Engineering homoeologs provide a fine scale for quantitative traits in polyploid.

Numerous staple crops exhibit polyploidy and are difficult to genetically modify. However, recent advances in genome sequencing and editing have enabled polyploid genome engineering. The hexaploid black nightshade species Solanum nigrum has immense potential as a beneficial food supplement. We assembled its genome at the scaffold level. After functional annotations, we identified homoeologous gene sets, with similar sequence and expression profiles, based on comparative analyses of orthologous genes with close diploid relatives Solanum americanum and S. lycopersicum. Using CRISPR-Cas9-mediated mutagenesis, we generated various mutation combinations in homoeologous genes. Multiple mutants showed quantitative phenotypic changes based on the genotype, resulting in a broad-spectrum effect on the quantitative traits of hexaploid S. nigrum. Furthermore, we successfully improved the fruit productivity of Boranong, an orphan cultivar of S. nigrum suggesting that engineering homoeologous genes could be useful for agricultural improvement of polyploid crops.

Psychopharmacological Considerations for Gender-Affirming Hormone Therapy.

ABSTRACT: The field of transgender health has grown exponentially since the early 2010s. While this increased visibility has not been without controversy, there is growing acknowledgement of the needs of transgender, nonbinary, and gender expansive (TNG) patients and the health disparities they experience compared to the cisgender population. There is also increased interest among clinicians and trainees in providing gender-affirming care in all medical specialties. This is particularly relevant in psychiatry as mental health disparities in TNG patients have been well-documented. TNG patients experience significant minority stress and higher rates of psychiatric illness, self-harm, suicidality, and psychiatric hospitalization compared to their cisgender peers. In this review, we will cover potential interactions and side effects relevant to psychiatric medication management for the three most common medication classes prescribed as part of gender-affirming hormone therapy (GAHT): gonadotropin-releasing hormone receptor agonists, estradiol, and testosterone. Although no studies directly examining the efficacy of psychiatric medications or their interactions with GAHT for TNG patients have been published yet, we have synthesized the existing literature from both cisgender and TNG patients to shed light on health care disparities seen in TNG patients. Since clinicians' lack of comfort and familiarity with gender-affirming care contributes significantly to these disparities, we hope this narrative review will help psychiatric prescribers provide TNG patients with the same quality of care that cisgender patients receive.

Nickel, cobalt, and chromium in nail sticker and tip products in Korea.

BACKGROUND: Nail stickers and nail tips are increasingly used nail products in Korea, and the rest of the world. However, no studies have examined if these specific consumer products might contain nickel, cobalt, and/or chromium, that is, metals known to provoke contact allergy. OBJECTIVE: We aimed to assess the release and content of nickel, cobalt, and chromium in nail stickers and tips by performing qualitative and quantitative analyses, respectively, of 50 convenience samples purchased in Korea. METHODS: Eighty-six qualitative spot tests were performed to determine the release of nickel, cobalt, and chromium on 35 nail stickers and 15 nail tips across five brands. Subsequently, the metal contents were quantified using inductively coupled plasma-optical mass spectrometry (ICP-MS). RESULTS: According to the spot tests, nickel was released in 7/86 (8.1%) tests before and 10/86 (11.6%) tests after exposure to artificial sweat. Cobalt and chromium (VI) spot test results were negative. However, ICP-MS detected nickel, cobalt, and chromium in 11%, 6.3%, and 16.7% of the samples, respectively. Detection rates were higher in nail tips than in stickers and were most common in rhinestones. CONCLUSION: Nail stickers and tips may contain nickel, cobalt, and/or chromium.

Androgen Receptor as a Predictive Marker for Pathologic Complete Response in Hormone Receptor-Positive and HER-2-Negative Breast Cancer with Neoadjuvant Chemotherapy.

PURPOSE: This study investigated pathological complete response (pCR) according to androgen receptor (AR) in breast cancer patients undergoing neoadjuvant chemotherapy and estimated the relationship between AR expression and clinicopathological factors. Materials and Methods: We identified 624 breast cancer patients who underwent surgery after neoadjuvant chemotherapy at the National Cancer Center in Goyang, Korea from April 2016 to October 2019. We retrospectively collected the clinicopathologic information and AR expression results and analyzed the data according to cancer stage, hormonal receptor (HR) status, human epidermal growth factor receptor 2 (HER2) status, tumor subtype, and pCR. RESULTS: Among the 624 breast cancer patients, 529 (84.8%) were AR-positive (AR+) patients and 95 (15.2%) were AR-negative (AR-) patients. AR+ patients showed more estrogen receptor (ER) positivity, progesterone receptor (PR) positivity, HER2-positivity, and HR-positive and HER2-negative (HR+/HER2-) subtype. The rate of pCR was 31.4% (196/624). AR- patients had a significantly higher rate of pCR than AR+ patients (AR- 43.2% vs. AR+ 29.3%, p=0.007). The tumor factors associated with pCR were early stage, histologic grade 3, ER-negative, PR-negative, AR-negative, HER2-positive, and high Ki-67 values. In univariable analysis, AR+ significantly decreased the state of pCR (odds ratio, 0.546; 95% confidence interval, 0.349 to 0.853; p=0.008). According to tumor subtype, AR- tumor showed higher pCR rate in HR+/HER2- subtype (AR- 28.6% vs. AR+ 7.3%, p=0.022). CONCLUSION: AR expression is predominant in the HR+/HER2- subtype. AR- is significantly associated with the pCR rate in breast cancer patients, especially within HR+/HER2- subtype. When determining neoadjuvant chemotherapy for the HR+/HER2- subtype, AR expression can be considered as a pCR predictive marker.

MicroRNA-145 Impairs Classical Non-Homologous End-Joining in Response to Ionizing Radiation-Induced DNA Double-Strand Breaks via Targeting DNA-PKcs.

DNA double-strand breaks (DSBs) are one of the most lethal types of DNA damage due to the fact that unrepaired or mis-repaired DSBs lead to genomic instability or chromosomal aberrations, thereby causing cell death or tumorigenesis. The classical non-homologous end-joining pathway (c-NHEJ) is the major repair mechanism for rejoining DSBs, and the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) is a critical factor in this pathway; however, regulation of DNA-PKcs expression remains unknown. In this study, we demonstrate that miR-145 directly suppresses DNA-PKcs by binding to the 3'-UTR and inhibiting translation, thereby causing an accumulation of DNA damage, impairing c-NHEJ, and rendering cells hypersensitive to ionizing radiation (IR). Of note, miR-145-mediated suppression of DNA damage repair and enhanced IR sensitivity were both reversed by either inhibiting miR-145 or overexpressing DNA-PKcs. In addition, we show that the levels of Akt1 phosphorylation in cancer cells are correlated with miR-145 suppression and DNA-PKcs upregulation. Furthermore, the overexpression of miR-145 in Akt1-suppressed cells inhibited c-NHEJ by downregulating DNA-PKcs. These results reveal a novel miRNA-mediated regulation of DNA repair and identify miR-145 as an important regulator of c-NHEJ.

Admixture of divergent genomes facilitates hybridization across species in the family Brassicaceae.

Hybridization and polyploidization are pivotal to plant evolution. Genetic crosses between distantly related species are rare in nature due to reproductive barriers but how such hurdles can be overcome is largely unknown. Here we report the hybrid genome structure of xBrassicoraphanus, a synthetic allotetraploid of Brassica rapa and Raphanus sativus. We performed cytogenetic analysis and de novo genome assembly to examine chromosome behaviors and genome integrity in the hybrid. Transcriptome analysis was conducted to investigate expression of duplicated genes in conjunction with epigenome analysis to address whether genome admixture entails epigenetic reconfiguration. Allotetraploid xBrassicoraphanus retains both parental chromosomes without genome rearrangement. Meiotic synapsis formation and chromosome exchange are avoided between nonhomologous progenitor chromosomes. Reconfiguration of transcription network occurs, and less divergent cis-elements of duplicated genes are associated with convergent expression. Genome-wide DNA methylation asymmetry between progenitors is largely maintained but, notably, B. rapa-originated transposable elements are transcriptionally silenced in xBrassicoraphanus through gain of DNA methylation. Our results demonstrate that hybrid genome stabilization and transcription compatibility necessitate epigenome landscape adjustment and rewiring of cis-trans interactions. Overall, this study suggests that a certain extent of genome divergence facilitates hybridization across species, which may explain the great diversification and expansion of angiosperms during evolution.

Subgenome Discrimination in Brassica and Raphanus Allopolyploids Using Microsatellites.

Intergeneric crosses between Brassica species and Raphanus sativus have produced crops with prominent shoot and root systems of Brassica and R. sativus, respectively. It is necessary to discriminate donor genomes when studying cytogenetic stability in distant crosses to identify homologous chromosome pairing, and microsatellite repeats have been used to discriminate subgenomes in allopolyploids. To identify genome-specific microsatellites, we explored the microsatellite content in three Brassica species (B. rapa, AA, B. oleracea, CC, and B. nigra, BB) and R. sativus (RR) genomes, and validated their genome specificity by fluorescence in situ hybridization. We identified three microsatellites showing A, C, and B/R genome specificity. ACBR_msat14 and ACBR_msat20 were detected in the A and C chromosomes, respectively, and ACBR_msat01 was detected in B and R genomes. However, we did not find a microsatellite that discriminated the B and R genomes. The localization of ACBR_msat20 in the 45S rDNA array in ×Brassicoraphanus 977 corroborated the association of the 45S rDNA array with genome rearrangement. Along with the rDNA and telomeric repeat probes, these microsatellites enabled the easy identification of homologous chromosomes. These data demonstrate the utility of microsatellites as probes in identifying subgenomes within closely related Brassica and Raphanus species for the analysis of genetic stability of new synthetic polyploids of these genomes.

Analysis of the tumor characteristics in young age breast cancer patients using collaborative stage data of the Korea Central Cancer Registry.

PURPOSE: This study aimed to evaluate tumor characteristics in young age (20-39 years old) breast cancer (YABC) patients in Korea. MATERIALS AND METHODS: We identified 10,897 breast cancer patients from 2010 to 2015. The data were collected through 10% systematic sampling of the Korea National Cancer Incidence Database (KNCI DB). Tumor size, lymph node status, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status were collected according to the Collaborative Stage version 2 (CSv2) Data Collection System. RESULTS: Of the 10,897 patients, 1245 (11.4%) were YABC patients. They were found to have larger tumors (T2: 41.6% in 20-39 age group vs 36.4% in 40-49 age group vs 36.5% in 50-59 age group vs 38.4% in ≥ 60 age group; T3: 10.1% vs 7.3% vs 6.5% vs 6.2%, P < .0001), greater rates of lymph node involvement (41.2% vs 32.7% vs 35.7% vs 32.5%, P < .0001), higher tumor grade (High grade: 26.8% vs 19.4% vs 23.5% vs 22.1%, P < .0001), and a larger proportion of triple-negative subtype (18.2% vs 11.0% vs 12.2% vs 13.5%, P < .0001). Compared to the 40-49 age group, breast cancer-related survival (BCRS) rates were worse (91.74% vs 95.04%, P < .0001), and the characteristics of YABC patients were associated with higher risk of death from breast cancer. CONCLUSION: YABC patients have more aggressive tumor characteristics and worse survival rates. Therefore, we need to identify high-risk groups among YABC patients and support active surveillance in them. These findings from a national cohort provide important information for establishing a national cancer care strategy to manage YABC patients.

Reduced fertility caused by meiotic defects and micronuclei formation during microsporogenesis in xBrassicoraphanus.

BACKGROUND: Hybridization and polyploidization events are important driving forces in plant evolution. Allopolyploids formed between different species can be naturally or artificially created but often suffer from genetic instability and infertility in successive generations. xBrassicoraphanus is an intergeneric allopolyploid obtained from a cross between Brassica rapa and Raphanus sativus, providing a useful resource for genetic and genomic study in hybrid species. OBJECTIVE: The current study aims to understand the cause of hybrid sterility and pollen abnormality in different lines of synthetic xBrassicoraphanus from the cytogenetic perspective. METHODS: Alexander staining was used to assess the pollen viability. Cytogenetic analysis was employed to monitor meiotic chromosome behaviors in pollen mother cells (PMCs). Origins of parental chromosomes in xBrassicoraphanus meiocytes were determined by genome in situ hybridization analysis. RESULTS: The xBrassicoraphanus lines BB#4 and BB#6 showed high rates of seed abortion and pollen deformation. Abnormal chromosome behaviors were observed in their PMCs, frequently forming univalents and inter-chromosomal bridges during meiosis. A positive correlation also exists between meiotic defects and the formation of micronuclei, which is conceivably responsible for unbalanced gamete production and pollen sterility. CONCLUSION: These results suggest that unequal segregation of meiotic chromosomes, due in part to non-homologous interactions, is responsible for micronuclei and unbalanced gamete formation, eventually leading to pollen degeneration and inferior fertility in unstable xBrassicoraphanus lines.

Therapeutic efficacy of modified anti-miR21 in metastatic prostate cancer.

Despite improved therapeutic efficacy of the locked nucleic acid (LNA)- and peptide nucleic acid (PNA)-modified antisense microRNAs (anti-miRs), their wider application in clinical practice is still not thoroughly investigated. This study aimed to investigate the stability and therapeutic efficacy of the modified LNA- and PNA-type anti-miRs in a murine prostate cancer model under various treatment conditions. After verifying the anti-cancer potential of anti-miR21 by targeting tumor suppressor PTEN, the potential of the modified LNA- and PNA-type anti-miR21s was compared in vitro and in vivo. We found that PNA-type anti-miR21 showed better stability and therapeutic efficacy in the xenografted mouse tumor model than the LNA-type anti-miR21. Furthermore, PNA-type anti-miR21 treatment showed reduced tumor metastasis. This study may serve as a ground for exploring diverse choices in therapeutic oligonucleotide modification techniques to improve cancer treatment.

Meiotic Chromosome Stability and Suppression of Crossover Between Non-homologous Chromosomes in xBrassicoraphanus, an Intergeneric Allotetraploid Derived From a Cross Between Brassica rapa and Raphanus sativus.

Hybridization and polyploidization are major driving forces in plant evolution. Allopolyploids can be occasionally formed from a cross between distantly related species but often suffer from chromosome instability and infertility. xBrassicoraphanus is an intergeneric allotetraploid (AARR; 2n = 38) derived from a cross between Brassica rapa (AA; 2n = 20) and Raphanus sativus (RR; 2n = 18). xBrassicoraphanus is fertile and genetically stable, while retaining complete sets of both B. rapa and R. sativus chromosomes. Precise control of meiotic recombination is essential for the production of balanced gametes, and crossovers (COs) must occur exclusively between homologous chromosomes. Many interspecific hybrids have problems with meiotic division at early generations, in which interactions between non-homologous chromosomes often bring about aneuploidy and unbalanced gamete formation. We analyzed meiotic chromosome behaviors in pollen mother cells (PMCs) of allotetraploid and allodiploid F1 individuals of newly synthesized xBrassicoraphanus. Allotetraploid xBrassicoraphanus PMCs showed a normal diploid-like meiotic behavior. By contrast, allodiploid xBrassicoraphanus PMCs displayed abnormal segregation of chromosomes mainly due to the absence of homologous pairs. Notably, during early stages of meiosis I many of allodiploid xBrassicoraphanus chromosomes behave independently with few interactions between B. rapa and R. sativus chromosomes, forming many univalent chromosomes before segregation. Chromosomes were randomly assorted at later stages of meiosis, and tetrads with unequal numbers of chromosomes were formed at completion of meiosis. Immunolocalization of HEI10 protein mediating meiotic recombination revealed that COs were more frequent in synthetic allotetraploid xBrassicoraphanus than in allodiploid, but less than in the stabilized line. These findings suggest that structural dissimilarity between B. rapa and R. sativus chromosomes prevents non-homologous interactions between the parental chromosomes in allotetraploid xBrassicoraphanus, allowing normal diploid-like meiosis when homologous pairing partners are present. This study also suggests that CO suppression between non-homologous chromosomes is required for correct meiotic progression in newly synthesized allopolyploids, which is important for the formation of viable gametes and reproductive success in the hybrid progeny.

Effect of Age on Laparoscopic Surgery and Postoperative Chemotherapy in Elderly Patients With Colorectal Cancer.

PURPOSE: We aimed to evaluate the postoperative complications of laparoscopic colorectal cancer (CRC) surgery and the adverse events of postoperative chemotherapy in elderly patients compared to younger patients and to identify the factors influencing the termination of postoperative chemotherapy. METHODS: Between June 2015 and May 2018, 188 patients with CRC underwent laparoscopic surgery with curative intent. Patients aged ≥ 70 were defined as elderly. Postoperative complications and adverse events of chemotherapy were assessed by using the Clavien-Dindo classification and the Common Terminology Criteria for Adverse Events, respectively. The clinicopathological factors were analyzed retrospectively. RESULTS: Seventy-eight patients were considered elderly with a mean age of 77.5 ± 5.5 years. Overall postoperative complications occurred in 68 patients (36.2%). Age and primary tumor location were independent predictors of overall postoperative complications. Smoking history was the only independent predictor of major postoperative complications. Of 113 patients who were recommended postoperative chemotherapy, 90 patients (79.6%) received postoperative chemotherapy. Overall adverse events occurred in 40 patients (44.4%). The American Society of Anesthesiologists physical status classification and chemotherapy regimen were significantly associated with overall adverse events. The chemotherapy regimen was the only factor significantly associated with severe adverse events. Of 90 patients, postoperative chemotherapy could not be completed in 11 (12.2%). Age was the only factor significantly associated with stopping postoperative chemotherapy (P = 0.003). CONCLUSION: This study shows that laparoscopic CRC surgery and postoperative chemotherapy were feasible in elderly patients. Further efforts are needed to ensure that elderly patients have the opportunity to make informed decisions regarding postoperative chemotherapy.

Effect of multi-ethnicity and ancestry on prevalence of allergic disease.

BACKGROUND/PURPOSE: Differences exist among racial and ethnic groups in the prevalence and severity of allergic diseases. However, influence of population admixing on allergic disease has not been studied. We examined the effect of population admixing on the occurrence of allergic disease. METHODS: We reviewed the data of 68,043 adolescents who participated in the 11th Korea Youth Risk Behavior Web-based Survey, which provides a sample that is representative of the entire Korean middle school and high school student population. Multi-ethnic status was determined by using parental country of birth and prevalence of asthma, allergic rhinitis (AR), and atopic dermatitis (AD) was determined by questionnaire. RESULTS: Multi-ethnic adolescents accounted for approximately 0.9% of the total adolescents. Prevalence of asthma was significantly higher in multi-ethnic group than non multi-ethnic group while that of AR and AD was significantly higher in non multi-ethnic group than multi-ethnic group. Parental region of country at birth showed a significant difference in prevalence of allergic disease. Univariate analysis found that urbanity, perceived economic status (PES), parental region of country at birth, and environmental tobacco smoke (ETS) showed a significant odds ratio (OR) in asthma, AR, and AD. Body mass index (BMI) showed a significant OR in asthma and AD. After adjusting for urbanity, PES, BMI and ETS, multiethnicity showed significantly lower OR in AR and AD. CONCLUSION: Population admixing appears to have significant effect on the prevalence of allergic disease. Further study will be needed to clarify the effect of population admixing on prevalence of allergic disease.

FHL1-mutated reducing body myopathy.

Here, we report about reducing body myopathy, associated with a mutation in the four and a half LIM domain 1 gene (FHL1), identified in a 40-year-old woman who was suffering from subtle muscle weakness since the age of six and a limping gait since the age of 22 years. In addition to her elevated muscle enzyme level and magnetic resonance imaging, myopathy was highly suspected considering progression of symptoms. Nerve conduction studies and electromyogram suggested myopathy. The muscle biopsy revealed severe dystrophic features with many reducing bodies on hematoxylin and eosin, nicotinomide adenine dinucleotide dehydrogenase-tetrazolium reductase (NADH-TR), and modified Gomori stains and ubiquitin immunohistochemistry. Whole-exome sequencing revealed Xq26.3 encoding FHL1 missense mutations (NM_001159704) in exon 4: p.C150R, c.T448C. FHL1-mutated "reducing body myopathy" is worth reporting based on its rarity and unique clinicopathologic features including ultrastructure. The confirmative diagnosis is still very difficult before gene analysis because clinical and pathological features of this disease overlap with other myofibrillar myopathies. We stress the importance of genotype-phenotype correlation to obtain a precise diagnosis.

Rapidly Progressive Small Bowel Necrosis in a Previously Healthy Child without Proven Mechanical Obstruction.

Bowel ischemia is a life-threatening surgical emergency. We report a case of rapidly progressive bowel necrosis in a previously healthy child without proven mechanical small bowel obstruction. The definite diagnosis was established at the time of an exploratory operation. Of note, imaging studies and even a laparotomy did not reveal any evidence of acute appendicitis or mechanical obstruction such as intussusception or Meckel's diverticulum. During hospitalization, since we could not rule out surgical abdomen after inconclusive image findings, we closely followed the patient and repeated physical examinations carefully. Eventually surgical exploration was performed based on changes in clinical condition, which proved to be the right decision for the patient. We propose that in children with suspected strangulation of small bowel obstruction, especially when imaging findings do not provide a conclusive diagnosis, the timely exploratory surgical approach ought to be chosen based on carefully observed clinical findings and other evaluations.

Roles of Bcl-2 and caspase-9 and -3 in CD30-induced human eosinophil apoptosis.

BACKGROUND/PURPOSE: Activation of cell surface CD30 by immobilized anti-CD30 monoclonal antibodies (mAb) induces strong apoptosis in human eosinophils. This anti-CD30 mAb-induced eosinophil apoptosis is inhibited by the addition of inhibitors of p38, ERK1/2 mitogen-activated protein kinases, and phosphatidylinositol 3-kinase. However, there is little data investigating the role of Bcl-2 and caspases in eosinophil apoptosis induced by anti-CD30 mAb. We sought to determine whether anti-CD30 mAb induces human eosinophil apoptosis via Bcl-2 and caspase pathways. METHODS: Peripheral blood was drawn from 37 healthy volunteers. The CD30 expression on eosinophils was measured at various time points. Eosinophils were then cultured in plates precoated with anti-CD30 mAb (clone Ber-H8), isotype control immunoglobulin G1, interleukin (IL)-5, or dexamethasone. Western blot analysis was performed to determine the expression of Bcl-2, procaspase-8, -9, and -3, and caspase-8, -9, and -3 after cross-linking of CD30. Human eosinophils were also cultured in plates precoated with anti-CD30 mAb (clone Ber-H8) in the presence or absence of caspase-9 or -3 inhibitors. Eosinophil apoptosis was assessed using flow cytometry. RESULTS: The addition of anti-CD30 mAb significantly increased eosinophil apoptosis compared with controls. In western blot analysis, the addition of anti-CD30 mAb significantly decreased the expression of Bcl-2 and procaspase-9 and -3 and increased the expression of caspase-9 and -3. The addition of caspase-9 or -3 inhibitors decreased anti-CD30 mAb-induced human eosinophil apoptosis. Procaspase-8 or caspase-8 expression was not changed in response to various stimuli. CONCLUSION: Anti-CD30 mAb-induced human eosinophil apoptosis is likely to be mediated through Bcl-2 and caspase-9 and -3.

miR146a-mediated targeting of FANCM during inflammation compromises genome integrity.

Inflammation is a potent inducer of tumorigenesis. Increased DNA damage or loss of genome integrity is thought to be one of the mechanisms linking inflammation and cancer development. It has been suggested that NF-κB-induced microRNA-146 (miR146a) may be a mediator of the inflammatory response. Based on our initial observation that miR146a overexpression strongly increases DNA damage, we investigated its potential role as a modulator of DNA repair. Here, we demonstrate that FANCM, a component in the Fanconi Anemia pathway, is a novel target of miR146a. miR146a suppressed FANCM expression by directly binding to the 3' untranslated region of the gene. miR146a-induced downregulation of FANCM was associated with inhibition of FANCD2 monoubiquitination, reduced DNA homologous recombination repair and checkpoint response, failed recovery from replication stress, and increased cellular sensitivity to cisplatin. These phenotypes were recapitulated when miR146a expression was induced by overexpressing the NF-κB subunit p65/RelA or Helicobacter pylori infection in a human gastric cell line; the phenotypes were effectively reversed with an anti-miR146a antagomir. These results suggest that undesired inflammation events caused by a pathogen or over-induction of miR146a can impair genome integrity via suppression of FANCM.

Infliximab ameliorates AD-associated object recognition memory impairment.

Dysfunctions in the perirhinal cortex (PRh) are associated with visual recognition memory deficit, which is frequently detected in the early stage of Alzheimer's disease. Muscarinic acetylcholine receptor-dependent long-term depression (mAChR-LTD) of synaptic transmission is known as a key pathway in eliciting this type of memory, and Tg2576 mice expressing enhanced levels of Aß oligomers are found to have impaired mAChR-LTD in this brain area at as early as 3 months of age. We found that the administration of Aß oligomers in young normal mice also induced visual recognition memory impairment and perturbed mAChR-LTD in mouse PRh slices. In addition, when mice were treated with infliximab, a monoclonal antibody against TNF-α, visual recognition memory impaired by pre-administered Aß oligomers dramatically improved and the detrimental Aß effect on mAChR-LTD was annulled. Taken together, these findings suggest that Aß-induced inflammation is mediated through TNF-α signaling cascades, disturbing synaptic transmission in the PRh, and leading to visual recognition memory deficits.

Pentraxin 3 as a clinical marker in children with lower respiratory tract infection.

BACKGROUND: Pentraxin 3 (PTX-3) is an acute-phase protein that increases in the plasma during inflammation. OBJECTIVE: We aimed to evaluate the usefulness of PTX-3 as a clinical marker in children with lower respiratory tract infection (LRTI) and examine the correlation of PTX-3 with other biomarkers such as C-reactive protein (CRP) and procalcitonin (PCT). METHODS: We enrolled 117 consecutive patients admitted to Seoul St. Mary's Hospital with LRTI using the WHO criteria. We recorded data on fever duration and peak temperature before admission, duration of fever after admission, respiratory rate, heart rate, oxygen saturation upon admission, duration of oxygen supplementation, and duration of hospital stay. Upon admission, white blood cell (WBC) count, erythrocyte sedimentation rate, CRP level were measured. Multiplex respiratory virus polymerase chain reaction was performed using nasal swabs. PTX-3, PCT, and various cytokines were measured after the study had been completed. RESULTS: We found that there was no significant difference in the level of PTX-3 according to the type of viral infection. PTX-3 levels showed a significant correlation with PCT levels, but not with levels of CRP. The level of PTX-3 showed a significant correlation with peak temperature and duration of fever before admission as well as interleukin (IL)-6 levels. PCT levels showed a significant correlation with IL-6 and granulocyte-colony stimulating factor levels, peak temperature, and duration of fever before admission, and duration of hospital stay. CRP levels showed a significant correlation with duration of fever before admission, total WBC count, and neutrophil count. PCT levels significantly predicted a hospital stay of 7 days or more. PTX-3, PCT, and CRP levels showed no correlation with any other clinical features. CONCLUSION: PTX-3 reflected disease severity but failed to predict length of hospital stay. Further studies evaluating the use of PTX-3 as a biomarker in mild LRTI would be useful.

Examining impacts of allergic diseases on psychological problems and tobacco use in Korean adolescents: the 2008-2011 Korean National Health and Nutrition Examination Survey.

PURPOSE: Asthma during adolescence can induce social, psychological, and behavioral problems. We examined the impact of asthma and other allergic diseases on psychological symptoms and health risk behaviors among South Korean adolescents. METHODS: In this population-based cross-sectional study, 3192 adolescents (10-18 years of age) participating in the 2008-2011 Korean National Health and Nutrition Examination Survey were enrolled. Psychological problems associated with clinically diagnosed asthma, allergic rhinitis, and atopic dermatitis were assessed using questionnaires and surveys. Data was analyzed using logistic regression to determine the association of depression with allergic disease while controlling for age, sex, body mass index, smoking experience, and alcohol use. RESULTS: Asthma and atopic dermatitis were associated with a higher prevalence of depression (17.2% and 13%, respectively). After adjusting for the covariates, asthma patients were approximately two times as likely to have depression as non-allergic participants (odds ratio, 1.81; 95% confidence interval, 1.22-2.68). Psychosocial stress significantly increased in the following order: no allergy, any allergy without asthma, asthma only, and asthma with any allergy (p for linear trend = 0.01). The asthma without other allergies group showed the highest prevalence of cigarette smoking (p = 0.007). CONCLUSIONS: In this study, asthma with or without other allergies was significantly related to increases in depression, psychosocial stress, and smoking experience. Thus, care should be taken to adjust treatment to account for the psychological symptoms and health risk behaviors common among asthmatic adolescents.