British Medical Journal (Clinical research ed.)最新文献

{"title":"Detailed Study of HPRT1 Gross Deletions Found in 10 Italian Lesch-Nyhan Families","authors":"","doi":"10.33140/mcr.06.06.06","DOIUrl":"https://doi.org/10.33140/mcr.06.06.06","url":null,"abstract":"Background: Lesch-Nyhan disease (LND) is an X-linked rare pathology involving the purine nucleotides salvage pathway. Its incidence is estimated in 1:350.000 born. The condition is due to mutations in the HPRT1 (hypoxanthine phosphoribosyl transferase 1) gene of which in our cohort 28% (10/35) are large deletions. In order to better assess the nature of the observed deletions in our LND population we analyzed 10 families carrying large deletions in the HPRT1 gene region and studied the underlying pathogenic mechanisms. Methods: We performed PCR based localization of the break points and sequenced the gap-junction fragments. Bioinformatics analysis was performed through several web tools on the 5’ and 3’ break points to determine the factors involved in the deletion mechanism. Results: We precisely mapped 10 unique large deletions involving the HPRT1 gene region that span from 300 bp to 64 kbp. No common breakpoints were found and each deletion appears to be family specific. Conclusions: The deletions in the HPRT1 gene area are consistent with the Micro homology-Mediated Break-Induced Replication (MMBIR) mechanism. There are strong links with Alu-s and no recurrent break points with all of the observed deletions being unique. The relatively large amount of deletions in the HPRT1 region is peculiar and linked with the almost absolute lack of polymorphic sites in the HPRT1 gene making it a very interesting region for further studies.","PeriodicalId":9304,"journal":{"name":"British Medical Journal (Clinical research ed.)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82521253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Attachment-Based Treatment for Anxiety Disorders Use of spontaneity as a mode of relating to resolve anxiety","authors":"","doi":"10.33140/mcr.06.06.04","DOIUrl":"https://doi.org/10.33140/mcr.06.06.04","url":null,"abstract":"Although we have established effective treatments for anxiety disorders,the problem is on the rise worldwide, and the effect sizesfor treatments suggest that advancements are needed. Part of the reason for the limitations in our treatments may be because they are designed to address the disorder’s symptoms rather than its underlying cause. This paper is geared toward presenting a likely neurobiological cause and a proposed treatment. There is significant evidence that the basis for anxiety is a combination of stress, especially interpersonal stress, and an inability to find solutions to resolve it. Anxiety is the result of this lack of coping ability. The part of the brain involved in designing these coping strategies, especially when the stressor is complex and emotion-based, is the dorsolateral prefrontal cortex. That is because it is the brain’s “sketch pad,” in that it allows us to think of solutions on a “symbolic” rather than a concrete basis.Anxiety arises when the person is unable to use this brain region effectively in formulating solutions, and instead designs ineffective solutions. The reason for that deficit may stem from early childhood, during a phase of attachment in which parents do not engage spontaneously in child-induced play. The mother is unable to be spontaneous in sharing the child’s play,which is needed for the child to generate his or her own solutions to problems. This leads to an inability of the child’s dorsolateral prefrontal cortex structure to properly develop. This will manifest as a lack of “insight,” or ability to generate spontaneous solutions to problems instead focusing on routinized solutions to emotion-based problems later in life that often do not work. Evidence is provided in a case report of a patient with an anxiety disorder who could not solve his interpersonal problems because he lacked the necessary insight. This deficit was so profound that he could not use insight-based psychotherapy and found use of medication too sedating. By modelling a more spontaneous give and take between the therapist and the patient’s wife, who served as a “co-therapist,”the patient was able to learn to develop his own insight. His wife would tell the therapist the problems the patient was unable to tell him and would help the patient to learn to respond to the interpretations offered by the therapist. The patient learned how to imitate his wife and describe his problems, and then to imitate the therapist and generate his own insight. As this occurred, his anxiety was resolved. The basis of the attachment that developed with his therapists was based on the use of spontaneity, from which the patient learned his own insights resolving his anxiety.","PeriodicalId":9304,"journal":{"name":"British Medical Journal (Clinical research ed.)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78175168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Camelid Antibodies May well be effective Against SARS-CoV-2 variants","authors":"Samir Djemli, A. Tahraoui, M. Boussena, Faiza Rouag, Ines Refes, S. Messikh, Ibtissem, Chouba, M. Kouadria, Rouya Memouni","doi":"10.33140/mcr.06.06.10","DOIUrl":"https://doi.org/10.33140/mcr.06.06.10","url":null,"abstract":"Are camels at the origin of a new treatment against Covid-19? What is certain is that these animals have small antibodies, absent in humans, which neutralize SARS-CoV-2 and some of its variants, according to Australian scientists.","PeriodicalId":9304,"journal":{"name":"British Medical Journal (Clinical research ed.)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87729428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Croatia’s First Experiences in Cytological Diagnosis of High-Grade Ductal Carcinoma in Situ of the Breast: Case Reports and a Review of Literature","authors":"","doi":"10.33140/mcr.06.06.12","DOIUrl":"https://doi.org/10.33140/mcr.06.06.12","url":null,"abstract":"Cases here presented are also first Croatia’s experiences in the cytological diagnosis of breast ductal carcinoma in situ (DCIS). The first patient was a 64-year-old woman, by imaging methods with a wide area of suspect microcalcifications in the left breast lower medial quadrant and abundant, dense, yellow-greyish discharge of the same mammilla and second was a 65-year-old woman with an equivocal lesion in left breast lower lateral quadrant. Morphological findings of both aspirates and nipple discharge from the first patient were practically the same - moderately to highly cellular, with 3D solid aggregates, monolayer sheets and many scattered single clearly malignant cells of large - mainly >5x the diameter of an erythrocyte, round-to-ovaloid, manifestly irregular nuclei, dark blue, polymorphous, often multiple (macro)nucleoli, irregular nuclear outlines and dense, more basophilic, mostly scant cytoplasms arranged in syncytium–like structures. “Dirty” background was overfull of comedo necrosis and dark grayish, sharp, irregular microcalcifications. Cytological diagnosis in both cases was DCIS, high-grade, comedo type. Histopathologically first tumor was big, 6 cm large, estimated as comedo carcinoma with microinvasion focuses not bigger than 1 mm, but without signs of angioinvasion, while the second tumor was smaller, 0.6 cm with wide ducts fully with large polymorphic malignant epithelial cells, central comedo necrosis, cancerisation of some lobules but with the intact basement membrane. It was pure high-grade DCIS, comedo type. Presented cases completely reflect to date knowledge about cytological diagnostic of high-grade DCIS; include necessary morphological criteria - highgrade nuclear atypia, an abundance of comedo necrosis and microcalcifications, confirm our limitation in the presumption of invasion status with large lesion extent, but also prove that cytology is the unquestionably reliable in breast morphological diagnostic, even in such sophisticated and demanding pathological issue like DCIS.","PeriodicalId":9304,"journal":{"name":"British Medical Journal (Clinical research ed.)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91379624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gender differences and trends of attitude toward physical activity in population aged 25- 64 years from 1988 to 2017","authors":"Article, V. Gafarov, D. Panov, E. Gromova, EA Krymov, I. Gagulin, A. Gafarova","doi":"10.33140/mcr.06.06.02","DOIUrl":"https://doi.org/10.33140/mcr.06.06.02","url":null,"abstract":"The aim: To determine gender differences in the dynamic of attitude toward physical activity in an open population of 25-64 years over a long-term period - 29 years in Russia / Siberia (Novosibirsk). Methods: Within the framework of the screening in 1988-89 under the WHO MONICA-psychosocial (MOPSY) program (n=1676, 49.5% males, mean age 44.1±0.4 years), in 2003-2005 under the international project HAPIEE (n=1650, 34.9% males, mean age 54.25±0.2 years), in 2013-2016 (n=975, 43.8% males, mean age 34.5±0,4 years) and 2016-2017 (n=663, 41.3% years 51.95±0.32 years) within the framework of the budgetary theme No. AAAA-A17-117112850280-2, random representative samples of men and women in one of districts in Novosibirsk were examined. Physical activity assessed by questionnaire proposed by MONICA-MOPSY protocol. Results: Men were 2 times more likely than women to report that they did not need to do physical exercises in 1988. In 2013- 2016, the proportion of young men and women who regularly did physical exercises increased significantly: 28.7% and 21.4%, respectively. In 2017, this trend continued among women but there were fewer men who regularly train. 59.9% of men and 73.1% of women aged 25-64 in 1988 reported “failed” attempts to exercise regularly. By 2017, the share of such men has not changed but for women it decreased to 7%. Women more often than men (30.3% vs 24.6%) spent their leisure time physically actively in 1988. By 2017, there was a tendency towards an increase in women aged 25-34 years with passive pastime to 21.1% and among men their share did not change. In 1988, the proportion of those who became less mobile during the year increased linearly with age, reaching 31.5% for men and 38.8% for women 55-64 years old. In 2017, the proportion of men and women who became less mobile decreased in comparison with 1988 and 2003 (11.6% and 22.2%, respectively; p <0.05). In 1988, women more often than men considered themselves insufficiently active. In 2013-2017, individuals of both sexes began to report more often that they are physically more active than other people of their own age. Males aged of 25-44 years considered themselves as active more often than females. But in the older age groups there was an increase in physical activity among women. Conclusions: There is an essential decline in physical activity with age but trends in self-rated levels of physical activity show a steady increase from 1988 to 2017, predominantly in women.","PeriodicalId":9304,"journal":{"name":"British Medical Journal (Clinical research ed.)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79800806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gender differences and trends of attitude toward smoking and diet behavior in population aged 25-64 years from 1988 to 2017","authors":"","doi":"10.33140/mcr.06.06.03","DOIUrl":"https://doi.org/10.33140/mcr.06.06.03","url":null,"abstract":"The aim: To determine gender differences in the dynamic of attitude toward smoking and diet behavior in an open population of 25-64 years over a long-term period - 29 years in Russia / Siberia (Novosibirsk). Methods: Within the framework of the screening in 1988-89 under the WHO MONICA-psychosocial (MOPSY) program (n=1676, 49.5% males, mean age 44.1±0.4 years), MOPSY screening in 1994-95 (n=1527, 43% males, mean age 44.85 ± 0.4 years), in 2003-2005 under the international project HAPIEE (n=1650, 34.9% males, mean age 54.25±0.2 years), in 2013-2016 (n=975, 43.8% males, mean age 34.5±0,4 years) and 2016-2017 (n=663, 41.3% years 51.95±0.32 years) within the framework of the budgetary theme No. AAAA-A17-117112850280-2, random representative samples of men and women in one of districts in Novosibirsk were examined. Smoking status and diet behavior assessed by questionnaire proposed by MONICA-MOPSY protocol. Results: The proportion of men who ever smoked was extremely high (80%) in the general population of 25-64 years and remained unchanged in the period 1988-2003 but began to decrease in 2013, first in the younger age groups and in 2016- 2017 in the older age groups. Despite the fact that there are significantly fewer female smokers, the proportion of female smokers began to increase in 1994, firstly in younger age groups and by 2003-05 in older age groups. Men of younger age groups more often than women tried unsuccessfully to give up a harmful habit. But in 2013-2016, the proportion of those who quit smoking increased to 25-29%. Men were 1.5-2 times more likely than women to report that they did not need to follow a diet. The number of those adhering to the diet, despite the increase in 2013-17, on average did not exceed 10% during 29 years of observation. Diet men were absent in the younger age group in 1988; but in the 45-54 age group their number reached a maximum of 17.1% in 2016-17, overtaking women in this indicator. The proportion of unsuccessful dietary attempts was higher among women in all age groups. The gender gap in the frequency of failed attempts to follow a diet has been growing since 2003. And in 2013-16, more than half of the male and 2/3 of the female population were unsuccessful in trying to adhere to the diet. Conclusions: There was a trend towards a decrease in smoking among men and, at the same time, a decrease in the proportion of women who never smoked in the period from 1994 to 2017. More than half of the male population and 2/3 of the female population were unsuccessful in trying to adhere to the diet, so the proportion of those following the diet did not exceed 10% during 29 years of observation.","PeriodicalId":9304,"journal":{"name":"British Medical Journal (Clinical research ed.)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74461435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cytological Differentiation of Ductal Carcinoma in Situ and Invasive Ductal Carcinoma of the Breast: A Personal View and a Literature Review","authors":"","doi":"10.33140/mcr.06.06.13","DOIUrl":"https://doi.org/10.33140/mcr.06.06.13","url":null,"abstract":"Although some find it controversial, it is possible to differentiate breast ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) using cytology only, with certain limitations. Invasiveness is the consequence of specific biological, i.e. aggressiveness potential of malignant cells, which is different with respect to the pre-existent DCIS, consequentially with different morphology. During the invasion, malignant cells go through multiple morphological changes, losing their epithelial and acquiring mesenchymal features in the fantastic process of epithelial-mesenchymal transition, which explains their morphology in cohabitation with the environment, includes the disruption of intercellular junctions, the increase of mobility and the release of the original epithelium. This mesenchymal-like phenotype supports the migration and invasion of cells, i.e. thus epithelial-mesenchymal transition ensures the tumor dissemination and metastasizing. Therefore, invasiveness can cytologically be “measured” by detecting morphological signs of increase of biological aggressiveness of malignant cells – through the change of their appearance (cytoplasm elongation in malignant squamous cells, i.e. in adenocarcinoma intracytoplasmic lumina, atypical nucleoli, coarsely clumped chromatin, eu-/parachromatin), but also with stromal parameters (disruption of the intercellular matrix, elastin fragments, capillaries endothelium) presented by tumour diathesis, fibroblast proliferation, fragments of elastoid stroma, invasion of connective and/or adipose tissue by groups and individual malignant cells. For the invasion are also very predictive tubular malignant structures, irregular angulated clusters of reduced cohesiveness, absence of benign naked nuclei, polymorph single tumour cells, less myoepithelial cells on tumour groups, fewer microcalcifications and foamy macrophages. Opposite morphological findings suggest DCIS. Even though cytologically we do not see and cannot see the basement membrane, highly likely we can predict the invasion – necessarily and always with the triple-diagnostic approach or clinical-radiological-morphological correlation to every breast lesion, in the representative well cellular sample and with good knowledge of patohistology and cytology","PeriodicalId":9304,"journal":{"name":"British Medical Journal (Clinical research ed.)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88160020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Management of Balance and Proprioception Discrepancies for a Patient with Cervicogenic Headache: A Case Report","authors":"","doi":"10.33140/mcr.06.06.01","DOIUrl":"https://doi.org/10.33140/mcr.06.06.01","url":null,"abstract":"Introduction: Previous research studies have established a link between cervical dysfunction, proprioception, and balance deficits in patients with cervicogenic headache. However, no current research exists to determine if the implementation of a balance program for these patients has any effect on their balance and proprioception capabilities. This case study aimed to identify if significant changes can be made the overall balance of a patient with cervicogenic headache as measured by the NeuroCom Sensory Organization Test. Case Description: The patient was a 50-year-old female, who had been suffering from long term cervicogenic headaches with increasing frequency and intensity for 6 months. Outcomes: The patient was seen for six visits over six weeks for balance training in addition to traditional physical therapy interventions including manual therapy and therapeutic exercise. After 6 sessions the patient made an overall improvement in balance (+7.9%) measured via the NeuroCom Sensory Organization Test and clinically significant improvements in reported pain via the Headache Disability Index (91.6%), Neck Disability Index (63.6%) and the Visual Analog Scale (2.5 points). Discussion: This case report demonstrates when balance training is added to standard manual therapy interventions for the management of cervicogenic headache you can successfully improve overall balance control measured with the NeuroCom Sensory Organization Test. Further research is necessary to further validate balance programming as a key intervention strategy for the general population with cervicogenic headache and guide decision-making for these patients.","PeriodicalId":9304,"journal":{"name":"British Medical Journal (Clinical research ed.)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81319718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cancer Treatment with Per Os Administered Methotrexate","authors":"","doi":"10.33140/mcr.06.02.04","DOIUrl":"https://doi.org/10.33140/mcr.06.02.04","url":null,"abstract":"As new anticancer agents are tried cancer treatment, the author remembered complete remission of choriocarcinoma and metastases with methotrexate (MTX) administered within some months, to get normal uterine pregnancy and usual life, thus wondered non-sergical MTX treatment of human common cancer, and several cancer treatments in Pubmed and NIH reports with success. The amount of chorioarcinoma therapy by MTX was 0.45 mg / kg /day, 200mg in a week, inserting some days’ rest, and repeated some months to get the full necrosis of uterine primary focus and metastases in my complete remission.","PeriodicalId":9304,"journal":{"name":"British Medical Journal (Clinical research ed.)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89913360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Apocrine Breast Carcinoma - Pathohistological And Immunohistochemical Analysis, Prognosis and Complex Treatment","authors":"","doi":"10.33140/mcr.06.02.02","DOIUrl":"https://doi.org/10.33140/mcr.06.02.02","url":null,"abstract":"Apocrine breast cancer (ABC) is a rarely diagnosed pathomorphological subtype of invasive ductal carcinoma of the breast. We present a clinical case of apocrine breast cancer in a 36-year-old woman. A left-sided breast-preserving surgery (quadrantectomy am blok with underlying muscle fascia) and axillary lymph dissection at all three levels were performed. The complex treatment is continued with adjuvant chemotherapy, followed by radiotherapy of the left mammary gland. The pathomorphological and immunohistochemical characteristics of apocrine breast cancer, the prognosis and the necessary complex treatment are discussed. Immunohistochemical (IHC) analysis of apocrine carcinoma cells reported a characteristic steroid receptor profile with negative IHC expression for estrogen and progesterone receptors and positive for androgen receptors. ABC is prognostically similar to invasive ductal carcinoma / NOS. Apocrine breast cancer needs to be classified as a separate nosological unit, due to growing evidence of a different hormonal profile with different clinical behavior following androgen deprivation therapy.","PeriodicalId":9304,"journal":{"name":"British Medical Journal (Clinical research ed.)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74164353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}