Genetic diversity and population structure of a rare flowering tree endemic to Appalachia, Stewartia ovata.

Stewartia ovata (cav.) Weatherby, commonly known as mountain stewartia, is an understory tree native to the southeastern United States (U.S.). This relatively rare species occurs in isolated populations in Virginia, Kentucky, Tennessee, North Carolina, South Carolina, Georgia, Alabama, and Mississippi. As a species, S. ovata has largely been overlooked, and limited information is available regarding its ecology, which presents obstacles to conservation efforts. Stewartia ovata has vibrant, large white flowers that bloom in summer with a variety of filament colors, suggesting potential horticultural traits prized by ornamental industry. However, S. ovata is relatively slow growing and, due to long seed dormancy, propagation is challenging with limited success rates. This has created a need to assess the present genetic diversity in S. ovata populations to inform potential conservation and restoration of the species. Here, we employ a genotyping-by-sequencing (GBS) approach to characterize the spatial distribution and genetic diversity of S. ovata in the southern Appalachia region of the eastern United States. A total of 4475 single nucleotide polymorphisms (SNPs) were identified across 147 individuals from 11 collection sites. Our results indicate low genetic diversity (He = 0.216), the presence of population structure (K = 2), limited differentiation (F ST = 0.039), and high gene flow (Nm = 6.16) between our subpopulations. Principal component analysis corroborated the findings of STRUCTURE, confirming the presence of two distinct S. ovata subpopulations. One subpopulation mainly contains genotypes from the Cumberland Plateau, Tennessee, while the other consists of genotypes present in the Great Smoky Mountain ranges in Tennessee, North Carolina, and portions of Nantahala, Chattahoochee-Oconee national forests in Georgia, highlighting that elevation likely plays a major role in its distribution. Our results further suggested low inbreeding coefficient (F IS = 0.070), which is expected with an outcrossing tree species. This research further provides necessary insight into extant subpopulations and has generated valuable resources needed for conservation efforts of S. ovata.

Deletion of voltage-gated calcium channels in astrocytes decreases neuroinflammation and demyelination in a murine model of multiple sclerosis.

The experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis was used in combination with a Cav1.2 conditional knock-out mouse (Cav1.2KO) to study the role of astrocytic voltage-gated Ca++ channels in autoimmune CNS inflammation and demyelination. Cav1.2 channels were specifically ablated in Glast-1-positive astrocytes by means of the Cre-lox system before EAE induction. After immunization, motor activity was assessed daily, and a clinical score was given based on the severity of EAE symptoms. Cav1.2 deletion in astrocytes significantly reduced the severity of the disease. While no changes were found in the day of onset and peak disease severity, EAE mean clinical score was lower in Cav1.2KO animals during the chronic phase of the disease. This corresponded to better performance on the rotarod and increased motor activity in Cav1.2KO mice. Furthermore, decreased numbers of reactive astrocytes, activated microglia, and infiltrating lymphocytes were found in the lumbar section of the spinal cord of Cav1.2KO mice 40 days after immunization. The degree of myelin protein loss and size of demyelinated lesions were also attenuated in Cav1.2KO spinal cords. Similar results were found in EAE animals treated with nimodipine, a Cav1.2 Ca++ channel inhibitor with high affinity to the CNS. Mice injected with nimodipine during the acute and chronic phases of the disease exhibited lower numbers of reactive astrocytes, activated microglial, and infiltrating immune cells, as well as fewer demyelinated lesions in the spinal cord. These changes were correlated with improved clinical scores and motor performance. In summary, these data suggest that antagonizing Cav1.2 channels in astrocytes during EAE alleviates neuroinflammation and protects the spinal cord from autoimmune demyelination.

The expression of ceruloplasmin in astrocytes is essential for postnatal myelination and myelin maintenance in the adult brain.

Ceruloplasmin (Cp) is a ferroxidase enzyme that is essential for cell iron efflux. The absence of this protein in humans and rodents produces progressive neurodegeneration with brain iron accumulation. Astrocytes express high levels of Cp and iron efflux from these cells has been shown to be central for oligodendrocyte maturation and myelination. To explore the role of astrocytic Cp in brain development and aging we generated a specific conditional KO mouse for Cp in astrocytes (Cp cKO). Deletion of Cp in astrocytes during the first postnatal week induced hypomyelination and a significant delay in oligodendrocyte maturation. This abnormal myelin synthesis was exacerbated throughout the first two postnatal months and accompanied by a reduction in oligodendrocyte iron content, as well as an increase in brain oxidative stress. In contrast to young animals, deletion of astrocytic Cp at 8 months of age engendered iron accumulation in several brain areas and neurodegeneration in cortical regions. Aged Cp cKO mice also showed myelin loss and oxidative stress in oligodendrocytes and neurons, and at 18 months of age, developed abnormal behavioral profiles, including deficits in locomotion and short-term memory. In summary, our results demonstrate that iron efflux-mediated by astrocytic Cp-is essential for both early oligodendrocyte maturation and myelin integrity in the mature brain. Additionally, our data suggest that astrocytic Cp activity is central to prevent iron accumulation and iron-induced oxidative stress in the aging CNS.

Enhancing the Measure of Participation Burden in Protocol Design to Incorporate Logistics, Lifestyle, and Demographic Characteristics.

BACKGROUND: Growing interest in improving patient participation convenience and the feasible execution of clinical trials has increased demand for new approaches to leverage patient input in the protocol design process. METHODS: This study builds on prior work conducted by the Tufts Center for the Study of Drug Development in collaboration with ZS. A comprehensive participant burden algorithm based on protocol procedures, participation requirements and lifestyle preferences was developed and tested. Clinical trial preferences and perceptions from 3002 global patients were analyzed to inform and derive the algorithm. It was next tested against a convenience sample of 266 completed protocols. Descriptive statistics, significance tests, and regression analyses were performed. RESULTS: Mean participant burden scores were highly associated with, and predictive (p < 0.01) of, screen failure rates, overall clinical trial duration and the number of substantial protocol amendments; and predictive (p < 0.05) of protocol treatment duration. Of 11 subgroups assessed, those that most influenced the algorithm and drove higher overall burden scores included disease condition, caregiver reliance, race, prior experience as a clinical trial participant and participant age. Geographic area and participant sex showed only minimal influence. CONCLUSION: This study presents advancement and refinement in measuring participation burden that will assist drug development teams and protocol authors in retrospectively understanding clinical trial performance outcomes and in prospectively informing protocol design decisions.

Cross-sectional prevalence of SARS-CoV-2 antibodies in healthcare workers in paediatric facilities in eight countries.

BACKGROUND: Healthcare workers (HCWs) have been disproportionately affected by coronavirus disease 2019 (COVID-19), which may be driven, in part, by nosocomial exposure. If HCW exposure is predominantly nosocomial, HCWs in paediatric facilities, where few patients are admitted with COVID-19, may lack antibodies to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and be at increased risk during the current resurgence. AIM: To compare the seroprevalence of SARS-CoV-2 amongst HCWs in paediatric facilities in seven European countries and South Africa (N=8). METHODS: All categories of paediatric HCWs were invited to participate in the study, irrespective of previous symptoms. A single blood sample was taken and data about previous symptoms were documented. Serum was shipped to a central laboratory in London where SARS-CoV-2 immunoglobulin G was measured. FINDINGS: In total, 4114 HCWs were recruited between 1st May and mid-July 2020. The range of seroprevalence was 0-16.93%. The highest seroprevalence was found in London (16.93%), followed by Cape Town, South Africa (10.36%). There were no positive HCWs in the Austrian, Estonian and Latvian cohorts; 2/300 [0.66%, 95% confidence interval (CI) 0.18-2.4] HCWs tested positive in Lithuania; 1/124 (0.81%, 95% CI 0.14-4.3) HCWs tested positive in Romania; and 1/76 (1.3%, 95% CI 0.23-7.0) HCWs tested positive in Greece. CONCLUSION: Overall seroprevalence amongst paediatric HCWs is similar to their national populations and linked to the national COVID-19 burden. Staff working in paediatric facilities in low-burden countries have very low seroprevalence rates and thus are likely to be susceptible to COVID-19. Their susceptibility to infection may affect their ability to provide care in the face of increasing cases of COVID-19, and this highlights the need for appropriate preventative strategies in paediatric healthcare settings.

Simultaneous recovery of both bright and dim structures from noisy fluorescence microscopy images using a modified TV constraint.

The quality and information content of biological images can be significantly enhanced by postacquisition processing using deconvolution and denoising. However, when imaging complex biological samples, such as neurons, stained with fluorescence labels, the signal level of different structures can differ by several orders of magnitude. This poses a challenge as current image reconstruction algorithms are focused on recovering low signals and generally have sample-dependent performance, requiring tedious manual tuning. This is one of the main hurdles for their wide adoption by nonspecialists. In this work, we modify the general constrained reconstruction method (in our case utilizing a total variation constraint) so that both bright and dim structures can drive the deconvolution with equal force. In this way, we can simultaneously obtain high-quality reconstruction across a wide range of signals within a single image or image sequence. The algorithm is tested on both simulated and experimental data. When compared with current state-of-art algorithms, our algorithm outperforms others in terms of maintaining the resolution in the high-signal areas and reducing artefacts in the low-signal areas. The algorithm was also tested on image sequences where one set of parameters are used to reconstruct all images, with blind evaluation by a group of biologists demonstrating a marked preference for the images produced by our method. This means that our method is suitable for batch processing of image sequences obtained from either spatial or temporal scanning. LAY DESCRIPTION: Fluorescence microscopy images of complex biological samples contain a wide range of signal levels. This signal variation leads current reconstruction algorithms, which aim to enhance the quality of the raw images, to have sample-dependent performance. In this work, we design a new optimization that allows the reconstruction to "pay equal eqattention to" both bright and dim structures. In this way, we can simultaneously recover both bright and dim structures within a single image or image sequence, as validated when the algorithm was quantitatively tested on both simulated and experimental data. When our method was evaluated alongside current state of art algorithms by a group of biologists, our algorithm was considered qualitatively superior.

Anabolic payout of terminal implant alters adipogenic gene expression of the longissimus muscle in beef steers.

This experiment evaluated the dose and payout pattern of trenbolone acetate (TBA) and estradiol-17ß (E) on LM mRNA expression of adenosine monophosphate-activated protein kinase-ɑ (-ɑ), ß, G protein-coupled receptor 41(), G protein-coupled receptor 43 (), γ, and stearoyl CoA desaturase () in finishing feedlot steers as indicators of adipogenesis and marbling development. British × Continental steers (n = 168; 14 pens/treatment; initial BW = 362 kg) were used in a randomized complete block design. Treatments included: no implant (NI), Revalor-S (REV-S; 120 mg TBA + 24 mg E), or Revalor-XS (REV-X; delayed release implant: 80 mg TBA + 16 mg E [uncoated], 120 mg TBA + 24 mg E [coated], 200 mg TBA + 40 mg E [total]). Steers were fed 1 time daily for an average of 164 d. The LM biopsies were collected (1 steer/pen) on d -1, 27, 55, and 111 relative to timing of implant. Total RNA was isolated from each sample and real-time quantitative PCR was used to measure quantity of -ɑ, ß, , ,it, γ, and mRNA. No implant × day interactions were detected ( ≥ 0.19) in this experiment. Day impacted the mRNA expression of all adipogenic genes ( ≤ 0.02). The main effect of implant tended ( = 0.09) to influence expression of -ɑ, REV-X had an 8.8% increase over NI and an 18.7% increase over REV-S. Implant influenced ( = 0.03) mRNA expression of , expression of for the REV-X treatment was not different ( > 0.10) from NI, and both were greater ( ≤ 0.05) than REV-S (1.13, 1.00, and 0.67 ± 0.224 arbitrary units) for REV-X, NI, and REV-S, respectively. Implant also influenced ( = 0.02) expression of , expression of for REV-X was not different ( > 0.10) from NI, and both were greater ( ≤ 0.05) than REV-S (1.27, 1.07, and 0.72 ± 0.234 arbitrary units) for REV-X, NI, and REV-S, respectively. Implant influenced ( = 0.02) mRNA expression of γ in LM tissue, expression of γ for REV-X was not different ( > 0.10) from NI, and both were greater ( ≤ 0.05) than REV-S (1.09, 1.02, and 0.69 ± 0.195 arbitrary units) for REV-X, NI, and REV-S, respectively. The REV-X steers received the greatest anabolic dose of TBA + E without detriment to marbling scores. The increased mRNA expression of adipogenic genes for REV-X steers suggest that the delayed and gradual release of anabolic stimulants associated with REV-X might have mitigated decreases in marbling generally attributed to multiple combined TBA + E implants.

Ionophore strategy affects growth performance and carcass characteristics in feedlot steers.

One hundred ninety-two steers (BW = 354 ± 23.5 kg) were used in a randomized block design to evaluate the effects of ionophore and ractopamine hydrochloride (RH) supplementation strategies on performance and carcass characteristics. Twelve pens of 4 steers were assigned to each of the following treatments: unsupplemented control (CON), laidlomycin propionate (12.1 mg/kg DM) with or without RH (LPRH and LP, respectively), and monensin sodium (36.4 mg/kg DM) with RH (MSRH). Steers were fed for 151 d, of which respective treatments received RH (Actogain; Zoetis, Florham Park, NJ) at a rate of 300 mg/(animal · d) for the final 32 d. Laidlomycin was removed from the LPRH treatment during this period, as no combination feeding has been approved. Upon harvest, carcass data were collected by trained personnel, and subsequent analysis of the LM was conducted to estimate tenderness using Warner-Bratzler shear force (WBSF). Prior to RH supplementation, both LP and LPRH had greater ADG ( ≤ 0.02) and G:F ( < 0.01) than CON, whereas MSRH was intermediate. During the final 32 d, MSRH improved G:F ( ≤ 0.02) compared to all other treatments and tended to increase ADG over unsupplemented controls ( = 0.05). Cattle receiving LP without RH had significantly greater BW at d 151 than CON ( = 0.02), whereas both RH treatments tended to improve final BW ( ≤ 0.09). Ionophores improved ADG ( ≤ 0.03) and G:F ( < 0.01) for the entire feeding period, and although LP-supplemented cattle had greater DMI for the final 32 d than both RH treatments ( ≤ 0.01), intakes for the 151-d trial were similar among treatments. Carcass weights were greater ( = 0.04) in cattle fed LP with no RH than CON, where cattle yielded an average of 12 kg more HCW. Ractopamine increased LM area in MSRH-supplemented cattle ( = 0.03) and tended to increase LM area for steers receiving LPRH ( = 0.07). Longissimus steaks of MSRH-supplemented cattle had greater WBSF values than CON ( = 0.04) after 7 d of postmortem aging and greater WBSF values than LPRH steaks after 28 d ( = 0.03). All other carcass and WBSF measurements were similar among treatments. The results of this study indicate that LP supplementation without RH may yield a performance similar to and carcass responses associated with the administration of a ß-agonist. These results also suggest that performance and carcass characteristics for cattle fed LP are similar to those of cattle fed monensin throughout the feeding period.

Epidemiology and factors associated with candidaemia following Clostridium difficile infection in adults within metropolitan Atlanta, 2009-2013.

We assessed prevalence of and risk factors for candidaemia following Clostridium difficile infection (CDI) using longitudinal population-based surveillance. Of 13 615 adults with CDI, 113 (0·8%) developed candidaemia in the 120 days following CDI. In a matched case-control analysis, severe CDI and CDI treatment with vancomycin + metronidazole were associated with development of candidaemia following CDI.

The medico-legal investigation of abandoned fetuses and newborns--a review of cases admitted to the Pretoria Medico-Legal Laboratory, South Africa.

There is a dearth of literature on the extent of fetal or newborn abandonment or "dumping" and the medico-legal investigation procedures these cases require. This is despite the fact that these occurrences are a worldwide phenomenon and by definition involve criminal law concerns such as illegal abortion, concealment of birth, murder, or neonaticide, depending on the country concerned. This article contributes to current literature in both respects and provides a retrospective case audit for the period 2004-2008 pertaining to all abandoned newborns and fetuses admitted to the Pretoria Medico-Legal Laboratory (PMLL) in South Africa. Demographic details, scope, and nature of the medico-legal investigation as well as formulation of cause of death were recorded. A total of 289 cases were identified for inclusion in this study, 57% of which were considered to have been non-viable fetuses, while 45 of the viable fetuses were deemed to have been stillborn. These instances involve the crimes of concealment of birth and at times illegal abortion, yet prosecution of these cases are relatively unheard of. Signs of live birth were identified in 38 of the cases in the study. Of these infants, 9 were deemed to have died from injuries they have sustained, and in a further 9 cases, no anatomical cause of death could be identified. Homicidal cases should be brought in cases where death ensued as a result of abandonment; however, it is not known how many cases were prosecuted. A comparatively large number of cases were found to have been admitted to the Pretoria Medico-Legal Laboratory. This is alarming because South African abortion laws are liberal and services are free at point of access in the public health care sector. A substantial percentage of cases of abandoned infants were found to have shown signs of life after birth implying a homicidal manner of death or death by abandonment, but it seems these cases are merely shelved.

N-Acetylcysteine improves mitochondrial function and ameliorates behavioral deficits in the R6/1 mouse model of Huntington's disease.

Huntington's disease (HD) is a neurodegenerative disorder, involving psychiatric, cognitive and motor symptoms, caused by a CAG-repeat expansion encoding an extended polyglutamine tract in the huntingtin protein. Oxidative stress and excitotoxicity have previously been implicated in the pathogenesis of HD. We hypothesized that N-acetylcysteine (NAC) may reduce both excitotoxicity and oxidative stress through its actions on glutamate reuptake and antioxidant capacity. The R6/1 transgenic mouse model of HD was used to investigate the effects of NAC on HD pathology. It was found that chronic NAC administration delayed the onset and progression of motor deficits in R6/1 mice, while having an antidepressant-like effect on both R6/1 and wild-type mice. A deficit in the astrocytic glutamate transporter protein, GLT-1, was found in R6/1 mice. However, this deficit was not ameliorated by NAC, implying that the therapeutic effect of NAC is not due to rescue of the GLT-1 deficit and associated glutamate-induced excitotoxicity. Assessment of mitochondrial function in the striatum and cortex revealed that R6/1 mice show reduced mitochondrial respiratory capacity specific to the striatum. This deficit was rescued by chronic treatment with NAC. There was a selective increase in markers of oxidative damage in mitochondria, which was rescued by NAC. In conclusion, NAC is able to delay the onset of motor deficits in the R6/1 model of Huntington's disease and it may do so by ameliorating mitochondrial dysfunction. Thus, NAC shows promise as a potential therapeutic agent in HD. Furthermore, our data suggest that NAC may also have broader antidepressant efficacy.

The regulated synthesis of a Bacillus anthracis spore coat protein that affects spore surface properties.

AIMS: Examine the regulation of a spore coat protein and the effects on spore properties. METHODS AND RESULTS: A c. 23 kDa band in coat/exosporial extracts of Bacillus anthracis Sterne spores varied in amount depending upon the conditions of sporulation. It was identified by MALDI as a likely orthologue of ExsB of Bacillus cereus. Little if any was present in an exosporial preparation with a location to the inner coat/cortex region established by spore fractionation and immunogold labelling of electron micrograph sections. Because of its predominant location in the inner coat, it has been renamed Cotγ. It was relatively deficient in spores produced at 37°C and when acidic fermentation products were produced a difference attributable to transcriptional regulation. The deficiency or absence of Cotγ resulted in a less robust exosporium positioned more closely to the coat. These spores were less hydrophobic and germinated somewhat more rapidly. Hydrophobicity and appearance were rescued in the deletion strain by introduction of the cotγ gene. CONCLUSIONS: The deficiency or lack of a protein largely found in the inner coat altered spore hydrophobicity and surface appearance. SIGNIFICANCE AND IMPACT OF THE STUDY: The regulated synthesis of Cotγ may be a paradigm for other spore coat proteins with unknown functions that modulate spore properties in response to environmental conditions.

Effects of the 5-HT2C receptor agonist meta-chlorophenylpiperazine on appetite, food intake and emotional processing in healthy volunteers.

RATIONALE: The treatment of obesity is an increasing global health priority, yet few effective drug treatments are currently available. The discovery of novel anti-obesity therapies could be assisted by the validation of experimental (translational) medicine models in healthy volunteers that assess efficacy and safety at an early stage of drug development. OBJECTIVES: The aim of this study was to examine the effects of the 5-HT2C receptor agonist meta-chlorophenylpiperazine (mCPP) in an experimental medicine model assessing both appetite and mood. METHODS: Using a between-subjects, double-blind, placebo-controlled design, 24 male and 24 female participants were randomly assigned to either placebo, 15- or 30-mg mCPP treatment groups. Lunch was eaten from a Universal Eating Monitor (UEM) that measured eating rate, and the participants completed the P1vital® Oxford Emotional Test Battery (ETB) and a series of appetite and mood ratings. RESULTS: mCPP reduced appetite and, in women, enhanced measures of satiation. The drug also enhanced memory for emotional material in the word recall and recognition memory tasks of the ETB. CONCLUSIONS: The results provide new insight into the effects of mCPP on appetite, satiety and memory in humans. In addition, our data provide an illustration of the value of measuring changes in appetite and mood in healthy volunteers to determine the potential efficacy and safety of novel anti-obesity drugs.

Complete absence of the posterior arch of C1: Case report.

Posterior atlas arch anomalies are relatively common, but have a variety of presentations ranging from partial clefts to complete agenesis of the posterior arch. Partial clefts are prevalent in 4% of patients and are generally asymptomatic. However, complete agenesis of the posterior arch is extremely rare. We report the case of a 46-year-old man who presented with upper cervical spine and occipital pain as well as left sided headaches. Imaging revealed congenital complete absence of the posterior arch of C1 (Type E) without any radiographic evidence of instability. We discuss our case in light of other reported cases and detail its management.

In vitro biomechanical comparison of load to failure testing of a canine unconstrained medial compartment elbow arthroplasty system and normal canine thoracic limbs.

Elbow dysplasia, primarily affecting the medial compartment, is the most common cause of lameness in the thoracic limb. Elbow arthroplasty is an option for end stage or severely affected patients. The purpose of this study was to compare ex vivo axial load to failure of an implanted novel elbow arthroplasty system to control limbs. The partial arthroplasty is a medial compartmental, unconstrained system, intended to allow conversion to total arthroplasty. We hypothesized that there would not be any significant difference between implanted and controlled limbs when loaded to failure. Six pairs of medium mixed breed canine cadaveric thoracic limbs were prepared for comparison of failure loading of control and implanted limbs. Axial compression was performed using a mechanical testing system. Failure loads were normalized to bodyweight. The mean normalized failure load (N/kg) for the implanted limbs and control limbs were 2.47 (range: 1.62-3.38) and 2.68 (range: 2.25-3.25), respectively. An implanted to control ratio of 0.93 ± 0.19 was calculated. The difference between paired control and implanted limbs in normalized failure loading was not significant (p = 0.38). There were not any differences noted in the yield load (p = 0.30), stiffness (p = 0.62), or energy (0.58). Failure modes were recorded. We concluded that the differences between implanted and control limbs in supra-physiologic axial load to failure were not significant.

Outcomes in critical care delivery at Jimma University Specialised Hospital, Ethiopia.

The aim of this study was to assess outcomes following intensive care unit (ICU) admissions at Jimma University Specialised Hospital, Ethiopia. This was a retrospective observational study. Data were collected regarding all ICU admissions and discharges during a 12-month period beginning August 2011. Demographic data and information regarding diagnosis, length-of-stay and outcome were gathered and data analysed. There were 370 admissions to the ICU during the study period. Median age (interquartile range) was 32.0 (22.0-47.0) years and 56.2% were males. The median length-of-stay (interquartile range) was 3.0 (1.0-7.0) days. The overall ICU mortality rate was 50.4% and major causes included trauma, cardiac disease, acute abdominal presentations, septic shock, tetanus and hysterectomy secondary to uterine rupture. Medical diagnoses accounted for 50.1% of admissions followed by surgery (43.2%) and obstetrics (5.8%). Corresponding mortality rates were 53.6, 48.0 and 42.9%, respectively. The main cause for surgical admission was trauma, with head injury carrying a mortality of 52.1%. The principal cause for medical admission was cardiac disease. In children, trauma, upper airway obstruction and communicable diseases were most common. Critical care mortality rates at this Ethiopian university hospital reflect the challenges facing critical care delivery in the developing world. Delayed presentation to hospital secondary to poor access to healthcare plays a predominant role. This is confounded by inadequate staffing, training, diagnostic and interventional limitations. Despite resource restraints, simple cost-effective measures may improve morbidity and mortality.

Glucocorticoid receptor density correlates with health risk factors and insulin resistance in Caucasian and African American subjects.

Activation of the hypothalamic-pituitary-adrenal axis leads to secretion of cortisol, which binds to peripheral glucocorticoid receptor and mediates a complex series of metabolic and immune effects. Cortisol also binds to receptors in the hypothalamus and pituitary, and inhibits further secretion of adrenocorticotropic hormone thus preventing an excessive response. Excess glucocorticoid effect is seen in Cushings disease, adrenal adenomas/carcinomas and in glucocorticoid resistance. Within such pathology there are health consequences of excessive glucocorticoid action, including obesity, hypertension, and glucose intolerance or diabetes. We hypothesized that increased glucocorticoid receptor in peripheral tissue might mediate an excess glucocorticoid effect in the absence of increased cortisol secretion. The objective of the study was to investigate the relationship between glucocorticoid receptor density in leukocytes and health risk indices relevant to obesity and diabetes in a sample of Caucasian and African American subjects. Comparison of glucocorticoid receptor concentration with subject body mass index, percentage body fat, waist circumference, insulin resistance, plasma cortisol levels, gender, and lipid profiles were conducted. Increased glucocorticoid receptor density significantly correlated with body mass index, percentage body fat, waist circumference, and insulin resistance. No significant correlation was observed for glucocorticoid receptor density with lipid profiles. Furthermore, no significant differences were observed in glucocorticoid receptor density between Caucasian and African American subjects or male and female participants. Our results show that high risk health conditions, such as obesity and type-2 diabetes, may be associated with a form of hypothalamic-pituitary-adrenal axis dysfunction, characterized by localized leukocyte glucocorticoid receptor over-expression.

Functional characterization of four metallothionein genes in Daphnia pulex exposed to environmental stressors.

We characterized the metallothionein genes (Mt1, Mt2, Mt3, and Mt4) in Daphnia pulex on both molecular and ecotoxicological level. We therefore conducted a bioinformatical analysis of the gene location and predicted protein sequence, and screened the upstream flanking region for regulatory elements. The number of these elements and their positions relative to the start codon varied strongly among the four genes and even among two gene duplicates (Mt1A and Mt1B), suggesting different roles of the four proteins in the organisms' response to stress. We subsequently conducted a chronic 16-day exposure of D. pulex to different environmental stressors (at sublethal levels causing approximately 50% reduction in reproduction). Based on prior knowledge, we exposed them to the metals Cd, Cu, and Ni, the moulting hormone hydroxyecdysone (20E), and the oxidative stressors cyanobacteria (Microcystis aeruginosa), and paraquat (Pq). We then compared mRNA expression levels of the four Mt genes under these stress conditions with control conditions in "The Chosen One" clone (TCO), for which the full genome was sequenced and annotated. All together, the mRNA expression results under the different stress regimes indicate that different Mt genes may play different and various roles in the response of D. pulex to stress and that some (but not all) of the differences among the four genes could be related to the pattern of regulatory elements in their upstream flanking region.

The surgical technique of minimally invasive transforaminal lumbar interbody fusion.

We aim to describe the minimally invasive transforaminal lumbar interbody fusion (MI-TLIF) technique. The MI-TLIF procedure was developed to achieve the same goal of neural decompression and interbody arthrodesis as the traditional, open TLIF techniques. MI-TLIF has been utilized in the treatment of an array of lumbar pathologies, while offering the advantages of reducing soft tissue trauma, decreasing postoperative pain, and reducing the rate of complication when compared to the open techniques. The surgical technique of MI-TLIF is described in a step-by-step fassion. A technical review of this novel minimally invasive procedure was performed. Additionally, data collected through our experience with this procedure is reported. Data was collected retrospectively from patients between January 2008 and December 2009 who underwent MI-TLIF. The mean preoperative VAS score was 6.12±2.02 compared to 2.11±2.69 postoperatively. The mean ODI score dropped from 38.29±13.19 preoperatively to 16.00 ±16.598 postoperatively. Eighty-four patients who underwent MI-TLIF between October 2007 and December 2010 were divided based on age (over or under 65 years) and intraoperative estimated blood loss (EBL) was compared. The mean EBL for the young age group was 93.37±102.16 mL compared to 100 ±61.24 mL for the older group. Operation times for the MI-TLIF procedure has decreased from 3-4 hours to approximately 2 hours throughout our experience with this technique. The MI-TLIF technique is a safe and effective procedure offering the advantages of less tissue damage, less blood loss, and reduced postoperative hospitalization over the open techniques.

The effectiveness of the South African Triage Score (SATS) in a rural emergency department.

BACKGROUND. The Modified Early Warning Score (MEWS) is used to monitor medical inpatients in hospitals in the developed world. The South African Triage Score (SATS) was developed from the MEWS, and its use throughout South Africa has been proposed. OBJECTIVES. We aimed to assess the effectiveness of the SATS in an emergency department (ED) in a rural setting in KwaZulu-Natal (KZN). METHODS. A prospective cross-sectional study undertaken over a 1-month period in June 2009 of patients in the ED of a government hospital in rural KZN, the referral centre for 22 peripheral hospitals. Data capture included physiological parameters, mobility and trauma scores, a list of selected clinical conditions (physician discriminator list), MEWS and SATS scores, final clinical diagnosis, and outcome in the ED (death, hospital admission or discharge). Outcome measures were under- and over-triage rates according to both systems. RESULTS. Over the study period, 589 patients were triaged and their data analysed. The MEWS under-triaged 15.1% (over-triaged 8.3%) of cases that needed admission, compared with an under-triage rate of 4.4% (over-triage rate 4.3%) when the SATS was used. CONCLUSION. Our study supports use of the SATS as a primary triage score in South African urban and rural hospitals. The SATS is superior to the MEWS as a triage scoring system in a rural hospital ED in KZN, its rates of under- and over-triage falling within the limits of the American College of Surgeons Committee on Trauma (ACSCOT) guidelines.