Falls, healthcare resources and costs in older adults with insomnia treated with zolpidem, trazodone, or benzodiazepines.
Falls are the leading cause of injury-related death among older Americans. While some research has found that insomnia heightens falls, health care resource utilization (HCRU) and costs, the impact of insomnia treatments on fall risk, mortality, HCRU and costs in the elderly population, which could be of substantial interest to payers, has not been fully elucidated. This study evaluated the risk of falls and related consequences among adults ≥ 65 years of age treated with common prescription medications for insomnia compared with non-sleep disordered controls. This was a retrospective cohort analysis of deidentified Medicare claims from January 2011 through December 2017. Medicare beneficiaries treated for insomnia receiving zolpidem extended-release, zolpidem immediate-release, trazodone, or benzodiazepines were matched with non-sleep disordered controls. The main outcomes were falls, mortality, healthcare resource utilization (HCRU), and medical costs during the 12 months following the earliest fill date for the insomnia medication of interest. Generalized linear models controlled for several key covariates, including age, race, sex, geographic region and Charlson Comorbidity Index score. The study included 1,699,913 Medicare beneficiaries (59.9% female, mean age 75 years). Relative to controls, adjusted analyses showed that beneficiaries receiving insomnia medication experienced over twice as many falls (odds ratio [OR] = 2.34, 95% CI: 2.31-2.36). In adjusted analyses, patients receiving benzodiazepines or trazodone had the greatest risk. Crude all-cause mortality rates were 15-times as high for the insomnia-treated as controls. Compared with controls, beneficiaries receiving insomnia treatment demonstrated higher estimated adjusted mean number of inpatient, outpatient, and emergency department visits and longer length of inpatient stay. All-cause total adjusted mean costs were higher among insomnia treated patients ($967 vs $454). Individuals receiving insomnia treatment had an increased risk of falls and mortality and higher HCRU and costs compared with matched beneficiaries without sleep disorders. Trazodone and benzodiazepines were associated with the greatest risk of falls. This analysis suggests that significant risks are associated with common, older generation insomnia medication treatments in the elderly. Nonetheless, these results should be interpreted with caution as the use of these medications may be indicative of underlying morbidity with potential for residual confounding.


Electroencephalography burst suppression in a patient with dengue encephalopathy: A case report.
To report a rare case of dengue fever presenting with reversible encephalopathy and burst suppression in the EEG. We describe an 85-year-old man with dengue encephalopathy and EEG burst suppression and review the related literature. The patient presented with an acute comatose state and absent brainstem reflexes. Blood pressure, pulse rate, temperature and oxygen saturation were 94/49mmHg, 82beats/min, 34.7 degrees C, and 83% respectively. Thrombocytopenia and skin rash were found initially. Oxygen saturation was 100% immediately after endotracheal intubation and mechanical ventilation. On the second day he remained comatose with EEG burst suppression but blood pressure and temperature were within normal limits. He regained consciousness and was alert on the 12th day and there was normalization of EEG and thrombocytopenia. Patients with dengue fever may present as encephalopathy with EEG burst suppression. EEG burst suppression does not necessarily suggest a poor prognosis in patients with dengue fever.


Should long-segment cervical fusions be routinely carried into the thoracic spine? A multicenter analysis.
Although recommendations for caudal "end level" in posterior cervical reconstruction remain highly variable, the benefits of routine extension of posterior cervical fusions into the thoracic spine remain unclear. We compared clinical and radiographic outcomes in patients in whom posterior fusions ended in the cervical spine versus those in whom the fusion was extended into the thoracic spine. A multicenter retrospective analysis of prospectively followed patients was carried out. A total of 177 adult spine patients undergoing three or more levels of posterior cervical fusions for degenerative disease from January 2008 to May 2013 comprised the patient sample. Cervical lordosis, C2-C7 sagittal plumbline, T1 slope, visual analog scale (VAS), Oswestry Disability Index (ODI), rate of pseudarthrosis, length of hospital stay (LOS), estimated blood loss (EBL), and operating room [OR] time were the outcome measures. We assembled a multicenter (four sites) radiographic and clinical database of patients who had undergone three or more levels of posterior cervical fusions for degenerative disease from January 2008 to May 2013 with at least 2 years of postoperative (post-op) follow-ups. Patients were divided into two groups: Group 1 (fusion ending in the cervical spine) and group 2 (fusion extending into the thoracic spine). All radiographic measurements were performed by an independent experienced clinical researcher. Group 1 and Group 2 had 104 and 73 patients, respectively. Mean EBL for Group 2 was significantly higher than Group 1. Mean OR time and LOS were comparatively higher for Group 2 than Group 1 but were not statistically significant (p>.05). Mean cervical lordosis improved postoperatively in both groups. There were no statistically significant differences in change or maintenance of mean cervical lordosis (2 weeks vs. 2 years post-op) between the two groups (p>.05). Similarly, the change in mean C2-C7 sagittal plumbline and T1 slope was not statistically significantly different between the two groups or with follow-up(p>.05). Clinically, significant improvements in VAS and ODI were noted in both groups from preop to final follow-up, but the difference between groups was not statistically significant. Although the rate of pseudarthrosis was significantly higher in Group 1 (21.2%) than in Group 2 (10.96%), there were no statistically significant differences in adjacent segment degeneration or revision surgery rates between the groups. Both groups had similar clinical and radiographic outcomes. Extension of a posterior cervical fusion into the thoracic spine leads to lower pseudarthrosis rate, whereas stopping in the cervical spine yields lower EBL, OR time, and LOS, demonstrating that there are different benefits for each approach. However, although the optimal end-level remains debatable, there are scenarios in which upper thoracic extension should be considered. At this point, we recommend extension of surgery in smokers and other patients at increased risk for pseudarthrosis as well as in patients with anatomical limitations to strong C7 bone anchorage.


Novel effects of interferon on the brain: microiontophoretic application and single cell recording in the rat.
Interferon (IF), one of the most controversial drugs in cancer therapy, induces a variety of CNS side effects. Therefore, IF was tested on single neuronal activity and compared with other drugs. Recombinant leukocyte A IF, morphine sulfate and L-glutamate were applied microiontophoretically to 18 cortical and 29 thalamic neurons. The majority of the cortical cells were excitated by IF while most of the thalamic cells did not respond to IF; however, morphine and glutamate elicited on these neurons the expected effects. IF produced a long-lasting increase in firing discharges and exhibited dose-response characteristics.


Measuring the effects of genes and environment on complex traits.
Complex diseases and traits are influenced by a combination of genetic and environmental risk factors, some of which may be known, and many of which are unknown. It is possible to estimate the relative importance of the influence of genes and environment on a trait by studying correlations in the trait in related individuals. Known risk factors can be measured and included in the statistical models to understand disease etiology better. The joint effect of specific genes and environmental exposures can be estimated by measuring these in individuals, not necessarily related, with and without the disease of interest or with a range of trait values. These methods are illustrated by considering two example analyses in detail. The first is an analysis of a study of adolescent twins, quantifying the effect of genes and environment, including measured sun exposure, on the density of nevi. The second is an analysis of a case-control study, examining the joint effect of the GSTT1 gene and vegetable intake on risk of colorectal cancer.


Hip joint prosthesis design: effect of stem introducers.
The stress levels in the femoral component of a total hip prosthesis (Corin Taper Fit, Corin Medical Ltd, Cirencester, Gloucestershire, UK) were calculated by finite element (FE) analysis. This prosthesis has two holes drilled in the shoulder to engage a stem introducer. There were no unacceptable stress levels around these holes. Instead the maximum stresses were around the periphery of the shaft of the stem, as has been observed for FE analyses of conventional designs. Three prostheses were also subjected to cyclic mechanical testing (peak load 2.3 kN) according to the appropriate British Standard. The holes were examined for cracks, before and after testing, by stereomicroscopy. All three specimens were able to withstand 5 million loading cycles with no evidence of damage. Thus it is possible to design a femoral component with holes in the shoulder, to accommodate a stem introducer, without creating unacceptable stress concentrations.


Growth and maturation of megakaryocytes is regulated by Lnk/Sh2b3 adaptor protein through crosstalk between cytokine- and integrin-mediated signals.
Various cytokines and growth factors control the differentiation and maturation of megakaryocytes (MKs). However, the mechanism regulating platelet release from MKs is not well understood. Here, we investigated a role of Lnk/Sh2b3, an intracellular adaptor protein, in megakaryopoiesis. Number of MK progenitor in bone marrow (BM) of wild-type or Lnk(-/-) mice and their sensitivity to thrombopoietin (TPO) were determined in colony-forming unit assay. Using BM-derived wild-type or Lnk(-/-) MKs stimulated with TPO, activation of the signaling molecules was biochemically analyzed and effect of integrin stimulation on TPO signals was studied by addition of vascular cell adhesion molecule (VCAM-1). Platelet production from MKs in the presence of VCAM-1 was counted by flow cytometry and their morphological change was observed by time-lapse microscopy. Lnk(-/-) mice showed elevated platelets and mature MKs due to enhanced sensitivity of progenitors to TPO. Erk1/2 phosphorylation induced by TPO was augmented and prolonged in Lnk(-/-) MKs while activation of signal transducers and activators of transcription (Stat)3, Stat5, and Akt was normal. Wild-type MKs, but not in Lnk(-/-) MKs on VCAM-1 showed reduced Stat5 phosphorylation and mitogen-activated protein kinases activation upon stimulation with TPO. Additionally, the presence of VCAM in culture accelerated spontaneous platelet release from mature wild-type MKs, but not from Lnk(-/-) MKs. Results suggest that contact of MKs with adhesion molecules via integrins might contribute to platelet release, which is under Lnk-mediated regulation of Stat-5 activation and show that Lnk functions in responses controlled by cell adhesion and in crosstalk between integrin- and cytokine-mediated signaling.


The role of sphingolipids in the control of skeletal muscle function: a review.
In this review, potential roles for the endogenous sphingolipid, sphingosine, and its derivatives are described for muscle cells. Sphingosine modulates the function of important calcium channels in muscle, including the ryanodine receptor (RyR) calcium release channel of the sarcoplasmic reticulum (SR). Sphingosine blocks calcium release through the SR ryanodine receptor and reduces the activity of single skeletal muscle RyR channels reconstituted into planar lipid bilayers. Sphingosine-blocked calcium release is coincident with the inhibitory effects of sphingosine on [3H]ryanodine binding to the RyR. The sphingomyelin signal transduction pathway has also been identified in both skeletal and cardiac muscle. A neutral form of sphingomyelinase (nSMase) enzyme has been localized to the junctional transverse tubule membrane. The high turnover of the SMase is responsible for the production of ceramide and sphingosine. HPLC analyses indicate that significant resting levels of sphingosine are present in muscle tissue. A model of excitation-contraction coupling is presented suggesting a potential role for this endogenous sphingolipid in normal muscle function. Putative roles for sphingolipid mediators in skeletal muscle dysfunction are also discussed. We hypothesize that sphingosine plays important roles in malignant hyperthermia and during the development of muscle fatigue.


Forearm muscle oxygenation and blood volume parameters during sustained contraction performance in youth sport climbers.
Forearm muscle strength and endurance are essential determinants of sports climbing success. This study aimed to investigate whether delayed rates of muscle oxygen saturation and total hemoglobin correlate to sustained contraction performance of youth climbers. Twelve recreational and competitive youth sport climbers (six females, six males) participated in the study. Variables included finger flexors muscle maximal voluntary contraction, sustained contraction test (SCT), muscle oxygen dynamics (SmO<inf>2</inf>), and blood volume (tHb) parameters. Pearson's correlation coefficients were calculated to determine the correlation between physiological and performance variables. SCT had a significant positive relationship to SmO<inf>2</inf> delayed rate (r=0.728, P=0.007), and a significant negative relationship to tHb delayed rate (r=-0.690, P=0.013). SmO<inf>2</inf> delayed rate and tHb delayed rate also had a significant negative correlation (r=-0.760, P=0.004). According to the results of this study, it can be suggested that delayed rates of SmO<inf>2</inf> and tHb could be used in determining and predicting sustainable finger flexors performance in youth climbers. However, future studies investigating delayed rates of SmO<inf>2</inf> and tHb in climbers of different ability levels are warranted to investigate this issue in more detail.


Giant splenic artery aneurysm.
Giant aneurysms of the splenic artery are uncommon. The mean size of splenic artery aneurysms is reported to be 2.1 cm; they are rarely larger than 3 cm. We present two cases in which the splenic artery aneurysm was larger than 8 cm, discuss the management and operative approach to these infrequently encountered entities, and provide a brief review of the relevant literature.


Evaluation of mycobacillin and versicolin as agricultural fungicides. III. Growth pattern and antibiotic production in soil by Aspergillus versicolor.
Soil supports the growth of a jute pathogen Colletotrichum gloeosporioides but only to a limited extent that of its antagonist Aspergillus versicolor. The growth of the sensitive pathogen is considerably checked by the antagonist in mixed soil culture although versicolin production could not be demonstrated within the limits of assay. Both the sensitive and the antagonistic organisms grow well in soil-compost medium and versicolin production by the latter is also enhanced. The antagonistic effect of Aspergillus versicolor on Colletotrichum gloeosporioides is expectedly more marked in soil-compost medium than in soil medium.


Frequency weighting derived from power absorption of fingers-hand-arm system under z(h)-axis vibration.
The objectives of this study are to derive the frequency weighting from three vibration power absorption (VPA) methods (finger VPA, palm VPA, and total or hand VPA), and to explore whether these energy methods are better than the currently accepted acceleration method. To calculate the VPA weightings, the mechanical impedance of eight subjects exposed to a broadband random vibration spectrum in the z(h)-axis using 18 combinations of hand couplings and applied forces was measured. The VPA weightings were compared with the frequency weighting specified in ISO 5349-1 [2001. Mechanical Vibration--Measurement and Evaluation of Human Exposure to Hand--Transmitted Vibration--Part 1: General Requirements. International Organization for Standardization, Geneva, Switzerland]. This study found that the hand and palm VPA weightings are very similar to the ISO weighting but the finger VPA weighting for the combined grip and push action is much higher than the ISO weighting at frequencies higher than 25 Hz. Therefore, this study predicted that the total power absorption of the entire hand-arm system is likely to be correlated with psychophysical response or subjective sensation. However, if the ISO weighting method cannot yield good predictions of the vibration-induced disorders in the fingers and hand, the hand and palm energy methods are unlikely to yield significantly better predictions. The finger VPA is a vibration measure between unweighted and ISO weighted accelerations. The palm VPA method may have some value for studying the disorders in the wrist-arm system.


Influence of ovariectomy on the canine striated external urethral sphincter (M. urethralis): a stereological analysis of slow and fast twitch fibres.
Slow and fast twitch fibres were stereologically analysed in the morphologically defined and most strongly developed ventral and ventrolateral region of the external urethral sphincter (M. urethralis) using five sexually intact anestrous and five ovariectomized nulliparous beagles. The estimated mean total cross-sectional area of the investigated part of the muscle consisted of 4.2 mm2 (15.1%) type I fibre, 10.0 mm2 (32.1%) type II fibre, and 16.3 mm2 (52.8%) connective tissue in the control group. The corresponding absolute mean value of type I fibres (3.7 mm2/13.5%) was statistically lower in ovariectomized animals. No significant difference between groups was observed in the relative number of transverse profiles of type I and II fibres; type I fibres comprised 23.8% and type II 76.2% of all muscle fibres in the sexually intact group, but 21.8% and 78.2% in the ovariectomy group, respectively. The ovariectomized dogs exhibited a statistically significant lower type I and II fibre number and a concomitant slightly larger mean single profile area (diameter) of fibre type II compared with the control animals. The significantly reduced number and decreased total cross-sectional area of the fatigue-resistant type I fibres in ovariectomized dogs suggest a predominant weakening of the fibre type I portion of the M. urethralis as consequence of ovariectomy. The effect could be mediated by sex hormonal factors and may contribute to the development of postspaying urinary incontinence in female dogs.


Neurolymphomatosis--diagnosis and assessment of treatment response by FDG PET-CT.
Neurolymphomatosis (NL) is lymphomatous infiltration of peripheral nerves, and is an uncommon manifestation of non-Hodgkin's lymphoma (NHL). Although nerve biopsy is the main method for histological diagnosis, a blind nerve biopsy may not be diagnostic. While CT and MRI have been used to detect NL, recent reports demonstrated the benefit of integrated positron emission tomography (PET) using F18-2-fluoro-2-deoxy-D-glucose (FDG) combined with computed tomography (CT). We described the utility of FDG PET-CT in this uncommon subgroup of NHL where it can assist in establishing the diagnosis, the potential to guide sites for biopsy and in the assessment of response to therapy.


Regiospecific 3'-C-prenylation of naringenin by Nocardiopsis gilva prenyltransferase.
The prenylation of flavonoids is a main type of structural modification and can endow flavonoids with greater bioactivity and bioavailability. A soluble prenyltransferase (NgFPT) gene from Nocardiopsis gilva was cloned, expressed and characterized in Escherichia coli. The optimal activity of NgFPT was at pH 7.5 and 30 °C. The activity of NgFPT was significantly enhanced by Ca2+, Al3+, and DMSO. NgFPT showed high selectivity to prenylate flavanones at 3'-C to generate 3'-C-prenyl-flavanones. The Kcat and Km of recombinant NgFPT for naringenin were 0.001 s-1 and 0.045 mM, respectively. Then, recombinant strains were reconstructed by introducing NgFPT gene and the isopentenol utilization pathway. Escherichia coli hosts and fusion tags were screened to improve the yield of 3'-C-prenyl-naringenin in vivo, resulting in maximal 3'-C-prenyl-naringenin production at 3.5 mg/L. By optimizing biotransformation conditions and adopting the resting cell bioconversion, maximum 3'-C-prenyl-naringenin production reached 10.3 mg/L with a specific productivity of 0.21 mg/L/h after 48 h incubation. Thus, the article provides a regiospecific soluble prenyltransferase and a method for the production of 3'-C-prenyl-naringenin by metabolic engineering.


Stronger affinity of reticulocyte release factor than natural suppressor tRNASer for the opal termination codon.
Animal natural suppressor tRNA did not affect the release reaction of reticulocyte release factor (RF) at the same concentration of tRNA (both estimated as being present at a similar level of 3-5 X 10(-8) M in vivo); even at a 10-fold greater concentration the tRNA did not prevent the release reaction with RF. In order to confirm this result, the Ka values were determined. The Ka value between RF and UGA was 1.26 X 10(6) M-1 and that between the suppressor tRNA and UGA amounted to 8 X 10(3) M-1. This result showed that RF had a 150-fold stronger affinity than suppressor tRNA for the opal termination codon. Incorporation of phosphoserine into phosphoprotein via phosphoseryl-tRNA was inhibited by addition of RF to the reaction mixture. These results suggest that animal natural suppressor tRNA in the normal state does not perform its suppressor function, except in special cases where mRNA has the context structure near the opal termination codon (UGA).


Specific characteristics of urethral strictures in a developing country (Brazil).
Evaluate the main etiologies and clinical characteristics of male urethral stricture disease (USD) in Brazil. This multicentric study was performed using retrospective data collected from six Brazilian referral centers of urethral reconstruction. The database comprised data from 899 patients with USD who had undergone surgical treatment from 2008 to 2018. Age, stricture site and primary stricture etiology were identified for each patient. The mean age was 52.13 ± 16.9 years. The most common etiology was iatrogenic (43.4%), followed by idiopathic (21.7%), trauma (21.5%) and inflammatory (13.7%). Of the iatrogenic causes, 59% were secondary to urethral instrumentation (60% by urethral catheterization and 40% by transurethral procedures), 24.8% by other procedures (prostatectomy, radiotherapy, postectomy) and 16.2% by failed hypospadia repairs. Pelvic fracture urethral distraction injuries were responsible for most of the trauma-related strictures (62.7%). When stratified by age, the most common stricture etiology was trauma in the 0-39 years old group (42.8%), idiopathic in the 40-59 years old group (32.4%) and iatrogenic in patients over 60 years old (68%). In regard to the stricture site, 80% presented with an anterior urethral stricture and 20% with a posterior stenosis. In the anterior stenosis group, the most common stricture site was bulbar (39.5%). In Brazil, as in many developed countries, the most common cause of urethral stricture diseases is iatrogenic, especially urethral catheterization. These findings emphasize the need of a careful urethral manipulation and a better training of healthcare professionals. Trauma is still responsible for a great proportion of strictures and inflammatory etiologies are now less frequently observed.


Embryonic cerebellar granule cells are resistant to necrosis induced by homocysteine.
Hyperhomocysteinemia is a risk factor for a range of neurodegenerative conditions, yet its effects in the developing nervous system have been poorly elucidated. We studied the in vitro response of cerebellar granule neurons (CGCs) to homocysteine. We have shown that embryonic CGCs are resistant to homocysteine-induced neurotoxicity, whilst postnatal CGCs are not. This is the first demonstration of a neuronal population undergoing a developmental switch in their response to homocysteine. Greater understanding of this change may have important implications for both neurodegenerative conditions and neurodevelopmental disorders.


Purpura fulminans as a sequel to erythema nodosum in a child with homozygous Leiden mutation and acquired protein S deficiency.
A 6-y-old boy presented with generalized, bruise-like swelling of both legs. Three weeks later, he developed purpura fulminans in one of the affected feet. Histology of the leg swelling was in accordance with erythema nodosum. The boy proved to be homozygous for the Factor V Leiden mutation and to have acquired protein S deficiency. He recovered, with partial loss of two toes. In contrast to what is often stated, erythema nodosum is not always a benign condition. On the basis of this report, we suggest that if extensive erythema nodosum develops in an individual without any known thrombophilic disorder, investigations with respect to the latter should be performed.


Acromegaly secondary to an incidentally discovered growth-hormone-releasing hormone secreting bronchial carcinoid tumour associated to a pituitary incidentaloma.
In this report we emphasize the opportunity of considering the uncommon causes of chronic GH-excess in the initial diagnostic process, such as GHRH hypersecretion, especially in the presence of ambiguous pituitary neuroimaging. This topic may have an important clinical significance in order to plan the most cost-effective diagnostic procedures and management and to avoid unnecessary pituitary neurosurgery.


[Physical measurements of healthy, athletic girls 9-12 years of age in percentile values].
Eight anthropometric data from 550 healthy sporting girls aged 9-12 years are presented as percentiles in tabular form. The results are of importance for the medical practice.


Anemia is related to osteoporosis in Chinese type 2 diabetic patients.
Both anemia and osteoporosis are common in type 2 diabetes mellitus (T2DM). However, the relationship between them remains to be determined. This study showed that anemia was related to osteoporosis in male and female T2DM patients. Diabetes patients with anemia should also be wary of osteoporosis. Anemia and osteoporosis are considered complications of type 2 diabetes mellitus (T2DM). However, the relationship between anemia and osteoporosis in the T2DM population remains to be determined. Thus, we planned the present study to verify their relationship. A retrospective cross-sectional study was performed. The patients were divided into groups according to sex and hemoglobin levels (Q1: ≤ 120, Q2: 120 to ≤ 140, Q3: > 140 in men; Q1: ≤ 110, Q2: 110 to ≤ 130, Q3: > 130 in women). Clinical characteristics and bone mineral density (BMD) were compared. The relationship between anemia and osteoporosis was determined after adjusting for age, diabetic duration, body mass index, alanine aminotransferase, creatinine, HbA1c, and fasting C-peptide. Statistical analysis was performed using SPSS 26.0. This study included 2336 patients (1150 men and 1186 postmenopausal women). The percentage of osteoporosis differed by hemoglobin status in both men (Q1: 20.2%, Q2: 15.5%, Q3: 12.4%, P = 0.031) and women (Q1: 51.4%, Q2: 38.0%, Q3: 34.5%, P < 0.001). Q1, with the lowest hemoglobin level, has higher percentage of osteoporosis in men (20.2%) and in women (51.4%). Hip BMD (men: r = 0.168, P < 0.001, women: r = 0.126, P < 0.001) and femur neck BMD (men: r = 0.150, P < 0.001, women: r = 0.134, P < 0.001) were correlated with hemoglobin levels in both sexes. The odds of osteoporosis increased 1.4-fold in men and 2.0-fold in women in the Q1 groups compared with Q3 groups. Anemia was related to osteoporosis in T2DM patients regardless of sex. Diabetic patients with anemia (men with hemoglobin below 120 g/L and women with hemoglobin below 110 g/L) should also be wary of osteoporosis.


Reduction of treatment volume and radiation doses to surrounding tissues with intraprostatic gold markers in prostate cancer radiotherapy.
High-precision radiotherapy with gold marker implantation is a standard technique for prostate cancer treatment. To provide insight into the beneficial effect of gold markers, the influence on treatment volume and radiation doses to healthy tissues was investigated. Three consecutive treatment margins were constructed, for 10 patients with localized prostate cancer, to show the reduction of planning target volume (PTV): PTV 10 mm (no markers), PTV 7 mm (markers), and PTV 7/5 mm (markers and online correction). On planning computed tomography (CT) scan, the prostate, bladder, rectal wall, and anal canal were contoured. The treatment volume and radiation doses to surrounding organs were calculated. In 65 patients, with the online protocol and gold markers, late toxicity was evaluated. With gold markers a significant PTV reduction of 27% was achieved (P < .001). Subsequently, radiation dose reductions to the mean of 17% (± 4.5%) to the bladder, 19% (± 4.7%) to the anal canal, and 12% (± 3%) to the rectal wall, respectively were seen (P < .001). With 5-mm posterior margins an additional PTV reduction of 3.7% (P < .001) and total radiation dose reduction to the mean of 24% (± 4%), and 16% (± 4.5%) to anal canal and rectal wall, respectively were seen (P < .001). Late Grade 1-2 genitourinary and gastrointestinal toxicity was seen in 32%, and 33%, respectively. Grade 3 toxicity was less than 10%. This study showed a significant reduction of treatment volume and radiation doses to healthy tissues with intraprostatic gold markers.


Recessive NUP54 Variants Underlie Early-Onset Dystonia with Striatal Lesions.
Infantile striatonigral degeneration is caused by a homozygous variant of the nuclear-pore complex (NPC) gene NUP62, involved in nucleo-cytoplasmic trafficking. By querying sequencing-datasets of patients with dystonia and/or Leigh(-like) syndromes, we identified 3 unrelated individuals with biallelic variants in NUP54. All variants clustered in the C-terminal protein region that interacts with NUP62. Associated phenotypes were similar to those of NUP62-related disease, including early-onset dystonia with dysphagia, choreoathetosis, and T2-hyperintense lesions in striatum. In silico and protein-biochemical studies gave further evidence for the argument that the variants were pathogenic. We expand the spectrum of NPC component-associated dystonic conditions with localized basal-ganglia abnormalities. ANN NEUROL 2023;93:330-335.


2-(N-Benzyl-N-phenylsulfonamido)alkyl amide derivatives as γ-secretase inhibitors.
A series of (N-benzyl-N-phenylsulfonamido)alkyl amides were developed from classic and parallel synthesis strategies. Compounds with good in vitro and in vivo γ-secretase activity were identified and described.


Utilization and success rates of unstimulated in vitro fertilization in the United States: an analysis of the Society for Assisted Reproductive Technology database.
To examine the utilization and outcomes of natural cycle (unstimulated) IVF as reported to the Society of Assisted Reproductive Technology (SART) in 2006 and 2007. Retrospective analysis. Dataset analysis from the SART Clinical Outcome Reporting System national database. All patients undergoing IVF as reported to SART in 2006 and 2007. None. Utilization of unstimulated IVF; description of patient demographics; and comparison of implantation and pregnancy rates between unstimulated and stimulated IVF cycles. During 2006 and 2007 a total of 795 unstimulated IVF cycles were initiated. Success rates were age dependent, with patients <35 years of age demonstrating clinical pregnancy rates per cycle start, retrieval, and transfer of 19.2%, 26.8%, and 35.9%, respectively. Implantation rates were statistically higher for unstimulated compared with stimulated IVF in patients who were 35 to 42 years old. Unstimulated IVF represents <1% of the total IVF cycles initiated in the United States. The pregnancy and live birth rates per initiated cycle were 19.2% and 15.2%, respectively, in patients <35 years old. The implantation rates in unstimulated IVF cycles compared favorably to stimulated IVF. Natural cycle IVF may be considered in a wide range of patients as an alternative therapy for the infertile couple.


Reovirus sigma1 fiber incorporated into adenovirus serotype 5 enhances infectivity via a CAR-independent pathway.
Adenovirus serotype 5 (Ad5) has been used for gene therapy with limited success because of insufficient infectivity in cells with low expression of the primary receptor, the coxsackie and adenovirus receptor (CAR). To enhance infectivity in tissues with low CAR expression, tropism expansion is required via non-CAR pathways. Serotype 3 Dearing reovirus utilizes a fiber-like sigma1 protein to infect cells expressing sialic acid and junction adhesion molecule 1 (JAM1). We hypothesized that replacement of the Ad5 fiber with sigma1 would result in an Ad5 vector with CAR-independent tropism. We therefore constructed a fiber mosaic Ad5 vector, designated as Ad5-sigma1, encoding two fibers: the sigma1 and the wild-type Ad5 fiber. Functionally, Ad5-sigma1 utilized CAR, sialic acid, and JAM1 for cell transduction and achieved maximum infectivity enhancement in cells with or without CAR. Thus, we have developed a new type of Ad5 vector with expanded tropism, possessing fibers from Ad5 and reovirus, that exhibits enhanced infectivity via CAR-independent pathway(s).


Spatial and temporal variation in size of polar bear (Ursus maritimus) sexual organs and its use in pollution and climate change studies.
Sexual organs and their development are susceptible to atmospheric transported environmental xenoendocrine pollutants and climate change (food availability). We therefore investigated sexual organs from 55 male and 44 female East Greenland polar bears (Ursus maritimus) to obtain information about growth/size and sexual maturity. Then, the genitalia size was compared with those previously reported from Canadian and Svalbard polar bears. Growth models showed that East Greenland male polar bears reached sexual maturity around 7 years of age and females around 4 years of age. When comparing East Greenland and Svalbard polar bears, the size of baculum and uterus were significantly lower in the East Greenland polar bears (ANOVA: all p < 0.05). Based on previously published baculum mean values from Canadian polar bears, a similar baculum pattern was found for East Greenland vs. Canadian polar bears. It is speculated whether this could be a result of the general high variation in polar bear body size, temporal distribution patterns of anthropogenic long-range transported persistent organic pollutants or climate change (decreasing food availability). The present investigation represents conservation and background data for future spatial and temporal assessments of hunting, pollution and climate change scenarios.


Genome analysis of Ranavirus frog virus 3 isolated from American Bullfrog (Lithobates catesbeianus) in South America.
Ranaviruses (family Iridoviridae) cause important diseases in cold-blooded vertebrates. In addition, some occurrences indicate that, in this genus, the same virus can infect animals from different taxonomic groups. A strain isolated from a Ranavirus outbreak (2012) in the state of Sao Paulo, Brazil, had its genome sequenced and presented 99.26% and 36.85% identity with samples of Frog virus 3 (FV3) and Singapore grouper iridovirus (SGIV) ranaviruses, respectively. Eight potential recombination events among the analyzed sample and reference FV3 samples were identified, including a recombination with Bohle iridovirus (BIV) sample from Oceania. The analyzed sample presented several rearrangements compared to FV3 reference samples from North America and European continent. We report for the first time the complete genome of Ranavirus FV3 isolated from South America, these results contribute to a greater knowledge related to evolutionary events of potentially lethal infectious agent for cold-blooded animals.


Foam at inner eye canthus in office workers, compared with an average Danish population as control group.
Foam formation in the eye canthus is well-known. The presence of foam was observed in 169 office workers in 4 town halls in Copenhagen County compared with 112 control persons from the general population in the same area. The presence of foam depends on age and gender. A significant increase with age was observed in the control population (P = 0.0078). In both groups, females had a significantly lower occurrence of foam than males (P = 0.0043, P = 0.010). This difference was mainly caused by the use of eye make-up. After correction for age, gender and use of eye make-up, the prevalence of foam was significantly lower in the office population than in the control population (P less than 0.0001). Furthermore, low foam formation was significantly correlated to reported subjective eye irritation in the office population (P = 0.0074), but not in the control population (P = 0.40). Also, significant positive correlation between absence of foam and different degrees of dry eyes (expressed as a combination of premature break-up of the precorneal tearfilm and lissamine green stained epithelial damage of the bulbar conjunctiva) was found both in the office population and in the control population (P = 0.0090, P = 0.0034). However, after correction for the more frequent appearance of dry eyes in the office population, foam was still observed significantly less frequently in the office population than in the control population (P = 0.0001). It is concluded that the decreased foam formation in the office worker constitutes a key symptom in the development of 'office eye syndrome'. In what way the office environment influences the foam formation is unknown. Possible mechanisms are discussed.


[Breast reconstruction by prosthesis].
Breast reconstruction by prosthesis remains the most used in the world and even tends to increase again at the expense of musculo-cutaneous flaps since the systematic use, in recent years, of adipocytes grafts (lipofilling) before and/or after in place of the implant. This simpler technique is often preferred by patients who want to avoid scars and pain away from the chest area. The use of different implant forms, fat injection, abdominal advancement flaps, biological or synthetic matrices can significantly improve the results of these reconstructions in secondary or immediate. All these techniques are detailed in the following article to show the different devices that allow to achieve this intervention with maximum security.


Recent global trends in testicular cancer incidence and mortality.
Testicular cancer (TCa) has a relatively rare incidence and mortality, but has not been thoroughly evaluated. We analyzed global variations and recent trends in TCa incidence and mortality.Age-standardized rates (ASRs) of TCa incidence and mortality were retrieved from the GLOBOCAN 2012 database. Temporal patterns were assessed using data obtained from the Cancer Incidence in Five Continents (volumes I-X) and World Health Organization Mortality databases. The incidence and mortality trends over the last 10 years were analyzed using join point analysis.Western and Northern Europe had the highest incidence of TCa (ASR = 8.7 and 7.2, respectively), with most countries showing an increase in incidence rates except for China, which had a stable incidence. Incidence rates were markedly increased in Southern European countries (average annual percent change of 6.8% in Croatia and 6.1% in Spain) but were attenuated in western Europe. The highest mortality rates were observed in western Asia (ASR = 0.7), with most countries showing a decrease in mortality.While the incidence of TCa has increased, mortality from TCa has decreased in most countries. More socioeconomically developed countries had a higher incidence of TCa with lower mortality.


The contributions of value-based decision-making and attentional bias to alcohol-seeking following devaluation.
To investigate the mediating role of attentional bias for alcohol cues on alcohol-seeking following devaluation of alcohol. Between subject. Eye-tracking laboratory at the University of Liverpool. Student social drinkers (n = 64). An operant choice task in which participants chose between simultaneously presented alcohol and non-alcohol drink rewards, while attentional bias for alcohol and non-alcohol drink cues was inferred from eye movements. Participants then consumed 30 mL of an alcoholic beverage, which was either presented alone (no devaluation: n = 32) or had been adulterated to taste unpleasant (devaluation: n = 32). Choice and attentional bias for the alcohol and non-alcohol drink pictures were then measured again. Alcohol devaluation reduced behavioural choice for alcohol (F = 32.64, P < 0.001) and attentional bias for the alcohol pictures indexed by dwell time (F = 22.68, P < 0.001), initial fixation (F = 7.08, P = 0.01) and final fixation (F = 22.44, P < 0.001). Mediation analysis revealed that attentional bias partially mediated the effect of devaluation on alcohol choice; however, the proportion of the variance accounted for by attentional bias is low to moderate (~30%). Among student social drinkers, attentional bias is only a partial mediator of alcohol choice following devaluation of alcohol. Value-based decision-making may be a more important determinant of drinking behaviour among student social drinkers than attentional bias.


Predictive modelling of cervical disc implant wear.
This study presents a chain of simulations aimed at estimating the wear in a cervical disc implant and providing insight into the in vivo biomechanical performance of the implant. The simulation chain can start with determining a representative maximum range of motion (ROM) of a person's head. The ROM is used as motion input to a kinematic simulation of the cervical spine containing a disc implant. The cervical spine geometry is obtained from computed tomography (CT) scans and converted to STL format using reverse engineering software. The time histories of the loads imposed by the adjacent vertebrae on the implant, as well as the vertebral relative rotations can be extracted from the kinematic simulation. Alternatively, force and motion profiles prescribed by wear test protocols (e.g. ISO 18192-1 and ASTM F2423-05) can be used. The force and motion profiles are applied as boundary conditions to a non-linear finite element model (FEM) of the implant to determine the time-varying contact stress and slip velocity distributions at the interface between the two halves of the implant. The stresses and slip velocities are used in a linear wear model to estimate the wear rate distribution at the FEM's nodal points where contact occurs. Reverse engineering software is used to triangulate the contact surface so that the total wear volume can be calculated. The simulation chain's predicted wear rate shows good agreement with in vitro results in the literature. The simulation chain is thereby demonstrated to be suitable for comparative pre-experimental studies of spinal implant designs.


A scaffold laden with mesenchymal stem cell-derived exosomes for promoting endometrium regeneration and fertility restoration through macrophage immunomodulation.
Endometrial traumas may cause intrauterine adhesions (IUAs), leading to infertility. Conventional methods in clinic have not solved the problem of endometrial regeneration in severe cases. Umbilical cord-derived mesenchymal stem cell (UC-MSC)-based therapies have shown some promising achievements in the treatment of IUAs. However, the limitations of potential tumorigenicity, low infusion and low retention are still controversial and restricted the clinical application of MSCs. In contrast, UC-MSC-derived exosomes exhibit a similar function to their source cells and are expected to overcome these limitations. Therefore, a novel and viable cell-free therapeutic strategy by UC-MSC-derived exosomes was proposed in this study. Here, we designed a construct of exosomes and collagen scaffold (CS/Exos) for endometrial regeneration in a rat endometrium-damage model, and investigated the regeneration mechanism through macrophage immunomodulation. The CS/Exos transplantation potently induced (i) endometrium regeneration, (ii) collagen remodeling, (iii) increased the expression of the estrogen receptor α/progesterone receptor, and (iv) restored fertility. Mechanistically, CS/Exos facilitated CD163+ M2 macrophage polarization, reduced inflammation, and increased anti-inflammatory responses in vivo and in vitro. By RNA-seq, miRNAs enriched in exosomes were the main mediator for exosomes-induced macrophage polarization. Overall, we demonstrated that CS/Exos treatment facilitated endometrium regeneration and fertility restoration by immunomodulatory functions of miRNAs. Our research highlights the therapeutic prospects of CS/Exos for the management of IUAs. STATEMENT OF SIGNIFICANCE: Severe endometrial traumas always result in intrauterine adhesions (IUAs) and infertility. The limited outcomes by conventional methods in the clinic make it very important to develop new strategies for endometrium regeneration and fertility restoration. In this study, an exosome-laden scaffold (CS/Exos) was designed and the transplantation of CS/Exos potently induced (i) endometrium regeneration, (ii) collagen remodeling, (iii) increased the expression of the estrogen receptor α/progesterone receptor, and (iv) restored fertility. In mechanism, the construct of CS/Exos facilitated M2 macrophage polarization, reduced inflammation, and increased anti-inflammatory responses. Furthermore, miRNAs enriched in exosomes were the main mediator for exosome-induced macrophage polarization. This study highlights the therapeutic prospects of CS/Exos and the translational application for the management of severe IUAs.


Protease inhibitor monotherapy is effective in controlling human immunodeficiency virus 1 shedding in the male genital tract.
Cross-sectional study comparing seminal human immunodeficiency virus type 1 (HIV-1) shedding in patients receiving boosted protease inhibitor monotherapy (mtPI/rtv) (n = 66) versus triple therapy (TT) (n = 61). Seminal HIV-1 shedding rates in patients with undetectable plasma HIV-RNA were 16.0% on mtPI/rtv compared with 28.6% on TT (p 0.173). Aviraemic status and time on viral suppression were independently associated with lack of seminal HIV-1 shedding. During TT, non PI/rtv-based regimens were associated with a better control of HIV infection in semen despite similar time on viral suppression. The use of mtPI/rtv in well-controlled patients is not associated with increased seminal HIV excretion compared with TT.


Antibacterial activity of cefotaxime, desacetylcefotaxime, and the combination of the two.
Cefotaxime (CTX) is metabolized to desacetylcefotaxime (dCTX), which is antibacterially active. The combination of CTX and dCTX is synergistic in a 1:1 ratio, but in this study, a combination of CTX:dCTX in a fixed ratio of 5:1 was not found synergistic when tested on 120 recently isolated clinical strains. Zone diameters of disks containing pure CTX or dCTX 30 micrograms or the combination of CTX/dCTX in micrograms: 25/5, 20/10, 15/15, and 10/20, were compared. The correlation between the zone size of the pure CTX disk and the 25/5, 20/10, and 15/15 disks were high with correlation coefficients (r) 0.98 to 0.96. Regardless of the metabolism and the potential synergy, no differences were found in the zone sizes comparing the pure CTX disk with the combination with a ratio from 5:1 to 1:1. The clinical microbiological laboratory can go on using the pure 30 micrograms CTX disk for routine susceptibility testing.


The toxic shock syndrome in a burn victim.
A case of toxic shock syndrome (TSS) in a 6-year-old boy with a 5 per cent body surface area partial thickness scald burn is reported. Biobrane was the wound dressing used initially. The clinical and laboratory characteristics of the syndrome are listed. The syndrome is caused by an exotoxin of Staph. aureus and can occur in the absence of invasive infection. The syndrome, first described in menstruating women who used tampons, has occurred in patients with a variety of wounds. Reports of the TSS syndrome in burn victims are limited to children whose wounds were covered. Children are most vulnerable to the development of TSS because of their limited prior exposure to the toxin.


Comparison of Adult and Pediatric Cochlear Implant Wound Complications: A Meta-Analysis.
To compare age-related differences in wound complications following cochlear implantation (CI). We performed a systematic review of PubMed, Cochrane Database, and Web of Science databases to identify original research evaluating the patient-level factors (demographics and medical history) associated with wound complications following CI. Outcomes were expressed as relative risk (RR) with 95% confidence intervals using the inverse variance method. Studies without comparison groups were described qualitatively. Thirty-eight studies representing 21,838 cochlear implantations were included. The rate of wound complications ranges from 0% to 22%. Patient age (adult versus pediatric) was the only factor with comparison groups appropriate for meta-analysis. The 10 studies (n = 9547 CI's) included in the meta-analysis demonstrated that adults had a higher incidence of overall wound complications (2.94%) than in children (2.44%) (RR 1.31, 95% CI 1.01-1.69). Adults had a higher incidence of general/unclassified wound complications (2.07%) than in children (1.34%) (RR 1.68, 95% CI 1.12-2.52). There was no difference between adults and children for specific complications such as hematoma, infection, or seroma. Elderly patients (over age 75) have wound complication rates that range from 1% to 4%. No studies contained comparison groups regarding other patient-level factors and CI wound complications. CI wound complication rates reported in the literature are low; however, adults have a higher risk of these complications than pediatric patients. The reported complication rate in elderly adults is low. There is a gap in CI research in consistently reporting wound complications and rigorous research investigating the impact of patient-level factors and wound complications. NA Laryngoscope, 133:218-226, 2023.


The effect of orthotics on intersegmental foot kinematics and the EMG activity of select lower leg muscles.
Persons with exertional related leg pain are managed using orthoses. This study aimed to determine the effectiveness of two orthoses in altering foot motion and muscle activity in symptomatic individuals. 52 subjects with lower extremity pain complaints of a non-traumatic, mechanical origin received one of two orthoses. Foot kinematics and EMG activity were recorded while treadmill walking in 3 footwear conditions. The peak EMG activity of the sandal and sandal orthotic trials (normalized to peak barefoot values) and foot motion during 4 subphases of stance were obtained. Using a multivariate multilevel model via linear mixed models, the effect of orthoses within these phases on motion and EMG was determined. An effect of orthotic type was not present for any of the rearfoot or forefoot motions (p>.10). A significant effect of footwear and orthotic type on first ray motion (p<.05) during subphases 2 and 4 was seen. During subphase 4 an interaction effect between footwear condition and orthotic type on tibialis posterior EMG activity (p=.036) was present. Orthoses are unable to control rear or midfoot motion but appear to control first ray motion and during late stance, affect tibialis posterior muscle activity. Public trials registry number: NCRT02143947.


Substance P: localization, concentration and release in cerebral arteries, choroid plexus and dura mater.
Substance P-like immunoreactivity (SPLI) was studied by immunocytochemistry and radioimmunoassay in the cerebral arteries, choroid plexus and dura mater of the guinea-pig, rabbit, cat and man. The highest concentrations were found in cerebral blood vessels: 6.1 +/- 2.3 pmol/g (guinea-pig), 9.0 +/- 1.1 pmol/g (rabbit), 7.1 +/- 0.4 pmol/g (cat), and 2.4 +/- 0.9 pmol/g (man). Lower levels were obtained in the choroid plexus and dura mater. The distribution of substance P (SP)-immunoreactive nerve fibres found in various regions of the guinea-pig correlated well with the amount of SPLI measured. Sympathectomy did not alter the concentration of SPLI in the dura mater or in cerebral blood vessels. Electrical field stimulation or 124 mM potassium enhanced the spontaneous efflux of SPLI by 10 and 20%, respectively, from superfused pial arteries in vitro. These data are in support of a functional role of perivascular SP within the cranial circulation.


The α7 and β2 nicotinic acetylcholine receptor subunits regulate apoptosis in the infant hippocampus, and in sudden infant death syndrome (SIDS).
Apoptosis is increased in the hippocampus of infants who died of sudden infant death syndrome (SIDS), yet it is not known via which mechanism this has occurred. Following existing support for a role of the α7 and β2 nicotinic acetylcholine receptor (nAChR) subunits in apoptotic regulation, we aimed to determine whether these subunits are altered in the SIDS hippocampus and if they are correlated with cell death markers of active caspase-3 (Casp-3) and TUNEL. Further analyses were run according to the presence of major SIDS risk factors related to hypoxia (bed-sharing and prone sleeping), infection (presence of an upper respiratory tract infection (URTI)), cigarette smoke exposure and gender. Immunohistochemical expression of the markers was studied in 4 regions of the hippocampus (Cornu Ammonis (CA)1, CA2, CA3, CA4) and subiculum amongst 52 infants (aged 1-7 months) who died suddenly and unexpectedly (SUDI) and for whom the cause of death was explained (eSUDI; n = 9), or not and characterised as SIDS I (n = 8) and SIDS II (n = 35) according to the San Diego diagnostic criteria. Results showed that SIDS II infants had widespread increases in TUNEL compared with eSUDI and SIDS I infants, as well as increased α7 and Casp-3 in CA2 compared to eSUDI infants, although these changes were predominant amongst infants who did not bed-share. Cigarette smoke exposure had minimal effects on the markers, while an URTI was associated with changes in all markers (after accounting for bed-sharing). Our findings support the role of nAChRs in regulating apoptosis in the SIDS hippocampus, and highlight the need for separate analysis according to risk factors.


The sorption of heavy metal species by sediments in soakaways receiving urban road runoff.
Infiltration facilities are designed for both the retention of non-point pollutants and the replenishment of groundwater in urban areas. In this study, sorption tests were conducted to evaluate the speciation of heavy metals and their behaviour in infiltration facilities receiving urban road runoff containing high DOC concentrations and stable heavy metal organic complexes. Road dust and three soakaway sediments were collected from heavy traffic areas and a residential area with an infiltration-type sewage system in Tokyo, Japan. Sequential multiple batch tests were conducted by adding prepared road dust leachate (artificial road runoff) or deionised water to soakaway sediment to obtain soakaway sediment leachate (artificial percolating water from soakaway sediment), which mimicked the sorption by sediments in soakaways receiving urban road runoff. Heavy metal speciation was assessed by means of a combination of anion-exchange resin measurements and MINTEQA2 model calculations, and further validated by chelating resin measurements. In road dust leachates and soakaway sediment leachates, Cu predominantly existed as organic complexes and carbonates, whereas most Mn, Zn and Cd were found to exist in the form of free ions and carbonate complexes. Stable organic complexes of Cu in road dust leachates were strongly adsorbed by soakaway sediments despite the limited adsorption of DOC. On the other hand, desorption of free Mn, Zn and Cd ions from the sediment receiving road dust leachates was observed, indicating that heavy metals such as Mn, Zn and Cd may ultimately reach groundwater as free ions.


Workplace Social Support and Work Engagement Among Japanese Workers: A Nationwide Cross-sectional Study.
We investigated the relationship between employees' perceptions of the number of sources of workplace social support and work engagement and whether each type of workplace social support is independently related to work engagement. A cross-sectional study was conducted using a questionnaire survey in Japan. In total, 12,017 participants were analyzed. Participants were asked about 4 sources of workplace social support: supervisors, colleagues/subordinates, occupational health staff, and external counselors contracted by the workplace. Work engagement was measured using the 9-item Utrecht Work Engagement Scale. Coefficients were estimated using multiple regression analyses. The coefficient of work engagement increased as the number of sources of perceived workplace social support increased. Each support was also positively related to work engagement. Organizations should develop systems comprising various sources of workplace social support to increase employee work engagement.


Long-term exposure to ELF-MF ameliorates cognitive deficits and attenuates tau hyperphosphorylation in 3xTg AD mice.
Although numerous studies have reported the influence of extremely low frequency magnetic field (ELF-MF) exposure on human health, its effects on cognitive deficits in Alzheimer's disease (AD) have remained under debate. Moreover, the influence of ELF-MF on hyperphosphorylated tau, which is one of the most common pathological hallmarks of AD, has not been reported to date. Therefore, transgenic mice (3xTg) were used in the present study. 3xTg mice, which express an APP/PS1 mutation combined with a tau (P301L) mutation and that develop cognitive deficits at 6 months of age, were subjected to ELF-MF (50Hz, 500μT) exposure or sham exposure daily for 3 months. We discovered that ELF-MF exposure ameliorated cognitive deficits and increased synaptic proteins in 3xTg mice. The protective effects of ELF-MF exposure may have also been caused by the inhibition of apoptosis and/or decreased oxidative stress levels that were observed in the hippocampus tissues of treated mice. Furthermore, tau hyperphosphorylation was decreased in vivo because of ELF-MF exposure, and this decrease was induced by the inhibition of GSK3β and CDK5 activities and activation of PP2Ac. We are the first to report that exposure to ELF-MF can attenuate tau phosphorylation. These findings suggest that ELF-MF exposure could act as a valid therapeutic strategy for ameliorating cognitive deficits and attenuating tau hyperphosphorylation in AD.


[Apparent life-threatening events due to cow's milk allergy in infants].
The analysis of an apparent life-threatening event is mainly based on the clinical approach. When the event occurs after a meal, the diagnosis of acid gastroesophageal reflux complicated by esophagitis is suspected first. Cow's milk protein allergy is suspected when the event occurs during weaning from breastfeeding or when it is accompanied by urticaria or relapses when cow's milk is reintroduced. We report on two cases of an apparent life-threatening event associated with cow's milk protein allergy, whose symptoms and first diagnostic approach initially delayed diagnosis. Clinical manifestations of food allergy need to be known in order to avoid errors in diagnostic orientation and therapy, which may be responsible for more severe recurrences.


Incidence and risk of developing rheumatic diseases in 19,724 patients with palindromic rheumatism in South Korea: A nationwide population-based study.
The spectrum of progression of palindromic rheumatism (PR) to chronic diseases is quite variable. Hence, this study aimed to investigate the incidence and risk of developing rheumatic diseases in PR using nationwide, population-based medical claims data from Korea. We assessed the incidence rate (IR) of PR in the population in the given year. After matching individuals with PR with those without PR (1:10) for age, gender, and the index year, we calculated the hazard ratios (HRs) with 95% confidence intervals (CIs) using the Cox proportional hazard model. A total of 19,724 newly diagnosed incident PR cases were identified from 2010 to 2016. The mean age was 50.2±14.9 years. The incidence of PR was 7.02 (95% CI 6.92-7.12) per 100,000 person-years (6.22 and 7.80 in men and women, respectively). During observation, 8.79% patients with PR and 0.30% individuals without PR developed various outcome diseases. Patients with PR had an increased risk of seropositive rheumatoid arthritis (HR 46.51, 95% CI [41.05-52.69]), psoriatic arthritis (44.79 [15.16-132.35]), systemic lupus erythematosus (24.53 [16.15-37.24]), mixed connective tissue disease (22.01 [7.65-63.34]), Behçet's disease (21.04 [13.81-32.06]), Sjögren's syndrome (12.36 [8.54-17.88]), ankylosing spondylitis (9.00 [6.67-12.15]), dermatomyositis/polymyositis (6.14 [2.55-14.82]), and systemic sclerosis (3.75 [1.47-9.58]) compared with individuals without PR. This nationwide, population-based cohort study demonstrated that about one-eleventh of patients with PR eventually develop systemic rheumatic diseases and that patients with PR have an increased risk of developing various rheumatic diseases including seropositive rheumatoid arthritis.


Degradation of sperm histones in vitro by cytoplasm of the sea urchin egg.
Sperm-specific histone variants in the sea urchin Paracentrotus lividus are replaced early after fertilization with a specific embryonic set of histone variants. A possible in vitro model for the involvement of a degradation mechanism in the replacement of sperm-specific histones is presented. Soluble sperm histones are shown to be degraded quickly by egg cytoplasm. The proteolytic activity is maximal at pH 3.0; H1 and H2A histones are the most sensitive while H3 and H4 are the most resistant. H2B histones have an intermediate sensitivity. Histone degradation by egg cytoplasm or by purified fractions of it can be inhibited by chymostatin and leupeptin and, to a lesser degree, by pepstatin.


Current pain and fear of pain contribute to reduced maximum voluntary contraction of neck muscles in patients with chronic neck pain.
To assess a range of physical and psychological factors and determine which factors contribute the most to reduced strength in patients with neck pain. Regression. Laboratory. Women with chronic neck pain (n=34) and healthy controls (n=14). Not applicable. Neck flexion, extension, and lateral flexion maximum voluntary contractions (MVC) were measured in patients and healthy controls. Additional parameters were collected for the patient group including: (1) questionnaires measuring general health (Medical Outcomes Study 36-Item Short-Form Health Survey), pain intensity, disability (Neck Disability Index [NDI]; Patient Specific Functional Scale), and fear of movement (Fear-Avoidance Beliefs Questionnaire [FABQ]), (2) pressure pain thresholds, (3) cross-sectional area of selected neck muscles, and (4) surface electromyography from selected neck muscles during a multidirectional isometric task. Univariate and multivariate regression analyses were applied with the average MVC (average of flexion, extension, and lateral flexion MVC) as the dependent variable. The average MVC was significantly lower in patients (mean ± SD, 130.0±6.0N) compared with controls (166.9±11.7N; P<.01). Univariate regression of the average MVC with the FABQ, NDI, or pain experienced during the MVC gave R(2) values of 13.4%, 13.8%, and 21.1%, respectively. Collectively, the FABQ and pain experienced during the MVCs resulted in an R(2) of 26.6% and the FABQ, contraction pain, and NDI, an R(2) of 28.2%. The average maximum voluntary force produced in neck flexion, extension, and lateral flexion is inversely and moderately correlated with the pain experienced during maximal contraction, fear of movement, and aspects of neck disability in patients with chronic neck pain.


Anxiety among medical students and junior doctors in Denmark.
International studies document that medical education and the transition from student to medical doctor may be a stressful and difficult time. High anxiety levels impact professional performance and quality of life. The aim of this study was to investigate the prevalence of anxiety among Danish final-semester medical students and newly graduated medical doctors, including individual changes. This was a descriptive cohort and cross-sectional study based on a questionnaire given to medical students and newly graduated doctors between December 2020 and May 2021. The survey used the following validated anxiety scales: the Leeds Self-assessment of Anxiety scale and the State-Trait Anxiety Inventory. The data were analysed for medical students and doctors as cross-sectional analyses. A total of 175 medical students and 65 newly graduated doctors were included; 20 participated in both surveys. We found that 54 (32.5%) of the medical students and 12 (19.4%) of the newly graduated doctors scored pathologically anxious (p = 0.06). The measured anxiety level was higher than the anxiety level found in the background populations from other studies. Anxiety was related to gender and to previous treatment for stress or anxiety and it persisted from student life into life as a young doctor. A high proportion of the medical students reported anxiety, a condition which remained among the young doctors. The Emergency Medicine Research Unit, Odense University Hospital, Denmark. not relevant.


Combining fractional carbon-dioxide laser resurfacing with face-lift surgery.
The human face ages in three different ways: tissues descend; the skin develops rhytides, dyschromia, and numerous lesions; and facial volume is lost. Face-lift surgery and skin resurfacing are two of the mainstays of facial rejuvenation. Today, carbon-dioxide laser resurfacing is, arguably, the gold standard for resurfacing the skin. This article describes the rationale and application of simultaneous fractional laser resurfacing with face-lift surgery. The discussion includes the author's technique, preoperative and postoperative regimens, and experience.


Analyzing the water budget and hydrological characteristics and responses to land use in a monsoonal climate river basin in South China.
Hydrological models have been increasingly used by hydrologists and water resource managers to understand natural processes and human activities that affect watersheds. In this study, we use the physically based model, Soil and Water Assessment Tool (SWAT), to investigate the hydrological processes in the East River Basin in South China, a coastal area dominated by monsoonal climate. The SWAT model was calibrated using 8-year (1973-1980) record of the daily streamflow at the basin outlet (Boluo station), and then validated using data collected during the subsequent 8 years (1981-1988). Statistical evaluation shows that SWAT can consistently simulate the streamflow of the East River with monthly Nash-Sutcliffe efficiencies of 0.93 for calibration and 0.90 for validation at the Boluo station. We analyzed the model simulations with calibrated parameters, presented the spatiotemporal distribution of the key hydrological components, and quantified their responses to different land uses. Watershed managers can use the results of this study to understand hydrological features and evaluate water resources of the East River in terms of sustainable development and effective management.


A review of reports on single-incision laparoscopic surgery for Crohn's disease.
The aim of this review was to analyze the currently available literature on single-incision laparoscopic surgery (SILS) for Crohn's disease (CD) with respect to surgical indications, surgical techniques, feasibility, and possible benefits of SILS for CD. A systematic query of articles published from January 2010 to July 2018 was performed. The studies were assessed for patient's age, gender, body mass index, disease type, SILS procedure, surgical procedure, incision length, operation time, rates of conversion to open surgery, postoperative complications, mortality, length of hospital stay, and rates of reoperation. After an initial review, 11 reports were selected. The surgical techniques and instruments showed wide variation. The mean operation time for SILS tended to be shorter than that for multiport laparoscopic surgery (MLS). The reported rates of conversion to open surgery and postoperative complications were not very different from those reported for MLS. In conclusion, the present review suggests that the SILS technique may be feasible and safe for select patients with CD. However, because we reviewed only a few studies with small sample sizes, prospectively designed trials with a large number of patients are required to clarify the true benefits of SILS for CD.


Phytochemistry, antioxidant, anticancer, and acute toxicity of traditional medicinal food Biarum bovei (Kardeh).
The Biarum species (Kardeh) has been consumed as a traditional functional food and medicine for decades. The current study investigates the phytochemistry, in-vitro and in-vivo bioactivities of methanol extracts of B. bovei. The Gas-chromatography mass spectrophotometer (GS/GS-MS) was used to analyze the phytochemical profile of the methanol extracts of B. bovei leaves and corms. The B. bovei extracts (BBE) were also investigated for in-vitro antioxidant, anticancer, and in-vivo acute toxicity (2000 mg/kg) activities. The chemical profiling of BBE revealed mainly fatty acids, phytosterol, alcohols, and hydrocarbon compounds. Namely, Linoleic acid, eliadic acid, palmitic acid, 22,23-dihydro-stigmasterol, and campesterol. The antioxidant activity of BBE ranged between 0.24-3.85 μg TE/mL based on different assays. The extracts also exhibited significant anticancer activity against DU-145 (prostate cancer cells), MCF-7 (human breast adenocarcinoma), and HeLa (human cervical cancer) cell lines with IC50 values ranging between 22.73-44.24 μg/mL. Rats fed on 2000 mg/kg dosage of BBE showed absence of any toxicological sign or serum biochemical changes. The detected phytochemicals and bioactivities of BBE scientifically backup the folkloric usage as an important source of nutraceuticals and alternative medicine for oxidative stress-related diseases and carcinogenesis inhibition.


Accommodative microfluctuations and pupil diameter.
The nominally steady-state accommodation response exhibits temporal variations which can be characterized by two dominant regions of activity; a low frequency component (LFC < 0.6 Hz) and a high frequency component (1.0 < or = HFC < or = 2.1 Hz). There is no consensus as to the relative contribution made by each of the frequency components of the microfluctuations to the control of steady-state accommodation. We investigate the effect of variations in artificial pupil diameter (0.5, 1, 2, 3, 4 and 5 mm pupils) on the microfluctuations of accommodation, while three young emmetropic subjects view, monocularly, a photopic high contrast Maltese cross target placed at a dioptric distance equal to their open-loop accommodation level. Average power spectra were calculated for five accommodation signals, each of 10 sec duration, collected for each viewing condition at a sampling rate of 102.4 Hz using a continuously recording infrared objective optometer. For artificial pupil diameters < or = 2 mm the power of the LFC was found to increase as a function of reducing pupil diameter, while for artificial pupil diameters > 2 mm the LFC was found to be relatively constant. No systematic change in the HFC with varying artificial pupil diameter was observed. Changes in the root-mean-square (r.m.s.) value of the fluctuations with varying pupil diameter were significant (one-way ANOVA, F = 8.507, P = 0.0001, d.f. = 89) and showed a similar form to the changes in the LFC.(ABSTRACT TRUNCATED AT 250 WORDS)


Deficient response modulation and emotion processing in low-anxious Caucasian psychopathic offenders: results from a lexical decision task.
The clinical and research literatures on psychopathy have identified an emotion paradox: Psychopaths display normal appraisal but impaired use of emotion cues. Using R. D. Hare's (1991) Psychopathy Checklist-Revised and the G. S. Welsh Anxiety Scale (1956), the authors identified low-anxious psychopaths and controls and examined predictions concerning their performance on a lexical-decision task. Results supported all the predictions: (a) low-anxious psychopaths appraised emotion cues as well as controls; (b) their lexical decisions were relatively unaffected by emotion cues; (c) their lexical decisions were relatively unaffected by affectively neutral word-frequency cues; and (d) their performance deficits were specific to conditions involving right-handed responses. The authors propose that deficient response modulation may underlie both the emotional and cognitive deficits associated with low-anxious psychopaths.


Comparison between immunofluorescence and PCR in detecting human papilloma virus in condyloma acuminata.
To compare the effectiveness of immunofluorescence and polymerase chain reaction (PCR) in detecting human papilloma virus (HPV) in condyloma acuminata (CA). HPVs in CA tissues from 60 patients were detected by immunofluorescence and PCR, respectively. Different subtypes of HPVs were also identified with restriction fragment length polymorphism (RFLP). The positive detective rates of immunofluorescence and PCR were 56.67% (34/60) and 96.67% (58/ 60), respectively (P < 0.01). RFLP results showed HPV6 and HPV11 were the main subtypes in the detected virus, which accounted for 98.28%. The sensibility of PCR is superior to that of immunofluorescence.


Biomimetic self-assembly of a functional asymmetrical electronic device.
This paper introduces a biomimetic strategy for the fabrication of asymmetrical, three-dimensional electronic devices modeled on the folding of a chain of polypeptide structural motifs into a globular protein. Millimeter-size polyhedra-patterned with logic devices, wires, and solder dots-were connected in a linear string by using flexible wire. On self-assembly, the string folded spontaneously into two domains: one functioned as a ring oscillator, and the other one as a shift register. This example demonstrates that biomimetic principles of design and self-organization can be applied to generate multifunctional electronic systems of complex, three-dimensional architecture.


Efficacy of oral and parenteral ketoprofen in lactating cows with endotoxin-induced acute mastitis.
One hind quarter of 27 healthy lactating cows was infused with 100 microg Escherichia coli endotoxin. Two hours later, nine of the cows were given physiological saline by intramuscular injection, nine were given 4 mg/kg ketoprofen orally, and nine were given 3 mg/kg ketoprofen by intramuscular injection. Ketoprofen administered either orally or parenterally significantly reduced the effect of the endotoxin on rectal temperature, ruminal contractions and respiratory rate. The size of the udder, the signs of pain and the concentrations of thromboxane B2, especially in plasma, were also reduced, and the appearance of their milk was almost normal. The response of cows to the oral treatment was as rapid as it was to intramuscular treatment.


Drosophila Myc is required for normal DREF gene expression.
The Drosophila DNA replication-related element-binding factor (dDREF) is required for the expression of many proliferation-related genes carrying the DRE sequence, 5'-TATCGATA. Finding a canonical E-box, 5'-CACGTG, in the dDREF gene promoter prompted us to explore the possibility that the dDREF gene is a target of Drosophila Myc (dMyc). Luciferase transient expression assays combined with RNA interference in Drosophila S2 cells revealed that knockdown of dmyc reduced dDREF gene promoter activity by 35% to 82%, an effect at least partly mediated by the E-box in the promoter. dm(4)/Y hemizygous mutant larvae demonstrated no maternal dMyc and severe impairment of dDREF mRNA transcription. dMyc loss of function in dm(2)/dm(2) homozygous mutant follicle cell clones also resulted in loss of anti-dDREF immunostaining in nuclei. In contrast, co-expression of dMyc-dMax up-regulated dDREF promoter activity in S2 cells. Furthermore, dMyc over-expressing clones exhibited a high level of dDREF gene expression in wing and eye discs. These results taken together indicate that dMyc is indeed required for dDREF gene expression.


Adequacy of human milk viscosity to respond to infants with dysphagia: experimental study.
Neonatal nutrition is an important subject in health in the short, medium and long term. In preterm newborns, nutrition assumes a predominant role for the child's overall development. Babies with uncoordinated swallowing or respiration may not have the necessary oral abilities to suck the mother's breast and will need to implement different feeding practices; one of them is changing the consistency of the milk offered. Determine viscosity variations of untreated human and pasteurized milk without and with thickening to adapt the diet to the needs of dysphagic infants hospitalized in the Neonatal Intensive Cara Unit (NICU). The authors altered the viscosity of natural infant powdered milk and, after thickening, determined and adopted a thickening standard for human milk. Untreated human and pasteurized milk was thickened in concentrations of 2%, 3%, 5% and 7% and the viscosity were determined every 20 minutes for a period of 60 minutes at a temperature of 37ºC. The infant lactose formula thickened at concentrations of 2% and 3% produced viscosities of 8.97cP and 27.73 cP, respectively. The increases were significantly different after 1 hour. Inversely, untreated human milk at 2%, 3%, 5% and 7% produced diminished viscosity over time; the changes were more accentuated in the first 20 minutes. In pasteurized human milk, the 2% concentration had no variation in viscosity, but with the 3%, 5% and 7% concentrations, there was a significant decrease in the first 20 minutes with stability observed in the subsequent times. In powdered milk, the viscosity increases over time; the viscosity in human milk diminishes. The results point out the importance not only of considering the concentration of the thickener but also the time being administered after its addition to effectively treat dysphagic infants.


Nonlinear model on pulsatile flow of blood through a porous bifurcated arterial stenosis in the presence of magnetic field and periodic body acceleration.
Background and Objective: The motivation of cardiovascular modeling is to understand the haemodynamic and mechanical factors in the diagnosis and treatment of cardiovascular diseases. Several investigations have been carried out by many authors to understand the flow properties of blood in modelling blood flows in the circulatory system. In the present article, the pulsatile flow of Herschel-Bulkley fluid through a bifurcated arterial stenosis in a porous medium with magnetic field and periodic body acceleration has been investigated in view of understanding the role of rheological behaviour of blood, stenotic height, bifurcation angle, magnetic field and porosity of wall in the initiation and proliferation of cardiovascular diseases. The governing equations involving shear stress are solved numerically using finite difference schemes and the shear stress values in parent and daughter arteries are obtained using MATLAB software. The constitutive equation of Herschel-Bulkley fluid is highly nonlinear and using the equation, velocity distribution has been obtained. From the obtained velocity distribution, the numerical solutions of wall shear stress and flow resistance are found. The plug core radius is, for the first time, computed for various stenotic heights and it is found that the magnetic field and porosity increase the plug core radius. The wall shear stress and flow resistance increase as stenotic height, yield stress, power law index, consistency and Hartmann number increase and decrease with increase in Darcy number and half of the bifurcation angle. It is significant to note that when the value of yield stress is increased from 0.1 to 0.2, the plug core radius is increased by 7.3%. In the presence of yield stress in blood, the applied magnetic field causes 33.87% increase in the plug core radius. The mathematical model clearly shows that the increase in wall shear stress affects the aggregation of human platelets and rearranging the alignment of endothelial cells near the arterial wall. This implies that the wall shear stress is to be brought down below its critical level by increasing the values of Darcy number and half of the bifurcation angle. Further, the nature of increased flow resistance reduces the amount of blood supply to the vital organs which ultimately leads to a sudden death. This information is useful for bio-medical engineering in developing bio-medical instruments for a great potential treatment modalities inturn, prevent the causes of stroke, heart attack and renal failure.


Role of glutathione s-transferase polymorphisms and chronic allograft dysfunction.
Polymorphisms within genes encoding glutathione S-transferases (GSTs) may affect responses against damage induced by oxidative stress and therefore play a role to prevent chronic allograft dysfunction (CAD). In the present study, we estimated the frequencies of GSTM1- and GSTT1-null genotypes among 227 renal transplant recipients seeking to establish an association with CAD. Patients persistently displaying serum creatinine (sCr) values < or = 1.5 mg/dL, measured creatinine clearances (CLcr) > or = 50 mL/min/1.73 m(2), and 24-hour proteinuria < or = 500 mg were classified as normal graft function (NF; n = 107). In contrast, the CAD group (n = 120) presented sCr > 1.5 mg/dL, CLcr < 50 mL/min/1.73 m(2), and proteinuria > 500 mg. The GSTM1 and GSTT1 polymorphisms were evaluated by the multiplex polymerase chain reaction. The frequencies of GSTT1-null genotypes in NF and CAD cohorts were 15% and 24.2%, respectively (P = .057), while GSTM1-null genotypes in the same groups of patients were 44% and 46.7% (P = .389). A combination of null genotypes for GSTT1 and GSTM1 was observed in 9.2% of patients with CAD and in 5.6% of those with NF (P = .449). This study did not show an association of either GSTT1- and GSTM1-null genotypes with CAD. It is likely that development and progression of CAD are determined by a combination of complex genetic traits resulting from the interplay of several genes rather than a single gene.


Correction to: Hard- and soft-tissue profiles of the midface region in patients with skeletal Class III malocclusion using cone-beam computed tomography multiplanar-reconstructed image analysis.
[This corrects the article on p. 143 in vol. 48, PMID: 29732300.].


[An unusual sequela of a frequently occurring neurologic disorder: delirium caused by brain infarct].
Six patients are described with delirium after cerebral infarction. Five had a right-sided parietal infarction with involvement of the inferior parietal lobule. One patient presented with a right-sided medial temporo-occipital infarction. The mild neurological signs were dominated by the delirium. The outcome was good in all patients. Delirium after cerebral infarction is probably caused by injury to one of the convergence sites for integration of sensory information with disturbance of the directed attention to relevant stimuli. These sites are localized in the right parietal cortex and the medial temporo-occipital regions. This cause of delirium is probably compatible with the supposition that the right hemisphere is mainly responsible for the distribution of directed attention within extrapersonal space. The importance of an accurate neurological examination in delirious patients is emphasized.


Subtype switching of T-type Ca 2+ channels from Cav3.2 to Cav3.1 during differentiation of embryonic stem cells to cardiac cell lineage.
The developmental changes of Ni(2+)-sensitivity to automaticity of Nkx2.5-positive cells derived from mouse embryonic stem cell have been identified, suggesting developmental regulation of expressing Ni(2+)-sensitive T-type Ca(2+) channel, although the mechanism of the change has not been fully studied. Transcripts of Cav3.2, Cav3.1 and Cav1.2 genes of beating Nkx2.5-positive cells, which encode the Ni(2+)-sensitive T-type Ca(2+) channel, Ni(2+)-insensitive T-type Ca(2+) channel, and L-type Ca(2+) channel, respectively, were investigated by real-time reverse-transcriptase-polymerase chain reaction, and the current density of each channel was measured by patch-clamp techniques at the early and late stages of differentiation. The expression of the Cav3.2 transcript predominated in the early stage whereas those of Cav3.1 and Cav1.2 transcripts were upregulated in the late stage, which was consistent with the change in each current density, suggesting the expression of channel proteins is largely determined at the transcriptional level. The results indicate that the mechanism of change of Ni(2+)-sensitivity is partly, if not completely, the subtype switch of T-type Ca(2+) channel from Cav3.2 to Cav3.1 at the transcriptional level, and that the expression of the L-type Ca(2+) channel might have an attenuating effect on Ni(2+)-sensitivity to automaticity in the late stage of differentiation.


An Iron-Rich Diet Decreases the Mycobacterial Burden and Correlates With Hepcidin Upregulation, Lower Levels of Proinflammatory Mediators, and Increased T-Cell Recruitment in a Model of Mycobacterium bovis Bacille Calmette-Guerin Infection.
Recent evidence indicates a robust competition between the host and mycobacteria for iron acquisition during mycobacterial infection. Variable effects of iron supplementation on the susceptibility to mycobacterial infection have been reported. In this study, we revisited the effects of an experimental iron-enriched diet on Mycobacterium bovis bacille Calmette-Guerin (BCG) infection. Mice fed a standard diet or a diet moderately enriched with iron were infected with M. bovis BCG expressing green fluorescent protein. Colony-forming unit numbers, host myeloid cell counts, cell recruitment, cytokine production, and iron gene expression were determined at different stages of infection. Bone marrow-derived macrophages incubated with or without iron were also used to measure bacterial uptake, levels of inflammation markers, and iron gene expression. In vivo analysis of BCG-infected mice revealed that moderate iron supplementation reduced inflammation, as measured by decreased proinflammatory cytokine levels and neutrophil recruitment and enhanced T-cell recruitment in granulomas, and decreased the bacterial load. Enhanced bacterial clearance in the liver correlated with upregulation of the gene encoding hepcidin, which is known to have antimicrobial proprieties, and with sequestration of iron in tissues. In cultured macrophages, iron supplementation induced reactive oxygen species and reduced uptake and intracellular growth of BCG. Moderate iron diet supplementation diminished inflammation and growth of M. bovis BCG via enhanced reactive oxygen species production, immune cell activation, and local hepcidin expression.


Case Report. Diagnostic Challenges: Liver Metastases from Mammary Gland Origin or Cholangiocarcinoma?
Liver metastases are secondary malignant tumor formations due to the dissemination of primary malignant tumors, which are often the first clinical manifestation of mammary cancer. We present the case of a 52-year-old female patient from an urban area who came to the walk-in service at the "Sf. Ap. Andrei" Emergency County Hospital, Galati, for laboratory investigations. These revealed a significant increase in CA 15-3 tumor markers and a slight increase in CA 125 and CA 19-9 markers; however, clinical examination did not reveal tumors in the breast and there were no axillary adenopathies. CT exam revealed a large tumor formation in the hepatic right lobe and, close to it, a smaller one. The mammograph showed millimetric lesions at the level of the left mammary gland and bilateral axillary adenopathies. Subsequently, the patient underwent two liver biopsies in two different hospitals, which produced different histological and immunohistochemical results. PET-CT drew attention to a lung tumor and disclosed a different origin of metastases. In the end, correlating all investigations, the final diagnosis was cholangiocarcinoma with liver metastases and lung tumor with lung and bone metastases.


Repeatability of Dixon magnetic resonance imaging and magnetic resonance spectroscopy for quantitative muscle fat assessments in the thigh.
Changes in muscle fat composition as for example observed in sarcopenia or muscular dystrophy affect physical performance and muscular function, like strength and power. The purpose of the present study is to measure the repeatability of Dixon magnetic resonance imaging (MRI) for assessing muscle volume and fat in the thigh. Furthermore, repeatability of magnetic resonance spectroscopy (MRS) for assessing muscle fat is determined. A prototype 6-point Dixon MRI method was used to measure muscle volume and muscle proton density fat fraction (PDFF) in the left thigh. PDFF was measured in musculus semitendinosus of the left thigh with a T2-corrected multi-echo MRS method. For the determination of short-term repeatability (consecutive examinations), the root mean square coefficients of variation of Dixon MRI and MRS data of 23 young and healthy (29 ± 5 years) and 24 elderly men with sarcopenia (78 ± 5 years) were calculated. For the estimation of the long-term repeatability (13 weeks between examinations), the root mean square coefficients of variation of MRI data of seven young and healthy (31 ± 7 years) and 23 elderly sarcopenic men (76 ± 5 years) were calculated. Long-term repeatability of MRS was not determined. Short-term errors of Dixon MRI volume measurement were between 1.2% and 1.5%, between 2.1% and 1.6% for Dixon MRI PDFF measurement, and between 9.0% and 15.3% for MRS. Because of the high short-term repeatability errors of MRS, long-term errors were not determined. Long-term errors of MRI volume measurement were between 1.9% and 4.0% and of Dixon MRI PDFF measurement between 2.1% and 4.2%. The high degree of repeatability of volume and PDFF Dixon MRI supports its use to predict future mobility impairment and measures the success of therapeutic interventions, for example, in sarcopenia in aging populations and muscular dystrophy. Because of possible inhomogeneity of fat infiltration in muscle tissue, the application of MRS for PDFF measurements in muscle is more problematic because this may result in high repeatability errors. In addition, the tissue composition within the MRS voxel may not be representative for the whole muscle.


Angioleiomyoma of the hand with nerve compression.
This study was performed to analyze the clinical, radiographic, and pathological features of hand angioleiomyoma causing nerve compression and assess the outcomes of surgical excision. This case series included three men and one woman (mean age, 53.3 years; range, 49-56 years). The patients' chief complaint was numbness of the fingers. The patients' medical histories were reviewed, and the diagnosis of angioleiomyoma with nerve compression was confirmed by means of imaging examination and pathological analysis. Three tumors occurred in the palm and one in the finger, and the average maximum tumor diameter was 1.8 cm (range, 0.8-2.6 cm). Preoperative magnetic resonance imaging demonstrated well-defined masses with isointense signals on T1 sequences, hyperintense signals on T2 sequences, and strong heterogeneous enhancement after injection of contrast material. All tumors were located near nerves, leading to nerve compression. The diagnosis of angioleiomyoma was confirmed by postoperative pathology. Finger sensation recovered and no recurrence was found during an average follow-up of 37 months (range, 25-59 months). Angioleiomyoma should be considered among the differential diagnoses of hand tumors and timely resection should be performed, particularly if the mass is causing numbness and/or pain with positive Tinel's sign and/or tenderness.


In vitro binding studies suggest a membrane-associated complex between erythroid p55, protein 4.1, and glycophorin C.
p55 is a palmitoylated peripheral membrane phosphoprotein of human erythrocytes. Primary structure of p55 includes a single copy of the SH3 motif, a COOH-terminal guanylate kinase domain, and an NH2-terminal domain of unknown function. Although the function of p55 is not known, interest in this component has been heightened by its similarity to the Drosophila tumor suppressor discs-large (dlg). In this report we provide evidence for the direct association of p55 with the NH2-terminal 30-kDa domain of protein 4.1, a key component of the erythroid membrane skeleton. In addition, p55 also binds to the cytoplasmic domain of glycophorin C, a transmembrane protein of red blood cells. We also provide evidence demonstrating the direct association of the 30-kDa domain of protein 4.1 with the cytoplasmic domain of glycophorin C. Taken together, these results suggest the existence of a novel ternary complex at the erythroid plasma membrane involving protein 4.1, p55, and glycophorin C. Since isoforms of protein 4.1, p55, and glycophorin C are present in many non-erythroid cells, the binding interactions may be prototypical of similar associations that modulate cytoskeletal-membrane linkage of broad significance.


The genetic authentication of Panax ginseng and Panax quinquefolius based on using single nucleotide polymorphism (SNP) conducted in a nucleic acid test chip.
Panax ginseng and Panax quinquefolius, which are commonly called Chinese ginseng and American ginseng respectively, have different medicinal properties and market values; however, these samples can be difficult to differentiate from one another based on physical appearances of the samples especially when they are in powdery or granular forms. A molecular technique is thus needed to overcome this difficulty; this technique is based on the nucleic acid test (NAT) conducted on the microfluidic chip surface. Three single nucleotide polymorphism (SNP) sites (i.e. N1, N2, N3) on the Panax genome that differ between P. ginseng (G) and P. quinquefolius (Q) have been selected to design probes for the NAT. Primers were designed to amplify the antisense strands by asymmetric PCR. We have developed three different NAT methodologies involving surface immobilization and subsequent (stop flow or dynamic) hybridization of probes (i.e. N1G, N1Q, N2G, N2Q, N3Q) to the antisense strands. These NAT methods consist of two steps, namely immobilization and hybridization, and each method is distinguished by what is immobilized on the microfluidic chip surface in the first step (i.e. probe, target or capture strand). These three NATs developed are called probe-target method 1, target-probe method 2 and three-strand complex method 3. Out of the three methods, it was found that the capture strand-target-probe method 3 provided the best differentiation of the ginseng species, in which a 3' NH2 capture strand is first immobilized and the antisense PCR strand is then bound, while N2G and N3Q probes are used for detection of P. ginseng (G) and P. quinquefolius (Q) respectively.


Lysozyme activity in animal extracts after sodium dodecyl sulfate-polyacrylamide gel electrophoresis.
1. Lysozyme activity was detected after electrophoresis in sodium dodecyl sulfate-polyacrylamide gels containing 0.2% (W/V) autoclaved Micrococcus lysodeikticus cells as substrate. 2. Lysozyme activity appeared as clear lysis zones after incubation of opaque gels at 37 degrees C in buffered Triton X-100. 3. As low as 0.1 pg of purified hen egg white lysozyme could be detected after 16 hr incubation at pH 6.5. 4. Bands with lytic activity from kidney and pancreas acetone powders, bird's egg whites and vitelline membranes, animal sera and human saliva corresponded to c-type (Mr 14,500), g-type (Mr 20,500) or both lysozymes as far as molecular weight is concerned. 5. Some extracts, like porcine kidney, exhibited more than two bands. 6. Bands with lytic activity migrating at the level of g-type lysozymes were detected in some kidney and pancreas extracts.


Prevalence of markers of hepatotropic viruses among drug addicts in Warsaw, Poland.
We studied 100 unselected parenteral drug abusers for infection with hepatitis C, B, A and D virus (HCV, HBV, HAV and HDV). Seventy-six percent had serological evidence of HCV infection. 12% were positive for HBsAg and at least one marker of HBV infection was present in 69%. These results were significantly higher than in a matched control population. Compared to controls, the prevalence of anti-HAV (65%) was not significantly increased in drug addicts. Of the anti-HCV-positive drug addicts, 80.3% had at least one marker of HBV infection compared to 33.3% of anti-HCV-negative cases (p less than 0.001). No such correlation was found between the prevalence of HCV or HBV infection markers and the presence of anti-HAV. Antibodies against HDV were detected in 16 (16%) of the samples from drug addicts. No significant association was found between antibodies to HCV and gender, age and duration of drug abuse. The risk of HBV infection increased significantly with years of drug abuse but was not associated with age and sex. The presence of anti-HAV was related to age only. Sixteen (16%) of the subjects were definitely positive for anti-HIV-1, but at the time of the study they were asymptomatic. No significant association was found between the presence of anti-HIV and the prevalence of serological markers of HBV, HCV, HAV and HDV infection.