Patients Treated at Low-Volume Centers have Higher Rates of Incomplete Resection and Compromised Outcomes: Analysis of 31,129 Patients with Papillary Thyroid Cancer.
Data on the importance of margin status after total thyroidectomy for papillary thyroid cancer (PTC) remain limited. This study sought to identify factors associated with positive margins and to determine the impact of positive margins on survival for patients with PTC. The National Cancer Data Base (1998-2006) was queried for patients with PTC who had undergone total thyroidectomy. The patients were divided into three groups based on margin status (negative, microscopically positive, and macroscopically positive). Patient demographic, clinical, and pathologic features were evaluated. A binary logistic regression model was developed to identify factors associated with positive margins. A Cox proportional hazards model was developed to identify factors associated with survival. Of the 31,129 patients enrolled in the study, 91.3 % had negative margins, 8.1 % had microscopically positive margins, and 0.6 % had macroscopically positive margins. The patients with negative margins were younger and more likely to be female, white, covered by private insurance, and treated at an academic or high-volume center (p < 0.05). They had smaller tumors and were less likely to have advanced-stage disease. After multivariable adjustment, increasing patient age [odds ratio (OR) = 1.02; p < 0.01], government insurance (OR = 1.20; p < 0.01), and no insurance (OR = 1.34; p = 0.01) were associated with positive margins. Reception of surgery at a high-volume facility (OR = 0.72; p < 0.01) was protective. After multivariable adjustment, both microscopically [hazard ratio (HR), 1.49; p < 0.01] and macroscopically positive margins (HR = 2.38; p < 0.01) were associated with compromised survival. Several vulnerable patient populations have a higher risk of incomplete resection after thyroidectomy for PTC. High-risk thyroid cancer patients should be referred to high-volume centers to optimize outcomes.


Determination of prodrug treosulfan and its biologically active monoepoxide in rat plasma, liver, lungs, kidneys, muscle, and brain by HPLC-ESI-MS/MS method.
A prodrug treosulfan (TREO) is currently investigated in clinical trials for conditioning prior to hematopoietic stem cell transplantation. Bioanalysis of TREO and its active derivatives, monoepoxide (S,S-EBDM) and diepoxide, in plasma and urine underlay the pharmacokinetic studies of these compounds but cannot explain an organ pharmacological action or toxicity. Recently, distribution of TREO and S,S-EBDM into brain, cerebrospinal fluid, and aqueous humor of the eye has been investigated in animal models and the obtained results presented clinical relevance. In this paper, a selective and rapid HPLC-ESI-MS/MS method was elaborated and validated for the studies of disposition of TREO and S,S-EBDM in rat plasma, liver, lungs, kidneys, muscle, and brain. The two analytes and codeine, internal standard (IS), were isolated from 50μL of plasma and 100μL of supernatants of the tissues homogenates using ultrafiltration Amicon vials. Chromatographic resolution was accomplished on C18 column with isocratic elution. The limits of quantitation of TREO and S,S-EBDM in the studied matrices ranged from 0.11 to 0.93μM. The HPLC-MS/MS method was adequately precise and accurate within and between runs. The IS-normalized matrix effect differed among the tissues and was the most pronounced in a liver homogenate supernatant (approximately 0.55 for TREO and 0.35 for S,S-EBDM). Stability of the analytes in experimental samples was also established. The validated method for the first time enabled determination of TREO and S,S-EBDM in the six life-important tissues in rats following administration of the prodrug.


[Magnetic resonance imaging (MRI)-directed focussed ultrasound. Methods and applications in oncological treatment].
Focussed ultrasound is the only known technology that allows non-invasive local hyperthermia. Since MRI may be employed to obtain real-time temperature maps non-invasively, the combination of these two technologies offers great advantages, specifically aimed towards oncological studies. Real-time identification of the target region and accurate control of the temperature evolution during the treatment are now possible. Thermal ablation of pathological tissue, local drug delivery using thermosensitive microcarriers and controlled transgene expression using thermosensitive promoters have recently been demonstrated with this unique technology, and based on these experiments the combination of focussed ultrasound and MRI thermometry holds promise for future oncological diagnostics and treatment. In this paper we review some of the recent methodological developments as well as experimental and first clinical studies using this approach.


Impact of health care information technology on hospital productivity growth: a survey in 17 acute university hospitals.
The quantification of the added value of information technologies (IT) in the health sector is a major issue for decision-makers and health care professionals. This paper relates the application of an economic production function in hospitals with different integration levels of their clinical information systems (CIS). The study concerns 17 university hospitals within the Assistance Publique Hôpitaux de Paris group that were followed from 1998 to 2005. Using an extended Cobb-Douglas production function, yearly incomes (Y) were correlated with three inputs: capital (K), labor (L) and IT expenses (T). The results indicate that incomes are significantly and positively associated with the three input variables with elasticity coefficients: alpha, beta and gamma of 0.81, 0.17, and 0.09 that appear to be in the range of values found in secondary and tertiary sectors. The IT elasticity coefficient (gamma) is higher in the subgroup of 6 hospitals that integrate, or started to integrate, a complete CIS within the study period than in the 11 reference hospitals. In a general production function, hospital costs appear to be positively connected to the level of IT expenses, capital and labor. Calculations in two subgroups of AP-HP hospitals divided according to the importance of the IT integration level seem to indicate that the more the clinical information system is integrated, the more its influence is positive in hospital production. The results of this first survey are sufficiently encouraging to try to refine them (better granularity) and to spread them in time (over a longer period) and space (to other hospital structures).


A survivor group for battered women.
Nursing care of battered women and other survivors of violence can be effectively provided through group intervention. Using Lifton's survivor group prototype, a group of battered women met on a weekly basis for one and a half years. The model, its implementation, literature supporting the effectiveness of this kind of group, and a content analysis of the major themes of the group's discussions are presented.


Multiorgan chronic inflammatory hepatobiliary pancreatic murine model deficient in tumor necrosis factor receptors 1 and 2.
To provoke persistent/chronic multiorgan inflammatory response and to contribute to stones formation followed by fibrosis in hepatobiliary and pancreatic tissues. Tumor necrosis factor receptors 1 and 2 (TNFR1/R2) deficient mice reared in-house were given dibutyltin dichloride (DBTC) twice within 10 d by oral gavage delivery. Sham control animals received vehicle treatment and naïve animals remained untreated throughout the study. Animals were monitored daily for symptoms of pain and discomfort. The abdominal and hindpaw hypersensitivity were assessed with von Frey microfilaments. Exploratory behaviors were recorded at the baseline, after initiation of treatment, and before study termination. Histopathological changes were examined postmortem in tissues. Collagen accumulation and fibrosis were confirmed with Sirius Red staining. Animals lost weight after oral administration of DBTC and developed persistent inflammatory abdominal and hindpaw hypersensitivity compared to sham-treated controls (P < 0.0001). These pain related secondary mechanical hypersensitivity responses increased more than 2-fold in DBTC-treated animals. The drastically diminished rearing and grooming rates persisted after DBTC administration throughout the study. Gross as well as micropathology at one month confirmed that animals treated with DBTC developed chronic hepatobiliary injuries evidenced with activation of stellate cells, multifocal necrosis, fatty degeneration of hepatocytes, periportal infiltration of inflammatory cells, and prominent biliary ductal dilation. The severity of hepatitis was scored 3.7 ± 0.2 (severe) in DBTC-treated animals vs score 0 (normal) in sham-treated animals. Fibrotic thickening was extensive around portal ducts, in hepatic parenchyma as well as in lobular pancreatic structures and confirmed with Sirius Red histopathology. In addition, pancreatic microarchitecture was presented with distortion of islets, and parenchyma, infiltration of inflammatory cells, degeneration, vacuolization, and necrosis of acinar cells and distention of pancreatic ducts. Extent of pancreatic damage and pancreatitis were scored 3.6 ± 0.4 (severe) for DBTC-treated in contrast to score 0 (normal) in sham-treated animals. The gall bladder became expanded with ductal distention, and occasional bile stones were detected along with microscopic hepatic lesions. DBTC-treated animals developed splenic hypertrophy with increased weight and length (P < 0.01) along with thymic atrophy (P < 0.001). Finally, colitic lesions and colitis were prominent in DBTC-treated animals and scored 3.4 ± 0.3 (moderately severe) vs 0 (normal) for the sham-treated animals. This is the first report of chronic inflammatory multiorgan hepatobiliary pancreatitis, along with fibrosis and calculi formation induced reliably utilizing oral DBTC administration in TNFR1/R2 deficient mice.


Autonomy and the demented self.
A person who becomes demented can be considered as he presently is, a demented person, or in light of his entire life, of which dementia is but the final stage. These two perspectives can provide conflicting determinations of the person's interests and preferences, since what is best for a demented person at the time may not make his life better overall and may be directly contrary to preferences expressed while competent. Reflection on the concept of autonomy--what faculties it requires, what its point is--provides a clear understanding of the rights of the demented patient.


Clinical characteristics and risks of large congenital melanocytic naevi: a review of 31 patients at the Sydney Children's Hospital.
Large congenital melanocytic naevi (LCMN) are associated with an increased risk of malignancy and neurocutaneous melanocytosis (NCM). This Australian study aims to assess both the clinical characteristics of LCMN and the risks associated with it. The authors reviewed medical records of the Sydney Children's Hospital Dermatology Outpatient Clinic for the past 10 years and identified 31 eligible patients. A total of 14 boys and 17 girls with a median age of 0.13 years were assessed; 18 lesions were on the trunk, five were on the head, five were on the lower limbs and three were on the upper limbs. In all 20 patients had satellite naevi (the median number of the satellite naevi was 7.5). The patients were followed up for a median duration of 12 months. Central nervous system magnetic resonance imaging was performed on 19 patients and two (6.5%) were found to have NCM. Biopsies were performed on five patients; one patient (3.2%) was found to have benign proliferative nodules of undifferentiated spindle cells but no patient (0%) was found to have a malignancy. The clinical characteristics for the two patients with NCM and the patient with benign proliferative nodules suggest that the risk of both NCM and benign proliferative nodules may be greater with an increased number of satellite naevi and with the LCMN being larger in size.


Building a Unit-Level Mentored Program to Sustain a Culture of Inquiry for Evidence-Based Practice.
This study tested the effectiveness of a dynamic educational and mentoring program, facilitated by unit-level mentors, to introduce, promote, and sustain an evidence-based practice (EBP) culture among nurses in a military healthcare setting. The need to identify gaps in practice, apply principles of EBP, and advance scientific applications in the pursuit of quality nursing care is as important to military healthcare as it is in the civilian sector. The Advancing Research through Close Collaboration Model guided the intervention and study. Three instruments were used: the Organizational Readiness for System-wide Integration of Evidence-Based Practice, EBP Beliefs, and EBP Implementation scales. The study took place in 3 military hospitals simultaneously undergoing facility and staff integration. Data were collected from staff nurses in the inpatient nursing units before and after a facilitated education and mentoring intervention. Three hundred sixty nurses (38%) completed baseline, and 325 (31%) completed follow-up surveys. Scores improved on all 3 measures following implementation of the program; however, the differences were statistically significant only for the Organizational Readiness for System-wide Integration of Evidence-Based Practice scale (70.96 vs 77.63, t = -3.95, P < .01). In the paired individual pretest/posttest subsample (n = 56), scores improved significantly on all 3 instruments. Despite typically high turnover rates of military personnel and restructuring of 3 facilities during the study period, the readiness for, beliefs about, and implementation of EBP improved. This study suggests that a commitment to an EBP culture may diffuse among individuals in an organization, even while experiencing significant change. It also demonstrates that a unit-level mentored EBP program is sustainable despite changes in organizational structure and workforce composition.


Cloning and expression of the ret proto-oncogene encoding a tyrosine kinase with two potential transmembrane domains.
The nucleotide sequence of the ret proto-oncogene has been determined from cDNA clones isolated from a cDNA library of a THP-1 human monocytic leukemia cell line. Analysis of this sequence indicates that it encodes a protein which is structurally related to transmembrane receptors with a cytoplasmic tyrosine kinase domain. Unlike most growth factor receptors, it contains two hydrophobic regions which are potential transmembrane domains. Comparison of the sequence of the ret proto-oncogene with that of the ret transforming gene revealed that, in addition to the amino-terminal truncation, the last 51 carboxy-terminal amino acids of the ret proto-oncogene were replaced with 9 unrelated amino acids of the ret transforming gene. The focus forming activity of the ret cDNA, containing both amino-terminal and caboxy-terminal truncations, was approximately 13-fold higher than that of cDNA containing only the amino-terminal truncation. This suggests a possible role for the carboxy-terminal sequence in activation of transforming potential of the ret proto-oncogene. When transcription of the ret proto-oncogene was examined in a variety of mouse tissues, we detected its transcription in normal mouse spinal cord and lymphadenopathy of C3H/HeJ-gld/gld and MRL/Mp-lpr/lpr mice.


Determination of the denaturation temperature of the Spike protein S1 of SARS-CoV-2 (2019 nCoV) by Raman spectroscopy.
In the present work the temperature response of the constitutive S1 segment of the SARS-CoV-2 Spike Glycoprotein (GPS) has been studied. The intensity of the Raman bands remained almost constant before reaching a temperature of 133 °C. At this temperature a significant reduction of peak intensities was observed. Above 144 °C the spectra ceased to show any recognizable feature as that of the GPS S1, indicating that it had transformed after the denaturation process that it was subjected. The GPS S1 change is irreversible. Hence, Raman Spectroscopy (RS) provides a precision method to determine the denaturation temperature (TD) of dry powder GPS S1. The ability of RS was calibrated through the reproduction of TD of other well studied proteins as well as those of the decomposition temperature of some amino acids (AA). Through this study we established a TD of 139 ± 3 °C for powder GPS S1 of SARS-CoV-2.


Mercury hygiene.
Dentists have a moral and legal responsibility to protect themselves and their employees from high amounts of mercury vapor in the dental office. Time should be taken to train both new and existing office personnel on the nature of the problem, improved housekeeping methods, the importance of reporting problems as they occur and proper clean-up procedures.


The practical integration of a hybrid model of ultrasound-guided peripheral venous access in a large apheresis center.
Apheresis treatments require adequate venous access using peripheral intravenous (PIV) catheterization or central venous catheters (CVC). Ultrasound-guided PIV (USGPIV) can be used to decrease the need of CVC insertions for apheresis procedures. A hybrid model of USGPIV and standard of care (SOC) for PIV access was developed. Nurses performed USGPIV on all patients considered for PIV access if felt SOC PIV access was not possible. Information was collected regarding nurses' confidence with access, number of attempts required, site of access, complications, and need for CVC. In all, 226 PIV access attempts were made during a 2-month period. All apheresis procedure types were represented. A total 65% were accessed by SOC and 35% by USGPIV. USGPIV was successful on first try on 90% draw/inlet access and 87% successful on first try on return access. Access above the antecubital fossa was required in 31% of USGPIV for draw/inlet veins, and 22% of return veins. Nurses' confidence with accessing PIV was increased by USGPIV, based on 7-point Likert scale assessments. During the recording period, 2/226 (0.9%) apheresis procedures required a CVC. In a separate cohort of only hematopoietic progenitor cell collections, CVC insertion was required in 44/238 (18.5%) patients, in 7 months prior to adoption of USGPIV and 5/152 (3.3%) patients in 7 months following adoption of USGPIV. A hybrid model of using SOC and USGPIV for PIV access for apheresis procedures resulted in decreased need for CVC access, high levels of successful initial access attempts, and increased nursing confidence in PIV access.


Release and regulation of atrial natriuretic peptide (ANP).
Mammalian atrial cardiocytes synthesize and secrete a hormone called atrial natriuretic peptide (ANP), which causes natriuresis, diuresis and inhibition of smooth muscle contraction, aldosterone and renin release. Volume loading, vasoconstrictor agents, immersion in water, atrial tachycardia and high salt diets have been reported to increase the release of cardiac ANP, thereby suggesting that the peptide is released in response to an increase in atrial pressure. That stretch is an important stimulus for ANP release is also suggested by clinical studies demonstrating a direct correlation between secretion rate and atrial pressure. The experiments using isolated perfused rat heart provide direct evidence that distension of the right atrium stimulates the release of ANP. Pharmacological studies in the isolated heart point to roles of cytosolic calcium, the phosphoinositide system and the cyclic AMP pathway in the regulation of ANP release. The concentration of calcium in heart muscle cells, in addition to the length of the muscle fibers, depends on many factors such as the action of humoral substances, cardiac nerve activity and heart rate, which may all contribute to the regulation of ANP secretion.


Soldiers in psychiatric therapy: the case of Northfield military hospital 1942-1946.
This article discusses the psychiatric therapeutics of Northfield military psychiatric hospital and suggests that treatment in Northfield was characterised by ideals of citizenship typical of the period and inextricably linked to the military. The two Northfield experiments, for which Northfield has become famous, glorified the group as a social unit and promoted adaptation to the needs and values of society as the route to mental health. In the context of the Second World War, such adaptation meant accepting the duties of a soldier. In the published writings regarding the first Northfield experiment, the psychiatrist Wilfred Bion emphasised his military role in returning patients to their units, a job which he thought was best conducted by men like himself who had experience of leading men into battle. Writing about the second experiment, Tom Main emphasised the importance of including military staff in every aspect of the hospital life from therapy to administration. Some Northfield psychiatrists were less content with this strongly military approach and this led to the conflict which ended the first experiment and continued to spark disagreements throughout the hospital's existence.


Automatic Detection of Highly Organized Theta Oscillations in the Murine EEG.
Theta activity is generated in the septohippocampal system and can be recorded using deep intrahippocampal electrodes and implantable electroencephalography (EEG) radiotelemetry or tether system approaches. Pharmacologically, hippocampal theta is heterogeneous (see dualistic theory) and can be differentiated into type I and type II theta. These individual EEG subtypes are related to specific cognitive and behavioral states, such as arousal, exploration, learning and memory, higher integrative functions, etc. In neurodegenerative diseases such as Alzheimer's, structural and functional alterations of the septohippocampal system can result in impaired theta activity/oscillations. A standard quantitative analysis of the hippocampal EEG includes a Fast-Fourier-Transformation (FFT)-based frequency analysis. However, this procedure does not provide details about theta activity in general and highly-organized theta oscillations in particular. In order to obtain detailed information on highly-organized theta oscillations in the hippocampus, we have developed a new analytical approach. This approach allows for time- and cost-effective quantification of the duration of highly-organized theta oscillations and their frequency characteristics.


E3 gene manipulations affect oncolytic adenovirus activity in immunocompetent tumor models.
Oncolytic replication-selective adenoviruses constitute a rapidly growing therapeutic platform for cancer. However, the role of the host immune response and the E3 immunoregulatory genes of the human adenovirus were unknown until now. We identified four mouse carcinoma lines of variable permissivity for adenoviral gene expression, cytopathic effects and/or burst size. To determine E3 gene effects in immunocompetent tumor-bearing hosts, we injected tumors with one of three adenoviruses: Ad5 (E3 wild type), dl309 (del. E3 10.4/14.5, 14.7 kDa) or dl704 (del. E3 gp19 kDa). Compared with Ad5 and dl704, dl309 was cleared much more rapidly and/or its activity was lower in all four models. Intratumoral injection with dl309 resulted in markedly greater macrophage infiltration and expression of both tumor necrosis factor and interferon-gamma. Adenovirus replication, CD8(+) lymphocyte infiltration and efficacy were similar upon intratumoral injection with either dl704 or Ad5. E3-dependent differences were not evident in athymic mice. These findings have important implications for the design of oncolytic adenoviruses and may explain the rapid clearance of E3-10.4/14.5,14.7-deleted adenoviruses in patients.


[Calcifying epithelial odontogenic tumor: two cases report].
Calcifying epithelial odontogenic tumor (CEOT) is a rare benign epithelial tumor of odontogenic origin. CEOT is a benign but a locally infiltrative tumor. CEOT has two clinical variants: intraosseous (central) CEOT and extraosseous (peripheral) CEOT. The peripheral type is rare. In this paper, we report two cases of CEOT. The diagnoses of the cases were verified by histopathology. This study aims to explore the clinical and imaging appearances of CEOT and improve the understanding of the disease.


Global Registry of Acute Coronary Events (GRACE) hospital discharge risk score accurately predicts long-term mortality post acute coronary syndrome.
The Global Registry of Acute Coronary Events (GRACE) hospital discharge risk score (GRACE score) developed from a multinational registry involving all subsets of acute coronary syndrome (ACS) predicted 6-month survival. There is currently no validated risk model to predict mortality beyond 6 months. Of the 1143 consecutive patients with ACS admitted to coronary care unit in 2000 to 2002 (mean age, 64.9 +/- 12.6 years), 39% had ST-elevation myocardial infarction, 39% had non-ST-elevation infarction, and 22% had unstable angina. The mortality was 7.5% during index admission, 12.1% at 6 months, 14.8% at 1 year, 18.7% at 2 years, 25.0% at 3 years, and 39.2% at 4 years. The GRACE hospital discharge risk score calculated for 1057 hospital survivors discriminated survival from death at 6 months (C index, 0.81), 1 year (C index, 0.82), 2 years (C index, 0.81), 3 years (C index, 0.81), and 4 years (C index, 0.80). The risk score worked for all 3 subsets of ACS at all time points, with C index >0.75 in all analyses. A separate multivariable mortality model for these 1057 patients over the 4-years follow-up period identified 10 independent predictors of mortality. Seven were in the GRACE risk model (age, history of ischemic heart disease, heart failure, increased heart rate on admission, serum creatinine level, evidence of myonecrosis, not receiving in-hospital percutaneous coronary intervention). The GRACE postdischarge risk score contains relevant prognostic factors and accurately discriminate survivors from nonsurvivors over the longer term (up to 4 years) in all subsets of ACS patients.


Disruption of SorCS2 reveals differences in the regulation of stereociliary bundle formation between hair cell types in the inner ear.
Behavioural anomalies suggesting an inner ear disorder were observed in a colony of transgenic mice. Affected animals were profoundly deaf. Severe hair bundle defects were identified in all outer and inner hair cells (OHC, IHC) in the cochlea and in hair cells of vestibular macular organs, but hair cells in cristae were essentially unaffected. Evidence suggested the disorder was likely due to gene disruption by a randomly inserted transgene construct. Whole-genome sequencing identified interruption of the SorCS2 (Sortilin-related VPS-10 domain containing protein) locus. Real-time-qPCR demonstrated disrupted expression of SorCS2 RNA in cochlear tissue from affected mice and this was confirmed by SorCS2 immuno-labelling. In all affected hair cells, stereocilia were shorter than normal, but abnormalities of bundle morphology and organisation differed between hair cell types. Bundles on OHC were grossly misshapen with significantly fewer stereocilia than normal. However, stereocilia were organised in rows of increasing height. Bundles on IHC contained significantly more stereocilia than normal with some longer stereocilia towards the centre, or with minimal height differentials. In early postnatal mice, kinocilia (primary cilia) of IHC and of OHC were initially located towards the lateral edge of the hair cell surface but often became surrounded by stereocilia as bundle shape and apical surface contour changed. In macular organs the kinocilium was positioned in the centre of the cell surface throughout maturation. There was disruption of the signalling pathway controlling intrinsic hair cell apical asymmetry. LGN and Gαi3 were largely absent, and atypical Protein Kinase C (aPKC) lost its asymmetric distribution. The results suggest that SorCS2 plays a role upstream of the intrinsic polarity pathway and that there are differences between hair cell types in the deployment of the machinery that generates a precisely organised hair bundle.


Evaluation of a sampling method for the measurement of occupational exposures to ethylene.
In an effort to assess the scope of occupational exposures to ethylene, the Olefins Panel of the American Chemistry Council designed and conducted a research project to develop and apply a sampling and analytical method to measure workplace exposure. The method uses packed Carbosieve S-III thermal desorption tubes (Supelco, Bellefonte, Pa.) with a low sample collection flow rate. The tubes were analyzed by thermal desorption gas chromatography. The methodology was validated for both 15-min short-term exposure limit and 8-hr time-weighted average (TWA) samples in the laboratory prior to the field study. The effects of varying sampling flow rate (2, 5, 10, and 25 mL/min) and temperature (25 and 35 degrees C) on sample breakthrough time were assessed at a constant relative humidity of 90%. Breakthrough times decreased linearly with sampling flow rate and temperature. The optimal sampling flow rate and temperature at 90% relative humidity were 2 mL/ min and 25 degrees C. A full-shift TWA sample can be collected using two tubes for up to 4 hours each at a flow rate of 2 mL/min, while a STEL sample can be collected at 25 mL/min flow rate. The evaluation indicated samples can be stored under ambient conditions for a period up to 14 days without significant sample loss. Field measurements were performed at 14 petrochemical facilities within North America. The mean 8-hour TWA ethylene concentration (71 sample pairs) was 2.6 ppm (range: <0.05 to 2100 ppm). Significant ethylene concentrations were observed for only two of the 73 TWA sample pairs. Each of these two samples was obtained from the same facility, and only one tube of the sample pairs showed a high ethylene concentration (3200 ppm and 4200 ppm, respectively) for the 1600 ppm and 2100 ppm TWA sample. The first tube of each of these two sample pairs showed no detectable levels. Further, 69 of 71 sample pairs had TWA concentrations below 13 ppm. The mean of 26 short-term exposure limit samples was 16 ppm (range: <0.05 to 63 ppm), with only one sample above 50 ppm. The results of this study indicate that airborne concentrations of ethylene can be effectively measured using Carbosieve S-III packed thermal desorption tubes under typical workplace conditions.


Preliminary crystallographic X-ray data for an NAD(P)H:quinone reductase from mouse liver.
The hydrophilic form of NAD(P)H:(quinone acceptor) oxidoreductase (EC 188.8.131.52) from mouse liver cytosol has been crystallized in the presence of FAD. X-ray diffraction analysis showed these crystals to be tetragonal and to belong to the I422 space group. The unit cell measured a = b = 246.5 A and c = 70.4 A. Since the subunit molecular weight is 30,000, the asymmetric unit probably contains two pairs of dimers.


The robotic approach significantly reduces length of stay after colectomy: a propensity score-matched analysis.
Robotic surgery has helped overcome several of the inherent limitations of conventional laparoscopy. The aim of this study is to identify any short-term advantage of robotic-assisted (RC) over laparoscopic colectomy (LC) using standardized nationwide data. Patients from the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) 2012-2014 datasets who underwent elective LC or RC were compared for patient demographics, comorbidity, diagnosis, extent of colon resection, operative duration, and conversion rates. Thirty-day postoperative complications and post-discharge utilization of resources, readmission, and discharge to another facility were also evaluated. Propensity score matching was used to balance the sample size in the two groups. Of 35,839 LC and RC procedures, 2482 cases were eligible for propensity score matching for the statistically significant variables (standardized difference > 0.10) and 1241 colectomy procedures were assigned to each group. Most of the major, minor surgical, and medical postoperative complications were comparable between the two groups. However, RC was associated with reduced 30-day postoperative septic complications (2.3 vs. 4%, p = 0.02), hospital stay (mean: 4.8 vs. 6.3 days, p = 0.001), and discharge to another facility (3.5 vs. 5.8%, p = 0.01). RC was, however, associated with readmission within 30 days after surgery (9.4 vs. 9.1%, p = 0.049). Postoperative ileus, anastomotic leak, reoperation, reintubation, and mortality were equivalent between RC and LC. This propensity score-matched analysis suggests that RC is associated with some recovery benefits over LC. Greater experience with the technique may allow these advantages to counter some of the cost-related concerns that have deterred the more widespread utilization of robotic technology for colectomy.


Photoselective laser ablation of the prostate: a review of the current 2015 tissue ablation options.
Transurethral resection of the prostate (TURP) is still considered the gold standard to treat benign prostatic hyperplasia (BPH). However, photoselective vaporization of the prostate (PVP) has gained widespread acceptance as an alternative option requiring preoperative patient selection. Four laser systems are currently in use: holmium, thulium, diode and GreenLight. The goal of this article is to review the physics and the basics behind laser prostatectomies, as well as to present the most current literature concerning the results, advantages, disadvantages and international recommendations for each vaporization procedure. Holmium laser ablation of the prostate (HoLAP) and GreenLight photoselective vaporization of the prostate are an alternative to TURP for small to medium-sized prostates, providing equivalent efficacy and safety. GreenLight is also safe and effective in large-sized prostates and especially beneficial in anti-coagulated individuals compared to TURP. Thulium vaporization of the prostate (ThuVAP) and diode vaporization both require additional randomized trials and long term studies before conclusion is made, despite promising initial results. Diode vaporization provides the best hemostasis overall, but at the cost of increased complication and re-treatment rate, and thus is not recommended except in severely anti-coagulated patients. Laser vaporization is a safe and effective alternative to TURP in the treatment of benign prostatic hyperplasia (BPH) for carefully selected patients. However, further research is still needed to assess the durability of each technology.


The importance of self-observation of fecal blood in indicating a proper bowel examination.
This study presents a new model of screening for colorectal cancer. Persons aged 50 or over in a city of 160,000 inhabitants were encouraged by a newspaper campaign to act on signs of fecal blood and to come forward for examination. A quantitative immunological human hemoglobin (Hb)-specific test method was employed, and, as a simple discriminatory help to minimize perianal contamination, a constringent local ointment was used. The group of fecal bleeders was examined by colonoscopy. Altogether, 1638 persons came forward to request screening. Of these, 168 were submitted for colonoscopy, and, among those 18 colorectal cancers (11% of colonoscopies) were found. Of the cancers a significant part 28% were early cases (Dukes' A). In addition 28 adenomas were detected. The results show that there exists in the population a group of neglected fecal bleeders. Increasing the population's awareness of this symptom as a possible sign of colorectal cancer combined with prompt and proper medical investigations would lead to the detection of early cases of colorectal cancers.


Influence of time and physical activity on blood pressure and heart rate during treatment with beta-blocking agents once daily.
In a cross-over study of 52 middle-aged patients with mild to moderate essential hypertension, we have compared the effect and tolerability of 100 mg atenolol and 100 mg metoprolol given once daily. After 1 1/2 and 3 months of treatment, both systolic and diastolic blood pressure 24 hours after drug intake were significantly lower on atenolol. There were no significant differences after 3 months when blood pressure was read 3-4 hours after dose intake. During exercise, systolic blood pressure and heart rate were--at all work-loads--significantly lower on atenolol. Four patients on metoprolol and one patient on atenolol discontinued treatment owing to side-effects. The results support the need for thorough analysis of the duration of action and influence of physical activity and sympathetic tone in comparisons between presumedly equivalent antihypertensive drugs.


Foucault, surveillance, and carbon monoxide testing within stop-smoking services.
Health professionals have adopted proactive testing for early evidence of disease. Researchers have identified that this leads to enumerated understandings and shapes behavior in productive ways. Smoking-cessation advisors regularly test clients for carbon monoxide (CO), but client views of this had not previously been explored. We interviewed 23 clients of a United Kingdom-based stop-smoking service regarding their experiences of CO testing. The majority of participants were successful quitters. We used ATLAS.ti 7 as a data-management tool during structured qualitative analysis. Our findings reveal that clients believed the results of their CO tests. Many became enumerated in their understanding, and thus placed themselves in a hierarchy with other members of their group. Almost all clients found that knowing their CO test score was motivating. We conclude that additional research is needed to understand the experiences of CO testing among clients who do not quit.


Dietary Sodium Butyrate Decreases Postweaning Diarrhea by Modulating Intestinal Permeability and Changing the Bacterial Communities in Weaned Piglets.
The vast majority of substances used as alternatives to antibiotics produce inconsistent results and rarely equal the effectiveness of in-feed antibiotics. This study evaluated the effects of the combined use of sodium butyrate (SB) and reduced antibiotics in a piglet diet in promoting performance and to control weaning diarrhea. Piglets weaned at 28 d were randomly assigned to a corn-soybean meal control ration [negative control (NC)]; a similar ration with 50 mg kitasamycin/kg, 20 mg colistin sulfate/kg, and 1000 mg encapsulated SB/kg [reduced antibiotics + SB (ASB)]; or to a ration with 100 mg kitasamycin/kg and 40 mg colistin sulfate/kg [positive control (PC)] for 28 d. Performance, diarrhea incidence, intestinal permeability, and changes in the bacterial communities in the ileum and colon were determined. Weight gain and the ratio of weight gain to feed intake were significantly greater in the ASB and PC piglets than in the NC piglets (P < 0.05). Diarrhea incidence was lower in the ASB and PC piglets than in the NC piglets (P < 0.05). Urinary lactulose to mannitol ratios were 25% and 30% lower, respectively, whereas jejunal and colonic occludin protein expressions were significantly greater in the ASB and PC piglets compared with the NC piglets (P < 0.05). In the intestinal mucosa, malondialdehyde was lower in the ASB and PC piglets (by 42% and 43%, respectively), whereas tumor necrosis factor α (TNF-α) was 63% lower in the ASB piglets and 59% lower in the PC piglets compared with the NC piglets (P < 0.05). 16S ribosomal RNA gene sequence analysis revealed a higher colonic Shannon index and a lower colonic Simpson index in the ASB and PC piglets than in the NC piglets. In addition, the ASB and PC treatments caused a striking decrease in Lactobacillaceae and a noticeable increase in Clostridiaceae in the ileal and colonic lumen, as well as increases in Ruminococcaceae, Lachnospiraceae, and Bacteroidetes in the colonic lumen. Collectively, our results support an important role for SB in improving performance and decreasing diarrhea incidence in weaned piglets by modulation of intestinal permeability and the bacterial communities in the ileum and colon.


E2F-1 overexpression correlates with decreased proliferation and better prognosis in adenocarcinomas of Barrett oesophagus.
E2F-1 expression is positively associated with tumour growth in oesophageal squamous-cell carcinomas (OSCC), while it exhibits oncosuppressive features in colonic adenocarcinomas (AC). To date there are no data regarding E2F-1 expression and its relationship with tumour kinetics (proliferation, apoptosis) in adenocarcinomas that develop on Barrett oesophagus. As oesophageal adenocarcinomas occur almost exclusively in the metaplastic Barrett epithelium and the opposing E2F-1 behaviour seems to be cell and tissue-type dependent, we examined the manner in which E2F-1 acts in ACs of Barrett oesophagus. We estimated the immunohistochemical expression of E2F-1, Ki-67, caspase-3 and p53 immunohistochemical status in 35 Barrett oesophagus ACs. E2F-1 immunopositivity correlated inversely with Ki-67, by semi-serial section and statistical analysis (p = 0.023, Spearman correlation). Semi-serial section analysis revealed a direct association between E2F-1 and caspase-3 staining. No correlation was found with p53 status. Cases with higher E2F-1 immunoexpression exhibited longer survival (p = 0.047, Cox-regression). E2F-1 expression was negatively related to tumour proliferation in ACs of Barrett oesophagus. Additionally, E2F-1 immunohistochemical status correlated positively with patient survival. These findings are opposite from those seen in OSCCs, suggesting that the tumour-suppressing E2F-1 behaviour in oesophageal adenocarcinomas is possibly due to the intestinal-type nature of the metaplastic Barrett mucosa.


[Method of computing the geometrical parameters of contact lenses].
Contact lenses of home-made production are classified, and the methodology of computing their structural elements for several types of lenses is presented. Some design features of the parameters are considered with regard to the properties of the water-receptive material used for soft lenses.


Clinical Features and Evaluation in Terms of Prophylaxis of Patients With Febrile Seizures.
Febrile seizures are the most common seizure type of childhood, and prognosis is usually good. Many factors that increase the risk of recurrence and develop epilepsy have been identified. This study aims to determine the clinical characteristics of patients who were admitted with the febrile seizure, and determine the outcomes of the treatment, and the risk factors. Between January 2017 and January 2019, 147 (42.6%) female and 198 (57.4%) male patients who were admitted with febrile seizure, and aged between 3-60 months were included in the study. The mean age at the time of admission was 30.4±15.4 months, and the mean age of the first seizure was 21.2±12.8 months. Simple febrile seizure was seen in 247 (71.6%) patients, and complex febrile seizure was seen in 89 (25.8%) patients while febrile status epilepticus was present in 9 (2.6%) patients. Amongst the patients, 59.1% of them had a history of repetitive febrile seizure. First-degree relatives of thirty (8.69%) patients had a history of epilepsy, while 176 (51%) patients had a family history of febrile seizure. Two hundred and seventy-five patients (79.7%) found to have an infection, most frequently upper respiratory tract infection (53.8%), during the examination, which might cause fever. One hundred and ninety-five patients were followed without treatment, while 48.6% of the patients were treated with rectal diazepam, 23.3% with sodium valproate, 23.3% with levetiracetam and 4.6% with phenobarbital. At the end of the one-year follow-up, only four patients (1.15%) with complex febrile seizure were diagnosed with epilepsy. The age of the onset of febrile seizures, family history of febrile seizures, short episodes of febrile seizure and the presence of epilepsy in the family history were found to be the significant risk factors for repetitive seizures. Febrile seizures are generally benign and have a low risk of developing epilepsy. Determining the risk factors is essential for the treatment and follow-up plan.


Assessing the genotoxicities of sparteine and compounds isolated from Lupinus mexicanus and L. montanus seeds by using comet assay.
The genus Lupinus is widely distributed. Its seeds are used for animal and human food, and Lupinus possesses pharmacological potential because of its high content of quinolizidine alkaloids and flavonoids; however, there is little available information about its genotoxicity. We used the comet assay and staminal nuclei of Tradescantia (clone 4430) to evaluate the in vitro genotoxicity of 4 concentrations (0.01, 0.1, 0.5, and 1.0 mM) of alkaloid extracts of Lupinus mexicanus and Lupinus montanus, flavonoids of L. mexicanus, and commercial sparteine; nitrosodiethylamine was used as a positive control and untreated nuclei were used as a negative control. All concentrations of L. mexicanus and L. montanus showed significant genotoxic activity (P ≤ 0.05). A similar behavior was observed for flavonoid extracts of L. montanus except the 1.0 mM concentration. Sparteine showed genotoxic activity only at 0.5 mM. The order of genotoxicity of the compounds studied was as follows: L. mexicanus > L. montanus > flavonoids of L. montanus > sparteine. There is evident genotoxic activity in the compounds that were studied, particularly at lower concentrations (0.01 and 0.1 mM). Given the limited information about the genotoxicity of the compounds of L. mexicanus and L. montanus, further studies are necessary.


Body composition of different ethnic groups in South Africa.
South Africa is in a state of nutrition transition. As with other societies this is reflected in the emergence of overfatness, sometimes in conjunction with protein malnutrition. These phenomena may be expressed differently in a multi-ethnic society like South Africa with its major ethnic groups (Blacks, Whites, Coloureds and Indians) having varied socio-economic status. National population-based studies of coronary risk factors between 1979 and 1991 have been accessed for anthropometric data as weight and height. Cut-off points for overweight have been applied, to children to age 10 as weight-for-height greater than two Z scores by NCHS reference standards, and to those older than 15 and up to 64 years of age, BMI >= 25 and < 30, and obese >= 30 kg/m2. Data have been stratified by ethnicity, age, gender and place of residence (urban or rural) Urban Black children seem already to have a problem of overweight with a prevalence of 6-18%. For men, urban Whites have the highest prevalence of both overweight (50% in the 45-54 age group) and obesity (20% in the 55-64 age group) in all age groups except the 55-64 age groups for obesity, where Blacks have the higher prevalence (about 29%). Interestingly, the prevalence of overweight in rural women overall (39-52%) exceeds that for urban women (23-31%), although this is not the case for obesity, (prevalence age 25 and beyond, rural 24-39% and urban, 25-60%) where, indeed, in the 45-54 and 55-64 age groups, the urban prevalence exceeds the rural. This raises questions about the factors which reduce or facilitate the transition from overweight to obesity. Urban Black women seem at particular risk of this overweight-to-obesity shift and are known to have a very energy-dense diet. The extent to which overfatness contributes to other coronary risk factors is worth further investigation, given this appears to be less for Blacks than other ethnic groups.


Effectiveness and Safety of Acupuncture for Vascular Cognitive Impairment: A Systematic Review and Meta-Analysis.
Background: Acupuncture may be a promising complementary therapy for vascular cognitive impairment (VCI) and has been extensively applied in China. However, its potential effects remain uncertain, and the clinical findings are inconsistent. This review aimed to systematically appraise the overall effectiveness and safety of acupuncture in treating VCI. Methods: To investigate the effects of acupuncture on VCI from inception to February 28, 2021 using randomized clinical trials (RCTs), seven electro-databases [Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), VIP, and Wanfang] were searched. Two independent investigators identified the eligible RCTs and extracted data into predesigned forms. The risk of bias (ROB) within each individual trial was evaluated using the Cochrane Collaboration's tool. Meta-analyses were conducted for calculating comparative effects in the RevMan software (version 5.3). The strength of attained evidence was rated using the online GRADEpro approach. Results: A total of 48 RCTs involving 3,778 patients with VCI were included. The pooled data demonstrated that acupuncture was more beneficial for a global cognitive function [mean difference (MD) 1.86, 95% CI 1.19-2.54, p < 0.01] and activities of daily living (MD -3.08, 95% CI -4.81 to -1.35, p < 0.01) compared with western medicine (WM). The favorable results were also observed when acupuncture was combined with WM (MD 2.37, 95% CI 1.6-3.14, p < 0.01) or usual care (UC, MD 4.4, 95% CI 1.61-7.19, p = 0.002) in comparison with the corresponding control conditions. Meanwhile, the subgroup analysis did not indicate a statistical effect difference between manual acupuncture (MA) and electroacupuncture (EA) (inter-group I 2 < 50% and p > 0.1) when comparing acupuncture with WM. There were no significant differences in the occurrence of adverse events (AEs) between the acupuncture group and the control group (p > 0.05). Owing to the poor methodological quality and considerable heterogeneity among studies, the certainty of the evidence was low or very low. Conclusions: This review suggests that acupuncture as a monotherapy or an adjuvant therapy may play a positive role in improving the cognition and daily performance of VCI patients associated with few side effects. The difference in styles may not significantly influence its effectiveness. More rigorously designed and preregistered RCTs are highly desirable to verify the therapeutic benefits and determine an optimal acupuncture paradigm. The methodological and reporting quality of future researches should be enhanced by adhering to authoritative standardized statements. Systematic Review Registration: [PROSPERO], identifier [No. CRD42017071820].


Sexual behaviour, and knowledge and attitude towards HIV/AIDS among out of school youth in Bahir Dar Town, northwest Ethiopia.
Intervention to control the spread of HIV/AIDS in out of school youth is under way in Bahir Dar Town. This survey was therefore conducted in April 1994 to provide baseline data on sexual behaviour, knowledge and attitude towards HIV/AIDS. A total of 1115 out of school young people from eight randomly selected kebeles of the town were interviewed. Fifty one (4.6%) respondents said they have never heard of AIDS. Mean number of sexual partners for those who practised sex was 3.9 +/- 2.5. Knowledge scores were better than attitude and practice scores. Age, sex, marital status, educational status and occupation were significantly related with knowledge, attitude and practice scores (p < 0.05). The association of knowledge scores with attitude and practice scores was not statistically significant; p = 0.056 and p = 0.07, respectively. In addition to improving knowledge, emphasis should be given to other measures such as making the services accessible to the youth. A similar survey is recommended after the intervention programme is over.


Binding of Mg2+, Cd2+, and Ni2+ to liquid crystalline NaDNA: polarized light microscopy and NMR investigations.
The interaction of the divalent metal ions Mg(2+), Cd(2+), and Ni(2+) with liquid crystalline NaDNA solutions (molar ratios Me(2+)/DNA-phosphate </=0.050) was investigated by polarized light microscopy and multinuclear (31)P, (2)H, and (23)Na NMR. Our findings show that the state of the cholesteric NaDNA phase at equal MgCl(2), CdCl(2), or NiCl(2) concentration is affected in a different way and to a different extent by the nature of the divalent cation. Indeed, we found that the occurrence of an isotropic phase is markedly favored by Mg(2+), and to a lower extent by Cd(2+), and that the pitch of the cholesteric phase decreases in the presence of Cd(2+) or Ni(2+). (23)Na NMR spectroscopy also shows differences between the binding behavior of Mg(2+) and the transition metal ions in the counterion atmosphere around DNA. The results are discussed in terms of different binding modes of the metal ions.


Cytologic correlates of chemical carcinogens in respiratory tracts of dogs.
During canine respiratory carcinogenesis studies with benzo[a]pyrene (BP) and N-methyl-N-nitrosourea (NMU), a stereotypic pattern of cytomorphology characteristic for each carcinogen was observed. In the early stage, BP induced changes primarily in the cytoplasm. These changes consisted of incresaed size, basophilia, and vacuolization. In contrast, NMU induced primarily nuclear enlargement and enhanced the prominence of the nucleolus. Subsequently, cells exposed to BP demonstrated pleomorphism of the cytoplasm and nucleus, whereas cells exposed to NMU formed bizarre spindle-shaped cells. Cells were generally more scattered from one another following BP treatment than after NMU treatment. When the mucosa was exposed to NMU after the previous use of BP, the cytologic findings promptly became those characteristic of NMU.


[The information system of thermic injuries in Hungary].
The Hungarian information system for burns is reviewed and some results are referred to. Factor analysis and regression analysis of data obtained from nearly 7000 burned patients underline the fact, that, in addition to the deep burn and the patient's age, accompanying diseases and localisation of the burn will have a significant influence on the prognosis, too.


Minimizing infliximab toxicity in the treatment of inflammatory bowel disease.
Infliximab is a widely used biological agent for the treatment of inflammatory bowel disease, and has a favorable risk/benefit ratio. It is useful to know that patients treated with infliximab are exposed to developing adverse events that could be reduced with a prudent and a rational clinical approach and by optimizing the treatment protocol. PubMed (including Epub) was searched in October 2006 and again in March 2007. The high immunogenic potential of infliximab determines the antibodies that inhibit the effect of infliximab and the appearance of subsequent acute and delayed infusion reactions. Infliximab has an immunomodulatory effect, thus increasing the risk of serious and latent infections. Screening for tuberculosis, HBV, opportunistic or latent infections, heart failure, and haematological, neurological and hepatological disorders must be performed before infliximab therapy. There is no definitive evidence that infliximab increases the risk of neoplasia. Mortality in infliximab-treated patients does not appear increased compared to the controls. Infliximab safety is similar to that of conventional immunomodulators and patients treated had similar rates of mortality, neoplasm and lymphoma as patients not treated with infliximab. Patients treated with infliximab have an increased risk of serious infections but it is not related to infliximab therapy.


Is the radiation of chest pain a useful indicator of myocardial infarction? A prospective study of 541 patients.
In recent years it has been claimed that in those presenting with chest pain, the extent of pain radiation may be predictive of MI and that women's and men's pattern of pain radiation differs. This prospective study therefore investigated whether there were differences in pain radiation between those with and without MI and according to gender. Patients (n = 541) presenting to a CCU with an episode of chest pain were asked to indicate on a body map the region of pain radiation they experienced at the time of symptom onset. As expected, radiation to the left and/or to right shoulder/arm was significantly higher in the MI group. Women with MI experienced more chest pain radiating to the right arm/shoulder (P = 0.0005), upper right region (P = 0.0006) and arm/shoulder than those without MI. Additionally, women with MI also described more pain radiation in the front neck (P = 0.015) area, and the right shoulder/arm (P = 0.02) than their male counterparts. A third of these women also experienced more pain radiating to the back (P = 0.005). The premise of greater chest pain distribution amongst those with an MI could not be confirmed. Nevertheless, the study identified significant differences amongst women with MI, the discussion analyses the implications for practice.


[(Pyrimidin-5-yl)-2-propionic acids as potential anti-inflammatory agents and peripheral analgesics].
The (pyrimidin-5-yl)-2-propionic acids 3a-f have been synthetized starting from the corresponding 5-vinylpyrimidins 1a-f. They were tested for antiphlogistic and analgesic activity. Only three of these compounds showed a moderate antiinflammatory and analgesic activity.


Cornelia de Lange syndrome: To diagnose or not to diagnose in utero?
Cornelia de Lange syndrome (CdLS) is an inherited condition with a wide spectrum of phenotypic anomalies, consisting mainly of growth impairment, multi-organ abnormalities, and neurocognitive delay. Clinical diagnostic criteria after birth are well defined, whereas when to suspect the syndrome during intrauterine life still remains undefined. This review summarizes the main possible prenatal findings in CdLS, suggesting that a skilled ultrasound scan in cases of intrauterine growth restriction associated with other fetal abnormalities may improve the chance of prenatal diagnosis of CdLS, especially in families known to be at high risk. We propose that, following a sequence of detailed scans and examinations, CdLS affected fetuses could be diagnosed in utero, when one or more conditions (among them, intrauterine growth restriction, limb defects, facial abnormalities, diaphragmatic hernia, and heart diseases) are detected, and possibly confirmed by specific molecular testing. Birth Defects Research 109:771-777, 2017. © 2017 The Authors. Birth Defects Research Published by Wiley Periodicals, Inc.


Case report: Senescence as mechanism of resistance to Pembrolizumab in a Lymphoma patient who failed CD19-Targeted CAR-T cell therapy.
T cells engineered to target CD19 antigen on neoplastic B cells represent the most striking example of CAR-T cell therapy. The success rate of this therapy is affected by several limitations: target antigen loss, and/or acquisition of a senescent/exhausted phenotype by CAR and non-CAR T cells. We report on a patient affected by refractory Diffuse Large B-cell Lymphoma who was resistant to CAR T-cell therapy and to two cycles post CAR-T of pembrolizumab (PBZ) due to the evolution into a B-cell Hodgkin-like lymphoma. Owing to the CD30 expression and the Hodgkin-like phenotype, the patient was ultimately treated with Brentuximab-Vedotin and finally underwent remission. Upon PBZ treatment, 100% of circulating CAR-T+ cells showed a persistent CD8+ senescent/exhausted phenotype, while an increase in the percentage of senescent cells was found in the non-CAR CD8+ T cells compartment. PBZ is not able to reinvigorate exhausted CAR+ T cells and to confer durable clinical response. We hypothesize that the phenomenon is due to the senescent phenotype of CAR+ T cells, which did not allow PBZ-induced reactivation and proliferative rescue. The phenomenon, together with the loss of CAR-T target CD19 and the shift of non-CAR CD8+ T cells towards a senescent phenotype likely contributed to set up an immune landscape with poor antitumor capacity.


Association of the canine ATP7A and ATP7B with hepatic copper accumulation in Dobermann dogs.
Hepatic copper accumulation causes chronic hepatitis in dogs. Mutations in the copper transporters ATP7A and ATP7B were, respectively, associated with attenuation and enhancement of hepatic copper concentrations in Labrador Retrievers. There is a predisposition of Dobermanns to hepatitis with increased hepatic copper concentrations. To investigate whether the ATP7A:c.980C>T and ATP7B:c.4358G>A mutations identified in Labrador Retrievers were associated with hepatic copper concentrations in Dobermanns. Dobermanns from the Netherlands (n = 122) and the United States (n = 78). In this retrospective study, mutations in ATP7A and ATP7B were investigated as risk factors for hepatic copper accumulation in Dobermanns. Liver biopsies of 200 Dobermanns were evaluated by histochemical copper staining, quantitative copper measurement, or both modalities. ATP7A and ATP7B genotypes were obtained by Kompetitive Allele Specific PCR. A linear regression model was used to investigate an association between genotype and hepatic copper concentrations. The ATP7A:c.980C>T was identified in both Dutch (2 heterozygous individuals) and American Dobermanns. In the American cohort, the minor allele frequency of the mutation was low (.081) and a possible effect on hepatic copper concentrations could not be established from this data set. A significant association of the ATP7B:c.4358G>A variant with increased hepatic copper concentrations in Dobermanns was observed. The ATP7B:c.4358G>A variant could be a contributor to hepatic copper accumulation underlying the risk of development of copper-associated hepatitis in breeds other than the Labrador Retriever.


A Small-Molecule Inhibitor of RAD51 Reduces Homologous Recombination and Sensitizes Multiple Myeloma Cells to Doxorubicin.
We previously reported high expression of RAD51 and increased homologous recombination (HR) rates in multiple myeloma (MM) cells, and showed that genomic instability and disease progression are commensurate with HR levels. Moreover, high RAD51 expression in vivo is associated with chemoresistance and poor patient survival. Doxorubicin (DOX) is one of the most widely used drug treatments in MM chemotherapy. DOX is cytotoxic because it induces DNA double-strand breaks, which can be repaired by RAD51-mediated HR; activation of this pathway thus contributes to resistance. To investigate the role of RAD51 in MM drug resistance, we assessed the ability of B02, a small-molecule inhibitor of RAD51, to enhance DOX sensitivity of MM cells. Combining low-toxicity doses of DOX and B02 resulted in significant synthetic lethality, observed as increased apoptosis and reduced viability compared to either agent alone, or to the product of their individual effects. In contrast, the combination did not produce significant synergy against normal human CD19(+) B cells from peripheral blood. DOX induced RAD51 at both mRNA and protein levels, while arresting cells in S and G2. DOX treatment also increased the number of RAD51 foci, a marker of HR repair, so that the fraction of cells with ≥5 foci rose fourfold, whereas γH2AX foci rose far less, implying that most new breaks are repaired. When B02 treatment preceded DOX exposure, the induction of RAD51 foci was severely blunted, whereas, γH2AX foci rose significantly relative to basal levels or either agent alone. In MM cells carrying a chromosomally integrated reporter of HR repair, DOX increased HR events while B02 inhibition of RAD51 blocked the HR response. These studies demonstrate the crucial role of RAD51 in protecting MM cells from genotoxic agents such as DOX, and suggest that specific inhibition of RAD51 may be an effective means to block DNA repair in MM cells and thus to enhance the efficacy of chemotherapy.


Iranian Female Methadone Patients and the Perceived Educational Needs Related to Human Immunodeficiency Virus.
Iranian female methadone patients are at risk of human immunodeficiency virus (HIV) due to involvement in high-risk sexual behaviours and/or needle sharing. The present study aimed to explore the perceived educational needs related to HIV among a group of Iranian female methadone patients. The research design was qualitative and the participants were sampled purposively. Semi-structured interviews were conducted with 34 women and 19 clinicians in Sari, Mashhad, and Tehran, Iran. Then, qualitative content analysis was implemented. The emergence of three major themes and six minor themes was revealed. Women expressed a need to increase their knowledge including women-specific pathophysiology and disease progression and the modes of the virus transmission and prevention. Women also expressed a need to enhance their knowledge and skills related to the physical management of the virus including self-care and reproductive health. Other themes included perceived psychosocial needs including removing stigma and access to resources in the community. Women reported a wide range of educational needs from basic knowledge to advanced skills. The findings can be used in designing women-specific educational programs related to HIV in Iran. Larger studies are suggested with gender-mixed samples in the Persian context.


Macrophage-derived chemokine gene transfer results in tumor regression in murine lung carcinoma model through efficient induction of antitumor immunity.
Chemokine gene transfer represents a promising approach in the treatment of malignancies. Macrophage-derived chemokine (MDC) (CCL22) belongs to the CC chemokine family and is a strong chemoattractant for dendritic cells (DC), NK cells and T cells. Using adenoviral vectors, human MDC gene was transferred in vivo to investigate its efficacy to induce an antitumor response and to determine the immunologic mechanisms involved. We observed that intratumoral injection of recombinant adenovirus encoding human MDC (AdMDC) resulted in marked tumor regression in a murine model with pre-established subcutaneous 3LL lung carcinoma and induced significant CTL activity. The antitumor response was demonstrated to be CD4+ T cell- and CD8+ T cell-dependent. Administration of AdMDC induced chemoattraction of DC to the tumor site, facilitated DC migration to draining lymph nodes or spleen, and finally activated DC to produce high levels of IL-12. Furthermore, a significant increase of IL-4 production within the tumors was observed early after the AdMDC administration and was followed by the increase of IL-12 and IL-2 production. The levels of IL-2, IL-12 and IFN-gamma in serum, lymph nodes and spleen were also found to be higher in mice treated with AdMDC as compared with that in AdLacZ- or PBS-treated mice. The antitumor response induced by AdMDC was markedly impaired in IL-4 knockout mice, suggesting an important role of IL-4 in the induction of antitumor immunity by MDC. These results suggest that MDC gene transfer might elicit significant antitumor effects through efficient induction of antitumor immunity and might be of therapeutic potentials for cancer.


Experimental microdissection enables functional harmonisation of pancreatic cancer subtypes.
Pancreatic ductal adenocarcinoma (PDA) has among the highest stromal fractions of any cancer and this has complicated attempts at expression-based molecular classification. The goal of this work is to profile purified samples of human PDA epithelium and stroma and examine their respective contributions to gene expression in bulk PDA samples. We used laser capture microdissection (LCM) and RNA sequencing to profile the expression of 60 matched pairs of human PDA malignant epithelium and stroma samples. We then used these data to train a computational model that allowed us to infer tissue composition and generate virtual compartment-specific expression profiles from bulk gene expression cohorts. Our analysis found significant variation in the tissue composition of pancreatic tumours from different public cohorts. Computational removal of stromal gene expression resulted in the reclassification of some tumours, reconciling functional differences between different cohorts. Furthermore, we established a novel classification signature from a total of 110 purified human PDA stroma samples, finding two groups that differ in the extracellular matrix-associated and immune-associated processes. Lastly, a systematic evaluation of cross-compartment subtypes spanning four patient cohorts indicated partial dependence between epithelial and stromal molecular subtypes. Our findings add clarity to the nature and number of molecular subtypes in PDA, expand our understanding of global transcriptional programmes in the stroma and harmonise the results of molecular subtyping efforts across independent cohorts.


Promotion Effect of Apo-9'-fucoxanthinone from Sargassum muticum on Hair Growth via the Activation of Wnt/β-Catenin and VEGF-R2.
This study was conducted to evaluate the effects of Sargassum muticum extract and apo-9'-fucoxanthinone, a principal component of S. muticum, on hair growth. When rat vibrissa follicles were treated with S. muticum extract for 21 d, the hair-fiber lengths for the vibrissa follicles increased significantly. Treatment with the S. muticum extract and the EtOAc fraction of the S. muticum extract markedly increased the proliferation of dermal papilla cells (DPCs) and decreased the 5α-reductase activity. In addition, the EtOAc fraction of the S. muticum extract significantly promoted anagen initiation in C57BL/6 mice. Especially, apo-9'-fucoxanthinone, an active constituent from the S. muticum extract, caused an increase in DPC proliferation and a decrease in 5α-reductase activity. To elucidate the molecular mechanisms of apo-9'-fucoxanthinone on the proliferation of DPCs, we examined the level of various signaling proteins. Apo-9'-fucoxanthinone increased the level of vascular endothelial growth factor receptor-2 (VEGF-R2), Wnt/β-catenin signaling proteins such as phospho(ser9)-glycogen synthase kinase-3β (GSK-3β) and phospho(ser552)-β-catenin, whereas apo-9'-fucoxanthinone did not affect the transforming growth factor-β (TGF-β) signaling proteins such as Smad2/3. These results suggest that apo-9'-fucoxanthinone from S. muticum could have the potential for hair growth with DPC proliferation via the activation of Wnt/β-catenin signaling and the VEGF-R2 pathway.


Glycogen synthase kinase-3 regulation of urinary concentrating ability.
Glycogen synthase kinase-3 (GSK3) is an enzyme that is gaining prominence as a critical signaling molecule in the epithelial cells of renal tubules. This review will focus on recent findings exploring the role of GSK3 in renal collecting ducts, especially its role in urine concentration involving vasopressin signaling. Recent studies using inhibition or tissue-specific gene deletion of GSK3 revealed the mechanism by which GSK3 regulates aquaporin 2 water channels via adenylate cyclase or the prostaglandin-E2 pathway. In other studies, postnatal treatment with lithium, an inhibitor of GSK3, increased cell proliferation and led to microcyst formation in rat kidneys. These studies suggest that loss of GSK3 activity could interfere with renal water transport at two levels. In the short term, it could disrupt vasopressin signaling in collecting duct cells and in the long term it could alter the structure of the collecting ducts, making them less responsive to the hydro-osmotic effects of vasopressin. Ongoing studies reveal the crucial role played by GSK3 in the regulation of vasopressin action in the renal collecting ducts and suggest a possible use of GSK3 inhibitors in disease conditions associated with disrupted vasopressin signaling.


Analysis of sequence polymorphism and population structure of tomato chlorotic dwarf viroid and potato spindle tuber viroid in viroid-infected tomato plants.
The sequence polymorphism and population structure of Tomato chlorotic dwarf viroid (TCDVd) (isolate Trust) and Potato tuber spindle viroid (PSTVd) (isolate FN) in tomato plants were investigated. Of the 9 and 35 TCDVd clones sequenced from 2 different TCDVd-infected plants, 2 and 4 sequence variants were identified, respectively, leading to a total of 4 sequence variants of 360 nucleotides in length. Variant I was identical to AF162131, the first TCDVd sequence to be reported, and the rest exhibited 1 to 3 nucleotide differences, all in the T(R) domain, from AF162131/variant I. Of the 33 and 29 PSTVd clones sequenced from 2 different PSTVd-infected plants, 8 and 9 sequence variants were found, respectively, leading to a total of 15 variants ranging in length from 356 to 359 nucleotides. The variant I was identical to EF044303, a PSTVd reported in Russia. The rest exhibited 1 to 11 nucleotide differences scattering in all five domains from EF044303/variant I. The results demonstrated for the first time that TCDVd, like many other viroids including PSTVd, exists in host plants as a collective group comprised of various sequence variants. However, in comparison to PSTVd, TCDVd is less polymorphic in tomato plants as fewer variants and lower haplotype/nucleotide diversities were observed.


T1 mapping for detection of left ventricular myocardial fibrosis in hypertrophic cardiomyopathy: a preliminary study.
To investigate the diagnostic value of T1 mapping imaging of evaluating fibrosis in patients with hypertrophic cardiomyopathy (HCM). 21 subjects with HCM and 18 healthy volunteers underwent conventional late gadolinium enhancement (LGE) imaging and T1 mapping imaging. The region of myocardium in HCM is divided into remote area of LGE, peri-LGE, LGE (halo-like LGE and typical patchy LGE). These regions combined with normal volunteers' myocardium were calculated by the reduced percent of T1 value (RPTV). The RPTV in healthy volunteers was no significant comparing with that in the remote area of LGE in HCM subjects (3.98 ± 3.19 vs. 3.34 ± 2.75, P>0.05). There were significant statistical differences in pairwise among the remote area of LGE, peri-LGE, halo-like LGE and typical patchy LGE in the RPTV (P<0.0001). ROC curves indicated that the T1 mapping imaging has a greater area under the curve comparing with that of traditional LGE imaging (0.975 ± 0.07 vs. 0.753 ± 0.26, P<0.0001). HCM has a high prevalence of fibrosis and with varying severity. T1 mapping imaging can be a useful method to evaluate the severity of the fibrosis in HCM.


Early life experience influences dispersal in coyotes (Canis latrans).
Natal dispersal plays an important role in connecting individual animal behavior with ecological processes at all levels of biological organization. As urban environments are rapidly increasing in extent and intensity, understanding how urbanization influences these long distance movements is critical for predicting the persistence of species and communities. There is considerable variation in the movement responses of individuals within a species, some of which is attributed to behavioral plasticity which interacts with experience to produce interindividual differences in behavior. For natal dispersers, much of this experience occurs in the natal home range. Using data collected from VHF collared coyotes (Canis latrans) in the Chicago Metropolitan Area we explored the relationship between early life experience with urbanization and departure, transience, and settlement behavior. Additionally, we looked at how early life experience with urbanization influenced survival to adulthood and the likelihood of experiencing a vehicle related mortality. We found that coyotes with more developed habitat in their natal home range were more likely to disperse and tended to disperse farther than individuals with more natural habitat in their natal home range. Interestingly, our analysis produced mixed results for the relationship between natal habitat and habitat selection during settlement. Finally, we found no evidence that early life experience with urbanization influenced survival to adulthood or the likelihood of experiencing vehicular mortality. Our study provides evidence that early life exposure influences dispersal behavior; however, it remains unclear how these differences ultimately affect fitness.


Ductal eccrine carcinoma of the axilla: a diagnostic pitfall.
Ductal eccrine carcinoma (DEC) is a rare sweat gland carcinoma with ductular differentiation. Clinically, it is characterized by a slowly growing, hardened plaque or nodule predominantly located on the head and neck. Histologically, DEC shares similar features to invasive breast carcinoma, thus causing great diagnostic challenges. We report a 69-year-old woman who presented with a hardened plaque on the axilla. A skin biopsy was performed and metastatic invasive breast carcinoma could not be ruled out. Complete excision and further workup were subsequently conducted, leading to the diagnosis of estrogen receptor positive DEC with associated axillary lymph node metastases. The patient received adjuvant radiotherapy to the left axilla and was started on oral letrozole. She is disease-free 14 months after initial diagnosis.


Impact of matrix stiffness on fibroblast function.
Chronic non-healing wounds, caused by impaired production of growth factors and reduced vascularization, represent a significant burden to patients, health care professionals, and health care system. While several wound dressing biomaterials have been developed, the impact of the mechanical properties of the dressings on the residing cells and consequently on the healing of the wounds is largely overlooked. The primary focus of this study is to explore whether manipulation of the substrate mechanics can regulate the function of fibroblasts, particularly in the context of their angiogenic activity. A photocrosslinkable hydrogel platform with orthogonal control over gel modulus and cell adhesive sites was developed to explore the quantitative relationship between ECM compliance and fibroblast function. Increase in matrix stiffness resulted in enhanced fibroblast proliferation and stress fiber formation. However, the angiogenic activity of fibroblasts was found to be optimum when the cells were seeded on compliant matrices. Thus, the observations suggest that the stiffness of the wound dressing material may play an important role in the progression of wound healing.


The mechanism of ergometrine-induced coronary arterial spasm: in vitro studies on canine arteries.
The mechanism by which ergometrine provokes coronary vasospasm was investigated in vitro. Changes in tension were monitored isometrically on spiral strips of freshly obtained coronary (ventricular and circumflex branches) and basilar arteries from dogs. Cumulative concentration-response curves were established for noradrenaline, adrenaline, 5-hydroxytryptamine (5-HT), and ergometrine. The catecholamines either contracted or relaxed the coronary vascular smooth muscle by stimulating alpha- or beta-adrenoceptors, respectively, whereas both 5-HT and ergometrine consistently induced contraction of coronary arteries. In order to antagonize ergometrine-induced contraction on circumflex coronary arteries, appromimately 60-fold greater concentrations of phentolamine were required compared to those necessary for antagonism of noradrenaline. The concentration-response curve for noradrenaline was unchanged by ergometrine, indicating that the two compounds combine with different receptors. The use of the antagonists phentolamine, indoramine, pimozide, pizotifen, and methysergide provided evidence that ergometrine and 5-HT induce contraction of coronary arteries by stimulating the same type of 5-HT receptor, which, however, seems to be different from the 5-HT receptor present in basilar arteries. It is suggested that in Prinzmetal's variant form of angina, ergometrine can provoke coronary vasospasm by increasing the tone of the coronary vascular smooth muscle via stimulation of 5-HT receptors, thus reinforcing sympathetic coronary vascular tone.


Rhinitis medicamentosa.
The diagnosis of rhinitis medicamentosa was made in 130 patients seen over a 10 year period from July 1967 to June 1977. There was an incidence of 1% in our otolaryngological practice. Patients had been taking the causal medication for an average of 21.4 months. There were 73 males and 57 females with the peak incidence in young and middle-age adults. The primary offending medications were decongestant nasal sprays in 85 patients, decongestant drops in 33, and a combination of these drugs in 12 patients. The major reasons for self-medication were 1. deviated nasal septum in 40 patients, 2. an acute upper respiratory infection in 33, 3. allergy in 18, 4. miscellaneous causes in 24 and 5. unknown in 15 patients. The initial management in addition to avoidance of the medication consisted of systemic antibiotics, decongestants, antihistamines, and sedatives depending on the severity of the rhinitis and the presence of secondary infection. Later treatment consisted of correction of the deviated septums, allergic management, and supportive care. Eight patients were considered to have complications of the disease by development of chronic ethmoiditis and nasal polyposis. The pharmacologic properties of the causal agents are thoroughly reviewed as they relate to the pathogenesis of this disease. It is felt that the ready commercial availability and limited clinical value of the topical nasal sprays and drops represents a certain risk to all patients using them.


Stability of Enzymatic Biosensors for Wearable Applications.
Technological evolution in wearable sensors accounts for major growth and transformation in a multitude of industries, ranging from healthcare to computing and informatics to communication and biomedical sciences. The major driver for this transformation is the new-found ability to continuously monitor and analyze the patients' physiology in patients' natural setting. Numerous wearable sensors are already on the market and are summarized. Most of the current technologies have focused on electrophysiological, electromechanical, or acoustic measurements. Wearable biochemical sensing devices are in their infancy. Traditional challenges in biochemical sensing such as reliability, repeatability, stability, and drift are amplified in wearable sensing systems due to variabilities in operating environment, sample/sensor handling, and motion artifacts. Enzymatic sensing technologies, due to reduced fluidic challenges, continue to be forerunners for converting into wearable sensors. This paper reviews the recent developments in wearable enzymatic sensors. The wearable sensors have been classified in three major groups based on sensor embodiment and placement relative to the human body: 1) on-body, 2) clothing/textile-based biosensors, and 3) biosensor accessories. The sensors, which come in the forms of stickers and tattoos, are categorized as on-body biosensors. The fabric-based biosensor comes in different models such as smart-shirts, socks, gloves, and smart undergarments with printed sensors for continuous monitoring.


Development of a Phase-Transfer-Catalyzed, [2,3]-Wittig Rearrangement.
An investigation into the use of phase-transfer catalysis for the [2,3]-sigmatropic rearrangement of allyloxy carbonyl compounds is described. Initial studies focused on identifying viable substrate classes that would undergo selective [2,3]-rearrangement under phase-transfer catalysis. Under certain conditions, the [2,3]-sigmatropic rearrangement of allyloxy carbonyl compounds takes place in the presence of a phase-transfer agent, providing a rare example of a phase-transfer-catalyzed unimolecular reaction. In the course of this investigation, it was found that catalysis is dependent on several variables including base concentration, catalyst structure, and substrate lipophilicity. Preliminary testing of chiral, nonracemic phase-transfer catalysts has shown promising levels of enantioselectivity for future development.


Low FODMAP Diet and Probiotics in Irritable Bowel Syndrome: A Systematic Review With Network Meta-analysis.
Background: Probiotic and low fermentable oligosaccharide, disaccharide, monosaccharide, and polyol (FODMAP) diet are two commonly used management approaches for patients with irritable bowel syndrome (IBS). We aimed to evaluate the most effective combinations and components among different probiotics or low FODMAP diet through component network meta-analysis (NMA). Methods: We searched Embase, Ovid Medline, and Web of Science from inception to 21 January 2021. Randomized controlled trials (RCTs) examining the efficacy of probiotics and low FODMAP diet for IBS were included, with placebo, sham diet, or conventional treatments as controls. Binary outcomes were compared among treatments using the relative ratio (RR). A minimally contextualized framework recommended by the GRADE group was used to evaluate the certainty of evidence. The primary efficacy outcome was the relief of global IBS symptoms, and the secondary efficacy outcome was the reduction in IBS symptom scores or abdominal pain scores. Key Results: We included 76 RCTs (n = 8058) after screening 1940 articles. Eight RCTs were classified as low risk of bias. Standard network meta-analysis (NMA) showed that Lactobacillus (RR 1.74, 95% CI 1.22-2.48) and Bifidobacterium (RR 1.76, 95% CI 1.01-3.07) were the most effective for the primary efficacy outcome (high certainty evidence); component NMA showed that Bacillus (RR 5.67, 95% CI 1.88 to 17.08, p = 0.002) and Lactobacillus (RR 1.42, 95% CI 1.07 to 1.91, p = 0.017) were among the most effective components. The results of standard NMA and CNMA analysis of the improvement of overall IBS symptom scores or abdominal pain scores were consistent with this finding. Conclusion: Lactobacillus was the most effective component for the relief of IBS symptoms; Bifidobacterium and Bacillus were possibly effective and need further verification. Systematic Review Registration: website, identifier registration number.


Susceptibility of coccidioides immitis, Candida albicans, and Cryptococcus neoformans to amphotericin B, flucytosine, and clotrimazole.
Toxicity and failure of treatment with amphotericin B are stimuli for researchers to evaluate alternative antifungal antimicrobics. Also, data from susceptibility tests of Coccidioides immitis are sparse. With use of a defined, synthetic culture medium, C. immitis (25 strains). Candida albicans (21 strains), and Cryptococcus neoformans (21 strains) were tested against flucytosine, clotrimazole, and amphotericin B. Molecule for molecule, the sequency of activity was: clotrimazole greater than amphotericin B greater than flucytosine (totally inactive) C. immitis; and clotrimazole greater than amphotericin B greater than flucytosine with C. albicans and C. neoformans. With four strains of C. immitis, the minimal inhibitory concentration (of amphotericin B) was the same when inocula of arthrospores were tested as when corresponding spherules/endospores were tested simultaneously and identically. The clinical outcome of coccidioidomycosis in 17 patients treated with amphotericin B correlated best with minimal inhibitory concentration after incubation of cultures for 48 hr; a favorable response was associated with minimal inhibitory concentrations of less than or equal 1.0 mug/ml. Because clinical isolates of fungi appear to vary in susceptibility, in vitro tests may have clinical utility.


Delayed-type hypersensitivity anergy in human immunodeficiency virus-infected persons screened for infection with Mycobacterium tuberculosis.
A total of 479 human immunodeficiency virus (HIV)-infected persons at an HIV clinic in Florida and a tuberculosis clinic in New Jersey were skin-tested with tuberculin, tetanus toxoid, mumps antigen, and Candida antigen in a study of the prevalence of delayed-type hypersensitivity (DTH) anergy and the usefulness of two-step tuberculin testing in this population. Of the patients tested, 12% had a positive (> or = 5-mm) response to tuberculin; 57%, 45%, and 35% had a positive (> or = 3-mm) response to Candida antigen, tetanus toxoid, and mumps antigen, respectively; and 31% were anergic (< 3 mm of induration in response to each antigen). In a multivariate logistic regression model, anergy was significantly associated with a history of Kaposi's sarcoma, Pneumocystis carinii pneumonia, or oral candidiasis and with White race. Anergy was four times and 15 times as likely for persons with CD4+ T-lymphocyte counts of 200-400/mm3 and < 200/mm3, respectively, as for persons with > 499 CD4+ T lymphocytes/mm3. Of 103 patients who were tuberculin-tested a second time after their initial test result was negative, seven had > or = 5 mm of induration in response to the second test; only one of these patients was anergic at the initial screening. The findings of this study indicate that DTH antigens should be used in conjunction with tuberculin testing and that two-step tuberculin testing is not an alternative to anergy testing but may be useful for the detection of infection with Mycobacterium tuberculosis in nonanergic HIV-infected patients.


The apolipoprotein E gene and Taq1A polymorphisms in childhood obesity.
Obesity is a multifactorial disease that is influenced by genetic and environmental factors. The apolipoprotein E (Apo E) polymorphism has been reported to influence some lipid profile abnormalities associated with obesity in childhood. In this study, the relationship between the Apo E gene and Taq1A polymorphisms with childhood obesity has been studied. Regarding the Apo E genotypes, e3/4 was the most frequent in both the patient and control groups. Further, there was a significance between the Apo E genotypes with low density lipoprotein and total cholesterol levels. However, no relationship was found between the Taq1A polymorphism and obesity. In conclusion, polygenic inheritance should be kept in mind when dealing with childhood obesity.


[Stature estimation from length of tibias and fibulas measured in computed radiography of living body].
By measuring lengths of tibias and fibulas in computed radiography (CR) of living body, regression formulae for stature estimation were obtained from these measurements that were adapted to the population of northern adults of Han. The length of tibias and fibulas were measured in radiography, including 422 subjects (207 men and 215 women). The body height of each subject was also recorded. Linear regression analysis between body height and the length of tibias and fibulas , analysis of variance of hypothesis test of linear regression model and t-test of the partial regression coefficient were applied to establish the regression equations for stature estimation. Then the paired t-test between the predictive value and the actual body height, the residual analysis, the tests of equal scedasticity and colinearity had been done to evaluate whether the equations accord with the model. Thirty five regression equations which were statistical significant were obtained. The multiple correlation coefficient was from 0.909 to 0.823 and the standard error of the estimation was between 2.48-3.87 cm. The lengths of tibias and fibulas on the CR films could be helpful to estimate stature. These equations could be used to estimate the body height of the Han population in North China.


Children's individual voices are required for adequate management of fear and pain during hospital care and treatment.
Children often report both fear and pain in conjunction with clinical care and treatment. Interventions developed in the field have still not been sufficient to prevent and relieve children's fear and pain. More knowledge, from children's own perspectives, is needed about how they deal with their experiences. To explore child-identified strategies that children use to manage fear and pain during needle-related medical procedures in hospital. Interviews with children, age 4-12 years, with experience of hospital care were analysed qualitatively using content analysis. Children have self-identified strategies for dealing with fear and pain during hospital care and treatment. The strategies vary depending on examination or treatment and on how the child felt at that particular day. Children describe what they can do themselves, how adults can empower them and support from surroundings as strategies that give them a choice and a voice. Children wished to have influence, decide when and how information should be given, scream out loud or squeeze something hard, to deal with fear and pain. The results also show that children tried to be brave, gain control and think positively. Something nice to look at and opportunities to play with others also contributed. Strategies vary between children and are used differently on different occasions. Healthcare professionals pose a threat to the child's needs and ability to use their strategies due to lack of knowledge of the child's chosen strategies.


A Proteomic Landscape of Candida albicans in the Stepwise Evolution to Fluconazole Resistance.
As an opportunistic fungal pathogen, Candida albicans is a major cause of superficial and systemic infections in immunocompromised patients. The increasing rate of azole resistance in C. albicans has brought further challenges to clinical therapy. In this study, we collected five isogenic C. albicans strains recovered over discrete intervals from an HIV-infected patient who suffered 2-year recurrent oropharyngeal candidiasis. Azole resistance was known from the clinical history to have developed gradually in this patient, and this was confirmed by MIC assays of each strain. Proteomic techniques can be used to investigate more comprehensively how resistance develops in pathogenic fungi over time. Our study is the first to use tandem mass tag (TMT) labeling combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) technology to investigate the acquired resistance mechanisms of serial C. albicans isolates at the proteomic level. A total of 4,029 proteins have been identified, of which 3,766 have been quantified. Compared with Ca1, bioinformatics analysis showed that differentially expressed proteins were mainly associated with aspects such as the downregulation of glycolysis/gluconeogenesis, pyruvate metabolism, fatty acid degradation, and oxidative stress response proteins in all four subsequent strains but, remarkably, the activation of amino acid metabolism in Ca8 and Ca14 and increased protection against osmotic stress or excessive copper toxicity, upregulation of respiratory chain activity, and suppression of iron transport in Ca17. By tracing proteomic alterations in this set of isogenic resistance isolates, we acquire mechanistic insight into the steps involved in the acquisition of azole resistance in C. albicans.


Fine- and hyperfine-structure effects in molecular photoionization. II. Resonance-enhanced multiphoton ionization and hyperfine-selective generation of molecular cations.
Resonance-enhanced multiphoton ionization (REMPI) is a widely used technique for studying molecular photoionization and producing molecular cations for spectroscopy and dynamics studies. Here, we present a model for describing hyperfine-structure effects in the REMPI process and for predicting hyperfine populations in molecular ions produced by this method. This model is a generalization of our model for fine- and hyperfine-structure effects in one-photon ionization of molecules presented in Paper I [M. Germann and S. Willitsch, J. Chem. Phys. 145, 044314 (2016)]. This generalization is achieved by covering two main aspects: (1) treatment of the neutral bound-bound transition including the hyperfine structure that makes up the first step of the REMPI process and (2) modification of our ionization model to account for anisotropic populations resulting from this first excitation step. Our findings may be used for analyzing results from experiments with molecular ions produced by REMPI and may serve as a theoretical background for hyperfine-selective ionization experiments.


Iron-endocrine pattern in patients with beta-thalassaemia.
Patients with beta-thalassaemia (major, minor, and in association with sickle cell gene) frequently suffer from growth retardation and delayed sexual development. This is believed to be due, at least in part, to a direct effect of iron overload on the endocrine mechanisms of puberty. The role of iron overload remains speculative in relation to the disease severity and ethnic variations. This study determined the level of testosterone, cortisol, luteinizing hormone (LH), follicle stimulating hormone (FSH), free thyroxine (T4), tri-iodothyronine (T3), growth hormone (GH), iron, ferritin, and haematological parameters in 44 beta-thalassaemia patients (21 = beta-thal. major, 23 beta-thal minor), 25 Hb S/beta zero-thalassaemia patients, and 50 normal controls with age range 2-15 years. The iron endocrine status and haematological findings were evaluated, and the results were correlated and compared with age- and sex-matched controls. In comparison with controls the beta-thalassaemia-major and the Hb S/beta zero-thalassaemia patients had a significantly higher level of plasma ferritin (P < 0.01) while the mean level of total haemoglobin was significantly lower. The level of LH, FSH, testosterone, and plasma cortisol were lower in both beta-thalassaemia-major and Hb S/beta zero-thalassaemia patients with a negative correlation with plasma ferritin level. Free T3 and T4 were raised, but the difference was not statistically significant. The data demonstrate the occurrence of impaired endocrine function in the beta-thalassaemia and Hb S/beta zero-thalassaemia patients.