Recruitment of macrophages and polymorphonuclear leukocytes in Lyme carditis.
Lyme arthritis, caused by the spirochete Borrelia burgdorferi, can be recurrent or prolonged, whereas Lyme carditis is mostly nonrecurring. A prominent difference between arthritis and carditis is the differential representation of phagocytes in these lesions: polymorphonuclear leukocytes (PMN) are more prevalent in the joint, and macrophages predominate in the heart lesion. We have previously shown differential efficiency of B. burgdorferi clearance by PMN and macrophages, and we now investigate whether these functional differences at the cellular level may contribute to the observed differences in organ-specific pathogenesis. When we infected mice lacking the neutrophil chemokine receptor (CXCR2(-/-) mice) with spirochetes, we detected fewer PMN in joints and less-severe arthritis. Here we have investigated the effects of the absence of the macrophage chemokine receptor CCR2 on the development and resolution of Lyme carditis in resistant (C57BL/6J [B6]) and sensitive (C3H/HeJ [C3H]) strains of mice. In B6 CCR2(-/-) mice, although inflammation in hearts is mild, we detected an increased burden of B. burgdorferi compared to that in wild-type (WT) mice, suggesting reduced clearance in the absence of macrophages. In contrast, C3H CCR2(-/-) mice have severe inflammation but a decreased B. burgdorferi burden compared to that in WT C3H mice both at peak disease and during resolution. Histopathologic examination of infected hearts revealed that infected C3H CCR2(-/-) animals have an increased presence of PMN, suggesting compensatory mechanisms of B. burgdorferi clearance in the hearts of infected C3H CCR2(-/-) mice. The more efficient clearance of B. burgdorferi from hearts by CCR2(-/-) versus WT C3H mice suggests a natural defect in the recruitment or function of macrophages in C3H mice, which may contribute to the sensitivity of this strain to B. burgdorferi infection.


Purification of murine endothelial cell cultures by flow cytometry using fluorescein-labeled griffonia simplicifolia agglutinin.
Griffonia simplicifolia agglutinin (GSA) is a valuable histochemical tool in the identification of endothelium. In this study GSA labeled with fluorescein isothiocyanate (GSA-FITC) was used to purify cultures of murine cerebral microvascular endothelium. Cultures were stained with GSA-FITC, then sorted using a fluorescence-activated cell sorter (FACS). GSA-positive endothelial cells were collected, re-cultured, and subsequently re-analyzed by FACS using GSA-FITC. Cultures that initially contained 80 +/- 3 to 89 +/- 3% (X +/- SE) GSA-positive cells were purified to 98 +/- 1% positivity. Immunohistochemistry with an anti-muscle-action antibody confirmed that FACS sorting of GSA-FITC-stained cells effectively removed contaminating smooth muscle cells from endothelial cell cultures. Viability, proliferation, and prostaglandin production of the cells was unaltered by lectin staining and FACS sorting. Thus, GSA-FITC can be used in conjunction with flow cytometry to enhance the purity of murine endothelial cell cultures without adversely affecting cell viability, growth, or metabolism.


Ranitidine and single-dose antacid therapy as prophylaxis against acid aspiration syndrome in obstetric practice.
The efficacy of the non-particulate antacid 0.3 M sodium citrate in single and multiple dose regimes was investigated in 156 obstetric patients, both emergency and elective, who required operative delivery under general anaesthesia. Failure of either of these regimes to elevate the intragastric pH consistently to an acceptable level (greater than 3) led to investigation of a regime combining the histamine H2-receptor antagonist, ranitidine, and a single pre-anaesthetic dose of 0.3 M sodium citrate in a further 170 patients. Satisfactory pH values (greater than 3) were achieved in all patients studied. The results from the first 99 cases were analysed statistically by comparison with the multiple dose sodium citrate regime and showed a very significant improvement in the ranitidine group for intragastric pH and volume. No untoward side-effects were discovered in either mother or baby and the 6-hourly administration of ranitidine, which was easily complied with, had no effect on the progress of labour or operative delivery rate.


A targeted approach to sentinel lymph node biopsies in the parotid region for head and neck melanomas.
Cutaneous melanoma is on the rise in the United States, and the head and neck region is the primary site in 20% of patients. Lymph node status is the best indicator of prognosis for melanoma. In the head and neck, sentinel lymph node (SLN) biopsy presents particular challenges, with the parotid region posing difficulties that include locating the lymph nodes, less frequent visualization of blue dye, and the possibility of higher morbidity because of the proximity of lymph nodes to important neurovascular structures. Surgical approaches to the SLN dissection in the parotid region are variable, and may include superficial or total parotidectomies. Parotid-sparing SLN biopsies for head and neck melanomas were evaluated to determine rates of local recurrence. The charts of 301 patients from the Yale Melanoma Unit who underwent resection of their head and neck melanoma were reviewed. The location of the primary melanoma was noted, and the sentinel lymph node dissections from the operative reports were documented. Demographic and outcome data were recorded, including course of melanoma management, local recurrence, and postoperative course. Fifty-eight patients underwent SLN biopsy of lymph nodes in the parotid region. Parotid-sparing SLN biopsies comprised 94.8% of total surgical approaches for SLN biopsies in the parotid region. Of the remaining patients who underwent SLN biopsies in the parotid region, 5.17% had a superficial parotidectomy and none had a total parotidectomy. Sentinel lymph nodes were found in all depth layers of the parotid, and LNs were dissected out successfully without the need to remove the parotid in the most cases. The parotid region recurrence rate was 0% for SLN biopsies that either included or spared the parotid gland. There were no localized complications from the sentinel lymph node biopsies. The parotid-sparing SLN biopsy was performed without any local recurrence in the parotid region. The parotid-sparing SLN biopsy can be carried out in a safe, efficient manner without affecting the rate of local recurrence or postoperative complication. This less-invasive SLN biopsy procedure precludes the complications associated with parotidectomies and may reduce the morbidity for patients with melanomas of the head and neck.


Increased apoptosis of bone marrow CD34(+) cells and impaired function of bone marrow stromal cells in patients with systemic lupus erythematosus.
The changes in bone marrow (BM) stem cell reserve and function and stromal cell function in patients with active systemic lupus erythematosus (SLE) were investigated. The study was carried out on seven SLE patients and 28 healthy controls using flow cytometry and in vitro cell culture assays. We found that patients had low CD34(+) cells, compared with the control group, reflecting the decrease of both CD34(+)/CD38(-) and CD34(+)/CD38(+) cells. Patient CD34(+)/Fas(+) but not CD34(-)/Fas(+) cells were significantly increased. Apoptotic (7AAD(dim)) cells were higher among CD34(+)/Fas(+) than among CD34(+)/Fas(-) cells, and individual values of apoptotic CD34+ cells strongly correlated with the number of CD34(+)/Fas(+) cells. These findings are suggestive of a Fas-mediated apoptosis accounting for the low CD34(+) cells in SLE patients. Moreover, we found that patients had low numbers of granulocyte-macrophage colony-forming units (CFU-GM) and erythroid burst-forming units (BFU-E), compared with the control group, and that the generation of colony-forming cells in long-term BM cultures was significantly reduced. Patient BM stroma failed to support allogeneic progenitor cell growth. In one patient, CD34(+) cells were increased, apoptotic CD34(+)/Fas(+) cells were normalized and defective stromal cell function was restored after autologous stem cell transplantation. We concluded that defective haemopoiesis in SLE patients is probably caused, at least in part, to the presence of autoreactive lymphocytes in BM.


Design, fabrication, and performance evaluation of a concave lens array on an aspheric curved surface.
A microlens array (MLA) is a fundamental optical element, which has been widely applied in the fields of imaging sensing, 3D display, and lighting source. However, it is still a challenge to design the MLAs simultaneously satisfying small size, wide field of view, and high image quality. Herein, a novel type of concave lens array on an aspheric convex substrate (CLAACs) is presented, which is composed of an aspheric substrate and a spherical concave subeye array. The facilely designed method of the CLAACs is described and its geometric model is also established by a numerical example. Furthermore, a fabrication method, which is directly machining the CLAACs on PMMA material, is proposed. To realize the ultra-precision machining of the lens, tool path planning is carried out before fabricating. The profile, surface quality, and imaging performance of the fabricated lens are then characterized to reveal its optical capabilities. The results show that the proposed method can realize the rapid design and fabrication of lenses flexibly and efficiently. The fabricated CLAACs exhibit excellent morphology uniformity, high imaging quality, and focusing performance. The study provides a feasible solution for the design and fabrication of such lens arrays with complex discontinuous surfaces.


A new inorganic-organic hybrid material Al-SBA-15-TPI/H6P2W18O62 catalyzed one-pot, three-component synthesis of 2H-indazolo[2,1-b]phthalazine-triones.
A new inorganic-organic hybrid material Al-SBA-15-TPI/H6P2W18O62 was prepared and fully characterized by SEM, XRD, FT-IR, TGA-DTA, and UV-Vis spectroscopic techniques. Then, the prepared nanomaterial was used as a simple, cost-effective, and reusable heterogeneous catalyst for the synthesis of 2H-indazolo[2,1-b]phthalazine-1,6,11(13H)-trione derivatives by a one-pot, three-component condensation reaction of phthalhydrazide, cyclic diones, and aromatic aldehydes under solvent free conditions at 100 °C in a short time. This methodology has proven to be efficient and environmentally benign in terms of high yields and low reaction times and offers significant improvements with regard to the scope of transformation and simplicity of operation by avoiding expensive or corrosive catalysts.


Evaluation of human resistin assays with serum from patients with type 2 diabetes and different degrees of insulin resistance.
Resistin is a peptide hormone encoded at the RSTN gene that since its detection in mice is considered to be an important link between obesity and insulin resistance. However, the study reports and especially the human data are contradictory and require further investigation. The purpose of this study was to evaluate three commercially available resistin ELISAs with different target epitopes (Phoenix, Belmont, CA, USA (PH); Biovendor, Brno, Czech Republic (BV); and Immundiagnostik, Bensheim, Germany (ID)) from a laboratory and clinical perspective. All three assays successfully passed the standardized technical validation procedure, with an inter- and intra-assay variability below 10% and 15%, respectively. They proved to be different with regard to calibration and reference ranges, which may be linked to the different antibody specificities. The clinical evaluation was performed with fasting serum samples from 78 patients with type 2 diabetes (43 female, 35 male, age (mean +/- SD, range): 67 +/- 10, (41-86) years; BMI: 29.2 +/- 4.2 (21.6-41.9) kg/m2). Insulin resistance was calculated from the fasting insulin and glucose values by means of the HOMA analysis. Intact proinsulin served as comparative laboratory marker for insulin resistance. The mean resistin values of patients without insulin resistance were slightly higher (PH: 9.5 +/- 2.8 ng/ml; BV: 4.1 +/- 4.0 ng/ml; ID: 3.8 +/- 9.0 ng/ml) than the mean values of the resistant patients (PH: 9.0 +/- 1.7 ng/ml, n.s.; BV: 3.8 +/- 1.3 ng/ml, n.s.; ID: 0.8 +/- 1.0 ng/ml, p<0.05). Intact proinsulin levels correlated well with the HOMA score values (r = 0.64, p<0.001). No correlation was seen between any of the resistin assays and any of the other clinical or laboratory observation parameters collected, such as BMI, age, disease duration, triglycerides, LDL, HDL, insulin, glucose, or intact proinsulin. In conclusion, the resistin assays showed good technical quality, but the diagnostic value remains still unclear. It may, however, be concluded from this study that at least in cross-sectional epidemiological investigations, fasting human resistin concentrations are not significantly correlating with any clinical measure for insulin resistance.


Posterolateral surface electrical stimulation of abdominal expiratory muscles to enhance cough in spinal cord injury.
Spinal cord injury (SCI) patients have respiratory complications because of abdominal muscle weakness and paralysis, which impair the ability to cough. This study aims to enhance cough in high-level SCI subjects (n = 11, SCI at or above T6) using surface electrical stimulation of the abdominal muscles via 2 pairs of posterolaterally placed electrodes. From total lung capacity, subjects performed maximum expiratory pressure (MEP) efforts against a closed airway and voluntary cough efforts. Both efforts were performed with and without superimposed trains of electrical stimulation (50 Hz, 1 second) at a submaximal intensity set to evoke a gastric pressure (P(ga)) of 40 cm H(2)O at functional residual capacity. In the MEP effort, stimulation increased the maximal P(ga) (from 21.4 ± 7.0 to 59.0 ± 5.7 cm H(2)O) and esophageal pressure (P(es); 47.2 ± 11.7 to 65.6 ± 13.6 cm H(2)O). During the cough efforts, stimulation increased P(ga) (19.5 ± 6.0 to 57.9 ± 7.0 cm H(2)O) and P(es) (31.2 ± 8.7 to 56.6 ± 10.5 cm H(2)O). The increased expiratory pressures during cough efforts with stimulation increased peak expiratory flow (PEF, by 36% ± 5%), mean expiratory flow (by 80% ± 8%), and expired lung volume (by 41% ± 16%). In every subject, superimposed electrical stimulation improved peak expiratory flow during cough efforts (by 0.99 ± 0.12 L/s; range, 0.41-1.80 L/s). Wearing an abdominal binder did not improve stimulated cough flows or pressures. The increases in P(ga) and PEF with electrical stimulation using the novel posterolateral electrode placement are 2 to 3 times greater than improvements reported in other studies. This suggests that posterolateral electrical stimulation of abdominal muscles is a simple noninvasive way to enhance cough in individuals with SCI.


Incidence and risk factors of embolized particles in carotid artery stenting and association with clinical outcome.
One of the mechanisms for periprocedural neurologic events in carotid artery stenting (CAS) is catheter manipulation within the aorta and supraaortic arteries causing plaque embolization. Therefore, the present analysis sought to determine risk factors for embolic particle dimensions and their relationship with adverse clinical events after CAS. Between 1999 and 2015 embolic protection devices (EPD) of a total of 944 CAS procedures were evaluated regarding the occurrence and size of captured particles. Particles were found in 819 of 944 (87%) EPDs. Larger particles were detected in procedures using open cell stents (150±282μm vs. 107±177μm; p=0.005) and longer stents (≥40mm) (165±315μm vs. 122±215μm; p=0.026). With increasing learning curve, particle size was continually reduced (168±282μm in the first third of the cohort vs. 127±309μm in the second third vs. 108±114μm in the last third; p=0.009). Longer stents and use of Acculink stent were found to be independent predictors for particle diameter. In patients who died or sustained a stroke during long-term follow-up (median 5.5years [IQR 2.6-7.9]) significantly larger particles were captured during CAS compared to those patients with an uneventful follow-up (160±330μm vs. 121±195μm; p=0.047). In the vast majority of CAS procedures particles could be retrieved from the EPDs used. Procedural characteristics such as stent type and stent length were associated with larger particles.


[Surgical therapy of rectal prolapse. Our clinical experience of 12 years of observations].
AA. are reporting their experience on the subject of the surgical treatment of the rectal prolapse in all his clinical forms, during 12 years of activity that has taken place in the clinical surgery of the University of Ferrara. From their casuistry it is shown that usually this pathology is joined with other morbid forms of the small pelvis which vary according to the degree of the prolapse. They emphasize the excellent results obtained and support the surgical way of laparotomy adopted in the treatment of prolapse of II type (incomplete) and III type (complete).


Progression-free survival in advanced ovarian cancer: a Canadian review and expert panel perspective.
Ovarian cancer is leading cause of gynecologic cancer mortality in Canada. To date, overall survival (os) has been the most-used endpoint in oncology trials because of its relevance and objectivity. However, as a result of various factors, including the pattern of sequential salvage therapies, measurement of os and collection of os data are becoming particularly challenging. Phase ii and iii trials have therefore adopted progression-free survival (pfs) as a more convenient surrogate endpoint; however, the clinical significance of pfs remains unclear. This position paper presents discussion topics and findings from a pan-Canadian meeting of experts that set out to evaluate the relevance of pfs as a valid endpoint in ovarian cancer;reach a Canadian consensus on the relevance of pfs in ovarian cancer; andtry to address how pfs translates into clinical benefit in ovarian cancer.Overall, the findings and the group consensus posit that future studies should ensure that trials are designed to evaluate pfs, os, and other clinically relevant endpoints such as disease-related symptoms or quality of life;incorporate interim futility analyses intended to stop accrual early when the experimental regimen is not active;stop trials early to declare superiority only when compelling evidence suggests that a new treatment provides benefit for a pre-specified, clinically relevant endpoint such as os or symptom relief; anddiscourage early release of secondary endpoint results when such a release might increase the frequency of crossover to the experimental intervention.


Gender and the integration of acoustic dimensions of prosody: implications for clinical studies.
This study was conducted to detect the existence of a relationship between spectral and temporal prosodic cues and to examine gender differences in any such relationship. The rationale for the investigation was to gain a greater understanding of normal prosody and the requirements for control groups in clinical studies of prosody. Ten male and 10 female speakers with no known speech or neurological deficits participated in the study. They performed a reading task which involved delivering 10 sentences first with a declarative and then repeated with an interrogative intonation (20 sentences per speaker). Intrasubject and intersubject analyses of the speech data revealed a dependence of pitch on duration that differed between male and female speakers. Significant differences between the genders were also found in speech rate, pitch range, and pitch slope. The findings suggest that an integrated treatment of acoustic cues may provide a more invariant feature of normal prosody against which clinical groups may be compared. The data also imply that in clinical studies of the production of prosody gender should be carefully controlled.


Interferon-γ and its pathway-associated gene expression in the vaginal tissue of premenopausal females with pelvic organ prolapse.
Interferon (IFN)-γ is a potent proinflammatory molecule. However, few studies have investigated the expression levels of IFN-γ during pelvic organ prolapse (POP). In the present study, the expression levels and tissue localization of IFN-γ and its pathway-associated genes were detected in the vaginal walls of premenopausal females with POP and asymptomatic controls using quantitative polymerase chain reaction and immunohistochemistry. When compared with the matched controls, an 8.6-fold increase in IFN-γ, 3.8-fold increase in IFN-γ receptor (IFNGR)1, 2.6-fold increase in IFNGR2, 3.4-fold increase in signal transducer and activator of transcription-1, 2.2-fold increase in janus kinase-1 and 5.1-fold increase in nuclear factor (NF)-κB mRNA expression levels were observed in the females with premenopausal POP. In all the females with POP, higher mRNA expression levels of IFN-γ and its receptors were observed when compared with the controls. Expression levels of all the proteins were detected by immunohistochemistry, and the results demonstrated higher staining for IFN-γ, IFNGRs and pathway-associated genes in females with POP. Therefore, the results indicated that IFN-γ may be used as an inflammatory marker for POP development, and is associated with NF-κB.


Polyphosphazenes enable durable, hemocompatible, highly efficient antibacterial coatings.
Biocompatible antibacterial coatings are highly desirable to prevent bacterial colonization on a wide range of medical devices from hip implants to skin grafts. Traditional polyelectrolytes are unable to directly form coatings with cationic antibiotics at neutral pH and suffer from high degrees of antibiotic release upon exposure to physiological concentrations of salt. Here, novel inorganic-organic hybrid polymer coatings based on direct layer-by-layer assembly of anionic polyphosphazenes (PPzs) of various degrees of fluorination with cationic antibiotics (polymyxin B, colistin, gentamicin, and neomycin) are reported. The coatings displayed low levels of antibiotic release upon exposure to salt and pH-triggered response of controlled doses of antibiotics. Importantly, coatings remained highly surface active against Escherichia coli and Staphylococcus aureus, even after 30 days of pre-exposure to physiological conditions (bacteria-free) or after repeated bacterial challenge. Moreover, coatings displayed low (<1%) hemolytic activity for both rabbit and porcine blood. Coatings deposited on either hard (Si wafers) or soft (electrospun fiber matrices) materials were non-toxic towards fibroblasts (NIH/3T3) and displayed controllable fibroblast adhesion via PPz fluorination degree. Finally, coatings showed excellent antibacterial activity in ex vivo pig skin studies. Taken together, these results suggest a new avenue to form highly tunable, biocompatible polymer coatings for medical device surfaces.


Predictors of Intelligence after Temporal Lobectomy in Children with Epilepsy.
Performance on standardized measures of intelligence was examined before and after temporal lobectomy in 50 children and adolescents. Group results showed small positive changes in Performance IQ (PIQ), but not Verbal IQ (VIQ). Analyses of individual patients showed that 28% had a significant change in VIQ after surgery, half of whom showed improvements. Increases in VIQ were associated with older age at time of surgery, lower VIQ before surgery, and positive seizure outcome after surgery, whereas longer follow-up time was predictive of smaller change. Increases in PIQ were seen in 25% of patients, and decreases occurred in 8%. Predictors of postoperative change in PIQ were dual pathology and longer follow-up interval, both of which showed negative correlations. Enhanced intellectual function is not one of the benefits to be expected in the majority of children undergoing temporal lobectomy. Further studies are required to determine whether these conclusions may or may not be applied to other aspects of cognitive function.


Outcome of Patients With Breast Cancer Treated in a Private Health Care Institution in Brazil.
Middle-income countries like Brazil often have a dichotomous health care system in which patients may be treated in either public or private institutions that differ substantially in terms of level of access to diagnostic and therapeutic procedures. This was a prospective, observational study to assess real-world data in 1,230 female patients with breast cancer who were treated in a private health care institution between 2012 and 2016 in Brazil. Breast cancer in these patients mostly was diagnosed at early (79.0% stages I or II) or locally advanced (16.1% stage III) stages. The primary tumor was resected in 89.0% of cases, most often through breast-conserving surgery (55.1%). Patients with locally advanced disease received more aggressive therapy (eg, higher rates of mastectomy, axillary dissection and chemotherapy use) than patients with early-stage disease. The estimated 2-year overall survival (OS) was 95.3%. Survival was significantly longer among patients with stage I or II disease (2-year OS, 97.9% and 97.5%, respectively) than those with stage III or IV disease (89.4% and 69.5%, respectively; P < .01). Tumor grade was also correlated with OS in the overall cohort ( P = .05); triple-negative status was only prognostic for patients with stage III disease ( P < .01). The data provided aid understanding of the current scenario of breast cancer presentation and treatment in the Brazilian private health care system and may serve as a foundation to guide resource allocation. Our results reinforce the need to pursue adequate access to cancer care in low- and middle-income countries to optimize patient outcome.


Analysis of 75 cases of acute myeloid leukaemia classified according to the FAB classification.
75 cases of acute myeloid leukaemia were retrospectively classified according to the French-American-British (FAB) classification. It was found that: (1) the proposed classification was easily applicable and reproducible; (2) M2 subtype was the most frequent (48%); (3) splenomegaly was absent in M1 subtype, and (4) in M2 subtype, a considerable number of cases presented with normal neutrophil and platelet counts.


Leaving No Stone Unturned: Factors Associated With Overturning Insurance Claim Denials for Urological Conditions in New York State.
Denied health claims in New York State may be appealed by external review. After appeal, the denial can either be upheld or overturned. Regardless, an appeal process results in delays in care and can negatively impact patient health and practice efficiency. This study aimed to describe the epidemiology of New York State urological external appeals and assess factors associated with successful appeals. The New York State External Appeals database was queried for 2019-2021 urological cases (N=408). Patient age, gender, decision year, appeal reason, diagnosis, treatment, and reference to American Urological Association were extracted. Annual appeal volume was analyzed by linear regression. Relationships between appeal outcomes and characteristics were analyzed by χ2 tests. Multivariate logistic regression analysis was used to identify factors related to overturns. Overall, 39.5% of denials in this data set were overturned. Appeal volume increased annually, with overturned cases increasing 244% (mean 29.5, P = .068). Of reviewers, 15.6% referenced American Urological Association guidelines in their decision. Appeals mostly involved ages 40-59 years (32.4%), inpatient stays (63.5%), and infections (32.4%). Female sex, age 80+, diagnosis of incontinence/lower urinary tract symptoms, treatment with home health care, medications, or surgical services, and not referencing American Urological Association guidelines were significantly associated with successful appeal. Referencing American Urological Association guidelines had 70% decreased odds of overturning denials. Our findings suggest that upon appeal of denied claims, practices may have a high chance of overturning an initial denial and this trend is rising. These findings will help serve as a reference for future external appeals research and urology policy and advocacy groups.


Remigration of migrants with severe disease: myth or reality?--a register-based cohort study.
'Remigration bias' is often referred to when explaining low mortality outcomes among migrants compared with local-born. The hypothesis suggests that severely ill migrants tend to return to their country of origin, but it has hitherto not been tested in a large-scale epidemiological study. Consequently, we studied whether migrants with severe disease were more likely to emigrate compared with migrants without severe disease. A historic prospective cohort study was conducted based on all adult refugees and family reunification immigrants (n = 114,331) who obtained residence permission in Denmark between 1 January 1993 and 31 December 2010. Migrants with severe disease were identified through the Danish National Patient Register. Emigrations during follow-up (1 January 1993 to 31 December 2011) were identified using the Danish Civil Registration System. Hazard ratios were calculated for emigration among migrants with different levels of disease severity, adjusting for sex, age and income. Results showed progressively fewer emigrations with increasing disease severity. Migrants with low (HR = 0.92; 95% CI: 0.80-1.06), moderate (HR = 0.84; 95% CI: 0.67-1.06) and high (HR = 0.70; 95% CI: 0.55-0.90) disease severity had fewer emigrations to 'country of origin' compared with migrants without disease. For emigration to 'any country', results likewise showed fewer emigrations among migrants with low (HR = 0.86; 95% CI: 0.78-0.95), moderate (HR = 0.73; 95% CI: 0.62-0.87) and high (HR = 0.64; 95% CI: 0.53-0.76) disease severity. This tendency was also observed by nationality and migrant status. On the disease-specific level, no uniform tendencies in emigration patterns were identified. The results do not generally support the hypothesis of 'remigration bias' but rather suggest the opposite. Accordingly, remigration bias does not appear to explain lower mortality of migrants.


Early Secure Attachment as a Protective Factor Against Later Cognitive Decline and Dementia.
The etiology of neurodegenerative disorders such as dementia is complex and incompletely understood. Interest in a developmental perspective to these pathologies is gaining momentum. An early supportive social environment seems to have important implications for social, affective and cognitive abilities across the lifespan. Attachment theory may help to explain the link between these early experiences and later outcomes. This theory considers early interactions between an infant and its caregiver to be crucial to shaping social behavior and emotion regulation strategies throughout adult life. Furthermore, research has demonstrated that such early attachment experiences can, potentially through epigenetic mechanisms, have profound neurobiological and cognitive consequences. Here we discuss how early attachment might influence the development of affective, cognitive, and neurobiological resources that could protect against cognitive decline and dementia. We argue that social relations, both early and late in life, are vital to ensuring cognitive and neurobiological health. The concepts of brain and cognitive reserve are crucial to understanding how environmental factors may impact cognitive decline. We examine the role that attachment might play in fostering brain and cognitive reserve in old age. Finally, we put forward the concept of affective reserve, to more directly frame the socio-affective consequences of early attachment as protectors against cognitive decline. We thereby aim to highlight that, in the study of aging, cognitive decline and dementia, it is crucial to consider the role of affective and social factors such as attachment.


Continuous glucose monitoring: coming of age?
In a recent issue of the Journal of Clinical Endocrinology and Metabolism, an Endocrine Society Clinical Practice Guideline on Continuous Glucose Monitoring (CGM) was published, co-sponsored by the European Society of Endocrinology. Such a guideline is a necessary step in the maturation of any new technology. This commentary tries to delineate where we stand some 10 years after the first retrospective CGM device entered the market from a European perspective.


Assessment of M2/ANXA5 haplotype as a risk factor in couples with placenta-mediated pregnancy complications.
The aim of this study was to confirm the associated M2/ANXA5 carrier risk in women with placenta-mediated pregnancy complications (PMPC) and to test their male partners for such association. Further analysis evaluated the influence of maternal vs. paternal M2 alleles on miscarriage. Two hundred eighty-eight couples with preeclampsia (PE), intrauterine growth restriction (IUGR), or premature birth (PB) were recruited (n = 96 of each phenotype). The prevalence of the M2 haplotype was compared to two control cohorts. They included a group of women with a history of normal pregnancy without gestational pathology (Munich controls, n = 94) and a random population sample (PopGen controls, n = 533). Significant association of M2 haplotype and pregnancy complications was confirmed for women and for couples, where prevalence was elevated from 15.4 to 23.8% (p < 0.001). Post hoc analyses demonstrated an association for IUGR and PB individually. A strong link between previous miscarriages and M2 carrier status was identified which may explain the predisposition to placental pregnancy complication. M2/ANXA5 appears to be a risk factor for adverse pregnancy outcomes related, but not limited to miscarriages, with similar prevalence in women and their male partners. These findings support the proposed physiological function of ANXA5 as an embryonic anticoagulant that appears deficient in contiguous specter of thrombophilia-related pregnancy complications culminating more frequently in miscarriage in a maternal M2 carrier background.


Optimization of Coconut Fiber in Coconut Shell Concrete and Its Mechanical and Bond Properties.
Coconut shell concrete is one of the recently established lightweight concretes. This paper discusses the optimization of adding coconut fibers in both coconut shell concrete and conventional concrete. Coconut fibers at different aspect ratios of 16.67, 33.33, 50, 66.67, 83.33, and 100 and volume fractions of 1, 2, 3, 4, and 5% were tried. The maximum compressive strength was attained at an aspect ratio of 83.33 and volume fraction of 3% for conventional concrete, and aspect ratio 66.67 and volume fraction 3% for coconut shell concrete. Flexural strength increased by 30.63% (conventional concrete) and 53.66% (coconut shell concrete) on the addition of coconut fibers. Similarly, the split tensile strength increased by 19.44% and 30%, respectively. The number of blows needed for failure of specimen in impact resistance test was more for concrete mixed with fibers. The experimental bond stresses were higher than the theoretical values recommended by IS 456: 2000 (Indian Standard) and BS 8110 (British Standard). This study shows that the addition of coconut fiber enhances the properties of both conventional and coconut shell concrete.


Recent Issues in Medical Journal Publishing and Editing Policies: Adoption of Artificial Intelligence, Preprints, Open Peer Review, Model Text Recycling Policies, Best Practice in Scholarly Publishing 4th Version, and Country Names in Titles.
In Korea, many editors of medical journal are also publishers; therefore, they need to not only manage peer review, but also understand current trends and policies in journal publishing and editing. This article aims to highlight some of these policies with examples. First, the use of artificial intelligence tools in journal publishing has increased, including for manuscript editing and plagiarism detection. Second, preprint publications, which have not been peer-reviewed, are becoming more common. During the COVID-19 pandemic, medical journals have been more willing to accept preprints to adjust rapidly changing pandemic health issues, leading to a significant increase in their use. Third, open peer review with reviewer comments is becoming more widespread, including the mandatory publication of peer-reviewed manuscripts with comments. Fourth, model text recycling policies provide guidelines for researchers and editors on how to appropriately recycle text, for example, in the background section of the Introduction or the Methods section. Fifth, journals should take into account the recently updated 4th version of the Principles of Transparency and Best Practice in Scholarly Publishing, released in 2022. This version includes more detailed guidelines on journal websites, peer review processes, advisory boards, and author fees. Finally, it recommends that titles of human studies include country names to clarify the cultural context of the research. Each editor must decide whether to adopt these six policies for their journals. Editor-publishers of society journals are encouraged to familiarize themselves with these policies so that they can implement them in their journals as appropriate.


Archaeopteryx is not a forgery.
Archaeopteryx lithographica might be regarded as the most important zoological species known, fossil or recent. Its importance lies not in that its transitional nature is unique-there are many such transitional forms at all taxonomic levels-but in the fact that it is an obvious and comprehensible example of organic evolution. There have been recent allegations that the feather impressions on Archaeopteryx are a forgery. In this report, proof of authenticity is provided by exactly matching hairline cracks and dendrites on the feathered areas of the opposing slabs, which show the absence of the artificial cement layer into which modern feathers could have been pressed by a forger.


Stability of binary mixtures in electric field gradients.
We consider the influence of electric field gradients on the phase behavior of nonpolar binary mixtures. Small fields give rise to smooth composition profiles, whereas large enough fields lead to a phase-separation transition. The critical field for demixing as well as the equilibrium phase-separation interface are given as a function of the various system parameters. We show how the phase diagram in the temperature-composition plane is affected by electric fields, assuming a linear or nonlinear constitutive relations for the dielectric constant. Finally, we discuss the unusual case where the interface appears far from any bounding surface.


[Chemical studies on the constituents of Daphne koreane Nakai].
In this paper three compounds isolated from Daphne koreane are described. Their structures have been identified as beta-sitosterol, naringenin and 7,8-dimethoxycoumarin on the basis of spectral data and chemical reactions.


Cognitive representations of handball tactic actions in athletes-The function of expertise and age.
The tactical cooperation for the optimal interaction of team members is an essential performance-determining variable in sports games. The underlying cognitive memory structures of cooperative tactical actions have so far been little researched. Therefore, this study investigated the cognitive memory structure of tactical knowledge of handball actions in teams of different expertise and age groups. In the first experiment, tactical mental representation structures (TMRS) of 30 adult handball players of two different level of expertise were investigated. In the second experiment, TMRS of 57 youth handball players from three age levels were investigated. In both experiments the TMRS was measured with the structure dimensional analysis of mental representation (SDA-M) method. The SDA-M commences with a splitting procedure of a given set of concepts and reveals with a cluster analysis the relational structures of the concepts on an individual and a group level. Experiment one revealed that the TMRS differed significantly between skilled either/or less experienced handball players. Skilled handball players showed a hierarchical organized representation that shared more features with the basic tactical structure of the handball game than less experienced players. The second experiment revealed age-related differences of the TMRS between the age groups of the U15, U17 and U19 teams. Further data analysis revealed significant differences of the TMRS between experienced and less experienced handball players and between local and regional competition level players. We conclude that our current findings suggest that tactical expertise is mediated by elaborate cognitive tactical knowledge in memory. Furthermore, our results indicate that tactical knowledge plays a substantial role during tactical skill learning as it differs as function of age, experience, and competition level. From this point of view, team representations of game situations can be seen as a crucial factor for efficient and common interaction in fast-paced team sports.


[Left Ventricular Assist Device Therapy - Ways to Improve the Ambulatory Care].
The use of left-ventricular assist device therapy (LVAD) in terminal heart failure patients is increasing. Many patients are receiving LVAD-therapy as final solution (destination therapy). After discharge from the implanting heart center patient-centered care has to be implemented on an outpatient basis. A responsible ambulatory treatment of this severe heart failure population requires knowledge about LVAD specific problems (general medical care, long term complications, device management). The referring cardiologist as well as the private practitioner should be more involved in the care of patients with LVAD. By this means patients safety would increase and the overall costs decline not at least due to fewer hospital readmissions.


Monosodium urate crystals induce extracellular DNA traps in neutrophils, eosinophils, and basophils but not in mononuclear cells.
Neutrophil extracellular traps (NETs) are fibers of extracellular DNA released from neutrophils due to overwhelming phagocytic stimuli. The function of NETs is to trap and kill microbes to avoid spreading of potential pathogens. NETs are formed after encounter with various gram-positive and -negative bacteria but also in response to mediators causing sterile inflammation like interleukin-8 (IL-8), tumor necrosis factor (TNF), and phorbol myristate acetate (PMA). Here we show the formation of NETs (NETting) in response to monosodium urate (MSU) crystals as further model for sterile inflammation. We identified monocytes, neutrophils, and eosinophils as MSU phagocytosing cells. Basophils did not take up the crystals, instead they upregulated their activation marker CD203c after contact with MSU. Nevertheless, MSU crystals induced extracellular trap formation also in basophils, like in eosinophils and neutrophils, which phagocytose the crystals. In contrast, monocytes do not form NETs despite uptake of the MSU crystals. In contrast to the canonical stimuli like bacteria and PMA, MSU-induced NETosis was not abrogated by plasma. Our data show that MSU crystals induce extracellular DNA trap formation in all three granulocytes lineages (NETs, EETs, and BETs) but not in monocytes, and DNA externalization does not necessitate the uptake of the crystals.


A cross-sectional study exploring cognitive impairment in kidney failure.
Little is known of the prevalence or associated factors of cognitive impairment in people with kidney failure. Assessment of cognition is necessary to inform comprehension of healthcare information, aptitude for dialysis modality and informed decision making. This study sought to determine the prevalence and factors associated with cognitive impairment in people with kidney failure. Prospective cross-sectional. Participants (n = 222) with chronic kidney disease grade 5 (CKD G5) including those not treated with dialysis, those undertaking dialysis independently or in a facility (CKD 5D), and those with a kidney transplant (CKD 5T). Data were collected using the Montreal Cognitive Assessment tool, the Hospital Anxiety and Depression Scale (only the depression subscale), and a demographic questionnaire. Type of kidney disease and comorbidities were extracted from participants' hospital records. Participants were 61 ± 13.63 years old; most were male (61.26%), and diabetes was the primary cause of kidney disease (34%). Prevalence of cognitive impairment was 34% although it was significantly higher for those in CKD G5 compared with other groups. A number of factors were found to be associated with cognitive impairment including, age, diabetes, hypertension, education, haemoglobin, albumin, parathyroid hormone, CKD G5, and length of time on treatment. Cognitive impairment in kidney failure is common and it has significant implications for informed decision making and treatment choices. Routine assessment of cognitive function is an important part of clinical practice.


The art of common ground: emergence of a complex pragmatic language skill in adolescents with autism spectrum disorders.
Deficits in pragmatic language are central to autism spectrum disorder (ASD). Here we investigate common ground, a pragmatic language skill in which speakers adjust the contents of their speech based on their interlocutor's perceived knowledge, in adolescents with ASD and typical development (TD), using an experimental narrative paradigm. Consistent with prior research, TD participants produced shorter narrations when they shared knowledge with an interlocutor, an effect not observed at the group level in ASD. This effect was unrelated to general skills such as IQ or receptive vocabulary. In ASD, the effect was correlated with age and symptom severity: older and less severely affected participants did shorten their narratives. Several metrics (including explicit references to common ground, speech disfluencies, and communicative quality ratings) suggested that, although adolescents with ASD did not show implicit reductions in their narrative length, they were aware of common ground, and communicated differently in its presence.


Once-daily topical brimonidine tartrate gel 0·5% is a novel treatment for moderate to severe facial erythema of rosacea: results of two multicentre, randomized and vehicle-controlled studies.
Erythema of rosacea is thought to result from abnormal cutaneous vasomotor activity. Brimonidine tartrate (BT) is a highly selective α(2) -adrenergic receptor agonist with vasoconstrictive activity. To determine the optimal concentration and dose regimen of topical BT gel for the treatment of erythema of rosacea and to evaluate its efficacy and safety. In study A, 122 subjects were randomized to receive a single application of BT 0·07%, 0·18%, 0·5% or vehicle. In study B (4-week treatment and 4-week follow-up), 269 subjects were randomized to receive BT 0·5% once daily, BT 0·18% once daily, vehicle once daily, BT 0·18% twice daily or vehicle twice daily. Evaluations included Clinician's Erythema Assessment (CEA), Patient's Self-Assessment (PSA), Chroma Meter measurements and adverse events. In study A, a single application of topical BT gel reduced facial erythema in a dose-dependent fashion. A significant difference between BT 0·5% and vehicle in Chroma Meter redness value was observed from 30min to 12h after application. In study B, BT 0·5% once daily had a statistically superior success profile (defined as a two-grade improvement on both CEA and PSA over 12h) compared with vehicle once daily on days 1, 15 and 29 (all P<0·001). No tachyphylaxis, rebound of erythema or aggravation of other disease signs (telangiectasia, inflammatory lesions) was observed. All regimens were safe and well tolerated with similarly low incidence of adverse events. Once-daily BT gel 0·5% is well tolerated and provides significantly greater efficacy than vehicle gel for the treatment of moderate to severe erythema of rosacea.


Microsomal effects of cyproterone acetate and flutamide in rat testis.
1. Effects of two doses of cyproterone acetate (CA) and flutamide (FLU) (50 and 100 mg/kg/3 days) on the testicular steroidogenesis in male rats have been investigated, by measuring the content of cytochrome P-450, cytochrome b5 and cytochrome c reductase activity in the microsomal fraction. 2. CA provoked a significant decrease in cytochrome P-450 content while FLU induced an increase with the lowest dose but a significant decrease after administration of 100 mg/kg. 3. On the other hand, in all cases the cytochrome b5 and cytochrome c reductase activity remained unchanged. 4. The plasma levels of LH and testosterone were measured after CA and FLU injection (50 and 100 mg/kg/3 days). 5. CA administration provoked a reduction in blood levels of these hormones while FLU induced a significant increase in both. 6. These data suggested that CA and FLU modified the cytochrome P-450 in rat testes by an indirect mechanism, probably through the modification of LH plasma levels.


Modeling and optimization of phenylalanine ammonia lyase stabilization in recombinant Escherichia coli for the continuous synthesis of l-phenylalanine on the statistical-based experimental designs.
Some approaches for improving recombinant phenylalanine ammonia lyase (PAL) stability in Escherichia coli during the enzymatic methods of l-phenylalanine (l-Phe) production were developed following preliminary studies by means of statistical-based experiment designs (response surface method). The traditional non-statistical technology was used to screen four critical factors for PAL stability during the bioconversion process, viz., glycerin, sucrose, 1,4-dithiothreitol (DTT), and MgSO(4). The central composite design (CCD) was applied to optimize the combined effect of critical factors for recombinant PAL stability and understand the relationship between the factors and PAL stability. The optimum values for testing variables were 13.04 mM glycerin, 1.87 mM sucrose, 4.09 mM DTT, and 69 mM Mg(2+). A second-order model equation was suggested and then validated experimentally. The model adequacy was very satisfactory because the coefficient of determination was 0.88. The maximum PAL activity was retained as 67.73 units/g after three successive cycles of bioconversion. In comparison to initial PAL activity, the loss of PAL activity was only 22%. PAL activity was enhanced about 23% in comparison to the control (without any stabilizer additives). PAL stability was significantly improved during successive bioconversion. The results obtained here verified the effectiveness of the applied methodology and may be helpful for l-Phe production on an industrial scale.


Student pharmacist perspectives on providing pharmacy-access hormonal contraception services.
To assess student pharmacists' interest and opinions in providing reproductive health services, particularly hormonal contraception (HC), in their future practices. This descriptive, nonexperimental, cross-sectional study was conducted in California between February and May 2007. Surveys were distributed to 790 second- and third-year student pharmacists to measure interest, opinions, and perceived barriers in providing HC services. 502 survey responses (63.5% response rate) were received. Student pharmacists reported interest in providing HC services (96.2%) to both minors and adults (53.3%), adults (40.6%), or minors (6.2%). Students felt that patients would benefit from improved access and advice (94.0%). Inadequate pharmacist time was deemed an extremely important barrier in determining whether pharmacists could efficiently and effectively provide HC services, followed by lack of private counseling area in the pharmacy, inadequate patient health information, and lack of appropriate incentive structure. Students were interested in providing other reproductive health services, specifically preventive measures against sexually transmitted infections (STIs; 89.2%) and STI treatment for the partners of patients presenting with valid STI prescriptions (88.4%). Student pharmacists were very interested in providing pharmacy access to HC and related reproductive health services as future practitioners. The willingness of student pharmacists to provide this support indicates that pharmacy access to HC could be a viable service.


Plastic properties of gold surfaces nanopatterned by ion beam sputtering.
We review the mechanical properties of defective roughened surfaces with the major emphasis on nanoindentation work. We also report novel results in which force versus penetration curves and AFM images of the nanoindented surface are compared for a flat surface of Au(001) and an Ar(+) bombarded one, both with a high and a low flux of ions. We have found that bombarded surfaces yield at a lower stress than untreated flat ones. Surfaces bombarded at high flux show a large roughness and their yield point, marking the onset of surface plasticity, decreases with respect to that of the flat surface or of the surface bombarded with a low flux. The present results are compared with earlier work on nanoindented vicinal surfaces in which the sole surface modifications with respect to the flat surface were the presence of a high density of steps. It is concluded that a softening effect due to the bombardment-induced nanostructure of the surface dominates over the hardening one due to defect creation and interaction in the surface neighbourhood.


Economies of scale in the production of public health services: an analysis of local health districts in Florida.
We examined the existence and the extent of scale and scope economies in the delivery of public health services. We also tested the strength of agency, population, and community characteristics that moderate scale and scope economies. We collected service count and cost data for all Florida local health districts for 2008 and 2010, complemented with data on agency, population, and community characteristics. Using translog cost functions, we built models of operating efficiencies for 5 core public health activities: communicable disease surveillance, chronic disease prevention, food hygiene, on-site sewage treatment, and vital records. Economies of scale were found in most activities, with cost per unit decreasing as volume increased. The models did not, however, identify meaningful economies of scope. Consolidation or regionalization might lower cost per unit for select public health activities. This could free up resources for use in other areas, further improving the public's health.


Determinants of First-Time Cancer Examinations in a Rural Community: A Mechanism for Behavior Change.
After conducting a media campaign focusing on the importance of oral and pharyngeal cancer (OPC) examinations, we assessed mechanisms of behavior change among individuals receiving an OPC examination for the first time. We used data from 2 waves of telephone surveys of individuals residing in 36 rural census tracts in northern Florida (n = 806). The second survey occurred after our media intervention. We developed media messages and modes of message delivery with community members via focus groups and intercept interviews. We performed a mediation analysis to examine behavior change mechanisms. Greater exposure to media messages corresponded with heightened concern about OPC. Heightened concern, in turn, predicted receipt of a first-time OPC examination, but only among men. We extended earlier studies by measuring an outcome behavior (receipt of an OPC examination) and demonstrating that the putative mechanism of action (concern about the disease) explained the link between a media intervention and engaging in the target behavior. Improving the quality of media campaigns by engaging community stakeholders in selecting messages and delivery methods is an effective strategy in building public health interventions aimed at changing behaviors.


Technique of anterior urethra urethroplasty using tunica albuginea of corpora cavernosa.
Over previous years, urethral stricture has constantly created a great problem in efforts to find a permanent cure for it. We describe a technique of anterior urethroplasty using tunica albuginea of corpora cavernosa. After a midline penoscrotal incision, the bulbar or penile urethra along with corpus spongiosum was dissected from the corpora cavernosa. Urethra was then rotated dorsally and the stricture was opened along its whole length. The walls of the slit urethra, along with the tunica albuginea of the corpus spongiosum, were sutured to the tunica albuginea of the corpora cavernosa at the 5 and 7 o'clock position after passing an all silicon catheter. We performed this technique on 79 male patients, having anterior urethral stricture, ranging 18-60 years of age (mean, 46 years). The etiology of stricture was trauma in 54, instrumentation in 12, infection in 10 and unknown in three. Follow ups were done at 4, 12 and 24 months by assessing patients' satisfaction rate along with a pre- and postoperative urethrogram, labeled as "good", "fair" and "poor". Good and fair results were considered as successful. The overall success rate was 94.9%. The success rate remained same at 4 months (64 + 11) and decreased to 93.7% (63 + 11) at 12 months and 89.9% (61 + 10) at 24 months. These observations show that anterior urethroplasty using tunica albuginea of corpora cavernosa have produced satisfactory results and are comparable with any other technique of urethroplasty. Thus, we strongly recommend the use of tunica albuginea of corpora cavernosa for anterior urethroplasty, which is histologically similar and anatomically located near the stricture.


Flow-injection chemiluminescence determination of haemoglobin in the blood.
In this study, a sensitive and simple flow-injection chemiluminescence (CL) method was developed for the quantitative analysis of haemoglobin. The method is based on the ability of haemoglobin to enhance the CL signal generated by a H(2)O(2) -K(4) Fe(CN)(6) -fluorescein alkaline system enhanced by CdTe quantum dots. Under the optimized conditions, haemoglobin can be detected in concentration range 7.35 × 10(-9) -2.5 × 10(-6) mol/L, with a detection limit (3σ) of 1.8 × 10(-9) mol/L and a relative standard deviation (RSD; for 5 × 10(-7) mol/L haemoglobin) of 2.06% (n = 11). The present CL method was successfully applied for the determination of haemoglobin in three kinds of blood samples taken from an infant, an adult man, an adult woman and two reference samples. Compared with previous reports, the CL method described in this work is simple and rapid, with high sensitivity.


Overproduction of efflux pumps caused reduced susceptibility to carbapenem under consecutive imipenem-selected stress in Acinetobacter baumannii.
Acinetobacter baumannii is an important pathogen in the nosocomial infections worldwide. Combining with carbapenemases, efflux pumps and outer membrane proteins (OMPs) have been thought to affect the development of carbapenem resistance in A. baumannii. This study aimed to investigate the contributions of different efflux pumps and OMPs in developing carbapenem resistance in a clinical isolate of A. baumannii and reveal the possible mechanism of overproduction of main efflux pumps. In this study, an imipenem-susceptible clinical isolate was identified as A. baumannii and named SZE. Several common carbapenemases were detected by polymerase chain reaction (PCR). Imipenem-selected mutants were selected from SZE by serial subcultivations on Mueller-Hinton agar, and the minimum inhibitory concentration (MIC) was detected. Gene expressions of four families of efflux pumps, five OMPs, and blaOXA-51 were determined by reverse transcription quantitative PCR, and comparisons were made between SZE strain and the imipenem-selected mutants. The adeRS system in SZE and its mutant was sequenced and aligned. Under consecutive imipenem-selected stress, the MIC to imipenem increased gradually from 0.125 μg/mL to 8 μg/mL. The effect of resistance inducement was almost neutralized when treated with an efflux pump inhibitor. The expression of efflux pumps, adeB, adeG, and adeJ, was increased by 6.9-, 4.0-, and 2.1-fold in mutants, respectively, compared to SZE. A single mutation (G to A) at position 58 was detected in the regulatory adeRS system and possibly upregulated the adeB expression, and then affected the carbapenem resistance in A. baumannii strains. In conclusion, under consecutive imipenem-selected stress in vitro, A. baumannii strain evolved the ability to reduce susceptibility to a variety of antimicrobials by overproduction of efflux pumps. Especially, the resistance-nodulation-cell division super family and a nucleotide mutant in adeRS regulating system caused the overexpression of adeABC.


Rate and Predictors of Hesitancy toward SARS-CoV-2 Vaccine among Type 2 Diabetic Patients: Results from an Italian Survey.
Vaccine hesitancy (VH) has been identified as one of the major health concerns of our time by the World Health Organization. It may prove especially detrimental in the light of the ongoing SARS-CoV-2 pandemic, as vaccination campaigns still represent the primary strategy against the detrimental consequences of the pandemic. Among patients suffering from type 2 diabetes mellitus (DB), who are particularly vulnerable to COVID-19, VH might represent an even more serious threat. Therefore, our study focuses on identifying potential determinants of VH among patients with type 2 diabetes. Study participants (n = 1176) filled in a two-section online self-administered questionnaire, answering questions regarding demographic and anamnestic data, as well as their intention to accept any vaccination against COVID-19. Some possible reasons underlying VH were investigated as well. An overall hesitancy rate of 14.2% was registered. Data showed how older age, male gender, higher education level, and having been vaccinated for seasonal influenza in 2020-2021 were associated with a significantly higher propensity to receive the COVID-19 vaccine. On the contrary, having experienced adverse effects following past vaccinations was a negative predictor. In addition to confirming an array of predictors of VH, we found a worryingly high prevalence of VH among diabetics, who have been shown to be particularly exposed to severe COVID-19 and death. These findings may be useful in planning targeted action toward acceptance improvement and enhancing the efficacy of vaccination campaigns.


Selective modulation of glutathione levels in human normal versus tumor cells and subsequent differential response to chemotherapy drugs.
Cellular glutathione (GSH) levels were found to be 7-fold higher in a human lung adenocarcinoma cell line (A549) than in a normal human lung fibroblast line (CCL-210). Differential modulation of cellular GSH was explored in these cell lines by (a) stimulation of GSH synthesis by oxothiazolidine-4-carboxylate (OTZ) and (b) inhibition of GSH synthesis by buthionine sulfoximine (BSO). In the tumor cell line, OTZ treatment had no effect; however, GSH levels of 140-170% of control were achieved in the normal fibroblast line. With BSO, the normal cell line was depleted of GSH at a faster relative rate than with the tumor line. Within 7 h, 5% GSH remained in the CCL-210 line while approximately 40% GSH remained in the A549 line. Survival response of normal versus tumor cell lines to selected chemotherapy drugs was compared following modulation of GSH levels. OTZ pretreatment of the A549 line provided no protection to a 1-h exposure to melphalan, cisplatin, or bleomycin; however, OTZ pretreatment of CCL-210 elevated GSH and provided protection to melphalan, cisplatin, and bleomycin (protection ratios at 5% survival of 1.2, 1.4, and 1.4, respectively). Neocarzinostatin toxicity in the normal CCL-210 line pretreated with BSO was greatly reduced (protection ratio at 50% survival = 5.0). The same BSO treatment to A549 cells (40% GSH remaining) yielded a similar survival curve to control cells. These studies demonstrate that selective differential chemotherapy responses of normal versus tumor cells is possible by manipulating the GSH synthetic cycle. Should basic phenotypic differences with regard to reductive capacity exist in vivo, such manipulation in GSH levels might yield a therapeutic gain for carefully selected chemotherapy drugs.


Nanomaterials in Advanced, High-Performance Aerogel Composites: A Review.
Aerogels are one of the most interesting materials of the 21st century owing to their high porosity, low density, and large available surface area. Historically, aerogels have been used for highly efficient insulation and niche applications, such as interstellar particle capture. Recently, aerogels have made their way into the composite universe. By coupling nanomaterial with a variety of matrix materials, lightweight, high-performance composite aerogels have been developed for applications ranging from lithium-ion batteries to tissue engineering materials. In this paper, the current status of aerogel composites based on nanomaterials is reviewed and their application in environmental remediation, energy storage, controlled drug delivery, tissue engineering, and biosensing are discussed.


Seven COVID-19 Patients Treated with C-Reactive Protein (CRP) Apheresis.
Background: The fulminant course of COVID-19, triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), presents with a high mortality rate and still lacks a causative treatment. C-reactive protein (CRP) has been shown to increase dramatically during the disease progression and correlates with deleterious outcomes. Selective CRP apheresis can reduce circulating CRP levels fast and effective. Methods: Seven hospitalized patients with documented severe COVID-19 progression, elevated CRP plasma levels (>100 mg/L) and signs of respiratory failure were treated with CRP apheresis. Two to twelve CRP apheresis sessions were performed generally in 24 h time intervals and depending on CRP plasma levels. Results: All patients had comorbidities. CRP apheresis reduced CRP plasma levels by up to 84% within a few hours, without exhibiting side effects in any patient. Despite signs of severe lung infiltration in all patients, only one patient died. The other patients showed improvements within the chest X-ray after CRP apheresis and were able to recover regardless of intubation and/or ECMO (4 patients). All remaining six patients were discharged from the hospital in good clinical condition. Conclusions: This case series presents a mortality rate of only 14%, which is dramatically lower than expected from the presented CRP levels as well as comorbidities and ventilation requirements. Our clinical observations regarding the here presented seven patients support the hypothesis that CRP is a candidate to be therapeutically targeted in the early stage of severe COVID-19.


Rare Disease Research Partnership (RAinDRoP): a collaborative approach to identify the top 15 research priorities for rare diseases.
Background: The Rare Disease Research Partnership (RAinDRoP) was established in 2018 to bring together a wide variety of diverse voices in the rare disease community in Ireland and form a research partnership. This approach enabled clinicians, patients, carers and researchers to work together to identify top research priorities for rare diseases, which focused on a life-course perspective rather than a disease-specific need. Methods: A participatory multiple phase approach was used to identify research priorities for rare diseases. The research process involved three main phases: Phase I, Public Consultation Survey on Research in Rare Diseases in Ireland (PCSRRDI); Phase II, Research Prioritisation Workshop (RPW); Phase III, Follow-up Public Consultation and Prioritisation Survey (FWPCPS). Results: In total, 240 individuals completed the phase I PCSRRDI, which comprised of a cross-section of health care professionals, researchers and people living with rare diseases. One thousand and fifteen statements were collected, reflecting issues and shared challenges in rare diseases. A shortlisting step by step was used to identify any statements that had received a total score of above 50% into 10-12 researchable questions or statements per the theme for the phase II workshop. Phase II was focused on three main themes: (1) Route to Diagnosis, (2) Living with Rare Disease, (3) Integrated and Palliative Care. In total, 62 individuals attended the overall workshop; 42 participated in the prioritisation sessions. A cross-section of health care professionals, researchers and people living with rare diseases were engaged at each workshop. Seventy-five individuals completed the final phase III public ranking by priority responses, and they ranked the top 15 research priorities defined by the multi-stakeholders at the phase II consensus meeting. Conclusions: This study identified priorities for rare diseases research aimed at improving the health and wellbeing of people living with rare diseases.


A case of a borderline-broad complex tachycardia.
Prompt and correct treatment of broad complex tachycardias in the emergency department can often be life-saving to the patient and satisfying for the emergency physician. They, however, are often a diagnostic challenge. Here, we present a case of posterior fascicular ventricular tachycardia, an idiopathic form of ventricular tachycardia that occurs in patients without coronary artery disease and verapamil sensitive. The differential diagnoses of posterior fascicular ventricular tachycardia and supraventricular tachycardia with aberrancy will also be discussed.


Infantile acropustulosis.
A case of infantile acropustulosis is described. The condition responded to sulfones while it was not affected by any other therapy. Histologically, subcorneal pustules were found; persistent modest eosinophilia and eosinophils were present in the vesicular content, a feature never observed before. The significance of this finding is discussed.


Results of chimney modification technique in ureterointestinal anastomosis of Hautmann ileal neobladder in bladder cancer.
To evaluate the surgical technique and functional outcome of a new application of the chimney modification to the popular Hautmann ileal neobladder. This modification used 3-5 cm chimney tubularized ileal segment for the bilateral ureterointestinal anastomosis. Between December 2000 and July 2004, 15 patients (14 men, 1 woman) with invasive bladder cancer underwent radical cystectomy and Hautmann neobladder with chimney modification at Siriraj Hospital, Bangkok. Mean age was 61.7 years (range, 43-72 years). Perioperative morbidity, early and late urinary diversion-related complications, other surgical complications, follow-up results of ureterointestinal anastomosis, renal function and metabolic disorders were evaluated. Patients were interviewed about their continence, voiding function and potency. At a mean follow-up of 29.5 months, two patients had died of cancer progression. Of the 15 patients, nine (60%) had 10 early complications. Eight complications were related to the neobladder and two were not. Three (20%) patients had three late complications. Two complications were neobladder-related and one was not. There was no perioperative mortality. There was no ureteroileal anastomosis stricture in this series. Neobladder-ureteral reflux was demonstrated in eight of 22 ureteral units in 11 patients in whom cystography was performed. All patients had normal upper urinary tract without evidence of urinary obstruction. All 14 men (93% of study sample) had spontaneous urination, normal renal function and no metabolic acidosis. Good and satisfactory continence in the day and night were 93% and 73%, respectively. All male patients experienced impotence postoperatively. Only one sought treatment and was successfully treated with sildenafil. The one woman in this study required intermittent catheterization to empty the neobladder completely. She also had renal insufficiency with serum creatinine of 2.2 mg/dL and hyperchloraemic metabolic acidosis. New chimney modification in Hautmann ileal neobladder is simple and safe. Complications are acceptable. Follow-up results of renal and voiding functions are satisfactory. This operation can maintain good quality of life for patients with bladder cancer undergoing radical cystectomy.


Extramedullary versus intramedullary tibial alignment guides for total knee arthroplasty.
This retrospective study evaluated whether intramedullary or extramedullary tibial alignment guides are more accurate in assuring correct tibial component positioning in total knee arthroplasties (TKAs). Fifty-five TKAs were performed with the only difference being whether an intramedullary (31) or extramedullary (24) cutting guide was used. Pre- and postoperative tibiofemoral angle, tibial component alignment angle, and femoral component alignment angles were measured and the results were statistically analyzed. We also performed a subgroup analysis on the preoperative varus knees to determine if the presence of a varus deformity would have better results with either the intramedullary or extramedullary cutting guide. The 2-sample t test was used to compare the results of the two groups. The results showed no statistical difference in alignment of the tibial component when using the intramedullary or extramedullary guides.


Determination of effective dosage of GH-releasing factor for blood GH responses in mithun (Bos frontalis).
A study was undertaken to determine the effective dosage of GH-releasing hormone (GRF) required to produce blood GH response in mithun (Bos frontalis), a semi-wild ruminant species. For the purpose, 12 mithuns averaging 11.5 months of age and 146 kg body weight (BW) were randomly assigned to receive GRF (n = 12), administered at 0 (normal saline), 5, 10 and 20 mug per 100 kg BW. Blood samples were collected prior to and after GRF administration at -60, -45, -30, -15, -10, -5, 0 min and 5, 10, 15, 30 and thereafter, at 15-min interval up to 8 h post-GRF were assayed for plasma GH. For all the dosages, the pre-treatment GH concentrations and corresponding area under GH response curve (AUC) were similar (p > 0.05). The post-GRF plasma GH responses to different dosages of GRF viz. 5, 10 and 20 mug per 100 kg BW and corresponding AUCs were higher (p < 0.05) than those recorded in normal saline-treated controls. The GH responses to 10 and 20 mug GRF per 100 kg BW and corresponding AUCs were higher (p < 0.05) than those registered in mithuns administered with 5 mug GRF per 100 kg BW. Interestingly, post-GRF concentration of plasma GH and AUCs were not different for 10 and 20 mug GRF per 100 kg BW dosages. In all animals treated with GRF, a peak of GH was registered within 10 to 20 min post-GRF. Following 5 mug GRF per 100 kg BW, GH concentrations were maintained at higher level for 90 min post-GRF and thereafter became similar to that of controls and it was 435 min for 10 and 20 mug GRF per 100 kg BW dosages. In conclusion, our results suggest that 10 mug GRF per 100 kg BW is the dosage, which can be used for augmentation of mithun production.


A large-scale measurement, analysis and modelling of electromagnetic radiation levels in the vicinity of GSM/UMTS base stations in an urban area.
The present study analyses the electric field radiating from the GSM/UMTS base stations located in central Malatya, a densely populated urban area in Turkey. The authors have conducted both instant and continuous measurements of high-frequency electromagnetic fields throughout their research by using non-ionising radiation-monitoring networks. Over 15,000 instant and 13,000,000 continuous measurements were taken throughout the process. The authors have found that the normal electric field radiation can increase ∼25% during daytime, depending on mobile communication traffic. The authors' research work has also demonstrated the fact that the electric field intensity values can be modelled for each hour, day or week with the results obtained from continuous measurements. The authors have developed an estimation model based on these values, including mobile communication traffic (Erlang) values obtained from mobile phone base stations and the temperature and humidity values in the environment. The authors believe that their proposed artificial neural network model and multivariable least-squares regression analysis will help predict the electric field intensity in an environment in advance.


Pharmacogenetics and personalised medicine.
The traditional concern of pharmacogenetics was Mendelian (monogenic) variation, which visibly affected some drug responses. Pharmacogenetics was broadened by the observation that multifactorial genetic influences, in conjunction with environmental factors, usually determine drug responses. Variability of gene expression, a new theme of the science of genetics, also affects pharmacogenetics; for example, enhanced enzyme activity does not necessarily indicate a mutation, but may be the consequence of a drug-induced enhancement of gene expression. Methodological advances permit the conversion of pharmacogenetics into the broad practice of pharmacogenomics; this improves the possibility of identifying genetic causes of common diseases, which means establishing new drug targets, thereby stimulating the search for new drugs. While the main medical effect of pharmacogenetics was an improvement of drug safety, pharmacogenomics is hoped to improve drug efficacy. On the way to personalized medicine, we may stepwise improve the chances of choosing the right drug for a patient by categorizing patients into genetically definable classes that have similar drug effects (as, for example, human races, or any population group carrying a particular set of genes). It is wise to expect that, even after we have reached the goal to establish personalized medicine, we will not have eliminated all uncertainties.


[Enzymatic differences in mycobacteria. Ribitol dehydrogenase].
Contrary to the tubercle Bacilli (H37Ra, BCG), Mycobacterium phlei has a ribitol-NAD dehydrogenase (that also oxidizes, although to a lesser extent, erythritol and glycerol). This difference is observed with the Bacteria grown on Sauton's medium, as well as after their adaptation to ribitol. The extracts of all these Mycobacteria reduce, NADP in the presence of glycerol, ribitol or erythritol, though very slowly.


Hybrid Machine Learning-Enabled Potential Energy Model for Atomistic Simulation of Lithium Intercalation into Graphite from Plating to Overlithiation.
Graphite is one of the most widely used negative electrode materials for lithium ion batteries (LIBs). However, because of the rapid growth of demands pursuing higher energy density and charging rates, comprehensive insights into the lithium intercalation and plating processes are critical for further boosting the potential of graphite electrodes. Herein, by utilizing the dihedral-angle-corrected registry-dependent potential (DRIP) (Wen et al., Phys. Rev. B 2018, 98, 235404), the Ziegler-Biersack-Littmark (ZBL) potential (Ziegler and Biersack, Astrophysics, Chemistry, and Condensed Matter; 1985, pp 93-129), and the machine learning-based spectral neighbor analysis (SNAP) potential (Thompson et al., J. Comput, Phys. 2015, 285, 316-330), we have successfully trained a hybrid machine learning-enabled potential energy model capable of simulating a wide spectrum of lithium intercalation scenario from plating to overlithiation. Our extensive atomistic simulations reveal the trapping of intercalated lithium atoms close to the graphite edges due to high hopping barriers, resulting in lithium plating. Furthermore, we report a stable dense graphite intercalation compound (GIC) LiC4 with a theoretical capacity of 558 mAh/g, wherein lithium atoms occupy alternating upper/lower graphene hollow sites with a nearest Li-Li distance of 2.8 Å. Surprisingly, following the same lithium insertion manner would allow the nearest Li-Li distance to be retained until the capacity reaches 845.2 mAh/g, corresponding to a GIC of LiC2.6. Hence, the present study demonstrates that the hybrid machine learning approach could further extend the scope of machine learning energy models, allowing us to investigate the lithium intercalation into graphite over a wide range of intercalation capacity to unveil the underlying mechanisms of lithium plating, diffusion, and discovery of new dense GICs for advanced LIBs with high charging rates and high energy densities.


Pharmacological and biochemical effects of Ginkgo biloba extract on learning, memory consolidation and motor activity in old rats.
Effect of administration of the standardized extract of Ginkgo biloba leaves (EGb 761) on learning, memory and exploratory behavior was estimated in water maze and hole-board tests. Rats (18-month old) received for three months EGb 761 at doses: 50, 100 and 150 mg/kg b.w. per day. After completion of the behavioral experiment, concentrations of neurotransmitters were estimated in selected brain regions. ANOVA demonstrated significant differences in the content of monoamines and metabolites between the treatment groups compared to the control. The increased level of 5-hydroxytryptamine (5-HT) in the hippocampus and 5-HIAA (5-HT metabolite) in the prefrontal cortex correlated positively with the retention of spatial memory. Positive correlation between platform crossings in SE during the probe trial and neurotransmitter turnover suggest improvement of spatial memory. Long-term administration of Ginkgo biloba extract can improve spatial memory and motivation with significant changes in the content and metabolism of monoamines in several brain regions.


The role of child care in a community-wide outbreak of hepatitis A.
To evaluate the role of child care centers in a community-wide hepatitis A epidemic. We analyzed surveillance data during an epidemic in Maricopa County, Arizona, from January to October 1997 and conducted a case-control study using a sample of cases reported from June to November. Cases were physician-diagnosed and laboratory confirmed; control subjects were frequency matched by age and neighborhood. Information regarding hepatitis A risk factors, including child care-related exposures, was collected. Characteristics of all licensed child care centers in the county were obtained through review of computerized lists from the Arizona Office of Child Day Care Licensing. Surveillance data were linked to the child care list to determine which centers had reported hepatitis A cases. We conducted univariate and multivariate conditional logistic analyses and calculated population attributable risks (PAR). In total, 1242 cases (50/100 000 population) were reported. The highest rates occurred among people aged 0 to 4 (76/100 000), 5 to 14 (95/100 000), and 15 to 29 (79/100 000) years. The most frequently reported risk factor was contact with a hepatitis A patient (45%). However, nearly 80% of these contacts were with individuals who attended or worked in a child care center. Overall, child care center-related contact could have been the source of infection for 34% of case-patients. In the case-control study, case-patients (n = 116) and control subjects (n = 116) did not differ with respect to demographic characteristics. A total of 51% of case-patients compared with 18% of control subjects reported attending or working in a child care setting (direct contact; adjusted odds ratio [OR]: 6.0; 95% confidence interval [CI]: 2.1-23.0) or being a household contact of such a person (indirect contact; OR: 3.0; 95% CI: 1.3-8.0). In age-stratified analyses, the association between hepatitis A and direct or indirect contact with child care settings was strongest for children <6 years old and adults aged 18 to 34 years. Household contact with a person with hepatitis A also was associated with hepatitis A (OR: 9.2; 95% CI: 2.6-58.2). The presence of a child <5 years old in the household was not associated with hepatitis A. The estimated PAR for direct child care contact was 23% (95% CI: 16-34), for indirect child care contact was 21% (95% CI: 13-35), and for any child care contact was 40% (95% CI: 30-53). Information on 1243 licensed child care centers was obtained, with capacity ranging from 5 to 479 slots (mean: 87). Thirty-four (2.7%) centers reported hepatitis A cases. Centers that had a mean capacity of >50 children were more than twice as likely to have had a reported case of hepatitis A (OR: 2.6; 95% CI: 1.1-6.7). Among the 747 centers that accepted >50 children, having infant (OR: 3.7; 95% CI: 1.6-8.3), toddler (OR: 6.3; 95% CI: 2.2-20.0), or full-day service (OR; undefined; 95% CI: 1.7- ~) was associated with having a reported case of hepatitis A. In Maricopa County, people associated with child care settings are at increased risk of hepatitis A, and child care attendees may be an appropriate target group for hepatitis A vaccination. Considering the estimated proportion of children who attended child care and were old enough to receive hepatitis A vaccine (>/=2 years of age) and the calculated PAR, approximately 40% of cases might have been prevented if child care center attendees and staff had been vaccinated. However, epidemiologic studies indicate that the proportion of cases that are attributable to child care center exposure varies considerably among counties, suggesting that this exposure may be associated with an increased risk of hepatitis A in some communities but not in others. To prevent and control hepatitis A epidemics in communities, the Advisory Committee on Immunization Practices and the American Academy of Pediatrics have adopted a long-term strategy of routine vaccination of children who live in areas with consistently elevated hepatitis A rates. After demonstrating cost-effectiveness, a rule was implemented in January 1999 to require hepatitis A vaccination of all children who are aged 2 to 5 years and enrolled in a licensed child care facility in Maricopa County. Other communities with similar epidemiologic features might consider routine vaccination of child care center attendees as a long-term hepatitis A prevention strategy. Consistent with current recommendations, in communities with persistently elevated hepatitis A rates where child care center attendance does not play an important role in hepatitis A virus transmission in the community, child care centers may nonetheless provide a convenient access point for delivering hepatitis A as well as other routine childhood vaccinations.


Relationship between hip and knee kinematics in athletic women during cutting maneuvers: a possible link to noncontact anterior cruciate ligament injury and prevention.
The purposes of this study were to compare lower-extremity kinematics during a 45 degrees and 90 degrees cutting maneuver and to examine the relationships between lower-extremity rotations during these maneuvers. The hypotheses tested were that greater internal hip and knee rotation angles would be observed during the cutting maneuver at a 90 degrees angle (90 degrees cut) compared with the maneuver performed at a 45 degrees angle (45 degrees cut) and that the increased internal hip and knee rotation would be related to increased knee abduction measures. Nineteen athletes from women's soccer teams (17.6 +/- 2.1 yr, 165.6 +/- 8.2 cm, 60.2 +/- 5.6 kg) were instructed to jump across a line and cut at the appropriate angle (either 45 degrees or 90 degrees side-step cut) and in the appropriate direction. Lower-extremity kinematic measures were taken at peak force during the stance phase. Hip internal rotation and knee internal rotation (p = 0.008) were increased during the 90 degrees cut compared with the 45 degrees cut. Mean hip flexion (p < 0.001) was also greater in the 90 degrees cut. The only significant predictor of knee abduction during both tasks was hip adduction (R = 0.49). The findings indicate that the mechanisms underlying increased knee abduction measures in athletic women during cutting tasks were primarily coronal plane motions at the hip. Trunk and hip focused strength neuromuscular training may improve the ability of athletic women to increase control of lower-extremity alignment. Therefore, these women may decrease dangerous knee loads that result from increased hip adduction during dynamic tasks, thus decreasing anterior cruciate ligament injury risk.


Robust Production of Ultrahigh Surface Area Carbon Sheets for Energy Storage.
Nanostructured carbon materials play essential roles in electrochemical energy storage devices. However, scalable production of high surface area carbon with a cost-effective process while controlling the morphology is challenging. Herein, a one-step procedure to produce carbon sheets with very high specific surface area up to 3411 m2 g-1 by direct pyrolysis of dipotassium ethylene diamine tetraacetate is reported. Unlike that of biomass-pyrolyzed carbons, the surface area of prepared carbon sheets is not sensitive to pyrolysis conditions (e.g., heating temperature and time), which makes the production robust and scalable. Moreover, the pore structure is stable against posttreatments, including solvent washing, which are detrimental to that of graphene-based soft sheet assemblies. When used as supercapacitor electrodes, the ultrahigh surface area carbon sheets (HSACS) show a high specific capacitance of 268 F g-1 at 5 mV s-1 , and retain 70% of the capacitance at 100 times higher scan rate in 6 m KOH aqueous electrolyte. Furthermore, the HSACS also exhibit a high specific capacitance of 266 F g-1 within a 1.6 V symmetric supercapacitor potential window in 2 m Li2 SO4 aqueous electrolyte. The symmetric supercapacitor delivers a maximum specific energy of 23.6 W h kg-1 and high power density of 6.4 kW kg-1 .


Wilms Tumor of the Uterus.
Wilms tumor (WT) is an uncommon malignant neoplasm that occurs predominantly in the kidney of pediatric patients; its extrarenal counterpart is exceedingly rare. We present the case of an adult female diagnosed with uterine WT. Following hysterectomy due to a uterine mass, histopathologic examination demonstrated a triphasic malignancy composed of epithelial, stromal, and blastemal elements. The characteristic morphologic features, which were supported by immunohistochemical analysis, were diagnostic of WT of the uterus. A summary of the main clinicopathologic parameters, along with a review of all previously reported cases, are described.


High SSR diversity but little differentiation between accessions of Nordic timothy (Phleum pratense L.).
A large collection of genebank accessions of the hexaploid outcrossing forage grass species timothy (Phleum pratense L.) was for the first time analysed for SSR diversity on individual, population and regional level. Timothy is the most important forage grass species in the Nordic countries. Eighty-eight timothy accessions from Nordic countries and eight accessions around Europe were analysed with recently developed simple sequence repeat (SSR) markers. Timothy proved to be very polymorphic: the 13 selected SSRs amplified a total of 499 polymorphic alleles, the number of alleles per SSR locus varying from 15 to 74. Taking all SSR alleles together, the observed number in each accession ranged from 95 to 203. Levels of diversity were found to be significantly different between countries, vegetation zones and different cultivar types. However, the differentiation between accessions was low: most of the variation (94%) in the studied timothy material was due to variation within accessions and only 5% was between accessions and 1% between countries. Lack of geographical differentiation may reflect the outcrossing and hexaploid nature of timothy. Our results showed that neutral SSR markers are suitable for demonstrating levels of diversity but not alone adequate to resolve population structure in timothy. Nordic timothy material seems to be diverse enough for breeding purposes and no decline in the level of diversity was observed in varieties compared to wild timothy populations. Challenges in analysing SSR marker data in a hexaploid outcrosser were discussed.


Determination of corneal asphericity after myopia surgery with the excimer laser: a mathematical model.
To determine the theoretical change of corneal asphericity within the zone of laser ablation after a conventional myopia treatment, which conforms to Munnerlyn's paraxial formula and in which the initial corneal asphericity is not taken into consideration. The preoperative corneal shape in cross section was modeled as a conic section of apical radius R(1) and shape factor p(1). A myopia treatment was simulated, and the equation of the postoperative corneal section within the optical zone was calculated by subtracting the ablation profile conforming to a general equation published by Munnerlyn et al. The apical radius of curvature r(2) of the postoperative profile was calculated analytically. The postoperative corneal shape was fitted by a conic section, with an apical radius equal to r(2) and a shape factor p(2) equal to the value that induced the lowest sum of horizontal residuals and the lowest sum of squared residuals. These calculations were repeated for a range of different dioptric treatments, initial shape factor values, and radii of curvature to determine the change of corneal asphericity within the optical zone of treatment. Analytical calculation of r(2) showed it to be independent of the initial preoperative shape factor p(1). The determination of p(2) was unambiguous, because the same value induced both the lowest sum of residuals and the lowest sum of the squared residuals. For corneas initially prolate (p(1) < 1), prolateness increased (p(2) < p(1) < 1), whereas for oblate corneas (p(1) > 1), oblateness increased (p(2) > p(1) > 1) within the treated zone after myopia treatment. This trend increased with the increasing magnitude of treatment and decreased with increasing initial apical radius of curvature R(1). After conventional myopic excimer laser treatment conforming to Munnerlyn's paraxial formula, the postoperative theoretical corneal asphericity can be accurately approximated by a best-fit conic section. For initially prolate corneas, there is a discrepancy between the clinically reported topographic trend to oblateness after excimer laser surgery for myopia and the results of these theoretical calculations.


Low-dose oral tolerance due to antigen in the diet suppresses differentially the cholera toxin-adjuvantized IgE, IgA and IgG response.
Cholera toxin (CT) is used as a mucosal adjuvant amongst other applications for studying food allergy because oral administration of antigen with CT induces an antigen-specific type 2 response, including IgE and IgA production. Previously established oral tolerance due to antigen in the diet may radically impact on the CT-adjuvantized immune response. The present study served to evaluate the effect of previously established low-dose oral tolerance on the CT-adjuvantized immune response towards a food antigen. Mice fed a diet containing microgram levels of the soy protein Kunitz soy-trypsin inhibitor (KSTI) (F0 mice) and mice fed a soy-free diet (F2 mice) were orally immunized with KSTI and CT. KSTI-specific serum IgG1, IgG2a, IgA and IgE and fecal IgA were monitored. KSTI-stimulated cell proliferation and interleukin (IL)-6 production were determined. The anti-KSTI IgE and IgA responses in the F0 mice were substantially suppressed, while the IgG1 and IgG2a responses were not suppressed after five oral immunizations. The response suppression tended to decline with increasing numbers of immunizations suggesting that the suppression could be overcome by multiple immunizations. However, cell proliferation and IL-6 production were clearly suppressed even after five immunizations. Priorly established low-dose oral tolerance considerably suppressed the CT-adjuvantized KSTI-specific IgE, IgA and cellular immune response but only weakly and transiently the IgG response. The results revealed that low-dose oral tolerance includes the mucosal IgA response and that CT, albeit mediating an antigen-specific response, does not fully abrogate previously established oral tolerance.


Expression of connexin48.5, connexin44.1, and connexin43 during zebrafish (Danio rerio) lens development.
Connexins (Cx), the protein units of gap junctions, play important roles in lens development and homeostasis. Here, we report the mRNA expression patterns of zebrafish Cx48.5, Cx44.1, Cx43 during lens development. The expression of all three connexins in the adult lens was first confirmed by reverse transcriptase-polymerase chain reaction. By whole-mount in situ hybridization, we detected Cx48.5 expression throughout the lens, except the lateral lens epithelium, at 36 hours postfertilization (hpf). The pattern remained the same at 2 days postfertilization (dpf). By 3 and 4 dpf, Cx48.5 expression was restricted to the differentiating lens fibers in the equatorial and medial regions. Cx44.1 was expressed in a similar manner as Cx48.5 from 36 hpf to 4 dpf. However, Cx44.1 expression was also detected in the lens at 24 hpf. Cx43 expression was detected throughout the lens at 24 and 36 hpf but became restricted to the lateral epithelium at later stages.


Economic value of trees in the estate of the Harewood House stately home in the United Kingdom.
The estates of stately homes or manor houses are an untapped resource for assessing the ecosystem services provided by trees. Many of these estates have large collections of trees with clear value in terms of carbon storage, runoff prevention, and pollution removal along with additional benefits to biodiversity and human health. The estate of Harewood House in North Yorkshire represents an ideal example of such a stately home with a mixture of parkland and more formally planted gardens. The trees in each type of garden were analysed for height, diameter at breast height and light exposure. The data were then processed in iTrees software to generate economic benefits for each tree in both gardens. The analysis found that the larger North Front parkland garden had greater total benefits but the more densely planted formal West Garden had the greater per hectare value. In total, the trees on Harewood House estate are estimated to provide approximately £29 million in ecosystem service benefits. This study is the first to analyse the trees of stately homes for economic benefits and highlights that the trees are a valuable commodity for the estates. This should be considered in future planning and management of such estates.