The ins and outs of male breast and anterior chest wall lesions from childhood to adulthood.

Physiological and pathological processes arising from the breast and anterior chest wall may share similar clinical presentations because of the small volume of male breasts. Therefore, imaging is frequently required to localise and characterise the lesion and guide biopsy when radiological findings are equivocal or suspicious. Mammography or digital breast tomosynthesis (DBT) and ultrasound are the mainstays of breast imaging work-up. Other imaging techniques such as computed tomography (CT), magnetic resonance imaging (MRI) and positron-emission tomography (PET) can sometimes augment the investigation and aid treatment planning. This article reviews the key imaging features of a wide spectrum of benign and malignant conditions that involve the male breast and anterior chest wall across various age groups. Familiarisation with the salient radiological findings is essential for reaching an accurate diagnosis and optimising management.

Association of sepsis with risk for osteoporosis: a population-based cohort study.

We conducted a large, retrospective cohort study using data from Taiwan's National Health Insurance Research Database to evaluate whether the risk of developing osteoporosis is associated with sepsis. Our study found that adults younger than 65 years with sepsis had a significantly increased risk of developing osteoporosis. INTRODUCTION: There have been limited studies regarding the osteoporosis risk associated with sepsis. Our purpose is to evaluate whether the risk of developing osteoporosis is associated with sepsis. METHODS: We conducted a large, retrospective cohort study using data from Taiwan's National Health Insurance Research Database. From the insurance claims data, a total of 13,178 patients diagnosed with sepsis from 2000 to 2012 were included in the sepsis cohort, and a propensity score-matched cohort included 13,178 individuals without sepsis. To calculate the incidence of osteoporosis, both groups were followed until 2013. Cox regression analysis was performed to obtain the hazard ratios (HRs) to assess the risk of developing osteoporosis. The Kaplan-Meier method was used to estimate the cumulative incidence of osteoporosis. RESULTS: The overall incidences of osteoporosis (per 1,000 person-years) in the sepsis and non-sepsis groups were 10.2 and 10.7, respectively. The risk of osteoporosis significantly increased in the presence of sepsis (adjusted HR = 1.17, 95% confidence interval (CI) = 1.04-1.31). The risk of osteoporosis in the sepsis group was significantly higher than that in the non-sepsis group for young patients aged 20-49 years and patients aged 50-64 years (adjusted HR = 1.93, 95% CI = 1.08-3.44; adjusted HR = 2.01, 95% CI = 1.52-2.65, respectively). The Kaplan-Meier curves of cumulative probability also showed a significantly increased risk of osteoporosis in patients aged 20-49 years and aged 50-64 years with sepsis compared with non-sepsis (P = 0.025; P < 0.001, respectively). CONCLUSION: Adults younger than 65 years with sepsis had a significantly increased risk of developing osteoporosis.

Indistinguishable heralded single photon generation via relative temporal multiplexing of two sources.

Generating N single photons simultaneously is a formidable challenge due to the lack of deterministic single photon sources. Recent work [New J. Phys. 19, 063013 (2017] has proposed a relative multiplexing scheme that can enhance the N single photons probability with a minimum of active switching resources. We experimentally demonstrate relative temporal multiplexing on two photon sources with a 90% additional enhancement over the standard temporal multiplexing scheme demonstrated previously. 88 ± 11% visibility of Hong-Ou-Mandel quantum interference verifies the indistinguishability of the heralded single photons after the synchronization. This proof-of-principle demonstration points out the potential significance of the relative multiplexing scheme for large-scale photonic quantum information processing.

Long-term cognitive and school outcomes of late-preterm and early-term births: a systematic review.

BACKGROUND: Children born before full term (39-41 weeks' gestation) are at increased risk of adverse cognitive outcomes. Risk quantification is important as late-preterm (LPT; 34-36 weeks) and early-term (ET; 37-38 weeks) births are common. METHOD: This review analyses the effect of LPT and ET births on long-term cognitive and educational outcomes. The primary outcome was general cognitive ability. Secondary outcomes included verbal/non-verbal intelligence quotient, subject-specific school performance and special educational needs. The search strategy included Medline and Embase from January 1975 to June 2013. Eligible studies investigated specified outcomes and included suitable gestational age participants assessed at 2 years and older. Outcome measures and socio-demographic descriptors were extracted, and data meta-analysed where possible. RESULTS: Eight studies compared ET birth with full-term birth. Fourteen studies compared LPT birth with either term birth (>37 weeks, n = 12 studies) or full-term birth (39-41 weeks, n = 2 studies). Substantial between-study heterogeneity existed. LPT and ET children underperformed in most outcomes compared with their term/full-term counterparts, respectively. For example, LPT children had an increased risk of lower general cognitive ability (adjusted risk ratio 1.38 [95% confidence interval 1.06-1.79]), and full-term children performed 5% of a standard deviation higher (z-score 0.05 [0.02, 0.08]) than ET children. Poorer outcomes persist into adulthood; term cohorts performed 5% of a standard deviation higher than LPT cohorts (z-score 0.05 [0.04, 0.07]), and full-term cohorts performed 3% of a standard deviation higher than ET cohorts (z-score 0.03 [0.02, 0.04]). CONCLUSION: This review critically examines the knowledge around long-term cognitive outcomes of LPT and ET births, demonstrating multiple, small, adverse differences between LPT/ET and term/full-term births.

What's in a name? Expiratory tracheal narrowing in adults explained.

Tracheomalacia, tracheobronchomalacia, and excessive dynamic airway collapse are all terms used to describe tracheal narrowing in expiration. The first two describe luminal reduction from cartilage softening and the latter refers to luminal reduction from exaggerated posterior membrane movement. Expiratory tracheal narrowing is a frequent occurrence that can cause symptoms of airway obstruction, such as dyspnoea, wheeze, and exercise intolerance. The accurate diagnosis and quantification of expiratory tracheal narrowing has important aetiological, therapeutic, and prognostic implications. The reference standard for diagnosis has traditionally been bronchoscopy; however, this method has significant limitations. Expiratory tracheal disorders are readily detected by four-dimensional dynamic volume multidetector computed tomography (4D-CT), an emerging, non-invasive method that will potentially enable detection and quantification of these conditions. This review discusses the morphological forms of expiratory tracheal narrowing and demonstrates the utility of 4D-CT in the diagnosis, quantification, and treatment of these important conditions.

Bat coronavirus was detected positive from insectivorous bats in Krau Wildlife Reserve Forest.

Bats are flying mammals with unique immune systems that allow them to hold many pathogens. Hence, they are recognised as the reservoir of many zoonotic pathogens. In this study, we performed molecular detection to detect coronaviruses, paramyxoviruses, pteropine orthoreoviruses and dengue viruses from samples collected from insectivorous bats in Krau Reserve Forest. One faecal sample from Rhinolophus spp. was detected positive for coronavirus. Based on BLASTN, phylogenetic analysis and pairwise alignment-based sequence identity calculation, the detected bat coronavirus is most likely to be a bat betacoronavirus lineage slightly different from coronavirus from China, Philippines, Thailand and Luxembourg. In summary, continuous surveillance of bat virome should be encouraged, as Krau Reserve Forest reported a wide spectrum of biodiversity of insectivorous and fruit bats. Moreover, the usage of primers for the broad detection of viruses should be reconsidered because geographical variations might possibly affect the sensitivity of primers in a molecular approach.

Simple techniques for three-dimensional photography of the nose in nasal deformity.

AIM: To investigate the use of anaglyphs and stereograms for three-dimensional imaging of the external nose. METHOD: Red-cyan anaglyphs and colour stereograms created from stereo photographs of patients with nasal deformity were compared to standard photographs. Assessors rated images on 'life-likeness' of imaging, contour definition and utility for surgical planning. RESULTS: 9 patients were recruited. Stereograms provided significantly improved life-like features and definition of nasal structure, with some benefit for pre-operative planning. Less benefit was found for anaglyph images. Oblique views proved most effective. CONCLUSIONS: Stereograms provide simple, inexpensive three-dimensional images of the nose, with potential uses in operative analysis, medicolegal documentation, teaching and research.

The prevalence of oilseed rape hypersensitivity in a mixed cereal farming population.

BACKGROUND: Oilseed rape production is widespread in cereal growing areas. Many patients attending our clinics for seasonal allergy claim that they are allergic to it. AIM: To determine the prevalence of oilseed rape allergy in our population. POPULATION: General population within a mixed cereal farming area attending a rhinology and allergy clinic in a district general hospital, UK. METHODS & MATERIALS: Retrospective chart analysis. The results of 1475 consecutive patients who underwent skin prick allergy testing over a 2-year period (January 2003-December 2005) and of 640 consecutive patients over a 1-year period (September 2008-September 2009) were analysed and compared. RESULTS: Allergy to house dust mite was found to be most common (n = 526, 25%) followed by grass pollen (n = 519, 24%) and cereals (n = 429, 20%). Oilseed rape hypersensitivity was relatively uncommon, comprising only 2% of the population tested (n = 28). CONCLUSION: Oilseed rape does not cause significant allergy, even in areas of high production. It is likely that those patients exhibiting oilseed rape allergy may in fact be symptomatic due to the effect of other allergens, acting either synergistically with the oilseed rape allergen, or more likely, in spite of it.

A twin study of body mass index and dental caries in childhood.

Sub-optimal nutrition and dental caries are both common with significant short and long-term implications for child health and development. We applied twin statistical methods to explore the relationship between body mass index (BMI) and dental caries. We measured BMI at 18 months and six years of age and cumulative dental caries experience at six years in 344 twin children. Dental caries in primary teeth was categorised into 'any' or 'advanced' and BMI was analysed as both a continuous and categorical variable. Statistical analyses included multiple logistic regression using generalized estimating equations and within/between-pair analyses. There was no association between BMI and 'any' dental caries experience at either time-point, neither overall nor in within/between pair analyses. However, 'advanced' dental caries at six years was associated with a within-pair difference in BMI of -0.55 kg/m2 (95% CI -1.00, -0.11, p = 0.015). A within-pair increase of 1 kg/m2 in BMI was associated with a lower within-pair risk of advanced dental caries (OR 0.68, 95% CI 0.52, 0.90, p = 0.007). These findings reveal a possible causal relationship between lower BMI and dental caries. As dental outcomes were only measured at one time point, the direction of this potentially causal relationship is unclear.

Etiology of Hypomineralized Second Primary Molars: A Prospective Twin Study.

The etiology of hypomineralized second primary molars (HSPM) is unclear, but genetic and environmental factors have been proposed. The aim of this study was to investigate the relative contribution of genes and environment to the etiology of HSPM and to identify potential environmental risk factors in a longitudinal twin cohort. Children from twin pregnancies ( N = 250) were recruited antenatally, and detailed demographic, health, and phenotypic data were collected at recruitment, 24- and 36-wk gestation, birth, and 18 mo of age. 25-Hydroxyvitamin D was quantified for mothers at 28-wk gestation and infants at birth. Dental examinations were conducted on the twins at 6 y of age to determine the presence, severity, and extent of HSPM per standardized criteria. To investigate associations of environmental risk factors with HSPM, multiple logistic regression models were fitted with generalized estimating equations to adjust for twin correlation. Within- and between-pair analyses were performed for unshared continuous variables: birthweight and birth 25-hydroxyvitamin D. Twin-twin concordance for monozygotic (MZ) and dizygotic (DZ) pairs was calculated and compared after adjusting for identified risk factors. A total of 344 twins underwent the 6-y-old dental assessment; HSPM occurred in 68 (19.8%). After adjusting for potential confounders, vitamin D levels at birth, infantile eczema, dizygosity, in vitro fertilization, socioeconomic position, and maternal smoking beyond the first trimester of pregnancy demonstrated the strongest associations with HSPM. Overall concordance for HSPM was 0.47 (95% CI, 0.32 to 0.62) with weak evidence ( P = 0.078) of higher concordance in MZ twins (0.63; 95% CI, 0.38 to 0.89) as compared with DZ twins (0.41; 95% CI, 0.24 to 0.58). After adjusting for known risk factors, there was no evidence ( P = 0.172) for an additive genetic influence. These findings suggest that shared and unshared environmental factors, such as maternal smoking later in pregnancy and infantile eczema, are important in the etiology of HSPM.

Awareness of Colorectal Cancer among the Urban Population in the Klang Valley.

BACKGROUND: Colorectal cancer (CRC) is the second most common cancer in Malaysia. Awareness of risk factors, symptoms and warning signs of CRC will help in early detection. This paper presents the level of CRC awareness among the urban population in Malaysia. METHOD: A cross-sectional study was conducted from November 2015 till December 2016 at three government clinics in the Klang Valley. The validated Bowel Cancer Awareness Measure questionnaire in both English and Malay was used. The mean knowledge scores for the warning signs and risk factors of CRC in different socio-demographic groups were compared using ANOVA in SPSS version 23. Statistical significance was set at p<0.05 and a 95% confidence level. RESULTS: Of the 426 respondents, 29.1% were unable to recall the warning signs and symptoms of CRC. Average recall was less than two warning signs and symptoms (mean 1.62, SD 1.33). The mean total knowledge score for CRC was 9.91 (SD 4.78), with a mean knowledge scores for warning signs and risk factors at 5.27 (SD 2.74) and 4.64 (SD 2.78), respectively. Respondents with a higher level of education were found to have higher level of knowledge regarding the warning signs of CRC. There was a significant positive association between knowledge score for warning signs and level of confidence in detecting warning signs. Regarding the total knowledge score for CRC, 3.3% of respondents scored zero. For warning signs and risk factors, 8.2% and 8.5% of respondents had zero knowledge scores, respectively. CONCLUSIONS: Generally, awareness of CRC is poor among the urban population of Klang Valley. Greater education and more confidence in detecting warning signs are significantly associated with better knowledge of warning signs. CRC awareness programs should be increased to improve awareness.

Measurement of fracture callus material properties via nanoindentation.

In bone fracture healing, the extent to which the injured bone regains stability and strength depends on the mechanical properties of the tissues that are formed during healing. While many techniques have been used to quantify the overall mechanical behavior of fracture calluses, few data exist on the material properties of individual callus tissues. The overall goal of this study was to quantify these material properties. Nanoindentation was performed at multiple locations across thin (200mum), longitudinal sections of rat fracture callus at 35 days post fracture. Following indentation, sections were stained with alizarin red S and alcian blue to obtain semi-quantitative estimates of tissue mineral content and proteoglycan content, respectively. Indentation moduli varied over three orders of magnitude (0.61-1010MPa) throughout the callus. Much of this variation was due to the presence of multiple tissue types: the indentation moduli of granulation tissue, chondroid tissue and woven bone ranged 0.61-1.27MPa (median=0.99MPa), 1.39-4.42MPa (median=2.89MPa) and 26.92-1010.00MPa (median=132.00MPa), respectively. In regions of alizarin red staining, the indentation modulus was correlated (r=0.62, P=0.04) with stain intensity, suggesting a positive correlation between modulus and mineral content in woven bone. In addition, the indentation modulus of woven bone along the periosteal aspect of the cortex increased with distance from the fracture gap (P=0.004). These results demonstrate the usefulness of nanoindentation in characterizing the elastic properties of the heterogeneous mixture of tissues present in bone fracture callus.

Analysis of mutation in human cells by using an Epstein-Barr virus shuttle system.

We developed highly sensitive shuttle vector systems for detection of mutations formed in human cells using autonomously replicating derivatives of Epstein-Barr virus (EBV). EBV vectors carrying the bacterial lacI gene as the target for mutation were established in human cells and later returned to Escherichia coli for rapid detection and analysis of lacI mutations. The majority of the clonal cell lines created by establishment of the lacI-EBV vector show spontaneous LacI- frequencies of less than 10(-5) and are suitable for studies of induced mutation. The ability to isolate clonal lines represents a major advantage of the EBV vectors over transiently replicating shuttle vectors (such as those derived from simian virus 40) for the study of mutation. The DNA sequence changes were determined for 61 lacI mutations induced by exposure of one of the cell lines to N-nitroso-N-methylurea. A total of 33 of 34 lacI nonsense mutations and 26 of 27 missense mutations involve G X C to A X T transitions. These data provide support for the mutational theory of cancer.

Distinguishing second primary tumors from lung metastases in patients with head and neck squamous cell carcinoma.

BACKGROUND: In patients with head and neck squamous cell carcinoma (HNSCC), a squamous cell carcinoma (SCC) in the lung represents either another primary tumor or a metastasis. This distinction greatly influences patient prognosis and could guide treatment strategies, but the nature of a solitary lung nodule is often difficult to discern by use of standard clinical and histologic parameters. Comparison of genetic alterations in the tumors could resolve this dilemma. METHODS: We compared paired tumors from 16 patients with HNSCC and a solitary lung SCC for loss (i.e., deletion) of loci on chromosomal arms 3p and 9p. Losses at these loci occur early during neoplastic transformation of the respiratory tract. DNA from microdissected tumors and normal tissues was subjected to polymerase chain reaction-based microsatellite analysis. An effort was also made to distinguish primary lung cancers from lung metastases on the basis of clinical and histopathologic features. RESULTS: In most cases, comparison of genetic alterations clarified the relationship between the lung tumor and the primary HNSCC. The paired tumors from 10 patients had concordant patterns of loss at all loci suggesting metastatic spread, whereas three paired tumors had discordant patterns of loss at all loci suggesting independent tumor origin. These observations were supported by the clinical and pathologic findings. CONCLUSIONS/IMPLICATIONS: In patients with HNSCC and a solitary SCC in the lung, microsatellite analysis provides a rapid genetic approach for discerning clonal relationships. In such patients, we found that a solitary SCC in the lung more likely represents a metastasis than an independent lung cancer. Microsatellite analysis could potentially be applied to any patient with multiple tumors, where tumor relationships are not clear on clinical, radiographic, or even histopathologic grounds.

Killing and mutation of human lymphoblast cells by aflatoxin B1: evidence for an inducible repair response.

Diploid human lymphoblast cells exhibit apparent saturation of mutation induced by exposure to aflatoxin B1, despite a linear increase in the amount and proportion of the aflatoxin-DNA adducts formed. The saturation is neither a cell cycle phenomenon nor a result of a genetically heterozygous population. Examination of the biphasic nature of aflatoxin-DNA adduct loss in vivo shows initial, rapid removal of all adduct species, followed by a slow loss of the aflatoxin-N7-guanine adduct alone. We hypothesize that these data reveal two modes of adduct loss in these cells. The first is an inducible, error-free system that is short-lived, turning off as adduct levels fall below the induction threshold of some 1000 total adducts/cell. The second loss is slower and results from spontaneous depurination of remaining aflatoxin-N7-guanines. Our data are in agreement with the possibility that apurinic sites thus generated are responsible for the mutation observed. A major paradox arises from the fact that aflatoxin-related premutagenic depurinations are estimated to be only 10% of the number of spontaneous depurinations estimated by others to occur in human cells in a 1-h period.

Active temporal multiplexing of indistinguishable heralded single photons.

It is a fundamental challenge in quantum optics to deterministically generate indistinguishable single photons through non-deterministic nonlinear optical processes, due to the intrinsic coupling of single- and multi-photon-generation probabilities in these processes. Actively multiplexing photons generated in many temporal modes can decouple these probabilities, but key issues are to minimize resource requirements to allow scalability, and to ensure indistinguishability of the generated photons. Here we demonstrate the multiplexing of photons from four temporal modes solely using fibre-integrated optics and off-the-shelf electronic components. We show a 100% enhancement to the single-photon output probability without introducing additional multi-photon noise. Photon indistinguishability is confirmed by a fourfold Hong-Ou-Mandel quantum interference with a 91 ± 16% visibility after subtracting multi-photon noise due to high pump power. Our demonstration paves the way for scalable multiplexing of many non-deterministic photon sources to a single near-deterministic source, which will be of benefit to future quantum photonic technologies.

DNA base sequence changes induced by ultraviolet light mutagenesis of a gene on a chromosome in Chinese hamster ovary cells.

The DNA base sequence changes induced by mutagenesis with ultraviolet light have been determined in a gene on a chromosome of cultured Chinese hamster ovary (CHO) cells. The gene was the Escherichia coli gpt gene, of which a single copy was stably incorporated and expressed in the CHO cell genome. The cells were irradiated with ultraviolet light and gpt- colonies were selected by resistance to 6-thioguanine. The gpt gene was amplified from chromosomal DNA by use of the polymerase chain reaction (PCR), and the amplified DNA sequenced directly by the dideoxy method. Of the 58 sequenced mutants of independent origin 53 were base change mutations. Forty-one base substitutions were single base changes, ten had two adjacent (or tandem) base changes, and one had two base changes separated by a single base-pair. Only one mutant had a multiple base change mutation with two or more well separated base changes. In contrast much higher levels of such mutations were reported in ultraviolet mutagenesis of genes on a shuttle vector in primate cells. Two deletions of a single base-pair were observed and three deletions ranging from 6 to 37 base-pairs. The mutation spectrum in the gpt gene had similarities to the ultraviolet mutation spectra for several genes in prokaryotes, which suggests similarities in mutational mechanisms in prokaryotes and eukaryotes.

Comparison of ultraviolet irradiation-induced mutagenesis of the lacI gene in Escherichia coli and in human 293 cells.

We report the sequence changes in the Escherichia coli lacI gene in 133 mutants detected after passage of an ultraviolet-irradiated shuttle vector human 293 cells. The results are compared with our previous studies of the lacI gene after ultraviolet light treatment in E. coli. In human cells, base substitutions predominate, and frameshifts are found much less frequently than in bacteria. The most frequent base change is the G.C to A.T transition. Overall, 110 to 112 transitions were G.C to A.T. Some of the hotspots seen in lacI in bacteria are prominent also in human 293 cells, suggesting that the same lesions are targeting mutations in both systems. Transitions are found almost exclusively at sequences at which pyrimidine-pyrimidine photoproducts can form. The data are consistent with the notion that a significant fraction of ultraviolet irradiation-induced mutagenesis in mammalian systems occurs by adding an A across from a photolesion. Double mutations are significantly more frequent in human cells than in bacteria. Reasons for this difference are discussed.

Second esophageal tumors in patients with head and neck squamous cell carcinoma: an assessment of clonal relationships.

Patients with squamous cell carcinoma of the head and neck (HNSCC) often develop second carcinomas elsewhere in the upper aerodigestive tract. Some of these paired tumors share a common origin, reflecting the ability of a single progenitor cell to replicate, expand, and populate contiguous regions of the upper aerodigestive tract-a process referred to as clonal expansion. The geographical limitations of clonal expansion, however, have not been adequately addressed. For example, it is not known whether a neoplastic clone from the oral cavity, pharynx, or larynx can migrate to the esophagus. We compared paired tumors from 16 patients with HNSCC and a second squamous cell carcinoma of the esophagus (ESCC) for patterns of allelic loss on chromosomal arms 3p, 9p, and 17p. Losses at these loci occur early during neoplastic transformation of the respiratory tract. In 14 cases (87%), the paired tumors had discordant patterns of allelic loss, suggesting that these tumors were not clonally related. Conversely, two (13%) of the 16 paired tumors had identical genetic alterations, which suggests clonal expansion as the mechanism underlying tumor multifocality. One clone spread from the hypopharynx into the cervical esophagus, and the other spread from the tonsil to the distal esophagus. Although most second ESCCs appear to arise as independent neoplasms, a clonal population of neoplastic cells is capable of traveling across substantial distances to give rise to second tumors at different anatomical sites.

Detection of head and neck squamous cell carcinoma among exfoliated oral mucosal cells by microsatellite analysis.

Prompt detection of head and neck squamous cell carcinoma (HNSCC) is vital to successful patient management. In this feasibility study, we used microsatellite analysis to detect tumor-specific genetic alterations in exfoliated oral mucosal cell samples from patients with known cancer. Exfoliated mucosal cells in pretreatment oral rinse and swab samples were collected from 44 HNSCC patients and from 43 healthy control subjects (20 nonsmokers and 23 smokers). We tested a panel of 23 informative microsatellite markers to assay DNA from the matched lymphocyte, tumor (from cancer cases), and oral test samples. Loss of heterozygosity or microsatellite instability of at least one marker was detected in 38 (86%) of 44 primary tumors. Identical alterations were found in the saliva samples in 35 of these 38 cases (92% of those with markers; 79% overall) including 12 of 13 cases with small primaries [stage Tt or Tx (occult primary)] and 4 of 4 cases of patients that had undergone prior radiation. Microsatellite instability was detectable in the saliva in 24 (96%) of 25 cases in which it was present in the tumor, and loss of heterozygosity was identified in the test sample in 19 (61%) of 31 cases. No microsatellite alterations were detected in any of the samples from the healthy control subjects. This approach must now be refined and validated for the detection of clinically occult disease. Microsatellite analysis of oral samples may then become a valuable method for detecting and monitoring HNSCC.