, where it may present as an encephalomyelitis, brain abscess or meningitis. B. pseudomallei is resistant to many commonly used antibiotics and even in well-resourced settings the case-fatality rate of CNS infection may rise to 50 %. This patient lived in a melioid-endemic region, and, with hazardous alcohol consumption, had a classical risk factor for the disease, but the sterile blood cultures and negative B. pseudomallei serology delayed definitive therapy. Despite the delayed diagnosis, definitive drainage and prolonged anti-bacterial therapy ensured a complete recovery.Arcanobacterium haemolyticum is an extremely rare cause of cerebral abscess. We present a unique case of Arcanobacterium haemolyticum sinusitis complicated by preseptal cellulitis and cerebral abscess. The patient initially presented with pharyngitis and then developed sinus congestion, headache and facial pain. Computed tomography and magnetic resonance imaging revealed a right gyrus rectus cerebral abscess and paranasal sinus infection. The patient underwent endoscopic sinus surgery and cultures revealed Arcanobacterium haemolyticum. Repeat imaging revealed maturation and progression of intracranial abscess. The abscess was drained and patient was treated with parenteral and oral antibiotics until complete clinical and radiological remission. This case highlights the importance of recognizing Arcanobacterium haemolyticum as a cause of invasive disease in immunocompetent hosts.Tuberculosis can involve the hematological system and cause anemia, leucopenia, leukocytosis, thrombocytopenia, and thrombocytosis. Immune thrombocytopenia related to tuberculosis is rare. We present a case of a 54 years old male patient who was evaluated for isolated asymptomatic thrombocytopenia discovered on routine laboratory investigations. Work up was positive for disseminated tuberculosis. The patient responded to a tapering dose of steroids and anti-tuberculous medications with significant and persistent platelet count improvement.Severe infection with human adenovirus (HAdV) is uncommon in adults, and the lack of reliable point-of-care testing makes the diagnosis challenging. A 39-year-old immunocompetent Indian man developed severe pneumonia, and his condition became life-threatening despite antimicrobial therapy. While sputum and blood cultures remained negative, a multiplex PCR respiratory panel (Filmarray Respiratory Panel), which is only approved for use with nasopharyngeal samples, detected HAdV in the serum and tracheal aspirates on day 5. We therefore initiated ganciclovir, steroids, and intravenous immunoglobulin. The patient's respiratory condition improved significantly, and he eventually recovered without complications. We later confirmed that conventional PCR of serum detected HAdV-B7. Our case illustrated that a respiratory panel using multiplex PCR successfully detected HAdV in unapproved samples. Such off-label analyses may support the early diagnosis of infections caused by pathogens that are difficult to identify by routine microbiological examination.D. repens is the causative agent of subcutaneous dirofilariasis in canine animals. In recent years, human invasion by this vector-borne helminthiasis has been recorded in many countries with temperate climate, but the localization of this helminth in the cavities of the human body is extremely rare. Cases of atypical localization of D. repens are described in the organs of the chest, cervical lymph node, in the spermatic cord and epididymis. It is usually requires differential diagnosis with neoplastic or metastatic processes. We report a case of the detection of Dirofilaria repens in the right inguinal lymph node in a 56-year-old woman. Helminth was identified by parasitological and molecular biological methods. A morphological study of cross sections of the nematode in histological preparations and molecular biological method, the polymerase chain reaction (PCR) of scrapings of histological material, were used in parallel.A 52-year-old woman with right-sided breast cancer was diagnosed with a left pulmonary arteriovenous malformation (PAVM) by computed tomography (CT). Percutaneous embolization of the PAVM after treatment of the breast cancer was scheduled to prevent a paradoxical embolic event. She underwent lumpectomy, followed by systemic chemotherapy in combination with tangential field radiotherapy. Subsequently, she received endocrine therapy with tamoxifen, anastrozole, and exemestane, sequentially. There was no change in the PAVM on CT performed during the administration of anastrozole. Subsequently, CT performed five months after switching to exemestane showed obviously decreased size of the affected vessels, and the sac had almost disappeared. To the best of our knowledge, this is the first case report to describe the spontaneous regression of a PAVM during endocrine therapy for breast cancer.The genetic disorder alpha 1 antitrypsin deficiency (AATD) results in reduced levels of alpha 1 antitrypsin (AAT) in the lung and an imbalance between AAT anti-protease activity and the activity of proteases that degrade elastin and connective tissues. This imbalance commonly leads to the excessive proteolysis of structural tissue of the alveoli, causing chronic obstructive pulmonary disease (COPD)/emphysema. While patients with AATD are encouraged to make lifestyle changes, including stopping smoking, and can be treated with alpha 1 antitrypsin therapy (AAT therapy) to slow progression of COPD/emphysema, damage to the lungs is irreparable, and therefore, lung transplantation is required in severe cases. However, following lung transplant, the genetic cause of AATD-related COPD/emphysema remains, and patients may continue to be at risk of redeveloping COPD/emphysema. Recurrence of COPD/emphysema was observed in a patient with AATD 2 years after initial successful lung transplantation and cessation of AAT therapy who recommenced smoking after no signs of disease at the 1-year assessment. This case demonstrates that smoking cessation is critical in patients with AATD, even after lung transplant, and it highlights that patients with AATD may benefit from AAT therapy post-lung transplant.
Voice training induced spontaneous pneumothorax is seldom reported in the literature. This study reports a case of middle-aged man without comorbidities who presented with spontaneous pneumothorax following voice training and made a complete recovery after CT guided needle thoracostomy.

This is a case of a middle-aged male non-smoker with ectomorphic build who presented with chest pain of sudden onset and difficulty in breathing following voice training. The chest pain was central, radiated to the left shoulder and aggravated by lying supine. Chest auscultation revealed reduced breath sounds on the left middle and lower lung zones posteriorly.An initial diagnosis of chest pain of unknown origin was made. Chest radiograph done revealed a left sided pneumothorax, with no background lung pathology seen. Chest CT was done to rule out any underlying pathology, to quantify the pneumothorax and to plan for CT guided needle thoracostomy at our institution.Complete resolution of the left sided pneumothorax was seen after the procedure.

Voice training is a rare cause of primary spontaneous pneumothorax. In the absence of any other lung pathology, it can be effectively managed by CT guided needle thoracostomy as seen in the index patient.It is essential for emergency physicians to include voice training as a potential cause for primary spontaneous pneumothorax.
Voice training is a rare cause of primary spontaneous pneumothorax. In the absence of any other lung pathology, it can be effectively managed by CT guided needle thoracostomy as seen in the index patient.It is essential for emergency physicians to include voice training as a potential cause for primary spontaneous pneumothorax.Paragonimiasis, or Oriental lung fluke is a parasitic infestation seen in Asia, Africa and South America which is spread by the consumption of crabs and crayfish. To date four cases have been reported from Nepal. Here, we report a case of paragonimiasis in a young male from Kathmandu valley who presented with symptoms of fever, on and off for 1 month, shortness of breath and cough. He was found to have pleural effusion. Sputum examination did not reveal acid fast bacilli, However, based on clinical features, he was started on antitubercular treatment. There was initial improvement, but later, he continued to have cough and hemoptysis over the next 2 years and on subsequent High-Resolution Computerized Tomography (HRCT) he was found to have a cavitary lung lesion in the superior segment of lower lobe of left lung. A possibility of aspergillosis was considered for which he underwent a lobectomy. The gross examination of the lung showed a small cavity measuring 5 mm which revealed on histology a parasitic structure with serous glands within it. In addition, there were many foreign body granulomas with ova within them. A diagnosis of paragonimiasis was made and the patient was started on Praziquantal. He recovered well and is currently asymptomatic. We can learn from this case that the signs and symptoms of paragonimiasis mimic that of tuberculosis and the mistaken diagnosis can lead to unnecessary treatment, prolonged morbidity and loss of time and resources.Collision tumors are rare entities that consist of at least two or more histologically and ontologically distinct tumor types within the same organ. It is still not well understood how collision tumors form; yet, three main theories have been proposed to explain the pathogenesis, including the "random collision effect," "field cancerization," and "tumor-to-tumor carcinogenesis." Collision tumors have been encountered in various body organs, including the lung. They either consist of a metastasizing tumor colliding with primary cancer or distinct primary or metastatic cancers colliding together. Here, we describe a rare case of collision tumors of the lung that consists of two metastatic carcinomas, namely renal cell carcinoma and urothelial carcinoma of the bladder. We propose that the urothelial carcinoma disseminated into several pre-existing pulmonary metastases of renal cell carcinoma with heterotopic bone formation. The possible mechanisms underlying the development of this peculiar tumor are discussed.
Bone involvement in Multiple Myeloma results from increased osteoclast formation and activity that occurs in proximity to myeloma cells. The role of Alkaline Phosphatse (ALP) in this process and the diagnostic significance of plasma levels in patients with MM are unclear.

To compare plasma ALP levels in patients with MM and solid cancers and metastatic lesions to the bone.

In this observational retrospective study we enrolled 901 patients were enrolled 440 patients (49%) with Multiple Myeloma, 461 (51%) with solid cancers. All 901 patients had bone lesions. Among patients with Multiple Myeloma, ALP values were mainly in the range of normality than those observed in patients with solid cancers and bone lesions. This difference is independent of stage, number and type of bone lesions.

This study suggests that plasma ALP has a different clinical significance in MM than in other neoplasms and could be used as a discriminating marker in presence of bone lesions. In particular, lower or normal values, should suggest further investigations such as urinary and serum electrophoresis, associated with bone marrow aspirate in case of the presence of a monoclonal component, in order to confirm or exclude a MM diagnosis.
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