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Normal venous anatomy and collateral pathways in upper extremity venous thrombosis.

Collateral pathways are well known in superior vena cava occlusion but not in axillary or subclavian vein occlusion, even though these occlusions are becoming more common. In a series of 127 arm venograms obtained for suspected venous thrombosis, the authors found 32 instances of subclavian or axillary vein occlusion. The authors reviewed the cases for site of occlusion and definition of collateral pathways. In 15 cases, the occlusion was in the subclavian vein, with collateral flow established chiefly via veins in the neck. Ten cases of axillary vein occlusion with chest wall collateral pathways were identified. Seven cases could not be categorized. Knowledge of these pathways is useful for accurate interpretation of upper extremity venograms. A more thorough understanding of venous pathways in the upper body may aid in the treatment of patients with chronic disease and longterm indwelling central venous catheters.

Arm

Partial enumeration of extreme rays in metabolic networks using bit pattern trees.

Extreme ray analysis of metabolic networks, even though very powerful, is currently limited to smaller metabolic networks. Some approaches to generating partial sets of extreme rays exist, but the computational efficiency of the so-called double-description method is yet to be exploited. Previous work highlighted the possibility of sampling within its iterations, enabling partial enumeration for double-description based methods. However, these approaches severely lack computational efficiency to be a suitable alternative. In this work, the highly efficient bit pattern trees are used within the sampling framework to significantly enhance its output and speed. Combined with the recent revision of the Canonical Basis Approach (CBA), our approach outperforms the other tested methods under the reported benchmark conditions even for a full enumeration study, requiring only half the computation time. In addition, a filter setting allows the memory demand to be scaled down while retaining high efficiency. However, some issues with the combinatorial explosion of candidates still persist and are further investigated. This study therefore puts forward a novel, double description-based alternative to partial enumeration of extreme rays. Further improvements in memory efficiency would allow this promising approach to scale powerful extreme ray-based analyses to genome-scale metabolic networks.

constraint-based modelling

Transposon insertion sequencing of Pseudomonas aeruginosa identifies multiple intersecting pathways essential for extreme colistin resistance.

Colistin is used to treat antibiotic resistant gram-negative infections, including those caused by Pseudomonas aeruginosa (Pa). Using a diverse collection of clinical isolates, we identified BWH047, a colistin-resistant isolate with an extremely high minimum inhibitory concentration (MIC, 1280 µg/mL). To characterize the genes conditionally essential for colistin resistance in BWH047, we employed transposon insertion sequencing and identified 20 gene candidates. In-frame deletion validated 75% of the candidates and identified genes in several new pathways that contribute to colistin resistance in Pa, including algU and wapH. We also identified several candidate genes from previously reported colistin resistance pathways (e.g., arn, pmrAB). We further investigated the impact of a colistin resistance-associated inner membrane DedA-family undecaprenyl phosphate flippase, which we named DpcA (DedA of Pseudomonas necessary for colistin resistance A). Deletion of dpcA in BWH047 restored sensitivity to colistin (MIC = 0.5 µg/mL) and resulted in several unique changes to the structure of lipopolysaccharide (LPS), including production of decreased amounts of the colistin resistance-conferring 4-amino-4-deoxy-L-arabinose (L-Ara4N) modification on lipid A. This work represents a robust analysis of colistin resistance in Pa and identifies intersecting pathways that contribute to extreme phenotypic resistance.

Pseudomonas aeruginosa

Central locomotor programming in the rabbit.

In decorticate, unanaesthetized and curarized rabbit preparations, with both hindlimbs deafferented, locomotor-like discharges were recorded from nerves to flexors and extensors and their time patterns were compared. The bursts of rhythmic activities recorded from nerves to several flexor muscles acting at either joint were shown to be synchronous, with no differences in their time of onset. The same was true for the extensors. Nerves to bifunctional muscles (biceps posterior, semi-tendinosus and tenuissimus) acting on two consecutive joints (knee flexors, hip extensors) could display two consecutive bursts in each locomotor cycle, one being pure flexor and the other an extensor discharge. It is shown here that this functional bivalence is programmed centrally and can be modulated, i.e. the relative importance of the flexor and the extensor bursts can be changed in a predictable way through afferent (proprioceptive or cutaneous) influences, or through activation of the descending monoaminergic pathways. In extreme cases, complete functional reversal was observed in these bifunctional muscle nerves.

Action Potentials

A case of Ph+ acute lymphoblastic leukemia and EGFR mutant lung adenocarcinoma synchronous overlap: may one TKI drug solve two diseases?

BACKGROUND: Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL) refers to ALL patients with t(9;22) cytogenetic abnormalities, accounting for about 25% of ALL. Lung adenocarcinoma (LUAD) is the most common pathological type of non-small-cell lung cancer, which has a frequency of approximately 45% cases with mutations in EGFR. Both Ph+ ALL and EGFR mutant LUAD are involved in the pathogenesis of the abnormal activation of the tyrosine kinase pathway. Although the second primary hematological malignancy after the treatment of solid tumors is common in clinics, the synchronous multiple primary malignant tumors of hematological malignancy overlap solid tumors are uncommon, even both tumors involved in the pathogenesis of the abnormal activation of the tyrosine kinase pathway are extremely rare. CASE PRESENTATION: An 84-year-old man with fatigue and dizziness was diagnosed with Ph+ ALL. Meanwhile, a chest CT indicated a space-occupying lesions, characterized by the presence of void, in the right lower lope with the enlargement of mediastinal lymph node and right pleural effusion. After a few weeks, the patient was diagnosed with LUAD with EGFR exon 19 mutation. Both tyrosine kinase inhibitors (TKI) (Flumatinib) and EGFR-TKI (Oxertinib) was used for the patients, and finally have controlled both diseases. CONCLUSION: As far as we know, we for the first time reported a case of Ph+ ALL and EGFR mutant LUAD synchronous overlap, of which pathogenesis is related to abnormal tyrosine kinase activation. This patient was successfully treated with two different TKIs without serious adverse events.

Humans

The effects of dynamic visual stimulation on perception and motor control.

A set of research findings is described that deals with three principal laboratory measures of visual orientation (vection and postural and manual control). Two studies are highlighted, one of which compared the latencies of vection and visually induced postural change and the other of which investigated manual tracking under visually disorienting conditions. The first study showed that although vection and postural change are somewhat related to each other (for example, both were greater in response to roll and pitch as opposed to linear visual motion), the onset of vection is delayed by several seconds relative to the initiation of visually induced postural shifts. The second study showed that manual biases induced by visual roll motion are not overcome using a thumb-and-forefinger (pyramidal) motor strategy, and may not be equivalent to the "giant hand" illusion that is believed to reflect the predominance of the vestibulospinal (extrapyramidal) motor pathways during extreme spatial disorientation. These and other findings indicate that various visual orientation effects may involve at least partially independent mechanisms.

Humans

[Functional significance of 2 pathways of energy transport in cardiomyocytes].

To study the relative roles of creatine kinase (CK) and adenylate systems in cardiac energy turnover, the effect of CK inhibitor, iodoacetamide- (IAA, 0.5 mM), and 2-deoxyglucose-(DOG, 2 mM) induced) 65% depletion of adenine nucleotides at slightly decreased CK flux was determined in isolated rat heart. Both substances did not substantially affect contractile parameters of the isovolumic heart. However, an augmentation of cardiac work induced by isoproterenol addition was feeble and transient in IAA-treated hearts while the response of DOG-treated hearts was well preserved. The cardiac failure after IAA treatment was associated with irreversible fall in myocardial ATP content as evidenced by 31P-NMR technique. Furthermore, these hearts were unable to perform cardiac pump function due to insufficient cardiac filling and distensibility. The DOG-treated hearts exhibited 50% reduction in the pump function and were able to increase their work in elevated resistance. The results suggest that CK pathway is extremely important for both full cardiac relaxation and maximal contractile function.

Adenosine Triphosphate

Characteristics of local electrogram predicting successful transcatheter radiofrequency ablation of left-sided accessory pathways.

OBJECTIVES: The purpose of this study was to analyze and compare the local electrograms recorded at successful and unsuccessful sites of ablation to identify the criteria that may predict successful sites and minimize unnecessary radiofrequency delivery. BACKGROUND: Transcatheter ablation of accessory pathways using radiofrequency energy requires extremely precise localization of an accessory pathway. METHODS: Local electrograms from 50 consecutive patients with left-sided accessory pathways who underwent transcatheter radiofrequency ablation were analyzed. During catheter ablation, localization of accessory pathways was performed in 39 pathways during pre-excited sinus rhythm and in 14 pathways during orthodromic tachycardia. A total of 429 local electrograms at target sites obtained before delivery of radiofrequency current was analyzed. A prospective study was performed in another 20 patients using the criteria derived from the retrospective study. RESULTS: Accessory pathway conduction block was achieved in 36 (92%) of 39 pathways in which mapping was performed during pre-excited sinus rhythm and in 9 (64%) of 14 pathways in which mapping was performed during orthodromic tachycardia (p less than 0.05). When mapping was performed during pre-excited sinus rhythm, a combination of four variables (that is, an accessory pathway potential, stability of local electrograms, atrial activation greater than 1 mV and ventricular activation preceding the onset of the delta wave) showed a 62% probability of success. In contrast, excluding these variables resulted in a 95% probability of failure (noneffective or transiently effective). The prospective study shows that the use of these criteria can significantly reduce the number of current applications. When mapping was performed during orthodromic tachycardia, recording the earliest atrial activation was the most powerful predictor of success. A stable local electrogram with a small notch on the ventricular potential, presumed to be an accessory pathway potential, may add predictive value. CONCLUSIONS: Transcatheter radiofrequency ablation is highly effective in the treatment of patients with left-sided accessory pathways. Specific characteristics of local electrograms can be important predictors of success or failure. Mapping during pre-excited rhythm renders ablation more effective than does mapping during orthodromic tachycardia.

Adolescent

[Substitute pathways of the arterial system of the lower extremities].

Some ideas emphazied by RENARD and his collaborators were rediscovered.--Anastomosis doesnt always signify compensation and it is often difficult to appreciate the functional importance of the anastomoses shown by arteriographies.--The most valuable compensations are made by short ways. Long ways only come into action when the shorter are obliterated. Finally a certain number of arteries play an important role in the compensatory circulation, that is:--the system of lumbar arteries--the hypogastric artery--the origin of the deep femoral artery.

Arteries

Primulina pan-genome reveals differential gene retention following whole-genome duplications and provides insights into edaphic specialization.

Primulina, a genus of >200 species specialized to extreme soils, provides a model for edaphic adaptation. We assemble seven genomes and construct a pan-genome spanning nine species from karst, Danxia, and acidic soils. Comparative analyses reveal that karst-adapted species have smaller genomes. Two lineage-specific whole-genome duplications (WGDs) exhibit biased duplicate loss in large gene families but preferential retention of transcription factors, indicating combined adaptive and nonadaptive forces. Pan-genome analyses identify ion channel and transporter genes enriched in variant hotspots and under positive selection in karst lineages. Candidate genes for drought and salt stress tolerance include ABC transporters and ion channels. Notably, an ABC transporter shows positive selection in karst species and unique structural variation in non-karst species. Together, our findings show that genome downsizing, biased post-WGD retention, and evolution of ion-transport pathways shape adaptation to extreme soils. The Primulina pan-genome provides a resource for dissecting mechanisms underlying edaphic specialization.

Gene Duplication

De novo transcriptome assembly and gene expression analysis of Cnidium officinale under high-temperature conditions.

BACKGROUND: The medicinal plant Cnidium officinale (CO) is widespread in Northeast Asia and vulnerable to heat stress. The naturally occurring composition of pharmacological ingredients of CO results in overall physiological consequences; therefore, it is crucial to have a comprehensive understanding of metabolic response to ambient heat in terms of acclimation to estimate how much CO is exposed to threatening environmental conditions. RESULTS: Transcriptome analysis is critical for understanding the consequences of long-term physiological adaptation of CO to abiotic stress. However, transcriptome analysis on this species, particularly under prolonged stress conditions, has remained limited. We employed a temperature gradient tunnel (TGT) to subject CO to high-temperature exposure for four months, enabling us to observe the cumulative effects of heat and assess its acclimation mechanisms. In the absence of genome sequencing data, we performed de novo transcriptome assembly and compared DEGs from temperature treatment plots of a TGT and a growth chamber (GC). Since interpreting transcriptomic data can be complex, we employed a sequential analytical approach, including DEG clustering, GO enrichment, KEGG pathway mapping, miRNA-target gene analysis, and multiple rounds of RNA sequencing validation. DEGs were classified into two categories: genes exhibiting significant fold changes and genes showing significant count changes rather than fold changes. Then, we analyzed the functional roles of DEGs to determine which pathways respond to ambient and stressful high temperatures and validated the findings through cross-comparison with GC. Additionally, we conducted miRNA analysis to investigate post-transcriptional regulation under high temperatures. CO grown under higher ambient temperatures exhibited slight upregulation of pathways related to protein stability and turnover, ABA biosynthesis, and energy production, such as photosynthesis and oxidative phosphorylation. However, under extreme heat stress, most metabolic pathways were downregulated except for those involved in transcription, translation, oxidative phosphorylation and the biosynthesis of cutin, suberin, and wax. CONCLUSION: This study demonstrated that proper clustering of genes based on expression levels and fold changes in two different experimental conditions, along with pathway mapping, may provide a comprehensive understanding of CO's response to heat stress. These insights could contribute to future research on heat tolerance and crop improvement.

Gene Expression Profiling

[Background [corrected] activity and evoked responses of pigeon cerebellar cortex neurons to stimulation of the vagus nerve and nerves of the extremities].

Background activity and evoked responses of cortical cerebellar neurons to electrical stimulation of n. vagus and limb nerves were investigated in decerebrated pigeons. The neuronal responses were of tha same type independing of the type of stimulation. The phasic and tonic responses were chiefly of an excitatory type. The phasic responses were short (10-20 ms) and long-latent (up to 80 ms). The latter were predominant. The neuronal responses to n. vagus stimulation as compared with responses to limb nerves stimulation were observed in a smaller number of neurons and revealed longer latent periods and lower ability to rhythmic reproduction. They could not be produced through the climbing fibres.

Animals

Migration of a particulate radioactive tracer from the vagina to the peritoneal cavity and ovaries.

In this report we describe a radionuclide procedure designed to evaluate the migration of a particulate radioactive tracer from the vagina to the peritoneal cavity and ovaries, as well as the determination of the patency of the pathways between these two extremes of the female reproductive system. 99mTc-labelled human albumin microspheres (99mTc-HAM) were deposited in the posterior fornices of 24 patients a day before they were to undergo different gynaecological operations. During this period sequential images were obtained and after the operation radioactivity levels in the removed organs and tissues were counted with a scintillation detector. In 14 out of 21 cases, the ovaries and fallopian tubes were counted separately from the uterus. Nine were positive (radioactivity levels were sufficiently high in the tubes and ovaries) and 5 were negative (no substantial radioactivity levels could be detected in either the tubes or the ovaries). The 5 negative results all occurred in patients with proved tubal damage as a result of previous infection. All the results were either true positive or true negative, providing evidence of migration, or obstruction, of 99mTc-HAM from the vagina through the uterus and tubes to the peritoneal cavity and ovaries.

Adult

Postprandial rest pain and claudication of the lower extremity: A case report.

Postprandial rest pain and claudication in the lower extremities may occur in arteriosclerotic aortic occlusion when mesenteric and systemic collateral pathways provide inadequate blood flow to the extremity. The symptoms occur as a result of vasodilation of the distal mesenteric vascular bed with a concomitant increase in mesenteric blood flow which leads to a decrease in mesenteric artery to extremity collateral blood flow. This normal physiologic phenomenon, increase in mesenteric blood flow, causes the extremity pain. Such symptoms indicate a quite significant decrease in blood flow to the extremity, and prompt surgical correction is indicated. Aortofemoral reconstruction yields total reflief of the symptom complex.

Aortic Diseases

A study on the pathogenesis of postmastectomy lymphedema.

In order to study the causes of postmastectomy lymphedema, venography, lymphangiography and RISA absorption test were performed on the patients following radical mastectomy. Venous obstruction was a rare cause of postmastectomy lymphedema. Edema patterns in arm lymphangiography were observed in the patients with lymphedema and even in some of the non-edematous upper extremities. The finding of axillary lymphangiography was correlated with the degree of edema of the upper extremity. The absence of adequate lymphatic pathway across the axilla (type 2, collateral and type 3, blocking) was thought to provide the pathologic base for the postmastectomy lymphedema. RISA absorption test also provided precise information of the lymphatic flow in the extremity. It was lower in the patients with edema, as compared with the patients without edema.

Arm

Utilization of adenosine for nucleotide synthesis in the erythrocytes of some animals.

Erythrocytes of human, monkey, dog, rat, mouse, guinea pig, hen, or frog were incubated with [U-14C]adenosine at a concentration of 0.23 muM, a level roughly corresponding to its plasma level in mammals. Direct utilization of adenosine by phosphorylation (the kinase pathway) and indirect utilization via hypoxanthine (the hypoxanthine pathway) were analyzed from the ratio of the specific radioactivities of nucleotide and base, as described previously (1,2). Both human and monkey cells efficiently utilized adenosine only by the kinase pathway, while rodent cells used the same route with an efficiency which varied with the species. Canine cells incorporated adenosine in extremely small amounts both by the kinase pathway and via the hypoxanthine pathway with a marked predominance of the former. Frog erythrocytes were similar to dog cells in mechanism of utilization, but the efficiency was of the same level as that of the primates. In contrast to other animals tested, the avian cells utilized twice as much adenosine via the hypoxanthine pathway as by the kinase pathway.

Adenosine

Subcutaneous and skeletal muscle vascular responses in human limbs to lower body negative pressure.

Cardiopulmonary baroreceptor unloading in humans comparably increases sympathetic discharge to skeletal muscle in the forearm and calf, but blood flow studies have disclosed differential rather than uniform vasomotor responses in the extremities. The aim of the present study was to address the issue of differential effects of orthostatic stress on forearm and calf vascular adjustment and to extend previous studies by determining changes in vascular responses separately in various vascular beds of the limbs. The local [133Xenon] washout method was used for recording blood flow rates in subcutaneous tissue and skeletal muscle. Simultaneous recordings from the forearm and calf were performed in 11 healthy young males during lower body negative pressure at -10 mmHg. Heart rate, arterial mean and pulse pressures did not change during lower body negative pressure. In the forearm blood flow rates decreased significantly, in subcutaneous tissue by 16 +/- 2% (mean +/- SEM) and in skeletal muscle by 16 +/- 1%. In the calf lower body negative pressure induced a significant decrease in blood flow rates of 17 +/- 3% in subcutaneous tissue and of 30 +/- 2% in skeletal muscle. This vasoconstriction in calf skeletal muscle was consistently disclosed in both legs and was about the same magnitude in each calf when studied with the one leg exposed to lower body negative pressure and the other outside the lower body negative pressure chamber. These findings suggest that during unloading of cardiopulmonary afferents, reflex sympathetic activation as an important autonomic adjustment to orthostatic stress is accompanied by uniform vasoconstriction in subcutaneous and skeletal muscle vascular beds of human limbs.

Adult