Impact of COVID-19 on healthcare system in India: A systematic review.
Despite an extensive healthcare system in India, the COVID-19 Pandemic created havoc upon the existing Indian healthcare system by disrupting the supply of essential healthcare services to patients. It has also highlighted the significant-quality discrepancies of healthcare facilities between the rural-urban areas and between public and private healthcare providers. The not so advanced healthcare system of India was exposed through the lack of oxygen and essential drugs required for the treatment of COVID-19. Additionally, during the pandemic period there was a drastic decline in seeking non-COVID-19 disease related healthcare services. The objective of this systematic review is to determine whether COVID-19 has impacted the healthcare system in India.


Nursing assessment and care of children with atopic eczema.
Atopic eczema is an increasingly common childhood condition that can be very troublesome for both the child and his or her carers. Education, advice, support and an individual treatment plan are very important for both patient and carer, and these services are largely provided by nurses in the community, often within skin disease management clinics.


Influence of weight-bearing exercises on bone acquisition in prepubertal monozygotic female twins: a randomized controlled prospective study.
The aim of this study was to determine whether high-impact exercises have an osteogenic effect in 21 prepubertal female monozygotic twins aged 8.7 (SD 0.7) years. Bone mineral density (aBMD), bone mineral content (BMC), bone area, and body composition were derived from DXA. Skeletal maturity was assessed by the Tanner-Whitehouse technique. Anthropometric dimensions (28 dimensions) were measured and also used to derive adiposity and muscularity indices, and information about physical activity was obtained by questionnaire. These measurements were taken before and after the exercise period. The exercise program consisted of high-impact exercises. During 9 months, one girl of each twin pair performed the exercises 3 times a week under supervision of a teacher while their sisters served as control group. At baseline there were no differences between the groups. After 9 months, exercisers (Ex) and controls (Con) had similar increases in height and weight. Significant lower adiposity was observed in the exercise group vs the control group. None of the bone indices differed significantly between the two groups. When the analyses were done for a subgroup of twin pairs (n = 12) who did not participate in high-impact sports during their leisure time, significant differences were obtained for aBMD and BMC of the proximal femur in favor of the exercise group. These results indicate that for prepubertal girls who are not involved in sport activities or who are only involved in low-impact sport activities this exercise program has an osteogenic effect on the proximal femur, but for girls who are already involved in high-impact sports this protocol does not have any additional effect on the bone status.


Wilms' tumor: a 10 year retrospective study.
Wilms' tumor (nephroblastoma) is the most common renal malignancy of childhood. The aim of the study was to evaluate the characteristics of Wilms' tumor and the results of combined modality treatment obtained in our center in Tehran. Fifty-five patients diagnosed as having Wilms' tumor were studied in the period between February 1992 and March 2002. Demographic features, mode of presentation, associated anomalies, the stage of tumor, histopathologic results, and the survival rates were evaluated. Of these 55 patients, 31 were males and 24 were females (M/F = 1.2). The mean age at the time of diagnosis was 45.2 months. The distribution of 54 operated patients according to the surgical stage was: stage I 32.7%, stage II 16.36%, stage III 38.1%, stage IV 9%, and stage V 1.8% (one patient (1.8%) has not been operated). Favorable histology was diagnosed in 54.5% and unfavorable histology in 43.6% of the patients. The patients were treated according to National Wilms' Tumor Study protocols. The relapse-free and overall 4 years survival rates were 71% and 86%, respectively. As a developing country, with similar relapse free and overall survival rates to National Wilms' Tumor Study, our institution showed an improvement in the treatment of patients with Wilms' tumor in recent 10 years, but with more adaptation to the National Wilms' Tumor Study treatment protocols better optimum results seem to be achievable.


Varying efficacy of superdisintegrants in orally disintegrating tablets among different manufacturers.
The main objective of the present study was to develop an orally disintegrating tablet formulation of domperidone and to study the functionality differences of superdisintegrants each obtained from two different sources on the tablet properties. Domperidone tablets were formulated with different superdisintegrants by direct compression. The effect of the type of superdisintegrant, its concentration and source was studied by measuring the in-vitro disintegration time, wetting time, water absorption ratios, drug release by dissolution and in-vivo oral disintegration time. Tablets prepared with crospovidone had lower disintegration times than tablets prepared from sodium starchglycolate and croscarmellose sodium. Formulations prepared with Polyplasdone XL, Ac-Di-Sol, and Explotab (D series) were better than formulations prepared with superdisintegrants obtained from other sources (DL series) which had longer disintegration times and lower water uptake ratios. The in-vivo disintegration time of formulation D-106 containing polyplasdone XL was significantly lower than that of the marketed formulation Domel-MT. The results from this study suggest that disintegration of orally disintegrating tablets is dependent on the nature of superdisintegrant, concentration in the formulation and its source. Even though a superdisintegrant meets USP standards there can be a variance among manufacturers in terms of performance. This is not only limited to in-vitro studies but carries over to disintegration times in the human population.


Coadministration of ornithine and alpha-ketoglutarate is no more effective than ornithine alone as an arginine precursor in piglets enterally fed an arginine-deficient diet.
Simultaneous administration of alpha-ketoglutarate and ornithine, in a 1:2 molar ratio, may improve the effectiveness of ornithine as an arginine precursor in neonatal piglets by shifting ornithine metabolism away from oxidation and toward the synthesis of arginine and other metabolically important compounds. To study this proposed mechanism, enterally fed piglets were allocated to receive 1 of 4 diets for 5 d: an arginine-deficient [1.2 mmol/(kg . d) arginine] diet (basal), or the basal diet supplemented with either alpha-ketoglutarate [4.6 mmol/(kg x d)] (+alpha-KG), ornithine [9.2 mmol/(kg x d)] (+Orn), or both ornithine and alpha-ketoglutarate (+alpha-KG/+Orn, molar ratio 1:2). Primed, constant infusions of [1-(14)C]ornithine given both intragastrically and intraportally were used to measure ornithine kinetics and determine the role of first-pass intestinal metabolism in ornithine metabolism. Whole body arginine and glutamate kinetics were measured using a primed, constant intragastric infusion of [guanido-(14)C]arginine and [3,4-(3)H]glutamate. The diets did not affect plasma arginine or ammonia concentrations, arginine flux, or arginine synthesis from ornithine. Therefore, arginine synthesis was not increased by the simultaneous infusion of ornithine and alpha-ketoglutarate. Piglets that received dietary ornithine had a 2-fold greater rate of proline synthesis from ornithine (P < 0.05) and oxidized a greater (P < 0.05) portion of the infused ornithine than piglets in the basal and +alpha-KG groups. Overall, ornithine addition to an arginine deficient diet had a greater effect on ornithine and arginine metabolism than the addition of alpha-ketoglutarate. First-pass intestinal metabolism was critical for ornithine synthesis and conversion to other metabolites but not for ornithine oxidation.


Surgical treatment of elderly patients with severe aortic stenosis in the modern era - review.
Surgical treatment of severe aortic stenosis offers good early and long-term results, even in elderly patients. Despite the implementation of percutaneous methods for the very high-risk group, surgical valve replacement remains the gold standard. The advanced age of patients should not be the only indicator limiting the possibility of surgery. In this review we present the most important information on the results of aortic stenosis surgical treatment in the groups of older patients. New methods such as percutaneous and minimally invasive methods of surgery are also discussed. Additionally, the presented information is referred to current guidelines for the treatment of severe aortic stenosis.


Hearing loss among high school farm students.
To study the prevalence of hearing loss among teen-aged farm children in central Wisconsin, audiometric threshold testing of 872 vocational agriculture students was carried out over a three-year period. The results indicate an increased prevalence of hearing loss among students actively involved in farm work, as compared to their peers not involved in farm work. Findings also suggest that use of hearing protection may reduce the risk of hearing loss among students who work on the farm, although few students report the use of such devices. These data also suggest that the hearing loss often observed in adult farmers may begin in childhood.


DNA Methylation Signatures in Vaginal Fluid Samples for Detection of Cervical and Endometrial Cancer.
A noninvasive tool that allows individuals to be monitored who are at risk of developing a malignancy is an unmet need. Such a test would need to consist of a molecular signature that allows for gradual judgment to assess the efficacy of preventive strategies. Here we performed a proof-of-principle study to test whether a DNA methylation (DNAme) signature in fluid collected from the vagina is able to identify women with cervical or endometrial cancer. DNA from vaginal fluid samples from 111 women (30, 8, 73 with endometrial cancer, cervical cancer, and benign gynecological conditions, respectively) were analyzed for DNAme using the Illumina 450k DNA methylation bead array assay, which allows the assessment of DNAme at more than 480.000 CpG sites. We developed a cervical and an endometrial cancer DNAme signature by comparing normal and cancerous cervical and endometrial samples from the publicly available The Cancer Genome Atlas data and developed deviation scores to assess the potential of discriminating cancer from a control sample using a vaginal fluid DNAme signature. More than 60% of variations in DNAme in our vaginal fluid cannot be explained by those clinical or technical factors that we were aware of. Both the cervical and the endometrial cancer DNAme signature resulted in receiver operating characteristic area under the curve between 0.75 and 0.83 to discriminate controls and the cancers for which the signature has been designed for. Whole DNAme signatures based on array technologies in body fluids are able to discriminate cancer cases from controls.


Alpha 1-adrenergic receptor-mediated phosphoinositide hydrolysis and prostaglandin E2 formation in Madin-Darby canine kidney cells. Possible parallel activation of phospholipase C and phospholipase A2.
alpha 1-Adrenergic receptors mediate two effects on phospholipid metabolism in Madin-Darby canine kidney (MDCK-D1) cells: hydrolysis of phosphoinositides and arachidonic acid release with generation of prostaglandin E2 (PGE2). The similarity in concentration dependence for the agonist (-)-epinephrine in eliciting these two responses implies that they are mediated by a single population of alpha 1-adrenergic receptors. However, we find that the kinetics of the two responses are quite different, PGE2 production occurring more rapidly and transiently than the hydrolysis of phosphoinositides. The antibiotic neomycin selectively decreases alpha 1-receptor-mediated phosphatidylinositol 4,5-bisphosphate hydrolysis without decreasing alpha 1-receptor-mediated arachidonic acid release and PGE2 generation. In addition, receptor-mediated inositol trisphosphate formation is independent of extracellular calcium, whereas release of labeled arachidonic acid is largely calcium-dependent. Moreover, based on studies obtained with labeled arachidonic acid, receptor-mediated generation of arachidonic acid cannot be accounted for by breakdown of phosphatidylinositol monophosphate, phosphatidylinositol bisphosphate, or phosphatidic acid. Further studies indicate that epinephrine produces changes in formation or turnover of several classes of membrane phospholipids in MDCK cells. We conclude that alpha 1-adrenergic receptors in MDCK cells appear to regulate phospholipid metabolism by the parallel activation of phospholipase C and phospholipase A2. This parallel activation of phospholipases contrasts with models described in other systems which imply sequential activation of phospholipase C and diacylglycerol lipase or phospholipase A2.


Colocalization of coilin and nucleolar proteins in Cajal body-like structures of micronucleated PtK2 cells.
Cajal bodies (CB) are ubiquitous nuclear structures involved in the biogenesis of small nuclear ribonucleoproteins and show narrow association with the nucleolus. To identify possible relationships between CB and the nucleolus, the localization of coilin, a marker of CB, and of a set of nucleolar proteins was investigated in cultured PtK2 cells undergoing micronucleation. Nocodazol-induced micronucleated cells were examined by double indirect immunofluorescence with antibodies against coilin, fibrillarin, NOR-90/hUBF, RNA polymerase I, PM/Scl, and To/Th. Cells were imaged on a BioRad 1024-UV confocal system attached to a Zeiss Axiovert 100 microscope. Since PtK2 cells possess only one nucleolus organizer region, micronucleated cells presented only one or two micronuclei containing nucleolus. By confocal microscopy we showed that in most micronuclei lacking a typical nucleolus a variable number of round structures were stained by antibodies against fibrillarin, NOR-90/hUBF protein, and coilin. These bodies were regarded as CB-like structures and were not stained by anti-PM/Scl and anti-To/Th antibodies. Anti-RNA polymerase I antibodies also reacted with CB-like structures in some micronuclei lacking nucleolus. The demonstration that a set of proteins involved in RNA/RNP biogenesis, namely coilin, fibrillarin, NOR-90/hUBF, and RNA polymerase I gather in CB-like structures present in nucleoli-devoid micronuclei may contribute to shed some light into the understanding of CB function.


Stress-induced release of substance P in the locus coeruleus modulates cortical noradrenaline release.
Several lines of evidence implicate the neuropeptide substance P (SP) in the modulation of emotional behavior. Interaction between SP and noradrenergic systems has been proposed to be important in the regulation of stress, depression, and anxiety mechanisms; however, most evidence so far is based on studies in unchallenged and/or anesthetized animals. Thus, by using a dual-probe microdialysis approach in freely moving animals, the aim of the present study was to investigate whether a relevant stressor can trigger the release of SP in the locus coeruleus (LC) and whether and how this response modulates noradrenaline (NA) transmission both in the LC and in the medial prefrontal cortex (mPFC), an important LC terminal region involved in emotional processing. While confirming previous reports that neurokinin 1 receptor (NK1R) antagonists activate cortical noradrenergic transmission under resting conditions, we present evidence that this interaction is opposite during stress challenge. Our results show that exposure to forced swimming considerably enhanced the release of SP and NA in the LC. Administration of a selective NK1R antagonist into the LC potentiated this NA response within the LC but abolished the stress-induced increase in NA release within the mPFC. These findings demonstrate stress-induced increase in endogenous extracellular SP levels within the LC exerting a facilitatory effect on the noradrenergic pathway to the mPFC. The attenuation of stress-induced hyperactivation of this pathway by NK1R antagonists, presumably via enhancing NA and autoinhibition in the LC, may contribute to the therapeutic efficacy of these drugs known to ameliorate symptoms of stress-related disorders.


Tris(3,5-dimethyl-1H-pyrazole-1-thiocarboxamidato-kappa(2)N(2),N)cobalt(III).
In the crystal structure of the title complex, [Co(C(6)H(8)N(3)S)(3)], the Co(III) atom is octahedrally coordinated by three monodeprotonated bidentate 3,5-dimethyl-1H-pyrazole-1-thiocarboxamide ligands with two thiocarboxamide N atoms in axial positions. The asymmetric unit contains two molecules (A and B) and these molecules are arranged in chains in an alternating fashion connected by N-H...S interactions.


Dynamic Changes of Ocular Surface in First-Time Contact Lens Wearers and the Effective Factors of Contact Lens Discomfort.
The purpose of the study is to investigate the dynamic changes in ocular surface indicators in first-time contact lens (CL) wearers and identify the most influential factors in CL discomfort (CLD). A total of 26 healthy non-CL wearers (26 eyes) were recruited and fitted monthly with disposable hydrogel CLs. Each participant underwent a full ocular surface evaluation, which include Efron grading, tear film breakup time, Schirmer's I test, corneal dendritic cell (DCs) imaging by in vivo confocal microscopy (IVCM), and conjunctival microvasculature evaluation by functional slit-lamp biomicroscopy. CLD was assessed using the Ocular Surface Disease Index questionnaire at baseline, 1 week, 1, 3, and 6 months after wearing it and another 6 months after discontinuing it. Clinical signs and CLD were significantly increased in the first week (p < 0.05). The microvascular response and DC activation peaked at the 1-month interval (p < 0.05). During CL wear, CLD is positively correlated with corneal staining (B = 0.238, p = 0.002), papillary conjunctivitis (B = 0.245, p < 0.001), and microvascular blood flow velocity (B = 0.353, p < 0.001). After discontinuation, only DC activation remained elevated at 6 months, whereas the other signs recovered. The first week of CL wear was the main period for the appearance of ocular surface clinical signs, and the first month was the main period for the activation of subclinical inflammation. Corneal staining and conjunctival microvascular response are the main factors affecting CLD. Even if the clinical signs recover after discontinuing wear, subclinical inflammation may persist.


A survey of study habits of general surgery residents.
To understand the study habits of general surgery residents as well as their motivating factors for study. A survey was mailed to general surgical residents. Performance on the American Board of Surgery In-Training Examination (ABSITE) was correlated with reported study habits using the Pearson's correlation coefficient. Massachusetts General Hospital and Brigham and Women's Hospital, 2 urban tertiary referral academic training institutions in Boston, Massachusetts. Fifty-eight general surgical residents of all training levels (including research). On average, surgical residents studied for 3 ± 1 days per week, the average duration of each study session being 1.3 ± 0.6 hours. The average total number of study hours per week was 3.4 ± 2.3. There were strong positive correlations between increased study frequency and high overall ABSITE score (Pearson's r = 0.339; p = 0.02) and between the total number of study hours per week and high overall ABSITE score (Pearson's r = 0.423; p < 0.005). Only 10% and 3% reported complete satisfaction with current study materials and routine, respectively. Most residents (96%) reported a willingness to try a new type of study method and 75% were willing to enroll in a trial comparing study methods. Increased study frequency and overall increased study duration are positively correlated with ABSITE performance. Dissatisfaction with current study materials and study routine is high, as is willingness to adopt new methods and enroll in investigational trials comparing study methods.


Effects of L-thyroxine treatment on heart functions in infants with congenital hypothyroidism.
Impaired heart functions in newborns with hypothyroidism should be reversed by levothyroxine substitution therapy. The aim of the study was to investigate heart functions with congenital hypothroidism (CH) in newborns and changes after levothyroxine substitution therapy, measured with tissue Doppler echocardiography and conventional echocardiography. The study included 30 neonates with CH and 34 healthy controls. Echocardiography were performed at baseline, 2nd week and 6th month of therapy. Heart systolic function was normal. Mitral E velocities and mitral E/A ratios were significantly lower in patients at baseline. Tei indices were significantly higher in patients and a significant negative correlation was detected between free thyroxine levels and Tei indices.When early and late post-treatment echocardiography findings are compared, a non-significant difference was detected. Neonates with CH may exhibit systolic and diastolic heart dysfunction, which can be reversed by early L-T4 substitution treatment. The Tei index index should be measured in addition to conventional echocardiography.


The effect of a 10-week high-intensity interval training and ginger consumption on inflammatory indices contributing to atherosclerosis in overweight women.
Most of the cardiovascular diseases can be prevented by doing regular physical exercises and using herbal supplements. The present study is aimed at assessing ginger supplement and high-intensity interval training (HIIT) on inflammatory indices contributing to atherosclerosis in overweight women. The present study is a randomized, experimental, and controlled one in which thirty healthy overweight women aged 20-30 years were randomly divided into three equal groups, namely, ginger, ginger + HIIT, and placebo + HIIT. The training groups performed high-intensity interval exercises (i.e. 40-m maximal shuttle run) for ten consecutive weeks. The supplement groups daily took 3 g of ginger pills and the third group took placebo. Paired t-test revealed a significant decrease in the density of type 1 monocytes chemo tactic protein (MCP-1) in HIIT + ginger (P = 0.026) and HIIT + placebo (P = 0.001) groups. Besides, maximum aerobic capacity in the two training groups significantly increased P = 0.002 and P = 0.000, respectively. In spite of this, analysis of variance showed no significant differences in three groups regarding the three indices such as intercellular adhesion molecule-1 (ICAM-1) (P = 0.093), MCP-1(P = 0.075), and serum interleukin-10 (IL-10) (P = 0.164). A 10-week intensive interval exercise, by itself or together with ginger supplement, improved MCP-1 and maximum oxygen consumption in overweight women, without any significant effect on soluble ICAM-1 and IL-10. These findings indicate the relative and efficient role of HIIT in overweight women without the necessity to combine with ginger as an antioxidant/anti-inflammatory supplement.


Acromioclavicular joint tuberculosis: apropos of two cases.
Tuberculosis is a great masquerader presenting in varied forms and in atypical locations. The myriad presentations of tuberculosis may complicate its diagnosis. We present two cases of acromioclavicular joint tuberculosis treated with a regimen of antitubercular drugs for 18 months leading to a complete resolution of symptoms.


Is distal forearm fracture in men due to osteoporosis?
Although widely regarded as a disease of women, osteoporosis does cause considerable morbidity and mortality in men. The lifetime risk of an osteoporortic fracture for a man is 1 in 12 and 30% of all hip fractures occur in men. In women, low-trauma distal forearm fracture is widely regarded as a typical early manifestation of postmenopausal osteoporosis. Traditionally, this has not been thought to be the case for men. We present a case-control study of 147 men with distal forearm fracture compared with 198 age-matched controls. The controls were selected from a pre-existing database of dual-energy X-ray absorptiometry scans of healthy volunteers. Both groups were sent questionnaires regarding basic demographics, fracture history and risk factors for osteoporosis, and the fracture group was asked to attend for bone densitometry. There were 103 responses from the fracture group (70%), of whom 67 (47%) underwent densitometry. There were 165 (83%) responses from the control group. Secondary causes of osteoporosis could be identified in 51% of the fracture group and 37% of the control group. The fracture group had significantly lower bone mineral density at all sites measured compared with the controls (0.75 g/cm(2) vs 0.85 g/cm(2) at the femoral neck, p<0.0001; 0.95 g/cm(2) vs 1.03 g/cm(2) at the total femur, p = 0.001; and 0.99 g/cm(2) vs 1.06 g/cm(2) at the lumbar spine, p = 0.001). These differences remained after adjusting for age and body mass index ( p<0.0005 at all sites). Overall, 41.8% of the fracture group were osteoporotic in at least one site ( T-score <-2.5 SD below the mean for young men) compared with only 10.3% of controls. This study is the first to demonstrate that men with distal forearm fractures have lower bone mineral density than their peers and a higher risk of osteoporosis.


Evanescent wave cavity ring-down spectroscopy in a thin-layer electrochemical cell.
The application of evanescent wave cavity ring-down spectroscopy (EW-CRDS) in monitoring electrogenerated species within a thin-layer electrochemical cell is demonstrated. In the proof-of-concept experiments described, ferricyanide, Fe(CN)6(3-), was produced by the transport-limited oxidation of ferrocyanide, Fe(CN)6(4-), in a thin-layer solution cell (25-250 microm) formed between an electrode and the hypotenuse of a fused-silica prism. The prism constituted one element of a high-finesse optical cavity arranged in a triangular ring geometry with light being totally internally reflected at the silica/solution interface. The cavity was pumped with the output (approximately 417 nm) of a single-mode external cavity diode laser, which was continuously scanned across the cavity modes. The presence of electrogenerated ferricyanide within the resulting evanescent field, beyond the optical interface, was detected by the enhanced loss of light trapped within the cavity, as measured by the characteristic cavity ring down. In this way, the EW-CRDS technique is sensitive to absorption in only the first few hundred nanometers of solution above the silica surface. The cavity ring-down response accompanying both cyclic voltammetric and step potential chronoamperometry experiments at a variety of electrode-surface distances is presented, and the results are shown to be well reproduced in modeling by finite element methods. The studies herein thus provide a foundation for further applications of EW-CRDS combined with electrochemistry.


A longitudinal study of verotoxin-producing Escherichia coli in two dairy goat herds.
A longitudinal study was conducted on two dairy farms to investigate the pattern of shedding of verotoxin-producing Escherichia coli (VTEC) in goats. Faecal samples were taken from 20 goat kids once weekly during the first 4 weeks of life and then once every month for the next 5 months of life, and from 18 replacement animals and 15 adults once every month for 12 months. The proportion of samples containing VTEC was higher for replacement animals and adults (85.7% and 78.7%, respectively) than for goat kids (25.4%). About 90% of the VTEC colonies isolated from healthy goats belonged to five serogroups (O33, O76, O126, O146 and O166) but the most frequent serogroups of these isolates, except one, were different in the two herds studied. E. coli O157:H7 was found in three goat kids on only one occasion. None of the VTEC isolates, except the three E. coli O157:H7 isolates, was eae-positive. The patterns of shedding of VTEC in goat kids were variable, but, in contrast, most of the replacement animals and adults were persistent VTEC shedders. Our results show that isolates of VTEC O33, O76, O126, O146 and O166 are adapted for colonising the intestine of goats but that, in contrast, infection with VTEC O157:H7 in goats seems to be transient.


Use of modafinil in spastic cerebral palsy.
After an initial patient with cerebral palsy had an apparent dramatic reduction in spasticity when placed on modafinil, a pilot study was undertaken in 10 pediatric patients to confirm or refute the benefit of modafinil in cerebral palsy. Nine of 10 patients completed the 1-month treatment period. The study patients were treated with 50 or 100 mg of modafinil once daily in the morning. An assessment was made at baseline and at 1 month on treatment. All patients had a clinical examination, Modified Ashworth Scale scores (spasticity) determined by a physical therapist, and videotaping of ambulation. In comparing visit 1 (baseline) and visit 2 (on treatment), statistically significant improvement in the modified Ashworth Scale scores was noted in seven of the nine patients completing the study (P = .0080). A blinded review of the videotapes did not show statistically significant differences in ambulation, but the speed (ft/sec) of gait improved in six of the nine patients (P = .0192). In this study, modafinil, a newly released central stimulant for narcolepsy, showed benefit in treating spasticity in patients with cerebral palsy. A second larger, placebo-controlled, double-blinded trial is planned to confirm these initial results and observations. Modafinil appears to benefit spastic cerebral palsy by a yet to be determined mechanism; however, a primary effect of modafinil on brainstem structures is hypothesized to reduce spasticity of central origin.


The secondary contact zone of phylogenetic lineages of the Philaenus spumarius (Hemiptera: Aphrophoridae): an example of incomplete allopatric speciation.
Previous studies on the phylogeography of the meadow spittlebug Philaenus spumarius (L.) (Hemiptera: Aphrophoridae) suggest the existence of a contact zone of its main phylogenetic lineages along mountain chains in Europe and western Asia. This study presents a detailed examination of the population genetics of P. spumarius within the Carpathian Mountains. The main objective was to determine whether the populations inhabiting that area consist of individuals belonging to different genetic units and whether the observed pattern could be an example of secondary contact zone which formed after incomplete allopatric speciation. Specimens from six transects across the Carpathian arc were examined. The mitochondrial phylogeography of the meadow spittlebug in the examined area clearly shows that individuals from both main clades meet and mix there. Representatives of all three main EF1-α clades were also found. The present distribution of the main clades with a zone of overlap along the mountain ranges may suggest that these phylogenetic lineages form a young hybrid zone. Moreover, a limited number of individuals were shown to possess heteroplasmic mitochondrial DNA, which gives additional support to intraspecific hybridization. P. spumarius could be used in future work as an excellent model species in investigating population genetics, intraspecific hybridization, and speciation in progress.


Q-Learning Based Fair and Efficient Coexistence of LTE in Unlicensed Band.
The increased demand for spectrum resources for multimedia communications and a limited licensed spectrum have led to widespread concern regarding the operation of long term evolution (LTE) in the unlicensed (LTE-U) band for internet of things (IoT) systems. Because Wi-Fi and LTE are diverse with dissimilar physical and link layer configurations, several solutions to achieve an efficient and fair coexistence have been proposed. Most of the proposed solutions facilitate a fair coexistence through a discontinuous transmission using a duty cycling or contention mechanism and an efficient coexistence through a clean channel selection. However, they are constrained only by fairness or efficient coexistence but not both. Herein, we propose joint adaptive duty cycling (ADC) and dynamic channel switch (DCS) mechanisms. The ADC mechanism supports a fair channel access opportunity by muting certain numbers of subframes for Wi-Fi users whereas the DCS mechanism offers more access opportunities for LTE-U and Wi-Fi users by preventing LTE-U users from occupying a crowded channel for a longer time. To support these mechanisms in a dynamic environment, LTE-U for IoT applications is enhanced using Q-learning techniques for an automatic selection of the appropriate combination of muting period and channel. Simulation results show the fair and efficient coexistence achieved from using the proposed mechanism.


External beam accelerated partial breast irradiation: dosimetric assessment of conformal and three different intensity modulated techniques.
Background The aim of the study was to evaluate and compare four different external beam radiotherapy techniques of accelerated partial breast irradiation (APBI) considering target coverage, dose to organs at risk and overall plan quality. The investigated techniques were three dimensional conformal radiotherapy (3D-CRT), "step and shoot" (SS) and "sliding window" (SW) intensity-modulated radiotherapy (IMRT), intensity-modulated arc therapy (RA). Patients and methods CT scans of 40 APBI patients were selected for the study. The planning objectives were set up according to the international recommendations. Homogeneity, conformity and plan quality indices were calculated from volumetric and dosimetric parameters of target volumes and organs at risk. The total monitor units and feasibility were also investigated. Results There were no significant differences in the coverage of the target volume between the techniques. The homogeneity indices of 3D-CRT, SS, SW and RA plans were 0.068, 0.074, 0.058 and 0.081, respectively. The conformation numbers were 0.60, 0.80, 0.82 and 0.89, respectively. The V50% values of the ipsilateral breast for 3D-CRT, SS, SW and RA were 47.5%, 40.2%, 39.9% and 31.6%, respectively. The average V10% and V40% values of ipsilateral lung were 13.1%, 28.1%, 28%, 36% and 2.6%, 1.9%, 1.9%, 3%, respectively. The 3D-CRT technique provided the best heart protection, especially in the low dose region. All contralateral organs received low doses. The SW technique achieved the best plan quality index (PQI). Conclusions Good target volume coverage and tolerable dose to the organs at risk are achievable with all four techniques. Taking into account all aspects, we recommend the SW IMRT technique for APBI.


The Suramin Derivative NF449 Interacts with the 5-fold Vertex of the Enterovirus A71 Capsid to Prevent Virus Attachment to PSGL-1 and Heparan Sulfate.
NF449, a sulfated compound derived from the antiparasitic drug suramin, was previously reported to inhibit infection by enterovirus A71 (EV-A71). In the current work, we found that NF449 inhibits virus attachment to target cells, and specifically blocks virus interaction with two identified receptors--the P-selectin ligand, PSGL-1, and heparan sulfate glycosaminoglycan--with no effect on virus binding to a third receptor, the scavenger receptor SCARB2. We also examined a number of commercially available suramin analogues, and newly synthesized derivatives of NF449; among these, NF110 and NM16, like NF449, inhibited virus attachment at submicromolar concentrations. PSGL-1 and heparan sulfate, but not SCARB2, are both sulfated molecules, and their interaction with EV-A71 is thought to involve positively charged capsid residues, including a conserved lysine at VP1-244, near the icosahedral 5-fold vertex. We found that mutation of VP1-244 resulted in resistance to NF449, suggesting that this residue is involved in NF449 interaction with the virus capsid. Consistent with this idea, NF449 and NF110 prevented virus interaction with monoclonal antibody MA28-7, which specifically recognizes an epitope overlapping VP1-244 at the 5-fold vertex. Based on these observations we propose that NF449 and related compounds compete with sulfated receptor molecules for a binding site at the 5-fold vertex of the EV-A71 capsid.


Total intravenous anesthesia with etomidate. I. A trial in children.
Eighty children, aged from 2 weeks to 14 years, were anesthetized using intravenous agents only. Anesthesia was induced by etomidate 0.3 mg/kg together with atropine and fentanyl 2 to 5 microgram/kg. Muscle relaxation was provided by suxamethonium, alcuronium or pancuronium. Unconsciousness was maintained using a continuous infusion of etomidate, initially 0.04-0.05 mg/kg/minute, but adjusted to the apparent requirements of the child. Oxygen, or oxygen/air mixtures were inhaled, or used for ventilation. Maintenance of anesthesia was assessed as good in only 85% of patients, with movement in response to surgery being seen in the remaining 15%. Unsatisfactory anesthesia was particularly associated with lack of experience in the technique, and unparalysed patients. Recovery was generally good, and rapid, with a mean waking time of 4.8 minutes. It is unlikely that this technique will find widespread use. It demands constant observation of the patient, looking for signs of consciousness; and trying to avoid having an awake, paralysed patient, or giving an overdose of etomidate.


North Indian state of Uttarakhand: a new hothouse of visceral leishmaniasis.
Visceral leishmaniasis (VL) has been reported in the last decade from the hilly state of Uttarakhand, India. We report 47 cases from the non-endemic Garhwal region of this state which, over the last 10 years, were treated successfully. We conclude that the transmission cycle of VL is established in this region. Effective vector control measures are warranted to prevent the disease becoming a health problem, albeit not a major one given its excellent response to drugs.


Congenital toxoplasmosis and reinfection during pregnancy: case report, strain characterization, experimental model of reinfection, and review.
We present a case of disseminated congenital toxoplasmosis in a newborn born to a mother who had been immunized against toxoplasmosis before conception. The mother was reinfected, likely by ingestion of imported raw horse meat during pregnancy. This clinical presentation is exceptional in France and raised the possibility of infection by a highly virulent Toxoplasma strain. The strain responsible was isolated from the peripheral blood of the newborn, and when genotyped with microsatellite markers, it exhibited an atypical genotype, one which is very uncommon in Europe but had been described in South America. We tested the hypothesis of a reinfection with a different genotype by using an experimental mouse model, which confirmed that acquired immunity against European Toxoplasma strains may not protect against reinfection by atypical strains acquired during travel outside Europe or by eating imported meat.


Keloidal basal cell carcinoma after radiation therapy.
We report a case of keloidal basal cell carcinoma (BCC) that developed after radiation therapy. A 67-year-old Japanese man had received radiation therapy of an unknown amount for three years for the treatment of right cervical lymph node tuberculosis at the age of 7. Within the area of chronic radiation dermatitis, on the right preauricular region, he presented with a skin-colored to erythematous, firm nodule. Histopathologically, this nodule showed features of keloidal BCC. The stroma characteristically demonstrated the prominent, keloidal, thickened collagen bundles standing out against the surrounding actinic-damaged dermis, and well-circumscribed, keloidal collagen bundles that proliferated in a nodular form almost corresponding to a clinically firm, nodular lesion. There was no radiation fibrosis around the keloidal BCC. We discuss the differences between keloidal BCC and morpheiform BCC, and consider keloidal BCC to be a rare variant of BCC from a clinico- pathological basis.


Pharmacists' role in harm reduction: a survey assessment of Kentucky community pharmacists' willingness to participate in syringe/needle exchange.
Pharmacists' role in harm reduction is expanding in many states, yet there are limited data on pharmacists' willingness to participate in harm reduction activities. This study assessed community pharmacists' willingness to participate in one harm reduction initiative: syringe/needle exchange. In 2015, all Kentucky pharmacists with active licenses were emailed a survey that examined attitudes towards participation in syringe/needle exchange. Response frequencies were calculated for community pharmacist respondents. Ordinal logistic regression estimated the impact of community pharmacist characteristics and attitudes on willingness to provide clean needles/syringes to people who inject drugs and to dispose of used syringes/needles, where both dependent variables were defined as Likert-type questions on a scale of 1 (not at all willing) to 6 (very willing). Of 4699 practicing Kentucky pharmacists, 1282 pharmacists responded (response rate = 27.3%); the majority (n = 827) were community pharmacists. Community pharmacists were divided on willingness to provide clean needles/syringes, with 39.1% not willing (score 1 or 2 of 6) and 30% very willing (score 5 or 6 of 6). Few were willing to dispose of used needles/syringes, with only 18.7% willing. Community pharmacists who agreed that pharmacists could have significant public health impact by providing access to clean needles expressed 3.56 times more willingness to provide clean needles (95% CI 3.06-4.15), and 2.04 times more willingness to dispose of used needles (95% CI 1.77-2.35). Chain/supermarket pharmacists (n = 485, 58.6% of community pharmacies) were 39% less likely to express willingness to dispose of used needles (95% CI 0.43-0.87) when compared with independent community pharmacists (n = 342, 41.4% of community pharmacies). Independent pharmacists reported different barriers (workflow) than their chain/supermarket pharmacist colleagues (concerns of clientele). Kentucky community pharmacists were more willing to provide clean needles than to dispose of used needles. Strategies to mitigate barriers to participation in syringe/needle exchange are warranted.


A Capabilities Approach to Environmental Impact on Nursing Home Resident Quality of Life.
Nursing homes are the major provider of intermediate and long-term care outside of the hospital setting to individuals whose capacity for self-care is limited due to physical or cognitive impairments. Yet, despite their need for assistance, residents of nursing homes want to control their lives, set their routines, and do enjoyable things. The extent to which residents can maintain autonomy and dignity is important. The current study suggests an environmental gerontological framework, rooted in a capabilities approach, that can be used to consider environmental impact on quality of life in nursing homes. Using a cross-sectional survey of nursing home residents in Texas, environmental factors that might predict residents' quality of life as well as possible interactions of environmental factors and residents' characteristics that might predict well-being were examined. Environmental orientation and perception of social activities were important predictors of residents' quality of life, but geographic location and facility size were not important predictors. [Res Gerontol Nurs. 2017; 10(4):162-170.].


Prediction of MLH1 and MSH2 mutations in Lynch syndrome.
Lynch syndrome is caused primarily by mutations in the mismatch repair genes MLH1 and MSH2. To analyze MLH1/MSH2 mutation prevalence in a large cohort of patients undergoing genetic testing and to develop a clinical model to predict the likelihood of finding a mutation in at-risk patients. Personal and family history were obtained for 1914 unrelated probands who submitted blood samples starting in the year 2000 for full gene sequencing of MLH1/MSH2. Genetic analysis was performed using a combination of sequence analysis and Southern blotting. A multivariable model was developed using logistic regression in an initial cohort of 898 individuals and subsequently prospectively validated in 1016 patients. The complex model that we have named PREMM(1,2) (Prediction of Mutations in MLH1 and MSH2) was developed into a Web-based tool that incorporates personal and family history of cancer and adenomas. Deleterious mutations in MLH1/MSH2 genes. Overall, 14.5% of the probands (130/898) carried a pathogenic mutation (MLH1, 6.5%; MSH2, 8.0%) in the development cohort and 15.3% (155/1016) in the validation cohort, with 42 (27%) of the latter being large rearrangements. Strong predictors of mutations included proband characteristics (presence of colorectal cancer, especially > or =2 separate diagnoses, or endometrial cancer) and family history (especially the number of first-degree relatives with colorectal or endometrial cancer). Age at diagnosis was particularly important for colorectal cancer. The multivariable model discriminated well at external validation, with an area under the receiver operating characteristic curve of 0.80 (95% confidence interval, 0.76-0.84). Personal and family history characteristics can accurately predict the outcome of genetic testing in a large population at risk of Lynch syndrome. The PREMM(1,2) model provides clinicians with an objective, easy-to-use tool to estimate the likelihood of finding mutations in the MLH1/MSH2 genes and may guide the strategy for molecular evaluation.


Xylochemistry--Making Natural Products Entirely from Wood.
The first total synthesis of the dimeric berberine alkaloid ilicifoline (ilicifoline B) is reported. Its carbon skeleton is constructed from ferulic acid, veratrole, and methanol. The synthesis reported herein employs starting materials solely derived from wood. The natural product is thus constructed entirely from renewable resources. The same strategy is applied to a formal total synthesis of morphinan alkaloids. The use of wood-derived building blocks (xylochemicals) instead of the conventional petrochemicals represents a sustainable alternative to classical synthetic approaches.


[Total and lipid-bound sialic acids in the blood in primary and secondary hyperlipoproteinemias].
Total and lipid-bound sialic acids (TSA and LBSA) were measured in the blood of 219 patients with primary or secondary hyperlipoproteinemia (129 patients with ischemic heart disease and 66 patients with diabetes mellitus type II) versus 24 normolipidemic healthy subjects. TSA levels in IHD patients differed significantly from those in IHD-free and diabetic patients. LBSA quantities were the same in IHD and IHD-free patients, being significantly higher in diabetes mellitus than in IHD. These findings give no proves to diagnostic value of TSA and LBSA as markers of IHD and coronary atherosclerosis. TSA levels may be used in the test for disturbed lipoprotein metabolism.


A Comparison of Postoperative Outcomes Between Immediate, Delayed Immediate, and Delayed Autologous Free Flap Breast Reconstruction: Analysis of 2010-2020 NSQIP Data.
While many factors influence decisions related to the timing between mastectomy and flap-based breast reconstruction, there is limited literature comparing postoperative complications between immediate (IBR), delayed immediate (DIBR), and delayed (DBR) reconstruction modalities. Using the National Surgical Quality Improvement Program (NSQIP), we sought to compare postoperative complication rates of each timing modality. The NSQIP 2010-2020 database was queried for patients who underwent free flap breast reconstruction. Cases were categorized to include mastectomy performed concurrently with a free flap reconstruction, removal of a tissue expander with free flap reconstruction, and free flap reconstruction alone which are defined as IBR, DIBR, and DBR, respectively. The frequency of postoperative outcomes including surgical site infection (SSI), wound dehiscence, intraoperative transfusion, deep venous thrombosis (DVT), and return to operating room (OR) was assessed. Overall complication rates, hospital length of stay (LOS), and operative time were analyzed. Multivariable regression analysis controlling for age, race, BMI, diabetes, hypertension, ASA class, and laterality was performed. A total of 7,907 cases that underwent IBR, DIBR (n = 976), and DBR reconstruction (n = 6,713) were identified. No statistical difference in occurrence of SSIs, wound dehiscence, or DVT was identified. DIBR (9%) and DBR (11.9%) were associated with less occurrences of reoperation than IBR (13.2%, p < 0.001). Univariate and multivariate regression analysis demonstrated that DIBR and DBR were associated with a lower odds of complications and shorter operation time versus IBR. No statistically significant differences between DIBR and DBR in surgical complications, LOS, and operative time were identified. Awareness of overall complication rates associated with each reconstructive timing modality can be used to help guide physicians when discussing reconstructive options. Our data suggests that DIBR and DBR are associated with less overall complications than IBR. Physicians should continue to consider patients' unique circumstances when deciding upon which timing modality is appropriate.


Separation and recovery of radioactive and non-radioactive toxic trace elements from aqueous industrial effluents.
An update is presented on liquid membrane-based processes as viable and relevant alternatives to conventional approaches such as precipitation, solvent extraction, ion exchange processes and electrochemical techniques for the removal and recovery of some toxic and/or valuable trace metal ions including some actinides and fission products e.g. U, Am, Y etc and As, Cd, Co, Cr, Cu, Hg, Ni, Pb, Zn etc from radioactive as well as non-radioactive aqueous waste solutions respectively. In particular, results of experiments aimed at developing supported liquid membrane(SLM)-based process using commercially available porous membranes and indigenously prepared track--etch membranes (TEMs) have been critically examined in laboratory studies to generate basic data needed to evaluate their utility for continuous operation without regeneration. These include effect of pore size, porosity, optimum pore size and their reusability. It is clearly demonstrated that indigenously prepared 10 microm thick TEMs with a porosity in the range of 2-5% give comparable transport rates for metal ions-matching with that of commercial membranes of much higher thickness (160 microm) and higher porosity of 60-85%. The smaller thickness of TEMs more than compensates for their lower porosity. It is shown that because of their well defined pore characteristics TEMs could serve as model supports in SLM studies. By comparing the values of permeability coefficient (P) for TEM and polytetraflouroethylene (PTFE) supports for the transport of Pb2+ chosen as a typical divalent metal ion, and using di-2 ethyl hexyl phosphoric acid (D2EHPA) as the carrier, it is unambiguously proved that diffusion of the metal complex across the membrane is the rate controlling step in metal ion transport in SLM-based processes. An overview of the experimental findings along with future outlook and suggestions for further work are presented in this paper.


[Intracranial hypertension and ependymoma of the end of the spinal cord].
A 42 year-old woman was admitted with a subacute intracranial hypertension which improved under medical treatment. Angiographic data and CT scan showed enlarged ventricles. CSF showed 1.95 g/l of proteins. Five months later, a relapsing acute intracranial hypertension led to a ventricular derivation. CT scans, angiographies and ventriculography showed progressively enlarged ventricles but failed to disclose any intracranial tumor. A thoraco-lumbar tumor of the spinal cord was incidentally discovered and removed. Histopathology concluded to an ependymoma. No sign of recurrence has occurred after an eighteen month follow up. The pathogenesis of intracranial hypertension occurring in spinal cord tumors is discussed.


Early-Life Exposure to Lead Induces Cognitive Impairment in Elder Mice Targeting SIRT1 Phosphorylation and Oxidative Alterations.
Pb is a potential risk factor for cognition, mainly mediated by enhanced oxidative stress. Resveratrol, a natural polyphenol with crucial anti-oxidative property, is recently implicated in preventing cognitive deficits in normal aging and neurodegenerative disorders. Its beneficial effects have been linked to sirtuin 1(SIRT1) activation. The aim of this work is to investigate the possible linkage between alterations in Pb-induced oxidative damage and cognitive impairment by prolonged treatment of resveratrol. Male C57BL/6 mice were given Pb(Ac)2 treatment or deionized H2O for 12 weeks, and subjected to resveratrol gavage at the dose of 50 mg/kgBw•d or vehicle after Pb exposure. Results from biochemical analysis and immunohistofluorescence showed that Pb induced oxidative DNA damage and decreased cortical antioxidant biomarker. As expected, these abnormalities were improved by resveratrol treatment. Morris water maze test, Western blotting, immunohistofluorescence staining and RT-qPCR indicated that resveratrol ameliorated spatial learning and memory deficits with alterations in hippocampal BDNF-TrkB signaling, promoted nuclear localization and phosphorylation of hippocampal SIRT1, partly increased protein levels of AMPK and PGC-1α involving in modulation of antioxidant response in Pb-exposed mice. Our results support the hypothesis that resveratrol could attenuate Pb-induced cognitive impairment which was associated with activating SIRT1 via modulation of oxidative stress. Additionally, resveratrol also repressed the Pb-induce amyloidogenic processing with resultant decline in cortical Aβ1--40. Noteworthy, such effects were not mediated by resveratrol treatment alone. These findings emphasize the potential of SIRT1 activator as an efficacious dietary intervention to downgrade the Pb-induced neurotoxic lesion.


Therapeutic efficacy of itraconazole in systemic candidosis in guinea pigs.
Fifty non-immunocompromised guinea pigs were infected by the intravenous route with 8,000 blastospores of Candida albicans per gram body weight: 26 were treated orally with the excipient, 12 with itraconazole at 1.25 mg X kg-1 and 12 at 5 mg X kg-1, once daily for 14 days starting on the day of infection. Hematology was checked for all animals before infection and on days 7, 14 and 17 after infection. Histopathological examinations were done for 2 animals of each group on days 7, 14 and 17. The infection and the therapeutic efficacy were checked by clinical observation, at autopsy and by cultures of organs. Itraconazole was highly active at both concentrations, resulting in clinical cure, negativation of cultures, normalisation of the blood picture and absence of fungal elements and presence of only small remnants of lesions on days 14 and 17 in some organs. No drug-related side effects were observed.


The frailty index outperforms DNA methylation age and its derivatives as an indicator of biological age.
The measurement of biological age as opposed to chronological age is important to allow the study of factors that are responsible for the heterogeneity in the decline in health and function ability among individuals during aging. Various measures of biological aging have been proposed. Frailty indices based on health deficits in diverse body systems have been well studied, and we have documented the use of a frailty index (FI34) composed of 34 health items, for measuring biological age. A different approach is based on leukocyte DNA methylation. It has been termed DNA methylation age, and derivatives of this metric called age acceleration difference and age acceleration residual have also been employed. Any useful measure of biological age must predict survival better than chronological age does. Meta-analyses indicate that age acceleration difference and age acceleration residual are significant predictors of mortality, qualifying them as indicators of biological age. In this article, we compared the measures based on DNA methylation with FI34. Using a well-studied cohort, we assessed the efficiency of these measures side by side in predicting mortality. In the presence of chronological age as a covariate, FI34 was a significant predictor of mortality, whereas none of the DNA methylation age-based metrics were. The outperformance of FI34 over DNA methylation age measures was apparent when FI34 and each of the DNA methylation age measures were used together as explanatory variables, along with chronological age: FI34 remained significant but the DNA methylation measures did not. These results indicate that FI34 is a robust predictor of biological age, while these DNA methylation measures are largely a statistical reflection of the passage of chronological time.


Success or Failure? Are We Meeting the Needs of Children With Developmental Coordination Disorder?
Background. Current international clinical practice guidelines indicate that children with developmental coordination disorder (DCD) should receive therapy, yet school and community-based occupational therapy is not standard of care. Purpose. To understand parent perspectives on best practice for treatment and what supports and services are required to meet their children's needs. Method. An online cross-sectional survey (impACT for DCD) was distributed to parents of children <18 years with self-reported suspected or diagnosed DCD living in British Columbia. Data analysis included descriptive statistics and contingency analyses to explore whether access to therapy differed with income, age of child, or geographical location. Open-ended questions were analyzed using content analysis. Findings. Of the 237 respondents, 194 children had suspected/confirmed DCD; however, only 20% (38/198) of the children had received therapy at school. Some parents (32/58) pursued private therapy. Geographic location and income had no relationship with therapy access (p > 0.05). Parents expressed frustration with poor awareness and understanding of the impact of DCD among educators, health-care professionals, and community members, and identified the need for funded and accessible school and community services and supports. Conclusion. Evidenced-based occupational therapy intervention should be standard of care for children with DCD as per clinical guidelines and parent-identified need.


Renal and Inflammatory Proteins as Biomarkers of Diabetic Kidney Disease and Lupus Nephritis.
Current methods for differentiation of kidney disease types are unspecific and may be invasive. Thus, there is a need for development of new biomarkers of kidney disorders that are specific and less invasive. In this study, we analyzed serum samples of diabetic kidney disease (DKD) and lupus nephritis (LN) patients to identify biomarkers of these two disorders. Serum samples were analyzed by Simple Plex assays. We calculated the area under the curve (AUC) as well as receiver operating characteristics (ROC) to obtain the sensitivity and specificity and other biomarker-related variables of apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), interleukin- (IL-) 18, Lipocalin-2/NGAL, epidermal growth factor (EGF), u-Plasminogen Activator (uPA), and C-reactive protein (CRP) as potential biomarkers. Protein levels of ASC, IL-18, EGF, and Lipocalin-2/NGAL were higher in DKD and LN patients when compared to controls, whereas only uPA was elevated in DKD patients and CRP in LN patients. As determined by the AUC, of the six analytes studied, EGF (AUC = 0.9935), Lipocalin-2/NGAL (0.9554), ASC (0.7666), and uPA (0.7522) are reliable biomarkers of DKD, whereas EGF (1.000), Lipocalin-2/NGAL (0.9412), uPA (0.7443), and IL-18 (0.7384) are more reliable for LN. The biomarkers analyzed can differentiate between healthy and affected individuals. However, there was no difference between the levels of these biomarkers in DKD vs LN. Thus, although these biomarkers cannot be used to categorize patients between DKD and LN, they are useful as biomarkers of renal pathology.


Discovery of BI 7446: A Potent Cyclic Dinucleotide STING Agonist with Broad-Spectrum Variant Activity for the Treatment of Cancer.
Activating the stimulator of interferon genes (STING) pathway with STING agonists is an attractive immune oncology concept to treat patients with tumors that are refractory to single-agent anti-PD-1 therapy. For best clinical translatability and broad application to cancer patients, STING agonists with potent cellular activation of all STING variants are desired. Novel cyclic dinucleotide (CDN)-based selective STING agonists were designed and synthesized comprising noncanonical nucleobase, ribose, and phosphorothioate moieties. This strategy led to the discovery of 2',3'-CDN 13 (BI 7446), which features unprecedented potency and activates all five STING variants in cellular assays. ADME profiling revealed that CDN 13 has attractive drug-like properties for development as an intratumoral agent. Injection of low doses of CDN 13 into tumors in mice induced long-lasting, tumor-specific immune-mediated tumor rejection. Based on its compelling preclinical profile, BI 7446 has been advanced to clinical trials (monotherapy and in combination with anti-PD-1 antibody).


Overwork and cerebrocardiovascular disease in Korean adult workers.
Long work hours and overwork may increase the cardiovascular load of workers. But long work hours and overwork are not the same. Cardiovascular overload from working is dependent on the physical demand of the work and the worker's physical fitness, as well as the working hours. This cross-sectional study was designed to identify the association between overwork and cerebrocardiovascular disease, taking into account the physical demand of work, physical fitness, and work hours. Study data were obtained from surveillance of occupational cerebrocardiovascular disease. Questionnaire surveys including general and work-related characteristics were conducted. Maximum acceptable work time was estimated using the physical work demand and physical fitness of the subjects. The overwork index, which was the ratio of maximum acceptable work time and actual work hours of the subjects, was calculated. In the workers with a moderate or high physical demand of work, the adjusted odds ratios for overwork indexes of 1.01-1.20, 1.21-1.50, and >1.50 were 2.679 (95% confidence interval (CI) 1.025-6.999), 3.124 (95% CI 1.111-8.783), and 4.331 (95% CI 1.719-10.908), respectively. The results indicate that the risk of cerebrocardiovascular disease might be high in the workers with long working hours, high physical demand of work, and poor physical fitness engaged in work with a moderate to high physical work demand. Work hours should be accommodated according to the worker's physical fitness and the physical demand of work, and this could lower the risk of cerebrocardiovascular disease.


Use of porcine dermis as a dural substitute in 72 patients.
Experience over a 2-year period with the use of porcine dermis as a dural substitute is reported. In this series, porcine dermis was used for dural repair in a total of 72 patients. In a further 28 patients, one of the authors (A.E.B.) used porcine dermis to wrap lumbar nerve roots at the time of surgery for either prolapsed intervertebral disc or extradural lumbar nerve root adhesions. The authors report the advantages of this material which include ready availability and low cost. It is extremely pliable, easy to handle, and can be applied to relatively inaccessible areas. It appears to become rapidly adherent so that suture fixation is frequently not required. No evidence of a foreign-body inflammatory response has been found. No untoward result has been encountered in the 28 patients in whom porcine dermis was used to wrap lumbar nerve roots but it remains too early to show whether this will reduce the incidence of postoperative extradural adhesions.


Perceiving a calling, living a calling, and calling outcomes: How mentoring matters.
In this study, we integrate two careers-related literatures-callings research and mentoring research-by examining how mentoring relationships might help close the gap between people's perception of a calling and actually living out their calling. Drawing on work as calling theory (WCT; Duffy, Dik, Douglass, England, & Velez, 2018) as a framework, our results first revealed that, consistent with previous research, perceiving a calling is an important antecedent to living a calling. However, in our sample of 129 U.S. teachers, results further showed that the relationship between perceiving a calling and living a calling is stronger for those with a mentor in their profession. We additionally extend WCT by examining both positive and potentially negative outcomes associated with living a calling, focusing on stress-related outcomes. Our findings revealed that, in addition to reporting higher levels of job satisfaction and work engagement, those who were living their calling experienced lower rates of stress-related absenteeism and reported fewer somatic complaints than those who did not believe they were living their calling. In sum, this study is unique in its integration of two focal careers-related literatures, and it provides practical implications for professionals, counselors, educators, and organizations. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Multiple-barrier disinfection by chlorination and UV irradiation for desalinated drinking waters: chlorine photolysis and accelerated lamp-sleeve fouling effects.
Experiments were conducted to quantify interaction effects between UV irradiation and chlorination for desalinated drinking water. The rate of chlorine photolysis in desalinated water was characterized using a low-pressure UV lamp and chlorine doses typical of drinking water treatment and was found to be lower than reported photolysis rates for treated surface water. Results indicate that, for most desalinated water applications, reduction in free chlorine is likely to be limited, but, depending on the UV dose used, not necessarily negligible. Investigation of the potential for reactor lamp-sleeve fouling included mineral speciation and solubility modeling and showed that chlorination of desalinated water before UV disinfection may increase lamp-sleeve fouling, particularly for point-of-use reactors. UV irradiation before chlorination may minimize fouling. Overall results point to the variable nature of UV lamp-sleeve fouling and chlorine photolysis and an intrinsic dependence on local water chemistry conditions.


Cortical reorganization in postlingually deaf cochlear implant users: Intra-modal and cross-modal considerations.
With the advances of cochlear implant (CI) technology, many deaf individuals can partially regain their hearing ability. However, there is a large variation in the level of recovery. Cortical changes induced by hearing deprivation and restoration with CIs have been thought to contribute to this variation. The current review aims to identify these cortical changes in postlingually deaf CI users and discusses their maladaptive or adaptive relationship to the CI outcome. Overall, intra-modal and cross-modal reorganization patterns have been identified in postlingually deaf CI users in visual and in auditory cortex. Even though cross-modal activation in auditory cortex is considered as maladaptive for speech recovery in CI users, a similar activation relates positively to lip reading skills. Furthermore, cross-modal activation of the visual cortex seems to be adaptive for speech recognition. Currently available evidence points to an involvement of further brain areas and suggests that a focus on the reversal of visual take-over of the auditory cortex may be too limited. Future investigations should consider expanded cortical as well as multi-sensory processing and capture different hierarchical processing steps. Furthermore, prospective longitudinal designs are needed to track the dynamics of cortical plasticity that takes place before and after implantation.


Primary composite lymphoma of the lung: a case report.
Herein, we report a rare case of primary lung lymphoma in a 61 year-old woman with a history of 6-month nonspecific symptoms like dry cough, fever, chills and weight loss. She was admitted to a hospital and received broad-spectrum antibiotics but discharged without full recovery. In her second hospital admission, a bronchoscopic evaluation and transbronchial biopsy were performed, which were not diagnostic. Finally, an open lung biopsy was done. Immunohistochemical (IHC) staining of the specimen suggested pulmonary Hodgkin lymphoma. Because of disease recurrence, a second bronchoscopy was performed and endobronchial biopsy revealed transformation to anaplastic lymphoma. In the second recurrence, we decided to reevaluate the last biopsy specimens in greater details. Finally, after conduction of several staining patterns, the diagnosis of primary composite lymphoma of the lung was made.


Outcomes research analysis of continuous intratympanic glucocorticoid delivery in patients with acute severe to profound hearing loss: basis for planning randomized controlled trials.
The data presented herein form the basis for conducting randomized placebo-controlled clinical trials evaluating the safety and efficacy of salvage treatment in patients with idiopathic sudden severe sensorineural hearing loss (but not anacusis) refractory to initial systemic therapy. Comparison of different application protocols and drug delivery systems will allow assessment of the value of continuous versus intermittent intratympanic glucocorticoid drug delivery. To describe and critically evaluate the results of continuous intratympanic glucocorticoid delivery in patients with acute unilateral severe and profound sensorineural hearing loss refractory to initial systemic therapy and to compare the outcome with a historical control group. In a retrospective chart review, treatment results were analyzed in 23 patients with acute severe and profound hearing loss and failure of systemic standard therapy who received a continuous intratympanic delivery of glucocorticoids as a salvage treatment. Audiological results were compared within the local therapy group and with the results of an historical control group who did not receive salvage treatment. The study and control groups were matched with respect to hearing loss after initial systemic treatment failure. The average pure-tone threshold after intratympanic salvage treatment showed a statistically significant improvement of 15 dB (95% CI 7-24 dB; p<0.001). After exclusion of patients with complete anacusis, i.e. a non-measurable hearing threshold, the local therapy group showed a significantly better improvement (mean 19 dB; 95% CI 6-32 dB) than the historical control group (mean 5 dB; 95% CI -2-11 dB; p<0.05).


Characterization of the repertoire of hypervariable regions in the Protein II (opa) gene family of Neisseria gonorrhoeae.
P.II outer membrane proteins of Neisseria gonorrhoeae are encoded by a family of closely related genes. Although the genes are highly conserved, major differences in sequence among them occur in two short regions, designated hypervariable regions 1 (HV1) and 2 (HV2). In this study, we determined the number and DNA sequence of the hypervariable regions in the P.II genes of strains FA1090. The FA1090 chromosome contained at least eleven P.II loci, having six different versions each of HV1 and HV2 among them. Southern blotting with HV-specific oligonucleotides showed that each version was present in one to three copies, and that there were nine unique combinations of HV1 and HV2 in the P.II genes. Although each of the versions of HV1 or HV2 had a unique DNA sequence, there were some similarities among them, particularly when certain ones were compared. Restriction fragments containing only the HV regions were cloned into an expression vector to demonstrate that the epitopes recognized by a set of monoclonal antibodies specific for different FA1090 P.II proteins were completely encoded by either HV1 or HV2.


What do they do? Interactions between village doctors and medical representatives in Chakaria, Bangladesh.
Informally trained village doctors supply the majority of healthcare services to the rural poor in many developing countries. This study describes the demographic and socio-economic differences between medical representatives (MRs) and village doctors in rural Bangladesh, and explores the nature of their interactions. This study was conducted in Chakaria, a rural sub-district of Bangladesh. Focus group discussions and in-depth interviews were conducted, along with a quantitative survey to understand practice perceptions. Data analysis was performed using grounded theory and bivariate statistical tests. We surveyed 43 MRs and 83 village doctors through 22 focus group discussions and 33 in-depth interviews. MRs have a higher average per capita monthly expenditure compared to village doctors. MRs are better educated with 98% having bachelor's degrees whereas 84% of village doctors have twelfth grade education or less (p<0.001). MRs are the principal information source about new medications for the village doctors. Furthermore, incentives offered by MRs and credit availability influence the prescription practices of village doctors. MRs being the key player in providing information about drugs to village doctors might influence their prescription practices. Improvements in the quality of healthcare delivered to the rural poor in informal provider-based health markets require stricter regulations and educational initiatives for providers and MRs.


Extracellular Succinate: A Physiological Messenger and a Pathological Trigger.
When tissues are under physiological stresses, such as vigorous exercise and cold exposure, skeletal muscle cells secrete succinate into the extracellular space for adaptation and survival. By contrast, environmental toxins and injurious agents induce cellular secretion of succinate to damage tissues, trigger inflammation, and induce tissue fibrosis. Extracellular succinate induces cellular changes and tissue adaptation or damage by ligating cell surface succinate receptor-1 (SUCNR-1) and activating downstream signaling pathways and transcriptional programs. Since SUCNR-1 mediates not only pathological processes but also physiological functions, targeting it for drug development is hampered by incomplete knowledge about the characteristics of its physiological vs. pathological actions. This review summarizes the current status of extracellular succinate in health and disease and discusses the underlying mechanisms and therapeutic implications.


Lead-Free Piezoceramics: Revealing the Role of the Rhombohedral-Tetragonal Phase Coexistence in Enhancement of the Piezoelectric Properties.
Until now, lead zirconate titanate (PZT) based ceramics are the most widely used in piezoelectric devices. However, the use of lead is being avoided due to its toxicity and environmental risks. Indeed, the attention in piezoelectric devices has been moved to lead-free ceramics, especially on (K,Na)NbO3-based materials, due to growing environmental concerns. Here we report a systematic evaluation of the effects of the compositional modifications induced by replacement of the B-sites with Sb(5+) ions in 0.96[(K0.48Na0.52)0.95Li0.05Nb1-xSbxO3]-0.04[BaZrO3] lead-free piezoceramics. We show that this compositional design is the driving force for the development of the high piezoelectric properties. So, we find that this phenomenon can be explained by the stabilization of a Rhombohedral-Tetragonal (R-T) phase boundary close to room temperature, that facilities the polarization process of the system and exhibits a significantly high piezoelectric response with a d33 value as high as ∼400 pC/N, which is comparable to part soft PZTs. As a result, we believe that the general strategy and design principles described in this study open the possibility of obtaining (K,Na)NbO3-based lead-free ceramics with enhanced properties, expanding their application range.


[Epiphyseal growth after replantation in childhood].
Long-term results in 17 patients with 19 replanted parts of the upper extremity after replantation during childhood are presented. Regarding longitudinal epiphyseal growth, three patients had normal growth. In 15 cases, average length of the replanted digits attained 88.6% of normal and one patient gained overgrowth of 118% of normal. In every case, consolidation of the fracture was seen. Four patients developed a deviation of the replanted finger in the frontal plane. The cause of deviation in every case was incorrect primary reposition and not a disturbance of growth of the replanted epiphysis.


Error detection and representation in the olivo-cerebellar system.
Complex spikes generated in a cerebellar Purkinje cell via a climbing fiber have been assumed to encode errors in the performance of neuronal circuits involving Purkinje cells. To reexamine this notion in this review, I analyzed structures of motor control systems involving the cerebellum. A dichotomy was found between the two types of error: sensory and motor errors play roles in the feedforward and feedback control conditions, respectively. To substantiate this dichotomy, here in this article I reviewed recent data on neuronal connections and signal contents of climbing fibers in the vestibuloocular reflex (VOR), optokinetic eye movement response, saccade, hand reaching, cursor tracking, as well as some other cases of motor control. In our studies, various sources of sensory and motor errors were located in the neuronal pathways leading to the inferior olive. We noted that during the course of evolution, control system structures involving the cerebellum changed rather radically from the prototype seen in the flocculonodular lobe and vermis to that applicable to the cerebellar hemisphere. Nevertheless, the dichotomy between sensory and motor errors is maintained.


Whole Genome Sequencing Expands Diagnostic Utility and Improves Clinical Management in Pediatric Medicine.
The standard of care for first-tier clinical investigation of the etiology of congenital malformations and neurodevelopmental disorders is chromosome microarray analysis (CMA) for copy number variations (CNVs), often followed by gene(s)-specific sequencing searching for smaller insertion-deletions (indels) and single nucleotide variant (SNV) mutations. Whole genome sequencing (WGS) has the potential to capture all classes of genetic variation in one experiment; however, the diagnostic yield for mutation detection of WGS compared to CMA, and other tests, needs to be established. In a prospective study we utilized WGS and comprehensive medical annotation to assess 100 patients referred to a paediatric genetics service and compared the diagnostic yield versus standard genetic testing. WGS identified genetic variants meeting clinical diagnostic criteria in 34% of cases, representing a 4-fold increase in diagnostic rate over CMA (8%) (p-value = 1.42e-05) alone and >2-fold increase in CMA plus targeted gene sequencing (13%) (p-value = 0.0009). WGS identified all rare clinically significant CNVs that were detected by CMA. In 26 patients, WGS revealed indel and missense mutations presenting in a dominant (63%) or a recessive (37%) manner. We found four subjects with mutations in at least two genes associated with distinct genetic disorders, including two cases harboring a pathogenic CNV and SNV. When considering medically actionable secondary findings in addition to primary WGS findings, 38% of patients would benefit from genetic counseling. Clinical implementation of WGS as a primary test will provide a higher diagnostic yield than conventional genetic testing and potentially reduce the time required to reach a genetic diagnosis.


A novel p.E121G heterozygous missense mutation of SOD1 in an apparently sporadic ALS case with a 14-year course.
The frequency of SOD1 mutations differs among populations: in Italy they account for 13.6% of familial ALS and 0.7% of sporadic cases. We describe an apparently sporadic Italian ALS patient, carrying a novel p.E121G heterozygous missense mutation of SOD1, with a 14-year disease course and a prevalent lower motor neuron phenotype, which are not uncommon among SOD1 mutations carriers. To our knowledge, no other mutation of codon 121 of SOD1 has ever been reported. Three in silico models suggest a deleterious effect of the p.E121G mutation. Nevertheless, further studies are necessary to confirm its pathogenic role and to evaluate eventual genotype-phenotype correlations.


HISTORICAL BIOGEOGRAPHY IN NORTH AMERICAN ARID REGIONS: AN APPROACH USING MITOCHONDRIAL-DNA PHYLOGENY IN GRASSHOPPER MICE (GENUS ONYCHOMYS).
Restriction-endonuclease-site variation of mitochondrial DNA (mtDNA) was used to investigate patterns of geographic and phylogenetic divergence within the rodent genus Onychomys. Onychomys has occupied arid habitats in the western North American deserts, shrub-steppes, and grasslands since the late Tertiary. A phylogenetic analysis of the total mtDNA restriction-site variation throughout the range of Onychomys suggests that the distribution of this genus has been affected by the same Quaternary pluvial-interpluvial climatic fluctuations that have resulted in the periodic fragmentation of arid habitats in western North America. Onychomys mtDNA haplotypes define at least five discrete geographical subsets, suggesting that there are five areas of endemism for biota restricted to arid and semiarid habitats in North America. The mtDNA-haplotype phylogeny can be used to infer an hypothesis of historical relationships among the five areas of endemism as follows: ([{(Wyoming Basin + Interior Plains + Colorado Plateaus) + (Columbia Basin + Great Basin)} + Gulf Coastal Plain] + Chihuahuan) + Western Deserts. The results of this study point to the potential use of mtDNA-haplotype phylogenies to reconstruct historical biogeographic events in Quaternary time. The utility of mtDNA variation depends in part on the ecology and distribution of the species being examined. Therefore, our hypothesized area cladogram can be tested by investigating regional relationships in other western North American taxa with distributions similar to Onychomys.


Preliminary study for a newly designed silicone stent and delivery system for canine obstructive tracheal disease.
The goal of this study was to prove the possibility of using silicone stents broadly used for human medicine in canine obstructive tracheal disease. A silicone stent anatomically designed for canine trachea was tested on 5 beagle dogs for 8 weeks. The stent was carefully inserted using a newly developed delivery device under fluoroscopic guidance. There were no technical difficulties in placing the stent during the procedure. Previously reported complications of airway stenting such as stent migration or granulation tissue formation did not occur in any of the cases. In addition, removal of the stent was as simple as inserting it, and complications were absent. The stent introduced in this study could possibly be applied to various canine obstructive tracheal diseases.


Performance Improvement by Ozone Treatment of 2D PdSe2.
Atomic-scale defects in two-dimensional transition metal dichalcogenides (TMDs) often dominate their physical and chemical properties. Introducing defects in a controllable manner can tailor properties of TMDs. For example, chalcogen atom defects in TMDs were reported to trigger phase transition, induce ferromagnetism, and drive superconductivity. However, reported strategies to induce chalcogen atom defects including postgrowth annealing, laser irradiation, or plasma usually require high temperature (such as 500 °C) or cause unwanted structural damage. Here, we demonstrate low-temperature (60 °C) partial surface oxidation in 2D PdSe2 with low disorder and good stability. The combination of scanning tunneling microscopy, X-ray photoelectron spectroscopy, and density functional theory calculations provide evidence of atomic-scale partial oxidation with both atomic resolution and chemical sensitivity. We also experimentally demonstrate that this controllable oxygen incorporation effectively tailors the electronic, optoelectronic, and catalytic activity of PdSe2. This work provides a pathway toward fine-tuning the physical and chemical properties of 2D TMDs and their applications in nanoelectronics, optoelectronics, and electrocatalysis.


Working women's breastfeeding experiences.
To describe the breastfeeding experiences of women who returned to work after childbirth. Descriptive, using questionnaires with 50 women. Content analysis of data obtained from women who responded to open-ended questionnaires at 16 weeks postpartum. Three procedures were used: coding data, categorizing text units, and refining the emerging themes. Four categories emerged from the data:support, attitude, strategic plan, and psychological distress. The women expressed a need for support such as an accepting environment, spatial issues, modeling, and time allowance. They needed to maintain a positive attitude so they could commit to and accomplish their breastfeeding goals. The women developed strategic plans to help prevent breastfeeding problems as well as continue breastfeeding successfully. Finally, they described psychological distress as a conflict between the demands of work and the breastfeeding process. Associated feelings included guilt, stress, or having to sacrifice. These findings can help nurses and other healthcare professionals in providing anticipatory guidance to women who plan to continue breastfeeding after returning to work. Further research should investigate the relationship between psychological distress, work productivity, family functioning, and breastfeeding activities of working women who breastfeed.


The serine/threonine kinase cyclin G-associated kinase regulates epidermal growth factor receptor signaling.
Cyclin G-associated kinase (GAK) is a serine/threonine kinase that features high homology outside its kinase domain with auxilin. Like auxilin, GAK has been shown to be a cofactor for uncoating clathrin vesicles in vitro. We investigated epidermal growth factor (EGF) receptor-mediated signaling in cells, in which GAK is down-regulated by small hairpin RNAs. Here, we report that down-regulation of GAK by small hairpin RNA has two pronounced effects on EGF receptor signaling: (i) the levels of receptor expression and tyrosine kinase activity go up by >50-fold; and (ii) the spectrum of downstream signaling is significantly changed. One very obvious result is a large increase in the levels of activated extracellular signal-regulated kinase 5 and Akt. These two effects of GAK down-regulation result from, at least in part, alterations in receptor trafficking, the most striking of which is the persistence of EGF receptor in altered cellular compartment along with activated extracellular signal-regulated kinase 5. The alterations resulting from GAK down-regulation can have distinctive biological consequences: In CV1P cells, down-regulation of GAK results in outgrowth of cells in soft agar, raising the possibility that loss of GAK function may promote tumorigenesis.


Effectiveness of Parenteral Glutamine on Methotrexate-induced Oral Mucositis in Children with Acute Lymphoblastic Leukemia.
High-dose methotrexate (HDMTX) is important for children with acute lymphoblastic leukemia (ALL). There is no effective treatment for patients with oral mucositis, which is a major side effect associated with HDMTX. Here, we reviewed the medical records of patients younger than 18 yr with newly diagnosed ALL in our hospitals from 2002 to 2013. According to the nationwide protocol (TPOG-ALL-2002), each patient received four courses of HDMTX (2.5 or 5 g/m2) during consolidation therapy. HDMTX courses with glutamine therapy were as the glutamine group, and intravenous glutamine (0.4 g/kg/day) was started within 48 h after the initiation of HDMTX for 3 consecutive days. HDMTX courses without glutamine were as the control group. A total of 347 HDMTX courses were administrated in the 96 children with ALL during the study period. The incidence of oral mucositis was significantly lower in the glutamine group than in the control group (3.8% vs. 17.6%; P = 0.004). In the glutamine group, no patients suffered from severe oral mucositis. No severe adverse effects associated with glutamine administration were noted. Accordingly, parenteral glutamine appears to be feasible and safe to prevent oral mucositis in patients receiving HDMTX.


[Methicillin resistant yellow staphylococci].
The incidence of methicillin-resistant Staphylococcus aureus in Norway is extremely low. Isolation of such strains is nearly always associated with import. From December 1993 to January 1997 at the Ullevål University Hospital Department of Medical Microbiology, methicillin-resistant Staphylococcus aureus was isolated from 22 persons in Oslo (17 patients and five healthy carriers). A cluster of ten infected persons was detected (five patients and five carriers (nurses)) who were infected with strains showing an unusual antibiotic resistance pattern. All of the cluster strains except for beta-lactams were resistant to fucidic acid and sensitive to other antistaphylococcal agents. The cluster was associated with two hospitals. The five patients were all admitted to the same intensive care unit during the period May to July 1995. Four of the five patients (one died) were referred to the same department in a long-term care hospital for rehabilitation and training. Problems concerning epidemiological investigation and control are discussed.


Distribution of the two mating types among Histoplasma capsulatum isolates obtained from an urban histoplasmosis outbreak.
The mating type distribution among the 28 Histoplasma capsulatum isolates obtained from the histoplasmosis outbreaks which occurred in Indianapolis in 1978-1979 and 1980-1981 was studied. The overall ratio of + and - types was 1:2.5. The isolates from disseminated patients showed a 1(+):1(-) ratio while the isolates from non-disseminated pulmonary cases showed a 1(+):4(-) ratio. The frequency of the + type in these outbreaks was three times higher than that of the previous study. This was due to an unusually high prevalence of the + type among the patients with disseminated histoplasmosis.


Meal and beta-alanine coingestion enhances muscle carnosine loading.
Beta-alanine (BA) is a popular ergogenic supplement because it can induce muscle carnosine loading. We hypothesize that, by analogy with creatine supplementation, 1) an inverse relationship between urinary excretion and muscle loading is present, and 2) the latter is stimulated by carbohydrate- and protein-induced insulin action. In study A, the effect of a 5-wk slow-release BA (SRBA) supplementation (4.8 g · d(-1)) on whole body BA retention was determined in seven men. We further determined whether the coingestion of carbohydrates and proteins with SRBA would improve retention. In study B (34 subjects), we explored the effect of meal timing on muscle carnosine loading (3.2 g · d(-1) during 6-7 wk). One group received pure BA (PBA) in between the meals; the other received PBA at the start of the meals, to explore the effect of meal-induced insulin release. Further, we compared with a third group receiving SRBA at the start of the meals. Orally ingested SRBA has a very high whole body retention (97%-98%) that is not declining throughout the 5-wk supplementation period, nor is it influenced by the coingestion of macronutrients. Thus, a very small portion (1%-2%) is lost through urinary excretion, and equally only a small portion is incorporated into muscle carnosine (≈ 3%), indicating that most ingested BA is metabolized (possibly through oxidation). Second, in soleus muscles, the efficiency of carnosine loading is significantly higher when PBA is coingested with a meal (+64%) compared with in between the meals (+41%), suggesting that insulin stimulates muscle carnosine loading. Finally, the chronic supplementation of SRBA versus PBA seems equally effective.


Laparoscopic cholecystectomy in cirrhotics: a prospective randomized study comparing the conventional diathermy and the harmonic scalpel for gallbladder dissection.
Ultrasonically activated devices have been used for gallbladder dissection in laparoscopic cholecystectomy (LC) with encouraging results. The aim of the present study was to compare the surgical outcome of LC performed by the harmonic shears to that performed by the conventional diathermy in patients with cirrhosis. In this prospective randomized study, 40 cirrhotic Child-Pugh's classes A and B patients with symptomatic uncomplicated gallstones disease were randomly assigned to either the Harmonic scalpel LC group (20 patients) or the conventional diathermy LC group (20 patients). The use of the harmonic shears was associated with a statistically significant shorter median operative time (55 vs. 82.5 minutes, P = .000), less median estimated intraoperative blood loss (50 vs. 120 mL, P = .000), and lower incidence of gallbladder perforation (10% vs. 70%, P = .000). In the Harmonic scalpel LC group, Laparoscopic subtotal cholecystectomy was resorted to in eight patients (40%) compared with six patients (30%) in the conventional diathermy LC group. No statistically significant difference was found between both groups as regards the conversion rate, the median hospital stay, and the incidence of postoperative complications. Neither bile leaks nor Bile duct injuries were encountered in either group. Similarly, no mortalities were encountered in the present study. The Harmonic shears achieved complete hemobiliary stasis. Further, it provided a superior alternative to the conventional diathermy in terms of shorter operative time, less intraoperative blood loss, and lower incidence of gallbladder perforation partly through facilitating the performance of laparoscopic subtotal cholecystectomy.


Delayed surgical resection reduces intraoperative blood loss for embolized meningiomas.
Embolization before surgical resection of tumors has been demonstrated to reduce intraoperative blood loss, but the optimal time that should elapse between embolization and tumor resection has not been established. We evaluated whether immediate surgical resection (< or =24 h) after embolization or delayed surgical resection (>24 h) was more effective in minimizing intraoperative blood loss. We retrospectively analyzed the records for 50 patients with meningiomas who underwent preoperative embolization between 1993 and 1999. We divided the patients into two groups, i.e., those who underwent surgical resection of their meningiomas < or =24 hours after embolization and those who underwent surgery more than 24 hours after embolization. The extent of embolization, intraoperative blood loss, duration of surgery, and length of the hospital stay were compared for the two groups. Postoperative pathological specimens were examined for assessment of the extent of vascularity and necrosis caused by embolization. Intraoperative blood loss was greater for the immediate group than for the delayed group (29% with blood loss of >1000 ml [median, 475 ml] versus 0% with blood loss of >700 ml [median, 337.5 ml]; P = 0.01). There were no statistically significant differences between the groups with respect to tumor volume, extent of embolization, degree of devascularization, necrosis, duration of surgery, or length of the hospital stay. Contrary to previous studies that emphasized a need for tumor removal immediately after embolization, to prevent revascularization, surgical resection of meningiomas should be delayed more than 24 hours after embolization, because there is less intraoperative blood loss.


Rapid detection of anticardiolipin antibodies.
A rapid screening method for the detection of antiphospholipid antibodies is described. Dense, red dyed polystyrene beads coated with cardiolipin were incubated with test sera for a short period of time, then added to a microtube containing anti-human IgG in a gel provided within a pre-cast card (DiaMed ID Microtyping System). The card was centrifuged at 150g for 5 min and then examined for movement of the beads through the gel. Beads without bound antibody travelled through the gel and formed a pellet on the bottom of the tube. Anti-human IgG within the gel matrix impeded cardiolipin-coated beads when antiphospholipid antibodies bound to the beads. Positivity was indicated by the formation of a layer of beads on the top of the gel matrix. Prospective analysis of 103 samples for the presence of antiphospholipid antibodies by flow cytometry and the gel-card technique showed good correlation between the two methods. All samples found to be positive by flow cytometry (23 of 103) were identified as positive by the gel-card technique. Two samples were identified as positive by the gel-card method but negative by flow cytometry. The technique is simple to perform and should prove useful as a rapid screening method for the detection of antiphospholipid antibodies.