Distribution of respiratory syncytial virus subtypes A and B among infants presenting to the emergency department with lower respiratory tract infection or apnea.
Respiratory syncytial virus (RSV), a leading viral respiratory pathogen worldwide, has 2 major subtypes, A and B. To describe the temporal and geographic distribution and parameters of disease severity associated with RSV A and B in the United States. A US multicenter active surveillance study was conducted in emergency departments (EDs) during 2 RSV seasons. Infants <1 year of age presenting to the ED with symptoms of lower respiratory tract infection or apnea were enrolled. RSV subtypes were detected in nasal swabs by reverse transcriptase polymerase chain reaction. Of 4248 patients enrolled, 4172 patients were evaluable; 32.4% of patients were positive for any RSV subtype in season 1 and 29.9% in season 2. RSV A and B were detected in each region studied. More patients presented to the ED with RSV A than with RSV B (853 [20.4%] versus 453 [10.9%], respectively); RSV A-positive patients were more likely to be admitted to the hospital or intensive care unit (47.7%, versus RSV B, 35.8%; P < 0.0001); hospitalized RSV A-positive patients were less likely to be prescribed antibiotics (32.4%, versus RSV B, 47.8%; P < 0.001). This is the largest epidemiologic study in EDs reporting trends in RSV subtypes. RSV subtypes A and B were documented in both seasons across all US regions studied and detected in September to May. The results of this study support suggestions from smaller studies that RSV A may be more virulent than RSV B; however, more quantitative assessments of disease severity are needed.


Association of 3-dimensional facial changes and height and weight increase in children: A 2-year follow-up.
This study aimed to evaluate changes in facial size and shape in children and their relationship to the changes in height and weight. One hundred and thirteen healthy children aged between 6 and 13 years were followed annually for 2 consecutive years. The facial morphology was captured in 12-month intervals (from T1 to T2 and from T2 to T3) using a 3-dimensional stereophotogrammetric optical scanner; the body height and weight were recorded simultaneously. The changes in facial size and shape were analyzed with geometric morphometrics. Multiple regression mixed-effects models were exploited for evaluation of the association between the changes of facial size or shape and age at the beginning of the observation, gender, and change of height and weight. The centroid size (reflecting facial size) increased from T1 to T2 and T2 to T3 in boys and girls. In contrast, the facial shape did not change during both 12-month observation periods (T1 to T2 and T2 to T3) either in boys or girls. Of 2 multiple regression mixed-effects models, only the model with the change of natural logarithm of centroid size as a dependent variable was statistically significant (P <0.001; adjusted r2 = 0.29). It showed that height and weight changes were associated with a change of the facial size (with weight change having a greater effect than height change: adjusted r2 = 0.25 for weight change and adjusted r2 = 0.106 for height change). Most changes in the facial morphology observed in our cohort were associated with increasing facial size. In contrast, the shape of the face remained relatively constant. Body height and weight gains were associated with the change of the facial size only. However, only 29% of the variation in facial size was explained by height or weight changes during growth.


High perilymphatic potassium and rubidium levels modulate the sensory resting discharge in the isolated frog labyrinth.
The effects of high perilymphatic K+ and Rb+ concentrations (20 mM) on the posterior canal resting discharge have been examined in the isolated frog labyrinth. Both K+ and Rb+ produced an increase in spike frequency which is sustained by a parallel increase in the excitatory postsynaptic potential (EPSP) emission rate. High K+ and Rb+ levels reduce the size of the afferent spike, broaden its time course but do not induce repetitive activity at the axon level. The K+ and Rb+ facilitation proved to be inversely related to the fibre's initial resting activity. The facilitation produced by increased K+ was usually larger than that in Rb+ solution. High sensitive and low sensitive units with similar low resting discharge were detected in relation to their response either to K+ or Rb+. The effects of both ions can be explained on the basis of their interactions with the presynaptic hair cell currents.


Maturation of neurotransmission at cholinergic synapses formed in culture by rat retinal neurons: regulation by cyclic AMP.
The objective of this study was to investigate how the maturation of neurotransmission is regulated. We used a retina-muscle cell culture system to explore the effects of cyclic AMP analogues on the developmental step in which a presynaptic neuron acquires the ability to transmit excitatory information across a synapse. Cholinergic neurons dissociated from the perinatal rat retina form synapses in culture with rat striated muscle cells. Early in the functional maturation of these retina-muscle synapses, there is a period in which the release of acetylcholine occurs spontaneously, but cannot be evoked. This stage is followed by the emergence of transmitter release that is stimulus-evoked. We report here that exposure of cultured embryonic neurons of the rat retina to 8-bromo-cyclic AMP precociously induced in these neurons the ability to release acetylcholine at synapses in response to excitatory stimulation. This effect on synaptic development could be mimicked by an inhibitor of phosphodiesterase, isobutylmethylxanthine. The results of a variety of experiments lead us to propose that 8-bromo-cyclic AMP may accelerate the development of neurotransmission by influencing presynaptic events linking neuronal depolarization with acetylcholine release. Our data support the hypothesis that cyclic AMP may be an intracellular mediator for developmental signals which regulate the emergence of effective neurotransmission across nascent synapses.


Surgery First and Surgery Early Treatment Approach in Orthognathic Surgery.
We have observed a revival of the original Surgery First approach in orthognathic surgery. Fully digital planning and simulation of the surgery has improved the predictability of Surgery First procedures. The orthodontist plays a crucial role in the successful management of Surgery First and Surgery Early cases. Surgery First and Surgery Early procedures have made the correction of a dentofacial deformity and dysgnathia a clear and transparent procedure. The decision of the treatment protocol is based on a thorough consideration and discussion between the surgeon, the orthodontist, and the patient for a successful outcome.


ALICE: a randomized placebo-controlled phase II study evaluating atezolizumab combined with immunogenic chemotherapy in patients with metastatic triple-negative breast cancer.
Immunotherapy with checkpoint inhibitors (CI) represents an important novel development in cancer treatment. Metastatic triple-negative breast cancer (mTNBC) is incurable, with a median survival of only ~ 13 months. We have initiated the randomized placebo-controlled phase IIb study ALICE, evaluating PD-L1 blockade combined with immunogenic chemotherapy in mTNBC patients (n = 75). Intriguingly, the host immune response is strongly predictive for the effect of chemotherapy in mTNBC. In the ALICE trial, we release the brake on the immune response by use of atezolizumab, an inhibitory antibody against PD-L1. We utilize anthracyclines, shown to trigger the immune system, and low-dose cyclophosphamide, which has been reported to counter immunosuppressive cells. ALICE is a randomized, double-blind, placebo-controlled exploratory phase II study evaluating the safety and efficacy of atezolizumab when combined with immunogenic chemotherapy in subjects with mTNBC. The trial will enroll 75 evaluable subjects, randomized 2:3 into two arms (A:B). The patients receive identical chemotherapy, i.e. pegylated liposomal doxorubicin (PLD 20 mg/m2 intravenously every 2nd week) + cyclophosphamide (50 mg per day, first 2 weeks in each 4 week cycle). Patients in arm A receive placebo, while patients in arm B receive atezolizumab. The primary objectives are assessment of toxicity and progression-free survival. The secondary objectives include overall survival, tumor response rate, clinical benefit rate, patient reported outcomes, biomarkers and assessment of tumor-immune evolution during therapy. The question of how CI should be combined with chemotherapy, is a key challenge facing the field. There is a strong preclinical rationale for exploring if anthracyclines, which are considered to induce immunogenic cell death, synergize with PD-L1 blockade, and if low-dose cyclophosphamide counters tumor tolerance. However, the data from patients is as yet very limited, and the clinical evaluation of these hypotheses is among the key objectives in the ALICE trial. The study includes extensive biobanking and translational sub-projects, also addressing other clinically important questions. These analyses may uncover mechanisms of drug efficacy or tumor resistance, and identify biomarkers allowing personalized therapy. If the trial suggests acceptable safety of the ALICE therapy and provide a signal of clinical efficacy, further studies are warranted. Trial registration NCT03164993, May 24th 2017; https://clinicaltrials.gov/ct2/show/record/NCT03164993.


Mediastinal schwannoma: A case report.
Mediastinal schwannoma is a rare tumor that develops from a peripheral nerve sheath in the mediastinal. An Indonesian female, 60 years old, complained of breathlessness, left chest pain, and an intermittent cough. A cystic lesion in the left lung was discovered on radiological evaluation and no evidence of malignancy or metastases were found. The patient underwent a thoracotomy and continued therapy, which included cefixime at a dose of 2 × 200 mg/day, ketorolac at a dose of 3 × 30 mg/day, ranitidine at a dose of 2 × 50 mg/day, and wound care. Histopathology examination revealed a mediastinal schwannoma. For 3 months, the patient-controlled dyspnea, left chest pain, and intermittent cough disappeared once a month. If the tumor is large enough, a thoracoscopic procedure is advised. Because mediastinal schwannomas are benign tumors, most do not get radiotherapy, chemotherapy, and recurrence in this case has not been reported. Tissue histopathology is used to determine the diagnosis mediastinal schwannoma, whereas radiological evaluation just confirms the diagnosis. The management is thoracotomy for large masses.


Effect of sodium chloride on solute-solvent interactions in aqueous polyethylene glycol-sodium sulfate two-phase systems.
Partition behavior of eight small organic compounds and six proteins was examined in poly(ethylene glycol)-8000-sodium sulfate aqueous two-phase systems containing 0.215M NaCl and 0.5M osmolyte (sorbitol, sucrose, TMAO) and poly(ethylene glycol)-10000-sodium sulfate-0.215M NaCl system, all in 0.01M sodium phosphate buffer, pH 6.8. The differences between the solvent properties of the coexisting phases (solvent dipolarity/polarizability, hydrogen bond donor acidity, and hydrogen bond acceptor basicity) were characterized with solvatochromic dyes using the solvatochromic comparison method. Differences between the electrostatic properties of the phases were determined by analysis of partitioning of sodium salts of dinitrophenylated (DNP-) amino acids with aliphatic alkyl side-chain. The partition coefficients of all compounds examined (including proteins) were described in terms of solute-solvent interactions. The results obtained in the study show that solute-solvent interactions of nonionic organic compounds and proteins in polyethylene glycol-sodium sulfate aqueous two-phase system change in the presence of NaCl additive.


Unexplained persistent postpartum palpitations and tachycardia due to Group A Streptococcus.
Group A Streptococcus is one of the most morbid infections in modern obstetric practice. Pregnant women are known to have a 20-fold increased risk of invasive Group A Streptococcus with greatest risk in the first 4 days postpartum. The overwhelming majority of these infections will present with fever, uterine tenderness, or vaginal discharge. A much smaller subset may present to the Emergency Room after initial hospital discharge with much less obvious symptoms. In our case, persistent palpitations with unexplained tachycardia led to improper diagnosis in multiple Emergency Rooms. A 37 year-old Caucasian female presents with four post-partum days of unexplained sinus tachycardia and absence of fever, uterine tenderness, or vaginal discharge, which elicits an extensive cardiac and pulmonary workup in multiple Emergency Rooms. Consequent late diagnosis of invasive Group A Streptococcus infection lead to significantly increased morbidity including toxic shock syndrome, acute renal failure, total abdominal hysterectomy and bilateral salpingo-oophorectomy, multiple laparotomies, fasciotomy, intubation, continuous renal replacement therapy, and extensive hospital course and recovery. Persistent palpitations with unexplained tachycardia in the post-partum patient in the Emergency Room setting is a potential early warning of Group A Streptococcus infection. Even in the absence of reported clinical fever, uterine tenderness, or vaginal discharge, an early speculum and pelvic exam, with or without consultation with the obstetrics service, is prudent due to the potentially high morbidity or even fatality of Group A Streptococcus infection.


SRT1720 plays a role in oxidative stress and the senescence of human trophoblast HTR8/SVneo cells induced by D-galactose through the SIRT1/FOXO3a/ROS signalling pathway.
D-galactose (D-gal) is a reducing sugar widely distributed in food. In a pregnant animal model exposed to D-gal, D-gal was found to have toxic effects on both the mother and foetus through oxidative stress. However, little is known about the effect of D-gal exposure on the placenta and its underlying mechanism. In this study, we evaluated the effects of D-gal on HTR8/SVneo cells and the mechanisms in vitro. In the present study, the activity of HTR8/SVneo human trophoblasts decreased in a time- and concentration-dependent manner after exposure to D-gal. D-gal resulted in premature senescence of HTR8/SVneo cells, as confirmed by assessing β-galactosidase (SA-β-gal) activity and the expression of senescence-related factor p21. We also verified the damage of oxidative stress induced by D-gal by measuring the expression of reactive oxygen species (ROS), sirtuin 1 (SIRT1) and forkhead box O (FOXO) 3a. SRT1720, as a SIRT1 activator, mitigated D-gal-induced oxidative stress and senescence by upregulating SIRT1 and FOXO3a expression and reducing ROS production. Our data suggest that D-gal may induce HTR8/SVneo premature ageing through the SIRT1/FOXO3a/ROS signalling pathway mediated by oxidative stress and that SIRT1 protects cells from this damage.


The Amadori rearrangement as key reaction for the synthesis of neoglycoconjugates.
The Amadori rearrangement was introduced as a key step for the conjugation of carbohydrate moieties with suitable amines such as aliphatic amines and amino acid derivatives. The rearrangement products were further transformed into the corresponding 1-N,2-O cyclic carbamates employing triphosgene to obtain anomerically stable glycoconjugates. The reaction conditions were probed on a model substrate, 3,5-di-O-benzyl-alpha,beta-d-glucofuranose and further applied to d-glycero-d-gulo-heptose, which gave 'd-gluco-conjugates' in the alpha-anomeric form exclusively in high isolated yields.


Arachnoid cysts: computed tomography findings.
Described are 26 cases of arachnoid cysts. Of these cysts, 54% were in the sylvian cistern, three (1.2%) were in the suprasellar cistern, and the rest were over the cerebral sulci. There were symptoms of seizures at presentation in 30.8%, and in 23% there were symptoms of hydrocephalus and compression of the brain. A total of 61.5% presented with mental retardation and/or cerebral palsy. Trauma and infection accounted for 35% of these cysts. Associated porencephaly were present in five cases. There was a male preponderance. Left-sided lesions accounted for 61.5% of the lesions. The radiologic appearances, especially of suprasellar cysts, and the differential diagnoses of these lesions are discussed. Their recognition and the role of surgery are stressed.


Genetic analysis of HLA-DRA region variation in Taiwanese Parkinson's disease.
Parkinson's disease (PD) is a neurodegenerative disorder comprising both motor and cognitive disability. The pathogenesis of the disease is still unclear; however, neuroinflammation seemed to play a role. A recent genome-wide association study (GWAS) reported an association between HLA-DRA rs3129882 and the development of PD in Caucasian populations. In this study, we observe no association between this single nucleotide polymorphism and PD in a Taiwanese population. The possible reasons include different ethnicity with genomic differences and environmental factors in different geographical regions.


Engineering cyclodextrin glycosyltransferase into a starch hydrolase with a high exo-specificity.
Cyclodextrin glycosyltransferase (CGTase) enzymes from various bacteria catalyze the formation of cyclodextrins from starch. The Bacillus stearothermophilus maltogenic alpha-amylase (G2-amylase is structurally very similar to CGTases, but converts starch into maltose. Comparison of the three-dimensional structures revealed two large differences in the substrate binding clefts. (i) The loop forming acceptor subsite +3 had a different conformation, providing the G2-amylase with more space at acceptor subsite +3, and (ii) the G2-amylase contained a five-residue amino acid insertion that hampers substrate binding at the donor subsites -3/-4 (Biochemistry, 38 (1999) 8385). In an attempt to change CGTase into an enzyme with the reaction and product specificity of the G2-amylase, which is used in the bakery industry, these differences were introduced into Thermoanerobacterium thermosulfurigenes CGTase. The loop forming acceptor subsite +3 was exchanged, which strongly reduced the cyclization activity, however, the product specificity was hardly altered. The five-residue insertion at the donor subsites drastically decreased the cyclization activity of CGTase to the extent that hydrolysis had become the main activity of enzyme. Moreover, this mutant produces linear products of variable sizes with a preference for maltose and had a strongly increased exo-specificity. Thus, CGTase can be changed into a starch hydrolase with a high exo-specificity by hampering substrate binding at the remote donor substrate binding subsites.


Family planning and the future.
The adoption of Title X in 1971 provided for public funding for family planning in the United States but funding from this program has not kept pace with demand for contraceptives. In 1997, The California Department of Public Health established the Family Planning, Access, Care, and Treatment (PACT) Program, a public-private partnership to meet the needs of Californians, including about a half-million adolescents, who did not have access to contraceptive services. The program has saved the state billions of dollars in maternity and abortion costs, dramatically reduced teen pregnancy rates, and serves as a good example for other states.


Generation of terahertz radiation by hot electrons in carbon nanotubes.
We demonstrate theoretically that quasi-metallic carbon nanotubes emit terahertz radiation induced by an applied voltage. It is shown that in the ballistic transport regime their spontaneous emission spectra have a universal frequency and bias voltage dependence, which raises the possibility of utilizing this effect for high-frequency nanoelectronic devices.


Management of scleral tears with concurrent intraocular foreign bodies and factors affecting outcomes.
To report the clinical settings and factors predicting outcomes in scleral tears with concurrent retained intraocular foreign bodies METHODS: All cases with scleral and corneoscleral wounds with retained intraocular foreign bodies (RIOFB) from January 2014 to January 2021 were retrospectively analysed. Favourable anatomic outcome was defined as presence of globe integrity, attached retina, absence of hypotony and active inflammation at last visit. Favourable functional outcome was defined as final visual acuity (VA) > 20/200. Total 139 eyes were included. Mean age was 30.66 ± 13.32 years (median 29 years, IQR 17). Penetrating trauma accounted for 87.1%, rupture for 5.8%, perforation for 7.2%. In 5.8% of the eyes the injury involved zone I extending till Zone II while in 66.9% it involved Zone II and in 27.3% in Zone III. Snellen visual acuity at presentation was logMAR 2.97 ± 1.01 and at last visit was logMAR 2.38 ± 1.45 (p < 0.0001). Time between presentation and repair was 13.93 ± 19.56 h (median 7.6 h, IQR 17.17). Favourable functional outcome was seen in 34.5% eyes and 2/3rd achieved favourable anatomic outcome. Absence of endophthalmitis (OR = 6.25, p = 0.003) and ability to remove the foreign body (OR = 7.05, p = 0.003) were associated with a favourable anatomic outcome. Better presenting Snellen visual acuity (OR = 2.77, p = 0.003), manifest scleral tear (OR = 3.36, p = 0.04), and absence of endophthalmitis (OR = 50, p = 0.0009) were associated with a favourable functional outcome. A third of the cases achieved favourable visual outcome while 2/3rd achieved favourable anatomic outcome. Absence of endophthalmitis is an important factor predicting both.


Auditory brain-stem responses in Marcus Gunn ptosis.
The auditory brain-stem response (ABR) can detect anomalies both in the auditory pathways and in structures adjacent to these pathways. Patients with Duane's retraction syndrome, associated with hypoplasia of the abducens nerve in the brain-stem, and patients with hemifacial spasm, due to compression of the facial nerve in the brain-stem, have been found to have abnormal ABRs. Marcus Gunn ptosis with 'jaw winking' is considered to be due to misconnection of oculomotor, trigeminal and other cranial nerves. Suspecting that perhaps some 'jaw-winking' phenomena may be due to detectable brain-stem anomalies we tested 7 patients with Marcus Gunn ptosis. Three of the patients demonstrated abnormal ABRs indicative of pontine pathology.


Maintaining love and hope: caregiving for Thai children with HIV infection.
In this grounded theory study, the author explored how primary caregivers dealt with problems in caring for children with HIV infection in Thailand. A total of 27 family caregivers of HIV-infected children participated in open-ended interviews. Maintaining love and hope represented a condition for the continuing process of caregiving. Caregivers had to deal with the stigma of AIDS while providing care for children with HIV. They had high anxiety and fear of loss, bore much burden of care, and faced many difficulties because of limited resources. The results suggest that psychosocial care and informational support are needed to enable these caregivers to provide better care for children with HIV infection.


Repurposing FDA Approved Drugs as JNK3 Inhibitor for Prevention of Neuroinflammation Induced by MCAO in Rats [Retraction].
[This retracts the article DOI: 10.2147/JIR.S284471.].


Hemorrhage Occluder™ Pin to control life-threatening bleeding during the removal of an infected sacrocolpopexy mesh: A case report.
Vaginal mesh exposures and infections are recognized complications of open and laparoscopic sacrocolpopexy performed for vault prolapse. In severe cases, complete sacrocolpopexy mesh removal may be necessary. This case report presents a 72-year-old woman with previous mesh sacrocolpopexy who presented with infected mesh and recurrent vaginal bleeding despite multiple attempts at surgical transvaginal mesh excision. A life-threatening massive hemorrhage occurred intra-operatively. After several failed attempts to control bleeding, hemorrhage Occluder™ Pins were successfully placed by vascular surgery to control presacral veins. Although an exceedingly rare complication, anticipation and rapid management of life-threatening bleeding are critical to save life during complicated mesh removals.


The impact of mitochondrial tRNA mutations on the amount of ATP synthase differs in the brain compared to other tissues.
The impact of point mutations in mitochondrial tRNA genes on the amount and stability of respiratory chain complexes and ATP synthase (OXPHOS) has been broadly characterized in cultured skin fibroblasts, skeletal muscle samples, and mitochondrial cybrids. However, less is known about how these mutations affect other tissues, especially the brain. We have compared OXPHOS protein deficiency patterns in skeletal muscle mitochondria of patients with Leigh (8363G>A), MERRF (8344A>G), and MELAS (3243A>G) syndromes. Both mutations that affect mt-tRNA(Lys) (8363G>A, 8344A>G) resulted in severe combined deficiency of complexes I and IV, compared to an isolated severe defect of complex I in the 3243A>G sample (mt-tRNA(LeuUUR). Furthermore, we compared obtained patterns with those found in the heart, frontal cortex, and liver of 8363G>A and 3243A>G patients. In the frontal cortex mitochondria of both patients, the patterns of OXPHOS deficiencies differed substantially from those observed in other tissues, and this difference was particularly striking for ATP synthase. Surprisingly, in the frontal cortex of the 3243A>G patient, whose ATP synthase level was below the detection limit, the assembly of complex IV, as inferred from 2D-PAGE immunoblotting, appeared to be hindered by some factor other than the availability of mtDNA-encoded subunits.


Understanding the meaning of the shunt fraction calculation.
The pulmonary shunt fraction (Qs/Qt) is frequently calculated in critically ill patients to monitor the effectiveness of pulmonary oxygenation. The breathing of pure oxygen often results in higher calculated Qs/Qt values that have been attributed to the development of atelectasis, ventilation-perfusion imbalance, or both. To interpret properly the changes in calculated Qs/Qt that occur when the inspired oxygen fraction is altered, the changes produced in all the variables affecting Qs/Qt must be known. This tutorial presents an in-depth analysis of the four variables affecting the calculation of Qs/Qt: VO2 (oxygen uptake), Qt (cardiac output), Cc'O2 (oxygen content in pulmonary end capillaries), and CvO2 (oxygen content in mixed venous blood). These variables are related according to the following equation, which is derived by combining the Fick and the classic shunt equations: Qs/Qt = 1 - [(VO2/Qt)/(Cc'O2 - CvO2)]. Three-dimensional surface representations relating these variables are also presented to help the reader understand the effects of these variables on the calculated Qs/Qt.


3D Tumor Models and Time-Lapse Analysis by Multidimensional Microscopy.
The 3D culture is advantageous in reflecting the in vivo condition compared to the 2D culture; however, imaging 3D-cultured cells may be a challenge due to technical restrictions. Recent development of confocal spinning disc microscope system as well as sophisticated software has enabled us to monitor dynamism of cell movement in multiple dimensions. Here we describe the method for time-lapse imaging of 3D-cultured cancer cells co-cultured with non-cancerous cells and discuss current limitations and future perspectives.


Use of Stem Cells for the Treatment of Musculoskeletal Injuries in Horses.
Mesenchymal stem cells (MSCs) are used as a regenerative therapy in horses for musculoskeletal injury since the late 1990s and in some regions are standard of care for certain injuries. Yet, there is no Food and Drug Administration-approved MSC therapeutic in the United States for horses. In humans, lack of regulatory approval in the United States has been caused by failure of late-phase clinical trials to demonstrate consistent efficacy, perhaps because of nonuniformity of MSC preparation and application techniques. This article discusses clinical evidence for musculoskeletal applications of MSCs in the horse and current challenges to marketing approval.


Reply to van Lingen et al. Comment on "Szczubełek et al. Effectiveness of Crohn's Disease Exclusion Diet for Induction of Remission in Crohn's Disease Adult Patients. Nutrients 2021, 13, 4112".
Thank you for your comment and interest [...].


Sex Differences in the Pathophysiology, Diagnosis, and Management of Aortic Stenosis.
For years, calcific aortic stenosis (AS) was considered to be similar in men and women, and the underrepresentation of women in research studies prevented any alternate conclusions. With new sex-specific studies and data, the landscape of AS is evolving and recently important sex-disparities were revealed. These sex-specific discrepancies are of utmost importance to stratify and personalize treatment according to sex. It is important and urgent to elucidate the sex-related differences and similarities in the pathophysiology of AS to develop and validate sex-specific approaches for the management and pharmacologic treatment of AS, and to improve clinical outcomes for both sexes.


Synthesis of [(2'S, 3'S)-bis(hydroxylmethyl)pyrrolidin-1-yl] purine and pyrimidine nucleosides as potential antiviral agents.
The enantiomerically pure synthesis of [(2'S, 3'S)-bis(hydroxymethyl)pyrrolidin-1-yl] thymine 17 and -adenine 20 was achieved via construction of the base on the 1-amino-pyrrolidine 15, and their anti-HSV-1 and -2, and anti-HIV-1 activities were evaluated.


Borrelia burgdorferi inhibits NADPH-mediated reactive oxygen species production through the mTOR pathway.
Redox metabolism is crucial in host defense. Previously, it was shown that Borrelia burgdorferi induces the antioxidative metabolism in primary human monocytes. In this study, we explore how B. burgdorferi affects the anti-oxidative arm of redox metabolism, i.e. the generation of reactive oxygen species (ROS). Peripheral blood mononuclear cells (PBMCs) were exposed to B. burgdorferi and generation of ROS was determined both after acute stimulation and after re-stimulation with a secondary stimulus. Though the spirochete induces very low levels of ROS itself, it dramatically decreases the long-term capacity of PBMCs to generate ROS in response to serum-opsonized zymosan (SOZ). This was followed by a compensatory overshoot in ROS generation at later time points. The PI3K/Akt pathway and intracellular levels of methionine play an important regulatory role in this process. Dysregulation of oxidative metabolism may be a novel mechanism by which the spirochete modulates the human immune system and evades killing.


Vaccinia virus-induced apoptosis in immature B lymphocytes: role of cellular Bcl-2.
Apoptosis is a form of physiological cell death which can be initiated in response to various stimuli including virus infections. We show that vaccinia virus (VV) infection induces apoptosis in an immature B lymphocyte line, WEHI-231. In these cells, several VV-specific proteins were synthesized during the infection, but neither virus production nor viral DNA synthesis were detected. The intracellular levels of the proto-oncogene Bcl-2, which effectively protects cells from programmed cell death, were found to be down-regulated by the VV infection, suggesting that this down-regulation might be involved in the viral induction of apoptosis in WEHI-231 cells. Stable transfectants overexpressing human Bcl-2 were shown to be resistant to the apoptosis produced by the infection, a finding consistent with the proposed role for the down-regulation of endogenous Bcl-2 in VV-induced apoptotic death.


The wear of high-carbon metal-on-metal bearings after different heat treatments.
To study the tribological performance of metal-on-metal hip joint resurfacings, the wear performance of three pairs of Co-Cr-Mo alloy samples (pins and plates) were tested in a multidirectional pin-on-plate wear machine. An 'as-cast', a single-heat-treated, and a double-heat-treated set of specimens were tested to 3 x 10(6) cycles. The two heat treatments resulted in partial and full solution of the carbides into the matrix. An increasing trend in wear rate was found from 'as-cast' to the double-heat-treated specimens. The as-cast specimens showed the lowest wear rate (1.69 x 10(-6) mm3/N m), the reduced carbide samples had the next lowest wear rate (2.1 x 10(-6) mm3/N m), while the specimens without carbides wore the most (2.41 x 10(-6) mm3/N m).


Organization and morphological characteristics of choline acetyltransferase-containing fibers in the visual thalamus and striate cortex of the cat.
The morphological characteristics and the distribution of cholinergic fibers in the cat visual system were studied with immunohistochemical methods employing monoclonal antibodies directed against choline acetyltransferase (ChAT). ChAT-positive fibers form dense meshworks within the main laminae of the dorsal lateral geniculate nucleus (LGNd), the perigeniculate nucleus (PGN) and the visual cortex. The fibers are of fine caliber, branch extensively and possess numerous varicosities in close contact with cellular elements. The density of ChAT + fibers is not uniform and is particularly high in cortical laminae I-III, the PGN complex and laminae A and A1 of the LGNd.


Enantiomeric separation of amide derivatives of some 2-arylpropionic acids by HPLC on a cellulose-based chiral stationary phase.
A reversed phase high-performance liquid chromatographic method has been developed for the determination of the R- and S-enantiomers of ibuprofen, flurbiprofen, ketoprofen and tiaprofenic acid. Separation has been achieved using a tris(4-methylbenzoate)cellulose phase after derivatization into their amides. Flurbiprofen could also be partially resolved into its enantiomers without prior derivatization.


Ectopic expression of chloramphenicol acetyltransferase (CAT) in the cerebellum in mice transgenic for a carbonic anhydrase II promoter-CAT construct that is without apparent phenotypic effect.
We have developed six transgenic lines of mice with constructs containing presumptive 5' regulatory regions of carbonic anhydrase II (CA II). Four of the lines contained 1,100 bases of the 5' flanking region of the human CA II gene, and two transgenic lines resulted from a construct containing 500 bases of the 5' flanking region of the mouse CA II gene. Tissue-specific expression of the chloramphenicol acetyltransferase (CAT) gene was not obtained in any of the transgenic lines. One of the transgenic lines was found to have high levels of expression of CAT in cerebellum. This expression persisted through multiple generations and was independent of the parental origin of the transgene. On the assumption that the expression was due to the insertion of the transgene in or near a gene expressed normally in cerebellum, homozygous mice were bred for the transgenic insert to see if a mutation might have been induced. Homozygous mice were found and seemed to be normal in all aspects of their phenotype studied. Thus, in this case, neither the insertion of the gene nor the ectopic expression of CAT seemed to be harmful to the animals.


Sagittal abdominal diameter to triceps skinfold thickness ratio: a novel anthropometric index to predict premature coronary atherosclerosis.
We aimed to compare the accuracy of a novel index defined by us, as a ratio of Sagittal abdominal diameter (SAD) and triceps skinfold thickness (TSF) with other indices of adiposity for prediction of presence, severity and extension of premature coronary artery disease (CAD). A cross-sectional study was conducted on 238 younger patients (females <55 years; males <45 years) who underwent coronary angiography. Anthropometric indices including TSF, SAD, waist circumference, and hip circumference were measured before catheterization and body mass index, waist-to-hip ratio, abdominal diameter index, index of central obesity as well as our proposed index, SAD-to-TSF ratio, were calculated accordingly. Evaluation of severity and extension of coronary stenosis was by Gensini score and extent score, respectively. After adjustment for age and sex in multivariate regression models, the SAD-to-TSF ratio was the best predictor for the presence (OR = 2.49, 95% CI = 1.44-4.30; p = 0.001) and extension (β = 1.10, p = 0.004) of premature CAD. TSF and the SAD-to-TSF ratio were the only indices that significantly predicted the Gensini score and the correlation remained significant even after adjustment for age and sex (β = -7.28, p < 0.0001 and β = 3.76, p < 0.0001, respectively). We showed that our proposed index, SAD-to-TSF ratio, has a substantially better accuracy than do the known indices of obesity like body mass index, waist circumference, and waist-to-hip ratio for the prediction of premature CAD. Furthermore, our index was the only index that positively correlated with the severity of premature CAD.


Axonal transport dysfunction in dystrophia myotonica.
Axonal transport of acetylcholinesterase (AChE) was measured in the median and sural nerves of a subject who suffered from dystrophia myotonica and in a control subject. It was found that the basal activity of AChE was increased in myotonic nerves while its proximodistal transport was inhibited.


Experiences of midwives regarding provision of culturally competent care to women receiving maternal care in South Africa.
Due to the cultural diversity in South Africa, midwives are challenged to provide culturally competent, congruent, and sensitive maternal care. Using a qualitative descriptive design, this study aimed to explore and describe the experiences of midwives providing culturally competent care to women receiving maternal care within overburdened public hospitals. Purposive sampling of thirty-four (n = 34) midwives employed to provide maternal care (antenatal, intrapartum, and postpartum) at five public hospitals in the North West Province of South Africa was done. Semi-structured interviews were conducted in English and transcribed verbatim. Data was analysed thematically with the assistance of an independent co-coder. Data revealed that midwives viewed communication as a key component of cultural competence. Midwives do not necessarily understand the concept "cultural competence." It is recommended that a policy of culturally competent maternal care be developed and implemented by midwives in practice.


Coordinating Adsorption and Catalytic Activity of Polysulfide on Hierarchical Integrated Electrodes for High-Performance Flexible Li-S Batteries.
Lithium-sulfur (Li-S) batteries have been known to be a promising substitute because of their much higher theoretical energy density than that of traditional Li-ion batteries. However, the low utilization of sulfur caused by the poor conductivity of sulfur and shuttle of lithium polysulfides (LiPSs) severely restrict the commercial application of Li-S batteries, especially in flexible wearable devices. Herein, a hierarchical nitrogen-doped carbon nanotube (NCNT)@Co-Co3O4 nanowire array (NWA)-integrated electrode was developed based on the rational design of density functional theory calculations, which shows simultaneous confinement adsorption and catalysis conversion of LiPSs. In situ Raman spectra further proved that the NCNT@Co-Co3O4 NWAs exhibit sufficient adsorption capacity and high catalytic conversion of LiPSs. As a result, the NCNT@Co-Co3O4@S electrode exhibited the desirable specific capacity and excellent cyclic stability at both low and high sulfur loadings. Moreover, pouch cells with the NCNT@Co-Co3O4@S cathode show higher capacity under flat or bending states and longer cycle stability than that of the reported results. This work provides a new approach for the development of high-performance Li-S batteries toward future wearable electronics.


Reversible multiorgan system involvement in a neonate with complex IV deficiency.
Mitochondrial respiratory chain deficiencies can present as fulminant liver failure or disease, and the prognosis when associated with severe neonatal lactic acidosis is frequently guarded. We report the case of a neonate who presented with acute liver failure and fulminant lactic acidosis with profound complex IV deficiency documented in muscle and liver biopsies. The neonate subsequently experienced clinical resolution by 3 months of age, and was observed to have reversibility of the biochemical deficiency noted in muscle. This case illustrates that resolution of this severe neonatal phenotype does occur, of importance for accurate prognostic and genetic counseling for such affected neonates.


A New BRCT Binding Mode in TopBP1-BLM Helicase Interaction.
Tandem BRCT domains are phophoprotein binding modules. In this issue of Structure, Sun et al. (2017) show that a single BRCT domain in TopBP1 binds tightly and specifically to phosphorylated Bloom syndrome helicase (BLM). This work reveals a novel BRCT binding mode and suggests a similar mechanism for TopBP1 interaction with 53BP1.


Aerobic exercise and cognitive functioning in schizophrenia: A pilot randomized controlled trial.
This pilot randomized controlled trial evaluated the combined effect of individual and group aerobic exercises (AEs) on cognition in schizophrenia. Among 32 randomized patients, 31 were included in the intent-to-treat population: 16 in treatment as usual (TAU) + AE and 15 in TAU groups. Over 12 weeks, patients were given a dose of 2 exercise sessions per week, including 1 individual session and 1 group session. TAU + AE patients showed significant improvements in cognition, intrinsic motivation, psychiatric symptoms, and interpersonal relations. These encouraging findings support the promise of integrated individual and group AEs to improve cognition and other outcomes in schizophrenia.


Prostanoids in bronchoalveolar lavage fluid do not predict outcome in congenital diaphragmatic hernia patients.
Vasoactive prostanoids may be involved in persistent pulmonary hypertension (PPH) in infants with a congenital diaphragmatic hernia (CDH). We hypothesized that increased levels of prostanoids in bronchoalveolar lavage (BAL) fluid would predict clinical outcome. We measured the concentrations of 6-keto-prostaglandin F(1alpha) (6-keto-PGF(1alpha)), thromboxane B(2) (TxB(2)), protein, albumin, total cell count, and elastase-alpha1-proteinase-inhibitor complex in BAL fluid of 18 CDH patients and of 13 control subjects without PPH. We found different concentrations of prostanoids in BAL fluid of CDH patients with PPH: infants with a poor prognosis had either high levels of both 6-keto-PGF(1alpha) and TxB(2) compared to controls, or high levels of 6-keto-PGF(1alpha) only. TxB(2) levels showed a large variability in all CDH patients irrespective of outcome. We conclude that prostanoid levels in BAL fluid do not predict clinical outcome in CDH patients.


The relationship between the changes in three-dimensional facial morphology and mandibular movement after orthognathic surgery.
The purpose of this study was to investigate the relationship between changes in three-dimensional (3D) facial morphology and mandibular movement after orthognathic surgery. We hypothesized that facial morphology changes after orthognathic surgery exert effects on 3D mandibular movement. We conducted a prospective follow-up study of patients who had undergone orthognathic surgical procedures. Three-dimensional facial morphological values were measured from facial CT images before and three months after orthognathic surgery. Three-dimensional maximum mandibular opening (MMO) values of four points (bilateral condylions, infradentale, and pogonion) were also measured using a mandibular movement tracking and simulation system. The predictor variables were changes in morphological parameters divided into two groups (deviated side (DS) or contralateral side (CS) groups), and the outcome variables were changes in the MMO at four points. We evaluated 21 subjects who had undergone orthognathic surgical procedures. Alterations in the TFH (total facial height), LFH (lower facial height), CS MBL (mandibular body length), and DS RL (ramus length) were negatively correlated with changes in bilateral condylar movement. The UFH, DS MBL and CS ML (mandibular length) showed correlations with infradentale movement. The CS ML, DS ML, MBL, UFH, and SNB were correlated with pogonion movement. The height of the face is most likely to affect post-operative mandibular movement, and is negatively correlated with movement changes in the condyles, infradentale and pogonion. The changes in CS morphological parameters are more correlated with mandibular movement changes than the DS. The changes in CS MBL and bilateral RL were negatively correlated with condylar movement changes, while the bilateral MBL and CS ML were positively correlated with changes in infradentale and pogonion.


Detection of changes in the periaqueductal gray matter of patients with episodic migraine using quantitative diffusion kurtosis imaging: preliminary findings.
The periaqueductal gray matter (PAG) is considered to play an important role in generating migraine, but findings from imaging studies remain unclear. Therefore, we investigated whether diffusion kurtosis imaging (DKI) can detect changes in the PAG of migraine patients. We obtained source images for DKI from 20 patients with episodic migraine and 20 healthy controls using a 3 T magnetic resonance imaging scanner. Mean kurtosis (MK), fractional anisotropy (FA), and mean diffusivity (MD) maps were generated, and the values of the PAG and other deep gray and white matter structures were automatically measured using an atlas-based region-of-interest analysis. The metrics of these structures were compared between the patients and controls. The MK and MD values of the PAG were significantly increased in the migraine patients compared with the controls (p < 0.05). The FA values were not significantly different. There were no significant differences in the metrics of the other structures between the patients and controls. The MK values of the PAG were significantly positively correlated with both age and the untreated period in the patient group under univariate analysis (r = 0.53 and 0.56, respectively; p < 0.05) but not multivariate analysis. DKI detected significant increases in the MK and MD values of the PAG in patients with migraine, which suggests that structural changes in the PAG are associated with the pathophysiological mechanisms of migraine.


Endoscopic Screw Removal, Debridement of the Peroneal Tendons and Subtalar Joint and Lateral Calcaneal Ostectomy for Management of Chronic Heel Pain after Calcaneal Fracture.
Calcaneal fracture is one of the most common foot and ankle fractures, but the best treatment of this fracture is still under debate. No matter the treatment strategy of this intra-articular calcaneal fracture, early and late complications frequently occur. In order to treat these complications, combination of various ostectomy, osteotomy, and arthrodesis techniques have been proposed to re-establish the calcaneal height, restore the talocalcaneal relationship, and create a stable, plantigrade foot. In contrast to this approach of addressing all the deformities, another feasible approach is concentrating on those aspects that are the most clinically pressing.10, 11, 12, 13, 14, 15 Different arthroscopic and endoscopic approaches focused on the patient's symptoms and not the correction of the talocalcaneal relationship or restoration of the height or length of the calcaneus have been proposed to deal with late complications of calcaneal fractures. The purpose of this technical note is to describe the details of endoscopic screw removal, debridement of the peroneal tendons, and subtalar joint and lateral calcaneal ostectomy for management of chronic heel pain after calcaneal fracture. It has the advantage of dealing with various sources of lateral heel pain after calcaneal fracture, including the subtalar joint, peroneal tendons, lateral calcaneal cortical bulge and screws.


Balancing Patient Autonomy, Surrogate Decision Making, and Physician Non-Maleficence When Considering Do-Not-Resuscitate Orders: An Ethics Case Analysis.
[Full article available at http://rimed.org/rimedicaljournal-2017-10.asp].


Patient selection to optimize near vision performance with a low-addition trifocal lens.
To assess the impact of ocular biometric variables on the visual performance achieved with a low addition trifocal intraocular lens (MIOL). Retrospective observational study including 34 eyes. Preoperative measured variables included mean corneal power (Km), corneal regular astigmatism (RA), anterior chamber depth (ACD), axial length (AXL), total irregular astigmatism (IA), spherical aberration (SA) and distance from pupil center to vertex normal (µ). Same variables were retrieved from the three month visit follow-up in addition to the actual lens position (ALP), the calculated effective addition (EA), the IOL centration from vertex normal (d), and the visual acuity defocus curve. The area under the defocus curve was computed along the total curve (TAUC) and ranges for far (FAUC), intermediate (IAUC) and near vision (NAUC). The sample was split in two groups of 17 eyes with TAUCs above and below the mean, and the differences among groups for different ocular parameters were assessed. The group of eyes above TAUC of 2.03 logMAR*m-1 showed significantly lower Km and greater AXL and SA. Km was negatively correlated with TAUC and NAUC. NAUC was negatively correlated with IA and positively with d. A multiple lineal regression model including Km, d, and IA predicted NAUC (r-square = 34%). No significant differences between IA and SA were found between preoperative and postoperative values but µ significantly decreased after surgery. The mean corneal power, irregular astigmatism, and centration from vertex normal should be considered for optimizing the near visual performance with this MIOL.


Gravel grabs: The rocky foundations of Indigenous geologic power in the Arctic.
Infrastructure development cannot take place without gravel, which is scarce in the North American Arctic. Conditioning where development can occur, the commodity has become the target of Indigenous actors seeking to secure land and resource bases and their material futures, too. In Alaska, decades of litigation pitting Indigenous surface versus subsurface corporate landholders has contested gravel's legal location. In Canada, contrastingly, Inuvialuit land claims negotiators successfully secured access to granular resources. In both locales, legal processes have resulted in certain Indigenous actors' accumulation of geologic power. Rooted in the subterranean, this power enables them to transform the surface of the Earth. Contributing to research on geologic power and political geology and drawing on fieldwork and a review of court cases, policy documents and reports, this article critiques how gravel has become an Arctic resource lucrative to local communities rather than global markets and a key source of Indigenous political and economic agency. Going forward, struggles over Indigenous rights may concern securing ownership over not only the land base, but the land column.


Oxidative metabolism of the carcinogen 6-fluorobenzo[c]phenanthrene. Effect of a K-region fluoro substituent on the regioselectivity of cytochromes P-450 in liver microsomes from control and induced rats.
Oxidative metabolism of the carcinogen 6-fluorobenzo[c]phenanthrene (6-FB[c]Ph) was compared with that of benzo[c]phenanthrene (B[c]Ph) to elucidate the enhancement of carcinogenicity of B[c]Ph by the 6-fluoro substituent. Liver microsomes from untreated (control), phenobarbital-treated, and 3-methylcholanthrene-treated rats metabolized 6-FB[c]Ph at rates of 3.5, 1.5, and 7.7 nmol of products/nmol of cytochrome P-450/min, respectively. The rates of metabolism of B[c]Ph by the same microsomes were 2.9, 1.6, and 5.5 nmol of products/nmol of cytochrome P-450/min, respectively. Whereas the K-region 5,6-dihydrodiol was the major metabolite of B[c]Ph, the major metabolite of 6-FB[c]Ph was the K-region 7,8-oxide, which underwent slow rearrangement to an oxepin. Thus, the 6-fluoro substituent blocks oxidation at the 5,6-double bond and inhibits hydration of the K-region 7,8-oxide by epoxide hydrolase. Substitution with fluorine at C-6 caused an almost 2.5-fold increase in the percentages of the putative proximate carcinogens, i.e. benzo-ring dihydrodiols with bay-region double bonds, when liver microsomes from 3-methylcholanthrene-treated rats were used. Little or no increase was observed in their formation by liver microsomes from control or phenobarbital-treated rats. Interestingly, liver microsomes from control rats formed almost 3-fold as much 3,4-dihydrodiol as isosteric 9,10-dihydrodiol. The R,R-enantiomers of the 3,4- and 9,10-dihydrodiols and the S,S-enantiomer of the 7,8-dihydrodiol were predominantly formed by all three microsomal preparations.


Loads in hip disarticulation prostheses during normal daily use.
As a result of deficiency at birth, disease or trauma, there are people who have no limbs from the hip joint downwards. These people have no possibility of locomotion without the use of other devices such as wheelchairs or hip disarticulation prostheses. As these prostheses are used by people of all ages, people who are different in their grade of physical activities and their weights, the prostheses are subject to different stresses related to these different circumstances. The European Level 2 Draft Standard prEN 12523: 1966 "External limb prostheses and external orthoses - requirements and test methods" contains strength requirements for lower limb prostheses. These requirements shall be verified, where appropriate, by the application of the International Standard ISO 10328 "Prosthetics - Structural testing of lower limb prostheses" and ISO/FDIS 15032 "Prosthetics: Structural testing of hip prostheses". In order to allow the prostheses to be tested to the stresses that are experienced in real life, it is necessary to measure the stress that is induced in the prostheses while the patient is in an everyday situation, such as walking on level floor, walking on grass and/or walking on an uneven surface. This work is concerned with the acquisition of loads generated in hip units of hip disarticulation prostheses by amputees during various activities. More than 30 patients were tested in Germany, France, and Belgium. The measurements were carried out with financial support from the European Commission and coordinated by the secretariat of CEN TC 293.


An inventory of 13C abundances in coastal wetlands of Louisiana, USA: vegetation and sediments.
Organic carbon-rich sediments from the surface of fresh, intermediate, brackish and salt marshes of coastal Louisiana were sampled and analyzed for their 13C content. The average ∂13C from all sites within each wetland type was-27.8‰,-22.1‰,-16.9‰, and-16.2‰, for fresh, intermediate, brackish and salt marshes, respectively. Means from the fresh, intermediate and brackish marshes were significantly different at the 0.01 level. A mixing model using measurements of standing crop and ∂13C of plant carbon was applied to estimate the contribution of each species to the sedimentary carbon at four of the marsh sites. Sedimentary ∂13C values generally reflected that of the dominant species present at each site. Brackish and salt marsh samples, however, showed a negative shift of ∂13C with respect to whole plant carbon. We interpret these depeleted ∂13C values to be the result of more extensive organic matter decomposition and selective preservation of 13C-depleted refractory components in sediments from saline sites. The results of this study suggest that ∂13C composition of sedimentary carbon may offer a valuable tool for distinguishing subtle changes in paleohydrology of wetlands resulting from relative sea level changes.


An Overview of the Mechanisms Against "Candidatus Liberibacter asiaticus": Virulence Targets, Citrus Defenses, and Microbiome.
Citrus Huanglongbing (HLB) or citrus greening, is the most destructive disease for citrus worldwide. It is caused by the psyllid-transmitted, phloem-limited bacteria "Candidatus Liberibacter asiaticus" (CLas). To date, there are still no effective practical strategies for curing citrus HLB. Understanding the mechanisms against CLas can contribute to the development of effective approaches for combatting HLB. However, the unculturable nature of CLas has hindered elucidating mechanisms against CLas. In this review, we summarize the main aspects that contribute to the understanding about the mechanisms against CLas, including (1) CLas virulence targets, focusing on inhibition of virulence genes; (2) activation of citrus host defense genes and metabolites of HLB-tolerant citrus triggered by CLas, and by agents; and (3) we also review the role of citrus microbiome in combatting CLas. Finally, we discuss novel strategies to continue studying mechanisms against CLas and the relationship of above aspects.


Reduction of lumbar spondylolisthesis using a CDI pedicle screw system.
To evaluate reduction methods using two of the several types of Cotrel-Dubousset instrumentation (CDI), 39 patients with low-grade (Meyerding grades I and II [12]) lumbar spondylolisthesis were followed clinically and radiologically for a minimum of 6 months. Our surgical methods were classified into three types as follow: reduction by 2-level assembly using double-threaded screws (type I); reduction by single-level assembly using the double-threaded screws (type II); and reduction by single-level assembly using tulip screws (type III). We found that satisfactory reduction could be achieved by single-level assembly using either the double-threaded or tulip screw without resection of disc material or the posterior leverage method. We found that the tulip screw was superior in obtaining stable reduction. We discuss the mechanism of reducing spondylolisthesis in comparison with that of previously reported methods.


Accidental poisoning with aconite overdose: A case report and resuscitative emergency management in a tertiary level hospital of Bangladesh.
Intoxication with aconite, a common over-the-counter herbal medicine in Asia, can result in ventricular tachycardia and cardiac arrest and requires heart rate monitoring in a critical care setting and aggressive use of antiarrhythmica. Educational efforts in the appropriate use of alternative medicine may help prevent intoxication.


Posttranscriptional control of NLRP3 inflammasome activation in colonic macrophages.
Colonic macrophages (cMPs) are important for intestinal homeostasis as they kill microbes and yet produce regulatory cytokines. Activity of the NLRP3 (nucleotide-binding leucine-rich repeat-containing pyrin receptor 3) inflammasome, a major sensor of stress and microorganisms that results in pro-inflammatory cytokine production and cell death, must be tightly controlled in the intestine. We demonstrate that resident cMPs are hyporesponsive to NLRP3 inflammasome activation owing to a remarkable level of posttranscriptional control of NLRP3 and pro-interleukin-1β (proIL-1β) protein expression, which was also seen for tumor necrosis factor-α and IL-6, but lost during experimental colitis. Resident cMPs rapidly degraded NLRP3 and proIL-1β proteins by the ubiquitin/proteasome system. Finally, blocking IL-10R-signaling in vivo enhanced NLRP3 and proIL-1β protein but not mRNA levels in resident cMPs, implicating a role for IL-10 in environmental conditioning of cMPs. These data are the first to show dramatic posttranscriptional control of inflammatory cytokine production by a relevant tissue-derived macrophage population and proteasomal degradation of proIL-1β and NLRP3 as a mechanism to control inflammasome activation, findings which have broad implications for our understanding of intestinal and systemic inflammatory diseases.


Evaluation of effective treatment depth in skin cancer treatments with electronic brachytherapy.
To evaluate changes in the percent depth dose (PDD) and effective depth of treatment due to force applied by the applicator during treatments of nonmelanoma skin cancer with the Xoft electronic brachytherapy system. To simulate compressible tissue, a 5-mm tissue-equivalent bolus was used. A soft x-ray ion chamber was used for output measurements, which were performed for all Xoft surface applicators with plastic endcaps in place. Output was first measured at 5 mm depth with minimal pressure from the applicator on the bolus and then repeated after applying uniform pressure on the applicator to calculate the change in PDD and effective treatment depth. For the 10-mm cone, a moderate force of 5 N changed the PDD by more than 20%. The effect was also pronounced for the 20-mm cone, while minimal for the 35- and 50-mm cones. Even when only a moderate force was applied, the effective prescription depth changed by several millimeters, on the order of a typical prescription depth. Based on the results of this simulation, excessive pressure applied on the skin by the applicator can drastically alter the PDD and effective treatment depth. The effect is most pronounced for the 10- and 20-mm cones, which tend to be used most frequently. Inappropriate applicator placement may therefore result in significant consequences such as excessive dose to the target, severe skin reaction, permanent discoloration, skin indentation, and poor overall cosmesis upon completion of treatment.


Adolescents' mental health and the Greek family: preventive aspects.
Preventive mental health measures can be properly planned only if the various factors leading to the adolescent's personality structure are extensively investigated. Starting with the specific attitudes of a couple towards genetic counselling, the disadvantages of urbanization and of the dissolution of the traditional extended family are discussed with regard to their effect on the younger members. Data are produced concerning the child-rearing practices of Greek in comparison to American parents and their effect on the adolescent's emotional life. Extreme dependence on the family, pressure for school achievements, lack of sexual education, etc. are characteristic of the stresses a Greek adolescent undergoes. Socio-cultural conditions, like immigration, adoption, etc. are shown to have a different psychological effect on an adolescent in Greece than in America. Specific stresses regarding the adolescent's future, like preparing for university entrance examinations, are discussed and preventive measures are proposed.


PTH1-34 inhibited TNF-α expression and antagonized TNF-α-induced MMP13 expression in MIO mice.
This study aims to investigate the effects and mechanisms of parathyroid hormone [1-34] (PTH1-34) on TNF-α-stimulated mice chondrocytes, as well as cartilage from a meniscus injury induced osteoarthritis (MIO) mice model. The C57BL/6J mice received medial meniscectomy, and then administrated with PTH1-34. The results showed that PTH1-34 administration decreased secondary allodynia and the pain-related transcripts. The IHC, ELISA, Micro-CT imaging and histopathology analysis revealed the significantly improved subchondral plate thickness and bone porosity, the reduced pro-inflammatory cytokines in serum and joint fluid. In vitro, mice chondrocyte was treated with TNF-α or co-cultured with synovial cells. The results showed that TNF-α markedly upregulated the MMP13 expression, and the ERK1/2, NF-κB or PI3K signaling pathway inhibitors could reverse the induction effect of TNF-α on expression of MMP13 in chondrocytes. PTH1-34 alone has no effect on the expression of MMP13 and NF-κB signaling pathways, but the PTH1-34 could reverse the induction effect of TNF-α on MMP13 expression and NF-κB signaling pathway activation in chondrocytes. In addition, PTH1-34 administration inhibited the expression of TNF-α and MMP13, and chondrocyte viability, while the PKA repressor reversed the effect of PTH1-34 in chondrocytes co-cultured with synovial cells. In conclusion, PTH1-34 has an obvious analgesic and anti-inflammatory effect, inhibits the matrix synthesis and alleviates the progression of osteoarthritis. In vitro, PTH1-34 inhibited TNF-α expression and antagonized TNF-α-induced MMP13 expression via the PKA pathway and the NF-κB signaling pathways, respectively.


Purple-grained barley (Hordeum vulgare L.): marker-assisted development of NILs for investigating peculiarities of the anthocyanin biosynthesis regulatory network.
Anthocyanins are plants secondary metabolites important for plant adaptation to severe environments and potentially beneficial to human health. Purple colour of barley grain is caused by the pigments synthesized in pericarp. One or two genes determine the trait. One of them is Ant2 mapped on chromosome 2HL and is known to encode transcription factor (TF) with a bHLH domain. In plants, bHLH regulates anthocyanin biosynthesis together with TF harboring an R2R3-MYB domain. In wheat, the R2R3-MYBs responsible for purple colour of grain pericarp are encoded by the homoallelic series of the Pp-1 genes that were mapped on the short arms of chromosomes 7. In barley, in orthologous positions to wheat's Pp-1, the Ant1 gene determining red colour of leaf sheath has been mapped. In the current study, we tested whether Ant1 has pleiotropic effect not only on leaf sheath colour but also on pericarp pigmentation. А set of near isogenic lines (NILs) carrying different combinations of alleles at the Ant1 and Ant2 loci was created using markers-assisted backcrossing approach. The dominant alleles of both the Ant1 and Ant2 genes are required for anthocyanin accumulation in pericarp. A qRT-PCR analysis of the Ant genes in lemma and pericarp of the NILs revealed that some reciprocal interaction occurs between the genes. Expression of each of the two genes was up-regulated in purple-grained line with dominant alleles at the both loci. The lines carrying dominant allele either in the Ant1 or in the Ant2 locus were characterized by the decreased level of expression of the dominant gene and scant activity of the recessive one. The Ant1 and Ant2 expression was barely detected in uncolored line with recessive alleles at both loci. The anthocyanin biosynthesis structural genes were differently regulated: Chs, Chi, F3h, Dfr were transcribed in all lines independently on allelic state of the Ant1 and Ant2 genes, whereas F3'h and Ans were activated in presence on dominant alleles of the both regulatory genes. The R2R3-MYB-encoding counterpart (Ant1) of the regulatory Ant2 gene was determined for the first time. The dominant alleles of both of them are required for activation of anthocyanin synthesis in barley lemma and pericarp. The R2R3-MYB + bHLH complex activates the synthesis via affecting expression of the F3'h and Ans structural genes. In addition, positive regulatory loop between Ant1 and Ant2 was detected. Earlier the interaction between the anthocyanin biosynthesis regulatory genes has been revealed in dicot plant species only. Our data demonstrated that the regulatory mechanism is considered to be more common for plant kingdom than it has been reported so far.


Valuable Fatty Acids in Bryophytes-Production, Biosynthesis, Analysis and Applications.
Bryophytes (mosses, liverworts and hornworts) often produce high amounts of very long-chain polyunsaturated fatty acids (vl-PUFAs) including arachidonic acid (AA, 20:4 △5,8,11,14) and eicosapentaenoic acid (EPA, 20:5 △5,8,11,14,17). The presence of vl-PUFAs is common for marine organisms such as algae, but rarely found in higher plants. This could indicate that bryophytes did not lose their marine origin completely when they landed into the non-aqueous environment. Vl-PUFA, especially the omega-3 fatty acid EPA, is essential in human diet for its benefits on healthy brain development and inflammation modulation. Recent studies are committed to finding new sources of vl-PUFAs instead of fish and algae oil. In this review, we summarize the fatty acid compositions and contents in the previous studies, as well as the approaches for qualification and quantification. We also conclude different approaches to enhance AA and EPA productions including biotic and abiotic stresses.


Treatment of Aspergillus fumigatus keratitis in rabbits with oral and topical ketoconazole.
Aspergillus fumigatus keratitis was established in rabbits by intrastromal injection of a suspension containing 5,000 spores. After a 48-hour incubation period, the animals were treated with oral and topical ketoconazole alone and in combination with topical natamycin for five days. Colony counts per cornea were obtained at the conclusion of the treatment period. Based on these colony counts, neither oral nor topical ketoconazole was effective despite moderate in vitro sensitivity of the fungus to ketoconazole. Oral and topical ketoconazole used in conjunction with natamycin, however, appeared to augment sterilization of A. fumigatus in this model of fungal keratitis.


Efficacy and pharmacodynamics of linezolid, alone and in combination with rifampicin, in an experimental model of methicillin-resistant Staphylococcus aureus endocarditis.
To evaluate the efficacy of oral linezolid, with or without rifampicin, on valve vegetations and secondary foci of infection compared with vancomycin, in the absence or presence of rifampicin, in experimental endocarditis caused by methicillin-resistant Staphylococcus aureus. Treatment groups were controls (n = 16), linezolid (n = 15), vancomycin (n = 15), linezolid and rifampicin (n = 15), vancomycin and rifampicin (n = 13), linezolid relapse (n = 11) and vancomycin relapse (n = 9). Therapy lasted 5 days in all groups, with survival of animals in the linezolid relapse and vancomycin relapse groups being recorded for an additional 5 days. Blood was drawn to determine the linezolid concentration, and valve vegetations, and kidney, liver, lung and spleen segments were collected for culture. Survival in each individual group was higher than that in the control group; bacterial load in valve vegetations was reduced by all treatment regimens, with linezolid exhibiting bactericidal effects. Bactericidal activity of linezolid was noted in all secondary foci of infection except the lung, where only the combination of rifampicin with linezolid was bactericidal. Orally administered linezolid is effective in limiting bacterial growth in the secondary foci of endocarditis. Co-administration of rifampicin favoured the suppression of bacterial growth in the lung.


Plasminogen activator regulation in osteoblasts: parathyroid hormone inhibition of type-1 plasminogen activator inhibitor and its mRNA.
In order to determine the mechanism by which parathyroid hormone (PTH) stimulates plasminogen activator (PA) activity in rat osteoblasts, we investigated the effect of human PTH(1-34) [hPTH(1-34)] on the synthesis of mRNAs for tissue-type PA (tPA), urokinase-type PA (uPA), and PA inhibitor-1 (PAI-1), and on release of PA activity and PAI-1 protein in both normal rat calvarial osteoblasts and UMR 106-01 osteogenic sarcoma cells. hPTH(1-34) (0.25-25 nM) decreased PAI-1 mRNA and protein, and increased PA activity in both cell types in a dose-dependent manner with ED50 of about 1 nM for both responses. Forskolin and isobutylmethylxanthine also stimulated PA activity and decreased PAI-1 protein and mRNA in both cell types. hPTH(1-34) did not show any consistent effect on tPA and uPA mRNA in calvarial osteoblasts, but a modest (two-fold) increase of both mRNAs was observed in UMR 106-01 cells treated with 25 nM hPTH(1-34). However, when protein synthesis was inhibited with 100 microM cycloheximide, the increase of tPA and uPA mRNA by hPTH(1-34) was enhanced in UMR 106-01 cells and became evident in calvarial osteoblasts. Fibrin autography also revealed that hPTH(1-34) increases tPA and uPA activity, especially after cycloheximide treatment in UMR 106-01 cells. These results strongly suggest that PTH increases PA activity predominantly by decreasing PAI-1 protein production through a cyclic adenosine monophosphate (cAMP)-dependent mechanism in rat osteoblasts. The reduction of PAI-1 protein by PTH results in enhanced action of both tPA and uPA, and would contribute to the specific roles of these PAs in bone.


CSF2-STAT5 Signaling in TAMs Contributes to CSF1R Inhibition Resistance.
CSF1R inhibition combined with STAT5 blockade normalized TAM phenotype and sustained tumor control.


Heparin blocks the adhesion of E. coli O157:H7 to human colonic epithelial cells.
Adhesion of Shiga toxin-producing Enterohemorrhagic Escherichia coli (EHEC) O157:H7 to human colonic epithelium is a critical step for infection by this type of bacteria. Here, we demonstrate that adherence of EHEC O157:H7 to cultured human colonic T84 epithelial monolayers can be blocked by heparin and heparan sulfate in a dose-dependent fashion. In doing this, heparin and heparan sulfate also prevent dysfunction of the T84 barrier and disorganization of epithelial tight junction protein ZO-1 caused by EHEC O157:H7. This inhibition by heparin and heparan sulfate seems to result from a block in the binding interactions of bacteria intimin with epithelial beta(1) integrins. This study provides evidence, for the first time, that heparin and heparan sulfate can serve as novel effective blockers in preventing EHEC O157:H7 infection.


Can a school based programme in a natural environment reduce BMI in overweight adolescents?
Current levels of obesity amongst adolescents may be largely attributed to changes in environmental exposures that place vulnerable youth at risk, yet few studies have incorporated environmental approaches to normalising Body Mass Index (BMI). Our hypothesis is that a live-in school based programme in a natural environment can reduce the BMI of overweight children. The pilot study therefore explores the effects of such a programme on the BMI of adolescents in rural Victoria, Australia. Year 9 students (15 year olds, N = 1021) at a rural school with a physically demanding, 10-month, live-in outdoor programme had their BMIs measured at the beginning and end of the programme. Their observed BMI at the end of the programme was compared to expected BMI (based on adjustment of their initial BMI to account for normal growth using international standards). Participation in the programme reduced the BMI of boys who were in the normal to obese range (χ(2) = 8.57, p = 0.014), but not in girls. For the overweight and obese boys BMI decreased by up to 2.5 kg/m(2). These results suggests that school based environmental interventions may be effective in reducing obesity in adolescents, supporting our hypothesis. Our study is limited by its opportunistic observational nature, but it nevertheless suggests that such a live-in school programme in a natural environment may provide a valuable addition to the list of interventions available to combat the obesity epidemic. Although the programme reduced BMI in boys, the equivocal data for girls means that even an intensive programme such as this struggles to achieve a significant change in BMI across all obese adolescents. Our study nevertheless supports the need for further investigation of the possible contribution of school based programmes in natural environments to interventions to fight the obesity epidemic--because there is no magic bullet.


Feasibility, acceptability and potential helpfulness of the PROACTIVE intervention in Flanders, Belgium: A survey study.
This study aimed to explore the feasibility of a Flemish adaptation of the New York University Caregiver Intervention (i.e., PROACTIVE intervention) modifying the recruitment and intervention content for informal caregivers of people with early cognitive decline, and across different subgroups. A feasibility study is necessary in order to reduce research waste for intervention adaptation and evaluation. Researchers constructed, tested, and sent out a survey consisting of 43 questions on the following topics: awareness of symptoms of early cognitive decline, levels of cognitive performance using the updated Cognitive Performance Scale (CPS2), acceptability, and potential helpfulness of the intervention, and sociodemographic characteristics. Quantitative data were analyzed using descriptive statistics and logistic regression with SAS 9.4©. Qualitative data were analyzed using an inductive content analysis. A total of 463 informal caregivers completed the survey (mean age 58.8 ± 11.8, 83.6% female). Among them, 230 respondents who cared for people with cognitive decline indicated they would probably or certainly participate in the study. Identified factors influencing the recruitment were cognition, co-habitation, education, and employment status. Over half of the target caregivers indicated almost all services from the intervention could satisfy their needs. A majority perceived the PROACTIVE intervention would be helpful (69.4%), especially the CPS2 = 3 (76.1%) and CPS2 = 4 (74.1%) subgroups. The recruitment of target participants for a subsequent RCT evaluation study is feasible, and identified associated factors should be considered during the recruitment process. The PROACTIVE intervention and core components except 'peer-group participation' were perceived as helpful by most caregivers. The CPS2 = 3-4 subgroups were most accepting of the intervention and were most likely to benefit from the intervention.


Geometry in visual space-some method-dependent (arti)facts.
The measure of scalar curvature K varies with the method used to determine it. Overconstancy is found only with simultaneous comparison, nearly perfect constancy results from successive judgement, while absolute judgement produces underconstancy.


Survival among Breast Cancer Patients: Comparison of the U.S. Military Health System with the Surveillance, Epidemiology and End Results Program.
Accessibility to health care is important to cancer survival. The U.S. military health system (MHS) provides universal health care access. However, whether the universal care has been translated into improved cancer survival is unknown. We compared survival of patients with breast cancer in the MHS with that in the U.S. general population and assessed the differences in cancer stage at diagnosis and treatment receipt between the two populations. The MHS patients (n = 31,548) were identified from the Department of Defense's (DoD) Automated Central Tumor Registry (ACTUR). Patients in the U.S. general population (n = 63,096) were identified from the Surveillance, Epidemiology, and End Results (SEER) program. The two populations were matched on age, race, and diagnosis year. Multivariable Cox regression hazard modeling was used to estimate hazard ratios (HRs) comparing ACTUR with SEER. Multivariable logistic regression was used to estimate odds ratios (ORs) comparing stage and treatment receipt. ACTUR patients exhibited a 24% lower overall mortality than the SEER patients (HR = 0.76, 95% CI, 0.71-0.80). They were less likely to present with later stage compared to the SEER patients (OR = 0.61, 95% CI, 0.55-0.67 for stage IV tumors). The ACTUR patients with stages I-III tumors were more likely to receive surgery (OR = 1.35, 95% CI, 1.20-1.52) but less likely to receive radiation (OR = 0.91, 95% CI, 0.88-0.94). The survival advantage of ACTUR patients remained regardless of surgery or radiation receipt. Breast cancer patients with universal health care access had improved survival compared to patients in the general population.


Prevalence of type III secretion system in effective biocontrol pseudomonads.
Functional type III secretion system (T3SS) genes are needed for effective biocontrol of Pythium damping-off of cucumber by Pseudomonas fluorescens KD, but whether biocontrol Pseudomonas strains with T3SS genes display overall a higher plant-protecting activity is unknown. The assessment of 198 biocontrol fluorescent pseudomonads originating from 60 soils worldwide indicated that 32% harbour the ATPase-encoding T3SS gene hrcN, which was most often found in tomato isolates. The hrcN(+) biocontrol strains (and especially those also producing 2,4-diacetylphloroglucinol and displaying 1-aminocyclopropane-1-carboxylate deaminase activity) displayed higher plant-protecting ability in comparison with hrcN(-) biocontrol strains, both in the Pythium/cucumber and Fusarium/cucumber pathosystems.


Chest pain: relationship of psychiatric illness to coronary arteriographic results.
Seventy-four patients with chest pain and no prior history of organic heart disease were interviewed with a structured psychiatric interview immediately after coronary arteriography. The majority of patients with both negative and positive coronary angiographies had undergone previous exercise tolerance tests, but the patients with angiographic coronary artery disease were significantly more likely to have had positive results on a treadmill test. Patients with chest pain and negative coronary arteriograms were significantly younger; more likely to be female; more apt to have a higher number of autonomic symptoms (tachycardia, dyspnea, dizziness, and paresthesias) associated with chest pain, and more likely to describe atypical chest pain. Patients with chest pain and normal coronary arteriographic results also had significantly higher psychologic scores on indices of anxiety and depression and were significantly more likely to meet criteria of the Diagnostic and Statistical Manual of Mental Disorders, third edition, for panic disorder (43 percent versus 6.5 percent), major depression (36 percent versus 4 percent), and two or more phobias (36 percent versus 15 percent) than were patients with chest pain and a coronary arteriography study demonstrating coronary artery stenosis.


Melatonin Pathway and Atenolol-Related Glucose Dysregulation: Is There a Correlation?
Lower melatonin level, melatonin receptor gene variations, and atenolol treatment are associated with glucose dysregulation. We investigated whether atenolol-related glucose and melatonin changes are correlated, and whether single nucleotide polymorphisms (SNPs) in melatonin candidate genes contribute to interindividual variation in glucose change. Hypertensive Caucasians (n = 232) from the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) study treated with atenolol for 9 weeks were studied. Urinary 6-sulfatoxymelatonin (aMT6s) was measured pre- and posttreatment and normalized to urinary creatinine. Pharmacogenetic effects on glucose change of 160 SNPs in 16 melatonin candidate genes were assessed with multiple linear regression. Atenolol was associated with increased glucose (1.8 ± 10.1mg/dl, P = 0.02) and decreased aMT6s (-4.5 ± 10.1 ng/mg, P < 0.0001). However, the aMT6s change was not correlated with post-atenolol glucose change. SNP rs11649514 in PRKCB was associated with glucose change (P = 1.0×10(-4)). PRKCB is involved in the melatonin-insulin regulatory pathway, and may be important in mediating clinically meaningful atenolol-related hyperglycemia.


Anti-lipolytic action of prazosin in hamster fat cells.
Using isolated white fat cells of the hamster, we studied the possible inhibitory effects on lipolysis of the preferentially selective alpha-1-adrenoceptor blocking and anti-hypertensive agent prazosin. Parallel studies were undertaken with the preferentially alpha-2-adrenoceptor blocking agent yohimbine. Neither of the compounds had any significant effects on basal (non-stimulated) lipolysis. When lipolysis was stimulated by noradrenaline or isoprenaline, however, prazosin showed significant anti-lipolytic effects from a concentration of 10(-6) M. Lipolysis stimulated by methylisobutylxanthine was antagonized by prazosin only at a concentration of 10(-4) M, and dibutyrylcyclic adenosine 3'5' monophosphate-stimulated lipolysis was not inhibited at all. It is suggested that prazosin inhibits lipolysis by preventing adenyl cyclase activation by an indirect mechanism not identifiable with an alpha-2-adrenergic function but associated possibly with the formation of a local inhibitory mediator. These observations are compatible with a reduction of the outflow of free fatty acids from adipose stores in patients undergoing prazosin therapy and thus a breaking of the "vicious circle" leading to elevated plasma lipoproteins and may explain, in part at least, the reduction in plasma lipid levels observed during prazosin treatment in man.


Production efficiency and properties of bacterial cellulose membranes in a novel grape pomace hydrolysate by Komagataeibacter melomenusus AV436T and Komagataeibacter xylinus LMG 1518.
The microbial production of cellulose using different bacterial species has been extensively examined for various industrial applications. However, the cost-effectiveness of all these biotechnological processes is strongly related to the culture medium for bacterial cellulose (BC) production. Herein, we examined a simple and modified procedure for preparing grape pomace (GP) hydrolysate, without enzymatic treatment, as a sole growth medium for BC production by acetic acid bacteria (AAB). The central composite design (CCD) was used to optimise the GP hydrolysate preparation toward the highest reducing sugar contents (10.4 g/L) and minimal phenolic contents (4.8 g/L). The experimental screening of 4 differently prepared hydrolysates and 20 AAB strains identified the recently described species Komagataeibacter melomenusus AV436T as the most efficient BC producer (up to 1.24 g/L dry BC membrane), followed by Komagataeibacter xylinus LMG 1518 (up to 0.98 g/L dry BC membrane). The membranes were synthesized in only 4 days of bacteria culturing, 1 st day with shaking, followed by 3 days of static incubation. The produced BC membranes in GP-hydrolysates showed, in comparison to the membranes made in a complex RAE medium 34 % reduction of crystallinity index with the presence of diverse cellulose allomorphs, presence of GP-related components within the BC network responsible for the increase of hydrophobicity, the reduction of thermal stability and 48.75 %, 13.6 % and 43 % lower tensile strength, tensile modulus, and elongation, respectively. Here presented study is the first report on utilising a GP-hydrolysate without enzymatic treatment as a sole culture medium for efficient BC production by AAB, with recently described species Komagataeibacter melomenusus AV436T as the most efficient producer in this type of food-waste material. The scale-up protocol of the scheme presented here will be needed for the cost-optimisation of BC production at the industrial levels.


A pH-Dependent rhodamine fluorophore with antiproliferative activity of bladder cancer in Vitro/Vivo and apoptosis mechanism.
Herein, 26 rhodamine fluorophores were synthesized from readily available Rh-6G and relative amines at room temperature with good selectivity, functional groups compatibility and high yields. We found that one of them 3f showed pH-dependent anticancer bioactivity, with cell viability of 68.4% under pH 6.5 and 83.2% under pH 7.5, LDH fold change of 42.8% under pH 6.5 and 26.4% under pH 7.5 in 22.35 μM in human bladder cancer cell line EJ. Besides, 3f showed anticancer bioactivity in vivo towards human bladder cancer, by triggering apoptosis through mitochondrial pathway.


[Fatal multiple pterygium syndrome and nuchal hygroma].
A turkish family with three sibs (including twins) affected by the lethal multiple syndrome is reported.


Positive cooperative action of follicle-stimulating hormone on binding of luteinizing hormone to testicular receptors from the bullfrog (Rana catesbeiana).
We found that the bullfrog testis has specific gonadotropin-binding sites of only a single type which have the same affinity for both follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the bullfrog. The affinity (the equilibrium constant of dissociation or Kd) and capacity (the number of binding sites) of the binding sites for FSH were 0.49 nM and 0.27 fmol/mg fresh tissue, respectively, and those for LH were 0.53 nM and 0.23 fmol/mg fresh tissue, respectively, when these parameters were determined independently. Specific binding of labeled FSH was completely displaced by both FSH and LH, and their competition curves were identical. However, when labeled LH was used, the slope of the curve for competition by FSH was much gentler than that of the curve for competition by LH. A large amount of FSH (about 5 micrograms/ml) was required to replace labeled LH and to reduce the binding of LH to the nonspecific binding level. To explain this result, we assumed the model of nonlinear positive cooperativity by heterologous hormones, in which the affinity for LH of the binding sites is increased in proportion to the number of sites occupied by FSH, raised to the cth power, where c is a constant. When the observed equilibrium parameters were employed and appropriate values for c and for Kf (the Kd for completely occupied binding sites) were chosen as 1.45 and 0.00045 nM, respectively, the theoretical curve for competition by FSH against labeled LH coincided almost exactly with the observed curve. The positive cooperative action of FSH on the binding of LH was also shown by association experiments, but not by dissociation experiments. The positive cooperative action of a heterologous hormone may be a device developed in anurans to overcome the problem that one of the two gonadotropins competitively inhibits the action of the other when both gonadotropins are secreted simultaneously.


Preliminary evaluation of a coping skills training program for those with a pathological-gambling partner.
Individuals living with a pathological-gambling partner can experience significant psychological distress. In this report, we conduct a preliminary evaluation of a coping skills training program (CST) for this population. Twenty-three individuals experiencing stress from living with a pathological-gambling partner who was not in treatment were randomly assigned to either CST or a delayed treatment control (DTC) condition. CST consisted of ten, weekly individual sessions to teach more effective coping skills. At the end of the treatment/delay period, CST participants, relative to those in DTC, showed a large improvement in coping skillfulness that appeared to mediate a corresponding large significant reduction in depression and anxiety relative to DTC. Partner gambling during the period decreased in both conditions but did not differ between them, nor did partner help-seeking differ. CST shows promise as an effective treatment for individuals distressed as a result of a partner's gambling problem. Larger, longer-term evaluations of the intervention, and comparison with alternate treatment models are needed.


Distinction of hemangiomas from hepatic tumors with delayed enhancement by incremental dynamic CT.
To analyze the patterns of contrast enhancement and to evaluate clinical utility, we performed table incremental dynamic CT in 21 patients with 30 hepatic hemangiomas and in 12 patients with 26 malignant neoplasms, which showed delayed enhancement. On incremental CT, dense, spotty peripheral enhancement was present in 23 of the 30 (77%) hemangiomas. In contrast, a circumferential bead- or band-like peripheral enhancement was seen in 19 of 26 (73%) malignant neoplasms. The findings were characteristic. We conclude that incremental CT is useful in the differential diagnosis of hepatic hemangioma in routine examination.


The initiative for pediatric palliative care: an interdisciplinary educational approach for healthcare professionals.
There is growing empirical evidence that the U.S. healthcare system fails to meet the needs of children with life-threatening conditions and their families. The confluence of several recent developments has created a critical window of opportunity for improving clinical practice and institutional effectiveness in pediatric palliative care. This article presents an innovative, comprehensive approach to pediatric palliative care education that was developed by the Initiative for Pediatric Palliative Care, a consortium of seven academic children's hospitals, Education Development Center, the National Association of Children's Hospitals and Related Institutions, the New York Academy of Medicine, the Society of Pediatric Nursing, and the Association of Medical School Pediatric Department Chairs. The approach is based on needs assessment research with clinicians and parents and reflects a commitment to culturally respectful, family-centered care of children with life-threatening conditions. The pedagogy combines principles of adult education, includes families as teachers, and integrates affective and cognitive dimensions to enhance learning.


Calcium entry blockers: antihypertensive and natriuretic effects in experimental animals.
Hypotensive and natriuretic effects of calcium entry blockers were studied in spontaneously hypertensive rats (SHRs) and normotensive Wistar Kyoto rats (WKYs). In SHRs, the hypotensive action of diltiazem was enhanced, while that of hydralazine was not different from its action in WKYs. Diltiazem, unlike hydralazine and nifedipine, did not cause reflex tachycardia in rats. Diltiazem and nifedipine caused an increase in urine volume and sodium excretion. The natriuretic potency of diltiazem was the same in both SHRs and WKYs and was not affected by pretreatment with indomethacin. Diltiazem increased plasma renin activity but had no influence on plasma aldosterone concentration. Hydralazine increased both plasma renin activity and plasma aldosterone concentration and decreased sodium excretion. In anesthetized dogs, diltiazem increased sodium excretion, glomerular filtration rate and renal blood flow. Diltiazem may have a direct effect on tubular sodium reabsorption. This assumption was supported by a study with short-circuit current of the isolated bullfrog bladder. It is likely that diltiazem's effect of increasing urine volume and sodium excretion is due mainly to changes in renal hemodynamics and partly to direct action on renal tubules. Diltiazem opposed angiotensin II-induced responses, such as renal vasoconstriction and reduction of glomerular filtration rate. Under this condition, a marked natriuretic effect was observed with both intravenous and intraarterial administration of diltiazem. The ability to increase urinary excretion of sodium is a desirable characteristic for an antihypertensive agent. Calcium entry blockers have this ability and are therefore able to act without causing sodium and water retention.


How to Avoid Life-Threatening Complications Associated with Implant Surgery.
Life-threatening complications of dental implant surgery are rare, but include hematoma/hemorrhage of the floor of the mouth, aspiration, and ingestion. Prevention of lethal hemorrhagic complications stem from knowledge of anatomic structures and precise surgical planning. Prevention of aspiration and ingestion can be improved by simple techniques while understanding clinical settings and factors that put patients at higher risk. In the event of these potential lethal situations, early recognition of signs and symptoms along with immediate action followed by transfer to an emergency department is often necessary.


Adaptation to acetaminophen exposure elicits major changes in expression and distribution of the hepatic proteome.
Acetaminophen overdose is the leading cause of acute liver failure. One dose of 10-15 g causes severe liver damage in humans, whereas repeated exposure to acetaminophen in humans and animal models results in autoprotection. Insight of this process is limited to select proteins implicated in acetaminophen toxicity and cellular defence. Here we investigate hepatic adaptation to acetaminophen toxicity from a whole proteome perspective, using quantitative mass spectrometry. In a rat model, we show the response to acetaminophen involves the expression of 30% of all proteins detected in the liver. Genetic ablation of a master regulator of cellular defence, NFE2L2, has little effect, suggesting redundancy in the regulation of adaptation. We show that adaptation to acetaminophen has a spatial component, involving a shift in regionalisation of CYP2E1, which may prevent toxicity thresholds being reached. These data reveal unexpected complexity and dynamic behaviour in the biological response to drug-induced liver injury.


Effects of l- and d-propranolol on the ischemic myocardial metabolism of the isolated guniea pig heart, as studied by 31P-NMR.
Using 31P nuclear magnetic resonance (NMR) spectroscopy (acquisition time of 3 min), we studied the effects of l- and d-propranolol on the ischemic derangement of myocardial energy metabolism in the isolated perfused guinea pig heart. The myocardial pH and concentration of high-energy phosphate were used as measures of the energy metabolism. Cardiac pH progressively declined during ischemia from 7.41 +/- 0.04 to 7.13 +/- 0.05, 6.91 +/- 0.04, 6.74 +/- 0.04, and 6.61 +/- 0.04 (before ischemia and 3, 6, 9, and 12 min after ischemia, respectively). After 3 min of reperfusion, pH rapidly returned to 7.42 +/- 0.04. Creatine phosphate (CP) and adenosine triphosphate (ATP) contents were reduced, while inorganic phosphate (Pi) contents were increased during ischemia. Whereas CP and Pi contents were restored to the normal values after reperfusion, the recovery of ATP contents was poor. Both l- and d-propranolol (10(-6) M) significantly suppressed the fall of the myocardial pH. Changes in the high-energy phosphate contents were also attenuated by l- and d-propranolol. These results suggest that not only l-propranolol, but also d-propranolol can produce beneficial effects on the ischemic derangements of myocardial energy metabolism.