Assessment of neuroprotective potential of Tualang honey in alzheimer model of rat

Reduction in cerebral blood flow (CBF) due to aging has been associated with neurodegenerative disorders including Alzheimer’s disease and dementia. Experimentally, a condition of chronic cerebral hypoperfusion due to reduced CBF can be induced by permanent bilateral occlusion of common carotid arteries (2-vessel occlusion, 2VO) in rats. Honey is a natural product that has been widely used since long time as a nutrient, for its therapeutic effects in traditional medicine, and recently as an antioxidant. Since oxidative stress leading to neuroinflammation, resulting in neuronal apoptosis and death, is one of the mechanisms which is thought to play a significant role in chronic degenerative neurological disorders, the present study was planned to assess the neuroprotective role of Honey in chronic cerebral hypoperfusion-induced neurodegeneration. After acclimatization, thirty Sprague Dawley rats weighing 200-250 g were equally divided into three groups. Group A – sham control, Group B – 2VO, and Group C – 2VO-H (treated daily with Honey (1.2 g/kg freshly diluted with distilled water, orally by 30 gavage every morning following 2VO). At 10th week, all the rats were euthanized and the hippocampi were isolated. Viable neuronal cell were count in the hippocampal CA-1 region. The results showed damaged, distorted, irregular cells with shrunken cytoplasm and dark pykonotic nuclei in 2VO rats as compared to sham control (p<0.001). Treatment of rats with honey restored the hippocampal cells to their normal structure and revealed the reduced loss of neurons in 2VO+H rats as compared to untreated 2VO rats (p<0.001). This study shows that Malaysian tualang honey might have therapeutic potential for the treatment of chronic cerebral hypoperfusion related neurodegenerative disorders including Alzheimer’s disease

Immunohistochemical and Molecular Features of Melanomas Exhibiting Intratumor and Intertumor Histomorphologic Heterogeneity

Melanoma is a heterogeneous neoplasm at the histomorphologic, immunophenotypic, and molecular levels. Melanoma with extreme histomorphologic heterogeneity can pose a diagnostic challenge in which the diagnosis may predominantly rely on its immunophenotypic profile. However, tumor survival and response to therapy are linked to tumor genetic heterogeneity rather than tumor morphology. Therefore, understating the molecular characteristics of such melanomas become indispensable. In this study, DNA was extracted from 11 morphologically distinct regions in eight formalin-fixed, paraffin-embedded melanomas. In each region, mutations in 50 cancer-related genes were tested using next-generation sequencing (NGS). A tumor was considered genetically heterogeneous if at least one non-overlapping mutation was identified either between the histologically distinct regions of the same tumor (intratumor heterogeneity) or among the histologically distinct regions of the paired primary and metastatic tumors within the same patient (intertumor heterogeneity). Our results revealed that genetic heterogeneity existed in all tumors as non-overlapping mutations were detected in every tested tumor (n = 5, 100%; intratumor: n = 2, 40%; intertumor: n = 3, 60%). Conversely, overlapping mutations were also detected in all the tested regions (n = 11, 100%). Melanomas exhibiting histomorphologic heterogeneity are often associated with genetic heterogeneity, which might contribute to tumor survival and poor response to therapy

Increased resting cerebral blood flow in adult Fabry disease: MRI arterial spin labeling study

OBJECTIVE: To assess resting cerebral blood flow (CBF) in the whole-brain and cerebral white matter (WM) and gray matter (GM) of adults with Fabry disease (FD), using arterial spin labeling (ASL) MRI, and to investigate CBF correlations with WM hyperintensity (WMH) volume and the circulating biomarker lyso-Gb3. METHODS: This cross-sectional, case-control study included 25 patients with genetically confirmed FD and 18 age-matched healthy controls. We quantified resting CBF using Quantitative Signal Targeting With Alternating Radiofrequency Labeling of Arterial Regions (QUASAR) ASL MRI. We measured WMH volume using semiautomated software. We measured CBF in regions of interest in whole-brain, WM, and deep GM, and assessed correlations with WMH volume and plasma lyso-Gb3. RESULTS: The mean age (% male) for FD and healthy controls was 42.2 years (44%) and 37.1 years (50%). Mean whole-brain CBF was 27.56 mL/100 mL/min (95% confidence interval [CI] 23.78-31.34) for FD vs 22.39 mL/100 mL/min (95% CI 20.08-24.70) for healthy controls, p = 0.03. In WM, CBF was higher in FD (22.42 mL/100 mL/min [95% CI 17.72-27.12] vs 16.25 mL/100 mL/min [95% CI 14.03-18.48], p = 0.05). In deep GM, CBF was similar between groups (40.41 mL/100 mL/min [95% CI 36.85-43.97] for FD vs 37.46 mL/100 mL/min [95% CI 32.57-42.35], p = 0.38). In patients with FD with WMH (n = 20), whole-brain CBF correlated with WMH volume (r = 0.59, p = 0.006), not with plasma lyso-Gb3. CONCLUSION: In FD, resting CBF is increased in WM but not deep GM. In FD, CBF correlates with WMH, suggesting that cerebral perfusion changes might contribute to, or result from, WM injury

Prognostic model for patient survival in primary anorectal mucosal melanoma:stage at presentation determines relevance of histopathologic features

Pathological staging of primary anorectal mucosal melanoma is often performed according to the American Joint Commission on Cancer (AJCC) guidelines for cutaneous melanoma, as an anorectal melanoma-specific staging system does not exist. However, it remains unknown whether prognostic factors derived for cutaneous melanoma also stratify risk in anorectal melanoma. We retrospectively determined correlations between clinicopathological parameters and disease-specific survival in 160 patients. Patients were grouped by clinical stage at presentation (localized disease, regional or distant metastases). Cox proportional hazards regression models determined associations with disease-specific survival. We also summarized the somatic mutations identified in a subset of tumors analyzed for hotspot mutations in cancer-associated gene panels. Most of the patients were white (82%) and female (61%). The median age was 62 years. With a median follow-up of 1.63 years, median disease-specific survival was 1.75 years, and 121 patients (76%) died of anorectal melanoma. Patients presenting with regional (34%) or distant metastases (24%) had significantly shorter disease-specific survival compared to those with disease localized to the anorectum (42%). Of the 71 anorectal melanoma tumors analyzed for hotspot genetic alterations, somatic mutations involving the KIT gene (24%) were most common followed by NRAS (19%). Increasing primary tumor thickness, lymphovascular invasion, and absence of regression also correlated with shorter disease-specific survival. Primary tumor parameters correlated with shorter disease-specific survival in patients presenting with localized disease (tumor thickness) or regional metastases (tumor thickness, absence of regression, and lymphovascular invasion), but not in patients presenting with distant metastases. Grouping of patients according to a schema based on modifications of the 8th edition AJCC cutaneous melanoma staging system stratified survival in anorectal melanoma. Our findings support stage-specific associations between primary tumor parameters and disease-specific survival in anorectal melanoma. Moreover, the AJCC cutaneous melanoma staging system and minor modifications of it predicted survival among anorectal melanoma patients

A first assessment of the genetic diversity of Mycobacterium tuberculosis complex in Cambodia

<p>Abstract</p> <p>Background</p> <p>Cambodia is among the 22 high-burden TB countries, and has one of the highest rates of TB in South-East Asia. This study aimed to describe the genetic diversity among clinical <it>Mycobacterium tuberculosis </it>complex (MTC) isolates collected in Cambodia and to relate these findings to genetic diversity data from neighboring countries.</p> <p>Methods</p> <p>We characterized by 24 VNTR loci genotyping and spoligotyping 105 <it>Mycobacterium tuberculosis </it>clinical isolates collected between 2007 and 2008 in the region of Phnom-Penh, Cambodia, enriched in multidrug-resistant (MDR) isolates (n = 33).</p> <p>Results</p> <p>Classical spoligotyping confirmed that the East-African Indian (EAI) lineage is highly prevalent in this area (60%-68% respectively in whole sample and among non-MDR isolates). Beijing lineage is also largely represented (30% in whole sample, 21% among non-MDR isolates, OR = 4.51, CI_95%[1.77, 11.51]) whereas CAS lineage was absent. The 24 loci MIRU-VNTR typing scheme distinguished 90 patterns with only 13 multi-isolates clusters covering 28 isolates. The clustering of EAI strains could be achieved with only 8 VNTR combined with spoligotyping, which could serve as a performing, easy and cheap genotyping standard for this family. Extended spoligotyping suggested relatedness of some unclassified "T1 ancestors" or "Manu" isolates with modern strains and provided finer resolution.</p> <p>Conclusions</p> <p>The genetic diversity of MTC in Cambodia is driven by the EAI and the Beijing families. We validate the usefulness of the extended spoligotyping format in combination with 8 VNTR for EAI isolates in this region.</p

Breast cancer management pathways during the COVID-19 pandemic: outcomes from the UK ‘Alert Level 4’ phase of the B-MaP-C study

Abstract: Background: The B-MaP-C study aimed to determine alterations to breast cancer (BC) management during the peak transmission period of the UK COVID-19 pandemic and the potential impact of these treatment decisions. Methods: This was a national cohort study of patients with early BC undergoing multidisciplinary team (MDT)-guided treatment recommendations during the pandemic, designated ‘standard’ or ‘COVID-altered’, in the preoperative, operative and post-operative setting. Findings: Of 3776 patients (from 64 UK units) in the study, 2246 (59%) had ‘COVID-altered’ management. ‘Bridging’ endocrine therapy was used (n = 951) where theatre capacity was reduced. There was increasing access to COVID-19 low-risk theatres during the study period (59%). In line with national guidance, immediate breast reconstruction was avoided (n = 299). Where adjuvant chemotherapy was omitted (n = 81), the median benefit was only 3% (IQR 2–9%) using ‘NHS Predict’. There was the rapid adoption of new evidence-based hypofractionated radiotherapy (n = 781, from 46 units). Only 14 patients (1%) tested positive for SARS-CoV-2 during their treatment journey. Conclusions: The majority of ‘COVID-altered’ management decisions were largely in line with pre-COVID evidence-based guidelines, implying that breast cancer survival outcomes are unlikely to be negatively impacted by the pandemic. However, in this study, the potential impact of delays to BC presentation or diagnosis remains unknown

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Anticancer Activity of Smallanthus sonchifolius Methanol Extract against Human Hepatocellular Carcinoma Cells

Background: This research aimed to investigate the cytotoxicity of methanol extract of Smallanthus sonchifolius leaf (YLE) against a human hepatocellular carcinoma cell line (HepG2). This plant is currently used as a traditional herbal remedy in the treatment of liver diseases in some rural parts of Myanmar. Methods: The cytotoxic activity of the plant extract against the cancerous cell line was assessed using an MTT assay. YLE demonstrated a significant effect (IC50 = 58.2 &plusmn; 1.9 &mu;g/mL) on anti-cancer activity, which was further investigated using various assays including an in vitro cell migration assay, a colony formation assay, cell cycle analysis, western blot analysis, and a ROS assay. The significance of the phytochemical constituents of YLE could be identified using LC/Q-TOF-MS techniques. Results: We putatively identified the active components in YLE, which were possibly melampolide-type sesquiterpenoids. YLE showed an inhibitory effect on HepG2 cell proliferation and cell migration. YLE also induced cell cycle arrest and necrosis in a dose-dependent manner. Additionally, YLE significantly suppressed ROS formation in HepG2 cells. Conclusions: These findings suggest that YLE is sufficient for application as a promising anti-liver drug in herbal medicine