Age and gender differences in medicare expenditures and service utilization at the end of life for lung cancer decedents.
Gender and age differences in medical care are well documented. We examined age and gender differences in Medicare expenditures for lung cancer decedents in the last year of life (LYOL) through a cross-sectional study of Medicare administrative and claims data. Participants were aged Medicare beneficiaries (>or=68) with lung cancer, who were covered by Parts A and B for 36 months before death (1996-1999; n = 13,120). Regression techniques were used to estimate age and gender differences in mean Medicare utilization and expenditures in the LYOL overall and by type of service, conditional on use: inpatient, outpatient, physician, skilled nursing facility (SNF), home health, and hospice, controlling for demographic, clinical, geographic, and supply characteristics. Women were more likely than men to use inpatient, SNF, home health, and hospice services. Women's average expenditures were approximately dollars 1,900 greater than men's, with differences attributed to higher average expenditures for SNF, home health, and hospice. Older cohorts used fewer inpatient and outpatient services and used more SNF and hospice services in their LYOL. Average Medicare expenditures were significantly lower in older cohorts (dollars 8,487 less for those age >or=85 at death than for those 68-74). Adjusting for age explains most of the gender differences in average Medicare expenditures. Remaining gender differences vary across age cohorts, with larger gender differences in social-supportive service expenditures among those 68-74 and 75-84 and outpatient and physician services among those 75-84 and >or=85. Our findings suggest that gender disparities in expenditures are generally small at the end of life for lung cancer decedents, particularly among the older cohorts. As expected, the bigger observed differences are by age although the direction of the association is not consistent across types of service. Higher expenditures for women on social-supportive services may reflect fewer informal supports for older women compared with men.


31P NMR as a spectroscopic monitor of the spontaneous precipitation of calcium phosphates.
High-resolution 31P NMR spectroscopy is shown to be a potentially valuable new method for monitoring the spontaneous precipitation of calcium phosphates from metastable supersaturated solutions. An apparatus capable of pH-statting the sample in a spinning 20 mm NMR sample tube is briefly described. The spontaneous precipitation of dicalcium phosphate dihydrate, CaHPO4 X 2H2O, pH-statted at pH 5, is characterized by a base-uptake curve which follows the decrease in the intensity of the solution 31P resonance. The precipitation of amorphous calcium phosphate at neutral pH, which exhibited an induction period of approximately 10 min, was also studied. No evidence of NMR peaks from transient clusters or the initial colloidal solid phase has been seen.


Capturing advanced human cognitive abilities with deep neural networks.
How can artificial neural networks capture the advanced cognitive abilities of pioneering scientists? I suggest they must learn to exploit human-invented tools of thought and human-like ways of using them, and must engage in explicit goal-directed problem solving as exemplified in the activities of scientists and mathematicians and taught in advanced educational settings.


Genetic landscape of APOE in human longevity revealed by high-throughput sequencing.
Apolipoprotein E (APOE) gene has been the most replicated longevity-associated gene in humans. Two common APOE alleles are either significantly depleted (ε4 allele) or enriched (ε2 allele) in long-lived individuals as compared to controls. We performed high-throughput sequencing analysis of exons and 2kb proximal promoter of APOE in 450 centenarians and 500 controls of Ashkenazi Jewish decent. We found two common regulatory variants, rs405509 (p=0.006) and rs769449 (p=0.036), that were significantly depleted in centenarians. Genotyping analysis of rs7412 and rs429358 showed significant enrichment of ε2 allele (p=0.003) and ε2/ε3 genotype (p=0.005), and significant depletion of ε3/ε4 genotype (p=0.005) in centenarians. Our findings support the hypothesis that variants in both coding and regulatory regions of APOE may contribute to longevity in humans.


Partial sequencing of two forms of concanavalin A-unbound collagenase inhibitor from bovine gingiva.
Three forms of collagenase inhibitor, one ConA-bound and two ConA-unbound, were extensively purified from bovine gingiva by sequential column chromatography. Analysis by sodium dodecyl sulphate-polyacrylamide gel electrophoresis revealed that inhibitory activity resides in proteins with M(r) of 26000-28000 and 22000 for ConA-bound and two ConA-unbound inhibitors, respectively. Of these, two ConA-unbound inhibitors were partially sequenced in the first 12 amino acids and found to have an identical sequence. The NH2-terminal sequence had 100% identity with TIMP-2 or MI.


Identifying tumor patients' depression.
The aim of this study was to compare the precision of two different methods in detecting clinical depression in tumor patients: the use of a screening questionnaire versus the assessment by health care providers (nurses and doctors). During their first days of inpatient cancer treatment, tumor patients were interviewed using the Structured Clinical Interview for DSM (SCID). Their physicians and nurses were asked to assess the mental health of the patients and their need for professional psychosocial support. Additionally, every patient completed the Hospital Anxiety and Depression Scale (HADS). Out of 329 patients, 28 were diagnosed with either a major or a minor depression according to the SCID. Physicians assessed 15 of the depressed patients as being depressed (sensitivity, 0.54; specificity, 0.38). Nurses identified 19 (sensitivity, 0.68; specificity, 0.45) and the HADS 27 (sensitivity, 0.96; specificity, 0.50) of the depressed patients. The HADS performed well in detecting depressed cancer patients in acute oncological care, whereas physicians and nurses often were unable to recognize depressed patients.


The relationship between GAD65 autoantibody and the risk of T1DM onset.
Type 1 diabetes mellitus (T1DM) is a well-known autoimmune disease, characterized by β-cell destruction in pancreas islet cells, which results insulin deficiency and subsequent hyperglycemic sequelae. While there is screening for type 2 DM that leads to better glycemic control and outcome, the majority of T1DM patients are diagnosed when much of the pancreatic cells and their function are disturbed. The aim of this article is to present an overview of the effective factors in the positivity of Glutamic acid decarboxylase antibody )GADA( and identifying the high-risk individuals for T1DM. We searched English literature available at National Library of Medicine via PubMed, and Google Scholar through December 2020. Finally, 79 papers have been included in the study. Studies were summarized based on the number of positive autoantibodies and onset of T1DM over time and GADA correlation with different variables. GADA is an easy marker to measure that can be detected many months prior to the clinical presentation and remains positive even after early childhood.


Do flushed biodegradable wet wipes really degrade?
Consumer wet wipes sold as biodegradable and flushable have tripled in market size in the last decade (>$3 billion in 2022), spurred by concerns over their potential harmful impact. Whilst predominantly composed of cellulosic fibres such as cotton, rayon, or wood pulp, these have been found to persist in sewers and in the environment in near equal abundance to their 'synthetic' counterparts. This questions whether flushed biodegradable wet wipes really degrade. Working from first principles, we therefore explore the physicochemical composition, environmental interactions, and degradation processes throughout the entire life cycle of cellulosic wet wipe fibres, from production to environmental fate, to understand their degradation behaviour in wastewater and freshwater systems. The results highlight that >50 % of biodegradable and flushable wipes are commonly manufactured with both biological biodegradable cellulose-based fibres and low-degradable synthetic fibres, and that they contain various property-enhancing chemical additives that can limit degradation. Whilst cellulose fibres in wet wipes are highly prone to physical fragmentation, their molecular degradation is difficult within the environment. This is due to the physicochemical manufacturing properties of wet wipes and the usually inadequate ambient conditions for its breakdown, creating persistent and possibly biologically harmful microfibres. We conclude that currently, most flushed biodegradable wet wipes do not really degrade, and that more empirical investigations are needed on their in-situ degradation behaviour and the environmental and manufacturing processes that may influence this breakdown. In doing so, full life cycle approaches to wet wipes should be adopted, considering their manufacturing properties, consumer disposal behaviour, and environmental implications.


Effects of diabetes mellitus on step length and minimum toe clearance adaptation.
Adaptive gait involves the ability to adjust the leading foot in response to the requirement of dynamic environments during walking. Accurate adjustments of the minimum toe clearance (MTC) height and step length can prevent older people from falling when walking and responding to hazards. Although older people with diabetes fall more frequently than healthy older adults, no previous studies have quantified their adaptive gait abilities. This study aimed to investigate the effects of diabetes mellitus on step length and MTC height adjustments using a non-immersive virtual-reality system. Sixteen young adults (26 ± 5 years, 7 females), 16 healthy older adults (68 ± 5 years, 6 females), and 16 older adults with diabetes (70 ± 5 years, 6 females) completed adaptability tests while walking on a treadmill. A computer system visualised a continuous real-time signal of absolute step length and MTC on a monitor. Each person responded to four discrete participant-specific step length and MTC visual targets that were presented on the same signal. Tasks were to match the peaks of interest on each signal to presented targets. Targets were 10% longer or shorter than the mean baseline step length, and 2.5 cm, and 3.5 cm higher than the mean baseline MTC. When a target was displayed, it remained unchanged for 10 consecutive foot displacement adaptation attempts. Then, the target was removed and a new target or the same target was present after 10 consecutive steps and remained for 10 steps. Each target was randomly presented three times (3 × 10). Step length and MTC height adjustments in response to targets were measured and compared among groups. Mean preferred walking speeds were not different among groups significantly when no targets were presented on the monitor in baseline walking. However, when participants walked on a treadmill while attempting to match step lengths or MTC heights to displayed targets on the monitor, the group with diabetes had reduced step length and MTC adjustments compared with other groups significantly. They showed greater errors (differences between their step lengths/MTC heights and presented targets) on the monitor. This study quantified reduced abilities for older individuals with diabetes to adjust both step length and MTC in response to stimuli compared to healthy older counterparts. Reduced step length and MTC height adjustments can increase falls in at risk populations. The presented virtual-reality system has merits for assessing and training step and MTC adaptation.


High expression of HOXA5 is associated with poor prognosis in acute myeloid leukemia.
HOXA5 is considered as an oncogene in many tumors. This study in- vestigated the HOXA5 expression in Chinese acute myeloid leukemia (AML) patients and evaluated the predictive significance of HOXA5 with a single-center retrospective study. We investigated the expression pattern and prognostic value of HOXA5 in patients with AML through by using a series of databases and various datasets, including the ONCOMINE, TCGA, and STRING datasets. The bone marrow samples of 53 newly diagnosed AML patients (non-M3 subtype) and 19 benign individuals were collected in our center. HOXA5 mRNA expression levels were detected by real-time qPCR, HOXA5 protein expression levels were detected by Western Blot. Clinical data was obtained from inpatient medical records. Two microarrays in Oncomine showed that the expression level of HOXA5 was significantly upregulated in AML. Our data revealed that AML patients had higher HOXA5 mRNA and protein expression levels than the controls (P < 0.001). The blast percentage in bone marrow of HOXA5 high-expression group was higher that of HOXA5 low-expression group (P < 0.05). Higher expression level of HOXA5 revealed a worse OS in AML (P < 0.05). Our findings suggested that HOXA5 might have the potential ability to act as a diagnostic biomarker and potential therapeutic target for AML.


Correction of diabetic pattern of insulin release from islets of the spiny mouse (Acomys cahirinus) by glucose priming in vitro.
Insulin release kinetics were studied in perifused islets of Langerhans, isolated from mildly hyperglycaemic and from normoglycaemic spiny mice (Acomys cahirinus), a rodent predisposed to develop spontaneously non-ketotic diabetes. In both groups, insulin response to glucose (16.7 mmol/l) was delayed in comparison with that of rat islets, the release kinetics being analogous to that of human Type 2 (non-insulin-dependent) diabetes. Thirty min priming of the isolated Acomys islets with glucose (16.7 mmol/l) resulted in potentiation of the insulin release to a second stimulation. The degree of potentiation decreased exponentially with the time interval between stimulations, showing a t1/2 of 18 min. Induction of potentiation by glucose was time-dependent, giving a maximal effect after 20 min of priming. In addition to overall amplification of the insulin response, priming with glucose accelerated markedly the initial release rates, correcting the dynamics of the response. We conclude that: (1) decreased and delayed insulin secretion is found in Acomys cahirinus before the development of hyperglycaemia; (2) induction of time-dependent potentiation in the islet by priming with glucose corrects the diabetic-type dynamics of insulin release; (3) therefore the deficient insulin release of Acomys is of a functional nature, the mechanism of potentiation bypassing the defect; (4) since insulin release in Acomys resembles that in prediabetic and diabetic man, similar conclusions might apply to the islet dysfunction in Type 2 diabetes.


Opposed phase imaging in lumbar disc disease: an option providing faster image acquisition times.
To investigate the utility of opposed phase imaging (OPI) (in-phase and out-of-phase) in lumbar disc disease. A total of 127 patients suspected of disc disease were examined with both traditional lumbar spine protocol (fast spin-echo [FSE] T1-weighted, T2-weighted sagittal, and T2-weighted axial) and OPI. Images were evaluated to detect the disc disease and to assess the anatomical clarity of certain spinal structures by two different radiologists using a four-point scale (1 = inadequate, 2 = adequate, 3 = good, and 4 = optimal). Results of two methods in terms of pathologic conditions and anatomical structures were compared. Comparison of the methods and the interpretations of two radiologists were performed by using kappa statistics. The difference among two methods in terms of anatomic clarity was assessed by using Wilcoxon analysis. Disc disease detected by each technique demonstrated concurrence (agreement was 82.4% and 93.1% for two radiologists; P < 0.05). OPI received similar scores with conventional sequences for disc disease (P > 0.05). OPI was optimal in displaying disc, marrow, osteophytes, and hemangiomas, where other structures got higher scores on conventional images (P > 0.05 and P > 0.001). But these structures had equal scores at least in one of the opposed-phase images. Acquisition time for OPI and conventional images were 4.46 and 9.01 minutes, respectively. OPI can be a faster backup technique in evaluating the lumbar disc disease. It has a shorter image acquisition time with adequate diagnostic quality. It can be a "time saver" option for busy MR centers or may be used for patients who cannot tolerate longer acquisition times.


Radiation tolerance of normal temporal bone structures: implications for gamma knife stereotactic radiosurgery.
Popular current thought states that hearing loss and facial weakness after radiosurgery of vestibular schwannomas is a function of cranial nerve damage. Although this may be true in some cases, the middle and inner ear contain rich networks of other sensitive structures that are at risk after radiotherapy and that may contribute to toxicity afterward. We reviewed the limited reported data regarding radiation tolerance of external, middle, and inner ear structures, and perspectives for therapy with gamma knife stereotactic radiosurgery are addressed.


Monascus-fermented metabolite monascin suppresses inflammation via PPAR-γ regulation and JNK inactivation in THP-1 monocytes.
Fermentation products of the fungus Monascus offer valuable therapeutic benefits and have been used extensively for centuries in Asia. The aim of this study is to investigate the inhibitory effect of the Monascus-fermented metabolite monascin (MS) on the molecular mechanism of ovalbumin (OVA)-induced inflammation in the human THP-1 monocyte cell line. We found that 1, 5, and 25 μM of MS significantly attenuated several proinflammatory mediators, including inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression as well as nitric oxide (NO) and prostaglandin E(2) (PGE(2)) formation caused by OVA stimulation. Further, 5 and 25 μM of MS significantly reduced the generation of tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6) at both the protein and mRNA levels. MS (5 and 25 μM) decreased OVA-induced phosphorylation of mitogen-activated protein kinase (MAPK) c-Jun NH(2)-terminal kinase (JNK), but not that of extracellular signal-regulated kinase (ERK) or p38 kinase. We used the peroxisome proliferator activated receptor-γ (PPAR-γ) antagonist GW9662 to show that MS inhibit JNK phosphorylation through increased expression of PPAR-γ. Thus, the metabolites from Monascus fermentation may serve as a dietary source of anti-inflammatory agents.


Early detection of COPD in general practice: implementation, workload and socioeconomic status. A mixed methods observational study.
Chronic obstructive pulmonary disease (COPD) is underdiagnosed in general practice. Our aim was to implement a population-based approach for the early detection of COPD and to assess its impact on primary care workload and costs, and the influence of socioeconomic status (SES). An observational study with mixed methods was performed in 10 Dutch general practices of either low or moderate to high SES. The Respiratory Health Screening Questionnaire was posted during a three-month period to all persons aged 45, 55, and 65 years (one age group per month). The practices calculated the risk, and patients at high risk of COPD were invited for spirometry at the practice. The general practitioner used the spirometric results and a consultation to establish a clinical diagnosis. Qualitative and quantitative data on workload, cost, and barriers were evaluated. Ten practices returned 293 (35.3%) COPD risk tests for the three age groups. Participants from low SES practices responded better than those from moderate to high SES practices (40.8% vs. 30.5%). In practices with low SES 17.9% of the tests indicated high risk compared with 16.1% in practices with moderate to high SES. Nine patients (23%) were newly diagnosed with COPD. The healthcare providers' extra workload averaged 18.5 hours during the three months for one standard practice. The average cost of this survey programme (three age groups in three months) was €520 for low SES practices and €398 for moderate to high SES practices. All healthcare providers affirmed that the extra workload in this survey model is acceptable and feasible when finances are compensated. Early detection of COPD is feasible in daily life primary care. In moderate to high SES practices the costs of detecting COPD were less than in low SES practices.


Comparison of image quality of corneal and retinal optical coherence tomography using sedation and general anesthesia protocols with or without retrobulbar anesthesia in horses.
To compare image quality and acquisition time of corneal and retinal spectral domain optical coherence tomography (SD-OCT) under 3 different sedation-anesthesia conditions in horses. 6 middle-aged geldings free of ocular disease. 1 randomly selected eye of each horse was evaluated via SD-OCT under the following 3 conditions: standing sedation without retrobulbar anesthetic block (RB), standing sedation with RB, and general anesthesia with RB. Five regions of interest were evaluated in the cornea (axial and 12, 3, 6, and 9 o'clock positions) and fundus (optic nerve head). Three diagnostic scans of predetermined quality were obtained per anatomical region. Image acquisition times and total scans per site were recorded. Corneal and retinal SD-OCT image quality was graded on a subjective scale from 0 (nondiagnostic) to 4 (excellent). Mean values for the standing sedation without RB, standing sedation with RB, and general anesthesia conditions were 24, 23, and 17, respectively, for total cornea scan attempts; 23, 19, and 19 for total retina-scan attempts; 14.6, 13.2, and 9.2 minutes for total cornea scan time; 19.1, 9.2, and 13.0 for total retina scan time; 2.0, 2.3, and 2.5 for cornea grade; and 2.7, 2.9, and 2.5 for retina grade. The RB facilitated globe akinesia and improved the percentage of scans in frame and region of interest accuracy for retinal imaging via OCT in horses. Retrobulbar blocks improved clinical image acquisition while minimizing motion artifact.


Timely withdrawal of G-CSF reduces the occurrence of thrombocytopenia during dose-dense chemotherapy.
Post chemotherapy Granulocyte colony stimulating factor (G-CSF) reduces leucopenia, while G-CSF priming shortly before chemotherapy increases myelotoxicity. We performed a trial with a two-schedule crossover design to determine the optimal G-CSF schedule for densified 2-weekly chemotherapy. During 2-weekly chemotherapy days 1 and 2, G-CSF was given on days 3-10, with a G-CSF-free interval before the next chemotherapy cycle of 5 days, or on days 3-13, with a G-CSF-free interval of 2 days. In schedule A, cycle II was preceded by a 5 days, cycle III and IV by a 2 days and cycle V by a 5 days G-CSF free interval. In schedule B, this was 2, 5, 5, and 2 days, respectively. Intra-patient comparison for cycles II versus III and cycles IV versus V showed that platelet (PLT) nadir count was significantly lower for cycles preceded by a 2-days compared to a 5-days G-CSF free interval: mean difference 45.7 x 10(9)/l (95% CI 33.2-58.2, p = 0.0001). Neutrophil count did not differ significantly (p = 0.85). Timely withdrawal of G-CSF in dose-dense chemotherapy reduces chemotherapy-related thrombocytopenia. Leucopenia was not aggravated, reflecting a protective effect of post-chemotherapy G-CSF.


Synchronous electrical stimulation of laryngeal muscles: an alternative for enhancing recovery of unilateral recurrent laryngeal nerve paralysis.
Although electrical stimulation of the larynx has been widely studied for treating voice disorders, its effectiveness has not been assessed under safety and comfortable conditions. This article describes design, theoretical issues, and preliminary evaluation of an innovative system for transdermal electrical stimulation of the larynx. The proposed design includes synchronization of electrical stimuli with laryngeal neuromuscular activity. To study whether synchronous electrical stimulation of the larynx could be helpful for improving voice quality in patients with dysphonia due to unilateral recurrent laryngeal nerve paralysis (URLNP). A 3-year prospective study was carried out at the Instituto Nacional de Rehabilitacion in the Mexico City. Ten patients were subjected to transdermal current electrical stimulation synchronized with the fundamental frequency of the vibration of the vocal folds during phonation. The stimulation was triggered during the phase of maximum glottal occlusion. A complete acoustic voice analysis was performed before and after the period of electrical stimulation. Acoustic analysis revealed significant improvements in all parameters after the stimulation period. Transdermal synchronous electrical stimulation of vocal folds seems to be a safe and reliable procedure for enhancing voice quality in patients with (URLNP).


Arthroscopic all inside repair of the lateral meniscus root tear.
It has been reported that lateral meniscus tears, including posterior horn tears, stable radial flap tears, or peripheral or posterior third tears that are combined with an Anterior Cruciate Ligament (ACL) injury can be treated with being left in situ. However, our experience has shown that the tear patterns are not so simple. They can show complex configurations and the inner side can be lost in chronic cases. Regarding the repair technique, there has been some controversy concerning the follow up results with repair devices and reduction is difficult using these devices if the inner side is non-viable or lost. If the tear involves whole width of bony insertion, it is believed that the meniscal function would be lost, particularly because the anatomic configuration is different in this area. In cases of chronic inner loss types, the meniscus was repaired using a side to side repair or pull out repair technique. Complete healing was achieved using this technique in some patients. Conclusively, Posterior Lateral Meniscus Root Tear (PLMRT) must be managed with different method with tears of other areas because the tear configuration is complex than simple looking.


Characterization of urine-derived cells from upper urinary tract in patients with bladder cancer.
To investigate whether cells isolated from the upper urinary tract (UTCs) possess stem cell characteristics and could be an alternative cell source for patients with bladder cancer. Current tissue engineering approaches for urologic tissue regeneration require invasive tissue biopsies to obtain autologous cells, and these procedures are associated with potential complications, such as donor site morbidity. Recently, cells isolated from voided urine (VUCs) have been proposed as an alternative cell source for urologic tissue engineering. However, VUCs should not be used in patients with bladder cancer, because the voided urine sample could contain malignant cells. Urine samples were collected from the upper urinary tract of 4 male patients with bladder cancer using a ureteral catheter. The samples were centrifuged and the pellets plated for primary culture. The cells were analyzed for colony-forming unit, proliferation rate, cytogenetics, stem cell characterization, and tumorigenicity. The results were compared with those of VUCs collected from 3 healthy men. The UTCs were able to form colonies, had a greater proliferation rate than the VUCs, and had a normal karyotype without any chromosomal aberrations. The UTCs possessed stem cell characteristics (expression of CD44+, CD73+, CD90+, CD105+, SSEA4+) and expressed several markers for urothelial, smooth muscle, and endothelial cell lineages. The UTCs did not form teratoma when implanted into the subcapsular space of a mouse kidney. The UTCs possessed stem cell characteristics and can potentially be an alternative cell source for urologic tissue regeneration in patients with bladder cancer.


A3 adenosine receptor agonist attenuates neuropathic pain by suppressing activation of microglia and convergence of nociceptive inputs in the spinal dorsal horn.
Peripheral nerve injuries cause glial activation and neuronal hyperactivity in the spinal dorsal horn. These changes have been considered to be involved in the underlying mechanisms for the development and maintenance of neuropathic pain. Using double immunofluorescence labeling, we previously demonstrated that spinal microglial activation induced by nerve injury enhanced convergence of nociceptive inputs in the spinal dorsal horn from uninjured afferents. The adenosine A3 receptor (A3AR) agonists have been shown to have antinociceptive activities in several experimental neuropathic pain models. However, the mechanisms underlying these antinociceptive actions of the A3AR agonist are still not fully explored. In this study, the effects of the A3AR agonist (i.e., IB-MECA) on microglial activation, enhancement of convergent nociceptive inputs, and nocifensive behaviors were examined after tibial nerve injury. Injury to the tibial nerve initially caused hyposensitivity to touch stimulus at 3 days, and then resulted in tactile allodynia at 14-day post-injury. The daily systemic administration of IB-MECA (0.1 mg/kg/day) for 8 days in a row starting on the day of nerve injury or 7 days after nerve injury prevented the development of behaviorally assessed hypersensitivities, and spinal microglial activation induced by nerve injury. These treatments also suppressed anomalous convergence of nociceptive primary inputs in the spinal dorsal horn. The present findings indicate that the A3AR agonist attenuates neuropathic pain states by suppressing enhanced microglial activation, and anomalous convergence of nociceptive inputs in the spinal dorsal horn from uninjured afferents after injury to the peripheral nerve.


[Usefulness of supplemental treatment with glypressin during the eradication phase of esophageal varices using endoscopic sclerotherapy].
The response of 20 patients with oesophageal varices randomly assigned to treatment by endoscopic sclerotherapy with or without adjuvant Glipressina was assessed on the basis of the following parameters: mean eradication time for oesophageal varices and frequency of bleeding during that period. The preliminary results suggest that the drug may have a favourable influence on both eradication time and bleeding in sclerotherapy.


A highly selective and sensitive ICT-based Cu2+ fluorescent probe and its application in bioimaging.
Cu2+ is an essential trace element for the organism, but its excess can also cause irreversible damage to the organism. As such, a "Turn-Off" fluorescent probe DPAP for the specific detection of Cu2+ was successfully constructed. DPAP exhibits large Stokes shift (120 nm), fast reaction speed (1 min), low detection limit (15.2 nM), low toxicity, and good cell permeability. Cu2+ quenches the fluorescence of DPAP by blocking its intramolecular charge transfer process to achieve the detection of Cu2+ and has been confirmed by HRMS, 1H NMR and DFT calculations. Excitingly, the five-cycle detection of Cu2+ and the successful recovery of trace Cu2+ in environmental water samples fully demonstrate the potential of DPAP for practical applications. In particular, DPAP can observe the distribution and translocation patterns of exogenous Cu2+ in HeLa cells and zebrafish in real-time. This research concept has offered important theoretical support for the study of the environmental behavior of heavy metal ions.


Long-term survival results of a randomized trial comparing gemcitabine plus cisplatin, with methotrexate, vinblastine, doxorubicin, plus cisplatin in patients with bladder cancer.
To compare long-term survival in patients with locally advanced or metastatic transitional cell carcinoma (TCC) of the urothelium treated with gemcitabine/cisplatin (GC) or methotrexate/vinblastine/doxorubicin/cisplatin (MVAC). Efficacy data from a large randomized phase III study of GC versus MVAC were updated. Time-to-event analyses were performed on the observed distributions of overall and progression-free survival. A total of 405 patients were randomly assigned: 203 to the GC arm and 202 to the MVAC arm. At the time of analysis, 347 patients had died (GC arm, 176 patients; MVAC arm, 171 patients). Overall survival was similar in both arms (hazard ratio [HR], 1.09; 95% CI, 0.88 to 1.34; P = .66) with a median survival of 14.0 months for GC and 15.2 months for MVAC. The 5-year overall survival rates were 13.0% and 15.3%, respectively (P = .53). The median progression-free survival was 7.7 months for GC and 8.3 months for MVAC, with an HR of 1.09. The 5-year progression-free survival rates were 9.8% and 11.3%, respectively (P = .63). Significant prognostic factors favoring overall survival included performance score (> 70), TNM staging (M0 v M1), low/normal alkaline phosphatase level, number of disease sites (<or= three), and the absence of visceral metastases. By adjusting for these prognostic factors, the HR was 0.99 for overall survival and 1.01 for progression-free survival. The 5-year overall survival rates for patients with and without visceral metastases were 6.8% and 20.9%, respectively. Long-term overall and progression-free survival after treatment with GC or MVAC are similar. These results strengthen the role of GC as a standard of care in patients with locally advanced or metastatic TCC.


Multimodality plaque ablation following failure of conventional wires and balloons to cross and to allow successful paclitaxel-eluting stent implantation of a chronic total occlusion.
Chronic total occlusion (CTO) is one of the most challenging coronary lesions to be faced in the catheterization laboratory. This report of a patient with stable angina and a CTO illustrates the potential problems that may arise and must be overcome, and demonstrates the utilization of technologies including the Intraluminal wire.


Lymph node content of supraclavicular and thoracodorsal-based axillary flaps for vascularized lymph node transfer.
Microvascular transfer of lymph node flaps has recently gained popularity as a treatment for secondary lymphedema often occurring after axillary, groin, or pelvic lymph node dissections. This study aimed to delineate the lymph node contents and pedicle characteristics of the supraclavicular (SC) and thoracodorsal (TD)-based axillary flaps as well as to compare lymph node quantification of surgeon vs pathologist. SC and TD flaps were dissected from fresh female cadavers. The surgeon assessed pedicle characteristics, lymph node content, and anatomy. A pathologist assessed all flaps for gross and microscopic lymph node contents. The κ statistic was used to compare surgeon and pathologist. Ten SC flaps and 10 TD flaps were harvested and quantified. In comparing the SC and TD flaps, there were no statistical differences between artery diameter (3.1 vs 3.2 mm; P = .75) and vein diameter (2.8 vs 3.5 mm; P = .24). The TD flap did have a significantly longer pedicle than the SC flap (4.2 vs 3.2 cm; P = .03). The TD flap was found to be significantly heavier than the SC flap (17.0 ± 4.8 vs 12.9 ± 3.3 g; P = .04). Gross lymph node quantity was similar in the SC and TD flaps (2.5 ± 1.7 vs 1.8 ± 1.2; P = .33). There was good agreement between the surgeon and pathologist in detecting gross lymph nodes in the flaps (SC κ = 0.87, TD κ = 0.61). The SC and TD flaps have similar lymph node quantity, but the SC flap has higher lymphatic density. A surgeon's estimation of lymph node quantity is reliable and has been verified in this study by comparison to a pathologist's examination.


The retinal choroid as an oculovascular biomarker for Alzheimer's dementia: A histopathological study in severe disease.
Previous in vivo optical coherence tomography studies have proposed the retinal choroid as a potential oculovascular biomarker for Alzheimer's disease (AD). However, the clinical use of the choroid as a purported surrogate marker remains poorly understood. We pursued a histopathological approach to assess choroidal thickness and vascular morphology in severe disease. Human postmortem tissues from 8 patients with AD (mean age: 80.1 ± 12.7 years) and from 11 age-matched controls (mean age: 78.4 ± 16.57 years) were analyzed. Thickness, area, and vascularity of the retinal choroid and its sublayers were measured from the nasal and temporal quadrants of the superior retina. Nasally, the choroid was thinner in the patients with AD than in the controls (22% thickness reduction; P < .001), but to our surprise, the choroid was thicker in the patients with AD than in the controls (~60% increase; P < .03) within the macula, temporally. The choroidal area was also significantly greater in the patients with AD than in the controls (~60% increase; P < .03). Choroidal thickening in AD was strongly correlated with the stromal vessel number (R2 = 0.96, P < .001). We found significant differences in the retinal choroid by layer and by region, nasally and temporally with respect to the optic nerve. Intriguingly, the choroid was markedly thicker in the central macular region and was strongly associated with vessel number in the stromal vascular layer. These quantified histological findings in severe disease expand our understanding of vascular pathology in AD and suggest vascularity as a potential biomarker supplementary to thickness when evaluating the retinal choroid in AD.


Murine monoclonal antibodies against Gerbich antigens.
Two murine monoclonal antibodies (E11-1 and MR4-130) agglutinated all samples of human red cells except those of the Ge (-1, -2, -3) phenotype. It was possible to demonstrate that these antibodies recognize two different epitopes of the Gerbich antigen.


Imposed load versus voluntary investment: Executive control and attention management in dual-task performance.
Dual task performance is one of the most frequently used paradigm in the evaluation of coping with concurrent task demands. The Breakfast Task experimented in this paper, was originally developed as a general indicator of coping ability with high demand executive control and attention management requirements. It is a computer-based simulation, in which the performer is required to cook several food items while concurrently setting table for guests. The task was employed in different studies, to compare young to old adults, monolinguals to bilinguals, influence of Parkinson disease and brain injury. However, in a closer examination, it is a dual task setting, in which cooking reflects coping with imposed load while table setting is an indicator of strategy free, voluntary invested effort. Models of workload did not examine the impact of such asymmetric flexibility on concurrent performance. Three experiments with elaborated versions of the breakfast task, show that the difference between the tasks affects concurrent performance formats in response to manipulations of task difficulty, priority change and practice. These results and their implications are discussed in reference to limited capacity, resource and executive control models of multitasking and task load.


Optimising the performance of frontline implementers engaged in the NTD programme in Nigeria: lessons for strengthening community health systems for universal health coverage.
The control and elimination of Neglected Tropical Diseases (NTDs) is dependent on mass administration of medicines (MAM) in communities and schools by community drug distributers (CDDs) who are supported and supervised by health facility staff (FLHF) and teachers. Understanding how to motivate, retain and optimise their performance is essential to ensure communities accept medicines. This study aimed to capture and translate knowledge, problems and solutions, identified by implementers, to enhance NTD programme delivery at the community level in Nigeria. Qualitative data was collected through participatory stakeholder workshops organised around two themes: (i) identification of problems and (ii) finding solutions. Eighteen problem-focused workshops and 20 solution-focussed workshops were held with FLHF, CDDs and teachers in 12 purposively selected local government areas (LGA) across two states in Nigeria, Ogun and Kaduna States. The problems and solutions identified by frontline implementers were organised into three broad themes: technical support, social support and incentives. Areas identified for technical support included training, supervision, human resource management and workload, equipment and resources and timing of MAM implementation. Social support needs were for more equitable drug distributor selection processes, effective community sensitisation mechanisms and being associated with the health system. Incentives identified were both non-financial and financial including receiving positive community feedback and recognition and monetary remuneration. The results led to the development of the 'NTD frontline implementer's framework' which was adapted from the Community Health Worker (CHW) Generic Logic Model by Naimoli et al. (Hum Resour Health 12:56, 2014). Maximising performance of frontline implementers is key to successful attainment of NTD goals and other health interventions. As NTDs are viewed as a 'litmus test' for universal health coverage, the lessons shared here could cut across programmes aiming to achieve equitable coverage. It is critical to strengthen the collaboration between health systems and communities so that together they can jointly provide the necessary support for frontline implementers to deliver health for all. This research presents additional evidence that involving frontline implementers in the planning and implementation of health interventions through regular feedback before, during and after implementation has the potential to strengthen health outcomes.


Evaluation of Glycan-Binding Specificity by Glycoconjugate Microarray with an Evanescent-Field Fluorescence Detection System.
Glycan microarray is an essential tool to study glycan-binding proteins called lectins. Using glycan microarrays, glycan-binding specificity can be analyzed by incubation with an array in which a series of glycans are immobilized. Various research groups in the world have developed glycan microarray. Among them, our glycan microarray has two unique points: one is the incorporation of the evanescent-field fluorescence detection system, and another is the use of multivalent glycopolymers. These two unique properties allow high-sensitive detection from a relatively limited amount of only nanograms of lectins, which could even be applied in crude samples such as cell lysates and cell culture media. Thus, this system is suitable for the first screening of lectins, lectin-like molecules, lectin candidates, and lectin mutants. Here we describe the protocols to analyze glycan-binding specificity of lectins using our glycan microarray system.


Age-related mortality in patients treated endoscopically for bleeding peptic ulcer.
Before the widespread use of endoscopic therapy, mortality from peptic ulcer hemorrhage was highest in elderly patients, and many deaths in this group were a consequence of postoperative complications. Endoscopic intervention greatly reduces the need for an emergency surgical operation, and consequently increasing age may no longer be a risk factor for death from bleeding ulcer. To examine this hypothesis, the outcome of 326 patients undergoing endoscopic therapy for bleeding peptic ulcer was related to age. One hundred two patients were less than 60 years of age (group I), 116 were 61 to 74 years of age (group II), and 108 were older than 75 years (group III). More group III patients were women (p < .0001) and were receiving nonsteroidal anti-inflammatory drugs (p < .0001). Associated concomitant diseases were significantly more common in group II and group III patients (p < .001). Forty-nine (45%) group III patients bled from gastric ulcers. More of group II patients were receiving anticoagulant drugs (p < .005). A previous history of peptic ulcer was most common in group I (p < .005), and duodenal ulcer was usually the cause of bleeding in this group. The three groups were well matched in terms of endoscopic stigmata (active bleeding and nonbleeding vessel), admission hemoglobin concentration, the presence of shock, and total transfusion requirements. Endoscopic therapy (injection or heater probe) was possible in 95% of all patients. The need for surgical intervention tended to be lowest in group I (11%, 19%, and 18%), whereas hospital mortality (3%, 6%, and 5%) was very similar. In this large group of unselected patients with major peptic ulcer bleeding, age did not significantly influence response to endoscopic therapy or hospital mortality.


Self-limiting, cell type-dependent replication of an integrase-defective human immunodeficiency virus type 1 in human primary macrophages but not T lymphocytes.
Integration of retroviral DNA into the host cell genome, catalyzed by the integrase (IN) protein, is thought to be required for replication. We show here that one IN-minus defective mutant of human immunodeficiency virus type 1 (HIV-1) is able to replicate in macrophages but not in peripheral blood lymphocytes (PBLs). Replication of the HIV-1 defective mutant, however, was inefficient and self-limiting. The absence of integration in the HIV-1 IN mutant in contrast to the wild-type implies that the replication of the IN mutant depends on the transcription of the extrachromosomal forms of viral DNA. In both PBLs and macrophages circular forms of DNA were detected at significant levels, indicating that the lack of a complete functional IN protein does not preclude nuclear import of HIV-1 DNA. Cell-associated p24 was absent in the IN-defective-infected PBLs, suggesting a transcriptional block of the extrachromosomal forms of HIV-1. These results show the existence of different strategies for HIV-1 replication depending upon the cell type, and indicate the necessity of integration of viral DNA for the self-maintained progression of the infection.


The heightened focus on wellness in dermatology residency education.
Dermatology residents and dermatology faculty members experience stress in the workplace, placing them at risk for burnout. As a profession, dermatologists have one of the fastest growing rates of burnout clinical manifestations across all specialties. The Accreditation Council for Graduate Medical Education has revised its program requirements for residency programs to include greater emphasis on actions to promote wellness. Examples of actions to promote wellness that are used currently in dermatology and other residency and medical education settings are explored.


A person-centered approach in studying coronavirus pandemic response: The role of HEXACO-PI-R and PANAS dimensions.
The main aim of this study was to explore reactions to the COVID-19 pandemic and their relationship with personality traits using a person-centered approach. Sample of 471 Serbian citizens was collected during the first 7 weeks of the pandemic. Cluster analysis revealed three clusters based on reactions to the pandemic: Adapted, Antagonized, and Passive. Adaptive type is characterized by stable emotional reactions and adherence to behavioral guidelines. Antagonized cluster is characterized by lowered adherence to behavioral guidelines, while Passive cluster is characterized by increased fear and boredom. Clusters differed significantly on HEXACO and PANAS traits. Similarity of obtained clusters with prototypes that commonly emerge using personality traits for classification, stresses the importance of basic individual differences in pandemic-induced behavior.


Oxytocin localization and function in the A1 noradrenergic cell group: ultrastructural and electrophysiological studies.
Antibodies to oxytocin and noradrenalin were utilized in an immunocytochemical study of the caudal ventrolateral medulla of the rat brainstem. Noradrenalin was visualized by using antibodies to noradrenalin and by means of a silver-gold intensification of diaminobenzidine, whereas oxytocin could be demonstrated in the same section by using the diaminobenzidine precipitate as a marker. At the light microscopic level, oxytocin fibers were densely distributed around the A1 cell bodies. At the ultrastructural level, oxytocin-containing fibers were seen to terminate synaptically onto noradrenalin-containing neurons. Previous studies have shown that electrical stimulation of A1 neurons selectively activates vasopressin-secreting neurons in the supraoptic nucleus. Therefore, separate electrophysiological studies were set up, in which we observed that oxytocin infusions (100-200 pg) into the A1 area enhanced the activity of 16 out of 19 putative vasopressin-secreting neurons and elicited no response from any of 10 oxytocin-secreting neurons. This finding suggests that some of the parvicellular neurons in the paraventricular nucleus of the hypothalamus, from which the A1 neurons derive their oxytocin innervation, can activate the A1 cell group via this peptidergic neurotransmitter. One of the consequences of A1 neuronal activation is enhanced firing of hypothalamic supraoptic (and paraventricular) vasopressin-secreting neurons, and a consequent rise in plasma vasopressin.


Immune evasion in Kaposi's sarcoma-associated herpes virus associated oncogenesis.
A hallmark of herpesviruses is a lifelong persistent infection, which often leads to diseases upon immune suppression of infected host. Kaposi's sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus 8 (HHV8), is etiologically linked to the development of Kaposi's sarcoma (KS), primary effusion lymphoma (PEL), and Multicentric Castleman's disease (MCD). In order to establish a persistent infection, KSHV dedicates a large portion of its genomic information to sabotage almost every aspect of host immune system. Thus, understanding the interplay between KSHV and the host immune system is important in not only unraveling the complexities of viral persistence and pathogenesis, but also discovering novel therapeutic targets. This review summarizes current knowledge of host immune evasion strategies of KSHV and their contributions to KSHV-associated diseases.


Microarray-based method to analyze methylation status of E-cadherin gene in leukemia.
Aberrant DNA methylation of the CpG sites of the tumor suppressor gene is closely associated with carcinogenesis. Recently, several studies have indicated the aberrant methylation of E-cadherin gene could be a potential marker for leukemic patients. We used bisulfite-modified DNA as a template for PCR amplification, resulting in conversion of unmethylated, but not methylated, cytosine into thymine within CpG islands of interest. The amplified product containing a pool of DNA fragments with altered nucleotide sequences was then hybridized with an oligonucleotide-based microarray. Five sets of oligonucleotide probes were designed to detect the methylation patterns of E-cadherin gene CpG islands in leukemia samples. The results were further validated by methylation-specific PCR (MSP). We found that all leukemia samples were methylated at different levels within the target sequences. The specific regions (the CpG sites #16-19 and #20-22) were revealed as hotspots for methylation in leukemic patients. These results showed that the microarray assay could successfully detect methylation changes of E-cadherin gene in leukemia quantitatively. The oligonucleotide-based microarray can be a quick and reliable tool to map methylation status in CpG islands. This established microarray could be potentially useful for clinical researches and diagnosis.


Men with acromegaly need higher doses of octreotide than women.
To investigate the effect of gender on the response of GH to short-acting octreotide in patients with acromegaly, and on the GH and IGF-1 levels during long-term treatment with a slow-release formulation of octreotide. Twenty-one men (mean age 54 years; range 26-78) and 15 women (mean age 54 years; range 22-74) with acromegaly were treated with subcutaneous injections of 100 microg short-acting octreotide twice daily. Serum samples for GH were taken before start of treatment, in the morning prior to the injection, and 1, 3, 5 and 7 h after the injection. Thirteen men (mean age 56 years; range 34-78) and 12 women (mean age 64 years; range 28-81) with acromegaly were switched from ongoing treatment with short-acting octreotide to injections of the slow-release formulation. A 4-h GH-profile and morning IGF-1 were taken at start and after 3, 9, 15 and 21 months of treatment. Subcutaneous injections of 100 microg octreotide reduced the mean level of GH during a 7-h period to a similar extent in men and women compared to the GH levels prior to the injections. During long-term treatment with similar doses of the depot formulation of octreotide, the mean IGF-1 level remained significantly higher in the men than in the women, whereas there were no differences in the mean GH levels between the two groups. The responses to short- and long-acting octreotide illustrate an effect of gender, due to different sensitivity to GH in the periphery. Furthermore, the results show that in the treatment of acromegaly, men will need higher doses of octreotide than women to normalize IGF-1.


Surgical management of the lens and retrolenticular fibrotic membranes associated with persistent fetal vasculature.
To evaluate a surgical technique that allows safe, effective, near-total removal of retrolenticular fibrotic membranes in eyes with persistent fetal vasculature syndrome (PFVS). Pediatric ophthalmologist's academic practice. This retrospective review comprised 5 children (6 eyes) who had excision of a retrolenticular fibrovascular membrane during cataract surgery over a 6-month period. Long, spoke-like radial incisions of the membrane were made to the ciliary processes, resulting in wedge-shaped segmentation of the membrane. A vitrector was used to excise each wedge and perform an anterior vitrectomy. The mean age at time of surgery was 8 months (range 1 to 24 months) and the mean follow-up, 9 months (range 2 to 13 months). The membrane was successfully removed in all eyes. One eye of a patient who did not comply with the postoperative medical regimen or follow-up developed pupillary block glaucoma requiring pupilloplasty and trabeculectomy. This anterior surgical technique to remove tenacious retrolenticular membranes associated with PFVS was effective, allowing near-total removal of the offending fibrovascular membrane.


A rare case of acute eosinophilic pneumonia induced by vaping-associated lung injury: a case report.
Acute eosinophilic pneumonia (AEP) is well-known as one of the primary eosinophilic pulmonary diseases of unknown etiology. It's defined as a febrile illness along with acute onset respiratory failure that is commonly misdiagnosed at the initial presentation as infectious pneumonia. Despite the fact that AEP sometimes classified as idiopathic as no exact cause can be identified in most cases, it has been suggested recently to be linked with electronic cigarette or vaping products and associated with electronic cigarette or vaping associated lung injury (EVALI). Therefore, history of recent tobacco smoking or vaping exposure along with peripheral eosinophilia are crucial clinical findings suggestive of AEP. A previously healthy 17-year-old female presented to the Emergency Room with one day history of progressively worsening shortness of breath accompanied by left sided pleuritic chest pain and fever. She wasn't taking any medications, denied traditional cigarette smoking, exposure to pulmonary irritants, recent travel and had no history of close contact with sick patient. She recently started vaping 20 days prior to the presentation. Initially, she was admitted with a presumptive diagnosis of atypical pneumonia but was found to have AEP due to a recent vaping exposure. Vaping is a well-known health hazard that has become a growing trend among adolescents and have been promoted as a safe and effective alternative to traditional cigarettes. The etiology of AEP remains unclear, but many studies suggest a possible link with recent tobacco smoking or vaping. A key challenge for this clinical entity is to reach the diagnosis after excluding all other pulmonary eosinophilia causes, and it has an excellent prognosis if diagnosed early and treated appropriately.


Exploring Communication Practices in Italian Physiotherapy: Knowledge and Use of Effective Communication Strategies-A National Descriptive Study.
This study aimed to investigate the knowledge and use of effective communication strategies among Italian physiotherapists. We utilized a questionnaire consisting of 19 questions to collect data on the knowledge and use of effective communication strategies among Italian physiotherapists. The results revealed that only 35.8% of the respondents reported being aware of communication strategies related to physiotherapy, with their first exposure occurring during their three-year degree. Despite the majority of respondents agreeing that communication is an effective strategy for improving patient adherence, only about half reported making moderate use of open-ended questions and metaphors during treatment sessions. Furthermore, more than half of the respondents reported being unaware of Motivational Interviewing. The results of this study found that there is a consensus among Italian physiotherapists about the importance of effective communication in clinical practice, though the knowledge and application of some communication strategies remain limited. These findings suggest that there is room for improvement in the training and education of physiotherapists in Italy, with a need for greater emphasis on communication strategies in the university educational curriculum, starting from the bachelor's degree.


Ecofriendly production of silver nanoparticles using Candida utilis and its mechanistic action against pathogenic microorganisms.
Silver nanoparticles (AgNPs) have attracted great interest due to their applications in various areas. In the present study ecofriendly biosynthesis of extracellular silver nanoparticles was carried out using Candida utilis NCIM 3469. Characterization of synthesized AgNPs was done by UV-visible spectroscopy, Scanning electron microscopy and antibacterial activity. AgNPs are found spherical in shape with size in the range of 20-80 nm. AgNPs showed antibacterial activity against pathogenic organisms such as Pseudomonas aeruginosa, Staphylococcus aureus, and Escherichia coli. The SEM analysis confirms the antibacterial activity of Ag nanoparticles due to damage of cytoplasmic membrane. AgNPs synthesized by C. utilis could be applicable in the development of antibacterial water filters for treatment of water.


Dosimetric parameters that predict late rectal complications after curative radiotherapy in patients with uterine cervical carcinoma.
Late rectal complication (LRC) was a major late complication in patients with uterine cervical carcinoma who were treated with a combination of external beam radiotherapy (EBRT) and high-dose-rate intracavitary irradiation (HDR-ICR). For the current study, the authors retrospectively evaluated dosimetric parameters that were correlated with LRC > or = Grade 2 in patients with uterine cervical carcinoma who were treated with curative radiotherapy, and they analyzed the appropriate dose estimates to the rectum that were predictive for LRC > or = Grade 2. Between July 1994 and September 2002, 157 patients who were diagnosed with Stage IB-IIIB cervical carcinoma and were treated with definitive radiotherapy were included. EBRT (41.4-66 grays [Gy] in 23-33 fractions) to the whole pelvis was delivered to all patients, with midline shielding performed after a 36-50.4 Gy external dose. HDR-ICR (21-39 Gy in 6-13 fractions to Point A) was administered at a rate of 2 fractions weekly after midline shielding of EBRT. LRC was scored using Radiation Therapy Oncology Group criteria. The total biologically effective dose (BED) at specific points, such as Point A (BED(Point A)), rectal point (BED(RP)), and maximal rectal point (BED(MP)), was determined by a summation of the EBRT and HDR-ICR components, in which the alpha/beta ratio was set to 3. Analyzed parameters included patient age, tumor size, stage, concurrent chemotherapy, ICR fraction size, RP ratio (dose at the rectal point according to the Point A dose), MP ratio (dose at the maximal rectal point according to the Point A dose), EBRT dose, BED(Point A), BED(RP), and BED(MP). The 5-year actuarial overall rate of LRC > or = Grade 2 in all patients was 18.4%. Univariate analysis showed that the RP ratio, MP ratio, EBRT dose, BED(Point A), BED(RP), and BED(MP) were correlated with LRC > or = Grade 2 (P < 0.05). Multivariate analysis showed that, of all clinical and dosimetric parameters evaluated, only BED(RP) was correlated with LRC > or = Grade 2 (P = 0.009). The 5-year actuarial rate of LRC > or = Grade 2 was 5.4% in patients with a BED(RP) < 125 Gy(3) and 36.1% in patients with a BED(RP) > or = 125 Gy(3) (P < 0.001). BED(RP) was a useful dosimetric parameter for predicting the risk of LRC > or = Grade 2 and should be limited to < 125 Gy(3) whenever possible to minimize the risk of LRC > or = Grade 2 in patients with uterine cervical carcinoma who are treated with a combination of EBRT and HDR-ICR. Cancer 2005.


Convenient one-pot synthesis of novel 2-substituted benzimidazoles, tetrahydrobenzimidazoles and imidazoles and evaluation of their in vitro antibacterial and antifungal activities.
A series of novel 2-substituted benzimidazoles and imidazoles have been synthesized from long-chain alkenoic acids. The reactions occurred under relatively mild conditions and afforded the desired product in good yields. The structures of these compounds have been elucidated by elemental and spectral (IR, (1)H NMR, (13)C NMR, mass) analyses. Furthermore, compounds were screened for in vitro antibacterial activity against the representative panel of two gram-positive and two gram-negative bacteria. All the synthesized compounds were also tested for their inhibitory action against five strains of fungus. The various compounds show potent inhibitory action against test organisms.


Rapid condylar degeneration after glenoid fossa prosthesis insertion: report of three cases.
Three cases of temporomandibular joint disc replacement with a polymer glenoid fossa prosthesis, followed by rapid condylar degeneration, are reported. The relationship between this degeneration and a consistent foreign body reaction to fragments caused by implant wear is postulated.


MR imaging of the female pelvis at 3 Tesla: evaluation of image homogeneity using different dielectric pads.
To evaluate improvements in image homogeneity in pelvic MR imaging at 3 Tesla (T) using two different dielectric pads. A total of eight healthy females were scanned using a 3T MR scanner equipped with a body-array coil. Axial and sagittal fast spin-echo T2-weighted images (T2WI) (TR/TE = 3200 msec/94 msec), axial fast spin-echo T1-weighted images (T1WI) (TR/TE = 700 msec/11 msec), and sagittal half-Fourier acquisition single-shot turbo spin-echo (HASTE) images (TR/TE = 3000 msec/100 msec) were performed for pelvic imaging. Sequences were repeated with dielectric pads (consisting of either ultrasound [US] gel or water), and without pads. Three or four regions of interest (ROIs) were placed on fatty tissues and the ratio of minimum to maximum signal intensity (RSI) was calculated as a marker of image homogeneity. RSI was significantly higher on T2WI and T1WI when using dielectric pads than when no pad was used. A similar tendency was observed in RSI on HASTE. No significant difference was found between images with US gel pads and those with water pads. Dielectric pads consisting of either US gel or water are effective in improving image homogeneity of the pelvis on 3T MRI.


The dark brown integumentary pigment of a barnacle (Balanus eburneus). A comparative study.
A histochemical analysis involving tinctorial and solubility tests was pursued in conjunction with electron microscopy for the purpose of identifying the dark brown epidermal pigment of a barnacle (Balanus eburneus) as melanin and/or ommochrome. Histochemically, comparisons were made with other brown pigments located in the subcarapal epidermis of another crustacean, the fiddler crab (Uca pugilator), the dorsal skin of the red-backed salamander (Plethodon cinereus), the liver and testis of a slider turtle (Chrysemys sp.) and the substantia nigra of human brain. The solubility properties of the pigment of the two crustacean invertebrates were in general similar to one another and markedly different from the pigment of the three vertebrates. Insolubility in appropriate solvents classified the vertebrate pigment as melanin. The invertebrate pigment, however, which was soluble in the ommochrome solvents, concentrated sulfuric and formic acids and 2-chloroethanol, remained insoluble in the ommochrome solvents, dilute aqueous and methanolic hydrochloric acid and dilute sulfuric acid. On the basis of these solubilities, an unequivocal classification of the invertebrate pigment as either melanin or ommochrome did not appear possible. The tinctorial and electron microscopic properties of the barnacle pigment were also equally ambiguous in regard to its specific classification.


Deploying Proteins as Electrolyte Additives in Li-S Batteries: The Multifunctional Role of Fibroin in Improving Cell Performance.
It is widely accepted that the commercial application of lithium-sulfur batteries is inhibited by their short cycle life, which is primarily caused by a combination of Li dendrite formation and active material loss due to polysulfide shuttling. Unfortunately, while numerous approaches to overcome these problems have been reported, most are unscalable and hence further hinder Li-S battery commercialization. Most approaches suggested also only tackle one of the primary mechanisms of cell degradation and failure. Here, we demonstrate that the use of a simple protein, fibroin, as an electrolyte additive can both prevent Li dendrite formation and minimize active material loss to enable high capacity and long cycle life (up to 500 cycles) in Li-S batteries, without inhibiting the rate performance of the cell. Through a combination of experiments and molecular dynamics (MD) simulations, it is demonstrated that the fibroin plays a dual role, both binding to polysulfides to hinder their transport from the cathode and passivating the Li anode to minimize dendrite nucleation and growth. Most importantly, as fibroin is inexpensive and can be simply introduced to the cell via the electrolyte, this work offers a route toward practical industrial applications of a viable Li-S battery system.


Carcinoma of the lip.
(1) Carcinoma of the lip occurs predominantly in men in their seventh and eighth decades of life. (2) Epidermoid carcinoma is the most common malignant lip tumor. (3) Metastases to cervical lymph nodes are uncommon. (4) Elective neck dissection is not indicated. (5) Therapeutic radical neck dissection can benefit the patient in the presence of proved suprahyoid lymph node metastases. (6) The five year survival rate for epidermoid carcinoma of the lip is higher than the rate for epidermoid carcinoma of other sites in the oral cavity or pharynx. (7) Local recurrence does not correlate with the size of the primary tumor. (8) Initial treatment failures can frequently be salvaged surgically.


Diet and its role in interstitial cystitis/bladder pain syndrome (IC/BPS) and comorbid conditions.
What's known on the subject? and What does the study add? Nearly 90% of patients with interstitial cystitis/bladder pain syndrome (IC/BPS) report sensitivities to a wide variety of dietary comestibles. Current questionnaire-based literature suggests that citrus fruits, tomatoes, vitamin C, artificial sweeteners, coffee, tea, carbonated and alcoholic beverages, and spicy foods tend to exacerbate symptoms, while calcium glycerophosphate and sodium bicarbonate tend to improve symptoms. At present we recommend employing a controlled method to determine dietary sensitivities, such as an elimination diet, in order to identify sensitivities while at the same time maintain optimal nutritional intake. We review current literature with regard to diet's effect upon IC/BPS and common comorbidities (irritable bowel syndrome, fibromyalgia, chronic fatigue syndrome, neuropathic pain, vulvodynia, and headache) with a focus upon questionnaire-based investigations. We discuss the pathologic mechanisms that may link diet and IC/BPS related-pain, concentrating upon specific comestibles such as acidic foods, foods high in potassium, caffeine, and alcohol. Up to 90% of patients with interstitial cystitis/bladder pain syndrome (IC/BPS) report sensitivities to a wide variety of comestibles. Pathological mechanisms suggested to be responsible for the relationship between dietary intake and symptom exacerbation include peripheral and/or central neural upregulation, bladder epithelial dysfunction, and organ 'cross-talk', amongst others. Current questionnaire-based data suggests that citrus fruits, tomatoes, vitamin C, artificial sweeteners, coffee, tea, carbonated and alcoholic beverages, and spicy foods tend to exacerbate symptoms, while calcium glycerophosphate and sodium bicarbonate tend to improve symptoms. Specific comestible sensitivities varied between patients and may have been influenced by comorbid conditions. This suggests that a controlled method to determine dietary sensitivities, such as an elimination diet, may play an important role in patient management.


Pulmonary mechanics in normal infants and young children during first 5 years of life.
To characterize lung function in young children we measured lung compliance and pulmonary conductance in 40 normal infants and children ranging in age from the newborn period to 5 years. Inspiratory and expiratory flow was measured by a pneumotachograph, esophageal pressure through a water-filled feeding tube, and functional residual capacity (FRC) by a N2 washout technique. The esophageal pressure change per breath [(mean +/- SD) 7.3 +/- 1.4 cm H2O] and specific compliance (75 +/- 13 ml/cm H2O/L-FRC) did not change with growth. Specific conductance was high (0.60 L/s/cm H2O/L-FRC) in preterm infants, decreasing rapidly with initial growth but minimally beyond 10 kg of body weight, and stabilizing at 0.10 L/s/cm H2O/L-FRC. During the age period studied, compliance increased approximately x 25 whereas conductance only rose five-fold. The changes in compliance and conductance were well correlated to FRC, body weight, and length. These findings suggest that in the last trimester of pregnancy the airways are already well developed and postnatal lung growth occurs mainly by formation of new alveoli, leading to a proportional increase in FRC and lung compliance. Postnatally, conductance increases much more slowly than FRC, resulting in a rapid drop in specific conductance.


Lung metastasectomy in adenoid cystic carcinoma (ACC) of salivary gland.
To define the role of surgical management of lung metastases in ACC. Twenty ACC patients referred to lung metastasectomy were retrospectively reviewed. Twenty-six operations were performed; at the first metastasectomy, a resection with clear margins (R0) was achieved in 11 patients (55%), 3 are alive and well. Four out of 9 patients with residual disease (R2) are still alive. Median survival after metastasectomy was 78 and 52 months for R0 and R2 (p=0.4); median freedom from progression (FFP) in R0 and R2 groups was 30 and 15 months (p=0.2), respectively. A better outcome was obtained for patients with a disease-free interval 36 months and 6 metastases and bilateral involvement were critical in achieving a R0 intervention. Lung metastasectomy provided a prolonged FFP in a high selected subset of patients with ACC. However, if this could be translated into a survival benefit, it is still to be demonstrated.


Monoenergetic neutrino beam for long-baseline experiments.
In an electron capture process by a nucleus, emitted neutrinos are monoenergetic. By making use of this, we study how to get a completely monoenergetic neutrino beam in a long-baseline experiment.


[Feasibility and preliminary experiment of a routine use of Da-VinciS in fertility surgery].
The goal of our study is to evaluate the use of Da-Vinci S in the field of fertility laparoscopic surgery. Ten successive patients were included for a laparoscopic fertility surgery using the Da-Vinci S. Surgical feasibility, operating time, length of hospital stay and postoperative complications have been analyzed. All procedures have been completed using Da-Vinci S. In our preliminary surgical experience, the Da-Vinci S can be technically used in the field of fertility surgery.


Post-operative adhesions after digestive surgery: their incidence and prevention: review of the literature.
Post-operative adhesions after gastrointestinal surgery are responsible for significant morbidity and constitute an important public health problem. The aim of this study was to review the surgical literature to determine the incidence, consequences and the variety of possible countermeasures to prevent adhesion formation. A systematic review of English and French language surgical literature published between 1995 and 2009 was performed using the keywords "adhesion" and "surgery". Peritoneal adhesions are reported as the cause of 32% of acute intestinal obstruction and 65-75% of all small bowel obstructions. It is estimated that peritoneal adhesions develop after 93-100% of upper abdominal laparotomies and after 67-93% of lower abdominal laparotomies. Nevertheless, only 15-18% of these adhesions require surgical re-intervention. The need for re-intervention for adhesion-related complications varies depending on the initial type of surgery, the postoperative course and the type of incision. The laparoscopic approach appears to decrease the risk of adhesion formation by 45% and the need for adhesion-related re-intervention to 0.8% after appendectomy and to 2.5% after colorectal surgery. At the present time, only one product consisting of hyaluronic acid applied to a layer of carboxymethylcellulose (Seprafilm(®)) has been shown to significantly reduce the incidence of postoperative adhesion formation; but this product is also associated with a significant increase in the incidence of anastomotic leakage when the membrane is applied in direct contact with the anastomosis. The use of this product has not been shown to decrease the risk of re-intervention for bowel obstruction. The prevention of postoperative adhesions is an important public health goal, particularly in light of the frequency of this complication. The routine use of anti-adhesion products is not recommended given the lack of studies with a high level of evidence concerning their efficacy and safety of use.


Adenosine stimulation of fluid transport across rabbit corneal endothelium.
The rate of fluid transport across rabbit corneal endothelium has been measured with an automatic volumetric method. The present resolution of the procedure is 1-3 nanoliters, and intervals of measurement can be made as small as seconds. In the presence of glucose, oxidized glutathione (GSSG), and adenosine, the maximal rates were 6.2+/-1.0 microliter/hr cm2, and 8.2+/-0.8 microliter/hr cm2 if a large portion of the stroma was dissected away. In the presence of glucose and GSSG only, the rates were lower, namely 3.7+/-0.5 microliter/hr cm2. The rates consistently increased or decreased when adenosine was added or deleted, respectively, during given experiments. The stimulation of fluid transport by adenosine was in the order of 40-50%. The results raise the possibility that this transport mechanism might be subject to metabolic control.


Three-dimensional color Doppler sonography and uterine artery arteriography of fibroids: assessment of changes in vascularity before and after embolization.
To assess the accuracy of three-dimensional color Doppler sonography and uterine artery arteriography in depicting changes in fibroid vascularity before and after embolization. Preembolization and postembolization three-dimensional color Doppler sonography and selective uterine artery arteriography were retrospectively compared in 15 patients who underwent uterine artery embolization for treatment of symptomatic fibroids. Three-dimensional color Doppler sonography was performed by using a scanner with color power angiographic imaging capability. Vascularity was quantified by using an estimation of power-weighted pixel density as described by our group in previously published studies. Uterine artery arteriography was performed by using a standard selective microcatheter embolization technique. For purposes of comparison, fibroids were classified as either hypervascular or hypovascular relative to myometrial vascularity before and minutes to several hours after uterine artery embolization. Changes in fibroid vascularity (i.e., from hypervascular to hypovascular) as depicted by three-dimensional color Doppler sonography were compared with those shown on uterine artery arteriography and classified as being in agreement or disagreement. In 13 (87%) of 15 patients there was agreement; in 2 (13%) of 15 there was disagreement. In both cases of disagreement, three-dimensional color Doppler sonography showed collateral flow not depicted by uterine artery arteriography The mean reduction in quantitated vascularity after uterine artery embolization was 44% (range, 19%-78%). Three-dimensional color Doppler sonography accurately depicts fibroid vascularity and in some cases can reveal collateral flow not depicted by uterine artery arteriography.


Lack of adrenomedullin, but not complement factor H, results in larger infarct size and more extensive brain damage in a focal ischemia model.
Adrenomedullin (AM) and its binding protein, complement factor H (FH), are expressed throughout the brain. In this study we used a brain-specific conditional knockout for AM and a complete knockout for FH to investigate the effect of these molecules on the pathophysiology of stroke. Following 48 h of middle cerebral artery permanent occlusion, there was a statistically significant infarct size increase in animals lacking AM when compared to their wild type littermates. In contrast, lack of FH did not affect infarct volume. To investigate some of the mechanisms by which lack of AM may augment brain damage, markers of nitrosative stress, apoptosis, and autophagy were studied at the mRNA and protein levels. There was a significant increase of inducible nitric oxide synthase (iNOS), matrix metalloproteinase-9 (MMP9), fractin, and Beclin-1 in the peri-infarct area of AM-deficient mice when compared to their wild type counterparts and to contralateral and sham-operated controls. These data suggest that AM exerts a neuroprotective action in the brain and that this protection may be mediated by regulation of iNOS, matrix metalloproteases, and inflammatory mediators. In the future, substances that increase AM actions in the central nervous system may be used as potential neuroprotective agents in stroke.


Incident Colorectal Cancer in Inflammatory Bowel Disease.
Colorectal cancer (CRC) risk is increased in Inflammatory Bowel Disease (IBD) and surveillance needs to be tailored according to individual risk. The open issues include the role of the characteristics of IBD and CRC in determining the long-term outcome. These issues were assessed in our multicenter study, including a cohort of 56 IBD patients with incident CRC. The clinical and histopathological features of IBD patients and of CRC were recorded. Incident CRC in IBD occurred at a young age (≤40 years) in 25% of patients (median age 55.5 (22-76)). Mucinous signet-ring carcinoma was detected in 6 out of the 56 (10.7%) patients, including 4 with Ulcerative Colitis (UC) and 2 with Crohn's disease (CD). CRC was more frequently diagnosed by colonoscopy in UC (85.4% vs. 50%; p = 0.01) and by imaging in Crohn's Disease CD (5.8% vs. 31.8%; p = 0.02). At onset, CRC-related symptoms occurred in 29 (51.9%) IBD patients. The time interval from the diagnosis of IBD to CRC was shorter in UC and CD patients with >40 years (p = 0.002; p = 0.01). CRC-related death occurred in 10 (29.4%) UC and in 6 (27.2%) CD patients (p = 0.89), with a short time interval from CRC to death (UC vs. CD: 6.5 (1-68) vs. 14.5 (8-40); p = 0.85; IBD: 12 months (1-68)). CRC occurring at a young age, a short time interval from the diagnosis of IBD to CRC-related death in the elderly, CRC-symptoms often mimicking IBD relapse and the observed high mortality rate may support the need of closer surveillance intervals in subgroups of patients.


Atrial Fibrillation Ablation: Do We Really Need Preprocedural Imaging?
Atrial fibrillation is the most common human arrhythmia, causing significant mortality and morbidity. Because of the potential for complications, it is important that procedures be made as safe and effective as possible by combining safe procedural planning with effective therapy delivery. To change the current approach, large randomized studies are needed to guide the selection of patients who may safely undergo ablation without transesophageal echocardiography to exclude thrombus. For institutions routinely using computed tomography and magnetic resonance imaging to assess pulmonary vein anatomy before procedures, the possibility of excluding intracardiac thrombi using these imaging modalities should be considered.


New prostaglandin synthetase inhibitors--di-and triphenylacrylonitriles.
16 triphenylacrylonitriles (TPE) or diphenylacrylonitriles (DPE) were synthesized by condensation of various benzophenones or benzaldehydes with various phenylacetonitriles. The pharmacological potency of these compounds was studied by incubation of bovine seminal vesicle microsomes and PG-RIA. The results showed that the potency of inhibition of PG biosynthetase of DPE was stronger than that of TPE. Compounds with electron-releasing functional groups were proved to be more effective than those with electron-attracting groups. Compound DPE-9 was the most active one, the potency of which was 40 times stronger than that of naproxen. The structure of some compounds has been analysed by X-ray diffraction. The relationship between structure and activity was investigated by means of X-ray diffraction, UV and NMR.


Efficacy and safety of intravenous combined with aerosolised polymyxin versus intravenous polymyxin alone in the treatment of multidrug-resistant gram-negative bacterial pneumonia: A systematic review and meta-analysis.
Previous studies have questioned the efficacy and safety of intravenous combined with aerosolised (IV + AS) polymyxin versus intravenous (IV) polymyxin alone in the treatment of patients with multidrug-resistant gram-negative bacterial (MDR-GNB) pneumonia. Therefore, we conducted a meta-analysis to evaluate the efficacy and safety of IV + AS polymyxin in the treatment of MDR-GNB pneumonia. We identified all relevant studies by searching the PubMed, EMBASE and Cochrane library databases from their inception to May 31, 2022. All included studies were evaluated using the Newcastle Ottawa scale (NOS) checklist. The summary relative risk (RR) and 95% confidence interval (CI) were used to determine the outcome differences between the IV + AS and the IV groups. Subgroup analysis was performed based on population, polymyxin dose and kinds of polymyxin. A total of 16 studies were included in the meta-analysis. The IV + AS group had lower mortality (RR = 0.86, 95% CI: 0.77-0.97, P = 0.01) than the IV group. Subgroup analysis revealed that IV + AS polymyxin could reduce mortality only when used in low doses. Simultaneously, the IV + AS group outperformed the IV group in terms of clinical response rate, clinical cure rate, microbiological eradication and duration of mechanical ventilation. The duration of hospitalisation and the incidence of nephrotoxicity did not differ significantly between the two groups. IV + AS polymyxin is beneficial in the treatment of MDR-GNB pneumonia. It could lower patient mortality and improve clinical and microbial outcomes without increasing the risk of nephrotoxicity. However, retrospective analysis in the majority of studies and heterogeneity between studies implies that our findings must be interpreted carefully.


Discovery of Teleost Plasma Kallikrein/Coagulation Factor XI-Like Gene from Channel Catfish (Ictalurus punctatus) and the Evidence that the Protein Encoded by it Acts as a Lectin.
Mammalian plasma kallikrein (PK) and coagulation factor XI (fXI) are serine proteases that play in the kinin-kallikrein cascade and in the blood clotting pathway. These proteases share sequence homology and have four apple domains (APDs) and a serine protease domain (SPD) from their N-terminus to C-terminus. No homologs of these proteases are believed to be present in fish species, except for lobe-finned fish. Fish, however, have a unique lectin, named kalliklectin (KL), which is composed of APDs only. In the present study, we found genomic sequences encoding a protein with both APDs and SPD in a few cartilaginous and bony fishes, including the channel catfish Ictalurus punctatus, using bioinformatic analysis. Furthermore, we purified two ~ 70 kDa proteins from the blood plasma of the catfish using mannose-affinity and gel filtration chromatography sequentially. Using de novo sequencing with quadrupole time-of-flight tandem mass spectrometry, several internal amino acid sequences in these proteins were mapped onto possible PK/fXI-like sequences that are thought to be splicing variants. Exploration of APD-containing proteins in the hagfish genome database and phylogenetic analysis suggested that the PK/fXI-like gene originated from hepatocyte growth factor, and that the gene was acquired in a common ancestor of jawed fish. Synteny analysis provided evidence for chromosomal translocation around the PK/fXI-like locus that occurred in the common ancestor of holosteans and teleosts after separation from the lobe-finned fish lineage, or gene duplication into two chromosomes, followed by independent gene losses. This is the first identification of PK/fXI-like proteins in teleosts.


The history of the United States Food, Drug and Cosmetic Act and the development of medicine.
The future role of pharmacologists in the evaluation of drugs will increase as scientific knowledge and our understanding of drugs and disease processes increase. In addition, political issues and public fears will place further demands on the scientific community to try to influence the drug regulatory process. The FDA continually issues directives which guide all phases of drug development, from the identification of a chemical as being of potential interest on therapy, through all animal tests and clinical phases (4).


Respiratory syncytial virus pneumonia in an adult renal transplant patient: an unexpected nosocomial infection.
This article describes a case of respiratory syncytial virus pneumonia believed to have been acquired nosocomially in an adult renal transplant recipient. The mode of transmission, diagnosis, and prevention of infection due to this virus in the immunocompromised patient are discussed.


Multiple particle tracking (MPT) using PEGylated nanoparticles reveals heterogeneity within murine lymph nodes and between lymph nodes at different locations.
Lymph nodes (LNs) are highly structured lymphoid organs that compartmentalize B and T cells in the outer cortex and inner paracortex, respectively, and are supported by a collagen-rich reticular network. Tissue material properties like viscoelasticity and diffusion of materials within extracellular spaces and their implications on cellular behavior and therapeutic delivery have been a recent topic of investigation. Here, we developed a nanoparticle system to investigate the rheological properties, including pore size and viscoelasticity, through multiple particle tracking (MPT) combined with LN slice cultures. Dense coatings with polyethylene glycol (PEG) allow nanoparticles to diffuse within the LN extracellular spaces. Despite differences in function in B and T cell zones, we found that extracellular tissue properties and mesh spacing do not change significantly in the cortex and paracortex, though nanoparticle diffusion was slightly reduced in B cell zones. Interestingly, our data suggest that LN pore sizes are smaller than the previously predicted 10-20 μm, with pore sizes ranging from 500 nm-1.5 μm. Our studies also confirm that LNs exhibit viscoelastic properties, with an initial solid-like response followed by stress-relaxation at higher frequencies. Finally, we found that nanoparticle diffusion is dependent on LN location, with nanoparticles in skin draining LNs exhibiting a higher diffusion coefficient and pore size compared to mesenteric LNs. Our data shed new light onto LN interstitial tissue properties, pore size, and define surface chemistry parameters required for nanoparticles to diffuse within LN interstitium. Our studies also provide both a tool for studying LN interstitium and developing design criteria for nanoparticles targeting LN interstitial spaces.


Long-term correction of murine glycogen storage disease type Ia by recombinant adeno-associated virus-1-mediated gene transfer.
Glycogen storage disease type Ia (GSD-Ia) is caused by a deficiency in glucose-6-phosphatase-alpha (G6Pase-alpha), a nine-transmembrane domain, endoplasmic reticulum-associated protein expressed primarily in the liver and kidney. Previously, we showed that infusion of an adeno-associated virus (AAV) serotype 2 vector carrying murine G6Pase-alpha (AAV2-G6Pase-alpha) into neonatal GSD-Ia mice failed to sustain their life beyond weaning. We now show that neonatal infusion of GSD-Ia mice with an AAV serotype 1-G6Pase-alpha (AAV1-G6Pase-alpha) or AAV serotype 8-G6Pase-alpha (AAV8-G6Pase-alpha) results in hepatic expression of the G6Pase-alpha transgene and markedly improves the survival of the mice. However, only AAV1-G6Pase-alpha can achieve significant renal transgene expression. A more effective strategy, in which a neonatal AAV1-G6Pase-alpha infusion is followed by a second infusion at age one week, provides sustained expression of a complete, functional, G6Pase-alpha system in both the liver and kidney and corrects the metabolic abnormalities in GSD-Ia mice for the 57 week length of the study. This effective use of gene therapy to correct metabolic imbalances and disease progression in GSD-Ia mice holds promise for the future of gene therapy in humans.


Charlson comorbidity index as a predictor of long-term outcome after surgery for nonsmall cell lung cancer.
To evaluate the impact of the Charlson comorbidity index on long-term survival in nonsmall cell lung cancer surgery and determine whether this index is a better predictor of long-term survival than individual comorbid conditions. From January 1989 to December 2001, 433 (340 men, 93 women) consecutive curative resections for nonsmall cell lung cancer were performed. Each patient was preoperatively assessed according to the Charlson comorbidity index. Survival curves were estimated by the Kaplan-Meier method. Risk factors for overall and disease free survival were determined by univariate and multivariate Cox regression analysis. The patients ranged in age from 37 to 82 years, with a mean age of 65 years. Hospital mortality was 3.7%. Five-year overall and disease free survival was 45 and 43%, respectively. Among patients with Charlson comorbidity grade 0, 5-year overall survival was 52%, among patients with Charlson comorbidity grade 1-2 it was 48%, and among patients with Charlson comorbidity grade > or =3 it was 28%. Univariate analysis showed that male gender, age, congestive heart failure, chronic pulmonary disease, Charlson comorbidity index, clinical stage, pathological stage, and type of resection were significantly associated with an impaired survival. Multivariate analysis showed that age (relative risk, 1.02; 95% confidence interval, 1.01-1.03), Charlson comorbidity grade 1-2 (relative risk, 1.4; 95% confidence interval, 1.0-1.8), Charlson comorbidity grade > or =3 (relative risk, 2.2; 95% confidence interval, 1.5-3.1), bilobectomy (relative risk, 1.7; 95% confidence interval, 1.2-2.5), pneumonectomy (relative risk, 1.5; 95% confidence interval, 1.1-2.0), pathological stage IB (relative risk, 1.5; 95% confidence interval, 1.1-2.2), IIB (relative risk, 1.9; 95% confidence interval, 1.2-3.0), IIIA (relative risk, 1.9; 95% confidence interval, 1.1-3.1), IIIB (relative risk, 2.8; 95% confidence interval, 1.2-6.8), and IV (relative risk, 12.4; 95% confidence interval, 3.2-48.2), were associated with an impaired survival. The Charlson comorbidity index is a better predictor of survival than individual comorbid conditions in nonsmall cell lung cancer surgery. We recommend the use of a validated comorbidity index in the selection of patients for NSCLC surgery.


Application of solid-state NMR restraint potentials in membrane protein modeling.
We have developed a set of orientational restraint potentials for solid-state NMR observables including (15)N chemical shift and (15)N-(1)H dipolar coupling. Torsion angle molecular dynamics simulations with available experimental (15)N chemical shift and (15)N-(1)H dipolar coupling as target values have been performed to determine orientational information of four membrane proteins and to model the structures of some of these systems in oligomer states. The results suggest that incorporation of the orientational restraint potentials into molecular dynamics provides an efficient means to the determination of structures that optimally satisfy the experimental observables without an extensive geometrical search.


Parental Care: When the Sex Has to Stop.
How is sexual conflict during reproduction resolved when parents collaborate to rear offspring? A new study shows that female burying beetles communicate their hormonal status to their male partners to avoid costly superfluous mating, using an anti-aphrodisiac pheromone.


Anesthetic management in a spinal cord-injured parturient woman with a left hip resection and secondary scoliosis: A case report.
Pregnancy after spinal cord injury, hip resection, leg amputation, and scoliosis is an uncommon event. Given the specific pathophysiological changes in this patient, an aesthetic management presented a particular challenge. The effects on the physiological changes associated with pregnancy, aesthetic methods, blood loss, autotransfusion from uterine contractions and thrombotic risk had to be considered. A 25-year-old female earthquake survivor was admitted at 36.4 weeks of pregnancy for preterm labor. She had suffered from a spinal cord injury and complex trauma and had subsequently undergone left hip resection, bilateral amputations, and multiple surgical procedures during the previous 6 years. Additionally, she had developed severe scoliosis due to her weight-bearing posture. High amputation after earthquake injury; Scoliosis; Vulvar reconstruction; Intrauterine pregnancy (35.6 weeks) with a single live fetus with possible premature delivery. We administered general anesthesia during a cesarean section for the parturient woman. Both the central venous pressure and pleth variability index were used to continuously evaluate intraoperative fluid management and blood loss. Delivery and patient recovery were uneventful. Anesthetic management of a pregnant woman with a spinal injury, scoliosis, left total leg and right below-knee amputations, and left hip resection requires considerable attention. Advances in medical technology have provided clinicians with insights into managing patients with this condition.


Correction to: The changing face of dental practice: emerging models of team care in Australia.
Author's correction note: Research article Br Dent J 2020; 228: 767-772.When this article was published there were errors in Figures 1 and 2. The correct version of and are presented here:The original article has been corrected.


C-kit signaling promotes proliferation and invasion of colorectal mucinous adenocarcinoma in a murine model.
It was reported that the receptor tyrosine kinase (RTK) family often highly expressed in several mucinous carcinomas. In the present study, we established a murine model of colorectal mucinous adenocardinoma (CRMAC) by treating C57 mice [both wild type (WT) and loss-of-function c-kit mutant type (Wads-/-)] with AOM+DSS for 37 weeks and found that c-kit, a member of RTK family, clearly enhanced the tumor cell proliferation by decreasing p53 and increasing cyclin D1 through AKT pathway. Significantly, c-kit strongly promoted tumor cell invasiveness by increasing ETV4, which induced MMP7 expression and epithelial-mesenchymal transition (EMT) via ERK pathway. In vitro up- or down-regulating c-kit activation in human colorectal cancer HCT-116 cells further consolidated these results. In conclusion, our data suggested that the c-kit signaling obviously promoted proliferation and invasion of CRMAC. Therefore, targeting the c-kit signaling and its downstream molecules might provide the potential strategies for treatment of patients suffering from CRMAC in the future.


Inferring functional miRNA-mRNA regulatory modules in epithelial-mesenchymal transition with a probabilistic topic model.
MicroRNAs (miRNAs) play important roles in gene regulatory networks. In this paper, we propose a probabilistic topic model to infer regulatory networks of miRNAs and their target mRNAs for specific biological conditions at the post-transcriptional level, so-called functional miRNA-mRNA regulatory modules (FMRMs). The probabilistic model used in this paper can effectively capture the relationship between miRNAs and mRNAs in specific cellular conditions. Furthermore, the proposed method identifies negatively and positively correlated miRNA-mRNA pairs which are associated with epithelial, mesenchymal, and other condition in EMT (epithelial-mesenchymal transition) data set, respectively. Results on EMT data sets show that the inferred FMRMs can potentially construct the biological chain of 'miRNA→mRNA→condition' at the post-transcriptional level.