Blink recovery in patients with Bell's palsy: a neurophysiological and behavioral longitudinal study.
To examine the recovery process of blinking in a longitudinal study of nine patients severely affected by Bell's palsy. Kinematics of bilateral eyelid and eye movements and concomitant orbicularis oculi activity during voluntary blinking and air-puff- and acoustic-click-induced reflex blinking were determined by using the magnetic search coil technique and electromyographic recording of the orbicularis oculi muscle (OO-EMG). In the first 3 months of absence of OO-EMG activity, reduced eyelid and eye movement of the palsied eyelid were observed during all types of blinking. First OO-EMG activity was determined 3 months after onset of the affliction. After 1 year, OO-EMG activity was normalized and showed values similar to those on the nonpalsied side. Clinically, eyelid movements were normal after 1 year, although corresponding maximum amplitudes and corresponding velocities were two times smaller, expressed in reduced eyelid motility. Directions of eye movement during reflex blinking were normal after 1 year, although maximum amplitudes were smaller on the palsied side. Eye movements during voluntary blinking remained impaired. A simultaneous horizontal upward shift of both eyes in the same direction was recorded throughout the study. Although OO-EMG activity on the palsied side was normalized 1 year after onset of the affliction, the accompanying eyelid movements and their maximum amplitudes and velocities remained smaller throughout the study. The consistent impairment of eye movements in voluntary blinking during the study and reduced motility of eyelid movements indicates that higher brain structures, which modify eyelid and eye movement control during blinking, may be altered by the affliction.


Viscosity and surface tension of dilute salicylic acid-cetrimide systems.
The viscosity and surface tension of systems containing small amounts of salicylic acid in aqueous solutions of cetrimide were determined. An abrupt increase in viscosity was observed, and the molar ratio of salicylic acid to certrimide at which this viscosity increase occurred was 1:2. The surface tension of these systems also increased sharply after an initial lowering. The salicylic acid concentration at which this behavior was demonstrated was almost the same as that at maximum solubility in the surfactant solution.


The Impact of the Introduction of MELD on the Dynamics of the Liver Transplantation Waiting List in São Paulo, Brazil.
Until July 15, 2006, the time on the waiting list was the main criterion for allocating deceased donor livers in the state of São Paulo, Brazil. After this date, MELD has been the basis for the allocation of deceased donor livers for adult transplantation. Our aim was to compare the waitlist dynamics before MELD (1997-2005) and after MELD (2006-2012) in our state. A retrospective study was conducted including the data from all the liver transplant candidate waiting lists from July 1997 to December 2012. The data were related to the actual number of liver transplantations (Tr), the incidence of new patients on the list (I), and the number of patients who died while being on the waitlist (D) from 1997 to 2005 (the pre-MELD era) and from 2006 to 2012 (the post-MELD era). The number of transplantations from 1997 to 2005 and from 2006 to 2012 increased nonlinearly, with a clear trend to levelling to equilibrium at approximately 350 and 500 cases per year, respectively. The implementation of the MELD score resulted in a shorter waiting time until liver transplantation. Additionally, there was a significant effect on the waitlist dynamics in the first 4 years; however, the curves diverge from there, implying a null long-range effect on the waitlist by the MELD scores.


Toward standardization of BK virus monitoring: evaluation of the BK virus R-gene kit for quantification of BK viral load in urine, whole-blood, and plasma specimens.
Screening of BK virus (BKV) replication is recommended to identify patients at increased risk of BKV-associated diseases. However, the heterogeneity of molecular techniques hinders the establishment of universal guidelines for BKV monitoring. Here we aimed to compare the performance of the CE-marked BK virus R-gene kit (R-gene) to the performance of our in-house assay for quantification of BKV DNA loads (BKVL). A 12-specimen panel from the Quality Control for Molecular Diagnostics (QCMD) organization, 163 urine samples, and 88 paired specimens of plasma and whole blood (WB) from transplant recipients were tested. Both the R-gene and in-house assays showed a good correlation within the QCMD panel (r = 0.995 and r = 0.989, respectively). BKVL were highly correlated between assays, although positive biases were observed with the in-house assay in analysis of urine (0.72 ± 0.83 log10 copies/ml), plasma (1.17 ± 0.63 log10 copies/ml), and WB (1.28 ± 0.37 log10 copies/ml). Recalibration with a common calibrator significantly reduced the bias in comparisons between assays. In contrast, BKVL was underestimated with the in-house PCR in eight samples containing BKV genotype II, presenting point mutations at primer-annealing sites. Using the R-gene assay, plasma and WB specimens were found to be equally suitable for quantification of BKVL, as indicated by the high correlation coefficient (r = 0.965, P < 0.0001). In conclusion, the R-gene assay demonstrated reliable performance and higher accuracy than the in-house assay for quantification of BKVL in urine and blood specimens. Screening of BKV replication by a well-validated commercial kit may enable clinical laboratories to assess viral loads with greater reproducibility and precision.


Predictive value of HbA1c for in-hospital adverse prognosis in COVID-19: A systematic review and meta-analysis.
Clinical and laboratory predictors of adverse clinical course and death in COVID-19 patients urgently need to be identified. So far, the association between HbA1c and in-hospital mortality of COVID-19 remains a controversial issue. The aim of this study is to analyze predictive value of HbA1c for adverse prognosis in COVID-19. Both Chinese and English databases were systematically searched using specific keywords associated with the aims until November 21th, 2020. The Newcastle-Ottawa Scale (NOS) was used for quality assessment. A Statistical analysis was carried out using Review Manager 5.3 and STATA 15.1. Nine clinical trials were included in this study involving 2577 subjects. The results indicate that the association between elevated HbA1c referred as a continuous variable and adverse prognosis of COVID-19 was not significant (OR, 1.02; 95%CI, 0.95-1.09). However, higher HbA1c levels regarded as a dichotomous variable contributed to an increase mortality of COVID-19 (OR, 2.300; 95%CI, 1.679-3.150). Results were stable in a sensitivity analysis. More studies are needed to demonstrate the effect of HbA1c on hospital mortality. Prolonged uncontrolled hyperglycemia increases the risk of adverse prognosis in COVID-19. Patients with higher HbA1c should be monitored strictly to minimize the risk of adverse prognosis in COVID-19.


Anderson localization of solitons.
At low temperature, a quasi-one-dimensional ensemble of atoms with an attractive interaction forms a bright soliton. When exposed to a weak and smooth external potential, the shape of the soliton is hardly modified, but its center-of-mass motion is affected. We show that in a spatially correlated disordered potential, the quantum motion of a bright soliton displays Anderson localization. The localization length can be much larger than the soliton size and could be observed experimentally.


Influence of quantity of lymph-vascular space invasion on the risk of nodal metastases in women with early-stage squamous cancer of the cervix.
To determine if the quantity of lymph-vascular space invasion influences the risk of pelvic nodal metastases in women with early-stage cervical squamous carcinoma. Between 1991 and 1997, 105 women with stages IA2, Ib, and IIa squamous carcinoma of the cervix underwent radical hysterectomy and pelvic lymphadenectomy. The histopathology slides were prospectively reviewed. If lymph-vascular space invasion (LVSI) was present, the amount was quantified in four ways: percentage of cervical histopathologic sections containing LVSI, percentage of sections with tumor containing LVSI, total number of foci of LVSI, and maximal number of foci of LVSI in 10 high-powered fields. These measures of LVSI were correlated with the risk of nodal metastases. Seventy-three (70%) women had tumors with LVSI. Of these, 23 had pelvic nodal metastases. All women with nodal metastases had tumors with LVSI. Using logistic regession, independent predictors of nodal metastases were depth of cervical stromal invasion (P = 0.01) and tumor size (P = 0.04). LVSI was also a significant predictor of nodal metastases based on the Mantel-Haenszel test (P = 0.01). In women whose tumors contained LVSI, logistic regression identified tumor size (P = 0.004) and LVSI in > 45% of all cervical histopathologic sections (P = 0.002) as significant predictors of nodal metastases. The quantity of LVSI, as defined by the percentage of all cervical histopathologic sections containing LVSI, correlates significantly with the risk of nodal metastases in women with early-stage squamous carcinoma of the cervix.


Visual outcome of 25 Gauge vitrectomy for acute post operative infectious endophthalmitis.
The correlation between the change in foveal thickness measured using optical coherence tomography (OCT) following surgery for infectious endophthalmitis and preoperative and postoperative visual acuity is uncertain, and there are few pertinent studies on this topic. We explored the variations in macular thickness using OCT after emergency vitrectomy for post-cataract infectious endophthalmitis and the relationship between macular thickness with changes in visual function. We included 10 cases of post-cataract infectious endophthalmitis. Each patient underwent 25-G vitrectomy. The infection in all 10 patients was under control and visual function improved. Postoperative vitreous humor culture was positive in 8 patients, including 7 cases of coagulase-negative Staphylococcus epidermidis and 1 case of Lactobacillus acidophilus. The average age of these 10 patients was 71.60 ± 8.71 years (P< 0.05, two-tailed). There was no significant correlation between time 2 (the time of onset after cataract surgery) and visual prognosis. The average time 1 (the time of the vitrification surgery caused by the onset of the disease) was 1.45 ± 0.76 days (P< 0.05, two-tailed). The postoperative 3dVA ranged from 0.20 to 3.00, with an average visual acuity of 1.87 ± 1.12, which was superior to the preoperative value (P< 0.01, two-tailed). The correlation between the post3dVA and post 1mVA was significant. The post 1mVA ranged from 0.05 to 2.20, with an average visual acuity of 0.94 ± 0.74 (P< 0.05, two-tailed). The correlation between post 1mVA and post3mVA was significant. Also, paired t-tests comparing preoperative and postoperative visual acuity revealed a significant correlation (P< 0.05, two-tailed). The post3mVA was 0-1.00 with an average visual acuity of 0.44 ± 0.41. The postoperative foveal thickness ranged from 176.00 to 514.00 μm, with an average thickness of 281.10 ± 113.12 μm. Emergency 25-G minimally invasive vitrectomy can improve visual acuity and decrease the reoperation rate for patients who have acquired post-cataract infectious endophthalmitis. There were significant correlations between age, disease onset to operation time, preoperative and postoperative visual acuity, and postoperative macular thickness.


Highly Narrow-Band Polarization-Sensitive Solar-Blind Photodetectors Based on β-Ga2O3 Single Crystals.
To suppress noise from full daylight background or environmental radiation, a spectrally selective solar-blind photodetector is widely required in many applications that need detection of light within a specific spectral range. Here, we present highly narrow-band solar-blind photodetectors by light polarization engineering of the anisotropic transitions in β-Ga2O3 single crystals. The polarized transmittance characteristics reveal that direct transitions from valance subbands to the conduction band minimum are tuned between 4.53 and 4.76 eV for the light polarized E// c and E// b. The polarization-dependent photoresponsivity verifies that the order of fundamental band-to-band transitions obeys well the selection rules in terms of the valence-band splitting in the β-Ga2O3 monoclinic crystal band structure. By combining an orthogonally aligned identical β-Ga2O3 (100) single crystal filter with a detector measured at a chopper frequency of 17 Hz, a highly narrow-band detection is produced with a peak responsivity of 0.23 A/W at 262 nm, an EQE of 110%, a bandwidth of 10 nm, a light rejection ratio over 800, and a response time of 0.86 ms. This provides a new paradigm for a narrow-band solar-blind photodetector with broad applications where background noise emission needs to be suppressed.


Rare anatomical variant: arterial circle in palm and at the base of the thumb.
In this article, we describe anomalous formation, distribution of superficial palmar arch and an arterial circle at the base of the thumb found during routine dissection classes in the right hand of a 45-year-old male cadaver. These variations are unique and provide significant information to surgeons dissecting the hand region.


Psoriasis, chronic tonsillitis, and biofilms: Tonsillar pathologic findings supporting a microbial hypothesis.
Group A Streptococcus has been identified as a possible etiologic agent in psoriasis in epidemiologic, immunologic, immunopathologic, medical, and surgical studies. Tonsillectomy has been shown to provide considerable relief to 75% of patients with plaque psoriasis. Even with the substantial evidence supporting group A Streptococcus as a causative pathogen in psoriasis, it is an elusive pathogen because it is not culturable, nor does it exhibit any positive serologic evidence of its presence. One possible reason for the negative cultures and negative serology findings with group A Streptococcus is the development of biofilms. We conducted a pathologic study to determine whether biofilms were present in the tonsillar tissues of 10 patients with psoriasis-6 men and 4 women, aged 25 to 64 years (mean: 48)-and in 10 age- and sex-matched controls with chronic tonsillitis who did not have psoriasis. We found that biofilms were present in every tonsillectomy specimen we examined, including those of the controls. Whereas psoriasis has been considered a "double hit" phenomenon, we believe that the development of skin lesions is likely attributable to the presence of the gene PSORS together with the biofilm in psoriasis patients rather than to the biofilm itself. Biofilms have been identified in both extra- and intracellular locations. We believe our findings add further evidence supporting a microbial pathogenesis of this disease.


Icariin protects rotenone-induced neurotoxicity through induction of SIRT3.
Sirtuin-3 (SIRT3) is a mitochondrial NAD + -dependent deacetylase that is essential in regulating mitochondrial proteins and maintaining cellular antioxidant properties. It has been reported that icariin (ICA) is neuroprotective over various neurotoxicant induced oxidative stress. This study aimed to determine whether ICA exerts neuroprotective effects on rotenone (ROT)-induced neurotoxicity through activation of SIRT3. Rats treated with ROT exhibited a marked loss of dopamine (DA) neurons and a decline in motor function, along with a decrease in protein expressions of SIRT3 and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) in the substantia nigra (SN). Administration of ICA significantly alleviated the loss of DA neurons, improved behavioral function, and concomitantly enhanced SIRT3 and PGC-1α expressions. The neuroprotective effect of ICA on ROT-induced cytotoxicity was further confirmed in the PC12 cell model, which showed significant improvement in the survival of ROT-treated cells with ICA pretreatment. The cytoprotective effect of ICA was abolished in ROT-treated cells by SIRT3 inhibitor 3-(1H-1,2,3-triazol-4-yl) pyridine (3-TYP), along with a resultant decrease in PGC-1α expression. In addition, knockdown of PGC-1α by siRNA suppressed ICA-mediated protective effects but did not affect SIRT3 expression, indicating the role of regulation of PGC-1α by SIRT3 in the protective action of ICA. Furthermore, we showed that ICA improved mitochondrial respiration, oxidative status, enhanced antioxidant enzyme SOD activity and GSH/GSSG ratio in cells treated with ROT. However, these protective effects of ICA on ROT-treated cells was markedly abolished by SIRT3 inhibitor 3-TYP. Our findings demonstrate that ICA exerts a neuroprotective role through upregulation of SIRT3.


Heteroprotein Complex Coacervate Based on β-Conglycinin and Lysozyme: Dynamic Protein Exchange, Thermodynamic Mechanism, and Lysozyme Activity.
Heteroprotein complex coacervate (HPCC) is a liquid-like protein concentrate produced by liquid-liquid phase separation. We revealed the protein dynamic exchange and thermodynamic mechanism of β-conglycinin/lysozyme coacervate, and clarified the effect of HPCC on protein structure and activity. β-conglycinin and lysozyme assembled into coacervate at pH 5.75-6.5 and assembled into amorphous precipitates at higher pH. As the pH dropped from 8 to 6, the number of binding sites of the complex decreased in half, and the desolvation degree corresponding to the entropy gain was greatly reduced, conducing to the formation of coacervates rather than precipitates. The coacervates achieved the unique dynamic exchange by exchanging proteins with the diluted phase, making the uniform distribution of proteins in coacervates. The lysozyme activity was completely retained in β-conglycinin/lysozyme coacervates. These results proved that β-conglycinin-based heteroprotein complex coacervate is a feasible method to encapsulate and enrich active proteins in a purely aqueous environment.


Underuse of controller medications among Medicaid-insured children with asthma.
National guidelines recommend daily use of controller medications for children with persistent asthma. Although studies suggest low rates of controller use, little is known about predictors of underuse among low-income children in whom asthma morbidity is greatest. To determine the frequency of underuse of controller medications among Medicaid-insured children in a variety of managed care arrangements, and to examine demographic factors and processes of asthma care associated with underuse. Cross-sectional telephone survey of parents of children and adolescents aged 2 to 16 years with asthma, insured by Medicaid, and enrolled in 1 of 5 managed care plans. The main outcome was parent-reported underuse of controllers among children with persistent asthma. Survey items included demographic factors and reports of specific processes of care. Current symptom level was determined by recall of the number of days with symptoms in the previous 14 and by the Physical Function Score of the American Academy of Pediatrics (AAP) Child Health Status Assessment for Asthma. Logistic regression was used to identify factors independently associated with underuse. The response rate was 66%, with 1648 children included in the analysis; 1083 were classified as having persistent asthma. Of these, 73% were underusers of controller therapy, with 49% reporting no controller use and 24% reporting less than daily use. A multivariate model that adjusted for age, managed health care organization, and AAP Physical Function Score found that black (odds ratio [OR], 1.7; 95% confidence interval [CI], 1.2-2.4) or Latino (OR, 2.2; 95% CI, 1.3-3.8) race were associated with underuse and that parental education beyond high school was protective (OR, 0.6; 95% CI, 0.4-0.8). Having a primary care physician (OR, 0.4; 95% CI, 0.2-0.8), written action plan (OR, 0.5; 95% CI, 0.4-0.7), or a follow-up visit (OR, 0.5; 95% CI, 0.4-0.8) and having seen an asthma specialist (OR, 0.5; 95% CI, 0.4-0.7) were associated with lower rates of underuse. Underuse of controller medications among Medicaid-insured children is widespread. Racial minorities and children whose parents are less educated are at higher risk for underuse. Patients who have received action plans or had follow-up visits or specialty consultations are less likely to be symptomatic underusers of controller medications.


Hyperglycemia in the Hospital Setting.
Nurses who understand contributing factors to insulin action and uncontrolled glucose and insulin action can assist in promoting optimal care. Common barriers to glucose control and current best practices in the acute care setting are reviewed.


Chemical modification studies of beef-heart mitochondrial b-c1 complex. Effect of modification by ethoxyformic anhydride.
The effect of the histidine-modifier ethoxyformic anhydride (EFA) on the enzymatic properties of the mitochondrial b-c1 complex (ubiquinol-cytochrome c reductase) has been investigated. Chemical modification by EFA inhibited to the same extent the reductase and the proton translocating activity of the complex. In particular EFA modification of the complex resulted in: strong inhibition of the antimycin-insensitive reduction of b cytochromes; inhibition of the antimycin-promoted oxidant-induced reduction of b cytochromes and inhibition of oxidation of pre-reduced b cytochromes. Analysis of the absorbance at 238 nm, indicative of N-(ethoxyformyl)histidine derivative, of the various polypeptide subunits separated by high-pressure liquid chromatography procedure, showed that EFA modified residues in core proteins and in the low-molecular-mass proteins. Both the inhibition of the redox and the protonmotive activity of the complex and the absorbance increase at 238 nm of the core protein fraction were readily reversed by hydroxylamine, indicating that modification of histidine residue(s) in core protein(s) is critical for the activity of the complex. This was supported by the finding that modification of the reductase with EFA prevented binding of fluorescein isothiocyanate to histidine residue(s) in core protein II. EFA modification of the reductase was without effect on the binding of N-(7-dimethylamino-4-methylcoumarinyl)maleimide to the various polypeptides of the complex except for the binding to the Fe-S protein which was greatly potentiated. Thus primary chemical modification of histidine residue(s) in core protein (II) appears to cause, in turn, a conformational change in the Rieske Fe-S protein.


Doppler sonography of deep cavernosal artery of the penis: variation of peak systolic velocity according to sampling location.
To determine if there are significant variations in the peak systolic velocity of cavernosal arteries according to the Doppler sampling location, Doppler sonography was performed in 32 patients with erectile dysfunction and 15 control patients. Doppler spectral waveforms were obtained at proximal and distal locations in cavernosal artery. The peak systolic velocity of the cavernosal artery was 39.0 +/- 11.2 cm/sec in proximal portion and 20.0 +/- 5.6 cm/sec in distal portion in patients with erectile dysfunction. In control patients, the peak systolic velocity was 39.8 +/- 8.0 cm/sec in proximal portion and 21.3 +/- 5.5 cm/sec in distal portion. The peak systolic velocity of the cavernosal artery varies significantly according to the sampling location in patients with erectile dysfunction as well as in control patients. Our study demonstrated that the sampling location needs to be standardized in performing Doppler sonography of the cavernosal arteries, and we propose the proximal cavernosal artery where it angles posteriorly as the standardized sampling location.


[Construct tissue-engineered bone by co-seeding marrow stromal cells and endothelial cells].
To identify the role of co-seeding marrow stromal cells (MSCs) and endothelial cells (ECs) onto biocomposite in constructing tissue-engineered bone for promoting osteogenesis and angiogenesis, we seeded rat marrow stromal cells (rMSCs) and human umbilical vein endothelial cells (hUVECs) onto poly (L-lactic acid)/beta-tricalcium phosphate (PLLA/beta-TCP) macroporous composite (the test group), and seeded rMSCs onto the same kind of composite (the control group). We implanted these biocomposites into the thighs of nude mice intramuscularly and sacrificed these mice at 1, 4, 8, 12, 16 weeks after implantation, respectively. Biocomposites were taken out and histomorphometry was performed. Image manipulation technology was used to calculate the percentages of new bone area and material area in the test group and control group. We found that the percentage of new bone area of test group increased faster than that of control group, the percentage of material of test group decreased faster than that of control group, and the growth of capillary network of test group was much better than that of control group. These results suggest that co-seeding MSCs and ECs onto scaffold for constructing tissue-engineered bone is beneficial to osteogenesis, to angiogenesis in the prosthesis, and to the degradation of scaffold, and it is of significance in the research of bone tissue engineering.


Choice and Utility of Pacing Maneuver in Establishing the Mechanism of Supraventricular Tachycardia: A Single Center Experience.
To evaluate the choice and utility of pacing maneuvers in the electrophysiology (EP) laboratory in establishing supraventricular tachycardia (SVT) mechanism. We retrospectively examined a cohort of 160 consecutive patients with SVT presenting for invasive EP evaluation to a single center with 8 electrophysiologists. We analyzed the utility of the two most commonly used pacing maneuvers: (1) ventricular entrainment (VE) and (2) His-refractory premature ventricular stimuli (HRPVC) during SVT. VE was performed in 96 patients: atrial tachycardia (AT) 12, atrioventricular nodal reentrant tachycardia (AVNRT) 66, and orthodromic reciprocating tachycardia (ORT) 18. During VE, AT patients were most likely to have ventriculo-atrial (VA) dissociation (AT 58%, AVNRT 18%, ORT 0%, P < 0.001) and had a tendency towards less SVT termination (AT 0%, AVNRT 9%, ORT 11%, P = 0.19). HRPVCs were delivered in 39 patients: AT 1, AVNRT 24, and ORT 14. Advancement of atrial signal with HRPVC was only observed in ORT (AT 0%, AVNRT 0%, ORT 79%, P < 0.001) and SVT termination was also mostly observed in ORT (AT 0%, AVNRT 4%, ORT 21%, P = 0.33). The overall diagnostic utility of VE was lowest in AT (AT 42%, AVNRT 71%, ORT 83%, P = 0.04), while HRPVC was rarely used in AT. Furthermore, the utilization of maneuvers varied extensively (0% to100%) among the 8 electrophysiologists. There is great variation in the utilization of pacing maneuvers and their utility in ascertaining the mechanism of SVT. Our results support the fact that discerning AT from AVNRT mechanism remains the most challenging task in SVT diagnosis.


[Successful operation for two cases of an aneurysmal bone cyst of the rib].
An aneurysmal bone cyst involving the rib is very rare. A 43-year-old man and 49-year-old woman complained of pain and swelling on the chest. X-ray and CT revealed a local expansion and honeycomb lesion of the right 9th rib. Surgical excision of the rib were performed to remove the tumor completely. The histopathological examination revealed that the lesion consisted of many cavities filled with blood and trabecullae containing osteoid tissue and giant cells, showing it to be an aneurysmal bone cyst. Because of the potential for the rapid growth and difficulty in differentiation between benign and malignant rib tumor, an excisional biopsy should be considered for the treatment of an aneurysmal bone cyst of the rib.


[Paleoamygdala: a comparative analysis of structural and functional organization in wAG/Rij and Wistar rats].
A comparative analysis of structural and functional organization of paleoamygdala was performed in 22 male WAG/Rij and Wistar rats using light microscopy (Nissl staining method and computer morphometric analysis), electron microscopy (using the criteria of the evaluation of the functional state of neurons) and the TUNEL method for apoptotic cell labeling. The results obtained suggest the involvement of the limbic brain structures in the pathogenesis of absence epilepsy. It was shown that the area occupied in the sections by amygdala was significantly greater in WAG/Rij rats (model of absence epilepsy). The assessment of ultrastructural characteristics of neurons in all the structures of paleoamygdala (dorsomedial, posterior medial and posterior cortical nuclei) has shown the signs of the reduction of their functional activity in WAG/Rij rats. In addition, WAG/Rij rats demonstrated the increased numbers of pyknomorphic neurons with the signs of apoptosis, as identified by the TUNEL method, which is indicative of the destructive processes.


Implicit and Explicit Beliefs About the Effectiveness of Psychotherapy vs. Medication: A Large-Scale Examination and Replication.
One exploratory study (N = 10,335) and one preregistered replication and extension study (N = 6648) evaluated implicit and explicit beliefs in the effectiveness of psychotherapy versus medication, and whether these beliefs vary as a function of demographics, mental health difficulties, and treatment experiences. Data were collected from a sample of visitors to a mental health research website who completed the Therapy vs. Medication Effectiveness Implicit Association Test (IAT). The IAT demonstrated evidence of convergent validity with two measures of explicit therapy versus medication effectiveness beliefs. Across both studies, individuals held greater implicit and explicit beliefs that therapy is more effective than medication, and individuals who were Black (versus all other races, excluding "other/unknown") and who had experienced past (versus current) mental health difficulties had stronger implicit and explicit beliefs in the effectiveness of therapy versus medication. More work is needed to understand how these differences in beliefs arise, as well as to evaluate the clinical utility of this novel measure.


Concomitant ipsilateral traumatic dislocation of the hip and knee following high-energy trauma: a case report.
Traumatic dislocation of the hip or knee can occur after high-energy trauma and is often associated with concomitant injuries and secondary complications. Concomitant traumatic dislocation of both hip and knee is rare. We describe a case of combined ipsilateral posterior hip dislocation with a posterior acetabular fracture and a complete open knee dislocation with disruption of the popliteal artery that resulted in amputation.


Skin sensitization in silico protocol.
The assessment of skin sensitization has evolved over the past few years to include in vitro assessments of key events along the adverse outcome pathway and opportunistically capitalize on the strengths of in silico methods to support a weight of evidence assessment without conducting a test in animals. While in silico methods vary greatly in their purpose and format; there is a need to standardize the underlying principles on which such models are developed and to make transparent the implications for the uncertainty in the overall assessment. In this contribution, the relationship between skin sensitization relevant effects, mechanisms, and endpoints are built into a hazard assessment framework. Based on the relevance of the mechanisms and effects as well as the strengths and limitations of the experimental systems used to identify them, rules and principles are defined for deriving skin sensitization in silico assessments. Further, the assignments of reliability and confidence scores that reflect the overall strength of the assessment are discussed. This skin sensitization protocol supports the implementation and acceptance of in silico approaches for the prediction of skin sensitization.


[Interleukin-17-mediated inflammation promotes nonalcoholic fatty liver disease in mice with regulation of M1-type macrophage polarization].
Objective: To study the mechanism of interleukin (IL)-17 in mice with non-alcoholic fatty liver disease for promoting M1-type macrophage polarization to exacerbate liver inflammation, and to provide references for the mechanism of NAFLD occurrence and development. Methods: A mouse model of NAFLD was constructed by high-fat diet. Mice were divided into control group, model group, IL-17 group, and anti IL-17 group. Histopathological changes of the liver were observed by HE staining. The serum levels of ALT and AST in peripheral blood of mice was detected by chemical colorimetry. Macrophages labeled with F4/80-PE, CD11C-FITC was designated as M1-type macrophages, those labeled with F4/80-PE, and CD206-APC was designated as M2-type macrophages. The proportion of M1 and M2 macrophages infiltrated into the liver tissues of mice were measured by flow cytometry. CD168 expression level of liver tissues was detected using immunohistochemistry. Protein and mRNA levels of the marker molecules (iNOS, TNF-alpha and IL-6) of M1 macrophages were detected using ELISA and RT-Q PCR. Western blot was used to detect the protein expression of JAK-STAT signal pathway and the expression level of MCP-1. Data were analyzed using one-way ANOVA and t-test. Results: High-fat diet NAFLD mice model was successfully constructed. IL-17 had increased the proportion of M1 macrophages in mice liver tissues and decreased the proportion of M2 macrophages (P < 0.05). The proportion of M1 and M2 macrophages in the liver tissues of normal mice was 7.9% ± 1.1% and 19.2% ± 1.8%. The proportion of M1 and M2 macrophages in the model group was 17.3% ± 2.5% and 15.0% ± 2.1. The proportion of M1 macrophages (33.8% ± 4.2%) in IL-17 group was higher than model group, while the proportion of M2 macrophages (7.8% + 1.0%) in IL-17 group was lower than model group. Protein and mRNA marker levels of M1 macrophage (iNOS, IL-12, TNFα and IL-6) in liver tissues were significantly higher than model group, control group, and anti-IL-17 group (P < 0.05). The expression levels of JAK1, STAT1, MCP-1, and CD168 in mice liver tissues of IL-17 group had increased (P < 0.05). The levels of aspartate and alanine aminotransferases in peripheral blood of mice in IL-17 group were significantly higher than other three groups (P < 0.05). Conclusion: IL-17 can promote M1-type macrophage polarization, and exacerbates the liver inflammatory response to accelerate the progression of NAFLD in mice.


Genital ulcer as a new clinical clue to PFAPA syndrome.
Vaginal ulcers can be associated with a number of different diseases. We describe two girls who presented genital ulcers as a persistent symptom of PFAPA (periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis) syndrome. The possibility of considering this clinical manifestation as a clue for the diagnosis of PFAPA is discussed.


Futile medication use in terminally ill cancer patients.
Cancer patients usually take many medications. The proportion of patients with advanced cancer who are taking futile drugs is unknown. We retrospectively reviewed the charts of all consecutive ambulatory patients with advanced cancer and who were receiving supportive care exclusively at palliative care clinics, Princess Margaret Hospital, to gather information on futile medications used by them. Futile medications were defined as unnecessary (when no short-term benefit to patients with respect to survival, quality of life, or symptom control was anticipated) or duplicate (two or more drugs from the same pharmacological class). Summary statistics were used to describe the results. From November 2005 to July 2006, 82 (22%) of 372 patients were taking at least one futile medication before consultation; after initial consultation, this proportion dropped to 20% (78): 70 patients were taking unnecessary medications, while eight were on duplicate medications. The most frequent unnecessary medications used by patients were statins (56%). The most common duplicate medication involved the use of two different benzodiazepines (seven patients). About one fifth of cancer outpatients at the end of life take futile medications, most commonly statins. Prospective and population-based studies are warranted to further evaluate the magnitude and consequences of futile medication use in oncology.


The molecular basis of copper homeostasis copper-related disorders.
Copper is an essential trace element that can be extremely toxic in excess due to the pro-oxidant activity of copper ions. Inherited disorders of copper transport, Menkes disease (copper deficiency), and Wilson disease (copper toxicosis) are caused by mutations of two closely related Cu transporting-ATPases, and demonstrate the essentiality and potential toxicity of copper. Other copper toxicosis conditions in humans and animals have been described, but are not well understood at a molecular level. Copper homeostatic mechanisms are being discovered. One such mechanism is copper-induced trafficking of the Cu-ATPases, which allows cells to provide copper to secreted cupro-proteins but also to efflux excess copper. Oxidative damage induced by copper may be involved in the pathogenesis of neurodegenerative conditions such as Alzheimer's disease, familial amyotrophic lateral sclerosis, and prion diseases.


Accumulation of novel glycolipids and ornithine lipids in Mesorhizobium loti under phosphate deprivation.
Glycolipids are found mainly in photosynthetic organisms (plants, algae, and cyanobacteria), Gram-positive bacteria, and a few other bacterial phyla. They serve as membrane lipids and play a role under phosphate deprivation as surrogates for phospholipids. Mesorhizobium loti accumulates different di- and triglycosyl diacylglycerols, synthesized by the processive glycosyltransferase Pgt-Ml, and two so far unknown glycolipids, which were identified in this study by mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy as O-methyl-digalactosyl diacylglycerol (Me-DGD) and glucuronosyl diacylglycerol (GlcAD). Me-DGD is a novel glycolipid, whose synthesis depends on Pgt-Ml activity and the involvement of an unknown methyltransferase, while GlcAD is formed by a novel glycosyltransferase encoded by the open reading frame (ORF) mlr2668, using UDP-glucuronic acid as a sugar donor. Deletion mutants lacking GlcAD are not impaired in growth. Our data suggest that the different glycolipids in Mesorhizobium can mutually replace each other. This may be an adaptation mechanism to enhance the competitiveness in natural environments. A further nonphospholipid in Mesorhizobium was identified as a hydroxylated form of an ornithine lipid with the additional hydroxy group linked to the amide-bound fatty acid, introduced by the hydroxylase OlsD. The presence of this lipid has not been reported for rhizobia yet. The hydroxy group is placed on the C-2 position of the acyl chain as determined by NMR spectroscopy. Furthermore, the isolated ornithine lipids contained up to 80 to 90% d-configured ornithine, a stereoform so far undescribed in bacteria.


Inter-dye distance distributions studied by a combination of single-molecule FRET-filtered lifetime measurements and a weighted accessible volume (wAV) algorithm.
Förster resonance energy transfer (FRET) is an important tool for studying the structural and dynamical properties of biomolecules. The fact that both the internal dynamics of the biomolecule and the movements of the biomolecule-attached dyes can occur on similar timescales of nanoseconds is an inherent problem in FRET studies. By performing single-molecule FRET-filtered lifetime measurements, we are able to characterize the amplitude of the motions of fluorescent probes attached to double-stranded DNA standards by means of flexible linkers. With respect to previously proposed experimental approaches, we improved the precision and the accuracy of the inter-dye distance distribution parameters by filtering out the donor-only population with pulsed interleaved excitation. A coarse-grained model is employed to reproduce the experimentally determined inter-dye distance distributions. This approach can easily be extended to intrinsically flexible proteins allowing, under certain conditions, to decouple the macromolecule amplitude of motions from the contribution of the dye linkers.


Optical Limiting and Theoretical Modelling of Layered Transition Metal Dichalcogenide Nanosheets.
Nonlinear optical property of transition metal dichalcogenide (TMDC) nanosheet dispersions, including MoS2, MoSe2, WS2, and WSe2, was performed by using Z-scan technique with ns pulsed laser at 1064 nm and 532 nm. The results demonstrate that the TMDC dispersions exhibit significant optical limiting response at 1064 nm due to nonlinear scattering, in contrast to the combined effect of both saturable absorption and nonlinear scattering at 532 nm. Selenium compounds show better optical limiting performance than that of the sulfides in the near infrared. A liquid dispersion system based theoretical modelling is proposed to estimate the number density of the nanosheet dispersions, the relationship between incident laser fluence and the size of the laser generated micro-bubbles, and hence the Mie scattering-induced broadband optical limiting behavior in the TMDC dispersions.


[Translation into Spanish and validation of the Snaith-Hamilton Pleasure Scale (SHAPS) for anhedonia].
The inability to experience pleasure, anhedonia, is recognized as al hallmark symptom of depression. A 14-item, self-report scale developed for the assessment of hedonic capacity: the Snaith-Hamilton Pleasure Scale (SHAPS) has proved to be a reliable and valid psychometric instrument. Because there are no versions of the scale in other languages, our objective in this study was to translate the instrument into spanish and to determine if the new version maintained the validity and reliability of its original english version. The scale was translated into spanish and after reaching final consensus applied to a group of depressed patients participating in a pharmacological trial. The Hamilton Depression Rating Scale (HDRS) was also applied for comparative purposes. Our results demonstrate that the SHAPS in its spanish version maintains the validity and reliability level of the original english version. A moderate internal consistency was determined by Cronbach alpha value of 0.77. our results demonstrate the the spanish version of the SHAPS has validity and reliability similar to its original version, and thus it represents a good alternative to evaluate anhedonia in spanish-speaking populations.


Generation and dose distribution measurement of flash x-ray in KALI-5000 system.
Flash x-ray generation studies have been carried out in KALI-5000 Pulse power system. The intense relativistic electron beam has been bombarded on a tantalum target at anode to produce flash x-ray via bremsstrahlung conversion. The typical electron beam parameter was 360 kV, 18 kA, and 100 ns, with a few hundreds of A/cm(2) current density. The x-ray dose has been measured with calcium sulfate:dysposium (CaSO(4):Dy) thermoluminescent dosimeter and the axial dose distribution has been characterized. It has been observed that the on axis dose falls of with distance approximately 1/x(n), where n varies from 1.8 to 1.85. A maximum on axis dose of 46 mrad has been measured at 1 m distance from the source. A plastic scintillator with optical fiber coupled to a photomultiplier tube has been developed to measure the x-ray pulse width. The typical x-ray pulse width varied from 50 to 80 ns.


Efficacy and safety of stepwise introduction of insulin lispro mix 50 in Japanese patients with type 2 diabetes inadequately controlled by oral therapy.
The objective of this study was to evaluate the efficacy and safety of stepwise introduction of insulin lispro mix 50 (LM50) from once to 3 times daily in Japanese patients with type 2 diabetes mellitus inadequately controlled by oral therapy. This was a multicenter, open-label, non-randomized trial consisting of three 16-week periods (48 weeks total); all patients were given once-daily injections of LM50 in Period 1. The regimen was intensified to twice daily in Period 2, and 3 times daily in Period 3 if HbA1c was ≥ 6.9% before the start of the period. A total of 135 patients were enrolled, and 116 patients completed the study. Main baseline characteristics of enrolled patients were a mean age of 60.3 years, mean diabetes duration of 11.4 years, mean BMI of 25.2 kg/m(2), and mean HbA1c of 8.71%. The percentages of patients who achieved HbA1c levels <6.9% and <7.4% at endpoint were 18.5% (25/135 patients) and 52.6% (71/135 patients), respectively. Mean HbA1c decreased significantly from 8.70% to 7.44% (p<0.001). The incidence of hypoglycemic episodes over the treatment periods was 65.9% (89/135 patients); severe hypoglycemia occurred in 2.2% (3/135 patients). There were no other clinically significant safety issues related to the study drug. Stepwise introduction of LM50 from once to 3 times daily can be a safe, effective, and simple therapy for Japanese patients with type 2 diabetes mellitus inadequately controlled by oral therapy.


Aging and place--neighborhoods and health in a world growing older.
The articles in this special issue make it clear that there are interesting and policy-relevant research to identify place-based strategies to improve health and reduce health disparities among older adults. The articles also reveal important areas of future research and policy innovation that are needed related to place and aging.


RESTRICTION FRAGMENT ANALYSIS OF PINE PHYLOGENY.
We used restriction fragment analysis of chloroplast, nuclear, and mitochondrial DNA to study phylogeny in the genus Pinus. Total genomic DNA of 18 to 19 pine species that spanned 14 of the 15 subsections in the genus was cut with 8 restriction enzymes, blotted, and then probed with up to 17 cloned DNA fragments-which were mostly from the chloroplast genome of Douglas-fir (Pseudotsuga menziesii [Mirb.] Franco). A total of 116 shared characters, the majority representing single point mutations, were subjected to Wagner and Dollo parsimony analyses, coupled with bootstrapping and construction of consensus trees. The hard (subgenus Pinus) and soft pines (subgenus Strobus) were distinct. The soft pines in section Parrya, represented by P. longaeva, edulis, monophylla, and gerardiana, were the group closest to the hypothesized root of the genus. They were also more diverse and more closely related to the hard pines than were their descendents in section Strobus, represented by P. koraiensis, albicaulis, griffithii, and lambertiana, all of which were remarkably similar. Except for a strong clade involving P. canariensis and pinea (section Ternatae), the hard pines were weakly differentiated. The high similarity within the most speciose groups of pines (sections Strobus and Pinus) suggests that the bulk of the genus radiated relatively recently. In contrast to a recent classification, P. leiophylla was not associated with section Ternatae; instead, it appears to belong in section Pinus, and showed a high similarity to P. taeda of subsection Australes. Subsection Oocarpae, represented by P. oocarpa and radiata, appears to be a natural group, and is related to subsection Contortae, represented by P. contorta. More extensive restriction fragment studies will yield many new insights into evolution in the genus. Other methods, however, such as DNA sequencing or fine structure analysis of restriction site mutations, are likely to be necessary for rooting pine phylogenies with respect to other coniferous genera, and for estimating divergence times.


Expressed attitudes of adolescents toward marriage and family life.
In the U.S., modifications in family structure and in attitudes concerning marriage and family life have been numerous. Areas such as sexual behavior and alternative living arrangements have become highly varied and nontraditional compared to past generations. This study examined the attitudes of adolescents toward aspects of marriage and family life. The majority of adolescents expressed negative attitudes toward divorce and viewed marriage as a lifelong commitment. While only about a third of the adolescents expressed positive attitudes toward premarital sex, a majority indicated they would engage in sexual intercourse before marriage, or already have. Interestingly, about half of the adolescents held positive attitudes toward cohabitation. Lastly, the adolescents demonstrated a growing acceptance of premarital counseling and psychoeducational interventions regarding marriage and family life.


The Nearctic-Caribbean species Leptotrachelus dorsalis (Fabricius, 1801): Larval descriptions with a diagnosis of immature Ctenodactylini and natural history notes on the genus and tribe (Coleoptera, Carabidae).
Adults and larvae of Leptotrachelus dorsalis (Fabricius), the Sugarcane Savior Beetle, live in association with grasses, the larvae in the appressed leaf axils. Both adult and larval Leptotrachelus dorsalis eat larvae of the Sugarcane Borer, Diatraea saccharalis (Fabricius), and perhaps other insects living in the confines of the leaf sheaths of that and other grass-like species. The geographic range of Leptotrachelus dorsalis extends from Kansas in the west to the Atlantic seaboard, north as far as Ontario, Canada and south to Cuba; it is an eastern species of North America and the Caribbean. Larval character attributes that are shared with a related ctenodactyline, Askalaphium depressum (Bates), provide a preliminary basis for characterization of the immatures of tribe Ctenodactylini.


Mediastinal neurothekeoma: a rare tumor.
Neurothekeoma, also known as nerve sheath myxoma, is a benign nerve sheath tumor that usually arises in the cutaneous nerves of the head, neck, or upper extremities. Extracutaneous placement is very rare. Mediastinal neurothekeoma has not previously been reported in the English literature. A 30-year-old woman was admitted to our clinic with back pain. A smooth-edged mass found in her paravertebral region, and a neurogenic tumor was suspected. The tumor was completely excised. Final pathology revealed it to be a mediastinal neurothekeoma.


A spinal pathway between synergists can modulate activity in human elbow flexor muscles.
Electrical stimulation of the brachioradialis branch of the radial nerve has been shown to inhibit the discharge of voluntarily activated motor units in biceps brachii during weak contractions with the elbow flexor muscles. The purpose of the present study was to characterise the inhibitory reflex by comparing its strength in the short and long heads of the biceps brachii and examining the influence of forearm position on the strength of the reflex. Spike-triggered stimulation was used to assess the influence of radial nerve stimulation on the discharge of single motor units in the biceps brachii of 15 subjects. Stimulation of the radial nerve prolonged the interspike interval (P < 0.001) of motor units in the long (n = 31, 4.8 +/- 5.6 ms) and short heads (n = 26, 8.1 +/- 12.3 ms) of biceps brachii with no difference between the two heads (P = 0.11). The strength of inhibition varied with forearm position for motor units in both heads (n = 18, P < 0.05). The amount of inhibition was greatest in pronation (7.9 +/- 8.9 ms), intermediate in neutral (5.8 +/- 7.1 ms), and least in supination (2.8 +/- 3.4 ms). These findings indicate that the inhibition evoked by afferent feedback from brachioradialis to low-threshold motor units (mean force 3-5% MVC) in biceps brachii varied with forearm posture yet was similar for the two heads of biceps brachii. This reflex pathway provides a mechanism to adjust the activation of biceps brachii with changes in forearm position, and represents a spinal basis for a muscle synergy in humans.


Reactive oxygen species induce expression of vascular endothelial growth factor in chondrocytes and human articular cartilage explants.
Vascular endothelial growth factor (VEGF) promotes cartilage-degrading pathways, and there is evidence for the involvement of reactive oxygen species (ROS) in cartilage degeneration. However, a relationship between ROS and VEGF has not been reported. Here, we investigate whether the expression of VEGF is modulated by ROS. Aspirates of synovial fluid from patients with osteoarthritis (OA) were examined for intra-articular VEGF using ELISA. Immortalized C28/I2 chondrocytes and human knee cartilage explants were exposed to phorbol myristate acetate (PMA; 0-20 microg/ml), which is a ROS inducer, or 3-morpholino-sydnonimine hydrochloride (SIN-1; 0-20 microM), which is a ROS donor. The levels of VEGF protein and nitric oxide (NO) production were determined in the medium supernatant, using ELISA and Griess reagent, respectively. Gene expression of VEGF-121 and VEGF-165 was determined by splice variant RT-PCR. Expression of VEGF and VEGF receptors (VEGFR-1 and VEGFR-2) was quantified by real-time RT-PCR. Synovial fluid from OA patients revealed markedly elevated levels of VEGF. Common RT-PCR revealed that the splice variants were present in both immortalized chondrocytes and cartilage discs. In immortalized chondrocytes, stimulation with PMA or SIN-1 caused increases in the levels of VEGF, VEGFR-1 and VEGFR-2 mRNA expression. Cartilage explants produced similar results, but VEGFR-1 was only detectable after stimulation with SIN-1. Stimulation with PMA or SIN-1 resulted in a dose-dependent upregulation of the VEGF protein (as determined using ELISA) and an increase in the level of NO in the medium. Our findings indicate ROS-mediated induction of VEGF and VEGF receptors in chondrocytes and cartilage explants. These results demonstrate a relationship between ROS and VEGF as multiplex mediators in articular cartilage degeneration.


Characteristics and onset of presentation of pediatric stiff skin syndrome: A retrospective cohort study of 11 patients in a tertiary care center.
Stiff skin syndrome (SSS) is a rare disorder characterized by "rock hard" indurated skin affecting different body parts. The localized variant poses a diagnostic challenge, as it is frequently mistaken for other inflammatory connective tissue disorders. The aim of this study is to provide insightful clinical, radiologic and diagnostic data that might prove useful for the evaluation, management and treatment of pediatric patients with segmental SS. This single-center cohort study included patients ≤18 years diagnosed with localized SSS from 1988 to 2021 in a quaternary pediatric healthcare center in Toronto, Canada. Data included demographics, clinical, histopathologic and radiologic features, treatments, and clinical course. Data were summarized with descriptive statistics (mean, standard deviation, medians, interquartile ranges [IQRs]) and frequencies. A total of 11 patients were included. The sclerotic changes were measured clinically and radiologically, by a total of 16 imaging studies: 13 magnetic resonance imaging (MRI) and 3 ultrasound. MRI readings showed abnormal high signal intensity of the affected tissue correlating with the anatomical site of involvement in all cases, specifically, in the shoulder/pelvic girdle with limb extension. Shear wave ultrasound elastography (SWE) demonstrated higher values within the dermis compared to the control site. The presence of segmental sclerotic changes that affects the pelvic/shoulder girdle with extension to the extremities, in the absence of inflammation on biopsy and abnormal signaling intensity on imaging is suggestive of SSS. Skin SWE is a feasible, noninvasive, and objective instrument to evaluate and monitor sclerotic changes overtime, it could be potentially extrapolated to other pediatric skin sclerotic conditions.


Localization of the site of oxygen radical generation inside the complex I of heart and nonsynaptic brain mammalian mitochondria.
Mitochondrial production of oxygen radicals seems to be involved in many diseases and aging. Recent studies clearly showed that a substantial part of the free radical generation of rodent mitochondria comes from complex I. It is thus important to further localize the free radical generator site within this respiratory complex. In this study, superoxide production by heart and nonsynaptic brain submitochondrial particles from up to seven mammalian species, showing different longevities, were studied under different conditions. The results, taking together, show that rotenone stimulates NADH-supported superoxide generation, confirming that complex I is a source of oxygen radicals in mammals, in general. The rotenone-stimulated NADH-supported superoxide production of the heart and nonsynaptic brain mammalian submitochondrial particles was inhibited both by p-chloromercuribenzoate and by ethoxyformic anhydride. These results localize the complex I oxygen radical generator between the ferricyanide and the ubiquinone reduction site, making iron-sulfur centers possible candidates, although unstable semiquinones can not be discarded. The results also indicate that the previously described inverse correlation between rates of mitochondrial oxygen radical generation and mammalian longevity operates through mechanisms dependent on the presence of intact functional mitochondria.


Low-dose right unilateral electroconvulsive therapy (ECT): effectiveness of the first treatment.
Electroconvulsive therapy (ECT) is a widely used, highly effective antidepressant treatment. Except for the most severely ill patients, right unilateral (RUL) electrode placement is the most frequent initial treatment choice. In current practice, RUL ECT is administered at several multiples of seizure threshold (ST) based on reports that lower stimulus intensity results in lower response/remission rates. Many patients, as part of an initial dose titration to determine ST, will receive a single treatment with low-dose RUL ECT and subsequent treatments with a stimulus at a multiple of ST. To assess response to the first ECT. A retrospective analysis of charts from clinical practice at Mount Sinai Medical Center was performed. A single treatment with low-dose (presumably near ST) RUL ECT had a significant and immediate antidepressant effect in our sample of patients with major depression. We determined that this response is similar to that of patients receiving a single initial treatment with high-dose RUL ECT (at a multiple of ST). These data suggest, contrary to commonly held belief, that RUL ECT may be effective at a low stimulus dose. This argues against restimulating at 6 times ST in the initial session, based on the belief that the near-threshold seizure has no antidepressant efficacy. Our findings suggest a need for further investigation of cases in which low-dose RUL ECT may be an effective antidepressant treatment. Further prospective studies, including larger numbers of patients who receive randomized treatment with low- or high-dose RUL with longer follow-up, are indicated.


Successful treatment of familial Mediterranean fever with Anakinra and outcome after renal transplantation.
Familial Mediterranean fever (FMF) is an autosomal recessive disease characterized by recurrent episodes of fever and inflammation. The most severe complication of FMF is the development of AA amyloidosis, which can be life threatening. The only current effective treatment for FMF is colchicine. Regular prophylactic treatment with colchicine at a dose of 1-2 mg daily prevents or substantially reduces the clinical manifestations of FMF in at least 90% of cases. However, approximately 10% of patients are reported to be resistant or non-responsive to colchicine and in these cases there is no consensus as to which second line agents should be used. We describe the first case, to our knowledge, of a patient with FMF and end-stage renal failure due to AA amyloidosis, successfully treated with IL-1 receptor blockade. Our data suggest that the IL-1 receptor antagonist Anakinra (Kineret; r-metHuIL-1 ra) may represent a safe and effective therapy for the treatment of colchicine-resistant FMF, in patients requiring renal replacement therapy, with dialysis or transplantation.


Optimal protective hypothermia in arrested mammalian hearts.
Many therapeutic hypothermia recommendations have been reported, but the information supporting them is sparse, and reveals a need for the data of target therapeutic hypothermia (TTH) from well-controlled experiments. The core temperature ≤35°C is considered as hypothermia, and 29°C is a cooling injury threshold in pig heart in vivo. Thus, an optimal protective hypothermia (OPH) should be in the range 29-35°C. This study was conducted with a pig cardiopulmonary bypass preparation to decrease the core temperature to 29-35°C range at 20 minutes before and 60 minutes during heart arrest. The left ventricular (LV) developed pressure, maximum of the first derivative of LV (dP/dtmax), cardiac power, heart rate, cardiac output, and myocardial velocity (Vmax) were recorded continuously via an LV pressure catheter and an aortic flow probe. At 20 minutes of off-pump during reperfusion after 60 minutes arrest, 17 hypothermic hearts showed that the recovery of Vmax and dP/dtmax established sigmoid curves that consisted of two plateaus: a good recovery plateau at 29-30.5°C, the function recovered to baseline level (BL) (Vmax=118.4%±3.9% of BL, LV dP/dtmax=120.7%±3.1% of BL, n=6); another poor recovery plateau at 34-35°C (Vmax=60.2%±2.8% of BL, LV dP/dtmax=28.0%±5.9% of BL, p<0.05, n=6; ), which are similar to the four normothermia arrest (37°C) hearts (Vmax=55.9%±4.8% of BL, LV dP/dtmax=24.5%±2.1% of BL, n=4). The 32-32.5°C arrest hearts showed moderate recovery (n=5). A point of inflection (around 30.5-31°C) existed at the edge of a good recovery plateau followed by a steep slope. The point presented an OPH that should be the TTH. The results are concordant with data in the mammalian hearts, suggesting that the TTH should be initiated to cool core temperature at 31°C.


Measles Transmission in a Fully Vaccinated Closed Cohort: Data From a Nosocomial Clustered Cases in a Teenage Psychiatric Unit.
We described nosocomially clustered cases of measles secondary to a nonvaccinated index case occurring in a teenage psychiatric unit despite optimum vaccine coverage. Surveillance of this fully vaccinated closed cohort showed a 7% attack rate. Vaccination limited the risk of complicated measles and the onset of a large outbreak.


Treatment of fungal infections with flucytosine.
Treatment with flucytosine of 20 patients with fungal infections gave favorable results in four patients with crytococcal infections, two of four patients with disseminated candidiasis, eight of ten patients with urinary tract infections due to Candida albicans and Torulopsis glabrata, and tow of three patients with miscellaneous infections due to Calbicans. Two patients with crytococcal meningitis and altered host resistance and one patient with an aorto femoral graft infection due to C albicans were treated with flucytosine and smphotericin B. The infection was eradicated in one of the patients with meningitis, and cultures from an infected arterial graft became negative. Adverse side effects of flucytosine included mild leukopenia and thrombocytopenia, a transient increase in alkaline phosphatase and glutamic oxaloacetic transaminase, and nausea and diarrhea.


With Some Help From My Network: Supplementing eHealth Literacy With Social Ties.
eHealth literacy is defined as the ability to seek, find, understand, and appraise health information from electronic sources and apply knowledge gained to addressing or solving a health problem. Previous research has shown high reliance on both online and face-to-face interpersonal sources when sharing and receiving health information. In this paper, we examine these interpersonal sources and their interplay with respondents' eHealth literacy and perceived health outcomes. Specifically, we look at how the relationship between eHealth literacy and health outcomes is moderated by (1) finding help while performing online activities, (2) finding others with similar health concerns online, and (3) the importance of finding others with similar health concerns for people from ethnic minorities, specifically Palestinian citizens of Israel versus Israeli Jews. We used a nationally representative random-digit dial telephone household survey of an Israeli adult population (age ≥21 years, N=819). The collected data were analyzed using two regression models. The first examined how the correlation between eHealth literacy and perceived outcomes was moderated by the availability of help. The second examined how the correlation between eHealth literacy and perceived outcomes was moderated by finding others with similar health concerns and by ethnicity. Respondents with low eHealth literacy who were able to recruit help when performing online activities demonstrated higher perceived health outcomes compared to similar respondents who did not find help. Respondents with low eHealth literacy, who were able to find others with similar health concerns (online), demonstrated higher perceived health outcomes when compared to similar respondents who did not find others with similar health concerns. Finally, finding similar others online was more helpful in enhancing health outcomes for ethnic minorities; Palestinian citizens of Israel gained more health benefits by finding similar others compared to Israeli Jews. Although the availability of help and the notion of ethnicity have been discussed extensively within the context of social capital and health, our findings offer initial evidence for the relevancy of these concepts when studying individuals' eHealth literacy. Specifically, our findings enable a better understanding of the role of social ties and ethnicity in moderating the interplay between eHealth literacy and perceived health outcomes. Given the increased importance of eHealth information, our findings enhance understanding of how social ties can potentially compensate for low eHealth literacy.


Resolution enhancement in coherent x-ray diffraction imaging by overcoming instrumental noise.
We report that reference objects, strong scatterers neighboring weak phase objects, enhance the phase retrieval and spatial resolution in coherent x-ray diffraction imaging (CDI). A CDI experiment with Au nano-particles exhibited that the reference objects amplified the signal-to-noise ratio in the diffraction intensity at large diffraction angles, which significantly enhanced the image resolution. The interference between the diffracted x-ray from reference objects and a specimen also improved the retrieval of the phase of the diffraction signal. The enhancement was applied to image NiO nano-particles and a mitochondrion and confirmed in a simulation with a bacteria phantom. We expect that the proposed method will be of great help in imaging weakly scattering soft matters using coherent x-ray sources including x-ray free electron lasers.


Association Between Nutritional Status, Inflammatory Condition, and Prognostic Indexes with Postoperative Complications and Clinical Outcome of Patients with Gastrointestinal Neoplasia.
The aim of this study is to describe and relate nutritional and inflammatory status and prognostic indexes with postoperative complications and clinical outcome of patients with gastrointestinal malignancies. Twenty-nine patients were evaluated; nutritional assessment was carried out by subjective and objective parameters; albumin, pre-albumin, C-reactive protein (CRP), and alpha-1-acid glycoprotein (AGP) were determined. To assess prognosis, the Glasgow scale, the Prognostic Inflammatory Nutritional Index (PINI), and CRP/albumin ratio were used; the clinical outcomes considered were hospital discharge and death. A high Subjective Global Assessment (SGA) score was associated with the occurrence of postoperative complications: 73% of the patients with postoperative complications had the highest SGA score, but only 6% of those without postoperative complications had the highest SGA score (P < 0.001). Greater occurrence of death was observed in patients with a high SGA score, low serum albumin, increased CRP, PINI > 1, and Glasgow score 2. There was a positive correlation between weight loss percentage with serum CRP levels (P = 0.002), CRP/albumin (P = 0.002), PINI (P = 0.002), and Glasgow score (P = 0.000). This study provides evidence that the assessment of the nutritional status and the use of prognostic indexes are good tools for predicting postoperative complications and clinical outcome in patients with gastrointestinal neoplasia.


Feedback is the best way to see.
A 60-year-old man with past history of acute mild pancreatitis (AP) in 1997 and 2005, recently with repeated attacks of AP 5 times in last 2 years. Repeated endoscopic ultrasonography (EUS) showed 20 mm cyst in pancreatic body with 5 mm nodule, main pancreatic duct (MPD) 4-6 mm, fine-needle aspiration malignant cell negative, mucin positive. Computed tomography and magnetic resonance imaging of branch duct intraductal papillary mucosal neoplasms with 10 mm branch duct. From 2011 to 2013, the cyst was without progression in size or character. Due to clinical course of repeated AP, endoscopic retrograde cholangiopancreatography was recommended. It revealed dilated MPD 5-7 mm and 15 mm × 13 mm cyst in pancreatic body. Distal pancreatectomy was indicated because of clinical course and "worrisome EUS features" - MPD size and intramural nodule. In terms of having feedback, endosonographer use to examine every resected specimen of pancreas in our hospital just after surgery. The resected body with "sand glass" appearance of the cyst of size 3 cm was totally different from what we saw previously. We rewinded the previous EUS documentation and made a new evaluation. EUS is unique method for pancreatic tumors, but only in combination with real image of specimen makes endosonographer to bow up.


Stimulation of neutrophils with a chemoattractant activates several novel protein kinases that can catalyze the phosphorylation of peptides derived from the 47-kDa protein component of the phagocyte oxidase and myristoylated alanine-rich C kinase substrate.
Novel protein kinases that may participate in the signal transduction pathways of neutrophils were sought by a procedure based on the ability of these enzymes to undergo renaturation and catalyze the phosphorylation of a peptide substrate fixed in a gel. We report that neutrophils contain four uncharacterized protein kinases with molecular masses of about 69, 63, 49, and 40 kDa, which are rapidly activated upon stimulation of these cells with the chemoattractant fMet-Leu-Phe. These kinases can catalyze the phosphorylation of a peptide that corresponds to residues 297-331 of the 47-kDa subunit of the NADPH oxidase system (p47-phox). A peptide that corresponds to residues 153-178 of the human myristolyated alanine-rich C kinase substrate (MARCKS) protein was also a substrate for the 69- and 63-kDa kinases. The time course for the activation of these enzymes was similar to the phosphorylation of p47-phox and MARCKS in intact neutrophils. In contrast, stimulation of these cells with 4 beta-phorbol 12-myristate 13-acetate, the calcium ionophore A23187, or the combination of these agonists did not activate these enzymes. Activation of the 63- and 40-kDa protein kinases was blocked by pertussis toxin, calyculin A, and staurosporine. Several other unidentified protein kinases were also active with these peptides but did not exhibit enhanced activity after cell stimulation with this method.


Comparative morphometric study of the australopithecine vertebral series Stw-H8/H41.
Lower spinal structure correlates well with positional behavior among mammals. Nonetheless, the functional morphology of the axial post-crania of australopithecines has received less attention than their appendicular skeletons. This paper presents a detailed description and comparative morphometric analysis of the australopithecine thoracolumbar vertebral series Stw-H8/H41, and examines spinal mechanics in early hominids. Stw-H8/H41 is an important specimen, as the australopithecine vertebral sample is small, and vertebral series are more useful than isolated elements for the interpretation of spinal function. Results of the study support the interpretation that australopithecine species are highly sexually dimorphic. The study also reveals a considerable amount of morphometric variation other than size among australopithecine vertebrae, though the sample is too small and incomplete to ascertain whether this indicates significant interspecific differences in spinal function. Most importantly, structural and metric observations confirm that the morphology of the lower spine in australopithecines has no modern analogue in its entirety. Aspects of zygapophyseal structure, numerical composition of the lumbar region, and centrum wedging suggest that the australopithecine vertebral column was adapted to human-like intrinsic lumbar lordosis and stable balance of the trunk over the pelvis in sustained bipedal locomotion. However, relative centrum size in australopithecines indicates that either they had a different mechanism for channeling vertical forces through the vertebral column than humans, or differed behaviorally from humans in ways that produced smaller increments of compression across their centra. These findings have important implications for hypotheses of australopithecine positional behavior, and demonstrate that larger samples and more complete vertebral series are needed to improve our understanding of australopithecine spinal function.


Reversal of natural killing susceptibility in target cells expressing transfected class I HLA genes.
A number of studies have suggested that resistance of target cells to natural killing (NK) may be correlated with their level of expression of major histocompatibility complex (MHC) class I antigens. To examine this hypothesis directly, a NK-sensitive class I-deficient human B-cell line was transfected with MHC class I genes. The expression of transfected HLA, but not H-2, class I gene products resulted in loss of susceptibility to human NK-mediated conjugation and cytolysis. Furthermore, this protection did not extend to cytotoxicity mediated by interleukin 2-stimulated human NK effector cells.


Association of Diabetic Neuropathy with Duration of Type 2 Diabetes and Glycemic Control.
Diabetes mellitus is associated with severe microvascular and macrovascular complications with major implications for public health. Diabetic neuropathy is a very problematic complication of diabetes mellitus. It is associated with severe morbidity, mortality, and a huge economic burden. The present study was designed with two aims: 1) to analyze the association of diabetic neuropathy with the glycemic index (levels of fasting blood glucose, random blood glucose, and Hb1Ac) in patients with Type 2 diabetes, and 2) to analyze the association of diabetic neuropathy with time passed since the diagnosis of diabetes. This case-control study was undertaken between June 2013 and February 2015 in the Armed Forces Institute of Rehabilitation Medicine (AFIRM), Rawalpindi, Pakistan. Type 2 diabetics with an age range of 30-60 years were recruited from outpatient departments of AFIRM, Rawalpindi. Data were collected and recorded on a form with four sections recording the following: 1) demographics of patients and number of years passed since diagnosis of diabetes; 2) clinical examination for touch, pressure, power, pain, vibration, and ankle reflex; 3) nerve conduction studies for motor components of the common peroneal nerve and tibial nerve and the sensory component of median nerve and sural nerve; 4) glycemic index, including fasting blood glucose levels (BSF), random blood glucose (BSR) levels, and HbA1c levels. Data were analyzed in SPSS v. 20. Chi-square and phi statistics and logistic regression analysis were run to analyze associations between diabetic neuropathy and time passed since diagnosis of diabetes and glycemic index. In total, 152 patients were recruited. One-half of those patients had neuropathy (76 patients) and the other half (76 patients) had normal nerve function. The mean (standard deviation [SD]) duration of diabetes was nine years (6.76), BSF levels 7.98 mmol/l (2.18), BSR 9.5 mmol/l (3.19), and HbA1c 6.5% (2.18). Logistic regression analysis predicted 87.5% of the model correctly. Duration since the diagnosis of diabetes and HbA1c levels were significantly associated with the diagnosis of neuropathy in diabetics. The presence of diabetic neuropathy was significantly associated with HbA1c levels and the duration of diabetes.


Linear acral pseudolymphomatous angiokeratoma of children with associated nail dystrophy.
Acral pseudolymphomatous angiokeratoma of children (APACHE) is a rare entity that typically occurs on the extremities of young females. Although linear arrangement of cutaneous lesions has been rarely reported, accompanying nail dystrophy has not been linked with this condition to our knowledge. We describe a case of linearly-oriented infiltrative papules and nodules on the index finger of a young female with associated onychodystrophy. Histology demonstrated a heavy lymphocytic infiltrate with plasma cells and proliferation of blood vessels consistent with APACHE. Our case is unique given the linear array of cutaneous lesions and associated nail dystrophy.


Enhancement of cyclosporin A-induced autologous graft-versus-host disease after peripheral blood stem cell transplantation by utilizing selected CD34(+) cells.
Although autologous graft-versus-host disease (GVHD) can be induced by administration of cyclosporin A (CsA) after peripheral blood stem cell transplantation (PBSCT), the incidence appears to be remarkably lower compared to the incidence after bone marrow transplantation. The reduced incidence of autologous GVHD after PBSCT may be attributed to peripheral regulatory cells that are transferred with the stem cell inoculum. To determine whether transplantation of CD34-selected peripheral blood stem cells (PBSCs) leads to potentiation of autologous GVHD, five patients with malignant lymphoma were transplanted with CD34-selected PBSCs, followed by administration of CsA and interferon (IFN)-gamma. Inducibility of autologous GVHD and autocytotoxic activities of peripheral blood mononuclear cells (PBMCs) after transplantation were assessed. All patients demonstrated prompt hematologic recovery. Cytotoxic activity of PBMCs against autologous lymphocytes was detectable in four of four patients analyzed during a limited period from days 14 to 34 post-transplant. An erythematous rash compatible with GVHD, confirmed by skin biopsy, developed in three of five patients. One of the three patients developed not only skin, but also gut and liver GVHD. Transplantation of the CD34-selected stem cell graft that does not accompany transfusion of regulatory cells may potentiate the inducibility of autologous GVHD by the administration of CsA and IFN-gamma.


Endoscopic polypectomy. Therapeutic and clinicopathologic aspects.
The problem of the malignant potential of neoplastic colonic polyps is being, in large measure, resolved by newly derived techniques. Now most polyps may be removed endoscopically using the fiberoptic colonoscope. The largest world experience is at the Beth Israel Medical Center in New York, where over 2000 polyps have been endoscopically removed without a single death and with but one complication requiring operative intervention. Laparotomy is now reserved for polyps not suitable for endoscopic resection or where a question of residual cancer exists. Experience with endoscopic resection has called for: 1) re-assessment of colonic polyps in terms of their malignant potential; and 2) clarification of the indications for laparotomy and bowel resection subsequent to or instead of endoscopic removal. Among all polypoid lesions 0.5 cm or greater in size in the Beth Israel series, a variety of pathologic types was encountered. If only the neoplastic polyps were considered, the incidence of "malignant change" was 10.5% for 855 polyps analyzed. There is, however, a need to clarify terminology and to differentiate between carcinoma in situ and invasive cancer whenever possible. Superficial cancers (carcinomas in situ) do not recur or metastasize and require no treatment other than polyp removal. When "invasive" cancer is present (4.5% of neoplastic polyps) or the lesion is a "polypoid carcinoma" each case must be individually evaluted. Criteria for diagnosis, gross morphological features suggesting cancerous change, and current management of "malignant" polyps are discussed. Colonoscopy is an important component of the followup program whether malignant polyps are resected endoscopically or by the transabdominal route.


Carrier ampholyte-free isoelectric focusing on a paper-based analytical device for the fractionation of proteins.
Isoelectric focusing plays a critical role in the analysis of complex protein samples. Conventionally, isoelectric focusing is implemented with carrier ampholytes in capillary or immobilized pH gradient gel. In this study, we successfully exhibited a carrier ampholyte-free isoelectric focusing on paper-based analytical device. Proof of the concept was visually demonstrated with color model proteins. Experimental results showed that not only a pH gradient was well established along the open paper fluidic channel as confirmed by pH indicator strip, the pH gradient range could also be tuned by the catholyte or anolyte. Furthermore, the isoelectric focusing fractions from the paper channel can be directly cut and recovered into solutions for post analysis with sodium dodecyl sulfate-polyacrylamide gel electrophoresis and matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry. This paper-based isoelectric focusing method is fast, cheap, simple and easy to operate, and could potentially be used as a cost-effective protein sample clean-up method for target protein analysis with mass spectrometry.


Migrating transformed MDCK cells are able to structurally polarize a voltage-activated K+ channel.
Cell migration of transformed renal epithelial cells (MDCK-F) depends-in addition to cytoskeletal mechanisms-on the polarized activity of a Ca2+-sensitive K+ channel in the rear part of the cells. However, because of the lack of specific markers for this channel we are not able to determine whether a polarized distribution of the channel protein underlies its functional polarization. To determine whether the migrating MDCK-F cells have retained the ability to target K+ channels to distinct membrane areas we stably transfected the cells with the voltage-dependent K+ channel Kv1.4. Stable expression and insertion into the plasma membrane could be shown by reverse transcription-PCR, genomic PCR, Western blot, and patch-clamp techniques, respectively. The distribution of Kv1.4 was assessed with indirect immunofluorescence by using conventional and confocal microscopy. These experiments revealed that Kv1.4 is expressed only in transfected cells where it elicits the typical voltage-dependent, rapidly inactivating K+ current. The Kv1.4 protein is clustered at the leading edge of protruding lamellipodia of migrating MDCK-F cells. This characteristic distribution of Kv1.4 provides strong evidence that migrating MDCK-F cells are able to insert ion channels into the plasma membrane in an asymmetric way, which reflects the polarization of migrating cells in the plane of movement. These findings suggest that not only epithelial cells and nerve cells, but also migrating cells, can create functionally distinct plasma membrane areas.


Enhanced nitrogen and carbon removal in natural seawater by electrochemical enrichment in a bioelectrochemical reactor.
Municipal and industrial wastewater discharges in coastal and marine environments are of major concern due to their high carbon and nitrogen loads and the resulted phenomenon of eutrophication. Bioelectrochemical reactors (BERs) for simultaneous nitrogen and carbon removal have gained attention owing to their cost efficiency and versatility, as well as the possibility of electrochemical enrich specific groups. This study presented a scalable two-chamber BERs using graphite granules as electrode material. BERs were inoculated and operated for 37 days using natural seawater with high concentrations of ammonium and acetate. The BERs demonstrated a maximum current density of 0.9 A m-3 and removal rates of 7.5 mg NH4+-N L-1 d-1 and 99.5 mg L-1 d-1 for total organic carbon (TOC). Removals observed for NH4+-N and TOC were 96.2% and 68.7%, respectively. The results of nutrient removal (i.e., ammonium, nitrate, nitrite and TOC) and microbial characterization (i.e., next-generation sequencing of the 16S rRNA gene and fluorescence in situ hybridization) showed that BERs operated with a poised cathode at -260 mV (vs. Ag/AgCl) significantly enriched nitrifying microorganisms in the anode and denitrifying microorganisms and planctomycetes in the cathode. Interestingly, the electrochemical enrichment did not increase the total number of microorganisms in the formed biofilms but controlled their composition. Thus, this work shows the first successful attempt to electrochemically enrich marine nitrifying and denitrifying microorganisms and presents a technique to accelerate the start-up process of BERs to remove dissolved inorganic nitrogen and total organic carbon from seawater.


A case of adult B lymphoblastic leukemia with ider(9)(q10)t(9;22)(q34;q11.2) and der(19)t(1;19)(q23;p13.3).
In B lymphoblastic leukemia/lymphoma (B-ALL/LBL), t(9;22)(q34;q11.2) and t(1;19)(q23;p13.3) are recurrent cytogenetic abnormalities. The concurrent occurrence of both abnormalities is very rare, and only 3 cases have been previously reported. Here, we report a case of adult B-ALL with ider(9)(q10)t(9;22)(q34;q11.2) and der(19)t(1;19)(q23;p13.3). A literature review revealed that ider(9) (q10)t(9;22) is a rare variant of t(9;22) with a deletion of the short arm of chromosome 9. Fifteen cases of ider(9)(q10)t(9;22) have been reported. This abnormality is specific to precursor B-lymphoid neoplasms, such as B-ALL or B-lymphoid blast phase of CML, and is associated with disease progression or short survival. The cytogenetic abnormality t(1;19) is also specific to B-ALL. In most instances of t(1;19), TCF3 is fused to PBX1; however, a few cases have identical translocations but no TCF3-PBX1 fusion, as was observed in our patient. We describe the first case of ider(9)(q10)t(9;22) in combination with TCF3-PBX1 negative t(1;19). The patient underwent imatinib therapy in addition to intensive chemotherapy, but failed to achieve remission.


Safety Assessment of Two Hybrid Instrumentation Techniques in a Dental Student Endodontic Clinic: A Retrospective Study.
The aim of this study was to retrospectively assess the safety potential of a hybrid technique combining nickel-titanium (NiTi) reciprocating and rotary instruments by third- and fourth-year dental students in the predoctoral endodontics clinic at one U.S. dental school. For the study, 3,194 root canal treatments performed by 317 dental students from 2012 through 2015 were evaluated for incidence of ledge creation and instrument separation. The hybrid reciprocating and rotary technique (RRT) consisted of a glide path creation with stainless steel hand files up to size 15/02, a crown down preparation with a NiTi reciprocating instrument, and an apical preparation with NiTi rotary instruments. The control was a traditional rotary and hand technique (RHT) that consisted of the same glide path procedure followed by a crown down preparation with NiTi rotary instruments and an apical preparation with NiTi hand instruments. The results showed that the RHT technique presented a rate of ledge creation of 1.4% per root and the RRT technique was 0.5% per root (p<0.05). Three stainless steel hand files separated: two in the RHT group and one in the RRT group. There was no separation of any NiTi file in any of the techniques. The use of the reciprocating and rotary technique for root canal instrumentation by these dental students provided good safety. This hybrid technique offered a low rate of ledge creation along with no NiTi instrument separation.


A unique life history among tetrapods: an annual chameleon living mostly as an egg.
The approximately 28,300 species of tetrapods (four-limbed vertebrates) almost exclusively have perennial life spans. Here, we report the discovery of a remarkable annual tetrapod from the arid southwest of Madagascar: the chameleon Furcifer labordi, with a posthatching life span of just 4-5 months. At the start of the active season (November), an age cohort of hatchlings emerges; larger juveniles or adults are not present. These hatchlings grow rapidly, reach sexual maturity in less than 2 months, and reproduce in January-February. After reproduction, senescence appears, and the active season concludes with population-wide adult death. Consequently, during the dry season, the entire population is represented by developing eggs that incubate for 8-9 months before synchronously hatching at the onset of the following rainy season. Remarkably, this chameleon spends more of its short annual life cycle inside the egg than outside of it. Our review of tetrapod longevity (>1,700 species) finds no others with such a short life span. These findings suggest that the notorious rapid death of chameleons in captivity may, for some species, actually represent the natural adult life span. Consequently, a new appraisal may be warranted concerning the viability of chameleon breeding programs, which could have special significance for species of conservation concern. Additionally, because F. labordi is closely related to other perennial species, this chameleon group may prove also to be especially well suited for comparative studies that focus on life history evolution and the ecological, genetic, and/or hormonal determinants of aging, longevity, and senescence.


Development of dextran derivatives with cytotoxic effects in human urinary bladder cancer cell lines.
In a previous study we reported on a new approach describing intravesical instillation of charged dextran in patients with superficial bladder carcinoma. The cationic derivative showed a strong tumor-selective accumulation. To develop this approach, the present study investigates the cytotoxic effect of cationic dextran derivatives on two urinary bladder cancer cell lines (J82 and 5637). The dextran conjugates were prepared by periodate activation and subsequent coupling by reductive amination. A fluorimetric cytotoxicity assay (FMCA) was used for the cytotoxicity assay. The tumor cells were seeded into 96-well microtiter plates and different cationic dextran derivatives were added and incubated for 72 hours. The results showed that cationic epirubicin-dextran had a clear inhibitory effect on the growth in both cell lines (40-95% growth inhibition). The corresponding values for epirubicin (the reference) was 90-100% inhibition. Interestingly, cationic dextran had, by itself, a growth inhibitory effect. This cytotoxic effect could be strongly enhanced to be almost equal to the reference by changing the cationic sidegroup to aminohexane. Dextran alone showed no effect. The finding that cationic dextran by itself can be made cytotoxic, together with its capacity to accumulate in superficial bladder cancer, suggests possibilities for new therapeutic constructs. Cationic dextran with different cationic side-groups and in combination with cytotoxic drugs will be studied further. The cytotoxic mechanism needs to be elucidated.


Oleanolic Acid Alters Multiple Cell Signaling Pathways: Implication in Cancer Prevention and Therapy.
Nowadays, much attention has been paid to diet and dietary supplements as a cost-effective therapeutic strategy for prevention and treatment of a myriad of chronic and degenerative diseases. Rapidly accumulating scientific evidence achieved through high-throughput technologies has greatly expanded the understanding about the multifaceted nature of cancer. Increasingly, it is being realized that deregulation of spatio-temporally controlled intracellular signaling cascades plays a contributory role in the onset and progression of cancer. Therefore, targeting regulators of oncogenic signaling cascades is essential to prevent and treat cancer. A plethora of preclinical and epidemiological evidences showed promising role of phytochemicals against several types of cancer. Oleanolic acid, a common pentacyclic triterpenoid, is mainly found in olive oil, as well as several plant species. It is a potent inhibitor of cellular inflammatory process and a well-known inducer of phase 2 xenobiotic biotransformation enzymes. Main molecular mechanisms underlying anticancer effects of oleanolic acid are mediated by caspases, 5' adenosine monophosphate-activated protein kinase, extracellular signal-regulated kinase 1/2, matrix metalloproteinases, pro-apoptotic Bax and bid, phosphatidylinositide 3-kinase/Akt1/mechanistic target of rapamycin, reactive oxygen species/apoptosis signal-regulating kinase 1/p38 mitogen-activated protein kinase, nuclear factor-κB, cluster of differentiation 1, CKD4, s6k, signal transducer and activator of transcription 3, as well as aforementioned signaling pathways . In this work, we critically review the scientific literature on the molecular targets of oleanolic acid implicated in the prevention and treatment of several types of cancer. We also discuss chemical aspects, natural sources, bioavailability, and safety of this bioactive phytochemical.


Cost-utility analysis of trabecular micro-bypass stents (TBS) in patients with mild-to-moderate open-angle Glaucoma in Italy.
Glaucoma is a disease characterized by progressive damage of the optic nerve. Several therapeutic options are available to lower intraocular pressure (IOP). In primary open-angle glaucoma (POAG) patients with inadequate IOP control (or controlled with multiple medical therapies or for whom medical therapy is contraindicated), the implantation of micro-invasive glaucoma surgery devices (MIGS) and concomitant cataract surgery has proved to be more effective in reducing intraocular pressure (IOP), as compared to cataract surgery alone. The objective of this study was to assess the cost-effectiveness of iStent inject® device with concurrent cataract surgery vs. cataract surgery alone, in patients with mild-to-moderate POAG, adopting the Italian National Health Service (NHS) perspective. Simulation of outcomes and costs was undertaken using a Markov model with 4 health states and one-month cycles, that is used to simulate the prognosis of these patients. Efficacy data were obtained from the randomized clinical trial (RCT). A lifetime horizon was adopted in the analysis. A discount rate of 3.5% was applied to both costs and effects. The Italian National Healthcare Service (NHS) perspective was considered, therefore only healthcare direct costs (acquisition of main interventions and subsequent procedures; medications; monitoring and follow-up; adverse events). Model robustness was tested through sensitivity analyses. Results of the base-case analysis showed that the total lifetime costs were higher in the iStent inject® + concurrent cataract surgery, compared with the cataract surgery alone group (€8368.51 vs. €7134.71 respectively). iStent inject® + concurrent cataract surgery was cost-effective vs. cataract surgery alone, with an incremental cost-effectiveness ratio of €13,037.01 per quality-adjusted life year (QALY) gained. Both one-way deterministic and probabilistic sensitivity analyses confirmed robustness of base-case results. The cost-effectiveness accessibility curve (CEAC) showed that iStent inject® + cataract surgery would have a 98% probability of being cost-effective, compared to cataract surgery alone, when the willingness to pay (WTP) is equal to €50,000 per QALY gained. The results of the cost-utility analysis confirm that iStent inject® + cataract surgery is a cost-effective option for the treatment of patients affected by mild-to-moderate POAG, compared with cataract surgery alone, when evaluated from the Italian NHS perspective.


LKB1 acts as a critical brake for the glucagon-mediated fasting response.
As important as the fasting response is for survival, an inability to shut it down once nutrients become available can lead to exacerbated disease and severe wasting. The liver is central to transitions between feeding and fasting states, with glucagon being a key initiator of the hepatic fasting response. However, the precise mechanisms controlling fasting are not well defined. One potential mediator of these transitions is liver kinase B1 (LKB1), given its role in nutrient sensing. Here, we show LKB1 knockout mice have a severe wasting and prolonged fasting phenotype despite increased food intake. By applying RNA sequencing and intravital microscopy, we show that loss of LKB1 leads to a dramatic reprogramming of the hepatic lobule through robust up-regulation of periportal genes and functions. This is likely mediated through the opposing effect that LKB1 has on glucagon pathways and gene expression. Conclusion: Our findings show that LKB1 acts as a brake to the glucagon-mediated fasting response, resulting in "periportalization" of the hepatic lobule and whole-body metabolic inefficiency. These findings reveal a mechanism by which hepatic metabolic compartmentalization is regulated by nutrient-sensing.


Nonlinear dynamics of cell orientation.
The nonlinear dependence of cellular orientation on an external, time-varying stress field determines the distribution of orientations in the presence of noise and the characteristic time, tauc, for the cell to reach its steady-state orientation. The short, local cytoskeletal relaxation time distinguishes between high-frequency (nearly perpendicular) and low-frequency (random or parallel) orientations. However, tauc is determined by the much longer, orientational relaxation time. This behavior is related to experiments for which we predict the angle and characteristic time as a function of frequency.