Platinum (II) Compounds With Antitumor Activity Studied by Molecular Mechanics.
A SERIES OF PT(LL) COMPLEXES WITH ANTITUMOR PROPERTIES: [1,2-bis(2,6-dichloro-4-hydroxyphenyl)ethylenediamine]PtL(2) (meso-1-PtL(2)) and [erythro-1-(2,6-dichloro-4-hydroxyphenyl)-2-(2-halo-4-hydroxyphenyl)ethylenediamine]PtL(2), [2L=2Cl-,2I-,SO(4) (2)-; halo = F (erythro-8-PtL(2)),halo = Cl (erythro-9-PtL(2))] has been modelled by molecular mechanics (MM). The MM calculations were carried out for different isomers and ligand conformations meso-delta, meso-lambda, d,l-delta, d,I-lambda. The compounds with the lowest MM energies have the same geometries as those obtained by X-ray analysis. The calculated MMX energy orders: meso-1-PtL(2) < erythro-9-PtL(2) < erythro-8-PtL(2) for L=I-, Cl- and SO(4) (2-) are reverse to the known antitumor activity order - the lowest energy complex (the most stable one)is the one with the highest estrogen activity (meso-1-PtL(2)). The type of the leaving group (L) does not alter the energy order, which is in agreement with the biological experiments that show a slight dependence of the estrogen properties on the leaving group type.


The determination of enantiomeric excess of valine by ODESSA solid-state NMR experiment.
The enantiomeric excess (ee) can be determined by many methods; one among them is nuclear magnetic resonance in solid-state (SS NMR). In this study we used the SS NMR ODESSA experiment for determination of the ee of valine.


Unveiling nature's potential weapon: Magnolol's role in combating bladder cancer by upregulating the miR-124 and inactivating PKC-δ/ERK axis.
Bladder cancer (BC) is a challenging disease to manage. Researchers have been investigating the potential of magnolol, a compound derived from Magnolia officinalis, as an anti-cancer agent. However, the exact regulatory mechanism of magnolol and its impact on the NF-κB signaling pathway in BC remain unclear. To comprehensively evaluate its therapeutic potential, the researchers conducted a series of experiments using BC cell lines (TSGH8301, T24, and MB49) and in vivo animal models. The results of the study demonstrated that magnolol exhibits cytotoxic effects on BC cells by activating both the extrinsic and intrinsic apoptosis signaling pathways. Additionally, the expression of anti-apoptotic genes was downregulated by magnolol treatment. The researchers also uncovered the regulatory role of PKCδ/ERK and miR-124-3p in the NF-κB pathway, which may be influenced by magnolol. Treatment with magnolol led to the inactivation of PKCδ/ERK and an increase in miR-124-3p expression, effectively inhibiting NF-κB-mediated progression of BC. Importantly, the administration of magnolol did not result in significant toxicity in normal tissues, highlighting its potential as a safe adjunctive therapy with minimal adverse effects. These findings position magnolol as a promising therapeutic agent for the treatment of BC. By activating apoptosis signaling pathways and inhibiting NF-κB pathway through the upregulation of miR-124-3p and downregulation of PKCδ/ERK activation, magnolol holds promise for suppressing tumor progression and improving patient outcomes in BC. Further research and clinical trials are warranted to explore the full potential of magnolol in the future.


Interventions to Promote End-of-Life Conversations: A Systematic Review and Meta-Analysis.
Although several interventions aimed to promote end-of-life conversations are available, it is unclear whether and how these affect delivery of end-of-life conversations. Measuring the processes associated with high-quality end-of-life care may trigger improvement. To estimate the effect of interventions aimed to promote end-of-life conversations in clinical encounters with patients with advanced chronic or terminal illness or their family, on process indicators of end-of-life conversations. Systematic review with meta-analysis (PROSPERO no. CRD42021289471). Four databases (PubMed, CINAHL, PsycINFO, and Scopus) were searched up to September 30, 2021. The primary outcomes were any process indicators of end-of-life conversations. Results of pairwise meta-analyses were presented as Risk Ratio (RR) for occurrence, standardized mean difference (SMD) for quality and ratio of means (ROM) for duration. Meta-analysis was not performed when fewer than four studies were available. A total of 4,663 articles were scanned. Eighteen studies were included in the systematic review and 16 entered at least one meta-analysis: documented occurrence (n = 8), patient-reported occurrence (n = 4), patient-reported-quality (n = 4), duration (n = 4). There was significant variability in settings, patients' clinical conditions, and professionals. No significant effect of interventions on documented occurrence (RR 1.54, 95% CI 0.84-2.84; I2 91%), patient-reported occurrence (RR 1.52, 95% CI 0.80-2.91; I2 95%), patient-reported quality (SMD 0.83, 95% CI -1.06 to 2.71; I2 99%), or duration (ROM 1.20, 95% CI 0.95-1.51; I2 65%) of end-of-life conversations was found. Data on frequency were conflicting. Interventions targeting multiple stakeholders promoted earlier and more comprehensive conversations. Heterogeneity was considerable, but findings suggest no significant effect of interventions on occurrence, patient-reported quality and duration of end-of-life conversations. Nevertheless, we found indications for interventions targeting multiple stakeholders to promote earlier and more comprehensive conversations.


ACL Injury Prevention Training Results in Modification of Hip and Knee Mechanics During a Drop-Landing Task.
Injury prevention training has been shown to be effective in reducing the incidence of noncontact anterior cruciate ligament (ACL) injury; however, the underlying reason for the success of these training programs is unclear. To investigate whether an ACL injury prevention program that has been shown to reduce the incidence of ACL injury alters sagittal plane hip and knee biomechanics during a drop-landing task. Descriptive laboratory study. Thirty female club soccer players (age range, 11-17 years) with no history of knee injury participated in this study. Kinematics and ground-reaction forces were collected while each participant performed a drop-landing task prior to and immediately after participation in a 12-week ACL injury prevention training program. After ACL injury prevention training, participants demonstrated decreased knee extensor moments (P = .03), increased energy absorption at the hip (P = .04), decreased knee-to-hip extensor moment ratios (P = .05), and decreased knee-to-hip energy absorption ratios (P = .03). Participation in an ACL injury prevention training program decreased reliance on the knee extensor muscles and improved use of the hip extensor muscles, which may explain the protective effect of this type of training program on ACL injury. Based on these findings, clinicians can better understand how ACL injury prevention training, such as the Prevent Injury and Enhance Performance (PEP) Program, may change movement behavior at both the hip and knee. Furthermore, the study findings may support the implementation of the PEP Program, or a similar program, for clinicians aiming to improve use of the hip in an effort to reduce knee loading and consequent injuries.


Profiles and Transitions of Loneliness and Depressive Symptoms among Migrant Children: Predictive Role of Bullying Victimization.
Although loneliness and depressive symptoms are particularly prominent among migrant children and often occur simultaneously, little is known about the co-occurring and transitional nature of loneliness and depressive symptoms among migrant children, and the role of bullying victimization on their profiles and transitions. This study examined the profiles and transitions of loneliness and depressive symptoms among migrant children using latent profile analysis and latent transition analysis, as well as how bullying victimization predicted their profile memberships and transitions. A total of 692 migrant children (55.3% males, Mage = 9.41, SD = 0.55, range = 8 to 12 years old at T1) participated in both two waves of the study over six months. The results indicated that low profile (59.2%), moderate profile (22.0%), moderately high profile (14.3%), and high profile (4.5%) were identified at Time 1; low profile (69.4%), predominantly loneliness profile (16.8%), predominantly depressive symptoms profile (6.5%), and high profile (7.3%) were identified at Time 2. Migrant children in at-risk profiles displayed varying degrees of transition. Migrant children experiencing more bullying victimization were more likely to belong or transition to at-risk profiles. The findings highlight the importance of subgroup differences considerations in understanding the co-occurring and transitional nature of loneliness and depressive symptoms, as well as the predictive role of bullying victimization, informing effective strategies for prevention and intervention.


Interactions between quadruple-stranded oligodeoxyribonucleotides and drugs.
Circular dichroism (CD) and fluorescence spectra have been measured for complexes formed between four-stranded G4-DNA and ethidium bromide (EB). The EB-G4-DNA complexes showed similar induced CD spectra, compared with the induced CD spectrum of the EB-calf thymus DNA complex.


Heat production as a quantitative parameter of phagocytosis.
Microcalorimetry was applied to measure phagocytosis by human peripheral blood neutrophils and monocytes. Heat production was 9.1 +/- 2.6 microW by 1 X 10(6) unstimulated neutrophils and increased to 28.4 +/- 3.2 microW in association with phagocytosis. The increase in heat production was directly proportional to the number of Saccharomyces cerevisiae particles phagocytosed as well as to the concentration of opsonizing serum. No heat increase was observed in the absence of phagocytosis. An increase in heat production by monocytes was also observed in association with phagocytosis, but it was much less obvious than that by neutrophils. Heat production can thus be used as a quantitative measure of phagocytosis.


Synthesis of a new biological response modifier thyrnosin beta(4) analogue and its restorative effect on depressed.
Thymosin beta(4) is a polypeptide isolated from thymosin fraction 5. This peptide exhibits important activities in the regulation and differentiation of thymus-dependent lymphocytes. An analogue of thymosin beta(4), [Phe(4F)(12)] deacetyl- thymosin beta(4), was synthesized by a solution method, followed by deprotection with 1 M trifluoromethanesulphonic acid (TFMSA)-thioanisole (molar ratio, 1:1) in trifluoroacetic acid (TFA) in the presence of dimethlselenium. Finally, the deprotected peptide was incubated with dithiothreitol to reduce sulphoxide on the methionine side chain. The synthetic [Phe(4F)(12)]deacetyl-thymosin beta(4) was found to have a restoring effect on the impaired blastogenic response of T-lymphocytes isolated from uraemic patients with recurrent infectious diseases. This analogue exhibited stronger restorative activity than that of our synthetic deacetyl-thymosin beta(4).


Implementing the Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis: Long-term effect of a simple educational intervention.
A standardized pathology management tool for melanocytic skin lesions may improve patient care by simplifying interpretation and categorization of the diverse terminology currently extant. To assess an online educational intervention that teaches dermatopathologists to use the Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis (MPATH-Dx), a schema collapsing multiple diagnostic terms into 5 classes ranging from benign to invasive melanoma. Practicing dermatopathologists (N = 149) from 40 US states participated in a 2-year educational intervention study (71% response rate). The intervention involved a brief tutorial followed by practice on 28 melanocytic lesions, with the goal of teaching pathologists how to correctly use the MPATH-Dx schema; competence using the MPATH-Dx tool 12-24 months postintervention was assessed. Participants' self-reported confidence using the MPATH-Dx tool was assessed preintervention and postintervention. At preintervention, confidence using the MPATH-Dx tool was already high, despite 68% lacking prior familiarity with it, and confidence increased postintervention (P = .0003). During the intervention, participants used the MPATH-Dx tool correctly for 90% of their interpretations; postintervention, participants used the MPATH-Dx tool correctly for 88% of their interpretations. Future research should examine implementing a standardized pathology assessment schema in actual clinical practice. Dermatopathologists can be taught to confidently and competently use the MPATH-Dx schema with a simple educational tutorial followed by practice.


Availability and effects of n-TiO2 and PCB77 in fish in vitro models of the intestinal barrier and liver under single- and/or co-exposure scenarios.
Titanium dioxide nanoparticles (n-TiO2) and polychlorinated biphenyls (PCBs) can be present in the food of fish, leading to intestinal exposure uptake, and accumulation in inner organs. This study examined combination effects of n-TiO2 and PCB77 in vitro models of the fish intestinal epithelium and liver, i.e., RTgut-GC cell cultures grown in ThinCerts™ and RTL-W1 cell cultures grown in standard tissue culture plates. Mass spectrometry and microscopy techniques were used to obtain information on nanoparticle translocation across the intestinal barrier model. In addition, the substances' effect on intestinal barrier permeability, cell viability, expression of dioxin - and antioxidant response element -controlled genes, and induction of cytochrome P450 1a (Cyp1a)-dependent ethoxyresorufin-O-deethylase (EROD) activity were assessed. TiO2 nanoparticles were taken up by RTgut-GC cells and detected in the bottom compartment of the intestinal epithelial barrier model. It was not possible to conclude definitively if n-TiO2 translocation occurred via transcytosis or paracellular migration but observations of nanoparticles in the lateral space between adjacent epithelial cells were rare. PCB77 (1 and 10 µM, 24 h) did not affect barrier permeability, i.e., n-TiO2 translocation is probably not facilitated in case of co-exposure. Furthermore, previous and simultaneous exposure to n-TiO2 (1 and 10 mg/L, 24 h) did not have any influence on PCB77-induced Cyp1a mRNA and enzyme activity levels in RTL-W1 cells. Furthermore, there were no significant differences in expression of antioxidant response element-controlled genes comparing control, single substance, and mixture treatments, not even following long-term exposure (0.01-1 mg/L n-TiO2 + 1 nM PCB77, 4 weeks). While an underestimation of the effects of n-TiO2 and PCB77 cannot be fully excluded as concentration losses due to sorption to cell culture plastics were not measured, the results suggest that the test substances probably have a low potential to exhibit combination effects on the assessed endpoints when co-existing in fish tissues.


Parenting Style Frequency and Their Sociodemographic Determinants in Buraidah City, Qassim, Saudi Arabia.
Background Three parenting styles still form the foundation for today's research into childhood development. The natural mode of parenting falls somewhere among Baumrind's parenting styles (authoritative, authoritarian, and permissive). Due to the lack of research that integrates the relationship between parenting styles and socioeconomic status in Saudi Arabia, we decided to study different types of parenting styles and their relationship with sociodemographic status. Objective This study aimed to estimate the frequency of parenting styles among adolescent children's parents in Buraidah City, Qassim, during the year 2021. Methods A descriptive cross-sectional community-based study was conducted among 496 parents. A structured questionnaire was used to collect data. The Parenting Style Dimension Questionnaire (PSDQ) was used to identify the parenting style of each participant. Data were analyzed using the Epi Info software version 7.2.5 (Centers for Disease Control and Prevention, Atlanta, GA, USA). Results Among the surveyed parents, there were 250 (50.4%) males, and the mean age was 36.7 (±10.6) years. The majority (390, 78.6%) live in a nuclear family with a family size ranging from four to six members (285, 57.5%). A total of 451 (90.9%) parents were educated in secondary school and above. In this study, the common parenting style was the authoritative style (380, 76.6%). The two sociodemographic factors found to be statistically correlated with authoritative style were big family size (P=0.014) and the husband's income (P=0.012). Conclusion The study revealed that the authoritative parenting style was the dominant type among younger parents. However, no factors affect the parents' style except family size and the husband's income. It is important to develop parenting education programs to provide parents with the necessary skills and abilities to deal with their children.


Computational studies of the principle of dynamic-change-driven protein interactions.
Dynamic allostery emphasizes a role of entropy change manifested as a sole change in protein fluctuations without structural changes. This kind of entropy-driven effect remains largely understudied. The most significant examples involve protein-ligand interactions, leaving protein-protein interactions, which are critical in signaling and other cellular events, largely unexplored. Here we study an example of how protein-protein interaction (binding of Ras to the Ras binding domain [RBD] of the effector protein Raf) affects a subsequent protein association process (Ras dimerization) by quenching Ras internal motions through dynamic allostery. We also investigate the influence of point mutations or ambient temperature, respectively, on the protein dynamics and interaction of two other systems: in adenylate kinase (ADK) and in the EphA2 SAM:Ship2 SAM complex. Based on these examples, we postulate that there are different ways in which dynamic-change-driven protein interactions are manifested and that it is likely a general biological phenomenon.


1978 memorial award paper: a computer-aided technique for overlaying cerebral angiograms onto computed tomograms.
We have developed a method which uses a digital computer to combine angiographic images of the cerebral vasculature with a computed tomogram of the brain. The procedure is simple and could be implemented in any radiology department equipped with both a CT scanner and a bi-plane angiography suite. We have performed the entire process in prototype on phantoms and on a patient and have produced images that appear accurate and informative.


Emerging Insights Into the Role of the Hippo Pathway in Multiple Myeloma and Associated Bone Disease.
Multiple myeloma (MM) is an incurable plasma-cell dyscrasia with numerous treatment options currently available; however, drug resistance is usually inevitable, so there is a constant need for novel treatment approaches. The Hippo pathway has emerged as an important mediator of oncogenesis in solid tumors. More recently, its key role in regulating apoptosis and mediating resistance in MM and other hematologic malignancies has been demonstrated in preclinical studies, which provides a strong basis for further clinical investigation. The Hippo pathway is also implicated in the pathogenesis of MM-induced bone disease, as it regulates both osteoblast and osteoclast function. We provide an overview of the available data regarding the role of the Hippo signaling components in the pathophysiology of MM. A better understanding of the underlying interactions at the molecular and cellular levels will lead to novel and promising treatment approaches.


Greater local diversity under older species pools may arise from enhanced competitive equivalence.
Ecological communities typically contain more species when located within geologically older regions. This pattern is traditionally attributed to the long-term accumulation of species in the regional species pool, with local species interactions playing a minor role. We provide evidence suggesting a more important role of local species interactions than generally assumed. We assembled 320 communities of root-associated fungi under 80 species pools, varying species pool richness and the mean age of the sites from which the fungi were collected across a 4-myr soil chronosequence. We found that local diversity increased more with increasing species pool richness when species were from older sites. We also found that older species pools had lower functional and phylogenetic diversity, indicating greater competitive equivalence among species. Our results suggest that older regions have higher local richness not simply because older pools are more speciose but also because species have evolved traits that allow them to locally co-occur.


Endocrine responses in long-duration manned space flight.
The bioassay of body fluids experiment is designed to evaluate the biochemical adaptation resulting from extended exposure to space flight environment by identifying changes in hormonal and associated fluid and electrolyte parameters reflected in the blood and urine of the participating crewmen. The combined stresses of space flight include weightlessness, acceleration, confinement, restraint, long-term maintenance of high levels of performance, and possible desynchronosis. Endocrine measurements to assess the physiological cost of these stresses have been considered from two aspects. Fluid and electrolyte balance have been correlated with weight loss, changes in the excretion of aldosterone and vasopressin and fluid compartments. The second area involves the estimation of the physiological cost of maintaining a given level of performance during space flight by analysis of urinary catecholamines and cortisol. Inter-individual variability was demonstrated in most experimental indices measured; however, constant patterns have emerged which include: body weight change; increases in plasma renin activity; elevations in urinary catecholamines, ADH, aldosterone and cortisol concentrations. Plasma cortisol decreases in immediate postflight samples with subsequent increase in 24-hour urines. The measured changes are consistent with the prediction that a relative increase in thoracic blood volume upon transition to the zero-gravity environment is interpreted as a true volume expansion resulting in an osmotic diuresis. This diuresis in association with other factors ultimately results in a reduction in intravascular volume, leading to an increase in renin and a secondary aldosteronism. Once these compensatory mechanisms are effective in reestablishing positive water balance, the crewmen are considered to be essentially adapted to the null-gravity environment. Although the physiological cost of this adaptation must reflect the electrolyte deficit and perhaps other factors, it is assumed that the compensated state is adequate for the demands of the environment; however, this new homeostatic set is not believed to be without physiological cost and could, except with proper precautions, reduce the functional reserve of exposed individuals.


Do differences in brain activation challenge universal theories of dyslexia?
It has been commonly agreed that developmental dyslexia in different languages has a common biological origin: a dysfunction of left posterior temporal brain regions dealing with phonological processes. Siok, Perfetti, Jin, and Tan (2004, Nature, 431, 71-76) challenge this biological unity theory of dyslexia: Chinese dyslexics show no deficits in posterior temporal brain regions but a functional disruption of the left middle frontal gyrus. Here, I will argue that these data do not challenge universal cognitive theories of dyslexia according to which weaknesses in the ability to process the phonological features of language are at the origin of dyslexia.


Correspondence of the functional independence measure (FIM) self-care subscale with real-time observations of dementia patients' ADL performance in the home.
To determine if caregivers of dementia patients can validly report (a) the level of patient activities of daily living (ADL) dependence and (b) the amount of time they spend providing ADL assistance. Seven ADLs were assessed through caregiver report using the Functional Independence Measure (FIM) and then videotaped. Videotapes were coded using a computer-assisted data collection system that documented the nature and duration of caregiver assistance provided during ADLs. The study took place in the homes of the caregiver-patient dyads. Twenty-one people with dementia and their primary caregivers participated in the study. Data analysis examined (a) the degree to which caregiver-reported FIM scores corresponded to FIM scores derived from the observational data and (b) the extent to which caregivers' estimates of ADL assistance time corresponded to the assistance time observed during ADL interactions. For all ADLs, caregiver-reported FIM scores were correlated significantly with observation-derived FIM scores (r(s) values ranged from 0.620 to 0.909), and means were similar. Assistance durations were also significantly correlated for some ADLs, but means were significantly different, indicating poor correspondence. Although caregivers of dementia patients can describe the nature of their ADL assistance with reasonable accuracy, they consistently overestimate their ADL assistance time, suggesting that caregiver reports of ADL assistance duration be used with caution. Additionally, the degree to which the assistance provided corresponds to the assistance actually needed needs to be addressed in future studies.


Impaired release of tissue plasminogen activator from the endothelium in Graves' disease - indicator of endothelial dysfunction and reduced fibrinolytic capacity.
Patients with hyperthyroidism have increased plasma levels of von Willebrand factor (vWF). Changes in tissue plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI-1), another two endothelium-derived proteins and modulators of blood fibrinolytic activity, have not been reported in hyperthyroidism. The release of t-PA by vascular endothelial cells after venous occlusion, basal blood concentrations of t-PA, PAI-1 and vWF were studied in 33 patients with hyperthyroidism, with most of them followed up 30 days after iodine radiotherapy. Compared with control subjects, both the basal t-PA levels in plasma and the increase in t-PA levels with venous occlusion were significantly decreased in patients (P < 0.001), whereas plasma PAI-1 and vWF levels were increased greatly (P < 0.001). At follow-up, patients with normal plasma free thyroxine (T4) and total tri-iodothyronine (T3) showed similar plasma levels of t-PA, PAI-1, vWF and release of t-PA from endothelial cells as the control subjects (P > 0.05). In those with persistent elevated T4 or T3 levels, however, the basal plasma t-PA level and the released t-PA from endothelial cells during venous occlusion were significantly lower than in the control subjects (P < 0.001 and P < 0.005), and blood concentrations of PAI-1 and vWF did not return to the normal range (P < 0.001 and P < 0.001). In all patients, serum thyroid hormone concentrations were inversely correlated with basal plasma t-PA (T4: r = -0.549, P < 0. 001; T3: r = -0.463, P < 0.001) and released t-PA by endothelial cells (T4: r = -0.505, P < 0.001; T3: r = -0.450, P < 0.001) but strongly correlated with plasma PAI-1 (T4: r = 0.613, P < 0.001; T3: r = 0.577, P < 0.001) and vWF (T4: r = 0.457, P < 0.001; T3: r = 0. 564, P < 0.001). Hyperthyroid patients may experience vascular endothelial dysfunction and reduced fibrinolytic activity in blood.


Epidermal adenylate cyclase system is regulated by diacylglycerol-protein kinase C signal, but not by calcium signal.
The breakdown of inositol phospholipids is an important transmembrane signalling system that is composed of two kinds of signals: the diacylglycerol-protein kinase C signal, and the inositol trisphosphate-Ca2+ signal. Using membrane-permeable diacylglycerol, I-oleoyl-2-acetylglycerol (OAG), and calcium ionophore, A-23187, the effects of these chemicals on the epidermal adenylate cyclase system were investigated. OAG increased forskolin- and cholera toxin-induced cyclic AMP accumulations, but receptor adenylate cyclase responses were markedly decreased by treatment with OAG. The effects of OAG were inhibited by the protein kinase C inhibitor, H-7. Calcium ionophore, A-23187, had no effect on the epidermal adenylate cyclase responses. Combinations of OAG and A-23187 (as well as the calcium chelator, EGTA), showed that the action of OAG was mostly unaffected by the modulation of intracellular and extracellular Ca2+ concentrations. The results suggest that among the signals triggered by the breakdown of inositol phospholipids, only diacylglycerol-protein kinase C signal is involved in the regulation of the epidermal adenylate cyclase system.


Antagonism of smooth muscle responses to oxytocin and vasopressin by salsolinol.
The responses of isolated smooth muscle tissues to the polypeptides oxytocin, vasopressin and bradykinin were evaluated in the presence of the tetrahydroisoquinoline salsolinol. Significant antagonism occurred to oxytocin and vasopressin while the effects of bradykinin were unaltered. These results suggest that the in vivo formation of salsolinol after ethanol consumption could have significant physiological consequences.


Improvement of in vitro titanium bioactivity by three different surface treatments.
Dental implants are usually made from commercially pure titanium or titanium alloys. The aim of this investigation was to determine the influence of surface treatments of commercially pure titanium samples on in vitro bioactivity. Commercially pure (cp) titanium (Ti) sheets were submitted to three different surface treatments, including, for all samples, etching with an HCl/H(2)SO(4) solution. Part of each etched sample was further submitted either to anodic oxidation by using an H(3)PO(4) solution or to thermal oxidation. Treated and non-treated samples were analyzed by using scanning electron microscopy (SEM), profilometry and photoelectron X-ray spectroscopy (XPS). The in vitro assessment was carried out through the immersion of samples in simulated body fluid (SBF). In vitro testing was carried out by SEM and by the determination of calcium (Ca) content in solution by atomic absorption spectrometry (AAS). The non-treated titanium samples were used as the control group. This study has shown that, after up to 7-day exposure, a calcium phosphate layer precipitated only on samples submitted to at least one of the three treatments used. This result, based on SEM images, is in good agreement with Ca content and XPS analysis, in which remarkable effects of surface modifications on Ti samples are highlighted. These results suggest that suitable surface treatments, such as employed here, may improve in vitro titanium bioactivity in a SBF solution at 37 degrees C. This behavior suggests a possibility of a further favorable in vivo response.


[Evaluation of applicability of HE4 and ROMA in the preoperative diagnosis of adnexal masses].
The aim of the study was to evaluate the effectiveness of HE4 alone and in combination with CA 125 (ROMA) in selecting patients at high risk of adnexal malignancy. Serum CA 125 and HE4 levels were determined and the ROMA value was calculated in 259 women qualified for surgery due to adnexal mass. The results were compared with histopathological findings. Sensitivity and specificity in preoperative diagnosis of primary ovarian cancer were 93.2% and 71.5% for CA 125 and 95.4% and 81.3% for HE4, respectively ROMA algorithm achieved sensitivity of 95.4% and specificity of 79.8%. All methods reached sensitivity of 100% at specificity of 65.6% for CA125, 93.4% for HE4 and 82.0% for ROMA in premenopausal women, whereas in postmenopausal women sensitivity and specificity achieved levels of 92.1% and 81.7% for CA 125, 94.7% and 60.6% for HE4 and 94.7% and 76.1% for ROMA, respectively Serum levels of both CA 125 and HE4 were significantly higher in women with primary ovarian cancer as compared to benign disease. Concentrations of CA 125 in patients with endometriosis were significantly elevated as compared to women with other benign tumors. Such relation was not observed when HE4 levels were concerned. CA 125, HE4 and ROMA are useful in preoperative diagnosis of ovarian malignancy HE4 improves the diagnostic accuracy in cases of endometriosis, verifying false positive results of CA 125.


Plating technique outcome evaluation in calcaneal fracture based on American orthopaedics foot and ankle score and Böhler-Gissane angle: A case series.
Intraarticular Calcaneal fracture treatment nowadays is still up for debate. Surgical plating treatment is favorable because of the rapid healing process and better anatomical reduction despite the invasive intervention. Hence, clinical evaluation is needed to assess the quality-of-life index from foot and ankle by the American orthopaedics Foot and Ankle Society (AOFAS) score postoperatively. Then, the outcome evaluation of reduction in calcaneal plating of intraarticular calcaneal fracture with Böhler angle and Gissane angle to see if the calcaneal plating technique is a recommended treatment for the calcaneal fracture. We treated six patients from December 2020-July 2021 with a calcaneal fracture that underwent surgical plating, mainly by one surgeon. A calcaneal fracture is classified according to sanders classification. In this study, four patients are above the age of 40, and two are under 25. Pre-operative Böhler angle ranged from 8 to 65°, and Gissane angle ranged from 134 to 158°. Surgical plating was performed on all six patients. From clinical evaluation using the AOFAS score, we got satisfactory results on all patients who underwent calcaneal plating surgery. Three patients achieved excellent range outcomes with 95% and 99% of AOFAS Scores, and three patients reported AOFAS score good range outcomes with the lowest score of 88%. From the radiological outcome, most of the patient's Böhler and Gissane angles achieved normal value after surgical plating. The calcaneal plating technique gives better anatomical reduction depending on Bohler and Gissane angle. These results promise that anatomical reduction can improve clinical outcomes based on the AOFAS score. Thus, the plating method can be used effectively to treat an intraarticular calcaneal fracture.


Post-session sulpiride infusions within the perifornical region of the lateral hypothalamus enhance consolidation of associative learning.
Whilst neurons within the lateral hypothalamus are well known to be responsive to the presentation of previously learned associative stimuli, the consolidation of a Pavlovian association is thought to depend in large part upon other brain regions, including the amygdala. The present study addressed this assumption directly, by examining the effect of post-session infusions of sulpiride within the lateral hypothalamus upon the acquisition of a conditioned approach response in an appetitive differential conditioning task. Subjects were exposed to an initially neutral stimulus (CS+), which immediately preceded the availability of a 10% sucrose reward (US). A second, control stimulus (CS ) was also presented. but never in close temporal proximity to the US. The number and duration of alcove approaches were recorded. Immediately following each training session, subjects were infused bilaterally with sulpiride (0, 0.5, 5 microg) in the vicinity of the perifornical region of the lateral hypothalamus. Sulpiride dose-dependently enhanced the rate of acquisition of a conditioned approach response to presentation of the CS+, but was without affect upon approach behaviour during CS(-) or US presentations. Thus, 0.5 microg sulpiride facilitated at an early stage (session 2 onwards) the number of alcove approaches to the CS+, while 5 microg sulpiride enhanced to a greater extent the duration of conditioned approach, particularly during later sessions. A subsequent locomotor test using 0.5 mg/kg d-amphetamine indicated that repeated infusions of the higher dose sulpiride (5 microg), but not the lower dose (0.5 microg), resulted in behavioural sensitisation to administration of the psychomotor stimulant. Acquisition of a novel conditioned instrumental response was not affected by previous exposure to sulpiride. These data suggest that dopamine-sensitive neurons within the lateral hypothalamus may play a significant role in the acquisition of appetitive Pavlovian associations.


The development of Panstrongylus herreri under fluctuating environmental conditions.
Panstrongylus herreri is a main Chagas disease vector, and its success as a vector stems from its ability to establish domiciliated colonies; we aimed to explore its biology and reproduction. The average amount of blood ingested and the time from the beginning of a blood meal to the production of feces were recorded. Females exhibited a higher blood ingestion rate than males, but similar defecation times and frequencies were observed. Despite the detected decrease in oviposition rates, P. herreri's potential as a Chagas disease vector in environments other than the Amazon forest cannot be discounted.


Correction to: Periodontal Disease Impairs Muscle Recovery by Modulating the Recruitment of Leukocytes.
The original version of this article contained mistakes, and the authors would like to correct them.


Practical implementation and clinical benefits of the new automated dialysate sodium control biosensor.
A key feature of dialysis treatment is the prescription of dialysate sodium (Na). This study aimed to describe the practical implementation of a new automated dialysate Na control biosensor and to assess its tolerance and the beneficial clinical effects of isonatraemic dialysis. A prospective study was carried out in 86 patients who, along with their usual parameters, received the following five consecutive phases of treatment for 3 weeks each: phase 0: baseline 5008 machine; phases 1 and 2: 6008 machine without activation of the Na control biosensor and the same fixed individualized Na dialysate prescription or adjusted to obtain similar conductivity to phase 0; phases 3 and 4: activated Na control to isonatraemic dialysis (Na dialysate margins 135-141 or 134-142 mmol/L). When the Na control was activated, the few episodes of cramps or hypotension disappeared when the lower dialysate Na margin was increased by 1 or 2 mmol/L. The activated Na control module showed significant differences compared with baseline and the non-activated Na module in final serum Na values, diffusive Na balance, and changes in pre- to postdialysis plasma Na values. The mean predialysis systolic blood pressure value was significantly lower in phase 4 than in phase 1. There were no significant differences in total Na balance in the four 6008 phases evaluated. The implementation of the automated dialysate Na control module is a useful new tool, which reduced the diffusive load of Na with good tolerance. The module had the advantages of reducing thirst, interdialytic weight gain and intradialytic plasma Na changes.


Alpha detection: some comments on Hardt and Kamiya, "Conflicting results in EEG alpha feedback studies".
The problem of defining EEG alpha activity, and of detecting and measuring it, is outlined. Some advantages of a threshold method are presented and compared with an amplitude-integration method. Characteristics of percent-time scoring, based upon observable alpha spindles in the waking EEG, are discussed. A probability distribution of percent-time alpha as a function of detection threshold is derived and compared with empirical data.


Preparation and evaluation of dual drug-loaded nanofiber membranes based on coaxial electrostatic spinning technology.
Wound healing is a complicated process consisting of wound bleeding, inflammatory response, cell proliferation and tissue remodeling. During this long-term period, wound is vulnerable to infection by bacteria or microbes. Therefore, we prepared a novel centella total glucoside-ciprofloxacin dual-loaded coaxial nanofiber membrane (CDCNM) by using coaxial electrostatic spinning technique. To satisfy personalized therapeutic demands by adjusting release behaviors, we loaded centella total glucoside (CTG) and ciprofloxacin (CIP) into different positions of the fibers and the morphology and coaxial structure of the nanofiber membranes were analyzed by SEM and TEM. In addition, water contact angle, water absorption capacity, breathability and in vitro drug release were tested. In vitro cell experiments demonstrated that CDCNM can promote fibroblast proliferation. CDCNM demonstrated excellent antimicrobial activity through the agar flat dish diffusion method. Furthermore, rat scald experiments showed that CDCNM significantly accelerated scald healing, meanwhile immunohistochemical staining showed that CDCNM promoted the expression of CD31 and VEGF during early wound healing, which accelerated scald healing by promoting neovascularization and endothelial cell proliferation. As a topical multifunctional wound dressing, this dual drug-loaded nanofiber membrane achieved scald healing effect and continuous bacterial inhibition, which provides new ideas for existing trauma treatment tools and dual drug delivery systems.


The effects of ozone on lung, heart, and liver superoxide dismutase and glutathione peroxidase activities in the protein-deficient rat.
The effects of protein deficiency or food restriction and ozone exposure on lung, heart and liver superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities were studied in weanling and adult rats. Two groups of rats were fed diets containing 4 or 16% protein. A third group was fed the 16% protein diet, but at the level consumed by the rats fed the 4% protein diet. After 3 weeks (weanling) or 5 weeks (adult), one-half of the rats in each group were exposed continuously to 0.64 ppm ozone for 7 days. In adult rat lung, O3 exposure typically stimulated Cu,Zn-SOD and GPx activities in all groups, but in weanling rats only GPx activity was elevated and only in rats fed the 16% protein diet. Liver Cu,Zn-SOD activity was also influenced by diet; in adult rats, liver Mn-SOD and GPx activities were often depressed following O3 exposure. Heart SOD and GPx, however, were not affected by ozone or diet. The pulmonary and hepatic effects due to diet and O3 further illustrate the importance of nutritional status when assessing the health effects of O3 exposure.


Putative stem cell activity of human endometrial epithelial and stromal cells during the menstrual cycle.
To determine whether menstrual cycle stage or activity has an effect on the clonogenic activity of human endometrial epithelial and stromal cells. Clonal analysis of human endometrial epithelial and stromal cells derived from full-thickness endometrium. University research laboratory. Twenty-six women of varying age and race undergoing hysterectomy for nonendometrial pathologies. Full-thickness human endometrial tissue was dissociated into single cells. Epithelial and stromal cells were separated using magnetic beads, and cloning assays were performed in serum-containing or growth factor-supplemented serum-free medium. Clonogenic activity of epithelial and stromal cells. Clonogenicity of epithelial and stromal cells did not vary significantly between proliferative, secretory, and inactive endometrium. However, epithelial and stromal cells did show a trend for greater numbers of clonogenic cells in secretory and proliferative endometrium respectively. A large variation between samples was observed, which may have masked any significant differences. We found that clonogenicity does not vary from the proliferative to secretory stage of the menstrual cycle, or between active, cycling and inactive endometrium for both epithelial and stromal cells. We have demonstrated for the first time that inactive endometrium contains clonogenic epithelial and stromal cells.


A randomized comparison of locking and non-locking palmar plating for unstable Colles' fractures in the elderly.
This study compared the effectiveness of locking and non-locking palmar plating for unstable Colles' fractures in the elderly. The patients treated with locking plates included 4 men and 18 women with a mean age of 68 years (Group A) and those treated with non-locking plates included 3 men and 28 women with a mean age of 74 years (Group B). Radiographic parameters, including palmar tilt, radial inclination and radial length were measured before surgery, after surgery and at final followup. There were no significant differences in respect of any of the radiographic parameters between the two groups pre-operatively. After surgery, all of the radiographic parameters were improved in both groups and there were no significant differences between the two groups at final followup.


Phenidone prevents kainate-induced neurotoxicity via antioxidant mechanisms.
Acculmulating evidence indicates that a marked generation of oxygen free radicals derived from the metabolism of arachidonic acid causes neurodegeneration. Recently, we have demonstrated that the novel antioxidant actions mediated by phenidone, a dual inhibitor of cyclooxygenase/lipoxygenase pathways, may play a crucial role in preventing neuroexcitotoxicity in vitro [Neurosci. Lett. 272 (1999) 91], and that phenidone significantly attenuates kainic acid (KA)-induced seizures via inhibiting the synthesis of Fos-related antigen protein [Brain Res. 782 (1998) 337]. In order to extend our understanding of the pharmacological intervention of phenidone, we evaluated the antioxidant activity of this compound in vivo in the present study. In order to better understand the significance of a blockade of both the cyclooxygenase and lipoxygenase pathways, we studied the effects of aspirin (ASP; a non-selective inhibitor of cyclooxygenase), NS-398 (a selective inhibitor of cyclooxygenase-2), esculetin (an inhibitor of lipoxygenase) and phenidone on lipid peroxidation, protein oxidation, and glutathione (GSH) status in the rat hippocampus after KA administration. ASP (7.5 or 15 mg/kg), NS-398 (10 or 20 mg/kg), esculetin (5 or 10 mg/kg) or phenidone (25, 50 or 100 mg/kg) was administered orally five times every 12 h before the injection of KA (10 mg/kg, i.p.). The KA-induced toxic behavioral signs, oxidative stress (lipid peroxidation and protein oxidation), impairment of GSH status, and the loss of hippocampal neurons were dose-dependently attenuated by the phenidone, NS-398+esculetin, and ASP+esculetin. However, ASP, NS-398 and esculetin alone failed to protect against the neurotoxicities induced by KA. Therefore, the results suggest that protection by blockade of both cyclooxygenase and lipoxygenase pathways against KA-induced neuroexcitotoxicity is via antioxidant actions. However, a novel anticonvulsant/neuroprotective effect mediated by phenidone remains to be further characterized.


Retained appendicolith in an inflamed appendix.
Risk factors for progression to advanced appendicitis have not been clarified. The purpose of this study was to investigate whether the presence of appendicolith on computed tomography (CT) is related to progression of pathologic grade. We performed a retrospective review of 46 consecutive patients who underwent appendectomy and who had an inflamed appendix on CT scan. Patients were divided into two groups: group A underwent CT scan within 10 h of onset of symptoms, and group B was scanned after more than 10 h of symptoms. The presence or absence of appendicolith on CT as well as pathologic inflammatory grade was recorded. We analyzed correlation between the presence of appendicolith and ultimate pathologic grade in each group. Appendicoliths were detected on CT in 17 (17/36) of group B. The presence of appendicolith on CT in group B was significantly correlated with pathologic severity (p = 0.006). Retained appendicolith that is identified in an inflamed appendix on CT more than 10 h after onset of symptoms may be useful as a predictor of pathologic inflammatory grade of appendicitis.


Sagittal mandibular changes with overbite correction in subjects with different mandibular growth directions: late mixed-dentition treatment effects.
This study involved the assessment of pretreatment and posttreatment lateral cephalograms from late mixed-dentition patients with Class II Division 1 and Division 2 malocclusions with mild mandibular crowding. All were selected before treatment began. Combined growth and treatment effects were compared with changes in untreated subjects. The study was designed specifically to determine whether anteroposterior mandibular dentoalveolar and skeletal changes associated with reduction of deep incisal overbites, by using a particular late mixed-dentition treatment approach, are influenced by the direction of mandibular growth during treatment. In mesofacial and brachyfacial subjects, significantly greater forward movements were found at Point B after deep overbite correction than in dolichofacial subjects. This apparently enhanced effect compared with the untreated controls was not seen at pogonion. Clinicians should expect considerably greater forward movement of the mandibular dentoalveolus with normal mandibular growth after incisal bite opening in mesofacial and brachyfacial patients. As a consequence, less maxillary retraction might be necessary in growing mesofacial and brachyfacial Class II Division 1 and Division 2 patients than in dolichofacial patients. On the other hand, one should not expect enhancement of basal sagittal mandibular growth, regardless of the underlying vertical facial pattern.


PfAlba1: master regulator of translation in the malaria parasite.
During the asexual replication cycle of the malaria parasite Plasmodium falciparum, the RNA-binding protein PfAlba1 binds and stabilizes a subset of transcripts for translation at a later time point.Please see related Research article: http://www.genomebiology.com/2015/16/1/212.


Localization of calcitonin gene-related peptide-like immunoreactivity in neurons of the rat gastrointestinal tract.
Calcitonin gene-related peptide (CGRP)-like immunoreactivity was localized in neuronal processes and somata of the rat gastrointestinal tract. Varicose processes were observed in the myenteric and submucosal plexuses, smooth muscles, submucosa, mucosa and around blood vessels. Immunoreactive somata were visualized in the myenteric and submucosal ganglia of the intestine in colchicine-treated rats. These observations, together with previous neuroanatomical and pharmacological studies, suggest that CGRP may be involved in regulatory functions of the gastrointestinal tract.


Serum nicotinamide adenine dinucleotide levels through disease course in multiple sclerosis.
The levels of the essential pyridine nucleotide, NAD(+) and its reduced form NADH have not been documented in MS patients. We aimed to investigate NAD(+) and NADH levels in serum in patients with different disease stages and forms of MS. NAD(+) and NADH levels were measured in the serum from 209 patients with relapsing remitting MS (RRMS), 136 with secondary progressive MS (SPMS), 51 with primary progressive MS (PPMS), and 99 healthy controls. All patients were in a clinically stable phase. Serum NAD(+) levels declined by at least 50% in patients with MS compared to controls (17.9 ± 3.2 μg/ml; p=0.0012). Within the MS sub-groups NAD(+) levels were higher in RRMS (9.9 ± 2.9 μg/ml; p=0.001) compared to PPMS (6.3 ± 2.1 μg/ml; p=0.003) and SPMS (7.8 ± 2.0 μg/ml; p=0.005). A two-fold increase in NADH levels (p=0.002) and at least three-fold reduction in the NAD(+)/NADH ratio (p=0.009) were observed in MS patients compared to controls. Serum NAD(+) and NADH levels are may be associated with disease progression in MS. Given the importance of NAD(+) in the maintenance of normal cellular function, it is likely that this molecule is of therapeutic relevance in MS.


Characteristic facies in type B brachydactyly?
We report a family with type B brachydactyly. The distinctive facial appearance of those affected raises the possibility of an association.


Assembly rules for Greater Antillean Anolis lizards : Competition and random models compared.
Using previously published data, several models were constructed to predict the distribution of Anolis lizard species on a set of sites on Puerto Rico and Jamaica. The models form a series with increasing ecological detail. The simpler "null" models are based on randomly created species-site matrices using progressively greater dependency on the observed matrix. The remaining models hypothesize that competition is the most important biotic interaction determining the intra-island distribution of the lizards. "Simple" competition models test the predictive power of simple statistical descriptions relating intensity of competition and ecological variables such as niche overlap and body size ratios. More complicated models are based on the ecomorph model of Williams (1972) and use the lizard resourceuse data of several niche dimensions (e.g., perch diameter and height). These models are derived from Puerto Rican data and tested against Jamaican data. The primary statistical tool used to test the accuracy of these models in the kappa statistic (Fleiss 1973) which assesses the degree of agreement in a contingency table relative to that expected by chance. The model structure is based on generative grammars (Haefner 1981), but is also related to artificial intelligence expert systems. Model comparisons indicate the following. (1) Only those null models constrained by the marginals of the observed species-site matrix agree with observed data. (2) Simple competition models based on fixed size ratios and/or fixed levels of allowable overlap do not agree well. (3) A complex competition model developed for Puerto Rico also shows significant agreement with lizard distributions on Jamaica, but is not better than a constrained null model. (4) If allowance is made for the restricted distribution of A. sagrei, a recent colonist of Jamaica, agreement of the competition model increases dramatically. It is predicted that A. sagrei would persist following an experimental transplant to eastern Jamaica.


Diffuse dermal neutrophilia in urticaria.
Twenty-three cases of diffuse dermal neutrophilia and urticaria were reviewed. Evidence of vasculitis or other disease was not present. Direct immunofluorescence was done in 19 cases and was positive but nonspecific in 14. The presence of angioedema (10 cases), dermographism (2 cases), atopy (4 cases), drug reactions (6 cases), and infections (6 cases) was similar to that seen in cases of urticaria without diffuse dermal neutrophilia. Nearly 9% of the cases of urticaria show this histologic pattern, and when cases of neutrophilic urticaria are added, 15.8% of cases of urticaria were found to show a major neutrophil component in the inflammation. In urticaria, neutrophilia may be part of an intense stimulus response pattern.


Oxygen free radicals and myocardial reperfusion injury.
Diseases involving tissue reperfusion following ischemia are gaining significance in emergency medicine. The significance of reperfusion injury and the probable role of oxygen-derived free radicals has been described in many tissues, particularly the heart. During myocardial reperfusion a burst of oxygen-derived free radicals overwhelms normal cellular defenses. These radicals may have several detrimental effects. They can oxidize lipids, leading to membrane dysfunction. They can also alter nucleic and other proteins. Cellular dysfunction and death may ensue. Prevention of oxygen-derived free radical injury appears possible and may be feasible for several disease processes, including myocardial reperfusion after infarction.


Provider Attitudes Toward Risk-Based Hepatocellular Carcinoma Surveillance in Patients With Cirrhosis in the United States.
Hepatocellular carcinoma (HCC) surveillance rates are suboptimal in clinical practice. We aimed to elicit providers' opinions on the following aspects of HCC surveillance: preferred strategies, barriers and facilitators, and the impact of a patient's HCC risk on the choice of surveillance modality. We conducted a web-based survey among gastroenterology and hepatology providers (40% faculty physicians, 21% advanced practice providers, 39% fellow-trainees) from 26 US medical centers in 17 states. Of 654 eligible providers, 305 (47%) completed the survey. Nearly all (98.4%) of the providers endorsed semi-annual HCC surveillance in patients with cirrhosis, with 84.2% recommending ultrasound ± alpha fetoprotein (AFP) and 15.4% recommending computed tomography (CT) or magnetic resonance imaging (MRI). Barriers to surveillance included limited HCC treatment options, screening test effectiveness to reduce mortality, access to transportation, and high out-of-pocket costs. Facilitators of surveillance included professional society guidelines. Most providers (72.1%) would perform surveillance even if HCC risk was low (≤0.5% per year), while 98.7% would perform surveillance if HCC risk was ≥1% per year. As a patient's HCC risk increased from 1% to 3% to 5% per year, providers reported they would be less likely to order ultrasound ± AFP (83.6% to 68.9% to 57.4%; P < .001) and more likely to order CT or MRI ± AFP (3.9% to 26.2% to 36.1%; P < .001). Providers recommend HCC surveillance even when HCC risk is much lower than the threshold suggested by professional societies. Many appear receptive to risk-based HCC surveillance strategies that depend on patients' estimated HCC risk, instead of our current "one-size-fits all" strategy.


The characteristics of short- and long-term surviving Shiba dogs with chronic enteropathies and the risk factors for poor outcome.
The objectives of this study were to investigate the differences in the characteristics of short- and long-term surviving dogs, and the factors that predict poor outcome in Shiba dogs with chronic enteropathies (CE). A total of 25 Shiba dogs were included in this study, and classified as either short-term (≤6 months) survivors (Ss; n=16) or long-term (>6 months) survivors (Ls; n=9). The clinical and clinicopathological variables, histopathology, response to therapy, and outcomes were investigated between groups. Furthermore, these factors were tested for their ability to predict poor outcome. All CE dogs were diagnosed as having inflammatory bowel disease (IBD) with lymphocytic-plasmacytic enteritis (LPE). Age and canine inflammatory bowel disease activity index (CIBDAI) were significantly higher in the Ss group than in the Ls group (age: p = 0.035, CIBDAI: p = 0.018), as determined via univariate logistic regression analysis. According to receiver operator characteristic (ROC) curve analysis, the best predictors of poor outcome were age and CIBDAI, with the cutoffs determined as 7 years and 9 points, respectively. The majority of the cases (84%) responded to initial treatment; in particular, 75% of dogs in Ss group responded to therapy. The time to response (days) to the initial treatment in the Ss group (median 42.5 days, range: 20-91 days) was significantly shorter than that of the Ls group (median 285 days, range: 196-1026 days). Approximately half (55.5%) of the dogs in the Ls group died due to relapse of CE. This study suggested that there is a high risk of early mortality in Shiba dogs with CE, particularly if the dogs are older (>7 years) and have a high CIBDAI score (>9 points). There appears to be a possibility of early mortality even if the initial treatment was efficacious. Furthermore, Shiba dogs with CE that become less responsive to initial therapy in the short-term (approximately 3 months) are more likely to have an early mortality. Thus, it is necessary to follow-up Shiba dogs with CE in the long-term, as approximately half of the long-term survivors eventually died due to a relapse of the signs.


Synthesis and characterization of glucosyl stevioside using Leuconostoc dextransucrase.
Glucosyl stevioside was synthesized via transglucosylation by dextransucrase from Leuconostoc citreum KM20 (LcDexT), forming α-d-glucosyl stevioside. A production yield of 94% was reached after 5days of LcDexT reaction at 30°C. Glucosyl stevioside induced a 2-fold improved quality of taste and sweetness, compared to stevioside. After 15days of storage at 25°C, 98% of glucosyl stevioside in an aqueous solution was present in a soluble form, compared to only 11% for stevioside or rebaudioside A. Furthermore, glucosyl stevioside exhibited a similar or improved stability in commercially available soft drinks, when compared to stevioside and rebaudioside A. These results suggest that glucosyl stevioside could serve as a highly pure and stable sweetener in soft drinks.


Oral and Maxillofacial Surgery and Oral Surgery - what's the difference? A Western Australian dental student survey.
Confusion exists around the terms 'Oral Surgeon' and 'Oral and Maxillofacial Surgeon'. Historical terms and international differences have added to this confusion. Recently, the University of Sydney has begun to offer a Doctor of Clinical Dentistry in Oral Surgery to graduate dentists. With this new dental specialty entering the Australian workforce, distinction must be made between their role and the role of Oral and Maxillofacial Surgeons to facilitate effective referral pathways. A cross sectional survey of 3rd and 4th year dental students was distributed in June 2019. Students were queried with regards to their perception of the scope of practice of Oral Surgeons and Oral and Maxillofacial Surgeons as well as their knowledge of the training pathways and level of interest in pursuing either pathway. A total of 85% of students responded. Responses indicated a general awareness of the increased scope of practice of Oral and Maxillofacial Surgeons with some exceptions. No significant difference was seen between third and fourth year responses. Knowledge of both training pathways was lacking. Further education is required with regards to the scope of practice of both specialties. A lack of exposure to Oral and Maxillofacial Surgery during the undergraduate years may be partly to blame. Consideration should be given to the renaming of Oral Surgery to Surgical Dentistry.


Nonmyeloablative allogeneic bone marrow transplantation as immunotherapy for hematologic malignancies and metastatic solid tumors in preclinical models.
We previously demonstrated that a combination of mild total lymphoid irradiation (TLI) with selective depletion of the host's donor-reactive cells allows for stable and graft-vs-host disease (GVHD)-free engraftment of allogeneic bone marrow (BM). In this study, we investigated the efficacy of this nonmyeloablative strategy for BM transplantation (BMT) as immunotherapy for minimal residual disease. BALB/c mice inoculated with leukemia (BCL1) or breast carcinoma (4T1) cells were conditioned for BMT with TLI (200 cGy) followed by priming with donor (C57BL/6) BM cells on day 1, and by injection with 200 mg/kg cyclophosphamide on day 2. After conditioning (day 3), recipients were transplanted with BM cells from the same donor. Treated animals were monitored for 230 days for survival, development of leukemia/solid tumor, and GVHD. BMT converted the mice to complete chimeras and prevented development of leukemia in 90% of recipients and locally growing breast carcinoma in 40% of the mice. Immunization of donors of the second BM with 4T1 cells prevented development of breast carcinoma in 80% of 4T1 inoculated mice. Fewer animals treated for malignancy by nonmyeloablative BMT died of GVHD than those treated by myeloablative BMT. However, late GVHD-related mortality in mice treated for leukemia was higher than after nonmyeloablative BMT to naive recipients (p < 0.00001). Infusion of host-type anti-donor immune lymphocytes 8 days after BMT improved the survival of recipients treated for leukemia without affecting engraftment and the graft-vs-leukemia potential of donor BM. Effective eradication of malignant cells can be achieved following allogeneic BMT after nonmyeloablative conditioning.


Evaluation of Maternal Complications in Severe Preeclampsia in a University Hospital in Tirana.
Preeclampsia is a hypertensive multisystem disorder of pregnancy that complicates up to 10% of pregnancies worldwide and is one of the leading causes of maternal and perinatal morbidity and mortality. To evaluate maternal complications associated with severe preeclampsia. This is a retrospective cross-sectional study conducted in the UHOG "Koço Gliozheni", in Tirana. Primary outcomes evaluated: maternal death, eclampsia, stroke, HELLP syndrome, and pulmonary edema. renal failure, admission in ICU, caesarean section, placental abruption, and postpartum hemorrhage. Fisher's exact test and Chi-squared test were used as statistical methods. In women with severe preeclampsia we found higher rates of complications comparing to the group with preeclampsia. Eclampsia (1.5% vs. 7.1%, P < 0.001), HELLP syndrome (2.4% vs. 11.0%; P < 0.001), stroke (0.5% vs 1.9%, P = 0.105) pulmonary edema (0.25% vs. 1.3%, P = 0.0035), renal failure (0.9% vs. 2.6%, P = 0.107), admission in ICU (19.5% vs. 71.4%, P = 0.007), caesarean section rates (55.5% vs. 77%, P = 0.508), placental abruption (4.3% vs. 7.8%, P = 0.103) and severe postpartum hemorrhage (3.2% vs. 3.9%, P = 0.628). Severe preeclampsia is associated with high rates of maternal severe morbidity and early diagnosis and timely intervention can prevent life treating complications.


Mechanism of beta 1-integrin-mediated hepatoma cell growth involves p27 and S-phase kinase-associated protein 2.
Although cooperative interactions between growth factors and integrins, cell surface receptors for extracellular matrices (ECM), have been reported, little is known about the interaction between hepatocyte growth factor (HGF) and integrin in hepatoma cells. We investigated the effects and mechanisms of integrin on the proliferation of hepatoma cells regulated by HGF. Human HepG2 hepatoma cells stably transfected with beta 1-integrin were treated with HGF and compared with parental and mock-transfected control cells. Cell proliferation and expression of cyclin-dependent kinase (Cdk) inhibitors and S-phase kinase-associated protein 2 (Skp2), were investigated. HGF dose-dependently suppressed the proliferation of parental and mock-transfected HepG2 cells. However, cells overexpressing beta 1-integrin exhibited increased proliferation in response to HGF. Although HGF increased p27 and decreased Skp2 expression in the parental and mock-transfected cells, the p27 and Skp2 levels in cells overexpressing beta 1-integrin were not altered by HGF. Interestingly, HepG2 cells overexpressing beta 1-integrin showed increased Skp2 expression. Furthermore, HGF did not reduce the proliferation of HepG2 cells transfected with antisense p27 or sense Skp2. Thus, HGF suppresses HepG2 cell proliferation by directly increasing p27 expression and indirectly decreasing Skp2 expression, and beta 1-integrin modulates the responsiveness of hepatoma cells to HGF via a p27-dependent manner by increasing Skp2. In conclusion, these results strongly suggest that integrin-mediated signals from the ECM can modulate growth factor-mediated signals in hepatoma cells, and may contribute to the growth of hepatocellular carcinomas.


A synthetic 13-residue peptide corresponding to the hydrophobic region of bovine seminalplasmin has antibacterial activity and also causes lysis of red blood cells.
Seminalplasmin (SPLN), a 47-residue peptide present in bovine seminal plasma, is one of the few proteins isolated from mammalian sources having potent antibacterial activity. SPLN also interacts with sperm acrosomal and plasma membranes. On the basis of analysis of the primary structure of SPLN with respect to its relative hydrophobicity and hydrophilicity, a region comprising of 13-amino acids, Pro-Lys-Leu-Leu-Glu-Thr-Phe-Leu-Ser-Lys-Trp-Ile-Gly, has been delineated. It is demonstrated that a synthetic peptide corresponding to this 13-residue region inhibits growth of Escherichia coli like SPLN and also has the ability to lyse red blood cells.


Online survey of university students' perception, awareness and adherence to COVID-19 prevention measures.
Determining factors correlated with protective measures against COVID-19 is important to improve public health response. This study describes student opinions related to university COVID-19 preventive measures. In fall 2020, 643 US university students completed an online survey on perception, awareness, and adherence to COVID-19 preventive measures. Outcomes included protocol effectiveness (self or others), protocol adherence (self or others), consequences of protocol violation, knowledge of violations, and level of concern for COVID-19. Multiple linear regression models determined correlates of outcome variables. Covariates included gender, race, residence, area of study, class, and knowledge of someone with a positive COVID-19 test. Overall, students agreed with protective measures (equivalent to higher scores). In adjusted linear models, females (versus males) had significantly higher scores for protocol effectiveness (self) (p < 0.001), consequences of protocol violation (p = 0.005), and concern about COVID-19 (p < 0.001). Asian/Pacific Islander (versus white) had significantly higher scores for protocol effectiveness (self) (p < 0.001), consequences of protocol violation (p = 0.008), and concern about COVID-19 (p = 0.001). Graduate students (versus freshman) had higher scores for protocol effectiveness (self) (p < 0.001), protocol adherence (self) (p = 0.004) and concern about COVID-19 (p < 0.001). In contrast, participants who had a positive COVID-19 test had significantly lower scores for protocol effectiveness (self) (p = 0.02), protocol adherence (self) (p = 0.004), and consequences of protocol violation (p = 0.008). Overall, females, Asian/Pacific Islanders, and graduate students were more likely to agree with or adhere to COVID-19 prevention guidelines but those who tested positive for COVID-19 were less likely to do so. These results may inform future prevention efforts.


Next-generation sequencing identifies high frequency of mutations in potentially clinically actionable genes in sebaceous carcinoma.
Sebaceous carcinoma (SC) is a rare but aggressive malignancy with frequent recurrence and metastases. Surgery is the mainstay of therapy, but effective systemic therapies are lacking because the molecular alterations driving SC remain poorly understood. To identify these, we performed whole-exome next-generation sequencing of 409 cancer-associated genes on 27 SCs (18 primary/locally recurrent ocular, 5 paired metastatic ocular, and 4 primary extraocular) from 20 patients. In ocular SC, we identified 139 non-synonymous somatic mutations (median/lesion 3; range 0-23). Twenty-five of 139 mutations (18%) occurred in potentially clinically actionable genes in 6 of 16 patients. The most common mutations were mutations in TP53 (n = 9), RB1 (n = 6), PIK3CA (n = 2), PTEN (n = 2), ERBB2 (n = 2), and NF1 (n = 2). TP53 and RB1 mutations were restricted to ocular SC and correlated with aberrant TP53 and RB protein expression. Systematic pathway analyses demonstrated convergence of these mutations to activation of the PI3K signalling cascade, and PI3K pathway activation was confirmed in tumours with PTEN and/or PIK3CA mutations. Considerable inter-tumoural heterogeneity was observed between paired primary and metastatic ocular SCs. In primary extraocular SC, we identified 77 non-synonymous somatic mutations (median/lesion 22.5; range 3-29). This overall higher mutational load was attributed to a microsatellite instability phenotype in three of four patients and somatically acquired mutations in mismatch repair genes in two of four patients. Eighteen of 77 mutations (23%) were in potentially clinically actionable genes in three of four patients, including BTK, FGFR2, PDGFRB, HRAS, and NF1 mutations. Identification of potentially clinically actionable mutations in 9 of 20 SC patients (45%) underscores the importance of next-generation sequencing to expand the spectrum of genotype-matched targeted therapies. Frequent activation of PI3K signalling pathways provides a strong rationale for application of mTOR inhibitors in the management of this disease. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.


The relation between serum phosphorus levels and clinical outcomes after acute myocardial infarction.
Elevated serum phosphorus levels have been linked with cardiovascular disease and mortality with conflicting results, especially in the presence of normal renal function. We studied the association between serum phosphorus levels and clinical outcomes in 1663 patients with acute myocardial infarction (AMI). Patients were categorized into 4 groups based on serum phosphorus levels (<2.50, 2.51-3.5, 3.51-4.50 and >4.50 mg/dL). Cox proportional-hazards models were used to examine the association between serum phosphorus and clinical outcomes after adjustment for potential confounders. The mean follow up was 45 months. The lowest mortality occurred in patients with serum phosphorus between 2.5-3.5 mg/dL, with a multivariable-adjusted hazard ratio of 1.24 (95% CI 0.85-1.80), 1.35 (95% CI 1.05-1.74), and 1.75 (95% CI 1.27-2.40) in patients with serum phosphorus of <2.50, 3.51-4.50 and >4.50 mg/dL, respectively. Higher phosphorus levels were also associated with increased risk of heart failure, but not the risk of myocardial infarction or stroke. The effect of elevated phosphorus was more pronounced in patients with chronic kidney disease (CKD). The hazard ratio for mortality in patients with serum phosphorus >4.5 mg/dL compared to patients with serum phosphorus 2.50-3.50 mg/dL was 2.34 (95% CI 1.55-3.54) with CKD and 1.53 (95% CI 0.87-2.69) without CKD. We found a graded, independent association between serum phosphorus and all-cause mortality and heart failure in patients after AMI. The risk for mortality appears to increase with serum phosphorus levels within the normal range and is more prominent in the presence of CKD.


The effect of ascorbate on essential fatty acid composition in B16 melanoma cells.
Ascorbate has been shown to be involved in essential fatty acid (EFA) metabolism, resulting in the suggestion that the effect of ascorbate on cell growth may be mediated through an influence on the metabolism of these FAs. This study examined the effect of ascorbate, supplemented over the nutritional concentration range of 0-100 micrograms/ml, on the in vitro cell growth of non-malignant LLCMK (monkey kidney) cells and malignant B16 murine melanoma cells. The effect of ascorbate on EFA composition was also investigated, and involved the determination of the levels of linoleic acid (LA), gamma-linoleic acid (GLA), dihomogammalinolenic acid (DGLA) and arachidonic acid (AA) present in the stroma and membrane of the two cell types. Ascorbate had no significant inhibitory or stimulatory effect on the growth of either the LLCMK or B16 cells. EFA levels detected in the LLCMK cells were generally higher than those detected in the B16 cells. The % composition of the various EFAs in the stroma fractions of the two cell types were higher than the level of the corresponding EFAs in the membrane fractions. GLA levels were not detectable in the membrane fractions of the B16 cells. AA % composition determined in both cell types, was greater than that of any other EFA % composition.


Clinical significance of the number of oligoclonal bands in patients with clinically isolated syndromes.
CSF oligoclonal bands (OCBs) in patients with clinically isolated syndromes (CIS) are a risk factor for clinically definite multiple sclerosis (CDMS). We aimed to address the relevance of the number of OCBs in the prognosis of CIS patients. 219 CIS patients were included in the study, and 42% of them developed the disease during follow-up (median: 5.04 years). Patients with a high number of CSF OCBs (third quartile, 8-12 OCBs) had 2.5-fold increase in CDMS risk, while no further increase in the HR of disease was observed for patients with more than 12 OCBs. The results did not change after adjustment for additional correlates of CDMS development. This association may be due to the epitope-spreading phenomenon and may reflect the stage of the disease at the time of the examination.


[Stabilizing effect of hydroxybenzimidazole and its derivatives on biological membranes during activation of lipid peroxidation].
Inhibition of lipid peroxidation (LPO) by oxybenzimidazole (OBI) and its derivatives--alkyloxybenzimidazole (AOBI) and alkylethoxybenzimidazole (AEBI) was studied in liver microsomes and brain synaptosomes. It has been shown that both OBI and AOBI strongly inhibit LPO in microsomes and not synaptosomes. AEBI failed to inhibit LPO in microsomes. AOBI is more potent than OBI both in ascorbate- and NADPH-dependent LPO of microsomes. An antioxidant effect of both compounds is more marked in ascorbate-dependent LPO. The investigation of the possible use of AOBI for the protection of liver membranes in various pathological conditions associated with LPO activation seems promising.


Systematic interactome mapping and genetic perturbation analysis of a C. elegans TGF-beta signaling network.
To initiate a system-level analysis of C. elegans DAF-7/TGF-beta signaling, we combined interactome mapping with single and double genetic perturbations. Yeast two-hybrid (Y2H) screens starting with known DAF-7/TGF-beta pathway components defined a network of 71 interactions among 59 proteins. Coaffinity purification (co-AP) assays in mammalian cells confirmed the overall quality of this network. Systematic perturbations of the network using RNAi, both in wild-type and daf-7/TGF-beta pathway mutant animals, identified nine DAF-7/TGF-beta signaling modifiers, seven of which are conserved in humans. We show that one of these has functional homology to human SNO/SKI oncoproteins and that mutations at the corresponding genetic locus daf-5 confer defects in DAF-7/TGF-beta signaling. Our results reveal substantial molecular complexity in DAF-7/TGF-beta signal transduction. Integrating interactome maps with systematic genetic perturbations may be useful for developing a systems biology approach to this and other signaling modules.


[Circahoral rhythms of quantitative protein change--a marker of the morphological maturity and functional activity of the retina].
The development of hour changes in the protein content of the retinal ganglionic cells was studied in 1, 7, 14, 19, and 30 day old ground squirrels using cytophotometry. Such rhythms were also compared in sexually mature active and hibernating animals. In ground squirrels, as well as in the other immature born mammals, the recording of hour rhythms of the protein content of the ganglionic neurones becomes possible only after the morphological maturation of retina, from the 19th day of postnatal ontogenesis. During hibernation, no hour rhythms of the protein content of the retina ganglionic cells were recorded in ground squirrels. A conclusion has been drawn that the hour rhythms of protein metabolism can serve as an index of morphological maturity of the tissue and its functional activity.


The exact vs. approximate distinction in numerical cognition may not be exact, but only approximate: How different processes work together in multi-digit addition.
Two types of calculation processes have been distinguished in the literature: approximate processes are supposed to rely heavily on the non-verbal quantity system, whereas exact processes are assumed to crucially involve the verbal system. These two calculation processes were commonly distinguished by manipulation of two factors in addition problems: the identity of the target and the distance of the distractor. However, in all previous studies, these two factors were not manipulated independently. In this fMRI study, we could disentangle the two factors by using a different (two-digit) number stimulus set. Both behavioral and neurofunctional data suggest that the cognitive processes involved could be best explained by the (independent) factors target and distractor distance. Based on these data we suggest that the exact/approximate distinction does not seem to be as generally valid as previously assumed. We conclude that this study may be a starting point for a closer examination of the experimental, procedural and strategic conditions of when the exact/approximate distinction is valid and when it is not.


Endovascular Revascularization and Outcomes of Critical Limb-Threatening Ischemia in Trinidad and Tobago: The EVENT Pilot Study-Challenges in a Limited-Resource, Caribbean Setting.
This retrospective study investigated major adverse limb events (MALE) and mortality outcomes in critical limb-threatening ischemia (CLTI) patients with tissue loss after an endovascular revascularization-first (EVR-1st) strategy. MALE and mortality were assessed in 157 consecutive patients with CLTI and tissue loss from June 2019 to June 2022 at the Eric Williams Medical Sciences Complex, Trinidad and Tobago. 157 patients underwent the EVR-1st strategy, of whom 20 were pivoted to immediate surgical revascularization (SR). Of the remaining 137 patients, successful EVR was achieved in 112, giving a procedural success of 82% and an all-comer overall success of 71%. The mortality and MALE rates were 2.7% and 8.9% at 2 years, respectively. Males and patients with previous major amputations were at significantly higher risk for MALE (p values of 0.016 and 0.018, respectively). There was a statistically significant difference in successful EVR for both Rutherford-Baker (RB) 5 (minor) and RB 6 (major) classifications: 63 (56%) vs. 5 (20%) and 49 (44%) vs. 20 (80%), both with a p value of 0.01. There were no differences in successful EVR amongst Wound, Ischemia, Foot Infection (WIfI) clinical stages. There were no differences in successful EVR amongst the Trans-Atlantic Inter-Society Consensus (TASC II) classifications. This study may prove clinically informative and applicable for an EVR-1st management strategy for high-risk patients with CLTI in a limited-resource, Caribbean setting. NCT05547022 (retrospectively registered).


Weibull β value for the discernment of drug release mechanism of PLGA particles.
Mathematical models are used to characterize and optimize drug release in drug delivery systems (DDS). One of the most widely used DDS is the poly(lactic-co-glycolic acid) (PLGA)-based polymeric matrix owing to its biodegradability, biocompatibility, and easy manipulation of its properties through the manipulation of synthesis processes. Over the years, the Korsmeyer-Peppas model has been the most widely used model for characterizing the release profiles of PLGA DDS. However, owing to the limitations of the Korsmeyer-Peppas model, the Weibull model has emerged as an alternative for the characterization of the release profiles of PLGA polymeric matrices. The purpose of this study was to establish a correlation between the n and β parameters of the Korsmeyer-Peppas and Weibull models and to use the Weibull model to discern the drug release mechanism. A total of 451 datasets describing the overtime drug release of PLGA-based formulations from 173 scientific articles were fitted to both models. The Korsmeyer-Peppas model had a mean Akaike Information Criteria (AIC) value of 54.52 and an n value of 0.42, while the Weibull model had a mean AIC of 51.99 and a β value of 0.55, and by using reduced major axis regression values, a high correlation was found between the n and β values. These results demonstrate the ability of the Weibull model to characterize the release profiles of PLGA-based matrices and the usefulness of the β parameter for determining the drug release mechanism.


Effects of left ventricular venting and distention during heterogenous distribution of cardioplegic solution.
The effects of left ventricular venting and distention on myocardial protection during heterogenous distribution of cardioplegic solution remain undefined. This study was undertaken to determine if left ventricular venting enhances and distention impairs myocardial cooling and recovery of global and regional left ventricular function. Twenty-one pigs were placed on cardiopulmonary bypass and subjected to 80 minutes of ischemic arrest with the mid-left anterior descending artery occluded. Hearts were protected with multidose potassium (25 mEq/L) crystalloid cardioplegic solution supplemented with topical (4 degrees C) and systemic (28 degrees C) hypothermia. During arrest, the left ventricle was vented in seven pigs, seven pigs were not vented, and seven others had systemic pump blood infused into the left ventricle to maintain an end-diastolic pressure of 15 mm Hg. Parameters measured included left ventricular temperature, stroke work index, compliance (end-diastolic pressure-end-diastolic volume curves) and wall motion scores (two-dimensional echocardiography). Distended hearts had the lowest mean left ventricular temperature beyond the left anterior descending arterial occlusion (10.1 degrees +/- 1.8 degrees C distended [p less than 0.025 from vented and nonvented groups] versus 14.2 degrees +/- 0.7 degrees C vented versus 15.5 degrees +/- 1.2 degrees C nonvented), the highest postischemic stroke work index (0.78 +/- 0.09 gm-m/kg distended versus 0.62 +/- 0.07 gm-m/kg vented versus 0.66 +/- 0.07 gm-m/kg nonvented at end-diastolic pressure = 10 mm Hg), and the best wall motion scores (0.7 +/- 0.04 distended [p less than 0.025 from vented and nonvented groups] versus 5.5 +/- 1.80 vented versus 4.8 +/- 1.20 nonvented). Postischemic end-diastolic pressure-end-diastolic volume curves were unchanged from preischemic values in each group. We conclude that during heterogenous cardioplegic arrest, left ventricular venting offers no additional myocardial protection and may negate the beneficial effects of moderate (end-diastolic pressure = 15 mm Hg) left ventricular distention.


Transcriptional and biochemical analyses of Planomicrobium strain AX6 from Qinghai-Tibetan Plateau, China, reveal hydrogen peroxide scavenging potential.
The bacterial mechanisms responsible for hydrogen peroxide (H2O2) scavenging have been well-reported, yet little is known about how bacteria isolated from cold-environments respond to H2O2 stress. Therefore, we investigated the transcriptional profiling of the Planomicrobium strain AX6 strain isolated from the cold-desert ecosystem in the Qaidam Basin, Qinghai-Tibet Plateau, China, in response to H2O2 stress aiming to uncover the molecular mechanisms associated with H2O2 scavenging potential. We investigated the H2O2-scavenging potential of the bacterial Planomicrobium strain AX6 isolated from the cold-desert ecosystem in the Qaidam Basin, Qinghai-Tibet Plateau, China. Furthermore, we used high-throughput RNA-sequencing to unravel the molecular aspects associated with the H2O2 scavenging potential of the Planomicrobium strain AX6 isolate. In total, 3,427 differentially expressed genes (DEGs) were identified in Planomicrobium strain AX6 isolate in response to 4 h of H2O2 (1.5 mM) exposure. Besides, Kyoto Encyclopedia of Genes and Genomes pathway and Gene Ontology analyses revealed the down- and/or up-regulated pathways following H2O2 treatment. Our study not only identified the H2O2 scavenging capability of the strain nevertheless also a range of mechanisms to cope with the toxic effect of H2O2 through genes involved in oxidative stress response. Compared to control, several genes coding for antioxidant proteins, including glutathione peroxidase (GSH-Px), Coproporphyrinogen III oxidase, and superoxide dismutase (SOD), were relatively up-regulated in Planomicrobium strain AX6, when exposed to H2O2. Overall, the results suggest that the up-regulated genes responsible for antioxidant defense pathways serve as essential regulatory mechanisms for removing H2O2 in Planomicrobium strain AX6. The DEGs identified here could provide a competitive advantage for the existence of Planomicrobium strain AX6 in H2O2-polluted environments.


Central response to painful electrical esophageal stimulation in well-defined patients suffering from functional chest pain.
Functional chest pain (FCP) of presumed esophageal origin is considered a common cause for chest pain in which central nervous system hyperexcitability is thought to play an important role. We aimed to compare cerebral responses with painful esophageal stimuli between FCP patients and healthy subjects (HS). Thirteen patients with FCP (seven females, mean age 50.4 ± 7.5 years) and 15 HS (eight females, mean age 49.1 ± 12.9 years) were enrolled. Inclusion criteria consisted of typical chest pain, normal coronary angiogram, and normal upper gastrointestinal evaluation. Electrical stimulations evoking the pain threshold were applied in the distal esophagus, while cortical evoked potentials were recorded from the scalp. Pain scores, resting electroencephalogram (EEG), evoked potential characteristics and brain electrical sources to pain stimulation were compared between groups. No differences were seen between patients and HS regarding (i) pain thresholds (patients: 20.1 ± 7.4 mA vs HS: 22.4 ± 8.3 mA, all P > 0.05), (ii) resting-EEG (P > 0.05), (iii) evoked brain potential latencies (N2: patients 181.7 ± 25.7 mS vs HS 182.2 ± 25.8 mS, all P > 0.05) and amplitudes (N2P2: patients 8.2 ± 7.2 μV vs HS: 10.1 ± 3.4 μV, all P > 0.05), (iv) topography (P > 0.05), and (v) brain source location (P > 0.05). No differences in activation of brain areas to painful esophageal stimulation were seen in this group of well characterized patients with FCP compared with sex- and age-matched HS. The mechanism of pain in FCP and whether it originates in the esophagus remains unsolved.


Double-Row Rotator Cuff Repair Enhanced With Platelet-Rich Therapy Reduces Retear Rate: A Systematic Review and Meta-analysis of Randomized Controlled Trials.
To assess retear rates in arthroscopic double-row rotator cuff repair (double-row RCR) with and without platelet-rich therapy (PRT). Systematic review and meta-analysis of randomized controlled trials (RCTs). MEDLINE, Embase, and Scopus databases were searched for RCTs involving use of PRT exclusively in arthroscopic double-row RCR. A random-effects model and the generic inverse variance method were used for quantitative data synthesis. Heterogeneity was tested with the I2 statistic index. The 9 RCTs included in the meta-analysis demonstrated a risk reduction of 49% for retears in patients receiving PRT (risk ratio [RR] 0.51; 95% confidence interval [CI] 0.35 to 0.76; P = .0008; I2 = 0%). Divided by tear sizes, retear risk reduction of 47% (RR 0.53; 95% CI 0.30 to 0.95; P = .03; I2 = 0%) was found in small to medium tears and 51% (RR 0.49; 95% CI 0.29 to 0.84; P = .009; I2 = 0%) in large to massive tears. Linked double-row RCR resulted in risk reduction of 51% for retears in comparison with nonlinked repairs. Double-row RCR plus PRT significantly reduced retear rates in all sizes of rotator cuff tears. Linked double-row RCR and applying the PRT during the surgical procedure and in the tendon-bone interface reproduced the best outcomes. Clinically, all patients improved, and no statistically significant difference was seen in clinical and functional scores between the intervention groups. All patients achieved optimal values for patient-reported outcomes measures. I, systematic review and meta-analysis of level I studies.


Prevalence and antimicrobial resistance profiles of Campylobacter species in South Africa: a "One Health" approach using systematic review and meta-analysis.
This study investigated the prevalence and antibiotic resistance (AR) profiles of Campylobacter spp. isolated from animals, humans, and the environment in South Africa based on available published data. Original articles published from January 1, 1990 to January 1, 2021 were searched from PubMed, ScienceDirect, Google Scholar, Africa Index Medicus, Scopus, and African Journal Online databases. Data were analyzed with Comprehensive Meta-Analysis (version 3.0). After screening, articles on animals (n = 25), humans (n = 7), environment (n = 3), animals/environment (n = 2), and a (n = 1) study on animals, humans, and the environment were included in this review. The pooled prevalence estimates (PPEs) were 28.8%, 16.4%, and 28.4% in animals, humans, and the environment, respectively. The Campylobacter jejuni and Campylobacter coli species were commonly isolated from humans, animals, and the environment in South Africa. The AR profiles were screened from 2032 Campylobacter spp., with the highest PPE of AR observed against clindamycin (76.9%) and clarithromycin (76.5%). Campylobacter isolates tested with the disk diffusion assay and minimum inhibitory concentration methods recorded an overall AR prevalence of 35.3% and 37.1%, respectively, whereas multidrug resistance PPE was 35.3%. Regular surveillance of Campylobacter spp. prevalence and its antimicrobial resistance strains is recommended, as well as the formulation of a "One Health" approach for better management and control of Campylobacter spp. infection in South Africa.


The estimation of D-isocitric acid in urine using isocitrate dehydrogenase.
The amount of D-isocitric acid in urine has been estimated using the enzyme isocitrate dehydrogenase. The technique is rapid and easy to perform. Reproducibility of results was good and results from recovery experiments were excellent. The concentration range for early morning urine samples from normal adults was 0.08-0.65 mmol/l with a mean of 0.29 mmol/l.


Prolonged respiratory disorder predicts adverse prognosis in infants with end-stage kidney disease.
Among comorbidities, pulmonary hypoplasia (PH) is known as a significant risk factor for mortality in infants with end-stage kidney disease (ESKD). However, the final outcomes of infants with both ESKD and PH are still not well defined, as the diagnosis modality, and definition of PH severity remain ambiguous. Children initiating peritoneal dialysis during infancy from 1990 to 2015 were followed until death, date of last contact, or the end of 2015. We examined the long-term outcome of children with congenital pulmonary disorders by studying infants with prolonged respiratory disorders of greater than 28 days duration after birth and evaluated risk factors for mortality. Forty-six children were followed (median follow-up, 9.23 years), and classified as children without (n = 38; Group A) or with (n = 8; Group B) a prolonged respiratory disorder. Overall actuarial 5 year survival rate in this cohort was 79.5 %. The survival curve in Group B showed a significant decline compared with Group A. Prolonged respiratory disorder was significantly associated with mortality by multivariate analysis (hazard ratio, 8.32). Infants who initiate peritoneal dialysis complicated by prolonged respiratory disorders have increased adverse risk factors for mortality; therefore, withholding aggressive treatment should be considered.


Improved suture tying technique in microsurgery.
A technique is presented that maintains control of the short suture end in microsurgical suture tying. This technique significantly shortens the time taken to tie a microsurgical knot. It reduces the number of manoeuvres required to complete the knot and by maintaining control of the short suture end, prevents adherence to soft tissue.


Impact of Age and Sex on Subclinical Coronary Atherosclerosis in a Healthy Asian Population.
The influence of age and sex on clinical atherosclerotic cardiovascular disease is well reported, but literature remains sparse on whether these extend to the disease in its preclinical stage. The purpose of this study was to report the prevalence, risk factors, and impact of age and sex on the burden of subclinical coronary atherosclerosis in a healthy Asian population. Healthy subjects age 30 to 69 years, with no history of cardiovascular disease or diabetes were recruited from the general population. Subclinical coronary atherosclerosis was quantified via the coronary artery calcium score (CAC) with CAC of 0 indicating absence of calcified plaque, 1 to 10 minimal plaque, 11 to 100 mild plaque, and >100 moderate to severe plaque. A total of 663 individuals (mean age 49.4 ± 9.2 years; 44.8% men) were included. The prevalence of any CAC was 29.3%, with 9% having CAC >100. The prevalence was significantly higher in men than women (43.1% vs 18.0%; P < 0.001). Multivariable analysis revealed significant associations of increasing age, male sex, higher blood pressure, increased glucose levels, and higher low-density lipoprotein cholesterol levels with the presence of any CAC. Low-density lipoprotein cholesterol was more significantly associated with CAC in women compared with men (P interaction = 0.022). The prevalence of preclinical atherosclerosis increased with age, and was higher in men, with sex-specific differences in associated risk factors. These results will better inform individualized future risk management strategies to prevent the development and progression of coronary artery disease within healthy individuals.


Tryptophan metabolism and immunogenetics in major depression: a role for interferon-γ gene.
The tryptophan metabolism and immune activation play a role in pathophysiology of major depressive disorders. The pro-inflammatory cytokine interferon-γ transcriptionally induces the indoleamine 2,3-dioxygenase enzyme that degrades the tryptophan and thus induces serotonin depletion. The polymorphism of certain cytokine genes was reported to be associated with major depression. We investigated the association between interferon-γ (IFNγ) gene CA repeat polymorphism, the profile of serotonin and tryptophan pathway metabolites and clinical parameters in 125 depressed patients and 93 healthy controls. Compared to controls, serum tryptophan and 5-hydroxyindoleacetic acid (5HIAA) concentrations in the patients were significantly lower and serum kynurenine concentrations were significantly higher at baseline (p<0.0001). The presence of IFNγ CA repeat allele 2 homozygous has significant association with higher kynurenine concentrations in controls (F=4.47, p=0.038) as well as in patients (F=3.79, p=0.045). The existence of interferon-γ CA repeat allele 2 (homo- or heterozygous) showed significant association with increase of tryptophan breakdown over time during the study period (F=6.0, p=0.019). The results indicated the association between IFNγ CA repeat allele 2, tryptophan metabolism and the effect of medication.