Genetic investigation of 93 families with microphthalmia or posterior microphthalmos.

Microphthalmia is a developmental eye defect that is highly variable in severity and in its potential for systemic association. Despite the discovery of many disease genes in microphthalmia, at least 50% of patients remain undiagnosed genetically. Here, we describe a cohort of 147 patients (93 families) from our highly consanguineous population with various forms of microphthalmia (including the distinct entity of posterior microphthalmos) that were investigated using a next-generation sequencing multi-gene panel (i-panel) as well as whole exome sequencing and molecular karyotyping. A potentially causal mutation was identified in the majority of the cohort with microphthalmia (61%) and posterior microphthalmos (82%). The identified mutations (55 point mutations, 15 of which are novel) spanned 24 known disease genes, some of which have not or only very rarely been linked to microphthalmia (PAX6, SLC18A2, DSC3 and CNKSR1). Our study has also identified interesting candidate variants in 2 genes that have not been linked to human diseases (MYO10 and ZNF219), which we present here as novel candidates for microphthalmia. In addition to revealing novel phenotypic aspects of microphthalmia, this study expands its allelic and locus heterogeneity and highlights the need for expanded testing of patients with this condition.

Describing and expanding the clinical phenotype of anti-MDA5-associated rapidly progressive interstitial lung disease: case series of nine Canadian patients and literature review.

OBJECTIVE: To describe and expand the phenotype of anti-MDA5-associated rapidly progressive interstitial lung disease (MDA5-RPILD) in Canadian patients. METHOD: All proven cases of MDA5-RPILD hospitalized in the University of Montreal's affiliated centres from 2004 to 2015 were selected for inclusion. RESULTS: Of nine consecutive patients, RPILD was the presenting manifestation in seven, whereas two patients developed RPILD 2 years after the onset of arthritis and of chronic interstitial lung disease. In the case with arthritis, RPILD was probably triggered by initiation of tumour necrosis factor-α-inhibitor therapy. In most patients (89%), RPILD was accompanied by concomitant onset of palmar/lateral finger papules, skin ulcerations, and/or mechanic's hands. All patients experienced profound weight loss over 1-2 months (mean ± SD 10.2 ± 4.8 kg). All had arthralgias and/or arthritis. Six patients were clinically amyopathic; only one patient had creatine kinase (CK) levels > 500 U/L. Initial ferritin and transaminase levels were elevated in 86% and 67% of patients, respectively. The antinuclear antibody (ANA) test was negative for nuclear and cytoplasmic staining; antisynthetase autoantibodies were negative. Three patients died; time from initial symptoms to death ranged from 7 to 15 weeks. All six survivors received mycophenolate mofetil and/or tacrolimus as part of induction and/or maintenance therapy. CONCLUSION: In an inpatient setting, RPILD associated with characteristic skin rashes, profound weight loss, articular symptoms, normal or low CK with elevated ferritin, and absent fluorescence on ANA testing should alert the clinician to the possibility of MDA5-RPILD. T-cell-mediated therapies may play a role in this highly lethal condition.

Men's perceptions of and participation in family planning in Aqaba and Ma'an governorates, Jordan.

Men's participation in family planning has become a cornerstone in women's reproductive health. The aim of this study was to examine knowledge, attitudes and practice towards family planning of Jordanian men in southern Jordan. In a cross-sectional descriptive study in 2012, structured interviews were made with 104 married men in Aqaba and Ma'an governorates. Although 93.5% of the men had heard about family planning-most commonly the intrauterine device (IUD) and oral contraceptives-only 45.1% reported that they and their wife currently used it. Most men agreed about a minimum 2 years' child spacing (93.3%) and starting contraception after childbirth (71.2%) and that husband and wife should share decisions about family planning (90.2%) and the number of children (89.5%). Level of education significantly affected current use of contraception, while number of children significantly affected previous use of contraception. Although married men had positive attitudes and good knowledge about family planning, this did not translate into practice of contraceptive use.

Thymol and carvacrol prevent cisplatin-induced nephrotoxicity by abrogation of oxidative stress, inflammation, and apoptosis in rats.

The aim of the present study is to assess the possible protective effects of thymol and carvacrol against cisplatin (CP)-induced nephrotoxicity. A single dose of CP {6 mg/kg, intraperitoneally (i.p.)} injected to male rats revealed significant increases in serum urea, creatinine, and tumor necrosis factor alpha levels. It also increased kidney contents of malondialdehyde and caspase-3 activity with significant reduction in serum albumin, kidney content of reduced glutathione as well as catalase, and superoxide dismutase activity as compared to that of the control group. In contrast, administration of thymol {20 mg/kg, orally (p.o.)} and/or carvacrol (15 mg/kg, p.o.) for 14 days before CP injection and for 7 days after CP administration restored the kidney function and examined oxidative stress parameters. In conclusion, thymol was more effective nephroprotective than carvacrol. Moreover, a combination of thymol and carvacrol had a synergistic nephroprotective effect that might be attributed to antioxidant, anti-inflammatory, and antiapoptotic activities.

Exploring nanoarchitectonics and optical properties of PAA-ZnO@BCP wide-band-gap organic semiconductors.

This work reports the formation of polyacrylic acid (PAA)-zinc oxide (ZnO)-bromocresol purple (BCP), (PAA-ZnO@ (0.00-0.01) BCP wide-bandgap organic semiconductors deposited onto glass substrates via a sol-gel polymerization process. These semiconductor films were deposited on glass substrates using a spin coating and then dried at 60 °C. The PAA-ZnO film appeared to be of amorphous phase, and films loaded with BCP revealed semicrystalline behavior. The surface of the films exhibited adherence and extended grains. The hydrogen bonds formed between PAA-ZnO and the BCP dye within the PAA-ZnO@BCP films was performed using FTIR-spectroscopy. The prepared nanocomposites demonstrate an indirect band transition which is affected slightly by adding ZnO and BCP dye. Optical parameters such as the absorption coefficient, the refractive index, the dielectric constant, optical conductivity, optical depth, and optical electronegativity of the prepared nanocomposites were studied as functions of incident light energy (wavelength). The PAA carbonyl group n-π* transition and BCP aromatic ring π-π* transitions were detected at about 285 (for all samples) and 432 nm (for BCP loaded samples), respectively. The superior photoluminescence characteristics observed in the BCP/PAA-Zn films excited with a wavelength of 250 nm indicated the successful loading of the BCP dye during the self-aggregation of the PAA-Zn film.

Advancing energy storage and supercapacitor applications through the development of Li+-doped MgTiO3 perovskite nano-ceramics.

Perovskite oxide materials, specifically MgTiO3 (MT) and Li-doped MgTiO3 (MTxLi), were synthesized via a sol-gel method and calcination at 800 °C. This study explores the impact of varying Li doping levels (x = 0, 0.01, 0.05, and 0.1) on the crystalline structure and properties of MgTiO3. X-ray diffraction analysis revealed a well-defined rhombohedral MgTiO3 phase. Optical diffuse reflectance measurements provided insights into energy gap values, refractive index, and dielectric constant. Li+ doping enhanced the electrical properties of MgTiO3, with a notable phase transition observed at 50 °C. The study investigated impedance and AC conductivity under varying temperature and frequency conditions (25-120 °C, 4 Hz to 8 MHz). Electrochemical analysis through cyclic voltammetry and electrochemical impedance spectroscopy confirmed highly electrocatalytic properties for MTxLi, particularly when modified onto screen-printed electrodes. This work not only advances the understanding of Li-doped MgTiO3 nanostructures but also highlights their significant potential for direct electrochemical applications, particularly in the realm of energy storage.

Optimizing magnetic, dielectric, and antimicrobial performance in chitosan-PEG-Fe2O3@NiO nanomagnetic composites.

There is a growing interest in eco-friendly and cost-effective organic-inorganic nanocomposites due to their alignment with the principles of "green" chemistry, as well as their biocompatibility and non-toxicity. This study focused on producing Chitosan-PEG-Fe2O3@NiO nanomagnetic composites to improve the stability, dielectric properties, and antimicrobial effectiveness of these nanocomposite materials. The process involved synthesizing Fe2O3@NiO via sol-gel and polymerizing chitosan-PEG. The nanocomposites were characterized by XRD, TEM, FTIR, optical, dielectric, and VSM. Incorporating Fe2O3@NiO significantly improved stability, and the interaction with Fe2O3 during the sol-gel process facilitated the formation of NiFe2O4 with an increase in the crystallinity within the chitosan-PEG matrix. The study examined optical and dielectric properties, highlighting that the 3 NiO-doped chitosan-PEG-Fe2O3 composites had high electrical conductivity (1.8 ∗ 10-3 S/cm) and a significant dielectric constant (106 at low frequencies). As the ratio of NiO NPs within the chitosan-PEG-Fe2O3 increases, the energy band gap of chitosan-PEG-Fe2O3 films decreases up to 3.7 eV. This decrease is owing to the quantum confinement effect. These composites also demonstrated improved antimicrobial activity against E. coli and S. aureus and higher activity in the presence of nanomagnetic particles. The minimum inhibitory concentrations of CS-PEG-Fe2O3/NiO NPs against (Bacillus cereus, M. luteus, S. aureus and (S. enterica, H. pylori, E. coli) were (22-35 mm) and (21-34 mm), respectively.

Humidity sensing using Zn(1.6 - x)Na0.4CuxTiO4 spinel nanostructures.

In this paper, we present a humidity sensing material based on nanostructured Zn(1.6 - x)Na0.4CuxTiO4 spinel to enhance optical and sensitivity performance. Nano-porous of Zn (1.6 - x) Na0.4CuxTiO4 spinel were synthesized using sol gel reactions and calcined at 700 °C. The nanostructures of Zn(1.6 - x)Na0.4CuxTiO4 spinel underwent thorough characterization through multiple techniques. X-ray diffractometry (XRD) coupled with Rietveld refinement using FullProf software, transmission electron microscopy (TEM), Raman Spectroscopy, and optical analysis were employed to assess various aspects of the nanostructures. These techniques were utilized to determine the phase composition, particle size distribution, chemical bonding, and the tunable band gap of the nanostructures. The X-ray diffraction (XRD) analysis of Zn(1.6 - x)Na0.4CuxTiO4 samples revealed well-defined and prominent peaks, indicating a highly crystalline cubic spinel structure. The lattice parameter was decreased from 8.4401 to 8.4212 Å with increasing Cu content from 0 to 1.2 mol%. UV-visible diffuse reflectance spectra were employed to investigate the optical characteristics of copper-doped Zn1.6Na0.4TiO4. The applicability of Cu@NaZT spinel nanostructures in humidity sensors was evaluated at ambient conditions. The fabricated sensor was investigated in a wide span of humidity (11-97%). The examined sensor demonstrates a low hysteresis, excellent repeatability, fast response and recovery. The response and recovery times were estimated to be 20 s and 6 s respectively. The highest sensitivity was achieved at 200 Hz. The proposed sensor can be coupled easily with electronic devices as the humidity-impedance relationship is linear.

Modifiable diarrhoea risk factors in Egyptian children aged <5 years.

By conducting a case-control study in two university hospitals, we explored the association between modifiable risk behaviours and diarrhoea. Children aged <5 years attending outpatient clinics for diarrhoea were matched by age and sex with controls. Data were collected on family demographics, socioeconomic indicators, and risk behaviour practices. Two rectal swabs and a stool specimen were collected from cases and controls. Samples were cultured for bacterial pathogens using standard techniques and tested by ELISA to detect rotavirus and Cryptosporidium spp. Four hundred cases and controls were enrolled between 2007 and 2009. The strongest independent risk factors for diarrhoea were: presence of another household member with diarrhoea [matched odds ratio (mOR) 4.9, 95% CI 2.8-8.4] in the week preceding the survey, introduction to a new kind of food (mOR 3, 95% CI 1.7-5.4), and the child being cared for outside home (mOR 2.6, 95% CI 1.3-5.2). While these risk factors are not identifiable, in some age groups more easily modifiable risk factors were identified including: having no soap for handwashing (mOR 6.3, 95% CI 1.2-33.9) for children aged 7-12 months, and pacifier use (mOR 1.9, 95% CI 1.0-3.5) in children aged 0-6 months. In total, the findings of this study suggest that community-based interventions to improve practices related to sanitation and hygiene, handwashing and food could be utilized to reduce the burden of diarrhoea in Egyptian children aged <5 years.

Synthesis and characterization of chitosan-corn starch-SiO2/silver eco-nanocomposites: Exploring optoelectronic and antibacterial potential.

This work discusses the physicochemical and antimicrobial characteristics of chitosan-corn starch eco-nanocomposites integrated with silica@Ag nano-spheres. These composites were synthesized through sol-gel polymerization and subsequently exposed to simulated body fluid (SBF). The incorporation of Ag into the eco-nanocomposites led to a decrease in diffuse reflectance across the entire wavelength range. The dielectric permittivity exhibited an increase up to 52.1 at a frequency of 100 kHz, while the ac conductivity reached a value of 5.2 ∗ 10-6 (S cm-1) at the same frequency for the sample with the highest Ag content. The study utilized XRD and FTIR techniques to examine the materials before and after in vitro testing and evaluated the antibacterial properties of the eco-nanocomposites against several pathogenic microorganisms, including Staphylococcus haemolyticus, Staphylococcus aureus, Klebsiella pneumoniae, and Escherichia coli, using the agar diffusion method. The eco-nanocomposites demonstrated bioactivity by forming a hydroxy appetite layer on their surfaces and were capable of releasing silver (Ag) at concentrations of 1.3, 1.9, and 2.5 mol%. This study suggests that chitosan-corn starch-SiO2-based doped with Ag eco-nanocomposite has the potential for various applications, including biomedical and environmental fields, where their antibacterial properties can be utilized to combat harmful microorganisms.

Construction and characterization of nano-oval BaTi0.7Fe0.3O3@NiFe2O4 nanocomposites as an effective platform for the determination of H2O2.

Talented di-phase ferrite/ferroelectric BaTi0.7Fe0.3O3@NiFe2O4 (BFT@NFO) in oval nano-morphology was chemically synthesized using controlled sol-gel processes and calcined at 600 °C. The effects of shielding using NiFe2O4 (NFO) nanoparticles on the microstructure, phase transition, thermal, and relative permittivity of BaTi0.7Fe0.3O3 (BTF) nano-perovskite were systematically explored. X-ray diffraction patterns and Full-Prof software exhibited the forming of the BaTi2Fe4O11 hexagonal phase. TEM and SEM images demonstrated that the coating of BaTi0.7Fe0.3O3 has been successfully controlled with exquisite nano-oval NiFe2O4 shapes. The NFO shielding can significantly promote the thermal stability and the relative permittivity of BFT@NFO pero-magnetic nanocomposites and lowers the Curie temperature. Thermogravimetric and optical analysis were used to test the thermal stability and estimate the effective optical parameters. Magnetic studies showed a decrease in saturation magnetization of NiFe2O4 NPs compared to their bulk system, which is attributed to surface spin disorder. Herein, characterization and the sensitive electrochemical sensor were constructed for the evaluation of peroxide oxidation detection using the chemically adjusted nano-ovals barium titanate-iron@nickel ferrite nanocomposites. Finally, The BFT@NFO exhibited excellent electrochemical properties which can be ascribed to this compound possessing two electrochemical active components and/or the nano-ovals structure of the particles which can further improve the electrochemistry through the possible oxidation states and the synergistic effect. The result advocates that when the BTF is shielded with NFO nanoparticles the thermal, dielectric, and electrochemical properties of nano-oval BaTi0.7Fe0.3O3@NiFe2O4 nanocomposites can be synchronously developed. Thus, the production of ultrasensitive electrochemical nano-systems for the determination of hydrogen peroxide is of extensive significance.

Knowledge, attitudes and practices towards family planning among women in the rural southern region of Jordan.

Data about family planning among women in rural and remote areas of Jordan are lacking. This study explored the prevalence of use and knowledge and attitudes towards family planning among rural Jordanian women. A descriptive study was conducted with 807 ever-married women aged 15-49 years in a household survey of 29 villages in the southern region of Jordan. The most common contraceptive methods ever used were oral contraceptive pills (31.1%); intrauterine device (24.8%) and withdrawal (19.5%). Of the women interviewed, 37% were currently using contraception. Being pregnant (11%) and breastfeeding (10%) were the most reported reasons for not using contraceptives. None of the women reported obtaining supplies or the cost of them as barriers, while opposition from husband or family members or religious reasons were reported by less than 1% of the women. About 95% of the women agreed that using family planning had positive advantages for health. The results highlight some educational needs among these women.

Evaluating the psychosocial and mental health consequences of abuse among Jordanian women.

This cross-sectional, descriptive, correlational study evaluated the mental health consequences of abuse among Jordanian women. Standard tools were used to collect data from 93 abused women seeking help at a welfare centre in relation to forms of abuse, depression, coping, suicidal ideation, substance use, social support and self-efficacy. The most commonly reported form of abuse was psychological abuse. Applying the Beck Depression Inventory showed that 38.7% of the abused women had moderate to severe levels of depression. Although half the women had a low level of perceived social support, abused Jordanian women reported moderate to very high levels of self-efficacy and used approach coping more frequently than avoidance coping strategies. Using the Modified Scale for Suicide Ideation, 15.7% of the women reported that the desire for death was stronger than the desire for life. Abused women in Jordan face mental health and psychosocial risks that could compromise their quality of life.

Ecofriendly synthesis and characterization of Ni2+ codoped silica magnesium zirconium copper nanoceramics for wastewater treatment applications.

This article investigates the effect of Ni2+ content on structural (XRD, XPS), morphological (TEM), and magnetic behaviors of silica magnesium zirconium copper nanoceramics calcined at 800 °C. The sol-gel route is followed for the silica magnesium zirconium copper/(0.0-0.7) Ni2+ samples preparation. X-ray photoelectron spectroscopy is employed to analyze the chemical states of elements for the samples. The three representative binding energy magnitudes for O, Ni, and Cu reside at 534, 857, and 979 eV, consecutively. The saturation magnetization constricts with the elevation of Ni2+ content, while the magnetic hysteresis loop resembles the superparamagnetic attitude. The optical spectra present the possibility of direct and indirect transitions in the prepared nanoceramics. Energy gap (value and type), refractive index, and real and imaginary dielectric constant were extracted. The energy gap approaches 3.75 eV and 3.71 eV for direct and indirect transitions correspondingly with (0.7) Ni2+. The antimicrobial and the toxicity performance of all inspected nanocomposites were conducted against pathogenic microbes. The attained results evidenced that SMZC-0.7Ni possesses energetic antimicrobial potential against all targeted microbes. The investigated SMZC-0.7Ni nanocomposite functioned to eradicate frequent waterborne pathogens in wastewater at an appropriate dose (100 mg/L), demonstrating that SMZC can be utilized as a competent disinfectant in the municipal wastewater decontamination process. Inherently, SMZC-0.7Ni can be employed as an excellent nano-weapon against multiple dangerous microorganisms.

Talented Bi0.5Na0.25K0.25TiO3/oxidized cellulose films for optoelectronic and bioburden of pathogenic microbes.

We study the microstructure, optical, thermal, dielectric, and mechanical properties of flexible oxidized cellulose (OC) films loaded with different mass fractions of cubic structure Bi0.5Na0.25K0.25TiO3 by blending solution technique and casting method. The films were characterized using infrared, X-ray diffraction, scanning electron microscopy, and UV-visible spectroscopy. The optical results confirmed the formation of crystalline bismuth sodium titanate/OC semiconductor films with a direct energy bandgap (3.002-3.276 eV) and have the ability for optoelectronic applications. The dielectric constant and dielectric loss of OC /BNKT film decreased obviously with increasing frequency. However, the ferroelectric state of the BNKT and its correlation with structure verified the existence of a relaxer behavior to this ratio. OC film with 20% dopped BNKT displayed energetic bactericidal activity against Gram-positive and Gram-negative bacteria. The presented study suggested that this film can be used as an antibacterial packaging material to diminish packaging's adverse environmental impacts with non-cytotoxicity.

Children's knowledge of cancer diagnosis and treatment: Jordanian mothers' perceptions and satisfaction with the process.

BACKGROUND: The amount of information shared with children regarding their illness, as well as what knowledge children are entitled to know, varies widely among cultures. AIMS: This study aims to examine mothers' accounts of communication about cancer diagnosis to their children, how much children knew about their illnesses and how satisfied the mothers were with the method they used in communicating the diagnosis. METHODS: Using semi-structured interviews and open-ended questions, 51 mothers attending paediatric oncology clinics in Jordan were interviewed. Content analysis was used to analyse the data. FINDINGS: Mothers expressed a range of views about the forms of disclosure, including being clear about the diagnosis and its treatment and being secretive yet misconceptualizing the accounts of the illness. The median age for the children diagnosed with cancer was 11 years (interquartile range 7-16 years). Most of the mothers were offered no help with talking to their children about cancer diagnosis. Mothers who found it difficult to tell the news of the diagnosis to their children finally withheld the diagnoses from them. Those same mothers were unhappy and uncomfortable with the communication method they had used with children. CONCLUSION: This study emphasized the role of nurses' interaction with their child patients diagnosed with cancer. Nurses should not have an opinion about how and what children need to know about their illness, and preferably should take an active role in the process of communication between mothers and their children. Further work and research are needed in this field.

Structural, Magnetic, and Dielectric properties of Sr4Fe6O13 ferrite prepared of small crystallites.

A stable Sr4Fe6O13 was prepared as small crystallites by auto-combustion of a sol-gel in air followed by annealing the later at pertinent temperatures. A green sample, as annealed at elevated temperatures, yields a single Sr4Fe6O13 phase of tailored magnetic properties. The structural, morphological, magnetic and electrical properties were investigated by X-ray diffraction, transmission electron microscopy, vibrating sample magnetometer, and broadband dielectric spectrometer. Hard magnetic Sr4Fe6O13 properties arise with saturation magnetization Ms = 12.4 emu/g, coercivity Hc = 3956.7 Oe and squareness 0.512. Studies made at low temperatures reveals Ms decreasing on increasing temperature from 17.5 emu/g at 85 K down to 12.4 emu/g at 305 K, while Hc rises from 1483 Oe at 85 K to 1944 Oe at 305 K. The ac-conductivity follows the Jonscher relation. The dc-conductivity at high temperatures/low frequencies exhibits a plateau and it depends linearly on a characteristic frequency according to the Barton-Nakajima-Namikawa) relation.

Computational flow cytometry of planktonic populations for the evaluation of microbiological-control programs in district cooling plants.

Biofouling poses a serious concern for the district cooling (DC) industry. Current industry practises for monitoring biofouling continue to rely on culture-based methods for microbial enumeration, which are ultimately flawed. Computational flow cytometric (cFCM) analyses, which offer enhanced reproducibility and streamlined analytics versus conventional flow cytometry were applied to samples taken from 3 sites in each of 3 plants over a 5-week sampling program. We asked whether the application of cFCM to monitoring planktonic community dynamics in DC plants could be able to provide sufficient information to enhance microbiological-control strategies at site and inform about plant performance impacts. The use of cFCM enabled the evaluation of biocide dosing, deep cleaning treatment efficiencies and routes of microbial ingress into the studied systems. Additionally, inherent risks arising from the reintroduction of microbiological communities into recently cleaned WCT basins from contaminated cooling waters were identified. However, short-term dynamics did not relate with plant performance metrics. In summary, the insights offered by this approach can inform on plant status, enable evaluations of microbial loads during biofouling mitigation programs and, ultimately, enhance industry management of the biofouling process.

Silencing of tissue factor by antisense deoxyoligonucleotide mitigates thioacetamide-induced liver injury.

BACKGROUND: Retinoid receptors (RRs), RAR-α and RXR-α, work as transcription factors that regulate cell growth, differentiation, survival, and death. Hepatic stellate cells (HSCs) store retinoid and release its RRs as lipid droplets upon their activation. PURPOSE: We test the hypothesis that loss of retinoid receptors RAR-α and RXR-α from HSCs is dependent on tissue factor (TF) during thioacetamide (TAA)-induced liver injury. METHODS: Liver toxicity markers, TF, fibrin, cleaved caspase-3, and cyclin D1 as well as histopathology were investigated. RESULTS: Increased TF, fibrin, cleaved caspase-3, and cyclin D1 protein expression is seen in zone of central vein after TAA injection compared with vehicle-treated mice. A strong downregulation of RAR-α and RXR-α is seen in TAA-induced liver injury. In addition, histopathological obliteration and pericentral expression of cleaved caspase 3 and cyclin D1 are observed after TAA injection compared with the normal vehicle-treated mice. No changes have been seen in TAA/TF-sense (SC) in whole parameters compared with TAA-treated animals. TAA/TF-antisense (AS)-treated mice show normal expression of all parameters and normal histopathological features when compared with the control mice. In conclusion, this study declares that the strong downregulation of RAR-α and RXR-α may cause liver injury and particularly activation of HSCs in TAA-induced toxicity. TF-AS treatment not only downregulates TF protein expression but also alleviates loss of liver RAR-α and RXR-α and suppresses the activated apoptosis signals in TAA-induced liver toxicity. Finally, TF and RAR-α/RXR-α are important regulatory molecules in TAA induced acute liver injury.

Heartworm and Wolbachia: therapeutic implications.

A safer, more effective adulticidal treatment and a safe method for reducing microfilaremia and breaking transmission of heartworm disease early in the treatment are needed. The present study evaluated efficacy of ivermectin (IVM) and doxycycline (DOXY) alone or together (with or without melarsomine [MEL]) in dogs with induced adult heartworm infection and assessed the ability of microfilariae from DOXY-treated dogs to develop to L3 in Aedes aegypti mosquitoes and subsequently to become reproductive adults in dogs. Thirty beagles were each infected with 16 adult heartworms by intravenous transplantation. Six weeks later, dogs were ranked by microfilarial count and randomly allocated to 6 groups of 5 dogs each. Beginning on Day 0, Group 1 received IVM (6 mcg/kg) weekly for 36 weeks. Group 2 received DOXY (10 mcg/(kgday)) orally Weeks 1-6, 10-11, 16-17, 22-25, and 28-33. Groups 3 and 5 received IVM and DOXY according to doses and schedules used for Groups 1 and 2. At Week 24, Groups 3 and 4 received an intramuscular injection of MEL (2.5 mg/kg), followed 1 month later by two injections 24h apart. Group 6 was not treated. Blood samples were collected for periodic microfilaria counts and antigen (Ag) testing (and later immunologic evaluation and molecular biology procedures). Radiographic and physical examinations, hematology/clinical chemistry testing, and urinalysis were done before infection, before Day 0, and periodically during the treatment period. At 36 weeks, the dogs were euthanized and necropsied for worm recovery, collection of lung, liver, kidney, and spleen samples for examination by immunohistochemistry and conventional histological methods. All dogs treated with IVM + DOXY (with or without MEL) were amicrofilaremic after Week 9. Microfilarial counts gradually decreased in dogs treated with IVM or DOXY, but most had a few microfilariae at necropsy. Microfilarial counts for dogs treated only with MEL were similar to those for controls. Antigen test scores gradually decreased with IVM + DOXY (with or without MEL) and after MEL. Antigen scores for IVM or DOXY alone were similar to controls throughout the study. Reduction of adult worms was 20.3% for IVM, 8.7% for DOXY, 92.8% for IVM + DOXY + MEL, 100% for MEL, and 78.3% for IVM + DOXY. Mosquitoes that fed on blood from DOXY-treated dogs had L3 normal in appearance but were not infective for dogs. Preliminary observations suggest that administration of DOXY+IVM for several months prior to (or without) MEL will eliminate adult HW with less potential for severe thromboembolism than MEL alone.