Aspergillus brasiliensis E_15.1: A Novel Thermophilic Endophyte from a Volcanic Crater Unveiled through Comprehensive Genome-Wide, Phenotypic Analysis, and Plant Growth-Promoting Trails.

Thermophilic fungi have been seldom studied despite the fact that they can contribute to understanding ecological mechanisms of adaptation in diverse environments and have attractive toolboxes with a wide range of biotechnological applications. This work describes for the first time an endophytic and thermophilic strain of Aspergillus brasiliensis that was isolated in the crater of the active volcano "El Chichonal" in Mexico. This strain was capable of surviving in soil with a temperature of 60 °C and a pH of neutral acidity, which preluded a high thermostability and a potential in industrial application. The complete genome of A. brasiliensis E_15.1 was sequenced and assembled in 37 Mb of genomic DNA. We performed a comprehensive phylogenomic analysis for the precise taxonomic identification of this species as a novel strain of Aspergillus brasiliensis. Likewise, the predicted coding sequences were classified according to various functions including Carbohydrate-Active Enzymes (CAZymes), biosynthetic gene clusters of secondary metabolites (BGCs), and metabolic pathways associated with plant growth promotion. A. brasiliensis E_15.1 was found to degrade chitin, chitooligosaccharides, xylan, and cellulose. The genes to biosynthesize clavaric acid (a triterpene with antitumor activity) were found, thus probably having antitumor activity. In addition to the genomic analysis, a set of enzymatic assays confirmed the thermostability of extracellular xylanases and cellulases of A. brasiliensis E_15.1. The enzymatic repertoire of A. brasiliensis E_15.1 suggests that A. brasiliensis E_15.1 has a high potential for industrial application due to its thermostability and can promote plant growth at high temperatures. Finally, this strain constitutes an interesting source of terpenoids with pharmacological activity.

Anthropometric study of the scapula in a contemporary population from granada. Sex estimation and glenohumeral osteoarthritis prevalence.

Anthropometric studies of the scapula have been rare in Spanish populations, nevertheless they are of current interest in forensic anthropology for estimation of sex. Although the estimation of sex is usually carried out on the pelvis and skull, other measurements related to the scapula can be helpful when the skeletal remains are incomplete. Glenohumeral osteoarthritis development is influenced, among others, by the morphology of the scapula, which is one of the less studied aspects. We carried out a descriptive study of anthropometric parameters in a series of 157 scapulae (82 individuals) on bone remains dated to the 20th century from a population of Granada (Southern Spain). Seventy seven (49%) were right-side and 80 (51%) left-side; 72 (45.9%) were from males and 85 (54.1%) from females, and the mean age at death was 70.76±11.7 years. The objective was to develop a discrimination function for sex estimation based on anthropometric parameters of the scapula other than those considered to date, and to analyze the prevalence of glenohumeral osteoarthritis in relation to selected anthropometric parameters. A logistic regression model based on parameters of the upper-external segment of the scapula was done. The obtained formula: 1/1+e^ (- (-57.911 + 0.350*B + 0283*C + 0.249*b + 0.166*a +-0.100*ß) classifies male sex with 98.3% accuracy and female sex with 92.1%. Glenohumeral osteoarthritis was detected in 16.6% of individuals and was related to age (p<0.05), scapular length (p<0.05), glenoid width (p<0.05), glenopolar angle (p<0.05), and α angle (p<0.05) in bivariate analyses but showed no significant associations in multivariate analyses. This approach can be useful for anthropological-forensic identification when scapula remains are incomplete. Glenohumeral osteoarthritis is significantly associated with a smaller α angle.

Semi-quantitative analysis with 99mTc-Besilesomab in musculoskeletal system infections.

Objectives: To evaluate the usefulness of 99mTc-Besilesomab to diagnose infectious processes by using monoclonal antibodies BW 250/183 in a semi-quantitative analysis, and to determine the effect on diagnostic capacity of different thresholds for the difference between counts in early versus delayed images. Methods: The study included 77 patients with suspected osteomyelitis who underwent scintigraphy with 99mTc-Besilesomab. After confirming the absence of human anti-mouse antibodies in all patients, early and delayed static images were acquired at 4 and 24 h post-injection, respectively. Visual and semi-quantitative analyses were conducted of regions of interest (ROIs) in areas suspected of infection on early and delayed images. Findings were considered positive when the ratio between counts in delayed and early images exceeded a given threshold after correction for decay. The definitive diagnosis was obtained by clinical follow-up, microbiological culture, or response to medical and/or surgical treatment. Results: The optimal threshold was 1.02 (i.e., positive result = count increase of >2 % in delayed image), obtaining a sensitivity of 0.864, specificity of 0.858, positive predictive value of 0.708, negative predictive value of 0.940, and accuracy of 0.860. Application of the usual threshold of 1.10 (10 %) reduced the sensitivity to 0.734. Conclusion: Semi-quantitative analysis of studies with 99mTc-Besilesomab is a useful technique for the diagnosis of musculoskeletal system infections and contributes to the definitive diagnosis when visual assessments are doubtful or non-conclusive.

Methemoglobinemia in Hemodialysis Patients due to Acute Chlorine Intoxication: A Case Series Calling Attention on an Old Problem.

INTRODUCTION: Hemodialysis uses municipal water that must be strictly purified and sterilized to be used for that procedure. Large amounts of decontaminants are often used, such as chlorine, and if these compounds are not subsequently removed they can be transferred to the blood of patients causing complications including methemoglobinemia. METHODS: In this case series study, dialysis patients in one unit were evaluated. We reviewed clinical characteristics and laboratory findings obtained on the day when the water supply was disinfected with chlorine, with the aim to quantify methemoglobin concentrations. Our objective was to characterize the clinical presentation and management of patients who presented with methemoglobinemia on a specific index day. We also reviewed reported cases in the literature regarding this underreported complication. RESULTS: Eight patients who presented with chlorine intoxication were evaluated. The methemoglobin concentrations were between 1.3% and 7.9% (reference value 0-1%). We believe this to be caused by water containing 0.78 mg/L of total chlorine. Seven patients presented with cyanosis, 4 with dizziness, 6 with dark brown blood, 4 with dyspnea, and 4 with headache and hemolytic anemia. Subjects were treated with supplemental oxygen, methylene blue, intravenous vitamin C, blood transfusions, and increased doses of erythropoietin. No patient died, and all continued with their usual hemodialysis sessions. CONCLUSION: Acute chlorine intoxication transferred by the water used during hemodialysis sessions can present with methemoglobinemia accompanied by cyanosis, oxygen desaturation, and hemolytic anemia. Chlorine levels should be carefully monitored in the water used for hemodialysis treatment.

Metalloproteinases 1 and 3 as Potential Biomarkers in Breast Cancer Development.

Breast cancer continues to be one of the main causes of morbidity and mortality globally and was the leading cause of cancer death in women in Spain in 2020. Early diagnosis is one of the most effective methods to lower the incidence and mortality rates of breast cancer. The human metalloproteinases (MMP) mainly function as proteolytic enzymes degrading the extracellular matrix and plays important roles in most steps of breast tumorigenesis. This retrospective cohort study shows the immunohistochemical expression levels of MMP-1, MMP-2, MMP-3, and MMP-9 in 154 women with breast cancer and 42 women without tumor disease. The samples of breast tissue are assessed using several tissue matrices (TMA). The percentages of staining (≤50%->50%) and intensity levels of staining (weak, moderate, or intense) are considered. The immunohistochemical expression of the MMP-1-intensity (p = 0.043) and MMP-3 percentage (p = 0.018) and intensity, (p = 0.025) present statistically significant associations with the variable group (control-case); therefore, expression in the tumor tissue samples of these MMPs may be related to the development of breast cancer. The relationships between these MMPs and some clinicopathological factors in breast cancer are also evaluated but no correlation is found. These results suggest the use of MMP-1 and MMP-3 as potential biomarkers of breast cancer diagnosis.

Tumor Escape Phenotype in Bladder Cancer Is Associated with Loss of HLA Class I Expression, T-Cell Exclusion and Stromal Changes.

Cancer eradication and clinical outcome of immunotherapy depend on tumor cell immunogenicity, including HLA class I (HLA-I) and PD-L1 expression on malignant cells, and on the characteristics of the tumor microenvironment, such as tumor immune infiltration and stromal reaction. Loss of tumor HLA-I is a common mechanism of immune escape from cytotoxic T lymphocytes and is linked to cancer progression and resistance to immunotherapy with the inhibitors of PD-L1/PD-1 signaling. Here we observed that HLA-I loss in bladder tumors is associated with T cell exclusion and tumor encapsulation with stromal elements rich in FAP-positive cells. In addition, PD-L1 upregulation in HLA-I negative tumors demonstrated a correlation with high tumor grade and worse overall- and cancer-specific survival of the patients. These changes define common immuno-morphological signatures compatible with cancer immune escape and acquired resistance to therapeutic interventions across different types of malignancy. They also may contribute to the search of new targets for cancer treatment, such as FAP-expressing cancer-associated fibroblasts, in refractory bladder tumors.

Role of Exocrine and Endocrine Insufficiency in the Management of Patients with Chronic Pancreatitis.

BACKGROUND: Exocrine pancreatic insufficiency results from the destruction of the pancreatic parenchyma and is diagnosed by using direct or indirect tests, both of which have shortcomings. Chronic pancreatitis is the most frequent cause of this pathology in adults. METHODS: Patients meeting radiological or histological diagnostic criteria of chronic pancreatitis are enrolled and the stool elastase test is conducted, considering fecal elastase levels >200 µg/g to represent normal pancreatic function, and levels <200 µg/g to indicate the presence of exocrine pancreatic insufficiency. Additionally, we determine the body mass index of the patients and study their nutritional status and main biochemical and hematological variables, including their glucose and hemoglobin A1c (HbA1c) levels. RESULTS: Exocrine pancreatic insufficiency is detected in 60% of the patients. Among these, 83.3% are severe cases, and 72% of the latter also are diagnosed with endocrine pancreatic insufficiency (diabetes mellitus). During the nutritional status study, HbA1c levels are significantly higher, and magnesium and prealbumin levels are significantly lower in patients with exocrine pancreatic insufficiency than in those without this disease. CONCLUSIONS: Exocrine and endocrine pancreatic insufficiency are highly prevalent among patients with chronic pancreatitis and an early diagnosis of these diseases is vital to improve the clinical management of these patients and reduce their risk of mortality.

miRNAs as radio-response biomarkers for breast cancer stem cells.

In breast cancer (BC), the presence of cancer stem cells (CSCs) has been related to relapse, metastasis, and radioresistance. Radiotherapy (RT) is an extended BC treatment, but is not always effective. CSCs have several mechanisms of radioresistance in place, and some miRNAs are involved in the cellular response to ionizing radiation (IR). Here, we studied how IR affects the expression of miRNAs related to stemness in different molecular BC subtypes. Exposition of BC cells to radiation doses of 2, 4, or 6 Gy affected their phenotype, functional characteristics, pluripotency gene expression, and in vivo tumorigenic capacity. This held true for various molecular subtypes of BC cells (classified by ER, PR and HER-2 status), and for BC cells either plated in monolayer, or being in suspension as mammospheres. However, the effect of IR on the expression of eight stemness- and radioresistance-related miRNAs (miR-210, miR-10b, miR-182, miR-142, miR-221, miR-21, miR-93, miR-15b) varied, depending on cell line subpopulation and clinicopathological features of BC patients. Therefore, clinicopathological features and, potentially also, chemotherapy regimen should be both taken into consideration, for determining a potential miRNA signature by liquid biopsy in BC patients treated with RT. Personalized and precision RT dosage regimes could improve the prognosis, treatment, and survival of BC patients.

Tumor genetic alterations and features of the immune microenvironment drive myelodysplastic syndrome escape and progression.

The transformation and progression of myelodysplastic syndromes (MDS) to secondary acute myeloid leukemia (sAML) involve genetic, epigenetic, and microenvironmental factors. Driver mutations have emerged as valuable markers for defining risk groups and as candidates for targeted treatment approaches in MDS. It is also evident that the risk of transformation to sAML is increased by evasion of adaptive immune surveillance. This study was designed to explore the immune microenvironment, immunogenic tumor-intrinsic mechanisms (HLA and PD-L1 expression), and tumor genetic features (somatic mutations and altered karyotypes) in MDS patients and to determine their influence on the progression of the disease. We detected major alterations of the immune microenvironment in MDS patients, with a reduced count of CD4+ T cells, a more frequent presence of markers related to T cell exhaustion, a more frequent presence of myeloid-derived suppressor cells (MDSCs), and changes in the functional phenotype of NK cells. HLA Class I (HLA-I) expression was normally expressed in CD34+ blasts and during myeloid differentiation. Only two out of thirty-six patients with homozygosity for HLA-C groups acquired complete copy-neutral loss of heterozygosity in the HLA region. PD-L1 expression on the leukemic clone was also increased in MDS patients. Finally, no interplay was observed between the anti-tumor immune microenvironment and mutational genomic features. In summary, extrinsic and intrinsic immunological factors might severely impair immune surveillance and contribute to clonal immune escape. Genomic alterations appear to make an independent contribution to the clonal evolution and progression of MDS.

Speed of Retinal Vascularization in Retinopathy of Prematurity: Risk and Protective Factors.

OBJECTIVE: The objective was to study the risk and protective factors involved in retinal vascular development of preterm infants with retinopathy of prematurity. METHODS: Between 2000 and 2017, 185 preterm infants were included in the protocol for retinopathy of prematurity. Risk factors associated with speed of retinal vascularization <0.5 disc diameter/week were studied in each of them. RESULTS: The statistically significant variables related to retinal vascular development <0.5 DD/w were intubation days, degree 3 of bronchopulmonary dysplasia, weight gain at 4-6 weeks, avascular temporal area, gestational age, number of transfusions, sepsis, number of risk factors, apnea at birth, presence of ductus arteriosus, and days of continuous positive airway pressure therapy. After the multivariate logistic regression analysis, only three variables were found to be significant: intubation days (p=0.005), degree 3 of bronchopulmonary dysplasia (p=0.022), and weight gain at 4-6 weeks (p=0.031). CONCLUSION: In retinopathy of prematurity, degree 3 of bronchopulmonary dysplasia and intubation days cause delayed retinal vascular development, whereas greater postnatal weight gain favors an appropriate rate of retinal vascularization.

EFECTO DE DIFERENTES EXPLANTES IRRADIADOS EN LA REGENERACIÓN in vitro DE FRIJOL COMÚN (Phaseolus vulgaris L.) CULTIVAR "ICA Pijao" / Effect of Different Irradiated Explants in the in vitro Regeneration of Common Bean (Phaseolus vulgaris L.) Cultivar "ICA Pijao"

RESUMEN El mejoramiento genético convencional en frijol común resulta difícil debido a que presenta una base genética estrecha y muy estable. En este sentido, la combinación de la mutagénesis y el cultivo de tejidos, es una alternativa para inducir variabilidad genética en la búsqueda de tolerancia a factores bióticos y abióticos. Es por ello, que el presente trabajo tuvo como objetivo determinar el efecto de diferentes explantes irradiados en la regeneración in vitro de frijol común (Phaseolus vulgaris L.) cultivar "ICA Pijao". Se aplicaron radiaciones gamma en callos, en el nudo cotiledonal con un cotiledón (NC-1) con dosis de 0, 10, 20, 30, 40, 50 y 60 Gy y semillas con 0, 100, 200, 300 y 400 Gy. Se evaluó el porcentaje de germinación, longitud de las raíces, porcentaje de explantes que formaron callos, masa fresca (g) de los callos, número de brotes por callo y el número de brotes con raíces. La radiación gamma provocó una disminución en la masa fresca del callo y NC-1. Los callos y el NC-1 solamente formaron brotes con las dosis de 10 y 20 Gy, pero estos fueron hiperhíricos. Los resultados demostraron que la semilla irradiada fue el explante con el que se logró la regeneración in vitro de plantas con hojas definidas, por lo que se recomienda como explante inicial para el uso combinado de mutagénesis y regeneración in vitro de plantas para el cultivar P. vulgaris "ICA Pijao" a través de la organogénesis indirecta.

ABSTRACT Conventional breeding in common bean is difficult because they have a close and very stable genetic base. In this connection the combination of mutagenesis and tissue culture is an alternative to induce genetic variability in the search for tolerance to biotic and abiotic factors. For this reason, the present study aimed to determine the effect of different irradiated explants in the in vitro regeneration of common bean (Phaseolus vulgaris L.) cultivar "ICA Pijao". To do this, were applied doses gamma radiation in callus, cotiledonary node with one cotyledon (NC-1) with doses of radiation 0, 10, 20, 30, 40, 50 and 60 Gy and seeds with 0, 100, 200, 300 and 400 Gy. The length of roots in the germinated seeds, fresh mass (g) of the callus and the number of shoots per callus were determined. The gamma radiation caused a decrease in the fresh weight of callus and NC-1. The callus and NC-1, irradiated with doses of 10 and 20 Gy they formed buds but these were hyperhydric. Results demonstrated that the irradiated seed was the explant with which it was achieved regeneration of shoots with leaves defined, so it is recommended as initial explant for combined use of mutagenesis and in vitro regeneration of plants for P. vulgaris cultivar "ICA Pijao" via organogenesis indirect.

Promoting breast cancer awareness in older women during the seasonal flu vaccination campaign.

BACKGROUND:: older women are at high risk of presenting with breast cancer when it has reached a late stage, which may be partly because of poor breast cancer awareness. AIM:: the aim of this project was to implement and evaluate a new way of delivering the Promoting Early Presentation (PEP) Intervention during flu vaccination appointments in primary care. The PEP Intervention is a 1-minute intervention, accompanied by a booklet and delivered by primary care health professionals to provide older women with the knowledge, confidence and skills to present promptly on discovering symptoms of breast cancer. METHOD:: health professionals delivered the PEP Intervention to older women at six general practices in south London. The authors measured changes in breast cancer awareness after the intervention and interviewed practice staff about their experiences of using it. FINDINGS:: knowledge of breast symptoms and breast checking was greater in women aged 70 years and above after the implementation than before. Health professionals' found it acceptable and feasible to implement. CONCLUSION:: this intervention is a novel way of increasing breast cancer awareness in older women, which could contribute to earlier presentation and diagnosis of breast cancer in the UK.

Biology and predation capacity of Parasitus bituberosus (Acari: Mesostigmata: Parasitidae) on Frankliniella occidentalis (Thysanoptera: Thripidae), and free-living nematodes as its complementary prey.

BACKGROUND: Parasitus bituberosus is common in rose fields and nearby vegetation around Bogotá. In rearing units, it is often aggregated, feeding on Frankliniella occidentalis edaphic phases. Preliminary observations suggested predator immatures can not reach adulthood if isolated. The objectives were to evaluate the suitability of F. occidentalis as prey for P. bituberosus, to evaluate free-living nematodes as complementary food, and to confirm the aggregation effect on predator biology. Aggregation types: (1) isolated mites, (2) mites paired only as deutonymphs and early adulthood, and (3) mites always paired. Diets: thrips (T), nematodes (N) and thrips + nematodes (NT). RESULTS: Parasitus bituberosus juveniles did not feed on live F. occidentalis, but developed and oviposited on nematodes. Approximately 77% of the isolated mites died as immatures. Mortality was low (21-23%) when predators were paired at least in the deutonymph and the early adult phase. Female daily predation rates were comparable to other predators on F. occidentalis (≥2.5). Continuously paired mites had high biotic potential, especially when the diet included nematodes (rm  ≥ 0.33; Ro  ≥ 33.90; daily oviposition rate ≥ 10.9). CONCLUSION: The results of this study warrant further investigation of this predator, to evaluate methods for its mass production, inclusion in conservation biocontrol programs and performance against the pest at a larger scale. © 2019 Society of Chemical Industry.

HLA class I loss and PD-L1 expression in lung cancer: impact on T-cell infiltration and immune escape.

Immune-checkpoint inhibitors show encouraging results in cancer treatment, but the clinical benefit is limited exclusively to a subset of patients. We analyzed the density and composition of tumor T-cell infiltration in non-small-cell lung carcinoma (NSCLC) in relation to PD-L1 and HLA class I (HLA-I) expression. We found that positive HLA-I expression, independently on PD-L1 status, is the key factor determining the increased density of the immune infiltrate. When both markers were analyzed simultaneously, we identified four phenotypes of HLA-I and PD-L1 co-expression. They demonstrated different patterns of tumor infiltration and clinicopathologic characteristics, including the tumor size and lymphatic spread. All HLA-I+/PD-L1+ tumors had a high degree of intratumoral infiltration with CD8+T-lymphocytes, whereas HLA-I loss was associated with a significantly reduced number of tumor infiltrating T-lymphocytes mostly restrained in the stroma surrounding the tumor nest. HLA-I-negative/PD-L1-positive tumors had bigger size (T) and lower grade of infiltration with CD8+T-cells. It represents a cancer immune escape phenotype that combines two independent mechanisms of immune evasion: loss of HLA-I and upregulation of PD-L1. Using GCH-array analysis of human lung cancer cell lines we found that the loss of heterozygosity (LOH) with complete or partial deletion of HLA-I genes is the principal mechanism of HLA-I alterations. This irreversible defect, which could potentially decrease the clinical efficacy of lung cancer immunotherapy, appears to be underestimated. In conclusion, our results suggest that the analysis of HLA-I is very important for the selection of potential responders to cancer immunotherapy.

Three-dimensional analysis of third molar development to estimate age of majority.

Third molars are one of the few biological markers available for age estimation in undocumented juveniles close the legal age of majority, assuming an age of 18years as the most frequent legal demarcation between child and adult status. To obtain more accurate visualization and evaluation of third molar mineralization patterns from computed tomography images, a new software application, DentaVol©, was developed. Third molar mineralization according to qualitative (Demirjian's maturational stage) and quantitative parameters (third molar volume) of dental development was assessed in multi-slice helical computed tomography images of both maxillary arches displayed by DentaVol© from 135 individuals (62 females and 73 males) aged between 14 and 23years. Intra- and inter-observer agreement values were remarkably high for both evaluation procedures and for all third molars. A linear correlation between third molar mineralization and chronological age was found, with third molar maturity occurring earlier in males than in females. Assessment of dental development with both procedures, by using DentaVol© software, can be considered a good indicator of age of majority (18years or older) in all third molars. Our results indicated that virtual computed tomography imaging can be considered a valid alternative to orthopantomography for evaluations of third molar mineralization, and therefore a complementary tool for determining the age of majority.

"Promoting Early Presentation" intervention sustains increased breast cancer awareness in older women for three years: A randomized controlled trial.

Objective In a randomized controlled trial, the Promoting Early Presentation intervention increased older women's breast cancer awareness after two years. We investigated whether this increase was sustained at three years, and the effect on breast screening self-referral. Methods We randomly allocated 867 women attending their final invited breast screening appointment to the Promoting Early Presentation intervention or usual care. We examined breast cancer awareness after three years and breast screening self-referrals after four years. Results Women in the Promoting Early Presentation intervention arm had higher breast cancer awareness at three years than the usual care arm (odds ratio: 10.4; 95% confidence interval: 3.1 to 34.8). There were no differences in proportions self-referring for breast screening between arms, but statistical power was limited. Conclusion The Promoting Early Presentation intervention has a sustained effect on breast cancer awareness in older women. The effect on self-referral for breast screening is unclear.

Promoting early presentation of breast cancer in older women: sustained effect of an intervention to promote breast cancer awareness in routine clinical practice.

BACKGROUND: Older women have poorer survival from breast cancer, which may be at least partly due to poor breast cancer awareness leading to delayed presentation and more advanced stage at diagnosis. In a randomised trial, an intervention to promote early presentation of breast cancer in older women increased breast cancer awareness at 1 year compared with usual care (24 versus 4%). We examined its effectiveness in routine clinical practice. METHODS: We piloted the intervention delivered by practising health professionals to women aged about 70 in four breast screening services. We measured the effect on breast cancer awareness at 1 year compared with comparison services, where women did not receive the intervention. RESULTS: At 1 year, 25% of women in pilot services were breast cancer aware compared with 4% in comparison services (p = 0.001). The components of breast cancer awareness were knowledge of breast cancer non-lump symptoms (pilot: 63% vs comparison: 82% at 1 year; OR = 2.56, 95% CI 1.92-3.42), knowledge of age related risk (pilot: 8% vs comparison: 36% at 1 year; OR = 5.56, 95% CI 4.0-7.74) and reported breast checking (pilot: 70% vs comparison: 78% at 1 year; OR = 1.49, 95% CI 1.13-1.96). CONCLUSION: The intervention may be as effective in routine clinical practice as in a randomised controlled trial. This intervention has the potential to reduce patient delay in the diagnosis of breast cancer in older women. TRIAL REGISTRATION: The PEP trial was registered with the International Standard Registered Clinical/soCial sTudy Number (ISRCTN) as a clinical trial ( ISRCTN31994827 ) on 3rd October 2007.

Regeneration of fat cells from myofibroblasts during wound healing.

Although regeneration through the reprogramming of one cell lineage to another occurs in fish and amphibians, it has not been observed in mammals. We discovered in the mouse that during wound healing, adipocytes regenerate from myofibroblasts, a cell type thought to be differentiated and nonadipogenic. Myofibroblast reprogramming required neogenic hair follicles, which triggered bone morphogenetic protein (BMP) signaling and then activation of adipocyte transcription factors expressed during development. Overexpression of the BMP antagonist Noggin in hair follicles or deletion of the BMP receptor in myofibroblasts prevented adipocyte formation. Adipocytes formed from human keloid fibroblasts either when treated with BMP or when placed with human hair follicles in vitro. Thus, we identify the myofibroblast as a plastic cell type that may be manipulated to treat scars in humans.

Which symptoms are linked to a delayed presentation among melanoma patients? A retrospective study.

BACKGROUND: The incidence of melanoma is rising. Early detection is associated with a more favourable outcome. The factors that influence the timing of a patient's presentation for medical assessment are not fully understood. The aims of the study were to measure the nature and duration of melanoma symptoms in a group of patients diagnosed with melanoma within the preceding 18 months and to identify the symptoms and barriers associated with a delay in presentation. METHODS: A questionnaire was distributed to a random sample of 200 of the 963 melanoma patients who had participated in the Cancer Patient Experience Survey 2010 and were known to be alive 1 year later. Data were collected on symptoms, duration of symptoms prior to presentation and the reasons for not attending a doctor sooner. RESULTS: A total of 159 patients responded to the questionnaire; 74 (47%) were men; mean age was 62 (range 24-90) years. Of the 149 patients who reported a symptom, 40 (27%) had a delayed presentation (i.e. >3 months). A mole growing bigger was the most common symptom and reporting this symptom was significantly associated with a delayed presentation (odds ratio (OR) 2.04, 95% confidence interval (95% CI) 1.14-5.08). Patients aged ≥65 years were less likely to report a barrier to presentation and were less likely to delay than those under 40, although this was of borderline statistical significance (OR 0.28, 95% CI 0.08-1.00). CONCLUSIONS: This study highlights that an enlarging mole is a significant symptom influencing the timing of presentation. Increasing public awareness of the signs of melanoma and of the importance of early presentation is desirable. Health professionals should take advantage of the opportunity to educate patients on such symptoms and signs where feasible. Further exploration of the barriers to presentation in younger people should be considered.

Cochlear implantation in patients with inner ear bone malformations with posterior labyrinth involvement: an exploratory study.

Inner ear bone malformations are one cause of profound sensorineural hearing loss. This investigation focused on those affecting the posterior labyrinth, especially enlarged vestibular aqueduct syndrome, which is associated with fluctuating and progressive hearing loss. The objectives of this study were to analyze the behavior of the electrical stimulation, auditory functionality and linguistic development in patients with inner ear malformations involving the posterior labyrinth. The study included ten patients undergoing cochlear implantation (cases: five with enlarged vestibular aqueduct, two with vestibular aqueduct stenosis/aplasia, and three with semicircular canal disorders). Post-implantation, data were gathered on the electrical stimulation threshold and maximum comfort levels and on the number of functioning electrodes. Evaluation of Auditory Responses to Speech (EARS) subtests were used to assess auditory functionality and language acquisition at 6, 12, and 24 months post-implantation. Results were compared with findings in a control group of 28 cochlear implantation patients without these malformations. No significant differences were found between case and control groups in electrical stimulation parameters; auditory functionality subtest scores were lower in cases than controls, although the difference was only statistically significant for some subtests. In conclusion, cochlear implantation patients with posterior labyrinth bone malformations and profound hearing loss, including those with enlarged vestibular aqueduct syndrome, showed no significant difference in electrical stimulation threshold with controls. Although some auditory functionality test results were lower in cases than in controls, cochlear implantation appears to be beneficial for all patients with these malformations.