Synchrotron Analysis of Damaged Extraction Sockets Augmented Using a Synthetic Bone Block: A Pilot Study.

This study aimed to investigate the dimensional stability and quality of the alveolar ridge augmented using a synthetic bone block (SBB) at damaged extraction sockets. Four participants were included, and socket augmentation was performed using SBB and a collagen membrane. Intraoral and CBCT scans were performed before extraction (baseline), immediately postoperative (IP), and at 6 months postoperative (6M). At 6M, a trephine biopsy sample was obtained during implant placement, and the sample was observed using synchrotron. Soft tissue profile changes were assessed using profilometric analysis of the intraoral scan data, while dimensional changes in hard tissue were evaluated based on CBCT measurements. Bone quality was analyzed using synchrotron imaging. There were minimal changes in the soft tissue profile between baseline and IP, baseline and 6M, and IP and 6M (0.11 ± 1.08 mm3, 0.02 ± 0.8 mm3, and -0.65 ± 0.82 mm3, respectively). Horizontal bone width was measured at 1-mm increments from the augmented bone crest to 5 mm apically and revealed only a slight reduction (< 1 mm) at all levels between IP and 6M. The augmented bone height was well maintained from IP until 6M (-0.21 ± 0.53 mm). Synchrotron analysis revealed low to moderate bone quality after 6M (percentage of new bone: 16.49% ± 4.91%). Socket augmentation using SBB appears to be a viable technique for regenerating damaged extraction sockets, with the augmented ridge dimensions maintained up to 6M. Further long-term randomized clinical trials are needed.

Effect of 4-week preoperative prism adaptation in preventing postoperative residual esotropia.

BACKGROUND: Preoperative prism adaptation (PPA) simulates postoperative status and possibly can predict postoperative undercorrection before surgery in esotropia. The present study aimed to assess the effect of 4-week PPA in preventing postoperative residual esotropia. METHODS: Seventy-five (75) esotropes who had undergone surgery at a single strabismus center were retrospectively enrolled. They included 25 basic, 31 acute comitant, 10 partially accommodative, and 9 recurrent esotropia patients. The preoperative deviation angle, which had been determined using the alternating prism and cover test, was fully corrected with press-on prisms 4 weeks before surgery. If there was an increase of 5 PD or more of esodeviation, the prisms were changed accordingly at 2 weeks. The deviation angle measured at 4 weeks was determined as the surgical target angle. Patients were then divided into increase (≥ 5 PD increase of angle during 4-week PPA) and non-increase groups. Success was defined as either esodeviation of 8 PD or under or exodeviation of 5 PD or under at distance at postoperative 6 months. RESULTS: The increase group included 44 patients (58.7%). The mean deviation angle before PPA was 27.4 PD, and after the 4-week PPA, there was an average increase of 9.4 PD. The success rate was 90.9% in the increase group and 96.8% in the non-increase group (p = 0.316). There were no intergroup differences in preoperative clinical characteristics, esotropia types, postoperative deviation angle or postoperative near stereopsis (p > 0.05). CONCLUSIONS: The results of this study indicated a beneficial effect of 4-week PPA in esotropia of various types, specifically by uncovering the hidden esodeviation in the increase group and simulating the postoperative alignment in both the increase and the non-increase groups.

Risk of post-operative bleeding after dentoalveolar surgery in patients taking anticoagulants: a cohort study using the common data model.

This retrospective study aimed to determine risk factors associated with post-operative bleeding after dentoalveolar surgery in patients taking anticoagulants. Patients taking anticoagulants who were planned to undergo periodontal flap operation, tooth extraction or implant surgery were included. Patients were divided into two subgroups according to the maintenance of anticoagulants following medical consultation: (1) maintenance group and (2) discontinuation group. The analysed patient-related factors included systemic diseases, maintenance of anticoagulants and types of anticoagulant. Intra- and post-operative treatment-related factors, haemostatic methods and post-operative bleeding were collected for statistical analyses. There were 35 post-operative bleeding complications (6.5%) in the 537 included patients: 21 (8.6%) in maintenance group and 14 (4.8%) in discontinuation group. The type of anticoagulant (p = 0.037), tooth extraction combined with bone grafting (p = 0.016) and type of implant surgery (p = 0.032) were significantly related to the post-operative bleeding rate. In the maintenance group, atrial fibrillation [odds ratio (OR) = 6.051] and vitamin K inhibitors (OR = 3.679) were associated with a significantly higher bleeding risk. From this result, it can be inferred that the decision to continue anticoagulants should be made carefully based on the types of anticoagulant and the characteristics of dentoalveolar surgeries performed: extraction with bone grafting, multiple implantations and involvement of maxillary arch.

The Antioxidant and Anti-Inflammatory Properties of Merremia umbellata Extract.

Merremia umbellata Hallier f. (MU) has been used as an anti-inflammatory agent to treat burns and scales. However, the potential anti-inflammatory mechanisms of action of this plant have not been elucidated. This study aimed to assess the antioxidant and anti-inflammatory effects of the leaf and shoot of MU grown in Bangladesh. The MU extract exhibited antioxidant activities as demonstrated by DPPH and ABTS free-radical-scavenging activities and the total polyphenol and total flavonoid contents. MU extract significantly reduced the lipopolysaccharide (LPS)-stimulated nitric oxide (NO) production in RAW264.7 macrophage. Accordingly, the gene levels of inducible NO synthase and cyclooxygenase-2 were suppressed. The MU extract alleviated the LPS-induced expression of TLR4, NF-κB, and inflammatory cytokines (TNF-α, IL-6, and IL-1ß). The constituents of a MU extract were tentatively identified using UHPLC-PDA-QTOF/MS techniques. The main compounds were identified as 3,4-dicaffeoylquinic acid, 3,5-dicaffeoylquinic acid, quercitrin, and 4,5-dicaffeoylquinic acid. Molecular docking analysis revealed that these compounds interact with TLR4 protein, with quercitrin showing the highest binding affinity among them. Overall, our findings demonstrate the antioxidant and in vitro anti-inflammatory activities of MU and its potential compounds to target the TLR4-NF-κB signaling pathway. These findings are potentially used to further explore promising natural food ingredients that are effective in regulating inflammation.

Virological characteristics and the rapid antigen test as deisolation criteria in immunocompromised patients with COVID-19: A prospective cohort study.

There are limited data supporting current Centers for Disease Control and Prevention guidelines for the isolation period in moderate to severely immunocompromised patients with coronavirus disease 2019 (COVID-19). Adult COVID-19 patients who underwent solid organ transplantation (SOT) or received active chemotherapy against hematologic malignancy were enrolled and weekly respiratory samples were collected. Samples with positive genomic real-time polymerase chain reaction results underwent virus culture and rapid antigen testing (RAT). A total of 65 patients (40 with hematologic malignancy and 25 SOT) were enrolled. The median duration of viable virus shedding was 4 weeks (interquartile range: 3-7). Multivariable analysis revealed that B-cell depletion (hazard ratio [HR]: 4.76) was associated with prolonged viral shedding, and COVID-19 vaccination (≥3 doses) was negatively associated with prolonged viral shedding (HR: 0.22). The sensitivity, specificity, positive predictive value, and negative predictive value of RAT for viable virus shedding were 79%, 76%, 74%, and 81%, respectively. The negative predictive value of RAT was only 48% (95% confidence interval [CI]: 33-65) in the samples from those with symptom onset ≤20 days, but it was as high as 92% (95% CI: 85-96) in the samples from those with symptom onset >20 days. About half of immunocompromised COVID-19 patients shed viable virus for ≥4 weeks from the diagnosis, and virus shedding was prolonged especially in unvaccinated patients with B-cell-depleting therapy treatment. RAT beyond 20 days in immunocompromised patients had a relatively high negative predictive value for viable virus shedding.

Application of Milk Exosomes for Musculoskeletal Health: Talking Points in Recent Outcomes.

Milk is a nutrient-rich food source, and among the various milks, breast milk is a nutrient source provided by mothers to newborns in many mammals. Exosomes are nano-sized membranous extracellular vesicles that play important roles in cell-to-cell communication. Exosomes originate from endogenous synthesis and dietary sources such as milk. Discovered through electron microscopy as floating vesicles, the existence of exosomes in human milk was confirmed owing to a density between 1.10 and 1.18 g/mL in a sucrose gradient corresponding to the known density of exosomes and detection of MHC classes I and II, CD63, CD81, and CD86 on the vesicles. To date, milk exosomes have been used for treating many diseases, including cancers, and are widely proposed as promising carriers for the delivery of chemotherapeutic agents. However, few studies on milk exosomes focus on geriatric health, especially sarcopenia and osteoporosis related to bone and muscle. Therefore, the present study focused on milk exosomes and their cargoes, which are potential candidates for dietary supplements, and when combined with drugs, they can be effective in treating musculoskeletal diseases. In this review, we introduce the basic concepts, including the definition, various sources, and cargoes of milk exosomes, and exosome isolation and characterization methods. Additionally, we review recent literature on the musculoskeletal system and milk exosomes. Since inflammation and oxidative stress underly musculoskeletal disorders, studies reporting the antioxidant and anti-inflammatory properties of milk exosomes are also summarized. Finally, the therapeutic potential of milk exosomes in targeting muscle and bone health is proposed.

Synchrotron Analysis of Damaged Extraction Sockets Augmented Using a Synthetic Bone Block: A Pilot Study.

AIM: To investigate the dimensional stability and quality of the alveolar ridge augmented using a synthetic bone block (SBB) at damaged extraction sockets. MATERIALS AND METHODS: Four participants were included in whom socket augmentation was performed using SBB and a collagen membrane. Intraoral scan (IOS) was performed before extraction (baseline), immediately postoperative (IP), and at 6 months (6M). Cone-beam computed tomography (CBCT) was performed at IP and 6M. At 6M, a trephine biopsy was obtained during implant placement and the sample was observed using synchrotron. Profilometric change of soft tissue was measured from the IOS data, hard tissue dimensional change was measured from the CBCT data and the bone quality from synchrotron data. RESULTS: There were minimal changes in the soft tissue profile between baseline and IP, baseline and 6M, and IP and 6M (0.11±1.08 and 0.02±0.8, and -0.65±0.82 mm3). Horizontal bone width measured at 1 mm increments from the augmented bone crest to 5 mm apically revealed only slight reduction (less than 1 mm) at all levels between IP and 6M. The augmented bone height was well maintained from IP until 6M (-0.21±0.53 mm). Synchrotron analysis revealed low to moderate bone quality after 6M (percentage new bone = 16.49±4.91). CONCLUSIONS: Augmentation of the damaged extraction socket using SBB is a viable technique, in which the dimensions of the augmented ridge can be maintained up to 6M. Further long term randomized clinical trial is needed.

Heterologous vaccination utilizing viral vector and protein platforms confers complete protection against SFTSV.

Severe fever with thrombocytopenia syndrome virus was first discovered in 2009 as the causative agent of severe fever with thrombocytopenia syndrome. Despite its potential threat to public health, no prophylactic vaccine is yet available. This study developed a heterologous prime-boost strategy comprising priming with recombinant replication-deficient human adenovirus type 5 (rAd5) expressing the surface glycoprotein, Gn, and boosting with Gn protein. This vaccination regimen induced balanced Th1/Th2 immune responses and resulted in potent humoral and T cell-mediated responses in mice. It elicited high neutralizing antibody titers in both mice and non-human primates. Transcriptome analysis revealed that rAd5 and Gn proteins induced adaptive and innate immune pathways, respectively. This study provides immunological and mechanistic insight into this heterologous regimen and paves the way for future strategies against emerging infectious diseases.

Low-dose curcumin enhances hippocampal neurogenesis and memory retention in young mice.

Adult neurogenesis generates new functional neurons from adult neural stem cells in various regions, including the subventricular zone (SVZ) of the lateral ventricles and subgranular zone (SGZ) of hippocampal dentate gyrus (DG). Available evidence shows hippocampal neurogenesis can be negatively or positively regulated by dietary components. In a previous study, we reported that curcumin (diferuloylmethane; a polyphenolic found in curry spice) stimulates the proliferation of embryonic neural stem cells (NSCs) by activating adaptive cellular stress responses. Here, we investigated whether subchronic administration of curcumin (once daily at 0.4, 2, or 10 mg/kg for 14 days) promotes hippocampal neurogenesis and neurocognitive function in young (5-week-old) mice. Oral administration of low-dose curcumin (0.4 mg/kg) increased the proliferation and survival of newly generated cells in hippocampus, but surprisingly, high-dose curcumin (10 mg/kg) did not effectively upregulate the proliferation or survival of newborn cells. Furthermore, hippocampal BDNF levels and phosphorylated CREB activity were elevated in only low-dose curcumin-treated mice. Passive avoidance testing revealed that low-dose curcumin increased cross-over latency times, indicating enhanced memory retention, and an in vitro study showed that low-concentration curcumin increased the proliferative activity of neural progenitor cells (NPCs) by upregulating NF1X levels. Collectively, our findings suggest that low-dose curcumin has neurogenic effects and that it may prevent age and neurodegenerative disease-related cognitive deficits.

Vertical and horizontal ridge augmentation using customized three-dimensionally printed polycaprolactone mesh in atrophic posterior maxillae: a case report.

Polycaprolactone has exhibited expediency as a biomaterial for bone regenerative procedures preclinically. The present report of the two clinical cases in the posterior maxilla is the first to describe clinical application of a customized 3D printed polycaprolactone mesh for alveolar ridge augmentation. Two patients needing extensive ridge augmentation procedures for dental implant therapy were selected. Polycaprolactone meshes were virtually designed, 3D printed and applied in combination with a xenogeneic bone substitute. Cone-beam computed tomography was taken pre-operatively, immediately after the surgery, and 1.5 to 2 years after the delivery of implant prostheses. The serial cone-beam computed tomography images were superimposed to measure the augmented height and width at 1 mm increments from the implant platform to 3 mm apically. After 2 years, the mean [maximum, minimum] bone gain was 6.05 [8.64, 2.85] mm vertically and 7.77 [10.03, 6.18] mm horizontally at 1 mm below the implant platform. From immediately postoperative to 2 years, there was 14 % reduction of augmented ridged height and 24 % reduction of augmented width at 1 mm below the platform. All implants placed in augmented sites were successfully maintained until 2 years. The customized Polycaprolactone mesh might be a viable material for ridge augmentation in the atrophic posterior maxilla. This needs to be confirmed through randomized controlled clinical trials in future studies.

Clinical relevance of thyroid-stimulating immunoglobulin as a biomarker of the activity of thyroid eye disease.

BACKGROUND/OBJECTIVES: Although it has been reported that thyroid-stimulating immunoglobulin (TSI) is associated with the clinical characteristics of thyroid eye disease (TED), there is a paucity of literature regarding the role of TSI in diagnosing active TED. This study investigated the relationship between the level of TSI and the activity of TED and assessed the cut-off value of TSI discriminating active TED from inactive TED. METHODS: This cross-sectional study included 101 patients with TED. TSI was quantitatively measured with a cell-based bioassay using a chimeric TSH receptor and a cyclic adenosine monophosphate response element-dependent luciferase. The association between TSI and a variety of demographic and clinical features of TED was analysed. Multivariate regression analysis was performed to determine possible independent factors affecting the level of TSI. RESULTS: TSI level was higher in males than in females (p = 0.023) and smokers than in nonsmokers (p = 0.004). TSI level was inversely correlated with the duration of ocular symptoms (r = -0.295, p = 0.003). The level of TSI was also significantly different when compared to the thyroid function (p = 0.003), TED activity (p < 0.001), and TED severity (p = 0.001). Multivariate regression analysis revealed a significant relationship between TED activity and thyroid function jointly and the TSI level. The cut-off level of TSI for predicting active TED was a specimen-to-reference ratio of 406.7 (p < 0.001, area under the curve = 0.847, sensitivity 77.4%, specificity 81.3%). CONCLUSIONS: TSI was a functional biomarker strongly associated with TED activity even after being adjusted by other clinical characteristics. Serum TSI level may help identify patients with active TED in clinics.

Microglial response in triggering receptor expressed on myeloid cells 2 (TREM2) knock-out mice after systemic stimulation with Escherichia coli.

BACKGROUND: Systemic infection is an important risk factor for delirium, associated with neurodegeneration and subsequent cognitive impairment in older people. Microglial cell response is a known key player in this process and we hypothesize that the triggering receptor expressed on myeloid cells 2 (TREM2) plays an important role in the regulation of this response. METHODS: 8- to 10-week old male wild-type (WT) and TREM2 knock-out (Trem2-/-) mice were intraperitoneally inoculated with live Escherichia coli (E. coli) or saline. After inoculation, all mice were treated with ceftriaxone (an antimicrobial drug) at 12 and 24 h and were sacrificed after 2 and 3 days. Microglial response was determined by immunohistochemical staining with an ionized calcium-binding adaptor molecule 1 (Iba-1) antibody and flow cytometry. mRNA expression of pro- and anti-inflammatory mediators was measured to quantify the inflammatory response. RESULTS: We observed increased Iba-1 positive cells number in thalamus of Trem2-/- mice at 3d after inoculation compared to WT mice (mean 120 cell/mm2 [SD 8] vs 105 cell/mm2 [SD 11]; p = 0.03). Flow cytometry showed no differences in forward scatter or expression of CD11b, CD45 and CD14 between WT and Trem2-/- mice. The brain mRNA expression levels of tumor necrosis factor alpha (TNF-α) of Trem2-/- mice at 2d were higher compared to WT mice (p = 0.003). Higher mRNA expression of interleukin 1 beta (IL-1ß), Iba-1, CD11b and mitogen-activated protein kinase 1 (MAPK-1) was found in brain of WT mice at 2d compared to Trem2-/- mice (respectively p = 0.02; p = 0.001; p = 0.03 and p = 0.02). In spleen there were no differences in inflammatory mediators, between WT and Trem2-/- mice. INTERPRETATION: Although the loss of function of TREM2 during systemic infection led to an increased number of activated microglia in the thalamus, we did not observe a consistent increase in expression of inflammatory genes in the brain. The role of TREM2 in the neuro-inflammatory response following systemic infection therefore appears to be limited.

Microglial cell response in α7 nicotinic acetylcholine receptor-deficient mice after systemic infection with Escherichia coli.

BACKGROUND: Development of neurodegeneration in older people has been associated with microglial cell activation triggered by systemic infection. We hypothesize that α7 nicotinic acetylcholine receptor (α7nAChR) plays an important role in regulation of this process. METHODS: 8- to 10-week-old male wild-type (WT) and α7nAChR knock-out (α7nAChR-/-) mice were intraperitoneally inoculated with live Escherichia (E.) coli or saline. After inoculation, all mice were treated with ceftriaxone (an antimicrobial drug) at 12 and 24 h and killed at 2 or 3 days. The microglial response was characterized by immunohistochemical staining with an ionized calcium-binding adaptor molecule 1 (Iba-1) antibody and flow cytometry. To quantify inflammatory response, mRNA expression of pro- and anti-inflammatory mediators was measured in brain and spleen. RESULTS: We observed no differences in Iba-1 positive cell number or morphology and flow cytometry (CD11b, CD45 and CD14) of microglial cells between WT and α7nAChR-/- mice after systemic infection. Infected α7nAChR-/- mice showed significantly higher mRNA expression in brain for tumor necrosis factor alpha (TNF-α) at day 2 and 3, interleukin 6 (IL-6) at day 2 and monocyte chemotactic protein 1 (MCP-1) and suppressor of cytokine signaling 1 (SOCS1) at day 3, there was significantly lower mRNA expression in brain for mitogen-activated protein kinase 1 (MAPK1) at day 2 and 3, high-mobility group 1 (HMGB-1) and CD11b at day 2, and deubiquitinase protein A20 (A20) at day 3 compared to infected WT mice. INTERPRETATION: Loss of function of α7nAChR during systemic infection led to an increased expression of TNF-α and IL-6 in brain after systemic infection with E. coli, but not to distinct differences in microglial cell number or morphological activation of microglia.

Nasal packing with Merocel in a glove finger after endoscopic endonasal reduction of medial blowout fracture.

ABSTRACT: After endoscopic endonasal reduction (EER) for medial blowout fracture (BOF), nasal packing may be necessary for sustaining the reduced orbital contents. This study aimed to introduce a new packing technique using Merocel in a glove finger.We retrospectively reviewed 131 patients with a mean age of 42.2 years (range, 13-80 years), who underwent EER for medial BOF, followed by a postoperative nasal packing of Merocel in a glove finger, between March 2016 and December 2019. Sex, age, side and cause of trauma, pre-operative diplopia and enophthalmos, duration from the occurrence of trauma to surgery, postoperative diplopia, enophthalmos, complications like sinusitis, and revision surgery were evaluated.The most common cause of injury was physical assault in 47 cases and a fall or slip event in 34. Pre-operatively 22 patients had diplopia and 1 patient had enophthalmos. Mean duration after trauma to the surgery was 13.2 days (range, 1-29 days). The mean operative time was 34.1 minutes (range, 10-70 minutes). Four weeks after operation, the nasal packing was removed at an outpatient clinic, with minimal pain, discomfort, and bleeding and no evidence of infection or inflammation. A computed tomography scan performed at 3 months postoperatively showed no re-bulging. The computed tomography image of 1 patient showed frontal sinus haziness; the patient had a headache and underwent endoscopic sinus surgery for symptomatic relief. Three patients had diplopia and 1 had enophthalmos at final follow-up. No other major postoperative complications were noted.Merocel in a glove finger packing technique proved itself to be safe and effective after EER for medial BOF.

Cortisol induces follicle regression, while FSH prevents cortisol-induced follicle regression in pigs.

During follicular development, a few dominant follicles develop to large antral dominant follicles, whereas the remaining follicles undergo atretic degeneration. Because vascularization on the follicular surface is a morphological feature of dominant follicles, we previously classified these follicles as vascularized follicles (VFs) and non-VFs (NVFs). In NVFs, progesterone producing genes were expressed similarly to that in VFs; however, the progesterone concentration in follicular fluid was low in large NVFs. Therefore, we estimated that progesterone is converted to cortisol, which induces the loss of follicular functions. In this study, we comparative analyzed the expression of genes for progesterone converting enzymes (Cytochrome (CYP)11B1, CYP21A2, Hydroxysteroid (HSD)11B2) and cortisol receptor (NR3C1) in VF and NVF granulosa cells. In NVFs, expression of cortisol producing genes (CYP11B1 and CYP21A2) was higher than in VFs. Expression of the gene for the cortisol metabolizing enzyme HSD11B2 in NVFs was significantly lower than in VFs. In NVFs, accompanied by increasing cortisol concentration in follicular fluid, apoptosis of granulosa and cumulus cells was observed. Cultivation with FSH and metyrapone (a CYP11B1 inhibitor) of NVF cumulus-oocyte complexes inhibited apoptosis of cumulus cells and induced cumulus cell proliferation and oocyte maturation. Cortisol-induced CYP11B1 and CYP21A2 expression, whereas FSH-induced HSD11B2 mRNA expression in VF granulosa cells in the presence of cortisol. Furthermore, an addition of 18ß-glycyrrhetinic acid (18-GA; a HSD17B2 inhibitor) to cortisol and FSH-containing medium increased apoptosis of VF granulosa cells. These results suggested that cortisol is a stimulatory factor that induces follicular atresia; furthermore, inhibition of cortisol production by FSH might increase the number of healthy preovulatory follicles in pigs.

The incidence and presumed aetiologies of fourth cranial nerve palsy in Korea: a 10-year nationwide cohort study.

AIMS: To investigate the incidence and presumed aetiologies of fourth cranial nerve (CN4) palsy in Korea METHODS: Using the nationally representative dataset of the Korea National Health Insurance Service-National Sample Cohort from 2006 to 2015, newly developed CN4 palsy cases confirmed by a preceding disease-free period of ≥4 years were identified. The presumed aetiology of CN4 palsy was evaluated based on comorbidities around the CN4 palsy diagnosis. RESULTS: Among the 1,108,292 cohort subjects, CN4 palsy newly developed in 390 patients during 10-year follow-up, and the overall incidence of CN4 palsy was 3.74 per 100,000 person-years (95% confidence interval, 3.38-4.12). The incidence of CN4 palsy showed a male preponderance in nearly all age groups, and the overall male-to-female ratio was 2.30. A bimodality by age-group was observed, with two peaks at 0-4 years and at 75-79 years. The most common presumed aetiologies were vascular (51.3%), congenital (20.0%), and idiopathic (18.5%). The incidence rate of a first peak for 0-4 years of age was 6.17 per 100,000 person-years, and cases in this group were congenital. The second peak incidence rate for 75-79 years of age was 11.81 per 100,000 person-years, and the main cause was vascular disease. Strabismus surgery was performed in 48 (12.3%) patients, most of whom (72.9%) were younger than 20 years. CONCLUSION: The incidence of CN4 palsy has a male predominance in Koreans and shows bimodal peaks by age. The aetiology of CN4 palsy varies according to age-groups.

Targeting a Lipid Desaturation Enzyme, SCD1, Selectively Eliminates Colon Cancer Stem Cells through the Suppression of Wnt and NOTCH Signaling.

The elimination of the cancer stem cell (CSC) population may be required to achieve better outcomes of cancer therapy. We evaluated stearoyl-CoA desaturase 1 (SCD1) as a novel target for CSC-selective elimination in colon cancer. CSCs expressed more SCD1 than bulk cultured cells (BCCs), and blocking SCD1 expression or function revealed an essential role for SCD1 in the survival of CSCs, but not BCCs. The CSC potential selectively decreased after treatment with the SCD1 inhibitor in vitro and in vivo. The CSC-selective suppression was mediated through the induction of apoptosis. The mechanism leading to selective CSC death was investigated by performing a quantitative RT-PCR analysis of 14 CSC-specific signaling and marker genes after 24 and 48 h of treatment with two concentrations of an inhibitor. The decrease in the expression of Notch1 and AXIN2 preceded changes in the expression of all other genes, at 24 h of treatment in a dose-dependent manner, followed by the downregulation of most Wnt- and NOTCH-signaling genes. Collectively, we showed that not only Wnt but also NOTCH signaling is a primary target of suppression by SCD1 inhibition in CSCs, suggesting the possibility of targeting SCD1 against colon cancer in clinical settings.

An infectious cDNA clone of a growth attenuated Korean isolate of MERS coronavirus KNIH002 in clade B.

The MERS-CoV isolated during the 2015 nosocomial outbreak in Korea showed distinctive differences in mortality and transmission patterns compared to the prototype MERS-CoV EMC strain belonging to clade A. We established a BAC-based reverse genetics system for a Korean isolate of MERS-CoV KNIH002 in the clade B phylogenetically far from the EMC strain, and generated a recombinant MERS-CoV expressing red fluorescent protein. The virus rescued from the infectious clone and KNIH002 strain displayed growth attenuation compared to the EMC strain. Consecutive passages of the rescued virus rapidly generated various ORF5 variants, highlighting its genetic instability and calling for caution in the use of repeatedly passaged virus in pathogenesis studies and for evaluation of control measures against MERS-CoV. The infectious clone for the KNIH002 in contemporary epidemic clade B would be useful for better understanding of a functional link between molecular evolution and pathophysiology of MERS-CoV by comparative studies with EMC strain.

A Potential Approach to Compensate the Gas Interference for the Analysis of NO by a Non-dispersive Infrared Technique.

Interference is a pivotal issue of a non-dispersive infrared (NDIR) sensor and analyzer. Therefore, the main contribution of this study is to introduce a potential method to compensate for the interference of the NDIR analysis. A potential method to compensate for the interference of a nitric oxide (NO) NDIR analyzer was developed. Double bandpass filters (BPFs) with HITRAN (high-resolution transmission molecular absorption database)-based wavelengths were used to create an ultranarrow bandwidth, where there were least-interfering effects with respect to the coal-fired power plant emission gas compositions. Key emission gases from a coal-fired power plant, comprising carbon monoxide (CO), NO, sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon dioxide (CO2), and water (H2O) (in the form of vapor), were used to investigate the gas interference. The mixtures of those gases were also used to investigate the performance of the double BPFs. We found that CO, CO2, SO2, and H2O significantly affected the detection of NO when a commercial, single narrow BPF was used. In contrast, the double BPFs could remove the interference of CO, NO2, SO2, and CO2 in terms of their concentrations. In the case of H2O, the filter performed well until a level of 50% relative humidity at 25 °C. Moreover, the signal-to-noise ratio of the analyzer was approximately 10 when the double BPFs were applied. In addition, the limit of detection of the analyzer with the double BPFs was approximately 4 ppm, whereas that with the commercial one was 1.3 ppm. Therefore, double BPFs could be used for an NO NDIR analyzer instead of a gas filter correlation to improve the selectivity of the analyzer under the condition of a known gas composition, such as a coal-fired power plant. However, the sensitivity of the analyzer would be decreased.

Iron deficiency induces female infertile in order to failure of follicular development in mice.

Iron is important for many cellular functions, including ATP synthesis and cell proliferation. Insufficient of iron in the diet causes iron deficiency anemia (IDA), which often occurs in people living in the world. Since 50% of women with IDA show amenorrhea, the relationship of between iron deficiency and reproductive function was assessed using mice fed a low Fe diet (LFD). The estrous cycle in the LFD mice was blocked at diestrus, which impair follicle development, and fertility. Further, even LFD mice were injected with exogenous pregnant mare serum gonadotropin (PMSG), follicular development was ceased at the secondary follicle stage, and preovulatory follicles were not observed. Amount of ATP decreased in the ovary of the LFD mice, and expression of follicle development markers (Fshr, Cyp19a1, Ccnd2) and estradiol-17ß (E2) was low level compared to levels mice fed a normal diet. Feeding a normal diet with sufficient iron to the LFD mice for an additional 3 weeks completely reversed absence the effects of iron insufficient on the estrous cycle and infertility. Thus, iron restriction depresses ovary functions, especially follicular development from secondary follicle to antral follicles and infertility. These effects are fully reversible by supplementation of a normal diet containing iron.