Voltage-dependent clamp of intracellular pH of identified leech glial cells.
1. The intracellular pH (pHi) was measured in voltage-clamped, giant neuropile glial cells in isolated segmental ganglia of the leech Hirudo medicinalis, using double-barrelled, pH-sensitive microelectrodes and a slow, two-electrode voltage-clamp system. The potential sensitivity of the pHi regulation in these glial cells was found to be due to an electrogenic Na(+)-HCO3- cotransporter (Deitmer & Szatkowski, 1990). 2. In the presence of 5% CO2 and 24 mM HCO3- (pH 7.4), pHi shifted by 1 pH unit per 110 mV, corresponding to a stoichiometry of 2HCO3-: 1 Na+ of the cotransporter, while in Hepes-buffered CO2-HCO3(-)-free saline (pH 7.4), pHi changed by 1 pH unit per 274 mV. The potential sensitivity of pHi decreased at lower pHo, being 1 pH unit per 216 mV at external pH (pHo) 7.0. 3. Changing pHo between 7.8 and 6.6 induced pHi shifts with a slope of 0.72 pHi units per pHo unit in non-clamped, and of 0.80 pHi units per pHo unit in voltage-clamped cells, indicating that pHi largely followed pHo. The electrochemical gradient of H(+)-HCO3- across the glial membrane was around 56 mV, and remained almost constant over this pHo range. 4. The membrane potential-dependent and pHo-sensitive shifts of pHi were unaffected by amiloride, an inhibitor of Na(+)-H+ exchange. 5. The intracellular acidification upon lowering pHo could be reversed by depolarizing the membrane as predicted from a cotransporter, whose equilibrium follows the membrane potential by resetting pHi. 6. The results indicate that the pHi of leech glial cells is dominated by the electrogenic Na(+)-HCO3- cotransporter, and is hence a function of the membrane potential, and the Na+ and H(+)-HCO3- gradients, across the cell membrane.


Post-thinning using Ar ion-milling system for transmission electron microscopy specimens prepared by focused ion beam system.
We investigate Ar ion-milling rates and Ga-ion induced damage on sample surfaces of Si and GaAs single crystals prepared by focused ion beam (FIB) method for transmission electron microscopy observation. The convergent beam electron diffraction technique with Bloch simulation is used to measure the thickness of the Ar-ion milled samples to calculate the milling rates of Si and GaAs single crystals. The measurement shows that an amorphous layer is formed on the sample surface and can be removed by further Ar-ion milling. In addition, the local symmetry breaking induced by FIB is investigated using quantitative symmetry measurement. The FIBed-GaAs sample shows local symmetry breaking after FIB milling, although the FIBed-Si sample has no considerable symmetry breaking.


Sustaining and expanding systems of care to provide mental health services for children, youth and families across America.
The Substance Abuse and Mental Health Services Administration has been instrumental in supporting the development and implementation of systems of care to provide services to children and youth with serious mental health conditions and their families. Since 1993, 173 grants have been awarded to communities in all 50 states, Puerto Rico, Guam, the District of Columbia, and 21 American Indian/Alaska Native communities. The system of care principles of creating comprehensive, individualized services, family-driven and youth-guided care and cultural and linguistic competence, supported by a well-trained and competent workforce, have been successful in transforming the field of children's mental health and facilitating the integration of child-serving systems. This approach has achieved positive outcomes at the child and family, practice and system levels, and numerous articles have been published using data collected from system of care communities, demonstrating the effectiveness of this framework. This article will describe lessons learned from implementing the system of care approach, and will discuss the importance of expanding and sustaining systems of care across the country.


A 31-Year-Old Man With Asthma, Chest Discomfort, and Shortness of Breath.
A 31-year-old man with a medical history of well-controlled asthma presented with a 3-week history of midsternal chest pressure and shortness of breath. His symptoms were associated with malaise, weakness, 40-pound weight loss over several months, and intermittent fever up to 38.3ºC. A week and half earlier, he started experiencing a productive cough with white sputum and arthralgias in his knees. He denied any exacerbating or relieving factors for his symptoms. Additionally, he had a pruritic rash on his thighs for the last year that remained unresolved despite antifungal medication.


Theory and Practice of Compression Therapy for Treating and Preventing Venous Ulcers.
Compression therapy is the basis for treating the cause of venous ulcers and preventing recurrence. Various systems are currently available for applying compression and adapting them to patients' needs can improve adherence to treatment. Understanding the principles that underlie compression therapy is essential for success. Although this paper focuses mainly on venous ulcers, compression has also proven beneficial for other conditions, such as lymphedema and wounds resulting from injury or inflammation.


Polymeric behavior evaluation of PVP K30-poloxamer binary carrier for solid dispersed nisoldipine by experimental design.
High melting point polymeric carrier without plasticizer is unacceptable for solid dispersion (SD) by melting method. Combined polymer-plasticizer carrier significantly affects drug solubility and tableting property of SD. To evaluate and optimize the combined effect of a binary carrier consisting PVP K30 and poloxamer 188, on nisoldipine solubility and tensile strength of amorphous SD compact (SDcompact) by experimental design. SD of nisoldpine (SDnisol) was prepared by melt mixing with different PVP K30 and poloxamer amount. A 32 factorial design was employed using nisoldipine solubility and tensile strength of SDcompact as response variables. Statistical optimization by design expert software, and SDnisol characterization using ATR FTIR, DSC and microscopy were done. PVP K30:poloxamer, at a ratio of 3.73:6.63, was selected as the optimized combination of binary polymeric carrier resulting nisoldipine solubility of 115 μg/mL and tensile strength of 1.19 N/m2. PVP K30 had significant positive effect on both responses. Increase in poloxamer concentration after a certain level decreased nisoldipine solubility and tensile strength of SDcompact. An optimized PVP K30-poloxamer binary composition for SD carrier was developed. Tensile strength of SDcompact can be considered as a response for experimental design to optimize SD.


Implementation of an evidence-based depression care management program (PEARLS): perspectives from staff and former clients.
Although researchers develop evidence-based programs for public health practice, rates of adoption and implementation are often low. This qualitative study aimed to better understand implementation of the Program to Encourage Active, Rewarding Lives for Seniors (PEARLS), a depression care management program at a Seattle-King County area agency on aging. We used stratified, purposive sampling in 2008 to identify 38 PEARLS clients and agency staff for participation. In 9 focus groups and 1 one-on-one interview, we asked participants to identify benefits and negative consequences of PEARLS, facilitators of and barriers to program implementation, and strategies for overcoming the barriers. Two independent researchers used thematic analysis to categorize data into key themes and subthemes. PEARLS benefits clients by decreasing depression symptoms and addressing other concerns, such as health problems. For staff, PEARLS provides "another set of eyes" and is a comprehensive program to help them meet clients' mental health needs. Barriers included issues with implementation process (eg, lack of communication) and the perception that eligibility criteria were more rigid than those of other agency programs. Recommended solutions included changing eligibility criteria, providing additional staff training, increasing communication, and clarifying referral procedures, roles, and responsibilities. Barriers to PEARLS delivery discourage referrals to what is generally viewed as a beneficial program. Implementing participants' strategies for overcoming these barriers can enhance delivery of PEARLS to a greater number of older adults and help them improve their depression symptoms.


A self-directed co-creation process for developing a care pathway for patients on oral anticancer therapy: A qualitative process evaluation.
To provide in-depth insight in stakeholders' experiences with the self-directed co-creation of a care pathway for patients treated with oral anticancer drugs, and to identify influencing factors for the success of the co-creation process that are persistent throughout the prior pilot phase and the scale-up phase. This qualitative process evaluation was performed in 11 Belgian oncology departments participating in a scale-up project. Semi-structured interviews with local coordinators (n = 13) and members of the project teams (n = 19), responsible for the co-creation of the care pathway, were conducted. Data were thematically analyzed. Despite the external support (including group-level coaching and the use of well-defined supportive tools) to promote self-directedness, the co-creation process was perceived burdensome. Three influencing factors were persistent throughout the pilot and scale-up phase: a) shared leadership among the coordinator, physician and hospital management, b) an intrinsically motivated team driven by additional extrinsic factors, and c) a balance between external support and self-directedness. This study shows that the self-directed co-creation of a care pathway is feasible on the condition that important prerequisites are met, including shared leadership and team motivation. More concrete tools, such as a model care pathway, seem needed to increase feasibility of the self-directed co-creation of the care pathway. Yet, these tools should allow tailoring to the specific hospital context. The findings of this study can be useful for further scale-up to other oncology centers, but can also be extrapolated to other healthcare settings.


Advancing a Systemic Perspective on Multidisciplinary Teams: A Comparative Case Study of Work Organisation in Four Multiple Sclerosis Hospitals.
Many care organisations claim to employ multidisciplinary teams, but the term is used to describe quite different forms of collaboration. A systemic view of the work organisation of care delivery is presented and applied in this article that allows to identify and understand often overlooked yet important differences regarding team composition, working relationships and therapeutic relationships. We used modern socio-technical systems theory to study care delivery for a particular patient population as a system of interrelated activities. The concept of work organisation refers to the way in which the composite task of care delivery is divided into distinct tasks and how these are grouped in either monodisciplinary or multidisciplinary organisational units. The systemic perspective was applied in a comparative case study of four Multiple Sclerosis hospitals. Among the hospitals, one was characterised by a functional work organisation, with similar tasks grouped in monodisciplinary teams. Cross-disciplinary working and therapeutic relationships were established on an ad hoc basis. The three other hospitals adopted a more process-oriented work organisation (which groups all tasks related to a specific care process within a single, multidisciplinary team). The more process-oriented the work organisation, the more working relationships and therapeutic relationships appeared to be fixed and continuous. The systemic view adopted in this study yields a better understanding of multidisciplinary teams through the concept of work organisation. The actual composition of multidisciplinary teams, and the related working and therapeutic relationships will vary depending on the type of underlying work organisation. Further validation of this conclusion will be needed in other settings.


Periarticular injection and hamstring block versus placebo for pain control in anterior cruciate ligament reconstruction: A randomized controlled trial.
To study the effectiveness of periarticular infiltration (PI), including the proximal donor site vs. placebo in anterior cruciate ligament (ACL) reconstruction. A total of 44 patients were randomized in two groups assigned to receive PI or placebo. The perioperative protocol was the same for both groups. The principal outcome was pain measured at 8 and 24 h by a visual analog scale (VAS). The pain was registered in the knee and the proximal donor site. Pain scores were also assessed to determine whether the VAS improvement would reach the threshold values reported for the minimal clinically significant difference. The secondary outcome was the need for opioid rescue medication. Patients receiving PI exhibited lower pain values in the knee at 8 h (mean PI 35.00 ± 5.76 vs. placebo 60.23 ± 4.52 p = 0.01) and at 24 h (mean PI 37.23 ± 5.62 vs. placebo 55.55 ± 3.41 p = 0.008). These results were above the threshold for clinical significance. No improvements were found in proximal donor site pain and consumption of opioid rescue medication. Complications were comparable between the two groups. PI significantly reduced pain in the knee vs. placebo after ACL reconstruction with hamstring autograft at 8 and 24 h after surgery. The instillation of part of the mixture in the proximal hamstring stump did not result in any improvement LEVEL OF EVIDENCE I: Level I, randomized controlled trial.


The long-run effects of financial development on income inequality: Evidence from the Asia-Pacific countries.
Income inequality is a vexing developmental challenge for governments and policymakers as it impedes social transformation and economic growth and development. Meanwhile, promoting financial development is generally regarded as an effective way to achieve inclusive and sustainable growth. This study examines the long-run effects of financial development, economic growth, and their combined effects on income inequality for 12 Asia-Pacific countries from 1990 to 2021. This paper employs various econometric techniques and different financial development proxies to ensure the findings' robustness. The paper also constructs a financial development index using the principal component analysis to fully capture the comprehensive effect of financial development on income inequality. Empirical results reveal that the impact of financial development on income inequality follows the inverted U-shaped relationship - financial development widens income inequality and only reduces income when surpassing its turning point. Findings further reveal that the nonlinear effect of financial development on income inequality is contingent upon the level of per capita income. Thus, policies promoting financial development to reduce income inequality should consider the existing level of per capita income.


Exploring the potential of paper-based electrokinetic phenomena in PoC biosensing.
In order to decentralize health care, the development of point-of-care (PoC) assays has gained significant attention in recent decades. The lateral flow immunoassay (LFIA) has emerged as a promising bioanalytical method due to its low cost and single-step detection process. However, its limited sensitivity and inability to detect disease biomarkers at clinically relevant levels have hindered its application for early diagnosis. This review explores the potential of merging different electrokinetic phenomena into paper-based assays to enhance their analytical performance, offering a versatile and affordable approach for PoC testing. The review exposes the challenges faced in integrating electrokinetic phenomena with paper-based biosensing and concludes by discussing the issues that need to be improved to maximize the potential of this technology for early diagnosis.


Coercion and procedural justice in psychiatric care: state of the science and implications for nursing.
Coercive treatment regimens have increased in variety and intensity over the past decade and include such options as outpatient commitment (OPC) and mental health courts. The intimate involvement of nurses in coerced treatment situations in both inpatient and outpatient settings necessitates a closer examination of its effects. OPC presumably offers greater flexibility and freedom for consumers than lengthy inpatient stays but also extends the state's control over their lives beyond the institution. Although OPC has been shown to decrease rates of rehospitalization and violence, it also is associated with increased levels of perceived coercion. The relationship of the perception of coercion to treatment outcomes is complex and not clearly understood. The goal of OPC is treatment adherence and ultimately increased quality of life, but research has produced conflicting results in those areas. Numerous episodes of OPC may have a cumulative effect on the perception of coercion and contribute to treatment avoidance. However, there is evidence that the perception of coercion can be mitigated by procedural justice that is demonstrated by fairness, patient inclusion in the process, and benevolence on the part of authority figures. Implications for nursing practice and research concerning coercion, procedural justice, and OPC are discussed.


Measuring the cardiac output in acute emergency admissions: use of the non-invasive ultrasonic cardiac output monitor (USCOM) with determination of the learning curve and inter-rater reliability.
Traditionally, assessment of the cardiac output has been limited to theatre or the intensive care unit. However, non-invasive cardiac output estimation is now readily available, and its application may have wider benefit in the emergency setting. The non-invasive ultrasonic cardiac output monitor (USCOM) was investigated to determine its learning curve and inter-rater reliability. Four trainee operators each performed stroke volume measurements on 25 volunteers, compared to an experienced operator pre- and post-passive leg raise. Inter-rater reliability was then assessed on 24 acute emergency in-patients. Mean percentage difference in stroke volume decreased from 19% (95% confidence intervals 14-23) across volunteers 1-5, to 6% (4-8) for the last 5 volunteers scanned. Consequently, on acute emergency in-patients, excellent inter-rater reliability (Lin's concordance correlation coefficient (ρc) 0.96 (0.92-0.98)) and agreement of a change ≥10% in stroke volume following passive leg raise on 23/24 cases were found. Following a training period of less than 5 h, USCOM stroke volume measurements demonstrated excellent inter-rater reliability.


Therapeutic plasma exchange and intravenous immune globulin in the treatment of heparin-induced thrombocytopenia: A systematic review.
Immunomodulatory strategies in heparin-induced thrombocytopenia (HIT) include the use of intravenous immune globulin (IVIG) and therapeutic plasma exchange (TPE). The optimal application of these therapies is unknown and outcomes data are limited. We investigated treatment categories and laboratory and clinical outcomes of IVIG and/or TPE in HIT with a systematic literature review. We searched MEDLINE, Embase, and Web of Science through December 2019 for studies combining controlled vocabulary and keywords related to thrombocytopenia, heparin, TPE, and IVIG. The primary outcome was treatment indication. Secondary outcomes were platelet recovery, HIT laboratory parameters, heparin re-exposure, and post-treatment course. Case-level data were analyzed by qualitative synthesis. After 4241 references were screened, we identified 60 studies with four main categories of IVIG and/or TPE use as follows: (a) treatment of refractory HIT (n = 35; 31%); (b) initial therapy (n = 45; 40%); (c) cardiopulmonary bypass surgery (CPB; n = 30; 27%); and (d) other (n = 2; 2%). IVIG was most commonly used for the treatment of refractory HIT while TPE was primarily used to facilitate heparin exposure during CPB. Both IVIG and TPE were equally used as initial therapy. Heparin re-exposure occurred without thrombotic event in 29 TPE-treated patients and three IVIG-treated patients. In patients with HIT, both TPE and IVIG are used for initial therapy or treatment of refractory HIT. However, TPE is more commonly used in patients undergoing CPB. Prospective studies may help clarify which treatment is indicated in HIT population subsets.


Interaction centres of purine nucleotides: adenosine-5'-diphosphate and adenosine-5'-triphosphate in their reactions with tetramines and Cu(II) ions.
The interactions between the nucleotides: adenosine-5'-diphosphate (ADP) and adenosine-5'-triphosphate (ATP) with spermine (Spm) and 1,11-diamine-4,8-diazaundecane (3,3,3-tet), as well as Cu(II) ions are studied. In the metal-free systems nucleotide-polyamine molecular complexes have been found to form, in which the interaction centres are the nitrogen atoms of the purine ring N(1) and N(7), oxygen atoms of the phosphate group of the nucleotide (for 3,3,3-tet) and protonated nitrogen atoms of the polyamine. Significant differences in the mode of metallation between the systems with Spm and 3,3,3-tet have been established. In the systems with Spm, the main products are protonated species with [N(7),O] chromophore and the nitrogen N(1) is involved in the intramolecular interaction additionally stabilising the complex. In the systems with 3,3,3-tet the formation of metal-ligand-ligand (MLL) species has been observed, in which the oxygen atoms from the phosphate group and the nitrogen atoms from the polyamine are involved in the metallation, while the N(1) and N(7) atoms from the purine ring of the nucleotide remain outside the inner coordination sphere of the copper ion. The main centre of metallation in the nucleotide, both with Spm and 3,3,3-tet, is the phosphate group of the nucleotide.


Measuring development of a child's early walking: implications for clinical assessment of gait.
This study examined the three-dimensional kinematics and motor development patterns in early walking gait longitudinally over 8 mo. and presents an example of walking development of one normal child which might be used for comparative purposes in the clinical assessment of gait.


Drug effects on the intestinal absorption of estrogens.
It is now recognized that intestinal metabolism is one of the major factors affecting the bioavailability of orally administered, natural and synthetic estrogens. Other drugs and dietary constituents taken concomitantly may modify the intestinal metabolism and enterohepatic circulation of these steroids. Various antibiotics, phenobarbitone and large doses of ascorbic acid have been reported to modify the clinical efficacy of steroidal oral contraceptives. Experimental and other evidence indicate that antibiotics, by modifying the intestinal microflora, affect the intestinal metabolism and enterohepatic circulation of estrogens. Phenobarbitone and ascorbic acid on the other hand probably influence intestinal metabolism through an effect on intestinal mucosal enzymes. Further experimental evidence in rats suggest that such commonly used drugs as analgesic acetylsalicylic acid, antimalarial chloroquine phosphate and alcohol also alter the intestinal mucosal metabolism of estradiol and estrone sulphate and may thus alter the bioavailability of these estrogens. Further studies are necessary to evaluate the clinical significance of these observations.


Changes in contributions of age- and cause-specific mortality to the widening life expectancy gap between North and South Korea, 1990-2019: An analysis of the Global Burden of Disease Study 2019.
Life expectancy gaps between North and South Korea have increased but contributions to these gaps remain poorly understood. Using data from the Global Burden of Disease Study (GBD) 2019, we examined how much death from specific diseases contributed to these gaps in different age groups over three decades. Data for death numbers and population by sex and 5-year age groups in both North and South Korea from 1990 to 2019 were extracted from the GBD 2019 to calculate life expectancy. Joinpoint regression analysis was conducted to investigate changes in life expectancy in North and South Korea. We used decomposition analysis to partition differences in life expectancy within and between the two Koreas into changes in age- and cause-specific death contributions. Life expectancy increased in two Koreas from 1990 to 2019, but North Korea experienced a marked decline in life expectancy during the mid-1990s. The life expectancy gaps between the two Koreas were greatest in 1999, with a difference of 13.3 years for males and 14.9 years for females. The main contributors to these gaps were higher under-5 mortality from nutritional deficiencies for males (4.62 years) and females (4.57 years) in North Korea, accounting for about 30% of the total gap in life expectancy. After 1999, the life expectancy gaps reduced but persisted with differences of about ten years by 2019. Notably, chronic diseases contributed to about 8 out of 10 years of life expectancy gap between the two Koreas in 2019. Differential cardiovascular disease mortality in the older groups was the main contributor to the life expectancy gap. The contributors to this gap have shifted from nutritional deficiencies in children younger than five years to cardiovascular disease among elderly people. Efforts for strengthening social and healthcare systems are needed to curb this large gap.


The Protein Maker: an automated system for high-throughput parallel purification.
The Protein Maker is an automated purification system developed by Emerald BioSystems for high-throughput parallel purification of proteins and antibodies. This instrument allows multiple load, wash and elution buffers to be used in parallel along independent lines for up to 24 individual samples. To demonstrate its utility, its use in the purification of five recombinant PB2 C-terminal domains from various subtypes of the influenza A virus is described. Three of these constructs crystallized and one diffracted X-rays to sufficient resolution for structure determination and deposition in the Protein Data Bank. Methods for screening lysis buffers for a cytochrome P450 from a pathogenic fungus prior to upscaling expression and purification are also described. The Protein Maker has become a valuable asset within the Seattle Structural Genomics Center for Infectious Disease (SSGCID) and hence is a potentially valuable tool for a variety of high-throughput protein-purification applications.


Primary sarcoma of the pulmonary trunk and/or right or left main pulmonary artery--a rare cause of obstruction to right ventricular outflow. Report on two patients and analysis of 35 previously described patients.
Clinical and morphologic observations are described in two women with primary sarcoma of the pulmonary trunk, and observations in 35 previously described patients with primary sarcoma involving a major extrapulmonary pulmonary artery are summarized. The neoplasm produces symptoms by causing obstruction to right ventricular outflow or by dislodging tumor fragments to the smaller intrapulmonary pulmonary arteries with or without pulmonary infarction. The sarcoma nearly always arises from the pulmonary trunk to which it is firmly attached. Although it grows to a large size within the lumen, it infrequently, despite its highly malignant histologic pattern, extends through the wall of the pulmonary trunk or metastasizes outside the pulmonary circulation. It may mimic a variety of more common disorders. Diagnosis can be achieved by angiography and treatment starts with total excision.


[Ureaplasma urealyticum infection affects sperm plasma membrane integrity in infertile men].
To determine the impact of Ureaplasma urealyticum (Uu) infection on the integrity of sperm plasma membrane in infertile males. Sixty-three semen samples were divided into a Uu infection group (n = 32) and a normal control group (n = 31). Conventional semen analyses were performed by computer-assisted semen analysis (CASA) and Uu detected by the culture method. The semen samples were washed with PBS and dyed by SYBR-14/PI double fluorescent staining, followed by detection of the integrity of sperm plasma membrane by flow cytometry. The percentage of the sperm with intact plasma membrane was indicated as the percentage of sperm emitting green fluorescence (SYBR-14+/PI-%). The Uu infection group showed a significantly decreased integrity of sperm plasma membrane ([45.14 +/- 10.69]%) and reduced percentage of grade a + b sperm ([23.29 +/- 8.81]%) as compared with the normal control group ([72.68 +/- 9.91]% and [46.32 +/- 9.54]%) (P < 0.01). But there were no significant differences in the semen volume, pH value, and sperm concentration between the two groups (P > 0.05). Uu infection decreases the integrity of sperm plasma membrane, which might be an important factor of male infertility.


Neurocirculatory analysis of potential EIAB patients.
Twelve patients with gross vascular occlusions and with infarcts demonstrated in CT were examined with regard to their hemodynamic situation. Angiography and rCBF with intra-arterial and inhalation techniques were performed. Response to increased arterial hypertension and to CO2 inhalation was tested. It is concluded that one technique alone does not provide enough information for the selection of patients suitable for EIAB operation.


Identification of a VxP Targeting Signal in the Flagellar Na+ /K+ -ATPase.
Na(+) /K(+) -ATPase (NKA) participates in setting electrochemical gradients, cardiotonic steroid signaling and cellular adhesion. Distinct isoforms of NKA are found in different tissues and subcellular localization patterns. For example, NKA α1 is widely expressed, NKA α3 is enriched in neurons and NKA α4 is a testes-specific isoform found in sperm flagella. In some tissues, ankyrin, a key component of the membrane cytoskeleton, can regulate the trafficking of NKA. In the retina, NKA and ankyrin-B are expressed in multiple cell types and immunostaining for each is striking in the synaptic layers. Labeling for NKA is also prominent along the inner segment plasma membrane (ISPM) of photoreceptors. NKA co-immunoprecipitates with ankyrin-B, but on a subcellular level colocalization of these two proteins varies dependent on the cell type. We used transgenic Xenopus laevis tadpoles to evaluate the subcellular trafficking of NKA in photoreceptors. GFP-NKA α3 and α1 are localized to the ISPM, but α4 is localized to outer segments (OSs). We identified a VxP motif responsible for the OS targeting by using a series of chimeric and mutant NKA constructs. This motif is similar to previously identified ciliary targeting motifs. Given the structural similarities between OSs and flagella, our findings shed light on the subcellular targeting of this testes-specific NKA isoform.


The Treatment of Heterotopic Human Colon Xenograft Tumors in Mice with 5-Fluorouracil Attached to Magnetic Nanoparticles in Combination with Magnetic Hyperthermia Is More Efficient than Either Therapy Alone.
Magnetic nanoparticles (MNPs) have shown promising features to be utilized in combinatorial magnetic hyperthermia and chemotherapy. Here, we assessed if a thermo-chemotherapeutic approach consisting of the intratumoral application of functionalized chitosan-coated MNPs (CS-MNPs) with 5-fluorouracil (5FU) and magnetic hyperthermia prospectively improves the treatment of colorectal cancer. With utilization of a human colorectal cancer (HT29) heterotopic tumor model in mice, we showed that the thermo-chemotherapeutic treatment is more efficient in inactivating colon cancer than either tumor treatments alone (i.e., magnetic hyperthermia vs. the presence of 5FU attached to MNPs). In particular, the thermo-chemotherapeutic treatment significantly (p < 0.01) impacts tumor volume and tumor cell proliferation (Ki67 expression, p < 0.001) compared to the single therapy modalities. The thermo-chemotherapeutic treatment: (a) affects DNA replication and repair as measured by H2AX and phosphorylated H2AX expression (p < 0.05 to 0.001), (b) it does not distinctly induce apoptosis nor necroptosis in target cells, since expression of p53, PARP cleaved-PARP, caspases and phosphorylated-RIP3 was non-conspicuous, (c) it renders tumor cells surviving therapy more sensitive to further therapy sessions as indicated by an increased expression of p53, reduced expression of NF-κB and HSPs, albeit by tendency with p > 0.05), and (d) that it impacts tumor vascularity (reduced expression of CD31 and αvβ3 integrin (p < 0.01 to 0.001) and consequently nutrient supply to tumors. We further hypothesize that tumor cells die, at least in parts, via a ROS dependent mechanism called oxeiptosis. Taken together, a very effective elimination of colon cancers seems to be feasible by utilization of repeated thermo-chemotherapeutic therapy sessions in the long-term.


Age-related changes in female femoral neck geometry: implications for bone strength.
Bone strength is a function of both bone mass and its geometric distribution, a factor that is obscured in the conventional bone mineral analysis. Structural geometry is particularly important in areas such as the femoral neck that are exposed to bending loads in vivo. Here we present results of a study examining age changes in the structural geometry of the female femoral neck derived from dual photon absorptiometry (DPA) data. In a previous study, differences in the aging patterns of males and females over the entire adult age range were demonstrated. In that study, only males showed "compensatory" geometric restructuring of the femoral neck which tended to offset loss of bone mineral with age. In the present study, femoral neck structural properties from 1044 women were examined for aging trends before and after the approximate age of menopause (50 years). Women in the premenopausal age range showed a 4% decline per decade in femoral neck BMD, but no change in the femoral neck cross-sectional moment of inertia (CSMI). This aging pattern is similar to that of males in our earlier study, and in both cases resulted in little or no increase in femoral neck bending stresses. After age 50, however, women show a more rapid decline in femoral neck BMD (7% per decade) accompanied by a decline in CSMI of 5% per decade. These changes result in increases in femoral neck stresses of 4-12% per decade due to the apparent lack of compensatory restructuring to offset the loss of bone mineral.(ABSTRACT TRUNCATED AT 250 WORDS)


Dynamics of depolarization and hyperpolarization in the frontal cortex and saccade goal.
The frontal eye field and neighboring area 8Ar of the primate cortex are involved in programming and execution of saccades. Electrical microstimulation in these regions elicits short-latency contralateral saccades. To determine how spatiotemporal dynamics of microstimulation-evoked activity are converted into saccade plans, we used a combination of real-time optical imaging and microstimulation in behaving monkeys. Short stimulation trains evoked a rapid and widespread wave of depolarization followed by unexpected large and prolonged hyperpolarization. During this hyperpolarization saccades are almost exclusively ipsilateral, suggesting an important role for hyperpolarization in determining saccade goal.


A whole-genome admixture scan finds a candidate locus for multiple sclerosis susceptibility.
Multiple sclerosis is a common disease with proven heritability, but, despite large-scale attempts, no underlying risk genes have been identified. Traditional linkage scans have so far identified only one risk haplotype for multiple sclerosis (at HLA on chromosome 6), which explains only a fraction of the increased risk to siblings. Association scans such as admixture mapping have much more power, in principle, to find the weak factors that must explain most of the disease risk. We describe here the first high-powered admixture scan, focusing on 605 African American cases and 1,043 African American controls, and report a locus on chromosome 1 that is significantly associated with multiple sclerosis.


Isolation and characterization of the SUD1 gene, which encodes a global repressor of core promoter activity in Saccharomyces cerevisiae.
The SUD1 gene was identified during a hunt for mutants that are able to express an sta1 gene (encoding an extracellular glucoamylase) lacking an upstream activation sequence (UAS) for transcription. A null allele of sud1 alleviated the transcriptional defect of the UAS-less sta1 and also suppressed mutations in trans-acting genes (GAM1/SNF2 and GAM3/ADR6) required for transcription of STA1. The mutation also increased expression from various core promoters (CYC1, CUP1, HIS3, PUT1, and PUT2), suggesting that the SUD1 protein is a global transcriptional regulator that plays a negative role at or near the TATA element. However, the SUD1 function was ineffective on promoters containing a UAS from either STA1 or GAL10 under derepressed conditions. The sud1 mutation suppressed the salt-sensitive cell growth phenotype caused by elevated levels of the TATA-binding protein (SPT15), further suggesting a transcriptional role for SUD1. sud1 cells showed additional pleiotropic phenotypes: temperature-sensitive (ts) growth, reduced efficiencies of sporulation, and sensitivity to heat shock and nitrogen starvation. The SUD1 gene is predicted to encode a 64 kDa, hydrophilic protein.


Analysis of heterogeneity in daunorubicin uptake by human leukemia cells using laser flow cytometry.
Heterogeneity in daunorubicin uptake by leukemic blast cells obtained from the bone marrow of 16 patients with acute leukemia (10 acute nonlymphocytic leukemia and 6 acute lymphocytic leukemia) was determined by laser flow cytometry following drug treatment in vitro for 1 hr. Fluorescence profiles of cellular anthracycline levels in the various samples indicated a marked heterogeneity in daunorubicin uptake and the range of detectable drug fluorescent cells was 34%-99%. A retrospective analysis of disease outcome in these patients who were treated with a daunorubicin or doxorubicin containing induction regimen indicated the following: (a) 8 of 11 patients who entered complete remission had greater than 80% of leukemic blast cells accumulating detectable amounts of daunorubicin; and (b) 3 of 4 patients who did not respond to chemotherapy had less than 40% of the leukemic blast cells accumulating detectable amounts of daunorubicin. These results suggest that laser flow cytometry may be useful in determining qualitative and quantitative differences in daunorubicin levels in heterogeneous tumor cell populations.


Heritability and intrafamilial aggregation of arterial characteristics.
We investigated the heritability and familial aggregation of various indexes of arterial stiffness and wave reflection and we partitioned the phenotypic correlation between these traits into shared genetic and environmental components. Using a family-based population sample, we recruited 204 parents (mean age, 51.7 years) and 290 offspring (29.4 years) from the population in Cracow, Poland (62 families), Hechtel-Eksel, Belgium (36), and Pilsen, the Czech Republic (50). We measured peripheral pulse pressure (PPp) sphygmomanometrically at the brachial artery; central pulse pressure (PPc), the peripheral augmentation indexes (PAIxs) and central augmentation indexes (CAIxs) by applanation tonometry at the radial artery; and aortic pulse wave velocity (PWV) by tonometry or ultrasound. In multivariate-adjusted analyses, we used the ASSOC and PROC GENMOD procedures as implemented in SAGE and SAS, respectively. We found significant heritability for PAIx, CAIx, PPc and mean arterial pressure ranging from 0.37 to 0.41; P < or = 0.0001. The method of intrafamilial concordance confirmed these results; intrafamilial correlation coefficients were significant for all arterial indexes (r > or = 0.12; P < or = 0.02) with the exception of PPc (r = -0.007; P = 0.90) in parent-offspring pairs. The sib-sib correlations were also significant for CAIx (r = 0.22; P = 0.001). The genetic correlation between PWV and the other arterial indexes were significant (rhoG > or = 0.29; P < 0.0001). The corresponding environmental correlations were only significantly positive for PPp (rhoE = 0.10, P = 0.03). The observation of significant intrafamilial concordance and heritability of various indexes of arterial stiffness as well as the genetic correlations among arterial phenotypes strongly support the search for shared genetic determinants underlying these traits.


Selective damage to tree-seedlings by bank voles (Clethrionomys glareolus).
(1) Small saplings of Tilia cordata, when planted in deciduous woodlands, are damaged or destroyed by rodents. (2) Experiments with captive animals show that the damage is identical with that caused by bank voles. (3) Bank voles are present at all sites where damage occurs. (4) Small saplings of Betula spp. established naturally in the sites are very rarely damaged. (5) Seedlings of Quercus spp. and Fagus silvatica are damaged or destroyed but small saplings suffer little or no damage attributable to voles. (6) Experiments with captive bank voles demonstrate marked differences between species of tree in their susceptibility to damage. (7) Tilia cordata is often severely damaged or destroyed. (8) Betula spp. suffer little or no damage. (9) Damage and destruction of small saplings is an important factor in the failure of regeneration of T. cordata in English woodlands because of the low density of seedlings and low frequency of large crops of fertile fruits.


Effects of Standardized Exercise Tests on Plasma Thyroid Hormones' Kinetics in Standardbred Racehorses.
This study examined how a standard exercise test (SET) affected (1) thyroid hormones (THs) of horses and (2) the relationship between the VLa4 of horses and TH responses to the exercise in trained Standardbred racehorses (VLa4 is the velocity run at defined conditions at which a blood lactate concentration of 4 mmol/L is determined). Twelve trained Standardbred racehorses (six stallions and six mares) performed SETs until the horses' blood lactate concentration was at or above 4 mmol/L. The horses were divided into three age groups (2, 3, and 4 years old); each group consists of 4 horses respectively (two male and two female), to evaluate the effects of age and sex on hormonal responses to SET. During each SET, blood samples were taken at rest and after each interval and at the end of SET. Blood was analysed for total and free triiodothyronine (T3, fT3) as well as total and free thyroxine (T4, fT4). The statistical model included three fixed factors (SET, sex and age) and their main interactions. ANOVA analysis revealed that T3 and fT3 were significantly influenced by SETs. Plasma T3 and fT3 concentrations were higher in 4-year-old horses compared to the other age groups. All plasma THs concentrations were higher in mares than in stallions. Correlations revealed that a higher VLa4 was negatively related to all THs responses in 2-year-old Standardbred mares only. The SET used to determine VLa4 increased selected THs (T3, fT3); these increases were inversely related to VLa4 and affected by age and sex of the horses. The correlation of VLa4 with thyroid exercise' response might provide some additional information for performance evaluation of Standardbred racehorses, especially for evaluating training adaptation, according to sex, and age. Further studies are necessary to provide support on the value of measuring THs in Standardbred racehorses of different sex and age.


Testicular expression of SP-A, SP-D and MBL-A is positively regulated by testosterone and modulated by lipopolysaccharide.
Pattern recognition proteins viz., Surfactant Protein-A (SP-A), Surfactant Protein-D (SP-D) and Mannan Binding Lectin-A (MBL-A) regulate inflammatory immune responses. In view of their plausible contribution to immune privilege in testis, the present study explored their expression and regulation in murine testis. The testicular expression of SP-A, SP-D and MBL-A significantly increased at puberty and was significantly down-regulated in testosterone suppression model. Of the isolated germ cells, Sertoli cells, myoid cells and Leydig cells, germ cells expressed SP-A, SP-D and MBL-A while myoid cells were found to express MBL-A. SP-A and SP-D were localised on head and tail of murine caudal sperm, whereas MBL-A was observed on the connecting piece and tail. Systemic lipopolysaccharide challenge significantly up-regulated SP-A and SP-D levels in murine testis after 24h. Positive regulation of collectins by testosterone and their modulation in response to inflammation implicates their involvement in testicular immune-privilege.


Assessment of maternal knowledge of infant movement and nutrition guidelines in Canada: The PREVENT survey study (Physical activity, Rest, Exercise and nutrition Values for Education of New moms with Type 2 diabetes/gestational diabetes).
Infants born to mothers with type 2 diabetes (T2D) and gestational diabetes (GDM) are at an increased risk of being overweight/obese. Modifiable lifestyle factors play a role in prevention of overweight and obesity. In 2017, the Canadian 24 h Movement Guidelines for the Early Years (CMG) were released. Alongside physical activity recommendations, sweetened beverage consumption (SBC) recommendations were also released by the American Academy of Pediatrics in 2017. The objective of this study was to determine the knowledge pregnant women with T2D and GDM have on the CMG and SBC recommendations, and to determine what factors affect this. A survey with questions regarding demographics, socioeconomic variables and the CMG and SBC recommendations was administered to pregnant women at Diabetes in Pregnancy clinics in Calgary, Alberta from July 2019 to January 2020. Surveys were analyzed utilizing the non-parametric Kruskall-Wallis Rank-Sum test, chi-square test and linear regression. A total of 79 respondents with T2D and GDM were collected. Respondents had the highest knowledge of SBC recommendations and the lowest knowledge of CMG recommendations. A bachelor's or higher degree was associated with significantly higher knowledge scores than a high-school education or less. In conclusion, pregnant women with T2D and GDM in this study had overall poor knowledge of the CMG and SBC recommendations, with less knowledge regarding the CMG. Level of education was found to be associated with knowledge regarding these recommendations. Future programs to improve education around infant and toddler physical activity and SBC recommendations may be beneficial for this patient population.


AMPA receptor activation potentiates zinc neurotoxicity.
Extracellular Zn2+ attenuates NMDA receptor-mediated neurotoxicity and increases AMPA receptor-mediated toxicity. Known electrophysiological effects of Zn2+ predict only the former. We considered the possibility that the latter rather reflects AMPA potentiation of Zn2+ toxicity, perhaps mediated by neuronal depolarization and Zn2+ entry through voltage-gated Ca2+ channels. High K+ or kainate also potentiated Zn2+ toxicity, and AMPA plus Zn2+ toxicity was attenuated by raising extracellular Ca2+, or by Ca2+ channel blockers. AMPA plus Zn2+ exposure induced an increase in fluorescence from neurons loaded with the Zn(2+)-sensitive dye TS-Q and increased subsequent 45Ca2+ accumulation. The ability of AMPA receptor activation to potentiate Zn2+ toxicity may be relevant to neuronal death associated with intense activation of glutamatergic pathways.


Smart nanotheranostic hydrogels for on-demand cancer management.
Theranostics is a revolution in cancer therapy. Hydrogels have many implications as a drug delivery vehicle and theranostics hydrogels could be a model nanotherapeutic for simultaneous cancer diagnosis and treatment.


Epithelium-on corneal collagen crosslinking for management of advanced keratoconus.
To report the 1-year visual and keratometric results of epithelium-on corneal collagen crosslinking (CXL) for advanced keratoconus (median maximum keratometry [K] ≥58.0 diopters [D]). School of Ophthalmology and Optometry and Eye Hospital of Wenzhou Medical College, Wenzhou, China. Prospective case series. Patients with bilateral progressive keratoconus had tetracaine-enhanced epithelium-on CXL. The worse eye had CXL, and the fellow eye was not treated. Results were reported 1, 3, 6, and 12 months postoperatively. The outcomes were compared with those in the fellow untreated eyes. Twenty-one eyes of 21 patients with a median age of 20.4 years (interquartile range [IQR], 9.5 years) were treated. A significant improvement in postoperative uncorrected distance visual acuity was observed at 12 months (P = .002). Postoperative corrected distance visual acuity improved at 6 months and 12 months (P ≤ .009) compared with baseline values. The maximum K decreased by 1.63 D from the median preoperative maximum K of 62.7 D (IQR, 12.9 D) at 12 months (P < .001). The reduction in maximum K was higher after CXL than in untreated eyes at the end of 12 months (P = .001). Correlation analysis between the preoperative maximum K values and the change over 6 to 12 months between different studies showed a significant correlation (r = -0.764, P < .001; Spearman correlation). Epithelium-on CXL was an effective treatment for patients with advanced keratoconus. A higher preoperative maximum K value correlated with greater corneal flattening after CXL. None of the authors has a financial or proprietary interest in any material or method mentioned.


Life events, meaning and narrative: the case of infidelity and divorce.
This article examines how three interviewees construct the meaning of the 'same' life events--marital infidelity and divorce--in radically different ways. All three narrate their experience, using narrative structures to reconstruct and interpret events and yet, because they have different points to make about the spouses' affairs and their divorces, they combine story elements in contrasting ways. Using narrative analysis, I show that what on the surface appear to be the same life events are, in fact, quite different events. I argue that stress research needs to attend more closely to the personal meanings of life events, and show how narrative methods can enrich studies of stress by illuminating how individuals make sense of difficult experiences.


[Organizational redistribution of Ukrainian war wounded for care in Germany].
Due to the war in Ukraine, which began on February 24th, 2022, countless people are injured every day, regardless of whether they are civilians or soldiers. This has led to the Ukrainian healthcare system being massively overburdened and for this reason these patients are brought to Germany, among other places, to be treated here. This article is intended to show the way and the organizational effort required to distribute the patients to the clinics in Germany.


Girdling effect of adynamic cardiomyoplasty in a model of dilated cardiomyopathy.
The potential benefits of adynamic cardiomyoplasty remain unclear. We determined whether unstimulated skeletal muscle wrap alone prevents or attenuates progressive left ventricular dilation in a canine model of congestive heart failure produced by repeated intracoronary infusions of doxorubicin. 14 dogs were randomized in to 2 groups, 1 undergoing cardiomyoplasty (CMP group) and 1 that did not (CONT group). Intracoronary doxorubicin was administered weekly for 5 weeks to induce heart failure. Hemodynamic data was obtained before infusion and 5 weeks afterward. Echocardiography was done weekly. Significant left ventricular dilation was observed in the CONT group--left ventricular end-diastolic diameter increased from 28.9 +/- 2.7 to 38.5 +/- 3.3 mm (p < 0.05). Significant left ventricular dilation was also observed in the CMP group--left ventricular end-diastolic diameter increased from 28.9 +/- 3.3 to 38.0 +/- 4.2 mm (p < 0.05). Dilation was slower in the CMP group than in the CONT group, however. Ejection fraction decreased from 58.0 +/- 13.8 to 29.9 +/- 13.7% in the CONT group, but was preserved from 56.0 +/- 8.8 to 51.9 +/- 10.3% in the CMP group. Adynamic cardiomyoplasty reduces ventricular dilation associated with heart failure without exacerbating left ventricular dysfunction.


18F-FDG PET/CT in asymptomatic patients with COVID-19: the submerged iceberg surfaces.
The aim of this case series is to describe our experience in diagnosis and management of oncological asymptomatic patients with COVID-19 who underwent 18F-FDG PET/CT. From March 9 to March 31, 2020, we identified 5 patients who had PET/CT findings suspicious for COVID-19, but no symptom of infection. The first three patients were administered an SARS-CoV-2 test in a COVID-dedicated center, while the fourth and fifth were tested in our institution, in accordance with a new internal procedure. The SARS-CoV-2 test yielded positive results in all five patients. In this COVID-19 emergency, our task as radiologists and nuclear medicine physicians is to be able to identify imaging findings suggestive of the disease and to manage patients without overloading the hospital system.


Liver membrane autoantibodies in chronic active hepatitis. Studies on mechanically and enzymatically isolated rabbit hepatocytes.
Target antigens relevant for immune reactions in inflammatory liver diseases should be expressed on the hepatocellular membrane. Using mechanically or enzymatically isolated rabbit hepatocytes, we evaluated the influence of cell integrity on the detection of membrane-expressed antigens by sera from patients with chronic hepatitis and by murine monoclonal antibodies. Our results provide evidence that target antigens of liver membrane autoantibodies (LMA) as well as liver kidney microsomal antibodies (LKM) are not expressed on the hepatocellular membrane of viable and intact isolated rabbit hepatocytes. However, LMA were detected in the sera of 56% of patients with autoimmune chronic active hepatitis using mechanically isolated hepatocytes. These findings underline the diagnostic relevance of the autoantibodies. It is suggested that LMA are directed against constituents of the cytoskeleton. Therefore, it seems to be unlikely that this antibody is causally involved in the pathogenesis of autoimmune liver diseases.


Fate mapping of Trps1 daughter cells during cardiac development using novel Trps1-Cre mice.
Tricho-rhino-phalangeal syndrome (TRPS) is a rare congenital disorder that is characterized by abnormal hair growth and skeletal deformities. These result in sparse hair, short stature, and early onset of joint problems. Recent reports have shown that a relatively high proportion of patients with TRPS exhibit a broad range of congenital heart defects. To determine the regulation of Trps1 transcription in vivo, we generated novel transgenic mice, which expressed Cre recombinase under the murine Trps1 proximal promoter sequence (Trps1-Cre). We crossed these mice with Cre reporter mice to identify Trps1 daughter cells. Labeled cells were observed in the appendicular joint tissue, dermal papilla of the hair follicles, cardiac valves, aortic sinus, atrial walls, and the interventricular septum. In situ analysis showed restricted Trps1 expression, which was observed in endocardial cushions of the outflow tract, and in leaflets of all mature cardiac valves. These results suggest that the Trps1 proximal promoter sequence contains some of the tissue-specific Trps1 regulatory region. Further, our findings partially explain why patients with TRPS show a broad range of congenital cardiac defects, although Trps1 expression is observed in a more restricted fashion. genesis 54:379-388, 2016. © 2016 Wiley Periodicals, Inc.


Simulated gastrointestinal digestion of polylactic acid (PLA) biodegradable microplastics and their interaction with the gut microbiota.
The accumulation of microplastics (MPs) in the environment as well as their presence in foods and humans highlight the urgent need for studies on the effects of these particles on humans. Polylactic acid (PLA) is the most widely used bioplastic in the food industry and medical field. Despite its biodegradability, biocompatibility, and "Generally Recognized As Safe" (GRAS) status, recent animal model studies have shown that PLA MPs can alter the intestinal microbiota; however, to date, no studies have been reported on the possible gut and health consequences of its intake by humans. This work simulates the ingestion of a realistic daily amount of PLA MPs and their pass through the gastrointestinal tract by combining the INFOGEST method and the gastrointestinal simgi® model to evaluate possible effects on the human colonic microbiota composition (16S rRNA gene sequencing analysis) and metabolic functionality (lactic acid and short-chain fatty acids (SCFA) production). Although PLA MPs did not clearly alter the microbial community homeostasis, increased Bifidobacterium levels tended to increase in presence of millimetric PLA particles. Furthermore, shifts detected at the functional level suggest an alteration of microbial metabolism, and a possible biotransformation of PLA by the human microbial colonic community. Raman spectroscopy and field emission scanning electron microscopy (FESEM) characterization revealed morphological changes on the PLA MPs after the gastric phase of the digestion, and the adhesion of organic matter as well as a microbial biofilm, with surface biodegradation, after the intestinal and colonic phases. With this evidence and the emerging use of bioplastics, understanding their impact on humans and potential biodegradation through gastrointestinal digestion and the human microbiota merits critical investigation.


A cytotoxic monoclonal IgM antibody (Tü 101) directed against an antigenic determinant shared between the HLA-A allospecificities A2 and A28.
A complement-fixing murine monoclonal IgM antibody (TU 101) strictly directed against a supertypic determinant present on the HLA-A locus antigens A2 and A28 was defined from a fusion experiment employing T cell blasts as immunizing cells. The specificity of this antibody was established in the microcytotoxicity assay on 91 normal Caucasian blood donors, as well as in the SpA-Ig assay on a panel of lympho- and hematopoietic cell lines. TU 101 segregates only with its defined HLA allotypes in families. This reagent may be of particular value as a probe for analyzing a molecular relationship of different antigenic determinants on the HLA-A2 and A28 specificities in comparison with two recently defined anti-HLA-A2/A28 monoclonal antibodies and may help to characterize structural variations of these HLA-molecules on a serological and immunochemical basis.


Post-operative Venous Thromboembolism in Patients Operated on for Aorto-iliac Obstruction and Abdominal Aortic Aneurysm, and the Application of Pharmacological Thromboprophylaxis.
In light of the methods generally used to assess the risk of venous thromboembolism (VTE), major vascular operations should be regarded as high risk procedures. Nevertheless, no principles for implementing and maintaining thromboprophylaxis have so far been developed. The aim of this study was to determine the frequency and nature of VTE occurrence in patients routinely applying pharmacological thromboprophylaxis following implantation of an aorto-bifemoral prosthesis. The prospective non-randomized study included 105 patients with aortoiliac obstruction and 119 patients with abdominal aortic aneurysm (AAA) treated surgically. During hospitalization pharmacological thromboprophylactic procedures were observed. A duplex test was performed on the day before surgery, on the day of discharge, and 30 days after the patients had left the hospital. VTE was detected in 18.1% of the patients with aortoiliac obstruction (9.5% of patients during hospitalization and 8.6% of patients after discharge). VTE was diagnosed in 21.0% of patients with AAA (15.1% of patients during hospitalization and 5.9% of patients after discharge). The incidence of VTE was comparable in both groups, both during hospitalization (p = .51) and in the 30 day period following the end of hospitalization (p = .48). It is advisable that before hospital discharge routine duplex ultrasonography tests should be conducted on the venous systems of all patients who have undergone major vascular operations. It is likewise advisable to consider whether thromboprophylaxis for vascular patients should be extended beyond their discharge from hospital.


The B-cell repertoire in myasthenia gravis includes all four acetylcholine receptor subunits.
By enumerating cells secreting IgG antibodies of particular specificities using an enzyme-linked immunospot (ELISPOT) assay, the B-cell responses to Torpedo acetylcholine receptor (AChR) and its alpha-, beta-, gamma- and delta-subunits in peripheral blood from patients with myasthenia gravis (MG), and controls with other neurological diseases (OND) as well as healthy subjects were determined. Compared to controls, the patients with MG had elevated numbers of B cells secreting antibodies against AChR and its alpha-, beta-, gamma- and delta-subunits in peripheral blood in parallel. The mean numbers of anti-AChR antibody secreting cells were about 17 per 10(5) blood MNC, and for the subunits 10 to 15 in MG patients, compared to between 0.8 and 1.9 per 10(5) blood MNC in OND patients, and 0.1 to 0.3 in healthy controls. Such B cells detected in controls probably represent naturally occurring B cells responded to AChR and its subunits. The finding that most (60%) MG patients had B cells predominantly recognizing the alpha-subunit may be an indirect argument for the existence of a main immunogenic region (MIR). In the remaining 40% of patients with MG the predominant B-cell responses were directed to beta-, gamma- or delta-subunit. The data suggest that all four AChR subunits may function as strong immunogens in MG, though the alpha-subunit may be the major immune target in a substantial proportion of MG patients.


Tumor Endothelial Cells-Associated Integrin Alpha-6 as a Promising Biomarker for Early Detection and Prognosis of Hepatocellular Carcinoma.
HCC remains a lethal cancer type, with early detection being critical for improved patient outcomes. This study introduces a comprehensive methodological approach to identify the ITGA6 gene as a potential blood marker for early HCC (eHCC) detection. We initially analyzed the GSE114564 dataset encompassing various stages of liver disease, identifying 972 differentially expressed genes in HCC. A refined analysis yielded 59 genes specifically differentially expressed in early HCC, including ITGA6. Subsequent validation in multiple datasets confirmed the consistent upregulation of ITGA6 in HCC. In addition, when analyzing progression-free survival (PFS) within the entire patient cohort and overall survival (OS) specifically among patients classified as tumor grade G1, the group of patients characterized by high expression levels of ITGA6 displayed an elevated risk ratio in relation to prognosis. Further analyses demonstrated the predominant expression of ITGA6 in TECs and its enrichment in angiogenesis-related pathways. Additionally, positive correlations were found between ITGA6 expression and pro-tumorigenic immune cells, but not with anti-tumorigenic immune cells. Our study elucidates the potential of ITGA6 as a blood-based marker for HCC early detection and diagnosis and its complex interplay with the tumor microenvironment. Further research may lead to novel strategies for HCC management and patient care.


Characterization of kidney stones using thermogravimetric analysis with electron dispersive spectroscopy.
Urinary calculi are formed from a result of biological mal-adjustment of urine leading to deposits of salt and mineral crystals along the urinary collecting system. They are usually multiphasic material with complex compositions. The objective of this study is to identify and characterize a series of urinary calculi samples using a combination of thermogravimetric analysis (TGA) with electron dispersive spectroscopy (EDS). These samples were retrieved during percutaneous nephrolithotripsy. Additional characterization by hardness value and microstructure is also carried out for co-relation study. The samples are found to be uric acid, calcium oxalates and magnesium ammonium phosphate hexahydrate. TGA is indeed one of the viable analytical tools for urinary calculi as it is fast and simple. The combinational application of EDS is beneficial when there is a need for differentiated qualitative chemical composition detection at the identified nuclei position for urinary calculi with spatial variation in composition. The combination of TGA and EDS will thus facilitate the correct diagnosis and treatment by clinicians.


[Development of a protocol on pulsed field gel electrophoresis analysis for Streptococcus suis].
To develop a PFGE protocol for Streptococcus suis. We developed and optimized a PFGE protocol for S. suis, in terms of plug preparation, choice of restriction endonucleases and optimized electrophoresis parameters. By analyzing the genome sequences of S. suis P1/7 with Mapdraw of DNAStar, we found three restriction enzymes, Swa I, Sma I and Apa I, were more suitable than others. Analysis of 100 isolates of S. suis including 34 of 35 serotypes identified, 59, 53 and 43 patterns were obtained from Swa I, Sma I and Apa I restriction, respectively. The enzyme Swa I had the greatest power for discrimination ability. By optimization of the protocol at various conditions, a rapid, reproducible, economic and practical PFGE method for S. suis was developed.


[Atresia of the tricuspid valve and total anomalous supracardiac pulmonary venous return. Description of a case associated with severe extracardiac malformations].
The Authors report a case of tricuspid atresia and total anomalous pulmonary venous return of the supracardiac type, with mild pulmonary valve stenosis and extracardiac malformations as anal atresia, microphthalmia and irideo and chorioretinic coloboma. The Authors stress the importance of the electrocardiogram and standard chest X-Ray to "suspect" this rare association.


Inhibition of enzymatic browning and protection of sulfhydryl enzymes by thiol compounds.
In a reaction between (-)-epicatechin (EC) and 2-mercaptoethanol (2ME), catalyzed by partially purified polyphenol oxidase (PPO) extracted from the style of Rhododendron mucronatum, 2'-(2-hydroxyethylthio)-(-)-epicatechin (2'-HETEC), 5'-(2-hydroxyethylthio)-(-)-epicatechin (5'-HETEC), and 2',5'-bis(2-hydroxyethylthio)-(-)-epicatechin (2',5'-HETEC) were formed. The rate of formation of 2',5'-HETEC from 5'-HETEC was faster than that from 2'-HETEC. In the absence of 2ME, the concentration of EC decreased rapidly and the reaction mixture turned brown; 2'-, 5'-, and 2',5'-HETEC, especially 2'-substituted HETECs. reacted more slowly. These data indicate that 2ME acts both as an inhibitor of the polymerization of O-quinone, presumably by binding to it and as a reductant involved in the conversion of O-quinone to O-dihydroxyphenol, Inhibition of enzymatic browning by other thiol compounds such as cysteine and dithiothreitol was also investigated.


Between scylla and charybdis: a bleomycin-exposed patient with Cohen syndrome.
Chemotherapy with bleomycin may cause a syndrome of pulmonary sensitivity to supranormal inspired oxygen concentrations that persists for an unknown period of time after exposure. We present a mentally retarded adolescent patient in whom supranormal inspired oxygen was temporarily necessary to manage her difficult airway. Subsequently her pulmonary function deteriorated acutely and, after intermittent stabilization, irreversibly. In this case, bleomycin exposure may have played a pivotal role in modulating minor insults to trigger fatal acute respiratory distress syndrome (ARDS).


Dipeptidyl Peptidase-4 Is a Pro-Recovery Mediator During Acute Hepatotoxic Damage and Mirrors Severe Shifts in Kupffer Cells.
Dipeptidyl peptidase-4 (DPP-4 or clusters of differentiation [CD]26) is a multifunctional molecule with established roles in metabolism. Pharmacologic inhibition of DPP-4 is widely used to improve glycemic control through regulation of the incretin effect. Colaterally, CD26/DPP-4 inhibition appears to be beneficial in many inflammatory conditions, namely in delaying progression of liver pathology. Nevertheless, the exact implications of CD26/DPP-4 enzymatic activity in liver dysfunction remain unclear. In this work, we investigated the involvement of CD26/DPP-4 in experimental mouse models of induced hepatocyte damage that severely impact Kupffer cell (KC) populations. Liver dysfunction was evaluated in CD26 knockout (KO) and B6 wild-type mice during acute liver damage induced by acetaminophen, chronic liver damage induced by carbon tetrachloride, and KC-depleting treatment with clodronate-loaded liposomes. We found that necrosis resolution after hepatotoxic injury was delayed in CD26KO mice and in B6 mice treated with the CD26/DPP-4 inhibitor sitagliptin, suggesting that DPP-4 enzymatic activity plays a role in recovering from acute liver damage. Interestingly, the severe KC population reduction in acute and chronic liver injury was concomitant with increased CD26/DPP-4 serum levels. Remarkably, both chronic liver damage and noninflammatory depletion of KCs by clodronate liposomes were marked by oscillation in CD26/DPP-4 serum activity that mirrored the kinetics of liver KC depletion/recovery. Conclusion:CD26/DPP-4 enzymatic activity contributes to necrosis resolution during recovery from acute liver injury. Serum CD26/DPP-4 is elevated when severe perturbations are imposed on KC populations, regardless of patent liver damage. We propose that serum CD26/DPP-4 is a potential systemic surrogate marker of severe impairments in the KC population imposed by clinical and subclinical liver conditions.


Late Identification of a Stealthy Aorto-Pulmonary Window: A Case Report.
The term "aortopulmonary window" (APW), often referred to as "aortopulmonary septal defect," refers to a rare congenital medical disorder where there is an improper direct link between the main pulmonary artery and the ascending aorta. It can be combined with other cardiac congenital conditions or be an isolated lesion. Herein, we report the incidental discovery of a minor, restrictive aortopulmonary septal defect in a 60-year-old male who denied having any clinical symptoms. Incidentally detected APW in adulthood is uncommon and, hence, can be readily overlooked, a fortiori, in asymptomatic patients.


Narrative means to humanistic ends.
Efforts to "rehumanize" medical education through curriculum reform and program development have been numerous and ongoing in recent years. One particularly intriguing contribution has come from the area of narrative studies. It is now common to use literature in general, and physician--patient narratives in particular, both to expand students' understanding of the clinical encounter and to sensitize them to the humanistic aspects of medicine. In this article, we describe the process by which we have introduced key insights from and elements of narrative theory into our 1st-year clinical skills program. Rather than limiting our efforts to the use of literature and to the description of individual narrative encounters, however, we have framed our entire course as an exercise in narrative construction. We refer to this process as "narrative structuring." A combination of short essays on topics related to the various literary materials utilized in the course, written reports on ethical aspects of the clinical cases presented in the clinical skills sessions, and student journaling are integral components of the evaluation of this course. Characterizing our course in terms of narrative structuring serves both to integrate the various elements of our complex curriculum around a common theme and to remind both students and faculty alike of the privileges and responsibilities we share as we participate in the writing of one another's stories.


Bilateral breast reconstruction with deep inferior epigastric perforator flaps in slim patients.
Slim women are not always considered candidates for bilateral autologous breast reconstruction. The study aims to assess the volume considerations and complications of deep inferior epigastric perforator (DIEP) flap in bilateral breast reconstruction among slim patients. All patients undergoing bilateral DIEP breast reconstruction at the Royal Marsden Hospital, London, September 2007-March 2015, were reviewed. Flap weight was compared to mastectomy weight (weight ratio) and complications were recorded. Subgroup analyses according to Body Mass Index (BMI) were performed. One-hundred seventy patients (340 flaps) were included. There were 42 in the slim-group (BMI <25) (84 flaps), 70 in the traditional (BMI = 25.0-29.9) (140 flaps), and 58 in the obese (BMI >30) (116 flaps). There were no significant differences in reconstruction weight ratio between the slim and the traditional groups (1.04 ± 0.31 versus 0.95 ± 0.38, p = .267). When comparing the slim to obese group the ratio was lower for the obese group, inferring that a larger reconstruction was performed (p = .016). Complications was less frequent in the slim group compared to the traditional and the obese groups (31% compared to 50% and to 53% (p = .060 and p = .021, respectively). Donor-site specific complications did not differ between groups (29% 26% and 29%; p = .823 and .830, respectively). The DIEP flaps may be a safe option for bilateral breast reconstruction among patients with BMI <25 without sacrifice in volume or increase in donor-site complications; low BMI does not in itself contraindicate bilateral DIEP breast reconstruction.


Utility of the social vulnerability index to risk stratify atrial fibrillation mortality outcomes.
Multiple methods of quantifying social determinants of health exist, such as the social vulnerability index (SVI). We assess the impact of the SVI on atrial fibrillation (AF)-related cardiovascular disease mortality. CDC databases were used to obtain mortality and SVI information. Age-adjusted mortality rates (AAMR) were compared among all US counties, aggregated by SVI quartiles. AAMR was not increased in counties within the highest SVI quartile, consistent across gender and geographic subgroups. Increased SVI is a poor marker to predict mortality outcomes associated with AF.


Dark Matter RNA: Existence, Function, and Controversy.
The mysteries surrounding the ∼97-98% of the human genome that does not encode proteins have long captivated imagination of scientists. Does the protein-coding, 2-3% of the genome carry the 97-98% as a mere passenger and neutral "cargo" on the evolutionary path, or does the latter have biological function? On one side of the debate, many commentaries have referred to the non-coding portion of the genome as "selfish" or "junk" DNA (Orgel and Crick, 1980), while on the other side, authors have argued that it contains the real blueprint for organismal development (Penman, 1995; Mattick, 2003), and the mechanisms of developmental complexity. Thus, this question could be referred to without much exaggeration as the most important issue in genetics today.


Rehabilitation training combined acupuncture for limb hemiplegia caused by cerebral hemorrhage: A protocol for a systematic review of randomized controlled trial.
Previous studies have reported that rehabilitation training combined acupuncture (RTA) can be used for the treatment of limb hemiplegia (LH) caused by cerebral hemorrhage (CH). However, its effectiveness is still unclear. In this systematic review study, we aim to evaluate the effectiveness and safety of RTA for LH following CH. We will retrieve the databases of CENTRAL, EMBASE, MEDILINE, CINAHL, AMED, CBM, and CNKI from inception to March 1, 2019 with no language restrictions. The randomized controlled trials of RTA for evaluating effectiveness and safety in patients with LH following CH will be included. Cochrane risk of bias tool will be used to measure the methodological quality for all included studies. Two authors will independently select the studies, extract the data, and assess the methodological quality of included studies. A third author will be invited to discuss if any disagreements exist between 2 authors. If more than 2 eligible studies will be included, the outcome data will be pooled, and meta-analysis will be conducted if it is possible. This systematic review will assess the effectiveness and safety of RTA for LH caused by CH. The primary outcome includes limbs function. The secondary outcomes consist of muscle strength, muscle tone, quality of life, and any adverse events. The findings of this study will summarize the current evidence of RTA for LH caused by CH, and may provide helpful evidence for the clinical treatment. The results of this study will be published in peer-reviewed journals or will be presented on conference meeting. This work does not require ethic approval, because it will be conducted based on the published studies. PROSPERO CRD42019120034.


Near-field investigation of the explosive dispersal of radioactive material based on a reconstructed spherical blast-wave flow.
A "dirty bomb" is a type of radiological dispersal device (RDD) that has been the subject of significant safety and security concerns given the disruption that would result from a postulated terrorist attack. Assessing the risks of radioactive dose in a hypothetical scenario requires models that can accurately predict dispersion in a realistic environment. Modelling a RDD is complicated by the fact that the most important phenomena occur over vastly disparate spatial and temporal length scales. Particulate dispersion in the air is generally considered on scales of hundreds to thousands of meters, and over periods of minutes and hours. Dispersion models are extremely sensitive, however, to the particle size and source characterization, which are determined in distances measured in micrometers to meters, over milliseconds or less. This study examines the extent to which the explosive blast determines the transport of contaminant particles relative to the atmospheric wind over distances relevant to "near-field" dispersion problems (i.e., hundreds of meters), which are relevant to urban environments. Our results indicate that whether or not the effect of the blast should be included in a near-field dispersion model is largely dependent on the size of the contaminant particle. Relatively large particles (i.e., >40 μm in diameter), which are most likely to be produced by a RDD, penetrate the leading shock front, thereby avoiding the reverse blast wind. Consequently, they travel much farther than suspended aerosols (<10 μm) before approaching the ambient wind velocity. This suggests that, for these "near-field" dispersion problems in urban environments, the transport of contaminants from the blast wave may be integral to accurately predicting their dispersion.


Obesity Genes, Personalized Medicine, and Public Health Policy.
The personalized medicine movement-also known as precision medicine and personalized genomics-has embraced the belief that genetic risk information can be used to motivate healthier choices and meaningful behaviour change. While a genuinely exciting area of research, there are numerous policy issues associated with a focus on the use of genetic risk information to personalize approaches to obesity prevention.


Thorough QT/QTc Evaluation of the Cardiac Safety of Secnidazole at Therapeutic and Supratherapeutic Doses in Healthy Individuals.
SYM-1219, a novel oral granule formulation of secnidazole, is under development as single-dose treatment for bacterial vaginosis. This 4-way, randomized, crossover study evaluated the effects of SYM-1219 on electrocardiographic (ECG) parameters in 52 healthy subjects. Subjects were administered single doses of SYM-1219, 2 g (proposed therapeutic dose), 6 g (supratherapeutic dose), placebo, and moxifloxacin (positive control). Serial digital 12-lead ECGs were recorded pre- and postdose; blood samples were taken to determine plasma secnidazole concentrations. A high-precision QT technique measured ECGs. The primary end point was change from baseline QTcF (∆QTcF); data were analyzed with the objective of excluding QT effects >10 milliseconds at postdosing time points and with exposure-response analysis. Safety and tolerability were assessed. Single doses of 2 g and 6 g SYM-1219 did not have a clinically relevant effect on the QTcF interval; an effect >10 milliseconds could be excluded at all postdosing time points. A shallow slope of the exposure-response relationship was seen (0.058 millisecond per μg/mL; 90%CI 0.042, 0.073); in this model, the effect on QTc can be predicted to be <10 milliseconds up to a secnidazole plasma concentration of ∼125 μg/mL, approximately 3.4-fold higher than anticipated peak therapeutic plasma levels. The moxifloxacin QT response demonstrated assay sensitivity. The most frequently reported treatment-emergent adverse events with SYM-1219 were headache, dizziness, and nausea. This thorough QT study demonstrated that SYM-1219 in doses and plasma concentrations up to 3-fold above therapeutically relevant levels does not have a clinically concerning effect on ECG parameters, including the QT interval.


Rhizobial root hair infection requires auxin signaling.
Legumes can enter into a mutualistic relationship with nitrogen-fixing rhizobacteria. A recent study by A. Breakspear et al. sheds new light on the mechanisms involved in rhizobial infection of their host root hair during symbiosis establishment and reveals a new role for auxin signaling in this process.


Control of eukaryotic membrane fusion by N-terminal domains of SNARE proteins.
SNARE proteins function at the center of membrane fusion reactions by forming complexes with each other via their coiled-coil domains. Several SNAREs have N-terminal domains (NTDs) that precede the coiled-coil domain and have critical functions in regulating the fusion cascade. This review will highlight recent findings on NTDs of syntaxins, the longin domain of VAMP proteins and SNAP-23/25 homologues in yeast. Biochemical and genetic experiments as well as the resolution of several NMR and crystal structures of SNARE NTDs shed light on their diverse function.


Helium3 polarization using spin exchange technique: application to simultaneous pulmonary ventilation/perfusion imaging in small animals.
To develop a simple and robust helium3 polarization system dedicated to small animal imaging. To demonstrate the potential of helium3 imaging for pulmonary ventilation and perfusion studies. A home-built polarization system based on spin-exchange technique was used. This system was applied for magnetic resonance imaging ventilation studies on rats using a 2-T magnet. Projection-reconstruction sequences combined with the sliding-window technique were used for acquisition of high temporal resolution ventilation images. Helium3 polarization levels up to 25% were obtained. Simultaneous ventilation and lung perfusion images were acquired with intravenous injection of superparamagnetic contrast agents. Dose effects were investigated using several contrast agent concentration values. A tabletop helium3 polarization system was realized. This equipment, which is easy to operate, allows the production of polarized gas appropriate to the requirements of small animal studies. This polarization system was used successfully on a ventilation/perfusion imaging study using intravascular contrast agent.


Neck pain causes respiratory dysfunction.
This paper describes a presumptive mechanism for the development of changes in respiratory function due to chronic neck pain. The patient with neck pain presents a number of factors that could constitute a predisposition of leading to a respiratory dysfunction: (a) the decreased strength of deep neck flexors and extensors, (b) the hyperactivity and increased fatigability of superficial neck flexors, (c) the limitation of range of motion, (d) the decrease in proprioception and disturbances in neuromuscular control, (e) the existence of pain and (f) the psychosocial influence of dysfunction. The possible connection of neck pain and respiratory function could have a great impact on various clinical aspects notably patient assessment, rehabilitation and pharmacological prescription.


NPSR1 gene is associated with reduced risk of rheumatoid arthritis.
Neuropeptide S receptor 1 (NPSR1) is a G protein-coupled receptor involved in immune response and is associated with several inflammatory diseases. We investigated the possible contribution of several polymorphisms in the intronic region of NPSR1 to rheumatoid arthritis (RA). Genotyping of 7 single-nucleotide polymorphisms (SNP) was performed in a total of 1232 patients with RA and 983 healthy controls of Spanish white origin by real-time polymerase chain reaction technology, using the TaqMan 5'-allele discrimination assay. One out of the 7 SNP analyzed (rs740347) was associated with RA [p after Bonferroni correction (p(BNF)) = 1.2 × 10(-3), OR 0.73]. An association was also observed with rheumatoid factor-positive and shared epitope-positive RA (p(BNF) = 0.011, OR 0.73; p(BNF) = 0.037, OR 0.75, respectively). Our results show that variations in the NPSR1 intronic region are associated with low risk in patients with RA, supporting other evidence that this locus represents a common genetic factor in inflammatory diseases.


[What are the alternative criteria for fine needle aspiration biopsy of a thyroid nodule?].
To identify the clinical and paraclinical factors of thyroid nodule malignancy (in absence of ultrasound-guided fine needle aspiration biopsy data). This retrospective study was conducted on a cohort of 282 patients admitted for management of a thyroid nodule disease. All patients had undergone surgery and the specimen had been analyzed anatomically and pathologically. Forty-four patients had malignant disease. Epidemiological, clinical, and paraclinical data, as well as the anatomical and pathological characteristics of the specimen were collected for each patient. We showed that the epidemiological data (sex and age), the nodule's characteristics (consistency, irregularities of the edges and fixity to underlying structures, and size), the presence of adenopathies, signs of compression, and the presence of calcifications were the predictability criteria of malignant disease. However, the scintigraphic aspect, the echostructure, and the hormonal status were not significant. This study underscores that a relevant clinical and paraclinical analysis remains highly contributive in the presurgical identification of factors predictive of malignancy of a thyroid nodule, notably in countries where technological tools are not always available.


A combined chemical-physical treatment for herpes simplex lesions in guinea pigs.
Determination of the effectiveness of chemical treatments for Herpes simplex type 2 infections has generally relied on a reduction in the rate of mortality. A more natural progression of the disease is seen when non-progressive cutaneous lesions are induced. Treatment of characteristic cutaneous lesions with ultrasound alone, a cream compound designated Herpigon alone, or a combination of ultrasound and Herpigon were compared to determine the time required for lesions to heal and the amount of virus recoverable from treated lesions. Results indicate that the use of Herpigon alone or in combination with ultrasound resulted in a significant reduction in the time required for the lesions to heal. A comparison of the amount of virus present in treated lesions indicated that the combined treatment was most effective in reducing the amount of recoverable virus.


[Measurement of the results of functional treatment of metatarsal fractures using the AOFAS scale and the duration of work incapacity].
To demonstrate the effectiveness of functional treatment for the fractures of the metatarsal, which consisted of immediate or early weight bearing without immobilisation. We prospectively studied 276 patients with simple or complex fractures of the metatarsal, treated with a functional method which consisted of immediate (before the 3(rd) day since the fracture) or early (between 3(rd) and 21(st) day) effective weight bearing. Inclusion criteria were patients aged 16-65, both sexes, diagnosed with isolated or multiple, closed or opened type I metatarsal fractures who did weight bearing exercises during the first 21 days. We analysed the effects of the steroid injection proposed for this treatment in the focus of the fracture, the days of weight bearing, rehabilitation and number of metatarsal fractures. Results were evaluated using AOFAS (American Orthopaedic Foot and Ankle Society) scores, days of work incapacity and complications of the treatment. The AOFAS score for patients treated functionally was excellent and we found few complications with it. The functional method is based on the function of ligaments and muscles of the forefoot and the aid of a rigid-soled shoe which allows early weight-bearing to avoid secondary displacement of the fractures. The results show that immediate weight bearing provides better results than delayed bearing. Injection of steroid does not appear to have any benefit. We propose the functional method for all closed displaced or non-displaced metatarsal fractures, except for the displaced fractures on the base of the fifth metatarsal.


Effect of Apatinib plus melatonin on vasculogenic mimicry formation by cancer stem cells from breast cancer cell line.
Vasculogenic mimicry (VM) is one of the most important causes of breast cancer metastasis and resistance against drugs. The cancer stem cells (CSCs) are known as essential factors for VM formation. In this study, the effects of melatonin, Apatinib, and a combination of Apatinib/melatonin on VM formation were investigated by breast CSCs from breast cancer cell line. The percentage of CSCs was determined in two breast cancer cell lines (MCF-7 and MDA-MB-231) by flow cytometry. The effects of Apatinib, melatonin, and a combination of Apatinib/melatonin were evaluated on proliferation and viability, migration and invasion, apoptosis, and VM formation in MDA-MB-231 cells. Moreover, expression levels of the involved proteins in cancer cell proliferation and viability, CSCs, migration and invasion, and VM formation were evaluated by real-time polymerase chain reaction (RT-PCR) and western blotting methods. Results of the present study showed that melatonin and Apatinib reduced survival rate of CSCs in a dose- and time-dependent manner. Apatinib, melatonin, and a combination of Apatinib/melatonin inhibited proliferation of breast CSCs (P ≤ 0.001). Formation of VM was decreased in the MDA-MB-231 cancer cell line treated with Apatinib and combination of Apatinib/melatonin. Apatinib and combination of Apatinib/melatonin reduced invasion of breast CSCs (P ≤ 0.0001). Expression of vascular endothelial VE-cadherin, ephrinA2 receptor (EPHA2), p-PI3K/phosphoinositide-3 kinase (PI3K) and phospho-AKT (p-AKT)/AKT ratios was decreased under the influence of Apatinib and a combination of Apatinib/melatonin (P ≤ 0.01). Apatinib or a combination of Apatinib/melatonin may be used to manage patients with breast cancer. However, further studies are needed to identify anti-cancer mechanisms of melatonin and Apatinib for better management of the patients with breast cancer.


Functionalized gold nanoparticle supported sensory mechanisms applied in detection of chemical and biological threat agents: a review.
There is a great necessity for development of novel sensory concepts supportive of smart sensing capabilities in defense and homeland security applications for detection of chemical and biological threat agents. A smart sensor is a detection device that can exhibit important features such as speed, sensitivity, selectivity, portability, and more importantly, simplicity in identifying a target analyte. Emerging nanomaterial based sensors, particularly those developed by utilizing functionalized gold nanoparticles (GNPs) as a sensing component potentially offer many desirable features needed for threat agent detection. The sensitiveness of physical properties expressed by GNPs, e.g. color, surface plasmon resonance, electrical conductivity and binding affinity are significantly enhanced when they are subjected to functionalization with an appropriate metal, organic or biomolecular functional groups. This sensitive nature of functionalized GNPs can be potentially exploited in the design of threat agent detection devices with smart sensing capabilities. In the presence of a target analyte (i.e., a chemical or biological threat agent) a change proportional to concentration of the analyte is observed, which can be measured either by colorimetric, fluorimetric, electrochemical or spectroscopic means. This article provides a review of how functionally modified gold colloids are applied in the detection of a broad range of threat agents, including radioactive substances, explosive compounds, chemical warfare agents, biotoxins, and biothreat pathogens through any of the four sensory means mentioned previously.


miR-4319 Suppresses the Growth of Esophageal Squamous Cell Carcinoma Via Targeting NLRC5.
The functions of microRNAs (miRNAs) in cancer progression have been recognized in recent years. However, the role of miR-4319 in esophageal squamous cell carcinoma (ESCC) remains unclear. We aimed to investigate the biological roles of miR-4319 in ESCC progression and the associated mechanisms. Real-time PCR was performed to examine the levels of miR-4319 in ESCC cell lines. The effects of miR-4319 and NOD-like receptor (NLR) family, caspase activation and recruitment domain (CARD) domain containing 5 (NLRC5) on cell proliferation and cell cycle progression were evaluated using MTT assay, colony formation and flow cytometry assays. Bioinformatics techniques and luciferase reporter assay were applied to validate NLRC5 as a miR-4319 target. The miR-4319 expression was lower in ESCC cells than in the normal cell line. The expression of miR-4319 repressed cell growth and induced cell cycle arrest. NLRC5 was validated as a direct downstream target of miR-4319. Overexpression of NLRC5 potentiated the effects of miR-4319 on cell growth and cell cycle distribution. Our results demonstrated that miR-4319 might function as a tumor suppressor by targeting NLRC5 in ESCC.


Plasticity and artificial selection for developmental mode in a poecilogonous sea slug.
The contribution of phenotypically plastic traits to evolution depends on the degree of environmental influence on the target of selection (the phenotype) as well as the underlying genetic structure of the trait and plastic response. Likewise, maternal effects can help or hinder evolution through affects to the response to selection. The sacoglossan sea slug Alderia willowi exhibits intraspecific variation for developmental mode (= poecilogony) that is environmentally modulated with populations producing more yolk-feeding (lecithotrophic) larvae during the summer, and more planktonic-feeding (planktotrophic) larvae in the winter. I found significant family-level variation in the reaction norms between 17 maternal families of A. willowi when reared in a split-brood design in low (16 ppt) versus high (32 ppt) salinity, conditions which mimic seasonal variation in salinity of natural populations. I documented a significant response to selection for lecithotrophic larvae in high and low salinity. The slope of the reaction norm was maintained following one generation of selection for lecithotrophy. When the maternal environment was controlled in the laboratory, I found significant maternal effects, which reduced the response to selection. These results suggest there is standing genetic variation for egg-mass type in A. willowi, but the ability of selection to act on that variation may depend on the environment in which the phenotype is expressed in preceding generations.


A kinetic model of the cyclin E/Cdk2 developmental timer in Xenopus laevis embryos.
Early cell cycles of Xenopus laevis embryos are characterized by rapid oscillations in the activity of two cyclin-dependent kinases. Cdk1 activity peaks at mitosis, driven by periodic degradation of cyclins A and B. In contrast, Cdk2 activity oscillates twice per cell cycle, despite a constant level of its partner, cyclin E. Cyclin E degrades at a fixed time after fertilization, normally corresponding to the midblastula transition. Based on published data and new experiments, we constructed a mathematical model in which: (1) oscillations in Cdk2 activity depend upon changes in phosphorylation, (2) Cdk2 participates in a negative feedback loop with the inhibitory kinase Wee1; (3) cyclin E is cooperatively removed from the oscillatory system; and (4) removed cyclin E is degraded by a pathway activated by cyclin E/Cdk2 itself. The model's predictions about embryos injected with Xic1, a stoichiometric inhibitor of cyclin E/Cdk2, were experimentally validated.


The cryosurgical treatment of intraepithelial neoplasia.
At the Finseninstituttet and the Radium Centre in Copenhagen, from 1971-1975 inclusive, cryosurgery was carried out altogether 59 times on 57 patients. Only 8 patients showed histopathological changes in the biopsies sufficient to indicate conization. Hysterectomy was carried out on 8 patients. In 7 of these the removed uteri showed either no malignant changes or changpy. Invasive growth was discovered only in 1 patient, who later underwent a total hysterectomy by the Wertheim method. A biopsy on 1 patient with carcinoma in situ, suspected invasive growth, was treated with radium.