Exploiting the co-crystal ligands shape, features and structure-based approaches for identification of SARS-CoV-2 Mpro inhibitors.

SARS-CoV-2 enters the host cell through the ACE2 receptor and replicates its genome using an RNA-Dependent RNA Polymerase (RDRP). The functional RDRP is released from pro-protein pp1ab by the proteolytic activity of Main protease (Mpro) which is encoded within the viral genome. Due to its vital role in proteolysis of viral polyprotein chains, it has become an attractive potential drug target. We employed a hierarchical virtual screening approach to identify small synthetic protease inhibitors. Statistically optimized molecular shape and color-based features (various functional groups) from co-crystal ligands were used to screen different databases through various scoring schemes. Then, the electrostatic complementarity of screened compounds was matched with the most active molecule to further reduce the hit molecules' size. Finally, five hundred eighty-seven molecules were docked in Mpro catalytic binding site, out of which 29 common best hits were selected based on Glide and FRED scores. Five best-fitting compounds in complex with Mpro were subjected to MD simulations to analyze their structural stability and binding affinities with Mpro using MM/GB(PB)SA models. Modeling results suggest that identified hits can act as the lead compounds for designing better active Mpro inhibitors to enhance the chemical space to combat COVID-19.Communicated by Ramaswamy H. Sarma.

Investigations of p-tolyloxy-1,3,4-oxadiazole propionamides as soybean 15-lipoxygenase inhibitors in comforting with in vitro and in silico studies.

Inflammatory disorders are the prime contributor to public health issue and the development of more effective and safer anti-inflammatory drugs in addition to other therapeutic alternatives to treat inflammatory illnesses, particularly chronic inflammatory diseases, is one of the foremost current issues. In this regard, our present work is concerned with the synthesis of a new series of N-alkyl/aralkyl/aryl derivatives (7a-o) of 5-((p-tolyloxymethyl)-4H-1,3,4-oxadiazole-2-ylthio)propionamide which was instigated by the successive conversions of p-tolyloxyacetic acid into ester, hydrazide and 5-(p-tolyloxymethyl)-4H-1,3,4-oxadiazole-2-thiol. The planned compounds (7a-o) were attained by the reaction of 5-(p-tolyloxymethyl)-4H-1,3,4-oxadiazole-2-thiol with variety of N-alkyl/aralkyl/aryl electrophiles in potassium hydroxide and were characterized by FTIR, 1H-, 13C-NMR spectroscopy, EI-MS and HR-EI-MS spectrometry and probed for their inhibiting potential against soybean 15-lipoxygenase (15-LOX) enzyme. The compounds 7a, 7n, 7 g, 7e, 7h, 7i, 7j and 7b promulgated the potent inhibiting potential with IC50 values 9.43 ± 0.45, 16.75 ± 0.49, 19.45 ± 0.37, 21.32 ± 0.46, 22.64 ± 0.56, 23.53 ± 0.62, 24.32 ± 0.45 and 29.15 ± 0.57 µM, respectively, while excellent to good inhibitory activities were shown by 7o, 7 m, 7k, 7f, 7c, 7 l and 7d with IC50 values in the range 30.29 ± 0.56 to 52.54 ± 0.64 µM. Compounds 7i-o maintained 91.12 ± 1.5 to 98.23 ± 1.2% blood mononuclear cells (MNCs) viability at 0.25 mM by MTT assay whilst compounds 7d-h observed 46.51 ± 1.3 to 57.12 ± 1.4% viability where as the most toxic compounds were 7b (12.51 ± 1.4%), 7a (28.12 ± 1.5%) and 7c (38.23 ± 1.5%) as compared with controls. Pharmacokinetic profiles predicted good oral bioavailability and drug-likeness properties of molecules as per rule of five. Molecular docking studies displayed hydrogen bonding between the compounds and the enzyme with Arg378 which was common in 7n, 7 g, 7h and baicalein. In 7a and quercetin, hydrogen bonding was established through Asn375; Tyr512 and Val589 were also involved in bonding with other analogues. RMSD (root mean square deviation) values exhibited good inhibitory profiles in the order quercetin (0.73 Å)<7 g (0.98 Å)

Genome Editing Technology: A New Frontier for the Treatment and Prevention of Cardiovascular Diseases.

Over the past two decades, genome-editing technique has proven to be a robust editing method that revolutionizes the field of biomedicine. At the genetic level, it can be efficiently utilized to generate various disease-resistance models to elucidate the mechanism of human diseases. It also develops an outstanding tool and enables the generation of genetically modified organisms for the treatment and prevention of various diseases. The versatile and novel CRISPR/Cas9 system mitigates the challenges of various GETs such as ZFNs, and TALENs. For this reason, it has become a ground-breaking technology potentially employed to manipulate the desired gene of interest. Interestingly, this system has been broadly utilized due to its tremendous applications for treating and preventing tumors and various rare disorders; however, its applications for treating CVDs remain in infancy. More recently, two newly developed GETs, such as base editing and prime editing, have further broadened the accuracy range to treat CVDs under consideration. Furthermore, recently emerged CRISPR tools have been potentially applied in vivo and in vitro to treat CVDs. To the best of our knowledge, we strongly enlightened the applications of the CRISPR/Cas9 system that opened a new window in the field of cardiovascular research and, in detail, discussed the challenges and limitations of CVDs.

Sensitive or tolerant functional microorganisms under cadmium stress: suggesting potential specific interaction network characteristics in the rhizosphere system of karst potato.

The heavy metal cadmium (Cd) pollution in Chinese karst soils threatens food security, and microorganisms play an important role in regulating the migration and transformation of Cd in the soil-plant system. Nevertheless, the interaction characteristics between key microbial communities and environmental factors in response to Cd stress in specific crop environmental systems need to be explored. In this study, the soil (ferralsols)-microbe-crop (potato) system was taken as the object to explore the potato rhizosphere microbiome, using toxicology and molecular biology approaches, to explore the potato rhizosphere soil properties, microbial stress characteristics, and important microbial taxa under Cd stress. We hypothesized that different members of fungal and bacterial microbiome would regulate the resilience of potato rhizosphere and plants to Cd stress in the soil environment. Meanwhile, individual taxa will have different roles in the contaminated rhizosphere ecosystem. We found that soil pH was the main environmental factor affecting fungal community structure; urea-decomposing and nitrate-reducing functional bacteria as well as endosymbiotic and saprophytic functional fungi gradually decreased. In particular, Basidiomycota may play a key role in preventing the migration of Cd from the soil to plants (potato). These findings provide important candidates for screening the cascade of Cd inhibition (detoxification/regulation) from soil to microorganisms to plants. Our work provides an important foundation and research insights for the application of microbial remediation technology in the karst cadmium-contaminated farmland.

SeDeM expert system with I-optimal mixture design for oral multiparticulate drug delivery: An encapsulated floating minitablets of loxoprofen Na and its in silico physiologically based pharmacokinetic modeling.

Introduction: A SeDeM expert tool-driven I-optimal mixture design has been used to develop a directly compressible multiparticulate based extended release minitablets for gastro-retentive drug delivery systems using loxoprofen sodium as a model drug. Methods: Powder blends were subjected to stress drug-excipient compatibility studies using FTIR, thermogravimetric analysis, and DSC. SeDeM diagram expert tool was utilized to assess the suitability of the drug and excipients for direct compression. The formulations were designed using an I-optimal mixture design with proportions of methocel K100M, ethocel 10P and NaHCO3 as variables. Powder was compressed into minitablets and encapsulated. After physicochemical evaluation lag-time, floating time, and drug release were studied. Heckel analysis for yield pressure and accelerated stability studies were performed as per ICH guidelines. The in silico PBPK Advanced Compartmental and Transit model of GastroPlus™ was used for predicting in vivo pharmacokinetic parameters. Results: Drug release follows first-order kinetics with fickian diffusion as the main mechanism for most of the formulations; however, a few formulations followed anomalous transport as the mechanism of drug release. The in-silico-based pharmacokinetic revealed relative bioavailability of 97.0%. Discussion: SeDeM expert system effectively used in QbD based development of encapsulated multiparticulates for once daily administration of loxoprofen sodium having predictable in-vivo bioavailability.

Contamination Assessment and Potential Human Health Risks of Heavy Metals in Urban Soils from Grand Forks, North Dakota, USA.

Heavy metal (HM) pollution of soil is an increasingly serious problem worldwide. The current study assessed the metal levels and ecological and human health risk associated with HMs in Grand Forks urban soils. A total 40 composite surface soil samples were investigated for Mn, Fe, Co, Ni, Cu, Zn, As, Pb, Hg, Cr, Cd and Tl using microwave-assisted HNO3-HCl acid digestion and inductively coupled plasma mass spectrometry (ICP-MS) analysis. The enrichment factor (EF), contamination factor (CF), geoaccumulation index (Igeo), ecological risk and potential ecological risk index were used for ecological risk assessment. The park soils revealed the following decreasing trend for metal levels: Fe > Mn > Zn > Cr > Ni > Cu > Pb > As > Co > Cd > Tl > Hg. Based on mean levels, all the studied HMs except As and Cr were lower than guideline limits set by international agencies. Principal component analysis (PCA) indicated that Mn, Fe, Co, Ni, Cu, Zn, As, Cd, Pb, Cr and Tl may originate from natural sources, while Hg, Pb, As and Cd may come from anthropogenic/mixed sources. The Igeo results showed that the soil was moderately polluted by As and Cd and, based on EF results, As and Cd exhibited significant enrichment. The contamination factor analysis revealed that Zn and Pb showed moderate contamination, Hg exhibited low to moderate contamination and As and Cd showed high contamination in the soil. Comparatively higher risk was noted for children over adults and, overall, As was the major contributor (>50%), followed by Cr (>13%), in the non-carcinogenic risk assessment. Carcinogenic risk assessment revealed that As and Cr pose significant risks to the populations associated with this urban soil. Lastly, this study showed that the soil was moderately contaminated by As, Cd, Pb and Hg and should be regularly monitored for metal contamination.

Remote Monitoring in Heart Failure patients: A Systemic Review and Meta-analysis.

Heart failure (HF) approximately affects about 1%-2% of the adult population in developed countries and is a leading cause of morbidity and mortality worldwide. Inadequate HF management occurs because of poor adherence to prescribed medications. This meta-analysis compares and contrasts standard care with remote medication monitoring in HF patients. Six randomized control trials were selected using the PubMed database from inception until October 25, 2022, incorporating a total of 2390 patients with HF, out of which 1260 were subjected to remote monitoring while the remaining were in the control group. An odds ratio (OR) with a confidence interval (CI) of 95% was calculated. Remote monitoring in HF patients did not significantly reduce the risks of Cardiovascular (CV) hospitalization <6 months (RR = 0.32, P = 0.27), emergency department (ED) visits (RR = 0.95, P = 0.56) and all-cause mortality (RR = 1.08, P = 0.36). However, a significant reduction in CV hospitalization >6 months was associated with remote monitoring (RR = 0.83, P = 0.002). The meta-analysis revealed that remote monitoring does not significantly reduce the risks of CV hospitalizations, ED visits, or mortality in patients with HF. Therefore, standard care methods must continue to be utilized in HF management.

Efficacy of priming wheat (Triticum aestivum) seeds with a benzothiazine derivative to improve drought stress tolerance.

We evaluated the effects of different concentrations (0.05 and 0.15mM) of a benzothiazine (BTh) derivative on wheat (Triticum aestivum L.) in normal (100% field water capacity, FWC) and drought (60% FWC) conditions. Various morphological and physiological characteristics, and the uptake of osmo-protectants and nutrients were measured under the two FWC conditions. Results show that the drought conditions significantly reduced plant growth, affected plant composition, reduced the concentrations of photosynthetic pigments and affected gaseous exchange attributes, stomatal behaviour, and uptake fluxes of essential nutrients, while increasing the contents of different osmo-protectants and enzymatic and non-enzymatic antioxidants to decrease the production of reactive oxygen species (ROS) within the cells/tissues. However, seed priming with BTh reduced water stress conditions by increasing plant growth and biomass, photosynthetic pigments, stomatal behaviour, different gaseous exchange attributes, and uptake fluxes of essential nutrients compared with unprimed plants. In addition, the plant has a strong antioxidant defense system, which further increased its activities under BTh derivative treatments, to scavenge ROS production and maintain cell turgor under water stress conditions. In conclusion, drought stress-induced oxidative stress and altered the growth of T. aestivum, whereas seed priming increased plant growth and antioxidant production by improving the plant tolerance to drought. We suggest that seed priming with a BTh derivative as an effective priming technique in T. aestivum for reducing drought stress tends to benefit a grower in terms of better growth to fulfil the market demand for food cereals.

Molecular evidence of Ehrlichia canis, associated risk factors and hematobiochemical analysis in client owned and shelter cats of Pakistan.

Ehrlichiosis is an infectious disease caused by Ehrlichia canis (E. canis) genus and arthropod vectors. It is considered endemic in many parts of the world among dogs. But due to lack of research on cats, there isn't enough information available. The limited reports available on feline Ehrlichiosis relied on the detection of morulae in leukocytes. The current study was designed to detect the molecular prevalence of E. canis in cats along with associated risk factors and hematological analysis. A total of 384 blood samples from cats were collected from various veterinary hospitals and shelter homes and tested by microscopy and Polymerase Chain Reaction (PCR) to identify E. canis. The prevalence of E. canis has been reported at 5/384 (1.30%) and (14/384) 3.65% in cats through microscopy and PCR respectively. DNA sequences revealed significant resemblance with each other and variable resemblance with other Ehrlichia spp. sequences of different species from various countries already deposited on NCBI. Moreover, hematobiochemical and risk factor analysis were also carried out revealing significant results. This study reports first molecular detection of E. canis in client-owned and sheltered cats located in District Lahore, Punjab, Pakistan. Further studies should be conducted to identify its occurrence in the feline population of Pakistan so that control and prevention strategies must be planned accordingly. Due to the zoonotic impact of this pathogen and in perspective of one health, endemic regions of the disease should be identified and possible control measures should be implemented in these regions to minimize the spread of disease to non-endemic regions of the world and from animals to humans.

Sooty Tern Optimization Algorithm-Based Deep Learning Model for Diagnosing NSCLC Tumours.

Lung cancer is one of the most common causes of cancer deaths in the modern world. Screening of lung nodules is essential for early recognition to facilitate treatment that improves the rate of patient rehabilitation. An increase in accuracy during lung cancer detection is vital for sustaining the rate of patient persistence, even though several research works have been conducted in this research domain. Moreover, the classical system fails to segment cancer cells of different sizes accurately and with excellent reliability. This paper proposes a sooty tern optimization algorithm-based deep learning (DL) model for diagnosing non-small cell lung cancer (NSCLC) tumours with increased accuracy. We discuss various algorithms for diagnosing models that adopt the Otsu segmentation method to perfectly isolate the lung nodules. Then, the sooty tern optimization algorithm (SHOA) is adopted for partitioning the cancer nodules by defining the best characteristics, which aids in improving diagnostic accuracy. It further utilizes a local binary pattern (LBP) for determining appropriate feature retrieval from the lung nodules. In addition, it adopts CNN and GRU-based classifiers for identifying whether the lung nodules are malignant or non-malignant depending on the features retrieved during the diagnosing process. The experimental results of this SHOA-optimized DNN model achieved an accuracy of 98.32%, better than the baseline schemes used for comparison.

Quality Analysis of Canola and Mustard Oil Using Fluorescence Spectroscopy.

The potential of Fluorescence spectroscopy has been utilized for the quality analysis of canola and mustard oil along with the effect of heating on their molecular composition has been investigated. Laser diode at 405 nm has been employed directly to oil surface to excite both oil type samples and their emission spectra has been recorded by an in-house developed Fluorosensor. The emission spectra of both oil types unveiled that they contain carotenoids, isomers of vitamin E and chlorophylls that exhibit their fluorescence at 525 and 675/720 nm, and these can be used as markers for their quality assurance. Fluorescence spectroscopy is a fast, reliable and non-destructive analytical technique for the quality assessment of both oil types. Moreover, the effect of temperature on their molecular composition has been investigated by heating them at 110, 120, 130, 140, 150, 170, 180 and 200 °C, each sample for 30 min which was done because both oils are used for cooking and frying. On heating, the deterioration of carotenoids and isomers of vitamin E in both oil types occurred with an increase in the oxidised products. However, it was found that up to 150 °C, both oil types can be used safely for cooking/frying purpose where they do not lose much of their valuable ingredients and up to 180 °C for deep frying, both oils can be used with less deterioration and after that both deteriorated much due to rapid increase of the oxidized products. The portable Fluorosensor, therefore, proved as an excellent device for quality screening of edible oils based on carotenoids and vitamin E.

Thermal Effects on the Quality Parameters of Extra Virgin Olive Oil Using Fluorescence Spectroscopy.

Extra virgin olive oil is one of the superlative due to its health benefits. In this work, the Fluorescence spectra of extra virgin olive oil (EVOO) from different olive growing regions of Pakistan and Al-Jouf region from the Kingdom of Saudi Arabia (KSA) were obtained. The emission bands depicted relative intensity variations in all non-heated and heated EVOO samples. Prominent emission bands at 385, 400, 435 and 470 nm represent oxidized products of fatty acids, bands at 520 and 673 nm has been assigned to beta carotene and chlorophyll isomers respectively. All EVOO samples collected from Al-Jouf region, KSA and from Pakistan (Loralai Baluchistan, Barani Agricultural Research Institute, Chakwal and Morgha Biodiversity Park, Rawalpindi) regions showed thermal stability. Other EVOO samples from Chaman Baluchistan and one sample from wild specie (Baluchistan) bought directly from farmers showed denatured spectra even without heating. Chemical characteristics of all EVOO samples changed significantly at 200 °C. Relatively, EVOO samples from Al-Jouf showed more thermal stability which might be due to geographical distribution, environmental effects, genetic background and processing or storage conditions. These results demonstrated fluorescence spectroscopy as a quick, cost-effective and reliable approach to assess the quality and thermal stability of EVOO. These characteristics of fluorescence spectroscopy may lead to the development of portable device for the onsite monitoring of EVOO.

Analysis of gaze patterns during facade inspection to understand inspector sense-making processes.

This work seeks to capture how an expert interacts with a structure during a facade inspection so that more detailed and situationally-aware inspections can be done with autonomous robots in the future. Eye tracking maps where an inspector is looking during a structural inspection, and it recognizes implicit human attention. Experiments were performed on a facade during a damage assessment to analyze key, visually-based features that are important for understanding human-infrastructure interaction during the process. For data collection and analysis, experiments were conducted to assess an inspector's behavioral changes while assessing a real structure. These eye tracking features provided the basis for the inspector's intent prediction and were used to understand how humans interact with the structure during the inspection processes. This method will facilitate information-sharing and decision-making during the inspection processes for collaborative human-robot teams; thus, it will enable unmanned aerial vehicle (UAV) for future building inspection through artificial intelligence support.

Genetic Biodiversity and Posttranslational Modifications of Protease Serine Endopeptidase in Different Strains of Sordaria fimicola.

Genetic variations (mutation, crossing over, and recombination) act as a source for the gradual alternation in phenotype along a geographic transect where the environment changes. Posttranslational modifications (PTMs) predicted modifications successfully in different and the same species of living organisms. Protein diversity of living organisms is predicted by PTMs. Environmental stresses change nucleotides to produce alternations in protein structures, and these alternations have been examined through bioinformatics tools. The goal of the current study is to search the diversity of genes and posttranslational modifications of protease serine endopeptidase in various strains of Sordaria fimicola. The S. fimicola's genomic DNA was utilized to magnify the protease serine endopeptidase (SP2) gene; the size of the product was 700 and 1400 base pairs. Neurospora crassa was taken as the reference strain for studying the multiple sequence alignment of the nucleotide sequence. Six polymorphic sites of six strains of S. fimicola with respect to N. crassa were under observation. Different bioinformatics tools, i.e., NetPhos 3.1, NetNES 1.1 Server, YinOYang1.2, and Mod Pred, to search phosphorylation sites, acetylation, nuclear export signals, O-glycosylation, and methylation, respectively, were used to predict PTMs. The findings of the current study were 35 phosphorylation sites on the residues of serine for protease SP2 in SFS and NFS strains of S. fimicola and N. crassa. The current study supported us to get the reality of genes involved in protease production in experimental fungi. Our study examined the genetic biodiversity in six strains of S. fimicola which were caused by stressful environments, and these variations are a strong reason for evolution. In this manuscript, we predicted posttranslational modifications of protease serine endopeptidase in S. fimicola obtained from different sites, for the first time, to see the effect of environmental stress on nucleotides, amino acids, and proteases and to study PTMs by using various bioinformatics tools. This research confirmed the genetic biodiversity and PTMs in six strains of S. fimicola, and the designed primers also provided strong evidence for the presence of protease serine endopeptidase in each strain of S. fimicola.

Assessment of cumulative microbial respiration and their ameliorative role in sustaining maize growth under salt stress.

Cumulative microbial respiration reflects microbial activities and their potential to support plant growth, where salt tolerant rhizobacteria can optimize their respiration, and ensure plant survival under salt stress. We evaluated cumulative microbial respiration of different salt tolerant rhizobacterial strains at different salinity levels, and checked their ability to sustain plant growth under natural saline conditions by using maize as test crop. Our results revealed that at the highest EC level (10 dS m-1), strain 'SUA-14' performed significantly better, and exhibited the greatest cumulative respiration (4.2 fold) followed by SHM-13 (3.8 fold), as compared to un-inoculated control. Moreover, results of the field trial indicated a similar trend, where significant improvements in shoot fresh weight (59%), root fresh weight (80%), shoot dry weight (56%), root dry weight (1.4 fold), leaf area (1.9 fold), straw yield (41%), cob diameter (33%), SPAD value (84%), yield (99%), relative water contents (91%), flavonoid (55%), 1000 grain weight (∼100%), soluble sugars (41%) and soluble proteins (45%) were observed due to inoculation of strain 'SUA-14' as compared to un-inoculated control. Similarly, substantial decline in leaf Na+ (34%), Na+/K+ ratio (69%), electrolyte leakage (8%), catalase (54%), peroxidase (73%), and H2O2 (50%) activities were observed after inoculation of 'SUA-14' with a concomitant increment in the leaf K+ contents (70%) under salinity stress than un-inoculated control. Hence, among all the tested rhizobacterial isolates, 'SUA-14' served as the most efficient strain in alleviating the detrimental impacts of salinity on maize growth and yield. The 16S rRNA sequencing identified it as Acinetobacter johnsonii.

Genome analysis of novel Apilactobacillus sp. isolate from butterfly (Pieris canidia) gut reveals occurrence of unique glucanogenic traits and probiotic potential.

This study was conducted with a perception that fructose-rich niches may inhabit novel species of lactic acid bacteria that are gaining importance as probiotics and for the production of exopolysaccharides that have applications in food and pharmaceuticals. Recently, some Lactobacillus species have been reclassified as fructophilic lactic acid bacteria due to their preference for fructose over glucose as a carbon source. These bacteria are likely to be found in fructose rich niches such as flower nectar and insects that feed on it. We explored the butterfly gut and acquired a new isolate, designated as F1, of fructophilic lactic acid bacteria, which produces a glucan-type exopolysaccharide. Whole genome sequencing and in silico analysis revealed that F1 has significantly lower average nucleotide identity and DNA-DNA hybridization values as compared to its closest Apilactobacillus neighbors in phylogenetic analysis. Therefore, we declare the isolate F1 as a novel Apilactobacillus species with the proposed name of Apilactobacillus iqraium F1. Genome mining further revealed that F1 harbors genes for exopolysaccharide synthesis and health-promoting attributes. To this end, F1 is the only Apilactobacillus species harboring three diverse α-glucan-synthesis genes that cluster with different types of dextransucrases in the dendrogram. Moreover, many nutritional marker genes, as well as genes for epithelial cell adhesion and antimicrobial synthesis, were also detected suggesting the probiotic attributes of F1. Overall analysis suggests A. iqraium sp. F1 be a potential candidate for various health beneficial and pharmaceutical applications.

In vivo assessment of artefacts in MRI images caused by conventional twistflex and various fixed orthodontic CAD/CAM retainers.

PURPOSE: To assess magnetic resonance imaging (MRI) artefacts caused by different computer-aided design/computer-aided manufacturing (CAD/CAM) retainers in comparison with conventional hand bent stainless steel twistflex retainers in vivo. MATERIALS AND METHODS: MRI scans (3 Tesla) were performed on a male volunteer with different CAD/CAM retainers (cobalt-chromium, CoCr; nickel-titanium, NiTi; grade 5 titanium, Ti5) and twistflex retainers inserted. A total of 126 landmarks inside and outside the retainer area (RA; from canine to canine) were evaluated by two blinded radiologists using an established five-point visibility scoring (1: excellent, 2: good, 3: moderate, 4: poor, 5: not visible). Friedman and two-tailed Wilcoxon tests were used for statistical analysis (significance level: p < 0.05). RESULTS: Twistflex retainers had the strongest impact on the visibility of all landmarks inside (4.0 ± 1.5) and outside the RA (1.7 ± 1.2). In contrast, artefacts caused by CAD/CAM retainers were limited to the dental area inside the RA (CoCr: 2.2 ± 1.2) or did not impair MRI-based diagnostics in a clinically relevant way (NiTi: 1.0 ± 0.1; Ti5: 1.4 ± 0.6). CONCLUSION: The present study on a single test person demonstrates that conventional stainless steel twistflex retainers can severely impair the diagnostic value in head/neck and dental MRI. By contrast, CoCr CAD/CAM retainers can cause artefacts which only slightly impair dental MRI but not head/neck MRI, whereas NiTi and Ti5 CAD/CAM might be fully compatible with both head/neck and dental MRI.

Clinical and Biochemical Characteristics of Male Idiopathic Hypogonadotropic Hypogonadism Patients: A Retrospective Cross Sectional Study.

BACKGROUND: Idiopathic hypogonadotropic hypogonadism (IHH) is a medical condition where there is a deficiency or insensitivity of gonadotropin-releasing hormone (GnRH) without a known cause. Not only are the sexual characteristics of a person affected by this condition but also are the psychological and physical development, thus necessitating its early recognition and treatment. This research was carried out to identify the laboratory parameters and to present symptoms of the patients with complaints of IHH. MATERIALS AND METHODS: This retrospective, center, single-center, cross-sectional study was carried out in Aga Khan University from December 2000 until December 2020 on the patients that presented to the clinic with IHH. The patients included in the study were those that presented with hypogonadism, a low concentration of sex steroid hormone, and an abnormal gonadotropin level without any expansive pituitary or hypothalamic lesion. RESULTS: Seventy nine patients presenting with IHH were included with their mean age of 24.2 ± 7.5 years. Of these, 64 (81.0%) had genital atrophy, 50 (63.6%) showed an absence of secondary sexual characteristics, 53 (67.1%) complained of infertility, 44 (55.7%) had not shown signs of puberty, 52 (65.8%) had erectile dysfunction, 46 (58.2%) had a decrease in libido, 11(13.9%) had a previous familial history, 24 (30.3%) had gynecomastia, 9 (11.4%) had non-descended testes, and 6 (7.6%) had anosmia. These patients had serum testosterone, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels of 26.3 ± 60, 1.3 ± 2.4, and 2.7 ± 5.0 (IU/L), respectively. CONCLUSION: Thus, it can be stated that small genitalia is the most common complaint among patients with IHH, followed by infertility and lack of secondary sexual characteristics. The testosterone level in serum is also found to be low among these patients.

The Evaluation of Clinical Signs and Symptoms of Malignant Tumors Involving the Maxillary Sinus: Recommendation of an Examination Sieve and Risk Alarm Score.

This observational study was conducted to evaluate the clinical signs and symptoms of maxillary sinus tumors and to propose a clinical examination sieve and a unique risk alarm score to be used for timely patient referral and vigilance. The study consisted of 70 patients between 20 to 82 years of age from both sexes. The clinical information gained was collected from the upper dentoalveolar segment, orbit, and nasal sites. Regarding the early clinical sign and symptoms of patients, nasal obstruction was found in 67 patients (95.7%), facial swelling in 69 patients (98.6%), paresthesia in 41 patients (58.6%), and epistaxis in 50 patients (71.4%). Furthermore, in terms of the late signs and symptoms, a palpable mass in buccal sulcus was observed in 65 (92.9%) of the patients, lymphadenopathy in 24 (34.3%), paresthesia in 38 (54.3%), and diplopia in 22 (31.4%). Furthermore, general sign and symptoms like exophthalmos was present in 35 patients (50%), anosmia was observed in 37 patients (52.9%), and oroantral fistula was noted in 37 patients (55.9%). Additionally, 67 (95.7%) of the patients complained of nasal obstruction. Similarly, facial asymmetry was observed in 69 (98.6%) of the patients and double vision was observed in 24 (34.4%). Tumors of the maxillary sinus have a very insidious course of spread and uncertain clinical signs and symptoms. What makes diagnosis worse is the fact that the symptoms of these tumors are so well hidden in the sponge-like nature of the midfacial region that they are easily misinterpreted by patients. Therefore, diagnoses must be made early, dentists must be vigilant, and patients must be fully investigated at the slightest suspicion of a tumor, albeit benign.

Helical Milling of CFRP/Ti6Al4V Stacks Using Nano Fluid Based Minimum Quantity Lubrication (NF-MQL): Investigations on Process Performance and Hole Integrity.

The structural components in the aeronautical industry require CFRP/Ti6Al4V stacks to be processed together, which results in poor hole integrity due to the thermal properties of the materials and challenges related to processability. These challenges include quality variation of the machined holes because of the limitations in process properties. Therefore, a novel solution through helical milling is investigated in the study using nano fluid based minimum quantity lubrication (NF-MQL). The analysis of variance shows, for Ti6Al4V, eccentricity (PCR = 28.56%), spindle speed (Ti) (PCR = 42.84%), and tangential feed (PCR = 8.61%), and for CFRP, tangential feed (PCR = 40.16%), spindle speed (PCR = 28.75%), and eccentricity (PCR = 8.41%) are the most significant parameters for diametric error. Further on, the rise in the circularity error is observed because of prolonged tool engagement at a higher value of tangential feed. Moreover, the surface roughness of Ti was reduced with an increasing percentage of MoS2 in the lubricant. The spindle speed (37.37%) and lubricant (45.76%) have a potential influence on the processing temperature, as evident in the analysis of variance. Similarly, spindle speed Ti (61.16%), tangential feed (23.37%), and lubrication (11.32%) controlled flank wear, which is critical to tool life. Moreover, the concentration of MoS2 decreased edge wear from ~105 µm (0.5% concentration) to ~70 µm (1% concentration). Thorough analyses on process performance in terms of hole accuracy, surface roughness, processing temperature, and tool wear are carried out based on the physical science of the process for cleaner production. The NF-MQL has significantly improved process performance and hole integrity.