What Do You Know About Maryjane? A Systematic Review of the Current Data on the THC:CBD Ratio.
Background: Ratios of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) impact metabolism and therapeutic effects of cannabis. Currently, no states with legalized medical or recreational cannabis consider ratios THC:CBD in regulations. Objective: Determine what THC:CBD ratios are selected for use in clinical cannabis trials and what is the rationale. Methods: This is a systematic literature review of Central, CINAHL, Embase, PsycInfo, and PubMed of the last 10 years of English language medical cannabis publications highlighting THC:CBD ratios. Included were clinical studies of products containing and listing both THC and CBD ratios, percentages, or weighted amounts. Case reports and series, abstracts, reviews, and meta-analysis were excluded. Non-human, non-therapeutic, or studies examining approved cannabis pharmaceuticals were excluded. Results: Four hundred and seventy-nine (479) unique references were found, of which 11 met inclusion criteria. THC:CBD ratios listed and/or calculated: 1:0, 22:1, 2:1, 1:1, 1:2, 1:6, 1:9, 1:20, 1:33, 1:50, and 0:1. Rationale for ratios selected was often not listed, or simply trivialized as the ratios available to patients in the area, or ratios that were pharmaceutically available throughout the study country. One study compared ratios of high and low THC:CBD, but did not specify the ratios. Conclusion: The medical and scientific communities have not drawn substantive conclusions nor thoroughly explored THC:CBD ratios for "best practice" treatment of different disease processes and their sequelae. While there is evidence that cannabis provides medical benefits, research is lacking on standardization of medical cannabis use in modern medical practices.


A Novel Trichomonas vaginalis Surface Protein Modulates Parasite Attachment via Protein:Host Cell Proteoglycan Interaction.
Trichomonas vaginalis is a highly prevalent, sexually transmitted parasite which adheres to mucosal epithelial cells to colonize the human urogenital tract. Despite adherence being crucial for this extracellular parasite to thrive within the host, relatively little is known about the mechanisms or key molecules involved in this process. Here, we have identified and characterized a T. vaginalis hypothetical protein, TVAG_157210 (TvAD1), as a surface protein that plays an integral role in parasite adherence to the host. Quantitative proteomics revealed TvAD1 to be ∼4-fold more abundant in parasites selected for increased adherence (MA parasites) than the isogenic parental (P) parasite line. De novo modeling suggested that TvAD1 binds N-acetylglucosamine (GlcNAc), a sugar comprising host glycosaminoglycans (GAGs). Adherence assays utilizing GAG-deficient cell lines determined that host GAGs, primarily heparan sulfate (HS), mediate adherence of MA parasites to host cells. TvAD1 knockout (KO) parasites, generated using CRISPR-Cas9, were found to be significantly reduced in host cell adherence, a phenotype that is rescued by overexpression of TvAD1 in KO parasites. In contrast, there was no significant difference in parasite adherence to GAG-deficient lines by KO parasites compared with wild-type, which is contrary to that observed for KO parasites overexpressing TvAD1. Isothermal titration calorimetric (ITC) analysis showed that TvAD1 binds to HS, indicating that TvAD1 mediates host cell adherence via HS interaction. In addition to characterizing the role of TvAD1 in parasite adherence, these studies reveal a role for host GAG molecules in T. vaginalis adherence.IMPORTANCE The ability of the sexually transmitted parasite Trichomonas vaginalis to adhere to its human host is critical for establishing and maintaining an infection. Yet how parasites adhere to host cells is poorly understood. In this study, we employed a novel adherence selection method to identify proteins involved in parasite adherence to the host. This method led to the identification of a protein, with no previously known function, that is more abundant in parasites with increased capacity to bind host cells. Bioinformatic modeling and biochemical analyses revealed that this protein binds a common component on the host cell surface proteoglycans. Subsequent creation of parasites that lack this protein directly demonstrated that the protein mediates parasite adherence via an interaction with host cell proteoglycans. These findings both demonstrate a role for this protein in T. vaginalis adherence to the host and shed light on host cell molecules that participate in parasite colonization.


Covid-19's impact on supply chain decisions: Strategic insights from NASDAQ 100 firms using Twitter data.
The coronavirus pandemic is having a clear impact on the supply chains of virtually all manufacturers, retailers, and wholesalers. As the world attempts to navigate through this difficult time, most companies are struggling to maintain a steady flow of required goods and services. Whether it is frozen foods and grocery items (i.e., toilet papers), or ventilators and masks, or even the services (i.e., clinic visits), the supply chain has been facing multiple obstacles. Most models and frameworks built in the extant literature are not been able to capture these disruptions and as such, firms are not having proper strategies to deal with. For firms with complex supply chains (i.e., manufacturing, retailing), it is indeed critical to identify strategies to deal with such a crisis. In this paper, we intend to offer strategic insights in terms of major issues firms are facing and strategic options firms are contemplating. We rely on the twitter data from NASDAQ 100 firms to generate themes regarding the issues faced by the firms and the strategies they are adopting using text analytics tools. We find that firms are facing challenges in terms of demand-supply mismatch, technology, and development of a resilient supply chain. Moreover, moving beyond profitability, firms are experiencing difficulties to construct a sustainable supply chain. We provide futuristic strategic recommendations for the rebuilding of the supply chain.


The effect of inulin and resistant maltodextrin on weight loss during energy restriction: a randomised, placebo-controlled, double-blinded intervention.
The objective of this study was to investigate the additive effects of combining energy restriction with dietary fibres on change in body weight and gut microbiota composition. The study was a 12-week randomised, placebo-controlled, double-blinded, parallel intervention trial. A total of 116 overweight or obese participants were assigned randomly either to 10 g inulin plus 10 g resistant maltodextrin or to 20 g of placebo supplementation through 400 mL of milk a day, while on a - 500 kcal/day energy restricted diet. Altogether, 86 participants completed the intervention. There were no significant differences in weight loss or body composition between the groups. The fibre supplement reduced systolic (5.35 ± 2.4 mmHg, p = 0.043) and diastolic (2.82 ± 1.3 mmHg, p = 0.047) blood pressure to a larger extent than placebo. Furthermore, a larger decrease in serum insulin was observed in the placebo group compared to the fibre group (- 26.0 ± 9.2 pmol/L, p = 0.006). The intake of fibre induced changes in the composition of gut microbiota resulting in higher abundances of Parabacteroides and Bifidobacteria, compared to placebo. The effects on blood pressure and glucose metabolism were mainly observed in women, and could be attributed to a higher gut microbiota diversity after intervention. Finally, the fibre group experienced a higher degree of gastrointestinal symptoms, which attenuated over time. Supplementation of inulin and resistant maltodextrin did not provide an additional weight loss during an energy-restricted diet, but reduced both systolic and diastolic blood pressure. Furthermore, the fibre supplement did stimulate the growth of potentially beneficial bacteria genera. The study was registered at http://www.clinicaltrials.gov , NCT03135041.


Mood disorder following DBS of the left amygdaloid region in a dystonia patient with a dislodged electrode.
Continuous high-frequency stimulation of the globus pallidum internum (GPi) is an accepted treatment for patients with primary dystonia. In a series of 18 consecutive dystonia cases that were successfully treated by bilateral GPi stimulation, 1 patient had an adverse event involving the downward migration of the electrodes. He developed remarkable behavioral complications and was found to have dislodgement of the left electrode to a position close to the left amygdala. The patient developed behavioral changes consisting of depression, psychotic symptoms, and heightened pain perception. This syndrome reverted when the left electrode was removed and a new one inserted in the correct position. We describe in detail the clinical features associated with left amygdala dysregulation induced by high-frequency stimulation through the displaced electrode.


Solubilization and reconstitution of iodide counterflow activity from the thyroid plasma membranes into soybean phospholipid vesicles.
The activity of I- counterflow was solubilized with n-octyl beta-D-glucopyranoside from the thyroid plasma membranes and reconstituted into phospholipid vesicles made from soybean phospholipids by a detergent dilution procedure. The vesicles exhibited apparent "entrance" I- counterflow but no apparent Na+-dependent I- transport activity. The activity of I- counterflow was saturated by external I- at the concentration of 50-200 microM, indicating the substrate specificity of the counterflow-mediating activity for I-. The optimal concentration of the detergent for solubilization was near 12.5 mg/ml, as reported in solubilization of some sugar transport carriers of E. coli. The counterflow of I- was inhibited by externally added SCN- but not by ClO4-. When solubilized protein was treated with 0.2-1 mM dithiothreitol and with 2-10 mM 2-mercaptoethanol prior to reconstitution, dose-dependent inactivation of I- counterflow was observed. However, the activity of I- counterflow was fully preserved when solubilized protein was treated with these agents in the presence of high concentrations of I- (40 and 80 mM). In contrast, treatment with N-ethylmaleimide at a concentration of as high as 1 mM did not decrease the activity. In conclusion, it appears that the I- counterflow activity can be solubilized and reconstituted into phospholipid vesicles from the thyroid plasma membranes. The counterflow activity may be susceptible to disulfide-reducing agents.


Real-world management of juvenile autoimmune liver disease.
Juvenile autoimmune liver disease (JAILD) includes paediatric forms of autoimmune hepatitis (AIH) and autoimmune sclerosing cholangitis (ASC). Since evidence is scarce, there are currently no evidence-based management guidelines for juvenile AIH. This survey was carried out amongst the paediatric members of the International AIH Group (IAIHG) to describe their practices in the management of JAILD. An online survey questionnaire was distributed to members of the IAIHG with active practice (https://www.surveymonkey.de/r/Juvenile_AILD). The questionnaire consisted of four clinical scenarios on different presentations of AIH. Fifty-eight surveys were sent to the IAIHG members, out of which 43 (74%, 22 countries, four continents) were returned. None reported budesonide as a first-line induction agent for the acute presentation of AIH. Sixteen (37%) routinely perform liver biopsy at three years of biochemical remission. Thirty-five respondents (81%) perform magnetic resonance cholangiography (MRC) at presentation. Ciclosporin is the most widely used second-line agent (number of patients treated = ∼360, 21 centres). Mycophenolate mofetil (n = ∼225, 31 centres), tacrolimus (n = ∼130, 21 centres) and sirolimus (n = ∼5, 3 centres) are less often reported. Rescue therapy with infliximab and rituximab has been tried in eight centres (n = ∼19) and nine centres (n = ∼16), respectively. Prednisolone remains the preferred first-line induction agent in JAILD. MRC at presentation is performed by the large majority of participants. Participants reported a wide variation in performing liver biopsy for therapy evaluation during follow-up. Within the paediatric members of the IAIHG there is considerable experience with second-line therapeutic agents.


Colophonium-related Allergic Contact Dermatitis Caused by Medical Adhesive Tape Used to Prevent Skin Lesions in Soldiers.
Medical adhesive tapes are commonly recommended for the prevention of friction blisters during hiking and military marches. The aim of this paper is to report on the results of investigations into an outbreak of tape-related foot dermatitis in 26 military conscripts following continuous use of medical adhesive tapes for several days during a field exercise. Patch tests were performed using baseline series and aimed testing was performed with colophonium-related substances and different medical adhesive tapes. Contact allergy to the adhesive tapes used was found in 20 (77%) subjects, and contact allergy to colophonium in 16 (61%). Chemical analysis detected colophonium-related substances in the culprit tapes. Compared with consecutive dermatitis patients investigated at our Department of Occupational and Environmental Dermatology in the previous 10 years, conscripts with colophonium allergy had increased odds ratios for concomitant contact allergy to phenol formaldehyde resins and fragrance substances including hydroperoxides of limonene and linalool. The results show that prolonged use of medical adhesive tapes on intact skin carries a high risk for allergic contact dermatitis. Prior to their introduction on the market, medical devices should be assessed for possible side-effects.


Considerations on the mechanisms of alternating skew deviation in patients with cerebellar lesions.
Alternating skew deviation, in which the side of the higher eye changes depending upon whether gaze is directed to the left or the right, is a frequent sign in patients with posterior fossa lesions, including those restricted to the cerebellum. Here we propose a mechanism for alternating skews related to the otolith-ocular responses to fore and aft pitch of the head in lateral-eyed animals. In lateral-eyed animals the expected response to a static head pitch is cyclorotation of the eyes. But if the eyes are rotated horizontally in the orbit, away from the primary position, a compensatory skew deviation should also appear. The direction of the skew would depend upon whether the eyes were directed to the right (left eye forward, right eye backward) or to the left (left eye backward, right eye forward). In contrast, for frontal-eyed animals, skew deviations are counterproductive because they create diplopia and interfere with binocular vision. We attribute the emergence of skew deviations in frontal-eyed animals in pathological conditions to 1) an imbalance in otolithocular pathways and 2) a loss of the component of ocular motor innervation that normally corrects for the differences in pulling directions and strengths of the various ocular muscles as the eyes change position in the orbit. Such a compensatory mechanism is necessary to ensure optimal binocular visual function during and after head motion. This compensatory mechanism may depend upon the cerebellum.


Rac1 activation driven by 14-3-3ζ dimerization promotes prostate cancer cell-matrix interactions, motility and transendothelial migration.
14-3-3 proteins are ubiquitously expressed dimeric adaptor proteins that have emerged as key mediators of many cell signaling pathways in multiple cell types. Its effects are mainly mediated by binding to selective phosphoserine/threonine proteins. The importance of 14-3-3 proteins in cancer have only started to become apparent and its exact role in cancer progression as well as the mechanisms by which 14-3-3 proteins mediate cancer cell function remain unknown. While protein 14-3-3σ is widely accepted as a tumor suppressor, 14-3-3ζ, β and γ isoforms have been shown to have tumor promoting effects. Despite the importance of 14-3-3 family in mediating various cell processes, the exact role and mechanism of 14-3-3ζ remain unexplored. In the current study, we investigated the role of protein 14-3-3ζ in prostate cancer cell motility and transendothelial migration using biochemical, molecular biology and electric cell-substrate impedance sensing approaches as well as cell based functional assays. Our study indicated that expression with wild-type protein 14-3-3ζ significantly enhanced Rac activity in PC3 cells. In contrast, expression of dimer-resistant mutant of protein 14-3-3ζ (DM-14-3-3) inhibited Rac activity and associated phosphorylation of p21 activated kinase-1 and 2. Expression with wild-type 14-3-3ζ or constitutively active Rac1 enhanced extracellular matrix recognition, lamellipodia formation, cell migration and trans-endothelial migration by PC3 cells. In contrast, expression with DM 14-3-3ζ or DN-Rac1 in PC3 cells significantly inhibited these cell functions. Our results demonstrate for the first time that 14-3-3ζ enhances prostate cancer cell-matrix interactions, motility and transendothelial migration in vitro via activation of Rac1-GTPase and is an important target for therapeutic interventions for prostate cancer.


Mind injuries after cardiac surgery.
After cardiac surgery, delirium, cognitive dysfunction, depression, or anxiety disorders frequently occur, and profoundly affect patients' prognosis and quality of life. This narrative review focuses on the main clinical presentations of cognitive and psychological problems ('mind injuries') that occur postoperatively in absence of ascertainable focal neurologic deficits, exploring their pathophysiological mechanisms and possible strategies for prevention and treatment. Postoperative cognitive dysfunction is a potentially devastating complication that can involve several mechanisms and several predisposing, intraoperative, and postoperative risk factors, which can result in or be associated to cerebral microvascular damage. Postoperative depression is influenced by genetic or psychosocial predisposing factors, by neuroendocrine activation, and by the release of several pro-inflammatory factors. The net effect of these changes is neuroinflammation. These complex biochemical alterations, along with an aspecific response to stressful life events, might target the function of several brain areas, which are thought to represent a trigger factor for the onset of depression.


Penetration of new antidiabetic medications in East Asian countries and the United States: A cross-national comparative study.
The number of patients with diabetes is increasing particularly in Asia-Pacific region. Many of them are treated with antidiabetics. As the basis of the studies on the benefit and harm of antidiabetic drugs in the region, the information on patterns of market penetration of new classes of antidiabetic medications is important in providing context for subsequent research and analyzing and interpreting results. We compared penetration patterns of dipeptidyl peptidase-4 (DPP-4) inhibitors in Taiwan, Hong Kong, Japan, and the United States. We used the Taiwan National Health Insurance Research Database, a random sample of the Hong Kong Clinical Data Analysis and Reporting System, the Japan Medical Data Center database, and a 5% random sample of the US Medicare database converted to the Observational Medical Outcomes Partnership's Common Data Model to identify new users of oral antidiabetic medications. We standardized prevalence and incidence rates of medication use by age and sex to those in the 2010 Taiwanese population. We compared age, sex, comorbid conditions, and concurrent medications between new users of DPP-4 inhibitors and biguanides. Use of DPP-4 inhibitors 1 year after market entry was highest in Japan and lowest in Hong Kong. New users had more heart failure, hyperlipidemia, and renal failure than biguanide users in Taiwan, Hong Kong, and the United States while the proportions were similar in Japan. In a country with low penetration of DPP-4 inhibitors (eg, Hong Kong), users had diabetes with multiple comorbid conditions compared with biguanidine users. In a country with high penetration (eg, Japan), the proportion of users with comorbid conditions was similar to that of biguanide users. We observed a marked difference of the penetration patterns of newly marketed antidiabetics in different countries in Asia. Those results will provide the basic information useful in the future studies.


Participation of Bir1p, a member of the inhibitor of apoptosis family, in yeast chromosome segregation events.
Yeast two-hybrid and genetic interaction screens indicate that Bir1p, a yeast protein containing phylogenetically conserved antiapoptotic repeat domains called baculovirus inhibitor of apoptosis repeats (BIRs), is involved in chromosome segregation events. In the two-hybrid screen, Bir1p specifically interacts with Ndc10p, an essential component of the yeast kinetochore. Although Bir1p carries two BIR motifs in the N-terminal region, the C-terminal third of the protein is sufficient to provide strong interaction with Ndc10p and moderate interaction with Skp1p, another essential component of the yeast kinetochore. In addition, deletion of BIR1 is synthetically lethal with deletion of CBF1 or CTF19, genes specifying two other components of the yeast kinetochore. Yeast cells deleted of BIR1 have a chromosome-loss phenotype, which can be completely rescued by elevating NDC10 dosage. Furthermore, overexpression of either full-length or the C-terminal region of Bir1p can efficiently suppress the chromosome-loss phenotype of both bir1Delta null and skp1-4 mutants. Our data suggest that Bir1p participates in chromosome segregation events, either directly or via interaction with kinetochore proteins, and these effects are apparently not mediated by the BIR domains of Bir1p.


Selective occurrence of TDP-43-immunoreactive inclusions in the lower motor neurons in Machado-Joseph disease.
Pathological transactivation-responsive DNA-binding protein 43 (TDP-43) has been identified as a component of ubiquitinated inclusions in frontotemporal lobar degeneration with motor neuron disease, as well as in sporadic and some forms of familial amyotrophic lateral sclerosis. To clarify whether pathological TDP-43 is present in other neurodegenerative diseases involving the motor neuron system, we immunohistochemically examined the brain and spinal cord affected by two CAG repeat (polyglutamine) diseases, Machado-Joseph disease (MJD) and spinal and bulbar muscular atrophy (SBMA), using polyclonal antibody against TDP-43. In all the MJD cases, TDP-43-immunoreactive (ir) neuronal cytoplasmic inclusions (NCIs), although few in number, were found only in the lower motor neurons in the brainstem and spinal cord. TDP-43-ir NCIs appeared as linear wisp-like, skein-like, or thick, somewhat rod-like bodies. These inclusions were also visualized with antibodies against phosphoserines 409 and 410 of TDP-43, and ubiquitin, but were not recognized by antibody against expanded polyglutamine stretches or ataxin-3. The ultrastructure of the TDP-43-ir NCIs was similar to that of the inclusions seen in sporadic ALS, consisting of bundles of parallel filaments. None of the SBMA cases showed abnormal TDP-43 immunoreactivity in any of the regions examined. Immunoblot analysis failed to recognize hyperphosphorylated TDP-43 at ~23 kDa in two MJD cases examined. However, the immunohistochemical findings strongly suggested that in MJD, in addition to the polyglutamine-dependent disease process, TDP-43-related pathogenesis is associated with degeneration and death of the lower motor neurons.


Exposure assessment of methylmercury in samples of the BfR MEAL Study.
The BfR MEAL Study is the first German total diet study and will establish a representative and comprehensive database for dietary exposure assessment in Germany. The present study reports first results of the BfR MEAL Study regarding methylmercury in fish, seafood and mushrooms. In total, 34 MEAL foods were purchased nationally or regionally according to a defined sampling plan, prepared in a representative way for German households, pooled into 49 samples, homogenized and subjected to ICP-MS analysis. Dogfish, tuna, ocean perch, halibut and eel were the fish species with highest MeHg concentrations, while levels in mushrooms and mushroom products had markedly lower MeHg levels. Exposure was estimated by matching the present results with consumption data at appropriate levels of food group aggregation. MeHg exposure for adult high consumers (P 95) exceeded the tolerable weekly intake recommended by the European Food Safety Authority in two age groups (14-17 and 18-24 years). In children, no age group exceeded the recommended tolerable weekly intake. Regional samples differed only slightly in MeHg levels. The differences in exposure found in four regions of Germany were influenced by consumption habits rather than MeHg level in the investigated food.


Series of Fourteen Cases of Topical Imiquimod 5% in Lentigo Maligna: Treatment Modalities and Clues for Detecting Recurrences.
Topical imiquimod has been used off-label as monotherapy or adjuvant treatment for lentigo maligna. Our aim is to describe treatment modalities, clinical outcomes, and management of recurrence in patients receiving imiquimod for lentigo maligna. Patients from our unit with lentigo maligna or lentigo maligna melanoma treated with imiquimod 5% as monotherapy or in combination with surgery were included in this study. Fourteen cases were recruited (85.7% lentigo maligna and 14.3% lentigo maligna melanoma). Eight patients (57.1%) received imiquimod without surgery, and six (42.9%) underwent narrow excision before beginning treatment. During the follow-up period, pigmentation reappeared in 6 patients (4 postinflammatory hyperpigmentation and 2 relapses). Relapses were managed with very narrow excision (1mm margin) and retreatment with imiquimod 5%. All imiquimod modalities showed well-tolerated side effects and low recurrence rates, with long periods of follow-up. Imiquimod appears to be a versatile option for treating LM in suitable candidates.


The progesterone and estrogen modify the uterine prolactin and prolactin receptor expression of hyperprolactinemic mice.
The aim of this study was to evaluate the effects of metoclopramide-induced hyperprolactinemia on the prolactin (PRL) and PRL receptor's expression in the uterus of mice. For this purpose, 49 Swiss mice were divided into the following groups: GrSS (non-ovariectomized mice given vehicle); GrMET (non-ovariectomized mice treated with metoclopramide); OvSS (ovariectomized mice given vehicle); OvMET (ovariectomized mice treated with metoclopramide); OvMET+17βE (ovariectomized mice treated with metoclopramide and 17β estradiol); OvMET+MP (ovariectomized mice treated with metoclopramide and micronized progesterone); OvMET+17βE+MP (ovariectomized mice treated with metoclopramide and a solution of 17β estradiol and micronized progesterone). Immunohistochemical analyzes were evaluated semi-quantitatively. Our results showed that GrMET, OvMET+MP, and OvMET+17βE+MP presented strong PRL expression. OvMET and OvMET+17βE presented mild reaction, while GrSS and OvSS presented weak reaction. Concerning PRL receptor, OvMET+MP and OvMET+17βE+MP showed strong reaction; GrMET, OvSS, and OvMET+17βE showed mild reaction; and GrSS and OvMET showed weak reaction. These findings suggest that progesterone alone or in combination with estrogen may increase the expression of uterine PRL and PRL receptor.


New Zealand trends in corneal transplantation over the 25 years 1991-2015.
To report the 25-year longitudinal trends in indications and corneal transplantation techniques in New Zealand. Statistical analysis of prospectively acquired New Zealand National Eye Bank (NZNEB) electronic database from 1991 to 2015 inclusive. Subjects were recipients of corneal transplants in 62 centres supplied by the NZNEB. Main outcome measures were indications, recipient age and transplantation techniques. From January 1991 to December 2015, NZNEB supplied tissue for 5574 corneal transplants, increasing annually from 89 (1991) to 290 (2015). Penetrating keratoplasty remained the most commonly performed technique throughout the 25-year period, although it decreased from 98.9% of all transplants in 1991 to 60.3% in 2015. There was a corresponding increase in deep anterior lamellar and endothelial keratoplasty over the most recent decade from 2.5% to 7.2% and 4.9% to 31.4%, respectively. Keratoconus remained the leading indication for keratoplasty through to 2015 (34.5%). Regrafts (23.1%) and Fuchs endothelial corneal dystrophy (17.0%) have become more common indications, while bullous keratopathy has become less common (10.8%). There was a bimodal distribution in age with peaks at 20-29 and 60-79 years. There was a reduction in recipients under age 40 and corresponding increase in the percentage of recipients aged 40-69. Changing indications and increasing uptake of lamellar keratoplasty have been significant international trends over the last 25 years. However, New Zealand's corneal disease and population characteristics create unique longitudinal trends, with keratoconus remaining the leading indication and penetrating keratoplasty the leading technique from 1991 to 2015.


X-ray crystal structure of an IkappaBbeta x NF-kappaB p65 homodimer complex.
We report the crystal structure of a murine IkappaBbeta x NF-kappaB p65 homodimer complex. Crystallographic models were determined for two triclinic crystalline systems and refined against data at 2.5 and 2.1 A. The overall complex structure is similar to that of the IkappaBalpha.NF-kappaB p50/p65 heterodimer complex. One NF-kappaB p65 subunit nuclear localization signal clearly contacts IkappaBbeta, whereas a homologous segment from the second subunit of the homodimer is mostly solvent-exposed. The unique 47-amino acid insertion between ankyrin repeats three and four of IkappaBbeta is mostly disordered in the structure. Primary sequence analysis and differences in the mode of binding at the IkappaBbeta sixth ankyrin repeat and NF-kappaB p65 homodimer suggest a model for nuclear IkappaBbeta.NF-kappaB.DNA ternary complex formation. These unique structural features of IkappaBbeta may contribute to its ability to mediate persistent NF-kappaB activation.


Co-axis digital holography based on sinusoidal phase modulation using generalized lock-in detection.
Sinusoidal phase modulating (SPM) interferometers are used to precisely measure complex light fields with simple interferometric setups. Recently, a generalized lock-in technique has been proposed for optimizing the signal extraction in phase-modulated interferometers. This article shows its applicability in digital holography as well as digital holographic interferometry. A compact homemade setup based on the Michelson interferometer was used to observe the scattering sample surface with a spatial resolution of 32 LP/mm; out-of-plane rotation was measured with a theoretical detection limit of 0.004°. The comparison between the generalized lock-in detection and traditional SPM interferometer method was done theoretically and experimentally.


Molecular evidence of prevalent dual piroplasma infections in North American raccoons (Procyon lotor).
Based on 18S rRNA sequence analyses 2 distinct genotypes of piroplasms have been described in raccoons. One genotype resides in the Babesia sensu stricto clade and the other in the Babesia microti-like clade. Since these organisms appear morphologically indistinguishable, it is unclear which strain is responsible for the majority of the infections in raccoons. In order to overcome these limitations we performed a molecular survey of raccoons using polymerase chain reaction assays specific for each genotype. We tested blood samples from 41 wild raccoons trapped in eastern North Carolina using PCR assays and found that 95% (39/41) had detectable piroplasm DNA. Ninety percent (37/41) of the samples contained Babesia sensu stricto DNA and 83% (34/41) samples contained Babesia microti-like DNA. DNA from both genotypes was present in 76% (31/41) samples suggesting a very high rate of co-infections. The presence of dual piroplasma infections in carnivores appears to be an uncommon finding. This study highlights the need for molecular assays for the accurate identification of piroplasma. Further studies are indicated to investigate the ability of these parasites to infect domestic animals as well as their zoonotic potential.


Role of septins in the orientation of forespore membrane extension during sporulation in fission yeast.
During yeast sporulation, a forespore membrane (FSM) initiates at each spindle-pole body and extends to form the spore envelope. We used Schizosaccharomyces pombe to investigate the role of septins during this process. During the prior conjugation of haploid cells, the four vegetatively expressed septins (Spn1, Spn2, Spn3, and Spn4) coassemble at the fusion site and are necessary for its normal morphogenesis. Sporulation involves a different set of four septins (Spn2, Spn5, Spn6, and the atypical Spn7) that does not include the core subunits of the vegetative septin complex. The four sporulation septins form a complex in vitro and colocalize interdependently to a ring-shaped structure along each FSM, and septin mutations result in disoriented FSM extension. The septins and the leading-edge proteins appear to function in parallel to orient FSM extension. Spn2 and Spn7 bind to phosphatidylinositol 4-phosphate [PtdIns(4)P] in vitro, and PtdIns(4)P is enriched in the FSMs, suggesting that septins bind to the FSMs via this lipid. Cells expressing a mutant Spn2 protein unable to bind PtdIns(4)P still form extended septin structures, but these structures fail to associate with the FSMs, which are frequently disoriented. Thus, septins appear to form a scaffold that helps to guide the oriented extension of the FSM.


Combining metabolic engineering and metabolic evolution to develop nonrecombinant strains of Escherichia coli C that produce succinate and malate.
Derivatives of Escherichia coli C were engineered to produce primarily succinate or malate in mineral salts media using simple fermentations (anaerobic stirred batch with pH control) without the addition of plasmids or foreign genes. This was done by a combination of gene deletions (genetic engineering) and metabolic evolution with over 2,000 generations of growth-based selection. After deletion of the central anaerobic fermentation genes (ldhA, adhE, ackA), the pathway for malate and succinate production remained as the primary route for the regeneration of NAD+. Under anaerobic conditions, ATP production for growth was obligately coupled to malate dehydrogenase and fumarate reductase by the requirement for NADH oxidation. Selecting strains for improved growth co-selected increased production of these dicarboxylic acids. Additional deletions were introduced as further improvements (focA, pflB, poxB, mgsA). The best succinate biocatalysts, strains KJ060(ldhA, adhE, ackA, focA, pflB) and KJ073(ldhA, adhE, ackA, focA, pflB, mgsA, poxB), produce 622-733 mM of succinate with molar yields of 1.2-1.6 per mole of metabolized glucose. The best malate biocatalyst, strain KJ071(ldhA, adhE, ackA, focA, pflB, mgsA), produced 516 mM malate with molar yields of 1.4 per mole of glucose metabolized.


3D Printed "Earable" Smart Devices for Real-Time Detection of Core Body Temperature.
Real-time detection of basic physiological parameters such as blood pressure and heart rate is an important target in wearable smart devices for healthcare. Among these, the core body temperature is one of the most important basic medical indicators of fever, insomnia, fatigue, metabolic functionality, and depression. However, traditional wearable temperature sensors are based upon the measurement of skin temperature, which can vary dramatically from the true core body temperature. Here, we demonstrate a three-dimensional (3D) printed wearable "earable" smart device that is designed to be worn on the ear to track core body temperature from the tympanic membrane (i.e., ear drum) based on an infrared sensor. The device is fully integrated with data processing circuits and a wireless module for standalone functionality. Using this smart earable device, we demonstrate that the core body temperature can be accurately monitored regardless of the environment and activity of the user. In addition, a microphone and actuator are also integrated so that the device can also function as a bone conduction hearing aid. Using 3D printing as the fabrication method enables the device to be customized for the wearer for more personalized healthcare. This smart device provides an important advance in realizing personalized health care by enabling real-time monitoring of one of the most important medical parameters, core body temperature, employed in preliminary medical screening tests.


Prostate cancer: PET with 18F-FDG, 18F- or 11C-acetate, and 18F- or 11C-choline.
Prostate cancer is biologically and clinically a heterogeneous disease that makes imaging evaluation challenging. The role of imaging in prostate cancer should include diagnosis, localization, and characterization (indolent vs. lethal) of the primary tumor, determination of extracapsular spread, guidance and evaluation of local therapy in organ-confined disease, staging of locoregional lymph nodes, detection of locally recurrent and metastatic disease in biochemical relapse, planning of radiation treatment, prediction and assessment of tumor response to salvage and systemic therapy, monitoring of active surveillance and definition of a trigger for definitive therapy, and prognostication of time to hormone refractoriness in castrate disease and overall survival. To address these tasks effectively, imaging needs to be tailored to the specific phases of the disease in a patient-specific, risk-adjusted manner. In this article, I review the preclinical and clinical evidence on the potential and emerging role of PET with the 3 most commonly studied radiotracers in prostate cancer, namely 18F-FDG, 18F- or 11C-acetate, and 18F- or 11C-choline.


Current knowledge of Bartonella species.
Bartonella species are now considered emerging pathogens. Of the 11 currently recognized species, four have been implicated in human disease, although only two have been encountered in Europe. Bartonella quintana infections are now being diagnosed among the urban homeless and deprived, manifesting as trench fever, and Bartonella henselae has been shown to be the causative agent of cat scratch disease. Both species also cause a variety of HIV-associated infections, including bacillary anglomatosis. However, perhaps the most significant presentation of bartonellae infection is culture-negative endocarditis. The epidemiologies of Bartonella infections are poorly understood; most Bartonella henselae infections are probably acquired from infected cats, either directly by contact with a cat or indirectly via fleas. No animal reservoir has been implicated for Bartonella quintana; however, infection can be transmitted via the human body louse. Diagnosis of Bartonella infections can be made using histological or microbiological methods. The demonstration of specific antibodies may be useful in some instances, although certainly not in all. Cultivation of Bartonella is difficult, as the bacteria are extremely fastidious. Polymerase chain reaction-based or immunological methods for the detection of bartonella in infected tissues have proven useful. Clinical relapse is often associated with Bartonella infections despite a wide range of prescribed regimens. Only aminoglycosides display in vitro bactericidal activity against intracellular Bartonella species; therefore, they are recommended for treatment of Bartonella infections.


Assimilation: central and peripheral effects.
Assimilation and contrast have opposite effects: Contrast leads to an increase of perceived differences between neighbouring fields, whereas assimilation leads to a reduction. It is relatively easy to demonstrate these effects, but the precise localisation of these effects in the perceptual system is not yet possible. In an experiment the strength of assimilation effects was modified by adding spatial noise. By varying the localisation in perceived space of the added noise (by presentation of the noise pattern with different binocular disparities) the masking effect of this noise can be influenced. Masking caused by binocularly disparate noise is less than masking caused by binocularly non-disparate noise. It is concluded that the effect at least partly occurs beyond the (binocular) locus of separation in different depth planes. A similar approach, involving moving noise, is also presented. Finally, several demonstrations show that images that are peripherally similar can give rise to differences in the perceived amount of assimilation. These effects further indicate that a central mechanism is involved in assimilation.


Inhibition of p38 mitogen-activated protein kinase reduces inflammation after coronary vascular injury in humans.
To evaluate whether a p38α/β mitogen-activated protein kinase inhibitor, SB-681323, would limit the elevation of an inflammatory marker, high-sensitivity C-reactive protein (hsCRP), after a percutaneous coronary intervention (PCI). Coronary artery stents provide benefit by maintaining lumen patency but may incur vascular trauma and inflammation, leading to myocardial damage. A key mediator for such stress signaling is p38 mitogen-activated protein kinase. Patients with angiographically documented coronary artery disease receiving stable statin therapy and about to undergo PCI were randomly selected to receive SB-681323, 7.5 mg (n=46), or placebo (n=46) daily for 28 days, starting 3 days before PCI. On day 3, before PCI, hsCRP was decreased in the SB-681323 group relative to the placebo group (29% lower; P=0.02). After PCI, there was a statistically significant attenuation in the increase in hsCRP in the SB-681323 group relative to the placebo group (37% lower on day 5 [P=0.04]; and 40% lower on day 28 [P=0.003]). There were no adverse safety signals after 28 days of treatment with SB-681323. In the setting of statin therapy, SB-681323 significantly attenuated the post-PCI inflammatory response, as measured by hsCRP. This inflammatory dampening implicates p38 mitogen-activated protein kinase in the poststent response, potentially defining an avenue to limit poststent restenosis.


High-Resolution In Vivo Identification of miRNA Targets by Halo-Enhanced Ago2 Pull-Down.
The identification of microRNA (miRNA) targets by Ago2 crosslinking-immunoprecipitation (CLIP) methods has provided major insights into the biology of this important class of non-coding RNAs. However, these methods are technically challenging and not easily applicable to an in vivo setting. To overcome these limitations and facilitate the investigation of miRNA functions in vivo, we have developed a method based on a genetically engineered mouse harboring a conditional Halo-Ago2 allele expressed from the endogenous Ago2 locus. By using a resin conjugated to the HaloTag ligand, Ago2-miRNA-mRNA complexes can be purified from cells and tissues expressing the endogenous Halo-Ago2 allele. We demonstrate the reproducibility and sensitivity of this method in mouse embryonic stem cells, developing embryos, adult tissues, and autochthonous mouse models of human brain and lung cancers. This method and the datasets we have generated will facilitate the characterization of miRNA-mRNA networks in vivo under physiological and pathological conditions.


gamma-Aminobutyric acid receptor-regulated 36Cl- flux in mouse cortical slices.
An improved neurochemical assay for gamma-aminobutyric acid (GABA) function has been developed using tracer-radioactive chloride efflux in mouse cortical slices. Careful maintenance of the brain slice viability resulted in a 3-fold stimulation of 36Cl- efflux rate by the GABA agonist muscimol (EC50 = 3 microM), comparable to electrophysiologic and other chloride flux preparations. The shape of the muscimol dose-response curve was shallow, suggestive of negative cooperativity or heterogeneous receptors, but tissue uptake of agonist, possible diffusion barriers and apparent functional desensitization complicated these results. The response to muscimol was inhibited by GABAA receptor antagonists such as RU5135 and was enhanced by barbiturates and benzodiazepines. As observed previously, barbiturates stimulated 36Cl- efflux rate on their own and potentiated the response (potency and maximal effect) to muscimol in a stereospecific and picrotoxin-sensitive manner. Benzodiazepine receptor ligands alone did not alter 36Cl- flux, but agonists such as flunitrazepam enhanced the response to muscimol, an effect sensitive to the antagonist Ro15-1788. The inverse agonist methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate did not inhibit muscimol-activated 36Cl- flux. The anthelminthic-insecticide avermectin B1a stimulated 36Cl- flux by itself, and this response was apparently additive with that of muscimol. This brain slice chloride flux assay is therefore suitable for the assessment of activity including dose-response curves for GABAA agonists, antagonists and modulators including benzodiazepines.


[Raising of the treatment efficacy of renal colic and prophylaxis of acute calculous pyelonephritis in patient with ureterolithiasis].
In 116 patients with renal colic, caused by stones of ureters, conservative treatment with application of hyperbaric oxygenation (HBO) was conducted. Under the influence of oxygenotherapy during 3 days obstruction of the urinary tracts in all patients had disappeared as well as acute urostasis, clinic symptoms of the renal colic, progress of an acute infectious-inflammatory process stopped, complications were eliminated. Echo-positive subjects had disappeared from kidneys, in one patient renal calculus had dissolved, in 5--calculi had reduced in size and fragmentated, in 9--had not changed. In 108 patients the ureters had freed from calculi, in 8--calculi had reduced in size and migrated in distal direction.


Predictive value of heart rate recovery and peak oxygen consumption for long-term mortality in patients with coronary heart disease.
Poor exercise capacity and abnormal heart rate (HR) recovery during exercise testing predict poor long-term outcomes. The relationship between these parameters in patients with coronary heart disease (CHD) is unknown. Whether abnormal HR recovery adds to the prognostic value of poor exercise capacity in patients with CHD is unclear. A total of 282 patients (17% women) with stable CHD underwent cardiopulmonary treadmill testing at the end of Phase II cardiac rehabilitation and were followed for a mean of 9.8 +/- 2.9 years. Cox proportional hazards regression with adjustment for low peak oxygen consumption ([peak VO(2)] <19 ml/kg/min for men, <15 ml/kg/min for women), age, and gender was used to test the prognostic significance of HR recovery (HR recovery = peak - 1-minute after peak HR). HR recovery and peak VO(2) correlated mildly (r = 0.35, p <0.001). Both an abnormal HR recovery (<13 beats/min) and a low peak VO(2) were significantly associated with greater mortality in a model including age, gender, low peak VO(2), and abnormal HR recovery (hazard ratio for abnormal HR recovery = 2.16, 95% confidence interval 1.14 to 4.09; hazard ratio for low peak VO(2) = 3.63, 95% confidence interval 2.09 to 6.32). Despite a preserved peak VO(2), the 10-year mortality rate was significantly greater in patients with a HR recovery of <13 beats/min compared with those with a HR recovery of >or=13 beats/min (13.6% vs 5.6%, respectively; p <0.05). In conclusion, in patients with stable CHD undergoing cardiac rehabilitation, the rate of HR recovery provides additional prognostic information beyond the peak VO(2). An abnormal HR recovery identifies a subset of patients at intermediate risk despite a preserved peak VO(2).


Bacterial skin commensals and their role as host guardians.
Recent years' investigations of the co-evolution and functional integration of the human body and its commensal microbiota have disclosed that the microbiome has a major impact on physiological functions including protection against infections, reaction patterns in the immune system, and disposition for inflammation-mediated diseases. Two ubiquitous members of the skin microbiota, the Gram-positive bacteria Staphylococcus epidermidis and Propionibacterium acnes, are predominant on human epithelia and in sebaceous follicles, respectively. Their successful colonisation is a result of a commensal or even mutualistic lifestyle, favouring traits conferring persistency over aggressive host-damaging properties. Some bacterial properties suggest an alliance with the host to keep transient, potential pathogens at bay, such as the ability of S. epidermidis to produce antimicrobials, or the production of short-chain fatty acids by P. acnes. These features can function together with host-derived components of the innate host defence to establish and maintain the composition of a health-associated skin microbiota. However, depending largely on the host status, the relationship between the human host and S. epidermidis/P. acnes can also have parasitic features. Both microorganisms are frequently isolated from opportunistic infections. S. epidermidis is a causative agent of hospital-acquired infections, mostly associated with the use of medical devices. P. acnes is suspected to be of major importance in the pathogenesis of acne and also in a number of other opportunistic infections. In this review we will present bacterial factors and traits of these two key members of our skin microbiota and discuss how they contribute to mutualistic and parasitic properties. The elucidation of their roles in health-promoting or disease-causing processes could lead to new prophylactic and therapeutic strategies against skin disorders and other S. epidermidis/P. acnes-associated diseases, and increase our understanding of the delicate interplay of the skin microbiota with the human host.


An empirical analysis of the effect of length of forecast horizon on population forecast errors.
Many studies have found that population forecast errors generally increase with the length of the forecast horizon, but none have examined this relationship in detail. Do errors grow linearly, exponentially, or in some other manner as the forecast horizon becomes longer? Does the error-horizon relationship differ by forecasting technique, launch year, size of place, or rate of growth? Do alternative measures of error make a difference? In this article we address these questions using two simple forecasting techniques and population data from 1900 to 1980 for states in the United States. We find that in most instances there is a linear or nearly linear relationship between forecast accuracy and the length of the forecast horizon, but no consistent relationship between bias and the length of the horizon. We believe that these results provide useful information regarding the nature of population forecast errors.


American Association for Cancer Research: Clinical trials of immunotherapeutics and immunologic monitoring. April 1-5, 2000, San Francisco, CA, USA.
A major session at this annual gathering of the cancer researchers from around the globe dealt with the current state of immunotherapy for cancer. Immunotherapy is a form of cancer treatment that enhances its scientific promise and legitimacy with each passing year. As a result, this topic has become one of the most highly attended and anticipated of all the sessions during the AACR. This year's session included further progress from the laboratory to the clinic involving an ever-increasing number of cancers. For example, brain, lung and prostate cancer are now as well-represented as melanoma and lymphoma at such forums. This year's session continued the trend of impressive biosafety of both cell- and antibody-based vaccines. Therefore, these cancer vaccines offer optimism in treatment benefit as well as a minimal impact on quality of life. Lastly, the increasing number of clinical responses allows for true immunological monitoring, as scientists strive to unlock the mysteries behind what makes one patient respond to treatment and another progress. Several groups discussed in vitro immune parameters that were studied in concert with their clinical trials. Others discussed ways in which those in the immunotherapy community can work towards more reliable immune monitoring and ultimately a surrogate marker for response.


Arl13b regulates endocytic recycling traffic.
Intracellular recycling pathways play critical roles in internalizing membrane and fluid phase cargo and in balancing the inflow and outflow of membrane and cell surface molecules. To identify proteins involved in the regulation of endocytic recycling, we used an shRNA trafficking library and screened for changes in the surface expression of CD1a antigen-presenting molecules that follow an endocytic recycling route. We found that silencing of the ADP-ribosylation factor (Arf)-like small GTPase Arl13b led to a decrease in CD1a surface expression, diminished CD1a function, and delayed CD1a recycling, suggesting that Arl13b is involved in the regulation of endocytic recycling traffic. Arl13b appears to be required for the major route of endocytic trafficking, causing clustering of early endosomes and leading to the accumulation of endocytic cargo. Moreover, Arl13b colocalized with markers of the endocytic recycling pathway followed by CD1a, namely Arf6 and Rab22a. We also detected an interaction between Arl13b and the actin cytoskeleton. Arl13b was previously implicated in cilia formation and function. Our present results indicate a previously unidentified role for Arl13b in endocytic recycling traffic and suggest a link between Arl13b function and the actin cytoskeleton.


Assessing the range of enzymatic and oxidative tunability for biosensor design.
Development of multi-functional materials and biosensors that can achieve an in situ response designed by the user is a current need in the biomaterials field, especially in complex biological environments, such as inflammation, where multiple enzymatic and oxidative signals are present. In the past decade, there has been extensive research and development of materials chemistries for detecting and monitoring enzymatic activity, as well as for releasing therapeutic and diagnostic agents in regions undergoing oxidative stress. However, there has been limited development of materials in the context of enzymatic and oxidative triggers together, despite their closely tied and overlapping mechanisms. With research focusing on enzymatically and oxidatively triggered materials separately, these systems may be inadequate in monitoring the complexity of inflammatory environments, thus limiting in vivo translatability and diagnostic accuracy. The intention of this review is to highlight a variety of enzymatically and oxidatively triggered materials chemistries to draw attention to the range of synthetic tunability available for the construction of novel biosensors with a spectrum of programmed responses. We focus our discussion on several types of macromolecular sensors, generally classified by the causative material response driving ultimate signal detection. This includes sensing based on degradative processes, conformational changes, supramolecular assembly/disassembly, and nanomaterial interactions, among others. We see each of these classes providing valuable tools toward coalescing current gaps in the biosensing field regarding specificity, selectivity, sensitivity, and flexibility in application. Additionally, by considering the materials chemistry of enzymatically and oxidatively triggered biomaterials in tandem, we hope to encourage synthesis of new biosensors that capitalize on their synergistic roles and overlapping mechanisms in inflammatory environments for applications in disease diagnosis and monitoring.


Late deaths following radiotherapy for pediatric tumors.
From 1953 to 1975, 341 children received megavoltage radiation and survived at least 5 years. Chemotherapy was administered to 189 of these children. Although the expected age-adjusted 30-year survival was 97%, the observed survival was only 83%. Late recurrence of primary tumor was responsible for 24 of 37 deaths. Other causes of death included second neoplasm (4 patients), infection (4 patients), central nervous system complication (2 patients), inanition (1 patient), motor vehicle accident (1 patient), and miscellaneous (1 patient). Thus, 36 of the 37 late deaths were secondary to either the original cancer, a new cancer, or the effects of treatments. Brain tumors and Ewing's sarcoma have more late deaths while neuroblastomas have fewer late deaths than expected. Even after 25 years of follow-up, the survival of this cohort does not parallel that of the general population.


Effect of Diet Supplemented With Rapeseed Meal or Hydrolysable Tannins on the Growth, Nutrition, and Intestinal Microbiota in Grass Carp (Ctenopharyngodon idellus).
Grass carp (Ctenopharyngodon idellus; n = 320) were received four different diets for 56 days. The experimental diets were: fishmeal (FM) containing 10% fishmeal (without rapeseed meal), and rapeseed meal (RM) containing 50% rapeseed meal (without fishmeal), and two semi-purified diets either without (T0) or with 1.25% (T1) supplemental hydrolysable tannin. The approximate content of tannin in the RM diet was 1.31%, which was close to that of T1, while the tannin content of FM was close to that of T0. The weight gain rate of grass carp of the RM group was significantly lower than that of the FM group, while the feeding conversion ratio and the feeding rate were significantly higher in the T1 group than in T0. The muscle lipid content was significantly lower in RM than in FM, while T1 was lower than T0. Intestinal activities of trypsin and α-amylase were significantly higher in T1 and RM groups compared with the other treatments. The hepatic activities of aspartate aminotransferase and alanine aminotransferase were lower in T1 and RM groups compared with the other treatments, while hepatic glycogen, and malonaldehyde were significantly higher in T1 and RM groups. In serum, the total protein and globulin contents were significantly higher in T1 and RM groups, while albumin was significantly lower in the RM group compared to the FM group. High-throughput sequencing showed that Proteobacteria, Firmicutes, and Actinobacteria were the dominant bacterial phyla among groups. The intestinal microbial diversity was higher in T1 and RM. Redundancy analysis showed that tannin, rapeseed meal, and intestinal trypsin activity were positively or negatively correlated with the relative abundance of several different intestinal microbiota at phylum and/or genus levels. The results indicated that 1.25% tannin could not be the main reason for the poor growth of grass carp of the RM group; however, the protein metabolism was disturbed, the absorption of carbohydrate was improved, and the accumulation of lipid had decreased. Furthermore, tannin and rapeseed meal supplementations modulated the intestinal microbiota, and may sequentially regulate the intestinal function by fermenting dietary nutrition, producing digestive enzymes, and modulating probiotics.


The role of the near upstream sequence in hypoxia-induced expression of the erythropoietin gene.
Transcription of the erythropoietin (epo) gene is regulated in response to tissue hypoxia. In this study we show that constructs containing 117 bp of the epo promoter sequence cloned upstream of a luciferase reporter, respond to hypoxia when transfected into the human hepatoma cell line, Hep3B. The sequence -61 to -45 (EP17) relative to the transcription start of the murine epo gene imparted an approximately 4-fold induction of reporter gene expression due to hypoxia. Internal deletion of EP17 resulted in loss of induction by hypoxia without altering basal expression of the 117 bp epo promoter reporter construct. Mutagenesis studies showed that the bases at positions -53, -59, from -49 to -51 and from -55 to -57 are essential for hypoxic induction. The EP17 sequence is required for the 3' enhancer element of the epo gene to be maximally functional. Gel shift and UV cross-linking experiments showed the presence in Hep3B nuclear extracts, of two protein factors with approximate molecular weights of 52 kDa and 25 kDa that bind to EP17. Introduction of specific mutations in the EP17 region that abolish induction by hypoxia, also eliminated the binding of one or both of these factors. These experiments demonstrate a role for the proximal region of the epo promoter in hypoxic induction of the epo gene.


Plant tRNA genes: putative soybean genes for tRNAasp and tRNAmet.
We have identified cloned fragments of the soybean genome that hybridize to total soybean tRNA. Five of these clones, chosen at random, have unique patterns of restriction endonuclease sites and contain only a small region that is homologous to tRNA (less than 1 kb of 10-12 kb cloned). Two of the hybridizing fragments were subcloned and regions of about 600 bp including the homologies were sequenced. Each region contains a single putative tRNA gene, for tRNAasp or tRNAmet, surrounded by DNA rich in AT basepairs (68-82%). Neither sequence encodes the amino acid-accepting -CCA terminus. The tRNAasp gene does not contain any intervening sequences, but the tRNAmet gene has an 11-bp sequence in the anticodon loop that would not be expected in the mature tRNA. There appear to be a small number of sequences within the soybean genome that share homology with each of the regions containing a putative tRNA gene.


Evidence of Cross-Cultural Consistency of the S-Five Model for Misophonia: Psychometric Conclusions Emerging From the Mandarin Version.
Misophonia is a disorder generally characterised by a decreased tolerance to everyday sounds. Although research is increasing in misophonia, a cross-cultural validation of a psychometric tool for measuring misophonia has not been evaluated. This study investigated the validity of the S-Five multidimensional model of the misophonic experience in a sample of Chinese participants. The S-Five was translated in a forward-backward method to Mandarin to establish a satisfactory translation. The translation was also independently back translated to English, with no significant differences when compared to the original S-Five. Through exploratory factor analysis, using responses from 256 Chinese individuals, the five dimensions (internalising appraisals, externalising appraisals, perceived threat and avoidance behaviour, outbursts, and impact on functioning) were replicated, indicating the cross-cultural uniformity of the experience of misophonia as captured by the S-Five. That is, current results point to the stability of the manifestation of misophonia across cultures, seen here for the first time in the literature. By design, the S-Five items were developed to reflect sound sensitivities in a manner that is not specific or matching to individuals of a certain age, gender, ethnicity, nationality, socio-economic status, and educational level. Testimonial to this fact is not only the replication of the five factors, but also the replication of the evidence towards satisfactory psychometric properties (reliability and validity) of the scale. Based on the results of this study, the S-Five is a psychometrically robust tool to be used within the Chinese population.


Soluble Urokinase Plasminogen Activator Receptor (suPAR) Independently Predicts Severity and Length of Hospitalisation in Patients With COVID-19.
Background: Efficient healthcare based on prognostic variables in hospitalised patients with COVID-19 could reduce the risk of complications and death. Recently, soluble urokinase Plasminogen Activator Receptor (suPAR) was shown to predict respiratory failure, kidney injury, and clinical outcome in patients with SARS-CoV-2 infection. The aim of this study was to investigate the value of suPAR as a prognostic tool, in comparison with other variables, regarding disease severity and length of hospital stay in patients with COVID-19. Patients and Methods: Individuals hospitalised with COVID-19 (40 males, 20 females; median age 57.5 years) with a median symptom duration of 10 days and matched, healthy controls (n = 30) were included. Admission levels of suPAR were measured in serum by enzyme-linked immunosorbent assay. Blood cell counts, C-reactive protein (CRP) levels, lactate dehydrogenase (LDH), plasma creatinine and estimated glomerular filtration rates were analysed and oxygen demand, level of care and length of hospitalisation recorded. Results: Patients had significantly higher suPAR levels compared to controls (P < 0.001). Levels were higher in severely/critically (median 6.6 ng/mL) compared with moderately ill patients (median 5.0 ng/mL; P = 0.002). In addition, suPAR levels correlated with length of hospitalisation (rho = 0.35; P = 0.006). Besides suPAR, LDH, CRP, neutrophil count, neutrophil-to-monocyte and neutrophil-to-lymphocyte ratio, body mass index and chronic renal failure were discriminators of COVID-19 severity and/or predictors of length of hospitalisation. Conclusion: Admission levels of suPAR were higher in patients who developed severe/critical COVID-19 and associated with length of hospital stay. In addition, we showed that suPAR functioned as an independent predictor of COVID-19 disease severity.


Sphingobium algorifonticola sp. nov., isolated from a cold spring.
Strain TLA-22T, isolated from a cold spring in Taiwan, was characterized using a polyphasic taxonomy approach. Cells were Gram-stain-negative, aerobic, poly-β-hydroxybutyrate-accumulating, motile by means of a single polar flagellum, rod-shaped and formed bright yellow colonies. Optimal growth occurred at 20-25 °C, pH 6-6.5, and in the presence of 0.5 % NaCl. The major fatty acids of TLA-22T were C18 : 1 ω7 c and C17 : 1ω6c. The predominant hydroxy fatty acids were C15 : 0 2-OH and C14 : 0 2-OH. The polar lipid profile consisted of a mixture of phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, phosphatidyldimethylethanolamine, sphingoglycolipid, an unidentified aminophospholipid, an unidentified phospholipid and three unidentified lipids. TLA-22T contained spermidine as the major polyamine and putrescine as the minor component. The only isoprenoid quinone was Q-10. The genomic DNA G+C content of TLA-22T was 63.2 mol%. Phylogenetic analyses based on 16S rRNA gene sequences and coding sequences of 92 protein clusters indicated that TLA-22T was a mem,ber of a phylogenetic lineage including members of the genus Sphingobium. TLA-22T was most closely related to Sphingobium aromaticiconvertens RW16T, with a 97.4 % 16S rRNA gene sequence similarity. TLA-22T showed 74.8-75.7 % average nucleotide identity and 20.1-22.0 % digital DNA-DNA hybridization identity with the strains of other species of the genus Sphingobium. On the basis of phenotypic and genotypic properties and phylogenetic inference, strain TLA-22T should be classified as representing a novel species of the genus Sphingobium, for which the name Sphingobium algorifonticola sp. nov. is proposed. The type strain is TLA-22T (=BCRC 81097T =LMG 30309T=KCTC 62189T).


The transition of elderly patients between hospitals and nursing homes. Improving nurse-to-nurse communication.
Lack of patient information is a particular problem when a patient is transferred from one health care facility to another. The lack of information needed to develop a timely and effective plan of care for an older adult transferred to the nursing home facility may exacerbate disruptions in the older adult's care. Also, adjustment or readjustment to the nursing home or hospital environment may be prolonged. Persistence of problems or difficulty in adjustment may then lead to exacerbation of the disease processes and, ultimately, hospital readmissions. Evidence suggests that elderly patients discharged from the hospital have high readmission rates. Although the patient is most affected by a breakdown in communication, everyone in the nursing home involved in the resident's care is also affected. All staff who provide care to the resident, including nursing, medicine, nutrition, pharmacy, social work, and physical therapy staff members, must be cognizant of issues related to communication for patients being transferred. In this article, the authors discuss the development, implementation, and results of a model designed to increase the communication surrounding the transition of elderly patients from an inpatient unit to and from nursing homes.


[2,4,6-trinitrotoluene as a nutritional source for bacteria].
2,4,6-Trinitrotoluene (TNT) is one of the most stable toxic substances belonging to nitroaryls which is introduced into water reservoirs with industrial wastes. Its metabolism by microorganisms was studied in this work. The nitrogen of TNT is less accessible for Pseudomonas denitrificans than for Escherichia coli. In the latter case, TNT can be compared with ammonium sulphate. As a source of carbon, TNT is not utilized at all by E. coli and is hardly accessible for Ps. denitrificans. The data obtained in this work are valuable for intensifying the decomposition of TNT in natural and waste waters. This process can be stimulated in the conditions of biological purification of waters by combining waste waters containing TNT with other industrial waters containing accessible organic substances.


Protective effect of human granulocyte colony-stimulating factor on microbial infection in neutropenic mice.
A purified human granulocyte colony-stimulating factor (hG-CSF) was studied for its protective effect on the induction of neutropenia and enhanced susceptibility to microbial infections in mice receiving cyclophosphamide (CPA). A severe reduction in peripheral blood neutrophils was induced 4 days after injection with 200 mg of CPA per kg although the level normalized rapidly thereafter. When mice were injected subcutaneously once a day with 2.5 micrograms of hG-CSF beginning on the day after CPA injection, the reduction was prevented markedly, even 4 days later. On the other hand, in mice receiving CPA 4 days prior to infection, a weakened resistance to intraperitoneal challenge with a strain of Pseudomonas aeruginosa was induced. This weakened resistance was dose-dependently restored to normal by four daily injections with hG-CSF. A daily dose of 1.0 microgram was required for complete restoration, although hG-CSF did not directly inhibit bacterial growth in vitro. In hG-CSF-treated mice, morphologically mature neutrophils migrated rapidly into the peritoneal cavities where bacteria were inoculated, followed by a rapid elimination of bacteria from the locality as compared with controls. In addition, the same treatment with hG-CSF was able to protect significantly against systemic infections caused by Serratia marcescens, Escherichia coli, Staphylococcus aureus, and Candida albicans. These data show the possibility that prophylactic therapy with hG-CSF may augment the resistance of immunocompromised patients to infections.


De novo mutations in ATP1A3 cause alternating hemiplegia of childhood.
Alternating hemiplegia of childhood (AHC) is a rare, severe neurodevelopmental syndrome characterized by recurrent hemiplegic episodes and distinct neurological manifestations. AHC is usually a sporadic disorder and has unknown etiology. We used exome sequencing of seven patients with AHC and their unaffected parents to identify de novo nonsynonymous mutations in ATP1A3 in all seven individuals. In a subsequent sequence analysis of ATP1A3 in 98 other patients with AHC, we found that ATP1A3 mutations were likely to be responsible for at least 74% of the cases; we also identified one inherited mutation in a case of familial AHC. Notably, most AHC cases are caused by one of seven recurrent ATP1A3 mutations, one of which was observed in 36 patients. Unlike ATP1A3 mutations that cause rapid-onset dystonia-parkinsonism, AHC-causing mutations in this gene caused consistent reductions in ATPase activity without affecting the level of protein expression. This work identifies de novo ATP1A3 mutations as the primary cause of AHC and offers insight into disease pathophysiology by expanding the spectrum of phenotypes associated with mutations in ATP1A3.


Metagenomic assessment of the interplay between the environment and the genetic diversification of Acinetobacter.
Most bacteria have poorly characterized environmental reservoirs and unknown closely related species. This hampers the study of bacterial evolutionary ecology because both the environment and the genetic background of ancestral lineages are unknown. We combined metagenomics, comparative genomics and phylogenomics to overcome this limitation, to identify novel taxa and to propose environments where they can be isolated. We applied this method to characterize the ecological distribution of known and novel lineages of Acinetobacter spp. We observed two major environmental transitions at deep phylogenetic levels, splitting the genus into three ecologically differentiated clades. One of these has rapidly shifted towards host-association by acquiring genes involved in bacteria-eukaryote interactions. We show that environmental perturbations affect species distribution in predictable ways: bovines have very diverse communities of Acinetobacter, unless they were administered antibiotics, in which case they show highly uniform communities of Acinetobacter spp. that resemble those of humans. Our results uncover the diversity of bacterial lineages, overpassing the limitations of classical cultivation methods and highlight the role of the environment in shaping their evolution.


Does mesoscopic elasticity control viscous slowing down in glassforming liquids?
The dramatic slowing down of relaxation dynamics of liquids approaching the glass transition remains a highly debated problem, where the crux of the puzzle resides in the elusive increase in the activation barrier ΔE(T) with decreasing temperature T. A class of theoretical frameworks-known as elastic models-attribute this temperature dependence to the variations of the liquid's macroscopic elasticity, quantified by the high-frequency shear modulus G∞(T). While elastic models find some support in a number of experimental studies, these models do not take into account the spatial structures, length scales, and heterogeneity associated with structural relaxation in supercooled liquids. Here, we propose and test the possibility that viscous slowing down is controlled by a mesoscopic elastic stiffness κ(T), defined as the characteristic stiffness of response fields to local dipole forces in the liquid's underlying inherent structures. First, we show that κ(T)-which is intimately related to the energy and length scales characterizing quasilocalized, nonphononic excitations in glasses-increases more strongly with decreasing T than the macroscopic inherent structure shear modulus G(T) [the glass counterpart of liquids' G∞(T)] in several computer liquids. Second, we show that the simple relation ΔE(T) ∝ κ(T) holds remarkably well for some computer liquids, suggesting a direct connection between the liquid's underlying mesoscopic elasticity and enthalpic energy barriers. On the other hand, we show that for other computer liquids, the above relation fails. Finally, we provide strong evidence that what distinguishes computer liquids in which the ΔE(T) ∝ κ(T) relation holds from those in which it does not is that the latter feature highly fragmented/granular potential energy landscapes, where many sub-basins separated by low activation barriers exist. Under such conditions, it appears that the sub-basins do not properly represent the landscape properties relevant for structural relaxation.


Cyclic AMP-dependent protein kinase but not protein kinase C regulates the cardiac Ca2+ channel through phosphorylation of its alpha 1 subunit.
The voltage-dependent L-type Ca2+ channel in the heart is regulated by cAMP-dependent protein kinase (PKA) and possibly by protein kinase C (PKC). We have investigated the channel modulation through phosphorylation by these protein kinases, using liposomes into which Ca2+ channels from bovine heart were reconstituted. Phosphorylation of the proteoliposomes with PKA increased the dihydropyridine-sensitive Ca2+ efflux from them by about 70%. PKA rapidly phosphorylated membrane proteins of 210 and 170 kDa. A dihydropyridine-class Ca2+ channel blocker, [3H]azidopine, specifically photo-labeled a protein of 210 kDa, suggesting that the 210-kDa phosphoprotein might be the alpha 1 subunit of the Ca2+ channel. In contrast, phosphorylation of the proteoliposomes with PKC failed to modulate the Ca2+ efflux. Although PKC catalyzed the phosphorylation of membrane proteins of 150, 130, 95, 67, and 62 kDa, the 210- and 170-kDa proteins were not phosphorylated by this kinase. These results suggest that phosphorylation of the 210-kDa protein in the cardiac sarcolemma by PKA may be responsible for modulation of the channel function, whereas modulation of the channel by PKC, if it occurs, must be the result of an indirect mechanism, e.g. phosphorylation of a cytoplasmic protein or an associated channel polypeptide, that cannot function in the reconstituted system.


Insight into the architecture of the NuRD complex: structure of the RbAp48-MTA1 subcomplex.
The nucleosome remodeling and deacetylase (NuRD) complex is a widely conserved transcriptional co-regulator that harbors both nucleosome remodeling and histone deacetylase activities. It plays a critical role in the early stages of ES cell differentiation and the reprogramming of somatic to induced pluripotent stem cells. Abnormalities in several NuRD proteins are associated with cancer and aging. We have investigated the architecture of NuRD by determining the structure of a subcomplex comprising RbAp48 and MTA1. Surprisingly, RbAp48 recognizes MTA1 using the same site that it uses to bind histone H4, showing that assembly into NuRD modulates RbAp46/48 interactions with histones. Taken together with other results, our data show that the MTA proteins act as scaffolds for NuRD complex assembly. We further show that the RbAp48-MTA1 interaction is essential for the in vivo integration of RbAp46/48 into the NuRD complex.


Child development and evolutionary psychology.
Evolutionary developmental psychology involves the expression of evolved, epigenetic programs, as described by the developmental systems approach, over the course of ontogeny. There have been different selection pressures on organisms at different times in ontogeny, and some characteristics of infants and children were selected in evolution to serve an adaptive function at that time in their life history rather than to prepare individuals for later adulthood. Examples of such adaptive functions of immaturity are provided from infancy, play, and cognitive development. Most evolved psychological mechanisms are proposed to be domain specific in nature and have been identified for various aspects of children's cognitive and social development, most notably for the acquisition of language and for theory of mind. Differences in the quality and quantity of parental investment affect children's development and influence their subsequent reproductive and childcare strategies. Some sex differences observed in childhood, particularly as expressed during play, are seen as antecedents and preparations for adult sex differences. Because evolved mechanisms were adaptive to ancestral environments, they are not always adaptive for contemporary people, and this mismatch of evolved mechanisms with modern environments is seen in children's maladjustment to some aspects of formal schooling. We argue that an evolutionary perspective can be valuable for developing a better understanding of human ontogeny in contemporary society and that a developmental perspective is important for a better understanding of evolutionary psychology.


Reference database of CrossLaps and osteocalcin for a healthy Iranian population.
Markers of bone turnover are becoming an important tool for practitioners in the management of osteoporosis. Therefore, it is essential to establish a reference database of the markers before using them in various clinical settings. A total of 785 individuals (37% males, 63% females) without apparent or suggested abnormalities affecting bone mass were randomly selected from 13 clusters in Bushehr Port in southern Iran. The serum CrossLaps ELISA and the N-MID Osteocalcin ELISA were used for the quantitative measurement of CrossLaps and osteocalcin in sera. Bone mineral density was determined for the lumbar spines (L2-L4), proximal femur (neck), and forearm (the distal part) using dual-energy X-ray absorptiometry. Men had higher biochemical serum bone markers (P<0.0001). In women, there were progressive increases in serum CrossLaps after 30 years of age, peaking at >60 years. In men, serum CrossLaps levels were decreased progressively by increases in age, with the peak at 20 - 29 years. In women, there was a significant decrease in serum osteocalcin from 20 - 29 years to 30-49 years, followed by a progressive increases during 50 - 59 years, with the peak at >60 years. In men, the highest concentrations for serum osteocalcin occurred at 20 - 29 years. At all sites checked for bone mineral densitys, women in the high osteocalcin quartile had the lowest mean bone mineral densitys values, but women in the high CrossLaps quartile had the lowest mean bone mineral densitys at lumbar and radial sites. However, in men, bone mineral densitys values at neither site differed between the lowest and the highest quartiles of serum biochemical bone markers. We presented a five- year age-specific mean values of bone markers in a general healthy Iranian population. Only women in the high osteocalcin and CrossLaps quartiles had the lowest mean bone mineral densitys values at the lumbar and radial sites. Our results suggest that the significance of osteoclastic bone resorption or bone formation as a determinant of bone mineral densitys may depend on sex.


Clinically applicable delineation of the pallidal sensorimotor region in patients with advanced Parkinson's disease: study of probabilistic and deterministic tractography.
OBJECTIVEDeep brain stimulation (DBS) is an effective procedure in improving motor symptoms for patients with advanced Parkinson's disease (PD) through the use of high-frequency stimulation. Although one of the most commonly used target sites for DBS, sensorimotor regions of the globus pallidus interna (GPi) have yet to be thoroughly described with advanced neuroimaging analysis in vivo for human subjects. Furthermore, many imaging studies to date have been performed in a research setting and bring into question the feasibility of their applications in a clinical setting, such as for surgical planning. This study compares two different tractography methods applied to clinically feasible acquisition sequences in identifying sensorimotor regions of the GPi and the subthalamic nucleus (STN) in patients with advanced PD selected to undergo DBS.METHODSSeven patients with refractory PD selected for DBS were examined by MRI. Diffusion images were acquired with an average acquisition time of 15 minutes. Probabilistic and deterministic tractography methods were applied to each diffusion-weighted data set using FSL and MRtrix, respectively. Fiber assignment was performed using combined sensorimotor areas as initiation seeds and the STN and GPi, separately, as inclusion masks. Corticospinal tracts were excluded by setting the cerebral peduncles as exclusion masks. Variability between proposed techniques was shown using center of gravity (CoG) coordinates.RESULTSDeterministic and probabilistic corticopallidal and corticosubthalamic pathways were successfully reconstructed for all subjects across all target sites (bilaterally). Both techniques displayed large connections between the sensorimotor cortex with the posterolateral aspect of the ipsilateral GPi and the posterosuperolateral aspect of the ipsilateral STN. The average variability was 2.67 mm, with the probabilistic method identifying the CoG consistently more posterior and more lateral than the deterministic method.CONCLUSIONSSuccessful delineation of the sensorimotor regions in both the GPi and STN is achievable within a clinically reasonable timeframe. The techniques described in this paper may enhance presurgical planning with increased accuracy and improvement of patient outcomes in patients undergoing DBS. The variability found between tracking techniques warrants the use of the probabilistic tractography method over the deterministic method for presurgical planning. Probabilistic tractography was found to have an advantage over deterministic tractography in its sensitivity, in accurately describing previously described tracts, and in its ability to detect a larger number of fibers.


Leishmaniasis.
Leishmaniasis is a poverty-related disease with two main clinical forms: visceral leishmaniasis and cutaneous leishmaniasis. An estimated 0·7-1 million new cases of leishmaniasis per year are reported from nearly 100 endemic countries. The number of reported visceral leishmaniasis cases has decreased substantially in the past decade as a result of better access to diagnosis and treatment and more intense vector control within an elimination initiative in Asia, although natural cycles in transmission intensity might play a role. In east Africa however, the case numbers of this fatal disease continue to be sustained. Increased conflict in endemic areas of cutaneous leishmaniasis and forced displacement has resulted in a surge in these endemic areas as well as clinics across the world. WHO lists leishmaniasis as one of the neglected tropical diseases for which the development of new treatments is a priority. Major evidence gaps remain, and new tools are needed before leishmaniasis can be definitively controlled.


Control of endemic nosocomial legionnaires' disease by using sterile potable water for high risk patients.
In a setting where potable water is contaminated with Legionella pneumophila serogroup 1, we performed two case control studies. The first case control study consisted of 17 cases of nosocomial Legionnaires' disease (LD) and 33 control (the patients who were admitted to the ward where the case was admitted immediately before and after the case) subjects. Cases had a higher mortality rate 65% vs 12% (P less than 0.004); were more likely to have received assisted ventilation (P less than 0.00001); to have nasogastric tubes (P less than 0.0004) and to be receiving corticosteroids or other immunosuppressive therapy (P less than 0.0001). Based on the results of this study, sterile water was used to flush nasogastric tubes and to dilute nasogastric feeds. Only 3 cases of nosocomial LD occurred during the next year compared with 12 the previous year (P less than 0.0001). Nine cases subsequently occurred and formed the basis for the second case-control study. Eighteen control subjects were those patients admitted to the same unit where the case developed LD, immediately before and after the case. The mortality rate for the cases was 89% vs 6% for controls (P less than 0.00003). The only other significant difference was that cases were more likely to be receiving corticosteroids or other immunosuppressive therapy 89% vs 39% (less than 0.01). We hypothesized that microaspiration of contaminated potable water by immunocompromised patients was a risk factor for nosocomial Legionnaires' disease. From 17 March 1989 onwards such patients were given only sterile potable water. Only two cases of nosocomial LD occurred from June 1989 to September 1990 and both occurred on units where the sterile water policy was not in effect. We conclude that aspiration of contaminated potable water is a possible route for acquisition of nosocomial LD in our hospital and that provision of sterile potable water to high risk patients (those who are receiving corticosteroids or other immunosuppressive drugs; organ transplant recipients or hospitalized in an intensive care unit) should be mandatory.


Palliative care in cervical cancer.
1. Cervical cancer is the most frequent cancer in females and also the most frequent among female genital cancers. 2. Ever though the modality of diagnostic procedures for early detection has improved, in fact most of the patients present in the late stages, so the disease is already incurable, and palliative care is really needed. 3. Palliative care is needed not only for the terminally ill patients, but can be started at the time the cancer is diagnosed. 4. Palliative care is a multidisciplinary approach requiring teamwork. 5. Palliative care in Indonesia, especially in Dr. Soetomo Hospital, is a new modality in the fight against cancer, so we suffer many disadvantages, e.g., disability, limitation, lack of experience. However, such problems will stimulate the team to learn more.


Comparison of ketamine-induced thought disorder in healthy volunteers and thought disorder in schizophrenia.
This study sought to determine whether thought disorder induced in healthy volunteers by the N-methyl-D-aspartic acid (NMDA) receptor antagonist ketamine resembles the thought disorder found in patients with schizophrenia. The Scale for the Assessment of Thought, Language, and Communication was used to assess thought disorder in healthy volunteers (N = 10) who received subanesthetic doses of ketamine and in a group of clinically stable inpatients with schizophrenia (N = 15) who did not receive ketamine. Mean scores on the Scale for the Assessment of Thought, Language, and Communication for patients with schizophrenia and healthy volunteers receiving ketamine did not differ significantly. Moreover, three of the four highest rated test items in both groups were the same. These data suggest that ketamine-induced thought disorder in healthy volunteers is not dissimilar to the thought disorder in patients with schizophrenia and provide support for the involvement of the NMDA receptor in a cardinal symptom of schizophrenia.


[Advances of transgenic breeding in livestock].
Transgenic technology represents a revolutionary way to produce elite livestock breeds, allowing introduction of alien gene into livestock genome. Currently, pronuclear microinjection of DNA and somatic cell nuclear transfer are two popular methods used to make transgenic farm animals. Transgenic technology can be used in livestock breeding for improving disease resistance, carcass composition, lactational performance, wool production, growth rate, and reproductive performance, as well as reducing negative environmental impact. In addition to introduction of animal transgenic technologies, this review described the status and the future perspective of transgenic breeding in livestock.


Maternal uniparental disomy for chromosome 14.
We report the first case of maternal uniparental disomy of chromosome 14 in humans. The male proband inherited a balanced 13;14 Robertsonian translocation from his mother. Molecular studies showed that neither chromosome 14 was of paternal origin. The proband is of above average intelligence, but he has hydrocephalus, a bifid uvula, premature puberty, short stature, and small testes. It is not known if the clinical findings are related or coincidental to the uniparental disomy.


Sequelae of the initial attack of acute rheumatic fever in children from north India. A prospective 5-year follow-up study.
We determined the outcome of acute rheumatic fever in 85 children from North India who had received regular antistreptococcal prophylaxis after their first attack. By the end of the 5-year follow-up, 33 patients had rheumatic heart disease. Mitral insufficiency, the most common valvular lesion, appeared in 91% of the patients, whereas mitral stenosis developed in only 18%. Initial carditis, congestive heart failure, cardiomegaly or moderate-to-severe mitral insufficiency significantly increased the risk of rheumatic heart disease (p less than 0.001). The recurrence rate of acute rheumatic fever in children who received continuous prophylaxis was 0.006 per patient-year. Most recurrence (92%) mimicked the first attack and produced further cardiac damage in five patients with carditis and in one patient with chorea. Cardiac status during the first attack of rheumatic fever and the continuity of prophylaxis were the major determinants of outcome. Statistical comparisons disclosed that with continuous prophylaxis, the prevalence rate, evolution and clinical spectrum of the sequelae of acute rheumatic fever in children from India do not differ significantly from those in the West.


The strategies to DVI challenges in Typhoon Morakot.
Small village populations in which there is a high amount of kinship can cause complications in cases of disaster victim identification. This problem was highlighted by the loss of life after Typhoon Morakot struck Taiwan where over 500 people from small isolated communities lost their lives. Most of the victims were buried by landslides in the remote mountainous areas of southern Taiwan. Only 146 pieces of human remains were recovered after searching for 4 months. Most of the human remains were received for examination as severely damaged fragments prevented possible identification by morphological features. DNA testing using the traditional duo parent/child or sibling screening by STR data opens the possibility of including not only the actual victim but also false positives. Variable likelihood ratios were obtained when comparing DNA types from human remains to those from potential relatives; however, with the DNA typing of numerous members of the same living family, multiple matches to potential families were avoided. Of the 146 samples obtained and collapsed to 130 victims, they were linked to 124 individuals resulting in their identification when compared to a pool of 588 potential relatives. Six of the human remains could not be linked to any living relative and remain unknown.


Regulated hypothermia in the hypothyroid rat induced by administration of propylthiouracil.
Propylthiouracil (PTU), an antithyroidal drug that reduces serum L-thyroxine (T4) and 3,5,3'-triiodothyronine (T3), is presumed to lower core temperature (T0) by impairing metabolic thermogenesis. However, it is not understood why PTU-treated animals cannot use behavioral and other thermoeffectors to maintain normal Tc. Male rats were administered PTU in drinking water (0.05 mg/ml) while the following parameters were measured: 1) Tc and motor activity (MA) recorded by radiotelemetry for 24 h at ambient temperatures (Ta) of 10-30 degrees C; 2) selected Ta, MA, and Tc in a temperature gradient; and 3) Tc, MA, and grooming behavior during exposure to heat stress (TH = 34.5 degrees C) for 2 h. PTU reduced serum levels of T4, and T3 by 95 and 60%, respectively. Tc decreased after 3 days of PTU treatment; a 0.5 degree C decrease in Tc persisted throughout the PTU treatment. PTU rats exposed to Ta of 10-30 degrees C maintained a consistent hypothermic Tc during the light phase; however, a deficit in the stability of Tc at night was noted during exposure to 10 degrees C. In the temperature gradient, PTU rats selected warmer Ta, but their Tc was maintained at the same hypothermic levels as observed at fixed Ta values of 15-30 degrees C. Heat stress caused Tc of control rats to increase to 39 degrees C, whereas Tc of the PTU rats was maintained below 38 degrees C. The regulation of Tc at hypothermic levels over a wide range of Ta values and when rats were housed in a temperature gradient indicates that chronic PTU induces a state of regulated hypothermia.


The effects of Th17 cytokines on the inflammatory mediator production and barrier function of ARPE-19 cells.
Th17 cells have emerged as a key factor in the pathogenesis of uveitis as well as other autoimmune disorders. They secrete a number of cytokines including IL-17A, IL-17F and IL-22 and until now the effects of these cytokines on resident cells of the eye were not yet clear. The purpose of this study was to investigate the effects of Interleukin (IL)-17A, IL-17F and IL-22 on the production of inflammatory mediators and barrier function of retinal pigment epithelium cells. We showed that ARPE-19 cells, a spontaneously arisen cell line of retinal pigment epithelium (RPE), constitutively expressed IL-17RC and IL-22R, but not IL-17RA. IL-17A significantly enhanced the production of CXCL8, CCL2, CCL20 and IL-6 by these cells. IL-17F had a similar effect on the production of CXCL8, CCL2 and IL-6 by ARPE-19 cells, but did not influence the expression of CCL20. Both IL-17A and IL-17F significantly decreased the transepithelial electrical resistance (TER) of the ARPE-19 monolayer and increased the diffusion rate of fluorescein isothiocyanate (FITC)-dextran. They also disrupted the distribution of the junction proteins zonula occludens (ZO)-1 and occludin at the interface of adjacent cells. IL-22 did not have a detectable effect on the production of the tested inflammatory mediators by ARPE-19 cells, TER of the ARPE-19 monolayer, the diffusion rate of FITC-dextran or the distribution of ZO-1 and occludin. This study demonstrates that IL-17A and IL-17F, but not IL-22, significantly promoted ARPE-19 cells to secrete inflammatory mediators and compromised the ARPE-19 monolayer barrier function in association with a disrupted distribution of ZO-1 and occludin. These results suggest that both IL-17A and IL-17F may play a role in posterior segment inflammation of the eye.