Accurate detection of homologous recombination deficiency (HRD) in cancer patients is paramount in clinical applications, as HRD confers sensitivity to poly(ADP-ribose) polymerase (PARP) inhibitors. With the advances in genome sequencing technology, mutational profiling on a genome-wide scale has become readily accessible, and our knowledge of the genomic consequences of HRD has been greatly expanded and refined. Here, we review the recent advances in HRD detection methods. We examine the copy number and structural alterations that often accompany the genome instability that results from HRD, describe the advantages of mutational signature-based methods that do not rely on specific gene mutations, and review some of the existing algorithms used for HRD detection. We also discuss the choice of sequencing platforms (panel, exome, or whole-genome) and catalog the HRD detection assays used in key PARP inhibitor trials.

Chemotherapy-induced alopecia and hair loss can be stressful in patients with cancer. The hair grows back, but sometimes the hair tends to stay thin. Therefore, understanding mechanisms regulating hair regeneration may improve the management of chemotherapy-induced alopecia. Previous studies have revealed that chemotherapeutic agents induce a hair follicle vascular injury. As hair growth is associated with micro-vessel regeneration, we postulated that the stimulation of angiogenesis might enhance hair regeneration. In particular, mice treated with 5-fluorouracil (5-FU) showed delayed anagen initiation and reduced capillary density when compared with untreated controls, suggesting that the retardation of anagen initiation by 5-FU treatment may be attributed to the loss of perifollicular micro-vessels. We investigated whether the ETS transcription factor ETV2 (aka ER71), critical for vascular development and regeneration, can promote angiogenesis and hair regrowth in a 5-FU-induced alopecia mouse model. Tie2-Cre; Etv2 conditional knockout (CKO) mice, which lack Etv2 in endothelial cells, presented similar hair regrowth rates as the control mice after depilation. Following 5-FU treatment, Tie2-Cre; Etv2 CKO mice revealed a significant reduction in capillary density, anagen induction, and hair restoration when compared with controls. Mice receiving lentiviral Etv2 injection after 5-FU treatment showed significantly improved anagen induction and hair regrowth. Two-photon laser scanning microscopy revealed that enforced Etv2 expression restored normal vessel morphology after 5-FU mediated vessel injury. Our data suggest that vessel regeneration strategies may improve hair regrowth after chemotherapeutic treatment.

Chemotherapy-induced alopecia and hair loss can be stressful in patients with cancer. The hair grows back, but sometimes the hair tends to stay thin. Therefore, understanding mechanisms regulating hair regeneration may improve the management of chemotherapy-induced alopecia. Previous studies have revealed that chemotherapeutic agents induce a hair follicle vascular injury. As hair growth is associated with micro-vessel regeneration, we postulated that the stimulation of angiogenesis might enhance hair regeneration. In particular, mice treated with 5-fluorouracil (5-FU) showed delayed anagen initiation and reduced capillary density when compared with untreated controls, suggesting that the retardation of anagen initiation by 5-FU treatment may be attributed to the loss of perifollicular micro-vessels. We investigated whether the ETS transcription factor ETV2 (aka ER71), critical for vascular development and regeneration, can promote angiogenesis and hair regrowth in a 5-FU-induced alopecia mouse model. Tie2-Cre; Etv2 conditional knockout (CKO) mice, which lack Etv2 in endothelial cells, presented similar hair regrowth rates as the control mice after depilation. Following 5-FU treatment, Tie2-Cre; Etv2 CKO mice revealed a significant reduction in capillary density, anagen induction, and hair restoration when compared with controls. Mice receiving lentiviral Etv2 injection after 5-FU treatment showed significantly improved anagen induction and hair regrowth. Two-photon laser scanning microscopy revealed that enforced Etv2 expression restored normal vessel morphology after 5-FU mediated vessel injury. Our data suggest that vessel regeneration strategies may improve hair regrowth after chemotherapeutic treatment.

INTRODUCTION: Several studies on the effectiveness of exercise in improving sleep quality in the elderly have been done but have conficting results. This meta-analysis aimed to determine the effect of low- to moderate-intensity aerobic exercise in improving sleep quality among the elderly. METHODS: EBSCO, ClinicalKey, PubMed, Wiley Online Library, and Cochrane Library were searched for articles using the terms “exercise AND sleep quality AND elderly”. The risk of bias assessment was done using the Cochrane Collaboration tool and encoded using RevMan 5.4. Data on outcome measures were subjected to meta-analysis using inverse variance methods. RESULTS: Seven articles with a total of 225 participants were included. There was a statistically signifcant improvement in sleep quality with low to moderate intensity aerobic exercise (MD = -3.87 points; 95% CI -5.56, -2.19 points; p < 0.001). There was a statistically signifcant decrease in total sleep time after intervention (MD = -8.86; 95% CI -16.31, -1.41 points; p = 0.02). There was no improvement in sleep effciency. CONCLUSION Low and moderate intensity exercise improves sleep quality in the elderly and may be used as a non-pharmacologic intervention to enhance sleep quality.

BACKGROUND: Herpes zoster (HZ) is caused by reactivation of latent varicella-zoster virus (VZV) infection. HZ-associated aseptic meningitis, a rare complication of HZ, can require hospitalization and a long treatment period. OBJECTIVE: A retrospective study was performed to identify potential factors associated with HZ-associated aseptic meningitis development. METHODS: We included all outpatients and patients admitted in the neurology and dermatology departments of a single tertiary center, who were diagnosed with HZ for two years. Among 818 patients, 578 patients were eligible for analysis. RESULTS: The demographics and potential risk factors were compared between the uncomplicated HZ group (n=554) and aseptic meningitis group (n=24). Among the potential factors, the dermatological distribution of skin rash and gender showed statistically significantly different between the two groups. Patients with craniocervical distribution of HZ accounted for 87.5% (n=21) of the aseptic meningitis group and 54.3% (n=301) of the uncomplicated HZ group (p=0.043). The aseptic meningitis group had more men (66.7%, n=16) than the uncomplicated HZ group (42.8%, n=237, p=0.033). Patients with craniocervical distribution had an odds ratio (OR) of 5.884 (p=0.001) for developing aseptic meningitis when compared with the other dermatome involvements. Additional logistic regression analysis resulted in a fading between gender difference (p=0.050) and craniocervical involvement having an OR of 5.667 for aseptic meningitis (p=0.006). CONCLUSION: In HZ patients, skin rash with craniocervical distribution and male gender were associated with a higher risk of aseptic meningitis.
Demography ; Dermatology ; Exanthema ; Herpes Zoster* ; Herpesvirus 3, Human ; Hospitalization ; Humans ; Logistic Models ; Male ; Meningitis ; Meningitis, Aseptic* ; Neurology ; Odds Ratio ; Outpatients ; Retrospective Studies ; Risk Factors*

BACKGROUND AND PURPOSE: Cholinesterase inhibitors (ChEIs) are effective in Alzheimer's disease (AD) treatment. The aim of this study is 1) to find neuropsychological factors that affect the functional response to ChEI therapy and 2) to determine whether regional cerebral blood flow (rCBF) pretreatment predicts a cognitive change in response to ChEI. METHODS: We prospectively recruited 32 patients diagnosed with probable AD and treated them with donepezil, a ChEI, over one year. The patients were divided into stable (s-AD) and declined (d-AD) AD groups, based on changes in Korean version of Mini-Mental State Examination (K-MMSE) scores. Patients were assessed using the Alzheimer's Disease Co-operative Study-Activities of Daily Living (ADCS-ADL) and Seoul Neuropsychologic Screening Battery, as well as brain single photon emission computerized tomography (SPECT) at baseline and last medical evaluations. The predictors of therapeutic responses were analyzed using general linear models. RESULTS: Based on their cognitive function changes, AD patients were classified into two groups: s-AD (n=14, annual change in K-MMSE score <0.9), or d-AD (n=18, annual change in K-MMSE score > or =0.9). The s-AD at baseline showed significantly better ADCS-ADL function (p=0.04) and had a tendency to preserve frontal function compared to the d-AD group. Global Statistical Parametric Mapping analysis revealed no significant decrease of rCBF between baseline and follow-up SPECT, in either the s-AD or the d-AD groups. However, on regional perfusion analysis of baseline SPECT, the d-AD group demonstrated perfusion deficits in the supramarginal gyrus, inferior occipital gyrus, and rolandic operculum compared with the s-AD group. CONCLUSIONS: Highly preserved ADCS-ADLs predicted a better improvement in MMSE scores in response to ChEI therapy and a more positive functional response in the group with preserved frontal function. rCBF provided hints to the variable response to donepezil therapy with ChEI treatment.
Alzheimer Disease* ; Brain ; Cholinesterase Inhibitors ; Follow-Up Studies ; Humans ; Linear Models ; Mass Screening ; Neuropsychological Tests* ; Perfusion ; Prospective Studies ; Seoul ; Tomography, Emission-Computed, Single-Photon*

OBJECTIVE: Wine has been the focus in the prevention of epithelial ovarian cancer (EOC) development because resveratrol abundant in wine has anti-carcinogenic properties. However, epidemiologic results have been heterogenous in the chemopreventive effect of wine on the development of EOC. Thus, we performed a meta-analysis for comparing EOC risk between wine and never drinkers using previous related studies. METHODS: After extensive search of the literature between January 1986 and December 2008, we analyzed 10 studies (3 cohort and 7 case control studies) with 135,871 women, who included 65,578 of wine and 70,293 of never drinkers. RESULTS: In all studies, there was no significant difference in EOC risk between wine and never drinkers (odds ratio [OR], 1.13; 95% confidence interval [CI], 0.92 to 1.38; random effects). When we performed re-analysis according to the study design, 3 cohort and 7 case control studies showed that there were also no significant differences in EOC risk between wine and never drinkers, respectively (OR, 1.44 and 1.04; 95% CI, 0.74 and 2.82 and 0.88 to 1.22; random effects). In sub-analyses using 2 case-control studies, EOC risk was not different between former and never drinkers (OR, 1.12; 95% CI, 0.87 to 1.44; fixed effect), and between current and former drinkers (OR, 0.74; 95% CI, 0.41 to 1.34; random effects). CONCLUSION: Although resveratrol, abundantly found in wine, is a promising naturally occurring compound with chemopreventive properties on EOC in preclinical studies, this meta-analysis suggests the epidemiologic evidence shows no association between wine drinking and EOC risk.
Case-Control Studies ; Cohort Studies ; Drinking ; Female ; Humans ; Neoplasms, Glandular and Epithelial ; Ovarian Neoplasms ; Stilbenes ; Wine

BACKGROUND/AIMS: Primary appendiceal adenocarcinoma is a rare neoplasm that constitutes less than 0.5% of all gastrointestinal neoplasm. The aim of this study was to figure out its clinicopathologic characteristics that are not well understood. METHODS: We reviewed the medical records of nineteen patients (9 males and 10 females) with histologically proven appendiceal adenocarcinoma. They had been treated at Asan Medical Center between June 1989 and December 2002. Their median follow-up duration was 72.5 months. RESULTS: Their median age was 56.5 (range, 33~80) years. Thirteen patients had mucinous variants and the other five had adenocarcinoma. Seven patients (36.8%) were diagnosed as acute appendicitis. In fact, none of the patients was diagnosed correctly before surgery. The operative procedure, included right hemicolectomy in 9 patients, appendectomy alone in 2 patients, and debulking of their tumors or a biopsy in 8 patients. The 5-year survival rate was 20.5%. The patients with mucinous type had better prognosis than those with the non-mucinous type (p<0.01). In the patients with mucinous type, the survival rate after debulking operation was similar to that after right hemicolectomy. CONCLUSIONS: The most important prognostic factor of primary appendiceal adenocarcinoma was histology. The outcome of debulking operation is being watched compared with that of right hemicolectomy in mucinous variant.
Adenocarcinoma/*diagnosis/mortality/surgery ; Adult ; Aged ; Appendiceal Neoplasms/*diagnosis/mortality/surgery ; English Abstract ; Female ; Humans ; Male ; Middle Aged ; Prognosis ; Survival Rate

BACKGROUND/AIMS: We aimed to verify the prognostic factors of stage II rectal cancer and the effect of radiation therapy on the survival and local recurrence rate. METHODS: This study was undertaken in 202 patients who underwent curative resection of rectal cancer and confirmed to be stage II between July 1989 and December 1996. Univariate and multivariate (Cox's model) analyses of survival were employed to identify prognostic factors. Statistical significance was assigned by p value of <0.05. RESULTS: Overall recurrence occurred in 32 patients. Four patterns of recurrence were observed: hematogenous recurrence in 17 patients, local recurrence in 11, peritoneal seeding in two and simultaneous hematogenous and local recurrence in two cases. Overall 5-year survival rate was 85.6% and 5 year disease free survival rate was 82.8%. There was no significant difference in local recurrence rate and survival according to radiation therapy or location of cancer. In multivariate analysis, the number of harvested lymph node was only a prognostic factor. CONCLUSIONS: The number of harvested lymph nodes has prognostic value in stage II rectal cancer. Postoperative radiation therapy should be considered for stage II rectal cancer with poor prognostic factors although radiation did not decrease local recurrence rate in present study.
Adolescent ; Adult ; Aged ; Child ; English Abstract ; Female ; Humans ; Male ; Middle Aged ; Neoplasm Metastasis ; Neoplasm Recurrence, Local ; Prognosis ; Rectal Neoplasms/pathology/*surgery

Bovine mastitis is an infectious disease with a major economic influence on the dairy industry worldwide. Many factors such as environment, pathogen, and host affect susceptibility or resistance of an individual cow to bovine mastitis. Recently, there has been considerable interest in defining genetic and immunological markers that could be used to select for improved disease resistance. In this study we have analyzed the lymphocyte subpopulations of mastitis-resistant and susceptible cows using monoclonal antibodies specific for bovine leukocyte differentiation antigens and flow cytometry. We have also used a microarray typing technique to define the bovine leukocyte antigen (BoLA) class I and class II haplotypes associated with resistance or susceptibility to bovine mastitis. A striking finding of the present study is that susceptibility to mastitis was associated with major histocompatibility complex (MHC) haplotypes that have only a single set of DQ genes. The study also revealed that susceptible cows had CD4:CD8 ratios of less than one in both their mammary gland secretions and peripheral blood. These results raise the possibility that the number of DQ genes that a cow has and/or a cow's CD4:CD8 ratio could be used as indicators of susceptibility to bovine mastitis.
Alleles ; Animals ; Antigens, Differentiation/immunology ; Cattle ; Cell Count/veterinary ; Female ; Flow Cytometry/veterinary ; Genetic Predisposition to Disease ; Histocompatibility Antigens/genetics/immunology ; Korea ; Leukocytes, Mononuclear/cytology/*immunology/microbiology ; Lymphocyte Subsets/*immunology/microbiology ; Mastitis, Bovine/genetics/*immunology/microbiology ; Oligonucleotide Array Sequence Analysis/veterinary ; Statistics, Nonparametric