Utilizing Artificial Intelligence and Chat Generative Pretrained Transformer to Answer Questions About Clinical Scenarios in Neuroanesthesiology.

OBJECTIVE: We tested the ability of chat generative pretrained transformer (ChatGPT), an artificial intelligence chatbot, to answer questions relevant to scenarios covered in 3 clinical guidelines, published by the Society for Neuroscience in Anesthesiology and Critical Care (SNACC), which has published management guidelines: endovascular treatment of stroke, perioperative stroke (Stroke), and care of patients undergoing complex spine surgery (Spine). METHODS: Four neuroanesthesiologists independently assessed whether ChatGPT could apply 52 high-quality recommendations (HQRs) included in the 3 SNACC guidelines. HQRs were deemed present in the ChatGPT responses if noted by at least 3 of the 4 reviewers. Reviewers also identified incorrect references, potentially harmful recommendations, and whether ChatGPT cited the SNACC guidelines. RESULTS: The overall reviewer agreement for the presence of HQRs in the ChatGPT answers ranged from 0% to 100%. Only 4 of 52 (8%) HQRs were deemed present by at least 3 of the 4 reviewers after 5 generic questions, and 23 (44%) HQRs were deemed present after at least 1 additional targeted question. Potentially harmful recommendations were identified for each of the 3 clinical scenarios and ChatGPT failed to cite the SNACC guidelines. CONCLUSIONS: The ChatGPT answers were open to human interpretation regarding whether the responses included the HQRs. Though targeted questions resulted in the inclusion of more HQRs than generic questions, fewer than 50% of HQRs were noted even after targeted questions. This suggests that ChatGPT should not currently be considered a reliable source of information for clinical decision-making. Future iterations of ChatGPT may refine algorithms to improve its reliability as a source of clinical information.

Injectable Adhesive Hydrogels for Soft tissue Reconstruction: A Materials Chemistry Perspective.

Injectable bioadhesives offer several advantages over conventional staples and sutures in surgery to seal and close incisions or wounds. Despite the growing research in recent years few injectable bioadhesives are available for clinical use. This review summarizes the key chemical features that enable the development and improvements in the use of polymeric injectable hydrogels as bioadhesives or sealants, their design requirements, the gelation mechanism, synthesis routes, and the role of adhesion mechanisms and strategies in different biomedical applications. It is envisaged that developing a deep understanding of the underlying materials chemistry principles will enable researchers to effectively translate bioadhesive technologies into clinically-relevant products.

Sex Hormones, Metabolic Status, and Obesity in Female Patients with Acne Vulgaris Along with Clinical Correlation: An Observational Cross-Sectional Study.

BACKGROUND: Acne vulgaris is a common dermatological disorder. Several hormones are suspected to play a role in its etiopathogenesis. AIMS AND OBJECTIVES: The aim of this study was to analyze the role of sex-hormones, metabolic status, and obesity in acne vulgaris and correlate with its severity and symptom load. MATERIALS AND METHODS: This cross-sectional observational study included 89 female patients with acne vulgaris and certain phenotypic markers such as prepubertal onset, late-onset, persistent course, hirsutism, acanthosis nigricans, acrochordons, premenstrual flare, and diminished response to isotretinoin; suggestive of an underlying hormonal pathology. All patients were subjected to physical examination to rule out obesity and metabolic syndrome along with serum biochemistry to detect sex hormones (testosterone, progesterone, estrogen), serum insulin and insulin resistance (HOMA-IR) and lipid profile. RESULTS: Among 89 patients (mean age 21.3 ± 5.3 years), 34.8% presented with late-onset/persistent/pre-pubertal acne, 33.7% presented with premenstrual flare and 28.2% presented with hirsutism. Hormonal analysis revealed elevated testosterone and progesterone with low estrogen across all categories of patients. Testosterone was significantly elevated even in mild acne. Serum lipid profile was altered significantly only in hirsute females. In total, 36% and 20.2% patients presented with metabolic syndrome and obesity, respectively; however, neither was associated with severity of acne. CONCLUSION: Sex-hormones, serum lipids, metabolic status, and body mass index are altered in acne vulgaris. All acne patients with endocrine markers should be evaluated for sex-hormones irrespective of severity and symptom load, whereas hirsutism may be regarded as clinical marker of lipid abnormalities. Metabolic syndrome and obesity do not seem to be directly correlated with acne severity. Thus, anti-androgens may be considered as adjuvant therapy in these patients, not responding to conventional therapy.

Biologically active polysaccharide from edible mushrooms: A review.

Mushrooms are renewable natural gift for humankind, furnished with unique taste, flavor and medicinal properties. For the last few decades study of mushroom polysaccharides has become a matter of great interest to the researchers for their immunomodulating, antimicrobial, antioxidant, anticancer, and antitumor properties. Molecular mass, branching configuration, conformation of polysaccharides and chemical modification are the major factors influencing their biological activities. The mechanism of action of mushroom polysaccharides is to stimulate T-cells, B-cells, natural killer cells, and macrophage dependent immune responses via binding to receptors like the toll-like receptor-2, dectin-1. The present review offers summarized and significant information about the structural and biological properties of mushroom polysaccharides, and their potential for development of therapeutic materials.

Structural studies of immunomodulatory (1 → 3)-, (1 → 4)-α glucan from an edible mushroom Polyporus grammocephalus.

A water soluble polysaccharide (PGPS) with molecular weight ~ 1.4 × 105 Da was isolated by alkali treatment from an edible mushroom Polyporus grammocephalus and purified by gel chromatography using sepharose-6B column. Monosaccharide analysis revealed that PGPS was made up of glucose only. PGPS contained (1 â†’ 3)-α-D-Glcp and (1 â†’ 4)-α-D-Glcp moieties in a molar ratio of nearly 1:2. Through a series of chemical and spectroscopic (1D/2D NMR) investigations, the repeating unit of the glucan was established as: →3)-α-D-Glcp(1 â†’ [4)-α-D-Glcp(1]2→ This α-glucan was observed to stimulate some prime components of immune system, namely, macrophages, splenocytes, and thymocytes.

Polymers and Composites Derived from Castor Oil as Sustainable Materials and Degradable Biomaterials: Current Status and Emerging Trends.

Recent years have seen rapid growth in utilizing vegetable oils to derive a wide variety of polymers to replace petroleum-based polymers for minimizing environmental impact. Nonedible castor oil (CO) can be extracted from castor plants that grow easily, even in an arid land. CO is a promising source for developing several polymers such as polyurethanes, polyesters, polyamides, and epoxy-polymers. Several synthesis routes have been developed, and distinct properties of polymers have been studied for industrial applications. Furthermore, fillers and fibers, including nanomaterials, have been incorporated in these polymers for enhancing their physical, thermal, and mechanical properties. This review highlights the development of CO-based polymers and their composites with attractive properties for industrial and biomedical applications. Recent advancements in CO-based polymers and their composites are presented along with a discussion on future opportunities for further developments in diverse applications.

Therapeutic Potential of Two Visible Light Responsive Luminescent photoCORMs: Enhanced Cellular Internalization Driven by Lipophilicity.

Herein we report the synthesis, characterization, and cellular internalization properties of two visible-light active luminescent Mn-based photoCORMs. The enhanced membrane permeability of the photoactive Mn carbonyl complex (photoCORM) derived from a designed lipophilic ligand namely, [Mn(CO)3(Imdansyl)(L1)](CF3SO3) (1) (where L1 = a diazabutadiene-based ligand containing two highly lipophilic adamantyl motifs, Imdansyl = dansylimidazole) promoted rapid internalization within human colorectal adenocarcinoma (HT-29) cells compared to [Mn(CO)3(Imdansyl)(L2)](CF3SO3) (2) (where L2 = a diazabutadiene ligand bearing two hydrophilic 1,3,5-triazaadamantyl group). Colocalization experiments using membrane stain indicate different extents of localization of the two CO complexes within the cellular matrix. Visible-light triggered CO release from the lipophilic photoCORM induced caspase-3/7 activation on HT-29 cells, which was detected using confocal microscopy. The rapid accumulation of the lipophilic photoCORM 1 in the cellular membrane resulted in more efficient CO-induced cell death compared to the hydrophilic analogue 2.

Spontaneous Resolution by Crystallization of an Octanuclear Iron(III) Complex Using Only Racemic Reagents.

The P and M enantiomers of the octanuclear [Fe8 (µ4 -O)4 (µ-4-Cl-pz)12 Cl4 ] complex, having T symmetry, were resolved by temporary substitution of chloride ligands by racemic 4-s Bu-phenolates and subsequent crystallization, where the (S)- and (R)-phenolates coordinate selectively to the M and P complexes, respectively. The complexes were characterized by circular dichroism analysis and X-ray structure determination. This work constitutes a rare example of enantiomeric recognition resulting in spontaneous resolution upon crystallization.

Magnetic resonance imaging contrast enhancement in vitro and in vivo by octanuclear iron-oxo cluster-based agents.

A water-soluble octanuclear cluster, [Fe8], was studied with regard to its properties as a potential contrast enhancing agent in magnetic resonance imaging (MRI) in magnetic fields of 1.3, 7.2 and 11.9 T and was shown to have transverse relaxivities r2 = 4.01, 10.09 and 15.83 mM s-1, respectively. A related hydrophobic [Fe8] cluster conjugated with 5 kDa hyaluronic acid (HA) was characterized by 57Fe-Mössbauer and MALDI-TOF mass spectroscopy, and was evaluated in aqueous solutions in vitro with regard to its contrast enhancing properties [r2 = 3.65 mM s-1 (1.3 T), 26.20 mM s-1 (7.2 T) and 52.18 mM s-1 (11.9 T)], its in vitro cellular cytotoxicity towards A-549 cells and COS-7 cells and its in vivo enhancement of T2-weighted images (4.7 T) of a human breast cancer xenografted on a nude mouse. The physiologically compatible [Fe8]-HA conjugate was i.v. injected to the tumor-bearing mouse, resulting in observable, heterogeneous signal change within the tumor, evident 15 min after injection and persisting for approximately 30 min. Both molecular [Fe8] and its HA-conjugate show a strong magnetic field dependence on r2, rendering them promising platforms for the further development of T2 MRI contrast agents in high and ultrahigh magnetic fields.

A Luminescent Manganese PhotoCORM for CO Delivery to Cellular Targets under the Control of Visible Light.

A photoactive manganese carbonyl complex derived from dansylimidazole (Imdansyl), namely, [Mn(Imdansyl)(CO)3(phen)](CF3SO3) (1), has been synthesized and structurally characterized. This is the first luminescent manganese carbonyl-based photoCORM reported in the literature. This complex exhibits CO release under the exclusive control of low-power broadband visible light. The corresponding rhenium carbonyl complex, namely, [Re(Imdansyl)(CO)3(phen)](CF3SO3) (2), has also been reported, which is luminescent but sensitive only to UV-B (λ<315 nm) light. The entry of the manganese photoCORM into the human colorectal adenocarcinoma cells (HT-29) has been demonstrated with the aid of fluorescence microscopy. Irradiation of the photoCORM-loaded cancer cells to visible light leads to a dose-dependent apoptotic cell death.

Synthesis and structures of photoactive rhenium carbonyl complexes derived from 2-(pyridin-2-yl)-1,3-benzothiazole, 2-(quinolin-2-yl)-1,3-benzothiazole and 1,10-phenanthroline.

Carbon monoxide (CO) has recently been identified as a gaseous signaling molecule that exerts various salutary effects in mammalian pathophysiology. Photoactive metal carbonyl complexes (photoCORMs) are ideal exogenous candidates for more controllable and site-specific CO delivery compared to gaseous CO. Along this line, our group has been engaged for the past few years in developing group-7-based photoCORMs towards the efficient eradication of various malignant cells. Moreover, several such complexes can be tracked within cancerous cells by virtue of their luminescence. The inherent luminecscent nature of some photoCORMs and the change in emission wavelength upon CO release also provide a covenient means to track the entry of the prodrug and, in some cases, both the entry and CO release from the prodrug. In continuation of the research circumscribing the development of trackable photoCORMs and also to graft such molecules covalently to conventional delivery vehicles, we report herein the synthesis and structures of three rhenium carbonyl complexes, namely, fac-tricarbonyl[2-(pyridin-2-yl)-1,3-benzothiazole-κ2N,N'](4-vinylpyridine-κN)rhenium(I) trifluoromethanesulfonate, [Re(C7H7N)(C12H8N2S)(CO)3](CF3SO3), (1), fac-tricarbonyl[2-(quinolin-2-yl)-1,3-benzothiazole-κ2N,N'](4-vinylpyridine-κN)rhenium(I) trifluoromethanesulfonate, [Re(C7H7N)(C16H10N2S)(CO)3](CF3SO3), (2), and fac-tricarbonyl[1,10-phenanthroline-κ2N,N'](4-vinylpyridine-κN)rhenium(I) trifluoromethanesulfonate, [Re(C7H7N)(C12H8N2)(CO)3](CF3SO3), (3). In all three complexes, the ReI center resides in a distorted octahedral coordination environment. These complexes exhibit CO release upon exposure to low-power UV light. The apparent CO release rates of the complexes have been measured to assess their comparative CO-donating capacity. The three complexes are highly luminescent and this in turn provides a convenient way to track the entry of the prodrug molecules within biological targets.

Eradication of HT-29 colorectal adenocarcinoma cells by controlled photorelease of CO from a CO-releasing polymer (photoCORP-1) triggered by visible light through an optical fiber-based device.

The gaseous signaling molecule carbon monoxide (CO) has recently been recognized for its wide range of physiological activity as well as its antineoplastic properties. However, site-specific delivery of this noxious gas presents a major challenge in hospital settings. In this work, a visible light-sensitive CO-releasing molecule (photoCORM) derived from manganese(I) and 2-(quinolyl)benzothiazole (qbt) namely, [Mn(CO)3(qbt)(4-vpy)](CF3SO3) (1), has been co-polymerized within a gas-permeable HEMA/EGDMA hydrogel. The resulting photoactive CO-releasing polymer (photoCORP-1) incorporates 1 such that neither the carbonyl complex nor its photoproduct(s) exits the polymer at any time. The material can be triggered to photorelease CO remotely by low-power broadband visible light (<1mWcm-2) with the aid of fiber optics technology. The CO photorelease rates of photoCORP-1 (determined by spectrophotometry) can be modulated by both the concentration of 1 in the hydrogel and the intensity of the light. A CO-delivery device has been assembled to deliver CO to a suspension of human colorectal adenocarcinoma cells (HT-29) under the control of visible light and the extent of CO-induced apoptotic death of the cancer cells has been determined via Annexin V/Propidium iodide stain and flow cytometry. This photoactive CO-releasing polymer could find use in delivering controlled doses of CO to cellular targets such as malignant tissues in remote parts of the body.

CO-Induced apoptotic death of colorectal cancer cells by a luminescent photoCORM grafted on biocompatible carboxymethyl chitosan.

A photo-active luminescent rhenium carbonyl complex namely, [Re(CO)3(phen)(pyAl)](CF3SO3) was grafted on a biocompatible carboxymethyl chitosan (CMC) matrix through Schiff base condensation reaction. The light-induced CO delivery from ReCMC has been shown to eradicate human colorectal adenocarcinoma cells (HT-29) very efficiently in a dose-dependent fashion. The onset of CO-induced apoptosis was realized by caspase-3,-7 detection aided by fluorescence confocal microscopy. ReCMC represents a unique example of a biocompatible and biodegradable antineoplastic agent that could find its use in cancer photopharmacology.

Luminescent Re(I) Carbonyl Complexes as Trackable PhotoCORMs for CO delivery to Cellular Targets.

A family of Re(I) carbonyl complexes of general formula [ReX(CO)3(phen)]0/1+ (where X = Cl-, CF3SO3-, MeCN, PPh3, and methylimidazole) derived from 1,10-phenanthroline (phen) exhibits variable emission characteristics depending on the presence of the sixth ancillary ligand/group (X). All complexes but with X = MeCN exhibit moderate CO release upon irradiation with low-power UV light and are indefinitely stable in anaerobic/aerobic environment in solution as well as in solid state when kept under dark condition. These CO donors liberate three, one, or no CO depending on the nature of sixth ligand upon illumination as studied with the aid of time-dependent IR spectroscopy. Results of excited-state density functional theory (DFT) and time-dependent DFT calculations provided insight into the origin of the emission characteristics of these complexes. The luminescent rheinum(I) photoCORMs uniformly displayed efficient cellular internalization by the human breast adenocarcinoma cells, MDA-MB-231, while the complex with PPh3 as ancillary ligand showed moderate nuclear localization in addition to the cytosolic distribution. These species hold significant promise as theranostic photoCORMs (photoinduced CO releasing molecules), where the entry of the pro-drug can be tracked within the cellular matrices.

Synthesis, Structures, and CO Release Capacity of a Family of Water-Soluble PhotoCORMs: Assessment of the Biocompatibility and Their Phototoxicity toward Human Breast Cancer Cells.

Two manganese(I) carbonyl complexes derived from 2-(pyridyl)benzothiazole (pbt) and 1,10-phenanthroline (phen) release carbon monoxide (CO) under low-power broad-band visible-light illumination. CO photorelease from [Mn(CO)3(pbt)(PTA)]CF3SO3 (1, where PTA = 1,3,5-triaza-7-phosphaadamantane) is accompanied by an emergence of a strong fluorescence around 400 nm from almost nonfluorescent preirradiated 1. However, [Mn(CO)3(phen)(PTA)]CF3SO3 (2) showed no such phenomenon upon prolonged illumination under similar experimental conditions. The two analogous rhenium(I) complexes, namely, [Re(CO)3(pbt)(PTA)]CF3SO3 (3) and [Re(CO)3(phen)(PTA)]CF3SO3 (4), have also been synthesized and characterized to compare their photo properties with the manganese congeners. Complexes 3 and 4 exhibit moderate CO release upon irradiation with low-power UV light. All four complexes are highly soluble in anaerobic/aerobic aqueous media and are also considerably more stable when kept under dark conditions. The inherently luminescent rhenium complex 3 was utilized to demonstrate cellular internalization of these types of compounds by MDA-MB-231 (human breast cancer) cells, while the two biocompatible manganese(I) complexes (1 and 2) have been applied to assess the cell viability of these malignant cells upon CO delivery.

A Theranostic Two-Tone Luminescent PhotoCORM Derived from Re(I) and (2-Pyridyl)-benzothiazole: Trackable CO Delivery to Malignant Cells.

A Re(I) carbonyl complex derived from 2-(2-pyridyl)-benzothiazole (pbt), [Re(H2O)(CO)3(pbt)](CF3SO3) (1), rapidly releases CO under low-power UV illumination. CO photorelease from 1 is accompanied by a change in luminescence from orange to deep blue. These two distinct luminescence signals have been successfully employed to track (a) the entry of the pro-drug 1 into cancer cells and (b) the end of the CO (drug) delivery step within the target.

Synthesis and Characterization of a "Turn-On" photoCORM for Trackable CO Delivery to Biological Targets.

A designed photoactive CO releasing molecule (photoCORM), namely, fac-[MnBr(CO)3(pbt)] (1, pbt = 2-(2-pyridyl)benzothiazole), promotes CO-induced death of MDA-MB-231 human breast cancer cells upon illumination with broadband visible light. The CO release from this photoCORM can be tracked by rise in fluorescence within the cellular matrix due to deligation of the pbt ligand. The results of this study suggest the potential of 1 in eradication of cancer cells through CO delivery.

Diagnostic and prognostic significance of different mucin expression, preoperative CEA, and CA-125 in colorectal carcinoma: A clinicopathological study.

BACKGROUND: Colorectal carcinoma (CRC) is the fourth most commonly diagnosed malignant disease worldwide, with over 1 million new cases and approximately 5,00,000 deaths each year. AIMS AND OBJECTIVES: This prospective observational study was done to study the clinicopathological characteristics of CRC including mucin stains and correlate the preoperative serum carcinoembryonic antigen (CEA) and cancer antigen (CA)-125 levels with the prognosis. MATERIALS AND METHODS: A total of 90 CRCs were included from December 2010 to June 2013. Detailed history and relevant clinical/radiological findings were noted in all clinically and/or radiologically suspected cases of CRC. Preoperative blood samples were collected for serum CEA and CA-125 level estimation. The mucin expression was evaluated with special stains. RESULTS: The combined Alcian blue-periodic acid Schiff (PAS) staining was positive for both stains in 68.88% cases indicating that both neutral and acidic mucins are increased in CRC. High preoperative serum CEA levels were seen in 82.22% cases, whereas preoperative serum CA-125 levels showed an increase in 20% cases. Higher levels of these tumor markers corresponded with higher TNM stage. CONCLUSIONS: Mucin evaluation in CRCs remains one of the valuable methods as mucinous variants correlate with worse prognosis. Preoperative serum CEA level assessment is an indispensible adjunct to the diagnosis and prognosis of CRC. However, preoperative serum CA-125 level measurement is not an efficient tool for prognostication in CRC and should not be recommended for routine use.

Rapid CO release from a Mn(I) carbonyl complex derived from azopyridine upon exposure to visible light and its phototoxicity toward malignant cells.

Two Mn(I) carbonyl complexes namely [MnBr(azpy)(CO)3] and [Mn(azpy)(CO)3(PPh3)](ClO4) (azpy = 2-phenylazopyridine) have been synthesized and characterized. Both complexes exhibit rapid CO release upon exposure to low power visible light. [MnBr(azpy)(CO)3] shows significant phototoxicity toward two malignant cell lines HeLa and MDA-MB-231.

Water-Soluble Derivatives of Octanuclear Iron-Oxo-Pyrazolato Complexes; An Experimental and Computational Study.

Two water-soluble iron-pyrazolato complexes, [Fe8], have been prepared by the introduction of twelve hydroxyalkyl groups to the periphery of the approximately spherical octanuclear molecule and they are contrasted with their two organosoluble chloroalkyl analogues. All four new complexes, 1 - 4, have been characterized in solution by 1H-NMR and electrospray ionization mass spectroscopy. The one-electron reduction product of the water-soluble 3, [Fe8]-, has been structurally characterized by single crystal diffraction methods. In aqueous media, the four terminal Fe-Cl bonds of [Fe8] are partially hydrolysed and the resulting chloro/aqua/hydroxo species form supramolecular nanoscale aggregates, as determined by dynamic light scattering and electron microscopy. Preliminary computational studies by density functional theory methods have been employed in order to model the H-bonding interactions controlling the competing solvation and aggregation processes.