Elevated body mass index is associated with lower serum anti-mullerian hormone levels in infertile women with diminished ovarian reserve but not with normal ovarian reserve.
To investigate the association between elevated body mass index (BMI) and ovarian reserve. Cross-sectional study. Academic institutions. Two hundred ninety women with infertility. Diminished ovarian reserve (DOR) was defined as day 3 FSH>10 IU/L. None. Random serum antimullerian hormone (AMH) levels and number of oocytes retrieved during assisted reproductive technology cycle. Increasing BMI was associated with lower random serum AMH levels in infertile women with DOR but not in women with normal ovarian reserve (NOR). Among women with DOR, mean random serum AMH levels were 33% lower in overweight and obese women compared with women with normal weight. The same association was not true for women with NOR. Out of 290 women evaluated for infertility, 109 women underwent a controlled ovarian hyperstimulation (COH)-IVF cycle. Women with elevated BMI and DOR had lower number of oocytes retrieved compared with women with normal BMI and DOR (6.4±4.3 vs. 9.4±6), an association that was not observed among women with NOR. Overweight and obese women with DOR as defined by high day 3 serum FSH levels have lower serum AMH levels and number of oocytes retrieved compared with nonobese women with DOR.


Computed tomographic detection of intestinal calcification of Schistosomiasis japonica.
The authors report 4 cases of intestinal calcification detected by computed tomography in patients with Schistosomiasis japonica. The calcification was present in the duodenum in 1 and in the rectum and/or colon in 3.


Functional constraints of 6-phosphogluconate dehydrogenase (6-PGD) based on sequence and structural information.
The pentose phosphate cycle is considered as a major source of NADPH and pentose needed for nucleic acid biosynthesis. 6-Phosphogluconate dehydrogenase (6PGD), an enzyme participating in this cycle, catalyzes the oxidative decarboxylation of 6PGD to ribulose 5-phosphate with the subsequent release of CO2 and the reduction of NADP. We have determined the amino acid sequence of 6PGD of Bactrocera oleae and constructed a three-dimensional model based on the homologous known sheep structure. In a comparative study of 6PGD sequences from numerous species, all the conserved and variable regions of the enzyme were analyzed and the regions of functional importance were localized, in an attempt promoted also by the direct involvement of the enzyme in various human diseases. Thus, analysis of amino acid variability of 37 6PGD sequences revealed that all regions important for the catalytic activity, such as those forming the substrate and coenzyme binding sites, are highly conserved in all species examined. Moreover, several amino acid residues responsible for substrate and coenzyme specificity were also found to be identical in all species examined. The higher percentage of protein divergence is observed at two regions that accumulate mutations, located at the distant parts of the two domains of the enzyme with respect to their interface. These peripheral regions of non-functional importance are highly variable and are predicted as antigenic, thus reflecting possible regions for antibody recognition. Furthermore, locating the differences between diptera 6PGD sequences on the three-dimensional model suggests probable positions of different amino acid residues appearing at B. oleae fast, intermediate, and slow allozymic variants.


DDT residues in cod livers from the Maritime Provinces of Canada.
The residues of DDT and its analogs were estimated in a number of cod liver samples (Gadus morhua) collected at six sampling sites off the Atlantic Coast of the Maritime Provinces of Canada during the summer of 1971. The residue levels indicated widespread distribution of DDT over the entire region sampled. Variations in the relative contributions of p,p'-DDE and p,p'-DDT to the total DDT residues (xiDDT) were noted and the tendency for these residues to preferentially accumulate in lipid rich tissues was demonstrated. The residue levels found in cod livers were compared to the residue levels determined in cod flesh taken from some of the same specimens and also to residue levels in commercially refined cod liver oils. Samples of each of these types were stored at -29 degrees C and analyzed in 1973 for DDT and PCB simultaneously. The xiDDT residues determined by both methods of analysis were compared.


Shoulder impingement syndrome: impingement view and arthrography study based on 100 cases.
A prospective evaluation combining the shoulder impingement view and arthrography was made in patients presenting with chronic shoulder pain. Five hundred and twenty-three patients with chronic shoulder pain were X-rayed using conventional views and impingement views. One hundred of these patients (mean age 62 years) had subacromial bony spurs on the impingement view; these underwent arthrography. They were divided into two groups according to the degree of spur formation--whether or not the size of the spur exceeded one half of the acromial width as measured from the outer margin to the acromioclavicular joint. Of the 100 subacromial spurs demonstrated on the impingement view, only 18 were visible on the conventional view as assessed by an independent radiologist. Arthrography showed 35 cases of rotator cuff tear. The size of the bony spur was strongly associated with the incidence of rotator cuff tear (P < 0.02).


Visual Exploration and Observation of Real-Life Interactions Between Children with ASD and Service Dogs.
Two original studies explored relationships between visual attention of children with ASD (candidates for receiving a service dog) and their behaviors during their first interaction with a service dog. The first study consisted in video behavioural analyses of 16 children with ASD interacting with a service dog. During the interaction with a service dog, the time children with ASD spent looking towards social items vs objects was associated with how they interacted with the service dog. The second study was exploratory (i.e. 6 children), using the same behavioural approach but coupled with eye-tracking data. The more children with ASD looked at both their parent and the evaluator, as opposed to inanimate items, the more they interacted with the service dog.


Superoxide radicals and hemorrhagic shock: are intravascular radicals associated with mortality?
Superoxide radicals (SORs) are formed during hemorrhagic shock. However, the association between SOR formation and mortality remains undefined. Would neutralization of SORs during shock improve survival? Superoxide dismutase (SOD) was covalently linked to Ficoll to prolong vascular persistence and ensure ongoing neutralization of intravascular SORs. Six groups of Sprague-Dawley rats were studied. Rats were exsanguinated to a mean arterial pressure of 30 Torr, sustained for 60 min. Ficoll linked superoxide dismutase (SOD-F), 5000 Units + catalase, 150 Units, was suspended in 1 ml of saline and injected following the 60-min hypotensive period. Resuscitation followed for appropriate groups. Pretreated SOD-F rats received a 1-ml bolus prior to exsangination. Pretreatment with SOD-F did not improve survival in non-resuscitated groups despite improvement in vascular circulation (P greater than 0.10, NS). In the standard non-resuscitation group, there is also no improvement (P greater than 0.10, NS). Resuscitation with or without SOD-F significantly alters survival rates (P less than 0.025) with respect to non-resuscitated controls. However, application of SOD-F in conjunction with resuscitation does not improve survival with respect to resuscitation controls (P greater than 0.10, NS). Although SOD-F has a vascular half-life advantage over SOD, the improvement in survival is statistically non-significant. Intravascular SORs do not appear to be associated with mortality. SOR release and consequent damage to the vasculature may be preceded by a more significant intracellular damage. Intracellular SOR damage and its association with mortality in hemorrhagic shock remains an open issue.


Primary brain lymphoma. A brief review of clinical aspects and management.
Primary C.N.S. lymphoma is a rare tumor. Five such cases were treated in our clinic between January, 1991, and October, 1993. Four patients had tumor decompression and one had total resection. All of them received radiotherapy (radiation dose 40 Gy) and chemotherapy. One patient expired during the immediate postoperative period. Four patients showed a disappearance of the tumor on CT scan after the complete course of therapy of 9 months. Three patients showed recurrence intracranially at 15, 12, and 10 months. All patients died during follow up except one, who has been alive without recurrence for 10 months. Median survival was 13 months.


The effect of bariatric surgery on adipocytokines, renal parameters and other cardiovascular risk factors in severe and very severe obesity: 1-year follow-up.
To evaluate the effect of weight loss after bariatric surgery (BS) on peripheral adipocytokines, renal parameters and other cardiovascular risk factors (CVRFs). A total of 70 (41 women) extremely obese adults were prospectively studied before and 12 months after surgery. 24 (15 women) normal-weight adults. Anthropometric, biochemical and renal parameters were recorded. Presurgery, adiponectin (ADPN) was lower, whereas leptin, insulin resistance, C-reactive protein, creatinine clearance and albuminuria were higher in patients than controls (P<0.001). All parameters improved postsurgery. Changes in ADPN correlated negatively with leptin, insulin resistance, albumin, C-reactive protein, and creatinine clearance. Multiple regression analysis: using changes in ADPN as the dependent variable, only changes in insulin resistance (P=0.005) and albumin (P=0.019) were significant independent determinants for changes in ADPN. No statistical differences were found in relation to the degree of obesity. Patients changed to obesity type I after surgery. This implies a substantial improvement of CVRFs including ADPN, creatinine clearance and albuminuria. Changes in plasma ADPN correlated negatively with insulin resistance and with albuminemia but not with renal parameters. The lack of differences between different degrees of obesity suggests that the relationship between weight and CVRFs no longer exists when obesity becomes very extreme.


Hypercholesterolemia in non-insulin-dependent diabetes mellitus: different effect of simvastatin on VLDL and LDL cholesterol levels.
Non-insulin-dependent diabetes mellitus (NIDDM) is often characterized by an increase in VLDL-triglyceride, VLDL-cholesterol, LDL-cholesterol and a reduction in HDL-cholesterol. HMG-CoA reductase inhibitors significantly lower cholesterol rates and have an indirect effect on the LDL receptor. We measured the effect of simvastatin in 28 hypercholesterolemic subjects, including 14 with NIDDM in good metabolic control (HbAIc 7.8% +/- 1.3%). A 24-week treatment with 10 mg/day (weeks 1-4), 20 mg/day (weeks 5-8) and 40 mg/day (weeks 9-24) simvastatin revealed different responses in diabetic and non-diabetic patients. Total cholesterol, LDL-cholesterol and apo B decreased significantly in both groups (less in the diabetics), whereas only NIDDM patients displayed a significant reduction in VLDL-cholesterol and VLDL-apo B. In the non-diabetics, the reduction in plasma cholesterol was mainly confined to the LDL fraction (276 +/- 65 vs. 132 +/- 28 mg/dl), whereas a significant fall in VLDL-cholesterol (45 +/- 19 vs. 21 +/- 10 mg/dl) was more evident in the NIDDM patients. Simvastatin also influenced plasma apo B levels (221 +/- 33 vs 134 +/- 23 mg/dl in non-diabetics and 182 +/- 44 vs. 134 +/- 30 mg/dl in diabetics). Significant reduction of apo B, LDL-apo B (205 +/- 39 vs. 128 +/- 23 mg/dl) in the non-diabetics and VLDL-apo B (16 +/- 5 vs. 9 +/- 2 mg/dl) in the diabetics, indicates that the VLDL are primarily concerned when statins are administered in NIDDM.(ABSTRACT TRUNCATED AT 250 WORDS)


Study on the association between environmental cadmium exposure, cytochrome P450-mediated 20-HETE, heme-oxygenase-1 polymorphism and hypertension in Thai population residing in a malaria endemic areas with cadmium pollution.
The aims of the study were to investigate (i) the effects of environmental cadmium (Cd) on hypertension, biological markers of renal dysfunction and renal cytochrome P450-mediated arachidonate metabolism; and (ii) the association between genetic polymorphism of heme oxygenase-1 (HO-1) and hypertension and Cd-induced renal injury in the exposed Thai population. The study was conducted in adult subjects residing in Cd-contaminated malaria endemic areas of Mae Sot District, Thailand. All subjects were randomly selected and consistently distributed for sex, age and residential areas. Blood and urinary Cd levels were not significantly different between the case (hypertensive) and control (matched-pair normotensive) groups. While other renal dysfunction biomarkers were comparable between the two groups, urinary microalbumin, urinary 20-hydroxy-5,8,11,14-eicosatetraenoic acid (20-HETE) and serum creatinine were siginificantly higher in the hypertensive group. Only N-acetyl-β-glucosaminidase (NAG) showed positive correlation with Cd in hypertensive and normotensive group. With respect to heme oxygenase-1 (HO-1) polymorphism, the frequencies of (GT)(n) alleles were similar in both case and control groups. The frequency of SL genotype was significantly higher in the control group, whereas the frequency of ML genotype was significantly higher in the case group. Although no significant difference between 20-HETE and NAG levels in various HO-1 genotypes was found, a trend of increase in 20-HETE and NAG levels was observed in subjects carrying longer (GT)(n) repeats. Results from the present study provide no clear evidence on the direct effects of environmental Cd on high blood pressure development in the non-occupational exposed Thai population. Furthermore, the indirect effect of Cd through HO-1 (genetic polymorphism and prevalence of long GT(n) repeats) and 20-HETE was inconclusive. Based on the data obtained in the present investigation further studies should be performed which use a larger sample size and effectively control for confounding. This should provide more definitive evidence of the relationship between Cd exposure and high blood pressure.


Assessment of muscle-strengthening exercise in public health surveillance for adults: A systematic review.
There is strong scientific evidence that muscle-strengthening exercise (i.e. use of weight machines, push-ups, sit-ups) is independently associated with a reduced risk of multiple chronic diseases (e.g. diabetes, hypertension, cardiovascular disease). However, prevalence rates for meeting the muscle-strengthening exercise guideline (≥2 times/week) are significantly lower (~20%) than those reported to meet the aerobic physical activity guideline (e.g. walking, jogging, cycling) (~50%). It is therefore important to understand public health surveillance approaches to assess muscle-strengthening exercise. The aim of this review was to describe muscle-strengthening exercise assessment in public health surveillance. Informed by the PRISMA guidelines, an extensive keyword search was undertaken across 7 electronic data bases. We identified 86,672 possible articles and following screening (n = 1140 in full-text) against specific inclusion criteria (adults aged ≥18 years, English, studies containing <1000 participants), extracted data from 156 manuscripts. Fifty-eight different survey systems were identified across 17 countries. Muscle-strengthening exercise frequency (85.3%), duration (23.7%) and intensity (1.3%) were recorded. Muscle-strengthening exercise questions varied significantly, with some (11.5%) requiring a singular 'yes' vs 'no' response, while others (7.7%) sought specific details (e.g. muscle groups targeted). Assessments of duration and intensity were inconsistent. Very few studies measured the validity (0.6%) and reliability (1.3%) of muscle-strengthening exercise questions. Discrepancy exists within the current assessment systems/surveys used to assess muscle-strengthening exercise in public health surveillance. This is likely to impede efforts to identify at risk groups and trends within physical activity surveillance, and to accurately assess associations between muscle-strengthening exercise and health-related outcomes.


Transforming growth factor beta 1 expression in the endometrium of the mare during placentation.
In situ hybridization, Northern blotting, and immunohistochemical techniques were used to study the expression of transforming growth factor beta 1 (TGF beta 1) in the endometrium of the mare during the first 150 days of pregnancy (term = 330-340 days). In situ hybridization using an oligonucleotide (45mer) probe, based on a homologous region within all known mammalian TGF beta 1 DNA sequences, demonstrated TGF beta 1 mRNA accumulation in the glandular and lumenal epithelial cells of the endometrium from day 33 onwards which corresponds to the time of implantation (day 33-45). Expression in the endometrium remained at a high level to the end of the sampling period (day 150). There was also marked expression of TGF beta 1 in the mononuclear cells accumulated around the periphery of the specialized trophoblast cells of the endometrial cup within the endometrium and in the mononuclear cells accumulated in the endometrial stroma of mares carrying failing donkey-in-horse pregnancies created by embryo transfer. The sense (control) oligonucleotide probe exhibited no hybridization to any tissue at any stage. Northern blot analysis demonstrated that the oligonucleotide probe and a porcine TGF beta 1 cDNA clone hybridized to a single 2.5 kb transcript in horse endometrial and lymphocyte RNA, thus validating the oligonucleotide probe for detection of horse TGF beta 1 mRNA. Furthermore, both probes demonstrated an increased signal in the pregnant endometrium from day 33 onwards, thereby confirming the in situ hybridization results. Immunostaining with a specific anti-bovine TGF beta 1 serum also showed increasing TGF beta 1 accumulation in endometrial epithelia during pregnancy, and localization of the protein in endometrial stroma and in the trophoblast layer of the placenta after day 60 of pregnancy. These results show that TGF beta 1 expression increases in the maternal endometrium of the mare at the time of implantation and that it may play a role in regulating endometrial and/or trophoblast growth and differentiation during placentation in this species. It may also influence fetal development (via placental transfer) at a later stage of gestation.


Diabetes mellitus and hip fracture: a study of 5966 cases.
Diabetes mellitus, and especially type II diabetes, is a widespread and increasing problem in the western world due to the high rates of obesity. It has also been shown in previous studies that diabetics have impaired fracture healing. The aim of this study was to see exactly what role diabetes plays in hip fracture because it is a partially modifiable disease, and to see whether there are any changes that we could make to our practice to improve patient outcome. We analysed the characteristics and outcomes for 477 hip fracture patients who were known to be diabetic at the time of admission, against 5489 non-diabetic hip fracture patients. At the time of admission the diabetic patients were more likely to be using walking aids [268/477 (56%) versus 2455/5489 (45%), p<0.0001], have a more restricted walking ability and a higher mean ASA grade (2.9 versus 2.6, p<0.0001). Diabetics patients were more likely to develop cardiac post-operative complications [26/477 (5.5%) versus 146/5489 (2.7%), p=0.0008] and to develop pressure ulcers [34/477 (7.1%) versus 171/5489 (3.1%), p<0.0001]. Hospital stay was increased for those with diabetes (25 days versus 21 days, p 0.006). No difference in surgical complications was seen between groups. At one year, recovery of function was similar for diabetic patients compared to those without diabetes. These findings show diabetics are at an increased risk of specific complications and have a longer length of hospital stay but generally make a normal recovery thereafter.


Comparison of in vivo and in vitro RNA synthesis on polytene chromosomes of Drosophila.
A comparative radioautographic study of the RNA precursors incorporation on polytene chromosomes of Drosophila in vivo in the cells of salivary glands, and in vitro during incubation of E.coli RNA polymerase on slides with fixed chromosomes was performed.--The pattern of in vivo 3H-uridine incorporation on different sections of the chromosomes drastically differed from the in vitro 3H-UTP incorporation which seems to be much more related to DNA content of the individual small sections. In both cases puffing of the loci resulted in the increase of RNA synthesis but in vitro only 2-3 fold and in vivo much more. Hence, RNA synthesis in vitro was unspecific and did not reflect the in vivo RNA synthesis.--On the other hand, E.coli RNA polymerase completely mimics in vitro the dosage compensation phenomenon making twice as much RNA on one X-chromosome of males (1X2A) as on each of X-chromosomes of diploid (2X2A) and triploid (3X3A) females and super-females (3X2A), and the intermediate amount of RNA on each of X-chromosomes of intersexes (2X3A). It is suggested that the differences in the in vitro template activity of X-chromosomes of cells with different X:A ratio are due to different extent of condensation of their deoxyribonucleoprotein (DNP). Yet, both male and each of female X-chromosomes bind the same amount of thymus histone FI labelled with fluorochrome which indicates that they contain the same amount of "open" regions with exposed chromosomal DNA accessible to external proteins.--On the basis of these observations a hypothesis is put forward which suggests that RNA transcription in animal chromosomes is regulated at two levels by different mechanisms; the first one controls the extent of condensation of DNP of genetic loci and determines their competence to the second mechanism which involves the action of gene-specific activator proteins. According to this hypothesis the phenomenon of dosage compensation of sex-linked genes is due to decondensation of DNP of male X-chromosome which renders its loci twice as responsive to activators as compared to the same loci in females.


Telomerase reverse transcriptase genetically modified adipose tissue derived stem cells improves erectile dysfunction by inhibiting oxidative stress and enhancing proliferation in rat model.
Erectile dysfunction (ED) is considered to be incapable of obtaining or/and keeping a sufficient erection function to receive the satisfactory during the sexual intercourse. This study aims to investigate the effects of telomerase reverse transcriptase (hTERT) modified adipose tissue derived stem cells (ADSCs) autologously injected into cavernosa of the ED rats on erectile function. The ADSCs were isolated form the rat subcutaneous adipose tissue sample, and identified by examining the CD29 and CD44 molecule. The ED model was established by using 100μg/kg apomorphine (APO). The adenovirus expressing rat hTERT (Ade-hTERT vector) was established, and transfected into ADSCs and injected into ED rat model, respectively. Telomerase activity, cell growth, cell apoptosis were analyzed by using TRAP ELISA assay, CCK8 assay and flow cytometry assay, respectively. The trophic growth factors were examined by using enzyme-linked immunosorbent assay (ELISA). The mRNA and proteins were detected by using semi-quantitative PCR and western blot assay, respectively. Ade-hTERT vector was highly expressed in both ADSCs and ED rat mode. The hTERT expression enhanced the telomerase activity, inhibits cell apoptosis and enhances proliferation of ADSCs (P<0.05). hTERT expression triggers the secretory function of ADSCs and induces differentiative potential of ADSCs. hTERT expression inhibits apoptosis and increases eNOS and nNOS levels in older ED rats compared to the Ade-vector injected ED rats (P<0.05). In conclusion, the hTERT modification could enhance the ADSCs proliferation, and hTERT modified ADSCs could increase the anti-oxidative stress capacity in the ED rat model.


LOCKing in Cellular Potential.
Recently in Nature Genetics, Wen et al. (2009) report that H3K9me2 modification is more abundant in differentiated cells than in embryonic stem cells and that it decorates chromatin in repressive blocks.


Cerebrospinal fluid absorption block at the vertex in chronic hydrocephalus: obstructed arachnoid granulations or elevated venous pressure?
The lack of absorption of CSF at the vertex in chronic hydrocephalus has been ascribed to an elevation in the arachnoid granulation outflow resistance (Rout). The CSF infusion studies measuring Rout are dependent on venous sinus pressure but little is known about the changes in pressure which occur throughout life or with the development of hydrocephalus. Twenty patients with chronic hydrocephalus underwent MR venography and MR flow quantification techniques. The venous outflow pressure was estimated from the sinus blood flow and the cross-sectional area of the transverse sinuses. Adult controls as well as a normal young cohort were selected to estimate the change in sinus pressure which occurs throughout life and following the development of hydrocephalus. Significance was tested with a Student's t-test. The size of the transverse sinuses was unchanged from the 1(st) to the 5(th) decade of life, indicating a stable outflow resistance. However, the blood flow was reduced by 42%, indicating a likely similar reduction in pressure gradient across the sinuses. The sinuses of hydrocephalus patients were 38% smaller than matched controls, indicating a 2.5 times increase in resistance. Despite the 24% reduction in blood flow, a significant increase in sinus pressure is suggested. The size of the venous sinuses normally does not change over the age range investigated but sinus pressure is reduced proportional to an age-related blood flow reduction. Hydrocephalus is associated with much smaller sinuses than normal and an elevation in venous pressure may explain the lack of CSF absorption into the arachnoid granulations in chronic hydrocephalus.


Bidirectional priming in infants.
In associative priming, the direct activation of one concept indirectly activates others that are associated with it, depending on the directionality of the association. We asked whether associative priming in preverbal infants is bidirectional. Infants associated a puppet imitation task with an operant train task by watching an adult model target actions on the puppet in the incidental context of the train. Later, priming of the forgotten memory of the train task reactivated the infants' memory of the puppet task (Experiment 1), and priming of the infants' forgotten memory of the puppet task reactivated their memory of the train task (Experiment 2). The finding that associative priming was bidirectional offers new insights into the nature of the mnemonic networks formed early in infancy. Additionally, the fact that the present association was formed rapidly and incidentally suggests that a fast mapping, general learning mechanism, like that posited to mediate word-object learning, was responsible for its encoding.


Biological characterization of guinea pig lymphotoxin production.
The generation of serum-free lymphotoxin by antigen-stimulated ovalbumin immune strain 2/N guinea pig peritoneal leukocytes in vitro is dependent upon a number of common variables in cell culture. Lymphotoxin production varies directly with antigen concentration, duration of antigen exposure and leukocyte culture, leukocyte density, and medium volume. The maximum concentration of lymphotoxin generated in the medium has a limiting value that is independent of antigen concentration, leukocyte density, and duration of antigen exposure or leukocyte culture, suggesting feedback control of lymphokine production. Optimal conditions for the reproducible maximum generation of guinea pig lymphotoxin were 10(7) oil-induced peritoneal leukocytes from immune animals cultured for 12-24 hr in 20 ml RPMI 1640 medium containing 100 micrograms ovalbumin/ml throughout the period of culture.


Pedometers and brief e-counseling: increasing physical activity for overweight adults.
Physical inactivity has emerged as a public health epidemic and is associated with the rising obesity rate. A multiple-treatments reversal design was utilized to test whether pedometer-aided self-monitoring and brief e-counseling could help 3 overweight adults increase their physical activity. Dependent measures were taken for pedometer steps and weight. Two participants approximately doubled their daily step totals and lost a modest amount of weight by study end.


Cloning and characterization of BS-cadherin, a novel cadherin from the colonial urochordate Botryllus schlosseri.
The genomic DNA for a novel member of the cadherin family (BS-cadherin) was cloned and characterized from the colonial marine invertebrate, Botryllus schlosseri. Using a differential display of mRNA by means of PCR, a small cDNA fragment of 380 nucleotides was found to be specifically expressed in a colony undergoing allogeneic rejection processes, as compared with naive parts of the same genotype. This cDNA fragment was used as a probe to screen a genomic library of Botryllus schlosseri. A genomic fragment containing an ORF of 2718 nucleotides, with no introns, was isolated. The encoded protein exhibits a typical structure of cadherins; an extracellular domain with conserved repeated sequences (cadherin signatures), a single transmembrane domain and a conserved cytoplasmic tail region. The BS-cadherin amino-acid sequence shows 32-35% identity to mature classical cadherins type I, e.g., N-, P- and E-cadherin as well as mature classical cadherins type II, e.g., human cadherin-6, -8 and OB-cadherin. This cadherin represents a new cadherin gene family, evolutionarily distant to all other known classical cadherins.


Bimetallic Pd/Sn-based Nanoparticles and their Catalytic Properties in the Semihydrogenation of Diphenylacetylene.
Multimetallic nanoparticles often enhance the catalytic performance of their monometallic counterparts by increasing reaction rates, catalyst selectivity, and/or stability. A prerequisite for understanding structure- and composition-associated properties, however, is the careful design of multimetallic nanoparticles with various structures and compositions. Here, bimetallic Pd/Sn-based nanoparticles are prepared with a tunable composition and structure exploiting ionic liquids (ILs) as reaction medium (i. e., methyltrioctylammonium bis(trifluoromethylsulfonyl)imide). The nanoparticles are obtained in a one-pot synthetic procedure by reducing the metal salt precursors with triethylborohydride in the IL. The results show that the reaction parameters, in particular the nature and ratio of the Pd2+ /Sn2+ precursors as well as the reaction temperature, influence NP formation and composition. X-ray diffraction with Rietveld analysis and transmission electron microscopy are employed to determine NP size and phase composition. Under optimized reaction conditions Pd2 Sn or PdSn nanocrystals are formed as single-phase products after introducing an additional annealing step at 200 °C. Nanocrystals with intermetallic composition reveal enhanced catalytic properties in the semihydrogenation of diphenylacetylene which was used as a model reaction.


An inhibitor(s) of globin mRNA translation in rabbit serum.
1. A factor found in rabbit serum inhibits globin mRNA translation in vitro. 2. Inhibition of globin mRNA translation has been demonstrated in a cell-free rabbit reticulocyte lysate. 3. The inactivation of globin mRNA translation is not attributed to either serum albumin or ribonuclease activities. 4. Dialyzing the inhibitor for 24 hr at 4 degrees C does not result in the diminution of the inhibiting activity. However, the activity of the inhibitor is destroyed by heating to 70-80 degrees C for 5 min or by treatment with trypsin for 2 hr. 5. Ion exchange chromatography points to the inhibitor being a neutral protein, whereas, polyacrylamide gel electrophoresis reveals one major band with mol. wt 43 kDa. 6. The activity of the inhibiting material 3-fold greater in anemic serum than in normal serum. 7. These studies suggest that rabbit serum contains a protein inhibitor that may play a physiological role in regulating protein synthesis in red cells.


The Winter Habitat Selection of Red Deer (Cervus elaphus) Based on a Multi-Scale Model.
Single-scale frameworks are often used to analyze the habitat selections of species. Research on habitat selection can be significantly improved using multi-scale models that enable greater in-depth analyses of the scale dependence between species and specific environmental factors. In this study, the winter habitat selection of red deer in the Gogostaihanwula Nature Reserve, Inner Mongolia, was studied using a multi-scale model. Each selected covariate was included in multi-scale models at their "characteristic scale", and we used an all subsets approach and model selection framework to assess habitat selection. The results showed that: (1) Univariate logistic regression analysis showed that the response scale of red deer to environmental factors was different among different covariate. The optimal scale of the single covariate was 800-3200 m, slope (SLP), altitude (ELE), and ratio of deciduous broad-leaved forests were 800 m in large scale, except that the farmland ratio was 200 m in fine scale. The optimal scale of road density and grassland ratio is both 1600 m, and the optimal scale of net forest production capacity is 3200 m; (2) distance to forest edges, distance to cement roads, distance to villages, altitude, distance to all road, and slope of the region were the most important factors affecting winter habitat selection. The outcomes of this study indicate that future studies on the effectiveness of habitat selections will benefit from multi-scale models. In addition to increasing interpretive and predictive capabilities, multi-scale habitat selection models enhance our understanding of how species respond to their environments and contribute to the formulation of effective conservation and management strategies for ungulata.


Long-term outcomes of preoperative docetaxel with cisplatin plus S-1 therapy for gastric cancer with extensive nodal metastasis (JCOG1002).
Preoperative chemotherapy with cisplatin plus S-1 (CS) followed by gastrectomy with D2 plus para-aortic lymph node (PAN) dissection is regarded as a standard treatment in Japan for advanced gastric cancer with bulky lymph node (BN) and/or PAN metastasis. In the JCOG1002, we added docetaxel to CS (DCS) to further improve long-term outcomes. However, the primary endpoint, clinical response rate (RR), did not reach the expected level (Ito et al. in Gastric Cancer 20:322-31, 2017). Herein, we report our long-term survival results. Patients with BN and/or PAN metastasis received 2 or 3 cycles of DCS therapy (docetaxel at 40 mg/m2 and cisplatin at 60 mg/m2 on day 1 and S-1 at 80 mg/m2 per day for 2 weeks, followed by a 2-week rest) followed by gastrectomy with D2 plus PAN dissection and postoperative S-1 for 1 year. Between July 2011 and May 2013, 53 patients were enrolled. Clinically, 17.0% had both PAN and BN metastasis, and the rest had either PAN (26.4%) or BN (56.6%) metastasis. Among all eligible patients, the 5-year overall survival was 54.9% (95% confidence interval 40.3-67.3%) at the last follow-up in May 2018. Among 44 eligible patients with R0 resection, the 5-year relapse-free survival was 47.7% (95% confidence interval 32.5-61.5%). Adding docetaxel to CS in preoperative chemotherapy for extensive nodal metastasis improved neither short-term outcomes nor long-term survival. Preoperative chemotherapy with CS followed by D2 + PAN dissection and postoperative S-1 remains the standard of care for patients with extensive nodal metastasis.


Production of enriched in B vitamins biomass of Yarrowia lipolytica grown in biofuel waste.
Yarrowia lipolytica as an oleaginous yeast is capable of growing in various non-conventional hydrophobic substrate types, especially industrial wastes. In this study, the content of thiamine (vitamin B1), riboflavin (vitamin B2), pyridoxine (vitamin B6), biotin (vitamin B7) and folic acid (vitamin B9) in the wet biomass of Y. lipolytica strains cultivated in biofuel waste (SK medium), compared to the standard laboratory YPD medium, was assessed. Additionally, the biomass of Y. lipolytica A-101 grown in biofuel waste (SK medium) was dried and examined for B vitamins concentration according to the recommended microbial methods by AOAC Official Methods. The mean values of these vitamins per 100 g of dry weight of Y. lipolytica grown in biofuel waste (SK medium) were as follows: thiamine 1.3 mg/100 g, riboflavin 5.3 mg/100 g, pyridoxine 4.9 mg/100 g, biotin 20.0 µg/100 g, and folic acid 249 µg/100 g. We have demonstrated that the dried biomass is a good source of B vitamins which can be used as nutraceuticals to supplement human diet, especially for people at risk of B vitamin deficiencies in developed countries. Moreover, the biodegradation of biofuel waste by Y. lipolytica is desired for environmental protection.


Central and regional hemodynamics determine optimal management of major venous injuries.
Controversy continues in the selection of optimal management of major venous injuries. We analyzed our experience with 191 major venous injuries in 163 patients (1986 to 1991). The mechanism of injury was gunshot (112), stab (44), blunt (six), and iatrogenic (one). Eighteen cervicothoracic, 51 caval, 30 iliac, 36 visceral, and 56 extremity veins were involved. Of the 191 injuries, 105 (54.9%) were repaired (lateral repair 76, end-to-end anastomosis 15, vein patch four, vein graft five, Gore-Tex graft four, and compilation one). Of the remaining venous injuries, 64 were ligated as a result of hemodynamic instability. Twenty-two injuries in 18 patients did not receive treatment because 16 of 18 patients died before vascular control or repair. The overall amputation rate was 1.2%, and the mortality rate was 28.2% (46/163). The highest mortality rate occurred in those patients who required resuscitative thoracotomy (100%, p < 0.00001), retrohepatic caval injuries (90%, p < 0.0004), and multiple venous injuries (81.8%, p < 0.00001). Seventeen patients underwent fasciotomies (15 prophylactic and two therapeutic). Clinical or measured venous hypertension by stump pressure assisted in deciding for venous repair in 20 patients. A significant decrease in venous stump pressure (p < 0.000001) was noted after venous reconstruction. Thus the decision to ligate or repair venous injuries correlated primarily with (1) hemodynamic stability, and in stable patients, with (2) extent and location of injury and (3) clinical and measured venous hypertension. Venous ligation in clinically stable patients did not increase the need for fasciotomy or amputation.(ABSTRACT TRUNCATED AT 250 WORDS)


A New Chemoenzymatic Semisynthetic Approach Provides Insight into the Role of Phosphorylation beyond Exon1 of Huntingtin and Reveals N-Terminal Fragment Length-Dependent Distinct Mechanisms of Aggregation.
Huntington's disease is a neurodegenerative disorder caused by the expansion of a polyglutamine repeat (>36Q) in the N-terminal domain of the huntingtin protein (Htt), which renders the protein or fragments thereof more prone to aggregate and form inclusions. Although several Htt N-terminal fragments of different lengths have been identified within Htt inclusions, most studies on the mechanisms, sequence, and structural determinants of Htt aggregation have focused on the Httexon1 (Httex1). Herein, we investigated the aggregation properties of mutant N-terminal Htt fragments of various lengths (Htt171, Htt140, and Htt104) in comparison to mutant Httex1 (mHttex1). We also present a new chemoenzymatic semisynthetic strategy that enables site-specific phosphorylation of Htt beyond Httex1. These advances yielded insights into how post-translational modifications (PTMs) and structured domains beyond Httex1 influence aggregation mechanisms, kinetics, and fibril morphology of longer N-terminal Htt fragments. We demonstrate that phosphorylation at T107 significantly slows the aggregation of mHtt171, whereas phosphorylation at T107 and S116 accelerates the aggregation, underscoring the importance of crosstalk between different PTMs. The mHtt171 proteins aggregate via a different mechanism and form oligomers and fibrillar aggregates with morphological properties that are distinct from that of mHttex1. These observations suggest that different N-terminal fragments could have distinct aggregation mechanisms and that a single polyQ-targeting antiaggregation strategy may not effectively inhibit the aggregation of all N-terminal Htt fragments. Finally, our results underscore the need for further studies to investigate the aggregation mechanisms of Htt fragments and how the various fragments interact with each other and influence Htt toxicity and disease progression.


Modeling coupled nanoparticle aggregation and transport in porous media: a Lagrangian approach.
Changes in nanoparticle size and shape due to particle-particle interactions (i.e., aggregation or agglomeration) may significantly alter particle mobility and retention in porous media. To date, however, few modeling studies have considered the coupling of transport and particle aggregation processes. The majority of particle transport models employ an Eulerian modeling framework and are, consequently, limited in the types of collisions and aggregate sizes that can be considered. In this work, a more general Lagrangian modeling framework is developed and implemented to explore coupled nanoparticle aggregation and transport processes. The model was verified through comparison of model simulations to published results of an experimental and Eulerian modeling study (Raychoudhury et al., 2012) of carboxymethyl cellulose (CMC)-modified nano-sized zero-valent iron particle (nZVI) transport and retention in water-saturated sand columns. A model sensitivity analysis reveals the influence of influent particle concentration (ca. 70 to 700 mg/L), primary particle size (10-100 nm) and pore water velocity (ca. 1-6 m/day) on particle-particle, and, consequently, particle-collector interactions. Model simulations demonstrate that, when environmental conditions promote particle-particle interactions, neglecting aggregation effects can lead to under- or over-estimation of nanoparticle mobility. Results also suggest that the extent to which higher order particle-particle collisions influence aggregation kinetics will increase with the fraction of primary particles. This work demonstrates the potential importance of time-dependent aggregation processes on nanoparticle mobility and provides a numerical model capable of capturing/describing these interactions in water-saturated porous media.


Immunotherapy of guinea pig line 10 hepatoma with nonliving BCG cells in aqueous medium.
Killed BCG cells suspended in 1.5% carboxymethylcellulose cured guinea pigs with established line 10 tumors in a high percentage of cases. The bacterial preparation of BCG in carboxymethylcellulose displayed a stronger tumor regressive activity and the process of healing was accelerated when endotoxin from a rough (Re) strain of Salmonella typhimurium was added to the BCG bacilli.


Commercial Air Travel for Passengers With Cardiovascular Disease: Recommendations for Common Conditions.
The exponential growth of commercial flights has resulted in an explosion of air travelers over the last few decades, including passengers with a wide range of cardiovascular conditions. Notwithstanding the ongoing COVID-19 pandemic that had set back the aviation industry for the next 1-2 years, air travel is expected to rebound fully by 2024. Guidelines and evidence-based recommendations for safe air travel in this group vary, and physicians often encounter situations where opinions and assessments on fitness for flights are sought. This article aims to provide an updated suite of recommendations for the aeromedical disposition of passenger with common cardiovascular conditions, such as ischemic heart disease, congestive heart failure, valvular heart disease, cardiomyopathies, and common arrhythmias.


Anatomy and surgery of the infected dermal sinus of the lower spine.
Cases of infected dermal sinus are scarce and detailed surgical anatomical descriptions are hardly found in literature. The clinical, radiological, and surgical findings in four cases of an infected dermal sinus located at the lower spine are presented to elucidate the pathological anatomical configuration. The first case showed two dermal sinuses with a parallel course extra- and intradurally, ending in a confluence of cavities connected to the conus. In this case, as well as in the fourth case, the signs and symptoms were those of meningitis. The second case presented with meningitis and a subdural empyema, while the third case presented with an intradermoid-intramedullary abscess at the junction between the DS and the conus. This child probably showed signs and symptoms of conus involvement as early as during pregnancy. The anatomy of the nervous elements in this congenital anomaly is heavily disturbed, more particularly in case of infection, due to extensive arachnoidal scarring. The latter renders dissection laborious and recognition of anatomical details difficult, resulting in complete excision of a dermal sinus in less than half of the cases. Despite their variability in presentation, most cases of an infected dermal sinus show similar characteristic features.


Comparison of Postoperative Port-Site Pain After Gallbladder Retrieval From Epigastric Versus Umbilical Port in Patients of Laparoscopic Cholecystectomy for Symptomatic Cholelithiasis: A Randomized Controlled Trial.
Introduction Gallbladder (GB) retrieval is an important cause of postoperative pain (POP) after laparoscopic cholecystectomy (LC). Retrieval is through the epigastric or umbilical port based on the surgeon's preference. There is limited evidence to support the superiority of one port over the other in terms of POP. This study was done to compare POP between epigastric and umbilical ports after GB retrieval in LC for symptomatic cholelithiasis. Material and methods All patients who underwent elective LC for symptomatic cholelithiasis were randomized for GB retrieval either through the umbilical (n = 15) or epigastric (n = 15) port. Postoperatively, the retrieval difficulty score by the operating surgeon, visual analog scale (VAS) scores for pain, and surgical site infection (SSI) by postoperative day (POD) 10 and 30 were assessed. Results The mean visual analog scores at the umbilical port at 1, 6, 12, 24, and 36 hours postoperatively were 5.20 ± 0.86, 4.60 ± 0.74, 4.00 ± 0.53, 3.40 ± 0.08, and 2.73 ± 0.82, which were significantly less than the visual analog scores at the epigastric port at the same time intervals, measuring 6.06 ± 1.34, 5.87 ± 1.30, 5.27 ± 1.16, 4.73 ± 1.10, and 3.93 ± 1.03, respectively. The difference was statistically significant between the two arms (p-value < 0.05). The mean retrieval difficulty score was significantly less for the umbilical port (4.40 ± 0.74) when compared with the epigastric port (5.13 ± 0.55). The overall SSI rate in the present study was 10%, and three (20%) patients in the epigastric port group developed SSI by POD 10, while none in the umbilical port group developed SSI. Conclusion GB retrieval from the umbilical port is associated with less POP, SSI, and retrieval difficulty when compared with GB retrieval from the epigastric port after elective LC for symptomatic cholelithiasis. Titration of analgesic use can also be done appropriately, reducing the dose of analgesics after 12-24 hours.


[Dice test--a simple method for assessment of visual acuity in infants with visual deficits].
Determination of visual acuity in low vision infants or patients with additional cerebral retardation is difficult. In our low vision department we used dice of different sizes and colors as well as other defined objects to determine visual acuity (VA). In this study we compared the results of the dice test with conventional tests for measurement of visual acuity. A total of 88 children with different causes of visual impairment e.g. albinism, retinal scars, retinopathy of prematurity (ROP), achromatopsia and optic atrophy etc., were included in this longitudinal study. Median follow-up time was 8.7 years (range 2.9-18.9 years). The first reliable examination was performed between the ages of 4 and 24 months (median 11 months). We estimated VA depending on the edge length of the dice, which were recognized at a distance of 30 cm, while 4 mm complied with VA 20/200. Best corrected binocular visual acuity was compared between the dice test, measurement with the Lea symbols and with numbers or Landolt rings. Estimation of visual acuity using the dice test was possible at the end of the first year of life (median 11 months, range 4-27 months). Although observation is limited to visual acuity results in the low vision range between light reaction and 20/120 there was nearly complete agreement between all three VA measurements. Visual acuity ranged from light perception to 20/20 with a median of 20/100. In 39 patients visual acuity was 20/200 or less at the end of the observation period. Visual acuity estimation overestimated visual acuity only in 5 out of the 88 patients, while in all of the patients with later acuity measurements better than 20/200, our best value of 20/200 was achieved. Using simple visual objects, such as dice with different colors and size down to an edge length of 4 mm, it is possible to estimate visual acuity in low vision infants within the first year of life. This option is also very helpful in patients who are not able to perform other visual acuity measurements or to give reliable answers using preferential looking, such as severely handicapped patients. In contrast to preferential looking with this dice test there is not only judgment of the reaction by the observer but also activity of the patient who grips the dice he can really see. This allows better counseling of families with low vision infants concerning current and later visual functions.


Interactive multiplanar reformation of conventional two-dimensional MR images.
In this report, we describe a new application for three-dimensional computer image processing that can provide for improved depiction of anatomical structures on routine nonvolumetric magnetic resonance (MR) examinations. The technique can be applied to standard two-dimensional MR images of the brain, spine, musculoskeletal system, and body including those obtained with relatively thick slices and with an intersection gap. This report demonstrates use of the reformation technique to establish retrospectively the symmetry in bilateral structures that were displayed out of alignment due to suboptimal patient positioning or patient motion during image acquisition and to improve the depiction of anatomical structures that were oriented out of the plane of original image acquisition. This method can be performed interactively in near real time, requires no increase in patient examination time, and has potential application throughout the body.


Quality of publications in emergency medicine.
The objective of this study is to describe emergency medicine (EM) publications in terms of methodology, approval by institutional review board, method of consent, external validity, and setting (eg, prehospital or emergency department). The 12 top-ranked emergency journals were selected. We manually reviewed the last 30 original articles in each EM journal, to represent more than 2 months of publications for all EM journals (range, 2-6 months). Only clinical original articles on human subjects were included. To ensure accurate data transcription, each article was read at least twice by 2 different reviewers and graded by written criteria using an extraction standard chart. Over the articles reviewed, 330 were analyzed. One hundred eighty-nine (57.3%) were prospective studies; 29 (8.8%) were randomized studies. Two hundred twenty-six studies (68.5%) mentioned an institutional review board approval or a waiver of authorization, and an informed consent was not mentioned in 227 (68.8%) of studies. Fifty-nine (17.9%) were conducted in a prehospital setting. Two hundred thirty-eight (72.1%) of these studies were at single-center institutions; the Unite States contributed 158 (47.9%) of the total publications. This study describes publications in the field of EM. Randomized studies represent 9% of publications, most studies are cross-sectional, and more than half have a retrospective design. We found that, in one-third of the studies, an institutional review board review was not mentioned and informed consent was not specified in two-thirds of the studies. Emergency medicine research volume, quality, and grants activity must increase in order for EM to progress within academic medicine.


Impact of Mobile Received Signal Strength (RSS) on Roaming and Non-roaming Mobile Subscribers.
Mobile phones have transitioned from voice-centric devices to smart devices supporting functionalities like high-definition video and games, web browsers, radio reception, and video conferencing. Mobile phones are used in telemedicine, health monitoring applications, navigation tools, and gaming devices, among other applications. Given the above, Mobile broadband connectivity affects mobile access to the internet and voice communications. This paper assesses the impact of the Reference Signal Received Power (RSRP) and broadband connectivity around Covenant University. LTE, GSM, and HSPA mobile signal measurement campaigns were conducted around Covenant University in Ota, Ogun state, Nigeria. To investigate the best optimized mobile network for mobile subscribers on roaming services and subscriber's high performance and data rates. After the experiment, exploratory data analysis was used to visualize the best mobile network; GSM proved as stable than LTE and HSPA.


Heterogeneity of Dyggve-Melchior-Clausen dwarfism.
Sibs with apparent Dyggve-Melchior-Clausen (DMC) dwarfism and normal intelligence are described. Three other familial and 3 sporadic cases with DMC dwarfism and normal intelligence are known. Twelve familial and 9 sporadic cases are known with the usual combination of DMC dwarfism and severe mental retardation. Since the two conditions appear to breed true they seem to be genetically different. We propose to name the former "Smith-McCort dwarfism" to clearly distinguish it from the DMC syndrome in which mental retardation is a constituent part. Both conditions are inherited as autosomal recessive traits. Spinal cord compression due to atlantoaxial instability is a serious and preventable complication of both disorders.


One hundred twin pairs patch tested with primary irritants.
The cutaneous sensitivity to benzalkonium chloride, sodium lauryl sulphate and potash soap was determined in 54 monozygotic and 46 dizygotic twin pairs. Comparing the intra-pair reaction strength a higher degree of concordance was found among monozygotic than among dizygotic twins, and even more so when monozygotic twins were compared with matched controls.


Central corneal thickness in a healthy Tunisian population.
To study the central corneal thickness of a Tunisian population and determine the influence of age, gender, axial length and refractive error on central corneal thickness (CCT) values. An observational, cross-sectional study was conducted on 608 eyes of consecutive Tunisian patients without ophthalmic disease. Corneal tomography (Oculus Pentacam, USA) and a complete eye examination were performed on all patients. The relationship between the central corneal thickness values and variables of age, refractive error, axial length and gender was assessed. The mean central corneal thickness was 522±37.17μm (range 461 to 655 μm). No statistical association was found between central corneal thickness values and variables of age, refractive error, axial length and gender. The normal CCT value in the Tunisian population was of 522±37.17 µm. We have analyzed, for the first time, normal central corneal thickness values of a healthy Tunisian population.


Toward an understanding of the distinctiveness of body-image constructs in persons categorized with overweight/obesity, bulimia nervosa, and binge-eating disorder.
We examined distinctiveness of different aspects of body-image disturbance in persons categorized with eating/weight disorders. We compared dissatisfaction with weight/shape, overvaluation of weight/shape, preoccupation with weight/shape, and fear of weight gain - in three study groups of persons categorized with overweight/obesity [O/O], bulimia nervosa [BN], and binge-eating disorder [BED] and examined how each body-image construct relates to clinical measures within and between the study groups. 1017 community volunteers completed measures of body-image, eating-disorder psychopathology, and depression. Participants were categorized into three study groups: O/O (N = 511), BN-purging type (N = 167), and BED (N = 339). Groups differed significantly on the four body-image constructs (medium-to-large effect sizes) with a consistent severity gradient with BN greater than BED greater than O/O. Both within and between groups, the four body-image constructs varied in strengths of association among themselves and with clinical measures. Analyses revealed considerable variability in variance accounted for in the clinical measures; distinctive significant patterns observed across the groups included: dissatisfaction with BMI, preoccupation and fear with eating concerns and restraint, and overvaluation with depression. Clinical manifestations of body-image disturbances are complex and show important differences across study groups defined as overweight/obesity, BN, and BED. Improved understanding of distinctions between different body-image constructs and their differential salience across different eating/weight disorders is needed to improve case conceptualization and treatment formulation.


Pathology of corneal hydrogel alloplastic implants.
Hydrogel keratophakia is a new form of lamellar refractive surgery which, in theory, can deal with almost all forms of refractive error. We examined the histopathological effects of several types of hydrogel materials on the cornea of non-human primates. With the exception of one type of hydrogel material, which was associated with endothelial cell degeneration, only minor histopathologic changes were seen up to a maximum of one year of observation, including thinning of the epithelium and decreased population of stromal keratocytes. These changes did not correlate with any clinical abnormalities. Additional extensive preclinical testing and eventual human clinical trials will determine the safety and efficacy of this procedure.


Insulin independence following isolated islet transplantation and single islet infusions.
To restore islet function in patients whose labile diabetes subjected them to frequent dangerous episodes of hypoglycemic unawareness, and to determine whether multiple transplants are always required to achieve insulin independence. The recent report by the Edmonton group documenting restoration of insulin independence by islet transplantation in seven consecutive patients with type 1 diabetes differed from previous worldwide experience of only sporadic success. In the Edmonton patients, the transplanted islet mass critical for success was approximately more than 9,000 IEq/kg of recipient body weight and required two or three separate transplants of islets isolated from two to four cadaveric donors. Whether the success of the Edmonton group can be recapitulated by others, and whether repeated transplants using multiple donors will be a universal requirement for success have not been reported. The authors report their treatment with islet transplantation of nine patients whose labile type 1 diabetes was characterized by frequent episodes of dangerous hypoglycemia. In each of the seven patients who have completed the treatment protocol (i.e., one or if necessary a second islet transplant), insulin independence has been achieved. In five of the seven patients only a single infusion of islets was required. To date, only one recipient has subsequently lost graft function, after an initially successful transplant. This patient suffered recurrent hyperglycemia 9 months after the transplant. This report confirms the efficacy of the Edmonton immunosuppressive regimen and indicates that insulin independence can often be achieved by a single transplant of sufficient islet mass.


Unveiling the nexus between parental exposure to toxicants and heritable spermiotoxicity - Is life history a shield or a shadow?
The knowledge on parental experiences is critical to predict how organisms react to environmental challenges. So, the DNA integrity of Procambarus clarkii spermatozoa exposed ex vivo to the herbicide penoxsulam (Px) or ethyl methanesulfonate (EMS; model genotoxicant) was assessed with and without the influence of in vivo parental exposure to the same agents. The parental exposure alone did not affect the DNA of unexposed spermatozoa. However, the history of Px exposure increased the vulnerability to oxidative lesions in Px-exposed offspring. Otherwise, parental exposure to EMS allowed the development of protection mechanisms expressed when F1 was also exposed to EMS, unveiling life history as a shield. The parental exposure to a different agent adverse and decisively affected Px spermiotoxic potential, pointing out life history as a shadow to progeny. Given the complexity of the aquatic contamination scenarios, involving mixtures, the spermiotoxicity of Px to wild P. clarkii populations emerged as probable.


Practical applicability of the STAMCO and ChOLE classification in cholesteatoma care.
To compare cholesteatoma care internationally and to evaluate outcomes, ear surgeons must use the same terminology. However, a clear universal definition on how to describe the extension, destruction and accompanying morbidity caused by the cholesteatoma is lacking. The practical applicability by means of interrater agreement is assessed for the STAMCO and the ChOLE classification. A total of 134 adult patients derived from the nationwide multicentre study in the Netherlands, entitled Dutch Cholesteatoma Data (DCD) were included. Retrospective analysis of 134 surgical reports according to the STAMCO and ChOLE classification for localisation/extension of the cholesteatoma, complication status and ossicular chain status. Both the percentage agreement and the interrater agreement were determined for each item of the classifications and interrater agreement was compared between the classifications as a whole. Differences in interrater agreement were found for both the localisation/extension of the cholesteatoma and ossicular chain status. STAMCO classification derived from the surgical report scored better on the localisation/extension of the cholesteatoma, whereas the ChOLE classification derived from the surgical report scored better on the status of the ossicular chain. In both classifications, complication status had a low agreement level but was also poorly registered in the surgical reports. Both STAMCO and ChOLE will be beneficial in uniform registration of cholesteatoma pathology in practice. Modifications proposed for both classifications may make them even more practical applicable in the future. A common denominator obtained from these two classifications may be incorporated in a standardised surgical report to facilitate evaluation which make outcomes transferable towards both classifications.


Pseudo-outbreak of Mycobacterium chimaera through aerators of hand-washing machines at a hematopoietic stem cell transplantation center.
We identified a waterborne pseudo-outbreak of Mycobacterium chimaera in our stem cell transplantation center, which likely resulted from biofilm on the aerators of the handwashing machines in each patient's room. Regular replacement of faucet parts can prevent biofilm formation and pseudo-outbreaks of M. chimaera through aerators.


Nuclear chromatin determination in amniotic fluid cells for prenatal sex prediction in the macaque.
Amniotic fluid cells obtained after the ninetieth day of gestation in the macaque were analyzed for nuclear chromatin. The technique proved reliable for the prediction of fetal sex.


Mannitol-specific enzyme II of the bacterial phosphotransferase system. II. Reconstitution of vectorial transphosphorylation in phospholipid vesicles.
Purified mannitol Enzyme II from Escherichia coli was reconstituted in phospholipid vesicles employing the octylglucoside dilution procedure and was shown to catalyze vectorial mannitol 1-phosphate:mannitol transphosphorylation. Reconstitution of the enzyme into liposomes showed a marked dependency upon the octylglucoside concentration with an optimum at 1.2%. The reconstituted transphosphorylation activity exhibited an absolute dependence upon mannitol 1-phosphate as the phosphoryl donor, was sensitive to N-ethylmaleimide, and had a pH optimum near 6. The intravesicular radiolabeled mannitol phosphate could be released from the proteoliposomes by the addition of either 50 microM unlabeled mannitol or 0.5% sodium dodecyl sulfate. The rate of formation of intraliposomal mannitol phosphate, measured as a function of the mannitol Enzyme II concentration, showed a sigmoidal response, suggesting that at high enzyme concentrations the mannitol Enzyme II exists in an aggregated or oligomeric state and that this form is more active than the monomeric or dissociated form of the enzyme in catalyzing the vectorial mannitol transphosphorylation reaction.


Metabolic Pathways as a Novel Landscape in Pancreatic Ductal Adenocarcinoma.
Metabolism plays a fundamental role in both human physiology and pathology, including pancreatic ductal adenocarcinoma (PDAC) and other tumors. Anabolic and catabolic processes do not only have energetic implications but are tightly associated with other cellular activities, such as DNA duplication, redox reactions, and cell homeostasis. PDAC displays a marked metabolic phenotype and the observed reduction in tumor growth induced by calorie restriction with in vivo models supports the crucial role of metabolism in this cancer type. The aggressiveness of PDAC might, therefore, be reduced by interventions on bioenergetic circuits. In this review, we describe the main metabolic mechanisms involved in PDAC growth and the biological features that may favor its onset and progression within an immunometabolic context. We also discuss the need to bridge the gap between basic research and clinical practice in order to offer alternative therapeutic approaches for PDAC patients in the more immediate future.


Significance of Antimicrobial Prophylaxis for the Prevention of Early-Onset Pneumonia After Radical Esophageal Cancer Resection: A Retrospective Analysis of 356 Patients Undergoing Thoracoscopic Esophagectomy.
Postoperative pneumonia is a common complication after esophagectomy and is associated with a high mortality rate. Although many randomized, controlled trials have been conducted on the prevention of postoperative pneumonia, little attention has been paid to the efficacy of antimicrobial prophylaxis. The purpose of this study was to investigate the impact of antimicrobial prophylaxis on the prevention of postoperative pneumonia. Data of patients with esophageal cancer who underwent thoracoscopic esophagectomy between 2016 and 2020 were collected. Early-period patients received cefazolin (CEZ) per protocol as antimicrobial prophylaxis (n = 250), and later-period patients received ampicillin/sulbactam (ABPC/SBT) (n = 106) because of the unavailability of CEZ in Japan. The incidence of pneumonia was compared between treatments in this quasi-experimental setting. Pneumonia detected by routine computed tomography (CT) on postoperative Days 5-6 was defined as early-onset pneumonia, and pneumonia that developed later was defined as late-onset pneumonia. The incidence of early-onset pneumonia was significantly lower (3.8% vs. 13.6%, P = 0.006), and the median length of postoperative hospital stay was significantly shorter (17 vs. 20 days, P < 0.001) in the ABPC/SBT group than in the CEZ group. The incidence of late-onset pneumonia was similar between groups (9.4% vs. 10.0%, P = 0.870). The incidence of Clostridioides difficile infections and the incidence of multidrug-resistant organisms were similar between groups. Multivariate analyses consistently showed the superiority of ABPC/SBT to CEZ in preventing early-onset pneumonia (odds ratio: 0.20, P = 0.006). ABPC/SBT after esophagectomy was better at preventing early-onset pneumonia compared with CEZ and was feasible regarding the development of antimicrobial resistance.


Thalamic connectivity of the second somatosensory area and neighboring somatosensory fields of the lateral sulcus of the macaque.
The thalamocortical relations of the somatic fields in and around the lateral sulcus of the macaque were studied following cortical injections of tritated amino acids and horseradish peroxidase (HRP). Special attention was paid to the second somatosensory area (S2), the connections of which were also studied by means of thalamic isotope injections and retrograde degeneration. S2 was shown to receive its major thalamic input from the ventroposterior inferior thalamic nucleus (VPI) and not, as previously reported, from the caudal division of the ventroposterior lateral nucleus (VPLc). Following small injections of isotope or HRP into the hand representation of S2, only VPI was labeled. Larger injections, which included the representations of more body parts, led to heavy label in VPI, with scattered label in VPLc, the central lateral nucleus (CL), and the posterior nucleus (Po). In addition, small isotope injections into VPLc did not result in label in S2 unless VPI was also involved in the injection site, and ablations of S2 led to cell loss in VPI. Comparison of injections involving different body parts in S2 suggested a somatotopic arrangement within VPI such that the trunk and lower limb representations are located posterolaterally and the hand and arm representations anteromedially. The location of the thalamic representations of the head, face, and intraoral structures that project to S2 may be in the ventroposterior medial nucleus (VPM). The granular (Ig) and dysgranular (Id) fields of the insula and the retroinsular field (Ri) each receive inputs from a variety of nuclei located at the posteroventral border of the thalamus. Ig receives its heaviest input from the suprageniculate-limitans complex (SG-Li), with additional inputs from Po, the magnocellular division of the medial geniculate n. (MGmc), VPI, and the medial pulvinar (Pulm). Id receives its heaviest input from the basal ventromedial n. (VMb), with additional inputs from VPI, Po, SG-Li, MGmc, and Pulm. Ri receives its heaviest input from Po, with additional input from SG-Li, MGmc, Pulm, and perhaps VPI. Area 7b receives its input from Pulm, the oral division of the pulvinar, the lateral posterior n., the medial dorsal n., and the caudal division of the ventrolateral n. These results indicate that the somatic cortical fields, except for those comprising the first somatosensory area, each receive inputs from an array of thalamic nuclei, rather than just one, and that individual thalamic somatosensory relay nuclei each project to more than one cortical field.


Successful treatment with daratumumab, lenalidomide, and dexamethasone therapy followed by autologous stem cell transplantation for newly diagnosed polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes syndrome: a case report.
Transplant-eligible patients with polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes syndrome are treated with induction therapy and autologous stem cell transplantation. Conventional induction therapies may exacerbate neuropathy and a high rate of disease progression within 5 years. Furthermore, only 50% of patients are able to walk independently after the therapies. Daratumumab, lenalidomide, and dexamethasone therapy has been reported as a less neurotoxic, highly effective therapy for patients with polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes syndrome who are ineligible for transplant or whose syndrome is relapsed/refractory, but no reports have provided data from untreated transplant-eligible patients. A 34-year-old Japanese woman displayed weakness, pain and edema in the lower limbs, decreased grip strength, amenorrhea, and abdominal distention. She was unable to walk independently. The patient was diagnosed with polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes syndrome and performed four courses of daratumumab, lenalidomide, and dexamethasone therapy, which enabled her to walk independently and did not exacerbate the neuropathy. Hematopoietic stem cells were collected using plerixafor and filgrastim in combination. Autologous stem cell transplantation was performed with high-dose melphalan. At 3-month post-transplantation follow-up, most of her clinical symptoms had disappeared. Daratumumab, lenalidomide, and dexamethasone therapy followed by autologous stem cell transplantation may be more effective than conventional therapy for newly diagnosed polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes syndrome. Although there was concerns that daratumumab, lenalidomide, and dexamethasone therapy might lead to poor mobilization of hematopoietic stem cells, this was overcome with the combination of plerixafor and filgrastim. The benefit of daratumumab, lenalidomide, and dexamethasone as induction therapy prior to autologous stem cell transplantation should be confirmed in future clinical trials.


Next-generation sequencing for diagnosis of infection: is more sensitive really better?
The utility of next-generation sequencing (NGS) in differentiating between active infection and contaminant or baseline flora remains unclear. The purpose of this study is to compare NGS with culture-based methods in primary shoulder arthroplasty. A prospective series of primary shoulder arthroplasty patients with no history of infection or antibiotic use within 60 days of surgery was enrolled. All patients received standard perioperative antibiotics. After skin incision, a 10 × 3-mm sample of the medial skin edge was excised. A 2 × 2-cm synovial tissue biopsy was taken from the rotator interval after subscapularis takedown. Each sample set was halved and sent for NGS and standard cultures. Samples from 25 patients were analyzed. Standard aerobic/anaerobic cultures were positive in 10 skin samples (40%, 95% confidence interval [CI] 20%-60%) and 3 deep tissue samples (12%, 90% CI 1%-23%]). NGS detected ≥1 bacterial species in 17 of the skin samples (68%, 95% CI 49%-87%) and 7 deep tissue samples (28%, 95% CI 9%-47%). There was a significant difference (P < .03) in the mean number of bacterial species detected with NGS between the positive standard culture (1.6 species) and the negative standard culture groups (5.7 species). NGS identified bacteria at higher rates in skin and deep tissue samples than standard culture did in native, uninfected patients undergoing primary procedures. Further research is needed to determine which NGS results are clinically relevant and which are false positives before NGS can be reliably used in orthopedic cases.


N,N'-Bis(2-chloro-phen-yl)succinamide.
There is one half-mol-ecule in the asymmetric unit of the title compound, C(16)H(14)Cl(2)N(2)O(2), with a center of symmetry at the mid-point of the central C-C bond. The N-H and C=O bonds in the C-NH-C(O)-C fragment are anti to each other and the amide O atom is anti to the H atoms attached to the adjacent C atoms. However, the conformation of the N-H bond in the amide fragments is syn to the ortho-chloro groups in the adjacent benzene rings. The dihedral angle between the benzene ring and the NH-C(O)-CH(2) fragment is 47.0 (2)°. In the crystal, a series of N-H⋯O inter-molecular hydrogen bonds link the mol-ecules into chains along the b axis.


Lower Limb Arterial Calcification and Acute Thrombosis Risk in Patients with Peripheral Artery Disease.
Calcification is closely related to in situ thrombosis secondary to plaque rupture in the coronary artery. However, the association between calcification in lower extremity arteries and acute thrombosis has not been assessed. We thus sought to determine whether lower limb arterial calcification (LLAC) was correlated with acute thrombosis in patients with symptomatic peripheral artery disease (PAD). We retrospectively reviewed consecutive patients presenting with symptomatic PAD between April 2017 and March 2018 who underwent lower extremity arterial evaluation by computed tomography (CT) angiography. Patient characteristics and cardiovascular risk factors were recorded, and LLAC scores were determined by noncontrast CT scans. Univariate and multivariate logistic regression was used to identify factors associated with acute thrombosis. The record search identified 201 patients with symptomatic PAD, including 24 with acute thrombosis and 177 without. Patients in the acute thrombosis group were significantly younger (P = 0.04) and had less diabetes mellitus (P = 0.04). Patients with acute thrombosis had more advanced ischemia at presentation (P < 0.01) and higher amputation rate within 30 days (P < 0.01). Univariate regression showed a significant association among acute thrombosis and age, diabetes mellitus, and LLAC score; in multivariable analysis, only the LLAC score (odds ratio 0.60, 95% confidence interval 0.37-0.98) maintained an association with acute thrombosis after adjusting for relevant risk factors. The LLAC score is independently and inversely associated with acute thrombosis in patients with PAD.


CTLA-4 and TNF-α promoter-308 A/G polymorphisms and ANCA-associated vasculitis susceptibility: a meta-analysis.
The aim of this study was to explore whether the cytotoxic T lymphocyte associated antigen-4 (CTLA-4) or tumor necrosis factor-α (TNF-α) polymorphisms contribute to anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) susceptibility. The authors conducted a meta-analysis on associations between polymorphisms of the 3' untranslated region (UTR) microsatellite at exon 3, exon 4 CT60 (A/G), exon 1 +49 (A/G), and promoter -318 (C/T) of CTLA-4, and TNF-α promoter-308 (A/G) and AAV susceptibility as determined using; (1) allelic contrast and (2) homozygote contrast, (3) recessive, and (4) dominant models. A total of 11 comparisons were considered in this meta-analysis. These studies encompassed 7 CTLA-4 studies and 4 TNF-α studies in 10 European populations and 1 Asian population. The (AT)n repeat polymorphisms of CTLA-4 were found to be significantly associated with AAV in European populations (OR of 86 vs. xx allele=0.402, 95% CI=0.184-0.875, P=0.022). The one study conducted on this polymorphism in Asians showed no significant association with AAV. Meta-analysis of the 86/86 (recessive effect), 86/86 and 86/xx (dominant effect), and 86/86 vs. xx/xx (homozygote contrast) of the (AT)n repeat revealed a significant association with AAV in Europeans. Both the CTLA-4 CT60 and +49 polymorphisms were found to be significantly associated with AAV in European populations, and allele and genotype-based analyses showed a significant association between the CTLA-4 CT60 and +49 polymorphisms with AAV in Europeans (OR of the A allele of CT60=0.769, 95% CI=0.619-0.017, P=0.035; OR of the T allele of +49=1.382, 95% CI=1.147-1.664, P=0.001, respectively). Meta-analysis of the CTLA-4 -318 polymorphism failed to identify any association with AAV. Furthermore, meta-analysis of the AA genotype, the AA and AG genotypes, and the A allele of TNF-α failed to reveal any association with Wegener's granulomatosis (WG). This meta-analysis demonstrates that the CTLA-4 polymorphisms confer susceptibility to AAV in Europeans. In contrast, no association was found between the TNF-α-308 polymorphism and susceptibility to WG in Europeans.


Bilobed flap reconstruction for skin defects after parotid carcinoma surgery.
To analyse the treatment results of bilobed flap reconstruction performed for skin defects after parotid carcinoma surgery. Ten patients who underwent bilobed flap reconstruction for skin defects after parotid carcinoma surgery in our hospital, from 2014 to 2020, were retrospectively enrolled. All patients underwent bilobed flap reconstruction for skin defects after parotid carcinoma surgery. The size of the skin defect was 2.7 × 2.2 cm in the smallest dimension and 9.0 × 6.3 cm in the largest dimension. All bilobed flaps except one healed without any problems. One patient developed partial flap necrosis in the retroauricular region, and was treated with skin grafts after removal of the necrotic tissue under local anaesthesia. All bilobed flaps, including the cases in which skin grafts were performed, survived after post-operative radiotherapy or chemotherapy. A bilobed flap is a good reconstruction option for skin defects after parotid carcinoma surgery in some cases.


Peritoneal clearances in scleroderma and diabetes mellitus: effects of intraperitioneal isoproterenol.
Reduced peritoneal clearances of creatinine and urate were demonstrated repeatedly in a patient with scleroderma and a patient with diabetes mellitus. Urea clearances were not significantly different from usual values. The findings suggest decreased peritoneal membrane permeability and/or area (if urea clearance is flow limited). Clearances increased to usual values with intraperitioneal isoproterenol in the patient with diabetes. There was no effect of isoproterenol in the patient with scleroderma.


Association between lead exposure from electronic waste recycling and child temperament alterations.
We aimed to evaluate the dose-dependent effects of lead exposure on temperament alterations in children from a primitive e-waste (obsolete electrical and electronic devices) recycling area in Guiyu of China and a control area (Chendian, China). Blood lead levels (BLL) might be correlated with temperament, health, and relevant factors that were evaluated through Parent Temperament Questionnaire (PTQ), physical examination, and residential questionnaires. We collected venipuncture blood samples from 303 children (aged 3-7 years old) between January and February 2008. Child BLL were higher in Guiyu than in Chendian (median 13.2 μg/dL, range 4.0-48.5 μg/dL vs. 8.2 μg/dL, 0-21.3 μg/dL) (P<0.01). Significant differences of mean scores in activity level (4.53±0.83 vs. 4.18±0.81), approach-withdrawal (4.62±0.85 vs. 4.31±0.89), and adaptability (4.96±0.73 vs. 4.67±0.83) were found between Guiyu and Chendian children (all P<0.01). High BLL (BLL≥10μg/dL) child had higher mean scores of approach-withdrawal when compared with those children with low BLL (BLL<10 μg/dL) (4.61±0.87 vs. 4.30±0.88, P<0.01). Location of child residence in Guiyu, and parents engagement in work related to e-waste were the risk factors related to child BLL, activity level, approach-withdrawal, adaptability, and mood. Child hand washing prior to food consumption was a protected factor for BLL and several dimensions. There are close relationships between BLL elevation, temperament alteration and the e-waste recycling activities in Guiyu. Primitive e-waste recycling may threaten the health of children by increasing BLL and altering children temperament, although the exposure to other toxicants needs to be examined in future studies.


BRG1 HSA domain interactions with BCL7 proteins are critical for remodeling and gene expression.
The SWI/SNF complex remodels chromatin in an ATP-dependent manner through the subunits BRG1 and BRM. Chromatin remodeling alters nucleosome structure to change gene expression; however, aberrant remodeling can result in cancer. We identified BCL7 proteins as critical SWI/SNF members that drive BRG1-dependent gene expression changes. BCL7s have been implicated in B-cell lymphoma, but characterization of their functional role within the SWI/SNF complex has been limited. This study implicates their function alongside BRG1 to drive large-scale changes in gene expression. Mechanistically, the BCL7 proteins bind to the HSA domain of BRG1 and require this domain for binding to chromatin. BRG1 proteins without the HSA domain fail to interact with the BCL7 proteins and have severely reduced chromatin remodeling activity. These results link the HSA domain and the formation of a functional SWI/SNF remodeling complex through the interaction with BCL7 proteins. These data highlight the importance of correct formation of the SWI/SNF complex to drive critical biological functions, as losses of individual accessory members or protein domains can cause loss of complex function.


Cooperative modular reinforcement learning for large discrete action space problem.
Deep reinforcement learning (DRL) has achieved remarkable results on high-dimension state tasks. However, it suffers in hard convergence and low sample efficiency when solving large discrete action space problems. To meet these challenges, we develop a cooperative modular reinforcement learning (CMRL) method to distributedly solve the problems with a large discrete action space. A general yet effective task decomposition method is proposed to decompose the complex decision task in a large action space into multiple decision sub-tasks in small action subsets, using a rule-based action division method. The CMRL method consisting of multiple Critic networks is proposed to settle the multiple sub-tasks, where each Critic network learns a decomposed value function to obtain the local optimal action in a sub-task. The global optimal action is cooperatively chosen by all local optimal actions. Moreover, we propose a new parallel training mechanism, which trains multiple Critic networks with different models and multi-data in parallel. Mathematical properties are proposed to analyze the rationality and superiority of CMRL. Four different simulation experiments are conducted to verify the generality and effectiveness of CMRL for large action space problems. The results show that CMRL has superior performance on training efficiency compared with classical and latest DRL methods while maintaining the accuracy of the solution.


Comparative genomics of Klebsiella michiganensis BD177 and related members of Klebsiella sp. reveal the symbiotic relationship with Bactrocera dorsalis.
Bactrocera dorsalis is a destructive polyphagous and highly invasive insect pest of tropical and subtropical species of fruit and vegetable crops. The sterile insect technique (SIT) has been used for decades to control insect pests of agricultural, veterinary, and human health importance. Irradiation of pupae in SIT can reduce the ecological fitness of the sterile insects. Our previous study has shown that a gut bacterial strain BD177 that could restore ecological fitness by promoting host food intake and metabolic activities. Using long-read sequence technologies, we assembled the complete genome of K. michiganensis BD177 strain. The complete genome of K. michiganensis BD177 comprises one circular chromosome and four plasmids with a GC content of 55.03%. The pan-genome analysis was performed on 119 genomes (strain BD177 genome and 118 out of 128 published Klebsiella sp. genomes since ten were discarded). The pan-genome includes a total of 49305 gene clusters, a small number of 858 core genes, and a high number of accessory (10566) genes. Pan-genome and average nucleotide identity (ANI) analysis showed that BD177 is more similar to the type strain K. michiganensis DSM2544, while away from the type strain K. oxytoca ATCC13182. Comparative genome analysis with 21 K. oxytoca and 12 K. michiganensis strains, identified 213 unique genes, several of them related to amino acid metabolism, metabolism of cofactors and vitamins, and xenobiotics biodegradation and metabolism in BD177 genome. Phylogenomics analysis reclassified strain BD177 as a member of the species K. michiganensis. Comparative genome analysis suggested that K. michiganensis BD177 has the strain-specific ability to provide three essential amino acids (phenylalanine, tryptophan and methionine) and two vitamins B (folate and riboflavin) to B. dorsalis. The clear classification status of BD177 strain and identification of unique genetic characteristics may contribute to expanding our understanding of the symbiotic relationship of gut microbiota and B. dorsalis.


Does the addition of motor control or strengthening exercises to education result in better outcomes for rotator cuff-related shoulder pain? A multiarm randomised controlled trial.
To compare the short-term, mid-term and long-term effects between three interventions (education only, education and strengthening exercises, education and motor control exercises) for rotator cuff-related shoulder pain (RCRSP) on symptoms and function. 123 adults presenting with RCRSP took part in a 12-week intervention. They were randomly assigned to 1 of 3 intervention groups. Symptoms and function were evaluated at baseline and at 3 weeks, 6 weeks, 12 weeks and 24 weeks using the Disability of Arm, Shoulder and Hand Questionnaire (QuickDASH) (primary outcome) and Western Ontario Rotator Cuff Index (WORC). Linear mixed modelling was used to compare the effects of the three programmes on the outcomes. After 24 weeks, between-group differences were -2.1 (-7.7 to 3.5) (motor control vs education), 1.2 (-4.9 to 7.4) (strengthening vs education) and -3.3 (-9.5 to 2.8) (motor control vs strengthening) for the QuickDASH and 9.3 (1.5 to 17.1) (motor control vs education), 1.3 (-7.6 to 10.2) (strengthening vs education) and 8.0 (-0.5 to 16.5) (motor control vs strengthening) for the WORC. There was a significant group-by-time interaction (p=0.04) with QuickDASH, but follow-up analyses did not reveal any clinically meaningful between-group differences. There was no significant group-by-time interaction (p=0.39) for the WORC. Between-group differences never exceeded the minimal clinically important difference of QuickDASH or WORC. In people with RCRSP, the addition of motor control or strengthening exercises to education did not lead to larger improvements in symptoms and function compared with education alone. Further research should investigate the value of providing stepped care by identifying individuals who may only need education and those who would benefit from the addition of motor control or strengthening exercises. NCT03892603.


Prevalence and predictors of teenage pregnancy in Pakistan: a trend analysis from Pakistan Demographic and Health Survey datasets from 1990 to 2018.
Teenage pregnancies carry an increased risk of adverse obstetric and health outcomes for mothers and children. This study assessed the prevalence and predictors of teenage pregnancies over time in Pakistan using the Pakistan Demographic and Health Survey (PDHS). Data on 400 076 ever-married pregnant women aged 15-49 y from four PDHS datasets were used. Teenage pregnancy was the outcome variable, whereas a woman's and her partner's education, occupation, wealth quintile, region, place of residence and access to knowledge on family planning were the explanatory variables. Pooled prevalence was estimated and regression analysis was undertaken to produce an adjusted prevalence ratio with 95% CIs. Although the prevalence of teenage pregnancy decreased from 54.4% in 1990-1991 to 43.7% in 2017-2018, the pooled prevalence was 42.5% (95% CI 37.9 to 49.6%). The prevalence of teenage pregnancy was significantly associated with place of residence, wealth quintile, education and occupation. Despite a growing focus on women's education, access to sexual and reproductive health (SRH) services and contraception in the last decade in Pakistan, the prevalence of teenage pregnancy is still high. There is a pressing need to develop appropriate strategies for increasing access to education, SRH services and use of contraception in Pakistan.


HPLC method for determination of diclofenac in human plasma and its application to a pharmacokinetic study in Turkey.
A simple high-performance liquid chromatography (HPLC) method has been developed for determination of diclofenac in human plasma. The method was validated on Ace C(18) column using UV detection. The mobile phase consisted of 20 mM phosphate buffer (pH 7) containing 0.1% trifluoroacetic acid-acetonitrile (65:35, v/v). Calibration curve was linear between the concentration range of 75-4000 ng/mL. Intra- and inter-day precision values for diclofenac in plasma were less than 3.6, and accuracy (relative error) was better than 5.3%. The limits of detection and quantification of diclofenac were 25 and 75 ng/mL, respectively. Also, this assay was applied to determine the pharmacokinetic parameters of diclofenac in healthy Turkish volunteers who had been given 50 mg diclofenac.


Molecular characterization of the lincomycin-production gene cluster of Streptomyces lincolnensis 78-11.
The lincomycin (LM)-production gene cluster of the overproducing strain Streptomyces lincolnensis 78-11 was cloned, analysed by hybridization, as well as by DNA sequencing, and compared with the respective genome segments of other lincomycin producers. The lmb/lmr gene cluster is composed of 27 open reading frames with putative biosynthetic or regulatory functions (lmb genes) and three resistance (lmr) genes, two of which, lmrA and lmrC, flank the cluster. A very similar overall organization of the lmb/lmr cluster seems to be conserved in four other LM producers, although the clusters are embedded in non-homologous genomic surroundings. In the wild-type strain (S. lincolnensis NRRL2936), the lmb/lmr-cluster apparently is present only in single copy. However, in the industrial strain S. lincolnensis 78-11 the non-adjacent gene clusters for the production of LM and melanin (melC) both are duplicated on a large (0.45-0.5 Mb) fragment, accompanied by deletion events. This indicates that enhanced gene dosage is one of the factors for the overproduction of LM and demonstrates that large-scale genome rearrangements can be a result of classical strain improvement by mutagenesis. Only a minority of the putative Lmb proteins belong to known protein families. These include members of the gamma-glutamyl transferases (LmbA), amino acid acylases (LmbC), aromatic amino acid aminotransferases (LmbF), imidazoleglycerolphosphate dehydratases (LmbK), dTDP-glucose synthases (LmbO), dTDP-glucose 4,6-dehydratases (LmbM) and (NDP-) ketohexose (or ketocyclitol) aminotransferases (LmbS). In contrast to earlier proposals on the biosynthetic pathway of the C-8 sugar moiety (methylthiolincosaminide), this branch of the LM pathway actually seems to be based on nucleotide-activated sugars as precursors.


How a Large Academic Training Program Influences Early Career Decision-making and Employment Stability in Urology.
To characterize training and practice factors that influence early career stability and satisfaction in urology residency and fellowship graduates. A computer-based survey was distributed to residency and fellowship graduates from a single, large US training program from 1992 to 2015. Queries encompassed training program specifics, post-training practice characteristics, and a validated burnout assessment. Of 108 surveyed individuals there were 77 (71.3%) respondents. Fifty-one (67.1%) remained in their first position after residency. While 52 (67.5%) urologists reported that the program did not formally assist in finding their first post-residency position, no respondent reported difficulty securing a position. Proximity to family was a major factor in selecting a post-residency position in 40 (51.9%) of respondents. Twenty-nine (37.7%) participants joined practices with at least one other graduate of the same urology training program on staff and 24 remain in this position (82%). Urology graduates from a large US training program did not have difficulty finding employment after training and most remain in their first post-training position. While proximity to family was a strong consideration for graduates, the perceived importance of first-position characteristics varied widely. 37.7% of our cohort took initial positions at a practice already employing a graduate from the same training program with >80% staying in this position. Surveying a broader range of programs may help future graduates and training programs better tailor their mentorship curricula and alumni networks to trainee goals.


Light activated calcium release in Limulus ventral photoreceptors as revealed by laser confocal microscopy.
Using confocal imaging and fluorescent calcium indicators, light-induced elevation of intracellular Ca2+ concentration ([Ca2+]i) in Limulus ventral photoreceptors was shown to be initiated within 4 microns of the light-sensitive plasma membrane. Within 500 ms, elevation of [Ca2+]i spread throughout the light-sensitive rhabdomeral lobe of the photoreceptor, but barely penetrated the arhabdomeral lobe. During saturating illumination of measurement spots near the plasma membrane, [Ca2+]i rose at rates of 1-2 mM/s after a latent period of 14-40 ms, reaching peak concentrations of approximately 150 microM. Rapid elevation of [Ca2+]i persisted in the absence of extracellular Ca2+ and was therefore ascribed to release from intracellular stores. The elevation of [Ca2+]i was always detectable within 5 ms of the electrical response of the photoreceptor to light. In 14 out of 54 measurements, detection of elevated calcium preceded the electrical response. Cyclopiazonic acid, an inhibitor of endoplasmic reticulum Ca-pumps, greatly reduced the elevation of [Ca2+]i during bright flashes and the sensitivity of the electrical response to dim flashes. However, the maximal response to bright flashes was not diminished. Therefore, although the calcium release that we detect may be fast enough to contribute to the electrical response we are unable to demonstrate that it is absolutely required.


Are econazole, miconazole and clotrimazole mutagenic to bacteria?
The fungistatic drugs econazole, miconazole and clotrimazole were investigated as to mutagenic properties in the fluctuation test with Klebsiella pneumoniae and Escherichia coli K12 as test organisms and in the plate-incorporation test, with and without metabolic activation, with Salmonella typhimurium strains TA98 and TA100. No mutagenic activity of the 3 compounds on these microorganisms was found.