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Patients these days are increasingly conscious of personal appearance, and much attention is being focused on the smile. Cosmetic dentistry is also in the race to become the most advanced and demanding dental subspecialty. Recently, aesthetic lip surgeries have been introduced, like lip repositioning, lip reduction and lip enhancement surgeries, to improve facial aesthetics. The authors present a case of a 28-year-old healthy male who reported to the Department of Periodontics with the chief complaint of poor aesthetics and large lips. His lower lip was double the size of the upper lip. Therefore, an aesthetic lip reduction surgery was planned. The lip reduction operation could successfully manage the large lower lip with no intra or postoperative complications. No recurrence was observed within a period of 12 months. Cheiloplasty balances the look of the top and lower lips, improving the appearance of the face as a whole.

IntroductionAlzheimer’s Disease (AD) typically starts in the medial temporal lobe, then develops into a neurodegenerative cascade which spreads to other brain regions. People with subjective cognitive decline (SCD) are more likely to develop dementia, especially in the presence of amyloid pathology. Thus, we were interested in the white matter microstructure of the medial temporal lobe in SCD, specifically the lower cingulum bundle that leads into the hippocampus. Diffusion tensor imaging (DTI) has been shown to differentiate SCD participants who will progress to mild cognitive impairment from those who will not. However, the biology underlying these DTI metrics is unclear, and results in the medial temporal lobe have been inconsistent.MethodsTo better characterize the microstructure of this region, we applied DTI to cognitively normal participants in the Cam-CAN database over the age of 55 with cognitive testing and diffusion MRI available (N = 325, 127 SCD). Diffusion MRI was processed to generate regional and voxel-wise diffusion tensor values in bilateral lower cingulum white matter, while T1-weighted MRI was processed to generate regional volume and cortical thickness in the medial temporal lobe white matter, entorhinal cortex, temporal pole, and hippocampus.ResultsSCD participants had thinner cortex in bilateral entorhinal cortex and right temporal pole. No between-group differences were noted for any of the microstructural metrics of the lower cingulum. However, correlations with delayed story recall were significant for all diffusion microstructure metrics in the right lower cingulum in SCD, but not in controls, with a significant interaction effect. Additionally, the SCD group showed an accelerated aging effect in bilateral lower cingulum with MD, AxD, and RD.DiscussionThe diffusion profiles observed in both interaction effects are suggestive of a mixed neuroinflammatory and neurodegenerative pathology. Left entorhinal cortical thinning correlated with decreased FA and increased RD, suggestive of demyelination. However, right entorhinal cortical thinning also correlated with increased AxD, suggestive of a mixed pathology. This may reflect combined pathologies implicated in early AD. DTI was more sensitive than cortical thickness to the associations between SCD, memory, and age. The combined effects of mixed pathology may increase the sensitivity of DTI metrics to variations with age and cognition.

Regenerating periodontal tissue is the main goal of periodontal therapy. Periodontal tissue regeneration involves the development of new bone, cement, and periodontal ligaments on damaged tooth root surfaces in order to restore anatomy and function. In order to further enhance PRF (Platelet rich fibrin) and develop advanced platelet-rich fibrin, a slower rotating speed is proposed (A-PRFs). Cell dispersion is affected by centrifugation rate. The majority of the leukocytes in the PRF are concentrated near the bottom of the tube due to centrifugation rate. By switching the centrifugation process to 1,500 rpm for 14 minutes, granulocyte neutrophils and the fibrin matrix are more evenly distributed in the A-PRF created. Hence, a periodontal evaluation of this subject is required.

Households, restaurants, canteens, and hotel wastes constitute kitchen waste. Every day our growing cities generate more and more waste, which is overloading our municipal systems. The main aim of the present work was to prepare a microbial consortium that can effectively and rapidly bring about the degradation of kitchen wastes that can be used in agricultural soils. More than 100 different bacterial isolates were obtained from various kitchen waste dumping areas. The bacterial isolates were studied to produce enzymes like amylase, gelatinase, lipase, and protease on respective media plates. The best 20 isolates were subjected to enzyme quantification. The isolates showing maximum production for all four enzymes were selected for consortia preparation. The consortia of isolates were prepared by permutation combinations. Amongst all consortia prepared consortium No. 7 showed maximum enzymatic potential. The bacterial isolates in the best consortium (No. 7) were further characterized and identified as KW104 Serratia marcescens, KW37 Micrococcus luteus, KW128 Brevindimonas mediterranea, KW91 Bacillus tequilensis, and KW97 Exiguobacterium mexicanum. This consortium showed rapid degradation of waste as compared to others in 15 days duration of time showing good potential for compost formation when applied to plant growth.

False smut of rice (Oryza sativa L.) caused by Ustilaginoidea virens (Cooke) Takah., 1896 is an important emerging disease of rice. An experiment was conducted during 2018–19 and 2019–20 at Institute of Agricultural Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh to study the U. virens prevalence and morphological variability in northern India with the effect of weather variables on the percentage disease incidence (PDI) of false smut of rice. The study revealed that the false smut incidence was higher in Varanasi district of Uttar Pradesh (53.64%). The lowest percentage (20.68–27.55%) of infected tillers was found in Kangra district of Himachal Pradesh, and Tehri Garhwal district of Uttarakhand. The grain replacement percentage was highest in the Moti cultivar (51.17%), while the highest yield loss percentage was in the Pusa Basmati (57.11 %) variety. The majority of the isolates in our investigation had fluffy, raised, and irregular colony morphology. The correlation between the false smut disease incidence and weather has been evaluated in the Varanasi district, and found that the temperature of 20.36°C with an RH of 85.13% and low rainfall of 8.92 mm was conducive to disease initiation and positively correlated with the PDI. Other epiphytotic factors like sunshine hours, and wind speed were all found to be negatively linked with PDI. In this investigation, for the first time, the viability of spores was also checked. It was found that 2-year-old spores were not viable because they did not retain any Brilliant Cresyl blue colour dye, which stains the stored food material in spores, while 1-month-old spores were found to be 100% viable. All the isolates were further confirmed with the specific ITS marker.

The aye-aye (Daubentonia madagascariensis) is a nocturnal lemur native to the island of Madagascar with a unique thin middle finger. Its slender third digit has a remarkably specific adaptation, allowing them to perform tap-scanning to locate small cavities beneath tree bark and extract wood-boring larvae from it. As an exceptional active acoustic actuator, this finger makes an aye-aye’s biological system an attractive model for pioneering Nondestructive Evaluation (NDE) methods and robotic systems. Despite the important aspects of the topic in the aye-aye’s unique foraging and its potential contribution to the engineering sensory, little is known about the mechanism and dynamics of this unique finger. This paper used a motion-tracking approach for the aye-aye’s middle finger using simultaneous video graphic capture. To mimic the motion, a two-link robot arm model is designed to reproduce the trajectory. Kinematics formulations were proposed to derive the motion of the middle finger using the Lagrangian method. In addition, a hardware model was developed to simulate the aye-aye’s finger motion. To validate the model, different motion states such as trajectory paths and joint angles, were compared. The simulation results indicate the kinematics of the model were consistent with the actual finger movement. This model is used to understand the aye-aye’s unique tap-scanning process for pioneering new tap-testing NDE strategies for various inspection applications.

Dental implant treatment is turning into a widely accepted and popular treatment option for patients. With the growing era of dental implant therapy, complications and failures have also become common. Such intricacies are becoming a vexing issue for clinicians as well as patients. Implant failures can be due to mechanical or biological reasons. Failure of osseointegration of the implant falls under biological failures, whereas mechanical complications include fracture of the implant, framework or prosthetic components. Diligently observing the implant after placement is the first step in managing the declining circumstances. It is important to have a thorough understanding of how and why implants fail to achieve successful treatment outcomes in the long run. In dentistry, nanoparticles are used to make antibacterial chemicals that improve dental implants. They can be used in conjunction with acrylic resins for fabricating removable dentures during prosthetic treatments, composite resins for direct restoration during restorative treatments, endodontic irrigants and obturation materials during endodontic procedures, orthodontic adhesives and titanium coating during dental implant procedures. This article aimed to review the etiological factors that lead to implant failure and their solutions.

Growth promoting Rhizobium spp are frequently used as biofertilizers for agricultural cropping system. Furthermore, Isolation, screening and biochemical characterization of Rhizobium for a specific plant is necessary to examine ability of isolated bacteria to affect the growth and development of host plant in various ways. The current study was aimed to isolate plant specific rhizobacterial strains which are compatible with lentil (Lens culinaris Medik.L.) plant. 20 bacterial isolates have been isolated from root nodules of lentil from various agro ecological area and their biochemical characterization was performed by different plant growth promotion activities. The result showed that, among 20 isolates, four isolates have vigorous plant growth promoting activities. Four bacterial strains were able to solubilise phosphorous along with hormone production. Moreover, among four bacterial strains, two strongly produced HCN and siderophore in vitro. Subsequently, all selected bacterial isolates were inoculated in lentil seeds of variety HUL57 to study germination percentage and vigour index of the crop. Out of four isolates 26N isolate performed best growth promotion activities on lentil seedlings. Finally, on the basis of performance of bacteria on plant, four isolates were characterized using molecular approach of species identification such as 16S rRNA sequencing.

GABAergic inhibitory neurons are the principal source of inhibition in the brain. Traditionally, their role in maintaining the balance of excitation-inhibition has been emphasized. Beyond homeostatic functions, recent circuit mapping and functional manipulation studies have revealed a wide range of specific roles that GABAergic circuits play in dynamically tilting excitation-inhibition coupling across spatio-temporal scales. These span from gating of compartment- and input-specific signaling, gain modulation, shaping input–output functions and synaptic plasticity, to generating signal-to-noise contrast, defining temporal windows for integration and rate codes, as well as organizing neural assemblies, and coordinating inter-regional synchrony. GABAergic circuits are thus instrumental in controlling single-neuron computations and behaviorally-linked network activity. The activity dependent modulation of sensory and mnemonic information processing by GABAergic circuits is pivotal for the formation and maintenance of episodic memories in the hippocampus. Here, we present an overview of the local and long-range GABAergic circuits that modulate the dynamics of excitation-inhibition and disinhibition in the main output area of the hippocampus CA1, which is crucial for episodic memory. Specifically, we link recent findings pertaining to GABAergic neuron molecular markers, electrophysiological properties, and synaptic wiring with their function at the circuit level. Lastly, given that area CA1 is particularly impaired during early stages of Alzheimer’s disease, we emphasize how these GABAergic circuits may contribute to and be involved in the pathophysiology.

Purpose: In Dynamic contrast-enhanced MRI (DCE-MRI), Arterial Input Function (AIF) has been shown to be a significant contributor to uncertainty in the estimation of kinetic parameters. This study is to assess the feasibility of using a deep learning network to estimate local Capillary Input Function (CIF) to estimate blood-brain barrier (BBB) permeability, while reducing the required scan time. Materials and Method: A total of 13 healthy subjects (younger ( 67 y/o): 5) were recruited and underwent 25-min DCE-MRI scans. The 25 min data were retrospectively truncated to 10 min to simulate a reduced scan time of 10 min. A deep learning network was trained to predict the CIF using simulated tissue contrast dynamics with two vascular transport models. The BBB permeability (PS) was measured using 3 methods: (i) Ca-25min, using DCE-MRI data of 25 min with individually sampled AIF (Ca); (ii) Ca-10min, using truncated 10min data with AIF (Ca); and (iii) Cp-10min, using truncated 10 min data with CIF (Cp). The PS estimates from the Ca-25min method were used as reference standard values to assess the accuracy of the Ca-10min and Cp-10min methods in estimating the PS values. Results: When compared to the reference method(Ca-25min), the Ca-10min and Cp-10min methods resulted in an overestimation of PS by 217 ± 241 % and 48.0 ± 30.2 %, respectively. The Bland Altman analysis showed that the mean difference from the reference was 8.85 ± 1.78 (x10−4 min−1) with the Ca-10min, while it was reduced to 1.63 ± 2.25 (x10−4 min−1) with the Cp-10min, resulting in an average reduction of 81%. The limits of agreement also reduced by up to 39.2% with the Cp-10min. We found a 75% increase of BBB permeability in the gray matter and a 35% increase in the white matter, when comparing the older group to the younger group. Conclusions: We demonstrated the feasibility of estimating the capillary-level input functions using a deep learning network. We also showed that this method can be used to estimate subtle age-related changes in BBB permeability with reduced scan time, without compromising accuracy. Moreover, the trained deep learning network can automatically select CIF, reducing the potential uncertainty resulting from manual user-intervention.

Abstract Early diagnosis of Alzheimer’s disease plays a pivotal role in patient care and clinical trials. In this study, we have developed a new approach based on 3D deep convolutional neural networks to accurately differentiate mild Alzheimer’s disease dementia from mild cognitive impairment and cognitively normal individuals using structural MRIs. For comparison, we have built a reference model based on the volumes and thickness of previously reported brain regions that are known to be implicated in disease progression. We validate both models on an internal held-out cohort from The Alzheimer's Disease Neuroimaging Initiative (ADNI) and on an external independent cohort from The National Alzheimer's Coordinating Center (NACC). The deep-learning model is accurate, achieved an area-under-the-curve (AUC) of 85.12 when distinguishing between cognitive normal subjects and subjects with either MCI or mild Alzheimer’s dementia. In the more challenging task of detecting MCI, it achieves an AUC of 62.45. It is also significantly faster than the volume/thickness model in which the volumes and thickness need to be extracted beforehand. The model can also be used to forecast progression: subjects with mild cognitive impairment misclassified as having mild Alzheimer’s disease dementia by the model were faster to progress to dementia over time. An analysis of the features learned by the proposed model shows that it relies on a wide range of regions associated with Alzheimer's disease. These findings suggest that deep neural networks can automatically learn to identify imaging biomarkers that are predictive of Alzheimer's disease, and leverage them to achieve accurate early detection of the disease.

Introduction: The idea of Full-Mouth Disinfection (FMD) was presented in the early 1990s, the traditional method of treating periodontal disease, quadrant by quadrant over several visits. The FMD method has been recommended with a number of changes over time. Triphala, Ayurvedic medicinal herbal formulations is also useful in dentistry as antiplaque, antimicrobial, antioxidant, analgesic, antipyretic and anti-inflammatory agent. As Chlorhexidine (CHX) is used from past years for full mouth disinfection, there is need to evaluate the efficacy of CHX as well as Triphala in diabetic mellitus patients. Need of the study: As CHX has been used for years to disinfect the entire mouth, a study comparing the effectiveness of CHX and Triphala in individuals with Diabetes Mellitus (DM) for full mouth disinfection will be done. Aim: To evaluate and compare the efficacy of triphala and CHX in the treatment of Stage-II and III periodontitis with one stage complete mouth disinfection in Type-IIDM patients. Materials and Methods: This experimental study will be done in Sharad Pawar dental College, department of Periodontics after obtaining the ethical clearance during September 2021 to September 2022. About 24 type 2 diabetic subjects with Stage-II and Stage-III periodontitis, will be randomly divided into test Group-And control group with 12 in each group. In Group-A, Full mouth disinfection will be done using CHX and in Group-B full mouth disinfection will be done using Triphala. After full mouth subgingival scaling and root planning, patient will brush the dorsum of the tongue for one minute with gel, the mouth will be rinsed two times with mouthwash for one minute, the pharynx will be cleaned with a spray, and all periodontal pockets will be irrigated (thrice within 10 minutes) with a gel. Clinical parameters will be evaluated at baseline and six months. The clinical parameters are Probing Pocket Depth (PPD), Plaque Index (PI), Clinical Attachment Level (CAL), Papillary Bleeding Index (PBI). Paired t-test will be used to compare data within group for before and after treatment and unpaired t-test will be used to compare between the groups.

IntroductionAlzheimer’s disease (AD) and Lewy body disease (LBD) are the two most common neurodegenerative dementias and can occur in combination (AD+LBD). Due to overlapping biomarkers and symptoms, clinical differentiation of these subtypes could be difficult. However, it is unclear how the magnitude of diagnostic uncertainty varies across dementia spectra and demographic variables. We aimed to compare clinical diagnosis and post-mortem autopsy-confirmed pathological results to assess the clinical subtype diagnosis quality across these factors.MethodsWe studied data of 1,920 participants recorded by the National Alzheimer’s Coordinating Center from 2005 to 2019. Selection criteria included autopsy-based neuropathological assessments for AD and LBD, and the initial visit with Clinical Dementia Rating (CDR) stage of normal, mild cognitive impairment, or mild dementia. Longitudinally, we analyzed the first visit at each subsequent CDR stage. This analysis included positive predictive values, specificity, sensitivity and false negative rates of clinical diagnosis, as well as disparities by sex, race, age, and education. If autopsy-confirmed AD and/or LBD was missed in the clinic, the alternative clinical diagnosis was analyzed.FindingsIn our findings, clinical diagnosis of AD+LBD had poor sensitivities. Over 61% of participants with autopsy-confirmed AD+LBD were diagnosed clinically as AD. Clinical diagnosis of AD had a low sensitivity at the early dementia stage and low specificities at all stages. Among participants diagnosed as AD in the clinic, over 32% had concurrent LBD neuropathology at autopsy. Among participants diagnosed as LBD, 32% to 54% revealed concurrent autopsy-confirmed AD pathology. When three subtypes were missed by clinicians, “No cognitive impairment” and “primary progressive aphasia or behavioral variant frontotemporal dementia” were the leading primary etiologic clinical diagnoses. With increasing dementia stages, the clinical diagnosis accuracy of black participants became significantly worse than other races, and diagnosis quality significantly improved for males but not females.DiscussionThese findings demonstrate that clinical diagnosis of AD, LBD, and AD+LBD are inaccurate and suffer from significant disparities on race and sex. They provide important implications for clinical management, anticipatory guidance, trial enrollment and applicability of potential therapies for AD, and promote research into better biomarker-based assessment of LBD pathology.

Introduction: Alzheimer’s disease (AD) and cerebral small vessel disease (CVSD) both contribute to age-related cognitive decline but can be difficult to clinically distinguish at early stages. At mild cognitive impairment (MCI), we investigated brain MRI volumetric differences in white matter hyperintensities (WMH), frontal and temporal lobe volumes between neuropathologically defined groups of cerebral arteriolosclerosis alone (pARTE), AD alone (pAD), and mixed (ADARTE). Methods: From the National Alzheimer’s Coordinating Center, we defined neuropathology groups of pARTE (n = 18), pAD (n = 36), and ADARTE (n = 55) who had MRI brain volumetrics within 1 year of clinical evaluation with Clinical Dementia Rating score of 0.5, corresponding to MCI. We included moderate-to-severe arteriolosclerosis and/or ABC score 2–3 for AD, after excluding other major neuropathologies. We compared WMH and frontal and temporal lobe volumes between neuropathology groups using regression analysis. Results: Adjusted regression models show AD-related groups associated with less WMH when compared to pARTE (pAD adjusted odds ratio (aOR) (95% confidence interval [CI]): 0.94 (0.90–0.98); ADARTE aOR (95% CI): 0.96 (0.93–0.99)). The mixed pathology group, but not pAD, had smaller right temporal lobe volumes than pARTE (pAD aOR [95% CI]: 0.86 [0.74–1.00]; ADARTE aOR [95% CI]: 0.83 [0.72–0.96]). There were no differences in frontal lobe volumes. Discussion/Conclusions: Findings from this neuropathologically confirmed cohort suggest volumetric differences in WMH and temporal lobe volumes between AD- and CVSD-related MCI. Moreover, our results suggest a differential atrophy susceptibility of the right versus left temporal lobe to the additive effect of AD and vascular pathologies.

WRKY transcription factor (TF) family is well known to govern essential physiological functioning as well as regulate plant response to biotic and abiotic stress. In this study, we have identified 108 OsWRKY genes in the genome of Oryza sativa subsp. japonica, using the updated genomic data from the Rice Annotation Project Database and Oryzabase, which were further used to conduct the phylogenetic study, motif analysis, gene structure analysis, chromosomal mapping, and prediction of sub‐cellular localization. The multiple sequence alignment OsWRKY proteins revealed the presence of nine different types of alterations in the conserved heptapeptide sequence WRKYGQK associated with 19 OsWRKY genes. Physiochemical analysis discloses the hydrophobic amino acid‐rich, thermally stable, and polar nature of OsWRKY proteins. These genes were noted as highly conserved between the two cultivated sub‐species of Oryza sativa, that is Indica and japonica type. Additionally, from motif analysis, we have found a new motif, which was categorized as hAT family C‐terminal dimerization region associated with four members of group IIc. We have identified 21 stress‐responsive OsWRKY genes, and their significance to the different biotic and abiotic stress‐mediated cascades was further evaluated by analysing 1500 kb upstream sequences and this disclosed the presence of important phytohormone‐responsive cis‐elements in the OsWRKY gene, suggesting its direct involvement in defence against a wide range of external stressors and these 21 OsWRKY genes are tentatively listed as possible candidates for more study. [ABSTRACT FROM AUTHOR]

Aim: To describe patient and treatment characteristics associated with bevacizumab BS-Pfizer, rituximab BS-Pfizer and trastuzumab BS-Pfizer and their reference products in Japan. Methods: This retrospective observational study used an administrative claims database to identify patients with ≥1 biosimilar or reference product prescription from 2019 to 2022 for approved indications. Descriptive statistics were calculated. Results: Overall, 14–39% of biosimilar-prescribed patients initiated therapy with reference products. Biosimilar utilization significantly increased from 2019 to 2022. The most-commonly prescribed concomitant class of therapy with biosimilars was antineoplastic therapy. Conclusion: Reference products were most frequently prescribed among the Japanese cohorts, but substantial and increasing proportions received biosimilars over time. Future studies should extend our initial insights to assess biosimilar clinical outcomes in Japanese settings. Plain Language Summary This study examines the adoption of cancer biosimilar therapies in Japan from 2019 to 2022. Cancer biosimilars are complex treatments that closely resemble established cancer therapies already available in Japan. We looked into the characteristics of patients receiving three specific biosimilars – bevacizumab BS-Pfizer, rituximab BS-Pfizer and trastuzumab BS-Pfizer. We also investigated where patients received biosimilar treatment, other therapies they received alongside biosimilars and the proportion of patients using these therapies each year during the study. Our analysis utilized data from the 'Medical Data Vision' database, which records care provided in hospitals across Japan. We analyzed patient demographics and treatment patterns, and compared different groups using statistics to identify significant differences. Notably, we observed that between 14 and 39% of patients initially started treatment with the original version of the drug on the market, known as the 'reference product,' before switching to the biosimilar. Furthermore, our findings revealed a significant increase in the use of biosimilars each year during the study period. Biosimilars were most-commonly used alongside chemotherapy drugs. These initial findings shed light on the patient population using cancer biosimilars in Japan and the treatment contexts in which they are utilized. Future research should delve deeper into aspects such as cost of care, patient survival, side effects and other pertinent factors related to the use of biosimilars in cancer care in Japan. Article highlights The use of oncology biosimilars in clinical practice in Japan is limited, at least partly, by the lack of evidence demonstrating real-world outcomes in Japanese patients. This retrospective observational study provides descriptive insights into the real-world use of bevacizumab, rituximab and trastuzumab biosimilars in Japan for colorectal cancer and non-small-cell lung cancer, B-cell non-Hodgkin's lymphoma and HER2-positive breast and gastric cancers, respectively. We observed significant increases in biosimilar utilization over time from 2019 to 2022. Across indications, from 14 to 39% of biosimilar-prescribed patients switched to the biosimilar after initiating therapy with the corresponding refence product. The most commonly prescribed concomitant class of therapy with biosimilars was antineoplastic therapy across each setting. This study has several limitations that should be noted, including that the Medical Data Vision hospital-based claims database has missing data for some variables, lacks detailed diagnosis and prognosis data (histology, Eastern Cooperative Oncology Group performance status, disease severity, etc.) and does not record deaths that occur outside the hospital. Initial real-world insights in Japan demonstrate comparable patient characteristics, treatment patterns and treatment duration between bevacizumab, rituximab and trastuzumab biosimilar and originator-treated patients. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a devastating, age‐associated neurodegenerative disorder and the most common cause of dementia. The clinical continuum of AD spans from preclinical disease to subjective cognitive decline, mild cognitive impairment, and dementia stages (mild, moderate, and severe). Neuropathologically, AD is defined by the accumulation of amyloid β (Aβ) into extracellular plaques in the brain parenchyma and in the cerebral vasculature, and by abnormally phosphorylated tau that accumulates intraneuronally forming neurofibrillary tangles (NFTs). Development of treatment approaches that prevent or even reduce the cognitive decline because of AD has been slow compared to other major causes of death. Recently, the United States Food and Drug Administration gave full approval to 2 different Aβ‐targeting monoclonal antibodies. However, this breakthrough disease modifying approach only applies to a limited subset of patients in the AD continuum and there are stringent eligibility criteria. Furthermore, these approaches do not prevent progression of disease, because other AD‐related pathologies, such as NFTs, are not directly targeted. A non‐mutually exclusive alternative is to address lifestyle interventions that can help reduce the risk of AD and AD‐related dementias (ADRD). It is estimated that addressing such modifiable risk factors could potentially delay up to 40% of AD/ADRD cases. In this review, we discuss some of the many modifiable risk factors that may be associated with prevention of AD/ADRD and/or increasing brain resilience, as well as other factors that may interact with these modifiable risk factors to influence AD/ADRD progression. [Color figure can be viewed at www.annalsofneurology.org] ANN NEUROL 2024;96:633–649 [ABSTRACT FROM AUTHOR]

AbstractBackgroundMethodsResultsConclusion\nPLAIN LANGUAGE SUMMARYCyclin-dependent kinase 4/6 (CDK 4/6) inhibitors have emerged as a significant advancement in the treatment of HR+/HER2− metastatic breast cancer (MBC). Despite the clinical efficacy of CDK 4/6 inhibitors in HR+/HER2− metastatic breast cancer, there remains a significant gap in understanding their cost-effectiveness, particularly regarding the long-term economic impact and the key drivers of costs, when used in combination with endocrine therapy. This study aims to systematically review and conduct a meta-analysis of cost-effectiveness studies evaluating CDK4/6 inhibitors in treatment of HR+/HER2− advanced breast cancer and identify key drivers of costs of CDK4/6 inhibitors in combination with endocrine therapy.A comprehensive search of PubMed and Embase was conducted to identify peer-reviewed studies from February 2015 to March 2022 reporting cost-effectiveness of CDK4/6 inhibitors in MBC treatment. Incremental net benefits (INBs) were estimated, and meta-analysis was conducted. This review adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.We identified 120 articles, of which 18 were eligible for systematic review and 16 for meta-analysis. None of the three CDK4/6 inhibitors had positive INB compared to endocrine/aromatase inhibitors therapy alone. The pooled INB was estimated at −$149,266.87 (95% Confidence Interval (CI) = −$196,961.54, −$101,572.20).The combination of CDK4/6 inhibitors and letrozole/endocrine therapy for the treatment of postmenopausal patients with advanced HR+/HER2 − MBC was not cost-effective.Breast cancer, a significant health concern worldwide, represents around 30% of new cancer diagnoses and 25% of cancer related fatalities. Among these cases, approximately two-thirds are characterized by hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) tumors. In the metastatic stage, up to half of patients exhibit inherent resistance to endocrine therapy, leading to poorer survival rates, while others, initially responsive, eventually develop resistance, leading to disease progression and eventual mortality. Nevertheless, recent advancements in CDK4/6 inhibitors have shown efficacy in overcoming both inherent and acquired endocrine resistance, representing a substantial breakthrough in HR+/HER2− metastatic breast cancer treatment. This study conducts a review of literature focusing on comparative cost-effectiveness and economic evaluations of the three CDK4/6 inhibitors, evaluating the pooled incremental net benefit (INB) reported in these studies. It marks the first attempt to compare all three CDK4/6 inhibitors and employs a meta-analysis approach to ascertain the option demonstrating the most positive INB. Our findings indicate that CDK4/6 inhibitors fail to provide an economic advantage over letrozole or endocrine therapy alone. The aim of this study is to offer insights for clinical and reimbursement decision-making in the treatment of postmenopausal patients with advanced HR+/HER2− breast cancer, providing valuable guidance for policymakers, payers, and clinicians. [ABSTRACT FROM AUTHOR]

The glycosaminoglycan Hyaluronic Acid (HA) is present in the connective tissue of vertebrates. In the extracellular matrix of soft periodontal tissues, it is the most prevalent glycosaminoglycan with a higher molecular weight. In medical fields such as orthopaedics, dermatology, and ophthalmology, the use of HA in the treatment of inflammatory processes is well established. The extracellular matrix of various tissues, including connective tissue, synovial fluid, and other tissues, contains HA, a naturally occurring linear polysaccharide. Its efficacy in the treatment of inflammatory conditions has been proven. It has anti-inflammatory and anti-bacterial effects in the treatment of gingivitis and periodontitis in dentistry. It could be used as an adjunct to mechanical therapy in the treatment of periodontitis because of its tissue healing properties. Use of HA for implant surface modification has also been extensively studied. HA has proven to be effective in peri-implantitis. The purpose of this review paper is to explain HA’s involvement in periodontal therapy.

Introduction: The goals of periodontal therapy include preventing illness, slowing or stopping disease development, replacing lost periodontal tissues, and preserving the therapeutic outcomes. The apical repositioning of the gingival edge during traditional periodontal surgery exposes the root surface to the oral cavity and reduces pocket depth. It may lead to attachment loss, Gingival Recession (GR). It is also commonly recognised that periodontal surgery causes pain and suffering. Laser assisted periodontal therapy has been the subject of study in an effort to address these drawbacks. Aim: To compare the efficacy of diode laser as an adjunct to Open Flap Debridement (OFD) with that of OFD alone in the management of chronic periodontitis patients. Materials and Methods: This randomised clinical trial with split mouth study design will be conducted in Periodontics Department at Sharad Pawar Dental College, Wardha, Maharashtra, India, for a duration of six months. Thirteen patients (26 quadrants) with generalised chronic periodontitis patients will be selected. The Probing Pocket Depth (PPD) ≥5 mm after phase I therapy will be included in this split mouth study. Diode laser (920 nm) will be used as an adjunct to OFD (test) as compared with conventional flap surgery (control). Clinical parameters like Plaque Index (PI), Papillary Bleeding Index (PBI), PPD, Relative Attachment Level (RAL) and Relative Gingival Marginal Level (RGML) and GR will be recorded at baseline and six months post-therapy. Visual Analogue Scale (VAS) will be used to determine patient discomfort intraoperatively and after one week. A questionnaire for patient-based outcomes will be administered after period of six months postsurgery and response will be recorded. Student’s paired t-test will be used for comparing the treatment groups at baseline and six months.

Demyelination is observed in both healthy aging and age-related neurodegenerative disorders. While the significance of myelin within the cortex is well acknowledged, studies focused on intracortical demyelination and depth-specific structural alterations in normal aging are lacking. Using the recently available Human Connectome Project Aging dataset, we investigated intracortical myelin in a normal aging population using the T1w/T2w ratio. To capture the fine changes across cortical depths, we employed a surface-based approach by constructing cortical profiles traveling perpendicularly through the cortical ribbon and sampling T1w/T2w values. The curvatures of T1w/T2w cortical profiles may be influenced by differences in local myeloarchitecture and other tissue properties, which are known to vary across cortical regions. To quantify the shape of these profiles, we parametrized the level of curvature using a nonlinearity index (NLI) that measures the deviation of the profile from a straight line. We showed that NLI exhibited a steep decline in aging that was independent of local cortical thinning. Further examination of the profiles revealed that lower T1w/T2w near the gray-white matter boundary and superficial cortical depths were major contributors to the apparent NLI variations with age. These findings suggest that demyelination and changes in other T1w/T2w related tissue properties in normal aging may be depth-specific and highlight the potential of NLI as a unique marker of microstructural alterations within the cerebral cortex.

A 22-year-old female patient reported to the Department of Periodontics with a chief complaint of swollen gums in the lower front jaw region since six months, not associated with pain. Patient was apparently alright six months back, then she noticed a small growth in the mandibular anterior region of jaw. Patient gave a history of trauma six months back, at the same region due to fall on stairs. The condition was causing difficulty in mastication and poor aesthetics. The growth was sluggish at first, then progressed slowly until it reached its current size of 15×10 mm intraorally, with no extraoral swelling. In regard to tooth numbers 31, 32, 33 and the growth was pink in colour, firm, clearly defined, mobile, pedunculated, non pulsating, and smooth surfaced [Table/Fig-1,2]. The swelling was not associated with tenderness. Generalised bleeding on probing was present. Based on history and clinical features the growth was provisionally diagnosed as generalised chronic gingivitis with gingival fibroma. Differential diagnosis were gingival epulis, Pyogenic Granuloma (PG), peripheral ossifying fibroma, traumatic fibroma, peripheral giant cell granuloma, haemangioma and metastatic cancer. The patient was informed about the growth and the treatment options were explained such as such as excision of overgrowth using scalpel, cautery and lasers. Prior to treatment, informed consent was obtained from the patient. The results of blood tests such as haemoglobin (12.8 gm%), bleeding time (1 minute and 30 seconds) and clotting time (2 minutes) were all within acceptable and physiological limits. Under local anaesthesia (Lignox 2% with Adrenaline- 1:80000), the overgrowth was slightly elevated with the help of floss to determine the base or attachment of the overgrowth on gingiva [Table/Fig-3]. The growth was entirely excised from its base using a soft tissue 920 mm diode laser (BIOLASE) in pulse mode with protective armamentarium. During surgery, the fiber’s tip came into contact with the borders of the lesion [Table/Fig-4,5]. Proper scalloping of the gingival margins was done [Table/Fig-6]. There was no suturing done. Periodontal pack was applied [Table/Fig-7]. Brufen 400 mg was prescribed from the day of operation three times a day for three days as a postoperative medicine. The patient was given instructions that included, caring for the surgery site, eating soft diet for one day and maintaining good dental hygiene including brushing at non surgical site twice daily and use of chlorhexidine mouthwash twice daily [Table/Fig-8]. Following the surgery, the patient experienced no pain or discomfort. There was no sign of the lesion at recall visit. The tissue was sent for histological examination after the complete surgical removal of the lesion. Haematoxyllin and Eosin (H&E) stained tissue section showed lesional connective tissue stroma. It comprised of densely packed parallely arranged collagen fibres. At places, these collagen fibers are haphazardly arranged. The fibroblasts showed spindle shaped elongated nuclei. Severe chronic inflammatory cell infiltration was seen, suggestive of fibroma [Table/Fig-9]. Fibroma is the most frequent benign development in the mouth cavity [1]. Traumatic fibroma is a frequent, benign and slow growing, soft tissue tumour [2]. This mass is normally asymptomatic and increases in size over time [3]. These lesions can be caused by irritants such as plaque, calculus, overhanging edges, and restorations. Fibroma can develop as a result of an injury or local inflammation caused by fibrous hyperplasia [4]. A histologic examination of the lesion, can help rule out other benign and malignant fibroma-like tumours. Irritation fibromas, according to Arya S et al., and, Barker DS and Lucas RB, expressed two patterns of collagen arrangements, namely (a) radiating pattern and (b) circular pattern, depending on the site and level of irritation experienced by the lesion [2,3]. As a result, the authors concluded that static areas with greater stress, such as the palate, produced radiating patterns, but flexible areas (such as the buccal mucosa) with less trauma caused circular patterns [3]. According to Gupta D et al., true fibromas did not show this pattern [4]. Surgical excision is commonly used to treat fibroma, and recurrence is unlikely unless the source of irritation/trauma is entirely eradicated. Women account for 66% of all bothersome fibromas. It is unusual in the first 10 years of life. It is possible that the lesion is sessile or has a pedunculated base and it normally grows slowly over several months to reach its maximum size. The highest size is rarely more than 1.5 cm [5]. The lesion in the present case, however, was significantly greater in comparison. In the absence of malignant change, it is usually self-limiting. On the other hand, long term surveillance is essential to detect transformation and recurrence of such lesions [5]. The laser employed in the present case was extremely effective, safe, and straight-forward to operate, resulting in a predictable outcome with little difficulties.

Inadequate width of attached gingiva can lead to difficulty in maintaining oral hygiene, can cause recession and if the patient is undergoing orthodontic treatment the bands and brackets might get engrossed in the buccal mucosa. Therefore, increasing the width of attached gingiva is necessary. Here, authors presents a case of 19-year-old female patient who was referred from the Department of Orthodontics for impinging of bands into gingiva which was identified to be because of in adequate width of attached gingiva. Horizontal incision was given at mucogingival junction from tooth 34 to 44 region. Full-thickness flap was raised till the required vestibular depth recipient site is required. Free Gingival Graft (FGG) of size 15×10 mm in size was harvested from left palatal mucosa from distal to 24 to mesial to 26 region. Harvested FGG was sutured from 32 to 42 region in the recipient site. Platelet Rich Fibrin (PRF) membrane was prepared using patients own blood and this membrane was sutured at 33 and 43 region at the recipient site. An aluminium foil was kept at the donor site and above the membrane at the recipient site on which periodontal pack was given. After 21 days of healing, the width of attached gingiva increased from 2 mm at baseline to 8 mm. According to Visual Analog Scale (VAS), mild pain was felt by the patient and no difference in the colour was seen at both recipient and donor site at 21 days after surgery. Use of FGG and PRF helps to achieve improved results for increase width of attached gingiva.

High-resolution susceptibility weighted imaging (SWI) provides unique contrast to small venous vasculature. The conspicuity of these mesoscopic veins, such as deep medullary veins in white matter, is subject to change from SWI venography when venous oxygenation in these veins is altered due to oxygenated blood susceptibility changes. The changes of visualization in small veins shows potential to depict regional changes of oxygen utilization and/or vascular density changes in the aging brain. The goal of this study was to use WM venous density to quantify small vein visibility in WM and investigate its relationship with neurodegenerative features, white matter hyperintensities (WMHs), and cognitive/functional status in elderly subjects (N = 137). WM venous density was significantly associated with neurodegeneration characterized by brain atrophy (β = 0.046± 0.01, p < 0.001), but no significant association was found between WM venous density and WMHs lesion load (p = 0.3963). Further analysis of clinical features revealed a negative trend of WM venous density with the sum-of-boxes of Clinical Dementia Rating and a significant association with category fluency (1-min animal naming). These results suggest that WM venous density on SWI can be used as a sensitive marker to characterize cerebral oxygen metabolism and different stages of cognitive and functional status in neurodegenerative diseases.

Background: Subjective cognitive decline (SCD), considered a preclinical dementia stage, is less understood in Hispanics, a high-risk group for dementia. We investigated SCD to mild cognitive impairment (MCI) progression risk, as well as baseline and longitudinal features of depressive symptoms, SCD complaints, and objective cognitive performance among Hispanics compared to non-Hispanic Whites (NHW). Methods: Hispanic (n = 23) and NHW (n = 165) SCD participants were evaluated at baseline and 2-year follow-up. Evaluations assessed function, depressive symptoms, SCD, and objective cognitive performance. Results: Hispanics were at increased risk of progression to MCI (OR: 6.10, 95% CI 1.09-34.20, P =.040). Hispanic participants endorsed more depressive symptoms at baseline (P =.048) that worsened more longitudinally (OR: 3.16, 95% CI 1.18-8.51, P =.023). Hispanic participants had increased SCD complaints on the Brief Cognitive Rating Scale (BCRS) (β =.40 SE:.17, P =.023), and in specific BCRS domains: concentration (β =.13, SE:.07, P =.047), past memory (β =.13, SE:.06, P =.039) and functional abilities (β =.10, SE:.05, P =.037). In objective cognitive performance, Hispanic ethnicity associated with decline in MMSE (β = −.27, SE:.13, P =.039), MoCA (β = −.80 SE:.34, P =.032), Trails A (β = 2.75, SE:.89, P =.002), Trails B (β = 9.18, SE: 2.71, P =.001) and Guild Paragraph Recall Delayed (β = −.80 SE:.28, P =.005). Conclusions: Hispanic ethnicity associated with a significantly increased risk of 2-year progression of SCD to MCI compared to NHW. This increased risk associated with increased depressive symptoms, distinctive SCD features, and elevated amnestic and non-amnestic objective cognitive decline. This supports further research to refine the assessment of preclinical dementia in this high-risk group. [ABSTRACT FROM AUTHOR]