Association between weight gain and knee osteoarthritis: a systematic review.

OBJECTIVE: Although weight loss is recommended to manage knee osteoarthritis (KOA), adults tend to gain weight with age which may affect KOA symptoms and progression. We conducted a systematic review and data synthesis to investigate the association between weight gain and KOA, defined by clinical features, structural progression, and total knee replacement (TKR). DESIGN: MEDLINE and EMBASE were systematically searched for controlled trials and cohort studies of participants with (or at risk of) KOA examining the relationship between weight gain and KOA clinical features (pain, function, quality of life), structural progression, and TKR. Risk of bias was assessed using the ROBINS-I tool. Results were organised by outcome, with meta-analyses performed where appropriate. RESULTS: Twenty-three studies were included. Results showed significant detrimental effects of weight gain on pain (4 of 7 studies), stiffness (2 of 2 studies), function (5 of 6 studies), and the single studies examining quality of life, and clinical and radiographic KOA. Weight gain adversely affected cartilage (6 of 9 studies), bone marrow lesions (1 of 4 studies), meniscal damage (1 of 3 studies) and effusion/synovitis (1 of 1 study). Weight gain significantly increased TKR (3 of 6 studies): meta-analysis of 2 with available data demonstrated significant increases in TKR/5 kg weight gain in women, HR 1.34 (95% CI 1.18-1.51), and in men, HR 1.25 (95% CI 1.16-1.34). CONCLUSIONS: Weight gain in adults is associated with increased clinical and structural KOA and TKR. Prevention of weight gain should be considered to improve outcomes in KOA.

Trajectories of body mass index from early adulthood to late midlife and incidence of total knee arthroplasty for osteoarthritis: findings from a prospective cohort study.

OBJECTIVE: To examine the association between body mass index (BMI) trajectories from early adulthood to late midlife and risk of total knee arthroplasty (TKA) for osteoarthritis. METHODS: 24,368 participants from the Melbourne Collaborative Cohort Study with weight collected during 1990-1994, 1995-1998, and 2003-2007, recalled weight at age 18-21 years, and height measured during 1990-1994 were included. Incident TKA from 2003 to 2007 to December 2018 was determined by linking cohort records to the National Joint Replacement Registry. RESULTS: Using group-based trajectory modelling, six distinct trajectories (TR) of BMI from early adulthood (age 18-21 years) to late midlife (approximately 62 years) were identified: lower normal to normal BMI (TR1; 19.7% population), normal BMI to borderline overweight (TR2; 36.7%), normal BMI to overweight (TR3; 26.8%), overweight to borderline obese (TR4; 3.5%), normal BMI to class 1 obesity (TR5; 10.1%), overweight to class 2 obesity (TR6; 3.2%). Over 12.4 years, 1,328 (5.4%) had TKA. The hazard ratios for TKA increased in all TR compared to TR1 [from TR2: 2.03 (95% CI 1.64-2.52) to TR6: 8.59 (6.44-11.46)]. 28.4% of TKA could be prevented if individuals followed the trajectory one lower, an average weight reduction of 8-12 kg from early adulthood to late midlife, saving $AUS 373 million/year. Most reduction would occur in TR2 (population attributable fraction 37.9%, 95% CI 26.7-47.3%) and TR3 (26.8%, 20.0-31.2%). CONCLUSIONS: Prevention of weight gain from young adulthood to late midlife in order to reduce overweight/obesity has the potential to significantly reduce the cost and burden of TKA.

Evidence of Antineutrinos from Distant Reactors Using Pure Water at SNO.

The SNO+ Collaboration reports the first evidence of reactor antineutrinos in a Cherenkov detector. The nearest nuclear reactors are located 240 km away in Ontario, Canada. This analysis uses events with energies lower than in any previous analysis with a large water Cherenkov detector. Two analytical methods are used to distinguish reactor antineutrinos from background events in 190 days of data and yield consistent evidence for antineutrinos with a combined significance of 3.5σ.

Metformin as a potential disease-modifying drug in osteoarthritis: a systematic review of pre-clinical and human studies.

OBJECTIVE: Osteoarthritis causes significant pain and disability with no approved disease-modifying drugs. We systematically reviewed the evidence from both pre-clinical and human studies for the potential disease-modifying effect of metformin in osteoarthritis. METHODS: Ovid Medline, Embase and CINAHL were searched between inception and June 2021 using MeSH terms and key words to identify studies examining the association between metformin use and outcome measures related to osteoarthritis. Two reviewers performed the risk of bias assessment and 3 reviewers extracted data independently. Qualitative evidence synthesis was performed. This systematic review is registered on PROSPERO (CRD42021261052 and CRD42021261060). RESULTS: Fifteen (10 pre-clinical and 5 human) studies were included. Most studies (10 pre-clinical and 3 human) assessed the effect of metformin using knee osteoarthritis models. In pre-clinical studies, metformin was assessed for the effect on structural outcomes (n = 10); immunomodulation (n = 5); pain (n = 4); and molecular pathways of its effect in osteoarthritis (n = 7). For human studies, metformin was evaluated for the effect on structural progression (n = 3); pain (n = 1); and immunomodulation (n = 1). Overall, pre-clinical studies consistently showed metformin having a chondroprotective, immunomodulatory and analgesic effect in osteoarthritis, predominantly mediated by adenosine monophosphate-activated protein kinase activation. Evidence from human studies, although limited, was consistent with findings in pre-clinical studies. CONCLUSION: We found consistent evidence across pre-clinical and human studies to support a favourable effect of metformin on chondroprotection, immunomodulation and pain reduction in knee osteoarthritis. Further high-quality clinical trials are needed to confirm these findings as metformin could be a novel therapeutic drug for the treatment of osteoarthritis.

Systematic review and meta-analysis of the prevalence of neuropathic-like pain and/or pain sensitization in people with knee and hip osteoarthritis.

OBJECTIVE: To determine the prevalence of neuropathic-like pain (NP) and pain sensitization (PS) defined by self-report questionnaires in knee and hip osteoarthritis, and whether prevalence is potentially explained by disease-severity or affected joint. DESIGN: MEDLINE, EMBASE, CINAHL were systematically searched (1990-April 2020) for studies describing the prevalence of NP and PS in knee and hip osteoarthritis using self-report questionnaires. Random-effects meta-analysis was performed. Statistical heterogeneity between studies and sub-groups (affected joint and population source as a proxy for disease severity) was assessed (I2 statistic and the Chi-squared test). RESULTS: From 2,706 non-duplicated references, 39 studies were included (2011-2020). Thirty-six studies reported on knee pain and six on hip pain. For knee osteoarthritis, the pooled prevalence of NP was: using PainDETECT, possible NP(score ≥13) 40% (95%CI 32-48%); probable NP(score >18) 20% (95%CI 15-24%); using Self-Report Leeds Assessment of Neuropathic Symptoms and Signs, 32% (95%CI 26-38%); using Douleur Neuropathique (DN4) 41% (95% CI 24-59%). The prevalence of PS using Central Sensitization Inventory (CSI) was 36% (95% CI 12-59%). For hip osteoarthritis, the pooled prevalence of NP was: using PainDETECT, possible NP 29% (95%CI 22-37%%); probable NP 9% (95%CI 6-13%); using DN4 22% (95%CI 12-31%) in one study. The prevalence of possible NP pain was higher at the knee (40%) than the hip (29%) (difference 11% (95% CI 0-22%), P = 0.05). CONCLUSIONS: Using self-report questionnaire tools, NP was more prevalent in knee than hip osteoarthritis. The prevalence of NP in knee and hip osteoarthritis were similar for each joint regardless of study population source or tool used. Whether defining NP using self-report questionnaires enables more effective targeted therapy in osteoarthritis requires investigation.

Does preoperative neuropathic-like pain and central sensitisation affect the post-operative outcome of knee joint replacement for osteoarthritis? A systematic review and meta analysis.

BACKGROUND: Almost a third of those undergoing knee replacement for osteoarthritis have poor outcomes despite technically successful surgery. Preoperative neuropathic-like pain and/or pain sensitisation may increase the risk of pain following joint replacement. OBJECTIVE: To examine whether preoperative neuropathic-like pain and pain sensitisation predicts pain, function and satisfaction following joint replacement for knee osteoarthritis. DESIGN: Systematic review with meta-analysis. METHODS: Medline, EMBASE and CINAHL were systematically searched until March 2020. Studies detecting neuropathic-like pain and/or sensitisation using self-report questionnaires prior to knee replacement for osteoarthritis, and relating this to post-operative outcomes were identified. Data extraction, risk of bias assessment and meta-analysis were performed, where appropriate. RESULTS: Five manuscripts, including one preprint, examining six cohorts were included: four used painDETECT or modified painDETECT, one the Self-Report Leeds Assessment of Neuropathic Symptoms and Signs, and another the Central Sensitisation Inventory to identify preoperative characteristics. Three studies showed preoperative neuropathic-like pain or sensitisation was associated with more intense post-operative pain. All four studies examining the risk of significant pain after knee replacement suggested it was increased after >3 months. The only study examining patient satisfaction and function found reduced satisfaction, but no difference in function in those with preoperative sensitisation. Meta-analysis found the relative risk of increased pain following knee replacement in those with neuropathic-like pain (painDETECT ≥13) to be 2.05 (95% confidence intervals 1.51, 2.79). CONCLUSION: These results provide consistent but limited evidence that self-report tools detecting neuropathic-like pain and/or pain sensitisation, predict patients at higher risk of pain following knee replacement.

Relationship of weight and obesity with the risk of knee and hip arthroplasty for osteoarthritis across different levels of physical performance: a prospective cohort study.

OBJECTIVE: To examine the association between obesity and knee and hip arthroplasty for osteoarthritis across a range of physical performance. METHOD: The body mass index and physical performance (on the 36-item Short Form Health Survey) of 9135 Australian Diabetes, Obesity and Lifestyle Study participants were measured in 1999-2000. The incidence of knee and hip arthroplasty during 2002-2011 was determined by linking the cohort records to the Australian Orthopaedic Association National Joint Replacement Registry. RESULTS: Over 9.1 ± 2.3 years (mean ± sd)) of follow-up, 317 participants had knee and 202 had hip arthroplasty for osteoarthritis. Using those with neither obesity nor significantly impaired physical performance as the reference group, participants with both obesity and significantly impaired physical performance had a higher knee arthroplasty risk [hazard ratio (HR) = 5.25, 95% confidence interval (CI) 3.85-7.14] than those with obesity alone (HR = 2.49, 95% CI 1.81-3.44) or impaired physical performance alone (HR = 2.19, 95% CI 1.59-3.02). Similar results were observed for hip arthroplasty (obesity and impaired physical performance: HR = 2.67, 95% CI 1.72-4.15; obesity alone: HR = 1.65, 95% CI 1.08-2.51; impaired physical performance alone: HR = 1.83, 95% CI 1.26-2.66). Among overweight/obese patients, 5 kg greater baseline weight increased the knee arthroplasty risk across all levels of physical performance, and hip arthroplasty risk in those with the highest level of physical performance. CONCLUSION: Although impaired physical performance is an independent risk factor for knee and hip arthroplasty, greater weight increased knee arthroplasty for overweight/obese participants at all levels of physical performance, but hip arthroplasty only in those with good physical performance. Targeting weight loss has the potential to reduce the risk of knee arthroplasty and improve patient outcomes, even in those with poor physical performance.

Female hormonal factors and osteoarthritis of the knee, hip and hand: a narrative review.

Osteoarthritis is a leading cause of disability with no cure. The incidence of osteoarthritis is sexually dimorphic: women have a higher rate of osteoarthritis than men after the age of 50. Research has investigated the contribution of sex hormones, reproductive factors and hormone supplementation to osteoarthritis. It has been recognized that different joints are susceptible to different risk factors for osteoarthritis. We reviewed the evidence for the effect of endogenous sex hormones, reproductive factors and hormone supplementation on joint-specific osteoarthritis of the knee, hip and hand. Although the role of these hormonal factors in the pathogenesis of osteoarthritis is complex, data suggest that endogenous hormones and reproductive factors have a role in the pathogenesis of osteoarthritis, especially knee osteoarthritis, with uncertainty for the effect of exogenous hormones. From the available data, it is hard to conclude whether this is a direct effect of hormonal factors, or whether other factors related to these hormonal factors, i.e. obesity and inflammation, have a role in this association. Further studies should consider the mediation effect of body weight and inflammation, change in body weight throughout life, circulatory levels of all endogenous hormones and circulatory levels of hormones after hormone supplementation in this complex relationship.

Relationship between circulating sex steroid hormone concentrations and incidence of total knee and hip arthroplasty due to osteoarthritis in men.

OBJECTIVE: Few studies have examined the association between circulating sex steroid concentrations and risk of osteoarthritis (OA) in men with inconsistent results. Our aim was to examine whether concentrations of circulating sex steroid hormones were associated with the incidence of primary knee and hip arthroplasty for OA in a prospective cohort study. DESIGN: Two thousand four hundred and ninety four men from the Melbourne Collaborative Cohort Study (MCCS) had circulating sex steroid concentrations measured in blood samples drawn at recruitment (1990-1994) and stored in liquid nitrogen. The plasma concentrations of sex hormones, including dehydroepiandrosterone sulphate, androstenedione, testosterone, estradiol, androstanediol glucuronide, and sex hormone binding globulin, were measured. The incidence of total knee and hip arthroplasty for OA during 2001-2013 was determined by linking MCCS records to the Australian Orthopaedic Association National Joint Replacement Registry. RESULTS: One hundred and four men had knee and 80 had hip arthroplasty for OA over 10.7 (SD 3.8) years. Higher concentrations of androstenedione were associated with a decreased risk of total knee (hazard ratio (HR) 0.87, 95% confidence interval (CI) 0.77-0.98) and hip (HR 0.84 95% CI 0.71-1.00) arthroplasty for OA in overweight and obese men. No significant association was observed for the other measured hormones. CONCLUSION: Low plasma androstenedione concentration is associated with an increased risk of both knee and hip arthroplasty for OA for overweight and obese men. While the findings need to be confirmed in other cohort studies, they suggest that circulating sex steroids may play a role in the pathogenesis of OA in men.

Management options for femoroacetabular impingement: a systematic review of symptom and structural outcomes.

OBJECTIVE: The optimal therapy for femoroacetabular impingement (FAI) is unclear. The aim of this systematic review was to examine the evidence for surgical and non-surgical treatment of FAI on symptom and structural outcomes. DESIGN: MEDLINE and EMBASE were searched electronically. Surgical and non-surgical management strategies were searched with "FAI". Studies which included comparison groups and reported symptom or structural outcomes were included (Levels I-III evidence). A risk of bias assessment was performed. RESULTS: Eighteen studies comparing management strategies for FAI were identified. Most studies had high risk of bias. No study compared surgical and non-surgical treatment. When surgical approaches were compared there was evidence of superior symptom outcomes with arthroscopy compared to open surgery and with labral preservation. There was some evidence that surgical interventions are effective in reducing alpha angle (improved hip shape), but no data on whether this affects long-term outcomes. There was some weak evidence that surgery is associated with structural progression of hip osteoarthritis (OA). CONCLUSIONS: Although evidence supports improvement in symptoms after surgery in FAI, no studies have compared surgical and non-surgical treatment. Therefore no conclusion regarding the relative efficacy of one approach over the other can be made. Surgery improves alpha angle but whether this alters the risk of development or progression of hip OA is unknown. This review highlights the lack of evidence for use of surgery in FAI. Given that hip geometry may be modified by non-surgical factors, clarifying the role of non-surgical approaches vs surgery for the management of FAI is warranted.

Estimation of genetic variability among peanut genotypes for resistance to leaf spot disease.

This study aimed to identify high-yielding peanut genotypes with resistance to leaf spot disease. The experiments included material from fourteen local and four exotic peanut genotypes that showed highly significant differences among morphological and disease severity parameters in all the genotypes which, in turn, suggested diversity genotypes. Disease severity analysis showed that the highest disease score and damaged leaf area were observed in the genotype Kelincer and the lowest scores and leaf damaged areas were observed in Majalaya super and BARI-2000, respectively. Based on these results, the genotypes BARI-2011, Chakori, Golden, BARI-89, Majalaya Super, BARD-699, BARI-2000, SP-1, and No. 334 can be used by breeders in peanut improvement programs for the development of new cultivars with higher disease resistance and increased yield.

Knee osteoarthritis: a review of management options.

Osteoarthritis of the knee is a complex peripheral joint disorder with multiple risk factors. The molecular basis of osteoarthritis has been generally accepted; however, the exact pathogenesis is still not known. Management of patients with osteoarthritis involves a comprehensive history, thorough physical examination and appropriate radiological investigation. The relative slow progress in the disease allows a stepwise algorithmic approach in treatment. Non-surgical treatment involves patient education, lifestyle modification and the use of orthotic devises. These can be achieved in the community. Surgical options include joint sparing procedures such as arthroscopyando osteotomy or joint-replacing procedures. Joint-replacing procedures can be isolated to a single compartment such as patellofemoral arthroplasty or unicompartmental knee replacement or total knee arthroplasty. The key to a successful long-term outcome is optimal patient selection, preoperative counselling and good surgical technique.

Association between serum concentration of 25-hydroxyvitamin D and the risk of hip arthroplasty for osteoarthritis: result from a prospective cohort study.

OBJECTIVES: There is ongoing debate regarding the optimal serum concentrations of 25-hydroxy-vitamin D for musculoskeletal health, including osteoarthritis (OA). The aim of this prospective cohort study was to determine whether serum 25-hydroxy-vitamin D concentrations were associated with the risk of hip arthroplasty for OA. DESIGN: This study examined 9135 participants from the Australian Diabetes, Obesity and Lifestyle Study who had serum 25-hydroxy-vitamin D measured in 1999-2000 and were aged ≥40 years at the commencement of arthroplasty data collection. The incidence of hip arthroplasty for OA during 2002-2011 was determined by linking cohort records to the Australian Orthopaedic Association National Joint Replacement Registry. RESULTS: Over an average 9.1 (standard deviation (SD) 2.7) years of follow-up, 201 hip arthroplasties for OA were identified (males n = 90; females n = 111). In males, a one-standard-deviation increase in 25-hydroxy-vitamin D was associated with a 25% increased incidence (HR 1.25, 95% CI 1.02-1.56), with a dose response relationship evident by quartiles of 25-hydroxy-vitamin D concentration (P for trend 0.04). These results were independent of age, body mass index (BMI), ethnicity, smoking status, physical activity, season of blood collection, latitude, hypertension and diabetes, area level disadvantage or after excluding those with extreme low 25-hydroxy-vitamin D concentrations. No significant association was observed in women (HR 1.10, 95% CI 0.87, 1.39). CONCLUSIONS: Increasing serum 25-hydroxy-vitamin D concentrations were associated with an increased risk of hip arthroplasty for OA in males, while no significant association was observed in females. The mechanism for the association warrants further investigation.

Retinal arteriolar narrowing and incidence of knee replacement for osteoarthritis: a prospective cohort study.

OBJECTIVES: The role of the microcirculation in the pathogenesis of osteoarthritis (OA) remains unclear. This prospective cohort study examined the association between retinal vascular calibre and incidence of knee replacement for OA. DESIGN: 1838 participants of the Australian Diabetes, Obesity and Lifestyle (AusDiab) Study had retinal vascular calibre measured using a nonmydriatic digital fundus camera in 1999-2000 and were aged ≥ 40 years at joint replacement data collection commencement. The incidence of knee replacement for OA during 2002-2011 was determined by linking cohort records to the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR). RESULTS: 77 participants underwent knee replacement for OA. They had narrower retinal arteriolar calibre compared with those without knee replacement (166.1 ± 24.8 µm vs 174.3 ± 24.5 µm, P = 0.004). For every one standard deviation reduction in retinal arteriolar calibre, the incidence of knee replacement increased by 25% (HR 1.25, 95% confidence interval (CI) 1.00-1.56). Participants in the narrower two-thirds of arteriolar calibre had twice the risk of knee replacement compared with those in the widest one-third (HR 2.00, 95% CI 1.07-3.74, P = 0.03) after adjustment for sex, body mass index (BMI), physical activity and HbA1c. There was no association for retinal venular calibre. CONCLUSIONS: Retinal arteriolar narrowing is associated with increased risk of knee replacement for OA suggesting that further work is warranted to determine the role of the microcirculation in the pathogenesis of knee OA.

Modified Tilt-integral active disturbance rejection controller with inertia emulated direct current link for frequency control of marine microgrid.

The increasing integration of intermittent renewable sources (RSs) poses a dynamic frequency stability challenge for modern marine vessel microgrids. To address this issue, this paper proposes a novel control approach, specifically targeting frequency and tie-line power stabilization in a diverse source marine microgrid (MµG) with two intertied areas featuring renewable (wind-wave) sources. The suggested approach introduces a modified tilt-integral active disturbance rejection (TI-ADRC) controller designed to ensure effective damping of power frequency oscillations. As the control scheme depends on the optimal setting of the proposed controller, a recently developed marine predator technique (MPT) has been adopted. The performance of the proposed controller is compared with other recent controllers viz. PID, tilt-integral derivative (TID), two-degree-of-freedom (2DOF)-PID, fuzzy-PI, and ADRC to validate its superiority. To further enhance the system dynamics, a precise modeling of inertia emulated direct current (IEPDC) tie link is incorporated in microgrid system. The impact assessments, considering time delays with pre/post IEPDC link, demonstrate a substantial 57.79% and 81.53% reduction in peak frequency overshoot compared to DC link (conventional model) and AC link, respectively. The analysis of the eigen plot confirms the stability of the control system. Sensitivity assessments of the controller against ± 30% parametric variations and load fluctuations are conducted, affirming its robustness. Finally, the result from OPAL-RT confirm the practicality of the proposed method. It is asserted that the suggested controller is reliable and functions well in n the presence of diverse disruptions and parametric variations.

Loose body following cross-pin fixation for anterior cruciate ligament reconstruction.

We report a case of loosening of a bioabsorbable cross-pin fixation device for anterior cruciate ligament reconstruction. Forty-two months following a bone tendon bone reconstruction of the anterior cruciate ligament, the patient presented with a subcutaneous collection in the medial side of the knee. At subsequent surgery, a RIGIDFIX cross-pin fixator (Mitek, Westwood, MA, USA) was retrieved, intact, from the sterile fluctuant mass around the superomedial aspect of the knee. The graft was stable both radiologically and clinically, and the patient remains symptom free. This case raises concern about the use of this smooth cross-pin fixator and the consequences of backing out and the resultant intraarticular loose body. We suggest consideration of a loose body if the patient becomes symptomatic postoperatively, and early intervention to prevent chondral damage is recommended.

A novel hybrid methodology to secure GOOSE messages against cyberattacks in smart grids.

IEC 61850 is emerging as a popular communication standard for smart grids. Standardized communication in smart grids has an unwanted consequence of higher vulnerability to cyber-attacks. Attackers exploit the standardized semantics of the communication protocols to launch different types of attacks such as false data injection (FDI) attacks. Hence, there is a need to develop a cybersecurity testbed and novel mitigation strategies to study the impact of attacks and mitigate them. This paper presents a testbed and methodology to simulate FDI attacks on IEC 61850 standard compliant Generic Object-Oriented Substation Events (GOOSE) protocol using real time digital simulator (RTDS) together with open-source tools such as Snort and Wireshark. Furthermore, a novel hybrid cybersecurity solution by the name of sequence content resolver is proposed to counter such attacks on the GOOSE protocol in smart grids. Utilizing the developed testbed FDI attacks in the form of replay and masquerade attacks on are launched and the impact of attacks on electrical side is studied. Finally, the proposed hybrid cybersecurity solution is implemented with the developed testbed and its effectiveness is demonstrated.

The relationship between long-term blood pressure variability and cortical thickness in older adults.

High blood pressure variability (BPV) is a risk factor for cognitive decline and dementia, but its association with cortical thickness is not well understood. Here we use a topographical approach, to assess links between long-term BPV and cortical thickness in 478 (54% men at baseline) community dwelling older adults (70-88 years) from the ASPirin in Reducing Events in the Elderly NEURO sub-study. BPV was measured as average real variability, based on annual visits across three years. Higher diastolic BPV was significantly associated with reduced cortical thickness in multiple areas, including temporal (banks of the superior temporal sulcus), parietal (supramarginal gyrus, post-central gyrus), and posterior frontal areas (pre-central gyrus, caudal middle frontal gyrus), while controlling for mean BP. Higher diastolic BPV was associated with faster progression of cortical thinning across the three years. Diastolic BPV is an important predictor of cortical thickness, and trajectory of cortical thickness, independent of mean blood pressure. This finding suggests an important biological link in the relationship between BPV and cognitive decline in older age.

Modeling and prediction of KSE - 100 index closing based on news sentiments: an applications of machine learning model and ARMA (p, q) model.

The main financial markets of every country are stock exchange and consider as an imperative cause for the corporations to increase capital. The novelty of this study to explore machine learning techniques when applied to financial stock market data, and to understand how machine learning algorithms can be applied and compare the result with time series analysis to real lifetime series data and helpful for any investor. Investors are constantly reviewing past pricing history and using it to influence their future investment decisions. The another novelty of this study, using news sentiments, the values will be processed into lists displaying and representing the stock and predicting the future rates to describe the market, and to compare investments, which will help to avoid uncertainty amongst the investors regarding the stock index. Using artificial neural network technique for prediction for KSE 100 index data on closing day. In this regard, six months' data cycle trained the data and apply the statistical interference using a ARMA (p, q) model to calculate numerical result. The novelty of this study to find the relation between them either they are strongly correlated or not, using machine learning techniques and ARMA (p, q) process to forecast the behavior KSE 100 index cycles. The adequacy of model describes via least values Akaike information criterion (AIC), Bayesian Schwarz information criterion (SIC) and Hannan Quinn information criterion (HIC). Durbin- Watson (DW) test is also applied. DW values (< 2) shows that all cycles are strongly correlated. Most of the KSE-100 index cycles expresses that the appropriate model is ARMA (2,1). Cycle's 2nd,3rd,4th and 5th shows that ARMA (3,1) is best fitted. Cycle 8th is shows ARMA (1,1) best fit and cycle 12th shows that the most appropriate model is ARMA (4,1). Diagnostic checking tests like Root Mean Squared Error (RMSE), Mean Absolute Error (MAE), Mean Absolute Percentage Error (MAPE) and Theil's U-Statistics are used to predict KSE-100 index cycles. Theil's U-Statistics demonstrate that each cycle is strongly correlated to previous one.

Cognition enhancing effect of rosemary (Rosmarinus officinalis L.) in lab animal studies: a systematic review and meta-analysis.

Patients with mild cognitive impairment eventually progress to Alzheimer's disease (AD) causing a strong impact on public health. Rosmarinus officinalis has long been known as the herb of remembrance and can be a potential cognition enhancer for AD. The aim of this review was to summarize the qualitative and quantitative aspects of R. officinalis and its active constituents in enhancing cognition. A structured search was conducted on Google Scholar and PubMed to find relevant studies that assessed the effect of R. officinalis extract or any of its active constituents on cognitive performance in animals. The following information was extracted from each study: 1) article information; 2) characteristics of study animals; 3) type of intervention: type, dose, duration, and frequency of administration of R. officinalis; and 4) type of outcome measure. Data were analyzed using Review Manager and meta-analysis was performed by computing the standardized mean difference. Twenty-three studies were selected for qualitative analysis and fifteen for meta-analysis. From the fifteen included papers, 22 with 35 comparisons were meta-analyzed. Effect sizes for intact and cognitively impaired animals were 1.19 (0.74, 1.64) and 0.57 (0.19, 0.96), indicating a positive effect on both groups. The subgroup analyses showed substantial unexplained heterogeneity among studies. Overall, R. officinalis improved cognitive outcomes in normal and impaired animals, and results were robust across species, type of extract, treatment duration, and type of memory. However, studies had a considerable amount of heterogeneity, and subgroup analyses failed to find any heterogeneity moderator.