Cannabinoid receptor type-2 stimulation, blockade, and deletion alter the vascular inflammatory responses to traumatic brain injury.
Immunomodulatory therapies have been identified as interventions for secondary injury after traumatic brain injury (TBI). The cannabinoid receptor type-2 (CB2R) is proposed to play an important, endogenous role in regulating inflammation. The effects of CB2R stimulation, blockade, and deletion on the neurovascular inflammatory responses to TBI were assessed. Wild-type C57BL/6 or CB2R knockout mice were randomly assigned to controlled cortical impact (CCI) injury or to craniotomy control groups. The effects of treatment with synthetic, selective CB2R agonists (0-1966 and JWH-133), a selective CB2R antagonist, or vehicle solution administered to CCI groups were assessed at 1-day after injury. Changes in TNF-α, intracellular adhesion molecule (ICAM-1), inducible nitric oxide synthase (iNOS), macrophage/microglial ionized calcium-binding adaptor molecule, and blood-brain-barrier (BBB) permeability were assessed using ELISA, quantitative RT-PCR, immunohistochemistry, and fluorometric analysis of sodium fluorescein uptake. CB2R knockouts and wild-type mice with CCI injury were treated with a CB2R agonist or vehicle treatment. TNF-α mRNA increased at 6 hours and 1 to 3 days after CCI; a CB2R antagonist and genetic knockout of the CB2R exacerbated TNF-α mRNA expression. Treatment with a CB2R agonist attenuated TNF-α protein levels indicating post-transcriptional mechanisms. Intracellular adhesion molecule (ICAM-1) mRNA was increased at 6 hours, and at 1 to 2 days after CCI, reduced in mice treated with a CB2R agonist, and increased in CB2R knockout mice with CCI. Sodium fluorescein uptake was increased in CB2R knockouts after CCI, with and without a CB2R agonist. iNOS mRNA expression peaked early (6 hours) and remained increased from 1 to 3 days after injury. Treatment with a CB2R agonist attenuated increases in iNOS mRNA expression, while genetic deletion of the CB2R resulted in substantial increases in iNOS expression. Double label immunohistochemistry confirmed that iNOS was expressed by macrophage/microglia in the injured cortex. Findings demonstrate that the endogenous cannabinoid system and CB2R play an important role in regulating inflammation and neurovascular responses in the traumatically injured brain. CB2R stimulation with two agonists (0-1966 and JWH-133) dampened post-traumatic inflammation, while blockade or deletion of the CB2R worsened inflammation. Findings support previous evidence that modulating the CB2R alters infiltrating macrophages and activated resident microglia. Further investigation into the role of the CB2R on specific immune cell populations in the injured brain is warranted.


Longitudinal imaging: change and causality.
Longitudinal studies that use MRI scans performed over multiple time-points have been increasingly employed in the study of different neurological disorders, including degenerative dementia, multiple sclerosis, and epilepsy. Although it is well established that increased rates of brain atrophy occur in degenerative dementia and multiple sclerosis, recent data have further described these changes and demonstrated that they correlate with both cognitive and functional decline. Advanced voxel-level techniques have also provided detailed descriptions of regional patterns of change, and a few studies have started to investigate changes over multiple MRI enabling the trajectories of brain loss over time to be determined. Researchers have also started to more thoroughly investigate the underlying causes of brain atrophy. Correlations have been observed between rate of brain atrophy and the presence of abnormal protein deposits in the brain in dementia, and the lesion burden in multiple sclerosis. However, longitudinal studies on epilepsy have been inconsistent, with very little recent data. Recent data further support the suggestion that longitudinal MRI provides a good biomarker of disease progression in dementia and multiple sclerosis, though more work needs to be performed to define the role of longitudinal imaging in epilepsy.


Ruptured abdominal aortic aneurysm with fistula into the right iliac vein.
Arteriovenous fistula between major abdominal vessels is an unusual complication of ruptured abdominal aortic aneurysm. It most frequently occurs between the aorta and the inferior vena cava, however, it is rare when occurring between the aorta and iliac veins. A case of an arteriovenous fistula (AVF), secondary to erosion of an arteriosclerotic abdominal aortic aneurysm into both the retroperitoneum and the iliac vein is presented. The literature is reviewed and the symptoms and the treatment are discussed.


Effects of mitragynine from Mitragyna speciosa Korth leaves on working memory.
Mitragyna speciosa Korth from Rubiaceae family is a tropical plant indigenous to Southeast Asia particularly in Thailand, Peninsular of Malaysia and Indonesia. The leaves have been used by natives for their opium-like effect and cocaine-like stimulant ability to combat fatigue and enhance tolerance to hard work. However there is no scientific information about the effect of mitragynine on the cognitive performances. This study is designed to examine the working memory effects of mitragynine which is extracted from Mitragyna speciosa mature leaves. The cognitive effect was studied using object location task and the motor activity in open-field test. Mitragynine 5, 10 and 15 mg/kg and were administered by intraperitoneal (IP) for 28 consecutive days and evaluated on day 28 after the last dose treatment. Scopolamine was used as the control positive drug. In this study there is prominent effects on horizontal locomotor activity was observed. Mitragynine significantly reduced locomotor activity in open-field test compared with vehicle. In object location task mitragynine (5, 10 and 15 mg/kg) did not showed any significances discrimination between the object that had changed position than the object that had remain in a constant position. Our results suggest that chronic administration of mitragynine can altered the cognitive behavioral function in mice.


Commentary on "Patients as 'subjects' or 'objects'
I believe that the main policies that should be stressed in situations involving trainees in patient care are: 1) there must be good supervision of the trainees; and 2) there must be openness in responding to patient questions as to what parts of a procedure will be done by trainees and how experienced the trainees may be. I do not agree with the authors that every part of every procedure or overall treatment conducted by residents or interns needs to be described to every patient and that patients' permission must be sought for each arrangement.


The Food Bank and Food Pantries Help Food Insecure Participants Maintain Fruit and Vegetable Intake During COVID-19.
Charitable food services, including food banks and pantries, support individual and households' food access, potentially maintaining food security and diet quality during emergencies. During the COVID-19 pandemic, the use of food banks and pantries has increased in the US. Here we examine perceptions of food banks and food pantries and their relationship to food security and fruit and vegetable (FV) intake during the first 6 months of the COVID-19 pandemic, using a statewide representative survey (n = 600) of residents of Vermont. The utilization of food pantries was more common among food insecure households and households with children. Among food insecure respondents, those who did not use a food pantry were significantly more likely to report consuming less FV during the pandemic. Further, we find respondents who are food insecure and using a food pantry report consuming more FV since the onset of the COVID-19 pandemic. We found that respondents who were both food insecure and reported not using a food pantry were significantly more likely to report both a reduction in fruit consumption (b = -0.58; p = 0.001) and a reduction in vegetable consumption (b = -0.415; p = 0.012). These results indicate that these services may support food access and one important dimension of diet quality (FV intake) for at-risk populations during emergencies.


Functional water flow pathways and hydraulic regulation in the xylem network of Arabidopsis.
In vascular plants, the xylem network constitutes a complex microfluidic system. The relationship between vascular network architecture and functional hydraulic regulation during actual water flow remains unexplored. Here, we developed a method to visualize individual xylem vessels of the 3D xylem network of Arabidopsis thaliana, and to analyze the functional activities of these vessels using synchrotron X-ray computed tomography with hydrophilic gold nanoparticles as flow tracers. We show how the organization of the xylem network changes dynamically throughout the plant, and reveal how the elementary units of this transport system are organized to ensure both long-distance axial water transport and local lateral water transport. Xylem vessels form distinct clusters that operate as functional units, and the activity of these units, which determines water flow pathways, is modulated not only by varying the number and size of xylem vessels, but also by altering their interconnectivity and spatial arrangement. Based on these findings, we propose a regulatory model of water transport that ensures hydraulic efficiency and safety.


Profound Sinoatrial Arrest Associated with Ibrutinib.
Ibrutinib is a Bruton's tyrosine kinase (BTK) inhibitor approved for second-line treatment for mantle cell lymphoma (MCL), chronic lymphocytic leukemia (CLL), and Waldenström macroglobulinemia. Ibrutinib use has been linked to increased incidence of atrial fibrillation and hypertension in multiple studies. Other forms of cardiac toxicities have also been reported in isolated case reports. Bradycardia and asystole have not been associated with ibrutinib use in the past. We present a case of a 76-year-old female with no prior cardiac history, who initiated treatment with ibrutinib for relapsing mantle cell lymphoma and was noted to have symptomatic bradycardia, greater than 20 second long pauses on her cardiac monitor requiring placement of a permanent pacemaker. This is the first case associating bradycardia and asystole with tyrosine kinase inhibitor use. Irreversible inhibition of certain cardioprotective tyrosine kinases has been a growing topic of research in oncology therapeutics.


Yield, quality and biochemical properties of various strawberry cultivars under water stress.
Although strawberry (Fragaria x ananassa Duch.) species are sensitive to abiotic stress conditions, some cultivars are known to be tolerant to different environmental conditions. We examined the response of different strawberry cultivars to water stress conditions in terms of yield, quality and biochemical features. The trial was conducted under two different irrigation regimes: in grow bags containing cocopeat (control, 30%; water stress, 15% drainage) with four different cultivars (Camarosa, Albion, Amiga and Rubygem). Fruit weight declined by 59.72% and the yield per unit area by 63.62% under water stress conditions as compared to control. Albion and Rubygem were found to be more tolerant and Amiga the most sensitive in terms of yield under stress conditions. Water stress increased all biochemical features in fruits such as total phenol, total anthocyanin, antioxidant activity and sugar contents. Among the cultivars, glucose and fructose was higher in Albion. Considering the rise in global warming, identification of resistant and tolerant cultivars to stress conditions are crucial for future breeding programmes. Our results showed that some of the fruit's physical features were affected negatively by stress conditions whereas many of the biochemical features such as total anthocyanin content, total phenolic content and antioxidant activity were positively modulated. © 2017 Society of Chemical Industry.


Bacillus licheniformis SA03 Confers Increased Saline-Alkaline Tolerance in Chrysanthemum Plants by Induction of Abscisic Acid Accumulation.
Soil saline-alkalization is a major abiotic stress that leads to low iron (Fe) availability and high toxicity of sodium ions (Na+) for plants. It has recently been shown that plant growth promoting rhizobacteria (PGPR) can enhance the ability of plants to tolerate multiple abiotic stresses such as drought, salinity, and nutrient deficiency. However, the possible involvement of PGPR in improving saline-alkaline tolerance of plants and the underlying mechanisms remain largely unknown. In this study, we investigated the effects of Bacillus licheniformis (strain SA03) on the growth of Chrysanthemum plants under saline-alkaline conditions. Our results revealed that inoculation with SA03 alleviated saline-alkaline stress in plants with increased survival rates, photosynthesis and biomass. The inoculated plants accumulated more Fe and lower Na+ concentrations under saline-alkaline stress compared with the non-inoculated plants. RNA-Sequencing analyses further revealed that SA03 significantly activated abiotic stress- and Fe acquisition-related pathways in the stress-treated plants. However, SA03 failed to increase saline-alkaline tolerance in plants when cellular abscisic acid (ABA) and nitric oxide (NO) synthesis were inhibited by treatment with fluridone (FLU) and 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (c-PTIO), respectively. Importantly, we also found that NO acted downstream of SA03-induced ABA to activate a series of adaptive responses in host plants under saline-alkaline stress. These findings demonstrated the potential roles of B. licheniformis SA03 in enhancing saline-alkaline tolerance of plants and highlighted the intricate integration of microbial signaling in regulating cellular Fe and Na+ accumulation.


Major vessel venous thrombosis in patients of posttubercular chronic constrictive pericarditis undergoing pericardectomy: A rare scenario.
We are reporting two cases of neck and arm major venous thrombosis in patients of posttubercular chronic constrictive pericarditis posted for pericardectomy. There was unanticipated difficulty in placement of Internal Jugular vein catheter and subsequent ultrasound revealed thrombosis in the major veins. It was not diagnosed in the preoperative period. This report raises this major complication and highlights the use of ultrasound in such scenarios.


Coagulation abnormalities associated with extensive venous malformations of the limbs: differentiation from Kasabach-Merritt syndrome.
Confusion in the nomenclature of vascular malformations has been a major obstacle to the understanding of these conditions, so that misdiagnosis and treatment inconsistencies are common. Coagulation abnormalities occurring in combination with venous malformations (VM) have been misdiagnosed as Kasabach-Merritt syndrome (KMS), despite marked differences in clinical features, pathology and treatment. A homogenous group of 24 patients with diffuse limb VM was entered into a retrospective chart review study. The VM affected an upper limb in 12 patients, a lower limb in 10 and both in two. Localized intravascular coagulation (LIC) was characterized by a decrease in fibrinogen (0.5-1 g/l), an increase in d-dimers (2-64 micro g/ml) and presence of soluble complex of fibrin (+ to +++). Platelet counts were normal or slightly decreased. Higher VM severity scores were associated with more severe LIC. A number of events such as sclerotherapy, surgery, bone fracture, prolonged immobilization and pregnancy or menstruation triggered conversion of the LIC to disseminated intravascular coagulation (DIC), with bleeding related to factor consumption and multiorgan failure related to disseminated microvascular thrombosis. Clinical symptoms associated with worsening of LIC were pain, thrombosis and bleeding at wound sites or during surgery. None of the patients had the large ecchymotic and inflammatory tumours seen in KMS. Graded permanent elastic compression with heparin therapy was the only effective treatment. In conclusion, VM-associated LIC is a distinctive lifelong coagulopathy that must be differentiated from KMS, which is characterized by platelet trapping within a vascular tumour of infancy. The treatment of the two conditions is very different.


The other half of the whole: teaching patients to communicate with physicians.
A wide body of research suggests that the nature of communication between patients and physicians is strongly related to health outcomes. Interventions that involve teaching patients to communicate with physicians are important to assess in this context. We conducted a review of randomized controlled trials (RCTs) in the outpatient setting from 1975 to 2000. Patient communication interventions were classified as high, medium, or low intensive, depending on the length of the intervention, use of personnel, and estimated cost. Characteristics of 16 studies were examined, including sample populations, types of interventions, and the nature of health outcomes. Patient improvement in a variety of outcomes as a result of communication training was demonstrated. Positive change variables included patient communication, medical outcomes, functional status, and adherence to treatment. Studies revealed mixed findings on the outcome of patient satisfaction. All US studies suggested that pre-visit training had no effect on the overall length of the medical visit. Studies indicated improvement in a variety of patient outcomes. However, the wide variation in study design, interventions, and outcomes hinders the ability to draw well-founded conclusions. Future research needs to further address biopsychosocial outcomes, cost-effectiveness, and their relationship.


Comparison of serum beta 2-microglobulin and carcinoembryonic antigen (CEA) in the follow-up of breast cancer patients.
Using commercially available radioimmune test kits, serial determinations of serum beta 2-microglobulin and CEA were performed in 337 patients, who had been treated for breast cancer by modified radical mastectomy and radiotherapy. The pre-therapeutic data indicated a higher incidence of pathological beta 2-microglobulin and CEA levels in patients with distant metastases than in patients with localized disease. However, this finding did not allow the conclusion of a direct complementarity of beta 2-microglobulin and CEA as tumour markers, since the group of patients with distant metastasis contained a high percentage of elderly patients who generally can be expected to have elevated beta 2-microglobulin serum concentrations. Therefore, the correlation of the clinical course of malignant disease and the incidence of relapses with the changes of serum beta 2-microglobulin and CEA concentrations was examined during the post-treatment surveillance: 7/9 cases (78%) with local recurrence and 46/73 cases (63%) with distant spread of disease were not indicated in the beta 2-microglobulin follow-up by pathologic serum concentrations, whereas in the CEA follow-up only 1/9 and 2/73 false negative indications were registered. The poor correlation suggests that serum beta 2-microglobulin is not directly tumour associated in breast cancer and does not fulfill the criteria of a tumour marker.


Organizational Support, Workload, and Intent to Stay: Work Environment Perceptions in Perianesthesia Nursing Units.
The purpose of this ASPAN study was to understand perianesthesia nurses' perception of their work environments in regards to organizational support, workload, intent to stay, and overall nurse satisfaction. A descriptive design was used with survey methodology. An online survey was sent to American Society of PeriAnesthesia Nurses members. The Individual Workload Perception Scale-Revised was used. A total of 2,121 American Society of PeriAnesthesia Nurses members participated (21% response rate). Fifty-three percent reported that their nurse manager had responsibilities for three or more units. Having an assigned preceptor had a significant difference with organizational support, workload, intent to stay, and overall nurse satisfaction. Certified nurses reported significantly better perceptions of workload and intent to stay. This is the first national glimpse of the perianesthesia work environment and its influence on nurse outcomes. These results can be used to improve the perianesthesia work environment.


Security deficiencies in psychiatric units and mental hospitals: what regulators are finding; how hospitals are responding.
There is probably no other healthcare environment more difficult to manage than a psychiatric facility. So reports Jim House of the Mental Health Association's St. Louis, MO, chapter. Patients--many of them estranged from their families--find it difficult to report complaints ... may not even realize the dangers they are in, he says. Conversely, mentally impaired patients can also voice irrational complaints, and make accusations that turn out to be unfounded ... but only after extensive investigative surveys by state agencies are conducted, and the facility's accreditation and state licensure are put at risk. In this report, we'll present examples of what happened at four facilities when state or federal investigators go in, or the hospital is subjected to negative media coverage.


Pneumothorax following thoracic radiation therapy for Hodgkin's disease.
Radiation therapy alone to the nodal drainage sites above the diaphragm, namely a "mantle" field, is often standard treatment for early stage Hodgkin's disease and may be used in combination with chemotherapy in more advance disease. Localised pneumonitis and fibrosis are recognised treatment related sequelae; however, other pulmonary complications, including pneumothorax, have been described. Two cases of spontaneous pneumothorax following mantle radiation therapy are presented.


DNA damage response, checkpoint activation and dysfunctional telomeres: face to face between mammalian cells and Drosophila.
Eukaryotic cells evolved telomeres, specialized nucleoproteic complexes, to protect and replicate chromosome ends. In most organisms, telomeres consist of short, repetitive G-rich sequences added to chromosome ends by a reverse transcriptase with an internal RNA template, called telomerase. Specific DNA-binding protein complexes associate with telomeric sequences allowing cells to distinguish chromosome ends from sites of DNA damage. When telomeres become dysfunctional, either through excessive shortening or due to defects in the proteins that form their structure, they trigger p53/pRb pathways that limits proliferative lifespan and eventually leads to chromosome instability. Drosophila lacks telomerase, telomeres are assembled in a sequence-independent fashion and their length is maintained by transposition of three specialized retroelements. Nevertheless, fly telomeres are maintained by a number of proteins involved in telomere metabolism as in other eukaryotic systems and that are required to prevent checkpoint activation and end-to-end fusion. Uncapped Drosophila telomeres induce a DNA damage response just as dysfunctional human telomeres. Most interestingly, uncapped Drosophila telomeres also activate the spindle assembly checkpoint (SAC) by recruiting the SAC kinase BubR1. Here we review parallelisms and variations between mammalian and Drosophila cells in the crosstalks between telomeres and cell cycle regulation.


The phosphotransferase system of Lactobacillus casei: regulation of carbon metabolism and connection to cold shock response.
Genome sequencing of two different Lactobacillus casei strains (ATCC334 and BL23) is presently going on and preliminary data revealed that this lactic acid bacterium possesses numerous carbohydrate transport systems probably reflecting its capacity to proliferate under varying environmental conditions. Many carbohydrate transporters belong to the phosphoenolpyruvate:sugar phosphotransferase system (PTS), but all different kinds of non-PTS transporters are present as well and their substrates are known in a few cases. In L. casei regulation of carbohydrate transport and carbon metabolism is mainly achieved by PTS proteins. Carbon catabolite repression (CCR) is mediated via several mechanisms, including the major P-Ser-HPr/catabolite control protein A (CcpA)-dependent mechanism. Catabolite response elements, the target sites for the P-Ser-HPr/CcpA complex, precede numerous genes and operons. PTS regulation domain-containing antiterminators and transcription activators are also present in both L. casei strains. Their activity is usually controlled by two PTS-mediated phosphorylation reactions exerting antagonistic effects on the transcription regulators: P~EIIB-dependent phosphorylation regulates induction of the corresponding genes and P~His-HPr-mediated phosphorylation plays a role in CCR. Carbohydrate transport of L. casei is also regulated via inducer exclusion and inducer expulsion. The presence of glucose, fructose, etc. leads to inhibition of the transport or metabolism of less favorable carbon sources (inducer exclusion) or to the export of accumulated non-metabolizable carbon sources (inducer expulsion). While P-Ser-HPr is essential for inducer exclusion of maltose, it is not necessary for the expulsion of accumulated thio-methyl-beta-D-galactopyranoside. Surprisingly, recent evidence suggests that the PTS of L. casei also plays a role in cold shock response.


Detection of dopamine neurotransmission in "real time".
Current imaging techniques have limited ability to detect neurotransmitters released during brain processing. It is a critical limitation because neurotransmitters have significant control over the brain activity. In this context, recent development of single-scan dynamic molecular imaging technique is important because it allows detection, mapping, and measurement of dopamine released in the brain during task performance. The technique exploits the competition between endogenously released dopamine and its receptor ligand for occupancy of receptor sites. Dopamine released during task performance is detected by dynamically measuring concentration of intravenously injected radiolabeled ligand using a positron emission tomography (PET) camera. Based on the ligand concentration, values of receptor kinetic parameters are estimated. These estimates allow detection of dopamine released in the human brain during task performance.


A review of guidelines for urinary tract infections in children younger than 2 years.
CME EDUCATIONAL OBJECTIVES: 1.Review recent guidelines for diagnosis and treatment of urinary tract infections in children younger than 2 years.2.Review recent recommendations for imaging children with urinary tract infection.3.Understand rationale for recent treatment recommendations and prophylaxis of children with urinary tract infection.


The impact of a change in commitment procedures on the character of involuntary psychiatric patients.
The statutory requirements for involuntary civil psychiatric confinement have become increasingly restrictive. In the jurisdiction under investigation, patients were originally admitted under an Order to Apprehend (OTA) procedure simply on the petition of two affiants who indicated the patient was in need of care. A newly elected judge instituted changes requiring affiants to claim the subject was "dangerous" to self or others and asking for a clinical assessment and recommendation before signing the petitioned request for involuntary confinement. It might be expected that the more restrictive procedures would have produced a population of more assaultive patients. A study of petitions signed under in the earlier (N = 133) and later, more restrictive (N = 218) procedures indicated that the proportion of assaultive or dangerous patients was virtually identical. Further investigation, using hospital data an OTA patients from this area in both time periods, suggested that while patients were not more assaultive, they appeared to be more seriously ill or psychiatrically impaired. Apparently, movement to a dangerousness standard that allows clinical discretion in interpreting its presence may result in involuntary commitments for more seriously ill, although not necessarily more assaultive, patients.


Intrinsic proclivity of left-handed conformation in large Nest motif peptides inferred from molecular dynamics.
The 'Nest' motif plays a functional role in protein owing to its ligand binding potential aided by geometric concavity. The presence of less favored left-handed conformation (L-state) in its structure makes this concavity possible and in shaping the native chemical environment amenable to stable binding interactions. To understand the persistent appearance of L-state torsion in the Nest motif, we analyzed 0.5μs Molecular Dynamics (MD) simulation trajectories of 35 six-residue peptides (out of a total of 50 large Nest sequences of ≥6 residues) identified in our previous study. Analysis of the MD trajectories of the individual peptides reveals initial L-state in 60% of the peptides persists for >40% of the trajectory. Further, Nests with different sequences appear to adopt a specific conformational state driven by the neighboring L-state residues. The sequences also possess short secondary structures and amino acid repeats, suggesting evolutionary conservation and the specific role of amino acids in locally predisposing the torsion angle to the L-state. These findings help us to understand how L-state conformation is an essential prerequisite in stabilizing the Nest motif and shed light on the sequence-structure-function paradigm in the rational design of peptides and peptidomimetics for therapeutics.Communicated by Ramaswamy H. Sarma.


Thrombospondin-1 as an endogenous inhibitor of angiogenesis and tumor growth.
Thrombospondin-1 (TSP-1) is a matricellular glycoprotein that influences cellular phenotype and the structure of the extracellular matrix. These effects are important components of the tissue remodeling that is associated with angiogenesis and neoplasia. The genetic mutations in oncogenes and tumor suppressor genes that occur within tumor cells are frequently associated with decreased expression of TSP-1. However, the TSP-1 that is produced by stromal fibroblasts, endothelial cells and immune cells suppresses tumor progression. TSP-1 inhibits angiogenesis through direct effects on endothelial cell migration and survival and through indirect effects on growth factor mobilization. TSP-1 that is present in the tumor microenvironment also acts to suppress tumor cell growth through activation of transforming growth factor beta in those tumor cells that are responsive to TGF beta. In this review, the molecular basis for the role of TSP-1 in the inhibition of tumor growth and angiogenesis is summarized.


[Study of hepatic function in patients with gastrointestinal anastomosis].
In 47 patients with gastric ulcer disease, the absorptive-excretive function of the liver after resection of the stomach was studied by means of bengal rosy radioactive (bengal-rose131I). All the patients examined demonstrated a decrease in the absorptive function of the liver, which was more pronounced in creation of Hofmeister-Finsterer anastomosis. In hepatography with the use of bengal-rose 131I, the insignificant disorders in the liver function were noted, which couldn't be detected by means of biochemical methods of investigation.


Effect of cinnamon essential oil on bacterial diversity and shelf-life in vacuum-packaged common carp (Cyprinus carpio) during refrigerated storage.
The present study investigated the effect of cinnamon essential oil on the quality of vacuum-packaged common carp (Cyprinus carpio) fillets stored at 4±1°C in terms of sensory scores, physicochemical characteristics (total volatile basic nitrogen (TVB-N), biogenic amines, and color), and presence of spoilage microbiota. A total of 290,753 bacterial sequences and 162 different genera belonging to 14 phyla were observed by a high-throughput sequencing technique targeting the V3-V4 region of 16S rDNA, which showed a more comprehensive estimate of microbial diversity in carp samples compared with microbial enumeration. Before storage, Macrococcus and Aeromonas were the prevalent populations in the control samples, but cinnamon essential oil decreased the relative abundance of Macrococcus in the treated samples. Variability in the predominant microbiota in different samples during chilled storage was observed. Aeromonas followed by Lactococcus were the major contaminants in the spoiled control samples. Microbial enumeration also observed relatively higher counts of Aeromonas than other spoilage microorganisms. Compared with the control samples, cinnamon essential oil inhibited the growth of Aeromonas and Lactococcus were the predominant components in the treated samples on day 10; plate counts also revealed a relatively high level of lactic acid bacteria during refrigerated storage. However, there were no significant differences (P>0.05) in the composition of dominant microbiota between these two treatments at the end of the shelf-life. Furthermore, cinnamon essential oil treatment was more effective in inhibiting the increase of TVB-N and the accumulation of biogenic amines (especially for putrescine and cadaverine levels). Based primarily on sensory analysis, the use of cinnamon essential oil extended the shelf-life of vacuum-packaged common carp fillets by about 2days.


One Peptide Reveals the Two Faces of α-Helix Unfolding-Folding Dynamics.
The understanding of fast folding dynamics of single α-helices comes mostly from studies on rationally designed peptides displaying sequences with high helical propensity. The folding/unfolding dynamics and energetics of α-helix conformations in naturally occurring peptides remains largely unexplored. Here we report the study of a protein fragment analogue of the C-peptide from bovine pancreatic ribonuclease-A, RN80, a 13-amino acid residue peptide that adopts a highly populated helical conformation in aqueous solution. 1H NMR and CD structural studies of RN80 showed that α-helix formation displays a pH-dependent bell-shaped curve, with a maximum near pH 5, and a large decrease in helical content in alkaline pH. The main forces stabilizing this short α-helix were identified as a salt bridge formed between Glu-2 and Arg-10 and the cation-π interaction involving Tyr-8 and His-12. Thus, deprotonation of Glu-2 or protonation of His-12 are essential for the RN80 α-helix stability. In the present study, RN80 folding and unfolding were triggered by laser-induced pH jumps and detected by time-resolved photoacoustic calorimetry (PAC). The photoacid proton release, amino acid residue protonation, and unfolding/folding events occur at different time scales and were clearly distinguished using time-resolved PAC. The partial unfolding of the RN80 α-helix, due to protonation of Glu-2 and consequent breaking of the stabilizing salt bridge between Glu-2 and Arg-10, is characterized by a concentration-independent volume expansion in the sub-microsecond time range (0.8 mL mol-1, 369 ns). This small volume expansion reports the cost of peptide backbone rehydration upon disruption of a solvent-exposed salt bridge, as well as backbone intrinsic expansion. On the other hand, RN80 α-helix folding triggered by His-12 protonation and subsequent formation of a cation-π interaction leads to a microsecond volume contraction (-6.0 mL mol-1, ∼1.7 μs). The essential role of two discrete side chain interactions, a salt bridge, and in particular a single cation-π interaction in the folding dynamics of a naturally occurring α-helix peptide is uniquely revealed by these data.


Endemic, epidemic and pandemic infections: the roles of natural and acquired herd immunity.
This review summarizes the general concepts of innate and acquired immunity, including vaccine use and hesitancy, as they relate to reduction of the global burden of highly communicable infectious diseases. Vaccination to increase herd immunity remains the cornerstone of disease prevention worldwide yet global vaccination goals are not being met. Modern obstacles to vaccine acceptance include hesitancy, reduced altruistic intentions, impact of COVID-19, distrust of science and governmental agencies as well as recent geopolitical and environmental disasters. Together, such barriers have negatively impacted immunization rates worldwide, resulting in epidemics and pandemics of serious life-threatening infections from vaccine-preventable diseases, especially those affecting children. In addition, pathogens thought to be controlled or eradicated are reemerging with new genetic traits, making them more able to evade natural and acquired immunity, including that induced by available vaccines. Lastly, many serious and widespread infectious diseases await development and utilization of efficacious vaccines. The global burden of communicable diseases remains high, necessitating continued pathogen surveillance as well as vaccine development, deployment and continued efficacy testing. Equally important is the need to educate aggressively the people and their leaders on the benefits of vaccination to the individual, local community and the human population as a whole.


Design of a Braille Learning Application for Visually Impaired Students in Bangladesh.
Visually impaired students (VIS) are unable to get visual information, which has made their learning process complicated. This paper discusses the overall situation of VIS in Bangladesh and identifies major challenges that they are facing in getting education. The Braille system is followed to educate blind students in Bangladesh. However, lack of Braille based educational resources and technological solutions have made the learning process lengthy and complicated for VIS. As a developing country, Bangladesh cannot afford for the costly Braille related technological tools for VIS. Therefore, a mobile phone based Braille application, "mBRAILLE", for Android platform is designed to provide an easy Braille learning technology for VIS in Bangladesh. The proposed design is evaluated by experts in assistive technology for students with disabilities, and advanced learners of Braille. The application aims to provide a Bangla and English Braille learning platform for VIS. In this paper, we depict iterative (participatory) design of the application along with a preliminary evaluation with 5 blind subjects, and 1 sighted and 2 blind experts. The results show that the design scored an overall satisfaction level of 4.53 out of 5 by all respondents, indicating that our design is ready for the next step of development.


The effects of dementia in the surgical patient.
Dementia is a progressive, degenerative disease of the brain that affects as many as 4 million Americans today. The risk of adverse events related to medical or surgical treatment is significant when even a mild cognitive impairment is not identified. An accurate diagnosis will facilitate a plan of care that will assure the patient's physical, emotional, and spiritual needs are met.


Methicillin-resistant Staphylococcus aureus, Samoa, 2007-2008.
Little is known about the epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) in most Pacific Island nations. Relatively high rates of MRSA have been reported in Polynesian people living outside the Pacific Islands. To determine the prevalence and characteristics of MRSA, we assessed wound swabs from 399 persons with skin and soft tissue infection living in Samoa. MRSA was isolated from 9% of study participants; 34 of the 196 S. aureus isolates were MRSA. Five MRSA genotypes were identified; the 3 most common were USA300, the Queensland clone, and a sequence type 1 MRSA strain that shares <85% homology with the sequence type 1 MRSA strain common in the region (WA MRSA-1). The Southwest Pacific MRSA clone was identified but accounted for only 12% of MRSA isolates. The high prevalence of MRSA in Samoa provides impetus for initiatives to improve antimicrobial drug resistance surveillance, infection control, and antimicrobial drug use in Pacific Island nations.


The Significance of Understanding Body Language in Depressed Patients within the Context of Creative Psychopharmacotherapy.
Since it is generally known that the human body is the best image of the human soul, this paper aims to explain how important body language is when diagnosing psychiatric diagnosis "depression". It is important to point out the importance of other alternative approaches in the treatment of depression when standard psychopharmacotherapy is not enough. Body language is a powerful form of non-verbal communication that provides important traces of intentions, emotions, and motivations in other people. In everyday life, we collect information about what people think and feel by their body posture, manners, and gestures. Evaluations of clinical depression are traditionally based on verbal information. However, non-verbal expressive behavior, related to reflexive feedback of a person, may reveal negative emotional or social processes that are not fully controlled by patients therapy, along with other artistic therapies (art therapy, drama therapy, and music therapy are other artistic therapies that are applied in Great Britain) offers an attractive opportunity for patients because it enables them to work on those issues that are placed on non-verbal and pre-verbal level. Creative psychofarmacotherapy is the concept that involves creativity as its main means. In this context, the importance of physical activity and body movements will be emphasized in the treatment of depression, when regular psychopharmacotherapy is not sufficient. To conclude, the patient has the right to actively take part in creating a therapeutic relationship and responsibly contributes to overcoming psychopathology. The importance of physical activities and body movements is emphasized in the treatment of depressive people. Studies have shown that the anti-depressive effect of physical activity is increased with simultaneous use of antidepressants, as well as that movement therapy and music therapy, together with regular pharmacotherapeutic methods, help with fast recovery and that they can be used in a creative approach to problem-solving.


Neonatal orbital abscess after sinus surgery: case report and brief review.
Orbital abscess formation in neonates is rare, with only 12 cases reported in the literature. We present a case of orbital cellulitis with orbital abscesses following repair of congenital choanal atresia in a 2-week-old neonate. This is the first reported case of an orbital abscess following a sinus procedure in a neonate.


Orlistat Displays Antitumor Activity and Enhances the Efficacy of Paclitaxel in Human Hepatoma Hep3B Cells.
Orlistat has been proved to be an effective fatty acid synthase inhibitor that is able to inhibit the proliferation and induce apoptosis in many cancer cell types. However, the anticancer effects of orlistat on hepatocellular carcinoma are undefined. We found that orlistat inhibited cell growth and induced G0/G1 cell cycle arrest with increased cyclin D, cyclin E, and p21 expression in human hepatoma Hep3B cells. Furthermore, protein expression of cyclin A, cyclin B, Cdk1, Cdk2, and Cdk4 was reduced by orlistat. This study investigated the role of lipid metabolism on orlistat-induced human hepatoma Hep3B cell death. The decrease in the expression of key enzymes in fatty acid metabolism, including FASN, ACOT8, PPT1, FABP1, CPT1 and CPT2, was observed after orlistat treatment. We also demonstrated that peroxisomal activity was involved in the orlistat-induced Hep3B cell death. In this study, we established an in vitro model to investigate the effect of orlistat on lipid accumulation. We found that orlistat significantly inhibited the cellular lipid content when administered in fatty acid overload conditions in Hep3B cells. Combination treatment of orlistat and paclitaxel was able to induce a synergistic effect on growth inhibition and cell apoptosis in Hep3B cells. Our data suggested that orlistat displays antitumor activity and enhances the efficacy of paclitaxel in Hep3B cells.


The ongoing quest for biomarkers in Ankylosing Spondylitis.
Ankylosing Spondylitis poses significant challenges in terms of early diagnosis, assessment of disease activity, predicting response to the treatment and monitoring radiographic progression. With better understanding of underlying immunopathogenesis, effective targeted therapies are available which improve symptoms, quality of life and possibly slow the radiographic progression. There has been a growing interest in the discovery of biomarkers for defining various aspects of disease assessment and management in Ankylosing Spondylitis. The C-reactive protein and HLA-B27 are most commonly used biomarkers. This review describes many other newer biomarkers which have potential clinical applications in this chronic inflammatory disease.


Network Anatomy Controlling Abrupt-like Percolation Transition.
We virtually dissect complex networks in order to understand their internal structure, just as doctors do with the bodies of animals. Our novel method classifies network links into four categories: bone, fat, cartilage, and muscle, based on network connectivity. We derive an efficient percolation strategy from this new viewpoint of network anatomy, which enables abrupt-like percolation transition through removal of a small amount of cartilage links, which play a crucial role in network connectivity. Furthermore, we find nontrivial scaling laws in the relationships between four types of links in each cluster and evaluate power exponents, which characterize network structures as seen in the real large-scale network of trading business firms and in the Erdős-Rényi network. Finally, we observe changes in the transition point for random bond percolation process, demonstrating that the addition of muscle links enhances network robustness, while fat links are irrelevant. These findings aid in controlling the percolation transition for an arbitrary network.


Update on new research in Gram-negative infections European Congress of Clinical Microbiology and Infectious Diseases 2017 (22-25 April, Vienna, Austria).
European Congress of Clinical Microbiology and Infectious Diseases 2017 (22-25 April, Vienna, Austria). Collaborative studies between hospitals in Europe and across the USA provided new insights into assessing susceptibility patterns and optimizing antimicrobial therapy in patients with infections caused by Gram-negative bacteria, including carbapenemase-producing Enterobacteriaceae (CPE) and Pseudomonas aeruginosa.


[Identification and characteristics of steroid hormone receptor binding properties in the nuclear fraction of human prostatic adenoma].
Steroid receptors in adenoma nuclear fraction of the human prostate were studied. Androgen and progestin receptors were revealed in 0.4 KCl nuclear extracts. The measured association constant values were 6.05 +/- 1.45 X 10(9) M-1 and 2.08 +/- 0.37 X 10(9) M-1 for 5 alpha-dihydrotestosterone and progesterone, respectively. Only 5 alpha-dihydrotestosterone and testosterone competed markedly with 3H-5 alpha-dihydrotestosterone, hormonal specificity of 3H-progesterone binding affinity being less pronounced. Specific estradiol binding being found in several adenomas was very low. Glucocorticoid receptors were not detected.


How technical change has boosted fish aggregation device productivity in the Indian Ocean tuna fishery.
Excess harvesting power can threaten the long-term sustainability of fisheries. Indicators of excess harvesting capacity must include input-output-based estimates of economic production efficiency. The increasing use of drifting Fish-Aggregating-Devices (DFADs) has boosted fishing productivity in high-seas tuna fisheries, perhaps beyond the biological capacity of the stocks, and is an object of global debate. We carried out a Data Envelopment Analysis (DEA) of relative changes in production efficiencies of the French purse-seine fleet targeting tropical tuna in the western Indian Ocean using two fishing strategies: (1) on floating objects (FOB) and (2) free swimming schools (FSC) using tuna catch and effort data spanning 1992-2019. We show that FOB fishing evolved dramatically through time with an estimated change of 3.6%yr-1 (8.0%yr-1 2007-2019), in contrast to 2.1%yr-1 for FSC. While the efficiency level in combining and using inputs has barely changed for FOB fishing, it means that all the growth in productivity comes from technical change for this strategy. The dynamics is different for the FSC with a mixture of innovation and higher efficiency. Immediate plans to improve input-based management in this region are needed to prevent further risks of overfishing to yellowfin (Thunnus albacares) and skipjack (Katsuwonus pelamis) tunas.


Application Value of Spectral CT Imaging in Quantitative Analysis of Early Lung Adenocarcinoma.
To investigate the clinical value of gemstone energy spectral CT imaging for the quantitative analysis of early lung adenocarcinoma. 76 cases of pulmonary ground-glass nodules pathologically confirmed as precancerous lesion and early lung cancer (including pure ground-glass nodules in 46 cases and mixed ground-glass nodules in 30 cases) underwent chest CT scan first and then underwent contrast-enhanced gemstone energy spectral CT to get arterial phase images, venous phase images, and delayed phase images. All the lesions were set the region of interest (ROI). Cases of the pure ground-glass nodule (pGGN) were measured at the maximum level of lesions, cases of the mixed ground-glass nodule (mGGN) were measured in two areas of ground-glass and solid components, CT value and iodine concentrations of lesions in three-phase scanning were separately measured, and at the same time, iodine concentrations of the thoracic aorta were also measured. The normalized iodine concentrations (NICs) were calculated, that is, the ratio of iodine concentrations of lesions and the thoracic aorta. CT values of lesions were also measured at each stage of 70 keV. All the quantitative data were expressed by the mean ± standard deviation, and paired t-test was used for pairwise comparison. In 76 cases, in the spectral CT imaging mode, the NIC value of solid components of the GGN was 0.33 ± 0.16 in the arterial phase (AP), 0.52 ± 0.25 in the venous phase (VP), and 0.58 ± 0.34 in the delayed phase (DP). There were significant differences of P values of NICs between each two phases in both solid component cases and the ground-glass component cases in AP/VP, VP/DP, and AP/DP (P < 0.05); there were no statistically significant P values of CT values between each two phases in three-period enhanced CT in both the solid component cases and the ground-glass component cases in AP/VP, VP/DP, and AP/DP (P > 0.05). Gemstone energy spectral CT with quantitative imaging can dynamically reflect the enhancement features of the pulmonary GGN.


[Extraintestinal Salmonella infections in four Danish counties. Inverse relationship between invasiveness and zoonotic serotypes].
The relationship between invasiveness and incidence of non-typhoid salmonellosis was ascertained retrospectively in a population of 1.9 million in four Danish counties during the three-year period 1992-1994. The study comprised 4175 cases diagnosed by culture either locally or at Statens Serum Institut, Copenhagen. Two hundred and forty-four patients had extraintestinal infections caused by 24 out of the total number of 101 different serotypes. Invasiveness ranged widely from 4% to > 90% for individual serotypes. Salmonella typhimurium and Salmonella enteritidis formed a high-incidence group (incidence rates > or = 25/100,000/year) compared to the remaining 22 serotypes (< 5/100,000/year). The low-incidence group was more invasive than the high-incidence group even when excluding Salmonella dublin, which is highly invasive, and including 212 cases of salmonelloses caused by serotypes isolated entirely from faeces (relative risk 1.54, 95% confidence limits 1.19 < RR < 2.00). The data corroborate a previous more limited study and indicate that previous exposure to salmonella and acquired immunity may play a role in the occurrence of extraintestinal non-typhoid salmonellosis.


A Randomized Comparison of Bougie-Assisted and TracheoQuick Plus Cricothyrotomies on a Live Porcine Model.
Cricothyrotomy is a rescue procedure in "cannot intubate, cannot oxygenate" scenarios where other methods of nonsurgical airway management have failed. We compared 2 cuffed cricothyrotomy sets, bougie-assisted cricothyrotomy (BACT) and novel percutaneous TracheoQuick Plus, on a live porcine model in a simulated periarrest situation. Thirty-four anesthetized minipigs were randomly allocated into two groups: BACT technique (n = 17) and TracheoQuick Plus (n = 17). The primary outcome was duration of cricothyrotomy while secondary outcomes were total success rate, number of attempts, location of incision, changes in heart rate, oxygen saturation, and the incidence of complications. BACT was significantly faster than TracheoQuick Plus cricothyrotomy, with a median time of 69 sec (IQR 56-85) versus 178 sec (IQR 152-272). The total success rate was without difference. 94% of BACT was performed successfully on the first attempt, while in the TracheoQuick Plus group, it was only 18% (P < 0.001). Trauma to the posterior tracheal wall was observed once in the BACT group and 5 times in the TracheoQuick Plus group. Oxygen saturation was significantly higher in the BACT group both during and after the procedure. BACT is superior to TracheoQuick Plus cricothyrotomy on a live animal model.


Fluoride-selective optical sensor based on aluminum(III)-octaethylporphyrin in thin polymeric film: further characterization and practical application.
More detailed analytical studies of a new fluoride-selective optical sensor based on the use of aluminum(III)-octaethylporphyrin and a lipophilic pH indicator (4',5'-dibromofluorescein octadecyl ester; ETH-7075) within a thin plasticized poly(vinyl chloride) film are reported. The sensor exhibits extraordinary optical selectivity for fluoride over a wide range of other anions, including anions with far more positive free energies of hydration (e.g., perchlorate, thiocyanate, nitrate, etc.). UV-visible spectrophotometric studies of the sensing films indicate that fluoride interacts with the Al(III) center of the porphyrin structure, yielding both a change in the Soret band lambda(max) of the porphyrin and a change in the protonation state of the pH indicator within the film. The same change in spectral properties of the metalloporphyrin occurs in the absence of added pH indicator or with added tetraphenylborate derivative anionic sites, but optical responses to fluoride in these cases are shown to be irreversible. The presence of the pH indicator and the simultaneous fluoride/proton coextraction equilibrium chemistry is shown to greatly enhance the reversibility of fluoride binding to the Al(III) porphyrin. Optical response toward fluoride can be observed in the range of 0.1 microM-1.6 mM. Optical selectivity coefficients of <10(-6) for common anions (e.g., sulfate, chloride, nitrate, etc.) and <10(-4) for perchlorate and thiocyanate are obtained. Measurements of fluoride in drinking water via the new optical sensor are shown to correlate well with values obtained for the same samples using a classical LaF3-based fluoride ion-selective electrode method.


Subtle gait and balance impairments occur in idiopathic rapid eye movement sleep behavior disorder.
Although motor abnormalities have been flagged as potentially the most sensitive and specific clinical features for predicting the future progression to Parkinson's disease, little work has been done to characterize gait and balance impairments in idiopathic rapid eye movement sleep behavior disorder (iRBD). The objective of this study was to quantitatively determine any static balance as well as gait impairments across the 5 independent domains of gait in polysomnography-confirmed iRBD patients using normal, fast-paced, and dual-task walking conditions. A total of 38 participants (24 iRBD, 14 healthy controls) completed the following 5 different walking trials across a pressure sensor carpet: (1) normal pace, (2) fast pace, (3) while counting backward from 100 by 1s, (4) while naming as many animals as possible, (5) while subtracting 7s from 100. Although no gait differences were found between the groups during normal walking, there were significant differences between groups under the fast-paced and dual-task gait conditions. Specifically, in response to the dual tasking, healthy controls widened their step width without changing step width variability, whereas iRBD patients did not widen their step width but, rather, significantly increased their step width variability. Similarly, changes between the groups were observed during fast-paced walking wherein the iRBD patients demonstrated greater step length asymmetry when compared with controls. This study demonstrates that iRBD patients have subtle gait impairments, which likely reflect early progressive degeneration in brainstem regions that regulate both REM sleep and gait coordination. Such gait assessments may be useful as a diagnostic preclinical screening tool for future fulminant gait abnormalities for trials of disease-preventive agents. © 2019 International Parkinson and Movement Disorder Society.


Intravascular lymphomatosis (malignant angioendotheliomatosis). A B-cell neoplasm expressing surface homing receptors.
We report the clinical and immunohistochemical features of six cases of intravascular lymphomatosis. All patients presented with symptoms referable to central nervous system (CNS) involvement. In two patients, the diagnosis was made on brain biopsy specimens. In the remaining four cases, diagnosis was made at autopsy. Three of the four autopsied patients had focal extravascular lymphoma, diffuse large cell type. In all five cases tested, immunohistochemical stains on paraffin-embedded sections confirmed the lymphoid nature of the malignant cells. Stains on frozen sections in one case, and on paraffin-embedded tissue in the other four cases, demonstrated B-lymphocyte lineage. In the remaining case, electron microscopy confirmed the lymphoid nature of the tumor cells. All three cases tested expressed the Hermes 3-defined homing receptor antigen and lacked peanut agglutinin receptors. Our results are consistent with other reports confirming the lymphoid nature of so-called malignant angioendotheliomatosis. Our limited analysis of surface receptor molecules suggests that the expression of the homing receptor for high endothelial venules is not in itself responsible for the unusual intravascular location of these cells.


Puzzle of magnetic moments of Ni clusters revisited using quantum Monte Carlo method.
The puzzle of the magnetic moments of small nickel clusters arises from the discrepancy between values predicted using density functional theory (DFT) and experimental measurements. Traditional DFT approaches underestimate the magnetic moments of nickel clusters. Two fundamental problems are associated with this puzzle, namely, calculating the exchange-correlation interaction accurately and determining the global minimum structures of the clusters. Theoretically, the two problems can be solved using quantum Monte Carlo (QMC) calculations and the ab initio random structure searching (AIRSS) method correspondingly. Therefore, we combined the fixed-moment AIRSS and QMC methods to investigate the magnetic properties of Nin (n = 5-9) clusters. The spin moments of the diffusion Monte Carlo (DMC) ground states are higher than those of the Perdew-Burke-Ernzerhof ground states and, in the case of Ni8-9, two new ground-state structures have been discovered using the DMC calculations. The predicted results are closer to the experimental findings, unlike the results predicted in previous standard DFT studies.


Establishment of new murine embryonic stem cell lines for the generation of mouse models of human genetic diseases.
Embryonic stem cells are totipotent cells derived from the inner cell mass of blastocysts. Recently, the development of appropriate culture conditions for the differentiation of these cells into specific cell types has permitted their use as potential therapeutic agents for several diseases. In addition, manipulation of their genome in vitro allows the creation of animal models of human genetic diseases and for the study of gene function in vivo. We report the establishment of new lines of murine embryonic stem cells from preimplantation stage embryos of 129/Sv mice. Most of these cells had a normal karyotype and an XY sex chromosome composition. The pluripotent properties of the cell lines obtained were analyzed on the basis of their alkaline phosphatase activity and their capacity to form complex embryoid bodies with rhythmically contracting cardiomyocytes. Two lines, USP-1 and USP-3, with the best in vitro characteristics of pluripotency were used in chimera-generating experiments. The capacity to contribute to the germ line was demonstrated by the USP-1 cell line. This cell line is currently being used to generate mouse models of human diseases.


Isomerization dynamics and thermodynamics of ionic argon clusters.
The dynamics and thermodynamics of small Ar(n) (+) clusters, n=3, 6, and 9, are investigated using molecular dynamics (MD) and exchange Monte Carlo (MC) simulations. A diatomic-in-molecule Hamiltonian provides an accurate model for the electronic ground state potential energy surface. The microcanonical caloric curves calculated from MD and MC methods are shown to agree with each other, provided that the rigorous conservation of angular momentum is accounted for in the phase space density of the MC simulations. The previously proposed projective partition of the kinetic energy is used to assist MD simulations in interpreting the cluster dynamics in terms of inertial, internal, and external modes. The thermal behavior is correlated with the nature of the charged core in the cluster by computing a dedicated charge localization order parameter. We also perform systematic quenches to establish a connection with the various isomers. We find that the Ar(3) (+) cluster is very stable in its linear ground state geometry up to about 300 K, and then isomerizes to a T-shaped isomer in which a quasineutral atom lies around a charged dimer. In Ar(6) (+) and Ar(9) (+), the covalent trimer core is solvated by neutral atoms, and the weakly bound solvent shell melts at much lower energies, occasionally leading to a tetramer or pentamer core with weakly charged extremities. At high energies the core itself becomes metastable and the cluster transforms into Ar(2) (+) solvated by a fluid of neutral argon atoms.


Detection of single unit spikes during orthodromic-high frequency stimulation in rat hippocampus.
Deep brain stimulation (DBS) has been used as a treatment of brain diseases such as Parkinson's disease and is a promising therapy for epilepsy. But the mechanisms of high frequency stimulation (HFS) used by DBS are still uncertain. In order to investigate the changes of action penitential firings of individual neurons (single unit activity, SUA) during the period of HFS, a new algorithm based on window detection was designed to detect spikes in broadband-frequency recording signals. The results show that orthodromic-HFS (O-HFS) could excite the neurons in CA1 regions, and the firing rate of interneurons and pyramidal neurons increased significantly. In particular, a decrease in spike amplitude for both interneurons and pyramidal neurons was observed during the period of O-HFS. The amplitude decrease of unit spikes was most remarkable with the presence of HFS-induced population spike (PS). These results suggest that the stimulation pulses of O-HFS could activate the downstream neurons continuously, leading to the downstream neurons being unable to repolarize completely. The results are important for tracking individual neuron activity during HFS and for further understanding of DBS mechanisms.


Palliation of pain associated with metastatic bone cancer using samarium-153 lexidronam: a double-blind placebo-controlled clinical trial.
To evaluate the effectiveness and safety of samarium-153 (153Sm) lexidronam (EDTMP) in a double-blind, placebo-controlled study. Patients with painful bone metastases secondary to a variety of primary malignancies were randomized to receive 153Sm-EDTMP 0.5 or 1.0 mCi/kg, or placebo. Treatment was unblinded for patients who did not respond by week 4, with those who had received placebo eligible to receive 1.0 mCi/kg of active drug in an open-label manner. Patient and physician evaluations were used to assess pain relief, as was concurrent change in opioid analgesia. One hundred eighteen patients were enrolled onto the study. Patients who received 1.0 mCi/kg of active drug had significant reductions in pain during each of the first 4 weeks in both patient-rated and physician-rated evaluations. Pain relief was observed in 62% to 72% of those who received the 1.O-mCi/kg dose during the first 4 weeks, with marked or complete relief noted in 31% by week 4. Persistence of pain relief was seen through week 16 in 43% of patients who received 1.0 mCi/kg, of active drug. A significant correlation (P = .01) was observed between reductions in opioid analgesic use and pain scores only for those patients who received 1.0 mCi/kg 153Sm-EDTMP. Bone marrow suppression was mild, reversible, and not associated with grade 4 toxicity. A single dose of 1.0 mCi/kg of 153Sm-EDTMP provided relief from pain associated with bone metastases. Pain relief was observed within 1 week of administration and persisted until at least week 16 in the majority of patients who responded.


Salmon subsidies predict territory size and habitat selection of an avian insectivore.
The annual migration and spawning event of Pacific salmon (Oncorhynchus spp.) can lead to cross-boundary delivery of marine-derived nutrients from their carcasses into adjacent terrestrial ecosystems. The densities of some passerine species, including Pacific wrens (Troglodytes pacificus), have been shown to be positively correlated with salmon abundance along streams in Alaska and British Columbia, but mechanisms maintaining these densities remain poorly understood. Riparian areas near salmon streams could provide higher quality habitat for birds through greater food availability and more suitable vegetation structure for foraging and breeding, resulting in wrens maintaining smaller territories. We examined relationships between salmon biomass and Pacific wren territory size, competition, and habitat selection along 11 streams on the coast of British Columbia, Canada. We show that male wren densities increase and territory sizes decrease as salmon-spawning biomass increases. Higher densities result in higher rates of competition as male wrens countersing more frequently to defend their territories along streams with more salmon. Wrens were also more selective of the habitats they defended along streams with higher salmon biomass; they were 68% less likely to select low-quality habitat on streams with salmon compared with 46% less likely at streams without salmon. This suggests a potential trade-off between available high-quality habitat and the cost of competition that structures habitat selection. Thus, the marine-nutrient subsidies provided by salmon carcasses to forests lead to higher densities of wrens while shifting the economics of territorial defence toward smaller territories being defended more vigorously in higher quality habitats.


Acute respiratory distress syndrome, the critical care paradigm: what we learned and what we forgot.
In the last several years, we definitely learned that the acute respiratory distress syndrome lung is small, nonhomogeneous, and that mechanical ventilation in this baby lung may cause physical damage as well as inflammatory reaction. The clinical benefit of the gentle lung treatment, based on a decrease of global/regional stress and strain into the lung, has been finally proved. However, we forgot the importance of lung perfusion and its distribution in this syndrome and, besides a low tidal volume, we still do not know how to handle the other variables of mechanical ventilation. Measurements of variables as transpulmonary pressure and end expiratory lung volume, for a rational setting of mechanical ventilation, should be introduced in routine clinical practice.


Dopamine depletion does not protect against acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine toxicity in vivo.
Dopamine (DA) has been postulated to play a role in the loss of dopaminergic substantia nigra (SN) neurons in Parkinson's disease because of its propensity to oxidize and form quinones and other reactive oxygen species that can alter cellular function. Moreover, DA depletion can attenuate dopaminergic cell loss in vitro. To test the contribution of DA to SN impairment in vivo, we used DA-deficient mice, which lack the enzyme tyrosine hydroxylase in dopaminergic cells, and mice pharmacologically depleted of DA by alpha-methyl-p-tyrosine pretreatment. Mice were treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a toxin that produces parkinsonian pathology in humans, nonhuman primates, and rodents. In contrast to in vitro results, genetic or pharmacologic DA depletion did not attenuate loss of dopaminergic neurons in the SN or dopaminergic neuron terminals in the striatum. These results suggest that DA does not contribute to acute MPTP toxicity in vivo.


A complex social-ecological disaster: Environmentally induced forced migration.
In the 21st century, global issues are increasingly characterized by inter-connectedness and complexity. Global environmental change, and climate change in particular, has become a powerful driver and catalyst of forced migration and internal displacement of people. Environmental migrants may far outnumber any other group of displaced people and refugees in the years to come. Deeper scientific integration, especially across the social sciences, is a prerequisite to tackle this issue.


Specific inhibition of ATP-ADP translocase in cardiac mitoplasts by antibodies against mitochondrial creatine kinase.
Mitochondrial creatine kinase was purified from rat hearts and used to produce antibodies in chicken and rabbits. Antibodies were purified to a high degree of homogeneity by an affinity chromatography method. Chicken antibodies against mitochondrial creatine kinase inhibited this enzyme in rat-heart mitochondrial inner membrane and matrix preparation, and simultaneously blocked oxidative phosphorylation. Under these conditions respiratory chain activities remained unchanged, but adenine nucleotide translocase was inhibited. Removal of mitochondrial creatine kinase from the membrane by pretreatment with 0.15 M KCl and 20 mM ADP completely abolished the effect of antibodies against mitochondrial creatine kinase on oxidative phosphorylation. Noninhibitory antibodies from rabbit with high affinity to rat mitochondrial creatine kinase inhibited neither creatine kinase activity nor oxidative phosphorylation. These data show close and specific spatial arrangement of mitochondrial creatine kinase and adenine nucleotide translocase in mitochondria. It is supposed that there is a fixed orientation of these proteins in the cardiolipin domain in the membrane and that their interaction may occur by a frequent collision due to their lateral movement.


Pathologic Surface Changes in the Submental Flap Used for Intraoral Reconstruction: Report of Two Cases.
Soft tissue reconstruction is often necessary after pathologic resection of oral squamous cell carcinoma. Although morphologic changes are common after transfer of the flaps to the oral cavity, pathologic changes within the transferred flaps, used for intraoral reconstruction, are rare events. Despite the widespread use of submental flap for oral cavity reconstruction, there are no reports in this respect. In this article, pathologic changes in the surface epithelium of transferred submental flaps are demonstrated with the report of two cases. The occurrence of lichen planus in a submental flap that had been used for reconstruction of lateral tongue border is reported in one case and in another patient, squamous cell carcinoma arising in the transferred de-epithelialized submental flap, used for maxillary and buccal reconstruction, is shown.


Oropharyngeal cancer prognosis by tumour HPV status in France: The multicentric Papillophar study.
To evaluate the impact of human papillomavirus (HPV) status, tobacco smoking and initial treatment approach on progression-free survival (PFS) and overall survival (OS) for oropharyngeal cancer (OPC) in France, a country where smoking declines started late (1990s). 340 OPC patients (median age: 60years) from 14 French hospitals were followed up (median 26.7months). PCR-based positivity for both HPV DNA and E6/E7 mRNA was used to distinguish HPV-positive OPC (27.1%). Hospital-stratified hazard ratios (HR) and corresponding 95% confidence intervals (CI) were used to compare PFS and OS according to HPV and other prognostic factors in hospital-stratified unadjusted and multivariate models. The combined effect of HPV status with either smoking, stage, or initial treatment on PFS was also evaluated. PFS in multivariate analysis was better in HPV-positive patients (HR=0.42; 95% CI: 0.24-0.73) and worse in older patients (HR for 5-year age increase=1.12) and those having had firstly radiotherapy (HR=1.86; 95% CI: 1.19-2.92) or induction chemotherapy (HR=1.73; 95% CI: 1.08-2.79) instead of upfront surgery. Findings for OS were similar. Loco-regional recurrences were less frequent in HPV-positive (10.5%) than HPV-negative patients (26.0%) but distant recurrences were similarly frequent. HPV status did not modify the influence of smoking or stage on PFS but the impossibility to perform upfront surgery may be more relevant for HPV-negative patients. HPV-positive OPC patients fare better than HPV-negative OPC and may benefit from toxicity-sparing. Whether HPV-negative patients responded less well to radiation and chemotherapy because of more severe genomic damage or bulkier tumours is unclear.


Fall risk in the elderly.
Falls contribute to significant morbidity and mortality in the elderly. This article identifies a number of intrinsic and extrinsic factors that increase the risk for falling. Application of effective clinical strategies that have been identified through research to reduce the occurrence of falls is a necessary component of caring for the elderly. As this population increases, so must nurses' knowledge of implementing successful fall prevention programs.


Laser scanning microscopy study on adsorption of biologically relevant proteins on implant materials.
The adsorption of proteins at implant surfaces plays a key role in osseointegration and is therefore of great importance in biomaterial science. Laser scanning microscopy (LSM) is described, a method that is used here for the first study of the adsorption of proteins on implant surfaces. These LSM measurements provide information on the surface morphology, and the spatial distribution of adsorbed proteins can be deduced.


[Management of Type 2 Diabetes: a Practical Approach].
Over the last years, the therapeutic aims for patients with type 2 diabetes have changed and several novel drugs have been introduced. In this Mini-Review we discuss these aims and how to achieve them.


The percentage of patients achieving PASI 75 after 1 month and remission time after climatotherapy at the Dead Sea.
Dead Sea climatotherapy (DSC) is a highly effective treatment for psoriasis; however, there are scanty data concerning the duration of post-therapy remission. Assessment of the duration of remission in patients suffering from plaque-type psoriasis after a 4-week DSC. Sixty-four patients from Germany (66% men; average age: 41.5 years) underwent a 4-week course of DSC between September 2001 and November 2002. After returning home, patients were asked to inform their dermatologist immediately when new lesions appeared. In parallel, they were called every 3 months by telephone. All patients who reported new skin lesions underwent a physical examination, including a Psoriasis Assessment Severity Index (PASI). (1) Time of recurrence of a psoriatic lesion after complete or almost complete clearance, defined as duration of remission; (2) time that elapsed until a relapse of 50% of the PASI improvement occurred, defined as duration of therapeutic effect. Mean PASI value before and after treatment was 31.7 and 1.42, showing a 95.5% improvement. All patients reached PASI 50, and 75.9% of them reached PASI 75 after 1 month of DSC. The median time of remission was 23.1 weeks. The median time of duration of therapeutic effect was 33.6 weeks. Statistical multivariable analysis indicated that a patient's younger age at the time of treatment was associated with a longer period of remission. Four-week DSC is an effective remittive treatment for plaque-type psoriasis. The period of remission induced compares favorably with other accepted modalities of treatment.


Identification of the Anabaena sp. strain PCC7120 cyanophycin synthetase as suitable enzyme for production of cyanophycin in gram-negative bacteria like Pseudomonas putida and Ralstonia eutropha.
The cyanophycin synthetase gene cphA1 encoding the major cyanophycin synthetase (CphA) of Anabaena sp. strain PCC7120 was expressed in Escherichia coli conferring so far the highest specific CphA activity to E. coli (6.7 nmol arginine per min and mg protein). CphA1 and cphA genes of Synechocystis sp. strains PCC6803 and PCC6308 and Synechococcus strain MA19 were also expressed in wild types and polyhydroxyalkanoate-negative (PHA) mutants of Pseudomonas putida and Ralstonia eutropha. Recombinant strains of these bacteria expressing cphA1 accumulated generally more cyanophycin (23.0 and 20.0% of cellular dry matter, CDM, respectively) than recombinants expressing any other cphA (6.8, 9.0, or 15.8% of CDM for P. putida strains and 7.3, 12.6, or 14.1% of CDM for R. eutropha). Furthermore, PHA-negative mutants of P. putida (9.7, 10.0, 17.5, or 24.0% of CDM) and R. eutropha (8.9, 13.8, 16.0, or 22.0% of CDM) accumulated generally more cyanophycin than the corresponding PHA-positive parent strains (6.8, 9.0, 15.8, and 23.0% of CDM for P. putida strains and 7.3, 12.6, 14.1, or 20.0% of CDM for R. eutropha strains). Recombinant strains of Gram-positive bacteria (Bacillus megaterium, Corynebacterium glutamicum) were not suitable for cyanophycin production due to accumulation of less cyanophycin and retarded release of cyanophycin. PHA-negative mutants of P. putida and R. eutropha expressing cphA1 of Anabaena sp. strain PCC7120 are therefore preferred candidates for industrial production of cyanophycin.


Children's Sympathy, Guilt, and Moral Reasoning in Helping, Cooperation, and Sharing: A 6-Year Longitudinal Study.
This study examined the role of sympathy, guilt, and moral reasoning in helping, cooperation, and sharing in a 6-year, three-wave longitudinal study involving 175 children (Mage 6.10, 9.18, and 12.18 years). Primary caregivers reported on children's helping and cooperation; sharing was assessed behaviorally. Child sympathy was assessed by self- and teacher reports, and self-attributed feelings of guilt-sadness and moral reasoning were assessed by children's responses to transgression vignettes. Sympathy predicted helping, cooperation, and sharing. Guilt-sadness and moral reasoning interacted with sympathy in predicting helping and cooperation; both sympathy and guilt-sadness were associated with the development of sharing. The findings are discussed in relation to the emergence of differential motivational pathways to helping, cooperation, and sharing.


Hemodiafiltration Decreases Serum Levels of Inflammatory Mediators in Severe Leptospirosis: A Prospective Study.
Leptospirosis is a health problem worldwide. Its most severe form is a classic model of sepsis, provoking acute respiratory distress syndrome (ARDS) and acute kidney injury (AKI), with associated mortality that remains unacceptably high. We previously demonstrated that early initiation of sustained low-efficiency dialysis (SLED) followed by daily SLED significantly decreases mortality. However, the mode of clearance can also affect dialysis patient outcomes. Therefore, the objective of this study was to compare the effects of SLED with traditional (diffusive) clearance, via hemodialysis, and SLED with convective clearance, via hemodiafiltration (SLEDf), in patients with severe leptospirosis. In this prospective study, conducted in the intensive care unit (ICU) from 2009 through 2012, we compared two groups-SLED (n = 19) and SLEDf (n = 20)-evaluating demographic, clinical, and biochemical parameters, as well as serum levels of interleukins, up to the third day after admission. All patients received dialysis early and daily thereafter. During the study period, 138 patients were admitted to our ICU with a diagnosis of leptospirosis; 39 (36 males/3 females) met the criteria for ARDS and AKI. All patients were on mechanical ventilation and were comparable in terms of respiratory parameters. Mortality did not differ between the SLEDf and SLED groups. However, post-admission decreases in the serum levels of interleukin (IL)-17, IL-7, and monocyte chemoattractant protein-1 were significantly greater in the SLEDf group. Direct bilirubin and the arterial oxygen tension/fraction of inspired oxygen ratio were significantly higher in the SLED group. We identified the following risk factors (sensitivities/specificities) for mortality in severe leptospirosis: age ≥ 55 years (67%/91%); serum urea ≥ 204 mg/dl (100%/70%); creatinine ≥ 5.2 mg/dl (100%/58%); Acute Physiology and Chronic Health Evaluation II score ≥ 39.5 (67%/88%); Sequential Organ Failure Assessment score ≥ 20.5 (67%/85%); and inspiratory pressure ≥ 31 mmHg (84%/85%). The mode of dialysis clearance might not affect outcomes in severe leptospirosis.


A case of angiosarcoma of the breast.
This is a case report of a 20-year-old woman who had primary angiosarcoma of the left breast, with metastases to the spleen and ovary. Eight months after detecting a mass in her breast, she underwent mastectomy with biopsy of the ipsilateral axillary lymph nodes, splenectomy and bilateral oophorectomy. Five months after the operation, the patient succumbed to lung metastases. Angiosarcoma of the breast is a rare condition with a poor prognosis, and there are no established chemotherapeutic regimens as yet. Immunohistochemical staining for endoglin, known to be expressed mainly on the surface of endothelial cells, was positive. This suggests the possibility of treating angiosarcoma with anti-endoglin monoclonal antibodies.


[Angiomatous choroidal and orbital lesions in a patient with Sturge Weber syndrome].
We present the case of a 34-year-old man with Sturge-Weber syndrome, who presented to the emergency room with left ocular pain and left chronic exophthalmos. He suffered an acute glaucoma secondary to pupillary block consequent upon an anterior lens subluxation. Orbital contrast Magnetic Resonance Imaging (MRI) was performed and he underwent intracapsular lens extraction. The MRI showed T2 enhanced lesions in the left meninges, choroid, and orbit, compatible with cavernous hemangiomas, as well as a dilated superior ophthalmic vein. Intraocular pressure after cataract surgery was 10 mm Hg, and visual acuity was less than 20/200.


Cyclic AMP regulates transcription of the genes encoding human chorionic gonadotropin with different kinetics.
Choriocarcinoma cell lines characteristically synthesize and secrete the alpha- and beta-subunits of human chorionic gonadotropin (hCG), as well as the intact heterodimer. Treatment of one such cell line, BeWo, with 8-bromo-adenosine 3':5'-cyclic monophosphate (8-Br-cAMP) causes at least a 10-fold increase in the concentration of the mRNA encoding each subunit. Changes in mRNA concentrations are associated with similar changes in transcription rates of both the CG alpha and CG beta genes, although the kinetics of their transcriptional responses are different. Transcription of the alpha-subunit gene increases rapidly and becomes maximal within 1 hr after addition of 8-Br-cAMP. By contrast, transcription of the CG beta gene increases slowly and progressively for at least 8 hr after treatment with 8-Br-cAMP. The slow transcriptional response of the CG beta gene(s) appears to be unique compared to that of other cAMP-responsive genes, and suggests that the cyclic nucleotide may regulate transcription of the CG genes by different mechanisms.


Reconstruction of a Subtotal Maxillectomy Defect Using a Customized Titanium Implant in a 4-Year-Old Child: An 8-Year Follow-Up Report.
Condition: This case report demonstrates the use of alloplastic reconstruction in young children. Method: A three-dimensionally printed titanium implant was used to reconstruct a subtotal maxillectomy defect in a 4-year-old child. Results: We report an 8-year follow-up. The endoprosthesis was split at the midline to address transverse growth. The main finding is that the stigma surrounding resection and surgical reconstruction in pre-adolescents can be prevented by the use of alloplastic reconstruction based on titanium osseointegration. An additional finding is that shear forces should be prevented at the insertion points of the fixation screws in the facial walls by providing a vertical support for the maxillary/palatal shelves. Lastly, transverse maxillary growth in the circumferential sutures and functional matrix was not hampered by splitting the endo- and exoprostheses in the middle (where the mid-palatal suture would normally be located). Conclusion: Alloplastic reconstruction of maxillectomy defects in childhood can offer a viable temporary solution.


Use of the six core surgical indicators from the Lancet Commission on Global Surgery in Colombia: a situational analysis.
Surgical, anaesthetic, and obstetric (SAO) health-care system strengthening is needed to address the emergency and essential surgical care that approximately 5 billion individuals lack globally. To our knowledge, a complete, non-modelled national situational analysis based on the Lancet Commission on Global Surgery surgical indicators has not been done. We aimed to undertake a complete situation analysis of SAO system preparedness, service delivery, and financial risk protection using the core surgical indicators proposed by the Commission in Colombia, an upper-middle-income country. Data to inform the six core surgical system indicators were abstracted from the Colombian national health information system and the most recent national health survey done in 2007. Geographical access to a Bellwether hospital (defined as a hospital capable of providing essential and emergency surgery) within 2 h was assessed by determining 2 h drive time boundaries around Bellwether facilities and the population within and outside these boundaries. Physical 2 h access to a Bellwether was determined by the presence of a motor vehicle suitable for individual transportation. The Department Administrativo Nacional de Estadística population projection for 2016 and 2018 was used to calculate the SAO provider density. Total operative volume was calculated for 2016 and expressed nationally per 100 000 population. The total number of postoperative deaths that occurred within 30 days of a procedure was divided by the total operative volume to calculate the all-cause, non-risk-adjusted postoperative mortality. The proportion of the population subject to impoverishing costs was calculated by subtracting the baseline number of impoverished individuals from those who fell below the poverty line once out-of-pocket payments were accounted for. Individuals who incurred out-of-pocket payments that were more than 10% of their annual household income were considered to have experienced catastrophic expenditure. Using GIS mapping, SAO system preparedness, service delivery, and cost protection were also contextualised by socioeconomic status. In 2016, at least 7·1 million people (15·1% of the population) in Colombia did not have geographical access to SAO services within a 2 h driving distance. SAO provider density falls short of the Commission's minimum target of 20 providers per 100 000 population, at an estimated density of 13·7 essential SAO health-care providers per 100 000 population in 2018. Lower socioeconomic status of a municipality, as indicated by proportion of people enrolled in the subsidised insurance regime, was associated with a smaller proportion of the population in the municipality being within 2 h of a Bellwether facility, and the most socioeconomically disadvantaged municipalities often had no SAO providers. Furthermore, Colombian providers appear to be working at or beyond capacity, doing 2690-3090 procedures per 100 000 population annually, but they have maintained a relatively low median postoperative mortality of 0·74% (IQR 0·48-0·84). Finally, out-of-pocket expenses for indirect health-care costs were a key barrier to accessing surgical care, prompting 3·1 million (6·4% of the population) individuals to become impoverished and 9·5 million (19·4% of the population) individuals to incur catastrophic expenditures in 2007. We did a non-modelled, indicator-based situation analysis of the Colombian SAO system, finding that it has not yet met, but is working towards achieving, the targets set by the Lancet Commission on Global Surgery. The observed interdependence of these indicators and correlation with socioeconomic status are consistent with well recognised factors and outcomes of social, health, and health-care inequity. The internal consistency observed in Colombia's situation analysis validates the use of the indicators and has now informed development of an early national SAO plan in Colombia, to set a data-informed stage for implementation and evaluation of timely, safe, and affordable SAO health care, within the National Public Health Decennial Plan, which is due in 2022. Zoll Medical.


Clinical Course and Outcome of Prenatally Detected 22q11.2 Deletion Syndrome-A Retrospective Analysis.
The 22q11.2 deletion syndrome (22q11.2 DS) is known as the most common microdeletion syndrome. Due to its variable clinical phenotype, prenatal diagnosis can be challenging. The aim of this retrospective study was to evaluate the clinical course and pregnancy outcome of cases with prenatally diagnosed 22q11.2 deletion syndrome (DS) as well as to evaluate the role of prenatal magnetic resonance imaging (MRI) and postmortem examination. In total, 21 cases who underwent prenatal ultrasound examination and pregnancy care at the Department of Obstetrics and Gynecology at the Medical University of Vienna between 2012 and 2022 were included. The majority of the cases were genetically diagnosed using fluorescent in situ hybridization (FISH). The median gestational age (GA) at genetic diagnosis was 23.0 weeks (IQR 21.4-24.8 weeks). CHDs were detected in all fetuses and the most common extracardiac manifestation was thymus hypo/aplasia followed by genitourinary anomalies. Prenatal magnetic resonance imaging (MRI) revealed additional diagnostic information in three of ten cases. Overall, 14 patients opted for drug-induced TOP, of which 9 cases had a feticide prior to the induction of labor. The majority of craniofacial malformations were only detected by autopsy. In conclusion, the majority of cases prenatally diagnosed with 22q11.2 DS had an absent or hypoplastic thymus noted antenatally in addition to the detected CHD, and almost half of the cases had another extracardiac malformation of predominantly genitourinary origin. Furthermore, prenatal MRIs confirmed previously detected malformations, but only provided additional diagnostic information in three out of ten cases, whereas postmortem examination diagnosed most of the craniofacial anomalies and should always be conducted, serving as an important quality indicator for prenatal imaging.


What criteria do decision makers in Thailand use to set priorities for vaccine introduction?
There is a need to identify rational criteria and set priorities for vaccines. In Thailand, many licensed vaccines are being considering for introduction into the Expanded Program on Immunization; thus, the government has to make decisions about which vaccines should be adopted. This study aimed to set priorities for new vaccines and to facilitate decision analysis. We used a best-worst scaling study for rank-ordering of vaccines. The candidate vaccines were determined by a set of criteria, including burden of disease, target age group, budget impact, side effect, effectiveness, severity of disease, and cost of vaccine. The criteria were identified from a literature review and by in-depth, open-ended interviews with experts. The priority-setting model was conducted among three groups of stakeholders, including policy makers, healthcare professionals and healthcare administrators. The vaccine data were mapped and then calculated for the probability of selection. From the candidate vaccines, the probability of hepatitis B vaccine being selected by all respondents (96.67 %) was ranked first. This was followed, respectively, by pneumococcal conjugate vaccine-13 (95.09 %) and Haemophilus influenzae type b vaccine (90.87 %). The three groups of stakeholders (policy makers, healthcare professionals and healthcare administrators) showed the same ranking trends. Most severe disease, high fever rate and high disease burden showed the highest coefficients for criterion levels being selected by all respondents. This result can be implied that a vaccine which can prevent most severe disease with high disease burden and has low safety has a greater chance of being selected by respondents in this study. The priority setting of vaccines through a multiple-criteria approach could contribute to transparency and accountability in the decision-making process. This is a step forward in the development of an evidence-based approach that meets the need of developing country. The methodology is generalizable but its application to another country would require the criteria as relevant to that country.


Cybersecurity Awareness Based on Software and E-mail Security with Statistical Analysis.
The aim of this study is to discover the impact of software security and e-mail security on overall cybersecurity among the students of Imam Abdulrahman Bin Faisal University in Dammam. Another main purpose to conduct this study is to know the level of knowledge students have in the developing countries about the cybersecurity and how much are they mindful of cyber-attacks and the level of awareness among the university students. Two important hypotheses were studied to discover their importance in awareness of cybersecurity. One is software security, and the other is e-mail security. A total of 11 relevant questions were drafted, and then these questions were distributed among the university students, and around 390 responded to the questionnaires. Statistical analysis was performed on the responses using tools. Initial tests such as validity and reliability test, feasibility test of a variable, correlation test, multicollinearity test, multiple regression, and Heteroskedasticity test were conducted using SPSS. And furthermore, multiple linear regression model and coefficient of determination, hypothesis test, ANOVA test, and partial test were conducted using ANOVA. The outcome of the analysis is software security variable (X1) that has a significant and positive effect on cybersecurity awareness (p value ≤0.001, β = 0.192). This shows that having a thorough understanding of software security can raise cybersecurity awareness up to 19.2%. E-mail security variable (X2) has a significant and positive effect on cybersecurityawareness (p-value ≤0.000). This shows that having a thorough understanding of email security can raise cybersecurity awareness up to 31.3%. Software security (X1) and e-mail security (X2) variables simultaneously have a significant effect on cybersecurity awareness (p-value ≤0.000) with a correlation coefficient of 12.1% (R2 = 0.121). This shows that the independent variable used can explain the level of cybersecurity awareness up to 12.1%. Research results show that students are aware of software or application updates. Furthermore, students' awareness of email security is also good.


Three new nor-dammarane triterpenoids from Dysoxylum hainanense with particular cytotoxicity against glioma cell line.
Three new nor-dammarane triterpenoids, 12β-O-acetyl-15α-hydoxy-3-oxo-17-en-20,21,22-23,24,25,26,27-octanordammanran (1), 12β,28-O-diacetyl-15α-hydoxy-3-oxo-17-en-20,21,22-23,24,25,26,27-octanordammanran (2), 12β-hydoxy-3,15-dioxo-20,21,22-23,24,25,26,27-octanordammanran (3), together with one known compound, 12β-O-acetyl-15α,28-dihydoxy-3-oxo-17-en-20,21,22-23,24,25,26,27-octanordammanran (4), were isolated from the 95 % EtOH extract of Dysoxylum hainanense. The structures of the new compounds were elucidated by spectral methods. All the triterpenoids were in vitro evaluated for their cytotoxic activities against four tumor cell lines (BGC-823, U251, HepG2 and SGC-7901). All the three nor-dammarane triterpenoids exhibited particular significant cytotoxic activities against glioma cell line.