Infection is a public health problem and represents a spectrum of disease that can result in sepsis and septic shock.Sepsis is characterized by a dysregulated immune response to infection.Septic shock is the most seve...Infection is a public health problem and represents a spectrum of disease that can result in sepsis and septic shock.Sepsis is characterized by a dysregulated immune response to infection.Septic shock is the most severe form of sepsis which leads to distributive shock and high mortality rates.There have been significant advances in sepsis management mainly focusing on early identification and therapy.However,complicating matters is the lack of reliable diagnostic tools and the poor specificity and sensitivity of existing scoring tools i.e.,systemic inflammatory response syndrome criteria,sequential organ failure assessment(SOFA),or quick SOFA.These limitations have underscored the modest progress in reducing sepsis-related mortality.This review will focus on novel therapeutics such as oxidative stress targets,cytokine modulation,endothelial cell modulation,etc.,that are being conceptualized for the management of sepsis and septic shock.展开更多
Artemisia annua,known for its malarial properties,has been central to Madagascar's agricultural economy and traditional healing cultures for centuries.As demand for artemisinin-based treatments for malaria has con...Artemisia annua,known for its malarial properties,has been central to Madagascar's agricultural economy and traditional healing cultures for centuries.As demand for artemisinin-based treatments for malaria has continued to grow globally,Madagascar has emerged as a key supplier of Artemisia annua for global pharmaceutical markets,reinforcing the plant’s national significance.This paper explores the growth and evolution of Artemisia annua cultivation in the country,focusing especially on the recent introduction of synthetic artemisinin and the subsequent cultural,economic,and environmental impacts.It examines the challenges faced by Malagasy farmers and local healers with particular focus on issues such as artemisinin resistance,commercial exploitation,and the growing tension between traditional knowledge and modern biotechnology.Ultimately,this paper explores the complexities of balancing economic development,cultural preservation,and global health needs,offering insight into the broader implications for sustainable pharmaceutical sourcing and the future of traditional medicine in an increasingly globalized world.展开更多
Background:One-third of veterans returning from the 1990–1991 Gulf War reported a myriad of symptoms including cognitive dysfunction,skin rashes,musculoskeletal discomfort,and fatigue.This symptom cluster is now refe...Background:One-third of veterans returning from the 1990–1991 Gulf War reported a myriad of symptoms including cognitive dysfunction,skin rashes,musculoskeletal discomfort,and fatigue.This symptom cluster is now referred to as Gulf War Illness(GWI).As the underlying mechanisms of GWI have yet to be fully elucidated,diagnosis and treatment are based on symptomatic presentation.One confounding factor tied to the illness is the high presence of post-traumatic stress disorder(PTSD).Previous research efforts have demonstrated that both GWI and PTSD are associated with immunological dysfunction.As such,this research endeavor aimed to provide insight into the complex relationship between GWI symptoms,cytokine presence,and immune cell populations to pinpoint the impact of PTSD on these measures in GWI.Methods:Symptom measures were gathered through the Multidimensional fatigue inventory(MFI)and 36-item short form health survey(SF-36)scales and biological measures were obtained through cytokine&cytometry analysis.Subgrouping was conducted using Davidson Trauma Scale scores and the Structured Clinical Interview for Diagnostic and statistical manual of mental disorders(DSM)-5,into GWI with high probability of PTSD symptoms(GWIH)and GWI with low probability of PTSD symptoms(GWIL).Data was analyzed using analysis of variance(ANOVA)statistical analysis along with correlation graph analysis.We mapped correlations between immune cells and cytokine signaling measures,hormones and GWI symptom measures to identify patterns in regulation between the GWIH,GWIL,and healthy control groups.Results:GWI with comorbid PTSD symptoms resulted in poorer health outcomes compared with both healthy control(HC)and the GWIL subgroup.Significant differences were found in basophil levels of GWI compared with HC at peak exercise regardless of PTSD symptom comorbidity(ANOVA F=4.7,P=0.01)indicating its potential usage as a biomarker for general GWI from control.While the unique identification of GWI with PTSD symptoms was less clear,the GWIL subgroup was found to be delineated from both GWIH and HC on measures of IL-15 across an exercise challenge(ANOVA F>3.75,P<0.03).Additional differences in natural killer(NK)cell numbers and function highlight IL-15 as a potential biomarker of GWI in the absence of PTSD symptoms.Conclusions:We conclude that disentangling GWI and PTSD by defining trauma-based subgroups may aid in the identification of unique GWI biosignatures that can help to improve diagnosis and target treatment of GWI more effectively.展开更多
Emerging evidence indicates that childhood stressors, such as familial conflict, bullying, academic pressure, and traumatic events, can significantly worsen inflammatory skin conditions like atopic dermatitis (AD) and...Emerging evidence indicates that childhood stressors, such as familial conflict, bullying, academic pressure, and traumatic events, can significantly worsen inflammatory skin conditions like atopic dermatitis (AD) and psoriasis. This review explores the underlying neuroimmune pathways that link stress to skin inflammation in children, focusing on the role of the hypothalamic-pituitary-adrenal (HPA) axis and stress-induced cytokine production. Studies have shown that chronic psychological stress leads to dysregulation of the HPA axis, resulting in elevated cortisol levels, which paradoxically impair skin barrier function and upregulate pro-inflammatory cytokines such as IL-6, TNF-α, and IL-1β. Specific stressors, such as bullying, have been associated with heightened immune responses, increasing inflammation in the skin. For example, research has demonstrated that children who experience social stressors show elevated levels of C-reactive protein (CRP) and other markers of systemic inflammation, which directly correlate with skin condition flare-ups. Furthermore, exposure to early life stress has been linked to long-term alterations in immune function, perpetuating chronic inflammation even in the absence of ongoing stress. Future research should focus on longitudinal studies assessing how the timing, duration, and type of stressors influence skin condition severity, alongside evaluating interventions like cognitive-behavioral therapy (CBT) and stress management techniques. By addressing these childhood stressors, there is potential to not only mitigate skin condition flares but also reduce the long-term health consequences of chronic inflammation leading to therapeutic strategies that emphasize mental health alongside traditional dermatological treatments.展开更多
BACKGROUND Leg length discrepancy(LLD)following total hip arthroplasty(THA)is a common complaint,leading to decreased patient satisfaction.However,the effect of LLD before THA on outcomes and complications is not well...BACKGROUND Leg length discrepancy(LLD)following total hip arthroplasty(THA)is a common complaint,leading to decreased patient satisfaction.However,the effect of LLD before THA on outcomes and complications is not well defined.AIM To assess the effect of prior LLD on rates of falls,implant-related complications,stay length,readmissions,and implant survival following THA.METHODS A retrospective review of a nationwide insurance database was conducted from 2010 to 2021.All cases of THA and those with a prior diagnosis of LLD were identified.THA patients with LLD were matched to control patients 1:5 based on demographic and comorbidity profiles.Two-year fall rates and implant complications,lengths of stay,90-day readmissions,and time to revision were compared between cohorts.RESULTS A total of 2038 patients with LLD were matched to 10165 control patients.The LLD group showed significantly greater rates of falls[odds ratio(OR)=1.58;95%confidence interval(95%CI):1.24-2.01],dislocation(OR=2.61;95%CI:2.10-3.24),mechanical loosening(OR=4.58;95%CI:3.28-6.29),and periprosthetic fracture(OR=2.70;95%CI:1.96-3.72)compared to the control group(all P<0.001).Mean length of stay(LOS)was also significantly higher in the LLD group(3.1 days vs 2.8 days,P=0.034).No significant difference in 90-day readmission rates(7.75%vs 7.02%,P=0.244)was observed between the groups(P=0.244).Time to revision was significantly less in the LLD group(225 days vs 544 days,P<0.001).CONCLUSION LLD in patients having THA is related with significantly higher fall risk,rates of implant-related complications,LOS,and quicker time to revision.Identifying patients with LLD before their THA may help in identifying risks,better patient counselling,and more effective preoperative planning.However,the study have important limitations:Its design lacks information on the degree and cause of LLD,the time between diagnosis and surgery,and which leg with the discrepancy underwent the operation.Future well-designed studies should confirm the findings of this study.展开更多
Purpose:While the mental health impact of a prostate cancer diagnosis,including low-risk prostate cancer,is well-documented,the effect of pre-existing anxiety and/or depression on adherence to active surveillance prot...Purpose:While the mental health impact of a prostate cancer diagnosis,including low-risk prostate cancer,is well-documented,the effect of pre-existing anxiety and/or depression on adherence to active surveillance protocols in low-risk prostate cancer patients remains unclear.This study assessed the association between prior anxiety and/or depression and active surveillance adherence in men with low-risk prostate cancer.Methods:We conducted a retrospective,multicenter study involving 426 men diagnosed with low-risk prostate cancer who were recommended active surveillance as the primary management strategy.Active surveillance adherence was defined by completion of both a prostate-specific antigen test and a prostate biopsy within 18 months of diagnosis.Premature treatment was identified as definitive treatment,either through radiation therapy or radical prostatectomy.Results:Men with a prior mental health diagnosis were significantly less likely to adhere to active surveillance than those without such a diagnosis(27.6%vs.49.5%,p=0.006).These individuals had lower adherence rates for prostate-specific testing(58.6%vs.73.4%)and biopsy(27.6%vs.50.0%)and were more likely to abandon active surveillance in favor of immediate treatment(39.7%vs.25.0%,p=0.005).No significant differences were observed between patients with both anxiety and depression versus those with a single diagnosis.Conclusions:Pre-existing anxiety and/or depression is associated with reduced active surveillance adherence and a greater likelihood of premature treatment in men with low-risk prostate cancer.These findings highlight the importance of addressing psychiatric factors in lowrisk prostate cancer management and suggest avenues for future research.展开更多
This study describes the coral communities near Qatarand Abu Dhabi (UAE) ten years after the recurrent elevated temperature anomalies of 1996, 1998 and 2002 which resulted in the mass mortality of Acropora spp. Data d...This study describes the coral communities near Qatarand Abu Dhabi (UAE) ten years after the recurrent elevated temperature anomalies of 1996, 1998 and 2002 which resulted in the mass mortality of Acropora spp. Data derived from photo transects taken over a four-year period were analyzed to characterize the existing coral communities, to compare these to the pre- and post-disturbance communities in the adjacent waters near Dubai, and to project the time-frames required for the communities to return to pre-disturbance levels. The massive corals, dominated by Porites spp. and faviids, showed no long-terms affects associated with exposures to the three thermal anomalies;whereas acroporids, comprising 0% - 8% of the live coral cover, were in various stages of recovery. Projections indicated that acroporid regeneration will require 15 - 32 years to achieve the ≥40% pre-disturbance area cover. The existing communities are too small in size and number to be self-seeding;thus, they are dependent upon the recruitment of larvae from remote refuges of colonies that survived the thermal anomalies. Efforts to identify these refuges and to establish appropriate multi-national conservation programs shall become critical to the future survival of acroporids throughout the southeasternArabian Gulfas the projected regeneration times exceed the periods between disturbances, which are expected to occur more frequently as a result of global climate change.展开更多
Mast cells(MC)are found perivascularly in all tissues and may function as the sentinel immune cells sensing danger and then acting as the master conductor to orchestrate responses aimed at restoring homeostasis.Yet,MC...Mast cells(MC)are found perivascularly in all tissues and may function as the sentinel immune cells sensing danger and then acting as the master conductor to orchestrate responses aimed at restoring homeostasis.Yet,MC are best known for their critical role in allergic,but also inflammatory and other neuroimmune conditions.MC are stimulated by allergens,but also by many other environmental,neuroimmune,pathogenic and stress triggers.Stimulation of MC is called“activation”and is associated with the release of numerous neurohormonal,proinflammatory,tissue remodeling and vasoactive mediators via different secretory mechanisms,some of which do not involve the release of histamine and tryptase.However,mast cell activation and the subsequent responses may become excessive either because of persistent stimulation or dysregulation.Clinical and experimental evidence indicates that MC may be regulated by innate molecules,some derived from MC,themselves.However,discovery of such innate,natural,inhibitors has not been a priority even though they would substantially change the treatment of mast cell activation disorders(MCADs)since drugs that are available or under development focus on inducing MC apoptosis.Development of effective inhibitors of MC activation would require access to MC from healthy and MCAD subjects,preferably identical twins,that would allow differential investigation of the respective transcriptome.展开更多
Recent studies have suggested an evolving understanding of the association be-tween vaping,specifically electronic cigarette(e-cigarette)use,and the progre-ssion of atherosclerosis,a significant contributor to cardiov...Recent studies have suggested an evolving understanding of the association be-tween vaping,specifically electronic cigarette(e-cigarette)use,and the progre-ssion of atherosclerosis,a significant contributor to cardiovascular disease.Des-pite the prevailing perception of vaping as a safer alternative to traditional toba-cco smoking,accumulating evidence suggests that the aerosols emitted by e-cigarettes contain harmful constituents that may promote endothelial dysfunction,oxidative stress,inflammation,and dyslipidemia—key mechanisms implicated in atherosclerosis pathogenesis.While past research,including experimental studies and clinical investigations,has shed light on the potential cardiovascular risks associated with vaping,gaps in knowledge persist.Future research endeavors should focus on interpreting the long-term effects of vaping on atherosclerosis development and progression,exploring the impact of different e-cigarette formu-lations and user demographics,and identifying effective strategies for mitigating the cardiovascular consequences of vaping.By identifying and addressing these research gaps,we can enhance our understanding of the cardiovascular implica-tions of vaping and inform evidence-based interventions and policies to safe-guard public health.Core Tip:E-cigarette use has been linked to various cardiovascular risks,including the progression of atherosclerosis.Despite the perception of vaping as a safer alternative to smoking,evidence suggests that e-cigarette aerosols contain harmful substances that contribute to endothelial dysfunction,oxidative stress,inflammation,and dyslipidemia.These mechanisms are crucial in the development and progression of atherosclerosis.This review explores multiple facets of e-cigarettes and arterial health,focusing on the connection between vaping and atherosclerosis progression.It presents up-to-date evidence on pathophysiology and significant clinical implications,the impact of various constituents,and discusses contemporary public health strategies.展开更多
Proactive Semantic Interference (PSI) and failure to recover from PSI (frPSI), are novel constructs assessed by the LASSI-L. These measures are sensitive to cognitive changes in early Mild Cognitive Impairment (MCI) a...Proactive Semantic Interference (PSI) and failure to recover from PSI (frPSI), are novel constructs assessed by the LASSI-L. These measures are sensitive to cognitive changes in early Mild Cognitive Impairment (MCI) and preclinical AD determined by Aβ load using PET. The goal of this study was to compare a new computerized version of the LASSI-L (LASSI-Brief Computerized) to the standard paper-and-pencil version of the test. In this study, we examined 110 cognitively unimpaired (CU) older adults and 79 with amnestic MCI (aMCI) who were administered the paper-and-pencil form of the LASSI-L. Their performance was compared with 62 CU older adults and 52 aMCI participants examined using the LASSI-BC. After adjustment for covariates (degree of initial learning, sex, education, and language of evaluation) both the standard and computerized versions distinguished between aMCI and CU participants. The performance of CU and aMCI groups using either form was relatively commensurate. Importantly, an optimal combination of Cued B2 recall and Cued B1 intrusions on the LASSI-BC yielded an area under the ROC curve of .927, a sensitivity of 92.3% and specificity of 88.1%, relative to an area under the ROC curve of .815, a sensitivity of 72.5%, and a specificity of 79.1% obtained for the paper-and-pencil LASSI-L. Overall, the LASSI-BC was comparable, and in some ways, superior to the paper-and-pencil LASSI-L. Advantages of the LASSI-BC include a more standardized administration, suitability for remote assessment, and an automated scoring mechanism that can be verified by a built-in audio recording of responses.展开更多
Research Background: Atopic dermatitis (AD) is a chronic inflammatory skin condition in children that significantly impacts physical health and quality of life. Adherence to treatment regimens is crucial for effective...Research Background: Atopic dermatitis (AD) is a chronic inflammatory skin condition in children that significantly impacts physical health and quality of life. Adherence to treatment regimens is crucial for effective disease management but is often hindered by various psychosocial and socioeconomic barriers. Parental mental health issues, family dynamics, financial constraints, and limited access to specialized care contribute to inconsistent treatment adherence, exacerbating the condition. Purpose/Aim: The aim of this study is to explore the multifaceted barriers to treatment adherence in children with AD and evaluate the effectiveness of current interventions targeting these challenges. The study seeks to identify strategies that can improve adherence and health outcomes by addressing psychosocial and socioeconomic factors. Method: The method involves a comprehensive review of existing literature on the impact of psychosocial and socioeconomic factors on treatment adherence in children with AD. The study also examines various interventions designed to address these barriers, including community support programs, family-centered interventions, financial aid, integrated care models, and telehealth solutions. Results: Results indicate that psychosocial barriers, such as parental anxiety and depression, significantly hinder effective disease management. Family dynamics, including poor communication and single-parent households, complicate adherence efforts. Socioeconomic factors, such as financial constraints and limited healthcare access, further impede adherence. Interventions that address these barriers show promise in improving treatment adherence and health outcomes. Community support programs and family-centered interventions enhance parental mental health and family communication. Financial aid programs and integrated care models help mitigate economic and logistical challenges. Telehealth solutions improve access to specialized care, particularly in underserved areas. Conclusion: The study concludes that a holistic approach integrating medical treatment with psychosocial and socioeconomic support is essential for managing pediatric AD effectively. Policy recommendations include increased funding for community support programs, expanded telehealth services, and the integration of social services with medical care. Addressing these barriers comprehensively can enhance treatment adherence and improve the quality of life for children with AD. Further research should focus on long-term outcomes and diverse populations to refine these interventions and ensure they meet the needs of all affected children.展开更多
Skin diseases such as psoriasis, atopic dermatitis, burns, and other barrier insults pose ongoing therapeutic challenges, often requiring treatments that address both inflammation and skin barrier repair. The primary ...Skin diseases such as psoriasis, atopic dermatitis, burns, and other barrier insults pose ongoing therapeutic challenges, often requiring treatments that address both inflammation and skin barrier repair. The primary aim of this review is to provide a comprehensive overview of the potential benefits of sea buckthorn oil, derived from Hippophae rhamnoides, as a treatment for various skin diseases, detailing its anti-inflammatory properties, reporting benefits across several skin conditions, and highlighting challenges in formulation as well as preservation of the oil’s nutritional benefits. Drawing from a wide array of existing literature, this review investigates sea buckthorn oil’s rich composition of omega fatty acids, vitamins, and antioxidants, which may contribute to its therapeutic effects by modulating inflammatory pathways and enhancing skin barrier function. Clinical trials and patient case studies indicate that sea buckthorn oil shows promise in reducing erythema, inflammation, and improving skin sensitivity. However, challenges such as formulation stability, sourcing of quality oil, and variability in response to treatment across conditions need to be addressed. Future research should focus on optimizing formulations and conducting large-scale clinical trials to validate the therapeutic efficacy of sea buckthorn oil in the management of skin diseases. Additionally, further exploration of the regulatory mechanisms underlying its ability to modulate inflammation and repair the skin barrier is needed to fully elucidate its clinical potential. Sea buckthorn oil offers a novel and promising adjunctive treatment for psoriasis, atopic dermatitis, and wound-healing with significant potential to enhance therapeutic options for additional skin diseases.展开更多
Aldosterone mediates many of the physiological and pathophysiological/cardio-toxic effects of angiotensin II(Ang II). Its synthesis and secretion from the zona glomerulosa cells of the adrenal cortex, elevated in chro...Aldosterone mediates many of the physiological and pathophysiological/cardio-toxic effects of angiotensin II(Ang II). Its synthesis and secretion from the zona glomerulosa cells of the adrenal cortex, elevated in chronic heart failure(HF), is induced by Ang II type 1 receptors(AT1Rs). The AT1R is a G protein-coupled receptor, mainly coupling to Gq/11 proteins. However, it can also signal through β-arrestin-1(βarr1) or-2(βarr2), both of which mediate G protein-independent signaling. Over the past decade, a second, Gq/11 proteinindependent but βarr1-dependent signaling pathway emanating from the adrenocortical AT1R and leading to aldosterone production has become appreciated. Thus, it became apparent that AT1R antagonists that block both pathways equally well are warranted for fully effective aldosterone suppression in HF. This spurred the comparison of all of the currently marketed angiotensin receptor blockers(ARBs, AT1R antagonists or sartans) at blocking activation of the two signaling modes(G protein-, and βarr1-dependent) at the Ang IIactivated AT1R and hence, at suppression of aldosterone in vitro and in vivo. Although all agents are very potent inhibitors of G protein activation at the AT1R, candesartan and valsartan were uncovered to be the most potent ARBs at blocking βarr activation by Ang II and at suppressing aldosterone in vitro and in vivo in post-myocardial infarction HF animals. In contrast, irbesartan and losartan are virtually G protein-"biased" blockers at the human AT1R, with very low efficacy for βarr inhibition and aldosterone suppression. Therefore, candesartan and valsartan(and other, structurally similar compounds) may be the most preferred ARB agents for HF pharmacotherapy, as well as for treatment of other conditions characterized by elevated aldosterone.展开更多
Atherosclerosis is a chronic inflammatory disease associated with cardiovascular dysfunction including myocardial infarction, unstable angina, sudden cardiac death, stroke and peripheral thromboses. It has been predic...Atherosclerosis is a chronic inflammatory disease associated with cardiovascular dysfunction including myocardial infarction, unstable angina, sudden cardiac death, stroke and peripheral thromboses. It has been predicted that atherosclerosis will be the primary cause of death in the world by 2020. Atherogenesis is initiated by endothelial injury due to oxidative stress associated with cardiovascular risk factors including diabetes mellitus, hypertension, cigarette smoking, dyslipidemia, obesity, and metabolic syndrome. The impairment of the endothelium associated with cardiovascular risk factors creates an imbalance between vasodilating and vasoconstricting factors, in particular, an increase in angiotensin Ⅱ(Ang Ⅱ) and a decrease in nitric oxide. The renin-angiotensin system(RAS), and its primary mediator Ang Ⅱ, also have a direct influence on the progression of the atherosclerotic process via effects on endothelial function, inflammation, fibrinolytic balance, and plaque stability. Anti-inflammatory agents [statins, secretory phospholipase A2 inhibitor, lipoprotein-associated phospholipase A2 inhibitor, 5-lipoxygenase activating protein, chemokine motif ligand-2, C-C chemokine motif receptor 2 pathway inhibitors, methotrexate, IL-1 pathway inhibitor and RAS inhibitors(angiotensin-converting enzyme inhibitors)], Ang Ⅱ receptor blockers and ranin inhibitors may slow inflammatory processes and disease progression. Several studies in human using anti-inflammatory agents and RAS inhibitors revealed vascular benefits and reduced progression of coronary atherosclerosis in patients with stable angina pectoris; decreased vascular inflammatory markers, improved common carotid intima-media thickness and plaque volume in patients with diagnosed atherosclerosis. Recent preclinical studies have demonstrated therapeutic efficacy of vitamin D analogs paricalcitol in Apo E-deficient atherosclerotic mice.展开更多
Epidemiological, preclinical and clinical studies es-tablished the association between high alcohol con-sumption and hypertension. However the mechanism through which alcohol raises blood pressure remains elusive. Sev...Epidemiological, preclinical and clinical studies es-tablished the association between high alcohol con-sumption and hypertension. However the mechanism through which alcohol raises blood pressure remains elusive. Several possible mechanisms have been pro-posed such as an imbalance of the central nervous system, impairment of the baroreceptors, enhanced sympathetic activity, stimulation of the renin-angio-tensin-aldosterone system, increased cortisol levels, increased vascular reactivity due to increase in intracel-lular calcium levels, stimulation of the endothelium to release vasoconstrictors and loss of relaxation due to inflammation and oxidative injury of the endothelium leading to inhibition of endothelium-dependent nitric oxide production. Loss of relaxation due to inflamma-tion and oxidative injury of the endothelium by angio-tensin II leading to inhibition of endothelium-dependent nitric oxide production is the major contributors of the alcohol-induced hypertension. For the prevention of alcohol-induced hypertension is to reduce the amount of alcohol intake. Physical conditioning/exercise trainingis one of the most important strategies to prevent/treat chronic alcohol-induced hypertension on physiological basis. The efficacious pharmacologic treatment includes the angiotensin-converting enzyme(ACE) inhibitors or angiotensin Ⅱ type 1 receptor blockers(ARBs) which have antioxidant activity and calcium channel blockers. The most effective prevention and treatment of alcohol-induced hypertension is physical exercise and the use of ACE inhibitors or ARBs in the展开更多
Neurocysticercosis(NCC) is one of the seven neglected endemic zoonoses targeted by the World Health Organization.It is considered a common infection of the nervous system caused by the Tanenia solium and is known to b...Neurocysticercosis(NCC) is one of the seven neglected endemic zoonoses targeted by the World Health Organization.It is considered a common infection of the nervous system caused by the Tanenia solium and is known to be the primary cause of preventable epilepsy in many developing countries.NCC is commonly resulted by the ingestion of Tanenia solium eggs after consuming undercooked pork,or contaminated water.The parasite can grow in the brain and spinal cord within the nervous system,causing severe headache and seizures beside other pathological manifestations.Immigration and international travel to endemic countries has made this disease common in the United States.NCC can be diagnosed with computed tomography and magnetic resonance imaging of the brain.The treatment of the NCC including cysticidal drugs(eg.,albendazole and praziquantel),and neurosurgical procedure,depending upon a the situation.A patient of Asian origin came to our clinic with complaints of dizziness,headaches and episodes seizures for the past twelve years without proper diagnosis.The computed tomography and magnetic resonance imaging scans indicated multilobulated cystic mass in the brain with the suspicion of neurocysticercosis.展开更多
Heart failure(HF), the number one cause of death in the western world, is caused by the insufficient performance of the heart leading to tissue underperfusion in response to an injury or insult. It comprises complex i...Heart failure(HF), the number one cause of death in the western world, is caused by the insufficient performance of the heart leading to tissue underperfusion in response to an injury or insult. It comprises complex interactions between important neurohormonal mechanisms that try but ultimately fail to sustain cardiac output. The most prominent such mechanism is the sympathetic(adrenergic) nervous system(SNS), whose activity and outflow are greatly elevated in HF. SNS hyperactivity confers significant toxicity to the failing heart and markedly increases HF morbidity and mortality via excessive activation of adrenergic receptors, which are G protein-coupled receptors. Thus, ligand binding induces their coupling to heterotrimeric G proteins that transduce intracellular signals. G protein signaling is turned-off by the agonist-bound receptor phosphorylation courtesy of G protein-coupled receptor kinases(GRKs), followed by βarrestin binding, which prevents the GRK-phosphorylated receptor from further interaction with the G proteins and simultaneously leads it inside the cell(receptor sequestration). Recent evidence indicates that adrenal GRK2 and βarrestins can regulate adrenal catecholamine secretion, thereby modulating SNS activity in HF. The present review gives an account of all these studies on adrenal GRKs and βarrestins in HF and discusses the exciting new therapeutic possibilities for chronic HF offered by targeting these proteins pharmacologically.展开更多
文摘Infection is a public health problem and represents a spectrum of disease that can result in sepsis and septic shock.Sepsis is characterized by a dysregulated immune response to infection.Septic shock is the most severe form of sepsis which leads to distributive shock and high mortality rates.There have been significant advances in sepsis management mainly focusing on early identification and therapy.However,complicating matters is the lack of reliable diagnostic tools and the poor specificity and sensitivity of existing scoring tools i.e.,systemic inflammatory response syndrome criteria,sequential organ failure assessment(SOFA),or quick SOFA.These limitations have underscored the modest progress in reducing sepsis-related mortality.This review will focus on novel therapeutics such as oxidative stress targets,cytokine modulation,endothelial cell modulation,etc.,that are being conceptualized for the management of sepsis and septic shock.
文摘Artemisia annua,known for its malarial properties,has been central to Madagascar's agricultural economy and traditional healing cultures for centuries.As demand for artemisinin-based treatments for malaria has continued to grow globally,Madagascar has emerged as a key supplier of Artemisia annua for global pharmaceutical markets,reinforcing the plant’s national significance.This paper explores the growth and evolution of Artemisia annua cultivation in the country,focusing especially on the recent introduction of synthetic artemisinin and the subsequent cultural,economic,and environmental impacts.It examines the challenges faced by Malagasy farmers and local healers with particular focus on issues such as artemisinin resistance,commercial exploitation,and the growing tension between traditional knowledge and modern biotechnology.Ultimately,this paper explores the complexities of balancing economic development,cultural preservation,and global health needs,offering insight into the broader implications for sustainable pharmaceutical sourcing and the future of traditional medicine in an increasingly globalized world.
基金suppor ted by the US Depar tment of Defense Congressionally Directed Medical Research Program (CDMRP)awards (http://cdmrp.army.mil/) W81XWH-16-1-0632 (Craddock PI),W81XWH-16-1-0552 (Craddock PI),W81XWH-18-1-0549 (Sullivan PI),W81XWH-13-2-0072 (Sullivan PI),and W81XWH-09-2-0071 (Klimas PI)a Veterans Affairs Merit Award (4987.69) to Dr.Nancy Klimas。
文摘Background:One-third of veterans returning from the 1990–1991 Gulf War reported a myriad of symptoms including cognitive dysfunction,skin rashes,musculoskeletal discomfort,and fatigue.This symptom cluster is now referred to as Gulf War Illness(GWI).As the underlying mechanisms of GWI have yet to be fully elucidated,diagnosis and treatment are based on symptomatic presentation.One confounding factor tied to the illness is the high presence of post-traumatic stress disorder(PTSD).Previous research efforts have demonstrated that both GWI and PTSD are associated with immunological dysfunction.As such,this research endeavor aimed to provide insight into the complex relationship between GWI symptoms,cytokine presence,and immune cell populations to pinpoint the impact of PTSD on these measures in GWI.Methods:Symptom measures were gathered through the Multidimensional fatigue inventory(MFI)and 36-item short form health survey(SF-36)scales and biological measures were obtained through cytokine&cytometry analysis.Subgrouping was conducted using Davidson Trauma Scale scores and the Structured Clinical Interview for Diagnostic and statistical manual of mental disorders(DSM)-5,into GWI with high probability of PTSD symptoms(GWIH)and GWI with low probability of PTSD symptoms(GWIL).Data was analyzed using analysis of variance(ANOVA)statistical analysis along with correlation graph analysis.We mapped correlations between immune cells and cytokine signaling measures,hormones and GWI symptom measures to identify patterns in regulation between the GWIH,GWIL,and healthy control groups.Results:GWI with comorbid PTSD symptoms resulted in poorer health outcomes compared with both healthy control(HC)and the GWIL subgroup.Significant differences were found in basophil levels of GWI compared with HC at peak exercise regardless of PTSD symptom comorbidity(ANOVA F=4.7,P=0.01)indicating its potential usage as a biomarker for general GWI from control.While the unique identification of GWI with PTSD symptoms was less clear,the GWIL subgroup was found to be delineated from both GWIH and HC on measures of IL-15 across an exercise challenge(ANOVA F>3.75,P<0.03).Additional differences in natural killer(NK)cell numbers and function highlight IL-15 as a potential biomarker of GWI in the absence of PTSD symptoms.Conclusions:We conclude that disentangling GWI and PTSD by defining trauma-based subgroups may aid in the identification of unique GWI biosignatures that can help to improve diagnosis and target treatment of GWI more effectively.
文摘Emerging evidence indicates that childhood stressors, such as familial conflict, bullying, academic pressure, and traumatic events, can significantly worsen inflammatory skin conditions like atopic dermatitis (AD) and psoriasis. This review explores the underlying neuroimmune pathways that link stress to skin inflammation in children, focusing on the role of the hypothalamic-pituitary-adrenal (HPA) axis and stress-induced cytokine production. Studies have shown that chronic psychological stress leads to dysregulation of the HPA axis, resulting in elevated cortisol levels, which paradoxically impair skin barrier function and upregulate pro-inflammatory cytokines such as IL-6, TNF-α, and IL-1β. Specific stressors, such as bullying, have been associated with heightened immune responses, increasing inflammation in the skin. For example, research has demonstrated that children who experience social stressors show elevated levels of C-reactive protein (CRP) and other markers of systemic inflammation, which directly correlate with skin condition flare-ups. Furthermore, exposure to early life stress has been linked to long-term alterations in immune function, perpetuating chronic inflammation even in the absence of ongoing stress. Future research should focus on longitudinal studies assessing how the timing, duration, and type of stressors influence skin condition severity, alongside evaluating interventions like cognitive-behavioral therapy (CBT) and stress management techniques. By addressing these childhood stressors, there is potential to not only mitigate skin condition flares but also reduce the long-term health consequences of chronic inflammation leading to therapeutic strategies that emphasize mental health alongside traditional dermatological treatments.
文摘BACKGROUND Leg length discrepancy(LLD)following total hip arthroplasty(THA)is a common complaint,leading to decreased patient satisfaction.However,the effect of LLD before THA on outcomes and complications is not well defined.AIM To assess the effect of prior LLD on rates of falls,implant-related complications,stay length,readmissions,and implant survival following THA.METHODS A retrospective review of a nationwide insurance database was conducted from 2010 to 2021.All cases of THA and those with a prior diagnosis of LLD were identified.THA patients with LLD were matched to control patients 1:5 based on demographic and comorbidity profiles.Two-year fall rates and implant complications,lengths of stay,90-day readmissions,and time to revision were compared between cohorts.RESULTS A total of 2038 patients with LLD were matched to 10165 control patients.The LLD group showed significantly greater rates of falls[odds ratio(OR)=1.58;95%confidence interval(95%CI):1.24-2.01],dislocation(OR=2.61;95%CI:2.10-3.24),mechanical loosening(OR=4.58;95%CI:3.28-6.29),and periprosthetic fracture(OR=2.70;95%CI:1.96-3.72)compared to the control group(all P<0.001).Mean length of stay(LOS)was also significantly higher in the LLD group(3.1 days vs 2.8 days,P=0.034).No significant difference in 90-day readmission rates(7.75%vs 7.02%,P=0.244)was observed between the groups(P=0.244).Time to revision was significantly less in the LLD group(225 days vs 544 days,P<0.001).CONCLUSION LLD in patients having THA is related with significantly higher fall risk,rates of implant-related complications,LOS,and quicker time to revision.Identifying patients with LLD before their THA may help in identifying risks,better patient counselling,and more effective preoperative planning.However,the study have important limitations:Its design lacks information on the degree and cause of LLD,the time between diagnosis and surgery,and which leg with the discrepancy underwent the operation.Future well-designed studies should confirm the findings of this study.
文摘Purpose:While the mental health impact of a prostate cancer diagnosis,including low-risk prostate cancer,is well-documented,the effect of pre-existing anxiety and/or depression on adherence to active surveillance protocols in low-risk prostate cancer patients remains unclear.This study assessed the association between prior anxiety and/or depression and active surveillance adherence in men with low-risk prostate cancer.Methods:We conducted a retrospective,multicenter study involving 426 men diagnosed with low-risk prostate cancer who were recommended active surveillance as the primary management strategy.Active surveillance adherence was defined by completion of both a prostate-specific antigen test and a prostate biopsy within 18 months of diagnosis.Premature treatment was identified as definitive treatment,either through radiation therapy or radical prostatectomy.Results:Men with a prior mental health diagnosis were significantly less likely to adhere to active surveillance than those without such a diagnosis(27.6%vs.49.5%,p=0.006).These individuals had lower adherence rates for prostate-specific testing(58.6%vs.73.4%)and biopsy(27.6%vs.50.0%)and were more likely to abandon active surveillance in favor of immediate treatment(39.7%vs.25.0%,p=0.005).No significant differences were observed between patients with both anxiety and depression versus those with a single diagnosis.Conclusions:Pre-existing anxiety and/or depression is associated with reduced active surveillance adherence and a greater likelihood of premature treatment in men with low-risk prostate cancer.These findings highlight the importance of addressing psychiatric factors in lowrisk prostate cancer management and suggest avenues for future research.
文摘This study describes the coral communities near Qatarand Abu Dhabi (UAE) ten years after the recurrent elevated temperature anomalies of 1996, 1998 and 2002 which resulted in the mass mortality of Acropora spp. Data derived from photo transects taken over a four-year period were analyzed to characterize the existing coral communities, to compare these to the pre- and post-disturbance communities in the adjacent waters near Dubai, and to project the time-frames required for the communities to return to pre-disturbance levels. The massive corals, dominated by Porites spp. and faviids, showed no long-terms affects associated with exposures to the three thermal anomalies;whereas acroporids, comprising 0% - 8% of the live coral cover, were in various stages of recovery. Projections indicated that acroporid regeneration will require 15 - 32 years to achieve the ≥40% pre-disturbance area cover. The existing communities are too small in size and number to be self-seeding;thus, they are dependent upon the recruitment of larvae from remote refuges of colonies that survived the thermal anomalies. Efforts to identify these refuges and to establish appropriate multi-national conservation programs shall become critical to the future survival of acroporids throughout the southeasternArabian Gulfas the projected regeneration times exceed the periods between disturbances, which are expected to occur more frequently as a result of global climate change.
文摘Mast cells(MC)are found perivascularly in all tissues and may function as the sentinel immune cells sensing danger and then acting as the master conductor to orchestrate responses aimed at restoring homeostasis.Yet,MC are best known for their critical role in allergic,but also inflammatory and other neuroimmune conditions.MC are stimulated by allergens,but also by many other environmental,neuroimmune,pathogenic and stress triggers.Stimulation of MC is called“activation”and is associated with the release of numerous neurohormonal,proinflammatory,tissue remodeling and vasoactive mediators via different secretory mechanisms,some of which do not involve the release of histamine and tryptase.However,mast cell activation and the subsequent responses may become excessive either because of persistent stimulation or dysregulation.Clinical and experimental evidence indicates that MC may be regulated by innate molecules,some derived from MC,themselves.However,discovery of such innate,natural,inhibitors has not been a priority even though they would substantially change the treatment of mast cell activation disorders(MCADs)since drugs that are available or under development focus on inducing MC apoptosis.Development of effective inhibitors of MC activation would require access to MC from healthy and MCAD subjects,preferably identical twins,that would allow differential investigation of the respective transcriptome.
文摘Recent studies have suggested an evolving understanding of the association be-tween vaping,specifically electronic cigarette(e-cigarette)use,and the progre-ssion of atherosclerosis,a significant contributor to cardiovascular disease.Des-pite the prevailing perception of vaping as a safer alternative to traditional toba-cco smoking,accumulating evidence suggests that the aerosols emitted by e-cigarettes contain harmful constituents that may promote endothelial dysfunction,oxidative stress,inflammation,and dyslipidemia—key mechanisms implicated in atherosclerosis pathogenesis.While past research,including experimental studies and clinical investigations,has shed light on the potential cardiovascular risks associated with vaping,gaps in knowledge persist.Future research endeavors should focus on interpreting the long-term effects of vaping on atherosclerosis development and progression,exploring the impact of different e-cigarette formu-lations and user demographics,and identifying effective strategies for mitigating the cardiovascular consequences of vaping.By identifying and addressing these research gaps,we can enhance our understanding of the cardiovascular implica-tions of vaping and inform evidence-based interventions and policies to safe-guard public health.Core Tip:E-cigarette use has been linked to various cardiovascular risks,including the progression of atherosclerosis.Despite the perception of vaping as a safer alternative to smoking,evidence suggests that e-cigarette aerosols contain harmful substances that contribute to endothelial dysfunction,oxidative stress,inflammation,and dyslipidemia.These mechanisms are crucial in the development and progression of atherosclerosis.This review explores multiple facets of e-cigarettes and arterial health,focusing on the connection between vaping and atherosclerosis progression.It presents up-to-date evidence on pathophysiology and significant clinical implications,the impact of various constituents,and discusses contemporary public health strategies.
文摘Proactive Semantic Interference (PSI) and failure to recover from PSI (frPSI), are novel constructs assessed by the LASSI-L. These measures are sensitive to cognitive changes in early Mild Cognitive Impairment (MCI) and preclinical AD determined by Aβ load using PET. The goal of this study was to compare a new computerized version of the LASSI-L (LASSI-Brief Computerized) to the standard paper-and-pencil version of the test. In this study, we examined 110 cognitively unimpaired (CU) older adults and 79 with amnestic MCI (aMCI) who were administered the paper-and-pencil form of the LASSI-L. Their performance was compared with 62 CU older adults and 52 aMCI participants examined using the LASSI-BC. After adjustment for covariates (degree of initial learning, sex, education, and language of evaluation) both the standard and computerized versions distinguished between aMCI and CU participants. The performance of CU and aMCI groups using either form was relatively commensurate. Importantly, an optimal combination of Cued B2 recall and Cued B1 intrusions on the LASSI-BC yielded an area under the ROC curve of .927, a sensitivity of 92.3% and specificity of 88.1%, relative to an area under the ROC curve of .815, a sensitivity of 72.5%, and a specificity of 79.1% obtained for the paper-and-pencil LASSI-L. Overall, the LASSI-BC was comparable, and in some ways, superior to the paper-and-pencil LASSI-L. Advantages of the LASSI-BC include a more standardized administration, suitability for remote assessment, and an automated scoring mechanism that can be verified by a built-in audio recording of responses.
文摘Research Background: Atopic dermatitis (AD) is a chronic inflammatory skin condition in children that significantly impacts physical health and quality of life. Adherence to treatment regimens is crucial for effective disease management but is often hindered by various psychosocial and socioeconomic barriers. Parental mental health issues, family dynamics, financial constraints, and limited access to specialized care contribute to inconsistent treatment adherence, exacerbating the condition. Purpose/Aim: The aim of this study is to explore the multifaceted barriers to treatment adherence in children with AD and evaluate the effectiveness of current interventions targeting these challenges. The study seeks to identify strategies that can improve adherence and health outcomes by addressing psychosocial and socioeconomic factors. Method: The method involves a comprehensive review of existing literature on the impact of psychosocial and socioeconomic factors on treatment adherence in children with AD. The study also examines various interventions designed to address these barriers, including community support programs, family-centered interventions, financial aid, integrated care models, and telehealth solutions. Results: Results indicate that psychosocial barriers, such as parental anxiety and depression, significantly hinder effective disease management. Family dynamics, including poor communication and single-parent households, complicate adherence efforts. Socioeconomic factors, such as financial constraints and limited healthcare access, further impede adherence. Interventions that address these barriers show promise in improving treatment adherence and health outcomes. Community support programs and family-centered interventions enhance parental mental health and family communication. Financial aid programs and integrated care models help mitigate economic and logistical challenges. Telehealth solutions improve access to specialized care, particularly in underserved areas. Conclusion: The study concludes that a holistic approach integrating medical treatment with psychosocial and socioeconomic support is essential for managing pediatric AD effectively. Policy recommendations include increased funding for community support programs, expanded telehealth services, and the integration of social services with medical care. Addressing these barriers comprehensively can enhance treatment adherence and improve the quality of life for children with AD. Further research should focus on long-term outcomes and diverse populations to refine these interventions and ensure they meet the needs of all affected children.
文摘Skin diseases such as psoriasis, atopic dermatitis, burns, and other barrier insults pose ongoing therapeutic challenges, often requiring treatments that address both inflammation and skin barrier repair. The primary aim of this review is to provide a comprehensive overview of the potential benefits of sea buckthorn oil, derived from Hippophae rhamnoides, as a treatment for various skin diseases, detailing its anti-inflammatory properties, reporting benefits across several skin conditions, and highlighting challenges in formulation as well as preservation of the oil’s nutritional benefits. Drawing from a wide array of existing literature, this review investigates sea buckthorn oil’s rich composition of omega fatty acids, vitamins, and antioxidants, which may contribute to its therapeutic effects by modulating inflammatory pathways and enhancing skin barrier function. Clinical trials and patient case studies indicate that sea buckthorn oil shows promise in reducing erythema, inflammation, and improving skin sensitivity. However, challenges such as formulation stability, sourcing of quality oil, and variability in response to treatment across conditions need to be addressed. Future research should focus on optimizing formulations and conducting large-scale clinical trials to validate the therapeutic efficacy of sea buckthorn oil in the management of skin diseases. Additionally, further exploration of the regulatory mechanisms underlying its ability to modulate inflammation and repair the skin barrier is needed to fully elucidate its clinical potential. Sea buckthorn oil offers a novel and promising adjunctive treatment for psoriasis, atopic dermatitis, and wound-healing with significant potential to enhance therapeutic options for additional skin diseases.
文摘Aldosterone mediates many of the physiological and pathophysiological/cardio-toxic effects of angiotensin II(Ang II). Its synthesis and secretion from the zona glomerulosa cells of the adrenal cortex, elevated in chronic heart failure(HF), is induced by Ang II type 1 receptors(AT1Rs). The AT1R is a G protein-coupled receptor, mainly coupling to Gq/11 proteins. However, it can also signal through β-arrestin-1(βarr1) or-2(βarr2), both of which mediate G protein-independent signaling. Over the past decade, a second, Gq/11 proteinindependent but βarr1-dependent signaling pathway emanating from the adrenocortical AT1R and leading to aldosterone production has become appreciated. Thus, it became apparent that AT1R antagonists that block both pathways equally well are warranted for fully effective aldosterone suppression in HF. This spurred the comparison of all of the currently marketed angiotensin receptor blockers(ARBs, AT1R antagonists or sartans) at blocking activation of the two signaling modes(G protein-, and βarr1-dependent) at the Ang IIactivated AT1R and hence, at suppression of aldosterone in vitro and in vivo. Although all agents are very potent inhibitors of G protein activation at the AT1R, candesartan and valsartan were uncovered to be the most potent ARBs at blocking βarr activation by Ang II and at suppressing aldosterone in vitro and in vivo in post-myocardial infarction HF animals. In contrast, irbesartan and losartan are virtually G protein-"biased" blockers at the human AT1R, with very low efficacy for βarr inhibition and aldosterone suppression. Therefore, candesartan and valsartan(and other, structurally similar compounds) may be the most preferred ARB agents for HF pharmacotherapy, as well as for treatment of other conditions characterized by elevated aldosterone.
文摘Atherosclerosis is a chronic inflammatory disease associated with cardiovascular dysfunction including myocardial infarction, unstable angina, sudden cardiac death, stroke and peripheral thromboses. It has been predicted that atherosclerosis will be the primary cause of death in the world by 2020. Atherogenesis is initiated by endothelial injury due to oxidative stress associated with cardiovascular risk factors including diabetes mellitus, hypertension, cigarette smoking, dyslipidemia, obesity, and metabolic syndrome. The impairment of the endothelium associated with cardiovascular risk factors creates an imbalance between vasodilating and vasoconstricting factors, in particular, an increase in angiotensin Ⅱ(Ang Ⅱ) and a decrease in nitric oxide. The renin-angiotensin system(RAS), and its primary mediator Ang Ⅱ, also have a direct influence on the progression of the atherosclerotic process via effects on endothelial function, inflammation, fibrinolytic balance, and plaque stability. Anti-inflammatory agents [statins, secretory phospholipase A2 inhibitor, lipoprotein-associated phospholipase A2 inhibitor, 5-lipoxygenase activating protein, chemokine motif ligand-2, C-C chemokine motif receptor 2 pathway inhibitors, methotrexate, IL-1 pathway inhibitor and RAS inhibitors(angiotensin-converting enzyme inhibitors)], Ang Ⅱ receptor blockers and ranin inhibitors may slow inflammatory processes and disease progression. Several studies in human using anti-inflammatory agents and RAS inhibitors revealed vascular benefits and reduced progression of coronary atherosclerosis in patients with stable angina pectoris; decreased vascular inflammatory markers, improved common carotid intima-media thickness and plaque volume in patients with diagnosed atherosclerosis. Recent preclinical studies have demonstrated therapeutic efficacy of vitamin D analogs paricalcitol in Apo E-deficient atherosclerotic mice.
文摘Epidemiological, preclinical and clinical studies es-tablished the association between high alcohol con-sumption and hypertension. However the mechanism through which alcohol raises blood pressure remains elusive. Several possible mechanisms have been pro-posed such as an imbalance of the central nervous system, impairment of the baroreceptors, enhanced sympathetic activity, stimulation of the renin-angio-tensin-aldosterone system, increased cortisol levels, increased vascular reactivity due to increase in intracel-lular calcium levels, stimulation of the endothelium to release vasoconstrictors and loss of relaxation due to inflammation and oxidative injury of the endothelium leading to inhibition of endothelium-dependent nitric oxide production. Loss of relaxation due to inflamma-tion and oxidative injury of the endothelium by angio-tensin II leading to inhibition of endothelium-dependent nitric oxide production is the major contributors of the alcohol-induced hypertension. For the prevention of alcohol-induced hypertension is to reduce the amount of alcohol intake. Physical conditioning/exercise trainingis one of the most important strategies to prevent/treat chronic alcohol-induced hypertension on physiological basis. The efficacious pharmacologic treatment includes the angiotensin-converting enzyme(ACE) inhibitors or angiotensin Ⅱ type 1 receptor blockers(ARBs) which have antioxidant activity and calcium channel blockers. The most effective prevention and treatment of alcohol-induced hypertension is physical exercise and the use of ACE inhibitors or ARBs in the
文摘Neurocysticercosis(NCC) is one of the seven neglected endemic zoonoses targeted by the World Health Organization.It is considered a common infection of the nervous system caused by the Tanenia solium and is known to be the primary cause of preventable epilepsy in many developing countries.NCC is commonly resulted by the ingestion of Tanenia solium eggs after consuming undercooked pork,or contaminated water.The parasite can grow in the brain and spinal cord within the nervous system,causing severe headache and seizures beside other pathological manifestations.Immigration and international travel to endemic countries has made this disease common in the United States.NCC can be diagnosed with computed tomography and magnetic resonance imaging of the brain.The treatment of the NCC including cysticidal drugs(eg.,albendazole and praziquantel),and neurosurgical procedure,depending upon a the situation.A patient of Asian origin came to our clinic with complaints of dizziness,headaches and episodes seizures for the past twelve years without proper diagnosis.The computed tomography and magnetic resonance imaging scans indicated multilobulated cystic mass in the brain with the suspicion of neurocysticercosis.
文摘Heart failure(HF), the number one cause of death in the western world, is caused by the insufficient performance of the heart leading to tissue underperfusion in response to an injury or insult. It comprises complex interactions between important neurohormonal mechanisms that try but ultimately fail to sustain cardiac output. The most prominent such mechanism is the sympathetic(adrenergic) nervous system(SNS), whose activity and outflow are greatly elevated in HF. SNS hyperactivity confers significant toxicity to the failing heart and markedly increases HF morbidity and mortality via excessive activation of adrenergic receptors, which are G protein-coupled receptors. Thus, ligand binding induces their coupling to heterotrimeric G proteins that transduce intracellular signals. G protein signaling is turned-off by the agonist-bound receptor phosphorylation courtesy of G protein-coupled receptor kinases(GRKs), followed by βarrestin binding, which prevents the GRK-phosphorylated receptor from further interaction with the G proteins and simultaneously leads it inside the cell(receptor sequestration). Recent evidence indicates that adrenal GRK2 and βarrestins can regulate adrenal catecholamine secretion, thereby modulating SNS activity in HF. The present review gives an account of all these studies on adrenal GRKs and βarrestins in HF and discusses the exciting new therapeutic possibilities for chronic HF offered by targeting these proteins pharmacologically.
