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In recent years, contemporary digital dentistry is rapidly evolving as a paradigm shift or revolutionary change in traditional dentistry for delivering high quality of dental care to patients. A significant contribution in the transformation of the dentistry field has been made from the advent of artificial intelligence (AI) and its subsets. Dental traumatic injuries are considered global public health concern. Hence, novel technological advancements, innovations, developments, and high-quality research are needed in the realm of dental traumatology to explore and analyze the various aspects of traumatic dental injuries (TDIs) for ameliorating the dental treatment outcomes. Recently, there have been several studies published pertaining to applications of AI and its subsets (i.e., machine learning and deep learning) in the arenas of dental traumatology. Different facets of TDIs have been delved scientifically using different applications of AI. However, to date, there is no review article published in the available literature in this regard. Therefore, the aim of the current review article was to explore and unveil the findings from the relevant literature pertaining to different applications of AI in the domain of dental traumatology. In this review article, the important findings from the relevant studies have been highlighted in the narrative way. This review would be quite insightful for the dental professionals and researchers in regard to the current status and overview of available literature about the scientific studies and innovative applications of AI in dental traumatology.

Traumatic dental injuries (TDIs) are regarded as public health-related problems or issues due to their higher and variable prevalence and physiological, physical, economic, and psychosocial consequences. In addition, TDIs can have a negative impact on the quality of life of children and adolescents. An appropriate classification or categorization of TDIs is considered to be of significance for diagnosis, its proper dental management and also for the comprehensive recoding, and standard reporting of scientific data of epidemiological studies in the scientific literature. Literature related reveals numerous classifications of TDIs. However, several drawbacks or limitations of the previous classifications and then newer or modified classifications of TDI have been mentioned or reported in relevant literature. Moreover, a wide range of classification systems of TDIs has caused both confusion and contradiction to the understanding in this context. Very recently, International Classification of Disease-11 World Health Organization classification of TDI (2018), Eden Baysal Dental Trauma Index (2020), Modified Eden Baysal Dental Trauma Index (2021), and NA0D (2022) have been reported in the literature. The aim of this article is to overview and highlight the literature related to the different types of classification systems of TDIs.

Endodontics is evolving with modern innovations for conservatively managing the various dental problems involving pulpal or periradicular tissue of primary and permanent teeth. Lasers have been reported with favorable clinical evidence, particularly in tackling the endodontic problems effectively. Recently, the application of lasers in the form of photobiomodulation therapy or low-level laser therapy has been reported in many recent scientific studies/researches with successful results. Hence, this narrative review critically appraise the existing scientific literature and highlights the photobiomodulation technique of lasers as noninvasive therapeutic modality in different pediatric endodontic therapies or procedures (direct pulp capping, pulpotomy, noninvasive treatment of periapical lesion, regenerative endodontics, postendodontic pain management, etc.).

Nonsurgical endodontic therapy is usually advised as primary approach to treat the nonvital teeth with pulpal or periapical infection. However, in certain clinical scenarios and also owing to various factors, surgical modality of endodontics is eventually adopted to manage the recurrent or persistent pulpal or periapical infection and also to treat the failed cases of previously endodontically-treated teeth with conventional approach. In existing literature, there is deficiency of published case report articles regarding successful surgical endodontic management of recurrent pulpal/priapical signs and symptoms and also of failed cases of nonsurgical modality of endodontic therapy in growing pediatric patients. Hence, the present article describes the case report of the effective and successful clinical management of recurrent and failed case of conventional nonsurgical orthograde endodontic therapy by employing the surgical endodontic modality in an adolescent pediatric patient aged 13 years. The whole clinical procedure in step-wise manner has been described, and furthermore, the relevant contemporary endodontic techniques have been elucidated in context of the present case.

Obstructive sleep apnea (OSA) is negatively affecting the health of people and their quality of life. This breathing disorder has a multifactorial etiology. However, orofacial factors in OSA patients have been reported to be relatively more significant factors for its etiopathogenesis and its progression. Polysomnography has been a conventional diagnostic modality for OSA. However, in recent years, various novel and modern detection and diagnostic options have been reported in the current literature. Adenotonsillectomy, positive airway pressure therapy, oral appliances (e.g. mandibular advancement device), and pharmacological drugs (intranasal corticosteroids, etc.) have been known as some of the common treatment modalities for OSA. However, recently several modern therapeutic ways for OSA have been reported in the current literature. The aim of this review article is to comprehensively appraise and highlight the current and recent literature about several aspects of OSA, particularly its modern and novel detection methods and therapeutic options.

Abstract Background Creutzfeldt-Jakob disease (CJD) is a rapidly progressive and ultimately fatal neurodegenerative condition caused by prions. The clinical symptoms of CJD vary with its subtype, and may include dementia, visual hallucinations, myoclonus, ataxia, (extra)pyramidal signs and akinetic mutism. In the early course of disease however, several clinical symptoms of CJD may mimic those of co-existing morbidities. Case presentation We report a male in his 60s with a history of situs inversus totalis and Churg Strauss syndrome, who presented with speech fluency disturbances, neuropsychiatric symptoms and allodynia, a few months after becoming a widower. Initially presumed a bereavement disorder along with a flare-up of Churg Strauss, his symptoms gradually worsened with apraxia, myoclonic jerks and eventually, akinetic mutism. MRI revealed hyperintensities at the caudate nucleus and thalami, while the cerebrospinal fluid was positive for the 14-3-3 protein and the real-time quick test, making the diagnosis of CJD highly probable. This case illustrates the complexities that may arise in diagnosing CJD when pre-existing multimorbidity may cloud the clinical presentation. We also discuss the potential mechanisms underlying the co-occurrence of three rare conditions (situs inversus totalis, Churg Strauss syndrome, CJD) in one patient, taking into consideration the possibility of coincidence as well as common underlying factors. Conclusions The diagnosis of CJD may be easily missed when its clinical symptoms are obscured by those of pre-existing (rare) multimorbidity. This case highlights that when the multimorbidity has neurological manifestations, an extensive evaluation remains crucial to establish the diagnosis, minimize the risk of prion-transmission and provide appropriate guidance to patients and their caregivers.

Background and Aim: Traumatic dental injuries (TDIs) have become the public dental health problem worldwide in children and adolescents. These injuries are complex and multifactorial in aetiology. This study was done with the aim to analyse the association of 'type of TDI' with its demographic and various predisposing factors in children by an advanced statistical method of machine learning (ML) of artificial intelligence (AI). Materials and Methods: The present study's data were gathered by conducting the observational cross-sectional study among index age-groups 12 and 15 years children of randomly selected schools of different geographical regions. Structured interviews and dental examinations performed were done to record the variables of TDIs in self-constructed proforma. The gathered data were analysed by employing the random-tree model of machine learning algorithm of IBM SPSS Modeler version-18 software. Results: Molar-relationship (2.5), age (1.75), sex (1.5) and geographical region/area (~1.5) were the most important predictors (factors) for the determination of type of dental injury as shown by the random tree model, whereas clinical factors like overjet (0.75), lip-competence (0.5) and overbite (0.5) showed lesser importance in the determination of type of TDIs. Conclusion: Demographic factors (age, sex and geographical region) and one clinical factor (molar-relation) were found as the stronger factors for determining the type of traumatic dental injury in children.

Odontogenic cutaneous sinus tract (OCST) of the facial region is rarely found and mostly misdiagnosed because of its variable cutaneous manifestations with the absence of obvious dental symptoms. Usually, patients consider such lesions of dermatologic origin instead of dental origin, and hence, seek its treatment from medical specialists which results in recurrence due to inappropriate treatments without considering the dental etiology, dental history, intra-oral examination, and dental radiographs. The current article presents a case report about chronic OCST at mental region (chin) of the face in a 10-year-old male patient. The source of infection was completely eliminated by endodontic therapy using calcium hydroxide Ca(OH)2 and by conservative surgical debridement of periapical necrotic granulation tissue without excising the extra-oral sinus-tract orifice. The appropriate dental treatment resulted in the resolution of symptoms and rehabilitation of facial esthetics without any recurrence in follow-ups. Thus, the patient's quality of life was improved after successful dental treatment as evaluated by Child's Perception Questionnaire 8–10.

Conservative treatment of the traumatized immature vital permanent teeth is considered critical step for rehabilitating with continued normal development of root and apex closure without adverse sequelae. Hence, the present article describes the case series of successfully and effectively managing the fractured vital immature permanent teeth (Ellis Class-II and Ellis Class-III dental trauma) in pediatric patients by employing three different conservative Vital Pulp Therapy (VPT) approaches using suitable sealing/pulp-capping agents to promote apexogenesis, followed by functional and esthetic restoration. In all the three presented cases, Apexogenesis was achieved without any unfavorable outcome like pulpal or periapical sequelae. Furthermore, the current dental literature relevant to VPT procedures for apexogenesis in young permanent teeth has been thoroughly described in this article.

Nonsurgical endodontic management of the nonvital posterior tooth with large periapical radiolucency has been suggested as conservative approach in endodontics in existing literature. However, complete disinfection of the infected root canals has been a challenge in endodontic procedure. Recently, various types of lasers have emerged as the effective and successful way for achieving in-depth elimination of bacteria and also for healing of periapical lesions. However, there is a scarcity of published case report articles about laser-assisted endodontic therapy in combination with rotary files system for the noninvasive management of large periapical lesion associated with nonvital posterior teeth in claustrophobic child patients. Hence, the aim of this article is to present the pediatric case report about the successful nonsurgical orthograde endodontic treatment by employing diode laser of 810 nm wavelength for the disinfection of the infected root canals and resolution of periradicular radiolucency followed by functional rehabilitation of the treated tooth with preformed stainless steel crown within the shorter period.

Tooth wear (erosion, attrition, or abrasion) has been reported with variable prevalence in children. These clinical entities present a wide range of dental problems and difficulty in dental management in growing children. If tooth wear and its causative/risk factors in primary dentition are not timely addressed, it may negatively affect the permanent teeth later. The current article presents the pediatric case report of successful and effective dental management of a 7-year-old healthy child having dental erosion and attrition with the past history of gastroesophageal reflux disease and Bruxism concurrently in addition to dietary factors (acidic fruits juices and soft-drink). This case presentation has been thoroughly described in a step-wise systematic manner to demonstrate the evidence-based clinical approach for managing such tooth wear problems (combined lesions of erosion and abrasion) in the young pediatric patient by preventive and conservative dental treatment modalities along with appropriate behavior management techniques. Moreover, a review of relevant dental literature about tooth wear and its different clinical aspects has been discussed in this article.

In pediatric dental patients, the management of nonvital immature teeth with undeveloped root in endodontic practice pose difficult and cumbersome clinical situations or challenges for the dental practitioners owing to the various factors, namely, the shorter root with thinner dentinal walls and the lack of apical closure make the affected tooth difficult to obturate conventionally and also make more vulnerable to root fracture. Conventionally, apexification and later apical barrier/plug endodontic modalities have been widely undertaken for such affected teeth. However, such treatment approaches have several intrinsic shortcomings such as uncertain long-term treated tooth prognosis. Since recent years, a biologically based therapeutic endodontic approach known as regenerative endodontic therapy has been or being extensively explored or studied to overcome the drawbacks of previous conventional treatment modalities and also to improve the long-term prognosis of the affected immature nonvital teeth in children and adolescents. Regenerative endodontics is a rapidly evolving subject and also a promising treatment modality for the scientific researchers and clinicians, respectively. Hence, the present article aims to comprehensively and critically appraise the recent literature pertaining to regenerative endodontic procedures. The relevant literature regarding the regenerative endodontics was searched in electronic databases. The articles were retrieved using Boolean operators with relevant keywords/Medical Subject Headings. The included relevant articles were critically appraised in the present review. The latest important aspects of regenerative endodontic have been described in a systematic manner for its better understanding and deeper insights for the general and pediatric dental professionals.

Objective: This research is primarily conducted to determine the psychometric properties of the Beliefs about Emotions Scale (BES) in community and clinical samples. The BES is a scale measure used for evaluating individuals’ beliefs in terms of how acceptable it is for them to experience and express their emotions. Method: This study was conducted on two separate samples. In the first part, 300 individuals were selected from a general sample in Tehran using the quota sampling method. For the second part of the study, we used purposive sampling to gather data from 119 patients suffering from Major Depressive Disorder (MDD) and 121 patients from Somatic Symptoms Disorder (SSD), whose disorders were diagnosed based on the DSM-5 diagnostic criteria. The BES structural validity was examined through Confirmatory Factor Analysis (CFA). Additionally, test-retest composite and internal consistency indices were explored to investigate the reliability of the BES score. Finally, the associations of the BES score with the Hospital Anxiety and Depression Scale (HADS), Young Schema Questionnaire (YSQ), Multidimensional Perfectionism Scale (MPS), Difficulties in Emotion Regulation Scale (DERS), and Emotion Regulation Questionnaire (ERQ) scores were highlighted to investigate the discriminant and convergent validity of the BES score. Results: According to CFAs, the one-factor model for the BES demonstrated a good fit with the data collected from both the clinical and community samples. The internal consistency (Cronbach's alpha) was satisfactory in the community sample (α = 0.84) and the clinical samples of SSD (α = 0.86) and MDD (α = 0.83). The community sample demonstrated high overall test-retest reliability (ICC = 0.93, P < 0.001; 95% CI: 0.89 - 0.95). In terms of convergent validity, the findings confirmed that in the MMD sample, there was a significant relationship between the BES and almost all measures (including Depression (r = 0.39, P < 0.01), Anxiety (r = 0.21, P < 0.05), Self-Sacrifice (r = 0.27, P < 0.01), MPS-total score (r = 0.22, P < 0.05), DERS total score (r = 0.50, P < 0.01), and Suppression (r = 0.38, P < 0.01). However, in the SSD group, this finding was not found. Conclusion: The results demonstrated that the Persian BES is a reliable and valid scale of maladaptive beliefs about emotions which could be implemented for both clinical and research aims.

Abstract Tumor phenotype is shaped both by transforming genomic alterations and the normal cell-of-origin. We identified a cell-of-origin associated prognostic gene expression signature, ET-9, that correlates with remarkably shorter overall and relapse free breast cancer survival, 8.7 and 6.2 years respectively. The genes associated with the ET-9 signature are regulated by histone deacetylase 7 (HDAC7) partly through ZNF92, a previously unexplored transcription factor with a single PubMed citation since its cloning in 1990s. Remarkably, ZNF92 is distinctively over-expressed in breast cancer compared to other tumor types, on a par with the breast cancer specificity of the estrogen receptor. Importantly, ET-9 signature appears to be independent of proliferation, and correlates with outcome in lymph-node positive, HER2+, post-chemotherapy and triple-negative breast cancers. These features distinguish ET-9 from existing breast cancer prognostic signatures that are generally related to proliferation and correlate with outcome in lymph-node negative, ER-positive, HER2-negative breast cancers. Our results suggest that ET-9 could be also utilized as a predictive signature to select patients for HDAC inhibitor treatment.

Background: Luxation dental injuries are considered a severe form of traumatic dental injury (TDI) due to several factors. International association of dental traumatology (IADT) has suggested various treatment approaches for suitable clinical conditions of the injured tooth and other factors. Case Report: The current article presents a case report of the successful and effective clinical management of luxated permanent incisors in an adolescent patient’s traumatic occlusion (dental trauma-induced crossbite relation) by employing single-arch fixed orthodontic therapy with light forces using Nickel-Titanium (NiTi) archwire. Conclusion: Lateral luxation injuries with traumatic occlusion (locked position of involved teeth) can be effectively repositioned by orthodontic traction using light orthodontic forces of NiTi archwire, particularly in patients who seek dental treatment after a few days of a TDI event.

Introduction: Traumatic dental injuries (TDIs) are the public dental health concern, with variable prevalence reported worldwide. Although, TDI is not a disease rather, it is a result of various risk factors. This study was performed to assess the influence of anatomical risk factors such as accentuated overjet, overbite, molar relationship, and lip competency in determining the number of traumatized teeth per affected individual by using the advanced statistical method of multilayer perceptron (MLP) model of deep learning algorithm of artificial intelligence (AI). Materials and Methods: A cross-sectional study consisted of 1000 school children (boys and girls) of index age groups between 12 and 15 years selected through multistage sampling technique. Orofacial anatomical risk factors associated with TDI were statistically analyzed by MLP model of deep learning algorithm of AI using IBM SPSS Modeler software (version 18, 2020). Results: MLP method revealed results in terms of normalized importance as overbite (100%) was the strongest risk factor for the occurrence of TDI in number of teeth of affected participants, followed by molar relationship (90.2%), overjet (87.7%), and the lip competency was found as the weakest risk factor. Conclusion: Using the MLP as statistical method, overbite was found as the strongest anatomical risk factor in determining the number of traumatized teeth per affected individual as compared to molar relationship, overjet, and lip competence.

The molecular topology and the chemical structures which are not regular perform a dominant character in designing the compound in connection with their physical and chemical properties. The study of topological descriptors of molecular structures is widely used in the field of cheminformatics, information technology, biomedical science, and many more. Numerous topological indices have been evolved in the theory of chemistry. Graphs which are not regular can be specified using irregular measures. In this article, we find some irregularity indices, which are useful in Quantitative structure activity relationship for benzenoid structures. Based on the exact analytic expressions, the numerical and graphical comparison for benzenoid structures is also provided.

Objective: To determine the frequency and association of depression among caregivers of psychiatric patients. Study Design: Cross-sectional study. Study place and duration: Outpatient Department of a Tertiary Care Hospital, Rawalpindi, from Sep 2016 to Apr 2017. Methodology: A total of 200 caregivers of psychiatric patients were included in this study. Each caregiver was interviewed by a consultant psychiatrist to measure the frequency of depression according to International Classification of Disease-10 (ICD10) criteria and Hospital Anxiety and Depression Scale (HADS) score of >8. Socio-demographic factors were associated with presence of depression by using chi-square test. Results: The mean age observed was 35.36 ± 8.39 years. There were 84 (42%) males and 116 (58%) females. Depression was found in 95 (47.5%) caregivers of psychiatric patients in our analysis. Female gender, low socio-economic status and type of psychiatric illness had significant relationship with presence of depression among our target population. Conclusion: Depression was a highly common undiagnosed entity among the caregivers of psychiatric patients. Female caregivers or caregivers with low socio-economic status should be screened especially for depression in addition to caregivers of patients suffering from psychotic illness.

Mast cells are critical effectors of allergic inflammation and protection against parasitic infections. Here the authors demonstrate that GATA2 promotes chromatin accessibility at the super-enhancers of mast cell identity genes and primes both typical and super-enhancers at genes that respond to antigenic stimulation.

SUMMARY During the laparoscopic cholecystectomy, a rare variation was found in a female patient. There was a large vessel exiting from liver parenchyma to gall bladder directly. It was pulsating; so was an unusual artery. The cystic artery was present properly at its usual anatomical site in Callot's triangle. The knowledge of these vascular variations is very significant in surgical interventions involving the biliary tree. It is of key importance for laparoscopic surgeons to know like this vascular variation to avoid catastrophic bleeding. The report emphasizes the vascular variation and the anomalous vessel to accomplish safe and uneventful hepatobiliary surgeri

BACKGROUND: Traumatic dental injuries (TDIs) are becoming a worldwide phenomenon owing to their variable prevalence, and their etiology is considered multifactorial and complex in interactions among various risk factors. These are preventable if risk factors are analyzed and interpreted in all possible scientific manners. The objective of this study was to assess the various environmental risk factors (places of occurrence of TDI) among World Health Organization (WHO) index-aged children and adolescents (12 and 15 years). MATERIAL AND METHODS: This was the epidemiological cross-sectional study conducted in Aligarh City, Uttar Pradesh, India, in the year 2018, with a sample size of 1000. Multistage random sampling technique was employed. Study data were collected by doing dental examination and structured interview with self-prepared pro forma in ten randomly selected sampling sites (schools) from different regions of the city. Subsequently, data were entered in an Excel sheet and then analyzed with the Chi-square test using the Statistical Package for the Social Sciences (SPSS) software. RESULTS: Overall, school (63; 46.7%) was found to be the most prevalent environmental risk factor for TDI followed by home (37; 27.4%), roadside (10; 7.4%), and playground (9; 6.7%). Fifteen (11.1%) affected individuals were not able to recall the place of the TDI incident, while 0.7% (1) had TDI occurrence in other places. Among 12-year index-aged children, home (15; 34.1%) was the most common place of TDI in rural regions, while school (27; 67.5%) was the most frequent place of TDI in urban regions. Among 15-year index-aged adolescents, school (19; 59.4%) was found to be the most common place in rural regions, whereas school (9; 47.4%) was the most frequent place of TDI in urban regions. CONCLUSION: Environmental factors, especially school premises, infrastructure, and playing facilities, need to be upgraded and built with an emphasis on a safer environment for children. Teachers, parents, and school children should be educated and made aware of the preventive measures for dental injuries in schools and homes. Appropriate safety gears should be mandatory to use among children and adolescents during outdoor sports and recreational activities.

Abstract Background Medication safety in cancer patients receiving complex medication regimens is an important problem in various settings. Medication related events, interceptions and interventions are not well described in this area. We intended to study incidence, types, settings and stages involved, root cause analysis, medication classes involved and the level of harm cause by medication errors in two hospitals providing oncology services comparatively. The severity of incidents and interventions are studied. Methods It was a prospective cross sectional study among cancer in-patients of two tertiary care hospitals of KPK. Scale by NCC-MERP was used for evaluation of all medication related incidents. The data obtained was analyzed by IBM SPSS statistics 22 with 95% confidence interval and used the same for other descriptive statistics. Results All medication orders were reviewed at both sites (Computerized Prescription Order Entry and HWP systems). Potential ADEs incidence was found high at site 2 (97.5%) while medication errors without harm was high at site 1 (97.5%). Most events occur at prescribing level 87.6 and 81.7% at both sites 1 and 2. Types highly reported involved improper dose 31.4 and 15.5%, monitoring error 14.6 and 15.2% at site 1 and 2. Medications involved in these incidents were antibiotics 44 and 12.7%, antiemetic 7.5 and 15.8% and antineoplastic 2.9 and 9.4% at site 1 and 2. Severity of 3.6 and 36.5% incidents had potential to cause harm at site 1 and 2. Root causes were human factors 62.6 and 72.3%, drug selection 33.6 and 38.8%, and dose selection 39.6 and 15.3% at sites 1 and 2. Contributing factors including staff training 33.6 and 24.3%, system for covering patient care 14.9 and 36.6%, communication system 2.4 and 20.3%, interruptions 9.7 and 7.3% and others 78.8 and 68.6% were highly reported. Preventability of medication errors was 99% at both sites. Intervention was taken in 90.5% events at site 1 (CPOE system) while the incidence lowest at site 2 (HWP system). Conclusion Medication related events are high among cancer in-patients at the site lacking updated electronic system for medication prescribing. Proper training about medication safety, reporting and interventions are required.

Cell cycle is a cellular process that is subject to stringent control. In contrast to the wealth of knowledge of proteins controlling the cell cycle, very little is known about the molecular role of lncRNAs (long noncoding RNAs) in cell-cycle progression. By performing genome-wide transcriptome analyses in cell-cycle-synchronized cells, we observed cell-cycle phase-specific induction of >2000 lncRNAs. Further, we demonstrate that an S-phase-upregulated lncRNA, SUNO1, facilitates cell-cycle progression by promoting YAP1-mediated gene expression. SUNO1 facilitates the cell-cycle-specific transcription of WTIP, a positive regulator of YAP1, by promoting the co-activator, DDX5-mediated stabilization of RNA polymerase II on chromatin. Finally, elevated SUNO1 levels are associated with poor cancer prognosis and tumorigenicity, implying its pro-survival role. Thus, we demonstrate the role of a S-phase up-regulated lncRNA in cell-cycle progression via modulating the expression of genes controlling cell proliferation.

Introduction: Many genetic studies are conducted on Obsessive-Compulsive Disorder (OCD). however, a high-throughput examination of proteome profile of this severe disease has not been performed yet. Methods: Here, the proteomic study of OCD patients serum samples was conducted by the application of Two-Dimensional Electrophoresis (2DE) followed by Mass Spectrometry (MALDI-TOF-TOF). Results: A total of 240 protein spots were detected and among them, five significant differentially expressed protein spots with the fold change of ≥1.5 were considered for further evaluations. These proteins include IGKC, GC, HPX, and two isoforms of HP. While IGKC and HP show down-regulation, GC and HPX indicate up-regulation. Moreover, a validation study of overall HP levels in patients serum via nephelometric quantification confirmed the lower levels of this protein in the serum of OCD patients. Additionally, enrichment analysis and validation test revealed that inflammation is one of most dominant processes in OCD. Conclusion: It is suggested that these candidate proteins and their underlying processes (especially, inflammation) may be linked to OCD pathophysiology and can promise a clinical use after extensive validation studies.

Abstract Background Mixed vascular and neurodegenerative dementia, such as Alzheimer’s disease (AD) with concomitant cerebrovascular disease, has emerged as the leading cause of age-related cognitive impairment. The brain white matter (WM) microstructural changes in neurodegeneration well-documented by diffusion tensor imaging (DTI) can originate from brain tissue or extracellular free water changes. The differential microstructural and free water changes in AD with and without cerebrovascular disease, especially in normal-appearing WM, remain largely unknown. To cover these gaps, we aimed to characterize the WM free water and tissue microstructural changes in AD and mixed dementia as well as their associations with cognition using a novel free water imaging method. Methods We compared WM free water and free water-corrected DTI measures as well as white matter hyperintensity (WMH) in patients with AD with and without cerebrovascular disease, patients with vascular dementia, and age-matched healthy control subjects. Results The cerebrovascular disease groups had higher free water than the non-cerebrovascular disease groups. Importantly, besides the cerebrovascular disease groups, patients with AD without cerebrovascular disease also had increased free water in normal-appearing WM compared with healthy control subjects, reflecting mild vascular damage. Such free water increases in WM or normal-appearing WM (but not WMH) contributed to dementia severity. Whole-brain voxel-wise analysis revealed a close association between widespread free water increases and poorer attention, executive functioning, visual construction, and motor performance, whereas only left hemispheric free water increases were related to language deficits. Moreover, compared with the original DTI metrics, the free water-corrected DTI metric revealed tissue damage-specific (frontal and occipital) microstructural differences between the cerebrovascular disease and non-cerebrovascular disease groups. In contrast to both lobar and subcortical/brainstem free water increases, only focal lobar microstructural damage was associated with poorer cognitive performance. Conclusions Our findings suggest that free water analysis isolates probable mild vascular damage from WM microstructural alterations and underscore the importance of normal-appearing WM changes underlying cognitive and functional impairment in AD with and without cerebrovascular disease. Further developed, the combined free water and tissue neuroimaging assays could help in differential diagnosis, treatment planning, and disease monitoring of patients with mixed dementia.

We present a rare case of PL-7 antisynthetase syndrome (ASS) in association with Sjögren’s, systemic lupus erythematosus (SLE), and seropositive rheumatoid arthritis (RA). Initially, the patient was diagnosed with Sjögren’s followed by Sjögren’s/SLE overlap and then Sjögren’s/SLE/RA overlap. She was eventually diagnosed with Sjögren’s/SLE/RA overlap with PL-7 ASS with interstitial lung disease (ILD). ILD was discovered after complaints of pleuritic chest pain with subsequent workup with coronary computed tomography (CT) revealing pulmonary fibrosis. This case demonstrates the ambiguity with which symptoms of ASS can present; given the high respiratory morbidity and mortality of ASS especially in non-Jo-1 patients, those who present with Raynaud’s, myositis, or joint pain, whether together or in isolation, should be assessed for presence of additional features of ASS and potentially undergo testing for ASS antibodies if appropriate.

Objective: To assess the relation between a sum score of imaging markers indicative of cerebral amyloid angiopathy (CAA) and cognitive impairment, stroke, dementia, and mortality in a general population.Methods: One thousand six hundred twenty-two stroke-free and dementia-free participants of the population-based Rotterdam Study (mean age 73.1 years, 54.3% women) underwent brain MRI (1.5 tesla) in 2005–2011 and were followed for stroke, dementia and death until 2016–2017. Four MRI markers (strictly lobar cerebral microbleeds, cortical superficial siderosis, centrum semiovale perivascular spaces, and white matter hyperintensities) were combined to construct the CAA sum score, ranging from 0 to 4. Neuropsychological testing measured during the research visit closest to scan date were used to assess general cognitive function and cognitive domains. The associations of the CAA sum score with cognition cross-sectionally and with stroke, dementia, and mortality longitudinally were determined using linear regression and Cox proportional hazard modeling adjusted for age, sex, hypertension, cholesterol, lipid lowering medication, atrial fibrillation, antithrombotic medication and APOE-ε2/ε4 carriership. Additionally, we accounted for competing risks of death due to other causes for stroke and dementia, and calculated absolute risk estimates.Results: During a mean follow-up of 7.2 years, 62 participants suffered a stroke, 77 developed dementia and 298 died. Participants with a CAA score of 1 showed a lower Mini-Mental-State-Exam (fully-adjusted mean difference −0.21, 95% CI (−0.42–0.00) compared to a score of 0. In general, for increased CAA scores we saw a lower g-factor. The age and sex-adjusted hazard ratios (HRs) per point increase of the CAA score were 1.41 for stroke (95% CI, 0.99–2.00), 1.19 for dementia (95% CI, 0.86–1.65), and 1.26 for mortality (95% CI, 1.07–1.48). The results for dementia and stroke risk did not differ after correcting for the competing risk of death. For all outcomes, higher CAA scores showed higher absolute risk estimates over 10 years.Conclusions: Our results suggest that in this community-dwelling population, a higher CAA score is related to cognitive impairment and a higher risk of stroke, dementia, and death. The composite CAA score can be used to practically quantify the severity of vascular brain injury.

Objective To explore the additive effect of neurodegenerative diseases, measured by atrophy, on neurocognitive function in Asian dementia-free elderly with cerebrovascular disease (CeVD).Methods The present study employed a cross-sectional design and was conducted between 2010 and 2015 among community-dwelling elderly participants recruited into the study. Eligible participants were evaluated with an extensive neuropsychological battery and neuroimaging. The weighted CeVD burden scale comprising markers of both small- and large-vessel diseases was applied, with a score of ≥2, indicating significant CeVD burden. Cortical atrophy (CA) and medial temporal atrophy (MTA) were graded using the global cortical atrophy scale and Schelten’s scale, respectively. Global and domain-specific (attention, executive function, language, visuomotor speed, visuoconstruction, visual memory, and verbal memory) neurocognitive performance was measured using a locally validated neuropsychological battery (Vascular Dementia Battery, VDB).Results A total of 819 dementia-free participants were included in the analysis. Among none-mild CeVD subjects, there was no significant difference in the global cognitive performance across atrophy groups (no atrophy, CA, and CA+MTA). However, in moderate-severe CeVD subjects, CA+MTA showed significantly worse global cognitive performance compared with those with CA alone (mean difference=−0.35, 95% CI −0.60 to −0.11, p=0.002) and those without atrophy (mean difference=−0.46, 95% CI −0.74 to −0.19, p

Panax ginseng has been used as a traditional medicine to strengthen human health for centuries. Over the last decade, significant agronomical progress has been made in the development of elite ginseng cultivars, increasing their production and quality. However, as one of the significant environmental factors, heat stress remains a challenge and poses a significant threat to ginseng plants’ growth and sustainable production. This study was conducted to investigate the phenotype of ginseng leaves under heat stress using hyperspectral imaging (HSI). A visible/near-infrared (Vis/NIR) and short-wave infrared (SWIR) HSI system were used to acquire hyperspectral images for normal and heat stress-exposed plants, showing their susceptibility (Chunpoong) and resistibility (Sunmyoung and Sunil). The acquired hyperspectral images were analyzed using the partial least squares-discriminant analysis (PLS-DA) technique, combining the variable importance in projection and successive projection algorithm methods. The correlation of each group was verified using linear discriminant analysis. The developed models showed 12 bands over 79.2% accuracy in Vis/NIR and 18 bands with over 98.9% accuracy at SWIR in validation data. The constructed beta-coefficient allowed the observation of the key wavebands and peaks linked to the chlorophyll, nitrogen, fatty acid, sugar and protein content regions, which differentiated normal and stressed plants. This result shows that the HSI with the PLS-DA technique significantly differentiated between the heat-stressed susceptibility and resistibility of ginseng plants with high accuracy.

Aims: To examine the diagnostic utility of the National Institute of Neurological Disorders and Stroke and the Canadian Stroke Network (NINDS-CSN) neuropsychological battery in memory clinics comparing controls with patients with no cognitive impairment (NCI), patients with cognitive impairment-no dementia (CIND) at varying severity levels (mild/moderate), and patients with dementia. Methods: A total of 405 participants with NCI, CIND or dementia were assessed with the NINDS-CSN battery. The discriminatory properties of all three protocols (5, 30 and 60 min) before and after education stratification (none/primary vs. secondary/above) were examined by receiver operating characteristic curves. Results: Overall, the shorter protocols are equivalent to the longer protocol in diagnosing dementia, regardless of education. To discriminate between nondementia groups, before education stratification, the 5-min protocol showed varied discriminatory properties between different diagnostic/severity groups. After stratification, the 5-min protocol was broadly equivalent to the longer protocols in lower-education groups [area under the curve (AUC) range: 0.77-0.87] but was less accurate in the higher-education groups (AUC range: 0.68-0.78). The 30- and 60-min protocol constantly showed moderate-to-excellent differentiating capacities regardless of education (AUC range: 0.80-0.90). Conclusion: The NINDS-CSN neuropsychological battery can be applied in memory clinics and effectively discriminate between cognitively intact individuals and those with cognitive impairments of varying severity. Furthermore, level of education should be taken into consideration when choosing protocols with different lengths for cognitive assessment.

According to the network-based neurodegeneration hypothesis, neurodegenerative diseases target specific large-scale neural networks, such as the default mode network, and may propagate along the structural and functional connections within and between these brain networks. Cognitive impairment no dementia (CIND) represents an early prodromal stage but few studies have examined brain topological changes within and between brain structural and functional networks. To this end, we studied the structural networks [diffusion magnetic resonance imaging (MRI)] and functional networks (task-free functional MRI) in CIND (61 mild, 56 moderate) and healthy older adults (97 controls). Structurally, compared with controls, moderate CIND had lower global efficiency, and lower nodal centrality and nodal efficiency in the thalamus, somatomotor network, and higher-order cognitive networks. Mild CIND only had higher nodal degree centrality in dorsal parietal regions. Functional differences were more subtle, with both CIND groups showing lower nodal centrality and efficiency in temporal and somatomotor regions. Importantly, CIND generally had higher structural-functional connectome correlation than controls. The higher structural-functional topological similarity was undesirable as higher correlation was associated with poorer verbal memory, executive function, and visuoconstruction. Our findings highlighted the distinct and progressive changes in brain structural-functional networks at the prodromal stage of neurodegenerative diseases.

This study explores whether the Mini-Mental State Examination (MMSE) could reliably exclude definite dementia and dementia-free cases from requiring more extensive neuropsychological investigations in memory clinic settings in Singapore. Patients with memory complaints referred for possible dementia underwent the MMSE, followed by standardized neuropsychological and clinical assessments which led to a consensus diagnosis. MMSE cut-off points were derived stratified for education (less and equal/above primary level). Results show that after education stratification, using an optimal Positive Likelihood Ratio (PLR) and optimal Negative Likelihood Ratio (NLR), a higher percentage of patients were correctly identified as having dementia or dementia-free, with minimal misclassification rate. The finding suggests the MMSE can be used to exclude patients not requiring full neuropsychological assessments in a memory clinic.

Background: Retinal microvascular network changes have been found in patients with age-related brain diseases such as stroke and dementia including Alzheimer's disease. We examine whether retinal microvascular network changes are also present in preclinical stages of dementia. Methods: This is a cross-sectional study of 300 Chinese participants (age: ≥60 years) from the ongoing Epidemiology of Dementia in Singapore study who underwent detailed clinical examinations including retinal photography, brain imaging and neuropsychological testing. Retinal vascular parameters were assessed from optic disc-centered photographs using a semiautomated program. A comprehensive neuropsychological battery was administered, and cognitive function was summarized as composite and domain-specific Z-scores. Cognitive impairment no dementia (CIND) and dementia were diagnosed according to standard diagnostic criteria. Results: Among 268 eligible nondemented participants, 78 subjects were categorized as CIND-mild and 69 as CIND-moderate. In multivariable adjusted models, reduced retinal arteriolar and venular fractal dimensions were associated with an increased risk of CIND-mild and CIND-moderate. Reduced fractal dimensions were associated with poorer cognitive performance globally and in the specific domains of verbal memory, visuoconstruction and visuomotor speed. Conclusion: A sparser retinal microvascular network, represented by reduced arteriolar and venular fractal dimensions, was associated with cognitive impairment, suggesting that early microvascular damage may be present in preclinical stages of dementia.

Objective: There is evidence for differential executive function in Bipolar I Disorder (BID) and schizophrenia that may tend different cognitive deficits and abnormalities. The objective of this sudsy was to compare the executive function of BID and schizophrenic patients. Materials & Methods: We studied 50 patients with BID, and 50 with schizophrenia participants in outpatients' clinic of Rouzbeh hospital. All participants completed the Wisconsin Card Sorting Test (WCST) the Persian version. The participants were mach in three basic variables which had most contributions in cognitive conditions in patients. They were Age, educational status and period of illness. Results: The two patient groups had compared performance on the WCST in compared with general population (P

The terms “mal(e)development” and “(com)modification” are coinages that underscore the nexus of the patriarchy, colonialism and capitalism in the Indian context. India has witnessed tremendous development and exploitation of its natural resources in the post‑independence era owing to the aids sponsored by the developed nations. The mal(e) development and (com)modification of India on the western model is masquerading as nation building in the 21st century. Arundhati Roy, the prominent feminist writer‑activist, lays bare this camouflaged maldevelopment and commodification of nature and women. Roy’s concerns are pretty much influenced by eco‑feministic discourse. In post‑independence India, colonialism has resorted to subterfuge, presenting a Western model of development to the developing nations.

Studies on the impact of small vessel disease (SVD) on cognition generally focus on white matter hyperintensity (WMH) volume. The extent to which WMH location relates to cognitive performance has received less attention, but is likely to be functionally important. We examined the relation between WMH location and cognition in a memory clinic cohort of patients with sporadic SVD.A total of 167 patients with SVD were recruited from memory clinics. Assumption-free region of interest-based analyses based on major white matter tracts and voxel-wise analyses were used to determine the association between WMH location and executive functioning, visuomotor speed and memory.Region of interest-based analyses showed that WMHs located particularly within the anterior thalamic radiation and forceps minor were inversely associated with both executive functioning and visuomotor speed, independent of total WMH volume. Memory was significantly associated with WMH volume in the forceps minor, independent of total WMH volume. An independent assumption-free voxel-wise analysis identified strategic voxels in these same tracts. Region of interest-based analyses showed that WMH volume within the anterior thalamic radiation explained 6.8% of variance in executive functioning, compared to 3.9% for total WMH volume; WMH volume within the forceps minor explained 4.6% of variance in visuomotor speed and 4.2% of variance in memory, compared to 1.8% and 1.3% respectively for total WMH volume.Our findings identify the anterior thalamic radiation and forceps minor as strategic white matter tracts in which WMHs are most strongly associated with cognitive impairment in memory clinic patients with SVD. WMH volumes in individual tracts explained more variance in cognition than total WMH burden, emphasizing the importance of lesion location when addressing the functional consequences of WMHs.

Purpose. To assess the repeatability of spectral-domain optical coherence tomography to measure macular and perimacular ganglion cell complex thicknesses and compare retinal ganglion cell parameters between algorithms. Methods. Ninety-two nonglaucomatous eyes from 92 participants underwent macular and perimacular ganglion cell complex thickness measurement using OCT-HS100 Glaucoma 3D algorithm and these measurements were repeated for 34 subjects. All subjects also had macular ganglion cell-inner plexiform layer thickness measured by Cirrus HD-OCT Ganglion Cell Analysis algorithm. Intraclass correlation coefficient and Pearson’s correlation analyses were performed. Results. Subfields of both macular and perimacular ganglion cell complex thicknesses had high intraclass correlation coefficient values between 0.979 (95% confidence interval [CI]: 0.958–0.989) and 0.981 (95% CI: 0.963, 0.991) and between 0.70 (95% CI: 0.481–0.838) and 0.987 (95% CI: 0.956–0.989), respectively. The overall average ganglion cell complex and macular average ganglion cell-inner plexiform layer thicknesses were strongly correlated (r=0.83, P

Purpose. We examined the association of CKD defined by serum creatinine, serum cystatin C, and albuminuria with moderate diabetic retinopathy (DR). Methods. We examined 1,119 Indian adults with diabetes, aged 40–80 years, who participated in the Singapore Indian Eye Study (2007–2009), a population-based cross-sectional study. The associations of CKD defined by each of the three markers alone and in combination with moderate DR were examined using logistic regression models adjusted for potential confounding factors including duration of diabetes, smoking, body mass index, systolic blood pressure, and HbA1c. Results. The prevalence of moderate DR was significantly higher among those with CKD defined by triple markers (41.1%) compared to CKD defined separately by creatinine (26.6%), cystatin C (20.9%), and albuminuria (23.4%). People with CKD defined by triple markers had a fourteenfold higher odds of moderate DR (OR (95% CI) = 13.63 (6.08–30.54)) compared to those without CKD by any marker. Nearly half (48.7%) of participants with cystatin C ≥ 1.12 mg/L have moderate DR. Conclusions. CKD defined by a triple marker panel was strongly associated with moderate DR in this Asian population with diabetes.

Alzheimer's Disease (AD) is the most common subtype of dementia. As the prevalence of dementia is projected to increase, the burden of the disease on society is expected to become increasingly significant. The link between eye pathology and neurodegenerative diseases has been established in multiple studies. In particular, optic nerve parameters associated with neuronal loss in AD include retinal ganglion cells (RGC). Retinal ganglion cells are similar to neurons in the cerebral cortex, and have been correlated to neurodegeneration in AD. Ocular imaging techniques such as optical coherence tomography (OCT) have provided a rapid and non-invasive method for quantifying optic nerve parameters in vivo . Spectral domain (SD)-OCT has shown good potential in the study of the optic nerve in AD as it enables more comprehensive assessment of RGCs. Earlier generation OCT techniques only assess the retinal nerve fibre layer, which consists of RGC axons. Spectral domain-OCT offers ultra-high scan speed and image resolution, enabling improved sampling of retinal layers. Retinal layers such as the ganglion cell-inner plexiform layer (GC-IPL), which contain the dendrites and nuclei of RGCs, can be assessed with SD-OCT. This article presents a review of literature associating eye pathology with AD, and explores the potential of SD-OCT in future AD studies. Spectral domain-OCT has the potential to draw more links between optic nerve pathology and neurodegeneration.

C-reactive protein (CRP) levels are associated with cardiovascular disease and systemic inflammation. We assessed whether CRP-associated loci were associated with serum CRP and retinal markers of microvascular disease, in Asian populations.Genome-wide association analysis (GWAS) for serum CRP was performed in East-Asian Chinese (N = 2,434) and Malays (N = 2,542) and South-Asian Indians (N = 2,538) from Singapore. Leveraging on GWAS data, we assessed, in silico, association levels among the Singaporean datasets for 22 recently identified CRP-associated loci. At loci where directional inconsistencies were observed, quantification of inter-ethnic linkage disequilibrium (LD) difference was determined. Next, we assessed association for a variant at CRP and retinal vessel traits [central retinal artery equivalent (CRAE) and central retinal vein equivalent (CRVE)] in a total of 24,132 subjects of East-Asian, South-Asian and European ancestry.Serum CRP was associated with SNPs in/near APOE, CRP, HNF1A and LEPR (p-values ≤4.7×10(-8)) after meta-analysis of Singaporean populations. Using a candidate-SNP approach, we further replicated SNPs at 4 additional loci that had been recently identified to be associated with serum CRP (IL6R, GCKR, IL6 and IL1F10) (p-values ≤0.009), in the Singaporean datasets. SNPs from these 8 loci explained 4.05% of variance in serum CRP. Two SNPs (rs2847281 and rs6901250) were detected to be significant (p-value ≤0.036) but with opposite effect directions in the Singaporean populations as compared to original European studies. At these loci we did not detect significant inter-population LD differences. We further did not observe a significant association between CRP variant and CRVE or CRAE levels after meta-analysis of all Singaporean and European datasets (p-value >0.058).Common variants associated with serum CRP, first detected in primarily European studies, are also associated with CRP levels in East-Asian and South-Asian populations. We did not find a causal link between CRP and retinal measures of microvascular disease.

BackgroundOverweight and obesity are thought to significantly influence a person's risk of cardiovascular disease, possibly via its effect on the microvasculature. Retinal vascular caliber is a surrogate marker of microvascular disease and a predictor of cardiovascular events. The aim of this systematic review and meta-analysis was to determine the association between body mass index (BMI) and retinal vascular caliber.Methods and findingsRelevant studies were identified by searches of the MEDLINE and EMBASE databases from 1966 to August 2011. Standardized forms were used for data extraction. Among over 44,000 individuals, obese subjects had narrower arteriolar and wider venular calibers when compared with normal weight subjects, independent of conventional cardiovascular risk factors. In adults, a 1 kg/m(2) increase in BMI was associated with a difference of 0.07 μm [95% CI: -0.08; -0.06] in arteriolar caliber and 0.22 μm [95% CI: 0.21; 0.23] in venular caliber. Similar results were found for children.ConclusionsHigher BMI is associated with narrower retinal arteriolar and wider venular calibers. Further prospective studies are needed to examine whether a causative relationship between BMI and retinal microcirculation exists.

Corneal astigmatism refers to refractive abnormalities and irregularities in the curvature of the cornea, and this interferes with light being accurately focused at a single point in the eye. This ametropic condition is highly prevalent, influences visual acuity, and is a highly heritable trait. There is currently a paucity of research in the genetic etiology of corneal astigmatism. Here we report the results from five genome-wide association studies of corneal astigmatism across three Asian populations, with an initial discovery set of 4,254 Chinese and Malay individuals consisting of 2,249 cases and 2,005 controls. Replication was obtained from three surveys comprising of 2,139 Indians, an additional 929 Chinese children, and an independent 397 Chinese family trios. Variants in PDGFRA on chromosome 4q12 (lead SNP: rs7677751, allelic odds ratio = 1.26 (95% CI: 1.16-1.36), P(meta) = 7.87×10(-9)) were identified to be significantly associated with corneal astigmatism, exhibiting consistent effect sizes across all five cohorts. This highlights the potential role of variants in PDGFRA in the genetic etiology of corneal astigmatism across diverse Asian populations.

This corrects the article DOI: 10.1038/sdata.2017.179.