Outcomes of hypoplastic left heart syndrome: analysis of National Inpatient Sample Database 1998-2004 versus 2005-2014.
Neonates with hypoplastic left heart syndrome (HLHS) were identified from the National Inpatient Sample dataset for the years 1998-2014. These patients were stratified into two chronological groups, past group (1998-2005) and recent group (2006-2014). A total of 20,649 neonates with HLHS were identified. Of them, 9179 (44.5%) were born in the past group and 11,470 (55.5%) in the recent group. Median birth weight was significantly less in the recent group (2967 g vs. 3110 g, p = 0.005). The patients in the recent group had more patients with low birth weight ( < 2.5 kg) and prematurity (8.7% vs 7.6% and 12.7% vs. 4.3%., respectively). In addition, recent group had more comorbidities including chromosomal anomalies, total anomalous pulmonary venous return, and kidney anomalies (5.6% vs. 3.6%, 2.3% vs. 1.7%, and 5.6% vs. 3.6%, respectively, p < 0.001); these were associated with a higher rate of extracorporeal membrane oxygenation utilization (9.2% vs. 4.5%, p < 0.001). Consequently, median length of stay was longer in the recent group (8 vs. 6 days, p < 0.001).Conclusion: Despite the higher frequency of comorbidities in recent group, the mortality rates decreased by 20% (from 25.3% to 20.6%, p < 0.001). Balloon atrial septostomy was performed less frequently in the recent group (23.3% vs. 16.1%, p < 0.001).What is known:• Hypoplastic left heart syndrome has the highest mortality among congenital cardiac defects during the first year of life.• Limited studies on patients' comorbidities and mortality rates trends over last two decades.What is new:• The study utilized a national database to compare in-hospital mortality and length of stay between the two time periods 1998-2005 and 2006-2014.• The recent group had more comorbidities (prematurity, chromosomal anomalies, total anomalous pulmonary venous return, and kidney anomalies), and there was higher rate of ECMO and longer length of stay, while mortality rates decreased by 20%.


The relation between liver vitamin content and the duration of Schistosoma mansoni infection in mice.
To study some changes that take place in the liver after schistosomal infection, the level of five vitamins of the B-complex group was estimated in non-infected mice and in 8, 16 and 20 weeks after the exposure of mice to cercariae of Schisostoma mansoni. Schistosomiasis caused a decrease in the level of thiamine, pantothenic acid, and niacin, but did not affect the concentration of riboflavin and pyridoxine in the liver.


[Returning to work after an acute coronary syndrome: When waiting is wasting].
Return to work (RTW) after acute coronary syndrome (ACS) is an important issue for the patient's future. The study aim was to determine whether RTW practice complies with guidelines or is delayed by failure in patient management. We analysed the factors influencing RTW beyond the 90-day period recommended by guidelines. We conducted a survey of 216 self-employed workers admitted to the hospital for ACS using self-report questionnaires and medical examination. Factors influencing RTW, occupational and cardiac features, and recall and source of medical information were investigated. Ninety-three of 216 patients did not return to work by 90 days, despite good cardiac performance in 30 cases (32 %). The mean sick leave duration was 93.3±103.7 days. Advice concerning return to work was completely missing for 44 % of patients. Cardiac performance was independent of sick leave duration, but was correlated with the likelihood of RTW (P<0.001). Patients assimilated about 70 % of the medical information they were provided, but only 53 % of work-related information. Recall of work-related information was better among patients admitted to a rehabilitation facility (65 %) compared to those who did not receive rehabilitation (P<0.05). Cardiologists should assess the patient's cardiac performance within 2 months after ACS. Patient management should also include cardiac rehabilitation or therapeutic education toward improving information recall.


Alteration of shock titration thresholds in the cat following intrathecal substance P administration.
Substance P (SP) was injected intrathecally (10 or 100 micrograms) into cats previously implanted with nerve-stimulating electrodes and the effect on shock titration thresholds was evaluated. Elevated shock thresholds were observed in 5 of 8 cats following the 100 micrograms dose of SP. In addition, one cat exhibited a decreased threshold and two cats showed a triphasic (increase, decrease, increase) response. Overt behavioral effects of intrathecal SP were mild, but suggested that injection of the drug was aversive.


Effects of maternal depression on family food insecurity.
We use data from the Early Childhood Longitudinal Study-Birth Cohort to estimate the effects of maternal depression, a condition that is fairly common and can be severe, on food insecurity, a hardship that has increased substantially in the U.S. Using various model specifications, we find convincing evidence that severe maternal depression increases the likelihood that young children experience food insecurity by 23-79%, with estimates depending on model specification and measures of depression and food insecurity. For household food insecurity, the corresponding estimates are 11-69%. We also find that maternal depression increases reliance on several types of public programs, suggesting that the programs play a buffering role.


Tubuloglomerular feedback in animals with unilateral, partial ureteral occlusion.
Previous experiments have shown that the sensitivity of the tubuloglomerular feedback system (TGF) is reduced by volume expansion in normal rats. This reduction in sensitivity is probably mediated by changes in the renal interstitial pressure. The present study was designed to investigate the TGF control system during volume expansion in rats with chronic, partial ureteral occlusion--hydronephrosis. Hydronephrosis was induced on the left or right side according to the method described by Ulm and Miller, in weanling Sprague-Dawley rats three weeks old. Three to six weeks later the rats were prepared for whole kidney and micropuncture experiments. Sham-operated animals were used as controls. Net interstitial pressure (that is, interstitial hydrostatic pressure minus interstitial oncotic pressure) was higher in the hydronephrotic, volume expanded animals than in the volume expanded controls. From findings in earlier investigations this increase in interstitial pressure would have been expected to reduce TGF sensitivity but this sensitivity was increased in the hydronephrotic kidneys, as indicated by a reduction in the turning point, the tubular flow rate at which 50% of the maximal stop-flow pressure response was observed (14.4 nl/min, sham-operated control 33.4 nl/min). Strong activity of the TGF mechanism was also indicated by a large proximal-distal difference in the single-nephron glomerular filtration rate (11.9 nl/min versus 3.3 nl/min in sham-operated controls) in the hydronephrotic kidney during volume expansion. Thus, in hydronephrotic kidneys in the latter condition the TGF mechanism was highly sensitive and activated to reduce the glomerular filtration rate. This mechanism may protect the diseased kidney from high intrapelvic pressures which otherwise could damage the kidney during saline volume expansion.


The Possible Role of Neurobeachin in Extinction of Contextual Fear Memory.
Established fear memory becomes vulnerable to disruption after memory retrieval and extinction; this labile state is critical for inhibiting the return of fear memory. However, the labile state has a very narrow time window after retrieval, and underlying molecular mechanisms are not well known. To that end, we isolated the hippocampus immediately after fear memory retrieval and performed proteomics. We identified Neurobeachin (NBEA), an autism-related regulator of synaptic protein trafficking, to be upregulated after contextual fear memory retrieval. NBEA protein expression was rapid and transient after fear memory retrieval at the synapse. Nbea mRNA was enriched at the synapses, and the rapid induction of NBEA expression was blocked by inhibition of the mammalian target of rapamycin (mTOR)-dependent signaling pathway. Mice with cornu ammonis 1 (CA1)-specific Nbea shRNA knockdown showed normal fear acquisition and contextual fear memory but impaired extinction, suggesting an important role of Nbea in fear memory extinction processes. Consistently, Nbea heterozygotes showed normal fear acquisition and fear memory recall but showed impairment in extinction. Our data suggest that NBEA is necessary either for induction of memory lability or for the physiological process of memory extinction.


Basic fibroblast growth factor and its receptor messenger ribonucleic acids are expressed in human ovarian epithelial neoplasms.
Our purpose was to determine whether basic fibroblast growth factor is present in, and synthesized by, human ovarian epithelial neoplasms and to evaluate the expression of gene for the basic fibroblast growth factor receptor. The synthesis of basic fibroblast growth factor and its receptor was investigated in seven primary human ovarian epithelial neoplasms. Neoplastic tissues were homogenized and the cytoplasmic extracts purified by heparin-sepharose chromatography with a linear salt gradient of 0.6 to 3 mol/L sodium chloride in Tris-hydrochloric acid. The in situ synthesis of basic fibroblast growth factor and its receptor was demonstrated by polymerase chain reaction. Total ribonucleic acid was reverse transcribed and then amplified with two oligonucleotide primers specific for the bovine and human basic fibroblast growth factor gene and its human receptor gene. As assessed by both bioassay and radioimmunoassay a peak of basic fibroblast growth factor-like activity was present in all tumors in the chromatographic fractions eluted with 3 mol/L sodium chloride. The mitogenic effect on bovine adrenocortical endothelial cell proliferation varied from 35% to 153% above control cultures. Levels of basic fibroblast growth factor-like immunoreactivity were between 4 and 33 ng/ml. Qualitatively similar results were obtained after purifying the cytoplasmic extract of dispersed human ovarian tumor cells. The mitogenic effect was completely abolished by a specific neutralizing anti-basic fibroblast growth factor antibody. Single major deoxyribonucleic acid bands of the expected size (354 and 661 bp) were detected in all tumors studied. The identify of this material with the human basic fibroblast growth factor sequence was confirmed by restriction enzyme analysis. These data demonstrate that both basic fibroblast growth factor and its receptor are present in and synthesized by human ovarian tumor cells. Thus basic fibroblast growth factor might stimulate their abnormal proliferation through an autocrine mechanism.


Expression of DDSG1, a novel gene encoding a putative DNA-binding protein in the embryonic chicken nervous system.
In an attempt to clone genes expressed in the gizzard of the chicken embryo by differential display, we obtained a cDNA of a gene encoding a protein with a putative nuclear localization signal and a DNA-binding motif and designated it DDSG1 (differential display-screened gene expressed in the gizzard-1). Besides its expression in the gizzard, the gene is expressed in central and peripheral nervous systems such as brain, spinal cord and dorsal root ganglia in specific patterns.


Catecholaminergic innervation of muscles in the hindgut of crustaceans. An ultrastructural study.
The crustacean species Pacifastacus leniusculus and Gammarus pulex were investigated by electron microscopy in a search for possible neuromuscular junctions in the hindgut, which has a rich supply of catecholaminergic fibres. True neuromuscular synapses were found in both species between nerve terminals containing dense-core vesicles (80-110 nm in diam.) and muscle fibres. We suggest that the dense-core vesicle terminals contain a catecholamine, and this is supported by ultrahistochemical tests for monoamines. Two types of junctions are found: one in which the nerve terminal is embedded in the muscle cell (both species) and one in which protrusions from the muscle cell meet nerve terminals (Pacifastacus). Gammarus pulex, which has only circular muscles in the hindgut, has only catecholaminergic innervation, whereas Pacifastacus leniusculus has circular and longitudinal muscles both with at least two types of innervation.


Characterization of a fast transient outward current in neocortical neurons from epilepsy patients.
A-type currents powerfully modulate discharge behavior and have been described in a large number of different species and cell types. However, data on A-type currents in human brain tissue are scarce. Here we have examined the properties of a fast transient outward current in acutely dissociated human neocortical neurons from the temporal lobe of epilepsy patients by using the whole-cell voltage-clamp technique. The A-type current was isolated with a subtraction protocol. In addition, delayed potassium currents were reduced pharmacologically with 10 mM tetraethylammonium chloride. The current displayed an activation threshold of about -70 mV. The voltage-dependent activation was fitted with a Boltzmann function, with a half-maximal conductance at -14.8 +/- 1.8 mV (n = 5) and a slope factor of 17.0 +/- 0.5 mV (n = 5). The voltage of half-maximal steady-state inactivation was -98.9 +/- 8.3 mV (n = 5), with a slope factor of -6.6 +/- 1.9 mV (n = 5). Recovery from inactivation could be fitted monoexponentially with a time constant of 18.2 +/- 7.5 msec (n = 5). At a command potential of +30 mV, application of 5 mM 4-aminopyridine or 100 microM flecainide resulted in a reduction of A-type current amplitude by 35% or 22%, respectively. In addition, flecainide markedly accelerated inactivation. Current amplitude was reduced by 31% with application of 500 microM cadmium. All drug effects were reversible. In conclusion, neocortical neurons from epilepsy patients express an A-type current with properties similar to those described for animal tissues.


Leo stent-assisted coil embolization of a giant middle cerebral artery aneurysm.
We report a case of a 70-year-old man harboring a wide-necked thrombosed giant aneurysm of the left middle cerebral artery (MCA) on the M1 segment. The patient presented with generalized tonic-clonic seizures. A computerized tomography scan showed a calcified aneurysmal wall with perianeurysmal swelling. The aneurysm was successfully embolized using closed-cell nitinol stent-assisted coiling (Leo, BALT Co., Montmorency, France).


Increased susceptibility to oxidation of vitamin E in mitochondrial fractions compared with synaptosomal fractions from rat brains.
The in vitro oxidation of vitamin E (alpha tocopherol) in rat brain synaptosomes and mitochondria by 2,2'-azo-bis-(2'-amidinopropane) dihydrochloride (ABAPH), a free radical generator, was studied. Subcellular fractions (300 micrograms total protein) were suspended in different buffers at pH 7.4 and incubated at 37 degrees C. In the presence of 0.5 mM ABAPH the mitochondrial alpha tocopherol began to get oxidized after a lag time or induction time of 15 min compared with a lag time of 30 min for the synaptosomal fraction. Thus the reserve of reducing compounds that are responsible for delaying tocopherol oxidation is less in mitochondria than in synaptosomes. More tocopherolquinone was produced during incubations without ABAPH compared with incubations in the presence of ABAPH suggesting that the mechanism of oxidation of tocopherol differs under these two conditions. When mitochondria were incubated in buffer without oxidants the production of tocopherolquinone preceded that of thiobarbituric acid reactive substances, an indicator of peroxidation of fatty acids. Therefore, alpha tocopherol is active as an anti-oxidant in mitochondrial membranes and the production of alpha tocopherolquinone could be a monitor of mild membrane oxidation under in vitro conditions. The ease of oxidation of mitochondrial tocopherol suggests a general vulnerability of the mitochondrial membranes to oxidation. Adding vitamin E or its water soluble analogs during in vitro experiments may improve the stability and viability of mitochondria. Furthermore, antioxidant protection by vitamin E may be crucial for the maintenance of tissues, such as brain, whose function is critically dependent upon the availability of high energy phosphates.(ABSTRACT TRUNCATED AT 250 WORDS)


DSM-III generalized anxiety disorder: an empirical investigation of more stringent criteria.
The diagnoses of generalized anxiety disorder (GAD) according to DSM-III and according to revised criteria (requiring 6 months' duration and 6 symptoms) were determined by the use of the National Institute of Mental Health Diagnostic Interview Schedule in a probability sample of 357 women. The DSM-III GAD lifetime rate of 45% was reduced by a factor of five when the revised definition was applied. The reduction was due chiefly to the longer duration criterion. Requiring a higher number of symptoms did not raise the threshold for the diagnosis, since 74% of persons with a period of 1 month or more of generalized anxiety reported six symptoms. Although chronicity was associated with more pervasive symptomatology, the excess in symptoms appears to be due to the very high prevalence of major depression (73%) among the newly defined (i.e., chronic) GAD positives.


Glycemic control in people with type 1 diabetes using a hybrid closed loop system and followed by telemedicine during the COVID-19 pandemic in Italy.
This study aims at evaluating the metrics of glycemic control in people with type 1 diabetes using the hybrid closed loop (HCL) system during the COVID-19 lockdown. This is a retrospective study of thirty adults with type 1 diabetes using HCL and followed with telemedicine at an Italian University Hospital. Data on metrics of glucose control were collected at different times: two weeks before the lockdown (Time 0), first two weeks of lockdown (Time 1), last two weeks of lockdown (Time 2) and first two weeks after the lockdown (Time 3). The primary endpoint was the change in glucose management indicator (GMI) across the different time points. GMI did not worsen over time (Time 1 vs Time 3, 7% vs 6.9%, P < 0.05), whereas a reduction of mean glucose (P = 0.004) and indices of glucose variability was observed. Time in range (TIR) significantly increased (68.5% vs 73.5%, P = 0.012), and time above range (TAR) level 2 (251-400 mg/dL) significantly decreased (P = 0.002). The improvement of TIR and glucose variability was mainly observed in participants < 35 years. Adults with type 1 diabetes using HCL showed a significant improvement of most of the metrics of glucose control during the COVID-19 lockdown.


The role of nonverbal and verbal communication in a multimedia informed consent process.
Nonverbal and verbal communication elements enhance and reinforce the consent form in the informed consent process and need to be transferred appropriately to multimedia formats using interaction design when re-designing the process. Observational, question asking behavior, and content analyses were used to analyze nonverbal and verbal elements of an informed consent process. A variety of gestures, interruptions, and communication styles were observed. In converting a verbal conversation about a textual document to multimedia formats, all aspects of the original process including verbal and nonverbal variation should be one part of an interaction community-centered design approach.


Increased frequency of apolipoprotein epsilon 4 allele in type II diabetes with hypercholesterolemia.
The apolipoprotein E (apoE) phenotype and allele frequencies were examined in type II (non-insulin-dependent) diabetic patients with normolipidemia (n = 134) and hypercholesterolemia (type IIa hyperlipoproteinemia, n = 35; type IIb hyperlipoproteinemia, n = 42). The frequencies of apoE4-present phenotypes (apoE4/3, apoE4/4, and apoE4/2) were highest in the type IIa group (51.4%), followed by the type IIb group (38.1%) and the normolipidemic group (16.4%), respectively, whereas the frequency of the most common phenotype, apoE3/3, was lowest in the type IIa group (48.6%), followed by the type IIb group (61.9%) and the normolipidemic group (79.9%), respectively. There were significant differences in the apoE phenotype frequencies between the normolipidemic group and the type IIa and IIb groups. The frequency of the epsilon 4 allele was significantly higher in the type IIa (28.6%) and IIb (20.2%) groups than in the normolipidemic group (8.9%), whereas the frequency of the epsilon 3 allele was significantly lower in the type IIa (71.4%) and IIb (78.6%) groups than in the normolipidemic group (89.2%). The frequency of the epsilon 2 allele tended to be lower in diabetic patients with hypercholesterolemia. In addition, these frequencies were also examined in nondiabetic subjects (n = 59). The frequency of the epsilon 4 allele tended to be higher in hypercholesterolemic diabetic subjects (24.1%) than in hypercholesterolemic nondiabetic subjects (15.3%). These data suggest that diabetic patients with the epsilon 4 allele may be more susceptible to hypercholesterolemia than diabetic patients without the epsilon 4 allele and possibly nondiabetic subjects with the epsilon 4 allele, although the underlying mechanism is unknown.


Increased Matrix Metalloproteinase-1 Activation Enhances Disruption and Regression of k-RasV12-Expressing Arteriovenous Malformation-Like Vessels.
This study sought to identify potential mechanisms by which k-RasV12-expressing endothelial cell (EC) tubes demonstrate an increased propensity to regress compared with controls. Activated k-Ras mutations play a role in a variety of pathological conditions, including arteriovenous malformations, which are prone to bleed, causing serious hemorrhagic complications. ECs expressing active k-RasV12 demonstrate markedly excessive lumen formation with widened and shortened tubes accompanied by reduced pericyte recruitment and basement membrane deposition, leading to deficient capillary network assembly. The current study showed that active k-Ras-expressing ECs secreted greater amounts of MMP-1 proenzyme compared with control ECs, and readily converted it to increased active MMP-1 levels through the action of plasmin or plasma kallikrein (generated from their added zymogens). Active MMP-1 degraded three-dimensional collagen matrices, leading to more rapid and extensive regression of the active k-Ras-expressing EC tubes, in conjunction with matrix contraction, compared with control ECs. Under conditions where pericytes protect control EC tubes from plasminogen- and MMP-1-dependent tube regression, this failed to occur with k-RasV12 ECs, due to reduced pericyte interactions. In summary, k-RasV12-expressing EC vessels showed an increased propensity to regress in response to serine proteinases through accentuated levels of active MMP-1, a novel pathogenic mechanism that may underlie hemorrhagic events associated with arteriovenous malformation lesions.


Assessment of therapeutic benefit of antiviral therapy in chronic hepatitis C: is hepatic venous pressure gradient a better end point?
Chronic hepatitis C is a major healthcare problem. The response to antiviral therapy for patients with chronic hepatitis C has previously been defined biochemically and by PCR. However, changes in the hepatic venous pressure gradient (HVPG) may be considered as an adjunctive end point for the therapeutic evaluation of antiviral therapy in chronic hepatitis C. It is a validated technique which is safe, well tolerated, well established, and reproducible. Serial HVPG measurements may be the best way to evaluate response to therapy in chronic hepatitis C.


The pitfalls of treating all actinic keratoses as squamous cell carcinomas.
The greatest difficulties in managing a patient with numerous actinic keratoses is deciding the order in which to treat the specific lesions and what modality to use. The patient with a small number of lesions is probably most conveniently and cost effectively treated using destructive techniques like cryosurgery, electrodesiccation or photodynamic therapy with lasers. However, patients with large numbers of lesions are probably best managed using a topical chemotherapy agent, like 5-florouracil or imiquimod. If the patient's health insurance company limits coverage for the treatment of a specific number AK's per visit, it may be most prudent and logical to begin treatment of the largest or most rapidly growing AK's first and continue treatment of remaining lesions at subsequent visits until all lesions have been eradicated.


Transcriptionally less active prodynorphin promoter alleles are associated with temporal lobe epilepsy: a case-control study and meta-analysis.
We performed an association study in a population of patients with Mesial Temporal Lobe Epilepsy (TLE) with Hippocampal Sclerosis (MTEHS) together with a systematic revision of the literature to investigate the role of transcriptionally less active polymorphic alleles of Prodynorphin (PDYN) gene in this pathology. We included 102 patients with a diagnosis of MTEHS and 86 healthy controls. The positive antecedent of family history for epileptic events defined a TLE subgroup with familial predisposition for epileptic disorders. The PDYN promoter polymorphism was genotyped by means of a PCR assay. For meta-analysis, we identified case-control association studies between TLE and PDYN by searching PUBMED. The pooled OR was estimated using a fixed effects model under dominant and co-dominant heredity models. No differences in genotypic and allelic frequencies were found between cases and controls (p=0.61) in our population, neither in the whole cohort nor in the analysis limited to TLE with familial predisposition (p=0.71). The Meta-Analysis included 591 TLE patients and 1117 healthy controls. We found an association between L allele (p=0.003; OR=1.40; IC 95=1.12-1.74) and a modestly higher risk to develop TLE in the group of patients with familial predisposition. Therefore, functional allelic variants in the PDYN promoter might modify the risk to develop TLE in subjects with familial predisposition.


Free heme and the polymerization of sickle cell hemoglobin.
In search of novel control parameters for the polymerization of sickle cell hemoglobin (HbS), the primary pathogenic event of sickle cell anemia, we explore the role of free heme, which may be excessively released in sickle erythrocytes. We show that the concentration of free heme in HbS solutions typically used in the laboratory is 0.02-0.04 mole heme/mole HbS. We show that dialysis of small molecules out of HbS solutions arrests HbS polymerization. The addition of 100-260 μM of free heme to dialyzed HbS solutions leads to rates of nucleation and polymer fiber growth faster by two orders of magnitude than before dialysis. Toward an understanding of the mechanism of nucleation enhancement by heme, we show that free heme at a concentration of 66 μM increases by two orders of magnitude the volume of the metastable clusters of dense HbS liquid, the locations where HbS polymer nuclei form. These results suggest that spikes of the free heme concentration in the erythrocytes of sickle cell anemia patients may be a significant factor in the complexity of the clinical manifestations of sickle cell anemia. The prevention of free heme accumulation in the erythrocyte cytosol may be a novel avenue to sickle cell therapy.


Estimation of testosterone and androstenedione in the plasma and testes of cryptorchid offspring of mice treated with oestradiol during pregnancy.
The injection of pregnant mice with 5 mg oestradiol dipropionate induced a high proportion of bilateral cryptorchidism in the male offspring. The ectopic testes were reduced in size and occupied one of three different positions in the abdomen: pararenal, paravesicular or inguinal. The seminal vesicles were found to be similarly reduced in size whereas the adrenals and pituitaries appeared to be unaffected. The total content of testosterone was reduced in the pararenally placed gonads but was not significantly different from that of the controls when the testes were in the inguinal region. The content of androstenedione was not significantly altered. The concentration of both hormones, however, was increased in all cases. Plasma testosterone levels were lower in all the offspring of treated mothers, especially in those with high ectopia.


Fibula Nailing: A Retrospective Review of 110 Consecutive FibuLock Nails.
To evaluate the treatment of unstable lateral malleolar fractures using a fibula nail with both proximal and distal locking capabilities. Retrospective review of 110 single-surgeon consecutive fibula nails. Single-surgeon, private practice community hospital. One hundred ten fractures, 92 OTA/AO 44B and 18 OTA/AO 44C. FibuLock fibula nail (Arthrex, Naples, FL). Demographic, operative, clinical, and radiographic outcome data. One hundred two patients/102 fractures met criteria. Ninety percent had a f/u of ≥12 months (mean 12.2 months). All fractures healed. There were no superficial or deep infections, no nonunions, or malunions. Two fractures required conversion to plate fixation intraoperatively because of excessive comminution which precluded the use of a nail, while one patient sustained an iatrogenic superficial peroneal nerve neuroma. No patients reported implant irritation, and none have required implant removal. Fibula nails with proximal locking capabilities offer an alternative to plating with the potential for lower complication rates and lower need for implant removal. Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.


Influence of dietary emamectin benzoate on the biological responses of monosex (all-male) Oreochromis niloticus (L.) fries.
The application of antiparasitic drugs plays a crucial role in the removal of infectious parasites in aquaculture. Emamectin benzoate (EB) is predominantly used as a feed premix against ectoparasites on temperate fish. This study evaluated the influence of 14 days of EB-dosing at 0-10 times the recommended dose (1X: 50 μg/kg biomass/day) on the biological responses and accrual/depletion of EB-residues in a tropical fish monosex Oreochromis niloticus fries. A significant dose-dependent reduction in feed intake by 3.50% in 1X and 43.00% in 10X groups, and an increase in mortalities from 2.92% (1X) to 11.25% (10X) during the EB-dosing period was noted. A significant increase in glucose and alkaline phosphatase and reduction in calcium and chloride ions, superoxide dismutase (SOD) and acetylcholinesterase levels in the muscle and/or brain tissue was observed. On day 21 post-EB-dosing, the levels of muscle glucose and SOD reached normalcy in the 1X group, while the levels of other biomarkers failed to recuperate. The EB-residue levels peaked on day 14 EB-dosing (2.77 ng/g) in the 1X group and decreased later with detectable levels (0.03 ng/g) even on day 21 post-EB-dosing. The EB-residue levels were within the permissible limits of the Canadian Food Inspection Agency and the European Commission. The EB-dosing negatively influenced the health of O. niloticus by altering the physiological state in a dose- and time-dependent way. The results suggested that the use of EB might be plausibly risky in tropical aquaculture.


The association between placebo arm inclusion and adverse event rates in antidepressant randomized controlled trials: An examination of the Nocebo Effect.
Antidepressant efficacy is influenced by patient expectations and, in randomized controlled trials (RCTs), the probability of receiving a placebo. It is unclear whether tolerability demonstrates a similar pattern. This study aimed to determine whether study design influences adverse event (AE) rates in antidepressant trials for subjects receiving active treatment or placebo. RCTs comparing one antidepressant to another antidepressant, placebo, or both in major depressive disorder (MDD) (1996-2018) were retrieved from Medline and PsycINFO. Clinicaltrials.gov was searched for unpublished trials. Of 1,997 studies screened, 77 trials were included. Studies were classified as drug-drug, drug-drug-placebo, or drug-placebo based on design and overall number of subjects experiencing any AE was recorded. Subgroup meta-analysis of proportions and meta-regression techniques were used to compare AE rates across study designs in patients receiving active antidepressant treatment and placebo. Among the actively treated, AE rates were lower in drug-drug trials (58.5%) compared to drug-drug-placebo (75.7%) and drug-placebo (76.4%) (the model reported coefficients for percent differences between AE rates of different study designs were B=17.0, p<0.001 and B=17.8, p<0.001, respectively). AE rates in patients receiving placebo were not different between study designs. The present study is limited by the diverse range of study populations, variability in reporting of AEs, and specific antidepressants employed in the included trials. The inclusion of a placebo arm in the study design was unexpectedly associated with higher rates of AEs among patients receiving active medication in antidepressant trials. This observation has important implications for interpretation of trial tolerability findings.


Crassulacean acid metabolism in Kalanchoë species collected in various climatic zones of Madagascar: a survey by δ13C analysis.
The carbon isotope compositions of samples of Kalanchoë species collected at the natural stands in Madagascar were determined. The results suggest that all species of the genus Kalanchoë are capable of crassulacean acid metabolism. The observed δ13C values cover the whole range from -10 to -30‰. This high diversity of the δ13C values was found among the species of the genus as well as, in certain cases, within a single species. This suggest that the CAM patterns in Kalanchoë are generally very flexible. The δ13C values show a clear correlation with the climate of the habitats from where the samples derived. Values indicative of CO2 fixation taking place exclusively during the night were found in the dry regions of Madagascar, whereas δ13C values indicative of mixed CO2 fixation during night and day or of CO2 fixation entirely during the day are distributed in the humid zones.


A new way to evaluate the germinative compartment in human epidermis, using [3H]thymidine incorporation and immunoperoxidase staining of 67 K polypeptide.
We have used tritiated thymidine (3HT) labelling and immunoperoxidase staining of 67 K polypeptide in human epidermis to study normal skin before and after irritation induced by application of croton oil (20% and 50% in olive oil). By this double labelling method, it was possible to identify, on the same skin section, DNA-synthesizing nuclei and epidermal cells which contained 67 K polypeptide. Our results clearly indicate that the germinative compartment of normal epidermis is a mixed population comprising basal and adjacent suprabasal cells; as a rule, absence of expression of 67 K polypeptide, which characterizes all basal cells, could not be regarded as a good marker to distinguish the germinative from the differentiating compartments. In mild primary irritation, the ratio of 3HT-labelled undifferentiated cells to keratinizing ones was similar to that observed in normal epidermis. In severe irritation, this homeostatic process was altered, as 3HT-labelled cells were mainly 67 K negative.


Temperature dependence of phalloidin response in isolated rat hepatocytes.
Below 21 degrees C isolated hepatocytes are insensitive to phalloidin. Between 21 and 30 degrees C the amount of affected cells increases to nearly maximal values, whereas a further rise of the temperature has little additional effect. These findings suggest that phase transition of membranal lipids might be responsible for the unusual temperature characteristics. The fluidity of lipids seems to control an early step of the phalloidin response.


Paroxysmal nocturnal hemoglobinuria: Differential gene expression of EGR-1 and TAXREB107.
Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal defect of hematopoietic stem cells characterized by deficiency in GPI-anchored surface proteins. It is not yet known how GPI-deficient stem cells are able to expand within the bone marrow and contribute considerably to the hematopoiesis. In PNH, as well as in AA and MDS, genetic instability and increased mutation frequency have been detected. Therefore, a second event is very likely, such as additional mutations, leading to clonal expansion of GPI-deficient bone marrow stem cell in PNH. In order to elucidate the molecular basis of clonal expansion in PNH, we identified several genes differentially expressed in normal and GPI-deficient cells of PNH patients by combination of RNA fingerprinting and cDNA array hybridization. Expression of two of these genes, EGR-1 and TAXREB107, has been further investigated. EGR-1 is upregulated in granulocytes of all PNH patients analyzed so far. In contrast, significant upregulation of TAXREB107 is present only in some of our PNH patients. Further analysis confirmed their overexpression in PNH and excluded a possible secondary event character of observed overexpression. Moreover, similar levels of expression in cases of other clonal diseases, such as MPS and MDS, has been identified. Our data suggest that additional genetic alterations apart from PIG-A mutations could be present in PNH granulocytes. In addition, these genetic changes might contribute to clonal expansion of GPI-deficient cells in PNH.


Persistent hyperplastic primary vitreous. Surgical treatment.
Instruments designed for pars plana vitrectomy can be used to manage selected complicated congenital cataracts such as those with persistent hyperplastic primary vitreous (PHPV). We have applied closed-eye vitrectomy techniques through a limbal approach in seven eyes with PHPV. A clear pupillary space was achieved in all cases and two eyes achieved useful postoperative vision. The management of children with complicated congenital cataracts, such as with PHPV, is discussed.


Metabolic reprogramming of cancer-associated fibroblasts in pancreatic cancer contributes to the intratumor heterogeneity of PET-CT.
Intratumor heterogeneity of positron emission tomography-computed tomography (PET-CT) is reflected by variable 18F-fluorodeoxyglucose (FDG) uptake. Increasing evidence has shown that neoplastic and non-neoplastic components can affect the total 18F-FDG uptake in tumors. Cancer-associated fibroblasts (CAFs) is considered as the main non-neoplastic components in tumor microenvironment (TME) of pancreatic cancer. Our study aims to explore the impact of metabolic changes in CAFs on heterogeneity of PET-CT. A total of 126 patients with pancreatic cancer underwent PET-CT and endoscopic ultrasound elastography (EUS-EG) before treatment. High maximum standardized uptake value (SUVmax) from the PET-CT was positively correlated with the EUS-derived strain ratio (SR) and indicated poor prognosis of patients. In addition, single-cell RNA analysis showed that CAV1 affected glycolytic activity and correlated with glycolytic enzyme expression in fibroblasts in pancreatic cancer. We also observed the negative correlation between CAV1 and glycolytic enzyme expression in the tumor stroma by using immunohistochemistry (IHC) assay in the SUVmax-high and SUVmax-low groups of pancreatic cancer patients. Additionally, CAFs with high glycolytic activity contributed to pancreatic cancer cell migration, and blocking CAF glycolysis reversed this process, suggesting that glycolytic CAFs promote malignant biological behavior in pancreatic cancer. In summary, our research demonstrated that the metabolic reprogramming of CAFs affects total 18F-FDG uptake in tumors. Thus, an increase in glycolytic CAFs with decreased CAV1 expression promotes tumor progression, and high SUVmax may be a marker for therapy targeting the neoplastic stroma. Further studies should clarify the underlying mechanisms.


Purification of Ciliary Tubulin from Chlamydomonas reinhardtii.
Cilia and flagella play essential roles in environmental sensing, cell locomotion, and development. These organelles possess a central microtubule-based structure known as the axoneme, which serves as a scaffold and is crucial for the function of cilia. Despite their key roles, the biochemical and biophysical properties of the ciliary proteins are poorly understood. To address this issue, we have developed a novel method to purify functional tubulins from different parts of the axoneme, namely the central pair and B-tubule. We use the biflagellate green alga Chlamydomonas reinhardtii, a model organism for studying cilia due to the conserved structure of this organelle, availability of genetic tools and a large collection of mutant strains. Our method yields highly purified functional axonemal tubulins in sufficient quantities to be used for in vitro biochemical and biophysical studies, such as microtubule dynamic assays. It takes 7 to 8 days to grow enough cells; the isolation of the flagella and the purification of the axonemal tubulins require an additional two full days.© 2020 Wiley Periodicals LLC. Basic Protocol 1: Growth and harvest of large volume of cell culture Support Protocol: Assembly of homemade concentration apparatus Basic Protocol 2: Isolation of flagella Basic Protocol 3: Tubulin extraction and purification.


Inhibition of gamma-aminobutyric acid uptake into astrocytes by pentobarbital.
Pentobarbital (0.5-2mM), but not phenobarbital, was found to inhibit the uptake of gamma-aminobutyric acid into mouse astrocytes in primary cultures up to 45%. This inhibition was additive to a reduction in uptake rate caused by excess potassium. Its possible role in the pharmacological action of pentobarbital is discussed.


Visible-light-driven photocatalytic and chemical sensing properties of SnS2 nanoflakes.
This work demonstrated the successful and facile large-scale synthesis and characterizations of SnS2 nanoflakes. The detailed morphological studies revealed that the synthesized products were nanoflakes and were grown in large quantity. The XRD pattern and detailed compositional studies confirmed that the synthesized SnS2 nanoflakes were well-crystalline and possessing hexagonal SnS2 phase. The synthesized SnS2 nanoflakes were used as efficient photocatalysts for photocatalytic degradation and effective electron mediators for the fabrication of chemical sensor. The photocatalytic properties of SnS2 nanoflakes towards the photocatalytic degradation of Rhodamine B dye under visible light irradiation showed reasonably good degradation of ~61%. Moreover, the as-synthesized SnS2 nanoflakes were used as efficient electron mediators for the fabrication of nitroaniline chemical sensor by simple I-V technique. Very high-sensitivity of ~ 505.82±0.02 mAcm(-2).(mole/L)(-1) and experimental detection limit of ~15×10(-6) (mole/L) in a short response time of ~10.0 s with LDR in the range of 15.6×10(-6)-0.5×10(-3) mole L(-1) were observed for the fabricated nitroaniline chemical sensor. The observed results indicated that the SnS2 nanoflakes can efficiently be used as visible-light-driven photocatalysts and the fabrication of ultra-high sensitive chemical sensors.


An international simulated-use study to assess nurses' preferences between two lanreotide syringes for patients with neuroendocrine tumours or acromegaly (PRESTO 3).
PRESTO 3 evaluated nurses' preference for the Somatuline® Autogel® syringe versus the Lanreotide Pharmathen syringe after injection-pad testing. This international simulated-use study included oncology/endocrinology nurses with ≥ 1 years' experience in managing neuroendocrine tumours (NETs) and/or acromegaly. Each nurse tested both syringes twice in a randomised order before completing an electronic survey. The primary objective was to assess overall preference (%, 95% confidence interval [CI]) for the Somatuline Autogel syringe versus the Lanreotide Pharmathen syringe. Secondary objectives included rating syringe performance and ranking the importance of syringe attributes. Ninety-four nurses were enrolled: mean age, 41.0 (SD, 11.5) years. The percentage of nurses stating a preference ("strong" or "slight") for the Somatuline Autogel syringe (86.2% [95% CI 77.5-92.4%]) was significantly higher than 50% (p < 0.0001). Performance rating was significantly higher for the Somatuline Autogel syringe versus Lanreotide Pharmathen syringe for 10 of the 11 attributes tested (p < 0.05). The syringe attributes considered most important when injecting patients in routine clinical practice were "easy to use from preparation to injection" (30.9%) and "comfortable to handle during use from preparation to injection" (16.0%). The attribute most commonly rated as least important was "fast administration from preparation to injection" (26.6%). Nurses strongly preferred the user experience of the Somatuline Autogel syringe over the Lanreotide Pharmathen syringe. "Ease of use" and "comfortable to handle" were the most important syringe attributes, and performance rating was significantly higher with Somatuline Autogel versus Lanreotide Pharmathen syringe for all but one attribute.


Update on Pediatric Brain Tumors: the Molecular Era and Neuro-immunologic Beginnings.
To provide an update on the current landscape of pediatric brain tumors and the impact of novel molecular insights on classification, diagnostics, and therapeutics. Scientific understanding of the genetic basis of central nervous system tumors has expanded rapidly over the last several years. The shift in classification of tumors to a molecularly based schema, accompanied by a growing number of early phase clinical trials of therapies aimed at inhibiting tumoral genetic and epigenetic programs, as well as those attempting to harness and magnify the immune response, has allowed a deeper pathophysiologic understanding of brain tumors and simultaneously provided opportunities for novel treatment. Over the last 5 years, there has been tremendous growth in the field of pediatric neuro-oncology with increasing understanding of the genetic and epigenetic heterogeneity of CNS tumors. Attempts are underway to translate these insights into tumor-specific treatments.


The Behaviors of the Levator Veli Palatine Muscle Between 2 Surgical Conditions in Dog: The Comparison of Furlow and Pushback Methods.
This study was conducted to compare the velopharyngeal function among the beagle dogs which the levator veli palatini (LVP) muscles construction has been experimentally changed. Four groups of LVP muscle reconstruction were made (normal LVP, cut LVP, end-to-end sutured LVP, and overlapped-sutured LVP at the midline). Levator veli palatini contraction was induced by electrical stimulation or a hypercapnia condition to analyze the strength of the velopharyngeal closure using balloon with a blood pressure meter, and the electromyogram in those operated beagle dogs. Under a hypercapnia condition, the velopharyngeal function did not differ significantly among the 4 groups in the terms of velopharyngeal pressure. The strongest closure was shown at the overlapped sutured LVP group by electrical stimulation. The reconstruction of overlapped sutured LVP showed the most effective closure. This study suggested that the palatoplasty should be conducted along the overlapped LVP (like Furlow method).


Traumatic aortic arch false aneurysm after blunt chest trauma in a motocross rider.
This article details a case report of a traumatic aortic arch false aneurysm after blunt chest trauma. Thoracic aorta false aneurysms are a rare and life-threatening complication of aortic surgery, infection, genetic disorders and trauma.


Perioperative Brain Injury in Children with Aortic Arch Anomalies: A Retrospective Study of Risk Factors and Outcomes.
Complex pediatric cardiac disease is associated with brain impairment and neurodevelopmental disorders, particularly in patients requiring cardiac surgery for aortic arch anomalies. This study examines the incidence, risk factors, and outcomes of perioperative brain injury in children undergoing aortic arch repair who had aortic arch anomalies. A total of 145 children with aortic arch anomalies in our center undergoing aortic arch repair between January 2014 and December 2022 were enrolled. There were 129 (89.0%) with coarctation of the aorta (COA) and 16 (9.7%) with interrupted aortic arch (IAA). Risk factor analysis of brain injuries was done using perioperative imaging and included symptoms of hemorrhagic stroke, arterial ischemic stroke, white matter injury, cerebral sinus venous thrombosis, and other pathologies. Preoperatively, 50/145 (34.5%) patients had brain injuries. Multivariate analysis showed that an increased risk of hemorrhagic stroke was associated with newborns (odds ratio [OR], 2.09 [95% CI 0.08-3.50]), isolated COA (OR, 3.69 [95% CI 1.23-7.07]), mechanical ventilation (MV) ([OR, 2.56 [95% CI 1.25-4.03]), and sepsis (OR, 1.73 [95% CI 0.46-3.22]). Newborns ([OR, 1.91 [95% Cl 0.58-3.29]) and weight-for-age z score ([OR, -0.45 [95% CI -0.88 to -0.1]) were associated with an increased risk of white matter injury. New postoperative brain injuries were present in 12.9% of the patients (16/124). Deep hypothermic circulatory arrest (DHCA) was associated with new postoperative brain injuries compared with deep hypothermic low-flow (DHLF) plus antegrade cerebral perfusion (ACP) (([OR, 2.67 [95% CI, 0.58-5.75])). Isolated COA was almost associated with new postoperative brain injuries (OR, 1.13 [95% CI, -0.04 to 2.32]). Children diagnosed with isolated COA appeared to have a higher risk of perioperative brain injury, but the underlying mechanisms are still unclear. We focused on the intrinsic mechanism by which changes in hemodynamics caused by COA result in perioperative brain injury. Further research will be needed to optimize the personalized treatment and cerebral perfusion techniques for complex pediatric cardiac surgery.


A pore-scale investigation of microplastics migration and deposition during unsaturated flow in porous media.
Microplastics are ubiquitous in the natural environment and have the potential to endanger the natural environment, ecology and even human health. A series of microfluidic experiments by using soft lithography technology were carried out to investigate the effect of flow rate, particle volume fraction, particle size and pore/throat ratio on microplastics migration and deposition at the pore scale. We discovered a range of deposition patterns of the spherical microplastics from no particle deposition, to discontinuous particle layer, and to continuous particle layers in the retained liquid in the pores, depending on the particle size and volume fraction. Several metrics, including air saturation, probability of particle detainment, expansion ratio and thickness of residual liquid, were quantified to examine the role of various parameters on particle migration and retention of microplastics. At low flow rate (Q = 0.05 μL/min), microplastics migration and deposition were sensitive to changes in particle volume fraction, particle size and pore/throat ratio. In contrast, at high flow rates (Q > 5 μL/min), the migration and retention of particles were mainly controlled by strongly channelized air invasion pattern, while the particle volume fraction, particle size and pore/throat size ratio have only secondary influence. At intermediate range of flow rates, microplastics migration and deposition were dramatically impacted by flow rate, particle volume fraction, particle size and pore/throat ratio. This work improves the understanding of the mechanisms of particle migration and retention in porous media and can provide a reference for more accurate assessment of the exposure levels and times of microplastics in soil and groundwater systems.


Sequence of a conditionally essential region of bacteriophage T3, including the primary origin of DNA replication.
The 3526 base-pair nucleotide sequence from near the end of bacteriophage T3 gene 1 to within the coding sequence of gene 2.5 is given. It includes the complete coding sequences for nine known or presumptive proteins, most of which are only conditionally essential for phage growth. The sequence includes five promoters for the phage RNA polymerase, the terminator for early (host enzyme-catalyzed) transcription, and two recognition sites for RNAase III. The primary origin of T3 DNA replication that is utilized by the phage in vivo has been localized to a 142 base-pair region. It has several features in common with the phage T7 origin of DNA replication, and exhibits considerable homology to recognition sites for the mRNA processing enzyme RNAase III. It is proposed that the primary origin of T3 DNA replication may have evolved directly from an RNAase III recognition site. The deletions present in a number of T3 mutant strains and the location of the nucleotide changes in several T3 strains that are defective in their ability to grow on F+-containing strains or on optA mutant hosts have been determined. We discuss how T3 may have become genetically isolated from its relatives in the T7-T3 group and simultaneously acquired novel biological and biochemical properties.


Management Patterns of Hepatic Encephalopathy: A Nationwide Survey in India.
Hepatic encephalopathy (HE) is a common complication of cirrhosis. There is no standard practice for its management. This survey was done to determine the diagnostic and therapeutic practices of physicians treating patients with HE in patients with cirrhosis. We designed a 21-item questionnaire, which was given to physicians working in academic and non-academic institutes and regularly treating patients with HE. Of 500 printed questionnaires, we received 451 questionnaires [323 (72%) general physicians and 128 (28%) gastroenterologists] from academic and non-academic institutes. Commonest precipitating event of HE was upper gastrointestinal bleed (47%), constipation (18%) and spontaneous bacterial peritonitis (12%). Arterial ammonia was always measured at admission by 156 (35%) physicians, never measured by 128 (28%) and sometimes by 167 (37%). Prophylactic antibiotics were used by 54% of physicians on the day of admission irrespective of any precipitating event, and 13% used antibiotics only if cultures were positive while others used antibiotics only if patient needs intubation or had variceal bleed as the cause of precipitation of HE. Disaccharides remained the mainstay of treatment in the management of HE and were always used by 87% (n = 391) followed by LOLA (n = 297, 66%) and rifaximin (n = 276, 61%). Combination of therapy was used by 84% of respondents. Lactulose enema was used in patients with HE by 280 (62%) physicians and was thought to be as good as giving lactulose by mouth or nasogastric tube in the treatment of HE. Regarding the recovery of HE with the present mode of therapy, of 451 responses, only 11% (n = 49) got 90-100% response to present therapy for the recovery of HE, while 70-90% response was seen by n = 152 (34%) and 50-70% response was seen by n = 183 (41%). Lactulose was prescribed as secondary prophylaxis agent more by gastroenterologists than non-gastroenterologists (76% vs 41%, P = 0.001). Similarly, rifaximin was more prescribed by gastroenterologists at discharge compared to non-gastroenterologists (32% vs 17%, P = 0.001). Non-absorbable disaccharides are the most commonly prescribed treatment for HE and for secondary prophylaxis of HE. Combination of therapy (lactulose and LOLA or lactulose and rifaximin) was commonly used by treating physicians.


The State Urge to be Physically Active-Questionnaire (SUPA-Q): Development and validation of a state measure of activity urges in patients with eating disorders.
Many people, including patients with eating disorders (EDs), experience an increased urge for physical activity. "Trait"-like activity in patients with EDs is assessed by existing questionnaires, but there are few clinically validated assessments of a "state" urge to be physically active. Here, we developed and validated the State Urge to be Physically Active-Questionnaire (SUPA-Q). After developing and piloting the items, N = 126 patients with EDs (mostly anorexia nervosa and bulimia nervosa) took part in our mixed-longitudinal validation study with one primary assessment for all patients and a secondary assessment for a subsample of patients. Cronbach's α and split-half-methods served as measures of consistency and reliability. Correlations with other questionnaires were used to determine convergent and divergent validity, and confirmatory factor analysis was used for investigating factorial validity. We used paired-samples t-tests for repeated assessments to investigate change sensitivity. We found the SUPA-Q to be highly consistent, and reliable and to demonstrate convergent, divergent, and factorial validity. The comparison of SUPA-Q scores from repeated assessments within a subsample of patients demonstrated the questionnaire's change sensitivity, Cohen's d = 0.48. Moreover, an increase in SUPA-Q scores was associated with a less positive mood, more anxiety, more body dissatisfaction, more tenseness, less feelings of control, and more stress. The newly developed SUPA-Q may help to accentuate the necessity to evaluate and address the acute urge to engage in physical activity in patients with EDs in clinical practice and ultimately support tailoring treatments to patients' unique symptom patterns. The questionnaire is available at https://doi.org/10.17605/OSF.IO/G2YBC.


Apparent pKa shifts of titratable residues at high denaturant concentration and the impact on protein stability.
Urea and guanidine-hydrochloride (GdnHCl) are frequently used for protein denaturation in order to determine the Gibbs free energy of folding and kinetic folding/unfolding parameters. Constant pH value is applied in the folding/unfolding experiments at different denaturant concentrations and steady protonation state of titratable groups is assumed in the folded and unfolded protein, respectively. The apparent side-chain pKa values of Asp, Glu, His and Lys in the absence and presence of 6 M urea and GdnHCl, respectively, have been determined by 1H-NMR. pKa values of all four residues are up-shifted by 0.3-0.5 pH units in presence of 6 M urea by comparison with pKa values of the residues dissolved in water. In the presence of 6 M GdnHCl, pKa values are down-shifted by 0.2-0.3 pH units in the case of acidic and up-shifted by 0.3-0.5 pH units in the case of basic residues. Shifted pKa values in the presence of denaturant may have a pronounced effect on the outcome of the protein stability obtained from denaturant unfolding experiments.


All I need is the air that I breath: outdoor air quality and asthma.
In recent years, developing insight into the pathophysiology of asthma and advances in asthma management have been substantial. Despite these advancements, asthma remains a significant health problem in the paediatric population. In the USA, the prevalence of asthma in children under 18 years of age is estimated at 7% [US Environmental Health Protection Agency. Publication # EPA-100-r-018. Washington, DC, 2000]. Prevalence rates in various subpopulations, particularly African and Hispanic Americans, are much higher. Certain inner-city census tracts have estimated prevalence rates of 20 to 25% [ Crain EF Weiss KP, Stein REK. Pediatric 1994; 94: 356-362]. Many of these subpopulations experience alarmingly disparate and apparently increasing morbidity and mortality associated with asthma. Similar trends in prevalence and morbidity have been observed in urban populations outside the USA as well [Sears MR. Lancet 1997; 350: 1015-1020]. There is considerable controversy as to the scientific basis for these observed trends. While the identification of a single factor or even a closely related group of factors appears unlikely, there is considerable speculation about the role of environmental factors, particularly outdoor air quality. In the USA, the National Ambient Air Quality Standards (NAAQs) offer specific standards for air quality. These standards are applied to certain criteria pollutants, including ozone, particulate matter (both PM(10) and PM(2.5)), sulfur dioxide, nitrogen dioxide, lead and carbon monoxide [ Committee on Environmental Health, AAP. In: Handbook of Pediatric Environmental Health. Elk Grove Village, IL, 1999; 181-191]. The NAAQs were recently revised for both ozone and particulate matter based on data that suggested health risks existed at levels below those set forth in the previous standards. Monitoring data reveals that urban populations are more likely to be exposed to elevated levels of these pollutants [Dickey JH. Disease Monitor 2000; 46(9): 566-589]. Children are uniquely predisposed to the potential harmful effects of these pollutants. This predisposition is related to unique physiologic, anatomic and behavioural characteristics of the infant, child and adolescent. There is compelling evidence that an interplay of genetic predisposition and environmental exposure to a number of chemical and infectious agents may be operative in both the inception and persistence of the clinical asthma phenotype. The relative role of the criteria air pollutants in this interplay is the subject of considerable study. The potential value of intervention by regulatory agencies or by behavioural modification among individuals or communities should be explored. At the very least, the current data offers implications for situational strategies of asthma management based on local monitoring data.


Binding of heparin-dependent antibodies to PF4 modified by enoxaparin oligosaccharides: evaluation by surface plasmon resonance and serotonin release assay.
The minimal structural requirements of low-molecular-weight heparins that determine the risk of developing heparin-induced thrombocytopenia (HIT) are not fully defined. The ability of enoxaparin-derived oligosaccharides (OS) to induce platelet activation and exposure of platelet-factor 4 (PF4) epitopes recognized by antibodies developed in HIT was studied by surface plasmon resonance (SPR) and serotonin release assay. Decasaccharides with ≥ 11 sulfate groups induced platelet activation in the presence of plasma from patients with confirmed HIT. Serotonin release of > 80% without full inhibition at 100 μg mL(-1) was achieved with decasaccharides containing 14 or 15 sulfate groups, 2 dodecasaccharides and 2 tetradecasaccharides. An SPR method was developed using purified PF4 immobilized on carboxymethylated dextran. Antibodies from all HIT samples bound to PF4/heparin in SPR assays with resonance units (RU) ratio of 109-173 with HIT plasma vs. 88-93 with control plasma. RU ratios > 100 were measured when PF4 was pre-incubated with OS with ≥ 10 saccharide units and one octasaccharide containing 10 sulfate groups. RU ratios > 140, similar to those measured when PF4 was pre-incubated with unfractionated heparin or enoxaparin, were obtained with purified dodeca- and tetradecasaccharides. RU values strongly correlated with the number of sulfate groups in the decasaccharides tested (r = 0.93, P = 0.02). LMWHs with fragments > 10 saccharides and a large number of sulfate groups are more likely to be associated with a higher risk of HIT. These structure-activity relationships were independent of the ability of the OS to bind antithrombin.


Potentiation of morphine hyperthermia in cats by pimozide and fluoxetine hydrochloride.
Administration of morphine sulfate (1--4 mg/kg i.v.) to cats produces changes in body temperature, with hyperthermia appearing with larger doses. Since the central neurotransmitters dopamine and serotonin have been implicated in thermoregulation, studies were done to determine whether morphine's action could be mediated via these transmitters. Temperature responses were measured in freely moving cats by means of rectal thermometer probes. Either pimozide, 0.5 mg/kg i.p., a specific DA receptor blocker, or fluoxetine HCl, 10 mg/kg i.p., a specific inhibitor of 5-HT uptake, was administered 2--3 h prior to morphine injection. Temperatures were monitored for 3.5 h after morphine administration. Both agents were found to enhance the hyperthermic response to morphine with the maximum morphine effect occurring in most cases by 2 h. The results indicate that a balance in the ratio of 5-HT : DA may be involved in cat thermoregulation and that the hyperthermic response in the cat to morphine may be effected by shifting this 5-HT : DA ratio.


Electrosynthesis of polypyrrole on steel fiber for solid-phase microextraction of citalopram in serum.
A solid-phase microextraction (SPME) technique using steel fiber coated with polypyrrole (PPY) was developed for UV-Vis determination of citalopram in blood serum. The coating was prepared using a three-electrode electrochemical system from an acetonitrile/aqueous (ACN/H(2)O) oxalic acid solution containing 0.01 M of pyrrole monomer by applying a potential range (0-1.3 V) for 25 min. In order to obtain an efficient film of PPY, experimental parameters related to the coating process were optimized, specifically deposition potential, concentration of monomer, and number of cycles. The effects of various parameters on the efficiency of the SPME process such as extraction time, stirring speed, adsorption and desorption temperature, desorption solvent, and pH of desorption solution were also studied. The coating was stable and adhered to the surface of the steel fiber. The method was linear over about three orders of magnitude with an average correlation coefficient of 0.97. Spiking of blank samples with 0.2 μg/mL citalopram afforded a recovery of 84% with a precision of 10.2%. A limit of detection of 0.046 μg/mL (based on S/N = 3) was obtained in the linear dynamic range of 0.046-2.0 μg/mL. The proposed method was applied to monitor citalopram in serum samples.


Multi-Toxic Endpoints of the Foodborne Mycotoxins in Nematode Caenorhabditis elegans.
Aflatoxins B₁ (AFB₁), deoxynivalenol (DON), fumonisin B₁ (FB₁), T-2 toxin (T-2), and zearalenone (ZEA) are the major foodborne mycotoxins of public health concerns. In the present study, the multiple toxic endpoints of these naturally-occurring mycotoxins were evaluated in Caenorhabditis elegans model for their lethality, toxic effects on growth and reproduction, as well as influence on lifespan. We found that the lethality endpoint was more sensitive for T-2 toxicity with the EC50 at 1.38 mg/L, the growth endpoint was relatively sensitive for AFB₁ toxic effects, and the reproduction endpoint was more sensitive for toxicities of AFB₁, FB₁, and ZEA. Moreover, the lifespan endpoint was sensitive to toxic effects of all five tested mycotoxins. Data obtained from this study may serve as an important contribution to knowledge on assessment of mycotoxin toxic effects, especially for assessing developmental and reproductive toxic effects, using the C. elegans model.


Modeling banana uptake of pesticides by incorporating a peel-pulp interaction system into a multicompartment fruit tree model.
According to field research, banana peels have a significant impact on the uptake of pesticide residues by banana pulps. To predict pesticide residue concentrations in harvested bananas, however, current modeling approaches did not take into consideration the banana peel as a single simulating compartment. To address the problem, we incorporated a peel-pulp interaction system into a modified multicompartment fruit tree model in order to simulate pesticide residue concentrations in banana plants. The simulation results revealed that lipophilicity played a crucial role in regulating pesticide bioaccumulation in banana plants, showing that moderately- or highly-lipophilic compounds had a high potential for bioaccumulation in banana pulps and peels. Some model inputs, such as peel thickness, degradation rates in plant tissues, and dissipation rates in the soil, had a substantial impact on the bioaccumulation of pesticides in banana pulps and peels. Even if more aspects (such as dynamically morphological properties of banana plants and ionizable chemical compounds) must be considered for in future research, the proposed modeling approach can aid in the comprehension of the pesticide bioaccumulation mechanism in banana plants.


Hemophagocytic syndrome following haploidentical peripheral blood stem cell transplantation with post-transplant cyclophosphamide.
Hemophagocytic syndrome (HPS) is a rare but serious complication after allogeneic transplantation which has been reported to be particularly high after unrelated cord blood transplantation. We report on the incidence, risk factors and outcome of HPS in 51 patients (age 2-64 years) after haploidentical peripheral blood stem cell (PBSC) transplantation with post-transplantation cyclophosphamide (PTCY). The incidence of HPS was 12.2 %, occurring at a median of 18 days. The non-relapse mortality in patients with HPS was 83.3 % compared to 11.6 % in patients without HPS. Complete donor chimerism was documented in all patients with HPS. Definite infective etiology was identified in two patients only. The others were refractory to multiple lines of treatment and 3 patients underwent a second transplant. Even though the symptoms and biochemical markers of HPS showed prompt response in 2/3 patients undergoing a second allograft, they succumbed to infections before haematological recovery. The others succumbed to multi-organ failure or infections. Age < 10 years, transplantation for non-malignant disease and high CD34 content of the graft were identified as risk factors for HPS. Considering the fact that post-transplant HPS is usually a refractory and fatal condition, we discuss further attempts at deciphering the pathogenesis, developing modalities to prevent this complication and improve the outcome.


Detection of the carrier state for an X-linked disorder, the Lesch-Nyhan syndrome, by the use of lymphocyte cloning.
Using a limiting dilution technique, we found that the frequency of thioguanine resistant (TGR) lymphocyte clones was less than 5.0 X 10(-5) in 14 normal individuals, between 9.0 X 10(-3) and 8.9 X 10(-2) in seven heterozygotes for Lesch-Nyhan syndrome, and 0.88 and 0.87 in two hemizygotes. TGR clones from heterozygotes were expanded and had the hemizygote phenotype as evidenced by low hypoxanthine incorporation and severely deficient hypoxanthine-guanine-phosphoribosyl-transferase activity. Enumeration of TGR lymphocyte clones provides a simple technique for detection of heterozygosity for Lesch-Nyhan syndrome. A similar approach using lymphocyte cloning may be suitable for detection of the carrier state for other X-linked disorders.


Recent advances in synthesis of sugar and nucleoside coumarin conjugates and their biological impact.
Naturally occurring coumarin and sugar molecules have a diverse range of applications along with superior biocompatibility. Coumarin, a member of the benzopyrone family, exhibits a wide spectrum of medicinal properties, such as anti-coagulant, anti-bacterial, anti-tumor, anti-oxidant, anti-cancer, anti-inflammatory and anti-viral activities. The sugar moiety functions as the central scaffold for the synthesis of complex molecules, attributing to their excellent biocompatibility, well-defined stereochemistry, benign nature and outstanding aqueous solubility. When the coumarin moiety is conjugated with the sugar or nucleoside molecule, the resulting conjugates exhibit significant biological properties. Due to the remarkable growth of such bioconjugates in the field of science over the last decade, owing to their future prospect as a potential bioactive core, an update to this area is very much needed. The present review focusses on the synthesis, characterization and the various therapeutic applications of coumarin conjugates, i.e., sugar and nucleoside coumarin conjugates along with their perspective for future research.


Impact of calcium peroxide dosage on the control of nutrients release from sediment in the anoxic landscape water.
The anoxic and reductive aquatic environment is formed easily in summer due to the global warming, which may accelerate endogenous release. In this experiment, four different dosages of calcium peroxide (CaO2) were adopted to study the control effects of nutrients release from the sediments in the simulated landscape waters. The results demonstrated that CaO2 addition could effectively improve the physicochemical properties and microbial composition in sediments, and an obvious improvement was achieved with a larger dosage. It was observed that the surface sediments of experiment groups were oxidized to form a capping barrier between the sediment and overlying water, which might cut off the pollutant diffusion in sediment. Meanwhile, CaO2 could decrease the nutrients concentration in water obviously, and the reduced effect was positively correlated with the CaO2 dosage. Compared with the nutrients release fluxes in CK (105.89 mg-TN m-2 day-1, 106.48 mg-NH4+-N m-2 day-1, 4.14 mg-TP m-2 day-1, and 4.30 mg-SRP m-2 day-1), the CaO2 dosages of 0.12 and 0.18 kg m-2 could entirely inhibit the nutrients release from sediment, and partially reduce the original pollutants in the overlying water. However, 0.18 kg m-2 CaO2 would cause a higher increase of pH value and NO2--N concentration, and bring potential risk to the aquatic ecosystem. Therefore, 0.12 kg-CaO2 m-2-sediment was selected as the optimal dosage by considering the control effect, economic cost, and potential risk comprehensively. In general, this study provided a quantitative usage method of CaO2, which is convenient and effective to prevent or control the nutrients release from sediment caused by anoxic and reductive condition in summer.


Segmental deficiency of cervical tracheal rings masquerading as complete tracheal rings: A case report and literature review.
Congenital deficiency of distal tracheal rings is a rare anomaly and has been previously reported in the literature. Here we report the first case deficient tracheal rings confined to the cervical trachea. Patient was transferred to our institution for management of what was initial thought to be complete tracheal rings. The patient was successfully managed with a tracheal resection and short segment cervical slide tracheoplasty. Presentation, surgical approach, histological findings, and literature review are described.


Association between lifestyle modifications and improvement of early cardiac damage in children and adolescents with excess weight and/or high blood pressure.
It is not known whether, in children and adolescents with alterations in weight and/or blood pressure (BP), lifestyle modifications are associated with an improvement of early cardiac damage. In a pediatric population referred for excess weight, high BP, or both (n = 278, 10.6 (2.3) years), echocardiography was performed at enrollment and after 15 months of follow-up, during which participants received nonpharmacological treatment, based on correcting unhealthy lifestyles and improving dietary habits. Left ventricular mass was indexed for height (g/m2.7, LVMI), and an LVMI value higher than or equal to age- and gender-specific 95th percentile was the criterion for defining left ventricular hypertrophy (LVH). Multiple linear and logistic regression analyses were carried out to determine associations between changes in BMI and BP z-scores and changes of LVMI values and LVH prevalence, from baseline to follow-up. At baseline, 33.1% of study participants were hypertensive, 52.9% obese, and 36.3% had LVH. At follow-up, the prevalence of hypertension, obesity, and LVH was 18.7%, 30.2%, and 22.3%, respectively (p < 0.001 for all). A decrease in LVMI from 37.1 to 35.2 g/m2.7 (p < 0.001) was observed. Only delta BMI z-score positively related to an improvement of LVMI. Reductions of BMI (OR = 0.22, 95% CI 0.07-0.64) and diastolic BP (OR = 0.64, 95% CI 0.42-0.93) z-scores from baseline to follow-up and family history of hypertension (OR = 0.36, 95% CI 0.16-0.78) were associated with a lower prevalence of LVH. In a pediatric population at cardiovascular risk, changing incorrect lifestyle and dietary habits is associated with both reduction of BMI and BP values and regression of early cardiac damage. A higher resolution version of the Graphical abstract is available as Supplementary information.


Perceived control and emotional status in abusive college student relationships: an exploration of gender differences.
The authors assessed perceived control, dysphoria, hopelessness, self-esteem, and optimism in 280 college students involved in abusive and nonabusive relationships. Women reported higher levels of dysphoria and lower levels of self-esteem and optimism than men. Women in abusive relationships reported more psychological symptoms than men in abusive relationships. After controlling for gender differences in emotional status, participants in abusive relationships showed more psychological symptoms than those in nonabusive relationships. Women showed lower perceived control of relationship conflicts than men. Men experiencing high levels of abuse reported higher perceived control of relationship conflict than females experiencing low levels of abuse. Perceived control was affected more by gender than emotional status, abuse level, and gender-affected emotional status. The authors discuss the results in terms of their implications for future investigations of emotional reactions to abuse.


Late free-flap salvage with catheter-directed thrombolysis.
Despite high success rates with free-tissue transfer, flap loss continues to be a devastating event. Flap salvage is often successful if vascular complications are recognized and treated early. However, delayed presentation of flap compromise is an ominous predictor of flap loss. Late free-flap salvage has been described with poor long-term results. Catheter-directed thrombolysis (CDT) has only been described in context with free-tissue transfer in a case of distal bypass salvage. The authors examined the efficacy of highly selective CDT in late salvage of free-flaps with vascular compromise. Two patients underwent highly selective CDT after delayed presentation (>5 days) of flap compromise. Patient 1 is a 59-year-old woman who underwent delayed breast reconstruction with a free TRAM flap and presented with arterial thrombosis 12 days postoperatively. Patient 2 is a 53-year-old man who underwent fibular osteocutaneous free-flap reconstruction of a floor of mouth defect who developed venous thrombosis 6 days postoperatively. Patient 2 underwent two attempted operative anastamotic revisions with thrombectomies and local thrombolysis prior to CDT. The average time of presentation was 9 days, with the average time to CDT being 9.5 days. Patient 1 had an arterial thrombosis, whereas Patient 2 had a venous thrombosis. Both patients underwent successful thrombolysis after super-selective angiograms. Continuous infusions of thrombolytic agents were used in both patients for approximately 24 h. Average length of stay postCDT was 7 days with no perioperative complications. Long-term follow-up demonstrated complete flap salvage with no soft tissue loss. Despite extremely delayed presentation, aggressive CDT was successful in both breast, and head and neck reconstructions with excellent long-term flap results. CDT appears to be a useful modality in managing difficult cases of free-flap salvage.


Clinical significance of panendoscopy in initial staging of oral squamous cell carcinoma and detection of synchronous second malignancies of the upper aerodigestive tract - Insights from a retrospective population-based cohort study.
The aim of this study was to examine the prevalence of synchronous upper aerodigestive tract (UAT) tumors within oral squamous cell carcinoma (OSCC) patients, and to specify distinct risk groups who benefit from panendoscopy. Definite clinical and pathohistological characteristics, as well as overall and recurrence-free survival (OAS and RFS, respectively) of OSCC patients with and without synchronous second UAT tumors, carcinomas in situ, or higher-grade dysplasia/metaplasia, were evaluated based on a retrospective population-based cohort study, including alignment with cancer registry data. Out of 727 included OSCC patients, 465 cases (64.0%) received panendoscopy. Among these, 18 UAT tumors were detected, all of which were linked to patients with a positive history of nicotine abuse. Every synchronous UAT tumor was revealed by panendoscopy, which, analyzed as an independent staging procedure, was accompanied by a low complication rate (1.7%). When illuminating the impact of a second UAT tumor in OSCC patients, survival analysis revealed reduced 5-year OAS (63.9% vs 43.5%, p = 0.010) and RFS (57.1% vs 32.4%, p = 0.016) for patients with a second oncology diagnosis of the UAT. Within the limitations of the study, it seems that panendoscopy should be performed in the majority of patients suffering from OSCC, because most of them have a history of smoking and drinking, which correlates with an increased risk of developing synchronous UAT tumors.


PMI's own in vivo clinical data on biomarkers of potential harm in Americans show that IQOS is not detectably different from conventional cigarettes.
New 'heated tobacco products' are being marketed in several countries with claims that they expose users to lower levels of toxins than conventional cigarettes which could be read as being less likely to cause health problems than conventional cigarettes. In the USA, Philip Morris International (PMI) has submitted an application to the Food and Drug Administration for permission to market its heated tobacco product, IQOS, with reduced exposure and reduced risk claims. Analysis of detailed results on 24 biomarkers of potential harm in PMI studies of humans using IQOS compared with humans using conventional cigarettes. Among American adults, there is no statistically detectable difference between IQOS and conventional cigarette users for 23 of the 24 biomarkers of potential harm in PMI's studies. In Japan, there were no significant differences between people using IQOS and conventional cigarettes in 10 of 13 biomarkers of potential harm. It is likely that some of the significant differences are false positives. Despite delivering lower levels of some toxins than conventional cigarettes, PMI's own data fail to show consistently lower risks of harm in humans using its heated tobacco product, IQOS, than conventional cigarettes.


Healthcare Organizations Management: Analyzing Characteristics, Features and Factors, to Identify Gaps "Scoping Review".
Studying the organizational characteristics, factors and features in healthcare organizations will have its prompt in achieving the desired outcomes of the provided services. Addressing these variables, the subsequent study conducts a scoping review methodology to systematically evaluate existing information while focusing on conclusions and gaps representing organizational variables that have been shown to influence the management of healthcare organizations. A scoping review was performed to shed the light on the healthcare organizations' characteristics, features and factors. Fifteen articles were included in the final analysis of this study. Among the relevant studies, 12 were research articles and 8 were quantitative studies. Continuity of care, organizational culture, patient trust, strategic factors and operational factors are among the explored features that have an impact in the management of healthcare organizations. This review shows the gaps in the management practice and in the management studies that address healthcare organizations.


Deep learning model predicts water interaction sites on the surface of proteins using limited-resolution data.
We develop a residual deep learning model, hotWater (https://pypi.org/project/hotWater/), to identify key water interaction sites on proteins for binding models and drug discovery. This is tested on new crystal structures, as well as cryo-EM and NMR structures from the PDB and in crystallographic refinement with promising results.


The turtle carapace as an optimized multi-scale biological composite armor - A review.
The turtle carapace, the top dorsal part of the shell, is a remarkable multi-scale dermal armor that has evolved to withstand various types of high-stress events encountered in nature. This keratin-covered boney exoskeleton exhibits a number of structural motifs, including alternating rigid and flexible components, layering and functionally graded elements, designed to protect the reptile during predatory attacks, and smashing events. Here we review the multi-scale structural hierarchy of the turtle carapace and its corresponding mechanical properties. We show how the microscopic features of the carapace govern its various macroscopic mechanical responses relevant to protective functioning, including dynamic (impact and cyclic) compression and bending loading situations. In addition, the effect of hydration, a crucial factor for proper physiological-mechanical behavior of biological materials, is illustrated throughout. We also discuss carapace-inspired designs that could be advantageous over the traditional strategies adopted in impact-resistant materials, and could bring new mechanistic insights.


Investigation of monitoring for internal exposure by urine bioassay in a biomedical research facility.
A simple monitoring programme by urine bioassay was carried out to assess internal doses for workers in a biomedical research facility. Urine samples were measured without chemical treatment using a liquid scintillation counter or sodium iodide (NaI (Tl)) scintillation detector. The detection limits for the committed effective doses were below 1 mSv for 125I and 131I and below 1 x 10(-1) mSv for 3H, 14C, 32P, 35S and 51Cr, in the case that samples were collected within 3 d after handling. All of the urinary concentrations were below the detection limit, suggesting that no significant intake was detected during the investigation. The present results suggest that personal monitoring, such as the urine bioassay, is not necessary in many cases as a routine monitoring for workers engaged in tracer experiments using the above nuclides.


Effect of low-level laser therapy on healing of tenotomized Achilles tendon in streptozotocin-induced diabetic rats.
Diabetes mellitus (DM) is associated with musculoskeletal damage. Investigations have indicated that healing of the surgically tenotomized Achilles tendon was considerably augmented following low-level laser therapy (LLLT) in non-diabetic, healthy animals. The aim of the present study was to evaluate the effect of LLLT on the Achilles tendon healing in streptozotocin-induced diabetic (STZ-D) rats via a biomechanical evaluating method. Thirty-three rats were divided into non-diabetic (n = 18) and diabetic (n = 15) groups. DM was induced in the rats by injections of STZ. The right Achilles tendons of all rats were tenotomized 1 month after STZ injections. The two experimental groups (n = 6 for each group) of non-diabetic rats were irradiated with a helium-neon (He-Ne) laser at 2.9 and 11.5 J/cm(2) for ten consecutive days. The two experimental groups of diabetic rats (n = 5 for each group) were irradiated with a He-Ne laser at 2.9 and 4.3 J/cm(2) for ten consecutive days. The tendons were submitted to a tensiometric test. Significant improvements in the maximum stress (MS) values (Newton per square millimeter) were found following LLLT at 2.9 J/cm(2) in both the non-diabetic (p = 0.031) and diabetic (p = 0.019) experimental groups when compared with their control groups. LLLT at 2.9 J/cm(2) to the tenotomized Achilles tendons in the non-diabetic and diabetic rats significantly increased the strength and MS of repairing Achilles tendons in our study.


Recommendations for the use of propensity score methods in multiple sclerosis research.
With many disease-modifying therapies currently approved for the management of multiple sclerosis, there is a growing need to evaluate the comparative effectiveness and safety of those therapies from real-world data sources. Propensity score methods have recently gained popularity in multiple sclerosis research to generate real-world evidence. Recent evidence suggests, however, that the conduct and reporting of propensity score analyses are often suboptimal in multiple sclerosis studies. To provide practical guidance to clinicians and researchers on the use of propensity score methods within the context of multiple sclerosis research. We summarize recommendations on the use of propensity score matching and weighting based on the current methodological literature, and provide examples of good practice. Step-by-step recommendations are presented, starting with covariate selection and propensity score estimation, followed by guidance on the assessment of covariate balance and implementation of propensity score matching and weighting. Finally, we focus on treatment effect estimation and sensitivity analyses. This comprehensive set of recommendations highlights key elements that require careful attention when using propensity score methods.


[One-year effect of health counseling on life style and risk factors of heart disease].
We examined the need for counselling and the effect on willingness and ability to change life-style, and subsequent changes in risk factors for CHD. All 152 male employees in a computer company, 25-45 years of age, were invited to participate in a controlled intervention study over one year. The subjects were randomised to an intervention group (I group) and a control group. The I group was divided into subgroups based on baseline behaviour and risk factor status. Changes were evaluated after one year. After an initial health examination, participants in the I group were counselled at baseline and at 5 months. Eighty-five (56%) men participated. Twenty-nine were assigned to a control group and 56 to an intervention group (I group) (dropouts = 8). An exercise group (E group) was advised to take up aerobics exercise three times/week, a diet group to reduce the intake of saturated fat and increase fish products, and smokers to stop smoking. Forty were recommended one or more behavioural changes and eight had no need. Thirty-four were willing to make behavioural changes. Compared to the control group, the fitness level increased (p < 0.01) and body weight decreased in the I group (p < 0.05). Individual counselling promotes regular exercise with subsequent improvements in CHD risk factors. The diet and smoking counselling models were less successful in terms of compliance.


Synthesis and biological evaluation of novel 2-azido muramyl dipeptide as NOD2 agonistic adjuvants.
Novel 2-Azido muramyl dipeptide was synthesized by the bio-isosteric replacement of the N-acetyl group of the muramic acid fragment with the azide functionality at the C2 position. In order to examine the effect of hydrophilic-lipophilic balance on the adjuvant activity, derivatives were synthesized by removing protecting groups sequentially to tune the polarity. Amongst five novel azido derivatives of MDP studied here, di- and mono-benzylated azido derivatives 10 and 11 exhibited good DENV specific antibody(IgG) response with Th1 polarization compared to parent compound Muramyl dipeptide (MDP) whereas all five new derivatives responded positively to NOD2 agonistic assays with compound 10 showing highest stimulation.


MicroRNA-143 and -145 modulate the phenotype of synovial fibroblasts in rheumatoid arthritis.
Fibroblast-like synoviocytes (FLSs) constitute a major cell subset of rheumatoid arthritis (RA) synovia. Dysregulation of microRNAs (miRNAs) has been implicated in activation and proliferation of RA-FLSs. However, the functional association of various miRNAs with their targets that are characteristic of the RA-FLS phenotype has not been globally elucidated. In this study, we performed microarray analyses of miRNAs and mRNAs in RA-FLSs and osteoarthritis FLSs (OA-FLSs), simultaneously, to validate how dysregulated miRNAs may be associated with the RA-FLS phenotype. Global miRNA profiling revealed that miR-143 and miR-145 were differentially upregulated in RA-FLSs compared to OA-FLSs. miR-143 and miR-145 were highly expressed in independent RA-FLSs. The miRNA-target prediction and network model of the predicted targets identified insulin-like growth factor binding protein 5 (IGFBP5) and semaphorin 3A (SEMA3A) as potential target genes downregulated by miR-143 and miR-145, respectively. IGFBP5 level was inversely correlated with miR-143 expression, and its deficiency rendered RA-FLSs more sensitive to TNFα stimulation, promoting IL-6 production and NF-κB activity. Moreover, SEMA3A was a direct target of miR-145, as determined by a luciferase reporter assay, antagonizing VEGF165-induced increases in the survival, migration and invasion of RA-FLSs. Taken together, our data suggest that enhanced expression of miR-143 and miR-145 renders RA-FLSs susceptible to TNFα and VEGF165 stimuli by downregulating IGFBP5 and SEMA3A, respectively, and that these miRNAs could be therapeutic targets.


Early protected weight bearing in African patients with fractures of the femur.
Among 100 cases of closed fracture of the femur admitted to a Nigerian hospital during the years 1954--71, and treated by skin or skeletal traction, the mean time to clinical union was 6 weeks and to discharge on protected weight bearing 7 weeks. There were no cases on non-union. It is suggested that the traditional recommendation of 12-14 weeks in traction to ensure clinical union of a fracture of the femur should be revised, at least in African patients.


Management of Spinal Metastasis by Minimally Invasive Surgical Techniques: Surgical Principles and Indications-A Literature Review.
Spinal metastasis is becoming more frequent. This raises the topics of pain and neurological complications, which worsen the functional and survival prognosis of oncological population patients. Surgical treatment must be as complete as possible in order to decompress and stabilize without delaying the management of the oncological disease. Minimally invasive spine surgical techniques inflict less damage on the musculocutaneous plan than opened ones. Different minimally invasive techniques are proposed in this paper for the management of spinal metastasis. We used our experience, developed degenerative and traumatic pathologies, and referred to many authors, establishing a narrative review of our local practice. Forty-eight articles were selected, and these allowed us to describe the different techniques: percutaneous methods such as vertebro/kyphoplasty, osteosynthesis, mini-open surgery, or that through a posterior or anterior approach. Also, some studies detail the contribution of new technologies, such as intraoperative CT scan and robotic assistance. It seems essential to offer a lasting solution to a spinal problem, such as in the form of pain relief, stabilization, and decompression. Our department has embraced a multidisciplinary and multidimensional approach to MISS, incorporating cutting-edge technologies and evidence-based practices.


Laryngotracheal involvement in epidermolysis bullosa.
Epidermolysis bullosa (EB) is a rare hereditary skin disease of infancy that can involve the mucous membranes of the oral cavity. Laryngotracheal involvement is rare. The disease is characterized by bullae formation in response to minor trauma. There are at least 18 described types of EB, however, there are 3 basic categories. These are simplex (with disruption above the basement membrane), dystrophic (in which disruption is below the basement membrane), and junctional (in which the split is within the lamina lucida). The prognosis of the different types ranges from early death usually secondary to overwhelming sepsis, to long term survivals with lack of growth retardation or significant dystrophic scarring. Presently, survival appears to be the only reliable criteria for distinguishing the benign and lethal forms of EB. Airway obstruction secondary to laryngotracheal involvement should be considered in any child with epidermolysis bullosa presented with symptoms of respiratory distress. Because there are few predictive prognostic indicators in the neonatal period, tracheotomy should be considered early in an effort to prevent further laryngeal injury from intubation, in those patients that will survive.


Bilateral mucosal flap septal perforation repair in the adolescent.
Perforations of the nasal septum are rare in the pediatric age group. High success rates for attempted perforation closure utilizing mucosal flap techniques in adults are frequently reported. This study reviews our experience with pediatric patients diagnosed with a septal perforation who underwent attempted closure during adolescence. Our endonasal bilateral mucosal flap technique is present. This study is an observational case series with retrospective chart review of a single surgeon's experience of attempted septal perforation repair utilizing bilateral mucosal flaps with an interposition graft in patients diagnosed with a perforation prior to age 19. The study period was from November 1991 to April 2019. Patient demographics, perforation characteristics (etiology, symptoms and size), surgical closure technique and outcomes are presented. Twenty-three patients (13 females) met the study criteria. Mean age at diagnosis was 14.3 (range, 3-18) years. Crusting (82.6%), nasal obstruction/congestion (60.9%) and epistaxis (47.8%) were the most frequent reported symptoms at presentation. Fourteen patients who underwent attempted closure during adolescence had a minimum of three months follow-up. Mean age at the time of bilateral mucosal flap repair was 17.4 (range, 13-19) years. Mean perforation length was 14.2 (range, 8-22) mm and mean height 10.6 (range, 5-15) mm. Complete closure was noted in all but one patient (92.8%) at the time of last follow-up, mean 16.9 (range, 3-92) months. Every patient noted partial to complete resolution in presenting symptoms. Four patients required revision surgery to address persistent postoperative obstruction. Our experience demonstrates septal perforation repair utilizing a bilateral mucosal flap technique can be successfully employed in the adolescent patient.