Generation of robust left-right asymmetry in the mouse embryo requires a self-enhancement and lateral-inhibition system.
The bilateral symmetry of the mouse embryo is broken by leftward fluid flow in the node. However, it is unclear how this directional flow is then translated into the robust, left side-specific Nodal gene expression that determines and coordinates left-right situs throughout the embryo. While manipulating Nodal and Lefty gene expression, we have observed phenomena that are indicative of the involvement of a self-enhancement and lateral-inhibition (SELI) system. We constructed a mathematical SELI model that not only simulates, but also predicts, experimental data. As predicted by the model, Nodal expression initiates even on the right side. These results indicate that directional flow represents an initial small difference between the left and right sides of the embryo, but is insufficient to determine embryonic situs. Nodal and Lefty are deployed as a SELI system required to amplify this initial bias and convert it into robust asymmetry.


Early outcome of hip arthroscopy for femoroacetabular impingement: the role of femoral osteoplasty in symptomatic improvement.
There is a known association between femoroacetabular impingement and osteoarthritis of the hip. What is not known is whether arthroscopic excision of an impingement lesion can significantly improve a patient's symptoms. This study compares the results of hip arthroscopy for cam-type femoracetabular impingement in two groups of patients at one year. The study group comprised 24 patients (24 hips) with cam-type femoroacetabular impingement who underwent arthroscopic debridement with excision of their impingement lesion (osteoplasty). The control group comprised 47 patients (47 hips) who had arthroscopic debridement without excision of the impingement lesion. In both groups, the presence of femoroacetabular impingement was confirmed on pre-operative plain radiographs. The modified Harris hip score was used for evaluation pre-operatively and at one-year. Non-parametric tests were used for statistical analysis. A tendency towards a higher median post-operative modified Harris hip score was observed in the study group compared with the control group (83 vs 77, p = 0.11). There was a significantly higher proportion of patients in the osteoplasty group with excellent/good results compared with the controls (83% vs 60%, p = 0.043). Additional symptomatic improvement may be obtained after hip arthroscopy for femoroacetabular impingement by the inclusion of femoral osteoplasty.


Operation management system evaluation in the central Finland health care district - end users' view of system implementation.
In this paper we evaluate the implementation of the operation management system in the Central Finland Health Care District. The implementation of the operation management system changed the practice of operation management for the surgical clinic and concerned 500 personnel in total. A survey was carried out to investigate the end users' views on the system's usefulness, usability and the training and user support provided. The users' possibilities to accomplish their tasks and the kind of obstacles they face in operation management were explored. The assessment revealed that more end support is needed after the system implementation, even though a generally positive attitude towards the system was manifested among the staff.


Adolescence in lockdown: The protective role of mentalizing and epistemic trust.
Mentalizing is the ability to interpret one's own and others' behavior as driven by intentional mental states. Epistemic trust (openness to interpersonally transmitted information) has been associated with mentalizing. Balanced mentalizing abilities allow people to cope with external and internal stressors. Studies show that social isolation imposed by the COVID-19 pandemic was highly stressful for most people, especially for adolescents. Here we examine whether mentalizing and epistemic trust were protective factors in relation to emotional distress during the lockdown. A total of 131 nonclinical adolescents, aged between 12 and 18 years, were evaluated during the lockdown using the Reflective Functioning Questionnaire for Youth, Inventory of Parent and Peer Attachment, Perceived Stress Scale, and Difficulties in Emotion Regulation Scale. Results from network analysis showed that epistemic trust and mentalizing were negatively associated with perceived stress and emotion dysregulation. Epistemic trust in fathers was associated with level of perceived stress, and epistemic trust in mothers with emotion dysregulation. These findings suggest that epistemic trust and the capacity to mentalize were low in adolescents during lockdown, and this was associated with high levels of stress. However, robust levels of epistemic trust and mentalizing may have acted as protective factors that buffered individuals from the risk of emotional dysregulation during the lockdown.


Using the concept of transient complex for affinity predictions in CAPRI rounds 20-27 and beyond.
Predictions of protein-protein binders and binding affinities have traditionally focused on features pertaining to the native complexes. In developing a computational method for predicting protein-protein association rate constants, we introduced the concept of transient complex after mapping the interaction energy surface. The transient complex is located at the outer boundary of the bound-state energy well, having near-native separation and relative orientation between the subunits but not yet formed most of the short-range native interactions. We found that the width of the binding funnel and the electrostatic interaction energy of the transient complex are among the features predictive of binders and binding affinities. These ideas were very promising for the five affinity-related targets (T43-45, 55, and 56) of CAPRI rounds 20-27. For T43, we ranked the single crystallographic complex as number 1 and were one of only two groups that clearly identified that complex as a true binder; for T44, we ranked the only design with measurable binding affinity as number 4. For the nine docking targets, continuing on our success in previous CAPRI rounds, we produced 10 medium-quality models for T47 and acceptable models for T48 and T49. We conclude that the interaction energy landscape and the transient complex in particular will complement existing features in leading to better prediction of binding affinities.


Medical Research Volunteer Program (MRVP): innovative program promoting undergraduate research in the medical field.
Most educational institutions lack a structured system that provides undergraduate students with research exposure in the medical field. The objective of this paper is to describe the structure of the Medical Research Volunteer Program (MRVP) which was established at the American University of Beirut, Lebanon, as well as to assess the success of the program. The MRVP is a program that targets undergraduate students interested in becoming involved in the medical research field early on in their academic career. It provides students with an active experience and the opportunity to learn from and support physicians, clinical researchers, basic science researchers and other health professionals. Through this program, students are assigned to researchers and become part of a research team where they observe and aid on a volunteer basis. This paper presents the MRVP's four major pillars: the students, the faculty members, the MRVP committee, and the online portal. Moreover, details of the MRVP process are provided. The success of the program was assessed by carrying out analyses using information gathered from the MRVP participants (both students and faculty). Satisfaction with the program was assessed using a set of questions rated on a Likert scale, ranging from 1 (lowest satisfaction) to 5 (highest satisfaction). A total of 211 students applied to the program with a total of 164 matches being completed. Since the beginning of the program, three students have each co-authored a publication in peer-reviewed journals with their respective faculty members. The majority of the students rated the program positively. Of the total number of students who completed the program period, 35.1 % rated the effectiveness of the program with a 5, 54.8 % rated 4, and 8.6 % rated 3. A small number of students gave lower ratings of 2 and 1 (1.1 % and 0.4 %, respectively). The MRVP is a program that provides undergraduate students with the opportunity to learn about research firsthand as they volunteer and aid in different research projects. This program also provides faculty members with the help to conduct their research projects and opportunity to influence future generations. It was shown that so far the MRVP has been successful in reaching its goals, for both students and faculty.


Evaluation of the Cytotoxic Activity of Crocin and Safranal, Constituents of Saffron, in Oral Squamous Cell Carcinoma (KB Cell Line).
Crocin and safranal are active ingredients in the saffron. Some studies have demonstrated antitumor activities of saffron ingredients. The aim of this study was to evaluate cytotoxic effects of crocin and safranal in oral squamous cell carcinoma (KB cells) and NIH 3T3 cell line as nonmalignant cells. The cells were incubated with crocin and safranal at 37°C for 24, 48, and 72 h, and cell viability was quantitated by MTT assay. Apoptotic cells, cell cycle distribution, and sub-G1 fraction were determined using propidium iodide staining of DNA fragmentation by flow cytometry. Crocin (0.05-4 mM) and safranal (0.2-3.2 mM) significantly inhibited the growth of KB cells (the inhibitory growth effects of all concentrations for both were >50% after 72 h), while they had less inhibitory effects on NIH 3T3 cells viability. The IC50 values of crocin and safranal against NIH 3T3 cells after 72 h were determined as 2.8 and 0.3 mM, respectively. Crocin and safranal induced a sub-G1 peak in the flow cytometry histogram of treated cells compared to control cells indicating that apoptotic cell death is involved in the toxicity of crocin and safranal. Apoptotic effects of crocin and safranal in tumor cells were more than normal cells. Neither crocin nor safranal affected the cell cycle progression. Crocin and safranal exerted apoptotic effects in KB cell line.


Rapid citrate-agar electrophoresis in routine screening for hemoglobinopathies using a simple hemolysate.
A system for rapid hemoglobin electrophoresis on both cellulose acetate and citrate-agar combined with a simple solubility test for sickling variants is described. By use of a saponin hemolysate of once-washed erythrocytes, all three tests can be performed at one time so that an accurate result of the hemoglobin phenotype can be provided expeditiously. A technic for rapid hemoglobin electrophoresis on citrate-agar, using standard equipment is described in detail.


Incidence of Sinusoidal Obstruction Syndrome/Veno-Occlusive Disease and Treatment with Defibrotide in Allogeneic Transplantation: A Multicenter Australasian Registry Study.
Sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) is an established complication in patients undergoing allogeneic hemopoietic stem cell transplantation (HSCT). Defibrotide is an effective and safe pharmacologic option for treating diagnosed SOS/VOD. By exploring data provided to the Australasian Bone Marrow Transplant Recipient Registry (ABMTRR) by centers in Australia and New Zealand, this study aimed to describe the incidence of SOS/VOD and patterns of defibrotide use from 2016 to 2020. Patients who underwent allogeneic hemopoietic stem cell transplantation between 2016 and 2020 were identified from the ABMTRR. Data were extracted for a total of 3346 patients, 2692 from adult centers and 654 from pediatric centers, with a median follow-up of 21.5 months and 33.3 months, respectively. Descriptive statistics were used to describe the patient population, including the incidence of SOS/VOD and defibrotide use. Comparisons were made between patients without SOS/VOD and those with SOS/VOD, divided into defibrotide and no defibrotide cohorts. Associations with overall survival (OS) and day 100 survival with such variables as sex, age, disease at transplantation, stem cell source, conditioning agents, SOS/VOD diagnosis, and use of defibrotide, were determined. The reported incidence of SOS/VOD was 4.1% in adult centers and 11.5% in pediatric centers. Defibrotide was administered to 74.8% of adult patients and 97.3% of pediatric patients with SOS/VOD. Significant variability in the use, dosage, and duration of defibrotide was seen across the adult centers. The day 100 survival rate and median OS for patients managed with defibrotide was 51.8% and 103 days, respectively, for adult patients and 90.4% and not reached, respectively, for pediatric patients. In adults, older age at transplantation, an HLA-matched nonsibling relative donor, and a diagnosis of SOS/VOD treated with defibrotide were associated with reduced OS. In pediatric patients, the patient and transplantation characteristics associated with reduced OS were a diagnosis of SOS/VOD and a ≥2 HLA-mismatched related donor. A collaborative approach across Australasia to diagnosing and managing SOS/VOD, particularly with respect to consistent defibrotide use, is recommended.


Reproduction, Life-course and Vital Conjunctures in the Context of Austerity.
Reproduction is a considerable concern in contemporary Europe and has attracted growing academic interest in the context of austerity. This paper brings together literature on social reproduction, the life-course and vital conjunctures, and develops innovative methodologies to understand reproduction in the context of everyday life in austerity. Using biographical vignettes from family ethnographies, themes of welfare restructuring, debt and care responsibilities emerge. Empirical insights explore social reproduction and defaulted futures, indebtedness and indecision as reproductive conjuncture, and incongruous biographies and absent possibilities. Conclusions call for further research on the relationship between reproductive futures and austerity, and methodological experimentation.


Characterization of novel mixed polyethyleneglycol modified liposomes.
In our previous paper, mixed polyetheleneglycol (PEG) modification of liposomes by a mixture of 1-monomethoxypolyethyleneglycol-2,3-distearoylglycerol (PEG-DSG) with short polyoxyethylene chain and PEG-DSG with long one was shown to increase fixed aqueous layer thickness (FALT) around the liposomal membrane, and this was useful in vivo. In this study, we investigated the characterization of mixed PEG modification of liposomes with different anchors (PEG2000-DSG and PEG2000-cholesterol (CHO)). When the liposomes was modified by a mixture of PEG2000-DSG and PEG2000-CHO, FALT was increased compared to that of each single PEG-lipids modification and the most suitable mix modification (PEG2000-DSG:PEG2000-CHO = 3:1) showed a maximum FALT. This phenomenon was speculated to be based on the difference in the insertion state of the PEG anchor unit in the liposomal membrane. PEG-CHO-modified liposomes (single or mixed PEG-modified liposomes) were easily incorporated into the liposomal membranes compared with that of single PEG-DSG-modified liposomes. Namely, it was considered that the cholesterol anchor as a single chain was able to be easily introduced, compared with the DSG anchor as two chains, and induced some interaction with both PEG modification. In conclusion, it is expected that novel PEG-modified liposomes with PEG2000-DSG and PEG2000-CHO (3:1) had superior physicochemical properties.


Simultaneous determination of optical loss, residual reflectance and transmittance of highly anti-reflective coatings with cavity ring down technique.
Cavity ring down (CRD) technique was employed to measure optical losses (absorption and scattering losses), residual reflectance and transmittance of anti-reflectively (AR) coated laser components with transmittance higher than 99.9%. By inserting the AR coated laser component with parallel optical surfaces into the ring-down cavity and measuring the ring-down time versus the angle of incidence with respect to the surface normal, the optical loss and residual reflectance of the laser component were determined respectively at normal and out-of-normal incidences with repeatability of part-per-million level. The transmittance was also determined simultaneously. Experimental results demonstrated that CRD is a simple, inexpensive and fast technique for highly accurate measurements of optical loss, residual reflectance, and transmittance of AR coated laser components widely used in high-power laser systems.


Osteonecrosis Mandibular Extended to Bisphosphonates: A Very Rare Extensive Case.
After the first report of bisphosphonate-related osteonecrosis of the jaw (BRONJ) in 2003, it has increased significantly since then. We report a very rare extensive case never seen before in our experience of bone exposure with necrosis reaching the mandibular inferior border. Although the treatment modalities are not yet established, most researchers have recommended conservative approaches. The surgery was to be as conservative as possible, with a resection of the mandibular range followed by reconstruction using titanium plate with space maintainer. The authors would like to share their approach, management, and awareness.


Derangements of mucosal growth and differentiation in small-intestinal diseases.
Physiologically, there is a balance of cell proliferation and exfoliation which maintains normal small-intestinal mucosal zonation with long villi and shallow crypts. In disease states and in the experimental animal this balance may be disturbed by numerous exogenous and endogenous factors, which may lead to three principally different responses: mucosal atrophy, mucosal hypertrophy, and mucosal transformation of the hyperregenerative type. The structural and functional characteristics of these different mucosal patterns are described, and their pathophysiologic relevance is discussed.


[Effects of preoperative administration of UFT in gastrointestinal cancer].
UFT, a combination antitumor drug consisting of 1 part Futraful and 4 parts Uracil, was administered preoperatively to 10 patients with gastric cancer, 9 patients with colo-rectal cancer and 1 patient with hepatocellular carcinoma. A pharmacokinetic study was then carried out after oral administration of 600 mg per day of UFT, measuring Uracil, Futraful and 5-FU levels in serum and tumor tissue. Preoperative total doses of UFT for gastric cancer were 3.0-11.4 g, for colo-rectal cancer 3.6-16.8 g and for hepatocellular carcinoma 8.4 g. Side effects, mainly gastrointestinal symptoms, were observed in 3 cases. Abnormalities of liver function test, depression of serum protein and bone marrow damage were observed in 4 cases. 5-FU concentration in the tumor tissue was higher than 0.05 mu/g in 15 of 19 patients (79%). This suggested that 5-FU was maintained in the tumor tissue for a longer period. However, it also suggested that the concentration of Uracil in the tumor tissue corresponded to the total dose of UFT as did the degree of side effects.


[Effect of HIF-2α mediated FoxM1 expression on proliferation of pulmonary artery smooth muscle cells in hypoxic rats].
Objective: To investigate the effect of hypoxia-inducible factor 2α (HIF-2α) gene on the expression of Forkhead box M1 (FoxM1) protein in the proliferation of hypoxic rat pulmonary artery smooth muscle cells (PASMC). Methods: HIF-2α overexpression lentiviral vector (LV-HIF-2α) and silencing RNA (siRNA) were constructed and transfected into rat PASMC under normoxia and hypoxia, respectively. The PASMC under normoxia were classified into normoxic control group, normoxia + LV-HIF-2α empty group, normoxia + LV-HIF-2α group; the PASMC under hypoxia were classified into hypoxic control group, hypoxia + siRNA-HIF-2α empty group, hypoxia + siRNA-HIF-2α group. The expression of HIF-2α and its downstream proteins FoxM1, cyclin D1 and Aurora A expressions were detected by Western blot. 5-Ethyny-2'-deoxyuridine (EdU) cell proliferation assay was used to evaluate the effect of overexpression and inhibition of HIF-2α expression on the proliferation of rat PASMC. Results: The expression of HIF-2α in normoxia + LV-HIF-2α group was significantly higher than that in normoxic control group and normoxia+LV-HIF-2α empty group (0.17±0.02 vs 0.09±0.01 and 0.07±0.00), while the expression of HIF-2α in PASMC of hypoxia + siRNA-HIF-2α group was significantly lower than that of hypoxic control group and hypoxia + siRNA-HIF-2α empty group (0.28±0.01 vs 0.35±0.02 and 0.30±0.01) (all P<0.05); the expression of FoxM1 protein, cyclinD1 and cell proliferation-related Aurora A protein in normoxia+LV-HIF-2α group were significantly higher than that in normoxic control group and normoxia+LV-HIF-2α empty group (0.40±0.03 vs 0.24±0.01 and 0.30±0.01, 0.22±0.02 vs 0.09±0.01 and 0.08±0.02, 0.29±0.02 vs 0.04±0.01 and 0.07±0.01, respectively) (all P<0.05); the expressions of FoxM1 protein, cyclinD1 and Aurora A protein in hypoxia + siRNA-HIF-2α group were significantly lower than those in hypoxic control group and hypoxia + siRNA-HIF-2α empty group (0.23±0.01 vs 0.36±0.02 and 0.32±0.01, 0.15±0.01 vs 0.31±0.01 and 0.28±0.03, 0.14±0.02 vs 0.33±0.03 and 0.27±0.02, respectively) (all P<0.05); the positive expression rate of EdU in the normoxic control group was significantly lower than that in the normoxia+LV-HIF-2α group [(30.77±2.43)% vs (55.56±3.01)%], while the hypoxic control group was significantly higher than the hypoxic+siRNA-HIF-2α group [(65.28±3.21)% vs (44.64±2.78)%] (both P<0.05). Conclusion: HIF-2α up-regulates the expression of FoxM1 and promotes the proliferation of pulmonary artery smooth muscle cells in hypoxic rats.


Pathological Features of the Unilateral Favorable Histology Nephroblastoma with Relapse.
To evaluate the pathological features of the primary lesion in patients with relapse of unilateral favorable histology nephroblastoma. Fifty-eight patients with unilateral favorable histology nephroblastoma who underwent initial nephrectomy before chemotherapy were categorized into one of two groups: the nonrelapsed group (n = 52) and the relapsed group (n = 6). The histological subtypes of both groups and pathological features of the relapsed group were re-evaluated retrospectively. The histological subtypes of all relapsed cases were classified as blastemal predominant. In three of six cases with relapse, sheets of spindle-shaped blastemal cells that were histologically reminiscent of synovial sarcoma were predominant (massive sarcomatoid pattern). The histological blastemal predominant subtype of nephroblastoma is a strong indicator of relapse. In particular, the blastemal predominant subtype with massive sarcomatoid pattern may have a higher risk of relapse.


Assessing outcomes of large-scale public health interventions in the absence of baseline data using a mixture of Cox and binomial regressions.
Large-scale public health interventions with rapid scale-up are increasingly being implemented worldwide. Such implementation allows for a large target population to be reached in a short period of time. But when the time comes to investigate the effectiveness of these interventions, the rapid scale-up creates several methodological challenges, such as the lack of baseline data and the absence of control groups. One example of such an intervention is Avahan, the India HIV/AIDS initiative of the Bill & Melinda Gates Foundation. One question of interest is the effect of Avahan on condom use by female sex workers with their clients. By retrospectively reconstructing condom use and sex work history from survey data, it is possible to estimate how condom use rates evolve over time. However formal inference about how this rate changes at a given point in calendar time remains challenging. We propose a new statistical procedure based on a mixture of binomial regression and Cox regression. We compare this new method to an existing approach based on generalized estimating equations through simulations and application to Indian data. Both methods are unbiased, but the proposed method is more powerful than the existing method, especially when initial condom use is high. When applied to the Indian data, the new method mostly agrees with the existing method, but seems to have corrected some implausible results of the latter in a few districts. We also show how the new method can be used to analyze the data of all districts combined. The use of both methods can be recommended for exploratory data analysis. However for formal statistical inference, the new method has better power.


Molecular Containers Derived from [60]Fullerene through Peroxide Chemistry.
Molecular containers can keep guest molecules in a confined space that is completely separated from the solution. They have wide potential applications, including selective trapping of reactive intermediates, catalysis within the cavity, and molecular delivery. Numerous molecular containers have been prepared through covalent bonds, metal-ligand interactions and H-bonding or hydrophobic interactions. Fullerenes are all-carbon molecules with a spherical structure. Partial opening of the cage structure results in open-cage fullerenes, which can serve as molecular containers for various small molecules and atoms. Compared with classical molecular containers, open-cage fullerenes exhibit some unusual phenomena because of the unique structure of the fullerene cage. The synthesis of an open-cage fullerene with a large enough orifice as a molecular container requires consecutive cleavage of multiple fullerene skeleton bonds within a local area on the cage surface. In spite of the difficulty, remarkable progress has been achieved. Several reactions have been reported to cleave fullerene C-C bonds selectively to form open-cage fullerenes, some of which have been successfully used as molecular containers for molecules such as H2O. The size and shape of the orifice play a key role in the encapsulation of the guest molecule. To date the focus in this area has been the preparation of open-cage fullerenes and encapsulation of small molecules. Little information has been reported about the functional properties of these host-guest systems. Potential applications of these systems need to be explored. This Account mainly presents our results on the encapsulation of small molecules in open-cage fullerenes prepared in my group. The preparation of our open-cage fullerenes is based on fullerene-mixed peroxides, which are briefly mentioned herein. The encapsulation and release of a single molecule of water is discussed in detail. Quantitative water encapsulation was achieved by heating the open-cage fullerene in a homogeneous CDCl3/H2O/EtOH mixture at 80 °C for 18 h. The kinetics of the water release process was studied by blackbody IR radiation-induced dissociation (BIRD) and theoretical calculations. The trapped water could also be released by H-bonding with HF. To control the encapsulation and release processes, we prepared open-cage fullerenes with a switchable stopper on the rim of the orifice. Besides H2O, encapsulations of H2, HF, CO, O2, and H2O2 were also achieved by using different open-cage fullerenes. The encapsulation of CO is quite unusual in that the trapped CO is derived from a fullerene skeleton carbon that was pushed into the cavity by oxidation under ambient conditions at room temperature. The trapped O2/H2O2 could be released slowly under mild conditions, and these systems are now being studied as a new type of oxygen-releasing materials for biomedical research. The present results demonstrate that open-cage fullerenes are suitable molecular containers for small molecules. Our future work will focus on optimizing the conditions for the preparation of open-cage fullerenes and applications of open-cage fullerenes in areas such as oxygen delivery for photodynamic therapy.


Catecholaminergic inputs to aromatase cells in the canary auditory forebrain.
The caudomedial nidopallium in songbirds is a specialized forebrain auditory region involved in the processing of species-typical vocalizations. It receives a prominent catecholaminergic projection with many fibers forming basket-like structures around non-immunoreactive cells. We investigated in male canaries the anatomical relationship between tyrosine hydroxylase and cells immunoreactive for the steroid metabolizing enzyme, aromatase, in the caudomedial nidopallium using double-label immunocytochemistry. Fibers immunoreactive for tyrosine hydroxylase established numerous close contacts with aromatase-immunoreactive cells and often encircled these cells to form basket-like structures. Aromatase containing cells in the caudomedial nidopallium are therefore a major target of catecholaminergic inputs in canary. Interactions between catecholaminergic systems and aromatase in the caudomedial nidopallium may provide one mechanism for the regulation of estrogens involved in song perception and memorization.


Interferon induction by STING requires its translocation to the late endosomes.
To combat microbial infections, mammalian cells use a variety of innate immune response pathways to induce synthesis of anti-microbial proteins. The cGAS/STING pathway recognizes cytoplasmic viral or cellular DNA to elicit signals that lead to type I interferon and other cytokine synthesis. cGAMP, synthesized by DNA-activated cGAS, activates the ER-associated protein, STING, which oligomerizes and translocates to other intracellular membrane compartments to trigger different branches of signaling. We have reported that, in the ER, EGFR-mediated phosphorylation of Tyr245 of STING is required for its transit to the late endosomes, where it recruits and activates the transcription factor IRF3 required for IFN induction. In the current study, we inquired whether STING Tyr245 phosphorylation per se or STING's location in the late endosomes was critical for its ability to recruit IRF3 and induce IFN. Using pharmacological inhibitors or genetic ablation of proteins that are essential for specific steps of STING trafficking, we demonstrated that the presence of STING in the late endosomal membranes, even without Tyr245 phosphorylation, was sufficient for IRF3-mediated IFN induction.


Association between gestational diabetes and perinatal depressive symptoms: evidence from a Greek cohort study.
Aim The aim of the present study was to assess the association of gestational diabetes mellitus (GDM) with prenatal and postnatal depressive symptoms in a sample of pregnant women in Greece. Earlier research supports a relationship between depression and diabetes, but only a few studies have examined the relationship between GDM and perinatal depressive symptomatology. A total of 117 women in their third trimester of pregnancy participated in the study. Demographic and obstetric history data were recorded during women's third trimester of pregnancy. Depressive symptoms were assessed with the validated Greek version of the Edinburg Postnatal Depression Scale (EPDS) at two time points: on the third trimester of pregnancy and on the first week postpartum. Findings Prevalence of GDM was 14.5%. Probable diagnosis of depression occurred for 12% of the sample during the antenatal assessment and 15.1% in the postpartum assessment. In the first week postpartum, women with GDM had significantly higher postpartum (but no antenatal) EPDS scores compared with the non-GDM cohort. In conclusion, GDM appears to be associated with depressive symptoms in the first week postpartum. Clinical implications and recommendations for future research are discussed, emphasizing the importance of closely monitoring women with GDM who seem more vulnerable to developing depressive symptomatology during the postnatal period.


Electrodiffusion of lipids on membrane surfaces.
Lateral translocation of lipids and proteins is a universal process on membrane surfaces. Local aggregation or organization of lipids and proteins can be induced when the random lateral motion is mediated by the electrostatic interactions and membrane curvature. Although the lateral diffusion rates of lipids on membranes of various compositions are measured and the electrostatic free energies of predetermined protein-membrane-lipid systems can be computed, the process of the aggregation and the evolution to the electrostatically favorable states remain largely undetermined. Here we propose an electrodiffusion model, based on the variational principle of the free energy functional, for the self-consistent lateral drift-diffusion of multiple species of charged lipids on membrane surfaces. Finite sizes of lipids are modeled to enforce the geometrical constraint of the lipid concentration on membrane surfaces. A surface finite element method is developed to appropriate the Laplace-Beltrami operators in the partial differential equations of the model. Our model properly describes the saturation of lipids on membrane surfaces, and correctly predicts that the MARCKS peptide can consistently sequester three multivalent phosphatidylinositol 4,5-bisphosphate lipids through its basic amino acid residues, regardless of a wide range of the percentage of monovalent phosphatidylserine in the membrane.


Pd-Catalyzed Three-Component Reaction of Anilines, Ethyl Vinyl Ether, and Nitro-Paraffin: Assembly of β-Nitroamines.
A novel palladium-catalyzed amination and nitration of ethyl vinyl ether for the construction of β-nitroamine derivatives under mild conditions has been developed. This transformation provides a new strategy for the installation of amino and nitro from aromatic amines and nitro-paraffin into alkenes. Morpholine resulted in the aza-Henry reaction, while DABCO led to the unexpected rearrangement.


Study on Al-Si alloy-based nanocomposites with dispersed detonation nanodiamonds.
Al-Si alloy-based nanocomposites with dispersed detonation nanodiamonds are fabricated by a powder metallurgy method. Rapid-solidified Al-Si alloy powder and detonation nanodiamond of 1% by volume are mechanically mixed at 500 rpm for 4 h; the nanoadditives used above are as-synthesized and purified detonation nanodiamonds. The obtained Al-Si nanocomposite mixtures are consolidated at 773 K by vacuum-hot pressing. The microstructural observations indicate that the fabricated Al-Si nanocomposites have fine grain structures with dispersed eutectic Si particles and detonation nanodiamonds in the grains; structural changes in the dispersed nanodiamonds are not observed. The mechanical and friction properties of the fabricated Al-Si nanocomposites with dispersed detonation nanodiamonds are investigated by carrying out indentation and friction measurements. It is observed that the dispersion of detonation nanodiamonds in the Al-Si alloy matrix improves its mechanical and friction properties. In particular, the dispersion of the purified detonation nanodiamond enhances the elastic modulus of the nanocomposite to a greater extent than that of the as-synthesized detonation nanodiamond with graphitic shell structure; in contrast, the use of the as-synthesized detonation nanodiamond reduces friction to a greater extent than the use of the purified detonation nanodiamond.


Optimizing thiophosphorylation in the presence of competing phosphorylation with MALDI-TOF-MS detection.
Thiophosphorylation provides a metabolically stable, chemically reactive phosphorylation analogue for analyzing the phosphoproteome in vitro and in vivo. We developed a MALDI-TOF-MS based assay for optimizing thiophosphopeptide production by a kinase even in the presence of Mg(2+) and ATP. We found that Abl kinase thiophosphorylation rates can be "rescued" using Mn(2+) in the presence of Mg(2+). Under our ideal conditions, titration of Mn(2+) and ATPgammaS in the presence of Mg(2+) allowed relatively rapid, highly specific thiophosphorylation by Abl tyrosine kinase, both as purified enzyme and in complex cell extracts.


Prevalence, Outcomes, and Risk Factors of New-Onset Atrial Fibrillation in Critically Ill Patients.
The purpose of this article is to systematically evaluate the prevalence, outcomes, and risk factors of new-onset atrial fibrillation (AF) in critically ill patients.Medline, Embase, Science Citation Index, Wanfang, CNKI, and Wiley Online Library were thoroughly searched to identify relevant studies. Studies were assessed for methodological quality using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. Odds ratio (OR) and weighted mean difference (WMD) with 95% confidence interval (CI) were used to assess the strength of the association. Heterogeneity, subgroup, sensitivity analyses, and publication bias were conducted.A total of 25 studies were included. The prevalence of new-onset AF ranged from 4.1% to 46%.The random-effects pooled prevalence was 10.7%. The pooled result jumped up to 35.8% in patients with septic shock. Pooled analysis showed significant associations between new-onset AF with intensive care unit (ICU) mortality and in-hospital mortality over those patients without AF (OR = 3.11; 95%CI 2.45-3.96 and OR = 1.63; 95%CI 1.27-2.08). The pooled analysis also indicated that both ICU and hospital length of stay are longer in patients with new-onset AF than those without AF (WMD = 1.87; 95%CI 0.89-2.84 and WMD = 2.73; 95%CI 0.77-4.69). Independent risk factors included increasing age, shock, sepsis, use of a pulmonary artery catheter and mechanical ventilation, fluid loading, and organ failures.New-onset AF incidence rate is high in critically ill patients. New-onset AF is associated with worse outcomes. Further studies should be done to explore how to prevent and treat new-onset AF in critically ill patients.


Oxidative-stress resistance mutants of Helicobacter pylori.
Within a large family of peroxidases, one member that catalyzes the reduction of organic peroxides to alcohols is known as alkyl hydroperoxide reductase, or AhpC. Gene disruption mutations in the gene encoding AhpC of Helicobacter pylori (ahpC) were generated by screening transformants under low-oxygen conditions. Two classes of mutants were obtained. Both types lack AhpC protein, but the major class (type I) isolated was found to synthesize increased levels (five times more than the wild type) of another proposed antioxidant protein, an iron-binding, neutrophil-activating protein (NapA). The other class of mutants, the minor class (type II), produced wild-type levels of NapA. The two types of AhpC mutants differed in their frequencies of spontaneous mutation to rifampin resistance and in their sensitivities to oxidative-stress chemicals, with the type I mutants exhibiting less sensitivity to organic hydroperoxides as well as having a lower mutation frequency. The napA promoter regions of the two types of AhpC mutants were identical, and primer extension analysis revealed their transcription start site to be the same as for the wild type. Gene disruption mutations were obtained in napA alone, and a double mutant strain (ahpC napA) was also created. All four of the oxidative-stress resistance mutants could be distinguished from the wild type in oxygen sensitivity or in some other oxidative-stress resistance phenotype (i.e., in sensitivity to stress-related chemicals and spontaneous mutation frequency). For example, growth of the NapA mutant was more sensitive to oxygen than that of the wild-type strain and both of the AhpC-type mutants were highly sensitive to paraquat and to cumene hydroperoxide. Of the four types of mutants, the double mutant was the most sensitive to growth inhibition by oxygen and by organic peroxides and it had the highest spontaneous mutation frequency. Notably, two-dimensional gel electrophoresis combined with protein sequence analysis identified another possible oxidative-stress resistance protein (HP0630) that was up-regulated in the double mutant. However, the transcription start site of the HP0630 gene was the same for the double mutant as for the wild type. It appears that H. pylori can readily modulate the expression of other resistance factors as a compensatory response to loss of a major oxidative-stress resistance component.


Frequency of Head and Neck Squamous Cell Carcinomas and Related Variables in Southern Iran (Ahvaz City): 10-Year Retrospective Study
Objective: Squamous cell carcinoma (SCC) is a life threatening lesion but there has been only limited research about its frequency in Iran. The aim of this study was to evaluate the frequency of squamous cell carcinoma of the head and neck in the records of the pathology department of Imam Khomeini hospital in Ahvaz between 2005 and 2015. Methods: The retrospective and cross-sectional study was conducted using 55,708 medical records of cancer throughout the body, accumulated in the pathology department of Imam Khomeini in Ahvaz in the designated period. Information about age, gender, site of involvement, histological characteristics, status of lymph node metastasis, smoking habit, family history, job and education level was extracted and data were analyzed with the Chi-square test with SPSS version 22. Result: Of the total of 55,708 records, 582 patients (1.04%) had head and neck squamous cell carcinomas. The male to female ratio was 2.85. The frequencies in the head, mouth and neck were 28.7%, 22% and 49.3% respectively. Significant relationships between being male and location (neck) (p = 0.002), age (60 to 80 years old) and being a farmer (p = 0.001) was observed. The most important correlated risk factors were: smoking, sunlight exposure, rural residence, job and education level. Conclusion: Head and neck squamous cell carcinomas were found to account for 1.04% of all cancers in Ahvaz, one of the southern provinces of Iran.


Genetic characterization of Erwinia amylovora strains by random amplified polymorphic DNA fragments (RAPD).
Erwinia amylovora is the causative agent of fire blight, a destructive disease of rosaceous plants subjected to strict quarantine regulations worldwide. Previous studies showed that the population of E. amylovora in Romania is homogenous in its biochemical and serological characteristics, despite the different strains' geographical and host origin. The aim of the present study was to establish and test a typing method to quantify genetic diversity among the Romanian strains of this plant pathogen. Fourteen strains isolated from different hosts and geographical locations in Romania were examined by random amplified polymorphism DNA (RAPD) fragment analysis with two ten-base primers. This molecular method has not revealed any polymorphism, producing the same amplification patterns for all tested strains. Clustering of strains in the resulting dendrogram was not correlated with host, or region of isolation. The RAPD technique did not allow the detection of genetic markers in E. amylovora strains isolated in Romania and proved not to be discriminating among strains of this pathogen. The results presented in this study suggest that the population of E. amylovora in Romania is homogenous.


Coeliac disease presenting as chronic cough in an 8-year-old child.
Patients with the 'classical' gastrointestinal symptoms of coeliac disease (CD) are usually readily diagnosed and treated with a gluten exclusion diet. However, the advent of sensitive serological investigations has revealed that over half of childhood CD remains asymptomatic or presents with more subtle non-gastrointestinal symptoms, with a significant risk to the health of undiagnosed children. In view of its changing presentation there is an increasing need for clinicians to have a low threshold to investigate patients for this disease. Rare cases of CD associated with respiratory symptoms have been reported. The authors report an interesting case presenting as chronic cough in an otherwise asymptomatic 8-year-old girl. As a result of having a low threshold of suspicion for underlying CD, a diagnosis has been made and the long-term health risks of undiagnosed disease have been improved in both the patient and her immediate family.


The economic impact of Plasmodium falciparum malaria on education investment: a Pacific Island case study.
A small but intensive study was carried out adopting a simple method which attempts to quantify the economic consequences Plasmodium falciparum malaria on education investment through school pupil absenteeism in a community in Solomon Islands. In a randomized sample of 4,920 cases of P. falciparum malaria in a community, 2,886 occurred in children of primary school age group of 7 to 13 years. On average a case gave rise to a mean school absenteeism of 5.3 days. In the final analysis a total of 11,028 pupil days schooling were lost due to the sampled cases of malaria caused by the species. This is equivalent to 55.14 school pupil years as a child is expected to attend school for 200 days in a year. A primary school teacher with an average annual salary of US$3,990.00 is expected to teach 6,500 school pupil days a year. When this is adopted as an economic indicator for investment in education the loss is calculated to be US$6,769.57 or equivalent to US$1.38 per case. When this is applied nationally, assuming that rates are similar for 79,203 cases of P. falciparum reported in 1990, the total consequence for investment in education is US$108,966.00, which is equivalent to 27.31 teachers being paid for not teaching, an unacceptable impact for a small nation like the Solomon Islands.


The Inflammatory Potential of the Diet at Midlife Is Associated with Later Healthy Aging in French Adults.
While low-grade chronic inflammation has been suggested as a major modulator of healthy aging (HA), no study has yet investigated the link between the inflammatory potential of the diet and multidimensional concepts of HA. We aimed to evaluate the association between the inflammatory potential of the diet at midlife, as measured by the Dietary Inflammatory Index (DII), and HA assessed 13 y later. We analyzed data from 2796 participants in the French Supplémentation en Vitamines et Minéraux Antioxydants (SU.VI.MAX) study aged 45-60 y at baseline (1994-1995) and initially free of diabetes, cardiovascular disease, and cancer. During the trial phase of the study (1994-2002), participants received either a placebo or a daily nutritional dose of antioxidant supplement (120 mg vitamin C, 6 mg β-carotene, 30 mg vitamin E, 100 μg Se, 20 mg Zn). HA was assessed in 2007-2009, and defined as having no major chronic disease, good physical and cognitive functioning, independence in daily activities, no depressive symptoms, good social health, good overall self-perceived health, and no function-limiting pain. The DII was calculated based on repeated baseline 24-h dietary records. Its association with HA was assessed by robust-error-variance Poisson regression, providing RR estimates. After adjustment for potential confounders, higher DII scores (reflecting a more proinflammatory diet), were associated with a decreased likelihood of HA: RRtertile 3/tertile 1 = 0.85 (95% CI: 0.74, 0.99); P-trend = 0.03. Secondary analyses revealed that this association was only significant among participants who had been in the placebo group during the trial phase: RRtertile 3/tertile 1 = 0.80 (95% CI: 0.64, 1.00); P-trend = 0.04. This study suggests that a proinflammatory diet may lower the probability of overall HA. The SU.VI.MAX trial was registered at www.clinicaltrials.gov as NCT00272428.


Nephrotic syndrome associated with agnogenic myeloid metaplasia.
Extramedullary hematopoiesis being an important feature of agnogenic myeloid metaplasia (AMM), a chronic myeloproliferative disease of clonal origin, may affect the kidneys, but this condition is usually asymptomatic. Until now, there is only one reported case of nephrotic syndrome associated with AMM. We present a patient with AMM who had nephrotic syndrome and whose renal biopsy revealed membranous glomerulonephritis together with renal extramedullary hematopoiesis.


Teaching reproductive options through the use of fiction: the Cider House Rules project.
Alternative teaching strategies such as storytelling and the critical reading of literature are thought to help students develop their critical thinking, emotional intelligence, and cultural sensitivity and thereby better understand the context in which their patients live and make decisions. Such teaching methods are ideally suited for examining morally complex issues such as reproductive options. This article describes an alternative approach to teaching the complex personal, social, and moral issues surrounding the topic of reproductive options. The critical reading of the book, The Cider House Rules, provides a unique opportunity for students to obtain insight and understanding of the complex circumstances under which women and their families make reproductive decisions.


Changes in enzymatic activity of small intestine and kidney of rats by a methionine deficient diet.
The effect of methionine dietary deficiency on food intake, weight gain, liver and kidney weight, feed conversion rate, protein efficiency ratio, maltase and leucineaminopeptidase (LAPase) activities of the intestinal mucosa as well as renal LAPase activity was studied. Three groups of female Wistar rats, weighing between 40-60 g, were fed for 25 days on either Diet A (casein supplemented with 0.6% DL-methionine), Diet B (amino acid mixture simulating casein also supplemented with 0.6% methionine) or Diet C (amino acid mixture with 0.67% methionine deficiency with respect to Diet A). The results show no significant differences in either growth or enzymatic activity between the rats fed on Diet A and those on Diet B. The animals fed on Diet C show an increase in intestinal (P less than 0.01, vs Diet B) and renal (P less than 0.005, vs Diet A) LAPase activity, although intestinal maltase activity remained unchanged. Food intake, weight gain, organ weight and nutritional parameters obtained in rats fed on Diet C showed no statistically significant changes, with the exception of kidney weight which decreased (P less than 0.005) when compared to those fed on Diet B.


Two-Year Follow-Up of Vascular Events in Peripheral Arterial Disease Treated With Antiplatelet Agents: A Prospective Observational Multicenter Cohort Study (SEASON).
The present analysis was intended to evaluate the real-world management of peripheral arterial disease (PAD) in Asia, and to explore cardiovascular events in patients with PAD undergoing antiplatelet therapy over 2 years of follow-up. The Surveillance of cardiovascular Events in Antiplatelet-treated arteriosclerosis Obliterans patients in JapaN (SEASON) registry is a prospective observational multicenter study of cardiovascular events in antiplatelet-treated patients with PAD in Japan. The SEASON registry included 11,375 patients who were scheduled to receive treatment for PAD. Two analysis populations were defined: a real-world population (RWP; n = 10,322) and a definite PAD population (DPP; n = 3992) who had ankle-brachial pressure index (ABPI) <0.9 and intermittent claudication, or a history of lower limb revascularization. The primary outcome measure was the rate of the composite of cerebrovascular, cardiovascular, and peripheral vascular events. The composite event rates (95% confidence interval) were 3.28 (3.00-3.57) and 5.71 (5.13-6.34) events per 100 patient-years in the RWP and DPP groups, respectively. Fontaine IV classification and ABPI <0.4 at baseline were both identified as strong risk factors for vascular events. These findings contribute to understanding the situation for real-world patients with PAD receiving antiplatelet therapy.


[Current basic understanding and clinical application of mesenchymal stromal/stem cells].
Mesenchymal stromal/stem cells (MSCs) exhibit various biological characteristics, including immunomodulation, tissue regeneration, anti-inflammation, and hematopoietic support. Extensive efforts have been made toward the development of cell therapy using MSCs to treat various diseases. In Japan, off-the-shelf allogeneic human bone marrow-derived MSC products from third-party donors are clinically available for treating patients with steroid-resistant/refractory acute graft-versus-host disease (GVHD). In this manuscript, we present an overview of the current status of clinical development of MSC-based cell therapy and the basic understanding of MSCs. We also introduce a novel approach to obtain the anti-GVHD effect utilizing bone marrow MSC-derived extracellular vesicles.


rCBF/SPECT in the evaluation of inner-city minority patients with a history of impaired memory: a pilot blind read pre- and poststudy.
Eight patients (seven women), mean +/- SD T1 age 68.57 +/- 12.43 years, average educational level 5.83 +/- 3.70 years, had two Tc-99m ECD SPECT examinations separated by an average 8.49 +/- 5.59 months. Patients were imaged using standard Harlem Hospital acquisition and processing protocols with approximately 30 mCi of ECD on a Prism 3000 triple head gamma camera. Images were interpreted by an independent reader blinded to the patients' clinical history and imaging date. T1 psychiatric diagnosis was seven Alzheimer's dementia (AD) and one depression. Eight T1 images were interpreted as abnormal, six indicative of AD. Binomial 95% two-tail confidence interval for T1 agreement between diagnosis and interpretation was 0.25 0.63 0.92. T2 diagnosis was seven AD and one none. Seven T2 images were abnormal and indicative of AD, and one was normal. T2 confidence interval was 0.34 0.75 0.97. These findings suggest SPECT's value in assessing AD in uneducated socioeconomically disadvantaged geriatric patients.


Effects of fluoridated drinking water on dental caries in Australian adults.
Systematic reviews produce conflicting conclusions regarding dental caries-preventive effects of water fluoridation in adults. The authors investigated the relationship using data from the nationally representative 2004-2006 Australian National Survey of Adult Oral Health. Effects were compared between the pre-fluoridation cohort born before 1960 (n = 2,270) and the cohort born between 1960 and 1990 (n = 1,509), when widespread implementation of fluoridation increased population coverage from < 1% to 67%. Residential history questionnaires determined the percentage of each person's lifetime exposed to fluoridated water. Examiners recorded decayed, missing, and filled teeth (DMF-Teeth) and decayed and filled tooth surfaces (DF-Surfaces). Socio-demographic and preventive dental behaviors were included in multivariable least-squares regression models adjusted for potential confounding. In fully adjusted models, > 75% of lifetime exposure to fluoridation relative to < 25% of lifetime exposure was associated with 11% and 10% fewer DMF-Teeth in the pre-1960 (p < .0001) and 1960-1990 cohorts (p = .018), respectively. Corresponding reductions in DF-Surfaces were 30% (p < .001) and 21% (p < .001). Findings for intermediate fluoridation exposure suggested a dose-response relationship. Results were consistent in sensitivity analyses accounting for missing data. In this nationally representative sample of Australian adults, caries-preventive effects of water fluoridation were at least as great in adults born before widespread implementation of fluoridation as after widespread implementation of fluoridation.


An investigation of resorption and tissue reaction after subcutaneous implantation of collagen based membrane materials in rats.
This study was undertaken to assess histologically the response to collagen based membrane materials that might be used for guided tissue regeneration (GTR) procedures, using a subcutaneous model on the dorsal surface of the rat. The commercially available materials included absorbable type I bovine collagen barrier, fascia lata, fascia temporalis and dura mater membranes. In the study 20 Wistar rats were used 80 implant materials were placed under general anaesthesia. Animals were sacrificed 7, 14, 28 and 42 days post-implantation. The specimens were assessed histologically for the composition of the tissue surrounding the membranes, the types of cells in infiltrate and the degree of resorption. It was concluded that these membrane materials were well tolerated and were gradually resorbed. Light microscopic examination showed that the type I bovine collagen and fascia lata were resorbed faster but fascia temporalis and dura mater were resorbed more slowly at 42 days. In addition the resorption process was continuing and these materials were evident histologically at 42 days.


[Löffler endocarditis fibroplastica with simultaneous infectious endocarditis].
The clinical and immunological 8-year follow-up of a 45-year old female with hypereosinophilic syndrome and cardiac involvement of Löffler's fibroplastic endocarditis which was complicated by infective endocarditis during immunosuppressive treatment is presented. All 3 stages of the disease were documented by clinical and histologic data: stage 1 by biopsy proven eosinophilic myocarditis and arteritis, stage 2 with Berlin blue positive parietal thrombosis, and the fibrotic features of stage 3 both by fibrosis in the latest biopsies and by echocardiography. It was remarkable, however, that this classic clinical case of Löffler's endocarditis lacked a few serological markers postulated to be found regularly, e.g., a positive staining for the cationic protein and major ribonucleases. Instead, the patient demonstrated all the immunological features of autoreactive myocarditis with cytolytic, complement fixing antimyolemmal antibodies. After an initial loading dose of 120 mg prednisolone per day for 6 weeks (11/1986), the steroid dosage was reduced to 40 mg (12/1986) and diminished to 15 mg/day in 1988 to 1989. Finally, the patient was on 4 mg prednisolone per day for almost 4 years. In 1987, azathioprine was added in the dose of 150 mg/day for 6 weeks. In 3/1994 the patient developed infective endocarditis with streptococcus sanguis and presented with dyspnoea. By echocardiography a large floating structure was diagnosed on the anterior mitral leaflet and the left atrium was enlarged by severe mitral regurgitation. Infective endocarditis was successfully treated with antibiotics, but mitral regurgitation made valve replacement obligatory.


Lysine-phosphatidylcholine adducts in kringle V impart unique immunological and potential pro-inflammatory properties to human apolipoprotein(a).
Lipoprotein(a), Lp(a), an athero-thrombotic risk factor, reacts with EO6, a natural monoclonal autoantibody that recognizes the phophorylcholine (PC) group of oxidized phosphatidylcholine (oxPtdPC) either as a lipid or linked by a Schiff base to lysine residues of peptides/proteins. Here we show that EO6 reacts with free apolipoprotein(a) apo(a), its C-terminal domain, F2 (but not the N-terminal F1), kringle V-containing fragments obtained by the enzymatic digestion of apo(a) and also kringle V-containing apo(a) recombinants. The evidence that kringle V is critical for EO6 reactivity is supported by the finding that apo(a) of rhesus monkeys lacking kringle V did not react with EO6. Based on the previously established EO6 specificity requirements, we hypothesized that all or some of the six lysines in human kringle V are involved in Schiff base linkage with oxPtdPC. To test this hypothesis, we made use of a recombinant lysine-containing apo(a) fragment, rIII, containing kringle V but not the protease domain. EO6 reacted with rIII before and after reduction to stabilize the Schiff base and also after extensive ethanol/ether extraction that yielded no lipids. On the other hand, delipidation of the saponified product yielded an average of two mol of phospholipids/mol of protein consistent with direct analysis of inorganic phosphorous on the non-saponified rIII. Moreover, only two of the six theoretical free lysine amino groups per mol of rIII were unavailable to chemical modification by 2,4,6-trinitrobenzene sulfonic acid. Finally, rIII, like human apo(a), stimulated the production of interleukin 8 in THP-1 macrophages in culture. Together, our studies provide evidence that in human apo(a), kringle V is the site that reacts with EO6 via lysine-oxPtdPC adducts that may also be involved in the previously reported pro-inflammatory effect of apo(a) in cultured human macrophages.


The role of peptide motifs in the evolution of a protein network.
Naturally occurring proteins in cellular networks often share peptide motifs. These motifs have been known to play a pivotal role in protein interactions among the components of a network. However, it remains unknown how these motifs have contributed to the evolution of the protein network. Here we addressed this issue by a synthetic biology approach. Through the motif programming method, we have constructed an artificial protein library by mixing four peptide motifs shared among the Bcl-2 family proteins that positively or negatively regulate the apoptosis networks. We found one strong pro-apoptotic protein, d29, and two proteins having moderate, but unambiguous anti-apoptotic functions, a10 and d16, from the 28 tested clones. Thus both the pro- and anti-apoptotic modulators were present in the library, demonstrating that functional proteins with opposing effects can emerge from a single pool prepared from common motifs. Motif programming studies have exhibited that the annotated function of the motifs were significantly influenced by the context that the motifs embedded. The results further revealed that reshuffling of a set of motifs realized the promiscuous state of protein, from which disparate functions could emerge. Our finding suggests that motifs contributed to the plastic evolvability of the protein network.


Setting apart the amateur from the professional: maintaining the value of standardised representational photography.
The purpose of this paper is to discuss the importance of standard representational photography in clinical photography and its aid in maintaining the gold standard in the medical illustration profession. it is important that professionals are aware of potential threats to good practice with many areas identified in the article.


Morphovolumetric changes after EMDR treatment in drug-naïve PTSD patients.
Few studies have investigated the effects of efficacious psychotherapy on structural alterations of discrete brain regions associated with posttraumatic stress disorder (PTSD). We therefore proposed to evaluate the neurobiological effects of eye movement desensitization and reprocessing (EMDR) on 19 patients with drug-naïve PTSD without comorbidity, matched with 19 untreated healthy controls. We administered the Clinician Administered PTSD Scale (CAPS) and conducted brain MRI measurements (with Optimized Voxel-Based Morphometry). Patients received 12 EMDR sessions over three months. Then patients and controls were reassessed. At baseline, grey matter volume (GMV) differed significantly between patients and controls (F 1,35 =3.674; p=.008; η 2=.298). Analyses of 3-month scans showed no changes for controls, while significant changes were highlighted for patients post-EMDR, with a significant increase in GMV in left parahippocampal gyrus, and a significant decrease in GMV in the left thalamus region. The diagnosis of PTSD was effectively eliminated in 16 of 19 patients, reflected in a significant improvement on the CAPS (t(35)=2.132, p<.004). Results indicated post-EMDR changes for patients in brain morphology. We discuss whether EMDR's mechanism of action may work at the level of the thalamus, an area implicated in PTSD pathology.


Effect of ivelip and sodium nitroprusside on 5-HT, glutathione and lipid peroxidation in normal and malnourished rat brain.
We examined the effect of experimental malnutrition and diet supplementation of parameters of central nervous system damage. Wistar rats were fed during 30 days and classified as malnourished (MN, 7% protein content diet) or well-nourished (WN, 23% protein content diet), were grouped and treated as follows: I-control; II-SNP (20 microg/kg); IIl-Ivelip (280 mg/kg) and IV-Ivelip + sodium nitroprusside (SNP). Levels of lipid peroxidation (TBARS), glutathione (GSH), tryptophan (Trp) and serotonin (5-HT) were assessed in brain by liquid chromatography. TBARS and GSH levels increased significantly (p < 0.05) in MN vs. WN rats that did not receive Ivelip. No significant differences were observed in TBARS and GSH among rats that received Ivelip or SNP. The weight of rats decreased significantly (p < 0.05) in all MN groups in relation to the WN groups. Hemoglobin (Hb) levels increased significantly (p < 0.05) in MN and WN groups that received Ivelip. 5-HT levels increased significantly (p < 0.05) in all MN groups. Trp levels increased significantly (p < 0.05) in the WN + Ivelip group vs. control. Early malnutrition induces changes in the metabolism of biogenic amines and this condition may promote oxidative injury of the brain.


Three Learning Organizations in Cataract Surgery: The Example of Intracameral Antibiotic Injection.
The recent systematic adoption of intracameral antibiotic injection during cataract surgery in Sweden, India, and the US serves as a model for the successful transitioning of local quality improvement initiatives to organization-wide implementation. Although the delivery of eye care in the 3 countries is distinctly organized with differing governances and technological infrastructure, each contains elements of a learning organization (ie, an organization that has adopted a culture of creating, acquiring, and transferring knowledge into practice through system-level and clinician-level change). We describe a retrospective and organizational implementation study of intracameral antibiotic injection in Sweden, through the efforts of the National Cataract Registry; in the US by Kaiser Permanente; and in India by the Aravind Eye Hospital System. Leadership structure, training in problem solving, benchmarking, sharing of technical knowledge, and data and workforce engagement are compared. Each of the 3 organizations share the key elements of effective leadership, which values the exchange of ideas in the workforce, training and resourcing for change, and information management in the form of benchmarking and data sharing. In the case of intracameral antibiotic injection, a new technique was identified to improve quality and safety with a reduction in infections as evidence of the success of the programs. Committing to a culture of collective learning, and leveraging each stakeholder's personal investment, health-care systems may improve care delivery and set new benchmarks in quality and safety.


[Biosynthesis and purification of human beta2-adrenergic receptor expressed in methylotrophic yeast Pichia pastoris].
Human beta2-adrenergic receptor is one of the most studied G-protein-coupled receptors. It plays a key role in autonomic nervous system and is a drug target in cardiovascular and pulmonary diseases. Despite the fact that its crystal structure was revealed, a physiological role and molecular mechanisms of its action remain largely unknown. We designed the construct pVR2ADRH, which contained the gene for human beta2-adrenergic receptor with a polyhistidine tag C-terminal extension. The recombinant DNA was used for transformation of the GS115 strain of Pichia pastoris. The heterologous expression level obtained was about 20 mg/l. The receptor was extracted from membrane fraction and was purified by metal-affinity and ion-exchange chromatography. The active receptors were isolated by alprenolol-sepharose CL-4B. The resulting level of purified human beta2-adrenergic receptor was approximately 1 mg per liter of culture. The homogeneity of the protein sample was confirmed by a dynamical light scattering analysis of the receptor's micellar solution.


Dynamics in the plastic crystalline phase of cyanocyclohexane and isocyanocyclohexane probed by 1H field cycling NMR relaxometry.
Proton Field-Cycling (FC) nuclear magnetic resonance (NMR) relaxometry is applied over a wide frequency and temperature range to get insight into the dynamic processes occurring in the plastically crystalline phase of the two isomers cyanocyclohexane (CNCH) and isocyanocyclohexane. The spin-lattice relaxation rate, R1(ω), is measured in the 0.01-30 MHz frequency range and transformed into the susceptibility representation χNMR ″ω=ωR1ω. Three relaxation processes are identified, namely, a main (α-) relaxation, a fast secondary (β-) relaxation, and a slow relaxation; they are very similar for the two isomers. Exploiting frequency-temperature superposition, master curves of χNMR ″ωτ are constructed and analyzed for different processes. The α-relaxation displays a pronounced non-Lorentzian susceptibility with a temperature independent width parameter, and the correlation times display a non-Arrhenius temperature dependence-features indicating cooperative dynamics of the overall reorientation of the molecules. The β-relaxation shows high similarity with secondary relaxations in structural glasses. The extracted correlation times well agree with those reported by other techniques. A direct comparison of FC NMR and dielectric master curves for CNCH yields pronounced difference regarding the non-Lorentzian spectral shape as well as the relative relaxation strength of α- and β-relaxation. The correlation times of the slow relaxation follow an Arrhenius temperature dependence with a comparatively high activation energy. As the α-process involves liquid-like isotropic molecular reorientation, the slow process has to be attributed to vacancy diffusion, which modulates intermolecular dipole-dipole interactions, possibly accompanied by chair-chair interconversion of the cyclohexane ring. However, the low frequency relaxation features characteristic of vacancy diffusion cannot be detected due to experimental limitations.


Lack of beta 2-microglobulin on the surface of canine transmissible venereal tumor cells.
beta 2-Microglobulin (beta 2m) expression on the cell surface of the naturally occurring, allotransplantable canine transmissible venereal tumor (TVT) was investigated by use of indirect membrane immunofluorescence and radioimmunoassay. Two cell populations were identified in animal-derived, collagenase-disaggregated TVT cell suspensions. About 80% of the cells lacked surface beta 2m expression, whereas about 20% of the cells strongly reacted with anti-dog beta 2m serum. With the use of a cell separation technique, beta 2m-negative cells were demonstrated to carry TVT markers on their surface, whereas the beta 2m-positive cells did not express the tumor markers. The beta 2m-positive cells seemed, therefore, to be tumor-infiltrating host cells. These findings were supported by fluorescence staining studies of frozen sections of the TVT. The lack of beta 2m expression on the surface of TVT cells might explain the allotransplantability of this neoplasm, since beta 2m expression on the cell surface appeared to be obligatory for the expression of class I major histocompatibility complex antigens.


Psychometric evaluation of the Behavioral Activation for Depression Scale-Short Form in Alzheimer's caregivers.
The present study evaluated the psychometric properties of scores from the Behavioral Activation for Depression Scale Short Form (BADS-SF) in a sample of older age, spousal, Alzheimer's caregivers participating in an evaluation of Behavioral Activation (BA) therapy compared to an Information Support (IS) group. At baseline assessment, caregivers (N = 170) completed the BADS-SF, which is comprised of two subscales (Activation and Avoidance) that can be summed to produce a total score. Confirmatory factor analysis was used to evaluate structural validity. A two-factor solution fit the data adequately; however, the first item on the scale did not load onto either factor. Internal consistency reliability for the total and subscales scores was poor as measured by Cronbach's alpha. Construct validity was evidenced by significant expected relationships with depression. Pre- to post-intervention scores did not evidence sensitivity to change. These findings provide some support but raise important concerns about the validity and reliability of BADS-SF scores in a population of older adult caregivers.


Ataxia telangiectasia mutated deficiency does not result in genetic susceptibility to 50 Hz magnetic fields exposure in mouse embryonic fibroblasts.
Extremely low frequency magnetic field (ELF-MF) has been classified as a possible carcinogen to humans by the International Agency for Research on Cancer [2002]. However, debate on the genotoxic effects of ELF-MF has continued due to lack of sufficient experimental evidence. Ataxia telangiectasia mutated (ATM) plays a central role in DNA damage repair; its deficiency can result in cellular sensitivity to DNA-damaging agents. To evaluate the genotoxicity of ELF-MF, we investigated the effects of 50 Hz MF on DNA damage in ATM-proficient (Atm+/+ ) mouse embryonic fibroblasts (MEFs) and ATM-deficient (Atm-/- ) MEFs, a radiosensitive cell line. Results showed no significant difference in average number of γH2AX foci per cell (9.37 ± 0.44 vs. 9.08 ± 0.28, P = 0.58) or percentage of γH2AX foci positive cells (49.22 ± 1.86% vs. 49.74 ± 1.44%, P = 0.83) between sham and exposure groups when Atm+/+ MEFs were exposed to 50 Hz MF at 2.0 mT for 15 min. Extending exposure duration to 1 or 24 h did not significantly change γH2AX foci formation in Atm+/+ MEFs. Similarly, the exposure did not significantly affect γH2AX foci formation in Atm-/- MEFs. Furthermore, 50 Hz MF exposure also did not significantly influence DNA fragmentation, cell viability, or cell cycle progression in either cell types. In conclusion, exposure to 50 Hz MF did not induce significant DNA damage in either Atm+/+ or Atm-/- MEFs under the reported experimental conditions. Bioelectromagnetics. 39:476-484, 2018. © 2018 Wiley Periodicals, Inc.


Fulvestrant in advanced breast cancer: evidence to date and place in therapy.
Breast cancer is a classical hormone-dependent tumour; therefore, endocrine therapy is the mainstay of treatment for hormone receptor-positive, human epidermal growth factor 2-negative advanced breast cancer. Until recently, classical endocrine agents such as tamoxifen, steroidal and nonsteroidal aromatase inhibitors and fulvestrant have been widely used in postmenopausal patients to treat locally advanced or metastatic disease. However, for patients with this subtype of breast cancer, the landscape of endocrine therapy is rapidly changing. Therapies targeting oestrogen modulation have evolved in recent years following the introduction of targeted agents, mTOR and CDK 4/6 inhibitors that are administered in combination with hormone therapy. As a result, options for endocrine therapy have expanded in recent years, and a variety of single-agent or combinations of targeted drugs and endocrine therapies are accepted. Fulvestrant is a selective oestrogen receptor downregulator (SERD) which was introduced to clinical practice in 2002, initially with the indication to treat postmenopausal women with hormone-receptor-positive advanced breast cancer as second-line therapy postdisease progression after aromatase inhibitors or tamoxifen. Additionally, fulvestrant has also been shown to be active in patients previously untreated with endocrine therapy, either both in the neoadjuvant and the metastatic setting, alone or in combination with other targeted therapies. Currently, the standard dose is 500 mg, which is administered with a loading dose. Fulvestrant received a new FDA indication in December 2016, in combination with palbociclib, both in pre/peri/postmenopausal women with breast cancer progressing after endocrine therapy. This manuscript aims to give an overview of new efficacy data and the current role of fulvestrant in the systemic therapy of hormone-receptor-positive advanced breast cancer, in the context of other available therapeutic modalities.


HCV genetics and genotypes dictate future antiviral strategies.
At the end of the 1980s, the hepatitis C virus (HCV) was cloned and formally identified as the cause of the majority of non-A and non-B hepatitis cases. Today, around 170 million people worldwide are infected with HCV, making it five times more common than infection with the human immunodeficiency virus (HIV). Several methods exist which mediate the spread of infection. One of the most common and efficient is sharing or re-using injecting equipment; studies have indicated that 80-90% of individuals in some populations of intravenous drug users test positive in serum HCV assays. Contracting HCV from infected blood transfusions was also a major cause of infection before screening tests were introduced in the early 1990s. Other possible, but less common, methods of infection transmission include mother-to-child during pregnancy, sexual contact and nosocomial acquisition (for example between surgical or dialysis patients). It appears that concurrent HIV-1 infection increases the risk of HCV transmission via the mother-to-child or sexual routes.


A manual system for patients' accounting records.
A medical practitioner's formalised education and practical training prior to private practice does not usually include methodology in keeping patients' accounting records. This article is directed at assisting practitioners to implement a suitable system, as well as to provide standards against which they can assess their current procedures.


Accuracy of abnormal paraspinal muscle findings on contrast-enhanced MR images as indirect signs of unilateral cervical root-avulsion injury.
To evaluate the accuracy of abnormal magnetic resonance (MR) findings in the paraspinal muscles as indirect signs of nerve-root avulsion injury. Forty-three consecutive patients suspected of having unilateral root-avulsion injury underwent MR imaging and were evaluated. Paraspinal muscles were evaluated for abnormal signal intensity on T1- and T2-weighted images, abnormal enhancement on images obtained after contrast material enhancement, and muscle volume loss. MR images were interpreted independently by two observers for interobserver variability. MR findings were compared with findings of root continuity, determined with a combination of surgery and clinical evaluation. Sensitivities, specificities, and kappa values of the findings were calculated. Sensitivities of MR findings in the paraspinal muscles indicating root-avulsion injury were 88% (36 of 41 patients) for abnormal enhancement, 83% (34 of 41 patients) for high signal intensity on T2-weighted images, 37% (15 of 41 patients) for high signal intensity on T1-weighted images, and 71% (29 of 41 patients) for muscle volume loss. Specificities for all findings were 100% (two of two patients). Of the paraspinal muscles, findings in the multifidus muscle were the most accurate and provided the highest interobserver agreement (kappa = 0.81). Contrast material-enhanced abnormal MR findings in the paraspinal muscles are accurate in indicating root-avulsion injuries, and abnormal enhancement in the multifidus muscle is the most accurate among paraspinal muscle findings.


Two Cases of Influenza B Virus-Related Fatal Fulminant Pneumonia Complicated With Staphylococcus aureus Infection in China Diagnosed Using Next-Generation Sequencing (2018).
Two rare cases of Chinese female patients with influenza B virus infection complicated with both fulminant pneumonia and septicemia caused by Panton-Valentine leukocidin(PVL) positive methicillin-sensitive Staphylococcus aureus (MASS) were reported for the first time in China through next-generation sequencing (NGS). An increasing body of evidence indicates that co-infection with influenza B virus and bacterial pneumonia is often fatal. Rapid and precise identification of the co-infection bacteria can guide the selection of treatment for patients with influenza virus infection in the clinical setting. In this study, next-generation sequencing (NGS) was applied for the rapid diagnosis of these two cases. Despite the unfavorable survival outcome of these patients, the application of next-generation sequencing showed promise as a diagnostic tool for the rapid diagnosis of unknown pathogens in patients with bacterial pneumonia and sepsis. This method can guide the administration of medications in such patients.


[Hans von Haberer--the beginnings of reconstructive carotid surgery].
Hans von Haberer (1875-1958) gained wide experience in the reconstructive surgery of vascular aneurysms at the universities of Innsbruck, Graz, Düsseldorf and Cologne. In this period he operated on 421 vascular aneurysms--including 30 carotid aneurysms--mainly by means of direct circular vascular suture. In 1914 von Haberer described the first repair of a carotid aneurysm. Therefore he is the pioneer of reconstructive carotid surgery. Based on detailed clinical and operation reports on approximately 16,000 cases, written by Hans von Haberer between 1904 and 1949, and on the contemporary literature, we describe his experience in vascular surgery.


Expression of HRF20, a regulatory molecule of complement activation, on peripheral blood mononuclear cells.
HRF20 is a homologous restriction factor of 20,000 MW that prevents cells from membrane attack by homologous complement. HRF20 has been identified by a monoclonal antibody (mAb), 1F5, and is one of the phosphatidylinositol(PI)-anchored cell-surface glycoproteins. We analysed the distribution of HRF20 expressed on subsets of peripheral blood lymphocytes using 1F5. HRF20 is expressed in relatively large amounts on T cells. In contrast, adherent cells possess smaller amounts of HRF20 while having large quantities of decay-accelerating factor (DAF). Although DAF was shown to be deficient or present at rather low levels on NK cells, HRF20 was detected in 95% of large granular lymphocytes (LGL), as described by FACS analysis. We also determined the effect of 1F5 on both mononuclear leucocytes and T cells in terms of their growth response. The results show that 1F5 induces T-cell proliferation when cells are stimulated with interleukin-2 (IL-2). In addition, induction of proliferation is facilitated by cross-linking 1F5 with a second antibody. These results suggest that HRF20 expressed on T cells not only protects them from cytotoxic attack by homologous complement, but also may initiate intracellular signals leading to cell activation when they happen to be cross-linked.


Machine learning-enabled discovery and design of membrane-active peptides.
Antimicrobial peptides are a class of membrane-active peptides that form a critical component of innate host immunity and possess a diversity of sequence and structure. Machine learning approaches have been profitably employed to efficiently screen sequence space and guide experiment towards promising candidates with high putative activity. In this mini-review, we provide an introduction to antimicrobial peptides and summarize recent advances in machine learning-enabled antimicrobial peptide discovery and design with a focus on a recent work Lee et al. Proc. Natl. Acad. Sci. USA 2016;113(48):13588-13593. This study reports the development of a support vector machine classifier to aid in the design of membrane active peptides. We use this model to discover membrane activity as a multiplexed function in diverse peptide families and provide interpretable understanding of the physicochemical properties and mechanisms governing membrane activity. Experimental validation of the classifier reveals it to have learned membrane activity as a unifying signature of antimicrobial peptides with diverse modes of action. Some of the discriminating rules by which it performs classification are in line with existing "human learned" understanding, but it also unveils new previously unknown determinants and multidimensional couplings governing membrane activity. Integrating machine learning with targeted experimentation can guide both antimicrobial peptide discovery and design and new understanding of the properties and mechanisms underpinning their modes of action.


Mucosal iron retention and plasma iron absorption in the duodenum and jejunum of dogs.
Two groups of non-anemic dogs, one with normal tissue iron stores and one with decreased tissue iron stores, underwent a surgical construction of two equal segments of duodenum and jejunum. A solution of 0.1 mg ferrous sulfate and 1 mg ascorbic acid was injected into the lumen of each segment. The solution for the duodenal segment contained 30 muc of iron59, for the jejunum segment 60 muc of iron55. The solutions were left in the segments for 2 1/2 hours before washout. On the 14th postoperative day, iron59 and iron55 radioactivity per ml/RBC was measured, and iron uptake by segments determined in two ways. Bone marrow, liver, and spleen were histologically assessed of iron stores. In dogs with normal iron stores, percent iron retained was slightly higher in jejunum that duodenum. In dogs with decreased iron stores percent retention was always higher in duodenum; in this group iron retained was about four times higher than in dogs with normal iron stores. This indicates that mucosal uptake of iron from lumen and mucosal transfer of iron from plasma vary inversely with body iron stores, but compared to mucosal uptake, mucosal transfer is more restricted to duodenum, more affected by body iron stores, more limited, and more crucial to regulation of iron absorption.


Restricted Kinematically Aligned Total Knee Arthroplasty Following Failed Oxford Unicompartmental Knee Arthroplasty.
In this report, we describe how to revise a failed Oxford unicompartmental knee arthroplasty to kinematically aligned total knee arthroplasty (TKA). Its benefits are the maintenance of the native joint line along with the avoidance of supplemental parts, such as metal augments and stems. This can be applied to patients whose medial tibial cortex is well preserved. The distal cutting plane and rotation alignment are decided before the removal of the femoral component. The tibial cutting plane is up to 12 mm below the lateral joint surface and the varus is up to 5° below the extramedullary rod. Eventually, the native joint line and alignment along with the soft tissue envelope can be well maintained, similar to the restricted kinematically aligned TKA.


Dacin, one metalloproteinase from Deinagkistrodon acutus venom inhibiting contraction of mouse ileum muscle.
Mice were bitten by five-pace vipers (Deinagkistrodon acutus), and then envenomed. It was well-known that the snake venom mainly disturbed the blood homeostasis of the envenomed victims. Ocassionally, we found that the venom of D. acutus could inhibit the contraction tension of mouse ileum, so in this study we aimed to identify the active component inhibiting the contraction tension of mouse ileum in the snake venom. The active component inhibiting the contraction tension of mouse ileum, designated as Dacin, was isolated from D. acutus venom, purified to protein homogeneity and composed of a single peptide chain, about 23 kDa analyzed by SDS-PAGE, and 22, 947. 9 Da measured by MALDI-TOF-MS. Not only the results of its PMF blasted by Mascot indicated that Dacin may be one snake venom metalloproteinase (SVMP), but also the results of the biochemical and in-vivo assays as follow demonstrated that it was one SVMP: it cleaved Aα and Bβ chains, not Cγ of bovine fibrinogen within 1 h, and also hydrolyzed fibrin polymer; besides its fibrino(geno)lytic activities were strongly inhibited by β- mercaptoethanol, EDTA and EGTA; and it could induce a hemorrhagic reaction under the dorsal skin of mouse. In the isolated tissue assays, Dacin caused the concentration-dependent and time-dependent inhibitory actions on the spontaneous contraction tension of the ileum smooth muscle of mouse, and the inhibitory effects were irreversible. Taken together, for the first time one active component (Dacin, a SVMP) that irreversibly inhibited the spontaneous contraction tension of mouse ileum has been isolated and identified from D. acutus venom. The findings may provide not only a new insight for toxicological researches on SVMPs and venoms of the vipers, but also a reference for clinicians to treat the snake-bitten victims. However, Dacin's inhibitory molecular mechanism will be further studied in the future.


Ethno-botanical studies from Northern Pakistan.
In this research paper efforts have been made to document the ethno-botanical knowledge of important plant species found in Northern Pakistan. It includes Thandiani, Galiat, Kaghan, Swat, Buner, Dir, Chitral and Northern Areas of Pakistan. The area has many climatic and vegetation zones or biomes. Locals residing in mountainous areas belonging to various ethnic groups are traditionally utilizing plants over many generations; these ethnic groups have their distinct life style, belief, traditions and cultural heritage. Plant collection and data regarding traditional uses in various areas of Northern Pakistan has been done periodically in different flowering /fruiting seasons. Locals of old age belonging to various ethnic groups were personally interviewed for establishing uses of plants. Photography is done for easy identification and habitat recognition. Collected plant specimens and seeds were preserved. Plant species were dried, mounted, identified and authenticated. 135 genera belonging from 66 families of angiosperms and gymnosperms were studied and described.76 species were known to have traditional and ethno botanical uses. Plants have been utilized for many generations. Ethnic groups have distinct life style and have different economic uses for these plants. Due to unsustainable exploitation of natural habitats scarcity of drug plants has occurred. As consequence some species are depleting and may become extinct in near future, e.g. Morchella esculenta, Colchicum lueteum and Viola serpens are just a few of these. Although some sporadic information is available about the flora of this region but very little documented record of the ethno-botanically important plants has been established. It is expected that this research paper will be beneficial for students, researchers, farmers, foresters and general public. On the basis of data obtained it is concluded that ethno-botanical Flora of Northern Pakistan is quite rich and is diverse, due to the difference in altitude, climate and other topographic conditions.


Brow lift via the direct and trans-blepharoplasty approaches.
Brow ptosis occurs as part of the aging process, and as a complication of facial nerve paresis. The article addresses the options available for correction of brow ptosis. The direct brow lift is effective for medial and central brow ptosis, and additional lift laterally may occasionally be needed. This is achieved with either a temporal external lift or an internal lift combined with blepharoplasty. The direct brow lift is suitable for any degree and pattern of brow ptosis, usually in males. It is also suitable for older females as well as male patients with facial paresis or marked involutional brow ptosis. The trans-blepharoplasty brow lift is suitable for relatively small degrees of brow ptosis affecting mainly the lateral two-thirds of the brow in any age group. It is often combined with upper lid blepharoplasty and is performed through the same incision. Complications associated with the direct brow lift include a cosmetically disturbing scar, granuloma formation due to the use of braided absorbable sutures rather than monofilament sutures, and the brow descending again. There may be temporary patches of reduced sensation in the forehead which normally recover in a few months. Complications associated with the trans-blepharoplasty brow lift include less lift than desired, and sutures causing dimpling of the skin. These two techniques are useful additions to the approaches for patients with brow ptosis.


Basic study of a new denture base resin applying hydrophobic methacrylate monomer.
To improve the water sorption of poly(methyl methacrylate), new hydrophobic monomers, such as norbonyl and phenyl methacrylate, were studied to determine the resin with lower water sorption with no decrease in mechanical property. Water sorption of the copolymers of the hydrophobic monomers and MMA decreased with the increase in the concentration of the monomers. Compressive and bending strength of the copolymers were higher than that of PMMA, and the elastic modulus in bending was the same as that of PMMA. In addition, the transverse-deflection values satisfied ADA specifications. Dynamic mechanical thermal analysis of the copolymers showed a similar tendency to that of PMMA in spite of the introduction of bulky groups, such as norbonyl and phenyl, in the polymer molecule. The polymerization shrinkage in volume was in the following order: norbonyl < phenyl < methyl methacrylate.


Initial Clinical Outcomes of Percutaneous Full-Endoscopic Lumbar Discectomy Using an Interlaminar Approach at the L4-L5.
Percutaneous full-endoscopic discectomy (PED) is being increasingly used because of its potential to minimalize soft-tissue damage and decrease hospital stay. PED using the interlaminar approach (PED-IL) at L4-L5 is performed by only a few surgeons. To the best of our knowledge, the safety and efficacy of PED-IL at L4-L5, without experience in PED via a transforaminal approach (PED-TF) has not been previously reported. This study aimed to evaluate initial clinical outcomes and complications of PED-IL at L4-L5 without experience in PED-TF. Retrospective evaluation. An urban minimally invasive spine hospital. Of a total of 50 patients (36 men and 14 women, ages ranging from 21-59 years, with the average age being 40.3 years old), 16 cases were performed at L4-L5 and 34 cases were performed at L5-S1. PED-IL was successfully completed in all cases, and no case required conversion to open surgery. The operative time, hospital stay, modified MacNab criteria, and visual analog scale (VAS) scores were examined at L5-S1 (range: 41-112). There was no significant difference in operative time between the L4-L5 and L5-S1 groups; the operative time was gradually decreased. The mean hospital stay was 2.9 days (range: 2-8 days). According to modified MacNab criteria, 20 cases (6 at L4-L5 and 14 at L5-S1) were excellent, 27 (10 at L4-L5 and 17 at L5-S1) were good, one at L5-S1 was fair, and 2 at L5-S1 were poor. Two perineurium tears occurred at L5-S1. There was no infection or recurrence of herniated nucleus pulposus (HNP). The clinical outcomes of PED-IL at L4-L5 were equal to those at L5- S1. The mean operative time was 71.3 ± 19.3 minutes for all cases (range: 41-112 mins.),76.1 ± 16.8 minutes at L4-L5 (range: 52-102 mins.), and 70.5 ± 20.1 minutes at L5-S1 (range: 41-112 mins.). A small sample size and a short follow-up period. The clinical outcomes of PED-IL at L4-L5 were equal to those at L5-S1. Therefore, PED-IL is suitable to be a standard method for any type of intracanalicular disc herniation.


Does Preoperative Weight Change Predict Postoperative Weight Loss After Laparoscopic Sleeve Gastrectomy?
Background: Some institutions and insurance companies mandate a preoperative weight loss regimen prior to bariatric surgery. Previous studies suggest little to no correlation between preoperative and postoperative weight loss for laparoscopic Roux-en-Y gastric bypass (RNYGB). This study examined the impact of preoperative weight change for patients undergoing laparoscopic sleeve gastrectomy (LSG). Materials and Methods: A retrospective analysis was performed on patients undergoing LSG at the authors' institution from 2010 to 2012. Patients were grouped based on preoperative weight gain or loss. The correlation between preoperative BMI change and postoperative BMI change was studied, as well as length of surgery. Results: Of 141 patients with 1-year follow-up, 72 lost, six maintained, and 64 gained weight preoperatively. Percentage of excess BMI loss at 1 year was not statistically different between those who lost weight and those who gained weight. Percent change in BMI from initial visit to surgery does not correlate with change in BMI at 1 year postoperatively or with length of surgery. Conclusions: Preoperative weight loss is not a reliable predictor of postoperative weight loss or shorter operative time after LSG. Potential patients who otherwise meet indications for LSG should not be denied based on inability to lose weight.


Erroneous neuraxial administration of neuromuscular blocking drugs: Clinical and human factors analysis.
Drug errors during neuraxial anaesthesia or analgesia are not well known. To review the clinical consequences associated with incorrect administration of neuromuscular blocking drugs (NMBDs) during spinal or epidural anaesthesia, and to investigate human factors and strategies available to help prevent such errors. A review of reports of neuraxial administration of NMBDs in humans. Published reports of errors involving NMBDs. We searched the period between 1965 and 2019. Error reports in any language. Nonneuraxial drug errors were excluded. We identified 20 reports involving seven different NMBDs inadvertently administered via the epidural or intrathecal routes. All patients developed systemic neuromuscular junction blockade. Fourteen errors occurred while patients were awake. The onset of action was delayed following epidural rocuronium and suxamethonium. The duration of action was prolonged following epidural administration of vecuronium, pancuronium, cisatracrium and suxamethonium. Five patients required emergency airway interventions. Intrethecal gallamine caused convulsions and muscle spasms migrating up the body. Syringe swap was the primary cause for the majority of errors and perceptual errors were the most common. Implementation of recommendations could have prevented the errors. Following the epidural injection of NMBDs the effects are delayed and prolonged. There was no serious morbidity reported following neuraxial administration of the NMBDs used in current practice. Perceptual errors resulting in incorrect syringe choice were the commonest cause. Four measures can be introduced to reduce such errors.


Malnutrition of children in developing countries: what can we do?
This informal paper is a personal account of the development of my work on malnourished children, starting with clinical studies in Jamaica and the challenge of an unacceptably high mortality rate; moving on to the problem of how to define less severe malnutrition in the community; and ending with some reflections on the enormously difficult question of prevention and the contribution that richer countries such as the UK could make.