The effect of abo and rh blood group antigens on admission to intensive care unit and mortality in patients with COVID-19 infection.
The aim of this study is to analyze the prognostic significance of ABO and Rh blood group antigens along with various parameters in patients followed-up with the diagnosis of COVID-19. We evaluated 397 patients who were follow-up and treated due to COVID-19 infections. The ages, genders, chronic diseases, ABO and Rh blood group antigens, admission rates to Intensive Care Units (ICU), and mortality rates of the patients were analyzed. The mean age of the 397 patients with COVID-19 was 47±17 years. In the blood group analysis of the patients, A Rh-positive (A +) was the most frequently seen blood type (176 patients, 44.3%) followed by O Rh-positive (0 +) (109 patients, 27,5%); 38 patients were Rh negative (Rh -) (9,6%). 53 of the patients (13,4%) were followed in ICU and 29 patients died (7,3%). Neither mortality nor admission to ICU was seen for Rh - group. The comparison of Rh groups concerning the need for ICU admission revealed a significantly high rate of ICU admission in the Rh + group (p=0,011), while no significant relationship was found between mortality and Rh antigen (p=0,069). The most frequently seen blood type among COVID-19 patients was A +. The Rh + blood group was found in all cases who were admitted to ICU and had a death outcome. The Rh + blood group was found in a significantly high number of patients who were admitted to ICU, while no significant relationship was found between mortality and Rh blood group.


The Sensorimotor System, Part II: The Role of Proprioception in Motor Control and Functional Joint Stability.
To discuss the role of proprioception in motor control and in activation of the dynamic restraints for functional joint stability. Information was drawn from an extensive MEDLINE search of the scientific literature conducted in the areas of proprioception, motor control, neuromuscular control, and mechanisms of functional joint stability for the years 1970-1999. Proprioception is conveyed to all levels of the central nervous system. It serves fundamental roles for optimal motor control and sensorimotor control over the dynamic restraints. Although controversy remains over the precise contributions of specific mechanoreceptors, proprioception as a whole is an essential component to controlling activation of the dynamic restraints and motor control. Enhanced muscle stiffness, of which muscle spindles are a crucial element, is argued to be an important characteristic for dynamic joint stability. Articular mechanoreceptors are attributed instrumental influence over gamma motor neuron activation, and therefore, serve to indirectly influence muscle stiffness. In addition, articular mechanoreceptors appear to influence higher motor center control over the dynamic restraints. Further research conducted in these areas will continue to assist in providing a scientific basis to the selection and development of clinical procedures.


Expression of c-Fos in response to stressogenic stimuli in the amygdala of old vs. young rats--a preliminary study.
During aging many of the brain functions became deteriorated or altered. One of the most important age related changes is an increase of anxiety level, reported both in humans and in animals. Our study was intended to compare c-fos gene expression in amygdala, the key structure in anxiety/fear regulation, in old (24 months) and young (4 months) rats exposed to various behavioral stimulations. There were no differences between age groups in basal c-Fos expression. After social encounter c-Fos expression level in amygdala increased significantly, but still remained independent on age. Significant differences between both groups appeared after open field test and immobilization test. Contrary to the findings on young adults indicating the correlation between increased anxiety level and higher c-Fos expression, old rats showed increased anxiety together with significantly lower c-Fos expression.


Individual fracture risk and the cost-effectiveness of bisphosphonates in patients using oral glucocorticoids.
There are few data on the cost-effectiveness of bisphosphonates with oral glucocorticoids (GCs). An individual patient-based pharmaco-economic model was developed. Data were obtained from a cohort of oral GC users aged 40+ (n = 190 000) in the UK General Practice Research Database. Individualized fracture and mortality risks were calculated specific for age, sex, daily and cumulative GC dose, indication and other clinical risk factors. UK costs of medication and direct costs of fracture were obtained from National Institute for Clinical Excellence and used to estimate costs per quality-adjusted life-year (QALY) gained and fracture prevented for bisphosphonates in patients treated for 5 yrs with GCs. With the use of 5 mg GCs daily, the cost per one QALY gained with bisphosphonates was 41k UK pounds (95% confidence intervals 22-72k) in women aged <60 [men 40k pounds (29-54k)], 17k pounds (13-24k) in women aged 60-79 [men 43k pounds (31-60k)], 5k pounds(3-6k) in women aged 80+ [men 35k pounds (25-46k)]. With 15 mg GC, these figures were 17k pounds (14-21k), 13k pounds (10-16k) and 15k pounds (9-26k) in women and 22k pounds (17-26k), 34 pounds (23-53k) and 33k pounds (27-42k) in men, respectively. When stratifying by overall fracture risk and life expectancy at the start of GC therapy, cost per QALY increased with decreasing life expectancy. Patients with rheumatoid arthritis had comparatively better cost-effectiveness, given higher fracture risk and better life expectancy. The cost-effectiveness of bisphosphonates varied substantially. Bisphosphonates can be considered cost-effective in patients with higher fracture risks, such as elderly patients (with a life expectancy over 5 yrs), and younger patients with a fracture history, low body mass index, rheumatoid arthritis or using high GC doses.


Evolution of complexity in motor patterns and jaw musculature of tetraodontiform fishes
The prey-processing behavior and jaw-adducting musculature of tetraodontiform fishes provide a novel system for studying the evolution of muscles and their function. The history of this clade has involved a pattern of repeated 'duplications' of jaw muscles by physical subdivision of pre-existing muscles. As a result, the number of adductor mandibulae muscles in different taxa varies from as few as two to as many as eight. We used electromyography (EMG) to quantify motor-pattern variation of adductor mandibulae muscles in four tetraodontiform species during feeding events on prey items that varied in durability and elusiveness. Statistical analyses of variation in EMG variables revealed significant differences in motor patterns between duplicated muscles derived from a common ancestral muscle in seven of nine cases examined. Overall individual EMG timing variables (e.g. relative onset or duration of bursts) were slightly less likely to diverge functionally than amplitude variables (e.g. relative intensity of bursts). Functional divergence was found in significant overall differences between muscles and twice as frequently in significant muscle-by-prey interaction terms. Such interactions represent an underappreciated way in which motor patterns can evolve and diversify. Regional variation was documented in undivided muscles in two species, indicating that it is possible for functional subdivision to precede anatomical subdivision. This study shows that phylogenetic increases in the number of tetraodontiform jaw adductor muscles have been associated with increases in the functional complexity of the jaws at the level of muscle activation patterns.


Variable torque prescription: state of art.
The variable prescription is widely described under the clinical aspect: the clinics is the result of the evolution of the state-of-the-art, aspect that is less considered in the daily literature. The state-of-the-art is the key to understand not only how we reach where we are but also to learn how to manage propely the torque, focusing on the technical and biomechanical purpos-es that led to the change of the torque values over time. The aim of this study is to update the clinicians on the aspects that affect the torque under the biomechanical sight, helping them to understand how to managing it, following the "timeline changes" in the different techniques so that the Variable Prescription Orthodontic (VPO) would be a suitable tool in every clinical case.


Maintaining high moisture content of macadamia nuts-in-shell during storage induces brown centres in raw kernels.
Kernel brown centres in macadamia are a defect causing internal discolouration of kernels. This study investigates the effect on the incidence of brown centres in raw kernel after maintaining high moisture content in macadamia nuts-in-shell stored at temperatures of 30°C, 35°C, 40°C and 45°C. Brown centres of raw kernel increased with nuts-in-shell storage time and temperature when high moisture content was maintained by sealing in polyethylene bags. Almost all kernels developed the defect when kept at high moisture content for 5 days at 45°C, and 44% developed brown centres after only 2 days of storage at high moisture content at 45°C. This contrasted with only 0.76% when stored for 2 days at 45°C but allowed to dry in open-mesh bags. At storage temperatures below 45°C, there were fewer brown centres, but there were still significant differences between those stored at high moisture content and those allowed to dry (P < 0.05). Maintenance of high moisture content during macadamia nuts-in-shell storage increases the incidence of brown centres in raw kernels and the defect increases with time and temperature. On-farm nuts-in-shell drying and storage practices should rapidly remove moisture to reduce losses. Ideally, nuts-in-shell should not be stored at high moisture content on-farm at temperatures over 30°C.


[Tyndallometry for follow-up of iodine-125 brachytherapy of uveal malignant melanomas. Report of 2 patients].
Previous studies that used the noninvasive laser flare-cell meter (LFCM) have demonstrated impairment of the blood-aqueous barriers in eyes with uveal melanoma. Herein we report the use of the LFCM in the follow-up of brachytherapy in 2 patients after radiation therapy with iodine 125 for choroidal melanoma. Two women (59-and 57-years-old) with choroidal melanoma who were treated with iodine 125-plaque, were followed-up for 24 and 36 months, respectively. Complete ophthalmological examination including tyndallometry and echography were performed regularly. Following radiation, patient 1 showed decreasing flare values, that returned to normal level one year after radiation (5.9 photon counts/ms). The decrease in flare values correlated with fundoscopic and ultrasonographic signs of tumor regression. After 14 months, flare values suddenly increased up to 15 photon counts/ms, and fluorescein angiography revealed signs of radiation retinopathy. In patient 2, flare values (18.0 photon counts/ms) did not decrease after radiation but showed further increase one year after radiation (39.0 photon counts/ms). Slitlamp biomicroscopy revealed segmental iris neovascularization from 6 to 9 hours, corresponding to the site of the previous plaque application. Measurement of aqueous flare with the LFCM appears to be a useful ancillary diagnostic method in following patients after radiation therapy for uveal melanoma. In eyes that show an increase of aqueous flare months or years after radiation therapy, recurrence of the tumor, radiation retinopathy and iris neovascularization should be excluded.


The pregnancy and oncology outcome of fertility-sparing management for synchronous primary neoplasm of endometrium and ovary.
To investigate the efficacy of fertility-preserving treatment for young women with synchronous primary neoplasm of endometrium and ovary. We retrospectively reviewed eight patients with concurrent primary grade 1 presumed stage IA endometrioid endometrial adenocarcinoma (EEA) or endometrial atypical hyperplasia (EAH) and primary stage I ovarian tumors who underwent fertility-sparing treatment in the Obstetrics and Gynecology Hospital of Fudan University between April 2016 and December 2022. Synchronous endometrial and ovarian cancers (SEOC) accounted for 50% of these eight patients. The median age of patients was 30.5 years (range, 28-34 years). None of them received chemotherapy. The median treatment time was 4 months (range, 3-8 months). 87.5% (7/8) cases achieved complete response (CR), and the median time to CR was 3.8 months (range, 1.5-7.7 months). Among patients who got CR, none of them showed any signs of recurrence. Pregnancies and successful deliveries were achieved in 4 of 5 patients. Till September 2023, the median follow-up period was 50.5 months (range:15.2-85.2 months). Fertility-sparing treatment is feasible for highly selected patients with synchronous neoplasm of the endometrium and ovary, but strict screening and monitoring are mandatory. Though the results of our limited cases are encouraging, long follow-up and more clinical data are required. Enrolled patients must be fully informed of the risks during conservative treatment.


Comparative cholesterol lowering properties of vegetable oils: beyond fatty acids.
Our laboratory has previously reported that the hypolipidemic effect of rice bran oil (RBO) is not entirely explained by its fatty acid composition. Although RBO has up to three times more serum cholesterol-raising saturated fatty acids (SATS) than some unsaturated vegetable oils, we hypothesized that its greater content of the unsaponifiables would compensate for its high SATS and yield comparable cholesterol-lowering properties to other vegetable oils with less SATS. To study the comparative effects of different unsaturated vegetable oils on serum lipoprotein levels, nine cynomologus monkeys (Macaca fascicularis) were fed diets, for four weeks, in a Latin square design, containing rice bran, canola or corn oils (as 20% of energy) in a basal mixture of other fats to yield a final dietary fat concentration of 30% of energy. All animals were fed a baseline diet containing 36% of energy as fat with 15% SATS, 15% monounsaturated fatty acids (MONOS) and 6% polyunsaturated fatty acids (POLYS). Despite the lower SATS and higher MONOS content of canola oil and the higher POLYS content of corn oil, RBO produced similar reductions in serum total cholesterol (TC) (-25%) and low density lipoprotein cholesterol (LDL-C) (-30%). In addition, as compared to the baseline diet, the reduction in serum TC and LDL-C cholesterol with RBO was not accompanied by reductions in high density lipoprotein cholesterol (HDL-C) which occurred with the other two dietary oils. Using predictive equations developed from data gathered from several studies with non-human primates, we noted that the observed serum TC and LDL-C lowering capabilities of the RBO diet were in excess of those predicted based on the fatty acid composition of RBO. These studies suggest that non-fatty acid components (unsaponifiables) of RBO can contribute significantly to its cholesterol-lowering capability.


Fungal diversity and mycotoxins detected in maize stored in silo-bags: a review.
Silo-bags are hermetic storage systems that inhibit fungal growth because of their atmosphere with low humidity, as well as low pH and O2 concentrations, and a high CO2 concentration. If a silo-bag with stored maize loses its hermetic nature, it favors the development of fungi and the production of mycotoxins. To the best of our knowledge, this is the first review on the diversity of fungal species and mycotoxins that were reported in maize stored under the environmental conditions provided by silo-bags. The genera Penicillium, Aspergillus and Fusarium were found more frequently, whereas Acremonium spp., Alternaria sp., Candida sp., Cladosporium sp., Debaryomyces spp., Epiconum sp., Eupenicillium spp., Eurotium sp., Eurotium amstelodami, Hyphopichia spp., Hyphopichia burtonii, Moniliella sp., Wallemia sp. and genera within the orden Mucorales were reported less recurrently. Despite finding a great fungal diversity, all of the studies focused their investigations on a small group of toxins: fumonisins (FBs), aflatoxins (AFs), deoxynivalenol (DON), zearalenone (ZEA), patulin (PAT), toxin T2 (T2) and ochratoxin (OT). Of the FBs, fumonisin B1 and fumonisin B2 presented higher incidence percentages, followed by fumonisin B3 . Of the AFs, the only one reported was aflatoxin B1. The mycotoxins DON, ZEA and OT were found with lower incidences, whereas PAT and T2 were not detected. Good management practices of the silo-bags are necessary to achieve a hermetically sealed environment, without exchange of gases and water with the external environment during the storage period. © 2022 Society of Chemical Industry.


Experiences of mothers of sexually abused children in North-West province, post disclosure.
Sexual violence against children is increasing at an alarming rate in South Africa. In 2010 the South African Police Service (SAPS) reported 21 538 rape cases of children under 18 years. In the North-West province (NWP) 5039 incidents of rape cases were reported in 2009. Mothers often experience emotional pain following child sexual abuse disclosure. It is seldom acknowledged that these mothers experience trauma and need support, post disclosure. The researcher has no known evidence of research conducted on the experiences of these mothers in NWP. The objective of the study was to explore and describe the experiences of mothers of sexually abused children post disclosure of the abuse. The research design was qualitative, exploratory, descriptive and contextual. Purposive sampling was used to select mothers of sexually abused children aged 23 to 59 years whose children ranged from 0 to 16 years. Permission to conduct the study was sought from the Provincial Department of Health and informed consent was obtained from the mothers. Interviews were conducted with a sample of n = 17 until data saturation. Data were collected through in-depth interviews using a voice recorder and field notes to enhance triangulation. Tesch's method of open coding was used to analyse data. Findings indicated that mothers experienced emotional pain post sexual abuse. They expressed shock, anger and guilt for not noticing the abuse. They showed significant depression as a result of lack of support by stakeholders. Mothers experienced secondary trauma that poses social and psychological challenges with far-reaching implications.


Chemistry and behavioral studies identify chiral cyclopropanes as selective α4β2-nicotinic acetylcholine receptor partial agonists exhibiting an antidepressant profile.
Despite their discovery in the early 20th century and intensive study over the last 20 years, nicotinic acetylcholine receptors (nAChRs) are still far from being well understood. Only a few chemical entities targeting nAChRs are currently undergoing clinical trials, and even fewer have reached the marketplace. In our efforts to discover novel and truly selective nAChR ligands, we designed and synthesized a series of chiral cyclopropane-containing α4β2-specific ligands that display low nanomolar binding affinities and excellent subtype selectivity while acting as partial agonists at α4β2-nAChRs. Their favorable antidepressant-like properties were demonstrated in the classical mouse forced swim test. Preliminary ADMET studies and broad screening toward other common neurotransmitter receptors were also carried out to further evaluate their safety profile and eliminate their potential off-target activity. These highly potent cyclopropane ligands possess superior subtype selectivity compared to other α4β2-nAChR agonists reported to date, including the marketed drug varenicline, and therefore may fully satisfy the crucial prerequisite for avoiding adverse side effects. These novel chemical entities could potentially be advanced to the clinic as new drug candidates for treating depression.


Metabolic Stability Assessment of New PARP Inhibitor Talazoparib Using Validated LC-MS/MS Methodology: In silico Metabolic Vulnerability and Toxicity Studies.
Talazoparib (BMN673) is a new poly(ADP-ribose) polymerase inhibitor that has been FDA approved for patients suffering from metastatic breast cancer with germline BRCA mutations. In the current study, an accurate and efficient liquid chromatography-tandem mass spectrometry (LC-MS/MS) analytical methodology was developed for TZB estimation in addition to its metabolic stability assessment. TZB and lapatinib (LAP) (which is chosen as an internal standard; IS) were separated using reversed phase elution system (Hypersil C18 column) with an isocratic mobile phase. The linearity range of the established method was 5-500 ng/mL (r2 ≥ 0.999) in the human liver microsomes (HLMs) matrix. Different parameters were calculated to confirm the method sensitivity (limit of quantification was 2.0 ng/mL), and reproducibility (intra- and inter-day precision and accuracy were below 3.1%) of our methodology. For evaluation of TZB metabolic stability in HLM matrix, intrinsic clearance (9.59 µL/min/mg) and in vitro half-life (72.7 mins) were calculated. TZB treatment discontinuations were reported due to adverse events and dose accumulation, so in silico metabolic vulnerability (experimental and in silico) and toxicity assessment (in silico) of TZB were performed utilizing P450 Metabolism and DEREK modules of StarDrop software. TZB is slowly metabolized by the liver. TZB was reported to be minimally metabolized by the liver that approved our outcomes. We do recommend that plasma levels be monitored in cases when talazoparib is used for a long period of time, since it is possible for TZB to bioaccumulate after multiple doses to toxic levels. According to our knowledge, the current method is considered the first LC-MS/MS methodology for evaluating TZB metabolic stability. Further drug discovery studies can be done depending on this concept allowing the designing of new series of compounds with more safety profile through reducing side effects and improving metabolic behavior.


Interactions between demography, genetics, and landscape connectivity increase extinction probability for a small population of large carnivores in a major metropolitan area.
The extinction vortex is a theoretical model describing the process by which extinction risk is elevated in small, isolated populations owing to interactions between environmental, demographic, and genetic factors. However, empirical demonstrations of these interactions have been elusive. We modelled the dynamics of a small mountain lion population isolated by anthropogenic barriers in greater Los Angeles, California, to evaluate the influence of demographic, genetic, and landscape factors on extinction probability. The population exhibited strong survival and reproduction, and the model predicted stable median population growth and a 15% probability of extinction over 50 years in the absence of inbreeding depression. However, our model also predicted the population will lose 40-57% of its heterozygosity in 50 years. When we reduced demographic parameters proportional to reductions documented in another wild population of mountain lions that experienced inbreeding depression, extinction probability rose to 99.7%. Simulating greater landscape connectivity by increasing immigration to greater than or equal to one migrant per generation appears sufficient to largely maintain genetic diversity and reduce extinction probability. We provide empirical support for the central tenet of the extinction vortex as interactions between genetics and demography greatly increased extinction probability relative to the risk from demographic and environmental stochasticity alone. Our modelling approach realistically integrates demographic and genetic data to provide a comprehensive assessment of factors threatening small populations.


Anisotropic sliding dynamics, peak effect, and metastability in stripe systems.
A variety of soft and hard condensed matter systems are known to form stripe patterns. Here we use numerical simulations to analyze how such stripe states depin and slide when interacting with a random substrate and with driving in different directions with respect to the orientation of the stripes. Depending on the strength and density of the substrate disorder, we find that there can be pronounced anisotropy in the transport produced by different dynamical flow phases. We also find a disorder-induced "peak effect" similar to that observed for superconducting vortex systems, which is marked by a transition from elastic depinning to a state where the stripe structure fragments or partially disorders at depinning. Under the sudden application of a driving force, we observe pronounced metastability effects similar to those found near the order-disorder transition associated with the peak effect regime for three-dimensional superconducting vortices. The characteristic transient time required for the system to reach a steady state diverges in the region where the flow changes from elastic to disordered. We also find that anisotropy of the flow persists in the presence of thermal disorder when thermally induced particle hopping along the stripes dominates. The thermal effects can wash out the effects of the quenched disorder, leading to a thermally induced stripe state. We map out the dynamical phase diagram for this system, and discuss how our results could be explored in electron liquid crystal systems, type-1.5 superconductors, and pattern-forming colloidal assemblies.


The Phenotypic Spectrum of Nephropathies Associated with Mutations in Diacylglycerol Kinase ε.
The recent discovery of mutations in the gene encoding diacylglycerol kinase ε (DGKE) identified a novel pathophysiologic mechanism leading to HUS and/or MPGN. We report ten new patients from eight unrelated kindreds with DGKE nephropathy. We combined these cases with all previously published cases to characterize the phenotypic spectrum and outcomes of this new disease entity. Most patients presented with HUS accompanied by proteinuria, whereas a subset of patients exhibited clinical and histologic patterns of MPGN without TMA. We also report the first two patients with clinical and histologic HUS/MPGN overlap. DGKE-HUS typically manifested in the first year of life but was not exclusively limited to infancy, and viral triggers frequently preceded HUS episodes. We observed signs of complement activation in some patients with DGKE-HUS, but the role of complement activation remains unclear. Most patients developed a slowly progressive proteinuric nephropathy: 80% of patients did not have ESRD within 10 years of diagnosis. Many patients experienced HUS remission without specific treatment, and a few patients experienced HUS recurrence despite complete suppression of the complement pathway. Five patients received renal allografts, with no post-transplant recurrence reported. In conclusion, we did not observe a clear genotype-phenotype correlation in patients with DGKE nephropathy, suggesting additional factors mediating phenotypic heterogeneity. Furthermore, the benefits of anti-complement therapy are questionable but renal transplant may be a feasible option in the treatment of patients with this condition.


Measures of Patient Dissatisfaction With Health Care in Polycystic Ovary Syndrome: Retrospective Analysis.
Polycystic ovary syndrome (PCOS) is a common reproductive and metabolic disorder in women; however, many clinicians may not be well versed in scientific advances that aid understanding of the associated reproductive, metabolic, and psychological abnormalities. Women with PCOS are dissatisfied with health care providers, the diagnostic process, and the initial treatment of PCOS and seek information through alternative sources. This has affected the patient-physician relationship by allowing medical information acquired through the internet, whether correct or not, to become accessible to patients and reshape their health care perspective. Patient dissatisfaction with health care providers regarding PCOS raises questions about the responsibilities of academic institutions to adequately train and maintain the competence of clinicians and government agencies to sufficiently support scientific investigation in this field. The primary aim was to examine internet searching behaviors of the public regarding PCOS vs another highly prevalent gynecologic disorder. The secondary aim was to explore satisfaction with health care among patients with PCOS and their internet use. The tertiary aim was to examine medical education in reproductive endocrinology and infertility (REI) during obstetrics and gynecology (Ob/Gyn) residency as a proxy for physician knowledge in this field. Google search trends and StoryBase quantified monthly Google absolute search volumes for search terms related to PCOS and fibroids (January 2004 to December 2017; United States). The reproductive disorder, fibroids, was selected as a comparison group because of its high prevalence among women. Between female groups, monthly absolute search volumes and their trends were compared. A Web-based questionnaire (June 2015 to March 2018) explored health care experiences and the internet use of women with PCOS. REI rotation information during Ob/Gyn residency in the United States was obtained from the Association of Professors of Gynecology and Obstetrics website. For PCOS (R=0.89; P<.01), but not fibroids (R=0.09; P=.25), monthly absolute search volumes increased significantly. PCOS-related monthly absolute search volumes (mean 384,423 searches, SD 88,756) were significantly greater than fibroid-related monthly absolute search volumes (mean 348,502 searches, SD 37,317; P<.05). PCOS was diagnosed by an Ob/Gyn in 60.9% (462/759) of patients, and 57.3% (435/759) of patients were dissatisfied with overall care. Among patients with PCOS, 98.2% (716/729) searched for PCOS on the Web but only 18.8% (143/729) of patients joined an online PCOS support group or forum. On average, Ob/Gyn residencies dedicated only 4% (2/43) of total block time to REI, whereas 5.5% (11/200) of such residencies did not offer any REI rotations. Over time, PCOS has been increasingly searched on the Web compared with another highly prevalent gynecologic disorder. Patients with PCOS are dissatisfied with their health care providers, who would benefit from an improved understanding of PCOS during Ob/Gyn residency training.


Use of ablation and ultrasonic aspiration at primary debulking surgery in advanced stage ovarian, fallopian tube, and primary peritoneal cancer.
Ovarian cancer patients with miliary disease have the lowest rates of complete surgical resection and poorest survival. Adjunct surgical techniques may potentially increase rates of complete surgical resection. No studies have evaluated the use of these techniques in primary debulking surgery for ovarian cancer patients with miliary disease. The aim of this study was to examine the use of adjunct surgical techniques during primary debulking surgery for patients with advanced epithelial ovarian, fallopian tube, and primary peritoneal cancer with miliary disease. Medical records of patients with International Federation of Gynecology and Obstetrics (FIGO) stages IIIC-IVB epithelial ovarian, fallopian tube, or primary peritoneal cancer with miliary disease undergoing primary debulking surgery from January 2010 to December 2014 were reviewed. Adjunct surgical techniques were defined as ultrasonic surgical aspiration, argon enhanced electrocautery, thermal plasma energy, and traditional electrocautery ablation. Patients undergoing surgery with and without these devices were compared with respect to demographics, operative characteristics, postoperative complications, residual disease, progression free survival and overall survival. A total of 135 patients with miliary disease underwent primary debulking surgery, of which 30 (22.2%) patients used adjunct surgical techniques. The most common devices were ultrasonic surgical aspiration (40%) and argon enhanced electrocautery (36.7%). The most common sites of use were diaphragm (63.3%), pelvic peritoneum (30%), bowel mesentery (20%), and large bowel serosa (20%). There were no differences in age, stage, primary site, histology, operative time, surgical complexity, or postoperative complications for patients operated on with or without these devices. Volume of residual disease was similar (0.1-1 cm: 60% with adjunct techniques versus 68.6% without; complete surgical resection: 16.7% with adjunct techniques versus 13.3% without; p=0.67). For patients with ≤1 cm residual disease, median progression free survival (15 versus 15 months, p=0.65) and median overall survival (40 versus 55 months, p=0.38) were also similar. Adjunct surgical techniques may be incorporated during primary debulking surgery for patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer with miliary disease; however, these do not improve the rate of optimal cytoreduction.


Comparison of dysferlin expression in human skeletal muscle with that in monocytes for the diagnosis of dysferlin myopathy.
Dysferlinopathies are caused by mutations in the dysferlin gene (DYSF). Diagnosis is complex due to the high clinical variability of the disease and because dysferlin expression in the muscle biopsy may be secondarily reduced due to a primary defect in some other gene. Dysferlin is also expressed in peripheral blood monocytes (PBM). Studying dysferlin in monocytes is used for the diagnosis of dysferlin myopathies. The aim of the study was to determine whether dysferlin expression in PBM correlates with that in skeletal muscle. Using western-blot (WB) we quantified dysferlin expression in PBM from 21 pathological controls with other myopathies in whom mutations in DYSF were excluded and from 17 patients who had dysferlinopathy and two mutations in DYSF. Results were compared with protein expression in muscle by WB and immunohistochemistry (IH). We found a good correlation between skeletal muscle and monocytes using WB. However, IH results were misleading because abnormal expression of dysferlin was also observed in 13/21 pathological controls. The analysis of dysferlin protein expression in PBM is helpful when: 1) the skeletal muscle IH pattern is abnormal or 2) when muscle WB can not be performed either because muscle sample is lacking or insufficient or because the muscle biopsy is taken from a muscle at an end-stage and it mainly consists of fat and fibrotic tissue.


[The role of occupational therapy in contexts of armed conflict and the post-conflict].
Objective To identify professional experiences of Occupational Therapy in Colombian and international contexts of armed conflict and post-conflict. Methods A qualitative systematic review of the literature between 2005-2014 in five analytical categories: professional experiences, problem situations, populations, theoretical frameworks, and procedures. Results 78 papers were retrieved. Colombian context: the models most used are human occupation and occupational performance; the most frequent problem is forced displacement. International context: 19 countries documented experiences; the Canadian model and the community-based rehabilitation model are most used; the main problem situations are forced displacement, refugee status, and attention to members of the armed forces. Both contexts highlight procedures such as artistic activities and interventions related to social welfare and social-inclusion. Conclusions Graduate these are the main source of Colombian experiences, though few are published; there are a few studies about victim population (demobilized). The rural sector as a typical scenario of armed conflict and a context of displacement have been seen as relevant. Frequent conceptual categories and practices have been introduced from the critical perspective of Occupational Therapy which reinforce the role of the professional in phenomena of social exclusion and violence, as a transformational agent that addresses the socio-political dimension of human occupation. These findings posit challenges for professionals and academics to publish, to work with populations (victims or not), to approach training and practice in rural contexts, and to recognize the role of the professional as an agent that transcends the public health dimension of human occupation.


Nutrition and cardiovascular health.
A multitude of studies have been published on the relationship between cardiovascular disease risk and a variety of nutrients, foods, and dietary patterns. Despite the well-accepted notion that diet has a significant influence on the development and prevention of cardiovascular disease, the foods considered healthy and harmful have varied over the years. This review aims to summarize the current scientific evidence on the cardioprotective effect of those foods and nutrients that have been considered healthy as well as those that have been deemed unhealthy at any given time in history. For this purpose, we reviewed the most recent literature using as keywords foods and nutrients (ie, meat, omega-3) and cardiovascular disease-related terms (ie, cardiovascular diseases, stroke). Emphasis has been placed on meta-analyses and Cochrane reviews. In general, there is a paucity of intervention studies with a high level of evidence supporting the benefits of healthy foods (ie, fruits and vegetables), whereas the evidence supporting the case against those foods considered less healthy (ie, saturated fat) seems to be weakened by most recent evidence. In summary, most of the evidence supporting the benefits and harms of specific foods and nutrients is based on observational epidemiological studies. The outcome of randomized clinical trials reveals a more confusing picture with most studies providing very small effects in one direction or another; the strongest evidence comes from dietary patterns. The current status of the relationship between diet and cardiovascular disease risk calls for more tailored recommendations based on genomic technologies.


Development and validation of a screening tool to predict the risk of chronic low back pain in patients presenting with acute low back pain: a study protocol.
Around 40% of people presenting to primary care with an episode of acute low back pain develop chronic low back pain. In order to reduce the risk of developing chronic low back pain, effective secondary prevention strategies are needed. Early identification of at-risk patients allows clinicians to make informed decisions based on prognostic profile, and researchers to select appropriate participants for secondary prevention trials. The aim of this study is to develop and validate a prognostic screening tool that identifies patients with acute low back pain in primary care who are at risk of developing chronic low back pain. This paper describes the methods and analysis plan for the development and validation of the tool. The prognostic screening tool will be developed using methods recommended by the Prognosis Research Strategy (PROGRESS) Group and reported using the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) statement. In the development stage, we will use data from 1248 patients recruited for a prospective cohort study of acute low back pain in primary care. We will construct 3 logistic regression models to predict chronic low back pain according to 3 definitions: any pain, high pain and disability at 3 months. In the validation stage, we will use data from a separate sample of 1643 patients with acute low back pain to assess the performance of each prognostic model. We will produce validation plots showing Nagelkerke R(2) and Brier score (overall performance), area under the curve statistic (discrimination) and the calibration slope and intercept (calibration). Ethical approval from the University of Sydney Ethics Committee was obtained for both of the original studies that we plan to analyse using the methods outlined in this protocol (Henschke et al, ref 11-2002/3/3144; Williams et al, ref 11638).


Stability of injection solutions of vitamin B1 Part 1: Influence of chelating agents.
The chelating agents EDTA, DTPA and HEDTA increase the stability of thiamine hydrochloride solutions. The stabilizing efficiency of HEDTA and DTPA is highly superior to that of EDTA. There is an optimum concentration of EDTA at which its stabilizing effect is maximum; beyond this concentration, the stability of the vitamin decreases gradually by increasing EDTA concentration. EDTA at a comparatively high concentration (10 mmole/1) catalyzes thiamine degradation. The stabilizing action of DTPA increases gradually as a function of its concentration. On the other hand, HEDTA in a very low concentration (0.5 mmole/1) affords a definite inhibitory effect on the rate of thiamine cleavage. However, increasing HEDTA concentration from 0.5 up to 3.0 mmole/1 does not increase its stabilizing efficiency. At HEDTA concentrations higher than 3 mmole/1, the stability of the vitamin increases gradually as a function of the chelating agent concentration.


Gait mechanics in patients with chronic obstructive pulmonary disease.
Chronic obstructive pulmonary disease (COPD) is characterized by the frequent association of disease outside the lung. The objective of this study was to determine the presence of biomechanical gait abnormalities in COPD patients compared to healthy controls while well rested and without rest. Patients with COPD (N = 17) and aged-matched, healthy controls (N = 21) walked at their self-selected pace down a 10-meter walkway while biomechanical gait variables were collected. A one-minute rest was given between each of the five collected trials to prevent tiredness (REST condition). Patients with COPD then walked at a self-selected pace on a treadmill until the onset of self-reported breathlessness or leg tiredness. Subjects immediately underwent gait analysis with no rest between each of the five collected trials (NO REST condition). Statistical models with and without covariates age, gender, and smoking history were used. After adjusting for covariates, COPD patients demonstrated more ankle power absorption in mid-stance (P = 0.006) than controls during both conditions. Both groups during NO REST demonstrated increased gait speed (P = 0.04), stride length (P = 0.03), and peak hip flexion (P = 0.04) with decreased plantarflexion moment (P = 0.04) and increased knee power absorption (P = 0.04) as compared to REST. A significant interaction revealed that peak ankle dorsiflexion moment was maintained from REST to NO REST for COPD but increased for controls (P < 0.01). Stratifying by disease severity did not alter these findings, except that step width decreased in NO REST as compared to REST (P = 0.01). Standardized effect sizes of significant effects varied from 0.5 to 0.98. Patients with COPD appear to demonstrate biomechanical gait changes at the ankle as compared to healthy controls. This was seen not only in increased peak ankle power absorption during no rest but was also demonstrated by a lack of increase in peak ankle dorsiflexion moment from the REST to the NO REST condition as compared to the healthy controls. Furthermore, a wider step width has been associated with fall risk and this could account for the increased incidence of falls in patients with COPD.


Impact of a Genetic Evaluation Initiative to Increase Access to Genetic Services for Adolescent and Young Adults at a Tertiary Cancer Hospital.
Purpose: Adolescents and young adults (AYAs) with cancer are at increased risk for inherited cancer predisposition syndromes. Genetic counseling (GC) is important for accurate risk assessment, diagnosis, and management of inherited cancers. Numerous barriers prevent AYA access to genetic services. This study describes outcomes of a genetic evaluation initiative (GEI) regarding utilization of genetic services among AYAs. Methods: To improve AYA access to GC, the AYA program at UT MD Anderson Cancer Center implemented GEI, a process for identifying and referring eligible patients for GC. We collected retrospective electronic medical record data between July 12, 2018 and July 12, 2019 to capture AYA's clinical characteristics, genetic referral, scheduled appointments, counseling, testing, and results. Results: In total, 516 AYAs were referred to the AYA clinic during the study period with a median age of first cancer diagnosis of 17 years. One hundred sixty-six AYAs were identified who would benefit from genetic evaluation, 57 (34.3%) of whom had previously undergone counseling. One hundred nine patients were recommended for referral to GC, and 64.2% (70/109) were referred by the AYA team. To date, 58.6% (41/70) met with a genetic counselor and 75.6% (31/41) completed genetic testing, which yielded 1 pathogenic, 2 uncertain, and 29 benign results. Conclusion: The GEI resulted in a 72.0% relative increase in the rate of GC utilization and represents a novel approach to increasing AYA patient access to cancer genetic services in this population.


Immunohistochemical evidence for the presence of melatonin in the pineal gland, the retina and the Harderian gland.
The presence of melatonin is demonstrated in the pineal gland, the retina and the Harderian gland in some mammalian and non-mammalian vertebrates, using a specific fluorescence labelled antibody technique. Four different potent antibodies against melatonin have been used and compared. In the pineal gland of hamsters, mice, rats and snakes, specific fluorescence, mostly restricted to the cytoplasm of the cells, is detected in pinealocytes. Fluorescence is also detected in the pineal organ of fishes, tortoises and lizards, but it has not been possible, from cryostat sections of fresh tissue, to assert which kind of cell is reacting (photoreceptor cells or interstitial ependymal cells). In the retina, fluorescence is almost exclusively restricted to the outer nuclear layer. In the Harderian gland of mammals and reptiles, fluorescence is localized in the secretory cells of the alveoli and mostly restricted to the cytoplasm surrounding the nucleus. These results are discussed in relation to the concept of melatonin synthesis at extrapineal sites independent of pineal production.


Experimental simulation of simultaneous vision.
To present and validate a prototype of an optical instrument that allows experimental simulation of pure bifocal vision. To evaluate the influence of different power additions on image contrast and visual acuity. The instrument provides the eye with two superimposed images, aligned and with the same magnification, but with different defocus states. Subjects looking through the instrument are able to experience pure simultaneous vision, with adjustable refractive correction and addition power. The instrument is used to investigate the impact of the amount of addition of an ideal bifocal simultaneous vision correction, both on image contrast and on visual performance. the instrument is validated through computer simulations of the letter contrast and by equivalent optical experiments with an artificial eye (camera). Visual acuity (VA) was measured in four subjects (AGE: 34.3 ± 3.4 years; spherical error: -2.1 ± 2.7 diopters [D]) for low and high contrast letters and different amounts of addition. The largest degradation in contrast and visual acuity (∼25%) occurred for additions around ±2 D, while additions of ±4 D produced lower degradation (14%). Low additions (1-2 D) result in lower VA than high additions (3-4 D). A simultaneous vision instrument is an excellent tool to simulate bifocal vision and to gain understanding of multifocal solutions for presbyopia. Simultaneous vision induces a pattern of visual performance degradation, which is well predicted by the degradation found in image quality. Neural effects, claimed to be crucial in the patients' tolerance of simultaneous vision, can be therefore compared with pure optical effects.


Binocular luminance summation in young kittens and adult strabismic cats.
Normal adult cats show a 35% increase in pupil diameter when one eye is illuminated and the other occluded, rather than when both eyes are illuminated. Young kittens show significantly less binocular luminance summation than adult cats (14%). Since these kittens also show a significantly reduced pupillary response to luminance decrements, the postnatal development of binocular luminance summation reflects an increase in pupillary motility, rather than a development of binocular function. Binocular luminance summation is much reduced in esotropic cats (6%), but not in exotropic cats (33%). This finding casts doubts on the usefulness of binocular luminance summation as a measure of binocular function.


Patient responsibility for medical decision making and risky treatment options.
Studies have shown that increasing patient participation in decision making decreases utilization of risky procedures. It has been demonstrated that risk perception is increased under conditions that emphasize volition, or the act of choosing. The objective of this study was to examine whether emphasizing volition increases patients' risk perception and decreases their willingness to accept risk. Consecutive patients attending outpatient clinic appointments viewed a video in which a physician described the availability of a new medication associated with a rare risk of a serious side effect. Patients' willingness to accept treatment and worry about the risk of the serious side effect were measured under 2 different conditions: one that minimized patient involvement and the one that maximized patient involvement in the decision-making process. The willingness of the subject to take the proposed medication was lower (mean +/- SD 4.2 +/- 3.7 versus 5.3 +/- 3.7; P < 0.001) and their worry about the risk of the adverse event was greater in the high compared with the low involvement condition (mean +/- SD 6.1 +/- 3.7 versus 5.5 +/- 3.8; P < 0.001). Increasing patient responsibility in medical decision making may decrease the patient's willingness to accept risky treatment options.


Does early antipsychotic response predict long-term treatment outcome?
Early antipsychotic response within the first 2-3 weeks of treatment can predict short-term outcomes after several months. We conducted the current study to determine whether the predictive value of early antipsychotic response persists throughout long-term treatment over multiple years. In this observational study, we conducted follow-up assessments of 64 patients with first-episode psychosis an average of 25 months after they began antipsychotic treatment. Patients were initially randomized to receive haloperidol or olanzapine, but treatment after the acute hospitalization period was not controlled. Regression analyses were used to determine whether early improvement on the Brief Psychiatric Rating Scale at 2 or 3 weeks predicted longer term improvement at follow-up. We conducted secondary analyses to determine whether early response could predict extrapyramidal side effects at follow-up. Early response to haloperidol at 2 weeks predicted Brief Psychiatric Rating Scale improvement on longer term follow-up (p = .002). Longer term improvement was not predicted by early response to olanzapine at 2 weeks (p = .726) or 3 weeks (p = .541). Rates of extrapyramidal side effects did not differ between treatment groups and were not predicted by early response. These results demonstrate the long-term prognostic value of early haloperidol response. The predictive value of early olanzapine response may be less robust.


Percutaneous transluminal coronary rotary ablation with Rotablator (European experience).
This study reports the results from 3 European centers using rotary ablation with Rotablator, a device that is inserted into the coronary artery and removes atheroma by grinding it into millions of tiny fragments. Rotary ablation was performed in 129 patients. Primary success (reduction in percent luminal narrowing greater than 20%, residual stenosis less than 50%, without complications) was achieved by rotary angioplasty alone in 73 patients (57%). An additional 38 patients (29%) had successful adjunctive balloon angioplasty. Thus primary success was achieved in 111 patients (86%) at the end of the procedure. Acute occlusion occurred in 10 patients (7.7%). Recanalization was achieved by balloon angioplasty in 7: urgent bypass grafting was undertaken in 2. Q-wave and non-Q-wave myocardial infarction occurred in 3 and 7 patients, respectively. No deaths occurred. Follow-up angiography was performed in 74 patients (60%). Restenosis, defined as the recurrence of significant luminal narrowing (greater than 50%) occurred in 17 of 37 patients (46%) who underwent rotary ablation alone, and 11 of 37 patients (30%) who had adjunctive balloon angioplasty. The overall angiographic restenosis rate was 37.8%. In conclusion, rotary ablation is technically feasible, and relatively safe in the coronary circulation. The low primary success rate reflects the limited size of the device, which can be introduced through available guiding catheters, and limits the use of rotary ablation as a stand-alone procedure to lesions in small arteries or in distal locations. No reduction in restenosis was seen, but the role of this device combined with balloon angioplasty in larger arteries needs to be further defined.


Critical Comparison of Biomembrane Force Fields: Protein-Lipid Interactions at the Membrane Interface.
Molecular dynamics (MD) simulations offer the possibility to study biological processes at high spatial and temporal resolution often not reachable by experiments. Corresponding biomolecular force field parameters have been developed for a wide variety of molecules ranging from inorganic ligands and small organic molecules over proteins and lipids to nucleic acids. Force fields have typically been parametrized and validated on thermodynamic observables and structural characteristics of individual compounds, e.g. of soluble proteins or lipid bilayers. Less strictly, due to the added complexity and missing experimental data to compare to, force fields have hardly been tested on the properties of mixed systems, e.g. on protein-lipid systems. Their selection and combination for mixed systems is further complicated by the partially differing parametrization strategies. Additionally, the presence of other compounds in the system may shift the subtle balance of force field parameters. Here, we assessed the protein-lipid interactions as described in the four atomistic force fields GROMOS54a7, CHARMM36 and the two force field combinations Amber14sb/Slipids and Amber14sb/Lipid14. Four observables were compared, focusing on the membrane-water interface: the conservation of the secondary structure of transmembrane proteins, the positioning of transmembrane peptides relative to the lipid bilayer, the insertion depth of side chains of unfolded peptides absorbed at the membrane interface, and the ability to reproduce experimental insertion energies of Wimley-White peptides at the membrane interface. Significant differences between the force fields were observed that affect e.g. membrane insertion depths and tilting of transmembrane peptides.


Polarized light scattered from monodisperse randomly oriented nonspherical aerosol particles: measurements.
Measurements of polarized light scattered from monodisperse nonspherical randomly oriented aerosol particles are presented along with Mie theoretical results for spheres of approximately the same cross sectional area. For slightly nonspherical particles of sodium chloride and potassium sulfate with size parameter (defined as the ratio of the particle circumference to the wavelength) greater than about five, the intensity of light scattered is generally more than as predicted by Mie theory in the forward scattering lobe, but less at nonforward angles. For particles with size parameter less than five, the Mie results more closely match the measurements. Measured angular scattering patterns for randomly oriented particles are smoother than the Mie theoretical results and are nearly the same for salt and potassium sulfate particles of the same size. Measurements of particle depolarization are nearly independent of scattering angle.


Pleural disease during treatment with bromocriptine in patients previously exposed to asbestos.
Bromocriptine, which is used in the treatment of Parkinson's disease, can cause adverse pleuropulmonary reactions. Exposure to asbestos can result in similar lesions. Fifteen patients with former exposure to asbestos, who developed pleural fibrosis after treatment with bromocriptine, were observed independently in Sweden (11 patients) and Australia (four patients). The patients complained of malaise, often associated with weight loss, dyspnoea, and a disturbing cough. Laboratory values included increased erythrocyte sedimentation rate and a low haemoglobin level. Lung function tests showed a restrictive lung function defect. Chest radiographs showed bilateral pleural fibrosis, with small amounts of fluid in some cases. Soon after bromocriptine was withdrawn, the patients improved clinically, and the laboratory values returned to normal. However, in most cases, pleural fibrosis and a restrictive lung function defect persisted to some extent. In conclusion, in patients who develop pleuropulmonary fibrosis whilst being treated with bromocriptine, former exposure to asbestos should be investigated. Conversely, when pleural changes develop in a patient on bromocriptine and with prior exposure to asbestos, the possible causative role of the drug should be discussed. Special follow-up may be indicated when bromocriptine is planned in a patient with previous asbestos exposure, and if symptoms or signs of pleural fibrosis develop, bromocriptine withdrawal should be considered.


Intracellular pH and glutathione levels in rabbit corneal endothelium following storage in moist chamber and MK medium.
Rabbit corneas were stored for up to 14 days at 4 C either as the whole eye in a moist chamber or as the isolated cornea in MK medium with HEPES buffer. The intracellular pH, the glutathione content, and its oxidation state were determined in the endothelial cells of fresh and stored tissue. The endothelial pH was found to be unchanged following storage of up to 7 days by either method, but after 14 days the pH rose slightly but statistically significantly in corneas stored by both techniques. The intracellular pH was similar in endothelia of those corneas stored in MK medium and of those stored as the whole eye in a moist chamber, for all time periods studied. The intracellular total and percent oxidized glutathione of the endothelium were increased by 50 and 180%, respectively, following 7 days of moist chamber storage. Over this time period there was a 50-fold increase in total glutathione content of the aqueous humor in the stored eyes. In contrast, corneas stored in MK medium for 7 days maintained intracellular total glutathione at levels similar to those of fresh corneas. A gradual but constant decrease in percent oxidized glutathione was observed with increasing length of storage. In terms of pH and glutathione content, the MK medium provided a much more stable environment for the stored cornea than did the aqueous humor in the stored eye.


Cavitary pulmonary coccidioidomycosis: pathologic and clinical correlates of disease.
Cavitary pulmonary coccidioidomycosis is a difficult diagnosis to establish due to the poor sensitivity of serological tests and rarity of culture from sputum. A pathologic and clinical analysis was performed of 21 consecutive patients with surgically resected cavities that proved to be coccidioidomycosis. Ten patients (48%) had serological evidence of Coccidioides infection, and 1 patient cultured Coccidioides spp. from sputum. The definitive diagnosis of coccidioidomycosis was made in the remaining 10 patients (48%) upon microscopic examination of tissue. The pleura showed fibrous pleuritis in 7 patients (33%) and eosinophilic pleuritis in 4 cases (19%); granulomas without microorganisms were demonstrated in 4 cases (19%). The cavity wall showed chronic inflammation and occasional giant cells but no granulomas and no microorganisms. The cavity contents included a mycetoma in 6 cases (28%); the cavity lining showed neutrophils and caseous necrosis; Coccidioides hyphae were present in 13 (62%) and spherules in 16 (76%) cases but often were rare. Adjacent lung showed lymphoid hyperplasia with chronic bronchiolitis in all cases; satellite granulomas with diagnostic spherules were variably present. The histopathology of cavitary coccidioidomycosis is strikingly variable depending on what area is sampled by biopsy, and microorganisms may be rare. This may explain the high rate of failure of diagnosis by fine needle aspiration and bronchoalveolar lavage. Pathologists in nonendemic areas must be aware of these findings, as this disease is now diagnosed worldwide.


Mesoporous starch aerogels production as drug delivery matrices: synthesis optimization, ibuprofen loading, and release property.
The aim of this work was to prepare biodegradable starch aerogels as drug carriers. The effective parameters in the synthesis and the optimal values of these parameters were determined using Minitab experimental design software. Ibuprofen was selected as a model drug for the dissolution study and loaded into optimized aerogel during the last solvent exchange step. The Fourier Transform Infrared Spectroscopy (FTIR) analysis showed that ibuprofen has been successfully loaded into the aerogel matrix without any effect on the aerogel nature. The drug loading was calculated to be 29%. The isotherm of ibuprofen adsorption into aerogels matrices followed from the Freundlich isotherm. The in vitro release tests of crystalline ibuprofen and ibuprofen-loaded potato starch aerogel were investigated with simulated gastric and intestinal fluids in USP 2 apparatus. It was shown that the dissolution rate of ibuprofen could be dramatically changed. Also, an improvement in the dissolution rate of ibuprofen was achieved by performing the dissolution test first in the gastric medium for 120 min and then in the intestinal medium for up to 270 min. A higher release rate (100%) was observed at the end of the in vitro experiment.


Sperm donors versus long-term mates: a comparison of preferences of heterosexual and lesbian women.
The present study aimed to explore whether lesbian women's preferences for a sperm donor or a long-term mate show a pattern similar to those of heterosexual women. Three hundred and eighty-three donor insemination patients, of whom 278 were heterosexual and 105 were lesbian, completed a questionnaire comprising a series of 35 traits and rated the importance of each trait in a sperm donor and again in a long term mate. Results showed that traits relating to socioeconomic status, genetic background and general health, physical appearance, and personality were rated by lesbian women as more important in a long-term mate than in a sperm donor. It was further found that both heterosexual and lesbian women attached higher importance to the socioeconomic status, personality and physical appearance of the long-term mate than of the sperm donor; heterosexual women attached similar importance to the genes and health of a long-term mate and a sperm donor, while lesbian women attached greater importance to the genetic background and general health of the sperm donor than those of a long-term mate. The implications and interpretations of the findings are discussed in light of Trivers' parental investment theory.


Factors influencing the activity of succinate dehydrogenase in membrane preparations from Micrococcus lysodeikticus.
1. Some properties of succinate dehydrogenase [succinate-(acceptor) oxidoreductase, EC 126.96.36.199] in membrane preparations from Micrococcus lysodeikticus (N.C.T.C. 2665) were investigated. 2. In the spectrophotometric assay system adopted the reaction velocity was shown to be proportional to the amount of membrane added. Dichlorophenol-indophenol, reduced photochemically in the presence of phenazine methosulphate, or enzymically by the membrane-bound enzyme, was shown to undergo reoxidation in the dark. 3. The membrane-bound enzyme was found to be inactivated at temperatures above 10 degrees C. 4. The specific activity of membrane-bound succinate dehydrogenase was found to increase between two- and three-fold in diluted membrane preparations equilibrated at 0 degrees C for 6h. Membranes treated with sodium deoxycholate showed no enzyme activation on dilution but displayed maximal activity, all activity being sedimentable at 103000g. The increase in specific activity observed on dilution could be partially inhibited by fixation with glutaraldehyde, or by the presence of bovine serum albumin. 5. The addition of Mg(2+) or Ca(2+) ions to membrane suspensions caused an overall depression of enzyme activity. 6. The results suggest the presence of an ;inhibitor' that affects the expression of membrane bound succinate dehydrogenase activity.


Multi-area visuotopic map complexes in macaque striate and extra-striate cortex.
We propose that a simple, closed-form mathematical expression-the Wedge-Dipole mapping-provides a concise approximation to the full-field, two-dimensional topographic structure of macaque V1, V2, and V3. A single map function, which we term a map complex, acts as a simultaneous descriptor of all three areas. Quantitative estimation of the Wedge-Dipole parameters is provided via 2DG data of central-field V1 topography and a publicly available data set of full-field macaque V1 and V2 topography. Good quantitative agreement is obtained between the data and the model presented here. The increasing importance of fMRI-based brain imaging motivates the development of more sophisticated two-dimensional models of cortical visuotopy, in contrast to the one-dimensional approximations that have been in common use. One reason is that topography has traditionally supplied an important aspect of "ground truth," or validation, for brain imaging, suggesting that further development of high-resolution fMRI will be facilitated by this data analysis. In addition, several important insights into the nature of cortical topography follow from this work. The presence of anisotropy in cortical magnification factor is shown to follow mathematically from the shared boundary conditions at the V1-V2 and V2-V3 borders, and therefore may not causally follow from the existence of columnar systems in these areas, as is widely assumed. An application of the Wedge-Dipole model to localizing aspects of visual processing to specific cortical areas-extending previous work in correlating V1 cortical magnification factor to retinal anatomy or visual psychophysics data-is briefly discussed.


HDAC1, a histone deacetylase, forms a complex with Hus1 and Rad9, two G2/M checkpoint Rad proteins.
HDAC1 is a member of the histone deacetylase family, which plays an important role in modulating the eukaryotic chromatin structure. Numerous studies have demonstrated its involvement in transcription and in tumorigenesis. To better understand the functions and regulation of HDAC1, a yeast two-hybrid screening approach was chosen to identify novel interactions involving HDAC1. Human HDAC1 was found to interact specifically in yeast, mammalian cells, and in vitro with the human Hus1 gene product, whose Schizosaccharomyces pombe homolog has been implicated in G(2)/M checkpoint control. Both HDAC1 and Hus1 proteins localize to the nuclei. Furthermore, HDAC1 and Hus1 were found to exist in a complex with Rad9, a known Hus1-interacting factor. In addition, bioinformatics analysis of the protein sequences of Hus1, Rad1, and Rad9, three checkpoint Rad proteins that form a complex, revealed that they all contain a putative proliferating cell nuclear antigen (PCNA) fold, raising the possibility that these factors may bind to DNA in a PCNA-like ring structure. The results reported in this study strongly suggest a novel pathway involving HDAC1 in G(2)/M checkpoint control through the interaction with a functional Rad complex that may utilize a PCNA-like structure. Therefore, physically and functionally similar apparatus may function during G(2)/M checkpoint and DNA replication.


Therapies in muscular dystrophy: current concepts and future prospects.
In the fast moving field of muscular dystrophy, therapeutic matters are now high on the agenda. Despite little progress made in the understanding of the exact pathogenesis, hopes have been raised with the advent of molecular medicine applied to such disorders. A constellation of techniques or therapeutic solutions are now available, but very few have reached the clinical stage. Gene therapy, cell therapy and pharmacological therapy look more promising, but their clinical application may still take years. We review the various alternatives and suggest that some of them might be used in combination.


Lysobacter niabensis sp. nov. and Lysobacter niastensis sp. nov., isolated from greenhouse soils in Korea.
Two bacterial strains, designated GH34-4(T) and GH41-7(T), were isolated from greenhouse soil cultivated with cucumber. The bacteria were strictly aerobic, Gram-negative, rod-shaped and oxidase- and catalase-positive. 16S rRNA gene sequence analysis indicated that these strains belong to the genus Lysobacter within the Gammaproteobacteria. Strain GH34-4(T) showed highest sequence similarity to Lysobacter yangpyeongensis GH19-3(T) (97.5 %) and Lysobacter koreensis Dae16(T) (96.4 %), and strain GH41-7(T) showed highest sequence similarity to Lysobacter antibioticus DSM 2044(T) (97.5 %), Lysobacter enzymogenes DSM 2043(T) (97.5 %) and Lysobacter gummosus ATCC 29489(T) (97.4 %). Levels of DNA-DNA relatedness indicated that strains GH34-4(T) and GH41-7(T) represented species clearly different from L. yangpyeongensis, L. antibioticus, L. enzymogenes and L. gummosus. The major cellular fatty acids of strains GH34-4(T) and GH41-7(T) were iso-C(16 : 0), iso-C(15 : 0) and iso-C(17 : 1)omega9c, and the major isoprenoid quinone was Q-8. The DNA G+C contents of GH34-4(T) and GH41-7(T) were 62.5 and 66.6 mol%, respectively. On the basis of the polyphasic taxonomic data presented, it is evident that each of these strains represents a novel species of the genus Lysobacter, for which the names Lysobacter niabensis sp. nov. (type strain GH34-4(T)=KACC 11587(T)=DSM 18244(T)) and Lysobacter niastensis sp. nov. (type strain GH41-7(T)=KACC 11588(T)=DSM 18481(T)) are proposed.


In vivo and in vitro degradation of poly[(50)/(50) ((85)/(15)(L)/(D))LA/epsilon-CL], and the implications for the use in nerve reconstruction.
Nerve guides can be used for the reconstruction of peripheral nerve defects. After serving their function, nerve guides should degrade. p[(50)/(50) ((85)/(15)(L)/(D))LA/epsilon-CL] degrades completely within 1 year without the formation of a slow degrading crystalline fraction. Although the tensile strength (TS) of a p[(50)/(50) ((85)/(15)(L)/(D))LA/epsilon-CL] nerve guide is negligible after 2 months, nerve regeneration across a 1-cm gap in the sciatic nerve of the rat is faster and qualitatively better than after reconstruction using autologous nerve grafts. During degradation p[(50)/(50) ((85)/(15)(L)/(D))LA/epsilon-CL] swells, especially during the first 3 months. This can have a negative influence on the regenerating nerve. p[(50)/(50) ((85)/(15)(L)/(D))LA/epsilon-CL] nerve guides could only be used in the clinical situation in case of short nerve gaps (several mm) in small nerves (for instance digital nerves). Refinements will be needed to successfully reconstruct longer nerve gaps (several cm).


Polymorphous Low-Grade Neuroepithelial Tumor of the Young: A Case Report with Genomic Findings.
Polymorphous low-grade neuroepithelial tumor of the young (PLNTY) is a recently recognized epileptogenic neuroepithelial tumor. Despite its distinctiveness, its polymorphous histology and the nature of its oligodendrocyte-like cells remain unclear. A 30-year-old, right-handed man was diagnosed with intractable epilepsy since 22 years of age. Magnetic resonance imaging revealed T2 signal hyperintensity and corresponding T1 signal hypointensity within the subcortical white matter of the right middle temporal gyrus. Positron emission tomography scan demonstrated hypometabolism in the right anterior temporal region. Electroencephalography and stereo-electroencephalography monitoring localized seizures to the right temporal lobe, allowing the patient to undergo right temporal lobectomy. Histologic sections demonstrated cortical dysplasia, white matter heterotopia, and hippocampal reactive gliosis without neuronal loss. Interestingly, an approximately 6-mm subcortical neoplasm was identified in the temporal lobectomy. It was composed of well-differentiated oligodendroglial-like cells but exhibited mild-to-moderate nuclear variability and pleomorphism, and mild infiltration into the overlying cortex without perineuronal satellitosis. No mitotic activity, microvascular proliferation, or necrosis was identified, and Ki-67 labeling index was less than 1%. The tumor was diffusely CD34 positive with moderate glial fibrillary acidic protein and retained ATRX staining, and demonstrated the presence of the BRAF V600E mutation. The tumor was negative for reticulin condensation, synaptophysin, SMI31, neuronal nuclei immunostains, and both the IDH1 mutation and 1p19q codeletion. Overall histologic findings were most consistent with PLNTY. The correct diagnosis of PLNTY and its distinction from closely resembling low-grade neuroepithelial tumors is important. We hope our proposed diagnostic features will aid in its proper diagnosis and management.


Acute perilunate dislocation in a pediatric patient.
Lunate and perilunate dislocations are rare in children, but should be suspected in patients with significant wrist swelling and decreased range of motion after trauma or falls on an outstretched hand.


Gender differences in trunk and pelvic kinematics during prolonged ergometer rowing in adolescents.
The trunk and pelvis kinematics of 20 healthy male and female adolescent rowers were recorded during an ergometer trial using an electromagnetic tracking system (Fastrak). The kinematics of each drive phase were collected during the 1st and 20th minute, respectively. The mean and range of the kinematics, stroke rate and stroke length were compared between genders and over time. Male rowers postured their pelvis with more posterior tilt and their thoracic spine in more flexion than female rowers (P < .05). Both genders postured their pelvis in more posterior pelvic rotation and upper trunk in more flexion over time. Male rowers were found to have a significantly shorter drive phase than female rowers (P = .001). Differences in trunk and pelvic kinematics between adolescent male and female rowers suggest potentially various mechanisms for biomechanical stress. Assessment and training of rowers should take gender differences into consideration.


A Fenchone Derivative Effectively Abrogates Joint Damage Following Post-Traumatic Osteoarthritis in Lewis Rats.
In a previous report, we have identified the cannabinoid receptor 2 (CB2) agonist HU308 to possess a beneficial effect in preventing age and trauma-induced osteoarthritis (OA) in mice. The effects of HU308 were largely related to the capacity of this compound to induce cartilage anabolism which was dependent on the CREB/SOX9 axis, and exhibited pro-survival and pro-proliferative hallmarks of articular cartilage following treatment. Here, we utilized the novel cannabinoid-fenchone CB2 agonists (1B, 1D), which were previously reported to render anti-inflammatory effects in a zymosan model. Initially, we assessed the selectivity of CB2 using a Gs-protein receptor cAMP potency assay, which was also validated for antagonistic effects dependent on the Gi-protein receptor cAMP pathway. Based on EC50 values, 1D was selected for a zymosan inflammatory pain model. Next, 1D was administered in two doses intra-articularly (IA), in a post-traumatic medial meniscal tear (MMT, Lewis rats) model, and compared to sham, vehicle, and a positive control consisting of fibroblast growth factor 18 (FGF18) administration. The histopathological assessment was carried out according to the Osteoarthritis Research Society International (OARSI) guidelines for rat models following 28 days post-MMT. The G protein receptor assays confirmed that both 1B and 1D possess CB2 agonistic effects in cell lines and in chondrocytes. Co-administering a CB2 antagonists to 25 mg/kg 1D in a paw inflammatory pain model abolished 1D-related anti-swelling effect and partially abolishing its analgesic effects. Using an MMT model, the high dose (i.e., 24 µg) of 1D administered via IA route, exhibited reduced cartilage damage. Particularly, this dose of 1D exhibited a 30% improvement in cartilage degeneration (zonal/total tibial scores) and lesion depth ratios (44%), comparable to the FGF18 positive control. Synovitis scores remained unaffected and histopathologic evaluation of subchondral bone damage did not suggest that 1D treatment changed the load-bearing ability of the rats. Contrary to the anabolic effect of FGF18, synovial inflammation was observed and was accompanied by increased osteophyte size. The structural histopathological analysis supports a disease-modifying effect of IA-administered 1D compound without any deleterious effects on the joint structure.


Emergency appendicectomy during COVID-19 pandemic - A single UK centre experience.
Background - In December 2019 following an outbreak of Novel coronavirus infection (COVID-19) in Wuhan, China, it spread rapidly overwhelming the healthcare systems globally. With little knowledge of COVID-19 virus, very few published reports on surgical outcomes; hospitals stopped elective surgery, whilst emergency surgery was offered only after exhausting all conservative treatment modalities. This study presents our experience of outcomes of emergency appendectomies performed during the pandemic. Methods - Prospectively we collected data on 132 patients in peak pandemic period from 1st March to 5th June 2020 and data compared with 206 patients operated in similar period in 2019. Patient demographics, presenting symptoms, pre-operative events, investigations, surgical management, postoperative outcomes and complications were analysed. Results - Demographics and ASA grades of both cohorts were comparable. In study cohort 84.4% and 96.7% in control cohort had laparoscopic appendicectomy. Whilst the study cohort had 13.6% primary open operations, control cohort had 5.3%. Mean length of stay and early post-operative complications (<30 days) were similar in both cohorts apart from surgical site infections (p = 0.02) and one mortality in study cohort. Conclusion - In these overwhelming pandemic times, although conservative treatment of acute appendicitis is an option, a proportion of patients will need surgery. Our study shows that with careful planning and strict theatre protocols, emergency appendicectomy can be safely offered with minimal risk of spreading COVID-19 infection. These observations warrant further prospective randomised studies. Keywords - appendicectomy, COVID-19, Coronavirus, emergency surgery, laparoscopy.


The impact of macromastia on adolescents: a cross-sectional study.
To determine the physical and psychosocial impact of macromastia on adolescents considering reduction mammaplasty in comparison with healthy adolescents. The following surveys were administered to adolescents with macromastia and control subjects, aged 12 to 21 years: Short-Form 36v2, Rosenberg Self-Esteem Scale, Breast-Related Symptoms Questionnaire, and Eating-Attitudes Test-26 (EAT-26). Demographic variables and self-reported breast symptoms were compared between the 2 groups. Linear regression models, unadjusted and adjusted for BMI category (normal weight, overweight, obese), were fit to determine the effect of case status on survey score. Odds ratios for the risk of disordered eating behaviors (EAT-26 score ≥ 20) in cases versus controls were also determined. Ninety-six subjects with macromastia and 103 control subjects participated in this study. Age was similar between groups, but subjects with macromastia had a higher BMI (P = .02). Adolescents with macromastia had lower Short-Form 36v2 domain, Rosenberg Self-Esteem Scale, and Breast-Related Symptoms Questionnaire scores and higher EAT-26 scores compared with controls. Macromastia was also associated with a higher risk of disordered eating behaviors. In almost all cases, the impact of macromastia was independent of BMI category. Macromastia has a substantial negative impact on health-related quality of life, self-esteem, physical symptoms, and eating behaviors in adolescents with this condition. These observations were largely independent of BMI category. Health care providers should be aware of these important negative health outcomes that are associated with macromastia and consider early evaluation for adolescents with this condition.


Comparative responsiveness of pain measures in cancer patients.
Brief measures to assess and monitor pain in cancer patients are available, but few head-to-head psychometric comparisons of different measures have been reported. Baseline and 3-month data were analyzed from 274 patients enrolled in the Indiana Cancer Pain and Depression (INCPAD) trial. Participants completed the Brief Pain Inventory (BPI), the PEG (a 3-item abbreviated version of the BPI), the short form (SF)-36 pain scale, and a pain global rating of change measure. The global rating was used as the criterion for standardized response mean and receiver operating characteristic curve analyses. To assess responsiveness to the trial intervention, we evaluated standardized effect size statistics stratified by trial arm. All measures were responsive to global improvement, discriminated between participants with and without improvement, and detected a significant intervention treatment effect. Short and longer measures were similarly responsive. Also, composite measures that combined pain severity and interference into a single score (BPI total, PEG, SF-36 pain) performed comparably to separate measures of each domain (BPI severity and BPI interference). Pain measures as brief as 2 or 3 items that provide a single score are responsive in patients with cancer-related pain. Ultra-brief measures offer a valid and efficient means of assessing and monitoring pain for the clinical management as well as research of cancer-related pain.


Guidelines for sentinel node biopsy and lymphatic mapping of patients with breast cancer.
To define preliminary guidelines for the use of lymphatic mapping techniques in patients with breast cancer. Lymphatic mapping techniques have the potential of changing the standard of surgical care of patients with breast cancer. Four hundred sixty-six consecutive patients with newly diagnosed breast cancer underwent a prospective trial of intraoperative lymphatic mapping using a combination of vital blue dye and filtered technetium-labeled sulfur colloid. A sentinel lymph node (SLN) was defined as a blue node and/or a hot node with a 10:1 ex vivo gamma probe ratio of SLN to non-SLN. All SLNs were bivalved, step-sectioned, and examined with routine hematoxylin and eosin (H&E) stains and immunohistochemical stains for cytokeratin. A cytokeratin-positive SLN was defined as any SLN with a defined cluster of positive-staining cells that could be confirmed histologically on H&E sections. Fine-needle aspiration (FNA) or stereotactic core biopsy was used to diagnose 195 of the 422 patients (46.2%) with breast cancer; 227 of 422 patients (53.8%) were diagnosed by excisional biopsy. The SLN was successfully identified in 440 of 466 patients (94.4%). Failure to identify an SLN to the axilla intraoperatively occurred in 26 of 466 patients (5.6%). In all patients who failed lymphatic mappings, a complete axillary dissection was performed, and metastatic disease was documented in 4 of 26 (15.4%) of these patients. Of the 26 patients who failed lymphatic mapping, 11 of 227 (4.8%) were diagnosed by excisional biopsy and 15 of 195 (7.7%) were diagnosed by FNA or stereotactic core biopsy. Of interest, there was only one skip metastasis (defined as a negative SLN with higher nodes in the chain being positive) in a patient with prior excisional biopsy. A mean of 1.92 SLNs were harvested per patient. Twenty percent of the SLNs removed were positive for metastatic disease in 105 of 440 (23.8%) of the patients. Descriptive information on 844 SLNs was evaluated: 339 of 844 (40.2%) were hot, 272 of 844 (32.2%) were blue, and 233 of 844 (27.6%) were both hot and blue. At least one positive SLN was found in 4 of 87 patients (4.6%) with noninvasive (ductal carcinoma in situ) tumors. A greater incidence of positive SLNs was found in patients who had invasive tumors of increasing size: 18 of 112 patients (16%) with tumor size between 0.1 mm and 1 cm had positive SLNs. However, a significantly greater percentage of patients (43 of 131 [32.8%] with tumor size between 1 and 2 cm and 31 of 76 [40.8%] with tumor size between 2 and 5 cm) had positive SLNs. The highest incidence of positive SLNs was seen with patients of tumor size greater than 5 cm; in this group, 9 of 12 (75%) had a positive SLN (p < 0.001). This study demonstrates that accurate SLN identification was obtained when all blue and hot lymph nodes were harvested as SLNs. Therefore, lymphatic mapping and SLN biopsy is most effective when a combination of vital blue dye and radiolabeled sulfur colloid is used. Furthermore, these data demonstrate that patients with ductal carcinoma in situ or small tumors exhibit a low but significant incidence of metastatic disease to the axillary lymph nodes and may benefit most from selective lymphadenectomy, avoiding the unnecessary complications of a complete axillary lymph node dissection.


Microbial warfare and the evolution of symbiosis.
Cooperative symbionts enable their hosts to exploit a diversity of environments. A low genetic diversity (high relatedness) between the symbionts within a host is thought to favour cooperation by reducing conflict within the host. However, hosts will not be favoured to transmit their symbionts (or commensals) in costly ways that increase relatedness, unless this also provides an immediate fitness benefit to the host. We suggest that conditionally expressed costly competitive traits, such as antimicrobial warfare with bacteriocins, could provide a relatively universal reason for why hosts would gain an immediate benefit from increasing the relatedness between symbionts. We theoretically test this hypothesis with a simple illustrative model that examines whether hosts should manipulate relatedness, and an individual-based simulation, where host control evolves in a structured population. We find that hosts can be favoured to manipulate relatedness, to reduce conflict between commensals via this immediate reduction in warfare. Furthermore, this manipulation evolves to extremes of high or low vertical transmission and only in a narrow range is partly vertical transmission stable.


Current Epigenetic Insights in Kidney Development.
The kidney is among the best characterized developing tissues, with the genes and signaling pathways that regulate embryonic and adult kidney patterning and development having been extensively identified. It is now widely understood that DNA methylation and histone modification patterns are imprinted during embryonic development and must be maintained in adult cells for appropriate gene transcription and phenotypic stability. A compelling question then is how these epigenetic mechanisms play a role in kidney development. In this review, we describe the major genes and pathways that have been linked to epigenetic mechanisms in kidney development. We also discuss recent applications of single-cell RNA sequencing (scRNA-seq) techniques in the study of kidney development. Additionally, we summarize the techniques of single-cell epigenomics, which can potentially be used to characterize epigenomes at single-cell resolution in embryonic and adult kidneys. The combination of scRNA-seq and single-cell epigenomics will help facilitate the further understanding of early cell lineage specification at the level of epigenetic modifications in embryonic and adult kidney development, which may also be used to investigate epigenetic mechanisms in kidney diseases.


Improving Dissolution Behavior and Oral Absorption of Drugs with pH-Dependent Solubility Using pH Modifiers: A Physiologically Realistic Mass Transport Analysis.
Orally dosed drugs must dissolve in the gastrointestinal (GI) tract before being absorbed through the epithelial cell membrane. In vivo drug dissolution depends on the GI tract's physiological conditions such as pH, residence time, luminal buffers, intestinal motility, and transit and drug properties under fed and fasting conditions (Paixão, P. et al. Mol. Pharm.2018 and Bermejo, et al. M. Mol. Pharm.2018). The dissolution of an ionizable drug may benefit from manipulating in vivo variables such as the environmental pH using pH-modifying agents incorporated into the dosage form. A successful example is the use of such agents for dissolution enhancement of BCS class IIb (high-permeability, low-solubility, and weak base) drugs under high gastric pH due to the disease conditions or by co-administration of acid-reducing agents (i.e., proton pump inhibitors, H2-antagonists, and antacids). This study provides a rational approach for selecting pH modifiers to improve monobasic and dibasic drug compounds' dissolution rate and extent under high-gastric pH dissolution conditions, since the oral absorption of BCS class II drugs can be limited by either the solubility or the dissolution rate depending on the initial dose number. Betaine chloride, fumaric acid, and tartaric acid are examples of promising pH modifiers that can be included in oral dosage forms to enhance the rate and extent of monobasic and dibasic drug formulations. However, selection of a suitable pH modifier is dependent on the drug properties (e.g., solubility and pKa) and its interplay with the pH modifier pKa or pKas. As an example of this complex interaction, for basic drugs with high pKa and intrinsic solubility values and large doses, a polyprotic pH modifier can be expected to outperform a monoacid pH modifier. We have developed a hierarchical mass transport model to predict drug dissolution of formulations under varying pH conditions including high gastric pH. This model considers the effect of physical and chemical properties of the drug and pH modifiers such as pKa, solubility, and particle size distribution. This model also considers the impact of physiological conditions such as stomach emptying rate, stomach acid and buffer secretion, residence time in the GI tract, and aqueous luminal volume on drug dissolution. The predictions from this model are directly applicable to in vitro multi-compartment dissolution vessels and are validated by in vitro experiments in the gastrointestinal simulator. This model's predictions can serve as a potential data source to predict plasma concentrations for formulations containing pH modifiers administered under the high-gastric pH conditions. This analysis provides an improved formulation design procedure using pH modifiers by minimizing the experimental iterations under both in vitro and in vivo conditions.


Satisfactory analgesia with minimal emesis in day surgeries: a randomised controlled trial of morphine versus hydromorphone.
Opioids remain the mainstay therapy for post-surgical pain. Although both morphine and hydromorphone are potent analgesics, it has been suggested that hydromorphone is clinically better. Our primary objective was to compare morphine with hydromorphone for achieving satisfactory analgesia with minimal emesis (SAME). We performed a multicentre RCT in 402 patients having ambulatory surgery. A random computer-generated allocation, stratified by site, was developed by our pharmacy. Concealment was achieved by allocating patients to study groups by nurses using sequentially coded study medication syringes having equi-analgesic doses, made available in the postoperative recovery room. Patients, health providers, and research personnel were blinded. The operating-room protocol allowed for routine anaesthetic management, excluding the use of study medications. Study medications were administered by recovery nurses as per an algorithm. Analyses utilised the intention-to-treat principle, and regression analyses were used for outcomes as appropriate and using multiple imputation. Of 751 patients, 402 were randomised between morphine (n=199) and hydromorphone (n=203). Baseline and intraoperative variables were comparable across the groups. The odds of achieving SAME were similar between the groups (odds ratio: 1.01; 95% confidence interval: 0.57-1.80). There were no differences in the side-effects of severe itching, respiratory depression, or sedation. Patient satisfaction, discharge times, and post-discharge outcomes, including pain and nausea/vomiting over 24 h, were also comparable. There was no difference between morphine and hydromorphone regarding analgesia and common side-effects. The appearance of dose-limiting side-effects is idiosyncratic; the clinical decision must be based on individual responses. NCT02223377.


Radioimmunoreactivity and receptor-binding activity of the recombined molecule obtained by complementation of two fibrinolysin fragments of ovine prolactin.
The recombined molecule obtained by complementation of two fibrinolysin fragments of ovine prolactin (oPRL) has been characterized by radioimmunoassay and radioreceptor assay. The recombinant alone exhibits very low radioimmunoreactivity and radioreceptor activity. However, in the presence of excess fragment oPRL-(1-53), which does not compete with oPRL in either assay, the recombinant has 101% of the radioimmunoreactivity and only 13% of the radioreceptor activity. The result shows that the low activity of the recombinant when assayed alone is due to dissociation of the molecule. When the molecule is completely in the recombined form in the presence of excess oPRL-(1-53), it retains full immunoreactivity but only part of the radioreceptor activity.


Selection on personality in a songbird affects maternal hormone levels tuned to its effect on timing of reproduction.
The increase or decrease in yolk androgens over the laying sequence of a clutch in birds may mitigate or enhance, respectively, the disadvantage of the last-hatched chicks, providing a potentially adaptive tool to adjust brood size to food conditions. This variation may involve a genetic component on which Darwinian selection can act. We found that two lines of a wild bird species selected for bold and shy personalities show, respectively, increased and decreased androgen concentrations over the laying sequence. The line showing the increase laid earlier in the season, when food conditions are normally sufficient to raise the whole brood. The line showing the decrease laid later, when food is normally scarce, which may facilitate brood reduction. The results indicate a correlated response in maternal hormone transfer to genetic selection on personality, which relates to ecological conditions.


Effect of Sexual Function Improvement Program for Breast Cancer Survivors on Sexual Distress, Sexual Satisfaction and Marital Intimacy.
This study was conducted to examine effects of a sexual function improvement program on sexual distress, sexual satisfaction and marital intimacy among breast cancer survivors. With quasi-experimental design, a total of 54 women after breast surgery were assigned into experimental group (n=28) and control group (n=26) after recruited via convenience sampling. They were endocrine surgery outpatients in university hospital at Chonnam province. Experimental group received a sexual function improvement program 5 sessions over 5 weeks. Sexual distress, sexual satisfaction, and marital intimacy were examined with self-report structured questionaries. Data were analyzed using ?2 test, Fisher's exact, independent t-test, and analysis of covariance with SPSS 17.0/window program. Women who participated in the sexual function improvement program had lower sexual distress (F=27.29, p<.001), higher sexual satisfaction (t=3.09, p=.003) higher marital intimacy (F=17.51, p<.001) than the women who did not participate. Results suggest that a sexual function improvement program can be effective strategy to improve sexual distress, sexual satisfaction and marital intimacy. Therefore, this program can be regarded as useful nursing intervention program for breast cancer survivors.


The Tingathe programme: a pilot intervention using community health workers to create a continuum of care in the prevention of mother to child transmission of HIV (PMTCT) cascade of services in Malawi.
Loss to follow-up is a major challenge in the prevention of mother to child transmission of HIV (PMTCT) programme in Malawi with reported loss to follow-up of greater than 70%. Tingathe-PMTCT is a pilot intervention that utilizes dedicated community health workers (CHWs) to create a complete continuum of care within the PMTCT cascade, improving service utilization and retention of mothers and infants. We describe the impact of the intervention on longitudinal care starting with diagnosis of the mother at antenatal care (ANC) through final diagnosis of the infant. PMTCT service utilization, programme retention and outcomes were evaluated for pregnant women living with HIV and their exposed infants enrolled in the Tingathe-PMTCT programme between March 2009 and March 2011. Multivariate logistic regression was done to evaluate maternal factors associated with failure to complete the cascade. Over 24 months, 1688 pregnant women living with HIV were enrolled. Median maternal age was 27 years (IQR, 23.8 to 30.8); 333 (19.7%) were already on ART. Among the remaining women, 1328/1355 (98%) received a CD4 test, with 1243/1328 (93.6%) receiving results. Of the 499 eligible for ART, 363 (72.8%) were successfully initiated. Prior to, delivery there were 93 (5.7%) maternal/foetal deaths, 137 (8.1%) women transferred/moved, 51 (3.0%) were lost and 58 (3.4%) refused ongoing PMTCT services. Of the 1318 live births to date, 1264 (95.9%) of the mothers and 1285 (97.5%) of the infants received ARV prophylaxis; 1064 (80.7%) infants were tested for HIV by PCR and started on cotrimoxazole. Median age at PCR was 1.7 months (IQR, 1.5 to 2.5). Overall transmission at first PCR was 43/1047 (4.1%). Of the 43 infants with positive PCR results, 36 (83.7%) were enrolled in ART clinic and 33 (76.7%) were initiated on ART. Case management and support by dedicated CHWs can create a continuum of longitudinal care in the PMTCT cascade and result in improved outcomes.