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Agitation, a common dementia symptom often arising from untreated pain, lacks comprehensive research on its connection with opioids prescribed for long-term pain. This study investigated the relationship between opioid use and agitation in dementia patients. Participants ( n  = 188) were categorized into opioid, acetaminophen PRN, or no-pain medication groups. Despite higher reported pain levels in the opioid group, no significant differences in agitation were observed among the groups. In conclusion, opioid use for pain management in older adults with dementia did not significantly impact agitation, emphasizing the ongoing importance of proper pain management in improving dementia care and addressing agitation in this population., Competing Interests: The authors have no conflict of interest to report., (© 2024 – The authors. Published by IOS Press.)

Background: Quality of life (QoL) is an important outcome to capture in clinical trials evaluating deprescribing interventions., Objective: We aimed to conduct a scoping review to examine how QoL has been measured in deprescribing trials among older people and identify potentially relevant QoL scales, to better inform QoL measurement in future deprescribing trials., Methods: We searched MEDLINE, Embase, PsycINFO, the Cochrane Central Register of Controlled Trials, Google Scholar, Epistemonikos, ClinicalTrials.gov, and reference lists of eligible studies (from inception to October 2023). We included randomized and non-randomized comparative studies with a control group that evaluated deprescribing and polypharmacy reduction interventions in people ≥ 65 years of age and measured QoL as an outcome. We also included studies describing the development and validation of QoL scales related to deprescribing, polypharmacy, or medication burden in adults ≥ 18 years of age. Two independent reviewers screened titles and abstracts, then full texts. Two independent reviewers extracted data from 25% of eligible studies in order to verify agreement, then a single reviewer extracted data from the remaining studies, which a second reviewer cross-checked. We critically appraised scales based on the COSMIN checklist., Results: We retrieved 7290 articles, of which 52 were eligible for inclusion, including 44 deprescribing trials and eight scale development studies. From these studies, we found 21 scales that have been used in the context of deprescribing/polypharmacy (12 generic scales used in clinical trials and nine medication-specific scales). Variations of the generic EQ-5D were the most used scales. The measurement properties of scales for capturing changes in QoL from deprescribing were uncertain. Medication-specific QoL scales have not been employed in deprescribing clinical trials and thus, their performance in this context is also not clear., Conclusions: Several existing QoL scales have been applied to the context of deprescribing/polypharmacy clinical trials, and new scales specific to the problem have been proposed. If deprescribing does impact QoL, our findings suggest it is uncertain whether existing QoL scales can practically and reliably capture such a change or whether any scale is best. However, this review compares various aspects of the scales that researchers and clinicians can consider in decisions about measuring QoL in deprescribing trials, and in planning future research., Protocol Registration: Open Science Framework: osf.io/aez6w., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Auricular reconstruction remains a challenging procedure, requiring a high degree of manual dexterity and attention to detail in order to reconstruct the complex three-dimensional geometry of the ear successfully. Most techniques will rely on autologous cartilage for auricular framework fabrication, carrying a risk of donor and recipient site morbidity. The aim of this report is to investigate the complications and aesthetic outcomes associated with autologous cartilage harvest in auricular reconstruction. A systematic review protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO) and reported in accordance with the Preferred Reporting for Items for Systematic Reviews and Meta-Analyses. Comprehensive electronic search strategies for four databases were developed. Studies were screened according to the inclusion and exclusion criteria by two independent reviewers. The literature search identified 7171 articles. Filtering for relevance and duplication reduced the number of articles to 52. A total of 12,215 patients underwent auricular reconstruction utilising autologous cartilage. Indications included 11,696 patients due to microtia, 334 patients due to burns or trauma, 70 patients due to constricted ears, and 115 patients due to prominent ears. The most commonly reported donor site complications included chest wall deformities (n = 159). The most commonly reported recipient site complications included hypertrophic or keloid scars (n = 279), haematoma (n = 155), tissue expander exposure (n = 111), cartilage or framework exposure (n = 122), and cartilage framework deformation or resorption (n = 50). Although a challenging procedure, auricular reconstruction utilising autologous cartilage is possible. Exceptional aesthetic results can be achieved when performed by a skilled surgeon on appropriately selected individuals. However, the potential risks and complications associated with the procedure should be discussed with the patient and family beforehand., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Abukhder et al.)

Background: Diffuse sclerosing osteomyelitis (DSO) affecting the mandible is an uncommon condition characterised by recurrent pain and functional disturbances. Traditional treatments involving antibiotics, steroids, and analgesics have generally yielded unsatisfactory results. Numerous articles have proposed the utilisation of bisphosphonate therapy as an alternative approach to achieve sustained symptom relief. This study aims to consolidate the available evidence on the effectiveness of bisphosphonate therapy in managing DSO., Methods: A systematic review protocol was registered with PROSPERO and reported in accordance with the Preferred Reporting for Items for Systematic Reviews and Meta-Analyses. Comprehensive electronic search strategies were devised, and studies were screened based on predefined inclusion and exclusion criteria., Results: Ten articles met the eligibility criteria, encompassing a total of 135 patients diagnosed with DSO who received bisphosphonate treatment. All included studies consistently reported a reduction in pain levels and swelling, along with a decrease in the cumulative use of analgesics. The majority of patients reported long-lasting symptom improvement with bisphosphonate therapy. Notably, four studies documented improvements in maximal mouth opening, with one study reporting a mean increase of 9.6mm. Furthermore, six studies observed improvements in panoramic radiographs and cone beam computed tomography scans, with one publication describing two patients exhibiting near-normal bone architecture. Importantly, all studies reported the absence of long-term complications., Conclusions: Bisphosphonate therapy emerges as a promising treatment modality for DSO, exhibiting efficacy in symptom alleviation and radiological enhancement while conferring lasting benefits. Nevertheless, further prospective studies are warranted to refine treatment protocols and substantiate these findings., Competing Interests: None.Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: Patients and physicians in low- and middle-income countries (LMICs) face challenges owing to limited expertise and suboptimal access to appropriate diagnostic and treatment modalities. We report our experience in treating posterior fossa ependymoma (PFE) at MAHAK, a charity organization in Iran whose radiation oncology department is the only one exclusively dedicated to childhood cancer in the whole country., Methods and Materials: Pediatric patients with PFE referred to MAHAK between November 2008 and January 2016 were identified. Details on investigations and management done before referral were collected. Management at MAHAK and patient outcomes were analyzed., Results: Of 80 patients diagnosed as having ependymoma, 54 with PFE were identified. Forty-three patients received adjuvant radiation therapy, and 11 were irradiated initially after recurrence. At a median follow-up of 5.1 years (range, 0.3-9.7 years), the latter group had the worst outcome, with a 5-year overall survival (OS) rate of 27% (95% CI, 7%-54%). Patients who started radiation therapy within 77 days after initial surgery had a better outcome compared with those who started later (5-year OS: 74% vs 32%; P = .05). Compliance with follow-up recommendations was poor. Only 22% of the patients had at least 2 IQ test assessments, and 50% showed some decline over time. Three cases of growth hormone deficiency were detected, but none of the patients received replacement therapy., Conclusions: Access to pediatric neurosurgery, anesthesia, and timely radiation therapy are among the most challenging obstacles to be overcome in LMICs. Our series confirmed that chemotherapy is not an appropriate option for delaying radiation therapy, especially in young children. The importance of long-term follow-up should be acknowledged by the parents and medical team., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The limitations of current cancer therapies, including the increasing prevalence of multidrug resistance, underscore the urgency for more effective treatments. One promising avenue lies in the repurposing of existing drugs. This review explores the impact of phenothiazines, primarily used as antipsychotic agents, on key mechanisms driving tumor growth and metastasis. The cationic and amphiphilic nature of phenothiazines allows interaction with the lipid bilayer of cellular membranes, resulting in alterations in lipid composition, modulation of calcium channels, fluidity, thinning, and integrity of the plasma membrane. This is especially significant in the setting of increased metabolic activity, a higher proliferative rate, and the invasiveness of cancer cells, which often rely on plasma membrane repair. Therefore, properties of phenothiazines such as compromising plasma membrane integrity and repair, disturbing calcium regulation, inducing cytosolic K-RAS accumulation, and sphingomyelin accumulation in the plasma membrane might counteract multidrug resistance by sensitizing cancer cells to membrane damage and chemotherapy. This review outlines a comprehensive overview of the mechanisms driving the anticancer activities of phenothiazines derivates such as trifluoperazine, prochlorperazine, chlorpromazine, promethazine, thioridazine, and fluphenazine. The repurposing potential of phenothiazines paves the way for novel approaches to improve future cancer treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Mehrabi, Elmi and Nylandsted.)

Introduction: Subacute thyroiditis (SAT), also known as de Quatrain's thyroiditis or granulomatous thyroiditis, is an inflammatory disease of the thyroid. Most of the time, it manifests in the thirties to fifties and is more common in women. SAT can have either viral or post-viral origin. Some viruses, like influenza, COVID-19, Epstein-Barr virus, cytomegalovirus, hepatitis, coxsackievirus 16, and mumps virus, have been linked to SAT development. The COVID-19 pandemic has affected people's lives all around the world and has changed our attitude toward the treatment of many diseases. It has also made us look deeper into the subject in a way that we would be able to treat this sort of disease with a newer insight., Objective: Regarding the importance of this issue, we decided to summarize our extensive searches from online databases, including PubMed, Google Scholar, Medline, Web of Science, and Scopus until February 2023, which we found effective in elucidating the association of subacute thyroiditis and viral diseases., Method: Different online databases were searched for narrative review articles, systemic review articles, and original articles, which were published until February 2023., Result: According to the included studies, we found that there is a correlation between SAT and several viruses such as Epstein-Barr virus, influenza virus, human immunodeficiency virus, cytomegalovirus, oral and cervical virus, hepatitis, dengue virus, and SARS-COV-2. The effect of each of the viral diseases mentioned in the SAT is given in the text., Conclusions: According to the results mentioned in the text, because SAT may be challenging for early diagnosis, due to the potential of classic symptoms as well as the interference of similar clinical symptoms between thyrotoxicosis and viral reactions, the correlation between SAT and viral diseases should be considered so that we can avoid misdiagnosis and lateness., Competing Interests: Authors declare no conflict of interest., (National Institute of Public Health NIH – National Research Institute.)

Telephone practice is an essential component of ambulatory nursing practice to address patient concerns between their clinic visits. Proactive telephone practice has been part of oncology nursing at a large regional cancer centre for six years and involves taking the initiative of calling patients and families before they are in distress. A review of nursing practice regarding proactive calls in the centre revealed a lack of standardization across cancer disease sites in identifying and assessing patients who would benefit from proactive calls, and variability in how nurses documented telephone interactions. To create a standardized approach for proactive telephone practice, we began by identifying when patients require a proactive call based on key transition points across their cancer care trajectory. Based on the practice review of proactive calls, the needs assessment with patients, and a literature review, a Proactive Telephone Nursing Assessment Guideline was developed. The guideline provided guidance for conducting a proactive telephone call and identifying patient needs, intervening as required, and documenting the exchange. The guideline was piloted with newly diagnosed patients to determine if the call helped in meeting their needs. Informational and practical needs were most common. The pilot revealed both patients and families were satisfied with the proactive call. Nurses felt the guideline was useful, but could be burdensome, especially when it was first used. Through the pilot, it was identified that proactive telephone calls can be utilized to focus on patient and family supportive care needs., (© 2023 Canadian Association of Nurses in Oncology (CANO).)

Telepractice in oncology is an evolving practice for nurses and cancer patients. Understanding the needs of our patients led the nursing leaders of a large academic teaching centre to undertake the challenge of creating a measurable and sustainable Telephone Readiness Assessment and Orientation Program. The experiences of patients and families regarding telephone interactions triggered the launch of Live Voice Answer, a centre-wide telepractice change. To support the transition from clinic practice to telepractice with the introduction of Live Voice Answer, an orientation program was created to lay the foundation for nurses to provide excellent standardized telepractice care. A Practice Training Process map was designed to depict three stages required to successfully complete the orientation: Telephone Readiness Assessment, Telephone Practice Training session, and Practical Application. The frameworks used to support the Practice Training Process includes COSTaRS, College of Nurses of Ontario Practice Guideline: Telepractice, Cancer Care Ontario: Oncology Nursing Telepractice Standard, Cancer Care Ontario - Symptom Management Guides as well as our organizational policies. Benner's Novice to Expert Theory is also embedded to guide the skill/competency development. The purpose of this manuscript is to describe the telephone practice orientation program and share lessons learned that have contributed to its current evolution., (© 2022 Canadian Association of Nurses in Oncology (CANO).)

In 2016, a Live Voice Answer symptom management and distress telephone line was developed at a large regional cancer centre in Toronto. Prior to the initiation of Live Voice Answer, the previous telephone practice involved patients leaving a voicemail message for a nurse without a definitive return call time. An interprofessional team, including patient partners, sought to address this drawback and ensure all patients living with cancer have access to a nurse in real time (live voice) when they called the centre. After piloting the feasibility of real time telephone access, the Live Voice Answer initiative expanded beyond the pilot to meet the needs of all patients and families. Overall, the Live Voice Answer initiative has led to marked improvements in patient satisfaction compared to the pre-pilot state and timeliness of telephone access for patients and their families. This article describes the Live Voice Answer initiative, process improvements, and evaluation results., (© 2022 Canadian Association of Nurses in Oncology (CANO).)

Objectives: Neuropsychiatric symptoms (NPSs) in those with major neurocognitive disorder (MNCD) include the responsive behaviors of agitation and aggression. Electroconvulsive therapy (ECT) has shown some effectiveness based on retrospective studies and one open label prospective study. We hypothesized that ECT will reduce NPSs between baseline and after treatment in those with medication-refractory behaviors., Method/design: This Canadian prospective multicenter study included MNCD patients admitted to geriatric psychiatry units for the management of refractory NPSs. All treatment-refractory participants suffered from advanced MNCD. We conducted the Neuropsychiatric Inventory-Clinician version and the Pittsburgh Agitation Scale at baseline, and during and after the ECT course. A bitemporal or bifrontal ECT series based on dose titration to 1.5 to 2.5 times seizure threshold was administered., Results: Data were collected for 33 patients with a mean age of 73 and categorized with severe MNCD using the Functional Assessment Staging of Alzheimer's Disease scale (stages 6 and 7). The data showed a drop in mean Neuropsychiatric Inventory-Clinician version from 58.36 to 24.58 (P < 0.0001). Mean Neuropsychiatric Inventory agitation subscale dropped from 7.12 to 3.09 (P = 0.007). Mean Neuropsychiatric Inventory aggression subscale dropped from 6.94 to 0.97 (P < 0.0001). There was a concomitant significant decline in Pittsburgh Agitation Scale scores. No participants dropped out because of intolerance of ECT. One participant died from pneumonia, which did not appear related to ECT., Conclusions: In this naturalistic study, ECT was found to be a safe and effective treatment for certain NPSs in people with MNCD. This can translate into improving quality of life., Competing Interests: P.C. is a coowner of Brainstim (rTMS) Healthcare, advisory board for Janssen-Ortho. The remaining authors have no conflicts of interest or financial disclosures to report., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Nurses play a key role in increasing the efficiency of healthcare systems. Given the 24-hour performance of hospitals and the small number of nurses in the field of treatment, it is quintessential to re-shift them in the hospital. This study set out to achieve coherence in nursing shift planning and justice in the order of shifts in hospital., Methods: This applied and a developmental study was performed from 2019 to 2020. We used genetic algorithm to provide operational solutions and define flexible shifts and plan nurses' working hours in Yas Hospital, Tehran University of Medical Sciences Hospital, Tehran, Iran., Results: Based on the selection of each nurse and determining the approved shifts of each ward, the possibility of appropriate planning was provided to determine the required shifts per month and to estimate the needs of each department., Conclusion: Using genetic algorithm and nursing shift in office automation console provides useful tools for managers at all organizational levels, according to which a good balance between the hospital's need for nurse and nurses' demands in different time periods., Competing Interests: Conflict of interest The authors declare that there is no conflict of interest., (Copyright © 2022 Torabi et al. Published by Tehran University of Medical Sciences.)

Background: Agitation and aggression are common in patients with Alzheimer's disease and related dementias and pose a significant burden on patients, caregivers, and the healthcare systems. Guidelines recommend personalized behavioral interventions as the first-line treatment; however, these interventions are often underutilized. The Standardizing Care for Neuropsychiatric Symptoms and Quality of Life in Dementia (StaN) study (ClinicalTrials.gov Identifier # NCT0367220) is a multisite randomized controlled trial comparing an Integrated Care Pathway, that includes a sequential pharmacological algorithm and structured behavioral interventions, with treatment-as-usual to treat agitation in dementia in long-term care and inpatient settings., Objective: To describe the rationale and design of structured behavioral interventions in the StaN study., Methods: Structured behavioral interventions are designed and implemented based on the following considerations: 1) personalization, 2) evidence base, 3) dose and duration, 4) measurement-based care, and 5) environmental factors and feasibility., Results: The process to design behavioral interventions for each individual starts with a comprehensive assessment, followed by personalized, evidence-based interventions delivered in a standardized manner with ongoing monitoring of global clinical status. Measurement-based care is used to tailor the interventions and integrate them with pharmacotherapy., Conclusion: Individualized behavioral interventions in patients with dementia may be challenging to design and implement. Here we describe a process to design and implement individualized and structured behavioral interventions in the context of a multisite trial in long-term care and inpatient settings. This process can inform the design of behavioral interventions in future trials and in clinical settings for the treatment of agitation in dementia.

The identification of biological markers for psychosis has an impact on its diagnosis, prognosis, and likelihood of treatment response. Tissue plasminogen activator (tPA) is involved in important functions such as synaptic plasticity, long-term potentiation and neurogenesis. Plasminogen activator inhibitor (PAI-1) is the most important inhibitor of tPA. Preliminary studies have shown that schizophrenia patients have lower tPA and higher PAI-1 levels than the general population. The association of tPA and PAI-1 abnormalities with psychotic spectrum disorders, however, remains elusive. Our primary objective was to assess the plasma levels of tPA and PAI-1 in patients experiencing acute psychotic episodes as compared to those in healthy controls. In this prospective case-control study, we collected peripheral blood samples from psychiatric inpatients and healthy age, gender and race-matched subjects and determined plasma levels of tPA and PAI-1 by enzyme-linked immune-absorbent assays. Plasma levels of PAI-1 in patients with schizoaffective disorder were significantly lower as compared to those in control subjects (P = 0.03). tPA was lower in cases as compared to controls although it did not reach statistical significance. Asian patients and controls had lower PAI-1 levels. Further, Asian patients with schizoaffective disorder had significantly lower PAI-1 level compared to Asian patients with schizophrenia. Our results indicate that patients with schizoaffective disorder have lower PAI-1 levels than those with schizophrenia, affective psychosis, and healthy controls. Further studies are warranted to explore the potential of PAI-1 as a biomarker for diagnosing schizoaffective disorder., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: The practice environment pivotal role in patients and nurses better outcomes is evident. Practice Environment Scale of Nursing Work Index (PES-NWI) is widely utilized to assess nursing work environments. The present study was conducted to demonstrate the validity and reliability of the Persian version of PES-NWI., Materials and Methods: The instrument was translated and its psychometrics were investigated by content, construct validity (factor analysis), and homogeneity (internal consistency and intraclass correlation) on a sample of 350 nurses at educational hospitals in East Azerbaijan, Iran., Results: The 30 items loaded onto 4 factors explained 34.95-50.06% of the variance. The items across the factors differed slightly from those reported by the original author of the PES-NWI. Cronbach's alpha and Pearson coefficient for the entire instrument and also for extracted factors was 0.70-0.96., Conclusions: The Persian version of PES-NWI has an appropriate level of validity and reliability in the Iranian setting for nurses. The subscale of Nursing Foundations for quality care needs modification., Competing Interests: There are no conflicts of interest.

Background: Acute lymphoblastic leukemia (ALL) and non-Hodgkin's lymphoma (NHL) are the most common malignancies in children and adolescents. Therapies such as corticosteroids, cytotoxic and radiotherapy will have harmful effect on bone mineral density (BMD) which can lead to increased possibility of osteoporosis and pathological fractures., Subjects and Methods: This 3-year cross-sectional study was performed in 50 children with ALL (n=25) and NHL (n=25) at Dr. Sheikh Children's Hospital in Mashhad. Half the patients received chemotherapy alone (n=25), while the other half received chemotherapy plus radiotherapy (n=25). We assessed them in the remission phase by DEXA bone mineral densitometry at the lumbar spine and femoral neck (hip). The survey results were adjusted in accordance with age, height, sex and Body Mass Index. Results : The mean age was 3.93± 8.28 years. There was no significant difference in bone biomarkers (Ca, P, ALP, PTH) among ALL, NHL and also the two treatment groups. Children with ALL had lower density at the hip and lumbar spine (p-value<0.001 and p-value=0.018, respectively). Among the total of 50 patients, 3 patients had normal results for detected hip BMD (6%), while 14 (28%) had osteopenia and 33 had osteoporosis (66%). Only one patient had normal BMD among all the patients who received chemotherapy plus radiotherapy, whereas 2 patients had normal BMD with just chemotherapy treatment. Conclusion : Given that 94% of our patients had abnormal bone density, it seems to be crucial to pay more attention to the metabolic status and BMD in children with cancer.

Objective: In chronically ill children who are hospitalized, many mood changes occur. For example, in children with cancer or renal failure, prolonged hospitalization and chemotherapy can lead to depression. With the improved survival of childhood malignancies, the effect of treatment on child's psychosocial well-being becomes increasingly relevant. In this study, we examined the prevalence of depression in hospitalized children with chronic and acute conditions in Dr Sheikh Pediatrics Hospital in Mashhad., Materials & Methods: After receiving the approval from the Ethics Committee of Mashhad University of Medical Sciences, we did this cross-sectional descriptive study, from April to June 2012 in Dr Sheikh Pediatric Hospital in Mashhad. Ninety children, between 8 to 16 years, were screened for depression. The sampling method was census. Children with a history of depressive or other mental disorders were excluded. Three groups of children (children with chronic renal disease, malignancy, and acute disease) were evaluated for depression using standard Children Depression Inventory Questionnaire (CDI). Two specifically trained nurses filled out the questionnaires at patients' bedside under the supervision of a psychiatrist. Depression scores were then analyzed by SPSS software., Results: Of 90 children, 43(47.7%) were male and 47(52.2%) were female. The Children's mean age was 11±2.3 years, and the mean length of hospitalization was 8±5.3 days. Depression was detected in various degrees in 63% of patients (N=57), and 36.6% of children (N=32) had no symptoms of depression. Severe depression was not seen in any of the patients with acute illness. More than half of patients with cancer and chronic kidney disease had moderate to severe depression. There was a significant statistical relationship between the duration of illness and severity of depression. There was also a significant correlation between severity of depression and frequency of hospitalization. Children who had been hospitalized more than 3 times in the previous year, experienced more severe levels of depression. We also found a significant correlation between pubertal age and severity of depression in patients with cancers and chronic renal failure., Conclusion: Children who are hospitalized due to chronic conditions are at a higher risk for mood disorders in comparison with the ones with acute conditions. It is therefore advisable to consider more practical plans to improve the care for hospitalized children's mental health.

Purpose: The purpose was twofold: (1) to develop a comprehensive profile of patients discharged from an inpatient oncology rehabilitation unit and (2) to explore the relationships between patient characteristics and functional status., Methods: A retrospective review of electronic data from all patients discharged from oncology rehabilitation between November 1, 2008, and March 31, 2010, was conducted. Data elements included age, sex, primary language, living arrangements, cancer diagnosis, comorbidities, and admission and discharge Functional Independence Measure (FIM(™)) scores. Descriptive statistics were compiled for all data elements. General linear regression was conducted to determine the descriptors independently associated with FIM(™) discharge and FIM(™) change scores., Results: There were 153 eligible records. The patients' age ranged from 38 to 97 years (M = 72.6, SD = 12.9); 59.5% were women, and 39.3% lived alone prior to hospitalization. The most common diagnoses were colorectal cancer (n = 45, 28.8%), metastatic disease (n = 24, 15.7%), and cancer of the urinary organs (n = 14, 9.2%). Service goals were met for 77.1%. Patients improved an average of 17.1 (SD = 8.8) points on the FIM(™). Being older and having a diagnosis of brain or uterine cancer were associated with lower FIM™ change scores., Conclusions: In this sample, the majority of patients were older women, and many lived alone. While the group as a whole made significant functional gains, those who were younger improved more. Having a diagnosis of uterine or brain cancer was associated with lower functional change scores. This study was limited by a small sample size and the retrospective design; however, the results provide a foundation for future prospective research.

The study was designed to evaluate the effects of diethyldithiocarbamate (DDC), an superoxide dismutase (SOD) blocker on endothelial function in db/db mice. The db/db and wild-type (WT) mice were randomly divided into low intensity exercise, moderate intensity exercise and control (sedentary) groups. Mice were exercised daily, 5 days per week. After 6 weeks, ring segments of aortae were mounted in wire myograph and acetylcholine (ACh) concentration response curves were recorded in absence or presence of DDC and DDC plus SOD. Results showed that ACh concentration response curve was similar in WT and WT exercised groups. Incubation of aorta rings of WT mice with DDC suppressed the maximum ACh response (p<0.05). Subsequent incubation with SOD restored vasodilatory response in WT mice. The vasodilatation to ACh was significantly reduced in sedentary db/db mice compare to WT (p<0.05) and incubation with DDC did not further decrease this response, however, addition of SOD restored the vasodilatation to ACh to that observed in WT mice. Mild and moderate exercised db/db mice had ACh response similar to that in WT mice. Incubation with DDC incubation reduced ACh induced vasodilatation and addition of SOD restored this response. Our results support the conclusion that SOD mimetics can be used to improve superoxide-mediated endothelial dysfunction in diabetic db/db mice.

Regulation of coronary function in diabetic hearts is an important component in preventing ischemic cardiac events but remains poorly studied. Exercise is recommended in the management of diabetes, but its effects on diabetic coronary function are relatively unknown. We investigated coronary artery myogenic tone and endothelial function, essential elements in maintaining vascular fluid dynamics in the myocardium. We hypothesized that exercise reduces pressure-induced myogenic constriction of coronary arteries while improving endothelial function in db/db mice, a model of type 2 diabetes. We used pressurized mouse coronary arteries isolated from hearts of control and db/db mice that were sedentary or exercised for 1 h/day on a motorized exercise-wheel system (set at 5.2 m/day, 5 days/wk). Exercise caused a approximately 10% weight loss in db/db mice and decreased whole body oxidative stress, as measured by plasma 8-isoprostane levels, but failed to improve hyperglycemia or plasma insulin levels. Exercise did not alter myogenic regulation of arterial diameter stimulated by increased transmural pressure, nor did it alter smooth muscle responses to U-46619 (a thromboxane agonist) or sodium nitroprusside (an endothelium-independent dilator). Moderate levels of exercise restored ACh-simulated, endothelium-dependent coronary artery vasodilation in db/db mice and increased expression of Mn SOD and decreased nitrotyrosine levels in hearts of db/db mice. We conclude that the vascular benefits of moderate levels of exercise were independent of changes in myogenic tone or hyperglycemic status and primarily involved increased nitric oxide bioavailability in the coronary microcirculation.

Aims/hypothesis: Exercise ameliorates oxidative stress-mediated diabetic vascular endothelial dysfunction through poorly defined mechanisms. We hypothesised that, in addition to improving metabolic parameters, upregulation of antioxidants such as superoxide dismutase (SOD) mediates exercise-induced reductions of oxidative stress and increased nitric oxide (NO) bioavailability, and also restores vasodilatation., Methods: Type 2 diabetic db/db and normoglycaemic wild-type mice were exercised at moderate intensity for 1 h a day for 7 weeks, leading to a 10% body weight loss. Sedentary animals or those undergoing a low-intensity exercise regimen causing non-significant weight loss were also used. We examined aortic endothelial cell function, NO bioavailability and various biomarkers of oxidative stress., Results: Moderate-intensity exercise lowered body weight, increased mitochondrial manganese SOD (MnSOD) and both total and phosphorylated (Ser1177) endothelial nitric oxide synthase (eNOS) protein production; it also reduced whole-body (plasma 8-isoprostane) and tissue oxidative stress (nitrotyrosine immunostaining or protein carbonyl levels in the aorta). Low-intensity exercise did not alter body weight; however, it upregulated cytosolic Cu/Zn-SOD instead of MnSOD, and still demonstrated all the above benefits in the db/db aorta. Importantly, both exercise protocols improved endothelial-dependent vasodilatation and NO bioavailability without altering hyperglycaemic status in db/db mice., Conclusions/interpretation: Exercise reverses diabetic vascular endothelial dysfunction independently of improvements in body weight or hyperglycaemia. Our data suggest that upregulation of eNOS and specific SOD isoforms could play important roles in improving NO bioavailability, as well as in reversing endothelial dysfunction in type 2 diabetes patients through lifestyle modifications in the management of diabetes.

Vascular dysfunction is linked with increased free radical generation and is a major contributor to the high mortality rates observed in diabetes. Several probable sources of free radical generation have been suggested in diabetes, including cytochrome P450 (CYP) monooxygenase-dependent pathways. CYP-mediated superoxide production reduces nitric oxide (NO) bioavailability. In this study, we focus on the contribution of monooxygenase enzyme-generated reactive oxygen species in vascular dysfunction in an experimental model of diabetes mellitus type II. Diabetic male mice (db/db strain) and their age-matched controls received daily intraperitoneal injections of either the CYP 2C inhibitor sulfaphenazole (5.13 mg/kg) or saline (vehicle control) for 8 weeks. Although sulfaphenazole did not change endothelium-dependent vasodilation in control mice, it restored endothelium-mediated relaxation in db/db mice. We report for the first time that CYP 2C inhibition reduces oxidative stress (measured as plasma levels of 8-isoprostane), increases NO bioavailability (measured as NO(2)(-)) and restores endothelial function in db/db mice without affecting plasma glucose levels. Based on our findings, we speculate that inhibition of free radical generating CYP 450 monooxygenase enzymes restores endothelium-dependent vasodilation to acetylcholine. In addition, it reduces oxidative stress and increases NO bioavailability.

Paraquat (PQ) is a highly toxic herbicide that is used in most of the countries without restriction. The cytotoxic effect of PQ is mediated by radicals, which are the products of PQ reduction in cells. The anti-oxidative action of captopril, an angiotensin-converting enzyme inhibitor, appears to be through its ability to scavenge reactive oxygen species. In this study, the heptoprotective effect of captopril against PQ-induced hepatotoxicity was evaluated using primary cultured rat hepatocytes. Hepatocytes were isolated from male Wistar rats using a two-step collagenase perfusion, following incubation in the presence of captopril at 0.1, 0.2, 0.4 and 0.8 mM with or without PQ (5 mM). Hepatoprotective effects of captopril were studied indicating glutathione level intensity, thiobarbituric acid reactive substances (TBARs) formation, lactate dehydrogenase (LDH) leakage and cell viability every 70 min for 210 min. Captopril at 0.2 mM concentration maintained the LDH leakage, glutathione level and cell viability in the presence of 5 mM PQ. In spite of a significant elevation in TBARs formation in the PQ group, captopril did not show any significant protection. In conclusion, our data reveals that incubation of freshly isolated rat hepa-tocytes with captopril (0.2 mM) significantly protected the hepatocytes against the cytotoxicity of PQ (P < 0.05).

Metalloproteins are proteins capable of binding one or more metal ions, which are often required for their biological function or for regulation of their activities or for structural purposes. In high-throughput genome-level protein investigation efforts, such as Structural Genomics, the systematic experimental characterization of metal-binding properties (i.e. the investigation of the metalloproteome) is not always pursued, and remains far from trivial. In the present work we have applied a bioinformatic approach to investigate the occurrence of (putative) non-heme iron-binding proteins in 57 different organisms spanning the entire tree of life. It is found that the non-heme iron-proteome constitutes between 1% and 10% of the entire proteome of an organism. However, the iron-proteome constitutes a higher fraction of the proteome in archaea (on average 7.1% +/- 2.1%) than in bacteria (3.9% +/- 1.6%) and in eukaryota (1.1% +/- 0.4%). The analysis of the function of each putative iron-protein identified suggests that extant organisms have inherited the large majority of their iron-proteome from the last common ancestor., ((c) 2007 Wiley-Liss, Inc.)

The effect of chronic cigarette smoking on endothelin modulation of vascular contraction, and CYP enzyme levels was studied in 20 male Sprague-Dawley rats. The animals were divided equally into smoking and non-smoking groups. The smoking group was exposed to 6 research cigarettes per rat per day 5 days a week for 16 weeks. The control group was sham smoked. Functional contractile studies were performed in aortas and carotid arteries to determine the regulation of vascular tone by basal release of endothelin. Liver samples were analyzed for CYP1A1 and CYP1A2 gene expression by RT-PCR. Plasma samples were assessed for endothelin-1 (ET-1) level by enzyme immuno assay (EIA). Treatment of aortas and carotid arteries with bosentan, the dual endothelin receptor antagonist, caused a significant reduction in constrictor responses of smoking rats, indicating, increase greater regulation of tone by endothelin in smoker rats compared to controls. There was a greater expression of the cytochrome P450-liver enzymes (CYP1A1 and CYP1A2) in smoker rats. Body weight gain was also significantly decreased in smoker rats. We conclude that increased endothelin release in smoker rats significantly contributes to increased arterial tone and so contribute to the cardiovascular pathophysiology associated with cigarette smoking, such as increased vascular muscularization, increased contraction, decreased dilation and possibly vasospasm.

Aerial parts of Swertia longifolia Boiss. (Gentianaceae), which grows in the north of Iran, were screened for hepatoprotective activity against paracetamol (acetaminophen)-induced hepatotoxicity in Swiss mice. Pretreatment with total plant extract and swerchirin, the major component of the plant, significantly reduced the elevation of biochemical parameters, AST (aspartate aminotransferase), ALT (alanine aminotransferase) and ALP (alkaline phosphatase), the enzymes that are increased by liver damage (P < 0.001). Our results indicated that total plant extract and swerchirin were hepatoprotective in the range of 6-50 mg kg(-1) orally.

The "A Disintegrin And Metalloproteinase" (ADAM) protein family and the "A Disintegrin-like And Metalloproteinase with ThromboSpondin motifs" (ADAMTS) protein family are two related families of human proteins. The similarities and differences between these two families have been investigated using phylogenetic trees and homology modeling. The phylogenetic analysis indicates that the two families are well differentiated, even when only the common metalloprotease domain is taken into account. Within the ADAM family, several proteins are lacking the binding motif for the catalytic zinc in the active site and thus presumably lack any catalytic activity. These proteins tend to cluster within the ADAM phylogenetic tree and are expressed in specific tissues, suggesting a functional differentiation. The present analysis allows us to propose the following: (i) ADAMTS proteins have a conserved role in the human organism as proteases, with some differentiation in terms of substrate specificity; (ii) ADAM proteins can act as proteases and/or mediators of intermolecular interactions; (iii) proteolytically active ADAMs tend to be more ubiquitously expressed than the inactive ones.

Background: Colorectal cancer is a common malignancy of the gastrointestinal tract. It is the second cancer cause of death in females and third in males. Production of prolactin has been reported with several tumours. However, elevated prolactin plasma levels in colorectal cancer patients remained unclear., Methods: In this cross sectional study serum prolactin and carcinoembryonic antigen (CEA) concentrations were assayed using immunoradiometric assay kits, preoperatively in 47 patients, and the results were compared with 51 age and sex matched controls., Results: Prolactin and CEA concentration in patients were significantly more as compared with controls. Hyperprolactinemia was found in 36 (76.6%) patients, while 28 (59.6%) had high level of CEA., Conclusions: Prolactin may be a better tumour marker than CEA in patients with colorectal malignancy.

Objective: To examine the association between age on arrival in Britain and experiences and attitudes relating to female circumcision among young, single Somalis living in London., Design: The study population consisted of single male and female Somalis aged 16-22 years living in the Greater London area. Quantitative data were collected using a cross-sectional survey based on snowball sampling aiming to obtain data on 100 males and 100 females. Qualitative data were collected from 10 males and 10 infibulated females., Results: Quantitative data were obtained for 94 females and 80 males. Living in Britain from a younger age was associated with increased assimilation in terms of language, dress and socialising. Seventy per cent of the females reported being circumcised with two-thirds of operations being infibulation. Those who were living in Britain before the usual age range for circumcision (before age six) were less likely to be circumcised (42%) than those who arrived after the usual age range for circumcision (11 or older) (91%). During in-depth interviews, health and sexual problems due to female circumcision were described with great emotion and interviewees acknowledged the association between the importance of virginity for marriage and circumcision. Half of males who arrived aged 11 or older wanted a circumcised wife compared with less than a quarter of those who arrived at a younger age. Eighteen per cent of female respondents and 43% of males intended to circumcise any daughters. Females were less likely than males to agree with the assumptions about sexuality and religion that underpin the practice. Substantial proportions of respondents perceived that their parents' expectations in terms of marriage and circumcision were more traditional than their own., Conclusion: Living in Britain from a younger age appears to be associated with abandonment of female circumcision and with changes in the underlying beliefs on sexuality, marriage and religion that underpin it. Groups identified with more traditional views towards female circumcision include males, older generations, new arrivals and those who show few signs of social assimilation.

Steady-state plasma concentrations of clozapine and norclozapine, its major metabolite, as well as their sum and ratio (norclozapine/clozapine), were evaluated in 50 in- and outpatients taking clozapine and naturalistically recruited. Drug plasma concentrations were measured by means of a reversed-phase high-performance liquid chromatography (RPLC) method with an ultraviolet detection. Daily doses (milligrams per kilogram of body weight) of clozapine correlated positively with clozapine plasma parameters, except with the norclozapine/clozapine ratio, in all patients. When the patients were divided in subgroups with respect to gender, the corresponding plasma concentrations were no longer dose-related in men. A lack of significant correlation was observed also in patients (n=23) co-treated with typical neuroleptics. Conversely, dose-concentration correlations were significant in either smoker or nonsmoker patients. No significant relationship between body weight and clozapine plasma parameters was reported. Further, we observed (1) a trend towards higher medians of clozapine or total analytes in women than those reported in men (P=.09 and .07); (2) no significant difference in plasma levels obtained in subjects younger than 34 years and subjects 34 years old or older; (3) a trend towards higher norclozapine and clozapine plus norclozapine levels (P=.05 and .08) in nonsmoker than smoker patients; (4) no significant difference between clozapine plasma parameters measured in patients co-medicated with typical neuroleptics and in patients receiving clozapine alone.

The problem of the relationship between the surface B antigen and the parasitosis characterized by active penetration of the larvae through the skin has not yet been resolved. Conflicting results have been reported lately on this problem even though it is currently believed that HBsAg is found more often among patients infected by parasites than among healthy subjects. Serum samples from 67 Somalian patients infected by S. haematobium were tested for the presence of the surface B antigen by ELISA method. The HBsAg was found in 19.4 per cent of these patients, while among controls (90 cases) the frequency of HBsAg was of 10 per cent. A comparative analysis of the results obtained with various methods in Somalia shows that the frequency of HBsAg among subjects with urinary schistosomiasis is of 25.9 per cent with indirect haemoagglutination (IHA), of 19.4 per cent with ELISA method and of 14.8 per cent with radioimmunoassay (RIA). These observations seem to indicate that the problem of an increased frequency of HBsAg among patients with urinary schistosomiasis needs further investigation.

We have carried out an open clinical study in Somalia to evaluate the efficacy and safety of a simplified dosage schedule of metrifonate in the treatment of Schistosoma haematobium infection. The doses used were: I. 10 mg X kg-1 once daily for 3 days II. 5 mg X kg-1 thrice daily for one day III. 7.5 mg X kg-1 thrice daily for one day. We screened a total of 550 subjects in four villages for egg excretion in urine, and selected patients with more than 200 eggs per 10 ml of urine. In the initial phase of the study eight patients were assigned to each of the three dose schedules. In an extended study 38 additional patients were treated with regimen II which gave the best outcome in the initial study. Dosage Schedules I and III turned out to be toxic, and none of the patients was treated with all three doses. Adverse effects, such as abdominal colic, nausea, salivation, dizziness, and headache, were seen in almost all the patients in those two groups. Two patients from Group I reported that they fainted within 2 h after the second dose. None of the patients in Group II reported adverse effects. After 4-6 weeks follow-up, egg reduction was 96-100% for Groups I and II and the cure rate was around 60%. This study has shown that a shorter course of treatment with metrifonate might be equally effective and safer than the recommended dosage schedule with three doses of 7.5-10 mg X kg-1 fortnightly.