Identification of microRNAs and messenger RNAs involved in human umbilical cord mesenchymal stem cell treatment of ischemic cerebral infarction using integrated bioinformatics analysis

In recent years,a large number of differentially expressed genes have been identified in human umbilical cord mesenchymal stem cell(hUMSC)transplants for the treatment of ischemic cerebral infarction.These genes are involved in various biochemical processes,but the role of microRNAs(miRNAs)in this process is still unclear.From the Gene Expression Omnibus(GEO)database,we downloaded two microarray datasets for GSE78731(messenger RNA(mRNA)profile)and GSE97532(miRNA profile).The differentially expressed genes screened were compared between the hUMSC group and the middle cerebral artery occlusion group.Gene ontology enrichment and pathway enrichment analyses were subsequently conducted using the online Database for Annotation,Visualization,and Integrated Discovery.Identified genes were applied to perform weighted gene co-suppression analyses,to establish a weighted co-expression network model.Furthermore,the protein-protein interaction network for differentially expressed genes from turquoise modules was built using Cytoscape(version 3.40)and the most highly correlated subnetwork was extracted from the protein-protein interaction network using the MCODE plugin.The predicted target genes for differentially expressed miRNAs were also identified using the online database starBase v3.0.A total of 3698 differentially expressed genes were identified.Gene ontology analysis demonstrated that differentially expressed genes that are related to hUMSC treatment of ischemic cerebral infarction are involved in endocytosis and inflammatory responses.We identified 12 differentially expressed miRNAs in middle cerebral artery occlusion rats after hUMSC treatment,and these differentially expressed miRNAs were mainly involved in signaling in inflammatory pathways,such as in the regulation of neutrophil migration.In conclusion,we have identified a number of differentially expressed genes and differentially expressed mRNAs,miRNA-mRNAs,and signaling pathways involved in the hUMSC treatment of ischemic cerebral infarction.Bioinformatics and interaction analyses can provide novel clues for further research into hUMSC treatment of ischemic cerebral infarction.

Performance of a Horizontal Flow Constructed Reed Bed Filter for Municipal Wastewater Treatment: The Case Study of the Prototype Installed at Gaston Berger University, Saint-Louis, Senegal

In Saint-Louis, Senegal, a constructed wetland with horizontal flow reed beds (FHa and FHb) has demonstrated significant efficacy in treating municipal wastewater. Analyzing various treatment stages, the system showed only a slight temperature variation, from an influent average of 26.3°C to an effluent of 24.7°C. Electrical conductivity decreased from 1331 mS/cm to 974.5 mS/cm post-primary treatment, with suspended solids (SS) dramatically reduced from 718.9 mg/L to 5.7 mg/L in the final effluent. Biochemical oxygen demand (BOD5) and chemical oxygen demand (COD) saw a notable decrease, from initial levels of 655.6 mg/L and 1240 mg/L to 2.3 mg/L and 71.3 mg/L, respectively. Nitrogenous compounds (N-TN) and phosphates () also decreased significantly, indicating the system’s nutrient removal capacity. Microbiological analysis revealed a reduction in fecal coliforms from 7.5 Ulog/100ml to 1.8 Ulog/100ml and a complete elimination of helminth eggs. The presence of Phragmites and Typha was instrumental in enhancing these reductions. The system’s compliance with the Senegalese standards for disposal into natural environments, WHO recommendations for unrestricted water reuse in irrigation, and the European legislation for water reuse was established. The effluent quality met the stringent criteria for various classes of agricultural reuse, illustrating the system’s potential for sustainable water management. This wetland model presents a robust solution for water-stressed regions, ensuring environmental protection while supporting agricultural needs. The study calls for ongoing research to further refine the system for optimal, reliable wastewater treatment and water resource sustainability.

Development and Validation of a Method for Simultaneous Determination of Metformin Hydrochloride and Sitagliptin Phosphate in a Formulation by RP-HPLC

Present study was aimed to develop and validate a reverse-phase high-performance liquid chromatography method for simultaneous determination of sitagliptin phosphate and metformin hy-drochloride in a marketed formulation. The drug separation was performed on Hibar-240, Li-chrosphere-100 C18 ODS (250 × 4.6 mm, 5 μm) column, at a flow rate of 1 mL/min. The mobile phase used was a mixture of methanol: potassium di-hydrogen phosphate buffer at a ratio of 70:30 v/v. The detection was carried out at a wavelength of 266 nm. The retention times of sitagliptin phosphate and metformin hydrochloride were found as 6.1 and 4.9 min respectively. Linear calibration curves with good correlation coefficients were obtained over the concentration ranges of 10 - 50 μg/mL for sitagliptin and 20 - 100 μg/mL for metformin. The limit of detection was 0.016 and 0.14 μg/mL and the limit of quantification was 0.048 and 0.42 μg/mL for sitagliptin phosphate and metformin hydrochloride respectively. Validation of the method demonstrated system selectivity, specificity, linearity, accuracy and precision. The developed method was found useful in the simultaneous analysis of sitagliptin phosphate and metformin hydrochloride in formulation.

Inorganic phosphate in the development and treatment of cancer:A Janus Bifrons?

Inorganic phosphate(Pi) is an essential nutrient to living organisms. It is required as a component of the energy metabolism,kinase/phosphatase signaling and in the formation and function of lipids,carbohydrates and nucleic acids and,at systemic level,it plays a key role for normal skeletal and dentin mineralization. Pi represents an abundant dietary element and its intestinal absorption is efficient,minimally regulated and typically extends to approximately 70%. Maintenance of proper Pi homeostasis is a critical event and serum Pi level is maintained within a narrow range through an elaborate network of humoral interactions and feedback loops involving intestine,kidney,parathyroid gland and bone,and depends on the activity of a number of hormones,including parathyroid hormone,1,25-dihydroxy vitamin D,and fibroblast growth factor 23 as major regulators of Pi homeostasis. Notably,Pi intake seemingly continues to increase as a consequence of chronic high-phosphorus(P) diets deriving from the growing consumption of highly processed foods,especially restaurant meals,fast foods,and convenience foods. Several recent reports have generated significant associations between high-P intake or high-serum Pi concentration and morbidity and mortality. Many chronic diseases,including cardiovascular diseases,obesity and even cancer have been proposed to be associated with high-P intakes and high-serum Pi concentrations. On the other hand,there is also evidence that Pi can have antiproliferative effects on some cancer cell types,depending on cell status and genetic background and achieve additive cytotoxic effects when combined with doxorubicin,illustrating its potential for clinical applications and suggesting that up-regulating Pi levels at local sites for brief times,might contribute to the development of novel and cheap modalities for therapeutic intervention in some tumours. Overall,the influence of Pi on cell function and the possible relationship to cancer have to be fully understood and investigated further.

Glial Cell-Targeted Treatments for Bipolar Disorder: A Systematic Review of Available Data and Clinical Perspectives

This paper is a systematic review of the treatment of bipolar disorder: a systematic Google Scholar search aimed at treatment guidelines and clinical trials. The search for treatment guidelines returned 375 papers and was last performed from June 1, 2022 to August 30, 2022. The literature suggests that lithium helps control and alleviate severe mood episodes, and olanzapine is effective for acute manic or mixed episodes of bipolar I disorder. Achieving effectiveness or remission is better with Cariprazine. Lurasidone improves cognitive performance. Quetiapine improves sleep quality and co-morbid anxiety. Lamotrigine helps delay depression, mania, and mild manic episodes. Antidepressants are best used in conjunction with mood stabilizers. For co-morbid treatment, carbamazepine and lithium in combination are more effective in the treatment of psychotic mania. Co-morbid anxiety treatment considers adjunctive olanzapine or lamotrigine. Co-morbid bulimia treatment considers a mood stabilizer. Co-morbid fatigue treatment considers a dawn simulator. For diet, pay attention to a healthy diet, patients can ingest probiotics and pay attention to the balance of fatty acids.

Subtotal colonic bypass plus colostomy with antiperistaltic cecoproctostomy for the treatment of slow transit constipation in an aged population:A retrospective control study

AIM To compare the efficacy,improved quality of life,and prognosis in patients undergoing either subtotal colonic bypass with antiperistaltic cecoproctostomy(SCBAC) or subtotal colonic bypass plus colostomy with antiperistaltic cecoproctostomy(SCBCAC) for the treatment of slow transit constipation.METHODS Between October 2010 and October 2014,aged patients with slow transit constipation who were hospitalized and underwent laparoscopic surgery in our institute weredivided into two groups: the bypass group,15 patients underwent SCBAC,and the bypass plus colostomy group,14 patients underwent SCBCAC. The following preoperative and postoperative clinical data were collected: gender,age,body mass index,operative time,first flatus time,length of hospital stay,bowel movements(BMs),Wexner fecal incontinence scale,Wexner constipation scale(WCS),gastrointestinal quality of life index(GIQLI),numerical rating scale for pain intensity(NRS),abdominal bloating score(ABS),and ClavienDindo classification of surgical complications(CD) before surgery and at 3,6,12,and 24 mo after surgery.RESULTS All patients successfully underwent laparoscopic surgery without open surgery conversion or surgeryrelated death. The operative time and blood loss were significantly less in the bypass group than in the bypass plus colostomy group(P = 0.007). No significant differences were observed in first flatus time,length of hospital stay,or complications with CD > 1 between the two groups. No patients had fecal incontinence after surgery. At 3,6,and 12 mo after surgery,the number of BMs was significantly less in the bypass plus colostomy group than in the bypass group. The parameters at 3,6,12,and 24 mo after surgery in both groups significantly improved compared with the preoperative conditions(P < 0.05),except NRS at 3,6 mo after surgery in both groups,ABS at 12,24 mo after surgery and NRS at 12,24 mo after surgery in the bypass group. WCS,GIQLI,NRS,and ABS significantly improved in the bypass plus colostomy group compared with the bypass group at 3,6,12,and 24 mo after surgery(P < 0.05) except WCS,NRS at 3,6 mo after surgery and ABS at 3 mo after surgery. At 1 year after surgery,a barium enema examination showed that the emptying time was significantly better in the bypass plus colostomy group than in the bypass group(P = 0.007).CONCLUSION Laparoscopic SCBCAC is an effective and safe procedure for the treatment of slow transit constipation in an aged population and can significantly improve the prognosis. Its clinical efficacy is more favorable compared with that of SCBAC. Laparoscopic SCBCAC is a better procedure for the treatment of slow transit constipation in an aged population.

Pathogenesis, diagnosis, and treatment of epilepsy: electromagnetic stimulation-mediated neuromodulation therapy and new technologies

Epilepsy is a severe,relapsing,and multifactorial neurological disorder.Studies regarding the accurate diagnosis,prognosis,and in-depth pathogenesis are crucial for the precise and effective treatment of epilepsy.The pathogenesis of epilepsy is complex and involves alterations in variables such as gene expression,protein expression,ion channel activity,energy metabolites,and gut microbiota composition.Satisfactory results are lacking for conventional treatments for epilepsy.Surgical resection of lesions,drug therapy,and non-drug interventions are mainly used in clinical practice to treat pain associated with epilepsy.Non-pharmacological treatments,such as a ketogenic diet,gene therapy for nerve regeneration,and neural regulation,are currently areas of research focus.This review provides a comprehensive overview of the pathogenesis,diagnostic methods,and treatments of epilepsy.It also elaborates on the theoretical basis,treatment modes,and effects of invasive nerve stimulation in neurotherapy,including percutaneous vagus nerve stimulation,deep brain electrical stimulation,repetitive nerve electrical stimulation,in addition to non-invasive transcranial magnetic stimulation and transcranial direct current stimulation.Numerous studies have shown that electromagnetic stimulation-mediated neuromodulation therapy can markedly improve neurological function and reduce the frequency of epileptic seizures.Additionally,many new technologies for the diagnosis and treatment of epilepsy are being explored.However,current research is mainly focused on analyzing patients’clinical manifestations and exploring relevant diagnostic and treatment methods to study the pathogenesis at a molecular level,which has led to a lack of consensus regarding the mechanisms related to the disease.

Overview of Research on the Clinical Treatment of Allergic Rhinitis

Three kinds of treatment for allergic rhinitis(Western medicine,traditional Chinese medicine and their combination)were described respectively,and the different treatment methods of AR and their characteristics were analyzed.This study will help to further improve the diagnosis and treatment of the disease and promote the early recovery of patients.

Epidemiological and clinical features,treatment status,and economic burden of traumatic spinal cord injury in China:a hospital-based retrospective study

Traumatic spinal cord injury is potentially catastrophic and can lead to permanent disability or even death.China has the largest population of patients with traumatic spinal cord injury.Previous studies of traumatic spinal cord injury in China have mostly been regional in scope;national-level studies have been rare.To the best of our knowledge,no national-level study of treatment status and economic burden has been performed.This retrospective study aimed to examine the epidemiological and clinical features,treatment status,and economic burden of traumatic spinal cord injury in China at the national level.We included 13,465 traumatic spinal cord injury patients who were injured between January 2013 and December 2018 and treated in 30 hospitals in 11 provinces/municipalities representing all geographical divisions of China.Patient epidemiological and clinical features,treatment status,and total and daily costs were recorded.Trends in the percentage of traumatic spinal cord injuries among all hospitalized patients and among patients hospitalized in the orthopedic department and cost of care were assessed by annual percentage change using the Joinpoint Regression Program.The percentage of traumatic spinal cord injuries among all hospitalized patients and among patients hospitalized in the orthopedic department did not significantly change overall(annual percentage change,-0.5%and 2.1%,respectively).A total of 10,053(74.7%)patients underwent surgery.Only 2.8%of patients who underwent surgery did so within 24 hours of injury.A total of 2005(14.9%)patients were treated with high-dose(≥500 mg)methylprednisolone sodium succinate/methylprednisolone(MPSS/MP);615(4.6%)received it within 8 hours.The total cost for acute traumatic spinal cord injury decreased over the study period(-4.7%),while daily cost did not significantly change(1.0%increase).Our findings indicate that public health initiatives should aim at improving hospitals’ability to complete early surgery within 24 hours,which is associated with improved sensorimotor recovery,increasing the awareness rate of clinical guidelines related to high-dose MPSS/MP to reduce the use of the treatment with insufficient evidence.

Targeted therapy or immunotherapy? Optimal treatment in hepatocellular carcinoma

Hepatocellular carcinoma(HCC) is the fifth leading cause of cancer mortality in the United States and the second leading cause of cancer mortality worldwide. Sorafenib is the only food and drug administration(FDA) approved as first line systemic treatment in HCC. Regorafenib and nivolumab are the only FDA approved second line treatment after progression on sorafenib. We will discuss all potential first and second line options in HCC. In addition, we also will explore sequencing treatment options in HCC, and examine biomarkers that can potentially predict benefits from treatments such as immune checkpoint inhibitor. This minireview summarizes potential treatments in HCC based on clinical trials that have been published in manuscript or abstract format from 1994-2018.

The influence of intestine-based treatment using Xuan Bai Cheng Qi Tang on the concentration of trace elements in the main organs of COPD rats

Objective:To test two theories from traditional Chinese medicine:'exterior -interior relationship between the lung and large intestine' and 'treating from the intestine principle for lung disorders'.The influence of intestine-based treatment using Xuan Bai Cheng Qi Tang (XBCQT) on the concentration of three trace elements-copper (Cu),zinc (Zn),and manganese (Mn)-was observed in the tissues of the lung,small intestine,large intestine,and stomach of rats suffering from chronic obstructive pulmonary disease (COPD).Methods:Thirty-five male Wistar rats were divided randomly and equally into five groups:control;model;Fei treatment (A);Chang treatment (B);and Fei-Chang treatment (C).A rat model of COPD was prepared by tracheal injection of lipopolysaccharide plus exposure to cigarette smoke.Treatments with medicinal herbs started day-22 of administration and exposure to cigarette smoke for 7 days.The control group and model group were administered physiologic (0.9%) saline solution via the stomach.After 7 days of intervention,the tissues of the lung,small intestine,large intestine,and stomach were removed.Inductively coupled plasma-atomic emission spectroscopy was used to detect the levels of Cu,Zn,and Mn in those tissues.Results:Compared with the control group,the Cu concentration in the tissues of the small intestine,large intestine,and stomach increased significantly in the model group (P <.05);the Mn concentration in the tissues of the lung,large intestine,and stomach increased significantly in the model group (P <.05);the Zn concentration in the tissues of the lung and large intestine decreased significantly in the model group (P <.05).In comparison of the model group:the Cu concentration in the tissues of the lung and large intestine decreased significantly in the B group (P <.05);the Mn concentration in the tissues of the lung,small intestine,and large intestine decreased significantly in the B group (P <.05);the Zn concentration in the tissues of the lung,small intestine,and large intestine increased significantly in the B group (P <.05).For the A group versus C group comparison,the Zn concentration in the tissues of the small intestine and stomach increased significantly in the latter (P <.05).Conclusion:This study showed that 'treating from the intestine' using Xuan Bai Cheng Qi Tang and its modified formulae can regulate the concentration of trace elements in the main organs of COPD rats.This may be one of the mechanisms for intestine-based treatment for COPD.

Cardiac autonomic neuropathy: Risk factors, diagnosis and treatment

Cardiac autonomic neuropathy(CAN)is a serious complication of diabetes mellitus(DM)that is strongly associated with approximately five-fold increased risk of cardiovascular mortality.CAN manifests in a spectrum of things,ranging from resting tachycardia and fixed heart rate(HR)to development of"silent"myocardial infarction.Clinical correlates or risk markers for CAN are age,DM duration,glycemic control,hypertension,and dyslipidemia(DLP),development of other microvascular complications.Established risk factors for CAN are poor glycemic control in type 1 DM and a combination of hypertension,DLP,obesity,and unsatisfactory glycemic control in type 2DM.Symptomatic manifestations of CAN include sinus tachycardia,exercise intolerance,orthostatic hypotension(OH),abnormal blood pressure(BP)regulation,dizziness,presyncope and syncope,intraoperative cardiovascular instability,asymptomatic myocardial ischemia and infarction.Methods of CAN assessment in clinical practice include assessment of symptoms and signs,cardiovascular reflex tests based on HR and BP,short-term electrocardiography(ECG),QT interval prolongation,HR variability(24 h,classic24 h Holter ECG),ambulatory BP monitoring,HR turbulence,baroreflex sensitivity,muscle sympathetic nerve activity,catecholamine assessment and cardiovascular sympathetic tests,heart sympathetic imaging.Although it is common complication,the significance of CAN has not been fully appreciated and there are no unified treatment algorithms for today.Treatment is based on early diagnosis,life style changes,optimization of glycemic control and management of cardiovascular risk factors.Pathogenetic treatment of CAN includes:Balanced diet and physical activity;optimization of glycemic control;treatment of DLP;antioxidants,first of allα-lipoic acid(ALA),aldose reductase inhibitors,acetylL-carnitine;vitamins,first of all fat-soluble vitamin B1;correction of vascular endothelial dysfunction;prevention and treatment of thrombosis;in severe cases-treatment of OH.The promising methods include prescription of prostacyclin analogues,thromboxane A2 blockers and drugs that contribute into strengthening and/or normalization of Na^+,K^+-ATPase(phosphodiesterase inhibitor),ALA,dihomo-γ-linolenic acid(DGLA),ω-3 polyunsaturated fatty acids(ω-3 PUFAs),and the simultaneous prescription of ALA,ω-3 PUFAs and DGLA,but the future investigations are needed.Development of OH is associated with severe or advanced CAN and prescription of nonpharmacological and pharmacological,in the foreground midodrine and fludrocortisone acetate,treatment methods are necessary.

Surgical treatment of inflammatory bowel disease:From the gastroenterologist’s stand-point

Treatment of ulcerative colitis(UC)and Crohn’s disease(CD)represents,in the majority of cases,a real challenge to the gastroenterologist’s abilities and skills as well as a clinical test concerning his/her levels of medical knowledge and experience.During the last two decades,our pharmaceutical arsenal was significantly strengthened,especially after the introduction of the so-called biological agents,drugs which to a large extent not only improved the results of conservative treatment but also changed the natural history of the disease.However,colectomy is still necessary for some patients with severe UC although smaller compared to the past,precisely because of the improvements achieved in the available conservative treatment.Nevertheless,surgeries to treat colon dysplasia and cancer are increasing to some extent.At the same time,satisfactory improvements in surgical techniques,the pre-and post-operative care of patients,as well as the selection of the appropriate time for performing the surgery have been noticed.Regarding patients with CD,the improvement of conservative treatment did not significantly change the need for surgical treatment since two-thirds of patients need to undergo surgery at some point in the course of their disease.On the other hand,the outcome of the operation has improved through good preoperative care as well as the wide application of more conservative surgical techniques aimed at keeping as much of the bowel in situ as possible.This article discusses the indications for surgical management of UC patients from the gastroenterologist’s point of view,the results of the emerging new techniques such as transanal surgery and robotics,as well as alternative operations to the classic ileo-anal-pouch anastomosis.The author also discusses the basic principles of surgical management of patients with CD based on the results of the relevant literature.The self-evident is emphasized,that is,to achieve an excellent therapeutic result in patients with severe inflammatory bowel disease in today’s era;the close cooperation of gastroenterologists with surgeons,pathologists,imaging,and nutritionists is of paramount importance.

Prevalence of metabolic syndrome in type 2 diabetic patients: A comparative study using WHO, NCEP ATP III, IDF and Harmonized definitions

To determine the prevalence of metabolic syndrome (MetS) in Malaysian type 2 diabetic patients using WHO, NCEP ATP III, IDF and the new Harmonized definitions, and the concordance between these definitions. This study involved 313 patients diagnosed with type 2 diabetes mellitus (T2DM) at two Malaysian tertiary hospitals. Socio-demographic data were assessed using a pre-tested interviewer-administered structured questionnaire. Anthropometric measurements were carried out according to standard protocols. Clinical and laboratory characteristics were examined. Kappa (k) statistics were used for the agreement between the four MetS definitions. The overall prevalence rates of MetS (95% CI) were 95.8% (93.6-98.1), 96.1% (94.0-98.3), 84.8% (80.8-88.9) and 97.7% (96.1-99.4) according to the WHO, NCEP ATP III, IDF and the Harmonized definitions, respectively. The Kappa statistics demonstrated a slight to substantial agreement between the definitions (k = 0.179-0.875, p k = 0.875, p hest specificity (100%) in identifying MetS. In conclusion, the new Harmonized criteria established the highest prevalence of MetS among the four definitions applied. There was a very good concordance between the WHO and NCEP ATP III criteria. The extremely high prevalence of MetS observed in type 2 diabetic patients indicates an impending pandemic of CVD risk in Malaysia. Aggressive treatment of MetS components is required to reduce cardiovascular risk in T2DM.

Challenges and prospects in bridging precision medicine and artificial intelligence in genomic psychiatric treatment

Precision medicine is transforming psychiatric treatment by tailoring personalized healthcare interventions based on clinical,genetic,environmental,and lifestyle factors to optimize medication management.This study investigates how artificial intelligence(AI)and machine learning(ML)can address key challenges in integrating pharmacogenomics(PGx)into psychiatric care.In this integration,AI analyzes vast genomic datasets to identify genetic markers linked to psychiatric conditions.AI-driven models integrating genomic,clinical,and demographic data demonstrated high accuracy in predicting treatment outcomes for major depressive disorder and bipolar disorder.This study also examines the pressing challenges and provides strategic directions for integrating AI and ML in genomic psychiatry,highlighting the importance of ethical considerations and the need for personalized treatment.Effective implementation of AI-driven clinical decision support systems within electronic health records is crucial for translating PGx into routine psychiatric care.Future research should focus on developing enhanced AI-driven predictive models,privacy-preserving data exchange,and robust informatics systems to optimize patient outcomes and advance precision medicine in psychiatry.

Disposal and Treatment Methods for Pesticide Containing Wastewaters: Critical Review and Comparative Analysis

Pesticides provide the primary means for controlling organisms that compete with man for food and fibre or cause injury to man, livestock and crops. They played a vital role in the economic production of wide ranges of vegetable, fruit, cereal, forage, fibre and oil crops which now constitute a large part of successful agricultural industry in many countries. After application to the target areas, pesticide residues are removed from applicators by rinsing with water which results in the formation of a toxic wastewater that represents a disposal problem for many farmers. Pesticides can adversely affect people, pets, livestock and wildlife in addition to the pests they are intended to destroy. The phenomenon of biomagnification of some pesticides has resulted in reproductive failure of some fish species and egg shell thinning of birds such as peregrine falcons, sparrow hawk and eagle owls. Pesticide toxicity to humans include skin and eye irritation and skin cancer. Therefore, care must be exercised in the application, disposal and treatment of pesticides. Currently, disposal of pesticide wastewater is carried out by: 1) land cultivation, 2) dumping in soil pits, plastic pits and concrete pits or on land and in extreme cases in streams near the rinsing operation, 3) use of evaporation beds and 4) land filling. These methods of disposal are unsafe as the surface run off will reach streams, rivers and lakes and the infiltration of the wastewater into the local soil will eventually reach ground water. The treatment methods currently used for pesticide wastewater include: 1) incineration (incinerators and open burning), 2) chemical treatments (O3/UV, hydrolysis, Fenton oxidation and KPEG), 3) physical treatments (inorganic, organic absorbents and activated carbon) and 4) biological treatments (composting, bioaugmentation and phytoremediation). Therefore, the choice of safe, on farm disposal techniques for agricultural pesticides is very important. A comparative analysis was performed on 18 methods of pesticide disposal/treatment using six criteria: containment, detoxification ability, cost, time, suitability for on farm use, size and evaporation efficiency. The results indicated that of the 18 methods evaluated, 9 scored above 80/100 and can be used on farm. They were organic absorbents (97), composting (94), bioaugmentation (92), inorganic absorbents (90), Fenton oxidation (86), O3/UV (83), activated carbon (82), hydrolysis (82), and land cultivation (80). The other methods are not suitable for on farm use as they suffered from containment problems, high cost and variability of effectiveness.

Redox, immune and genetic biomarker system for personalized treatments in colorectal cancer

BACKGROUND Identifying biomarkers for the risk of developing degenerative processes linked to aging and colorectal cancer(CRC) onset that could improve clinical strategies.AIM To determine valid targets and a predictive biomarker's system of chronicization of inflammation for cancer treatment.METHODS A group of 147 CRC patients was studied. Clinical diagnosis was confirmed histopathologically, and patients were sub-typed using the pathological tumornode-metastasis classification. Thirteen colon adenoma patients and 219 healthy subjects were also studied. A system biology study on Thioredoxin1/CD30 redox-immune systems(Trx1/CD30), T helper cytokines and polymorphisms of killer immunoglobulin-like receptors, FcγRIIa-131 H/R and FcγRIIIa-158 V/F was carried out. Enzyme-linked immunosorbent assay was performed to analyze sera.Genetic study was executed by polymerase chain reaction sequence-specific primers and sequence-based typing method. Statistical analysis was performed by using the "Statgraphics software systems".RESULTS We found a positive increase between Trx1/RTrx1 levels and sCD30 level and increased age. With respect to the gender relationships, there were distinct differences. Females showed a primary relationship between transforming growth factor beta(TGFβ) with Trx1, whereas males had one with TGFβ and RTrx1. Trx1/CD30 controls the redox immune homeostasis, and an imbalance in the relationship between the Trx1/RTrx1 and sCD30 levels is linked to the onset and progression of tumor. This event happens through different gender-specific cytokine pathways. Our study demonstrated that the serum levels ofTrx1/RTrx1, TGFβ/interleukin(IL)6 and TGFβ/IL4 combinations and the sCD30,IFNγ and IL2 combination constitute a predictive gender specific biomarker system. This is relevant for clinical screening to detect the risk of the potential development or progression of a tumor.CONCLUSION Oxidative stress on Trx1/CD30 is a trigger of cancer disease, and the selected oxidation and immune products are a biomarker system for aging and cancer.

Endoscopic and surgical resection of T1a/T1b esophageal neoplasms: A systematic review

AIM: To investigate potential therapeutic recommendations for endoscopic and surgical resection of T1a/ T1b esophageal neoplasms. METHODS: A thorough search of electronic databases MEDLINE, Embase, Pubmed and Cochrane Library, from 1997 up to January 2011 was performed. An analysis was carried out, pooling the effects of outcomes of 4241 patients enrolled in 80 retrospective studies. For comparisons across studies, each reporting on only one endoscopic method, we used a random effects meta-regression of the log-odds of the outcome of treatment in each study. "Neural networks" as a data mining technique was employed in order to establish a prediction model of lymph node status in superficial submucosal esophageal carcinoma. Another data mining technique, the "feature selection and root cause analysis", was used to identify the most impor-tant predictors of local recurrence and metachronous cancer development in endoscopically resected patients, and lymph node positivity in squamous carcinoma (SCC) and adenocarcinoma (ADC) separately in surgically resected patients. RESULTS: Endoscopically resected patients: Low grade dysplasia was observed in 4% of patients, high grade dysplasia in 14.6%, carcinoma in situ in 19%, mucosal cancer in 54%, and submucosal cancer in 16% of patients. There were no significant differences between endoscopic mucosal resection and endoscopic submucosal dissection (ESD) for the following parameters: complications, patients submitted to surgery, positive margins, lymph node positivity, local recurrence and metachronous cancer. With regard to piecemeal resection, ESD performed better since the number of cases was significantly less [coefficient: -7.709438, 95%CI: (-11.03803, -4.380844), P < 0.001]; hence local recurrence rates were significantly lower [coefficient: -4.033528, 95%CI: (-6.151498, -1.915559),P < 0.01]. A higher rate of esophageal stenosis was observed following ESD [coefficient: 7.322266, 95%CI: (3.810146, 10.83439), P < 0.001]. A significantly greater number of SCC patients were submitted to surgery (log-odds, ADC: -2.1206 ± 0.6249 vs SCC: 4.1356 ± 0.4038, P < 0.05). The odds for re-classification of tumor stage after endoscopic resection were 53% and 39% for ADC and SCC, respectively. Local tumor recurrence was best predicted by grade 3 differentiation and piecemeal resection, metachronous cancer development by the carcinoma in situ component, and lymph node positivity by lymphovascular invasion. With regard to surgically resected patients: Significant differences in patients with positive lymph nodes were observed between ADC and SCC [coefficient: 1.889569, 95%CI: (0.3945146, 3.384624), P<0.01). In contrast, lymphovascular and microvascular invasion and grade 3 patients between histologic types were comparable, the respective rank order of the predictors of lymph node positivity was: Grade 3, lymphovascular invasion (L+), microvascular invasion (V+), submucosal (Sm) 3 invasion, Sm2 invasion and Sm1 invasion. Histologic type (ADC/SCC) was not included in the model. The best predictors for SCC lymph node positivity were Sm3 invasion and (V+). For ADC, the most important predictor was (L+). CONCLUSION: Local tumor recurrence is predicted by grade 3, metachronous cancer by the carcinoma insitu component, and lymph node positivity by L+. T1b cancer should be treated with surgical resection.

Involvement of blood mononuclear cells in the infertility, age-associated diseases and cancer treatment

Blood mononuclear cells consist of T cells and monocyte derived cells. Beside immunity, the blood mononuclear cells belong to the complex tissue control system(TCS), where they exhibit morphostatic function by stimulatingproliferation of tissue stem cells followed by cellular differentiation, that is stopped after attaining the proper functional stage, which differs among various tissue types. Therefore, the term immune and morphostatic system(IMS) should be implied. The TCS-mediated morphostasis also consists of vascular pericytes controlled by autonomic innervation, which is regulating the quantity of distinct tissues in vivo. Lack of proper differentiation of tissue cells by TCS causes either tissue underdevelopment, e.g., muscular dystrophy, or degenerative functional failures, e.g., type 1 diabetes and age-associated diseases. With the gradual IMS regression after 35 years of age the gonadal infertility develops, followed by a growing incidence of age-associated diseases and cancers. Without restoring an altered TCS function in a degenerative disease, the implantation of tissue-specific stem cells alone by regenerative medicine can not be successful. Transfused young blood could temporarily restore fertility to enable parenthood. The young blood could also temporarily alleviate aging diseases, and this can be extended by substances inducing IMS regeneration, like the honey bee propolis. The local and/or systemic use of honey bee propolis stopped hair and teeth loss, regressed varicose veins, improved altered hearing, and lowered high blood pressure and sugar levels. Complete regression of stage Ⅳ ovarian cancer with liver metastases after a simple elaborated immunotherapy is also reported.

Pharmacologic approaches to treatment resistant depression:Evidences and personal experience

AIM: To review evidence supporting pharmacological treatments for treatment-resistant depression(TRD) and to discuss them according to personal clinical experience.METHODS: Original studies, clinical trials, systematic reviews, and meta-analyses addressing pharmacological treatment for TRD in adult patients published from 1990 to 2013 were identified by data base queries(Pub Med, Google Scholar e Quertle Searches) using terms: "treatment resistant depression", "treatment refractory depression", "partial response depression", "non responder depression", "optimization strategy", "switching strategy", "combination strategy", "augmentation strategy", selective serotonin reuptake inhibitors antidepressants(SSRI), tricyclic antidepressants(TCA), serotonin norepinephrine reuptake inhibitors antidepressants, mirtazapine, mianserine, bupropione, monoamine oxidase inhibitor antidepressant(MAOI), lithium, thyroid hormones, second generation antipsychotics(SGA), dopamine agonists, lamotrigine, psychostimulants, dextromethorphan, dextrorphan, ketamine, omega-3 fatty acids, S-adenosil-L-metionine, methylfolat, pindolol, sex steroids, glucocorticoid agents. Other citations of interest were further identified from references reported in the accessed articles. Selected publications were grouped by treatment strategy:(1) switching from an ineffective antidepressant(AD) to a new AD from a similar or different class;(2) combining the current AD regimen with a second AD from a different class; and(3) augmenting the current AD regimen with a second agent not thought to be an antidepressant itself.RESULTS: Switching from a TCA to another TCA provides only a modest advantage(response rate 9%-27%), while switching from a SSRI to another SSRI is more advantageous(response rate up to 75%). Evidence supports the usefulness of switching from SSRI to venlafaxine(5 positive trials out 6), TCA(2 positive trials out 3), and MAOI(2 positive trials out 2) but not from SSRI to bupropione, duloxetine and mirtazapine. Three reviews demonstrated that the benefits of intraand cross-class switch do not significantly differ. Data on combination strategy are controversial regarding TCA-SSRI combination(positive results in old studies, negative in more recent study) and bupropion-SSRI combination(three open series studies but not three controlled trails support the useful of this combination) and positive regard mirtazapine(or its analogue mianserine) combination with ADs of different classes. As regards the augmentation strategy, available evidences supported the efficacy of TCA augmentation with lithium salts and thyroid hormone(T3), but are conflicting regard the SSRI augmentation with these two drugs(1 positive trial out of 4 for lithium and 3 out of 5 for thyroid hormone). Double-blind controlled studies showed the efficacy of AD augmentation with aripiprazole(5 positive trials out 5), quetiapine(3 positive trials out 3) and, at less extent, of fluoxetine augmentation with olanzapine(3 positive trials out 6), so these drugs received the FDA indication for the acute treatment of TRD. Results on AD augmentation with risperidone are conflicting(2 short term positive trials, 1 short-term and 1 long-term negative trials). Case series and open-label trials showed that AD augmentation with pramipexole or ropinirole, two dopamine agonists, could be an effective treatment for TRD(response rate to pramipexole 48%-74%, to ropinirole 40%-44%) although one recent double-blind placebo-controlled study does not support the superiority of pramipexole over placebo. Evidences do not justify the use of psychostimulants, omega-3 fatty acids, S-adenosil-Lmetionine, methylfolate, pindolol, lamotrigine, and sex hormone as AD augmentation for TRD. Combining the available evidences with our experience we suggest treating non-responders to one SSRI bupropion or mirtazapine trial by switching to venlafaxine, and nonresponders to one venlafaxine trial by switching to a TCA or, if TCA are not tolerated, combining mirtazapine with SSRI or venlafaxine. In non-responders to two or more ADs(including at least one TCA if tolerated) current AD regimen could be augmented with lithium salts(mainly in patients with bipolar depression or suicidality), SGAs(mostly aripiprazole) or DA-agonists(mostly pramipexole). In patients with severe TRD, i.e., non-responders to combination and augmentation strategies as well as to electroconvulsive therapy if workable, we suggest to try a combination plus augmentation strategy.CONCLUSION: Our study identifies alternative effective treatment strategies for TRD. Further studies are needed to compare the efficacy of different strategies in more homogeneous subpopulations.