Cephradine in urinary tract infections: a double-blind comparison with ampicillin.
A double-blind trial was carried out comparing cephradine and ampicillin in the treatment of urinary tract infections in 42 females attending a hospital Department of Obstetrics and Gynaecology. Results showed that patients did better in the cephradine group than the ampicillin group, both bacteriologically and clinically. The numbers in each group were small, however, and did not reach statistical significance.


Refeeding syndrome in adults with celiac crisis: a case report.
Refeeding syndrome is a rare and life-threatening pathology with polyvisceral manifestations occurring in severely malnourished patients. It is rarely described in adults with celiac disease. We report the case of a 28-year-old Tunisian woman followed up for celiac disease, who did not adhere to the gluten-free diet. She presented to our hospital with celiac crisis manifested by severe diarrhea, and metabolic and electrolyte disturbances. The treatment of electrolyte abnormalities, hydration, and nutritional support was marked by the occurrence on the fifth day of refeeding syndrome with psychomotor agitation followed by respiratory distress and a state of cardiogenic shock. Refeeding syndrome is still under-recognized. It should be systematically prevented for high-risk patients. Nutritional support in patients with celiac crisis should be monitored carefully since the risk of refeeding syndrome is very high with a poor prognosis.


Redlining and Lead Poisoning: Causes and Consequences.
In 1934, the Federal Housing Authority precluded mortgage loans to residents of neighborhoods with non-White families or where housing was deteriorated; these were declared "hazardous" and labeled red on maps. In 1962 three redlined north Brooklyn neighborhoods had 41 children, all Black and Puerto Rican, with lead levels >60ug/dL. A review of public polices in the U.S. from 1898 to the present revealed that lead poisoning followed an income gradient with multiple disproportionate effects on non-White children in redlined neighborhoods. The poisonings diminished when federal and local regulations prevented lead exposure. While redlining had profound influences on both likelihood and severity of lead poisoning and its consequences, it was a mediator of effects. The principal causes were federal policies failing to prevent environmental contamination and local governments failing to prevent exposure.


A simple procedure for elimination of fungal contamination for enumeration of iron-oxidizing bacteria from bioleaching matrix of sewage sludge.
Enumeration of iron-oxidizing bacteria from the bioleaching matrix of sewage sludge is always confronted by fungal contamination. The objective of the present study was to find a reliable and simple method to remove fungal growth and to shorten the incubation time for facilitating enumeration of the iron-oxidizers from complex sludge samples. The results demonstrated that filtering the sludge sample through sterile No. 5 Whatman filter paper before serial dilution was effective in eliminating the fungal growth on agarose media. Both the counts and the incubation time required for enumeration were highly dependent on the medium pH, with maximum counts at pH 2.5-2.75. Medium prepared at pH values outside of this range led to lower counts and a longer lag time for colony formation. However, the introduction of heterotrophic microorganisms into the solid medium did not show further improvement in enumeration efficiency and shortening of the incubation period. By incorporating the optimal conditions obtained, the incubation time could be reduced to 7 and 10 d for pure cultures and sludge samples, respectively.


Shrimps that pay attention: saccadic eye movements in stomatopod crustaceans.
Discovering that a shrimp can flick its eyes over to a fish and follow up by tracking it or flicking back to observe something else implies a 'primate-like' awareness of the immediate environment that we do not normally associate with crustaceans. For several reasons, stomatopods (mantis shrimp) do not fit the general mould of their subphylum, and here we add saccadic, acquisitional eye movements to their repertoire of unusual visual capabilities. Optically, their apposition compound eyes contain an area of heightened acuity, in some ways similar to the fovea of vertebrate eyes. Using rapid eye movements of up to several hundred degrees per second, objects of interest are placed under the scrutiny of this area. While other arthropod species, including insects and spiders, are known to possess and use acute zones in similar saccadic gaze relocations, stomatopods are the only crustacean known with such abilities. Differences among species exist, generally reflecting both the eye size and lifestyle of the animal, with the larger-eyed more sedentary species producing slower saccades than the smaller-eyed, more active species. Possessing the ability to rapidly look at and assess objects is ecologically important for mantis shrimps, as their lifestyle is, by any standards, fast, furious and deadly.


Visual function and patient experience after bilateral implantation of toric intraocular lenses.
To evaluate the efficacy, stability, predictability, and patient-reported outcomes of bilateral toric intraocular lens (IOL) implantation in cases of cataract with preexisting astigmatism. Fourteen universities, hospitals, or private practices, Canada. Patients with cataracts and corneal astigmatism from 1.00 to 2.50 diopters (D) were included in a prospective study of bilateral AcrySof toric IOL implantation. Binocular uncorrected distance visual acuity (UDVA), manifest refraction, and IOL rotational stability were assessed 1 day and 1, 3, and 6 months postoperatively. Patients completed a questionnaire that assessed spectacle independence, visual disturbances, and satisfaction with vision (1 = completely unsatisfied; 10 = completely satisfied) preoperatively and 3 and 6 months postoperatively. The study included 117 patients (234 eyes). The binocular UDVA was 20/40 or better in 99% of patients and 20/20 or better in 63% of patients. The mean residual refractive astigmatism was 0.4 D +/- 0.4 (SD). The spherical equivalent was within +/-0.5 D of target in 77% of eyes. At last observation, IOL alignment was within +/-5 degrees in 91% of eyes and within +/-10 degrees in 99%. Sixty-nine percent of patients reported never using distance spectacles. The frequency and severity of halos and glare were significantly reduced from preoperatively to postoperatively. Satisfaction with vision was rated 7 or higher by 94% of patients. Bilateral implantation of toric IOLs yielded excellent and stable visual outcomes that patients rated as highly satisfactory. No author has a financial or proprietary interest in any material or method mentioned. Additional disclosures are found in the footnotes.


Mothers' and fathers' changing perceptions of their male and female infants over the course of pregnancy.
Twelve pregnant women and their spouses who had undergone ultrasonography and knew their child's gender were compared with 12 pregnant women and their spouses who had undergone ultrasonography but did not know their child's gender. Parents were interviewed (a) prior to receiving the ultrasound, (b) immediately after the ultrasound, and (c) following their infant's birth. Using the adjectives rating scales, and replicating the procedures developed by Rubin, Provenzano, and Luria (1974), parents' perceptions of their infants were measured. ANOVA results indicated that parents viewed their infants to be softer, finer, littler, cuddlier, easier, calmer, more inactive, more beautiful, more awkward, quieter, weaker, and somewhat more delicate following birth than during the preceding measurement period(s). Mothers viewed their infants to be softer, more nervous, more fussy, more excitable, and more noisy than did fathers. Supporting Rubin et al.'s (1974) findings, several differences emerged between parents' perceptions of boys and girls, particularly by the time the infants were born. Following birth, parents perceived girls to be finer, smaller, less coordinated, quieter, weaker, and more delicate than boys. No differences were found as a result of parents being informed of their infants' gender prior to birth.


Surface completion affected by luminance contrast polarity and common motion.
Our visual system ably integrates the visible parts of a partially occluded surface with the occluded parts (amodal surface completion), mainly by relying on the surface boundary contours of the image. Less known, is whether the visual system also utilizes surface feature information, such as luminance contrast polarity, for surface completion. We conducted three experiments to investigate this issue. Experiment 1 found that when visible segments of a partially occluded rectangle with the same luminance contrast polarity move behind an occluding surface, observers perceive the visible segments as part of the occluded rectangle moving cohesively behind the occluding surface. However, when the visible segments have opposite luminance contrast polarity, the global motion of the segments is barely perceived, suggesting a failure of amodal surface integration. Experiment 2 revealed that this same luminance contrast polarity constraint applies to amodal surface integration of a display without an explicit occluding surface image. Experiment 3 showed that both the shape and luminance contrast polarity of the visible segments of the partially occluded rectangle affect amodal surface completion. Together, these findings demonstrate that luminance contrast polarity, along with surface boundary contour, are important cues for amodal surface integration.


In addition to SEC11, a newly identified gene, SPC3, is essential for signal peptidase activity in the yeast endoplasmic reticulum.
Among the three characterized subunits comprising the signal peptidase complex of the yeast Saccharomyces cerevisiae (Sec11p, Spc1p, and Spc2p), only Sec11p is essential for cell growth, signal peptide cleavage, and signal peptidase-dependent protein degradation. Here we report the cloning of the SPC3 gene encoding the homolog to mammalian signal peptidase subunit SPC22/23. We find that Spc3p is also required for cell growth and signal peptidase activity within the yeast endoplasmic reticulum.


Microarchitectures of Barrett's esophagus associated with DNA methylation status.
Aim: DNA methylation is involved in esophageal adenocarcinoma (EAC) and Barrett's esophagus (BE). Microarchitectures of on-neoplastic BE associated with DNA methylation status were examined using magnifying narrow-band imaging (NBI) endoscopy. Patients and methods: Using biopsies from non-neoplastic BE without cancer (n = 66; N group), with EAC (n = 27; ADJ group) and EAC tissue (n = 22; T group), methylation of N33, DPYS, SLC16A12, miR124a3 and miR34bc genes were quantified. Magnifying NBI features of non-neoplastic BE were classified according to their morphologies. Results: The ADJ and T groups presented higher DNA methylation compared with the N group. Magnifying NBI endoscopic features of non-neoplastic BE also correlated with DNA methylation as an independent factor. Conclusion: Microarchitectures of BE visualized by magnifying NBI endoscopy correlated with DNA methylation.


Natural selection and neutral evolution jointly drive population divergence between alpine and lowland ecotypes of the allopolyploid plant Anemone multifida (Ranunculaceae).
Population differentiation can be driven in large part by natural selection, but selectively neutral evolution can play a prominent role in shaping patters of population divergence. The decomposition of the evolutionary history of populations into the relative effects of natural selection and selectively neutral evolution enables an understanding of the causes of population divergence and adaptation. In this study, we examined heterogeneous genomic divergence between alpine and lowland ecotypes of the allopolyploid plant, Anemone multifida. Using peak height and dominant AFLP data, we quantified population differentiation at non-outlier (neutral) and outlier loci to determine the potential contribution of natural selection and selectively neutral evolution to population divergence. We found 13 candidate loci, corresponding to 2.7% of loci, with signatures of divergent natural selection between alpine and lowland populations and between alpine populations (Fst = 0.074-0.445 at outlier loci), but neutral population differentiation was also evident between alpine populations (FST = 0.041-0.095 at neutral loci). By examining population structure at both neutral and outlier loci, we determined that the combined effects of selection and neutral evolution are associated with the divergence of alpine populations, which may be linked to extreme abiotic conditions and isolation between alpine sites. The presence of outlier levels of genetic variation in structured populations underscores the importance of separately analyzing neutral and outlier loci to infer the relative role of divergent natural selection and neutral evolution in population divergence.


Health literacy: universal precautions needed.
Inadequate health literacy adversely affects health care outcomes and the quality of life of 90 million Americans and costs the health care system dollars 73 billion annually. Current strategies addressing inadequate health literacy primarily target physicians, nurses, and pharmacists but omit the allied health practitioners responsible for providing most patient services. The 2003 Coalition for Allied Health Leadership Health Literacy Project team undertook a survey of allied health professionals and educators to assess their awareness and needs concerning inadequate health literacy. Less than one third of all respondents were aware of the issues surrounding health literacy or that health literacy resources are available or had institutional policy or goals to address health literacy. Brochures and videos were identified most frequently as new resources needed to establish or increase the effectiveness of health literacy awareness programs. The results of this project indicated that there is substantial opportunity to increase awareness of the impact of health literacy, to develop and assess institutional policies toward health literacy, and to create new resources to promote health literacy within the allied health professions. Any approach to improving health literacy must be universal by involving all health care professionals and all patients in the intervention.


Bacterial TANGO2 homologs are heme-trafficking proteins that facilitate biosynthesis of cytochromes c.
Heme, an essential molecule for virtually all living organisms, acts primarily as a cofactor in a large number of proteins. However, how heme is mobilized from the site of synthesis to the locations where hemoproteins are assembled remains largely unknown in cells, especially bacterial ones. In this study, with Shewanella oneidensis as the model, we identified HtpA (SO0126) as a heme-trafficking protein and homolog of TANGO2 proteins found in eukaryotes. We showed that HtpA homologs are widely distributed in all domains of living organisms and have undergone parallel evolution. In its absence, the cytochrome (cyt) c content and catalase activity decreased significantly. We further showed that both HtpA and representative TANGO2 proteins bind heme with 1:1 stoichiometry and a relatively low dissociation constant. Protein interaction analyses substantiated that HtpA directly interacts with the cytochrome c maturation system. Our findings shed light on cross-membrane transport of heme in bacteria and extend the understanding of TANGO2 proteins. IMPORTANCE The intracellular trafficking of heme, an essential cofactor for hemoproteins, remains underexplored even in eukaryotes, let alone bacteria. Here we developed a high-throughput method by which HtpA, a homolog of eukaryotic TANGO2 proteins, was identified to be a heme-binding protein that enhances cytochrome c biosynthesis and catalase activity in Shewanella oneidensis. HtpA interacts with the cytochrome c biosynthesis system directly, supporting that this protein, like TANGO2, functions in intracellular heme trafficking. HtpA homologs are widely distributed, but a large majority of them were found to be non-exchangeable, likely a result of parallel evolution. By substantiating the heme-trafficking nature of HtpA and its eukaryotic homologs, our findings provide general insight into the heme-trafficking process and highlight the functional conservation along evolution in all living organisms.


Design of programmable post-translational switch control platform for on-demand protein secretion in mammalian cells.
The development of novel strategies to program cellular behaviors is a central goal in synthetic biology, and post-translational control mediated by engineered protein circuits is a particularly attractive approach to achieve rapid protein secretion on demand. We have developed a programmable protease-mediated post-translational switch (POSH) control platform composed of a chimeric protein unit that consists of a protein of interest fused via a transmembrane domain to a cleavable ER-retention signal, together with two cytosolic inducer-sensitive split protease components. The protease components combine in the presence of the specific inducer to generate active protease, which cleaves the ER-retention signal, releasing the transmembrane-domain-linked protein for trafficking to the trans-Golgi region. A furin site placed downstream of the protein ensures cleavage and subsequent secretion of the desired protein. We show that stimuli ranging from plant-derived, clinically compatible chemicals to remotely controllable inducers such as light and electrostimulation can program protein secretion in various POSH-engineered designer mammalian cells. As proof-of-concept, an all-in-one POSH control plasmid encoding insulin and abscisic acid-activatable split protease units was hydrodynamically transfected into the liver of type-1 diabetic mice. Induction with abscisic acid attenuated glycemic excursions in glucose-tolerance tests. Increased blood levels of insulin were maintained for 12 days.


Synthesis of tris(quinoline)monochloroplatinum(II) Chloride and its Activity Alone and in Combination with Capsaicin and Curcumin in Human Ovarian Cancer Cell Lines.
Currently used platinum drugs fail to provide long-term cure for ovarian cancer mainly because of acquired drug resistance. With the idea that the difference may translate into an altered spectrum of activity, monofunctional planaramineplatinum(II) complex tris(quinoline)monochloro-platinum chloride (coded as LH5) was synthesized and investigated for its activity against human ovarian A2780, cisplatin-resistant A2780 (A2780(cisR)) and ZD0473-resistnat A2780 (A2780(ZD0473R)) cancer cell lines alone and in combination with the phytochemicals capsaicin (Caps) and curcumin (Cur) as a function of concentration and sequence of administration. Cell viability was quantified using the MTT reduction assay, while combination was used as a quantitative measure of the combined drug action. LH5 is found to be more active than cisplatin (CS) against both resistant cell lines. Combination of LH5 with capsaicin showed synergism in all three cell lines, with the bolus being most synergistic. Lack of association between the levels of platinum accumulation and platinum-DNA with cytotoxicity can be seen to indicate that binding with DNA may not be the main determinant of activity of LH5. Greater activity of LH5 compared to cisplatin, especially against the resistant cell lines, indicates that the compound may have the potential for development as a novel anticancer drug and that its combination with phytochemicals can serve to further enhance drug efficacy.


Locally advanced rectal cancer: the importance of a multidisciplinary approach.
Rectal cancer accounts for a relevant part of colorectal cancer cases, with a mortality of 4-10/100000 per year. The development of locoregional recurrences and the occurrence of distant metastases both influences the prognosis of these patients. In the last two decades, new multimodality strategies have improved the prognosis of locally advanced rectal cancer with a significant reduction of local relapse and an increase in terms of overall survival. Radical surgery still remains the principal curative treatment and the introduction of total mesorectal excision has significantly achieved a reduction in terms of local recurrence rates. The employment of neoadjuvant treatment, delivered before surgery, also achieved an improved local control and an increased sphincter preservation rate in low-lying tumors, with an acceptable acute and late toxicity. This review describes the multidisciplinary management of rectal cancer, focusing on the effectiveness of neoadjuvant chemoradiotherapy and of post-operative adjuvant chemotherapy both in the standard combined modality treatment programs and in the ongoing research to improve these regimens.


Arp2/3 complex is essential for actin network treadmilling as well as for targeting of capping protein and cofilin.
Lamellipodia are sheet-like protrusions formed during migration or phagocytosis and comprise a network of actin filaments. Filament formation in this network is initiated by nucleation/branching through the actin-related protein 2/3 (Arp2/3) complex downstream of its activator, suppressor of cAMP receptor/WASP-family verprolin homologous (Scar/WAVE), but the relative relevance of Arp2/3-mediated branching versus actin filament elongation is unknown. Here we use instantaneous interference with Arp2/3 complex function in live fibroblasts with established lamellipodia. This allows direct examination of both the fate of elongating filaments upon instantaneous suppression of Arp2/3 complex activity and the consequences of this treatment on the dynamics of other lamellipodial regulators. We show that Arp2/3 complex is an essential organizer of treadmilling actin filament arrays but has little effect on the net rate of actin filament turnover at the cell periphery. In addition, Arp2/3 complex serves as key upstream factor for the recruitment of modulators of lamellipodia formation such as capping protein or cofilin. Arp2/3 complex is thus decisive for filament organization and geometry within the network not only by generating branches and novel filament ends, but also by directing capping or severing activities to the lamellipodium. Arp2/3 complex is also crucial to lamellipodia-based migration of keratocytes.


Distribution characteristics of pathogens in different stages of pressure ulcers and the therapeutic effect of linear polarized polychromatic light combined with silver sulfadiazine cream.
To investigate the distribution characteristics of pathogens in different stages of pressure ulcers and observe the application of linear polarized polychromatic light (LPPL) combined with silver sulfadiazine cream in treating varying stages of pressure ulcers. This study comprised 88 patients with pressure ulcers who were enrolled in the department of burn and plastic surgery of our hospital from April 2019 to April 2022. The wound exudates from patients were collected, followed by analyzing the distribution of pathogens in different stages of pressure ulcers. Patients were randomly divided into 2 groups. The first group (n = 44) received LPPL combined with silver sulfadiazine. The other group was intervened with LPPL group only for 2 weeks. The clinical efficacy, condition, and pain in the 2 groups, as well as the healing timeframes for patients were measured at different stages. The findings showed that among 88 patients with pressure ulcers, 62 were infected, and the infection rate was 70.45%. The pathogens that were observed in stage II and III to IV pressure ulcers were mainly Gram-negative bacteria. The total effective rate in the combined group was 90.91%, which was much higher than that of LPPL group (70.45%). Compared with LPPL group, the pressure ulcer scale for healing and visual analogue scale scores in the combined group were markedly lower (P < .05). It is important to note that in LPPL group, the healing time of patients in stage II and stage III to IV in the combined arm were 9.76 ± 2.38 days and 13.19 ± 2.54 days, respectively. The corresponding time in the LPPL group was prolonged to 13.20 ± 3.76 and 18.82 ± 4.17 days, respectively. The main pathogens associated with wound infection in patients with pressure ulcers are Gram-negative bacteria. The curative effects of LPPL combined with sulfadiazine silver cream on patients with pressure ulcer is obviously improved, and the recovery and pain relief are faster while the healing time of pressure ulcer is shorter.


Altered Cervical Vestibular-Evoked Myogenic Potential in Children with Attention Deficit and Hyperactivity Disorder.
Emerging evidence suggests that children with attention deficit and hyperactivity disorder (ADHD) present more difficulties in standing and walking balance than typically developing children. Most of previous studies have assessed these functions using postural and sensory organization tests showing differences in balance performance between control and ADHD children. However, to date, it is unknown whether these balance alterations are accompanied with vestibular dysfunction. The principal aim of this study is to evaluate vestibular otolith function in ADHD and matched control children. We assessed vestibular otolith function in children with ADHD and controls using the subjective visual vertical (SVV) bucket test and cervical vestibular-evoked myogenic potentials (cVEMPs). In addition, gait and balance were evaluated using the dynamic gait index (DGI) and computerized posturography. Non-significant differences between groups were obtained in SVV evaluation. DGI results show lower scores for overall test performance in children with ADHD (p < 0.001), while computerized postural recordings showed significant differences for the limit of stability between groups (p = 0.02). cVEMPs in response to 500 Hz tone bursts presented at 100 dB were absent or reduced in children with ADHD, as revealed by differences in P1 and N1 peak-to-peak amplitudes between groups (p < 0.01). These findings suggest that vestibular brainstem reflexes are altered in a subset of children with ADHD. We propose to include cVEMP reflexes in the clinical evaluation of ADHD patients.


[Evaluation of a one step sandwich enzymeimmunoassay for serum erythropoietin--serum erythropoietin values in polycythemia vera and related hematological disorders].
We evaluated a newly developed enzymeimmunoassay for serum erythropoietin (Epo) and investigated relationship between Epo levels and hematological disorders. This method has several advantages including simplicity, high sensitivity, good precision. Moreover, the procedure requires only about 2.5 hours. Samples from 134 healthy subjects showed a normal logarithmic distribution, and its normal range was 4.5 approximately 21.3 mU/ml. The levels of Epo in normal subjects and various hematological disorders were as follows: 10.5 +/- 4.1 (mean +/- SD mU/ml) in normal subjects, 2.2 +/- 1.7 in polycythemia vera (PV), 6.1 +/- 3.1 in essential thrombocythemia, 17.8 +/- 27.3 in chronic myelogeneous leukemia, 3.6 +/- 1.8 in stress erythrocytosis, 39.4 and 14.1 in two cases of primary myelofibrosis, 1289 +/- 4798 in iron deficiency anemia and 6564 +/- 10870 in aplastic anemia. In patients with PV, serum Epo were low and did not correlate with hemoglobin concentration. However, inverse correlation was found between changes of Epo levels and hemoglobin levels in most patients. In cases in which PV progressed into myelofibrosis, anemia developed and Epo levels increased accordingly. These results suggest that the method is thought to be useful and reliable for the diagnosis and monitoring of PV and related hematological disorders.


Usefulness of a Telemedicine Program in Refractory Older Congestive Heart Failure Patients.
Home telemonitoring is a modern and effective disease management model that is able to improve medical care, quality of life, and prognosis of chronically ill patients, and to reduce expenditure. The objective of this study was to evaluate the efficacy, costs, and patients' and caregivers' acceptance of our model of telemedicine in a high-risk chronic heart failure (CHF) older population. Patients with high risk/refractory CHF were included. In the case of alarm parameters' modifications, a cardiologist decided to inform the emergency department (ED), the patient's General Practioner, or to programme a clinical ambulatory control. Forty-eight CHF patients (28 males; 58.3%), with a mean age of 80.4 ± 7.7 years, entered this clinical experience. During the 20-months follow-up, four patients dropped out from counselling (8.3%), ambulatory clinical control within-24 h was planned in 18% of patients, 11% of patients were admitted to an ED, and 18% were hospitalized. Thirteen patients (29.5%) died a cardiac death; hospital admissions for heart failure decreased during the year after the enrolment when compared to the year before (from 35 to 12 acute HF hospitalizations/year; p = 0.0001). Moreover, in these HF patients followed, accesses to an ED for an acute episode of HF decompensation reduced from 21/year to five/year (p = 0.0001). The economic expenditure, calculated for the year before and after the enrolment, reduced from 116.856 Euros to 40.065 Euros/year. A telemedicine surveillance in high-risk older CHF patients determines a continuous and active contact between patients/caregivers, the Heart Failure Clinic, and family physicians, permitting an early evaluation of signs and symptoms of acute decompensation.


Changes in glutathione peroxidase and tissue selenium concentrations of broilers after consuming a diet adequate in selenium.
Three experiments (EXP) were conducted with commercial broilers to develop a low-Se diet for comparing plasma glutathione peroxidase (pGPX3) concentrations and then to compare pGPX3 and plasma and tissue Se concentrations in broilers fed this low-Se diet after being supplemented with sodium selenite (SS) or Se-enriched yeast (SY). With the exception of Se, all diets were nutritionally adequate. The EXP lasted from 0 to 20 or 22 d posthatching, and treatments were replicated with 6 to 8 pens of 6 to 15 chicks per pen. The results of EXP 1 and 2 indicated that a cornstarch-dextrose diet containing 10% torula yeast and 31% soybean meal (SBM) resulted in similar gain as a corn-SBM (C-SBM) diet, but the cornstarch-dextrose-torula yeast-SBM diet with no added Se reduced pGPX3 activity 6-fold. In EXP 3, the treatments were a C-SBM diet with 0 or 0.30 ppm added Se from SS or SY. These diets were fed from 0 to 10 d posthatching. Beginning on d 10, all broilers were fed the cornstarch-dextrose-torula yeast-SBM, low-Se diet. On d 10, 13, 16, 19, and 22, three broilers per replicate were randomly selected for plasma and tissue collection. Treatment differences were significant at P < 0.05. Daily gain, daily feed intake, and gain:feed were not affected by diet during the 0-to-10-d or 0-to-22-d periods. Plasma GPX3 activity and plasma, liver, and breast Se concentrations were greater in broilers previously fed the diets with added Se, regardless of source, than in those fed the C-SBM diet, except for liver Se concentration on d 19 of broilers previously fed the SS diet. The pGPX3 concentrations were not different in broilers previously fed either Se diet on d 10 and 13 but were greater in broilers previously fed the SY diet on d 16, 19, and 22. Plasma Se concentrations were not different in broilers previously fed diets with SS or SY on d 10 and 22 but were greater in broilers previously fed the SY diet on d 13, 16, and 19. Breast Se concentrations were greater in broilers previously fed the SY diet than in those fed the SS diet on each day. Liver Se concentrations were not different in broilers previously fed SS or SY diets on d 19 and 22 but were greater in those previously fed the SY diet on d 10, 13, and 16. These results indicated that SY supplementation in broiler diets resulted in greater tissue Se concentrations than SS and that pGPX3 and tissue Se concentrations remained greater in birds previously fed a diet with SY than in those fed SS after being fed a low-Se diet.


Pulmonary nocardiosis with bloodstream infection diagnosed by metagenomic next-generation sequencing in a kidney transplant recipient: A case report.
Pulmonary nocardiosis is difficult to diagnose by culture and other conventional testing, and is often associated with lethal disseminated infections. This difficulty poses a great challenge to the timeliness and accuracy of clinical detection, especially in susceptible immunosuppressed individuals. Metagenomic next-generation sequencing (mNGS) has transformed the conventional diagnosis pattern by providing a rapid and precise method to assess all microorganisms in a sample. A 45-year-old male was hospitalized for cough, chest tightness and fatigue for 3 consecutive days. He had received a kidney transplant 42 d prior to admission. No pathogens were detected at admission. Chest computed tomography showed nodules, streak shadows and fiber lesions in both lung lobes as well as right pleural effusion. Pulmonary tuberculosis with pleural effusion was highly suspected based on the symptoms, imaging and residence in a high tuberculosis-burden area. However, anti-tuberculosis treatment was ineffective, showing no improvement in computed tomography imaging. Pleural effusion and blood samples were subsequently sent for mNGS. The results indicated Nocardia farcinica as the major pathogen. After switching to sulphamethoxazole combined with minocycline for anti-nocardiosis treatment, the patient gradually improved and was finally discharged. A case of pulmonary nocardiosis with an accompanying bloodstream infection was diagnosed and promptly treated before the dissemination of the infection. This report emphasizes the value of mNGS in the diagnosis of nocardiosis. mNGS may be an effective method for facilitating early diagnosis and prompt treatment in infectious diseases, which overcomes the shortcomings of conventional testing.


Epidermolysis Bullosa: A Case of Successful Total Hip Arthroplasty.
Epidermolysis bullosa (EB) is a rare dermatological disease in which patients suffer from skin fragility and blisters. One of the major complications is the development of skin infections, which may preclude surgical intervention. We present a case of a 49-year-old female with a past medical history of EB, who presented to the emergency department (ED) with right groin pain of one-hour duration after falling on her right side. The patient underwent a successful open reduction and internal fixation for her right hip without complications. Over the course of three months after the procedure, she experienced worsening of the pain accompanied by skin necrosis and total collapse of the femoral head. Subsequent total hip replacement surgery was performed using a cementless (Zimmer, Warsaw, IN) prosthesis and fixated via cannulated screws. To decrease the risk of infection, IV cefazolin was given as a prophylactic antibiotic preoperatively. Vancomycin IV and imipenem/cilastatin IV were given for four days postoperatively. We made sure that our patient is experiencing the least possible pain by giving sufficient analgesics after the surgery. We used morphine, paracetamol, and gabapentin for pain control. For 25 days after the surgery, the patient did not complain of any pain. Upon follow-up, sutures were removed, and no surgical wound infection, rashes, or lacerations were noted. We encourage orthopedic surgeons dealing with patients suffering from dermatological conditions with fragile skin such as EB and decreased level of activity that requires total hip arthroplasty to proceed with the surgical intervention after considering adequate infection control to improve quality of life.


[Epidemiological study on disabilities among ethnic minorities in China].
To explore the prevalence rates of disabilities among the ethnic minority people in China. Utilizing stratified, multiphase, and cluster probability sampling design, 2 526 145 persons were investigated and screened by trained interviewers, including 297 761 persons with ethnic minority backgrounds. Respondents scoring positive for potential problems were referred to physician for further diagnosis on disability and on scale measurement. The overall prevalence rate of disability for both ethnic minority and Han population were 6.24% (95%CI: 6.16% - 6.51%) and 6.41% (95%CI: 6.38% - 6.51%) respectively. The total aggregate age-adjusted prevalence rate of disability was 7.31% for persons with ethnic minority. The prevalence rate of disabilities in male was significantly higher than that in females (7.31% vs. 6.75%). The ranking of prevalence rates on different type of disabilities were: physical disability 1.90% (95%CI: 1.89% - 1.91%), hearing disability 1.34% (95%CI: 1.33% - 1.35%), multiple disability 1.14% (95%CI: 1.13% - 1.15%), vision disability 0.99% (95%CI: 0.97% - 1.01%), psychiatric disability 0.38% (95%CI: 0.37% - 0.40%), intellectual disability 0.38% (0.37% - 0.39%) and speech disability 0.12% (0.11% - 0.13%). Cerebral Palsy, genetic diseases, tympanitis, cerebral disease and mental retardation (not including unknown items) were the major causes for disabled children with ethnicity background. Degenerated diseases, including osteoarthropathy, cerebrovascular disease, elderly-related deafness or cataract were most important causes for ethnic minority persons aged 60 or over. Injury, including traffic accident was important disabled-related factor for persons with minority ethnicity aged 15 - 59. The main causes and ranking of causes for ethnical minority were similar with that for Han population. The prevalence rate of disability for ethnic minority persons was significantly higher than that for Han population in China. Prevention for different types of disability should be provided accordingly to persons with ethnic minority, in different age groups.


A randomised comparative study of Miller laryngoscope blade versus Oxiport® Miller laryngoscope blade for neonatal and infant intubations.
Neonates and infants are prone to oxygen desaturation during the induction of general anaesthesia. Pharyngeal oxygen insufflation has been shown to delay the onset of desaturation and hypoxaemia during apnoea. We tested the hypothesis that deep laryngeal oxygenation with Oxiport® Miller blade would delay the onset of desaturation compared to laryngoscopy without supplemental oxygen (Miller blade). One hundred neonates and infants undergoing general anaesthesia with endotracheal intubation for surgery were recruited and randomly assigned to one of the two groups: Miller or Oxiport group (laryngoscopy performed with Miller or Oxiport® blade, respectively). Primary outcome measure was the lowest oxygen saturation (SpO2) attained during intubation. Secondary outcomes were the incidence of severe desaturation (SpO2< 85%), correlation between SpO2and time to intubation in each group. Pearson's correlation coefficient was used to measure the correlation between time to intubation and desaturation in each group. P < 0.05 was considered statistically significant. Data from 95 patients were available for the final analysis: Miller group (n = 48) and Oxiport group (n = 47). Mean lowest SpO2was 95.9% ± 5.75% in Miller group and 97.55% ± 2.93% in Oxiport group (P = 0.049). Correlation between time to intubation and SpO2was -0.110; P = 0.459 in Miller group and -0.468; P = 0.001 in Oxiport group. Severe desaturation occurred in 12.5% patients in Miller group and none in Oxiport group. Apnoeic laryngeal oxygen insufflation with Oxiport® laryngoscope blade decreases the incidence of severe desaturation during neonatal and infant intubations.


Public-private partnerships in fostering outer space innovations.
As public and private institutions recognize the role of space exploration as a catalyst for economic growth, various areas of innovation are expected to emerge as drivers of the space economy. These include space transportation, in-space manufacturing, bioproduction, in-space agriculture, nuclear launch, and propulsion systems, as well as satellite services and their maintenance. However, the current nature of space as an open-access resource and global commons presents a systemic risk for exuberant competition for space goods and services, which may result in a "tragedy of the commons" dilemma. In the race among countries to capture the value of space exploration, NASA, American research universities, and private companies can avoid any coordination failures by collaborating in a public-private research and development partnership (PPRDP) structure. We present such a structure founded upon the principles of polycentric autonomous governance, which incorporate a decentralized autonomous organization framework and specialized research clusters. By advancing an alignment of incentives among the specified participatory members, PPRDPs can play a pivotal role in stimulating open-source research by creating positive knowledge spillover effects and agglomeration externalities as well as embracing the nonlinear decomposition paradigm that may blur the distinction between basic and applied research.


Role of Sigma Receptors in Alcohol Addiction.
Pharmacological treatments for alcohol use disorder (AUD) are few in number and often ineffective, despite the significant research carried out so far to better comprehend the neurochemical underpinnings of the disease. Hence, research has been directed towards the discovery of novel therapeutic targets for the treatment of AUD. In the last decade, the sigma receptor system has been proposed as a potential mediator of alcohol reward and reinforcement. Preclinical studies have shown that the motivational effects of alcohol and excessive ethanol consumption involve the recruitment of the sigma receptor system. Furthermore, sigma receptor antagonism has been shown to be sufficient to inhibit many behaviors related to AUDs. This paper will review the most current evidence in support of this receptor system as a potential target for the development of pharmacological agents for the treatment of alcohol addiction.


Sildenafil for primary and secondary pulmonary hypertension.
Sildenafil is a selective inhibitor of cyclic guanosine monophosphate-specific phosphodiesterase type 5, an enzyme that is abundant in both lung and penile tissues. Sildenafil is widely used to dilate penile arteries, suggesting that it may also dilate pulmonary arteries in patients with pulmonary hypertension. However, the long-term hemodynamic effects and safety of the drug in pulmonary hypertension are not known. One patient with primary pulmonary hypertension and another with secondary pulmonary hypertension caused by collagen disease were given 50 mg oral sildenafil during cardiac catheterization for assessment of the acute hemodynamic effects of the drug. The patients were then given maintenance treatment with 25 mg oral sildenafil twice a day. Long-term hemodynamic effects were evaluated by repeated cardiac catheterization after 3 months, with the last oral dose given 15 hours before the procedure. The acute hemodynamic effects of sildenafil after the long-term treatment were studied during the same cardiac catheterization. Sildenafil did not affect aortic pressure, but it significantly decreased pulmonary artery pressure and increased cardiac index, thereby reducing pulmonary vascular resistance. Long-term maintenance therapy with 25 mg oral sildenafil twice a day remarkably improved the clinical condition of the patients, without causing any adverse effects; New York Heart Association functional classification returned to class II (from class III). The acute efficacy of sildenafil was well preserved after the long-term treatment; there was no tolerance. The data strongly suggest that sildenafil can be used as a valuable pulmonary vasodilator in patients with pulmonary hypertension, with good long-term hemodynamic effects and safety. The results necessitate larger trials to confirm these observations in a larger cohort of patients.


[Local treatment of obstructive uric acid calculi].
Dissolution of uric acid calculi could be obtained by oral or parenteral urinary alcalinization, but this method cannot apply to the case of obstructive calculi. Nineteen obstructive calculi in 18 patients were treated by in situ alcalinization through a percutaneous nephrostomy catheter (PCN). Eight patients were initially anuric, 7 of whom from an obstructed solitary kidney and 1 from a bilateral obstructive lithiasis. Fifteen calculi were located in the ureter, 3 in the uretero-pelvic junction and 1 in the pelvis. After 48 h of urinary diversion through PCN, an isotonic sodium bicarbonate solution (14 g %) was continuously infused at an average flow rate of 2.8 l/24 h, through either an unique PCN, or a 2 PCN-irrigation circuit in the 7 cases with permanently obstructive calculus. Fifteen calculi (80%) were completely dissolved after 3 to 13 days of alcalinization (average 5.8 days). One large calculus was reduced by 3/4 and further removed by percutaneous lithotripsy. Three patients underwent ureterotomy after 9 to 11 days of uneffective treatment. Local alcalinization is an effective and non invasive treatment for obstructive uric acid calculi, and is logically associated with the necessary urinary diversion.


Regulation of gene expression in lectin-stimulated or lymphokine-stimulated T lymphocytes. Effects of cyclosporine.
The effects of cyclosporine were examined on gene expression induced in T lymphocytes by mitogenic lectins and interleukin 2 (IL-2). Used at concentrations that inhibited proliferation of human peripheral blood lymphocytes by approximately 90%, CsA suppressed, to different extents, the phytohemagglutinin-stimulated expression of various genes, with levels of mRNAs for IL-2 being inhibited by approximately 100%, c-myc and N-ras by approximately 80%, and c-fos and IL-2 receptors by approximately 50%. Comparisons of the actions of CsA on gene expression in a cloned murine T cell (L2), stimulated with concanavalin A or IL-2, demonstrated that CsA specifically blocked the accumulation of mRNAs for the c-myc and p53 protooncogenes when induced by Con A, but not when induced by IL-2. Taken together, these findings indicate that several pathways can control the expression of a particular gene, and suggest that CsA interferes with only some of these regulatory pathways of gene expression in T lymphocytes.


[Carfilzomib, lenalidomide and dexamethasone in relapsed/refractory multiple myeloma patients: the real-life experience].
Carfilzomib, lenalidomide, and dexamethasone (KRd) have been approved for the treatment of relapsed and refractory multiple myeloma (RRMM) based on ASPIRE clinical trial. Analysis of efficacy and safety of KRd in routine clinical practice. The prospective analysis included patients with MM who received at least one line of previous therapy. The inclusion criteria were relapse/progression; refractoriness; lack of very good partial response (VGPR) and more after the first line of therapy. Since February 2016, we used KRd like in ASPIRE trial, since October 2019, carfilzomib has been used at a dose of 56 mg/m2 on days 1, 8 and 15. Autologous hematopoietic stem cell transplantation (autoHSCT), consolidation (KRd) and maintenance therapy (Rd) were regarded as one line of therapy. We evaluated 77 patients with median age at the time of diagnosis is 55 (3072) years. For 56% (n=43) of patients KRd was applied as the second line (group 1), for 44% (n=34) as the third and more (group 2). In 23/43 patients from group 1, an early change in therapy was made due to insufficient effectiveness (after 24 courses of VCD or PAD). KRd served as a "bridge" to autoHSCT in 25 (32%) patients (21 of 25 in group 1). Another 7 patients underwent collection of autoHSC (all from group 1). The overall response rate (ORR) was 80.5%, with 33.8% complete response (CR) and 26% VGPR. ORR in group 1 was 98% versus 65.6% in group 2; 24-month overall survival (OS) was 70%, progression free survival (PFS) 49.8%. In group 1, 24-month OS was 85.6% versus 50.0% in group 2, 24-month PFS was 67.8% versus 25.5% (p=0.01). Our analysis confirmed the high efficiency of KRd in the treatment of RRMM in real-life practice. Early correction of therapy with insufficient effectiveness of the first line made it possible to implement the strategy of high-dose consolidation and autoHSCT in a larger percentage of patients with MM.


Nuclear factor-kappaB as a potential therapeutic target for the novel cytotoxic agent LC-1 in acute myeloid leukaemia.
Nuclear factor-kappaB (NF-kappaB) has been implicated in a number of malignancies and has been suggested to be a potential molecular target in the treatment of leukaemia. This study demonstrated the constitutive activation of NF-kappaB in human myeloid blasts and a clear correlation between NF-kappaB expression and in vitro cytoprotection. High NF-kappaB expression was found in many of the poor prognostic acute myeloid leukaemia (AML) subtypes, such as French-American-British classification M0 and M7, and the poor cytogenetic risk group. The in vitro effects of LC-1, a novel dimethylamino-parthenolide analogue, were assessed in 62 primary untreated AML samples. LC-1 was found to be cytotoxic to AML cells in a dose-dependent manner, mediated through the induction of apoptosis. The median drug concentration necessary to kill 50% of the cells was 4.5 micromol/l for AML cells, compared with 12.8 micromol/l for normal marrow cells. LC-1 was shown to reduce the five individual human NF-kappaB Rel proteins in a dose-dependent manner. The subsequent inhibition of many NF-kappaB-regulated cytokines was also demonstrated. Importantly, sensitivity to LC-1 was correlated with the basal NF-kappaB activity. Consequently, LC-1 treatment provides a proof of principle for the use of NF-kappaB inhibitors in the treatment of AML.


Plasma membrane changes in freeze-fractured rat kidney cortex following renal ischemia.
Ischemia was produced in the inner cortex of the rat kidney by clamping the pedicle (artery, vein, and ureter) and severing collateral connections. After 30 minutes of ischemia, a slight aggregation of membrane-associated particles was observed in the freeze-fractured plasma membranes. The aggregation was progressive after 60 and 120 minutes of ischemia. These changes were reversible after 15 and 240 minutes of reflow of blood following 30 or 60 minutes of ischemia. The changes were irreversible after 120 minutes of ischemia. The cells were vacuolated after ischemic periods of 30 minutes or longer and after 120 minutes of ischemia the tissue was severely damaged and aggregation of membrane-associated particles was evident in the vacuolar membranes. No changes in the tissue or plasma membrane were observed after 5 or 20 minutes of ischemia.


Health-related quality of life in ANCA-associated vasculitis and item generation for a disease-specific patient-reported outcome measure.
The antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAVs) are multisystem diseases of the small blood vessels. Patients experience irreversible damage and psychological effects from AAV and its treatment. An international collaboration was created to investigate the impact of AAV on health-related quality of life (HRQoL), and develop a disease-specific patient-reported outcome measure to assess outcomes of importance to patients. Patients with AAV from the UK, USA, and Canada were interviewed to identify salient aspects of HRQoL affected by AAV. The study was overseen by a steering committee including four patient research partners. Purposive sampling of interviewees ensured representation of a range of disease manifestations and demographics. Inductive analysis was used to identify themes of importance to patients; these were further confirmed by a free-listing exercise in the US. Individual themes were recast into candidate items, which were scrutinized by patients, piloted through cognitive interviews and received a linguistic and translatability evaluation. Fifty interviews, conducted to saturation, with patients from the UK, USA, and Canada, identified 55 individual themes of interest within seven broad domains: general health perceptions, impact on function, psychological perceptions, social perceptions, social contact, social role, and symptoms. Individual themes were constructed into >100 candidate questionnaire items, which were then reduced and refined to 35 candidate items. This is the largest international qualitative analysis of HRQoL in AAV to date, and the results have underpinned the development of 35 candidate items for a disease-specific, patient-reported outcome questionnaire.


Validity of ActiGraph child-specific equations during various physical activities.
The purpose of this study was to examine the validity of seven child-specific ActiGraph prediction equations/cut points (Crouter vector magnitude two-regression model [Cvm2RM], Crouter vertical axis two-regression model [Cva2RM], Freedson child equation, Treuth equation, Trost equation, Puyau equation, and Evenson equation) for estimating energy expenditure and time spent in sedentary behaviors, light physical activity (LPA), moderate physical activity (MPA), and vigorous physical activity (VPA). Forty boys and 32 girls (mean ± SD; age = 12 ± 0.8 yr) participated in the study. Participants performed eight structured activities and approximately 2 h of free-living activity. Activity data were collected using an ActiGraph GT3X+, positioned on the right hip, and energy expenditure (MET(RMR); activity VO(2) divided by resting VO(2)) was measured using a Cosmed K4b(2). ActiGraph prediction equations were compared against the Cosmed for MET(RMR) and time spent in sedentary behaviors, LPA, MPA, VPA, and moderate and vigorous physical activity. For the structured activities, all prediction methods were significantly different from measured MET(RMR) for three activities or more (P < 0.05); however, all provided close estimates of MET(RMR) during walking. On average, participants were monitored for 95.0 ± 36.5 min during the free-living measurement. The Cvm2RM and the Puyau methods were within 0.9 MET(RMR) of measured free-living MET(RMR) (P > 0.05); all other methods significantly underestimated measured MET(RMR) (P < 0.05). The Cva2RM was within 9.7 min of measured time spent in sedentary behaviors, LPA, MPA, and moderate and vigorous physical activity, which was the best of the methods examined. All prediction equations underestimated VPA by 6.0-13.6 min. Compared with the Cosmed, the Cvm2RM and the Puyau methods provided the best estimate of MET(RMR) and the Cva2RM provided the closest estimate of time spent in each intensity category during the free-living measurement. Lastly, all prediction methods had large individual prediction errors.


SKIN DOSE MAPPING IN INTERVENTIONAL CARDIOLOGY: A PRACTICAL SOLUTION.
Numerous cases of radiation-induced tissue reactions following interventional cardiology (IC) procedures have been reported, resulting in the need for an optimized and personalized dosimetry. At present, there are many fluoroscopy units without Digital Imaging and Communications in Medicine (DICOM) Radiation Dose Structured Report globally installed. Many of these have not been updated yet, and may never be, therefore, the main objectives of this paper are to develop an offline skin dose mapping application, which uses DICOM headers for the peak skin dose (PSD) assessment and to compare the PSD assessment results to XR-RV3 Gafchromic film for common IC procedures. The mean deviation between the measured and the calculated PSD was 8.7 ± 26.3%. Simulated skin dose map showed good matching with XR-RV3 Gafchromic film. The skin dose mapping application presented in this paper is an elegant solution and a suitable alternative to XR-RV3 Gafchromic film.


Lipocalin-2 and iron trafficking in the tumor microenvironment.
Iron is an essential element for virtually all organisms. It facilitates cell proliferation and growth but also contributes to major hallmarks of cancer such as tumor initiation, growth, and metastasis. Often, iron handling of tumor cells is disturbed, with altered iron acquisition, efflux, and storage. Targeting perturbed iron metabolic pathways might open opportunities towards novel approaches in cancer treatment. It is becoming clear that cells of the tumor microenvironment such as macrophages contribute to tumor progression. Since macrophages evolved a multitude of mechanisms to sequester, transport, store, and release iron it can be speculated that tumor cells educate them to supply iron to support tumor growth. Recent evidence supports the existence of transferrin-independent iron transport mechanisms in the tumor microenvironment, which points to local iron transport proteins such as lipocalin-2 and/or low molecular weight iron-trafficking substances such as siderophores. We hypothesize that tumor cells educate immune cells, i.e. macrophages in their neighborhood to make them delivering iron for the benefit of cancer progression. In particular, we pay attention to recent developments, pointing to lipocalin-2 and siderophores as alternative iron transport molecules in the tumor microenvironment.


Hypomethylation and the Resultant Overexpressed PARM1: a Biomarker for Poor Prognosis of Diffuse Large B-cell Lymphoma.
Prostate androgen-regulated mucin-like protein (PARM1) is known to promote cell survival via protecting the cell surface, thus being involved in cancer development. The Gene Expression Profiling Interactive Analysis (GEPIA), MEXPRESS database, LinkedOmics database, GeneMANIA database, and the Tumor Immune Estimation Resource (TIMER) database were accessed to explore the epigenetic regulation, prognostic value, biological functions and mechanisms of PARM1 in diffuse large B-cell lymphoma (DLBCL). Hypomethylation and resultant overexpression of PARM1 was found in DLBCL. The high-level expression of PARM1 was related to the poor outcome of DLBCL patients. PARM1 participated in DNA repair, cell cycle, and cellular response to stress. PARM1 was also associated with autophagy, apoptosis, Ras pathway, and MAPK cascade. Significant kinase targets of PARM1 included ATM, CDK1, and CDK2. Significant transcription factor targets of PARM1 involved ELK1, MYC and so on. Significant miRNA targets of PARM1 included miR21, miR202, miR323, and miR345. Further analysis suggested that the PARM1 regulated autophagy through the PI3K-Akt signaling. PARM1 was found to be correlated with immune cell infiltration, which indicated the important roles of PARM1 in microenvironment of DLBCL. Our study lays a foundation for further research on the impact of PARM1 in DLBCL tumorigenesis and precision therapy.


Effects of wearing the Bausch & Lomb SoflensTM while skydiving.
The use of Soflenses as a method of ametropic correction and ocular protection while skydiving is explored. The use of the Soflens with and without the addition of protective goggles is compared. Vision is seen to be relatively stable and clear while jumping with the Soflens, yet stability and clarity improve significantly when protective goggles are worn over the Soflenses. Stability and clarity improve significantly when protective turbulence in the facial area increases due to more involved skydiving maneuvers. A definite short-term corneal epithelial disturbance is observed when lenses are blown off the eyes due to wind turbulence.


Occurrence of heterogenous forms of the subunits of creatine kinase in various muscle and nonmuscle tissues and their behaviour during myogenesis.
Purified, homodimeric creatine kinases from chicken were subjected to two-dimensional gel analysis under dissociating conditions. Each of the subunits M-creatine kinase and B-creatine kinase was resolved into a basic and an acidic subspecies with very similar mobilities in the sodium dodecylsulfate dimension. The M-creatine kinase subspecies were found in myogenic cells, fast muscle, slow muscle and the B-creatine kinase subspecies were present in heart, gizzard and brain. The creatine kinase subunits were identified in these tissues by a variety of methods like immunoreplicas of two-dimensional gels, immunoprecipitations, or coelectrophoresis with purified creatine kinase and all gave the same results. In the course of myogenic development in vitro the subspecies were synthesized coordinately and no indication was found for a differential regulation of any of the subspecies of the creatine kinase subunits. No radioactive phosphorus was incorporated into either one of the subspecies, hence phosphorylation could be ruled out as the source of heterogeneity. Furthermore, peptide mapping analysis of partial proteolytic digests did not reveal differences among the subspecies of the same subunit. Not only chicken but also rat creatine kinase displayed this type of heterogeneity. All subspecies were observed after translation of chicken RNA in a cell-free protein-synthesizing system. The heterogeneity probably might best be explained by the existence of multiple, but closely related genes for the creatine kinase subunits.


Silibinin synergizes with histone deacetylase and DNA methyltransferase inhibitors in upregulating E-cadherin expression together with inhibition of migration and invasion of human non-small cell lung cancer cells.
Aggressive cancers in the epithelial-to-mesenchymal transition (EMT) phase are characterized by loss of cell adhesion, repression of E-cadherin, and increased cell mobility. Non-small cell lung cancer (NSCLC) differs in basal level of E-cadherin; predominantly exhibiting silenced expression due to epigenetic-related modifications. Accordingly, effective treatments are needed to modulate these epigenetic events that in turn can positively regulate E-cadherin levels. Herein, we investigated silibinin, a natural flavonolignan with anticancer efficacy against lung cancer, either alone or in combination with epigenetic therapies to modulate E-cadherin expression in a panel of NSCLC cell lines. Silibinin combined with HDAC inhibitor Trichostatin A [TSA; 7-[4-(dimethylamino)phenyl]-N-hydroxy-4,6-dimethyl-7-oxohepta-2,4-dienamide] or DNMT inhibitor 5'-Aza-deoxycytidine (Aza) significantly restored E-cadherin levels in NSCLC cells harboring epigenetically silenced E-cadherin expression. These combination treatments also strongly decreased the invasion/migration of these cells, which further emphasized the biologic significance of E-cadherin restoration. Treatment of NSCLC cells, with basal E-cadherin levels, by silibinin further increased the E-cadherin expression and inhibited their migratory and invasive potential. Additional studies showed that silibinin alone as well as in combination with TSA or Aza downmodulate the expression of Zeb1, which is a major transcriptional repressor of E-cadherin. Overall these findings demonstrate the potential of combinatorial treatments of silibinin with HDAC or DNMT inhibitor to modulate EMT events in NSCLC cell lines, leading to a significant inhibition in their migratory and invasive potentials. These results are highly significant, since loss of E-cadherin and metastatic spread of the disease via EMT is associated with poor prognosis and high mortalities in NSCLC.


Silencing mitogen-activated protein kinase-activated protein kinase-2 arrests inflammatory bone loss.
p38 mitogen-activated protein kinases (MAPKs) are critical for innate immune signaling and subsequent cytokine expression in periodontal inflammation and bone destruction. In fact, previous studies show that systemic p38 MAPK inhibitors block periodontal disease progression. However, development of p38 MAPK inhibitors with favorable toxicological profiles is difficult. Here, we report our findings regarding the contribution of the downstream p38 MAPK substrate, mitogen-activated protein kinase-activated protein kinase 2 (MK2 or MAPKAPK-2), in immune response modulation in an experimental model of pathogen-derived lipopolysaccharide (LPS)-induced periodontal bone loss. To determine whether small interfering RNA (siRNA) technology has intraoral applications, we initially validated MK2 siRNA specificity. Then, gingival tissue surrounding maxillary molars of rats was injected with MK2 siRNA or scrambled siRNA at the palatal regions of bone loss. Intraoral tissues treated with MK2 siRNA had significantly less MK2 mRNA expression compared with scrambled siRNA-treated tissues. MK2 siRNA delivery arrested LPS-induced inflammatory bone loss, decreased inflammatory infiltrate, and decreased osteoclastogenesis. This proof-of-concept study suggests a novel target using an intraoral RNA interference strategy to control periodontal inflammation.


The presence of two neuraminidases in an influenza virus.
The wild type influenza strain A/Aichi/2/68 (H3N2), when disrupted with SDS and electrophoresed on cellulose acetate paper, yielded two separate neuraminidases, NA(H+) and NA(H-). These enzymes after extraction were biologically active and possessed different specific activities. Enzyme NA(H+) possessed neuraminidase as well as hemagglutinin activities whereas enzyme NA(H-) demonstrated only neuraminidase activity. Similar results were obtained when the Aichi strain was treated with Tween-ether and the two enzymes were separated by affinity chromatography. Techniques used failed to separate the hemagglutinin activity from neuraminidase NA(H+). These results suggest that the dual activity present in enzyme NA(H+) may be characteristic of this protein. Both enzymes are antigenically different and are apparently present as distinct entities in the Aichi strain. Experiments showed that only enzyme NA(H-) of the Aichi strain was incorporated into the hybrid X-32 virus during genetic recombination.


Distribution of human papillomavirus genotypes in women with cervical alterations from north Argentina.
Cervical cancer remains a major public health problem in northern Argentina, showing the highest mortality rate in the country (approximately 22 cases/100000 women). The aim of this study was to provide epidemiological data on the prevalence and type distribution of human papillomavirus (HPV) in women with pre-neoplastic lesions before the massive introduction of HPV vaccination in the country. Exfoliated cervical cells were collected to screen for HPV using the widely known MY09/11 PCR, followed by the restriction fragment-length polymorphism (RFLP) technique from a total of 714 women with previously diagnosed atypical squamous cells of undetermined significance (ASCUS), low-grade squamous intraepithelial lesion (LG-SIL) and high-grade squamous intraepithelial lesion (HG-SIL). Overall HPV prevalence was 48.2% in ASCUS (24 different HPV types detected), 66.5% in LG-SIL (37 HPV types detected) and 82.6% in HG-SIL (16 HPV types detected). HPV-16 was the most prevalent type among all cases. With respect to multiple HPV infections, 9.6% were observed in ASCUS, 14.3% in LG-SIL and 11.4% in HG-SIL. The major strength of our study is the assessment of a large series of women with cytological alterations in this region. The information attained will be useful as a regional baseline for future epidemiological vigilance, in the context of the national HPV vaccination program.


Vulnerability: reflection on its ethical implications for the protection of participants in SAMHSA programs.
The vulnerability of participants in Substance Abuse and Mental Health Services Administration (SAMHSA) programs is a consequence of the illnesses that they are experiencing; ethical guarantees must be in place that ensure the dignity of the persons involved in such programs. Dignity is more than an individual concern; it has individual, institutional, and societal dimensions. An ethical framework is proposed that involves the interrelated vulnerabilities and needs of individuals and communities and our societal response to them. Among the issues given particular attention are individual and community stigmatization, target population involvement in program planning, balance with regard to confidentiality and privacy, the place of proportionality grounded in a rich sense of community as a guiding ethical priniciple, and guidelines for SAMHSA programs.


A structured approach to medical management: a psychosocial intervention to support pharmacotherapy in the treatment of alcohol dependence.
Given the national trend toward integrating substance abuse treatment into medical practice, experts in the field of alcoholism designed a psychosocial, medically based intervention to be used with pharmacotherapy in the COMBINE multisite national study, supported by the National Institute on Alcohol Abuse and Alcoholism. A main purpose of the COMBINE Study is to investigate optimal treatment for patients with alcohol dependence by combining pharmacotherapy and psychosocial interventions. The medically based intervention, called Medical Management (MM), was specifically constructed to be implemented by medically trained practitioners in nonspecialty settings. Each visit includes evaluations of medication safety and adherence, monitoring of alcohol use and direct advice to the patient for achieving full recovery. There are several themes implicit in MM. Patient education about the disorder and about the treatment being provided are both essential. The clinician also educates the patient about how he or she has been affected by alcohol dependence. Information is given on how to take the medication(s) as prescribed, what the patient should expect from the medication(s) and what kinds of events the clinician will need to know about during treatment. Finally, the clinician and patient discuss strategies for ensuring medication safety and adherence to the prescribed regimen. MM was easily implemented in the COMBINE Study with the aid of the MM Treatment Manual.


Revealing the biography of a hidden medieval manuscript using synchrotron and conventional imaging techniques.
Reading the content of hidden texts from ancient manuscripts has become an increasingly important endeavor thanks to the variety of non-destructive analytical tools and image processing routines available for this task. In this study, portable macro X-Ray Fluorescence (MA-XRF-tube), Visible Hyperspectral Imaging (HSI) together with Synchrotron based macro X-Ray Fluorescence (MA-XRF-SR) are combined with signal processing methods to reveal the biography of a degraded manuscript recycled as binding material for a 16th century printed edition of Hesiod's Works and Days. The analytical techniques allow visualizing the hidden text, revealing passages from the Institutes Justinian, a 6th century A.D codification of the Roman Law, with further marginal comments on medieval Canon Law. In addition, the identification of the materials (e.g. pigments, inks) part of the original manuscript together with their sequence of use are revealed: i) the preparation of the parchment using a Ca-based preparation layer, ii) drawing of ruled guide lines, using a Pb-based pen or ink, iii) writing of the main text using a rich Fe-gall ink with modulating color pigments (Hg-, Cu- and Pb- based) and iv) addition of two types of comments to the main text, one of the ink used for the comments being a Fe-gall ink rich in Cu.


Route to Substituted Furan-2(5H)-ones from cyclo-Alkenecarboxylic Acids and Acrylates via C-H Activation.
Under rhodium(III) catalysis, four kinds of cycloalkenecarboxylic acids successfully reacted with acrylates via direct activation of the β-alkenyl C-H bond. The present protocol provides the facile and highly efficient synthesis of substituted furan-2(5H)-ones from readily available starting materials with moderate to good yields. In addition, their possible reaction mechanisms were also discussed.


Ligand Bent-Angle Engineering for Tuning Topological Structures and Acetylene Purification Performances of Copper-Diisophthalate Frameworks.
To enrich structural chemistry and widen the application prospects of MOFs (metal-organic frameworks), the development of a synthetic strategy to realize structural and functional modulation is highly demanded. By implementation of the linker bent-angle engineering strategy, three banana-like diisophthalate linkers with distinct bent angles were designed and synthesized. The inclusion of the targeted linkers into MOFs through solvothermal assembly with CuCl2·2H2O under identical conditions yielded three crystalline solids featuring diversified topological structures as revealed by X-ray crystallographic studies. Furthermore, functional explorations indicated that they are promising solid adsorbents for acetylene (C2H2) purification application with structurally dependent separation potentials. The results reported in this study illustrated a rare example of modulating the topological structures and separation efficiencies of MOFs by engineering the ligand bent angles.


Survival after radiofrequency ablation and/or chemotherapy for lung cancer and pulmonary metastases: a systematic review and meta-analysis.
Radiofrequency ablation (RFA) and chemotherapy are used to treat lung cancer or pulmonary metastases, but no direct comparison of overall survival (OS) has been published. The present study aimed to assess the OS of RFA and/or chemotherapy in patients with lung cancer or pulmonary metastases who were not candidates for surgical resection. To identify relevant studies, the following databases were electronically searched from their inception to 31 March 2023: PubMed, Embase, Web of Science, Cochrane Library, Scopus, Ovid, ScienceDirect, SinoMed, China National Knowledge Infrastructure Database, Chongqing VIP Chinese Science and Technology Periodical Database, Wanfang Database, LILACS, ClinicalTrials.gov, and Chictr.org. Manual retrieval was also conducted. We used published hazard ratios (HRs) if available or estimates from other survival data. A total of 1,387 participants from 14 trials were included in the final analysis. Patients treated with RFA combined with chemotherapy significantly improved OS compared with those treated with chemotherapy alone [HR 0.50, 95% confidence interval (CI) 0.41-0.61; p < 0.00001], with an absolute difference at 12 months of 29.6% (95% CI 23.7-35.5), at 24 months of 19.2% (95% CI 10.1-28.2), and at 36 months of 22.9% (95% CI 12.0-33.7). No statistically significant difference was observed in the subgroups of case type, cancer type, chemotherapy drugs, and tumor size. The HR for OS with RFA plus chemotherapy vs. RFA alone was 0.53 (95% CI 0.41-0.70; p < 0.00001), corresponding to a 27.1% (95% CI 18.3-35.8), 31.0% (95% CI 19.9-41.9), and 24.9% (95% CI 15.0-34.7) absolute difference in survival at 12 months, 24 months, and 36 months, respectively. Subgroup analysis by geographic region and TNM stage showed that RFA combined with chemotherapy still significantly improved OS compared to RFA. The HR of RFA vs. chemotherapy was 0.98 (95% CI 0.60-1.60; p = 0.94), with an absolute difference at 12 months of 1.4% (95% CI -19.2 to 22.1), at 24 months of 7.8% (95% CI -11.3 to 26.8), and at 36 months of 0.3% (95% CI -13.2 to 13.8). The overall indirect comparison of OS for RFA vs. chemotherapy was 0.95 (95% CI 0.72-1.26; p = 0.74). Data on progression-free survival were not sufficiently reported. RFA combined with chemotherapy might be a better treatment option for patients with lung cancer or pulmonary metastases than chemotherapy alone or RFA alone. The comparison between RFA and/or chemotherapy remains to be specifically tested. https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=335032, identifier CRD42022335032.


[The significance of cardiovascular risk factors and C-reactive protein to the development of atherosclerosis in women with systemic lupus erythematosus].
Compared with general population, women suffering from systemic lupus erythematosus (SLE) have signs of coronary artery disease (CAD) five to eight times more often, especially in young age. Early development of atherosclerosis in patients with SLE is caused by conventional cardiovascular risk factors and specific ones, associated with the disease and its therapy. A slight increase in such an inflammatory marker as C-reactive protein (CRP) is thought to reflect the presence of subclinical inflammation in the vascular wall, connected with atherosclerotic process. The authors analyzed the frequency of clinical and subclinical (an increase in the thickness of intima-media complex (IMC)) atherosclerotic manifestations, the summary coronary risk, the prevalence of conventional risk factors, and CRP level in 133 female patients with SLE and in 50 healthy donors. Compared to the control group, SLE patients were younger, developed cardiovascular diseases (CAD, stenocardia, myocardial infarction, and cerebral stroke (p = 0.05) as well as arterial hypertension more often, had higher levels of hs-CRP and triglycerides, and lower levels of high density lipoprotein cholesterol (HDLC). There was a positive correlation between hs-CRP level and the activity of the disease according to ECLAM score, ES value, IgG and IgM levels, hematological disturbances (anemia, leucopenia, and/or thrombocytopenia) , and a negative correlation with total cholesterol level, HDLC there was a moderate correlation between hs-CRP and a maximal IMC value.


Revised equations allowing the estimation of the uncertainty associated with the Total Body Water version of the Widmark equation.
Widmark calculations are the most commonly used alcohol calculations to estimate a) the amount of alcohol consumed based on blood alcohol concentration (BAC) and b) BACs at a set time after consumption of a known amount of alcohol. These calculations are vital in forensic casework. Previous work has demonstrated that using general error propagation-based equations the variability associated with alcohol calculations can be estimated, but these equations have only been determined for the volume of distribution version of the Widmark equation. However, recent investigations have shown that the total body water (TBW) version of the Widmark equation is more reliable than the version that utilizes the apparent volume of distribution of ethanol. To date, there is no general error propagation equation to determine the variability associated the TBW version of the Widmark equation. Using previously published studies of 185 individuals in which alcohol elimination rate (β) and ethanol's volume of distribution were determined, we have shown that there is a negative correlation (-0.247) between the alcohol elimination rate (β) and TBW. Using these data, we were able to produce equations allowing the estimation of the variability of the results calculated using the TBW version of the Widmark equation. This will allow forensic practitioners to give the best determination of the variability associated with Widmark calculations currently possible.


Clinical Analysis of Pulmonary Nocardiosis in Patients With Autoimmune Disease.
Nocardiosis is an opportunistic infection that most commonly involves the lung; however, only a few case reports of autoimmune disease complicated by pulmonary nocardiosis exist in the literature. We conducted a retrospective analysis of 24 cases of both autoimmune disease and pulmonary nocardiosis at the Peking Union Medical College Hospital between 1990 and 2012. Fifty-two cases were hospitalized with nocardiosis, 24 of whom had at least 1 autoimmune disease before the diagnosis of pulmonary nocardiosis. The cohort patients consisted of 5 men and 19 women, with a mean age of 44.2 years. All were negative for human immunodeficiency virus. All but 1 patient had received immunosuppressants, including corticosteroids, cyclophosphamide, azathioprine, methotrexate, or hydroxychloroquine. Fever (87.5%), cough (83.3%), and sputum (79.2%) were the most common clinical manifestations. Ten cases were accompanied by subcutaneous nodules and/or cutaneous abscesses, and 4 had brain abscess. Half of them were lymphocytopenic. Thirteen of the 16 cases who underwent lymphocyte subtype analysis had decreased CD4+ T-cell counts. Nineteen cases had decreased serum albumin levels. Nocardia was isolated from sputum (13/24), bronchoalveolar lavage fluid (4/6), lung tissue (5/6), pleural effusions (3/5), skin or cutaneous pus (7/10), and brain tissue (1/1). The most common imaging findings were air-space opacities (83.3%), followed by nodules (62.5%), cavitations (45.8%), and masses (37.5%). Five were administered co-trimoxazole only, and the others were treated with 2 or more antibiotics. All 5 cases with skin abscesses and 2 of the 4 cases with brain abscesses were treated by surgical incision and drainage. None underwent thoracic surgery. Corticosteroid dosages were decreased in all cases, and cytotoxic agents were discontinued in some cases. Twenty-two cases recovered, and 2 died. Pulmonary nocardiosis associated with an underlying autoimmune disease showed a female predominance and presentation at younger age. Immunosuppressant therapy, lymphocytopenia, particularly low CD4+ T-lymphocyte counts, and low serum albumin levels may be disease susceptibility factors. Air-space opacities and nodules were the most common chest imaging features, and disseminated nocardiosis with lung and skin involvement was more common among them. Early diagnosis and anti-nocardial antibiotics with modulation of the basic immunosuppressive therapy were important for them.


Statistical learning and its consequences.
Statistical learning refers to an unconscious cognitive process in which repeated patterns, or regularities, are extracted from the sensory environment. In this chapter, I describe what is currently known about statistical learning. First, I classify types of regularities that exist in the visual environment. Second, I introduce a family of experimental paradigms that have been used to study statistical learning in the laboratory. Third, I review a series of behavioral and functional neuroimaging studies that seek to uncover the underlying nature of statistical learning. Finally, I consider ways in which statistical learning may be important for perception, attention, and visual search. The goals of this chapter are thus to highlight the prevalence of regularities, to explain how they are extracted by the mind and brain, and to suggest that the resulting knowledge has widespread consequences for other aspects of cognition.


Controlled Exposure of Bioactive Growth Factor in 3D Amyloid Hydrogel for Stem Cells Differentiation.
Amyloid based hydrogels can mimic the extracellular matrix and serve as matrices for tissue engineering both in vitro and in vivo. A pH responsive self-assembled amyloid hydrogel system is used to encapsulate various growth factors for driving stem cell differentiation toward neuronal lineage. Diffusion studies with fluorescence recovery after photobleaching and bulk release with the model protein fluorescein isothiocyanate-bovine serum albumin show that encapsulated protein molecules can be released in a sustained fashion from the hydrogel over a considerable period of time (30 d). Moreover, by modulating the porosity of the hydrogel by the simple addition of salt, the encapsulated protein molecules can be retained for a longer period of time within the hydrogel. Mesenchymal stem cells, when cultured in 3D amyloid hydrogels with growth factors fibroblast growth factor 8 and sonic hedgehog, show more neuron specific differentiation as compared to hydrogel alone. This higher differentiation potential of growth factor encapsulated amyloid hydrogels can be due to concomitant exposure of cells to biomechanical as well as biochemical cues during the course of differentiation. The present study suggests that amyloid based hydrogel can be exploited for controlled growth factor delivery as well as directed stem cell differentiation to neuron.


Management of Secondary Genomic Findings.
Secondary genomic findings are increasingly being returned to individuals as opportunistic screening results. A secondary finding offers the chance to identify and mitigate disease that may otherwise be unrecognized in an individual. As a form of screening, secondary findings must be considered differently from sequencing results in a diagnostic setting. For these reasons, clinicians should employ an evaluation and long-term management strategy that accounts for both the increased disease risk associated with a secondary finding and the lower positive predictive value of a screening result compared to an indication-based testing result. Here we describe an approach to the clinical evaluation and management of an individual who presents with a secondary finding. This approach enumerates five domains of evaluation-(1) medical history, (2) physical exam, (3) family history, (4) diagnostic phenotypic testing, and (5) variant correlation-through which a clinician can distinguish a molecular finding from a clinicomolecular diagnosis of genomic disease. With this framework, both geneticists and non-geneticist clinicians can optimize their ability to detect and mitigate genomic disease while avoiding the pitfalls of overdiagnosis. Our goal with this approach is to help clinicians translate secondary findings into meaningful recognition, treatment, and prevention of disease.


Abdominal Pain in Inflammatory Bowel Disease: An Evidence-Based, Multidisciplinary Review.
Abdominal pain is one of the most common and impactful symptoms associated with inflammatory bowel disease (IBD), including both Crohn's disease and ulcerative colitis. A great deal of research has been undertaken over the past several years to improve our understanding and to optimize management of this issue. Unfortunately, there is still significant confusion about the underlying pathophysiology of abdominal pain in these conditions and the evidence underlying treatment options in this context. There is also a relative paucity of comprehensive reviews on this topic, including those that simultaneously evaluate pharmacological and nonpharmacological therapeutic options. In this review, our multidisciplinary team examines evidence for various currently available medical, surgical, and other analgesic options to manage abdominal pain in IBD.


Reflex control in heart failure: a primer for physicians.
Heart failure, cause notwithstanding, is characterized by adaptive (but harmful) increases in sympathetic activity and hormone levels, as well as by abnormal cardiovascular reflexes. Such reflex derangements may contribute to neurohumoral excitation. Consequently, normalization of the reflexes may be an important determinant of the effectiveness of therapy.


Randomized Angiographic and Intravascular Ultrasound Comparison of Dual-Antiplatelet Therapy vs Triple-Antiplatelet Therapy to Reduce Neointimal Tissue Proliferation in Diabetic Patients.
Previous studies have suggested a benefit of cilostazol in addition to standard dual-antiplatelet therapy (DAPT), reducing in-stent late luminal loss and restenosis after percutaneous coronary intervention (PCI) with bare-metal and drug-eluting stent (DES) implantation. However, there is a paucity of intravascular ultrasound (IVUS) assessment of neointimal tissue hyperplasia (NIH) after triple-antiplatelet therapy (TAPT), especially in diabetic patients treated with DES. This prospective, placebo-controlled trial was conducted in diabetic patients randomized (1:1) to receive either standard DAPT (aspirin and clopidogrel) vs TAPT with cilostazol for a minimum of 12 months after PCI with Endeavor zotarolimus-eluting stent (E-ZES). The primary endpoint was the 9-month comparison of percentage of NIH in both groups. Additionally, we compared in-stent late lumen loss, binary restenosis, major adverse cardiac event (MACE; cardiac death, non-fatal myocardial infarction, and restenosis) rates, and the incidence of vascular/bleeding complications. In total, 133 diabetic patients were enrolled (cilostazol cohort = 65 patients) with 56.4% male and mean age of 60.8 years. Overall, the two cohorts were comparable in terms of baseline clinical and angiographic characteristics, except for the reference vessel diameter, which was smaller among patients randomized to cilostazol (2.48 ± 0.46 mm vs 2.69 ± 0.48 mm; P=.01). At 9 months, there was a non-significant trend toward less percentage of NIH obstruction in the TAPT cohort (33.2 ± 8.29% vs 35.1 ± 8.45%; P=.07). However, this finding did not impact angiographic late-lumen loss (0.60 ± 0.46 mm cilostazol group vs 0.64 ± 0.48 mm control group; P=.30) and binary restenosis (9.8% vs 6.8%; P=.99). MACE rate also did not significantly differ between the cohorts (13.8% cilostazol group vs 8.8% control group; P=.81). Of note, the addition of a third antiplatelet agent did not increase vascular and bleeding complications. In diabetic patients treated with E-ZES, TAPT with cilostazol did not add any significant benefit in terms of NIH suppression or MACE reduction.


Linear IgA bullous dermatosis in a neonate.
A newborn black boy had two facial blisters at birth that progressed to bullous lesions over the trunk, genitals, extremities, and oral and tracheal mucosa. A biopsy specimen demonstrated a subepidermal bulla with mixed eosinophilic and neutrophilic, inflammatory infiltrate. Direct immunofluorescence showed linear IgA, IgG, and C3 depositions along the basement membrane zone, consistent with a diagnosis of childhood linear IgA bullous dermatosis (chronic bullous dermatosis of childhood). The skin disease was controlled with combined prednisone and dapsone. This is the youngest reported patient with the disease. Linear IgA bullous dermatosis should be considered in the differential diagnosis of blistering diseases of the newborn, and immunofluorescence should be performed on a skin biopsy specimen.


Trace metals in occupationally and nonoccupationally exposed individuals.
An epidemiological survey was conducted in Houston, Texas on five trace metals in policemen, parking garage attendants, women living near freeways and three control groups of subjects. The controls were matched with the exposed groups for covariate information such as age, sex, smoking habits, ethnic background, socioeconomic status, hair color, and education. Each subject was sampled four times for blood, urine, hair, and feces, and these samples were analyzed for lead, cadmium, zinc, manganese, and copper. Lead and cadmium were correlated with airborne exposures but zinc, manganese and copper were not. The second part of this paper deals with a market study of platinum and palladium markets and a design of an epidemiology survey of individuals occupationally and nonoccupationally exposed to these two metals. The market survey shows that although the catalytic muffler will have a major impact on the market, it is predicted that producers can meet these demands.


Favism: impairment of proteolytic systems in red blood cells.
Red blood cells (RBC) from favic patients are characterized by (a) severe oxidative damage (contributed by autoxidation of divicine and isouramil, two pyrimidine aglycones present in fava beans) and (b) greatly increased calcium levels. In vitro, both autoxidation of divicine and calcium loading produced marked alterations of proteolytic systems in intact RBC. Specifically, autoxidizing divicine inactivated procalpain, the proenzyme species of calcium-activated cytosolic neutral proteinase, or calpain. Inactivation was much greater with glucose-6-phosphate dehydrogenase (G6PD)-deficient RBC than with normal RBC. On the other hand, loading of normal and G6PD-deficient RBC with calcium resulted in conversion of procalpain to calpain and eventual autoproteolytic inactivation of calpain itself, and extensive release of acid endopeptidase activity from the membranes into the cytosol. Damaged RBC from favic patients had significantly lowered procalpain activity and an abnormal subcellular distribution of acid proteinase activity that was found mostly in the cytosol. When purified calpain was incubated with membranes from acetylphenylhydrazine (APH)-treated RBC, significant proteolysis was observed affecting mostly band 3 and hemoglobin chains, ie, the two proteins involved in the onset of aggregation of Heinz bodies. Moreover, exposure of intact RBC to 20 mmol/L APH induced depletion of procalpain activity for which the time course was inversely related to formation of Heinz bodies. These findings support the role of procalpain in protecting G6PD-deficient RBC from oxidant-induced Heinz body formation and imply that exhaustion of the procalpain-calpain system is an important step in the mechanisms of RBC damage and destruction in favism.


Dextromethorphan and memantine in painful diabetic neuropathy and postherpetic neuralgia: efficacy and dose-response trials.
There are few repeated dose-controlled trials of N-methyl-d-aspartate glutamate receptor antagonists in patients with neuropathic pain. The authors sought to evaluate two low-affinity N-methyl-d-aspartate antagonists using a novel two-stage design. The authors studied patients with painful diabetic neuropathy (DN) and postherpetic neuralgia (PHN) in two crossover trials: (1) efficacy trial (dextromethorphan vs. memantine vs. active placebo [lorazepam]) and (2) dose-response trial of the preferred active drug in responders from the first study (0% vs. 25% vs. 50% vs. 100% of each patient's maximally tolerated dose). Pain intensity was measured on a 20-point scale. Nineteen of 23 DN patients and 17 of 21 PHN patients completed the efficacy trial. Median doses for DN and PHN were 400 and 400 mg/day dextromethorphan, 55 and 35 mg/day memantine, and 1.8 and 1.2 mg/day lorazepam. In the efficacy trial, among patients with DN, dextromethorphan reduced pain intensity by a mean of 33% from baseline, memantine reduced pain intensity by a mean of 17%, and lorazepam reduced pain intensity by a mean of 16%; the proportions of subjects achieving greater than moderate pain relief were 68% with dextromethorphan, 47% with memantine, and 37% with lorazepam. Mean reductions in pain intensity in patients with PHN were 6% with dextromethorphan, 2% with memantine, and 0% with lorazepam. No comparison with placebo reached statistical significance in the efficacy trial. In the 10 DN subjects who responded to dextromethorphan, there was a significant dose-response effect on pain intensity (P = 0.035), with the highest dose significantly better than that of lorazepam (P = 0.03). Dextromethorphan is effective in a dose-related fashion in selected patients with DN. This was not true of PHN, suggesting a difference in pain mechanisms. Selective approaches to pain-relevant N-methyl-d-aspartate receptors are warranted.


Field-Tuned Superconductor-Insulator Transition with and without Current Bias.
The magnetic-field-tuned superconductor-insulator transition has been studied in ultrathin beryllium films quench condensed near 20 K. In the zero-current limit, a finite-size scaling analysis yields the scaling exponent product nuz = 1.35+/-0.10 and a critical sheet resistance, R(c), of about 1.2R(Q), with R(Q) = h/4e(2). However, in the presence of dc bias currents that are smaller than the zero-field critical currents, nuz becomes 0.75+/-0.10. This new set of exponents suggests that the field-tuned transitions with and without a dc bias current belong to different universality classes.


Cavus foot correction in adults by dorsal closing wedge osteotomy.
Twelve patients (13 feet) who underwent dorsal closing wedge osteotomy for cavus foot deformity were re-examined clinically and radiographically 46 months after surgery (range, 24 to 80 months). A dorsally based bone wedge, sized according to the deformity on the preoperative radiographs, was excised between the Lisfranc and Chopart joint lines. Eight patients (nine feet) were satisfied with the procedure. Although significant improvement of both symptoms and foot alignment was achieved, most patients continued to experience mild to moderate pain postoperatively. The outcome seems not to be directly related to the achieved surgical correction.


A brief history of Russian aphasiology.
This paper analyzes early Russian contributions to the study of aphasia, dated between 1789 and 1941. Different approaches to the problem of the organization and localization of verbal functions as well as to the understanding of mechanisms of aphasia and principles of aphasia rehabilitation are discussed. Comparisons with European and North American contributions and with contributions from later Russian writing (e.g., Luria's period) are presented to demonstrate their interconnections in shaping the course of Russian aphasiology.


Exercise training decreases the growth hormone (GH) response to acute constant-load exercise.
To assess the influence of exercise training on the growth hormone (GH) response to acute exercise, six untrained males completed a 20-min, high-intensity, constant-load exercise test prior to and after 3 and 6 wk of training (the absolute power output (PO) during each test remained constant x PO = 182.5 +/- 29.5 W). Training increased (pre- vs post-training) oxygen uptake (VO2) at lactate threshold (1.57 +/- 0.33 L.min-1 vs 1.97 +/- 0.24 L.min-1 P < or = 0.05). VO2 at 2.5 mM blood lactate concentration ([HLa]) (1.83 +/- 0.38 L.min-1 vs 2.33 +/- 0.38 L.min-1, P < or = 0.05), and VO2peak (3.15 +/- 0.54 L.min-1 vs 3.41 +/- 0.47 L.min-1, P < or = 0.05). Power output at the lactate threshold (PO-LT) increased with training from 103 +/- 28 to 132 +/- 23W (P < or = 0.05). Integrated GH concentration (20 min exercise + 45 min recovery) (microgram.L-1 x min) after 3 wk (138 +/- 106) and 6 wk (130 +/- 145) were significantly lower (P < or = 0.05) than pre-training (238 +/- 145). Plasma epinephrine and norepinephrine responses to training were similar to the GH response (EPI-pre-training = 2447 +/- 1110; week 3 = 1046 +/- 144; week 6 = 955 +/- 322 pmol.L-1; P < or = 0.05; NE pre-training = 23.0 +/- 5.2; week 3 = 13.4 +/- 4.8; week 6 = 12.1 +/- 6.8 nmol.L-1; P < or = 0.05). These data indicate that the GH and catecholamine response to a constant-load exercise stimulus are reduced within the first 3 wk of exercise training and support the hypothesis that a critical threshold of exercise intensity must be reached to stimulate GH release.