[Water-soluble modified derivatives of urokinase: fibrinolytic activity and other properties].
Urokinase modification by substances, possessing their own therapeutic activity, permits to obtain preparations of combined action on the enzyme basis, the catalytic properties of the modified enzyme being similar to those of the native one. The coupling of sodium nitroprusside to urokinase makes the action of the vasodilator more prolonged. Urokinase modification by heparin produces stabilized preparations, possessing fibrinolytic and anticoagulative activity. Derivatives of manifold modified urokinase have been experimentally obtained. Urokinase-heparin-sodium nitroprusside conjugates simultaneously exhibit fibrinolytic, hypertensive and anticoagulative effect. Urokinase coupling to fibrinogen via aliphatic diamine "spacer group" increases the affinity of the modified enzyme derivative to thrombus material. This provides the increased local fibrinolytic activity of the obtained urokinase preparation. The method suggested point out the new possible ways of creating highly effective therapeutics.


HER-2/neu detection in fine-needle aspirates of breast cancer: fluorescence in situ hybridization and immunocytochemical analysis.
We evaluated HER-2 receptor status by immunocytochemical and immunohistochemical analyses and fluorescence in situ hybridization (FISH) in 51 fine-needle aspiration (FNA) specimens together with the corresponding formalin-fixed, paraffin-embedded (FFPE) tissue samples obtained from surgically resected breast cancers. Three fixation methods were compared: ethanol, formalin, and CytoLyt-ThinPrep (Cytyc, Boxborough, MA). HER-2 was overexpressed and amplified in 8 (16%) of 51 FFPE specimens. Of the 8 cases, gene amplification was observed in 8 FNA specimens (100%) and overexpression in 2 (25%) ethanol-, 4 (50%) CytoLyt-, and 5 (63%) formalin-fixed FNA specimens. Strong pairwise kappa association between FISH results performed on FNA specimens and FFPE tissue samples (ethanol fixation, kappa = 0.848; ThinPrep, kappa = 0.918) and moderate (ThinPrep, kappa = 0.692; formalin fixation, kappa = 0.667) to poor (ethanol, kappa = 0.300) pairwise kappa agreement between tissue immunohistochemical and FNA immunocytochemical results was demonstrated. We conclude that HER-2 protein expression on cytologic preparations was insufficiently reliable for clinical use, whereas HER-2 gene amplification determined by FISH demonstrated strong and consistent correlation with HER-2 status of FFPE tissue samples.


Rational therapeutic choice for older patients with lymphoma.
The choice for an optimal treatment in older lymphoma patients is a real challenge for hemato-oncologists. They have to treat a potentially curative lymphoma, and concomitantly protect their patients from unacceptable toxicities. Some recommendations are provided for the major subtypes of lymphomas including the antitumoral treatment and primarily the optimal supportive care. All the recent literature data converge to say that the approach of an older patient with a malignant hemopathy is a multistep procedure. This process comprises the appraisal of life expectancy of the patient with or without the disease, the prognostic factors of the tumor, the functional, physiological and cognitive functions evaluation, the socio-economical environment and the patient's expectancy in terms of quality of life. Major progresses have been achieved in the management of diffuse large B cell lymphoma and mantle cell lymphoma in patients up to 80 and above 80 years old. With all these information in hands, the hematologist will decide if the treatment's objective is the standard treatment with optimal supportive care (fit patients), tailor-made adapted chemotherapy (unfit patients) or preservation of quality of life (frail patients).


Knowledge of breast cancer and breast self-examination practice among Iranian women in Hamedan, Iran.
In Iran, breast cancer is the most prevalent cancer in women and a major public health problem. A cross sectional study was carried out to determine knowledge on breast cancer and breast self- examination (BSE) practices of 384 females living in the city of Hamadan, Iran. A purposive sampling method was adopted and data were collected via face-to-face interviews based on a validated questionnaire developed for this study. Among respondents 268 (69.8%) were married and 144 (37.5%) of the respondents reported having a family history of breast cancer. One hundred respondents (26.0%) claimed they practiced BSE. Level of breast cancer knowledge was significantly associated with BSE practice (p=0.000). There was no association with demographic details (p<0.05). The findings showed that Iranian women's knowledge regarding breast cancer and the practice of BSE is inadequate. Targeted education should be implemented to improve early detection of breast cancer.


Expression of circZNF609 is Down-Regulated in Colorectal Cancer Tissue and Promotes Apoptosis in Colorectal Cancer Cells by Upregulating p53.
BACKGROUND Circular RNA (circRNA) is a special long-chain non-coding RNA produced during the process of intracellular RNA splicing. Also, circZNF609 is abundant in human tissues, with multiple functions in human diseases, but its role in colorectal cancer remains unknown. This study aimed to evaluate the expression of circZNF609 in tumor tissue and serum samples from patients with colorectal cancer and in colorectal cancer cell lines. MATERIAL AND METHODS The expression of circZNF609 was measured by quantitative polymerase chain reaction (q-PCR) in 45 paired tissue samples from patients with colorectal cancer and 46 serum samples from patients with colorectal cancer and healthy controls, and in the normal human colorectal cell line, FHC, and human colorectal cancer cell lines, HCT116 and HT29. Protein expression of proliferating cell nuclear antigen (PCNA), c-Myc, Bax, Bcl-2, and p53 was determined by Western blot. Cell apoptosis was measured by flow cytometry. RESULTS CircZNF609 was significantly down-regulated in colorectal cancer tissues compared with adjacent normal tissues and in the serum of patients with colorectal cancer compared with healthy controls, verified by receiver operating characteristic (ROC) curve analysis. There was low expression of circZNF609 in HCT116 cells, and overexpression inhibited cell proliferation but had no effect on PCNA and c-Myc protein expression. Expression of circZNF609 induced apoptosis and upregulated expression of the pro-apoptotic protein, Bax, down-regulated the expression of the anti-apoptotic protein, Bcl-2, and upregulated p53. CONCLUSIONS Expression of circZNF609 was down-regulated in colorectal cancer tissue and promoted apoptosis in colorectal cancer cells in vitro by upregulating p53.


[Bronchial adrenergic receptors and asthma. Tachyphylaxis and its prevention].
The majority of the clinical studies in healthy volunteers have shown that chronic inhalation or oral intake of sympathomimetics causes tachyphylaxis of the bronchial beta adrenergic receptors. We have observed in healthy subjects individual differences in the propensity to develop beta-adrenergic tachyphylaxis during a prolonged treatment with sympathomimetics. There was no relation between the development of beta-adrenergic tachyphylaxis and changes in bronchial responsiveness to methacholine. The problem is much more complex in the asthmatic patients. Several well controlled studies have however shown that chronic administration of sympathomimetics results in a significantly decreased sensitivity of the bronchial beta adrenergic receptor. This tachyphylaxis is mainly demonstrable as a shorter duration of action of the sympathomimetics. The clinical relevance of the beta adrenergic tachyphylaxis induced by prolonged treatment with sympathomimetics is probably minimal and has no relation with the relative resistance to sympathomimetics observed during acute severe asthma. Corticosteroids, given orally or parenterally, restore the sensitivity of the beta adrenergic receptors. In a double blind, placebo controlled study in healthy subjects we have observed that ketotifen prevents the development of a tachyphylaxis of the bronchial beta adrenergic receptor during prolonged treatment with inhaled sympathomimetics.


Tracking 'transitional' diadectomorphs in the earliest Permian of equatorial Pangea.
Diadectomorpha was a clade of large-bodied stem-amniotes or possibly early-diverging synapsids that established a successful dynasty of late Carboniferous to late Permian high-fiber herbivores. Aside from their fairly rich record of body fossils, diadectomorphs are also well-known from widely distributed tracks and trackways referred to as Ichniotherium. Here, we provide detailed description of a diadectomorph trackway and a manus-pes couple originating from two different horizons in the Asselian (lowermost Permian) of the Boskovice Basin in the Czech Republic. The specimens represent two distinct ichnotaxa of Ichniotherium, I. cottae and I. sphaerodactylum. Intriguingly, the I. cottae trackway described herein illustrates a 'transitional' stage in the posture evolution of diadectomorphs, showing track morphologies possibly attributable to a Diadectes-like taxon combined with distances between the successive manus and pes imprints similar to those observable in earlier-diverging diadectomorphs, such as Orobates. In addition, this trackway is composed of 14 tracks, including six well-preserved manus-pes couples, and thus represents the most complete record of Ichniotherium cottae described to date from the Asselian strata. In turn, the manus-pes couple, attributed here to I. sphaerodactylum, represents only the second record of this ichnotaxon from the European part of Pangea. Our study adds to the diversity of the ichnological record of Permian tetrapods in the Boskovice Basin which had been essentially unexplored until very recently.


Involvement of the mutated M protein in altered budding polarity of a pantropic mutant, F1-R, of Sendai virus.
Wild-type Sendai virus buds at the apical plasma membrane domain of polarized epithelial MDCK cells, whereas a pantropic mutant, F1-R, buds at both the apical and basolateral domains. In F1-R-infected cells, polarized protein transport and the microtubule network are impaired. It has been suggested that the mutated F and/or M proteins in F1-R are responsible for these changes (M. Tashiro, J. T. Seto, H.-D. Klenk, and R. Rott, J. Virol. 67:5902-5910, 1993). To clarify which gene or mutation(s) was responsible for the microtubule disruption which leads to altered budding of F1-R, MDCK cell lines containing the M gene of either the wild type or F1-R were established. When wild-type M protein was expressed at a level corresponding to that synthesized in virus-infected cells, cellular polarity and the integrity of the microtubules were affected to some extent. On the other hand, expression of the mutated F1-R M protein resulted in the formation of giant cells about 40 times larger than normal MDCK cells. Under these conditions, the effects on the microtubule network were enhanced. The microtubules were disrupted and polarized protein transport was impaired as indicated by the nonpolarized secretion of gp80, a host cell glycoprotein normally secreted from the apical domain, and bipolar budding of wild-type and F1-R Sendai viruses. The mutated F glycoprotein of F1-R was transported bipolarly in cells expressing the F1-R M protein, whereas it was transported predominantly to the apical domain when expressed alone or in cells coexpressing the wild-type M protein. These findings indicate that the M protein of F1-R is involved in the disruption of the microtubular network, leading to impairment of cellular polarity, bipolar transport of the F glycoprotein, and bipolar budding of the virus.


Behavioral and neural lateralization of vision in courtship singing of the zebra finch.
Along with human speech and language processing, birdsong has been one of the best-characterized model systems for understanding the relationship of lateralization of brain function to behavior. Lateralization of song production has been extensively characterized, and lateralization of song perception has begun to be studied. Here we have begun to examine whether behavior and brain function are lateralized in relation to communicative aspects of singing, as well. In order to monitor central brain function, we assayed the levels of several activity dependent immediate early genes after directed courtship singing. Consistent with a lateralization of visual processing during communication, there were higher levels of expression of both egr-1 and c-fos in the left optic tectum after directed singing. Because input from the eyes to the brain is almost completely contralateral in birds, these results suggest that visual input from the right eye should be favored during normal singing to females. Consistent with this, we further found that males sang more when they could use only their right eye compared to when they could use only their left eye. Normal levels of singing, though, required free use of both eyes to view the female. These results suggest that there is a preference for visual processing by the right eye and left brain hemisphere during courtship singing. This may reflect a proposed specialization of the avian left hemisphere in sustaining attention on stimuli toward which a motor response is planned.


Morphological features and length measurements of fetal lateral ventricles at 16-25 weeks of gestation by magnetic resonance imaging.
Normal growth of the lateral ventricles (LVs) was characterized three-dimensionally using magnetic resonance imaging (MRI) data from 16 human fetuses at 16-25 weeks of gestation. The LV was differentiated into four primary regions, the anterior horn, central parts, posterior horn, and inferior horn, at 16 weeks of gestation. The LV changed shape mainly by elongation and narrowing, which corresponded to the external and internal growth of the surrounding cerebrum. Six length parameters measured in the LV correlated with biparietal diameter by simple regression analysis (R(2) range, 0.56-0.93), which may be valuable for establishing a standardized prenatal protocol to assess fetal well-being and development across intrauterine periods. No correlation was found between biparietal diameter and LV volume (R(2) = 0.13).


Potential of the essential oil from Pimenta pseudocaryophyllus as an antimicrobial agent.
This study evaluated the effectiveness of the essential oil of Pimenta pseudocaryophyllus in inhibiting the growth of the main bacteria responsible for bad perspiration odor (Staphylococcus epidermidis, Proteus hauseri, Micrococcus yunnanensis and Corynebacterium xerosis). The chemical profile of the essential oil was evaluated by high-resolution gas chromatography (HR-GC) and four constituents were identified, eugenol being the major component (88.6%). The antimicrobial activity was evaluated by means of the turbidimetric method, using the microdilution assay. The minimum inhibitory concentration (MIC) values of the essential oil ranged from 500 to 1,000 μg mL⁻¹. Scanning electron microscope (SEM) observations confirmed the physical damage and morphological alteration of the test bacteria treated with the essential oil, reference drugs and eugenol. The findings of the study demonstrated that this essential oil can be used in the formulation of personal care products.


Adverse Effect of T-2 Toxin and the Protective Role of Selenium and Vitamin E on Peripheral Blood B lymphocytes.
T-2 mycotoxin belongs to the Trichothecene family and has damaging effects on the immune system. To investigate the toxic effect of T-2 toxin on the percentage of peripheral blood B lymphocytes and the potential protective role of selenium and vitamin E. Frequencies of B lymphocytes (CD19+) were analyzed after injection of sublethal doses of T-2 toxin into Balb/c mice at different time points, using flowcytometry. Additionally, the effects of selenium and vitamin E on B lymphocyte, as either prophylaxis or simultaneously administered with T-2 toxin, were investigated. After injection of a sublethal dose of T-2 toxin, the number of B cells (CD19+) significantly decreased at 12 h and became normal at 72 h. When selenium was injected both 24 h before and simultaneously with T-2 toxin, it was able to inhibit B lymphocyte (CD19+) reduction. In contrast, injecting vitamin E, 24 h before or simultaneously with T-2 toxin did not regulate B lymphocyte alteration. Selenium plays pivotal role on altered B lymphocyte subset induced by T-2 toxin comparing to vitamin E.


Co-trimoxazole versus azithromycin for the treatment of undifferentiated febrile illness in Nepal: study protocol for a randomized controlled trial.
Undifferentiated febrile illness (UFI) includes typhoid and typhus fevers and generally designates fever without any localizing signs. UFI is a great therapeutic challenge in countries like Nepal because of the lack of available point-of-care, rapid diagnostic tests. Often patients are empirically treated as presumed enteric fever. Due to the development of high-level resistance to traditionally used fluoroquinolones against enteric fever, azithromycin is now commonly used to treat enteric fever/UFI. The re-emergence of susceptibility of Salmonella typhi to co-trimoxazole makes it a promising oral treatment for UFIs in general. We present a protocol of a randomized controlled trial of azithromycin versus co-trimoxazole for the treatment of UFI. This is a parallel-group, double-blind, 1:1, randomized controlled trial of co-trimoxazole versus azithromycin for the treatment of UFI in Nepal. Participants will be patients aged 2 to 65 years, presenting with fever without clear focus for at least 4 days, complying with other study criteria and willing to provide written informed consent. Patients will be randomized either to azithromycin 20 mg/kg/day (maximum 1000 mg/day) in a single daily dose and an identical placebo or co-trimoxazole 60 mg/kg/day (maximum 3000 mg/day) in two divided doses for 7 days. Patients will be followed up with twice-daily telephone calls for 7 days or for at least 48 h after they become afebrile, whichever is later; by home visits on days 2 and 4 of treatment; and by hospital visits on days 7, 14, 28 and 63. The endpoints will be fever clearance time, treatment failure, time to treatment failure, and adverse events. The estimated sample size is 330. The primary analysis population will be all the randomized population and subanalysis will be repeated on patients with blood culture-confirmed enteric fever and culture-negative patients. Both azithromycin and co-trimoxazole are available in Nepal and are extensively used in the treatment of UFI. Therefore, it is important to know the better orally administered antimicrobial to treat enteric fever and other UFIs especially against the background of fluoroquinolone-resistant enteric fever. ClinicalTrials.gov, ID: NCT02773407 . Registered on 5 May 2016.


High cervical arteriovenous fistulas fed by dural and spinal arteries and draining into a single medullary vein: report of 3 cases.
The authors previously reported a case of complex arteriovenous fistula (AVF) at C-1 with multiple dural and spinal feeders that were linked with a common medullary venous channel. The purpose of the present study was to collect similar cases and analyze their angioarchitecture to gain a better understanding of this malformation. Three such cases, affecting 2 males and 1 female in their 60s who had presented with hematomyelia (2) or progressive myelopathy (1), were treated surgically, and the operative findings from all 3 cases were compared using digital subtraction angiography (DSA) to determine the angioarchitecture. The C-1 and C-2 radicular arteries and anterior and posterior spinal arteries supplied feeders to a single medullary draining vein in various combinations and via various routes. The drainage veins ran along the affected ventral nerve roots and lay ventral to the spinal cord. The sites of shunting to the vein were multiple: dural, along the ventral nerve root in the subarachnoid space, and on the spinal cord, showing a vascular structure typical of dural AVF, that is, a direct arteriovenous shunt near the spinal root sleeve fed by one or more dural arteries and ending in a single draining vein, except for intradural shunts fed by feeders from the spinal arteries. In 2 cases with hemorrhagic onset the drainer flowed rostrally, and in 1 case associated with congestive myelopathy the drainer flowed both rostrally and caudally. Preoperative determination of the shunt sites and feeding arteries was difficult because of complex recruitment of the feeders and multiple shunt sites. The angioarchitecture in these cases was clarified postoperatively by meticulous comparison of the DSA images and operative video. Direct surgical intervention led to a favorable outcome in all 3 cases. A high cervical complex AVF has unique angioarchitectural characteristics different from those seen in the other spinal regions.


[Nursing intervention in surgery to prevent pulmonary complications].
The authors describe the predisposing factors of post-operative pulmonary complications (old age, malbalanced hydratation and nutrition, exacerbation of chronic obstructive pulmonary diseases) as well as the aggravating factors (anesthesia, immobilization in bed, abdominal distention, pain). They present the objectives of nursing intervention, pre and post operative measures to prevent pulmonary complications, early identification of clinical signs of respiratory failure, and treatment.


Association of dietary intake of fat and fatty acids with risk of breast cancer.
High intakes of fat and specific fatty acids, including total, animal, saturated, polyunsaturated, and trans-unsaturated fats, have been postulated to increase breast cancer risk. To determine whether intakes of fat and fatty acids are associated with breast cancer. Cohort study (Nurses' Health Study) conducted in the United States beginning in 1976. A total of 88795 women free of cancer in 1980 and followed up for 14 years. Relative risk (RR) of invasive breast cancer for an incremental increase of fat intake, ascertained by food frequency questionnaire in 1980, 1984, 1986, and 1990. A total of 2956 women were diagnosed as having breast cancer. Compared with women obtaining 30.1% to 35% of energy from fat, women consuming 20% or less had a multivariate RR of breast cancer of 1.15 (95% confidence interval [CI], 0.73-1.80). In multivariate models, the RR (95% CI) for a 5%-of-energy increase was 0.97 (0.94-1.00) for total fat, 0.98 (0.96-1.01) for animal fat, 0.97 (0.93-1.02) for vegetable fat, 0.94 (0.88-1.01) for saturated fat, 0.91 (0.79-1.04) for polyunsaturated fat, and 0.94 (0.88-1.00) for monounsaturated fat. For a 1% increase in energy from trans-unsaturated fat, the values were 0.92 (0.86-0.98), and for a 0.1% increase in energy from omega-3 fat from fish, the values were 1.09 (1.03-1.16). In a model including fat, protein, and energy, the RR for a 5% increase in total fat, which can be interpreted as the risk of substituting this amount of fat for an equal amount of energy from carbohydrate, was 0.96 (95% CI, 0.93-0.99). In similar models, no significant association of risk was evident with any major types of fat. We found no evidence that lower intake of total fat or specific major types of fat was associated with a decreased risk of breast cancer.


A call for refining the role of humic-like substances in the oceanic iron cycle.
Primary production by phytoplankton represents a major pathway whereby atmospheric CO2 is sequestered in the ocean, but this requires iron, which is in scarce supply. As over 99% of iron is complexed to organic ligands, which increase iron solubility and microbial availability, understanding the processes governing ligand dynamics is of fundamental importance. Ligands within humic-like substances have long been considered important for iron complexation, but their role has never been explained in an oceanographically consistent manner. Here we show iron co-varying with electroactive humic substances at multiple open ocean sites, with the ratio of iron to humics increasing with depth. Our results agree with humic ligands composing a large fraction of the iron-binding ligand pool throughout the water column. We demonstrate how maximum dissolved iron concentrations could be limited by the concentration and binding capacity of humic ligands, and provide a summary of the key processes that could influence these parameters. If this relationship is globally representative, humics could impose a concentration threshold that buffers the deep ocean iron inventory. This study highlights the dearth of humic data, and the immediate need to measure electroactive humics, dissolved iron and iron-binding ligands simultaneously from surface to depth, across different ocean basins.


Drugs dispensed in primary care during pregnancy: a record-linkage analysis in Tayside, Scotland.
For many regularly used drugs, evidence for safe use in pregnancy has not been established. Despite this, international studies have identified high levels of drug prescribing among pregnant women. To investigate the patterns of prescribing of drugs to women who gave birth in Tayside, Scotland, in 2007. Scottish maternity records were linked to dispensed prescribing data for all women who gave birth in Tayside in 2007. Drugs prescribed were coded according to the US FDA classification for risks of drugs in pregnancy. Patterns of prescribing were investigated during the 3 trimesters of pregnancy and the 3 months prior to conception. Prescribing in pregnancy was common, with 21 093 prescriptions dispensed to 3356 (85.2%) of the 3937 women. The most frequently prescribed drugs were antacids, antibacterials, oral iron, folic acid preparations and analgesics. Category A drugs (positive evidence of safety in pregnancy) and Category B drugs (some evidence of safety in pregnancy) accounted for 19.6% and 26.9% of all prescriptions dispensed, respectively. Prescribing of Category X drugs (evidence of risk to the fetus; use contraindicated in women who are or may become pregnant) during pregnancy was rare, with 112 prescriptions dispensed to 68 women (1.7%). Most of these were oral contraceptives or sex hormones. Prescribing of Category X drugs fell markedly during the first trimester and remained very low thereafter. Category D drugs (evidence of risk to the fetus but benefits of therapy may outweigh the potential risk) [432] were dispensed to 166 women (4.2%) during pregnancy. The most commonly prescribed Category D drugs were anxiolytics, nicotine replacement therapy and antiepileptic drugs. The frequency of prescribing of Category D drugs reduced in the third trimester. Prescribing of Category C drugs (insufficient evidence to know whether they are harmful) was common. Thirty percent of women received a total of 3641 Category C prescriptions, which accounted for 17.3% of all prescriptions issued during pregnancy. Prescribing of Category C drugs showed only a very modest decline during pregnancy. No FDA code was available for 4035 prescriptions issued (87 different items), the majority of which were for antacids and preparations for indigestion. More than 40% of women received such medications. Prescribing of drugs during pregnancy was very common, but the levels of prescribing of drugs that are known to be harmful were low. Much of the prescribing was for drugs related to the pregnancy. While this study provides some evidence that primary-care prescribers in Tayside are prescribing potentially harmful drugs appropriately and with caution during pregnancy, safety data during pregnancy are unavailable for many drugs that are commonly prescribed.


Meta-analysis of plasma homocysteine, serum folate, serum vitamin B(12), and thermolabile MTHFR genotype as risk factors for retinal vascular occlusive disease.
To assess the role of plasma total homocysteine (tHcy) levels, serum folate and vitamin B(12)levels, and homozygosity for the thermolabile methylenetetrahydrofolate reductase genotype (TT) as risk factors for retinal vascular occlusive disease. Meta-analysis of literature. A MEDLINE search was performed to identify all published case-control studies of plasma tHcy levels, serum folate and vitamin B(12) levels, and TT genotype in persons with retinal vascular occlusive disease. Main outcome measures included calculation of plasma tHcy, serum folate, and serum vitamin B(12) standard differences and odds ratios (OR) of TT genotype between cases and controls. In total, 614 patients with all types of retinal vein occlusion had higher plasma tHcy levels than 762 control subjects (standard difference, 0.867; 95% confidence interval [CI] = 0.735, 0.999; P <.001). Plasma tHcy levels were also higher in 154 patients with retinal artery occlusion compared with 358 control subjects (standard difference 1.174; 95% CI = 0.947, 1.402; P <.001). Serum folates, but not vitamin B(12) levels, were lower in 287 patients with retinal vascular occlusion than in the same number of control subjects (standard difference, 0.508; 95% CI = 0.340, 0.675; P <.001; and -0.060; 95% CI = -0.024, 0.104; P =.474, respectively). Similar proportions of 690 patients with retinal vein occlusion and 2754 control subjects demonstrated the TT genotype (OR = 1.332; 95% CI = 0.995, 1.783; P =.054) as did 152 patients with retinal artery occlusions and 435 control subjects (OR = 1.716; 95% CI = 0.977, 3.014; P =.060). Retinal vascular occlusion is associated with elevated plasma tHcy levels and low serum folate levels, but not serum vitamin B(12) levels and TT genotype. Until a prospective multicenter trial is undertaken, plasma tHcy levels and serum folate levels should be determined in patients with retinal vascular occlusions, and dietary supplementation with low doses of folate and vitamin B(12) should be considered for affected persons.


Dopamine D5 receptor modulates male and female sexual behavior in mice.
Dopamine exerts its actions through at least five receptor (DAR) isoforms. In female rats, D5 DAR may be involved in expression of sexual behavior. We used a D5 knockout (D5KO) mouse to assess the role of D5 DAR in mouse sexual behavior. Both sexes of D5KO mice are fertile and exhibit only minor disruptions in exploratory locomotion, startle, and prepulse inhibition responses. This study was conducted to characterize the sexual behavior of male and female D5KO mice relative to their WT littermates. Female WT and D5KO littermates were ovariectomized and given a series of sexual behavior tests after treatment with estradiol benzoate (EB) and progesterone (P). Once sexual performance was optimal the dopamine agonist, apomorphine (APO), was substituted for P. Male mice were observed in pair- and trio- sexual behavior tests. To assess whether the D5 DAR is involved in rewarding aspects of sexual behavior, WT and D5KO male mice were tested for conditioned place preference. Both WT and D5KO females can display receptivity after treatment with EB and P, but APO was only able to facilitate receptivity in EB-primed WT, not in D5KO, mice. Male D5KO mice display normal masculine sexual behavior in mating tests. In conditioned preference tests, WT males formed a conditioned preference for context associated with either intromissions alone or ejaculation as the unconditioned stimulus. In contrast, D5KO males only showed a place preference when ejaculation was paired with the context. In females, the D5 DAR is essential for the actions of dopamine on receptivity. In males, D5 DAR influences rewarding aspects of intromissions. Taken together, the work suggests that the D5 receptor mediates dopamine's action on sexual behavior in both sexes, perhaps via a reward pathway.


Design and Manufacture of Data Gloves for Rehabilitation Training and Gesture Recognition Based on Flexible Sensors.
This work takes the production and usage scenarios of the data glove as the research object and studies the method of applying the flexible sensor to the data glove. Many studies are also devoted to exploring the transplantation of flexible sensors to data gloves. However, this type of research still lacks the display of specific application scenarios such as gesture recognition or hand rehabilitation training. A small amount of experimental data and theoretical analysis are difficult to promote the development of flexible sensors and flexible data gloves design schemes. Therefore, this study uses the self-made flexible sensor of the research group as the core sensing unit to produce a flexible data glove to monitor the bending changes of the knuckles and then use it for simple gesture recognition and rehabilitation training.


Association between individual wheelchair skills and fitness in community-dwelling manual wheelchair users with spinal cord injuries.
Wheelchair skills are a key component to promotion of community participation among persons with spinal cord injury (SCI). The objective of this secondary analysis was to examine the association between individual wheelchair skills from the Wheelchair Skills Test Questionnaire (WST-Q) and fitness among community-dwelling adults with SCI. Twenty-six adults were recruited to complete the WST-Q and a standard graded aerobic wheelchair exercise test on a motorized treadmill for assessing peak power output (POpeak). Spearman Rho rank-order correlation (ρ) analyses indicated statistically significant correlations between POpeak and six basic (ρ = 0.41-0.57), eight intermediate (ρ = 0.44-0.59), and nine advanced (ρ = 0.42-0.80) WST-Q skill scores. After controlling for sex and injury level (Partial Spearman Rho rank order) significant correlations persisted for four advanced skills (i.e., descends high curb, turns in place in wheelie position, descends steep incline in wheelie position, descends high curb in wheelie position; ρ = 0.46-0.59) and one additional skill (i.e., ascends high curb ρ = 0.51). More advanced wheelchair skills are significantly associated with fitness in persons with SCI. The directionality of the skills-fitness relationship, specifically whether wheelchair skills facilitate greater fitness or fitness is a prerequisite for certain wheelchair skills needs to be determined in future, larger studies. However, results from this study provide a comprehensive list of wheelchair skills that are associated with fitness that can be directly applied to guide further research and practice promoting community participation among persons with SCI.Implications for RehabilitationSignificant positive associations exist between advanced wheelchair skills (i.e., descends high curb, turns in place in wheelie position, descends steep incline in wheelie position, descends high curb in wheelie position and ascends high curb) and fitness in manual wheelchair users with spinal cord injury (SCI).This study provides a list of skills associated with fitness to guide clinical practice and areas for further rehabilitation research assessing the directionality of the relationship between fitness and wheelchair skills.


The effect of electroacupuncture on proteomic changes in the motor cortex of 6-OHDA Parkinsonian rats.
Electroacupuncture (EA) has been reported to alleviate motor deficits in Parkinson's disease (PD) patients, and PD animal models. However, the mechanisms by which EA improves motor function have not been investigated. We have employed a 6-hydroxydopamine (6-OHDA) unilateral injection induced PD model to investigate whether EA alters protein expression in the motor cortex. We found that 4weeks of EA treatment significantly improved spontaneous floor plane locomotion and rotarod performance. High-throughput proteomic analysis in the motor cortex was employed. The expression of 54 proteins were altered in the unlesioned motor cortex, and 102 protein expressions were altered in the lesioned motor cortex of 6-OHDA rats compared to sham rats. Compared to non-treatment PD control, EA treatment reversed 6 proteins in unlesioned and 19 proteins in lesioned motor cortex. The present study demonstrated that PD induces proteomic changes in the motor cortex, some of which are rescued by EA treatment. These targeted proteins were mainly involved in increasing autophagy, mRNA processing and ATP binding and maintaining the balance of neurotransmitters.


Effect of pulmonary rehabilitation on functional exercise capacity and hypoxemia in patients with interstitial lung diseases: a retrospective study.
Introduction: Interstitial lung diseases (ILDs) are a heterogeneous group of lung disorders characterized by dyspnea on exertion, exercise-induced hypoxemia and reduced exercise tolerance. There are some evidences that pulmonary rehabilitation (PR) successfully treats these manifestations. Objective: To identify if pulmonary rehabilitation can achieve a clinically significant improvement of functional exercise capacity measured by 6-minute walk test (6-MWT) and arterial blood gases analysis (ABG) in patients with ILDs. Methods: A retrospective secondary analysis of the patients' records from in-patients of a pulmonary rehabilitation center between 2012 and 2015. Profiles of 38 patients who had completed 4-6 PR weeks were included. 6-MWT distance, dyspnea and fatigue Borg score and ABG at baseline and the end of the pulmonary rehabilitation were compared. Results: There was a statistically and clinically significant improvement in 6-MWT distance after PR with a mean difference for change in distance walked of 68.5±54.2 m. The pre post PR variation of dyspnea and fatigue Borg score significantly improved (-2.3±3.7, and -1.7±2.9, always p≤0.001). Among the ABG parameters, only the resting PaO2 showed a significant improvement after PR (Delta PaO2= 4.6±8.5 mmHg, p=0.005). Conclusions: A 4-6 week of PR improves functional exercise capacity and hypoxemia in patients with ILDs. (Sarcoidosis Vasc Diffuse Lung Dis 2018; 35: 245-251).


Significance of KRAS, NRAS, BRAF and PIK3CA mutations in metastatic colorectal cancer patients receiving Bevacizumab: a single institution experience.
Background. KRAS mutation is an important predictive and prognostic factor for patients receiving anti-EGFR therapy. An expanded KRAS, NRAS, BRAF, PIK3CA mutation analysis provides additional prognostic information, but its role in predicting bevacizumab efficacy is unclear. The aim of our study was to evaluate the incidence of KRAS, NRAS, BRAF and PIK3CA mutations in metastatic colorectal cancer patients receiving first line oxaliplatin based chemotherapy with or without bevacizumab and to evaluate their prognostic and predictive significance. Methods. 55 patients with the first-time diagnosed CRC receiving FOLFOX ± bevacizumab were involved in the study. Tumour blocks were tested for KRAS mutations in exons 2, 3 and 4, NRAS mutations in exons 2, 3 and 4, BRAF mutation in exon 15 and PIK3CA mutations in exons 9 and 20. The association between mutations and clinico-pathological factors, treatment outcomes and survival was analyzed. Results. KRAS mutations were detected in 67.3% of the patients, BRAF in 1.8%, PIK3CA in 5.5% and there were no NRAS mutations. A significant association between the high CA 19-9 level and KRAS mutation was detected (mean CA 19-9 levels were 276 and 87 kIU/l, respectively, p = 0.019). There was a significantly higher response rate in the KRAS, NRAS, BRAF and PIK3CA wild type cohort receiving bevacizumab compared to any gene mutant type (100 and 60%, respectively, p = 0.030). The univariate Cox regression analysis did not confirm KRAS and other tested mutations as prognostic factors for PFS or OS. Conclusions. Our study revealed higher KRAS and lower NRAS, BRAF and PIK3CA mutation rates in the Lithuanian population than those reported in the literature. KRAS mutation was associated with the high CA 19-9 level and mucinous histology type, but did not show any predictive or prognostic significance. The expanded KRAS, NRAS, BRAF and PIK3CA mutation analysis provided additional significant predictive information.


New Approach for Differentiation of Bone Marrow Mesenchymal Stem Cells Toward Chondrocyte Cells With Overexpression of MicroRNA-140.
Mesenchymal stem cells are widely stimulated by transforming growth factor beta-3 (TGFβ3) for chondrocyte differentiation. The objective of our study was to establish a new method for differentiation of human mesenchymal stem cells toward chondrocyte by overexpression of MicroRNA-140 (miR-140), and also this method was compared with method of induction with TGFβ3 in high-cell density culture systems. Mesenchymal stem cells were harvested from bone marrow of human. We prepared vectors and then was used for recombinant Lenti virus production in HEK-293 cell. Transducted cells were cultured in monolayer culture system and were harvested after days 7, 14, and 21. Real time polymerase chain reaction (RT-PCR) was performed to evaluate the cartilage-specific genes in the mRNA levels. Also, in order to confirm our results, we have done immunocytochemistry technique. Bone marrow mesenchymal stem cells (BMSCs) were transducted with recombinant Lenti virus, and miR-140 was expressed. Immunocytochemical method confirmed the differentiation of BMSC toward chondrocyte with handling cartilage matrix genes. Also real-time PCR showed that after expression of miR-140 in transducted BMSCs significantly increased gene expression of collagen type II and aggrecan and downregulated expression of collagen type I when compared with the mRNA levels measured in nontransducted BMSCs. These results were compatible compared with TGFβ3 induction method as control positive. In this study, we described a new approach and technique that may be applied for differentiation of BMSCs to chondrocyte instead of stimulation with TGFβ3. Our data implies that miR-140 is a potent chondrogenic differentiation inducer for BMSCs, and we have shown increasing chondrogenic differentiation by using miR-140 overexpression.


Balancing Legitimate Critical-Care Interests: Setting Defensible Care Limits Through Policy Development.
Critical-care decision making is highly complex, given the need for health care providers and organizations to consider, and constructively respond to, the diverse interests and perspectives of a variety of legitimate stakeholders. Insights derived from an identified set of ethics-related considerations have the potential to meaningfully inform inclusive and deliberative policy development that aims to optimally balance the competing obligations that arise in this challenging, clinical decision-making domain. A potential, constructive outcome of such policy engagement is the collaborative development of an as-fair-as-possible dispute resolution process that incorporates an appropriated-justified, defensible critical-care obligation threshold.


Use of Individualized Learning Plans to Facilitate Feedback Among Medical Students.
Self-regulated learning theory suggests that individualized learning plans can benefit medical trainees by providing a structured means of goal setting, self-monitoring, and self-evaluation. External feedback also plays an important role in affecting learner motivations, perceptions, and self-evaluations. Accordingly, having learners share individualized learning plans with preceptors might promote self-regulated learning by helping align the feedback they receive with their learning goals. Hypothesis: We hypothesized having medical students share individualized learning plans with attendings and residents would improve the quality of the feedback they received, increase the likelihood that feedback correlated to their learning goals, and improve their perceptions of feedback received. Method: In this multisite study, third-year medical students on their pediatric clerkship created individualized learning plans and shared them with residents and attendings by writing a learning goal on at least one of their required faculty feedback forms. The quality of feedback on forms with versus without a learning goal written on top was scored using a validated scoring tool and compared using a Wilcoxon signed-ranks test, and the frequency with which feedback directly correlated to a student learning goal on forms with versus without a learning goal written on top was compared using a chi-square test. Students completed a post-clerkship survey rating the quality of feedback and teaching they received, perceptions of the individualized learning plans, progress toward achieving learning goals, and whether or not they received teaching and/or feedback related to learning goals. Results: Thirty-six students completed a total of 108 learning goals and 181 feedback forms, of which 42 forms (23.2%) had a learning goal written on top. The mean (SD) feedback score between forms with [3.9 (0.9)] versus without [3.6 (0.6)] a learning goal written on top was not different (p = .113). Feedback on forms with a learning goal written on top was more likely to correlate to a student learning goal than feedback on forms without a learning goal (92.9% vs 23.0% respectively, p < .001). Student perceptions of the usefulness of learning goals did not differ between students who reported receiving teaching or feedback related to a learning goal and those who did not. Conclusions: Sharing individualized learning plans with preceptors helped align feedback with learning goals but did not affect the quality of feedback. Further research should examine the bidirectional relationship between individualized learning plans and feedback in light of other contextual and interpersonal factors.


Whole-brain morphometry in Canadian soldiers with posttraumatic stress disorder.
Patients with posttraumatic stress disorder (PTSD) display several structural brain differences when compared with healthy individuals. However, findings are particularly inconsistent for soldiers with PTSD. Here, we characterized the brain morphometry of 37 soldiers from the Canadian Armed Forces with adulthood war-related PTSD using structural magnetic resonance imaging. We assessed time since trauma, as well as PTSD, depressive, and anxiety symptoms with the Modified PTSD Symptoms Scale, Beck Depression Inventory, and Beck Anxiety Inventory, respectively. Whole-brain morphometry was extracted with FreeSurfer and compared with a validated normative database of more than 2700 healthy individuals. Volume and thickness from several regions differed from the norms. Frontal regions were smaller and thinner, particularly the superior and rostral middle frontal gyri. Furthermore, smaller left rostral middle frontal gyrus, left pericalcarine cortex, and right fusiform gyrus were associated with more recent trauma. All subcortical structures were bigger, except the hippocampus. These findings suggest a particular brain morphometric signature of PTSD in soldiers. Smaller and thinner frontal and larger subcortical regions support impaired top-down and/or downregulation of emotional response in PTSD. Finally, the correlation of smaller frontal, temporal, and occipital regions with more recent trauma might inform future therapeutic approaches.


Hybridization following population collapse in a critically endangered antelope.
Population declines may promote interspecific hybridization due to the shortage of conspecific mates (Hubb's 'desperation' hypothesis), thus greatly increasing the risk of species extinction. Yet, confirming this process in the wild has proved elusive. Here we combine camera-trapping and molecular surveys over seven years to document demographic processes associated with introgressive hybridization between the critically endangered giant sable antelope (Hippotragus niger variani), and the naturally sympatric roan antelope (H. equinus). Hybrids with intermediate phenotypes, including backcrosses with roan, were confirmed in one of the two remnant giant sable populations. Hybridization followed population depletion of both species due to severe wartime poaching. In the absence of mature sable males, a mixed herd of sable females and hybrids formed and grew progressively over time. To prevent further hybridization and recover this small population, all sable females were confined to a large enclosure, to which sables from the other remnant population were translocated. Given the large scale declines in many animal populations, hybridization and introgression associated with the scarcity of conspecific mates may be an increasing cause of biodiversity conservation concern. In these circumstances, the early detection of hybrids should be a priority in the conservation management of small populations.


Development of a vibrotactile cueing device that implicitly increases walking speed during gait training in stroke patients: an observational case series study.
One of the main sequelae of stroke is difficulty walking, which is characterised by decreased walking speed and asymmetrical walking patterns. Physical therapists often rely on explicit motor learning strategies, i.e., providing mainly verbal instructions for how movements should be performed. However, the voluntary movement induced by explicit instruction may lead to associated unintended muscle contractions or higher cognitive demand, which could be detrimental. We introduce a vibrotactile cueing device that implicitly improves walking speed. The stroke patient walks while alternating vibrational cues are given to the left and right sides of their waist. At each specified step, cueing frequency increases in the cueing group without the patient's awareness. The four patients in the cueing group did not notice the increase in walking speed during training; however, we observed an improvement in walking speed and cadence in patients using the proposed cueing system, which was maintained during the posttest phase. Additionally, patients using the cueing system were able to suppress excessive compensatory movements during training compared with patients who did not use the system. This case series study indicates that the proposed system for gait rehabilitation of stroke patients can enable an increase in walking speed without excessive effort.


Increased probiotic yogurt or resistant starch intake does not affect isoflavone bioavailability in subjects consuming a high soy diet.
Probiotics and prebiotics that affect gut microflora balance and its associated enzyme activity may contribute to interindividual variation in isoflavone absorption after soy intake, possibly enhancing isoflavone bioavailability. This study examined the effects of the consumption of bioactive yogurt (a probiotic) or resistant starch (a known prebiotic) in combination with high soy intake on soy isoflavone bioavailability. Using a crossover design, chronic soy consumption was compared with soy plus probiotic yogurt or resistant starch in older male and postmenopausal females (n = 31). Isoflavone bioavailability was assessed at the beginning and end of each 5-wk dietary period by sampling plasma and urine after a standardized soy meal. Chronic soy intake did not significantly affect plasma or urinary isoflavones after the soy meal and there were no significant effects of probiotic or resistant starch treatment. However, there were trends for increased circulating plasma daidzein and genistein after the probiotic treatment and for increased plasma daidzein and genistein 24 h after soy intake with resistant starch treatment. Neither treatment induced or increased equol production, although there was a trend for increased plasma equol in "equol-positive" subjects (n = 12) after probiotic treatment. The weak or absence of effects of probiotic yogurt or resistant starch supplement to a chronic soy diet suggests that gut microflora were not modified in a manner that significantly affected isoflavone bioavailability or metabolism.


Methamphetamine abuse, HIV infection, and neurotoxicity.
Methamphetamine (Meth) use and human immunodeficiency virus (HIV) infection are major public health problems in the world today. Ample evidence indicates that HIV transfection risk is greatly enhanced with Meth use. Studies have shown that both HIV infection and Meth abuse can cause neuronal injury leading to neurodegeneration. While many studies have focused on the individual effects of Meth and HIV on the brain, few investigations have been carried out on their co-morbid effect in the nervous system. In this review, we try to summarize recent progress on individual effects of Meth and HIV on neurodegeneration and their potential underlying mechanisms, in addition to exploring their co-morbid effect on the brain.


Endodontic Surgery of a Deviated Premolar Root in the Surgical Orthodontic Management of an Impacted Maxillary Canine.
Maxillary canine impactions are of multifactorial etiology. The incidence of maxillary canine impaction ranges from 1% to 4%. One of the reasons for canine impaction might be a deviated premolar root. This report describes surgical-orthodontic extrusion of an upper canine that occurred only after the endodontic surgery treatment of the adjacent deviated premolar root. Orthograde endodontic treatment followed by endodontic surgery with retrograde filling of the deviated premolar root was performed to obtain a surgical-orthodontic extrusion of the upper canine. A female patient, aged 15 years, with a class I molar relationship was referred to continue the orthodontic therapy. Although a correct surgical-orthodontic extrusion with adequate anchorage was carried out, the maxillary left canine had not erupted. Radiographic examination showed a deviated palatal root of the adjacent maxillary first premolar in the canine eruption path. Root canal filling followed by endodontic surgery of the first premolar deviated root has led to rapid progression of the canine and its placement in the arch in just 3 months. A multidisciplinary management involving endodontic treatment, endodontic surgery, and surgical-orthodontic extrusion could be considered a successful approach in the maxillary impacted canine cases in which adjacent premolar root is deviated. Long-term radiographic follow-up (6 years) indicated stable periodontal health of the canine and premolar without the presence of root resorption.


Covalent immobilization of lipase, glycerol kinase, glycerol-3-phosphate oxidase & horseradish peroxidase onto plasticized polyvinyl chloride (PVC) strip & its application in serum triglyceride determination.
Reusable biostrip consisting enzymes immobilized onto alkylamine glass beads affixed on plasticized PVC strip for determination of triglyceride (TG) suffers from high cost of beads and their detachments during washings for reuse, leading to loss of activity. The purpose of this study was to develop a cheaper and stable biostrip for investigation of TG levels in serum. A reusable enzyme-strip was prepared for TG determination by co-immobilizing lipase, glycerol kinase (GK), glycerol-3-phosphate oxidase (GPO) and peroxidase (HRP) directly onto plasticized polyvinyl chloride (PVC) strip through glutaraldehyde coupling. The method was evaluated by studying its recovery, precision and reusability. The enzyme-strip showed optimum activity at pH 7.0, 35 o C and a linear relationship between its activity and triolein concentration in the range 0.1 to 15 mM. The strip was used for determination of serum TG. The detection limit of the method was 0.1 mM. Analytical recovery of added triolein was 96 per cent. Within and between batch coefficients of variation (CV) were 2.2 and 3.7 per cent, respectively. A good correlation (r=0.99) was found between TG values by standard enzymic colrimetric method employing free enzymes and the present method. The strip lost 50 per cent of its initial activity after its 200 uses during the span of 100 days, when stored at 4 o C. The nitrating acidic treatment of plasticized PVC strip led to glutaraldehyde coupling of four enzymes used for enzymic colourimetric determination of serum TG. The strip provided 200 reuses of enzymes with only 50 per cent loss of its initial activity. The method could be used for preparation of other enzyme strips also.


Oral language competence, young speakers, and the law.
This paper highlights the forensic implications of language impairment in 2 key (and overlapping) groups of young people: identified victims of maltreatment (abuse and/or neglect) and young offenders. Two lines of research pertaining to oral language competence and young people's interface with the law are considered: 1 regarding investigative interviewing with children as victims or witnesses in the context of serious allegations of sexual abuse, and the other pertaining to adolescent offenders as suspects, witnesses, or victims. The linguistic demands that forensic interviewing places on these young people are also considered. Literature concerning the impact of early maltreatment on early language acquisition is briefly reviewed, as is the role of theory of mind in relation to the requirements of investigative interviewing of children and adolescents. High-risk young people (i.e., those who are subject to child protection orders because of suspected or confirmed maltreatment, and those who are engaged with the youth justice system) face an elevated risk for suboptimal language development but may need to draw on their language skills in high-stakes forensic interviews. Implications for early intervention policy and practice are identified, and the need for greater speech-language pathology advocacy and engagement in forensic interviewing research is emphasized.


Applicability of Scrape Loading-Dye Transfer Assay for Non-Genotoxic Carcinogen Testing.
Dysregulation of gap junction intercellular communication (GJIC) is recognized as one of the key hallmarks for identifying non-genotoxic carcinogens (NGTxC). Currently, there is a demand for in vitro assays addressing the gap junction hallmark, which would have the potential to eventually become an integral part of an integrated approach to the testing and assessment (IATA) of NGTxC. The scrape loading-dye transfer (SL-DT) technique is a simple assay for the functional evaluation of GJIC in various in vitro cultured mammalian cells and represents an interesting candidate assay. Out of the various techniques for evaluating GJIC, the SL-DT assay has been used frequently to assess the effects of various chemicals on GJIC in toxicological and tumor promotion research. In this review, we systematically searched the existing literature to gather papers assessing GJIC using the SL-DT assay in a rat liver epithelial cell line, WB-F344, after treating with chemicals, especially environmental and food toxicants, drugs, reproductive-, cardio- and neuro-toxicants and chemical tumor promoters. We discuss findings derived from the SL-DT assay with the known knowledge about the tumor-promoting activity and carcinogenicity of the assessed chemicals to evaluate the predictive capacity of the SL-DT assay in terms of its sensitivity, specificity and accuracy for identifying carcinogens. These data represent important information with respect to the applicability of the SL-DT assay for the testing of NGTxC within the IATA framework.


Excretion of aflatoxin M1 in milk of dairy ewes treated with different doses of aflatoxin B1.
Two experiments were conducted to study the amount of aflatoxin M1 (AFM1) in milk in response to feeding aflatoxin B1 (AFB1). In experiment 1, four dairy ewes in early lactation received a single dose of pure AFB1 (2 mg). Individual milk samples were collected during the following 5 d to measure AFM1 concentration. The average excretion of AFM1 in milk followed an exponential decreasing pattern, with two intermediate peaks at 24 and 48 h. No AFM1 was detected in milk at 96 h after dosing. The mean rate of transfer of AFB1 into AFM1 in milk was 0.032%, with a high individual variability (SD = 0.017%). In experiment 2, 16 dairy ewes in midlactation were divided into four groups that received different daily doses of AFB1 (0, 32, 64, and 128 microgram for control and groups T1, T2, and T3, respectively) for 14 d. Pure AFB1 was administered to each animal divided in two daily doses. Individual milk samples were collected at 12, 24, 36, 48, 72, 96, 144, 216, and 312 h after the first AFB1 administration, during the intoxication period, and every 24 h for 7 d after the withdrawal of AFB1. AFM1 was detected in the milk of all animals of the treated groups at 12 h after the administration of AFB1. In all treated groups, milk AFM1 concentration increased from 12 to 144 h after the beginning of administration. It then decreased, reaching a stable concentration at 216 and 312 h after the first administration. No AFM1 was detected in milk 3 d after the last administration of AFB1. Milk AFM1 concentration measured at steady-state condition was significantly affected by the AFB1 dose (0.031, 0.095, and 0.166 in T1, T2, and T3 groups, respectively), with a linear relationship between AFB1 dose and milk AFM1 concentration (R2 = 77.2%). The carryover (AFM1/AFB1 ratio) was not significantly affected by treatment, and its mean value was 0.112% (SE = 0.011). The carryover was lower than that reported for dairy cattle and goats, suggesting a better ability of sheep to degrade AFB1.


Bacteriophage P4 sut1: a mutation suppressing transcription termination.
In the Escherichia coli satellite phage P4, transcription starting from PLE is prevalently controlled via premature termination at several termination sites. We identified a spontaneous mutation, P4 sut1 (suppression of termination), in the natural stop codon of P4 orf151 that, by elongating translation, suppresses transcription termination at the downstream t151 site. Both the translational and the transcriptional profile of P4 sut1 differed from those of P4 wild-type. First of all, P4 sut1 did not express Orf151, but a higher molecular mass protein, compatible with the 303 codon open reading frame generated by the fusion of orf151, cnr and the intervening 138 nt. Moreover, after infection of E. coli, the mutant expressed a very low amount of the 1.3 and 1.7 kb transcripts originating at PLE and PLL promoters, respectively, and terminating at the intracistronic t151 site, whereas correspondingly higher amounts of the 4.1 and 4.5 kb RNAs arising from the same promoters and covering the entire operon were detected. Thus the sut1 mutation converts a natural stop codon into a sense codon, suppresses a natural intracistronic termination site and leads to overexpression of the downstream cnr and alpha genes. This correlates with the inability of P4 sut1 to propagate in the plasmid state. By cloning different P4 DNA fragments, we mapped the t151 transcription termination site within the 7633-7361 region between orf151 and gene cnr. A potential stem-loop structure, resembling the structure of a Rho-independent termination site, was predicted by mfold sequence analysis at 7414-7385.


A Pilot Remote Curriculum to Enhance Resident and Medical Student Understanding of Machine Learning in Healthcare.
Despite the expanding role of machine learning (ML) in health care and patient expectations for clinicians to understand ML-based tools, few for-credit curricula exist specifically for neurosurgical trainees to learn basic principles and implications of ML for medical research and clinical practice. We implemented a novel, remotely delivered curriculum designed to develop literacy in ML for neurosurgical trainees. A 4-week pilot medical elective was designed specifically for trainees to build literacy in basic ML concepts. Qualitative feedback from interested and enrolled students was collected to assess students' and trainees' reactions, learning, and future application of course content. Despite 15 interested learners, only 3 medical students and 1 neurosurgical resident completed the course. Enrollment included students and trainees from 3 different institutions. All learners who completed the course found the lectures relevant to their future practice as clinicians and researchers and reported improved confidence in applying and understanding published literature applying ML techniques in health care. Barriers to ample enrollment and retention (e.g., balancing clinical responsibilities) were identified. This pilot elective demonstrated the interest, value, and feasibility of a remote elective to establish ML literacy; however, feedback to increase accessibility and flexibility of the course encouraged our team to implement changes. Future elective iterations will have a semiannual, 2-week format, splitting lectures more clearly between theory (the method and its value) and application (coding instructions) and will make lectures open-source prerequisites to allow tailoring of student learning to their planned application of these methods in their practice and research.


The Pull-Through Technique: A Viable Option for Preserving the Inferior Alveolar Nerve during Surgical Resection.
The aim of this study was to present a new surgical technique used to remove benign mandibular tumors with minimal damage to the inferior alveolar nerve. The pull-through technique was shown using an ameloblastoma surgical resection as an example. This technique consisted in the reconstruction of the lower jaw associating the resection of the lesion with nerve repair at the same surgical time. The resection was performed using the pull-through technique and the inferior alveolar nerve was preserved. After 6 months, the patient presented a recovery of approximately 80% of sensory function. The surgical technique presented should be considered an important method by which to produce a higher functional outcome to remove benign mandibular tumors with minimal damage to the inferior alveolar nerve and allows the maintenance of quality of life for the patient, as the consequences of this type of surgery are minimized.


Threshold Knot Selection for Large-Scale Spatial Models With Applications to the Deepwater Horizon Disaster.
Large spatial datasets are typically modeled through a small set of knot locations; often these locations are specified by the investigator by arbitrary criteria. Existing methods of estimating the locations of knots assume their number is known a priori, or are otherwise computationally intensive. We develop a computationally efficient method of estimating both the location and number of knots for spatial mixed effects models. Our proposed algorithm, Threshold Knot Selection (TKS), estimates knot locations by identifying clusters of large residuals and placing a knot in the centroid of those clusters. We conduct a simulation study showing TKS in relation to several comparable methods of estimating knot locations. Our case study utilizes data of particulate matter concentrations collected during the course of the response and clean-up effort from the 2010 Deepwater Horizon oil spill in the Gulf of Mexico.


Moxibustion as an adjunctive treatment for rheumatoid arthritis and its effects on the serum levels of SOST and β-catenin.
To observe the clinical efficacy of moxibustion as an adjunctive treatment for rheumatoid arthritis (RA) based on conventional medication and its effects on serum sclerostin (SOST) and β-catenin levels, exploring the potential mechanisms by which moxibustion may protect joint bones in RA patients. Seventy-six RA patients were randomly divided into an observation group (38 cases, 3 cases dropped out) and a control group (38 cases, 4 cases were eliminated, 2 cases dropped out). The patients in the control group were treated with conventional oral medication; based on the treatment of the control group, the patients in the observation group were treated with moxibustion. The direct moxibustion was applied at Zusanli (ST 36) on both sides and ashi points around small joints, and indirect moxibustion was applied at Shenshu (BL 23) on both sides and ashi points around large joints. The treatment was given three times a week for a total of 5 weeks. The count of pain and swollen joint, morning stiffness score, disease activity score of 28 joints (DAS28), visual analogue scale (VAS) score, health assessment questionnaire (HAQ) score, and serum levels of SOST, β-catenin, and tumor necrosis factor-α (TNF-α) were evaluated before and after treatment in the two groups. Compared those before treatment, after treatment, both groups showed a reduction in pain and swollen joint count (P<0.01, P<0.05), morning stiffness, DAS28, VAS, and HAQ scores (P<0.01, P<0.05), with the observation group having lower scores than the control group (P<0.01). Serum levels of SOST, β-catenin, and TNF-α after treatment in the observation group were lower than those in both before treatment and the control group (P<0.01, P<0.05). There was a positive correlation between the difference in serum β-catenin levels before and after treatment and the difference in serum SOST (r=0.578, P<0.001) and TNF-α (r=0.403, P<0.05) levels in the observation group. In addition to medication, moxibustion as an adjunctive treatment could significantly alleviate joint pain and reduce disease activity in RA patients, suggesting a potential role in joint protection. This mechanism may be related to the inhibition of the inflammatory factor TNF-α, regulation of β-catenin levels, and reduction in the production of the endogenous negative regulator protein SOST within the Wnt/β-catenin signaling pathway.


Enhancing the Activation and Releasing the Brakes: A Double Hit Strategy to Improve NK Cell Cytotoxicity Against Multiple Myeloma.
Natural killer (NK) cells are innate lymphocytes with a strong antitumor ability. In tumor patients, such as multiple myeloma (MM) patients, an elevated number of NK cells after stem cell transplantation (SCT) has been reported to be correlated with a higher overall survival rate. With the aim of improving NK cell use for adoptive cell therapy, we also addressed the cytotoxicity of patient-derived, cytokine-stimulated NK cells against MM cells at specific time points: at diagnosis and before and after autologous stem cell transplantation. Remarkably, after cytokine stimulation, the patients' NK cells did not significantly differ from those of healthy donors. In a small cohort of MM patients, we were able to isolate autologous tumor cells, and we could demonstrate that IL-2/15 stimulated autologous NK cells were able to significantly improve their killing capacity of autologous tumor cells. With the aim to further improve the NK cell killing capacity against MM cells, we investigated the potential use of NK specific check point inhibitors with focus on NKG2A because this inhibitory NK cell receptor was upregulated following ex vivo cytokine stimulation and MM cells showed HLA-E expression that could even be increased by exposure to IFN-γ. Importantly, blocking of NKG2A resulted in a significant increase in the NK cell-mediated lysis of different MM target cells. Finally, these results let suggest that combining cytokine induced NK cell activation and the specific check point inhibition of the NKG2A-mediated pathways can be an effective strategy to optimize NK cell therapeutic approaches for treatment of multiple myeloma.


Evidence for the presence of key chlorophyll-biosynthesis-related proteins in the genus Rubrobacter (Phylum Actinobacteria) and its implications for the evolution and origin of photosynthesis.
Homologs showing high degree of sequence similarity to the three subunits of the protochlorophyllide oxidoreductase enzyme complex (viz. BchL, BchN, and BchB), which carries out a central role in chlorophyll-bacteriochlorophyll (Bchl) biosynthesis, are uniquely found in photosynthetic organisms. The results of BLAST searches and homology modeling presented here show that proteins exhibiting a high degree of sequence and structural similarity to the BchB and BchN proteins are also present in organisms from the high G+C Gram-positive phylum of Actinobacteria, specifically in members of the genus Rubrobacter (R. x ylanophilus and R. r adiotolerans). The results presented exclude the possibility that the observed BLAST hits are for subunits of the nitrogenase complex or the chlorin reductase complex. The branching in phylogenetic trees and the sequence characteristics of the Rubrobacter BchB/BchN homologs indicate that these homologs are distinct from those found in other photosynthetic bacteria and that they may represent ancestral forms of the BchB/BchN proteins. Although a homolog showing high degree of sequence similarity to the BchL protein was not detected in Rubrobacter, another protein, belonging to the ParA/Soj/MinD family, present in these bacteria, exhibits high degree of structural similarity to the BchL. In addition to the BchB/BchN homologs, Rubrobacter species also contain homologs showing high degree of sequence similarity to different subunits of magnesium chelatase (BchD, BchH, and BchI) as well as proteins showing significant similarity to the BchP and BchG proteins. Interestingly, no homologs corresponding to the BchX, BchY, and BchZ proteins were detected in the Rubrobacter species. These results provide the first suggestive evidence that some form of photosynthesis either exists or was anciently present within the phylum Actinobacteria (high G+C Gram-positive) in members of the genus Rubrobacter. The significance of these results concerning the origin of the Bchl-based photosynthesis is also discussed.


Laboratory diagnosis of von Willebrand's disorder: quality and diagnostic improvements driven by peer review in a multilaboratory test process.
Regular multilaboratory surveys of laboratories derived primarily from Australia, New Zealand and Southeast Asia have been conducted over the past 7 years to evaluate testing proficiency in the diagnosis of von Willebrand's disorder (VWD) and to assess changes to test practice. Participating laboratories (currently 45) are asked to perform their usual panel of tests for VWD, and then to self-interpret test results as to the likelihood (or not) of VWD, as well as to the potential subtype identified. Samples provided in the past two survey distributions (both conducted in 2003) were as follows. Survey part A/distribution 1: Normal donor plasma, plasma with borderline normal/reduced levels of VWF (x2) and plasma from an individual with type 2 A VWD. Survey part B/distribution 2 (family VWD study): Plasma from a father, mother and son with borderline normal/reduced von Willebrand factor (VWF), and a daughter with type 3 VWD. In line with previously published survey results, the interassay and within method coefficients of variation (CV) were similar for all assays (around 15-25%), although tending to be slightly higher for VWF:RCo and VWF:CB than VWF:Ag and FVIII:C. Most laboratories reported test values consistent with expected findings, and made correct interpretations or predictions regarding the nature of the samples, although discrepant assay results or interpretations are still seen in approximately 5-10% of responses (typically from laboratories using a more limited test panel or not performing the VWF:CB). Overall, problems with the non-identification of functional VWF discordance in type 2 VWD, the misidentification of functional VWF discordance in type 1 VWD, and difficulties in discriminating types 1 and 3 VWD appear to predominate. In comparison with previous surveys, performance of electro-immuno diffusion (EID) (or Laurel gel) procedures has now ceased, and a reduction in VWF:RCo and VWF:Multimer testing and an increase in latex immunoassay (LIA) testing is sustained. We conclude that laboratories are generally proficient in tests for VWD, and that diagnostic error rates are reduced when test panels are more comprehensive and include the VWF:CB.


Factors influencing referral decisions in physiatry.
As the population ages and more emphasis is placed on patient management than on curative exercise, physical medicine gains an important place in medical specialties. This study investigates the referral behavior in physiatry and compares it with referrals to other specialties. From a sample of 159 primary care physicians in the St. Louis metropolitan area who have a high probability of using physical medicine and rehabilitation, a referral model in physiatry was constructed. The results indicate that while the traditional determinants of referral decision play a significant role in influencing the referral behavior in physiatry, there also is a group of variables in physiatry that are significantly different from those of other subspecialties in determining referral process.


Photoproduction of π0 mesons off neutrons in the nucleon resonance region.
Precise angular distributions have been measured for the first time for the photoproduction of π0 mesons off neutrons bound in the deuteron. The effects from nuclear Fermi motion have been eliminated by a complete kinematic reconstruction of the final state. The influence of final-state-interaction effects has been estimated by a comparison of the reaction cross section for quasifree protons bound in the deuteron to the results for free protons and then applied as a correction to the quasifree neutron data. The experiment was performed at the tagged photon facility of the Mainz Microtron MAMI with the Crystal Ball and TAPS detector setup for incident photon energies between 0.45 and 1.4 GeV. The results are compared to the predictions from reaction models and partial-wave analyses based on data from other isospin channels. The model predictions show large discrepancies among each other and the present data will provide much tighter constraints. This is demonstrated by the results of a new analysis in the framework of the Bonn-Gatchina coupled-channel analysis which included the present data.


Association of the Cylin D1 G870A polymorphism with laryngeal cancer: are they really related?
Cylin D1(CCDN1) is an important regulator of the cell cycle whose alterations are thought to be involved in cancer development. There have been many studies indicating CCDN1 amplification or over- expression in a variety of cancer types. In addition to gene amplification, the G870A polymorphism may be related with altered CCDN1 activity, and therefore with cancer development. This hypothesis has been tested in different cancer types but results have been contradictory. We therefore aimed to investigate any relationship between CCDN1 A870G genotypes and laryngeal squamous cell cancer development and progression. A total of 68 Turkish patients with primary laryngeal squamous cell cancer and 133 healthy controls were enrolled. Polymerase chain reaction-restriction fragment length polymorphism analysis was used to determine the CCDN1 genotypes. No significant association was detected between CCDN1 genotypes and laryngeal squamous cell cancer (LxSCCa) development. Similarly CCDN1 genotypes were not related to clinical parameters of Lx SCCa. However, there was a very significant association between CCDN1 G allele and presence of perineural invasion (p= 0.003; OR: 1.464; CI% 1.073-1.999). CCDN1 G allele frequency was significantly higher in the individuals with perineural invasion (85.7%) when compared to those without (58.5%). The 2 patients who died of disease were both found to possess the GG genotype. These results pose a controversy in suggesting a protective role of the G allele against LxSCCa development and support the association of CCDN1 gene GG genotype with mortality in patients with LxSCCa.


Introduction. Cultural transmission and the evolution of human behaviour.
The articles in this theme issue seek to understand the evolutionary bases of social learning and the consequences of cultural transmission for the evolution of human behaviour. In this introductory article, we provide a summary of these articles (seven articles on the experimental exploration of cultural transmission and three articles on the role of gene-culture coevolution in shaping human behaviour) and a personal view of some promising lines of development suggested by the work summarized here.


VisANT: an integrative framework for networks in systems biology.
The essence of a living cell is adaptation to a changing environment, and a central goal of modern cell biology is to understand adaptive change under normal and pathological conditions. Because the number of components is large, and processes and conditions are many, visual tools are useful in providing an overview of relations that would otherwise be far more difficult to assimilate. Historically, representations were static pictures, with genes and proteins represented as nodes, and known or inferred correlations between them (links) represented by various kinds of lines. The modern challenge is to capture functional hierarchies and adaptation to environmental change, and to discover pathways and processes embedded in known data, but not currently recognizable. Among the tools being developed to meet this challenge is VisANT (freely available at http://visant.bu.edu) which integrates, mines and displays hierarchical information. Challenges to integrating modeling (discrete or continuous) and simulation capabilities into such visual mining software are briefly discussed.


Ferroptosis: potential targets and emerging roles in pancreatic diseases.
Ferroptosis is a newly discovered form of regulatory cell death characterized by excessive iron-dependent lipid peroxidation. In the past decade, significant breakthroughs have been made in comprehending the features and regulatory mechanisms of ferroptosis, and it has been confirmed that ferroptosis plays a pivotal role in the pathophysiological processes of various diseases, including tumors, inflammation, neurodegenerative diseases, and infectious diseases. The pancreas, which is the second largest digestive gland in the human body and has both endocrine and exocrine functions, is a vital organ for controlling digestion and metabolism. In recent years, numerous studies have confirmed that ferroptosis is closely related to pancreatic diseases, which is attributed to abnormal iron accumulation, as an essential biochemical feature of ferroptosis, is often present in the pathological processes of various pancreatic exocrine and endocrine diseases and the vulnerability of the pancreas to oxidative stress stimulation and damage. Therefore, comprehending the regulatory mechanism of ferroptosis in pancreatic diseases may provide valuable new insights into treatment strategies. In this review, we first summarize the hallmark features of ferroptosis and then analyze the exact mechanisms by which ferroptosis is precisely regulated at multiple levels and links, including iron metabolism, lipid metabolism, the GPX4-mediated ferroptosis defense system, the GPX4-independent ferroptosis defense system, and the regulation of autophagy on ferroptosis. Finally, we discuss the role of ferroptosis in the occurrence and development of pancreatic diseases and summarize the feasibility and limitations of ferroptosis as a therapeutic target for pancreatic diseases.


Hazard assessment of oil spills along the main shipping lane in the Red Sea.
This study investigates the risk from oil spills along the main shipping lane in the Red Sea based upon oil spill model trajectories forced by the outputs of validated high resolution regional met-ocean data. Following the intra-annual variations in the met-ocean conditions, the results are presented by classifying the basin into three regions: northern, central and southern Red Sea. The maximum distance traveled by the slick is presented for 1, 2, 5, 10, 14 and 20 days after the commencement of a spill. Different measures of hazard assessment in terms of the concentration of beached oil alongside the corresponding probability maps are also analyzed. The volume fractions of beached, dispersed and evaporated oil, 20 days after the commencement of a spill are quantified. The Red Sea general circulation is characterized by rich mesoscale eddies, which appear to be the most prevailing dynamics in oil transport in the basin. Two case events are analyzed to closely examine the effects of the mesoscale circulations on the fate of spilled oil. The results of this study provide a comprehensive assessment of oil spill hazards in the Red Sea, stemming its main shipping lane and identifies the areas at high risk that require timely mitigation strategies.


Non-coding RNAs in cardiovascular cell biology and atherosclerosis.
Atherosclerosis underlies the predominant number of cardiovascular diseases and remains a leading cause of morbidity and mortality worldwide. The development, progression and formation of clinically relevant atherosclerotic plaques involves the interaction of distinct and over-lapping mechanisms which dictate the roles and actions of multiple resident and recruited cell types including endothelial cells, vascular smooth muscle cells, and monocyte/macrophages. The discovery of non-coding RNAs (ncRNAs) including microRNAs, long non-coding RNAs, and circular RNAs, and their identification as key mechanistic regulators of mRNA and protein expression has piqued interest in their potential contribution to atherosclerosis. Accruing evidence has revealed ncRNAs regulate pivotal cellular and molecular processes during all stages of atherosclerosis including cell invasion, growth, and survival; cellular uptake and efflux of lipids, expression and release of pro- and anti-inflammatory intermediaries, and proteolytic balance. The expression profile of ncRNAs within atherosclerotic lesions and the circulation have been determined with the aim of identifying individual or clusters of ncRNAs which may be viable therapeutic targets alongside deployment as biomarkers of atherosclerotic plaque progression. Consequently, numerous in vivo studies have been convened to determine the effects of moderating the function or expression of select ncRNAs in well-characterized animal models of atherosclerosis. Together, clinicopathological findings and studies in animal models have elucidated the multifaceted and frequently divergent effects ncRNAs impose both directly and indirectly on the formation and progression of atherosclerosis. From these findings' potential novel therapeutic targets and strategies have been discovered which may pave the way for further translational studies and possibly taken forward for clinical application.


Physical Activity, Screen-Based Sedentary Behavior, and Sleep Duration in Adolescents: Youth Risk Behavior Survey, 2011-2013.
This study examined the concurrent associations of physical activity and screen-based sedentary behavior with sleep duration among adolescents by using data from the national Youth Risk Behavior Survey 2011-2013. Using latent class analysis, we identified 4 latent subgroups of adolescents with various levels of physical activity and screen-based sedentary behavior. The subgroup with high levels of physical activity and low levels of sedentary behavior generally showed greater odds of having sufficient sleep (≥8 hours/night) than the other subgroups. Findings imply that concurrent achievement of a high level of physical activity and low level of screen-based sedentary behavior is necessary to promote sufficient sleep among adolescents.


Identification of novel classes of protein kinase inhibitors using combinatorial peptide chemistry based on functional genomics knowledge.
A discovery approach based on an intramolecular inhibitory mechanism was applied to a prototype calmodulin (CaM)-regulated protein kinase in order to demonstrate a proof-of-principle for the development of selective inhibitors. The overall approach used functional genomics analysis of myosin light chain kinase (MLCK) to identify short autoinhibitory sequences that lack CaM recognition activity, followed by recursive combinatorial peptide library production and comparative activity screens. Peptide 18 (Arg-Lys-Lys-Tyr-Lys-Tyr-Arg-Arg-Lys-NH2), one of several selective inhibitors discovered, has an IC50 = 50 nM for MLCK, inhibits CaM kinase II only at 4000-fold higher concentrations, and does not inhibit cyclic AMP-dependent protein kinase. Analogues of peptide 18 containing conformationally constrained cis-4-aminocyclohexanecarboxylic acid retained affinity and selectivity. The inhibitors add to the armamentarium available for the deconvolution of complex signal transduction pathways and their relationship to homeostasis and disease, and the approach is potentially applicable to enzymes in which the catalytic and regulatory domains are found within the same open reading frame of a cDNA.


Sarcoidosis and reactive pulmonary hypertension.
Despite diffuse disease of the lungs (often with widespread inflammation or obliteration of blood vessels) in sarcoidosis, pulmonary hypertension is uncommon, occurring in 1% to 4% of cases. We report a case of sarcoidosis and severe pulmonary hypertension that, in striking contrast to other reports, occurred in the absence of obliterative pulmonary vascular disease. We therefore examined the possibility of whether an abnormality in pulmonary vascular tone might be a cause of the pulmonary hypertension. In pharmacologic studies, we demonstrated pulmonary vasodilatation and, in response to increased pulmonary blood flow, the elaboration of the pulmonary vasoconstricting eicosanoid, thromboxane.


An efficient selection producing structural gene mutants of yeast alcohol dehydrogenase resistant to pyrazole.
Selection for resistance to allyl alcohol in respiration-incompetent Saccharomyces cerevisiae produces a high proportion of mutants that can be localized within the ADH2 structural gene and that still, because of the type of selection employed, retain enzyme activity. We show here that a similar type of selection produces a similarly high proportion of mutants resistant to the competitive inhibitor pyrazole. The first four mutants examined, picked at random from a collection of spontaneous pyrazole-resistant mutants, show altered--usually increased--KM values for ethanol and NAD+, and markedly increased K1 values for pyrazole, compared with the wild type. When these kinetic measures and their electrophoretic mobilities were compared, all the mutants could be clearly distinguished from each other as well as from wild type. Genetic analysis shows these mutants to be close to and probably resident in the structural gene. For a variety of reasons, these mutants are even more favorable subjects for population genetic analysis and the dissection of molecular microevolution than are allyl alcohol-resistant mutants.


A practical method of serial bedside measurement of cerebral blood flow and metabolism during neurointensive care.
Acute encephalopathy is a major cause of death and neurological handicap in children. The principle aims of treatment are to provide adequate cerebral blood flow for the brain's metabolic needs and to prevent intracranial pressure rising above the level at which brain herniation occurs. Rational management requires an understanding of the pathophysiological changes in cerebral blood flow and metabolism which occur. The paucity of data on this subject reflects the perceived difficulty of measuring cerebral blood flow and cerebral metabolism in children. A modification of the Kety Schmidt technique of measuring cerebral blood flow and cerebral metabolism is described. This modification makes it possible to perform serial bedside measurements in children receiving intensive care. This method was used to perform 348 measurements in 58 children. The method was reproducible and no significant complications were encountered. The results indicated that appreciable changes in cerebral blood flow and metabolism could occur in individual patients over time, emphasising the importance of serial measurements. This technique may provide a practical means of monitoring cerebral blood flow and metabolism in very sick children receiving neurointensive care and evaluating the efficacy of treatment.


[New Helicobacter pylori Eradication Therapies].
While the prevalence of Helicobacter pylori (H. pylori) infection is decreasing in Korea, the incidence of gastric cancer remains high, emphasizing the importance of H. pylori eradication. A new treatment strategy is needed as the eradication rate with standard triple therapy, which is currently the standard first-line regimen for H. pylori infection, has decreased below the optimum level. The major cause of eradication failure is increased antibiotic resistance. Sequential, concurrent, and hybrid therapies that include clarithromycin produce higher eradication rates than conventional standard triple therapy. However, the effectiveness of these treatments is limited in regions where the resistance rate to various antibiotics is high. Bismuth quadruple therapy is another alternative therapy, but again the eradication rate is not sufficiently high. Tailored therapy based on individual characteristics, including antibiotic susceptibility, may be ideal, but there are several limitations for clinical application and further research is needed. New potassium-competitive acid blocker-based therapies could emerge as effective alternatives in the near future. A consensus is needed to establish a strategy for applying new eradication therapies in Korea.


[Significance of video-assisted thoracoscopy in diagnosis of disseminated pulmonary processes of obscure etiology].
The experience of diagnosis of disseminated pulmonary processes (DPP) of obscure etiology using videothoracoscopy (VTS) and video-assisted operations is presented. The methods of VTS operations using endostaplers Endopath and UO-40 apparatuses are depicted; a comparative characteristic of various kinds of VTS is adduced. Application of endostaplers Endopath had permitted to shorten th patients stationary treatment duration and to omit postoperative pain syndrome. Low invasiveness and high efficacy of VTS while doing the DPP etiology verification and for the patients postoperative rehabilitation shortening were noted


Resilience in Cancer Patients.
Background: Being diagnosed with cancer and undergoing its treatment are associated with substantial distress that can cause long-lasting negative psychological outcomes. Resilience is an individual's ability to maintain or restore relatively stable psychological and physical functioning when confronted with stressful life events and adversities. Posttraumatic growth (PTG) can be defined as positive life changes that result from major life crises or stressful events. Objectives: The aims of this study were to 1) investigate which factors can strengthen or weaken resilience and PTG in cancer patients and survivors; 2) explore the relationship between resilience and PTG, and mental health outcomes; and 3) discuss the impact and clinical implications of resilience and PTG on the process of recovery from cancer. Methods: A literature search was conducted, restricted to PubMed from inception until May 2018, utilizing the following key words: cancer, cancer patients, cancer survivors, resilience, posttraumatic growth, coping, social support, and distress. Results: Biological, personal, and most importantly social factors contribute to cancer patients' resilience and, consequently, to favorable psychological and treatment-related outcomes. PTG is an important phenomenon in the adjustment to cancer. From the literature included in this review, a model of resilience and PTG in cancer patients and survivors was developed. Conclusions: The cancer experience is associated with positive and negative life changes. Resilience and PTG are quantifiable and can be modified through psychological and pharmacological interventions. Promoting resilience and PTG should be a critical component of cancer care.


Kinematic and kinetic comparisons between American and Korean professional baseball pitchers.
The purpose of this study was to quantify and compare kinematic, temporal, and kinetic characteristics of American and Korean professional pitchers in order to investigate differences in pitching mechanics, performance, and injury risks among two different cultures and populations of baseball pitchers. Eleven American and eight Korean healthy professional baseball pitchers threw multiple fastball pitches off an indoor throwing mound positioned at regulation distance from home plate. A Motion Analysis three-dimensional automatic digitizing system was used to collect 200 Hz video data from four electronically synchronized cameras. Twenty kinematic, six temporal, and 11 kinetic variables were analyzed at lead foot contact, during the arm cocking and arm acceleration phases, at ball release, and during the arm deceleration phase. A radar gun was used to quantify ball velocity. At lead foot contact, the American pitchers had significantly greater horizontal abduction of the throwing shoulder, while Korean pitchers exhibited significantly greater abduction and external rotation of the throwing shoulder. During arm cocking, the American pitchers displayed significantly greater maximum shoulder external rotation and maximum pelvis angular velocity. At the instant of ball release, the American pitchers had significantly greater forward trunk tilt and ball velocity and significantly less knee flexion, which help explain why the American pitchers had 10% greater ball velocity compared to the Korean pitchers. The American pitchers had significantly greater maximum shoulder internal rotation torque and maximum elbow varus torque during arm cocking, significantly greater elbow flexion torque during arm acceleration, and significantly greater shoulder and elbow proximal forces during arm deceleration. While greater shoulder and elbow forces and torques generated in the American pitchers helped generate greater ball velocity for the American group, these greater kinetics may predispose this group to a higher risk of shoulder and elbow injuries.