Modelling the Rayleigh match.
We use the photopigment template of Baylor et al. (1987) to define the set of Rayleigh matches that would be satisfied by a photopigment having a given wavelength of peak sensitivity (lambda(max)) and a given optical density (OD). For an observer with two photopigments in the region of the Rayleigh primaries, the observer's unique match is defined by the intersection of the sets of matches that satisfy the individual pigments. The use of a template allows us to illustrate the general behavior of Rayleigh matches as the absorption spectra of the underlying spectra are altered. In a plot of the Y setting against the red-green ratio (R), both an increase in lambda(max) and an increase in optical density lead to an anticlockwise rotation of the locus of the matches satisfied by a given pigment. Since both these factors affect the match, it is not possible to reverse the analysis and define uniquely the photopigments corresponding to a specific Rayleigh match. However, a way to constrain the set of candidate photopigments would be to determine the trajectory of the change of match as the effective optical density is altered (by, say, bleaching or field size).


Worms in Australia.
Fortunately, Australia does not have many of the parasitic worm infections, such as filariasis, onchocerciasis and dracunculiasis, that are important on a global scale. Nevertheless, several medically important parasitic worms are endemic in Australia. Intestinal nematodes occur mostly in the tropical north although threadworm is ubiquitous. Hydatid disease and tapeworm infections occur especially in sheep and cattle farming regions.


Effects of endosulfan pesticide on toad.
The lethal and sublethal toxicity of Endosulfan on the African toad, Bufo regularis were evaluated to assess changes in behaviour and energy reserves. 96 hours LC50 was 0.730 mg/l while the estimated safe concentration was 0.07 mg/L indicating the high toxicity of the insecticide. Toads exposed to lethal concentrations of endosulfan showed dose-dependent behavioural abnormalities with more pronounced poisoning symptoms occurring at higher concentrations. The pesticide caused differential increase in serum glucose levels with a concomitant reduction in liver glycogen indicating disorders in carbohydrate metabolism due to pesticide induced stress and hence can serve as suitable biomarkers in pesticide toxicity studies.


Effects of epidural infusion of morphine combined with small-dose naloxone on gastrointestinal interstitial cells of Cajal in rabbits.
To study the effect of epidural infusion of morphine combined with small-dose naloxone on gastrointestinal interstitial cells of Cajal (ICC) in rabbits. A total of 80 healthy New Zealand rabbits were selected as objects of study, and divided into normal saline control group (Group NS, n=20), morphine group (Group M, n=20), naloxone group (Group N, n=20), and morphine + naloxone group (Group NM, n=20). Rabbits in four the groups received epidural catheterization for continuous drug infusion for 7 d, and epidural analgesia pump was connected. Visual analogue scale (VAS) score, intestinal propulsion rate, c-kit expression, and ICC count were detected and compared among four groups of rabbits. No statistical differences of occurrence rates regarding constipation as well as expressions of c-kit and ICC count in the proximal colon were shown among rabbits in Group NS, Group N, and Group NM during drug administration (p>0.05). However, the occurrence rates of constipation of rabbits in Group M at 3-7 d were statistically higher than those in Group NS, Group N, and Group NM, and the differences were statistically significant (p<0.05). Moreover, the VAS scores in Group NS and Group N were significantly higher than those in Group M and Group NM, while the scores in Group M were also significantly increased compared to that in Group NM (p<0.05). The intestinal propulsion rates, expressions of c-kit and ICC counts of rabbits in Group NS, Group N, and Group NM were statistically higher than that in Group M (p<0.05). Epidural infusions of morphine combined with small-dose naloxone effectively inhibit the gastrointestinal motility of rabbits via the reduction of ICC in the proximal colon of the gastrointestinal tract of rabbits. Moreover, small-dose of naloxone enhances the analgesic effect and reduces the risk of adverse reactions.


Influence of endothelial mediators on the vascular smooth muscle and circulating platelets and blood cells.
The vascular endothelium regulates the tone of the underlying smooth muscle and the reactivity of blood elements such as platelets and neutrophils by the release of mediators, in particular nitric oxide, prostacyclin and endothelin-1. The first two of these are potent vasodilators which also inhibit platelet and neutrophil aggregation and adhesion, while endothelin-1 is the most potent mammalian vasoconstrictor peptite yet found. There are also interactions between these mediators. For instance, endothelin-1 acts on specific receptors on the endothelium to increase the release of nitric oxide and prostacyclin, while nitric oxide depresses the production and/or release of endothelin-1 from endothelial cells. Endothelin-1 and prostacyclin do not appear to be involved in the basal regulation of blood pressure whereas nitric oxide does for inhibition of its production in normotensive animals produces a marked elevation in blood pressure. Conversely, numerous vascular disease states have been associated with elevations in the production and/or release of endothelin-1 and it has been implicated in the deleterious changes associated with ischaemia/reperfusion injury, subarachnoid haemorrhage and hypertension. Endothelin-1 has also been proposed to be pro-atherogenic, as have reductions in the production of the vasodilator mediators nitric oxide and prostacyclin.


Restless leg syndrome frequency in health workers.
Introduction - Restless Leg Syndrome (RLS) is a disease, primarily composed of sensational symptoms, caused by the urge to move lower extremities especially at night, and characterized by undesired feelings of the legs. Decreasing of the dopaminergic effect at night is thought to be responsible from these symptoms. RLS patients suffer from low quality of sleep affecting their daily life activities even causing socio-economic loss. Although RLS is a common and treatable disease, it can not be diagnosed easily due to the variability of symptoms. Aim - The purpose of this study is to determine the frequency of RLS among health workers and to define the disease causing factors. Method - A questionnaire was applied to 174 randomly selected health workers at Baskent University Medical Faculty (KA17/285). The demographic information, history of illnesses or usage of drugs, socioeconomic status, working hours and daytime sleepiness were questioned. Included in the questionnaire were diagnostic criteria for RLS, frequency assessment scale, and survey of sleep quality. We used "the diagnostic criteria of international RLS working group" for the diagnosis, and "Pittsburgh sleep quality index survey" to determine the quality of sleep. Reliability and validity studies were performed on both tests. Results - A significant relationship between socio-economic status and RLS was found (p<0.05) as an increase of RLS frequency in parallel with decreased socio-economic status. RLS was found to be common among health workers. We suggest that health workers should be checked regularly, and they should be informed about the disease in order to raise an awareness and hence increase their quality of life.


Impact of Education and Data Feedback on Guideline-Concordant Prescribing for Urinary Tract Infections in the Outpatient Setting.
Urinary tract infections (UTIs) are the most common outpatient indication for antibiotics and an important target for antimicrobial stewardship (AS) activities. With The Joint Commission standards now requiring outpatient AS, data supporting effective strategies are needed. We conducted a 2-phase, prospective, quasi-experimental study to estimate the effect of an outpatient AS intervention on guideline-concordant antibiotic prescribing in a primary care (PC) clinic and an urgent care (UC) clinic between August 2017 and July 2019. Phase 1 of the intervention included the development of clinic-specific antibiograms and UTI diagnosis and treatment guidelines, presented during educational sessions with clinic providers. Phase 2, consisting of routine clinic- and provider-specific feedback, began ~12 months after the initial education. The primary outcome was percentage of encounters with first- or second-line antibiotics prescribed according to clinic-specific guidelines and was assessed using an interrupted time series approach. Data were collected on 4724 distinct patients seen during 6318 UTI encounters. The percentage of guideline-concordant prescribing increased by 22% (95% CI, 12% to 32%) after Phase 1 education, but decreased by 0.5% every 2 weeks afterwards (95% CI, -0.9% to 0%). Following routine data feedback in Phase 2, guideline concordance stabilized, and significant further decline was not seen (-0.6%; 95% CI, -1.6% to 0.4%). This shift in prescribing patterns resulted in a 52% decrease in fluoroquinolone use. Clinicians increased guideline-concordant prescribing, reduced UTI diagnoses, and limited use of high-collateral damage agents following this outpatient AS intervention. Routine data feedback was effective to maintain the response to the initial education.


The complete mitochondrial genome of Pontia edusa (Lepidoptera: Pieridae).
The complete mitochondrial genome of Pontia edusa was sequenced and analyzed in the study. The length of the complete mitogenome is 15,125 bp, including 37 genes and a control region. Twelve genes start with typical ATN, but COI gene initiate with a CGA codon. Twelve of 13 PCGs have a complete stop codon TAA or TAG except for COI has an incomplete stop codon T--. Twenty-one of the 22 tRNAs have a typical clover-leaf secondary structure. The tRNASer(AGN) gene lacked the DHU loop. Bayesian analyses highly support the monophyly of Pieridae. In Pieridae, P. edusa is subordinate to the Pierinae clade.


T cells traffic from brain to cervical lymph nodes via the cribroid plate and the nasal mucosa.
Although drainage pathways of soluble antigens from brain to cervical lymph nodes have been well established, there is no direct evidence for similar routes of leukocytes leaving the central nervous system. We developed a protocol allowing the cross-sectioning of an entire head-neck preparation while preserving the signal of the GFP. We monitored how GFP-expressing CD4 T lymphocytes injected into the entorhinal cortex after lesion or the lateral ventricle of unlesioned C57/bl6 mice reach cervical lymph nodes. Irrespective of the injection site, we demonstrate their passage through the cribroid plate, appearance in the nasal mucosa, and specific accumulation in one of the cervical lymph nodes.


Glycine at the NMDA receptor in cat visual cortex: saturation and changes with age.
1. Saturation of the glycine site at the N-methyl-D-aspartate (NMDA) receptor in cat visual cortex was tested by iontophoresing D-serine, and the contribution of this site to the visual response was tested by iontophoresing 7-chlorokynurenic acid (7-Cl-KYNA). Animals were tested at ages 3 wk, 6 wk, 5 mo, and adult. 2. In at least 40% of cells (24/57), D-serine increased the response significantly, showing that the glycine site was not saturated. However, the increase was rarely > 100%. 3. The amount by which D-serine increased the response did not vary significantly with age. 4. In five cases there was positive evidence for saturation of the glycine site. D-Serine did not increase the response significantly; however, when D-serine was applied on top of 7-Cl-KYNA, it did increase the response compared with that seen with 7-Cl-KYNA alone. These cases were all in 3-wk-old animals. In other cases (28/57), D-serine did not increase the response significantly, but we could not be absolutely certain that the D-serine had reached the site of action. 5. The effect of 7-Cl-KYNA was largest in 3-wk animals, in agreement with previous findings that the effect of D-2-amino-5-phosphonovalerate (APV) is largest at this age. 6. These results may provide a small part of the explanation for the finding that the NMDA receptor-mediated component of the visual response decreases between 3 and 6 wk of age, while the number of NMDA receptors is increasing. However, the magnitude of the results make it likely that other factors are more important.


Subcapsular double-J stent following ureteroscopy: unique complication.
Double-J (DJ) ureteral stent is a standard procedure in daily urological practice performed to relive ureteral obstruction or as a part of other endourological procedures. Although it is a common procedure, the widespread use of ureteral stents has corresponded to the increase in possible complication. We report a unique complication for a patient who presented with a renal subcapsular complete misplacement of DJ stent postureteroscopy for a distal ureteric stone. This challenging complication of ureteral stents is rare and organ threatening.


Biopsy of mammographically-detected breast lesions in a district hospital.
Seventy-nine consecutive needle localization biopsies were performed for non-palpable breast lesions discovered on screening mammography over a two-and-a-half-year period in a district hospital by 15 surgeons. Malignant disease was found in 24 biopsies (30%). Eight were in situ and 16 were infiltrative carcinomas. Half the cancers met the criteria of 'minimal' carcinoma as described by Gallagher and Martin. Forty percent of women 50 years and older (20 of 50) but only 13% of women less than 50 years (4 of 29) had a carcinoma. Of thirty-two mammograms read as 'probably' benign, two (6%) were malignant pathologically. Of forty-seven mammograms considered 'probably' malignant, 22 (47%) were malignant pathologically. Abnormal calcification (38%), density (34%) or both (28%) were suspicious mammographic features. All 'minimal' invasive carcinomas were associated with calcification. Complete removal of the lesion was not achieved in three cases (3.7%) of which none showed invasive malignancy. Of the seven complications, two required treatment. Localization biopsy of non-palpable breast lesions, detected by screening mammography in a district hospital, performed by general surgeons, has produced a yield of malignancies similar to that seen in more specialized units.


Siderophore-mediated iron acquisition influences motility and is required for full virulence of the xylem-dwelling bacterial phytopathogen Pantoea stewartii subsp. stewartii.
Iron is a key micronutrient for microbial growth but is often present in low concentrations or in biologically unavailable forms. Many microorganisms overcome this challenge by producing siderophores, which are ferric-iron chelating compounds that enable the solubilization and acquisition of iron in a bioactive form. Pantoea stewartii subsp. stewartii, the causal agent of Stewart's wilt of sweet corn, produces a siderophore under iron-limiting conditions. The proteins involved in the biosynthesis and export of this siderophore are encoded by the iucABCD-iutA operon, which is homologous to the aerobactin biosynthetic gene cluster found in a number of enteric pathogens. Mutations in iucA and iutA resulted in a decrease in surface-based motility that P. stewartii utilizes during the early stages of biofilm formation, indicating that active iron acquisition impacts surface motility for P. stewartii. Furthermore, bacterial movement in planta is also dependent on a functional siderophore biosynthesis and uptake pathway. Most notably, siderophore-mediated iron acquisition is required for full virulence in the sweet corn host, indicating that active iron acquisition is essential for pathogenic fitness for this important xylem-dwelling bacterial pathogen.


Spontaneous gastroesophageal reflux and airway patency during the night in adult asthmatics.
Controversies still exist on the role of nighttime gastroesophageal reflux (GER) in precipitating nocturnal asthma. We tested the relationship between GER and nocturnal bronchoconstriction by continuously and simultaneously monitoring both respiratory resistances and esophageal pH in seven asthmatics with moderate to severe GER disease. Twenty-nine GER episodes were found during the study night lasting more than 5 min (LGER) and 72 not longer than 5 min (SGER). Both long (LGER) and short (SGER) gastroesophageal refluxes were able to maintain significantly higher lower respiratory resistances (RLR) at the resolution of each GER episode (RLR(e)) with respect to baseline values. RLR, expressed as the area under the RLR curve along each GER episode (AUCR(LR)) and as RLR(e), showed significant correlations with GER duration. Moreover, a significant correlation was found between RLR measured 10 min after GER resolution and GER duration during each episode. We conclude that GER itself is able to elicit nocturnal bronchoconstriction in asthmatics with moderate to severe GER disease and that bronchoconstriction severity and duration are related to GER duration.


Differentiating benign and malignant pulmonary lesions with FDG-PET.
The purpose of this retrospective study was to evaluate the efficacy of positron emission tomography (PET) with 18F-fluoro-2-deoxyglucose (FDG) to differentiate benign from malignant pulmonary lesions. Fifty-five patients, suspected of having primary pulmonary neoplasm based on chest radiographic findings, underwent FDG-PET scanning. Pathological diagnoses were obtained in 41 patients with a total of 43 pulmonary lesions. The other 14 patients (14 lesions) were followed-up clinically for at least four months. The standard uptake value (SUV) was determined in each patient. The SUV of the 15 benign and 40 malignant pulmonary lesions were 1.60+/-0.42 and 6.14+/-2.67, respectively. If SUV was > 2.50, the pulmonary lesion was considered as a malignant pulmonary lesion. FDG-PET could correctly detect 34 true-positive and 15 true-negative pulmonary lesions. However, 6 false-positive and one-false negative pulmonary lesions were misdiagnosed by FDG-PET. The sensitivity, specificity and accuracy of FDG-PET to differentiate between benign and malignant pulmonary lesions were 94%, 71% and 86%, respectively. FDG-PET can accurately detect malignant pulmonary lesions with a high sensitivity. However, false-positive FDG-PET findings caused by some inflammatory processes may decrease its specificity.


Immunochemotherapy for visceral leishmaniasis: combinatorial action of Miltefosine plus LBSapMPL vaccine improves adaptative Th1 immune response with control of splenic parasitism in experimental hamster model.
The control of human visceral leishmaniasis (VL) is hard since there are no vaccines available as well as the treatment is hampered by toxicity and resistant parasites. Furthermore, as human, and canine VL causes immunosuppression, the combination of drugs with immunostimulatory agents is interesting to upregulate the immunity, reducing side-effects, improving treatment approaches against disease. Herein, we assessed the immunochemotherapy using miltefosine along with a vaccine formulated by Leishmania braziliensis antigens + saponin + monophosphoryl lipid-A (LBSapMPL) in L. infantum-infected hamsters. Two months after infection, the animals received treatments, and after 15 days they were evaluated for the treatment effect. The potential anti-Leishmania effect of miltefosine + LBSapMPL-vaccine was revealed by a specific immune response activation reflecting in control of spleen parasitism using half the miltefosine treatment time. The treated animals also showed an increase of total and T-CD4 splenocytes producing IFN-γ and TNF-α and a decrease of interleukin-10 and anti-Leishmania circulating IgG. In addition, it was demonstrated that the control of spleen parasitism is related to the generation of a protective Th1 immune response. Hence, due to the combinatorial action of miltefosine with LBSapMPL-vaccine in immunostimulating and controlling parasitism, this immunochemotherapy protocol can be an important alternative option against canine and human VL.


Pop-In Identification in Nanoindentation Curves with Deep Learning Algorithms.
High-speed nanoindentation rapidly generates large datasets, opening the door for advanced data analysis methods such as the resources available in artificial intelligence. The present study addresses the problem of differentiating load-displacement curves presenting pop-in, slope changes, or instabilities from curves exhibiting a typical loading path in large nanoindentation datasets. Classification of the curves was achieved with a deep learning model, specifically, a convolutional neural network (CNN) model implemented in Python using TensorFlow and Keras libraries. Load-displacement curves (with pop-in and without pop-in) from various materials were input to train and validate the model. The curves were converted into square matrices (50 × 50) and then used as inputs for the CNN model. The model successfully differentiated between pop-in and non-pop-in curves with approximately 93% accuracy in the training and validation datasets, indicating that the risk of overfitting the model was negligible. These results confirmed that artificial intelligence and computer vision models represent a powerful tool for analyzing nanoindentation data.


Incorporating a guanidine-modified cytosine base into triplex-forming PNAs for the recognition of a C-G pyrimidine-purine inversion site of an RNA duplex.
RNA duplex regions are often involved in tertiary interactions and protein binding and thus there is great potential in developing ligands that sequence-specifically bind to RNA duplexes. We have developed a convenient synthesis method for a modified peptide nucleic acid (PNA) monomer with a guanidine-modified 5-methyl cytosine base. We demonstrated by gel electrophoresis, fluorescence and thermal melting experiments that short PNAs incorporating the modified residue show high binding affinity and sequence specificity in the recognition of an RNA duplex containing an internal inverted Watson-Crick C-G base pair. Remarkably, the relatively short PNAs show no appreciable binding to DNA duplexes or single-stranded RNAs. The attached guanidine group stabilizes the base triple through hydrogen bonding with the G base in a C-G pair. Selective binding towards an RNA duplex over a single-stranded RNA can be rationalized by the fact that alkylation of the amine of a 5-methyl C base blocks the Watson-Crick edge. PNAs incorporating multiple guanidine-modified cytosine residues are able to enter HeLa cells without any transfection agent.


Mechanistic aspects of hSOD1 maturation from the solution structure of Cu(I) -loaded hCCS domain 1 and analysis of disulfide-free hSOD1 mutants.
Superoxide dismutase 1 (SOD1) maturation within the cell is mainly accomplished with the SOD1-specific chaperone, CCS, a dimeric protein with three distinct domains in each monomer. We recently showed that the first domain of human CCS (hCCSD1) is responsible for copper transfer to its protein partner, human SOD1 (hSOD1). The NMR solution structure of the copper(I)-loaded form of hCCSD1 reported here contributes further to characterization of the copper-transfer mechanism to hSOD1. NMR spectroscopy was also used to examine the hSOD1 mutants C57A, C146A, and C57A/C146A, which are unable to form the structurally conserved disulfide bond in SOD1, in order to investigate the role of these cysteines during hSOD1 copper acquisition. Together, the information on both hCCS and hSOD1, along with a sequence analysis of eukaryotic CCSD1, allows us to propose important mechanistic aspects regarding the copper-transfer process from hCCS to hSOD1.


Laparoscopic surgery for endometriosis.
Endometriosis is associated with pain and infertility. Surgical interventions aim to remove visible areas of endometriosis and restore the anatomy. To assess the effectiveness and safety of laparoscopic surgery in the treatment of pain and infertility associated with endometriosis. This review has drawn on the search strategy developed by the Cochrane Gynaecology and Fertility Group including searching the Cochrane Gynaecology and Fertility Group's specialised register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, reference lists for relevant trials, and trial registries from inception to April 2020. We selected randomised controlled trials (RCTs) that compared the effectiveness and safety of laparoscopic surgery with any other laparoscopic or robotic intervention, holistic or medical treatment, or diagnostic laparoscopy only. Two review authors independently performed selection of studies, assessment of trial quality and extraction of relevant data with disagreements resolved by a third review author. We collected data for the core outcome set for endometriosis. Primary outcomes included overall pain and live birth. We evaluated the quality of evidence using GRADE methods. We included 14 RCTs. The studies randomised 1563 women with endometriosis. Four RCTs compared laparoscopic ablation or excision with diagnostic laparoscopy only. Two RCTs compared laparoscopic excision with diagnostic laparoscopy only. One RCT compared laparoscopic ablation or excision with laparoscopic ablation or excision and uterine suspension. Two RCTs compared laparoscopic ablation and uterine nerve transection with diagnostic laparoscopy only. One RCT compared laparoscopic ablation with diagnostic laparoscopy and gonadotropin-releasing hormone (GnRH) analogues. Two RCTs compared laparoscopic ablation with laparoscopic excision. One RCT compared laparoscopic ablation or excision with helium thermal coagulator with laparoscopic ablation or excision with electrodiathermy. One RCT compared conservative laparoscopic surgery with laparoscopic colorectal resection of deep endometriosis infiltrating the rectum. Common limitations in the primary studies included lack of clearly described blinding, failure to fully describe methods of randomisation and allocation concealment, and poor reporting of outcome data. Laparoscopic treatment versus diagnostic laparoscopy We are uncertain of the effect of laparoscopic treatment on overall pain scores compared to diagnostic laparoscopy only at six months (mean difference (MD) 0.90, 95% confidence interval (CI) 0.31 to 1.49; 1 RCT, 16 participants; very low quality evidence) and at 12 months (MD 1.65, 95% CI 1.11 to 2.19; 1 RCT, 16 participants; very low quality evidence), where a positive value means pain relief (the higher the score, the more pain relief) and a negative value reflects pain increase (the lower the score, the worse the increase in pain). No studies looked at live birth. We are uncertain of the effect of laparoscopic treatment on quality of life compared to diagnostic laparoscopy only: EuroQol-5D index summary at six months (MD 0.03, 95% CI -0.12 to 0.18; 1 RCT, 39 participants; low quality evidence), 12-item Short Form (SF-12) mental health component (MD 2.30, 95% CI -4.50 to 9.10; 1 RCT, 39 participants; low quality evidence) and SF-12 physical health component (MD 2.70, 95% CI -2.90 to 8.30; 1 RCT, 39 participants; low quality evidence). Laparoscopic treatment probably improves viable intrauterine pregnancy rate compared to diagnostic laparoscopy only (odds ratio (OR) 1.89, 95% CI 1.25 to 2.86; 3 RCTs, 528 participants; I2 = 0%; moderate quality evidence). We are uncertain of the effect of laparoscopic treatment compared to diagnostic laparoscopy only on ectopic pregnancy (MD 1.18, 95% CI 0.10 to 13.48; 1 RCT, 100 participants; low quality evidence) and miscarriage (MD 0.94, 95% CI 0.35 to 2.54; 2 RCTs, 112 participants; low quality evidence). There was limited reporting of adverse events. No conversions to laparotomy were reported in both groups (1 RCT, 341 participants). Laparoscopic ablation and uterine nerve transection versus diagnostic laparoscopy We are uncertain of the effect of laparoscopic ablation and uterine nerve transection on adverse events (more specifically vascular injury) compared to diagnostic laparoscopy only (OR 0.33, 95% CI 0.01 to 8.32; 1 RCT, 141 participants; low quality evidence). No studies looked at overall pain scores (at six and 12 months), live birth, quality of life, viable intrauterine pregnancy confirmed by ultrasound, ectopic pregnancy and miscarriage. Laparoscopic ablation versus laparoscopic excision There was insufficient evidence to determine whether there was a difference in overall pain, measured at 12 months, for laparoscopic ablation compared with laparoscopic excision (MD 0.00, 95% CI -1.22 to 1.22; 1 RCT, 103 participants; very low quality evidence). No studies looked at overall pain scores at six months, live birth, quality of life, viable intrauterine pregnancy confirmed by ultrasound, ectopic pregnancy, miscarriage and adverse events. Helium thermal coagulator versus electrodiathermy We are uncertain whether helium thermal coagulator compared to electrodiathermy improves quality of life using the 30-item Endometriosis Health Profile (EHP-30) at nine months, when considering the components: pain (MD 6.68, 95% CI -3.07 to 16.43; 1 RCT, 119 participants; very low quality evidence), control and powerlessness (MD 4.79, 95% CI -6.92 to 16.50; 1 RCT, 119 participants; very low quality evidence), emotional well-being (MD 6.17, 95% CI -3.95 to 16.29; 1 RCT, 119 participants; very low quality evidence) and social support (MD 5.62, 95% CI -6.21 to 17.45; 1 RCT, 119 participants; very low quality evidence). Adverse events were not estimable. No studies looked at overall pain scores (at six and 12 months), live birth, viable intrauterine pregnancy confirmed by ultrasound, ectopic pregnancy and miscarriage. Compared to diagnostic laparoscopy only, it is uncertain whether laparoscopic surgery reduces overall pain associated with minimal to severe endometriosis. No data were reported on live birth. There is moderate quality evidence that laparoscopic surgery increases viable intrauterine pregnancy rates confirmed by ultrasound compared to diagnostic laparoscopy only. No studies were found that looked at live birth for any of the comparisons. Further research is needed considering the management of different subtypes of endometriosis and comparing laparoscopic interventions with lifestyle and medical interventions. There was insufficient evidence on adverse events to allow any conclusions to be drawn regarding safety.


HLA-DQB1*0201: a marker for good prognosis in British and Dutch patients with sarcoidosis.
Human leukocyte antigen (HLA)-DQB1 is one of the intriguing candidate genes in sarcoidosis. We performed high resolution molecular HLA-DQB1 typing on two groups of white patients (British [UK] and Dutch [NL]) in order to investigate the relationship between 19 DQB1 alleles and disease severity and progression. A total of 803 individuals were studied (133 UK and 102 NL patients, and 354 UK and 214 NL control subjects). Disease severity data included extrapulmonary disease, chest X-ray stage, lung diffusing capacity for carbon monoxide, and FVC. Progression was evaluated on follow-up chest radiographs (2 and 4 yr). The results showed DQB1*0201 to be strongly protective against severe sarcoidosis in both populations; in other words, it localized to Stage I at all time points (P < 0.0001, P(corrected) (P(c)) = 0.002), whereas another DQB1 allele, *0602, tended to have opposite effects. Further, a clear association was found between the *0201 allele and Löfgren's syndrome (P < 0.0001, P(c) = 0.001). More importantly, carriage of this allele reduced the risk of disease progression. In contrast, the other common split of DQB1*02, *0202, did not affect disease severity but was mildly protective against sarcoidosis in the UK population (P = 0.02, p(c) not significant). In conclusion, this study shows that DQB1*0201 is a strong marker for mild sarcoidosis. Additional mapping across the DQB1*0201-DRB1*0301 haplotype, including specific alleles at genes such as DRB3, tumor necrosis factor, lymphotoxin-alpha, I-kappa-B-like protein, and B-associated transcript 1, is necessary for a final localization of the protective effect on this haplotype.


Ticlopidine-induced aplastic anemia and quick recovery with G-CSF: case report and literature review.
We report here a case of ticlopidine-induced aplastic anemia that responded to G-CSF and review the literature. An 83-year-old woman was started on ticlopidine for coronary artery disease after an episode of upper gastrointestinal bleeding secondary to aspirin. She developed aplastic anemia seven weeks after initiation of ticlopidine. She was hospitalised and received empiric antibiotic therapy and granulocyte colony stimulating factor (G-CSF). Her bone marrow started to recover quickly, and white blood cell and platelet counts returned to normal within three weeks. A review of medical literature revealed 20 similar cases of ticlopidine-induced aplastic anemia resulting in death in seven cases. G-CSF has been used previously with variable success. Ticlopidine is associated with serious, sometimes fatal hematological side effects. This risk should be seriously taken into consideration when prescribing ticlopidine. G-CSF may be helpful in the treatment of ticlopidine-induced aplastic anemia.


Cumulative Live Birth Rates Following Stimulation With Corifollitropin Alfa Compared With hp-hMG in a GnRH Antagonist Protocol in Poor Ovarian Responders.
Background: Bologna criteria poor ovarian responders have a very low prognosis. Although, it has been proposed that LH supplementation could be beneficial in women with previous hypo-response to FSH. There are no studies comparing the cumulative live birth rates (LBRs) between corifollitropin alfa (CFA) and highly purified human menopausal gonadotrophin (hp-hMG). Objective: To compare cumulative LBRs in Bologna poor ovarian responders undergoing ovarian stimulation with CFA followed by hp-hMG vs. hp-hMG alone in a GnRH antagonist protocol. Design: This is a retrospective cohort study. We included in total 917 poor responders fulfilling the Bologna criteria for poor ovarian response (POR) at a university-affiliated tertiary center from January 2011 until March 2017. Patients were administered either fixed daily doses of 300-450 IU of hp-hMG (group A) or a single dose of 150 μg of CFA followed by daily injections of ≥300 IU of hp-hMG from Day 8 of stimulation until the day of ovulation trigger (group B), in a fixed GnRH antagonist protocol. Results: LBRs after fresh embryo transfer (ET) were similar in group A 71/510 (14%) and B 42/407 (10%). Cumulative LBR per cycle was significantly higher in group A (16.9%) compared to group B (11.8%); (P = 0.03). However, logistic regression analysis showed no association between the type of gonadotropin administered and cumulative LBR. Only age was significantly associated with cumulative LBR (OR = 0.93, P = 0.007). Conclusion: Cumulative LBRs are similar in Bologna poor responders stimulated with CFA followed by hp-hMG compared to hp-hMG monotreatment in an antagonist protocol.


Gestational diabetes mellitus and neonatal hyperthyrotropinemia.
To determine whether gestational diabetes mellitus (GDM) is associated with increased incidence of neonatal hyperthyrotropinemia. In a retrospective study, maternal characteristics, infant outcome and cord blood thyrotropin (TSH) concentration were compared between 469 diet-treated GDM pregnancies diagnosed by the World Health Organization 75 g oral glucose tolerance test (OGTT) with 474 non-diabetic pregnancies with normal OGTT results. Hyperthyrotropinemia (TSH >16 mIU/l) was found in 7.2% of the GDM pregnancies and 2.1% of the controls (p < 0.001), but there was no difference in the birth weight or gestational age. The TSH concentration was correlated with the OGTT 2-hour glucose value (rho = 0.0948, p = 0.029) and Apgar score at the fifth minute (rho = -0.1197, p = 0.009). There was no difference in the TSH or free thyroxine concentrations between the hyperthyrotropinemic newborns of the GDM and control groups. In the GDM group, the hyperthyrotropinemic newborns had a higher incidence (p = 0.017) of neonatal jaundice. Neonatal hyperthyrotropinemia is more frequently found in pregnancies with GDM, and this could have reflected increased fetal in-utero hypoxic stress in these pregnancies.


Standard-dose and high-dose daily antiviral therapy for short episodes of genital HSV-2 reactivation: three randomised, open-label, cross-over trials.
Skin and mucosal herpes simplex virus type 2 (HSV-2) shedding predominantly occurs in short subclinical episodes. We assessed whether standard-dose or high-dose antiviral therapy reduces the frequency of such shedding. HSV-2-seropositive, HIV-seronegative people were enrolled at the University of Washington Virology Research Clinic (WA, USA). We did three separate but complementary open-label cross-over studies comparing no medication with aciclovir 400 mg twice daily (standard-dose aciclovir), valaciclovir 500 mg daily (standard-dose valaciclovir) with aciclovir 800 mg three times daily (high-dose aciclovir), and standard-dose valaciclovir with valaciclovir 1 g three times daily (high-dose valaciclovir). The allocation sequence was generated by a random number generator. Study drugs were supplied in identical, numbered, sealed boxes. Study periods lasted 4-7 weeks, separated by 1 week wash-out. Participants collected genital swabs four times daily for quantitative HSV DNA PCR. Clinical data were masked from laboratory personnel. The primary endpoint was within-person comparison of shedding rate in each study group. Analysis was per protocol. The trials are registered at ClinicalTrials.gov (NCT00362297, NCT00723229, NCT01346475). Of 113 participants randomised, 90 were eligible for analysis of the primary endpoint. Participants collected 23 605 swabs; 1272 (5·4%) were HSV-positive. The frequency of HSV shedding was significantly higher in the no medication group (n=384, 18·1% of swabs) than in the standard-dose aciclovir group (25, 1·2%; incidence rate ratio [IRR] 0·05, 95% CI 0·03-0·08). High-dose aciclovir was associated with less shedding than standard-dose valaciclovir (198 [4·2%] vs 209 [4·5%]; IRR 0·79, 95% CI 0·63-1·00). Shedding was less frequent in the high-dose valaciclovir group than in the standard-dose valaciclovir group (164 [3·3%] vs 292 [5·8%]; 0·54, 0·44-0·66). The number of episodes per person-year did not differ significantly for standard-dose valaciclovir (22·6) versus high-dose aciclovir (20·2; p=0·54), and standard-dose valaciclovir (14·9) versus high-dose valaciclovir (16·5; p=0·34), but did for no medication (28·7) and standard-dose aciclovir (10·0; p=0·001). Median episode duration was longer for no medication than for standard-dose aciclovir (13 h vs 7 h; p=0·01) and for standard-dose valaciclovir than for high-dose valaciclovir (10 h vs 7 h; p=0·03), but did not differ significantly between standard-dose valaciclovir and high-dose aciclovir (8 h vs 8 h; p=0·23). Likewise, maximum log(10) copies of HSV detected per mL was higher for no medication than for standard dose aciclovir (3·3 vs 2·9; p=0·02), and for standard-dose valaciclovir than for high-dose valaciclovir (2·5 vs 3·0; p=0·001), but no significant difference was recorded for standard-dose valaciclovir versus high-dose aciclovir (2·7 vs 2·8; p=0·66). 80% of episodes were subclinical in all study groups. Except for a higher frequency of headaches with high-dose valaciclovir (n=13, 30%) than with other regimens, all regimens were well tolerated. Short bursts of subclinical genital HSV reactivation are frequent, even during high-dose antiherpes therapy, and probably account for continued transmission of HSV during suppressive antiviral therapy. More potent antiviral therapy is needed to eliminate HSV transmission. NIH. Valaciclovir was provided for trial 3 for free by GlaxoSmithKline.


Plasmids for nicotine-dependent and -independent gene expression in Arthrobacter nicotinovorans and other arthrobacter species.
The first inducible Arthrobacter overexpression system, based on the promoter/operator and the repressor of the 6-D-hydroxynicotine oxidase gene of Arthrobacter nicotinovorans, is described here. Nicotine-dependent overproduction and affinity purification of recombinant proteins are presented. The system will allow the production of complex enzymes and genetic complementation studies in Arthrobacter species.


Effect of Local Infiltration Analgesia on Functional Outcomes in Total Knee Arthroplasty: A Randomized, Placebo-Controlled, Double-Blind Clinical Trial.
Local infiltration analgesia (LIA) is a simple, surgeon-administered technique for the treatment of postoperative pain after total knee arthroplasty (TKA). The aim of the study was to investigate the efficacy of LIA and its effects on functional outcomes in TKA. A total of 135 patients with primary TKA were recruited and randomized either to receive LIA or to receive placebo injection (PI). Pain, active range of motion (ROM), knee function score, functional activities, and hospital length of stay (LOS) were assessed before surgery and from postoperative day (POD) 1 to at discharge. Lower pain scores at rest were recorded on POD1 and POD2 in the LIA group (p = 0.027 and p = 0.020, respectively). Lower pain score on walking was recorded on POD1 in the LIA group (p = 0.002). There was a statistically significant difference in active knee flexion between groups on POD1 (p = 0.038). There was a significant difference in LOS between LIA and PI groups. Shorter stay was seen in LIA group. There were no statistically significant differences between the groups in terms of knee function score and functional outcomes. LIA technique is effective for pain management in the early postoperative period. LIA added benefit for knee function in terms of active knee flexion ROM after TKA. A shorter hospital LOS was observed in LIA group. However, we did not find any differences in groups in terms of functional assessment such as ability to rise from a chair and walking capacity.The level of evidence is randomized controlled trial, level I.


Clinical Correlation Between Overactive Bladder and Allergy in Children.
The International Children's Continence Society defines overactive bladder (OAB) as a clinical syndrome characterized by urgency of urination usually accompanied by frequent urination and nocturia symptoms. This study aims to explore the correlation between overactive bladder (OAB) and allergy in children. The clinical characteristics of 918 patients diagnosed with OAB from January 2020 to March 2021 were retrospectively analyzed. Risk factors for OAB were analyzed using logistic regression analysis, and the effect of desloratadine in the treatment of OAB was evaluated. The incidence of allergic cough or allergic rhinitis in the mild OAB group was higher than the moderate-severe group. Urodynamics demonstrated that the proportion of patients with a sensitive bladder in the overactive detrusor group was significantly higher than the non-overactive detrusor group. The effective rate of treatment of OAB in patients complicated with allergies and taking desloratadine was 90.14%, which was significantly higher than in patients who were not taking desloratadine, and blood IgE level was a risk factor of ineffective treatment with desloratadine. OAB is correlated with allergies in children, and desloratadine can effectively improve OAB symptoms.


Methyllithium-Doped Naphthyl-Containing Conjugated Microporous Polymer with Enhanced Hydrogen Storage Performance.
Hydrogen storage is a primary challenge for using hydrogen as a fuel. With ideal hydrogen storage kinetics, the weak binding strength of hydrogen to sorbents is the key barrier to obtain decent hydrogen storage performance. Here, we reported the rational synthesis of a methyllithium-doped naphthyl-containing conjugated microporous polymer with exceptional binding strength of hydrogen to the polymer guided by theoretical simulations. Meanwhile, the experimental results showed that isosteric heat can reach up to 8.4 kJ mol(-1) and the methyllithium-doped naphthyl-containing conjugated microporous polymer exhibited an enhanced hydrogen storage performance with 150 % enhancement compared with its counterpart naphthyl-containing conjugated microporous polymer. These results indicate that this strategy provides a direction for design and synthesis of new materials that meet the US Department of Energy (DOE) hydrogen storage target.


E-cigarette or vaping induced lung injury: A case series and literature review.
Recently, a rapidly increasing number of e-cigarette or vaping induced lung injury (EVALI) has been reported across the nation. Given the ongoing epidemic, it has been suggested that specific chemical substances used as additives in e-cigarettes could be highly related to EVALI. A history of vaping with positive radiographic changes and low suspicion for active infection are requirements for diagnosis but it still remains a diagnosis of exclusion. The course of the disease, mechanism of lung injury and the optimal management options need to be better understood. Here we aimed to discuss the clinical characteristics recognized in a case series of ten hospitalized EVALI patients with radiological findings of lung injury and provide an up today summary of the known literature of EVALI-induced lung injury. A retrospective chart review was conducted on ten patients who presented to Saint Peter's University Hospital in New Brunswick, NJ from July 2019 to February 2020, with a mean hospital stay of five days. According to the CDC recommended definition of the disease, our cases met the current working definition of confirmed or probable cases of EVALI. Ten patients, with mean age 30.8 years (50 % male) and average years of vaping 1.708 with 60 % endorsing a simultaneous history of cannabis-related products use, went under a retrospective review. 3/10 (30 %) had documented medically-managed pulmonary disease history, 8/10 (80 %) presented with the respiratory-related chief complaint, 6/10 (60 %) presented with gastrointestinal symptoms and 7/10 (70 %) had constitutional symptoms. All patients (100 %) were found to have bilateral ground-glass opacities on chest imaging. 9/10 were admitted, 6/10 (60 %) had an oxygen saturation of <95 % requiring oxygen supplementation with 4/10 managed in the intensive care unit. EVALI patients with radiological findings of lung injury, although mainly present respiratory symptoms, may very often appear with constitutional and gastrointestinal symptoms. Based on the existing literature and our data it is argued that EVALI may be misdiagnosed and that closer monitoring is required to determine optimal diagnostic and therapeutic management of this condition. Our data and the existing literature suggest that laboratory and epidemiologic findings can be contributory for the diagnosis of the disease.


[Study of anti-amnesic activity of amiridin in a model of amnesic syndrome].
The model of amnestic syndrome obtained by treatment with scopolamine during 20 days in rats was used to study anti-amnesic activity of amiridin in comparison with that of tacrine, physostigmine and piracetam. Multiple injection of Sc resulted in significant deterioration of rats, performance in passive avoidance test. Behavioral disorders were accompanied by such changes in lipid composition of brain synaptosomes which indicated a decreased membrane fluidity. Amiridin and tacrine as well as piracetam showed anti-amnesic action which in the course of treatment correlated with their normalizing effect on lipid content of synaptosomes. The diverse effect of amiridin and tacrine with respect to physostigmine implies that the former drugs can't be attributed to anticholinesterase preparations which are traditionally used in the treatment of Alzheimer disease.


Immunoreactive estrogen receptor protein in meningiomas: comparison with the androgen receptor and progesterone receptor binding activity.
Analyses of gonadal steroid hormone receptor were performed using a monoclonal enzyme immunoassay for human estrogen receptor protein (estrophilin) for the first time and a conventional radioligand binding technique for progesterone and androgen receptors in 70 meningiomas. Low levels of estrogen receptor immunoreactivity (3.7 +/- 0.5 fmol/mg protein) were detected in 37 (53%) tumors, whereas moderate concentrations of androgen receptor binding activity (31.7 +/- 5.3 fmol/mg protein) and high concentrations of progesterone receptor binding activity (189 +/- 29.2 fmol/g protein) were demonstrated in 33 (47%) and 53 (76%) tumors, respectively. The estrophilin immunoreactivity was positively correlated with the androgen receptor binding activity (r = 0.634; p less than 0.001) but no relationship with the progesterone receptor binding activity was found. The presence of gonadal steroid receptors in a large proportion of meningiomas could have implications for diagnosis and tumor therapy.


Peripheral vascular injuries from plastic bullets in children.
During an eight month interval, 15 children and adolescents less than 20 years of age sustained vascular injuries to the lower extremities from plastic bullets. The plastic bullets had been introduced by the authorities as an attempt to reduce mortality from clashes between soldiers and demonstrators. Twenty-three vessels were injured in these 15 children: four patients had isolated arterial injuries, three had isolated venous injuries, and eight had combined injuries. The arterial injuries were repaired primarily or with reversed saphenous vein interposition grafts. The limb salvage rate was 100 percent, and there were no deaths. Eighty percent of the patients had palpable distal pulses observed at follow-up examination. We conclude from this experience that plastic bullets can cause serious injuries in children, vascular injuries from gunshots in children should be repaired or reconstructed using techniques perfected in the adult population, and low velocity gunshot vascular injuries in the pediatric age group can be successfully treated in a minimally equipped, developing world hospital by well-trained general surgeons.


Changes in P3b Latency and Amplitude Reflect Expertise Acquisition in a Football Visuomotor Learning Task.
Learning is not a unitary phenomenon. Rather, learning progresses through stages, with the stages reflecting different challenges that require the support of specific cognitive processes that reflect the functions of different brain networks. A theory of general learning proposes that learning can be divided into early and late stages controlled by corticolimbic networks located in frontal and posterior brain regions, respectively. Recent human studies using dense-array EEG (dEEG) support these results by showing progressive increases in P3b amplitude (an Event Related Potential with estimated sources in posterior cingulate cortex and hippocampus) as participants acquire a new visuomotor skill. In the present study, the P3b was used to track the learning and performance of participants as they identify defensive football formations and make an appropriate response. Participants acquired the task over three days, and P3b latency and amplitude significantly changed when participants learned the task. As participants demonstrated further proficiency with extensive training, amplitude and latency changes in the P3b continued to closely mirror performance improvements. Source localization results across all days suggest that an important source generator of the P3b is located in the posterior cingulate cortex. Results from the study support prior findings and further suggest that the careful analysis of covert learning mechanisms and their underlying electrical signatures are a robust index of task competency.


Role of Side-Chain Molecular Features in Tuning Lower Critical Solution Temperatures (LCSTs) of Oligoethylene Glycol Modified Polypeptides.
A series of thermoresponsive polypeptides has been synthesized using a methodology that allowed facile adjustment of side-chain functional groups. The lower critical solution temperature (LCST) properties of these polymers in water were then evaluated relative to systematic molecular modifications in their side-chains. It was found that in addition to the number of ethylene glycol repeats in the side-chains, terminal and linker groups also have substantial and predictable effects on cloud point temperatures (Tcp). In particular, we found that the structure of these polypeptides allowed for inclusion of polar hydroxyl groups, which significantly increased their hydrophilicity and decreased the need to use long oligoethylene glycol repeats to obtain LCSTs. The thioether linkages in these polypeptides were found to provide an additional structural feature for reversible switching of both polypeptide conformation and thermoresponsive properties.


Systematic approach to celiac disease: a comprehensive review for primary providers.
Celiac disease is an immune-mediated illness to gluten exposure in genetically susceptible patients. It is characterized by chronic lymphocytic inflammation of the small bowel leading to villous atrophy and its associated complications. The global prevalence of celiac disease is increasing, due in part to improved screening tests and simplified diagnostic criteria. Novel therapies are being developed and include proteolytic enzymes, sequestering agents, and immunotherapies. A strict gluten-free diet, however, remains the mainstay of treatment. In this comprehensive review, we discuss the epidemiology, definitions, diagnosis, and treatment of celiac disease.


Umbilical Cord Management for Newborns <34 Weeks' Gestation: A Meta-analysis.
The International Liaison Committee on Resuscitation prioritized scientific review of umbilical cord management strategies at preterm birth. To determine the effects of umbilical cord management strategies (including timing of cord clamping and cord milking) in preterm infants <34 weeks' gestation. Cochrane Central Register of Controlled Trials, Medline, PubMed, Embase, CINAHL, and trial registries were searched through July 2019 for randomized controlled trials assessing timing of cord clamping and/or cord milking. Two authors independently assessed trial eligibility, extracted data, appraised risk of bias, and assessed evidence certainty (GRADE). We identified 42 randomized controlled trials (including 5772 infants) investigating 4 different comparisons of cord management interventions. Compared to early cord clamping, delayed cord clamping (DCC) and intact-cord milking (ICM) may slightly improve survival; however, both are compatible with no effect (DCC: risk ratio: 1.02, 95% confidence interval: 1.00 to 1.04, n = 2988 infants, moderate certainty evidence; ICM: risk ratio: 1.02, 95% confidence interval: 0.98 to 1.06, n = 945 infants, moderate certainty evidence). DCC and ICM both probably improve hematologic measures but may not affect major neonatal morbidities. For many of the included comparisons and outcomes, certainty of evidence was low. Our subgroup analyses were limited by few researchers reporting subgroup data. DCC appears to be associated with some benefit for infants born <34 weeks. Cord milking needs further evidence to determine potential benefits or harms. The ideal cord management strategy for preterm infants is still unknown, but early clamping may be harmful.


[Rural emigration in the inter-Andean valleys of Bolivia].
"Inscribed within an ancient national tradition, rural emigration in the interandean valleys of Bolivia is gaining importance. The country's contemporary crises and the immigration policies of the host countries maintain the flux trend towards Argentina while enabling new destination targets: the United States, and more recently Israel and Japan. In these Bolivian lands, the emigration derived income provides the driving force of family economies and triggers development of the local territory. At the same time, emigration induces a process of socio-economic differentiation in peasant communities which weakens the food-system and increases family nutritional risks in the populations marginal to this migration system. In addition to these mutations there is a strong sociocultural destructuring which affects community-cohesion in local societies." (SUMMARY IN ENG AND SPA)


Preventing adhesions in obstetric and gynecologic surgical procedures.
Adhesive disease represents a significant cause of morbidity for postoperative patients. Most surgical procedures performed by obstetrician-gynecologists are associated with pelvic adhesions that cause subsequent serious sequelae, including small bowel obstruction, infertility, chronic pelvic pain, and difficulty in postoperative treatment, including complexity during subsequent surgical procedures. The technology of adhesion prevention has significantly progressed. There are 3 methods approved by the US Food and Drug Administration for the prevention of postoperative adhesions, including Adept((R)), Interceed((R)), and Seprafilm((R)). The latter barrier is the most widely studied. This article reviews the current choices available for adhesion prevention barriers as well as surgical adjuncts that traditionally have been studied for that purpose.


Outcomes of Children and Adolescents Admitted with Diabetic Ketoacidosis at Kenyatta National Hospital (KNH), Kenya.
Diabetic ketoacidosis (DKA) is an acute, major, life-threatening complication that mainly occurs in patients with type 1 diabetes mellitus and is the foremost cause of death in these children. Overall mortality in children with DKA varies from 3.4% to 13.4% in developing countries. There is a need to understand outcomes among children with DKA in sub-Saharan African countries. To determine the death rate and clinical outcomes of children and adolescents aged 0-18 years managed for DKA at Kenyatta National Hospital (KNH). Study Methods. This was a retrospective study carried out among children aged 0-18 years admitted with DKA at KNH between February 2013 and February 2018. The study site was the central records department at KNH. The inclusion criteria were children aged 0-18 years admitted with a diagnosis of DKA based on the ISPAD guidelines biochemical criteria. Out of the 159 files reviewed, the median age of children was 13 years (IQR 10-15). 41.1% of patients had severe DKA while 35.7% had moderate DKA. We reported a mortality of 6.9% while 93.1% of children recovered and were discharged home. The median duration of hospital stay was 8 days. High risk of mortality was reported among children who had high serum creatinine (OR 5.8 (95% CI 1.6-21.2)), decreased urine output (OR 9.0 (95% CI 2.2-37.3)), and altered level of consciousness (OR 5.2 (95% CI 1.1-25.1)). DKA-associated mortality in our study was low at 6.9%. High serum creatinine, decreased urine output, and altered level of consciousness were associated with a significantly higher risk of mortality.


Pharmacogenetics and personalized treatment of type 2 diabetes.
Type 2 diabetes mellitus (T2DM) is a worldwide epidemic with considerable health and economic consequences. T2DM patients are often treated with more than one drug, including oral antidiabetic drugs (OAD) and drugs used to treat diabetic complications, such as dyslipidemia and hypertension. If genetic testing could be employed to predict treatment outcome, appropriate measures could be taken to treat T2DM more efficiently. Here we provide a review of pharmacogenetic studies focused on OAD and a role of common drug-metabolizing enzymes (DME) and drug-transporters (DT) variants in therapy outcomes. For example, genetic variations of several membrane transporters, including SLC2A1/2 and SLC47A1/2 genes, are implicated in the highly variable glycemic response to metformin, a first-line drug used to treat newly diagnosed T2DM. Furthermore, cytochrome P450 (CYP) enzymes are implicated in variation of sulphonylurea and meglitinide metabolism. Additional variants related to drug target and diabetes risk genes have been also linked to interindividual differences in the efficacy and toxicity of OAD. Thus, in addition to promoting safe and cost-effective individualized diabetes treatment, pharmacogenomics has a great potential to complement current efforts to optimize treatment of diabetes and lead towards its effective and personalized care.


In vitro methods for the analysis of motor function in the developing spinal cord of the chick embryo.
The isolated spinal cord of the chick embryo spontaneously generates episodes of motor activity in vitro that can be recorded from muscle nerves and ventral roots. In vitro systems provide stable conditions for intra- and extra-cellular recordings and enable pharmacological and ionic manipulations of the neuronal environment. Studies of motor activity generated by isolated spinal cord have revealed the existence of co-ordinated motor output from early in development, in which antagonist motoneurons alternate in their activity and synergists are co-active. Intra-cellular recordings from single neurons and electronic recordings from muscle nerves have provided insight into the mechanism of flexor and extensor alternation. These studies have revealed that flexor and extensor motoneurons receive a similar de-polarization during each cycle of motor activity, but that the two classes of motoneuron process the de-polarization differently. Flexors fire late in each cycle whereas extensors fire early, which leads to a pattern of alternation. The cellular mechanisms responsible for the differences in the firing behavior of flexor and extensor motoneurons are currently being investigated using techniques that are only possible using the in vitro preparation.


Evaluation of fluorine-18-BPA-fructose for boron neutron capture treatment planning.
Boron neutron capture therapy (BNCT) using 4-[10B]boronophenylalanine-fructose (BPA-Fr) is in Phase II clinical trials to validate BNCT as a treatment for glioblastoma multiforme and melanoma. Successful BNCT depends on knowledge of the distribution of boron-containing agents in both tumor and normal tissue as currently determined by chemical confirmation of boron deposition in surgically removed malignant tissue before BNCT. We used PET to noninvasively obtain in vivo information on the pharmacokinetics of the 18F-labeled analog of BPA-Fr in two patients with glioblastoma multiforme. Time-activity curves generated from the bolus injection of 18F-BPA-Fr were coinvolved to simulate a continuous infusion used for BNCT therapy. Distribution of 18F-BPA-Fr by PET was found to be consistent with tumor as identified by MR imaging. The 18F-BPA-Fr tumor-to-normal brain uptake ratio was 1.9 in Patient 1 and 3.1 in Patient 2 at 52 min after injection. The 18F-BPA-Fr uptake ratio in glioblastoma paralleled that of nonlabeled BPA-Fr seen in patients as previously determined by boron analysis of human glioblastoma tissue obtained from pre-BNCT surgical biopsy. Knowledge of the biodistribution of BPA-Fr enables pre-BNCT calculation of expected tissue dosimetry for a selected dose of BPA-Fr at a specific neutron exposure. Fluorine-18-BPA-Fr PET is capable of providing in vivo BPA-Fr biodistribution data that may prove valuable for patient selection and pre-BNCT treatment planning.


[Biochemical markers of toxic and mutagenic complications of cytostatic pharmacotherapy].
Data are submitted on individual prophylaxis of damage to the genetical apparatus of bodily normal cells in cytostatic therapy of immunodeficiency states by observing changes in biochemical indices, such as activity of enzymes, content of biologically active substances and hormones.


The ReZoom multifocal intraocular lens: 2-year follow-up.
To evaluate distance, intermediate, and near visual acuity and patient satisfaction over a period of 2 years after implantation of the ReZoom multifocal intraocular lens. Fifty-five eyes of 35 cataract patients were included in this retrospective study. Only patients with a preoperative photopic pupillary diameter superior to 3 mm were included. Monocular visual acuities and visual symptoms were compared at different time points. Preoperative mean distance uncorrected visual acuity (UCVA) was 0.5+/-0.3 LogMAR, uncorrected intermediate visual acuity (UCiVA) at 50 cm was 0.6+/-0.3 LogMAR, and near uncorrected visual acuity (UNVA) was J7.8+/-0.6. Mean follow-up was 28.1+/-7.2 months. At 6 months, UCVA improved to 0.05+/-0.09 logMAR (p<0.001), UCiVA to 0.08+/-0.1 LogMAR (p<0.001), and UNVA to J2.4+/-0.4 (p<0.001). At 24 months, UCVA was 0.04+/-0.08 LogMAR, UCiVA was 0.07+/-0.1 LogMAR, and UNVA was J2.3+/-0.7. No significant differences were observed between the values at 6 months versus 24 months. At the 3-month visit, moderate glare and halo were reported by 10% and 13% of patients, respectively. The occurrence of visual symptoms decreased with time, with only 7% and 5% of patients reporting moderate glare and halo at the last visit, respectively. The ReZoom lens provides quality vision at all distances. Between 6 and 24 months of follow-up, a further improvement of optical disturbances rather than uncorrected visual acuity may be expected.


Value of erythrocyte sedimentation rate and serum epo levels in evaluating the condition and prognosis of COPD in the elderly.
To investigate the value of erythrocyte sedimentation rate (ESR) and serum EPO levels in evaluating the condition and prognosis of chronic obstructive pulmonary disease (COPD) in the elderly. 120 elderly patients with acute exacerbation of COPD admitted to our hospital from May 2016 to April 2019 were selected. Pulmonary function tests and CT scans were performed on all patients. According to Gold's guidelines for the diagnosis and treatment of chronic obstructive pulmonary disease, patients with different degrees of illness were divided into mild group, moderate group and severe group. The levels of EPO and ESR were measured in the morning after admission and the differences of EPO and ESR between the three groups were compared. The correlation between EPO, ESR and FEV1% of lung function index was analyzed by linear correlation analysis. There was no significant difference in age, sex, BMI index and course of disease among the three groups (P>0.05); ESR and EPO increased in turn among mild, moderate and severe groups, while FEV1% decreased in turn, with significant differences between the two groups (P<0.05). Negative correlation (r values were - 0.33, - 0.49, P<0.05). ESR and serum EPO levels can reflect the severity of COPD in elderly patients to some extent, and are negatively correlated with FEV1% of lung function indicators, which can provide some clues to the condition and prognosis of COPD in elderly patients.


The quality of citations in major international obstetrics and gynecology journals.
Our goal was to determine the error rate in references in articles published in three major international journals in obstetrics and gynecology. All issues (excluding supplements) for the year 1995 of the American Journal of Obstetrics and Gynecology, the Australian and New Zealand Journal of Obstetrics and Gynaecology, and the British Journal of Obstetrics and Gynaecology were examined. References were numbered sequentially, and 50 randomly selected references from each journal were checked against the original for accuracy. Errors were found in the majority of references. The lowest error rate was 55.6% from the Australian and New Zealand Journal of Obstetrics and Gynaecology, and the highest was 66.7% from the British Journal of Obstetrics and Gynaecology. The difference between journals was not statistically significant. The most frequent types of error were in the title of the article or in the authors' names. Error rates in major international journals in obstetrics and gynecology are high, and care must be taken by authors and journal staff to improve the quality of published articles.


[The significance of leukoaraiosis. A current evaluation and differential diagnosis].
Bilateral symmetric changes in the cerebral hemispheric white matter are found with increasing frequency using CT and MRI techniques. These unspecific changes of the white matter signal are often called leukoaraiosis. They differ from the normal white matter signal. These changes are found with increasing frequency in persons older than 60 years and also patients with dementia and cerebrovascular diseases. The pathogenesis, clinical significance and morphological substrate are unclear. The aim of this review is to summarise the actual knowledge about the etiology and clinical signs and symptoms found in patients with leukoaraiosis. This term should not be used when white matter changes are found in patients younger than 35 years, with an unilateral onset, asymmetric distribution, and extensive changes all over the infra- and supratentorial white matter area. Neuroradiological and clinical criteria are given to differentiate between leukoaraiosis and diseases of the white matter, especially enlarged Virchow-Robin spaces, lacunar infarction, subcortical arteriosclerotic angiopathy (Binswanger's disease), leukoencephalopathy of different origin, and demyelinating diseases.


Principles of moral accounting: How our intuitive moral sense balances rights and wrongs.
We are all saints and sinners: Some of our actions benefit others, while other actions lead to harm. How do people balance moral rights against moral wrongs when evaluating others' actions? Across 9 studies, we contrast the predictions of three conceptions of intuitive morality-outcome-based (utilitarian), act-based (deontologist), and person-based (virtue ethics) approaches. These experiments establish four principles: Partial offsetting (good acts can partly offset bad acts), diminishing sensitivity (the extent of the good act has minimal impact on its offsetting power), temporal asymmetry (good acts are more praiseworthy when they come after harms), and act congruency (good acts are more praiseworthy to the extent they offset a similar harm). These principles are difficult to square with utilitarian or deontological approaches, but sit well within person-based approaches to moral psychology. Inferences about personal character mediated many of these effects (Studies 1-4), explained differences across items and across individuals (Studies 5-6), and could be manipulated to produce downstream consequences on blame (Studies 7-9); however, there was some evidence for more modest roles of utilitarian and deontological processing too. These findings contribute to conversations about moral psychology and person perception, and may have policy and marketing implications.


Pediatric cardiac transplantation using hearts previously refused for quality: a single center experience.
Pediatric donor hearts are regularly refused for donor quality with limited evidence as to which donor parameters are predictive of poor outcomes. We compare outcomes of recipients receiving hearts previously refused by other institutions for quality with the outcomes of recipients of primarily offered hearts. Data for recipients aged ≤18 and their donors were obtained. Specific UNOS refusal codes were used to place recipients into refusal and nonrefusal groups; demographics, morbidity and mortality were compared. Kaplan-Meier analysis with log-rank test was used to determine differences in graft survival. A multivariable Cox proportional hazards model was constructed to determine independent risk factors for postoperative mortality. From July 1, 2000 to April 30, 2011, 182 recipients were transplanted and included for analysis. One hundred thirty received a primarily offered heart; 52 received a refused heart. No difference in postoperative complications or graft survival between the two groups (p = 0.190) was found. Prior refusal was not an independent risk factor for recipient mortality. Analysis of this large pediatric cohort examining outcomes with quality-refused hearts shows that in-hospital morbidity and long-term mortality for recipients of quality-refused hearts are no different than recipients of primarily offered hearts, suggesting that donor hearts previously refused for quality are not necessarily unsuitable for transplant and often show excellent outcomes.


Risk factors for pterygium recurrence after surgical excision with combined conjunctival autograft (CAG) and intraoperative antimetabolite use.
To identify the determinants of recurrence following primary pterygium excision combined with conjunctival autograft (CAG) and intraoperative use of Mitomycin C (MMC) or 5-Fluorouracil (5-FU). A randomized controlled clinical trial comparing 5-FU (50 mg/ml) plus CAG versus MMC (0.01%) plus CAG in preventing recurrence of primary pterygium following excision. A total of 80 eyes of 80 subjects were studied, with 46 eyes in the 5-FU group and 34 eyes in the MMC group. The mean age was 50.7 +/- 13.1 years with a male: female ratio of 0.95:1. Mean follow up period was 35.2 +/- 29.1 weeks. The overall recurrence rate was 10%, with a rate of 8.7% in the 5-FU group and 11.8% in the MMC group. The mean age of the patients who had a recurrence was 38.1 +/- 13.3 years compared to 52.1 +/- 12.4 years in those without a recurrence (p = 0.003). The median size of the pterygium in patients who had a recurrence was 3.2mm, while the median size in patients who did not have a recurrence was 3.0mm (p = 0.8). Five (12.8%) males had a recurrence compared to three (7.3%) females (p = 0.48); while 10.5% of fleshy pterygia recurred compared to none (0%) of the non-fleshy pterygia (p = 1.00). Younger age remains a risk factor for recurrence when both CAG and antimetabolites are combined in the treatment of pterygium, while the effect of gender, size and morphology of the pterygium may be diminished by such combination.


Mortality, life expectancy and causes of death of mildly mentally retarded in Denmark.
Based upon the nationwide Danish registration, all cases with ICD 8 diagnoses 310 and 311 were drawn; 71% lived outside institutions. 7,134 persons were studied for the period 1 January 1976-3 March 1984 and examined in the central register for death, emigration, etc. 5.86%, 446 died during the observation period from 1 January 1976 to 31 March 1984. Mortality tables show estimated survival probability at the end of the 5-year intervals and the life expectancy at the start of the age intervals. Only small differences were found when comparing differences of mortality for sex and residence (institutions or outside institutions). By a linkage study with the Danish Central Register for causes of death in the National Health Service of Denmark, the causes of death were obtained. For males of the age 15-64 an excess mortality of malignant neoplasms, of diseases of the respiratory system, of congenital malformations, and of accidents were found. For females the pattern was less significant.


Monoclonal antibodies against integrin subunits alpha6 and beta1 inhibit migration of gingival epithelium in organ culture.
The main problem in the posterior instrumental treatment of periodontitis is the re-epithelization of the periodontal defects, leading to the formation of an unphysiological, long junctional epithelium inhibiting the regeneration of periodontal attachment. A precondition for the re-epithelization is the interaction between epithelial cells and their extracellular matrix mediated by integrins. Integrins are cellular adhesion molecules (CAM), binding to different structures of the extracellular matrix, e.g., collagen, laminin, or fibronectin. Biopsy specimens of marginal gingiva, composed of epithelium and subepithelial connective tissue, were cultivated on microporous membranes in tissue culture plates. The culture medium was supplemented with monoclonal antibodies directed against human integrin subunits. The period of cultivation was 6 days and the medium was replaced daily. After cultivation, the tissue development was analyzed by histological and immunohistochemical methods. We found that the combination of antibodies directed against the integrin subunits alpha6 and beta1 inhibited the migration of epithelium completely in 9 out of 10 cultures, whereas control cultures containing none or only irrelevant antibodies demonstrated connective tissues completely covered by epithelium. Influencing the regeneration of periodontal tissue on a molecular basis by using antibodies directed against integrin subunits may be of future interest in postsurgical treatment of periodontal diseases.


All-Atom Simulation Method for Zeeman Alignment and Dipolar Assembly of Magnetic Nanoparticles.
Magnetic nanoparticles (MNPs) can organize into novel structures in solutions with excellent order and unique geometries. However, studies of the self-assembly of smaller MNPs are challenging due to a complicated interplay between external magnetic fields and van der Waals, electrostatic, dipolar, steric, and hydrodynamic interactions. Here, we present a novel all-atom molecular dynamics simulation method to enable detailed studies of the dynamics, self-assembly, structure, and properties of MNPs as a function of core sizes and shapes, ligand chemistry, solvent properties, and external field. We demonstrate the use and effectiveness of the model by simulating the self-assembly of oleic acid ligand-functionalized magnetite (Fe3O4) nanoparticles, with spherical and cubic shapes, into rings, lines, chains, and clusters under a uniform external magnetic field. We found that the long-range electrostatic interactions can favor the formation of a chain over a ring, the ligands promote MNP cluster growth, and the solvent can reduce the rotational diffusion of the MNPs. The algorithm has been parallelized to take advantage of multiple processors of a modern computer and can be used as a plugin for the popular simulation software LAMMPS to study the behavior of small MNPs and gain insights into the physics and chemistry of different magnetic assembly processes with atomistic details.


Blood components and OCT reflectivity evaluated in animal model.
To see the relationship between blood components and optical coherence tomography (OCT) reflectivity using an animal model in which the aqueous humor was substituted by different experimental solutions without changing the integrity of the retina. The aqueous humor of an enucleated swine eye was replaced with plasma obtained from healthy volunteers. The OCT reflectivity of the anterior chamber filled with each plasma was calculated from individual OCT images, and was expressed by an arbitrary unit (AU). The concentration of blood components such as cholesterol, hemoglobin (Hb) and bilirubin of each individual was measured, and the correlation between each of them and the OCT reflectivity of aqueous humor in an enucleated swine eye was analyzed. Using the same model, the effects of the single plasma component on OCT reflectivity were examined. Blood samples were obtained from 24 individuals. OCT reflectivity was 30.68 ± 14.8 AU (average ± SD), ranging from 11.11 to 60.31 AU. OCT reflectivity correlated significantly with the concentration of triglycerides (R = 0.634, p = 0.001) and total cholesterol (R = 0.488, p = 0.015) using Spearman's rank correlation coefficient. While a partial correlation analysis showed that it correlated significantly with triglyceride (R = 0.60, p = 0.003), but not total cholesterol. OCT reflectivity was highest in a balanced salt solution (BSS) with Hb (average 42.05 AU), followed by fibrinogen (8.08 AU), bilirubin (6.12 AU) and γ-globulin (2.85 AU). Albumin did not increase the reflectivity of the BSS with a normal concentration (1.11 AU) compared to the control BSS alone (0.73 AU). OCT reflectivity was most strongly affected by the presence of triglycerides among the blood components. Some molecules such as Hb and fibrinogen significantly increase the OCT reflectivity. This information should be helpful for interpreting the OCT findings correctly.


Emotion suppression and acute physiological responses to stress in healthy populations: a quantitative review of experimental and correlational investigations.
Emotion suppression may be linked to poor health outcomes through elevated stress-related physiology. The current meta-analyses investigate the magnitude of the association between suppression and physiological responses to active psychological stress tasks administered in the laboratory. Relevant articles were identified through Medline, PsychINFO, PubMed, and ProQuest. Studies were eligible if they (a) used a sample of healthy, human subjects; (b) assessed physiology during a resting baseline and active psychological stress task; and (c) measured self-report or experimentally manipulated suppression. Twenty-four studies were identified and grouped within two separate random effects meta-analyses based on study methodology, namely, manipulated suppression (k = 12) and/or self-report (k = 14). Experimentally manipulated suppression was associated with greater physiological stress reactivity compared to controls (Hg = 0.20, 95% CI [0.08, 0.33]), primarily driven by cardiac, hemodynamic, and neuroendocrine parameters. Self-report trait suppression was not associated with overall physiological stress reactivity but was associated with greater neuroendocrine reactivity (r = 0.08, 95% CI [0.01, 0.14]). Significant moderator variables were identified (i.e., type/duration of stress task, nature of control instructions, type of physiology, and gender). This review suggests that suppression may exacerbate stress-induced physiological arousal; however, this may differ based upon the chosen methodological assessment of suppression.


Model-based gene selection shows engrailed 1 is associated with antipsychotic response.
Schizophrenia is an highly heritable complex disorder with a significant impact on public health. A variety of antipsychotics are available for treatment of the disorder and individual response to treatment is variable. To date, only a limited number of potential candidate genes have been examined for genetic association with treatment response. As there is lack of understanding of disease etiology and variation in treatment response, a large number of additional genes are potential targets for investigation. A variety of strategies for selecting candidate genes for further investigation are available and in most cases information used is weighed and ranked intuitively by the investigator. We sought to find genes that may influence treatment response in a less biased manner, after integrating heterogeneous data sources related to schizophrenia. A method to select liability and treatment response candidate genes for schizophrenia using multiple data sets was constructed. The method successfully selected DTNBP1, a strong candidate gene for schizophrenia. We then evaluated novel genes picked by the method. Thirty-six single nucleotide polymorphisms in two genes engrailed 1 (EN1) and secretin receptor (SCTR) were genotyped in the Clinical Antipsychotic Trials of Intervention Effectiveness study sample. Outcomes analyzed were the Positive and Negative Syndrome Scale and six different neurocognitive measures. Several of the seven single nucleotide polymorphisms genotyped in the EN1 gene were associated with schizophrenia symptoms (smallest P value=0.0061) and the effects of antipsychotics on symptoms (smallest P value=2.4x10). The estimated probabilities of being a false discovery were 0.14 for symptoms and 0.0012 for drug response. These findings show that EN1 may influence individual variation in response to antipsychotics. In addition, model-based data integration of schizophrenia-related data seems to improve the prior probability of selecting genes that have an effect on antipsychotics response.


Leading Topics in Twitter Discourse on JUUL and Puff Bar Products: Content Analysis.
In response to the recent government restrictions, flavored JUUL products, which are rechargeable closed-system electronic cigarettes (e-cigarettes), are no longer available for sale. However, disposable closed-system products such as the flavored Puff Bar e-cigarette continues to be available. If e-cigarette consumers simply switch between products during the current government restrictions limited to 1 type of product over another, then such restrictions would be less effective. A step forward in this line of research is to understand how the public discusses these products by examining discourse referencing both Puff Bar and JUUL in the same conversation. Twitter data provide ample opportunity to capture such early trends that could be used to help public health researchers stay abreast of the rapidly changing e-cigarette marketplace. The goal of this study was to examine public discourse referencing both Puff Bar and JUUL products in the same conversation on Twitter. We collected data from Twitter's streaming application programming interface between July 16, 2019, and August 29, 2020, which included both "Puff Bar" and "JUUL" (n=2632). We then used an inductive approach to become familiar with the data and generate a codebook to identify common themes. Saturation was determined to be reached with 10 themes. Posts often mentioned flavors, dual use, design features, youth use, health risks, switching 1 product for the other, price, confusion over the differences between products, longevity of the products, and nicotine concentration. On examining the public's conversations about Puff Bar and JUUL products on Twitter, having described themes in posts, this study aimed to help the tobacco control community stay informed about 2 popular e-cigarette products with different device features, which can be potentially substituted for one another. Future health communication campaigns may consider targeting the health consequences of using multiple e-cigarette products or dual use to reduce exposure to high levels of nicotine among younger populations.


A new conceptual understanding of brain function: basic mechanisms of brain-initiated normal and pathological behaviors.
This article attempts to show why classical conceptual views of the brain that can be found in any neuroscience textbook are not capable of providing an adequate explanation of brain-initiated normal and pathological behaviors and why the classical view should therefore be replaced with a new concept of the brain. The major reason for the inadequacy of the classical model is its explanation of the relationship between structure and function in the brain. This article introduces a new brain concept based on two discoveries: the discovery of the neural network computational principle and the discovery of the generic functional organization of hierarchical neural optimal control systems. A neural optimal control system is a learning system that possesses a model of the behavior of its controlled object. A hierarchy of neural optimal control systems is functionally organized in such a way that a higher level neural optimal control system treats a lower one as its controlled object and creates a model of its behavior. The ability of the new conceptual brain model to explain brain mechanisms of normal and pathological behaviors is demonstrated through the examples of spinal reflexes and central pattern generators, the cerebellum, skeletomotor cortico-basal ganglia-thalamocortical loop, and Parkinson's disease and some other brain disorders. In this article, a new understanding of the relationship between structure and function in the brain is introduced. This article also discusses organizational and educational changes in the neurosciences that may be necessary to accelerate a broad acceptance of this new concept of the brain.


Rapid Detection of Brucella spp. and Elimination of Carryover Using Multiple Cross Displacement Amplification Coupled With Nanoparticles-Based Lateral Flow Biosensor.
Brucella spp.is capable of causing disease in a range of animal hosts, and human brucellosis is regarded as a life-threating disease. A novel isothermal amplification technique, termed multiple cross displacement amplification (MCDA), was employed for detecting all Brucella species strains. Brucella-MCDA targets the Bscp31 gene (Brucella species-specific gene) to specifically design a set of 10 primers. The Brucella-MCDA can be coupled with nanoparticles-based lateral flow biosensor (LFB) for highly specific, simple, rapid, and visual detection of Brucella-specific amplicons. Using the protocol, a MCDA amplification followed by 2 min LFB resulted in visualization of DNA products trapped at the LFB test line. Various species of Gram-positive and Gram-negative strains are applied for optimizing and evaluating the target assay. Optimal MCDA condition is found to be 63°C for 40 min, with detection limits at 10 fg of templates in the pure cultures. The specificity of MCDA-LFB technique is of 100%, and no cross-reactions to non-Brucella strains are observed according to the specificity examination. Furthermore, dUTP and AUDG enzyme are added into the MCDA reaction mixtures, which are used for removing false-positive amplification generating from carryover contamination. Thus, 20 min for rapid template extraction followed by AUDG digestion (5 min), MCDA (40 min) combined with LFB detection (2 min) resulted in a total assay time of ~70 min. In sum, Brucella-MCDA-LFB technique is a rapid, simple, reliable, and sensitive method to detect all Brucella species strains, and can be used as potential screening tool for Brucella strains in various laboratories.


Anterior Ischemic Optic Neuropathy as a Manifestation of HELLP Syndrome.
Thrombotic microangiopathies (TMAs) are a group of disorders characterized by occurrence of thrombi of fibrin and/or platelets with microvascular occlusion and organ ischemia especially the kidney and brain. Hemolysis with a microangiopathic blood smear, elevated liver enzymes, and low platelet count (HELLP syndrome) is a type of TMA peculiar to pregnancy and may be associated with neurological complications. Visual complications in HELLP are usually related to cortical blindness. We present the first case of HELLP associated with bilateral anterior ischemic optic neuropathy (AION) and blindness which resolved with plasma exchange.


Relationship of Radiographic and Clinical Parameters With Hallux Valgus and Second Ray Pathology.
Hallux valgus is frequently associated with additional forefoot pathologies, including hammertoes and midfoot osteoarthritis (OA). However, the pathogenesis of these concurrent pathologies remains to be elucidated. We sought to determine whether there is a relationship between demographic and radiographic parameters and the incidence of secondary pathologies in the setting of a bunion, with an emphasis on second tarsometatarsal (TMT) OA and hammertoes. A total of 153 patients (172 feet) who underwent reconstruction for hallux valgus were divided into 3 groups: (1) bunion only (61 patients), (2) bunion with hammertoe without second TMT joint OA (78 patients), and (3) bunion with second TMT joint OA (14 patients). Preoperative age, sex, and body mass index (BMI) as well as hallux valgus angle (HVA), intermetatarsal angle (IMA), metatarsus adductus angle (MAA), ratio of second to first metatarsal length, and Meary's angle were recorded. One-way analysis of variance (normality demonstrated) and Kruskal-Wallis (normality not demonstrated) tests were used to assess differences in continuous variables. Post hoc tests were conducted with the Bonferroni technique. Associations between discrete variables and the study groups were analyzed using χ2 tests. Following the univariate analysis, multinomial logistic regression models were built to determine potential risk factors for hammertoe or TMT OA group placement. Patients in the hammertoe and TMT OA groups were significantly older than patients in the bunion only group ( P < .001 for both pairwise comparisons) and had significantly higher BMIs ( P = .024 and P < .001, respectively). Patients in the TMT OA group had a significantly higher mean HVA than patients in the bunion-only group ( P = .004) and a significantly higher mean MAA relative to both other study groups ( P ≤ .001 for both comparisons). IMA, Meary's angle, and the ratio of second to first metatarsal length did not differ significantly between groups. In the multivariate analysis, hammertoe group assignment was predicted only by age and HVA, while midfoot OA group assignment was predicted by age, HVA, BMI, and MAA. Our data show that older age and increased HVA were predictors of both second ray pathologies studied. Higher BMI and MAA were predictive only of TMT joint OA. These data may help identify patients with hallux valgus who are at greater risk for developing secondary pathologies. Level III, retrospective comparative series.


[Analysis on primate lentivirus genome dimerization in virion].
The genomic RNA of retrovirus, including the primate lentivirus such as HIV, always form dimers in matured virions. It is likely that the presence of two genomes in one virion is advantageous for survival, providing an extra template that can be used when one RNA molecule is damaged, and/or giving genetic variety to their progeny. However, these ideas might not fully explain why the virion have to carry multiple identical RNAs in spite of the severe limitation of the space. We developed and utilized a novel system to investigate viral RNA dimerization in virion clearly and simply without affecting RNA packaging. The results of precise mapping of dimerization functional region strongly suggested that the RNA dimerization is one of the essential steps of RNA packaging.


[Effects of millimeter wave irradiation with different frequency and power density on their offsprings in mice].
To determine the threshold of millimeter wave irradiation leading to fetal damage in mice and to clarify the mechanism of decrease in their learning and memory function. Pregnant mice were irradiated by millimeter wave with frequencies of 37.4, 42.2, 53.0 and 60.0 GHz at power densities of 1 to 8 mW/cm2 for two hours daily from the 6th to 15th day of their gestation. Learning and memory functions of their offsprings were tested by a Y-type electric maze. M-cholinergic receptor (M-R), monoamine transmitter and arginine vasopressor (AVP) in the brain were determined for their offsprings by receptor radiation binding analysis (RBA), high performance liquid chromatography-electrochemical detection (HPLC-ECD) and radioimmunoassay (RIA). The minimal power density of millimeter wave of 37.4, 42.2, and 53.0, 60.0 GHz causing the decrease in learning and memory function, increase of Bmax in the hippocampus and decrease in dopamine (DA) in the brain of the adult offspring mice was five and three mW/cm2 and that causing the decrease in AVP in the hypothalamus was eight and five mW/cm2. Severity of damage in fetal offspring mice caused by irradiation increased with the power density of millimeter wave. Millimeter wave could not cause the increase of their body temperature in pregnant mice. Threshold of millimeter wave with frequencies of 37.4, 42.2 and 53.0, 60.0 GHz causing fetal damage in mice was three to five mW/cm2 and one to three mW/cm2, respectively. The decrease in learning and memory functions in offspring mice related with lowering of AVP and DA in the brain and of activity in cholinergic nerve. All these were caused by the non-thermal effects of millimeter wave without a frequency-specific pattern.


[Histological changes in the ligamentum flavum in patients with spinal stenosis].
In 21 patients with spinal stenosis the ligamentum flavum was removed, histologically processed and the calcification was measured with an image analyzing computer. Nearly all the ligaments were calcified: on average 0.17%, with a maximum of 3.8%. There was a significant correlation between age and calcification. We compared these findings with those of a group of "normals". There we only found minimal calcification in 3 of 20 segments (0.025%, 0.049%, 0.22%). As these people were on average 85 years of age, this can be looked upon as normal degenerative changes. This illustrates the important role of calcification of the ligamentum flavum for spinal stenosis.


The San1 Ubiquitin Ligase Avidly Recognizes Misfolded Proteins through Multiple Substrate Binding Sites.
Cellular homeostasis depends on robust protein quality control (PQC) pathways that discern misfolded proteins from functional ones in the cell. One major branch of PQC involves the controlled degradation of misfolded proteins by the ubiquitin-proteasome system. Here ubiquitin ligases must recognize and bind to misfolded proteins with sufficient energy to form a complex and with an adequate half-life to achieve poly-ubiquitin chain formation, the signal for protein degradation, prior to its dissociation from the ligase. It is not well understood how PQC ubiquitin ligases accomplish these tasks. Employing a fully reconstituted enzyme and substrate system to perform quantitative biochemical experiments, we demonstrate that the yeast PQC ubiquitin ligase San1 contains multiple substrate binding sites along its polypeptide chain that appear to display specificity for unique misfolded proteins. The results are consistent with a model where these substrate binding sites enable San1 to bind to misfolded substrates avidly, resulting in high affinity ubiquitin ligase-substrate complexes.