2020 Vol. 34, No. 4
Type 2 diabetes (T2D) and cardiovascular disease (CVD) share many risk factors such as obesity, unhealthy lifestyle, and metabolic syndrome, whose accumulation over years leads to disease onset. However, while lowering plasma low-density lipoprotein cholesterol (LDLC) is cardio-protective, novel evidence have recognised a role for common LDLC-lowering variants (e.g. in HMGCR, PCSK9, and LDLR) and widely used hypocholesterolemic drugs that mimic the effects of some of these variants (statins) in higher risk for T2D. As these conditions decrease plasma LDLC by increasing tissue-uptake of LDL, a role for LDL receptor (LDLR) pathway was proposed. While underlying mechanisms remain to be fully elucidated, work from our lab reported that native LDL directly provoke the dysfunction of human white adipose tissue (WAT) and the activation of WAT NLRP3 (Nucleotide-binding domain and Leucine-rich repeat Receptor, containing a Pyrin domain 3) inflammasome, which play a major role in the etiology of T2D. However, while elevated plasma numbers of apolipoprotein B (apoB)-containing lipoproteins (measured as apoB, mostly as LDL) is associated with WAT dysfunction and related risk factors for T2D in our cohort, this relation was strengthened in regression analysis by lower plasma proprotein convertase subtilisin/kexin type 9 (PCSK9). This supports a central role for upregulated pathway of LDLR and/or other receptors regulated by PCSK9 such as cluster of differentiation 36 (CD36) in LDL-induced anomalies. Targeting receptor-mediated uptake of LDL into WAT may reduce WAT inflammation, WAT dysfunction, and related risk for T2D without increasing the risk for CVD.
Glutamine and glutamate are major bioenergy substrates for normal and cancer cell growth. Cancer cells need more biofuel than normal tissues for energy supply, anti-oxidation activity and biomass production. Genes related to metabolic chains in many cancers are somehow mutated, which makes cancer cells more glutamate dependent. Meanwhile, glutamate is an excitatory neurotransmitter for conducting signals through binding with different types of receptors in central neuron system. Interestingly, increasing evidences have shown involvement of glutamate signaling, guided through their receptors, in human malignancy. Dysregulation of glutamate transporters, such as excitatory amino acid transporter and cystine/glutamate antiporter system, also generates excessive extracellular glutamate, which in turn, activates glutamate receptors on cancer cells and results in malignant growth. These features make glutamate an attractive target for anti-cancer drug development with some glutamate targeted but blood brain barrier impermeable anti-psychosis drugs under consideration. We discussed the relevant progressions and drawbacks in this field herein.
Postoperative sleep disturbance is a common occurrence with significant adverse effects on patients including delayed recovery, impairment of cognitive function, pain sensitivity and cardiovascular events. The development of postoperative sleep disturbance is multifactorial and involves the surgical inflammatory response, the severity of surgical trauma, pain, anxiety, the use of anesthetics and environmental factors such as nocturnal noise and light levels. Many of these factors can be managed perioperatively to minimize the deleterious impact on sleep. Pharmacological and non-pharmacological treatment strategies for postoperative sleep disturbance include dexmedetomidine, zolpidem, melatonin, enhanced recovery after surgery (ERAS) protocol and controlling of environmental noise and light levels. It is likely that a combination of pharmacological and non-pharmacological therapies will have the greatest impact; however, further research is required before their use can be routinely recommended.
One of the difficulties in creating a blood substitute on the basis of human haemoglobin (Hb) is the toxic nature of Hb when it is outside the safe environment of the red blood cells. The plasma protein haptoglobin (Hp) takes care of the Hb physiologically leaked into the plasma – it binds Hb and makes it much less toxic while retaining the Hb's high oxygen transporting capacity. We used Electron Paramagnetic Resonance (EPR) spectroscopy to show that the protein bound radical induced by H2O2 in Hb and Hp-Hb complex is formed on the same tyrosine residue(s), but, in the complex, the radical is found in a more hydrophobic environment and decays slower than in unbound Hb, thus mitigating its oxidative capacity. The data obtained in this study might set new directions in engineering blood substitutes for transfusion that would have the oxygen transporting efficiency typical of Hb, but which would be non-toxic.
Immune cell accumulation and white matter anomaly are common features of HIV (human immunodeficiency virus) -infected patients in combination antiretroviral therapy (cART) era. Neuroimaging tests on cART treated patients displayed prominent diffuse white matter lesions. Notably, immune cell nodular lesion (NL) was a conspicuous type of pathological change in HIV/SIV (simian immunodeficiency virus) infected brain before cART. Therefore, we used SIV infected brain to investigate the distribution of those NLs in gray and white matters. We found a significant higher number of NLs in white matter than that in gray matter. However, virus infection correlated with macrophage NLs but not with microglia NLs, especially in white matter. In addition, NLs interrupted white matter integrity more severely, since even tiny nodules could disconnect nerve fibers in white matter tracts. In the gray matter with dense myelinated axons, NLs obviously encroached those fibers; in the area of few myelinated axons, small nodules well co-localized with extracellular matrix between neurons.
In this report, we aimed to analyze the prevalence of undernutrition and associated factors among children under 5 years of age in Lhaviyani Atoll, Maldives. A total of 800 children (under 5 years old) and their mothers were selected for this study. Data was collected by using a pretested questionnaire and anthropometric measurements were taken from the hospital record book. Chi-square tests and multivariate logistic regression were used to find the association between nutritional status and determinants. The distribution of height for age and weight for age in surveyed children in Maldives was skewed to the left compared with the WHO standard. The prevalence of undernutrition based on underweight (10.75%), stunting (13.5%), and wasting (9.60%) was estimated to be 23.85% among children. Child age, gender and mother's education were significantly associated with undernutrition (P<0.05). Our survey highlighted that better nutritional interventions are needed to improve child health in this region.
Currently, 18F-FDG coincidence SPECT (Co-SPECT)/CT scan still serves as an important tool for diagnosis, staging, and evaluation of cancer treatment in developing countries. We implemented full physical corrections (FPC) to Co-SPECT (quantitative Co-SPECT) to improve the image resolution and contrast along with the capability for image quantitation. FPC included attenuation, scatter, resolution recovery, and noise reduction. A standard NEMA phantom filled with 10:1 F-18 activity concentration ratio in spheres and background was utilized to evaluate image performance. Subsequently, 15 patients with histologically confirmed thoracic carcinomas were included to undergo a 18F-FDG Co-SPECT/CT scan followed by a 18F-FDG PET/CT scan. Functional parameters as SUVmax, SUVmean, SULpeak, and MTV from both quantitative Co-SPECT and PET were analyzed. Image resolution of Co-SPECT for NEMA phantom was improved to reveal the smallest sphere from a diameter of 28 mm to 22 mm (17 mm for PET). The image contrast was enhanced from 1.7 to 6.32 (6.69 for PET) with slightly degraded uniformity in background (3.1% vs. 6.7%) (5.6% for PET). Patients' SUVmax, SUVmean, SULpeak, and MTV measured from quantitative Co-SPECT were overall highly correlated with those from PET (r=0.82–0.88). Adjustment of the threshold of SUVmax and SUV to determine SUVmean and MTV did not further change the correlations with PET (r=0.81–0.88). Adding full physical corrections to Co-SPECT images can significantly improve image resolution and contrast to reveal smaller tumor lesions along with the capability to quantify functional parameters like PET/CT.
Intraventricular metastases are a rare occurrence, particularly from a primary colorectal malignancy. To our knowledge, this is the first report of intraventricular metastasis from rectal cancer. A 72-year-old male presented with a new diagnosis of multiple intraventricular lesions, an anterior mediastinal mass and a rectal mass. His workup revealed rectal adenocarcinoma with intraventricular metastases and an incidental thymoma. Ommaya reservoir placement was performed via an awake procedure rather than under general anesthesia due to airway concerns. Cerebrospinal fluid (CSF) cytology was positive for malignancy and consistent with adenocarcinoma. Two weeks postoperatively, the patient underwent whole brain radiation. Although rare, this diagnosis should always be considered in the differential for solitary or multiple intraventricular lesions. CSF sampling is a useful alternative to intraventricular biopsy for diagnosis of intraventricular metastases. Awake placement of Ommaya reservoir is a safe option in the management of patients with intraventricular metastases, especially those who cannot undergo general anesthesia.