Cell-cell fusion is a normal biological process playing essential roles in organ formation and tissue differentiation,repair and regeneration.Through cell fusion somatic cells undergo rapid nuclear reprogramming and e...Cell-cell fusion is a normal biological process playing essential roles in organ formation and tissue differentiation,repair and regeneration.Through cell fusion somatic cells undergo rapid nuclear reprogramming and epigenetic modifications to form hybrid cells with new genetic and phenotypic properties at a rate exceeding that achievable by random mutations.Factors that stimulate cell fusion are inflammation and hypoxia.Fusion of cancer cells with non-neoplastic cells facilitates several malignancy-related cell phenotypes,e.g.,reprogramming of somatic cell into induced pluripotent stem cells and epithelial to mesenchymal transition.There is now considerable in vitro,in vivo and clinical evidence that fusion of cancer cells with motile leucocytes such as macrophages plays a major role in cancer metastasis.Of the many changes in cancer cells after hybridizing with leucocytes,it is notable that hybrids acquire resistance to chemo-and radiation therapy.One phenomenon that has been largely overlooked yet plays a role in these processes is polyploidization.Regardless of the mechanism of polyploid cell formation,it happens in response to genotoxic stresses and enhances a cancer cell’s ability to survive.Here we summarize the recent progress in research of cell fusion and with a focus on an important role for polyploid cells in cancer metastasis.In addition,we discuss the clinical evidence and the importance of cell fusion and polyploidization in solid tumors.展开更多
Background: Pituitary insufficiencies after traumatic brain injury (TBI) and subarachnoid haem-orrhage (SAH) have been reported with very varying frequencies. The aim of this study was to describe the pituitary functi...Background: Pituitary insufficiencies after traumatic brain injury (TBI) and subarachnoid haem-orrhage (SAH) have been reported with very varying frequencies. The aim of this study was to describe the pituitary function in the acute phase after TBI and SAH in a cohort of adults and relate the results to injury variables. Methods: Adults admitted to the neurointensive care unit in our hospital after moderate and severe TBI or SAH were included prospectively. Demographic, clinical, laboratory, including ACTH stimulation test, and radiological data were collected. Results: A total of 130 adults, 84 (19 women/65 men) with TBI and 46 (38 women/8 men) with SAH were included. Nine patients with TBI and six patients with SAH responded insufficiently to ACTH stimulation;14 patients with TBI and 9 patients with SAH had low fT4 and low-normal TSH levels. No relations were seen between hormonal levels and injury variables. Conclusions: Pituitary deficiencies occur after TBI and SAH, and a continuous endocrine evaluation of these patients is important. Our study could not define a marker for increased risk for pituitary deficiency. The long-term clinical outcome of the pathological hormone levels in the early phase after TBI and SAH is not known in detail and further studies to elucidate this are needed.展开更多
Previous published studies have shown an improvement of penile hemodynamic parameters after low-intensity extracorporeal shockwave therapy(Li-ESWT).However,the clinical significance of these findings remains unclear,a...Previous published studies have shown an improvement of penile hemodynamic parameters after low-intensity extracorporeal shockwave therapy(Li-ESWT).However,the clinical significance of these findings remains unclear,and definitive selection criteria for Li-ESWT based on preexisting comorbidities have yet to be established.This was an observational study of 113 patients with ED,evaluated between January 2019 and December 2021 in Andrology Unit at the Department of Urology and Renal Transplantation,University of Foggia(Foggia,Italy).Penile dynamic Doppler was performed to evaluate vascular parameters and 5-item version of the International Index of Erectile Dysfunction(IIEF-5)questionnaire was administered to assess the severity of ED.This was repeated 1 month after treatment.Patients with a peak systolic velocity(PSV)<30 cm s−1 were considered eligible for Li-ESWT.Our protocol consisted of 8 weekly sessions with 1500 strokes distributed in 5 different locations along the penis.After treatment,a significant mean(±standard deviation[s.d.])PSV increase of 5.0(±3.4)cm s−1 was recorded and 52/113(46.0%)patients reached a PSV>30 cm s−1 at posttherapeutic penile dynamic Doppler.A clinically significant IIEF-5 score improvement was observed in 7 patients,21 patients,and 2 patients with mild-to-moderate,moderate,and severe pretreatment ED,respectively.No different outcomes were assessed based on smoking habits,previous pelvic surgery,or use of oral phosphodiesterase-5 inhibitor(PDE5i).On the other side,only 1(6.7%)in 15 patients with diabetes mellitus showed an IIEF-5 score improvement after Li-ESWT.Shockwave treatment determined a significant increase in PSV and correlated IIEF-5 improvement in ED patients.This advantage seemed particularly evident for moderate ED and was not affected by smoking habits,previous pelvic surgery,and use of PDE5i.Conversely,diabetic patients did not benefit from the treatment.展开更多
AIM: To clarify the association between physical activity and gastroesophageal reflux disease (GERD) in nonobese and obese people. METHODS: A Swedish population-based cross-sectional survey was conducted. Participants...AIM: To clarify the association between physical activity and gastroesophageal reflux disease (GERD) in nonobese and obese people. METHODS: A Swedish population-based cross-sectional survey was conducted. Participants aged 40-79 years were randomly selected from the Swedish Registry of the Total Population. Data on physical activity, GERD, body mass index (BMI) and the covariates age, gender, comorbidity, education, sleeping problems, and tobacco smoking were obtained using validated questionnaires. GERD was self-reported and defined as heartburn or regurgitation at least once weekly, and having at least moderate problems from such symptoms. Frequency of physical activity was categorized into three groups: (1) "high" (several times/week); (2) "intermediate" (approximately once weekly); and (3) "low" (1-3 times/mo or less). Analyses were stratified for participants with "normal weight" (BMI < 25 kg/m 2 ), "overweight" (BMI 25 to ≤ 30 kg/m 2 ) and "obese" (BMI > 30 kg/m 2 ). Multivariate logistic regression was used to calculate odds ratios (ORs) with 95% confidence intervals (CIs), adjusted for potential confounding by covariates. RESULTS: Of 6969 eligible and randomly selected individuals, 4910 (70.5%) participated. High frequency of physical activity was reported by 2463 (50%) participants, GERD was identified in 472 (10%) participants, and obesity was found in 680 (14%). There were 226 (5%) individuals with missing information about BMI. Normal weight, overweight and obese participants were similar regarding distribution of gender and tobacco smoking status, while obese participants were on average slightly older, had fewer years of education, more comorbidity, slightly more sleeping problems, lower frequency of physical activity, and higher occurrence of GERD. Among the 2146 normal-weight participants, crude point estimates indicated a decreased risk of GERD among individuals with high frequency of physical activity (OR: 0.59, 95% CI: 0.39-0.89), compared to low frequency of physical activity. However, after adjustment for potential confounding factors, neither intermediate (OR: 1.30, 95% CI: 0.75-2.26) nor high (OR: 0.99, 95% CI: 0.62-1.60) frequency of physical activity was followed by decreased risk of GERD. Sleeping problems and high comorbidity were identified as potential confounders. Among the 1859 overweight participants, crude point estimates indicated no increased or decreased risk of GERD among individuals with intermediate or high frequency of physical activity, compared to low frequency. After adjustment for confounding, neither intermediate (OR: 0.75, 95% CI: 0.46-1.22) nor high frequency of physical activity were followed by increased or decreased risk of GERD compared to low frequency among nonobese participants. Sleeping problems and high comorbidity were identified as potential confounders for overweight participants. In obese individuals, crude ORs were similar to the adjusted ORs and no particular confounding factors were identified. Intermediate frequency of physical activity was associated with a decreased occurrence of GERD compared to low frequency of physical activity (adjusted OR: 0.41, 95% CI: 0.22-0.77). CONCLUSION: Intermediate frequency of physical activity might decrease the risk of GERD among obese individuals, while no influence of physical activity on GERD was found in non-obese people.展开更多
Repeated surveys from Europe, the United States, Australia, and New Zealand have shown that adherence to an evidence-based perioperative care protocol, such as Enhanced Recovery After Surgery(ERAS), has been generally...Repeated surveys from Europe, the United States, Australia, and New Zealand have shown that adherence to an evidence-based perioperative care protocol, such as Enhanced Recovery After Surgery(ERAS), has been generally low. It is of great importance to support the implementation of the ERAS protocol as it has been shown to improve outcomes after a number of surgical procedures, including major abdominal surgery. However, despite an increasing awareness of the importance of structured perioperative management, the implementation of this complex protocol has been slow. Barriers to implementation involve both patient- and staff-related factors as well as practice-related issues and resources. To support efficient and successful implementation, further educational and structural measures have to be made on a national or regional level to improve the standard of general health care. Besides postoperative morbidity, biological and physiological variables have been quite commonly reported in previous ERAS studies. Little information, however, has been obtained on cost-effectiveness, long-term outcomes, quality of life and patient-related outcomes, and these issues remain important areas of research for future studies.展开更多
AIM To systematically review the literature on women with both diabetes in pregnancy(DIP) and depression during or after pregnancy. METHODS In this systematic literature review, PubM ed/MEDLINE and EMBASE were searche...AIM To systematically review the literature on women with both diabetes in pregnancy(DIP) and depression during or after pregnancy. METHODS In this systematic literature review, PubM ed/MEDLINE and EMBASE were searched(13 November 2015) using terms for diabetes(type 1, type 2, or gestational), depression, and pregnancy(no language or date restrictions). Publications that reported on women who had both DIP(any type) and depression or depressive symptoms before, during, or within one year after pregnancy were considered for inclusion. All study types were eligible for inclusion; conference abstracts, narrative reviews, nonclinical letters, editorials, and commentaries were excluded, unless they provided treatment guidance.RESULTS Of 1189 articles identified, 48 articles describing women with both DIP and depression were included(sample sizes 36 to > 32 million). Overall study quality was poor; most studies were observational, and only 12 studies(mostly retrospective database studies) required clinical depression diagnosis. The prevalence of concurrent DIP(any type) and depression in general populations of pregnant women ranged from 0% to 1.6%(median 0.61%; 12 studies). The prevalence of depression among women with gestational diabetes ranged from 4.1% to 80%(median 14.7%; 16 studies). Many studies examined whether DIP was a risk factor for depression or depression was a risk factor for DIP. However, there was no clear consensus for either relationship. Importantly, we found limited guidance on the management of women with both DIP and depression. CONCLUSION Given the increasing prevalence of diabetes and depression, high-quality research and specific guidance for management of pregnant women with both conditions are warranted.展开更多
BACKGROUNDDiabetes mellitus causes a large majority of non-traumatic major and minoramputations globally. Patients with diabetes are clinically complex with amultifactorial association between diabetic foot ulcers (DF...BACKGROUNDDiabetes mellitus causes a large majority of non-traumatic major and minoramputations globally. Patients with diabetes are clinically complex with amultifactorial association between diabetic foot ulcers (DFU) and subsequentlower extremity amputations (LEA). Few studies show the long-term outcomeswithin the cohort of DFU-associated LEA.AIMTo highlight the long-term outcomes of LEA as a result of DFU.METHODSPubMed/MEDLINE and Google Scholar were searched for key terms, “diabetes”,“foot ulcers”, “amputations” and “outcomes”. Outcomes such as mortality, reamputation,re-ulceration and functional impact were recorded. Peer-reviewedstudies with adult patients who had DFU, subsequent amputation and follow upof at least 1 year were included. Non-English language articles or studiesinvolving children were excluded.RESULTSA total of 22 publications with a total of 2334 patients were selected against theinclusion criteria for review. The weighted mean of re-amputation was 20.14%,29.63% and 45.72% at 1, 3 and 5 years respectively. The weighted mean of mortality at 1, 3 and 5 years were 13.62%, 30.25% and 50.55% respectively withsignificantly higher rates associated with major amputation, re-amputation andischemic cardiomyopathy.CONCLUSIONPrevious LEA, level of the LEA and patient comorbidities were significant riskfactors contributing to re-ulceration, re-amputation, mortality and depreciatedfunctional status.展开更多
AIM: To perform a systematic review of reported neonatal and pregnancy outcomes of Indigenous Australians with diabetes in pregnancy(DIP).METHODS: Electronic searches of Pub Med and Web of Science were carried out. Ar...AIM: To perform a systematic review of reported neonatal and pregnancy outcomes of Indigenous Australians with diabetes in pregnancy(DIP).METHODS: Electronic searches of Pub Med and Web of Science were carried out. Articles were selected if they contained original data on DIP outcomes in Indigenous Australians. There were no specific exclusion criteria.RESULTS: A total of eight articles, predominantly from Queensland and Western Australia were identified once inclusion criteria were applied. Birth data from midwifery registries or paper charts encompassing years 1985-2008 were used. A total of 465591 pregnant women with and without DIP were included in the eight studies, with 1363 being Indigenous women with DIP. Indigenous Australians experienced increased rates of many known adverse outcomes of DIP including: macrosomia, caesarean section, congenital deformities, low birth weight, hypoglycaemia, and neonatal trauma. There were regional differences among Indigenous Australians, particularly regional/remote vs metropolitan populations where the regional/remote data showed worse outcomes. Two of the articles did not note a difference between Aboriginals and Caucasians in the rates of measured adverse outcome. Studies varied significantly in size, measured outcomes, and subsequent analysis.CONCLUSION: The health disparities between Indigenous Australians and non-Indigenous Australians are further evidenced by poorer outcomes in DIP. This has broader implications for Indigenous health in general.展开更多
Standard treatment for soft tissue sarcoma,based on complete surgical resection with or without adjuvant radiotherapy and chemotherapy,has not substantially changed during the last several decades.Nevertheless,recent ...Standard treatment for soft tissue sarcoma,based on complete surgical resection with or without adjuvant radiotherapy and chemotherapy,has not substantially changed during the last several decades.Nevertheless,recent advances have contributed to considerable improvement in the management of these patients;for example,new magnetic resonance imaging sequences such as diffusionweighted imaging and magnetic resonance imaging radiomics can better assess tumor extension and even estimate its grade.Detection of circulating genetic material(liquid biopsy)and next-generation sequencing are powerful techniques for genetic analysis,which will increase our understanding of the underlying molecular mechanisms and may reveal potential therapeutic targets.The role of chemotherapy in non-metastatic disease is still controversial,and there is a need to identify patients who really benefit from this treatment.Novel chemotherapeutic regimens have entered clinical praxis and can change the outcome of patients with metastatic disease.Advances in radiotherapy have helped decrease local adverse effects and sustain good local control of the disease.The following report provides an updated view of the diagnosis,treatment,and future perspectives on the management of patients with soft tissue sarcomas.展开更多
AIM: To study if the angiotensin II receptor blockers (ARB) losartan counteracts pancreatic hyperenzymemia as measured 24 h after endoscopic retrograde cholangiopancreatography (ERCP). METHODS: A triple-blind and plac...AIM: To study if the angiotensin II receptor blockers (ARB) losartan counteracts pancreatic hyperenzymemia as measured 24 h after endoscopic retrograde cholangiopancreatography (ERCP). METHODS: A triple-blind and placebo-controlled randomized clinical trial was performed at two Swedish hospitals in 2006-2008. Patients over 18 years of age undergoing ERCP, excluding those with current pancreatitis, current use of ARB, and severe disease, such as sepsis, liver and renal failure. One oral dose of 50 mg losartan or placebo was given one hour before ERCP. The relative risk of hyperenzymemia 24 h after ERCP was estimated using multivariable logistic regression, and expressed as odds ratio with 95% confidence intervals (CIs), including adjustment for potential remaining confounding. RESULTS: Among 76 participating patients, 38 were randomized to the losartan and the placebo group, respectively. The incidence rates of hyperenzymemia and acute pancreatitis among all 76 participating patients were 21% and 12%, respectively. Hyperenzymemia was detected in 9 and 7 patients in the losartan and placebo group, respectively. There were no major differences between the comparison groups regarding cannulation difficulty, findings, or proportion of patients requiring drainage of the bile ducts. There were, however, more pancreatic duct injections, a greater extent of pancreatography, and more biliary sphincterotomies in the losartan group than in the placebo group. Losartan was not associated with risk of hyperenzymemia compared to the placebo group after multi-varible logistic regression analysis (odds ratio 1.6, 95%CI 0.3-7.8). CONCLUSION: In this randomized trial 50 mg losartan given orally had no prophylactic effect on development of hyperenzymemia after ERCP.展开更多
Metastatic bone disease of the distal extremities,also known as acrometastasis,is very rare.Thus,there is very limited information regarding the clinical manifestations and methods of surgical treatment.The current av...Metastatic bone disease of the distal extremities,also known as acrometastasis,is very rare.Thus,there is very limited information regarding the clinical manifestations and methods of surgical treatment.The current available literature shows that acrometastases are often encountered in the context of advanced disease and are thus associated with poor patient survival.As metastatic bone disease is generally uncurable,the goal of surgical treatment is to provide the patient with good function with as few complications as possible.In this article,we discuss the clinical manifestation of acrometastases,the methods of surgical intervention,and the expected clinical outcome.Non-surgically managed pathological fractures generally remain ununited;therefore,conservative treatment is reserved for patients with poor general condition or dismal prognosis.The current evidence suggests that in lesions of the lower arm and leg,osteosynthesis(plate and screw fixation or intramedullary nail)is the most common method of reconstruction,whereas local excision or amputation are more commonly used in cases of more distal lesions(such as ankle,foot and hand).Following surgery most patients receive adjuvant radiotherapy,even though its role is poorly documented.Close collaboration between orthopedic surgeons and medical oncologists is necessary to improve patient care and treatment outcome.Further studies are needed in order to provide stronger clinical evidence and improve decision-making,in an effort to optimize the patients’quality of life and avoid the need for revision surgery.展开更多
Type 2 diabetes mellitus and Parkinson's disease are chronic diseases linked to a growing pandemic that affects older adults and causes significant socio-economic burden.Epidemiological data supporting a close rel...Type 2 diabetes mellitus and Parkinson's disease are chronic diseases linked to a growing pandemic that affects older adults and causes significant socio-economic burden.Epidemiological data supporting a close relationship between these two aging-related diseases have resulted in the investigation of shared pathophysiological molecular mechanisms.Impaired insulin signaling in the brain has gained increasing attention during the last decade and has been suggested to contribute to the development of Parkinson's disease through the dysregulation of several pathological processes.The contribution of type 2 diabetes mellitus and insulin resistance in neurodegeneration in Parkinson's disease,with emphasis on brain insulin resistance,is extensively discussed in this article and new therapeutic strategies targeting this pathological link are presented and reviewed.展开更多
In a recent article, Gorissen et al report on 795 patients with primary colorectal anastomosis operated on during the period 2008-2010 for different colorectal conditions at two centres. The leakage rate was significa...In a recent article, Gorissen et al report on 795 patients with primary colorectal anastomosis operated on during the period 2008-2010 for different colorectal conditions at two centres. The leakage rate was significantly higher among patients who were administered non-steroidal anti-inflammatory drugs (NSAIDs) in the perioperative course. A dose-response relationship could also be traced, where longer NSAID use yielded a higher risk of anastomotic breakdown. However, as this study is observational in design, confounding by indication may be present and there is also a risk of residual confounding from unmeasured covariates. Moreover, the question whether different affinity for the cyclooxygenase enzyme is important in different NSAIDs seems to be largely unanswered. The results, conclusions and clinical relevance of the aforementioned study, including the possible effects of different types of NSAIDs, are discussed. While acknowledging that this study represents the best attempt so far in establishing the causal relationship between perioperative NSAID use and anastomotic leakage, the need for further research in this important area is underlined.展开更多
Parenteral route of insulin administration has been the mode of treatment for all Type 1 diabetics and Type 2 diabetics with complications.Patient compliance has really been a major concern for this route of administr...Parenteral route of insulin administration has been the mode of treatment for all Type 1 diabetics and Type 2 diabetics with complications.Patient compliance has really been a major concern for this route of administration.Several alternative routes of administration are under consideration for effective glycemic control,including oral,inhaled,buccal,nasal,and patch routes.One of the approaches involving inhaled insulin has now reached the market.Several other candidates may reach the market in the near future,the promising one being oral insulin.展开更多
AIM To assess risk factors of hospital admission for acute colonic diverticulitis.METHODS The study was conducted as part of the second wave of the population-based North Trondelag Health Study(HUNT2), performed in No...AIM To assess risk factors of hospital admission for acute colonic diverticulitis.METHODS The study was conducted as part of the second wave of the population-based North Trondelag Health Study(HUNT2), performed in North Trondelag County, Norway, 1995 to 1997. The study consisted of 42570 participants(65.1% from HUNT2) who were followed up from 1998 to 2012. Of these, 22436(52.7%) were females. The cases were defined as those 358 participants admitted with acute colonic diverticulitis during follow-up. The remaining participants were used as controls. Univariable and multivariable Cox regression analyses was used for each sex separately after multiple imputation to calculate HR.RESULTS Multivariable Cox regression analyses showed that increasing age increased the risk of admission for acute colonic diverticulitis: Comparing with ages < 50 years, females with age 50-70 years had HR = 3.42, P < 0.001 and age > 70 years, HR = 6.19, P < 0.001. In males the corresponding values were HR = 1.85, P = 0.004 and 2.56, P < 0.001. In patients with obesity(body mass index ≥ 30) the HR = 2.06, P < 0.001 in females and HR = 2.58, P < 0.001 in males. In females, present(HR = 2.11, P < 0.001) or previous(HR = 1.65, P = 0.007) cigarette smoking increased the risk of admission. In males, breathlessness(HR = 2.57, P < 0.001) and living in rural areas(HR = 1.74, P = 0.007) increased the risk. Level of education, physical activity, constipation and type of bread eaten showed no association with admission for acute colonic diverticulitis.CONCLUSION The risk of hospital admission for acute colonic diverticulitis increased with increasing age, in obese individuals, in ever cigarette smoking females and in males living in rural areas.展开更多
Real time quantitative PCR (RT-qPCR) requires a method to normalize the expression of target genes against an en- dogenous reference gene. It is known that commonly used housekeeping genes (HKGs) vary tremendously in ...Real time quantitative PCR (RT-qPCR) requires a method to normalize the expression of target genes against an en- dogenous reference gene. It is known that commonly used housekeeping genes (HKGs) vary tremendously in inflam- matory conditions;however information about the stability and expression of HKGs in chronic inflammatory joint dis- ease such as rheumatoid arthritis (RA) is scarce. The expressional stability of 10 commonly used HKGs was analyzed in the neuronal (spinal cord, dorsal root ganglia) and in the musculoskeletal tissues (tendon, muscle, epiphysis, capsule, periosteum and ankle joint) using RT-qPCR in the rat model of RA. In individual tissues, suitable HKGs were selected by | △Ct| (│Ct control-Ct arthritis│) and further analyzed by using software programs;geNorm and normfinder. We found hypoxanthine-guanine phosphoribosyl tranferase (HPRT) as the most stable gene except ankle joint while glyce-raldehyde-3-phosphate dehydrogenase (GAPDH) was found as the least stable gene in musculoskeletal tissues. In in-flamed ankle joint where no reference gene was found to be stably expressed, an inflammatory cell marker CD3 was used to normalize peptidylprolyl isomerase B (PPIB), the most homogenous HKG identified among the 10 HKGs. The normalized PPIB was then used to analyze the gene expression of neurokinin 1 (NK1), receptor of substance P, a potent pro-inflammatory mediator. We observed a 3.5 fold increase (p = 0.009) in NK1 expression in inflamed ankle joint compared to control. Our results indicate that reference genes stability should be evaluated before using them as refer- ence during inflammatory conditions. In tissues with intense inflammatory cell infiltration, an inflammatory cell marker should be used to normalize the selected reference gene to avoid erroneous results.展开更多
1 Cardiovascular disease and temperature Cardiovascular disease(CVD)is the leading cause of global mortality and morbidity[1].The intricate relationships between environmental,lifestyle and genetic factors and their r...1 Cardiovascular disease and temperature Cardiovascular disease(CVD)is the leading cause of global mortality and morbidity[1].The intricate relationships between environmental,lifestyle and genetic factors and their respective and collective involvements in the risk development of CVD poses a colossal challenge to decreasing global burdens[2-3].Despite difficulties in pinpointing underlying causes for exacerbating CVD,multiple studies have clearly illuminated the impact that climate and temperature,especially cold weather[4-5]and the winter season[6-7],impose on the incidence of cardiovascular events.The irrefutable association between low temperatures and increased prevalence of myocardial infarction events[8-9]is common to both in Northern and Southern hemispheres[10],as well as to countries at various stages of economic development[11].展开更多
This case report describe severe osteonecrosis of the pelvis more than 30 years after radiation due to ovarian cancer. As orthopedic surgeon it is important to ask about previous radiation to the pelvis in case of tot...This case report describe severe osteonecrosis of the pelvis more than 30 years after radiation due to ovarian cancer. As orthopedic surgeon it is important to ask about previous radiation to the pelvis in case of total hip arthroplasty and also to perform CT in unclear cases.展开更多
BACKGROUND Zinc is a key element in numerous proteins and plays an important role in essential cell functions such as defense against free radicals and DNA damage repair. Chronic pancreatitis(CP) is a chronic inflamma...BACKGROUND Zinc is a key element in numerous proteins and plays an important role in essential cell functions such as defense against free radicals and DNA damage repair. Chronic pancreatitis(CP) is a chronic inflammation with progressive fibrosis of pancreas ultimately resulting in pancreatic exocrine insufficiency(PEI),which is associated with malnutrition. Studies analyzing zinc levels in patients with CP are sparse and lead to conflicting results.AIM To investigate serum zinc levels in patients with CP of various etiologies.METHODS Between October 2015 and March 2018, patients with a diagnosis of CP were identified and recruited from the Pancreatic Outpatient Clinic at the Karolinska University Hospital in Stockholm, Sweden. Demographic, clinical and laboratory data were analyzed. Etiology of CP was determined according to the MANNHEIM classification system into the following etiological subcategories:alcohol consumption, nicotine consumption, hereditary factors, efferent pancreatic duct factors and immunological factors. Pancreatic exocrine function was defined as normal(fecal elastase 1 > 200 μg/g), mildly reduced(100-200μg/g) and severely reduced(fecal elastase 1 < 100 μg/g).RESULTS A total of 150 patients were included in the analysis. Zinc deficiency(< 11μmol/L) was present in 39(26.0%) of patients: 22 females and 17 males. In the group of patients with zinc deficiency, 76.7% of patients had an exocrine pancreatic insufficiency(FE-1 < 200 μg/g). Older age was significantly associated with low zinc levels. Following a univariate analysis, patients aged 60-69 and patients ≥ 70 years of age had a significantly higher prevalence of zinc deficiencies compared to patients < 40 years of age [OR: 3.8, 95%CI(1.08-13.4); P= 0.04]; [OR 6.26, 95%CI(1.94-20.2), P > 0.002]. Smoking and number of packyears were additionally associated with low zinc levels. The risk of zinc deficiency in current smokers and smokers with ≥ 20 pack-years was approximately three times higher compared to those who had never smoked.Gender, body mass index, etiology of CP, presence of diabetes mellitus, levels of glycated hemoglobin(HbA1 c), bone mineral density, alcohol intake and presence of PEI were not associated with low zinc levels.CONCLUSION Zinc deficiency is common in patients with CP and is significantly associated with age ≥ 60, smoking and the number of pack-years, but not with PEI.展开更多
Mast cells are emerging as players in the communication between peripheral nerve endings and cells of the immune system.However,it is not clear the mechanism by which mast cells communicate with peripheral nerves.We p...Mast cells are emerging as players in the communication between peripheral nerve endings and cells of the immune system.However,it is not clear the mechanism by which mast cells communicate with peripheral nerves.We previously found that mast cells located within healing tendons can express glutamate receptors,raising the possibility that mast cells may be sensitive to glutamate signaling.To evaluate this hypothesis,we stimulated primary mast cells with glutamate and showed that glutamate induced the profound upregulation of a panel of glutamate receptors of both the ionotropic type(NMDAR1,NMDAR2A,and NMDAR2B)and the metabotropic type(mGluR2 and mGluR7)at both the mRNA and protein levels.The binding of glutamate to glutamate receptors on the mast cell surface was confirmed.Further,glutamate had extensive effects on gene expression in the mast cells,including the upregulation of proinflammatory components such as IL-6 and CCL2.Glutamate also induced the upregulation of transcription factors,including Egr2,Egr3 and,in particular,FosB.The extensive induction of FosB was confirmed by immunofluorescence assessment.Glutamate receptor antagonists abrogated the responses of the mast cells to glutamate,supporting the supposition of a functional glutamate–glutamate receptor axis in mast cells.Finally,we provide in vivo evidence supporting a functional glutamate–glutamate receptor axis in the mast cells of injured tendons.Together,these findings establish glutamate as an effector of mast cell function,thereby introducing a novel principle for how cells in the immune system can communicate with nerve cells.展开更多
文摘Cell-cell fusion is a normal biological process playing essential roles in organ formation and tissue differentiation,repair and regeneration.Through cell fusion somatic cells undergo rapid nuclear reprogramming and epigenetic modifications to form hybrid cells with new genetic and phenotypic properties at a rate exceeding that achievable by random mutations.Factors that stimulate cell fusion are inflammation and hypoxia.Fusion of cancer cells with non-neoplastic cells facilitates several malignancy-related cell phenotypes,e.g.,reprogramming of somatic cell into induced pluripotent stem cells and epithelial to mesenchymal transition.There is now considerable in vitro,in vivo and clinical evidence that fusion of cancer cells with motile leucocytes such as macrophages plays a major role in cancer metastasis.Of the many changes in cancer cells after hybridizing with leucocytes,it is notable that hybrids acquire resistance to chemo-and radiation therapy.One phenomenon that has been largely overlooked yet plays a role in these processes is polyploidization.Regardless of the mechanism of polyploid cell formation,it happens in response to genotoxic stresses and enhances a cancer cell’s ability to survive.Here we summarize the recent progress in research of cell fusion and with a focus on an important role for polyploid cells in cancer metastasis.In addition,we discuss the clinical evidence and the importance of cell fusion and polyploidization in solid tumors.
基金Pfizer, SwedenStockholm County Council (ALF-grants).
文摘Background: Pituitary insufficiencies after traumatic brain injury (TBI) and subarachnoid haem-orrhage (SAH) have been reported with very varying frequencies. The aim of this study was to describe the pituitary function in the acute phase after TBI and SAH in a cohort of adults and relate the results to injury variables. Methods: Adults admitted to the neurointensive care unit in our hospital after moderate and severe TBI or SAH were included prospectively. Demographic, clinical, laboratory, including ACTH stimulation test, and radiological data were collected. Results: A total of 130 adults, 84 (19 women/65 men) with TBI and 46 (38 women/8 men) with SAH were included. Nine patients with TBI and six patients with SAH responded insufficiently to ACTH stimulation;14 patients with TBI and 9 patients with SAH had low fT4 and low-normal TSH levels. No relations were seen between hormonal levels and injury variables. Conclusions: Pituitary deficiencies occur after TBI and SAH, and a continuous endocrine evaluation of these patients is important. Our study could not define a marker for increased risk for pituitary deficiency. The long-term clinical outcome of the pathological hormone levels in the early phase after TBI and SAH is not known in detail and further studies to elucidate this are needed.
文摘Previous published studies have shown an improvement of penile hemodynamic parameters after low-intensity extracorporeal shockwave therapy(Li-ESWT).However,the clinical significance of these findings remains unclear,and definitive selection criteria for Li-ESWT based on preexisting comorbidities have yet to be established.This was an observational study of 113 patients with ED,evaluated between January 2019 and December 2021 in Andrology Unit at the Department of Urology and Renal Transplantation,University of Foggia(Foggia,Italy).Penile dynamic Doppler was performed to evaluate vascular parameters and 5-item version of the International Index of Erectile Dysfunction(IIEF-5)questionnaire was administered to assess the severity of ED.This was repeated 1 month after treatment.Patients with a peak systolic velocity(PSV)<30 cm s−1 were considered eligible for Li-ESWT.Our protocol consisted of 8 weekly sessions with 1500 strokes distributed in 5 different locations along the penis.After treatment,a significant mean(±standard deviation[s.d.])PSV increase of 5.0(±3.4)cm s−1 was recorded and 52/113(46.0%)patients reached a PSV>30 cm s−1 at posttherapeutic penile dynamic Doppler.A clinically significant IIEF-5 score improvement was observed in 7 patients,21 patients,and 2 patients with mild-to-moderate,moderate,and severe pretreatment ED,respectively.No different outcomes were assessed based on smoking habits,previous pelvic surgery,or use of oral phosphodiesterase-5 inhibitor(PDE5i).On the other side,only 1(6.7%)in 15 patients with diabetes mellitus showed an IIEF-5 score improvement after Li-ESWT.Shockwave treatment determined a significant increase in PSV and correlated IIEF-5 improvement in ED patients.This advantage seemed particularly evident for moderate ED and was not affected by smoking habits,previous pelvic surgery,and use of PDE5i.Conversely,diabetic patients did not benefit from the treatment.
基金Supported by The Swedish Research CouncilThe Swedish Cancer SocietyThe Cancer Society in Stockholm
文摘AIM: To clarify the association between physical activity and gastroesophageal reflux disease (GERD) in nonobese and obese people. METHODS: A Swedish population-based cross-sectional survey was conducted. Participants aged 40-79 years were randomly selected from the Swedish Registry of the Total Population. Data on physical activity, GERD, body mass index (BMI) and the covariates age, gender, comorbidity, education, sleeping problems, and tobacco smoking were obtained using validated questionnaires. GERD was self-reported and defined as heartburn or regurgitation at least once weekly, and having at least moderate problems from such symptoms. Frequency of physical activity was categorized into three groups: (1) "high" (several times/week); (2) "intermediate" (approximately once weekly); and (3) "low" (1-3 times/mo or less). Analyses were stratified for participants with "normal weight" (BMI < 25 kg/m 2 ), "overweight" (BMI 25 to ≤ 30 kg/m 2 ) and "obese" (BMI > 30 kg/m 2 ). Multivariate logistic regression was used to calculate odds ratios (ORs) with 95% confidence intervals (CIs), adjusted for potential confounding by covariates. RESULTS: Of 6969 eligible and randomly selected individuals, 4910 (70.5%) participated. High frequency of physical activity was reported by 2463 (50%) participants, GERD was identified in 472 (10%) participants, and obesity was found in 680 (14%). There were 226 (5%) individuals with missing information about BMI. Normal weight, overweight and obese participants were similar regarding distribution of gender and tobacco smoking status, while obese participants were on average slightly older, had fewer years of education, more comorbidity, slightly more sleeping problems, lower frequency of physical activity, and higher occurrence of GERD. Among the 2146 normal-weight participants, crude point estimates indicated a decreased risk of GERD among individuals with high frequency of physical activity (OR: 0.59, 95% CI: 0.39-0.89), compared to low frequency of physical activity. However, after adjustment for potential confounding factors, neither intermediate (OR: 1.30, 95% CI: 0.75-2.26) nor high (OR: 0.99, 95% CI: 0.62-1.60) frequency of physical activity was followed by decreased risk of GERD. Sleeping problems and high comorbidity were identified as potential confounders. Among the 1859 overweight participants, crude point estimates indicated no increased or decreased risk of GERD among individuals with intermediate or high frequency of physical activity, compared to low frequency. After adjustment for confounding, neither intermediate (OR: 0.75, 95% CI: 0.46-1.22) nor high frequency of physical activity were followed by increased or decreased risk of GERD compared to low frequency among nonobese participants. Sleeping problems and high comorbidity were identified as potential confounders for overweight participants. In obese individuals, crude ORs were similar to the adjusted ORs and no particular confounding factors were identified. Intermediate frequency of physical activity was associated with a decreased occurrence of GERD compared to low frequency of physical activity (adjusted OR: 0.41, 95% CI: 0.22-0.77). CONCLUSION: Intermediate frequency of physical activity might decrease the risk of GERD among obese individuals, while no influence of physical activity on GERD was found in non-obese people.
文摘Repeated surveys from Europe, the United States, Australia, and New Zealand have shown that adherence to an evidence-based perioperative care protocol, such as Enhanced Recovery After Surgery(ERAS), has been generally low. It is of great importance to support the implementation of the ERAS protocol as it has been shown to improve outcomes after a number of surgical procedures, including major abdominal surgery. However, despite an increasing awareness of the importance of structured perioperative management, the implementation of this complex protocol has been slow. Barriers to implementation involve both patient- and staff-related factors as well as practice-related issues and resources. To support efficient and successful implementation, further educational and structural measures have to be made on a national or regional level to improve the standard of general health care. Besides postoperative morbidity, biological and physiological variables have been quite commonly reported in previous ERAS studies. Little information, however, has been obtained on cost-effectiveness, long-term outcomes, quality of life and patient-related outcomes, and these issues remain important areas of research for future studies.
文摘AIM To systematically review the literature on women with both diabetes in pregnancy(DIP) and depression during or after pregnancy. METHODS In this systematic literature review, PubM ed/MEDLINE and EMBASE were searched(13 November 2015) using terms for diabetes(type 1, type 2, or gestational), depression, and pregnancy(no language or date restrictions). Publications that reported on women who had both DIP(any type) and depression or depressive symptoms before, during, or within one year after pregnancy were considered for inclusion. All study types were eligible for inclusion; conference abstracts, narrative reviews, nonclinical letters, editorials, and commentaries were excluded, unless they provided treatment guidance.RESULTS Of 1189 articles identified, 48 articles describing women with both DIP and depression were included(sample sizes 36 to > 32 million). Overall study quality was poor; most studies were observational, and only 12 studies(mostly retrospective database studies) required clinical depression diagnosis. The prevalence of concurrent DIP(any type) and depression in general populations of pregnant women ranged from 0% to 1.6%(median 0.61%; 12 studies). The prevalence of depression among women with gestational diabetes ranged from 4.1% to 80%(median 14.7%; 16 studies). Many studies examined whether DIP was a risk factor for depression or depression was a risk factor for DIP. However, there was no clear consensus for either relationship. Importantly, we found limited guidance on the management of women with both DIP and depression. CONCLUSION Given the increasing prevalence of diabetes and depression, high-quality research and specific guidance for management of pregnant women with both conditions are warranted.
文摘BACKGROUNDDiabetes mellitus causes a large majority of non-traumatic major and minoramputations globally. Patients with diabetes are clinically complex with amultifactorial association between diabetic foot ulcers (DFU) and subsequentlower extremity amputations (LEA). Few studies show the long-term outcomeswithin the cohort of DFU-associated LEA.AIMTo highlight the long-term outcomes of LEA as a result of DFU.METHODSPubMed/MEDLINE and Google Scholar were searched for key terms, “diabetes”,“foot ulcers”, “amputations” and “outcomes”. Outcomes such as mortality, reamputation,re-ulceration and functional impact were recorded. Peer-reviewedstudies with adult patients who had DFU, subsequent amputation and follow upof at least 1 year were included. Non-English language articles or studiesinvolving children were excluded.RESULTSA total of 22 publications with a total of 2334 patients were selected against theinclusion criteria for review. The weighted mean of re-amputation was 20.14%,29.63% and 45.72% at 1, 3 and 5 years respectively. The weighted mean of mortality at 1, 3 and 5 years were 13.62%, 30.25% and 50.55% respectively withsignificantly higher rates associated with major amputation, re-amputation andischemic cardiomyopathy.CONCLUSIONPrevious LEA, level of the LEA and patient comorbidities were significant riskfactors contributing to re-ulceration, re-amputation, mortality and depreciatedfunctional status.
基金Supported by Magn Bergvalls Foundation,Karolinska Institutet and Stockholm County Council
文摘AIM: To perform a systematic review of reported neonatal and pregnancy outcomes of Indigenous Australians with diabetes in pregnancy(DIP).METHODS: Electronic searches of Pub Med and Web of Science were carried out. Articles were selected if they contained original data on DIP outcomes in Indigenous Australians. There were no specific exclusion criteria.RESULTS: A total of eight articles, predominantly from Queensland and Western Australia were identified once inclusion criteria were applied. Birth data from midwifery registries or paper charts encompassing years 1985-2008 were used. A total of 465591 pregnant women with and without DIP were included in the eight studies, with 1363 being Indigenous women with DIP. Indigenous Australians experienced increased rates of many known adverse outcomes of DIP including: macrosomia, caesarean section, congenital deformities, low birth weight, hypoglycaemia, and neonatal trauma. There were regional differences among Indigenous Australians, particularly regional/remote vs metropolitan populations where the regional/remote data showed worse outcomes. Two of the articles did not note a difference between Aboriginals and Caucasians in the rates of measured adverse outcome. Studies varied significantly in size, measured outcomes, and subsequent analysis.CONCLUSION: The health disparities between Indigenous Australians and non-Indigenous Australians are further evidenced by poorer outcomes in DIP. This has broader implications for Indigenous health in general.
文摘Standard treatment for soft tissue sarcoma,based on complete surgical resection with or without adjuvant radiotherapy and chemotherapy,has not substantially changed during the last several decades.Nevertheless,recent advances have contributed to considerable improvement in the management of these patients;for example,new magnetic resonance imaging sequences such as diffusionweighted imaging and magnetic resonance imaging radiomics can better assess tumor extension and even estimate its grade.Detection of circulating genetic material(liquid biopsy)and next-generation sequencing are powerful techniques for genetic analysis,which will increase our understanding of the underlying molecular mechanisms and may reveal potential therapeutic targets.The role of chemotherapy in non-metastatic disease is still controversial,and there is a need to identify patients who really benefit from this treatment.Novel chemotherapeutic regimens have entered clinical praxis and can change the outcome of patients with metastatic disease.Advances in radiotherapy have helped decrease local adverse effects and sustain good local control of the disease.The following report provides an updated view of the diagnosis,treatment,and future perspectives on the management of patients with soft tissue sarcomas.
基金Supported by The Swedish Society of Medicine, The Lisa and Johan Grnberg Foundation
文摘AIM: To study if the angiotensin II receptor blockers (ARB) losartan counteracts pancreatic hyperenzymemia as measured 24 h after endoscopic retrograde cholangiopancreatography (ERCP). METHODS: A triple-blind and placebo-controlled randomized clinical trial was performed at two Swedish hospitals in 2006-2008. Patients over 18 years of age undergoing ERCP, excluding those with current pancreatitis, current use of ARB, and severe disease, such as sepsis, liver and renal failure. One oral dose of 50 mg losartan or placebo was given one hour before ERCP. The relative risk of hyperenzymemia 24 h after ERCP was estimated using multivariable logistic regression, and expressed as odds ratio with 95% confidence intervals (CIs), including adjustment for potential remaining confounding. RESULTS: Among 76 participating patients, 38 were randomized to the losartan and the placebo group, respectively. The incidence rates of hyperenzymemia and acute pancreatitis among all 76 participating patients were 21% and 12%, respectively. Hyperenzymemia was detected in 9 and 7 patients in the losartan and placebo group, respectively. There were no major differences between the comparison groups regarding cannulation difficulty, findings, or proportion of patients requiring drainage of the bile ducts. There were, however, more pancreatic duct injections, a greater extent of pancreatography, and more biliary sphincterotomies in the losartan group than in the placebo group. Losartan was not associated with risk of hyperenzymemia compared to the placebo group after multi-varible logistic regression analysis (odds ratio 1.6, 95%CI 0.3-7.8). CONCLUSION: In this randomized trial 50 mg losartan given orally had no prophylactic effect on development of hyperenzymemia after ERCP.
文摘Metastatic bone disease of the distal extremities,also known as acrometastasis,is very rare.Thus,there is very limited information regarding the clinical manifestations and methods of surgical treatment.The current available literature shows that acrometastases are often encountered in the context of advanced disease and are thus associated with poor patient survival.As metastatic bone disease is generally uncurable,the goal of surgical treatment is to provide the patient with good function with as few complications as possible.In this article,we discuss the clinical manifestation of acrometastases,the methods of surgical intervention,and the expected clinical outcome.Non-surgically managed pathological fractures generally remain ununited;therefore,conservative treatment is reserved for patients with poor general condition or dismal prognosis.The current evidence suggests that in lesions of the lower arm and leg,osteosynthesis(plate and screw fixation or intramedullary nail)is the most common method of reconstruction,whereas local excision or amputation are more commonly used in cases of more distal lesions(such as ankle,foot and hand).Following surgery most patients receive adjuvant radiotherapy,even though its role is poorly documented.Close collaboration between orthopedic surgeons and medical oncologists is necessary to improve patient care and treatment outcome.Further studies are needed in order to provide stronger clinical evidence and improve decision-making,in an effort to optimize the patients’quality of life and avoid the need for revision surgery.
基金support from Region Stockholm,ALF-project(FoUI-960041)Open Access funding is provided by Karolinska Institute(both to IM)。
文摘Type 2 diabetes mellitus and Parkinson's disease are chronic diseases linked to a growing pandemic that affects older adults and causes significant socio-economic burden.Epidemiological data supporting a close relationship between these two aging-related diseases have resulted in the investigation of shared pathophysiological molecular mechanisms.Impaired insulin signaling in the brain has gained increasing attention during the last decade and has been suggested to contribute to the development of Parkinson's disease through the dysregulation of several pathological processes.The contribution of type 2 diabetes mellitus and insulin resistance in neurodegeneration in Parkinson's disease,with emphasis on brain insulin resistance,is extensively discussed in this article and new therapeutic strategies targeting this pathological link are presented and reviewed.
文摘In a recent article, Gorissen et al report on 795 patients with primary colorectal anastomosis operated on during the period 2008-2010 for different colorectal conditions at two centres. The leakage rate was significantly higher among patients who were administered non-steroidal anti-inflammatory drugs (NSAIDs) in the perioperative course. A dose-response relationship could also be traced, where longer NSAID use yielded a higher risk of anastomotic breakdown. However, as this study is observational in design, confounding by indication may be present and there is also a risk of residual confounding from unmeasured covariates. Moreover, the question whether different affinity for the cyclooxygenase enzyme is important in different NSAIDs seems to be largely unanswered. The results, conclusions and clinical relevance of the aforementioned study, including the possible effects of different types of NSAIDs, are discussed. While acknowledging that this study represents the best attempt so far in establishing the causal relationship between perioperative NSAID use and anastomotic leakage, the need for further research in this important area is underlined.
基金support from Swedish Medical Research Council,Svenskadiabetes Forbundet,Barndiabetesfonden,Svenskadiabetes StiftelsenKarolinska Institute and Karolinska University Hospital to Carani B.Sanjeevi
文摘Parenteral route of insulin administration has been the mode of treatment for all Type 1 diabetics and Type 2 diabetics with complications.Patient compliance has really been a major concern for this route of administration.Several alternative routes of administration are under consideration for effective glycemic control,including oral,inhaled,buccal,nasal,and patch routes.One of the approaches involving inhaled insulin has now reached the market.Several other candidates may reach the market in the near future,the promising one being oral insulin.
基金Supported by Institute of Cancer Research and Molecular Medicine,The Medical Faculty,Norwegian University of Science and Technology,Trondheim,Norwaythe Department of Research,Levanger Hospital,Levanger
文摘AIM To assess risk factors of hospital admission for acute colonic diverticulitis.METHODS The study was conducted as part of the second wave of the population-based North Trondelag Health Study(HUNT2), performed in North Trondelag County, Norway, 1995 to 1997. The study consisted of 42570 participants(65.1% from HUNT2) who were followed up from 1998 to 2012. Of these, 22436(52.7%) were females. The cases were defined as those 358 participants admitted with acute colonic diverticulitis during follow-up. The remaining participants were used as controls. Univariable and multivariable Cox regression analyses was used for each sex separately after multiple imputation to calculate HR.RESULTS Multivariable Cox regression analyses showed that increasing age increased the risk of admission for acute colonic diverticulitis: Comparing with ages < 50 years, females with age 50-70 years had HR = 3.42, P < 0.001 and age > 70 years, HR = 6.19, P < 0.001. In males the corresponding values were HR = 1.85, P = 0.004 and 2.56, P < 0.001. In patients with obesity(body mass index ≥ 30) the HR = 2.06, P < 0.001 in females and HR = 2.58, P < 0.001 in males. In females, present(HR = 2.11, P < 0.001) or previous(HR = 1.65, P = 0.007) cigarette smoking increased the risk of admission. In males, breathlessness(HR = 2.57, P < 0.001) and living in rural areas(HR = 1.74, P = 0.007) increased the risk. Level of education, physical activity, constipation and type of bread eaten showed no association with admission for acute colonic diverticulitis.CONCLUSION The risk of hospital admission for acute colonic diverticulitis increased with increasing age, in obese individuals, in ever cigarette smoking females and in males living in rural areas.
文摘Real time quantitative PCR (RT-qPCR) requires a method to normalize the expression of target genes against an en- dogenous reference gene. It is known that commonly used housekeeping genes (HKGs) vary tremendously in inflam- matory conditions;however information about the stability and expression of HKGs in chronic inflammatory joint dis- ease such as rheumatoid arthritis (RA) is scarce. The expressional stability of 10 commonly used HKGs was analyzed in the neuronal (spinal cord, dorsal root ganglia) and in the musculoskeletal tissues (tendon, muscle, epiphysis, capsule, periosteum and ankle joint) using RT-qPCR in the rat model of RA. In individual tissues, suitable HKGs were selected by | △Ct| (│Ct control-Ct arthritis│) and further analyzed by using software programs;geNorm and normfinder. We found hypoxanthine-guanine phosphoribosyl tranferase (HPRT) as the most stable gene except ankle joint while glyce-raldehyde-3-phosphate dehydrogenase (GAPDH) was found as the least stable gene in musculoskeletal tissues. In in-flamed ankle joint where no reference gene was found to be stably expressed, an inflammatory cell marker CD3 was used to normalize peptidylprolyl isomerase B (PPIB), the most homogenous HKG identified among the 10 HKGs. The normalized PPIB was then used to analyze the gene expression of neurokinin 1 (NK1), receptor of substance P, a potent pro-inflammatory mediator. We observed a 3.5 fold increase (p = 0.009) in NK1 expression in inflamed ankle joint compared to control. Our results indicate that reference genes stability should be evaluated before using them as refer- ence during inflammatory conditions. In tissues with intense inflammatory cell infiltration, an inflammatory cell marker should be used to normalize the selected reference gene to avoid erroneous results.
文摘1 Cardiovascular disease and temperature Cardiovascular disease(CVD)is the leading cause of global mortality and morbidity[1].The intricate relationships between environmental,lifestyle and genetic factors and their respective and collective involvements in the risk development of CVD poses a colossal challenge to decreasing global burdens[2-3].Despite difficulties in pinpointing underlying causes for exacerbating CVD,multiple studies have clearly illuminated the impact that climate and temperature,especially cold weather[4-5]and the winter season[6-7],impose on the incidence of cardiovascular events.The irrefutable association between low temperatures and increased prevalence of myocardial infarction events[8-9]is common to both in Northern and Southern hemispheres[10],as well as to countries at various stages of economic development[11].
文摘This case report describe severe osteonecrosis of the pelvis more than 30 years after radiation due to ovarian cancer. As orthopedic surgeon it is important to ask about previous radiation to the pelvis in case of total hip arthroplasty and also to perform CT in unclear cases.
文摘BACKGROUND Zinc is a key element in numerous proteins and plays an important role in essential cell functions such as defense against free radicals and DNA damage repair. Chronic pancreatitis(CP) is a chronic inflammation with progressive fibrosis of pancreas ultimately resulting in pancreatic exocrine insufficiency(PEI),which is associated with malnutrition. Studies analyzing zinc levels in patients with CP are sparse and lead to conflicting results.AIM To investigate serum zinc levels in patients with CP of various etiologies.METHODS Between October 2015 and March 2018, patients with a diagnosis of CP were identified and recruited from the Pancreatic Outpatient Clinic at the Karolinska University Hospital in Stockholm, Sweden. Demographic, clinical and laboratory data were analyzed. Etiology of CP was determined according to the MANNHEIM classification system into the following etiological subcategories:alcohol consumption, nicotine consumption, hereditary factors, efferent pancreatic duct factors and immunological factors. Pancreatic exocrine function was defined as normal(fecal elastase 1 > 200 μg/g), mildly reduced(100-200μg/g) and severely reduced(fecal elastase 1 < 100 μg/g).RESULTS A total of 150 patients were included in the analysis. Zinc deficiency(< 11μmol/L) was present in 39(26.0%) of patients: 22 females and 17 males. In the group of patients with zinc deficiency, 76.7% of patients had an exocrine pancreatic insufficiency(FE-1 < 200 μg/g). Older age was significantly associated with low zinc levels. Following a univariate analysis, patients aged 60-69 and patients ≥ 70 years of age had a significantly higher prevalence of zinc deficiencies compared to patients < 40 years of age [OR: 3.8, 95%CI(1.08-13.4); P= 0.04]; [OR 6.26, 95%CI(1.94-20.2), P > 0.002]. Smoking and number of packyears were additionally associated with low zinc levels. The risk of zinc deficiency in current smokers and smokers with ≥ 20 pack-years was approximately three times higher compared to those who had never smoked.Gender, body mass index, etiology of CP, presence of diabetes mellitus, levels of glycated hemoglobin(HbA1 c), bone mineral density, alcohol intake and presence of PEI were not associated with low zinc levels.CONCLUSION Zinc deficiency is common in patients with CP and is significantly associated with age ≥ 60, smoking and the number of pack-years, but not with PEI.
基金This study was funded by grants from AFA Forsakring(M.P.).
文摘Mast cells are emerging as players in the communication between peripheral nerve endings and cells of the immune system.However,it is not clear the mechanism by which mast cells communicate with peripheral nerves.We previously found that mast cells located within healing tendons can express glutamate receptors,raising the possibility that mast cells may be sensitive to glutamate signaling.To evaluate this hypothesis,we stimulated primary mast cells with glutamate and showed that glutamate induced the profound upregulation of a panel of glutamate receptors of both the ionotropic type(NMDAR1,NMDAR2A,and NMDAR2B)and the metabotropic type(mGluR2 and mGluR7)at both the mRNA and protein levels.The binding of glutamate to glutamate receptors on the mast cell surface was confirmed.Further,glutamate had extensive effects on gene expression in the mast cells,including the upregulation of proinflammatory components such as IL-6 and CCL2.Glutamate also induced the upregulation of transcription factors,including Egr2,Egr3 and,in particular,FosB.The extensive induction of FosB was confirmed by immunofluorescence assessment.Glutamate receptor antagonists abrogated the responses of the mast cells to glutamate,supporting the supposition of a functional glutamate–glutamate receptor axis in mast cells.Finally,we provide in vivo evidence supporting a functional glutamate–glutamate receptor axis in the mast cells of injured tendons.Together,these findings establish glutamate as an effector of mast cell function,thereby introducing a novel principle for how cells in the immune system can communicate with nerve cells.
