Sleep Quality of Patients with Differentiated Thyroid Cancer

Objective

We aimed to measure prevalence of sleep disturbance in patients with differentiated thyroid cancer (DTC) by calculating Pittsburgh Sleep Quality Index (PSQI), and compare these data with patients with benign thyroid nodules or normal participants.

Methods

Three groups of patients participated in this cross-sectional study. In the first group, 162 patients with DTC received total thyroidectomy, and then ¹³¹I therapy. The second group consisted of 84 patients with benign thyroid nodules, who received partial thyroidectomy. The third group was 78 normal healthy control cases. PSQI was used to assess the sleep quality. Inter-group differences were analyzed by Kruskal-Wallis test or independent samples T test. χ² test was also used to check prevalence differences of poor sleep quality among the groups. Differences of PSQI score and poor sleep quality prevalence before and after ¹³¹I therapy in the same group of DTC participants were analyzed by paired T test and Mcnemar''s test.

Results

Higher PSQI score (7.59 ± 4.21) and higher rate of poor sleep quality (54.32%) were shown in DTC patients than in any other group. After ¹³¹I therapy, PSQI score and prevalence of poor sleep quality in DTC patients increased significantly to 8.78 ± 4.72 and 70.99%. Then DTC patients were divided into two subgroups based on their metastatic status. DTC patients with metastasis (87/162 cases, 53.70%) had significantly higher PSQI score (10.87 ± 5.18) and higher prevalence of poor sleep quality (79.31%).

Conclusion

DTC patients suffer from sleep disturbance, ¹³¹I therapy and awareness of metastatic status could worsen sleep problem. Psychological fear of cancer, nuclear medicine therapy and metastasis could be one major underlying reason. Longitude and interventional studies are necessary for further investigations.     

Dysregulated Hepatic Methionine Metabolism Drives Homocysteine Elevation in Diet-Induced Nonalcoholic Fatty Liver Disease

Methionine metabolism plays a central role in methylation reactions, production of glutathione and methylarginines, and modulating homocysteine levels. The mechanisms by which these are affected in NAFLD are not fully understood. The aim is to perform a metabolomic, molecular and epigenetic analyses of hepatic methionine metabolism in diet-induced NAFLD. Female 129S1/SvlmJ;C57Bl/6J mice were fed a chow (n = 6) or high-fat high-cholesterol (HFHC) diet (n = 8) for 52 weeks. Metabolomic study, enzymatic expression and DNA methylation analyses were performed. HFHC diet led to weight gain, marked steatosis and extensive fibrosis. In the methionine cycle, hepatic methionine was depleted (30%, p< 0.01) while s-adenosylmethionine (SAM)/methionine ratio (p< 0.05), s-adenosylhomocysteine (SAH) (35%, p< 0.01) and homocysteine (25%, p< 0.01) were increased significantly. SAH hydrolase protein levels decreased significantly (p <0.01). Serine, a substrate for both homocysteine remethylation and transsulfuration, was depleted (45%, p< 0.01). In the transsulfuration pathway, cystathionine and cysteine trended upward while glutathione decreased significantly (p< 0.05). In the transmethylation pathway, levels of glycine N-methyltransferase (GNMT), the most abundant methyltransferase in the liver, decreased. The phosphatidylcholine (PC)/ phosphatidylethanolamine (PE) ratio increased significantly (p< 0.01), indicative of increased phosphatidylethanolamine methyltransferase (PEMT) activity. The protein levels of protein arginine methytransferase 1 (PRMT1) increased significantly, but its products, monomethylarginine (MMA) and asymmetric dimethylarginine (ADMA), decreased significantly. Circulating ADMA increased and approached significance (p< 0.06). Protein expression of methionine adenosyltransferase 1A, cystathionine β-synthase, γ-glutamylcysteine synthetase, betaine-homocysteine methyltransferase, and methionine synthase remained unchanged. Although gene expression of the DNA methyltransferase Dnmt3a decreased, the global DNA methylation was unaltered. Among individual genes, only HMG-CoA reductase (Hmgcr) was hypermethylated, and no methylation changes were observed in fatty acid synthase (Fasn), nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (Nfκb1), c-Jun, B-cell lymphoma 2 (Bcl-2) and Caspase 3. NAFLD was associated with hepatic methionine deficiency and homocysteine elevation, resulting mainly from impaired homocysteine remethylation, and aberrancy in methyltransferase reactions. Despite increased PRMT1 expression, hepatic ADMA was depleted while circulating ADMA was increased, suggesting increased export to circulation.     

Behavioral and electrophysiological analysis of general anesthesia in 3 background strains of Drosophila melanogaster

General anesthetics achieve behavioral unresponsiveness via a mechanism that is incompletely understood. The study of genetic model systems such as the fruit fly Drosophila melanogaster is crucial to advancing our understanding of how anesthetic drugs render animals unresponsive. Previous studies have shown that wild-type control strains differ significantly in their sensitivity to general anesthetics, which potentially introduces confounding factors for comparing genetic mutations placed on these wild-type backgrounds. Here, we examined a variety of behavioral and electrophysiological endpoints in Drosophila, in both adult and larval animals. We characterized these endpoints in 3 commonly used fly strains: wild-type Canton Special (CS), and 2 commonly used white-eyed strains, isoCJ1 and w¹¹¹⁸. We found that CS and isoCJ1 show remarkably similar sensitivity to isoflurane across a variety of behavioral and electrophysiological endpoints. In contrast, w¹¹¹⁸ is resistant to isoflurane compared to the other 2 strains at both the adult and larval stages. This resistance is however not reflected at the level of neurotransmitter release at the larval neuromuscular junction (NMJ). This suggests that the w¹¹¹⁸ strain harbors another mutation that produces isoflurane resistance, by acting on an arousal pathway that is most likely preserved between larval and adult brains. This mutation probably also affects sleep, as marked differences between isoCJ1 and w¹¹¹⁸ have also recently been found for behavioral responsiveness and sleep intensity measures.     

Systemic and Cardiac Depletion of M2 Macrophage through CSF-1R Signaling Inhibition Alters Cardiac Function Post Myocardial Infarction

The heart hosts tissue resident macrophages which are capable of modulating cardiac inflammation and function by multiple mechanisms. At present, the consequences of phenotypic diversity in macrophages in the heart are incompletely understood. The contribution of cardiac M2-polarized macrophages to the resolution of inflammation and repair response following myocardial infarction remains to be fully defined. In this study, the role of M2 macrophages was investigated utilising a specific CSF-1 receptor signalling inhibition strategy to achieve their depletion. In mice, oral administration of GW2580, a CSF-1R kinase inhibitor, induced significant decreases in Gr1^lo and F4/80^hi monocyte populations in the circulation and the spleen. GW2580 administration also induced a significant depletion of M2 macrophages in the heart after 1 week treatment as well as a reduction of cardiac arginase1 and CD206 gene expression indicative of M2 macrophage activity. In a murine myocardial infarction model, reduced M2 macrophage content was associated with increased M1-related gene expression (IL-6 and IL-1β), and decreased M2-related gene expression (Arginase1 and CD206) in the heart of GW2580-treated animals versus vehicle-treated controls. M2 depletion was also associated with a loss in left ventricular contractile function, infarct enlargement, decreased collagen staining and increased inflammatory cell infiltration into the infarct zone, specifically neutrophils and M1 macrophages. Taken together, these data indicate that CSF-1R signalling is critical for maintaining cardiac tissue resident M2-polarized macrophage population, which is required for the resolution of inflammation post myocardial infarction and, in turn, for preservation of ventricular function.     

Lumenal Protein within Secretory Granules Affects Fusion Pore Expansion

It is often assumed that upon fusion of the secretory granule membrane with the plasma membrane, lumenal contents are rapidly discharged and dispersed into the extracellular medium. Although this is the case for low-molecular-weight neurotransmitters and some proteins, there are numerous examples of the dispersal of a protein being delayed for many seconds after fusion. We have investigated the role of fusion-pore expansion in determining the contrasting discharge rates of fluorescent-tagged neuropeptide-Y (NPY) (within 200 ms) and tissue plasminogen activator (tPA) (over many seconds) in adrenal chromaffin cells. The endogenous proteins are expressed in separate chromaffin cell subpopulations. Fusion pore expansion was measured by two independent methods, orientation of a fluorescent probe within the plasma membrane using polarized total internal reflection fluorescence microscopy and amperometry of released catecholamine. Together, they probe the continuum of the fusion-pore duration, from milliseconds to many seconds after fusion. Polarized total internal reflection fluorescence microscopy revealed that 71% of the fusion events of tPA-cer-containing granules maintained curvature for >10 s, with approximately half of the structures likely connected to the plasma membrane by a short narrow neck. Such events were not commonly observed upon fusion of NPY-cer-containing granules. Amperometry revealed that the expression of tPA-green fluorescent protein (GFP) prolonged the duration of the prespike foot ∼2.5-fold compared to NPY-GFP-expressing cells and nontransfected cells, indicating that expansion of the initial fusion pore in tPA granules was delayed. The t_1/2 of the main catecholamine spike was also increased, consistent with a prolonged delay of fusion-pore expansion. tPA added extracellularly bound to the lumenal surface of fused granules. We propose that tPA within the granule lumen controls its own discharge. Its intrinsic biochemistry determines not only its extracellular action but also the characteristics of its presentation to the extracellular milieu.     

Prokaryotic and eukaryotic integral membrane proteins have similar architecture

Integral membrane proteins constitute a major constituent of lipid bilayer both in prokaryotes and eukaryotes. The statistical analysis was carried out to determine the bias in amino acid distribution between prokaryotic and eukaryotic integral membrane proteins (pIntMPs and eIntMPs). Our results indicate that both pIntMPs and eIntMPs demonstrate the striking similarity in amino acid distribution in their transmembrane and extramembranous region. pIntMPs have relatively greater functional importance for Gly and Asn in comparison to eIntMPs.     

Basidiobolomycosis of the Nose and Face: A Case Report and a Mini-Review of Unusual Cases of Basidiobolomycosis

Background  

Subcutaneous zygomycosis is a chronic infection caused by fungus of the order Entomophthorales. It can have varying presentations and presents in the nose and face area with gradually progressing subcutaneous swelling that may be difficult to diagnose unless a strong suspicion of fungal involvement is maintained. We present a case of subcutaneous zygomycosis in a 35-year-old male patient, resident of a North Indian state. The patient was diagnosed to be suffering from subcutaneous zygomycosis, the causative agent being Basidiobolus ranarum identified on culture and lactophenol cotton blue mount preparation. He responded well to treatment with Itraconazole and Terbinafine and is asymptomatic on follow-up.     

Trio under threat: can we secure the future of rhinos,elephants and tigers in Malaysia?

Three of Malaysia’s endangered large mammal species are experiencing contrasting futures. Populations of the Sumatran rhino (Dicerorhinus sumatrensis) have dwindled to critically low numbers in Peninsular Malaysia (current estimates need to be revised) and the state of Sabah (less than 40 individuals estimated). In the latter region, a bold intervention involving the translocation of isolated rhinos is being developed to concentrate them into a protected area to improve reproduction success rates. For the Asian elephant (Elephas maximus), recently established baselines for Peninsular Malaysia (0.09 elephants/km² estimated from one site) and Sabah (between 0.56 and 2.15 elephants/km² estimated from four sites) seem to indicate globally significant populations based on dung count surveys. Similar surveys are required to monitor elephant population trends at these sites and to determine baselines elsewhere. The population status of the Malayan tiger (Panthera tigris jacksoni) in Peninsular Malaysia, however, remains uncertain as only a couple of scientifically defensible camera-trapping surveys (1.66 and 2.59 tigers/100 km² estimated from two sites) have been conducted to date. As conservation resources are limited, it may be prudent to focus tiger monitoring and protection efforts in priority areas identified by the National Tiger Action Plan for Malaysia. Apart from reviewing the conservation status of rhinos, elephants and tigers and threats facing them, we highlight existing and novel conservation initiatives, policies and frameworks that can help secure the long-term future of these iconic species in Malaysia.