Background: The physiological and biochemical demands of intense exercise elicit both muscle-based and systemic responses. The main adaptations to endurance exercise include the correction of electrolyte imbalance, a ...Background: The physiological and biochemical demands of intense exercise elicit both muscle-based and systemic responses. The main adaptations to endurance exercise include the correction of electrolyte imbalance, a decrease in glycogen storage and the increase of oxidative stress, intestinal permeability, muscle damage, and systemic inflammatory response. Adaptations to exercise might be influenced by the gut microbiota, which plays an important role in the production, storage, and expenditure of energy obtained from the diet as well as in inflammation,redox reactions, and hydration status.Methods: A systematic and comprehensive search of electronic databases, including MEDLINE, Scopus, Clinical Trials.gov, Science Direct,Springer Link, and EMBASE was done. The search process was completed using the keywords: "endurance", "exercise", "immune response","microbiota", "nutrition", and "probiotics".Results: Reviewed literature supports the hypothesis that intestinal microbiota might be able to provide a measureable, effective marker of an athlete's immune function and that microbial composition analysis might also be sensitive enough to detect exercise-induced stress and metabolic disorders. The review also supports the hypothesis that modifying the microbiota through the use of probiotics could be an important therapeutic tool to improve athletes' overall general health, performance, and energy availability while controlling inflammation and redox levels.Conclusion: The present review provides a comprehensive overview of how gut microbiota may have a key role in controlling the oxidative stress and inflammatory responses as well as improving metabolism and energy expenditure during intense exercise.展开更多
Introduction In their article entitled‘Investigating genetic causal relationships between blood pressure and anxiety,depressive symptoms,neuroticism and subjective well-being’,Cai and colleagues1 presented the resul...Introduction In their article entitled‘Investigating genetic causal relationships between blood pressure and anxiety,depressive symptoms,neuroticism and subjective well-being’,Cai and colleagues1 presented the results of a two-sample Mendelian randomisation2(MR)study examining associations between blood pressure traits(systolic,diastolic,hypertension and pulse pressure)and psychological traits(anxiety,depression,neuroticism and subjective well-being).After correction for multiple testing.展开更多
Theoretically, mesenchymal stem cells (MSCs) are very promising as adjuvanttherapy to alleviate coronavirus disease 2019 (COVID-19)-associated acute lunginjury and cytokine storm. Several published studies, which used...Theoretically, mesenchymal stem cells (MSCs) are very promising as adjuvanttherapy to alleviate coronavirus disease 2019 (COVID-19)-associated acute lunginjury and cytokine storm. Several published studies, which used MSCs toalleviate COVID-19-associated acute lung injury and cytokine storm, reportedpromising results. However, the evidence came from a case report, case series,and clinical trials with a limited number of participants. Therefore, more studiesare needed to get robust proof of MSC beneficial effects.展开更多
We prospectively compared the safety and efficacy of bipolar transurethral enucleation of the prostate （TUEP） versus 160-W lithium triboride laser （LBO） photoselective vaporization of the prostate （PVP） for trea...We prospectively compared the safety and efficacy of bipolar transurethral enucleation of the prostate （TUEP） versus 160-W lithium triboride laser （LBO） photoselective vaporization of the prostate （PVP） for treating benign prostatic hyperplasia 〉70 ml.展开更多
Salinity is a major stress that adversely affects growth and productivity in plants. There are species that tolerate this stresswithin the genus Atriplex. Four species, A. lampa, A. crenatifolia, A. nummularia and A. ...Salinity is a major stress that adversely affects growth and productivity in plants. There are species that tolerate this stresswithin the genus Atriplex. Four species, A. lampa, A. crenatifolia, A. nummularia and A. argentina were compared for their ionaccumulation and water relations under saline conditions. A greenhouse study was conducted by irrigating the four species with NaCIsolutions at concentrations 0%, 1%, 2% and 4% starting when plants were six months old. Plants were harvested 45 d after startingthe salinity treatments and analyzed for their ion contents. In the four Atriplex species, Na^＋ and Cl^- contents in plants increased, whileCa^2＋ and Mg^2＋ decreased with the increase of salinity in the irrigation solution. The results suggested that A. argentina and A.nummularia were able to maintain a higher leaf relative water content （RWC） at low leaf water potential, which was associated witha greater capacity of osmotic adjustment. A. lampa showed lower ion accumulation and minor osmotic adjustment than the otherspecies. It can be concluded that the accumulation of ions favors the lower osmotic potential and contributes to osmotic adjustment inthese halophytes.展开更多
The ratio of the second-to-fourth digit length（2D：4D）has been shown to be sexually dimorphic,with males having lower mean than females and the ratio relates to masculinity and femininity in adults.2D：4D is influen...The ratio of the second-to-fourth digit length（2D：4D）has been shown to be sexually dimorphic,with males having lower mean than females and the ratio relates to masculinity and femininity in adults.2D：4D is influenced by digit growth pattern which is related to the ratio of prenatal androgen to estrogen levels in the later part of the first trimester.展开更多
Objective: We employed a multidisciplinary approach incorporating theoretical ideas, clinical experience,psychology, physiology, traditional Chinese medicine(CM), modern practice of CM, and oncology to explore the eff...Objective: We employed a multidisciplinary approach incorporating theoretical ideas, clinical experience,psychology, physiology, traditional Chinese medicine(CM), modern practice of CM, and oncology to explore the effect of patients’ repression of negative emotions and traumatic events on breast cancer(BC) pathogenesis.Methods: BC female patients, older than 18 years of age, with available pathology reports who were treated at Rabin Medical Center were recruited. All participants completed questionnaires regarding medical history, behavioral tendencies, negative emotions, trauma, symptoms, and pathology(from a CM perspective). Data on tumor characteristics were collected from the pathology reports. The associations were examined using hierarchical binary logistic regressions.Results: A total of 155 BC patients were enrolled. The median age was 52 years, with a range of 26–79;95% were mothers;28% had estrogen receptor(ER)-negative BC, 52% had progesterone receptor(PR)-negative BC, 48% had human epidermal growth factor receptor 2-negative BC, and antigen Ki-67 ≥ 20%was reported for 52% of tumors. Statistically significant associations were found between the emotional markers(sense of motherhood failure, and lack of self-fulfillment), avoidance behavior, and physical symptoms that are related to emotional repression based on CM. Significant associations were also found between variables associated with physical symptoms of emotional repression, which involves the production and accumulation of non-substantial phlegm(i.e., ‘‘high-lipid Qi-like microscopic phlegm"),avoidance behavior which unconsciously uses ‘‘high-lipid Qi-like microscopic phlegm" in order to achieve emotional repression, and tumor parameters including tumor grade, PR status, and Ki-67.Patients with higher levels of ‘‘high-lipid Qi-like microscopic phlegm" were more likely to have tumors with worse prognosis(PR-negative, higher grade, and higher Ki-67).Conclusion: We demonstrated a relationship between emotional parameters, behavioral tendencies, CM parameters, and oncologic parameters in BC. Additional research is warranted to explore these associations and their relevance to clinical practice.展开更多
<strong>Background:</strong> In an age of antiretroviral therapy, the life expectancy of children perinatally infected with Human Immunodeficiency Virus (HIV) has significantly increased. At the same time,...<strong>Background:</strong> In an age of antiretroviral therapy, the life expectancy of children perinatally infected with Human Immunodeficiency Virus (HIV) has significantly increased. At the same time, however, pulmonary pathologies secondary to opportunistic infections have decreased thanks to increased diagnostics and access to antiretroviral therapy (ART). Despite this, in these children an immune dysregulation is maintained due to chronic infection. There is evidence that these patients have increased probability of presenting with abnormalities in pulmonary function, mainly with chronic obstructive clinical pictures (25% - 40% of perinatally infected adolescents display some anomaly in the spirometry), which predisposes them to increased risk of chronic pulmonary disease. Since lung development occurs mainly during infancy, patients perinatally infected with HIV may suffer consequences. This can be secondary to opportunistic infections, chronic inflammation due to the virus, and immunologic effects of ART, mainly in non-industrialized countries, where late diagnosis is frequent. <strong>Methodology:</strong> An analytical, observational, cross-sectional study was conducted at Roosevelt Hospital Pediatric infectious disease clinic, from January to December 2019. A sample of 76 patients was obtained, out of a population of 362 patients. A total of 62 subjects, who met the criterion of reproducibility in the spirometry, were analyzed. Results were analyzed with percentages and the association of variables using the chi-squared test (<em>χ</em><sup>2</sup>). <strong>Results:</strong> A decrease in pulmonary function was found in 34% of patients, mild obstructive pattern (16%) predominating. Significant association between basal viral load greater than 100,000 cp/ml and a decrease in Forced expiratory flow 25 - 75 (FEF 25-75) (<em>p</em> 0.046) and in relationship between forced expiratory volume and forced vital capacity (FEV1/ FVC <em>p</em> = 0.024) was observed, as well as a non-statistically significant relationship between advanced clinical stage at diagnosis and decreased pulmonary function. <strong>Conclusions:</strong> The prevalence of decreased pulmonary function related to advanced clinical stage and elevated basal viral load (>100,000 cps/ml) is higher than that reported in other studies (25%) and has an influence in the long-term decrease in pulmonary function.展开更多
Stem cells have moved from lab to bedside, and many initial studies showed promising results. Therefore big companies are entering the business. However, most initial studies did not used controls to make sure of the ...Stem cells have moved from lab to bedside, and many initial studies showed promising results. Therefore big companies are entering the business. However, most initial studies did not used controls to make sure of the efficacy of stem cells. Many phase-1 studies showed safety of stem cell therapies, when precaution measures were adapted. However, efficacy needs to be proven by randomized controlled trials (RCT) to exclude placebo effects. Recently, various RCTs for various conditions have been done with various contradictory results. Therefore, a meta-analysis is very useful to know whether a stem cell therapy really work for a certain condition. As various centres used various type of stem cells, various dose, and route of application, as well as different outcome measures with various results for one certain condition, sometimes it is difficult to conduct a meta-analysis when there is high heterogeneity, which is like pooling “apples” with “oranges” and “avocado” that will lead to a misleading conclusion. In many cases, where the studies are highly heterogeneous, and the heterogeneity can’t be identified, then a descriptive systematic review is the best solution to take a conclusion which protocol is the best and valuable to be standardized. Formerly it was believed that stem cells that are given to patients work by differentiating into the needed cells, and thus replacing damaged cell. However, recent evidence showed that only a few stem cells homed to the desired area, while a large amount went to various areas that were remote from the damaged area. Even though they were trapped in remote areas, the stem cells still exerted beneficial effects by remote signalling and secretion of various beneficial factors. Therefore, there are attempts to produce stem cell secretomes/metabolites to replace the stem cells, as metabolites are easier to handle and transported compared to the cells themselves. In addition, various studies worked on substitute tissue/organs “ex vivo” to be transplanted to replace a damaged organ. There are various means to produce a tissue/an organ/organoid “ex vivo” (tissue engineering) by using various stem cells, scaffold, and soluble factors, in various vessels from static vessel to bioreactors, and “on chips”. Though these attempts are in the initial stage, but some translational animal studies have been done. A more usual use of these “ex vivo” developed tissues/organs/organoids is for drug testing, such as toxicity testing, and for studying the mechanism of certain diseases that is directed toward the development of a cure of the diseases. In conclusion, many stem cell therapies have entered RCTs, but no standardized and approved protocol has been established, while organoids are usually used for drug testing and studying the mechanism of certain diseases.展开更多
Over the past two decades, the neurobiological substrates of the reinforcement theory have been discussed in terms of a behavioral activation system (BAS) and a behavioral inhibition system (BIS). While the BAS has be...Over the past two decades, the neurobiological substrates of the reinforcement theory have been discussed in terms of a behavioral activation system (BAS) and a behavioral inhibition system (BIS). While the BAS has been conceptualized as both an activating system and an approach-related system, the empirical evidence for either approach remains inconclusive. In the current study we hypothesize that the inclusion of self-regulatory capacity contributes to a better understanding of the BAS. In a sample of 29 volunteers motor response inhibition elicited by a stop-signal task and heart rate variability (HRV) as a proxy of self-regulatory capacity were related to BAS scores (BIS/BAS scales [1]). Results show significant positive associations between inhibitory capacity and the sensitivity of the behavioral activation system, suggesting markers of self-regulation as components of the BAS.展开更多
We hypothesize that individuals with genetic predisposition to Substance Use Disorder (SUD) may have greater likelihood of experiencing work related accidents. We further hypothesize that high risk populations will ca...We hypothesize that individuals with genetic predisposition to Substance Use Disorder (SUD) may have greater likelihood of experiencing work related accidents. We further hypothesize that high risk populations will carry single or multiple polymorphisms associated with brain reward circuitry and/or brain reward cascade, including: Dopaminergic (i.e. DRD2 receptor genes);Serotonergic (i.e. 5-HTT2 receptor genes);Endorphinergic (i.e. pre-enkephalin genes);Gabergic (i.e. GABAA receptor genes);Neurotransmitter Metabolizing genes (i.e. MAO and COMT genes) among others (GARSRXTM). Analgesic addiction as well as “pseudoaddiction” must be treated to improve pain control and its management. We propose that non-pharmacological alternatives to pain relief, in high risk, addiction-prone individuals, are Electrotherapeutic Device(s) and Programs. We further propose patented KB220Z, a nutraceutical designed to release dopamine at the nucleus accumbens, will reduce craving behavior, in genetically programmed individuals. By utilizing both alternatives in DNA analyzed injured workers, a reduction in analgesic addiction (genuine or pseudo) leads to improved health and quicker return to work. We also hypothesize that this novel approach will impact costs related to injuries in the workforce. Effective management of chronic pain, especially in high addiction-prone workforce populations, is possible in spite of being particularly elusive. A series of factors encumber pain assessment and management, including analgesia addiction, pharmacogenomic response to pain medications, and genetically inherited factors involving gene polymorphisms. Additional research is required to test these stipulated hypotheses related to genetic proneness to addiction, but also proneness to accidents in the workplace and reduction of craving behavior. Our hypothesis that genotyping coupled with both KB220ZTM and the pharmaceutical-free Electrotherapy, will reduce iatrogenic induced analgesia addiction. This approach will achieve attainable effective pain management and quicker return to work. We propose outcomes such as the Reward Deficiency System SolutionTM may become an adjunct in the war against iatrogenic pain medication addiction.展开更多
The mounting endemic of prescription iatrogenic opioid dependence in pain patients provoked this treatise about an alternative method that can be used to treat pain, improve function and reduce the risk of opioid depe...The mounting endemic of prescription iatrogenic opioid dependence in pain patients provoked this treatise about an alternative method that can be used to treat pain, improve function and reduce the risk of opioid dependence. It is well known that as well as the side effects reported for chronic opioid therapy, genetically predisposed individuals are at risk for opioid dependence. We propose the use of the Genetic Addiction Risk Score (GARS) assessment to identify patients early in treatment who should avoid narcotic pain medications. Primarily, this review will be an exploration of the mechanisms of action of an electrotherapeutic alternative to narcotic treatment that can be used to augment tissue healing and reduce the pain associated with human injuries and neuropathies. This particular electrotherapeutic device was developed at the Electronic Waveform Laboratory in Huntington Beach, California and is called the H-Wave? device. The primary effect of the H-Wave?device is stimulation (HWDS) of small diameter fibers of “red-slow-twitch” skeletal muscle. Mechanisms of action of HWDS have been investigated in both animal and human studies. They include edema reduction, induction of nitric oxide dependent augmented microcirculation and angiogenesis, small muscle contraction that eliminates transcapillary fluid shifts, reducing the painful effects of tetanizing fatigue and gradual loading of healing injured muscle tissue that helps repair and remodeling. A recent metaanalysis found a moderate-to-strong-positive effect of the HWDS in providing pain relief, reducing the requirement for pain medication, with the most robust effect being increased functionality. We are proposing that GARS can be used to identify those at risk of developing opioid dependence and that the need for opioid analgesia can be reduced by use of this electro therapeutic alternative to opioid analgesia in the treatment of pain and injuries.展开更多
Background Psychiatric comorbidities are common in patients with epilepsy.Reasons for the co-occurrence of psychiatric conditions and epilepsy remain poorly understood.Aim We aimed to triangulate the relationship betw...Background Psychiatric comorbidities are common in patients with epilepsy.Reasons for the co-occurrence of psychiatric conditions and epilepsy remain poorly understood.Aim We aimed to triangulate the relationship between epilepsy and psychiatric conditions to determine the extent and possible origins of these conditions.Methods Using nationwide Swedish health registries,we quantified the lifetime prevalence of psychiatric disorders in patients with epilepsy.We then used summarydata from genome-wide association studies to investigate whether the identified observational associations could be attributed to a shared underlying genetic aetiology using cross-trait linkage disequilibrium score regression.Finally,we assessed the potential bidirectional relationships using two-sample Mendelian randomisation.Results In a cohort of 7628495 individuals,we found that almost half of the 94435 individuals diagnosed with epilepsy were also diagnosed with a psychiatric condition in their lifetime(adjusted lifetime prevalence,44.09%;95%confidence interval(Cl)43.78%to 44.39%).We found evidence for a genetic correlation between epilepsy and some neurodevelopmental and psychiatric conditions.For example,we observed a genetic correlation between epilepsy and attention-deficit/hyperactivity disorder(r,=0.18,95%Cl 0.09 to 0.27,p<0.001)—a correlation that was more pronounced in focal epilepsy(r=0.23,95%CI 0.09 to 0.36,p<0.001).Findings from Mendelian randomisation using common genetic variants did not support bidirectional effects between epilepsy and neurodevelopmental or psychiatric conditions.Conclusions Psychiatric comorbidities are common in patients with epilepsy.Genetic correlations may partially explain some comorbidities;however,there is little evidence of a bidirectional relationship between the genetic liability of epilepsy and psychiatric conditions.These findings highlight the need to understand the role of environmental factors or rare genetic variations in the origins of psychiatric comorbidities in epilepsy.展开更多
The endometrium is a vital mucosal tissue which undergoes cyclical regeneration,differentiation,and remod-eling upon hormonal,cellular,and molecular signaling networks.Dysregulation of these processes can trigger a ra...The endometrium is a vital mucosal tissue which undergoes cyclical regeneration,differentiation,and remod-eling upon hormonal,cellular,and molecular signaling networks.Dysregulation of these processes can trigger a range of pathological conditions including chronic inflammatory disorders,hyperplastic lesions,malignancies,and infertility,necessitating the need for effective therapeutic interventions.Furthermore,we are still dependent on conventional treatment modalities which are often constrained by inefficient drug biodistribution,systemic toxicity,and emergence of therapeutic resistance.Recently,nanomedicines have gained tremendous attention in human healthcare,because they not only diagnose the disease but also deliver therapeutic agents to the targeted site without affecting healthy organs.There are numerous nanotechnology-based approaches that have been applied for clinical usage(s).In addition,recent advances in nanoparticle-based photothermal therapy,immu-nomodulatory approaches,and molecular imaging techniques have demonstrated considerable potential in refining both therapeutic and diagnostic strategies for endometrial pathologies.Herein,we reviewed a comprehensive analysis of nanotechnology-driven innovations in endometrial disease management,elucidating their mechanistic foundations,translational prospects,and future trajectories in endometrium and gynecological nanomedicine.展开更多
Milk-derived exosomes are widely used for diagnosis,delivery,imaging,and theranostic applications.Near-Infrared(NIR)based fluorescence bioimaging is an attractive and safer technique that is used for clinical applicat...Milk-derived exosomes are widely used for diagnosis,delivery,imaging,and theranostic applications.Near-Infrared(NIR)based fluorescence bioimaging is an attractive and safer technique that is used for clinical applications.However,almost all NIR imaging agents tend to have poor photostability,short half-life,nonspecific protein binding,and concentrationdependent aggregation(s).Therefore,there is an unmet clinical need to develop newer and safer modalities to package and deliver NIR imaging agents.Bovine milk exosomes are natural,biocompatible,safe,and efficient nanocarriers that facilitate the delivery of micro-and macromolecules.Herein,we developed an exosome-based NIR dye loaded nanoimaging formulation that offers improved solubility and photostability of NIR dye.Following the acetic acid based extracellular vesicle(EV)treatment method,we extracted the bovine milk exosomes from a variety of pasteurized grade milk.The EVs were screened for their physicochemical properties such as particle size and concentration and zeta potential.The stability of these exosomes was also determined under different conditions,including storage temperatures,pH,and salt concentrations.Next,indocyanine green,a model NIR dye was loaded into these exosomes(Exo-Glow)via a sonication method and further assessed for their improved fluorescence intensity and photostability using an IVIS imaging system.Initial screening suggested that size of the selected bovine milk exosomes was∼100−135 nm with an average particle concentration of 5.8×10^(2)particles/mL.Exo-Glow further demonstrated higher fluorescence intensity in cancer cells and tissues when compared to free dye.These results showed that Exo-Glow has the potential to serve as a safer NIR imaging tool for cancer cells/tissues.展开更多
Recent epidemiological studies have suggested a positive association between ultra-processed food consumption and breast cancer risk,although some studies also reported no association.Furthermore,the evidence regardin...Recent epidemiological studies have suggested a positive association between ultra-processed food consumption and breast cancer risk,although some studies also reported no association.Furthermore,the evidence regarding the associations between intake of food with lower degrees of processing and breast cancer risk is limited.Thus,we investigated the associations between dietary intake by degree of food processing and breast cancer risk,overall and by breast cancer subtypes in the European Prospective Investigation into Cancer and Nutrition(EPIC)study.Dietary intake of EPIC participants was assessed via questionnaires at baseline.More than 11,000 food ingredients were classified into four groups of food processing levels using the NOVA classification system:unprocessed/minimally processed(NOVA 1),culinary ingredients(NOVA 2),processed(NOVA 3)and ultra-processed(NOVA 4).Cox proportional hazards models were used to estimate hazard ratios(HRs)and 95%confidence intervals(CIs)of breast cancer per standard deviation increase in daily consumption(grams)of foods from each NOVA group.The current analysis included 14,933 breast cancer cases,diagnosed among the 318,686 EPIC female participants,(median follow-up of 14.9 years).No associations were found between breast cancer risk and the level of dietary intake from NOVA 1[HR_(per 1 SD)=0.99(95%CI 0.97-1.01)],NOVA 2[HR_(per 1 SD)=1.01(95%CI 0.98-1.03)]and NOVA 4[HR_(per 1 SD)=1.01(95%CI 0.99-1.03)]foods.However,a positive association was found between NOVA 3 and breast cancer risk[HR_(per 1 SD)=1.05(95%CI 1.03-1.07)]which became non-significant after adjustment for alcohol intake[HR_(per 1 SD)=1.01(95%CI 0.98-1.05)]or when beer and wine were excluded from this group[HR_(per 1 SD)=0.99(95%CI 0.97-1.01)].The associations did not differ by breast cancer subtype,menopausal status or body mass index.Findings from this large-scale prospective study suggest that the positive association between processed food intake and breast cancer risk was likely driven by alcoholic beverage consumption.展开更多
文摘Background: The physiological and biochemical demands of intense exercise elicit both muscle-based and systemic responses. The main adaptations to endurance exercise include the correction of electrolyte imbalance, a decrease in glycogen storage and the increase of oxidative stress, intestinal permeability, muscle damage, and systemic inflammatory response. Adaptations to exercise might be influenced by the gut microbiota, which plays an important role in the production, storage, and expenditure of energy obtained from the diet as well as in inflammation,redox reactions, and hydration status.Methods: A systematic and comprehensive search of electronic databases, including MEDLINE, Scopus, Clinical Trials.gov, Science Direct,Springer Link, and EMBASE was done. The search process was completed using the keywords: "endurance", "exercise", "immune response","microbiota", "nutrition", and "probiotics".Results: Reviewed literature supports the hypothesis that intestinal microbiota might be able to provide a measureable, effective marker of an athlete's immune function and that microbial composition analysis might also be sensitive enough to detect exercise-induced stress and metabolic disorders. The review also supports the hypothesis that modifying the microbiota through the use of probiotics could be an important therapeutic tool to improve athletes' overall general health, performance, and energy availability while controlling inflammation and redox levels.Conclusion: The present review provides a comprehensive overview of how gut microbiota may have a key role in controlling the oxidative stress and inflammatory responses as well as improving metabolism and energy expenditure during intense exercise.
基金This study was funded by the Medical Research Council(MC_UU_00011/6,MC_UU_00011/1).
文摘Introduction In their article entitled‘Investigating genetic causal relationships between blood pressure and anxiety,depressive symptoms,neuroticism and subjective well-being’,Cai and colleagues1 presented the results of a two-sample Mendelian randomisation2(MR)study examining associations between blood pressure traits(systolic,diastolic,hypertension and pulse pressure)and psychological traits(anxiety,depression,neuroticism and subjective well-being).After correction for multiple testing.
基金funded by the National Institute for Health Research School for Primary Care Research (NIHR SPCR)Funding from the British Heart Foundation,Cancer Research UK,Economic and Social Research Council,Medical Research Council,and the National Institute for Health Research,under the auspices of the UK Clinical Research Collaboration
文摘Theoretically, mesenchymal stem cells (MSCs) are very promising as adjuvanttherapy to alleviate coronavirus disease 2019 (COVID-19)-associated acute lunginjury and cytokine storm. Several published studies, which used MSCs toalleviate COVID-19-associated acute lung injury and cytokine storm, reportedpromising results. However, the evidence came from a case report, case series,and clinical trials with a limited number of participants. Therefore, more studiesare needed to get robust proof of MSC beneficial effects.
文摘We prospectively compared the safety and efficacy of bipolar transurethral enucleation of the prostate （TUEP） versus 160-W lithium triboride laser （LBO） photoselective vaporization of the prostate （PVP） for treating benign prostatic hyperplasia 〉70 ml.
文摘Salinity is a major stress that adversely affects growth and productivity in plants. There are species that tolerate this stresswithin the genus Atriplex. Four species, A. lampa, A. crenatifolia, A. nummularia and A. argentina were compared for their ionaccumulation and water relations under saline conditions. A greenhouse study was conducted by irrigating the four species with NaCIsolutions at concentrations 0%, 1%, 2% and 4% starting when plants were six months old. Plants were harvested 45 d after startingthe salinity treatments and analyzed for their ion contents. In the four Atriplex species, Na^＋ and Cl^- contents in plants increased, whileCa^2＋ and Mg^2＋ decreased with the increase of salinity in the irrigation solution. The results suggested that A. argentina and A.nummularia were able to maintain a higher leaf relative water content （RWC） at low leaf water potential, which was associated witha greater capacity of osmotic adjustment. A. lampa showed lower ion accumulation and minor osmotic adjustment than the otherspecies. It can be concluded that the accumulation of ions favors the lower osmotic potential and contributes to osmotic adjustment inthese halophytes.
文摘The ratio of the second-to-fourth digit length（2D：4D）has been shown to be sexually dimorphic,with males having lower mean than females and the ratio relates to masculinity and femininity in adults.2D：4D is influenced by digit growth pattern which is related to the ratio of prenatal androgen to estrogen levels in the later part of the first trimester.
文摘Objective: We employed a multidisciplinary approach incorporating theoretical ideas, clinical experience,psychology, physiology, traditional Chinese medicine(CM), modern practice of CM, and oncology to explore the effect of patients’ repression of negative emotions and traumatic events on breast cancer(BC) pathogenesis.Methods: BC female patients, older than 18 years of age, with available pathology reports who were treated at Rabin Medical Center were recruited. All participants completed questionnaires regarding medical history, behavioral tendencies, negative emotions, trauma, symptoms, and pathology(from a CM perspective). Data on tumor characteristics were collected from the pathology reports. The associations were examined using hierarchical binary logistic regressions.Results: A total of 155 BC patients were enrolled. The median age was 52 years, with a range of 26–79;95% were mothers;28% had estrogen receptor(ER)-negative BC, 52% had progesterone receptor(PR)-negative BC, 48% had human epidermal growth factor receptor 2-negative BC, and antigen Ki-67 ≥ 20%was reported for 52% of tumors. Statistically significant associations were found between the emotional markers(sense of motherhood failure, and lack of self-fulfillment), avoidance behavior, and physical symptoms that are related to emotional repression based on CM. Significant associations were also found between variables associated with physical symptoms of emotional repression, which involves the production and accumulation of non-substantial phlegm(i.e., ‘‘high-lipid Qi-like microscopic phlegm"),avoidance behavior which unconsciously uses ‘‘high-lipid Qi-like microscopic phlegm" in order to achieve emotional repression, and tumor parameters including tumor grade, PR status, and Ki-67.Patients with higher levels of ‘‘high-lipid Qi-like microscopic phlegm" were more likely to have tumors with worse prognosis(PR-negative, higher grade, and higher Ki-67).Conclusion: We demonstrated a relationship between emotional parameters, behavioral tendencies, CM parameters, and oncologic parameters in BC. Additional research is warranted to explore these associations and their relevance to clinical practice.
文摘<strong>Background:</strong> In an age of antiretroviral therapy, the life expectancy of children perinatally infected with Human Immunodeficiency Virus (HIV) has significantly increased. At the same time, however, pulmonary pathologies secondary to opportunistic infections have decreased thanks to increased diagnostics and access to antiretroviral therapy (ART). Despite this, in these children an immune dysregulation is maintained due to chronic infection. There is evidence that these patients have increased probability of presenting with abnormalities in pulmonary function, mainly with chronic obstructive clinical pictures (25% - 40% of perinatally infected adolescents display some anomaly in the spirometry), which predisposes them to increased risk of chronic pulmonary disease. Since lung development occurs mainly during infancy, patients perinatally infected with HIV may suffer consequences. This can be secondary to opportunistic infections, chronic inflammation due to the virus, and immunologic effects of ART, mainly in non-industrialized countries, where late diagnosis is frequent. <strong>Methodology:</strong> An analytical, observational, cross-sectional study was conducted at Roosevelt Hospital Pediatric infectious disease clinic, from January to December 2019. A sample of 76 patients was obtained, out of a population of 362 patients. A total of 62 subjects, who met the criterion of reproducibility in the spirometry, were analyzed. Results were analyzed with percentages and the association of variables using the chi-squared test (<em>χ</em><sup>2</sup>). <strong>Results:</strong> A decrease in pulmonary function was found in 34% of patients, mild obstructive pattern (16%) predominating. Significant association between basal viral load greater than 100,000 cp/ml and a decrease in Forced expiratory flow 25 - 75 (FEF 25-75) (<em>p</em> 0.046) and in relationship between forced expiratory volume and forced vital capacity (FEV1/ FVC <em>p</em> = 0.024) was observed, as well as a non-statistically significant relationship between advanced clinical stage at diagnosis and decreased pulmonary function. <strong>Conclusions:</strong> The prevalence of decreased pulmonary function related to advanced clinical stage and elevated basal viral load (>100,000 cps/ml) is higher than that reported in other studies (25%) and has an influence in the long-term decrease in pulmonary function.
文摘Stem cells have moved from lab to bedside, and many initial studies showed promising results. Therefore big companies are entering the business. However, most initial studies did not used controls to make sure of the efficacy of stem cells. Many phase-1 studies showed safety of stem cell therapies, when precaution measures were adapted. However, efficacy needs to be proven by randomized controlled trials (RCT) to exclude placebo effects. Recently, various RCTs for various conditions have been done with various contradictory results. Therefore, a meta-analysis is very useful to know whether a stem cell therapy really work for a certain condition. As various centres used various type of stem cells, various dose, and route of application, as well as different outcome measures with various results for one certain condition, sometimes it is difficult to conduct a meta-analysis when there is high heterogeneity, which is like pooling “apples” with “oranges” and “avocado” that will lead to a misleading conclusion. In many cases, where the studies are highly heterogeneous, and the heterogeneity can’t be identified, then a descriptive systematic review is the best solution to take a conclusion which protocol is the best and valuable to be standardized. Formerly it was believed that stem cells that are given to patients work by differentiating into the needed cells, and thus replacing damaged cell. However, recent evidence showed that only a few stem cells homed to the desired area, while a large amount went to various areas that were remote from the damaged area. Even though they were trapped in remote areas, the stem cells still exerted beneficial effects by remote signalling and secretion of various beneficial factors. Therefore, there are attempts to produce stem cell secretomes/metabolites to replace the stem cells, as metabolites are easier to handle and transported compared to the cells themselves. In addition, various studies worked on substitute tissue/organs “ex vivo” to be transplanted to replace a damaged organ. There are various means to produce a tissue/an organ/organoid “ex vivo” (tissue engineering) by using various stem cells, scaffold, and soluble factors, in various vessels from static vessel to bioreactors, and “on chips”. Though these attempts are in the initial stage, but some translational animal studies have been done. A more usual use of these “ex vivo” developed tissues/organs/organoids is for drug testing, such as toxicity testing, and for studying the mechanism of certain diseases that is directed toward the development of a cure of the diseases. In conclusion, many stem cell therapies have entered RCTs, but no standardized and approved protocol has been established, while organoids are usually used for drug testing and studying the mechanism of certain diseases.
文摘Over the past two decades, the neurobiological substrates of the reinforcement theory have been discussed in terms of a behavioral activation system (BAS) and a behavioral inhibition system (BIS). While the BAS has been conceptualized as both an activating system and an approach-related system, the empirical evidence for either approach remains inconclusive. In the current study we hypothesize that the inclusion of self-regulatory capacity contributes to a better understanding of the BAS. In a sample of 29 volunteers motor response inhibition elicited by a stop-signal task and heart rate variability (HRV) as a proxy of self-regulatory capacity were related to BAS scores (BIS/BAS scales [1]). Results show significant positive associations between inhibitory capacity and the sensitivity of the behavioral activation system, suggesting markers of self-regulation as components of the BAS.
文摘We hypothesize that individuals with genetic predisposition to Substance Use Disorder (SUD) may have greater likelihood of experiencing work related accidents. We further hypothesize that high risk populations will carry single or multiple polymorphisms associated with brain reward circuitry and/or brain reward cascade, including: Dopaminergic (i.e. DRD2 receptor genes);Serotonergic (i.e. 5-HTT2 receptor genes);Endorphinergic (i.e. pre-enkephalin genes);Gabergic (i.e. GABAA receptor genes);Neurotransmitter Metabolizing genes (i.e. MAO and COMT genes) among others (GARSRXTM). Analgesic addiction as well as “pseudoaddiction” must be treated to improve pain control and its management. We propose that non-pharmacological alternatives to pain relief, in high risk, addiction-prone individuals, are Electrotherapeutic Device(s) and Programs. We further propose patented KB220Z, a nutraceutical designed to release dopamine at the nucleus accumbens, will reduce craving behavior, in genetically programmed individuals. By utilizing both alternatives in DNA analyzed injured workers, a reduction in analgesic addiction (genuine or pseudo) leads to improved health and quicker return to work. We also hypothesize that this novel approach will impact costs related to injuries in the workforce. Effective management of chronic pain, especially in high addiction-prone workforce populations, is possible in spite of being particularly elusive. A series of factors encumber pain assessment and management, including analgesia addiction, pharmacogenomic response to pain medications, and genetically inherited factors involving gene polymorphisms. Additional research is required to test these stipulated hypotheses related to genetic proneness to addiction, but also proneness to accidents in the workplace and reduction of craving behavior. Our hypothesis that genotyping coupled with both KB220ZTM and the pharmaceutical-free Electrotherapy, will reduce iatrogenic induced analgesia addiction. This approach will achieve attainable effective pain management and quicker return to work. We propose outcomes such as the Reward Deficiency System SolutionTM may become an adjunct in the war against iatrogenic pain medication addiction.
文摘The mounting endemic of prescription iatrogenic opioid dependence in pain patients provoked this treatise about an alternative method that can be used to treat pain, improve function and reduce the risk of opioid dependence. It is well known that as well as the side effects reported for chronic opioid therapy, genetically predisposed individuals are at risk for opioid dependence. We propose the use of the Genetic Addiction Risk Score (GARS) assessment to identify patients early in treatment who should avoid narcotic pain medications. Primarily, this review will be an exploration of the mechanisms of action of an electrotherapeutic alternative to narcotic treatment that can be used to augment tissue healing and reduce the pain associated with human injuries and neuropathies. This particular electrotherapeutic device was developed at the Electronic Waveform Laboratory in Huntington Beach, California and is called the H-Wave? device. The primary effect of the H-Wave?device is stimulation (HWDS) of small diameter fibers of “red-slow-twitch” skeletal muscle. Mechanisms of action of HWDS have been investigated in both animal and human studies. They include edema reduction, induction of nitric oxide dependent augmented microcirculation and angiogenesis, small muscle contraction that eliminates transcapillary fluid shifts, reducing the painful effects of tetanizing fatigue and gradual loading of healing injured muscle tissue that helps repair and remodeling. A recent metaanalysis found a moderate-to-strong-positive effect of the HWDS in providing pain relief, reducing the requirement for pain medication, with the most robust effect being increased functionality. We are proposing that GARS can be used to identify those at risk of developing opioid dependence and that the need for opioid analgesia can be reduced by use of this electro therapeutic alternative to opioid analgesia in the treatment of pain and injuries.
基金the National Institutes of Health(1R01NS107607-01A1)Erik and Edith Fernstrom Foundation for Medical Research(2020-00321)+5 种基金Karolinska Institutet(2020-00160,2020-01172)the Swedish Society for Medical Research(RM21-0005)This study was also supported by the NIHR Biomedical Research Centre at the University of Bristol and University Hospitals Bristol and the Weston NHS Foundation TrustThe Medical Research Council(MRC)and the University of Bristol supported the MRC Integrative Epidemiology Unit(MC_UU_00011/1)NMD was supported by the Norwegian Research Council(grant number 295989)The Swedish Research Council(523-2010-1052)supports the(Psychiatry Sweden)register linkage.
文摘Background Psychiatric comorbidities are common in patients with epilepsy.Reasons for the co-occurrence of psychiatric conditions and epilepsy remain poorly understood.Aim We aimed to triangulate the relationship between epilepsy and psychiatric conditions to determine the extent and possible origins of these conditions.Methods Using nationwide Swedish health registries,we quantified the lifetime prevalence of psychiatric disorders in patients with epilepsy.We then used summarydata from genome-wide association studies to investigate whether the identified observational associations could be attributed to a shared underlying genetic aetiology using cross-trait linkage disequilibrium score regression.Finally,we assessed the potential bidirectional relationships using two-sample Mendelian randomisation.Results In a cohort of 7628495 individuals,we found that almost half of the 94435 individuals diagnosed with epilepsy were also diagnosed with a psychiatric condition in their lifetime(adjusted lifetime prevalence,44.09%;95%confidence interval(Cl)43.78%to 44.39%).We found evidence for a genetic correlation between epilepsy and some neurodevelopmental and psychiatric conditions.For example,we observed a genetic correlation between epilepsy and attention-deficit/hyperactivity disorder(r,=0.18,95%Cl 0.09 to 0.27,p<0.001)—a correlation that was more pronounced in focal epilepsy(r=0.23,95%CI 0.09 to 0.36,p<0.001).Findings from Mendelian randomisation using common genetic variants did not support bidirectional effects between epilepsy and neurodevelopmental or psychiatric conditions.Conclusions Psychiatric comorbidities are common in patients with epilepsy.Genetic correlations may partially explain some comorbidities;however,there is little evidence of a bidirectional relationship between the genetic liability of epilepsy and psychiatric conditions.These findings highlight the need to understand the role of environmental factors or rare genetic variations in the origins of psychiatric comorbidities in epilepsy.
基金support received by the NIH(U54MD019970/GM139727)CPRIT(RP210180/RP230419/RP250567)+1 种基金support by the NIH T34GM137854the Anusandhan National Research Founda-tion(ANRF/IRG/2024/000620/LS)Govt.of India for the funding support.
文摘The endometrium is a vital mucosal tissue which undergoes cyclical regeneration,differentiation,and remod-eling upon hormonal,cellular,and molecular signaling networks.Dysregulation of these processes can trigger a range of pathological conditions including chronic inflammatory disorders,hyperplastic lesions,malignancies,and infertility,necessitating the need for effective therapeutic interventions.Furthermore,we are still dependent on conventional treatment modalities which are often constrained by inefficient drug biodistribution,systemic toxicity,and emergence of therapeutic resistance.Recently,nanomedicines have gained tremendous attention in human healthcare,because they not only diagnose the disease but also deliver therapeutic agents to the targeted site without affecting healthy organs.There are numerous nanotechnology-based approaches that have been applied for clinical usage(s).In addition,recent advances in nanoparticle-based photothermal therapy,immu-nomodulatory approaches,and molecular imaging techniques have demonstrated considerable potential in refining both therapeutic and diagnostic strategies for endometrial pathologies.Herein,we reviewed a comprehensive analysis of nanotechnology-driven innovations in endometrial disease management,elucidating their mechanistic foundations,translational prospects,and future trajectories in endometrium and gynecological nanomedicine.
基金supported by Start-up from Division of Immunology and Microbiology,Medicine and Oncology ISU,School of Medicine,University of Texas Rio Grande Valley and NIH grants(SC1GM139727,R01 CA210192,and R01 CA206069)This research work utilized equipment and services of Integrated Cancer Research Center funded by CPRIT(RP210180 and RP230419)and UT System Star Award.
文摘Milk-derived exosomes are widely used for diagnosis,delivery,imaging,and theranostic applications.Near-Infrared(NIR)based fluorescence bioimaging is an attractive and safer technique that is used for clinical applications.However,almost all NIR imaging agents tend to have poor photostability,short half-life,nonspecific protein binding,and concentrationdependent aggregation(s).Therefore,there is an unmet clinical need to develop newer and safer modalities to package and deliver NIR imaging agents.Bovine milk exosomes are natural,biocompatible,safe,and efficient nanocarriers that facilitate the delivery of micro-and macromolecules.Herein,we developed an exosome-based NIR dye loaded nanoimaging formulation that offers improved solubility and photostability of NIR dye.Following the acetic acid based extracellular vesicle(EV)treatment method,we extracted the bovine milk exosomes from a variety of pasteurized grade milk.The EVs were screened for their physicochemical properties such as particle size and concentration and zeta potential.The stability of these exosomes was also determined under different conditions,including storage temperatures,pH,and salt concentrations.Next,indocyanine green,a model NIR dye was loaded into these exosomes(Exo-Glow)via a sonication method and further assessed for their improved fluorescence intensity and photostability using an IVIS imaging system.Initial screening suggested that size of the selected bovine milk exosomes was∼100−135 nm with an average particle concentration of 5.8×10^(2)particles/mL.Exo-Glow further demonstrated higher fluorescence intensity in cancer cells and tissues when compared to free dye.These results showed that Exo-Glow has the potential to serve as a safer NIR imaging tool for cancer cells/tissues.
基金supported by a Wellcome Trust PhD studentship in Molecular,Genetic and Lifecourse Epidemiology(224982/Z/22/Z).
文摘Recent epidemiological studies have suggested a positive association between ultra-processed food consumption and breast cancer risk,although some studies also reported no association.Furthermore,the evidence regarding the associations between intake of food with lower degrees of processing and breast cancer risk is limited.Thus,we investigated the associations between dietary intake by degree of food processing and breast cancer risk,overall and by breast cancer subtypes in the European Prospective Investigation into Cancer and Nutrition(EPIC)study.Dietary intake of EPIC participants was assessed via questionnaires at baseline.More than 11,000 food ingredients were classified into four groups of food processing levels using the NOVA classification system:unprocessed/minimally processed(NOVA 1),culinary ingredients(NOVA 2),processed(NOVA 3)and ultra-processed(NOVA 4).Cox proportional hazards models were used to estimate hazard ratios(HRs)and 95%confidence intervals(CIs)of breast cancer per standard deviation increase in daily consumption(grams)of foods from each NOVA group.The current analysis included 14,933 breast cancer cases,diagnosed among the 318,686 EPIC female participants,(median follow-up of 14.9 years).No associations were found between breast cancer risk and the level of dietary intake from NOVA 1[HR_(per 1 SD)=0.99(95%CI 0.97-1.01)],NOVA 2[HR_(per 1 SD)=1.01(95%CI 0.98-1.03)]and NOVA 4[HR_(per 1 SD)=1.01(95%CI 0.99-1.03)]foods.However,a positive association was found between NOVA 3 and breast cancer risk[HR_(per 1 SD)=1.05(95%CI 1.03-1.07)]which became non-significant after adjustment for alcohol intake[HR_(per 1 SD)=1.01(95%CI 0.98-1.05)]or when beer and wine were excluded from this group[HR_(per 1 SD)=0.99(95%CI 0.97-1.01)].The associations did not differ by breast cancer subtype,menopausal status or body mass index.Findings from this large-scale prospective study suggest that the positive association between processed food intake and breast cancer risk was likely driven by alcoholic beverage consumption.
