Risk of subsequent malignant neoplasms among 1,641 Hodgkin's disease patients diagnosed in childhood and adolescence: a population-based cohort study in the five Nordic countries. Association of the Nordic Cancer Registries and the Nordic Society of Pediatric Hematology and Oncology.
To assess the risk of subsequent malignant neoplasms among Hodgkin's disease patients diagnosed before 20 years of age in the five Nordic countries (Denmark, Finland, Iceland, Norway, and Sweden). There were 1,641 Hodgkin's disease patients identified through the national cancer registries since the 1940s or 1950s. The patients were monitored for 17,000 person-years until the end of 1991. Expected figures were derived from the age-specific incidence rates in each country and standardized incidence ratios (SIR) were calculated. A total of 62 subsequent neoplasms were diagnosed (SIR, 7.7; 95% confidence interval [CI], 5.9 to 9.9). The overall cumulative risk of subsequent neoplasms was 1.9% at the 10-year follow-up point, 6.9% at 20 years, and 18% at 30 years. There were 26 subsequent neoplasms among males (SIR, 6.5; 95% CI, 4.3 to 9.6) and 36 among females (SIR, 8.9; 95% CI, 6.2 to 12), of which 16 were breast cancers (SIR, 17; 95% CI, 9.9 to 28). High risks were seen for thyroid cancer (SIR, 33; 95% CI, 15 to 62), for secondary leukemia (SIR, 17; 95% CI, 6.9 to 35), and for non-Hodgkin's lymphoma (SIR, 15; 95% CI, 4.9 to 35). The relative risk increased from 3.3 (95% CI, 1.2 to 7.1) for Hodgkin's disease patients diagnosed in the 1940s and 1950s to 15 (95% CI, 7.4 to 27) in the 1980s. The highest risk of secondary leukemia (SIR, 68; 95% CI, 18 to 174) was seen among those diagnosed with Hodgkin's disease in the 1980s. Patients who survive Hodgkin's disease at a young age are at very high relative risk of subsequent malignant neoplasms throughout their lives. In particular, the high relative risk of breast cancer following Hodgkin's disease in the teenage years calls for enhanced activity for early diagnosis.


[Spontaneous hepatic rupture of pregnancy. A report of four cases and medical literature review].
The spontaneous liver rupture associated with preeclampsia is a potential life threatening condition that requires a multidisciplinary team approach. There are near 200 cases reported in the world literature. This paper presents four cases of liver rupture associated with preeclampsia, three of which were consecutive with only two days apart, describing the clinical features and the therapeutic approaches. We also discussed about the mortality, which occurred in one of our cases, and perinatal mortality that affected one newborn and another one had neonatal encephalopathy secuelae. Three of the cases were managed in a surgical manner, one of them also with selective hepatic artery embolization meanwhile another one received conservative management. It is important to suspect this pathology in the preeclamptic patient, especially if she develops HELLP syndrome, in order to establish opportune diagnosis and treatment with a team including the intensive care, surgery and obstetrical staff.


Cytoskeletal and contractile proteins in detrusor smooth muscle from bladders with outlet obstruction--a comparative study in rat and man.
Detrusor biopsies were obtained from patients with urinary outlet obstruction due to prostatic enlargement and from age-matched control patients. The relative amounts of actin and myosin and their isoforms, as well as desmin and filamin were determined and compared with corresponding results from bladders from control rats and rats with 10 days of experimental outlet obstruction of the urinary bladder. In the human control detrusor the actin/myosin ratio was similar to that in the control rat. The isoform distribution of the myosin heavy chains differed between man and rat. In the biopsies from the patients with outlet obstruction and in the obstructed rat bladders the actin/myosin ratio was increased. A change in the myosin heavy chain distribution in the obstructed bladders was observed for both species. The filamin/actin ratio increased significantly in the obstructed rat bladders and tended to increase in the obstructed human bladders. Desmin was the dominating intermediate filament protein. The desmin/actin ratio increased in obstructed bladders in man and in rat.


What is the optimal regimen for vitamin D?
The past 30 years have seen substantial advances in our understanding of the pathogenesis of the mineral, hormonal and skeletal disorders that comprise renal osteodystrophy. The introduction of calcitriol and alfacalcidol as treatments for this disorder in the early 1970s represented an enormous step forward in clinical practice, but unfortunately, the subsequent refinement of these therapies still leaves us well short of the ideal: hyperphosphatemia and hypercalcemia induced by the vitamin D metabolites, and failure to control parathyroid hyperplasia, all remain problematic. Novel pulsed regimens using alfacalcidol and calcitriol, while clearly effective, have not fulfilled initial high expectations of superiority in the context of comparative studies. New vitamin D metabolites, some of which have exhibited desirable selectivity in experimental settings with reduced tendency to raise phosphate and/or calcium while maintaining good control of the parathyroid glands, are now being evaluated. Of these, 22-oxacalcitriol, paricalcitol (19 nor-1,25 dihydroxyvitamin D2) and doxercalciferol (1 alpha-hydroxyvitamin D2) have all shown high efficacy when compared with placebo, but so also did alfacalcidol and calcitriol in similar studies in the 1970s and 1980s. The results of randomized studies comparing the new vitamin D metabolites with current standard therapy (alfacalcidol or calcitriol) are either not yet available or show uncertain benefits in relation to hypercalcemia, hyperphosphatemia and hyperparathyroidism. The impact of these new metabolites on the increasing prevalence of low turnover bone disease is unknown, although experimentally there is evidence of potentially important differences at the level of the skeleton.


Biliary inter-relationship between phospholipid, bilirubin and taurocholate in the anaesthetized rat.
The interference between biliary phospholipid and bilirubin secretion was investigated in rats with bile fistulae, under conditions of normal and maximal bilirubin secretion. The enterohepatic circulation of bile salts was interrupted and the animals received infusions of sodium taurocholate, a micelle-forming physiological bile salt. Sodium taurocholate infusion (0.19 mumol min-1 100 g-1 body weight) induced an increase in bile flow and phospholipid secretion, while basal bilirubin secretion was not increased. Bilirubin infusion (0.26 mumol min-1 100 g-1 body weight) induced a decrease in basal and taurocholate-stimulated phospholipid secretion. Biliary mixed micelle formation was presumably altered during bilirubin infusion, although bile taurocholate concentration, taurocholate secretion rate and bile flow were not modified. When sodium taurocholate was infused during bilirubin-decreased phospholipid secretion, this secretion was restored but maximal biliary bilirubin secretion was not increased. These results provide circumstantial evidence for the hypothesis that mixed micelle formation is not an important determinant of maximal bilirubin transport into bile.


Octreotide reduces alcohol-induced hypotension and orthostatic symptoms in primary autonomic failure.
Symptomatic postural hypotension is a major problem in patients with primary idiopathic autonomic failure, and ingestion of small quantities of alcohol may worsen the degree of postural hypotension. The proposed mechanisms include mesenteric vasodilation and release of vasodilatory gut peptides. We measured systemic, mesenteric, other regional vascular and biochemical responses to alcohol ingestion before and after pre-treatment with the somatostatin analogue Octreotide (which inhibits the release of a wide range of gut peptides normally released in response to food ingestion) in six patients with primary autonomic failure. Octreotide effectively prevented alcohol-induced hypotension and vasodilatation of the mesenteric vascular bed, with improvement of signs and symptoms of hypotension post-alcohol. This suggests that the mechanism of alcohol-induced symptomatic hypotension in autonomic failure is at least partly mediated by release of vasodilatatory gut peptides with resultant mesenteric vasodilatation.


Resilient children: individual differences in developmental outcome of children born to drug abusers.
Since 1977, we have been following the neurobehavioral development of two groups of children: a group born to women on methadone maintenance and a drug-free comparison group. This study used the data on the children evaluated at 36 months of age to determine whether distinct patterns of developmental outcome can be identified, and which medical, familial, or environmental characteristics are associated with developmental differences. The children were clustered on four measures at 36 months: head circumference percentile, Merrill-Palmer Scale score, neurological evaluation, and referrals for developmental problems. Three distinct clusters emerged, with methadone children disproportionately frequent in Cluster 3, the group showing the poorest development. Comparisons of the clusters on a wide range of variables revealed consistent differences between Cluster 1 and Cluster 3 children in maternal responsiveness and incidence of neglect and family violence. These findings indicate that distinct developmental patterns do occur within this predominantly lower-class ghetto population; further, that children born to methadone-maintained women are more likely to show poor development. However, when the environment provides nurturance and stability, methadone children can show resilience and develop well.


Role of the trace amine associated receptor 5 (TAAR5) in the sensorimotor functions.
Classical monoamines are well-known modulators of sensorimotor neural networks. However, the role of trace amines and their receptors in sensorimotor function remains unexplored. Using trace amine-associated receptor 5 knockout (TAAR5-KO) mice, that express beta-galactosidase mapping its localization, we observed TAAR5 expression in the Purkinje cells of the cerebellum and the medial vestibular nucleus, suggesting that TAAR5 might be involved in the vestibular and motor control. Accordingly, in various behavioral tests, TAAR5-KO mice demonstrated lower endurance, but better coordination and balance compared to wild-type controls. Furthermore, we found specific changes in striatal local field potentials and motor cortex electrocorticogram, such as a decrease in delta and an increase in theta oscillations of power spectra, respectively. The obtained data indicate that TAAR5 plays a considerable role in regulation postural stability, muscle force, balance, and motor coordination during active movements, likely via modulation of monoaminergic systems at different levels of sensorimotor control involving critical brain areas such as the brainstem, cerebellum, and forebrain.


Further steps in TANGO: improved taxonomic assignment in metagenomics.
TANGO is one of the most accurate tools for the taxonomic assignment of sequence reads. However, because of the differences in the taxonomy structures, performing a taxonomic assignment on different reference taxonomies will produce divergent results. We have improved the TANGO pipeline to be able to perform the taxonomic assignment of a metagenomic sample using alternative reference taxonomies, coming from different sources. We highlight the novel pre-processing step, necessary to accomplish this task, and describe the improvements in the assignment process. We present the new TANGO pipeline in details, and, finally, we show its performance on four real metagenomic datasets and also on synthetic datasets. The new version of TANGO, including implementation improvements and novel developments to perform the assignment on different reference taxonomies, is freely available at http://sourceforge.net/projects/taxoassignment/.


Role of taurine in the central nervous system.
Taurine demonstrates multiple cellular functions including a central role as a neurotransmitter, as a trophic factor in CNS development, in maintaining the structural integrity of the membrane, in regulating calcium transport and homeostasis, as an osmolyte, as a neuromodulator and as a neuroprotectant. The neurotransmitter properties of taurine are illustrated by its ability to elicit neuronal hyperpolarization, the presence of specific taurine synthesizing enzyme and receptors in the CNS and the presence of a taurine transporter system. Taurine exerts its neuroprotective functions against the glutamate induced excitotoxicity by reducing the glutamate-induced increase of intracellular calcium level, by shifting the ratio of Bcl-2 and Bad ratio in favor of cell survival and by reducing the ER stress. The presence of metabotropic taurine receptors which are negatively coupled to phospholipase C (PLC) signaling pathway through inhibitory G proteins is proposed, and the evidence supporting this notion is also presented.


The relationship between linguistic and non-linguistic cognitive control skills in bilingual children from low socio-economic backgrounds.
The present study examined whether linguistic cognitive control skills were related to non-linguistic cognitive control skills in monolingual children (Study 1) and in bilingual children from low socio-economic status (SES) backgrounds (Study 2). Linguistic inhibitory control was measured using a grammaticality judgment (GJ) task in which children judged the grammaticality of sentences while ignoring their meaning. Non-linguistic inhibitory control was measured using a flanker task. Study 1, in which we tested monolingual English-speaking children, revealed that better inhibitory control skills, as indexed by the performance on the flanker task, were associated with improved performance on the GJ task. Study 2, in which we tested bilingual English-Spanish speaking children from low SES backgrounds, revealed that better non-linguistic inhibitory control skills did not yield better performance on the GJ task. Together, these findings point to a role of domain-general attention mechanisms in language performance in typically developing monolingual children, but not in bilingual children from low SES. Present results suggest that the relationship between linguistic and domain-general cognitive-control abilities is instantiated differently in bilingual vs. monolingual children, and that language-EF interactions are sensitive to language status and SES.


Comparing the concepts of mental load and stress.
This paper delineates mental load and stress as two related concepts that originate from different theoretical frameworks. A proper distinction between the two concepts is important, not only for theory building, but because it may lead also to different interpretations of experimental results, and, consequently, to different recommendations in applied situations. High workload is regarded as an important but not a critical factor in the development of stress symptoms. It is quite possible to work hard in difficult and complex tasks, even under unfavourable conditions, without cognitive strain, psychosomatic complaints, or adverse physiological effects. High task demands can be met by mobilizing extra energy through mental effort. This 'trying harder' reaction is a normal and healthy coping strategy to adapt to situational demands. In contrast, stress is regarded as a state in which the equilibrium between cognitive and energetical processes is disturbed by ineffective energy mobilization and negative emotions. Stress typically is characterized by inefficient behaviour, overreactivity, and the incapacity to recover from work. Stress is regarded as a state in which the physiological system is disorganized, which results in decreased well-being, sleeping problems, psychosomatic complaints, and increased health risks.


Valuing different human lives.
Do people think of the value of all human lives as equivalent irrespective of age? Affirmations of the equal value of all human lives are culturally prominent, yet much evidence points to the fact that the young are often prioritized over the old in life-and-death decision-making contexts. Studies 1-3 aimed to reconcile this tension by showing that although individuals are seen as more equal with respect to negative rights not to be harmed or killed (though not completely equal), they are seen as less equal with respect to positive rights to be aided or saved. Age exerts a large and systematic impact on decisions about who to save and about whose death is more tragic, suggesting that individuals are seen as possessing differing amounts of contingent value. These initial studies also yielded the novel finding that, although children are prioritized over adults, older children are often prioritized over younger children. Study 4 replicated this finding with a think-aloud methodology; the study showed that the preference for older children appears to be driven by their having had more invested in their lives, their better developed social relations, and their greater understanding of death. Studies 5a-5c demonstrated the independent causal effects of each of these variables on judgments of life's value. Finally, in Studies 6 and 7, mediation methods were used to show that older children's more meaningful social relations primarily explain the greater value of older than of younger children. These findings have implications for bioethics and medical policy.


Visual detection of multi-letter patterns.
This study addressed two basic questions about the detection of multi-letter patterns: (a) How is the detection of a multi-letter pattern related to the detection of its individual components? (b) How is the detection of a sequence of letters influenced by the observer's familiarity with that sequence? In three experiments observers searched for one-, two-, or three letter patterns embedded in a rapid series of multiple six-letter frames. In Experiment 1, unfamiliar two-letter patterns were detected more accurately than their one-letter components. This two-letter advantage reflects the fact that in an array of fixed size, larger target stimuli contain more information and are easier to discriminate from nontarget alternatives. Quantitative analyses indicated that observers combine information not decisions, about the component letters in a pattern. In Experiment 2, with statistical and physical properties equated, a familiar three-letter pattern (i.e., CAT) was detected more accurately than its unfamiliar anagram (i.e., TCA). This word advantage in word (not letter) detection persisted even after extensive practice and was uninfluenced by the lexical character of distractor items. In Experiment 3, words (e.g., FIB), pronounceable non words (e.g., FIF(, and familiar acronyms (e.g., FBI) were detected more readily than unfamiliar items (e.g., IBF). Thus both orthographic knowledge and familiarity with specific sequences can facilitate perceptual processing in "word" detection.


Inhibitory action of certain cyclophosphate derivatives of cAMP on cAMP-dependent protein kinases.
A series cAMP derivatives with modifications in the adenine, ribose and cyclophosphate moiety were screened for their binding affinity for the two types of cAMP-binding sites in mammalian protein kinase type 1. In addition, the activation of the kinase by these analogs was monitored. The binding data indicate that cAMP is bound to both sites in a comparable manner: the adenine appears to have no hydrogen-bond interactions with the binding sites, whereas the ribose may be bound by three hydrogen bonds involving the 2', 3' and 5' positions of cAMP. The binding data are not conclusive about the nature of the interaction with the exocyclic oxygen atoms on phosphorus, though a charge interaction seems to be absent. The cAMP molecule seems to be bound in the syn conformation. The results of activation experiments show that modifications in the adenine and ribose moiety do not affect the maximal activation level, while alteration of the two exocyclic oxygen atoms may result in a reduced maximal activation level and in one case, (Rp)-adenosine 3', 5'-monophosphorothioate [Rp-cAMPS], in total absence of activation even at concentrations at which the analog saturates both binding sites. Since occupancy of the cAMP-binding sites by this derivative apparently did not lead to activation of the enzyme, we examined whether this compound could antagonize the activation by cAMP. Indeed (Rp)-cAMPS was found to inhibit cAMP stimulated kinase activity at concentrations compatible to its binding affinity. Also with mammalian protein kinase type II (Rp)-cAMPS showed antagonistic activity, while with a cAMP-dependent protein kinase from Dictyostelium discoideum partial agonistic activity was observed. Previously a mechanism for activation of protein kinase type I was proposed involving a charge interaction between the equatorial exocyclic oxygen atom and the binding site [De Wit et. al. (1982) Eur. J. Biochem 122, 95-99]. This was based on measurements with impure preparations of (Rp)-cAMPS and the Rp and Sp isomers adenosine 3', 5'-monophosphodimethylamidate. cAMPN(CH3)2. The present work using highly purified compounds suggests the absence of a charge interaction, since the uncharged analog (Sp)-cAMPN(CH3)2 activates the kinase effectively. The data seem compatible with an activation model involving the formation of a covalent bond with phosphorus in both cAMP binding sites.


Intermittent heat exposure and thirst in rats.
Adequate water intake, supporting both cardiovascular function and evaporative cooling, is a critical factor in mitigating the effects of heat waves, which are expected to increase with global warming. However, the regulation of water intake during periods of intermittent heat exposure is not well understood. In this study, the effects of access to water or no access during intermittent heat exposure were assessed using male Sprague-Dawley rats exposed to 37.5°C for 4 h/day. After 7 days of intermittent heat exposure, reductions in evaporative water loss were observed in all animals and reductions in water intake following heat exposure occurred as the days of heat exposure increased. Rats that were not allowed water during the 7 days of exposure had decreased rehydration levels, however, rats allowed access to water increased water intake during exposure and exhibited higher overall rehydration levels over the same time period. Peripheral administration of angiotensinII, mimicking activation of volemic thirst, or hypertonic saline solution, activating intracellular thirst, did not result in alteration of water intake in rats exposed to heat with access to water compared to control rats. In contrast, rats exposed to heat without access to water had reduced water intake after administration of hypertonic saline and increased water intake after administration of angiotensinIIcompared to control rats. These experiments demonstrate that thirst responses to intermittent heat exposure are altered by providing water during heat exposure and that intermittent heat exposure without access to water alters drinking responses to both intracellular and extracellular thirst challenges.


Verrucous carcinoma of the female breast.
Verrucous carcinoma is a rare skin malignancy of squamous cell origin. It is characterised by negligible cellular atypia and a low mitotic rate. These are reflected in slow locally invasive behaviour and very infrequent metastatic spread. The tumour is also recognised in oral and anogenital sites. Cutaneous lesions present most commonly on the sole of the foot. We report a unique case occurring in the female breast.


Evaluation of In Situ Antiaging Activity in Saccharomyces cerevisiae BY611 Yeast Cells Treated with Polyalthia longifolia Leaf Methanolic Extract (PLME) Using Different Microscopic Approaches: A Morphology-Based Evaluation.
Polyalthia longifolia is known for its anti-oxidative properties, which might contribute to the antiaging action. Hence, the current research was conducted to evaluate the antiaging activity of P. longifolia leaf methanolic extract (PLME) in a yeast model based on morphology using microscopic approaches. Saccharomyces cerevisiae BY611 strain yeast cells were treated with 1.00 mg/mL of PLME. The antiaging activity was assessed by determining the replicative lifespan, total lifespan, vacuole morphology by light microscopy, extra-morphology by scanning (SEM), and intra-morphology by transmission (TEM) electron microscopy. The findings demonstrated that PLME treatment significantly accelerated the replicative and total lifespan of the yeast cells. PLME treatment also delays the formation of large apoptotic-like type 3 yeast cell vacuoles. The untreated yeast cells demonstrated aging morphology via SEM analysis, such as shrinking, regional invaginations, and wrinkled cell surface. The TEM analysis revealed the quintessential aging intracellular morphology such as swollen, wrinkled, or damaged vacuole formation of the circular endoplasmic reticulum, a rupture in the nuclear membrane, fragmentation of the nucleus, and complete damaged cytoplasm. Decisively, the present study revealed the vital role of PLME in the induction of antiaging activity in a yeast model using three microscopic approaches—SEM, TEM, and bright-field light microscope.


Establish a Digital Real-Time Learning System With Push Notifications.
This study proposes a push notification system that combines digital real-time learning, roll-call, and feedback collection functions. With the gradually flourishing online real-time learning systems, this research further builds roll-call and feedback functions for students to enhance concentration and provide opinions. Additionally, the lecturers can do a roll call irregularly and randomly through the push notification function, avoiding students logging in but away from the keyboard. Lecturers can also send questions to a specific student or invite all students to answer; the replies can show students' learning performance. The system will store each notification in a database and analyse messages automatically to record roll calls. Moreover, the system can record the time and intervals of student feedback, enabling lecturers to check students' attention and learning conditions. Currently, most online digital systems depend on the lecturer to be responsible for the entire system; taking a roll call and asking questions will consume the lecturer's teaching time and strength. The system developed in this article can do roll calls and feedback by push notifications, reducing lecturers' workload. Furthermore, the roll-call and automatic record functions can save the time of paperwork after a course.


DWI Reversibility after Intra-Arterial Thrombolysis. A Case Report and Literature Review.
We report our case and review the literature on reversal DWI lesions, ADC thresholds and correlation between DWI lesion and outcome measured with clinical scales. A 30-years old woman was admitted to our hospital 18 hours after stroke onset. Considering the absence of alterations on CT and the worsening of symptomatology, the patient underwent MRI, which showed a slightly hyperintense signal in FLAIR images in the left portion of the pons and midbrain and a more evident bilateral DWI hyperintensity of the pons. The patient was treated with mechanical and pharmacological intra-arterial thrombolysis. The patient showed a rapid improvement of symptoms. Two weeks after the treatment her clinical conditions were characterized by a residual right hemiparesis and complete recovery of right motility, respiratory and swallowing difficulties. MR examination demonstrated a slight signal alteration of the pons left hemiportion and a disappearance of the mesencephalic signal alteration and of the right portion of the pons. DWI lesions represent irreversibly damaged tissue but new evidence suggests that DWI lesions may be reversible, especially with reperfusion, by now well demonstrated in animal models. Therefore acute DWI lesions probably contain not only irreversibly injured tissue but also parts of the penumbra. The debate on the capability of ADC maps to discriminate irreversibly from reversibly damaged tissue is a matter of controversy. ADC values in human stoke are not an independent indicator of tissue viability. The use of thresholds may improve reproducibility but not validity.


Radiologic case study. Primary lymphoma of bone.
Distinguishing primary lymphoma of bone from disseminated lymphoma and similar appearing bone malignancies is important because of its better prognosis. It is also important to remember how indolent the process can be even in the face of massive bone involvement. Early recognition of this rare entity can increase patient survival.


Genomic Characterization of WRKY Transcription Factors Related to Andrographolide Biosynthesis in Andrographis paniculata.
Andrographolide, which is enriched in the leaves of Andrographis paniculata, has been known as "natural antibiotic" due to its pharmacological activities such as anti-inflammatory, antimicrobial and antioxidant effects. Several key enzymes in andrographolide biosynthetic pathway have been studied since the genome sequences were released, but its regulatory mechanism remains unknown. WRKY transcription factors proteins have been reported to regulate plant secondary metabolism, development as well as biotic and abiotic stresses. Here, WRKY transcription factors related to andrographolide biosynthesis were systematically identified, including sequences alignment, phylogenetic analysis, chromosomal distribution, gene structure, conserved motifs, synteny, alternative splicing event and Gene ontology (GO) annotation. A total of 58 WRKYs were identified in Chuanxinlian genome and phylogenetically classified into three groups. Moreover, nine WRKY genes underwent alternative splicing events. Furthermore, the combination of binding site prediction, gene-specific expression patterns, and phylogenetic analysis suggested that 7 WRKYs (ApWRKY01, ApWRKY08, ApWRKY12, ApWRKY14, ApWRKY19, ApWRKY20, and ApWRKY50) might regulate andrographolide biosynthesis. This study laid a foundation for understanding the regulatory mechanism of andrographolide biosynthesis and the improvement and breeding of Andrographis paniculata varieties.


What should we do with asymptomatic carotid stenosis?
The benefit of prophylactic carotid endarterectomy (CEA) for patients with asymptomatic severe carotid stenosis in the major randomised surgical studies was small, expensive and may now be absorbed by improvements in best practice medical intervention. Strategies to identify patients with high stroke risk are needed. If surgical intervention is to be considered the complication rates of individual surgeons should be available. Clinicians will differ in their interpretation of the same published data. Maintaining professional relationships with clinicians from different disciplines often involves compromise. As such, the management of a patient will, in part, depend on what kind of specialist the patient is referred to. The clinician's discussion with patients about this complex issue must be flexible to accommodate differing patient expectations. Ideally, patients prepared to undergo surgical procedures should be monitored in a trial setting or as part of an audited review process to increase our understanding of current practice outcomes.


Tetralogy of Fallot repair in patients presenting after Infancy: A single surgeon experience.
To determine the early surgical outcomes of Tetralogy of Fallot (TOF) repair in children and young adults operated after the age of one year. In this retrospective study, 307 cases of primary repair of Tetralogy of Fallot were done between September 2012 to February 2017, at CPE Institute of cardiology, Multan. Out of 307 operated patients, 4 (1.3%) patients had previous modified Blalock Taussig shunts, 2 (0.6%) associated ASD with TOF, 3 (0.9%) co-association of TOF with PDA, 2 (0.6%) had large conal arterial branch crossing the annulus, 3 (0.9%) had dextrocardia with situs inversus, 12 (3.9%) TOF with double outlet right ventricle (DORV), 2 (0.6%) were associated with complete AV canal defect, 8 (2.60%) with absent pulmonary valve syndrome, 15 (5.5%) with left pulmonary artery stenosis. Data of post-operative complications and operative parameters was recorded for all patients. Mean age of operated patients was 9.56±4.89 years. Post-operative complications occurred in 7.8% of patients. Most common post-operative complications were pleural effusion with a frequency of 12(3.9%) patients, and complete heart block in one patient. Insignificant small residual VSD was diagnosed in 8 (2.6%) patients. One moderately large VSD was closed surgically after one year of 1st surgery. Moderate to severe pulmonary valve regurgitation was diagnosed in 114 (37.1%) patients. Mild to moderate tricuspid regurgitation in 15 (4.8%) patients and moderate right ventricular outflow tract obstruction (RVOT) in 16 (5.2%) patients. Thirty-day mortality was only four (1.3%). Surgical correction of Tetralogy of Fallot (TOF) in children after one year carries good operative outcomes with minimum morbidity and mortality.


Exploring the eukaryotic Yip and REEP/Yop superfamily of membrane-shaping adapter proteins (MSAPs): A cacophony or harmony of structure and function?
Polytopic cargo proteins are synthesized and exported along the secretory pathway from the endoplasmic reticulum (ER), through the Golgi apparatus, with eventual insertion into the plasma membrane (PM). While searching for proteins that could enhance cell surface expression of olfactory receptors, a new family of proteins termed "receptor expression-enhancing proteins" or REEPs were identified. These membrane-shaping hairpin proteins serve as adapters, interacting with intracellular transport machinery, to regulate cargo protein trafficking. However, REEPs belong to a larger family of proteins, the Yip (Ypt-interacting protein) family, conserved in yeast and higher eukaryotes. To date, eighteen mammalian Yip family members, divided into four subfamilies (Yipf, REEP, Yif, and PRAF), have been identified. Yeast research has revealed many intriguing aspects of yeast Yip function, functions that have not completely been explored with mammalian Yip family members. This review and analysis will clarify the different Yip family nomenclature that have encumbered prior comparisons between yeast, plants, and eukaryotic family members, to provide a more complete understanding of their interacting proteins, membrane topology, organelle localization, and role as regulators of cargo trafficking and localization. In addition, the biological role of membrane shaping and sensing hairpin and amphipathic helical domains of various Yip proteins and their potential cellular functions will be described. Lastly, this review will discuss the concept of Yip proteins as members of a larger superfamily of membrane-shaping adapter proteins (MSAPs), proteins that both shape membranes via membrane-sensing and hairpin insertion, and well as act as adapters for protein-protein interactions. MSAPs are defined by their localization to specific membranes, ability to alter membrane structure, interactions with other proteins via specific domains, and specific interactions/effects on cargo proteins.


Probable posttraumatic stress disorder and women's use of aggression in intimate relationships: the moderating role of alcohol dependence.
Posttraumatic stress disorder (PTSD) is highly prevalent among individuals who experience intimate partner violence (IPV) and is associated with aggression in intimate relationships. The present study examined whether alcohol dependence (AD) attenuates the relation between PTSD and IPV-victimized women's use of physical, psychological, and sexual aggression. Participants were recruited from the community and included 147 women who engaged in substance use and experienced IPV (80.3% Black; M age = 38.24 years, SD = 10.62; M income = $14,323, SD = $12,832). Women with (vs. without) AD reported using significantly more physical and psychological aggression (ηp (2) = .12 and .03, respectively). The probable PTSD × AD interaction emerged as a significant correlate of physical and sexual aggression (ηp (2) = .03). Post hoc analyses revealed higher levels of physical aggression among women with probable PTSD and AD and no-PTSD and AD compared to women with probable PTSD and no-AD (Cohen's ds = 1.09 and 0.63, respectively) and women without PTSD and no-AD (Cohen's ds = 0.92 and 0.60, respectively). Further, women with PTSD and AD reported higher levels of sexual aggression than women without PTSD and AD (Cohen's d = 0.80). Findings suggest the utility of identifying and treating PTSD-AD among IPV-victimized women.


Targeting transcription factors for therapeutic benefit.
Transcription factors are a large class of biological molecules that are important for health and disease. Despite that there are challenges to targeting them therapeutically and most approaches alter their activity indirectly. Research at the chemical biology interface has led to the development of new ways of targeting transcription factors including blocking transcription factor dimerisation, targeting specific DNA sequences and DNA decoys. This review discusses these issues with a view to inspiring the development of new agents that could be useful for the treatment of cancer.


Specific chemoimmunotherapy in tumor-bearing mice with extracted antigen, cyclophosphamide, and intrasplenic administration of interleukin-2.
The effect of daily intrasplenic (I-SP) injection of interleukin-2 (IL-2) in conjunction with specific chemoimmunotherapy with extracted tumor antigens and cyclophosphamide was assessed with the use of methylcholanthrene (MCA)-induced fibrosarcoma in C3H/HeJ mice. Injections of 80 U of human IL-2 were delivered transcutaneously into the spleen (I-SP), which had been relocated to the subcutis with its blood supply intact. Six daily I-SP injections into mice bearing MCA-F tumors activated immune spleen cells (SPC), as evidenced by specific neutralization of the MCA-F, but not the antigenically different MCA-D tumor, in local adoptive transfer assays. The immune cell phenotype was Thy 1.2+ Lyt 2+, based upon abrogation of tumor neutralization after depletion with monoclonal antibodies and complement. In a second series of experiments, primary hosts bearing established MCA-F tumors underwent therapy with 1 microgram 1-butanol extracted, isoelectrophoretically purified TSTA injected subcutaneously, a single intraperitoneal (IP) dose of 20 mg/kg cyclophosphamide (CY), and/or either IP or I-SP IL-2 injection. Triple chemoimmunotherapy with I-SP, but not IP, IL-2 retarded tumor outgrowth more effectively than single or double treatment protocols. Furthermore, in a third series of investigations, the triple therapy group showed both decreased numbers and incidence of spontaneous metastases from a subcutaneous implant of clone 9-4, a highly metastatic variant of MCA-F. Indeed, 35% of hosts that received triple therapy, but none of the animals treated with other regimens, were free of lung metastasis (P less than 0.02). Thus, tumor resistance engendered by chemoimmunotherapy with TSTA and CY is potentiated in vivo by I-SP administration of IL-2.


Sex differences in radioulnar contrasts of the finger ridge counts across 21 human population samples.
Aim: The aim of the present study was to demonstrate the existence of uniform sexual dimorphism in some radioulnar contrasts between different finger ridge counts within the same hand in a large set of populations, thus confirming the universal nature of this dimorphism in humans.Subjects and methods: We analysed individual finger ridge counts (10 values on each hand) of both hands from archival sources (mainly the Brehme-Jantz database). In total, these included 4412 adults from 21 population samples covering all permanently inhabited continents and encompassing very different and geographically distant human populations. We calculated the contrasts (differences) of all pairs of ridge counts (45 per hand) and used diverse methods to assess the direction and degree of dimorphism of them across all population samples.Results: The highest sexual dimorphism was observed for nine contrasts involving the ridge count of the dermatoglyphic pattern on the radial side of the second finger of the right hand (R2r). Among these contrasts, we then found four that had the same direction of dimorphism in all 21 populations. The most dimorphic was the contrast R1rR2r - the difference between the ridge count of the radial side of the thumb and the radial side of the index finger.Discussion: Thus, these dermatoglyphic traits can be further investigated as potential markers of prenatal sex differentiation from ca. 10th week of intrauterine development. However, it will be useful to address the detailed factors and mechanisms for differences in the degree of dimorphism of these traits in different populations.


Rho-like GTPases: their role in cell adhesion and invasion.
Metastasis formation is the leading cause of death in cancer patients. Using an in vitro model system, we have identified Tiam1 (T-lymphoma invasion and metastasis 1) as a gene that can induce invasion by and metastasis of mouse T-lymphoma cells. Subsequent studies showed that Tiam1 is a guanine nucleotide exchange factor for the Rho-like GTPase Rac1, a member of the Ras superfamily of small GTP-binding proteins. Rho-like GTPases play a pivotal role in the orchestration of changes in the actin cytoskeleton in response to receptor stimulation, but have also been shown to be involved in transcriptional activation and cell cycle regulation. Moreover, they can induce oncogenic transformation in fibroblast cells. In this chapter, we first summarize what is known about the signalling pathways that are activated by Tiam1 and Rho-like GTPases, and discuss the putative effectors that may mediate the effects in different cell types. In the latter part, we will more tentatively discuss the role of Tiam1 and Rho-like GTPases in invasion by and metastasis of tumour cells.


Newly developed hybrid assistive limb for pediatric patients with cerebral palsy: a case report.
[Purpose] The effect of fitness training on improving walking ability in cerebral palsy is controversial. However, gait training with a wearable robot (hybrid assistive limb) has been reported to improve gait ability in patients with cerebral palsy. For pediatric patients, a smaller, lighter-weight hybrid assistive limb has been newly developed. We describe the immediate effect of this newly developed smaller hybrid assistive limb on the gait ability of a pediatric patient with cerebral palsy and examine its safety and feasibility. [Participant and Methods] An 11-year-old male with spastic cerebral palsy (height, 130 cm; weight, 29.0 kg) who could ambulate using an elbow crutch participated in this study. A single session of hybrid assistive limb training comprising pre-exercise of the hip and knee joints and walking for 20 minutes was conducted. [Results] The intervention immediately improved his gait speed, stride length, and cadence according to the 10-m walking test. Co-contraction of agonist/antagonist muscles during walking improved, and the flexion angle of the right hip during the swing phase increased, which resulted in symmetry of movement of both legs. [Conclusion] Gait training using the new, smaller hybrid assistive limb for a pediatric patient was safe and feasible, and the newly developed hybrid assistive limb has the potential to immediately improve walking ability even among young children with cerebral palsy.


Basic regulatory parameters of the host-parasite system for warble flies of farm animals using Hypoderma bovis as an example.
While studying the consistent patterns in the host-parasite relationships on the model of warble flies infesting cattle, a firm internal regulatory system governing the number of parasites on the host and reflected in the level of populations, has been demonstrated. This regulatory system is governed by mathematical-statistical laws and therefore can be modelled and its different features expressed mathematically. The distribution of parasites in the host population agrees with the negative binomial distribution. Main mathematical formulations of the regulatory system (parameters) and defensive responses of the host to the invasion of parasites are analyzed. From the above consistent patterns important conclusions are drawn for the control of cattle hypodermatosis in practice. The mathematical model elucidates two states of control--the first stage conforms to the natural regulatory system leading to a marked decrease of the degree of infestation, and the second stage is aiming at the eradication of the disease. It may be deduced from the above said that the control of hypodermatosis is expedient primarily in juvenile cattle, as shown by the results of the control carried out in Czechoslovakia.


The European Vulvovaginal Epidemiological Survey (EVES). Impact of history of breast cancer on prevalence, symptoms, sexual function and quality of life related to vulvovaginal atrophy.
Women with history of breast cancer (HBC) frequently suffer from vulvovaginal atrophy (VVA). European Vulvovaginal Epidemiology Survey (EVES) sub-analysis assesses the impact of HBC on VVA, sexual life and quality of life (QoL) in postmenopausal women. Women with at least one VVA symptom aged 45-75 years were included. EuroQol (EQ-5D-3L) and Day-to-Day Impact of Vaginal Aging (DIVA) questionnaires were filled to investigate QoL. VVA diagnosis was confirmed with objective gynecological examination. Comparison of postmenopausal women with and without HBC, and evaluation of treatment impact on VVA were performed. 1985 postmenopausal women without HBC and 175 with HBC were included. VVA was confirmed in 90.4% of women without HBC and 91.4% of women with HBC. There were no differences in VVA symptoms severity or vulvovaginal discomfort between groups. However, women with HBC who had completed treatment and had surgery 11-20 years previously versus those without HBC presented significantly worse Vaginal Health Index scores, as well as a higher prevalence of VVA objective diagnosis, although their overall symptom severity score was lower. Health status and QoL comparisons were similar. Results support a similar burden in terms of VVA prevalence and symptoms, QoL and sexual function in postmenopausal women with and without HBC.


[A case of complete self-mutilation of penis].
Self-mutilation of the penis is extremely rare. A 69-year-old man was admitted after having amputated his own penis completely from its root. He had no history of psychiatric illness, but his physical condition on admission was abnormal. We performed urethrocutaneostomy, rather than replantation of the penis, because of the danger that he would reinjure himself. The patient was treated by a psychiatrist under a diagnosis of alcoholic dementia. To our knowledge, this is the 24th case of self-mutilation of the penis reported in the Japanese literature.


Treatment of relapsed/refractory acute lymphoblastic leukemia.
Patients with relapsed or refractory acute lymphoblastic leukemia (R/R ALL) have dismal outcomes, with survival of less than 6 months, and treatment options in the salvage setting have been limited to conventional cytotoxic chemotherapy with minimal activity. Advances in the development of novel targeted therapies have significantly improved outcomes in R/R ALL. Blinatumomab, inotuzumab ozogamicin, and chimeric antigen receptor (CAR) T-cell therapy constitute new treatment modalities that are challenging the historical regimens and paving a new path for treating patients with R/R ALL.


Yersinia pestis strains of ancient phylogenetic branch 0.ANT are widely spread in the high-mountain plague foci of Kyrgyzstan.
Fifty six Yersinia pestis strains, isolated over the period of more than 50 years in three high-mountain foci of Kyrgyzstan (Tien Shan, Alai, and Talas), have been characterized by means of PCR and single nucleotide polymorphism (SNP) typing methods. Seven of these strains were also characterized by means of whole genome sequencing and genome-wide SNP phylogenetic analysis. It was found that forty two strains belong to 0.ANT2, 0.ANT3 and 0.ANT5 phylogenetic branches. From these, strains of 0.ANT2 and 0.ANT3 branches were earlier detected in China only, whereas 0.ANT5 phylogenetic branch was identified for Y. pestis phylogeny for the first time. According to the results of genome-wide SNP analysis, 0.ANT5 strains are ones of the most closely related to Y. pestis strain responsible for the Justinianic Plague. We have also found out that four of the studied strains belong to the phylogenetic branch 2.MED1, and ten strains from Talas high-mountain focus belong to the phylogenetic branch 0.PE4 (sub-branch 0.PE4t). Established diversity of Y. pestis strains and extensive dissemination of the strains pertaining to the 0.ANT branch confirm the antiquity of the mentioned above plague foci and suggest that strains of the 0.ANT branch, which serve as precursors for all highly virulent Y. pestis strains, had their origin in the Tien Shan mountains.


Immunogenicity and cytoadherence of recombinant heparin binding haemagglutinin (HBHA) of Mycobacterium avium subsp. paratuberculosis: functional promiscuity or a role in virulence?
Mycobacterium avium subsp. paratuberculosis (MAP) is the causative agent of Johne's Disease, a chronic granulomatous enteritis of ruminants. Recently, an association of MAP bacilli with Crohn's disease in humans has been proposed. Due to genetic similarities and serological cross-reactivity of the M. avium complex with other mycobacteria, functional analysis of species-specific proteins may allow new insights into the pathogenesis of mycobacterial diseases. We report production and molecular characterization of the recombinant HBHA from the MAP complex bacilli. The HBHA was expressed in Escherichia coli and Mycobacterium smegmatis using efficient expression vector systems. The recombinant HBHA was found to be immunogenic and therefore induced antibody responses in cattle against the MAP bacilli with a possible cross reactivity with M. bovis infection. The MAP complex HBHA was thus found to be a target of the host humoral responses in Johne's disease. The recombinant HBHA protein was also found to be adherent to the Caco2 cell lines in-vitro, a significant observation to understand possible virulence mechanisms. Since M. tuberculosis HBHA was earlier shown to be involved in dissemination of the tubercle bacilli, the immunogenicity and cytoadherent nature of this MAP protein possibly suggests functional promiscuity.


Exploring the physical health of patients with severe or long-term mental illness using routinely collected general practice data from MedicineInsight.
Australian information on the physical health of general practice patients with a mental illness is limited. The aim of this study was to explore the physical health of patients with a severe and/or long-term mental illness (SMI). Analysis was performed of routinely collected data from patients visiting one of 452 general practice sites participating in the national MedicineInsight program during 2017-18. Of the 173,861 participants, 9.1% had recorded SMI. Almost three-quarters had a record of the selected long-term physical health conditions, compared with half of patients without recorded SMI (adjusted odds ratio: 2.2, 95% confidence interval: 2.1, 2.3). Patients with SMI were also more likely to have a history of smoking or moderate-to-heavy drinking. More patients with SMI had records of the investigated health conditions than those without SMI. They also had higher rates of modifiable risk factors. As patients with SMI are likely to visit their general practitioners often, this presents an opportunity for intervention that may improve patient outcomes.


Region-selective effects of neuroinflammation and antioxidant treatment on peripheral benzodiazepine receptors and NMDA receptors in the rat brain.
Following induction of acute neuroinflammation by intracisternal injection of endotoxin (lipopolysaccharide) in rats, quantitative autoradiography was used to assess the regional level of microglial activation and glutamate (NMDA) receptor binding. The possible protective action of the antioxidant phenyl-tert-butyl nitrone in this model was tested by administering the drug in the drinking water for 6 days starting 24 hafter endotoxin injection. Animals were killed 7 days post-injection and consecutive cryostat brain sections labeled with [3H]PK11195 as a marker of activated microglia and [125I]iodoMK801 as a marker of the open-channel, activated state of NMDA receptors. Lipopolysaccharide increased [3H]PK11195 binding in the brain, with the largest increases (two- to threefold) in temporal and entorhinal cortex, hippocampus, and substantia innominata. A significant (> 50%) decrease in [125I]iodoMK801 binding was found in the same brain regions. Phenyl-tert-butyl nitrone treatment resulted in a partial inhibition (approx. 25% decrease) of the lipopolysaccharide-induced increase in [3H]PK11195 binding but completely reversed the lipopolysaccharide-induced decrease in [125I]iodoMK80 binding in the entorhinal cortex, hippocampus, and substantia innominata. Loss of NMDA receptor function in cortical and hippocampal regions may contribute to the cognitive deficits observed in diseases with a neuroinflammatory component, such as meningitis or Alzheimer's disease.


Coupling Mechanism of Dissipated Energy-Electromagnetic Radiation Energy during Deformation and Fracture of Loaded Composite Coal and Rock.
The nature of composite coal and rock fracture under load is the process of energy conversion inside it, and to explore the coupling mechanism of dissipated energy (DE) and electromagnetic radiation energy (ERE) during the deformation and fracture process of loaded composite coal and rock, based on theoretical mechanics, electromagnetics, and other subject theories, the stress-charge induction signal coupling relationship is deduced and established. On this basis, a coupled mathematical model of dissipated energy-electromagnetic radiation energy (DE-ERE) is established, and uniaxial loading experiments under different loading rates are carried out. The research results show that the energy of the composite coal and rock increases, and the internal free charge transitions from the high-concentration area to the low-concentration area, accumulating charges on the fractured surface, forming a regional electric field, and generating electromagnetic radiation. The change of the charge-induced signal on the surface of the loaded composite coal and rock is phased and has a corresponding relationship with each mechanical phase. Its peak appears earlier than the stress peak. There is a linear relationship between the charge induction signal and stress, and they have a strong correlation, which is consistent with the established mathematical model. The energy conversion characteristics of the composite coal and rock under load have stage characteristics. The elastoplastic period is mostly converted to dissipative energy release, and the increase of plastic deformation leads to rupture. ERE is one of the components of DE. In the early stage of elastoplasticity, the dissipated energy mainly exists in the form of electromagnetic radiation energy, and the change trends of the two are the same. After the peak value, it drops rapidly, and the DE is mainly composed of other destructive energy that causes deformation. The changes in ERE can be used to determine the DE and stress state, providing a new method for preventing coal and rock dynamic disasters.


Reference state and benchmark concepts for better biodiversity conservation in contemporary ecosystems.
Measuring the status and trends of biodiversity is critical for making informed decisions about the conservation, management or restoration of species, habitats and ecosystems. Defining the reference state against which status and change are measured is essential. Typically, reference states describe historical conditions, yet historical conditions are challenging to quantify, may be difficult to falsify, and may no longer be an attainable target in a contemporary ecosystem. We have constructed a conceptual framework to help inform thinking and discussion around the philosophical underpinnings of reference states and guide their application. We characterize currently recognized historical reference states and describe them as Pre-Human, Indigenous Cultural, Pre-Intensification and Hybrid-Historical. We extend the conceptual framework to include contemporary reference states as an alternative theoretical perspective. The contemporary reference state framework is a major conceptual shift that focuses on current ecological patterns and identifies areas with higher biodiversity values relative to other locations within the same ecosystem, regardless of the disturbance history. We acknowledge that past processes play an essential role in driving contemporary patterns of diversity. The specific context for which we design the contemporary conceptual frame is underpinned by an overarching goal-to maximize biodiversity conservation and restoration outcomes in existing ecosystems. The contemporary reference state framework can account for the inherent differences in the diversity of biodiversity values (e.g. native species richness, habitat complexity) across spatial scales, communities and ecosystems. In contrast to historical reference states, contemporary references states are measurable and falsifiable. This 'road map of reference states' offers perspective needed to define and assess the status and trends in biodiversity and habitats. We demonstrate the contemporary reference state concept with an example from south-eastern Australia. Our framework provides a tractable way for policy-makers and practitioners to navigate biodiversity assessments to maximize conservation and restoration outcomes in contemporary ecosystems.


Mitochondrial membrane potential and ATP production in primary disorders of ATP synthase.
Studies of fibroblasts with primary defects in mitochondrial ATP synthase (ATPase) due to heteroplasmic mtDNA mutations in the ATP6 gene, affecting protonophoric function or synthesis of subunit a, show that at high mutation loads, mitochondrial membrane potential DeltaPsi(m) at state 4 is normal, but ADP-induced discharge of DeltaPsi(m) is impaired and ATP synthesis at state 3-ADP is decreased. Increased DeltaPsi(m) and low ATP synthesis is also found when the ATPase content is diminished by altered biogenesis of the enzyme complex. Irrespective of the different pathogenic mechanisms, elevated DeltaPsi(m) in primary ATPase disorders could increase mitochondrial production of reactive oxygen species and decrease energy provision.


Does globalization mitigate environmental degradation in selected emerging economies? assessment of the role of financial development, economic growth, renewable energy consumption and urbanization.
While the acceleration of globalization in newly developing (emerging) economies contributes positively to economic developments on the one hand, it is a research topic that can have an impact on environmental pollution on the other hand. Therefore, this study analyzes the impact of globalization on environmental pollution for 14 emerging economies in the 1991-2018 period by including economic growth, financial development, renewable energy consumption, and urbanization in the ecological footprint model. In addition to the AMG forecaster, Driscoll-Kraay, PCSE, and FGLS estimation techniques are used for long-term forecasting. Causal linkages among variables are analyzed by the Dumitrescu-Hurlin panel bootstrap causality test. The findings show that the series are cointegrated, that is, a long-term relationship between the variables. In the long term, globalization and renewable energy consumption reduce environmental pollution, while economic growth and financial development play a role in encouraging environmental pollution. Causality analysis enumerates a causality from economic growth and financial development to environmental pollution, as well as a two-way causality between globalization and environmental pollution and renewable energy consumption and environmental pollution. Empirical findings can offer important implications for policies that will reduce environmental pollution in these countries.


In vitro modulation of alkaline phosphatase activity in neutrophils from patients with chronic myelogenous leukemia by monocyte-derived activity.
To clarify the underlying mechanism of low neutrophil alkaline phosphatase (NAP) activity in chronic myelogenous leukemia (CML), CML neutrophils were cultured in liquid medium with different numbers of monocytes. Alkaline phosphatase activity in CML neutrophils, assessed cytochemically, increased with the numbers of monocytes. NAP activity was not induced by the interaction between neutrophils and monocytes, but by the presence of a monocyte-derived soluble activity. NAP activity in normal neutrophils was also lowered by depletion of monocytes from culture medium. Under such monocyte-depleted conditions, both CML and normal neutrophils proliferated and differentiated to produce mature neutrophils. Thus induction of NAP activity can be modified in vitro by changing the amount of NAP-inducing activity released from monocytes. However, whether a reduction of NAP-inducing activity in CML neutrophil is the cause of low NAP activity in vivo remains uncertain.


Biochemical study of the anti-diabetic action of the Egyptian plants fenugreek and balanites.
Fenugreek and Balanites are two plants commonly used in Egyptian folk medicine as hypoglycemic agents. In the present study, the effects of 21 days oral administration of Fenugreek seed and Balanites fruit extracts (1.5 g/kg bw) on the liver and kidney glycogen content and on some key liver enzymes of carbohydrate metabolism in STZ-diabetic rats were studied. In addition, the effects of these two plant extracts on the intestinal alpha-amylase activity in vitro and starch digestion and absorption in vivo were also examined. Results indicated that single injection of STZ (50 mg/kg bw) caused 5-folds increase in the blood glucose level, 80% reduction in serum insulin level, 58% decrease in liver glycogen and 7-folds increase in kidney glycogen content as compared to the normal levels. The activity of glucose-6-phosphatase was markedly increased, whereas, the activities of both glucose-6-phosphate dehydrogenase and phospho-fructokinase were significantly decreased in the diabetic rat liver. Administration of Fenugreek extract to STZ-diabetic rats reduced blood glucose level by 58%, restored liver glycogen content and significantly decreased kidney glycogen as well as liver glucose-6-phosphatase activity. Meanwhile, Balanites extract reduced blood glucose level by 24% and significantly decreased liver glucose-6-phosphatase activity in diabetic rats. On the other hand, our results demonstrated that both the Fenugreek and Balanites extracts were able to in vitro inhibit alpha-amylase activity in dose-dependent manner. Fenugreek was more potent inhibitor than Balanites. This inhibition was reversed by increasing substrate concentration in a pattern which complies well with the effect of competitive inhibitors. Furthermore, this in vitro inhibition was confirmed by in vivo suppression of starch digestion and absorption induced by both plant extracts in normal rats. These findings suggest that the hypoglycemic effect of Fenugreek and Balanites is mediated through insulinomimetic effect as well as inhibition of intestinal alpha-amylase activity.


Testing an application of a biotic ligand model to predict acute toxicity of metal mixtures to rainbow trout.
The authors tested the applicability of a previously developed biotic ligand model (BLM) to predict acute toxicity of single metals and metal mixtures (cadmium, lead, and zinc) to rainbow trout fry (Oncorhynchus mykiss) from a single available dataset. The BLM used in the present study hypothesizes that metals inhibit an essential cation (calcium) and organisms die as a result of its deficiency, leading to an assumption that the proportion of metal-binding ligand (f) is responsible for the toxic effects of metals on the survival of rainbow trout. The f value is a function of free-ion concentrations of metals computed by a chemical speciation model, and the function has affinity constants as model parameters. First, the survival effects of single metals were statistically modeled separately (i.e., f-survival relationship) by using the generalized linear mixed model with binomial distribution. The modeled responses of survival rates to f overlapped reasonably irrespective of metals tested, supporting the theoretical prediction from the BLM that f-survival relationships are comparable regardless of metal species. The authors thus developed the generalized linear mixed model based on all data pooled across the single-metal tests. The best-fitted model well predicted the survival responses observed in mixture tests (r = 0.97), providing support for the applicability of the BLM to predict effects of metal mixtures.


[Clinical feature of organophosphate poisoning patients requiring prolonged mechanical ventilation].
To clarify the clinical characteristics in organophosphate poisoning patients who require prolonged mechanical ventilation (PMV). We reviewed the medical records of 15 adults organophsophate poisoning patients who admitted to our intensive care unit between Junuary, 1995, and December, 2004. The patients were divided into two groups: a PMV group requiring mechanical ventilation for more than 1 week (n=7) and a non PMV group (n=8), and various factors relating to PMV were compared between the two groups. The mean value of mechanical ventilation days was 16 +/- 6 days for the PMV group, which was significantly greater than 1 +/- 1 days for the non PMV group (p < 0.01). There were no statistical differences in the physical findings such as Japan Coma Scale, vital signs, and salivation and/or diarrhea, and in the treatments such as gastric lavage, administration of activated charcoal, and intravenous administration of pralidoxim and/or atropine on admission between the groups. The intermediate syndrome developed in 5 patients of the PMV group during their hospital course, whereas in no patient of the non-PMV group (p < 0.05). Hospital length of stay was 35 +/- 7 days in the PMV group, comparing with 11 +/- 11 days in the non-PMV group (p < 0.01). All patients of both groups survived and all but one patient returned to pre-hospital activities of daily living. Organophosphate poisoning patients requiring PMV had a higher incidence of the intermediate syndrome, but had similar mortality and morbidity compared with patients without PMV.


Mechanisms of electrical field stimulation-induced vasodilatation in the guinea-pig basilar artery: the role of endothelium.
1. The role of endothelium in neuronal vasodilatation elicited by electrical field stimulation (EFS) was investigated in preparations of the isolated guinea-pig basilar artery in which the tone was raised with prostaglandin F2 alpha. 2. In preparations with intact endothelium, EFS produced frequency-dependent dilatations which were not affected by guanethidine but were slightly yet significantly reduced by atropine (1 microM), and were blocked by tetrodotoxin (1 microM) and the nitric oxide synthase inhibitor L-NAME (10 microM). 3. Dilatations were elicited by acetylcholine (3 microM); these were blocked by L-NAME and atropine (1 microM). 4. Dilatations were elicited by nicotine (100 microM); these were blocked by L-NAME and hexamethonium (100 microM). 5. Dilation elicited by sodium nitroprusside (SNP, 3 microM) was not affected by L-NAME. 6. The inhibitory effects of L-NAME were partially prevented by L-arginine (1 microM). 7. Removal of the endothelium resulted in a significant reduction of dilatations elicited by EFS, elimination of the dilator action of acetylcholine, but enhancement of that to SNP. 8. The results suggest that EFS-induced vasodilatation is mediated in part by the nitrergic transmitter and in part endothelium derived relaxing factor (EDRF) activated by acetylcholine released from cholinergic nerves.


High-Crystalline Monolayer Transition Metal Dichalcogenides Films for Wafer-Scale Electronics.
Chemical vapor deposition (CVD) using liquid-phase precursors has emerged as a viable technique for synthesizing uniform large-area transition metal dichalcogenide (TMD) thin films. However, the liquid-phase precursor-assisted growth process typically suffers from small-sized grains and unreacted transition metal precursor remainders, resulting in lower-quality TMDs. Moreover, synthesizing large-area TMD films with a monolayer thickness is also quite challenging. Herein, we successfully synthesized high-quality large-area monolayer molybdenum diselenide (MoSe2) with good uniformity via promoter-assisted liquid-phase CVD process using the transition metal-containing precursor homogeneously modified with an alkali metal halide. The formation of a reactive transition metal oxyhalide and reduction of the energy barrier of chalcogenization by the alkali metal promoted the growth rate of the TMDs along the in-plane direction, enabling the full coverage of the monolayer MoSe2 film with negligible few-layer regions. Note that the fully selenized monolayer MoSe2 with high crystallinity exhibited superior electrical transport characteristics compared with those reported in previous works using liquid-phase precursors. We further synthesized various other monolayer TMD films, including molybdenum disulfide, tungsten disulfide, and tungsten diselenide, to demonstrate the broad applicability of the proposed approach.


Serological response in rabbits to Listeria monocytogenes after oral or intragastric inoculation.
The serological response in rabbits against Listeria monocytogenes after oral or intragastric inoculation was investigated. Both the number of sero-positive animals and the average serum titres were higher in animals inoculated by the oral route. This difference was especially marked in rabbits inoculated with the lower dose (1 x 10(3) colony-forming units (cfu)), which developed a strong serological response (average serum titre of 1280 after 4 inoculations) in most of the inoculated animals (80%), without any clinical signs. The implication of these results in the epidemiology of listeriosis is discussed.


Calcium polyuronate dressing supplemented with zinc and manganese (trionic®) in necrotizing dermohypodermitis of the extremities: a randomized multicentre study.
Background. For the burn surgeon, the treatment of necrotizing soft tissue infections is one of the most demanding surgical emergencies, requiring "radical excisions" of the infected tissue and reconstruction. During the infection period, the excised sites are treated with application of gauzes soaked in saline solution. When the septic period is over, the excision sites are usually covered by sterile paraffin gauze dressing. Our aim was to evaluate a new calcium polyuronate dressing enriched with zinc and manganese ions (test group) versus the reference therapeutic combination (control group) from the septic period to the grafting of skin. Materials and methods. A multicentre, prospective, controlled, randomized clinical trial was conducted from November 2003 to July 2005. The primary endpoint was the waiting period for carrying out the skin graft and the percentage of grafted patients at 28 days after the last excision. The secondary endpoints were blood loss, exudates amounts, and pain during dressing changes. Results. Twenty-five patients were included, 14 with the new dressing and 11 with the reference therapeutic combination. The average waiting period for skin graft was 18 days in the test group versus 27.1 days in the control group (p = 0.128). All the patients in the test group received their grafts within 28 days after the last excision, compared with 60% (p = 0.043) in the control group. Bleeding during dressing change was statistically lower in the test group: 45.5% of the patients did not bleed compared with 0% in the control group (p = 0.045). Treatments were well tolerated. Conclusion. The properties of this new calcium polyuronate enriched with zinc and manganese ions seem to accelerate granulation tissue development, allowing skin grafting earlier in favourable conditions with less bleeding and less pain during dressing renewal.


Ethnomedicinal uses of plants for the treatment of nervous disorders at the herbal markets of Bojnord, North Khorasan Province, Iran.
Since ancient times, plants have been commonly used to cure human ailments by indigenous people throughout the world. Nervous diseases are rising all around the world. This paper provides important ethnobotanical information on plants that are used against neurological disorders and are available in medicinal markets of Bojnord, northeastern Iran. This survey, as an ethnobotanical study, was carried out between 2017 and 2018. The identification of the intended plant species was done using the available Floras. Some important indices such as the frequency of citations, relative frequency of citation (RFC), family importance value and use report were calculated for the medicinal plants included in the present study. The present study includes 58 medicinal plant species belonging to 36 families and reports their mentioning scientific and vernacular names, parts used, and preparation method. The most common family was Lamiaceae. The major parts of the identified plants used for treatment of nervous )neuropsychological( disorders were flower and aerial parts. The most common methods used for preparation of these plants were infusion and decoction. Stachys turcomanica, Tripleurospermum disciforme, Melissa officinalis, Nardostachys jatamansi, and Aloysia citriodora had the highest rate of use report. Echium amoenum and Melissa officinalis had the highest RFC. The study indicated that although people in Bojnord have access to modern medicinal preparations, a considerable number of them still use medicinal plants for therapeutic purposes. Seemingly, most cited plants are worth more precise evaluations for their pharmacological activity.


Positron emission tomography costs less to patients than conventional screening for malignancy in dermatomyositis.
Dermatomyositis (DM) is associated with malignancy and interstitial lung disease. Many malignancies associated with DM occur in organs not routinely screened by national guidelines; thus, best screening practices are still debated. Positron emission tomography (PET) has been suggested as a single study alternative to more complex screening panels and may also be valuable in detecting interstitial lung disease progression. Criticisms of PET screening exams have focused on cost and radiation exposure. To compare the cost of PET and its variants to conventional malignancy screening panels, and to review concerns regarding radiation exposure in PET. Four variants of PET and PET-CT were included in the study. The conventional screening panel was defined as CT of the abdomen and pelvis without contrast, CT of the thorax without contrast, CEA, CA 19.9, PSA (men), mammography (women), transvaginal ultrasound (women), cytopathology (women), and CA 125 (women). The MarketScan® Commercial Claims and Encounters database, a collection of private insurance claims data from 53 million Americans, was queried for every instance of each test from 2005 to 2014 and the mean inflation-adjusted cost of each was recorded. The mean total cost to insurance companies and the mean out-of-pocket costs to patients for PET variants were compared to the costs for conventional panels. Additionally, the cost of pulmonary function tests (PFT) from the same period was evaluated. From 2005-2014, the mean inflation-adjusted costs of PET have trended downward, but the mean cost of PET-CT have trended upward. The mean total cost to insurance companies for PET-CT whole body was $730.70 and $537.62 greater than the cost of conventional panels for men and women, respectively. The out-of-pocket patient costs for PET-CT whole body was $109.82 and $111.33 less than the cost of conventional panels for men and women, respectively. The mean total cost of PFT was $205.02. The cost of PET-CT whole body was greater than conventional panels for insurance companies, but patient out-of-pocket costs were lower. PET-CT may also have added value in detecting and monitoring interstitial lung disease progression in DM patients. More data are needed on the efficacy of PET-CT in detecting malignancy in DM patients; however, the cost difference is less than expected, suggesting the single scan could be a reasonable alternative to the conventional screening panel in some patients.


Crossreactive recognition of viral, self, and bacterial peptide ligands by human class I-restricted cytotoxic T lymphocyte clonotypes: implications for molecular mimicry in autoimmune disease.
The immunodominant, CD8(+) cytotoxic T lymphocyte (CTL) response to the HLA-B8-restricted peptide, RAKFKQLL, located in the Epstein-Barr virus immediate-early antigen, BZLF1, is characterized by a diverse T cell receptor (TCR) repertoire. Here, we show that this diversity can be partitioned on the basis of crossreactive cytotoxicity patterns involving the recognition of a self peptide-RSKFRQIV-located in a serine/threonine kinase and a bacterial peptide-RRKYKQII-located in Staphylococcus aureus replication initiation protein. Thus CTL clones that recognized the viral, self, and bacterial peptides expressed a highly restricted alphabeta TCR phenotype. The CTL clones that recognized viral and self peptides were more oligoclonal, whereas clones that strictly recognized the viral peptide displayed a diverse TCR profile. Interestingly, the self and bacterial peptides equally were substantially less effective than the cognate viral peptide in sensitizing target cell lysis, and also resulted only in a weak reactivation of memory CTLs in limiting dilution assays, whereas the cognate peptide was highly immunogenic. The described crossreactions show that human antiviral, CD8(+) CTL responses can be shaped by peptide ligands derived from autoantigens and environmental bacterial antigens, thereby providing a firm structural basis for molecular mimicry involving class I-restricted CTLs in the pathogenesis of autoimmune disease.


High-Resolution Dynamics of Hemodilution After Exercise-Related Hemoconcentration.
Hemoconcentration during acute intense exercise is intensively investigated, while the rearrangement of hematological parameters during the recovery period is less understood. The aim of our study was to understand the mechanisms of hemodilution after short-term dynamic exercise. Twelve euhydrated male kayak athletes and 6 untrained controls were examined on a spiroergometer. In addition to the continuous recording of circulatory parameters, blood samples were taken at rest, at maximum load, and during restitution with a dense sampling frequency. Hemoglobin, hematocrit, osmolality, blood components, and core temperature were measured. The hemoconcentration, independently of training status, reached its maximum (athletes Δ9.59% [4.18%] vs controls Δ11.85% [2.71%]) in the first minute of the recovery period. There was a significant increase in core temperature, reducing the viscosity of blood and promoting tissue oxygenation. High cardiac output and the increased blood flow compensate for viscosity being elevated by hemoconcentration during exercise. Hemoconcentration was maintained for 7 to 10 minutes and then diluted back to baseline 30 minutes after exercise. Temporarily higher viscosity during reduced cardiac output may result in a critical hemoconcentration zone, elevating the risk of circulatory overload. Elite athletes have a faster cardiac output decrease compared with that of hemodilution, making the circulation more vulnerable. We supposed that hemodilution was guided independently by plasma- and erythrocyte-related effectors. After high-intensity dynamic acute exercise, hemodilution is driven by independent factors, and a critical hemoconcentration zone may be formed during the recovery period in trained elite athletes.


[The ileocecal vagina].
In 3 patients with vaginal aplasia respectively traumatic vaginal loss a neovagina was created out of the separated ileocecal segment. Advantages of this technique are the excellent blood supply of the ileocecal region and the long vascular pedicle. The additional application of terminal ileum for prolongation of the cecal vaginoplasty allows the tensionless anastomosis between neovagina and vulva even in patients with difficult anatomical conditions. The present paper gives a detailed description of the operative technique and the indications of the ileocecal vaginoplasty. Furthermore the common techniques for vaginal replacement are reviewed and discussed.


Dicarbonyl reduction by single enzyme for the preparation of chiral diols.
Chiral diols are a group of key building blocks useful for preparing a variety of important chiral chemicals. While the preparation of optically pure diols is generally not an easy task in synthetic organic chemistry, three classes of enzymes, namely dicarbonyl reductase, dioxygenase and epoxide hydrolase, display remarkable ability to stereoselectively introduce two hydroxyl groups in a single-step enzymatic conversion. In this tutorial review, we pay special attention to dicarbonyl reductases that directly produce chiral diols through the bio-reduction of two carbonyl groups. The dicarbonyl reductases include diketoreductase, α-acetoxy ketone reductase and sepiapterin reductase. We present these exceptional enzymes in the context of source and properties, structure and catalytic mechanism as well as biocatalytic application. In addition to the broad substrate specificity, the excellent stereoselectivity and high catalytic efficiency of these enzymes have positioned them as valuable biocatalysts. With more sophisticated understanding of the structure-function relationship, the practical utilities of these enzymes associated with their interesting chemistry will be considerably appreciated over time. Moreover, rational redesign and molecular evolution of these unusual biocatalysts will truly enable their broader applications in the synthesis of chiral diols in the future.


[Exposure to mercury and population health. I. Immunotoxicity of mercury].
The authors present large numbers of data on influence of the various mercury compounds on the immune system of humans and laboratory animals. The effect of mercury on the immune system was studied mainly in small rodents intoxicated mostly with HgCl2 or methylmercury. Contrary to a number of these data, analogous observations in humans are rare. Stimulating activity of mercury vapours on the immunological system has been reported in workers at chloralkali plants. So far no data are available concerning influence of the mercury vapours on the resistance of humans to neoplasms and infections.


COVID-19 and its effect on the provision of ophthalmic care in the United Kingdom.
The first quarter of 2020 gave light to a novel virus, Coronavirus 2019 (COVID-19), causing a pandemic of unbridled proportions. The National Health Service in the United Kingdom issued guidance to ensure that capacity was increased in acute medical settings, to prepare for the surge of COVID-19 cases. The Royal College of Ophthalmologists followed suit with guidance on the curtailment of all elective activity, aimed at protecting both patients and staff. Ophthalmology is one of the busiest outpatient specialities, and risk stratification of patients with appointments cancelled or on review lists was paramount to ensure there was no serious, permanent harm to sight. Our way of working, as we knew it, had to change in a short period of time. Local emergency eye care was changed from a walk in service, with the implementation of a strict triage protocol. Ophthalmologists, as well as Otorhinolaryngology colleagues, were identified as being at high risk of infection, due to the close proximity of clinical examination. The redesign of clinical areas to allow for social distancing, slit lamp barriers and personal protective equipment was all implemented. This time of relative pause has provided the opportunity to harness new ways of working, including the streamlining of services, reduction of backlog and the incorporation of telemedicine. Health preparedness is a new lexicon to Ophthalmology departments across the world, and it will now have to be stringently implemented in the ophthalmic setting.


High prevalence of 1762(T) 1764(A) mutations in the basic core promoter of hepatitis B virus isolated from black Africans with hepatocellular carcinoma compared with asymptomatic carriers.
The purpose of this study was to identify mutations in the basic core promoter and enhancer II region of the hepatitis B virus (HBV) that might cause the HBV e antigen (HBeAg)-negative phenotype and contribute to hepatocarcinogenesis in black African carriers of the virus. The basic core promoter/enhancer II overlaps with the X gene. HBV DNA from serum of 47 asymptomatic carriers and 50 patients with hepatocellular carcinoma and from 28 tumor and 10 nontumor liver tissues was amplified and sequenced directly. That part of the enhancer II region not overlapping the basic core promoter was completely conserved in all samples. Missense mutations at nucleotides 1809 and 1812 in the basic core promoter were found in 80% of all sequences and may represent wild-type sequence in Southern African isolates. Nucleotide and amino acid divergences were higher in the basic core promoter of hepatocellular carcinoma patients when compared with asymptomatic carriers (P <.0001). This applied particularly to the paired 1762 adenine to thymine (1762(T)) and 1764 guanine to adenine (1764(A)) missense mutations, the prevalence of which was 66% in patients with hepatocellular carcinoma compared with 11% in asymptomatic carriers (P <.0001). There was no association between the presence of 1762(T) 1764(A) and HBeAg negativity, although these mutations suppressed HBeAg titers in HBeAg-positive patients. Suppression of HBeAg expression as well as alteration of the amino acid sequence of the X protein may play a role in hepatocarcinogenesis.


Different stages of disease detection in squash plant based on machine learning.
To increase agriculture production, accurate and fast detection of plant disease is required. Expert advice is needed to detect disease in plants, nutrition deficiencies or any other abnormalities caused by extreme weather conditions. But this process is very tedious, costly, and takes more time. In this paper, hyperspectral imaging and machine learning were used to detect different stages (early, middle, and critical stage) of the powderly mildew disease (PMD) in squash plants. An unmanned aerial vehicle (UAV) was used to collect the data from the field and Locality Preserving Discriminative Broad Learning (LPDBL) was used to distinguish the diseased and healthy plants. In addition, the ability to detect the diseased plant by the proposed method was evaluated using 10 different spectral vegetation indices (VIs). The results show the proposed method detected the disease accurately in the early, middle, and critical stages of the squash plant. The proposed method's performance is compared with six different PMDs under indoor laboratory test and UAV-based field test conditions. The comparison's results show that the LPDBL provides better accuracy in detecting disease in the squash plant.


A retrospective study of 12 cases of pyoderma gangrenosum: why we should avoid surgical intervention and what therapy to apply.
Lesions of skin are ubiquitous in the medical field. The varying etiopathologies with similar presentation can pose a misleading picture, especially when faced with less common skin diseases. Furthermore, the misdiagnosis can cause detrimental effects on the patient's morbidity and mortality, which was seen in the case series study we performed on pyoderma gangrenosum. The history of 12 patients were analyzed in reference to the course of the disease, accompanying diseases, clinical picture, histopathological examination, surgical intervention before diagnosis, and treatment. Within this group of 12 patients, five were exposed to surgical interventions before diagnosis of pyoderma gangrenosum. The 5 patients were all exposed to prolonged aggravation of the disease process, followed by remission after proper diagnosis and treatment therapy. This study was done to improve the knowledge of surgeons about pyoderma gangrenosum considering the frequency of skin lesion cases in the surgical practice. Knowledge of the disease is essential to diagnose pyoderma gangrenosum in early stages to avoid interventions that may prolong or worsen the outcome. Surgical interventions in these patients should be avoided before proper diagnosis. The key to a better prognosis of pyoderma gangrenosum patients is often in the hands of surgeons.


[Thrombocyte functions in malignant blood diseases].
Platelet aggregation with various inductors and platelet secretion were studied in chronic lymphoid leukemia, myeloma, chronic myeloid leukemia and acute leukemia. It was established that disturbed aggregation with adrenaline and disturbed secretion are found more often in these malignant blood diseases. An interesting fact is that there is no correlation between the disturbed platelet functions in vitro and the clinical manifestations of disturbed hemostasis (hemorrhages or thrombosis).


Reconstitution of anti-HIV effector functions of primary human CD8 T lymphocytes by transfer of HIV-specific alphabeta TCR genes.
We redirected the antigen specificity of primary human CD8 T cells by retrovirus-mediated transduction of genes encoding alphabeta TCR specific to HIV-1 Pol protein. A large polyclonal population of TCR-transduced CD8 T cells showed substantial cytotoxic and cytokine production activities toward target cells either pulsed with the peptide or infected with HIV-1, and their functional activities were comparable to those of the parental CTL clone. Peptide fine-specificity and promiscuous recognition of HLA class I supertypes of the parental CTL clone were also preserved in the TCR-transduced cells. There were no signs of allogeneic responses in these cells, although hybrid TCR dimers consisting of transduced TCR and endogenous TCR were suspected to have been formed in these cells, as the effect of transgene expression on the surface expression of the desired TCR was limited. Moreover, the TCR-transduced cells showed potent inhibitory activity against HIV-1 replication in vitro, although the differential surface expression of the desired TCR resulted in differential functional avidity of individual TCR-transduced cells toward the peptide-pulsed target cells. These data suggest that the reconstitution of HIV-specific immunoreactive T cells engineered by genetic transfer of HIV-specific TCR is a potential alternative to immunotherapeutic applications against HIV infections.


Synthesis and optical properties of gold nanorods with controllable morphology.
Searching for architectural building blocks with tunable morphology and peculiarity is a prominent challenge for novel diagnostic and therapeutic applications. Here, the aqueous-based seed-mediated methods for preparing highly mono-dispersed Au nanorods with a different aspect ratio are systematically studied by controlling the amounts of Ag ions and seeds. We also explore the effect of pH on the synthesis of gold nanorods. The realization of the overlap of longitudinal plasmon band and excitation source with different degrees is made by changing the aspect ratio of nanorod in order to determine its effect on the overall surface enhancement. In addition, the gold octahedra are prepared by overgrowth on Au nanorods. The SERS effects of Au nanorods are researched and the FDTD simulations are performed to reveal the morphology induced plasmon modes.


Oral Mucosal Graft Augmented Anastomotic Urethroplasty for Post Traumatic Urethral Stricture and Distraction Defect: Outcome in 100 Patients.
The surgical procedures of post traumatic posterior urethral stricture and distraction defects range from the extremely simple to the extremely radical. In oral Mucosal Graft Augmented Anastomotic Urethroplasty (OMG AAU) the stricture segment is excised followed by partially re-anastomosis of the dorsal or ventral urethral wall then the reconstruction is completed by placement of oral mucosal graft into the remaining urethral defect. The aim of this study is to determine the impact and assess the effectiveness of this technique, discuss the procedure and outcome and to refine them where found lacking. A prospectively collected review of records was done from September 2010 to April 2019. A total 100 patients with post traumatic urethral stricture and distraction defect were treated by dorsal onlay oral mucosal graft augmented anastomotic urethroplasty by same surgeon in a single centre. All were followed up every 3 and 6 monthly for 1-2 years with uroflowmetry. Retrograde urethrogram/Micturating cysto-urethrogram (RGU/MCU) and cystoscopy were reserved for those who had complained of obstructive symptoms and uroflowmetry evidence of outflow obstruction. The etiology of trauma was road traffic accident (RTA) (69%), falling astride (28%) and traumatic catheterization (3%). Mean excised stricture length was 1.5cm (Range 1.0-2.2). The mean length of dorsal onlay considering excised stricture length and 1cm spatulations was 4.25cm (range 2.0-6.5). The successful recovery was observed in 94% cases. On conclusion the technique of OMG AAU is very easy to do, reliable and has high success rates. This is also the procedure of choice for long segment obliterative strictures. For post traumatic obliterative strictures and distraction defects we strongly recommend the procedure for successful and patient satisfactory outcome.


Rhizospheric microbial communities associated with wild and cultivated frankincense producing Boswellia sacra tree.
Boswellia sacra, a frankincense producing endemic tree, has been well known for its cultural, religious and economic values. However, the tree has been least explored for the associated microsymbiota in the rhizosphere. The current study elucidates the fungal and bacterial communities of the rhizospheric regions of the wild and cultivated B. sacra tree populations through next generation sequencing. The sequence analysis showed the existence of 1006±8.9 and 60.6±3.1 operational taxonomic unit (OTUs) for bacterial and fungal communities respectively. In fungal communities, five major phyla were found with significantly higher abundance of Ascomycota (60.3%) in wild population and Basidiomycota (52%) in cultivated tree rhizospheres. Among bacterial communities, 31 major phyla were found, with significant distribution of Actinobacteria in wild tree rhizospheres, whereas Proteobacteria and Acidobacteria were highly abundant in cultivated trees. The diversity and abundance of microbiome varied significantly depending upon soil characteristics of the three different populations. In addition, significantly higher glucosidases, cellulases and indole-3-acetic acid were found in cultivated tree's rhizospheres as compared to wild tree populations. for these plants to survive the harsh arid-land environmental conditions. The current study is a first comprehensive work and advances our knowledge about the core fungal and bacterial microbial microbiome associated with this economically important tree.


Resonant two-photon ionization spectroscopy of jet-cooled tantalum carbide, TaC.
The optical spectrum of diatomic TaC has been investigated for the first time, with transitions recorded in the range from 17,850 to 20,000 cm(-1). Six bands were rotationally resolved and analyzed to obtain ground and excited state parameters, including band origins, upper and lower state rotational constants and bond lengths, Fermi contact parameter b(F) for the ground state, and lambda doubling parameters for the excited states. The ground state of TaC was found to be X (2)Sigma(+), originating from the 1sigma(2)2sigma(2)1pi(4)3sigma(1) electronic configuration, in which only the valence orbitals arising from the Ta(5d+6s) and C(2s+2p) orbitals are listed. All of the rotationally resolved and analyzed bands were found to originate from the ground state, giving B(0)"=0.489 683(83) cm(-1), r(0)"=1.749 01(15) A, and b(F)"=0.131 20(36) cm(-1) (1sigma error limits) for (181)Ta (12)C. Comparison of the Fermi contact parameter to the atomic value shows that the 3sigma orbital is approximately 75% Ta 6s in character. The other group 5 transition metal carbides, VC and NbC, have long been known to have 1sigma(2)2sigma(2)1pi(4)1delta(1), (2)Delta ground states, with low-lying 1sigma(2)2sigma(2)1pi(4)3sigma(1), (2)Sigma(+) excited states. The emergence of a different ground state in TaC, as compared to VC and NbC, is due to the relativistic stabilization of the 6s orbital in Ta. This lowers the energy of the 6s-like 3sigma orbital in TaC, causing the 1sigma(2)2sigma(2)1pi(4)3sigma(1), (2)Sigma(+) state to fall below the 1sigma(2)2sigma(2)1pi(4)1delta(1), (2)Delta state.