Complete Reversal Research Articles

Breaking Osteoclast-Acid Vicious Cycle to Rescue Osteoporosis via an Acid Responsive Organic Framework-Based Neutralizing and Gene Editing Platform.

In the osteoporotic microenvironment, the acidic microenvironment generated by excessive osteoclasts not only causes irreversible bone mineral dissolution, but also promotes reactive oxygen species (ROS) production to induce osteoblast senescence and excessive receptor activator of nuclear factor kappa-B ligand (RANKL) production, which help to generate more osteoclasts. Hence, targeting the acidic microenvironment and RANKL production may break this vicious cycle to rescue osteoporosis. To achieve this, an acid-responsive and neutralizing system with high in vivo gene editing capacity is developed by loading sodium bicarbonate (NaHCO3) and RANKL-CRISPR/Cas9(RC) plasmid in a metal-organic framework. This results showed ZIF8-NaHCO3@Cas9 (ZNC) effective neutralized acidic microenvironment and inhibited ROS production . Surprisingly, nanoparticles loaded with NaHCO3 and plasmids show higher transfection efficiency in the acidic environments as compared to the ones loaded with plasmid only. Finally, micro-CT proves complete reversal of bone volume in ovariectomized mice after ZNC injection into the bone remodeling site. Overall, the newly developed nanoparticles show strong effect in neutralizing the acidic microenvironment to achieve bone protection through promoting osteogenesis and inhibiting osteolysis in a bidirectional manner. This study provides new insights into the treatment of osteoporosis for biomedical and clinical therapies.

Homeopathic potencies can regulate the growth and toxicity of Raphidiopsis raciborskii (cyanobacteria) and are traceably by solvatochromic dyes

Introduction: Cyanobacteria are found worldwide and can produce cyanotoxins. Since homeopathic potencies can modulate toxicity in different biological models, this study proposes to investigate whether cyanobacteria toxins might also be the case. Objectives: a) to investigate if homeopathic potencies can improve the resilience of Artemia franciscana (brine shrimp) embryos to saxitoxin (cyanotoxin) and to control the growth of Raphidiopsis raciborskii in vitro; b) to verify if physicochemical parameters can be used to track homeopathic potencies in seawater or cyanobacteria medium, with special focus on the interaction with solvatochromic dyes. Method: Artemia franciscana cysts were cultivated in seawater in 96-well plates to evaluate the hatching rate, vitality, and gene expression of heat shock proteins (Hsp), after being challenged with R. raciborskii extract containing 2.5 µg/liter of saxitoxin and treated with different homeopathic potencies chosen from a screening process. Cultures of R. raciborskii maintained in ASM-1 medium were equally treated with previously screened homeopathic potencies, and their growth was monitored as a function of time. The physicochemical properties of treated water were evaluated by interacting with solvatochromic dyes and measuring pH, conductivity, and temperature. Results: A lower rate of hatching of Artemia franciscana cysts was observed after treatment with Nitric acidum 6cH (p=0.03), and a complete toxicity reversal with increased Hsp 26 and p26 gene expression was seen after treatment with Isotherapic (R. raciborskii extract) 200cH (p≤0.02). Nitric acidum 200cH and Mercurius solubilis 30cH limited the exponential growth of cyanobacteria (p≤0.003) regardless of their concentration. Coumarin 7 was a marker for Nitric acidum 6cH and Isotherapic (R. raciborskii extract) 200cH, even when inserted into seawater. Nile red was a marker for Nitric acidum 200cH and Mercurius solubilis 30cH, even when inserted into ASM-1 medium (p≤0.05). An increase in pH and endo/exothermal effects of the ASM-1 medium was observed after these treatments (p≤0.007). The physicochemical analyzes were optimized after the previous submission of the samples to a constant unidirectional 2400 Gauss magnetic flow. Conclusion: The Isotherapic 200cH improved Artemia franciscana bioresilience to saxitoxin itself; Nitric acidum 200cH and Mercurius solubilis 30cH limited the growth of R. raciborskii. In all cases, those homeopathic potencies that showed biological effects were traceable in the aqueous medium using solvatochromic dyes, especially when the samples were subjected to the magnetic field.

Fully Recyclable Cured Polymers for Sustainable 3D Printing.

The most prevalent materials used in the Additive Manufacturing era are polymers and plastics. Unfortunately, these materials are recognized for their negative environmental impact as they are primarily nonrecyclable, resulting in environmental pollution. In recent years, a new sustainable alternative to these materials has been emerging: Reversible Covalent Bond-Containing Polymers (RCBPs). These materials can be recycled, reprocessed, and reused multiple times without losing their properties. Nonetheless, they have two significant drawbacks when used in 3D printing. First, some require adding new materials every reprinting cycle, and second, others require high temperatures for (re)printing, limiting recyclability, and increasing energy consumption. This study, thus, introduces fully recyclable RCBPs as a sustainable approach for radiation-based printing technologies. This approach enables multiple (re)printing cycles at low temperatures (50°C lower than the lowest reported) without adding new materials. It involves purposefully synthesized polymers that undergo reversible photopolymerization, composed of a tin-based catalyst. An everyday microwave oven quickly depolymerized these polymers, obtaining complete reversibility.

2559. Antibiotic-induced Bartter-like syndrome - A Systematic Review

Abstract Background Bartter syndrome encompasses salt-losing tubulopathies characterized by hypokalemia, hypochloremic metabolic alkalosis, and hyperreninemic hyperaldosteronism with normal blood pressure. Acquired Bartter or Bartter-like syndrome (BLS) is commonly associated with the use of diuretics and antibiotics such as capreomycin, netilmicin, colistin, and amphotericin B. This systematic review was done to understand the time of occurrence of Bartter syndrome post-inciting drug and gain knowledge regarding its progression and management. Methods We searched PubMed, Google Scholar, Embase, medRxiv, and bioRxiv databases for articles published from 1986 to March 2022 using the keywords "Antibiotic," "Bartter Syndrome," "Pseudobartter Syndrome," and "Bartter-like." Studies that reported cases of BLS in adults or children with confirmation of the inciting drug were included. We excluded studies that did not provide sufficient details of the clinical presentation and outcome. Results We identified 31 studies, comprising 43 cases of BLS. The mean age of the patients was 41.1 years (range: 25–57 years), and 65.1% were female. The most common antimicrobial class associated with BLS was aminoglycosides (65.1%), followed by the polymyxin group. The most common antimicrobial was Gentamicin (41.8%), followed by Colistin (32.5%), Streptomycin, and Capreomycin (6.9% each). Hypokalemia(100%), metabolic alkalosis(97.2%), hypocalcemia(92.5%), and hypomagnesemia(100%) were reported in almost all patients. The median time of onset after exposure to the inciting agent was 10 days (range 7–18 days), and the median time for resolution after stopping the drug was 14 days (range 7–31 days). There was a complete resolution of the symptoms following discontinuation in all cases. Demographic and baseline characteristics of the patients Prevalence of electrolyte, acid-base disorder, and urinary electrolyte abnormalities Laboratory parameters among the reported cases Conclusion BLS is a rare but potentially reversible complication of various antimicrobials, most commonly aminoglycosides. The diagnosis requires a high index of suspicion and a careful review of the drug history. The prognosis is favorable, with a complete reversal of the state after drug discontinuation. Disclosures All Authors: No reported disclosures

Brain functional segregation, handedness and cognition in situs inversus totalis: A replication study

Situs inversus totalis (SIT) is a rare congenital anomaly in which the arrangement of the visceral organs is completely left-right mirrored. A previous study by our lab suggests that SIT (N = 15) correlated with more heterogeneous asymmetrical brain organization and increased left-handedness. In addition, visceral reversal correlated with poorer cognitive performance, especially when hemisphere organization was atypical. The current study sought to replicate these findings in a larger sample. We scanned 23 volunteers with SIT as well as an equal number of controls with usual organ arrangement, and used fMRI to determine their hemisphere dominance for two left hemisphere functions (language and manual praxis) and two right hemisphere functions (spatial attention and face recognition). Effects of SIT etiology were explored by pooling data from the original cohort with the replication sample. Our results reveal that each of those four cognitive functions demonstrated the expected population dominance in SIT, albeit they were less pronounced – but not significantly so – compared to controls. Unusual patterns of hemispheric crowding and mirror-reversal of functional brain organization was observed more often in SIT (48%) than in the controls (30%), but this difference also did not reach statistical significance. However, left-handedness was found to be significantly more common in SIT (26%) than in the overall population (10.6%). Finally, cognitive ability, as assessed by a neuropsychological test battery, was not associated with organ situs or hemisphere organization. Taken together, our data adds to the growing evidence that the determinants of visceral and neural asymmetries are largely independent from one another and that complete situs inversus does not co-occur with an obligatory transposition of the brain's functional architecture. There nevertheless might be instances in which (genetic) mechanisms could simultaneously cause complete visceral reversal and atypical brain laterality.

High capacity reversible data hiding with contiguous space in encrypted images

Reversible data hiding in encrypted images (RDHEI) is used to embed secret data into an encrypted image to ensure data security and image privacy. However, a considerable portion of the existing methods do not achieve a high data embedding rate (ER) with complete reconstruction of the original image. Considering the aforementioned limitation, this paper proposes a new RDHEI method with contiguous space. The proposed method pre-processes the original image by dividing it into non-overlapping blocks to determine a label map based on absolute prediction errors. Next, the label map is encoded, and bit-plane shifting is done to create contiguous space for embedding. Thus, the proposed method effectively exploits local and overall image spatial correlation and creates a larger space for embedding in a bit-plane-wise manner. Compared to the state-of-the-art methods, the ER of the proposed method is significantly increased while ensuring complete reversibility and lossless extraction of the hidden data.

Abstract 106: CHANTER Syndrome: A Case Report Of A 59 Year Old Man With Positive Outcome

Introduction Cerebellar, Hippocampal, and Basal Nuclei Transient Edema with Restricted Diffusion (CHANTER) syndrome was first described in 2019 [1] as a pattern of radiographic findings that are distinct from ischemic, anoxic, or toxic brain injury. Pathophysiology is still uncertain, but some proposed theories include a primary metabolic etiology or a mitochondrial failure of gray matter. Clinically, patients typically present with altered level of consciousness. Radiographically, diffusion weighted imaging shows restriction in the bilateral hippocampi, bilateral cerebelli, and basal nuclei. The cerebral cortex, thalamus, and subcortical white matter are usually spared. Despite the morbid clinical picture on presenation, positive outcomes were reported with early intervention. We describe a case of CHANTER syndrome in a 59 year old man with history of illicit substance abuse. Methods Case report with electronic medical record review. Results 59‐year‐old man with history of illicit substance abuse including cocaine, opioid, and phencyclidine presented to the hospital after being found down at a drug store. Patient did not respond to Naloxone and was eventually intubated due to respiratory compromise. Non‐contrast CT head showed hypoattenuation of the bilateral cerebellar hemispheres with mild effacement of the fourth ventricle. MRI brain showed diffusion signal abnormalities with corresponding T2 FLAIR hyperintensities in the bilateral cerebellar hemispheres, bilateral hippocampi, and bilateral basal ganglia with some involvement of the left occipital lobe suggestive of CHANTER syndrome. As vasogenic edema worsened, hydrocephalus ensued requiring administration of hypertonic saline and eventual external ventricular drain (EVD) insertion in the neurocritical care unit. Despite initial improvement in his level of consciousness after the EVD insertion, his intracranial pressure (ICP) continued to increase and midazolam and ketamine infusion drips were added. A fine balance between lowering the ICP and avoiding respiratory suppresion with sedating infusions was maintained. Consecutive MRI brain images over the course of the following 4 weeks of his stay showed decrease of the abnormal diffusion weighted imaging signal along with improvement in his overall mental status and eventual discharge 12 weeks from his initial presentation. Conclusion This case further strengthens the relationship between CHANTER syndrome and illicit substance use as a likely etiology along with other cases in the literature. Aggressive management in the neurocritical care to control vasogenic edema and avoid ICP elevation is essential to give patients the highest chance of recovery. Clinical improvement At least partial reversal of the radiographic findings of CHANTER syndrome can be attained with treatment, however, unclear if complete reversal is possible.

Reversible Data Hiding in Encrypted Images Based on Binary Symmetric Channel Model and Polar Code

For vacating-room-after-encryption reversible data hiding in encrypted images (VRAE RDHEI), an essential problem is how to address potential errors in data extraction and image recovery. This problem significantly limits the capacities of the existing VRAE RDHEI methods. To solve the problem while losing as little capacity as possible, in this paper, a novel method is proposed that uses the ideas of noisy channel model and channel code. By designing the data hiding mechanism appropriately, the embedding and extraction of data in the proposed method can be equivalent to the input and output of a virtual binary symmetric channel (BSC) model, so that the errors in data extraction are equivalent to the bit transitions in BSC. Based on the virtual BSC model, polar code is used to encode the secret data in the data hider's side. With the help of polar code, the receiver can decode the extracted bits containing errors to obtain correct secret data, then recover the error-free original image based on the corrected secret data. The experimental results proved that, compared with the existing VRAE methods, the proposed method can significantly improve the capacity and the quality of the decrypted images under the premise of complete reversibility.

OTHER-11 DEMENTIA AND EPILEPSY REVERSED SUCCESSFULLY THROUGH STAGED EMBOLISATION OF A SYMPTOMATIC HYPERVASCULAR PARAGANGLIOMA : A CASE REPORT

Abstract INTRODUCTION Paragangliomas (PGs) are rare neuroendocrine tumours that can arise from parasympathetic glossopharyngeal and vagus nerves. Atypical presentations involving seizures and dementia can occur due to excessive catecholamine release. Physiological intracranial arteriovenous fistulae (AVF) can occur concurrently due to increased vascularity, especially in the cavernous and sigmoid sinuses. METHODS We present a case of a patient who developed a highly vascular AVF from an ipsilateral glomus jugulare PG, presenting with rapidly progressive but reversible dementia and epilepsy. CASE: A 64-year-old lady presented on several occasions with new-onset stereotyped episodes of confusional dysphasia suggestive of seizures, confirmed on electroencephalography. Further history revealed two years of progressive deafness and imbalance, and one year of increasing forgetfulness and executive dysfunction, which had deteriorated rapidly in the period of the patient's current presentations. Montreal cognitive assessment (MoCA) score was 21/30 at baseline (normal score >25/30), and she had no lateralising signs. Serial brain magnetic resonance imaging (MRI) revealed progressively worsening vasculopathic white matter hyper-intensities (WMHs). Eventual MR angiography showed a 14x22×23mm right glomus jugulotympanicum PG with numerous feeding arteries, and associated multiple AVFs (Cognard grade III). She was initially managed with anti-seizure medications and then discussed in our multidisciplinary neurosciences meeting. The patient underwent staged right glomus jugulare embolization over several weeks. Her cognitive function gradually improved, and at three months she had fully returned to normal functioning with a MoCA of 30/30 and no residual neurological deficit. The WMHs disappeared on follow-up MRI scans. CONCLUSION Our case highlights a rare clinical presentation of dementia and seizures from a right glomus jugulare PG with associated AVF. Multidisciplinary involvement was key in excluding other causes, and definitive treatment of the PG led to complete reversal of the patient’s dementia.

The Link between Periodontal Disease and Asthma: How Do These Two Diseases Affect Each Other?

A growing body of evidence suggests that the effects of poor oral hygiene extend beyond the oral cavity and are associated with a variety of systemic diseases, including asthma. Asthma, which results in symptoms of cough, wheezing, and dyspnoea, and is characterized by airflow limitation with variability and (partial or complete) reversibility, is amongst the most prevalent respiratory diseases with approximately 262 million patients worldwide, and its prevalence and disease burden is on the increase. While asthma can occur at a young age, it can also develop later in life and affects a variety of age groups. Both of these diseases have a chronic course, and various researchers have suggested a link between the two. In this article, we aim to provide a literature review focusing on the association between the two diseases. The results demonstrate that medications (primarily, inhaler medicine), hypoxia induced by asthma, and the breathing behaviour of patients potentially trigger periodontal disease. In contrast, oral periodontopathogenic microorganisms and the inflammatory mediators produced by them may be involved in the onset and/or exacerbation of asthma. Common contributing factors, such as smoking, gastro-oesophageal reflux, and type-2 inflammation, should also be considered when evaluating the relationship between the two diseases.

Ophthalmic Atropine: A Typical Anticholinergic Toxidrome From an Atypical Old Culprit.

Included on the World Health Organization Model Lists of Essential Medicines, atropine remains a cornerstone medication that is used for a myriad of clinical indications. Systemically, atropine carries indications for the treatment of asymptomatic and symptomatic bradycardia, reduction of salivation and bronchial secretions prior to surgery, and as an antidote for a variety of poisoning agents (i.e., carbamate or organophosphate insecticides, nerve agents, muscarine-containing mushrooms). Topically, atropine is administered via the ophthalmic route for the treatment of cycloplegia, mydriasis, and amblyopia or may be administered sublingually to treat chronic sialorrhea. As an anticholinergic, supratherapeutic concentrations of atropine result in a toxidrome typical of other anticholinergic medication overdoses. However, it is easy to overlook atropine as the causative agent when being administered topically, potentially resulting in an unnecessarily extensive and complicated workup. This case report describes the systemic absorption of atropine administered through the ophthalmic route at normal doses, resulting in stroke-like symptoms in an adolescent male. Upon identifying that the patient was being treated with atropine ophthalmic drops prior to hospital arrival, a dose of intravenous physostigmine was administered, resulting in complete reversal of all toxidrome symptoms.

Celecoxib attenuates neuroinflammation, reactive astrogliosis and promotes neuroprotection in young rats with experimental hydrocephalus

Hydrocephalus is a neurological condition with altered cerebrospinal fluid flow (CSF). The treatment is surgical and the most commonly used procedure is ventricle-peritoneal shunt. However, not all patients can undergo immediate surgery or achieve complete lesion reversal. Neuroprotective measures are valuable in such cases. It was evaluated whether the use of celecoxib, a selective inhibitor of COX-2, associated or not with ventricular-subcutaneous derivation, could offer benefits to the brain structures affected by experimental hydrocephalus. Seven-day-old male Wistar Hannover rats induced by intracisternal injection of kaolin 15% were used, divided into five groups with ten animals each: intact control (C), untreated hydrocephalus (H), hydrocephalus treated with celecoxib 20 mg/kg intraperitoneal (HTC), hydrocephalus treated with shunt (HTS) and hydrocephalus treated with shunt and celecoxib 20 mg/kg intraperitoneal (HTCS). Celecoxib was administered for 21 consecutive days, starting the day after hydrocephalus induction and continuing until the end of the experimental period. The surgery was performed seven days after inducing hydrocephalus. Multiple assessment methods were used, such as behavioral tests (water maze and open field), histological analysis (hematoxylin and eosin), immunohistochemistry (caspase-3, COX-2, and GFAP), and ELISA analysis of GFAP. The results of the behavioral and memory tests indicated that celecoxib improves the neurobehavioral response. The improvement can be attributed to the reduced neuroinflammation (p < 0.05), and astrogliosis (p < 0.05) in different brain regions. In conclusion, the results suggest that celecoxib holds great potential as an adjuvant neuroprotective drug for the treatment of experimental hydrocephalus.

Optimization and evaluation of ultra-trace amounts of lead in real samples using sol–gel based optical sensor coupled with colorimetry

The entrapment of the sensitive reagent 5-(2′-bromophenylazo)-6‑hydroxy-pyrimidine-2,4‑dione (BPAHPD) in a silica sol-gel thin film coated on a glass substrate has been investigated for the development of a highly sensitive and selective optode for the determination of lead ions. The fabrication of thin films requires tetraethoxysilane as a precursor, a sol-gel pH of 2.75, a water: alkoxide ratio of 5:1, and a BPAHPD concentration of 4.0 × 10–4 M. The effect of sol-gel parameters on the optode's sensing performance was investigated. The fabricated optode is utilized for lead ion detection over a dynamic range of 4.00–144 ng mL–1 with detection and quantification limits of 1.20 and 3.95 ng mL–1, respectively. It gave repeatable results with relative standard deviation (RSD) values of 1.90% and 1.15% for lead concentrations of 40.0 and 80.0 ng mL–1, respectively, and a response time of two minutes. Through capturing BPAHPD in a sol-gel matrix and appropriately modifying the structure of doped sol-gel, interference studies have determined that lead exhibits a high degree of selectivity. To ascertain total lead, Pb4+ was reduced to Pb2+ using a few drops of 6.00 M hydrochloric acid and a freshly prepared sodium azide solution of 2.50 % (w/v). The optode can be easily regenerated with 0.15 M of nitric acid solution. The optode has complete reversibility. Optode detection of lead in diverse vegetable, food, biological, water, and soil samples yielded favorable results when compared to other techniques.

The Spinodal Decomposition of Ferrite in 2507 Biphasic Stainless Steels: Embrittlement and Possible Toughness Recovery

Biphasic stainless steels provide an excellent combination of mechanical and corrosion properties. The occurrence of ferrite spinodal decomposition during processing and heat treatment can induce a dramatic drop in impact energy. In this paper, a forged rod of 480 mm diameter made of 2507 biphasic stainless steel was studied. The spinodal decomposition phenomenon upon aging at 475 °C (748 K) was investigated by macro- and micro-hardness tests on the constituent phases and by Charpy impact tests. Then, the influence of the microstructural constituents and their morphology on the crack path was studied by optical microscopy, noting possible correlations with the impact energy. Successively, the fracture surfaces of selected specimens were analyzed by a scanning electron microscope (SEM). Finally, reversion heat treatments at 550 °C (823 K) and 600 °C (873 K) were investigated to evaluate the possibility of recovering the detrimental effects of the α′ embrittlement. According to the literature, this procedure works well with some biphasic steels, but these steels are characterized by a chromium content lower than that of 2507 grade steel. Regarding the 2507 grade steel studied in this work, complete reversion was obtained by solution-annealing treatment, while reversion heat treatments at both 600 °C (873 K) and 550 °C (823 K) allowed only a partial recovery.

Insulin-like Androgenic Gland Hormone Induced Sex Reversal and Molecular Pathways in Macrobrachium nipponense: Insights into Reproduction, Growth, and Sex Differentiation.

This study investigated the potential to use double-stranded RNA insulin-like androgenic gland hormone (dsIAG) to induce sex reversal in Macrobrachium nipponense and identified the molecular mechanisms underlying crustacean reproduction and sex differentiation. The study aimed to determine whether dsIAG could induce sex reversal in PL30-male M. nipponense during a critical period. The sex-related genes were selected by performing the gonadal transcriptome analysis of normal male (dsM), normal female (dsFM), neo-female sex-reversed individuals (dsRM), and unreversed males (dsNRM). After six injections, the experiment finally resulted in a 20% production of dsRM. Histologically, dsRM ovaries developed slower than dsFM, but dsNRM spermathecae developed normally. A total of 1718, 1069, and 255 differentially expressed genes were identified through transcriptome sequencing of the gonads in three comparison groups, revealing crucial genes related to reproduction and sex differentiation, such as GnRHR, VGR, SG, and LWS. Principal Component Analysis (PCA) also distinguished dsM and dsRM very well. In addition, this study predicted that the eyestalks and the "phototransduction-fly" photoperiodic pathways of M. nipponense could play an important role in sex reversal. The enrichment of related pathways and growth traits in dsNRM were combined to establish that IAG played a significant role in reproduction, growth regulation, and metabolism. Finally, complete sex reversal may depend on specific stimuli at critical periods. Overall, this study provides valuable findings for the IAG regulation of sex differentiation, reproduction, and growth of M. nipponense in establishing a monoculture.

The Contribution of Curable Plasmid-Mediated Resistance in Isolates of Staphylococcus aureus at the University of Benin Teaching Hospital, Benin City, Nigeria

aureus, is an important human pathogen and commensal that is responsible for infections ranging from minor to deep-seated life-threatening conditions. Multi-drug resistant S. aureus or MRSA is a major cause of hospital acquired infection (HAIs) or nosocomial infections with consequential reduction in treatment options and overtly increased cost of healthcare, morbidity and mortality. The study was conceived to determine the contribution of curable transmissible plasmids to the ever-increasing proportion of multi-drug resistant S. aureus at the University of Benin Teaching Hospital, Benin City. A total of 448 consecutive multi-drug resistant clinical isolates of S. aureus were collected, confirmed by SCT and TCT and resistance to commonly used antimicrobial agents. Each isolate was inoculated into Mueller-Hinton Broth containing 100 µg/mL acridine orange and incubated at 37oC for 24 h. Each broth culture was subsequently sub-cultured onto blood agar plates and incubated at 37oC for 24 h. Sensitivity tests were thereafter done on each sub-culture by the Kirby-Bauer disc diffusion method. SCT and TCT were re-tested on each sub-culture. Isolates with curable transmissible plasmids were 31/448(6.9%) and there was complete reversion to sensitivity in all the cured strains to antimicrobial agents tested including ampicillin. The remaining isolates (93.1%) retained their resistance to all the antimicrobial agents. The isolates with curable plasmids (6.9%) also lost the coagulase activity of both types. Plasmid-mediated resistance in S. aureus remain an important route of multi-drug resistance, however this is dwarfed by chromosomally-mediated resistance as the major mechanism of resistance in multi-drug resistance S. aureus. Additionally, the cure of drug resistance was also concomitantly associated with lose of the pathogenicity factor-coagulase in these isolates. Keywords: S. aureus, multi-drug resistance, transmissible plasmids.

Vanillin: An Effective Additive to Improve the Longevity of Zn Metal Anode in a 30 m ZnCl2 Electrolyte

AbstractIt remains a challenge to design aqueous electrolytes to secure the complete reversibility of zinc metal anodes. The concentrated water‐in‐salt electrolytes, e.g., 30 m ZnCl2, are promising candidates to address the challenges of the Zn metal anode. However, the pure 30 m ZnCl2 electrolyte fails to deliver a smooth surface morphology and a practically relevant Coulombic efficiency. Herein, it is reported that a small concentration of vanillin, 5 mg mLwater−1, added to 30 m ZnCl2 transforms the reversibility of Zn metal anode by eliminating dendrites, lowering the Hammett acidity, and forming an effective solid electrolyte interphase. The presence of vanillin in the electrolyte enables the Zn metal anode to exhibit a high Coulombic efficiency of 99.34% at a low current density of 0.2 mA cm−2, at which the impacts of the hydrogen evolution reaction are allowed to play out. Using this new electrolyte, a full cell Zn metal battery with an anode/cathode capacity (N/P) ratio of 2:1 demonstrates no capacity fading over 800 cycles.

Isolated Third Cranial Nerve Palsy Associated with Sudden Worsening of Hypotonic Hyponatremia Secondary to Ischemic Pituitary Apoplexy

Pituitary apoplexy (PA) is a rare medical emergency. The sudden pressure increase in the sella turcica may determine compression on the surrounding structures determining the classical symptomatology associated, especially visual field impairment and/or ocular palsies and hypopituitarism; hypotonic hyponatremia may occur too, even if it is not common. Although already described in the literature, cases of isolated III cranial nerve palsies are extremely rare events. We report the case of a mid-60-year-old man with a known pituitary adenoma accessing the Emergency Department (ED) for worsening headaches unresponsive to analgesics, with a morphological picture consistent with ischemic PA, despite no dimensional increase of the pituitary lesion; upon ED access, a mild paucisymptomatic hyponatremia was also observed. Dexamethasone and mannitol were empirically introduced upon neurosurgical indication and tramadol and ketorolac were promptly administered as well, but without benefit. In the next days, a severe hypotonic hyponatremia was evidenced and a clear left III cranial nerve palsy developed, but no clear signs of cerebral bleeding or ischemia, nor a significant compression on the homolateral cavernous sinus, were observed. Upon ruling out other possible causes, a likely diagnosis of syndrome of inappropriate antidiuresis (SIAD) was made, confirmed by the quick response to fluid restriction. Overall, the sudden fall in tonicity plasma levels seemed to contribute to the exacerbation of the neurological deficit since the normalization of sodium levels was associated with a rapid and complete reversion of the III cranial nerve palsy.

Role of Dielectric Drag in Circumventing the Solubility-Diffusivity Trade-off in Zwitterionic Copolymer Membranes.

Recent experiments have revealed that random zwitterionic amphiphilic copolymer (r-ZAC) membranes exhibit excellent Cl-/F- permselectivity circumventing the solubility-diffusivity trade-off. We conducted molecular dynamics simulations to investigate the origin of the experimental results on the transport of sodium halides in r-ZAC membranes. Our results indicate that the enhancement of Cl-/F- diffusivity selectivity in r-ZAC membranes (relative to that in bulk water) stems from the increase in dielectric drag dominating over the increase in Stokes drag, zwitterionic group-induced steric hindrance, and ion-polymer interactions. The importance of dielectric drag is further demonstrated by showing that reduction in ionic charges leads to a complete reversal of the diffusivity selectivity trends. We conclude that leveraging the impact of hydrophilic nanoconfinement on the dynamics of water can be utilized as a strategy to simultaneously augment solubility selectivity and diffusivity selectivity for separations, wherein the flux of the larger ionic species is desired over that of the smaller.

FoxO3 normalizes Smad3-induced arterial smooth muscle cell growth.

Transition of arterial smooth muscle (ASM) from a quiescent, contractile state to a growth-promoting state is a hallmark of cardiovascular disease (CVD), a leading cause of death and disability in the United States and worldwide. While many individual signals have been identified as important mechanisms in this phenotypic conversion, the combined impact of the transcription factors Smad3 and FoxO3 in ASM growth is not known. The purpose of this study was to determine that a coordinated, phosphorylation-specific relationship exists between Smad3 and FoxO3 in the control of ASM cell growth. Using a rat in vivo arterial injury model and rat primary ASM cell lysates and fractions, validated low and high serum in vitro models of respective quiescent and growth states, and adenoviral (Ad-) gene delivery for overexpression (OE) of individual and combined Smad3 and/or FoxO3, we hypothesized that FoxO3 can moderate Smad3-induced ASM cell growth. Key findings revealed unique cellular distribution of Smad3 and FoxO3 under growth conditions, with induction of both nuclear and cytosolic Smad3 yet primarily cytosolic FoxO3; Ad-Smad3 OE leading to cytosolic and nuclear expression of phosphorylated and total Smad3, with almost complete reversal of each with Ad-FoxO3 co-infection in quiescent and growth conditions; Ad-FoxO3 OE leading to enhanced cytosolic expression of phosphorylated and total FoxO3, both reduced with Ad-Smad3 co-infection in quiescent and growth conditions; Ad-FoxO3 inducing expression and activity of the ubiquitin ligase MuRF-1, which was reversed with concomitant Ad-Smad3 OE; and combined Smad3/FoxO3 OE reversing both the pro-growth impact of singular Smad3 and the cytostatic impact of singular FoxO3. A primary takeaway from these observations is the capacity of FoxO3 to reverse growth-promoting effects of Smad3 in ASM cells. Additional findings lend support for reciprocal antagonism of Smad3 on FoxO3-induced cytostasis, and these effects are dependent upon discrete phosphorylation states and cellular localization and involve MuRF-1 in the control of ASM cell growth. Lastly, results showing capacity of FoxO3 to normalize Smad3-induced ASM cell growth largely support our hypothesis, and overall findings provide evidence for utility of Smad3 and/or FoxO3 as potential therapeutic targets against abnormal ASM growth in the context of CVD.