Effects of a short-term resistance program using elastic bands versus weight machines for sedentary middle-aged women.
This study was designed to determine whether different effects on functional capacity and body composition were produced by using different devices (elastic bands (EBs) versus weight machines (WMs)) with the same resistance training program. Forty-five healthy sedentary middle-aged women volunteers were chosen and randomly assigned to 1 of 3 groups: 21 subjects trained using EBs (EBG), 14 in trained using WMs (WMG), and 10 were controls (CG). Both exercise groups trained with a periodized muscular endurance program twice a week for 10 weeks, with a total of 6 exercises per session for the major muscle groups. Exercise intensity was equalized by jointly monitoring the same targeted number of repetitions (TNRs) and rate of perceived exertion in active muscles (RPE-AM). Functional capacity was assessed by using knee push-up (KPU) and 60-second squat (S) tests. Body composition was measured using an 8-polar bioelectrical impedance analyzer. The results for both the EBG and WMG show a decrease in fat mass (p = 0.05 and p < 0.01, respectively) and an increase in both the fat-free mass (p < 0.05 and p < 0.01, respectively) and the number of repetitions in the KPU (p < 0.05 and p < 0.01, respectively) and S tests (p < 0.01 in both). None of the variables measured for the CG varied significantly. It can be concluded that, independently of the device used, the combined monitoring of TNRs and RPE-AM can be a valid tool for controlling the resistance exercise intensity and can lead to healthy adaptations. EBs can thus offer significant physiological benefits that are comparable to those obtained from WMs in the early phase of strength training of sedentary middle-aged women.


"Bystander" chest compressions and assisted ventilation independently improve outcome from piglet asphyxial pulseless "cardiac arrest".
Bystander cardiopulmonary resuscitation (CPR) without assisted ventilation may be as effective as CPR with assisted ventilation for ventricular fibrillatory cardiac arrests. However, chest compressions alone or ventilation alone is not effective for complete asphyxial cardiac arrests (loss of aortic pulsations). The objective of this investigation was to determine whether these techniques can independently improve outcome at an earlier stage of the asphyxial process. After induction of anesthesia, 40 piglets (11.5+/-0.3 kg) underwent endotracheal tube clamping (6.8+/-0.3 minutes) until simulated pulselessness, defined as aortic systolic pressure <50 mm Hg. For the 8-minute "bystander CPR" period, animals were randomly assigned to chest compressions and assisted ventilation (CC+V), chest compressions only (CC), assisted ventilation only (V), or no bystander CPR (control group). Return of spontaneous circulation occurred during the first 2 minutes of bystander CPR in 10 of 10 CC+V piglets, 6 of 10 V piglets, 4 of 10 CC piglets, and none of the controls (CC+V or V versus controls, P<0.01; CC+V versus CC and V combined, P=0.01). During the first minute of CPR, arterial and mixed venous blood gases were superior in the 3 experimental groups compared with the controls. Twenty-four-hour survival was similarly superior in the 3 experimental groups compared with the controls (8 of 10, 6 of 10, 5 of 10, and 0 of 10, P<0.05 each). Bystander CPR with CC+V improves outcome in the early stages of apparent pulseless asphyxial cardiac arrest. In addition, this study establishes that bystander CPR with CC or V can independently improve outcome.


Reproductive biology and susceptibility of Florida Culex coronator to infection with West Nile virus.
Abstract Ornithophilic Culex species are considered the primary amplification vectors of West Nile virus (WNV) in bird hosts as well as vectors responsible for epidemic transmission. Culex coronator was first collected from Okaloosa, Santa Rosa, Walton, and Washington Counties in Florida in 2005 and has since spread throughout the state. The vector competence of Cx. coronator for WNV, known to be infected in nature, has not been assessed. Without this knowledge, we are unable to assess this species' potential as an enzootic and epidemic vector of WNV in Florida. In the current study, we investigate the reproductive biology and susceptibility to WNV infection, dissemination, and transmission by Cx. coronator. We show that Cx. coronator is capable of delaying oviposition for several weeks after blood feeding and that the number of eggs laid is greater for avian than mammalian hosts. Cx. coronator were highly susceptible to infection (∼80-100%) and dissemination (∼65-85% by 18 days since exposure) with lower rates of transmission (0-17% at 25°C and 28-67% at 28°C), suggesting that it is a competent vector of WNV under some conditions. The proportion of mosquitoes with disseminated infections related to the time since exposure and was higher at 28°C than at 25°C. The rapid and statewide distribution of Cx. coronator throughout Florida poses as a potential public health risk. This baseline knowledge is essential information for mosquito control and public health agencies to assess current and future disease risk to Southeastern United States.


INFLUENCE OF THE PATIENT'S SEX AND AGE, VOLUMES OF THE SALIVARY GLAND AND PLEOMORPHIC ADENOMA ON THE TUMOR HISTOLOGICAL VARIANTS.
Aim: The purpose of the study was to identify the influence of the patient's sex and age, the volumes of the salivary gland and pleomorphic adenoma on the histological variants of the tumor. Materials and Methods: The study included 21 women and 9 men with pleomorphic adenomas of the salivary gland. In 15 cases, a mesenchymal variant of pleomorphic adenoma was identified, in 5 cases - an epithelial variant, in 10 cases - a mixed variant. The average age of the patients was 39.7±2.9 years. Patients with pleomorphic adenomas underwent magnetic resonance imaging using a Siemens MAGNETOM Aera 1.5T device (Germany), during which three projections of the tumor and salivary gland were measured (antero-posterior, lateral, vertical) with subsequent calculation of their volumes, and then the ratios of these volumes. Classification trees were used to determine whether patients belonged to one of three variants of pleomorphic adenoma. The CART (Classification And Regression Tree) algorithm was used as a branching option. Stopping branching was carried out using the FACT (Fact-style direct stopping) method until each terminal (final) node of the tree does not contain incorrectly classified observations or when their number becomes less than a given proportion of the total group size (less than 5%). Determination of the structure and relationships between the tumor variants and such indicators as gender, age and radiological indicators (volume of the tumor, volume of the salivary gland, ratio of tumor volume to salivary gland volume) was carried out using correspondence analysis. Results: Epithelial variant of pleomorphic adenoma is more typical for women, and the mixed and mesenchymal variant is more common for patients of both sexes. The epithelial variant can develop in patients of any age, while the mixed variant occurs mainly in patients older than 41 years, and the mesenchymal variant - mainly in patients younger than 41 years. The ratio of the volume of the tumor to the volume of the salivary gland will be predominantly >0.17 in the epithelial variant of pleomorphic adenoma, predominantly ≤0.17 in the mesenchymal variant, and can take any value in the mixed variant. Conclusions: The authors conducted a study in order to identify the influence of sex, age of the patient, and the ratio of the volume of pleomorphic adenoma to the volume of the salivary gland on the histological variant of the tumor. The revealed data will be useful in the treatment and diagnostic process in patients with pleomorphic adenoma of the salivary gland.


Nursing research: staying focused. Interview by Cheryl Slagle King.
APNQ interviews Peter I. Buerhaus, PhD, FAAN, Director, Harvard Nursing Research Institute, Assistant Professor, Department of Health Policy and Management at the Harvard School of Public Health, who advocates APNs involvement in validating their contribution to improving the health of the communities they serve; further education of employers and managed care organizations regarding the utility of APNs; evaluating the quality of these educational programs and the application of their practice; focusing research resources to gain maximum benefit for the nursing profession and patient populations.


The Lived Experiences of Bereaved Filipino Families of the Deceased Due to the COVID-19 Pandemic.
The typical highlight of Filipino mourning of conducting funerals and burials has ceased due to recent health guidelines which required the deceased, who tested positive for the virus, to be cremated and buried right away to avoid further spread of the disease - making bereavement more complicated. This paper investigates the experiences of bereaved Filipino families who lost their loved ones to COVID-19 through a qualitative research design. Researchers explored the experiences of at least three (3) COVID-19 bereaved families through a descriptive phenomenological approach and analyzed the data using thematic analysis to extract the bereavement process experienced by the participants. The findings of the study highlight the changes to the Filipino funeral practice caused by the pandemic and the major roles of connectedness, and cultural and religious beliefs in the Filipino bereavement experience.


Technical note: A novel approach to estimate dry matter intake of lactating dairy cows through multiple on-cow accelerometers.
The objective of this study was to evaluate the feasibility of using multiple 3-dimensional accelerometers to estimated individual dry matter intake (DMI) of lactating dairy cows. Twenty-four Holstein cows in late lactation were assigned into 2 groups, a calibration group (n = 12) and a validation group (n = 12). All cows were fitted with 3 sensors that recorded 3-dimensional acceleration (i.e., x, y, and z) at 10-s intervals, 1 on the lateral side of the left hind leg and 2 attached directly to a halter over the nose and jaw area on the left side. Then, 3 accelerations were generated from each accelerometer (e.g., Leg-X, Leg-Y, and Leg-Z). Six new variables were created based on the change in acceleration in the nose and jaw accelerometers between 2 consecutive time points (e.g., LagJaw-X). For both groups (i.e., calibration and validation), cows were continuously video recorded while data on acceleration and intake of total mixed ration were collected for 10 consecutive days. Cows were fed once daily using an individual gate system, and individual refusals were recorded next day before morning feeding. Cows were fed a common lactating cow diet (17.9% crude protein; 1.70 Mcal/kg of dry matter). In the calibration group, individual eating bouts were obtained based on video recordings and merged with the corresponding accelerometer data. Then, a stepwise regression analysis was conducted using the REG procedure of SAS (SAS Institute, Cary, NC) to determine the ranges in acceleration that accounted for the highest variation in DMI (highest R2) in each acceleration variable. All 32,767 potential acceleration combinations were tested in the validation group using the acceleration ranges predetermined in the calibration group. The CORR procedure of SAS was used to test the Pearson correlation coefficient (r) between the type of DMI [i.e., based on accelerations (DMIaccel) or actual DMI (DMIactual)]. The MIXED procedure of SAS was used to perform a repeated-measures analysis with type (DMIaccel vs. DMIactual), day, and their interaction (T × D) in the model. From this analysis, 8 candidate acceleration models were selected based on high r and similarity (P > 0.15) in terms of T and T × D between DMIaccel and DMIactual. A simulated effect on DMIactual was artificially created in the validation group by dividing this group (n = 12) into high and low intake cows (n = 6/group; DMI of 24.1 vs. 18.7 kg/d), and the candidate models were tested to determine whether they were sensitive enough to detect this effect. From these candidate models, AEN (Leg-X + Jaw-Z + LagJaw-Z) showed a weak correlation (r = 0.36) between DMIaccel and DMIactual, but DMIaccel and DMIactual were highly similar (21.2 vs. 21.4 kg/d of DMI). In addition, this was the only model that could detect the simulated effect on DMIactual (22.1 vs. 20.3 kg/d of DMI) in the validation group. The fact that the simulated effect on DMIactual was detected based only on accelerations is highly significant, and models such as AEN could be substantially improved if they were derived from a greater sample size and included different physiological stages in dairy cows.


[Catecholamine levels in plasma and cerebrospinal fluid of neurosurgical patients with normal and elevated intracranial pressure].
Catecholamine levels in the plasma and cerebrospinal fluid of 21 neurosurgical patients with hydrocephalus and with normal and elevated intracranial pressure were determined prospectively in a clinical study. The study comprised 11 patients with normal intracranial pressure (8 female, 3 male, group 1) and 10 patients with elevated intracranial pressure (6 female, 4 male, group 2). The patients underwent a ventriculo-peritoneal shunt operation, external ventricular drainage or ventriculocisternostomy. The measuring times were set as follows: time 1: pre-operative; time 2: intra-operative; time 3: post-operative. The anaesthetic for the operations was administered as a total intravenous anaesthesia with propofol and alfentanil, muscle relaxation being achieved with rocuronium bromide or cis-atracurium. Measurements of the catecholamine levels (adrenaline, noradrenaline and dopamine) at the three set times revealed an intra-operative fall compared to the initial pre-operative value and a rise in the catecholamine level again after the operation. It is likely that this largely reflects the course of the anaesthetic. The fall in the plasma catecholamine level was much slighter in group with elevated intracranial pressure. But in the group of patients with elevated intracranial pressure the catecholamine levels found in the plasma were much higher than those of the patients without elevated pressure. In the case of adrenaline, it was possible to demonstrate a statistically significant difference at the three measuring times. This suggests that especially the analyzed adrenaline level in the plasma could take on the role of a marker in cases of elevated intracranial pressure. In group 2, with elevated intracranial pressure, the catecholamine levels in the cerebrospinal fluid (CSF) were considerably higher than those in group 1, but the difference did not reach the significance level. The lack of correlation between the catecholamine values in the plasma and CSF described in the literature (comparison of the corresponding values at time 2) was confirmed for noradrenaline and dopamine in patients with elevated intracranial pressure (group 2). In both groups of patients there was a CSF plasma gradient for dopamine at time 2, i. e. the dopamine level was higher in cerebrospinal fluid than in the plasma. The study shows that even a slight rise in intracranial pressure without clinically detectable ischaemia may result in elevated plasma and CSF catecholamine levels. Although catecholamine values are not routine parameters, they can be used in developing procedures to protect the brain in neurosurgical patients.


Totally Laparoscopic Resection for Low Sigmoid and Rectal Cancer Using Natural Orifice Specimen Extraction Techniques.
A minilaparotomy for specimen extraction during laparoscopy occasionally results in postoperative wound complications. We have performed a totally laparoscopic resection for early colorectal cancer using the natural orifice specimen extraction technique. From 2008 to 2013, we have performed a totally laparoscopic resection for clinical stage I and IIA low sigmoid colon and rectal cancers. A prospectively maintained database was reviewed to assess the outcomes after surgery. In total, 40 patients had high anterior resections using transanal specimen extraction, and 32 patients had low anterior resections with transanal pull-through. Eight patients (11%) reported conversion to conventional laparoscopic colorectal resections; anastomotic leakages occurred in 4 patients (5.6%). No mortality or cancer recurrence was observed during 42.5±16.2 months of follow-up. One natural orifice specimen extraction technique, known as transanal specimen extraction, has emerged as a promising form of totally laparoscopic surgical intervention for early-stage cancers of the low sigmoid colon and rectum.


Hip osteotomy arthroplasty: ten-year follow-up.
We previously reported the initial success of combined osteotomy and arthroplasty of the hip for arthritis with femoral deformity. This technique has gained acceptance. We now report, for the first time, the ten year clinical and radiographic results with histology of 2 specimen. The osteotomies healed and the proximal femoral segment remained viable. One of three patients is symptom free without subsequent operative treatment. One of three patients had revision for acetabular loosening at eight years and biopsy of the proximal femur showed the proximal femoral segment to be viable. One of three patients had loosening of a macrofit bipolar prosthesis which required revision to total hip replacement at five years. Histology revealed viability of the proximal femur. All three patients are doing well at ten year follow-up. Based on the results of this study and current knowledge, the technique of osteotomy and arthroplasty for hip arthritis associated with femoral deformity is effective when combined with current techniques of ingrowth femoral component of total hip arthroplasty.


How to Internationalize Medical Education using Concepts in Internationalization of Higher Education.
This article was migrated. The article was marked as recommended. Internationalization of higher education is a well-researched area with a long history. At a time of increasing globalization, particularly in light of recent global health events, the internationalization of medical education may play an important role in medical school teaching - increasing future medical collaboration and building a global medical community. Internationalization of medical education is a less researched discipline and often limited to areas of Global Health. It is typically not part of the standard medical curriculum. While internationalization of medical education has overlapping themes with Global Health education, it has a much wider scope (i.e., preparation of global citizen physicians, international employability, collaboration, cultural and international understanding). Lessons learned from concepts in internationalization of higher education can aid in the realization of internationalization of medical education programs and establish IoME as a distinct area of educational research. This paper suggests elements to consider when implementing programs in internationalization of medical education. Guided by the analysis of an existing program in internationalization of medical education, important components are highlighted from the perspective of concepts found in internationalization of higher education. Several elements that are important features in internationalization of higher education are emphasized - institutional partnerships, goal setting, variety of internationalization at home concepts, international classroom features, multi-directional student mobility, and sustainability. The authors aim to shed light on the area of internationalization of medical education, widen its scope from Global Health education, and introduce it as a field of study for educational research. Adapting models and concepts of international higher education can help with establishing this field.


Expression, purification and characterization of the suppressor of copper sensitivity (Scs) B membrane protein from Proteus mirabilis.
Suppressor of copper sensitivity (Scs) proteins play a role in the bacterial response to copper stress in many Gram-negative bacteria, including in the human pathogen Proteus mirabilis. Recently, the ScsC protein from P. mirabilis (PmScsC) was characterized as a trimeric protein with isomerase activity that contributes to the ability of the bacterium to swarm in the presence of copper. The CXXC motif catalytic cysteines of PmScsC are maintained in their active reduced state by the action of its membrane-bound partner protein, the Proteus mirabilis ScsB (PmScsB). Thus, PmScsC and PmScsB form a redox relay in vivo. The predicted domain arrangement of PmScsB comprises a central transmembrane β-domain and two soluble, periplasmic domains, the N-terminal α-domain and C-terminal γ-domain. Here, we provide a procedure for the recombinant expression and purification of the full-length PmScsB protein. Using Lemo21 (DE3) cells we expressed PmScsB and, after extraction and purification, we were able to achieve a yield of 3 mg of purified protein per 8 L of bacterial culture. Furthermore, using two orthogonal methods - AMS labelling of free thiols and a scrambled RNase A activity assay - PmScsB is shown to catalyze the reduction of PmScsC. Our results demonstrate that the PmScsC and PmScsB redox relay can be reconstituted in vitro using recombinant full-length PmScsB membrane protein. This finding provides a promising starting point for the in vitro biochemical and structural characterization of the P. mirabilis ScsC and ScsB interaction.


Towards a framework for treatment effectiveness in schizophrenia.
Prompt administration of antipsychotic treatment that is adhered to is essential for the optimal treatment of schizophrenia. Many patients have benefited from the advent of second-generation antipsychotics, which can offer good symptomatic control with reduced incidence of extrapyramidal symptoms, although with higher risk of metabolic side effects. It is unsurprising that accounts as to whether first- and second-generation antipsychotics differ in their efficacy vary, since treatment effectiveness is a broad notion and difficult to define. Numerous factors may be used to gauge treatment effectiveness and, while it has largely been defined in terms of improvements in four domains (symptoms of disease, treatment burden, disease burden, and health and wellness), the real-world clinical utility of this consensus is unclear. Therefore, this article aims to provide a framework that can aid psychiatrists in making assessments about treatment effectiveness. A panel of 12 psychiatrists and psychopharmacologists convened to develop and propose an accessible and globally-applicable framework for assessing the effectiveness of antipsychotic treatments in patients with schizophrenia. Following presentation of a preliminary proposal to a wider group of psychiatrists from across Europe, it was refined into a framework comprising five domains: symptomatic remission and retention of treatment; affective symptoms; cognitive functioning; treatment satisfaction; and personal and social functioning - each of which is discussed in this article. This article provides a framework that can aid psychiatrists in making assessments about treatment effectiveness. It is anticipated that the framework outlined here may contribute to improving clinical practice through the promotion of a patient-centered approach to the assessment of treatment effectiveness, using five specified domains, in patients with schizophrenia.


Temporal expression, polar distribution and transition of an epitope domain in the perinuclear theca during mouse spermatogenesis.
A novel domain of epitopes is expressed by a family of high-Mr proteins at the anterior pole of the germ cell nucleus during spermiogenesis, and later by two low-Mr proteins at the anterior and posterior poles of the nucleus during sperm maturation in the epididymis. Initially, monoclonal antibodies (mAbs) PNT-1 (IgG2b) and PNT-2 (IgG2a) bound to antigens present in a cap-like configuration at the apical pole of the spermatid nucleus at step 5 of spermiogenesis. The distribution of epitopes on the nucleus expanded posteriorly until, in testicular sperm they covered the anterior pole down to the distal limits of the subacrosomal perforatorium. By contrast, sperm from the epididymis and vas deferens bound both mAbs in two distinct regions on the nucleus, one on the dorsal margin of the anterior pole, and the other in a ventral zone at the posterior pole. On SDS-PAGE and isoelectric focusing (IEF) immunoblots, both mAbs bound three major proteins with Mr of approximately 80,000, 77,000 and 75,000 from spermatids and testicular sperm, and proteins of Mr 50,000 and 48,000 in epididymal and vas deferens sperm. Both the high- and low-Mr protein families were recovered in germ cell nuclear/perinuclear matrices. Their mobilities on SDS-PAGE were not altered by exo- or endoglycosidases or by aminoethylation in denaturing conditions. mAb PNT-1 bound to the sperm proteins with a Ka of 3.53 x 10(12) M-1 and mAb PNT-2 with a Ka of 2.08 x 10(12) M-1. From competition binding data, mAbs PNT-1 to -10 appeared to recognize six adjacent or overlapping epitopes on the same proteins. These data suggest the high-Mr proteins, the thecins, present at the anterior pole of haploid germ cells are processed at the onset of sperm maturation to yield two low-Mr proteins that then occupy two distinct domains at the anterior and posterior poles of the nucleus.


Effect of scleral shortening on axial length.
Partial thickness sclerectomy is the most commonly employed scleral shortening technique used in conjunction with pars plana vitrectomy in the repair of myopia-associated macular holes in patients with staphyloma. Recently, scleral shortening induced through scleral invagination has been advocated as an adjunct in retinal translocation surgery. To determine whether a correlation exists between the amount of sclera infolding and the posttreatment reduction in axial length (AL) as a result of lamellar scleral resectioning or full-thickness scleral invagination. Three groups of 10 eyes each underwent lamellar scleral resection with dissection of 6, 8, and 10 mm in height, and 1 group of 10 eyes underwent a 10-mm invagination. Presurgical and postsurgical external AL of globes with stabilized intraocular pressure was measured to +/-0.022-mm precision. Average (+/-SD) AL shortening following lamellar resections for 6-, 8-, and 10-mm groups were 1.50+/-0.24, 2.10+/-0.13, and 2.65+/-0.24 mm, respectively, and 2.50+/-0.23 mm for the 10-mm invagination group. Differences in AL before and after scleral shortening were found to be significantly different between dissections of different heights (P<.05), and not significantly different between the 10-mm resection and invagination groups (P>.17). The AL of each group was shortened by approximately 25% of the resection-invagination height. The relation was quasilinear. Lamellar scleral resection and nonresected scleral invagination reduce the ocular AL. The extent of the reduction significantly correlates to the amount of removed or invaginated sclera. Surgical shortening of the sclera is useful in the management of several retinal disorders, but causes significant changes in AL. Arch Ophthalmol. 2000;118:965-968


[Pain and cognition].
Pain is a multidimensional subjective experience mediated by emotion, attitudes and other perceptual influences. The functional deficit of patients suffering from pain could be expressed by a cognitive complaint. In this paper, cognitive repercussions of pain, associated factors and iatrogenic factors are presented. According to all the relation between pain and cognition seems complex and involves factors such as depression, anxiety, and medical treatment among others. All these factors interact together and produce a specific cognitive complaint for each patient.


Lignin modification leads to increased nodule numbers in alfalfa.
Reduction of lignin levels in the forage legume alfalfa (Medicago sativa) by down-regulation of the monolignol biosynthetic enzyme hydroxycinnamoyl coenzyme A:shikimate hydroxycinnamoyl transferase (HCT) results in strongly increased digestibility and processing ability of lignocellulose. However, these modifications are often also associated with dwarfing and other changes in plant growth. Given the importance of nitrogen fixation for legume growth, we evaluated the impact of constitutively targeted lignin modification on the belowground organs (roots and nodules) of alfalfa plants. HCT down-regulated alfalfa plants exhibit a striking reduction in root growth accompanied by an unexpected increase in nodule numbers when grown in the greenhouse or in the field. This phenotype is associated with increased levels of gibberellins and certain flavonoid compounds in roots. Although HCT down-regulation reduced biomass yields in both the greenhouse and field experiments, the impact on the allocation of nitrogen to shoots or roots was minimal. It is unlikely, therefore, that the altered growth phenotype of reduced-lignin alfalfa is a direct result of changes in nodulation or nitrogen fixation efficiency. Furthermore, HCT down-regulation has no measurable effect on carbon allocation to roots in either greenhouse or 3-year field trials.


Predictors of recurrence after radiotherapy for non-melanoma skin cancer.
Predictive factors of recurrence were examined in 448 non-melanoma skin cancers (72% basal cell carcinoma, 28% squamous cell carcinoma) treated with radiotherapy. The overall recurrence rate was 15.8% at a median follow-up of 18.4 months. In multivariate analysis, significant factors for recurrence were age (p = 0.0197), tumour size 2 cm or greater (p = 0.0095), immunosuppression (p = 0.0082), and treatment modality (p = 0.0009).


Noradrenaline and functional plasticity in kitten visual cortex: a re-examination.
A quantitative re-examination was made of the influence of noradrenergic depletion on the epigenesis of kitten visual cortex. Two methods were used to deplete noradrenaline at the cortical level: stereotaxically controlled injection of 6-hydroxydopamine (6-OHDA) in the coeruleus complex, from which the noradrenergic input to visual cortex arises; intraventricular injection of 6-OHDA. The latter chemical lesion also depleted dopamine levels in the brain. Lesion of the noradrenergic or catecholaminergic systems was performed neonatally or at an age of 3-4 weeks in kittens submitted to five different rearing procedures: normal rearing, dark rearing, monocular rearing, monocular exposure following dark rearing and monocular deprivation following normal rearing. Forty-two kittens between 3 and 12 weeks of age were used for this biochemical and electrophysiological study. Noradrenaline and dopamine levels were measured by a radioenzymatic method in the primary visual cortex of twenty-six kittens. A total of 1263 cells were recorded in area 17 of twenty-six kittens. Combined biochemical and electrophysiological data were obtained in ten 6-OHDA-lesioned kittens. Whatever the mode of chemical lesion used, cortical noradrenergic depletion failed to block either maturation or vision-dependent processes which are known to affect orientation selectivity and/or ocular dominance during the critical period. However, in some cases, the amplitude of the epigenetic functional modifications was slightly reduced in 6-OHDA-treated kittens. The cortical effects of monocular deprivation starting from the age of 5 weeks were studied quantitatively both in lesioned and intact kittens. Disappearance of noradrenaline in area 17 did not prevent the loss of binocularity in cortical cells. However, even when monocular occlusion had been maintained for 2 or 3 weeks in 6-OHDA-treated kittens, ocular dominance shifts were limited to a stage equivalent to that observed in the intact kitten after 5-8 days of monocular occlusion. The amplitude of this partial protective effect was found to be unrelated either to the delay following the chemical lesion, or to the level of noradrenaline remaining in lesioned kitten cortex. Although a putative gating role of noradrenaline cannot be excluded in the development of the intact animal, this report shows that its presence is not required for functional plasticity to occur in kitten area 17.


Burden and Characteristics of Unsolicited Emails from Medical/Scientific Journals, Conferences, and Webinars to Faculty and Trainees at an Academic Pathology Department.
Professionals and trainees in the medical and scientific fields may receive high e-mail volumes for conferences and journals. In this report, we analyze the amount and characteristics of unsolicited e-mails for journals, conferences, and webinars received by faculty and trainees in a pathology department at an academic medical center. With informed consent, we analyzed 7 consecutive days of e-mails from faculty and trainees who voluntarily participated in the study and saved unsolicited e-mails from their institutional e-mail address (including junk e-mail folder) for medical/scientific journals, conferences, and webinars. All e-mails were examined for characteristics such as reply receipts, domain name, and spam likelihood. Journal e-mails were specifically analyzed for claims in the message body (for example, peer review, indexing in databases/resources, rapid publication) and actual inclusion in recognized journal databases/resources. A total of 17 faculty (4 assistant, 4 associate, and 9 full professors) and 9 trainees (5 medical students, 2 pathology residents, and 2 pathology fellows) completed the study. A total of 755 e-mails met study criteria (417 e-mails from 328 unique journals, 244 for conferences, and 94 for webinars). Overall, 44.4% of e-mails were flagged as potential spam by the institutional default settings, and 13.8% requested reply receipts. The highest burden of e-mails in 7 days was by associate and full professors (maximum 158 or approximately 8200 per year), although some trainees and assistant professors had over 30 e-mails in 7 days (approximately 1560 per year). Common characteristics of journal e-mails were mention of "peer review" in the message body and low rates of inclusion in recognized journal databases/resources, with 76.4% not found in any of 9 journal databases/resources. The location for conferences in e-mails included 31 different countries, with the most common being the United States (33.2%), Italy (9.8%), China (4.9%), United Kingdom (4.9%), and Canada (4.5%). The present study in an academic pathology department shows a high burden of unsolicited e-mails for medical/scientific journals, conferences, and webinars, especially to associate and full professors. We also demonstrate that some pathology trainees and junior faculty are receiving an estimated 1500 unsolicited e-mails per year.


[Immunostimulating action of polysaccharides (heteroglycans) from higher plants].
From the water or alcaline-water extracts of Echinacea purpurea (L.) Moench. and -angustifolia DC., Eupatorium cannabium L. and -perfoliatum L., Chamomilla recutita L. Rauscher, Calendula officinalis L., Baptisia tinctoria (L.) R. B., Achyrocline satureioides DC., Arnica montana L., Sabal serrulata Roem. et Schult., and Eleutherococcus (Acanthopanax) senticosus Maxim. polysaccharide fractions with molecular weights in the range of 25 000 to 500 000 and higher have been isolated, which, according to the granulocytes- and carbon clearance tests, showed significant immunostimulating activities. The isolated compounds belong to the group of watersoluble, acidic branched-chain heteroglycans. Their immunostimulating activity is compared and discussed with respect to other polysaccharides of biological activity.


Computer-Aided, Resistance Gene-Guided Genome Mining for Proteasome and HMG-CoA Reductase Inhibitors.
Secondary metabolites (SMs) are biologically active small molecules, many of which are medically valuable. Fungal genomes contain vast numbers of SM biosynthetic gene clusters (BGCs) with unknown products, suggesting that huge numbers of valuable SMs remain to be discovered. It is challenging, however, to identify SM BGCs, among the millions present in fungi, that produce useful compounds. One solution is resistance gene-guided genome mining, which takes advantage of the fact that some BGCs contain a gene encoding a resistant version of the protein targeted by the compound produced by the BGC. The bioinformatic signature of such BGCs is that they contain an allele of an essential gene with no SM biosynthetic function, and there is a second allele elsewhere in the genome. We have developed a computer-assisted approach to resistance gene-guided genome mining that allows users to query large databases for BGCs that putatively make compounds that have targets of therapeutic interest. Working with the MycoCosm genome database, we have applied this approach to look for SM BGCs that target the proteasome β6 subunit, the target of the proteasome inhibitor fellutamide B, or HMG-CoA reductase, the target of cholesterol reducing therapeutics such as lovastatin. Our approach proved effective, finding known fellutamide and lovastatin BGCs as well as fellutamide- and lovastatin-related BGCs with variations in the SM genes that suggest they may produce structural variants of fellutamides and lovastatin. Gratifyingly, we also found BGCs that are not closely related to lovastatin BGCs but putatively produce novel HMG-CoA reductase inhibitors.


[Energy losses from a short bowel: not only fat].
Two adult patients, men aged 43 and 45 years, with Crohn's disease, complicated by high-output small-bowel-stomy and short-bowel syndrome due to several intestinal resections, presented with extreme weight loss. Although both patients followed a high-calorie diet combining solid foods and enteral nutrition by nasogastric tube, containing 16,000 kJ and 21,000 kJ, respectively, weight loss continued. Faecal fat excretion and basal metabolic rate were determined, but these could not explain the caloric deficit. Therefore, faecal bomb calorimetry, a measurement of total faecal energy content, was also performed, revealing a considerably higher faecal energy loss than had been calculated from faecal fat excretion; this indicates that faecal carbohydrate loss plays an important supplementary role. A stable weightwas achieved in both patients by prescribing extra food. Therefore, faecal fat excretion is an insufficient indicator of total faecal calorie loss in patients with high-output stomata and short-bowel syndrome. Bomb calorimetry may be considered as a tool to determine the remaining absorptive capacity in short-bowel patients.


Immediate Effect of Dry Needling at Myofascial Trigger Point on Hand Spasticity in Chronic Post-stroke Patients: A Multicenter Randomized Controlled Trial.
Background: Hand spasticity after stroke influences the rehabilitation of hand function. Immediate and effective relief of spasticity potentially creates conditions for later rehabilitation training, which has far-reaching significance in the smooth transition of patients to the recovery period. Objective: To evaluate the immediate effect of dry needling (DN) at myofascial trigger point on hand spasticity in stroke patients. Methods: This was a prospective, evaluator blind, multicenter, randomized controlled study. A total of 210 participants were randomly divided into DN group (DN, N = 70), sham dry needling group (SDN, N = 70), and control group (N = 70). Participants in the DN group were treated with DN at myofascial trigger point five times (30 min each time) every week for 4 weeks. Subjects in the SDN group were manipulated the same way as in the DN group, except that the acupuncture site was located in the area adjacent to the myofascial trigger point, which constituted a SDN. Routine rehabilitation treatment was performed for participants in the two groups and in the control group. The primary evaluation index was the immediate effect of hand spasticity relief. Secondary evaluation indicators included the cumulative effect of hand spasticity relief from baseline to week 4, and the changes in flexion angles of the wrist, thumb, and fingers 2-5 in the rest position before, immediately after, and 4 weeks after intervention. Results: The immediate effective rate of spasticity relief (thumb, fingers 2-5, and wrist) of patients with different degrees of spasticity in the DN group was higher than that in the control and SDN groups (thumb, χ2 = 55.833, P < 0.001; fingers 2-5, χ2 = 68.096, P < 0.001; wrist, χ2 = 49.180, P < 0.001) (P < 0.05). The effective rate of spasticity relief from baseline to 4 weeks in the DN group exceeded that in the control group and SDN groups (thumb, χ2 = 8.806, P = 0.012; fingers 2-5, χ2 = 8.087, P = 0.018; and wrist, χ2 = 8.653, P = 0.013) (P < 0.05). No difference in immediate and cumulative effect was found between the control group and SDN group. The change of joints flexion angles in resting position before and after each treatment in the DN group was higher than that in the control and SDN groups (P < 0.05), but it was not significantly different between the control group and SDN group. At 4 weeks, although the change in the DN group was higher than that in the control group and SDN group, this difference was not statistically significant (P > 0.05). Conclusion: Dry needling can relieve varying degrees of hand spasticity instantly in post-stroke. Trial Registration: www.chictr.org.cn, ChiCTR1900022379.


Familial hyperamylasemia.
A 7-year-old white boy was referred to us with a history of 3 attacks of hypogastric pain over the previous 2 years and persistently elevated serum amylase concentrations. At physical examination, he was well with no evidence of clinical abnormalities. His weight and height were normal. Laboratory diagnostic investigations were all normal except for the presence of Ascaris lumbricoides in the feces and persistently elevated serum amylase levels. Serum amylase determinations in the family members were normal in his father and maternal grandmother but elevated in his mother, sister, maternal aunt, and uncle, all of whom asymptomatic. Macroamylasemia was excluded in the child and in the mother. The finding of persistently elevated amylasemia in the child and in the other family members spanning 3 generations, and the exclusion of diseases that lead to hyperamilasemia are consistent with the diagnosis of familial hyperamylasemia. Until now, only 1 similar case has been reported. Familial hyperamylasemia must be considered in the differential diagnosis of hyperamylasemias in childhood.


Long-term metformin use may improve clinical outcomes in diabetic patients with non-alcoholic steatohepatitis and bridging fibrosis or compensated cirrhosis.
Metformin may protect against hepatocellular carcinoma and mortality among patients with type 2 diabetes. To investigate whether long-term use of metformin improves survival and reduces liver-related outcomes among patients with type 2 diabetes and non-alcoholic steatohepatitis. A total of 191 diabetic patients with biopsy-proven non-alcoholic steatohepatitis and bridging fibrosis or compensated cirrhosis were retrospectively identified at Indiana University Medical Center between October 2004 and January 2016. Of them, 110 were users and 81 never-users of metformin. Primary outcomes were transplant-free survival, development of hepatocellular carcinoma or a first event of hepatic decompensation. Cirrhosis was present in 85% of metformin users and 88% of nonusers. Metformin dose was greater than or equal to 1 g/d in 104 out of 110 users and its median duration of use was 6 (95% CI: 4.4-7.9) years. The mean follow-up was 6.92 and 6.80 years for metformin users and non-users, respectively. During follow-up, 28 patients developed hepatocellular carcinoma (metformin users: 7, nonusers: 21), and 52 died (metformin users: 7, nonusers: 24) or were transplanted (metformin users: 13, non-users: 13). Metformin use was associated with lower risk of overall mortality or transplant (HR: 0.42; 95% CI: 0.24-0.74, P = 0.003) and hepatocellular carcinoma (sHR: 0.25; 95% CI: 0.11-0.58, P = 0.001), and remained independently associated with both outcomes after propensity-score and covariate-adjusted analyses. No instances of hepatotoxicity or lactic acidosis were observed. Our study demonstrated an association between long-term metformin use and reduced the risk of all-cause mortality/transplant and hepatocellular carcinoma in diabetics with non-alcoholic steatohepatitis and advanced fibrosis.


Techniques in the prevention and management of seromas after breast surgery.
Seromas are the most frequent complications following breast surgery, resulting in significant discomfort and morbidity with possible delays in commencing adjuvant therapies. Varied clinical practices exist in the techniques employed to prevent and manage seromata. This article assesses published literature on the techniques employed in prevention of seroma formation following breast surgery, evaluating the different methodologies used. Although prevention is the best strategy, seromata remain problematic and we consider their management. The principle findings were that prevention is key to the management of seromata. Methods employed to prevent seromata include suction drainage, shoulder immobilization, quilting sutures, fibrin sealants and innovative measures of managing the axilla, among others. The evidence demonstrated that a combination of quilting and drains significantly reduces the incidence and volumes of seromata. These effects are sustained by minimizing use of electrocautery, alongside increasing frequencies of axillary sentinel lymph node biopsies and node sampling. The efficacy data on fibrin sealants is inconclusive and consequently should not be routinely used alone or accompanied by quilting sutures. Clinically significant seromas deemed 'symptomatic' by patients and complicating infected seromas should be aspirated. There are limited data on the recommended treatment of established seromas with a paucity of high-quality studies and further research involving randomized trials are indicated.


Single and Multiple Gate Design Optimization Algorithm for Improving the Effectiveness of Fiber Reinforcement in the Thermoplastic Injection Molding Process.
Fiber reinforcement orientation in thermoplastic injection-molded components is both a strength as well as a weak point of this largely employed manufacturing process. Optimizing the fiber orientation distribution (FOD) considering the shape of the part and the applied loading conditions allows for enhancing the mechanical performances of the produced parts. Henceforth, this research proposes an algorithm to identify the best injection gate (IG) location/s starting from a 3D model and a user-defined load case. The procedure is composed of a first Visual Basic Architecture (VBA) code that automatically sets and runs Finite Volume Method (FVM) simulations to find the correlation between the fiber orientation tensor (FOT) and the IG locations considering single and multiple gates combinations up to three points. A second VBA code elaborates the results and builds a dataset considering the user-defined loading and constraint conditions, allowing the assignment of a score to each IG solution. Three geometrical components of increasing complexity were considered for a total of 1080 FVM simulations and a total computational time of ~390 h. The search for the best IG location has been further expanded by training a Machine Learning (ML) model based on the Gradient Boosting (GB) algorithm. The training database (DB) is based on FVM simulations and was expanded until a satisfactory prediction accuracy higher than 90% was achieved. The enhancement of the local FOD on the critical regions of three components was verified and showed an average improvement of 26.9% in the stiffness granted by a high directionality of the fibers along the load path. Finite element method (FEM) simulations and laboratory experiments on an industrial pump housing, injection-molded with a polyamide-66 reinforced with 30% of short glass fibers (PA66-30GF) material were also carried out to validate the FVM-FEM simulation frame and showed a 16.4% local stiffness improvement in comparison to the currently employed IG solution.


Outpatient neurosurgery in neuro-oncology.
Technological breakthroughs along with modern application of awake craniotomy and new neuroanesthesia protocols have led to a progressive development in outpatient brain tumor surgery and improved surgical outcomes. As a result, outpatient neurosurgery has become a standard of care at the authors' center due to its clinical benefits and impact on patient recovery and overall satisfaction. On the other hand, the financial savings derived from its application is also another favorable factor exerting influence on patients, health care systems, and society. Although validated several years ago and with recent data supporting its application, outpatient brain tumor surgery has not gained the traction that it deserves, based on scientific skepticism and perceived potential for medicolegal issues. The goal of this review, based on the available literature and the senior author's experience in outpatient brain tumor surgery, was to evaluate the most important aspects regarding indications, clinical outcomes, economic burden, and patient perceptions.


Race and diabetic nephropathy.
Blacks who are at a greater risk of renal failure than whites also experience a greater prevalence of diabetic nephropathy. Preliminary data suggest that black uremic diabetics fare less well than whites following a kidney transplant. Planning treatment for the diabetic with progressive renal insufficiency requires an allowance for the high probability that coincident multisystem disease will develop. We now understand that the mysterious concept of unmanageable "brittle diabetes" was a myth derived from flawed interaction between patient and physician. By establishing a team approach, the patient is protected from the stress of having conflicting treatment protocols prescribed by physicians concerned with only one organ or system. Black diabetics who may often have less family income than whites may require more intensive support from social workers and diabetes educators to understand and cope with the burden of kidney failure. The majority of uremic diabetics, both black and white, can survive at least the first 3 years of dialysis or renal transplantation with preserved sight and intact limbs. It may be anticipated that the proportion of nephropathic diabetics who attain rehabilitation will continue to increase.


Automated non-alphanumeric symbol resolution in clinical texts.
Although clinical texts contain many symbols, relatively little attention has been given to symbol resolution by medical natural language processing (NLP) researchers. Interpreting the meaning of symbols may be viewed as a special case of Word Sense Disambiguation (WSD). One thousand instances of four common non-alphanumeric symbols ('+', '-', '/', and '#') were randomly extracted from a clinical document repository and annotated by experts. The symbols and their surrounding context, in addition to bag-of-Words (BoW), and heuristic rules were evaluated as features for the following classifiers: Naïve Bayes, Support Vector Machine, and Decision Tree, using 10-fold cross-validation. Accuracies for '+', '-', '/', and '#' were 80.11%, 80.22%, 90.44%, and 95.00% respectively, with Naïve Bayes. While symbol context contributed the most, BoW was also helpful for disambiguation of some symbols. Symbol disambiguation with supervised techniques can be implemented with reasonable accuracy as a module for medical NLP systems.


Palbociclib in hormone receptor positive advanced breast cancer: A cost-utility analysis.
The addition of palbociclib to letrozole improves progression-free survival in the first-line treatment of hormone receptor positive advanced breast cancer (ABC). This study assesses the cost-utility of palbociclib from the Canadian healthcare payer perspective. A probabilistic discrete event simulation (DES) model was developed and parameterised with data from the PALOMA 1 and 2 trials and other sources. The incremental cost per quality-adjusted life-month (QALM) gained for palbociclib was calculated. A time horizon of 15 years was used in the base case with costs and effectiveness discounted at 5% annually. Time-to- progression and time-to-death were derived from a Weibull and exponential distribution. Expected costs were based on Ontario fees and other sources. Probabilistic sensitivity analyses were conducted to account for parameter uncertainty. Compared to letrozole, the addition of palbociclib provided an additional 14.7 QALM at an incremental cost of $161,508. The resulting incremental cost-effectiveness ratio was $10,999/QALM gained. Assuming a willingness-to-pay (WTP) of $4167/QALM, the probability of palbociclib to be cost-effective was 0%. Cost-effectiveness acceptability curves derived from a probabilistic sensitivity analysis showed that at a WTP of $11,000/QALM gained, the probability of palbociclib to be cost-effective was 50%. The addition of palbociclib to letrozole is unlikely to be cost-effective for the treatment of ABC from a Canadian healthcare perspective with its current price. While ABC patients derive a meaningful clinical benefit from palbociclib, considerations should be given to increase the WTP threshold and reduce the drug pricing, to render this strategy more affordable.


STUDY OF BULL SPERMATOZOA. QUANTITATIVE ELECTRON MICROSCOPY.
The electron microscope has been used to determine the characteristic dimensions and the distribution of the dry mass in bull spermatozoa. The most important result is that all characteristic data are occurring in logarithmic distributions. Furthermore, no correlation between such parameters as head weight and tail weight or head length and tail length was found. The occurrence in logarithmic distributions and the non-correlation of parts in the assembly of a spermatozoon are considered to reflect significant biologic principles. Methodologically, a new procedure is added to quantitative electron microscopy permitting the recording of the mass cross-section (total mass per unit length) of an object. This approach makes possible determinations of the distribution and the total mass of very long and narrow structures.


Asymmetric cell divisions in the epidermis.
Generation of three-dimensional tissues with distinct cell types is required for the development of all organs. On its own, mitotic spindle orientation allows tissues to change in length or shape. In combination with intrinsic or extrinsic cues, this can also be coupled to the generation of diverse cell fates-a process known as asymmetric cell division (ACD). Understanding ACDs has been greatly aided by studies in invertebrate model systems, where genetics and live imaging have provided the basis for much of what we know. ACDs also drive the development and differentiation of the epidermis in mammals. While similar to the invertebrate models, the epidermis is distinct in balancing symmetric and asymmetric divisions to yield a tissue of the correct surface area and thickness. Here, we review the roles of spindle orientation in driving both morphogenesis and cell fate decisions. We highlight the epidermis as a unique model system to study not only basic mechanisms of ACD but also their regulation during development.


Mechanisms of Colorectal Cancer Prevention by Aspirin-A Literature Review and Perspective on the Role of COX-Dependent and -Independent Pathways.
Aspirin, synthesized and marketed in 1897 by Bayer, is one of the most widely used drugs in the world. It has a well-recognized role in decreasing inflammation, pain and fever, and in the prevention of thrombotic cardiovascular diseases. Its anti-inflammatory and cardio-protective actions have been well studied and occur through inhibition of cyclooxygenases (COX). Interestingly, a vast amount of epidemiological, preclinical and clinical studies have revealed aspirin as a promising chemopreventive agent, particularly against colorectal cancers (CRC); however, the primary mechanism by which it decreases the occurrences of CRC has still not been established. Numerous mechanisms have been proposed for aspirin's chemopreventive properties among which the inhibition of COX enzymes has been widely discussed. Despite the wide attention COX-inhibition has received as the most probable mechanism of cancer prevention by aspirin, it is clear that aspirin targets many other proteins and pathways, suggesting that these extra-COX targets may also be equally important in preventing CRC. In this review, we discuss the COX-dependent and -independent pathways described in literature for aspirin's anti-cancer effects and highlight the strengths and limitations of the proposed mechanisms. Additionally, we emphasize the potential role of the metabolites of aspirin and salicylic acid (generated in the gut through microbial biotransformation) in contributing to aspirin's chemopreventive actions. We suggest that the preferential chemopreventive effect of aspirin against CRC may be related to direct exposure of aspirin/salicylic acid or its metabolites to the colorectal tissues. Future investigations should shed light on the role of aspirin, its metabolites and the role of the gut microbiota in cancer prevention against CRC.


Longitudinal evaluation of expression of virally delivered transgenes in gerbil cone photoreceptors.
Delivery of foreign opsin genes to cone photoreceptors using recombinant adeno-associated virus (rAAV) is a potential tool for studying the basic mechanisms underlying cone based vision and for treating vision disorders. We used an in vivo retinal imaging system to monitor, over time, expression of virally-delivered genes targeted to cone photoreceptors in the Mongolian gerbil (Meriones unguiculatus). Gerbils have a well-developed photopic visual system, with 11-14% of their photoreceptors being cones. We used replication deficient serotype 5 rAAV to deliver a gene for green fluorescent protein (GFP). In an effort to direct expression of the gene specifically to either S or M cones, the transgene was under the control of either the human X-chromosome opsin gene regulatory elements, i.e., an enhancer termed the locus control region (LCR) and L promoter, or the human S-opsin promoter. Longitudinal fluorescence images reveal that gene expression is first detectable about 14 days post-injection, reaches a peak after about 3 months, and is observed more than a year post-injection if the initial viral concentration is sufficiently high. The regulatory elements are able to direct expression to a subpopulation of cones while excluding expression in rods and non-photoreceptor retinal cells. When the same viral constructs are used to deliver a human long-wavelength opsin gene to gerbil cones, stimulation of the introduced human photopigment with long-wavelength light produces robust cone responses.


gamma-Sodium gallate: a Rietveld refinement using X-ray powder diffraction.
Tetrahedrally coordinated oxides usually present polymorphism, but for NaGaO(2), only the beta polymorph has been reported. In this work, the synthesis and structural characterization of gamma-sodium gallate, gamma-NaGaO(2), are presented. The crystal structure belongs to the orthorhombic system, space group Pbca (No. 61), and has been characterized by a Rietveld refinement of the X-ray powder diffraction pattern. The structure is similar to those exhibited by the gamma phases of many tetrahedral oxides.


Peri-ocular proliferative apocrine hidrocystoma (cystadenoma): A clinicopathological case series.
Apocrine cystadenomas are rare, benign tumors that might arise in the periocular region from glands of Moll. They characteristically demonstrate proliferative features on histopathological examination, which differentiate them from simple hidrocystomas. We retrospectively identified 4 consecutive cases of apocrine cystadenomas in male patients with a mean age of 48.5 years (range 20-62). One of the cases was a recurrent lesion. The Preoperative clinical diagnosis was mostly hidrocystoma. All patients agreed on complete surgical excision of their cystic lesions. Histopathological review of the excised cysts confirmed the diagnosis of apocrine cystadenoma based on the presence of proliferative features with no atypia or infiltrative behavior. Cases are summarized in Table 1 and the histopathological appearance is demonstrated in the included figure. Apocrine cystadenoma is rare. It occurs in the areas of skin with hair follicles, such as the axilla, neck, and trunk, and may be mistaken for other skin lesions, such as nevi or syringomas. In the eyelid region, they are commonly missed and frequently diagnosed as simple hidrocystoma due to the presence of bluish hue such as in our series. Recurrence is rare but was found in one of our patients at initial presentation. Our series included unique locations of this lesion in the medial canthus in one patient and near the eyelid tarsus in another. Ophthalmologist should be aware of the rare occurrence of this lesion in the periocular region. Further studies to explain the etiology of such proliferative nature in apocrine cysts would be interesting.


Role of scavenger receptor a family in lung inflammation from exposure to environmental particles.
Both immune and non-immune cells express an extensive array of scavenger receptors that bind a variety of ligands including bacterial cell-wall components and lipoproteins. Over the past several years, significant advances have been made in elucidating the role of scavenger receptors, predominantly Class A scavenger receptors SR-A I/II and MARCO, on macrophages in the binding of environmental particles such as crystalline silica and titanium dioxide. Recent evidence indicates that the binding of crystalline silica to scavenger receptors leads to apoptosis of macrophages and release of mediators (e.g., proinflammatory cytokines) contributing to lung inflammation and fibrosis. In this review, we examine the evidence for the role of SR-A I/II and MARCO in binding of the environmental particles and signaling initiated by particle-receptor interaction. Emerging concepts on the molecular details of signaling cascades by engagement of scavenger receptors by the environmental particles are also discussed.


Stimulation of proinsulin biosynthesis and insulin release by pyruvate and lactate.
Increasing concentrations of pyruvate failed to stimulate proinsulin biosynthesis and insulin release in freshly isolated islets. Glycolytic flux (3H2O from [5-3H]glucose) decreased by 80-85%, but decarboxylation of [1(-14)C]pyruvate was unaffected in islets tested immediately after alloxan exposure. This strongly suggested that in freshly isolated islets, beta-cells, in relation to other islet cells, hardly contribute to the decarboxylation of pyruvate. Non-alloxan-treated cultured islets decarboxylated 2-2.5 times as much pyruvate as did alloxan-treated islets cultured for 15-18h. Thus the contribution of beta-cells to the metabolism of pyruvate after culturing markedly increased. Concomitantly beta-cells became responsive to pyruvate. At 20mM-pyruvate, release of prelabelled proinsulin and insulin and incorporation of [3H]leucine into proinsulin reached values approximately half of those obtained with 20mM-glucose. Lactate was as effective as pyruvate in inducing responses in cultured islets. The experiments indicate that a critical degree of substrate utilization is necessary for the generation of signals for insulin release and proinsulin biosynthesis.


Whole-wheat flour particle size influences dough properties, bread structure and in vitro starch digestibility.
Whole-wheat flour (WWF) is increasingly popular because of the health benefits of whole grains. This study investigated the effect of WWF particle size on dough properties, bread quality and in vitro starch digestibility. WWF was made from intact whole grain directly. Three WWF particle sizes were examined, including coarse, medium and fine with a mean size of 1315, 450 and 199 μm, respectively. The dough made from WWF of a larger particle size exhibited lower extensibility and stability, and subsequently the bread had a more compact structure (i.e. lower open porosity and thicker cell thickness), smaller specific volume and harder texture, which were regarded as poor quality attributes. On the other hand, the bread made from the fine WWF exhibited a higher amount of released glucose than those made from the coarse and medium WWFs. Moreover, the particle size of bread bolus showed no significant effect on in vitro starch digestion. The whole study demonstrated that the particle size of WWF plays a critical role in determining both bread quality and digestibility.


High-throughput screening of compounds targeting RNA editing in Trypanosoma brucei: Novel molecular scaffolds with broad trypanocidal effects.
Mitochondrial uridine insertion/deletion RNA editing, catalyzed by a multiprotein complex (editosome), is essential for gene expression in trypanosomes and Leishmania parasites. As this process is absent in the human host, a drug targeting this mechanism promises high selectivity and reduced toxicity. Here, we successfully miniaturized our FRET-based full-round RNA editing assay, which replicates the complete RNA editing process, adapting it into a 1536-well format. Leveraging this assay, we screened over 100,000 compounds against purified editosomes derived from Trypanosoma brucei, identifying seven confirmed primary hits. We sourced and evaluated various analogs to enhance the inhibitory and parasiticidal effects of these primary hits. In combination with secondary assays, our compounds marked inhibition of essential catalytic activities, including the RNA editing ligase and interactions of editosome proteins. Although the primary hits did not exhibit any growth inhibitory effect on parasites, we describe eight analog compounds capable of effectively killing T. brucei and/or Leishmania donovani parasites within a low micromolar concentration. Whether parasite killing is - at least in part - due to inhibition of RNA editing in vivo remains to be assessed. Our findings introduce novel molecular scaffolds with the potential for broad antitrypanosomal effects.


Socio-Demographic Characteristics of COVID-19 Vaccine Recipients in Kwara State, North Central Nigeria.
Understanding key socio-demographic variables of 2019 coronavirus disease (COVID-19) vaccine recipients is crucial to improving its acceptance and Nigeria's COVID-19 control strategy. The survey was conducted as a non-probability cross-sectional survey of 2,936 COVID-19 vaccine recipients in Kwara State. Our findings revealed that 74% (n = 2,161) of the vaccine recipients were older than 40 years. Forty percent (n = 1,180) of the vaccine recipients earned a monthly income >100,000 Naira (equivalent to US $200). Most of the vaccine recipients (64%, n = 1,880) had tertiary education, while 15% (n = 440) of them had no formal education. Almost half of the recipients (47%, n = 1,262) were government employees and 28.8% (n = 846) of them had health-related backgrounds. Only 17% (n = 499) of the vaccine recipients have been screened for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), of which 21% (n = 105/499) of them were tested positive. Only 47% (n = 1,378) had been fully immunized. The prevalence of confirmed COVID-19 cases among COVID-19 vaccine recipients in Kwara State was 3.6% (n = 105/2,936). The most recurrent adverse events following immunization (AEFIs) among vaccine recipients were fever (14%, n = 411), pain at injection site (47%, n = 1,409), headache (19%, n = 558), and body weakness (9%, n = 264). The need to protect themselves from the deadly virus was the main reason that prompted people to voluntarily accept the COVID-19 vaccine. There is a high level of COVID-19 vaccine acceptance among respondents across all social classes including those with no formal education, those with very low monthly income (< US $2 per day), and in untested population. Hence, vaccine donors should prioritize equitable distribution to Low-and-Middle-income Countries (LMICs) such as Nigeria, and health authorities should improve vaccine advocacy to focus on vaccine safety and efficacy.


A clinical calculator to predict disease outcomes in women with triple-negative breast cancer.
Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, characterized by substantial risks of early disease recurrence and mortality. We constructed and validated clinical calculators for predicting recurrence-free survival (RFS) and overall survival (OS) for TNBC. Data from 605 women with centrally confirmed TNBC who underwent primary breast cancer surgery at Mayo Clinic during 1985-2012 were used to train risk models. Variables included age, menopausal status, tumor size, nodal status, Nottingham grade, surgery type, adjuvant radiation therapy, adjuvant chemotherapy, Ki67, stromal tumor-infiltrating lymphocytes (sTIL) score, and neutrophil-to-lymphocyte ratio (NLR). Final models were internally validated for calibration and discrimination using ten-fold cross-validation and compared with their base-model counterparts which include only tumor size and nodal status. Independent external validation was performed using data from 478 patients diagnosed with stage II/III invasive TNBC during 1986-1992 in the British Columbia Breast Cancer Outcomes Unit database. Final RFS and OS models were well calibrated and associated with C-indices of 0.72 and 0.73, as compared with 0.64 and 0.62 of the base models (p < 0.001). In external validation, the discriminant ability of the final models was comparable to the base models (C-index: 0.59-0.61). The RFS model demonstrated greater accuracy than the base model both overall and within patient subgroups, but the advantages of the OS model were less profound. This TNBC clinical calculator can be used to predict patient outcomes and may aid physician's communication with TNBC patients regarding their long-term disease outlook and planning treatment strategies.


[Current concept of schizophrenia: state of the art].
Approaches to diagnosing schizophrenia are different. There is a distinct tendency either to narrow the limits of the disease or to expand it, which in some cases leads to a disagreement and even a tendency to disputes. The comprehensive studies conducted in the Mental Health Research Center, Russian Academy of Medical Sciences, have provided an overall notion of the disease in terms of its progression and outcome. The clinical picture of schizophrenia is characterized by obligatory specific disorders, such as autism, reduced energy potential, emotional thinking, and behavioral disorders. Personality changes may be seen as the smoothening of specific personality traits and the appearance of the features that are not inherent to the patients in the past. Schizophernia is also characterized by positive psychopathological syndromes: pseudoneurotic, affective, psychopathy-like, hallucinatory-paranoid and catatonic. A study of 7500 patients with schizophrenia demonstrated that there were clear-cut regularities in the development of the disease, which suggest that there are forms and types in its progression. The study identified 3 forms of development: continuous, recurrent, and attack-like progressive with varying degrees and rates of the process (severe, moderate, and mild). Genealogical and clinicogenetic studies demonstrated accumulation of psychoses and abnormal personalities in the families of probands, manifest and slowly progressive forms of schizophrenia and cases of schizoid psychopathy. Among the wide spectrum of pathogenetic concepts, priority should be given to the dopamine hypothesis, whose main point is accumulation of an excessive amount of dopamine in the brain tissue, especially in the nigrostriatal, mesocortical, and mesolimbic systems. This may lead to activation of dopaminergic brain structures with an increase of dopamine receptors. This hypothesis is confirmed by the neuropathological studies demonstrating a significant increase in the numerical density of the dendritic spines and dendritic trunks in the with layer of the prefrontal cortex. The highest index of the numerical density was observed in young patients with prevalent negative disorders. Inasmuch as there is no correlation of this index with the duration of the disease, it can be concluded that the abundance of synaptical connections is a result of disturbed brain development and a factor predisposing to severe progression of schizophrenia. Treatment modalities are determined by the form and rate of progression of and the pattern of the psychopathological syndrome. Of particular importance is the role of age, somatic state, and individual sensitivity to neuroleptic drugs. Another important factor in the treatment of schizophrenia is a simultaneous or consecutive impact on the psychopathological syndrome and the disease as a whole.


Connecting salt stress signalling pathways with salinity-induced changes in mitochondrial metabolic processes in C3 plants.
Salinity exerts a severe detrimental effect on crop yields globally. Growth of plants in saline soils results in physiological stress, which disrupts the essential biochemical processes of respiration, photosynthesis, and transpiration. Understanding the molecular responses of plants exposed to salinity stress can inform future strategies to reduce agricultural losses due to salinity; however, it is imperative that signalling and functional response processes are connected to tailor these strategies. Previous research has revealed the important role that plant mitochondria play in the salinity response of plants. Review of this literature shows that 2 biochemical processes required for respiratory function are affected under salinity stress: the tricarboxylic acid cycle and the transport of metabolites across the inner mitochondrial membrane. However, the mechanisms by which components of these processes are affected or react to salinity stress are still far from understood. Here, we examine recent findings on the signal transduction pathways that lead to adaptive responses of plants to salinity and discuss how they can be involved in and be affected by modulation of the machinery of energy metabolism with attention to the role of the tricarboxylic acid cycle enzymes and mitochondrial membrane transporters in this process.


Circulating aldosterone induces the apical accumulation of the proton pumping V-ATPase and increases proton secretion in clear cells in the caput epididymis.
Clear cells express the vacuolar proton-pumping H(+)-ATPase (V-ATPase) and acidify the lumen of the epididymis, a process that is essential for male fertility. The renin-angiotensin-aldosterone system (RAAS) regulates fluid and electrolyte balance in the epididymis, and a previous study showed binding of aldosterone exclusively to epididymal clear cells (Hinton BT, Keefer DA. Steroid Biochem 23: 231-233, 1985). We examined here the role of aldosterone in the regulation of V-ATPase in the epididymis. RT-PCR showed expression of the mineralocorticoid receptor [MR; nuclear receptor subfamily 3, group C member 2 (NR3C2)] and 11-β-dehydrogenase isozyme 2 (HSD11β2) mRNAs specifically in clear cells, isolated by fluorescence-activated cell sorting from B1-enhanced green fluorescent protein (EGFP) mice. Tail vein injection of adult rats with aldosterone, 1,2-dioctanoyl-sn-glycerol (DOG), or 8-(4-chlorophenylthio)-cAMP (cpt-cAMP) induced V-ATPase apical membrane accumulation and extension of V-ATPase-labeled microvilli in clear cells in the caput epididymis but not in the cauda. V-ATPase activity was measured in EGFP-expressing clear cells using the intracellular pH (pHi)-sensing dye seminaphthorhodafluor-5F-5-(and 6)-carboxylic acid, acetoxymethyl ester acetate (SNARF-5F). Aldosterone induced a rapid increase in the rate of Na(+)- and bicarbonate-independent pHi recovery following an NH4Cl-induced acid load in clear cells isolated from the caput but not the cauda. This effect was abolished by concanamycin A, spironolactone, and chelerythrine but not myristoylated-protein kinase inhibitor (mPKI) or mifepristone. Thus aldosterone increases V-ATPase-dependent proton secretion in clear cells in the caput epididymis via MR/NR3C2 and PKC activation. This study, therefore, identifies aldosterone as an active member of the RAAS for the regulation of luminal acidification in the proximal epididymis.


Reference intervals for radiographic, echocardiographic and N-terminal pro B-type natriuretic peptide values in healthy kittens.
Assessment of heart size in kittens is important, and there is a need for reference intervals (RIs) to prevent misinterpretation of cardiomegaly in this patient population. The purpose of this study was to generate RIs for echocardiographic and radiographic quantification of cardiac size in healthy kittens. In total, 88 kittens aged 6-16 weeks were enrolled in this study. Physical examination, and radiographic and echocardiographic evaluations were performed without sedation. Thoracic radiographs and echocardiographic images were measured to establish RIs for vertebral heart score (VHS), cardiac thoracic ratio (CTR) and multiple echocardiographic variables. N-terminal pro B-type natriuretic peptide (NT-proBNP) was measured. Statistical correlations between echocardiographic parameters and age, body weight and sex were all evaluated and RIs were generated. Low-grade heart murmurs were appreciated in 26/88 kittens (29.5%). Kittens had a median VHS of 9.5 vertebrae (95% RI 8.0-10.9) and a median CTR of 67.2% (95% RI 54.4-79.8%). Measured NT-proBNP levels were comparable to healthy adult cats with a median of 31 pmol/l (upper reference limit 75 pmol/l). Multiple moderate-to-strong correlations between body weight and age with various echocardiographic parameters were observed and allometric scaling was performed for body weight. RIs for echocardiographic parameters were generated based on patient weight using allometric scaling formulas. Tricuspid valve regurgitation was a common finding and was present in 37.5% (n = 33) of the kittens. This study establishes RIs for thoracic radiograph assessment, echocardiography and cardiac biomarkers in kittens, which fills a critical gap in the veterinary literature. The VHS reported in this study is higher than previously reported for adult cats.


Reciprocal upregulation of scavenger receptors complicates interpretation of nanoparticle uptake in non-phagocytic cells.
Nanoparticles have great potential as drug delivery vehicles or as imaging agents for treatment and diagnosis of various diseases. It is therefore crucial to understand how nanoparticles are taken up by cells, both phagocytic and non-phagocytic. Small interference RNA has previously been used to isolate the effect of particular receptors in nanoparticle uptake by silencing their expression. Here we show that, when it comes to receptors with overlapping function, interpretation of such data has to be done with caution. We followed the uptake of silica nanoparticles by scavenger receptors in A549 lung epithelial cells. While we successfully knocked-down gene expression of several different receptors within the scavenger receptor family (SR-A1, MARCO, SR-BI, LOX-1 and LDLR) this caused reciprocal up and down regulation of the other scavenger receptors. Subsequent nanoparticle uptake experiments in silenced cells exhibit a complex behaviour, which could easily be misinterpreted if reciprocal regulation is not considered. Preliminary identification of the actual scavenger receptors involved can be found by disentangling the effects mathematically. Finally, we show that the effects are still present under more realistic biological conditions, namely at higher serum concentrations.


Clinical interventions that increase the uptake and success of vaginal birth after caesarean section: a systematic review.
The aim of this study was to review clinical interventions that increase the uptake and/or the success rates of vaginal birth after caesarean section. Repeat caesarean section is the main reason for the increase in surgical births. The risk of uterine rupture in women who have prior caesarean sections prevents many clinicians from recommending vaginal birth after caesarean. Despite this, support for vaginal birth after caesarean continues. A search of five databases and a number of relevant professional websites was undertaken up to December 2008. A systematic review of quantitative studies that involved a comparison group and examined a clinical intervention for increasing the uptake and/or the success of vaginal birth after caesarean section was undertaken. An assessment of quality was made using the Critical Skills Appraisal Programme. Induction of labour using artificial rupture of membranes, prostaglandins, oxytocin infusion or a combination, was associated with lower vaginal birth rates. Cervical ripening agents such as prostaglandins and transcervical catheters may result in lower vaginal birth rates compared with spontaneous labour. The impact of epidural anaesthesia in labour on vaginal birth after caesarean success is inconclusive. X-ray pelvimetry is associated with reduced uptake of vaginal birth after caesarean and higher caesarean section rates. Scoring systems to predict likelihood of vaginal birth are largely unhelpful. There is insufficient data in relation to vaginal birth after caesarean section between different closure methods for the primary caesarean section. Clinical factors can affect vaginal birth after caesarean uptake and success.


Cloning and heterologous expression of cellulose free thermostable xylanase from Bacillus brevis.
Xylanase gene isolated from Bacillus brevis was expressed in E. coli BL21. Sequencing of the gene (Gen Bank accession number: HQ179986) showed that it belongs to family 11 xylanases. The recombinant xylanase was predominantly secreted to culture medium and showed mesophilic nature (optimum activity at 55°C and pH 7.0). The cell free culture medium exhibited 30 IU/ml xylanse activity. The enzyme did not show any cellulose activity and was active under wide range of temperature (40°C to 80°C) and pH (4 to 9). The enzyme showed considerable thermo stability and regained over 90% of activity, when returned to 55°C after boiling for 5 min. These physiochemical properties of B. brevis xylanse show high potential of its applications in paper and pulp industry.


Functional integrin subunits regulating cell-matrix interactions in the intervertebral disc.
Cellular interactions with the extracellular matrix are key factors regulating cell survival, differentiation, and response to environmental stimuli in cartilagenous tissues. Much is known about the extracellular matrix proteins in the intervertebral disc (IVD) and their variations with region, age, or degenerative state of the tissue. In contrast, little is known of the integrin cell surface receptors that directly bind to and interact with these matrix proteins in the IVD. In almost all tissues, these integrin-mediated cell-matrix interactions are important for transducing environmental cues arising from mechanical stimuli, matrix degradation fragments, and cytokines into intracellular signals. In this study, cells from the nucleus pulposus and anulus fibrosus regions of porcine IVDs were analyzed via flow cytometry to quantify integrin expression levels upon isolation and after monolayer culture. Assays of cell attachment to collagens, fibronectin, and laminin were performed after functional blocking of select integrin subunits to evaluate the role of specific integrins in cell attachment. In situ distribution and co-localization of integrins and laminin were also characterized. Results identify integrin receptors critical for IVD cell interactions with collagens (alpha1beta1) and fibronectin (alpha5beta1). Additionally, dramatic differences in cell-laminin interactions were observed between cells of the nucleus and anulus regions, including differences in alpha6 integrin expression, cell adhesion to laminin, and in situ pericellular environments. These findings suggest laminin-cell interactions may be important and unique to the nucleus pulposus region of the IVD. The results of this study provide new information on functional cell-matrix interactions in tissues of the IVD.


Anaemia in pregnancy among Aboriginal and Torres Strait Islander women of Far North Queensland: A retrospective cohort study.
Anaemia during pregnancy is common worldwide. In Australia between 7.1% and 11% of mothers have been reported to have anaemia in pregnancy. Higher rates are reported for Aboriginal and Torres Strait Islander women (Townsville: 34.2%, remote Northern Territory: 50%). The present study describes anaemia in pregnancy among Aboriginal and Torres Strait Islander women of Far North Queensland. Health service information was analysed for 2076 Aboriginal and Torres Strait Islander women who gave birth between 2006 and 2010. The prevalence of anaemia in pregnancy, characteristics of the mothers and pregnancy outcomes were described. Logistic regression for bivariate analyses and multivariable linear modelling with and without imputed data were used to compare those mothers who had anaemia in pregnancy with those who did not. More than half of Aboriginal and Torres Strait Islander women (54.5% (95% CI: 52.4%, 56.7%)) had anaemia in pregnancy. For mothers who gave birth in 2009 and 2010 (n = 1796) with more complete data, those who were iron deficient during pregnancy were more likely to be anaemic (RR: 1.40, P = <0.001). Mothers (29.0%) from localities of relative socioeconomic advantage had lower risk of anaemia in pregnancy (RR: 0.86, P = 0.003), as did mothers (31.9%) who were obese (RR: 0.87, P = 0.013). The prevalence of anaemia in pregnancy among Aboriginal and Torres Strait Islander women of Far North Queensland is high. Prevention and treatment of anaemia will improve the health of these mothers, and possibly the health and early development of their children.


Total hip replacement in patients with Parkinson's disease.
From 1970 to 1994, 107 total hip arthroplasties (THAs) were performed in 98 patients with Parkinson's disease. The average age of the patients was 72 years. Preoperative diagnoses were osteoarthrosis in 58 hips, failed endoprosthesis in 19, aseptic loosening in ten, femoral neck fracture in 18, and other diagnoses in two. Milder neurological stages I-III were assigned to 96 patients, and tendon release for contracture was performed in eight patients. Of the 38 complications eight were urinary tract infections and six dislocations. Of these 15 occurred in the 58 primary THAs and 23 in the 49 nonprimary THAs. In patients with primary THAs there were no dislocations; however, one of the four postoperative deaths occurred following primary THA. We followed 75 hips for 7 (2-21) years; 51 patients had died by the time of the study. Neurological status deteriorated over time with 57% of patients progressing to functional stages IV or V, although consistent improvement was noted for pain relief. Function was directly related to the stage of the neurological disease.


Early experience alters brain function and structure.
To investigate the effects of early experience on brain function and structure. A randomized clinical trial tested the neurodevelopmental effectiveness of the Newborn Individualized Developmental Care and Assessment Program (NIDCAP). Thirty preterm infants, 28 to 33 weeks' gestational age (GA) at birth and free of known developmental risk factors, participated in the trial. NIDCAP was initiated within 72 hours of intensive care unit admission and continued to the age of 2 weeks, corrected for prematurity. Control (14) and experimental (16) infants were assessed at 2 weeks' and 9 months' corrected age on health status, growth, and neurobehavior, and at 2 weeks' corrected age additionally on electroencephalogram spectral coherence, magnetic resonance diffusion tensor imaging, and measurements of transverse relaxation time. The groups were medically and demographically comparable before as well as after the treatment. However, the experimental group showed significantly better neurobehavioral functioning, increased coherence between frontal and a broad spectrum of mainly occipital brain regions, and higher relative anisotropy in left internal capsule, with a trend for right internal capsule and frontal white matter. Transverse relaxation time showed no difference. Behavioral function was improved also at 9 months' corrected age. The relationship among the 3 neurodevelopmental domains was significant. The results indicated consistently better function and more mature fiber structure for experimental infants compared with their controls. This is the first in vivo evidence of enhanced brain function and structure due to the NIDCAP. The study demonstrates that quality of experience before term may influence brain development significantly.


Detection of multiple hepatitis C virus genotypes in a cohort of injecting drug users.
Multiple genotypes of the hepatitis C virus (HCV) were detected in five of 138 HCV RNA positive injecting drug users (IDUs) recruited in Melbourne, Australia. Two were detected by combined LiPA and core and NS5a region sequencing, and three more (selected for testing due to their high-risk behaviour) by heteroduplex mobility analysis. We conclude that the true prevalence of mixed infection in IDUs is undoubtedly higher than the 3.6% (five of 138) we observed, and is underestimated by LiPA, the most common method of genotyping. As responsiveness to HCV treatment varies significantly with genotype, a high prevalence of mixed HCV infections in IDUs must diminish overall treatment efficacy and lessen our ability to reduce the burden of HCV-related disease.


The metabolism of hyaluronan in cultured rabbit growth plate chondrocytes during differentiation.
Hyaluronan (HA) is one of the major extracellular matrix components in cartilage. In addition to the biomechanical functions, HA has various important roles in the differentiation of chondrocytes. The purpose of this study was to clarify the nature of HA synthesis during chondrocyte differentiation. Growth plate chondrocytes were isolated from rabbit ribs and cultured in chondrocyte differentiation medium. The amount of HA and HA synthase (HAS) mRNA levels were analyzed for each stage of chondrocyte differentiation by means of high-performance liquid chromatography (HPLC) and real-time PCR, respectively. The distribution of HA in cultured chondrocytes was observed by histochemical staining. The amount of HA, ranging widely in size, was increased substantially during the hypertrophic stage. The expression levels of HAS2 and HAS3 mRNAs were low during the matrix-forming stage. HAS2 mRNA level was substantially enhanced at the pre-hypertrophic stage, whereas HAS3 mRNA level exhibited a slight increase. HAS1 mRNA was not detected. The intensity of HA staining was high around the hypertrophic chondrocytes. These results suggest that HA metabolism in chondrocyte differentiation is regulated by the selective expression of HASs, and HAS2 and the related large size-HA may have a certain association with the hypertrophic changes of chondrocytes.


Association of Opioids With Incisional Ocular Surgery.
Opioid abuse has been declared a public health emergency. Currently, little is known about the association between opioids and ocular surgery. To characterize rates of filled opioid prescriptions after incisional ocular surgeries. This cohort study included patients with incisional ocular surgeries within a large national US insurer's administrative medical claims database. All incisional ocular surgeries from January 2000 through December 2016 were evaluated. An opioid prescription was eligible if it occurred from 1 day before to 7 days after a surgery. Any surgery on a patient who was younger than 18 years, had more than 30 consecutive days of an opioid prescription in the prior 6 months, or had less than 6 months of data in the database prior to surgery was excluded. Data analysis occurred from May 2018 through November 2018. The rate of opioid prescriptions filled for all incisional ocular surgeries from 2000 through 2016. Primary analysis looked at the rate of filled opioid prescriptions for each ophthalmic subspecialty surgery over time. Secondary analysis assessed which patient or surgical characteristics (ie, age, sex, race/ethnicity, geographic locations, yearly income, educational level, and type of eye surgery) were associated with filling an opioid prescription. Multivariate logistic regression using generalized estimating equations was used to determine odds ratios (ORs) of filling an opioid prescription. A total of 2 407 962 incisional ocular surgeries were included, of which 45 776 (1.90%) were associated with an opioid prescription. The rate of filled opioid prescriptions varied considerably over time, with the lowest rate occurring in the 2000-2001 cohort year (671 of 45 776 [1.24%]) and the highest in 2014 (5559 of 45 776 [2.51%]). An increasing trend was seen over the course of the study (2000-2001: 671 of 45 776 [1.24%]; 2016: 5851 of 45 776 [2.07%]; P < .001). Multivariate logistic regression showed that year of surgery was significantly associated with filling an opioid prescription, with the highest odds in 2014 (OR, 3.71 [95% CI, 3.33-4.1]), 2015 (OR, 3.33 [95% CI, 2.99-3.70]), and 2016 (OR, 3.27 [95% CI, 2.94-3.63]) compared with 2000 to 2001 (P < .001). These findings suggest the rate of filled opioid prescriptions are increasing for all types of incisional ocular surgery over time. Given the ongoing national opioid epidemic, understanding patterns of use can help in reversing the epidemic.


A FRET-based ratiometric fluorescent and colorimetric probe for the facile detection of organophosphonate nerve agent mimic DCP.
A FRET ratiometric fluorescent probe enabling a fast and highly sensitive response to OP nerve agent mimic DCP within 1 min and with as low as 0.17 ppm concentration detection limit has been developed. Moreover, the probe exhibits noticeable color changes under UV light and even with the naked eye. It is also demonstrated that it can detect both liquid and gas nerve agents.


The importance of providing counselling and financial support to patients receiving treatment for multi-drug resistant TB: mixed method qualitative and pilot intervention studies.
People with multi-drug resistant tuberculosis (MDR-TB) in low-income countries face many problems during treatment, and cure rates are low. The purpose of the study was (a) to identify and document the problems experienced by people receiving care for MDR-TB, and how they cope when support is not provided, to inform development of strategies; (b) to estimate the effectiveness of two resultant strategies, counselling alone, and joint counselling and financial support, of increasing DOTS-plus treatment success under routine programme conditions. A mixed-method study comprising a formative qualitative study, pilot intervention study and explanatory qualitative study to better understand barriers to completion of treatment for MDR-TB. Participants were all people starting MDR-TB treatment in seven DOTS-plus centres in the Kathmandu Valley, Nepal during January to December 2008. The primary outcome measure was cure, as internationally defined. MDR-TB treatment caused extreme social, financial and employment hardship. Most patients had to move house and leave their job, and reported major stigmatisation. They were concerned about the long-term effects of their disease, and feared infecting others. In the resultant pilot intervention study, the two strategies appeared to improve treatment outcomes: cure rates for those receiving counselling, combined support and no support were 85%, 76% and 67% respectively. Compared with no support, the (adjusted) risk ratios of cure for those receiving counselling and receiving combined support were 1.2 (95% CI 1.0 to 1.6) and 1.2 (95% CI 0.9 to 1.6) respectively. The explanatory study demonstrated that patients valued both forms of support. MDR-TB patients are extremely vulnerable to stigma and extreme financial hardship. Provision of counselling and financial support may not only reduce their vulnerability, but also increase cure rates. National Tuberculosis Programmes should consider incorporating financial support and counselling into MDR-TB care: costs are low, and benefits high, especially since costs to society of incomplete treatment and potential for incurable TB are extremely high.


Life history variables preserved in dental cementum microstructure.
The age and season of death of mammals, as well as other aspects of their life history, can be estimated from seasonal bands in dental cementum that result from variations in microstructure. Scanning electron micrographs of goats fed controlled diets demonstrate that cementum bands preserve variations in the relative orientation of collagen fibers that reflect changes in the magnitude and frequency of occlusal forces from chewing different quality diets. Changes in the rate of tissue growth are also reflected in cementum bands as variations in the degree of mineralization.