Discontinuation of Antipsychotics in Nursing Home Patients With Dementia.
The authors assessed the consequences of stopping antipsychotic medication in nursing home patients with dementia, as mandated by federal regulations (OBRA 87). They studied three patient groups: 1) a group ("clinical judgment") whose antipsychotics were discontinued at the discretion of their physicians; 2) a group ("empirical") with mandated cessation of antipsychotics in the facility; and 3) a comparison group of patients not receiving medication. The primary outcome measure was the necessity to resume antipsychotic or other psychotropic medication ("failure"). Also, assessments of behavior, function, neurologic status, and cognition were performed by blind raters. The failure rate in the empirical withdrawal group was 50%, 10 times that of the clinical judgment group. Among failures, the most striking result was increased verbal and physical aggression. No failures occurred in the comparison group. There were no benefits of antipsychotic withdrawal in terms of neurological performance, functional status, or cognition.


Systemic lupus erythematosus in Saudi children: long-term outcomes.
To report the long-term outcome of Saudi children with systemic lupus erythematosus (SLE). Charts of all children with SLE treated between 1990 and 2010 at King Faisal Specialist Hospital and Research Center Riyadh, were reviewed. The long-term outcome measured by pediatric adaptation of the Systemic Lupus International Collaborating Clinics American College of Rheumatology Damage Index (pSDI) and death related to SLE were determined. The data included: gender, age at disease onset, clinical features and treatment at last follow-up visit. One hundred and fifty-two patients (129 girls and 23 boys) were included. The mean age at onset of SLE was 8.8 ± 2.6 years, while the mean age at diagnosis was 9.5 ± 2.6 years and the mean disease duration was 7.5 ± 4.6 years. All patients were treated with corticosteroid and immunosuppressive drugs. Eighty (52.6%) patients had damage with a mean SDI score of 1.3 ± 1.7. Damage accrual was mostly in the growth (26.8%), renal (17.1%) and neuropsychiatric (15.8%) domains. Due to progressive renal disease, 14 patients required dialysis; five of them underwent renal transplant. There were nine deaths related to SLE, eight of them due to infection. Based on logistic regression, patient disease damage was significantly associated with young age at disease onset and long disease duration. Similarly, death related to SLE was influenced by early-onset disease. In contrast, gender, disease duration and therapy did not affect the suggested outcome measures. Our results are comparable to reports from other tertiary centers. Early-onset disease probably influences the long-term outcome of SLE in children. Infection remains an important cause of death in children with SLE.


[Basal fecal fermentation and with lactulose in patients with flatulence].
Determinations of the fecal fermentation in subjects may be very useful to know the fermentative capacity of his colonic bacteria. Determinations of basal fecal fermentation (FFB) and fecal fermentation with lactulose (FFL) were done in 30 normal subjects and 126 patients with flatulence, especially meteorism. The media +/- s.d. of FFB was significantly higher in the normal subjects than in the patients with flatulence (1.82 +/- 1.55 vs. 1.24 +/- 1.40 ml of gas/24 h; P: 0.015). On the contrary, in patients with flatulence the obtained media +/- s.d. of FFL and of the differences between FFL and FFB (FFL-FFB) were significantly and markedly higher than in the normal subjects (respectively: 8.84 +/- 5.55 vs. 5.72 +/- 3.72 ml of gas/24 h, P: 0.004; and 7.60 +/- 5.05 vs. 3.91 +/- 3.22 ml of gas/24 h, P<0.00001). The obtained results seem to indicate that patients with flatulence tend to have a colonic flora with high fermentative capacity.


A Comparison of Clinical Outcomes between Early Cervical Spine Stabilizer Training and Usual Care in Individuals following Anterior Cervical Discectomy and Fusion.
Early physical therapy (PT) with specific stabilization training has been shown to benefit individuals after lumbar spinal surgery but has not been studied in patients after cervical spine surgery. The primary purpose of this study was to compare clinical outcomes between early cervical spine stabilizer (ECS) training and usual care (UC) in patients after anterior cervical discectomy and fusion (ACDF) surgery. The secondary purpose was to determine test-retest reliability of strength and endurance tests of cervical spinal stabilizers in this patient population. Forty participants who were scheduled for ACDF surgery were randomized into either the ECS group or the UC group. After surgery, participants received their assigned group intervention during their hospital stay and continued their assigned intervention for 12 weeks. All participants had phone follow-ups twice during the first 6 weeks to address questions or problems. Clinical outcome measures including pain level using the Numeric Pain Rating Scale (NPRS), disability level using the Neck Disability Index (NDI), Craniocervical Flexor Strength (CCF-S), and Craniocervical Flexor Endurance (CCF-E) were collected three times: before surgery and 6 and 12 weeks after surgery. Test-retest reliability was assessed in the first 10 participants. There was no significant interaction between the groups over time for any of the outcome measures. However, all participants made significant improvements in all four outcome measures at 6 and 12 weeks post surgery. The results showed good-to-excellent test-retest reliability for the CCF-S and CCF-E tests. Both ECS training and UC resulted in the same amount of improvement at 6 and 12 weeks; therefore, both therapy approaches appear to have similar and positive effects on patients in their first 3 months of recovery after ACDF. Both the CCF-S and CCF-E tests can be used reliably to assess the strength and endurance of the cervical spinal stabilizers for patients after ACDF surgery. The study was registered with the ClinicalTrials.gov (NIH, U.S. National Library of Medicine, identifier # NCT01519115) Protocol Registration system.


Successful restructuring: maximizing training dollars.
Data regarding the cost of staff training associated with restructuring are scarce and incomplete, with little measurement of how staff performed after training. Effectiveness of staff education efforts are hampered by staff resistance to change, dysfunctional interdisciplinary team work, and existing system "glitches." The key criteria for successful education efforts related to restructuring are: development of measurable desired outcomes of training efforts, determination of solution appropriateness and resource needs, the thoughtful timing of interventions, and a high level of ongoing organizational support. Changes in teamwork effectiveness can be measured by examining variances in quality outcomes, timely and appropriate discharge planning, and resource cost measures such as use of overtime and absenteeism. Recommendations for effective use of training dollars include acknowledging resistance and providing forums which permit time (and a process) for re-education.


Multimode two-dimensional vibronic spectroscopy. II. Simulating and extracting vibronic coupling parameters from polarization-selective spectra.
Experimental demonstrations of polarization-selection two-dimensional Vibrational-Electronic (2D VE) and 2D Electronic-Vibrational (2D EV) spectroscopies aim to map the magnitudes and spatial orientations of coupled electronic and vibrational coordinates in complex systems. The realization of that goal depends on our ability to connect spectroscopic observables with molecular structural parameters. In this paper, we use a model Hamiltonian consisting of two anharmonically coupled vibrational modes in electronic ground and excited states with linear and bilinear vibronic coupling terms to simulate polarization-selective 2D EV and 2D VE spectra. We discuss the relationships between the linear vibronic coupling and two-dimensional Huang-Rhys parameters and between the bilinear vibronic coupling term and Duschinsky mixing. We develop a description of the vibronic transition dipoles and explore how the Hamiltonian parameters and non-Condon effects impact their amplitudes and orientations. Using simulated polarization-selective 2D EV and 2D VE spectra, we show how 2D peak positions, amplitudes, and anisotropy can be used to measure parameters of the vibronic Hamiltonian and non-Condon effects. This paper, along with the first in the series, provides the reader with a detailed description of reading, simulating, and analyzing multimode, polarization-selective 2D EV and 2D VE spectra with an emphasis on extracting vibronic coupling parameters from complex spectra.


Quantitative relationships between steroid structure and binding to putative progesterone receptors.
Relationships between chemical structure of androst-4-en-3-one derivatives and their affinity for putative progesterone receptors are described. The binding affinity for 55 derivatives can be expressed by the equation log relative binding affinity (rabbit receptor) = 1.79 + 0.18 (+/-0.11) pia + 1.45 (+/-0.21) pib + 0.010 (+/-0.002) (surface area in hydrophobic pockets) - 0.012 (+/-0.003) (surface area out of hydrophobic pockets) - 0.99 (+/-0.21) MK - 0.33 (+/-0.08) (conformational changes). For this equation, r=0.88. The equation successfully predicts the affinities of other compounds in the literature. The importance of the surface area terms is discussed.


Quantitative assessment of the spatial heterogeneity of tumor-infiltrating lymphocytes in breast cancer.
Tumor-infiltrating lymphocyte (TIL) count in breast cancer carries prognostic information and represents a potential predictive marker for emerging immunotherapies. However, the distribution of the lymphocyte subpopulations is not well defined. The goals of this study were to examine intratumor heterogeneity in TIL subpopulation counts in different fields of view (FOV) within each section, in different sections from the same biopsy, and between biopsies from different regions of the same cancer using quantitative immunofluorescence (QIF). We used multiplexed QIF to quantify cytokeratin-positive epithelial cells, and CD3-positive, CD8-positive and CD20-positive lymphocytes in tissue sections from multiple biopsies obtained from different areas of 31 surgically resected primary breast carcinomas (93 samples total). Log2-transformed QIF scores or concordance and variance component analyses with linear mixed-effects models were used. Cohen's kappa index [k] of high versus low scores, defined as above and below the median, was used to measure sample similarity between areas. We found a strong positive correlation between CD3 and CD8 levels across all patients (Pearson correlation coefficient [CC] = 0.827). CD3 and CD8 showed a weaker but significant association with CD20 (CC = 0.446 and 0.363, respectively). For each marker, the variation between different FOVs in the same section was higher than the variation between sections or between biopsies of the same cancer. The intraclass correlation coefficients (ICC) were 0.411 for CD3, 0.324 for CD8, and 0.252 for CD20. In component analysis, 66-69 % of the variance was attributable to differences between FOVs in the same section and 30-33 % was due to differences between biopsies from different areas of the same cancer. Section to section differences were negligible. Concordance for low versus high marker status assignment in single biopsies compared to all three biopsies combined yielded k = 0.705 for CD3, k = 0.655 for CD8, and k = 0.603 for CD20. T and B lymphocytes show more heterogeneity across the dimensions of a single section than between different sections or regions of a given breast tumor. This observation suggests that the average lymphocyte score from a single biopsy of a tumor is reasonably representative of the whole cancer.


Krüppel-like factor 4 prevents centrosome amplification following gamma-irradiation-induced DNA damage.
Centrosome duplication is a carefully controlled process in the cell cycle. Previous studies indicate that the tumor suppressor, p53, regulates centrosome duplication. Here, we present evidence for the involvement of the mammalian Krüppel-like transcription factor, KLF4, in preventing centrosome amplification following DNA damage caused by gamma-irradiation. The colon cancer cell line HCT116, which contains wild-type p53 alleles (HCT116 p53+/+), displayed stable centrosome numbers following gamma-irradiation. In contrast, HCT116 cells null for the p53 alleles (HCT116 p53-/-) exhibited centrosome amplification after irradiation. In the latter cell line, KLF4 was not activated following gamma-irradiation due to the absence of p53. However, centrosome amplification could be suppressed in irradiated HCT116 p53-/- cells by conditional induction of exogenous KLF4. Conversely, in a HCT116 p53+/+ cell line stably transfected with small hairpin RNA (shRNA) designed to specifically inhibit KLF4, gamma-irradiation induced centrosome amplification. In these cells, the inability of KLF4 to become activated in response to DNA damage was directly associated with an increase in cyclin E level and Cdk2 activity, both essential for regulating centrosome duplication. Cotransfection experiments showed that KLF4 overexpression suppressed the promoter activity of the cyclin E gene. The results of this study demonstrated that KLF4 is both necessary and sufficient in preventing centrosome amplification following gamma-radiation-induced DNA damage and does so by transcriptionally suppressing cyclin E expression.


Craniopharyngiomas--the utility of contrast medium enhancement for MR imaging at 1.5 T.
To evaluate the efficacy of i.v. contrast medium administration in MR imaging at 1.5 T in patients with craniopharyngiomas, MR studies of 10 men and 6 women with pathologically proven craniopharyngiomas were made. The MR images were obtained as 3- to 5-mm-thick coronal (n = 13) or axial (n = 3) Tl-weighted images (T1WI) prior to and following i.v. Gd-DTPA administration. Proton density- (PD) and T2-weighted images (T2WI) were also obtained. Conspicuity of tumor margins, cystic versus solid components, size, location and effect upon adjacent structures were separately characterized in all imaging sequences. In 6 patients contrast medium-enhanced T1WI. PD and T2WI demonstrated cystic tumor components not seen on unenhanced T1WI. There were significant differences (p < 0.004) on 2-tailed Student's t-test comparing tumor conspicuity on contrast medium-enhanced T1WI with unenhanced T1WI, PD and T2WI. Optimal tumor delineation on MR imaging of patients with craniopharyngiomas justifies the use of i.v. contrast medium.


Effect of transcranial magnetic stimulation in combination with citalopram on patients with post-stroke depression.
Amelioration of depression in patients with post-stroke depression (PSD) remains challenging. The primary vision was to explore the effect of transcranial magnetic stimulation (TMS) in combination with citalopram on patients with PSD. One hundred eligible patients who were diagnosed with PSD were recruited and randomly assigned to the control group (n = 50) or the TMS group (n = 50). The controls were given citalopram (10 mg/d for consecutive 8 weeks), while, in addition to citalopram, patients in the TMS group were also given TMS at 5 Hz once a workday for 8 weeks. The primary outcome was patient depression status as reflected by 17-item Hamilton Rating Scale for Depression (HAMD-17) score, and the secondary outcome was patient neuropsychological score determined by Mini-Mental State Examination (MMSE) and Wisconsin Card Sorting Test (WCST). Patients treated with TMS in combination with citalopram had a drastic decrease in HAMD-17 score during treatment. Bigger changes in HAMD-17 score between baseline and 2 weeks as well as between baseline and 8 weeks in the TMS group were observed (P < 0.01). Patients in both groups had increased MMSE scores after treatment. Data of WCST revealed patients with TMS treatment completed more categories (P < 0.01) and had a lower RPP in comparison to patients in the control group (P < 0.0001). Additionally, TMS in combination with citalopram strikingly improved patients' MMSE scores when compared with those taking citalopram alone. Last, there was no striking difference in side effects between the two groups (P > 0.05). Our study found TMS in combination with citalopram is conducive to improving depression status and neuropsychological function, which holds great promise for treating PSD.


[Use of oximinoiminopyrrazoline esters in the synthesis of solids phase peptides: synthesis of bradykinin].
Since oximinyliminopyrrazoline ester (OPmp) present a peculiar characteristic in the omogenous peptide synthesis, the use of them, also in the synthesis of bradikinine by the solid phase technique, was duly taken into consideration and tried out. This synthesis was achieved by employing N-protected amino acid OPmp esters containing a methoxycarbonyl or a benzylaminocarbonyl as the acyl function in position 5 of the pyrazoline ring. No significant differences were found in the reactivity of such derivatives in respect of OPmp esters containing the benzyloxycarbonylglycyl moiety. The biological activity of the synthetized braikinine is similar to that of a sample of natural "standard".


Effects of mindfulness-based therapy for patients with breast cancer: A systematic review and meta-analysis.
To quantify the effects of mindfulness-based therapy (MBT) on physical health, psychological health and quality of life (QOL) in patients with breast cancer. Studies were identified through a systematic search of six electronic databases. Randomized control trials (RCTs) examining the effects of MBT, versus a control group receiving no intervention on physical health, psychological health and QOL in breast cancer patients were included. Two authors independently assessed the methodological quality of included studies using a quality-scoring instrument developed by Jadad et al. and extracted relevant information according to a predesigned extraction form. Data was analysed using the Cochrane Collaboration's Revman5.1. Finally, seven studies involving 951 patients were included. While limited in power, the results of meta-analysis indicated a positive effect of MBT in reducing anxiety [SMD -0.31, 95% CI -0.46 to -0.16, P<0.0001], depression[SMD -1.13, 95% CI -1.85 to -0.41, P=0.002], fear of recurrence[SMD -0.71, 95% CI -1.05 to -0.38, P<0.0001], and fatigue[SMD -0.88, 95% CI -1.71 to -0.05, P=0.04] associated with breast cancer, and improving emotional well-being [SMD 0.39, 95% CI 0.19-0.58, P=0.0001], physical function[SMD 0.42, 95% CI 0.19-0.65, P=0.0004], and physical health [SMD 0.31, 95% CI 0.08-0.54, P=0.009] in these patients. Although the effects on stress, spirituality, pain and sleep were in the expected direction, they were not statistically significant (P>0.05). Moreover, there is limited evidence from a narrative synthesis that MBT can improve QOL of breast cancer patients. The present data indicate that MBT is a promising adjunctive therapy for patients with breast cancer. Due to some methodological flaws in the literature, further well-designed RCTs with large sample sizes are needed to confirm these preliminary estimates of effectiveness.


Problems after ileo-pouch anal anastomosis for ulcerative colitis. How can we prevent it? What can we do?
During the last 10 years (1982-1992) 370 patients have had a pelvic pouch constructed in the Colorectal Unit at the Department of Surgery II, Sahlgrenska Hospital. The complications and the eventual outcome in 307 patients (median follow-up 5.5 years ranging from 1.5 to 11 years) have been analysed. The overall complication rate was 22%. Anastomotic leaks, anal ulcerations or fissures and strictures (13%) and small bowel obstruction (5%) were the most common followed by ileostomy-related complications (2%). Re-laparatomy was required in 10%. Most anastomosis-related complications were successfully managed by prolonged ileostomy diversion combined with local procedures. The anastomotic leaks all proved to be radiologically healed at the time of ileostomy closure. Three of 16 patients who had had radiological leaks developed complications subsequently, but all could be successfully managed. In contrast, 6 of 15 patients in whom clinical leaks healed initially developed complications that eventually resulted in failure. The overall late complication rate was 22%. The most common complications were anastomotic stricturing (4%), small bowel obstruction (5%) and poor pouch function (pelvic pain, high evacuation frequency and other functional imperfections) (6%). Anal abscess, fistula or pouch-vaginal fistula were uncommon, however. While laying open of simple anal fistula and dilation of stenosis during anaesthesia were sometimes successful, re-laparotomy with redo of the pouch-anal anastomosis was needed for successful treatment of grossly fibrotic strictures, complex pouch-vaginal fistulae and poorly functioning pouches.(ABSTRACT TRUNCATED AT 250 WORDS)


Adverse birth outcome: a comparative analysis between cesarean section and vaginal delivery at Felegehiwot Referral Hospital, Northwest Ethiopia: a retrospective record review.
Some studies favor elective cesarean delivery, and other surveys benefit vaginal delivery, while others emphasize that the quality of care during labor, birth, and immediate postpartum period plays a great role than the route of delivery. However, little information is locally available regarding the incidences of adverse birth outcome with respect to the route of delivery. This study was a retrospective analysis of eligible patient records that included 3,003 pregnant women who had undergone either cesarean or vaginal delivery from July 1, 2012, to June 31, 2013. Pretested questionnaire was used to collect the data. The completeness and consistency of the data were checked, cleaned, and double entered to EPI-INFO 3.5.2 and analyzed with SPSS V20. Independent sample t-test and chi-square test were conducted to compare the outcome of vaginal delivery and cesarean section (CS) using index variables. Significance was taken at P<0.05. Among the enrolled women, 760 mothers had CS delivery and the remaining 2,243 mothers delivered vaginally. Children born through CS (mean =6.83, standard deviation =1.31) had a significantly lower first-minute Apgar score than those in the vaginal delivery group (mean =7.19, standard deviation =1.18, P=0.001). Similarly, the observed respiratory distress syndrome (c2=0.09, P=0.793) and neonatal transfer rate to neonatal intensive care unit (c2=0.086, P=0.766) were more in neonates delivered by CS than those in the vaginally delivered group. Besides, the observed neonatal death (c2=0.675, P=0.411) and maternal death (c2= 8.878, P=0.003) were higher among CS deliveries compared with vaginal deliveries. Neonatal and maternal morbidity and mortality appear to be more in CS than in vaginal delivery. Therefore, decision to perform CS should be based on clear, compelling, and well-supported justifications.


Right Diaphragmatic Rupture: A Case Report of a Rare Surgical Trauma Emergency.
Diaphragmatic injuries, particularly on the right side, are a rare yet challenging clinical scenario, especially when associated with other injuries. We present the case of a 38-year-old male patient who sustained a fall from a significant height, resulting in blunt abdominal trauma, chest injuries, right-side diaphragmatic injury, a grade 4 liver injury, and fractures of the right ribs, right femur, and pelvis. The patient also suffered a lung laceration with hemopneumothorax. The clinical team managed these injuries through a video-assisted thoracoscopy, laparotomy, and primary repair of the diaphragmatic rupture. The postoperative course was complicated by a low-output bile leak and infection of the orthopedic surgical wound, but these were effectively managed, and the patient showed a steady recovery. This case underscores the complexity of managing traumatic injuries that span multiple body regions and systems, requiring a coordinated, multidisciplinary approach. It also highlights the critical role of timely intervention and appropriate surgical strategies in the successful recovery of patients from complex traumas.


Prediction of acute cardiac rejection by changes in left ventricular volumes.
Sixteen patients underwent heart transplantation (11 orthotopic, five heterotopic). Monitoring for acute rejection was by both endomyocardial biopsy (EMB) and multigated equilibrium blood pool scanning with technetium 99m-labelled red blood cells. From the scans information was obtained on left ventricular volumes (stroke, end-diastolic, and end-systolic), ejection fraction, and heart rate. Studies (208) were made in the 16 patients. There was a highly significant correlation between the reduction in stroke volume and end-diastolic volume (and a less significant correlation in end-systolic volume) and increasing acute rejection seen on EMB. Heart rate and ejection fraction did not correlate with the development of acute rejection. Correlation of a combination of changes in stroke volume and end-diastolic volume with EMB showed a sensitivity of 85% and a specificity of 96%. Radionuclide scanning is therefore a useful noninvasive tool for monitoring acute rejection.


Midodrine. A new agent in the management of idiopathic orthostatic hypotension and Shy-Drager syndrome.
Five patients with idiopathic orthostatic hypotension, two of whom had central nervous system manifestations (Shy-Drager syndrome), were treated with midodrine, an investigational alpha-adrenergic agonist, in a dosage of 2.5 to 5 mg three times daily. Significant improvement was observed in the standing systolic and diastolic blood pressures at the end of 1 week of therapy in all patients and has been maintained for 10 to 15 months in all patients. No symptomatic side effects were noted. Supine systolic hypertension occurred in two patients and was treated with small doses of metoprolol.


[Swine blood leukocytes--new source of production of inferferon active in human cells].
Swine blood leukocytes have first been found capable of producing interferon the antiviral activity in human cells of which is comparable to that of native human leukocyte interferon. The influence of various factors on production of porcine leukocyte interferon active in human cells were studied. Thus, when serum was substituted with MAF in the medium used for leukocyte cultivation the titer of the produced interferon increased 4--16-fold and the content of protein impurities in the preparation decreased 10-fold or more. Marked individual interferon-producing capacity of blood leukocytes from different swine and seasonal variations in the level of this capacity were established. The optimal conditions for porcine leukocyte interferon production are: the use of leukocytes in the first few hours after bleeding of the animals; leukocyte concentration in the medium 10 million cells per 1 ml; medium 199 with 10% MAF; New-castle disease virus as interferon inducer in a dose of 10--100 CPD50 per cell. Priming of leukocytes with interferon enhanced their interferon-synthesizing capacity 2--8-fold. This new source of interferon production is readily available, and interferon is useful for public health and veterinary needs.


Orthopedic Manifestations and Post-COVID-19 Infection.
It's been widely reported that the new coronavirus has adverse effects on the musculoskeletal system. The primary goal of this study is to establish the frequency of musculoskeletal complaintswith extended COVID syndrome. This retrospective cohort research examined the occurrence of musculoskeletal problems in patients with chronic COVID-19 syndrome. About 100 COVID-19patients tested positive, of which 27 (27.0%) had a minimum of one orthopedic impairment. Patients with orthopedic conditions were significantly younger than those without (53.7 years vs. 58.1 years, p = 0.003), and their incidence was significantly higher in obese than non-obese patients (p = 0.022). Furthermore, patients with diabetes had significantly more orthopedic symptoms than those with cardiac or pulmonary complications. According to our research, patients who are obese or diabetic have a higher probability of experiencing musculoskeletal symptoms when infected with COVID-19. Additionally, analysis is needed to determine whether these orthopedic conditions persist during active disease and post-infection.


A peculiar site of chondroma: the epiglottis.
Chondroma of the laryngeal cartilage is an uncommon benign cartilaginous neoplasm. The commonest location is the posterior lamina of the cricoid cartilage, followed by the thyroid cartilage. The occurrence of chondroma in the epiglottis is extremely rare. Depending on the size and location of epiglottic chondroma the clinical manifestations are variable and include a lump in the neck, difficulty in swallowing fluids and dyspnea. In this study, an additional rare case of chondroma arising in the epiglottis is reported. The mass was located over the tip of the epiglottis and caused no significant clinical manifestations except for a foreign body sensation in the throat. Endoscopic excision with an adequate free margin was achieved via suspension laryngoscopy under general anesthesia with intubation. The patient was disease-free during a 1-year follow-up period. We present this case to highlight the occurrence of this rare benign lesion in the epiglottis, and stress that it should not be neglected in the differential diagnosis of an epiglottic mass. Conservative surgical excision is the initial treatment of choice and long-term follow-up is necessary.


Citrobacter amalonaticus Y19 for constitutive expression of carbon monoxide-dependent hydrogen-production machinery.
Citrobacter amalonaticus Y19 is a good biocatalyst for production of hydrogen (H2) from oxidation of carbon monoxide (CO) via the so-called water-gas-shift reaction (WGSR). It has a high H2-production activity (23.83 mmol H2 g-1 cell h-1) from CO, and can grow well to a high density on various sugars. However, its H2-production activity is expressed only when CO is present as an inducer and in the absence of glucose. In order to avoid dependency on CO and glucose, in the present study, the native CO-inducible promoters of WGSR operons (CO dehydrogenase, CODH, and CODH-dependent hydrogenase, CO-hyd) in Y19 were carefully analyzed and replaced with strong and constitutive promoters screened from Y19. One engineered strain (Y19-PR1), selected from three positive ones after screening ~10,000 colonies, showed a similar CO-dependent H2-production activity to that of wild-type Y19, without being affected by glucose and/or CO. Compared with wild-type Y19, transcription of the CODH operon in Y19-PR1 increased 1.5-fold, although that of the CO-hyd operon remained at a similar level. To enhance the activity of CO-Hyd in Y19-PR1, further modifications, including an increase in gene copy number and engineering of the 5' untranslated region, were attempted, but without success. Convenient recombinant Y19-PR1 that expresses CO-dependent H2-production activity without being limited by CO and glucose was obtained.


Staphylococcus aureus protects its immune-evasion proteins against degradation by neutrophil serine proteases.
Neutrophils store large quantities of neutrophil serine proteases (NSPs) that contribute, via multiple mechanisms, to antibacterial immune defences. Even though neutrophils are indispensable in fighting Staphylococcus aureus infections, the importance of NSPs in anti-staphylococcal defence is yet unknown. However, the fact that S. aureus produces three highly specific inhibitors for NSPs [the extracellular adherence proteins (EAPs) Eap, EapH1 and EapH2], suggests that these proteases are important for host defences against this bacterium. In this study we demonstrate that NSPs can inactivate secreted virulence factors of S. aureus and that EAP proteins function to prevent this degradation. Specifically, we find that a large group of S. aureus immune-evasion proteins is vulnerable to proteolytic inactivation by NSPs. In most cases, NSP cleavage leads to functional inactivation of virulence proteins. Interestingly, proteins with similar immune-escape functions appeared to have differential cleavage sensitivity towards NSPs. Using targeted mutagenesis and complementation analyses in S. aureus, we demonstrate that all EAP proteins can protect other virulence factors from NSP degradation in complex bacterial supernatants. These findings show that NSPs inactivate S. aureus virulence factors. Moreover, the protection by EAP proteins can explain why this antibacterial function of NSPs was masked in previous studies. Furthermore, our results indicate that therapeutic inactivation of EAP proteins can help to restore the natural host immune defences against S. aureus.


The role of early social play behaviors and language skills for shy children's later internalizing difficulties in school.
Research has demonstrated links from early childhood shyness to socioemotional problems later in life. This longitudinal study explored the role of early social play behaviors and language skills in the associations between childhood shyness and later internalizing and language difficulties in school. Participants were N = 7,447 children (50.1% girls) from the Norwegian Mother, Father, and Child Cohort Study (MoBa). Latent direct, indirect, and interaction path analyses were performed within a structural equation framework. Results showed that mother-rated childhood shyness from age 18 months to age five years was associated with mother-rated internalizing difficulties and language problems at age eight years. Lower levels of teacher-reported social play behaviors and poorer language skills in preschool increased the risk of later anxiety problems among shy children, whereas higher levels of language competencies and social play behaviors buffered against later anxiety problems. The study identifies some of the early risk and protective factors that may influence shy children's socio-emotional functioning and adjustment.


Gastrointestinal cancer metastasis and lymphogenous spread: viewpoint of animal models of lymphatic obstruction.
Primary gastrointestinal cancer frequently spreads to the mesentery, omentum and other parts of the peritoneum and these deposits are generally considered to be induced by intraperitoneal seeding from the primary lesion. In this work, we examined the spread of gastrointestinal cancer from the viewpoint of lymphogenous metastasis using a rat model of mesenteric lymph vessel obstruction. With these models, we carried out mesenteric lymphangiography on the fourth and sixth postoperative days (five animals each) to examine morphological changes in the lymph vessels and lymph flow. In model animals with mesenteric lymph vessel obstruction, re-celiotomy, performed on the fourth postoperative day, revealed marked mesenteric edema and enlargement of the mesenteric lymph nodes, suggestive of lymph retention. We also carried out mesenteric lymphangiography and obtained images of extensive mesenteric lymph vessels and reflux of lymph distal to the obstruction point in all five animals. On the sixth postoperative day, we obtained lymphangiographic images of lymphatico-venous communication in the mesentery in all five animals. Thus in animals with lymph vessel obstruction, the lymph flow appeared to change to lymphatico-venous communication or reverse lateral flow. In clinical cases, it is conceivable that lymph retention and reflux of lymph induced by lymph vessel obstruction sometimes play a role in the mechanism of intraperitoneal cancer dissemination and hematogenous metastasis.


Relationship between magnitude of applied torque in pre-swing phase and gait change for prevention of trip in elderly people.
Elderly people are at risk of tripping because of their narrow range of articular motion. To avoid tripping, gait training that improves their range of articular motion would be beneficial. In this study we propose a gait-training robot that applies a torque during the pre-swing phase to achieve this goal. We investigated the relationship between magnitude of applied torque and change in the range of knee-articular motion while walking before and after the application of this torque. We developed a wearable robot and carried out an experiment on human participants in which a motor pulls a string embedded on the robotic frame, applying torque in the pre-swing phase for a period of 20 [s]. Before and after applying torque the participant walked normally for 15 [s] without interference from the robot. We found that knee flexion angle increased after applying the torque if the torque was within the range of approximately 6-8 [Nm]. Therefore, we were able to verify that a new range of knee articular motion can be learned through application of torque.


Human Papillomavirus 16 E7 Stabilizes APOBEC3A Protein by Inhibiting Cullin 2-Dependent Protein Degradation.
APOBEC3 (A3) mutation signatures have been observed in a variety of human cancer genomes, including those of cervical and head and neck cancers caused by human papillomavirus (HPV) infection. However, the driving forces that promote off-target A3 activity remain mostly unclear. Here, we report a mechanism for the dramatic increase of A3A protein levels in HPV-positive keratinocytes. We show that expression of the viral protein E7 from high-risk HPVs, but not E7 from low-risk HPVs, significantly prolongs the cellular half-life of A3A protein in human keratinocytes and HPV-positive cancer cell lines. We have mapped several residues within the cullin 2 (CUL2) binding motif of HPV16 E7 as being important for mediating A3A protein stabilization. Furthermore, we provide direct evidence that both A3A and HPV16 E7 interact with CUL2, suggesting that the E7-CUL2 complex formed during HPV infection may regulate A3A protein levels in the cell. Using an in vitro cytidine deaminase assay, we show that E7-stabilized A3A remains catalytically active. Taken together, our findings suggest that the HPV oncoprotein E7 dysregulates endogenous A3A protein levels and thus provides novel mechanistic insight into cellular triggers of A3 mutations in HPV-positive cancers.IMPORTANCE Human papillomavirus (HPV) is causally associated with over 5% of all human malignancies. Several recent studies have shown that a subset of cancers, including HPV-positive head and neck and cervical cancers, have distinct mutational signatures potentially caused by members of the APOBEC3 cytidine deaminase family. However, the mechanism that induces APOBEC3 activity in cancer cells is poorly understood. Here, we report that the HPV oncoprotein E7 stabilizes the APOBEC3A (A3A) protein in human keratinocytes by inhibiting ubiquitin-dependent protein degradation in a cullin-dependent manner. Interestingly, the HPV E7-stabilized A3A protein maintains its deaminase activity. These findings provide a new insight into cancer mutagenesis enhanced by virus-induced A3A protein stabilization.


Cotrel-Dubousset instrumentation technique for revision of failed lumbosacral fusion.
Failed lumbosacral fusion represents a major problem for the orthopaedic surgeon. The authors report on a clinical study in which 18 patients, all previously operated on and still symptomatic, were revised using Cotrel Dubousset instrumentation to achieve rigid fixation and to correct deformities at the lumbosacral junction. In short-term follow-up, there have been no failures of hardware and the patients' clinical symptoms have improved. The surgical procedure is described, the biomechanical rationale of lumbosacral instability is analyzed, and a method of restoring physiologically normal frontal and saggital curvatures is offered.


Assessment of temporomandibular joint bone changes associated with anterior disc displacement: An MRI cross-sectional study.
This cross-sectional study aimed to evaluate the presence of bone changes on magnetic resonance imaging (MRI) scans of patients with temporomandibular joint (TMJ) anterior disc displacement (ADD) with reduction (ADDWR) and without reduction (ADDWoR). TMJ-MRI scans were screened for the presence of ADD. 285 scans presented ADD, being further divided into ADDWR (n = 188) and ADDWoR (n = 97). Bone changes on the mandibular condyle and articular eminence were also assessed and computed. The chi-square test compared the association of these bone changes with the presence of ADDWR and ADDWoR, with a significance level of 5 %. Also, the prevalence ratio (PR) was calculated. In the mandibular condyle, subchondral cyst (p = 0.035, PR = 1.08) and bone edema (p = 0.044, PR = 2.40), more prevalent on ADDWR, and generalized sclerosis (p = 0.015, PR = 1.04), more prevalent on ADDWoR, presented significant association with ADD. On the articular eminence, generalized sclerosis (p = 0.015, PR = 1.04) and articular surface flattening (p = 0.003, PR = 1.19) presented significant association with ADD, both more prevalent on ADDWoR. Bone changes are usual findings in TMJ with ADD diagnosis. The real influence of ADD is not fully clear, although clinicians should be aware of patients with this condition, to provide an early diagnosis and improve patient´s prognosis.


The muscle dystrophy-causing ΔK32 lamin A/C mutant does not impair the functions of the nucleoplasmic lamin-A/C-LAP2α complex in mice.
A-type lamins are components of the nuclear lamina, a filamentous network of the nuclear envelope in metazoans that supports nuclear architecture. In addition, lamin A/C can also be found in the interior of the nucleus. This nucleoplasmic lamin pool is soluble in physiological buffer, depends on the presence of the lamin-binding protein, lamina-associated polypeptide 2α (LAP2α) and regulates cell cycle progression in tissue progenitor cells. ΔK32 mutations in A-type lamins cause severe congenital muscle disease in humans and a muscle maturation defect in Lmna(ΔK32/ΔK32) knock-in mice. Mutant ΔK32 lamin A/C protein levels were reduced and all mutant lamin A/C was soluble and mislocalized to the nucleoplasm. To test the role of LAP2α in nucleoplasmic ΔK32 lamin A/C regulation and functions, we deleted LAP2α in Lmna(ΔK32/ΔK32) knock-in mice. In double mutant mice the Lmna(ΔK32/ΔK32)-linked muscle defect was unaffected. LAP2α interacted with mutant lamin A/C, but unlike wild-type lamin A/C, the intranuclear localization of ΔK32 lamin A/C was not affected by loss of LAP2α. In contrast, loss of LAP2α in Lmna(ΔK32/ΔK32) mice impaired the regulation of tissue progenitor cells as in lamin A/C wild-type animals. These data indicate that a LAP2α-independent assembly defect of ΔK32 lamin A/C is the predominant cause of the mouse pathology, whereas the LAP2α-linked functions of nucleoplasmic lamin A/C in the regulation of tissue progenitor cells are not affected in Lmna(ΔK32/ΔK32) mice.


[Effective inhibition of EB virus-encoded latent membrane protein-1 by siRNA in EB virus (+) nasopharyngeal carcinoma cell].
To evaluate the application of RNA interference in the study of latent membrane protein-1 (LMP-1) in EB virus-positive nasopharyngeal carcinoma (NPC) cell line C611. Observe the effects of LMP-1 silencing on NPC cell growth. Four synthesized small interference RNA (siRNA) were transfected into NPC cell using Oligofectamine reagent. LMP-1 mRNA level was determined by semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR). Flow cytometry and MTT assay were employed to analyze the effects on cell cycle and proliferation. The most effective sequence found out among the 4 candidates. Single dose of this siRNA caused nearly 90% loss of LMP-1 mRNA in C611 cell. The specific inhibition could last for 96 hours if re-transfection was preformed. LMP-1 siRNA treatment resulted in cell cycle arrest at G0-G1 stage in C611, accompany with a reduction of cell proliferation by 32.9%. While EBV-negative NPC cells appeared unaffected. These results provided solid testimony that EBV-encoded latent membrane protein-1 was vulnerable to RNA interference and, selective inhibition of LMP-1 had anti-proliferation effect on NPC cell. RNA interference could be a powerful tool in further investigations of LMP-1 and a novel therapeutic strategy for EBV-related NPC patients.


Modulation of the Gut Microbiota by Resistant Starch as a Treatment of Chronic Kidney Diseases: Evidence of Efficacy and Mechanistic Insights.
Chronic kidney disease (CKD) has been associated with changes in gut microbial ecology, or "dysbiosis," which may contribute to disease progression. Recent studies have focused on dietary approaches to favorably alter the composition of the gut microbial communities as a treatment method in CKD. Resistant starch (RS), a prebiotic that promotes proliferation of gut bacteria such as Bifidobacteria and Lactobacilli, increases the production of metabolites including short-chain fatty acids, which confer a number of health-promoting benefits. However, there is a lack of mechanistic insight into how these metabolites can positively influence renal health. Emerging evidence shows that microbiota-derived metabolites can regulate the incretin axis and mitigate inflammation via expansion of regulatory T cells. Studies from animal models and patients with CKD show that RS supplementation attenuates the concentrations of uremic retention solutes, including indoxyl sulfate and p-cresyl sulfate. Here, we present the current state of knowledge linking the microbiome to CKD, we explore the efficacy of RS in animal models of CKD and in humans with the condition, and we discuss how RS supplementation could be a promising dietary approach for slowing CKD progression.


Activation of protein kinase C mediates altered pulmonary vasoreactivity induced by tumor necrosis factor-alpha.
We postulated that tumor necrosis factor-alpha (TNF) "primes" the lung for the development of pulmonary vasoconstriction and edema by activating protein kinase C (PKC). Guinea pigs were injected with TNF (1.6 x 10(5) U/kg i.p.), and the lungs were isolated 4 h later. Compared with controls, TNF pretreatment resulted in greater increases in pulmonary vascular resistance and pressure and lung weight, in response to the thromboxane A2 mimetic, U-46619 (122 pmol/min). Treatment with TNF resulted in 1) pulmonary arterial endothelial PKC activation, 2) increased lung polymorphonuclear neutrophil (PMN) sequestration, 3) increased levels of superoxide radical (O2.) in lung effluent, and 4) decreased nitrite levels (NO2-, oxidation product of nitric oxide) in lung effluent. Intraperitoneal treatment with calphostin C (3 microM, 15 min prior to treatment with TNF) prevented the effects of TNF on 1) PKC activation, 2) the hemodynamic responses to U-46619, and 3) the levels of NO2- and O2(.). PKC activation does not mediate TNF-induced lung sequestration of PMN, since calphostin C had no effect on lung myeloperoxidase activity. The data suggest that PKC activation mediates TNF-induced 1) increases in O2., 2) decreases in NO2-, and 3) increases in vasoreactivity and edema in response to U-46619.


[Reoperation of hip endoprostheses].
Experiences gained in 106 reoperations of 88 patients following 1968 total and 18 Wagner arthroplasties, performed in the Department of the authors between 30. 05. 1969. and 30. 06. 1991., are described. They think that after the THR yearly control and radiological examinations are necessary. Radiological signs in symptomless patients do not mean operative indication, in these cases regular control is thought to be even more important. Big loss of bone with loosening makes reoperation in symptomless patients necessary as with the progression of bone destruction the danger of fracture increases and the possibility of reimplantation becomes dubious. In dubious cases bone scintigraphy may be of help. The technical solutions used by them are described. At the planning of reoperation the age of the patient, the state of the acetabulum and femur are considered. Under 60 years of age and at loosening with big bone loss cementless prosthesis and bone transplantation are suggested. The most important is thought to be to reach stable fixation. Attention is called that the performance of reoperation needs good technical skills.


Healthcare associated infective endocarditis: a distinct entity.
The terms hospital- and community-acquired infections do not cover any longer the full spectrum of acquisition of infection. Consequently, the term healthcare associated infection (HCA) has been recently introduced. In order to examine the applicability of 'HCA infection' to patients with infective endocarditis (IE), 125 episodes of culture-positive IE were categorized into 3 groups of acquisition. 14 (11%) of 125 episodes were defined as hospital acquired (HA) IE (onset of more than 72 h after admission), 52 (42%) as HCA (IE on admission in patients with significant previous healthcare contact), and 59 (47%) as community acquired (CA) (IE on admission in people without recent healthcare contact). 41 (77%) of the 53 causative agents in the HCA IE group were typical nosocomial pathogens, whereas these types of pathogens constituted only 22% (14/64) of the microorganisms in the group of CA IE (p<0.0001). Mortality in the HA and HCA groups combined was significantly higher than that in the CA group (19/62, 31%, vs 6/59, 10%, p=0.01). HCA IE should be recognized as a distinct category that constitutes a large proportion of all cases of IE. HCA IE is significantly different from CA IE and, therefore, may require a different therapeutic approach.


Efficacy and Initial Safety Profile of CXCL12 Treatment in a Rodent Model of Urinary Sphincter Deficiency.
Disappointing results of skeletal muscle precursor cell (skMPC) therapy for women with intrinsic urinary sphincter deficiency (ISD) associated urinary incontinence has increased interest in alternative sphincter regenerative approaches. This study was to measure the safety and efficacy of the cell homing chemokine CXCL12 versus skMPCs in a rat model of ISD. Thirty-six adult female Sprague Dawley rats were divided into 6 treatment (Tx) conditions: (a) no ISD/noTx [Control]; (b) ISD/noTx; (c) ISD + skMPCs; (d) ISD + 3.5 mg CXCL12; (e) ISD + 7mg CXCL12; and (f) ISD + 14 mg CXCL12. Tx's were injected directly into the sphincter complex 30 days post ISD and rats euthanized 30 days post Tx. Blood samples for measurements of kidney and liver function, white and red blood cell counts, were taken at baseline and at euthanasia. Leak point pressures (LPP) were measured prior to, and sphincter collagen/muscle content measured after, euthanasia. There were no effects of treatments on white or red/white blood cell counts, kidney/liver function tests or histopathology of the urinary sphincter complex or surrounding tissues. ISD lowered LPP 35% and sphincter muscle content by 17% versus control rats. CXCL12, but not skMPC injections, restored both LPP to control values in a dose-dependent fashion. Both skMPCs and CXCL12 restored sphincter muscle content to control values. This chemokine approach may represent a novel therapeutic option for ISD and appears, at least short-term, to produce little clinical or tissue pathology. Stem Cells Translational Medicine 2017;6:1740-1746.


A comparative study of the effects of nitric oxide and carbon monoxide on the in vivo release of gonadotropin-releasing hormone and neuropeptide Y from rat hypothalamus during the estradiol-induced luteinizing hormone surge: estimation by push-pull perfusion.
Recent evidence suggests that nitric oxide (NO), a free radical gas, plays an important role in regulating the function of a variety of neuroendocrine systems. With respect to the hypothalamo-pituitary-gonadal axis, a stimulatory effect of NO on the release of gonadotropin-releasing hormone (GnRH) from rat hypothalamus has been demonstrated in vitro. However, no previous study has reported NO-stimulated secretion of GnRH from in vivo hypothalamus, and also the precise cellular site of action of NO within the GnRH neuronal system remains to be elucidated. In the present study, utilizing the push-pull perfusion technique of rat hypothalamus, we examined the effect of L-arginine (L-Arg), an NO donor, on the release of GnRH, neuropeptide Y and cyclic GMP (c-GMP), which is a pivotal second messenger molecule of the NO system. For comparison, we also examined the effect of carbon monoxide (CO), another putative gaseous neurotransmitter, using hematin, a CO donor. During the period of 11.00-18.00 h, we collected blood and hypothalamic perfusates from ovariectomized adult rats that had been implanted with an estradiol capsule 2 days before. During the entire period of observation, L-Arg (1.0 or 10 mM), hematin (10 or 100 microM) or artificial cerebrospinal fluid alone (as the control) was infused into the medial preoptic area (MPOA) where there are cell bodies of GnRH neurons, or the median eminence-arcuate nucleus complex (ME-ARC) where axon terminals of GnRH neurons are localized. Although 10 mM of L-Arg significantly stimulated GnRH and c-GMP, but not neuropeptide Y, levels in both the MPOA and ME-ARC, GnRH and c-GMP in the ME-ARC were already increased by 1.0 mM of L-Arg. By contrast, both concentrations of hematin were without effect at either site of the hypothalamus. This study is the first to demonstrate that NO is capable of stimulating GnRH release from rat hypothalamus in vivo. Our data also suggests that both cell bodies and axon terminals of GnRH neurons may be sites of action of NO. Our data do not support a previous study by other investigators that reported a stimulatory effect of CO on the GnRH release.


Insights into early pig domestication provided by ancient DNA analysis.
Pigs (Sus scrofa) were first domesticated between 8,500 and 8,000 cal BC in the Near East, from where they were subsequently brought into Europe by agriculturalists. Soon after the arrival of the first domestic pigs in northern Europe (~4500 BC), farmers are thought to have started to incorporate local wild boars into their swine herds. This husbandry strategy ultimately resulted in the domestication of European wild boars. Here, we set out to provide a more precise geographic and temporal framework of the early management of suid populations in northern Europe, drawing upon mitochondrial DNA haplotype data from 116 Neolithic Sus specimens. We developed a quantitative mathematical model tracing the haplotypes of the domestic pigs back to their most likely geographic origin. Our modelling results suggest that, between 5000 and 4000 BC, almost all matrilines in the north originated from domesticated animals from the south of central Europe. In the following period (4000-3000 BC), an estimated 78-100% of domesticates in the north were of northern matrilineal origin, largely from local wild boars. These findings point towards a dramatic change in suid management strategies taking place throughout south-central and northern Europe after 4000 BC.


Mechanisms of motility changes during acute intestinal obstruction in the dog.
We investigated the effects of autonomic drugs and the role of intestinal contents on the motility changes that occur during acute obstruction. Myoelectric activity was recorded from seven electrodes spaced at 3-cm intervals along the midjejunum of nine conscious dogs. Another animal had electrodes evenly placed throughout the small bowel. Obstruction was created by inflation of an intraluminal balloon. Systemic arterial blood pressure and pulse rate were monitored. Initially, motor activity of the small intestine increased proximal to an acute intestinal obstruction and decreased distally. Recordings from the entire small intestine revealed that these effects occurred almost immediately in the region of the obstruction but not at more distant sites. Within 2-3 h, however, proximal hypermotility had extended to the duodenum and distal inhibition had progressed to the terminal ileum. Diversion of intestinal contents without obstruction reduced myoelectric activity distal to the site of drainage. However, reinfusion of chyme distal to the site of obstruction failed to restore inhibited motor activity to control levels. Atropine sulfate (50 micrograms/kg) decreased and neostigmine (5 micrograms X kg-1 X min-1) potentiated the hyperactivity proximal to the obstruction, but neither agent significantly affected the distal inhibition. Phentolamine (1 mg/kg) and propranolol (1 mg/kg) had no effect on proximal or distal motor activity during obstruction; these were doses that blocked cardiovascular responses to adrenergic agonists. These results suggest that changes in luminal contents and in nervous activity both contribute to the intestinal motility changes that accompany obstruction.(ABSTRACT TRUNCATED AT 250 WORDS)


NUCB2 polymorphisms are associated with an increased risk for type 2 diabetes in the Chinese population.
The nucleobindin 2 (NUCB2) gene encodes the NUCB2 protein, which plays a critical role in glucose metabolism and diabetes. This study explored the correlation between NUCB2 genetic variants and type 2 diabetes mellitus (T2DM). The study further examined the different NUCB2 variants that confer risk to T2DM in Chinese Han populations. This study evaluated the anthropometric and glycemic profiles of 578 T2DM patients and 1,609 healthy controls. Subsequently, we genotyped five single nucleotide polymorphisms (SNPs) (rs10832756, rs1330, rs10766383, rs10832757, and rs11024251) in all the study participants using a Sequenom Mass ARRAY SNP genotyping platform. The distribution of polymorphisms was significantly different between the T2DM patients and healthy controls. Our logistic regression analysis results showed that the five NUCB2 SNPs are significantly correlated with the risk for T2DM, especially rs11024251(P=2.97×10-6). Interestingly, analysis of male and female sub-populations separately showed that only two of the SNPs (rs10832757 and rs11024251) have significant correlation to T2DM in males [P=0.0244, odds ratio (OR) 1.28 and P=0.0062, OR 1.35, respectively). In females however, we identified four significant SNPs (rs1330, rs10766383, rs10832757, and rs11024251; P<0.05, OR 1.31-1.42). Furthermore, we found that rs1330 is associated with body mass index of female subpopulation only (P=0.0174, β =0.0060). NUCB2 polymorphisms could have a pivotal role in the presence of T2DM. Sex-specific SNPs of NUCB2 could account for the differences in clinical features of T2DM between male and female subpopulations. Nevertheless, our results should be replicated using larger sample sizes, and experimental investigations are needed to elucidate the molecular mechanisms of the associations observed in this study.


Prevalence and associated factors of diabetic retinopathy in Chandrubeksa Hospital, Directorate of Medical Services, Royal Thai Air Force.
To evaluate the prevalence and associated factors of diabetic retinopathy (DR) in patients with type 2 diabetes in the diabetes clinic at Chandrubeksa Hospital. A cross-sectional study was performed on 261 type 2 diabetic patients at Chandrubeksa Hospital on January 2011. They all underwent fundus examination by ophthalmologists using indirect ophthalmoscope to check for any signs of DR. Retinopathy was presented in 67 (25.70%) patients who were categorized into non-proliferative and proliferative types, 23.4% and 2.3% respectively. The patients who received insulin treatment were more likely to have DR than those who had not (OR 3.95, 95% CI 1.86, 8.39). Those who had had diabetes for more than 5 years were more likely to have diabetic retinopathy than those with diabetes for a lesser amount of time (OR 2.36, 95% CI 1.28, 4.33). Insulin treatment and the duration of diabetes are the significant associated factors for developing diabetic retinopathy in type 2 diabetic patients. The authors emphasize the necessity of regular eye check-ups which can provide the patients with early detection so that treatment can begin before much damage occurs.


Genetic predisposition to cancer.
A minor fraction of cancer occurs in persons who have strong dominantly transmissible genetic predisposition. Retinoblastoma and Wilms' tumor are the most thoroughly studied examples. Hereditary cases involve mutations at the same chromosomal sites. In most carriers of mutation the change cannot be visualized; in some, it is a visible deletion. A significant fraction of nonhereditary cases involve deletion at the same site in tumor cells only, suggesting that mutation at this site is necessary for the initiation of tumor, whether hereditary or not. This may be a general model for human cancer. The initiating mutation is not sufficient, however, since only rare cells are transformed. A second event may be genetic, such that recessive loss of the gene occurs. A two-event genetic model for a major fraction of human cancers is also compatible with the well-established, age-specific incidence of various cancers.


Five-year results of radial keratotomy in the myopia over 6 diopters.
A number of studies have documented the reasonable efficacy and safety of radial keratotomy, but most based upon results obtained in low or moderate myopia or short term follow up after surgery. We complied 5 year and longer follow up data on 91 consecutive radial keratotomy surgeries on high myopia (over -6.00 diopters) performed by one surgeon 5 year-follow up was obtained on 21 (23%) of these eyes. The mean spherical equivalent before surgery was -11.02 diopters (D), the average keratometry value was 44.40 D, and all of the eyes had an uncorrected visual acuity of 0.04 or less. The average change in spherical equivalent was 3.44 D for eyes examined at 1 year, compared with 3.05 D for eyes at 3 years and 2.87 D at 5 years after surgery. Average keratometry value were 42.30 D at 1 year, 41.60 D at 3 years, and 41.30 D at 5 years after surgery. In our study, the decrease in spherical equivalent of 0.57 D was statistically significant (P < 0.05), as was the reduction in average keratometry value of 1.00 D. The effect of the surgery on spherical equivalent continued to regress through all the 5 years of follow up. However, the keratometric measurement decreased up to 5 years which indicated progressive flattening of the cornea. Also we divided these eyes into 2 groups, lower-myopic group (-6.00 D-(-)9.75 D) and higher-myopic group (over -10.00 D). In each category, the changes in spherical equivalent were 3.60 D, 2.21 D at 5 years, compared with 3.65 D, 3.25 D at 1 year respectively.(ABSTRACT TRUNCATED AT 250 WORDS)


Ultraflex stent--benefits and risks in ultimate palliation of advanced, malignant stenosis in the esophagus.
Sophisticated endoscopical palliation in end-stage malignant stenosis of the esophagus and gastroesophageal-junction must be weighed against associated morbidity and mortality. In a prospective study we investigated benefits and risks of one type of coated, self-expandable stent in ultimate palliation of esophageal neoplasms focusing on factors that might predispose patients to develop complications. 33 men (70.2%) and 14 women (29.8%), (mean age 68.3 years, range from 38 to 90 years), suffering from nonresectable malignant stenosis of the esophagus due to advanced tumor stage and/or functional inoperability were treated by using a covered, self-expandable stent (covered ULTRAFLEX esophageal stent system, Microinvasive, Boston Scientific Corporation, Boston, MA). Stenting was indicated because of severe dysphagia for liquids and saliva in 41 (87.2%) patients, tracheoesophageal fistula in 5 (10.6%) patients and in one case of tumor bleeding (2.1%). 32 out of 47 patients had had one or other multiple treatment modalities before stenting. In 15 patients stenting was the first and only therapeutic option. All patients experienced an improvement of dysphagia immediately after stenting. Eight out of 47 patients (17.1%) developed major stent-associated complications: Early complications within 4 days after implantation evolved in two cases, with one patient dying from stent-induced perforation with consecutive mediastinitis and multi-organ failure. Late complications (20 to 180 days after stent implantation) occurred in 6 cases: Three esophagotracheal fistulae (two with tracheal compression) induced by stent expansion, one stent-induced bleeding and two stent dislocations. After appropriate complication management all but two patients were able to be discharged after a mean of 2.6 days. Multivariate analysis did not show any factors that might have predicted the development of major stent-associated complications. Implantation of the self-expandable Ultraflex-stent will efficiently palliate dysphagia, bleeding and fistulae. The 17% risk of major complications seems acceptable regarding the inherent problems of alternative treatment options, like gastrostomy, PEG, nasogastric tube or long-term parenteral feeding.


Chronic osteitic rhinosinusitis as a manifestation of cystic fibrosis: A case report.
A 28-year-old male patient with a history of cystic fibrosis (CF) was referred to the University of Connecticut School of Dental Medicine for an evaluation of a cystic lesion in the right maxilla using cone-beam computed tomography (CBCT). CF is an autosomal recessive disease characterized by an abnormal production of viscous mucus, affecting the mucociliary clearance. The CBCT scan revealed a large cystic lesion in the right maxilla extending from the right maxillary second molar to the midline in the region of the right central incisor with a significant buccal expansion. Further evaluation revealed complete opacification of the paranasal sinuses with medial bulging of the lateral maxillary sinus walls. The maxillary and sphenoid sinuses also appeared hypoplastic. The peculiar finding seen in this case was the presence of marked sclerosis and an increase in the thickness of the adjacent bony framework. This report aimed to describe the common sinonasal findings associated with CF and its underlying pathophysiology.


Validation of the German version of two scales (RIS, RCS-HCP) for measuring regret associated with providing healthcare.
The regret intensity scale (RIS) and the regret coping scale for healthcare professionals (RCS-HCP) working in hospitals assess the experience of care-related regrets and how healthcare professional deal with these negative events. The aim of this study was to validate a German version of the RIS and the RCS-HCP. The RIS and RCS-HCP in German were first translated into German (forward- and backward translations) and then pretested with 16 German-speaking healthcare professionals. Finally, two surveys (test and 1-month retest) administered the scales to a large sample of healthcare professionals from two different hospitals. Of the 2142 eligible healthcare professionals, 494 (23.1%) individuals (108 physicians) completed the cross-sectional web based survey and 244 completed the retest questionnaire. Participants (n = 165, 33.4% of the total sample) who reported not having experienced a regret in the last 5 years, had significantly more days of sick leave during the last 6 months. These participants were excluded from the subsequent analyses. The structure of the scales was similar to the French version with a single dimension for the regret intensity scale (Cronbach's alpha: 0.88) and three types of coping strategies for the regret coping scale (alphas: 0.69 for problem-focused strategies, 0.67 for adaptive strategies and 0.86 for the maladaptive strategies). Construct validity was good and reproduced the findings of the French study, namely that higher regret intensity was associated with situations that entailed more consequences for the patients. Furthermore, higher regret intensity and more frequent use of maladaptive strategies were associated with more sleep difficulties and less work satisfaction. The German RIS and RCS-HCP scales were found valid for measuring regret intensity and regret coping in a population of healthcare professionals working in a hospital. Reporting no regret, which corresponds to the coping strategy of suppression, seems to be a maladaptive strategy because it was associated with more frequent sick day leaves.


Comparison between bupivacaine injection and mini-tenotomy in the management of horizontal small angle strabismus in children.
To compare the outcome of bupivacaine (BUP) injection vs mini-tenotomy of extra-ocular muscles in treating small angle horizontal strabismus in children. A prospective comparative study that included a total of 40 patients. Twenty patients received 3 ml of 0.75% Bupivacaine (BUP) injection in both medial recti in case of exotropia and in both lateral recti in case of esotropia. MRI orbit was performed before and 30-60 days' post injection of bupivacaine to estimate changes in muscle size. Mini-tenotomy was done in the other 20 patients, performed on both lateral recti in case of exotropia and on both medial recti in case of esotropia. Mean change of alignment at the end of 6 months in exotropic patients in bupivacaine group was 5.50 ± 4.10 PD and in esotropia patients 4.00 ± 3.38 PD with an average increase in muscle thickness of 0.12 mm ± 0.08 and 0.13 mm ± 0.09 in exotropia and esotropia, respectively. There was an average increase in volume 23 mm3 ± 17.3 and 17.00 mm3 ± 9.50 in exotropia and esotropia, respectively, as measured with MRI. The mean change of alignment in mini-tenotomy was 5.33 ± 4.12 PD, 5.75 ± 4.95 PD in exotropia and esotropia, respectively. Bupivacaine and mini-tenotomy are safe and effective alternative treatment, that improved eye alignment in 65% of patients with small angle horizontal deviation.


Viral gametocytic hypertrophy caused by a papova-like virus infection in the Pacific oyster Crassostrea gigas in Korea.
During a routine survey of the Pacific oyster Crassostrea gigas in Tongyoung (previously Chungmu) on the southern coast of Korea, basophilic inclusions were observed in the gonadal tissues. They were detected from March to May at a prevalence rate of 3.3 to 7.1%. The inclusion bodies were Feulgen-positive and stained orange-red with phloxine tartrazine. Electron microscopic observation revealed non-enveloped, icosahedral particles 40 to 45 nm in diameter. These morphological characteristics resemble those of papova virus-like inclusions previously described from Pacific and eastern (American) oysters C. virginica in North America. Although many mitochondrial bodies and intact sperm cells were observed around the inclusion body, no host reaction, such as hemocytic infiltration, was detected.


Paclitaxel, carboplatin, 5-fluorouracil, and radiation for locally advanced esophageal cancer: phase II results of preliminary pharmacologic and molecular efforts to mitigate toxicity and predict outcomes: North Central Cancer Treatment Group (N0044).
Locally advanced esophageal cancer is challenging to treat. This study tested a 3-drug, multimodality approach. Chemotherapy dose reductions, the addition of amifostine, and pharmacogenetics were tested in an effort to mitigate toxicity and predict outcomes. This phase II trial tested chemotherapy (carboplatin area under the curve = 4 [lower dose than that from Meluch et al] on day 1 and 22, 5-fluorouracil 225 mg/m2 per day continuous infusion on days 1 to 42, and paclitaxel 200 mg/m2 on days 1 and 22) with concomitant radiation 4500 cG for locally advanced esophageal cancer. Esophagectomy was scheduled after radiation. Amifostine 500 mg subcutaneously before radiation was given to the first 19 patients. Among 54 eligible patients, the pathologic complete response rate was 35% (95% confidence interval [CI], 23%-49%). Median survival was 21.2 months (95% CI, 13.6-37.6 months), and median time to cancer recurrence/progression 19 months (95% CI, 11.4-44.6 months). Nearly all patients (94%) suffered at least one grade 3 or worse adverse event, including 3 treatment-related deaths. Amifostine was discontinued because of one of these deaths. There was no statistically significant difference in the rates of severe adverse events among patients who received amifostine and those who did not. Genotyping for polymorphisms of dihydropyrimidine dehydrogenase, cytochrome P3A4, and glutathione-S-transferase did not predict tumor response or severe adverse events. This 3-drug, multimodality approach yielded a pathologic complete response rate of 35%, but the severe adverse event rate was high. Utilizing amifostine to reduce toxicity or employing molecular approaches to predict outcomes did not show promise.


Association Between Muscle Strength and Cystatin C-Based Estimated Glomerular Filtration Rate Among Middle-Aged and Elderly Population: Findings Based on the China Health and Retirement Longitudinal Study (CHARLS), 2015.
Patients with chronic kidney disease (CKD) are prone to muscle strength degeneration. However, the relationship between mild-to-moderate renal insufficiency and low muscle strength remains unclear. As cystatin C is not subject to muscular conditions and is a sensitive serum marker in preclinical renal disease, we aimed to investigate the association between estimated glomerular filtration rate (eGFR) based on cystatin C and muscle strength in the Chinese population. This was a cross-sectional study enrolling 12,398 Chinese participants aged above 45 years (5762 men and 6636 women) from the 2015 China Health and Retirement Longitudinal Study. Handgrip strength (HGS) was used to assess muscle strength. Locally weighted scatterplot smoothing (LOWESS) curves were employed to visualize the relationships between eGFR and HGS. Multivariable logistic regression was conducted to analyze the correlation between kidney function and low muscle strength. Significant differences in HGS by CKD stage were observed in both sexes after adjusting for age and body mass index. LOWESS curves demonstrated concomitant decreases in HGS and kidney function at eGFR levels below 120 mL/min/1.73 m2 in both sexes. According to multivariate logistic regression, participants with CKD stages 2 (odds ratio [OR]: 1.256, 95% confidence interval [CI]: 1.120-1.409), 3 (OR: 2.725, 95% CI: 2.2585-3.288), and 4-5 (OR: 3.069, 95% CI 1.747-5.392) had higher risk of low muscle strength than those who were normal or had CKD stage 1 after adjusting for demographic and clinical variables. Our study illustrated that CKD stage was independently associated with low muscle strength in Chinese middle-aged and elderly populations.


Lifestyle Implications of Home Mechanical Insufflation-Exsufflation for Children With Neuromuscular Disease and Their Families.
Mechanical insufflation-exsufflation (MI-E) is increasingly used in the home management of children with neuromuscular disease. Research to date has focused on the effect of MI-E on physical health. The aim of this study was to qualitatively investigate the impact of home MI-E on the child and family's lifestyle. Eight parents and 3 children participated in semistructured interviews. Five themes emerged from parent interviews demonstrating: (1) lifestyle implications, (2) parents becoming experts, (3) parents developing a sense of control over their child's condition, (4) an element of extra care, and (5) impacts on the parent-child relationship. Developing themes from the child interviews showed them adjusting to and then relying on the device. Home MI-E medicalized the home, but the overall lifestyle impact was positive. Although involving a small number of subjects, this study demonstrated a mixture of opposing impacts of home MI-E on lifestyle, both enabling and disabling, which need to be considered when introducing home MI-E. The positive impacts included greater ability to manage the child's health, including avoidance of hospital admissions. Negative impacts were greatest for those parents who were sole operators of the device, including a frequently disrupted lifestyle.


Self-emulsifying drug delivery systems (SEDDS): How organic solvent release governs the fate of their cargo.
Organic solvents are commonly used in self-emulsifying drug delivery systems (SEDDS) to increase payloads of orally administered poorly soluble drugs. Since such solvents are released to a varying extent after emulsification, depending on their hydrophilic nature, they have a substantial impact on the cargo. To investigate this impact in detail, quercetin and curcumin as model drugs were incorporated in SEDDS comprising organic solvents (SEDDS-solvent) of logP < 2 and > 2. SEDDS were characterized regarding size, payload, emulsification time and solvent release. The effect of solvent release on the solubility of these drugs was determined. Preconcentrates of SEDDS-solventlogP < 2 emulsified more rapidly (< 1.5 min) forming smaller droplets than SEDDS-solventlogP > 2. Although, SEDDS-solventlogP < 2 preconcentrates provided higher quercetin solubility than the latter, a more pronounced solvent release caused a more rapid quercetin precipitation after emulsification (1.5 versus 4 h). In contrast, the more lipophilic curcumin was not affected by solvent release at all. Particularly, SEDDS-solventlogP < 2 preconcentrates provided high drug payloads without showing precipitation after emulsification. According to these results, the fate of moderate lipophilic drugs such as quercetin is governed by the release of solvent, whereas more lipophilic drugs such as curcumin remain inside the oily phase of SEDDS even when the solvent is released.


What remains how. Archaeological and experimental charcoal features from cremation burials in the Rhineland.
This study investigates Roman-dated cremation relicts, i.e., charcoals as remnants of the pyre burning process and their potential for interpretation. Results are reported for analyses executed by the author at the Laboratory of Archaeobotany of the Institute of Prehistory at the University of Cologne within the longtime project "Archaeobotany in North-Rhine Westphalia". The study area comprises sites mainly in the Lower Rhine Bay (Niederrheinische Bucht). In total, 21 different wood types could be identified from charcoals from 278 burial cremations, typically with beech (Fagus) and oak (Quercus) occurring at highest frequencies. However, most wood types occur in very low frequencies. Few of the rarely occurring wood types, e.g. fir (Abies), hornbeam (Carpinus), maple (Acer), belong to primary grave goods. Some of the excavated charcoal features confirm ancient written and illustrated sources reporting cremation types (bustum, ustrina) and pyre construction. A comparison of archaeologically and experimentally gained charcoal amounts of bustum burials point to pyre sizes.


[Computed tomography of the pleura].
The paper examines CT images of the pleura and interlobar culci in health and in disease. For this, 403 patients were examined (420 CT studies), of whom 218 had pleural lesion and 185 formed a control group. The complex of studies involved computed tomography (CT) as compared with conventional radiation studies. The CT symptomatology of free and sacculated exudates, empyemas of the pleura, pleural depositions and adhesions, tumor lesions of the pleura. Based on the findings, an original scheme of free and sacculated pleural exudates was offered in CT images. The findings have led the authors to the conclusion that computed tomography is a more sensitive method in the evaluation of the pleura than standard X-ray study.


Microhardness and Penetration of Artificial White Spot Lesions Treated with Resin or Colloidal Silica Infiltration.
Infiltration of early enamel lesions by materials having remineralizing capacity seems to improve aesthetics and arrests caries progression. To evaluate and compare the surface microhardness and penetration depth of a low viscosity resin and colloidal silica nanoparticle infiltrates into artificially created white spot lesions. Forty extracted human central incisors were embedded in acrylic resin blocks exposing the labial surfaces of the crowns. The specimens were immersed in demineralizing solution for 96 hours to create white spot lesions on labial surfaces. The samples were then divided into two groups (n=20 each), where in Group 1-resin infiltration (ICON DMG, Hamburg, Germany) and Group 2-colloidal silica infiltration (Arrow Fine chemicals, Rajkot, Gujarat, India) was done. Samples were subjected to vicker's microhardness testing at baseline, after demineralization and after treatment with resin or colloidal silica infiltrates. Then, the crowns were sectioned longitudinally and penetration depth of the infiltrants was measured using confocal laser scanning microscope and compared the readings to lesion depth. All the collected data was subjected to statistical analysis using t-test. Resin infiltration group showed significantly greater increase in microhardness compared to colloidal silica infiltration (p=0.001). The percentage of penetration of the resin group was 67.14% and that of colloidal silica group was 54.53% indicating significant difference between the two. Resin infiltrates performed better in regaining the baseline microhardness and penetrating deep into the porous white spot lesions, when compared to colloidal silica infiltrates.


Reliability and Validity of the Korean Version of the Cancer Stigma Scale.
In this study the reliability and validity of the Korean version of the Cancer Stigma Scale (KCSS) was evaluated. The KCSS was formed through translation and modification of Cataldo Lung Cancer Stigma Scale. The KCSS, Psychological Symptom Inventory (PSI), and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 (EORTC QLQ-C30) were administered to 247 men and women diagnosed with one of the five major cancers. Construct validity, item convergent and discriminant validity, concurrent validity, known-group validity, and internal consistency reliability of the KCSS were evaluated. Exploratory factor analysis supported the construct validity with a six-factor solution; that explained 65.7% of the total variance. The six-factor model was validated by confirmatory factor analysis (Q (χ²/df)= 2.28, GFI=.84, AGFI=.81, NFI=.80, TLI=.86, RMR=.03, and RMSEA=.07). Concurrent validity was demonstrated with the QLQ-C30 (global: r=-.44; functional: r=-.19; symptom: r=.42). The KCSS had known-group validity. Cronbach's alpha coefficient for the 24 items was .89. The results of this study suggest that the 24-item KCSS has relatively acceptable reliability and validity and can be used in clinical research to assess cancer stigma and its impacts on health-related quality of life in Korean cancer patients.


'Common sense and a thick hide'. Physicians providing care to their own family members.
To determine how frequently physicians treat their relatives in 17 categories of care, their reasons for deciding to treat, and their level of comfort with this practice. Mailed survey. Rural, suburban, and urban practices in Oregon. Two thousand fourteen physicians in the following specialties: general practice, family practice, general internal medicine, general surgery, orthopedic surgery, obstetrics/gynecology, and pediatric medicine. One thousand two hundred ninety-two questionnaires (64%) were returned. Minor prescribing was done most frequently, followed by routine pediatric care, physical examinations, and minor surgery. All other forms of care occurred rarely, and there appears to be a gradient based on the level of complexity, seriousness, and potential for conflict with privacy. In general, older, male, and rural physicians provided more services to family members than their younger, female, and urban counterparts. General and family practitioners performed the most family care; general internists, the least. The most important reasons for providing care were convenience for the patient and request from relatives. Providers were most comfortable providing care to their children and least comfortable providing care to their grandparents. There is a wide range of practice, depending on the nature of the care and provider characteristics. Physicians report treating their own family members rarely and face significant dilemmas when doing so.


The accuracy of references in manuscripts submitted for publication.
To analyze the errors present in references cited in papers submitted for peer review for possible publication. Nineteen consecutive manuscripts submitted for peer review were assessed. They contained a total of 261 references. Manuscripts were submitted to 1 of 5 major radiology journals. Journal references were compared with either the original articles or abstracts obtained through MEDLINE. Book references were checked against the original book. In total, 259 of 261 references were obtained. The remaining 2 references were both out-of-print books that were not available. Each reference was checked and errors were identified as either major or minor, depending on the gravity of the error. Errors were analyzed to see whether they could be attributed to not adhering to journal guidelines or to other reasons. Of a total of 259 references, 56% (n = 145) contained at least 1 error, 53% (n = 137) contained minor errors and 15% (n = 39) contained major errors. Five per cent (n = 13) of references had more than 3 errors, and 79% (n = 274) of all errors were the direct result of authors not following journal instructions. Over half of all references included in manuscripts submitted to radiology journals contain at least 1 error. The majority are avoidable, resulting from failure to follow the journal's instructions to authors.


Cluster Size and Quinary Structure Determine the Rheological Effects of Antibody Self-Association at High Concentrations.
The question of how nonspecific reversible intermolecular protein interactions affect solution rheology at high concentrations is fundamentally rooted in the translation of nanometer-scale interactions into macroscopic properties. Well-defined solutions of purified monoclonal antibodies (mAbs) provide a useful system with which to investigate the manifold intricacies of weak protein interactions at high concentrations. Recently, characterization of self-associating IgG1 antibody (mAb2) solutions has established the direct role of protein clusters on concentrated mAb rheology. Expanding on our earlier work with three additional mAbs (mAb1, mAb3, and mAb4), the observed concentration-dependent static light scattering and rheological data present a substantially more complex relationship between protein interactions and solution viscosity at high concentrations. The four mAb systems exhibited divergent correlations between cluster formation (size) and concentrated solution viscosities dependent on mAb primary sequence and solution conditions. To address this challenge, well-established features of colloidal cluster phenomena could be applied as a framework for interpreting our observations. The initial stages of mAb cluster formation were investigated with small-angle X-ray scattering (SAXS) and ensemble-optimized fit methods, to uncover shifts in the dimer structure populations which are produced by changes in mAb interaction modes and association valence under the different solution conditions. Analysis of mAb average cluster number and effective hydrodynamic radii at high concentrations revealed cluster architectures can have a wide range of fractal dimensions. Collectively, the static light scattering, SAXS, and rheological characterization demonstrate that nonspecific and anisotropic attractive intermolecular interactions produce antibody clusters with different quinary structures to regulate the rheological properties of concentrated mAb solutions.


Surgical palliation for pancreatic cancer: will biliary bypass alone suffice?
Because a number of options are available to relieve the obstructed bile duct, stomach or both in patients with irresectable carcinoma of the pancreatic head, palliative surgery for this condition was reviewed retrospectively between 1971 and 1981 at the Royal United Hospital, Bath. One hundred and sixty-five patients underwent a biliary bypass procedure with (n = 37), or without (n = 128) gastric drainage. Thirty patients had a prophylactic gastroenterostomy to avoid gastric outlet obstruction: tumour encroachment made gastroenterostomy essential in seven others. After biliary bypass alone, operative mortality was 14%. After a concomitant gastroenterostomy, mortality was 27% (P less than 0.04). Within a year of biliary bypass alone, there was a 9% incidence of gastric outlet obstruction requiring gastric drainage, with an associated mortality rate of 18%. Survival after biliary bypass or biliary bypass with gastroenterostomy was equal (7-8 months). Except where gastric outlet obstruction is imminent, palliation for irresectable pancreatic head carcinomas should be by biliary bypass alone, because the addition of a gastroenterostomy almost doubles the mortality without any advantage in survival time.


Thermal Infrared Pedestrian Segmentation Based on Conditional GAN.
A novel thermal infrared pedestrian segmentation algorithm based on conditional generative adversarial network (IPS-cGAN) is proposed for intelligent vehicular applications. The convolution backbone architecture of the generator is based on the improved U-Net with residual blocks for well utilizing regional semantic information. Moreover, cross entropy loss for segmentation is introduced as the condition for the generator. SandwichNet, a novel convolutional network with symmetrical input, is proposed as the discriminator for real-fake segmented images. Based on the c-GAN framework, good segmentation performance could be achieved for thermal infrared pedestrians. Compared to some supervised and unsupervised segmentation algorithms, the proposed algorithm achieves higher accuracy with better robustness, especially for complex scenes.


'The Biggest Problem With Access': Provider Reports of the Effects of Wisconsin 2011 Act 217 Medication Abortion Legislation.
Abortion legislation in the United States determines people's access to services, including the abortion modality of their choice. In 2012, Wisconsin legislators passed Act 217, banning telemedicine for medication abortion and requiring the same physician to be physically present when patients signed state-mandated abortion consent forms and to administer abortion medications over 24 hours later. No research documented real-time outcomes of 2011 Act 217 in Wisconsin; this study documents providers' descriptions of the effects of Wisconsin abortion regulations on providers, patients, and abortion care in the state. We interviewed 22 Wisconsin abortion care providers (18 physicians and 4 staff members) about how Act 217 affected abortion provision. We coded transcripts using a combined deductive and inductive approach, then identified themes about how this legislation affects patients and providers. Providers interviewed universally reported that Act 217 negatively affected abortion care, with the same-physician requirement especially increasing risk to patients and demoralizing providers. Interviewees emphasized the lack of medical need for this legislation and explained that Act 217 and the previously enacted 24-hour waiting period worked synergistically to decrease access to medication abortion, disproportionately affecting rural and low-income Wisconsinites. Finally, providers felt Wisconsin's legislative ban on telemedicine medication abortion should be lifted. Wisconsin abortion providers interviewed underscored how Act 217, alongside previous regulations, limited medication abortion access in the state. This evidence helps build a case for the harmful effects of non-evidence-based abortion restrictions, which is crucial considering recent deferral to state law after the fall of Roe v Wade in 2022.


NKG2H-Expressing T Cells Negatively Regulate Immune Responses.
The biology and function of NKG2H receptor, unlike the better characterized members of the NKG2 family NKG2A, NKG2C, and NKG2D, remains largely unclear. Here, we show that NKG2H is able to associate with the signaling adapter molecules DAP12 and DAP10 suggesting that this receptor can signal for cell activation. Using a recently described NKG2H-specific monoclonal antibody (mAb), we have characterized the expression and function of lymphocytes that express this receptor. NKG2H is expressed at the cell surface of a small percentage of peripheral blood mononuclear cell (PBMC) and is found more frequently on T cells, rather than NK cells. Moreover, although NKG2H is likely to trigger activation, co-cross-linking of this receptor with an NKG2H-specific mAb led to decreased T cell activation and proliferation in polyclonal PBMC cultures stimulated by anti-CD3 mAbs. This negative regulatory activity was seen only after cross-linking with NKG2H, but not NKG2A- or NKG2C-specific monoclonal antibodies. The mechanism underlying this negative effect is as yet unclear, but did not depend on the release of soluble factors or recognition of MHC class I molecules. These observations raise the intriguing possibility that NKG2H may be a novel marker for T cells able to negatively regulate T cell responses.


Radiometric ear index test as a measure of delayed-type-hypersensitivity in the rat.
Intradermal skin tests performed in the pinna of the rat ear appeared to be 100 times more sensitive than classical flank skin tests in measuring Arthus and delayed-type hypersensitivity (DTH) reactions. One of these tests was antigen-induced thickening of the pinna of the ear. It was found to be a sensitive measure of Arthus reactivity at 4 h after irritation with antigen in both actively immunized rats and recipients of precipitating immune serum. The other test, radiometric ear index determination, exploits the fact that monocytes and monocyte derived macrophages accumulate at DTH reaction sites. The test was performed by labelling the precursors of these cells with a pulse of [3H]-thymidine and by determining radioactivity in biopsy specimens taken from test sites in the pinna of the ear. At a certain antigen dose range this objective and highly sensitive method was shown to measure a purely cell mediated reaction which could be transferred to normal recipients with thoracic duct lymphocytes but not with immune serum. It also behaved as a typical DTH reacttion in response to desensitizing injections of the specific antigen. Testing with unnecessarily high antigen doses, however, should be avoided since the strong early inflammation induced by them may interfere with the determination of DTH while using this sensitive assay.


A Modified Two-Way Active Avoidance Test for Combined Contextual and Auditory Instrumental Conditioning.
Available two-way active avoidance paradigms do not provide contextual testing, likely due to challenges in performing repetitive trials of context exposure. To incorporate contextual conditioning in the two-way shuttle box, we contextually modified one of the chambers of a standard two-chamber rat shuttle box with visual cues consisting of objects and black and white stripe patterns. During the 5 training days, electrical foot shocks were delivered every 10 s in the contextually modified chamber but were signaled by a tone in the plain chamber. Shuttling between chambers prevented an incoming foot shock (avoidance) or aborted an ongoing one (escape). During contextual retention testing, rats were allowed to freely roam in the box. During auditory retention testing, visual cues were removed, and tone-signaled shocks were delivered in both chambers. Avoidance gradually replaced escape or freezing behaviors reaching 80% on the last training day in both chambers. Rats spent twice more time in the plain chamber during contextual retention testing and had 90% avoidance rates during auditory retention testing. Our modified test successfully assesses both auditory and contextual two-way active avoidance. By efficiently expanding its array of outcomes, our novel test will complement standard two-way active avoidance in mechanistic studies and will improve its applications in translational research.


Supplementation with carnitine reduces the severity of constipation: a retrospective study of patients with severe motor and intellectual disabilities.
Carnitine is an essential nutrient for the mitochondrial transport of fatty acids. Carnitine deficiency causes a variety of symptoms in multiple organs. Patients with severe motor and intellectual disabilities often have carnitine deficiency. This study aimed to determine the correlation between constipation and carnitine deficiency in them. Patients with severe motor and intellectual disabilities at our hospital were retrospectively reviewed. The correlation between level of free carnitine and severity of constipation was examined. Constipation and non-constipation groups were compared for age; sex; body mass index; bed rest period; use of anti-epileptic drugs, valproate sodium, or enteral nutrition; and serum levels of albumin, pre-albumin, totalcholesterol, free carnitine, folic acid, and trace elements. Moreover, severity of constipation before and after carnitine supplementation was assessed. Twenty-seven patients were enrolled. Of these, 14 were assigned to the constipation group and 13 to the non-constipation group. The free carnitine level was significantly correlated with severity of constipation (R = 0.7604, p<0.01). Free carnitine was significantly lower in the constipation compared with the non-constipation group (p<0.01). No other significant differences between the groups were found. The severity of constipation was significantly relieved after carnitine supplementation (p<0.001). In conclusion, carnitine supplementation could reduce the severity of constipation.