Early changes in tear film protein profiles after femtosecond LASIK surgery.
Femtosecond laser-assisted in situ keratomileusis (LASIK) has proven to be an efficacious, predictable, and safe procedure for the correction of refractive errors. We examined the early tear protein changes of patients undergoing LASIK surgery in order to better understand the mechanisms and proteins related to laser corneal surgery and initial recovery. Corneal flaps were created with Ziemer FEMTO LDV Z6 I femtosecond laser and stroma was ablated using Wavelight EX500 excimer laser. Tear samples were collected preoperatively as well as 1.5 h and 1 month after LASIK treatment using glass microcapillary tubes. Relative quantification of tear proteins was performed with sequential window acquisition of all theoretical fragment ion spectra mass spectrometry (SWATH-MS). SWATH-MS revealed that 158 proteins had altered expression levels 1.5 h after the operation. Two-thirds of these proteins, mostly connected to migration and inflammation response, returned to preoperative levels within the first postoperative month. The other proteins, which did not return to baseline levels, included proteins connected to for example epithelial barrier function. We also identified several proteins, which correlated with surgical variables, such as the amount of correction, flap thickness and flap diameter. The present study showed that an uneventful femtosecond LASIK refractive surgery induced a significant immune cell migration and inflammation-associated changes in tear proteomics profile quickly after the operation, but the expression of most proteins recovered almost completely to the preoperative levels within the first month. The individual proteins identified in our study are potential targets for the follow-up and modification of LASIK-induced biochemical processes.


Upper-body morbidity following breast cancer treatment is common, may persist longer-term and adversely influences quality of life.
Impairments in upper-body function (UBF) are common following breast cancer. However, the relationship between arm morbidity and quality of life (QoL) remains unclear. This investigation uses longitudinal data to describe UBF in a population-based sample of women with breast cancer and examines its relationship with QoL. Australian women (n=287) with unilateral breast cancer were assessed at three-monthly intervals, from six- to 18-months post-surgery (PS). Strength, endurance and flexibility were used to assess objective UBF, while the Disability of the Arm, Shoulder and Hand questionnaire and the Functional Assessment of Cancer Therapy-Breast questionnaire were used to assess self-reported UBF and QoL, respectively. Although mean UBF improved over time, up to 41% of women revealed declines in UBF between six- and 18-months PS. Older age, lower socioeconomic position, treatment on the dominant side, mastectomy, more extensive lymph node removal and having lymphoedema each increased odds of declines in UBF by at least two-fold (p<0.05). Lower baseline and declines in perceived UBF between six- and 18-months PS were each associated with poorer QoL at 18-months PS (p<0.05). Significant upper-body morbidity is experienced by many following breast cancer treatment, persisting longer term, and adversely influencing the QoL of breast cancer survivors.


[Use of the free forearm flaps in cervicofacial surgery. Apropos of 5 cases and review of the literature].
The free fasciocutaneous forearm flap has been described only recently. Five cases of pharyngeal or oral repair with a forearm flap (FAF) are reported and used as a basis to discuss anatomical features and the technique used for removal of the flap. The relevant literature is reviewed. The FAF appears to be the flap of choice for reparative surgery of pharynx or mouth regions in oncology, the principal advantages of this flap being: fineness, flexibility and plasticity of the skin, reliability and lack of morbidity, and function effectiveness with respect to phonation and feeding. Indications for forearm and myocutaneous flaps in oncology of upper respiratory and digestive tracts are assessed critically, other indications for the forearm flap being cutaneous repair of cervicofacial lesions due to tumor or injury. The forearm flap is of pronounced value for cervicofacial repair surgery and constitutes a new step in the plastic conception of these repair procedures.


[Liu Jie attends Henan planned parenthood meeting].
Henan scored excellent results in planned parenthood work last year. The natural population growth rate fell to 9.53/1000, a fall of 3.35/1000 from the 1979 level. The province victoriously fulfilled the population plan assigned by the state. Some 320,000 couples with 1 child have taken out single-child certificates. The provincial CCP Committee recently convened a planned parenthood meeting. Provincial CCP Committee 1st Secretary Liu Jie and Secretaries Dai Suli and Zhang Shude spoke at the meeting. Li Xiuzhen, deputy director of the State Council's planned parenthood leading group and director of its administrative office, also attended and spoke at the meeting. The speakers stressed: Party committees and government at all levels must strengthen leadership over planned parenthood, put this work in an important place on their agenda, resolve to promote this work, and succeed in grasping the 2 items of production together. We must further publicize and implement the Central Committee's open letter, vigorously advocate that each couple should have only 1 child, strictly control the birth of a 2nd child, and take resolute measures to prevent the birth of more than 2. We must put ideological education in the primary position. CCP and CYL members and cadres at all levels must take the lead in practicing planned parenthood.


Diagnosis and management of duodenal obstruction due to renal cell carcinoma.
Two cases of duodenal obstruction secondary to renal cell carcinoma are described. One case had delayed metastasis to duodenum four years after right radical nephrectomy and the second case had a large right renal cell carcinoma with duodenal involvement. The possibility of duodenal involvement or metastasis should be kept in mind in any patient presenting with upper gastrointestinal obstructive symptoms and with right sided renal tumour or radical nephrectomy in the past. Whenever suspected, radiography and if required endoscopic assessment should be supplemented to diagnose this condition. Extensive local disease or presence of concurrent metastasis usually rules out the possibility of cure. We describe the clinico-radiological features of this condition along with a review of the literature.


Tricycles by a new Ugi variation and Pictet-Spengler reaction in one pot.
Subsequent mild cyclization of aromatic substrates by Pictet-Spengler condensation stereoselectively gave new tricyclic compounds. Examples are described in decent yields over two steps in one pot, and a crystal structure is also presented to support the proposed structures.


The role of Na+/H+ exchange and growth factors in pulmonary artery smooth muscle cell proliferation.
Chronic hypoxia produces pulmonary hypertension, in part because of hypertrophy and hyperplasia of pulmonary artery smooth muscle cells (PA SMC). Platelet-derived growth factor (PDGF) and epidermal growth factor (EGF) have been shown to stimulate SMC proliferation and may be involved in these vascular changes. Both factors cause a rise in intracellular pH (pHi) in systemic vascular SMC through stimulation of the Na+/H+ exchanger, an event that has been thought to be permissive, allowing cell proliferation in response to the growth factor. The present studies examined the possibility that the activation of Na+/H+ exchange is involved in the PA SMC mitogenic response to these growth factors. Na+/H+ exchange activity was assessed by monitoring pHi in cultured cells using the pH-sensitive dye, 2'7'-bis(carboxyethyl)-5(6)-carboxyfluorescein (BCECF). PDGF (60 ng/ml) exposure led to a marked activation of Na+/H+ exchange, evidenced by a rise in pHi (mean +/- SEM) of 0.20 +/- 0.03 pH units (n = 5, P < 0.05). EGF (60 ng/ml) exposure produced a rise in pHi of 0.27 +/- 0.03 pH units (n = 5, P < 0.05). Dimethyl amiloride (DMA, 50 microM), a competitive inhibitor of Na+/H+ exchange, blocked the pH response to PDGF and EGF. PA SMC showed a proliferative response when exposed to PDGF and EGF which was attenuated by 50 microM DMA (n = 6). Thus, activation of the Na+/H+ exchanger may be important in pulmonary cell signaling in response to growth factors as it has been found to be in systemic vessels.


Societal Costs and Outcomes of Medical and Recreational Marijuana Policies in the United States: A Systematic Review.
Significant support exists in the United States for legalization of marijuana/cannabis. As of 2021, 36 states and four territories approved the legalization of medical cannabis via medical marijuana laws (MMLs), and 15 states and District of Columbia (DC) have adopted recreational marijuana laws (RMLs). We performed structured and systematic searches of articles published from 2010 through September 2021. We assess the literature pertaining to adolescent marijuana use; opioid use and opioid-related outcomes; alcohol use; tobacco use; illicit and other drug use; marijuana growing and cultivation; employment, earnings, and other workplace outcomes; academic achievement and performance; criminal activity; perceived harmfulness; traffic and road safety; and suicide and sexual activity. Overall, 113 articles satisfied our inclusion criteria. Except for opioids, studies on use of other substances (illicit drugs, tobacco, and alcohol) were inconclusive. MMLs and RMLs do not generate negative outcomes in the labor market, lead to greater criminal activity, or reduce traffic and road safety.


Prognostic significance of early response to a single dose of asparaginase in childhood acute lymphoblastic leukemia.
The in vitro and in vivo efficacy of a single dose of asparaginase in children with newly diagnosed acute lymphoblastic leukemia and the correlation between in vitro and in vivo antileukemic response and long-term outcome were prospectively evaluated. Two hundred fifty-one patients were randomized to receive 1 of 3 asparaginase preparations (Escherichia coli, Erwinia chrysanthemi [Erwinia], or pegaspargase). In vitro assessment of efficacy was expressed as the percent total cell kill (TCK), based on the number of viable cells found after 5 days of culture in the presence of asparaginase. In vivo leukemia cell kill (LCK) was calculated by comparing bone marrow cellularity and percent leukemic blasts in marrow obtained before and 5 days after treatment with a single dose of asparaginase. Acute toxicity was determined by clinical and laboratory assessment. There was equivalent cell kill with all three types of asparaginase. The mean in vitro TCKs for E. coli, Erwinia, and pegaspargase were 31%, 39%, and 36%, respectively (P = 0.63). The mean LCKs in marrow of patients exposed to E. coli, Erwinia, and pegaspargase were 69%, 74%, and 65%, respectively (P = 0.88). The lack of response to asparaginase in vitro predicted a higher risk for clinical relapse regardless of risk assignment (12 leukemic events among 21 in vitro nonresponders; 57%, P < 0.001). There was no difference in acute toxicity among the three asparaginase preparations. All three asparaginase preparations produced equivalent LCKs in in vitro and in vivo analyses. In vitro response to asparaginase provided a risk group-independent prognostic factor.


Angle of Insertion and Torsional Resistance of Nickel-Titanium Rotary Instruments.
Previously published studies have investigated the influence of instrument access on cyclic fatigue resistance. However, no studies have evaluated the relationship between angulated access and torsional resistance. The aim of this study was to investigate the influence of the angle of access on the torsional resistance of endodontic instruments. One hundred and eighty instruments were selected: 90 F-One Blue 25/04 and 90 HeroShaper 25/04 instruments. Three subgroups (n = 30) for each instrument type (A and B) were established according to the angle of insertion of the instruments inside the artificial canal (0°, 10° and 20°). The tests were performed using a custom-made device consisting of the following: a motor that can record torque values of 0.1 s; interchangeable stainless-steel canals with different curvature (0°, 10° and 20°) that allow the instrument's angulated insertion and keep it flexed during testing procedures; and a vise used to secure the instrument at 3 mm from the tip. Torque limit was set to 5.5 Ncm, and each instrument was rotated at 500 rpm until fracture occurred. Torque to fracture (TtF) was registered by the endodontic motor, and the fragment length (FL) was measured with a digital caliper. Fractographic analysis was performed using a scanning electron microscopy (SEM) evaluation to confirm the cause of failure. TtF values and fragment length (FL) values were statistically analyzed using one-way analysis of variance (ANOVA) test and the Bonferroni correction for multiple comparisons across the groups with significance set to a 95% confidence level. Regarding the F-One Blue instruments, the results showed a higher TtF for group A3 (20°) than for group A1 (0°) and group A2 (10°), with a statistically significant difference between group A3 and the other two groups (p < 0.05), whereas no statistically significant difference was found between group A1 and group A2 (p > 0.05). Regarding the HeroShaper instrument, the results showed the highest TtF for group B3, with a statistically significant difference between the three subgroups B1, B2 and B3 (p < 0.05). The results showed that the torsional resistance increases as the angle of instrument access increases with a varying intensity, according to the crystallographic phase of the instrument selected.


Adrenal Vein Sampling With Gadolinium Contrast Medium in a Patient With Florid Primary Aldosteronism and Iodine Allergy.
We describe a 35-year-old woman who was allergic to iodine contrast medium and was diagnosed with primary aldosteronism (PA) based on functional confirmatory tests. She was suspected to have unilateral PA because of marked hypertension, spontaneous hypokalemia, high plasma aldosterone, reduced plasma renin activity, and a right hypodense adrenal tumor. She wanted to become pregnant and requested adrenalectomy instead of medical treatment with mineralocorticoid receptor antagonists. Localization of PA by adrenal vein sampling (AVS) was necessary, but angiography with iodine contrast medium was not possible because of her allergy. AVS was performed using gadolinium contrast agent (gadoterate meglumine) instead of iodine, in combination with computed tomography angiography (CTA). In AVS, before and after adrenocorticotropin (ACTH) loading, 12 blood samples were drawn from the right adrenal vein, left adrenal central vein, left adrenal common duct, left and right renal veins, and the lower inferior vena cava with only 5 mL of gadolinium medium. There were no complications during AVS. Examination revealed an elevated aldosterone/cortisol ratio on the right side, lateralized ratio of 7.4, and contralateral ratio of 0.76; the patient was diagnosed with right unilateral PA. She underwent right adrenalectomy and showed improvements in aldosterone level from 312.4 pg/mL to 83.0 pg/mL, potassium from 3.0 mEq/L to 3.9 mEq/L, and systolic blood pressure from 138 mm Hg to 117 mm Hg. In PA patients with iodine allergy, AVS can be performed safely and precisely using gadolinium contrast combined with CTA.


Modeling mRNA Translation With Ribosome Abortions.
We derive a deterministic mathematical model for the flow of ribosomes along a mRNA called the ribosome flow model with extended objects and abortions (RFMEOA). This model incorporates important cellular features such as every ribosome covers several codons and they may detach from various regions along the track due to more realistic biological situations including phenomena of ribosome-ribosome collisions. We prove that the ribosome density profile along the mRNA in the RFMEOA and in particular, the protein production rate converge to a unique steady-state. Simulations of the RFMEOA demonstrate a surprising result that an increase in the initiation rate may sometimes lead to a decrease in the production rate. We believe that this model could be helpful to provide insight into the effects of premature termination on the protein expression and be useful for understanding and re-engineering the translation process.


Effect of age and chronic obstructive pulmonary disease on the Breathalyzer estimation of blood alcohol level.
Twenty volunteers, 10 with chronic obstructive pulmonary disease (COPD) and 10 with no disease, ingested a vodka cocktail. Serial determinations of blood alcohol level (BAL) by gas-liquid chromatography and simultaneous Breathalyzer estimations of BAL were used to calculate blood:breath alcohol partition coefficients (PCs). Data from the present study were combined with data obtained in a previous study using identical methodology to examine the relationship between age and BAL estimation. It was found that the Breathalyzer significantly underestimated BAL as a function of age. It was hypothesized that the underestimation may be due to closing volume (CV) as the Breathalyzer samples end-expiratory breath.


Dynamic tracking of non-stationarity in human ECoG activity.
Modeling brain network dynamics is essential in understanding neural mechanisms and developing neurotechnologies such as closed-loop stimulation therapies for a wide range of neurological disorders. Brain network activity could have non-stationary and time-variant dynamics, especially when the subject's brain is monitored for a long period, e.g., using the electrocorticogram (ECoG). This non-stationarity makes the modeling of dynamics challenging. In our prior work, we developed a framework to identify time-invariant linear state-space models (SSMs) to describe both stationary spontaneous neural population dynamics and input-output (IO) neural dynamics in response to electrical stimulation. Here, we develop an adaptive identification algorithm that estimates time-variant SSMs to track possible non-stationarity in brain network dynamics. We apply the adaptive algorithm to track high-density human ECoG dynamics in three subjects over a long time-period. We find that the adaptive identification algorithm can estimate time-variant SSMs that significantly outperform time-invariant SSMs in all subjects. Our results demonstrate that non-stationary dynamics exist in high-dimensional human ECoG signals over long time-periods, and that the proposed adaptive SSM identification algorithm can successfully track these non-stationarities. These results have important implications for more accurate estimation of neural biomarkers for different brain states and for adaptive closed-loop stimulation therapy across a wide range of neurological disorders.


Participation in treatment decision-making by women with early stage breast cancer.
OBJECTIVE: This study aimed to assess the way women treated for early stage breast cancer perceived the treatment selection process. The purpose was to understand more fully patients' experiences of the decision process and their preferences for participation in treatment decisions. SETTING AND PARTICIPANTS: The study informants were 40 women, treated at a teaching hospital in Sydney Australia, who were interviewed face to face 1 year after their first treatment for stage I or stage II breast cancer. METHODS: This study used a qualitative approach, based on the analysis of interview transcripts. The main areas covered were how the informants' treatment decisions were made and their preferences for participation in treatment decisions. Content and thematic analyses were conducted with findings presented using verbatim quotations for illustration. RESULTS AND CONCLUSIONS: Many of the informants who preferred not to participate in decisions also failed to recognize the need for value judgements (as well as medical expertise) in the decision-making process. Some informants believed they ought to be responsible for the consequences whilst others did not. Difficulties were identified in patient utilization of medical information for treatment decision-making, and also in establishing preferences for the risks and benefits of treatments where few patients had prior experience of the potential outcomes. The findings indicate that patient participation in treatment decision-making is a more complex issue than simply giving patients information and choices. Ways of enhancing patients' involvement in the treatment selection process are discussed.


The Emerging Role of Amino Acid PET in Neuro-Oncology.
Imaging plays a critical role in the management of the highly complex and widely diverse central nervous system (CNS) malignancies in providing an accurate diagnosis, treatment planning, response assessment, prognosis, and surveillance. Contrast-enhanced magnetic resonance imaging (MRI) is the primary modality for CNS disease management due to its high contrast resolution, reasonable spatial resolution, and relatively low cost and risk. However, defining tumor response to radiation treatment and chemotherapy by contrast-enhanced MRI is often difficult due to various factors that can influence contrast agent distribution and perfusion, such as edema, necrosis, vascular alterations, and inflammation, leading to pseudoprogression and pseudoresponse assessments. Amino acid positron emission tomography (PET) is emerging as the method of resolving such equivocal lesion interpretations. Amino acid radiotracers can more specifically differentiate true tumor boundaries from equivocal lesions based on their specific and active uptake by the highly metabolic cellular component of CNS tumors. These therapy-induced metabolic changes detected by amino acid PET facilitate early treatment response assessments. Integrating amino acid PET in the management of CNS malignancies to complement MRI will significantly improve early therapy response assessment, treatment planning, and clinical trial design.


[Turner' syndrome (monosomy) and pregnancy].
Fertility in cases of 45-XO-Turner's syndrome is extremely rare. In cases with pregnancy, spontaneous abortions, stillborns and chromosomal defects are frequently diagnosed. We report on the unusual case of a now 36-year-old woman, who is to our knowledge the 25th case of monosomy X to achieve pregnancy, but is the first one to give birth to three healthy children.


Hereditary macrothrombocytopenia and pregnancy.
Hereditary macrothrombocytopenias (HM) are a group of infrequent disorders characterized by hereditary giant platelets. Little has been published about the course of these diseases during pregnancy and delivery. Forty consecutive thrombocytopenic pregnant women were studied. Platelet count, mean platelet volume and blood smear examination were performed. Platelet antibodies were studied by immunofluorescence. Familial study, bleeding time, ultrastructural platelet examination, a von Willebrand disease screening and aggregation tests were carried out when HM was suspected. Four cases of HM were diagnosed. Giant platelets were observed in all cases, with the typical ultrastructural pattern. Döhle-like cytoplasmic inclusions in granulocytes were observed in one case. Platelet antibodies were detected in only one case. No prophylactic measures to prevent haemorrhage were adopted, and all patients underwent vaginal deliveries. Haemorrhagic events were absent in both mothers and children. The prevalence of HM in pregnant trombocytopenic women is higher than assumed. Prophylactic treatment should be avoided in the absence of a history of haemorrhagic complications and obstetrical risk factors.


Aortic dissection in puerperium: a case report.
An acute type A aortic dissection, complicated by massive aortic regurgitation, was diagnosed in the case of a 32-year-old woman, thirty-three days post partum. Emergency operation (Cabrol II) was performed with an uneventful postoperative course. We draw attention to this high risk event, which is particularly apt to involve women within a short time after an otherwise uneventful pregnancy.


Association Between Diabetic Retinopathy and Cognitive Impairment: A Systematic Review and Meta-Analysis.
Diabetic retinopathy (DR) is one of the most common microvascular complications associated with diabetes mellitus. However, its correlation with another diabetes-related disorder, cognitive impairment, has not been well studied. This systematic review and meta-analysis aimed to explore the association between DR and cognitive impairment. MEDLINE (PubMed), the Cochrane Library, and EMBASE databases were searched for observational studies that reported an association between DR and cognitive impairment. Data from selected studies were extracted, and a meta-analysis was conducted using fixed-effects modeling. Fifteen observational studies were included in the systematic review, and 10 studies were included in the meta-analysis. The odds ratio of the association between DR and cognitive impairment was 2.24 (95% confidence interval [CI], 1.89-2.66; I 2 = 0.8%). The hazard ratio of the association between DR and cognitive impairment was significant in four studies, ranging from 1.09-1.32. Minimal or mild DR was not significantly associated with cognitive impairment (odds ratio [OR], 2.04; 95% CI, 0.87-4.77). However, the association between proliferative DR and cognitive impairment (OR, 3.57; 95% CI, 1.79-7.12; I 2 = 16.6%) was not stronger than the association between moderate or worse DR and cognitive impairment (OR, 4.26; 95% CI, 2.01-9.07; I 2 = 0.0%). DR is associated with cognitive impairment, and screening for DR will be helpful for the early identification of individuals with cognitive impairment. Further studies are needed to confirm the association between proliferative DR and cognitive impairment.


Water-soluble ruthenium(II) catalysts [RuCl2(eta6-arene)[P(CH2OH)3]] for isomerization of allylic alcohols and alkyne hydration.
The novel water-soluble ruthenium(II) complexes [RuCl(2)(eta(6)-arene)[P(CH(2)OH)(3)]]2a-c and [RuCl(eta(6)-arene)[P(CH(2)OH)(3)](2)][Cl]3a-c have been prepared in high yields by reaction of dimers [[Ru(eta(6)-arene)(micro-Cl)Cl](2)](arene = C(6)H(6)1a, p-cymene 1b, C(6)Me(6)1c) with two or four equivalents of P(CH(2)OH)(3), respectively. Complexes 2/3a-c are active catalysts in the redox isomerization of several allylic alcohols into the corresponding saturated carbonyl compounds under water/n-heptane biphasic conditions. Among them, the neutral derivatives [RuCl(2)(eta(6)-C(6)H(6))[P(CH(2)OH)(3)]]2a and [RuCl(2)(eta(6)-p-cymene)[P(CH(2)OH)(3)]]2b show the highest activities (TOF values up to 600 h(-1); TON values up to 782). Complexes 2/3a-c also catalyze the hydration of terminal alkynes.


Brain transcriptomes of zebrafish and mouse Alzheimer's disease knock-in models imply early disrupted energy metabolism.
Energy production is the most fundamentally important cellular activity supporting all other functions, particularly in highly active organs, such as brains. Here, we summarise transcriptome analyses of young adult (pre-disease) brains from a collection of 11 early-onset familial Alzheimer's disease (EOFAD)-like and non-EOFAD-like mutations in three zebrafish genes. The one cellular activity consistently predicted as affected by only the EOFAD-like mutations is oxidative phosphorylation, which produces most of the energy of the brain. All the mutations were predicted to affect protein synthesis. We extended our analysis to knock-in mouse models of APOE alleles and found the same effect for the late onset Alzheimer's disease risk allele ε4. Our results support a common molecular basis for the initiation of the pathological processes leading to both early and late onset forms of Alzheimer's disease, and illustrate the utility of zebrafish and knock-in single EOFAD mutation models for understanding the causes of this disease.


A novel scoring function for discriminating hyperthermophilic and mesophilic proteins with application to predicting relative thermostability of protein mutants.
The ability to design thermostable proteins is theoretically important and practically useful. Robust and accurate algorithms, however, remain elusive. One critical problem is the lack of reliable methods to estimate the relative thermostability of possible mutants. We report a novel scoring function for discriminating hyperthermophilic and mesophilic proteins with application to predicting the relative thermostability of protein mutants. The scoring function was developed based on an elaborate analysis of a set of features calculated or predicted from 540 pairs of hyperthermophilic and mesophilic protein ortholog sequences. It was constructed by a linear combination of ten important features identified by a feature ranking procedure based on the random forest classification algorithm. The weights of these features in the scoring function were fitted by a hill-climbing algorithm. This scoring function has shown an excellent ability to discriminate hyperthermophilic from mesophilic sequences. The prediction accuracies reached 98.9% and 97.3% in discriminating orthologous pairs in training and the holdout testing datasets, respectively. Moreover, the scoring function can distinguish non-homologous sequences with an accuracy of 88.4%. Additional blind tests using two datasets of experimentally investigated mutations demonstrated that the scoring function can be used to predict the relative thermostability of proteins and their mutants at very high accuracies (92.9% and 94.4%). We also developed an amino acid substitution preference matrix between mesophilic and hyperthermophilic proteins, which may be useful in designing more thermostable proteins. We have presented a novel scoring function which can distinguish not only HP/MP ortholog pairs, but also non-homologous pairs at high accuracies. Most importantly, it can be used to accurately predict the relative stability of proteins and their mutants, as demonstrated in two blind tests. In addition, the residue substitution preference matrix assembled in this study may reflect the thermal adaptation induced substitution biases. A web server implementing the scoring function and the dataset used in this study are freely available at http://www.abl.ku.edu/thermorank/.


Consolidated and distributed nap schedules and performance.
This study compared alertness and psychomotor performance over an extended work period in which participants received either a 4-h afternoon nap or four 1-h naps during the night. It was hypothesized that alertness and performance would be superior during the night following the 4-h afternoon nap and that the overall level of performance would be related to the amount of sleep obtained. It was found that when a series of 1-h naps was taken during the normal night period, oral temperature and psychomotor performance also declined. However, performance was relatively improved on the following evening. In contrast, with an effective 4-h prophylactic nap, performance remained near baseline levels across the night. It was concluded that the placement of sleep periods during extended work be based on knowledge of when maximal performance would be required.


The use of the Internet by gay and bisexual male escorts: sex workers as sex educators.
While prior studies have targeted street-based male sex workers as potential vectors of disease transmission, the number of men who work independently through Internet chat-rooms and other online endeavors has steadily increased. It is likely that these men differ substantially from their street-based counterparts in terms of sexual risk behaviors with their clients. The purpose of this study was to explore the ways in which the Internet has impacted the work of male escorts and their sexual practices with clients. Semi-structured qualitative interviews and quantitative surveys were administered to 46 such men. Less than half the men reported unprotected anal sex with clients. The qualitative data lend support to this finding, in that the majority talked about refusing any unsafe sex with clients, and many reported taking the extra step of educating their clients about the dangers of risky sex. Some of the escorts described the methods used to incorporate safer sex practices into sessions with their clients. Internet-based male escorts can play an important role as potential sex educators on the front lines of the fight against HIV and other sexually transmitted infections.


Identification of differentially expressed genes in the pheromone glands of mated and virgin Bombyx mori by digital gene expression profiling.
Mating decreases female receptivity and terminates sex pheromone production in moths. Although significant progress has been made in elucidating the mating-regulated inactivation of pheromone biosynthesis-activating neuropeptide (PBAN) secretion, little is known about the mating induced gene expression profiles in pheromone glands (PGs). In this study, the associated genes involved in Bombyx mori mating were identified through digital gene expression (DGE) profiling and subsequent RNA interference (RNAi) to elucidate the molecular mechanisms underlying the mating-regulated gene expression in PGs. Eight DGE libraries were constructed from the PGs of mated and virgin females: 1 h mating (M1)/virgin (V1) PGs, 3 h mating (M3)/virgin (V3) PGs, 24 h mating (M24)/virgin (V24) PGs and 48 h mating (M48)/virgin (V48) PGs (M48 and V48). These libraries were used to investigate the gene expression profiles affected by mating. DGE profiling revealed a series of genes showing differential expression in each set of mated and virgin female samples, including immune-associated genes, sex pheromone synthesis-associated genes, juvenile hormone (JH) signal-associated genes, etc. Most interestingly, JH signal was found to be activated by mating. Application of the JH mimics, methoprene to the newly-emerged virgin females leaded to the significant reduction of sex pheromone production. RNAi-mediated knockdown of putative JH receptor gene, Methoprene tolerant 1 (Met1), in female pupa resulted in a significant decrease in sex pheromone production in mature females, suggesting the importance of JH in sex pheromone synthesis. A series of differentially expressed genes in PGs in response to mating was identified. This study improves our understanding of the role of JH signaling on the mating-elicited termination of sex pheromone production.


Direct or Indirect Surgical Approach of Zygomatic Complex Fracture: A Comparative Study.
Zygoma is considered the main support of the midface. Zygoma is frequently fractured owing to its prominent site on the face. Treatment of zygomaticomaxillary complex fractures can be performed through either conservative or surgical measures (closed or open reduction). The study was a cross-sectional retrospective observational investigation done at 4 hospitals in Ramadi and Baghdad cities, Iraq. This investigation covered a duration of 6 years (2016-2021). We reviewed the medical records of patients with ZCFs. The participants were divided into 2 groups according to the approach used for their management (direct versus indirect approach). Data regarding the demographic and clinical characteristics were recorded for each subject. Of 265 patients with ZCFs, 209 (78.9%) were males. The highest age group affected was 18 to 40 years (51.7%). The majority of the ZCFs were caused by road traffic accidents (31.7%). Most of the cases belong to single fractures (72.1%). Cheek flattening (73.6%) was the commonest sign of the ZCFs. The majority of the fractures were treated by direct approach, 65.4% of the isolated fractures and 62.2% for multiple fractures. Excellent patient satisfaction was seen in the majority of the cases. There were no statistically significant differences between the 2 approaches regarding the abovementioned variables ( P -value > 0.05). The majority of the cases were with excellent patient satisfaction (n = 149) while only 7 patients with poor satisfaction. The age groups below 18 years and 18 to 40 years were associated with excellent patient satisfaction than good and poor satisfaction. All (n = 7) of the cases with poor satisfaction belong to the age group above 40 years. The majority of male (n = 113) and female (n = 36) patients were with excellent satisfaction, while all patients with poor results were males (n = 7). There were statistically significant differences between the results of the patient satisfaction and age group and complications ( P -value < 0.05). The ophthalmic complications were the most complications seen after ZCF surgical treatment (2.56%). Direct and indirect approaches can be used safely in the treatment of ZCFs owing to excellent patient satisfaction in the majority of the cases and a low complication rate. This study aims to evaluate the demographic and clinical characteristics and to compare different surgical procedures to treat patients with zygomaticomaxillary complex fractures in a country overwhelmed by violence.


Construction of the Interaction Network of Hub Genes in the Progression of Barrett's Esophagus to Esophageal Adenocarcinoma.
Esophageal adenocarcinoma (EAC) is one of the histologic types of esophageal cancer with a poor prognosis. The majority of EAC originate from Barrett's esophagus (BE). There are few studies focusing on the dynamic progression of BE to EAC. R software was used to analyze differentially expressed genes (DEGs) based on RNA-seq data of 94 normal esophageal squamous epithelial (NE) tissues, 113 BE tissues and 147 EAC tissues. The overlapping genes of DEGs between BE and EAC were analyzed by Venn diagram tool. The hub genes were selected by Cytoscape software based on the protein-protein interaction network of the overlapping genes using STRING database. The functional analysis of hub genes was performed by R software and the protein expression was identified by immunohistochemistry. In the present study, we found a large degree of genetic similarity between BE and EAC, and further identified seven hub genes (including COL1A1, TGFBI, MMP1, COL4A1, NID2, MMP12, CXCL1) which were all progressively upregulated in the progression of NE-BE-EAC. We have preliminarily uncovered the probable molecular mechanisms of these hub genes in disease development and constructed the ceRNA regulatory network of hub genes. More importantly, we explored the possibility of hub genes as biomarkers in the disease progression of NE-BE-EAC. For example, TGFBI can be used as biomarkers to predict the prognosis of EAC patients. COL1A1, NID2 and COL4A1 can be used as biomarkers to predict the response to immune checkpoint blockade (ICB) therapy. We also constructed a disease progression risk model for NE-BE-EAC based on CXCL1, MMP1 and TGFBI. Finally, the results of drug sensitivity analysis based on hub genes showed that drugs such as PI3K inhibitor TGX221, bleomycin, PKC inhibitor Midostaurin, Bcr-Abl inhibitor Dasatinib, HSP90 inhibitor 17-AAG, and Docetaxel may be potential candidates to inhibit the progression of BE to EAC. This study is based on a large number of clinical samples with high credibility, which is useful for revealing the probable carcinogenic mechanism of BE to EAC and developing new clinical treatment strategies.


Squamous cell carcinoma of submandibular salivary gland: A rare case report.
Malignant tumors of submandibular salivary gland are rare in occurrence. Squamous cell carcinoma of salivary glands accounts for about 0.9-4.7% of all salivary gland tumors with a predilection to occur in parotid gland due to perinodal involvement. Primary squamous cell carcinoma of submandibular salivary gland accounts to about 2% of the tumors and hence it is being represented for its rarity.


Establishing the epigenetic status of the Prader-Willi/Angelman imprinting center in the gametes and embryo.
The Prader-Willi/Angelman imprinted domain on human chromosome 15q11-q13 is regulated by an imprinting control center (IC) composed of a sequence around the SNRPN promoter (PWS-SRO) and a sequence located 35 kb upstream (AS-SRO). We have previously hypothesized that the primary imprint is established on AS-SRO, which then confers imprinting on PWS-SRO. Here we examine this hypothesis using a transgene that includes both AS-SRO and PWS-SRO sequences and carries out the entire imprinting process. The epigenetic features of this transgene resemble those previously observed on the endogenous locus, thus allowing analyses in the gametes and early embryo. We demonstrate that the primary imprint is in fact established in the gametes, creating a differentially methylated CpG cluster (DMR) on AS-SRO, presumably by an adjacent de novo signal (DNS). The DMR and DNS bind specific proteins: an allele-discrimination protein (ADP) and a de novo methylation protein, respectively. ADP, being a maternal protein, is involved in both the establishment of DMR in the gametes and in its maintenance through implantation when methylation of PWS-SRO on the maternal allele takes place. Importantly, while the AS-SRO is required in the gametes to confer methylation on PWS-SRO, it is dispensable later in development.


Exploring the use of machine learning for the assessment of skeletal fracture morphology and differentiation between impact mechanisms: A pilot study.
Analyzing and interpreting traumatic injuries is a fundamental aspect of routine forensic case work. As the human skeleton can be impacted through a combination of loading mechanisms and varying impact energies, the analysis and interpretation of skeletal trauma can be complex. Therefore, it is imperative that the reliability of techniques used for analysis are well-established. There is growing interest in machine learning (ML) in medicine (especially radiology) regarding the use of image classification (a subset of ML) to categorize and predict classes of medical images. Therefore, the feasibility of using image classification for skeletal trauma analysis should be explored for its benefits to forensic pathology and anthropology. The method explored in this paper examined the potential for machine learning, using three dimensional (3D) convolutional neural networks (CNNs), to assess whether morphological features of skeletal trauma to the femur can be used to differentiate between impact mechanisms within a forensic population. The objective of this study was to assess if morphological differences in femoral fractures seen in post-mortem-computed tomographic images (PMCT) could be categorized according to mechanism, specifically horizontal impacts resulting from pedestrian motor vehicle impacts (PMVIs) and vertical impact s resulting from high impact falls. Final model results indicated an accuracy between 69.95%-72.86% and 63.08%-66.24% validation. Although these results mean the method could not be practically used in its current form, as a proof of concept, there is potential for it to be developed as a tool to assist in classifying complex fracture states.


Distribution of Lower Limb Spasticity Does Not Influence Mobility Outcome Following Traumatic Brain Injury: An Observational Study.
To examine the association between lower limb spasticity and mobility limitations following traumatic brain injury (TBI) and determine the influence of spasticity distribution on mobility outcomes following TBI. A large metropolitan rehabilitation hospital. Ninety-three ambulant people with TBI who were attending physiotherapy for mobility limitations. Cross-sectional cohort study. The High-Level Mobility Assessment Tool, gait velocity, and the Tardieu scale. Lower limb spasticity was common following TBI, with a distal distribution being the most prevalent. Participants with spasticity had significantly greater initial mobility limitations than participants without spasticity. However, the distribution of lower limb spasticity and the presence of unilateral or bilateral spasticity had no additional impact on mobility outcomes. There was no significant difference in mobility outcomes at the 6-month follow-up for people with spasticity, indicating that individuals have equivalent ability to improve their mobility over time despite the presence of spasticity. Following TBI, people with lower limb spasticity have significantly greater mobility limitations than those without spasticity, yet the presence and distribution of spasticity does not appear to impact mobility outcomes. There is long-term potential to improve mobility despite the presence of spasticity.


Marginal and joint distributions of S100, HMB-45, and Melan-A across a large series of cutaneous melanomas.
The distribution of the standard melanoma antibodies S100, HMB-45, and Melan-A has been extensively studied. Yet, the overlap in their expression is less well characterized. To determine the joint distributions of the classic melanoma markers and to determine if classification according to joint antigen expression has prognostic relevance. S100, HMB-45, and Melan-A were assayed by immunofluorescence-based immunohistochemistry on a large tissue microarray of 212 cutaneous melanoma primary tumors and 341 metastases. Positive expression for each antigen required display of immunoreactivity for at least 25% of melanoma cells. Marginal and joint distributions were determined across all markers. Bivariate associations with established clinicopathologic covariates and melanoma-specific survival analyses were conducted. Of 322 assayable melanomas, 295 (91.6%), 203 (63.0%), and 236 (73.3%) stained with S100, HMB-45, and Melan-A, respectively. Twenty-seven melanomas, representing a diverse set of histopathologic profiles, were S100 negative. Coexpression of all 3 antibodies was observed in 160 melanomas (49.7%). Intensity of endogenous melanin pigment did not confound immunolabeling. Among primary tumors, associations with clinicopathologic parameters revealed a significant relationship only between HMB-45 and microsatellitosis (P = .02). No significant differences among clinicopathologic criteria were observed across the HMB-45/Melan-A joint distribution categories. Neither marginal HMB-45 (P = .56) nor Melan-A (P = .81), or their joint distributions (P = .88), was associated with melanoma-specific survival. Comprehensive characterization of the marginal and joint distributions for S100, HMB-45, and Melan-A across a large series of cutaneous melanomas revealed diversity of expression across this group of antigens. However, these immunohistochemically defined subclasses of melanomas do not significantly differ according to clinicopathologic correlates or outcome.


Efficient tools for marine operational forecast and oil spill tracking.
Ocean forecasting and oil spill modelling and tracking are complex activities requiring specialised institutions. In this work we present a lighter solution based on the Operational Ocean Forecast Python Engine (OOFε) and the oil spill model General NOAA Operational Modelling Environment (GNOME). These two are robust relocatable and simple to implement and maintain. Implementations of the operational engine in three different regions with distinct oceanic systems, using the ocean model Regional Ocean Modelling System (ROMS), are described, namely the Galician region, the southeastern Brazilian waters and the Texas-Louisiana shelf. GNOME was able to simulate the fate of the Prestige oil spill (Galicia) and compared well with observations of the Krimsk accident (Texas). Scenarios of hypothetical spills in Campos Basin (Brazil) are illustrated, evidencing the sensitiveness to the dynamical system. OOFε and GNOME are proved to be valuable, efficient and low cost tools and can be seen as an intermediate stage towards more complex operational implementations of ocean forecasting and oil spill modelling strategies.


Access to Pediatric Eye Care Following Vision Screening.
To quantify the accessibility of eye care providers from photoscreening centers within the vision screening region in relation to population density and median household income. Driving times between vision screening locations and eye care centers were mapped and analyzed using OpenStreetMap software (Open Street Map Foundation). U.S. Census Bureau data of population density and median household income were linked with screening centers using ArcGIS Online (Esri) to determine correlations with driving times. A total of 290 driving times for 145 photo-screening centers, 147 optometrists, and 7 pediatric ophthalmologists were calculated and mapped. Median driving times from a photoscreening center to the nearest optometrist and ophthalmologist were 4.74 and 25.10 minutes, respectively, with 90% of the screening centers residing within 12.46 and 67.19 minutes of the nearest optometrist and ophthalmologist, respectively. Driving times to optometrists are far less than times to pediatric ophthalmologists due to the greater number of optometrists. Decreasing driving times with increasing population and median household income indicate the concentration of optometrists and pediatric ophthalmologists within urbanized areas. Most photoscreening centers reside within 5 and 70 minutes of the nearest optometrist and pediatric ophthalmologist, respectively. Driving times indicate the region's greater accessibility to optometrists than to pediatric ophthalmologists. Eye care centers tend to be localized within urbanized areas with higher population densities and higher median household incomes. [J Pediatr Ophthalmol Strabismus. 2022;59(6):369-374.].


Thyrotropin and thyroid antibodies as predictors of hypothyroidism: a 13-year, longitudinal study of a community-based cohort using current immunoassay techniques.
Longitudinal studies of risk factors for hypothyroidism are required to inform debate regarding the TSH reference range. There are limited longitudinal data on the predictive value of thyroid antibodies measured by automated immunoassay (as opposed to semiquantitative methods). We measured TSH, free T(4), thyroid peroxidase antibodies (TPOAbs), and thyroglobulin antibodies (TgAbs) using the Immulite platform on sera from 1184 participants in the 1981 and 1994 Busselton Health Surveys. Outcome measures at follow-up were hypothyroidism, defined as TSH greater than 4.0 mU/liter or on thyroxine treatment; and overt hypothyroidism, defined as TSH above 10.0 mU/liter or on thyroxine treatment. Receiver-operator characteristic analysis was used to determine optimal cutoffs for baseline TSH, TPOAbs, and TgAbs as predictors of hypothyroidism. At 13 yr follow-up, 110 subjects (84 women) had hypothyroidism, of whom 42 (38 women) had overt hypothyroidism. Optimal cutoffs for predicting hypothyroidism were baseline TSH above 2.5 mU/liter, TPOAbs above 29 kIU/liter, and TgAbs above 22 kIU/liter, compared with reference range upper limits of 4.0 mU/liter, 35 kIU/liter, and 55 kIU/liter, respectively. In women with positive thyroid antibodies (TPOAbs or TgAbs), the prevalence of hypothyroidism at follow-up (with 95% confidence intervals) was 12.0% (3.0-21.0%) when baseline TSH was 2.5 mU/liter or less, 55.2% (37.1-73.3%) for TSH between 2.5 and 4.0 mU/liter, and 85.7% (74.1-97.3%) for TSH above 4.0 mU/liter. The use of TSH cutoffs of 2.5 and 4.0 mU/liter, combined with thyroid antibodies, provides a clinically useful estimate of the long-term risk of hypothyroidism.


Breast milk donation and social support: reports of women donors.
The study aimed to characterize the behavior of human milk donation and to describe the informal social and formal institutional support, according to reports from women donors. It is an exploratory, cross-sectional, descriptive study using domicile interviews based on structured and semi-structured scripts. The participants were 36 women enrolled in two human milk banks of the public health system of the Federal District. Statistical analysis of quantitative data and categorical content analysis of qualitative data were performed. Categories of reasons that most influenced the frequency of expressing were: food, time availability, negative emotions and fluid intake. The manual expressing technique was reported as predominant. The use of breast shells was cited by almost a third of the donors. Most frequent suggestions for improving institutional support were more attention and support from the milk banks for the donor. The study may serve as a stimulus for the implementation of technical and political strategies to encourage this practice.


Evaluation of the impact of subepithelial corneal infiltrates on corneal biomechanics after epidemic keratoconjunctivitis.
To examine the effect of subepithelial corneal infiltrates on corneal biomechanical properties after epidemic keratoconjunctivitis compared to that in healthy controls. The cross-sectional study included consecutive patients with bilateral subepithelial corneal infiltrates after epidemic keratoconjunctivitis and healthy controls. Best corrected visual acuity corneal subepithelial infiltrate scoring Fantes grading scale, and central corneal thickness were measured. Corneal hysteresis corneal resistance factor Goldmann correlated intraocular pressure and corneal compensated intraocular pressure were assessed using an ocular response analyzer. This study included 66 eyes of 33 patients with subepithelial corneal infiltrates following epidemic keratoconjunctivitis and randomly selected 37 eyes of 37 healthy volunteers. The mean Fantes and CSIS scores were 1.8 ± 0.8 and 2.9 ± 1.3, respectively, in the first involved eyes and 1.3 ± 1.1 and 1.9 ± 1.7, respectively, in the fellow eyes (p=0.009 and p=0.002, respectively). The first (526.1 ± 28.1 µm; p=0.005) and second involved eyes (523.4 ± 38.1 µm; p=0.044) had significantly thinner corneas compared to that in healthy controls (557.0 ± 38.1 µm). While best-corrected visual acuity showed a positive correlation with corneal resistance factor (r=0.363, p=0.045) and corneal hysteresis (r=0.414, p=0.021), corneal subepithelial infiltrate scoring showed a negative correlation with Goldmann correlated intraocular pressure (r=-0.479, p=0.006) and corneal compensated intraocular pressure (r=-0.413, p=0.021). Eyes with subepithelial corneal infiltrates had significantly thinner corneas compared to that in healthy controls. A positive correlation of the corneal resistance factor and corneal hysteresis with best-corrected visual acuity and a negative correlation of the Goldmann correlated intraocular pressure and corneal compensated intraocular pressure with corneal subepithelial infiltrate scoring should be taken into account when measuring intraocular pressure values in patients with subepithelial corneal infiltrates.


Transcapillary fluid balance consequences of missing initial lymphatics studied in a mouse model of primary lymphoedema.
To investigate the phenotypic consequences of a deranged lymphangiogenesis in relation to tissue fluid accumulation and the possible role of inflammation in the pathogenesis of lymphoedema, we measured determinants of transcapillary fluid filtration and inflammatory mediators in the interstitial fluid in genetically engineered Chy mice, a model for primary congenital lymphoedema (Milroy's disease). Although initial lymphatics were not present in dermis in any of the areas studied (fore paw, hind paw, thigh and back skin) interstitial fluid pressure (P(if)), measured with micropipettes, and tissue fluid volumes were significantly increased only in the areas with visible swelling - the fore and hind paw, whereas interstitial colloid osmotic pressure (COP(if)) was increased in all the skin areas examined. A volume load of 15% of body weight resulted in a more pronounced increase in P(if) as well as a four-fold increase in interstitial fluid volume in Chy relative to wild-type (wt) mice, showing the quantitative importance of lymphatics for fluid homeostasis during acute perturbations. A similar level of proinflammatory markers in interstitial fluid in early established lymphoedema (3-4 months) in Chy and wt suggests that inflammation does not have a major pathogenetic role for the development of lymphoedema, whereas a reduced level of the immunomodulatory cytokine interleukin (IL)-4 may result in a reduced immunological defence ability and thus lead to the increase in inflammatory cytokines IL-2 and IL-6 observed at a later stage (11-13 months). Our data suggest that primary lymphoedema results in a high interstitial fluid protein concentration that does not induce an interstitial inflammatory reaction per se, and furthermore shows the paramount importance of the initial lymphatics in tissue fluid homeostasis, especially during perturbations of transcapillary fluid balance.


Strain-specific responses of inbred mice to ethanol following food shortage.
Specific inbred mouse strains such as C57BL/6J and DBA/2J show differences in consumption of and reaction on drugs of abuse. For example, C57BL/6J mice voluntarily consume greater amounts of ethanol than DBA/2J mice. Recently, it could be shown that a short environmental experience--12 days of food shortage followed by a recovery period--has a strong impact on strain-specific reactions to amphetamine. The purpose of the present study was to examine whether food shortage experience has an effect on ethanol responses. The effect of a period of 12 days food restriction which resulted in a weight loss of 20% body weight and which was followed by a complete recovery period was studied on ethanol self-administration and ethanol-induced locomotor activity in C57BL/6Ico and DBA/2Ico inbred mouse strains. The experience of food shortage led to a higher ethanol intake and preference in C57BL/6Ico mice compared to control animals without food shortage experience. In contrast DBA/2Ico showed no difference in ethanol intake or preference following this experience. The effect of ethanol onto locomotor activity of both mice strains was affected only in the case of DBA/2Ico mice, where food shortage experience resulted in a significantly higher ethanol-induced locomotor activity. The present data show that in inbred mouse strains environmental experiences can have a strong impact onto the effects of ethanol. In conclusion, in the field of preclinical alcohol research gene x environment interactions in specific inbred mouse strains can contribute strongly to the outcome of studies and more specifically food shortage can profoundly affect the outcome of alcohol studies in mice.


Possible Impact of 190G > A CCR2 and Δ32 CCR5 Mutations on Decrease of the HBV Vaccine Immunogenicity-A Preliminary Report.
Background: Chemokine genetic variations are involved in infectious diseases such as hepatitis B virus (HBV). Several allelic variants might, in theory, affect the outcome of vaccination. Objectives: This study was carried out to examine the associations of Δ32 CCR5 and 190G > A CCR2 polymorphisms with a response to a primary course of three HBV vaccinations. Methods: Between December 2014 and December 2016, patients from three randomly selected primary care clinics in the West Pomeranian region (Poland), 1 month after receiving the third dose of HBV vaccine, were enrolled. Enzyme-linked immunosorbent assay (ELISA) system version 3.0 was used to detect anti-HBs and anti-HBc totals. The identification of polymorphisms were performed by a polymerase chain reaction technique using a single primer extension assay. Genotype distributions of responders versus non-responders to HBV vaccination were compared on the basis of anti-HBs level. Results: In 149 patients (mean age 60 years) the mean anti-HBs level was 652.2 ± 425.9 mIU/mL (range: 0-1111.0 mIU/mL). There were 14.1% (n = 21) non-responders to the HBV vaccine (anti-HBs < 10.0 mIU/mL). The wild type/Δ32 genotype of CCR5 gene was found in 18.1% participants, and 1.3% were Δ32/Δ32 homozygotes. The frequency of allele A of the CCR2 gene was 11.1%. Lower anti-HBs levels in Δ32/Δ32 homozygotes were observed (Me = 61 mIU/mL vs. Me = 660.2 mIU/mL; p = 0.048). As age was found to be a correlate to the anti-HBs titer (r = -0.218, p = 0.0075; 95% CI: -0.366--0.059)-an analysis of a co-variance was performed which found a statistically significant (p = 0.04) difference in anti-HBs titres between Δ32/Δ32 homozygotes and other CCR5 genotypes. The association between anti-HBs titres and CCR2 genotypes was not statistically significant. Conclusions: Our study-which is a preliminary report that suggest this topic deserves further observation with larger sample sizes, different ethnicities, and other single nucleotide poly-morphisms (SNPs)-suggests the possible involvement of CCR5 polymorphism in impairing the immunologic response to HBV vaccination, predominantly in relation to the passage of time.


[The duplex sonographic diagnosis of portal hypertension in liver cirrhosis. The effect of a standardized test meal on portal hemodynamics].
The effect of a standardized test meal on portal haemodynamics was measured by duplex ultrasonography in healthy subjects (12 men and 13 women; mean age 43 +/- 9 years) and patients with liver cirrhosis (14 men and 11 women; mean age 55 +/- 10 years). Maximal flow velocity, vessel diameter and flow volume were measured in the portal vein and superior mesenteric artery before the test meal and 15, 30 and 45 min thereafter. After a 12-hour fasting period maximal flow velocity in the portal vein was significantly lower in the cirrhosis patients than the normal subjects (P less than 0.05), but the individual values clearly overlapped. 30 min after the test meal flow velocity in the portal vein rose by 22%, flow volume by 29% in the cirrhosis patients, but by 76% and 131%, respectively, in the normal controls (P less than 0.01). Vessel diameter remained constant in the patients, but increased significantly in the controls (P less than 0.05). There was no overlapping of values between the two groups. The increase in flow velocity in the superior mesenteric artery was nearly the same in both groups. It is concluded that, after a test meal the haemodynamic differences between normal subjects and cirrhosis patients becomes quite marked and thus can provide a more exact diagnosis of portal hypertension by duplex ultrasonography.


Corneal biomechanics, optic disc morphology, and macular ganglion cell complex in myopia.
To determine the association between corneal biomechanical properties and optic disc morphology, to verify the relationship between corneal biomechanical properties and peripapillary retinal nerve fiber layer (pRNFL) thickness in myopia, and to investigate the association between axial length (AL) and pRNFL and macular inner retinal layer (MIRL) thickness in myopia. An observational cohort study was conducted. Corneal hysteresis (CH), corneal resistance factor, central corneal thickness (CCT), AL, MIRL thickness, and pRNFL thicknesses were measured. This study examined 100 eyes from 50 patients, age 33.48±8.32 years (mean±SD), with spherical equivalent ≤3 D. A multivariable mixed-model analysis adjusted by age and sex showed that CCT correlated negatively with disc area (P=0.002), rim area (P=0.007), cup area (P=0.01), cup/disc ratio (P=0.02), and cup volume (P=0.01). CH correlated negatively with disc area (P=0.03) and cup area (P=0.04). Neither CCT nor CH was correlated with pRNFL or MIRL. AL correlated negatively with the mean pRNFL (P=0.003), superior pRNFL (P=0.018), superiortemporal pRNFL (P=0.02), inferior pRNFL (P=0.033), and inferiornasal pRNFL (P=0.02), but not with MIRL. CCT and CH varied with optic disc morphology, but not with pRNFL or MIRL, in myopia. This relationship may relate to glaucoma risk in myopia. AL varied with pRNFL, primarily at the superior and inferior poles, but not with MIRL in myopia.


Near-infrared spectroscopy in head and neck surgery.
Near-infrared spectroscopy is commonly used during carotid endarterectomy but its use in salvage oncological carotid resection has not previously been described. In comparison to other methods of determining the adequacy of contralateral cerebral circulation, near-infrared spectroscopy is simple, reliable, non-invasive and inexpensive.


Integrated quantum photonic sensor based on Hong-Ou-Mandel interference.
Photonic-crystal-based integrated optical systems have been used for a broad range of sensing applications with great success. This has been motivated by several advantages such as high sensitivity, miniaturization, remote sensing, selectivity and stability. Many photonic crystal sensors have been proposed with various fabrication designs that result in improved optical properties. In parallel, integrated optical systems are being pursued as a platform for photonic quantum information processing using linear optics and Fock states. Here we propose a novel integrated Fock state optical sensor architecture that can be used for force, refractive index and possibly local temperature detection. In this scheme, two coupled cavities behave as an "effective beam splitter". The sensor works based on fourth order interference (the Hong-Ou-Mandel effect) and requires a sequence of single photon pulses and consequently has low pulse power. Changes in the parameter to be measured induce variations in the effective beam splitter reflectivity and result in changes to the visibility of interference. We demonstrate this generic scheme in coupled L3 photonic crystal cavities as an example and find that this system, which only relies on photon coincidence detection and does not need any spectral resolution, can estimate forces as small as 10(-7) Newtons and can measure one part per million change in refractive index using a very low input power of 10(-10)W. Thus linear optical quantum photonic architectures can achieve comparable sensor performance to semiclassical devices.


SNF5 is Involved in Suppression of Hepatocellular Carcinoma Progression via TGF-Beta 1 Signaling.
SNF5 (SMARCB1/INI1/BAF47), a core subunit of SWI/SNF complex, has been reported to modulate cell proliferation and apoptosis. Genetic evidence has suggested that SNF5 participates in tumor suppression. However, the detailed biological function and underlying mechanisms of SNF5 in hepatocellular carcinoma (HCC) progression remain unclear. Here, SNF5 expression reduction in HCC tissues compared with the adjacent non-cancerous tissues has been demonstrated. Importantly, the results showed that reduced SNF5 expression has a strong correlation with worse overall survival of HCC patients. The data demonstrated that knockdown of SNF5 significantly promoted cell growth and migration in Hep3B and HCCLM3 cell lines. Interestingly, it was found that SNF5 suppressed transforming growth factor-β1 (TGF-β1) expression, and SNF5 mRNA expression was negatively correlated with TGF-β1 in HCC tissues. Furthermore, depletion of SNF5 attenuated the sensitivity of HCC cells to sorafenib. Thus, the data suggested that SNF5 may participate in HCC suppression, and reduced expression of SNF5 correlates with the poor differentiation and prognosis of HCC, indicating that SNF5 might be an important prognostic biomarker and promising therapeutic target for HCC. Anat Rec, 299:869-877, 2016. © 2016 Wiley Periodicals, Inc.


Construction, purification and characterization of a recombinant baculovirus containing the gene for alpha subunit of human chorionic gonadotropin.
A cDNA encoding the alpha subunit of human chorionic gonadotropin, a placental glycoprotein hormone, was cloned downstream to the viral polyhedrin gene promoter of Autographa california nuclear polyhedrosis virus and the recombinant transfer vector was used to co-transfect Spodoptera frugiperda cells growing in culture. Recombinant baculovirus carrying the alpha hCG gene was detected and isolated after dot hybridization using supernatant from co-transfected cells. Recombinant vAc alpha hCG having a replacement of the viral polyhedrin gene, which is hyper-transcribed very late in the infection cycle, with the alpha hCG cDNA was purified after a single round of plaque purification. Insect cell culture infected with vAc alpha hCG, secreted high levels of hCG which was biologically active.


Development and characterization of a new plasmid delivery system based on chitosan-sodium deoxycholate nanoparticles.
Chitosan is one of the most promising polymers for drug delivery through the mucosal routes because of its polycationic, biocompatible, and biodegradable nature, and particularly due to its mucoadhesive and permeation-enhancing properties. Bile salts are known to interact with lipid membranes, increasing their permeability. The addition of bile salts to chitosan matrices may improve the delivery characteristics of the system, making it suitable for mucosal administration of bioactive substances. In the present study we have developed chitosan nanoparticles using sodium deoxycholate as a counter ion and evaluated their potential as gene delivery carriers. Chitosan-sodium deoxycholate nanoparticles (CS/DS) obtained via a mild ionic gelation procedure using different weight ratios were used to encapsulate plasmid DNA (pDNA) expressing a "humanized" secreted Gaussia Luciferase as reporter gene (pGLuc, 5.7 kDa). Mean particle size, polydispersity index and zeta potential were evaluated in order to select the best formulation for further in vitro studies. The nanoparticles presented an average size of 153-403 nm and a positive zeta potential ranging from +33.0 to +56.9 mV, for nanoparticles produced with CS/DS ratios from 1:4 to 1:0.6 (w:w), respectively. The pDNA was efficiently encapsulated and AFM studies showed that pDNA-loaded nanoparticles presented a more irregular surface due to the interaction between cationic chitosan and negatively charged pDNA which results in a more compact structure when compared to empty nanoparticles. Transfection efficiency of CS/DS-pDNA nanoparticles into moderately (AGS) and well differentiated (N87) gastric adenocarcinoma cell lines was determined by measuring the expression of luciferase, while cell viability was assessed using the MTT reduction. The CS/DS nanoparticles containing encapsulated pDNA were able to transfect both AGS and N87 cell lines, being more effective with AGS cells, the less differentiated cell line. The highest enzymatic activity was achieved with 20% pDNA encapsulated and after 24 h of transfection time. Low cytotoxicity was observed for the CS/DS nanoparticles either with or without pDNA, suggesting this could be a new potential vehicle for mucosal delivery of pDNA.


[Helicobacter pylori and the progression of gastric cancer: a 10-year cohort study].
To search the role of Helicobacter pylori (H. pylori) in the progression of gastric carcinogenesis. A cohort study was conducted by cluster randomized sampling in Linqu County, a rural area in Shandong Province in northeast China, where the mortality of gastric cancer (GC) is among the highest in the world. In 1989-1990, a gastroscopic examination and serum test was launched among subjects aged 35-64 from 14 randomized villages. Histological diagnosis of gastric mucosa and enzyme-linked immunosorbent assay was used to detect gastric lesions and anti-H. pylori of all participants. A repeated gastroscopic screening was offered to all cohort members in 1994 and 1999 respectively, and all the GC cases, regardless of natural ones or ones by gastroscopy, were registered in the follow-up periods. Fifty-eight cases of GC were identified in 2469 subjects during the 10-year follow-up, 44 were observed in 1603 H. pylori-positive persons (2.74%) and 14 in 866 H. pylori-negative persons (1.62%). The incidence rate of GC in H. pylori-positive is significantly higher than in H. pylori-negative (OR = 1.871, 95% CI: 1.012 - 3.459). There was no significant difference in the progression of gastric carcinogenesis between H. pylori-positive and H. pylori-negative (P > 0.05) among subjects with normal or superficial gastritis (SG) at baseline. In contrast, the significant difference was found in baseline chronic gastritis (CAG) group (P < 0.01), and the GC incidence rate in H. pylori-positive (7/615) is higher than in H. pylori-negative (0/470, P = 0.019). The difference of gastric lesions between H. pylori-positive and H. pylori-negative in subjects with intestinal metaplasia (IM) and dysplasia (DYS) at baseline was statistically significant after a 10-year follow-up (P < 0.05, P < 0.01, respectively), but the GC incidence rate in H. pylori-positive is similar to the rate in H. pylori-negative at the two groups (17/573 and 7/224 in IM group, P = 0.907; 19/368 and 7/122 in DYS group, P = 0.806). H. pylori is a key risk factor that prompts the transition from chronic atrophic gastritis to advanced precancerous lesions and influences the whole progression of precancerous gastric lesions. H. pylori, perhaps can not cause GC directly, increases the risk of GC in company with other carcinogens. H. pylori seemingly has no important effect on the development of GC when gastric mucosa is normal or superficial gastritis, but this conclusion is required to be further confirmed.


Ionic Liquid Promoted Diazenylation of N-Heterocyclic Compounds with Aryltriazenes under Mild Conditions.
An efficient, mild, and metal-free approach to direct diazenylation of N-heterocyclic compounds with aryltriazenes using Brønsted ionic liquid as a promoter has been developed for the first time. Many N-heterocyclic azo compounds were synthesized in good to excellent yields at room temperature under an open atmosphere. Notably, the promoter 1,3-bis(4-sulfobutyl)-1H-imidazol-3-ium hydrogen sulfate could be conveniently recycled and reused with the same efficacies for at least four cycles.


Testing the reliability and validity of computer-mediated social support measures among older adults: a pilot study.
With the increasing number of older adult online users, the Internet and e-mail are becoming a new source of social support for older adults. To assess this computer-mediated social support, two traditional social support measures were modified: (1) the Lubben Social Network Scale and (2) the Medical Outcomes Study Social Support Survey. The purpose of this pilot study was to test the reliability and validity of these modified measures. This study was a single group descriptive study with two data collection points. Data were collected using Web surveys. A total of 38 older adult participants completed the first survey; 35, the second survey. The findings of this preliminary study provided evidence for the reliability, content validity, and, to a limited extent, construct validity, of the modified measures. Additional studies with a larger representative sample are needed to further examine the psychometric aspects of these measures.


Symbolic interactionism and critical perspective: divergent or synergistic?
Throughout their history, symbolic interactionism and critical perspective have been viewed as divergent theoretical perspectives with different philosophical underpinnings. A review of their historical and philosophical origins reveals both points of divergence and areas of convergence. Their underlying philosophies of science and views of human freedom are different as is their level of focus with symbolic interactionism having a micro perspective and critical perspective using a macro perspective. This micro/macro difference is reflected in the divergence of their major concepts, goals and basic tenets. While their underlying philosophies are different, however, they are not necessarily contradictory and areas of convergence may include the concepts of reference groups and looking glass self within symbolic interactionism and ideological hegemony within critical perspective. By using a pragmatic approach and combining symbolic interactionism and critical perspectives, both micro and macro levels come into focus and strategies for change across individual and societal levels can be developed and applied. Application of both symbolic interactionism and critical perspective to nursing research and scholarship offers exciting new opportunities for theory development and research methodologies. In nursing education, these two perspectives can give students added insight into patients' and families' problems at the micro level while, at the same time, giving them a lens to see and tools to apply to problems at the macro level in health care. In nursing practice, a combined symbolic interactionism/critical perspective approach assists nurses to give high-quality care at the individual level while also working at the macro level to address the manufacturers of illness. New research questions emerge from this combination of perspectives with new possibilities for theory development, a transformation in nursing education, and the potential for new practice strategies that can address individual client and larger system problems through empowerment of clients and nurses.


Growth inhibitory effect of doxazosin on prostate and bladder cancer cells. Is the serotonin receptor pathway involved?
Doxazosin, an alpha1-adrenoceptor antagonist, is used for the treatment of benign prostatic hyperplasia (BPH) and hypertension. Alpha-adrenoceptor antagonists also inhibit growth and induce apoptosis in malignant prostatic cells. The apoptotic activity is independent of their capacity to antagonize alpha-adrenoceptors. The effect of doxazosin on the growth of prostate and bladder cancer cell lines was assessed and whether the growth inhibitory effect of doxazosin on prostate cancer cells is serotonin (5-hydroxtryptamine; 5HT)-dependent was investigated. PC3 (androgen-independent prostate cancer) and HT1376 (grade III transitional cell carcinoma) cells were plated. The cells were incubated with doxazosin. After 72 h, cell viability was assessed (crystal violet assay). Studies were also performed after incubating the PC3 cells with 5HT or 5HT(1B) agonists for a short duration, followed by the addition of doxazosin. Cell viability was assessed at 72 h. Doxazosin caused a dose-dependent inhibition of PC3 and HT1376 cell growth with a maximum inhibition of 80% (n=12, p < 0.0001) and 91% (n=12, p < 0.0001), respectively, at a concentration of 10(-4)M, at 72 h. Incubation of PC3 cells with 5HT or 5HT(1B) agonist, followed by addition of doxazosin, increased the percent of viable cells as compared to when the cells were treated with doxazosin alone. Doxazosin significantly inhibited prostate (PC3) and bladder cancer (HT1376) cell growth. Furthermore, prior incubation of PC3 cells with 5HT or 5HT(1B) agonist increased cell viability as compared to treatment with doxazosin alone. These findings may be related to the similarity between subtype 1 serotonin and adrenergic receptors. The effect of alpha1-adrenoceptor antagonists on tumour cell growth merits further investigation.


Serum from patients with Raynaud's phenomenon inhibits prostacyclin production.
Prostacyclin (PGI2) and PGE2, the predominant cyclooxygenase products of endothelial cells are potent vasodilators. An inability to produce appropriate concentrations of these prostanoids may be a factor in the pathogenesis of the digital vasospasm experienced by patients with Raynaud's phenomenon (RP). The effect of sera from normal subjects, patients with primary RP, and patients with RP in association with systemic sclerosis (SS) on the production of PGI2 and PGE2 by cultured human endothelial cells was investigated. All sera produced a dose-dependent inhibition of 6-keto-PGF1 alpha, but both the 10% and 20% sera from patients with RP and SS produced a significantly greater inhibition than control sera. The mean production of 6-keto-PGF1 alpha expressed in ng/10(4) cells was 2.278 (normal), 1.9311 (RP), and 2.1824 (SS) after incubation with 1% serum for 24 h. This decreased to 1.3647, 0.5927, and 0.4171, respectively following incubation with 20% sera for 24 h. This represented a 44% (normal), 76% (RP), and 83% (SS) inhibition of 6-keto-PGF1 alpha production compared with serum free media. Similar results were obtained after 1 h incubation experiments. There was a nonsignificant decrease in mean PGE2 production following similar incubations with 1% and 20% sera for 24 h. These results suggest that factor(s) present in the sera of patients with RP may reduce the ability of endothelial cells to synthesize or release the vasodilator and antiaggregatory prostanoid PGI2.


Mode shape reconstruction of an impulse excited structure using continuous scanning laser Doppler vibrometer and empirical mode decomposition.
For vibration testing, discrete types of scanning laser Doppler vibrometer (SLDV) have been developed and have proven to be very useful. For complex structures, however, SLDV takes considerable time to scan the surface of structures and require large amounts of data storage. To overcome these problems, a continuous scan was introduced as an alternative. In this continuous method, the Chebyshev demodulation (or polynomial) technique and the Hilbert transform approach have been used for mode shape reconstruction with harmonic excitation. As an alternative, in this paper, the Hilbert-Huang transform approach is applied to impact excitation cases in terms of a numerical approach, where the vibration of the tested structure is modeled using impulse response functions. In order to verify this technique, a clamped-clamped beam was chosen as the test rig in the numerical simulation and real experiment. This paper shows that with additional innovative steps of using ideal bandpass filters and nodal point determination in the postprocessing, the Hilbert-Huang transformation can be used to create a better mode shape reconstruction even in the impact excitation case.


Direct detection of the hydrolysis of nerve agent model compounds using a fluorescent probe.
Nerve agents are highly toxic organophosphorus compounds (OPs) that are used as chemical warfare agents. Developing a catalytic bioscavenger to efficiently detoxify nerve agents in the bloodstream of affected individuals has been recognized as an attractive approach to prevent nerve agent toxicity. However, the search for nerve agent catalysts has been hindered by the lack of efficient direct assays for nerve agent hydrolysis. In addition, authentic nerve agents are restricted and access to use for experiments by the general research community is prohibited. Herein we report development of a method that combines use of novel nerve agent model compounds possessing a thiocholine leaving group that reacts with the fluorescent thio-detection probe, BES-Thio, to afford detection of sub-micromolar amounts of nerve agent model compounds hydrolysis products. The detection sensitivity of BES-Thio assay was approximately 10 times better than the Ellman assay. This developed method is useful as a direct, sensitive screening method for evaluating OP hydrolysis efficiency from catalytic cholinesterases. When the assay was assembled in the presence of oxime, OP-inhibited cholinesterases that were able to be reactivated by specific oxime showed oxime-assisted enzyme-mediated OP hydrolysis. Therefore, this method is also useful to screen oxime analogs to identify novel agents that can reactivate OP-inhibited cholinesterases or to screen various enzymes to identify pseudo-catalytic bioscavengers that can be readily reactivated by clinically approved oximes.


Effects of short-term sugary beverage consumption on glucose control and cardiovascular disease risk factors: A randomized controlled parallel-arm trial.
To determine differences in glucose control and cardiovascular disease risk factors following three weeks of added soda, 100% fruit juice, or water in apparently healthy, college-aged adults. Thirty-six adults (18 males; 18 females) between the ages of 18 and 30 years of age. A 3-arm randomized controlled parallel-arm trial; at baseline and after three weeks consuming the assigned beverage, participants completed glucose control and cardiovascular disease risk factor assessments. There were no significant differences between beverage conditions for glucose control or cardiovascular disease risk factors (ps > 0.05). There were no significant changes in caloric intake or differences in caloric intake between conditions, p = 0.17. In healthy, young adults, under free-living conditions, short-term consumption of two commercially packaged servings of SBs did not lead to significant glucose control or cardiovascular disease risk factor changes, indicating potential compensation and/or resilience to negative short-term effects.


Epidemiology of nosocomial infection and resistant organisms in patients admitted for the first time to an acute rehabilitation unit.
The objectives of this study were to define the epidemiology of nosocomial bacterial colonization and infection and to define predictors of nosocomial infection among a cohort (n=423) of admissions to an acute rehabilitation unit. Overall, methicillin-resistant Staphylococcus aureus (MRSA) and enterococci were the most commonly identified colonizing organisms. Escherichia coli and Pseudomonas aeruginosa were the most commonly identified colonizing gram-negative bacilli. During 70 (16.5%) of the 423 hospitalizations in the unit, 94 nosocomial infections occurred. The most common infections were those of the urinary tract (30% of 94 infections) or a surgical site (17%), Clostridium difficile diarrhea (15%), and bloodstream infection (12.8%). Antibiotic-resistant bacteria most commonly caused bloodstream infection (41.7%) and surgical site infection (56.3%). Independent predictors of nosocomial infection at the time of admission were functional status (measured with the functional independence measure), APACHE III score, and spinal cord injury. In conclusion, gram-positive organisms were the predominant strains causing nosocomial colonization and infection. The logistic model, if verified, may be useful in defining patients who should be targeted for measures to prevent nosocomial infection.


Therapeutic efficacy of ABT-737, a Bcl-2 inhibitor, in a canine melanoma cell line.
The small molecule inhibitor, ABT-737, inhibits Bcl-2 that is overexpressed in many tumor cell lines and, in combination with an anticancer drug, can strongly enhance proapoptotic activity. In the present study, we evaluated the inhibitory activity of ABT-737 on the survival of a canine melanoma cell line (MCM-N1). MCM-N1 cell viability was decreased following 24- and 48-hr culture with ABT-737, depending on ABT-737 concentration, while cell viability was unchanged in controls. ABT-737 synergized with carboplatin to promote cell death. Notably, approximately 50% of MCM-N1 cells survived following culture with 2-4 µg/ml of carboplatin; whereas, less than 20% of MCM-N1 cells survived following culture with ABT-737 (1 mM) plus carboplatin (2-10 µg/ml).


Atypical Teratoid/Rhabdoid Tumor of the Sellar Region in an Adult With Long Survival: Case Report and Review of the Literature.
Atypical teratoid/rhabdoid tumor (AT/RT) is a highly malignant central nervous system neoplasm usually diagnosed in young children, although it can occur in adults. Prognosis for AT/RT is poor, with a median survival of 10 - 11 months. We report a rare case of adult sellar and suprasellar AT/RT in a 36-year-old female patient. She was treated with multi-modalities including surgery, chemotherapy and radiation. She markedly improved following treatment with no recurrence in 3 years follow-up. To our knowledge, this is the 11th case of an adult-onset AT/RT in the sellar or suprasellar region with favorable long-term outcome.


Prevalence and trends of the adult patient population in a pediatric emergency department.
Although pediatric emergency departments (PEDs) generally do not care for adult patients (≥21 years old), adult patients still present to PEDs with short-term complaints. The purpose of this study was to describe trends in the prevalence, the acuity, and the causes of adult patients presenting to a PED. Patients consisted of adults (≥21 years old) seen in a large, urban PED from January 1, 2004, to December 31, 2008. Data were obtained retrospectively from the electronic medical record. Data included demographics, triage acuity, primary codes according to the International Classification of Diseases, 9th Revision, insurance status, referred status, and disposition. There were 463,827 patient visits during the study period. Of these visits, 3361 (0.7%) were adult patients, with a mean (SD) age of 27.5 (9) years. During the 5-year study period, overall PED visits increased by 9% (from 85,987 to 93,753), whereas adult patient visits increased 29% (from 605 to 780). Of the adult patients seen, 1898 (55%) were white and 2100 (62%) were female. Moreover, 1465 (44%) were triaged either emergently or to the medical/trauma resuscitation room, 652 (20%) were admitted, and 677 (20%) were transferred to another facility. Of these adult patients, 712 (21%) were referred to our PED by a primary care provider or subspecialist, and 790 (29%) had no insurance. Adult visits to a large, urban PED have increased significantly during the past 5 years. Often, these patients have little or no insurance and present with a high acuity. Transitioning adult patients with long-term "pediatric" conditions and further training PED staff on how to care for adult patients are essential.


Mechanisms underlying the rules for associative plasticity at adult human neocortical synapses.
The neocortex in our brain stores long-term memories by changing the strength of connections between neurons. To date, the rules and mechanisms that govern activity-induced synaptic changes at human cortical synapses are poorly understood and have not been studied directly at a cellular level. Here, we made whole-cell recordings of human pyramidal neurons in slices of brain tissue resected during neurosurgery to investigate spike timing-dependent synaptic plasticity in the adult human neocortex. We find that human cortical synapses can undergo bidirectional modifications in strength throughout adulthood. Both long-term potentiation and long-term depression of synapses was dependent on postsynaptic NMDA receptors. Interestingly, we find that human cortical synapses can associate presynaptic and postsynaptic events in a wide temporal window, and that rules for synaptic plasticity in human neocortex are reversed compared with what is generally found in the rodent brain. We show this is caused by dendritic L-type voltage-gated Ca2+ channels that are prominently activated during action potential firing. Activation of these channels determines whether human synapses strengthen or weaken. These findings provide a synaptic basis for the timing rules observed in human sensory and motor plasticity in vivo, and offer insights into the physiological role of L-type voltage-gated Ca2+ channels in the human brain.


Rapid and Multiplexed Detection of Single Cells of Salmonella, Escherichia coli O157, and Shigella flexneri in Ground Beef by Flow Cytometry.
Salmonella, Escherichia coli O157, and Shigella flexneri are typical foodborne pathogens in ground beef, which can cause severe infection even when present as a single cell. Flow cytometry (FCM) methods are widely applied in the rapid detection of pathogens in food products. In this study, we report an FCM-based method for detecting single cells of Salmonella, E. coli O157, and S. flexneri in 25 g ground beef samples. We fluorescently labeled specific antibodies that could effectively identify bacterial cells, prepared single-cell samples by serial dilution, and optimized the pre-enrichment time. The results showed that 7 h of pre-enrichment is appropriate for sensitive single-cell detection by FCM. Finally, we evaluated this method in artificially contaminated and retail beef samples. This study outlines a novel highly sensitive FCM-based method to detect Salmonella, E. coli O157, and S. flexneri in beef samples within 8 h that can be applied to the rapid and multiplexed detection of foodborne pathogens.


An Improved Speciation Method Combining IC with ICPOES and Its Application to Iodide and Iodate Diffusion Behavior in Compacted Bentonite Clay.
An accurate and effective method combining ion chromatography (IC) and inductively coupled plasma optical emission spectrometry (ICP-OES) was applied in this work to qualitatively and quantitatively analyze individual and co-existing iodide (I-) and iodate (IO3-) at various concentrations. More specifically, a very strong linear relationship for the peak area for the co-existing I- and IO3- ions was reached, and a high resolution value between two peaks was observed, which proves the effectiveness of our combined IC-ICP-OES method at analyzing iodine species. We observed lower accessible porosity for the diffusion of both I- and IO3- in samples of bentonite clay using IC-ICP-OES detection methods, where the effective diffusion coefficient varied based on the anion exclusion effect and the size of the diffusing molecules. In fact, the distribution coefficients (Kd) of both I- and IO3- were close to 0, which indicates that there was no adsorption on bentonite clay. This finding can be explained by the fact that no change in speciation took place during the diffusion of I- and IO3- ions in bentonite clay. Our IC-ICP-OES method can be used to estimate the diffusion coefficients of various iodine species in natural environments.


Positron emission mammography-guided breast biopsy.
Positron emission mammography (PEM) is a technique to obtain planar images of the breast for detection of potentially cancerous, radiotracer-avid tumors. To increase the diagnostic accuracy of this method, use of minimally invasive methods (e.g., core biopsy) may be desirable for obtaining tissue samples from lesions detected with PEM. The purpose of this study was to test the capabilities of a novel method for performing PEM-guided stereotactic breast biopsies. The PEM system consisted of 2 square (10 x 10 cm) arrays of discrete scintillator crystals. The detectors were mounted on a stereotactic biopsy table. The stereotactic technique used 2 PEM images acquired at +/-15 degrees and a new trigonometric algorithm. The accuracy and precision of the guidance method was tested by placement of small point sources of (18)F at known locations within the field of view of the imager. The calculated positions of the sources were compared with the known locations. In addition, simulated stereotactic biopsies of a breast phantom consisting of a 10-mm-diameter gelatin sphere containing a concentration of (18)F-FDG consistent with that reported for breast cancer were performed. The simulated lesion was embedded in a 4-cm-thick slab of gelatin containing a commonly reported concentration of FDG, simulating a compressed breast (target-to-background ratio, approximately 8.5:1). An anthropomorphic torso phantom was used to simulate tracer uptake in the organs of a patient 1 h after a 370-MBq injection of FDG. Five trials of the biopsy procedure were performed to assess repeatability. Finally, a method for verifying needle positioning was tested. The positions of the point sources were successfully calculated to within 0.6 mm of their true positions with a mean error of +/-0.4 mm. The biopsy procedures, including the method for verification of needle position, were successful in all 5 trials in acquiring samples from the simulated lesions. The success of this new technique shows its potential for guiding the biopsy of breast lesions optimally detected with PEM.


[Psychiatric examination performed by phone to determine guardianship--is it legally valid?].
The administration of a psychiatric evaluation to determine guardianship entails the prerequisite of a full psychiatric examination of the patient. In psychogeriatrics, dementia is the common reason for measures to determine incompetence and guardianship and in general psychiatry it is applicable for the diagnosis of schizophrenia. Legal guardianship is determined by the court and can apply to aspects involving confidentiality such as the patient's assets or body or both, and its duration can be temporary or permanent. This is a case study of a 30 year old man who had never undergone a psychiatric examination. His parents reported behavior that was suggestive of a prolonged paranoid psychotic state for the past 8 years with deterioration in the last year. All attempts by his parents to bring him to a medical or psychiatric examination were refused by the patient. In order to prevent further deterioration of the situation, the family was advised to request legal guardianship for him. Due to his refusal to be examined and the lack of indication for a forced examination, a long taped phone conversation was conducted with the patient and later validated to ensure that this was the patient in question. This conversation together with heteroanamnesis, provided the basis for writing a psychiatric evaluation recommending the appointment of a legal guardian for the patient. To the best of our knowledge, the court's decision to appoint a legal guardian based on a telephone conversation is a precedent.