Automated radiosynthesis of mGluR5 PET tracer [18F]FPEB from aryl-chloro precursor and validation for clinical application.

The radioligand [18F]FPEB, used for PET imaging of the brain's metabotropic glutamate receptor subtype 5 (mGluR5), undergoes a thorough validation process to ensure its safety, efficacy, and quality for clinical use. The process starts by optimizing the synthesis of [18F]FPEB to achieve high radiochemical yield and purity. This study focuses on optimizing the radiolabeling process using an aryl-chloro precursor and validating the GMP production for clinical applications. Fully automated radiolabeling was achieved via one-step nucleophilic substitution reaction. [18F]FPEB was produced and isolated in high radioactivity and radiochemical purity. Throughout the validation process, thorough quality control measures are implemented. Radiopharmaceutical batch release criteria are established, including testing for physical appearance, filter integrity, pH, radiochemical purity, molar activity, radiochemical identity, chemical impurity, structural identity, stability, residual solvent, sterility, and endotoxin levels. In conclusion, the validation of [18F]FPEB involved a comprehensive process of synthesis optimization, quality control, which ensure the safety, efficacy, and quality of [18F]FPEB, enabling its reliable use in clinical PET. Here, we successfully radiolabeled and validated [18F]FPEB using aryl-chloro precursor according to GMP production for clinical application.

Design of a Liquid Impregnated Surface with a Stable Lubricant Layer in a Mixed Water/Oil Environment for Low Hydrate Adhesion.

Clathrate hydrate is a naturally occurring icelike solid that forms in the water phase under suitable temperature and pressure conditions in the presence of one or more hydrophobic molecules. It also forms inside the oil and gas pipes, leading to higher pumping cost, flow blockage, and even catastrophic accidents. Engineered surfaces with low hydrate adhesion can provide an effective solution to this problem. Liquid impregnated surfaces are examples of engineered surfaces that have already shown tremendous potential for reducing the nucleation and adhesion of solids. Here, we report the design and synthesis of liquid impregnated surfaces with extremely low hydrate adhesion under an oil and water mixed environment. The most challenging aspect of designing these surfaces was to stabilize a lubricant layer simultaneously under water and oil. A detailed methodology to make such lubricant-stable surfaces from a theoretical perspective was described and experimentally validated for lubricant stability. Experimental measurements on such surfaces showed extremely low hydrate accumulation and 1 order of magnitude or more reduction in hydrate adhesion force.

Visiblelight-induced ternary electron donor-acceptor complex enabled synthesis of 2-(2-hydrazinyl) thiazole derivatives and the assessment of their antioxidant and antidiabetic therapeutic potential.

A mild and eco-friendly visible-light-induced synthesis of 2-(2-hydrazinyl) thiazole from readily accessible thiosemicarbazide, carbonyl, and phenacyl bromide in the absence of a metal catalyst and/or any extrinsic photosensitizer is reported. This approach only requires a source of visible light and a green solvent at room temperature to produce the medicinally privileged scaffolds of hydrazinyl-thiazole derivatives in good to outstanding yields. Experimental studies support the in situ formation of a visible-light-absorbing, photosensitized colored ternary EDA complex. The next step is to prepare a pair of radicals in an excited state, which makes it easier to prepare thiazole derivatives through a SET and PCET process. DFT calculations additionally supported the mechanistic analysis of the course of the reaction. The antioxidant and antidiabetic properties of some of the compounds in the synthesized library were tested in vitro. All the investigated compounds demonstrated appreciable antioxidant activity, as evidenced by the reducing power experiment and the IC50 values of the DPPH radical scavenging experiment. Furthermore, the IC50 values for 4c, 4d, and 4g also demonstrated a strong α-amylase inhibitory effect.

Synthesis of Cu (II) and Zn (II) Complexes of a Quinoline Based Flexible Amide Receptor as Fluorescent Probe for Dihydrogen Phosphate and Hydrogen Sulphate and Their Antibacterial Activity.

A novel 8-hydroxy quinoline-derived amide receptor, in conjunction with its Cu (II) and Zn (II) complexes, has been strategically developed to function as remarkably efficient fluorescent receptors with a distinct capability for anion sensing. The comprehensive characterization of the synthesized compounds were achieved through UV-Vis, IR, NMR, and HRMS spectroscopic techniques. Among the Cu (II) and Zn (II) complexes, the latter exhibits superior selectivity for anions, specifically dihydrogen phosphate and hydrogen sulfate, as their tetrabutylammonium salts in a 9:1 acetonitrile-water (v/v) mixture. The Cu (II) complex demonstrates enhanced anion binding compared to the amide ligand, albeit with reduced selectivity. Furthermore, the affinity was evaluated using the Benesi-Hildebrand plot. The binding constants and Limit of Detection (LOD) for both complexes were precisely quantified. The Job plot illustrates a clear 1:1 binding interaction between the metal complexes and the guest anions. Significantly, both metal-complex receptors display a broad spectrum of antibacterial activity, against both gram-positive and gram-negative bacteria. It is worth highlighting that the Zn (II) complexed receptor outperforms the Cu (II) complexed receptor, as evidenced by its considerably lower Minimum Inhibitory Concentration (MIC) value against both bacterial strains.

Endoscopic vs microscopic facial nerve decompression for traumatic facial nerve palsy: a randomized controlled trial.

PURPOSE: To explore a minimally invasive trans-canal endoscopic facial nerve decompression for traumatic facial nerve palsy and compare it with microscopic facial nerve decompression. METHODS: 35 and 38 patients underwent endoscopic and microscopic facial nerve decompression, respectively, for traumatic facial nerve palsy. Onset of symptoms, type of temporal bone fracture, day of surgical intervention following trauma, ossicular chain status and nature of insult to facial nerve were observed. Time period for recovery (House Brackmann grade ≤ 3), long term recovery rates, pre- and post-operative hearing status, surgical time and post-operative pain were compared between groups. RESULTS: Maximum patients in endoscopic and microscopic groups (77.1% and 76.3%, respectively) had acute onset of symptoms. 57.1% (20/35) had longitudinal, 17.1% (6/35) had transverse and 25.7% (9/35) had mixed fractures in endoscopic group. In the microscopic group, 57.9% (22/38) had longitudinal, 18.4% (7/38) had transverse and 23.7% (9/38) had mixed fractures. The mean (± S.D.) post-operative air-bone gap in endoscopic and microscopic group were 16.47 ± 4.5 dB and 19.4 ± 5.2 dB, respectively, which was statistically significant. The mean (± S.D.) time period for recovery of endoscopic and microscopic groups were 14.4 ± 5 days and 22.5 ± 7 days, respectively (p value < 0.05). The difference in post-operative pain between the two groups was also statistically significant. The difference in long term recovery rates was not statistically significant (p > 0.05). CONCLUSIONS: Endoscopic facial nerve decompression results in early recovery, less post-operative pain and better post-operative air-bone gap closure when compared to conventional microscopic technique.

Maternal depression: Technology enabled self screening in real time.

The first step toward providing treatment, is getting the right diagnosis in real time; before it is too late. Without this, resource deployment may appear to be comparable to the scale and scope of the problem, while in reality it may just be a drop in the ocean. Maternal depression, during pregnancy is a debilitating risk to both the mother and the child, but the bigger problem is, it goes unnoticed, undetected, and therefore untreated. If mobile technology can be deployed to screen for depression in real time by the pregnant mother herself, it will go miles in creating a HOPE for health.

A machine learning approach for accurate and real-time DNA sequence identification.

BACKGROUND: The all-electronic Single Molecule Break Junction (SMBJ) method is an emerging alternative to traditional polymerase chain reaction (PCR) techniques for genetic sequencing and identification. Existing work indicates that the current spectra recorded from SMBJ experimentations contain unique signatures to identify known sequences from a dataset. However, the spectra are typically extremely noisy due to the stochastic and complex interactions between the substrate, sample, environment, and the measuring system, necessitating hundreds or thousands of experimentations to obtain reliable and accurate results. RESULTS: This article presents a DNA sequence identification system based on the current spectra of ten short strand sequences, including a pair that differs by a single mismatch. By employing a gradient boosted tree classifier model trained on conductance histograms, we demonstrate that extremely high accuracy, ranging from approximately 96 % for molecules differing by a single mismatch to 99.5 % otherwise, is possible. Further, such accuracy metrics are achievable in near real-time with just twenty or thirty SMBJ measurements instead of hundreds or thousands. We also demonstrate that a tandem classifier architecture, where the first stage is a multiclass classifier and the second stage is a binary classifier, can be employed to boost the single mismatched pair's identification accuracy to 99.5 %. CONCLUSIONS: A monolithic classifier, or more generally, a multistage classifier with model specific parameters that depend on experimental current spectra can be used to successfully identify DNA strands.

Comparative evaluation of sagittal condylar guidance obtained from a clinical method and with cone beam computed tomography in dentate individuals.

STATEMENT OF PROBLEM: Programming semiadjustable and fully adjustable articulators involves time-consuming clinical steps which can be avoided if an accurate radiographic method can accurately determine the condylar guidance angles. PURPOSE: The purpose of this clinical study was to compare the sagittal condylar guidance in dentate individuals as determined by a clinical method, protrusive interocclusal record, and a radiographic method, cone beam computed tomography. If the methods show a correlation, then cone beam computed tomography can be used as a time-saving method of programming an articulator for patients requiring a cone beam computed tomography scan. MATERIAL AND METHODS: A total of 40 participants (20 men and 20 women) within the 20 to 40 years age group were enrolled according to the inclusion and exclusion criteria. Cone beam computed tomography scans were obtained, and by using an appropriate software program, the sagittal condylar guidance was measured for both sides. A protrusive interocclusal record was obtained by using polyvinyl siloxane material. The maxillary cast of each participant was mounted on a semiadjustable articulator with a facebow transfer, and the mandibular cast was mounted with a maximum intercuspal record. The protrusive record was then transferred to the articulator for programming. RESULTS: The right and left sagittal condylar guidance values obtained from both the protrusive interocclusal record and cone beam computed tomography method were comparable, with no significant differences (P>.05). The difference in condylar inclination values for both sexes obtained from both methods for both sides were not statistically different (P>.05). With increasing age, condylar inclination values obtained from both methods tended to decrease. The values for sagittal condylar guidance obtained from both methods (protrusive interocclusal record and cone beam computed tomography) were comparable and correlated. CONCLUSIONS: Cone beam computed tomography measurement involves stable bony landmarks and can be standardized, whereas clinical methods are time consuming and can provide inaccurate results because of the instability of the materials used to register the maxillomandibular relationship. Thus, cone beam computed tomography can be used to obtain the sagittal horizontal guidance for programming semiadjustable and fully adjustable articulators for patients requiring a cone beam computed tomography scan.

Impediment to growth and yeast-to-hyphae transition in Candida albicans by copper oxide nanoparticles.

The effects of two prominent copper oxide nanoparticles (CuO-NP and Cu2O-NP), with the oxidation state of Cu++ (cupric) and Cu+ (cuprous), on Candida albicans were evaluated. CuO-NP and Cu2O-NP were synthesized and characterized by XRD, FESEM, HR-TEM and Zeta potential. At sub-MIC (50 µg ml-1), both cupric and cuprous oxide NPs prevented yeast-to-hyphae switching and wrinkling behaviour in C. albicans. The mechanism for the antifungal action of the two NPs differed; CuO-NP significantly elicited reactive oxygen species, whereas membrane damage was more pronounced with Cu2O-NP. Real time PCR analysis revealed that CuO-NP suppressed the morphological switching of yeast-to-hyphae by down-regulating cph1, hst7 and ras1 and by up-regulation of the negative regulator tup1. In comparison, Cu2O-NP resulted in down-regulation of ras1 and up-regulation of the negative regulators nrg1 and tup1. Between the two NPs, CuO exhibited increased antifungal activity due to its stable oxidation state (Cu++) and its smaller dimensions compared with Cu2O-NP.

USP9X counteracts differential ubiquitination of NPHP5 by MARCH7 and BBS11 to regulate ciliogenesis.

Ciliogenesis is a fundamental biological process central to human health. Precisely how this process is coordinated with the cell cycle remains an open question. We report that nephrocystin-5 (NPHP5/IQCB1), a positive regulator of ciliogenesis, is a stable and low turnover protein subjected to cycles of ubiquitination and deubiquitination. NPHP5 directly binds to a deubiquitinating enzyme USP9X/FAM and two E3 ubiquitin ligases BBS11/TRIM32 and MARCH7/axotrophin. NPHP5 undergoes K63 ubiquitination in a cell cycle dependent manner and K48/K63 ubiquitination upon USP9X depletion or inhibition. In the G0/G1/S phase, a pool of cytoplasmic USP9X recruited to the centrosome by NPHP5 protects NPHP5 from ubiquitination, thus favouring cilia assembly. In the G2/M phase, USP9X dissociation from the centrosome allows BBS11 to K63 ubiquitinate NPHP5 which triggers protein delocalization and loss of cilia. BBS11 is a resident centrosomal protein, whereas cytoplasmic USP9X sequesters the majority of MARCH7 away from the centrosome during interphase. Depletion or inhibition of USP9X leads to an accumulation of centrosomal MARCH7 which K48 ubiquitinates NPHP5, triggering protein degradation and cilia loss. At the same time, BBS11 K63 ubiquitinates NPHP5. Our data suggest that dynamic ubiquitination and deubiquitination of NPHP5 plays a crucial role in the regulation of ciliogenesis.

Two-drape closed pocket technique: minimizing aerosolization in mastoid exploration during COVID-19 pandemic.

BACKGROUND: Mastoidectomy is associated with extensive bone-drilling which makes it a major aerosol generating procedure. Considering the ongoing COVID-19 global pandemic, it is essential to devise methods to minimize aerosolization and hence ensure safety of the healthcare workers during the operative procedure. METHODS: Two disposable surgical drapes are used to create a closed pocket prior to commencement of mastoid bone-drilling. This limits aerosolization of bone-dust in the external operating theatre environment. CONCLUSION: Two-drape closed pocket technique is an easy, cost-effective and safe method to limit aerosolization of tissue particles during mastoidectomy.

Bond strength of soft liners to denture base resins and the influence of different surface treatments and thermocycling: A systematic review.

STATEMENT OF PROBLEM: Occasional debonding between soft liners and denture base resin is common and limits the longevity of a relined prosthesis. PURPOSE: The purpose of this systematic review was to compare the bond strength of commercially available soft liners with that of polymethyl methacrylate (PMMA) and urethane dimethacrylate (UDMA) denture base resins after different surface treatments and thermocycling. MATERIAL AND METHODS: Searches were performed by 2 independent reviewers in the MEDLINE/PubMed and Cochrane Library databases from January 1990 to December 2018 to identify published journal articles related to this subject. Subsequently, a hand search was also carried out for all the articles mentioned in the references of the identified full articles. RESULTS: A total of 61 articles were initially identified through database searches by the 2 reviewers. Twenty-four of the 61 articles met the inclusion criteria for qualitative analysis. Four of 6 articles showed that laser pretreatment of denture base resins increased their bonding to soft liners. Seven of 8 articles concluded that airborne-particle abrasion caused deterioration of the bonding between the liner and denture base resin. Four of 6 studies showed that acid etching, silica coating, primer or monomer application, and immersion in acetone or isobutyl methacrylate (iBMA) resulted in improved bond strengths between the liner and resin. One study reported that oxygen plasma treatment also resulted in improved bond strengths. Seven of 8 articles concluded that thermocycling resulted in decreased bond strengths. CONCLUSIONS: Laser treatment, oxygen plasma pretreatment, primer or monomer application, and immersion in acetone or iBMA resulted in improved bonding of the denture base resin to soft liners. However, airborne-particle abrasion and thermocycling resulted in deterioration of the bond.

Cep78 controls centrosome homeostasis by inhibiting EDD-DYRK2-DDB1VprBP.

The centrosome plays a critical role in various cellular processes including cell division and cilia formation, and deregulation of centrosome homeostasis is a hallmark feature of many human diseases. Here, we show that centrosomal protein of 78 kDa (Cep78) localizes to mature centrioles and directly interacts with viral protein R binding protein (VprBP). Although VprBP is a component of two distinct E3 ubiquitin ligases, EDD-DYRK2-DDB1VprBP and CRL4VprBP, Cep78 binds specifically to EDD-DYRK2-DDB1VprBP and inhibits its activity. A pool of EDD-DYRK2-DDB1VprBP is active at the centrosome and mediates ubiquitination of CP110, a novel centrosomal substrate. Deregulation of Cep78 or EDD-DYRK2-DDB1VprBP perturbs CP110 ubiquitination and protein stability, thereby affecting centriole length and cilia assembly. Mechanistically, ubiquitination of CP110 entails its phosphorylation by DYRK2 and binding to VprBP Cep78 specifically impedes the transfer of ubiquitin from EDD to CP110 without affecting CP110 phosphorylation and binding to VprBP Thus, we identify Cep78 as a new player that regulates centrosome homeostasis by inhibiting the final step of the enzymatic reaction catalyzed by EDD-DYRK2-DDB1VprBP.

Copper oxide nanoparticles as an effective anti-biofilm agent against a copper tolerant marine bacterium, Staphylococcus lentus.

Biofilm formation on antifouling coatings is a serious concern in seawater cooling systems and the maritime industry. A prolific biofilm forming strain (Staphylococcus lentus), possessing high tolerance (>1,000 µg ml-1) to dissolved copper ions (Cu++) was isolated from titanium coupons exposed in the coastal waters of Kalpakkam, east coast of India. S. lentus formed increased biofilm (p < 0.05) at 100 µg ml-1 of Cu++ ions, when compared with the untreated control. To combat biofilm formation of this strain, the efficacy of copper oxide nanoparticles synthesized from copper nitrate by varying the concentrations of hexamine and cetyl trimethyl ammonium bromide (CTAB), was investigated. Complete (100%) inhibition of biofilm formation was observed with plain CuO NP (0.5 M hexamine, uncapped) at 1,000 µg ml-1. Capping with CTAB, influenced the morphology and the purity of the synthesized CuO NPs but did not alter their surface charge. Capping reduced metal ion release from CuO NPs and their antibacterial and anti-biofilm property against S. lentus. Overall, uncapped CuO NPs were effective in controlling biofilm formation of S. lentus. Concurrent release of copper ions and contact mediated physical damage by CuO NPs offer a promising approach to tackle metal tolerant biofilm bacteria.

Comparative evaluation of condylar inclination in dentulous subjects as determined by two radiographic methods: Orthopantomograph and cone-beam computed tomography - An in vivo study.

AIM: The aim of the study was to compare two radiographic techniques, orthopantomograph (OPG), and cone-beam computed tomography (CBCT) in determining the sagittal condylar guidance (SCG) and to find out if CBCT can serve as an alternative aid to program semi-adjustable and fully adjustable articulators. MATERIALS AND METHODS: Following the inclusion and exclusion criteria, 40 individuals (20 males and 20 females) aged between 20 and 40 years were selected. An OPG and a CBCT radiograph were obtained for each individual. Using appropriate software, the SCG was measured for both the sides, for both the radiographic methods. The values for each individual were obtained by two investigators for both the methods using the respective software and the average value was taken. After performing the Shapiro-Wilk test, paired t-test was used to compare the mean difference pairwise (for both right and left side) while t-test was used to compare the mean difference between two groups. RESULTS: Results showed that the right and left SCG values obtained from both, OPG and CBCT methods were comparable and there were no significant differences. Statistically significant difference was not found between the left and ride side condylar inclination values for both the sex obtained from both the methods. With increasing age, condylar inclination values obtained from both the radiographic methods tend to decrease. The values for SCG obtained from both the methods (CBCT and OPG) are thus comparable and correlated. CONCLUSION: The values for SCG obtained from both the methods (CBCT and OPG) are comparable and correlated. Thus, CBCT being a better radiographic technique can be used for obtaining the condylar inclination for programming the semi-adjustable and fully adjustable dental articulators.

Flasking technique with alum crystals for fabricating definitive hollow bulb obturators.

Different techniques have been described for fabricating obturators for patients with maxillary defects. The hollow bulb obturator has emerged as the treatment of choice in most patients owing to its light weight, cleanliness, and ease of fabrication. This article presents a simplified flasking technique for fabricating a definitive, closed, hollow bulb obturator by using a potassium alum crystal.

Rhodium-Catalyzed sp2 C-H Acetoxylation of N-Aryl Azaindoles/N-Heteroaryl Indolines.

A silver- and copper-free rhodium-catalyzed C-H acetoxylation reaction of azaindoles has been achieved at near ambient temperature employing PIDA as a nonmetallic acetoxy source. The method is highly selective, efficient, and scalable and requires acetic anhydride as the sole additive. The scope of the reaction has been successfully tested with a wide array of medicinally important heterocyclic scaffolds with diverse functional group tolerance. A series of kinetic experiments was conducted to gain detailed insight into the reaction mechanism. The methodology developed could be successfully expanded for C7-acetoxylation of indoline derivatives using pyrimidine as a detachable directing group for the synthesis of 7-hydroxyindole.

Safety profiling of pioglitazone and telmisartan combination by sub-chronic toxicity study in rat.

It has been reported that the major cause of mortality in diabetes is cardiovascular diseases and contribution of hypertension is significant in this context. Pioglitazone, a thiazolidinedione class of therapeutic agent is used to treat type 2 diabetes mellitus. Telmisartan, an angiotensin receptor blocker antihypertensive has been reported to have beneficial effect if co-administered with pioglitazone for the management of diabetes complications. The present research work aims to evaluate the safety/toxicity profile of this combination in rat model. The investigation was carried out after co-administering the drugs to the rats for 28 days at three dose levels of 50, 100 and 150 mg/kg covering low to high dose ranges. Various hematological and biochemical parameters were studied in addition to the histopathology of the major organs in order to evaluate the toxicity profile of the combination. Absence of mortality and histopathological changes as well as unaltered hematological and biochemical parameters was observed. This preliminary investigation concludes that the combination of pioglitazone and telmisartan can primarily be stated as safe in animals, even at the dose level which is several folds higher than the intended human dose. Thus, this combination can be explored in future to develop a rational therapy regimen to treat hypertensive diabetic patients.

Understanding collaboration in a multi-national research capacity-building partnership: a qualitative study.

BACKGROUND: Research capacity building and its impact on policy and international research partnership is increasingly seen as important. High income and low- and middle-income countries frequently engage in research collaborations. These can have a positive impact on research capacity building, provided such partnerships are long-term collaborations with a unified aim, but they can also have challenges. What are these challenges, which often result in a short term/ non viable collaboration? Does such collaboration results in capacity building? What are the requirements to make any collaboration sustainable? This study aimed to answer these and other research questions through examining an international collaboration in one multi-country research capacity building project ARCADE RSDH (Asian Regional Capacity Development for Research on Social Determinants of Health). METHOD: A qualitative study was conducted that focused on the reasons for the collaboration, collaboration patterns involved, processes of exchanging information, barriers faced and perceived growth in research capacity. In-depth interviews were conducted with the principal investigators (n = 12), research assistants (n = 2) and a scientific coordinator (n = 1) of the collaborating institutes. Data were analysed using thematic framework analysis. RESULTS: The initial contact between institutes was through previous collaborations. The collaboration was affected by the organisational structure of the partner institutes, political influences and the collaboration design. Communication was usually conducted online, which was affected by differences in time and language and inefficient infrastructure. Limited funding resulted in restricted engagement by some partners. CONCLUSION: This study explored work in a large, North-South collaboration project focusing on building research capacity in partner institutes. The project helped strengthen research capacity, though differences in organization types, existing research capacity, culture, time, and language acted as obstacles to the success of the project. Managing these differences requires preplanned strategies to develop functional communication channels among the partners, maintaining transparency, and sharing the rewards and benefits at all stages of collaboration.

Photoluminescence of oxygen vacancies and hydroxyl group surface functionalized SnO2 nanoparticles.

We report, for the first time, the luminescence property of the hydroxyl group surface functionalized quantum dots (QDs) and nanoparticles (NPs) of SnO2 using low energy excitations of 2.54 eV (488 nm) and 2.42 eV (514.5 nm). This luminescence is in addition to generally observed luminescence from 'O' defects. The as-prepared SnO2 QDs are annealed at different temperatures under ambient conditions to create NPs with varying sizes. Subsequently, the average size of the NPs is calculated from the acoustic vibrations observed at low frequencies in the Raman spectra and by the transmission electron microscopy measurements. Detailed photoluminescence studies with 3.815 eV (325 nm) excitation reveal the nature of in-plane and bridging 'O' vacancies as well as adsorption and desorption occurring at different annealing temperatures. X-ray photoelectron spectroscopy studies also support this observation. The defect level related to the surface -OH functional groups shows a broad luminescence peak at around 1.96 eV in SnO2 NPs which is elaborated using temperature dependent studies.