Skeletal muscle as a molecular and cellular biomarker of disease progression in amyotrophic lateral sclerosis: a narrative review.
Amyotrophic lateral sclerosis is a fatal multisystemic neurodegenerative disease with motor neurons being a primary target. Although progressive weakness is a hallmark feature of amyotrophic lateral sclerosis, there is considerable heterogeneity, including clinical presentation, progression, and the underlying triggers for disease initiation. Based on longitudinal studies with families harboring amyotrophic lateral sclerosis-associated gene mutations, it has become apparent that overt disease is preceded by a prodromal phase, possibly in years, where compensatory mechanisms delay symptom onset. Since 85-90% of amyotrophic lateral sclerosis is sporadic, there is a strong need for identifying biomarkers that can detect this prodromal phase as motor neurons have limited capacity for regeneration. Current Food and Drug Administration-approved therapies work by slowing the degenerative process and are most effective early in the disease. Skeletal muscle, including the neuromuscular junction, manifests abnormalities at the earliest stages of the disease, before motor neuron loss, making it a promising source for identifying biomarkers of the prodromal phase. The accessibility of muscle through biopsy provides a lens into the distal motor system at earlier stages and in real time. The advent of "omics" technology has led to the identification of numerous dysregulated molecules in amyotrophic lateral sclerosis muscle, ranging from coding and non-coding RNAs to proteins and metabolites. This technology has opened the door for identifying biomarkers of disease activity and providing insight into disease mechanisms. A major challenge is correlating the myriad of dysregulated molecules with clinical or histological progression and understanding their relevance to presymptomatic phases of disease. There are two major goals of this review. The first is to summarize some of the biomarkers identified in human amyotrophic lateral sclerosis muscle that have a clinicopathological correlation with disease activity, evidence of a similar dysregulation in the SOD1G93A mouse during presymptomatic stages, and evidence of progressive change during disease progression. The second goal is to review the molecular pathways these biomarkers reflect and their potential role in mitigating or promoting disease progression, and as such, their potential as therapeutic targets in amyotrophic lateral sclerosis.


The phenotypic spectrum in patients with arginine to cysteine mutations in the COL2A1 gene.
The majority of COL2A1 missense mutations are substitutions of obligatory glycine residues in the triple helical domain. Only a few non-glycine missense mutations have been reported and among these, the arginine to cysteine substitutions predominate. To investigate in more detail the phenotype resulting from arginine to cysteine mutations in the COL2A1 gene. The clinical and radiographic phenotype of all patients in whom an arginine to cysteine mutation in the COL2A1 gene was identified in our laboratory, was studied and correlated with the abnormal genotype. The COL2A1 genotyping involved DHPLC analysis with subsequent sequencing of the abnormal fragments. Six different mutations (R75C, R365C, R519C, R704C, R789C, R1076C) were found in 11 unrelated probands. Each mutation resulted in a rather constant and site-specific phenotype, but a perinatally lethal disorder was never observed. Spondyloarthropathy with normal stature and no ocular involvement were features of patients with the R75C, R519C, or R1076C mutation. Short third and/or fourth toes was a distinguishing feature of the R75C mutation and brachydactyly with enlarged finger joints a key feature of the R1076C substitution. Stickler dysplasia with brachydactyly was observed in patients with the R704C mutation. The R365C and R789C mutations resulted in classic Stickler dysplasia and spondyloepiphyseal dysplasia congenita (SEDC), respectively. Arginine to cysteine mutations are rather infrequent COL2A1 mutations which cause a spectrum of phenotypes including classic SEDC and Stickler dysplasia, but also some unusual entities that have not yet been recognised and described as type II collagenopathies.


[Experimental study on lymphatic spread in subcutaneously inoculated cancer with special reference to surgery and nutrition].
Two strains of ascitic tumor (AH109A, AH272 ) were subcutaneously injected into the foot of normally feed and protein deficient rats to study lymphatic spread of cancer. Survival and incidence of lymphatic metastases were determined following surgery for tumor-inoculated rats. In the normally fed rats, tumor cells were always demonstrated in popliteal lymph nodes 2 hours after AH109A inoculation. Sixty-seven percent survival was obtained in the control rats with amputation of the foot 2 hours after AH109A inoculation whereas 100% survival was obtained in the protein deficient rats with the similar treatment. Moreover 100% survival was achieved in both groups when foot amputation with popliteal lymphadenectomy was performed. On the other hand, no survival was obtained, and obvious distant lymph nodes metastases were observed in the rats in which the popliteal lymph node was excised prior to AH109A inoculation. Similar results were obtained after surgery in the AH272 inoculated rats. These findings suggest that the regional lymph nodes serve as a mechanical and functional barrier against the early spread of cancer cells within the lymphatic systems.


Understanding the phase behavior of a protobiomembrane.
The rich thermotropic behavior of lipid bilayers is addressed using phenomenological theory informed by many experiments. The most recent experiment not yet addressed by theory has shown that the tilt modulus in DMPC lipid bilayers decreases dramatically as the temperature is lowered toward the main transition temperature T_{M}. It is shown that this behavior can be understood by introducing a simple free energy functional for tilt that couples to the area per molecule. This is combined with a chain melting free energy functional in which the area is the primary order parameter that is the driver of the main transition. Satisfactory agreement with experiment is achieved with values of the model parameters determined by experiments, but the transition is directly into the gel phase. The theory is then extended to include the enigmatic ripple phase by making contact with the most recent experimentally determined ripple structure.


Modeling livestock population structure: a geospatial database for Ontario swine farms.
Infectious diseases in farmed animals have economic, social, and health consequences. Foreign animal diseases (FAD) of swine are of significant concern. Mathematical and simulation models are often used to simulate FAD outbreaks and best practices for control. However, simulation outcomes are sensitive to the population structure used. Within Canada, access to individual swine farm population data with which to parameterize models is a challenge because of privacy concerns. Our objective was to develop a methodology to model the farmed swine population in Ontario, Canada that could represent the existing population structure and improve the efficacy of simulation models. We developed a swine population model based on the factors such as facilities supporting farm infrastructure, land availability, zoning and local regulations, and natural geographic barriers that could affect swine farming in Ontario. Assigned farm locations were equal to the swine farm density described in the 2011 Canadian Census of Agriculture. Farms were then randomly assigned to farm types proportional to the existing swine herd types. We compared the swine population models with a known database of swine farm locations in Ontario and found that the modeled population was representative of farm locations with a high accuracy (AUC: 0.91, Standard deviation: 0.02) suggesting that our algorithm generated a reasonable approximation of farm locations in Ontario. In the absence of a readily accessible dataset providing details of the relative locations of swine farms in Ontario, development of a model livestock population that captures key characteristics of the true population structure while protecting privacy concerns is an important methodological advancement. This methodology will be useful for individuals interested in modeling the spread of pathogens between farms across a landscape and using these models to evaluate disease control strategies.


Nervus medianus evoked potentials and bispectral index during repeated transitions from consciousness to unconsciousness.
We investigated the relationship between median nerve somatosensory evoked potentials (SSEPs) and the bispectral index (BIS) during alternating periods of consciousness and propofol-induced unconsciousness. Loss of consciousness (LOC) was repetitively induced by bolus injections of propofol in 24 patients undergoing elective surgery in spinal anaesthesia. SSEP and the BIS were recorded during LOC and recovery of consciousness (ROC). The level of consciousness was clinically assessed by the observer's assessment of alertness/sedation scale. Propofol venous plasma concentrations were measured simultaneously. At LOC, all SSEPs latency components were prolonged (P<0.001), whereas amplitudes of the components > or = 45 ms were smaller (P=0.008) and the BIS values were lower (P<0.001). None of the EEG variables regained baseline levels during ROC. Regression analyses revealed that the SSEP components (five latencies and five amplitudes) explained 33% of the variance when predicting ROC; the BIS explained 12%. The combination of SSEP and BIS explained 37% of variance in this patient sample. Propofol venous plasma concentration was 1.2 (0.8) microg ml(-1) during LOC and 0.4 (0.5) microg ml(-1) during ROC. The present results indicate the usefulness of combining variables of the evoked and spontaneous EEG to measure different levels of consciousness, because the SSEP provide additional information beyond the BIS. Inter-individual variability of all the EEG variables limits their predictive potency of ROC after propofol infusion.


Genetically diverse coronaviruses in captive bird populations in a Brazilian zoological park.
This study aimed to investigate the occurrence of coronaviruses (CoVs) in captive birds placed inside a zoological park in Brazil. The role of captive birds in the epidemiology of CoVs in the tropics is poorly understood. A total of 25 (n=25) different species were tested for viral RNA using individual fecal samples collected from healthy birds. Reverse transcription-polymerase chain reaction targeting the 3' untranslated region was used to detect CoV RNA, and positive samples were submitted for sequence analysis. The phylogenetic search revealed nine mutations in the black shouldered peafowl (Pavus cristatus) CoV sequence, which clustered separately from samples previously described in England. This is the first report on the detection of the CoV genome in captive birds in Brazil.


Shaking Up Biotech/Pharma: Can Cues Be Taken from the Tech Industry?
The biotech and pharma (biotech/pharma) industry is in dire need of finding ways to increase efficacy, efficiency, and affordability of its products. The information and technology industry ("tech") industry, which is an industry similarly founded on inventions and innovation, may provide some food for thought. This perspective will demonstrate the shift that biotech/pharma is already making and will propose that the industry has an opportunity to compel change by adopting some aspects of the tech industry with regards to models for technology/product development and leadership attributes.


Binding of scandium ions to metalloporphyrin-flavin complexes for long-lived charge separation.
A porphyrin-flavin-linked dyad and its zinc and palladium complexes (MPor-Fl: 2-M, M=2 H, Zn, and Pd) were newly synthesized and the X-ray crystal structure of 2-Pd was determined. The photodynamics of 2-M were examined by femto- and nanosecond laser flash photolysis measurements. Photoinduced electron transfer (ET) in 2-H2 occurred from the singlet excited state of the porphyrin moiety (H2 Por) to the flavin (Fl) moiety to produce the singlet charge-separated (CS) state (1) (H2 Por(.+) -Fl(.-) ), which decayed through back ET (BET) to form (3) [H2 Por]*-Fl with rate constants of 1.2×10(10) and 1.2×10(9) s(-1) , respectively. Similarly, photoinduced ET in 2-Pd afforded the singlet CS state, which decayed through BET to form (3) [PdPor]*Fl with rate constants of 2.1×10(11) and 6.0×10(10) s(-1) , respectively. The rate constant of photoinduced ET and BET of 2-M were related to the ET and BET driving forces by using the Marcus theory of ET. One and two Sc(3+) ions bind to the flavin moiety to form the Fl-Sc(3+) and Fl-(Sc(3+) )2 complexes with binding constants of K1 =2.2×10(5) M(-1) and K2 =1.8×10(3) M(-1) , respectively. Other metal ions, such as Y(3+) , Zn(2+) , and Mg(2+) , form only 1:1 complexes with flavin. In contrast to 2-M and the 1:1 complexes with metal ions, which afforded the short-lived singlet CS state, photoinduced ET in 2-Pd⋅⋅⋅Sc(3+) complexes afforded the triplet CS state ((3) [PdPor(.+) -Fl(.-) (Sc(3+) )2 ]), which exhibited a remarkably long lifetime of τ=110 ms (kBET =9.1 s(-1) ).


Surgical aspects of decompression craniectomy in malignant stroke: review.
Space-occupying malignant stroke of the middle cerebral artery (MCA) is associated with a high mortality rate of up to 80% under conservative treatment. Although there is convincing evidence that decompression craniectomy can significantly reduce mortality rate and improve neurological outcome in young patients (<60 years), many surgeons are still hesitant to recommend hemicraniectomy for stroke patients. This review addresses some major issues that appear to be an obstacle to decompression craniectomy, in particular, indicating surgery for patients >60 years or with infarcts of the dominant hemisphere. Furthermore, it emphasizes technical issues such as timing and size of the craniectomy, additional temporal lobectomy, and resection of the temporal muscle, as well as duraplasty and cranioplasty. According to the current literature, decompression craniectomy in older patients can increase survival without most severe disabilities, although, most survivors need assistance in most bodily needs. Involvement of the dominant hemisphere results in aphasia that might partly recover in younger patients, although, considering the neuropsychological deficits caused by infarctions of the nondominant hemisphere, involvement of the dominant hemisphere does not pose as a contraindication for decompression craniectomy. Furthermore, there is convincing evidence that surgery should be performed within 48 h after the onset of symptoms and the size of the craniectomy should be at least 12 cm as a minimum. An additional lobectomy or the resection of the temporal muscle, however, can only be part of individual treatment options. Conceding the weak evidence, it is recommended to close the dura by some form of a duraplasty avoiding cerebrospinal fluid leakages or scarring between the cortex and the scalp leading to injuries during reimplantation of the bone-flap. Complications associated with decompression surgery (hemorrhages, infections, 'sinking skin-flap syndrome', cerebrospinal fluid leakages, hydrocephalus, seizures), with the infarction itself, or with those that occur during the ICU course (cardiac and pulmonary complications) appear acceptable and are mostly treatable, especially considering the fatal course of conservative treatment. Key Message: This review summarizes the current state of the literature about decompression craniectomy of patients with malignant stroke addressing, in particular, critical surgical issues, and thus, help surgeons to make decisions confidently for/or against performing surgery.


Variations in Cardiac Arrest Regionalization in California.
The development of cardiac arrest centers and regionalization of systems of care may improve survival of patients with out-of-hospital cardiac arrest (OHCA). This survey of the local EMS agencies (LEMSA) in California was intended to determine current practices regarding the treatment and routing of OHCA patients and the extent to which EMS systems have regionalized OHCA care across California. We surveyed all of the 33 LEMSA in California regarding the treatment and routing of OHCA patients according to the current recommendations for OHCA management. Two counties, representing 29% of the California population, have formally regionalized cardiac arrest care. Twenty of the remaining LEMSA have specific regionalization protocols to direct all OHCA patients with return of spontaneous circulation to designated percutaneous coronary intervention (PCI)-capable hospitals, representing another 36% of the population. There is large variation in LEMSA ability to influence inhospital care. Only 14 agencies (36%), representing 44% of the population, have access to hospital outcome data, including survival to hospital discharge and cerebral performance category scores. Regionalized care of OHCA is established in two of 33 California LEMSA, providing access to approximately one-third of California residents. Many other LEMSA direct OHCA patients to PCI-capable hospitals for primary PCI and targeted temperature management, but there is limited regional coordination and system quality improvement. Only one-third of LEMSA have access to hospital data for patient outcomes.


Giant primary liposarcoma of the mediastinum: A case report and review of the literature.
Liposarcoma is a carcinomatous mesenchymal tumor with various histologic features and is the most common soft tissue sarcoma originating in adipose tissue. Liposarcoma commonly occurs in the lower extremities and retroperitoneum but rarely in the mediastinum, specially extending into the thoracic cavity. We report a giant primary liposarcoma of the posterior mediastinum in a 63-year-old female who complained of cough, sputum, and pain in the right chest wall. A computed tomography scan of the chest showed a giant mass of 24 × 15 × 24 cm in the posterior mediastinum of the right thoracic cavity. After a thorough examination, no suspected lipomatous lesions were found elsewhere in the patient's body. The patient underwent a thoracotomy to remove the mediastinal mass through a right thoracic approach. Subsequently, hematoxylin-eosin staining revealed dedifferentiated liposarcoma (DDL), immunohistochemistry showed positive expression of cyclin-dependent kinase 4, and murine double minute 2 (MDM2), in addition, fluorescence in situ hybridization for the MDM2 gene was also positive, which suggested DDL. The patient was discharged without any complications, and no metastasis or recurrence was observed after 19 months of follow-up. To provide a reference for clinical diagnosis and treatment, we reviewed and discussed the literature on primary liposarcoma of the mediastinum.


PCNL vs RIRS in management of stones in calyceal diverticulum: outcomes from a global multicentre match paired study that reflects real world practice.
Calyceal diverticulum (CD) is the outpouching of a calyx into the renal parenchyma, connected by an infundibulum. Often associated with recurrent stones, common surgical options include percutaneous nephrolithotomy (PCNL) or retrograde intrarenal surgery (RIRS). We aim to present the real-world practises and outcomes comparing both approaches and the technical choices made. Retrospective data including 313 patients from 11 countries were evaluated. One hundred and twenty-seven underwent mini-PCNL and one hundred and eighty-six underwent RIRS. Patient demographics, perioperative parameters, and outcomes were analysed using either T test or Mann-Whitney U test. Categorical data between groups were analysed using the Chi-squared test. Propensity score matching (PSM) was performed matching for baseline characteristics. Subgroup analyses for anomalous/malrotated kidneys and difficult diverticulum access were performed. After PSM, 123 patients in each arm were included, with similar outcomes for stone-free rate (SFR) and complications (p < 0.001). Hospitalisation was significantly longer in PCNL. Re-intervention rate for residual fragments (any fragment > 4 mm) was similar. RIRS was the preferred re-intervention for both groups. Intraoperative bleeding was significantly higher in PCNL (p < 0.032) but none required transfusion. Two patients with malrotated anatomy in RIRS group required transfusion. Lower pole presented most difficult access for both groups, and SFR was significantly higher in difficult CD accessed by RIRS (p < 0.031). Laser infundibulotomy was preferred for improving diverticular access in both. Fulguration post-intervention was not practised. The crux lies in identification of the opening and safe access. Urologists may consider a step-up personalised approach with a view of endoscopic combined approach where required.


Ontogeny of cationic amino acid transport systems in rat placenta.
Gestational regulation of the placental transfer of amino acids from maternal to fetal circulations is essential for the proper development of the fetus. The cationic amino acid transport systems of the microvillous (maternal facing) and basal (fetal facing) membranes of the rat placental syncytiotrophoblast were examined. Inhibition analysis documented the presence of three kinetically distinct cationic amino acid transport mechanisms: a single Na(+)-dependent mechanism in the microvillous membrane, which increased in activity from 14 to 20 days gestation but was absent from the basal membrane throughout the entire gestational period (system Bo,+), and two Na(+)-independent transport systems in both membrane domains, one that is completely inhibited by leucine, which increased in activity in both the microvillous and basal membrane domains, and the other that is leucine insensitive, which remained fairly constant in the basal membrane and increased throughout gestation in the microvillous membrane (system y1+). Northern analysis with the system y1+ cDNA revealed a specific band of approximately 7.4-7.9 kb, which increased with increasing gestational age.


Studies in renal preservation using a rat kidney transplant model: II. The effect of reflushing with citrate.
This study investigated the possible beneficial effects of reflushing renal grafts with isotonic citrate solution. Rat kidneys were initially flushed with isotonic citrate or with Hartmann's solutions at O C. After 2 hr, half the kidneys of each group were reflushed with isotonic citrate; 22 hr later, all kidneys were transplanted into rats of the same inbred strain. All animals receiving kidneys flushed with Hartmann's solution died, whereas reflushing such kidneys with isotonic citrate significantly ameliorated the deleterious effects of Hartmann's solution. All animals receiving citrate-flushed kidneys survived with relatively good renal function and morphology. However, reflushing itself is not a beneficial procedure and is only of value where an ineffective preserving solution has been used to flush the kidneys initially. There is evidence that some of the adverse effects of flushing develop in the renal medulla.


Speech-in-noise perception in high-functioning individuals with autism or Asperger's syndrome.
High-functioning individuals with autism (HFA) or Asperger's syndrome (AS) commonly report difficulties understanding speech in situations where there is background speech or noise. The objective of this study was threefold: (1) to verify the validity of these reports; (2) to quantify the difficulties experienced; and (3) to propose possible mechanisms to explain the perceptual deficits described. Speech-in-noise perception abilities were measured using speech reception thresholds (SRTs), defined as the speech-to-noise ratio (SNR) at which approximately 50% of the speech is correctly identified. SRTs were measured for 11 individuals with HFA/AS and 9 age/IQ-matched normal-hearing control subjects, using an adaptive procedure, in a non-reverberant sound-attenuating chamber. The speech materials were standardised lists of everyday sentences spoken by a British male speaker. The background sounds were: (1) a single female talker; (2) a steady speech-shaped noise; (3) a speech-shaped noise with temporal dips; (4) a steady speech-shaped noise with regularly spaced spectral dips; and (5) a speech-shaped noise with temporal and spectral dips. SRTs for the HFA/AS group were generally higher (worse) than those for the controls, across the five background sounds. A statistically significant difference in SRTs between the subject groups was found only for those background sounds that contained temporal or spectro-temporal dips. SRTs for the HFA/AS individuals were 2 to 3.5 dB higher than for the controls, equivalent to a substantial decrease in speech recognition. Expressed another way, the HFA/AS individuals required a higher SNR, whenever there were temporal dips in the background sound, to perform at the same level as the controls. The results suggest that the speech-in-noise perception difficulties experienced by individuals with autism may be due, in part, to a reduced ability to integrate information from glimpses present in the temporal dips in the noise.


Helminths collected from imported pet murids, with special reference to concomitant infection of the golden hamsters with three pinworm species of the genus Syphacia (Nematoda: oxyuridae).
A total of 210 individuals of 13 species belonging to 4 subfamilies of Muridae imported into Japan as pets were examined; 5 species of Syphacia (Nematoda: Oxyuridae), Aspiculuris tetraptera (Nematoda: Heteroxynematidae), and Rodentolepis nana (Cestoidea: Hymenolepididae) were collected. Concurrent infection with 3 pinworm species, Syphacia mesocriceti, Syphacia stroma, and Syphacia peromysci, was recorded for the first time in the golden hamster, Mesocricetus auratus. Syphacia mesocriceti was also identified in the desert hamster, Phodopus roborovskii, and S. peromysci was recovered from the fat-tailed gerbil, Pachyuromys duprasi, and the Cairo spiny mouse, Acomys cahirinus. From the pygmy mouse, Mus minutoides, an undetermined species closely resembling Syphacia megaloon and Syphacia ohtaorum, both parasitic in Mus spp., was collected. Females of another undetermined Syphacia sp. were observed in the greater Egyptian gerbil, Gerbillus pyramidum. All of the host-Syphacia associations, except S. mesocriceti in the golden hamsters, were recorded for the first time. It is suggested that overlapping breeding situations provided the opportunity for host switching by the pinworms.


Recent advances in connective tissue disease related interstitial lung disease.
Interstitial lung disease (ILD) is a common manifestation of connective tissue disease (CTD). Although the majority of patients with CTD-ILD are stable or slowly progressive, a significant group exhibits a more severe and progressive decline. Interstitial pneumonia with autoimmune features (IPAF) describes the subset of patients with interstitial pneumonia who have features suggesting underlying autoimmunity, but whose features fall short of a clear diagnosis of CTD. Areas covered: In this focused review, we discuss recent advances in early detection, prognostic evaluation, and management of autoimmune forms of ILD. Expert commentary: Early detection of ILD and a better understanding of factors that impact prognostication may be helpful when making decisions regarding therapeutic interventions. The treatment of CTD-ILD should be comprehensive, is often fraught with challenges and can be complicated by comorbid conditions and extra-thoracic disease activities. Several large randomized studies have examined the impact of immunosuppressive therapy for CTD-ILD, however, additional studies are needed to determine the optimal treatment strategies. Future studies may provide additional information about the best treatments in patients with IPAF.


Autotaxin suppresses cytotoxic T cells via LPAR5 to promote anti-PD-1 resistance in non-small cell lung cancer.
Non-small cell lung cancers that harbor concurrent KRAS and TP53 (KP) mutations are immunologically warm tumors with partial responsiveness to anti-PD-(L)1 blockade; however, most patients observe little or no durable clinical benefit. To identify novel tumor-driven resistance mechanisms, we developed a panel of KP murine lung cancer models with intrinsic resistance to anti-PD-1 and queried differential gene expression between these tumors and anti-PD-1-sensitive tumors. We found that the enzyme autotaxin (ATX), and the metabolite it produces, lysophosphatidic acid (LPA), were significantly upregulated in resistant tumors and that ATX directly modulated antitumor immunity, with its expression negatively correlating with total and effector tumor-infiltrating CD8+ T cells. Pharmacological inhibition of ATX, or the downstream receptor LPAR5, in combination with anti-PD-1 was sufficient to restore the antitumor immune response and efficaciously control lung tumor growth in multiple KP tumor models. Additionally, ATX was significantly correlated with inflammatory gene signatures, including a CD8+ cytolytic score in multiple lung adenocarcinoma patient data sets, suggesting that an activated tumor-immune microenvironment upregulates ATX and thus provides an opportunity for cotargeting to prevent acquired resistance to anti-PD-1 treatment. These data reveal the ATX/LPA axis as an immunosuppressive pathway that diminishes the immune checkpoint blockade response in lung cancer.


Progression of Pre-Existing Vitiligo during Secukinumab Treatment for Psoriasis.
Vitiligo has been considered an unexplained paradoxical phenomenon during biologics use. Herein, we report an adult case of progression of pre-existing vitiligo during secukinumab treatment for psoriasis, and we also examined the immunohistochemical changes in relation to biologics use. He was being administered monthly secukinumab of 300 mg dose for 2 years, and all psoriatic lesions were cleared, but pre-existing hypopigmented lesions became more distinct and larger than before unlike when using adalimumab. A skin biopsy of the hypopigmented lesion showed loss of epidermal melanocytes and absence of gp100 immune activities, and he was finally diagnosed with progression of pre-existing vitiligo. Immunohistochemical staining of vitiligo lesion showed decrease in interleukin-17 and tumor necrosis factor-α and increase in CD8+ T cells, interferon-γ, and CXCL10 after the use of secukinumab. In this study, we suggest that biologics-induced cytokine imbalance play a critical role in vitiligo progression in patients with chronic inflammatory diseases, including psoriasis.


Relationship of medial gastrocnemius relative fascicle excursion and ankle joint power and work performance during gait in typically developing children: A cross-sectional study.
Muscle fascicles lengthen in response to chronic passive stretch through in-series sarcomere addition in order to maintain an optimum sarcomere length. In turn, the muscles' force generating capacity, maximum excursion, and contraction velocity is enhanced. Thus, longer fascicles suggest a greater capacity to develop joint power and work. However, static fascicle length measurements may not be taking sarcomere length differences into account. Thus, we considered relative fascicle excursions through passive ankle dorsiflexion may better correlate with the capacity to generate joint power and work than fascicle length. Therefore, the aim of the present study was to determine if medial gastrocnemius relative fascicle excursions correlate with ankle joint power and work generation during gait in typically developing children. A sample of typically developing children (n = 10) were recruited for this study and data analysis was carried out on 20 legs. Medial gastrocnemius relative fascicle excursion from resting joint angle to maximum dorsiflexion was estimated from trigonometric relations of medial gastrocnemius pennation angle and thickness obtained from B-mode real-time ultrasonography. Furthermore, a three-dimensional motion capture system was used to obtain ankle joint work and power during the stance phase of gait. Significant correlations were found between relative fascicle excursion and peak power absorption (-) r(14) = -0.61, P = .012 accounting for 31% variability, positive work r(18) = 0.56, P = .021 accounting for 31% variability, and late stance positive work r(15) = 0.51, P = .037 accounting for 26% variability. The large unexplained variance may be attributed to mechanics of neighboring structures (e.g., soleus or Achilles tendon mechanics) and proximal joint kinetics which may also contribute to ankle joint power and work performance, and were not taken into account. Further studies are encouraged to provide greater insight on the relationship between relative fascicle excursions and joint function.


Grafting zwitterionic brushes from the surface of an epoxy-based transparent hydrogel for antifouling performance.
Non-specific biofilm formation (biofouling) commonly occurs to the surface of biomedical devices, which causes infection to the human tissues and function loss after implantation. To enhance the antifouling properties on the bioinert hydrogel-based biomaterials, a novel surface grafting approach was developed using surface radical chain-transfer reaction mediated by DL-dithiothreitol (DTT), rather than catalyzed by cytotoxic metal ions. Zwitterionic poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) brushes were grafted on the surface of poly(2-hydroxyethyl methacrylate-co-glycidyl methacrylate) (PHG) to obtain PHG-graft-PMPC (PHG-g-PMPC) hydrogel, which were shown to have tunable surface hydrophilicity while maintaining high water content and transparency. Elemental composition analysis and micromorphology demonstrated the success of surface grafting. Protein adhesion assays were carried out, showing the reduction of bovine serum albumin, lactoferrin, and lysozyme adhesion by ∼90%, 80%, and 70%, respectively, compared to the pristine hydrogels. Significant resistance of bacterial attachment was observed on the surface-modified hydrogels using gram-negativeEscherichia. coliand gram-positiveStaphylococcus aureus, respectively. The PHG-g-PMPC hydrogel is potentially feasible in various biomedical applications, especially for preventing surface biofouling of ophthalmic implants and devices. Furthermore, this de novo approach provides a universal platform for surface functionalization via thiol-epoxy click chemistry and surface radical chain-transfer reaction.


Integration of gastric distension and gustatory responses in the parabrachial nucleus.
Palatable gustatory stimuli promote feeding, whereas gastric distension generally inhibits this behavior. We explored a neural basis for integration of these opposing sensory signals by evaluating the effect of gastric distension on gustatory responses in the parabrachial nucleus (PBN) of anesthetized rats. Sixteen percent of 92 taste cells were coactivated; they responded to independent taste or gastric distension stimulus application. Modulation of taste responses by distension was more prevalent; taste responses declined 37% in response to distension in 25% of the cells and increased by 46% in 10% of cells. Across the whole population, however, the suppressive effect of distension on taste responses was small (6%). The incidence of modulation did not vary as a simple hedonic function of gustatory sensitivity, i.e., similar proportions of sucrose-, citric-acid-, and QHCl-best, but not NaCl-best, neurons were modulated by gastric distension. Coactivated, modulated, and nonmodulated gustatory-responsive cells were intermingled in the gustatory zone of the caudal PBN. The suppression of PBN taste responses by visceral stimulation may reflect a mechanism for satiation and further implicates the PBN in the control of ingestive function.


Inactivation of the Moloney murine leukemia virus long terminal repeat in murine fibroblast cell lines is associated with methylation and dependent on its chromosomal position.
The expression of a retroviral vector with the Moloney murine leukemia virus (Mo-MuLV) long terminal repeat (LTR) promoter after integration into the genome of murine fibroblast cell lines was monitored with the Escherichia coli-derived beta-galactosidase (beta-gal) gene as the reporter. Monoclonal cell lines derived after retroviral infection exhibited a marked heterogeneity in their expression of the reporter gene. We studied two monoclonal cell lines with a single unrearranged copy of the vector provirus integrated into their genome. The first, BB10, expressed the marker enzyme in only 8% of its cell population, whereas in the second, BB16, beta-gal expression could be detected in over 98% of the cells. Treatment of BB10 with the DNA-demethylating agent 5-azacytidine raised the number of beta-gal-positive cells to over 60%. Transfection experiments showed that the Mo-MuLV LTR promoter-enhancer is potentially fully functional in both the BB10 and BB16 cell lines. The inactivated provirus from BB10 cells was cloned and subsequently used to generate retrovirus stocks. The promoter-enhancer activity of its LTR after infection with these BB10-derived viruses showed a variation similar to that of the original virus stocks. Our data showed that (1) inactivation of the Mo-MuLV LTR is a frequent event in murine fibroblast cell lines, (2) inactivation is associated with de novo methylation of cytidine residues, (3) the frequency of inactivation of the provirus must be determined by its chromosomal position, (4) the process of methylation of sequences within the LTR is not necessarily the same as the transcription-repression mechanism that is operating in undifferentiated embryonal carcinoma cells.


Recording violent incidents in the emergency department.
To evaluate the quality of record-keeping by nursing staff after violent incidents in one emergency department in the UK. This study was undertaken between August 2007 and May 2009 in the emergency department of one acute NHS hospital. A retrospective documentary analysis of violent incident forms completed by nursing staff (n = 38), semi-structured interviews (n = 9) and periods of non-participatory, unstructured general observation (52 hours) was conducted. From the documentary analysis, 25 incident forms (n = 38, 66%) were incomplete or lacking detail. Semi-structured interviews with study participants suggested that many violent incidents went unreported. It was widely accepted by the participants that the reporting process did not capture the reality of clinical practice, and the lack of a robust reporting process suggested that incident reporting was seen as a low priority. This study's findings support those of previous studies examining the quality of record-keeping in clinical practice. Poor record-keeping is a common breach of the Nursing and Midwifery Council code of conduct, potentially compromising patient safety. Strategies need to be formulated to improve record-keeping. Avoiding individual blame and consideration of the working environment may encourage staff to complete incident forms.


Shear stress modulates the interaction of platelet-secreted matrix proteins with tumor cells through the integrin alphavbeta3.
Interaction of tumor cells with the vascular wall is required for metastasis from the bloodstream. The precise interaction among metastatic cells, circulating platelets, the vessel wall, and physiological flow conditions remains to be determined. In this study, we investigated the interaction of shear on metastatic cell lines adherent to lipopolysaccharide (LPS)-treated endothelium. Tumor cells were perfused over LPS-treated human umbilical vein endothelial cells (HUVECs) at incremental venous shear rates from 50 to 800 s(-1). At a venous shear rate of 400 s(-1), 3% of adherent tumor cells formed pseudopodia under shear, a process we termed shear-induced activation. Because platelets promote tumor dissemination, we then investigated the effect of pretreating tumor cells with platelet releasate collected from activated platelet concentrate. We found that in the presence of platelet releasate, the number of tumor cells adhering to HUVECs increased and tumor "activation" occurred at a significantly lower shear rate of 50 s(-1). This was inhibited with acetylsalicylic acid. Depletion of fibronectin or vitronectin from the platelet releasate resulted in significantly less adhesion at higher venous shear rates of 600 and 800 s(-1). The integrin alphavbeta3 has been shown to mediate cell adhesion primarily through vitronectin and fibronectin proteins. Inhibition of alphavbeta3, followed by the addition of platelet releasate to the tumor cells, resulted in significantly less adhesion at higher venous shear rates of 600 and 800 s(-1). Collectively, our data suggest that alphavbeta3 promotes the metastatic phenotype of tumor cells through interactions with the secreted platelet proteins vitronectin and fibronectin under venous shear conditions.


Aerosol vaccination with a sendai virus temperature-sensitive mutant (HVJ-pB) derived from persistently infected cells.
Experimental infections of mice with a Sendai virus temperature-sensitive (ts) mutant (HVJ-pB) were studied. Infection with the ts mutant induced the priming effect of interferon production and both humoral and cellular immune responses, although the ts mutant virus neither multiplied satisfactorily in the respiratory tracts of mice nor caused appreciable histopathologic lesions. Inoculation with the ts mutant protected mice from subsequent challenge with a parental wild-type virus. The efficacy of this protection began as little as 1 day after vaccination and continued for at least 12 weeks. It is suggested that serum antibodies were efficacious in the nasal turbinates, while specific immune spleen cells act more protectively in the lungs.


Origin of urinary fibronectin.
Fibronectin (FN) is a major component of the glomerular extracellular matrix and it is also abundant in plasma. In physiologic conditions, FN fragments are excreted into urine. Increased urinary FN excretion has been observed in renal diseases raising the question whether urinary FN could reflect changes in the renal extracellular matrix. This study examines whether urinary FN is filtered from plasma or derived from the kidney and it attempts to specify the potential renal source of urinary FN. (a) To investigate whether urinary FN is filtered from plasma, labeled, biotinylated FN (b-FN) was injected into rats and urine samples were specifically analyzed for b-FN by an immunoblot procedure. (b) To specify the renal source of urinary FN and to evaluate possible alterations of this protein during passage into final urine, tubular fluid was collected from distinct localizations of the nephron by micropuncture techniques. The samples were analyzed for endogenous FN by a highly sensitive immunoblot system, and the pattern was compared with that normally found in final urine. (a) Urine samples collected over a period of 5 days after injection of b-FN contained no labeled FN. Control experiments in rats with highly elevated glomerular permeability confirmed that the plasma levels of injected b-FN were sufficiently high since b-FN was detected in urine in this condition. (b) The FN fragment pattern, with two protein bands at 75 and 45 kilodaltons, that is normally found in final urine, was already present in samples taken from the early proximal tubule and the distal tubule. The fibronectin fragments normally found in urine originate from the kidney and are not derived from plasma. Since these fragments are already observed in early proximal tubular fluid, the glomerulus is the probable source of urinary FN. The FN fragment pattern of early proximal tubular fluid is not substantially altered during passage into final urine, thus reflecting glomerular FN release in urine. It is suggested that examination of urinary FN excretion could be helpful in the assessment of altered glomerular extracellular matrix in pathologic conditions.


Structure of a hexameric form of RadA recombinase from Methanococcus voltae.
Archaeal RadA proteins are close homologues of eukaryal Rad51 and DMC1 proteins and are remote homologues of bacterial RecA proteins. For the repair of double-stranded breaks in DNA, these recombinases promote a pivotal strand-exchange reaction between homologous single-stranded and double-stranded DNA substrates. This DNA-repair function also plays a key role in the resistance of cancer cells to chemotherapy and radiotherapy and in the resistance of bacterial cells to antibiotics. A hexameric form of a truncated Methanococcus voltae RadA protein devoid of its small N-terminal domain has been crystallized. The RadA hexamers further assemble into two-ringed assemblies. Similar assemblies can be observed in the crystals of Pyrococcus furiosus RadA and Homo sapiens DMC1. In all of these two-ringed assemblies the DNA-interacting L1 region of each protomer points inward towards the centre, creating a highly positively charged locus. The electrostatic characteristics of the central channels can be utilized in the design of novel recombinase inhibitors.


HIV risk behavior and access to services: what predicts HIV testing among heterosexually active homeless men?
HIV is a serious epidemic among homeless persons, where rates of infection are estimated to be three times higher than in the general population. HIV testing is an effective tool for reducing HIV transmission and for combating poor HIV/AIDS health outcomes that disproportionately affect homeless persons, however, little is known about the HIV testing behavior of homeless men. This study examined the association between individual (HIV risk) and structural (service access) factors and past year HIV testing. Participants were a representative sample of 305 heterosexually active homeless men interviewed from meal programs in the Skid Row region of Los Angeles. Logistic regression examined the association between past year HIV testing and demographic characteristics, HIV risk behavior, and access to other services in the Skid Row area in the past 30 days. Despite high rates of past year HIV testing, study participants also reported high rates of HIV risk behavior, suggesting there is still significant unmet need for HIV prevention among homeless men. Having recently used medical/dental services in the Skid Row area (OR: 1.91; CI: 1.09, 3.35), and being a military veteran (OR: 2.10; CI: 1.01-4.37) were significantly associated with HIV testing service utilization. HIV testing was not associated with HIV risk behavior, but rather with access to services and veteran status, the latter of which prior research has linked to increased service access. We suggest that programs encouraging general medical service access may be important for disseminating HIV testing services to this high-risk, vulnerable population.


Ethical values in nurse education perceived by students and educators.
Education is considered the first function and mission of the university, and observing educational ethics guarantees the health of the teaching-learning process in the university. The aim of this study was to explore ethical values in nursing education from the perspective of Iranian nursing students and educators. This qualitative study was conducted using the Thematic Content Analyses method. The data were collected from seven semi-structured individual interviews and three focus group discussions from July to November 2015. Participants and research context: The participants were faculty educators of nursing and nursing students in Tehran, capital of Iran, who were selected through purposive sampling. They were recruited gradually. Sampling was continued until data saturation when no new codes were extracted. Ethical committee: This study was conducted after obtaining the approval of Shahid Beheshti University of Medical Sciences Ethics Committee, and informed consent were ensured before conducting the research. The principles of voluntariness, confidentiality, and anonymity were respected during the research process. Seven major themes emerged: human dignity, constructive human relations, educational justice, competency enhancement, excellence view, wisdom, and commitment and accountability. The results of this study indicated that although many of the values, as universal values, were similar to those of other countries-which can be a reflection of the globalization process in the nursing profession and the presence of humanistic and spiritual approaches at the roots of the discipline, some differences could be found in the content of values due to factors such as the people's beliefs, culture, and religion. Iranian nursing students and educators revealed a unique and culture-based set of ethical values.


Increasing burden of urinary tract infections due to intrinsic colistin-resistant bacteria in hospitals in Marseille, France.
The emergence of multidrug-resistant (MDR) Gram-negative bacteria has become a major public health problem, eliciting renewed interest in colistin, an old antibiotic that is now routinely used to treat MDR bacterial infections. Here we investigated whether colistin use has affected the prevalence of infections due to intrinsic colistin-resistant bacteria (CRB) in university hospitals in Marseille (France) over a 5-year period. All data from patients infected by intrinsic CRB were compiled from January 2009 to December 2013. Escherichia coli infections were used for comparison. Colistin consumption data were also collected from pharmacy records from 2008 to 2013. A total of 4847 intrinsic CRB infections, including 3150 Proteus spp., 847 Morganella spp., 704 Serratia spp. and 146 Providencia spp., were collected between 2009 and 2013. During this period, the annual incidence rate of hospital-acquired CRB infections increased from 220 per 1000 patients to 230 per 1000 patients and that of community-acquired CRB infections increased from 100 per 1000 patients to 140 per 1000 patients. In parallel, colistin consumption increased 2.2-fold from 2008 to 2013, mainly because of an increase in the use of colistin aerosol forms (from 50 unitary doses to 2926 unitary doses; P<10(-5)) that was significantly correlated with an increase in the number of patients positive for CRB admitted to ICUs and units of long-term care between 2009 and 2013 (r=0.91; P=0.03). The global rise in infections due to intrinsic CRB is worrying and surveillance is warranted to better characterise this intriguing epidemiological change.


Identification and evaluation of strain B37 of Bacillus subtilis antagonistic to sapstain fungi on poplar wood.
Devaluation of poplar products by sapstain accounts for huge and unpredictable losses each year in China. We had isolated four poplar sapstain fungi, Ceratocystis adiposa Hz91, Lasiodiplodia theobromae YM0737, L. theobromae Fx46, and Fusarium sp. YM05, from five poplar varieties and 13 antagonistic bacteria from nine diverse varieties. After being experimented with agar plates, wood chips, and enzyme activities, strain B37 was identified as the best poplar sapstain biocontrol bacterium. The strain B37 was identified as Bacillus subtilis using sequences of the 16S rRNA gene, physiological biochemical, and morphological characteristics.


Hemorrhagic Stroke in an Adolescent Female with HIV-Associated Thrombotic Thrombocytopenic Purpura.
HIV-1 infection can trigger acute episodes of Idiopathic Thrombocytoponic Purpura (ITP), and Thrombotic Thrombocytopenic Purpura (TTP), particularly in populations with advanced disease and poor adherence to antiretroviral therapy (ART). These diseases should be distinguished because they respond to different treatments. Previous studies done in adults with HIV-TTP have recommended the prompt initiation or re-initiation of ART in parallel with plasma exchange therapy to improve the clinical outcome of these patients. Here, we describe a case of HIV-TTP resulting in an acute hemorrhagic stroke in a 16 year old female with perinatally acquired HIV infection and non-adherence to ART, who presented with severe thrombocytopenia, microangiopathic hemolytic anemia, and a past medical history of HIV-ITP. Both differential diagnosis and treatments for HIV-ITP and HIV-TTP were considered simultaneously. A decrease in plasma ADAMTS13 activity (<5%) without detectable inhibitory antibodies confirmed the diagnosis of HIV-TTP. Re-initiation of ART and plasma exchange resulted in a marked decrease in the HIV-RNA viral load, recovery of the platelet count, and complete recovery was achieved with sustained virologic suppression.


Outcome of induced labor in 931 term pregnancies.
An analysis of 931 consecutive inductions of labor over an eight-year period is presented. The success rate was 90.4%. Spontaneous vaginal delivery was achieved in 83.5% of cases and the induction-delivery interval was less than 12 hours in 82.6% of cases. The preinduction state of the cervix most significantly influenced the outcome of labor, followed by maternal age and parity. Provided induction of labor was by synchronous use of forewater amniotomy and oxytocin titration, labor outcome was regularly predictable two hours after induction using the concept of latent period of labor and the cervical dilatation at eight hours from the induction. When the latent period was two hours or less, 64.2% of the patients delivered within eight hours, and vaginal delivery was achieved in all women in whom the cervical dilatation was 8 cm or more at eight hours from the induction of labor. The maternal complication rate was 12.1%, the early neonatal morbidity was 11.6%, and the stillbirth rate was 2.3%.


Stereotactic radiosurgery and stereotactic fractionated radiotherapy for metastatic tumors of the spine.
The objectives of this paper are to describe pain control, neurologic improvement, local tumor control, progression-free survival, and overall survival of spine SRS/SFRT patients, and to compare our outcomes with other studies on spine stereotactic radiotherapy for metastatic tumors. A chart review of patients who underwent spine SRS/SFRT was done. Information was collected on patient age, sex, histology, site treated, pain relief, local control, neurologic function, prescription dose, and complications. Descriptive statistics, median local control rates, progression-free survival, and overall survival were calculated. Twenty eight SRS and 3 SFRT target volumes in 21 patients were studied. Eighteen underwent SRS and 3 underwent SFRT for metastasis from August 2012 to February 2016. Follow-up ranged from 4 to 41 months. Average dose was 16.6 ± 3.9 Gy. Spine SRS mean target volume was 31.1 cc (95% CI, 21.7-40.6 cc). Median overall survival after treatment was 16 months (95% CI, 9.7-22.3 months) and median progression-free survival was 13 months (95% CI, 8.4-17.6 months). Local control was 46%, 30%, and 15% at 6, 8, and 10 months, respectively. Average onset of pain relief is 4.9 days (95% CI, 0.8-8.9 days). One patient (5%) developed post SRS vertebral compression fracture. SRS/SFRT is a safe and effective alternative to EBRT for the treatment of spine metastasis. Improvement in pain control and motor strength and incidence of adverse events are comparable with other studies. Local tumor control was lower in our series due to a lower mean prescribed dose.


Disruption of MEF2 activity in cardiomyoblasts inhibits cardiomyogenesis.
Myocyte enhancer factors (MEF2s) bind to muscle-specific promoters and activate transcription. Drosophila Mef2 is essential for Drosophila heart development, however, neither MEF2C nor MEF2B are essential for the early stages of murine cardiomyogenesis. Although Mef2c-null mice were defective in the later stages of heart morphogenesis, differentiation of cardiomyocytes still occurred. Since there are four isoforms of MEF2 factors (MEF2A, MEF2B, MEF2C and MEF2D), the ability of cells to differentiate may have been confounded by genetic redundancy. To eliminate this variable, the effect of a dominant-negative MEF2 mutant (MEF2C/EnR) during cardiomyogenesis was examined in transgenic mice and P19 cells. Targeting the expression of MEF2C/EnR to cardiomyoblasts using an Nkx2-5 enhancer in the P19 system resulted in the loss of both cardiomyocyte development and the expression of GATA4, BMP4, Nkx2-5 and MEF2C. In transiently transgenic mice, MEF2C/EnR expression resulted in embryos that lacked heart structures and exhibited defective differentiation. Our results show that MEF2C, or genes containing MEF2 DNA-binding sites, is required for the efficient differentiation of cardiomyoblasts into cardiomyocytes, suggesting conservation in the role of MEF2 from Drosophila to mammals.


Psoriatic arthritis.
To evaluate the clinical pattern of psoriatic arthritis in patients attending a tertiary referral centre in South India. Case records of one hundred and sixteen patients with psoriatic arthritis (PsA) who had attended our Rheumatology Department were analysed using demographic, clinical, laboratory and radiographic variables and the data were compared with other studies. Among 116 patients, 78 were males and 38 were females (ratio 2:1). Peak incidence (69%) was in the fourth and fifth decades. One patient had juvenile psoriatic arthritis (onset <16 years of age). Symmetric polyarthritis (48.3%) was the commonest subtype. Arthritis followed the skin lesions in 50.8% of patients, preceded in 12.1% and occurred simultaneously in 37.1%. Knee (66.4%) was the commonest joint involved. Extra-articular features like sausage digits (19%), enthesitis (7.8%) and eye manifestations (1.7%) like conjunctivitis and uveitis were observed. Psoriasis vulgaris (81%) was the commonest psoriatic lesion. Scalp (57.8%) was the most common hidden site. All the three patients with DIP arthritis alone had nail lesions. ESR and C-reactive protein were elevated in 51.7% and 43.9% of patients respectively. Rheumatoid factor was positive in 3.4 % and antinuclear antibody (ANA) was present in 5.4% (3/56) of patients. HIV infection was detected in 2.3% (1/44) of patients. Radiographic features like sacroiliitis (11.2%), calcaneal spur (7.8%), erosions (5.2%) and syndesmophytes (5.2%) were observed. One patient had 'pencil-in-cup deformity'. Psoriatic arthritis is more common in males. Symmetric polyarthritis is the commonest subtype. Arthritis commonly follows the skin lesions. Psoriasis vulgaris is the most common skin lesion and scalp is the commonest hidden site. ESR and CRP can be normal in psoriatic arthritis.


Painful erythematous, infiltrated papulonodules in a middle aged man.
Cutaneous leiomyomas (CL) often present as painful tumors in the skin. Herein we report an adult man who presented with multiple, erythematous papulonodules in both segmental and non-segmental distribution.


A case of dilated cardiomyopathy manifested by exercise-induced left bundle branch block.
We report an extremely rare case of dilated cardiomyopathy manifested by exercise-induced left bundle branch block. A 63-year-old female came to our hospital because supraventricular arrhythmia had been detected at a check-up. A treadmill exercise test induced left bundle branch block. However, chest X-ray and echocardiography revealed no abnormal finding. Two years later, the patient experienced exertional dyspnea. A chest X-ray examination showed cardiomegaly, and echocardiography showed a moderate impairment of left ventricular function with left ventricular dilatation. The diagnosis of dilated cardiomyopathy was made by left ventricular myocardial biopsy. No previous cases have initially shown exercise-induced left bundle branch block which was followed by left ventricular dysfunction due to dilated cardiomyopathy. Careful long-term observation of the clinical course is necessary in patients with exercise-induced left bundle branch block which shows no significant underlying disease.


Why should we screen for male fertility?
An increasing number of studies show declining sperm counts; however, semen analyses are uncommon until the evaluation for infertility. Semen analysis is a safe, reliable and relatively inexpensive screening test, assessing male fertility and directing further work-up. In young men, the use of semen analysis may identify disease prior to attempted conception and result in improved fertility potential when combined with lifestyle changes, medical or surgical therapy. Furthermore, if sperm counts are significantly low, evaluation and management for genetic causes can be initiated. Our commentary outlines why screening for male infertility in young adult men may be beneficial. We discuss options for early intervention, including sperm cryopreservation, if defects in sperm parameters are identified.


The Analysis of Two BDNF Polymorphisms G196A/C270T in Chinese Sporadic Amyotrophic Lateral Sclerosis.
Amyotrophic lateral sclerosis (ALS) is an ethnically heterogeneous motor neuron disease that results from the selective death of motor neurons in the brain and spinal cord. Brain-derived neurotrophic factor (BDNF) is widely distributed across the central and peripheral nervous systems and plays neurotrophic and other physiological roles in various brain regions. Alterations of neurotrophin availability have been proposed as a pathogenic mechanism underlying ALS neurodegeneration. Several genetic studies have shown a significant association between schizophrenia, Alzheimer's disease, and Parkinson's disease and certain BDNF polymorphisms, specifically G196A (rs6265) and C270T (rs56164415). However, the relationship between the G196A and C270T polymorphisms and ALS has never been investigated. We hypothesized that sporadic ALS (sALS) and disease susceptibility could arise due to BDNF polymorphisms and investigated the relationship between ALS and the BDNF polymorphisms G196A and C270T in a large Chinese cohort. We demonstrate that the frequency of the CT genotype and of the C270T T allele was significantly higher in the ALS group than in controls, although G196A was not associated with sALS. These data provide the first demonstration that the BDNF C270T polymorphism may be a candidate susceptibility locus for sALS, at least in Han Chinese.


Gated photon correlation spectroscopy for acoustical particle velocity measurements in free-field conditions.
The measurement of acoustic pressure at a point in space using optical methods has been the subject of extensive research in airborne acoustics over the last four decades. The main driver is to reliably establish the acoustic pascal, thus allowing the calibration of microphones with standard and non-standard dimensions to be realized in an absolute and direct manner. However, the research work so far has mostly been limited to standing wave tubes. This Letter reports on the development of an optical system capable of measuring acoustic particle velocities in free-field conditions; agreement within less than 0.6 dB was obtained with standard microphone measurements during these initial experiments.


Treated wastewater effluent as a source of pyrethroids and fipronil at todos santos bay, Mexico: Its impact on sediments and organisms.
Pyrethroids are insecticides widely used to control pests and disease vectors in residential areas and agricultural lands. Pyrethroids are emerging pollutants, and their use is a growing concern because of their toxicity potential to aquatic organisms. Todos Santos Bay and the Punta Banda estuary, 2 coastal bodies located to the south of the Southern California Bight, were studied to establish a baseline of the current conditions of pollution by pyrethroids and fipronil. Eight pyrethroids, along with fipronil and its 2 metabolites, were determined in effluents from wastewater-treatment plants (n = 3), surface sediments (n = 32), and 3 locations with mussels (Mytilus californianus, n = 9). Bifenthrin, permethrin, and cypermethrin were the most common pyrethroids found in the study areas and were widespread in sediments, mussels, and wastewater-treated effluents. Fipronil and its metabolites were detected in mussels and wastewater-treated effluents only. Total pyrethroid concentrations in sediments ranged from 0.04 to 1.95 ng/g dry weight in the Punta Banda estuary (n = 13) and from 0.07 to 6.62 ng/g dry weight in Todos Santos Bay (n = 19). Moreover, total pyrethroids in mussels ranged from 1.19 to 6.15 ng/g wet weight. Based on the toxic unit data calculated for pyrethroids and fipronil for Eohaustorius estuarius and Hyalella azteca, little to no impact is expected to the benthic population structure. Environ Toxicol Chem 2017;36:3057-3064. © 2017 SETAC.


Monoclonal antibodies specific for porcine monocytes/macrophages: macrophage heterogeneity in the pig evidenced by the expression of surface antigens.
Macrophages are widely distributed in most tissues of the body, where they play important roles in host defense and repair of tissue damage. In this report we describe the production and characterization of a panel of six monoclonal antibodies (mAb) against porcine macrophages and their use for phenotyping tissue macrophages. All mAbs were produced by immunizing mice with porcine alveolar macrophages. Three of them (2A10/11, 3B11/11 and 3F7/11) react mainly with macrophages and, at a lower extent, blood monocytes, whereas the others (1E12/11, 2C12/10 and 4E9/11) also recognize granulocytes. Antigens recognized by these antibodies could be characterized by Western blot and/or immunoprecipitation, with the exception of that one recognized by 2C12/10. By their behavior in SDS-PAGE under reducing and nonreducing conditions, all seem to be single polypeptides, whose apparent molecular weight under reducing conditions are: 1E12/11 and 3B11/11 larger than 204 kDa; 2A10/11, 150 kDa; 4E9/11, 125-170 kDa; and 3F7/11, 135 kDa. Immunohistochemical analyses of both lymphoid and non-lymphoid organs using these mAbs reveal important antigenic heterogeneity among tissue macrophages. These mAbs are, therefore, useful tools for the study of porcine macrophage maturation and differentiation and for determining their heterogeneity both in normal and pathological conditions.


Randomized, Controlled Trial of an Intervention Combining Self-Care and Self-Hypnosis on Fatigue, Sleep, and Emotional Distress in Posttreatment Cancer Patients: 1-Year Follow-Up.
Cancer can provoke fatigue, sleep disturbances, and emotional distress. Hypnosis interventions have shown positive short-term effects on these symptoms. However, less is known about their long-term effects. This study assessed the short- and long-term effects of a group intervention combining self-care and self-hypnosis on these symptoms in posttreatment cancer patients. Ninety-five female cancer survivors were randomized to either a hypnosis group intervention or wait-list control. Results showed significant decreases in fatigue, sleep difficulties and emotional distress after intervention for the hypnosis group intervention in comparison to the wait-list control. Most of these positive effects were maintained at 1-year follow-up. Most participants received the hypnosis group intervention approximately 10.65 months after diagnosis, and it is possible that delivering the intervention earlier after diagnosis could have achieved a more robust impact. Further studies are needed to replicate these results in comparison to an active control condition and investigate the best time postdiagnosis for initiating the intervention.


Positive relationship between the dosage of pindolol and its antihypertensive effect.
Pindolol was given once a day to 15 patients with mild to moderate hypertension to investigate whether once-daily dosage controls blood pressure for 24 h and whether a paradoxical rise in blood pressure occurs with increasing dosage. Placebo and pindolol, 10, 20, and 30 mg, were administered in double-blind or single-blind fashion. Blood pressure and heart rate were determined under identical and strictly standardized conditions 24-26 h after giving the last capsule. Blood pressure levels were significantly lower during all periods of active treatment compared with placebo levels. There was a clear relation between dosage of pindolol and its antihypertensive effect. These results demonstrate the pindolol can be given once daily in the treatment of hypertension and that a paradoxical rise of blood pressure does not occur with dosages up to 30 mg pindolol daily.


Virus-Specific Cellular Response in Hepatitis C Virus Infection.
Studies performed on chimpanzees and humans have revealed that strong, multispecific and sustained CD4(+) and CD8(+) T cell immune responses is a major determinant of hepatitis C virus (HCV) clearance. However, spontaneous elimination of the virus occurs in minority of infected individuals and cellular response directed against HCV antigens is not persistent in individuals with chronic infection. This review presents characteristics of the HCV-specific T cell response in patients with different clinical course of infection, including acute and chronic infection, persons who spontaneously eliminated HCV and non-infected subjects exposed to HCV. Detection of HCV-specific response, especially in non-infected subjects exposed to HCV, may be indicative of HCV prevalence in population and rate of spontaneous viral clearance. Understanding the mechanisms and role of HCV-specific cellular immune response would contribute to better understanding of HCV epidemiology, immunopathogenesis and may help to design an effective vaccine.


Cytotaxonomy of the Simulium damnosum complex and description of new cytotypes in the Tukuyu focus, southwest Tanzania.
Larvae of Simulium damnosum complex collected from rivers draining Tukuyu onchocerciasis focus were chromosomally examined. Of the 970 larvae analysed, 910 were identified as Kiwira form, a newly described cytotype found in all S. damnosum larval habitats in the Tukuyu area, while 51 were classified as a new subpopulation, tentatively named as Kasyabone form. The F1 larval progeny obtained from wild caught human biting S. damnosum and reared in the laboratory were chromosomally examined. 509 F1 larvae from 70 females blood fed on human volunteers were identified as Kiwira form. As the main human-biting member of the complex in the Tukuyu area, and because some of the wild caught females had developing filarial larvae indistinguishable from those of Onchocerca volvulus, Kiwira form is thus incriminated as the local vector of onchocerciasis. These observations are discussed with respect to previous literature.


Inducible Sequential Oxidation Process in Water-Soluble Copper Nanoclusters for Direct Colorimetric Assay of Hydrogen Peroxide in a Wide Dynamic and Sampling Range.
Direct and fast detection methods for H2O2 have great demand in materials science, biology, and medicine. Colorimetric assay of H2O2 has been regarded as one versatile approach that can avoid tedious operation and complicated setup. In this report, we provided a cost-effective and time-saving H2O2 colorimetric assay strategy based on a mercaptosuccinic acid (MSA)-stabilized Cu nanocluster (NC) probe without using any chromogenic reagent. Direct and fast colorimetric detection of H2O2 was realized based on the color change of MSA-capped Cu NCs in aqueous medium. It was found that the Cu NCs presented eligible resistance to natural oxidation either in concentrated solution or in the powder state. However, the dissolved oxygen in a highly diluted solution of the Cu NCs could trigger the aggregation of the Cu NCs and their further fusion into small Cu nanoparticles (NPs). When this diluted solution served as a probe solution for detecting H2O2, a sequential oxidation process occurred in the newly formed Cu NPs, including the cleavage of MSAs on the surface and conversion of Cu into Cu2O, leading to the probe with capacity for H2O2 assay in a wide dynamic and sampling range. The sensitive solution color change was attributed to the growth of the Cu NPs (fading of plasmonic absorption) upon the addition of low levels of H2O2 and the transition of the valence states of Cu (color reactions) upon the addition of high levels of H2O2. A concentration range of H2O2 from 1 μM to 1 M could be detected by a small dose of the probe. Moreover, the Cu NCs powder subsequent to storage for 10 months could maintain a similar sensitivity for H2O2 assay, which provides possibilities for a wide range of practical applications in water samples.


Teacher asthma management and information seeking scale.
This article presents the design and evaluation of the Teacher Asthma Management and Information Seeking Scale. Based on a sample of 593 kindergarten to eighth grade teachers, the scale yielded two factors: the Asthma Management (= 0.90) and the Information Seeking Factor (= 0.71). This scale fills a needed gap in the literature regarding assessment tools for school-based asthma management that focus on teacher behavior.


Responsiveness of clinical and laboratory measures to intervention effects in children with developmental coordination disorder.
To compare responsiveness of the Movement Assessment Battery for Children-2 (MABC-2) and segment kinematics and center of pressure measures in detecting intervention effects in children with developmental coordination disorder. Motion Analysis Laboratory (MAL) data from 21 children with developmental coordination disorder (mean age 11.0 years) in a randomized control trial were analyzed using effect size, minimal detectable difference, and parent and child report of meaningfulness (χ2 tests). The MABC-2 and MAL data showed moderate-large effect sizes (0.7-1.8). The MABC-2 detected large portions of children whose change exceeded the minimal detectable difference (47.6%-71.4%); MAL data detected small portions (0%-19.0%). Neither tool correlated well with meaningfulness (χ2 = 0.186-5.724; P > .10). Both tools detected change in the overall group; however, only the MABC-2 detected individual change exceeding potential measurement error. Although both assessment tools are responsive, they may be responsive to different types of change. Therefore, assessment constructs should be matched to intervention goals.


Vaccinia scars associated with improved survival among adults in rural Guinea-Bissau.
In urban Guinea-Bissau, adults with a vaccinia scar had better survival but also a higher prevalence of HIV-2 infection. We therefore investigated the association between vaccinia scar and survival and HIV infection in a rural area of Guinea-Bissau. In connection with a study of HIV in rural Guinea-Bissau, we assessed vaccinia and BCG scars in 193 HIV-1 or HIV-2 infected and 174 uninfected participants. Mortality was assessed after 2(1/2)-3 years of follow-up. The analyses were adjusted for age, sex, village, and HIV status. The prevalence of vaccinia scar was associated with age, village, and HIV-2 status but not with sex and schooling. Compared with individuals without any scar, individuals with a vaccinia scar had better survival (mortality rate ratio (MR) = 0.22 (95% CI 0.08-0.61)), the MR being 0.19 (95% CI 0.06-0.57) for women and 0.40 (95% CI 0.04-3.74) for men. Estimates were similar for HIV-2 infected and HIV-1 and HIV-2 uninfected individuals. The HIV-2 prevalence was higher among individuals with a vaccinia scar compared to individuals without a vaccinia scar (RR = 1.57 (95% CI 1.02-2.36)). The present study supports the hypothesis that vaccinia vaccination may have a non-specific beneficial effect on adult survival.


Bereavement in Pakistan during the COVID-19 pandemic: Psychometric analysis of the Pandemic Grief Scale-Urdu Version (PGS-UV).
With nearly 4 million deaths worldwide, COVID-19 has resulted in a great loss of life. For many of the bereaved, the grieving process has been especially difficult due to COVID-19 spatial distancing procedures and the traumatic circumstances of this particular form of loss. Consequently, a large number of the world's bereaved are experiencing dysfunctional levels of grief. To assess such grief, the Pandemic Grief Scale (PGS) was created to identify those affected who may benefit from professional support. This study aimed to psychometrically analyze the properties of the Urdu version of the scale, among a sample of 272 Pakistanis who lost a loved one to COVID-19 from March to June 2021. Results revealed that the scale was found to be a reliable and valid tool for assessing dysfunctional pandemic grief for both men and women. However, unique gender differences were found. Additional research should further confirm the psychometric properties of the PGS on other culturally diverse samples.


Endoparasites of horses from the Formiga city, located in center-west region of the state of Minas Gerais, Brazil.
With the aim of studying the endoparasite fauna of horses from the Formiga city, located in center-west region of the state of Minas Gerais, 25 animals that were naturally infected with helminths were evaluated. By means of parasitological necropsies, different endoparasites were found. The subfamily Cyathostominae presented the highest incidence, followed by Trichostrongylus axei, Oxyuris equi, Triodontophorus serratus, Strongyloides westeri, Strongylus edentatus, Habronema muscae, Parascaris equorum, Probstmayria vivipara, Strongylus vulgaris, Gasterophilus nasalis, Anoplocephala magna and Anoplocephala perfoliata. In the present study, if the species Probstmayria vivipara was not considered in the prevalence, the frequency of Cyathostominae was equivalent to 94.85%. The results obtained in this study allowed us to detect and identify different species of helminths in horses, and confirmed the high incidence of nematodes belonging to the subfamily Cyathostominae in the center-west region of Minas Gerais.


Incorporation of biaryl units into the 5' and 3' ends of sense and antisense strands of siRNA duplexes improves strand selectivity and nuclease resistance.
Small interfering RNA (siRNA) is a noncoding RNA with considerable potential as a new therapeutic drug for intractable diseases. siRNAs can be rationally designed and synthesized if the sequences of the disease-causing genes are known. In this paper, we describe the synthesis and properties of siRNAs modified with biaryl units. We found that incorporation of biaryl units into the 5' and 3' ends of sense and antisense strands of siRNA duplexes improved strand selectivity and nuclease resistance.


Using a chat-based informed consent tool in large-scale genomic research.
We implemented a chatbot consent tool to shift the time burden from study staff in support of a national genomics research study. We created an Institutional Review Board-approved script for automated chat-based consent. We compared data from prospective participants who used the tool or had traditional consent conversations with study staff. Chat-based consent, completed on a user's schedule, was shorter than the traditional conversation. This did not lead to a significant change in affirmative consents. Within affirmative consents and declines, more prospective participants completed the chat-based process. A quiz to assess chat-based consent user understanding had a high pass rate with no reported negative experiences. Our report shows that a structured script can convey important information while realizing the benefits of automation and burden shifting. Analysis suggests that it may be advantageous to use chatbots to scale this rate-limiting step in large research projects.


T lymphocytes and mast cells express messenger RNA for interleukin-4 in the nasal mucosa in allergen-induced rhinitis.
We have investigated the phenotype of interleukin-4 (IL-4) mRNA+ cells in the nasal mucosa of six subjects with allergic rhinitis before and 24 hr after local allergen provocation with grass pollen extract. Serial cryostat sections were cut from paraformaldehyde-fixed snap-frozen nasal biopsies, and immunocytochemistry (APAAP) followed by in situ hybridization performed on the same sections. For immunocytochemistry, antibodies against CD3, tryptase, major basic protein (MBP) and CD68 were used to identify T cells, mast cells, eosinophils and macrophages, respectively. Hybridization studies were performed using a digoxigenin-labelled IL-4 riboprobe. Nitroblue tetrazolium (NBT) and X-phosphate-5-bromo-4-chloro-3-indoly phosphate (BCIP) served as chromogens to detect hybridization IL-4 mRNA signals. Significant increases in T lymphocytes and eosinophils and in the number of IL-4 mRNA+ cells were observed after allergen challenge. Double immunocytochemistry/in situ hybridization demonstrated that the majority of IL-4 mRNA+ cells after allergen challenge were CD3+ (73.7% +/- 1.6). Lower numbers of IL-4 mRNA hybridization signals were co-localized to tryptase+ cells (26.0% +/- 1.6). In contrast, no IL-4 mRNA hybridization signals were co-localized to either eosinophils or macrophages. These results indicate that after allergen challenge T cells are the principal cellular source of IL-4 mRNA transcripts during human late nasal responses, with a lesser contribution from mast cells.


[Omental Flap for the Device Infection of the HeartMate II].
Case 1:An 18-year-old male underwent emergent left extracorporeal ventricular assist device(eVAD) implantation for a cardiogenic shock because of dilated cardiomyopathy (DCM). After listing for heart transplant, he underwent a HeartMate II implantation as bridge-to-bridge(BTB) therapy. The omental flap was simultaneously used to prevent device infection that could have been induced by the infected malgranulation around the cannulas of the eVAD. Eventually, he was discharged and waiting for transplantation. Case 2:A 30-year-old male with DCM underwent emergent eVAD implantation for left ventricular support, centrifugal veno-pulmonary artery extracorporeal membrane oxygenation (ECMO) for right ventricular and respiratory support, and mitral valve replacement. After weaning of ECMO, he was listed for a heart transplant and underwent a HeartMate II implantation as BTB therapy. However, liver dysfunction and malnutrition prolonged wound healing. Despite applying vacuum assist closure device to promote wound healing, part of the driveline and pump housing were exposed. Therefore, radical debridement and omentopexy were performed for infection control. He was discharged after complete wound healing.


Arrhythmias in Repaired Tetralogy of Fallot: A Scientific Statement From the American Heart Association.
Arrhythmia and sudden cardiac death remain common in repaired tetralogy of Fallot and affect even those with excellent anatomic repairs. Atrial arrhythmia often has mechanisms different from those in acquired heart disease. Ventricular arrhythmia remains a major source of mortality in repaired tetralogy of Fallot. Noninvasive risk stratification is important to identify patients who may benefit from ablation or primary prevention implantable cardioverter defibrillators. Multiple noninvasive risk factors are associated with ventricular arrhythmia, but no universally accepted risk stratification algorithm exists. The mechanism of ventricular arrhythmia is usually attributable to a consistent and discrete set of slowly conducting anatomic isthmuses related to both the native anatomy and the consequences of the surgical repair, which interact with ventricular remodeling to provide arrhythmic substrate. This substrate can be identified during electroanatomic mapping and prophylactically ablated in appropriate patients. This scientific statement discusses the mechanisms and treatment of arrhythmia in repaired tetralogy of Fallot.


Frontal Sinus Cholesteatoma Presenting with Intracranial and Orbital Complications: Diagnosis and Treatment.
Frontal sinus keratoma or cholesteatoma is a rare disease of paranasal sinuses and presents as a slow-growing mass that becomes symptomatic as it grows to the surrounding structures. Intracranial complications are not a common presentation and are potentially life-threatening. Frequently the final diagnosis is only made intraoperatively because several other frontal sinus tumors behave likewise. Definitive treatment requires complete removal of the keratoma, and a combined endoscopic and external frontal sinus approach is a good treatment option. In this report, we presented a 68-year-old female with frontal sinus cholesteatoma with diagnostic and therapeutic features of this pathology with the review of the literature.


The spectrum of worry in the community-dwelling elderly.
In this study, we examine the prevalence and distribution of worry, its content, and its associations with quality of life and depression, based on a large sample of community-dwelling elderly. We will attempt to distinguish between pathological and non-pathological worry based on these associations. Community survey. Inner-city population. A total of 2136 people aged between 65 and 96, of whom 66% were women, were recruited through general practitioners and interviewed in their own homes. The GMS-AGECAT structured psychiatric interview was used to rate symptoms which were classified into five levels of severity of worry ranging from simple, non-excessive to generalised anxiety disorder (GAD). In this study, 79% of the participants reported worrying, 37% worrying excessively, while 20% reported excessive, uncontrollable worry and 6.3% met criteria for GAD. Prevalence of all types of worry declined with age and was lower in men. The prevalence of depressed mood was similar in those without worry and those with non-severe worry (Wald post hoc test, p = 0.06) but rose significantly with each level of severe worry (Wald post hoc tests, all p < 0.05). Major depressive disorder was absent in those who did not worry, and had a prevalence of only 0.2% in those with non-severe worry (p = 0.552, Fisher's exact test). It has a significantly elevated prevalence at all levels of excessive worry, and a significantly higher prevalence in those with GAD. All levels of excessive worry were associated with reduced quality of life. Severe worry is highly prevalent in the elderly; most severe worriers do not meet criteria for GAD, but have a reduced quality of life and an increased prevalence of depression.


Dopamine autoreceptor agonists as potential antipsychotics. 3.6-Propyl-4,5,5a,6,7,8-hexahydrothiazolo[4,5-f]quinolin-2-amine.
A series of rigid tricyclic analogues of the dopamine (DA) agonist PD 118440 [4-(1,2,5,6-tetrahydro-1-propyl-3-pyridinyl)-2-thiazolamine] was synthesized and evaluated for dopaminergic activity and DA autoreceptor selectivity. (R)-(+)-6-Propyl-4,5,5a,6,7,8-hexahydrothiazolo[4,5-f]quinolin+ ++-2-amine [+)-6) was identified as the most selective DA autoreceptor agonist from this group of compounds. It inhibited spontaneous locomotor activity (LMA) in rodents, reversed the gamma-butyrolactone (GBL) induced accumulation of rat striatal DOPA and inhibited brain DA neuronal firing, all suggestive of direct DA autoreceptor agonist activity. However, (+)-6 is not completely free of postsynaptic DA activity, as evidenced by its stimulation of LMA in rats at high doses and its ability to produce stereotypy. On the other hand, (-)-6 appears to be a weak partial DA agonist with some effects on brain DA synthesis only at high doses. Like other DA autoreceptor agonists and DA antagonists, (+)-6 inhibited Sidman conditioned avoidance in squirrel monkeys, a test predictive of clinical antipsychotic activity. However, unlike classical antipsychotics, (+)-6 did not induce dystonias in haloperidol-sensitized squirrel monkeys, suggesting a minimal propensity toward extrapyramidal side effects (EPS).


Subtype maturation of spiral ganglion neurons.
We review recent progress in the characterization of spiral ganglion neurons (SGNs), the afferent neurons that transmit sound information from mechanosensory hair cells in the inner ear to the central nervous system. Single-cell ribonucleic acid sequencing studies of murine SGNs have demonstrated that SGNs consist of molecularly distinct subtypes. The molecularly defined SGN subtypes likely correspond to SGN subtypes previously identified on the basis of physiological properties, although this has not been experimentally demonstrated. Subtype maturation is completed postnatally in an activity-dependent manner and is impaired in several models of hearing loss. The recent molecular studies open new avenues to rigorously test whether SGN subtypes are important for the encoding of different sound features and if they show differential vulnerability to genetic factors and environmental insults. This could have important implications for the development of therapeutic strategies to treat hearing loss.


Optimal time interval between myeloablative whole body irradiation and reconstitution with syngeneic bone marrow graft.
The optimal time interval between termination of radiation therapy and marrow grafting has been studied in an animal model of syngeneic bone marrow transplantation, using a limiting number of bone marrow cells. Optimal survival was achieved when reconstitution took place 24 h following termination of radiation therapy at all cell doses studied, including 5 x 10(4), 2 x 10(5) and 1 x 10(6) cells/recipient. The worst results were observed when bone marrow cells were infused immediately after irradiation. These results suggest that reconstitution of lethally irradiated recipients requires migration of irradiated host marrow cells and establishment of adequate 'bone marrow space', which is optimal at 24 h following termination of whole body irradiation.


Creation of an antiferromagnetic exchange spring.
We present evidence for the creation of an exchange spring in an antiferromagnet due to exchange coupling to a ferromagnet. X-ray magnetic linear dichroism spectroscopy on single crystal Co/NiO(001) shows that a partial domain wall is wound up at the surface of the antiferromagnet when the adjacent ferromagnet is rotated by a magnetic field. We determine the interface exchange stiffness and the antiferromagnetic domain wall energy from the field dependence of the direction of the antiferromagnetic axis, the antiferromagnetic pendant to a ferromagnetic hysteresis loop. The existence of a planar antiferromagnetic domain wall, proven by our measurement, is a key assumption of most exchange bias models.


Adynamic cardiomyoplasty: effect on cardiac efficiency and contractile reserve in dogs with adriamycin-induced cardiomyopathy.
The girdling effect of the skeletal muscle wrap seems to be the primary mechanism of action of cardiomyoplasty. It is associated with a myocardial sparing effect. Myocardial sparing effect has been shown with an active muscle wrap or an active muscle wrap acutely turned "OFF". The purpose of the study was to evaluate the effect of a passive skeletal muscle wrap on cardiac energetics parameters and contractile reserve in a canine model of cardiomyopathy. Six dogs with adriamycin-induced cardiomyopathy were studied. Three dogs underwent right latissimus dorsi adynamic cardiomyoplasty and 3 served as controls. Cardiac and coronary sinus catheterizations were performed at 0 and 6 weeks. A dobutamine stress test was performed at 6 weeks. Myocardial oxygen consumption was not reduced in the cardiomyoplasty group (139.20+/-86.90 Joules/min) compared to the control group (95.10+/-12.60 Joules/min, P = 0.27) at 6 weeks. Mechanical cardiac efficiency was increased in the cardiomyoplasty group (33.15+/-4.40%) compared to the control group (24.50+/-2.70%, P = 0.049) at 6 weeks. Left ventricular end diastolic diameter index was reduced in the cardiomyoplasty group (38.00+/-1.70 mm/m2) compared to the control group (46.30+/-1.55 mm/m2, P = 0.049) at 6 weeks. Indices of diastolic function -dp/dt, and tau were not significantly affected by adynamic cardiomyoplasty. Max dp/dt was increasing more in the cardiomyoplasty group than in the control group (P = 0.07) during dobutamine stress test. Mechanical cardiac efficiency was better preserved by the adynamic cardiomyoplasty. Myocardial contractile reserve might be better preserved with cardiomyoplasty.


[The effect of hyperglycemia on indices of biochemical blood analysis in vitro.]
The purpose of study was to detect possible deviations between the results of biochemical analysis of blood and true values in conditions of hyperglycemia in vitro and dependences of the given alterations from group belonging of analyzed blood. The biochemical analysis was applied to blood samples of patients with various blood groups according system AB0 in conditions of normo- and hyperglycemia in vitro. The criterion for choice was established the content of main biochemical indices of blood (total protein, total bilirubin, glucose, total cholesterol, urea, creatinine, activity of hylaninamitotransferase (ALT), aspartataminotransferase (AST), lactatedehydrogenase (LDG)) within the reference limits. The hyperglycemia was developed in vitro using 5% glucose solution and corresponded to 20,49±0,05 and 46,37±0,63 mmol/l. The content of total protein and total cholesterol turned out to be the most stable indices. The effect of increased level of glucose to following analytes was established: total bilirubin (+10,5%), ALT activity (±13,4%), AST activity (+11,1%) and creatinine (+51,4%). The alterations of indices up to level of ±10% and higher are clinically significant and have to be taking into account by physicians of clinical laboratory diagnostic and clinical physicians during interpretations of the results of biochemical analysis of blood for evaluation of true picture of condition of patient. The AB0-group specific characteristics of biochemical analysis of blood are established in conditions of hyperglycemia. The hyperglycemia is an interfering factor during implementation of laboratory analysis that is especially actual at interpretations of results of biochemical analysis of blood in patients of reanimation department and individuals suffering of persistent and severe diabetes mellitus with its complication with nephropathy. Besides, the established group-specific characteristics of hyperglycemia effecting the results of biochemical analysis of blood can be accounted in development of standards and guidelines of personified medicine.


Theoretical study of the dissociation of nitric acid at a model aqueous surface.
The issue of acid dissociation of nitric acid at an aqueous surface is relevant in various portions of the atmosphere in connection with ozone depletion. This proton-transfer reaction is studied here via electronic structure calculations at the HF/SBK+(d) level of theory on the HNO(3) x (H(2)O)(3) model reaction system embedded in clusters comprising 33, 40, 45, and 50 classical, polarizable waters with an increasing degree of solvation of the nitrate group. Free energy estimates for all the cases examined favor undissociated, molecular nitric acid over the 0-300 K temperature range, including that relevant for the upper troposphere, where it is connected to the issue of the mechanism of nitric acid uptake by water ice aerosols. The presence of molecular HNO(3) at 300 K at the surface is further supported by vibrational band assignments in good agreement with a very recent surface-sensitive vibrational spectroscopy study of diluted HNO(3)/H(2)O solutions.


CD25 expression and outcomes in older patients with acute myelogenous leukemia treated with plerixafor and decitabine.
We investigated CD25 expression in older (≥60 years) patients with new acute myelogenous leukemia treated with decitabine and plerixafor. Patients resistant to therapy or survival ≤1 year had significantly higher percentages of CD25pos myeloid blasts in baseline bone marrow. CD25pos patients had an increased odds of resistance compared to CD25neg patients (p = .015). In univariate analysis, we found CD25pos patients had inferior survival compared to CD25neg (p = .002). In patients with intermediate risk cytogenetics, CD25pos status stratified patients associating with inferior survival (p = .002). In multivariable analysis, CD25 and TP53 mutations trended towards predicting remission to therapy but were not predictive of survival. Only remission status, ASXL1 and TET2 mutations were found to independently predict overall survival (OS). We conclude CD25 expression identifies patients at risk for resistance to hypomethylating chemotherapy but does not independently predict OS in an older AML population treated with decitabine and plerixafor.


Repair of huge left ventricular pseudoaneurysm after sutureless repair.
A 72-year-old man underwent sutureless repair of an oozing-type left ventricular free wall rupture. Echocardiography 8 months after sutureless repair revealed a huge left ventricular pseudoaneurysm and severe mitral regurgitation (MR). Therefore, left ventricular reconstruction and restrictive mitral annuloplasty were performed. The patient's clinical condition was improved and no residual MR has been detected for 12 months. We conclude that left ventricular reconstruction and restrictive mitral annuloplasty could be useful for left ventricular pseudoaneurysm with MR.


Total synthesis and anti-viral activities of an extract of Radix isatidis.
Radix isatidis (Banlangen), a famous traditional Chinese medicine, has been used for thousands of years in China due to its anti-viral activity. Through our research, we inferred that the anti-viral activity of Radix isatidis depended on the water-soluble part. Among the components of this extract, the isoquinoline derivative 1 was isolated for the first time and has shown better anti-viral activity than other constituents. In this study, to solve the problem of sourcing sufficient quantities of compound 1, a total synthesis route is described, and several analogues are also evaluated for their anti-viral activities. Among them, compound 8 shown potent anti-viral activity with an IC50 value of 15.3 µg/mL. The results suggested that isoquinoline derivatives possessed potent anti-viral activity and are worthy further development.


Health inequalities and inadequate housing: the case of exceptions to hygienic requirements for dwellings in Italy.
In the past decades, Italian hygienic requirements for dwellings have been modified by multiple derogations. Aim of the present work is to analyse the derogations introduced at a national, regional, and local level. The most important derogations were related to the habitable use of semi-basements and garrets, and building restoration. The paper also describes the regulations regarding indemnity for infringement of building abuses. The authors underline the need for more uniformity and clarity in the determination of health standards of dwellings, as well as for a simplification of the existing legislation.