ObjectivesTo assess the prevalence and factors associated with mild cognitive impairment (MCI) among older adults in an urban area of South India.SettingThe study was conducted in the capital city of ...Thiruvananthapuram in the South Indian state of Kerala.ParticipantsThe study participants were community-dwelling individuals aged 60 years and above.Primary outcome measureMCI was the primary outcome measure and was defined using the criteria by European Alzheimer’s Disease Consortium. Cognitive assessment was done using the Malayalam version of Addenbrooke’s Cognitive Examination tool. Data were also collected on sociodemographic variables, self-reported comorbidities like hypertension and diabetes, lifestyle factors, depression, anxiety and activities of daily living.ResultsThe prevalence of MCI was found to be 26.06% (95% CI of 22.12 to 30.43). History of imbalance on walking (adjusted OR 2.75; 95 % CI of 1.46 to 5.17), presence of depression (adjusted OR 2.17, 95 % CI of 1.21 to 3.89), anxiety (adjusted OR 2.22; 95 % CI of 1.21 to 4.05) and alcohol use (adjusted OR 1.99; 95 % CI of 1.02 to 3.86) were positively associated with MCI while leisure activities at home (adjusted OR 0.33; 95 % CI of 0.11 to 0.95) were negatively associated.ConclusionThe prevalence of MCI is high in Kerala. It is important that the health system and the government take up urgent measures to tackle this emerging public health issue.
CD6 is associated with T-cell modulation and is implicated in several autoimmune diseases. We previously demonstrated that Itolizumab, a CD6 domain 1 (CD6D1) specific humanized monoclonal antibody, ...inhibited the proliferation and cytokine production by T lymphocytes stimulated with anti-CD3 antibody or when co-stimulated with ALCAM. Aberrant IL-17 producing CD4+ helper T-cells (Th17) have been identified as pivotal for the pathogenesis of certain inflammatory autoimmune disorders, including psoriasis. Itolizumab has demonstrated efficacy in human diseases known to have an IL-17 driven pathogenesis. Here, in in vitro experiments we show that by day 3 of human PBMC activation using anti-CD3 and anti-CD28 co-stimulation in a Th17 polarizing milieu, 15-35% of CD4+ T-cells overexpress CD6 and there is an establishment of differentiated Th17 cells. Addition of Itolizumab reduces the activation and differentiation of T cells to Th17 cells and decreases production of IL-17. These effects are associated with the reduction of key transcription factors pSTAT3 and RORγT. Further, transcription analysis studies in these conditions indicate that Itolizumab suppressed T cell activation by primarily reducing cell cycle, DNA transcription and translation associated genes. To understand the mechanism of this inhibition, we evaluated the effect of this anti-human CD6D1 mAb on ALCAM-CD6 as well as TCR-mediated T cell activation. We show that Itolizumab but not its F(ab')2 fragment directly inhibits CD6 receptor hyper-phosphorylation and leads to subsequent decrease in associated ZAP70 kinase and docking protein SLP76. Since Itolizumab binds to CD6 expressed only on human and chimpanzee, we developed an antibody binding specifically to mouse CD6D1. This antibody successfully ameliorated the incidence of experimental autoimmune encephalitis in the mice model. These results position CD6 as a key molecule in sustaining the activation and differentiation of T cells and an important target for modulating autoimmune diseases.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
Because the addition of nimotuzumab to chemoradiation in patients with locally advanced head and neck cancer improved outcomes in a phase 2 study, the authors conducted a phase 3 study to ...confirm these findings.
Methods
This open‐label, investigator‐initiated, phase 3, randomized trial was conducted from 2012 to 2018. Adult patients with locally advanced head and neck cancer who were fit for radical chemoradiation were randomized 1:1 to receive either radical radiotherapy (66‐70 grays) with concurrent weekly cisplatin (30 mg/m2) (CRT) or the same schedule of CRT with weekly nimotuzumab (200 mg) (NCRT).The primary endpoint was progression‐free survival (PFS); key secondary endpoints were disease‐free survival (DFS), duration of locoregional control (LRC), and overall survival (OS). An intent‐to‐treat analysis also was performed.
Results
In total, 536 patients were allocated equally to both treatment arms. The median follow‐up was 39.13 months. The addition of nimotuzumab improved PFS (hazard ratio HR, 0.69; 95% CI, 0.53‐0.89; P = .004), LRC (HR, 0.67; 95% CI, 0.50‐0.89; P = .006), and DFS (HR, 0.71; 95% CI, 0.55‐0.92; P = .008) and had a trend toward improved OS (HR, 0.84; 95% CI, 0.65‐1.08; P = .163). Grade 3 through 5 adverse events were similar between the 2 arms, except for a higher incidence of mucositis in the NCRT arm (66.7% vs 55.8%; P = .01).
Conclusions
The addition of nimotuzumab to concurrent weekly CRT improves PFS, LRC, and DFS. This combination provides a novel alternative therapeutic option to a 3‐weekly schedule of 100 mg/m2 cisplatin in patients with locally advanced head and neck cancer who are treated with radical‐intent CRT.
The addition of nimotuzumab to concurrent weekly cisplatin and chemoradiotherapy improves outcomes. This combination provides a novel alternative therapeutic option to a 3 weekly schedule of 100 mg/m2 cisplatin in patients with head and neck cancer.
Congenital adrenal hyperplasia (CAH) in children varies in presentation and progression with several challenges in optimal management. Effective treatment is to achieve normal growth and development ...while avoiding adrenal crisis and hyperandrogenisation.
Our aim was to ascertain the current practice in the UK on CAH management in children in comparison with the recommendations made by the Endocrine Society.
An online survey was emailed to the British Society of Paediatric Endocrinology (BSPED) members requesting a response from each centre regarding CAH management.
The survey was completed by 35 out of 92 centres (38% response rate). Tertiary centres constituted 22/35, while 8/35 were district general hospitals providing tertiary services. Treatment varied among centres with 25/35 using 10–15 mg/m
/day of hydrocortisone and 21/35 of centres using 50–150 μg/day of fludrocortisone. The frequency of clinical reviews was contentious and varied depending on the child’s age and clinical status. Reviews were done 3–4 monthly in 68% and 6 monthly in 31% of centres. The frequency of investigations including 17-hydroxyprogesterone (66% 3–6 monthly; 34% yearly), testosterone/dehydroepiandrosterone sulphate (37% 6 monthly; 51% yearly), renin/aldosterone (31% 6 monthly; 69% yearly) and bone age (83% yearly, 6% 2 yearly) varied significantly among centres. Genetic counselling was provided at diagnosis in 69% of the centres while surgical (66%) and psychology (80%) input were provided on an as required basis.
Our survey highlights the diversity in managing children with CAH in the UK as compared with the recommendations of the Endocrine Society. It also demonstrates inconsistent involvement of essential specialist services, which are essential for optimal management of this condition.
Periodontitis is a chronic inflammatory disease that results in the destruction of supporting tissue and bone leading to tooth mobility. Tooth mobility if untreated can lead to tooth loss. However, ...very few studies exist for its assessment. The aim of this study was to find out the prevalence of tooth mobility among patients visiting a tertiary care centre.
This descriptive cross-sectional study was conducted among individuals visiting a tertiary care dental hospital from 1st April to 30th June 2022 after obtaining ethical clearance from the Institutional Review Committee (Reference number: 2202202202). Individuals more than 13 years who gave consent and fulfilled the study criteria were enrolled. Tooth mobility was assessed using Lindhe and Nyman's classification. Proforma also included demographics, simplified oral hygiene index, gingival index, body mass index, and smoking status. Convenience sampling was done. Point estimate and 95% Confidence Interval were calculated.
Among 163 patients, 65 (39.88%) patients (32.36-47.40, 95% Confidence Interval) had tooth mobility.
The prevalence of tooth mobility was higher than in studies done in similar settings.
periodontitis; prevalence; tooth mobility.
A blemish free, even-toned skin is typically linked with healthy skin. Vyanga is one of diseases of skin that reduces the aesthetic worth of face to an extent. It is characterized by the presence of ...Niruja (painless), Tanu (light) and Shyava varna mandala (bluish black patches) on face. Although it is not a serious illness but it causes skin discoloration which stays on the face for a long time. In the era of competition, appearance of an individual gives self-confidence and linked with social status. On the contrary, Vyanga impact on individual’s psychological state and social relationship. The disease Vyanga can be correlated with hyperpigmentation with special reference to Melasma. Topical application is additional useful in Twaka Roga (skin disorder) as it directly acts on lesion and simple to use. Kanaka Taila is a classical ayurvedic skin oil formulation described in Chakradatta in the chapter named “Kshudra Roga” indicated in Abhiru, Nilika & Vyanga. It is useful in the treatment of oral diseases and to relieve skin scars and hyperpigmentation on the face. It also has mukhakantikar effect. This article reviews properties of various ingredients of Kanaka Taila which could help address Vyanga and its probable mode of action based on ayurvedic literature.
Health is one of the rising subjects utilized for surveying Health condition among patients who experience the ill effects of explicit sickness or infections. The Health searchers have numerous on ...the web and disconnected techniques to get the data mentioned by them. However, the network based Health administrations have a few characteristic impediments, for example, tedious for Health searchers and furthermore mitigate the specialists' remaining burden. In this way, programmed infection surmising is criticalness to conquer the trouble of online Health searcher. This work expects to fabricate a sickness recommendation conspire that can consequently gather the potential ailments of the given inquiries in network based Health administrations. Here propose a novel profound learning plan to induce the conceivable sickness given the subject of Health searchers. Our meagerly associated profound learning model contains five layers including the information and yield layers. The hubs in the info layer speak to crude highlights, and hubs in the yield layer mean the surmising results that are used to rough the genuine infection types. This model initially breaks down the data needs of Health searchers regarding inquiry and afterward selects those that pose for potential infections of their showed side effects for further explanatory. At that point client will look for their needs as inquiry. Next preprocesses the inquiry to locate the therapeutic qualities. At that point the preprocessed ascribes to distinguish the relating infection idea. Broad investigates a genuine world dataset named by online specialists show the noteworthy presentation additions of our plan.
The technique called signal processing is vitally used as a choice in the case of real-time examination of ECG (electrocardiography) signals. Classification of arrhythmic beat is primarily utilized ...in the detection of abnormalities normally found in electrocardiogram (ECG) and thus help in identifying problem occurred in heart. This work intentionally carryout, signal preprocessing of electroencephalography, feature extraction using statistical and wavelet and SVM-RFE established classification for arrhythmic is achieved to differentiate regular and irregular constituents of ECG. FFT technique, is used initially in order to remove the noise, to detect R-peaks later then the thresholding technique and windowing technique are consumed. The features of wavelet (such as the information of RR-interval) are calculated and sequenced to features of statistical to organize the final set of feature, which is then consumed to characterize and classify with SVM-RFE for ECG signals. The anticipated classification method arrhythmia is pragmatic to inputting electrocardiography signals gained from the database of MIT-BIH Arrhythmia, along with several international databases of ECG signal. There is no cross validation is required since SVM-RFE works healthy and thus it gives an outstanding performance, it will be beneficial for long-term electrocardiography beat analysis and classification. Results recommend that though the duration of the findings of the recording are of short, with the anticipated model which is able to analyze and classify the idiosyncrasies of heart from an ECG measuring unit with a single lead. The results obtained from the experiment shows an overall accuracy of high performance, sensitivity, and98.97% specificity in contrast with the current approaches mentioned in the literature.