mFOLFIRINOX versus mFOLFOX 6 as adjuvant treatment for high-risk stage III colon cancer - the FROST trial: study protocol for a multicenter, randomized controlled, phase II trial.

BACKGROUND: High-risk stage III colon cancer has a considerably poorer prognosis than stage II and low-risk stage III colon cancers. Nevertheless, most guidelines recommend similar adjuvant treatment approaches for all these stages despite the dearth of research focusing on high-risk stage III colon cancer and the potential for improved prognosis with intensive adjuvant treatment. Given the the proven efficacy of triplet chemotherapy in metastatic colorectal cancer treatment, the goal of this study is to evaluate the oncologic efficacy and safety of mFOLFIRINOX in comparison to those of the current standard of care, mFOLFOX 6, as an adjuvant treatment for patients diagnosed with high-risk stage III colon cancer after radical resection. METHODS: This multicenter, randomized (1:1), open-label, phase II trial will assess and compare the effectiveness and toxicity of mFOLFIRINOX and mFOLFOX 6 in patients with high-risk stage III colon cancer after radical resection. The goal of the trial is to enroll 312 eligible patients, from 11 institutes, aged between 20 and 70 years, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, or between 70 and 75 with an ECOG performance status of 0. Patients will be randomized into two arms - Arm A, the experimental arm, and Arm B, the reference arm - and will receive 12 cycles of mFOLFIRINOX and mFOLFOX 6 every 2 weeks, respectively. The primary endpoint of this study is the 3-year disease-free survival, and secondary endpoints include the 3-year overall survival and treatment toxicity. DISCUSSION: The Frost trial would help determine the oncologic efficacy and safety of adjuvant triplet chemotherapy for high-risk stage III colon cancers and ultimately improve prognoses. TRIAL REGISTRATION: ClinicalTrials.gov NCT05179889, registered on 17 December 2021.

Dietary Supplementation of Bacillus sp. PM8313 with ß-glucan Modulates the Intestinal Microbiota of Red Sea Bream (Pagrus major) to Increase Growth, Immunity, and Disease Resistance.

A 56-day feeding trial was conducted to determine the effect of dietary supplementation with Bacillus sp. isolated from the intestines of red sea bream on the growth performance, immunity, and gut microbiome composition of red sea bream. Three diets (a control diet and two treatments) were formulated without Bacillus sp. PM8313 or ß-glucan (control, CD), 1 × 108 CFU g-1 PM8313 (BSD), and 1 × 108 CFU g-1 PM8313 + 0.1% ß-glucan (BGSD). At the end of the experiment, the weight, specific growth rate, feed conversion ratio, and protein efficiency ratio of the fish in the BSD and BGSD diet groups were significantly improved than those of the control group (P < 0.05). Additionally, amylase and trypsin activities were significantly higher (P < 0.05) in both groups compared to the control. Superoxide dismutase and lysozyme activity, which are serum non-specific immune responses, only increased in the BGSD group. The two treatment groups exhibited a marked difference in the intestinal microbiota composition compared to the control group. Furthermore, the treatment groups exhibited an upregulation of IL-6 and NF-κb, coupled with high survival rates when challenged with Edwardsiella tarda. Therefore, dietary supplementation with PM8313 improved the growth performance, digestive enzyme activity, non-specific immunity, and pathogen resistance of red sea bream, in addition to affecting the composition of its intestinal microflora.

Characterization of a Bacillus sp. KRF-7 isolated from the intestine of rockfish and effects of dietary supplementation with mannan oligosaccharide in rockfish aquaculture.

The purpose of this study was to characterize the bacteria isolated from rockfish intestines and to investigate the effects of feed supplementation in rockfish aquaculture. Bacillus sp. KRF-7 isolated from the intestine of rockfish (Sebastes schlegelii) was demonstrated to be safe based on in vitro tests confirming the absence of hemolysis, cytotoxicity, and genes with toxigenic potential. In a feeding trial, providing a supplemental diet of 1 × 108 CFU g-1Bacillus sp. KRF-7 was observed to positively alter the weight gain, specific growth rate, feed conversion ratio, and protein efficiency ratio of juvenile rockfish. KRF-7 supplementation showed positive regulation of nonspecific immune parameters, such as superoxide dismutase, lysozyme activity, and myeloperoxidase activity. This analysis also revealed a change in the composition of the intestinal microbiota at the phylum level from Proteobacteria to Firmicutes. In both the kidney and spleen, the expression levels of IL-10, NF-κB, and B cell activating factors in the KRF-7-supplemented group were significantly increased compared to those in the control group. Therefore, this study verified the safety of KRF-7 isolated from the intestine of rockfish and suggests that dietary supplementation with KRF-7 enhances the growth performance of rockfish and has beneficial effects on the regulation of the intestinal microbiota and immune response.

A microfluidic gradient device for drug screening with human iPSC-derived motoneurons.

We developed a microfluidic gradient device to utilize as a drug screening system with human induced pluripotent stem cell (hiPSC)-derived motoneurons. The microfluidic channel was asymmetrically designed to generate the concentration gradients and a micropillar array was used to trap and culture the motoneuron spheroids containing motoneurons for 9 days. We optimized the concentration gradients in the microfluidic device using a computational fluid dynamics (CFD) model. We also observed that the motoneuron spheroid-derived neurite network was generated in response to the concentration gradients of riluzole in the microfluidic device. Therefore, this microfluidic gradient device could be useful for screening of various drugs for neurological disease applications.

The Effect of Vitamin D Supplementation in Patients with Acute Traumatic Brain Injury.

OBJECTIVE: To investigate the acute and long-term effects of vitamin D supplementation on the recovery of patients with traumatic brain injury (TBI). METHODS: A retrospective study was conducted involving 345 patients with TBI who visited a single trauma center. Vitamin D serum levels were measured without supplementation at admission, 1 month, and 3 months post-TBI (control group) from August to December 2016. From January 2017, vitamin D supplementation was provided to patients with TBI with low vitamin D serum levels at admission (supplement group). The outcomes were investigated by assessing performance function (Extended Glasgow Outcome Scale) and cognitive function (Mini-Mental Status Examination, and Clinical Dementia Rating) at 1 week and 3 months post-TBI. RESULTS: The mean vitamin D serum level in patients with TBI at admission was 13.62 ± 9.01 ng/mL. The level significantly increased from 14.03 ± 8.68 ng/mL at admission to 37.42 ± 12.57 ng/mL at 3 months post TBI in the supplement group (P < 0.001). The cognitive outcomes (Mini-Mental Status Examination/Clinical Dementia Rating, P = 0.042/P = 0.044) and GOS-E score (total TBI, P = 0.003; mild-to-moderate TBI, P = 0.002) significantly improved from the first week to 3 months post TBI in the patients with vitamin D supplementation. CONCLUSIONS: Administration of vitamin D supplements in mild-to-moderate TBI patients with significant vitamin D deficiency during the acute phase of the injury may improve long-term performance and cognitive outcomes. Therefore, the treatment strategies should be individually planned for the patients with TBI based on their baseline vitamin D level.

Generation of uniform-sized multicellular tumor spheroids using hydrogel microwells for advanced drug screening.

Even though in vitro co-culture tumor spheroid model plays an important role in screening drug candidates, its wide applications are currently limited due to the lack of reliable and high throughput methods for generating well-defined and 3D complex co-culture structures. Herein, we report the development of a hydrogel microwell array to generate uniform-sized multicellular tumor spheroids. Our developed multicellular tumor spheroids are structurally well-defined, robust and can be easily transferred into the widely used 2D culture substrates while maintaining our designed multicellular 3D-sphere structures. Moreover, to develop effective anti-cancer therapeutics we integrated our recently developed gold-graphene hybrid nanomaterial (Au@GO)-based photothermal cancer therapy into a series of multicellular tumor spheroid co-culture system. The multicellular tumor spheroids were harvested onto a two-dimensional (2D) substrate, under preservation of their three-dimensional (3D) structure, to evaluate the photothermal therapy effectiveness of graphene oxide (GO)-wrapped gold nanoparticles (Au@GO). From the model of co-culture spheroids of HeLa/Ovarian cancer and HeLa/human umbilical vein endothelial cell (HUVEC), we observed that Au@GO nanoparticles displayed selectivity towards the fast-dividing HeLa cells, which could not be observed to this extent in 2D cultures. Overall, our developed uniform-sized 3D multicellular tumor spheroid could be a powerful tool for anticancer drug screening applications.

Botulinum Toxin Injections and Electrical Stimulation for Spastic Paresis Improve Active Hand Function Following Stroke.

Botulinum toxin type A (BTX-A) injections improve muscle tone and range of motion (ROM) among stroke patients with upper limb spasticity. However, the efficacy of BTX-A injections for improving active function is unclear. We aimed to determine whether BTX-A injections with electrical stimulation (ES) of hand muscles could improve active hand function (AHF) among chronic stroke patients. Our open-label, pilot study included 15 chronic stroke patients. Two weeks after BTX-A injections into the finger and/or wrist flexors, ES of finger extensors was performed while wearing a wrist brace for 4 weeks (5 days per week; 30-min sessions). Various outcomes were assessed at baseline, immediately before BTX-A injections, and 2 and 6 weeks after BTX-A injections. After the intervention, we noted significant improvements in Box and Block test results, Action Research Arm Test results, the number of repeated finger flexions/extensions, which reflect AHF, and flexor spasticity. Moreover, significant improvements in active ROM of wrist extension values were accompanied by marginally significant changes in Medical Research Council wrist extensor and active ROM of wrist flexion values. In conclusion, BTX-A injections into the finger and/or wrist flexors followed by ES of finger extensors improve AHF among chronic stroke patients.

Physicochemical properties, production, and biological functionality of poly-γ-d-glutamic acid with constant molecular weight from halotolerant Bacillus sp. SJ-10.

Poly-γ-glutamic acid (γ-PGA) is an unusual anionic homopolyamide that is biodegradable, edible, and nontoxic. It has a wide variety of industrial applications depending on its combined cations, and molecular weight. In this study, extracellular viscous γ-PGA produced by halotolerant Bacillus sp. SJ-10 isolated from a traditional Korean salted-fermented seafood was purified and characterized. The physicochemical analysis indicated that the γ-PGA produced by Bacillus sp. SJ-10 consists primarily of d-glutamic acid residues combined with sodium cations. When batch fermentation was performed with 8% NaCl for 3 d, Bacillus sp. SJ-10 produced approximately 24.7g/L γ-PGA with a molecular weight of approximately 400 kilodaltons (kDa). Under fermentation conditions with 6% NaCl, the maximum yield was 26.2g/L regardless of the molecular weight. The γ-PGA sodium salt with a molecular weight of 400kDa exhibited antioxidant activity by scavenging 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) radicals and reducing molybdenum, with maximal scavenging activity at 0.5mg/mL and reducing activity at 1mg/mL (20µg ascorbic acid-equivalent), respectively. These results suggest the potential use of γ-PGA in the food, cosmetic, and biomedical industries for its antioxidant qualities. Our results also provide an economical method for controlling the molecular weight of the γ-PGA produced.

Inhibition of collagenase and melanogenesis by ethanol extracts of Orostachys japonicus A. Berger: possible involvement of Erk and Akt signaling pathways in melanoma cells.

Orostachys japonicus is an herb that contains several functional components and has traditionally been used to treat various diseases in Asia. In this study, bioactive components from different parts of the O. japonicus plant were investigated, and the contents of the functional components in ethanol extracts of O. japonicus cultivated in Korea and China were compared. The antioxidant effects of O. japonicus ethanol extracts were investigated using Raw 264.7 cells. It was found that 2,2-diphenyl-1-picrylhydrazyl radical-scavenging activity was significantly decreased in the cells treated with the extracts. Moreover, the novel inhibitory functions of O. japonicus extracts on collagenase, elastase, and tyrosinase were established. We also found that O. japonicus extracts strongly inhibited melanin synthesis in B16F10 melanoma cells by decreasing MITF protein levels and activating the Erk and Akt signaling pathways. Thus, these findings would be useful for developing new cosmetic and pharmaceutical formulations based on O. japonicus extracts.

Hydrogel microfluidic co-culture device for photothermal therapy and cancer migration.

We developed the photo-crosslinkable hydrogel microfluidic co-culture device to study photothermal therapy and cancer cell migration. To culture MCF7 human breast carcinoma cells and metastatic U87MG human glioblastoma in the microfluidic device, we used 10 w/v% gelatin methacrylate (GelMA) hydrogels as a semi-permeable physical barrier. We demonstrated the effect of gold nanorod on photothermal therapy of cancer cells in the microfluidic co-culture device. Interestingly, we observed that metastatic U87MG human glioblastoma largely migrated toward vascular endothelial growth factor (VEGF)-treated GelMA hydrogel-embedding microchannels. The main advantage of this hydrogel microfluidic co-culture device is to simultaneously analyze the physiological migration behaviors of two cancer cells with different physiochemical motilities and study gold nanorod-mediated photothermal therapy effect. Therefore, this hydrogel microfluidic co-culture device could be a potentially powerful tool for photothermal therapy and cancer cell migration applications.

Comparison of the effects of dietary single and multi-probiotics on growth, non-specific immune responses and disease resistance in starry flounder, Platichthys stellatus.

An 8-week feeding trial was conducted to evaluate the effects of dietary probiotics on growth performance and non-specific immune responses in starry flounder, Platichthys stellatus. Fish averaging 46.5 ± 0.65 g (mean ± SD) were fed one of the six experimental diets; one control (Cont), and five other diets were prepared by supplementing single-probiotics 1 (Bacillus subtilis; SP1, 2 × 109 CFU kg-1 diet), single-probiotics 2 (Bacillus licheniformis; SP2, 2 × 109 CFU kg-1 diet), multi-probiotics 1 (Bacillus subtilis + Bacillus licheniformis; MP1, 2 × 109 CFU kg-1 diet), multi-probiotics 2 (commercial probiotics; Bacillus subtills + Bacillus licheniformis + Paenibacillus polymyxa + Aspergillus oryzae + Saccharomyces cerevisiae; MP2, 2 × 109 CFU kg-1 diet) and oxytetracycline (OTC) at 5 g OTC kg-1 diet. At the end of 8 weeks feeding trial, weight gain (WG) and specific growth rate (SGR) of fish fed SP1, MP1 and MP2 diets were significantly higher than those of fish fed control diet (P < 0.05). Superoxide dismutase (SOD) activity of fish fed MP2 diet was significantly higher than those of fish fed OTC diet (P < 0.05). Nitro blue tetrazolium (NBT) activity and lysozyme activity of fish fed SP1, MP1 and MP2 diets were significantly higher than those of fish fed OTC diet (P < 0.05). However, there was no significant difference among fish fed SP1, SP2, MP1 and MP2 diets. During the Edwardsiella tarda challenge test, the first mortality occurred on day 2. After the 14 days challenge test, cumulative survival rate of fish fed MP1 and MP2 diets were significantly higher than those of fish fed control diet (P < 0.05). However, there was no significant difference among fish fed SP1, SP2, MP1, MP2 and OTC diets in survival rate at the termination of the challenge test. Although there was little advantage in immunological parameters with fish fed MP diets, single and multi-probiotics were equally effective statistically. These results demonstrated that single or multi-probiotics had equal beneficial effect as an antibiotic replacer in terms of growth performance, non-specific immune responses and disease resistance in starry flounder.

Effects of Korean red ginseng extracts on neural tube defects and impairment of social interaction induced by prenatal exposure to valproic acid.

Ginseng is one of the most widely used medicinal plants, which belongs to the genus Panax. Compared to uncured white ginseng, red ginseng has been generally regarded to produce superior pharmacological effects with lesser side/adverse effects, which made it popular in a variety of formulation from tea to oriental medicine. Using the prenatal valproic acid (VPA)-injection model of autism spectrum disorder (ASD) in rats, which produces social impairrment and altered seizure susceptibility as in human ASD patients as well as mild neural tube defects like crooked tail phenotype, we examined whether chronic administration of red ginseng extract may rescue the social impairment and crooked tail phenotype in prenatally VPA-exposed rat offspring. VPA-induced impairment in social interactions tested using sociability and social preference paradigms as well as crooked tail phenotypes were significantly improved by administration of Korean red ginseng (KRG) in a dose dependent manner. Rat offspring prenatally exposed to VPA showed higher sensitivity to electric shock seizure and increased locomotor activity in open-field test. KRG treatment reversed abnormal locomotor activity and sensitivity to electric shock to control level. These results suggest that KRG may modulate neurobehavioral and structural organization of nervous system adversely affected by prenatal exposure to VPA.

Combination of initial stimulation thyroglobulins and staging system by revised ATA guidelines can elaborately discriminate prognosis of patients with differentiated thyroid carcinoma after high-dose remnant ablation.

PURPOSE: The aim of this study was to evaluate prognostic role of thyroglobulin (Tg) levels at the time of ablation (A-Tg) and stimulation Tg levels at 6-12 months after remnant ablation (S-Tg) combined with revised American Thyroid Association (ATA) guidelines risk stratification. PATIENTS AND METHODS: Data of 359 patients (median follow-up duration: 66.3 months) with papillary thyroid carcinoma who had high-dose remnant ablation were analyzed. The cutoff value of A-Tg to predict the persistent/recurrent disease was calculated by receiver operating characteristic curve analysis. In each risk group by ATA guidelines, the association of A-Tg with persistent/recurrent disease was evaluated. The role of A-Tg and ATA risk stratification in each S-Tg group (group with S-Tg <2 ng/mL, 2-10 ng/mL, or >10 ng/mL) was also evaluated. Tg response was determined by the difference between A-Tg and S-Tg with consideration of the dose of radioactive iodine ablation. RESULTS: A-Tg above 5.22 ng/mL was associated with persistent/recurrent disease in all risk groups by ATA guidelines. A-Tg above the cutoff value and ATA risk assessment was related to persistent/recurrent disease in patients with S-Tg 2 to 10 ng/mL (P = 0.003) and S-Tg above 10 ng/mL (P = 0.019). However, no difference in the incidence of persistent/recurrent disease was found according to Tg response. The scoring system made up of A-Tg, S-Tg, and ATA staging showed elaborate discrimination of prognosis. CONCLUSION: Risk stratification using combined scoring with initial stimulated Tg levels, including A-Tg and S-Tg, and staging system by revised ATA guidelines can effectively predict persistent/recurrent disease in patients with papillary thyroid carcinoma.

Role of [(18)F]-fluorodeoxy-D-glucose positron emission tomography and computed tomography in the early detection of persistent/recurrent thyroid carcinoma in intermediate-to-high risk patients following initial radioactive iodine ablation therapy.

BACKGROUND: Positron emission tomography/computed tomography (PET/CT) scan has a role in the surveillance of patients with a history of thyroid carcinoma. Its efficacy after remnant ablation as far as detecting persistent or recurrent thyroid carcinoma before other surveillance methods is not known, however. In intermediate-to-high risk thyroid carcinoma patients we studied whether PET/CT scan, performed 6-12 months after the first remnant ablation, could provide more information than ultrasonography (US) and thyrotropin-stimulated serum thyroglobulin (Tg) determination with diagnostic whole-body scan (DxWBS). METHODS: We studied 71 subjects with differentiated thyroid cancer (DTC) who were intermediate-to-high risk for persistent/recurrent disease and who had received PET/CT scan, US, and DxWBS simultaneously with stimulated Tg levels 6-12 months after remnant ablation. To evaluate the diagnostic efficacy of PET/CT scan, the sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy were calculated. RESULTS: Ten subjects (14%) had persistent/recurrent disease detected 6-12 months after remnant ablation. Persistence/recurrence was detected in nine (12.7%) of these patients by conventional methods, including US and DxWBS, along with stimulated Tg levels. The remaining case was detected solely by a PET/CT scan, which showed a mediastinal prevascular lesion; this was confirmed by a therapeutic WBS after additional radioiodine therapy. Among the six patients whose PET/CT scan showed positive results, five had persistent/recurrent disease. The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of PET/CT scan for detecting persistent/recurrent thyroid carcinoma were 50%, 98.4%, 83.3%, 92.3%, and 91.5%, respectively. CONCLUSION: In intermediate-to-high risk patients with DTC seen 6-12 months after their first remnant ablation, there is almost no complementary role for adding a PET/CT scan to conventional follow-up methods, an US and a DxWBS simultaneously with stimulated Tg levels.

SP-8203 shows neuroprotective effects and improves cognitive impairment in ischemic brain injury through NMDA receptor.

The extracts of earth worms, Eisenia andrei, have been used as a therapeutic agent for stroke in the traditional medicine. It is also reported that the protease fraction separated from the extracts has strong anti-thrombotic activity. Besides anti-thrombotic actions, we found that SP-8203, N-[3-(2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)propyl]-N-{4-[3-(2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)propylamino]butyl}acetamide, derived from the extracts of earth worms blocked N-methyl-(D)-aspartate (NMDA) receptor-mediated excitotoxicity in a competitive manner. The neuroprotective effects of SP-8203 were attributable to prevention of Ca(2+) influx through NMDA receptors. The systemic administration of SP-8203 markedly reduced neuronal death following middle cerebral artery occlusion in rats. SP-8203 significantly improved spatial learning and memory in the water maze test. These results provided strong pharmacological basis for its potential therapeutic roles in cerebral ischemia.

Striatal neurons expressing full-length mutant huntingtin exhibit decreased N-cadherin and altered neuritogenesis.

The expanded CAG repeat that causes striatal cell vulnerability in Huntington's disease (HD) encodes a polyglutamine tract in full-length huntingtin that is correlated with cellular [ATP] and [ATP/ADP]. Since striatal neurons are vulnerable to energy deficit, we have investigated, in Hdh CAG knock-in mice and striatal cells, the hypothesis that decreased energetics may affect neuronal (N)-cadherin, a candidate energy-sensitive adhesion protein that may contribute to HD striatal cell sensitivity. In vivo, N-cadherin was sensitive to ischemia and to the effects of full-length mutant huntingtin, progressively decreasing in Hdh(Q111) striatum with age. In cultured striatal cells, N-cadherin was decreased by ATP depletion and STHdh(Q111) striatal cells exhibited dramatically decreased N-cadherin, due to decreased Cdh2 mRNA and enhanced N-cadherin turnover, which was partially normalized by adenine supplementation to increase [ATP] and [ATP/ADP]. Consistent with decreased N-cadherin function, STHdh(Q111) striatal cells displayed profound deficits in calcium-dependent N-cadherin-mediated cell clustering and cell-substratum adhesion, and primary Hdh(Q111) striatal neuronal cells exhibited decreased N-cadherin and an abundance of immature neurites, featuring diffuse, rather than clustered, staining for N-cadherin and synaptic vesicle markers, which was partially rescued by adenine treatment. Thus, mutant full-length huntingtin, via energetic deficit, contributes to decreased N-cadherin levels in striatal neurons, with detrimental effects on neurite maturation, strongly suggesting that N-cadherin-mediated signaling merits investigation early in the HD pathogenic disease process.

Thalamic changes in temporal lobe epilepsy with and without hippocampal sclerosis: a diffusion tensor imaging study.

OBJECTIVE: The seizure network may be different between temporal lobe epilepsy with hippocampal sclerosis (TLE+HS) and without HS (TLE-HS). Chronic seizure activity may alter the diffusion properties of a seizure network. The thalamus is known to have an anatomical connection to the medial temporal area and to play a role in seizure modulation. This study aimed to evaluate differences in thalamic changes between TLE+HS and TLE-HS with diffusion tensor imaging (DTI). METHODS: Nine patients with TLE+HS and nine patients with TLE-HS were included in the study. All patients underwent surgery with good seizure outcomes. Hippocampal sclerosis was verified pathologically. Sixteen right-handed, normal subjects were enrolled as controls. DTI was acquired using 3.0 T MRI. The mean diffusivity (MD) and fractional anisotropy (FA) were calculated in the center of the bilateral thalamus with the DTIstudio program. RESULTS: The MD of bilateral thalami increased in both TLE groups compared to controls (p<0.05), while FA values did not differ from controls. The MD of the thalamus ipsilateral to the epileptogenic side was higher in the TLE+HS group than in the TLE-HS group (p=0.007). Onset age, seizure duration, seizure frequency and total seizure number were not correlated with FA and MD changes (p>0.05). CONCLUSION: Bilateral thalamic diffusion properties are altered in temporal lobe epilepsy. The presence of hippocampal sclerosis enhances the change ipsilaterally.

Intakes of vitamin A, C, and E, and beta-carotene are associated with risk of cervical cancer: a case-control study in Korea.

Cervical cancer is one of the most common gynecological malignancies in Korea, although the incidence has been declining in recent years. This study explored whether antioxidant vitamin intakes influenced the risk of cervical cancer. The association between antioxidant vitamin intakes and cervical cancer risk was calculated for 144 cervical cancer cases and 288 age-matched, hospital-based controls using unconditional logistic regression models. Cases reported statistically lower mean dietary intakes of vitamin A, beta -carotene, and vitamin C than did controls. Total intakes of vitamins A and E, which included both dietary and supplement intake, were also lower in cases. Those patients in the highest quartiles of dietary vitamin A, beta -carotene, and vitamin C intakes had statistically significantly lower cervical cancer risks than those in the lowest quartiles for vitamin A, beta -carotene, and vitamin C: odds ratio (OR) = 0.36 [95% confidence interval (CI) = 0.19-0.69), OR = 0.48 (CI = 0.26-0.88), and OR = 0.36 (CI = 0.18-0.69), respectively. Total intakes of vitamins A, C, and E were strongly inversely associated with cervical cancer risk: OR = 0.35 (CI = 0.19-0.65), OR = 0.35 (CI = 0.19-0.66), and OR = 0.53 (CI = 0.28-0.99), respectively. The findings support a role for increased antioxidant vitamin intake in decreasing the risk of cervical cancer. These associations need to be assessed in large prospective studies with long-term follow-up.

Integration of cross-modal emotional information in the human brain: an fMRI study.

The interaction of information derived from the voice and facial expression of a speaker contributes to the interpretation of the emotional state of the speaker and to the formation of inferences about information that may have been merely implied in the verbal communication. Therefore, we investigated the brain processes responsible for the integration of emotional information originating from different sources. Although several studies have reported possible sites for integration, further investigation using a neutral emotional condition is required to locate emotion-specific networks. Using functional magnetic resonance imaging (fMRI), we explored the brain regions involved in the integration of emotional information from different modalities in comparison to those involved in integrating emotionally neutral information. There was significant activation in the superior temporal gyrus (STG); inferior frontal gyrus (IFG); and parahippocampal gyrus, including the amygdala, under the bimodal versus the unimodal condition, irrespective of the emotional content. We confirmed the results of previous studies by finding that the bimodal emotional condition elicited strong activation in the left middle temporal gyrus (MTG), and we extended this finding to locate the effects of emotional factors by using a neutral condition in the experimental design. We found anger-specific activation in the posterior cingulate, fusiform gyrus, and cerebellum, whereas we found happiness-specific activation in the MTG, parahippocampal gyrus, hippocampus, claustrum, inferior parietal lobule, cuneus, middle frontal gyrus (MFG), IFG, and anterior cingulate. These emotion-specific activations suggest that each emotion uses a separate network to integrate bimodal information and shares a common network for cross-modal integration.

Proton magnetic resonance spectroscopy in subjects with high genetic risk of schizophrenia: investigation of anterior cingulate, dorsolateral prefrontal cortex and thalamus.

OBJECTIVE: Reduced N-acetylaspartate levels in regions of the frontal cortex, including the anterior cingulate cortex, dorsolateral prefrontal cortex, and thalamus, involved in the pathophysiology of schizophrenia suggest that brain metabolite abnormalities may be a marker of genetic vulnerability to schizophrenia. We used proton magnetic resonance spectroscopy (H-MRS) to acquire absolute concentrations of brain metabolites in subjects with a high genetic risk of schizophrenia to investigate the potential relationship between unexpressed genetic liability to schizophrenia and neuronal dysfunction. METHOD: Included in the study were 22 subjects who had at least two relatives with schizophrenia (high genetic risk group) and 22 controls with no second-degree relatives with schizophrenia. Absolute concentrations of N-acetylaspartate, creatine, choline, glutamate/glutamine, and myo-inositol and the ratios of metabolites in the anterior cingulate cortex, left dorsolateral prefrontal cortex, and left thalamus were measured using H-MRS at 1.5 Tesla. RESULTS: Relative to the controls, the high genetic risk group showed significant differences in absolute metabolite levels in the spectra of the regions of the left thalamus, including significant decreases in N-acetylaspartate, creatine, and choline concentrations. CONCLUSIONS: The study points to neuronal dysfunction, and in particular thalamic dysfunction, as a key region of the vulnerability marker of schizophrenia. Further studies should examine the nature of the thalamus more intensively to further our understanding of thalamic dysfunction as a vulnerability marker.