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Background: Umbilical vein catheterization (UVC) is an early venous access route in newborns and is frequently used for delivering total parenteral nutrition (TPN) and medications. Vascular, hepatic parenchymal, and infectious complications of UVC can be seen rarely. Objective: We present preterm neonates' X-ray, US, and MRI findings with parenchymal TPN extravasation and portal vein thrombosis. Our case was the first case about MRI findings of TPNoma Case Presentation: A 30 week female with a birth weight of 1340 g was born via Cesarean section. Because of the diagnosis of transient tachypnea of the newborn and prematurity, the infant was hospitalized in the neonatal intensive care unit. On the first day of hospitalization, UVC was inserted and TPN with 20% lipid content was started. After 10 days, UVC was removed and TPN treatment was continued with a piccline catheter. Abdominal US and portal venous Doppler examination was applied to the patient whose general condition deteriorated on the 12th day. US and Doppler revealed a lesion of 17x17x18mm in size with lobulated contour, hyperechoic heterogeneous internal structure, and no central or peripheral blood supply was observed in the left lobe of the liver. Moreover, a filling defect compatible with a thrombus was observed in the proximal part of the left portal vein. An abdominal MRI was performed to characterize this liver lesion. Axial T1 weighted and T2- weighted images showed a heterogeneous hyperintense lesion without contrast enhancement. Axial fat saturation T1-weighted and out of phase T1-weighted images showed a reduction in signal intensity. US and MRI examinations showed that the thrombosed umbilical vein ended superior to the lesion. In the differential diagnoses, fat-containing lesions such as lipoma-teratoma and fat-containing collection secondary to extravasation of TPN treatment via UVC were thought. Conclusion: In the differential diagnosis of liver localized lesions in newborns, UVC-related liver injury should be considered and the localization of the catheter tip should be checked. In case of the doubt based on US and X-ray findings, presence of fat on MRI could be diagnostic. Serious complications should be avoided with catheter revision or removal.

Leiomyosarcoma is a malignant mesenchymal tumour of smooth muscle origin. It is extremely rare as a primary thyroid cancer with only 33 cases previously described in the literature. We present the case of a 69-year-old Caucasian man who presented with a 5-month history of left cervical lymphadenopathy and a suspicious mass in the left thyroid lobe on ultrasound scan. Left hemithyroidectomy confirmed the diagnosis of leiomyosarcoma. A review of current understanding and approaches to management of this rare condition are discussed.

Background: Peganum harmala is traditionally used to manage rheumatoid arthritis (RA) and other inflammatory conditions. However, its use against RA has not been scientifically evaluated. The current study was designed to assess the anti-arthritic and anti-inflammatory activities of the methanolic extract of P. harmala leaves by in vitro and in vivo methods. Methods: The in vitro assays were carried out to determine the effect of plant extract on inhibition of egg albumin denaturation and human red blood cell membrane (HRBC) stabilization. Moreover, 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity was performed to determine the antioxidant potential. In vivo anti-arthritic activity was performed by determining the curative effect against Complete Freund’s adjuvant (0.1 ml). The plant extract was administered to rats orally at 200, 400 and 600 mg/kg/day for 21 days. Results: The values of IC50 of plant extract in protein denaturation, stabilization of HRBC and DPPH assays were 77.54 mg/ml, 23.90 mg/ml and 58.09 µg/ml respectively. Moreover, the plant extract significantly attenuated the poly-arthritis and weight loss, anemia and paw edema. The plant extract restored the level of C-reactive protein, rheumatoid factor, alanine transaminase, aspartate transaminase and alkaline phosphatase in poly-arthritic rats. Moreover, the plant extract restored the immune organs weight in treated rats. Treatment with P. harmala also significantly subdued the oxidative stress by reinstating superoxide dismutase, reduced glutathione, catalase and malondialdehyde in poly-arthritic rats. The plant extract notably restored the prostaglandin-E2 and tumor necrosis factor (TNF)-α in the serum of poly-arthritic rats. Conclusion: It was concluded that P. harmala extract had potential antioxidant, anti-inflammatory and antiarthritic activities which primarily might be attributed to alkaloids, flavonoids and phenols.

Oxidative stress caused by the imbalance between production of oxidants and antioxidants in the body leads to the development of different ailments. The bioactive compounds derived from marine sources are considered to be safe and appropriate to use. Astaxanthin possesses antioxidant activity about 100–500 times higher than other antioxidants such as α‐tocopherol and β‐carotene. It has numerous health benefits and vital pharmacological properties for the treatment of diseases like diabetes, hypertension, cancer, heart disease, ischemia, neurological disorders, and potential role in liver enzyme gamma‐glutamyl transpeptidase which has significance in medicine as a diagnostic marker. The primary source of astaxanthin among crustaceans is shrimps and the presence of astaxanthin protects shrimps from oxidation of polyunsaturated fatty acids and cholesterol. Conclusively, astaxanthin derived from shrimps is very effective against oxidative stress which can lead to certain ailments., Conclusively, the astaxanthin derived from shrimps is very effective against oxidative stress which become the cause of certain ailments.

The specialty of geriatric medicine developed in the 1950s as a response to the particular health needs of frail older people since then the dental care for geriatric patients has been increasing day by day. The treatment and diagnosis of geriatric patient is challenging, as these patient have both systemic and oral problem. There is an escalating demand for geriatric oral healthcare in all developed and developing countries including India. Two-thirds of the world’s elderly live in developing countries. This is a huge population that must receive attention from policy-makers who will be challenged by the changing demands for social and health services including oral health services. Viewing the recent Indian demographic profile and the trends in oral health, pertinent policy subjects have to be discuss concerning the oral health needs of the elderly and also the associated challenges which include strategies to improve quality of life, strategies to train and educate the dental workforce and above all the role of healthcare systems towards realization of better aged society in India and other developing countries. Keywords: Geriatric dentistry, general health, oral health.

Malaria microscopy, microscopic examination of stained blood slides to detect parasite Plasmodium, is considered to be a gold-standard for detecting life-threatening disease malaria. Detecting the plasmodium parasite requires a skilled examiner and may take up to 10 to 15 minutes to completely go through the whole slide. Due to a lack of skilled medical professionals in the underdeveloped or resource deficient regions, many cases go misdiagnosed; resulting in unavoidable complications and/or undue medication. We propose to complement the medical professionals by creating a deep learning-based method to automatically detect (localize) the plasmodium parasites in the photograph of stained film. To handle the unbalanced nature of the dataset, we adopt a two-stage approach. Where the first stage is trained to detect blood cells and classify them into just healthy or infected. The second stage is trained to classify each detected cell further into the life-cycle stage. To facilitate the research in machine learning-based malaria microscopy, we introduce a new large scale microscopic image malaria dataset. Thirty-eight thousand cells are tagged from the 345 microscopic images of different Giemsa-stained slides of blood samples. Extensive experimentation is performed using different CNN backbones including VGG, DenseNet, and ResNet on this dataset. Our experiments and analysis reveal that the two-stage approach works better than the one-stage approach for malaria detection. To ensure the usability of our approach, we have also developed a mobile app that will be used by local hospitals for investigation and educational purposes. The dataset, its annotations, and implementation codes will be released upon publication of the paper.

Nature has always proved to be a significant reservoir of bioactive scaffolds that have been used for the discovery of drugs since times. Medicinal plants continue to be a solid niche for biologically active and therapeutically effective chemical entities, opening up new avenues for the successful treatment of several human diseases. The contribution of plant-derived compounds to drug discovery, either in their original or in the semi-synthetic derivative form, extends far back in time. This review aims to focus on the sources, biological, and pharmacological profile of a pharmacologically active plant-derived coumarin, osthole, which is an important component of numerous remedial plants such as Cnidium monnieri. Several studies have revealed that osthole possess pharmacological properties such as anticancer, antioxidant, anti-hyperglycemic, neuroprotective, and antiplatelet. Osthole has been reported to regulate various signaling pathways, which in turn modulate several apoptosis-related proteins, cell cycle regulators, protein kinases, transcriptional factors, cytokines, and growth receptors affiliated with inflammation, proliferation and several other ailments. Osthole is known to halt proliferation and metastasis of cancerous cells by arresting the cell cycle and inducing apoptosis. The data in this review paper supports the pharmacological potential of osthole but further experimentation, biosafety profiling and synergistic effects of this compound need to be focused by the researchers to understand the full spectrum of pharmacological potential of this therapeutically potent compound.

Pakistan currently ranks 154 out of 189 countries on the UNDP’s Human Development Index. In this paper, we use a ‘political settlements analysis’ to understand how the distribution of political, ec...

Neurodegeneration is a multifactorial process involved the different cytotoxic pathways that lead towards neuronal cell death. Alzheimer's disease (AD) is a persistent neurodegenerative disorder that normally has a steady onset yet later on it worsens. The documented evidence of AD neuropathology manifested the neuro-inflammation, increased reactive oxygen, nitrogen species and decreased antioxidant protective process; mitochondrial dysfunction as well as increased level of acetylcholinesterase activity. Moreover, enhanced action of proteins leads towards neural apoptosis which have a vital role in the degeneration of neurons. The inability of commercial therapeutic options to treat AD with targeting single mechanism leads the attraction towards organic drugs. Ellagic acid is a dimer of gallic acid, latest studies expressed that ellagic acid can initiate the numerous cell signaling transmission and decrease the progression of disorders, involved in the degeneration of neurons. The influential property of ellagic acid to protect the neurons in neurodegenerative disorders is due to its antioxidant effect, iron chelating and mitochondrial protective effect. The main goal of this review is to critically analyze the molecular mode of action of ellagic acid against neurodegeneration.

The present study aimed to design and evaluate controlled porosity osmotic pump (CPOP) tablets of enalapril maleate (ENP) being used for the treatment of hypertension. D-optimal response surface design was used, considering cellulose acetate and osmotic agents (lactose and fructose) as variables while physicochemical parameters of tablets were taken as responses. The asymmetric, leachable membrane of cellulose acetate on ENP tablets was applied and an increase in the thickness of core tablets from 5 ± 0.01 to 5.4 ± 0.17 mm was observed. The average weight of all CPOP formulations ranged from 376.7 ± 0.4 to 389.1 ± 0.3 mg and hardness was 6.2 ± 0.02 to 6.32 ± 0.06 Kg/cm2. The friability of all formulations was less than 1%. 89.53 ± 1.05% of ENP release was observed in phosphate buffer pH 6.8 after 12 h. Due to the smallest AIC (Akaike information criteria) and the greatest r2 values, zero-order release kinetics model with non-Fickian diffusion behavior was observed in all proposed formulations. f1 (difference factor) values were 1.28 ± 0.06 to 12.64 ± 0.41% and f2 (similarity factor) values were 59.75 ± 0.24 to 94.03 ± 1.36% in the same dissolution medium. pH-independent behavior was observed in pH-responsive study. Dissolution efficiency (DE) ranged from 51.49 ± 0.23 to 53.52 ± 0.52% and mean dissolution time (MDT) values ranged from 5.27 ± 0.05 to 5.59 ± 0.23 h. No interaction between the ingredients was found in FTIR analysis. The optimized formulation with improved drug release property was found stable in the accelerated stability study of six months. CPOP tablets of ENP can be considered as an effective substitute for immediate-release tablets to control hypertension in chronic conditions.

Objective:To evaluate post-operative pain, recovery time and standard of living in patients undergoing LVHR in detail. Study design and Setting: This prospective cohort study was conducted at a tertiary care hospital of Karachi, Pakistan,after getting approval from the “National Medical Centre EthicalReview Board”, from January 2011 to December 2019, Methodology: Total n= 577 patients undergoing standard LVHR procedure (defect closed with non-absorbable monofilamentsuture, reinforced with intra-abdominal dual layer mesh, anchored with non-absorbable tacks & sutures). Patient demographics,perioperative & postoperative findings and post-operative pain analysis were investigated and presented as descriptivestatistics. Follow-up was carried out at 1stweek, 2ndweek, 3rdmonthly, 6 monthly and 12 monthly post-operative appointments. Results: During the study period of nine years (January 2011 to December 2019), 577 patients (primary ventral hernia n=232, recurrent ventral hernian=188 patients, incisional hernian=157) underwent LVHR. Mean post-operative hospitalstay was 1.53 ± 1.8 days. Mean post-operative pain assessment onvisual analog scale (VAS) after surgery (0-3days) wasreported to be 38.5±29 by 65 patients out of 577 (11.26%), which significantly decreased at the end of 1st week to 27.9 ± 25.6. Only 3 patients (0.51%) reported chronic pain during the span of 3-6 months. Conclusion: LVHR was associated with considerably less post-operative pain, shorter hospital stay and reduced time of convalescence. It is demonstrated that LVHR to be a safe and superior approach for the repair ventral hernias

Introduction: The spleen is located in the upper part of the abdominal cavity. As an organ, the spleen can have various shapes and size. Material and methods: The human spleen was studied in 273 cadavers (154 men and 119 women) who did not have diseases of the spleen. The shape of the spleen was analyzed based on splenic index, Michels classification. Results: The most common shape of the spleen in men is the elongated one. It was encountered in 79 (51.3%) cases out of 154. In women, the most common shape was the intermediate. It was encountered in 51 (42.9%) of the 119 cases. Based on Michels classification the clinoid (wedge) shape was encountered in 102 (37.74%) cases, triangular in 59 (21.83%) and tetrahedral in 30 (11.1%). In 30.26% the shape of the spleen couldn’t be classified according to Michels classification. In 21 cases (7.77%) the spleen had a flat shape; in 27 (9.99%) – dome-shaped; in 1 case (0,37%) – Z-shape; in 18 (6.66%) – round shape; in 6 (2.22%) – irregular shape; in 2 (0.66%) - shape with a node in the hilum; in 1 (0,37%) – rhomboid shape, in 2 (0,74%) – bilobed shape and in 4 cases (1,48%) – lobular shape. The splenic fissures located on the upper edge of the organ were found in 81 (29.91%) cases, and also on the lower edge - in 41 (14.02%) cases. In 13 (4.67%) cases fissures were encountered on both sides. In 148 (51.4%) cases the spleen had no fissures on its surface. Conclusions: The spleen has various shapes beyond the classical wedge, triangular and tetrahedral. All of these shapes do not represent a pathological finding but in certain situation may require further analysis and interpretation depending on the imaging technique and experience of the physician.

Background: The increased incidence of cholelithiasis and tumoral lesions of the hepatopancreatoduodenal zone leads to an increase in the number of patients with obstructive cholestasis. Aims: To identify the spectrum of pathological conditions developing after decompression of the biliary tract in obstructive cholestasis and to develop an effective pathogenetically determined algorithm for treating patients. Methods: The results of the examination and treatment of 216 patients with obstructive cholestasis, who underwent various options for decompression of the biliary tract, were analyzed. Obstructive cholestasis of a tumor genesis was present in 112 (51.8%) patients, benign cholestasis in 104 (48.2%). The main group included 112 patients, the comparison group included 104 patients. A two-stage tactics was applied in 133 (61.6%) cases, 83 patients (38.4%) were operated in one stage. The treatment results were compared for the experimental group (n=112) in which a pathogenetically based algorithm was applied and for the control group (n=104) receiving a standard therapy. Results: Accelerated decompression syndrome developed in 31 (14.3%) cases, of those 26 in the comparison group, 5 in the main group. Disorders of the water and electrolyte balance occurred in 32 (46.4%) patients with complete external bile diversion. Digestion remodeling syndrome was present in 44 patients from 117 patients with external bile diversion. Conclusions: It has been shown that the pathogenetically based therapy after biliary decompression significantly reduces the number of complications in the postoperative period.

Oroxylum indicumalso known as ‘pucukbeko’ in Malaysia is often consumed as raw salad (ulam) due to the belief that the plant has numerous therapeutics activities that could improve health. Despite its medicinal potential,however, there has been very limited data on the plant’s safety and toxicity profile particularly for long term consumption. More depth insight and evidence-based studies are needed to verify its safety as a potential herb. Therefore, this study aims to investigate sub acute oral toxicity of ethanol extract of O. indicum in C57BL/6 male mice. Twenty-five mice (n=5) were orally administered at single dose of normal saline (control), vehicle (5% DMSO), extracts (100, 200 and 500 mg/kg bw), respectively in accordance with OECD Guideline 420 for 28 days. Liver, kidneys, heart, lungs, testes, spleen,and blood samples were collected to determine the effects of the extract on the relative organ weight, tissue changes, and blood profile alterations in the end of the study. The sub-acute toxicity results demonstrated no lethal effects and abnormal behavioural changes in mice treated with an expansion dose up to a maximum of 500 mg/kg. No significant (p>0.05) changes in body weights, relative organ weight and haematological evaluation. Nevertheless, there were significant differences (p

OBJECTIVES Tramadol, an atypical opioid, is clinically efficacious in treating moderate to severe pain. The aim of current study was to find out the toxicological effects of tramadol exposure to pregnant rats and fetuses during the late phase of pregnancy. METHODS Wistar pregnant rats were exposed to 1.25, 2.5, or 5 mg/kg/day tramadol from 14th to 20th day of pregnancy. The same therapy was given to nonpregnant rats for 7 days. The body weight, oral glucose and lipid tolerance tests, and effect on complete blood parameters in both pregnant and nonpregnant rats were determined. On 20th day, maternal placentas were excised and weighed while fetuses were observed for any deformity and growth retardation. Oxidative stress biomarkers were estimated in the liver and kidney tissue homogenates of the pregnant and nonpregnant rats while the whole fetus homogenate was processed for the same. Moreover, histopathology of the liver and kidney of pregnant and nonpregnant rats were carried out. RESULTS Tramadol administration did not significantly alter the area under curve of the blood glucose and triglyceride levels in both the pregnant and nonpregnant rats. It reduced the live fetuses, placental weights, fetal length, and fetal weights. Tramadol treated pregnant rats showed significantly (p

Tobacco (Nicotiana tabacum) is an herbaceous plant originating from South America and processed into cigarettes for consumption. Polyphenols are considered vital components of tobacco in view of their contribution to antioxidant properties. This study aimed to determine the phenolic compounds in different tobacco varieties by applying cold extraction with methanol and distilled water. The extracts were screened for phenolic compound diversity and distribution as well as their antioxidant potential in different tobacco varieties. The results showed that the methanolic extract of tobacco SP-28 exhibited the highest value in the total phenolic content (24.82 ± 0.07 mg GAE/gd.w.) and total flavonoid content (4.42 ± 0.01 mg QE/gd.w.), while the water extract of tobacco SN-2 exhibited the highest value in the total condensed tannin (1.12 ± 0.03 mg CE/gd.w.). The radical scavenging capacities of tobacco SP-28 were relatively high in DPPH (18.20 ± 0.01 mg AAE/gd.w.) and FRAP (3.02 ± 0.10 mg AAE/gd.w.), whereas the ABTS value was the highest in tobacco SN-2 (37.25 ± 0.03 mg AAE/gd.w.), and the total antioxidant capacity was the highest in tobacco SN-1 (7.43 ± 0.18 mg AAE/gd.w.). LC-ESI-QTOF-MS/MS identified a total of 49 phenolic compounds, including phenolic acids (14), flavonoids (30), and other polyphenols (5) in four different tobacco varieties. Tobacco SP-28 showed the highest number of phenolic compounds, especially enriched in flavones. Our study highlights the antioxidant potential of tobacco extracts and reveals the phenolic distribution among different tobacco varieties that could support tobacco utilization in different pharmaceutical industries.

Pathogenic bacteria are the type of bacteria that is harmful to humans and can cause several diseases such as lung diseases, cholera, tuberculosis and syphilis. The multidrug-resistant bacteria that isolated from the patients were Klebsiella spp., Escherichia coli, Pseudomonas aeruginosa, that are known as the human pathogenic bacteria. The antibiotics that have been used against these bacteria were Meropenem MEM, Imipenem IPM, Gentamicin GNT, Co-AmoxiclavAMC and Ceftriaxone CRO. For the vial antibiotics, two different concentrations were prepared and Mueller Hinton agar used as the culture media. Pseudomonas aeruginosa was resistant against all vial and disk antibiotics. Escherichia coli was susceptible against all vial drugs and disks except ceftriaxone 10 mcg. Klebsiella spp. was susceptible against all vial and disk antibiotics. However, it was resistant against Ceftriaxone 10 mcg disk and Gentamicin 10 mcg. The most effective drug against all bacteria was Meropenem vial and disk. The most resistant bacteria against all antibiotic disks was Pseudomonas aeruginosa.

ObjectivesGiven the importance of continued COVID-19 surveillance, our objective was to present findings from a short follow-up survey of workforce SARS-CoV-2 antibody testing in previously seropositive participants and describe associations between work locations and negative seroconversion.MethodsWe conducted a follow-up cross-sectional survey on previously seropositive healthcare workers, using questionnaires and serology testing. Eligible employees previously consented to be contacted were invited by email to participate in a survey and laboratory blood draws. SAS V.9.4 was used to describe employee characteristics and seroconversion status. Binomial regression models were used to calculate unadjusted and adjusted prevalence ratios (PRs) of seronegativity. The multivariable analyses included age, gender, race/ethnicity, region of residence, work location, prior diagnosis/PCR results and days between antibody tests. Unadjusted and adjusted PRs 95% CIs and p values were reported.ResultsOf the 3990 employees emailed in the follow-up, 1631 completed an exposure survey and generated a blood-draw requisition form. Average time between serology testing was 4 months. Of the 955 employees with complete serology results, 79.1% were female, 53.4% were white and 46.4% resided in Long Island; 176 participants seroconverted to negative. In multivariable regression analyses adjusted for gender, race/ethnicity and region of residence, younger employees (Conclusions and relevancePatterns of negative seroconversion showed significant differences by sociodemographic and workplace characteristics. These results contribute information to workplace serosurveillance.

The flare-up in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that emerged in December 2019 in Wuhan, China, and spread expeditiously worldwide has become a health challenge globally. The rapid transmission, absence of anti-SARS-CoV-2 drugs, and inexistence of vaccine are further exacerbating the situation. Several drugs, including chloroquine, remdesivir, and favipiravir, are presently undergoing clinical investigation to further scrutinize their effectiveness and validity in the management of COVID-19. Natural products (NPs) in general, and plants constituents specifically, are unique sources for various effective and novel drugs. Immunostimulants, including vitamins, iron, zinc, chrysin, caffeic acid, and gallic acid, act as potent weapons against COVID-19 by reinvigorating the defensive mechanisms of the immune system. Immunity boosters prevent COVID-19 by stimulating the proliferation of T-cells, B-cells, and neutrophils, neutralizing the free radicals, inhibiting the immunosuppressive agents, and promoting cytokine production. Presently, antiviral therapy includes several lead compounds, such as baicalin, glycyrrhizin, theaflavin, and herbacetin, all of which seem to act against SARS-CoV-2 via particular targets, such as blocking virus entry, attachment to host cell receptor, inhibiting viral replication, and assembly and release.

The development of floating tablets with required buoyancy, lag time, and controlling release behaviour of drugs at target site is truly interesting and challenging task for researchers. Current study is concerned with the designing of effervescent floating controlled release tablets of clarithromycin and famotidine to treat peptic ulcer due to Helicobacter pylori (H. pylori) infection. Five formulations (F1-F5) were prepared, among which three formulations were of bilayered tablets while the remaining were included as plain tablets. These tablets were prepared by direct compression method using hydroxypropyl methylcellulose (HPMC) K100M, HPMC K4M and sodium bicarbonate as swelling and floating agents respectively. The qualitative tests such as thickness, hardness, weight variation, friability and uniformity of content were performed to ensure the quality of prepared tablets. The floating lag time of all formulations ranged from 14 to 20 seconds. The effervescent floating tablets with HPMC K4M (F1, F3 & F5) attained the total floating time of more than 12 hours, while tablets prepared with HPMC K100M (F2 & F4) achieved the total floating time of less than 7 hours. This difference in floating behaviour could be due to the variation in compaction and flow properties of the two polymers. The formulations with HPMC K100M (F2 & F4) have comparatively more sustained drug release properties when compared to F1, F3 and F4 using HPMC K4M as swelling and floating polymers. This could be attributed to better compaction of HPMC K100M. The prepared tablets follow non-Fickian diffusion kinetics. Overall, these floating controlled release effervescent bilayer and plain tablets may enhance the compliance and therapeutic outcomes of clarithromycin and famotidine in treatment of H. pylori.

Initial reports of a clinical response in patients treated with the radioligand [177Lu]-PSMA-617 for castration-resistant prostate cancer (CRPC) are promising, despite known inter- and intrapatient heterogeneity. In metastatic CRPC, we examined the association of baseline immunohistochemical (IHC) expression of prostate-specific membrane antigen (PSMA) in a single lesion and responsiveness to [177Lu]-PSMA-617 therapy, measured as the PSMA maximum standardized uptake value (SUVmax). Between 2015 and 2020, 19 patients with multiple metastases underwent single-lesion biopsy, [68Ga]-PSMA positron emission tomography (PET) imaging, and treatment with [177Lu]-PSMA-617. A monoclonal anti-PSMA antibody was used to semiquantitatively assess PSMA IHC in the biopsy specimen. Imaging evaluation of the biopsied single lesion and overall response was performed according to Positron Emission Tomography Response Criteria in Solid Tumors. The PSMA IHC histoscore correlated positively with pretreatment same-site PSMA SUVmax (rs = 0.6). Nine patients had imaging after three cycles of [177Lu]-PSMA-617 and were included in the lesion-specific analysis. Of these, five patients (55.6%) had an SUVmax response at the biopsy site, but three experienced overall progression. The histoscore was unable to predict the lesion-specific change in SUVmax (95% confidence interval [CI] −44.2 to 69.2) or PSA (95% CI−125.2 to 17.2). There was no correlation between single-lesion SUVmax and overall progression (rs = 0.1) on [68Ga]-PSMA PET imaging. Additional studies need to interrogate the clinical consequence of PSMA expression heterogeneity in metastases and the association with response to [177Lu]-PSMA-671. Patient summary Treatment with a radioactive binding molecule called [177Lu]-PSMA-617 for men with prostate cancer resistant to castration (CRPC) is showing promise. We investigated the association between the presence of PSMA protein in metastatic lesions at biopsy and response to [177Lu]-PSMA-617 among men with metastatic CRPC. We found that assessment of PSMA presence at biopsy is not a reliable predictor of response to [177Lu]-PSMA-617. Additional studies are needed to better determine which CRPC metastatic sites will respond to this therapy.

Aim: of this study is to correlate between point shear wave elastography(pSWE) and liver function tests (LFTs) to predict liver fibrosis in patients with non-alcoholic fatty liver disease (NAFLD). Materials and methods: this study is a cross sectional study conducted in Ultrasound Clinic in Suleymaniya city. The duration of the study was through the period from 1st of November, 2018 to 30th of June, 2019 on 50 NAFLD patients. After confirming NAFLD diagnosis, the patients were referred to Ultrasound Clinic to complete Point Shear Wave Elastography (PSWE). Results: showed a mean PSWE of NAFLD patient was 4.12±0.87 Kpa; 18% of them had high PSWE (> 4.6). Elastography fibrosis score was distributed to F0 (82%), F1 (6%), F2 (8%) and F3 (4%). The Aspartate Aminotransferase Platelet Ratio Index (APRI) fibrosis scores were distributed to F0 (48%), F1-3 (48%) and F4 (4%), There was a highly significant association between elastography fibrosis score and APRI fibrosis score of NAFLD patients (p

Peripheral nerve injuries are among those complicated medical conditions, which are still waiting for their highly effective first‐line therapies. In this study, the role of Calotropis procera crude leaves was evaluated at different doses for their effectiveness in improving functional recovery following sciatic nerve injury‐induced in the mouse model. Thirty‐two healthy albino mice were divided into four groups as Normal chow group (control, n = 8) and C. procera chow groups (50 mg/kg (n = 8), 100 mg/kg (n = 8) and 200 mg/kg (n = 8)). Behavioral analyses were performed to assess and compare improved functional recovery along with skeletal muscle mass measurement in all groups. Serum samples were analyzed for oxidative stress markers. Results showed that C. procera leaves at dose‐dependent manner showed statistically prominent (p, Role of Calotropis procera crude leaves was evaluated at different doses for their effectiveness in improving functional recovery following sciatic nerve injury‐induced in the mouse model.

Objectives Cardiac arrest and subsequent resuscitation have been shown to deplete plasma phospholipids. This depletion of phospholipids in circulating plasma may contribute to organ damage postresuscitation. Our aim was to identify the diminishment of essential phospholipids in postresuscitation plasma and develop a novel therapeutic approach of supplementing these depleted phospholipids that are required to prevent organ dysfunction postcardiac arrest, which may lead to improved survival. Design Clinical case control study followed by translational laboratory study. Setting Research institution. Patients/subjects Adult cardiac arrest patients and male Sprague-Dawley rats. Interventions Resuscitated rats after 10-minute asphyxial cardiac arrest were randomized to be treated with lysophosphatidylcholine specie or vehicle. Measurements and main results We first performed a phospholipid survey on human cardiac arrest and control plasma. Using mass spectrometry analysis followed by multivariable regression analyses, we found that plasma lysophosphatidylcholine levels were an independent discriminator of cardiac arrest. We also found that decreased plasma lysophosphatidylcholine was associated with poor patient outcomes. A similar association was observed in our rat model, with significantly greater depletion of plasma lysophosphatidylcholine with increased cardiac arrest time, suggesting an association of lysophosphatidylcholine levels with injury severity. Using a 10-minute cardiac arrest rat model, we tested supplementation of depleted lysophosphatidylcholine species, lysophosphatidylcholine(18:1), and lysophosphatidylcholine(22:6), which resulted in significantly increased survival compared with control. Furthermore, the survived rats treated with these lysophosphatidylcholine species exhibited significantly improved brain function. However, supplementing lysophosphatidylcholine(18:0), which did not decrease in the plasma after 10-minute cardiac arrest, had no beneficial effect. Conclusions Our data suggest that decreased plasma lysophosphatidylcholine is a major contributor to mortality and brain damage postcardiac arrest, and its supplementation may be a novel therapeutic approach.

Wildfires have an important role in the ecological process affecting ecosystems at multiple spatial scales. MCD64A1 500 m burned area product is used in this study to document trends of fire events from 2001 to 2019. The research aims to analyze the trend of burned areas in the country. Iraq is selected as study area of the research because of dramatically increasing the number of fires in the country. The study found that the lowest amount of burned areas were located in the center and southwest, while northeast and north faced most of the fires. The trend of burned areas in Iraq was an increase of 71.7 km2 per year, and, principally, in the last years, burned areas increased by 1363 km2. The most extensive burning areas occurred in the Ninawa Governorate (29%). In 2019, burned areas increased to around eight times compared to the yearly average. During 2019, one of the highest classes which contain burned area is “Cropland, rainfed” with 4366 km2 burned. High maximum air temperature and wind speed are the main factors that contribute to increasing burned areas; however, high precipitation and air pressure lead to a reducing amount of burned areas. The rapid increase of fires in the country as a result of burn crop field residues will lead to worsening air pollution and likely decrease forest area in the future.

Objective: To determine the effect of obestatin administration on FSH, LH, testosterone, leptin and MDA levels in obese Sprague Dawley Rats. Study Design: Laboratory based animal study. Place and Duration of Study: Physiology department, Army Medical College Rawalpindi, from Mar to Jun 2015. Methodology: This randomized controlled trial was conducted at Physiology Department Army medical college. Male healthy Sprague Dawley rats were randomly divided into 3 groups (n–15 each) i.e. control group (group I) fed with normal pellet diet (NPD), obese group (group II) and obestatin treated obese group (group III) fed with high fat diet (HFD). After 10 weeks, group III was treated with obestatin (1nmol/100ml intraperitoneally). Blood samples were obtained by terminal intracardiac sampling for bioasssays of FSH, LH, testosterone, leptin and MDA by ELISA. Results: Obestatin supplementation in obese rats showed significant increase in LH levels (3.79 ± 0.05) and testosterone levels (2.07 ± 0.22) when compared to the non treated obese rats (2.19 ± 0.07) and (1.37 ± 0.15) respectively while significant decrease in leptin (3.85 ± 0.23) and MDA levels (1.62 ± 0.07) was observed when compared to the non-treated control groups (6.10 ± 1.18) and (1.95 ± 0.07) respectively. However, serum FSH levels remained unchanged among the treated and nontreated groups. Conclusion: Obestatin increases the testosterone levels by augmenting the pituitary gonadal axis through decrease in the oxidative stress and leptin levels in obese rats.

The anatomy of the first vertebra, namely atlas, has significant clinical implications. Atlas is situated between the occipital bone and the second cervical vertebra (axis) and is one of the main points of head movement. Most congenital anomalies of the vertebra are diagnosed incidentally during imaging investigations and can be associated with cervical spine anomalies. The neurological symptoms may include weakness in the four limbs, acute neurologic deficits such as transient quadriparesis, paraparesis, Lhermitte's sign, chronic neck pain, and headache. This anomaly is also commonly seen in gonadal dysgenesis, Klippel-Feil syndrome, Arnold-Chiari malformations, and Turner and Down syndrome. Unlike other variations, which arise due to disturbances of ossification posterior midline clefts of the atlas, are different since they are a developmental failure of chondrogenesis. We therefore present an anatomical case and analysis of the literature about posterior arch clefts of atlas., {"references":["Covantev S, Mazuruc N, Belic O. Kimmerle Anomaly – An Important Anatomical Variation. Online J Health Allied Scs. 2018;17(3):8.","Pacheco Fernandes RM, Sarmento Pires LA, Martins Manaia JH, Cisne de Paula R, Babinski MA. Agenesis of the posterior arch of the atlas: an incidental finding in a polytraumatized patient. Coluna/Columna. 2019;18:81-3. doi: 10.1590/S1808-185120191801187278.","Kwon JK, Kim MS, Lee GJ. The incidence and clinical implications of congenital defects of atlantal arch. J Korean Neurosurg Soc. 2009;46(6):522-7. doi: 10.3340/jkns.2009.46.6.522.","Prempe RC, Gibson JC, Bhattacharya JJ. Mid-line clefts of the atlas: a diagnostic dilemma. Spinal Cord. 2002;40(2):92-3. doi: 10.1038/sj.sc.3101230.","Jefferson G. Fracture of the atlas vertebra. Report of four cases, and a review of those previously recorded. Br J Surg. 1919;7(27):407-22. doi: 10.1002/bjs.1800072713.","Currarino G, Rollins N, Diehl JT. Congenital defects of the posterior arch of the atlas: a report of seven cases including an affected mother and son. AJNR Am J Neuroradiol. 1994;15(2):249-54.","Geipel P. [Studies on the fissure formation of the atlas and epistropheus. IV]. Zentralbl Allg Pathol. 1955;94(1-2):19-84.","Schulze PJ, Buurman R. Absence of the posterior arch of the atlas. AJR Am J Roentgenol. 1980;134(1):178-80. doi: 10.2214/ajr.134.1.178.","Sabuncuoglu H, Ozdogan S, Karadag D, Kaynak ET. Congenital hypoplasia of the posterior arch of the atlas: case report and extensive review of the literature. Turk Neurosurg. 2011;21(1):97-103.","Hadley MN, Dickman CA, Browner CM, Sonntag VK. Acute traumatic atlas fractures: management and long term outcome. Neurosurgery. 1988;23(1):31-5. doi: 10.1227/00006123-198807000-00007.","Gehweiler JA Jr, Daffner RH, Roberts L Jr. Malformations of the atlas vertebra simulating the Jefferson fracture. AJR Am J Roentgenol. 1983;140(6):1083-6. doi: 10.2214/ajr.140.6.1083.","Chambers AA, Gaskill MF. Midline anterior atlas clefts: CT findings. J Comput Assist Tomogr. 1992;16(6):868-70. doi: 10.1097/00004728-199211000-00007.","Kumar R, Kalra SK, Vaid VK, Sahu RN, Mahapatra AK. Craniovertebral junction anomaly with atlas assimilation and reducible atlantoaxial dislocation: a rare constellation of bony abnormalities. Pediatr Neurosurg. 2008;44(5):402-5. doi: 10.1159/000149909.","Sharma A, Gaikwad SB, Deol PS, Mishra NK, Kale SS. Partial aplasia of the posterior arch of the atlas with an isolated posterior arch remnant: findings in three cases. AJNR Am J Neuroradiol. 2000;21(6):1167-71.","Sagiuchi T, Tachibana S, Sato K, Shimizu S, Kobayashi I, Oka H, et al. Lhermitte sign during yawning associated with congenital partial aplasia of the posterior arch of the atlas. AJNR Am J Neuroradiol. 2006;27(2):258-60.","Connor SE, Chandler C, Robinson S, Jarosz JM. Congenital midline cleft of the posterior arch of atlas: a rare cause of symptomatic cervical canal stenosis. Eur Radiol. 2001;11(9):1766-9. doi: 10.1007/s003300000755.","Devi BI, Shenoy SN, Panigrahi MK, Chandramouli BA, Das BS, Jayakumar PN. Anomaly of arch of atlas--a rare cause of symptomatic canal stenosis in children. Pediatr Neurosurg. 1997;26(4):214-7; discussion 217-8. doi: 10.1159/000121194.","Hegazy A. Clinical embryology for medical students and postgraduate doctors. Lap Lambert Academic Publishing; 2014."]}

Plants are integral components of pig and poultry feed, and aside from their raw nutritive value, some phytochemicals contain bioactive compounds. The aim of the present paper is to review recent advances in the use of some phytochemicals in pig and poultry feed, focusing on the examples of isoquinoline alkaloids, polyphenol rich sugarcane extracts and superoxide dismutase-rich melon pulp extracts. As gut health is critical for efficient production, the review will focus on recent results modulating oxidative stress within the gastrointestinal tract and the potential mechanisms of action.

COVID-19 in-hospital morbidity and mortality in people living with HIV (PLWH) were compared to HIV-negative COVID-19 patients within a New York City metropolitan health system, the hardest hit region in the United States early in the pandemic. A total of 10,202 inpatients were diagnosed with COVID-19, of which 99 were PLWH. PLWH were younger (58.3 years (SD = 12.42) versus 64.32 years (SD = 16.77), p < 0.001) and had a higher prevalence of men (73.7% versus 57.9%, p = 0.002) and Blacks (43.4% versus 21.7%, p < 0.001) than the HIV-negative population. PLWH had a higher prevalence of malignancies (18% versus 7%, p = < 0.001), chronic liver disease (12% versus 3%, p < 0.001), and end-stage renal disease (11% versus 4%, p = 0.007). Use of a ventilator, admission to the ICU, and in-hospital mortality were not different. Of the 99 PLWH, 12 were virally unsuppressed and 9 had CD4% < 14. Two of the 12 virally unsuppressed patients and 4/9 patients with CD4% < 14 died. Ninety-one of the 99 PLWH were on treatment for HIV, and 5 of the 8 not on treatment died. Among PLWH with prior values, absolute CD4 count decreased an average of 192 cells/mm3 at the time of COVID-19 diagnosis ( p < 0.001). Hospitalized patients with HIV and COVID-19 coinfection did not have worse outcomes than the general population. Among PLWH, those with CD4%

Purpose. To systematically review the results of comparative studies of modern cataract surgery in pediatric uveitis with or without intraocular lens (IOL) implantation and to perform comparative meta-analyses to compare visual acuity outcomes and complication rates. Methods. On 12 November 2020, we systematically searched the Cochrane Central, PubMed/MEDLINE, EMBASE, ClinicalTrials.gov, and all affiliated databases of the Web of Science. Two authors independently reviewed studies and extracted data. Studies were reviewed qualitatively in text and quantitatively with meta-analyses. Outcome measures were preoperative and postoperative best-corrected visual acuity (BCVA), inflammation control, and rates of postoperative complications. Results. Ten studies of 288 eyes were eligible for review of which the majority were eyes with juvenile idiopathic arthritis-associated uveitis. Summary estimates revealed that the BCVA was better in pseudophakic eyes vs. aphakic eyes (1-year postoperative: −0.23 logMAR, 95% CI: −0.43 to −0.03 logMAR, P = 0.027 ; 5-year postoperative: −0.35 logMAR, 95% CI: −0.51 to −0.18 logMAR, P = 0.000036 ). Pseudophakic eyes had more visual axis opacification (OR 6.76, 95% CI: 2.73 to 16.8, P = 0.000036 ) and less hypotony (OR 0.19, 95% CI: 0.04 to 0.95, P = 0.044 ). Conclusions. In modern era cataract surgery on eyes with pediatric uveitis with IOL implantation leads to satisfactory and superior visual outcomes and no differences in complication rates apart from an increased prevalence of visual axis opacification and a decreased prevalence of hypotony when compared to aphakia. However, limitations of the retrospective design and the presence of selection bias necessitate a careful interpretation.

Background: Maxillofacial fractures are the most commonly reported injuries in developed as well as developing countries, among all facial bones; mandible is most commonly fractured. The pattern of mandibular bone fracture has changed drastically over the past two decades due to increase occurrence of high velocity impact. The objective of this study was to determine the pattern and causes of mandibular fractures that have reported in the Department of Surgery at Punjab Dental Hospital Lahore. Methods: Ethical Review Committee of de’Montmorency College of Dentistry (DCD), Lahore, granted the Ethical approval for this retrospective study. Data was taken from the Department of Oral and Maxillofacial Surgery of de’Montmorency College of Dentistry/ Punjab Dental Hospital (DCD/PDH) by using secondary data of indoor register from January 2017 to December 2020. Record which met our inclusion criteria was included in this study and record having incomplete data was excluded. A total of 1230 cases were entered in SPSS version 21 to determine descriptive statistic of the data. Percentages and frequencies of variables like gender, site of fracture and causes of fracture were calculated. Results: Our study included 1230 patients out of which 873 were males and 357 were females. The most affected age group was the fourth decade of life (38.1%) and the major etiological factor was road traffic accident (RTA) which led to fractures in 1067 patients (86.7%). Para-symphysis and symphysis was the most commonly affected area comprising of 36.2% of all fractures. The second most common sit was condyle (23.9%). Least commonly fractured site was coronoid process of the mandible. Conclusion: Cause of majority of mandible fractures is RTA and most commonly affected anatomical site were Para-symphysis and Symphysis.

Background Meropenem, a potent carbapenem is considered the first choice for the empirical treatment of severe infections. Being a hydrophilic drug, more than 83% of the administered dose is eliminated through the renal route, and therefore, the kidney status of the patient may have a significant effect on meropenem clearance (CL). Materials and methods The data of 205 samples obtained from 59 patients treated with meropenem at the General Hospital Lahore, Pakistan, was used for the development of a population pharmacokinetic (-popPK) model by using nonlinear mixed-effects modeling software. The effect of age, body weight, creatinine clearance (CRCL), and gender was observed on meropenem CL through a stepwise covariate modeling approach. Simulations of 1,000 mg q8h and 1,500 mg q12h over 3-hour infusion were performed based on the renal status of the patients. Results A two-compartment model was used for popPK analysis, and the values of the pharmacokinetic parameters for CL, V1, V2, and Q were 12.2 L/h, 21.7 L, 7.74 L, and 3.28 L/h, respectively. Meropenem CL was significantly influenced by CRCL, while no significant effect of body weight, age, and sex was observed. Both simulated dosage regimens were equally effective if CRCL of the patient was ≤ 100 mL/min, while 1,000 mg q8h produced better results if CRCL was > 100 mL/min. Conclusion The CL of meropenem depends on the renal status of the patients. The model can be used for dosing simulations based on the CRCL of the patients in order to tailor the dose of meropenem in Pakistani patients.

Background/aim Positron emission tomography/computed tomography (PET/CT) plays an important role in cancer localization in ectopic Cushing's syndrome (ECS). However, the choice of the optimal tracer for investigation of this disease is still unclear. We aimed to evaluate the diagnostic feasibility of [18F]fluoro-2-deoxyglucose ([18F]FDG), [18F]fluoro-L-dihydroxyphenylalanine ([18F] FDOPA), and [68Ga]-DOTA-1-Nal3-octreotide ([68Ga]-DOTANOC) in ECS. Patients and methods All PET/CT scans of patients admitted to our department for suspected ECS between 2010 and 2020 were retrospectively analysed. Results Collectively, 30 PET/CT examinations, 11 with [18F]FDOPA, 11 with [18F]FDG and 8 with [68Ga]GaDOTANOC were conducted for 18 patients eligible for analysis. [18F]FDG detected the tumour in 3/6 of the cases, [18F]FDOPA in 3/4, and [68Ga]GaDOTANOC in 3/3. [18F]FDOPA was the only tracer without false positive results. Conclusion [68Ga]GaDOTANOC and [18F]FDOPA showed superior results compared to [18F]FDG, although the sensitivity of the tracers might be influenced by the aetiology of the tumour underlying the ECS.

A natural product such as chitosan promotes health benefits and extends the shelf life of the processed products. Chitosan has been used as a food additive due to its antioxidant and antimicrobial activities. This study was conducted to optimize the chitosan concentration as a coating agent on the quality and shelf life of Labeo rohita fillets during frozen storage. Chitosan (CH) solutions were prepared with 0.5 %, 1 %, and 2 % (w/v) CH in 1 % (v/v) glacial acetic acid for coating application. The control (0% CH) and CH treated fish fillets were stored at -18 °C for 14 weeks and assessed for chemical (pH, thiobarbituric acid reactive substances (TBARS), total volatile basic nitrogen (TVB-N), and K-value), microbiological (aerobic plate count (APC)), and sensory properties. The pH, TBARS, and K-value of 1 % and 2 % CH treated fish fillets were acceptable up to 14th week of storage, while TVB-N value was permissible up to 12th week of storage. After 14th week of storage, the APC of control, 0.5 %, 1 %, and 2 % CH treated fillets were 7.18 log CFU/g, 5.02 log CFU/g, 4.13 log CFU/g, and 3.21 log CFU/g, respectively. The fish fillets treated with 1 % and 2 % CH had acceptable sensory attributes up to 12th week, while control fillets were unacceptable after the 6th week of storage. This study demonstrated that 1% CH could be used as a natural additive for keeping the quality and extending the shelf life of L. rohita fillets during frozen storage.

A series of novel theophylline-7-acetic acid (acefylline)-derived 1,2,4-triazole hybrids with N-phenyl acetamide moieties (11a–j) have been synthesized and tested for their inhibitory (in vitro) potential against two cancer cell lines, A549 (lung) and MCF-7 (breast), using MTT assay. Among these derivatives, 11a, 11c, 11d, 11g, and 11h displayed remarkable activity against both cancer cell lines having cell viability values in the 21.74 ± 1.60–55.37 ± 4.60% range compared to acefylline (86.32 ± 1.75%) using 100 μg/μL concentration of compounds. These compounds were further screened against the A549 cancer cell line (lung) to find their half-maximal inhibitory concentration (IC50) by applying various concentrations of these compounds. Compound 11g (2-(5-((1,3-dimethyl-2,6-dioxo-2,3-dihydro-1H-purin-7(6H)-yl)methyl)-4-phenyl-4H-1,2,4-triazol-3-ylthio)-N-p-tolylacetamide) with the least IC50 value (1.25 ± 1.36 μM) was discerned as a strong inhibitor of cancer cell multiplication in both cell lines (A549 and MCF-7). Their hemolytic studies revealed that all of them had very low cytotoxicity. Finally, in silico modeling was carried out to find the mode of binding of the highly active compound (11g), which was according to the results of anti-cancer activity.

The purpose of this study was to examine the progression of discourse on race within leisure studies scholarship through the lens of racecraft and the construct of mattering. The Journal of Leisure Research as well as Schole were examined within the periods of the 1990s (1989–2000) and the 2010s (2009–2019). Articles were chosen based upon their employment of the keywords of community recreation, youth development, and race within both time periods, yielding a total of 99 articles that were examined. A discourse historical approach (DHA) was utilized to assess the impact of the socio-political context on leisure research as well as the development of discourse on race. Through DHA techniques and the concept of racecraft, this study classified articles under five overarching themes: Faint mentions of race, racialization in the negative, improper terminology use, intentionality of race, and inadequate lens of problem/solution. Based upon the findings, leisure literature has displayed minimal progression in its conceptualizations of race. Leisure studies scholarship reflects the dominant discourse through its latent ideology of racism that maintains marginalization of various racialized ethnic groups. It is posited that, without institutional examination and targeted mitigation efforts, the field of leisure will continue to uphold a detrimental racial order with an underdeveloped political and historical stance on race.

Recent calls for papers in numerous academic journals within leisure studies have focused on a global and nation-specific climate that leans towards autocratic policy development, fascist rhetoric ...

Background The European Atherosclerosis Society Familial Hypercholesterolaemia Studies Collaboration (FHSC) global registry provides a platform for the global surveillance of familial hypercholesterolaemia through harmonisation and pooling of multinational data. In this study, we aimed to characterise the adult population with heterozygous familial hypercholesterolaemia and described how it is detected and managed globally. Methods Using FHSC global registry data, we did a cross-sectional assessment of adults (aged 18 years or older) with a clinical or genetic diagnosis of probable or definite heterozygous familial hypercholesterolaemia at the time they were entered into the registries. Data were assessed overall and by WHO regions, sex, and index versus non-index cases. Findings Of the 61 612 individuals in the registry, 42 167 adults (21 999 [53.6%] women) from 56 countries were included in the study. Of these, 31 798 (75.4%) were diagnosed with the Dutch Lipid Clinic Network criteria, and 35 490 (84.2%) were from the WHO region of Europe. Median age of participants at entry in the registry was 46.2 years (IQR 34.3-58.0); median age at diagnosis of familial hypercholesterolaemia was 44.4 years (32.5-56.5), with 40.2% of participants younger than 40 years when diagnosed. Prevalence of cardiovascular risk factors increased progressively with age and varied by WHO region. Prevalence of coronary disease was 17.4% (2.1% for stroke and 5.2% for peripheral artery disease), increasing with concentrations of untreated LDL cholesterol, and was about two times lower in women than in men. Among patients receiving lipid-lowering medications, 16 803 (81.1%) were receiving statins and 3691 (21.2%) were on combination therapy, with greater use of more potent lipid-lowering medication in men than in women. Median LDL cholesterol was 5.43 mmol/L (IQR 4.32-6.72) among patients not taking lipid-lowering medications and 4.23 mmol/L (3.20-5.66) among those taking them. Among patients taking lipid-lowering medications, 2.7% had LDL cholesterol lower than 1.8 mmol/L; the use of combination therapy, particularly with three drugs and with proprotein convertase subtilisin-kexin type 9 inhibitors, was associated with a higher proportion and greater odds of having LDL cholesterol lower than 1.8 mmol/L. Compared with index cases, patients who were non-index cases were younger, with lower LDL cholesterol and lower prevalence of cardiovascular risk factors and cardiovascular diseases (all p, Pfizer Independent Grant for Learning Change [16157823]; Amgen; Merck Sharp Dohme; Sanofi-Aventis; Daiichi Sankyo; Regeneron; National Institute for Health Research (NIHR) Imperial Biomedical Research Centre, UK; NIHR; Czech Ministry of Health [NU20-02-00261]; Canadian Institutes of Health Research; Austrian Heart Foundation; Tyrolean Regional Government; Gulf Heart Association, The EAS FHSC is an academic initiative that has received funding from a Pfizer Independent Grant for Learning & Change 2014 (16157823) and from investigator-initiated research grants to the European Atherosclerosis Society-Imperial College London from Amgen, Merck Sharp & Dohme, Sanofi-Aventis, Daiichi Sankyo, and Regeneron. KKR acknowledges support from the National Institute for Health Research (NIHR) Imperial Biomedical Research Centre, UK. KID acknowledges support from a PhD Studentship from NIHR under the Applied Health Research programme for Northwest London, UK (the views expressed in this publication are those of the authors and not necessarily those of the National Health Service, the NIHR, or the Department of Health). TF was supported by a grant from the Czech Ministry of Health (NU20-02-00261). JG receives support from the Canadian Institutes of Health Research. The Austrian Familial Hypercholesterolaemia registry has been supported by funds from the Austrian Heart Foundation and the Tyrolean Regional Government. The Gulf Familial Hypercholesterolaemia registry was done under the auspices of the Gulf Heart Association.

The N-methyl-D-aspartate receptor (NMDAR) plays a crucial role in neurodegenerative diseases such as Alzheimer’s disease and in the treatment of major depression by new fast-acting antidepressants such as ketamine. Given their broad implications, GluN2B-containing NMDARs have been of large interest as diagnostic and therapeutic targets. Recently, (R)-11C-Me-NB1 was investigated preclinically and shown to be a promising radioligand for imaging GluN2B subunits. Here, we report on the performance characteristics of this novel radioligand in a first-in-human PET study. Methods: Six healthy male subjects were scanned twice on a fully-integrated PET/MR scanner with (R)-11C-Me-NB1 for 120 min. Brain uptake and tracer distribution over time were investigated by standardized uptake values (SUV). Test-retest reliability was assessed with the absolute percentage difference (APD) and the coefficient of variation (COV). Exploratory total volumes of distribution (VT) were computed using an arterial input function and the Logan plot as well as a constrained two-tissue compartment model with K1/k2 coupled (2TCM). SUV was correlated with VT to investigate its potential as a surrogate marker of GluN2B expression. Results: High and heterogeneous radioligand uptake was observed across the entire gray matter with reversible kinetics within the scan time. SUV APD ranged from 6.8 - 8.5% and COV from 4.9 - 6.0%, indicating a high test-retest reliability. A moderate correlation was found between SUV averaged from 70-90 min and VT using Logan plot (Spearman’s rho = 0.44). Correlation between VT Logan and 2TCM was r= 0.76. Conclusion: The novel radioligand, (R)-11C-Me-NB1, was highly effective in mapping GluN2B-enriched NMDARs in the human brain. With a heterogeneous uptake and a high test-retest reliability, this radioligand offers promise to deepen our understanding of the GluN2B-containing NMDA receptor in the pathophysiology and treatment of neuropsychiatric disease such as Alzheimer’s disease and major depression. Additionally, it could help in the selection of appropriate doses of GluN2B-targeting drugs. ISSN:0097-9058 ISSN:0022-3123 ISSN:0161-5505 ISSN:2159-662X ISSN:1535-5667

Background: Malignant salivary gland tumors (MSGTs) consist of a heterogeneous group of neoplasms with complex clinicopathological features and biological behaviors. The purpose of this study was to determine the expression of Bcl-2 antiapoptotic protein in mucoepidermoid carcinoma (MEC), adenoid cystic carcinoma (ADCC), acinic cell carcinoma (ACC) and polymorphous low-grade adenocarcinoma (PLGA) of salivary glands and to find out its association with different grades of these tumors. Material and Methods: This descriptive study included 55 cases of MSGTs. Tissue sections were stained with routine hematoxylin and eosin stain as well as Bcl-2 immunostain. MSGTs were graded as low grade (Low grade MEC, ACC, PLGA, and tubular pattern of ADCC), intermediate grade (cribriform pattern of ADCC, and intermediate grade of MEC) and high grade (high grade of MEC and solid pattern of ADCC) tumors on H&E sections. Bcl-2 expression was scored as ‘negative’ (50% of neoplastic cells), respectively. Results: MSGTs most commonly involved the parotid gland (52.7%), while ADCC (40%) and MEC (38.2%) were the most common tumors. Expression of Bcl-2 was strongly positive in 56.4% cases of MSGTs which included ADCC (71%), MEC (19.4%) and ACC (9.7%), respectively. A significant association was found between Bcl-2 staining and types of MSGTs i.e., MEC, ADCC, ACC (P = .001) as well as between Bcl-2 staining and grades of MSGTs (P = .013). Conclusions: Bcl-2 protein is expressed in malignant salivary gland tumors. Its expression maybe helpful in grading small biopsies, predicting behavior, and planning targeted therapy of MSGTs.

The study was to compare efficacy of parenteral versus oral vitamin D replacement in hypovitaminosis. Study Design: Randomized trial. Setting: Medical Outpatient Clinics of Madinah Teaching Hospital, Chiniot General Hospital and Maqsooda Zia Hospital, Faisalabad. Period: 6 months (Oct 2017 – Apr 2018). Material & Methods: 84 patients were included in the study. Baseline 25(OH) D levels were determined, and followed-up at 3rd and 6th weeks following vitamin D replacement. After giving the first dose of vitamin D (parenteral or oral), patients were given maintenance dose of calcium and vitamin D supplement as per recommended daily allowance (RDA). Patients with significant clinical improvement were also noted in both groups. Results: The change in vitamin D level after 3 weeks and 6 weeks of replacement through oral route and intramuscular (IM) route was compared; which was found to be statistically significant in both groups (p value < 0.05). Mean change in vitamin D levels after 6 weeks of replacement in all the patients was 17.96 + 13.0. In oral group, it was 13.5 + 10.07 and in IM group, it was 22.40 + 14.18. This clearly shows that it was higher in the IM group compared to the oral group. This difference was statistically significant (p=0.001). The percentage change in the serum 25-OH D level was 53% and 79% for oral group compared to 103% and 207% for the IM group, y after 3 and 6 weeks of replacement respectively. Conclusion: While managing hypovitaminosis D, IM route of administration is more effective. There was significant improvement in the serum 25OHD levels in the IM group. A larger randomized control trial should be done comparing the efficacy of oral and IM route of vitamin D replacement.

The Intervertebral Disc (IVD) is a fibrocartilaginous tissue instrumental in spine flexibility, allowing for the bending and twisting motion between vertebral bodies. Degenerative Disc Disease (DDD) results from the complex and chronic deterioration in IVD organization, structure, and function

The current research aimed at designing mesoporous silica nanoparticles (MSNs) for a controlled coadministration of salicylic acid (SA) and ketoconazole (KCZ) to effectively treat highly resistant fungal infections. The sol-gel method was used to formulate MSNs, which were further optimized using central composite rotatable design (CCRD) by investigating mathematical impact of independent formulation variables such as pH, stirring time, and stirring speed on dependent variables entrapment efficiency (EE) and drug release. The selected optimized MSNs and pure drugs were subjected to comparative in vitro/in vivo antifungal studies, skin irritation, cytotoxicity, and histopathological evaluations. The obtained negatively charged (-23.1), free flowing spherical, highly porous structured MSNs having a size distribution of 300-500 nm were suggestive of high storage stability and improved cell proliferation due to enhanced oxygen supply to cells. The physico-chemical evaluation of SA/KCZ-loaded MSNs performed through powder X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), and thermal gravimetric analysis (TGA) indicates absolute lack of any interaction between formulation components and successful encapsulation of both drugs in MSNs. The EESA, EEKCZ, SA release, and KCZ release varied significantly from 34 to 89%, 36 to 85%, 39 to 88%, and 43 to 90%, respectively, indicating the quadratic impact of formulation variables on obtained MSNs. For MSNs, the skin tolerability and cell viability percentage rate were also having an extraordinary advantage over suspension of pure drugs. The optimized SA/KCZ-loaded MSNs demonstrated comparatively enhanced in vitro/in vivo antifungal activities and rapid wound healing efficacy in histopathological evaluation without any skin irritation impact, suggesting the MSNs potential for the simultaneous codelivery of antifungal and keratolyic agents in sustained release fashion.

Purpose: This study aimed to optimize the effective doses of mitomycin C, 5-fluorouracil, and their combination on cultivated basal cell carcinoma. Methods: Cultivated basal cell carcinoma and fibroblastic cells were treated with different concentrations of mitomycin C, 5-fluorouracil, and their combination. Cell viability, cell cycle, apoptosis, and expression levels of TP53, CDKN1A, and CDK6 were investigated. The most effective drug with its optimum dosage was administered via multiple intralesional injections to a 65-year-old woman with advanced periorbital nodulo-ulcerative BCC. Results: The concentrations of 0.00312 and 0.312 mg/mL were considered optimum for mitomycin C and 5-fluorouracil, respectively. The mean viabilities of basal cell carcinoma treated with mitomycin C alone and its combination with 5-fluorouracil were significantly less than those of the controls (p=0.002 and p=0.04, respectively). The cell cycle of all the treated basal cell carcinoma groups was arrested in the S phase. The apoptotic rates (p=0.002) of mitomycin C treated basal cell carcinoma were higher than those of the other treated cells, and their TP53 was significantly upregulated (p=0.0001). Moreover, CDKN1A was upregulated, whereas CDK6 was downregulated in basal cell carcinoma treated with either 5-fluorouracil (p=0.0001 and p=0.01, respectively) or the combination of 5-fluorouracil and mitomycin C (p=0.007 and p=0.001, respectively). Basal cell carcinoma lesions were significantly alleviated following mitomycin C injections in the reported patient. Conclusion: Our in vitro results revealed that the effective doses of mitomycin C and 5-fluorouracil on cultivated basal cell carcinoma were optimized. Mitomycin C was more effective in inducing the apoptosis of basal cell carcinoma than 5-fluorouracil and their combination. The intralesional injections of the optimum dose of mitomycin C could be proposed for the nonsurgical treatment of advanced eyelid basal cell carcinoma. RESUMO Objetivo: Otimizar a dose efetiva de mitomicina C, 5fluorouracil e da combinação de ambos em culturas de células de carcinoma basocelular (CBC). Métodos: Culturas de células de células de carcinoma basocelular e de fibroblastos foram tratadas com diferentes concentrações de mitomicina C, 5fluorouracil e combinação de ambos. Além disto, foram investigados a viabilidade celular, o ciclo celular, a apoptose e a expressão dos genes TP53, CDKN1A e CDK6. O medicamento mais eficaz, em sua dosagem otimizada, foi administrado em últiplas injeções intralesionais em uma mulher de 65 anos com carcinoma basocelular nódulo-ulcerativo periorbital avançado. Resultados: A concentração de 0,00312 mg/mL de mitomicina C e a de 0,312 mg/mL de 5fluorouracil foram consideradas as ideias. A viabilidade média das células de carcinoma basocelular tratadas com mitomicina C isoladamente e em combinação foi significativamente menor que nas células de controle (respectivamente, p=0,002 e p=0,04). Todos os grupos de carcinoma basocelular tratados demonstraram interrupção do ciclo celular na fase S. As células de carcinoma basocelular tratadas com mitomicina C mostraram maiores taxas de apoptose (p=0,002) e significativa regulação positiva do gene TP53 (p=0,0001). Além disso, o gene CDKN1A foi positivamente regulado e o gene CDK6 foi negativamente regulado em células de carcinoma basocelular tratadas com 5fluorouracil (respectivamente, p=0,0001 e p=0,01) ou com a combinação de medicamentos (respectivamente, p=0,007 e p=0,001). Injeções posteriores de mitomicina C na paciente em questão levaram à melhora significativa da lesão do carcinoma basocelular. Conclusão: Nossos resultados in vitro otimizaram as doses efetivas de mitomicina C e 5fluorouracil na cultura de células de carcinoma basocelular e mostraram que a mitomicina C tem mais eficácia na apoptose de células de carcinoma basocelular do que o 5fluorouracil e a combinação de ambos. Injeções intralesionais de doses otimizadas de mitomicina C podem ser propostas para o tratamento não cirúrgico do células de carcinoma basocelular avançado de pálpebra.

Prosopis farcta (Banks & Sol.) J.F.Macbr. is an emerging medicinal plant containing a diverse array of phytochemicals, including protein, fat, carbohydrate, fibre, alkaloids, fatty acids, glycosides, and polyphenols, with strong antioxidant potential. However, the screening and characterization of phenolic compounds in P. farcta is limited. This study is conducted to determine the polyphenol contents and their antioxidant activity in P. farcta leaves samples via liquid chromatography-electrospray ionization quadrupole time-of-flight mass spectrometry (LC-ESI-QTOF-MS/MS) and high-performance liquid chromatography-photodiode array (HPLC-PDA). Total phenolic content (TPC), total flavonoid content (TFC), and total tannins content (TTC) were determined for polyphenol estimation. The antioxidant properties were measured by total antioxidant capacity (TAC), 2,2'-Diphenyl-2-picrylhydrazyl (DPPH), Ferric Reducing Antioxidant Power (FRAP), and 2,2"²-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS). LC-ESI-QTOF-MS/MS was used to identify and characterize 47 phenolic compounds, which mainly included phenolic acids (13), flavonoids (28), other polyphenols (4), lignans (1), and stilbenes (1). According to HPLC-PDA quantification, chlorogenic acid (9.78 ± 2.15 mg/g dw) was the most abundant phenolic acid, while the main flavonoids included catechin (12.73 ± 1.29 mg/g dw) and kaempferol (7.93 ± 1.47 mg/g dw). The study demonstrated the significance of P. farcta as a rich source of phenolic compounds with antioxidant capacity that can be widely used in food, beverage, feed, and pharmaceutical applications.