Promising new therapeutic treatments using the fatty acid amide hydrolase (FAAH) inhibitor can be used to relieve symptoms in a patient suffering from a variety of conditions, including but not ...limited to insomnia, anxiety, fibromyalgia, migraines, arthritis, and other chronic pain conditions. FAAH is responsible for breaking down anandamide, which is an endogenous agonist of the CB1 cannabinoid receptor and analgesic neurotransmitter. The FAAH protein contains a catalytic triad of Ser 241, Ser 217, Lys 142 embedded in its center. The FAAH monomer assumes a twisted 11 strand β‐sheet in the middle of the monomer and 24 α‐helices surrounding the β‐sheets. The Divine Savior Holy Angels MAPS (Modeling A Protein Story) Team modeled the catalytic domain of FAAH using 3D technology. Inhibitors of the FAAH molecules perform better through noncovalent interactions with the triad active site. The inhibitors stop FAAH activity through hydrophobic interactions that result from the active site changing its shape. Noncovalent and reversible inhibitors bring higher selectivity and less unwanted side effects than already studied covalent inhibitors. Non‐covalent FAAH inhibitors are currently in development as analgesics lacking the adverse effects of opioid‐based analgesics. Further studies are being conducted with selective and potent FAAH inhibitors in order to reduce neurological pain suppression, reduction of cancer cells, and increase feeling of motivation. Currently, the United States is in an opioid crisis that caused 100,000 deaths in the last year, which is why new treatments involving FAAH inhibitors prove promising because they reduce the extreme effects opioid‐based drugs present.
Computed tomography (CT) was used to explore if changes in muscle cross-sectional area and quality after anterior cruciate ligament (ACL) injury and reconstruction would be related to knee function. ...Fourteen females and 23 males (16-54years) underwent clinical tests, subjective questionnaires, and CT 1week before and 1year after ACL surgery with semitendinosus-gracilis (STG) graft and rehabilitation. Postoperatively, knee laxity was decreased and functional knee measures and subjective patient scores improved. The most obvious remaining deficit was the quadriceps atrophy, which was significantly larger if the right leg was injured. Right-leg injury also tended to cause larger compensatory hypertrophy of the combined knee flexor and tibial internal rotator muscles (preoperatively). The quadriceps atrophy was significantly correlated with the scores and functional tests, the latter also being related to the remaining size of the gracilis muscle. Biceps femoris hypertrophy and, in males only, semimembranosus hypertrophy was observed following the ACL reconstruction. The lack of semimembranosus hypertrophy in the women could, via tibial internal rotation torque deficit, contribute to the less favorable functional and subjective outcome recorded for the women. The results indicate that the quadriceps, the combined knee flexor/tibial internal rotator muscles, side of ACL injury, and sex are important to consider in rehabilitation after STG graft. PUBLICATION ABSTRACT
Computed tomography (CT) was used to explore if changes in muscle cross‐sectional area and quality after anterior cruciate ligament (ACL) injury and reconstruction would be related to knee function. ...Fourteen females and 23 males (16–54 years) underwent clinical tests, subjective questionnaires, and CT 1 week before and 1 year after ACL surgery with semitendinosus‐gracilis (STG) graft and rehabilitation. Postoperatively, knee laxity was decreased and functional knee measures and subjective patient scores improved. The most obvious remaining deficit was the quadriceps atrophy, which was significantly larger if the right leg was injured. Right‐leg injury also tended to cause larger compensatory hypertrophy of the combined knee flexor and tibial internal rotator muscles (preoperatively). The quadriceps atrophy was significantly correlated with the scores and functional tests, the latter also being related to the remaining size of the gracilis muscle. Biceps femoris hypertrophy and, in males only, semimembranosus hypertrophy was observed following the ACL reconstruction. The lack of semimembranosus hypertrophy in the women could, via tibial internal rotation torque deficit, contribute to the less favorable functional and subjective outcome recorded for the women. The results indicate that the quadriceps, the combined knee flexor/tibial internal rotator muscles, side of ACL injury, and sex are important to consider in rehabilitation after STG graft.
Congenital heart block (CHB) is a transplacentally acquired autoimmune disease associated with anti-Ro/SSA and anti-La/SSB maternal autoantibodies and is characterized primarily by atrioventricular ...(AV) block of the fetal heart. This study aims to investigate whether the T-type calcium channel subunit α1G may be a fetal target of maternal sera autoantibodies in CHB.
We demonstrate differential mRNA expression of the T-type calcium channel CACNA1G (α1G gene) in the AV junction of human fetal hearts compared to the apex (18-22.6 weeks gestation). Using human fetal hearts (20-22 wks gestation), our immunoprecipitation (IP), Western blot analysis and immunofluorescence (IF) staining results, taken together, demonstrate accessibility of the α1G epitope on the surfaces of cardiomyocytes as well as reactivity of maternal serum from CHB affected pregnancies to the α1G protein. By ELISA we demonstrated maternal sera reactivity to α1G was significantly higher in CHB maternal sera compared to controls, and reactivity was epitope mapped to a peptide designated as p305 (corresponding to aa305-319 of the extracellular loop linking transmembrane segments S5-S6 in α1G repeat I). Maternal sera from CHB affected pregnancies also reacted more weakly to the homologous region (7/15 amino acids conserved) of the α1H channel. Electrophysiology experiments with single-cell patch-clamp also demonstrated effects of CHB maternal sera on T-type current in mouse sinoatrial node (SAN) cells.
Taken together, these results indicate that CHB maternal sera antibodies readily target an extracellular epitope of α1G T-type calcium channels in human fetal cardiomyocytes. CHB maternal sera also show reactivity for α1H suggesting that autoantibodies can target multiple fetal targets.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Congenital heart block develops in fetuses of anti-Ro52 Ab-positive women. A recurrence rate of 20%, despite the persistence of maternal autoantibodies, indicates that there are additional, yet ...unidentified, factors critical for development of congenital heart block. In this study, we demonstrate that besides the maternal MHC controlling Ab specificity, fetal MHC-encoded genes influence fetal susceptibility to congenital heart block. Using MHC congenic rat strains, we show that heart block develops in rat pups of three strains carrying MHC haplotype RT1(av1) (DA, PVG.AV1, and LEW.AV1) after maternal Ro52 immunization, but not in LEW rats (RT1(l)). Different anti-Ro52 Ab fine specificities were generated in RT1(av1) versus RT1(l) animals. Maternal and fetal influence was determined in an F(2) cross between LEW.AV1 and LEW strains, which revealed higher susceptibility in RT1(l) than RT1(av1) pups once pathogenic Ro52 Abs were present. This was further confirmed in that RT1(l) pups more frequently developed heart block than RT1(av1) pups after passive transfer of RT1(av1) anti-Ro52 sera. Our findings show that generation of pathogenic Ro52 Abs is restricted by maternal MHC, whereas the fetal MHC locus regulates susceptibility and determines the fetal disease outcome in anti-Ro52-positive pregnancies.
CONTEXT
Early access to contraception may increase postpartum contraceptive use. However, little is known about women's experiences receiving their desired method at the first postpartum visit or how ...access is associated with use.
METHODS
In a 2014–2016 prospective cohort study of low‐income Texas women, data were collected from 685 individuals who desired a reversible contraceptive and discussed contraception with a provider at their first postpartum visit, usually within six weeks of birth. Women's experiences were captured using open‐ and closed‐ended survey questions. Thematic and multivariate logistic regression analyses were employed to examine contraceptive access and barriers, and method use at three months postpartum.
RESULTS
Twenty‐three percent of women received their desired method at the first postpartum visit; 11% a prescription for their desired pill, patch or ring; 8% a method (or prescription) other than that desired; and 58% no method. Among women who did not receive their desired method, 44% reported clinic‐level barriers (e.g., method unavailability or no same‐day provision), 26% provider‐level barriers (e.g., inaccurate contraceptive counseling) and 23% cost barriers. Women who used private practices were more likely than those who used public clinics to report availability and cost barriers (odds ratios, 6.4 and 2.7, respectively). Forty‐one percent of women who did not receive their desired method, compared with 86% of those who did, were using that method at three months postpartum.
CONCLUSION
Eliminating the various barriers that postpartum women face may improve their access to contraceptives. Further research is needed to improve the understanding of clinic‐ and provider‐level barriers.
Chronic diseases are increasing worldwide, and the complexity of disease management is putting new demands on safe healthcare. Telemonitoring technology has the potential to improve self-care ...management with the support of healthcare professionals for people with chronic diseases living at home. Patient safety threats related to telemonitoring and how they may affect patients' and healthcare professionals' sense of security need attention. This study aimed to explore patients' and healthcare professionals' experiences of safety and sense of security when using telemonitoring of chronic conditions at home.
Semi-structured interviews were conducted with twenty patients and nine healthcare professionals (nurses and physicians), recruited from four primary healthcare centers and one medical department in a region in southern Sweden using telemonitoring service for chronic conditions in home healthcare.
The main theme was that experiences of safety and a sense of security were intertwined and relied on patients´ and healthcare professionals´ mutual engagement in telemonitoring and managing symptoms together. Telemonitoring was perceived to increase symptom awareness and promote early detection of deterioration promoting patient safety. A sense of security emerged through having someone keeping track of symptoms and comprised aspects of availability, shared responsibility, technical confidence, and empowering patients in self-management. The meeting with technology changed healthcare professionals' work processes, and patients' daily routines, creating patient safety risks if combined with low health- and digital literacy and a naïve reliance on technology. Empowering patients' self-management ability and improving shared understanding of the patient's health status and symptom management were prerequisites for safe care and the patient´s sense of security.
Telemonitoring chronic conditions in the homecare context can promote a sense of security when care is co-created in a mutual understanding and responsibility. Attentiveness to the patient's health literacy, symptom management, and health-related safety behavior when using eHealth technology may enlighten and mitigate latent patient safety risks. A systems approach indicates that patient safety risks related to telemonitoring are not only associated with the patient's and healthcare professionals functioning and behavior or the human-technology interaction. Mitigating patient safety risks are likely also dependent on the complex management of home health and social care service.
Celotno besedilo
Dostopno za:
CEKLJ, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Purpose: This study evaluated perioperative variables to predict death in nonruptured and ruptured abdominal aortic aneurysm (AAA) surgery.
Methods: A consecutive review of all patients who underwent ...AAA surgery from January 1984 to December 1993 was carried out. Perioperative variables were analyzed with univariate and multivariate statistical models to predict mortality rates.
Results: Four hundred seventy-eight patients with nonruptured AAAs and 157 patients with ruptured AAAs were studied. In patients with nonruptured AAAs, the mortality rate was 3.8%. Using stepwise logistic regression analysis, independent predictors of death were perioperative myocardial infarction (odds ratio OR, 5.0;
p < 0.01), prolonged postoperative ventilation (OR, 4.0;
p < 0.01), history of peripheral vascular disease (OR, 2.9;
p < 0.01), preoperative renal dysfunction (OR, 2.7;
p < 0.01), and history of congestive heart failure (OR, 2.6;
p < 0.03). In patients with ruptured AAAs, the mortality rate was 46%. Analysis of preoperative variables using multivariate stepwise logistic regression found predictors of death to be preoperative unconsciousness (OR, 3.1;
p < 0.01), advanced age (OR, 1.9;
p < 0.01), and cardiac arrest (OR, 1.8;
p < 0.05). In patients who survived the initial surgery for ruptured AAA, a second stepwise logistic regression model found independent predictors for subsequent postoperative death to be coagulation disorder (OR, 7.9;
p < 0.01), ischemic colitis (OR, 6.4;
p < 0.01), inotropic support beyond 48 hours (OR, 4.8;
p < 0.01), delayed transport to operating room (OR, 4.6;
p < 0.01), advanced age (OR, 4.4;
p < 0.01), perioperative myocardial infarction (OR, 4.0;
p < 0.05) and postoperative renal dysfunction (OR, 3.7;
p < 0.01).
Conclusion: Prolonged ventilation, perioperative myocardial infarction, a history of peripheral vascular disease, preoperative renal dysfunction, and a history of congestive heart failure are independent predictors of perioperative death in patients with nonruptured AAAs. For patients with ruptured AAAs, mortality rates can be estimated before surgery using age, level of consciousness, and cardiac arrest. For patients who survive the initial surgery for ruptured AAA, subsequent mortality rates can also be predicted. (J Vasc Surg 1996;24:614-23.)
To delineate and clarify the meaning of the concept of self-care monitoring from a patient perspective.
A systematic search was performed in the databases ASSIA, CINAHL, PsycInfo, and PubMed (January ...2016-September 2021). A selection of 46 peer-reviewed articles was included in the study and analysed using Rodgers' Evolutionary Method for Concept Analysis.
The following four attributes were identified: Tracking symptoms, signs, and actions, Paying attention, Being confident, and Needing routines, creating a descriptive definition: "Self-care monitoring is an activity that means a person has to pay attention and be confident and needs routines for tracking symptoms, signs, and action." The antecedents of the concept were shown to be Increased knowledge, Wish for independence, and Commitment. The concepts' consequences were identified as Increased interaction, Perceived burden, and Enhanced well-being.
This concept analysis provides extensive understanding of self-care monitoring from a patient perspective. It was shown that the concept occurs when a person practices self-care monitoring at home either with or without devices. A descriptive definition was constructed and presented with exemplars to encourage practice of the concept in various healthcare settings and could be of relevance to people with chronic illnesses or other long-term conditions.
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