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high-yield c11-oxidation of hydrocortisone by establishment of an efficient whole-cell system in bacillus megaterium.steroidal compounds are one of the most widely marketed pharmaceutical products. chemical synthesis of steroidal compounds faces many challenges, including the requirement for multiple chemical steps, low yield and selectivity in several synthesis steps, low profitability and the production of environmental pollutants. consequently, in recent decades there has been growing interest in the use of microbial systems to produce pharmaceutical compounds. several microbial systems have recently been d ...201931212031
dexamethasone-loaded injectable silk-polyethylene glycol hydrogel alleviates cisplatin-induced ototoxicity.background: cisplatin is an extensively used anti-neoplastic agent for the treatment of various solid tumors. however, a high incidence of severe ototoxicity is accompanied by its use in the clinic. currently, no drugs or therapeutic strategies have been approved for the treatment of cisplatin-induced ototoxicity by the fda. purpose: the purpose of this study was to investigate the otoprotective effects of dexamethasone (dex)-loaded silk-polyethylene hydrogel (dex-silk) following round window me ...201931239676
ocular anti-inflammatory activity of prednisolone acetate loaded chitosan-deoxycholate self-assembled nanoparticles.background and purpose: conventional topical ophthalmic aqueous solutions and suspensions are often associated with low bioavailability and high administration frequency, pulsatile dose and poor exposure to certain ocular parts. the aim of this study was to develop an ophthalmic nanoparticles loaded gel, for delivering prednisolone acetate (pa), to increase dosing accuracy, bioavailability, and accordingly, efficiency of pa in treating inflammatory ocular diseases. methods: a novel formulation o ...201931239660
effects of the long wavelength-filtered continuous spectrum on natural refractive development in juvenile guinea pigs.to investigate the effects of spectral composition and light intensity on natural refractive development in guinea pigs.201931236341
effect of gamma irradiation on microbial decontamination, crude nutrient content, and mineral nutrient composition of laboratory animal diets.laboratory animal models are an important part of test design. certain conditions such as microbial contamination in diets of these models could affect the results of experiments. one of the most important routes that predispose to contamination is generated through feeding of laboratory animals. this study aimed to show the effect of gamma irradiation in reducing bacteria concentrations, crude nutrient content, and concentrations of some minerals and trace elements in laboratory animal diets. l ...201931232567
prokaryotic sphinx replication sequences are conserved in mammalian brain and participate in neurodegeneration.a new class of viral mammalian slow progressive hidden infections of variable (x) latency ("sphinx") dnas, represented by the 1.8 and 2.4 kb nuclease-protected circular elements, were discovered in highly infectious cytoplasmic particles isolated from creutzfeldt-jakob disease (cjd) and scrapie samples. these dnas contained replication initiation sequences (reps) with approximately 70% homology to those of environmental acinetobacter phage. antibodies against rep peptides from the 1.8 kb dna hig ...201931231867
entering the spotlight: chitosan oligosaccharides as novel activators of caccs/tmem16a.calcium-activated chloride channels (caccs)/tmem16a control diverse fundamental physiological functions, and abnormal function of tmem16a will lead to various diseases including asthma, hypertension, gastrointestinal hypomotility and cancers. therefore, tmem16a as drug targets for related diseases has been increasingly concerned by researchers. in this work, cos were reported as novel natural activators of tmem16a. it was demonstrated that cos can activate tmem16a in a concentration dependent ma ...201931229561
mast cell degranulation and fibroblast activation in the morphine-induced spinal mass: role of mas-related g protein-coupled receptor signaling.as the meningeally derived, fibroblast-rich, mass-produced by intrathecal morphine infusion is not produced by all opiates, but reduced by mast cell stabilizers, the authors hypothesized a role for meningeal mast cell/fibroblast activation. using the guinea pig, the authors asked: (1) are intrathecal morphine masses blocked by opiate antagonism?; (2) do opioid agonists not producing mast cell degranulation or fibroblast activation produce masses?; and (3) do masses covary with mas-related g prot ...201931225809
proposal of ghs sub-categorization criteria for llna: brdu-elisa (oecd tg442b).the globally harmonized system of classification and labelling of chemicals (ghs) is a hazard classification and communication system for providing information on the safe handling of chemicals worldwide. while the ghs provides sub-categorization criteria for sensitizers when using the guinea pig maximization test/buehler test (oecd tg406) and the standard radioisotopic llna (oecd tg429), the sub-categorization criteria for llna: brdu-elisa (oecd tg442b) are not currently provided. in this study ...201931220472
ag85b/esat6-cfp10 adjuvanted with aluminum/poly-ic effectively protects guinea pigs from latent mycobacterium tuberculosis infection.the high global burden of tuberculosis (tb) underscores the urgent need for an effective tb vaccine since the only licensed bacillus calmette-guérin (bcg) vaccine is ineffective in preventing adult pulmonary tb and affords no protection against latent tb infection (ltbi). herein we investigated the potential of mycobacterium tuberculosis (mtb) antigen proteins aec comprised of ag85b and esat6-cfp10 proteins in conjunction with aluminum (al) and polyriboinosinic-polyribocytidylic acid (poly-ic) a ...201931266673
[effect of lipid-lowering activity of the natural original enzyme preparation in the experiment].the experimental study in vivo was aimed at evaluation of hypolipidemic action of the original natural microbial enzyme preparation of cholesterol oxidase (cho). in preliminary chronic experiments in rats, rabbits, dogs, low toxicity, good tolerability, and anti-atherosclerotic activity of the cho preparation were established. to assess the effect of cho under conditions of moderate, nutritional, atherogenic dyslipoproteinemia, experiments were carried out in rats, guinea pigs, and rabbits. it w ...201931258146
an advanced in silico modelling of the interaction between fscpx, an irreversible a1 adenosine receptor antagonist, and nbti, a nucleoside transport inhibitor, in the guinea pig atrium.in earlier studies, we generated concentration-response (e/c) curves with cpa (n6-cyclopentyladenosine; a selective a1 adenosine receptor agonist) or adenosine, in the presence or absence of s-(2-hydroxy-5-nitrobenzyl)-6-thioinosine (nbti, a selective nucleoside transport inhibitor), and with or without a pretreatment with 8-cyclopentyl-n3-[3-(4-(fluorosulfonyl)-benzoyloxy)propyl]-n1-propylxanthine (fscpx, a chemical known as a selective, irreversible a1 adenosine receptor antagonist), in isolat ...201931212849
insights figure for "differential cell proliferation and cell death during the urethral groove formation in guinea pig model". 201931212305
age‑associated variation in the expression and function of tmem16a calcium‑activated chloride channels in the cochlear stria vascularis of guinea pigs.the present study was designed to investigate the expression and function of transmembrane protein 16 (tmem16a), a calcium‑activated chloride channel (cacc), in the stria vascularis (sv) of the cochlea of guinea pigs at different ages, and to understand the role of caccs in the pathogenesis of presbycusis (age‑related hearing loss), the most common type of sensorineural hearing loss that occurs with natural aging. guinea pigs were divided into the following groups: 2 weeks (young group), 3 month ...201931257512
bacterial extracellular electron transfer occurs in mammalian gut.as a well-studied biochemical reduction process in environmental microbiology, extracellular electron transfer (eet) was recently discovered in bacteria closely related to human health, and orthologues of a flavin-based eet gene were found in the genomes of many species across firmicutes, a major phylum in mammalian gut microbiota. however, eet has not yet been confirmed to occur in mammalian gut, the presence of which may have broad physiological influences. toward this end, here we first confi ...201931512863
early alterations of endothelial nitric oxide synthase expression patterns in the guinea pig cochlea after noise exposure.constitutively expressed endothelial nitric oxide synthase (enos) is supposed to play a role in noise-induced nitric oxide (no)-production. it is commonly known that intense noise exposure results in inducible nos (inos) expression and increased no-production, but knowledge about a contribution of the enos isoform is still lacking. effects of noise exposure on enos immunolabeling were determined in male guinea pigs (n=24). for light microscopic analysis, 11 animals were exposed to 90 db for 1 hr ...201931510846
the rho-independent transcription terminator for the pora gene enhances expression of the major outer membrane protein and campylobacter jejuni virulence in abortion induction.campylobacter jejuni is a leading cause of foodborne illnesses worldwide. its pora gene encodes the major outer membrane protein (momp) that is abundantly expressed and has important physiological functions, including a key role in systemic infection and abortion induction in pregnant animals. despite the importance of pora in c. jejuni pathogenesis, mechanisms modulating its expression levels remain elusive. at the 3' end of the pora transcript, there is a rho-independent transcription terminat ...201931570559
characterization of changes in the configuration of action potentials in the mouse, guinea pig, and pig sinoauricular node after application of channel blockers of the rapid and slow delayed rectifier potassium currents.we hypothesized that the repolarization phase of action potentials (aps) in mammals with large body mass and high cardiac output could not be reliably controlled by only one of the delayed rectifier potassium ik current components. to test this hypothesis experimentally, we performed a comparative study of the response of ap phases to the rapid ikr channels blocker e-4031 and slow iks blocker chromanol 293b in aps spontaneously generated in strips of sinoauricular (sa) tissue from mouse, guinea ...201931566191
dynamic changes of activator protein 1 and collagen i expression in the sclera of myopia guinea pigs.to investigate the dynamic changes of activator protein 1 (ap1) and collagen i expression in the sclera of form-deprivation myopic model in guinea pigs.201931456916
effect of luteolin on apoptosis, mapk and jnk signaling pathways in guinea pig chondrocyte with osteoarthritis.osteoarthritis (oa) is a degenerative joint disease usually seen in the elderly, which incidence increases with age. its pathogenesis and underlying mechanism are still unclear. the disease severely affects the physical health and life quality of patients, thereby constituting a huge economic burden to family and society. luteolin (lut) is a natural flavonoid with multiple pharmacological properties. many plants containing lut have been applied in the treatment of several inflammation-related di ...201931472053
effects of commercially available whitening creams on the epidermal thickness of guinea pig skin.to determine the effects of commonly used commercial skin lightening creams on the thickness of epidermis of guinea pig skin.201931455470
a single immunogenicity assay for testing potency of combination dtap vaccines: simultaneous quantitation of anti-dt, anti-tt, anti-ptxd and anti-fha antibodies in guinea-pig serum with a luminex®-xmap® bead-based serological assay.the diphtheria toxoid (dt), tetanus toxoid (tt), and acellular pertussis (ap) single immunogenicity assay (dtap sia) is a luminex®-xmap®-bead-based multiplex immunoassay for estimating the potency of dtap pediatric combination vaccines in guinea pigs. this manuscript describes the validation of this assay for the simultaneous quantitation of anti-diphtheria toxoid (anti-dt), anti-tetanus toxoid (anti-tt), anti-pertussis toxoid (anti-ptxd), and anti-filamentous hemagglutinin (anti-fha) antibodies ...201931451353
successful application of prime and pull strategy for a therapeutic hsv vaccine.one promising approach for a herpes simplex virus vaccine uses a vaccine to prime and a chemoattractant to pull immune cells into the genital tract. we evaluated subunit vaccines (prime) and imiquimod (pull) in the guinea pig (gp) model of recurrent herpes simplex virus type-2 (hsv-2). following vaginal hsv-2 infection, gps were vaccinated with various combination of glycoproteins and adjuvant with or without subcutaneous or local applications of imiquimod after infection. animals were examined ...201931396405
the effect of helicobacter pylori infection and different h. pylori components on the proliferation and apoptosis of gastric epithelial cells and fibroblasts.helicobacter pylori colonizes the human gastric mucosa, causing chronic inflammation, peptic ulcers and gastric cancer. a cascade of harmful processes results from the interaction of these bacteria with the gastric epithelium.201931390383
incomplete influenza a virus genomes occur frequently but are readily complemented during localized viral spread.segmentation of viral genomes into multiple rnas creates the potential for replication of incomplete viral genomes (ivgs). here we use a single-cell approach to quantify influenza a virus ivgs and examine their fitness implications. we find that each segment of influenza a/panama/2007/99 (h3n2) virus has a 58% probability of being replicated in a cell infected with a single virion. theoretical methods predict that ivgs carry high costs in a well-mixed system, as 3.6 virions are required for repl ...201931387995
analysis of nickel distribution by synchrotron radiation x-ray fluorescence in nickel-induced early- and late-phase allergic contact dermatitis in hartley guinea pigs.nickel-induced allergic contact dermatitis (ni-acd) is a global health problem. more detailed knowledge on the skin uptake of haptens is required. this study aimed to investigate the penetration process and distribution of nickel in skin tissues with late phase and early phase of ni-acd to understand the mechanisms of metal allergy.201931373908
maastricht antiarrhythmic drug evaluator (manta): a computational tool for better understanding of antiarrhythmic drugs.cardiac arrhythmias are a global health burden, contributing significantly to morbidity and mortality worldwide. despite technological advances in catheter ablation therapy, antiarrhythmic drugs (aads) remain a cornerstone for the management of cardiac arrhythmias. experimental and translational studies have shown that commonly used aads exert multiple effects in the heart, the manifestation of which strongly depends on the exact experimental or clinical conditions. this diversity makes the opti ...201931493513
frequency of owner-reported bacterial infections in pet guinea pigs.domestic guinea pigs suffer morbidity and mortality due to a range of bacterial infections amongst other causes. microorganisms such as bordetella bronchiseptica and streptococcus pneumoniae are commonly implicated in respiratory disease; however, there is a lack of research surrounding the prevalence of these bacterial infections. the aim of this study was to investigate the frequency with which owners reported bacterial infections in pet guinea pigs and to assess owner knowledge of correct hus ...201931487781
the effects of transplanted mesenchymal stem cells treated with 17-b estradiol on experimental autoimmune encephalomyelitis.the present study was conducted aimed at exploring the modulatory effects of 17-b estradiol (17-bed) on mesenchymal stem cells (mscs) in the eae (experimental autoimmune encephalomyelitis) animal model of multiple sclerosis (ms). following the isolation of bone marrow-derived mscs from the bilateral femurs and tibias of the male wistar rats, the cells were harvested and cultured in the presence of 100 nm 17-bed for 24 h. eae was induced in male wistar rats (8-12 weeks old) using guinea pig spina ...201931555971
electrophysiological characterization of a small molecule activator on human ether-a-go-go-related gene (herg) potassium channel.the human ether-a-go-go-related gene (herg) encodes the k+ channel that carries the rapid component of the delayed rectifier current in the human heart. reduction of herg activity induced by gene mutations or pharmacological inhibition is responsible for the type 2 form of long qt syndrome in patients which can develop into ventricular arrhythmia and sudden cardiac death. therefore, pharmacological activation of herg may lead to therapeutic potential for cardiac arrhythmias. in this study we cha ...201931481348
therapeutic efficacy of equine botulism heptavalent antitoxin against all seven botulinum neurotoxins in symptomatic guinea pigs.botulism neurotoxins are highly toxic and are potential agents for bioterrorism. the development of effective therapy is essential to counter the possible use of these toxins in military and bioterrorism scenarios, and to provide treatment in cases of natural intoxication. guinea pigs were intoxicated with a lethal dose of botulinum neurotoxin serotypes a, b, c, d, e, f or g, and at onset of the clinical disease intoxicated animals were treated with either bat® [botulism antitoxin heptavalent (a ...201931527885
rat model of ménière's attack: intratympanic injection of potassium chloride produces direction-changing spontaneous nystagmus and hearing fluctuations.the major symptoms of ménière's disease are episodic vertigo, fluctuating hearing loss, and tinnitus. direction-changing spontaneous nystagmus is a characteristic vestibular finding in ménière's disease. in the acute stage, spontaneous nystagmus beating to the affected side (irritative nystagmus) is often observed, while paralytic nystagmus beating to the healthy side is found in the chronic stage. this direction-changing nystagmus can be reproduced in guinea pigs by increasing the potassium ion ...201931522181
involvement of the persistent na+ current in the diastolic depolarization and automaticity of the guinea pig pulmonary vein myocardium.the role of the na+ current in the automaticity of the pulmonary vein myocardium was examined in isolated guinea pig pulmonary vein cardiomyocytes and tissue preparations. tetrodotoxin inhibited the automaticity of pulmonary vein tissue preparations by suppressing the diastolic depolarization of the action potential. atx-ii, which increased the density of persistent component of the na+ current (late ina), induced a depolarization of the resting membrane potential followed by spontaneous firing ...201931521490
intracochlear plga based implants for dexamethasone release: challenges and solutions.the effective treatment of diseases of the inner ear is currently an unmet medical need. local controlled drug delivery to the cochlea is challenging due to the hidden location, small volume and high sensitivity of this organ. a local intracochlear delivery of drugs would avoid the problems of intratympanic (extracochlear) drug application, but is more invasive. the requirements for such a delivery system include a small size and appropriate flexibility. the delivery device must be rigid enough ...201931517280
inclusion of the viral pentamer complex in a vaccine design greatly improves protection against congenital cytomegalovirus in the guinea pig model.a vaccine against congenital cytomegalovirus (ccmv) is a high priority. the guinea pig is a small-animal model for ccmv. a disabled infectious single-cycle (disc) viral vaccine strain based on a guinea pig cytomegalovirus (gpcmv) capsid mutant was evaluated. a previous version of this vaccine did not express the gh/gl-based pentamer complex (pc) and failed to fully protect against ccmv. the pc is necessary for gpcmv epithelial cell/trophoblast tropism and congenital infection and is a potentiall ...201931484753
glutathione supplementation of parenteral nutrition prevents oxidative stress and sustains protein synthesis in guinea pig model.peroxides contaminating parenteral nutrition (pn) limit the use of methionine as a precursor of cysteine. thus, pn causes a cysteine deficiency, characterized by low levels of glutathione, the main molecule used in peroxide detoxification, and limited growth in individuals receiving long-term pn compared to the average population. we hypothesize that glutathione supplementation in pn can be used as a pro-cysteine that improves glutathione levels and protein synthesis and reduces oxidative stress ...201931484318
sustained-release triamcinolone acetonide hydrogels reduce hearing threshold shifts in a model for cochlear implantation with hearing preservation.in recent years, the preservation of residual hearing has become a major factor in patients undergoing cochlear implantation (ci). in studies attempting to pharmaceutically improve hearing preservation rates, glucocorticoids (gcs) applied perioperatively in many institutions have emerged as a promising treatment regimen. although dexamethasone is most commonly used and has been applied successfully by various research groups, recently pharmacological properties have been reported to be relativel ...201931574511
fsh1 regulates the phenotype and pathogenicity of the pathogenic dermatophyte microsporum canis.microsporum canis (m. canis) is a common pathogen that causes tinea capitis and is present worldwide. the incidence of m. canis infection, particularly tinea capitis, has been increasing in china. in our previous studies, family of serine hydrolases 1 (fsh1) was identified as a potential virulence factor in tinea capitis infection caused by m. canis. to determine the function of this gene in m. canis, fsh1 was knocked down using double‑stranded rna interference mediated by agrobacterium tumefaci ...201931573050
lipoarabinomannan in active and passive protection against tuberculosis.glycolipids of the cell wall of mycobacterium tuberculosis (mtb) are important immunomodulators in tuberculosis. in particular, lipoarabinomannan (lam) has a profound effect on the innate immune response. lam and its structural variants can be recognized by and activate human cd1b-restricted t cells, and emerging evidence indicates that b cells and antibodies against lam can modulate the immune response to mtb. anti-lam antibodies are induced during mtb infection and after bacille calmette-gueri ...201931572351
prevailing effects of ibutilide on fast delayed rectifier k+ channel.effects of ibutilide, a class iii antiarrhythmic drug, on delayed rectifier potassium currents (ik) in freshly isolated guinea pig ventricular myocytes were studied. experiments were performed using the whole-cell configuration of patch-clamp technique under blockade of l-type calcium currents (cav1). ibutilide at concentrations ranging between 10 nm and 100 µm inhibited ikr in dose-dependent manner with a half maximal effective concentration of 2.03 ± 0.74 µm (n = 5-10). the amplitude of tail c ...201931584122
ultrastructural and chemical composition of dentin and enamel in lab animals.human tooth is clinically the most appropriate material that can be used for in-vitro dental research. however, there are limitations and drawbacks for using human teeth. therefore, alternatives to samples of human teeth for dental studies are necessary.201931579692
lethal infection of lassa virus isolated from a human clinical sample in outbred guinea pigs without adaptation.lassa virus (lasv), a member of the family arenaviridae, is the causative agent of lassa fever. lassa virus is endemic in west african countries, such as nigeria, guinea, liberia, and sierra leone, and causes outbreaks annually. lassa fever onset begins with "flu-like" symptoms and may develop into lethal hemorrhagic disease in severe cases. although lassa virus is one of the most alarming pathogens from a public health perspective, there are few licensed vaccines or therapeutics against lassa f ...201931554720
kenneth mellanby commander of the order of the british empire (cbe) (1908-1993). the facts about scabies.kenneth mellanby was a distinguished biologist specialising in entomology. he helped to establish the first university in nigeria and undertook pioneering work on the use of insecticides in agriculture. however, he will best be remembered for a series of experiments which he undertook on human volunteers during the second world war. these experiments established the mechanism of transmission of scabies and allowed its effective control at a time when the condition had reached epidemic proportion ...201931554454
ipad-loaded n-trimethyl chitosan nanoparticles can efficiently protect guinea pigs against shigella flexneri.shigella flexneri is a pathogen responsible for shigellosis around the world, especially in developing countries. many immunogenic antigens have been introduced as candidate vaccines against shigella, including n-terminal region of ipad antigen (nipad).201931552830
the exploitation of professional "guinea pigs" in the gig economy: the difficult road from consent to justice. 201931543031
mapping of shigella flexneri's tissue distribution and type iii secretion apparatus activity during infection of the large intestine of guinea pigs.shigella spp. are bacterial pathogens that invade the human colonic mucosa using a type iii secretion apparatus (t3sa), a proteinaceous device activated upon contact with host cells. active t3sas translocate proteins that carve the intracellular niche of shigella spp. nevertheless, the activation state of the t3sa has not been addressed in vivo. here, we used a green fluorescent protein transcription-based secretion activity reporter (tsar) to provide a spatio-temporal description of s. flexneri ...201931578543
extracellular ph and intracellular phosphatidylinositol 4,5-bisphosphate control cl- currents in guinea pig detrusor smooth muscle cells.cl- channels serve as key regulators of excitability and contractility in vascular, intestinal, and airway smooth muscle cells. we recently reported a cl- conductance in detrusor smooth muscle (dsm) cells. here, we used the whole cell patch-clamp technique to further characterize biophysical properties and physiological regulators of the cl- current in freshly isolated guinea pig dsm cells. the cl- current demonstrated outward rectification arising from voltage-dependent gating of cl- channels r ...201931577513
comparative immunogenicity and efficacy of thermostable (lyophilized) and liquid formulation of anthrax vaccine candidate av7909.the anthrax vaccine candidate av7909 is being developed as a next-generation vaccine for a post-exposure prophylaxis (pep) indication against anthrax. av7909 consists of the anthrax vaccine adsorbed (ava) (emergent biosolutions inc., lansing, mi) bulk drug substance adjuvanted with the immunostimulatory oligodeoxynucleotide (odn) compound, cpg 7909. the addition of cpg 7909 to ava enhances both the magnitude and the kinetics of antibody responses in animals and human subjects, making av7909 a su ...201931530467
surface plasmon resonance immunosensor for label-free detection of birc5 biomarker in spontaneously occurring canine mammary tumours.we report detection of baculoviral inhibitor of apoptosis repeat containing-5 (birc5) protein biomarker in dog serum by label-free surface plasmon resonance (spr) immunosensor. initially, overexpression of birc5 in canine mammary tumour (cmt) tissues was confirmed by real-time pcr. recombinant birc5 was produced and protein specific antibodies developed in guinea pig specifically reacted with native protein in immunohistochemistry and immunocytochemistry. spr immunosensor was developed by fabric ...201931530877
susceptibility of rickettsia rickettsii to tigecycline in a cell culture assay and animal model for rocky mountain spotted fever.rocky mountain spotted fever (rmsf), caused by rickettsia rickettsii, is a severe tick-borne infection endemic to the americas. oral doxycycline is effective, but during severe life-threatening disease, intravenous therapy is recommended. unfortunately, intravenous formulations of doxycycline are not always available. therefore, we aimed to determine the susceptibility of r. rickettsii to an alternative parenteral agent, tigecycline, in vitro and in vivo. to determine the minimum inhibitory conc ...201931516114
intranasal nanoemulsion-adjuvanted hsv-2 subunit vaccine is effective as a prophylactic and therapeutic vaccine using the guinea pig model of genital herpes.genital herpes is a sexually transmitted disease representing a major global health concern. currently, there is no approved vaccine and existing antiviral therapies exhibit limited efficacy. herein, we describe an intranasal (in) vaccine comprised of hsv-2 surface glycoproteins gd2 and gb2 formulated in a nanoemulsion adjuvant (ne01-gd2/gb2). using the hsv-2 genital herpes guinea pig model, we demonstrate that in ne01-gd2/gb2 induces higher levels of neutralizing antibody compared to a monovale ...201931515143
construction and characterization of the mycobacterium tuberculosis sige fadd26 unmarked double mutant as a vaccine candidate.despite the great increase in the understanding of the biology and pathogenesis of mycobacterium tuberculosis achieved by the scientific community in recent decades, tuberculosis (tb) still represents one of the major threats to global human health. the only available vaccine (mycobacterium bovis bcg) protects children from disseminated forms of tb but does not effectively protect adults from the respiratory form of the disease, making the development of new and more-efficacious vaccines against ...201931591165
an lcms-based untargeted metabolomics protocol for cochlear perilymph: highlighting metabolic effects of hydrogen gas on the inner ear of noise exposed guinea pigs.noise-induced hearing loss (nihl) is an increasing problem in society and accounts for a third of all cases of acquired hearing loss. nihl is caused by formation of reactive oxygen species (ros) in the cochlea causing oxidative stress. hydrogen gas (h2) can alleviate the damage caused by oxidative stress and can be easily administered through inhalation.201931587113
outer hair cell electromotility is low-pass filtered relative to the molecular conformational changes that produce nonlinear capacitance.the outer hair cell (ohc) of the organ of corti underlies a process that enhances hearing, termed cochlear amplification. the cell possesses a unique voltage-sensing protein, prestin, that changes conformation to cause cell length changes, a process termed electromotility (em). the prestin voltage sensor generates a capacitance that is both voltage- and frequency-dependent, peaking at a characteristic membrane voltage (vh), which can be greater than the linear capacitance of the ohc. accordingly ...201931676485
identification of bartonella rochalimae in guinea pigs (cavia porcellus) and fleas collected from rural peruvian households.in the present study, we tested 391 fleas collected from guinea pigs (cavia porcellus) (241 pulex species, 110 ctenocephalides felis, and 40 tiamastus cavicola) and 194 fleas collected from human bedding and clothing (142 pulex species, 43 c. felis, five t. cavicola, and four ctenocephalides canis) for the presence of bartonella dna. we also tested 83 blood spots collected on flinders technology associates (fta) cards from guinea pigs inhabiting 338 peruvian households. bartonella dna was detect ...201931674296
nucleoside-modified mrna encoding hsv-2 glycoproteins c, d, and e prevents clinical and subclinical genital herpes.the goals of a genital herpes vaccine are to prevent painful genital lesions and reduce or eliminate subclinical infection that risks transmission to partners and newborns. we evaluated a trivalent glycoprotein vaccine containing herpes simplex virus type 2 (hsv-2) entry molecule glycoprotein d (gd2) and two immune evasion molecules: glycoprotein c (gc2), which binds complement c3b, and glycoprotein e (ge2), which blocks immunoglobulin g (igg) fc activities. the trivalent vaccine was administere ...201931541030
mechanisms of electrical remodeling in lipotoxic guinea pig heart.to develop an adult guinea pig model of lipotoxicity and explore the underlying mechanisms associated with changes in the expression of the delayed rectifier potassium current (ik).201931540694
a 3d microscaffold cochlear electrode array for steroid elution.in cochlear implants, the electrode insertion trauma during surgery can cause damage residual hearing. preserving the residual hearing is an important challenge and the localized administration of drugs, such as steroids, is one of the most promising ways, but remains a challenge. here, a microscaffold cochlear electrode array (miscea) consisting of a microfabricated flexible electrode array and a 3d microscaffold for steroid reservoir is reported. the miscea without loaded drug is tested by mea ...201931532887
basal sodium-dependent vitamin c transporter 2 polarization in choroid plexus explant cells in normal or scorbutic conditions.vitamin c is incorporated into the cerebrospinal fluid (csf) through choroid plexus cells. while the transfer of vitamin c from the blood to the brain has been studied functionally, the vitamin c transporter, svct2, has not been detected in the basolateral membrane of choroid plexus cells. furthermore, it is unknown how its expression is induced in the developing brain and modulated in scurvy conditions. we concluded that svct2 is intensely expressed in the second half of embryonic brain develop ...201931594969
the way wear goes: phytolith-based wear on the dentine-enamel system in guinea pigs (cavia porcellus).the effect of phytoliths on tooth wear and function has been contested in studies of animal-plant interactions. for herbivores whose occlusal chewing surface consists of enamel ridges and dentine tissue, the phytoliths might particularly erode the softer dentine, exposing the enamel ridges to different occlusal forces and thus contributing to enamel wear. to test this hypothesis, we fed guinea pigs (cavia porcellus; n = 36 in six groups) for three weeks exclusively on dry or fresh forage of low ...201931594498
expression of cd63 in lung tissue of guinea pigs dying of anaphylactic shock.objective to study the protein expression of cluster of differentiation 63 （cd63） in lung tissues of guinea pigs that died of anaphylactic shock and discuss the diagnostic value of cd63 for death from anaphylactic shock. methods twenty guinea pigs were randomly divided into control group, anaphylactic shock immediate death group, cold storage group （4 ℃ for 48 h） and frozen group （-20 ℃ for 7 d）. the animal model of guinea pigs that died of anaphylactic shock was established with human mixed ser ...201931532145
anti-asthma effect of an active components group from decoction of pheretima aspergillum and its chemical composition characterized by liquid chromatography-quadrupole time of flight mass spectrometry.the decoction of pheretima aspergillum is used as a traditional medicine for treatment of asthma in china with a long clinical history. the aim of the study was to investigate the anti-asthma activities of an active components group obtained from the decoction of pheretima aspergillum in histamine and ovalubumin induced asthma guinea pigs. the experimental asthma model was established with spray of histamine and ovalbumin (ova) followed by intragastric administration of pheretima aspergillum ext ...201931531069
intermediate filaments in the retinal müller cells as natural light energy guides.in the current study, we investigated transmission spectrum of the intermediate filaments (ifs) extracted from porcine retinal müller cells (mc). the recorded transmission spectrum is quite similar to that of the entire guinea pig retina, providing direct proof that the quantum mechanism (qm) of light energy transmission through the inverted retina is in fact the main mechanism determining the high-contrast vision of the vertebrate eyes. the recorded transmission spectrum of the ifs was deconvol ...201931677421
synthesis, purification, and selective β2-ar agonist and bronchodilatory effects of catecholic tetrahydroisoquinolines from portulaca oleracea.a green, biomimetic, phosphate-mediated pictet-spengler reaction was used in the synthesis of three catecholic tetrahydroisoquinolines, 1, 2, and 12, present in the medicinal plant portulaca oleracea, as well as their analogues 3-11, 13, and 14, with dopamine hydrochloride and aldehydes as the substrates. ab-8 macroporous resin column chromatography was applied for purification of the products from the one-step high-efficacy synthesis. it eliminated the difficulties in the isolation of catecholi ...201931625751
alteration of musashi1 intra-cellular distribution during regeneration following gentamicin-induced hair cell loss in the guinea pig crista ampullaris.the mechanism underlying hair cell (hc) regeneration in the mammalian inner ear is still under debate. understanding what molecules regulate the hc regeneration in mature mammals will be the key to the treatment of the inner ear disorder. musashi1 (msi1) is an rna binding protein associated with asymmetric division and maintenance of stem cell function as a modulator of the notch-1 signaling pathway. in this study, we investigated the cellular proliferative activity and changes in spatiotemporal ...201931708751
the effects of high lighting on the development of form-deprivation myopia in guinea pigs.to investigate the effects of high ambient lighting on refraction and ocular biometry in guinea pig models of form-deprivation myopia (fdm).201931622468
tuberculin ppd potency assays in naturally infected tuberculous cattle as a quality control measure in the irish bovine tuberculosis eradication programme.the irish bovine tuberculosis (btb) eradication programme operates under national legislation and fulfills oie and eu trade requirements. tuberculin purified protein derivative (ppd), a preparation obtained from the heat-treated products of growth and lysis of mycobacterium bovis or mycobacterium avium (as appropriate), is critical to the diagnosis of tuberculosis (tb). standardization of tuberculin ppd potency, the relative activity in sensitized animals compared to a reference standard, is ess ...201931632988
formulation and evaluation of multilamellar vesicles ropivacaine in pain management.the improvement of postoperative pain control plays an important role in recovery outcomes and patient satisfaction. multilamellar vesicles ropivacaine, mvr, is being developed to sustain the release of ropivacaine in situ while maintaining the local concentration of ropivacaine within the therapeutic window.201931632006
central oxytocin alters cortisol and behavioral responses of guinea pig pups during isolation in a novel environment.the neuropeptide oxytocin plays key roles in social bonding and stress reduction, and thus appears to be a likely mediator of maternal buffering of infant stress responses. in the guinea pig, the presence of the mother in a threatening environment buffers cortisol elevations as well as active (vocalizing) and passive (e.g. crouching) responses typical of isolation in this species; yet, effects of ot in guinea pig pups under any conditions have not been reported. here, we examined the ability of ...201931629763
long-term effects and potential limits of intratympanic dexamethasone-loaded hydrogels combined with dexamethasone-eluting cochlear electrodes in a low-insertion trauma guinea pig model.cochlear implantation has become the most effective hearing restoration method and is one of the great advances in modern medicine. early implants have been continuously developed into more efficient devices, and electro-acoustic stimulation is increasingly expanding the indication criteria for cochlear implants to patients with more residual hearing. therefore, protecting the cochlear structures and maintaining its intrinsic capacities like residual hearing has become more important than ever b ...201931669876
attenuating effects of mangifera indica leaves ethanolic extract against acetamiprid induced reproductive toxicity in male guinea pigs.acetamiprid (acp) belonging to the neonicotinoid family used against wide array of pests in agriculture and domestic purposes. in this study, we evaluated the attenuating effects of ethanolic extract of mangifera indica leaves (eemi) in averting reproductive toxicity caused by acp in male guinea pigs. thirty male guinea pigs were randomly assigned to five treatment groups (n = 6). group 1 (t0) received distilled water orally; group 2 (t0-) was given 80 mg kg-1 of acp and groups 3, 4 and 5 were t ...201931737226
cardiac pacemaker cells generate cardiomyocytes from fibroblasts in long-term cultures.because cardiomyocyte generation is limited, the turnover of cardiomyocytes in adult heart tissues is much debated. we report here that cardiac pacemaker cells can generate cardiomyocytes from fibroblasts in vitro. sinoatrial node cells (sancs) were isolated from adult guinea pig hearts and were cultured at relatively low cell densities. within a week, a number of fibroblast-like cells were observed to gather around sancs, and these formed spontaneously beating clusters with cardiomyocyte struct ...201931645588
a case of a malignant peripheral nerve sheath tumor in a guinea pig.here, we describe the clinical and histopathological characteristics of a malignant peripheral nerve sheath tumor (mpnst) extending from the dorsal subcutis to the periphery of the spine in a female guinea pig aged 3 years 7 months. the patient presented with pleural and blood-like pericardial effusion and died. the tumor had invaded the spine and the surrounding muscles and had grown in hypercellular and hypocellular arrangements of round, broad-spindle, and elongated-spindle cells. we observed ...201931645521
differential modulation of ik and ica,l channels in high-fat diet-induced obese guinea pig atria.obesity mechanisms that make atrial tissue vulnerable to arrhythmia are poorly understood. voltage-dependent potassium (ik , ikur , and ik1 ) and l-type calcium currents (ica,l ) are electrically relevant and represent key substrates for modulation in obesity. we investigated whether electrical remodeling produced by high-fat diet (hfd) alone or in concert with acute atrial stimulation were different. electrophysiology was used to assess atrial electrical function after short-term hfd-feeding in ...201931607952
preparation and in vivo evaluation of a highly skin- and nail-permeable efinaconazole topical formulation for enhanced treatment of onychomycosis.onychomycosis is a progressive fungal infection of the nails that involves the deeper nail layer and nail bed. it is important to maintain sufficient drug concentration in the diseased tissues after topical application. in this study, a stable topical delivery system for efinaconazole (efn) was designed to enhance absorption potential through the skin and nail plate by incorporating ethanol, diethylene glycol monoethyl ether (transcutol p) and isopropyl myristate, and cyclomethicone into the top ...201931738083
author correction: histology, immunohistochemistry, and in situ hybridization reveal overlooked ebola virus target tissues in the ebola virus disease guinea pig model.an amendment to this paper has been published and can be accessed via a link at the top of the paper.201931611661
non-specific detection of a major western blotting band in human brain homogenates by a multitude of amyloid precursor protein antibodies.the use of human post-mortem brain material is of great value when investigating which pathological mechanisms occur in human brain, and to avoid translational problems which have for example been evident when translating animal research into alzheimer disease (ad) clinical trials. the amyloid β (aβ)-peptide, its amyloid precursor protein (app) and the intermediate app-c-terminal fragments (app-ctfs) are all important players in ad pathogenesis. in order to elucidate which app ctf that are the m ...201931649526
atorvastatin and vitamin e accelerates nash resolution by dietary intervention in a preclinical guinea pig model.despite affecting millions of patients worldwide, no pharmacological treatment has yet proved effective against non-alcoholic steatohepatitis (nash) induced liver fibrosis. current guidelines recommend lifestyle modifications including reductions in dietary energy intake. recently, therapy with atorvastatin and vitamin e (vite) has been recommended, although clinical studies on the resolution of hepatic fibrosis are inconclusive. targeting nash-induced hepatic end-points, this study evaluated th ...201931752351
enhanced triacylglycerol content and gene expression for triacylglycerol metabolism, acyl-ceramide synthesis, and corneocyte lipid formation in the epidermis of borage oil fed guinea pigs.triacylglycerol (tag) metabolism is related to the acyl-ceramide (cer) synthesis and corneocyte lipid envelope (cle) formation involved in maintaining the epidermal barrier. prompted by the recovery of a disrupted epidermal barrier with dietary borage oil (bo: 40.9% linoleic acid (lna) and 24.0% γ-linolenic acid (gla)) in essential fatty acid (efa) deficiency, lipidomic and transcriptome analyses and subsequent quantitative rt-pcr were performed to determine the effects of borage oil (bo) on tag ...201931752143
cardiac safety assessment with motion field imaging analysis of human ips cell-derived cardiomyocytes is improved by an integrated evaluation with cardiac ion channel profiling.we validated a motion field imaging (mfi) assay with human induced pluripotent stem cell-derived cardiomyocytes (hips-cms) as a model to assess multiple cardiac liabilities by comparing the guinea-pig langendorff heart with hips-cms using 4 reference compounds and 9 internal compounds. we investigated repolarization duration, beating rate (br), conduction speed, contractility, and inhibitory profile of three cardiac ion channels: herg, cav1.2, and nav1.5. for repolarization, the contraction-rela ...201931813905
ghrelin attenuates neuroinflammation and demyelination in experimental autoimmune encephalomyelitis involving nlrp3 inflammasome signaling pathway and pyroptosis.multiple sclerosis (ms) is a chronic autoimmune and degenerative disease of the central nervous system, and conventional treatments have limited efficacy or side effects. ghrelin, a 28-amino acid octanoylated peptide, has been reported to have neuroprotective effects, including anti-oxidation, anti-inflammation, and anti-apoptosis. pyroptosis, also called inflammatory cell death, is triggered by overly active inflammasomes and accompanied by the production of numerous cytokines. as immune dysfun ...201931780940
development of a diagnostic compatible bcg vaccine against bovine tuberculosis.bovine tuberculosis (btb) caused by mycobacterium bovis remains a major problem in both the developed and developing countries. control of btb in the uk is carried out by test and slaughter of infected animals, based primarily on the tuberculin skin test (ppd). vaccination with the attenuated strain of the m. bovis pathogen, bcg, is not used to control bovine tuberculosis in cattle at present, due to its variable efficacy and because it interferes with the ppd test. diagnostic tests capable of d ...201931780694
expression of adenosine receptors in rodent pancreas.adenosine regulates exocrine and endocrine secretions in the pancreas. adenosine is considered to play a role in acini-to-duct signaling in the exocrine pancreas. to identify the molecular basis of functional adenosine receptors in the exocrine pancreas, immunohistochemical analysis was performed in the rat, mouse, and guinea pig pancreas, and the secretory rate and concentration of hco3- in pancreatic juice from the rat pancreas were measured. the a2a adenosine receptor colocalized with ezrin, ...201931717704
electropharmacological profile of an atrial-selective sodium channel blocker acehytisine assessed in the isoflurane-anesthetized guinea-pig model.experimental evidence regarding the risk of proarrhythmic potential of acehytisine is limited. we assessed its electropharmacological effect together with proarrhythmic potential at intravenous doses of 4 and 10 mg/kg (n = 6) using isoflurane-anesthetized guinea pigs in comparison with that of bepridil at 1 and 3 mg/kg, intravenously (n = 6). acehytisine at therapeutic dose (4 mg/kg) decreased the heart rate, prolonged p wave duration, qrs width, qt interval, qtc, map90(sinus), map90(cl300) and ...201931757741
hematologic parameters and blood cultures from the gingival vein compared with the cranial vena cava in guinea pigs.blood collection methods in guinea pigs are limited due to the animals' compact neck, short limbs, and lack of a tail. gingival venipuncture is a recently described blood sampling technique that is minimally traumatic with no significant alterations in hematologic parameters when multiple blood samples were collected weekly for 6 wk. the purpose of this study was to determine whether the gingival vein can be used as an alternative blood collection site in guinea pigs, such that: (1) hematologic ...201931662155
[effect of arterial hypertension and hyperlipidemia on remodeling of articular cartilage and the development of osteoarthritis (experimental study).]osteoarthritis (oa) is a degenerative-inflammatory disease of the synovial joints associated with age, cardiovascular comorbidity, and other factors, based on cartilage (ac) and subchondral bone (scb) damage. recent studies have shown that age-related changes, cardiovascular diseases and oa may have a number of common molecular mechanisms. at the same time, the conditions and the degree of influence of arterial hypertension (ah) and hyperlipidemia (hl) on the tissues of the joints remain unclear ...201931800183
[changes of bk(ca) on vascular striaepericytes of d-galactose-induced aging model in guinea pigs].objective: the aging model of guinea pigs induced by d-galactose was set up to investigate the changes of bk(ca) expression and function on cochlear pericytes and their relationship with age-related hearing loss. methods: thirty healthy 8-week-old guinea pigs were randomly divided into three groups, with 10 in each group: d-galactose aging model group, subcutaneous injection of d-galactose (500 mg/kg) daily for 6 weeks; saline control group, the same amount of saline was injected into the neck o ...201931795546
comparative anatomy of the mammalian corneal subbasal nerve plexus.the subbasal nerve plexus (snp) is the densest and most recognizable component of the mammalian corneal innervation; however, the anatomical configuration of the snp in most animal models remains incompletely described. the purpose of the current study is to describe in detail the snp architecture in eight different mammals, including several popular animal models used in cornea research.201931790560
extended cleavage specificities of rabbit and guinea pig mast cell chymases: two highly specific leu-ases.serine proteases constitute the major protein content of mast cell (mc) secretory granules. these proteases can generally be subdivided into chymases and tryptases based on their primary cleavage specificity. here, we presented the extended cleavage specificities of a rabbit β-chymase and a guinea pig α-chymase. analyses by phage display screening and a panel of recombinant substrates showed a marked similarity in catalytic activity between the enzymes, both being strict leu-ases (cleaving on th ...201931888202
clinical management of pain in rodents.the use of effective regimens for mitigating pain remain underutilized in research rodents despite the general acceptance of both the ethical imperative and regulatory requirements intended to maximize animal welfare. factors contributing to this gap between the need for and the actual use of analgesia include lack of sufficient evidence-based data on effective regimens, under-dosing due to labor required to dose analgesics at appropriate intervals, concerns that the use of analgesics may impact ...201931822323
mva-vectored pentameric complex (pc) and gb vaccines improve pregnancy outcome after guinea pig cmv challenge, but only gb vaccine reduces vertical transmission.(1) background: a congenital cytomegalovirus (ccmv) vaccine is a major research priority, but the essential glycoprotein target(s) remain unclear. we compared cmv gb (gpgb), gh/gl (gp75/gl), and pentameric complex (gppc, composed of gh/gl/gp129/gp131/gp133) vaccines in a guinea pig cmv (gpcmv) congenital infection model. (2) methods: modified vaccinia virus ankara (mva) vaccines expressing gpcmv glycoproteins were used to immunize gpcmv-seronegative, female hartley guinea pigs (three-dose series ...201931739399
prenatal glucocorticoid exposure results in changes in gene transcription and dna methylation in the female juvenile guinea pig hippocampus across three generations.synthetic glucocorticoids (sgc) are administered to women at risk for pre-term delivery, to mature the fetal lung and decrease neonatal morbidity. sgc also profoundly affect the fetal brain. the hippocampus expresses high levels of glucocorticoid (gr) and mineralocorticoid receptor (mr), and its development is affected by elevated fetal glucocorticoid levels. antenatal sgc results in neuroendocrine and behavioral changes that persist in three generations of female guinea pig offspring of the pat ...201931796763
otoprotection to implanted cochlea exposed to noise trauma with dexamethasone eluting electrode.cochlear implantation (ci) is now widely used to provide auditory rehabilitation to individuals having severe to profound sensorineural hearing loss (snhl). however, ci can lead to electrode insertion trauma (eit) that can cause damage to sensory cells in the inner ear resulting in loss of residual hearing. even with soft surgical techniques where there is minimal macroscopic damage, we can still observe the generation of molecular events that may initiate programmed cell death via various mecha ...201931824265
[18f]spa-rq/pet study of nk1 receptors in the whole body of guinea pig and rat.there is a substantial interest in the development of nk1 substance p antagonists as potential treatments for various neuropsychiatric and somatic disorders. the aim of this study was to determine whether [18f]spa-rq can be utilized as a tool for studying the whole body distribution and function of nk1 receptors in preclinical settings. the compound was injected into guinea pigs with or without premedication with a nk1 receptor antagonist (nk1a-2). for comparison, we included two rats in the stu ...201931892711
pharmacological basis for the medicinal use of alcea rosea in airways disorders and chemical characterization of its fixed oils through gc-ms.alcea rosea l. also known as althea rosea belongs to the malvaceae family. this medicinal herb, traditionally used to treat several conditions including airway disorders like asthma and chronic bronchitis. this study evaluated the bronchodilatory effects and possible mechanism of a. rosea on guinea-pig tracheal tissues. moreover lipophilic profiling of a. rosea has been carried out by using gas-chromatography-mass-spectrometry. a total of 19 compounds have been identified from the plant, n-hexan ...201931894065
evaluation of prokinetic and laxative effects of hippophae rhamnoides in rodents.hippophae rhamnoides (family; elaeagnaceae) fruit extract was investigated for prokinetic and gut excitatory effects to rationalize its therapeutic utility in gastrointestinal complaints like delayed gastric emptying and constipation. the fruit extract of hippophae rhamnoides (hr.cr) prepared in hydro-methanol (30:70) was verified for flavonoids, tannins, coumarins and terpenes as plant constituents. in mice, hr.cr administration caused an increased in faecal production and charcoal meal transpo ...201931894044
altered pulmonary capillary permeability in immunosuppressed guinea pigs infected with legionella pneumophila serogroup 1.in immunosuppressed hosts, legionella pneumophila (lp) infection usually develops into severe pneumonia, which is pathologically characterized by increased vascular permeability and pulmonary edema. at present, mechanisms associated with changes in pulmonary capillary permeability (pcp) and the pathogenesis of pulmonary edema in immunosuppressed hosts with lp infection are unclear. therefore, in the present study an animal model of normal and immunosuppressed guinea pigs infected with lp was est ...201931772633
animal models of type iii secretion system-mediated pathogenesis.the type iii secretion system (t3ss) is a conserved virulence factor used by many gram-negative pathogenic bacteria and has become an important target for anti-virulence drugs. most t3ss inhibitors to date have been discovered using in vitro screening assays. pharmacokinetics and other important characteristics of pharmaceuticals cannot be determined with in vitro assays alone. in vivo assays are required to study pathogens in their natural environment and are an important step in the developmen ...201931766664
pioglitazone prevents cholesterol gallstone formation through the regulation of cholesterol homeostasis in guinea pigs with a lithogenic diet.the cholesterol gallstones diseases (cgd) is highly correlated with metabolic syndrome and type 2 diabetes. the present study aimed to investigate preventive effects of pioglitazone (pio), an antidiabetic drug, on the cgd in guinea pigs fed with a lithogenic diet (ld).201931829191
high reproductive success despite queuing - socio-sexual development of males in a complex social environment.the start of actual breeding in male social mammals can occur long after individuals attain sexual maturity. mainly prevented from reproduction by older and dominant males, young males often queue until strong enough to compete for favorable social positions and, in this way, to obtain access to females. however, to what extent maturing males also apply tactics to reproduce before this time is largely unknown. therefore, the aim of the present study was to elucidate male socio-sexual development ...201931920852
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