Search

Objective: Large language models such as ChatGPT have demonstrated significant potential in question-answering within ophthalmology, but there is a paucity of literature evaluating its ability to generate clinical assessments and discussions. The objectives of this study were to (1) assess the accuracy of assessment and plans generated by ChatGPT and (2) evaluate ophthalmologists' abilities to distinguish between responses generated by clinicians versus ChatGPT., Design: Cross-sectional mixed-methods study., Subjects: Sixteen ophthalmologists from a single academic center, of which 10 were board-eligible and 6 were board-certified, were recruited to participate in this study., Methods: Prompt engineering was used to ensure ChatGPT output discussions in the style of the ophthalmologist author of the Medical College of Wisconsin Ophthalmic Case Studies. Cases where ChatGPT accurately identified the primary diagnoses were included and then paired. Masked human-generated and ChatGPT-generated discussions were sent to participating ophthalmologists to identify the author of the discussions. Response confidence was assessed using a 5-point Likert scale score, and subjective feedback was manually reviewed., Main Outcome Measures: Accuracy of ophthalmologist identification of discussion author, as well as subjective perceptions of human-generated versus ChatGPT-generated discussions., Results: Overall, ChatGPT correctly identified the primary diagnosis in 15 of 17 (88.2%) cases. Two cases were excluded from the paired comparison due to hallucinations or fabrications of nonuser-provided data. Ophthalmologists correctly identified the author in 77.9% ± 26.6% of the 13 included cases, with a mean Likert scale confidence rating of 3.6 ± 1.0. No significant differences in performance or confidence were found between board-certified and board-eligible ophthalmologists. Subjectively, ophthalmologists found that discussions written by ChatGPT tended to have more generic responses, irrelevant information, hallucinated more frequently, and had distinct syntactic patterns (all P < 0.01)., Conclusions: Large language models have the potential to synthesize clinical data and generate ophthalmic discussions. While these findings have exciting implications for artificial intelligence-assisted health care delivery, more rigorous real-world evaluation of these models is necessary before clinical deployment., Financial Disclosures: The author(s) have no proprietary or commercial interest in any materials discussed in this article., (© 2024 by the American Academy of Ophthalmology.)

Purpose: To evaluate the effects of mechanical disruption of the inner limiting membrane (ILM) on the ability to target interventions to the inner neurosensory retina in a rodent model. Our study used an animal model to gain insight into the normal physiology of the ILM and advances our understanding of the effects of mechanical ILM removal on the viral transduction of retinal ganglion cells and retinal ganglion cell transplantation., Methods: The ILM in the in vivo rat eye was disrupted using mechanical forces applied to the vitreoretinal interface. Immunohistology and electron microscopy were used to verify the removal of the ILM in retina flatmounts and sections. To assess the degree to which ILM disruption enhanced transvitreal access to the retina, in vivo studies involving intravitreal injections of adeno-associated virus (AAV) to transduce retinal ganglion cells (RGCs) and ex vivo studies involving co-culture of human stem cell-derived RGCs (hRGCs) on retinal explants were performed. RGC transduction efficiency and transplanted hRGC integration with retinal explants were evaluated by immunohistology of the retinas., Results: Mechanical disruption of the ILM in the rodent eye was sufficient to remove the ILM from targeted retinal areas while preserving the underlying retinal nerve fiber layer and RGCs. Removal of the ILM enhanced the transduction efficiency of intravitreally delivered AAV threefold (1380.0 ± 290.1 vs. 442.0 ± 249.3 cells/mm2; N = 6; P = 0.034). Removal of the ILM was also sufficient to promote integration of transplanted RGCs within the inner retina., Conclusions: The ILM is a barrier to transvitreally delivered agents including viral vectors and cells. Mechanical removal of the ILM is sufficient to enhance access to the inner retina, improve viral transduction efficiencies of RGCs, and enhance cellular integration of transplanted RGCs with the retina.

Prcis: We updated a clinical decision support tool integrating predicted visual field (VF) metrics from an artificial intelligence model and assessed clinician perceptions of the predicted VF metric in this usability study., Purpose: To evaluate clinician perceptions of a prototyped clinical decision support (CDS) tool that integrates visual field (VF) metric predictions from artificial intelligence (AI) models., Methods: Ten ophthalmologists and optometrists from the University of California San Diego participated in 6 cases from 6 patients, consisting of 11 eyes, uploaded to a CDS tool ("GLANCE", designed to help clinicians "at a glance"). For each case, clinicians answered questions about management recommendations and attitudes towards GLANCE, particularly regarding the utility and trustworthiness of the AI-predicted VF metrics and willingness to decrease VF testing frequency., Main Outcomes and Measures: Mean counts of management recommendations and mean Likert scale scores were calculated to assess overall management trends and attitudes towards the CDS tool for each case. In addition, system usability scale scores were calculated., Results: The mean Likert scores for trust in and utility of the predicted VF metric and clinician willingness to decrease VF testing frequency were 3.27, 3.42, and 2.64, respectively (1=strongly disagree, 5=strongly agree). When stratified by glaucoma severity, all mean Likert scores decreased as severity increased. The system usability scale score across all responders was 66.1±16.0 (43rd percentile)., Conclusions: A CDS tool can be designed to present AI model outputs in a useful, trustworthy manner that clinicians are generally willing to integrate into their clinical decision-making. Future work is needed to understand how to best develop explainable and trustworthy CDS tools integrating AI before clinical deployment., Competing Interests: Disclosure: L.M.Z. is a consultant for Abbvie Inc. Digital Diagnostics, receives research funding from the National Eye Institute, Carl Zeiss Meditec Inc., Heidelberg Engineering GmbH, Optovue Inc, Topcon Medical Systems Inc, and has patented intellectual property with Zeiss Meditec. R.N.W. is a consultant for Abbvie, Aerie Pharmaceuticals, Allergan, Equinox, Iantrek, Implandata, Nicox, Topcon Medical, and receives research funding from the National Eye Institute, National Institute on Minority Health and Health Disparities, Bausch & Lomb, Topcon Medical, Heidelberg Engineering, Carl Zeiss Meditec, Optovue, Centervue, and has patented intellectual property licensed by the University of California San Diego to Zeiss Meditec and Toromedes. The remaining authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To determine the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in postmortem ocular specimens of patients with severe COVID-19 disease., Patients and Methods: Postmortem conjunctival (28 samples), aqueous humor (30 samples) and vitreous humor (30 samples) specimens were obtained bilaterally from the eyes of 15 deceased COVID-19 patients within one hour of death. The presence of viral RNA was evaluated in samples using Real-time reverse transcriptase-polymerase chain reaction (RT-PCR)., Results: Positive RT-PCR SARS-COV-2 results were found in one conjunctival and 2 vitreous humor samples. All aqueous humor samples tested negative for the presence of SARS-COV-2 RNA. Of note, three positive samples were obtained from three different patients. The overall prevalence of positive RT-PCR ocular samples was 3.4% among all samples and 20% at the patient level., Conclusion: SARS-CoV-2 RNA is detectable in postmortem conjunctival and vitreous humor samples of patients with severe COVID-19.

Ruthenium-alkylidene initiated ring-opening metathesis polymerization has been realized under solid-state conditions by employing a mechanochemical ball milling method. This method promotes greenness and broadens the scope to include mechano-exclusive products. The carbene- and pyridine-based Grubbs 3 rd -generation complex outperformed other catalysts and maintained similar mechanistic features of solution-phase reactions. High-speed ball milling provides sufficient mixing and energy to the solid reaction mixture, which is composed of an initiator and monomers, to minimize or eliminate the use of solvents. Therefore, the solubility and miscibility of monomers and Ru-initiators are not limiting factors in solid-state ball milling. A wide variety of solid monomers, including ionomers, fluorous monomers, and macromonomers, were successfully polymerized under ball milling conditions. Importantly, direct copolymerization of immiscible (ionic/hydrophobic) monomers exemplifies the synthesis of mechano-exclusive polymers that are difficult to make using traditional solution procedures. Finally, the addition of a small amount of a liquid additive ( i.e. , liquid-assisted grinding) minimized chain-degradation, enabling high-molecular-weight polymer synthesis., Competing Interests: The authors declare no competing financial interest., (This journal is © The Royal Society of Chemistry.)

Purpose: To compare the differences in retinal vessel density (VD) between topical administration of latanoprostene bunod (LBN) ophthalmic solution 0.024% and timolol maleate 0.5% in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT) and normal subjects., Design: Randomized, single center, crossover clinical trial., Methods: Eligible subjects were examined during 6 study visits over 12 weeks. All subjects were randomized in a 1:1 ratio to LBN dosed once daily or timolol dosed twice daily in both eyes (OU) for a duration of 4 weeks each, separated by a 2-week washout period. A comprehensive eye examination OU was performed at each visit. Testing was performed with optical coherence tomography and optical coherence tomography angiography (optic nerve and macula), as well as visual field examination, on the study eye at baseline and before and after each treatment., Results: One eye from each of 50 patients was enrolled (10 healthy patients, 26 patients with OHT, and 14 patients with OAG). After administration of LBN there was significantly increased macular VD (0.76% [0.20%-1.33%], P = 0.009) and a trend in increasing peripapillary VD in patients with OAG and patients with OHT. In contrast, after administration of timolol, there were no differences in macular VD, and a decrease in peripapillary VD only was observed in the nasal inferior sector (-0.56% [-1.08% to -0.03%], P = .04) in patients with OAG and patients with OHT. No change in peripapillary or macular VD was observed in the normal subjects (P > .05 for all)., Conclusions: Topical administration of LBN enhanced macular VD in patients with OAG or patients with OHT. In contrast, timolol administration did not have any effect on VD., (Copyright © 2022 Elsevier Inc. All rights reserved.)

We demonstrate catalytic organic synthesis by Resonant Acoustic Mixing (RAM): a mechanochemical methodology that does not require bulk solvent or milling media. Using as model reactions ruthenium-catalyzed ring-closing metathesis and copper-catalyzed sulfonamide-isocyanate coupling, RAM mechanosynthesis is shown to be faster, operationally simpler than conventional ball-milling, while also providing the first example of a mechanochemical strategy for ruthenium-catalyzed ene-yne metathesis. Reactions by RAM are readily and directly scaled-up without any significant changes in reaction conditions, as shown by the straightforward 200-fold scaling-up of the synthesis of the antidiabetic drug Tolbutamide, from hundreds of milligrams directly to 30 grams., (© 2022 Wiley-VCH GmbH.)

Purpose: To investigate the characteristics and rate of central visual field loss after optic disc hemorrhage (DH)., Design: Prospective cohort study., Methods: Three hundred forty-three eyes of 220 subjects who had ≥3 years of follow-up with a minimum of 5 visits with 10-2 and 24-2 visual field (VF) were recruited. Rates of 10-2 mean deviation (MD) loss in each hemifield and predefined zones were compared using linear mixed-effects models in DH and non-DH eyes. Clustered pointwise regression analysis was also used to define central VF progressors and compared with 24-2 VF loss using guided progression analysis., Results: Thirty-nine eyes with DH and 304 eyes without DH had a mean follow-up of 5.2 years. Eyes with DH had rates of 10-2 MD loss that were 3 times faster than non-DH eyes (mean difference -0.36 dB/year [95% confidence interval 0.54-0.18]; P < .001) and were 3.7 times more likely to progress (P = .002). A larger proportion of glaucomatous eyes showed central VF progression rather than peripheral VF progression in the DH group (30.8% vs. 20.5%) compared with the non-DH group (10.9% vs. 9.2%). In early glaucoma, the rate of 10-2 MD loss was 5.5 times faster in DH eyes than in non-DH eyes (P < .001). Superonasal and superotemporal central VF regions progressed more rapidly than other regions, especially in DH eyes., Conclusion: Central VF loss is accelerated in glaucoma eyes with DH and it corresponds topographically to the DH location. In patients with glaucoma with DH, one should consider supplementing 10-2 VFs with 24-2 VFS to monitor the disease., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Colloidal bismuth therapeutics have been used for hundreds of years, yet remain mysterious. Here we report an X-ray pair distribution function (PDF) study of the solvolysis of bismuth disalicylate, a model for the metallodrug bismuth subsalicylate (Pepto-Bismol). This reveals catalysis by traces of water, followed by multistep cluster growth. The ratio of the two major species, {Bi 9 O 7 } and {Bi 38 O 44 }, depends on exposure to air, time, and the solvent. The solution-phase cluster structures are of significantly higher symmetry in comparison to solid-state analogues, with reduced off-center Bi 3+ displacements. This explains why such "magic-size" clusters can be both stable enough to crystallize and sufficiently labile for further growth.

Mechanochemistry enables rapid access to boron imidazolate frameworks (BIFs), including ultralight materials based on Li and Cu(i) nodes, as well as new, previously unexplored systems based on Ag(i) nodes. Compared to solution methods, mechanochemistry is faster, provides materials with improved porosity, and replaces harsh reactants ( e.g. n -butylithium) with simpler and safer oxides, carbonates or hydroxides. Periodic density-functional theory (DFT) calculations on polymorphic pairs of BIFs based on Li + , Cu + and Ag + nodes reveals that heavy-atom nodes increase the stability of the open SOD-framework relative to the non-porous dia-polymorph., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Purpose: To compare spectral-domain optical coherence tomography (SDOCT) measured circumpapillary retinal nerve fiber layer (cpRNFL) among 4 glaucomatous optic disc phenotypes in early glaucoma., Design: Clinical cohort study METHODS: In this study, 218 early glaucoma eyes that had at least 3 years of follow-up and a minimum of 4 SDOCT scans were recruited. The optic discs were classified into 4 types based on appearance: 76 generalized cup enlargement (GE), 53 focal ischemic (FI), 22 myopic glaucomatous (MY), and 67 senile sclerotic (SS). A linear mixed effects model was used to compare the rates of global and regional cpRNFL thinning among optic disc phenotypes., Results: After adjusting for confounders, the SS group (mean [95% CI]: -1.01 [-1.30, -0.73] µm/y) had the fastest mean rate of global cpRNFL thinning followed by FI (-0.77 [-0.97, -0.57] µm/y), MY (0.59 [-0.81, -0.36] µm/y), and GE (-0.58 [-0.75, -0.40] µm/y) at P < .001. The inferior temporal sector had the fastest rate of cpRNFL thinning among the regional measurements except for the MY group (-0.68 [-1.10, -0.26] µm/y, P = .002). In the multivariable analysis, GE (P = .002) and MY (P = .010) phenotypes were associated with significantly slower global rates of cpRNFL thinning compared with the SS phenotype., Conclusions: Rates of cpRNFL thinning were different among the 4 glaucomatous optic disc phenotypes. Those patients with early glaucoma with SS phenotype have the fastest cpRNFL thinning. These patients may benefit from more frequent monitoring and the need to advance therapy if cpRNFL thinning is detected., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: To evaluate the integrative potential of neural stem cells (NSCs) with the visual system and characterize effects on the survival and axonal regeneration of axotomized retinal ganglion cells (RGCs)., Methods: For in vitro studies, primary, postnatal rat RGCs were directly cocultured with human NSCs or cultured in NSC-conditioned media before their survival and neurite outgrowth were assessed. For in vivo studies, human NSCs were transplanted into the transected rat optic nerve, and immunohistology of the retina and optic nerve was performed to evaluate RGC survival, RGC axon regeneration, and NSC integration with the injured visual system., Results: Increased neurite outgrowth was observed in RGCs directly cocultured with NSCs. NSC-conditioned media demonstrated a dose-dependent effect on RGC survival and neurite outgrowth in culture. NSCs grafted into the lesioned optic nerve modestly improved RGC survival following an optic nerve transection (593 ± 164 RGCs/mm2 vs. 199 ± 58 RGCs/mm2; P < 0.01). Additionally, RGC axonal regeneration following an optic nerve transection was modestly enhanced by NSCs transplanted at the lesion site (61.6 ± 8.5 axons vs. 40.3 ± 9.1 axons, P < 0.05). Transplanted NSCs also differentiated into neurons, received synaptic inputs from regenerating RGC axons, and extended axons along the transected optic nerve to incorporate with the visual system., Conclusions: Human NSCs promote the modest survival and axonal regeneration of axotomized RGCs that is partially mediated by diffusible NSC-derived factors. Additionally, NSCs integrate with the injured optic nerve and have the potential to form neuronal relays to restore retinofugal connections.

We present a new class of anionic metallohelicates based on an abundant, industrially relevant salicylic acid derivative, leading to discrete double and triple-stranded architectures based on divalent and trivalent metals (Cu 2+ , Fe 3+ , respectively). The ability to assemble the metallohelicates in a solvent-free environment presents the opportunity to develop an inexpensive and environmentally-friendly design of helicate materials.

Purpose: To investigate central visual field (VF) defects among 4 phenotypes of glaucomatous optic discs., Design: Cross-sectional study., Methods: Optic disc phenotypes were determined in eyes with definite or suspected glaucoma that had a 24-2 VF with mean deviation (MD) better than -12 dB and a 10-2 VF. 10-2 VFs were classified as abnormal based on a cluster criterion. Additionally, the average of the total deviation values at each 10-2 test point was compared by optic disc phenotype., Results: The following 4 glaucomatous optic disc phenotypes were identified in 448 eyes of 309 patients: focal ischemic (FI) (n = 121); generalized cup enlargement (GE) (n = 109); myopic glaucoma (MY) (n = 66); and senile sclerotic (SS) (n = 152). Although 24-2 VF MD values were similar among optic disc phenotypes, GE eyes had higher 10-2 VF MD (P = .004), as well as lower 24-2 VF pattern standard deviations (PSD) (P < .001) and VF 10-2 PSD (P < .001) than the other phenotypes. The prevalence of an abnormal VF 10-2 was highest in FI eyes (78.5%) and lowest in GE eyes (50.5%) (P < .001). In glaucoma suspects, the prevalence of an abnormal 10-2 VF was highest in the MY eyes (31.2%) and FI eyes (23.5%) and lowest in GE eyes (8.6%). In mild glaucoma, the prevalence of abnormal 10-2 VF test results was highest in FI eyes (79.2%) and lowest in GE eyes (44.4%) (P = .013)., Conclusions: The severity and prevalence of central VF loss varied among different glaucomatous optic disc phenotypes. Glaucomatous eyes with FI and MY optic disc phenotypes are more likely to have 10-2 VF loss, particularly in early disease, and especially may benefit from testing with both 10-2 and 24-2 VF tests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: To compare the efficacy of intraoperative scleral application with subconjunctival injection of mitomycin C (MMC) in trabeculectomy., Design: Prospective, randomized, interventional study., Methods: This study took place in a single clinical practice in an academic setting. Patients had medically uncontrolled glaucoma as indicated by high intraocular pressure (IOP), worsening visual field, or optic nerve head changes in whom primary trabeculectomy was indicated. Patients were older than 18 years with medically uncontrolled glaucoma and no history of incisional glaucoma surgery. Patients were randomized to MMC delivered by preoperative subconjunctival injection or by intraoperative direct scleral application using surgical sponges during trabeculectomy. Comprehensive eye examinations were conducted at 1 day, 1 week, 6 weeks, 3 months, and 6 months postoperatively. Subconjunctival 5-fluorouracil injections were given postoperatively, as needed. The primary outcome was the proportion of patients who demonstrated IOP of <21 mm Hg and ≥30% reduction in IOP from baseline. Secondary outcome measures included the number of IOP-lowering medications, bleb morphology using the Indiana Bleb Appearance Grading Scale, and complication rates., Results: Participants (n = 100) were randomized into groups matched for baseline demographics, glaucoma status, and baseline IOP. At 6 months, there were no significant differences between the injection (n = 38) and sponge (n = 40) groups in surgical success (P = .357), mean IOP (P = .707), number of glaucoma medications (P = 1.000), bleb height (P = .625), bleb extension (P = .216), bleb vascularity (P = .672), or complications rates., Conclusion: Both techniques of MMC delivery (subconjunctival injection and direct scleral application) resulted in comparable surgical outcomes and bleb morphologies., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Retinal ganglion cell (RGC) axons converge at the optic nerve head to convey visual information from the retina to the brain. Pathologies such as glaucoma, trauma, and ischemic optic neuropathies injure RGC axons, disrupt transmission of visual stimuli, and cause vision loss. Animal models simulating RGC axon injury include optic nerve crush and transection paradigms. Each of these models has inherent advantages and disadvantages. An optic nerve crush is generally less severe than a transection and can be used to assay axon regeneration across the lesion site. However, differences in crush force and duration can affect tissue responses, resulting in variable reproducibility and lesion completeness. With optic nerve transection, there is a severe and reproducible injury that completely lesions all axons. However, transecting the optic nerve dramatically alters the blood brain barrier by violating the optic nerve sheath, exposing the optic nerve to the peripheral environment. Moreover, regeneration beyond a transection site cannot be assessed without reapposing the cut nerve ends. Furthermore, distinct degenerative changes and cellular pathways are activated by either a crush or transection injury. The method described here incorporates the advantages of both optic nerve crush and transection models while mitigating the disadvantages. Hydrostatic pressure delivered into the optic nerve by microinjection completely transects the optic nerve while maintaining the integrity of the optic nerve sheath. The transected optic nerve ends are reapposed to allow for axon regeneration assays. A potential limitation of this method is the inability to visualize the complete transection, a potential source of variability. However, visual confirmation that the visible portion of the optic nerve has been transected is indicative of a complete optic nerve transection with 90-95% success. This method could be applied to assess axon regeneration promoting strategies in a transection model or investigate interventions that target the axonal compartments.

A mechanochemical route is developed for room-temperature and solvent-free derivatization of different types of amides into carbamoyl isatins (up to 96 % conversion or yield), benzamides (up to 81 % yield), and imides (up to 92 % yield). In solution, this copper-catalyzed coupling either does not take place or requires high temperatures at which it may also be competing with alternative thermal reactivity, highlighting the beneficial role of mechanochemistry for this reaction. Such behavior resembles the previously investigated coupling with sulfonamide substrates, suggesting that this type of C-N coupling is an example of a mechanochemically favored reaction, for which mechanochemistry appears to be a favored environment over solution., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

We present a rapid and readily scalable methodology for the mechanosynthesis of diverse metal-organic frameworks (MOFs) in the absence of milling media typically required for other types of mechanochemical syntheses. We demonstrate the use of liquid-assisted resonant acoustic mixing (LA-RAM) methodology for the synthesis of three- and two-dimensional MOFs based on Zn(ii), Co(ii) and Cu(ii), including a mixed ligand system. Importantly, the LA-RAM approach also allowed the synthesis of the ZIF-L framework that has never been previously obtained in a mechanochemical environment, as well as its Co(ii) analogue. Straightforward scale-up from milligrams to at least 25 grams is demonstrated using the metastable framework ZIF-L as the model., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Purpose: To evaluate aqueous humor outflow (AHO) in intact eyes of live human subjects during cataract surgery using fluorescein aqueous angiography., Methods: Aqueous angiography was performed in 8 live human subjects (56 to 86 y old; 2 men and 6 women). After anesthesia, fluorescein (2%) was introduced into the eye [either alone or after indocyanine green (ICG; 0.4%)] from a sterile, gravity-driven constant-pressure reservoir. Aqueous angiographic images were obtained with a Spectralis HRA+OCT and FLEX module (Heidelberg Engineering). Using the same device, anterior-segment optical coherence tomography (OCT) and infrared images were also concurrently taken with aqueous angiography., Results: Fluorescein aqueous angiography in the live human eye showed segmental AHO patterns. Initial angiographic signal was seen on average by 14.0±3.0 seconds (mean±SE). Using multimodal imaging, angiographically positive signal colocalized with episcleral veins (infrared imaging) and intrascleral lumens (anterior-segment OCT). Sequential aqueous angiography with ICG followed by fluorescein showed similar segmental angiographic patterns., Discussion: Fluorescein aqueous angiography in live humans was similar to that reported in nonhuman primates and to ICG aqueous angiography in live humans. As segmental patterns with sequential angiography using ICG followed by fluorescein were similar, these tracers can now be used sequentially, before and after trabecular outflow interventions, to assess their effects on AHO in live human subjects.

Noble metals are valued, critical elements whose chemical activation or recycling is challenging, and traditionally requires high temperatures, strong acids or bases, or aggressive complexation agents. By using elementary palladium and gold, demonstrated here is the use of mechanochemistry for noble-metal activation and recycling by mild, clean, solvent-free, and room-temperature chemistry. The process leads to direct, efficient, one-pot conversion of the metals, including spent catalysts, into either simple water-soluble salts or metal-organic catalysts., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Mechanochemistry enables enzymatic cleavage of cellulose into glucose without bulk solvents, acids, other aggressive reagents, or substrate pre-treatment. This clean mechanoenzymatic process (coined RAging) is also directly applicable to biomass, avoids many limitations associated with the use of cellulases, and produces glucose concentrations greater than three times that obtained by conventional methods., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

We present a rapid and efficient method to generate a family of platinum supramolecular square complexes, including previously inaccessible targets, through the use of ball milling mechanochemistry. This one-pot, two-step process occurs in minutes and enables the synthesis of the squares [Pt 4 (en) 4 (N∩N) 4 ][CF 3 SO 3 ] 8 (en= ethylenediamine, N∩N = 4,4'-bipyridine derivatives) from commercially available precursor K 2 PtCl 4 in good to excellent yields. In contrast, solution-based assembly requires heating the reagents for weeks and gives lower yields. Mechanistic investigations into this remarkable rate acceleration revealed that solution-based assembly (refluxing for days) results in the formation of large oligomeric side-products that are difficult to break down into the desired squares. On the other hand, ball milling in the solid state is rapid and appears to involve smaller intermediates. We examined the binding of the new supramolecular squares to guanine quadruplexes, including oncogene and telomere-associated DNA and RNA sequences. Sub-micromolar binding affinities were obtained by fluorescence displacement assays (FID) and isothermal titration calorimetry (ITC), with binding preference to telomere RNA (TERRA) sequences. ITC showed a 1:1 binding stoichiometry of the metallosquare to TERRA, while the stoichiometry was more complex for telomeric quadruplex DNA and a double-stranded DNA control.

The past decade has seen a reawakening of solid-state approaches to chemical synthesis, driven by the search for new, cleaner synthetic methodologies. Mechanochemistry, i.e., chemical transformations initiated or sustained by mechanical force, has been advancing particularly rapidly, from a laboratory curiosity to a widely applicable technique that not only enables a cleaner route to chemical transformations but offers completely new opportunities in making and screening for molecules and materials. This Outlook provides a brief overview of the recent achievements and opportunities created by mechanochemistry, including access to materials, molecular targets, and synthetic strategies that are hard or even impossible to access by conventional means., Competing Interests: The authors declare no competing financial interest.

Cervical cancer, the second most common cancer affecting women in Northern Brazil, is strongly associated with human papillomavirus (HPV) infection. Diseases affecting the immune state of a patient, including autoimmune diseases like systemic lupus erythematosus (SLE), can lead to persistent HPV infection and cancer. We evaluated cervical HPV prevalence and the associated risk factors in 70 women with SLE in the city of Belém, located in Brazilian Amazon. HPV DNA was detected by PCR using primers MY9 and MY11. HPV subtypes were determined by real-time PCR, using specific probes. Overall, prevalence of cervical HPV in women with SLE was 22.8%. HPV prevalence was significantly higher in younger women (aged 18-25 years; 75%, p< 0.0001), in women who had not given birth (50%, p = 0.01), and in women with no prior pregnancy (57%, p = 0.003). Five women (7.1%) had Pap smears with a cytopathological outcome suggestive of HPV; four of these women were HPV-positive. No women with both, SLE and HPV, had a normal Pap smear. Of the women diagnosed with SLE in the last 1-5 years, 75% was HPV-positive (p = 0.04). The two most prevalent HPV subtypes were HPV 58 (37.5%) and HPV 31 (31.3%). These results are important for understanding HPV infection in women with SLE and are valuable tools for developing cervical cancer prevention strategies and health management policies.

The objective of this study is to describe the time trend of coefficients of incidence and mortality associated with AIDS in children and adolescents. An ecological time trend study was conducted among individuals under 14 living in the regional context of high incidence of AIDS - Porto Alegre and the State of Rio Grande do Sul - from 1996 to 2012. For this purpose, a segmented regression model was adjusted for age categories and place of residence. AIDS morbidity and mortality indicators in Porto Alegre are still higher than those registered in the State, the southern region and other areas of the country. In Porto Alegre, 59.1% of cases (371/628) occurred in children under four years of age, the incidence showed peaks in the period and the mortality dropped from 9 to 2 per 100,000. A significant decreasing in annual percentage change in mortality was observed especially in children under 1 year of age in Porto Alegre. This drop may be related to prevention and treatment of pregnant women. The challenge is to identify possible fragilities of the STD/AIDS Program and its vulnerable points in order to make specific interventions and investments with a greater impact potential.

Heavy metals, such as methylmercury, are key environmental pollutants that easily reach human beings by bioaccumulation through the food chain. Several reports have demonstrated that endocrine organs, and especially the pituitary gland, are potential targets for mercury accumulation; however, the effects on the regulation of hormonal release are unclear. It has been suggested that serum prolactin could represent a biomarker of heavy metal exposure. The aim of this study was to evaluate the effect of methylmercury on prolactin release and the role of the nitrergic system using prolactin secretory cells (the mammosomatotroph cell line, GH3B6). Exposure to methylmercury (0-100 μM) was cytotoxic in a time- and concentration-dependent manner, with an LC50 higher than described for cells of neuronal origin, suggesting GH3B6 cells have a relative resistance. Methylmercury (at exposures as low as 1 μM for 2 h) also decreased prolactin release. Interestingly, inhibition of nitric oxide synthase by N-nitro-L-arginine completely prevented the decrease in prolactin release without acute neurotoxic effects of methylmercury. These data indicate that the decrease in prolactin production occurs via activation of the nitrergic system and is an early effect of methylmercury in cells of pituitary origin.

We describe the development of a mechanochemical approach for Ru-catalyzed olefin metathesis, including cross-metathesis and ring-closing metathesis. The method uses commercially available catalysts to achieve high-yielding, rapid, room-temperature metathesis of solid or liquid olefins on a multigram scale using either no or only a catalytic amount of a liquid.

Introduction: Postural deviations have been linked to a series of different kinds of pain and dysfunction. However, posture is not an easy subject to study, mainly because postural assessments are still scientifically inaccurate, such as photography, or expensive, such as MRI, whereas others, such as X-ray, involve radiation problems. The aim of this literature review was to search for new scientific methods for assessing posture and to discuss which among both new and old methods are best for scientific and clinical objectives., Materials and Methods: The Medline and Lilacs databases were searched for the period 2003 to 2013 with the use of the following keywords: "posture" and "postural.", Results: A total of 452 articles that assessed posture in some way were found. Twenty-two articles were selected, and 11 relevant types of technologies were described., Discussion: The relevant technologies discussed were force plate; pictures; goniometers, inclinometers, tape, and other devices; 3D analysis; 3D X-ray; sensors; electromyography; Kinect; magnetic resonance imaging; 4D computed tomography; and infrared., Conclusion: There is enough technology to make a very good quantitative evaluation possible. For example, the 3D MRI or the 4D CT can register static and dynamic posture. Other cheaper solutions may use combined and synchronized equipments. However, these synchronizations still require validation., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Adult CNS neurons exhibit a reduced capacity for growth compared to developing neurons, due in part to downregulation of growth-associated genes as development is completed. We tested the hypothesis that SnoN, an embryonically regulated transcription factor that specifies growth of the axonal compartment, can enhance growth in injured adult neurons. In vitro, SnoN overexpression in dissociated adult DRG neuronal cultures significantly enhanced neurite outgrowth. Moreover, TGF-β1, a negative regulator of SnoN, inhibited neurite outgrowth, and SnoN over-expression overcame this inhibition. We then examined whether SnoN influenced axonal regeneration in vivo: indeed, expression of a mutant form of SnoN resistant to degradation significantly enhanced axonal regeneration following cervical spinal cord injury, despite peri-lesional upregulation of TGF-β1. Thus, a developmental mechanism that specifies extension of the axonal compartment also promotes axonal regeneration after adult CNS injury.

The present study investigated the existence of a relationship between subjective sadness and body posture in 28 women, aged between 20 and 39 years, who had a normal body mass indices (or were underweight) and an absence of neurological, psychiatric or musculoskeletal disorders. The postural parameter photographed was protraction of the shoulder. The degree of sadness was rated by analog scales representing current and usual sadness. The results indicated that a relationship exists between protraction of the shoulder and usual sadness (p = 0.05). However, there was no relationship between current sadness and the shoulder position. In conclusion, the usual sadness can lead to shoulder protraction., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Objective: Homocysteine and sepsis are both associated with inflammation and endothelial activation. Therefore this study was aimed to evaluate if the plasma homocystein level is related with the septic patient clinical severity., Methods: Severe sepsis or septic shock patients, with less than 48 hours from organ dysfunction start, were admitted to this prospective observational study. Homocysteine levels were determined by the time of study admission and then on the Days 3, 7 and 14. The homocysteine association with the Sequential Organ Failure Assessment (SOFA) score was evaluated using the Sperman test, and its association with mortality using the Mann-Whitney test. A p<0.05 value was considered statistically significant., Results: Twenty one patients were enrolled, and 60 blood samples were collected to measure total homocysteine [median 6.92 (5.27 - 9.74 μmol/L)]. The Sperman correlation test showed no association between homocysteine and SOFA ( r=0.15 and p=0.26). Also no correlation was found for the homocysteine level by the study admission time and the difference between the Day 3 SOFA score versus by study admission (deltaSOFA) (r=0.04 and p=0.87). Homocysteine variation between the Day 3 and the study admission (deltaHmc) and SOFA score variation in the same period were not correlated (r=-0.11 and p=0.66). Homocysteine by the study admission was not correlated with death in intensive care unit rate (p= 0.46) or in-hospital death rate (p = 0.13). This was also true for deltaHmc (p=0.12 and p=0.99, respectively)., Conclusion: Baseline homocysteine levels and its variations within the first dysfunction days were not related with septic patients' worsened organ function parameters or mortality.

Background and Objectives: The interscalene is one of the most common approaches used in brachial plexus block. However, the association of this approach with the ipsilateral blockade of the phrenic nerve has been demonstrated. The resulting diaphragmatic dysfunction causes changes in lung mechanics, which can be potentially deleterious in patients with limited respiratory reserve. The objective of the present study was to evaluate the repercussion of interscalene brachial plexus block on pulmonary function by measuring forced vital capacity (FVC)., Methods: This is a double-blind study with 30 patients, physical status ASA I or II, randomly separated into two groups of 15 patients each; 0.5% ropivacaine (Ropi Group) or 0.5% bupivacaine with epinephrine (Bupi Group) was administered. A peripheral nerve stimulator was used, and 30 mL of the local anesthetic were administered. Four spirometries were done in each patient: before the blockade, 30 minutes, four hours, and six hours after the blockade. Patients were not sedated., Results: One patient in the Ropi Group and three patients in the Bupi Group were excluded from the study due to failure of the blockade. The Ropi Group showed maximal FVC reduction at 30 minutes (25.1%), with a tendency for recovery from this point on. With bupivacaine, the reduction in FVC was less important at the different study moments; an additional reduction was observed between 30 (15.8%) and four hours (17.3%), but it was not statistically significant. A tendency for recovery was observed from four hours on. In both groups, the FVC six hours after the blockade was still below baseline levels., Conclusions: Interscalene block reduces FVC in most cases. Changes were more pronounced in the Ropivacaine group.

Cryptococcus neoformans and Cryptococcus gattii are important agents of meningoencephalitis in humans in the city of Belém. This clinical data suggests that the region may be a highly endemic area for the pathogenic Cryptococcus species within the state of Pará (PA), Northern Brazil. Preliminary analysis of 11 environmental samples from the city of Belém showed two positive locations, including a hollow of a kassod tree (Senna siamea) colonized simultaneously by C. gattii molecular type VGII and C. neoformans molecular type VNI, and a birdcage in a commercial aviary positive for C. neoformans, molecular type VNI. This is the first evidence of an environmental occurrence of molecular types VNI and VGII in PA.

Objective: To assess cognitive and behavioral development at preschool age of children born preterm and with low birth weight and raised in a developing country., Methods: Prospective cross-sectional study of 80 neonates born in a university hospital in southern Brazil. Neuropsychological assessment at age 4-5 years included the Wechsler Preschool and Primary Scale of Intelligence (WPPSI), Conners' Parent Rating Scale-Revised, Denver test and neurological examination. Perinatal and early neuropsychomotor development information was collected from the database during follow-up. Results were related to birth weight, sex and gestational age., Results: WPPSI scores were: total intelligence quotient (IQ) 88.00+/-16.96, verbal IQ 89.72+/-16.72, and executive IQ 88.12+/-15.71 for the group with less than 1,500 grams; and total IQ 91.11+/-14.73, verbal IQ 93.36+/-12.65, and executive IQ 90.20+/-16.06 for the group between 1,500 and 2,500 grams. The best scores were obtained in tests that evaluated capacity of abstraction and symbolization, picture completion and common perception, in which only 5% and 6.3% of the children had abnormal results, respectively. The lowest scores were obtained in tests that evaluated visual-motor coordination and flexibility-speed of reasoning, in which 27.5% and 16.3% of the children had abnormal results, respectively. A total of 32.5% had abnormal results in the arithmetic tests. Behaviors related to attention deficit/hyperactivity disorder (ADHD) were observed in 48% of the sample. Low score in the Bayley Mental Scale and abnormal result in the Denver test were significantly correlated to ADHD (p = 0.017 and p = 0.004). Abnormal results in the Bayley Mental Scale (p < 0.001), Denver test (p < 0.001) and neurological examination (p = 0.002) were associated with lower IQ., Conclusions: The results revealed an increased incidence of behavioral and cognitive disorders at preschool age.

Introduction: Central venous oxygen saturation (SvcO2) has been proposed as an alternative for mixed venous oxygen saturation (SvO2), with a variable level of acceptance according to available data. This study aimed to evaluate possible differences between SvO2 and SvcO2 or atrial venous saturation (SvaO2), with emphasis on the role of cardiac output and their impact on clinical management of the septic patient., Methods: This is an observational, prospective study of patients with septic shock monitored by pulmonary artery catheter. Blood was obtained simultaneously for SvcO2, SvO2 and SvaO2 determination. Linear correlation (significant if p<0.05) and agreement analysis (Bland-Altman) were performed with samples and subgroups according to cardiac output. Moreover, agreement about clinical management based on these samples was evaluated., Results: Sixty one measurements from 23 patients were obtained, median age of 65.0 (49.0-75.0) years and mean APACHE II of 27.7±6.3. Mean values of SvO2, SvcO2 and SvaO2 were 72.20±8.26%, 74.61±7.60% and 74.64±8.47%. Linear correlation test showed a weak correlation between SvO2 and SvcO2 (r=0.61, p<0.0001) and also between SvO2 and SvaO2 (r=0.70, p<0.0001). Agreements between SvcO2/SvO2 and SvaO2/SvO2 were -2.40±1.96 (-16.20 and 11.40) and -2.40±1.96 (-15.10 and 10.20), respectively, with no difference in the cardiac output subgroups. No agreement was found in clinical management for 27.8% of the cases, both for SvcO2/SvO2 and for SvaO2/SvO2., Conclusion: This study showed that the correlation and agreement between SvO2 and SvcO2 is weak and may lead to different clinical management.

In order to study the infectious agents causing human disseminated cryptococcosis in the state of Pará, North Brazil, 56 isolates of Cryptococcusspp. (54 isolated from cerebral spinal fluid and two from blood cultures) from 43 cases diagnosed between 2003-2007 were analysed. The species were determined through morphological and physiological tests and genotypes were determined by URA5-RFLP and PCR-fingerprinting (wild-type phage M13). The following species and genotypes were identified: Cryptococcus neoformans VNI (28/56, 50%), Cryptococcus gattii VGII (25/56, 44.64%) and C. gattii VGI (3/56, 5.26%). The genotype VNI occurred in 12 out of 14 HIV-positive adults, whereas the genotype VGII occurred in 11 out of 21 HIV-negative adults (p < 0.02, OR = 6.6 IC95% 0.98-56.0). All patients less than 12 years old were HIV negative and six cases were caused by the VGII genotype, one by the VGI and one by VNI. Therefore, endemic primary mycosis in HIV-negative individuals, including an unexpectedly high number of children, caused by the VGII genotype deserves further study and suggests the need for surveillance on cryptococcal infection in the state of Pará, Eastern Amazon.

Context and Objective: Intrahospital transportation of mechanically ventilated patients is a high-risk situation. We aimed to determine whether transfers could be safely performed by using a transportation routine., Design and Setting: Prospective cohort study with 'before and after' evaluation., Methods: Mechanically ventilated patients who needed transportation were included. Hemodynamic and respiratory parameters were measured before and after transportation. Statistical analysis consisted of variance analysis and paired Student's t test. Results were considered significant if P < 0.05., Results: We studied 37 transfers of 26 patients (12 female) of mean age 46.6 +/- 15.7. Patients with pulmonary diseases, positive end expiratory pressure > 5, FiO2 > 0.4 and vasoactive drug use comprised 42.4%, 24.3%, 21.6% and 33.0% of cases, respectively. Mean duration of transportation was 43.4 +/- 18.9 minutes. Complications occurred in 32.4%. There was a significant increase in CO2 (before transportation, 29.6 +/- 7.3 and after transportation, 34.9 +/- 7.0; P = 0.000); a trend towards improved PO2/FiO2 ratio (before transportation, 318.0 +/- 137.0 and after transportation, 356.8 +/- 119.9; P = 0.053); increased heart rate (before transportation, 80.9 +/- 18.7 and after transportation, 85.5 +/- 17.6; P = 0.08); and no significant change in mean arterial blood pressure (P = 0.93)., Conclusion: These results suggest that intrahospital transportation can be safely performed. Our low incidence of complications was possibly related to both the presence of a multidisciplinary transportation team and proper equipment.

Objective: Abnormal responsiveness to arginine vasopressin (AVP) was previously observed in cortisol-producing adrenocortical tumours but the mechanism remains unclear. The aim of this study was to characterize the effect of AVP on cortisol secretion from adrenocortical tumours compared to normal human adrenal gland., Design: A multicentre study based on pharmacological, molecular and immunohistochemical experiments performed in adenomatous and normal adrenal tissues., Patients: Twenty patients with adrenocortical adenomas and subclinical Cushing's syndrome (SCCS) or Cushing's syndrome (CS) were compared to six control normal subjects., Measurements: In vivo and in vitro cortisol response to vasopressin, vasopressin receptor subtype mRNA measurement by real-time polymerase chain reaction (RT-PCR), immunohistochemical localization of AVP and its V1a receptor in tumour and normal adrenal tissues., Results: Terlipressin in vivo enhanced cortisol plasma levels in 17/20 SCCS and 3/6 CS but in none of the control subjects. In vitro cortisol response to AVP was observed in nine tumours studied, with enhanced efficacy and/or potency of AVP in three SCCS tumours compared to normal tissues. AVP receptor subtype mRNA levels were similar in SCCS, CS cells and normal adrenal cells. Some SCCS tumour steroidogenic cells showed AVP and V1a receptor immunoreactivity., Conclusions: SCCS and CS adrenocortical tumours often exhibit in vivo and in vitro hyper-responsiveness to AVP, which is not related to vasopressin receptor overexpression, but may be explained by more efficient coupling pathways or by the indirect action of AVP through an autocrine/paracrine mechanism.

Background and Objectives: Total knee arthroplasty (TKA) causes severe tissue trauma, leading to severe postoperative pain. Good postoperative analgesia is fundamental and one should consider that early mobilization of the joint is an important aspect to obtain good results. There is a controversy in the literature on the efficacy of isolated femoral nerve block. The objective of this study was to evaluate postoperative analgesia with the association of sciatic and femoral nerve block., Methods: Seventeen patients undergoing TKA under spinal anesthesia were divided in two groups: A and B. In Group A (n = 9), femoral nerve block was performed, while in Group B (n = 8), femoral and sciatic nerve block were done. The blockades were done in the immediate postoperative period with 20 mL of 0.5% of ropivacaine. Pain was evaluated in the first 24 hours using the Visual Analog Scale and the verbal scale. The length of time between the nerve block and the first complaint of pain (M1) was also evaluated., Results: The median of the duration of analgesia (M1) in Group A was 110 min, while in Group B it was 1285 min (p = 0.0001). There were no complications related to the technique used., Conclusions: Sciatic nerve block, when associated with femoral nerve block, under the conditions of the present study, improved significantly the quality of postoperative analgesia in TKA.

We have previously shown that the endozepine octadecaneuropeptide (ODN) stimulates the biosynthesis of neurosteroids from frog hypothalamic explants. In the present study, we have investigated the structure-activity relationships of a series of analogs of the C-terminal octapeptide of ODN (OP) on neurosteroid formation. We found that OP and its cyclic analog cyclo1-8OP stimulate in a concentration-dependent manner the synthesis of various steroids including 17-hydroxypregnenolone, progesterone, 17-hydroxyprogesterone and dehydroepiandrosterone. Deletion or Ala-substitution of the Arg1 or Pro2 residues of OP did not affect the activity of the peptide. In contrast, deletion or replacement of any of the amino acids of the C-terminal hexapeptide fragment totally abolished the effect of OP on neurosteroid biosynthesis. The present study indicates that the C-terminal hexapeptide of ODN/OP is the minimal sequence retaining full biological activity on steroid-producing neurons.

Objective: Early tracheal extubation following surgical procedures favors clinical evolution of patients and reduces incidence and time of stay in the Intensive Care Unit (ICU), minimizing hospital costs. Immediate postoperative period of pulmonary resections often takes place in the ICU and patients are kept intubated. This study evaluated hospital records of patients submitted to thoracotomy and a correlation between extubation time, postoperative evolution and ICU stay was established., Methods: Retrospective cohort study of records of 121 patients submitted to pulmonary parenchyma resection (not biopsies) was carried out. Stay in the ICU and time of tracheal extubation were related. Postoperative evolution was classified as good or bad according to occurrence of some of the following conditions: infections, respiratory disorders (reintubation, bronchospasm, acute pulmonary edema, need of tracheotomy, atelectasis, fistulae), re-operation due to bleeding and death. Among the two groups preoperative conditions, anesthetic physical status (American Society of Anesthesiologists--ASA criteria), presence of associated diseases, respiratory functional evaluation and duration of surgery were analyzed. Relative risk was used to evaluate effect of time of extubation (immediate or non-immediate) on the postoperative evolution of patients., Results: Patient distribution related to extubation time was: 81% immediate extubation, 15% non-immediate extubation and 4% not extubated. Destination after surgery was: 73% ICU and 27% post-anesthetic recovery room. Incidence of associated diseases (arterial hypertension, diabetes, obstructive or restrictive pulmonary disease and cardiopathy) among the immediately extubated group and non-immediately extubated group was 37% and 41.6%, respectively. Related to ASA physical status: 62% ASA 1 or 2 in the immediately extubated group and 58.3% ASA 1 or 2 in the non- immediately extubated group. Surgical time was (mean +/- standard deviation) 372.34 +/- 107.84 minutes and 432.61 +/- 117.30 minutes in immediately extubated and non- immediately extubated group, respectively. Relative risk of immediate extubation leading to a poor evolution was of 0.81, while non- immediate extubation leading to a poor evolution was of 1.5., Conclusions: Safe immediate tracheal extubation of patients submitted to pulmonary resection surgery is possible. This kind of management favors postoperative recuperation out of ICU, which results in patients and hospital benefits, mainly referred to costs.

Background: The anesthetic halothane can be reductively metabolized to reactives intermediates that may initiate lipid peroxidation accompanied by hepatic injury. Hypoxia and phenobarbital pretreatment in rats increases metabolism of halothane, the oxidative stress, cause liver antioxidant enzymes changes and tissue damage., Aims: We investigated the effect of halothane on hepatic lipid peroxidation and on hepatic histology after increases reductive metabolism of halothane caused by hypoxia and phenobarbital pretreatment., Methods: Twenty-five male wistar rats were divided in five equals groups: CO (Control), HO14 (Halothane/Hypoxia), F (fenobarbital alone), O14 (Hypoxia alone) and H (Halothane alone). After 24 hours the rats were killed, their livers removed to determine chemoluminescence, thiobarbituric acid-reactive substances, catalase, superoxide dismutase, and blood samples were taken to determine AST and ALT. The histopathologic evaluation was performed with hematoxylin and eosin staining. Histopathologic scores are presented as 25th-75th percentile/range values and median +/- range., Results/conclusion: Halothane-hypoxic exposure resulted in a significant changes in the activities of antioxidant enzymes, and induced hepatic lipoperoxidation. Moreover it resulted in histopathologic liver injury as well as significant increase of serum activity of AST and ALT.