Contralateral effects of unilateral resistance training: a meta-analysis.
It is often claimed that strength training of one limb increases the strength of the contralateral limb, but this has not been demonstrated consistently, particularly in well-controlled studies. The aim was to quantitatively combine the results of other studies on the effects of unilateral training on contralateral strength in humans to provide an answer to this physiological question. We analyzed all randomized controlled studies of voluntary unilateral resistance training that used training intensities of at least 50% of maximal voluntary strength for a minimum of 2 wk. Studies were identified by computerized and hand searches of the literature. Data on changes in strength of contralateral and control limbs were extracted and statistically pooled in a meta-analysis. This approach allows conclusions to be based on a statistically meaningful sample size, which might be difficult to achieve in other ways. Seventeen studies met the inclusion criteria, and 13 provided enough data for statistical pooling. The contralateral effects of strength training reported in individual studies varied from -2.7 to 21.6% of initial strength. The pooled estimate of the effect of unilateral resistance training on the maximal voluntary strength of the contralateral limb was 7.8% (95% confidence interval: 4.1-11.6%). This was 35.1% (95% confidence interval: 20.9-49.3%) of the effect on the trained limb. Pooling of all available data shows that unilateral strength training produces modest increases in contralateral strength.


Increasing the holographic matched filter information capacity.
The advantage of a sampled Fourier hologram in enhancement of the number of characters included in a matched spatial filter in Vander Lugt correlator systems is shown in this paper. A sampled Fourier hologram can be easily obtained by inserting a sampling mask adjacent to the hologram during recording. When the sampling period in the recorded sampled hologram is matched to the object spectrum, according to the Whittaker-Shannon theorem, the resulting image does not suffer any loss of information content. However, the sampled hologram covers only a small part of the photographic plate, with the result that one can record many closely packed Fourier holograms on the same area of the plate and at the same working point of the H-D curve. Thus, sampling is used as a multiplexing technique. Sets of cross-correlation or autocorrelation images are generated in the output of the correlator system. The offset angle of the reference beam must be suitably selected to prevent overlapping of the sets of images.


Hepatitis C virus mediated changes in miRNA-449a modulates inflammatory biomarker YKL40 through components of the NOTCH signaling pathway.
Liver disease due to hepatitis C virus (HCV) infection is an important health problem worldwide. HCV induced changes in microRNAs (miRNA) are shown to mediate inflammation leading to liver fibrosis. Gene expression analyses identified dysregulation of miRNA-449a in HCV patients but not in alcoholic and non-alcoholic liver diseases. By sequence analysis of the promoter for YKL40, an inflammatory marker upregulated in patients with chronic liver diseases with fibrosis, adjacent binding sites for nuclear factor of Kappa B/P65 and CCAAT/enhancer-binding protein alpha (CEBPα) were identified. P65 interacted with CEBPα to co-operatively activate YKL40 expression through sequence specific DNA binding. In vitro analysis demonstrated that tumor necrosis factor alpha (TNFα) mediated YKL40 expression is regulated by miRNA-449a and its target NOTCH1 in human hepatocytes.NOTCH1 facilitated nuclear localization of P65 in response to TNFα. Further, HCV patients demonstrated upregulation of NOTCH1 along with downregulation of miRNA-449a. Taken together it is demonstrated that miRNA-449a plays an important role in modulating expression of YKL40 through targeting the components of the NOTCH signaling pathway following HCV infection. Therefore, defining transcriptional regulatory mechanisms which control inflammatory responses and fibrosis will be important towards developing strategies to prevent hepatic fibrosis especially following HCV recurrence in liver transplant recipients.


Single-molecule torsional pendulum.
We have built a torsional pendulum based on an individual single-walled carbon nanotube, which is used as a torsional spring and mechanical support for the moving part. The moving part can be rotated by an electric field, resulting in large but fully elastic torsional deformations of the nanotube. As a result of the extremely small restoring force associated with the torsional deformation of a single molecule, unusually large oscillations are excited by the thermal energy of the pendulum. By diffraction analysis, we are able to determine the handedness of the molecule in our device. Mechanical devices with molecular-scale components are potential building blocks for nanoelectromechanical systems and may also serve as sensors or actuators.


Determinants of maternal knowledge on neonatal danger signs and care-seeking practices in a rural area of southeastern Ethiopia.
Most infants in southeastern Ethiopia are either born at home or discharged from the health facility early and families should be able to recognize signs of newborn illnesses and bring the sick newborn to a health facility to receive care. However, studies are limited and the available studies were conducted in urban areas and/or at an institution level. This study aimed to assess the determinants of maternal knowledge of neonatal danger signs and care-seeking practices. A community-based cross-sectional study was conducted on 520 post-natal mothers using a multistage sampling method from 1 to 30 March 2019. The data were analysed using SPSS version 20 using binary logistic regression. Statistical significance was declared at p<0.05. Mothers' level of knowledge of neonatal danger signs was 50.2% (95% confidence interval [CI] 46.3 to 54.3) and 61% of them sought healthcare when they noticed danger signs. Maternal education level (adjusted odds ratio [AOR] 2.15 [95% CI 1.11 to 4.17]), husband's education level (AOR 2.05 [95% CI 1.07 to 3.94]), residency (AOR 5.83 [95% CI 2.77 to 12.24]), antenatal visits (AOR 2.10 [95% CI 1.13 to 3.90]), antenatal care (ANC) counselling (AOR 4.33 [95% CI 1.88 to 9.98]) and knowledge about essential newborn care (AOR 3.91 [95% CI 2.05 to 7.48]) were the determining factors. The mothers' level of knowledge of neonatal danger signs was low and unsafe care-seeking practices were identified. The mothers' education level, husbands' education level, residence, ANC visits, counselling during ANC and knowledge about essential newborn care were found to be statistically significant determinants. Most of the mothers take their sick neonates to traditional healers and provide home remedies. Intervention modalities focusing on maternal counselling on the most common symptoms of illness in neonates are essential to increase mothers' recognition of illness and improve care-seeking practices.


Impact of stereopsis on quality of life.
To investigate the impact of stereopsis on vision-related quality of life and general health status of the elderly. A quota of 200 subjects aged 65 years or older and had their households registered in Guando district was recruited for a general physical examination including ophthalmic evaluation. A structured questionnaire consisting of seven vision-specific items as well as 36-item short-form survey of the Medical Outcomes Study (SF-36) was administered. Stereoscopic level was divided into three groups: no stereopsis, gross stereopsis, and fine stereopsis. Fisher's exact test was used to detect any difference in subjective visual functioning and Mann-Whitney U test was used for analyses of SF-36 scores. A total of 187 volunteers were recruited and 150 were analysed for stereoscopic levels. There was no significant difference in vision-specific difficulty among the three stereoscopic groups. For SF-36, having no stereopsis scored significantly less than having gross (P=0.005) and fine (P<0.0001) stereopsis in the vitality/energy dimension. General health perception dimension fared significantly lower in the group with no stereopsis compared to the fine stereoscopic group (P=0.01). In multivariate analysis, having fine stereopsis scored significantly higher in the energy/vitality dimension than having no stereopsis (P=0.02). On the other hand, visual impairment imposed significant adverse effect on five vision-specific items and had no significant relationship with the eight dimensions of SF-36. Defective stereopsis in the elderly imposes no significant adverse effect on vision-related quality of life. However, subjects may feel more exhausted in accomplishing their usual tasks.


Spontaneous buckling of contractile poroelastic actomyosin sheets.
Shape transitions in developing organisms can be driven by active stresses, notably, active contractility generated by myosin motors. The mechanisms generating tissue folding are typically studied in epithelia. There, the interaction between cells is also coupled to an elastic substrate, presenting a major difficulty for studying contraction induced folding. Here we study the contraction and buckling of active, initially homogeneous, thin elastic actomyosin networks isolated from bounding surfaces. The network behaves as a poroelastic material, where a flow of fluid is generated during contraction. Contraction starts at the system boundaries, proceeds into the bulk, and eventually leads to spontaneous buckling of the sheet at the periphery. The buckling instability resulted from system self-organization and from the spontaneous emergence of density gradients driven by the active contractility. The buckling wavelength increases linearly with sheet thickness. Our system offers a well-controlled way to study mechanically induced, spontaneous shape transitions in active matter.


Species-specific differences in the toxicity of rhodamine 123 towards cultured mammalian cells.
The toxicity of cationic fluorescent dye, rhodamine 123, towards a number of independently established cell lines from three different species, namely human, mouse, and Chinese hamster, has been examined. All of the cell lines from any one species that were examined were found to exhibit similar sensitivities towards rhodamine 123 and no appreciable differences were observed between the normal and transformed cell types. However, in comparison to the cells of human origin, mouse and Chinese hamster cell lines exhibited about 10-fold and 70-fold higher resistance, respectively, and these differences appeared to be species related. In contrast to rhodamine 123, no differences in relative toxicities for these cell lines were observed for the structurally related neutral dye, rhodamine B. Fluorescence studies with rhodamine 123 show that in comparison to mouse and Chinese hamster cells, the more sensitive human cells show much higher uptake/binding of the drug, and a good correlation was seen in these studies between the extent of dye uptake/binding and the relative sensitivities of cell lines to rhodamine 123. These results provide evidence that the observed species-related differences in cellular toxicities are due to differences in the cellular uptake/binding of the dye.


Effect of gluten-free diet and adherence on growth and diabetic control in diabetics with coeliac disease.
To study the effect of gluten-free diet on growth and diabetic control of children with type 1 diabetes mellitus and coeliac disease. Twenty one children (mean age 7.5 years, range 1.6-12.9) with type 1 diabetes, primarily initially identified on the basis of symptoms and consecutively diagnosed with coeliac disease by biopsy over a 10 year period, were matched by sex, age at onset, and duration of diabetes with two diabetic controls without coeliac disease. Weight, height, haemoglobin A1c, and insulin requirements were measured before and for 12 months after the diagnosis and treatment of coeliac disease. Dietary awareness and adherence were assessed by structured questionnaire. A gluten-free diet resulted in a significant increase in weight-for-age z scores at 12 months after diagnosis (mean increase in z score 0.33) and in BMI (mean increase in z score 0.32). Increases in height did not achieve statistical significance. Controls showed no significant changes in weight, height, or BMI over the same period. Insulin dosage at diagnosis was less in coeliacs than in controls (mean difference 0.16 units/kg/day), but was similar to controls once a gluten-free diet had been established. Questionnaires were obtained in 20 patients. There appeared to be a relation between dietary awareness/adherence and growth parameters, but the small number of patients with "poor/fair" dietary adherence prevented meaningful analysis of this group. Identification and dietary treatment of coeliac disease in children with diabetes improved growth and influenced diabetic control. Evaluation of the outcome of treatment of coeliac disease in diabetics should include assessments of gluten intake.


Effect of exercise training and food restriction on endothelium-dependent relaxation in the Otsuka Long-Evans Tokushima Fatty rat, a model of spontaneous NIDDM.
We investigated whether endothelial function may be impaired in the Otsuka Long-Evans Tokushima Fatty (OLETF) rat, a model of spontaneous NIDDM. The effect of exercise training and food restriction on endothelial function was also studied. OLETF rats were divided into three groups at age 16 weeks: sedentary, exercise trained, and food restricted (70% of the food intake of sedentary rats). Otsuka Long-Evans Tokushima rats were used as the age-matched nondiabetic controls. Endothelium-dependent relaxation of the thoracic aorta induced by histamine was significantly attenuated in the sedentary or food-restricted rats, and exercise training improved endothelial function. Relaxation induced by sodium nitroprusside, a donor of nitric oxide, did not differ significantly among groups. Both exercise training and food restriction significantly suppressed plasma levels of glucose and insulin and serum levels of triacylglycerol and cholesterol and reduced the accumulation of abdominal fat. Insulin sensitivity, as measured by the hyperinsulinemic-euglycemic clamp technique, was significantly decreased in sedentary rats but was enhanced in exercise-trained and food-restricted rats. The urinary excretion of nitrite was significantly decreased in sedentary and food-restricted rats compared with nondiabetic rats and was significantly increased in exercise-trained rats. These results indicate that exercise training, but not food restriction, prevents endothelial dysfunction in NIDDM rats, presumably due to the exercise-induced increase in the production of nitric oxide.


Treatment of tetanus: an open study to compare the efficacy of procaine penicillin and metronidazole.
A prospective, open, non-randomised clinical trial was carried out to compare the efficacy of procaine penicillin with metronidazole in the treatment of moderate tetanus among 173 patients. Patients in the metronidazole group had a significantly lower mortality rate, a shorter stay in hospital, and an improved response to treatment. These results establish the value of antimicrobial treatment in the management of tetanus and show that metronidazole is more efficacious than penicillin in this respect.


[Stanford type A acute aortic dissection with congenital complete absence of the left pericardium; report of a case].
A 52-year-old woman who presented with acute onset of chest pain was diagnosed with Stanford type A acute aortic dissection by computed tomography at another hospital. She was referred to our department for emergency surgery. The left pericardium visualized via a median sternotomy was clearly defective, and the left phrenic nerve was located ventral to the defect. The ascending aorta and total arch were replaced with an aortic valve and a prosthetic graft, respectively. Postoperative chest radiography excluded left phrenic nerve palsy. The postoperative course was uneventful and the patient was discharged on postoperative day 17.


American College of Surgeons Resident Objective Structured Clinical Examination: a national program to assess clinical readiness of entering postgraduate year 1 surgery residents.
This report describes the development, initial implementation, and reliability of American College of Surgeons Resident Objective Structured Clinical Examination (ACS OSCE). Variability in clinical knowledge and skills of entering surgery residents has been demonstrated. The ACS OSCE was developed to evaluate and help remediate residents' knowledge and skills in managing patients with life-threatening conditions. A task force of surgeons and professional educators developed 10 standardized clinical case stations, evaluation checklists, and rating scales. Standardized patients (SPs) evaluated each resident's clinical skills (history taking, physical examination, communication, and SP-global scores). Residents completed checklists on diagnosis and management. Coefficient alpha and item-total correlations were used, respectively, to assess internal consistency of metrics and station validity. The resident's overall performance for each station was calculated by combining scores of the individual skills. Analysis of variance compared performance across different institutions. A total of 103 postgraduate year 1 residents from 7 institutions completed the OSCE. Reliability coefficients of skills ranged from 0.38 for diagnosis to 0.68 for global scores. For overall performance on individual stations, the reliability coefficients ranged from 0.51 to 0.82. Using total percent correct scores from highly reliable stations (α > 0.8), wide variability in resident performance was demonstrated within and between the 7 institutions. The ACS OSCE was successfully implemented across diverse institutions. It had moderate reliability and demonstrated variability among entering surgery residents. The ACS OSCE is now available for broader implementation. It should help reduce resident variability and address the requirements of Accreditation Council for Graduate Medical Education for resident supervision.


Anti-hypertensive drugs in children and adolescents.
Worldwide the prevalence of essential hypertension in children and adolescents continues to increase. Traditionally providers have used "off-label" drugs to treat pediatric hypertension, meaning that rigorous clinical trials of these drugs have not been specifically performed in pediatric patient populations. Consequently providers have extrapolated dosing, safety and efficacy from trials in adults. This practice is sub-optimal as children demonstrate unique differences in drug metabolism and response. Use of unstudied or understudied drugs increases risk of adverse events and/or can lead to sub-optimal efficacy. Recognizing these concerns, regulatory agencies have created financial incentives for industry to conduct pediatric clinical trials. These incentives, coupled with the emerging pediatric hypertension epidemic, have spurred over 30 clinical trials of anti-hypertensive drugs over the past 15 years and have resulted in labeling of 10 new drugs by the United States Food and Drug Administration for treatment of hypertension in children and adolescents. Unfortunately the financial incentive structures focus on newer drugs and drug classes. Consequently there is now a relative dearth of trial data for older but sometimes commonly prescribed pediatric antihypertensive drugs. This article reviews recent pediatric antihypertensive drug trials with a focus on trial design and endpoints, drug dosing, safety, efficacy and specific drug indications. We also review the available data and experience for some of the more commonly prescribed, but less well studied "older" pediatric antihypertensive drugs.


Oxidation of alkyl-substituted cyclic hydrocarbons by a Nocardia during growth on n-alkanes.
Nocardia 107-332, a soil isolate, oxidizes short-chain alkyl-substituted cyclic hydrocarbons to cyclic acids while growing on n-alkanes. Cyclic acids are produced also from relatively long-chain alkyl-substituted cyclics such as n-nonylbenzene or n-dodecylbenzene which alone support growth in a mineral-salts medium. omega-Oxidation of the alkyl substituents is followed by beta-oxidation. It is of particular interest that cyclic acids such as cyclohexaneacetic and phenylacetic with C(2) residual carboxylic acid substituents are resistant to further oxidation by the nocardia but cyclic acids with C(1) or C(3) substituents are readily oxidized and utilized for growth. The specificity of microbial oxidations is demonstrated by the conversion of p-isopropyltoluene (p-cymene) to p-isopropylbenzoic acid in n-alkane, growth-supported nocardia cultures.


Two Oyster Species That Show Differential Susceptibility to Virus Infection Also Show Differential Proteomic Responses to Generic dsRNA.
Viral diseases are a significant cause of mortality and morbidity in oysters, resulting in significant economic losses. We investigated the proteomic responses of these two species of oysters to generic double-stranded RNAs (poly I:C and poly A:U). Analysis of proteomic data using isobaric tags for relative and absolute quantitaion (iTRAQ) indicated that there were significant differences in the proteomic responses of the two oyster species resulting from this treatment. Gene ontology analysis showed that several biological processes, cellular components, and molecular function were unique to the different data sets. For example, a number of proteins implicated in the TLR signaling pathway were associated with the Saccostrea glomerata data set but were absent in the Crassostra gigas data set. These results suggest that the differences in the proteomic responses to dsRNA may underpin the biological differences in viral susceptibility. Molecular targets previously shown to be expressed in C. gigas in response to OsHV1 infections were not present in our proteomic data sets, although they were present in the RNA extracted from the very same tissues. Taken together, our data indicate that there are substantial disparities between transcriptomic and proteomic responses to dsRNA challenge, and a comprehensive account of the oysters' biological responses to these treatments must take into account that disparity.


Branching of the foramen rotundum. A rare variation of the sphenoid.
The human orbit communicates with the middle cranial fossa through several canals and openings. Some of them (optic canal, superior orbital fissure) are constant, others (meningo-orbital foramen, Warwick's foramen, metoptic canal) are less frequent. Here we report a rare variation of the foramen rotundum which, opening into the orbit with a branching canal, represented a further connecting pathway between the orbit and the middle cranial fossa. Such variation was detected in about 1.06% of individuals and it was almost always located on the right side. Only in one cases it could be found left-sided and in another skull it was spotted bilaterally. The vari- ation consisted of the branching of a 5 mm long canal from the lateral wall of the foramen rotun- dum that opened into the orbit. In general the diameter of the canal was comprised between 0.5 and 0.6 mm but it could be as large as 1 mm or as thin as 0.2 mm. The canal, straight and directed slightly superolaterally, likely transmitted the zygomatic nerve and/or part of the infraorbital nerve. To our knowledge, an independent entrance through a dedicated canal of such nerves has never been reported. The surgeons operating in this region, either neurosurgeons or ophthalmologists, should be aware of the possible variation in the course of these nerves.


Insertion site occupancy by stx2 bacteriophages depends on the locus availability of the host strain chromosome.
Shiga toxin-producing Escherichia coli (STEC) is an emergent pathogen characterized by the expression of Shiga toxins, which are encoded in the genomes of lambdoid phages. These phages are infectious for other members of the Enterobacteriaceae and establish lysogeny when they integrate into the host chromosome. Five insertion sites, used mainly by these prophages, have been described to date. In the present study, the insertion of stx(2) prophages in these sites was analyzed in 168 STEC strains isolated from cattle. Additionally, insertion sites were determined for stx(2) phages which (i) converted diverse laboratory host strains, (ii) coexisted with another stx(2) prophage, and (iii) infected a recombinant host strain lacking the most commonly used insertion site. Results show that depending on the host strain, phages preferentially use one insertion site. For the most part, yehV is occupied in STEC strains while wrbA is preferentially selected by the same stx phages in E. coli laboratory strains. If this primary insertion site is unavailable, then a secondary insertion site is selected. It can be concluded that insertion site occupancy by stx phages depends on the host strain and on the availability of the preferred locus in the host strain.


[Activity and induction of CYP2B, CYP2C, and CYP3A in tissues of cyclophosphane-sensitive and resistant neoplasms and the liver of neoplasm-carrying mice].
The activities of three cytochrome P450 families involved in metabolic transformation of cyclophosphamide (CP) (CYP2B and CYP2C responsible for metabolic activation of CP and CYP3A responsible for inactivation of CP) have been investigated in lymphosarcoma and liver microsomes of tumor-bearing CBA mice. Two strains of mouse lymphosarcoma distinguished by their sensitivity to cytostatic action of CP were used in this study for implantation in mice femur muscle. There was certain relationship between CP resistance of lymphosarcoma and tumor P450s activity. CYP2B, CYP2C and CYP3A activities in the CP sensitive tumor were comparable to those in liver, and CYP2B, CYP2C were induced by phenobarbital and dexamethasone. CYP2B and CYP2C in the CP resistant tumor were inactive and only slightly induced by dexamethasone. CYP3A activity was lower than in LS tumor and unchanged during drug treatment. Implantation of LS and RLS tumor in mice caused different effects on P450 activities. LS insignificantly influenced liver CYP2B, CYP2C and CYP3A activities and their inducibility by phenobarbital and dexamethasone was similar to that obtained in liver of mice without tumor. At the same time, CYP2B and CYP2C activity in liver of RLS-bearing mice were essentially reduced, the activity CYP3A remained unchanged, and inducibility of CYP2B, CYP2C and CYP3A by phenobarbital and dexamethasone was similar to that in liver of mice without tumor. These results prove the role of cytochromes P450 activating CP in formation drug resistant phenotype of mice lymphosarcoma and suggest possibility of overcoming of this resistance using cytochrome P450 inducers.


Post-cesarean section pain secondary to intussuscepting colonic adenocarcinoma.
The differential diagnosis for lower abdominal and pelvic pain following Cesarean section includes many causes, such as endometritis, abscess, pelvic hematoma, wound complications, pelvic vein thrombophlebitis, gastrointestinal dysfunction and obstruction. Colonic obstruction secondary to intussusception is a rare cause. We present a case of post-Cesarean section pain in a 26-year-old patient due to obstructing colonic intussusception secondary to colonic adenocarcinoma. Review of the literature failed to identify a previous case report of colonic adenocarcinoma with intussusception presenting early in the postpartum period. The diagnosis was initially made by ultrasound, and later corroborated by computed tomography, barium enema and laparotomy.


Oil production and groundwater quality in the Edwards-Trinity Plateau Aquifer, Texas.
Chloride concentrations and chloride/bromide ratios from 198 water wells in the Edwards-Trinity Plateau Aquifer were compiled, mapped, and evaluated within the context of regional geology and land use. The study area occupies eight counties in west-central Texas, within which oil production and agriculture are predominant land uses. Samples from 49 wells had chloride concentrations above the 250 mg/l secondary drinking water standard, 22 samples had greater than 500 mg/l chloride, and 9 samples exceeded 1000 mg/l chloride. Of the 22 samples above 500 mg/l chloride, 10 had relatively low chloride/bromide ratios of less than 300, consistent with oilfield brine, and 2 had ratios above 2000, consistent with groundwater impacted by evaporite dissolution. The remaining ten samples had chloride/bromide ratios ranging from 300 to 2000, consistent with partial mixing of unimpaired groundwater with evaporite-laden water. There were no significant correlations between chloride concentration and well depth, inconsistent with contaminants originating at the land surface. Results of this study suggest that evaporite dissolution and oilfield brine locally impact the Edwards-Trinity Plateau Aquifer, but the problem is not regionally pervasive.


Dietary protein and the renin-angiotensin system in chronic renal allograft rejection.
We examined the effects of dietary protein restriction in fourteen patients with chronic kidney rejection. The patients were randomly assigned, using a crossover design to two 11-day periods, one on a low-protein diet (0.55 g/kg/day) and the other on a high-protein diet (2 g/kg/day). The low protein diet was associated with a significant improvement in glomerular permselectivity without any change in blood pressure, glomerular filtration rate, or renal plasma flow. The low protein diet was also associated with a significant reduction in plasma renin activity. Acute converting enzyme inhibition decreased proteinuria when administered at the end of the high protein diet, but had no additional antiproteinuric effect when given at the end of the low protein diet. Comparable reductions in blood pressure with hydralazine had no effect on proteinuria. Protein restriction was also associated with modest but significant fall in serum proteins. In conclusion, dietary protein restriction may improve the course of renal failure in chronic rejection partly by suppressing the renin-angiotensin system. Studies are needed to establish the safe level of dietary protein restriction in these patients and to assess the efficacy of such restriction in slowing the progression of renal failure.


A density functional theory study clarifying the reactions of conjugated ketenes with formaldimine. A plethora of pericyclic and pseudopericyclic pathways.
The reactions of vinylketene (1a), imidoylketene (1b), and formylketene (1c) with formaldimine (2) were studied at the B3LYP/6-31G* level. For the cycloadditions of these conjugated ketenes with 2, several possible pathways to both [4 + 2] and [2 + 2] products were examined. The lowest energy [2 + 2] pathways are, in most cases, calculated to be stepwise, forming the products via rate-determining conrotatory electrocyclization of zwitterionic intermediates. However, concerted transition structures analogous to the ketene plus ethene [2 + 2] cycloaddition reaction were also located; the existence of multiple transition states offers a resolution to a long-standing controversy regarding the mechanism of ketene plus imine cycloadditions. Both stepwise and concerted [4 + 2] pathways were calculated for 2b and for 2c; both these pathways are pseudopericyclic. The inherently low barriers associated with pseudopericyclic transition states provide an explanation of the experimental preference for [4 + 2] cycloadditions of alpha-oxoketenes and predict [4 + 2] cycloadditions should also be favored for imidoylketenes. For a vinylketene constrained to a Z-geometry, the concerted [4 + 2] cycloaddition is also predicted to be the lowest energy pathway. An explanation is offered for the unusual thermal equilibration from a six-membered ring (3d) to a four-membered ring (4d) observed by Sato et al. Transition structures for facile pseudopericyclic 1,3- and 1,5-hydrogen shifts in the zwitterions were also calculated.


Building a solid GLP foundation: implementing shared training programs between the QAU and study personnel.
Quality assurance representatives and study personnel are equally responsible for conducting preclinical studies in compliance with good laboratory practices (GLPs). To provide all employees with a solid understanding of GLP requirements we have implemented a system of shared training programs for the quality assurance unit (QAU) and study personnel. Biologists and chemists complete a three-phase training module that encompasses GLP history, roles and responsibilities of the QAU, and QAU procedures specific to Wildlife International, Ltd. Study directors work with experienced QA trainers and are provided mock auditing assignments, including data, reports, and in-process and facility inspections. QA personnel are in turn trained by qualified study personnel in principal scientific concepts, testing guidelines, and study procedures that will be observed when performing in-process inspections and data audits. Also, as permanent positions become available, selected individuals from the QAU may assume responsibilities in various departments as study directors or laboratory supervisors, and study directors may assume responsibilities as quality assurance representatives. At Wildlife International, Ltd., these shared training programs provide a mutual understanding and knowledge of GLP requirements and their application while promoting respect and harmony between the QAU and study personnel.


Bilateral hemicraniectomy in non-penetrating traumatic brain injury.
Traumatic brain injury is a heterogeneous entity that encompasses both surgical and non-surgical conditions. Surgery may be indicated with traumatic lesions such as hemorrhage, fractures, or malignant cerebral edema. However, the neurological exam may be clouded by the effects of medications administered in the field, systemic injuries, and inaccuracies in hyperacute prognostication. Typically, neurological injury is considered irreversible if diffuse loss of grey/white matter differentiation or if brainstem hemorrhage (Duret hemorrhage) exists. We aim to characterize a cohort of patients undergoing bilateral hemicraniectomy for severe traumatic brain injury. A retrospective consecutive cohort of adult patients undergoing craniectomy for trauma was established between the dates of January 2008 and November 2011. The primary outcome of the study was in-hospital mortality. Secondary outcomes were ICU length of stay, surgical complications, and Glasgow Outcome Score at most recent follow-up. During the study period, 210 patients undergoing craniectomy for traumatic mass-occupying lesion (epidural hematoma, subdural hematoma, or parenchymal contusion) were analyzed. Of those, 9 met study criteria. In-hospital mortality was 67% (6 of 9 patients). The average ICU length of stay was 12 days. The GOS score was 3 in surviving patients. Bilateral hemicraniectomy is a heroic intervention for patients with severe TBI, but can be a life-saving procedure.


Front-line treatment patterns in multiple myeloma: An analysis of U.S.-based electronic health records from 2011 to 2019.
Multiple myeloma (MM) treatment options have evolved rapidly, but how new agents are incorporated into treatment decisions in current practice is not well understood. This study examined prescribing trends of physicians treating newly diagnosed MM and treatment outcomes in the United States. Electronic health record data from 6271 adult patients diagnosed with MM and receiving initial treatment between 1 January 2011 and 31 January 2020 were derived from the Flatiron Health electronic-health record de-identified database. The number/types of agents included in therapy regimens, time to next treatment (TTNT), and overall survival (OS) were assessed. Subgroups were analyzed by the International Staging System (ISS) disease stage at diagnosis, stem cell transplant eligibility and timing, and practice type. Exploratory prognostic models evaluated the association between baseline covariates and time-to-event outcomes. The proportion of patients receiving triplet therapies increased from 2011 (36%) to 2019 (72%) as those receiving initial monotherapy or doublet therapy decreased. Overall, the most prevalent triplet regimen consisted of an immunomodulatory drug (IMiD), a proteasome inhibitor, and a steroid. From 2017 to 2019, median TTNT from front-line to second-line was longer in patients with ISS stage I versus stages II/III, and in those receiving IMiD-containing doublet or triplet therapies versus other combinations. Overall median OS was 56 months and increased from 2011 to 2014, after which median OS was not yet reached. Age, ISS stage, and high-risk status were prognostic for both OS and TTNT, while sex, practice type, and ECOG status were prognostic for OS only.


Prevalence and burden of health problems in competitive adolescent distance runners: A 6-month prospective cohort study.
To describe all health problems (injuries and illnesses) in relation to type, location, incidence, prevalence, time loss, severity, and burden, in competitive adolescent distance runners in England. Prospective observational study: 136 competitive adolescent distance runners (73 female athletes) self-reported all health problems for 24-weeks between May and October 2019. Athletes self-reported health problems using the Oslo Sports Trauma Research Centre Questionnaire on Health Problems. The incidence of running-related injury per 1,000 hours of exposure was markedly higher, compared to previous research. At any time, 24% [95% Confidence Intervals (CI): 21-26%] of athletes reported a health problem, with 11% [95% CI: 9-12%] having experienced a health problem that had substantial negative impact on training and performance. Female athletes reported noticeably more illnesses, compared to male athletes, including higher prevalence, incidence, time loss, and severity. The most burdensome health problems, irrespective of sex, included lower leg, knee, and foot/toes injuries, alongside upper respiratory illnesses. The mean weekly prevalence of time loss was relatively low, regardless of health problem type or sex. Competitive adolescent distance runners are likely to be training and competing whilst concurrently experiencing health problems. These findings will support the development of injury and illness prevention measures.


Modelling biofilm anaerobic reactor with effluent from hydrolytic/acidogenic reactor as substrate.
This work presents modelling of an anaerobic biofilm reactor using ceramic bricks as support. The results were compared with the experimental data. It was observed that the substrate concentration curves showed the same tendency. The methane formation curves showed significant differences. The substrate removal efficiency was 83%. In the steady state, the experimental data were higher than the model, from the result the substrate degrading bacteria grew enough to reach biofilm and that the effect of the shear stress was more significant as the biofilm increased in thickness. To the methane production, the model in steady state reached a maximum value of 0.56 m3 CH4/m3 *d and the experimental data reached 0.42 (m3 CH4/m3 * d). The biofilm thickness calculated by the model was 14 μm.


Prevalence of the metabolic syndrome in German women with polycystic ovary syndrome.
The aim of our study was to evaluate the prevalence of the metabolic syndrome (MBS) according to the current International Diabetes Federation definition in German PCOS women. Four hundred and eleven PCOS patients (age 28+/-6.3 years) and 82 controls (age 28+/-7.5 years) were evaluated for anthropometric and metabolic parameters by physical examination, blood testing and a personal interview including family history. A subgroup analysis of controls with BMI-matched PCOS women (BMI 22.9+/-2.8 kg/m (2)) was performed to detect PCOS specific differences in metabolic variables between the groups. The MBS was found in 33.8% of PCOS women compared to 7.3% in the control group. Parameters of insulin resistance, lipid-and glucose metabolism, mean values of all criteria of the MBS as well as the prevalence of the MBS were significantly different between the entire PCOS cohort and controls, but did not differ between BMI-matched PCOS women and controls. In addition, the prevalence of the MBS increased with age. Moreover, in PCOS women an increase in BMI and insulin resistance was accompanied by a further significant increase in the severity of clinical and biochemical hyperandrogenism. In PCOS women, while one out of three PCOS women had the MBS, the presence of metabolic abnormalities did not appear to be associated with PCOS per se, but rather correlated with age and the degree of obesity.


Drinking Water Quality and Provision in Six Low-Income, Peri-Urban Communities of Lusaka, Zambia.
Lusaka, Zambia, is a rapidly growing city located on a vulnerable karstic dolomite aquifer that provides most of the city's drinking water. Over 65% of residents live in peri-urban communities with inadequate sanitation leading to widespread groundwater contamination and the spread of waterborne diseases such as cholera. To fill the water service gap, Water Trusts were created: public/private partnerships designed to provide clean water to peri-urban community residents. Water Trusts extract groundwater via boreholes, treat it with chlorine, and distribute it to residents via public kiosks. We investigated the efficacy of drinking water provision to residents in six of Lusaka's peri-urban communities with Water Trusts. Water samples were collected from Water Trust boreholes and kiosks, privately owned boreholes, and shallow wells during four sampling efforts. To assess potential risk to human health, water samples were analyzed for Escherichia coli (E. coli) and nitrate. Shallow wells were significantly more contaminated with E. coli than Water Trust boreholes, kiosks, and private boreholes (Tukey-adjusted p values of 9.9 × 10-6). Shallow wells and private boreholes had significantly higher nitrate-N concentrations (mean of 29.6 mg/L) than the Water Trust boreholes and kiosks (mean of 8.8 mg/L) (p value = 1.1 × 10-4). In 2016, a questionnaire was distributed to Water Trust managers to assess their ability to meet demands. In the six communities studied, Water Trusts served only about 60% of their residents. Water Trusts provide a much safer alternative to shallow wells with respect to nitrate and E. coli, but they struggle to keep pace with growing demand.


Implants with original and non-original abutment connections.
To test in vitro the mechanical resistance, rotational misfit and failure mode of three original implant-abutment connections and to compare them to two connections between non-original abutments connected to one of the original implants. Three different implants with small diameters (3.3 mm for Straumann Roxolid, 3.5 mm for Nobel Biocare Replace and Astra Tech Osseospeed TX) were connected with individualized titanium abutments. Twelve implants from each system were connected to their original abutments (Straumann CARES, Nobel Biocare Procera, Astra Tech Atlantis). Twenty-four Roxolid implants were connected with non-original abutments using CAD/CAM procedures from the other two manufacturers (12 Nobel Biocare Procera and 12 Astra Tech Atlantis). For the critical bending test, a Zwick/Roell 1475 machine and the Xpert Zwick/Roell software were used. The rotational misfit varied when comparing the different interfaces. The use of non-original grade V titanium abutments on Roxolid implants increased the force needed for deformation. The fracture mode was different with one of the original connections. Non-original abutments differ in design of the connecting surfaces and material and demonstrate higher rotational misfit. These differences may result in unexpected failure modes.


Functional neuroanatomy underlying the clinical subcategorization of minimally conscious state patients.
Patients in a minimally conscious state (MCS) show restricted signs of awareness but are unable to communicate. We assessed cerebral glucose metabolism in MCS patients and tested the hypothesis that this entity can be subcategorized into MCS- (i.e., patients only showing nonreflex behavior such as visual pursuit, localization of noxious stimulation and/or contingent behavior) and MCS+ (i.e., patients showing command following).Patterns of cerebral glucose metabolism were studied using [(18)F]-fluorodeoxyglucose-PET in 39 healthy volunteers (aged 46 ± 18 years) and 27 MCS patients of whom 13 were MCS- (aged 49 ± 19 years; 4 traumatic; 21 ± 23 months post injury) and 14 MCS+ (aged 43 ± 19 years; 5 traumatic; 19 ± 26 months post injury). Results were thresholded for significance at false discovery rate corrected p < 0.05.We observed a metabolic impairment in a bilateral subcortical (thalamus and caudate) and cortical (fronto-temporo-parietal) network in nontraumatic and traumatic MCS patients. Compared to MCS-, patients in MCS+ showed higher cerebral metabolism in left-sided cortical areas encompassing the language network, premotor, presupplementary motor, and sensorimotor cortices. A functional connectivity study showed that Broca's region was disconnected from the rest of the language network, mesiofrontal and cerebellar areas in MCS- as compared to MCS+ patients.The proposed subcategorization of MCS based on the presence or absence of command following showed a different functional neuroanatomy. MCS- is characterized by preserved right hemispheric cortical metabolism interpreted as evidence of residual sensory consciousness. MCS+ patients showed preserved metabolism and functional connectivity in language networks arguably reflecting some additional higher order or extended consciousness albeit devoid of clinical verbal or nonverbal expression.


Lack of Ikaros Deregulates Inflammatory Gene Programs in T Cells.
CD4 Th cells are organizers of the immune response, directing other immune cells to initiate and maintain effective humoral and cellular immunity. CD4 T cells differentiate into distinct Th effector or regulatory subsets in response to signals delivered to them during the course of infection. Ikaros is a transcription factor that is expressed in blood cells from the level of the hematopoietic stem cell. It is required for normal thymic T cell development and serves as a tumor suppressor, as lack of Ikaros in developing lymphoid cells results in leukemia. To study the role of Ikaros in CD4 T cell differentiation and function, an Ikaros conditional knockout mouse was developed such that Ikaros expression was deleted specifically in mature T cells, thus avoiding defects observed in germline Ikaros mutant mice. Using this model system, we have shown that in the absence of Ikaros, CD4 T cells are able to attain Th1, Th2, and Th17, but not inducible regulatory T, cell fates. However, they show enhanced expression of a cohort of proinflammatory cytokines, resulting in differentiation of Th17 cells with a phenotype that has been associated with autoimmunity and pathological inflammation. In addition, we define Ikaros as a repressor of the gene program associated with the response to type I IFNs, another key pathway whose deregulation is linked to autoimmunity. Taken together, these data definitively define Ikaros as a critical regulator at the center of the inflammatory response in T cells and highlight a potential role in suppressing autoimmunity.


Discordant diagnostic criteria for pneumonia in COPD trials: a review.
Inhaled corticosteroids (ICS) have a class effect of increasing pneumonia risk in patients with COPD. However, pneumonia incidence varies widely across clinical trials of ICS use in COPD. This review clarifies methodological differences in defining and recording pneumonia events in these trials and discusses factors that could contribute to the varying pneumonia incidence. Literature searches and screening yielded 40 relevant references for inclusion. Methods used to capture pneumonia events in these studies included investigator-reported pneumonia adverse events, standardised list of signs or symptoms, radiographic confirmation of suspected cases and/or confirmation by an independent clinical end-point committee. In general, more stringent pneumonia diagnosis criteria led to lower reported pneumonia incidence rates. In addition, studies varied in design and population characteristics, including exacerbation history and lung function, factors that probably contribute to the varying pneumonia incidence. As such, cross-trial comparisons are problematic. A minimal set of standardised criteria for diagnosis and reporting of pneumonia should be used in COPD studies, as well as reporting of patients' pneumonia history at baseline, to allow comparison of pneumonia rates between trials. Currently, within-trial comparison of ICS-containing versus non-ICS-containing treatments is the appropriate method to assess the influence of ICS on pneumonia incidence.


Stochastic Learning for Sparse Discrete Markov Random Fields with Controlled Gradient Approximation Error.
We study the L 1-regularized maximum likelihood estimator/estimation (MLE) problemfor discrete Markov random fields (MRFs), where efficient and scalable learning requires both sparse regularization and approximate inference. To address these challenges, we consider a stochastic learning framework called stochastic proximal gradient (SPG; Honorio 2012a, Atchade etal. 2014, Miasojedow and Rejchel 2016). SPG is an inexact proximal gradient algorithm [Schmidt et al., 2011], whose inexactness stems from the stochastic oracle (Gibbs sampling) for gradient approximation - exact gradient evaluation is infeasible in general due to the NP-hard inference problem for discrete MRFs [Koller and Friedman, 2009]. Theoretically, we provide novel verifiable bounds to inspect and control the quality of gradient approximation. Empirically, we propose the tighten asymptotically (TAY) learning strategy based on the verifiable bounds to boost the performance of SPG.


Mycobacterium elephantis sp. nov., a rapidly growing non-chromogenic Mycobacterium isolated from an elephant.
A strain isolated from a lung abscess in an elephant that died from chronic respiratory disease was found to have properties consistent with its classification in the genus Mycobacterium. An almost complete sequence of the 165 rDNA of the strain was determined following the cloning and sequencing of the amplified gene. The sequence was aligned with those available on mycobacteria and phylogenetic trees inferred by using three tree-making algorithms. The organism, which formed a distinct phyletic line within the evolutionary radiation occupied by rapidly growing mycobacteria, was readily distinguished from members of validly described species of rapidly growing mycobacteria on the basis of its mycolic acid pattern and by a number of other phenotypic features, notably its ability to grow at higher temperatures. The type strain is Mycobacterium elephantis DSM 44368T.


Description of Caldalkalibacillus uzonensis sp. nov. and emended description of the genus Caldalkalibacillus.
Strain JW/WZ-YB58T, a thermophilic (42-64 degrees C), aerobic, alkalitolerant (pH25 degrees C 6.4-9.7), heterotrophic, sporulating, retarded-peritrichously flagellated and slightly curved rod-shaped bacterium, was isolated from the hot spring Zarvarzin II in the East Thermal Field of the Uzon Caldera, Kamchatka (Far East Russia). The isolate tolerated high concentrations of CO. The major membrane phospholipid fatty acids of JW/WZ-YB58T included iso-C15 : 0 (24.5 %), anteiso-C15 : 0 (18.3 %) and iso-C17 : 0 (17.5 %). The G+C content of the genomic DNA is 45 mol% (HPLC method). Based on 16S rRNA gene sequence analysis and physiological properties, isolate JW/WZ-YB58T (=ATCC BAA-1258T =DSM 17740T) is proposed as the type strain of Caldalkalibacillus uzonensis sp. nov. In contrast to the type species Caldalkalibacillus thermarum, a catalase-reaction-positive aerobe, C. uzonensis was catalase-reaction-negative; thus the description of the genus Caldalkalibacillus is emended to include a catalase-reaction-negative species.


Informed guessing in change detection.
Provided stimuli are highly distinct, the detection of changes between two briefly separated arrays appears to be achieved by an all-or-none process where either the relevant information is in working memory or observers guess. This observation suggests that it is possible to estimate the average number of items an observer was able to retain across a series of trials, a potentially highly informative cognitive characteristic. For each version of the change detection paradigm, for this estimate to be accurate, it is important to specify how observers use the information available to them. For some instantiations of this task it is possible that observers use knowledge of the contents of working memory even when they are in a guessing state, rather than selecting between the response alternatives at random. Here we test the suggestion that observers may be able to use their knowledge of the number of items in memory to guide guessing in two versions of the change detection task. The four experiments reported here suggest that participants are, in fact, able to use the parameters of the task to update their base expectation of a change occurring to arrive at more informed guessing. (PsycINFO Database Record


Randomized clinical study using xenograft blocks loaded with bone morphogenetic protein-2 or autogenous bone blocks for ridge augmentation - A three-dimensional analysis.
To test whether or not the use of a xenogeneic block loaded with rhBMP-2 results in superior radiological and profilometric outcomes compared to an autogenous bone block. Twenty-four patients randomly received a xenogeneic block loaded with rhBMP-2 (test) or an autogenous bone block (control) for primary augmentation. The ridge width (RW) was evaluated by means of a CBCT scan after augmentation surgery and at 4 months, prior to implant placement. Surface scans were taken prior to augmentation and at 4 months for profilometric analyses. Data were analyzed with Wilcoxon-signed rank test, Mann-Whitney test, or nonparametric ANOVA models. The median RW after augmentation amounted to 7.13 mm (Q1 = 6.02; Q3 = 8.47) for test and 6.86 mm (Q1 = 5.99; Q3 = 8.95) for control. During 4 months of healing, the total RW decreased statistically significantly and measured 5.35 mm (Q1 = 4.53; Q3 = 6.7) for test and 5.15 mm (Q1 = 3.57; Q3 = 7.24) for control (p = 0.0005). The differences between the groups were not statistically significant (p > 0.5899). The buccal soft tissue contour slightly increased for test (0.83 mm; Q1 = 0.62; Q3 = 1.87) and control (1.16 mm; Q1 = 0.50; Q3 = 1.44). Both treatment modalities successfully increased the ridge width to a similar extent. The shrinkage during healing was not greater in the test than in the control group. The impact of hard tissue augmentation on the soft tissue contour was, however, minimal.


Bis-(2-ethylhexyl) Phthalate Increases Insulin Expression and Lipid Levels in Drosophila melanogaster.
Bis-(2-ethylhexyl) phthalate (DEHP) is one of the most widely used plasticizers, and human beings are exposed to DEHP via polyvinyl chloride (PVC) materials, medical equipment and even drinking water. While DEHP has been implicated to influence metabolism and endocrine functions, important questions remain about the molecular mechanisms of these effects. We employed the model organism Drosophila melanogaster and examined physiological, molecular and behavioural effects from DEHP-contaminated food. We found that DEHP, at levels comparable to human exposure, made male flies more resistant to starvation and increased lipid levels, while decreasing circulating carbohydrates. Moreover, DEHP-fed male flies had higher expression levels of an insulin-like peptide known to regulate metabolism, as well as the insulin receptor. Our results suggest that long-term DEHP feeding may induce diabetes-like dysfunctions. These findings provide a molecular background of how DEHP may have detrimental effects on metabolic functions.


Genistein inhibits tumor invasion by suppressing multiple signal transduction pathways in human hepatocellular carcinoma cells.
Genistein (Gen) exhibits anti-mutagenic and anti-metastatic activities in hepatoma cell lines. Gen has suppressive effects on tumor growth and angiogenesis in nude mice. Gen suppresses the enzymatic activity of matrix metalloproteinase (MMP)-9; however, the mechanism underlying its anti-invasive activity on hepatocellular carcinoma (HCC) cells is unclear. In this study, the possible mechanisms underlying Gen-mediated reduction of 12-O-Tetradecanoylphorbol-13-acetate (TPA)-induced cell invasion and inhibition of secreted and cytosolic MMP-9 production in human hepatoma cells (HepG2, Huh-7, and HA22T) and murine embryonic liver cells (BNL CL2) were investigated. Gen suppressed MMP-9 transcription by inhibiting activator protein (AP)-1 and nuclear factor-κ B (NF-κB) activity. Gen suppressed TPA-induced AP-1 activity through inhibitory phosphorylation of extracellular signal-related kinase (ERK) and c-Jun N-terminal kinase (JNK) signaling pathways, and TPA-stimulated inhibition of NF-κB nuclear translocation through IκB inhibitory signaling pathways. Moreover, Gen suppressed TPA-induced activation of ERK/phosphatidylinositol 3-kinase/Akt upstream of NF-κB and AP-1. Gen and its inhibition of multiple signal transduction pathways can control the invasiveness and metastatic potential of HCC.


Prevalence of polycystic ovaries in women with self-reported symptoms of oligomenorrhoea and/or hirsutism: Northern Finland Birth Cohort 1966 Study.
The aim of this study was to investigate the prevalence of polycystic ovaries (PCO) among women with self-reported oligomenorrhoea and/or hirsutism and to see whether women with symptoms and PCO have less favourable levels of biochemical markers than controls or women with symptoms and normal ovaries. The ultrasonographic ovarian morphology and the hormonal and metabolic profile of female cases with self-reported symptoms typical of polycystic ovary syndrome (PCOS) (n = 196) and asymptomatic controls (n = 67) at the age of 31 years were examined in a general population-based Northern Finland Birth Cohort 1966. The prevalence of PCO (37.3 versus 18.2%; P = 0.004) was significantly higher in the cases (oligomenorrhoea and/or hirsutism) than in the controls. PCO morphology was detected in 18.4% of those who reported only hirsutism, in 47.9% of those reporting only oligomenorrhoea, and in 70.4% of those reporting both symptoms. In the cases with PCO compared to (i) the controls and (ii) the cases without PCO, body mass index (P = 0.026 and P = 0.011), ovarian volume [right P = 0.001, left P = 0.208 (non-significant) and right P < 0.001, left P = 0.022], mean follicle number (P < 0.001 and P < 0.001), testosterone (P = 0.063 and P = 0.029), free androgen index (P = 0.007 and P = 0.013) and insulin (P = 0.033 and P = 0.040) were higher, and sex hormone-binding globulin (P = 0.039 and P = 0.068) and glucose:insulin ratio (P = 0.060 and P = 0.054) lower. Cases with PCO also had higher waist:hip ratio (P = 0.011), infertility rate (P = 0.005) and glucose (P = 0.045) and lower insulin-like growth factor-binding protein-1 (P = 0.012) than controls. The clinical, hormonal and metabolic characteristics did not differ significantly between cases without PCO and controls with the exception of infertility rate, which was significantly higher in the cases without PCO (26.4 vs. 10.0%; P = 0.009). In a general population, women with symptoms of oligomenorrhoea and/or hirsutism more often have PCO than asymptomatic women. Levels of biochemical and clinical markers in symptomatic women with PCO differed from and were less favourable than those in symptomatic women without PCO or asymptomatic women, implying an increased risk for health.


Differential Susceptibility of Catheter Biomaterials to Biofilm-Associated Infections and Their Remedy by Drug-Encapsulated Eudragit RL100 Nanoparticles.
Biofilms are the cause of major bacteriological infections in patients. The complex architecture of Escherichia coli (E. coli) biofilm attached to the surface of catheters has been studied and found to depend on the biomaterial's surface properties. The SEM micrographs and water contact angle analysis have revealed that the nature of the surface affects the growth and extent of E. coli biofilm formation. In vitro studies have revealed that the Gram-negative E. coli adherence to implanted biomaterials takes place in accordance with hydrophobicity, i.e., latex > silicone > polyurethane > stainless steel. Permanent removal of E. coli biofilm requires 50 to 200 times more gentamicin sulfate (G-S) than the minimum inhibitory concentration (MIC) to remove 90% of E. coli biofilm (MBIC90). Here, in vitro eradication of biofilm-associated infection on biomaterials has been done by Eudragit RL100 encapsulated gentamicin sulfate (E-G-S) nanoparticle of range 140 nm. It is 10-20 times more effective against E. coli biofilm-associated infections eradication than normal unentrapped G-S. Thus, Eudragit RL100 mediated drug delivery system provides a promising way to reduce the cost of treatment with a higher drug therapeutic index.


Asperger syndrome and autism: a comparative longitudinal follow-up study more than 5 years after original diagnosis.
Prospective follow-up study of 70 males with Asperger syndrome (AS), and 70 males with autism more than 5 years after original diagnosis. Instruments used at follow-up included overall clinical assessment, the Diagnostic Interview for Social and Communication Disorders, Wechsler Intelligence Scales, Vineland Adaptive Behavior Scales, and Global Assessment of Functioning Scale. Specific outcome criteria were used. Outcome in AS was good in 27% of cases. However, 26% had a very restricted life, with no occupation/activity and no friends. Outcome in the autism group was significantly worse. Males with AS had worse outcomes than expected given normal to high IQ. However, outcome was considerably better than for the comparison group of individuals with autism.


The pattern of benign gestational trophoblastic disease in Karachi.
A hospital based epidemiological study of benign gestational trophoblastic disease i.e., both complete and partial hydatidiform mole was undertaken at 8 hospitals. The frequency of the disease was found to be 3.89/1000 pregnancies and was found to be higher--1 in 237 deliveries in the economically deprived women admitted to a free Government Hospital, compared to only 1 in 471 deliveries in a Private, fee-for-service hospital. Risk factors identified, were: age above 35 years (OR = 7.39, CL 5.54-9.87); or under 20 years (OR = 2.14, CL = 1.60-2.85), history of previous molar pregnancy (OR = 18.44, CL = 49.4-74.09), past history of abortions (OR = 1.96, CL = 1.49-2.57) and recurrent abortions (OR = 3.26, CL = 1.82-5.77). Blood group A was also found to be a significant risk factor (OR = 1.6, CL = 1.01-2.53). Progression to gestational trophoblastic tumor was found in 3% patients with hydatidiform mole. A plea is made for earlier diagnosis at asymptomatic stage, to reduce morbidity; histopathological examination of all abortuses will help identify complete and partial moles which would otherwise be overlooked. Finally, improvement in follow-up system and establishment of a data base is recommended.


Morphological and molecular characteristics of living human fetuses between Carnegie stages 7 and 23: localization of inhibin mRNA alpha and beta a subunits by in-situ hybridization.
Localization of the mRNA alpha and beta a subunits of inhibin has previously been reported in the human gonads during the second trimester. Adrenal inhibin has also been reported in the second trimester for the alpha, beta a and beta b subunits. Investigations showing localization by in-situ hybridization during the first trimester have not been reported. The results have shown hybridization of the alpha and beta a subunits, throughout the period of development studied, in a variety of tissues including the dorsal and thoracic aortas and pericardium stages 13-22 (beta a subunit); liver stages 19-21 (beta a) and stages 21-22 (alpha); mesonephos stages 21 and 22 (beta a); gonad stages (alpha and beta a); adrenal stages 19-22 (alpha); surface ectoderm stages 16-22 (beta a); mesenchyme stages 16-22 (beta a); amnion stages 13-16 (beta a); yolk sac stage 12 (alpha and beta a); cartilage stages 19-22 (beta a); and nasal proliferation stages 21 and 22 (beta a). When compared with distribution of the protein subunits it was noted that more immunostaining activity was found, suggesting that that probes were not sufficiently sensitive enough to detect all levels of mRNA expressed. It can be surmised, therefore, that the lack of visual hybridization of the mRNA cannot preclude the possibility that it is not being translated within the tissue even though hybridization was not apparent.


Autoimmune polyglandular syndrome type II with co-manifestation of Addison's and Graves' disease in a 15-year-old boy: case report and literature review.
Background Autoimmune polyglandular syndrome type II (APS II) is defined as the combination of autoimmune adrenal insufficiency and autoimmune thyroid disease (AITD) and/or type I diabetes mellitus (T1DM) in the same patient. Case presentation A 15-year-old boy had a history of weight loss, nausea and vomiting, headache, restlessness, and tanned skin. He was diagnosed with Graves' disease. Two weeks after carbimazol therapy was commenced, he presented with adrenal crises (fever, arterial hypotension, hyponatremia, adrenocorticotropic hormone [ACTH] 1119.6 ng/mL [normal range <60] and low cortisol). He received hydrocortisone and fludrocortisone, and improved quickly. Thyroid-stimulating hormone (TSH) receptor autoantibodies as well as 21-hydroxylase antibodies were elevated. Conclusions Although the combination of Graves' and Addison's disease is extremely rare, especially in children, it is critical to make the diagnosis. Accelerated metabolic rate increased the risk for adrenal crises in our patient. This case contributes to the spectrum of APS II and its manifestation.


Advances in the role of silence information regulator family in pathological pregnancy.
Aberrant maternal inflammation and oxidative stress are the two main mechanisms of pathological pregnancy. The silence information regulator (sirtuin) family is a highly conserved family of nicotinamide adenine dinucleotide (NAD)-dependent deacylases. By regulating the post-translational modification of proteins, sirtuin is involved in various biological processes including oxidative stress and inflammation. Nowadays, emerging evidence indicates that sirtuin may be closely related to the occurrence and development of pathological pregnancy. The down-regulation of sirtuin can cause spontaneous preterm delivery by promoting uterine contraction and rupture of fetal membranes, cause gestational diabetes mellitus through promoting oxidative stress and affecting the activity of key enzymes in glucose metabolism, cause preeclampsia by reducing the proliferation and invasion ability of trophoblasts, cause intrahepatic cholestasis of pregnancy by promoting the production of bile acids and T helper 1 cell (Th1) cytokines, and cause intrauterine growth restriction through inducing mitochondrial dysfunction. Moreover, the expression and activation of sirtuin can be modulated through dietary interventions, thus sirtuin is expected to become a new target for the prevention and treatment of pregnancy complications. This article reviews the role of the sirtuin family in the occurrence and development of pathological pregnancy and its influence on the development of the offspring.


Coping with nosocomial infection: a non-antibiotic approach.
This article discusses the control of nosocomial infection using strategies other than antimicrobial therapy, based on the concepts of asepsis, disinfection and isolation of infectious patients. The aim is to prevent the spread of pathogenic organisms from patient to patient. Infection control techniques are practised in parallel with direct antibiotic therapy but should reduce the overall use of antibiotics, and reduce the selection pressure for organisms to develop resistance.


Secretion of primary urine by glomeruli of the hagfish kidney
Adrenaline and noradrenaline increased the perfusion pressure (Pperf) and single glomerulus filtration rate (SGFR) of perfused hagfish glomeruli. Small amounts (0.1 % or 0.5 %) of bovine serum albumin (BSA) in perfusion fluids containing Ficoll 70 did not diminish the loss of colloid from hagfish glomerular capillaries as has been reported for other perfused capillaries. However, replacement of Ficoll 70 with an osmotically equivalent amount (3 %) of BSA appreciably reduced colloid loss. It was concluded that adrenaline and colloids enhanced flow through the urine-forming capillaries. Whereas adrenaline elevated the SGFR, colloid lowered the SGFR probably by a direct effect on the fluid permeability of the capillary walls. The flow-enhancing effect of adrenaline was used to ensure the exposure of urine-forming capillaries to two inhibitors of active fluid transport, ouabain and 2,4-dinitrophenol (DNP). Both substances lowered the single glomerulus filtration fraction (SGFF), probably by affecting a fluid secretion mechanism. In addition, DNP diminished the flow-enhancing effect of adrenaline. This study provides relatively unequivocal evidence that fluid secretion underlies the formation of primary urine by the hagfish.


Infected granuloma and inclusion cyst secondary to a retained foreign body.
Foreign body granuloma formation and epidermal inclusion cyst formation are a common result of retained foreign bodies. The subsequent rupture of an inclusion cyst will result in abscess formation along with ulceration. The following is a review of pathology involved in granuloma formation, as well as a presentation of an interesting case involving granuloma formation secondary to a retained foreign body.


The Viscum album preparation Isorel inhibits the growth of melanoma B16F10 by influencing the tumour-host relationship.
The aim of this study was to analyse whether Viscum album (mistletoe; Isorel) modulates the tumour-host relationship and whether this might be a basic mechanism of the antitumorous activity of the drug. The effects of a single intraperitoneal injection of the drug (100 mg/kg single 'planta tota' dose) were analysed for mice-bearing melanoma B16F10 growing in the hind limb. Injection of Isorel reduced the size of the tumour and caused abundant tumour necrosis with inflammatory response, oedema and destruction of the malignant tissue. Furthermore, the lymphocytes of saline-treated tumorous mice were not able to respond to the mitogenic lectin concanavalin A in vitro, while those of mistletoe extract-treated mice showed high reactivity too the mitogen, but only if cultured in the medium supplemented with the plasma of the mistletoe extract-treated mice. Moreover, melanoma cells exposed to the mistletoe extract were more sensitive to the cytotoxic activity of the lymphocytes than the control tumour cells, particularly in the presence of the plasma of mistletoe extract-treated mice. The plasma itself, however, did not show any cytotoxic activity. These results indicate that the antitumour activity of the mistletoe drug is due to a modulation of the tumour-host relationship, mediated by direct cytotoxicity of the drug to tumour cells and/or through a potentiation of immune response by certain, as yet unidentified, growth modifying humoral factors of the host.


Early production of thymic stromal lymphopoietin precedes infiltration of dendritic cells expressing its receptor in allergen-induced late phase cutaneous responses in atopic subjects.
Thymic stromal lymphopoietin (TSLP) is an interleukin (IL)-7-like cytokine that triggers dendritic cell-mediated T helper (Th)2 inflammatory responses through a receptor consisting of a heterodimer of the IL-7 receptor alpha (IL-7Ralpha) chain and the TSLP receptor (TSLPR), which resembles the cytokine receptor common gamma chain. Dendritic cells activated by TSLP prime development of CD4(+) T cells into Th2 cells contributing to the pathogenesis of allergic inflammation. We hypothesized that allergen exposure induces expression of TSLP and results in recruitment of TSLPR bearing cells in the cutaneous allergen-induced late-phase reaction (LPR) in atopic subjects. Skin biopsies were obtained from atopic subjects (n = 9) at various times after cutaneous allergen challenge. In situ hybridization and immunohistochemistry were used to determine TSLP mRNA expression and to measure infiltration of TSLPR(+) DC in skin LPR. RT-PCR and flow cytometry were employed to analyse TSLPR expression on isolated blood DC. Allergen-induced skin TSLP expression occurred as early as 1 h after allergen challenge, whereas TSLPR(+) and CD11c(+) cells infiltrated relatively late (24-48 h). The majority of TSLPR(+) cells were DC co-expressing blood DC antigen-1 (BDCA-1) or BDCA-2. Freshly isolated blood DC expressed both TSLPR and IL-7Ralpha chains. Maturation and stimulation with TSLP or polyriboinosinic-polyribocytidylic acid in vitro upregulated the expression of both TSLPR and IL-7Ralpha chains in DC but not in chemoattractant receptor-homologous molecule expressed on Th2 cells(+) CD4(+) T cells. The data suggest that TSLP plays a role in augmenting, through DC recruitment and activation, the development of Th2-type T cells in allergic inflammation.


From the discovery of vascular endothelial growth factor to the introduction of avastin in clinical trials - an interview with Napoleone Ferrara by Domenico Ribatti.
Napoleone Ferrara and his colleagues at Genentech were the first to isolate and clone vascular endothelial growth factor (VEGF) in 1989. His laboratory has investigated many aspects of VEGF biochemistry and molecular biology. In 1993, Ferrara reported that inhibition of VEGF-induced angiogenesis by specific monoclonal antibodies resulted in dramatic suppression of the growth of a variety of tumors in vivo. These findings provided an important evidence that inhibition of angiogenesis may suppress tumor growth and blocking VEGF action could have therapeutic value for a variety of malignancies. A further development was the design in a rational fashion in 1997 of a humanized anti-VEGF monoclonal antibody (Avastin), now in clinical trials as a treatment for several solid tumors and also outside of cancer, in the treatment of age-related macular degeneration (AMD). Ferrara's work is revolutionizing quality of life for many of the estimated 1.2 million individuals in the US who have wet AMD. Upwards of a million AMD patients worldwide have already received anti-VEGF antibody therapy.


Differences in membrane fluidity and fatty acid composition between phenotypic variants of Streptococcus pneumoniae.
Phase variation in the colonial opacity of Streptococcus pneumoniae has been implicated as a factor in the pathogenesis of pneumococcal disease. This study examined the relationship between membrane characteristics and colony morphology in a few selected opaque-transparent couples of S. pneumoniae strains carrying different capsular types. Membrane fluidity was determined on the basis of intermolecular excimerization of pyrene and fluorescence polarization of 1,6-diphenyl 1,3,5-hexatriene (DPH). A significant decrease, 16 to 26% (P < or = 0.05), in the excimerization rate constant of the opaque variants compared with that of the transparent variants was observed, indicating higher microviscosity of the membrane of bacterial cells in the opaque variants. Liposomes prepared from phospholipids of the opaque phenotype showed an even greater decrease, 27 to 38% (P < or = 0.05), in the pyrene excimerization rate constant compared with that of liposomes prepared from phospholipids of bacteria with the transparent phenotype. These findings agree with the results obtained with DPH fluorescence anisotropy, which showed a 9 to 21% increase (P < or = 0.001) in the opaque variants compared with the transparent variants. Membrane fatty acid composition, determined by gas chromatography, revealed that the two variants carry the same types of fatty acids but in different proportions. The trend of modification points to the presence of a lower degree of unsaturated fatty acids in the opaque variants compared with their transparent counterparts. The data presented here show a distinct correlation between phase variation and membrane fluidity in S. pneumoniae. The changes in membrane fluidity most probably stem from the observed differences in fatty acid composition.


GATA2 germline mutations impair GATA2 transcription, causing haploinsufficiency: functional analysis of the p.Arg396Gln mutation.
Germline GATA2 mutations have been identified as the cause of familial syndromes with immunodeficiency and predisposition to myeloid malignancies. GATA2 mutations appear to cause loss of function of the mutated allele leading to haploinsufficiency; however, this postulate has not been experimentally validated as the basis of these syndromes. We hypothesized that mutations that are translated into abnormal proteins could affect the transcription of GATA2, triggering GATA2 deficiency. Chromatin immunoprecipitation and luciferase assays showed that the human GATA2 protein activates its own transcription through a specific region located at -2.4 kb, whereas the p.Thr354Met, p.Thr355del, and p.Arg396Gln germline mutations impair GATA2 promoter activation. Accordingly, GATA2 expression was decreased to ∼58% in a patient with p.Arg396Gln, compared with controls. p.Arg396Gln is the second most common mutation in these syndromes, and no previous functional analyses have been performed. We therefore analyzed p.Arg396Gln. Our data show that p.Arg396Gln is a loss-of-function mutation affecting DNA-binding ability and, as a consequence, it fails to maintain the immature characteristics of hematopoietic stem and progenitor cells, which could result in defects in this cell compartment. In conclusion, we show that human GATA2 binds to its own promoter, activating its transcription, and that the aforementioned mutations impair the transcription of GATA2. Our results indicate that they can affect other GATA2 target genes, which could partially explain the variability of symptoms in these diseases. Moreover, we show that p.Arg396Gln is a loss-of-function mutation, which is unable to retain the progenitor phenotype in cells where it is expressed.


Smartphone-based colorimetric detection systems for glucose monitoring in the diagnosis and management of diabetes.
Diabetes is a group of metabolic conditions resulting in high blood sugar levels over prolonged periods that affects hundreds of millions of patients worldwide. Measuring glucose concentration enables patient-specific insulin therapy, and is essential to reduce the severity of the disease, potential complications, and related mortalities. Recent advances and developments in smartphone-based colorimetric glucose detection systems are discussed in this review. The importance of glucose monitoring, data collection, transfer, and analysis, via non-invasive/invasive methods is highlighted. The review also presents various approaches using 3D-printed materials, screen-printed electrodes, polymer templates, designs allowing multiple glucose analysis, bioanalytes and/or nanostructures for glucose detection. The positive effects of advances in improving the performance of smartphone-based platforms are introduced along with future directions and trends in the application of emerging technologies in smartphone-based diagnostics.


Eosinophilic fasciitis secondary to intravenous iron infusions.
A 43-year-old African-American female with anemia secondary to uterine leiomyomas and menorrhagia presented with induration and stiffness of the right arm and hand four weeks after receiving intravenous iron infusions at multiple infusion sites along the right proximal forearm. Multiple intravenous sites between her right antecubital fossa and wrist had to be used because developing pain necessitated the site changes. The iron infusions were performed because the patient had refused blood transfusions and her symptoms failed to resolve on oral iron supplementation. The skin induration persisted and progressed for several months at which time a skin biopsy was performed. The skin histology was consistent with eosinophilic fasciitis and her complete blood count was notable for a peripheral eosinophilia. Because of the location of the fibrosis and the time proximity in relation to her infusions, a relationship between the iron infusions and eosinophilic fasciitis was made. Cutaneous fibrosis has been linked to immunologic dysfunction, autoantibody production, tissue hypoxia, and vascular damage, which may have been contributing factors in this patient. Eosinophilic fasciitis has been linked to certain drugs and chemicals, notably L-tryptophan ingestion and the statin family of drugs.


Automatic Sparse Connectivity Learning for Neural Networks.
Since sparse neural networks usually contain many zero weights, these unnecessary network connections can potentially be eliminated without degrading network performance. Therefore, well-designed sparse neural networks have the potential to significantly reduce the number of floating-point operations (FLOPs) and computational resources. In this work, we propose a new automatic pruning method-sparse connectivity learning (SCL). Specifically, a weight is reparameterized as an elementwise multiplication of a trainable weight variable and a binary mask. Thus, network connectivity is fully described by the binary mask, which is modulated by a unit step function. We theoretically prove the fundamental principle of using a straight-through estimator (STE) for network pruning. This principle is that the proxy gradients of STE should be positive, ensuring that mask variables converge at their minima. After finding Leaky ReLU, Softplus, and identity STEs can satisfy this principle, we propose to adopt identity STE in SCL for discrete mask relaxation. We find that mask gradients of different features are very unbalanced; hence, we propose to normalize mask gradients of each feature to optimize mask variable training. In order to automatically train sparse masks, we include the total number of network connections as a regularization term in our objective function. As SCL does not require pruning criteria or hyperparameters defined by designers for network layers, the network is explored in a larger hypothesis space to achieve optimized sparse connectivity for the best performance. SCL overcomes the limitations of existing automatic pruning methods. Experimental results demonstrate that SCL can automatically learn and select important network connections for various baseline network structures. Deep learning models trained by SCL outperform the state-of-the-art human-designed and automatic pruning methods in sparsity, accuracy, and FLOPs reduction.


Renal tubular injury induced by glyphosate combined with hard water: the role of cytosolic phospholipase A2.
The combined effects of glyphosate and hard water on chronic kidney disease of unknown etiology (CDKu) have attracted much interest, but the mechanisms remain unknown. Cytoplasmic phospholipase A2 (cPLA2) plays a key role in the acute and chronic inflammatory reactions. This study explored the effect of glyphosate combined with hard water on renal tubules and the possible targets and mechanisms involved. In vivo experiments were conducted to investigate the synergistic effects and potential mechanisms of glyphosate and hard water on renal tubular injury in mice. Administration of glyphosate in mice resulted in elevated levels of β2-microglobulin (β2-MG), albumin (ALB), and serum creatinine (SCr) compared to control mice. This increase was more pronounce when glyphosate was combined with hard water. In the glyphosate-treated mice, small areas of the kidney revealed fibroblast proliferation and vacuolar degeneration, particularly at the higher dose of 400 mg/kg glyphosate. However, the combination of glyphosate and hard water induced an even greater degree of pathological changes in the kidney. Immunofluorescence and western blot analyses showed that glyphosate and hard water had a coordinated effect on calcium ions (Ca2+)-activated phospholipase A2 and the activation may play a key role in inflammation and renal tubular injury. Exposure to glyphosate alone or glyphosate plus hard water increased the levels of oxidative stress markers and inflammatory biomarkers, namely, thromboxane A2 (TX-A2), leukotriene B4 (LTB4), prostaglandin E2 (PGE2), nitric oxide synthase (NOS), and nitric oxide (NO). Parameters of oxidative stress, including the levels of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were decreased. Further analysis showed that the levels of these biomarkers were significantly different between the mice treated with glyphosate plus hard water and the mice treated with glyphosate alone. These findings suggested that hard water combined with glyphosate can induce renal tubular injury in mice, and this may involve mitogen-activated protein kinases (MAPK)/cytosolic phospholipase A2 (cPLA2)/arachidonic acid (AA) and its downstream factors.


[Medical case of successful therapy of polymyositis by high doses of glucocorticoid].
Questions of diagnostics and treatment of dermatomyositis-polymyositis in literature are contradictory character. They have scanty description of peculiarities of course of this pathology by men of young and certain age, and character of complications, connected with long ingestion of corticosteroid agents. Medical case, done in the article, is of great interest undoubtedly. By reason of using corticosteroid agents, the patient get a complex of specific complications, but pains in muscles, fever, arthralgia, weakness have disappeared. There was made a decision about speeded decreasing of dose of hormonal agent to 8 mg per day for the term pf 3 months in alternative session with parallel ingestion of disaggregants. On this base was marked epilosis of bioptic damage, was achieved recanalization of deep viens of left leg, was normalized carbohydrate metabolism, generalclinic analyze of blood, transaminase level, body weight was decreased. Now-days it's marked a clinical-laboratorial remission, not requiring a supplying corticosteroid therapy.


Recommendations for the management of patients with systemic rheumatic diseases during the coronavirus disease pandemic.
Patients with systemic rheumatic diseases (SRD) are vulnerable for coronavirus disease (COVID-19). The Korean College of Rheumatology recognized the urgent need to develop recommendations for rheumatologists and other physicians to manage patients with SRD during the COVID-19 pandemic. The working group was organized and was responsible for selecting key health questions, searching and reviewing the available literature, and formulating statements. The appropriateness of the statements was evaluated by voting panels using the modified Delphi method. Four general principles and thirteen individual recommendations were finalized through expert consensus based on the available evidence. The recommendations included preventive measures against COVID-19, medicinal treatment for stable or active SRD patients without COVID-19, medicinal treatment for SRD patients with COVID-19, and patient evaluation and monitoring. Medicinal treatments were categorized according to the status with respect to both COVID-19 and SRD. These recommendations should serve as a reference for individualized treatment for patients with SRD. As new evidence is emerging, an immediate update will be required.


The role of distubances of phosphate metabolism in metabolic syndrome.
Metabolic syndrome represents a cluster of cardiovascular risk factors that has become a public health problem of epidemic proportions. It was proposed that disturbances in phosphate metabolism may represent a key feature of metabolic syndrome, with a high contribution of cardiovascular risk factors. The aim of the study is to investigate the relationship between phosphate levels and the presence of the characteristics of metabolic syndrome, as well as the mechanisms that may responsible for reduced phosphate levels in patients with metabolic syndrome. One hundred fifty five subjects are enrolled in the study: 64 with metabolic syndrome and 91 without this syndrome. Biochemical parameters of the metabolic syndrome study populations were compared with healthy population study. Patients with metabolic syndrome showed significantly lower phosphate (46%) and magnesium levels compared with controls (22.7%) (p<0.001).Because fractional excretion of phosphate was similar in both groups, we think that hypophosphatemia in patients with metabolic syndrome can be attributed to decreased dietary intake, as well as internal redistribution of this element. Lower magnesium hyperinsulimemia-induced renal magnesium wasting also may be a contributory factor. Patients with metabolic syndrome show significantly lower phosphate and magnesium concentrations compared with individuals who do not fulfill criteria for diagnosis of this syndrome. This reduction is likely to be attributed to reduced dietary intake and internal redistribution of phosphate and is more pronounced as the number of components of metabolic syndrome increases. The clinical significance of these disturbances, as well as their importance as targets for preventive or therapeutic interventions, remains to be established.


A Phosphite Dehydrogenase Variant with Promiscuous Access to Nicotinamide Cofactor Pools Sustains Fast Phosphite-Dependent Growth of Transplastomic Chlamydomonas reinhardtii.
Heterologous expression of the NAD+-dependent phosphite dehydrogenase (PTXD) bacterial enzyme from Pseudomonas stutzerii enables selective growth of transgenic organisms by using phosphite as sole phosphorous source. Combining phosphite fertilization with nuclear expression of the ptxD transgene was shown to be an alternative to herbicides in controlling weeds and contamination of algal cultures. Chloroplast expression of ptxD in Chlamydomonas reinhardtii was proposed as an environmentally friendly alternative to antibiotic resistance genes for plastid transformation. However, PTXD activity in the chloroplast is low, possibly due to the low NAD+/NADP+ ratio, limiting the efficiency of phosphite assimilation. We addressed the intrinsic constraints of the PTXD activity in the chloroplast and improved its catalytic efficiency in vivo via rational mutagenesis of key residues involved in cofactor binding. Transplastomic lines carrying a mutagenized PTXD version promiscuously used NADP+ and NAD+ for converting phosphite into phosphate and grew faster compared to those expressing the wild type protein. The modified PTXD enzyme also enabled faster and reproducible selection of transplastomic colonies by directly plating on phosphite-containing medium. These results allow using phosphite as selective agent for chloroplast transformation and for controlling biological contaminants when expressing heterologous proteins in algal chloroplasts, without compromising on culture performance.


Altered oral microbiota in chronic hepatitis B patients with different tongue coatings.
To elucidate tongue coating microbiota and metabolic differences in chronic hepatitis B (CHB) patients with yellow or white tongue coatings. Tongue coating samples were collected from 53 CHB patients (28 CHB yellow tongue coating patients and 25 CHB white tongue coating patients) and 22 healthy controls. Microbial DNA was extracted from the tongue samples, and the bacterial 16S ribosomal RNA gene V3 region was amplified from all samples and sequenced with the Ion Torrent PGM™ sequencing platform according to the standard protocols. The metabolites in the tongue coatings were evaluated using a liquid chromatography-mass spectrometry (LC-MS) platform. Statistical analyses were then performed. The relative compositions of the tongue coating microbiotas and metabolites in the CHB patients were significantly different from those of the healthy controls, but the tongue coating microbiota abundances and diversity levels were not significantly different. Compared with the CHB white tongue coating patients, the CHB yellow tongue coating patients had higher hepatitis B viral DNA (HBV-DNA) titers (median 21210 vs 500, respectively, P = 0.03) and a significantly lower level of Bacteroidetes (20.14% vs 27.93%, respectively, P = 0.013) and higher level of Proteobacteria (25.99% vs 18.17%, respectively, P = 0.045) in the microbial compositions at the phylum level. The inferred metagenomic pathways enriched in the CHB yellow tongue coating patients were mainly those involved in amino acid metabolism, which was consistent with the metabolic disorder. The abundances of bacteria from Bacteroidales at the order level were higher in the CHB white tongue coating patients (19.2% vs 27.22%, respectively, P = 0.011), whereas Neisseriales were enriched in the yellow tongue coating patients (21.85% vs 13.83%, respectively, P = 0.029). At the family level, the abundance of Neisseriaceae in the yellow tongue patients was positively correlated with the HBV-DNA level but negatively correlated with the S-adenosyl-L-methionine level. This research illustrates specific clinical features and bacterial structures in CHB patients with different tongue coatings, which facilitates understanding of the traditional tongue diagnosis.


R-factor transfer in selenite and tetrathionate broths.
After overnight incubation of R(+)Escherichia coli with R(-)Salmonella typhimurium in selenite and tetrathionate with Brilliant Green (TBG) broths, R-factor transfer was demonstrated in 10 of 12 experiments. R-factor transfer in these enrichment broths occurred at a markedly reduced frequency in comparison to that in Trypticase soy broth, apparently due to an adverse effect either on the viability of the donor E. coli or the conjugation process itself. Transfer of R factors in commonly used enrichment broths may give rise to falsely resistant antibiotic patterns in Salmonella. However, the frequency of R-factor transfer is so low that it is unlikely to affect significantly the interpretation of R-factor studies.


Outcomes assessment in men undergoing open retropubic radical prostatectomy, laparoscopic radical prostatectomy, and robotic-assisted radical prostatectomy.
To review the various methods of outcomes assessment used for effectiveness studies comparing retropubic radical prostatectomy (RRP), laparoscopic radical prostatectomy (LRP), and robotic-assisted laparoscopic prostatectomy (RALP). A review of the peer reviewed literature was performed for reported series of RRP, LRP, and RALP using Pubmed and MEDLINE with emphasis on comparing perioperative, functional, and oncologic outcomes. Common methods used for outcomes assessment were categorized and compared, highlighting the pros and cons of each approach. The majority of the literature comparing RRP, LRP, and RALP comes in the form of observational data or administrative data from secondary datasets. While randomized controlled trials are ideal for outcomes assessment, only one such study was identified and was limited. Non-randomized observational studies contribute to the majority of data, however are limited due to retrospective study design, lack of consistent endpoints, and limited application to the general community. Administrative data provide accurate assessment of operative outcomes in both academic and community settings, however has limited ability to convey accurate functional outcomes. Non-randomized observational studies and secondary data are useful resources for assessment of outcomes; however, limitations exist for both. Neither is without flaws, and conclusions drawn from either should be viewed with caution. Until standardized prospective comparative analyses of RRP, LRP, and RALP are established, comparative outcomes data will remain imperfect. Urologic researchers must strive to provide the best available outcomes data through accurate prospective data collection and consistent outcomes reporting.


Ubiquinone biosynthesis in Escherichia coli K-12. Accumulation of an octaprenol, farnesylfarnesylgeraniol, by a multiple aromatic auxotroph.
Cell extracts of a multiple aromatic auxotroph of Escherichia coli K-12, strain AB2830, grown in the absence of precursors of the quinone rings of the ubiquinone and menaquinone molecules, converted 4-hydroxy[U-(14)C]benzoate into a mixture of 3-octaprenyl-4-hydroxybenzoate and 2-octaprenylphenol. An octaprenol, farnesylfarnesylgeraniol, was isolated from such cell extracts and characterized by n.m.r. and mass spectroscopy. Neither the octaprenol, nor polyprenylation of 4-hydroxy[U-(14)C]benzoate, could be detected in cell extracts of strain AB2830 grown in the presence of 0.1mm-4-hydroxybenzoate. It was concluded that, in the biosynthesis of ubiquinone, the polyprenyl side chain is added to 4-hydroxybenzoate as a C(40) unit, the active form of which is converted by cell extracts into farnesylfarnesylgeraniol. The multiple aromatic auxotroph, when grown in the absence of 4-hydroxybenzoate but in the presence of 4-aminobenzoate, converted the latter compound into 3-octaprenyl-4-aminobenzoate. This compound was isolated from whole cells and characterized by n.m.r. and mass spectroscopy.