Selected neurotoxins.
The small animal practitioner is faced with an infinite number of potential toxins in our modern environment. Unapproved usage of drugs and insecticides requires the practitioner to keep informed about the development of new toxic syndromes. Recreational drug toxicosis in animals is still seen with some frequency in clinical practice and should not be overlooked, even when the owner denies the possible exposure. In this article, we have discussed a few of the more common and newer neurotoxicities seen in clinical practice today. Neurologic toxicities are complex, but treatment can be rewarding if early diagnosis is made and aggressive therapy is instituted. The practitioner will find it worthwhile to establish contact with a toxicologist or poison information center for additional support when necessary.


Correction to: Developing real-world comparators for clinical trials in chemotherapy-refractory patients with gastric cancer or gastroesophageal junction cancer.
ping real-world comparators for.


Studies on the mechanism of the positive inotropic action evoked by epinine on the rabbit isolated papillary muscle at different rates of beating.
1. Effects of epinine on cyclic AMP and contractility were investigated in rabbit papillary muscles driven at a rate of 0.5 or 2.0 Hz. 2. When the frequency of stimulation was increased from 0.5 to 2.0 Hz, the log dose-response curve for the positive inotropic effect of epinine was displaced to the left, whereas the maximum of the developed tension was not changed. 3. At both frequencies phentolamine (1 mumol/l) shifted the lower part of the log dose-response curve for epinine to the right, whereas pindolol (30 nmol/l) affected mainly the upper part. In the presence of both alpha- and beta-adrenoceptor antagonists, the whole curve was shifted to the right in a parallel manner. However, cocaine (30 mumol/l) did not significantly influence the log dose-response curve of epinine. 4. At 0.5 Hz a submaximal effective concentration of epinine (100 mumol/l) led to an approximately 100% increase of the cyclic AMP level after 60s; the same increase of the cyclic AMP level was induced at 2.0 Hz by one-third the concentration of epinine (30 mumol/l). 5. Phentolamine (1 mumol/l) did not affect the increase of the cyclic AMP level evoked by epinine, whereas pindolol (30 nmol/l) completely depressed it. 6. The present results indicate that epinine produces its positive inotropic effect through direct stimulation of myocardial alpha-adrenoceptors as well as beta-adrenoceptors, depending upon the concentration: in lower concentrations it acts mainly on alpha-adrenoceptors, whereas in higher concentrations it acts predominantly on beta-adrenoceptors. The positive inotropic effect through beta-adrenoceptor stimulation is mediated by cyclic AMP, while that through alpha-adrenoceptors is not.


Pyridinium cationic-dimer antimalarials, unlike chloroquine, act selectively between the schizont stage and the ring stage of Plasmodium falciparum.
Malaria is a leading cause of death in developing countries, and the emergence of strains resistant to the main therapeutic agent, chloroquine, has become a serious problem. We have developed cationic-dimer type antimalarials, MAP-610 and PMAP-H10, which are structurally different from chloroquine. In this study, we introduced several substituents on the terminal phenyl rings of PMAP-H10. The electronic and hydrophobic properties of the substituents were correlated with the antimalarial activity and cytotoxicity of the compounds, respectively. Studies with synchronized cultures of malarial plasmodia showed that our cationic-dimers act selectively between the schizont stage and the ring stage of the parasitic cycle, unlike chloroquine, which has a stage-independent action. Thus, the mechanism of action of our antimalarials appears to be different from that of chloroquine, and our compounds may be effective against chloroquine-resistant strains.


Excision of apurinic and/or apyrimidinic sites from DNA by nucleolytical enzymes from rat brain.
Apurinic and/or apyrimidinic (AP) sites were excised from PM2 phage DNA by two enzymes: an AP endodeoxyribonuclease isolated from rat neocortex chromatin and a rat brain exodeoxyribonuclease, DNase B III. The resulting gap was filled with DNA polymerase beta prepared from rat liver and finally ligated by Escherichia coli DNA ligase.


Utility of parathyroid hormone immunocytochemistry in fine needle aspiration diagnosis of parathyroid tissue.
The cytomorphological features of parathyroid tissue (PTT) may overlap with those of thyroid lesions, thus posing a diagnostic challenge. In this retrospective study, we reviewed our institutional experience in using parathyroid hormone (PTH) immunocytochemistry (ICC) to substantiate the diagnosis of PTT on fine needle aspiration (FNA). Our pathology database was searched for FNA cases in which PTH ICC was performed between 1 January 2015 and 31 March 2022. PTH ICC was performed on a ThinPrep slide in cases with a clinical suspicion of PTT or with cytomorphological features raising the possibility of PTT. Patients' clinicopathological characteristics, PTH ICC results, cytological diagnoses, and surgical follow-ups, if available, were reviewed and analysed. The study cohort included 103 cases clinically designated as thyroid (n = 85, 82.5%), parathyroid (n = 11, 10.7%) and neck soft tissue (n = 7, 6.8%). PTH immunostaining was negative, positive, and indeterminate in 53 (51.5%), 27 (26.2%), and 23 (22.3%) cases, respectively. Surgical follow-up was available in 27 (26.2%) cases, including 17 thyroid lesions and 10 PTT cases. All positive PTH cases were confirmed to be PTT, while all but one of the negative PTH cases were non-PTT on follow-up. The calculated sensitivity, specificity, positive and negative predictive values were 85.7%, 100%, 100% and 93.3%, respectively. Our study demonstrates that PTH ICC performed on additional ThinPrep slides is a valuable adjunct test in FNA samples with a differential diagnosis of PTT vs non-PTT. Low cellularity may be a limiting factor in the accurate assessment of PTH by ICC.


Periprostatic nerve blockade before transrectal ultrasound-guided prostate biopsy: the Ankara Numune experience.
To assess the efficacy and morbidity of periprostatic local anesthesia before transrectal ultrasound-guided biopsy of the prostate. From August 2001 to December 2001, 58 patients underwent transrectal ultrasound-guided prostate biopsy at the 2nd Department of Urology, Ankara Numune Education and Research Hospital. Fifty patients who fulfilled the inclusion criteria were randomized into 2 groups of 25 patients each. Group 1 received periprostatic local anesthesia with 1% lidocaine while group 2 received no local anesthesia. Pain scale responses were analyzed for each aspect of the biopsy procedure with a visual analog scale. There was no difference between the 2 groups in pain scores during digital rectal examination, intramuscular injection and probe insertion. The mean pain scores during needle insertion in group 1 receiving periprostatic nerve block and in group 2 receiving no local anesthesia were 3.00 +/- 2.22 and 6.16 +/- 2.85, respectively, and were found to be significantly different (p < 0.001), but morbidity after the biopsy was not statistically different between the 2 groups. Periprostatic local anesthesia before prostate biopsy is a safe and easy method to increase patient comfort during the procedure.


Science in medicine: too much or too little and too limited in scope?
Contrary to the common assertion that there is too much science in medicine, it is precisely the application of the natural sciences in the clinic that has enhanced the diagnostic and therapeutic powers of the physician. Much of the criticism of science in medicine mistakes the technology made possible by science, and the way that technology is employed, for science itself. What has hampered progress is too narrow a view of the sciences relevant to medicine. The concepts and methods of the social sciences must be integrated into medical education if physicians are to be enabled to respond effectively to illness as a human experience. Nonetheless, without major changes in the social context of medical practice, efforts to improve performance through curriculum reform will be futile.


Explaining the lower usage rate of indigenous construction materials in Ghanaian public buildings using bounded rationality.
Judicious use of Indigenous Construction Materials (ICM) contributes to sustainability of a local construction industry. Why has the use of ICMs not contributed to the sustainability of the Ghanaian Construction Industry (GCI), and how can the use of ICMs engender the sustainability of GCI and that of similar developing countries? This paper uses bounded rationality and mixed-method strategy to explain the ICM usage rate in the GCI, and describes measures for improving the sustainability of the local construction industry through ICMs use. Relatively high ICM cost and non-availability of alternatives have been found as factors largely responsible for constrained ICMs usage. This paper is one of the first to draw on a synergy of the bounded rationality theory and empirical findings to give advanced insight into factors constraining the use of ICMs, as well as provide a measured usage rate of local building materials using real building projects cases. The research has carved a path for nurturing sustainable construction industry in developing countries through indigenous resources.


Comparison of age-based weight estimation with actual measured weight in children aged one to twelve years in Enugu.
This study was carried out to evaluate the degree of accuracy of age-based weight estimation methods in assessing the weight of the Nigerian child. The weights of one thousand, four hundred and fifty-six (1,456) children were measured and compared with the updated Advanced Paediatric Life Support (APLS), Best guess, Nelson and Luscombe & Owen methods. The updated APLS, Nelson and Luscombe & Owen methods underestimated the weights in younger children while overestimating in older ones. Best guess overestimated the weights across all ages. The Nelson formula had the best agreement within 10% and 20% of the measured weights among all methods. A linear regression analysis produced an equation for weight estimation: weight (W) = 2.058 Y + 9.925, where W is weight in kilogram and Y is the age in years. None of the weight estimation formulae assessed was entirely accurate in our study, though the Nelson method showed superior agreement.


Total rectal resection and colo-anal anastomosis for low rectal tumours: comparative results in a group of young and old patients.
Rectal cancer incidence is increasing among the elderly who are more often considered for palliation rather than for surgical cure. Moreover, sphincter-sparing surgery is often avoided when treating the elderly. We report our experience on a consecutive series of 38 subjects, suffering from a lower third rectal tumour with a median distance of 5.6 cm from the anal verge (7 Dukes' A, 6 Dukes' B, 17 Dukes' C, 3 Dukes' D, 3 anastomotic recurrences and 2 large villous adenomas). All subjects were prospectively collected in a 2-year period and treated with total resection and colo-anal hand-sewn anastomosis on a J colic reservoir. 20 patients younger than 65 years and 18 over 65 years were matched for surgical complications, late morbidity, oncological and functional results but no statistical difference was found. Our hope is that a conservative approach in treating the low rectal tumours will progressively be accepted for elderly patients.


Mobile Phone Use and The Risk of Headache: A Systematic Review and Meta-analysis of Cross-sectional Studies.
Headache is increasingly being reported as a detrimental effect of mobile phone (MP) use. However, studies aimed to investigate the association between MP use and headache yielded conflicting results. To assess the consistency of the data on the topic, we performed a systematic review and meta-analysis of the available cross-sectional studies. Published literature from PubMed and other databases were retrieved and screened, and 7 cross-sectional studies were finally included in this meta-analysis. The pooled odds ratio (OR) and 95% confidence interval (CI) were calculated. We found that the risk of headache was increased by 38% in MP user compared with non-MP user (OR, 1.38; 95% CI, 1.18-1.61, p < 0.001). Among MP users, the risk of headache was also increased in those who had longer daily call duration (2-15 min vs. <2 min: OR, 1.62; 95% CI, 1.34-1.98, p < 0.001; >15 min vs. <2 min: OR, 2.50; 95% CI, 1.76-3.54, p < 0.001) and higher daily call frequency (2-4 calls vs. <2 calls: OR, 1.37; 95% CI, 1.07-1.76, p < 0.001; >4 calls vs. <2 calls: OR, 2.52; 95% CI, 1.78-3.58, p < 0.001). Our data indicate that MP use is significantly associated with headache, further epidemiologic and experimental studies are required to affirm and understand this association.


Assessment of the difference in depressive symptoms of the Korean adult population before and during the COVID-19 pandemic using a community health survey.
The aim of this study was to evaluate the rate of depression during the COVID-19 pandemic compared to that during the prepandemic period. Data from participants in the Korean Community Health Survey in 2019 and 2020 aged ≥ 19 years old were analyzed. In total, the data of 223,306 participants from the 2020 group were compared with the data of 217,133 participants from the 2019 group regarding the experience and severity of depression. The experience of depression was surveyed in terms of a history of sadness or despair for ≥2 weeks in the last year. In addition, the PHQ-9 scores were used, and participants with PHQ-9 scores ≥10 were recategorized as having moderate to severe depression. The odds for depression of the 2020 group compared to the 2019 group based on the survey and PHQ-9 scores were calculated using simple or multiple logistic regression with complex sampling with weighted values. The rate of depression experience was lower in the 2020 group than in the 2019 group. The odds of experiencing depression were lower in the 2020 group than in the 2019 group (adjusted odds ratio [aOR] = 0.95, 95% confidence intervals [95% CI] = 0.91-0.98, P = 0.004). The odds of moderate to severe depression were also lower in the 2020 group than in the 2019 group (aOR=0.92, 95% CI=0.88-0.97, P = 0.001). The rate of depression experience was not higher during the COVID-19 pandemic than during the prepandemic period in Korea.


Lack of backscatter factor measurements in HDR applications with MOSkins.
Measurements of backscatter correction factors for intra operative (IOBT) HDR brachytherapy applicators were made using Centre for Medical Radiation Physics (CMRP), MOSFET devices. In clinical use there is an absence of backscatter material above the IOBT applicator, leading to a lower dose than predicted by conventional TG-43 dose calculations. To estimate the uncertainty in the MOSFET measurements, the dosimetric characteristics, including reproducibility, stability, linearity, and angular and energy response were measured using a HDR Ir-192 source, kilovoltage treatment unit and a high energy linac. Measurements were compared with previously published Monte Carlo data. Variability of the response of the MOSFETs due to angular variation contributed the largest uncertainty in dose measurements. Using the IOBT applicator without adequate scatter material resulted in a reduction of delivered dose of on average 10%, but was dependent on the location on the applicator and the treatment field size. Theoretical calculations based on previously published study indicated an expected reduced dose of on average 4%. MOSFET devices provide an ideal measurement tool in the presence of high dose gradients, however, the dosimetric characteristics of the detector must be accounted for when estimating the uncertainty.


Interobserver variability in physician-modified endograft planning by comparison with a three-dimensional printed aortic model.
With the increasing application of fenestrated and physician-modified endografting for aneurysm repair, there is increasing concern about the accuracy of vessel position measurements based on computed tomography scans. Inaccuracies in measurements may result in a "window-shutter" or "eclipsing" phenomenon whereby the fenestration may not overlie the vessel ostium completely. We hypothesized that vessel position measurements from reconstructed imaging do not represent the true vessel position as obtained from a three-dimensional (3D) printed physical model of the visceral aortic segment. Medical 3D modeling software was used to develop the 3D reconstructions, which were then exported to the 3D printing software. This allowed 3D models to be physically generated. The distances to the top and bottom and the angle of each of the celiac, superior mesenteric, right renal, and left renal arteries were recorded. These same measurements were obtained by each of the blinded reviewers in addition to the aortic diameter at the midpoint of each of these vessels. Measurements were compared with intraclass correlation coefficient, nonparametric Spearman rank correlation test, and one-sample t-test to assess accuracy and precision. Statistical significance was set at P < .05 for all tests. Both the individual measurements and the average of the measurements were statistically accurate (significant) for the bottom of the superior mesenteric artery and the top and bottom of both the right and left renal arteries. There was variability and inaccuracy in all visceral vessel angles and in the bottom of the celiac artery (the top and the angle of the celiac artery were the arbitrary referents). Whereas the visceral vessel orifices are largely accurately assessed and measured, the vessel angles are not. This may lead to an eclipsing phenomenon, which may contribute to branch or fenestrated vessel failure and therefore reintervention. Further efforts should assess the clinical significance of the eclipsing phenomenon and should target accurate and appropriate fenestration construction to prevent long-term morbidity.


Age-related patterns of cocaine and methamphetamine use across the life course in the United States: Disparities by gender and sexual identity among adults.
Research showing substance use decreases over the life course has focused primarily on heterosexual adults. We examined how age-related patterns of cocaine and methamphetamine use vary by sexual identity and gender among a national sample. We included 191,954 adults aged 18-64 from the 2015-2019 National Survey on Drug Use and Health. We described the weighted prevalence of past-year cocaine and methamphetamine use and used logistic regressions to estimate relative odds of past-year cocaine and methamphetamine use by age, stratified by gender and sexual identity (heterosexual, gay/lesbian, bisexual). Cocaine and methamphetamine use was highest among lesbian, gay, and bisexual (LGB) adults compared to their heterosexual counterparts. Gay/lesbian men and women and bisexual men were also more likely to use cocaine at later ages. Heterosexual adults ages 26-34 (adjusted odds ratio [aOR] = 0.73; confidence interval [CI] = 0.65-0.83) were less likely than those 21-25 to report past-year cocaine use, but there were no differences between those ages 26-34 and 21-25 among any LGB sub-group. Heterosexual (aOR = 1.62; CI = 1.28-2.04) and gay (aOR = 2.93; CI = 1.26-6.80), men ages 26-34 were more likely to report past-year methamphetamine use than their counterparts ages 21-25. There were no age-related differences in past-year methamphetamine use between bisexual men and gay/lesbian women. Patterns of cocaine and methamphetamine use across the life course for LGB individuals differ from those of heterosexuals. This has implications for targeted prevention efforts to address stimulant use among minoritized populations.


Species differences in the response of mammalian photoreceptor cyclic GMP and PIII to a reduction in calcium.
Changes in the content of cyclic GMP (cGMP), induced by exposure of isolated, dark-adapted mouse, cat and dog retinas to media depleted of calcium, have been compared with the amplitude of the trans-retinal PIII. Major differences exist in the time-course and magnitude of effects between the species and, in the cat and dog, changes in PIII (potentially a reflection of free cGMP in photoreceptor outer segments) do not correlate with those occurring in total cGMP. The observations imply species variation, not only in the enzymes maintaining cGMP homeostasis in photoreceptors, but also in phototransduction and allied processes.


The kinetics of heparin inhibition of the esterase and basal lipase activities of lipoprotein lipase.
The kinetics of inhibition of the esterase and lipase activities of bovine milk lipoprotein lipase (LPL) were compared. The esterase LPL activity against emulsified tributyrylglycerol was not affected by the enzyme activator apolipoprotein C-II (C-II) and amounted to about 15% of the "plus activator" lipase enzyme activity. Heparin at concentrations of 20 micrograms/ml inhibited 25% of the esterase activity. The reaction followed Henri-Michaelis-Menten kinetics and the inhibition by heparin followed a linear, intersecting, noncompetitive kinetic model. On the other hand, the basal lipase activity of LPL against emulsified trioleoylglycerol (TG) was very sensitive to inhibition by heparin: 1 microgram/ml inhibited about 80% of the reaction and 3 micrograms/ml drove the reaction to zero. The velocity curve for the uninhibited basal LPL activity was sigmoidal with an apparent nH(TG) of 2.94. Heparin inhibited the lipase activity competitively: heparin decreased nH(TG) and increased[TG]0.5 6.4-fold, while TG decreased the nH(Heparin) from 2.14 to 0.95 and caused a 3-fold increase in [Heparin]0.5. C-II, at concentrations lower than 2.5 X 10(-8) M (i.e., lower than KA), countered the inhibitory effects of heparin: at constant inhibitor concentrations, C-II increased nH(TG) from 1.78 to 2.52 and decreased [TG]0.5 about 10-fold; it also increased the apparent Vmax. At the lower C-II concentrations, nH(C-II) was approximately equal to 1.0 and increasing the TG concentrations decreased [C-II]0.5 from 3.8 X 10(-8) to 8.5 X 10(-9) M, with no effect on the nH(C-II). At the higher C-II concentrations, nH(C-II) was 2.5 and TG decreased [C-II]0.5 about 2-fold with no effect on the nH(C-II). In the absence of heparin, C-II had no effect on nH(TG) nor on [TG]0.5, but it increased the apparent Vmax. On the other hand, TG had no effect on nH(C-II) nor on [C-II]0.5, but at any given C-II concentration, the reaction velocity increased with increasing TG concentrations. It is concluded that TG and heparin as well as C-II and heparin are mutually exclusive and that lipoprotein lipase is a multisite enzyme, possibly a tetramer, with three high-affinity catalytic sites, and an equal number of sites for C-II and heparin per oligomer. However, LPL differs from classical allosteric enzymes in that its activator has no effect on substrate cooperativity nor on [S]0.5; its only effect is to increase Vmax by increasing the catalytic rate constant kp by inducing conformational changes in the enzyme.


Occlusive retinal vasculitis in a patient with West Nile virus.
West Nile virus (WNV) was first identified in the United States in 1999. In addition to a spectrum of systemic manifestations, several ocular conditions secondary to the virus have been reported, including chorioretinitis, uveitis and optic neuritis. Age and diabetes mellitus (DM) have been reported to be associated risk factors for the more severe forms of the systemic disease. Only seven cases of occlusive retinal vasculitis have been reported in patients with WNV infection. A 60-year-old Asian male presented with complaints of decreased vision in his left eye. He had been hospitalised approximately seven weeks earlier with meningo-encephalitis secondary to presumed WNV infection, at which time he was also diagnosed with DM. The visual loss coincided with the manifestation of systemic WNV infection. Old peripheral chorioretinal lesions without active inflammation in both eyes were consistent with WNV infection. In addition, retinal haemorrhage and cotton wool spots were noted in the posterior pole of both eyes with severe macular ischaemia in the left eye. Occlusive retinal vasculitis is an uncommon ocular manifestation of WNV, which should be suspected in patients with meningitis or encephalitis who reside in endemic areas with ocular findings of the disease.


Role of GO and r-GO in resistance switching behavior of bilayer TiO2 based RRAM.
Graphene-based resistance random access memory devices (RRAMs) have shown promise as a suitable replacement for flash memories, owing to their fast switching speed, low programming voltage, better scalability and great reliability. Furthermore, recent research works have shown bi-layer RRAM devices exhibiting better performance along the same parameters, where titania is one of the most commonly used materials. In the present work, we have studied the resistance switching behavior in a bi-layer RRAM device structure of TiO2 with graphene oxide (GO) and reduced graphene oxide (rGO). Switching mechanism in these devices has been investigated by detailed experimental characterization in conjunction with a finite element modeling (FEM) simulation. A dual conical conductive filament has been used in the present work, based on the modeling of the electroforming process carried out by FEM. It has been demonstrated that for the GO/TiO2 based hybrid RRAM device structure, GO acts as an active filament formation layer, whereas in the rGO/TiO2 bi-layer structure, rGO acts as a mere electrode.


Characteristics and experience of the patient in psychotherapy and the psychotherapy's effectiveness. A structural approach.
The study concerns the relationship between three groups of variables presenting the patient's perspective: (1) "patient's characteristics" before psychotherapy, including "expectations of the therapy"; (2) "experience in the therapy", including the "psychotherapeutic relationship"; and (3) "assessment of the direct effectiveness of the psychotherapy". Data from the literature are the basis for predicting relationships between all of these variables. Measurement of the variables was conducted using a follow-up survey. The survey was sent to a total of 1,210 former patients of the Academic Center for Psychotherapy (AOP) in which the therapy is conducted mainly with the students and employees of the University of Warsaw. Responses were received from 276 people. 55% of the respondents were women and 45% were men, under 30 years of age. The analyses were performed using structural equations. Two models emerged from an analysis of the relationship between the three above-mentioned groups of variables. One concerns the relationship between (1) the patient's characteristics (2) the course of psychotherapy, in which -from the perspective of the patient - there is a good relationship with the psychotherapist and (3) psychotherapy is effective. The second model refers to (2) the patient's experience of poor psychotherapeutic relationship and (3) ineffective psychotherapy. Patient's expectations of the psychotherapy (especially "the expectation of support") proved to be important moderating variablesin the models-among the characteristics of the patient. The mathematical model also revealed strong correlation of variables measuring "the relationship with the psychotherapist" and "therapeutic interventions".


Feasibility and stability in large Lotka Volterra systems with interaction structure.
Complex system stability can be studied via linear stability analysis using random matrix theory (RMT) or via feasibility (requiring positive equilibrium abundances). Both approaches highlight the importance of interaction structure. Here we show, analytically and numerically, how RMT and feasibility approaches can be complementary. In generalized Lotka-Volterra (GLV) models with random interaction matrices, feasibility increases when predator-prey interactions increase; increasing competition/mutualism has the opposite effect. These changes have crucial impact on the stability of the GLV model.


Aberrant signaling in the TNFalpha/TNF receptor 1 pathway of the NZM2410 lupus-prone mouse.
The purpose of this study was to evaluate the ability to induce TNFalpha-dependent apoptosis in vivo in predisease lupus-prone NZM2410 and derived B6.NZM congenic mouse strains. An endotoxicosis model that utilizes LPS and d-galactosamine to induce mortality by TNFalpha/TNFR1-dependent hepatocyte apoptosis was used to assess TNFalpha production, apoptotic signaling, and effects on the production of IL-6 and IL-10. NZM2410 was found to be resistant to endotoxicosis and to produce significantly less TNFalpha-induced IL-6 and IL-10. At low doses of LPS, partial resistance was associated with the Tnfa(w) allele. At higher doses of LPS, partial resistance cosegregated with lupus-susceptibility loci and functionally mapped downstream of caspase 3. Additional partial resistance in NZM2410 was also found upstream of FADD. These results demonstrate the existence of multiple defects in the TNFalpha/TNFR1 signaling pathway in the NZM2410 mouse and their relevance to lupus pathogenesis is discussed.


[Risk of cancer in patients following chronic dialysis and kidney graft].
A high prevalence of renal insufficiency has been observed in cancer patients as well as a high incidence of de novo cancer in dialysis or renal transplant patients. We aimed to determine the incidence of cancer in patients under dialysis and in kidney transplant recipients through a search of the literature. Under chronic dialysis, the risk of cancer increases from 1.1 to 1.8 in comparison to the general population. These risks reach 2.5 to 3.9 in renal transplant patients, but depend on the type of tumor. In transplant recipients, the risk of cancer induced by immunosuppressive therapy requires a specific follow-up and a screening for any medical history of cancer in the donor and the recipient.


Experimental infection of aquatic bird bornavirus 1 in domestic chickens.
Aquatic bird bornavirus 1 (ABBV-1), classified in the Orthobornavirus genus, is a neurotropic virus that infects wild waterfowl causing persistent infection of the nervous system. Given the conspicuous presence of wild waterfowl in urban areas and farmlands, spillover of this virus into domesticated poultry species is a concern. The goal of this study was to test the ability of ABBV-1 to infect and cause disease in chickens. Two day-old, White Leghorn chickens (n, 176) were inoculated with ABBV-1 through the oral, intramuscular, or intracranial routes, and sampled at 1, 4, 8, and 12-weeks post infection (wpi) to assess virus replication and lesion development. Chickens became infected only through the intracranial and intramuscular routes, developing earliest infection in the brain by 1 wpi (intracranial group), and spinal cord by 8 wpi (intramuscular group). Except for the kidney of one bird in the intracranial group, no other tissues (including choanal and cloacal swabs) tested positive for the virus. Therefore, while the virus could reach the central nervous tissue (CNS) from the muscle in approximately 20% of birds (centripetal spread), it inefficiently reached peripheral sites after replication in the CNS (centrifugal spread). Inflammation in the CNS was observed in the intracranial and intramuscular groups starting at 8 and 12 wpi, respectively, and consisted of mononuclear perivascular cuffing. This is the first study to document the susceptibility of chickens to ABBV-1 infection, and indicates that this species can become infected with ABBV-1, although less extensively than what is observed in waterfowl. This suggests that ABBV-1 replication is partially restricted in gallinaceous birds.


Experience with pyeloureterostomy associated with simple ligation of native ureter without ipsilateral nephrectomy in renal transplantation.
Ureteroneocystostomy was used as the primary method of urinary tract reconstruction in 282 allograft renal transplants at our center since 1965. A nonrefluxing anastomosis was incorporated whenever possible. Seven patients who suffered major urological complications involving the ureteroneocystostomy required pyeloureterostomy as the method of repair using the patient's distal native ureter. No ipsilateral nephrectomy was performed and simple ligation of the native ureter with nonabsorbable suture was accomplished. Of the 7 patients 3 suffered hydronephrosis of the native kidney. None of these patients had signs or symptoms secondary to acute and chronic ureteral occlusion. Our experience suggests that intentional ligation of the native ureter during pyeloureterostomy does not result in increased morbidity to the transplant patient, and that the need for ipsilateral nephrectomy with its own added morbidity may not be necessary.


Decreasing the Cerebral Edema Associated with Traumatic Intracerebral Hemorrhages: Use of a Minimally Invasive Technique.
Traumatic brain injury (TBI) is a major public health problem worldwide that affects all age groups. In the United States alone, there are approximately 50,000 deaths from severe traumatic brain injuries each year. In most studies, about 40 % of severe TBI have associated traumatic intracerebral hemorrhages (tICHs). The surgical treatment of tICH is debated largely because of its invasive nature, particularly in reaching deep tICHs. tICHs have a clear contribution to mass effect and exacerbate cerebral edema and ICP because of the break-down products of hemorrhage. We introduce a modification of the Mi SPACE technique (Minimally Invasive Subcortical Parafascicular Transsulcal Access for Clot Evacuation) that is applicable to tICH. In brief, this technique utilizes a trans-sulcal, stereotactic-guided technique in which a specially designed cannula is used to introduce a 13.5-mm-diameter tube into the epicenter of the tICH. We identified eight tICHs that were treated entirely or in part with the modified Mi SPACE technique during the time period from August 15, 2014 to December 15, 2014. This modified technique was readily deployed safely and efficaciously with significant removal of the tICH as demonstrated by postoperative CT scans. The removal of tICH using this minimally invasive technique may help with the control of ICP and cerebral edema.


Anti-arthritic and immunosuppressive activities of substituted triterpenoidal candidates.
We herein report the anti-arthritic and immunosuppressive activities of some synthesized substituted terpenoidal structure. Forty-four triterpenoid derivatives 1-21 containing a carboxylic, ester, amide and ketone groups attached to a triterpene moiety were conveniently synthesized and screened for their anti-arthritic and immunosuppressive activities. Synthetic triterpenoidal structures linked to a different function groups seem to be a promising approach in the search for novel leads for potent anti-arthritic and immunosuppressive agents. The detailed synthetic pathways of obtained compounds and anti-arthritic and immunosuppressive activities were reported.


Neurological deterioration as a potential alternative endpoint in human clinical trials of experimental pharmacological agents for treatment of severe traumatic brain injuries. Executive Committee of the International Selfotel Trial.
A recently improved understanding of the pathophysiological features of head injuries has led to the development of new drug therapies. Accurate human clinical trials remain necessary to document the efficacy and safety of new agents. It would be helpful to decrease the time from drug development to clinical use and general availability for drugs found to be effective. Conversely, ineffective agents could be abandoned in a timely fashion. A new endpoint measure, defined as neuroworsening (NW), is an objective observable event that is identifiable during hospitalization. This may enable the efficacy of drugs to be demonstrated or disproved much earlier than with 6-month outcome assessments. The prospective, double-blind, multicenter trial of the N-methyl-D-aspartate receptor antagonist Selfotel was used to acquire data on the efficacy of NW in predicting neurological outcomes. The 6-month Glasgow Outcome Scale scores, which were the primary endpoints of that trial, were compared with the frequency of NW. NW was an observable event that could be objectively defined after head injuries. Patients who suffered one or more episodes of NW demonstrated significantly higher morbidity and mortality rates than did patients who did not. Future trials should consider the use of NW as an outcome measure that can be included with more traditional measures in the study design. If the strong correlation demonstrated between NW and 6-month Glasgow Outcome Scale scores can be prospectively demonstrated in a successful trial, the time to approval of future agents could be decreased.


Ethical issues of placebo-controlled studies in depression and a randomized withdrawal trial in Japan: case study in the ethics of mental health research.
The use of placebo controls in psychiatric research is controversial. In this article, we focus on a troubling Japanese case of a randomized withdrawal trial of the antidepressant sertraline and analyze the ethical issues underlying it. First, we consider whether a placebo-controlled withdrawal trial should, in general, be considered more ethical than a standard placebo-controlled trial. We argue that the use of a placebo arm in this trial is ethically permissible but that there is no good reason to use a withdrawal trial design. Second, we discuss whether our moral evaluation of the use of placebo in this case should change when the special Japanese regulatory environment is taken into account. We argue that it should not and conclude that the use of withdrawal design in this case is ethically unacceptable.


Impact of weight loss induced by gastric bypass or caloric restriction on oxidative stress and genomic damage in obese Zucker rats.
Evidence on bariatric surgery induced weight loss and its possible impact on cancer risk is limited, but also controversial. We used obese Zucker(fa/fa) and lean Zucker(fa/+) to investigate the association between obesity, oxidative stress and genomic damage after weight loss induced either by Roux-en-Y gastric bypass surgery (RYGB) or caloric restriction. Male Zucker(fa/fa) rats underwent RYGB (n=15) or sham surgery (n=17). Five shams were food restricted and body weight matched (BWM) to RYGB. Twelve Zucker(fa/+) rats served as lean controls. Body weight and food intake were measured daily. An oral glucose tolerance test was performed on day 27. DHE staining and western blots of HSP70 and HO-1 were used to evaluate oxidative stress and anti-3-nitrotyrosine antibody staining for nitrative stress detection in colon and kidney. Lipid peroxidation products in urine were quantified by TBARS assay. LC/MS/MS was applied to measure urinary excretion of 8-oxoGua (oxidized DNA derived base), 8-oxodG (oxidized DNA derived nucleoside) and 8-oxoGuo (oxidized RNA derived nucleoside). DNA double strand breaks (DSBs) and cell proliferation (PCNA) were detected by immunohistochemistry. Sham-operated rats showed impaired glucose tolerance, elevated plasma insulin levels as well as elevated oxidative stress and nitrative stress markers, which were less severe after weight loss by RYGB or caloric restriction. Cell proliferation showed similar trends but no significant alteration. DNA DSBs were more frequent in sham-operated compared to all other groups. DNA damage in Zucker(fa/fa) rats positively correlated with basal plasma insulin values (Spearman's correlation coefficient for colon, 0.634 and for kidney, 0.525). RYGB and caloric restriction were sufficient to significantly reduce elevated oxidative/nitrative stress and genomic damage in obese Zucker(fa/fa) rats. Further investigations are needed to elucidate the underlying mechanism of these genome protective effects.


Rules embedded harris hawks optimizer for large-scale optimization problems.
Harris Hawks Optimizer (HHO) is a recent optimizer that was successfully applied for various real-world problems. However, working under large-scale problems requires an efficient exploration/exploitation balancing scheme that helps HHO to escape from possible local optima stagnation. To achieve this objective and boost the search efficiency of HHO, this study develops embedded rules used to make adaptive switching between exploration/exploitation based on search performances. These embedded rules were formulated based on several parameters such as population status, success rate, and the number of consumed search iterations. To verify the effectiveness of these embedded rules in improving HHO performances, a total of six standard high-dimensional functions ranging from 1000-D to 10,000-D and CEC'2010 large-scale benchmark were employed in this study. In addition, the proposed Rules Embedded Harris Hawks Optimizer (REHHO) applied for one real-world high dimensional wavelength selection problem. Conducted experiments showed that these embedded rules significantly improve HHO in terms of accuracy and convergence curve. In particular, REHHO was able to achieve superior performances against HHO in all conducted benchmark problems. Besides that, results showed that faster convergence was obtained from the embedded rules. Furthermore, REHHO was able to outperform several recent and state-of-the-art optimization algorithms.


Refined three-dimensional structure of phycoerythrocyanin from the cyanobacterium Mastigocladus laminosus at 2.7 A.
The structure of the phycobiliprotein phycoerythrocyanin from the thermophilic cyanobacterium Mastigocladus laminosus has been determined at 2.7 A resolution by X-ray diffraction methods on the basis of the molecular model of C-phycocyanin from the same organism. Hexagonal phycoerythrocyanin crystals of space group P6(3) with cell constants a = b = 156.86 A, c = 40.39 A, alpha = beta = 90 degrees, gamma = 120 degrees are almost isomorphous to C-phycocyanin crystals. The crystal structure has been refined by energy-restrained crystallographic refinement and model building. The conventional crystallographic R-factor of the final model was 19.2% with data to 2.7 A resolution. In phycoerythrocyanin, the three (alpha beta)-subunits are arranged around a 3-fold symmetry axis, as in C-phycocyanin. The two structures are very similar. After superposition, the 162 C alpha atoms of the alpha-subunit have a mean difference of 0.71 A and the 171 C alpha atoms of the beta-subunit differ by 0.51 A. The stereochemistry of the chiral atoms in the phycobiliviolin chromophore A84 is C(31)-R, C(4)-S. The configuration of the chromophore is C(10)-Z, C(15)-Z and the conformation C(5)-anti, C(9)-syn and C(14)-anti like the phycocyanobilin chromophores in phycoerythrocyanin and C-phycocyanin.


Current Status of Chemoprevention in Barrett's Esophagus.
Candidates for chemoprevention in Barrett's esophagus have long been suggested and there has been observational data to support many drugs, including statins, hormone replacement therapy, metformin, proton pump inhibitor therapy, and aspirin. Proton pump inhibitor therapy and aspirin are the most promising agents. Data suggest that aspirin and proton pump inhibitor therapy can decrease the risk of neoplastic progression in Barrett's esophagus. Further, the combination of aspirin and proton pump inhibitor therapy decrease all-cause mortality by approximately 33%. Future guideline groups need to evaluate the evidence rigorously, but the combination of proton pump inhibitor therapy and aspirin is promising.


Pd/C as a reusable catalyst for the coupling reaction of halophenols and arylboronic acids in aqueous media.
Pd/C was found to catalyze the Suzuki-Miyaura coupling reaction of halophenols in aqueous media. When halophenols were treated with ArB(OH)(2) and a catalytic amount of 10% Pd/C (0.3 mol % Pd) in aqueous K(2)CO(3) solution, the corresponding hydroxybiaryls were obtained in a high yield or quantitatively. The palladium catalyst was easily recovered and reused.


virtX - evaluation of a computer-based training system for mobile C-arm systems in trauma and orthopedic surgery.
Operating room personnel (ORP) operating mobile image intensifier systems (C-arms) need training to produce high quality radiographs with a minimum of time and X-ray exposure. Our study aims at evaluating acceptance, usability and learning effect of the CBT system virtX that simulates C-arm based X-ray imaging in the context of surgical case scenarios. Prospective, interventional study conducted during an ORP course with three groups: intervention group 1 (training on a PC using virtX), and 2 (virtX with a C-arm as input device), and a control group (training without virtX) - IV1, IV2 and CG. All participants finished training with the same exercise. Time needed to produce an image of sufficient quality was recorded and analyzed using One-Way-ANOVA and Dunnett post hoc test (alpha = .05). Acceptance and usability of virtX have been evaluated using a questionnaire. CG members (n = 21) needed more time for the exercise than those of IV2 (n = 20): 133 +/- 55 vs. 101 +/- 37 sec. (p = .03). IV1 (n = 12) also performed better than CG (128 +/- 48 sec.), but this was not statistically significant. Seventy-nine participants returned a questionnaire (81% female, age 34 +/- 9 years, professional experience 8.3 +/- 7.6 years; 77% regularly used a C-arm). 83% considered virtX a useful addition to conventional C-arm training. 91% assessed virtual radiography as helpful for understanding C-arm operation. Trainees experienced virtX as substantial enhancement of C-arm training. Training with virtX can reduce the time needed to perform an imaging task.


Study of constancy of hydrogen-consuming flora of human colon.
The constancy of the hydrogen consuming flora of the human colon was studied in 15 healthy subjects via two measurements obtained 18 to 36 months apart. Hydrogen disappearance rate and the major products of H2-consuming bacteria, methane and sulfide, were measured during incubation of fecal homogenates with excess hydrogen and sulfate. In 11/15, the hydrogen consumption rate and the predominant hydrogen-consuming pathway (methanogenesis, sulfate reduction, or neither) remained constant. However, major shifts in these pathways were observed in four subjects, with two losing and two gaining the ability to produce methane. Methanogenesis was associated with the highest hydrogen consumption rate. This study demonstrates that clinically unrecognizable, major alterations of the colonic flora occur in healthy subjects. Understanding of the factors responsible for these alterations might allow for therapeutic manipulation of the colonic flora.


Expression of glutamate receptors on cultured cerebral endothelial cells.
Activation of glutamate receptors has been shown to mediate a large number of neuronal processes such as long-term potentiation and ischemic damage. In addition to neurons and glia, glutamate receptors may occur on cerebral endothelial cells (CECs). The aim of the present study was to determine which glutamate receptors are expressed in CECs and to demonstrate the functional presence of such channels. By using reverse transcriptase-polymerase chain reaction, we showed that primary cultures of rat CECs express N-methyl-D-aspartate (NMDA) receptors (NR1 subunit, which is necessary for the formation of functional NMDA receptors, and NR2A-C subunits), 2-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl-propionate (AMPA) receptors (GLUR1-4 subunits), and metabotropic receptors (mGLUR). Exposure of the cultures to 2 mM glutamate, a well-established mediator of ischemic damage, for 30 min increased significantly the phosphorylation of calcium/calmodulin-dependent protein kinase II even after 10- and 60-min recovery times. This effect could be prevented by the NMDA blocker MK-801. The presence of multiple glutamate receptor types may confer a finely tuned responsiveness of the cerebral endothelium to glutamate in physiological and pathological conditions.


Quality of Life and Functional Mobility After Progressive Resistance Exercise in an Adolescent With a Liver Transplant.
This case report describes physical therapy intervention using progressive resistance exercise (PRE) with the recipient of a liver transplant to improve physical fitness, quality of life, and functional mobility. Outpatient physical therapy intervention included 2 phases, 10 weeks each, focused on functional training and PRE-based power training and functional tasks. Secondary conditions included excessive weight gain, adjustment disorder, and intensive scarring. PRE-based power training appears to be effective in an adolescent with decreased strength and endurance following liver transplant. Improvements in 1 repetition maximum, functional mobility, aerobic/anaerobic fitness, patient-directed goals, and quality of life were measurable. A PRE-based program may be useful in physical therapy with adolescents after liver transplant. Choice of musculature for training should be relevant to functional limitations and dosing of exercises must be sufficient for muscular hypertrophy.


Stromal Endocrine Cell Micronests Associated With an Ovarian Mucinous Cystadenoma: Endocrine Cell Preservation (Pseudohyperplasia) Potentially Mimicking Stromal Sex Cord Proliferation or Tumor Microinvasion.
Endocrine cell micronests (ECMs) have been described only twice previously in the ovary, both in association with mucinous neoplasms exhibiting intraepithelial endocrine cell hyperplasia. We report a 31-yr-old patient with a mucinous cystadenoma in which ECMs were distributed in the stroma surrounding degenerate glandular elements. Immunohistochemistry demonstrated only sparse endocrine cells within the neoplastic glands. We postulate that the ECMs in this case reflected relative preservation of endocrine elements in the context of epithelial atrophy, a process more commonly encountered in gastrointestinal pathology. Ovarian ECMs should also be distinguished from stromal sex cord proliferations and tumor microinvasion.


Paradoxical effects of mutant ubiquitin on Aβ plaque formation in an Alzheimer mouse model.
Amyloid-β (Aβ) plaques are a prominent pathological hallmark of Alzheimer's disease (AD). They consist of aggregated Aβ peptides, which are generated through sequential proteolytic processing of the transmembrane protein amyloid precursor protein (APP) and several Aβ-associated factors. Efficient clearance of Aβ from the brain is thought to be important to prevent the development and progression of AD. The ubiquitin-proteasome system (UPS) is one of the major pathways for protein breakdown in cells and it has been suggested that impaired UPS-mediated removal of protein aggregates could play an important role in the pathogenesis of AD. To study the effects of an impaired UPS on Aβ pathology in vivo, transgenic APPSwe/PS1ΔE9 mice (APPPS1) were crossed with transgenic mice expressing mutant ubiquitin (UBB+1), a protein-based inhibitor of the UPS. Surprisingly, the APPPS1/UBB+1 crossbreed showed a remarkable decrease in Aβ plaque load during aging. Further analysis showed that UBB+1 expression transiently restored PS1-NTF expression and γ-secretase activity in APPPS1 mice. Concurrently, UBB+1 decreased levels of β-APP-CTF, which is a γ-secretase substrate. Although UBB+1 reduced Aβ pathology in APPPS1 mice, it did not improve the behavioral deficits in these animals.


Magnetic resonance imaging in Duchenne muscular dystrophy: longitudinal assessment of natural history over 18 months.
In Duchenne muscular dystrophy (DMD), fat replacement of muscle may be a useful endpoint in trials of therapy, although progression in different muscle groups is uneven. In this study we assessed the progression of fat replacement with T(1) -weighted imaging over 2 9-month periods. Eight ambulant, corticosteroid-treated boys with DMD were imaged at 3 Tesla at 3 time-points (baseline and 9 and 18 months) with T(1) -weighted imaging to measure fat replacement. The greatest increase in fat content was measured in the biceps femoris long head, vastus lateralis, and rectus femoris, whereas the biceps femoris short head and gluteus maximus progressed more slowly. None of the lower leg muscles studied changed significantly. MRI can measure specific changes in fat replacement of muscle over time, demonstrating the variability in rates of natural progression between muscle groups and identifying those muscles suitable for use as biomarkers in clinical trials.


Canalicular Incisional Approach for Recanalization of Punctum: A Modified Surgical Treatment for Acquired Complete Upper and Lower Punctum Occlusions as an Alternative to Bypass Methods.
To define the success of surgical technique used in the treatment of epiphora that is caused by bi-canalicular acquired complete punctum occlusion. The study is a retrospective consecutive case series, who underwent canalicular incisional approach for recanalization (CIAFOR) for acquired bi-canalicular punctum occlusions. The authors have used this technique in the cases not possible to perform a punctum dilatation and not possible to determine the punctum location exactly due to severe fibrosis. Functional and anatomical success was evaluated by the absence of epiphora and with lavage at post-operative 6th months. Seven eyes of 5 patients (3 males and 2 females) were included in the study. The ages of the patients were 70, 65, 45, 64, and 70 years, respectively. Current follow-up periods vary between 6 and 23 months. Although functional and anatomical success achieved in all eyes, complication such as accessory punctum observed. CIAFOR seems to be a successful and simple surgical technique to treat acquired total punctum occlusion.


Computer-based inquiry to enhance science process skills in undergraduate students using physiological data.
The analysis of spontaneous tail coiling (STC) in zebrafish embryos is a functional parameter that allows the study of motor development. It has recently gained relevance as a biomarker to assess the neurotoxicity of environmental substances. Its practicability in the laboratory makes it an excellent pedagogical tool for promoting students' inquiry skills. However, the time and cost of materials and facilities limit their usage in undergraduate laboratories. This study presents the design of a computer-based educational module called ZebraSTMe, which is based on a tail coiling assay and aims to improve science process skills in undergraduate students by connecting them to relevant and novel content. We evaluate students' perception of learning, the quality of materials used, and the knowledge gained. Our results show that students perceived an improvement in their statistical analysis, representation, and discussion of experimental data. Additionally, the students evaluated the quality and ease of use of the materials and provided feedback for revision. A thematic analysis of the opinions revealed that the module activities promoted students' reflection on their professional strengths and weaknesses.NEW & NOTEWORTHY ZebraSTMe is a novel computer-based educational module that utilizes spontaneous tail coiling analysis in zebrafish embryos to enhance undergraduate students' scientific inquiry skills. By addressing the challenges of time, cost, and laboratory resources, the module improves students' science process skills and promotes reflection on their professional strengths and weaknesses. The innovative ZebraSTMe exemplifies the potential of integrating cutting-edge research topics into undergraduate education, leading to more engaging and effective learning experiences in physiology and other scientific disciplines.


RanGTP mediates nuclear pore complex assembly.
In metazoa, the nuclear envelope breaks down and reforms during each cell cycle. Nuclear pore complexes (NPCs), which serve as channels for transport between the nucleus and cytoplasm, assemble into the reforming nuclear envelope in a sequential process involving association of a subset of NPC proteins, nucleoporins, with chromatin followed by the formation of a closed nuclear envelope fenestrated by NPCs. How chromatin recruitment of nucleoporins and NPC assembly are regulated is unknown. Here we demonstrate that RanGTP production is required to dissociate nucleoporins Nup107, Nup153 and Nup358 from Importin beta, to target them to chromatin and to induce association between separate NPC subcomplexes. Additionally, either an excess of RanGTP or removal of Importin beta induces formation of NPC-containing membrane structures--annulate lamellae--both in vitro in the absence of chromatin and in vivo. Annulate lamellae formation is strongly and specifically inhibited by an excess of Importin beta. The data demonstrate that RanGTP triggers distinct steps of NPC assembly, and suggest a mechanism for the spatial restriction of NPC assembly to the surface of chromatin.


1,25-Dihydroxyvitamin D3 and 1,24-dihydroxyvitamin D3 suppress in vitro antibody response to T cell-dependent antigen.
1,25-Dihydroxyvitamin D3 and 1,24-dihydroxyvitamin D3 suppressed an antibody response to sheep red blood cells (SRBC, T cell-dependent antigen) by murine splenocytes, in concentrations ranging from 10(-10)-10(-7)M. These suppressive effects were markedly abrogated when T cell-depleted lymphocytes were cultured in the presence of a supernatant of concanavalin A-stimulated spleen cells. On the contrary, neither of them suppressed antibody response to trinitrophenyl-lipopolysaccharide (T cell-independent antigen). These results suggest that the suppressive effect of active vitamin D3 on anti-SRBC response was mediated by the inhibition of T cells.


Biomaterial and Therapeutic Approaches for the Manipulation of Macrophage Phenotype in Peripheral and Central Nerve Repair.
Injury to the peripheral or central nervous systems often results in extensive loss of motor and sensory function that can greatly diminish quality of life. In both cases, macrophage infiltration into the injury site plays an integral role in the host tissue inflammatory response. In particular, the temporally related transition of macrophage phenotype between the M1/M2 inflammatory/repair states is critical for successful tissue repair. In recent years, biomaterial implants have emerged as a novel approach to bridge lesion sites and provide a growth-inductive environment for regenerating axons. This has more recently seen these two areas of research increasingly intersecting in the creation of 'immune-modulatory' biomaterials. These synthetic or naturally derived materials are fabricated to drive macrophages towards a pro-repair phenotype. This review considers the macrophage-mediated inflammatory events that occur following nervous tissue injury and outlines the latest developments in biomaterial-based strategies to influence macrophage phenotype and enhance repair.


"How can I hug someone now [over the phone]?": Impacts of COVID-19 on peer recovery specialists and clients in substance use treatment.
The COVID-19 pandemic has disproportionately affected underserved, low-income, ethnoracial minority communities, as well as those with substance use disorders (SUDs). The workforce of peer recovery specialists (PRSs), individuals with lived substance use and recovery experience, has rapidly expanded in response to a shortage of access to substance use treatment, particularly for those from underserved communities. As PRSs are likely serving individuals disproportionately affected by the pandemic, it is important to understand how COVID-19 has affected the PRS role and the individuals with SUD who they are supporting. This study aimed to examine: (1) the impact of COVID-19 on the PRS role and experience, (2) the impact of COVID-19 on clients in or seeking SUD treatment, (3) facilitators for clients engaging in treatment and adapting to new changes, and (4) sustainability of new treatment methods post-pandemic. Findings suggest that PRSs have had to adapt their role and responsibilities to meet changing client needs; however, PRS strengths, such as their shared experience and expertise navigating treatment barriers, make them uniquely suited to assist clients during the pandemic. The study identified various barriers and facilitators to clients seeking treatment or living with SUD, such as the loss of interpersonal connection. PRSs also identified some drawbacks to utilizing telehealth, but identified this as a potentially sustainable approach to delivering care after the pandemic. Future research could explore how challenges to fulfilling the PRS role, as well as adaptations to overcome these challenges, have changed over time.


Distinguishing between stochasticity and determinism: Examples from cell cycle duration variability.
We describe a recent approach for distinguishing between stochastic and deterministic sources of variability, focusing on the mammalian cell cycle. Variability between cells is often attributed to stochastic noise, although it may be generated by deterministic components. Interestingly, lineage information can be used to distinguish between variability and determinism. Analysis of correlations within a lineage of the mammalian cell cycle duration revealed its deterministic nature. Here, we discuss the sources of such variability and the possibility that the underlying deterministic process is due to the circadian clock. Finally, we discuss the "kicked cell cycle" model and its implication on the study of the cell cycle in healthy and cancerous tissues.


Disposition of octachlorodibenzo-p-dioxin (OCDD) in male rats.
Octachlorodibenzo-p-dioxin (OCDD) is a widespread environmental contaminant which has been reported to be nontoxic after acute administration. The disposition of [14C]OCDD was studied in male Fischer 344 rats in order to better assess the significance of chronic environmental exposure to OCDD. Rats were treated with 50 micrograms OCDD/kg iv, and 50, 500, or 5000 micrograms/kg po and held in individual metabolism cages for 3 days. Additional rats treated iv were held up to 56 days to follow elimination of OCDD-derived radioactivity and to determine terminal tissue distribution. Feces was the major route of elimination after both routes of exposure with little radioactivity ever appearing in the urine. Gastrointestinal absorption was nonlinear between 500 and 5000 micrograms/kg, never exceeding 10% of the administered dose. Liver was the major depot, followed by adipose tissue and skin. No metabolites of OCDD were detected in tissues, bile, or excreta. The whole-body half-life for the elimination of OCDD was between 3 and 5 months. Repeated oral exposure resulted in linear accumulation of OCDD in the tissues. Thus, OCDD, while poorly absorbed, can accumulate upon low-dose, repeated exposure and concentrate in the liver and adipose tissue.


Nutritional status and growth centiles using anthropometric measures of school-aged children and adolescents from Multan district.
Nutritional status among children and adolescents is assessed using growth rates. The aim of this study was to assess age- and gender-specific height, weight, and body mass index (BMI) centiles among children and adolescents relative to World Health Organization (WHO) references. A sample of 1040 school-aged children and adolescents aged 3-18 years from Multan District in Pakistan were selected for the study between January and March 2020. Multistage stratified random sampling was used for sample selection. Centile curves of height, weight, and BMI for age and gender were obtained using the lambda-mu-sigma (LMS) method, and results were compared with WHO 2007 references. For boys and girls, the average height was 137.37 ± 8.24 and 135.62 ± 9.64 cm, average weight was 36.32 ± 6.84 and 35.21 ± 7.27 kg, and average BMI was 18.44 ± 2.67 and 18.36 ± 2.91, respectively. The height centiles of boys were higher than the WHO reference, and during the prepubertal period (age 8 years or older) the centiles were lower than the WHO reference. The height centiles of girls were higher than the WHO reference, and during the pubertal period (age 10 years or older) the centiles were lower than the WHO reference. The gender-wise BMI centiles were higher compared to the WHO reference. The prevalence of thinness, overweight, and obesity in boys and girls was significantly higher than the WHO reference. The results of this study on centiles are up-to-date and will be used as a standard for comparison.


Behavioural stimulation and sensation-seeking among prisoners: applications to substance dependency.
Sensation-seeking among prisoners with substance dependence difficulties (drug and/or alcohol) was examined. This topic is under-researched in a prisoner sample. The aims are to examine the association between sensation-seeking, other personality variables, and substance dependency among prisoners, and to examine if sensation-seeking can be refined. Adult male prisoners (n=200) completed self-report measures examining the constructs of interest. Sensation-seeking comprised extraversion and openness to experience. It was more appropriately described as Behavioural-Stimulation-and-Sensation-Seeking (BStim-SS). BStim-SS is related to drug and poly-substance dependency but not alcohol-only dependency. Increased impulsivity was related to all substance use dependencies. BStim-SS presents as a valuable concept to apply to forensic populations. It captures the need for behavioural and emotional stimulation and lends support to Reward Discounting theory as valuable concept to apply across substance dependency. Implications for practise include: • A need to identify a broader concept of sensation-seeking for prisoner samples; • The recognition of differences within substance dependent samples, with impulsivity presenting differently across drug and/or alcohol dependent groups; • Recognition that concepts regularly applied to community samples need to be examined more specifically among forensic samples to ascertain validity.


Thyroid function in premature infants. The hypothyroxinemia of prematurity.
Advances of perinatal and neonatal medicine have been associated with a progressive reduction in mortality of premature infants and a progressive increase in number of the surviving very low birth weight (VLBW) cohort less than 28 to 32 weeks gestation age. Hypothalamic-pituitary-thyroid (HPT) function is immature in most premature infants, and this is particularly true of the VLBW group. Accumulated information has allowed development of a unique nosology of HPT system disorders in these infants to facilitate thyroid function testing, test interpretation, and patient management.


Interventional stroke therapy: current state of the art and needs assessment.
The primary therapeutic strategy for ischemic stroke, as for MI patients, is early reperfusion. Improvement in stroke treatment will require dedicated stroke centers to emulate MI quality indicators such as minimizing the "door-to-balloon time". A critical element in achieving this goal will be organizing the existing multidisciplinary pool of carotid interventionalists to provide the endovascular component of the acute care for ischemic stroke patients.


Fintech and investment risk of digital finance: mediating role of clean energy and green bonds through the dynamics of spill over.
This study examines how financial technology (FinTech) and green bonds have affected the ability of firms to finance energy efficiency measures by using data obtained from a subset of Chinese companies listed on the A-share market between 2011 and 2021. We apply the quantile-on-quantile method, which allows us to examine the interdependence of time series in each economy separately and yields data on the global and national levels indicating the relationship between the variables. The results show that an increase in both direct and indirect financing for businesses, as well as inter-bank competition, can greatly mitigate the financial limitations that firms suffer as a result of FinTech expansion. Our estimates show that the energy efficiency of the countries we chose improves when they are financed with green bonds across all quantiles of the data. Organizations not owned by the state, SMBs, and the more rapidly developing eastern half of China promise to benefit the most from the moderating effect of FinTech because of the faster pace of development there. The immediate ameliorating effect that financial technology has on reduced lending criteria mostly benefits businesses with either a strong innovation rate or a poor social responsibility performance rate. This is because businesses sharing either of these features are more likely to experiment and develop new products. Both theoretical and practical repercussions of this finding are explored.


DNA unwinding activity of replication protein A.
Replication protein A (RP-A) is a heterotrimeric complex conserved in eukaryotic cells. It binds to single-stranded DNA and is essential for initiation and elongation of DNA replication. In this communication we give evidence that this protein can unwind DNA independent of magnesium and ATP, two essential cofactors for bona fide DNA helicase activity. RP-A can unwind up to at least 350 basepairs and appears to be required in stoichiometric amounts. The reaction is extremely sensitive to NaCl and MgCl2. This activity of RF-A is suggestive for a possible unwinding function in initiation of DNA replication in eukaryotes.


Effects of different boiling processes on chemical compositions of Lilii Bulbus soup.
Lilii Bulbus, an edible Chinese herbal medicine, has a long history in medicine. However, research on effectively boiling Lilii Bulbus is rare. To make the more nutritious Lilii Bulbus soup, the optimized boiling process, using an alternate heating mode by decoction pot carrying a mixture of water and Chinese liquor at the ration of 9:1, was established in this study. Compared to the soup prepared by the daily process, the polysaccharide amount improved by 54%, and the total heavy metals decreased by 33.5% using the optimized boiling process. In addition, the total saponins at 34.3 μg/g were determined in the soup prepared by the optimized process. Meanwhile, the colchicine content in the boiled Lilii Bulbus soup was undetectable using the optimized process. This research performs an optimized boiling process for making Lilii Bulbus soup, and provides a reference for generating high commercial value from Lilii Bulbus soup in the future.


Diabetic Choroidopathy: Choroidal Vascular Density and Volume in Diabetic Retinopathy With Swept-Source Optical Coherence Tomography.
To compare choroidal vascular density (CVD) and volume (CVV) in diabetic eyes and controls, using en face swept-source optical coherence tomography (SS-OCT). Prospective cross-sectional study. Setting: Multicenter. Total of 143 diabetic eyes-27 with no diabetic retinopathy (DR), 47 with nonproliferative DR (NPDR), 51 with NPDR and diabetic macular edema (DME), and 18 with proliferative DR (PDR)-and 64 age-matched nondiabetic control eyes. Complete ophthalmologic examination and SS-OCT imaging. En face SS-OCT images of the choroidal vasculature were binarized. CVD, calculated as the percent area occupied by choroidal vessels in the central macular region (6-mm-diameter circle centered on the fovea), and throughout the posterior pole (12 × 9 mm). The central macular CVV was calculated by multiplying the average CVD by macular area and choroidal thickness (obtained with SS-OCT automated software). Multilevel mixed linear models were performed for analyses. Compared to controls (0.31 ± 0.07), central macular CVD was significantly decreased by 9% in eyes with NPDR + DME (0.28 ± 0.06; ß = -0.03, P = .02) and by 15% in PDR (0.26 ± 0.05; ß = -0.04, P = .01). The central macular CVV was significantly decreased by 19% in eyes with PDR (0.020 ± 0.005 mm3, ß = -0.01, P = .01) compared to controls (0.025 ± 0.01 mm3). Choroidal vascular density and volume are significantly reduced in more advanced stages of diabetic retinopathy. New imaging modalities should allow further exploration of the contributions of choroidal vessel disease to diabetic eye disease pathogenesis, prognosis, and treatment response.


Geometric principles underlying the proliferation of a model cell system.
Many bacteria can form wall-deficient variants, or L-forms, that divide by a simple mechanism that does not require the FtsZ-based cell division machinery. Here, we use microfluidic systems to probe the growth, chromosome cycle and division mechanism of Bacillus subtilis L-forms. We find that forcing cells into a narrow linear configuration greatly improves the efficiency of cell growth and chromosome segregation. This reinforces the view that L-form division is driven by an excess accumulation of surface area over volume. Cell geometry also plays a dominant role in controlling the relative positions and movement of segregating chromosomes. Furthermore, the presence of the nucleoid appears to influence division both via a cell volume effect and by nucleoid occlusion, even in the absence of FtsZ. Our results emphasise the importance of geometric effects for a range of crucial cell functions, and are of relevance for efforts to develop artificial or minimal cell systems.


Antithrombotic papain-hydrolyzed peptides isolated from pork meat.
Atherothrombotic disease such as coronary artery disease and stroke is one of major causes of death. Platelets play important role in these arterial diseases. Suppression of platelet activity by materials may decrease incidence of the disease. The present study aimed to examine the peptides from pork meat with antithrombotic activity. Peptide fraction or hydrolyzate of defatted pork meat by papain was used as the starting material. Antithrombotic activity of the fraction was assessed by a share-induced platelet function test in vitro (haemostatometry) using non-anticoagulated rat blood, followed by a helium-neon laser-induced mouse carotid artery thrombosis test in vivo. The starting peptide fraction with mean molecular weight 2500 showed antithrombotic activity in vivo after oral administration to mice at 210 mg/kg body weight. The fraction with mean molecular weight 2517 further purified by cation exchange chromatography showed antithrombotic activity after oral administration at 70 mg/kg body weight. Antithrombotic activity of the purified peptide fraction was equivalent to that of aspirin at 50 mg/kg body weight. It is possible this pork peptide could be beneficial to prevent atherothrombosis.


Smartphone applications with sensors used in a tertiary hospital-current status and future challenges.
Smartphones have been widely used recently to monitor heart rate and activity, since they have the necessary processing power, non-invasive and cost-effective sensors, and wireless communication capabilities. Consequently, healthcare applications (apps) using smartphone-based sensors have been highlighted for non-invasive physiological monitoring. In addition, several healthcare apps have received FDA clearance. However, in spite of their potential, healthcare apps with smartphone-based sensors are mostly used outside of hospitals and have not been widely adopted for patient care in hospitals until recently. In this paper, we describe the experience of using smartphone apps with sensors in a large medical center in Korea. Among >20 apps developed in our medical center, four were extensively analyzed ("My Cancer Diary", "Point-of-Care HIV Check", "Blood Culture" and "mAMIS"), since they use smartphone-based sensors such as the camera and barcode reader to enter data into the electronic health record system. By analyzing the usage patterns of these apps for data entry with sensors, the current limitations of smartphone-based sensors in a clinical setting, hurdles against adoption in the medical center, benefits of smartphone-based sensors and potential future research directions could be evaluated.


Inferior calcar buttress reduction pattern for displaced femoral neck fractures in young adults: a preliminary report and an effective alternative.
Fracture reduction quality is of paramount importance for osteosynthesis. The aim of this study was to report the outcome of an inferior cortical buttress non-anatomic reduction pattern and internal fixation for displaced femoral neck fractures (Garden types III and IV) in young adults. A retrospective analysis of 46 displaced femoral neck fractures was performed, which were treated by closed reduction and internal fixation with parallel cannulated screws. There were 20 males and 26 females, with an average age of 50.3 years (19-60). According to the inferior cortical reduction quality seen in recorded intraoperative fluoroscopy, the patients were divided into two groups. Group I (n = 30) was anatomic cortical apposition as the two inferior cortices were smoothly contacted, and group II (n = 16) was buttress cortical apposition as the two inferior cortices were located in positive support contact (Gotfried reduction pattern). With a mean follow-up of 22.0 months, femoral neck length, neck-shaft angle, and clinical outcomes were compared. Thirty-nine patients (84.8%) achieved uneventful fracture union. Complications occurred in seven patients, six in group I (20%) and one in group II (6.3%), including displacement to varus, neck shortening, early fixation failure, nonunion, and avascular necrosis of the femoral head. No significant difference existed in the complication rate between the two groups (p = 0.216). Four patients (13.3%) in group I were converted to prosthetic replacement, but none in group II. For closed reduction and fixation of displaced femoral neck fractures in young adults, an inferior cortical buttress reduction pattern, though non-anatomic, can produce sustainable fracture stability and predictable clinical outcomes.


Vector-control personnel's knowledge, perceptions and practices towards insecticides used for indoor residual spraying in Limpopo Province, South Africa.
Contradictory arguments regarding the benefits and harm of insecticides, especially DDT, have caused concerns in different societal circles, threatening to undermine the achievements of the indoor residual spraying (IRS) programme in South Africa. These concerns were exacerbated by the screening of a documentary on South African Broadcasting Corporation (SABC) Television with anti-DDT sentiments. Consequently, Limpopo Malaria Control Programme (LMCP) Management advocated for an investigation to determine the potential effect of such campaigns on vector-control personnel's knowledge and perceived effects of insecticides on human health, with a view to improving the educational materials designed for use in training vector-control personnel. The study was a cross-sectional descriptive survey using a structured field-piloted questionnaire, administered to 233 randomly selected vector-control personnel. Ethical clearance was granted by the University of KwaZulu-Natal. Approval for the study was granted by the Department of Health, Limpopo. Participation in the study was voluntary and all respondents signed informed consent. Descriptive statistics were used to analyse the collected data. Most respondents (96.6%) had a positive perception of IRS as a method to control malaria. Despite their positive perception, 93.6% viewed IRS insecticides to be potentially harmful to the users. DDT was perceived to cause long-term reproductive and respiratory effects, whereas alpha-cypermethrin and deltamethrin were largely associated with skin irritation/itchiness and skin burn. Study participants were more worried about DDT's potential effects on their reproductive system, including poor sexual performance, decline in libido, miscarriage and bearing children with genetic defects. However, none reported personal experience of bearing a child with genetic defects or miscarriage.Most anti-insecticide messages, especially relating to DDT, emanated from sources external to the LMCP, mainly through radio (62%) and television (33.9%) and about 70% believed such messages. While most respondents preferred to work with a moderately itchy deltamethrin, DDT was admittedly the most effective insecticide. Vector-control personnel faced health and ethical dilemmas, in that, while they perceived insecticides used for IRS in Limpopo to be potentially harmful to the health of users, as purported through media, they also viewed IRS using insecticides to be effective in controlling malaria.


Using the H2O Automatic Machine Learning Algorithms to Identify Predictors of Web-Based Medical Record Nonuse Among Patients in a Data-Rich Environment: Mixed Methods Study.
With the advent of electronic storage of medical records and the internet, patients can access web-based medical records. This has facilitated doctor-patient communication and built trust between them. However, many patients avoid using web-based medical records despite their greater availability and readability. On the basis of demographic and individual behavioral characteristics, this study explores the predictors of web-based medical record nonuse among patients. Data were collected from the National Cancer Institute 2019 to 2020 Health Information National Trends Survey. First, based on the data-rich environment, the chi-square test (categorical variables) and 2-tailed t tests (continuous variables) were performed on the response variables and the variables in the questionnaire. According to the test results, the variables were initially screened, and those that passed the test were selected for subsequent analysis. Second, participants were excluded from the study if any of the initially screened variables were missing. Third, the data obtained were modeled using 5 machine learning algorithms, namely, logistic regression, automatic generalized linear model, automatic random forest, automatic deep neural network, and automatic gradient boosting machine, to identify and investigate factors affecting web-based medical record nonuse. The aforementioned automatic machine learning algorithms were based on the R interface (R Foundation for Statistical Computing) of the H2O (H2O.ai) scalable machine learning platform. Finally, 5-fold cross-validation was adopted for 80% of the data set, which was used as the training data to determine hyperparameters of 5 algorithms, and 20% of the data set was used as the test data for model comparison. Among the 9072 respondents, 5409 (59.62%) had no experience using web-based medical records. Using the 5 algorithms, 29 variables were identified as crucial predictors of nonuse of web-based medical records. These 29 variables comprised 6 (21%) sociodemographic variables (age, BMI, race, marital status, education, and income) and 23 (79%) variables related to individual lifestyles and behavioral habits (such as electronic and internet use, individuals' health status and their level of health concern, etc). H2O's automatic machine learning methods have a high model accuracy. On the basis of the performance of the validation data set, the optimal model was the automatic random forest with the highest area under the curve in the validation set (88.52%) and the test set (82.87%). When monitoring web-based medical record use trends, research should focus on social factors such as age, education, BMI, and marital status, as well as personal lifestyle and behavioral habits, including smoking, use of electronic devices and the internet, patients' personal health status, and their level of health concern. The use of electronic medical records can be targeted to specific patient groups, allowing more people to benefit from their usefulness.


Bone repair in mandibular body osteotomy after using 2.0 miniplate system--histological and histometric analysis in dogs.
The objective of this study was to evaluate the bone repair along a mandibular body osteotomy after using a 2.0 miniplate system. Nine adult mongrel dogs were subjected to unilateral continuous defect through an osteotomy between the mandibular 3rd and 4th premolars. Two four-hole miniplates were placed in accordance with the Arbeitgeimeinschaft für Osteosynthesefragen Manual. Miniplates adapted to the alveolar processes were fixed monocortically with 6.0-mm-length titanium alloy self-tapping screws, whereas miniplates placed near the mandible bases were fixed bicortically. At 2, 6 and 12 weeks, three dogs were sacrificed per period, and the osteotomy sites were removed, divided into three thirds (Tension Third, TT; Intermediary Third, IT; Compression Third, CT) and prepared for conventional and polarized light microscopy. At 6 weeks, while the CT repaired faster and showed bone union by woven bone formation, the TT and IT exhibited a ligament-like fibrous connective tissue inserted in, and connecting, newly formed woven bone overlying the parent lamellar bone edges. At 12 weeks, bone repair took place at all thirds. Histometrically, proportions of newly formed bone did not alter at TT, IT and CT, whereas significantly enhanced bone formation was observed for the 12-week group, irrespective of the third. The results demonstrated that although the method used to stabilize the mandibular osteotomy allowed bone repair to occur, differences in the dynamics of bone healing may take place along the osteotomy site, depending on the action of tension and compression forces generated by masticatory muscles.


The rapid extraction of paraquat from plasma using an ion-pairing technique.
A method for the quantitative extraction of paraquat from plasma is described. The method relies on the use of an organic-soluble ion pair of paraquat with dodecyl sulphate. The use of the extraction procedure in conjunction with the dithionite colour reaction gives a method which is suitable for emergency estimations with a sensitivity limit of 50 micrograms/l. The extraction procedure alone offers a new first step in the clean up of paraquat for analysis by other methods.


Trigeminal neuralgia: the role of magnetic resonance imaging.
We present a case of an epidermoid cyst in contact with the inferior and lateral aspects of the left trigeminal nerve, which resulted in secondary trigeminal neuralgia of the left mandibular branch of the trigeminal nerve. The symptoms were typical of trigeminal neuralgia, with no other neurological signs and symptoms. If patients present with trigeminal neuralgia, consideration should be given to routine visualisation of the entire course of the trigeminal nerve by magnetic resonance imaging (MRI) to identify cases of secondary trigeminal neuralgia.


The physiological role of DC-SIGN: a tale of mice and men.
The innate immune receptor DC-SIGN (dendritic cell-specific intercellular adhesion molecule-3 grabbing non-integrin) was discovered over a decade ago and was initially identified as a pattern recognition receptor. In addition to its ability to recognize a broad range of pathogen-derived ligands and self-glycoproteins, DC-SIGN also mediates intercellular adhesion, as well as antigen uptake and signaling, which is a functional hallmark of dendritic cells (DCs). Most research on DC-SIGN has relied on in vitro studies. The in vivo function of DC-SIGN is difficult to address, in part because there are eight genetic homologs in mice with no clear DC-SIGN ortholog. Here, we summarize the functions attributed to DC-SIGN based on in vitro data and discuss the limitations of available mouse models to uncover the physiological role of this receptor in vivo.


Synergistic antibacterial effect of multifunctional TiO2-X-based nanoplatform loading arginine and polydopamine for promoting infected wounds healing.
The gas therapy of some endogenous signaling molecules to treat diseases has caused extensive research, among which NO gas has shown great potential in fighting infection with various pathogens, promoting wound healing, etc. Here, we propose a photothermal/photodynamic/NO synergistic antibacterial nanoplatform by loading L-arginine (LA) on mesoporous TiO2 and then encapsulating it with polydopamine. The obtained TiO2-x-LA@PDA nanocomposite possesses both the excellent photothermal effect and ROS generation ability of mesoporous TiO2, and the release of nitric oxide (NO) from L-arginine under near-infrared (NIR) light irradiation, while the sealing layer of PDA could induce NIR-triggered NO controlled release. In vitro antibacterial experiments confirmed that the synergistic effect of TiO2-x-LA@PDA nanocomposites has excellent antibacterial effects against Gram-negative and Gram-positive bacteria, while in vivo experiments showed that it has lower toxicity. It is worth noting that compared with the pure photothermal effect and ROS, the generated NO showed a better bactericidal effect, and NO had a better ability to promote wound healing. In conclusion, the developed TiO2-x-LA@PDA nanoplatform can be used as a nanoantibacterial agent, which can be further explored in the related biomedical field of photothermal activation of multimodal combined antibacterial therapy.


Laparoscopic Roux-En-Y Gastric Bypass Improves Lipid Profile and Decreases Cardiovascular Risk: a 5-Year Longitudinal Cohort Study of 1048 Patients.
Dyslipidemia is a known risk factor for cardiovascular (CV) events. The aim of the study was to assess lipid profiles and their impact on CV risk changes in a large patient cohort 5 years after Roux-en-Y gastric bypass (RYGB). All patients who underwent primary RYGB for severe obesity in our two hospitals between January 1999 and December 2009 were included. The Framingham risk score was used. One thousand and forty-eight patients were included, 791 women and 257 men. Five-year complete lipid profile was available for 77% of patients. At 5 years, mean body mass index (BMI) decreased from 45.7 ± 6 to 31 ± 5.8 kg/m2 (p < 0.001), excess BMI loss (EBMIL) was 72.35 ± 22%, and total body weight loss (TWL) 31.5 ± 9%. Lipid values improved significantly. Total- and LDL-cholesterol levels dropped at 1 year from 5.4 to 4.48 mmol/L and 3.2 to 2.41 mmol/L, respectively, and slightly increased thereafter. Triglyceride levels dropped from 2 to 1.17 mmol/L at 1 year and remained unchanged. HDL levels rose continuously from 1.27 to 1.77 mmol/L at 5 years. Lipid profile improved more in patients with greater weight loss (%EBMIL ≥ 50 or %TWL ≥ 25%). Assuming that all patients were non-smokers and other baseline risk factors (hypertension, diabetes) remained unchanged at 5 years, the amelioration of the lipid profile itself yielded to a 27% reduction of CV risk (p < 0.001). RYGB results in sustained excess weight loss and in amelioration of the lipid profile from the first to fifth postoperative year. This improvement translates into significantly lower CV risk from the first year after surgery.


Bacterial diversity in Cr(VI) and Cr(III)-contaminated industrial wastewaters.
The bacterial community structure of a chromium water bath, a chromium drainage waste system, a chromium pretreatment tank, and a trivalent chromium precipitation tank from the Hellenic Aerospace Industry S.A. was assessed using 16S rRNA libraries and a high-density DNA microarray (PhyloChip). 16S rRNA libraries revealed a bacterial diversity consisting of 14 distinct operational taxonomic units belonging to five bacterial phyla: Alphaproteobacteria, Betaproteobacteria, Gammaproteobacteria, Actinobacteria, and Bacteroidetes. However, employing a novel microarray-based approach (PhyloChip), a high bacterial diversity consisting of 30 different phyla was revealed, with representatives of 181 different families. This made it possible to identify a core set of genera present in all wastewater treatment stages examined, consisting of members of Alphaproteobacteria, Betaproteobacteria, Gammaproteobacteria, Deltaproteobacteria, Epsilonproteobacteria, and Bacteroidetes. In the chromium pretreatment tank, where the concentration of Cr(VI) is high (2.3 mg/l), we identified the presence of Pseudomonadales, Actinomycetales, and Enterobacteriales in abundance. In the chromium precipitation tank, where the concentration of Cr(III) is high, the dominant bacteria consortia were replaced by members of Rhodocyclales and Chloroflexi. The bacterial community structure changed significantly with changes in the chromium concentration. This in-depth analysis should prove useful for the design and development of improved bioremediation strategies.


Comparing the effects of adapting to a weight on one leg during treadmill and overground walking: A pilot study.
Locomotor adaptation has been suggested as a way to improve gait symmetry in individuals post-stroke. Most perturbation methods utilize costly, specialized equipment. The use of a unilateral leg weight may provide a low cost, clinically translatable alternative. Furthermore, previous studies have suggested that adaptation context may affect movement outcomes. The purpose of this study was to assess the ability of a unilaterally applied ankle weight to drive locomotor adaptation and determine the effect of context (treadmill versus overground) in young, non-disabled participants. Eighteen young non-disabled adults were randomly assigned to receive 10min of walking on a treadmill with a weight (TG), overground with a weight (OG) or as a control on a treadmill/overground without a weight (CG). Outcomes measured before, during and after adaptation were: step length symmetry, single limb support symmetry and gait speed. After adding the weight, single limb support immediately became asymmetrical for all participants without changes in step length symmetry. After walking for 10min, TG step length became asymmetrical. After weight removal, both TG and OG had increased step length asymmetry. TG decreased single limb support asymmetry while OG did not. After walking overground without the weight, walking parameters eventually returned to baseline in both weighted groups. The control group showed no changes. A unilaterally applied ankle weight appears able to cause gait adaptation in young, non-disabled participants. However different adaptive changes in the gait pattern are made by the nervous system when the perturbation is applied in different contexts.


Catalysis of protein folding by an immobilized small-molecule dithiol.
The isomerization of non-native disulfide bonds often limits the rate of protein folding. Small-molecule dithiols can catalyze this process. Here, a symmetric trithiol, tris(2-mercaptoacetamidoethyl)amine, is designed on the basis of criteria known to be important for efficient catalysis of oxidative protein folding. The trithiol is synthesized and attached to two distinct solid supports via one of its three sulfhydryl groups. The resulting immobilized dithiol has an apparent disulfide E degrees ' = -208 mV, which is close to that of protein disulfide isomerase (E degrees ' = -180 mV). Incubation of the dithiol immobilized on a TentaGel resin with a protein containing non-native disulfide bonds produced only a 2-fold increase in native protein. This dithiol appeared to be inaccessible to protein. In contrast, incubation of the dithiol immobilized on styrene-glycidyl methacrylate microspheres with the non-native protein produced a 17-fold increase in native protein. This increase was 1.5-fold greater than that of a monothiol immobilized on the microspheres. Thus, the choice of both the solid support and thiol can affect catalysis of protein folding. The use of dithiol-decorated microspheres is an effective new strategy for preparative protein folding in vitro.


Can the choice of diet undermine the potential genetic risk of AT1R 1166A>C gene polymorphism?
Angiotensin II type 1 receptor (AT1R) gene 1166A>C polymorphism is strongly associated with the incidence of cardiovascular diseases and predicts the development of metabolic syndrome (MetS). There is little information about the gene-diet interactions associated with MetS. This investigation examined the interaction between dietary patterns and AT1R polymorphism in relation to development risk of MetS. A prospective, non-interventional, case-control study included 265 MetS patients and 262 healthy controls in an adult population from Croatia. Collected data included clinical variables, type of diet (Mediterranean, continental and mixed), biochemical tests and AT1R genotyping. AT1R 1166A>C genotyping was performed by PCR restriction fragment length polymorphism methods. To examine gene-diet interactions, a total predictive model was built using a hierarchical backward elimination approach. Participants on Continental-diet were nearly 20 times more likely to have MetS than those on Mediterranean or mixed diet (OR = 19.96; 95% CI 10.44-38.18). In multivariate prediction, control subjects with AT1R 1166AC or CC genotype had a higher risk for high triglycerides compared to the AA genotype carriers. 1166AC or CC genotype carriers more often chose Mediterranean or mixed-diet versus 1166AA genotype carriers whose choice often was continental diet. Our results are the first to suggest the possibility that the choice of diet can undermine the potential genetic risk of the AT1R polymorphism as polymorphism carriers may spontaneously choose the Mediterranean-diet.