Diabetic microenvironment deteriorates the regenerative capacities of adipose mesenchymal stromal cells.

BACKGROUND: Type 2 diabetes is an endocrine disorder characterized by compromised insulin sensitivity that eventually leads to overt disease. Adipose stem cells (ASCs) showed promising potency in improving type 2 diabetes and its complications through their immunomodulatory and differentiation capabilities. However, the hyperglycaemia of the diabetic microenvironment may exert a detrimental effect on the functionality of ASCs. Herein, we investigate ASC homeostasis and regenerative potential in the diabetic milieu. METHODS: We conducted data collection and functional enrichment analysis to investigate the differential gene expression profile of MSCs in the diabetic microenvironment. Next, ASCs were cultured in a medium containing diabetic serum (DS) or normal non-diabetic serum (NS) for six days and one-month periods. Proteomic analysis was carried out, and ASCs were then evaluated for apoptosis, changes in the expression of surface markers and DNA repair genes, intracellular oxidative stress, and differentiation capacity. The crosstalk between the ASCs and the diabetic microenvironment was determined by the expression of pro and anti-inflammatory cytokines and cytokine receptors. RESULTS: The enrichment of MSCs differentially expressed genes in diabetes points to an alteration in oxidative stress regulating pathways in MSCs. Next, proteomic analysis of ASCs in DS revealed differentially expressed proteins that are related to enhanced cellular apoptosis, DNA damage and oxidative stress, altered immunomodulatory and differentiation potential. Our experiments confirmed these data and showed that ASCs cultured in DS suffered apoptosis, intracellular oxidative stress, and defective DNA repair. Under diabetic conditions, ASCs also showed compromised osteogenic, adipogenic, and angiogenic differentiation capacities. Both pro- and anti-inflammatory cytokine expression were significantly altered by culture of ASCs in DS denoting defective immunomodulatory potential. Interestingly, ASCs showed induction of antioxidative stress genes and proteins such as SIRT1, TERF1, Clusterin and PKM2. CONCLUSION: We propose that this deterioration in the regenerative function of ASCs is partially mediated by the induced oxidative stress and the diabetic inflammatory milieu. The induction of antioxidative stress factors in ASCs may indicate an adaptation mechanism to the increased oxidative stress in the diabetic microenvironment.

The cross talk between type II diabetic microenvironment and the regenerative capacities of human adipose tissue-derived pericytes: a promising cell therapy.

BACKGROUND: Pericytes (PCs) are multipotent contractile cells that wrap around the endothelial cells (ECs) to maintain the blood vessel's functionality and integrity. The hyperglycemia associated with Type 2 diabetes mellitus (T2DM) was shown to impair the function of PCs and increase the risk of diabetes complications. In this study, we aimed to investigate the deleterious effect of the diabetic microenvironment on the regenerative capacities of human PCs. METHODS: PCs isolated from human adipose tissue were cultured in the presence or absence of serum collected from diabetic patients. The functionality of PCs was analyzed after 6, 14, and 30 days. RESULTS: Microscopic examination of PCs cultured in DS (DS-PCs) showed increased aggregate formation and altered surface topography with hyperbolic invaginations. Compared to PCs cultured in normal serum (NS-PCs), DS-PCs showed more fragmented mitochondria and thicker nuclear membrane. DS caused impaired angiogenic differentiation of PCs as confirmed by tube formation, decreased VEGF-A and IGF-1 gene expression, upregulated TSP1, PF4, actin-related protein 2/3 complex, and downregulated COL21A1 protein expression. These cells suffered more pronounced apoptosis and showed higher expression of Clic4, apoptosis facilitator BCl-2-like protein, serine/threonine protein phosphatase, and caspase-7 proteins. DS-PCs showed dysregulated DNA repair genes CDKN1A, SIRT1, XRCC5 TERF2, and upregulation of the pro-inflammatory genes ICAM1, IL-6, and TNF-α. Further, DS-treated cells also showed disruption in the expression of the focal adhesion and binding proteins TSP1, TGF-ß, fibronectin, and PCDH7. Interestingly, DS-PCs showed resistance mechanisms upon exposure to diabetic microenvironment by maintaining the intracellular reactive oxygen species (ROS) level and upregulation of extracellular matrix (ECM) organizing proteins as vinculin, IQGAP1, and tubulin beta chain. CONCLUSION: These data showed that the diabetic microenvironment exert a deleterious effect on the regenerative capacities of human adipose tissue-derived PCs, and may thus have possible implications on the vascular complications of T2DM. Nevertheless, PCs have shown remarkable protective mechanisms when initially exposed to DS and thus they could provide a promising cellular therapy for T2DM.

Phages for treatment of Klebsiella pneumoniae infections.

Klebsiella pneumoniae is an opportunistic pathogen involved in both hospital- and community-acquired infections. K. pneumoniae is associated with various infections, including pneumonia, septicemia, meningitis, urinary tract infection, and surgical wound infection. K. pneumoniae possesses serious virulence, biofilm formation ability, and severe resistance to many antibiotics especially hospital-acquired strains, due to excessive use in healthcare systems. This limits the available effective antibiotics that can be used for patients suffering from K. pneumoniae infections; therefore, alternative treatments are urgently needed. Bacteriophages (for short, phages) are prokaryotic viruses capable of infecting, replicating, and then lysing (lytic phages) the bacterial host. Phage therapy exhibited great potential for treating multidrug-resistant bacterial infections comprising K. pneumoniae. Hence, this chapter emphasizes and summarizes the research articles in the PubMed database from 1948 until the 15th of December 2022, addressing phage therapy against K. pneumoniae. The chapter provides an overview of K. pneumoniae phages covering different aspects, including phage isolation, different morphotypes of isolated phages, in vitro characterization, anti-biofilm activity, various therapeutic forms, in vivo research and clinical studies.

Morphological, biological, and genomic characterization of Klebsiella pneumoniae phage vB_Kpn_ZC2.

BACKGROUND: Bacteriophages (phages) are one of the most promising alternatives to traditional antibiotic therapies, especially against multidrug-resistant bacteria. Klebsiella pneumoniae is considered to be an opportunistic pathogen that can cause life-threatening infections. Thus, this study aims at the characterization of a novel isolated phage vB_Kpn_ZC2 (ZCKP2, for short). METHODS: The phage ZCKP2 was isolated from sewage water by using the clinical isolate KP/08 as a host strain. The isolated bacteriophage was purified and amplified, followed by testing of its molecular weight using Pulse-Field Gel Electrophoresis (PFGE), transmission electron microscopy, antibacterial activity against a panel of other Klebsiella pneumoniae hosts, stability studies, and whole genome sequencing. RESULTS: Phage ZCKP2 belongs morphologically to siphoviruses as indicated from the Transmission Electron Microscopy microgram. The Pulsed Field Gel Electrophoresis and the phage sequencing estimated the phage genome size of 48.2 kbp. Moreover, the absence of lysogeny-related genes, antibiotic resistance genes, and virulence genes in the annotated genome suggests that phage ZCKP2 is safe for therapeutic use. Genome-based taxonomic analysis indicates that phage ZCKP2 represents a new family that has not been formally rated yet. In addition, phage ZCKP2 preserved high stability at different temperatures and pH values (-20 - 70 °C and pH 4 - 9). For the antibacterial activity, phage ZCKP2 maintained consistent clear zones on KP/08 bacteria along with other hosts, in addition to effective bacterial killing over time at different MOIs (0.1, 1, and 10). Also, the genome annotation predicted antibacterial lytic enzymes. Furthermore, the topology of class II holins was predicted in some putative proteins with dual transmembrane domains that contribute significantly to antibacterial activity. Phage ZCKP2 characterization demonstrates safety and efficiency against multidrug-resistant K. pneumoniae, hence ZCKP2 is a good candidate for further in vivo and phage therapy clinical applications.

The Lytic Activity of Bacteriophage ZCSE9 against Salmonella enterica and Its Synergistic Effects with Kanamycin.

Salmonella, the causative agent of several diseases in humans and animals, including salmonellosis, septicemia, typhoid fever, and fowl typhoid, poses a serious threat to global public health and food safety. Globally, reports of therapeutic failures are increasing because of the increase in bacterial antibiotic resistance. Thus, this work highlights the combined phage-antibiotic therapy as a promising approach to combating bacterial resistance. In this manner, the phage ZCSE9 was isolated, and the morphology, host infectivity, killing curve, combination with kanamycin, and genome analysis of this phage were all examined. Morphologically, phage ZCSE9 is a siphovirus with a relatively broad host range. In addition, the phage can tolerate high temperatures until 80 °C with one log reduction and a basic environment (pH 11) without a significant decline. Furthermore, the phage prevents bacterial growth in the planktonic state, according to the results of the time-killing curve. Moreover, using the phage at MOI 0.1 with kanamycin against five different Salmonella serotypes reduces the required antibiotics to inhibit the growth of the bacteria. Comparative genomics and phylogenetic analysis suggested that phage ZCSE9, along with its close relatives Salmonella phages vB_SenS_AG11 and wksl3, belongs to the genus Jerseyvirus. In conclusion, phage ZCSE9 and kanamycin form a robust heterologous antibacterial combination that enhances the effectiveness of a phage-only approach for combating Salmonella.

The interplay of cells, polymers, and vascularization in three-dimensional lung models and their applications in COVID-19 research and therapy.

Millions of people have been affected ever since the emergence of the corona virus disease of 2019 (COVID-19) outbreak, leading to an urgent need for antiviral drug and vaccine development. Current experimentation on traditional two-dimensional culture (2D) fails to accurately mimic the in vivo microenvironment for the disease, while in vivo animal model testing does not faithfully replicate human COVID-19 infection. Human-based three-dimensional (3D) cell culture models such as spheroids, organoids, and organ-on-a-chip present a promising solution to these challenges. In this report, we review the recent 3D in vitro lung models used in COVID-19 infection and drug screening studies and highlight the most common types of natural and synthetic polymers used to generate 3D lung models.

Influenza vaccine effect on risk of stroke occurrence: a systematic review and meta-analysis.

Background: Stroke is a significant global cause of mortality and long-term disability, potentially influenced by infections that heighten systemic inflammation and thrombotic events. The full impact of influenza vaccination on stroke remains uncertain. This systematic review and meta-analysis aimed to investigate the association between influenza immunization and stroke incidence. Methods: We searched for randomized controlled trials (RCTs), case-control, and cohort studies published in PubMed/Medline, Cochrane-Central-Register-of-Controlled-Trials (CENTRAL), and Embase until 5 December 2022, and identified articles investigating the effect of influenza vaccine on stroke occurrence. All articles were screened by two independent reviewers. We performed a meta-analysis to investigate the risk of stroke occurrence in vaccinated vs. unvaccinated individuals. The random-effects model was used in all statistical analyses. Results: Among the 26 articles meeting our criteria, 10 were retrospective cohort studies, 9 were case-control studies, 3 were prospective cohort studies, 3 were RCTs and 1 case-series. Overall, the studies showed a significant decrease in the risk of stroke incidence/hospitalization among vaccinated patients (OR = 0.81, 95% CI [0.77-0.86], p = 0.00001). Furthermore, studies showed flu vaccine decreases the occurrence of mortality among stroke patients (OR = 0.50, 95% CI [0.37-0.68], p = 0.00001). Sub-group analysis revealed significant protective effect for patients with specific comorbidities including atrial fibrillation (OR = 0.68, 95% CI [0.57-0.81], p = 0.0001), diabetes (OR = 0.76, 95% CI [0.66-0.87], p = 0.0001), Chronic obstructive pulmonary disease (OR = 0.70, 95% CI [0.61-0.81], p = 0.00001), and hypertension (OR = 0.76, 95% CI [0.70-83], p = 0.00001). Conclusion: The current meta-analysis further supports prior findings that influenza vaccination reduces stroke risk, particularly in patients with comorbidities. Guidelines should promote vaccination for at-risk individuals.

Topically Applied Bacteriophage to Control Multi-Drug Resistant Klebsiella pneumoniae Infected Wound in a Rat Model.

(Background): Multi-drug-resistant Klebsiella pneumoniae (MDR-KP) has steadily grown beyond antibiotic control. Wound infection kills many patients each year, due to the entry of multi-drug resistant (MDR) bacterial pathogens into the skin gaps. However, a bacteriophage (phage) is considered to be a potential antibiotic alternative for treating bacterial infections. This research aims at isolating and characterizing a specific phage and evaluate its topical activity against MDR-KP isolated from infected wounds. (Methods): A lytic phage ZCKP8 was isolated by using a clinical isolate KP/15 as a host strain then characterized. Additionally, phage was assessed for its in vitro host range, temperature, ultraviolet (UV), and pH sensitivity. The therapeutic efficiency of phage suspension and a phage-impeded gel vehicle were assessed in vivo against a K. pneumoniae infected wound on a rat model. (Result): The phage produced a clear plaque and was classified as Siphoviridae. The phage inhibited KP/15 growth in vitro in a dose-dependent pattern and it was found to resist high temperature (˂70 °C) and was primarily active at pH 5; moreover, it showed UV stability for 45 min. Phage-treated K. pneumoniae inoculated wounds showed the highest healing efficiency by lowering the infection. The quality of the regenerated skin was evidenced via histological examination compared to the untreated control group. (Conclusions): This research represents the evidence of effective phage therapy against MDR-KP.

GIS-Based Analysis Framework to Identify the Determinants of COVID-19 Incidence and Fatality in Africa.

Corona virus diseases 2019 (COVID-19) pandemic is an extraordinary threat with significant implications in all aspects of human life; therefore, it represents the most immediate challenge for the countries all over the world. This study, hence, is intended to identify the best GIS-based model that can explore, quantify, and model the determinants of COVID-19 incidence and fatality. For this purpose, geospatial models were developed to estimate COVID-19 incidence and fatality rates in Africa, up to 16th of August 2020 at the national level. The models involved Ordinary Least Squares (OLS) and Geographically Weighted Regression (GWR) analysis using ArcGIS. Spatial autocorrelation analysis recorded a positive spatial autocorrelation in COVID-19 incidence (Moran index 0.16, P = 0.1) and fatality (Moran index 0.26, P = 0.01) rates within different African countries. GWR model had higher R2 than OLS for prediction of incidence and mortality (58% vs 45% and 55% vs 53%). The main predictors of COVID-19 incidence rate were overcrowding, health expenditure, HIV infections, air pollution, and BCG vaccination (mean ß = 3.10, 1.66, 0.01, 3.79, and -66.60 respectively, P < 0.05). The main determinants of COVID-19 fatality were prevalence of bronchial asthma, tobacco use, poverty, aging, and cardiovascular diseases fatality (mean ß = 0.00162, 0.00004, -0.00025, -0.00144, and -0.00027 respectively, P < 0.05). Application of the suggested model can assist in guiding intervention strategies, particularly at the local and community level whenever the data on COVID-19 cases and predictors variables are available.

Based Analysis Framework for identifying COVID-19 Incidence and Fatality Determinants at National Level Case study: Africa

BackgroundCOVID-19 pandemic is an extraordinary threat with significant implications in all aspects of human life, therefore, it represents the most immediate challenges for all countries all over the world. ObjectivesThis study is intended to develop a GIS-based analysis model to explore, quantify and model the relationships between COVID-19 morbidity and mortality and their potential predictor variables. MethodFor this purpose, a model was developed to estimate COVID-19 incidence and fatality rates in Africa up to 16th of August 2020 at the national level. The model involved Ordinary Least Squares (OLS) and Geographically Weighted Regression (GWR) analysis through ArcGIS was applied. ResultSpatial Autocorrelation Analysis revealed that there was positive spatial autocorrelation in COVID-19 incidence (Moran index 0.16. P value <0.1), and fatality (Moran index 0.0.35, P value<0.01) rates within different African countries. At continental level, OLS revealed that COVID-19 incidence rate was found to be positively associated with overcrowding, health expenditure, HIV infections and air pollution and negatively associated with BCG vaccine ({beta}=2.97,1.45, 0.01, 3.29, -47.65 respectively, P< 0.05) At the same time, COVID-19 fatality was found to be positively related to asthma prevalence and tobacco use. Yet, certain level of inconsistency was noted in the case of COVID-19 fatality, which was negatively related to elder population, poverty, and cardiovascular mortality (P<0.05). This model showed convenient level of validity in modeling the relationship between COVID-19 incidence as well as fatality and their key predictors using GWR. In this respect, the model explained about 58% and 55% of the variance in COVID-19 incidence and fatality rates, respectively, as a function of considered predictors. ConclusionApplication of the suggested model can assist in guiding intervention strategies, particularly in case of local and community level whenever the data on COVID-19 cases and predictors variables are available.

Human Adipose-Derived Pericytes: Biological Characterization and Reprogramming into Induced Pluripotent Stem Cells.

BACKGROUND/AIMS: Pericytes (PCs) are multipotent vascular precursors that play a critical physiological role in the development and maintenance of blood vessel integrity. In this study, we aim to characterize PCs isolated from human abdominal adipose tissue and develop an integration-free induced pluripotent stem cells (iPSCs) using episomal vectors. METHODS: The ultrastructure of adipose tissue-derived PCs was determined using scanning and transmission electron microscopy. The expression of mesenchymal stem cells (MSCs) and pericyte markers were examined using flow cytometry and PCR analysis. PCs were induced to adipogenic, osteogenic and myogenic lineages, and their angiogenic potential was determined using tube formation assay. We further established pericyte reprogramming protocol using episomal vectors. RESULTS: Our data showed that human adipose tissue-derived PCs uniformly expressed MSCs, CD105 and CD73, and PCs markers, desmin, and alpha smooth muscle actin (α-SMA), while lacked the expression of HLA-DR and the hematopoietic markers CD34, CD11b and CD45. Ultrastructure analysis showed typical internal structure for the PCs with a characteristic prominent eccentric nuclei and cytoplasmic invaginations forming a caveolar system. Functional analysis showed efficient differentiation into adipocytes, osteocytes, and myocyte-like cells. Adipose tissue-derived PCs showed angiogenic potential using tube-forming assay. To determine further application of these cells for personalized therapy, we reprogrammed PCs into induced pluripotent stem cells (iPSCs) using episomal vectors. Reprogrammed cells gradually lost their fusiform shape, acquired the epithelial cell morphology and formed colonies. Furthermore, reprogrammed cells successfully expressed the pluripotency markers OCT4, Nanog, SSEA-4, and ß-catenin, an early reprogramming marker. CONCLUSION: The accessibility and abundance of human fat supports the application of adipose derived PCs as a novel and promising source of cell therapy and regenerative medicine.

Comparison of different uncoated and starch-coated superparamagnetic iron oxide nanoparticles: Implications for stem cell tracking.

However, labelling of stem cells using nanoparticles (NPs) for tracking purpose has been intensively investigated, the biosafety of these materials needs more clarification. Herein, different forms of iron oxide Fe2O3, Fe3O4, and CoxNi1-x Fe2O4 NPs either uncoated or starch-coated (ST-coated) were prepared. We successfully labelled adipose-derived stem cells (ASCs) using these NPs with the aid of lipofectamine as a transfection agent (TA). We then evaluated the effect of these NPs on stem cell proliferation, viability, migration and angiogenesis. Results showed that ASCs labelled with Fe2O3, Fe3O4, ST-Fe2O3 and ST-Fe3O4 did not show any significant difference in proliferation compared to that of TA-treated cells. Moreover, they have shown a protective effect against apoptosis. Conversely, CoxNi1-x Fe2O4 NPs caused a significant decrease in cell proliferation. Compared to that of the TA-treated cells, the migration capacity of cells labelled with Fe2O3, Fe3O4 and CoxNi1-xFe2O4 was significantly compromised. Interestingly, the ST-coated composites reversed this effect. Among the groups treated with different NPs, the angiogenic potential of the ASCs was most robust in the ST-Fe2O3-treated group. In conclusion, labelling ASCs with ST-Fe2O3 NPs enhanced cell migration and angiogenic potential and conferred higher resistance to apoptosis than labelling the cells with the other tested NPs.

Oocyte Aging: The Role of Cellular and Environmental Factors and Impact on Female Fertility.

Female aging is one of the most important factors that impacts human reproduction. With aging, there is a natural decline in female fertility. The decrease in fertility is slow and steady in women aged 30-35 years; however, this decline is accelerated after the age of 35 due to decreases in the ovarian reserve and oocyte quality. Human oocyte aging is affected by different environmental factors, such as dietary habits and lifestyle. The ovarian microenvironment contributes to oocyte aging and longevity. The immediate oocyte microenvironment consists of the surrounding cells. Crosstalk between the oocyte and microenvironment is mediated by direct contact with surrounding cells, the extracellular matrix, and signalling molecules, including hormones, growth factors, and metabolic products. In this review, we highlight the different microenvironmental factors that accelerate human oocyte aging and decrease oocyte function. The ovarian microenvironment and the stress that is induced by environmental pollutants and a poor diet, along with other factors, impact oocyte quality and function and contribute to accelerated oocyte aging and diseases of infertility.

Characterization of embryonic cells obtained from multifetal reduction.

The multifetal reduction (MFR) procedure is usually reserved for high-order multiple pregnancies, and aspirated tissues are typically discarded. In this study, cells obtained from MFR tissue (termed multifetal reduction embryonic cells (MFR-ECs)), were characterized in vitro by genotypic and phenotypic analyses and tested in vivo by injection under the kidney capsule of nude mice. MFR-ECs were highly proliferative in culture and showed a normal karyotype by microarray CGH. Immunohistochemical analysis at day zero showed positive focal staining for desmin, S-100 protein, synaptophysin and chromogranin. Histology examination showed a mixture of cells from the three germ layers at different stages of differentiation. Markers of these stages included important developmental transcription factors, such as beta three-tubulin (ectoderm), paired box 6 (ectoderm) and alpha-smooth muscle actin (mesoderm). Quantitative polymerase chain reaction (qPCR) showed down-regulation of the mRNAs of cancer-related genes such as TP53. In vivo transplantation in nude mice showed a typical hyaline cartilage plate and no teratoma formation. Thus, MFR-ECs represent a rich, unique source for studying stem cell development, embryogenesis and cell differentiation.

Telomerase reverse transcriptase coordinates with the epithelial-to-mesenchymal transition through a feedback loop to define properties of breast cancer stem cells.

Telomerase and its core component, telomerase reverse transcriptase (hTERT), are critical for stem cell compartment integrity. Normal adult stem cells have the longest telomeres in a given tissue, a property mediated by high hTERT expression and high telomerase enzymatic activity. In contrast, cancer stem cells (CSCs) have short telomeres despite high expression of hTERT, indicating that the role of hTERT in CSCs is not limited to telomere elongation and/or maintenance. The function of hTERT in CSCs remains poorly understood. Here, we knocked down hTERT expression in CSCs and observed a morphological shift to a more epithelial phenotype, suggesting a role for hTERT in the epithelial-to-mesenchymal transition (EMT) of CSCs. Therefore, in this study, we systematically explored the relationship between hTERT and EMT and identified a reciprocal, bi-directional feedback loop between hTERT and EMT in CSCs. We found that hTERT expression is mutually exclusive to the mesenchymal phenotype and that, reciprocally, loss of the mesenchymal phenotype represses hTERT expression. We also showed that hTERT plays a critical role in the expression of key CSC markers and nuclear ß-catenin localization, increases the percentage of cells with side-population properties, and upregulates the CD133 expression. hTERT also promotes chemoresistance properties, tumorsphere formation and other important functional CSC properties. Subsequently, hTERT knockdown leads to the loss of the above advantages, indicating a loss of CSC properties. Our findings suggest that targeting hTERT might improve CSCs elimination by transitioning them from the aggressive mesenchymal state to a more steady epithelial state, thereby preventing cancer progression.

Pericytes: The Role of Multipotent Stem Cells in Vascular Maintenance and Regenerative Medicine.

Blood vessels consist of an inner endothelial cell layer lining the vessel wall and perivascular pericytes, also known as mural cells, which envelop the vascular tube surface. Pericytes have recently been recognized for their central role in blood vessel formation. Pericytes are multipotent cells that are heterogeneous in their origin, function, morphology and surface markers. Similar to other types of stem cells, pericytes act as a repair system in response to injury by maintaining the structural integrity of blood vessels. Several studies have shown that blood vessels lacking pericytes become hyperdilated and haemorrhagic, leading to vascular complications ranging from diabetic retinopathy to embryonic death. The role of pericytes is not restricted to the formation and development of the vasculature: they have been shown to possess stem cell-like characteristics and may differentiate into cell types from different lineages. Recent discoveries regarding the contribution of pericytes to tumour metastasis and the maintenance of tumour vascular supply and angiogenesis have led researchers to propose targeting pericytes with anti-angiogenic therapies. In this review, we will examine the different physiological roles of pericytes, their differentiation potential, and how they interact with surrounding cells to ensure the integrity of blood vessel formation and maintenance.

Efficacy of low-dose intratympanic dexamethasone for sudden hearing loss.

OBJECTIVE: Intratympanic steroids (ITSs) are recommended for treatment of sudden sensorineural hearing loss (SSNHL). On the other hand, the dosage, frequency and duration of the intratympanic therapy are still not clear. We aimed to evaluate the efficacy of low-dose intratympanic steroid (ITS) treatment of SSNHL. METHODS: Seventy patients (ears) treated for SSNHL were involved in the study. The patients were divided into four groups: the systemic steroid, combined, intratympanic initial (ITSi) and intratympanic salvage (ITSs). The demographic data, accompanying symptoms, treatment onset duration, the treatment protocol, and pre- and post-treatment pure tone audiometry results were recorded. RESULTS: The mean treatment onset was 60 days in the ITSs group, which is statistically later than the other groups (p<0.001). The treatment response was assessed based on Siegel's criteria. Hearing recovery was statistically higher in the combined group than the systemic steroid group (p=0.042). 87.5% of the ITSi group showed full recovery, which is a statistically significantly higher difference than the other groups (p<0.001). In the salvage treatment group, the use of low-dose ITS was observed to be inadequate for the treatment (p<0.001). The post-treatment pure tone average gains in dB were analyzed at 500, 1000, 2000, and 4000Hz and the recovery determined for each of the four groups was found to be statistically significant (p<0.001 to p<0.031). CONCLUSION: The ITS administration as the initial treatment for mild to moderate hearing loss is adequate while low dose of dexamethasone used as a salvage treatment is inadequate. The use of low-dose ITS in the combined treatment may increase the hearing gain.

Waste biomass-to-energy supply chain management: a critical synthesis.

The development of renewable energy sources has clearly emerged as a promising policy towards enhancing the fragile global energy system with its limited fossil fuel resources, as well as for reducing the related environmental problems. In this context, waste biomass utilization has emerged as a viable alternative for energy production, encompassing a wide range of potential thermochemical, physicochemical and bio-chemical processes. Two significant bottlenecks that hinder the increased biomass utilization for energy production are the cost and complexity of its logistics operations. In this manuscript, we present a critical synthesis of the relative state-of-the-art literature as this applies to all stakeholders involved in the design and management of waste biomass supply chains (WBSCs). We begin by presenting the generic system components and then the unique characteristics of WBSCs that differentiate them from traditional supply chains. We proceed by discussing state-of-the-art energy conversion technologies along with the resulting classification of all relevant literature. We then recognize the natural hierarchy of the decision-making process for the design and planning of WBSCs and provide a taxonomy of all research efforts as these are mapped on the relevant strategic, tactical and operational levels of the hierarchy. Our critical synthesis demonstrates that biomass-to-energy production is a rapidly evolving research field focusing mainly on biomass-to-energy production technologies. However, very few studies address the critical supply chain management issues, and the ones that do that, focus mainly on (i) the assessment of the potential biomass and (ii) the allocation of biomass collection sites and energy production facilities. Our analysis further allows for the identification of gaps and overlaps in the existing literature, as well as of critical future research areas.