Enzymatic Synthesis of Amino Acids Endcapped Polycaprolactone: A Green Route Towards Functional Polyesters.
ε-caprolactone (CL) has been enzymatically polymerized using α-amino acids based on sulfur (methionine and cysteine) as (co-)initiators and immobilized lipase B of Candida antarctica (CALB) as biocatalyst. In-depth characterizations allowed determining the corresponding involved mechanisms and the polymers thermal properties. Two synthetic strategies were tested, a first one with direct polymerization of CL with the native amino acids and a second one involving the use of an amino acid with protected functional groups. The first route showed that mainly polycaprolactone (PCL) homopolymer could be obtained and highlighted the lack of reactivity of the unmodified amino acids due to poor solubility and affinity with the lipase active site. The second strategy based on protected cysteine showed higher monomer conversion, with the amino acids acting as (co-)initiators, but their insertion along the PCL chains remained limited to chain endcapping. These results thus showed the possibility to synthesize enzymatically polycaprolactone-based chains bearing amino acids units. Such cysteine endcapped PCL materials could then find application in the biomedical field. Indeed, subsequent functionalization of these polyesters with drugs or bioactive molecules can be obtained, by derivatization of the amino acids, after removal of the protecting group.


Regulation and Functions of α6-Integrin (CD49f) in Cancer Biology.
Over the past decades, our knowledge of integrins has evolved from being understood as simple cell surface adhesion molecules to receptors that have a complex range of intracellular and extracellular functions, such as delivering chemical and mechanical signals to cells. Consequently, they actively control cellular proliferation, differentiation, and apoptosis. Dysregulation of integrin signaling is a major factor in the development and progression of many tumors. Many reviews have covered the broader integrin family in molecular and cellular studies and its roles in diseases. Nevertheless, further understanding of the mechanisms specific to an individual subunit of different heterodimers is more useful. Thus, we describe the current understanding of and exploratory investigations on the α6-integrin subunit (CD49f, VLA6; encoded by the gene itga6) in normal and cancer cells. The roles of ITGA6 in cell adhesion, stemness, metastasis, angiogenesis, and drug resistance, and as a diagnosis biomarker, are discussed. The role of ITGA6 differs based on several features, such as cell background, cancer type, and post-transcriptional alterations. In addition, exosomal ITGA6 also implies metastatic organotropism. The importance of ITGA6 in the progression of a number of cancers, including hematological malignancies, suggests its potential usage as a novel prognostic or diagnostic marker and useful therapeutic target for better clinical outcomes.


Ultrasonographic stress testing of ulnar collateral ligament injuries of the thumb.
We compared ultrasonographic stress test evaluation to clinical examination of ulnar collateral ligament injuries to the thumb. The results of the sonographic and clinical examinations were compared to either operative findings or clinical follow-up results if conservative treatment was elected. Of 25 patients, the clinical grade injury was identified correctly in 25 with ultrasonography compared to 24 with clinical examination. Of the grade III tears, ultrasonography missed two patients with Stener tears and physical examination misidentified or missed four patients with Stener tears. These results confirm the experience of others that ultrasonography is a useful method to evaluate injury to the ulnar collateral ligament of the thumb.


Comparison of Homo-Polyimide Films Derived from Two Isomeric Bis-Benzimidazole Diamines.
Heteroaromatic polyimides (PIs) containing benzimidazole have attracted tremendous attention due to their positive impact on the properties of PIs. Some research on PIs containing 4,4'-[5,5'-bi-1H-benzimidazole]-2,2'-diylbis-benzenamine (4-AB) has been reported. However, reports are lacking on homo-polyimides (homo-PIs) containing 3,3'-[5,5'-bi-1H-benzimidazole]-2,2'-diylbis-benzenamine (3-AB), which is one of the isomers of 4-AB. In this paper, the influence of amino groups' positions on the performance of homo-PIs was investigated. It was found that the net charge of the amine N group in 4-AB was lower than that of 3-AB, resulting in higher reactivity of 4-AB. Consequently, PIs containing 4-AB displayed better mechanical performance. Molecular simulation confirmed that 3-AB and its corresponding PI chain exhibited distorted conformation, leading to the PI films containing 3-AB having a lighter color. In addition, the 3-AB structure was calculated to have higher rotational energy compared to 4-AB, resulting in a higher glass transition temperature (Tg) in PIs prepared from 3-AB. On the other hand, PIs containing 4-AB exhibited a higher level of molecular linearity, leading to a lower coefficient of thermal expansion (CTE) compared to PIs prepared from 3-AB. Furthermore, all PIs showed higher thermal stability with a 5% weight loss temperature above 530 °C and Tg higher than 400 °C.


[Oxidized LDL, clinical aspects and measurement methods].
It is well recognized that oxidative modification of low-density lipoprotein(LDL) accelerates atherogenesis of the arterial vascular wall. Each of lipid peroxidation products, surface charge, or spectrophotometric patterns is applicable to the evaluation of in vitro oxidation. The lag time may contribute to the evaluation of effect of the lipid lowering and antioxidant drugs. ELISA using monoclonal antibody has the potential for clinical use. However, the applicability is not yet established, because of the different kinds of antibody used.


Single-cell variability of growth interactions within a two-species bacterial community.
Cell-cell interaction networks have been examined in many high diversity microbial communities using macroscale approaches. Microscale studies of multispecies communities are lacking and it remains unclear how macroscale trends scale down to small groups of cells. Experimental approaches using microfluidic devices have revealed heterogeneity in the behavior of single cells, however, this analysis has not been extended towards the variability of cell-cell interactions. Using a microwell device, we analyzed cell growth within hundreds of replicate microbial communities consisting of two species and small population sizes. The wells of the devices were inoculated with a coculture of Escherichia coli and Enterobacter cloacae. Each species expressed a unique fluorescent protein enabling simultaneously tracking of cell number for each species over time. Growth dynamics within the device were consistent with bulk measurements. The device enabled monitoring of replicate, isolated coculture populations at high magnification, revealing both the growth interaction between the two species and the variability of such cell-cell interactions within small groups of cells. The device enables new experimental measurements of the heterogeneity of interactions within small, multispecies populations of bacteria.


AFFINE-CORRECTED PARADISE: FREE-BREATHING PATIENT-ADAPTIVE CARDIAC MRI WITH SENSITIVITY ENCODING.
We propose a real-time cardiac imaging method with parallel MRI that allows for free breathing during imaging and does not require cardiac or respiratory gating. The method is based on the recently proposed PARADISE (Patient-Adaptive Reconstruction and Acquisition Dynamic Imaging with Sensitivity Encoding) scheme. The new acquisition method adapts the PARADISE k-t space sampling pattern according to an affine model of the respiratory motion. The reconstruction scheme involves multi-channel time-sequential imaging with time-varying channels. All model parameters are adapted to the imaged patient as part of the experiment and drive both data acquisition and cine reconstruction. Simulated cardiac MRI experiments using the realistic NCAT phantom show high quality cine reconstructions and robustness to modeling inaccuracies.


Independent prognostic role of human papillomavirus genotype in cervical cancer.
Although the correlation of HPV genotype with cervical precursor lesions and invasive cancer has been confirmed, the role of HPV genotype in cervical cancer prognosis is less conclusive. This study aims to systematically investigate the independent prognostic role of HPV genotype in cervical cancer. A total of 306 eligible patients provided cervical cell specimens for HPV genotyping before therapy and had a median follow-up time of 54 months after diagnosis. Survival times were measured from the date of diagnosis to the date of cervical cancer-related death (overall survival, OS) and from the date of diagnosis to the date of recurrence or metastasis (disease free survival, DFS). Log-rank tests and Cox proportional hazard models were performed to evaluate the association between HPV genotype and survival times. A total of 12 types of high-risk HPV were detected and the leading ten types belong to two species: alpha-9 and alpha-7. HPV16 and 18 were the two most common types, with the prevalence of 60.8% and 8.8%, respectively. In the univariate analysis, HPV16-positive cases were associated with better OS (P = 0.037) and HPV16-related species alpha-9 predicted better OS and DFS (both P < 0.01). After adjusting for age, FIGO stage, and therapy, HPV16 showed a hazard ratio (HR) of 0.36 (95% CI: 0.18, 0.74; P = 0.005) for OS, and alpha-9 resulted in a HR of 0.17 (95% CI: 0.08, 0.37; P < 0.001) for OS and 0.32 (95% CI: 0.17, 0.59; P < 0.001) for DFS. HPV genotype poses differential prognoses for cervical cancer patients. The presence of HPV16 and its related species alpha-9 indicates an improved survival.


Broadband coherent anti-Stokes Raman scattering light generation in BBO crystal by using two crossing femtosecond laser pulses.
As broad as 12000 cm(-1) coherent anti-Stokes Raman scattering (CARS) light from ultraviolet to infrared was generated in a BBO crystal by using two crossing femtosecond laser pulses with 30% conversion efficiency. More than fifteenth-order anti-Stokes and second-order Stokes Raman sidebands were observed with nice Gaussian spatial mode. The effect of the crossing angle between two input beams on the spectrum and emitting angle of the Raman sidebands was studied in detail. Calculation shows that the phase-matching condition determines the frequencies and angles of the sidebands.


[Metabolische Ursachen von Dyspnoe].
Endocrinological or metabolic disorders often affect a wide variety of functions of the organism. This can also include an impairment of respiratory function. Diabetic ketoacidosis as a result of insulin deficiency is a typical metabolic acidosis, which the body tries to compensate by an increased exhalation of carbon dioxide. This leads to the classic picture of "Kussmaul" breathing. Due to the increased use of SGLT2 inhibitors, which can reduce the otherwise typical hyperglycemia and thus complicate diagnosis, the occurrence of diabetic ketoacidosis has remained an important differential diagnosis in recent years. Pathologies of the thyroid gland can lead to dyspnea not only by morphological changes, for example in the case of goiter (compression). Functional disorders must also be considered here. Both hypo- and hyperthyroidism affect the cardiovascular system in different ways and may ultimately lead to the clinical picture of dyspnea. If the corresponding entities are thought of, the laboratory diagnosis of the aforementioned metabolic/endocrinological disorders is then basically straightforward. Accordingly, knowledge of these disorders as a differential diagnosis of tachy- and dyspnea is important.


Electrotaxis-on-Chip to Quantify Neutrophil Migration Towards Electrochemical Gradients.
Electric fields are generated in vivo in a variety of physiologic and pathologic settings, including wound healing and immune response to injuries to epithelial barriers (e.g. lung pneumocytes). Immune cells are known to migrate towards both chemical (chemotaxis), physical (mechanotaxis) and electric stimuli (electrotaxis). Electrotaxis is the guided migration of cells along electric fields, and has previously been reported in T-cells and cancer cells. However, there remains a need for engineering tools with high spatial and temporal resolution to quantify EF guided migration. Here we report the development of an electrotaxis-on-chip (ETOC) platform that enables the quantification of dHL-60 cell, a model neutrophil-like cell line, migration toward both electrical and chemoattractant gradients. Neutrophils are the most abundant white blood cells and set the stage for the magnitude of the immune response. Therefore, developing engineering tools to direct neutrophil migration patterns has applications in both infectious disease and inflammatory disorders. The ETOC developed in this study has embedded electrodes and four migration zones connected to a central cell-loading chamber with migration channels [10 µm X 10 µm]. This device enables both parallel and competing chemoattractant and electric fields. We use our novel ETOC platform to investigate dHL-60 cell migration in three biologically relevant conditions: 1) in a DC electric field; 2) parallel chemical gradient and electric fields; and 3) perpendicular chemical gradient and electric field. In this study we used differentiated leukemia cancer cells (dHL60 cells), an accepted model for human peripheral blood neutrophils. We first quantified effects of electric field intensities (0.4V/cm-1V/cm) on dHL-60 cell electrotaxis. Our results show optimal migration at 0.6 V/cm. In the second scenario, we tested whether it was possible to increase dHL-60 cell migration to a bacterial signal [N-formylated peptides (fMLP)] by adding a parallel electric field. Our results show that there was significant increase (6-fold increase) in dHL60 migration toward fMLP and cathode of DC electric field (0.6V/cm, n=4, p-value<0.005) vs. fMLP alone. Finally, we evaluated whether we could decrease or re-direct dHL-60 cell migration away from an inflammatory signal [leukotriene B4 (LTB4)]. The perpendicular electric field significantly decreased migration (2.9-fold decrease) of dHL60s toward LTB4vs. LTB4 alone. Our microfluidic device enabled us to quantify single-cell electrotaxis velocity (7.9 µm/min ± 3.6). The magnitude and direction of the electric field can be more precisely and quickly changed than most other guidance cues such as chemical cues in clinical investigation. A better understanding of EF guided cell migration will enable the development of new EF-based treatments to precisely direct immune cell migration for wound care, infection, and other inflammatory disorders.


Perioperative nursing in public university hospitals: an ethnography.
In recent years, perioperative nursing has received ongoing attention as part of an interprofessional collaboration. Perioperative nursing is constantly faced with new challenges and opportunities that necessitate continual updates of nursing knowledge and technical skills. In light of the longstanding relationship between nursing and technology, it is interesting that few studies with this focus have been performed. Therefore, our research question was: What is the content of perioperative nursing and how do nurses facilitate the interaction between nursing care and technology in highly specialized operating rooms in public university hospitals? An ethnography involving participant observations and interviews was conducted during a 9-month study period. The participants comprised 24 nurses from 9 different operating wards at 2 university hospitals in different regions of Denmark. Patients were addressed as either human beings or objects. Likewise, the participants' technical skills were observed and described as either technical flair or a lack of technical skills/technophobia. The different ways in which the technical skills were handled and the different ways in which the patients were viewed contributed to the development of three levels of interaction between technology and nursing care: the interaction, declining interaction, and failing interaction levels. Nursing practice at the interaction level is characterized by flexibility and excellence, while practice at the declining interaction level is characterized by inflexibility and rigidity. Nursing practice at the failing interaction level is characterized by staff members working in isolation with limited collaboration with other staff members in operating rooms. Considering that the declining and failing interaction levels are characterized by inflexibility, rigidity, and isolation in nursing practice, nurses at these two levels must develop and improve their qualifications to reach a level of flexible, excellent interaction. Nurse leaders must therefore refocus their skills on proficiency in perioperative nursing.


Efficacy of antiarrhythmic drug therapy in preventing recurrence of atrial fibrillation and long-term cardiovascular prognosis in patients with asymptomatic paroxysmal atrial fibrillation.
We evaluated the efficacy of antiarrhythmic drug therapy (AAD) and long-term cardiovascular prognosis in patients with asymptomatic paroxysmal atrial fibrillation (AF). This retrospective study included 334 patients (229 men and 105 women, mean age, 69 +/- 11 years, mean follow-up, 60 +/- 11 months) who were divided into two groups; patients with symptomatic AF (group I) and those with asymptomatic AF (group II) on the basis of subjective symptoms. (1) Actuarial rates of patients without AF recurrence, those with AF recurrence and with electrical/pharmacological cardioversion to restore sinus rhythm, and those with conversion to permanent AF despite AAD were 40%, 41%, and 19%, respectively, in group I, and 22%, 24%, and 54%, respectively, in group II at the end of the follow-up period. At 60 months, the percentage of patients with conversion to the permanent form of AF was significantly greater in group II than in group I (P < 0.05, group I versus group II). (2) Survival rates free from symptomatic thromboembolism at 36, 60, and 120 months were 96%, 93%, and 88%, in group I, and 82%, 76%, and 71%, respectively, in group II (P < 0.05, group I versus group II). In patients not undergoing anticoagulant therapy, the annual rate of symptomatic thromboembolism was significantly greater in group II (5.3%) than in group I (2.3%) (P < 0.05), while in patients undergoing anticoagulant therapy there was no significant difference in the annual rate of symptomatic thromboembolism between group I (0.9%) and group II (1.8%). The clinical course of asymptomatic paroxysmal AF is refractory to AAD when compared to symptomatic AF, meaning that anticoagulant therapy is required to prevent symptomatic thromboembolism in this group.


Financial Burden of Out-of-Pocket Expenditures for Primary Health Care in Hilly Areas of Garhwal Region, Uttarakhand, North India.
High total health expenditures via Out-of-Pocket (OOP) as formal user fees and informal payments put India in challenging situation to achieve towards universal health coverage. To assess the (OOP) expenditure and its determinants among outpatient in primary care settings of Uttarakhand, North India. A hospital based cross-sectional study was conducted in a Outpatient Department of Urban Health Training Centre, Srinagar, Uttarakhand, India and Rural Health Training Centre, Kritinagar, Uttarakhand in 2015. A total of 200 patients were enrolled in the study using random sampling. Questionnaire covering costs like: travel cost, drug cost, investigation cost, and others was used for measuring OOP expenditure incurred toward health care by patients. Of the total 200 patients, 43.5% were males and 56.5% were females with mean age 40.36 (SD 19.45) in years. Average annual family income was 11718.5 INR±13457.3 INR. Of the total study subjects, 42.5% were unskilled or had no occupation (unemployed, student, and homemaker). The majority (68.5%) had travelled less than or equal to 10 km to reach the health facility. About 50% of the study subjects presented with communicable diseases and 20% with non-communicable diseases. The health expenditure of the outpatient revealed that major part of the expenditure is the direct cost of the treatment, including registration fee, drugs, and investigation. Mean OOP expenditure for drugs and investigations was 509 INR and 673.1 INR, respectively. Mean total out-of-patient expenditure was 303.1 INR. The proportion of monthly family income spent on out-of-patient expenditure was 2.58%. The implementation of primary health care needs to be further strengthened in order to improve access of public sector hospitals for curative care.


Rapid prototyping in orthopaedic surgery: a user's guide.
Rapid prototyping (RP) is applicable to orthopaedic problems involving three dimensions, particularly fractures, deformities, and reconstruction. In the past, RP has been hampered by cost and difficulties accessing the appropriate expertise. Here we outline the history of rapid prototyping and furthermore a process using open-source software to produce a high fidelity physical model from CT data. This greatly mitigates the expense associated with the technique, allowing surgeons to produce precise models for preoperative planning and procedure rehearsal. We describe the method with an illustrative case.


Experience with vagotomy--antrectomy and Roux-en-Y gastrojejunostomy in surgical treatment of duodenal, gastric, and stomal ulcers.
Gastroduodenostomy (Billroth I) is our reconstruction of choice following gastric resection for gastroduodenal ulcer. Dissatisfaction with a Billroth II anastomosis has led us in recent years to employ a Roux-en-Y diversion in selected cases, particularly those in which the pathologic state of the pyloroduodenal canal would render a Billroth I anastomosis unsafe. During the past 7 years, truncal vagotomy-antrectomy and Roux-en-Y (VARY) has been carried out in 50 selected patients: duodenal ulcer (DU) 13 patients, gastric ulcer (GU) 11 patients, and stomal ulcer (SU) 26 patients. Fourteen patients (28%) developed postoperative complications, of which nine (18%) were of major degree and five (10%) of a lesser degree. No hospital death occurred among the 50 patients. Five patients (10%) developed postoperative delayed gastric emptying and two of the five required revision of the Roux. Forty-five patients had no clinical problems with delayed emptying. Overall results showed a Visick grading of I in 72%, Visick II in 24%, and Visick III in 4%. Further analysis revealed that of the 13 patients with DU who had VARY, 62% were Visick I, 30% Visick II, and 8% Visick III. The 11 GU patients with VARY were graded Visick I 73% and Visick II 27%. Of 26 patients with SU who underwent VARY, 77% were Visick I, 19% Visick II, and 4% Visick III. Mild to moderate dumping took place in 8% of the 50 patients, mild diarrhea 10%, weight loss 10%, and no patient experienced alkaline reflux gastritis. Long-range postoperative gastric emptying studies among nine patients using a radionuclide revealed varying patterns of emptying. Overall clinical results have been satisfactory and we are continuing to use VARY in selected cases, particularly those in which a Billroth I reconstruction appears contraindicated.


Induction of NK-like activity in T cells by IL-2/anti-CD3 is linked to expression of a new antitumour receptor with specificity for acetylated mannose.
The generation of MHC-unrestricted cytotoxicity of highly enriched human CD3+ T cells (95-99%) by treatment with IL-2 and/or anti-CD3 antibodies was studied. T cells obtained by positive immunomagnetic sorting (anti-CD3) developed comparable specific cytotoxicities against K562 and Daudi cells when cultured with IL-2 and anti-CD3 for 96 h (80% of donors; n = 25). This increase of MHC-unrestricted cytotoxicity correlated fairly well with an increased formation of T cell/tumour cell conjugates. Moreover, simultaneous expression of a rhamnogalacturonan-binding receptor on activated T cells could be demonstrated. Rhamnogalacturonan was reported to enhance cytotoxicity of CD56+ NK cells by effector cell/target cell bridging. Untreated CD3+ cells hardly reacted with rhamnogalacturonan and IL-2-activated T cells showed only a moderate enhancement of cytotoxicity in the presence of rhamnogalacturonan. However, when CD3+ T cells had interacted with anti-CD3 antibodies during cell-sorting or during subsequent culturing with IL-2, enhancement in cytotoxicity and increased formation of lytic effector cell/tumour cell conjugates in the presence of rhamnogalacturonan could be readily demonstrated, indicating a bridging effect analogous to CD56+ NK cells. The conjugate formation of activated T cells with tumour cells as well as the additional rhamnogalacturonan-mediated bridging must be based on the expression of receptors with acetyl mannose specificity, since enhancements of MHC-unrestricted T cell cytotoxicity and conjugate formation were inhibited in a dose-dependent manner when acetylated mannose was present in the assays.


History of Cardiovascular Surgery at Toronto General Hospital.
The Division of Cardiovascular Surgery at Toronto General Hospital has enjoyed an enviable history of academic achievement and clinical success. The foundations of this success are innovation, creativity and excellence in patient care, which continue to influence the current members of the division.


Is there any effect of oocyte count retrieved in the OPU procedure on pregnancy outcomes?
We aimed to investigate whether the number of oocytes retrieved during ovum pick-up has any effect on pregnancy outcomes when using the gonadotropin-releasing hormone or GnRH long agonist or antagonist protocols. A retrospective study was conducted between 2012 and 2014. The patients were grouped according to the number of oocytes retrieved at ovum pick-up; < 10 oocytes (Group 1), 10-14 oocytes (Group 2) and ≥ 15 oocytes (Group 3). Biochemical pregnancy rates were compared among the three groups. Statistical analysis was performed using one-way ANOVA test for continuous variables and chi-square test for categorical variables. In total, 825 treatment cycles were included in the study. Groups 1, 2 and 3 consisted of 514, 206 and 105 patients, respectively. There was no difference among the three groups regarding biochemical pregnancy rates (22.8%, 28.6% and 28.6%; p = 0.166, respectively). The results of our study suggest that the number of eggs retrieved has no effect on pregnancy outcome in assisted reproductive technology treatment.


Effects of different intensities of resistance training with equated volume load on muscle strength and hypertrophy.
The present study investigated the effects of different intensities of resistance training (RT) on elbow flexion and leg press one-repetition maximum (1RM) and muscle cross-sectional area (CSA). Thirty men volunteered to participate in an RT programme, performed twice a week for 12 weeks. The study employed a within-subject design, in which one leg and arm trained at 20% 1RM (G20) and the contralateral limb was randomly assigned to one of the three conditions: 40% (G40); 60% (G60), and 80% 1RM (G80). The G20 started RT session with three sets to failure. After G20 training, the number of sets was adjusted for the other contralateral limb conditions with volume-matched. CSA and 1RM were assessed at pre, post-6 weeks, and post-12 weeks. There was time effect for CSA for the vastus lateralis (VL) (8.9%, 20.5%, 20.4%, and 19.5%) and elbow flexors (EF) (11.4%, 25.3%, 25.1%, and 25%) in G20, G40, G60, and G80, respectively (p > .05). G80 showed higher CSA than G20 for VL (19.5% vs. 8.9%) and EF (25% vs. 11.4%) at post-12 weeks (p < .05). There was time effect for elbow flexion and unilateral leg press strength for all groups post-12 weeks (p < .05). However, the magnitude of increase was higher in G60 and G80. In conclusion, when low to high intensities of RT are performed with volume-matched, all intensities were effective for increasing muscle strength and size; however, 20% 1RM was suboptimal in this regard, and only the heavier RT intensity (80% 1RM) was shown superior for increasing strength and CSA compared to low intensities.


Compounds from Ilex paraguariensis extracts have antioxidant effects in the brains of rats subjected to chronic immobilization stress.
Immobilization induces oxidative damage to the brain. Ilex paraguariensis extracts (Mate) and their major natural compound, chlorogenic acid (CGA), exert protective effects against reactive oxygen species formation. Here, the effects of Mate and CGA on oxidative damage induced by chronic immobilization stress (CIS) in the cortex, hippocampus, and striatum were investigated. For CIS, animals were immobilized for 6 h every day for 21 consecutive days. Rats received Mate or CGA by intragastric gavage 30 min before every restraint session. Endpoints of oxidative stress (levels of lipid peroxidation, protein carbonylation, and reduced (GSH) and oxidized (GSSG) forms of glutathione) were evaluated following CIS. While CIS increased oxidized lipid and carbonyl levels in all brain regions, CGA (and Mate to a lesser extent) attenuated lipid and protein oxidation as compared with control groups. GSH/GSSG balance showed a tendency to increase in all regions in response to stress and antioxidants. Taken together, our results support a protective role of dietary antioxidants against the neuronal consequences of stress.


Duplication of the urethra.
Ten patients with patent urethral duplication are presented. Nine patients had two independent patient channels originating from the bladder or the posterior urethra. Both voiding cystourethro and retrograde urethrography are necessary to completely evaluate this anomaly. In each instance the ventral channel, regardless of the position of its meatus, proved to be the more functional urethra. In those patients whose dorsal channel was in an epispadiac position, the symphysis pubis was abnormally wide. A functionally and anatomically accurate classification is proposed, and the embryology of these anomalies is discussed.


Minimally invasive hip resurfacing.
Metal-on-metal hip resurfacing is an emerging surgical alternative for younger patients who are expected to outlive a conventional total hip replacement implant. Minimally invasive hip resurfacing uses a smaller surgical incision and new techniques to expose the hip joint. Possible advantages include less damage to soft tissue, muscle and bone; smaller scars; less blood loss; and shorter hospital stays and rehabilitation. Possible disadvantages include damage to soft tissue, femur fracture, neurovascular damage, implant malposition and a longer operating time. The lack of published or unpublished trials or case reports makes it impossible to draw conclusions about the relative effectiveness of minimally invasive procedures for hip resurfacing. Developments in computer navigation systems and fluoroscopic imaging may permit more widespread use of minimally invasive hip resurfacing in the future.


Efficient excitation-energy transfer in ion-based organic nanoparticles with versatile tunability of the fluorescence colours.
Organic nanoparticles consisting of 3,3'-diethylthiacyanine (TC) and ethidium (ETD) dyes are synthesized by ion-association between the cationic dye mixture (10 % ETD doping) and the tetrakis(4-fluorophenyl)borate (TFPB) anion, in the presence of a neutral stabilizing polymer, in aqueous solution. Doping with ETD makes the particle size smaller than without doping. Size tuning can also be conducted by varying the molar ratio (ρ) of the loaded anion to the cationic dyes. The fluorescence spectrum of TC shows good overlap with the absorption of ETD in the 450-600 nm wavelength region, so efficient excitation-energy transfer from TC (donor) to ETD (acceptor) is observed, yielding organic nanoparticles whose fluorescence colours are tunable. Upon ETD doping, the emission colour changes significantly from greenish-blue to reddish or whitish. This change is mainly dependent on ρ. For the doped nanoparticle sample with ρ=1, the intensity of fluorescence ascribed to ETD is ∼150-fold higher than that from pure ETD nanoparticles (efficient antenna effect). Non-radiative Förster resonance-energy transfer (FRET) is the dominant mechanism for the ETD fluorescence enhancement. The organic nanoparticles of a binary dye system fabricated by the ion-association method act as efficient light-harvesting antennae, which are capable of transferring light energy to the dopant acceptors in very close proximity to the donors, and can have multi-wavelength emission colours with high fluorescence quantum yields.


Integration of clinical pharmacists to assist with medication surveillance for patients receiving gender-affirming hormone therapy in a community ambulatory setting within the United States.
Gender-affirming care (GAC) for gender diverse individuals (includes transgender and non-binary persons), requires a comprehensive approach to medication surveillance, including monitoring and follow-up. Limited access to these health services can present a barrier to follow-up for routine care. Integration of a pharmacist into therapeutic management has shown positive clinical outcomes, however their involvement with gender-affirming hormone therapy (GAHT), including routine laboratory monitoring, is not well established. To describe the development and implementation of a protocol involving the integration of clinical pharmacists into GAC for gender diverse patients in a community ambulatory setting. Cleveland Clinic's Center for LGBTQ+ Care is embedded in a primary care practice and has an established protocol for GAHT management. The health system also has an established model that utilizes pharmacists for the management of patients, within the primary care and specialty clinic settings, under a collaborative practice agreement (CPA). The medical director of the Cleveland Clinic's Center for LGBTQ+ Care and the institution's primary care pharmacists collaborated to propose an update to the CPA to include GAHT monitoring to improve access to routine GAHT follow-up. GAHT management was approved to be added to the pharmacist CPA in May of 2022 and the pharmacists started seeing patients in February of 2023. The team opted to start with those patients already established on GAHT for at least 6 months, at least 1-year post-transition, and with a primary care provider managing their GAHT. Access to follow-up for individuals receiving GAHT may be improved through the utilization of pharmacist services. The incorporation of a CPA with pharmacists for GAHT management can allow for a multidisciplinary approach once a patient is on a stable regimen, thereby increasing provider access to new patients.


Ethnicity and Smoking-Associated DNA Methylation Changes at HIV Co-Receptor GPR15.
Smoking is associated with poorer health outcomes for both African and European Americans. In order to better understand whether ethnic-specific genetic variation may underlie some of these differences, we compared the smoking-associated genome-wide methylation signatures of African Americans with those of European Americans, and followed up this analysis with a focused examination of the most ethnically divergent locus, cg19859270, at the GPR15 gene. We examined the association of methylation at this locus to the rs2230344 SNP and GPR15 gene and protein expression. Consistent with prior analyses, AHRR residue cg05575921 was the most differentially methylated residue in both African Americans and European Americans. However, the second most differentially methylated locus in African Americans, cg19859270, was only modestly differentially methylated in European Americans. Interrogation of the methylation status of this CpG residue found in GPR15, a chemokine receptor involved in HIV pathogenesis, showed a significant interaction of ethnicity with smoking as well as a marginal effect of genotype at rs2230344, a neighboring non-synonymous SNP, but only among African Americans. Gene and protein expression analyses showed that demethylation at cg19859270 was associated with an increase in both mRNA and protein levels. Since GPR15 is involved in the early stages of viral replication for some HIV-1 and HIV-2 isolates, and the prevalence of HIV is increased in African Americans and smokers, these data support a possible role for GPR15 in the ethnically dependent differential prevalence of HIV.


Kondo-Dicke resonances in electronic transport through double quantum dots.
Electronic transport through a system of two quantum dots coupled to external leads is considered theoretically. The dots are assumed to be in the Kondo regime, and the infinite-U mean-field slave-boson approach is used to obtain basic transport characteristics. Density of states and electron transmission probability in the Kondo regime are considered and calculated numerically. Both quantities are shown to exhibit features that are typical of the Dicke resonance.


Acute care for elders units produced shorter hospital stays at lower cost while maintaining patients' functional status.
Acute Care for Elders Units offer enhanced care for older adults in specially designed hospital units. The care is delivered by interdisciplinary teams, which can include geriatricians, advanced practice nurses, social workers, pharmacists, and physical therapists. In a randomized controlled trial of 1,632 elderly patients, length-of-stay was significantly shorter-6.7 days per patient versus 7.3 days per patient-among those receiving care in the Acute Care for Elders Unit compared to usual care. This difference produced lower total inpatient costs-$9,477 per patient versus $10,451 per patient-while maintaining patients' functional abilities and not increasing hospital readmission rates. The practices of Acute Care for Elders Units, and the principles they embody, can provide hospitals with effective strategies for lowering costs while preserving quality of care for hospitalized elders.


Predicting MicroRNA Mediated Gene Regulation between Human and Viruses.
MicroRNAs (miRNAs) mediate various biological processes by actively fine-tuning gene expression at the post-transcriptional level. With the identification of numerous human and viral miRNAs, growing evidence has indicated a common role of miRNAs in mediating the interactions between humans and viruses. However, there is only limited information about Cross-Kingdom miRNA target sites from studies. To facilitate an extensive investigation on the interplay among the gene regulatory networks of humans and viruses, we designed a prediction pipeline, mirTarP, that is suitable for miRNA target screening on the genome scale. By applying mirTarP, we constructed the database mirTar, which is a comprehensive miRNA target repository of bidirectional interspecies regulation between viruses and humans. To provide convenient downloading for users from both the molecular biology field and medical field, mirTar classifies viruses according to "ICTV viral category" and the "medical microbiology classification" on the web page. The mirTar database and mirTarP tool are freely available online.


Effects of epinephrine infusion on determinants of intravenous glucose tolerance in dogs.
Effects of four- to fivefold elevations of epinephrine (EPI) on glucose (Glc) metabolism were assessed in eight dogs before and after an intravenous Glc tolerance test, performed 30 min (short EPI) and 72 h (long EPI) after start of EPI infusion. Short EPI increased plasma nonesterified fatty acids (NEFA; 0.46 +/- 0.08 to 0.78 +/- 0.12 mmol/l, P less than 0.05), but Glc and insulin were unchanged. After long EPI, NEFA returned to control but Glc increased from 5.1 +/- 0.1 to 5.7 +/- 0.2 mmol/l (P less than 0.05). EPI reduced overall Glc tolerance (KG) from 3.5 +/- 0.7 to 2.5 +/- 0.2 (short EPI, P less than 0.05) and 2.3 +/- 0.3%/min (long EPI, P less than 0.02). Minimal model analysis showed that short EPI decreased insulin sensitivity (SI) from 7.9 +/- 1.1 to 4.2 +/- 1.2 min-1 per mU/l X 10(-4) (P less than 0.005) and increased pancreatic responsiveness (phi 1 from 3.7 +/- 0.3 to 7.4 +/- 2.9 mU/l.min-1 per mg/dl, P less than 0.025; phi 2 from 2.6 +/- 0.7 to 4.9 +/- 1.2 mU/l.min-2 per mg/dl). After long EPI SI, phi 1, and phi 2 returned to control. In contrast, Glc-mediated Glc disposal (SG) was decreased from 3.5 +/- 0.5 X 10(-2) to 2.8 +/- 0.6 X 10(-2) (short EPI) and 1.3 +/- 0.6 X 10(-2) min-1 (long EPI, P less than 0.02). We conclude that prolonged infusion of EPI leads to adaptation to its acute effects on NEFA, SI, phi 1, and phi 2.(ABSTRACT TRUNCATED AT 250 WORDS)


Modulation of steroidogenesis by chloride ions in MA-10 mouse tumor Leydig cells: roles of calcium, protein synthesis, and the steroidogenic acute regulatory protein.
It has previously been shown that omission of extracellular chloride ions during culture of rat Leydig cells markedly enhances LH-stimulated steroidogenesis. In the present study, the mechanisms of the effect of chloride omission on (Bu)2cAMP-stimulated steroidogenesis in MA-10 mouse Leydig tumor cells have been investigated. It was found that chloride omission enhanced progesterone production 2- and 4-fold in the absence and presence, respectively, of submaximally stimulating levels of (Bu)2cAMP (0.1 mM) during incubation for 2 h. This enhancement of stimulation increased continuously with time, because after 6 h, (Bu)2cAMP-stimulated progesterone production was 15-fold higher in the absence of chloride. These effects were not found in the presence of maximum stimulating levels of (Bu)2cAMP (1 mM). Omission of calcium from the incubation medium decreased (Bu)2cAMP-stimulated progesterone production by over 70% in the presence and absence of chloride. Progesterone production was still enhanced by the omission of chloride in the absence of calcium, but the effects were less marked than those in the presence of calcium. Addition of the protein synthesis inhibitor, cycloheximide, completely inhibited (Bu)2cAMP-stimulated, but not basal, steroidogenesis in the absence and presence of chloride ions during 2- and 6-h incubation. Total protein synthesis (measured by the incorporation of [3H]methionine) was 4-fold higher in cells incubated in chloride-free medium compared with that in cells incubated in chloride-replete medium in the presence of 0.1 mM (Bu)2cAMP. No effects were found on basal levels. Several proteins specific to the steroidogenic machinery were quantified in mitochondria isolated from cells incubated with and without chloride by Western blot analysis after separation by PAGE. Omission of chloride increased (4-fold) the level of the steroidogenic acute regulatory (StAR) protein in the cells incubated with (Bu)2cAMP (0.1 mM). There was no increase in either the levels or activities of cytochrome P450 cholesterol side-chain cleavage enzyme (cytP450scc) or 3beta-hydroxysteroid dehydrogenase. No effects were found on the basal level of any of the proteins measured. These results are consistent with a cAMP-dependent regulatory role of chloride ion efflux in the control of steroidogenesis, which requires protein synthesis. It is proposed that this occurs by increases in StAR protein synthesis via a general increase in cAMP-dependent protein synthesis and/or by enhancement of the steroidogenic effects of StAR.


[Follow-up and management of Coats disease diagnosed in childhood].
To investigate retrospectively the clinical manifestation and the final visual prognosis through a long-term fellow-up study. It was retrospective case series study. Twenty four patients (26 eyes) were diagnosed with Coats disease from 1962 through 2006 at the Department of Ophthalmology, Peking Union Medical Hospital, Chinese Academy of Medical Sciences. Age, visual acuity, time of initial visit, method of treatment and the condition of eye fundus for each patient were documented. The time of follow-up ranged from 1-44 years, averaged 5 years. Age of the patients at initial visit ranged between 1 to 18 years old, 7 years on average. Eighteen patients (75%) were male and 6 were female (25%). Twenty two cases were unilateral and only 2 female patients were bilateral. In 26 eyes, 7 eyes exhibited capillary irregular dilatation, miliary aneurysms and nonperfusion area on fluorescein angiography located at peripheral fundus; 15 eyes were complicated with exudative retinal detachment. Four eyes reached end stage with no light perception or only finger count. Laser photocoagulation was performed in 21 eyes. In 10 eyes, retinal exudates and hemorrhages were absorbed with improvement of visual acuity. Ten eyes with extensive retinal detachment including macula underwent closed vitrectomy, the best visual acuity was 0.1 after surgery. The onset of Coats disease is in early young childhood. Abnormal vascular lesions and military aneurysms appeared at peripheral fundus with early retinal exudation involving the macula. Early treatment with laser coagulation could obtain good visual prognosis. The supplement treatment is required for new lesions occurring during the long- term follow-up period.


Probiotic-fermented tomato alleviates high-fat diet-induced obesity in mice: Insights from microbiome and metabolomics.
Probiotic-fermented plant-based foods are associated with weight loss. Here, we hypothesized probiotic-fermented tomato (FT) as a functional food with potential to alleviate obesity, thus the obesity-alleviating effects and mechanisms of FT on high-fat diet-induced obese mice were explored via biochemical, gut microbiome, and serum metabolomics analysis. The results showed that FT performed better than unfermented tomato in reducing body weight gain and fat accumulation, improving dyslipidemia and glucose homeostasis, and relieving inflammation and adipocytokine dysregulation. Particularly, live probiotic-fermented tomato (LFT) was associated with improved diversity, composition, and structure of gut microbiota, suppressed obesity-related genera growth (e.g., Clostridium, Olsenella, and Mucispirillum), and promoted beneficial genera growth (e.g., Roseburia, Coprococcus, and Oscillospira), which were associated negatively with body weight, TC, TG, and TNF-α levels. Additionally, LFT was associated with positive changes in glycerophospholipids, sphingolipids, unsaturated fatty acids, and amino acids levels. Collectively, as a functional food, LFT possessed potential for obesity alleviation.


Essential considerations in the provision of near-patient testing facilities.
(1) Near-patient testing (NPT) is both practicable and in some situations desirable. (2) Like all new technologies its apparent simplicity often belies its complexity and masks the need for attention to detail in order to achieve optimum effects and avoid disasters. (3) Though technically unskilled individuals are capable of using it, they must undergo training in the elements of safety, sample collection, quality control, quantitation and documentation before being authorized to provide analytical services for patients. (4) Health Authorities should be encouraged to adopt a policy of integration of NPT and clinical laboratory services in order to reduce unplanned use and abuse of NPT facilities which is not only wasteful and divisive, but also dangerous. This has recently been emphasized in the United Kingdom by the release of a Hazard Notice (HN (Hazard) (87) 13) by the Department of Health and Social Security. The experienced clinical biochemist will, by virtue of training and experience, usually be the most suitable person in a Health District to advise on many of the issues involved in NPT. It should therefore, be the responsibility of laboratory staff to work with management, clinical, and nursing staff to: choose appropriate sites for the various levels of service to be provided to meet a clinical need; select the equipment and reagents to be employed; provide training in the use of the apparatus, quality control and safety; authorize accredited users and oversee the quality assurance programme. (5) Laboratory staff will need to involve themselves closely in the financial implications of NPT both for the laboratory's benefit and that of clinical practice within the hospital and/or community as a whole.


Effects of levamisole on normal and malignant murine lymphocytes.
Levamisole enhanced transformation of murine lymphocytes stimulated either by mitogens or allogeneic lymphocytes. In a similar dose-dependent pattern it stimulated in vitro growth of L1210, P1798, and 6C3HED but not YAC lymphoma cells. Stimulation of growth of lymphoma cells was greater by peritoneal cells harvested from normal mice 4 days after levamisole injection than by peritoneal cells from untreated mice. This effect correlated with the shortened survival time of BALB/c mice treated with levamisole prior to P1798 implantation compared to that of a control group not pretreated. Administration of levamisole with iodoacetamide-modified tumor cells in immunoprophylaxis studies had no effect on the rejection of a tumor implant or on development of tumor-specific antibody. Levamisole was added to regimens involving asparaginase therapy of 6C3HED-bearing C3H mice and chemoimmunotherapy of BALB/c mice bearing P1798 with methotrexate and iodoacetamide-modified P1798 cells. In neither case were there increased numbers of survivors, and mean survival time was generally decreased for the levamisole-treated groups. The stimulated tumor growth may have been mediated by a direct effect of levamisole on the lymphoma cells, through an effect on other cell types, or by both effects; these effects apparently outweighed potentially beneficial effects of levamisole on the immune system.


In vitro Characterization of the Rapid Cytotoxicity of Anticancer Peptide HPRP-A2 through Membrane Destruction and Intracellular Mechanism against Gastric Cancer Cell Lines.
In this study, HPRP-A2, a synthetic 15-mer cationic peptides with all D-amino acids, effectively inhibited the survival of gastric cell lines in a dose-dependent manner. Gastric tumor cells killing by HPRP-A2 involves a rapid collapse of the membrane integrity and intracellular pathways. Propidium iodide (PI) and lactate dehydrogenase (LDH) assays demonstrated that one-hour treatment with HPRP-A2 led to membrane permeability changes of BGC-823 cells in a dose-dependent manner. Moreover, HPRP-A2 induced apoptosis in BGC-823 cells involves a marked increase in generation of reactive oxygen species (ROS),caspase-3, -8 and -9 activation, a reduction of mitochondrial membrane potential (MMP), and cell cycle arrest in G1 phase. In addition to its inherent cytotoxicity, HPRP-A2 synergized strongly with doxorubicin (DOX) to enhance the efficacy of killing gastric tumor cells in vitro. We believe that HPRP-A2 with all D-amino acids could be a potent candidate of anticancer therapeutics, especially in combination therapy.


Electron spin polarization of the excited quartet state of strongly coupled triplet-doublet spin systems.
The electron spin polarization associated with electronic relaxation in molecules with trip-quartet and trip-doublet excited states is calculated. Such molecules typically relax to the lowest trip-quartet state via intersystem crossing from the trip doublet, and it is shown that when spin-orbit coupling provides the main mechanism for this relaxation pathway it leads to spin polarization of the trip quartet. Analytical expressions for this polarization are derived using first- and second-order perturbation theory and are used to calculate powder spectra for typical sets of magnetic parameters. It is shown that both net and multiplet contributions to the polarization occur and that these can be separated in the spectrum as a result of the different orientation dependences of the +/-1/2<-->+/-3/2 and +1/2<-->-1/2 transitions. The net polarization is found to be localized primarily in the center of the spectrum, while the multiplet contribution dominates in the outer wings. Despite the fact that the multiplet polarization is much stronger than the net polarization for individual orientations of the spin system, the difference in orientation dependence of the transitions leads to comparable amplitudes for the two contributions in the powder spectrum. The influence of this difference on the line shape is investigated in simulations of partially ordered samples. Because the initial nonpolarized state of the spin system is not conserved for the proposed mechanism, the net polarization can survive in the doublet ground state following electronic relaxation of the triplet part of the system.


Sound order discrimination in two species of birds-Taeniopygia guttata and Melopsittacus undulatus.
Recent psychophysical experiments have shown that zebra finches (Taeniopygia guttata-a songbird) are surprisingly insensitive to syllable sequence changes in their species-specific motifs while budgerigars (Melopsittacus undulatus-a psittacine) do much better when tested on exactly the same sounds. This is unexpected since zebra finch males learn the order of syllables in their songs when young and sing the same song throughout adulthood. Here we probe the limits of this species difference by testing birds on an order change involving just two syllables, hereafter called bi-syllable phrases. Results show budgerigars still perform better than zebra finches on an order change involving just two syllables. An analysis of response latencies shows that both species respond to an order change in a bi-syllable motif at the onset of the first syllable rather than listening to the entire sequence before responding. Additional tests with one syllable omitted or doubled, or with white noise bursts substituted for syllables, indicate that the first syllable in the sequence has a dominant effect on subsequent discrimination of changes in a bi-syllable pattern. These results are surprising in that zebra finch males sing their full motif syllable sequence with a high degree of stereotypy throughout life, suggesting that this consistency in production may not rely on perceptual mechanisms for processing syllable order in adulthood. Budgerigars, on the other hand, are quite sensitive to bi-syllable order changes, an ability that may be related to useful information being encoded in the sequence of syllables in their natural song. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Influence of propofol intravenous anesthesia on hemorheology, haemodynamics and immune function of colorectal carcinoma patients undergoing radical resection.
To analyze the changes of hemorheology, haemodynamics and immune function of patients during propofol intravenous anesthesia in the radical resection of colorectal carcinoma and its significance. The study included 112 patients who underwent radical resection of colorectal carcinoma in our hospital between August 2016 and December 2017, and they were divided into an observation group (N=56) and a control group (N=56) using random number table. Patients in the observation group were given propofol intravenous anesthesia, while patients in the control group received inhalation anesthesia of sevoflurane. Hemorheological and haemodynamical indexes were compared and analyzed before anesthesia (T0), 90 min after induction (T1), 150 min after induction (T2) and 30 min after entering post-anesthesia care unit (T3), and the changes of immune function before and after surgery was also observed. The whole blood viscosity under high, medium and low shear rates of the observation group declined significantly compared to that of the control group at T1, T2 and T3 (P<0.05). The heart rate (HR) and systolic pressure (SPB) of the observation group significantly decreased at T2 compared to those at T1 (P<0.05), but recovered to the level observed at T0 at T3. The diastolic blood pressure (DBP) of the two groups at T1, T2 and T3 was not significantly different with that at T0 (P>0.05). The levels of CD45RA+ and CD45RO+ of both groups had a significant decrease at the end of the surgery compared to before anesthesia (P<0.05); the levels of the observation group recovered at the postoperative 72nd h, and the differences with the levels before anesthesia had no statistical significance (P>0.05); the level of CD45RA+ of the control group also recovered at the postoperative 72nd h, but the difference with the level before anesthesia had no statistical significance (P>0.05); the level of CD45RO+ of the control group had a significant decrease, and the difference with the level before anesthesia was statistically significant (P<0.05). The level of CD45RA+/CD45RO+ of the observation group at the end of surgery and the postoperative 72nd h was not significantly different with those before anesthesia (P>0.05). The level of CD45RA+/CD45RO+ of the control group at the postoperative 72nd h showed a significant increase compared to before anesthesia (P<0.05). Propofol intravenous anesthesia has a significant improvement effect on hemorheology before radical resection of colorectal carcinoma and has a small influence on haemodynamics. Moreover it is beneficial to the recovery of immune function. The therapy is worth promotion.


Perinodular Vascularity Distinguishes Benign Intrapulmonary Lymph Nodes From Lung Cancer on Computed Tomography.
A common diagnostic dilemma in the assessment of small pulmonary nodules on computed tomography (CT) is in distinguishing benign intrapulmonary lymph nodes (IPLNs) from small primary pulmonary malignancies. Several CT features have been described of IPLNs, including attachment to a pleural surface. We had observed that IPLNs were often connected to a pulmonary vein and sought to evaluate the utility of this sign in discriminating IPLNs from lung adenocarcinomas. The frequency of other previously described CT signs of IPLNs was also compared with lung adenocarcinomas. We retrospectively identified histopathologically proven benign IPLNs (n=62) and small (<15 mm) adenocarcinomas (n=61). CTs were reviewed to assess the number and type of pulmonary blood vessels arising from, or terminating within, these nodules, as well as other CT features of IPLNs (shape, location, and outline). The termination of a pulmonary artery within a nodule was strongly associated with primary lung adenocarcinoma (55.7%), and this was never seen in isolation in IPLNs (0%) (P<0.001). IPLNs were more frequently associated with pulmonary venous connections (93.5%) compared with lung adenocarcinomas (21.3%) (P<0.001). The connection to a pleural surface was observed in both IPLNs (38.7%) and lung adenocarcinomas (37.7%) (P=1.0). We describe a novel imaging marker that can help to differentiate between benign and malignant pulmonary nodules. However, attachment of a nodule to a pleural surface should not be used in isolation to distinguish IPLNs from lung malignancy.


A Case of Elephantiasic Pretibial Myxedema Successfully Treated With Intralesional Triamcinolone Acetate.
Graves' dermopathy is one of the extra-thyroidal manifestations of Graves' disease (GD) and is characterized by the accumulation of glycosaminoglycans in the reticular dermis. In the majority of cases, pretibial myxedema is self-limiting but, in some cases, it can lead to structural and functional damage. Topical steroids with occlusive dressing remain the conventional treatment, but intralesional steroids have shown promising results. We hereby present a case of pretibial myxedema treated successfully with intralesional triamcinolone acetate.


Once daily lisinopril and captopril in hypertension: a double blind comparison using ambulatory monitoring.
To validate and compare the 24-hour antihypertensive efficacy of the angiotensin-converting-enzyme inhibitors, captopril and lisinopril. A randomised, doubleblind, doubledummy crossover study was performed with single-blind placebo run-in and washout periods and titration opportunities during therapeutic phases (captopril 25mg, 50mg and 100mg daily, lisinopril 10mg, 20mg and 40mg daily). The study was monitored using standard office blood pressure measurements, clinical and laboratory assessment. 24 patients of either sex and between 18 and 70 years with essential hypertension were enrolled, 20 met randomisation criteria (of sitting diastolic pressure 95-115mmHg), 3 withdrew from the study during its active phase and one was excluded from analysis having been found retrospectively to have not met randomisation criteria at the appropriate visit. Predetermined endpoints were blood pressure levels during different time periods of ambulatory monitoring performed at the end of each placebo or treatment phase. In the 17 patients who completed the protocol, lisinopril produced a greater reduction of blood pressure at all time periods although the differences were not all statistically significant. The differences were most marked 19-24 hours post dosage time when pressures (systolic/diastolic) during lisinopril therapy were lower than during captopril by 18.0/14.5 mmHg (p < 0.001 for both). As measured by clinic pressures, lisinopril also achieved a considerably higher degree of blood pressure control with less dose titration. In this study, lisinopril proved a more effective once daily antihypertensive agent than captopril, especially in the last 6 hours of the 24-hour dosage interval.


Validated Chiral LC-ESI-MS/MS Method for the Simultaneous Quantification of Darolutamide Diastereomers and Its Active Metabolite in Mice Plasma: Application to a Pharmacokinetic Study.
A simple, selective and reliable LC-MS/MS method was developed and validated for the simultaneous quantitation of darolutamide diastereomers (diastereomer-1 and diastereomer-2) and its active metabolite i. e. ORM-15341 in mice plasma using warfarin as an internal standard (IS) as per the regulatory guidelines. Plasma samples were extracted by liquid-liquid extraction and the chromatographic separation was achieved on a Chiralpak IA column with an isocratic mobile phase 5 mM ammonium acetate:absolute alcohol (20:80, v/v) at a flow rate of 1.0 mL/min. Detection and quantitation was done by multiple reaction monitoring on a triple quadrupole mass spectrometer following the transitions: m/z 397→202, 395→202 and 307→250 for darolutamide diastereomers, ORM-15341 and the IS, respectively in the negative ionization mode. The calibration curves were linear (r>0.992) in the range of 100-2400 ng/mL for all the analytes. The intra- and inter-day precisions were in the range of 1.25-10.2 and 1.58-12.3; 2.85-5.68 and 1.85-9.58; 2.34-12.1 and 2.58-7.38 for diastereomer-1, diastereomer-2 and ORM-15341, respectively. Both diastereomers and ORM-15341 were found to be stable under different stability conditions. The validated method was applied to a pharmacokinetic study in mice.


Pharmaceutical approval update.
Ledipasvir/sofosbuvir (Harvoni) for hepatitis C virus genotype 1 infection; dulaglutide (Trulicity) for glycemic control in type-2 diabetes; netupitant/palonosetron (Akynzeo) for prevention of nausea and vomiting related to chemotherapy; and naloxegol (Movantik) for opioid-induced constipation in patients with chronic noncancer pain.


Neurogenic Monodermal Teratoma in the Scapula of a Child: A Case Report.
Background: Neurogenic monodermal teratomas (NMTs) have been reported in the ovaries but not from bone. Case Report: A 6-year-old girl had an incidentally discovered lesion in the right scapula. Upon removal, it was an NMT with predominant choroid plexus. The disease had not progressed for 31 months. Conclusion: Neurogenic monodermal teratomas can also occur in bone.


Imaging β-amyloid using [(18)F]flutemetamol positron emission tomography: from dosimetry to clinical diagnosis.
In Alzheimer's disease (AD), the deposition of β-amyloid (Aβ) is hypothesized to result in a series of secondary neurodegenerative processes, leading ultimately to synaptic dysfunction and neuronal loss. Since the advent of the first Aβ-specific positron emission tomography (PET) ligand, (11)C-Pittsburgh compound B ([(11)C]PIB), several (18)F ligands have been developed that circumvent the limitations of [(11)C]PIB tied to its short half-life. To date, three such compounds have been approved for clinical use by the US and European regulatory bodies, including [(18)F]AV-45 ([(18)F]florbetapir; Amyvid™), [(18)F]-BAY94-9172 ([(18)F]florbetaben; Neuraceq™) and [(18)F]3'-F-PIB ([(18)F]flutemetamol; Vizamyl™). The present review aims to summarize and discuss the currently available knowledge on [(18)F]flutemetamol PET. As the (18)F analogue of [(11)C]PIB, [(18)F]flutemetamol may be of use in the differentiation of AD from related neurodegenerative disorders and may help with subject selection and measurement of target engagement in the context of clinical trials testing anti-amyloid therapeutics. We will also discuss its potential use in non-AD amyloidopathies.


Personality disorders as an expression of the dimensional polarity in personality development in late adulthood women.
Relationships between Axis II personality disorders and Sidney Blatt constructs of dependency and self-criticism were explored in a late adulthood women sample. The sample consisted of 102 women (M = 72.07 years of age, SD = 7.04) who were administered two measures, the Personality Diagnostic Questionnaire-4+ and the Depressive Experiences Questionnaire. The histrionic, dependent, and obsessive-compulsive personality disorder scales are shown to be significant predictors of dependency, and the narcissistic, borderline, and avoidant scales are significant predictors of self-criticism. The application of a dimensional interpersonal approach to psychopathology is discussed.


Bicoid cooperative DNA binding is critical for embryonic patterning in Drosophila.
Cooperative interactions by DNA-binding proteins have been implicated in cell-fate decisions in a variety of organisms. To date, however, there are few examples in which the importance of such interactions has been explicitly tested in vivo. Here, we tested the importance of cooperative DNA binding by the Bicoid protein in establishing a pattern along the anterior-posterior axis of the early Drosophila embryo. We found that bicoid mutants specifically defective in cooperative DNA binding fail to direct proper development of the head and thorax, leading to embryonic lethality. The mutants did not faithfully stimulate transcription of downstream target genes such as hunchback (hb), giant, and Krüppel. Quantitative analysis of gene expression in vivo indicated that bcd cooperativity mutants were unable to accurately direct the extent to which hb is expressed along the anterior-posterior axis and displayed a reduced ability to generate sharp on/off transitions for hb gene expression. These failures in precise transcriptional control demonstrate the importance of cooperative DNA binding for embryonic patterning in vivo.


Developmental expression of Commd1 in the liver of the Jackson toxic milk mouse.
Wilson disease (WD) is due to mutations in ATP7B, which encodes an intracellular metal-transporting P-type ATPase. In WD holoceruloplasmin production and biliary excretion of copper are decreased, leading to copper overload, oxidative stress and apoptotic cell death. Other copper-binding proteins include COMMD1, which is inactive in the Bedlington terrier hereditary copper toxicosis, and XIAP, which regulates apoptosis. We examined developmental expression of Commd1 and Xiap in the Jackson toxic milk mouse (Atp7b(tx-J), G712D missense mutation in Atp7b). Expression of Commd1 mRNA appeared unchanged by PCR but real-time PCR demonstrated 3- to 4-fold increase over the first 6 months of life. Immunodetectable Xiap dropped over the first 8 months of life and was nearly undetectable from 6 months onward. Cytosolic NF-kappaB rose then dropped precipitously at 5-6 months. In tx-j mice hepatic copper accumulation leads to decreased Xiap, increased Commd1; these responses ultimately fail to prevent progressive apoptotic cell damage.


Human iPS cell models of Jervell and Lange-Nielsen syndrome.
Recessive mutations in the ion channel-encoding KCNQ1 gene may cause Jervell and Lange-Nielsen syndrome (JLNS), a fatal cardiac disease leading to arrhythmia and sudden cardiac death in young patients. Mutations in KCNQ1 may also cause a milder and dominantly inherited form of the disease, long QT syndrome 1 (LQT1). However, why some mutations cause LQT1 and others cause JLNS can often not be understood a priori. In a recent study,(1) we have generated human induced pluripotent stem cell (hiPSC) models of JLNS. Our work mechanistically revealed how distinct classes of JLNS-causing genetic lesions, namely, missense and splice-site mutations, may promote the typical severe features of the disease at the cellular level. Interestingly, the JLNS models also displayed highly sensitive responses to pro-arrhythmic stresses. We hence propose JLNS hiPSCs as a powerful system for evaluating both phenotype-correcting as well as cardiotoxicity-causing drug effects.


Avulsion fracture of the foramen magnum treated with occiput-to-c1 fusion: technical case report.
A 31-year-old woman presented with an avulsion fracture of the foramen magnum via bilateral occipital condyles with extension through the inferior aspect of the clivus. The patient had no neurological deficits and was initially immobilized in a halo brace. To preserve rotational motion at C1-C2, we performed an occiput-to-C1 fusion with bilateral C1 lateral mass screws attached with rods to occipital keel screws. Postoperatively, the patient remained neurologically intact. Three-month follow-up imaging revealed no abnormal motion. Follow-up computed tomographic scan showed an intact construct and bony fusion. This rare injury, a bony variant of occipitoatlantal dislocation, was successfully treated with a unique occiput-to-C1 fusion.


West Nile Virus detection in kidney, cloacal, and nasopharyngeal specimens.
We compared kidney tissue samples and cloacal and nasopharyngeal swab samples from field-collected dead crows and blue jays for West Nile virus surveillance. Compared to tissue samples, 35% more swab samples were false negative. Swab samples were usually positive only when the corresponding tissue sample was strongly positive.


Selective Retinoic Acid Receptor γ Antagonist 7C is a Potent Enhancer of BMP-Induced Ectopic Endochondral Bone Formation.
Bone morphogenetic proteins (BMPs) have been clinically applied for induction of bone formation in musculoskeletal disorders such as critical-sized bone defects, nonunions, and spinal fusion surgeries. However, the use of supraphysiological doses of BMP caused adverse events, which were sometimes life-threatening. Therefore, safer treatment strategies for bone regeneration have been sought for decades. Systemic administration of a potent selective antagonist of retinoic acid nuclear receptor gamma (RARγ) (7C) stimulated BMP-induced ectopic bone formation. In this study, we developed 7C-loaded poly lactic nanoparticles (7C-NPs) and examined whether local application of 7C enhances BMP-induced bone regeneration. The collagen sponge discs that absorbed recombinant human (rh) BMP-2 were implanted into the dorsal fascia of young adult mice to induce ectopic bone. The combination of rhBMP-2 and 7C-NP markedly increased the total bone volume and thickness of the bone shell of the ectopic bone in a dose-dependent manner compared to those with rhBMP-2 only. 7C stimulated sulfated proteoglycan production, expression of chondrogenic marker genes, and Sox9 reporter activity in both chondrogenic cells and MSCs. The findings suggest that selective RARγ antagonist 7C or the related compounds potentiate the bone inductive ability of rhBMP-2, as well as support any future research to improve the BMP-2 based bone regeneration procedures in a safe and efficient manner.


Initial Experiences with the MitraClip G4: Review of the Novel Device Features.
Percutaneous edge-to-edge mitral valve repair is an evolving procedure with increasing indications for use. The MitraClip™ G4 is the newest device with 4 device options, each with distinct characteristics. While the NTR and XTR clips have been in use, the G4 adds 2 new wider clips with additional features, the NTW and XTW. We reviewed 26 cases employing the MitraClip G4 at our institution from November 2019 to March 2020. The NTR, XTR, NTW, and XTW clips were used in 3 (11.5%), 0 (0.0%), 16 (61.5%), and 11 (42.3%) cases, respectively. Median mitral regurgitation grade was reduced from 4+ to 1+, though 7 (27%) cases had 2+ residual mitral regurgitation. The new G4 device includes simplified instructions for use, the option of a wider clip, controlled gripper actuation, and potential left atrial pressure monitoring. The newest MitraClip G4 device allows for potential improved treatment options for patients with mitral regurgitation.


[Levobupivacaine for Ultrasound-guided Interscalene Block: Block with 6 ml Leads to Less Occurrence of Respiratory Depression and Hemidiaphragmatic Paralysis].
Interscalene brachial plexus block (ISBPB) complications depend usually on the dose administered. The object of this study was to determine whether ultrasound-guided ISBPB with 6 ml of 0.5% levobupivacaine would reduce occurrence of respiratory depression and hemidiaphragmatic paralysis. Patients undergoing arthroscopic shoulder surgery under nerve block with general anesthesia (n = 20) were recruited. There were no differences between pre and post operative respiratory function (forced expiratory volume 1.0 (sec) % and vital capacity). Hemidiaphragmatic paralysis on postoperative ultrasonography was found in two patients. The use of low-volume ultrasound-guided ISBPB is associated with less respiratory depression and hemidiaphragmatic paralysis.


Management and outcomes of peptic ulcer disease in pregnancy.
Given the altered physiology of pregnancy, gastroenterologists are often reluctant to perform endoscopic procedures in pregnant women. The purpose of our study was to compare management practices and outcomes among pregnant and nonpregnant women admitted to the hospital for peptic ulcer disease (PUD). A retrospective matched cohort study was carried out using the Healthcare Cost and Utilization Project - National Inpatient Sample from 1999 to 2015. A cohort of pregnant women with PUD was generated and compared with an age-matched cohort of nonpregnant women with PUD at a 1:5 ratio. Conditional logistic regression analyses were used to evaluate the adjusted effect of PUD on variables and outcomes of interest, including associated conditions, management and treatment types, and complications. PUD was diagnosed in 2535 pregnant women and 12,675 age-matched nonpregnant women during the 16-year study period. As compared with nonpregnant women, pregnant women with PUD were less likely to undergo diagnostic or therapeutic esophagogastroduodenoscopies (EGD) for this indication. Outcomes including fever, infection, sepsis, shock, and transfusion were less likely to occur in pregnant women as compared to nonpregnant women. Pregnant women also experienced shorter hospital stays. Pregnant women who underwent EGD were more likely to experience a venous thromboembolism than nonpregnant women. Pregnant women with PUD are less likely to undergo interventional diagnostic and therapeutic procedures than nonpregnant women with PUD. The reluctance to intervene in pregnancy does not appear to result in more adverse PUD-associated outcomes.


Traceless chelation-controlled rhodium-catalyzed intermolecular alkene and alkyne hydroacylation.
A new functional-group tolerant, rhodium-catalyzed, sulfide-reduction process is combined with rhodium-catalyzed chelation-controlled hydroacylation reactions to give a traceless hydroacylation protocol. Aryl- and alkenyl aldehydes can be combined with both alkenes, alkynes and allenes to give traceless products in high yields. A preliminary mechanistic proposal is also presented.


Two signal transduction pathways involved in the catecholaminergic differentiation of avian neural crest-derived cells in vitro.
Molecules derived from the neural tube and found in chick embryo extract (CEE) and bone morphogenetic proteins (BMP) support the differentiation of neural crest-derived catecholaminergic (CA) neurons. We now report that intracellular signaling resulting in the activation of Map kinase (MapK) or translocation of Smad1 mediate the differentiation of CA neurons in response to CEE or BMP 4, respectively. The differentiation of CA neurons was significantly reduced by inhibiting MapK using PD98059 or by pan-specific blockade of tyrosine kinases using Herbimycin A. In the presence of BMP 4 and inhibitors of MapK signaling, differentiation of CA neurons was only moderately reduced. Independent of MapK, BMP 4 induced translocation of Smad1 from the cytosol to the nucleus and induced transcription of dHAND, a DNA binding protein required for the differentiation of CA neurons. The data suggest that CEE-derived factors and BMP4 support the differentiation of CA neurons via independent signaling pathways.


Pharmacokinetic Drug Interaction Study of Bazedoxifene and Ibuprofen.
The purpose of this article was to evaluate the potential for a pharmacokinetic interaction between bazedoxifene and ibuprofen. In a randomized crossover study, 12 healthy postmenopausal women (aged 45-65 years) received either a single oral dose of ibuprofen (600-mg tablet), bazedoxifene (20-mg capsule), or both ibuprofen and bazedoxifene during the 3 treatment periods. Serial blood samples were collected for pharmacokinetic analyses. There was no relationship between the UGT1A1 genotype and bazedoxifene clearance. The 90% log-transformed confidence intervals (CIs) for bazedoxifene Cmax , 96% to 144%, and AUC, 85% to 134%, were slightly above the bioequivalence limits of 80% to 125%. The 90% log-transformed CIs for ibuprofen pharmacokinetic parameters were within these limits (Cmax , 92%-122%; AUC, 94%-106%). The increase in bazedoxifene plasma concentrations when combined with ibuprofen versus bazedoxifene alone is unlikely to be clinically significant. The lack of interaction between bazedoxifene and ibuprofen suggests that they may be coadministered without dose adjustment.


Lateral alveolar ridge augmentation using a synthetic nano-crystalline hydroxyapatite bone substitution material (Ostim): preliminary clinical and histological results.
The purpose of this preliminary two-center clinical prospective study was to evaluate the tissue composition of augmented sites after the use of a nano-crystalline hydroxyapatite (ncHA) bone substitution material by clinical and histological examinations. A synthetic ncHA augmentation material was used without any additives in 14 patients requiring lateral ridge augmentation 6-7 months before (10 patients) or at implant placement (four patients). The ncHA material was covered by a titanium mesh for space maintenance. Clinical and radiographic parameters were evaluated and bone biopsy cores, obtained 6-7 months following augmentation, were assessed histologically and histomorphometrically. One patient showed gingival swelling, redness and pain at the augmentation site requiring removal of the titanium mesh 6 weeks postoperatively. In seven patients, a premature exposure of the titanium mesh without any inflammatory symptoms was noted. The width of the fixed gingival and the alveolar ridge height did not change significantly at least 6 months following augmentation (P>0.5), whereas a significant gain in alveolar ridge width (P=0.01) was noted. After a median period of prosthetic loading of 24 months, no implant was considered to be a failure. Histology revealed ncHA remnants in peripheral and central parts of biopsy cores obtained from seven patients after at least 6 months without histological symptoms of inflammation, whereas histomorphometry of bone cores revealed no significant differences of the mean percentage area of ncHA in peripheral (23.4%) and central (15.1%) parts of biopsy cores (P=0.262). The mean percentage area of bone colonizing the defect was 52.3%. Small amounts of ncHA were found after at least 6 months in bone biopsies. The former defect space was filled with bone. The alveolar ridge width gain was found to be significant after lateral augmentation utilizing ncHA, providing a quantitatively and qualitatively sufficient site for primary stable implant placement.


Modulation of calcineurin activity in mouse brain by chronic oral administration of cyclosporine A.
Calcineurin (CN) is an important phosphatase that mediates many physiological and pathological processes. The regulators of calcineurin (RCAN1) and Cu, Zn superoxide dismutase (SOD1) are two endogenous modulators of CN activity. Cyclosporine A (CsA) is a well-known exogenous inhibitor of CN and used as an immunosuppressive drug after transplantation and for the treatment of immune diseases. The degree of CN inhibition by CsA varies among each tissue. The brain accumulates low levels of CsA due to the blood-brain barrier after oral administration. In our study, we investigated RCAN1 and SOD1 expression in long-term CsA-treated mouse brain. Using Western blot, we found that chronic CsA treatment had caused significant up-regulation of RCAN1-1L and RCAN1-4 protein isoforms after 25 days in mouse brain. At the same time, chronic CsA treatment also resulted in decreased expression of SOD1. We simultaneously found more dramatic CN inhibition in mouse brain. It was suspected that the significant reduction of CN activity in vivo resulted partially from up-regulated RCAN1 and down-regulated SOD1 expression. In contrast, CsA treatment in SY5Y cells affected SOD1 expression and CN activity significantly, but had no obvious effects on RCAN1-1 mRNA expression. The changes of RCAN1, SOD1, and CN activity may be part of maladaptive responses, resulting in neuropathological conditions. These data might partially explain CsA neurotoxicity despite the low concentration of CsA in brain.


The effect of osteoarthritis of the knee on the biomechanics of other joints in the lower limbs.
The aim of this study was to examine the loading of the other joints of the lower limb in patients with unilateral osteoarthritis (OA) of the knee. We recruited 20 patients with no other symptoms or deformity in the lower limbs from a consecutive cohort of patients awaiting knee replacement. Gait analysis and electromyographic recordings were performed to determine moments at both knees and hips, and contraction patterns in the medial and lateral quadriceps and hamstrings bilaterally. The speed of gait was reduced in the group with OA compared with the controls, but there were only minor differences in stance times between the limbs. Patients with OA of the knee had significant increases in adduction moment impulse at both knees and the contralateral hip (adjusted p-values: affected knee: p < 0.01, unaffected knee p = 0.048, contralateral hip p = 0.03), and significantly increased muscular co-contraction bilaterally compared with controls (all comparisons for co-contraction, p < 0.01). The other major weight-bearing joints are at risk from abnormal biomechanics in patients with unilateral OA of the knee.


Structure-function studies of two novel UDP-GlcNAc C6 dehydratases/C4 reductases. Variation from the SYK dogma.
Two subfamilies of UDP-GlcNAc C6 dehydratases were recently identified. FlaA1, a short soluble protein that exhibits a typical SYK catalytic triad, characterizes one of these subfamilies, and WbpM, a large membrane protein that harbors an altered SMK triad that was not predicted to sustain activity, represents the other subfamily. This study focuses on investigating the structure and function of these C6 dehydratases and the role of the altered triad as well as additional amino acid residues involved in catalysis. The significant activity retained by the FlaA1 Y141M triad mutant and the low activity of the WbpM M438Y mutant indicated that the methionine residue was involved in catalysis. A Glu(589) residue, which is conserved only within the large homologues, was shown to be essential for activity in WbpM. Introduction of this residue in FlaA1 enhanced the activity of the corresponding V266E mutant. Hence, this glutamate residue might be responsible for the retention of catalytic efficiency in the large homologues despite alteration of their catalytic triad. Mutations of residues specific for the short homologues (Asp(70), Asp(149)-Lys(150), Cys(103)) abolished the activity of FlaA1. Among them, C103M prevented dimerization but did not significantly affect the secondary structure. The fact that we could identify subfamily-specific residues that are essential for catalysis suggested an independent evolution for each subfamily of C6 dehydratases. Finally, the loss of activity of the FlaA1 G20A mutant provided evidence that a cofactor is involved in catalysis, and kinetic study of the FlaA1 H86A mutant revealed that this conserved histidine is involved in substrate binding. None of the mutations investigated altered the substrate, product, and function specificity of these enzymes.


[Clinical management of the patient affected with acute renal failure (ARF) secondary to volume depletion].
Most cases of ARF are secondary to volume depletion. In the literature, very few scientific publications address the problem of what to do when confronted with such a patient. As regarding the diagnosis of hypovolemia, an accurate history and physical examination can help to determine both the presence and etiology of volume depletion; postural hypotension (decrement in systolic blood pressure of more than 20 mmHg after standing from the supine position), associated with a pulse increment of 30 beats/min or more and dizziness are specific symptoms of hypovolemia. Laboratory indices are useful to diagnose volume depletion, but their interpretation is not simple, and they may not be available in the non-nephrologic environment. Fluid replacement therapy in hypovolemia is largely dependent upon the type of fluid that has been lost and concurrent electrolytic and acid-base disorders. Patients with hypernatremia and volume depletion should receive mild hypotonic solutions, whereas those with hyponatremia and hypovolemia should receive mild hypertonic solutions. The entity of reinfusion depends on daily losses. Conversely, monitoring of body weight can be considered an adequate index of fluid balance. Concerning the treatment of ARF, the use of loop diuretics in the early phases of pre-renal ARF decrease oxygen consumption in the tubular cells by inhibiting transcellular sodium transport, therefore preventing or limiting ischemic cell injury. The use of loop diuretics should also be evaluated in intermediate syndrome and ischemic NTA where diuretics can, respectively, reduce renal ischemia and convert oliguric ARF into the non-oliguric form.


Concentration of filaggrin monomers, its metabolites and corneocyte surface texture in individuals with a history of atopic dermatitis and controls.
Atopic dermatitis (AD) is characterized by skin barrier dysfunction. Notably, a high number of nano-scale protrusions on the surface of corneocytes, which can be expressed by the Dermal Texture Index (DTI), were recently associated with paediatric AD, loss-of-function mutations in filaggrin gene (FLG) and reduced levels of natural moisturizing factors (NMF). No study has so far examined the association between these parameters and monomeric filaggrin levels in adults. To determine DTI, monomeric filaggrin and NMF in healthy controls and a group of patients with controlled dermatitis. A total of 67 adults (20 healthy controls and 47 dermatitis patients) were included. In the patient population, a personal history of AD was diagnosed by the U.K. Working Party's Diagnostic Criteria. All participants were tested for FLG mutations (R501X, 2282del4, R2447X). Transepidermal water loss, monomeric filaggrin, DTI and NMF were measured. In the patient population, 78.7% (37/47) had a history of AD and 59.5% (28/47) had FLG mutations. Patients had significantly higher levels of DTI and significantly lower levels of monomeric filaggrin and NMF compared to the 20 healthy controls. Among patients, reduced level of monomeric filaggrin and NMF correlated with the presence of FLG mutations and clinical phenotypes such as xerosis, palmar hyperlinearity and AD. Among healthy controls, DTI was significantly higher in the oldest age group compared to the two younger age groups. A significant difference in DTI, monomeric filaggrin and NMF levels was found when comparing dermatitis patients with healthy controls. These findings suggest that even mild dermatitis or non-visible inflammation has a significant and negative effect on the skin barrier as inflammation is known to reduce filaggrin levels. DTI was significantly increased in aged individuals in the healthy control group, suggesting a gradual change in corneocyte morphology with age.


The feeding of beta-carotene down-regulates serum IgE levels and inhibits the type I allergic response in mice.
Feed containing beta-carotene was administered orally to BALB/c mice immunized intraperitoneally with ovalbumin (OVA) for approximately 1 month. The titers of OVA-specific IgE, OVA-specific IgG1 and OVA-specific IgG2a in the mouse sera were determined. The OVA-specific IgE titer and OVA-specific IgG1 titer by mice fed beta-carotene were significantly inhibited. On the other hand, the OVA-specific IgG2a titer in mice fed beta-carotene was significantly greater than those of control mice. The OVA-specific IgE suppression of beta-carotene feeding was dose-dependent. We also examined the effect of fed beta-carotene on active systemic anaphylaxis. Feeding beta-carotene to mice immunized with OVA inhibited the immediate reduction of the body temperature induced by antigen stimulation. Furthermore, the increase in serum histamine in the mice fed beta-carotene under active systemic anaphylaxis was lower than in controls. We then examined the pattern of cytokine production by spleen cells from mice followed by restimulation with OVA in vitro. The spleen cells from the mice fed beta-carotene produced more IFN-gamma, IL-12 and IL-2 than those from the control group. In contrast, the spleen cells from the mice fed beta-carotene produced less IL-4, IL-5, IL-6, IL-10 than those from the control group. Furthermore, analysis of IFN-gamma mRNA levels of the splenocytes using the real-time quantitative RT-PCR technique revealed higher levels in the splenocytes from the mice fed beta-carotene. These findings suggest that feeding beta-carotene improves the helper T cell (T(H))1-T(H)2 balance, inhibiting specific IgE and IgG1 production and antigen-induced anaphylactic response.


Trafficking of HIV-1 RNA is mediated by heterogeneous nuclear ribonucleoprotein A2 expression and impacts on viral assembly.
Few details are known about how the human immunodeficiency virus type 1 (HIV-1) genomic RNA is trafficked in the cytoplasm. Part of this process is controlled by the activity of heterogeneous nuclear ribonucleoprotein A2 (hnRNP A2). The role of hnRNP A2 during the expression of a bona fide provirus in HeLa cells is investigated in this study. Using immunofluorescence and fluorescence in situ hybridization techniques, we show that knockdown of hnRNP A2 expression in HIV-1-expressing cells results in the rapid accumulation of HIV-1 genomic RNA in a distinct, cytoplasmic space that corresponds to the microtubule-organizing center (MTOC). The RNA exits in the nucleus and accumulates at the MTOC region as a result of hnRNP A2 knockdown even during the expression of a provirus harboring mutations in the hnRNP A2-response element (A2RE), the expression of which results in nuclear retention of genomic RNA. We also demonstrate that hnRNP A2 expression is required for downstream trafficking of genomic RNA from the MTOC in the cytoplasm. Genomic RNA localization at the MTOC that was both the result of hnRNP A2 knockdown and the overexpression of Rab7-interacting lysosomal protein had little effect on pr55Gag synthesis but negatively influenced virus production and infectivity. These data indicate that altered HIV-1 genomic RNA localization modulates viral assembly and that the MTOC serves as a central site to which HIV-1 genomic RNA converges following its exit from the nucleus, with the host protein, hnRNP A2, playing a central role in taking it to and from this site in the cell.


Gray Matter Volume in Elderly adults With ADHD: Associations of Symptoms and Comorbidities With Brain Structures.
Objective: To investigate total and selected region-of-interest-based gray matter volume (GMV) in older adults with ADHD. Method: Twenty-five elderly (≥65 years old) patients with ADHD and 34 healthy controls underwent 1.5-T magnetic resonance imaging (MRI). We used voxel-based morphometry to compare GMV between groups and performed a correlation analysis with ADHD symptoms and comorbidities. Results: Findings revealed a smaller total GMV in males with ADHD and a smaller GMV in the right medial frontal orbital area extending toward the medial frontal superior, the frontal superior, and the subgenual anterior cingulate cortex (ACC) besides correlations between inattentiveness and ACC (bilaterally) and left cerebellum, hyperactivity/impulsivity and the left frontal inferior orbital, depression and caudate (bilaterally), and the right inferior parietal lobule. Conclusion: Neural correlates in regions related to attention, executive control, and affective processing suggest that impairments in frontostriatal and frontoparietal-cerebellar areas observed in adults with ADHD persist into old age.


Characterization and Discrimination of Volatile Compounds in Chilled Tan Mutton Meat during Storage Using HiSorb-TD-GC-MS and E-Nose.
Chilled Tan mutton is currently the mainstream of Tan mutton production and consumption in China, but the reports on chilled meat quality evaluation and shelf-life discrimination by volatiles are limited. This study aimed to investigate the changes of volatile compounds in chilled Tan mutton at four storage stages (1d, 3d, 5d, 7d) in order to differentiate the various storage stages. An analysis protocol was established for the characterization and discrimination of the volatiles in chilled Tan mutton based on high capacity sorptive extraction-thermal desorption-gas coupled with chromatography-mass spectrometry (HiSorb-TD-GC-MS), electronic nose (E-nose), and multivariate statistical analysis. A total of 96 volatile compounds were identified by HiSorb-TD-GC-MS, in which six compounds with relative odor activity value >1 were screened as the key characteristic volatiles in chilled Tan mutton. Four storage stages were discriminated by partial least squares discriminant analysis, and nine differential volatile compounds showed a variable importance for the projection score >1, including octanoic acid, methyl ester, decanoic acid, methyl ester, acetic acid, heptanoic acid, methyl ester, propanoic acid, 2-hydroxy-, methyl ester, (ñ)-, hexanoic acid, propanoic acid, butanoic acid, and nonanoic acid. With the volcano plot analysis, hexadecanoic acid, methyl ester, was the common volatile marker candidate to discriminate chilled stages of Tan mutton. Meanwhile, E-nose could discriminate chilled Tan mutton at different storage stages rapidly and efficiently using linear discriminant analysis. Furthermore, E-nose sensors could obtain comprehensive volatile profile information, especially in esters, acids, and alcohols, which could confirm the potential of E-nose for meat odor recognition. Thus, this analysis protocol could characterize and discriminate the volatiles in chilled Tan mutton during storage.


Accuracy of ultrasound in diagnosing abdominal masses.
B-mode ultrasonography was performed in 246 patients with suspected abdominal masses over a seven-year period. In 105 (40 percent), the accuracy of ultrasonic diagnosis was evaluated surgically. Sonography was proven correct in 60 (57 percent) patients who had undergone operation. Among 141 patients who had not undergone operation and whose diagnoses were established by other means, ultrasonography agreed with the clinical diagnosis in 69 (31 percent). Ultrasound accuracy, as confirmed by operation, was highest for splenic masses (100 percent) and for aortic aneurysm (88 percent). Liver masses were correctly identified in 56 percent of patients and gallbladder lesions in 38 percent. While only a 48 percent accuracy was obtained in diagnosing pancreatic disease, 64 percent of all pseudocysts were localized. Ultrasonography correlated positively with operative findings in 56 percent of renal masses. Intraperitoneal abscess was accurately diagnosed in 61 percent of patients but retroperitoneal adenopathy in only 33 percent. Abdominal ultrasonography, while accurately diagnosing splenic and aortic masses, failed to identify approximately half of other mass lesions. Improved techniques hold promise of improving this diagnostic accuracy.


Films of Poly(Hydroxybutyrate) (PHB) and Copper with Antibacterial Activity.
Poly(3-hydroxybutyrate), PHB, is a hydrophobic biopolymer with good mechanical and barrier properties. However, neat PHB is a semicrystalline polymer with a relative high degree of crystallinity and poor film properties. In this work, this biopolymer was plasticized with glycerol tributyrate and functionalized with copper (II) sulfate, allowing us to obtain biodegradable antimicrobial flexible films. Films with the minimum inhibitory concentration (MIC) of copper (II) sulfate presented a higher roughness than neat PHB films. The presence of plasticizer significantly improved the copper sulfate diffusion process, which was evidenced by a greater inhibition halo for plasticized materials compared to unplasticized ones, at the same salt concentration. Plasticized PHB with 2.5% copper (II) sulfate inhibited both Gram-positive (Staphylococcus aureus) and Gram-negative (Pseudomona aeruginosa) bacteria, as determined by the bacterial inhibition halo. In addition, neat PHB films and PHB containing copper (II) sulfate did not show in vitro cytotoxicity in the L-929 cell line. Thus, plasticized PHB functionalized with copper (II) sulfate can be used as biodegradable antimicrobial flexible films for different applications.