A randomized comparison of the value of additional stenting after optimal balloon angioplasty for long coronary lesions: final results of the additional value of NIR stents for treatment of long coronary lesions (ADVANCE) study.
We sought to investigate the clinical benefit of additional stent implantation after achieving an optimal result of balloon angioplasty (BA) in long coronary lesions (>20 mm). Long coronary lesions are associated with increased early complications and late restenosis after BA. Stenting improves the early outcome, but stent restenosis is also related to both lesion length and stent length. A total of 437 patients with a single native lesion 20 to 50 mm in length were included and underwent BA, using long balloons matched to lesion length and vessel diameter (balloon/artery ratio 1.1) to achieve a diameter stenosis (DS) <30% by on-line quantitative coronary angiography (QCA). "Bail-out stenting" was performed for flow-limiting dissections or >50% DS. Patients in whom an optimal BA result was achieved were randomized to additional stenting (using NIR stents) or no stenting. The primary end point was freedom from major adverse cardiac events (MACE) at nine months, and core laboratory QCA was performed on serial angiograms. Bailout stenting was necessary in 149 patients (34%) and was associated with a significantly increased risk of peri-procedural infarction (p < 0.02). Among the 288 randomized patients, the mean lesion length was 27+/-9 mm, and the vessel diameter was 2.78+/-0.52 mm. The procedural success rate was 90% for the 143 patients assigned to BA alone (control group), as compared with 93% in the 145 patients assigned to additional stenting (stent group), which resulted in a superior early minimal lumen diameter (0.54 mm, p < 0.001) and led to reduced angiographic restenosis (27% vs. 42%, p = 0.022). Freedom from MACE at nine months was 77% in both groups. A strategy of provisional stenting for long coronary lesions led to bailout stenting in one-third of patients, with a threefold increase in peri-procedural infarction. Additional stenting yielded a lower angiographic restenosis rate, but no reduction in MACE at nine months.


Improving FTIR imaging speciation of organic compound residues or their degradation products in wall painting samples, by introducing a new thin section preparation strategy based on cyclododecane pre-treatment.
Fourier transform infrared (FTIR) imaging in transmission mode, employing a bidimensional focal plane array (FPA) detector, was applied for the detection and spatially resolved chemical characterisation of organic compounds or their degradation products within the stratigraphy of a critical group of fragments, originating from prehistoric and roman wall paintings, containing a very low concentration of subsisted organic matter or its alteration products. Past analyses using attenuated total reflection (ATR) or reflection FTIR on polished cross sections failed to provide any evidence of any organic material assignable as binding medium of the original painting. In order to improve the method's performance, in the present study, a new method of sample preparation in thin section was developed. The procedure is based on the use of cyclododecane C12H24 as embedding material and a subsequent double-side polishing of the specimen. Such procedure provides samples to be studied in FTIR transmission mode without losing the information on the spatial distribution of the detected materials in the paint stratigraphy. For comparison purposes, the same samples were also studied after opening their stratigraphy with a diamond anvil cell. Both preparation techniques offered high-quality chemical imaging of the decay products of an organic substance, giving clues to the painting technique. In addition, the thin sections resulting from the cyclododecane pre-treatment offered more layer-specific data, as the layer thickness and order remained unaffected, whereas the samples resulting from compression within the diamond cell were slightly deformed; however, since thinner and more homogenous, they provided higher spectral quality in terms of S/N ratio. In summary, the present study illustrates the appropriateness of FTIR imaging in transmission mode associated with a new thin section preparation strategy to detect and localise very low-concentrated organic matter subjected to deterioration processes, when the application of FTIR in reflection mode or FTIR-ATR fails to give any relevant information.


Effect of gender and estrous cycle on the pharmacokinetics of ethanol in the rat brain.
Aspects of ethanol pharmacokinetics in the blood, such as elimination, are known to vary by gender in the rat. Ethanol concentrations reaching the brain, which are relevant in affecting behavior, have not been measured rigorously by gender. This study used quantitative microdialysis to measure ethanol pharmacokinetics in the nucleus accumbens after a moderate dose of ethanol, comparing males with females and females across the estrous cycle. We administered 1 g/kg ethanol intravenously or intragastrically to male and female rats. We measured ethanol concentrations in the nucleus accumbens by use of microdialysis with in vivo probe calibration and compared them with concentrations in jugular venous blood. After intravenous delivery, apparent ethanol elimination was approximately 15% faster in females than males from both brain and blood. After intragastric delivery, blood ethanol concentrations peaked faster in females than males by approximately 20 min, suggesting faster absorption or diffusion from the stomach. Likewise, accumbal ethanol concentrations peaked faster in females than males by approximately 25 min, indicating faster distribution to the brain. These pharmacokinetic parameters did not vary across the estrous cycle, nor were they influenced significantly by body water. This study provides the first quantitative measurement of ethanol concentrations and, thus, pharmacokinetics in the brain of awake rats. If ethanol distribution to the brain varies between genders, as these results suggest, then differences in the pharmacological response to ethanol can be expected, providing a rationale for studying the pharmacodynamics of ethanol in the brain of the self-administering rat.


Life course linkages between enriching early-life activities and later life cognition: Evidence from the Wisconsin Longitudinal Study.
Prior research suggests that participation in enriching early-life activities (EELAs) has long-term benefits for cognitive health and aging. This study aims to examine the life course processes underlying these associations by drawing on theoretical models from life course epidemiology. Specifically, we tested sensitive-period effects, social pathways, and selection effects as potential explanations for linkages between greater participation in EELAs and better later life cognition. We drew on data from the Wisconsin Longitudinal Study (WLS), which is among the longest-running cohort studies in the U.S. that has followed graduates (all identified as non-Hispanic White) from Wisconsin high schools since 1957. We used prospective measures of key variables, including information from high school yearbooks, with assessments of cognitive performance at ages 65 and 72. Results from multilevel modeling indicated that greater participation in cognitively oriented extracurricular activities (but not physically nor socially oriented activities) was associated with both better language/executive functioning and memory at age 65. Although the size of these associations was reduced when accounting for other cognitive resources in adolescence (childhood socioeconomic status and adolescent cognitive ability) and in midlife (adult socioeconomic status and formal group participation), there remained small, yet statistically robust, associations. We did not find robust associations between greater EELA engagement and slower rates of decline in cognition between ages 65 and 72, nor did we find evidence of gender differences. Results suggest that for this cohort of older adults, EELA participation is part of life course "protective chains," whereby exposures to assets at one point in the life course increase the likelihood of subsequent exposures, each sequentially and in their own right, toward better later life cognition. We discuss how results support the importance of policies and practices to promote healthy cognitive development among youth for the long-term cognitive health of a rapidly aging U.S. population.


Training Surgical Residents to Communicate with Their Patients: A Scoping Review of the Literature.
Effective communication is critical in surgical practice and the Accreditation Council on Graduate Medical Education requires a focus on interpersonal and communication skills. Absent a national communication skills curriculum for surgical residents, individual programs have designed and implemented their own curricula. This scoping review explores communication training in North American surgical residency programs. The review was conducted according to PRISMA guidelines, and included articles identified through searches of 6 publication databases conducted on June 25, 2019 and updated on April 2, 2020. Eligible studies described patient or family communication skills education for surgical residents in North America. Published abstracts were excluded. Article abstracts were screened by 2 reviewers. For articles meeting criteria, data on study setting, participants, curriculum design, educational techniques, and skills focus were extracted and analyzed. A total of 2724 articles were identified after removing duplicates; 84 articles were reviewed in full text. Thirty-three met study criteria including 4 from 2006 to 2009 and 29 after 2010. The most common skills education focused on breaking bad news, followed by a range of topics, such as empathy, end of life and/or palliative care discussions, medical error disclosure, shared decision making, and informed consent. Some of the training was part of larger curriculum including team training or professionalism. Over half of the studies involved general surgery learners. The most common form of education included didactics followed by practice with peers or simulated patients. Only half of the programs described curricula involving multiple training sessions which is important for ongoing development and skill reinforcement. Effective communication skills are important, necessary, and increasingly incorporated into surgical training programs. While the literature is expanding, few surgical residency programs have described communication curricula. This review serves as a guide for programs interested in developing their own communication curricula for surgical residents.


Feeding responses of adapted and non-adapted insects to the defensive properties of Baccharis halimifolia L. (Compositae).
Trirhabda bacharidis (Weber) (Chrysomelidae), a univoltine, monophagous beetle is the dominant herbivore on Baccharis halimifolia (Compositae), a woody, perennial shrub that leafs out in early spring and retains its leaves into November. Available plant biomass increases during the season but T. bacharidis feeds only during spring and early summer. During the remainder of the growing season, there are no major herbivores feeding on B. halimifolia. B. halimifolia leaves increase in toughness and thickness and decrease in moisture and nutrients as the season progresses. In feeding preference tests, T. bacharidis larvae preferred young leaves over leaves of older age classes. When reared on leaves of different ages, larvae fed on young leaves, weighed more, pupated earlier and had greater survivorship. T. bacharidis larvae showed no significant feeding preference for similarly tough B. halimifolia leaves painted with differing concentrations of late season acetone leaf extract. Elm leaves painted with the same leaf extracts were avoided by larvae of the non-adapted specialist Pyrrhalta luteola (Mueller) (Chrysomelidae).These results suggest that the adapted specialist, T. bacharidis, is not deterred by the B. halimifolia acetone soluble secondary chemical which increases in amount over the season. Decreasing leaf nitrogen (perhaps in concert with increasing leaf toughness) seems to be the primary factor that dissuades its feeding. However, acetone soluble secondary chemicals in the leaves of B. halimifolia may be effective in preventing herbivory from non-adapted insects.


Functional polymorphisms of Monocyte Chemoattractant Protein-1 gene and Pott's disease risk.
Monocyte Chemoattractant Protein-1 (MCP-1/CCL2), a key player in immune-mediated responses against Mycobacterium tuberculosis, is encoded by a polymorphic gene. Functionally relevant polymorphic variations in the MCP-1 gene have been associated with both susceptibility to and protection against tuberculosis-related disorders. Here, we investigated the potential impact of some of these polymorphisms on Pott's disease risk in a patient cohort from Algeria. DNA from 132 Algerian patients with exclusive Pott's disease and 204 healthy controls, included under a case-control design, were analyzed for the MCP1 -2518A/G (rs1024611), -362G/C (rs2857656) and int1del554-567 (rs3917887) polymorphisms. PHASE software was used for haplotype reconstruction. Genetic associations were examined using chi-square tests. We found that the rs1024611 -2518 GG, rs2857656 -362 CC and rs3917887 int1del554-567 del/del homozygous genotypes each were significantly more prevalent in patients than in controls (respective corrected p value [Pc]=0.01, 0.04 and 0.04) Haplotype distribution profile further confirmed this, as the homozygous combination of GCdel haplotype was also found with raised susceptibility to Pott's disease (Pc=0.03). Our findings confirm and replicate the recent data from China (which dealt essentially with rs1024611 and rs2857656) and also reinforce them by providing trans-ethnic evidence and extending the genetic association to the rs3917887.


Safety and efficacy of bronchial thermoplasty in Australia 5 years post-procedure.
Outside clinical trials, there is limited long-term data following bronchial thermoplasty (BT). In a cohort of real-world severe asthmatics in an era of biological therapy, we sought to evaluate the safety and efficacy of BT 5 years post-treatment. Every patient treated with BT at two Australian tertiary centres were recalled at 5 years, and evaluated by interview and record review, Asthma Control Questionnaire (ACQ), spirometry and high-resolution CT Chest. CT scans were interpreted using the modified Reiff and BRICS CT scoring systems for bronchiectasis. Fifty-one patients were evaluated. At baseline, this cohort had a mean age of 59.0 ± 11.8 years, mean ACQ of 3.0 ± 1.0, mean FEV1 of 55.5 ± 18.8% predicted, and 53% were receiving maintenance oral steroids in addition to triple inhaler therapy. At 5 years, there was a sustained improvement in ACQ scores to 1.8 ± 1.0 (p < 0.001). Steroid requiring exacerbation frequency was reduced from 3.8 ± 3.6 to 1.0 ± 1.6 exacerbations per annum (p < 0.001). 44% of patients had been weaned off oral steroids. No change in spirometry was observed. CT scanning identified minor degrees of localized radiological bronchiectasis in 23/47 patients with the modified Reiff score increasing from 0.6 ± 2.6 at baseline to 1.3 ± 2.5 (p < 0.001). However, no patients exhibited clinical features of bronchiectasis, such as recurrent bacterial infection. Sustained clinical benefit from BT at 5 years was demonstrated in this cohort of very severe asthmatics. Mild, localized radiological bronchiectasis was identified in a portion of patients without clinical features of bronchiectasis.


Sex determination compared in Drosophila and Caenorhabditis.
Fruitflies and nematodes show many similarities in the general organization of the gene networks that control sexual dimorphism and dosage compensation. In contrast, the underlying molecular mechanisms appear to be very different in these two species. Developmental processes such as sex determination need not be strongly conserved in evolution.


Floating dosage forms to prolong gastro-retention--the characterisation of calcium alginate beads.
Floating calcium alginate beads, designed to improve drug bioavailability from oral preparations compared with that from many commercially available and modified release products, have been investigated as a possible gastro-retentive dosage form. A model drug, riboflavin, was also incorporated into the formula. The aims of the current work were (a) to obtain information regarding the structure, floating ability and changes that occurred when the dosage form was placed in aqueous media, (b) to investigate riboflavin release from the calcium alginate beads in physiologically relevant media prior to in vivo investigations. Physical properties of the calcium alginate beads were investigated. Using SEM and ESEM, externally the calcium alginate beads were spherical in shape, and internally, air filled cavities were present thereby enabling floatation of the beads. The calcium alginate beads remained buoyant for times in excess of 13h, and the density of the calcium alginate beads was <1.000gcm(-3). Riboflavin release from the calcium alginate beads showed that riboflavin release was slow in acidic media, whilst in more alkali media, riboflavin release was more rapid. The characterisation studies showed that the calcium alginate beads could be considered as a potential gastro-retentive dosage form.


Survival and readmission among patients with advanced cardiomyopathy undergoing transcatheter edge-to-edge mitral valve repair: Are we applying COAPT findings too broadly?
Transcathether edge-to-edge mitral valve repair (TEER) has been shown to be an effective treatment for secondary mitral regurgitation (MR). However, the outcomes of TEER in patients with severe cardiomyopathy is less clear. The objective of this study is to determine the outcomes of such patients who underwent TEER at our institution. A retrospective review of patients with severe cardiomyopathy, defined as ejection fraction ≤30% or the requirement of inotropic support preoperatively, undergoing TEER for secondary MR at our institution from 11/2016 to 11/2020 was performed. Univariate analysis associating preoperative characteristics with our primary endpoint of 1-year death or orthotopic heart transplant (OHT) was performed. Kaplan-Meier analysis was conducted for the composite outcome of death or OHT, as well as for heart failure-related readmission. Finally, an assessment of changes in MR severity from the preoperative, to immediate postoperative period, to 30-day postoperative period was conducted. There were 48 patients identified. Median age was 74.5 years (IQR 65.5-79.5), median ejection fraction was 21.5% (IQR 16.0-27.5), and 81.4% of patients had severe or torrential mitral regurgitation preoperatively. The composite endpoint of 1-year mortality or OHT occurred in 15 of 48 patients (31.3%, 14 deaths and 1 OHT). One-year heart failure readmission rate was 47.9%. Mortality or OHT at 2 years occurred in 45.8%. Patients at extremes of heart failure who underwent TEER had poor outcomes when assessed at 1-year. Our study may suggest that the results of cardiovascular outcomes assessment of the mitraclip percutaneous therapy for heart failure patients with secondary mitral regurgitation may not be applicable to patients with severe cardiomyopathy.


Prevalence and risk factors associated with vertebral osteoporotic fractures in patients with rheumatoid arthritis.
To explore the prevalence and risk factors of osteoporosis (OP) and vertebral osteoporotic fracture (VOPF) in patients with rheumatoid arthritis (RA). Anteroposterior and lateral X-ray examination of the vertebral column (T4-L4) was used for the semi-quantitative assessment of VOPF. Bone mineral density was measured by dual-energy X-ray absorptiometry. Of 865 RA patients, the prevalence of OP and VOPF was 33.6% and 20.2%, respectively. Patients with OP or VOPF were older, and had longer term use and a larger daily amount and cumulative dose of glucocorticoids (GCs), longer disease duration, and higher Health Assessment Questionnaire (HAQ) scores and Sharp scores than patients without OP or VOPF (P < 0.05). OP was also correlated with higher disease activity. The patients treated with GCs had higher incidences of OP and VOPF than the patients without GCs (P < 0.05). The cutoff values in the area under curve (AUC) of the daily dose or treatment course of GCs-VOPF were 9 mg and 37.5 days. Older age, female sex, and a higher Sharp score were risk factors for OP in RA patients, while higher BMI was a protective factor. Older age and a high GC daily dose were risk factors for VOPF in RA patients. RA patients have a high prevalence of OP and VOPF. Older age, female sex, lower BMI, and higher activity and severity of RA are closely related with OP. Older age and a higher GC daily dose are risk factors for VOPF in RA patients. Key Points • Older age, female sex, lower BMI, and a higher Sharp score were risk factors for OP in RA patients. • Older age and a high GC daily dose were risk factors for VOPF in RA patients. • OP and VOPF in RA patients were correlated with longer disease duration and higher severity of RA.


Intrusive luxation in primary teeth - Review of literature and report of a case.
Luxation injuries such as intrusion are commonly seen in the primary dentition. Intrusion drives the tooth deeper into the alveolar socket, which results in damage to the pulp and peridontium. Difficulty in gaining compliance from a very young child and the risk of damaging the permanent tooth germ makes the management of these injuries challenging. Careful clinical and radiographic examination along with regular follow-up is essential. A case of intrusive luxation to the maxillary central incisor in a 3-year-old patient is reported. Spontaneous reeruption was noted 4 months after injury, but the tooth had developed an abscess and external root resorption. Hence, extraction of the tooth was done and an anterior esthetic fixed space maintainer was placed. Traumatic injuries to the primary dentition should not be ignored by the parents or by the dentist. The paper also includes a literature review of intrusive luxation in the primary dentition.


Repeated transfer enriches highly active electrotrophic microbial consortia on biocathodes in microbial fuel cells.
Cathodic oxygen reduction catalyzed by autotrophic bacteria instead of a precious metal is a promising method to make use of microbial fuel cells (MFCs) in wastewater treatment with electricity production. However, the ecology of electrotrophic microbial consortia in wastewater systems that function as the catalyst for cathodic oxygen reduction is complicated and the electron transfer mechanisms are still unknown, which prevents further improvements of the biocathode performance. Enriched by the repeated transfer of a mature electrotrophic microbial consortia to new cathodes over 10 generations in 230 days, the start-up time was shortened from 21.4 to 7.6 days and the maximum current densities over the potential range of 0.5 to - 0.3 V increased by up to 112%, from 75 ± 5 A m-3 to 159 ± 3 A m-3, which was further confirmed in half-cell biocathode systems. The electrotrophic microbial consortia approached a relatively stable state after 8 generations. Acinetobacter, which is a member of Proteobacteria, was selectively enriched after 10 generations, which was closely related to the current production. Nitrospiraceae and Nitrosomonas may jointly perform a nitrogen cycling metabolic process and promote cathodic bioelectron transfer. Our findings confirmed that the electrotrophic microbial consortia on the cathode was able to be specifically evolved, leading to higher electroactivity, and also revealed which bacteria in fresh water are closely related to cathodic electron transfer.


Multimodal MRI-based Imputation of the Aβ+ in Early Mild Cognitive Impairment.
To identify brain atrophy from structural-MRI and cerebral blood flow(CBF) patterns from arterial spin labeling perfusion-MRI that are best predictors of the Aβ-burden, measured as composite 18F-AV45-PET uptake, in individuals with early mild cognitive impairment(MCI). Furthermore, to assess the relative importance of imaging modalities in classification of Aβ+/Aβ- early mild cognitive impairment. Sixty-seven ADNI-GO/2 participants with early-MCI were included. Voxel-wise anatomical shape variation measures were computed by estimating the initial diffeomorphic mapping momenta from an unbiased control template. CBF measures normalized to average motor cortex CBF were mapped onto the template space. Using partial least squares regression, we identified the structural and CBF signatures of Aβ after accounting for normal cofounding effects of age, sex, and education. 18F-AV45-positive early-MCIs could be identified with 83% classification accuracy, 87% positive predictive value, and 84% negative predictive value by multidisciplinary classifiers combining demographics data, ApoE ε4-genotype, and a multimodal MRI-based Aβ score. Multimodal-MRI can be used to predict the amyloid status of early-MCI individuals. MRI is a very attractive candidate for the identification of inexpensive and non-invasive surrogate biomarkers of Aβ deposition. Our approach is expected to have value for the identification of individuals likely to be Aβ+ in circumstances where cost or logistical problems prevent Aβ detection using cerebrospinal fluid analysis or Aβ-PET. This can also be used in clinical settings and clinical trials, aiding subject recruitment and evaluation of treatment efficacy. Imputation of the Aβ-positivity status could also complement Aβ-PET by identifying individuals who would benefit the most from this assessment.


Effects of BL 23 (Shenshu) acupuncture on serum cytokine levels in healthy adults: A randomized double-blind sham-controlled phase 1 study.
The purpose of this study was to evaluate the safety and efficacy of BL 23 (Shenshu) acupuncture on serum cytokine levels. Sixteen healthy adults were randomized into the BL 23 acupuncture group or pseudo-acupuncture group and changes of serum cytokines were analyzed. The changes in IL-13, TNF-α, and GM-CSF levels were different between the BL 23 acupuncture group and pseudo-acupuncture group (P < 0.05). No adverse events associated with acupuncture were observed. In conclusion, BL 23 acupuncture can suppress immune responses via decreases in TNF-α and suppression of increases in IL-13 and GM-CSF. This study elucidated some of the mechanisms of the acupuncture effect.


Analysis of the relationship between psychological gender and risk perception style and attitudes towards safety in a group of women and men.
The aim of the research was to analyse the relationship between psychological gender and risk perception style and the manifestation of pro-safe attitudes. The study involved 507 people in the age range 20-64 years, including 257 women and 250 men. Variables were measured using the following methods: Znajmiecka-Sikora's questionnaire of attitudes towards safety (PwB), Zaleśkiewicz's questionnaire of the individual risk perception style (SIRI) and Lipińska-Grobelny and Gorczycka's scale of masculinity and femininity (SMiK). The obtained results prove that psychological gender significantly differentiates risk perception style and attitudes towards safety. The feminine dimension has been shown to strengthen safe attitudes and minimize risk-taking, while the masculine dimension weakens attitudes towards safety and strengthens risk propensity.


Osmotic dehydration with sorbitol combined with hot air convective drying of apple cubes.
The aim of the present work was to study the effect of the osmotic dehydration (OD) pre-treatment on the mass transfer kinetics and water activity (aw) of apple cubes during hot air drying. The adequacy of different mathematical models to describe the moisture content of the product during this process was also evaluated. Apple cubes were osmotically dehydrated with sucrose or sorbitol solutions at 60 °C, and then dried by air at 25-80 °C. Overall, the OD and rise of the air temperature resulted in an increased water loss rate and a reduction of the aw. The osmotic agent used in the OD was not relevant to the air drying kinetics, but the pre-treatment with sorbitol solutions produced dried samples with lower aw. Newton's, Page's, modified Page's, Henderson and Pabis', Two-term, Two-term exponential, Logarithmic, Midilli et al.'s models could describe the moisture content well during the air drying process.


Comparison of combined versus subdural or intracerebral electrodes alone in presurgical focus localization.
The yield of subdural versus intracerebral electrodes for ictal localization remains a point of controversy. We assessed the relative sensitivity of these two types of electrodes per case. Eighty-three intracranial recordings obtained from 82 patients were retrospectively reviewed to establish which type of electrode performed best in which patients and which seizure types. Sixty (73%) of 82 patients had temporal lobe seizure onsets, eight frontal, nine widespread or multifocal/multilobar or both, whereas in five, seizure onset was not localized. Exclusive use of intracerebral electrodes would have been sufficient for accurate localization of the seizure-onset zone in all 35 patients with strictly mesial temporal seizure onsets. In only 20 (57%) of these 35 patients, the same decision would have been reached with exclusive use of subdural electrodes. In widespread neocortical and mesial temporal seizures (n = 25), yield of both electrode types was at about the same level, but neither was sufficient to identify the zone of ictal onset on its own. In frontal or multilobar seizures (n = 22), yield of subdural electrodes was slightly better then that of the intracerebral electrodes, but was not sufficient in all cases. This study indicates that, depending on the characteristics of the seizure disorder, exclusive use of either intracerebral or subdural electrodes may easily result in erroneous diagnosis because of insufficient sampling of the brain. These findings are in contrast with other studies emphasizing the high yield of reliable EEG findings in evaluations with a single type of electrode and corroborate the results of one of our previous studies.


Latency locus complements MicroRNA 155 deficiency in vivo.
MicroRNA-155 (miR-155) is expressed in many cancers. It also executes evolutionary conserved functions in normal B cell development. We show that the Kaposi's sarcoma-associated herpesvirus (KSHV) latency locus, which contains an ortholog of miR-155, miR-K12-11, complements B cell deficiencies in miR-155 knockout mice. Germinal center (GC) formation was rescued in spleen, lymph node, and Peyer's patches. Immunoglobulin levels were restored. This demonstrates that KSHV can complement the normal, physiological function of miR-155.


The impact of war on reproductive medicine in Ukraine.
Reproductive medicine plays a vital role in ensuring the health and well-being of individuals and families. However, the ongoing assault of Russia on Ukraine has disrupted the provision of healthcare services in Ukraine, including of reproductive medicine. The impact of the war on the state of reproductive medicine can provide valuable insights into the challenges faced by healthcare providers and policy makers in war-affected areas. This article explores the situation of reproductive medicine in Ukraine after the Russian attack on Ukraine and the full-scale war on 24 February 2022, including changes in the availability and quality of services and the challenges faced by healthcare providers and patients. IVF clinics face significant challenges in safeguarding the fate of cryopreserved embryos and reproductive cells. To address these challenges, clinics need to take measures to ensure their facilities' safety and security, maintain continuity of operations, and navigate ethical and legal dilemmas related to patients' reproductive material. By examining the available data and insights from healthcare providers and patients, this article will contribute to the broader understanding of the impact of war on reproductive health and the importance of ensuring access to essential healthcare services in war-affected areas.


Sjögren-Larsson syndrome in Sweden: distribution of the gene.
The distribution of carriers of the gene for Sjögren-Larsson syndrome in Sweden suggests a center of dispersion in the county of Västerbotten in Northern Sweden. The origin of the spread of the gene can be traced back at least 700 years.


Methyl donors potentiates growth, metabolic status and neurotransmitter enzyme in Labeo rohita fingerlings exposed to endosulfan and temperature.
A 2-month preliminary study was conducted to delineate the effect of dietary methyl donors (choline, betaine, and lecithin) on the growth performance and metabolic status of Labeo rohita fingerlings subjected to endosulfan alone and in combination with elevated temperature. Four iso-caloric and iso-nitrogenous diets viz. basal diet, betaine-supplemented diet, choline-supplemented diet and lecithin-supplemented diet were prepared and fed to the different experimental groups throughout the experimental period as per the design. Two hundred and seventy fingerlings (average weight 7.95 ± 0.04 g) were randomly distributed in six treatment groups each having three replicates. The experimental groups were as follows: fish subjected to normal water (without endosulfan) and fed with control diet (control group T(0)), fish subjected to endosulfan-treated water and fed with control diet (T(1)), fish subjected to concurrent exposure of endosulfan and elevated temperature and fed with control diet (T(2)), fish subjected to endosulfan and elevated temperature and fed with choline-supplemented diet (T(3)), fish subjected to endosulfan and temperature and fed with betaine-supplemented feed (T(4)), and fish subjected to endosulfan and temperature and fed with lecithin-supplemented feed (T(5)). The result shows that in both the groups, that is, endosulfan exposed and concurrent exposure to endosulfan and elevated temperature group of L. rohita the growth performance like percentage weight gain, feed conversion ratio and specific growth rates were significantly different (P < 0.01) when fed with supplemented diet compared with control fed group. The liver LDH and MDH activity were significantly lower in lecithin, betaine, and choline fed groups. The muscle AST as well as G6PDH, AST, and ALT did not vary but liver ALT, gill and liver ATPase, intestine ALP, muscle and liver glycogen varied significantly with dietary supplementation. The liver and gill glutathione-S-transferase (GST) activities were significantly lower in methyl donors-supplemented groups and brain AChE activity showed lower inhibition in supplemented groups in both endosulfan alone and concurrently exposed endosulfan and temperature groups. The result obtained in this study concludes that inclusion of methyl donors, particularly lecithin and betaine in feed as nutritional supplements have potential to improve growth and stress mitigating effect in L. rohita fingerlings.


Solution-phase detection of dual microRNA biomarkers in serum.
A strategy for the simultaneous detection of multiple microRNA (miRNA) targets was developed utilizing fluorophore/quencher-labeled oligonucleotide probe sets. Two miRNA targets (miR-155 and miR-103), whose misregulation has afforded them status as putative biomarkers in certain types of cancer, were detected using our assay design. In the absence of target, the complementary fluorophore-probe and quencher-probe hybridize, resulting in a fluorescence resonance energy transfer-based quenching of the fluorescence signal. In the presence of unlabeled target, however, the antisense quencher-probe can hybridize with the target, resulting in increased fluorescence intensity as the quencher-probe is sequestered beyond the Förster radius of the fluorescent-probe. The assay design was tested in multiple matrices of buffer, cellular extract, and serum; and detection limits were found to be matrix-dependent, ranging from 0.34 to 8.89 pmol (3.4-59.3 nM) for miR-155 and 2.90-11.8 pmol (19.3-79.0 nM) for miR-103. Single, double, and triple nucleotide selectivity was also tested. Additionally, miR-155 concentrations were assessed in serum samples obtained directly from breast cancer patients without the need for RNA extraction. This assay is quantitative, possesses a low detection limit, can be applied in multiple complex matrices, and can obtain single-nucleotide selectivity. This method can be employed for the multiplex detection of solution-phase DNA or RNA targets and, more specifically, for the direct detection of serum miRNA biomarkers.


Serum adiponectin and progression of diabetic nephropathy in patients with type 1 diabetes.
The purpose of this study was to elucidate whether serum adiponectin is associated with progression of diabetic nephropathy in type 1 diabetic patients. This was a prospective follow-up study as a part of the nationwide Finnish Diabetic Nephropathy Study; 1,330 type 1 diabetic patients were followed for 5.0 +/- 2.2 years. Patients were divided at baseline into three groups according to their urinary albumin excretion rate (AER) in three consecutive overnight or 24-h urine collections: 818 patients with normoalbuminuria (AER <20 microg/min), 216 patients with microalbuminuria (20 microg/min <or= AER < 200 microg/min), and 296 patients with macroalbuminuria (AER >or=200 microg/min). Progression of albuminuria was the main outcome. Adiponectin was measured by a time-resolved immunofluorometric assay, and the values were log-transformed and adjusted for age, BMI, and sex before analysis. Progression either to the next albuminuria level or to end-stage renal disease (ESRD) occurred in 193 patients. No difference in adiponectin concentrations was observed between progressors and nonprogressors in patients with normoalbuminuria or microalbuminuria. In the patients with macroalbuminuria, progression to ESRD was associated with higher adiponectin in the entire group (23.4 +/- 17.1 vs. 16.0 +/- 8.5 mg/l, P < 0.001) and in men (P < 0.001) and women (P < 0.001) separately. Progression to ESRD was also associated with systolic blood pressure, insulin dose, A1C, serum cholesterol, serum triglycerides, AER, and estimated glomerular filtration rate (eGFR). When these covariates were inserted in a Cox regression analysis, A1C, triglycerides, eGFR, and adiponectin were significantly associated with progression from macroalbuminuria. Increased serum adiponectin levels predict the progression from macroalbuminuria to ESRD in type 1 diabetic patients.


Tumor-associated macrophages of the M2 phenotype contribute to progression in gastric cancer with peritoneal dissemination.
Tumor-associated macrophages (TAMs) of the M2 phenotype are known to promote tumor proliferation and to be associated with a poor prognosis in numerous cancers. Here, we investigated whether M2 macrophages participate in the development of peritoneal dissemination in gastric cancer. The characteristics of peritoneal macrophages in gastric cancer patients with or without peritoneal dissemination were examined by flow cytometry and the real-time quantitative polymerase chain reaction. The effects of M2 macrophages on phenotypic changes of the gastric cancer cell line MKN45 were assessed with a direct or indirect co-culture system in vitro and an in vivo mouse xenograft model. The number of peritoneal macrophages with the M2 phenotype (CD68(+)CD163(+) or CD68(+)CD204(+)) was significantly higher in gastric cancer patients with peritoneal dissemination than in those without peritoneal dissemination. Higher expression of the M2-related messenger RNAs (IL-10, vascular endothelial growth factor A, vascular endothelial growth factor C, matrix metalloproteinase 1, and amphiregulin) and lower expression of M1-related messenger RNAs (TNF-α, CD80, CD86, and IL-12p40) were also confirmed in the TAMs. Macrophage co-culture with gastric cancer cells converted M1 phenotype into M2 phenotype. Moreover, the coexistence of MKN45 cells with M2 macrophages resulted in cancer cell proliferation and an acceleration of tumor growth in the xenograft model. Intraperitoneal TAMs in gastric cancer patients with peritoneal dissemination were polarized to the M2 phenotype, and could contribute to tumor proliferation and progression. Therefore, intraperitoneal TAMs are expected to be a promising target in the treatment of peritoneal dissemination in gastric cancer.


Associations between testosterone, estradiol, and androgen receptor genotype with amygdala subregions in adolescents.
Much is known about the development of the whole amygdala, but less is known about its structurally and functionally diverse subregions. One notable distinguishing feature is their wide range of androgen and estrogen receptor densities. Given the rise in pubertal hormones during adolescence, sex steroid levels as well as receptor sensitivity could influence age-related subregion volumes. Therefore, our goal was to evaluate the associations between the total amygdala and its subregion volumes in relation to sex hormones - estradiol and free testosterone (FT) - as a function of age and genetic differences in androgen receptor (AR) sensitivity in a sample of 297 adolescents (46% female). In males, we found small effects of FT-by-age interactions in the total amygdala, portions of the basolateral complex, and the cortical and medial nuclei (CMN), with the CMN effects being moderated by AR sensitivity. For females, small effects were seen with increased genetic AR sensitivity relating to smaller basolateral complexes. However, none of these small effects passed multiple comparisons. Future larger studies are necessary to replicate these small, yet possibly meaningful effects of FT-by-age associations and modulation by AR sensitivity on amygdala development to ultimately determine if they contribute to known sex differences in emotional neurodevelopment.


Identity, Representations, and Beliefs: HIV Controllers Living on the Frontier of Good Health and Illness.
Some people living with HIV spontaneously control the virus without antiretroviral treatment. They are called HIV controllers, and their status places them at the limits of bio-clinical normality. The objective of this study was to investigate HIV controllers' beliefs and representations of their individual trajectories using a qualitative approach. Fourteen HIV controllers were interviewed. Vertical analysis focused on examining how interviewees' specific beliefs and representational processes help these patients adapt to their particular situation. Horizontal analysis focused on how patients' biographic trajectories and identity positioning help them make sense of their situation. Results highlighted that perceiving oneself to be healthy or ill was linked to change or a lack of change in terms of disease perception, beliefs, and representations, when seropositivity was announced. This study of social representations and the processes involved provide crucial elements for health professionals caring for HIV controllers.


[Staphylococcal pneumonia in a premature neonate: unusual transmission of nosocomial infection].
Late onset of neonatal infection could have been transmitted in prenatal period, but it is usually secondary to a postnatal transmission. A premature neonate developed staphylococcal pneumonia at 18 days of life. Genomic typing of the strains of Staphylococcus aureus obtained from the patient and from his mother (found in the endocervix culture 48 h before delivery) was identical. These strains were different from those isolated in other neonates colonised by S. aureus in the unit during at that moment. The observed case of staphylococcal pneumonia may correspond to a nosocomial infection secondary to a pre- or postnatal transmission of the agent by the mother.


Steady-state sequence optimization with incremental input constraints in two-layer model predictive control.
Steady-state optimization is of vital importance in two-layer model predictive control for bringing better steady-state and dynamic performance. However, the global optimality of steady-state sequences provided by local steady-state optimization cannot be guaranteed. Therefore, a new steady-state sequence optimization approach is proposed in the paper, to improve the global optimality of steady-state sequences. First, the non-global optimality of local steady-state sequences is discussed using an example. Subsequently, aiming at improving the global optimality, a novel sequence optimization strategy designed for steady-state optimization is proposed. Its basic formulation is given and the lower bound of the introduced parameter is analyzed. Then, the relation and difference between the proposed steady-state sequence optimization and the existing global steady-state optimization and local steady-state optimization are discussed. Finally, the steady-state performance, dynamic performance, and computational burden of the proposed approach are studied. The proposed approach provides engineers a brand-new way to realize steady-state optimization and effectively improves the global optimality of calculated steady-state sequences. Extensive simulations verify the effectiveness and reliability of the proposed method.


Effect of Beta vulgaris Linn. Leaves Extract on Anxiety- and Depressive-like Behavior and Oxidative Stress in Mice after Acute Restraint Stress.
Stress plays a significant role in the pathogenesis of neuropsychiatric disorders such as anxiety and depression. Beta vulgaris is commonly known as "beet root" possessing antioxidant, anticancer, hepatoprotective, nephroprotective, wound healing, and anti-inflammatory properties. To study the protective effect of Beta vulgaris Linn. ethanolic extract (BVEE) of leaves against acute restraint stress (ARS)-induced anxiety- and depressive-like behavior and oxidative stress in mice. Mice (n = 6) were pretreated with BVEE (100 and 200 mg/kg, p. o.) for 7 days and subjected to ARS for 6 h to induce behavioral and biochemical changes. Anxiety- and depressive-like behavior were measured by using different behavioral paradigms such as open field test (OFT), elevated plus maze (EPM), forced swim test (FST), and tail suspension test (TST) 40 min postARS. Brain homogenate was used to analyze oxidative stress parameters, that is, malondialdehyde (MDA) and reduced glutathione (GSH) level. BVEE pretreatment significantly (P < 0.05) reversed the ARS-induced reduction in EPM parameters, that is, percentage entries and time spent in open arms and in OFT parameters, that is, line crossings, and rearings in mice. ARS-induced increase in the immobility time in FST and TST was attenuated significantly (P < 0.05) by BVEE pretreatment at both the dosage. An increase in MDA and depletion of GSH level postARS was prevented significantly (P < 0.05) with BVEE pretreatment at both the dosage (100 and 200 mg/kg). BVEE exhibits anxiolytic and antidepressant activity in stressed mice along with good antioxidant property suggesting its therapeutic potential in the treatment of stress-related psychiatric disorders. Stress plays major role in the pathogenesis of anxiety and depressionARS-induced anxiety- and depressive-like behavior through oxidative damage in miceBVEE pretreatment reversed ARS-induced behavioral changes, that is, anxiety and depressionARS-induced oxidative stress was prevented by BVEE pretreatment in mice. Abbreviations Used: Analysis of variance, ARS: Acute restraint stress, BVEE: Beta vulgaris ethanolic extract, BV: Beta vulgaris, CMC: Carboxymethylcellulose, CNS: Central nervous system, CPCSEA: Committee for the purpose of control and supervision of experiments on animals, cms: Centimeter, DNA: Deoxyribose nucleic acid, EPM: Elevated plus maze, FST: Forced swim test, GSH: Reduced glutathione, g: Gram, h: Hour, IAEC: Institutional Animal Ethics Committee, mg: Milligram, μM: Microgram, MDA: Malondialdehyde, SEM: Standard error of mean, TST: Tail suspension test, UV: Ultraviolet, w/v: Weight by volume.


Gene expressing analysis indicates the role of Pyrogallol as a novel antibiofilm and antivirulence agent against Acinetobacter baumannii.
Acinetobacter baumannii has emerged worldwide as a leading cause of hospital-acquired infections. Although A. baumannii was initially regarded to as a low-grade pathogen, evidence has been accumulated suggesting that A. baumannii infections are associated with increased mortality in critically ill patients. Here, we describe the efficacy of pyrogallol, a polyphenolic organic compound found in the galls and barks of various trees, which shows anti-biofilm and anti-virulence potential against A. baumannii. Pyrogallol shows concentration-based biofilm inhibition, as evidenced through light and confocal laser scanning microscopic analysis. The other virulence factors are protease, swarming motility, and extracellular polymeric substances that are also inhibited by pyrogallol. Through real-time PCR, it was found that pyrogallol downregulates expression of the biofilm and virulence-related ompA, bap, csuA/B, katE, pgaA, and pgaC genes. Furthermore, pyrogallol moderately inhibited the mature biofilms of A. baumannii in a concentration-dependent manner (5, 10, and 20 µg/ml). The present study reports that the anti-biofilm and anti-virulence potential of pyrogallol disrupts the biofilm formation, adherence of cells, and cell-to-cell signaling mechanism of A. baumannii. Thus, pyrogallol is a promising therapeutic agent for A. baumannii-related infections.


Temporally defined induction of c-fos in the rat pineal.
In the rat pineal gland c-fos is transiently and markedly induced after the onset of darkness. The induction is abolished following removal of the superior cervical ganglion and reproduced in ganglionectomized animals by treatment with the adrenergic agonist isoproterenol. These findings show for the first time that induction of c-fos forms an integral part of physiological changes in cellular activity. Expression of the c-fos gene may be functionally linked to the nocturnal changes in pineal indole metabolism.


Depolarization- and agonist-regulated expression of neuronal metabotropic glutamate receptor 1 (mGluR1).
In established 8-12-day-old primary cultures of differentiated rat cerebellar granule neurons the level of metabotropic glutamate receptor 1 (mGluR1) mRNA and the sensitivity of cultures to the agonist-stimulated inositol phosphate (IP) formation was reversibly modified by changing the depolarizing properties of the medium, i.e. the medium KCl concentration. The mGluR1 mRNA content was suppressed by increasing the medium KCl content and elevated by decreasing it. The mGluR agonist quisqualate inhibited the mGluR1 expression. This is the first direct demonstration of a differential expression of neuronal mGluR1 in an established neuronal culture. The model can be used to study the molecular mechanism of neuronal plasticity.


Phagocytic and bactericidal activity of blood and milk-resident neutrophils against Staphylococcus aureus in primiparous and multiparous cows during early lactation.
To examine the effect of parity on polymorphonuclear neutrophils (PMN) function, phagocytic and bactericidal activity of the PMN isolated from blood and milk against Staphylococcus aureus was compared between groups of 6 primiparous and 6 multiparous healthy dairy cows during early lactation using bacteriological and PMN-pathogen interaction assays. Latex-stimulated luminol-amplified chemiluminescence (CL) and viability of these PMN were also investigated. The phagocytosis and killing of S. aureus by blood were remarkably higher than those of milk PMN. Similarly, the CL and viability in blood PMN were markedly higher than in milk PMN. Both in blood and in milk the phagocytosis of S. aureus by PMN in primiparous cows was substantially higher than in multiparous cows. The killing activity of blood PMN against S. aureus was 42.3+/-3.4% and 23.2+/-1.7% in primiparous and multiparous, respectively. Milk PMN killed only 20.7+/-2% S. aureus in primiparous and 10.2+/-1.3% in multiparous cows. Blood and milk PMN CL and milk PMN viability were significantly higher in primiparous cows. The pronounced reduction in phagocytic and bactericidal activity in blood and milk-resident PMN from multiparous cows, in part, resulted from the pronounced decrease of PMN viability and free radicals production capacity; this suggests that heifers' udders could be more protected against S. aureus, which remains to be tested in the field.


The Vasodilator Effect of a Cream Containing 10% Menthol and 15% Methyl Salicylate on Random-Pattern Skin Flaps in Rats.
It is still difficult to prevent partial or full-thickness flap necrosis. In this study, the effects of a cream containing menthol and methyl salicylate on the viability of randompattern skin flaps were studied. Forty female Sprague-Dawley rats were divided into two equal groups. Caudally based dorsal random-pattern skin flaps were elevated, including the panniculus carnosus. In the study group, 1.5 mL of a cream containing menthol and methyl salicylate was applied to the skin of the flap, and saline solution (0.9%) was used in the control group. Upon completion of the experiment, flap necrosis was analyzed with imaging software and radionuclide scintigraphy. Histopathological measurements were made of the percentage of viable flaps, the number of vessels, and the width of the panniculus carnosus muscle. According to the photographic analysis, the mean viable flap surface area in the study group was larger than that in the control group (P=0.004). According to the scintigrams, no change in radioactivity uptake was seen in the study group (P>0.05). However, a significant decrease was observed in the control group (P=0.006). No statistically significant differences were observed between the groups in terms of the percentage of viable flaps, the number of vessels, or the width of the panniculus carnosus muscle (P>0.05). Based on these results, it is certain that the cream did not reduce the viability of the flaps. Due to its vasodilatory effect, it can be used as a component of the dressing in reconstructive operations where skin perfusion is compromised.


Direct and indirect methods of measuring Helicobacter pylori drug susceptibility in vitro.
This article outlines a number of methods for the determination of inhibitory and bactericidal activity against H. pylori. Direct methods rely on the ability of bacteria to divide and multiply and ultimately form visible colonies after subjection to antibiotic treatment. Indirect methods rely on the measurement of metabolic activity as a viability marker and are much more rapid, especially taking into account the slow growth and fastidious nature of the organism. Inhibitory concentration measurement does not indicate the bactericidal ability of a drug; inhibition of growth does not necessarily correlate with cell death. Theoretical generation of viable but nonculturable bacteria could bring in to question the validity of direct measurements based on the colony forming ability of an organism posttreatment.


Harmful effects and acute lethal toxicity of intravenous administration of low concentrations of hydrofluoric acid in rats.
The acute toxicity of hydrofluoric acid (HFA) was investigated in a 24-h lethal dose study of intravenous infusion in rats. The lethal dose lowest (LDLo) and LD50 were 13.1 and 17.4 mg/kg, respectively. Harmful systemic effects were also studied 1 h after acute sublethal exposure to HFA. The maximum dose was set at 9.6 mg/kg (LD5). Rats were injected with HFA (1.6, 3.2, 6.4 or 9.6 mg/kg), saline, sodium fluoride (NaF) or HCl solution. NaF and HCl solution concentrations corresponded to the F- and H+ concentrations of 9.6 mg/kg HFA. Blood urea nitrogen (BUN) and Cr were significantly increased in response to HFA concentrations greater than 3.2mg/kg. Acute glomerular dysfunction also occurred at HFA concentrations greater than 3.2 mg/kg. HCO3- and base excess (BE) were significantly decreased in the 6.4 and 9.6 mg/kg groups. Ca2+ was significantly decreased, and K+ was increased in the 9.6 mg/kg group. BUN was significantly increased in the NaF and HFA groups and was increased in the HFA group compared with that in the NaF group. Cr was significantly increased in the HFA group only. HCO3- and BE were significantly decreased in the NaF and HFA groups and were increased in the HFA group compared with values in the NaF group. Ca2+ was significantly decreased in the NaF and HFA groups, and K+ was significantly increased in the NaF and HFA groups. F- exposure directly affected serum electrolytes. Mortality was thought to be due to cardiac arrhythmia resulting from hypocalcemia and hyperkalemia. Metabolic acidosis and renal failure were more severe in response to HFA exposure than in response to NaF exposure because of more free F-, which has strong cytotoxicity, in the HFA group than in the NaF group. Lethal effects of HFA are promoted by exposure routes such as inhalation that cause rapid absorption into the body. Even low exposure to HFA can cause acute renal dysfunction, electrolyte abnormalities and metabolic acidosis. These complications result in a poor prognosis.


Transition of Temporal Scaling Behavior in Percolation Assisted Shear-branching Structure during Plastic Deformation.
This paper explores the temporal scaling behavior induced shear-branching structure in response to variant temperatures and strain rates during plastic deformation of Zr-based bulk metallic glass (BMG). The data analysis based on the compression tests suggests that there are two states of shear-branching structures: the fractal structure with a long-range order at an intermediate temperature of 223 K and a larger strain rate of 2.5 × 10-2 s-1; the disordered structure dominated at other temperature and strain rate. It can be deduced from the percolation theory that the compressive ductility, ec, can reach the maximum value at the intermediate temperature. Furthermore, a dynamical model involving temperature is given for depicting the shear-sliding process, reflecting the plastic deformation has fractal structure at the temperature of 223 K and strain rate of 2.5 × 10-2 s-1.


Nevus depigmentosus: the analysis of 37 cases.
Nevus depigmentosus (ND) is an uncommon congenital nonprogressive hypopigmented skin disorder that can be seen anywhere on the body. We considered other depigmenting disorders and focused on distinguishing ND from vitiligo and tuberous sclerosis complex in infancy. The diagnosis of patients with nevus depigmentosus was made differentiating it from nevus anemicus, pityriasis alba, tuberous sclerosis complex, vitiligo and other depigmenting disorders. Of the 37 individuals with nevus depigmentosus evaluated, 36 were children, twenty-two (59.4%) were males and 15 (40.5%) were females, with male to female ratio 1.4:1. Distinguishing ND from other disorders with depigmentation can be challenging, in particular in case of tuberous sclerosis complex and vitiligo in infancy.


New techniques of analyzing the healing process of artificial vascular grafts, transmural vascularization, and endothelialization.
Beside traditional techniques (light, immunofluorescence, transmission electron (TEM)- and scanning electron microscopy (SEM), a new more sensitive method for producing microcorrosion casts using a polyester-based resin has been developed. The SEM analyses of the microcorrosion casts of alloplastic vascular grafts was realized in an absolutely stable stage of polymerization. For the first time, a transprosthetic vascularization could be shown in great three-dimensional detail. The importance of a complete and rapid endothelialization of artificial vascular grafts is discussed.


Missense meanderings in sequence space: a biophysical view of protein evolution.
Proteins are finicky molecules; they are barely stable and are prone to aggregate, but they must function in a crowded environment that is full of degradative enzymes bent on their destruction. It is no surprise that many common diseases are due to missense mutations that affect protein stability and aggregation. Here we review the literature on biophysics as it relates to molecular evolution, focusing on how protein stability and aggregation affect organismal fitness. We then advance a biophysical model of protein evolution that helps us to understand phenomena that range from the dynamics of molecular adaptation to the clock-like rate of protein evolution.


Isolated Tricuspid Valve Surgery: The Auckland Experience 2011-2019.
Isolated tricuspid valve surgery is an uncommon operation. Historical reports, including a previous review from our unit, demonstrated high morbidity and mortality associated with this operation. Many of these patients had severely impaired right ventricular function at the time of the surgery. Since our previous review, we have actively encouraged our local cardiologists to refer patients with severe isolated tricuspid disease for surgery before right ventricular remodelling occurs. This present study was performed to assess our current results. A prospectively-maintained hospital database was used to identify all adult non-congenital patients receiving standalone tricuspid valve repair or replacement at New Zealand's largest cardiothoracic surgical unit from July 2011 to July 2019. Additional demographic and clinical data were collected by review of patient electronic records. During the 8-year study period, a total of 50 patients underwent isolated tricuspid valve surgery. Most patients were operated on for functional (40%) or rheumatic (30%) tricuspid disease. The majority of patients underwent surgery when the right ventricular function preoperatively was normal (30%) or mildly/moderately impaired (60%). Over half the patient sample (56%) underwent valve replacement. The 30-day mortality rate and stroke rate were 6% and 2% respectively. The medium-term survival was 80% at 4 years mean follow-up. Isolated tricuspid surgery is no longer a high mortality operation when it is performed on patients who have preserved right ventricular function.


Cerebral vasculitis associated with cocaine abuse.
A case of cerebral vasculitis in a previously healthy 22-year-old man with a history of cocaine abuse is described. Cerebral angiograms showed evidence of vasculitis. A search for possible causes other than cocaine produced no results. We now include cocaine with methamphetamines, heroin, and ephedrine as illicit drugs that can cause cerebral vasculitis.


Pulsed laser deposition of hydroxyapatite on nanostructured titanium towards drug eluting implants.
Titania nanotubes grown on titanium substrates by electrochemical anodization in glycerol-ammonium fluoride-water system were used to develop efficient drug carrying implants upon coating hydroxyapatite (HA) ceramic. The nanostructured surfaces achieved by anodization were caped with HA crystallites by pulsed laser deposition. The implant substrates were studied for their drug carrying capacity using gentamicin as a model. The nano-tubular surface with HA coating had better drug loading capacity of about 800 μg/cm(2) gentamicin while the bare anodized substrate carried less than 660 μg/cm(2). The HA coating alone stored as low as 68 μg/cm(2) and released the drug within the initial burst period itself. The ceramic coated anodized substrates were found to be more efficient in controlled delivery for longer than 160 h with a drug release of 0.5 μg/cm(2) even towards the end. The substrate with nanostructuring alone delivered the whole drug within 140 h. This study proposes the application of laser deposition of HA over nanostructured titanium, which proves to be promising towards controlled drug eluting bioceramic coated metallic prostheses.


Historical and bibliometric notes on the use of fluoride in caries prevention.
The aim of the present report was to highlight historical and bibliometric aspects of fluoride in dentistry. Study design: In the first part of the manuscript, history of fluoride has been reported. In the second part, some bibliometric considerations have been explained. The historical research evaluated the first documents about fluoride in dentistry. The bibliometric research considered Scopus-indexed documents from 1945 to 2019. Historical search showed the consistent presence of documents since 1803, even if modern research started in the 1930s. Descriptive statistics of documents about fluoride showed a constantly increasing interest on the topic, starting from 1965 to nowadays. The topic of fluoride has a long history in dental practice, and future interesting research is needed in order to combine this well-known inorganic, monatomic anion with new emerging technologies.


Intra-parotid Course and Variations in the Branching Pattern of Facial Nerve: Our Experience.
Facial nerve is responsible for the facial expressions and its preservation during parotidectomy is an important aspect for the operating surgeon. The nerve has a long course and the terminal part traverses through the parotid gland. The branching pattern of the nerve within the gland is highly complex and variable, making parotidectomy a challenging surgery. A cross-sectional record based study was conducted in a tertiary care hospital of a medical college in north India between November 2020 and December 2021 with an aim to describe the branching pattern of the facial nerve within the parotid gland. Patients of all age groups and both genders who underwent superficial parotidectomy for benign parotid gland tumors were taken into consideration. The branching pattern of the nerve was observed and recorded. Twenty patients were included in the study. In seventy percent cases the nerve divided into two main branches whereas in the rest, three branches emerged. In sixty five percent cases, the upper division (temporofacial) further divided into two branches whereas in rest it divided into three. The lower division (cervicofacial) divided into two subdivisions in majority of the cases. Multiple communications were found in the branches given off from the upper division and buccal branch had the most variable origin. A knowledge of branching pattern and the communications between the branches of facial nerve helps in avoiding an iatrogenic injury during parotidectomy and preserving the nerve function.


Arachidonate 5 lipoxygenase expression in papillary thyroid carcinoma promotes invasion via MMP-9 induction.
Arachidonate 5-lipoxygenase (ALOX5) expression and activity has been implicated in tumor pathogenesis, yet its role in papillary thyroid carcinoma (PTC) has not been characterized. ALOX5 protein and mRNA were upregulated in PTC compared to matched, normal thyroid tissue, and ALOX5 expression correlated with invasive tumor histopathology. Evidence suggests that PTC invasion is mediated through the induction of matrix metalloproteinases (MMPs) that can degrade and remodel the extracellular matrix (ECM). A correlation between MMP-9 and ALOX5 protein expression was established by immunohistochemical analysis of PTC and normal thyroid tissues using a tissue array. Transfection of ALOX5 into a PTC cell line (BCPAP) increased MMP-9 secretion and cell invasion across an ECM barrier. The ALOX5 product, 5(S)-hydroxyeicosatetraenoic acid also increased MMP-9 protein expression by BCPAP in a dose-dependent manner. Inhibitors of MMP-9 and ALOX5 reversed ALOX5-enhanced invasion. Here we describe a new role for ALOX5 as a mediator of invasion via MMP-9 induction; this ALOX5/MMP9 pathway represents a new avenue in the search for functional biomarkers and/or potential therapeutic targets for aggressive PTC.


Biochemical characterization of elastin in neointimal hyperplasia of rabbit aorta.
Elastin synthesized in response to vascular injury was characterized in terms of its amino acid composition, the biosynthetic labeling of the desmosines and of the heat coacervable polypeptides present in the 2 M urea extract. Neointimal hyperplasia of the chronic variety was induced in rabbit aorta by superficial mechanical lesions. At 4 months following injury the reendothelialized neointimal thickening and the media were excised. Aliquot samples were incubated with [3H] lysine, extracted with 2 M urea, 0.1 M Tris, pH 7.4 and hydrolysed with collagenase. In the residue of the digests the [3H] desmosines were quantified after electrophoretic separation. Elastin was purified from the nonlabeled aliquots of the media and neointimal hyperplasia. It accounted for 60% and 25% of the dry weight of the media and the neointima respectively. Elastin isolated from the media and the neointima had essentially the same amino acid composition. The incorporation of [3H] lysine into desmosines and into coacervable polypeptides indicated that the synthesis of crosslinked elastin is still active in the hyperplasia at 4 months following injury.


Knockdown of the tachykinin neurokinin 1 receptor by intrathecal administration of small interfering RNA in rats.
The contribution of tachykinin neurokinin 1 (NK₁) receptor to nociceptive processing in the dorsal horn has been evaluated by tachykinin NK₁ receptor antagonism and knockout or knockdown of tachykinin NK₁ receptor; however, these results have not always been consistent. Therefore, to reevaluate the role of tachykinin NK₁ receptor in the dorsal horn, a solution of hemagglutinating virus of the Japan envelope (HVJ-E) with small interfering RNA (siRNA) against tachykinin NK₁ receptor was administered intrathecally and then the effect of treatment on tachykinin NK₁ receptor immunohistochemistry and on the induction of inflammation, thermal hyperalgesia and scratching behavior was evaluated. This treatment resulted in marked reduction of tachykinin NK₁ receptor immunoreactivity through the spinal dorsal horn, and the induction of thermal hyperalgesia and scratching behavior by substance P was significantly attenuated in rats with tachykinin NK₁ receptor siRNA. In addition, only one intrathecal injection of tachykinin NK₁ receptor siRNA reduced carrageenan-induced inflammation and thermal hyperalgesia significantly and markedly attenuated the induction of flinching after formalin injection and c-Fos expression in the dorsal horn following formalin injection. The efficient down-regulation of tachykinin NK₁ receptor by intrathecal administration tachykinin NK₁ receptor siRNA suggests that this method may be a valuable tool for examining the function of genes expressed in the dorsal horn.


Chokeberry (Aronia melanocarpa) - A review on the characteristic components and potential health effects.
The intention of this review is to contribute to a better understanding of the potentials of the nutritional contribution of ARONIA berries ( ARONIA MELANOCARPA). The paper gives a short background to their botanical classification and cultivation practice, going in detail to describe the chemical composition of the berries. The emphasis is laid thereby upon the phenolic constituents. The paper finally gives a short resume of their beneficial effects in biological systems IN VITRO, in animals, and in humans, thus underlining their medicinal potential.


Renal and bone uptake of tartaric acid in rats: comparison of L(+) and DL-Forms.
Plasma concentrations of radioactivity declined biphasically with half-lives of about 15 and 58 h respectively in rats dosed with monosodium DL-[14C]tartrate for 7 days at a dose level of 2.73 g/kg/day. Uptake and retention of radioactivity occurred in blood cells, kidneys and bones where it was detected for at least 12 days after dosing. Renal retention (11202 +/- 4469 ppm at 6 h, n = 7) was probably due to precipitation of the poorly soluble calcium DL-tartrate in the tubules leading to increased kidney weight, nephrotoxicity and even death. The more soluble, naturally-occurring L(+)-[14C] tartrate was not retained in the kidneys (1287 +/- 118 ppm at 6 h, n = 8) when administered to rats under the same conditions, and the initial decline of plasma concentrations of radioactivity was more rapid (t 0.5 approx. 3 h). For this reason, monosodium L(+)-tartrate was non-toxic at 2.73 g/kg/day whereas monosodium DL-tartrate was toxic at this dosage.


Determination of herbicide residues in agricultural crops, foods, soil and water by chronometric method.
The method described is based on the biochemical detection of herbicides on a silica gel thin layer following their chromatographic separation. The detection reagent is a mixture of a homogenate of bean leaves (Phaseolus vulgaris) and of the redox indicator 2,6-dichloroindophenol. This chronometric determination of herbicide residues is based on the observation that dark blue inhibition zones appear on a pale yellow-green background during the exposure of the sprayed chromatoplates Silufol to light. The dark blue zones disappear again after a time, their lifetime is proportional to the amount of the herbicide in the zone. Because of the high selectivity and sensitivity of the biochemical detection this method does not require a multiple clean-up procedure, nor does it require sophisticated instrumentation. It equals gas chromatography in sensitivity and precision. The determination limit lies between 0.01 and 0.001 mg X kg-1, the average recovery rate is 85 to 90%.


Brain lectin-mediated agglutinability of dissociated cells from embryonic and postnatal mouse brain.
Brain extracts contain a soluble lectin which enables the agglutination of dissociated mouse brain cells via saccharidic receptors. The ability of the brain cells to be agglutinated depends on their stage of development in vivo. Furthermore, after birth, the mechanism of the lectin-promoted agglutination is complicated by the appearance of a self-aggregation of the dissociated cells. Lactose and galactosides are inhibitors of lectin-mediated agglutination as well as of the dissociated cells' self-aggregation.


Menthol facilitates dopamine-releasing effect of nicotine in rat nucleus accumbens.
Menthol is a significant flavoring additive in tobacco products. Accumulating clinical evidence suggests that menthol may promote tobacco smoking and nicotine dependence. Our previous studies demonstrated that menthol enhanced nicotine reinforcement in rats. However, it is unclear whether menthol interacts with nicotine at the neurochemical level. The present study used intracranial microdialysis to examine whether and the ways in which menthol affects nicotine-induced dopamine release in rats in the nucleus accumbens core (NAc), a terminal field of brain reward circuitry. To make comparisons with our previous work that showed an enhancing effect of menthol on nicotine self-administration behavior, male Sprague-Dawley rats were first trained in 20 daily 1-h sessions to press a lever for intravenous nicotine self-administration (15 μg/kg/infusion). Dopamine levels were then measured in the right NAc using intracranial microdialysis coupled with high-performance liquid chromatography. Five minutes before microdialysis, the rats received an intraperitoneal injection of menthol (0, 1, 2.5, and 5 mg/kg), a subcutaneous injection of nicotine (0.2 mg/kg or its vehicle), or both. Menthol alone did not affect dopamine levels in dialysates, whereas nicotine alone elevated dopamine levels. Combined nicotine and menthol administration significantly increased dopamine levels compared with nicotine alone. These data indicate a facilitating effect of menthol on nicotine-induced dopamine release in the NAc. These findings shed light on our understanding of the neurobiological mechanisms that underlie the menthol-induced enhancement of nicotine reinforcement.


COVID-19 and dengue co-infection in Brazil: optimal control and cost-effectiveness analysis.
A mathematical model for the co-interaction of COVID-19 and dengue transmission dynamics is formulated and analyzed. The sub-models are shown to be locally asymptotically stable when the respective reproduction numbers are below unity. Using available data sets, the model is fitted to the cumulative confirmed daily COVID-19 cases and deaths for Brazil (a country with high co-endemicity of both diseases) from February 1, 2021 to September 20, 2021. The fitting was done using the fmincon function in the Optimization Toolbox of MATLAB. Parameters denoting the COVID-19 contact rate, death rate and loss of infection acquired immunity to COVID-19 were estimated using the two data sets. The model is then extended to include optimal control strategies. The appropriate conditions for the existence of optimal control and the optimality system for the co-infection model are established using the Pontryagin's Principle. Different control strategies and their cost-effectiveness analyses were considered and simulated for the model, which include: controls against incident dengue and COVID-19 infections, control against co-infection with a second disease and treatment controls for both dengue and COVID-19. Highlights of the simulation results show that: (1) dengue prevention strategy could avert as much as 870,000 new COVID-19 infections; (2) dengue only control strategy or COVID-19 only control strategy significantly reduces new co-infection cases; (3) the strategy implementing control against incident dengue infection is the most cost-effective in controlling dengue and COVID-19 co-infections.


Accurate and precise plasma clearance measurement using four 99mTc-DTPA plasma samples over 4 h.
Glomerular filtration rate can be measured as the plasma clearance (CL) of a glomerular filtration rate marker despite body fluid disturbances using numerous, prolonged time samples. We desire a simplified technique without compromised accuracy and precision. We compared CL values derived from two plasma concentration curve area methods - (a) biexponential fitting [CL (E2)] and (b) Tikhonov adaptively regularized gamma variate fitting [CL (Tk-GV)] - for 4 versus 8 h time samplings from 412 Tc-DTPA studies in 142 patients, mostly paediatric patients, with suspected fluid disturbances. CL (Tk-GV) from four samples/4 h and from nine samples/8 h, both accurately and precisely agreed with the standard, which was taken to be nine samples/8 h CL from (noncompartmental) numerical integration [CL (NI)]. The E2 method, four samples/4 h, and nine samples/8 h median CL values significantly overestimated the CL (NI) values by 4.9 and 3.8%, respectively. Compared with the standard, CL (E2) from four samples/4 h and from nine samples/8 h proved to be the most inaccurate and imprecise method examined, and can be replaced by better methods for calculating CL. The CL (Tk-GV) can be used to reduce sampling time in half from 8 to 4 h and from nine to four samples for a precise and accurate, yet more easily tolerated and simplified test.


Cervical-transoral robotic nasopharyngectomy: A preclinical study.
We performed a preclinical study to assess the feasibility of the cervical-transoral robotic pharyngectomy procedure in surgery for nasopharyngeal cancer, where deep margins and vascular safety are key issues. Four cadaveric dissections were performed with the da Vinci Xi system. The first step was a robotic parapharyngeal dissection along the internal carotid artery (ICA). The second step was a type 3 transoral robotic nasopharyngectomy. In each procedure, a comprehensive dissection of the parapharyngeal space was performed along the ICA up to the foramen lacerum. A type 3 nasopharyngectomy was performed transorally with an "en-bloc" removal of the parapharyngeal space, and with complete removal of the eustachian tube up to its bony part. A comprehensive cervical-transoral robotic type 3 nasopharyngectomy with "en-bloc" removal of the parapharyngeal space and the eustachian tube proved to be technically feasible in a preclinical study.


Orthographic consistency affects spoken word recognition at different grain-sizes.
A number of previous studies found that the consistency of sound-to-spelling mappings (feedback consistency) affects spoken word recognition. In auditory lexical decision experiments, words that can only be spelled one way are recognized faster than words with multiple potential spellings. Previous studies demonstrated this by manipulating feedback consistency of rhymes. The present lexical decision study, done in English, manipulated the spelling of individual vowels within consistent rhymes. Participants recognized words with consistent rhymes where the vowel has the most typical spelling (e.g., lobe) faster than words with consistent rhymes where the vowel has a less typical spelling (e.g., loaf). The present study extends previous literature by showing that auditory word recognition is affected by orthographic regularities at different grain sizes, just like written word recognition and spelling. The theoretical and methodological implications for future research in spoken word recognition are discussed.


Anti-cancer efficiency of natural killer cells differentiated from human adipose tissue-derived mesenchymal stem cells and transfected with miRNA150.
The aim of this study is to investigate the effects of miR150 transfection on NK-like cells differentiated from adipose tissue derived mesenchymal stem cells (AD-MSCs). NK-like cells were differentiated from AD-MSCs and activated by miR150 transfection. Transfected/non-transfected NK-like cells were characterized by immunohistochemical and RT-PCR analyzes. Apoptotic efficiency of the transfected/non-transfected NK-like cells on pancreatic cancer cells PANC1 were determined by TUNEL and RT-PCR. In miR150-transfected cells, the increased expression of NK cell-specific genes such as GKMB, KIR2DL2, CD16, CD56, NKG2D, NKp46 and increased immunoreactivity of NK cell-specific surface marker CD314 (NKG2D) were evident. TUNEL assays showed that NK-like cells with/without transfection induced apoptosis in PANC1 cells in the same manner. The decrease in oncogene expression and the increase in the tumor suppressor gene expression in PANC1 cells upon co-culture with NK-like cells differentiated from AD-MSCs were more prominent following miRNA150 transfection. It was shown in vitro that NK-like cells could be obtained by differentiation from AD-MSCs and their efficiency could be increased via miR150 transfection. The results are encouraging for further clinical studies in improvement of immunotherapeutic approaches for cancer therapy.


[NMR imaging in the diagnosis of orbital fractures with loss of function].
According to the results of this study NMR imaging seems to be the method of choice in radiodiagnosis of orbital wall fractures for demonstrating impactions or prolapses of orbital contents. It is superior to classic radiography or computerized tomography.


Existence of two groups of Staphylococcus aureus strains isolated from bovine mastitis based on biofilm formation, intracellular survival, capsular profile and agr-typing.
Staphylococcus (S.) aureus is recognised worldwide as an important pathogen causing contagious acute and chronic bovine mastitis. Chronic mastitis account for a significant part of all bovine cases and represent an important economic problem for dairy producers. Several properties (biofilm formation, intracellular survival, capsular expression and group agr) are thought to be associated with this chronic status. In a previous study, we found the existence of two groups of strains based on the association of these features. The aim of the present work was to confirm on a large international and non-related collection of strains the existence of these clusters and to associate them with case history records. In addition, the genomes of eight strains were sequenced to study the genomic differences between strains of each cluster. The results confirmed the existence of both groups based on capsular typing, intracellular survival and agr-typing: strains cap8-positive, belonging to agr group II, showing a low invasion rate and strains cap5-positive, belonging to agr group I, showing a high invasion rate. None of the two clusters were associated with the chronic status of the cow. When comparing the genomes of strains belonging to both clusters, the genes specific to the group "cap5-agrI" would suggest that these strains are better adapted to live in hostile environment. The existence of these two groups is highly important as they may represent two clusters that are adapted differently to the host and/or the surrounding environment.


Sickle beta-thalassemia presenting as orbital compression syndrome.
Orbital compression syndrome is caused by disorders of varying etiologies involving the orbit and presents with ocular and extraocular dysfunction. Ocular involvement of sickle cell disease is uncommon. A 17-year-old male presented with low backache and proptosis of both eyes of 5 days duration without past history of pain crisis or transfusion. Examination revealed pallor, icterus, bilateral proptosis, conjuctival chemosis, and symmetrical restriction of ocular movements with preserved visual acuity. He was drowsy with no other focal deficits. The fundus showed macular edema, venous engorgement, and no hemorrhage. His peripheral smear showed presence of sickle cells. Computed tomography (CT) scan of the orbit revealed orbital subperiosteal hematomas. CT head images showed epidural hematoma in the frontal lobe. High-performance liquid chromatography (HPLC) and mutation studies revealed sickle beta-thalassemia in the patient. He was managed with supportive care, transfusions to keep hemoglobin above 10 g/dl, and hydroxyurea. The patient recovered fully and remained well during follow-up of 12 months. Our case was unique for presenting as orbital compression syndrome without any history of vaso-occlusive crisis.


Association of SULT1A2 rs1059491 with obesity and dyslipidaemia in southern Chinese adults.
In the sulfotransferase (SULT) superfamily, members of the SULT1 family mainly catalyse the sulfonation reaction of phenolic compounds, which is involved in the phase II metabolic detoxification process and plays a key role in endocrine homeostasis. A coding variant rs1059491 in the SULT1A2 gene has been reported to be associated with childhood obesity. This study aimed to investigate the association of rs1059491 with the risk of obesity and cardiometabolic abnormalities in adults. This case‒control study included 226 normal weight, 168 overweight and 72 obese adults who underwent a health examination in Taizhou, China. Genotyping of rs1059491 was performed by Sanger sequencing in exon 7 of the SULT1A2 coding region. Chi-squared tests, one-way ANOVA, and logistic regression models were applied. The minor allele frequencies of rs1059491 in the overweight combined with obesity and control groups were 0.0292 and 0.0686, respectively. No differences in weight and body mass index were detected between the TT genotype and GT + GG genotype under the dominant model, but the levels of serum triglycerides were significantly lower in G-allele carriers than in non-G-allele carriers (1.02 (0.74-1.32) vs. 1.35 (0.83-2.13) mmol/L, P = 0.011). The GT + GG genotype of rs1059491 versus the TT genotype reduced the risk of overweight and obesity by 54% (OR 0.46, 95% CI 0.22-0.96, P = 0.037) after adjusting for sex and age. Similar results were observed for hypertriglyceridaemia (OR 0.25, 95% CI 0.08-0.74, P = 0.013) and dyslipidaemia (OR 0.37, 95% CI 0.17-0.83, P = 0.015). However, these associations disappeared after correction for multiple tests. This study revealed that the coding variant rs1059491 is nominally associated with a decreased risk of obesity and dyslipidaemia in southern Chinese adults. The findings will be validated in larger studies including more detailed information on genetic background, lifestyle and weight change with age.


Cost-effectiveness of management strategies for patients with recurrent ovarian cancer and inoperable malignant bowel obstruction.
Patients with recurrent platinum-resistant ovarian cancer often present with inoperable malignant bowel obstruction (MBO) from a large burden of abdominal disease. Interventions such as total parenteral nutrition (TPN) and chemotherapy may be used in this setting. We aim to describe the relative cost-effectiveness of these interventions to inform clinical decision making. Four strategies for management of platinum-resistant recurrent ovarian cancer with inoperable MBO were compared from a societal perspective using a Monte Carlo simulation: (1) hospice, (2) TPN, (3) chemotherapy, and (4) TPN + chemotherapy. Survival, hospitalization rates, end-of-life (EOL) setting, and MBO-related utilities were obtained from literature review: hospice (survival 38 days, 6% hospitalization), chemotherapy (42 days, 29%), TPN (55 days, 25%), TPN + chemotherapy (74 days, 47%). Outcomes were the average cost per strategy and incremental cost-effectiveness ratios (ICERs) in US dollars per quality-adjusted life year (QALY) gained. In the base case scenario, TPN + chemotherapy was the most costly strategy (mean; 95% CI) ($49,741; $49,329-$50,162) and provided the highest QALYs (0.089; 0.089-0.090). The lowest cost strategy was hospice ($14,591; $14,527-$14,654). The TPN alone and chemotherapy alone strategies were dominated by a combination of hospice and TPN + chemotherapy. The ICER of TPN + chemotherapy was $918,538/QALY compared to hospice. With a societal willingness to pay threshold of $150,000/QALY, hospice was the strategy of choice in 71.6% of cases, chemotherapy alone in 28.4%, and TPN-containing strategies in 0%. TPN with or without chemotherapy is not cost-effective in management of inoperable malignant bowel obstruction and platinum-resistant ovarian cancer.


Cytotoxicity of 2-chlorodeoxyadenosine and arabinosylcytosine in leukaemic lymphoblasts from paediatric patients: significance of cellular nucleoside transporter content.
2-chlorodeoxyadenosine (2-CdA) and arabinosylcytosine (araC) are nucleoside drugs that are used to treat various leukaemias, although 2-CdA has not been tested extensively in children with acute lymphoblastic leukaemia (ALL). Nucleoside cytotoxicity depends on the conversion of these agents to 5'-phosphate derivatives, following drug entry into cells via nucleoside transport (NT) processes. This study compared es nucleoside transporter content, determined using a flow cytometric assay with SAENTA [5'-S-(2-aminoethyl)-N6-(4-nitrobenzyl)-5'-thioadenosine] fluorescein, and cytotoxicities of 2-CdA and araC in fresh lymphoblasts from previously untreated paediatric ALL patients and the human T-lymphoblast cell line, CCRF-CEM. Lymphoblast samples from individual patients ranged widely in sensitivity to both 2-CdA (IC50, 6 nmol/l to > 5 micromol/l; mean = 418 nmol/l; n = 8) and araC (IC50, 59 nmol/l to > 5 micromol/l; mean = 1050 nmol/l; n = 7), although IC50 values for the two drugs were correlated (r = 0.78, P = 0.032, n = 7). Cellular es nucleoside transporter content varied more than 35-fold among samples from 10 patients. The correlation between es nucleoside transporter content and drug sensitivity was statistically significant for araC (r = -0.93, P = 0.023, n = 5), but not for 2-CdA (r = -0.57, P = 0.23, n = 6). Exposure of CCRF-CEM cells to araC resulted in a substantial araC concentration-dependent increase in the relative survival of es transporter-deficient cells, whereas the increase was slight following exposure to 2-CdA. We conclude that, in ALL lymphoblasts, es nucleoside transporter content is a determinant of araC sensitivity and that a deficiency in NT may impart resistance to araC.


Long-term course of contrast sensitivity in eyes after laser-assisted in-situ keratomileusis for myopia.
To evaluate the long-term contrast sensitivity (CS) after laser in-situ keratomileusis (LASIK) for myopia. This retrospective, single-center, cohort study involved 190 eyes of 95 patients who underwent bilateral LASIK between January 2001 and October 2007. This study includes patients who underwent CS and higher-order aberration (HOA) measurements in a five-year postoperative period. For all enrolled patients, visual acuity, refractive error (RE) in diopters (D), CS at 3-, 6-, 12-, and 18-cycles per degree (cpd), and HOA in a 4 mm area of the dilated pupil were measured before surgery and 6 months, 1 year, and 5 years after it. The mean RE measured before the surgery and after 6 months, 1 year, and 5 years after was -6.08 ± 2.50D, -0.26 ± 0.65D, -0.28 ± 0.65D, and -0.48 ± 0.80D, respectively. There were no clinically significant changes between preoperative results and the measures taken 6 months, 1 year, and 5 years after surgery. The slight increase in HOA had little effect on CS over the mid to long-term postoperative period. Our findings show that CS does not clinically change post LASIK. Although we were unable to identify the specific mechanism, we theorize that after LASIK there is a possibility for the compensation of HOA.


The hemostatic properties of transurethral plasmakinetic resection of the prostate: comparison with conventional resectoscope in an ex vivo study.
To compare the hemostatic properties of transurethral plasmakinetic resection of the prostate (PKRP) and standard transurethral resection of the prostate (TURP) ex vivo, as perioperative bleeding is still regarded as one of the major complications of transurethral prostatectomy. Isolated normal saline (NS)-perfused porcine kidneys were used to determine the hemostatic efficacy of PKRP and TURP. The perfusion fluid loss was semiquantitatively measured in relation to tissue ablation for the two techniques and specimens were evaluated histologically. The PKRP group had a significantly smaller loss of NS than the TURP group (4.16 +/- 1.25 and 6.39 +/- 1.05 g/min, respectively, p < 0.01). Compared with the measurements with TURP, the depths of the coagulation zones with PKRP were significantly larger (225.09 +/- 35.77 and 146.84 +/- 18.91 microm, respectively, p< 0.01). PKRP ex vivo was associated with significantly better hemostasis than TURP.


Vaccination strategies for lymphomas.
Vaccination strategies for lymphomas were developed along with one of the first recognized tumor-specific targets, the clonal antigen receptor, composed of unique variable regions known as idiotypes. Human clinical trials of idiotype vaccination have benefited from highly concordant animal models, leading to sequential improvements in design. Evidence of the clinical benefit of idiotype vaccines is strong but formally unproven. Significant progress has been made in our understanding of the basic mechanisms underlying the induction of immune responses, which has led to a proliferation of rationally designed immunotherapeutic strategies. Current research efforts include the development of more convenient methods to produce individual idiotype vaccines, the establishment of definitive proof for clinical efficacy, and the implementation of alternative vaccination strategies, including genetic vaccination and genetically or immunologically modified autologous tumor cells and dendritic cells.


Sneddon's syndrome. A case report.
This report reviews the case of a young woman who has livedo reticularis and cerebrovascular disease. A skin biopsy specimen taken from normal skin showed endarteritis obliterans. This finding, in combination with the clinical findings, confirmed the diagnosis of Sneddon's syndrome.


Costs of parental care in the gastropod Conus pennaceus: Age-specific changes and physical constraints.
Age-specific changes in the allocation of reproductive energy to protective capsules, ova and intracapsular fluid are documented for the marine gastropod Conus pennaceus. As female snails grow in shell length they produce larger capsules with thicker and stronger walls. Because large capsules contain lower densities of ova than do small ones, growing females must increase the number, as well as the size, of egg capsules they produce. As a result of this pattern of ova packaging, per ovum costs of encapsulation (parental care) increase with increasing female size and age. The data suggest that the number of embryos a capusle can support may be limited by respiratory constraints related to capsule surface area or wall thickness. As capsule size increases, surface/volume ratios decline and capsule wall thickness increases. Either of these processes should result in a reduction in net gas transport per unit of capsule contents.


Thyroid hemorrhage causing airway obstruction after intravenous thrombolysis for acute ischemic stroke.
There are several life-threatening complications associated with intravenous thrombolysis after acute ischemic stroke such as symptomatic intracerebral hemorrhage, orolingual angioedema, or less frequent, bleedings of the mucosa or ecchymosis. Aside from these known critical incidents, rare and unfamiliar complications may be even more challenging, as they are unexpected and may mimic events that appear more frequently. We report a rare and unusual acute complication of intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA) (0.9 mg/kg) administered for acute ischemic stroke. Medical records, radiologic imaging, and pathologic specimens were reviewed. A 86-year-old woman developed acute respiratory failure 20 h after thrombolysis with suspected angioedema triggered by intravenous rt-PA. The inspiratory stridor and dyspnea were unresponsive to bronchodilators, corticosteroids, and inhaled adrenaline. After endotracheal intubation, laryngoscopy showed no significant supraglottic narrowing. Thyroidal sonography and cervical computed tomography revealed a thyroidal mass causing a tracheal and vascular compression compatible with thyroidal hemorrhage. Sonography showed a nodular goiter of the right thyroid gland. A total thyroidectomy was performed and histologic analysis confirmed a hemorrhage of the right thyroidal lobe. Acute airway obstruction with respiratory failure due to thyroidal hemorrhage after intravenous thrombolysis is an important life-threatening complication, mimicking an anaphylactic reaction or a more frequent orolingual angioedema.