Identification of Differentially Expressed Proteins in the Serum of Colorectal Cancer Patients Using 2D-DIGE Proteomics Analysis.
Early detection of colorectal cancer (CRC) is vital for the improvement of disease prognosis. However to date there are no blood-based biomarkers sensitive and specific enough for early diagnosis. We analysed the differences in serum protein expression of early stage CRC (Dukes' A and B) and late stage CRC (Dukes' C and D) against normal controls using 2D Fluorescence Difference Gel Electrophoresis (2D-DIGE). Analysis of the 2D maps showed that 23 proteins were differentially expressed between groups (p≤0.05) and these proteins were identified with LC-MS/MS. Eight proteins were up-regulated and 2 down-regulated in patients with early CRC, whereas 14 proteins were up-regulated and 4 downregulated in those with late CRC compared to normal controls (p≤0.05). Five proteins, namely apolipoprotein A1 (APOA1), apolipoprotein E (APOE), complement factor H (CFH), galectin-7 (GAL7) and synaptojanin-2 (SYNJ2) were validated using ELISA and only APOA1 and GAL-7 showed consistent findings. Further validation using immunohistochemistry showed negative immunoreactivity for GAL-7 in CRC tissues, suggesting that GAL-7 detected in the serum did not originate from the CRC tumour. APOA1 showed positive immunoreactivity but its expression did not correlate with Dukes' staging (p=0.314), tumour grading (p=0.880) and lymph node involvement (p=0.108). Differences in APOA1 isoforms and/or conformation between serum and tissue samples as well as tumour heterogeneity may explain for the discrepancies between DIGE and ELISAwhen compared to immunohistochemistry. Structural and functional studies of APOA1 in future would best describe the role of APOA1 in CRC.


In vitro evaluation of amino acid prodrugs of novel antitumour 2-(4-amino-3-methylphenyl)benzothiazoles.
Novel 2-(4-aminophenyl)benzothiazoles possess highly selective, potent antitumour properties in vitro and in vivo. They induce and are biotransformed by cytochrome P450 (CYP) 1A1 to putative active as well as inactive metabolites. Metabolic inactivation of the molecule has been thwarted by isosteric replacement of hydrogen with fluorine atoms at positions around the benzothiazole nucleus. The lipophilicity of these compounds presents limitations for drug formulation and bioavailability. To overcome this problem, water soluble prodrugs have been synthesised by conjugation of alanyl- and lysyl-amide hydrochloride salts to the exocyclic primary amine function of 2-(4-aminophenyl)benzothiazoles. The prodrugs retain selectivity with significant in vitro growth inhibitory potency against the same sensitive cell lines as their parent amine, but are inactive against cell lines inherently resistant to 2-(4-aminophenyl)benzothiazoles. Alanyl and lysyl prodrugs rapidly and quantitatively revert to their parent amine in sensitive and insensitive cell lines in vitro. Liberated parent compounds are sequestered and metabolised by sensitive cells only; similarly, CYP1A1 activity and protein expression are selectively induced in sensitive carcinoma cells. Amino acid prodrugs meet the criteria of aqueous solubility, chemical stability and quantitative reversion to parent molecule, and thus are suitable for in vivo preclinical evaluation.


Enhanced-contrast optical readout in ultrafast broadband Raman quantum memories.
The signal-to-noise contrast of the optical readout in broadband Raman quantum memories is analyzed as a function of the pulse widths and phase properties of tailored optical field waveforms used to write in and read out broadband photon wave packets. Based on this analysis, we quantify the tradeoff between the readout contrast and the speed of such memories. Off-resonance coherent four-wave mixing is shown to provide a source of noise photons, lowering the readout contrast in broadband Raman quantum memories. This noise cannot be suppressed by phase matching, but can be radically reduced with a suitable polarization arrangement and proper field-waveform tailoring.


Do the benefits of rigid internal fixation of mandible fractures justify the added costs? Results from a randomized controlled trial.
Owing to its putative advantages over conventional maxillomandibular fixation (MMF), open-reduction and rigid internal fixation (ORIF) is used frequently to treat mandible fractures, particularly in noncompliant patients. The resource-intensive nature of ORIF, the large variation in its use, and the lack of systematic studies substantiating ORIF attributed benefits compel a randomized controlled investigation comparing ORIF to MMF treatment. The objective of this study was to determine whether ORIF provides better clinical and functional outcomes than MMF in noncomplying type of patients with a similar range of mandible fracture severity. From a total of 336 patients who sought treatment for mandible fractures, 142 patients with moderately severe mandible fractures were assigned randomly to receive MMF or ORIF and followed prospectively for 12 months. A variety of clinician and patient-reported measures were used to assess outcomes at the 1, 6, and 12 months follow-up visits. These measures included clinician-reported number of surgical complications, patient-reported number of complaints, as well as cumulative costs of treatment. Pain intensity was measured on a 10-point scale and the 12-item General Oral Health Assessment Index was used to assess the patients' oral health-related quality of life. Because the protocol allowed clinical judgment to overrule the randomly assigned treatment, outcomes were compared on an "intent-to-treat" basis as well as in terms of actual treatment received. The sociodemographic and clinical characteristics of the injury did not differ among the 2 groups. On an intent-to-treat basis, the difference in complication rates was not significant but favored MMF; 8.1% of patients developed complications with MMF versus 12.5% with ORIF. Differences in the rate of patient complaints were not significant on an intent-to-treat basis, but a significant between-group difference (P = .012) favoring MMF was noted on an as-treated basis at the 1 month recall, with 40% of ORIF patients reporting greater than 1 complaint versus 18.8% of MMF patients. No significant differences were detected between the 2 treatment groups at any time point with respect to oral health-related quality of life reflected by the General Oral Health Assessment Index scores. In-patient days and total costs did not differ significantly on an intent-to-treat basis, but on an as-treated basis, patients treated with MMF had fewer in-patient days on average (1.64 vs 5.50 for ORIF) and lower average costs of treatment ($7,206 vs $26,089 for ORIF). In the intent-to-treat analyses, patients receiving MMF treatment had significantly lower (P = .05) pain scores at the 12-month recall (mean = 0.58, SE = 0.30) compared with patients assigned to ORIF (mean = 1.78, SE = 0.52). Our study did not show a clear overall benefit of the resource-intensive ORIF over conventional MMF treatment in the management of moderately severe mandible fractures in at-risk patients; our data instead suggest some cost as well as oral health quality-of-life advantages for the use of MMF in this patient population.


SERS combined with the difference in bacterial extracellular electron transfer ability to distinguish Shewanella.
Shewanella plays an important role in geochemical cycle, biological corrosion, bioremediation and bioenergy. The development of methods for identifying Shewanella can provide technical support for its rapid screening, in-depth research into its extracellular respiratory mechanism and its application in ecological environment remediation. As a tool for microbial classification, identification and detection, Surface-enhanced Raman scattering (SERS) has high feasibility and application potential. In this work, bio-synthesized silver nanoparticles (AgNPs) were used as SERS substrates to effectively distinguish different types of Shewanella bacteria based on the difference in bacterial extracellular electron transfer (EET) ability. AgNPs were combined with the analyzed bacteria to prepare "Bacteria-AgNPs" SERS samples, which can strongly enhance the Raman signal of the target bacteria and reliably obtain spatial information of different molecular functional groups of each bacteria. Our developed approach can effectively distinguish between non-metal reducing and metal-reducing bacteria, and can further distinguish the three subspecies of Shewanella (Shewanella oneidensis MR-1, Shewanella decolorationis S12, and Shewanella putrefaciens SP200) at the genus and species level. The Raman signal enhancement is presumably caused by the excitation of local surface plasma (LSP) and the enhancement of surrounding electric field. Therefore, our developed method can achieve interspecific and intraspecies discrimination of bacteria. The proposed method can be extended to distinguish other metal-reducing bacteria, and the novel SERS active substrates can be developed for practical applications.


Effectiveness of speak-up training programs for clinical nurses: A scoping review.
Speaking up about patient safety concerns is critical when bedside nurses encounter unsafe situations. Training programs that encourage nurses' speaking up behavior have been introduced, but there is limited evidence regarding whether such training leads to behavior change or improves patient safety. The aim of this review was to identify the effectiveness of speak-up training programs for clinical nurses, focusing on program content and outcomes. A scoping review was conducted using the Joanna Briggs Institute methodology and reported according to the Cochrane and Preferred Reporting Items for Systematic Review and Meta-Analyses Extension for Scoping Reviews guidelines. This study used bibliographic databases of PubMed, Embase, PsycINFO, Scopus, ProQuest Dissertations and Theses Global for the English language, and NDSL, KCI, RISS, KISS, and DBpia for the Korean language. The literature search used a combination of keywords and subject headings related to speak-up training programs for nurses or any type of nurse training program with an assertiveness component. Training outcomes were evaluated according to the 4-level Kirkpatrick model. A total of 4808 references were retrieved, of which 21 articles were selected. These 21 studies were conducted in different parts of the world and published from 1981 to 2020. Speak-up training primarily increased some degree of nurses' levels of assertiveness and speak-up behavior, and also led to secondary outcomes such as job stress, work motivation, and communication conflicts. Most studies (n = 19) applied traditional training formats which consisted of multi-session lectures and practice, whereas three studies applied new methodologies such as high-fidelity simulations and online learning. According to the Kirkpatrick model, five studies assessed reactions to speak-up training (level 1), all studies evaluated learning as a result of training (level 2), two studies measured the effect of speak-up training on nurses' behavior (level 3), and one study evaluated nurses' results (level 4) while no studies evaluated patient-level outcomes. Speak-up training for nurses can improve their levels of assertiveness or speak-up behaviors. Despite inconsistent or mixed findings, speak-up training has the potential to improve nurses' psychological well-being, leading to positive organizational performance. New training methods are directed at specialized education for clinical situations. Future speak-up training should consist of training programs based on real clinical situations in which team members participate together to comprehensively evaluate the effect of training on behavioral changes of health professionals as well as patient safety.


[Sturge-Weber-Krabbe syndrome. A severe form in a monozygote female twin].
We report a severe case of Sturge-Weber syndrome in one of two monozygotic twins. This syndrome included a facial portwine stain over the trigeminal ophthalmic V1 area, and ipsilateral vascular anomalies of the eye and of the pia mater. CT scans and MRI were very informative. The cerebral regional blood flow, studied with SPECT, showed a paradoxically high rate.


Retrograde dissection of the adnexa in residual ovary syndrome.
Injuries to the ureter in the course of gynecologic procedures can occur frequently. The usual histologic signs and symptoms of peri-oophoritis, adhesion and distorted anatomy encountered with residual ovaries make their ablation hazardous to the surrounding structures and the ureter in particular. A method is described and illustrated to facilitate surgical extirpation and render the procedure safe.


Quantitative detection of hepatitis B virus DNA in two international reference plasma preparations. Eurohep Pathobiology Group.
Quantitative detection of hepatitis B virus (HBV) in serum or plasma is of significance for monitoring of therapy and establishment of the prognosis of the disease, as well as for infectivity assessment and quality control of the diagnosis. Unfortunately, various commercially available test kits for HBV DNA yielded conflicting quantitative results, with differences of up to a factor of 120. The Eurohep Pathobiology Group has established two reference samples of plasma from HBV carriers and determined as accurately as possible the number of HBV DNA molecules in these samples. Plasma donations from two single highly viremic carriers of HBV genotype A (HBV surface antigen subtype adw2) and genotype D (ayw2/3), respectively, were collected, and coded dilutions of these samples were analyzed by members of the Eurohep Pathobiology Group. Quantitative results from the seven laboratories reporting consistent results were initially divergent. Limiting dilution and nested PCR assays suffered from incomplete DNA extraction. Hybridization assays used inaccurately quantitated cloned DNA as a reference. Two hybridization assays could not be calibrated directly with cloned HBV DNA, because virion-derived DNA reacted much less efficiently. After identification and elimination of these problems, limiting-dilution assays from three laboratories and hybridization assays from two producers generated consistent and concordant results: 2.7 x 10(9) HBV DNA molecules/ml (range, 2.1 x 10(9) to 3.4 x 10(9) HBV DNA molecules/ml) in the plasma from the carrier of genotype A and 2.6 x 10(9) HBV DNA molecules/ml (range, 2.1 x 10(9) to 3.0 x 10(9) HBV DNA molecules/ml in the plasma from the carrier of genotype D. The two Eurohep reference plasma samples have already been used for the standardization of test kits and in quality control trials, and the plasma from the carrier of genotype A will probably be the basis of a World Health Organization reference sample.


Responses of antioxidant systems in the hepatocytes of common carp (Cyprinus carpio L.) to the toxicity of microcystin-LR.
The freshwater, bloom-forming cyanobacterium (blue-green alga) Microcystis aeruginosa produces a peptide hepatotoxin, which causes the damage of animal liver. Recently, toxic Microcystis blooms frequently occur in the eutrophic Dianchi Lake (300 km2 and located in the South-Western of China). Microcystin-LR from Microcystis in Dianchi was isolated and purified by high performance liquid chromatography (HPLC) and its toxicity to mouse and fish liver was studied (Li et al., 2001). In this study, six biochemical parameters (reactive oxygen species, glutathione, superoxide dismutase, catalase, glutathione peroxide and glutathione S-transferase) were determined in common carp hepatocytes when the cells were exposed to 10 microg microcystin-LR per litre. The results showed that reactive oxygen species (ROS) contents increased by more than one-time compared with the control after 6 h exposure to the toxin. In contrast, glutathione (GSH) levels in the hepatocytes exposed to microcystin-LR decreased by 47% compared with the control. The activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxide (GSH-Px) increased significantly after 6 h exposure to microcystin-LR, but glutathione S-transferase (GST) activity showed no difference from the control. These results suggested that the toxicity of microcystin-LR caused the increase of ROS contents and the depletion of GSH in hepatocytes exposed to the toxin and these changes led to oxidant shock in hepatocytes. Increases of SOD, CAT and GSH-Px activities revealed that these three kinds of antioxidant enzymes might play important roles in eliminating the excessive ROS. This paper also examined the possible toxicity mechanism of microcystin-LR on the fish hepatocytes and the results were similar to those with mouse hepatocytes.


Semaphorin3f as a cardiomyocyte derived regulator of heart chamber development.
During development a pool of precursors form a heart with atrial and ventricular chambers that exhibit distinct transcriptional and electrophysiological properties. Normal development of these chambers is essential for full term survival of the fetus, and deviations result in congenital heart defects. The large number of genes that may cause congenital heart defects when mutated, and the genetic variability and penetrance of the ensuing phenotypes, reveals a need to understand the molecular mechanisms that allow for the formation of chamber-specific cardiomyocyte differentiation. We used in situ hybridization, immunohistochemistry and functional analyses to identify the consequences of the loss of the secreted semaphorin, Sema3fb, in the development of the zebrafish heart by using two sema3fb CRISPR mutant alleles. We find that in the developing zebrafish heart sema3fb mRNA is expressed by all cardiomyocytes, whereas mRNA for a known receptor Plexina3 (Plxna3) is expressed preferentially by ventricular cardiomyocytes. In sema3fb CRISPR zebrafish mutants, heart chamber development is impaired; the atria and ventricles of mutants are smaller in size than their wild type siblings, apparently because of differences in cell size and not cell numbers. Analysis of chamber differentiation indicates defects in chamber specific gene expression at the border between the ventricular and atrial chambers, with spillage of ventricular chamber genes into the atrium, and vice versa, and a failure to restrict specialized cardiomyocyte markers to the atrioventricular canal (AVC). The hypoplastic heart chambers are associated with decreased cardiac output and heart edema. Based on our data we propose a model whereby cardiomyocytes secrete a Sema cue that, because of spatially restricted expression of the receptor, signals in a ventricular chamber-specific manner to establish a distinct border between atrial and ventricular chambers that is important to produce a fully functional heart. Video abstract.


The selective BACE1 inhibitor VIa reduces amyloid-β production in cell and mouse models of Alzheimer's disease.
β-site amyloid-β protein precursor cleaving enzyme 1 (BACE1) is the first protease and the rate limiting enzyme in the genesis of amyloid-β (Aβ). This protein remains an important potential disease-modifying target for the development of drugs to treat Alzheimer's disease (AD). We are pursuing potent BACE1 inhibitors in an effort to identify suitable AD drug candidates. Our results have shown that the novel compound VIa exhibits potent inhibitory effects with IC50 = 5.9 nM and displays 30.8-fold, 7500-fold and 17533-fold selectivity against the other aspartic proteases BACE2, cathepsin D and renin, respectively. In cellular assays, VIa moderately reduces Aβ production: Aβ(1-40) with an IC50 = 143 nM and 1 nM VIa reduced Aβ(1-42) by 40.17%. Concomitant with VIa inhibiting the β-cleavage of amyloid-β protein precursor (AβPP), VIa increases the production of sAβPPα with an approximate EC50 of 16.5 nM. In testing this compound's efficacy in vivo, the oral administration of VIa resulted in a significant decrease in Aβ(1-40) and Aβ(1-42) in the blood of a mouse model of AD by 17.5-72.44% and 14.5-80.32%, respectively. This indicates that the novel compound VIa is a small, potent, selective, and non-peptidic BACE1 inhibitor.


Transformation of electrospun Keratin/PVA nanofiber membranes into multilayered 3D Scaffolds: Physiochemical studies and corneal implant applications.
In this study, we engineered an electrospun keratin/polyvinyl alcohol (PVA) nanofiber membrane with a three-dimensional (3D) fiber network. Both keratin and PVA are known as biocompatible materials, and the 3D assembly of these two led to a transparent membrane with superior mechanical properties. The as-prepared three-dimensionally assembled keratin/PVA nanofiber (3D keratin/PVA NFs) membrane was characterized by state-of-the-art techniques and used as a corneal implant in rabbit eyes. The transparency, mechanical properties, and biocompatibility of the electrospun keratin/PVA NFs were highly enhanced after 3D modification which is mainly attributed to its unique three-dimensional morphology. The performance of 3D keratin/PVA NFs membrane was compared with horse amniotic membrane (AM), and the results obtained from the clinical and histological evaluations showed that it could be considered as an alternative material to the AM. Furthermore, this study provides an emerging approach for converting a two-dimensional electrospun nanofiber membrane to three-dimensional fiber networks that resemble the structure of the extracellular matrix (ECM).


When Genome Maintenance Goes Badly Awry.
Genetic abnormalities are present in all tumor types, although the frequency and type can vary. Chromosome abnormalities include highly aberrant structures, particularly chromothriptic chromosomes. The generation of massive sequencing data has illuminated the scope of the mutational burden in cancer genomes, identifying patterns of mutations (mutation signatures), which have the potential to shed light on the relatedness and etiologies of cancers and impact therapy response. Some mutation patterns are clearly attributable to disruptions in pathways that maintain genomic integrity. Here we review recent advances in our understanding of genetic changes occurring in cancers and the roles of genome maintenance pathways.


Gastrointestinal Lymphoma: Radiologic-Pathologic Correlation.
Extranodal lymphoma is a heterogeneous group of hematologic neoplasms that can affect every abdominal organ, with distinctive pathologic, radiologic, and clinical features. The radiologic findings are closely related to the underlying pathophysiology, and an understanding of these characteristic features should facilitate recognition of extranodal lymphoma and its various subtypes. Within the abdomen, lymphoma is found most commonly in the gastrointestinal tract, especially the stomach. This article presents the findings in gastrointestinal tract lymphoma.


Shepherd's crook deformity of polyostotic fibrous dysplasia treated with corrective osteotomy and dynamic hip screw.
Fibrous dysplasia, a condition in which the skeleton fails to develop normally, is characterized by fibroblastic stroma and immature bone. Bowing of the long bones occurs frequently in the polyostotic form, and stress fractures often result. Shepherd's crook deformity is a characteristic feature of fibrous dysplasia. The goal of its treatment is to obtain normal walking ability and relieve pain due to pathologic fracture secondary to the deformity; however, correction of the deformity is a surgical challenge. We present 2 cases of shepherd's crook deformity treated with corrective osteotomy and a dynamic hip screw. Both cases showed good bone healing and no recurrent deformity. The gross deformities were corrected, and both patients were pain-free after operation.


Successful treatment of suspected organizing pneumonia in a patient without typical imaging and pathological characteristic: A case report.
Organizing pneumonia (OP) is a clinicopathological entity characterized by granulation tissue plugs in the lumen of small airways, alveolar ducts, and alveoli. Diagnosis of OP needs the combination of clinical features, imaging and pathology. But it occurs often that there are no typical pathological features to support the diagnosis, which poses a challenge for clinicians' diagnosis and treatment. We diagnosed a case of OP without typical imaging and pathological characteristic and treated successfully. Finally we confirmed the pathological diagnosis. Not every OP case is supported by pathological evidence and typical imaging changes. It is important for us to judge and decide the diagnosis according to clinical experience.


Retracted: Innovation of Platform Economy Business Model Driven by BP Neural Network and Artificial Intelligence Technology.
[This retracts the article DOI: 10.1155/2022/3467773.].


Idiopathic chondrolysis of the hip: management by subtotal capsulectomy and aggressive rehabilitation.
Three cases of idiopathic chondrolysis were treated by a subtotal circumferential capsulectomy with follow-up for 3 years and 1 month. Concomitant muscle releases were performed as necessary to relieve joint contractures. Surgery was followed by an aggressive rehabilitation effort. All patients were symptom-free and displayed an extremely satisfactory range of motion. Radiographs revealed reconstitution of the joint space in all cases. We believe that this aggressive management is well justified when one considers the results of previous published reports.


"Innocent" arytenoid adduction asymmetry: An etiological survey.
To estimate the incidence of "innocent" arytenoid adduction asymmetry (AAA) among patients presenting at a laryngology clinic, identify its association with demographic characteristics, symptomatology and various clinical/pathological conditions and thereby determine its clinical significance. A prospective comparative observational clinical study was conducted. Group 1 included patients presenting at the Department of Laryngology, identified with a primary diagnosis and coexisting "innocent" AAA i.e., an overriding arytenoid with normal vocal fold mobility on laryngoscopy. Group 2 included an equal number of randomly selected patients fulfilling the same criteria, without AAA. Demographic and clinical details were recorded and analyzed. 110 cases were included in each group. The incidence of innocent AAA was 12.7%. Males were predominant in both Groups, with the gender difference significant in Group 1. Patients in Group 1 were significantly younger than in Group 2. Professional voice users, namely singers, were significantly greater in Group 1. Symptoms associated with Group 1 (i.e. AAA) were high pitch strain while singing (p = 0.01) and unilateral throat pain (p = 0.01), and the associated diagnoses were Singing Voice Dysphonia (p = 0.005), Vocal Process Granuloma (p = 0.04) and Ventricular Band Dysphonia (p = 0.047). As a definitive diagnosis was made in all patients, the presenting complaints were not attributed to AAA. Right sided preponderance of AAA was significant. Among the diagnoses with a laterality (e.g. vocal process granuloma), AAA was observed contralateral to the pathology in 70.7% and ipsilaterally in 29.3% (p = 0.0058). Innocent AAA is common among males in the 3rd-4th decades, in singers among professional voice users, and in those with the muscle tension dysphonia spectrum and vocal process granuloma, thereby suggesting that it is an acquired habit/response to greater vocal demand. The observation of AAA contralateral to laryngeal lesions, highlights its compensatory nature, attempting to optimize glottic closure.


CD44S-hyaluronan interactions protect cells resulting from EMT against anoikis.
The detachment of normal epithelial cells from matrix triggers an apoptotic response known as anoikis, during homeostatic turnover. Metastatic tumor cells evade anoikis, by mechanisms that are only partly characterized. In particular, the epithelial-mesenchymal transition (EMT) in a subset of invasive tumor cells confers anoikis-resistance. In some cases, EMT up-regulates the cancer stem cell marker CD44S and the enzyme hyaluronic acid synthase-2 (HAS2). CD44S is the major receptor for hyaluronan in the extracellular matrix. Herein, we demonstrate that CD44S, unlike the CD44E isoform expressed in normal epithelial cells, contributes to the protection against anoikis. This protection requires the interaction of CD44S with hyaluronan (HA). CD44S-HA interaction is proposed to play an important role in tumor metastasis through enhanced cell survival under detached conditions.


Presurgical assessment of flow variability in an azygos vein aneurysm using 4D-flow MRI.
Azygos vein aneurysm (AVA) is necessary to prevent pulmonary embolism due to the outflow of a thrombus or rupture of the aneurysm. However, there is no established modality to assess the properties of AVA. Time-resolved three-dimensional phase-contrast magnetic resonance imaging (4D-flow MRI) has been used to examine the hemodynamics in various fields. We report a case of AVA to evaluate the flow variability and adhesions of surrounding tissues using 4D-flow MRI. The findings of the study suggested aneurysm turbulence and the absence of thrombi. The cine image, which showed a sliding wall synchronized to the heartbeat, indicated no adhesion to the superior vena cava. Based on these results, the thoracoscopic approach was deemed possible preoperatively. Thoracoscopic AVA resection was performed, and the postoperative course was uneventful. This study documented the utility of 4D-flow MRI for a detailed evaluation of AVA.


Biomechanical characteristics of nonbridging external fixators for distal radius fractures.
Nonbridging external fixation is becoming popular for distal radius fractures, although its biomechanical characteristics have not been documented. This study evaluated the biomechanical characteristics of nonbridging external fixators for distal radius fractures. We tested 3 currently available nonbridging fixators (F-Wrist fixator, Hoffman II Compact, and Pennig Dynamic Wrist Fixator) and determined their relative stiffness under axial compression, torsion, and bending moments (dorsal, volar, radial, and ulnar aspects) using a uniform unstable distal radius fracture model. The contact pressure and its total load on the fracture plane were also measured to evaluate the mechanical stimuli at the stable fracture site using a pressure-sensitive conductive rubber sensor. Differences were observed in the stiffness: the Pennig fixator was the stiffest, whereas the F-Wrist fixator was the least rigid. The total load transmitted from the wrist joint to the fracture plane depended on the fixator stiffness in axial compression. By determining the biomechanical characteristics of nonbridging external fixators, these data may help the clinician when deciding on a particular device for nonbridging external fixation.


Nurses and pharmacists partner for patient safety.
Professions face serious challenge of work force shortages. Leaders of five organizations come together in first step of ambitious journey. Revolutionary changes, not quick fixes, seen as solution.


Urethral extensibility applied to reconstructive surgery.
The human male urethra has great capacity to extend under traction. This extensibility is the principle of some surgical techniques used to overcome urethral defects and for penile lengthening. However, to our knowledge safe limits of urethral extensibility in reconstructive surgery have not been yet established by a morphological study. To this end we measured fresh human cadaveric urethras with and without traction. We analyzed the macroscopically normal, fresh cadaveric urethra from 25 men 6 months to 73 years old at death (mean age 30.6). Penile length and length of the total, penile, bulbar and membranous urethra were measured. Length under maximal constant traction and the maximal stretched length without penile curvature at artificial erection were determined. Extensibility is expressed as the percent of the variation in initial length at rest and maximal constant traction length. Maximal stretched length without penile curvature at artificial erection is expressed as a percent of maximal constant traction length. Total urethral extensibility was higher than penile extensibility (p <0.001). Urethral extensibility decreased with aging (r = -0.806, p <0.001). Mean extensibility of the whole male urethra was 66.2% +/- 7.2% and differences among urethral segments were not significant (p = 0.283). Mean maximal stretched length without penile curvature at artificial erection was 75.2% +/- 3.8% and it did not change with age. Knowledge of the safe anatomical limit of urethral extensibility applied to reconstructive surgery may avoid complications and the necessity for more complex techniques. This limit should be approximately 75% of the maximal constant traction length or a gap-to-normal urethra ratio of 1:4. However, age related variations should be considered.


Assessing hepatomegaly: automated volumetric analysis of the liver.
The aims of this study were to define volumetric nomograms for identifying hepatomegaly and to retrospectively evaluate the performance of radiologists in assessing hepatomegaly. Livers were automatically segmented from 148 abdominal contrast-enhanced computed tomographic scans: 77 normal livers and 71 cases of hepatomegaly (diagnosed by visual inspection and/or linear liver height by radiologists). Quantified liver volumes were compared to manual measurements using volume overlap and error. Liver volumes were normalized to body surface area, from which hepatomegaly nomograms were defined (H scores) by analyzing the distribution of liver sizes in the healthy population. H scores were validated against consensus reports. The performance of radiologists in diagnosing hepatomegaly was retrospectively evaluated. The automated segmentation of livers was robust, with volume overlap and error of 96.2% and 2.2%, respectively. There were no significant differences (P > .10) between manual and automated segmentation for either the normal or the hepatomegaly subgroup. The average volumes of normal and enlarged livers were 1.51 ± 0.25 and 2.32 ± 0.75 L, respectively. One-way analysis of variance found that body surface area (P = .004) and gender (P = .02), but not age, significantly affected normal liver volume. No significant effects were observed for two-way and three-way interactions among the three variables (P > .18). H-score cutoffs of 0.92 and 1.08 L/m2 were used to define mild and massive hepatomegaly (95% confidence interval, ± 0.02 L/m2). Using the H score as the reference standard, the sensitivity of radiologists in detecting all, mild, and massive hepatomegaly was 84.4%, 56.7%, and 100.0% at 90.1% specificity, respectively. Radiologists disagreed on 20.9% of the diagnosed cases (n = 31). The area under the receiver-operating characteristic curve of the H-score criterion for hepatomegaly detection was 0.98. Nomograms for the identification and grading of hepatomegaly from automatic volumetric liver assessment normalized to body surface area (H scores) are introduced. H scores match well with clinical interpretations for hepatomegaly and may improve hepatomegaly detection compared with height measurements or visual inspection, commonly used in current clinical practice.


Probing protein-protein interaction in biomembranes using Fourier transform infrared spectroscopy.
The position, intensity and width of bands in infrared spectra that arise from vibrational modes within a protein can be used to probe protein secondary structure, amino acid side chain structure as well as protein dynamics and stability. FTIR spectroscopic studies on protein-protein interaction have been severely limited due to extensive overlap of peaks, from the interacting proteins. This problem is being addressed by combining data processing and acquisition techniques (difference spectroscopy and two-dimensional spectroscopy) with judicious modifications in the protein primary structure through molecular biological and chemical methods. These include the ability to modify amino acids (site-directed mutagenesis; chemical synthesis) and produce isotopically labelled proteins and peptides. Whilst great progress is being made towards overcoming the congestion of overlapping peaks, the slow progress in the assignment of bands continues to be a major hindrance in the use of infrared spectroscopy for obtaining highly accurate and precise information on protein structure. This review discusses some of these problems and presents examples of infrared studies on protein-protein interaction in biomembrane systems. This article is part of a Special Issue entitled: FTIR in membrane proteins and peptide studies.


Augmentation of protective immune responses against Sendai virus infection by fungal polysaccharide schizophyllan.
When treated with fungal polysaccharide schizophyllan, mice survived otherwise lethal Sendai virus infection. Both intraperitoneal and oral administrations were effective when sonicated schizophyllan with a relative molecular mass (M(r)) of 4.6 x 10(5) was used. Antiviral antibody in the serum could be detected at an earlier time after virus infection and virus spread in the lung was more efficiently inhibited in schizophyllan-treated mice than in untreated controls. Schizophyllan also augmented protective immune responses induced by low doses of a live Sendai virus vaccine that were insufficient to confer complete protection against challenge infection with a virulent strain. On the other hand, schizophyllan did not influence interferon production in mice whether or not infected with Sendai virus. The present results suggest that schizophyllan confers better protection against virus infection through augmentation of antiviral immune responses and can be used as an immune enhancer.


Toxicity and metal content of organic solvent extracts from airborne particulate matter in Puerto Rico.
The importance of airborne particulate matter (PM) in causing increases in morbidity and mortality in humans has been confirmed by numerous epidemiological and laboratory studies. It has been proposed that PM might deliver transition metals to the airways were they react and generate reactive oxygen species (ROS), thus promoting the expression of inflammatory mediators, and cytotoxicity. In Puerto Rico (PR), the northern Guaynabo area is a US EPA non-attainment zone for PM10 (PM with a mass median aerodynamic diameter 10 microm), and a previous study found that organic PM10 extracts from this area were cytotoxic. The purpose of this research project is to compare the toxicity between organic PM extracts from Guaynabo (a coastal urban site) and Fajardo (a coastal rural town) based on their polarity, collection season, and geographical location. We will also evaluate if the metal content of such extracts is associated with their biological activity. PM10 filters from both locations were subjected to a sequential Soxhlet extraction using hexane and acetone. Normal and transformed bronchial epithelial cells were then exposed to the extracts. Using the neutral red assay to measure cell viability we found that coastal urban PM from PR generally exhibits higher cytotoxicity than coastal rural PM. However, this effect is dependent on the polarity of the extracts and the collection season (in winter hexane PM10 is more toxic, whereas during the summer acetone PM10 is more toxic). We also found that non-polar organic constituents in PM from PR are generally more toxic than the polar organic constituents. The main conclusion from this work is that the metal contents of the organic PM extracts from PR could play a minor role in the cytotoxicity observed. This is supported by the findings of elements such as As, V, Ni, and Cu in the most cytotoxic extracts. However, organic compounds probably play the major role. The presence of bioactive fractions of PM underscores the importance of conducting more detailed studies.


Comparison of the improving embryo development effects of Sasa quelpaertensis Nakai extract, p-coumaric acid, and myricetin on porcine oocytes according to their antioxidant capacities.
This study investigated the antioxidant activities of Sasa quelpaertensis Nakai extract (SQE), p-coumaric acid (PCA) and myricetin (MY), and their effects on the in vitro maturation and developmental ability of porcine oocytes. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) showed that 1 mg of SQE contained 3.92 μg of PCA and 0.19 μg of MY. The concentrations required to inhibit 50% of DPPH radicals were 2732.8 ppm, 38.8 mg/mL, and 0.110 mg/mL for SQE, PCA, and MY, respectively. The reducing power increased as the concentration increased, and the reducing power of MY was higher than that of PCA. The polar body extrusion rate was highest upon treatment with 1250 ppm SQE and 10 μM MY. The reactive oxygen species and glutathione levels were significantly decreased and increased, respectively. In a normal or peroxidative environment, the embryo development rate upon parthenogenetic activation was increased, and the total cell number, apoptosis rate, and development-related gene expression were altered to enhance embryonic development. The embryo development rate and total cell number upon somatic cell nuclear transfer did not differ between the groups. These results show that the antioxidant effects of SQE and MY enhance the in vitro maturation and subsequent embryonic development.


Ex vivo elimination of lymphoblastic leukemia cells from human marrow by mafosfamid.
Studies were performed to evaluate the anti-tumor activity of mafosfamid, a new synthetic derivative of cyclophosphamide. We tested its ability to eliminate lymphoblastic leukemia cells from autologous bone marrow grafts following a 30 min preincubation in a highly sensitive clonogenic assay. Treatment with 50-100 micrograms mafosfamid/ml eliminated more than 4 logs of contaminating clonogenic tumor cells from a 200-fold excess of normal bone marrow. Flow cytometric studies showed differences in cell cycle kinetics between mafosfamid-resistant and mafosfamid-susceptible tumor cell clones. Compared to drug susceptible clonogenic tumor cells, clones that resisted treatment with 100 micrograms mafosfamid/ml exhibited a smaller percentage of cells in S-phase, indicating that mafosfamid is mostly cytotoxic to rapidly cycling tumor cells. The combination of mafosfamid and a target cell selective immunotoxin containing pokeweed anti-viral protein was superior to mafosfamid alone or immunotoxin alone for purging mafosfamid-resistant leukemic cells from human marrow.


Entropy measures for discrimination of 'awake' Vs 'anaesthetized' state in recovery from general anesthesia.
Approximate Entropy (ApEn) and Permutation Entropy (PE) have been recently introduced for assessment of anesthetic depth. Both measures have previously been shown to track changes in the electrical brain activity related to the administration of anesthetic agents. In this paper ApEn and PE are compared for the automatic classification of 'awake' and 'anesthetized' state using a Support Vector Machine to assess their robustness for potential use in a device for monitoring awareness during general anesthesia. It was found that both measures provide linearly separable features and we are able to discriminate between the two states with accuracy greater than 96% using either of the two entropy measures.


The role of systemic inflammatory cells in meningiomas.
The aim of this review is to describe the inflammatory systemic cell infiltrate and its role in pathophysiology and prognostic implications of meningiomas. Articles from PubMed describing inflammation and immune cells in meningioma were systematically selected and reviewed. Infiltrating inflammatory cells are common in meningiomas and correlate with tumor behavior and peritumoral edema. The immune cell infiltrate mainly comprised macrophages, CD4 + T cells of the Th1 and Th2 subtype, CD8 + cytotoxic T cells, mast cells, and to a lesser degree B cells. The polarization of macrophages to M1 or M2 states, as well as the differentiation of T-helper cells to Th1 or Th2 subsets, is of prognostic value, but whether or not the presence of macrophages is associated with the degree of malignancy of the tumor is controversial. The best documented immunosuppressive and tumor-promoting mechanism is the expression of programmed cell death protein 1 (PD-1/PD-1L) which is found on both tumor cells and tumor-infiltrating immune cells. The immune cell infiltration varies between different meningiomas. It contributes to a microenvironment with potential contradictory effects on tumor growth and edema. The immune mechanisms are potential therapeutic targets provided that their effects can be comprehensively understood.


The Republic of Srpska Iodine Deficiency Survey 2006.
A survey related to iodine deficiency in the Republic of Srpska was first conducted in 1999 and resulted in the adoption of regulations concerning the quality of salt for human consumption. In order to reassess iodine status, we conducted the Republic of Srpska Iodine Deficiency Survey in 2006. The survey was conducted in a sample of 1,200 schoolchildren using parameters recommended by WHO, UNICEF and ICCIDD: palpation of thyroid gland, iodine urinary excretion, thyroid utrasonography and content of iodine in salt. The goiter prevalence in the total group indicated mild iodine deficiency in the Republic of Srpska, whereas urinary iodine excretion suggested iodine sufficiency. Only 35.7% of salt samples were adequately iodinated, 51.2% were hypo-iodinated and 13.1% were hyper-iodinated. Of the salt samples tested, 40.9% were iodinated using potassium iodide, despite the fact that this method of salt iodination is forbidden by regulations related to the quality of salt for human consumption. Higher prevalence of goiter and lower urinary iodine content was found in rural areas compared to urban ones, although the iodine content of salt did not differ between these two areas. It seems that the Republic of Srpska has progressed from moderate (1999) to mild iodine deficiency with a wide range in the urinary iodine excretion values. However, the salt for human consumption is of low quality. The higher prevalence of goiter and the lower urinary iodine values in rural areas compared to urban ones may be attributed to differences in salt usage and/or nutritional factors.


Genetic variants in Alzheimer disease - molecular and brain network approaches.
Genetic studies in late-onset Alzheimer disease (LOAD) are aimed at identifying core disease mechanisms and providing potential biomarkers and drug candidates to improve clinical care of AD. However, owing to the complexity of LOAD, including pathological heterogeneity and disease polygenicity, extraction of actionable guidance from LOAD genetics has been challenging. Past attempts to summarize the effects of LOAD-associated genetic variants have used pathway analysis and collections of small-scale experiments to hypothesize functional convergence across several variants. In this Review, we discuss how the study of molecular, cellular and brain networks provides additional information on the effects of LOAD-associated genetic variants. We then discuss emerging combinations of these omic data sets into multiscale models, which provide a more comprehensive representation of the effects of LOAD-associated genetic variants at multiple biophysical scales. Furthermore, we highlight the clinical potential of mechanistically coupling genetic variants and disease phenotypes with multiscale brain models.


Human cerebral spheroids undergo 4-aminopyridine-induced, activity associated changes in cellular composition and microrna expression.
Activity-induced neurogenesis has been extensively studied in rodents but the lack of ante mortem accessibility to human brain at the cellular and molecular levels limits studies of the process in humans. Using cerebral spheroids derived from human induced pluripotent stem cells (iPSCs), we investigated the effects of 4-aminopyridine (4AP) on neuronal activity and associated neurogenesis. Our studies demonstrate that 4AP increases neuronal activity in 3-month-old cerebral spheroids while increasing numbers of new neurons and decreasing the population of new glial cells. We also observed a significant decrease in the expression of miR-135a, which has previously been shown to be decreased in exercise-induced neurogenesis. Predicted targets of miR-135a include key participants in the SMAD2/3 and BDNF pathways. Together, our results suggest that iPSC-derived cerebral spheroids are an attractive model to study several aspects of activity-induced neurogenesis.


Insulin effect on fetal glucose utilization.
Insulin infused into a sheep fetus over a 3-hr period at the rate of approximately 0.24 U.kg-1.h-1 increased fetal glucose uptake (utilization) from 4.4 +/- 0.7 mg.min-1.kg-1 to 6.9 +/- 0.9 mg.min-1.kg-1 as compared to a noninsulin control period. Insulin administration did not alter fetal oxygen consumption (8.6 +/- 0.7 ml.min-1.kg-1 vs. 7.7 +/- 0.7 ml.min-1.kg-1), umbilical blood flow (220 +/- 1 ml.min-1.kg-1 vs. 209 +/- 16 ml.min-1.kg-1), or the placental clearances of antipyrine (114 +/- 7 ml.min-1.kg-1 vs. 109 +/- 8ml.min-1.kg-1) and urea (24.5 +/- 2.2 ml.min-1.kg-1 vs. 25.0 +/- 2.1 ml.min-1.kg-1). Fetal plasma glucose concentration fell significantly (0.22 +/- 0.01 mg.ml-1 to 0.16 +/- 0.01 mg.ml-1) during insulin infusion. The insulin effect on fetal glucose uptake occurred over a range of maternal glucose concentrations (0.32 leads to 0.78 mg.ml-1), which were not altered by the infusion of insulin in the fetal compartment. Insulin has a specific effect on increasing fetal glucose uptake and utilization.


Glutamate-101 is critical for the function of the sodium and chloride-coupled GABA transporter GAT-1.
We have investigated the possible role of selected negatively-charged amino acids of the sodium and chloride-coupled GABA transporter GAT-1 on sodium binding. These residues located adjacent to putative transmembrane domains and which are conserved throughout the large superfamily of neurotransmitter transporters were changed by site-directed mutagenesis. The functional consequences were that one of the residues, glutamate-101, was critical for transport. Its replacement by aspartate left only 1% of the activity, and no activity could be detected when it was replaced by other residues. Expression levels and targeting to the plasma membrane of the mutant transporters appeared normal. Transient sodium currents were not observed in the mutants, and increased sodium concentrations did not affect the percentage of wild type transport of the E101D mutant. It is concluded that residue glutamate-101 is critical for one or more of the conformational changes of GAT-1 during its transport cycle.


Connective Tissue Disease-Associated Pulmonary Interstitial Fibrosis with Mycobacterium Paraintracellulare Infection: a Case Report.
Infectious pulmonary diseases caused by nontuberculous mycobacteria (NTM) are becoming more common in clinical work, and early detection of the bacterium and its early identification are prerequisites for accurate treatment. By reporting a case of confirmed NTM infection in a patient with connective tissue disease-associated interstitial lung fibrosis, a joint literature analysis was performed to improve clinicians' understanding of NTM and the clinical application of targeted next-generation sequencing (tNGS). Chest CT suggested a partially enlarged cavitary lesion in the upper lobe of the right lung, combined with positive sputum antacid staining, and sputum tNGS was sent to confirm the final diagnosis of Mycobacterium paraintracellulare infection. The successful application of tNGS helps in the rapid diagnosis of NTM infection. It also reminds medical practitioners to consider the presence of NTM infection in advance in the presence of many NTM infection factors, combined with imaging manifestations.


Content, face, and construct validity of the Irritable Bowel Syndrome Quality of Life (IBS-QOL) as a measure of bowel-related quality of life in spinal cord injury.
Neurogenic bowel dysfunction is commonly encountered after a spinal cord injury (SCI), leading to a tremendous impact on quality of life (QOL). The neurogenic bowel dysfunction score (NBDS) is commonly used to measure the severity of bowel dysfunction and predict QOL. However, there is no comprehensive instrument to assess bowel-specific QOL for SCI patients. Instead, the Irritable Bowel Syndrome-Quality of Life (IBS-QOL) questionnaire evaluates the impact of bowel dysfunction on several aspects of QOL, although this questionnaire has not been validated for the SCI population. Motivated by the compelling need of instruments to accurately evaluate the QOL in patients who develope NBD after SCI, we aimed to assess the construct, content, and face validity of IBS-QOL in this population. Adult SCI patients with at least 3 months after their injury were recruited from the outpatient clinic of a national rehabilitation hospital. Patients completed the NBDS and IBS-QOL via telephone interview or paper survey in the clinic. Content and face validity were assessed via interviews with professionals with expertise in providing chronic care for SCI, as well as a subgroup of patients. Construct validity was assessed using the hypotheses testing method. Internal consistency was assessed using Cronbach's ⍺. Factor analysis was performed to assess the dimensionality of the IBS-QOL in the SCI population. A total of 106 patients with a median age of 45.5 years (interquartile range: 21-79) participated in the study. The majority of the sample were men (n = 82, 77%) and had endured thoracolumbar injuries (n = 74, 71.2%). Twelve patients (seven English- and five Spanish speakers) and six professionals took part in content/face validation interviews. The median IBS-QOL total score was 15.91/100 (interquartile range: 4.55-33.14). IBS-QOL differentiated the subgroups of patients with severe bowel symptoms in terms of uneasiness, sweating, or headaches during bowel emptying (p = 0.0003), time spent on bowel emptying (p = 0.0065), flatus incontinence (p = 0.0076), and overall satisfaction with bowel function (p < 0.001), demonstrating its adequate construct validity. Interviews with the patients and professionals supported the comprehensiveness, comprehensibility, and relevance of IBS-QOL for assessment of bowel-related QOL in the SCI population. Item-level analysis of professional responses showed that 97% of questions were relevant to the construct and population of interest. Internal consistency analysis yielded a Cronbach's ⍺ of 0.9684. Exploratory factor analysis yielded six underlying factors which cumulatively accounted for 72.21% of the total variance, reflecting the dimensionality of bowel-related QOL in SCI population. IBS-QOL questionnaire is a comprehensive measure of bowel-related QOL which encompasses the concerns of SCI patients. Our findings support the content, face and construct validity of IBS-QOL as a measure of bowel-related QOL in SCI. Further studies are warranted to assess the reliability and responsiveness of IBS-QOL, and to evaluate its performance across different patient populations.


When the endometrioid adenocarcinoma and the endometrial stromal sarcoma meet: A report of an extremely rare case.
Collision tumors are characterized by the coexistence of two adjacent, but histologically distinct tumors. This entity can occur between tumors originating from the same organ or between metastases from other sites. A 49-year-old postmenopausal female with abnormal vaginal bleeding and abdominal pain was diagnosed with two coexistent tumors, a grade 1 endometrioid carcinoma and a pT2 undifferentiated stromal sarcoma (USS). On the first time, the patient underwent a total abdominal hysterectomy with bilateral salpingo-oopherectomy and one month later, she was diagnosed with recurrence. Then, a second surgical excision of the recurrent tumor was performed including exploratory laparotomy and anterior pelvic exenteration. She had an uneventful postoperative period, but unfortunately a month following the second operation she passed away. We aim to raise awareness of these rare synchronous malignancies and highlight the importance of having a broad differential diagnosis in a patient presenting with abnormal vaginal bleeding. Further studies with larger patient populations are needed to shed light in etiology and pathogenesis of the concurrence of two malignancies with different embryological origin in the same organ, in order to optimize management of these patients.


Optimization of pancreatic lipase inhibitory and antioxidant activities of Ilex paraguariensis by using response surface methodology.
Response surface methodology (RSM) using a Box-Behnken design was used to optimize the extraction conditions for obtaining pancreatic lipase inhibitory and antioxidant principles from Ilex paraguariensis leaves. Three influencing factors: extraction time (min), the liquid-solid ratio, and ethanol concentration (%, v/v) were investigated in the ultrasonic extraction process. Optimization of the extraction conditions to obtain a product with minimum PL activity, maximum antioxidant activity, and maximum yield was performed using RSM by focusing on the three target influencing factors. The optimum conditions were established as the ethanol concentration (54.8 %), liquid-solid ratio (35.4), and extraction time (70.0 min). Under these conditions, the 2,2-diphenyl-1-picrylhydrazyl scavenging activity, PL activity, extraction yield were 59.3 ± 3.5, 35.3 ± 3.0, and 34.4 ± 0.4 %, respectively, similar to the theoretical predicted values of 59.7, 35.2, and 34.3 %, respectively.


Organization of the projections from the subiculum to the ventral striatum in the rat. A study using anterograde transport of Phaseolus vulgaris leucoagglutinin.
The projections of the subiculum, as the main output structure of the hippocampal formation, to the striatum were studied in the rat using the anterograde tracer Phaseolus vulgaris leucoagglutinin. It appears that not only the entire nucleus accumbens, part of the so-called ventral striatum, receives fibres from the subiculum, but that the hippocampal projection area in the striatum includes also the most medial, ventral, rostral and caudal parts of the caudate-putamen complex. Moreover, a relatively small number of fibres and terminals are present in the striatal elements of the medial part of the olfactory tubercle. The projections to the ventral and caudal parts of the caudate-putamen are predominantly derived from the ventral subiculum, whereas the projections to the rostral part of the caudate-putamen are derived from the dorsal subiculum. Furthermore, with respect to the subiculum-accumbens pathway a topographical organization could be established. Thus, the ventral or temporal part of the subiculum projects predominantly to the caudomedial part of the nucleus accumbens, and to a lesser degree to its rostromedial portion, whereas progressively more dorsal or septal parts of the subiculum send fibres to successively more lateral and rostral portions of the nucleus accumbens. Very sparse projections are found to the contralateral nucleus accumbens, arranged in a topographical manner similar to the ipsilateral projections. An important observation with respect to the structure of the nucleus accumbens is that the subicular terminations are inhomogeneously distributed, although a relation with earlier described mosaic patterns in the connectivity and neurochemical composition of the nucleus is not yet clear. Subicular fibres have their densest terminations in relatively cell-poor regions of the nucleus accumbens, and in particular tend to avoid small cell clusters.


Melatonin provides neuroprotection in the late-gestation fetal sheep brain in response to umbilical cord occlusion.
Oxygen free radicals, including the highly toxic hydroxyl radical (*OH), initiate lipid peroxidation and DNA/RNA fragmentation and damage cells. The pineal hormone melatonin is an antioxidant and powerful scavenger of *OH. We hypothesized that maternally administered melatonin could reduce *OH formation, lipid peroxidation, and DNA/RNA damage in the fetal brain in response to asphyxia. In 15 fetal sheep, extracellular *OH was measured by microdialysis in white and gray matter of the parasagittal cortex. In 10 fetuses, asphyxia was induced by umbilical cord occlusion for 10 min using an inflatable cuff - the ewes of these fetuses received either intravenous melatonin (1 mg bolus, then 1 mg/h for 2 h; n = 5) or vehicle (1% ethanol in saline; n = 5), and results were compared to fetuses with sham cord occlusion and vehicle-infused ewes (n = 5). Hypoxemia, acidemia, hypertension and bradycardia produced by cord occlusion was similar in the melatonin- and vehicle-treated groups. In the vehicle-treated group, cord occlusion resulted in a significant increase in *OH in gray matter at 8-9.5 h after occlusion (p < 0.05); in contrast, there was no *OH change in the melatonin-treated group. After cord occlusion, lipid peroxidation (4-hydroxynonenal immunoreactivity) found throughout the brain of vehicle-infused ewes was significantly less in the melatonin-infused group. Melatonin had no significant effect on the distribution of DNA/RNA fragmentation, as shown by 8-hydroxydeoxyguanosine immunoreactivity. Thus, brief asphyxia results in significant and delayed entry of *OH into the extracellular space of cortical gray matter in the fetal sheep brain, and melatonin given to the mother at the time of the insult abrogates this increase. Melatonin, in reducing O2 free radical production, may be an effective neuroprotective treatment for the fetus.


Altered Purkinje cell maturation in rats exposed prenatally to ethanol. II. Synaptology.
Pregnant rats of Sprague-Dawley strain were offered a protein- and vitamin-enriched nutritionally balanced liquid ethanol diet, providing 35% of calories as ethanol. Control animals were pair-fed identical liquid diet except that maltose-dextrins were substituted for ethanol. Pups of both ethanol-exposed and pair-fed groups were surrogate-fostered by mothers which received normal rat chow ad libitum. An average of eight pups of each experimental and control group was killed at 0-1, 5, 7, 10, 14, 21, 28, and 42 days. After fixation, their cerebella were bisected in the midvermal plane and one-half embedded in Araldite. Thin sections cut from lobules II/III were stained with uranyl acetate and lead citrate and the synaptology of the Purkinje neurons was studied with the electron microscope in both the experimental and control groups. Impaired climbing fiber maturation was seen in ethanol-exposed pups as evident from the presence of somatic spines--climbing fiber synapses at 14 days postnatally. In the 14-day-old control pups the climbing fiber maturation was complete or nearly complete as evident by their synapses on spines situated on the smooth dendritic branches and by the absence or paucity of climbing fiber--somatic spine synapse. In addition, a reduction in the number of parallel fibers was evident from the increase in Purkinje cell spines per varicosity in the ethanol-exposed pups. We conclude, therefore, a direct or indirect effect of ethanol occurs on climbing fiber maturation and Purkinje cell parallel fiber relationship.


Management of sport-related concussion in young athletes.
Sport-related head injuries are a common clinical problem. Most head injuries in young athletes are mild traumatic brain injuries or concussions. The highest number of sport-related concussions has been reported in American football. In addition to the well described physical and psychosocial growth, there is ongoing neurocognitive development of the brain during childhood and through adolescence. This developmental process has direct implications in the assessment and management of head injuries in young athletes. Research on the management and long-term outcome following brain injuries in young athletes is limited. Traditionally, the assessment of concussion has been based on clinical history and physical and neurological examination. Increasingly, neuropsychological testing, especially computerised testing, is providing objective measures for the initial assessment and follow-up of young athletes following brain injuries. Numerous guidelines have been published for grading and return to play criteria following concussion; however, none of these have been prospectively validated by research and none are specifically applicable to children and adolescents.


Attributes of brain metastases from breast and lung cancer.
Most brain metastases arise from breast and lung cancers. Few studies compare the brain regions they involve, their numbers and intrinsic attributes. Records of all patients referred to Radiation Oncology for treatment of symptomatic brain metastases were obtained. Computed tomography (n = 56) or magnetic resonance imaging (n = 72) brain scans were reviewed. Data from 68 breast and 62 lung cancer patients were compared. Brain metastases presented earlier in the course of the lung than of the breast cancer patients (p = 0.001). There were more metastases in the cerebral hemispheres of the breast than of the lung cancer patients (p = 0.014). More breast than lung cancer patients had cerebellar metastases (p = 0.001). The number of cerebral hemisphere metastases and presence of cerebellar metastases were positively correlated (p = 0.001). The prevalence of at least one metastasis surrounded with >2 cm of edema was greater for the lung than for the breast patients (p = 0.019). The primary tumor type, rather than the scanning method, correlated with differences between these variables. Brain metastases from lung occur earlier, are more edematous, but fewer in number than those from breast cancers. Cerebellar brain metastases are more frequent in breast cancer.


Radiotherapy may augment response to immunotherapy in metastatic uveal melanoma patients.
Uveal melanoma (UM) is a subtype of melanoma arising from the ocular region. Despite various local therapies available, a significant portion of patients develop distant metastases, primarily to the liver. While cutaneous melanoma is very sensitive to immunotherapy, UM is known to be less responsive and patients were excluded from pivotal clinical trials. To date, there is no standard first line therapy for metastatic UM and clinical trial participation is encouraged. While UM is considered a radio-resistant tumor, there is a role for radiotherapy (RT) as palliative treatment and possibly for immune sensitization. This a retrospective analysis aimed at addressing the role of combination checkpoint inhibitors (ICI) with RT as a synergistic treatment in metastatic UM patient. We hypothesized that concurrent RT would improve the clinical response to immunotherapy. Retrospective chart review of patients with metastatic UM treated with ICI at Ella Lemelbaum Institute between 2015 and 2021. Patients' electronic medical records were analyzed for baseline characteristics, response rate and survival data. Patients were grouped according to receipt of concomitant RT. Study was approved by local IRB and statistical analyses done using Stata V.17. Thirty-nine patients were treated with immunotherapy. Fifty percent were treated with anti-programmed cell death (PD)-1 and 50% with anti-PD1- anti CTLA4 combination therapy. Nine patients were treated concomitantly with immunotherapy and external beam RT or with stereotactic body RT (group A) and 29 patients were treated with immunotherapy alone (group B). Overall response rate was significantly higher in group A (44% versus 10%, p = 0.004). Median progression-free survival was longer for patients in group A (22 months versus 3 m, Hazard Ratio (HR) = 0.37, p = 0.036). Median overall survival was also longer for group A (26 months versus 7.5 m, HR = 0.34, p = 0.03). Toxicity was comparable between the groups. RT may improve response to immunotherapy with ICI in metastatic UM patients and may confer an advantage in survival. Further prospective, larger studies are warranted.


Oxidases, carbon nanotubes, and direct electron transfer: A cautionary tale.
The case study of four FAD-dependent oxidase enzymes is presented in the context of the often-claimed direct electron transfer (DET) to glucose oxidase at carbon nanotubes (CNT). The selected enzymes included d-amino acid (AAOx), alcohol (AOx), pyranose (PyOx), and choline oxidase (ChOx). Each enzyme (E) was mixed with chitosan and CNT (either multi- or single-walled) to form a CNT/E film on the surface of glassy carbon electrode. All eight CNT/E films displayed redox activity depicted by voltammetric current peaks near -0.4 V. However, no DET was observed for any of the films as indicated by the absence of expected substrate- and oxygen-induced asymmetry in the anodic-to-cathodic charge ratio. The peaks are suggested to be due to the redox of either a dissociated FAD cofactor, in the case of AAOx and AOx, or denatured enzyme in the case of PyOx and ChOx. The amperometric assays of the films revealed the lowering of enzymatic activity of all four oxidases by CNT. The results are consistent with the hypothesis of oxidase molecules displaying a spectrum of enzymatic activity in CNT/E films ranging from voltammetrically untraceable (for molecules adsorbed on CNT) to amperometrically measurable (for molecules remote from CNT). The kinetic studies showed that enzyme molecules with no net charge leached at the slowest rate from CNT/E films. This work adds to a growing number of reports challenging the fallacy of DET to FAD-dependent native oxidases.


The inhibitory effects of metabolites from Bacillus pumilus on potato virus Y and the induction of early response genes in Nicotiana tabacum.
To develop a new antiviral preparation from a microbial source, the halophilic bacterium Bacillus pumilus E303035 was isolated from a soil sample collected at Qarhan Salt Lake in Qinghai, China. The inhibitory activity of an ethyl acetate extract of its fermentation broth was higher than that of an n-butanol extract. After isolation and purification, 9 compounds were obtained: cyclo(L-Leu-L-Pro) (1), cyclo(L-Pro-L-Tyr) (2), Brevianamide F (3), 2-(3-Indolyl) ethanol (4), N-[2-(1H-indol-3-yl) ethyl] acetamide (5), 3, 3-di(1H-indol-3-yl)propane-1,2-diol (6), Lincomycin B (7), dibutylphthalate (8), and p-hydroxyphenethyl alcohol (9). Compounds 1, 5, and 9 showed inhibitory activities against potato virus Y (PVY). Compounds 1, 4, and 9 had significant inhibitory activity against genes HC-pro, P3, and Nib, compound 5 against gene P3, and compounds 1 and 4 against NIa. Compounds 1, 4, 5, and 9 had significant inhibitory activity against genes VPg and 6K1. Active compounds 1, 5, and 9 had various effects on the expression of viral genes related to pathogenesis. Expression of genes cullin and XTH was up-regulated and CP was down-regulated, compared to the positive control. In conclusion, compounds 1, 5, and 9 might be considered as potential antiviral agents for future development.


High prevalence of differentiated thyroid carcinoma in acromegaly.
Acromegaly is a chronic disease caused by increased GH secretion and associated with a greater risk of developing both benign and malignant tumours. In the present study we evaluated the prevalence of thyroid disorders and thyroid malignancies in a series of acromegalic subjects. We studied, retrospectively, a continuous series of 125 acromegalic patients referred to the Endocrinology Centres at the University Hospitals of Catania and Ferrara, Italy, over a 22-year period. Diagnosis and management of acromegaly were based on standardized criteria. In all patients thyroid function and morphology were evaluated by serum free T4, free T3, TSH measurements and ultrasound scanning, respectively. Fine-needle aspiration biopsy (FNAB) was performed in all solid-mixed thyroid nodules of diameter greater than 1 cm. IGF-1 expression was assessed by semiquantitative immunohistochemical analysis in some patients with differentiated thyroid cancer. Abnormal thyroid function was found in eight cases (6%). A diffuse or nodular goitre was present in 102 cases (82%). Thyroidectomy was performed in 17 patients. Histological examination revealed a differentiated thyroid cancer in seven of the patients. No significant association of thyroid cancer with GH or IGF-1 levels was found. Semiquantitative assessment of IGF-1 expression by immunohistochemistry revealed a more intense staining in thyroid cancer from acromegalic subjects than in papillary thyroid cancer from nonacromegalic subjects. The frequency of thyroid disorders in our series of acromegalic subjects was similar to that previously observed in these patients. However, the prevalence of thyroid cancer was not only strikingly elevated (5.6%) in comparison to the estimated prevalence in the general population (0.093%), but it was even higher than that reported for acromegalic subjects. Sustained exposure to high serum IGF-1 levels is likely to play a role in the development of thyroid cancer in this disease. An additive role for the autocrine/paracrine action of locally produced IGF-1 is also possible. Our results suggest that thyroid function and morphology should be carefully monitored in all acromegalic patients.


Donor age effects on in vitro chondrogenic and osteogenic differentiation performance of equine bone marrow- and adipose tissue-derived mesenchymal stromal cells.
Bone marrow (BM)- and adipose tissue (AT)-derived mesenchymal stromal cells (MSCs) have shown potential as cell-based therapies for cartilage and bone injuries and are used increasingly in human and veterinary practice to facilitate the treatment of orthopedic conditions. However, human and rodent studies have documented a sharp decline in chondrogenic and osteogenic differentiation potential with increasing donor age, which may be problematic for the important demographic of older orthopedic patients. The aim of this study was to identify the effect of donor age on the chondrogenic and osteogenic differentiation performance of equine BM- and AT-MSCs in vitro. BM- and AT-MSCs and dermal fibroblasts (biological negative control) were harvested from horses in five different age groups (n = 4, N = 60); newborn (0 days), yearling (15-17 months), adult (5-8 years), middle-aged (12-18 years), and geriatric (≥ 22 years). Chondrogenic differentiation performance was assessed quantitatively by measuring pellet size, matrix proteoglycan levels, and gene expression of articular cartilage biomarkers. Osteogenic differentiation performance was assessed quantitatively by measuring alkaline phosphatase activity, calcium deposition, and gene expression of bone biomarkers. Chondrogenic and osteogenic differentiation performance of equine BM- and AT-MSCs declined with increasing donor age. BM-MSCs had a higher chondrogenic differentiation performance. AT-MSCs showed minimal chondrogenic differentiation performance in all age groups. For osteogenesis, alkaline phosphatase activity was also higher in BM-MSCs, but BM-MSCs calcium deposition was affected by donor age earlier than AT-MSCs. Chondrogenic and osteogenic differentiation performance of BM-MSCs exhibited a decline as early as between the newborn and yearling samples. Steady state levels of mRNA encoding growth factors, chondrogenic, and osteogenic biomarkers were lower with increasing donor age in both MSC types. The data showed that chondrogenic and osteogenic differentiation performance of equine BM-MSCs declined already in yearlings, and that AT-MSCs showed minimal chondrogenic potential, but were affected later by donor age with regards to osteogenesis (calcium deposition). The results highlight the importance of donor age considerations and MSC selection for cell-based treatment of orthopedic injuries and will help inform clinicians on when to implement or potentially cryopreserve cells. Moreover, the study provides molecular targets affected by donor age.


Modification of cellular efflux and cytotoxicity of adriamycin by biscoclaulin alkaloid in vitro.
The intracellular uptake, retention and cytotoxicity of adriamycin (ADR) combined with a biscoclaulin alkaloid, cepharanthine, were investigated by flow cytometry in NIH 3T3 cells. Cepharanthine suppressed the efflux of ADR in a similar fashion to verapamil. The intracellular uptake and retention of ADR were increased gradually by 0.1 to 1 microgram/ml of cepharanthine and reached a plateau at greater than 1 microgram/ml. Cepharanthine, which had no toxic action on survival, increased intracellular ADR uptake by about 20% for 1 h incubation at 37 degrees C, and increased cellular ADR retention after incubation in an ADR-free medium for 4 h from 15% to 75%. The cytotoxicity of ADR was enhanced 5-fold in the cells pre- and co-incubated with cepharanthine. When cepharanthine was present in the medium before, during and for colony formation (10 days) after incubation with ADR, the cytotoxicity increased to about 300-fold. Furthermore, an increase in intracellular uptake of ADR was induced by an elevated temperature of 43 degrees C, and the efflux of ADR was inhibited by cepharanthine. A high level of intracellular ADR was maintained during the treatment. These results suggest a possible novel use of cepharanthine to improve the drug sensitivity of tumors resistant to ADR.


Milrinone and low cardiac output following cardiac surgery in infants: is there a direct myocardial effect?
We assessed the effect of milrinone on myocardial function in pediatric patients with postoperative low cardiac output syndrome by index of myocardial performance in a prospective, open-label, nonrandomized, consecutive study. Fifteen patients with low cardiac output syndrome following cardiac surgical treatment were studied in the tertiary cardiothoracic pediatric intensive care unit between April 2001 and November 2003 (age range, 0.2-16 months; median, 7; weight, 2.7-11.8 kg; median, 5). Echocardiographic, Doppler-derived, time interval-based index of myocardial performance (Tei index) was used to study cardiac function prior to and while on intravenous milrinone treatment for 18-24 hours. Treatment with milrinone led to improvement in biventricular myocardial function [mean right ventricular index from 0.521 (SD-0.213) to 0.385 (SD-0.215), p = 0.003; mean left ventricular index from 0.636 (SD-0.209) to 0.5 (SD-0.171), p = 0.012). No difference was found in the values of heart rate corrected right or left ventricular ejection time prior to and while on treatment with milrinone (right ventricle: mean, 1.23 (SD-0.42) and 1.14 (SD-0.48), p = 0.29; left ventricles: mean, 1.17 (SD-0.51) and 1.13 (SD-0.48), p = 0.66) Our data support the direct myocardial effect of milrinone as part of the mechanism behind its already proven benefit in children with low cardiac output syndrome following cardiac surgery.


Empower Veterans Program (EVP): a chronic pain management program demonstrates positive outcomes among veterans.
Chronic pain is a highly prevalent health condition among veterans. Traditional pharmacological interventions present unique challenges for chronic pain management including prescription opioid addiction and overdose. In alignment with the 2016 Comprehensive Addiction and Recovery Act and VA's Stepped Care Model to meet veterans' pain management needs, the Offices of Rural Health and Pain Management, Opioid Safety, and Prescription Drug Monitoring Program (PMOP) funded an enterprise-wide initiative to implement a Step 3 integrated tele-pain program: Empower Veterans Program (EVP). EVP provides veterans with chronic pain self-care skills using a whole health driven approach to pain management. The Comprehensive Addiction and Recovery Act prompted the strategic approach to offer non-pharmacological options to meet veterans' pain management needs. EVP, a 10-week interdisciplinary group medical appointment, leverages Acceptance and Commitment Therapy, Mindful Movement, and Whole Health to provide veterans with chronic pain self-care skills. This evaluation was conducted to describe participant characteristics, graduation, and satisfaction rates; and assess pre-post patient-reported outcomes (PRO) associated with EVP participation. A sample of 639 veterans enrolled in EVP between May, 2015 and December, 2017 provided data to conduct descriptive analyses to assess participant demographics, graduation, and satisfaction rates. PRO data were analyzed using a within-participants pre-post design, and linear mixed-effects models were used to examine pre-post changes in PRO. Of 639 participants, 444 (69.48%) graduated EVP. Participant median program satisfaction rating was 8.41 (Interquartile Range: 8.20-9.20). Results indicate pre-post EVP improvements (Bonferroni-adjusted p < .003) in the three primary pain outcomes (intensity, interference, catastrophizing), and 12 of 17 secondary outcomes, including physical, psychological, health-related quality of life (HRQoL), acceptance, and mindfulness measures. Data suggest that EVP has significant positive outcomes in pain, psychological, physical, HRQoL, acceptance, and mindfulness measures for veterans with chronic pain through non-pharmacological means. Future evaluations of intervention dosing effect and long-term effectiveness of the program is needed.


Socioeconomic disparity in inpatient mortality after traumatic injury in adults.
Prior studies have demonstrated that race and insurance status predict inpatient trauma mortality, but have been limited by their inability to adjust for direct measures of socioeconomic status (SES) and comorbidities. Our study aimed to identify whether a relationship exists between SES and inpatient trauma mortality after adjusting for known confounders. Trauma patients aged 18-65 years with an Injury Severity Scores (ISS) of ≥9 were identified using the 2003-2009 Nationwide Inpatient Sample. Median household income (MHI) by zip code, available by quartiles, was used to measure SES. Multiple logistic regression analyses were performed to determine odds of inpatient mortality by MHI quartile, adjusting for ISS, type of injury, comorbidities, and patient demographics. In all, 267,621 patients met inclusion criteria. Patients in lower wealth quartiles had significantly greater unadjusted inpatient mortality compared with the wealthiest quartile. Adjusted odds of death were also higher compared with the wealthiest quartile for Q1 (odds ratio [OR], 1.13; 95% confidence interval [CI], 1.06-1.20), Q2 (OR, 1.09; 95% CI, 1.02-1.17), and Q3 (OR, 1.11; 95% CI, 1.04-1.19). MHI predicts inpatient mortality after adult trauma, even after adjusting for race, insurance status, and comorbidities. Efforts to mitigate trauma disparities should address SES as an independent predictor of outcomes.


Prevalence and genotype-phenotype correlations of GBA-related Parkinson disease in a large Chinese cohort.
Variants in the glucocerebrosidase (GBA) gene are recognized as a common and important genetic risk factor for Parkinson disease (PD). However, the impact of variant severity on the clinical phenotype of PD in the Chinese population remains unclear. Thus, the present study aimed to determine the frequency of GBA-related PD (GBA-PD) and the relationship of GBA variant severity with clinical characteristics in a large Chinese cohort. Long-range polymerase chain reaction and next generation sequencing were performed for the entire GBA gene. GBA variant severity was classified into five classes: mild, severe, risk, complex, and unknown. Among the total 737 PD patients, 47 GBA variants were detected in 79 (10.72%) patients, and the most common GBA variants were R163Q, L444P, and R120W. Complete demographic and clinical data were obtained for 673 patients, which revealed that 18.50% of early onset PD patients had GBA variants. Compared with patients without GBA variants, GBA-PD patients experienced PD onset an average of 4 years earlier and had more severe motor and nonmotor symptoms. Patients carrying severe and complex variants had a higher burden of nonmotor symptoms, especially depression, and more mood/cognitive and gastrointestinal symptoms than patients carrying mild variants. GBA-PD is highly prevalent in the Chinese population. The severity of GBA variants underlies distinct phenotypic spectrums, with PD patients carrying severe and complex variants seeming to have similar phenotypes. PD patient stratification by GBA variant severity should become a prerequisite for selecting specific treatments.


Vascular cognitive impairment.
Vascular cognitive impairment (VCI) is a term used to capture the entire spectrum of cognitive impairment from mild to more severe forms and includes all forms of stroke (e.g., ischemic and hemorrhagic forms) associated and underlying cognitive impairment related with subclinical vascular brain injury. Vascular contributions to cognitive impairment are common, especially as one ages. Therefore, both stroke and Alzheimer's disease may be important causes of cognitive impairment in later life, and the concomitant occurrence of these disorders may synergize to increase the risk of poor cognition in later life. In this review we discuss the definition and clinical presentation, mechanisms, cardiovascular risk factors and possible prevention and treatment of VCI. VCI is a potentially treatable and preventable cause of cognitive impairment in later life, and familiarity with this condition will help the practitioner provide better care to patients.


Enzyme immunoassay for feline oncornavirus-associated cell membrane antigen (FOCMA) and detection of FOCMA in cell extract by enzyme immunoassay inhibition test.
An enzyme immunoassay (EIA) for FOCMA has been developed. The assay uses alkaline phosphatase-conjugated rabbit anti-cat IgG as the second antibody and p-nitrophenyl phosphate as the substrate for the enzyme to detect cat FOCMA antibody bound to the target cells. In comparison with the indirect immunofluorescence (IIF) test, which was originally used for FOCMA assay, our results showed a good correlation between the two methods. The EIA gives a more objective measure of FOCMA reactivity than does IIF. FOCMA was successfully extracted from FOCMA-positive cell membranes by 0.5% Triton X-100 and further fractionated by ammonium sulfate. The FOCMA activity was assayed by IIF and EIA inhibition test. Most of the FOCMA activity was found in the fractions precipitated by 30% and 50% ammonium sulfate saturation.


The piriform cortex is not a direct olfactory relay to the mediodorsal thalamic nucleus in cats and rabbits.
Following injections of horseradish peroxidase into the mediodorsal thalamic nucleus (MD), retrogradely labeled cells were found in various areas in the cat and rabbit. Among these, olfactory-related areas to which the olfactory bulb projects directly or indirectly via the piriform cortex were the olfactory tubercle, amygdala and insular cortex, while no labeled cells were detected in the piriform cortex and endopiriform nucleus in both species. These results indicate that the piriform cortex and endopiriform nucleus do not send their axons directly to the MD.


A Y chromosome gene family with RNA-binding protein homology: candidates for the azoospermia factor AZF controlling human spermatogenesis.
We have previously mapped the human azoospermia factor to a deletion in Y chromosome interval 6 (subinterval XII-XIV). We now report the isolation and characterization of a gene family located within this deletion. Analysis of the predicted protein products suggests a possible role in RNA processing or translational control during early spermatogenesis. The Y chromosome RNA recognition motif (YRRM) family includes a minimum of three members expressed specifically in the testis. Interphase in situ results and Southern blot analysis indicate that several further YRRM sequences map within interval 6. Several mammalian species show Y chromosome conservation of YRRM sequences. We have detected deletions of YRRM sequences in two oligospermic patients with no previously detectable mutation.


Disseminated Pneumocystis carinii infection in a hemophiliac patient with acquired immunodeficiency syndrome.
A case of disseminated Pneumocystis carinii (PC) infection in a 28-year-old Japanese male hemophiliac with acquired immunodeficiency syndrome (AIDS) is reported. The patient had displayed a high fever and diffuse faint interstitial infiltrates on chest X-ray films without dyspnea three months before his death. At that time, no PC was detected after four consecutive induced sputum tests. Serum anti-cytomegalovirus (CMV) IgM was positive by EIA. No treatment for PC and CMV was given at the patient's request. Autopsy findings disclosed disseminated PC infection consisting of granulomas with caseation-like necrosis and frothy exudate in the lungs and disseminated organized calcification in the blood vessels of extrapulmonary organs. PC cysts and/or trophozoites were detected in these lesions.


The impact of chronic obstructive pulmonary disease on hospitalization and mortality in patients with heart failure.
Several studies have suggested that chronic obstructive pulmonary disease (COPD) could be predictive of the prognosis in patients with heart failure (HF), but yield conflicting findings. Therefore, we conducted a meta-analysis to examine the impact of COPD on adverse outcomes in patients with HF. We systematically searched the databases of PubMed, EMBASE, Google Scholar, Cochrane library from inception to August 2020 for the relevant studies. Adjusted risk ratios (RRs) and confidence intervals (CIs) were collected and then pooled by the Review Manager version 5.30 software with a random-effects model. A total of 18 studies (6 post hoc analyses of trials and 12 observational studies) were included in this meta-analysis. COPD was associated with an increased risk of all-cause mortality (hospitalized HF: RR 1.43, 95% CI: 1.20-1.70; chronic HF: RR 1.24, 95% CI: 1.16-1.33), but not cardiovascular mortality, in patients with hospitalized HF or chronic HF. In addition, COPD was associated with increased risks of all-cause hospitalization (RR 1.31, 95% CI: 1.21-1.42) and HF hospitalization (RR 1.31, 95% CI: 1.21-1.42) in the chronic HF patients. COPD comorbidity could increase the risk of all-cause mortality of HF patients. Future research should confirm the findings on hospitalization because of the limited studies included for this outcome.


Revisiting the East-West advancement flap: great for multiple anatomic locations.
The east-west advancement flap is a simple flap traditionally used to repair Mohs surgery defects on the nose. We aim to demonstrate this flap can be used with good cosmetic outcome and minimal complications on a variety of anatomical sites. This study was a case series of four patients taking place between March 2021 and September 2021 with 4- to 6-week postoperative follow-up. Four male patients were included in the study. Repair sites included the helix, chin, wrist, and scalp. All patients and the Mohs surgeon reported satisfaction with the cosmetic outcome at 4- to 6-week postoperative follow-up with no complications. The east-west advancement flap is a viable repair option for Mohs surgery defects on a variety of anatomical sites.


Vitamins as regulators of calcium-containing kidney stones - new perspectives on the role of the gut microbiome.
Calcium-based kidney stone disease is a highly prevalent and morbid condition, with an often complicated and multifactorial aetiology. An abundance of research on the role of specific vitamins (B6, C and D) in stone formation exists, but no consensus has been reached on how these vitamins influence stone disease. As a consequence of emerging research on the role of the gut microbiota in urolithiasis, previous notions on the contribution of these vitamins to urolithiasis are being reconsidered in the field, and investigation into previously overlooked vitamins (A, E and K) was expanded. Understanding how the microbiota influences host vitamin regulation could help to determine the role of vitamins in stone disease.


Application of pressure-modulated differential scanning calorimetry to the determination of relaxation kinetics of multilamellar lipid vesicles.
We report an extension of the recently published PMDSC method that permitted synchronous determination of heat capacity and expansibility when using slow, defined pressure formats in a DSC scan. Here we applied continuously opposing pressure changes that are fast compared to the time constants of the DSC instrument to study relaxation kinetics of phospholipids. Investigations of multilamellar vesicles of DPPC or DSPC in water revealed for both lipids relaxation times of about 30 s at the maximum of the main transition peak and about 15 s at the maximum of the pretransition. The relaxation times in the transition range are proportional to heat capacity of main- and pretransition. The molecular origin of the relaxation processes appears to stem from pressure-induced water fluxes between the interbilayer region and the bulk water phase.


Mutagenicity of chamuvaritin: a benzyldihydrochalcone isolated from a medicinal plant.
The mutagenic effects of chamuvaritin, dihydrobenzylchalcone isolated from Uvaria chamae, were investigated using Salmonella typhimurium tester strains TA92, TA94--98, TA100--1535, TA1537 and TA1538. The phytochemical was mutagenic in tester strains TA98 and TA100 and required activation by the hepatic S-9 microsomal enzyme preparation.


Miniaturized V-band circularly polarized leaky-wave antenna with continuous radiation coverage using modified waveguide and metasurface CSRRs.
A miniaturized V-band leaky-wave antenna (LWA) with circular polarization and backward-broadside-forward radiation based on a modified half-mode substrate integrated waveguide (M-HMSIW) is presented. The proposed M-HMSIW structure employs broadside coupled complementary split ring resonators to replace metallic vias, resulting in low-cost and fully-planar fabrication advantages over conventional HMSIWs. Each unit cell of the proposed LWA consists of an M-HMSIW in combination with two horizontal stubs and a cross-shaped complementary electric LC slot to provide a proper circular polarization with a composite right/left-handed property. Using this structure, the balanced condition can be obtained for the unit cell; hence a continuous backward-to-forward scanning, including broadside, is achieved. As a result, the proposed LWA with a radiator length of only 3.8 λ0 provides wide-angle beam scanning from - 53° to + 54° over the frequency range of 61.2 GHz to 73.4 GHz, while maintaining an excellent circular polarization between - 25° and 25°. The maximum gain of the LWA is 11.1 dB which is satisfactory, considering its compactness. The antenna's performance is experimentally verified, and close agreement between the simulations and measurements is observed.


Role of glucocorticoid in excretion of an acute potassium load in patients with Addison's disease and panhypopituitarism.
Glucocorticoid (GC) has been shown to stimulate potassium (K) excretion in various conditions, but it is still incompletely resolved whether its presence is essential for the normal K homeostasis. We addressed this question in patients with selective GC deficiency (panhypopituitarism) and with combined GC and mineralocorticoid deficiency (Addison's disease), studied 24 hours after withdrawal of their regular substitution therapy. Compared to data in healthy subjects, both basal K excretion and the kaliuresis after a KCl load (1 mmol/kg body wt orally) were impaired in either patient group (P < 0.05). Physiological cortisol supplementation (20 mg 3 hr prior to test, and 1 mg/hr during test) increased basal K excretion (from 10.6 +/- 1.8 to 19.2 +/- 1.9 mmol/5 hr, P < 0.01) and KCl stimulated kaliuresis (from 47.9 +/- 6.1 to 54.8 +/- 4.7 mmol/5 hr, P = 0.06) to normal levels in panhypopituitarism. Cortisol also improved basal K excretion (from 10.2 +/- 1.5 to 16.9 +/- 3.5 mmol/5 hr, P < 0.05) and KCl-stimulated K excretion (from 31.6 +/- 2.5 to 45.2 +/- 3.8 mmol/5 hr, P < 0.05) in Addison's disease, although KCl-stimulated K excretion remained below normal (P < 0.01). The effects of cortisol on sodium excretion differed between the two patient groups (P < 0.05) in that only in Addison's disease the improved K excretion was associated with sodium retention. Additional experiments with the purely GC compound dexamethasone (0.5 mg 3 hr prior to test, and 0.03 mg/hr during test) in the patients with Addison's disease also improved K excretion (P < 0.05), but without the concomitant sodium retention observed after cortisol.(ABSTRACT TRUNCATED AT 250 WORDS)


Usage of blood products in multiple-casualty incidents: the experience of a level I trauma center in Israel.
To predict how much blood will be needed based on the number of injured patients arriving after a multiple-casualty incident. A retrospective study evaluating data collected in 18 consecutive terrorist attacks in the city of Tel Aviv between January 1997 and February 2005. A large, urban trauma center. A total of 986 patients in 18 events. Number of packed red blood cell (PRBC) units transfused per patient. A total of 332 U of PRBCs were transfused. Half of the PRBC units were administered as massive transfusions to 4.7% of the patients. The number of PRBC units transfused per patient index (PPI) was related to incident size (mean [SD], 0.70 [1.60] to 1.50 [1.60]). The most frequent major blood group transfused was type O (50%). Half of the units of PRBCs were supplied during the first 2 hours. One unit of blood per evacuated victim is sufficient in a small multiple-casualty incident and 2 U is sufficient in a large multiple-casualty incident. Half of the PRBC units should be blood group O.