Comprehensive Analysis of Omicron Subvariants: EG.5 Rise, Vaccination Strategies, and Global Impact.

The emergence of new variants of the SARS-CoV-2 virus during the COVID-19 pandemic has prompted significant developments in the understanding, monitoring, and response to these strains. This comprehensive review focuses on two prominent variants of interest (VoI), XBB. 1.5 (Kraken) and XBB.1.16 ("Arcturus"), along with seven variants under observation (VuM), including EG.5. The World Health Organization (WHO) identified these variants in July 2023, highlighting EG.5's noteworthy rise in prevalence. EG.5, also known as "Eris," has exhibited an increased effective reproductive rate, prompting concerns about its contagiousness and immune evasion capabilities. With an altered spike protein in the Receptor-Binding Domain (RBD), EG.5 shares similarities with XBB.1.5 but surpasses it in prevalence, constituting 20% of COVID-19 cases in the United States by late August. EG.5's subvariant, EG.5.1, poses challenges with mutations like Q52H and F456L, contributing to its ability to bypass neutralizing antibodies. The global distribution of SARS-CoV-2 variants presents a dynamic landscape, with XBB.1.16 and other strains gaining prominence. The advent of the BA.2.86 variant further complicates the scenario, with its notable spread in regions lacking robust viral surveillance. A thorough analysis of mutations reveals the evolving nature of the Omicron variant, with distinct amino acid changes characterizing XBB.1.5, XBB.1.16, and EG.5. The WHO designates EG.5 as a "variant of interest" due to its increased contagiousness and potential immune evasion, emphasizing the need for vigilant monitoring. The risk assessment of EG.5 underscores its rapid development and growing prevalence globally. While booster vaccines targeting XBB.1.5 are in development, antiviral medications like nirmatrelvir/ritonavir (Paxlovid) continue to exhibit efficacy. In the context of the evolving variants, the FDA has granted emergency use authorization for updated COVID-19 vaccines targeting circulating strains, reflecting the adaptability of vaccination strategies to address emerging challenges. This comprehensive overview provides a nuanced understanding of the diverse Omicron subvariants, their global impact, and the ongoing efforts to combat their spread through vaccination and therapeutic interventions.

Accurate unsupervised estimation of aberrations in digital holographic microscopy for improved quantitative reconstruction.

In the context of digital in-line holographic microscopy, we describe an unsupervised methodology to estimate the aberrations of an optical microscopy system from a single hologram. The method is based on the Inverse Problems Approach reconstructions of holograms of spherical objects. The forward model is based on a Lorenz-Mie model distorted by optical aberrations described by Zernike polynomials. This methodology is thus able to characterize most varying aberrations in the field of view in order to take them into account to improve the reconstruction of any sample. We show that this approach increases the repeatability and quantitativity of the reconstructions in both simulations and experimental data. We use the Cramér-Rao lower bounds to study the accuracy of the reconstructions. Finally, we demonstrate the efficiency of this aberration calibration with image reconstructions using a phase retrieval algorithm as well as a regularized inverse problems algorithm.

The Microencapsulation of Tung Oil with a Natural Hydrocolloid Emulsifier for Extrinsic Self-Healing Applications.

In this work, tung oil was utilised as a catalyst-free self-healing agent, and an in-situ polymerization process was applied to encapsulate the tung oil core with a poly(urea-formaldehyde) (PUF) shell. The conventional poly(ethylene-alt-maleic-anhydride) (PEMA) polymer was compared to a more naturally abundant gelatin (GEL) emulsifier to compare the microcapsules' barrier, morphological, thermal, and chemical properties, and the crystalline nature of the shell material. GEL emulsifiers produced microcapsules with a higher payload (96.5%), yield (28.9%), and encapsulation efficiency (61.7%) compared to PEMA (90.8%, 28.6% and 52.6%, respectively). Optical and electron microscopy imaging indicated a more uniform morphology for the GEL samples. The thermal decomposition measurements indicated that GEL decomposed to a value 7% lower than that of PEMA, which was suggested to be attributed to the much thinner shell materials that the GEL samples produced. An innovative and novel focused ion beam (FIB) milling method was exerted on the GEL sample, confirming the storage and release of the active tung oil material upon rupturing. The samples with GEL conveyed a higher healing efficiency of 91%, compared to PEMA's 63%, and the GEL samples also conveyed higher levels of corrosion resistance.

Genomic evaluation of milk yield in a smallholder crossbred dairy production system in India.

BACKGROUND: India is the largest milk producer globally, with the largest proportion of cattle milk production coming from smallholder farms with an average herd size of less than two milking cows. These cows are mainly undefined multi-generation crosses between exotic dairy breeds and indigenous Indian cattle, with no performance or pedigree recording. Therefore, implementing genetic improvement based on genetic evaluation has not yet been possible. We present the first results from a large smallholder performance recording program in India, using single nucleotide polymorphism (SNP) genotypes to estimate genetic parameters for monthly test-day (TD) milk records and to obtain and validate genomic estimated breeding values (GEBV). RESULTS: The average TD milk yield under the high, medium, and low production environments were 9.64, 6.88, and 4.61 kg, respectively. In the high production environment, the usual profile of a lactation curve was evident, whereas it was less evident in low and medium production environments. There was a clear trend of an increasing milk yield with an increasing Holstein Friesian (HF) proportion in the high production environment, but no increase above intermediate grades in the medium and low production environments. Trends for Jersey were small but yield estimates had a higher standard error than HF. Heritability estimates for TD yield across the lactation ranged from 0.193 to 0.250, with an average of 0.230. The additive genetic correlations between TD yield at different times in lactation were high, ranging from 0.846 to 0.998. The accuracy of phenotypic validation of GEBV from the method that is believed to be the least biased was 0.420, which was very similar to the accuracy obtained from the average prediction error variance of the GEBV. CONCLUSIONS: The results indicate strong potential for genomic selection to improve milk production of smallholder crossbred cows in India. The performance of cows with different breed compositions can be determined in different Indian environments, which makes it possible to provide better advice to smallholder farmers on optimum breed composition for their environment.

Genetic diversity and effective population sizes of thirteen Indian cattle breeds.

BACKGROUND: The genetic structure of a diverse set of 15 Indian indigenous breeds and non-descript indigenous cattle sampled from eight states was examined, based on 777 k single nucleotide polymorphism (SNP) genotypes obtained on 699 animals, with sample sizes ranging from 17 to 140 animals per breed. To date, this is the largest and most detailed assessment of the genetic diversity of Indian cattle breeds. RESULTS: Admixture analyses revealed that 109 of the indigenous animals analyzed had more than 1% Bos taurus admixture of relatively recent origin. Pure indigenous animals were defined as having more than 99% Bos indicus ancestry. Assessment of the genetic diversity within and between breeds using principal component analyses, F statistics, runs of homozygosity, the genomic relationship matrix, and maximum likelihood clustering based on allele frequencies revealed a low level of genetic diversity among the indigenous breeds compared to that of Bos taurus breeds. Correlations of SNP allele frequencies between breeds indicated that the genetic variation among the Bos indicus breeds was remarkably low. In addition, the variance in allele frequencies represented less than 1.5% between the Indian indigenous breeds compared to about 40% between Bos taurus dairy breeds. Effective population sizes (Ne) increased during a period post-domestication, notably for Ongole cattle, and then declined during the last 100 generations. Although we found that most of the identified runs of homozygosity are short in the Indian indigenous breeds, indicating no recent inbreeding, the high FROH coefficients and low FIS values point towards small population sizes. Nonetheless, the Ne of the Indian indigenous breeds is currently still larger than that of Bos taurus dairy breeds. CONCLUSIONS: The changes in the estimates of effective population size are consistent with domestication from a large native population followed by consolidation into breeds with a more limited population size. The surprisingly low genetic diversity among Indian indigenous cattle breeds might be due to their large Ne since their domestication, which started to decline only 100 generations ago, compared to approximately 250 to 500 generations for Bos taurus dairy cattle.

Peroneus Longus Tendon Autograft for Anterior Cruciate Ligament Reconstruction: A Safe and Effective Alternative in Nonathletic Patients.

INTRODUCTION: Anterior cruciate ligament (ACL) is a common injury which has been conventionally managed by various graft reconstruction using bone patellar tendon bone, or quadruple hamstring autograft, to name a few. However, all these grafts are associated with many complications. Lately, peroneus longus tendon (PLT) autograft has shown promising results in this field, although there is still a dearth of data on its use. We, therefore, aimed at carrying out a study to evaluate the functional outcome and knee stability results of ACL reconstruction using PLT graft. PATIENTS AND METHODS: Patients with a completely torn ACL were included in the study. The PLT was harvested, and graft length, thickness, and harvesting time were noted intraoperatively. Knee stability and functional scores were evaluated clinically and using Lachman test (primarily) and KT-2000 arthrometer and subjectively with International Knee Documentation Committee (IKDC) score at 6, 12, and 24 months (secondary outcome) postoperatively. Ankle scores were also recorded by making use of American Orthopedic Foot and Ankle Score (AOFAS)-Hindfoot Scale. RESULTS: Forty-eight patients met the inclusion criteria. The graft harvest time was 7.4 min (5-9 min). The mean thickness of the graft on doubling was 7.9 mm (7-9 mm). Ninety-six percent of the patients were satisfied with their results of the knee surgery, and 95% of the patients had no complaints of ankle joint. The mean IKDC score postoperatively was 78.16 ± 6.23, and the mean AOFAS score was 98.4 ± 4.1. None of the patients had any neurovascular deficit. CONCLUSION: ACL reconstruction using PLT graft yields a good functional score (IKDC, KT-2000 arthrometer) even at 2-year follow-up. It is a safe and effective autograft option for ACL reconstruction.

Discovery and pharmacological evaluation of indole derivatives as potent and selective RORγt inverse agonist for multiple autoimmune conditions.

Targeting nuclear receptor RORγ is recognized to be beneficial in multiple autoimmune disorders. We disclosed new indole analogues as potent RORγ inverse agonists. RO-2 as one of the potent and orally bioavailable compounds was evaluated in various models of autoimmune disorder. It showed potent suppression of downstream markers of RORγt activity in murine and human primary cells, ex vivo PD assay and in multiple animal models of autoimmune diseases. The results indicate the potential of these indole analogues as orally bioavailable small molecule inverse agonists of RORγt, efficacious in various Th17 driven models of autoimmune disorders.

Open Reduction and Internal Fixation of Isolated Posterior Cruciate Ligament Avulsion Fractures: Clinical and Functional Outcome.

Purpose: The posterior cruciate ligament (PCL) presents commonly with avulsion fractures of its tibial attachment. An avulsion fracture of the PCL, if not surgically fixed, may lead to secondary changes in the knee joint. Various fixation techniques have been explored with use of lag screws, steel wires, absorbable screws, suture anchors and straddle nails. The purpose of this study was to evaluate the clinical and functional outcome of open reduction and internal fixation of tibial avulsion injuries of the PCL using cannulated cancellous screws. Materials and Methods: We performed open reduction and internal fixation using cannulated cancellous screws in 14 patients (mean age, 33.9 years) with isolated PCL avulsion injuries. Patients with a duration of injury more than 12 weeks were excluded. The minimum follow-up period was 12 months. Results were assessed radiologically and clinically. Final functional outcome was assessed using the Lysholm knee scoring system. Results: The average follow-up period was 13.5 months. At the final follow-up, all 14 patients achieved fracture union. The average flexion was 121.7°±9.2° with full extension achieved in all patients. Mild instability (1+) was noted in 4 patients. The Lysholm functional score was excellent in 11 patients, good in 2 patients and fair in 1 patient with an average score of 97±7.6. Conclusions: Stable early fixation for PCL avulsion injuries with early controlled mobilization provided excellent to good results. However, fixation should not be discouraged for late-presenting patients because good to fair results can be achieved in such cases.

Novel pH responsive supramolecular hydrogels of chitosan hydrochloride and polyoxometalate: In-vitro, in-vivo and preliminary safety evaluation.

In the current study, electrostatically-driven pH responsive, supramolecular hydrogels of the trilacunary Wells-Dawson-type 15-tungsto-2-phosphate polyanion (P2W15) and chitosan hydrochloride (ChCl) were prepared, using methacrylic acid as pH responsive agent using benzoyl peroxide (BPO) as initiator. The prepared hydrogels were characterized by FT-IR, SEM, XRD and thermal analyses (TGA-DSC). The swelling and pH based P2W15 release profile of the hydrogels showed maximum swellability and release at pH 7.4. Different mathematical models were applied, showing that P2W15 release followed supercase transport-II mechanism and zero-order kinetics. The cytotoxicity results showed that free and embedded P2W15 exhibited dose-dependent cytotoxicity against cancer cell lines (MCF-7; HeLa) with minimal effects on normal cells (Vero). The developed hydrogels were administered to the rabbits for determining the pharmacokinetic behavior of the polyanion. Moreover, the developed hydrogel system as well as polyanion concentration used were also checked for its oral tolerability and safety evaluation in rabbits. The histopathological studies, serum chemistry (except blood glucose level) and hematological investigations exhibited that administered hydrogel suspension at maximal tolerable dose (4000mg/kg body weight) and polyanion concentration used (20mg) were safe from in-vivo point of view. The developed hydrogels exhibited desirable qualities of a drug delivery system that can be used for the delivery of the embedded polyanion.

Discovery and evaluation of 1H-pyrrolo[2,3-b]pyridine based selective and reversible small molecule BTK inhibitors for the treatment of rheumatoid arthritis.

In a pursuit to identify reversible and selective BTK inhibitors, two series based on 7H-pyrrolo[2,3-d]pyrimidine and 1H-pyrrolo[2,3-b]pyridine as the hinge binding core, have been identified. Structure activity relationship (SAR) exploration led to identification of two advanced lead molecules, 11 and 13, which demonstrated desired BTK inhibitory potency in different cellular assays, excellent selectivity in a panel of 50 diverse kinases, favorable in vivo PK properties in mice and anti-arthritic effect in a mouse model of CIA.

Geriatric assessment of older patients with cancer in Australia--a multicentre audit.

OBJECTIVE: The aim of this study is to determine the frequency of geriatric assessment in patients aged over 70 years in Australian medical oncology clinics. MATERIAL AND METHODS: This was a multicentre audit in two parts: a retrospective file review of initial consultations with an oncologist and prospective audit of case presentations at multidisciplinary meetings (MDMs). Patients aged over 70 years presenting to a medical oncology clinic or being discussed at an MDM were eligible. Data was collected at six oncology centres in Victoria, NSW and Canberra from October 2009 to March 2010. RESULTS: Data was collected from 251 file reviews and 108 MDM discussions in a total of 304 patients. Median age was 76 years (range 70-95). The geriatric assessment (GA) domains most frequently assessed during an initial consultation were the presence of comorbidities (92%), social situation-living alone or with someone (80%), social supports (63%), any mention of at least one Activity of Daily Living (ADL) (50%) and performance status (49%). Less frequently assessed were any Instrumental Activity of Daily Living (IADL) (26%), presence of a geriatric syndrome (24%), polypharmacy (29%) and creatinine clearance (11%). Only one patient had all components of ADLs and IADLs assessed. During MDMs all the geriatric domains were comparatively less frequently assessed. No patients had all ADL and IADL components discussed formally in an MDM. CONCLUSION: This is the first multicentre audit that reveals the low rates of GA in Australian medical oncology practice and describes the GA domains considered important by oncology clinicians.

Encapsulation and stabilization of polyoxometalates in self-assembled supramolecular hydrogels.

We have encapsulated the polyoxoanions [P2W18O62](6-) and [P2W15V3O62](9-) in a self-assembled carboxy-methyl-chitosan (CMC) hydrogel, exhibiting a regular superstructure in water at physiological pH. We performed stability studies as a function of temperature and polyoxometalate (POM) loading, and observed exceptional Tgel properties. This work is a step forward towards developing biologically active polyoxometalate-based materials.

Evaluation of brimonidine-timolol fixed combination in patients of primary open-angle glaucoma.

The aim of present study was to compare the efficacy and safety of fixed combination of brimonidine and timolol with individual components used as monotherapy in patients of primary open angle glaucoma. Patients were randomly assigned to receive brimonidine or timolol or brimonidine-timolol fixed combination, with 30 patients in each group. The mean reduction in intraocular pressure in brimonidine, timolol, and brimonidine-timolol group were 4.29 ± 1.97 mm Hg, 4.34 ± 1.21 mm Hg, and 5.54 ± 1.87 mm Hg respectively at 2 weeks and 4.86 ± 1.16 mm Hg, 5.42 ± 1.50 mm Hg, and 7.36 ± 2.58 mm Hg respectively at 6 weeks. When values of mean reduction in intraocular pressure were compared between brimonidine-timolol fixed combination with brimonidine and timolol, it was found to be statistically significant ( P < 0.05) at 2 weeks and highly significant (0.001) at 6 weeks. The overall frequency of adverse effects was similar in all three groups.

Fiber-coupled ultraviolet planar laser-induced fluorescence for combustion diagnostics.

Multimode silica step-index optical fibers are examined for use in planar laser-induced fluorescence (PLIF) for combustion diagnostics using ultraviolet (UV) laser sources. The multimode step-index fibers are characterized at UV wavelengths by examining their energy damage thresholds and solarization performance. The beam quality achievable with large clad step-index multimode fibers is also studied. Emphasis is placed on simultaneously achieving high output energy and beam quality (low output M(2)). The use of multimode fibers to deliver UV pulses at 283 nm for PLIF measurements of OH radicals in a Hencken burner is demonstrated. The fiber delivery capability of UV light will benefit combustion diagnostics in hostile environments, such as augmentor and combustor rigs.

Pillar height dependent formation of unprecedented Pd8 molecular swing and Pd6 molecular boat via multicomponent self-assembly.

Three-component self-assembly of a cis-blocked 90° Pd(II) acceptor with a mixture of a tetraimidazole and a linear dipyridyl donor self-discriminated into unusual Pd(8) molecular swing (1) and Pd(6) molecular boat (2), which are characterized by single-crystal X-ray diffraction analysis; their ability to bind C(60) in solution is established by fluorescence titration.

Self-assembly of metallamacrocycles using a dinuclear organometallic acceptor: synthesis, characterization, and sensing study.

A dinuclear organometallic acceptor 4,4'-bis[trans-Pt(PEt(3))(2)(O(3)SCF(3))(ethynyl)]biphenyl (1) containing Pt-ethynyl functionality is synthesized. Multinuclear NMR ((1)H, (31)P, and (13)C), infrared (IR), and electrospray ionization mass spectrometry (ESI-MS) including single-crystal X-ray diffraction analysis established the formation of 1. Equimolar treatment of acceptor 1 separately with three different "clip" type ditopic donors (L(a)-L(c)) yielded [2 + 2] self-assembled three metallamacrocycles 2a-2c, respectively. These macrocycles were characterized by various spectroscopic techniques, and their sizes/shapes were obtained through geometry optimization using molecular mechanics universal force field (MMUFF) simulations. Attachment of unsaturated ethynyl functionality to biphenyl building unit helped to make the macrocycles (2a-2c) π-electron rich and thereby fluorescent in nature. Furthermore, 2c in solution has been examined to be suitable for sensing electron-deficient nitroaromatic like picric acid, which is often considered as a secondary chemical explosive. The fluorescence study of 2c showed a marked quenching of initial emission intensity upon titrating with picric acid (PA), and it exhibited the largest fluorescence quenching response with high selectivity among various other electron deficient aromatic compounds tested.

Evaluation of efficacy and safety of orlistat in obese patients.

CONTEXT: Rapidly rising prevalence of obesity is alarming. Obesity predisposes to co-morbidities like hypertension, type 2 diabetes mellitus, dyslipidemias, thus substantially rising healthcare expenditure. Lifestyle modifications alone have very limited success, necessitating the addition of pharmacotherapy to it. OBJECTIVE: Present study was carried out to evaluate the efficacy and safety of orlistat in obese patients. MATERIALS AND METHODS: Eighty obese (BMI>30) patients according to inclusion and exclusion criteria were randomized into either of the two groups. Group 1 received orlistat 120 mg three times a day and group 2 received placebo three times a day. Weight, waist circumference, BMI, total cholesterol, triglycerides, HDL, LDL were measured at baseline and then at 8(th), 16(th) and 24(th) week. ADR reported by patients were recorded. For safety evaluation various hematological and biochemical parameters were assessed. Z test was used for analysis of data. RESULTS: Compared to placebo, orlistat caused significant reduction (P<0.05) in weight (4.65 kg vs 2.5 kg; orlistat vs placebo, respectively), BMI (1.91 kg/m(2) vs 0.64 kg/m(2)) and waist circumference (4.84 cm vs 2 cm), cholesterol (10.68 mg vs 6.18 mg) and LDL level (5.87 mg vs 2.33 mg). In the orlistat group, the GI side effects like loose stools, oily stools/spotting, abdominal pain and fecal urgency were observed. CONCLUSION: Orlistat is an effective and well-tolerated antiobesity drug, which can be employed as an adjunct to therapeutic lifestyle changes to achieve and maintain optimal weight.

Mode coupling and output beam quality of 100-400 µm core silica fibers.

Propagation and mode coupling within relatively short (∼1-10 m) large core, nominally multimode, fibers are of interest in a number of applications. In this research, we have studied the output beam quality and mode coupling in various fibers with core diameters of 100-400 µm and lengths of 2 m. Output beam quality (M2) and mode-coupling coefficients (D) have been studied for different clad dimensions, numerical apertures, and wavelengths. The mode-coupling coefficients have been determined based on modal power diffusion considerations. The results show that D scales approximately as the inverse square of the clad dimension and inverse square root of the wavelength. Output from a 2 m length fiber of 100 µm core and 660 µm clad fiber is close to single mode (M2=1.6), while output from a 200 µm core and 745 µm clad fiber also has high beam quality.

Laser-induced breakdown spectroscopy for in-cylinder equivalence ratio measurements in laser-ignited natural gas engines.

In this contribution we present the first demonstration of simultaneous use of laser sparks for engine ignition and laser-induced breakdown spectroscopy (LIBS) measurements of in-cylinder equivalence ratios. A 1064 nm neodynium yttrium aluminum garnet (Nd:YAG) laser beam is used with an optical spark plug to ignite a single cylinder natural gas engine. The optical emission from the combustion initiating laser spark is collected through the optical spark plug and cycle-by-cycle spectra are analyzed for H(alpha)(656 nm), O(777 nm), and N(742 nm, 744 nm, and 746 nm) neutral atomic lines. The line area ratios of H(alpha)/O(777), H(alpha)/N(746), and H(alpha)/N(tot) (where N(tot) is the sum of areas of the aforementioned N lines) are correlated with equivalence ratios measured by a wide band universal exhaust gas oxygen (UEGO) sensor. Experiments are performed for input laser energy levels of 21 mJ and 26 mJ, compression ratios of 9 and 11, and equivalence ratios between 0.6 and 0.95. The results show a linear correlation (R(2) > 0.99) of line intensity ratio with equivalence ratio, thereby suggesting an engine diagnostic method for cylinder resolved equivalence ratio measurements.