Perceptions of clinical clerks and interns of the University of the Philippines College of Medicine towards physical and rehabilitation medicine as a medical specialty

Objectives@#Perception about Physical and Rehabilitation Medicine provides information about awareness on identifying disabilities and managing their impact on activities of daily living; however, misconceptions about the field continue to exist among both students and physicians. This study aims to describe the perceptions of clinical clerks and interns towards the practice and role of Rehabilitation Medicine in management of patients. @*Methods@#This is a descriptive cross-sectional study. Students from the Learning Unit 6 and 7 of UP College of Medicine answered adapted online survey forms from a previous study and participated in online focus group discussions. Qualitative data were used to infer the perception of medical students towards the specialty. The effect of the respondent’s profile, background and affiliation on their knowledge, attitudes and perceptions were analyzed using One-Way ANOVA (α = 0.05). Qualitative data were analyzed using thematic analysis. @*Results@#Learning Unit 6 and 7 students were found to have a perceived broad level of knowledge with regards the specialty. The students associated the specialty with focus on holistic care, quality of life, interdisciplinary collaboration, and diversity of cases managed. No statistically significant differences were found between the perception among: 1) Learning Unit 6 and 7, 2) those with or without a previous encounter with the specialty, 3) allied medical and non-allied medical undergraduate courses in terms of: a) confidence in the knowledge (p = 0.489), b) familiarity with conditions managed (p = 0.93) and c) interest towards the specialty (p = 0.693). The Organ System Integrated (OSI) curriculum, which promotes horizontal and vertical integration of concepts, provided a wide understanding of the basic concepts related to physiatry. The students’ responses suggest a positive attitude towards Physical and Rehabilitation Medicine, as measured in their level of interest about knowing more regarding the specialty. Most common perceptions were that the specialty was multidisciplinary and holistic. However, the respondents’ perceptions regarding the roles of the Rehabilitation team were limited. @*Conclusion@#Learning unit level 6 and 7 students had a broad understanding of the practice and scope of the Physical and Rehabilitation Medicine specialty. Future researches can include other medical students in all year levels, including Learning Units 3, 4 and 5 of UPCM, to observe the development of their perceptions about the specialty throughout medical school.

Cannabis: a multifaceted plant with endless potentials.

Cannabis sativa, also known as "hemp" or "weed," is a versatile plant with various uses in medicine, agriculture, food, and cosmetics. This review attempts to evaluate the available literature on the ecology, chemical composition, phytochemistry, pharmacology, traditional uses, industrial uses, and toxicology of Cannabis sativa. So far, 566 chemical compounds have been isolated from Cannabis, including 125 cannabinoids and 198 non-cannabinoids. The psychoactive and physiologically active part of the plant is a cannabinoid, mostly found in the flowers, but also present in smaller amounts in the leaves, stems, and seeds. Of all phytochemicals, terpenes form the largest composition in the plant. Pharmacological evidence reveals that the plants contain cannabinoids which exhibit potential as antioxidants, antibacterial agents, anticancer agents, and anti-inflammatory agents. Furthermore, the compounds in the plants have reported applications in the food and cosmetic industries. Significantly, Cannabis cultivation has a minimal negative impact on the environment in terms of cultivation. Most of the studies focused on the chemical make-up, phytochemistry, and pharmacological effects, but not much is known about the toxic effects. Overall, the Cannabis plant has enormous potential for biological and industrial uses, as well as traditional and other medicinal uses. However, further research is necessary to fully understand and explore the uses and beneficial properties of Cannabis sativa.

Risk assessment of microplastics in freshwater sediments guided by strict quality criteria and data alignment methods.

Determining the risks of microplastics is difficult because data is of variable quality and cannot be compared. Although sediments are important sinks for microplastics, no holistic risk assessment framework is available for this compartment. Here we assess the risks of microplastics in freshwater sediments worldwide, using strict quality criteria and alignment methods. Published exposure data were screened for quality using new criteria for microplastics in sediment and were rescaled to the standard 1-5000 µm microplastic size range. Threshold effect data were also screened for quality and were aligned to account for the polydispersity of environmental microplastics and for their bioaccessible fraction. Risks were characterized for effects triggered by food dilution or translocation, using ingested particle volume and surface area as ecologically relevant metrics, respectively. Based on species sensitivity distributions, we determined Hazardous Concentrations for 5% of the species (HC5, with 95% CI) of 4.9 × 109 (6.6 × 107 - 1.9 × 1011) and 1.1 × 1010 (3.2 × 108 - 4.0 × 1011) particles / kg sediment dry weight, for food dilution and translocation, respectively. For all locations considered, exposure concentrations were either below or in the margin of uncertainty of the HC5 values. We conclude that risks from microplastics to benthic communities cannot be excluded at current concentrations in sediments worldwide.

Targeted Metabolomic Analysis in Alzheimer's Disease Plasma and Brain Tissue in Non-Hispanic Whites.

BACKGROUND: Metabolites are biological compounds reflecting the functional activity of organs and tissues. Understanding metabolic changes in Alzheimer's disease (AD) can provide insight into potential risk factors in this multifactorial disease and suggest new intervention strategies or improve non-invasive diagnosis. OBJECTIVE: In this study, we searched for changes in AD metabolism in plasma and frontal brain cortex tissue samples and evaluated the performance of plasma measurements as biomarkers. METHODS: This is a case-control study with two tissue cohorts: 158 plasma samples (94 AD, 64 controls; Texas Alzheimer's Research and Care Consortium - TARCC) and 71 postmortem cortex samples (35 AD, 36 controls; Banner Sun Health Research Institute brain bank). We performed targeted mass spectrometry analysis of 630 compounds (106 small molecules: UHPLC-MS/MS, 524 lipids: FIA-MS/MS) and 232 calculated metabolic indicators with a metabolomic kit (Biocrates MxP® Quant 500). RESULTS: We discovered disturbances (FDR≤0.05) in multiple metabolic pathways in AD in both cohorts including microbiome-related metabolites with pro-toxic changes, methylhistidine metabolism, polyamines, corticosteroids, omega-3 fatty acids, acylcarnitines, ceramides, and diglycerides. In AD, plasma reveals elevated triglycerides, and cortex shows altered amino acid metabolism. A cross-validated diagnostic prediction model from plasma achieves AUC = 82% (CI95 = 75-88%); for females specifically, AUC = 88% (CI95 = 80-95%). A reduced model using 20 features achieves AUC = 79% (CI95 = 71-85%); for females AUC = 84% (CI95 = 74-92%). CONCLUSION: Our findings support the involvement of gut environment in AD and encourage targeting multiple metabolic areas in the design of intervention strategies, including microbiome composition, hormonal balance, nutrients, and muscle homeostasis.

Extreme Lateral Supracerebellar Infratentorial Approach: Surgical Anatomy and Review of the Literature.

OBJECTIVE: The extreme lateral supracerebellar infratentorial (ELSI) approach has the potential to access several distinct anatomical regions that are otherwise difficult to reach. We have illustrated the surgical anatomy through cadaveric dissections and provided an extensive review of the literature to highlight the versatility of this approach, its limits, and comparisons with alternative approaches. METHODS: The surgical anatomy of the ELSI has been described using 1 adult-injected cadaveric head. Formalized noninjected brain specimens were also dissected to describe the brain parenchymal anatomy of the region. An extensive review of the literature was performed according to each targeted anatomical region. Illustrative cases are also presented. RESULTS: The ELSI approach allows for wide exposure of the middle and posterolateral incisural spaces with direct access to centrally located intra-axial structures such as the splenium, pulvinar, brainstem, and mesial temporal lobe. In addition, for skull base extra-axial tumors such as petroclival meningiomas, the ELSI approach represents a rapid and adequate method of access without the use of extensive skull base approaches. CONCLUSIONS: The ELSI approach represents one of the most versatile approaches with respect to its ability to address several anatomical regions centered at the posterior and middle incisural spaces. For intra-axial pathologies, the approach allows for access to the central core of the brain with several advantages compared with alternate approaches that frequently involve significant brain retraction and cortical incisions. In specific cases of skull base lesions, the ELSI approach is an elegant alternative to traditionally used skull base approaches, thereby avoiding approach-related morbidity.

A Controlled Trial of Rivaroxaban after Transcatheter Aortic-Valve Replacement.

BACKGROUND: Whether the direct factor Xa inhibitor rivaroxaban can prevent thromboembolic events after transcatheter aortic-valve replacement (TAVR) is unclear. METHODS: We randomly assigned 1644 patients without an established indication for oral anticoagulation after successful TAVR to receive rivaroxaban at a dose of 10 mg daily (with aspirin at a dose of 75 to 100 mg daily for the first 3 months) (rivaroxaban group) or aspirin at a dose of 75 to 100 mg daily (with clopidogrel at a dose of 75 mg daily for the first 3 months) (antiplatelet group). The primary efficacy outcome was the composite of death or thromboembolic events. The primary safety outcome was major, disabling, or life-threatening bleeding. The trial was terminated prematurely by the data and safety monitoring board because of safety concerns. RESULTS: After a median of 17 months, death or a first thromboembolic event (intention-to-treat analysis) had occurred in 105 patients in the rivaroxaban group and in 78 patients in the antiplatelet group (incidence rates, 9.8 and 7.2 per 100 person-years, respectively; hazard ratio with rivaroxaban, 1.35; 95% confidence interval [CI], 1.01 to 1.81; P = 0.04). Major, disabling, or life-threatening bleeding (intention-to-treat analysis) had occurred in 46 and 31 patients, respectively (4.3 and 2.8 per 100 person-years; hazard ratio, 1.50; 95% CI, 0.95 to 2.37; P = 0.08). A total of 64 deaths occurred in the rivaroxaban group and 38 in the antiplatelet group (5.8 and 3.4 per 100 person-years, respectively; hazard ratio, 1.69; 95% CI, 1.13 to 2.53). CONCLUSIONS: In patients without an established indication for oral anticoagulation after successful TAVR, a treatment strategy including rivaroxaban at a dose of 10 mg daily was associated with a higher risk of death or thromboembolic complications and a higher risk of bleeding than an antiplatelet-based strategy. (Funded by Bayer and Janssen Pharmaceuticals; GALILEO ClinicalTrials.gov number, NCT02556203.).

Perceptions of clinical clerks and interns of the University of the Philippines College of Medicine towards physical and rehabilitation medicine as a medical specialty

Objectives@# Perception about Physical and Rehabilitation Medicine provides information about awareness on identifying disabilities and managing their impact on activities of daily living; however, misconceptions about the field continue to exist among both students and physicians. This study aims to describe the perceptions of clinical clerks and interns towards the practice and role of Rehabilitation Medicine in management of patients. @*Methods@#This is a descriptive cross-sectional study. Students from the Learning Unit 6 and 7 of UP College of Medicine answered adapted online survey forms from a previous study and participated in online focus group discussions. Qualitative data were used to infer the perception of medical students towards the specialty. The effect of the respondent’s profile, background and affiliation on their knowledge, attitudes and perceptions were analyzed using One-Way ANOVA (α = 0.05). Qualitative data were analyzed using thematic analysis. @*Results@#Learning Unit 6 and 7 students were found to have a perceived broad level of knowledge with regards the specialty. The students associated the specialty with focus on holistic care, quality of life, interdisciplinary collaboration, and diversity of cases managed. No statistically significant differences were found between the perception among: 1) Learning Unit 6 and 7, 2) those with or without a previous encounter with the specialty, 3) allied medical and non-allied medical undergraduate courses in terms of: a) confidence in the knowledge (p = 0.489), b) familiarity with conditions managed (p = 0.93) and c) interest towards the specialty (p = 0.693). The Organ System Integrated (OSI) curriculum, which promotes horizontal and vertical integration of concepts, provided a wide understanding of the basic concepts related to physiatry. The students’ responses suggest a positive attitude towards Physical and Rehabilitation Medicine, as measured in their level of interest about knowing more regarding the specialty. Most common perceptions were that the specialty was multidisciplinary and holistic. However, the respondents’ perceptions regarding the roles of the Rehabilitation team were limited. @*Conclusion@#Learning unit level 6 and 7 students had a broad understanding of the practice and scope of the Physical and Rehabilitation Medicine specialty. Future researches can include other medical students in all year levels, including Learning Units 3, 4 and 5 of UPCM, to observe the development of their perceptions about the specialty throughout medical school.

Glycemic and Insulinemic Responses of Vegetables and Beans Powders Supplemented Chapattis in Healthy Humans: A Randomized, Crossover Trial.

Vegetables and beans are nutrient-dense foods with innate potential to mediate diabetes in a variety of cultures. The present study aims at evaluating vegetables and beans for assessing their glycemic index and response in raising glucose levels in human model. Powdered formulations of vegetables and beans were designed to modulate glycemic response of carbohydrate-rich staples. A randomized, crossover trial was conducted in healthy young adults (n = 24) who were challenged with vegetable powder-supplemented chapatti (VPSC), bean powder-supplemented chapatti (BPSC) and all-purpose wheat flour chapatti (APFC) to evaluate their postprandial glucose (PPG) and postprandial insulin (PPI) responses. In comparison with APFC, feeding VPSC and BPSC to healthy volunteers anticipated significant reduction in PPG (44% reduction in incremental area under the curve (AUC) for VPSC and 46% reduction in incremental AUC for BPSC, p = 0.005). Likewise, significant reduction in PPI levels was observed for VPSC (59%, p = 0.012) and BPSC (47%, p = 0.002) compared to APFC-treated group. The study concludes wheat flour enrichment with vegetables and beans powder as a viable approach to develop cost effective and culturally acceptable low glycemic foods bearing acceptable sensory attributes.

The Microbiome and Atopic Dermatitis: A Review.

The microbiome is defined as the sum of microbes, their genomes, and interactions in a given ecological niche. Atopic dermatitis is a multifactorial chronic inflammatory skin disease leading to dryness and itchiness of the skin. It is often associated with comorbidities such as allergic rhinoconjunctivitis and asthma. Today, culture-free techniques have been established to define microbes and their genomes that may be both detrimental and beneficial for their host. There are signs that microbes, both on skin and in the gut, may influence the course of atopic dermatitis. Antiseptic treatment has been used for decades, however now, with the help of traditional culture-based methods and modern metagenomics, we are beginning to understand that targeted treatment of dysbiosis may possibly become part of an integrated therapy plan in the future.

Easing anxiety in preparation for pediatric magnetic resonance imaging: a pilot study using animal-assisted therapy.

BACKGROUND: Children undergoing magnetic resonance imaging (MRI) can experience negative emotions both before and during their scan, causing them to move and often necessitating the use of procedural sedation. Several strategies to improve patient compliance have been attempted. OBJECTIVE: This study was designed to evaluate the effectiveness of a non-pharmacological intervention to reduce anxiety in pediatric patients preparing for MRI using animal-assisted therapy. MATERIALS AND METHODS: An animal intervention pilot study was performed in patients who agreed in advance to interact with a dog. Patients and caregivers filled out questionnaires, including questions designed to capture changes in patient emotion before and after the intervention. MRI diagnostic quality was compared to age- and gender-matched control groups with and without general anesthesia. RESULTS: The intervention in 21 patients comparing pre- and post-scan surveys demonstrated a statistically significant improvement in patient anxiety levels (P<0.01). Diagnostic MRI scans were achieved in 19/21 (90%), with no significant difference in exam quality or times compared against control groups. The majority of caregivers and staff members agreed strongly that patients benefited from the therapy dog's presence. CONCLUSION: The use of animal-assisted therapy in a pilot group in our MRI division resulted in a beneficial effect on patients' emotional status, easing anxiety in preparation for scheduled scans, without impacting MRI quality or duration. Further randomized studies will be needed to demonstrate its significance in reducing sedation rates in children undergoing MRI.

Cytokine Profile of Patients with Allergic Rhinitis Caused by Pollen, Mite, and Microbial Allergen Sensitization.

Allergic rhinitis (AR) is especially prevalent among the population of large cities. Immunologically, the airway epithelium is a region where the population of allergen-presenting cells concentrates. These cells actively express a group of receptors of the innate immune system. A specific cytokine profile is its representation. The study was aimed at evaluating the cytokine profile in patients with seasonal and perennial allergic rhinitis. The cytokine profile of nasal secretion and blood serum of 44 patients with AR was studied. 24 of them had seasonal allergic rhinitis (SAR), and 20 patients suffered from perennial allergic rhinitis (PAR). The patients' age ranged from 4 to 60 years. It was determined in our study that the activation of the GM-CSF production retained in patients with PAR sensitized to mite allergen components (Dermatophagoides pteronyssinus). There was a higher production profile of TNF-α and TSLP in nasal secretion in the patients with perennial allergic rhinitis and additional high sensitization to SEs. Sensitization to mold fungal allergen components significantly increases in patients with seasonal allergic rhinitis. They demonstrated high level of sensitization to the Aspergillus fumigatus component m3. Thus, along with other clinical trials, the study performed would clarify some aspects of molecular pathogenesis of human allergic rhinitis.

Selaginella bryopteris Aqueous Extract Improves Stability and Function of Cryopreserved Human Mesenchymal Stem Cells.

The effective long-term cryopreservation of human mesenchymal stem cells (MSCs) is an essential prerequisite step and represents a critical approach for their sustained supply in basic research, regenerative medicine, and tissue engineering applications. Therefore, attempts have been made in the present investigation to formulate a freezing solution consisting of a combination of Selaginella bryopteris water-soluble extract with and without dimethyl sulfoxide (Me2SO) for the efficient long-term storage of human umbilical cord blood- (hUCB-) derived MSCs. The cryopreservation experiment using the formulated freezing solution was further performed with hUCB MSCs in a controlled rate freezer. A significant increase in postthaw cell viability and cell attachment of MSCs was achieved with freezing medium containing Selaginella bryopteris water extract along with 10% Me2SO as compared to the freezing medium containing Me2SO (10% v/v) alone. Furthermore, the decreasing apoptotic events and reactive oxygen species production along with increasing expression of heat shock proteins also confirmed the beneficial effect of Selaginella bryopteris water extract. The beneficial effect of Selaginella bryopteris water extract was validated by its ability to render postpreservation high cell viability. In conclusion, the formulated freezing solution has been demonstrated to be effective for the standardization of cryopreservation protocol for hMSCs.

Protective Effect of Green Tea (Camellia sinensis (L.) Kuntze) against Prostate Cancer: From In Vitro Data to Algerian Patients.

Green tea (GT) has been studied for its effects as antioxidant and cancer-preventive agent. Epidemiological studies showed that GT consumption decreases the risk for prostate cancer (PC). To investigate whether erythrocyte oxidative stress (OS) is associated with PC and whether daily consumption of GT improves the oxidative phenotype, we performed a study in a group of Algerian PC patients, preceded by an in vitro study to characterize composition and antioxidant/antiproliferative activities of the GT used. This contained a high content of phenolic and flavonoid compounds, demonstrating in vitro antioxidant activity and significant antiproliferative effect on human prostate cancer PC-3 cell line. Seventy PC patients and 120 age-matched healthy subjects participated in the study, with glutathione (GSH), malondialdehyde (MDA), and catalase activity evaluated before and after GT consumption. The results showed a reduced GSH and catalase activity and a high level of MDA in erythrocytes from PC patients. The consumption of 2-3 cups per day of GT during 6 months significantly increased GSH concentration and catalase activity and decreased MDA concentration. In conclusion, GT significantly decreased OS in Algerian PC patients. Regular consumption of GT for a long period may prevent men from developing PC or at least delay its progression.

Trial design: Rivaroxaban for the prevention of major cardiovascular events after transcatheter aortic valve replacement: Rationale and design of the GALILEO study.

BACKGROUND: Optimal antithrombotic treatment after transcatheter aortic valve replacement (TAVR) is unknown and determined empirically. The direct factor Xa inhibitor rivaroxaban may potentially reduce TAVR-related thrombotic complications and premature valve failure. DESIGN: GALILEO is an international, randomized, open-label, event-driven, phase III trial in more than 1,520 patients without an indication for oral anticoagulation who underwent a successful TAVR (ClinicalTrials.govNCT02556203). Patients are randomized (1:1 ratio), 1 to 7days after a successful TAVR, to either a rivaroxaban-based strategy or an antiplatelet-based strategy. In the experimental arm, subjects receive rivaroxaban (10mg once daily [OD]) plus acetylsalicylic acid (ASA, 75-100mg OD) for 90days followed by rivaroxaban alone. In the control arm, subjects receive clopidogrel (75mg OD) plus ASA (as above) for 90days followed by ASA alone. In case new-onset atrial fibrillation occurs after randomization, full oral anticoagulation will be implemented with maintenance of the original treatment assignment. The primary efficacy end point is the composite of all-cause death, stroke, myocardial infarction, symptomatic valve thrombosis, pulmonary embolism, deep venous thrombosis, and systemic embolism. The primary safety end point is the composite of life-threatening, disabling, and major bleeding, according to the Valve Academic Research Consortium definitions. CONCLUSIONS: GALILEO will test the hypothesis that a rivaroxaban-based antithrombotic strategy reduces the risk of thromboembolic complications post-TAVR with an acceptable risk of bleeding compared with the currently recommended antiplatelet therapy-based strategy in subjects without need of chronic oral anticoagulation.

Randomized controlled trial of prolonged exposure using imaginal exposure vs. virtual reality exposure in active duty soldiers with deployment-related posttraumatic stress disorder (PTSD).

OBJECTIVE: Prolonged exposure (PE) is an evidence-based psychotherapy for posttraumatic stress disorder (PTSD) but there is limited research with active-duty military populations. Virtual reality exposure (VRE) has shown promise but randomized trials are needed to evaluate efficacy relative to existing standards of care. This study evaluated the efficacy of VRE and PE for active duty soldiers with PTSD from deployments to Iraq and Afghanistan. METHOD: Active-duty soldiers (N = 162) were randomized to 10-sessions of PE, VRE, or a minimal attention waitlist (WL). Blinded assessors evaluated symptoms at baseline, halfway through treatment, at posttreatment, and at 3- and 6-month follow-ups using the Clinician Administered PTSD Scale (CAPS). RESULTS: Intent-to-treat analyses found that both PE and VRE resulted in significant reductions in PTSD symptoms relative to those in the WL. The majority of patients demonstrated reliable change in PTSD symptoms. There was no difference between PE and VRE regarding treatment drop out before completing 10 sessions (44 and 41% for VRE and PE, respectively). Contrary to hypotheses, analyses at posttreatment did not show that VRE was superior to PE. Post hoc analyses found that PE resulted in significantly greater symptom reductions than VRE at 3- and 6-month follow-up. Both treatments significantly reduced self-reported stigma. CONCLUSIONS: PE is an efficacious treatment for active-duty Army soldiers with PTSD from deployments to Iraq or Afghanistan. Results extend previous evidence supporting the efficacy of PE to active-duty military personnel and raise important questions for future research on VRE. (PsycINFO Database Record

Knowledge, attitudes and clinical practice of blood products prescribers in Niamey.

AIM OF THE STUDY: The lack of traceability and monitoring of blood donors and transfused patients constitute a barrier to the most basic rules of haemovigilance and overall good transfusion practices. This study draws up an inventory of knowledge, attitudes and clinical practice of blood prescribers in Niamey. MATERIALS AND METHODS: A questionnaire was administered to 180 prescribers of blood products in Niamey in 2011. Questions were related to basic informations on blood transfusion and clinical use of blood. Analyses were performed using SAS 9.3 version. RESULTS: The sample consisted of 180 respondents from several professional categories: 51 physicians (28.33%), 10 medical students (5.56%), 84 nurses (46.67%), 15 anaesthesiologist assistant (8.33%) and 20 midwives (11.11%). Among these, 22.2% received training in blood transfusion safety. Half of the respondents (50.8%) got between 50 and 75% of correct answers, 45.8% got less than 50% correct while 3.35% scored more than 75% correct answers. The overall quality of responses was higher among physicians compared to other prescribers (P<0.0001); among respondents who received training in transfusion safety (P<0.0001); and among males (P=0.0306). For some items, subjects with more experience scored the best. CONCLUSION: The level of knowledge is still inadequate. More training in transfusion practices is necessary for prescribers of blood products. Accompanying measures to improve transfusion practice must be considered or strengthened through assessments, knowledge update/upgrade (regular, ongoing training) and establishment of active and motivated hospital transfusion committees.

Cutaneous Collagenous Vasculopathy: A Rare Form of Microangiopathy Successfully Treated with a Combination of Multiplex Laser and Optimized Pulsed Light with a Review of the Literature.

Cutaneous collagenous vasculopathy (CCV) is a rare idiopathic microangiopathy of the cutaneous vasculature characterized histologically by the presence of dilated small blood vessels with flat endothelial cells and thickened walls containing hyaline material in the upper dermis. We report an elderly patient presenting with an extensive form of CCV involving the trunk, upper and lower limbs. She was treated with Multiplex PDL 595-nm/Nd:YAG 1,064-nm laser and optimized pulsed light. This approach, which has never been reported for CCV so far, resulted in a striking and almost complete clearance of the widespread lesions. We here review our knowledge about CCV and therapeutic options available with a survey of the literature.

The effect of plant sterols and different low doses of omega-3 fatty acids from fish oil on lipoprotein subclasses.

SCOPE: Consumption of a low-fat spread enriched with plant sterols (PS) and different low doses (<2 g/day) of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) from fish oil reduces serum triglycerides (TGs) and low-density lipoprotein-cholesterol (LDL-Chol) and thus beneficially affects two blood lipid risk factors. Yet, their combined effects on TG and Chol in various lipoprotein subclasses have been investigated to a limited extent. METHODS AND RESULTS: In a randomized, double-blind, placebo-controlled, parallel study, we determined TG and Chol in 13 LP subclasses in fasting serum of 282 hypercholesterolemic subjects, who consumed either a placebo spread or one of the four spreads containing PS (2.5 g/day) and EPA+DHA (0.0, 0.9, 1.3, and 1.8 g/day) for 4 weeks. After PS treatment, total LDL-Chol was reduced, which was not further changed by EPA+DHA. No shift in the LDL-Chol particle distribution was observed. The addition of EPA+DHA to PS dose-dependently reduced VLDL-Chol and VLDL-TG mainly in larger particles. Furthermore, the two highest doses of EPA+DHA increased Chol and TG in the larger HDL particles, while these concentrations were decreased in the smallest HDL particles. CONCLUSION: The consumption of a low-fat spread enriched with both PS and EPA+DHA induced shifts in the lipoprotein distribution that may provide additional cardiovascular benefits over PS consumption alone.

The ultimate radiochemical nightmare: upon radio-iodination of Botulinum neurotoxin A, the introduced iodine atom itself seems to be fatal for the bioactivity of this macromolecule.

BACKGROUND: Botulinum neurotoxin A (BoNT-A) is a highly neurotoxic drug and frequently used in patients. Knowledge on the optimal way of administration of BoNT-A and its subsequent distribution is still rather limited. An accurate method for monitoring these processes might be the use of radiolabelled BoNT-A. In this paper, we report our feasibility study on labelling BoNT-A with high-dose iodine-125 ((125)I) via IODOGEN-coated BoNT-A method. METHODS: Using cetuximab as model substrate for BoNT-A, a miniaturization of the IODOGEN-coated mAb method was developed with special attention to the minimum required amount of the oxidant IODOGEN, while the amount of substrate, reaction volume and reaction time were downsized. Labelling efficiency and radiochemical purity were determined by TLC, integrity by SDS-PAGE and HPLC and immunoreactivity by cell-binding assay. BoNT-A (50 µg) was labelled with (125)I by coating with 2.5 µg IODOGEN, in a total reaction volume of 250 µL and a reaction time of 90 s. (125)I-BoNT-A was purified by size exclusion chromatography (PD10 column) using ascorbic acid solution (5 mg/ml, pH = 5) as eluent. Quality analysis of (125)I-BoNT-A was performed by an in vitro bladder strip model, an electrochemiluminescence assay and an Endopep assay. RESULTS: Cetuximab (50 µg) labelling with (125)I (15 to 150 MBq) resulted in a labelling efficiency of 70% to 80%, a radiochemical purity of >99%, an immunoreactivity of >95% and a retained integrity on SDS; HPLC analysis revealed partly affected integrity when 110 to 150 MBq (125)I was used, i.e. when the averaged I/mAb molar ratio exceeded 3. Addition of HEPES (20 mM) and lactose (1.25%) (lyophilized BoNT-A contains HEPES and lactose) decreased the labelling efficiency to 44% to 54%. BoNT-A (50 µg) labelling with (125)I (97.2 to 98.3 MBq) resulted in labelling efficiency of 51% to 52% with a radiochemical purity >98.5%, a specific activity of 150.5 to 152.9 MBq/nmol and an I/BoNT-A molar ratio of 1.86 to 1.90. The in vitro bladder strip model showed no bioactivity of (125)I-BoNT-A when compared to unlabelled BoNT-A. The electrochemiluminescence and Endopep assay demonstrated around 10% and 15% bioactivity of (125)I-BoNT-A compared to unlabelled BoNT-A, respectively. The remaining bioactivity correlates within the Poisson distribution with the amount of BoNT-A molecules that does not bear an iodine atom. CONCLUSIONS: BoNT-A was successfully radio-iodinated with an activity high enough to enable in vivo measurement of nanograms of BoNT-A, which could be used in studying optimization of administration techniques of BoNT-A. The bioactivity of a BoNT-A molecule is, however, lost upon the introduction of an iodine atom into the tyrosine moiety of this sensitive molecule.

Dietary medium chain fatty acid supplementation leads to reduced VLDL lipolysis and uptake rates in comparison to linoleic acid supplementation.

Dietary medium chain fatty acids (MCFA) and linoleic acid follow different metabolic routes, and linoleic acid activates PPAR receptors. Both these mechanisms may modify lipoprotein and fatty acid metabolism after dietary intervention. Our objective was to investigate how dietary MCFA and linoleic acid supplementation and body fat distribution affect the fasting lipoprotein subclass profile, lipoprotein kinetics, and postprandial fatty acid kinetics. In a randomized double blind cross-over trial, 12 male subjects (age 51±7 years; BMI 28.5±0.8 kg/m2), were divided into 2 groups according to waist-hip ratio. They were supplemented with 60 grams/day MCFA (mainly C8:0, C10:0) or linoleic acid for three weeks, with a wash-out period of six weeks in between. Lipoprotein subclasses were measured using HPLC. Lipoprotein and fatty acid metabolism were studied using a combination of several stable isotope tracers. Lipoprotein and tracer data were analyzed using computational modeling. Lipoprotein subclass concentrations in the VLDL and LDL range were significantly higher after MCFA than after linoleic acid intervention. In addition, LDL subclass concentrations were higher in lower body obese individuals. Differences in VLDL metabolism were found to occur in lipoprotein lipolysis and uptake, not production; MCFAs were elongated intensively, in contrast to linoleic acid. Dietary MCFA supplementation led to a less favorable lipoprotein profile than linoleic acid supplementation. These differences were not due to elevated VLDL production, but rather to lower lipolysis and uptake rates.