Confidentiality, privacy, and security of genetic and genomic test information in electronic health records: points to consider.
As clinical genetics evolves, and we embark down the path toward more personalized and effective health care, the amount, detail, and complexity of genetic/genomic test information within the electronic health record will increase. This information should be appropriately protected to secure the trust of patients and to support interoperable electronic health information exchange. This article discusses characteristics of genetic/genomic test information, including predictive capability, immutability, and uniqueness, which should be considered when developing policies about information protection. Issues related to "genetic exceptionalism"; i.e., whether genetic/genomic test information should be treated differently from other medical information for purposes of data access and permissible use, are also considered. These discussions can help guide policy that will facilitate the biological and clinical resource development to support the introduction of this information into health care.


Nuclease-mediated genome editing: At the front-line of functional genomics technology.
Genome editing with engineered endonucleases is rapidly becoming a staple method in developmental biology studies. Engineered nucleases permit random or designed genomic modification at precise loci through the stimulation of endogenous double-strand break repair. Homology-directed repair following targeted DNA damage is mediated by co-introduction of a custom repair template, allowing the derivation of knock-out and knock-in alleles in animal models previously refractory to classic gene targeting procedures. Currently there are three main types of customizable site-specific nucleases delineated by the source mechanism of DNA binding that guides nuclease activity to a genomic target: zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and clustered regularly interspaced short palindromic repeats (CRISPR). Among these genome engineering tools, characteristics such as the ease of design and construction, mechanism of inducing DNA damage, and DNA sequence specificity all differ, making their application complementary. By understanding the advantages and disadvantages of each method, one may make the best choice for their particular purpose.


Fine structure of the intersegmental membrane glands of the sixth abdominal sternum of female Nomia melanderi (Hymenoptera, Apoidea).
The fine structure of the intersegmental glands of the sixth abdominal sternum in 1-week old females of Nomia melanderi is presented. The plasma membrane of the secretory cell is unfolded in many places and is covered by a basement membrane. The microvillous surface is invaginated to form a rather long sinuous cavity. The endoplasm is almost entirely filled by secretory granules. Many secretory granules are located close to the inner surface of the invaginated plasma membrane. The invagination contains a porous ductule, apparently of cuticulin origin, that is connected directly with the inner layer of the transport duct of the duct-forming cell. This type of arrangement allows the direct flow of the secretory substance to the outside in a continuous way. The cylindrical duct-forming cell, besides having typical cell organelles, contains a cuticular transport duct. This duct is composed of a thin cuticulin layer surrounded by a rather thick epicuticular one. The results suggest that the secretory cell has two secretory cycles. The first occurs while the gland is differentiating (at the pupal stage) and is involved in secretion of the cuticulin that forms the porous ductule. The second cycle, which starts by the beginning of nesting, is involved in the secretion of a substance that is carried to the outside via the transport duct of the duct-forming cell.


Precision Health: Use of Omics to Optimize Self-Management of Chronic Pain in Aging.
Chronic pain has become a public health epidemic based on the number of Americans affected and its associated health care costs. Unfortunately, there are few efficacious treatments to manage chronic pain and as the population of older adults and centenarians who are at high risk for chronic pain continues to grow, the chronic pain epidemic will continue to worsen unless new therapeutic strategies are discovered. In the current era of precision medicine, there is a major emphasis being placed on the use of self-management and omics to discover new therapeutic targets and design treatment strategies that are tailored to the individual patient. This commentary discusses the current state of the science related to omics and self-management of chronic pain in older adults, the role of gerontological nurses in this process, and future directions. [Res Gerontol Nurs. 2018; 11(1):7-13.].


Development of Submacular Hemorrhage in Neovascular Age-related Macular Degeneration: Influence on Visual Prognosis in a Clinical Setting.
This study aimed to evaluate changes in visual acuity before and after the development of submacular hemorrhage secondary to neovascular age-related macular degeneration (AMD) and to compare the visual outcomes between patients with and without hemorrhage. This retrospective observational study included 124 patients with neovascular AMD. Patients who developed a submacular hemorrhage involving the fovea were included in the hemorrhage group (n = 55). Patients with no sign of submacular hemorrhage during the follow-up period were included in the no-hemorrhage group (n = 69). Visual outcomes were compared between the two groups. The logarithm of the minimal angle of resolution best-corrected visual acuity (BCVA) before the development of submacular hemorrhage, once the hemorrhage had developed, and 6 months after the development of hemorrhage was 0.59 ± 0.45, 1.24 ± 0.57, and 0.99 ± 0.64, respectively. BCVA was significantly worse 6 months after the hemorrhage compared to before the hemorrhage (p < 0.001). The BCVA before the development of hemorrhage (measured at a mean of 12.9 months after diagnosis) was comparable to that of the no-hemorrhage group (mean, 0.58 ± 0.37 at a mean of 12.4 months). However, the BCVA 6 months after identification of hemorrhage (mean, 21.5 months) was significantly worse in the hemorrhage group than in the no-hemorrhage group (mean, 0.73 ± 0.44 at mean 21.2 months) (p = 0.018). Visual acuity was significantly worse after hemorrhage than before hemorrhage, even after treatment. In addition, patients with submacular hemorrhage had markedly worse visual outcomes than patients without hemorrhage. This result suggests that the development of hemorrhage during the treatment course of neovascular AMD has a devastating effect on visual prognosis.


Rings, igloos, and pebbles of salt formed by drying saline drops.
It is well-known that evaporation of sessile drops with suspended particles like colloids and coffee powders can yield a variety of two-dimensional patterns depending on the particle shapes and internal flow patterns. Here we show that ordered three-dimensional structures can be built via evaporation of saline drops on highly hydrophobic substrates like pristine PP (polypropylene) with micropores and nanostructured low-surface-energy PP. On pristine PP having a high contact angle but a large contact angle hysteresis (CAH) with water, either rings or igloos of salt are formed depending on the salt concentration and evaporation rate. On nanostructured low-surface-energy PP having extreme water repellency with a very low CAH, pebbles of salt are formed regardless of salt concentration and evaporation rate. These observations lead us to conclude that combined effects of solubility, evaporation rate, and mobility of the contact line determine the final three-dimensional shape of the salt precipitate.


Hypoxia induces hypomethylation of the HMGB1 promoter via the MAPK/DNMT1/HMGB1 pathway in cardiac progenitor cells.
Apoptosis is involved in the death of cardiac progenitor cells (CPCs) after myocardial infarction (MI) in the heart. The loss of CPCs results in infarct scar and further deterioration of the heart function. Though stem cell-based therapy provides an effective approach for heart function recovery after MI, the retention of CPCs in the infarcted area of the heart is the main barrier that limits its promising therapy. Therefore, the underlying mechanisms of CPC apoptosis in hypoxia are important for the development of new therapeutic targets for MI patients. In this work, we found that the expression of high-mobility group box 1(HMGB1) was upregulated in CPCs under hypoxia conditions. Further study demonstrated that HMGB1 was regulated by DNA methyltransferases 1 (DNMT1) via changing the methylation state of CpGs in the promoter of HMGB1 in CPCs during hypoxia process. Additionally, mitogen-activated protein kinase (MAPK) signaling pathway was found to be involved in regulating DNMT1/HMGB1-mediated CPC apoptosis in hypoxia process. In conclusion, our findings demonstrate a novel regulatory mechanism for CPC apoptosis and proliferation under hypoxia conditions, which may provide a new therapeutic approach for MI patients.


Frames of reference and control parameters in visuomanual pointing.
Three hypotheses concerning the control variables in visuomanual pointing were tested. Participants pointed to a visual target presented briefly in total darkness on the horizontal plane. The starting position of the hand alternated randomly among 4 points arranged as a diamond. Results show that during the experiment, movement drifted from hypometric to hypermetric. Final positions depended on the starting position. Their average pattern reproduced the diamond of the starting points, either in same orientation (hypometric trials), or with a double inversion (hypermetric trials). The distribution of variable errors was elliptical, with the major axis aligned with the direction of the movement. Statistical analysis and Monte Carlo simulations showed that the results are incompatible with the final point control hypothesis (A. Polit & E. Bizzi, 1979). Better, but not fully satisfactory, agreement was found with the view that pointing involves comparing initial and desired postures (J. F. Soechting & M. Flanders, 1989a). The hypothesis that accounted best for the results is that final hand position is coded as a vector represented in an extrinsic frame of reference centered on the hand.


[Effects of the open method of treatment on the status of the immune system in patients with deep thermal injuries].
The condition of the immune system in 56 patients with deep thermal damage was analysed according to the method of treatment; 30 patients were treated by the traditional bandage method, 26 patients--by the open method in bed with an air cushion of the "Klinitron" type. The study showed that the introduction of beds with an air cushion into clinical practice creates the most favorable conditions for the organism's adaptation in extreme functional stress and facilitates earlier normalization of the immune status; increase of the number of "active" T lymphocytes and theophylline-resistant T lymphocytes (helpers), marked reduction of the number of theophylline-sensitive T lymphocytes (suppressors), decrease of the level of circulating immune complexes, and normalization of the immunoglobulin-E content. The positive dynamics of changes of the condition of the immune system occurred during the earlier regeneration processes and when the patients felt better.


Effects of prenatal exposure to single-wall carbon nanotubes on reproductive performance and neurodevelopment in mice.
Carbon nanotubes with extraordinary properties may become a novel drug and gene delivery tool in nanomedicine; however, insufficient information is available regarding their biosafety. Therefore, this work was performed to study the effect of prenatal exposure of single-walled carbon nanotubes (SWCNTs) on reproductive and neurobehavioral endpoints in mice. Thirty pregnant female mice were assigned to three groups (n = 10 for each group). The two treated groups were injected intraperitoneally (i.p.) with 1 or 10 mg/kg body weight (b.w.) of SWCNTs suspended in 1 ml of phosphate buffer saline (PBS) on gestational days 0 and 3. The control group was injected i.p. with an equal volume of PBS. The neurobehavioral ontogeny of pups was evaluated using a modified Fox battery. A decrease in litter size on postnatal day 2 was observed in the group treated with 10 mg/kg b.w. of SWCNTs whereas no significant differences between groups were observed in any other parameters. The behavioral development of pups did not show significant differences during growth except for the surface righting reflex, which showed significant delay compared to control in the group treated with 1 mg/kg b.w. SWCNTs. Moreover, exposed offspring (10 mg/kg b.w. SWCNTs) displayed enhanced anxiety in the elevated plus maze; however, other ethological analysis (Morris water maze and open field test) did not show behavioral changes in the experimental groups. In conclusion, the present results demonstrated small changes in offspring sensory and motor development following exposure to SWCNTs and support the idea that SWCNT risk assessment merits further investigation.


Anterior knee pain in the military population.
Anterior knee pain in our military population consititutes a diagnostic and therapeutic problem that is not always easily solved. In recent years, a better understanding of the biomechanics of the patello-femoral joint has contributed to the successful classification and treatment of many patients. However, the cause of pain remains elusive in a significant subset of patients who show no clinical or radiographic evidence of patellar malalignment and continue to have persistent pain despite adequate physiotherapy. In this article, the classification and approach to anterior knee pain are reviewed. Emphasis is placed on dividing patients into four subsets namely; normal tracking, patellar tilt, patellar subluxation and extra-articular causes of anterior knee pain. A more rational approach to the problem can then be employed and successful rehabilitation and/or surgery can be expected.


Structure-Informed Shadow Removal Networks.
Existing deep learning-based shadow removal methods still produce images with shadow remnants. These shadow remnants typically exist in homogeneous regions with low-intensity values, making them untraceable in the existing image-to-image mapping paradigm. We observe that shadows mainly degrade images at the image-structure level (in which humans perceive object shapes and continuous colors). Hence, in this paper, we propose to remove shadows at the image structure level. Based on this idea, we propose a novel structure-informed shadow removal network (StructNet) to leverage the image-structure information to address the shadow remnant problem. Specifically, StructNet first reconstructs the structure information of the input image without shadows and then uses the restored shadow-free structure prior to guiding the image-level shadow removal. StructNet contains two main novel modules: 1) a mask-guided shadow-free extraction (MSFE) module to extract image structural features in a non-shadow-to-shadow directional manner; and 2) a multi-scale feature & residual aggregation (MFRA) module to leverage the shadow-free structure information to regularize feature consistency. In addition, we also propose to extend StructNet to exploit multi-level structure information (MStructNet), to further boost the shadow removal performance with minimum computational overheads. Extensive experiments on three shadow removal benchmarks demonstrate that our method outperforms existing shadow removal methods, and our StructNet can be integrated with existing methods to improve them further.


Extreme population-dependent linkage disequilibrium detected in an inbreeding plant species, Hordeum vulgare.
In human genetics a detailed knowledge of linkage disequilibrium (LD) is considered a prerequisite for effective population-based, high-resolution gene mapping and cloning. Similar opportunities exist for plants; however, differences in breeding system and population history need to be considered. Here we report a detailed study of localized LD in different populations of an inbreeding crop species. We measured LD between and within four gene loci within the region surrounding the hardness locus in three different gene pools of barley (Hordeum vulgare). We demonstrate that LD extends to at least 212 kb in elite barley cultivars but is rapidly eroded in related inbreeding ancestral populations. Our results indicate that haplotype-based sequence analysis in multiple populations will provide new opportunities to adjust the resolution of association studies in inbreeding crop species.


4-Ports endoscopic extraperitoneal radical prostatectomy: preliminary and learning curve results.
There is a lack of studies in our national scenario regarding the results obtained by laparoscopic radical prostatectomy technique (LRP). Except for a few series, there are no consistent data on oncological, functional, and perioperative results on LRP held in Brazil. As for the LRP technique performed by extraperitoneal access (ELRP), when performed by a single surgeon, the results are even scarcer. To analyze the early perioperative and oncologic results obtained with the ELRP, throughout the technical evolution of a single surgeon. A non-randomized retrospective study was held in a Brazilian hospital of reference. In the 5-year period, 115 patients underwent the ELRP procedure. Patients were divided into two groups, the first 57 cases (Group 1) and the following 58 cases, (Group 2). A comparative analysis between the groups of efficacy results and ELRP safety was carried out. The average age of patients was 62.8 year-old and the PSA of 6.9ng/dl. The total surgery time was 135.8 minutes on average, and the urethral-bladder anastomosis was 21.9 min (23.3 min versus 20.7 min). The positive surgical margins (PSM) rate was 17.1%, showing no difference between groups (16.4% versus 17.9%; p=0.835). There was statistical difference between the groups in relation to the anastomosis time, estimated blood loss and the withdrawal time of the urinary catheter. The ELRP technique proved to be a safe and effective procedure in the treatment of prostate cancer, with low morbidity.


Epidemiology, genetics and treatment of multiple myeloma and precursor diseases.
Multiple myeloma (MM) is a hematological malignancy caused by the clonal expansion of plasma cells. The incidence of MM worldwide is increasing with greater than 140 000 people being diagnosed with MM per year. Whereas 5-year survival after a diagnosis of MM has improved from 28% in 1975 to 56% in 2012, the disease remains essentially incurable. In this review, we summarize our current understanding of MM including its epidemiology, genetics and biology. We will also provide an overview of MM management that has led to improvements in survival, including recent changes to diagnosis and therapies. Areas of unmet need include the management of patients with high-risk MM, those with reduced performance status and those refractory to standard therapies. Ongoing research into the biology and early detection of MM as well as the development of novel therapies, such as immunotherapies, has the potential to influence MM practice in the future.


An exploratory study of indicators of recent nonmedical prescription stimulant use among college students.
Objective: To explore the relationship between past 30-day nonmedical prescription stimulant use (NPSU) and past 30-day marijuana and/or alcohol use, past 30-day risky marijuana and/or alcohol use, student demographics, and student activity involvement among college students. Participants: Sample of 604 college-aged students at two large universities in the southeastern U.S. Methods: A cross-sectional survey was completed electronically. Logistic regression was used to identify and test covariates of past 30-day NPSU. Results: Over 20% of participants self-reported past NPSU. Using both marijuana and alcohol in the past 30 days (B = 3.293, p = .002, OR= 26.91, 95% CI OR= 3.42, 211.92) and engaging in both risky marijuana and alcohol use (B = 2.095, p < .001, OR = 8.13, 95% CI OR = 2.52, 25.17) were significantly related to past 30-day NPSU. Conclusions: NPSU may be indicative of broader polysubstance use problems among college-aged students.


MRI measures of fat infiltration in the lower extremities following motor incomplete spinal cord injury: reliability and potential implications for muscle activation.
Muscle fat infiltration (MFI) is an expected consequence of incomplete spinal cord injury (iSCI). The MFI magnitude may have clinical value in determining functional recovery. However, there is a lack of understanding of how MFI relates to the volitional muscle activity in people with motor incomplete spinal cord injury (iSCI). Five iSCI and 5 uninjured age-matched control subjects participated in the study. In this preliminary study, we established the reliability of MFI quantification of select lower extremity muscles across different raters. Secondly, we assessed the magnitude and distribution of MFI in the lower legs of iSCI and uninjured control participants. Thirdly, we explored the relationship between MFI in the plantar flexor muscles and the ability to volitionally activate these muscles. High levels of inter-rater reliability were observed. The iSCI group had significantly elevated and a vastly different MFI distribution in the lower leg muscles compared to healthy controls. MFI was negatively correlated with volitional activation in iSCI. Our preliminary results sanction the importance of lower extremity MFI quantification as a potential measure in determining the functional outcomes in iSCI, and the subsequent pathological sequelae.


Histamine- and stress-induced prolactin secretion: importance of vasopressin V1- and V2-receptors.
We investigated the involvement of arginine vasopressin (AVP) V1- and V2-receptors in the prolactin (PRL) secretory response to histamine (HA) or restraint stress stimulation in conscious male rats by selective blockade of AVP receptors using different antagonists. Histamine (270 nmol) administered intracerebroventricularly or 5 min of restraint stress stimulated PRL secretion 10-14-fold. Pretreatment with the selective V1-receptor antagonists [1-(p-t-butyl-beta-mercapto-beta, beta-cyclopentamethylene propionic acid)-2-(O-methyl)tyrosine-8-D-arginine]vasopressin or [1-(beta-mercapto-beta, beta-cyclopentamethylene propionic acid)-2-(O-methyl)tyrosine-8-arginine]vassopressin inhibited the PRL response to HA and restraint stress in a dose-dependent manner with maximal inhibition of 60%. The effect of the two antagonists was identical when equipotent antivasopressor doses were administered. The selective V2-receptor antagonist [1-(beta-mercapto-beta, beta-cyclopentamethylene propionic acid)-2-D-isoleucine-4-isoleucine-8-arginine]vasopressin was unable to inhibit the PRL response significantly. Combined administration of the V1-receptor antagonist [1-(p-t-butyl-beta-mercapto-beta, beta-cyclopentamethylene propionic acid-2-(O-methyl)tyrosine-8-D-arginine]vasopressin and the V2-receptor antagonist inhibited the PRL response to HA to the same extent as that observed when the V1-antagonist was administered alone. None of the antagonists used had any effect on basal PRL secretion. We conclude that AVP seems to play a role in the mediation of HA- and restraint stress-induced secretion of PRL, and that the AVP receptor involved is primarily of the V1-type or similar to this.


Epizootic vesicular stomatitis in Colorado, 1982: some observations on the possible role of wildlife populations in an enzootic maintenance cycle.
Sera obtained from wild ungulates, carnivores, and rodents in Colorado were tested for neutralizing (N) antibody against vesicular stomatitis, New Jersey serotype (VSNJ), virus to determine their involvement in the 1982 Colorado VSNJ epizootic in domestic animals. Viremic and N antibody responses of two local rodent species to a 1982 Colorado isolate of VSNJ were determined in the laboratory. The rodents produced only weak viremias, but all developed N antibody. N antibody prevalences for VSNJ in sera from wild ungulates was sufficiently high to indicate their involvement during the epizootic. In addition, the demonstration of N antibody in elk (Cervus elaphus) and mule deer (Odocoileus hemionus) prior to the epizootic in cattle and horses suggests that an enzootic cycle may exist in Colorado.


Uraba lugens (Lepidoptera: Nolidae) in New Zealand: pheromone trapping for delimitation and phenology.
A synthetic sex pheromone trapping survey of the leaf skeletonizer Uraba lugens Walker (Lepidoptera: Nolidae) demonstrated the unexpectedly widespread distribution of the insect across > 40,000 ha of urban Auckland, New Zealand. A survey of eucalyptus trees planted in parks and other public areas showed a significant spatial correlation between trap catch and breeding populations, validating the trap survey results. Traps in trees showing damage had four-fold higher catches than traps placed in undamaged or nonhost trees, and < 1% of damaged trees with traps failed to catch adult moths. Damage by larval feeding was correlated with male trap catch in the previous generation, offering good prospects for a pest management decision support system, provided that an economic threshold is developed. Catches increased by 3.4-fold in the same georeferenced trapping grid between November and December 2003 and between March and April 2004 across two generations, over the summer. A vertical transect showed that catches increased with height up to the top trap at 13 m (60% of mean tree height). Options for managing the insect will need to overcome the high rate of increase, the rate of spread, and the vertical distribution of the insect on tall eucalyptus trees.


Loss of function of Ifi202b by a microdeletion on chromosome 1 of C57BL/6J mice suppresses 11β-hydroxysteroid dehydrogenase type 1 expression and development of obesity.
Nob3 is a major obesity quantitative trait locus (QTL) identified in an intercross of New Zealand Obese (NZO) mice with C57BL/6J (B6), and by introgression of its 38 Mbp peak region into B6 (B6.NZO-Nob3.38). B6.NZO-Nob3.38 mice carrying the NZO allele exhibited markedly increased body weight, fat mass, lean mass and a lower energy expenditure, than the corresponding B6 allele carriers. For positional cloning of the responsible obesity gene, five additional congenic lines (RCS) were generated and characterized, allowing to define a critical genomic interval comprising 43 genes. mRNA profiling and western blotting indicated that Ifi202b, a member of the Ifi200 family of interferon inducible transcriptional modulators, was expressed in NZO-allele carriers but was undetectable in tissues of homozygous B6-allele carriers due to a microdeletion, including the first exon and the 5'-flanking region of Ifi202b in B6. Transcriptome analysis of adipose tissue of RCS revealed a marked induction of 11β-hydroxysteroid dehydrogenase type 1 (11β-Hsd1) expression in mice expressing Ifi202b. Furthermore, siRNA-mediated Ifi202b suppression in 3T3-L1 adipocytes resulted in a significant inhibition of 11β-Hsd1 expression, whereas an adenoviral-mediated overexpression of Ifi202b increased 11β-Hsd1 mRNA levels. Expression of human IFI orthologues was significantly increased in visceral adipose tissue of obese subjects. We suggest that the disruption of Ifi202b in B6 is responsible for the effects of the obesity QTL Nob3, and that Ifi202b modulates fat accumulation through expression of adipogenic genes such as 11β-Hsd1.


Involvement of GABA-A receptor chloride channel complex in isolation stress-induced free choice ethanol consumption in rats.
The present study revealed the effect of diazepam, a benzodiazepine, and progesterone, a pregnane precursor of neurosteroids, which act via modulating GABA-A chloride channel complex on the isolation stress-induced free choice ethanol consumption in adult rats. Isolation stress for 24 hr over a period of 6 days produced a significant increase in ethanol consumption, which persisted during the 6-day recovery period. Pretreating the animals with diazepam (5 mg/kg, i.p.), or progesterone (5 mg/kg, i.p.), blocked the isolation stress-induced increase in ethanol consumption. Bicuculline (2 mg/kg, i.p.), a GABA-A receptor antagonist significantly attenuated the effect of both diazepam and progesterone on stress-induced modulation of ethanol consumption. Isolation stress also caused an increase in total fluid consumption, which was antagonised by both diazepam and progesterone. Like ethanol consumption, this effect of diazepam and progesterone on isolation stress-induced increase in total fluid consumption was attenuated by bicuculline. Neither diazepam nor progesterone produced an increase in ethanol consumption in non-stressed rats. However, unlike diazepam, progesterone administration to non-stressed rats caused a significant increase in total fluid consumption. Results of the present study thus show that GABAergic mechanisms may be playing an important role in isolation stress-induced increase in ethanol consumption.


Antigenic nature of the chloride-stimulated cellobiosidase and other cellulases of Fibrobacter succinogenes subsp. succinogenes S85 and related fresh isolates.
Polyclonal and monoclonal antibodies to the Cl-stimulated cellobiosidase of Fibrobacter succinogenes subsp. succinogenes S85 reacted with numerous proteins of both higher and lower molecular weights from F. succinogenes subsp. succinogenes S85, but not with Escherichia coli proteins, and only one protein each from Butyrivibrio fibrisolvens and Ruminococcus albus. Different profiles were observed for Western blots (immunoblots) of peptide digests of both the purified enzyme from F. succinogenes and immunoreactive proteins of higher and lower molecular weights, demonstrating that they were different proteins. Therefore, F. succinogenes appeared to produce numerous proteins with one or more common antigenic determinants. However, with the exception of Cl-stimulated cellobiosidase, none were cellulases that have been characterized. An affinity-purified polyclonal antibody to Cl-stimulated cellobiosidase reacted with numerous proteins in cells of each of three fresh isolates of F. succinogenes subsp. succinogenes and one of F. succinogenes subsp. elongata when analyzed by Western blotting. Antibodies to periplasmic cellodextrinase, endoglucanase 2 (EG2), and EG3, when reacted in Western blots with the various cellulases, including Cl-stimulated cellobiosidase, revealed limited antigenic similarity among the different proteins and none with either B. fibrisolvens or R. albus proteins. The periplasmic cellodextrinase antibody reacted with an antigen with a size corresponding to cellodextrinase in each of the three F. succinogenes subsp. succinogenes isolates but not with any antigens from the F. succinogenes subsp. elongata isolate. The anti-EG2 antibody reacted with single antigens in each of the four isolates, while the anti-EG3 antibody reacted with only one of the four isolates.(ABSTRACT TRUNCATED AT 250 WORDS)


Effects of maternal marijuana and cocaine use on fetal growth.
To investigate the effects on infants of the use of marijuana and cocaine during pregnancy and to compare the importance of urine assays with that of interviews in ascertaining drug use, we prospectively studied 1226 mothers, recruited from a general prenatal clinic, and their infants. On the basis of either interviews or urine assays conducted prenatally or post partum, 27 percent of the subjects had used marijuana during pregnancy and 18 percent had used cocaine. When only positive urine assays were considered, the corresponding values were 16 percent and 9 percent, respectively. When potentially confounding variables were controlled for in the analysis, the infants whose mothers had positive urine assays for marijuana, as compared with the infants whose mothers were negative according to both interviews and urine assays, had a 79-g decrease in birth weight (P = 0.04) and a 0.5-cm decrement in length (P = 0.02). Women who had positive assays for cocaine, as compared with nonusers, had infants with a 93-g decrease in birth weight (P = 0.07), a 0.7-cm decrement in length (P = 0.01), and a 0.43-cm-smaller head circumference (P = 0.01). To compare our findings with those of other investigators who did not use urine assays, we repeated the analyses, considering only self-reported use of marijuana (23 percent) and cocaine (13 percent). There were no significant associations between such use as determined by interviews alone and any of the measures of outcome. We conclude that the use of marijuana or cocaine during pregnancy is associated with impaired fetal growth and that measuring a biologic marker of such use is important to demonstrate the association.


Current and future impact of technology on physiology education.
There are at least three areas in which technology can impact education: teaching, learning, and assessment. Teaching, when viewed as communication of information, has been transformed by the technology revolution. Word processing, multimedia, distance learning, and access to the World Wide Web are some prominent examples. The impact of technology on learning, defined as knowledge or skill acquired by instruction or study, has been less dramatic, in part because of our limited understanding of cognitive processes. Some forms of assessment, the collection of evidence of learning, have benefited from technology, such as item analysis of multiple-choice questions. To be effective, the focus on instruction must start with the learner and, from there, consider what should be done to enhance learning. An emphasis on what is technologically appropriate, rather than what is technologically possible, will improve the quality of both teaching and learning.


[Platelet hemostatic changes in patients with chronic alcoholism stage II in rest and exercise].
Platelet hemostasis was studied in 23 patients with chronic alcoholism (CA) stage II at rest and under muscular exercise. At rest, the patients had elevated spontaneous aggregation of platelets and more active start of adrenaline and ristomycin aggregation. Exercise stimulated spontaneous platelet aggregation, enhances adrenaline and ristomycin aggregation. According to adrenalin test 32% of the examinees had platelet dysfunction. According to ristomycin aggregation, vascular endothelium was impaired in 95.7%of the patients. Thus, it is evident that CA stage II patients develop disorder of platelet hemostasis and vascular endothelium. Such patients are at high risk of thrombogenesis.


Proteolytic inactivation of luciferases from three species of luminous marine bacteria, Beneckea harveyi, Photobacterium fischeri, and Photobacterium phosphoreum: evidence of a conserved structural feature.
Upon limited proteolysis of luciferases from the luminous marine bacteria Photobacterium fischeri, Photobacterium phosphoreum, and Beneckea harveyi, the rate of loss of luciferase activity is the same as the rate of loss of the heavier subunit of all three enzymes. It thus appears that the larger subunit of the luciferase from P. phosphoreum should be designated alpha based on its apparent homology with the alpha subunits of the luciferases from B. harveyi and P. fischeri. The luciferase from B. harveyi is more sensitive to chymotrypsin than to trypsin; the luciferases of the Photobacterium species are more sensitive to trypsin than to chymotrypsin. Proteolytic inactivation of all three luciferases results from hydrolysis of a few peptide bonds in the alpha subunit; the proteolytic fragments from the three luciferases in 0.50 M phosphate are approximately the same size, indicating that the three enzymes have a protease-labile region at about the same position in the primary structure of their alpha subunits. Phosphate stabilizes all three luciferases against inactivation by proteases. Formation and degradation of intermediate species derived from the alpha subunits are readily observable in all three luciferases. Phosphate alters both the rate of product formation and the sites of peptide bond scission. The beta subunits of the luciferases from the two Photobacterium species, unlike the enzyme of B. harveyi, appear to be degraded in buffers containing low concentrations of phosphate; in high-phosphate buffers, the beta subunits of all three luciferases appear to resist proteases. Analysis of native and chymotrypsin-inactivated P. fischeri and P. phosphoreum luciferases in the analytical ultracentrifuge indicates that, as with B. harveyi luciferase, the products of limited proteolysis do not dissociate under nondenaturing conditions. The fact that the luciferases from evolutionarily diverse species of luminous bacteria have protease-sensitive bonds in the same region of the alpha subunit that are stabilized by anions strongly suggests that the protease-labile region of the alpha subunit is either an integral component of or in close proximity to the active center.


Next-Generation Sequencing Approaches for the Identification of Pathognomonic Fusion Transcripts in Sarcomas: The Experience of the Italian ACC Sarcoma Working Group.
This work describes the set-up of a shared platform among the laboratories of the Alleanza Contro il Cancro (ACC) Italian Research Network for the identification of fusion transcripts in sarcomas by using Next Generation Sequencing (NGS). Different NGS approaches, including anchored multiplex PCR and hybrid capture-based panels, were employed to profile a large set of sarcomas of different histotypes. The analysis confirmed the reliability of NGS RNA-based approaches in detecting sarcoma-specific rearrangements. Overall, the anchored multiplex PCR assay proved to be a fast and easy-to-analyze approach for routine diagnostics laboratories.


The role of glycogen synthase kinase 3 in regulating IFN-β-mediated IL-10 production.
The ability of IFN-β to induce IL-10 production from innate immune cells is important for its anti-inflammatory properties and is believed to contribute to its therapeutic value in treating multiple sclerosis patients. In this study, we identified that IFN-β stimulates IL-10 production by activating the JAK1- and PI3K-signaling pathways. JAK1 activity was required for IFN-β to activate PI3K and Akt1 that resulted in repression of glycogen synthase kinase 3 (GSK3)-β activity. IFN-β-mediated suppression of GSK3-β promoted IL-10, because IL-10 production by IFN-β-stimulated dendritic cells (DC) expressing an active GSK3-β knockin was severely reduced, whereas pharmacological or genetic inhibition of GSK3-β augmented IL-10 production. IFN-β increased the phosphorylated levels of CREB and STAT3 but only CREB levels were affected by PI3K. Also, a knockdown in CREB, but not STAT3, affected the capacity of IFN-β to induce IL-10 from DC. IL-10 production by IFN-β-stimulated DC was shown to suppress IFN-γ and IL-17 production by myelin oligodendrocyte glycoprotein-specific CD4(+) T cells, and this IL-10-dependent anti-inflammatory effect was enhanced by directly targeting GSK3 in DC. These findings highlight how IFN-β induces IL-10 production and the importance that IL-10 plays in its anti-inflammatory properties, as well as identify a therapeutic target that could be used to increase the IL-10-dependent anti-inflammatory properties of IFN-β.


Shilnikov homoclinic orbit bifurcations in the Chua's circuit.
We analytically describe the complex scenario of homoclinic bifurcations in the Chua's circuit. We obtain a general scaling law that gives the ratio between bifurcation parameters of different nearby homoclinic orbits. As an application of this theoretical approach, we estimate the number of higher order subsidiary homoclinic orbits that appear between two consecutive lower order subsidiary orbits. Our analytical finds might be valid for a large class of dynamical systems and are numerically confirmed in the parameter space of the Chua's circuit.


The potential of adipose-derived adult stem cells as a source of neuronal progenitor cells.
Adipose-derived adult stem cells are a population of mesenchymal stem cells extracted from discarded adipose tissue. Many have reported the differentiation of adipose-derived stem cells into chondrocytes, myocytes, osteoblasts, and, most recently, neural progenitor cells. This article covers the current state of the potential of the differentiation of adipose-derived stem cells into neuronal cells and an overview of their potential as adult stem therapies for neurological disorders. It has been reported that adipose-derived stem cells are capable of undergoing neuronal differentiation using protocols similar to that of Woodbury et al., which reported the differentiation of bone marrow stromal cells specifically into neurons. However, the transdifferentiation of bone marrow stromal cells into neuronal cells has recently fallen under intense criticism, which will likely place the plasticity of adipose-derived stem cells under scrutiny as well. To date, no group has produced evidence that adipose-derived stem cells are capable of differentiating to mature, functional neuronal cells in vitro. However, recent in vivo studies with adipose-derived stem cells are promising.


Heart-Kidney Interactions in Cardiorenal Syndrome Type 1.
The exact significance of kidney function deterioration during acute decompensated heart failure (ADHF) episodes is still under debate. Several studies reported a wide percentage of worsening renal function (WRF) in ADHF patients ranging from 20% to 40%. This is probably because of different populations enrolled with different baseline kidney and cardiac function, varying definition of acute kidney injury (AKI), etiology of kidney dysfunction (KD), and occurrence of transient or permanent KD over the observational period. Current cardiorenal syndrome classification does not distinguish among the mechanisms leading to cardiac and renal deterioration. Cardiorenal syndrome type 1 (CRS-1) is the result of a combination of neurohormonal activation, fluid imbalance, arterial underfilling, increased renal and abdominal pressure, and aggressive decongestive treatment. A more complete mechanistic approach to CRS-1 should include evaluation of baseline kidney function, timing, course and magnitude of KD, and introduction of specific biomarkers able to identify early kidney damage. Therefore, clinical and laboratory parameters may yield a different combination among predisposing, precipitating, and amplifying factors that may influence cardiorenal syndrome development. Thus, CRS-1 is a heterogeneous syndrome that needs to be better defined and categorized taking into account clinical status, renal condition, and treatment. The application of universal definitions for WRF/AKI definition would be the first step to achieve a clear classification.


Sensitivity and specificity of the circulating cathodic antigen rapid urine test in the diagnosis of Schistosomiasis mansoni infection and evaluation of morbidity in a low- endemic area in Brazil.
The Kato-Katz technique is the standard diagnostic test for Schistosoma mansoni infection in rural areas. However, the utility of this method is severely limited by the day-to-day variability in host egg excretion in the stool. In high-transmission areas, the point-of-care circulating cathodic antigen (POC-CCA) urine assay has proven to be a reliable test. However, investigations of the reliability of the POC-CCA assay in low-transmission regions are under way. This study aimed to evaluate the sensitivity and specificity of the POC-CCA assay and the morbidity of schistosomiasis in a low-endemic area in Brazil. Pains City is a low-transmission zone for schistosomiasis. A total of 300 subjects aged 7-76 years were randomly selected for the POC-CCA cassette test. For S. mansoni diagnosis, three stool samples on six slides were compared with one urine sample for each subject. The sensitivity and specificity in the absence of a gold standard were calculated using latent class analysis. Clinical examinations and abdominal ultrasounds were performed in 181 volunteers to evaluate morbidity associated with schistosomiasis. The sensitivity and specificity of the Kato-Katz technique were 25.6% and 94.6%, respectively. By contrast, the sensitivity and specificity of the POC-CCA assay were 68.1% and 72.8%, respectively. Hepatosplenic schistosomiasis was diagnosed in two patients (1.1%). Overall, the POC-CCA urine assay proved to be a useful test for diagnosing S. mansoni in a low-endemic area in Brazil. Severe clinical forms of schistosomiasis can be present even in such low-endemic areas.


The effect of leucocytosis on leucocyte ascorbic acid levels.
White-blood counts, polymorph counts, leucocyte ascorbic-acid and plasma ascorbic-acid levels were measured in 91 samples of blood obtained from patients admitted to a geriatric assessment unit. There was a correlation between both white-blood counts and polymorph counts and leucocyte ascorbic-acid levels. There was no correlation between white-blood counts and polymorph counts and plasma ascorbic-acid concentrations. It is suggested that this phenomenon represents migration of ascorbate-rich polymorphs to areas of infection and infarction.


Protein Profile and Ammonia Excretion of Mud Crab <I>Scylla serrata</I> with Recirculation System.
Mud crabs have a high level of cannibalism so as to increase the growth of maximum mud crab and reduce the level of stress it is necessary environmental manipulation that supports it as a container maintenance with dark and bright conditions. This study aimed to determine the optimum container condition for survival and growth of mud crab by protein profile and ammonia excretion. Mud crab derived from the fisherman Pasuruan East Java with initial weight 45-65 g kept in containers (60×40×30 cm3) in recirculation systems for 42 days with feeding trash fish restricted by 5% twice daily. The study was conducted with two treatments and three replications of bright containers and dark containers. Several stress indicators including protein retention, total serum protein, ammonia secretion were determined and growth performance of the mud crab was also evaluated. The dark container resulted in optimum condition for mud crab indicated by the highest survival 30±6%, specific growth rate 0.44±0.02%/day, absolute longevity 1.29±0.03 cm, absolute weight growth 10.5±0.31 g, protein retention 15.59±0.46% and feed conversion ratio 6.38±0.27. This study concluded that better growth performance was observed in dark container for nursery of mud crabs.


Where do people purchase food? A novel approach to investigating food purchasing locations.
Studies exploring associations between food environments and food purchasing behaviours have been limited by the absence of data on where food purchases occur. Determining where food purchases occur relative to home and how these locations differ by individual, neighbourhood and trip characteristics is an important step to better understanding the association between food environments and food behaviours. Conducted in Melbourne, Australia, this study recruited participants within sixteen neighbourhoods that were selected based on their socioeconomic characteristics and proximity to supermarkets. The survey material contained a short questionnaire on individual and household characteristics and a food purchasing diary. Participants were asked to record details related to all food purchases made over a 2-week period including food store address. Fifty-six participants recorded a total of 952 food purchases of which 893 were considered valid for analysis. Households and food purchase locations were geocoded and the network distance between these calculated. Linear mixed models were used to determine associations between individual, neighbourhood, and trip characteristics and distance to each food purchase location from home. Additional analysis was conducted limiting the outcome to: (a) purchase made when home was the prior origin (n. 484); and (b) purchases made within supermarkets (n. 317). Food purchases occurred a median distance of 3.6 km (IQR 1.8, 7.2) from participants' homes. This distance was similar when home was reported as the origin (median 3.4 km; IQR 1.6, 6.4) whilst it was shorter for purchases made within supermarkets (median 2.8 km; IQR 1.6, 5.6). For all purchases, the reported food purchase location was further from home amongst the youngest age group (compared to the oldest age group), when workplace was the origin of the food purchase trip (compared to home), and on weekends (compared to weekdays). Differences were also observed by neighbourhood characteristics. This study has demonstrated that many food purchases occur outside what is traditionally considered the residential neighbourhood food environment. To better understand the role of food environments on food purchasing behaviours, further work is needed to develop more appropriate food environment exposure measures.


Periodontal Therapy: Patient Outcomes-Based or Profit Center-Based?
Multiple recent articles have called for outcomes-based and patient-centered guidelines for periodontal therapy.1-6 Simply put, periodontal therapy must be in accord with evidence-based treatment and doing what is right for the patient at the clinical level. With this in mind, the present authors contend that many patients with periodontal disease are not receiving acceptable and timely treatment and disease management.


Serum insulin and blood glucose levels in breast-fed and formula-fed infants in the first week of life.
Serum insulin and blood glucose levels were measured in newborns aged four to eight hours and those aged seven days who were either breast fed or formula fed. With both types of feeding, the maximum serum insulin levels occurred 60 minutes postprandially in four- to eight-hour-old infants and 30 minutes postprandially in seven-day-old babies. Between breast-fed and formula-fed groups, no statistically significant difference was found in postprandial serum insulin levels or (except for the 90-minute values on the seventh day) in blood glucose levels. It may be necessary to examine the metabolic-endocrine responses to formula administered as the only feeding over a long period to determine whether formula feeding alters such physiologic mechanisms as pancreatic function and immunity in early life and thereby affects the development of the child.


[Chronic diarrhoea in daily practice; article for education and training purposes].
Chronic diarrhoea occurs in patients of all ages and is a very common reason for patient visits to a general practitioner or medical specialist. The differential diagnosis of chronic diarrhoea is extensive and identification of the underlying cause can be challenging. In this article we answer 12 topical questions concerning the management of chronic diarrhoea in practice.


Fear of falling, falls efficacy, and health outcomes in older people following hip fracture.
This study sought to determine whether fear of falling and falls efficacy independently contribute to the prediction of health outcomes after a fall, controlling for length of stay in hospital, prefall activity problems, and history of falls. Eighty-two older people (> or = 65 years) admitted to hospital as a result of a fall, with proximal femoral fracture, were interviewed to assess variables of interest. At two months after initial interview, participants (n = 57) were re-interviewed in their own home, and their functional limitation and further fall events were assessed. Regression analyses were carried out to determine the ability of the variables assessed in hospital to predict functional limitation and further falls post discharge. Perceived risk of falling and falls efficacy did not explain variance in functional limitation when added to a model containing biomedical factors. In the prediction of further falls, addition of falls efficacy and worry over further falls to a model containing biomedical factors resulted in a statistically reliable improvement, although falls efficacy was not independently associated with outcome. Assessing worry over further falls in hospital may help to identify older people with hip fracture at risk of poor health outcomes.


Piezoelectric detection of optoacoustic spectra at cryogenic temperatures: neodymium hydroxide below 10 K.
The first piezoelectric detector for pulsed dye laser-excited optoacoustic spectroscopy of powders at cryogenic temperatures is reported. High-resolution f-f spectra of neodymium hydroxide below 10 K are presented to demonstrate its utility. Spectral simplification due to depopulation of upper Stark components of the ground state as well as significant line narrowing is observed relative to the room-temperature spectra.


Repositioning the Chemical Information Science Gateway.
The Chemical Information Science Gateway (CISG) of F1000Research was originally conceptualized as a forum for high-quality publications in chemical information science (CIS) including chemoinformatics. Adding a publication venue with open access and open peer review to the CIS field was a prime motivation for the introduction of CISG, aiming to support open science in this area. Herein, the CISG concept is revisited and the development of the gateway over the past four years is reviewed. In addition, opportunities are discussed to better position CISG within the publication spectrum of F1000Research and further increase its visibility and attractiveness for scientific contributions.


The anatomic and physiologic bases of motor-evoked potentials.
The anatomophysiologic mechanisms underlying noninvasive stimulation of brain, spinal cord, and roots via electric and magnetic impulses are surveyed. Different types of technical approaches as well as the methods for measurements of the conduction times of central motor tracts are fully described. Safety aspects are also reviewed. This new neurophysiologic technique, since its recent introduction, has explosively expanded both in its research and clinical applications.


Clinical and echocardiographic findings of patients with suspected acute pulmonary thromboembolism who underwent computed tomography pulmonary angiography.
The aim of the study was to determine the correlation between clinical and echocardiographic findings and risk factors of patients with suspected acute pulmonary thromboembolism (PTE) who underwent computed tomography pulmonary angiography (CTPA). In this cross-sectional study, 310 hospitalized patients aged >18 years with high clinical suspicion of PTE referred to imaging center of our hospital from different wards for CTPA were enrolled. The frequency of different clinical presentations, risk factors, items of Wells' criteria, and echocardiographic findings was compared in patients with and without PTE, which have been diagnosed according to the CTPA results. PTE was diagnosed in 53 (17.1%) of patients with suspected PTE. From clinical manifestations, tachypnea, pleuritic chest pain, and edema of lower extremities were significantly more frequent among patients with PTE (P < 0.05). Major surgery was the risk factor which was significantly more prevalent among patients with PTE (P < 0.05). Frequency of all criteria of Wells' criteria, except hemoptysis, was significantly higher in patients with PTE (P < 0.05). The frequency of all studied echocardiographic variables was significantly higher in patients with PTE (P < 0.05). It is suggested that we could use the results of this study for utilizing the diagnostic process of PTE in patients with highly clinical suspicion of PTE and providing more validated decision. Using the results of this study, we could identify high-risk patients and made appropriate risk assessment for better management of patients with suspected PTE as well as reduce the rate of unnecessary CTPA and its related adverse consequences.


An analysis of the legal framework influencing walking in Australia.
Although walking is a priority in many strategic plans in Australian cities, there is limited understanding of the statutory components for delivering this. Confusion still exists despite substantial evidence about the built environment elements that promote walking and the availability of tools to assess walkability outcomes. This paper examines the characteristics and components of the legal framework that influence the walkability of built environments in Australian states and territories. We audited the form and nature of statutory components regulating the design of the built environment and used framework analysis to identify and compare the main statutory instrument/s that address walkability design considerations in each state and territory. Lawmaking for planning may involve the state/territory parliament, executive, ministers, government departments and/or statutory authorities. The state/territory planning Act is the primary legislation that sets out the framework for the prevailing planning systems. Its relevance to walkability arises from its planning objectives, the legal effect it confers to statutory instruments that support the Act's implementation, and any processes or mechanisms to promote high-quality design outcomes. Most states and territories have developed jurisdiction-wide statutory tools that contain relevant design considerations for walking. These instruments influence walkability through objectives set for planning zones and aspects of development, and through criteria established to achieve the goals. Many jurisdictions use a combination of outcome and rules-based standards to achieve desired design objectives. The variability in jurisdictional approaches poses challenges, and raises uncertainty, about the scope and strength of legal support for creating walkable environments at the national level. Future policy surveillance and epidemiological analysis are needed to refine the specifications of laws that influence walking in Australia.


Default Mode Network Modulation by Psychedelics: A Systematic Review.
Psychedelics are a unique class of drug that commonly produce vivid hallucinations as well as profound psychological and mystical experiences. A grouping of interconnected brain regions characterized by increased temporal coherence at rest have been termed the Default Mode Network (DMN). The DMN has been the focus of numerous studies assessing its role in self-referencing, mind wandering, and autobiographical memories. Altered connectivity in the DMN has been associated with a range of neuropsychiatric conditions such as depression, anxiety, post-traumatic stress disorder, attention deficit hyperactive disorder, schizophrenia, and obsessive-compulsive disorder. To date, several studies have investigated how psychedelics modulate this network, but no comprehensive review, to our knowledge, has critically evaluated how major classical psychedelic agents-lysergic acid diethylamide, psilocybin, and ayahuasca-modulate the DMN. Here we present a systematic review of the knowledge base. Across psychedelics there is consistent acute disruption in resting state connectivity within the DMN and increased functional connectivity between canonical resting-state networks. Various models have been proposed to explain the cognitive mechanisms of psychedelics, and in one model DMN modulation is a central axiom. Although the DMN is consistently implicated in psychedelic studies, it is unclear how central the DMN is to the therapeutic potential of classical psychedelic agents. This article aims to provide the field with a comprehensive overview that can propel future research in such a way as to elucidate the neurocognitive mechanisms of psychedelics.


Camera-based measurement of respiratory rates is reliable.
Respiratory rate (RR) is one of the most important vital signs used to detect whether a patient is in critical condition. It is part of many risk scores and its measurement is essential for triage of patients in emergency departments. It is often not recorded as measurement is cumbersome and time-consuming. We intended to evaluate the accuracy of camera-based measurements as an alternative measurement to the current practice of manual counting. We monitored the RR of healthy male volunteers with a camera-based prototype application and simultaneously by manual counting and by capnography, which was considered the gold standard. The four assessors were mutually blinded. We simulated normoventilation, hypoventilation and hyperventilation as well as deep, normal and superficial breathing depths to assess potential clinical settings. The volunteers were assessed while being undressed, wearing a T-shirt or a winter coat. In total, 20 volunteers were included. The results of camera-based measurements of RRs and capnography were in close agreement throughout all clothing styles and respiratory patterns (Pearson's correlation coefficient, r=0.90-1.00, except for one scenario, in which the volunteer breathed slowly dressed in a winter coat r=0.84). In the winter-coat scenarios, the camera-based prototype application was superior to human counters. In our pilot study, we found that camera-based measurements delivered accurate and reliable results. Future studies need to show that camera-based measurements are a secure alternative for measuring RRs in clinical settings as well.


Defining the normal acetabular vault in adult males and females using a novel three-dimensional model.
The management and quantification of bone loss is a major challenge in primary and revision total hip replacement. Defining the normal three-dimensional (3D) anatomy of the acetabular vault could aid in assessing pathologic changes and in designing prosthetic joint components. We performed a quantitative assessment of normal 3D acetabular vault structure to define the shape and location of weight-bearing acetabular bone referred to as the vault. Images from 70 normal hip computed tomography images were used to define the 3D acetabular vault anatomy and develop a 3D model. Variation in vault shape was quantified by measuring the distance between every surface point on a subject's hemipelvis and the reference vault. Variation among different hip alignments was assessed using 19 scans from subjects with varus, valgus and dysplastic hip morphologies. The acetabular vault model had 96.6% (95% CI: 91.7-101.5), 97.8% (95% CI: 94.5-101.1) and 96.4% (95% CI: 98.7-94.1) of the surface points within 3 mm of normal male, normal female and abnormal hip specimens, respectively. Comparison of acetabular vault model fit between gender and hip types revealed that it was only significantly different between normal males and normal females (P = 0.0194) and between normal males and dysplastic females (P = 0.0377). A conserved 3D acetabular vault shape and location exists that can accommodate various hip morphologies. Defining a normal vault may increase the precision with which hip pathology can be identified and may also serve as a preoperative assessment tool for planning total hip arthroplasty.


Effect of FGF and polylactide scaffolds on calvarial bone healing with growth factor on biodegradable polymer scaffolds.
Repair of bone defects remains a major concern in reconstructive surgery. Synthetic biodegradable polymers have been used as scaffolds for guided bone regeneration. Fibroblast growth factors (FGFs) promote cell growth, differentiation, and tissue maintenance factors. They can stimulate the proliferation of osteogenic cells and chondrocytes, and also promote angiogenesis. Acidic and basic fibroblast growth factors (FGF-1 and FGF-2, respectively) are the best known members of this protein family. To evaluate the healing of experimental bone defects using poly-L/D-lactide (PLDLA) 96/4 scaffolds and FGF-1, 18 adult rats were operated on. A 6-mm diameter critical size defect (CSD) was made in the calvarial bone of each rat. The animals were divided into three treatment groups: 1) Neither scaffold nor FGF was used (control group); 2) scaffold only; and 3) scaffold with FGF-1. Follow-up time was eight weeks. Samples were embedded in methylmethacrylate and 5-microm thick sections from the middle of each specimen were stained with modified Masson-Goldner method. The shape and size of defects were evaluated radiologically. New bone formation was measured histologically and histomorphometrically. Radiologically, in the control group the shape of the defects changed from round to oval and edges were blunt. In the other groups the defects were round with sharp edges. Histomorphometrically, mean surface area of bone trabeculae was 1.05 mm (SD +/- 0.25) in group 1 (no implant), 1.35 mm (SD +/- 0.52) in group 2 (implant) and 0.79 mm (SD +/- 0.34) in group 3 (implant and FGF-1). Histological examinations revealed no or little osteoid in the groups 1 and 2, whereas in the group 3 samples had little or moderate new bone formation. Accordingly, no clear benefit of using knitted PLDLA scaffolds combined with FGF-1 on the healing of calvarial critical size defects in rats could be demonstrated.


Role of receptors of advanced glycation end-products (RAGE) in type 2 diabetic and non-diabetic individuals with chronic periodontal disease: an immunohistochemical study.
The relationship between diabetes and periodontal disease is well established. It has been shown that advanced glycation end-products might exert noxious effects on several tissues of the body through its receptor. Evidence for the role of receptors of advanced glycation end-products in periodontal disease for diabetes is limited, and their presence in human gingival tissues has been demonstrated in few studies. In this study, we demonstrate the presence of receptors of advanced glycation end-products in patients with chronic periodontitis, with and without type 2 diabetes. Gingival biopsies from 19 patients with both type 2 diabetes and chronic periodontitis, and 18 healthy controls with chronic periodontitis, were immunohistochemically stained for receptors of advanced glycation end-products. On immunohistochemical analysis, positive staining for receptors of advanced glycation end-products was seen in the endothelium and the basal and spinous layers of the inflamed gingival epithelium in both type 2 diabetes and non-diabetes tissue, with a statistically-significant difference between both groups (P <0 .05). There was a significant difference in receptors of advanced glycation end-product immune reactivity between both groups. Receptors of advanced glycation end-product increase in type 2 diabetes gingival tissue might indicate possible involvement of this receptor in periodontal destruction in individuals with type 2 diabetes.


Infected Concha Bullosa Mucocele: A Case Report.
Concha bullosa (CB) is a common sinonasal anatomic variant. The obstruction of a CB, though rare, might result in mucocele that may be misdiagnosed. In this report, we present a case of a 32-year-old female with a one-year history of unilateral nasal obstruction, headache, facial pain, foul nasal discharge, and hyposmia, initially misdiagnosed as a neoplasm. Computed tomography (CT) and magnetic resonance imaging (MRI) revealed a right middle CB infection with a mucocele. Laboratory cultures yielded Pseudomonas aeruginosa. Endoscopic sinus surgical mass excision was performed, and treatment with oral cefuroxime was administered. The patient recovered fully. A CB mucocele, though rare, should be considered in the differential diagnosis of an intranasal mass.


[A Case of Abdominal Para-Aortic Lymph Node Recurrence of Gastric Cancer Treated with Radiotherapy, Surviving More Than 5 Years].
A 66-year-old man was diagnosed with advanced type 2 gastric cancer and underwent total gastrectomy. The pathological diagnosis was T3N2H0P0CY0M0, stage ⅢB gastric cancer. Consequently, the patient received adjuvant S-1 therapy for 12 months. Thirty months after the operation, para-aortic lymph node recurrence was evident by computed tomography (CT). As a result, combination chemotherapy with paclitaxel, 5-fluorouracil, and cisplatin was initiated. However, after three courses of chemotherapy, abdominal CT showed progressive disease of the recurrent lymph node. Thereafter, radiotherapy at a total dose of 56 Gy was performed. After the radiotherapy treatment, abdominal CT demonstrated a remarkable reduction of the recurrent lymph node. The patient remains alive, with no signs of relapse, 70 months later. Therefore, this case suggests that radiotherapy may represent an effective treatment for localized remote lymph node recurrence of gastric cancer.


Thrombosis and the development of atherosclerosis: Rokitansky revisited.
In this article we have reviewed the evidence that implicates the organization and incorporation of mural thrombi as a significant component of atherosclerotic plaque growth in man. It has been emphasized that there is little or no evidence for a pathogenic role for thrombosis in plaque initiation or for the development of fatty streaks. We have suggested that the rapidly progressive category of atherosclerosis in man, as described by DeBakey, may well reflect a heightened propensity for mural or occlusive thrombosis in these patients. A broad spectrum of experimental studies examining the role of thrombosis in atherogenesis has been critically reviewed. These studies have established that experimental thrombi can become transformed into arterial fibrofatty plaques having many of the morphologic features of atherosclerosis. We have provided evidence, however, that the evolution of thrombi to fibrofatty lesions is dependent on the initial composition of the thrombi and that thrombi with a paucity of platelets and consisting predominantly of fibrin result only in fibrous intimal thickenings. The presence of hypercholesterolemia has been shown to influence the transformation of experimental thrombi. In particular, it slows the rate of thrombolysis, enhances the lipid content of the fibrofatty plaques, increases the numbers of macrophage-derived foam cells, and the frequency and extent of lesion calcification. Detailed lipid compositional studies of organizing thrombi in normolipidemic animals have shown that their lipid composition does not evolve toward the profile characteristic of atherosclerotic lesions and that the macrophage uptake of interstitial lipoproteins is probably a necessary component for the full biochemical development of the lesions.(ABSTRACT TRUNCATED AT 250 WORDS)


Utility of broad-range 16S rRNA PCR assay versus conventional methods for laboratory diagnosis of bacterial endophthalmitis in a tertiary care hospital.
Endophthalmitis, a sight-threatening intraocular infection, can be of postsurgical, post-traumatic or endogenous origin. Laboratory diagnosis-based appropriate therapy can be vision-saving. Conventional culture-based laboratory diagnosis takes time and lacks sensitivity. In this study a broad-range PCR assay was assessed against conventional and automated culture methods in vitreous specimens for accurate microbiological diagnosis. To use broad-range PCR assay targeting 16S ribosomal RNA (rRNA) region of bacteria and to assess its performance vis-à-vis conventional and automated culture methods in the laboratory diagnosis of endophthalmitis. Vitreous specimens from 195 patients with clinically diagnosed endophthalmitis were processed for classical and automated culture methods, antimicrobial sensitivity and broad-range PCR assay targeting 762 bp region of 16S rRNA followed by nucleotide sequencing by Sanger's method. Causative agents were identified from the nucleotide sequences analysed against the GenBank database, and organisms were identified using the Clinical and Laboratory Standards Institute (CLSI) MM18A guidelines. Bacteria could be detected from 127 (65.13%) of the 195 vitreous specimens by broad-range PCR assay; bacterial isolation was possible from 17 (8.7%) and 60 (30.76%) of these specimens by conventional and automated culture methods, respectively (p<0.0001). PCR assay could detect two uncultured bacterium, and in five cases the bacterial identity could not be determined from NCBI database matching. Broad-range PCR assay could provide definitive microbial diagnosis within 24 hours in significantly more patients (p<0.0001). Some rare organisms could be detected, useful in treatment modalities. Automated culture was significantly more sensitive than conventional culture.


A hereditary alteration in kidneys of mice with Chediak-Higashi syndrome.
The beige mouse is considered to be a homologue of Chediak-Higashi syndrome (CHS). Cytochemical and electron microscopic studies have revealed an inherited lesion in the kidneys of these mice. The alteration was confined to the distal segments (S3) of the proximal tubules and was characterized by the accumulation of numerous massive polysaccharide-rich granules. These granules were reactive for acid phosphatase and beta-glucuronidase activities and were therefore considered to be lysosomes. Small numbers of lymphocytes were also observed in the perivascular spaces and within the tubules of the S3 segment. The fine structure of S3 cells was also markedly altered. In addition to the massive lysosomes, dense material was found associated with the brush border and was present in pinocytotic vesicles at the base of the brush border and between basal invaginations of the plasma membranes. Despite these changes, reabsorption of exogeneous peroxidase by S3 cells appeared to be normal. The presence of a congenital defect in the kidney of the beige mouse appears to provide a useful model for studying the morphology and function of the S3 region of the nephron.


Kidney Swap in Pakistan: Experience at the Sindh Institute of Urology and Transplantation.
Kidney paired exchange is an established method of overcoming incompatibility in donor-recipient pairs and expanding the living-donor pool. It is infrequently performed in developing countries. We report the first kidney paired exchange in Pakistan, successfully performed at our center. One donor-recipient pair consisted of a 38-year-old female recipient (blood type, B positive) and her 40-year-old husband (A positive) as the potential donor. The second pair consisted of a 30-year-old male recipient (A positive) and his 30-year-old wife (B positive) as the potential donor. The donors were exchanged with the recipients, and both pairs were antigen matched for human leukocyte antigen A and human leukocyte antigen DR. Luminex antibody screening was negative, as were the crossmatches for T and B cells and for IgG and IgM. The transplant procedures and recoveries proceeded uneventfully. The recipients are maintaining serum creatinine levels around 0.78 mg/dL and 0.90 mg/dL, 1 year after transplant. Kidney paired exchange is a relatively low-cost option for overcoming the barrier of incompatibility in a resource-constrained setting.


Insertion of pulmonary artery catheters--a comparison of fiberoptic and nonfiberoptic catheters.
Fiberoptic (FO) pulmonary artery catheters were compared prospectively to the conventional type to observe the degree of insertion difficulty, the rate of complications, and the amount of technical faults. The inclusion of fiberoptic bundles in pulmonary artery catheters potentially altered their stiffness, thus influencing their passage from the central venous system to the pulmonary artery. Records were kept on the insertion of 287 consecutive pulmonary artery catheters, 44 of which contained fiberoptics for the continuous measurement of mixed-venous oxygen saturation ( SvO2 ). Results showed that the FO catheter was similar to the nonfiberoptic ( NFO ) model and could thus serve as an alternative to the conventional catheter when continuous monitoring of SvO2 was indicated.


Changes in pregnancy outcomes during the COVID-19 lockdown in Iran.
The Covid-19 pandemic response is influencing maternal and neonatal health care services especially in developing countries. However, the indirect effects of Covid-19 on pregnancy outcomes remain unknown. The aim of the present study was to compare pregnancy outcomes before and after the beginning of the Covid-19 pandemic in Iran. We performed a retrospective analysis of the medical records of 2,503 pregnant women with singleton pregnancies, admitted to the maternity department of a women's hospital in Tehran, Iran, during the pre-Covid-19 pandemic (February 19 to April 19, 2019) and the intra-Covid- 19 pandemic (February 19 to April 19, 2020) period. We included 2,503 women admitted to the hospital; 1,287 (51.4 %) were admitted before the Covid-19 lockdown and 1,216 (48.6 %) during the Covid-19 lockdown. There were no significant differences in stillbirth rates (p = 0.584) or pregnancy complications (including preeclampsia, pregnancy-induced hypertension and gestational diabetes) (p = 0.115) between pregnant women in the pre- and intra-pandemic periods. However, decreases in preterm births (p = 0.001), and low birth weight (p = 0.005) were observed in the pandemic period compared to the pre-pandemic period. No significant difference in the mode of delivery, and no maternal deaths were observed during the two time periods. In our study we observed a decrease in preterm births and low birth weight, no change in stillbirths, and a rise in the admission rates of mothers to the ICU during the initial Covid-19 lockdown period compared to pre-Covid-19 lockdown period. Further research will be needed to devise plan for immediate post-pandemic care and future health care crises.


Demand of COVID-19 medicines without prescription among community pharmacies in Jodhpur, India: Findings and implications.
COVID-19 pandemic led to increased self-medication of antimicrobials, vitamins, and immune boosters among the common people and consuming without prescription can lead to adverse consequences including antimicrobial resistance. A cross-sectional study was conducted on community pharmacies in Jodhpur, India. They were inquired regarding the prescription and increased sales (<25%, 25-50%, 50--75%, or 75--100%) of various medicines (Hydroxychloroquine, Azithromycin, Ivermectin, and Vitamin C) during the COVID-19 pandemic. Logistic regression analysis was conducted to assess the relationship between requests for certain COVID-19 medications and an increase in their sale. A total of 204 pharmacies took part, and 88.23% reported patients to approach them without prescriptions. Most of the pharmacies revealed that <25% of patients came without prescription. The majority came for azithromycin (68%) and vitamin C (92%). Increased sales of the four targeted medications were seen by 85.92% of pharmacies compared to last year. A majority (51.5%) reported <25% increased sales of azithromycin, but no change in the sale of hydroxychloroquine and ivermectin. However, 39.6% reported >75% increase in vitamin C sales. There was an increase in the demand for COVID-19 medications without prescription. This study was unable to detect a significant increase in sales of antimicrobials, which is encouraging.


The development of a marker system for Pharmacists' Behavioural Skills.
Pharmacists increasingly require complex behavioural skills to fulfil enhanced roles within healthcare teams. Behavioural marker systems are used to assess behavioural (or non-technical) skills during immersive simulation. This study aimed to develop a marker system for pharmacists' behavioural skills in patient-focussed care scenarios, and to investigate its content validity. Literature describing existing marker systems and the requisite behavioural skills of pharmacists were presented to two expert panels, alongside video examples of pharmacists in patient-focussed care simulations. The expert panels used this information to develop a new behavioural marker system. A third expert panel assessed the content validity, and the item- and scale-content validity indices were calculated. The resulting tool contains four categories, each with three or four skill elements: situation awareness (gathering information; recognising and understanding information; anticipating, preparing and planning), decision-making and prioritisation (identifying options; prioritising; dealing with uncertainty; implementing or reviewing decisions), collaborative working (involving the patient; information sharing; leadership or followership), self-awareness (role awareness; speaking up; escalating care; coping with stress). The scale-content validity index was 0.95 (ideal) and the only item below the acceptable cut-off was 'leadership or followership' (0.7). This tool is the first marker system designed to assess the behavioural skills of pharmacists in patient-focussed care scenarios. There is evidence of good content validity. It is hoped that once validated, the Pharmacists' Behavioural Skills marker system will enable pharmacy educators to provide individualised and meaningful feedback on simulation participants' behavioural skills.


Syringe-to-syringe dispersive liquid-phase microextraction solidified floating organic drop combined with high-performance liquid chromatography for the separation and quantification of ochratoxin A in food samples.
A new, simple, and rapid syringe-to-syringe dispersive liquid-phase microextraction with solidified floating organic drop was used for the separation and preconcentration of ochratoxin A from grain and juice samples before its quantification using high-performance liquid chromatography and fluorescence detection. Factors influencing the microextraction efficiency of ochratoxin A, such as sample solution pH, type and volume of organic extractant, salt concentration, number of injections, and volume of the sample, were studied and optimized. Under the optimum properties, the calibration graph showed linearity in the range of 65.0-700.0 ng/L (coefficient of determination = 0.9991). The limit of detection was 20.0 ng/L. The inter-day and intra-day relative standard deviations were in the range of 5.0-8.5%. This method was successfully applied for the quantification of ochratoxin A in grain and juice samples.


A facile and cost-effective method for separation of oil-water mixtures using polymer-coated iron oxide nanoparticles.
Catastrophic oil spills and oil from waste waters such as bilge and fracking waters pose major environmental concerns. The limitations of existing cleanup techniques for benign oil remediation has inspired a recent scientific impetus to develop oil-absorbing smart nanomaterials. Magnetic nanocomposites were here designed to allow easy recovery from various systems. In this study, sorption of reference MC252 oil with easy-to-synthesize and low-cost hydrophilic polyvinylpyrrolidone-coated iron oxide nanoparticles is reported for the first time. The one-step modified polyol synthesis in air directly generates water-soluble nanoparticles. Stable polyvinylpyrrolidone-coatings are known to minimize environmental alterations of nanoparticles from aggregation and other processes. Iron oxide provides effective magnetic actuation, while both PVP and iron oxide have low toxicity. These nanoparticles gave quantitative (near 100%) oil removal under optimized conditions. The facile synthesis and ease of use represents a significant improvement over existing techniques.


Chicken and fish diet reduces glomerular hyperfiltration in IDDM patients.
To compare the effect of a normal protein diet (test diet) in which chicken and fish were substituted for red meat with a low-protein diet (LPD) on glomerular filtration rate (GFR) in normoalbuminuric insulin-dependent-diabetes mellitus (IDDM) patients. A crossover randomized clinical trial was performed in 15 normoalbuminuric IDDM patients, 9 normofiltering, and 6 hyperfiltering patients. They followed three diets for a 3-week period each: a usual diet (UD), an LPD (0.5 g.kg-1.day-1 of proteins, 7% calories as protein, 33% as fat, and 60% as carbohydrates), and a normoproteic isocaloric test diet in which white meat (chicken and fish) was substituted for red meat of the UD. At the end of each diet, a clinical evaluation and measurements of GFR (51Cr-ethylenediaminetetraacetate (EDTA) single injection technique), urinary albumin excretion (UAE), and plasma amino acids were performed. Dietary compliance was assessed by a 24-h urinary urea and weekly interviews with the dietitian. In all diabetic patients, GFR after the LPD (114.9 +/- 16.5 ml.min-1 x 1.73 m-2) and after the test diet (122.7 +/- 16.7 ml.min-1 x 1.73 m-2) was significantly lower than after the UD (132.0 +/- 27.7 ml.min-1 x 1.73 m-2) (P = 0.001). Similar results were found in the hyperfiltering group: after UD = 161.1 +/- 15.4 ml.min-1 x 1.73 m-2, after LPD = 129.8 +/- 9.0 ml.min-1 x 1.73 m-2, and after the test diet = 136.5 +/- 3.1 ml.min-1 x 1.73 m-2, (P < 0.001). In the normofiltering group, no significant changes in GFR were observed after the three diets. Metabolic control, nutritional indexes, blood pressure (BP), and UAE did not change after the three diets in all patients. A normoproteic diet with chicken and fish as the only meat protein source decreases the GFR in the hyperfiltering normoalbuminuric IDDM patients. The GFR reduction after this diet is similar to that observed after an LPD.


Design of task-specific fluorinated ionic liquids: nanosegregation versus hydrogen-bonding ability in aqueous solutions.
We demonstrate that fluorinated ionic liquids reduce the impact of the addition of water upon the ionic liquid's H-bond acceptance ability. This is a key factor to obtain functionalized materials to be used e.g. in the dissolution of biomolecules, extraction processes or material engineering.


Prenatal drug use and the production of infant health.
We estimate the effect of illicit drug use during pregnancy on two measures of poor infant health: low birth weight and abnormal infant health conditions. We use data from a national longitudinal study of urban parents that includes postpartum interviews with mothers, hospital medical record data on the mothers and their newborns, and information about the neighborhood in which the mother resides. We address the potential endogeneity of prenatal drug use. Depending on how prenatal drug use is measured, we find that it increases low birth weight by 4-6 percentage points and that it increases the likelihood of an abnormal infant health condition by 7-12 percentage points.


A controlled trial of d-fenfluramine in bulimia nervosa.
A double-blind, placebo-controlled trial of d-fenfluramine in bulimia nervosa was undertaken in order to assess its efficacy in controlling bulimic behavior and relieving more general symptoms. A high proportion of the patients evaluated were reluctant to enter the drug trial in spite of the offer of additional supportive psychotherapy and counselling on dietary control. Moreover, 17 out of the 42 enrolled patients withdrew halfway through the 12 week trial. Were it not for this high rate of defaulting, there might be clearer support for the efficacy of d-fenfluramine in reducing the frequency of overeating and self-induced vomiting in these bulimic patients. An unexpected finding was that among the noncompleters, those on d-fenfluramine had experienced relief of their bulimic symptoms. The persistence of depressive symptoms and features of the eating disorder probably contributed to the noncompleters leaving the trial. Reassuring findings were the absence of weight loss and serious unwanted effects from d-fenfluramine. By itself, d-fenfluramine did not benefit some of the patients with severe bulimia nervosa, but it may yet prove a useful adjunct to psychological treatments.


Hyperpyrexia, allergic-type response and death occurring with low-dose bleomycin administration.
This is a case report of hyperpyrexia, shock and death following initial injection of low-dose bleomycin (7.5 units) for a poorly differentiated metastatic carcinoma. Premedication with high-dose dexamethasone and acetaminophen did not abort the reaction. A review of the literature uncovered one nearly fatal reaction to a test dose of 1 unit of bleomycin All previously reported fatal cases were in patients with lymphoma who had received an initial dose of at least 25 units/m2. Since the 'safe' test dose of bleomycin is not known, test doses of 1 unit or lower should be routinely used; the effect of premedication is also unclear.


A Retrospective Analysis of Incidental Gallbladder Cancer on Post-cholecystectomy Pathological Review.
Background Gallbladder cancer is a rare cancer with a poor prognosis despite all the advances in treatment options and is mostly detected incidentally. In the current literature, re-excision is performed on patients with stage T1b and above, but high mortality rates are still observed. In this study, we aimed to investigate the reasons affecting the prognosis of incidental gallbladder cancer. Methodology Data from 33 patients were retrospectively analyzed. Patient age, sex, preoperative radiologic findings, surgical procedures, margin status, postoperative results with histologic diagnosis, T stage, complications, and mortality were evaluated. Results Of the 33 patients included in the study, 24 (72.7%) were female, nine (27.3%) were male, and the mean age was 66.4 ± 13.4 years. Seventeen (51.5%) patients in our study were aged over 65 years. Age over 65 years was found to have a significant effect on mortality (p = 0.018). In the preoperative ultrasound imaging, 27 (81.8%) patients had gallstones, two (6.1%) patients had gallbladder polyps, 31 (93.9%) had focal or diffuse thickness increases in the gallbladder wall, and nine (27.3%) patients had pericholecystic fluid. The presence of pericholecystic fluid (p = 0.039) and wall thickness (p = 0.006) were found to be associated with mortality. There was perineural invasion and lymphovascular in 17 patients each. Both perineural invasion (p = 0.016) and lymphovascular invasion (p = 0.007) were associated with mortality. Tumor grade was also associated with mortality (p = 0.001). When the prognosis of the patients was evaluated according to the T stage, the increase in the T stage negatively affected the prognosis (p < 0.001). Overall survival was a median of 17 months (95% confidence interval = 10.6-23.3). Conclusions Incidental gallbladder cancer is detected on routine histologic examination of gallbladder specimens after cholecystectomy. Most patients may require re-excision, but the prognosis is still poor in patients who have undergone re-excision. Age >65 years, pericholecystic fluid, T stage, grade, lymphovascular invasion, and perineural invasion had a significant effect on mortality, the presence of which should trigger the option of re-excision to be examined more carefully.


A 5 year longitudinal study of water quality for final rinsing in the single chamber washer-disinfector with a reverse osmosis plant.
This report deals with the construction and management of the reverse osmosis (RO) water system for final rinsing of surgical instruments in the washer-disinfector. Numerous operational challenges were encountered in our RO water system and these were analyzed utilizing the Ishikawa Fishbone diagram. The aim was to find potential problems and promote preventive system management for RO water. It was found that the measures that existed were inappropriate for preventing contamination in the heat-labile RO water system. The storage tank was found to be significantly contaminated and had to be replaced with a new one equipped with a sampling port and water drainage system. Additional filters and an UV treatment lamp were installed. The whole system disinfection started 1.5 years later using a peracetic acid-based compound after confirming the material compatibility. Operator errors were found when a new water engineer took over the duty from his predecessor. It was also found that there were some deficiencies in the standard operating procedures (SOPs), and that on-the-job training was not enough. The water engineer failed to disinfect the sampling port and water drainage system. The RO membrane had been used for 4 years, even though the SOP standard specified changing it as every 3 years. Various bacteria, such as Rothia mucilaginosa, were cultured from the RO water sampled from the equipment. Because Rothia mucilaginosa is a resident in the oral cavity and upper respiratory tract, it is believed that the bacteria were introduced into the system by the maintenance personnel or working environment. Therefore, the presence of R. mucilaginosa implied the failure of sanitary maintenance procedures. This study suggests that water systems should be designed based on the plans for profound system maintenance. It also suggests that SOP and on-the job training are essential to avoid any operator errors. These results must be carefully considered when either constructing new RO systems or performing maintenance and periodical examination of the equipment. Reverse osmosis (RO) water is used for final rinsing in our washer-disinfector. The authors used the Ishikawa Fishbone diagram to clarify the critical points for optimizing RO water quality. There existed no measures to prevent contamination in the heat-labile RO water system. The storage tank was significantly contaminated and had to be replaced with a new one equipped with a sampling port and water drainage system. Additional filters and an UV treatment lamp were installed. The whole system disinfection started 1.5 years later using a peracetic acid-based compound after confirming the material compatibility. Operator errors occurred when a new water engineer took over the duty from his predecessor. There were neither standard operating procedures (SOPs) nor on-the-job training. The new water engineer had failed to disinfect the sampling port and water drainage system. Rothia mucilaginosa was cultured from the RO water. It is a resident in the oral cavity and upper respiratory tract. This implied the possible failure of sanitary procedures in the system maintenance. The Ishikawa Fishbone diagram was useful for this study. It suggests that water systems should be designed with plans for system maintenance taken into account. It also suggests that SOP and on-the job training are essential in order to avoid operator errors.


'Corona is coming': COVID-19 vaccination perspectives and experiences amongst Culturally and Linguistically Diverse West Australians.
Culturally and Linguistically Diverse (CALD) groups within high-income countries are at risk of being left behind by the COVID-19 vaccination rollout. They face both access and attitudinal barriers, including low trust in government and health authorities. To explore perceptions and attitudes towards COVID-19 vaccination, as well as facilitators, barriers and strategies to promote uptake among CALD residents of Western Australia (WA), where there were almost no COVID-19 cases for 2 years. Perth, WA's capital, was chosen as the state's study site because most of the state's CALD population lives there. Eleven semistructured in-depth interviews and three focus groups (with 37 participants) were conducted with CALD residents between August and October 2021. Thematic analysis was conducted, informed by the 'Capability', 'Opportunity', 'Motivation', 'Behaviour' model. CALD participants faced barriers including a lack of knowledge about COVID-19 and the vaccines, low self-rated English proficiency and education levels, misinformation, passive government communication strategies and limited access to vaccine clinics/providers. They were, however, motivated to vaccinate by the imminent opening of state and international borders, trust in government and healthcare authorities, travel intentions and the desire to protect themselves and others. Despite high levels of trust and significant desire for vaccines among CALD communities in Perth, current strategies were not meeting their needs and the community remains at risk from COVID-19. Tailored intervention strategies are required to provide knowledge, address misinformation and facilitate access to ensure uptake of COVID-19 vaccines-including for additional doses-amongst CALD communities. Governments should work with trusted CALD community members to disseminate tailored COVID-19 vaccine information and adequately translated resources. The Wesfarmers Centre of Vaccines and Infectious Diseases Community Reference Group at Telethon Kids Institute consulted on this project in September 2020; Ishar Multicultural Women's Health Services consulted on and facilitated the focus groups.


Tuberculosis in kidney transplant recipients: A case series.
Solid organ transplant recipients have an elevated risk of tuberculosis (TB) with high mortality. Data about TB in this population in the United States is sparse. We present four cases of active tuberculosis in kidney transplant recipients at our center. All patients had possible TB exposure prior to transplant and all were diagnosed with active TB within the first year of transplant. Disseminated TB was seen in half of the patients with extra-pulmonary TB being more common affecting lymph nodes, pericardium, and the kidney allograft. Delay in diagnosis from onset of symptoms ranged from fifteen days to two months. Two patients died from TB. TB is a largely preventable and curable disease. However, challenges remain in the diagnosis due to most recipients presenting with atypical symptoms. Physicians should maintain a high degree of suspicion for TB to promptly diagnose and treat post-transplant thereby minimizing complications. A review of the literature including the epidemiology, pathogenesis, clinical presentation, diagnosis and treatment options are discussed.