Evaluation of Nootropic Potential of Aerva persica Roots against D-galactose-induced Memory Impairment.

BACKGROUND: The primary phytoconstituents reported to have neuroprotective effects are flavonoids and phenolic compounds. Aerva persica roots are reported to be rich in flavonoids and phenolic compounds. Therefore, this study aimed to explore the nootropic potential of Aerva persica roots. OBJECTIVE: The objective of this study was to evaluate the nootropic potential of Aerva persica roots against D-galactose-induced memory impairment. METHODS: In this study, the roots of Aerva persica were extracted with 70% ethanol. The obtained extract was evaluated for total phenolic content using the Folin-Ciocalteu method and total flavonoid content using the aluminium chloride colorimetric assay. Afterward, the acute oral toxicity of the extract was determined following the Organisation for Economic Co-operation and Development (OECD) guideline 423. Additionally, two doses of Aerva persica (100 and 200 mg/kg body weight (BW)) were evaluated for their nootropic potential against D-galactose-induced memory impairment. The nootropic potential of the crude extract was assessed through a behavioural study and brain neurochemical analysis. Behavioural studies involved the evaluation of spatial reference- working memory using the radial arm maze test and the Y-maze test. Neurochemical analysis was performed to determine the brain's acetylcholine, acetylcholinesterase, glutathione (GSH), and malondialdehyde (MDA) levels. RESULTS: The total phenolic content and total flavonoid content were found to be 179.14 ± 2.08 µg GAE/mg and 273.72 ± 3.94 µg QE/mg, respectively. The Aerva persica extract was found to be safe up to 2000 mg/kg BW. Following the safety assessment, the experimental mice received various treatments for 14 days. The behavioural analysis using the radial maze test showed that the extract at both doses significantly improved spatial reference-working memory and reduced the number of total errors compared to disease control groups. Similarly, in the Y-maze test, both doses significantly increased the alteration percentage and the percentage of novel arm entry (both indicative of intact spatial memory) compared to disease control. In neurochemical analysis, Aerva persica at 200 mg/kg significantly normalised the acetylcholine level (p<0.0001) and GSH level (p<0.01) compared to disease control. However, the same effect was not observed with Aerva persica at 100 mg/kg. Additionally, Aerva persica at 200mg/kg BW significantly decreased the acetylcholinesterase level (p<0.0001) and decreased the brain's MDA level (p<0.01) compared to the disease control, whereas the effect of Aerva persica at 100 mg/kg BW in reducing acetylcholinesterase was non-significant. CONCLUSION: Based on the results, it can be concluded that the nootropic potential of Aerva persica was comparable to that of the standard drug, Donepezil, and the effect might be attributed to the higher content of flavonoids and phenolic compounds.

In silico analysis and experimental validation shows negative correlation between miR-1183 and cell cycle progression gene 1 expression in colorectal cancer.

MicroRNAs (miRNAs) are small noncoding RNAs that post-transcriptionally regulate gene expression by binding to the 3' untranslated regions (UTR) of target genes. Aberrant expression of miRNAs can lead to disease, including cancer. Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths worldwide. Among several factors, differential expression of miRNA can have serious consequences on disease progression. This study was designed to computationally identify and experimentally verify strong miRNA candidates that could influence CRC progression. In silico analysis of publicly available gene expression microarray datasets revealed significant upregulation of miR-1183 in CRC. Comparison of mRNA microarray expression data with predicted miR-1183 targets led to the identification of cell cycle progression gene 1 (CCPG1) as strong, negatively correlated miR-1183 target. Expression analysis by means of quantitative PCR validated the inverse correlation between miR-1183 and CCPG1 in colorectal cancer tissues. CCPG1 indirectly modulates the cell cycle by interacting with the PH/DH domain of Dbs (Rho-specific guanine nucleotide exchange factor). Interestingly, the computational analysis also showed that miR-1183 is upregulated in liver and gastric cancer. This finding is notable as the liver and stomach are the primary metastatic sites for colorectal cancer and hepatocellular carcinoma respectively. This novel finding highlights the broader implications of miR-1183 dysregulation beyond primary CRC, potentially serving as a valuable prognostic marker and a therapeutic target for both primary and metastatic CRC.

Euglycemic Diabetic Ketoacidosis in a Sedated Patient after Coronary Artery Bypass Grafting: A Case Report and Literature Review.

Euglycemic diabetic ketoacidosis (EDKA) is a rare and serious adverse effect of sodium-glucose cotransporter 2 inhibitors (SGLT-2i). The diagnosis is challenging due to the rarity, nonspecific symptoms, and absence of the alarmingly high blood glucose levels, and thus, it could be initially missed resulting in delayed treatment. This is particularly important for sedated patients, as the absence of typical clinical signs and symptoms can obscure the diagnosis. We present the case of a patient with type 2 diabetes mellitus on empagliflozin who developed EDKA while sedated after coronary artery bypass grafting (CABG) despite stopping the medication 24 hours prior to surgery. We also summarize the current literature on EDKA after CABG. Physicians must be aware and maintain a high index of suspicion for the illness, especially in patients with T2DM taking SGLT-2i and undergoing a major operation such as CABG. Emergent treatment and multidisciplinary follow-up are needed to improve patient outcomes and mitigate complications. Physicians should also consider identifying the optimal time to discontinue SGLT-2i before major surgeries and possible ketone studies in such patients, especially those sedated following the surgery.

Immunohistochemical Expression of CD10, BCL6 and MUM1 in Differentiating Diffuse Large B Cell Lymphoma Subtypes.

OBJECTIVE: To determine the immunohistochemical expression of CD10, BCL6 and MUM1 in differentiating diffuse large B cell lymphoma subtypes. STUDY DESIGN: Descriptive, cross-sectional study. PLACE AND DURATION OF STUDY: Department of Histopathology, Armed Forces Institute of Pathology, Rawalpindi, from November 2014 to May 2015. METHODOLOGY: Newly diagnosed cases of DLBCLon H&E stain as well as IHC markers, according to WHO blue book 2008, were included in the study. Patients' gender, age and site of lymphoma were noted. DLBCLsubtypes (GCB and activated type or non-GCB) were assessed based on IHC expression of CD10, BCL6 and MUM1 and the results were recorded. The data were analyzed by using computer software program SPSS version 20. Descriptive statistics, frequencies and percentages were calculated. RESULTS: Out of 96 patients, 79 (82%) were male and 17 (18%) were female. Mean age was 54.66 ±16.73 years. Thirty-six (37.5%) cases showed positivity for CD10 and BCL6 both (GCB type), whereas MUM1 was positive in 60 (62.5%) cases (non-GCB type or activated type). Asignificant statistical association was seen between expression of IHC markers (CD10, BCL6 and MUM1) and DLBCLsubtypes (GCB and non-GCB type, p<0.001). CONCLUSION: In Pakistani population, the frequency of non-GCB type expressing MUM1 is 62.5%, which is quite high as compared to western countries. It needs to be further explored, because it represents high-risk subsets in which alternative strategies for diagnosis and management should be planned.

Immunohistochemical Expression of Epidermal Growth Factor Receptor in Head and Neck Squamous Cell Carcinoma.

OBJECTIVE: To determine the frequency of expression of epidermal growth factor receptor (EGFR) by immunohistochemistry in head and neck squamous cell carcinoma (HNSCC). STUDY DESIGN: Cross-sectional study. PLACE AND DURATION OF STUDY: Armed Forces Institute of Pathology (AFIP), Rawalpindi, from September 2015 to March 2016. METHODOLOGY: Fifty-two cases of head and neck squamous cell carcinoma diagnosed on H&E stain were included in the study. Patients' gender and age were noted. Immunohistochemistry for EGFR was applied and the results were recorded. The data were analyzed by using computer software program SPSS version 19. Descriptive statistics, frequencies and percentages were calculated. RESULTS: Out of the 52 patients of HNSCC, 37 patients were males and 15 females. The age of the patients was between 21 and 80 years with an average age of 58.58 ±12.63. Out of 52 cases, 45 cases (86.53%) were positive for EGFR while 7 cases (13.46%) were negative for EGFR. Significant statistical association was not seen between the tumour grade and EGFR expression (p=0.162). CONCLUSION: The high expression of EGFR in head and neck cancers among Pakistani patients suggests its value as a therapeutic target. EGFR inhibitors have become well-known part of HNSCC treatment; therefore, patients with EGFR positive HNSCC can be benefitted from the therapy.

Bilateral Giant Cell Arteritis Presenting as Bilateral Sudden Vision Loss.

Giant cell arteritis (GCA) is the most common form of primary vasculitis and it mainly involves large to medium sized vessels. It is also referred to as temporal arteritis as it primarily affects the temporal artery. Ocular involvement frequently occurs in GCA; if not promptly diagnosed, it can cause devastating ocular complications including complete vision loss and permanent blindness. In the majority of cases, it is unilateral; however, there are rare instances where bilateral ocular involvement is reported. In our report, we present the case of a patient presenting with bilateral sudden vision loss associated with GCA.

Maximum entropy based common spatial patterns for motor imagery classification.

The common spatial pattern (CSP) is extensively used to extract discriminative feature from raw Electroencephalography (EEG) signals for motor imagery classification. The CSP is a statistical signal processing technique, which relies on sample based covariance matrix estimation to give discriminative information from raw EEG signals. The sample based estimation of covariance matrix becomes a problem when the number of training samples is limited, which causes the performance of CSP based brain computer interface (BCI) to degrade significantly. In this paper, we present a maximum entropy based CSP algorithm that incorporates principle of maximum entropy while estimating the sample based covariance matrix. The proposed algorithm is evaluated on publicly available data set samples. The classification results indicate that the proposed algorithm outperforms the traditional CSP algorithm by 13.38% on average.

Phytofabrication of bioinduced silver nanoparticles for biomedical applications.

Synthesis of nanomaterials holds infinite possibilities as nanotechnology is revolutionizing the field of medicine by its myriad applications. Green synthesis of nanoparticles has become the need of the hour because of its eco-friendly, nontoxic, and economic nature. In this study, leaf extract of Rosa damascena was used as a bioreductant to reduce silver nitrate, leading to synthesis of silver nanoparticles (AgNPs) in a single step, without the use of any additional reducing or capping agents. The synthesized nanoparticles were characterized by the use of UV-visible spectroscopy, fourier transform infrared spectroscopy, dynamic light scattering, transmission electron microscopy, and field emission scanning electron microscopy. Time-dependent synthesis of AgNPs was studied spectrophotometrically. Synthesized AgNPs were found to possess flower-like spherical structure where individual nanoparticles were of 16 nm in diameter, whereas the agglomerated AgNPs were in the range of 60-80 nm. These biologically synthesized AgNPs exhibited significant antibacterial activity against Gram-negative bacterial species but not against Gram-positive ones (Escherichia coli and Bacillus cereus). Anti-inflammatory and analgesic activities were studied on a Wistar rat model to gauge the impact of AgNPs for a probable role in these applications. AgNPs tested positive for both these activities, although the potency was less as compared to the standard drugs.

Clinical experience with insulin detemir, biphasic insulin aspart and insulin aspart in people with type 2 diabetes: Results from the Central Saudi Arabia cohort of the A1chieve study.

BACKGROUND: The A1chieve, a multicentric (28 countries), 24-week, non-interventional study evaluated the safety and effectiveness of insulin detemir, biphasic insulin aspart and insulin aspart in people with T2DM (n = 66,726) in routine clinical care across four continents. MATERIALS AND METHODS: Data was collected at baseline, at 12 weeks and at 24 weeks. This short communication presents the results for patients enrolled from Central Saudi Arabia. RESULTS: A total of 2819 patients were enrolled in the study. Four different insulin analogue regimens were used in the study. Study patients had started on or were switched to biphasic insulin aspart (n = 1100), insulin detemir (n = 1156), insulin aspart (n = 34), basal insulin plus insulin aspart (n = 314) and other insulin combinations (n = 170). At baseline glycaemic control was poor for both insulin naïve (mean HbA1c: 9.9%) and insulin user (mean HbA1c: 9.8%) groups. After 24 weeks of treatment, both the groups showed improvement in HbA1c (insulin naïve: -2.6%, insulin users: -2.5%). SADRs including major hypoglycaemic events did not occur in the study patients. CONCLUSION: Starting or switching to insulin analogues was associated with improvement in glycaemic control with a low rate of hypoglycaemia.

The target-specific transporter and current status of diuretics as antihypertensive.

The currently available diuretics increase the urinary excretion of sodium chloride by selective inhibition of specific sodium transporters in the loop of Henle and distal nephron. In recent years, the molecular cloning of the diuretic-sensitive sodium transporters at distal convoluted tubule has improved our understanding of the cellular mechanisms of action of each class of diuretics. Diuretics are tools of considerable therapeutic importance. First, they effectively reduce blood pressure. Loop and thiazide diuretics are secreted from the proximal tubule via the organic anion transporter-1 and exert their diuretic action by binding to the Na(+)-K(+)-2Cl(-) co-transporter type 2 in the thick ascending limb and the Na(+)-Cl(-) co-transporter in the distal convoluted tubule, respectively. Recent studies in animal models suggest that abundance of these ion transporters is affected by long-term diuretic administration. The WHO/ISH guidelines point out that diuretics enhance the efficacy of antihypertensive drugs and will most often be a component of combination therapy.

Frequency of hearing loss among textile industry workers of weaving unit in Karachi, Pakistan.

OBJECTIVE: To determine the frequency of hearing loss among textile industry workers of weaving department. To record the noise level in the weaving sections and to compare it with the international standards. To determine the awareness about the effects of noise on hearing amongst the workers and the protective measures adopted by them. METHODS: A cross-sectional study was carried out at weaving department of five renowned textile industries of Karachi. The study included 248 workers exposed to noise, through non-probability convenient sampling technique. Equivalent sound pressure level Leq was measured with the help of a Class-1 type digital sound level meter. Hearing status of the workers was assessed through questionnaire and clinical tests (WHISPER, RINNE'S and WEBER). RESULT: Results showed that noise level was in range of 88.4-104 dB(A). The questionnaire results showed that: (i) 92.7% of the workers were aware that high noise level cause speech interference. (ii) 57.2% were unaware about the effect of noise on health. (iii) 54.8% used ear protection devices. (iv) 22.5% did not respond well to whisper test while 16.9% were found to have defective hearing on the basis of Rinne's test and 17.4% through Weber's test. It was observed that hearing loss was significantly associated with working experience of more than 10 years (25%) and overtime (28.8%). CONCLUSION: The results of study establish the fact that noise level is more than acceptable limit of 85 dB(A) for 8 hours exposure stipulated by OSHA.There is an immediate need to develop and implement noise regulations in Pakistan.